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MS22100	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE A limited number of clinical trials have shown that the total contact cast ( TCC ) is an effective treatment in neuropathic , noninfected , and nonischemic foot ulcers . In this prospect i ve data collection study , we assessed outcome and complications of TCC treatment in neuropathic patients with and without peripheral arterial disease ( PAD ) or ( superficial ) infection . RESEARCH DESIGN AND METHODS Ninety-eight consecutive patients selected for casting were followed until healing ; all had polyneuropathy , 44 % had PAD , and 29 % had infection . Primary outcomes were percentage healed with a cast , time to heal , and number of complications . RESULTS Ninety percent of all nonischemic ulcers without infection and 87 % with infection healed in the cast ( NS ) . In patients with PAD but without critical limb ischemia , 69 % of the ulcers without infection and 36 % with infection healed ( P < 0.01 ) . In multivariate analyses , PAD , infection , and heel ulcers were associated with a lower percentage healed ( all P < 0.05 ) . Median duration of cast treatment was 34 days . New ulcers , all superficial , developed in 9 % and preulcerative lesions in 28 % of the patients ; these skin lesions healed in the cast within a maximum of 13 days . CONCLUSIONS In comparison to pure neuropathic ulcers , ulcers with moderate ischemia or infection can be treated effectively with casting . However , when both PAD and infection are present or the patient has a heel ulcer , outcome is poor and alternative strategies should be sought . The high rate of preulcerative lesions stresses the importance of close monitoring during TCC treatment OBJECTIVE The purpose of this study was to compare the effectiveness of a removable cast walker ( RCW ) rendered irremovable ( iTCC ) with the total contact cast ( TCC ) in the treatment of diabetic neuropathic plantar foot ulcers . RESEARCH DESIGN AND METHODS In a prospect i ve , r and omized , controlled trial , 41 consecutive diabetic patients with chronic , nonischemic , neuropathic plantar foot ulcers were r and omly assigned to one of two groups : a RCW rendered irremovable by wrapping it with a single layer of fiberglass casting material ( i.e. , an iTCC ) or a st and ard TCC . Primary outcome measures were the proportion of patients with ulcers that healed at < /=12 weeks , healing rates , complication rates , cast placement/removal times , and costs . RESULTS The proportions of patients with ulcers that healed within 12 weeks in the iTCC and TCC groups were 80 and 74 % , respectively ( 94 and 93 % , respectively , when patients who were lost to follow-up were excluded ) . Survival analysis ( healing rates ) was statistically equivalent in the two groups , as were complication rates , but with a trend toward benefit in the iTCC group . The iTCC took significantly less time to place and remove than the TCC with 39 % and 36 % reductions , respectively . There was also an overall lower cost associated with the use of the iTCC compared with the TCC . CONCLUSIONS The iTCC may be equally efficacious , faster to place , easier to use , and less expensive than the TCC in the treatment of diabetic plantar neuropathic foot ulcers Neuropathic plantar ulcers are classical lesions secondary to diabetic polyneuropathy ( 1,2 ) . The worldwide gold st and ard treatment is the nonremovable off-loading cast ( 3–5 ) . However , the device is not widely used due to concerns related to risk factors of the off-loading cast ( i.e. , joint rigidity , additional ulcer formation beneath the cast , and infection of the ulcer enclosed in the cast ) . Our group recently demonstrated that it is possible to reduce the risk of side effects reported in literature by constructing the off-loading cast using fiberglass b and ages of different rigidity . Considering the device ’s scarce application because of the side effects , we conducted a controlled , r and omized , prospect i ve trial to evaluate the safety and efficacy of a removable pneumatic cast walker in comparison with a nonremovable fiberglass off-loading cast . Between January 2005 and October 2005 , 60 consecutive diabetic patients with neuropathic plantar ulcers were seen and r and omly assigned to two groups : group A , using an Aircast Pneumatic Walker ( XP Diabetic Walker ) ; and group B , using the fiberglass off-loading cast . All participants had peripheral neuropathy , as highlighted by insensitivity to 10 g monofilament and vibration perception threshold measured by biothesiometer at malleolus of at least 25 volts , and presented OBJECTIVE —This study was design ed to test the safety , effectiveness , and costs of off-loading with a novel , off-the-shelf irremovable device in the management of diabetic foot ulceration ( DFU ) . RESEARCH DESIGN AND METHODS —We prospect ively evaluated off-loading of neuropathic plantar ulcers in 40 diabetic out patients attending our diabetic foot clinic and compared healing rates at the 12-week follow-up , number and severity of adverse events , healing time , costs and applicability of the device , and patients ’ satisfaction between those r and omly assigned to total contact casting ( TCC ; group A ) or to the Optima Diab walker ( group B ) . Deep or infected ulcers were excluded . RESULTS —No difference between groups A and B was observed in healing rates at 12 weeks ( 95 vs. 85 % ) , healing time ( 6.5 ± 4.4 vs. 6.7 ± 3.4 weeks ) , and number of adverse events ( six versus four ) . Treatment was significantly less expensive in group B , which showed a mean reduction of costs of 78 % compared with group A ( P < 0.001 ) . Practicability was more favorable in group B , with a reduction of 77 and 58 % of the time required for application and removal of the devices , respectively ( P < 0.001 ) . Patients ’ satisfaction with the treatment was higher in group B ( P < 0.01 ) . CONCLUSIONS —The Optima Diab walker is as safe and effective as TCC in the management of DFU , but its lower costs and better applicability may be of help in spreading the practice of off-loading among the centers that manage the diabetic foot OBJECTIVE To compare the efficacy , safety , and compliance of a nonremovable fiberglass cast boot and off-loading shoes in the treatment of diabetic plantar ulcers . RESEARCH DESIGN AND METHODS Patients ( n = 93 ) with noninfected , nonischemic plantar ulcers were included in this prospect i ve nonr and omized study . Treatment used a nonremovable fiberglass cast boot for longer st and ing and deeper ulcers ( n = 42 ) and a half shoe or heel-relief shoe for other ulcers ( n = 51 ) . We evaluated off-loading therapy , compliance , and complications in both groups . RESULTS The healing rate was significantly higher with the cast boot than with the off-loading shoe ( 81 vs. 70 % , P = 0.017 ) , with healing times of 68.6 + /- 35.1 vs. 134.2 + /- 133.0 days , respectively , and hazard ratio 1.68 ( 95 % CI 1.04 - 2.70 ) ; complete compliance with treatment was 98 vs. 10 % ( P = 0.001 ) , respectively . Secondary osteomyelitis developed in 3 patients in the cast boot group and 13 patients in the off-loading shoe group ( P = 0.026 ) . CONCLUSIONS A nonremovable fiberglass cast boot was effective in healing diabetic plantar ulcers and in decreasing the risk of secondary osteomyelitis . The cast boot forced compliance with off-loading , thus promoting healing OBJECTIVE To evaluate the efficacy of a removable cast walker compared with that of a nonremovable fiberglass off-bearing cast in the treatment of diabetic plantar foot ulcer . RESEARCH DESIGN AND METHODS Forty-five adult diabetic patients with nonischemic , noninfected neuropathic plantar ulcer were r and omly assigned for treatment with a nonremovable fiberglass off-bearing cast ( total contact cast [ TCC ] group ) or walker cast ( Stabil-D group ) . Treatment duration was 90 days . Percent reduction in ulcer surface area and total healing rates were evaluated after treatment . RESULTS A total of 48 patients were screened ; however , 2 patients in the TCC group and 1 patient in the Stabil-D group did not complete the study and were considered dropouts . There were no significant differences in demographic and clinic characteristics of the 45 patients completing the study . Ulcer surface decreased from 1.41 to 0.21 cm2 ( P < 0.001 ) in the TCC group and from 2.18 to 0.45 cm2 ( P < 0.001 ) in the Stabil-D group , with no significant differences between groups ( P = 0.722 ) . Seventeen patients ( 73.9 % ) in the TCC group and 16 patients ( 72.7 % ) in the Stabil-D group achieved healing ( P = 0.794 ) . Average healing time was 35.3 ± 3.1 and 39.7 ± 4.2 days in the TCC and Stabil-D group , respectively ( P = 0.708 ) . CONCLUSIONS The Stabil-D cast walker , although removable , was equivalent in efficacy to the TCC in terms of ulcer size reduction and total healing rate . The easier use of Stabil-D may help increase the use of off-loading devices in the management of plantar neuropathic diabetic foot ulcers The objective of this study was to compare the effectiveness of irremovable total-contact casts ( TCC ) and custom-made temporary footwear ( CTF ) to heal neuropathic foot ulcerations in individuals with diabetes . In this prospect i ve clinical trial , 43 patients with plantar ulcer Grade 1 or 2 ( Wagner scale ) were r and omized to one of two off-loading modalities : TCC or CTF . Outcomes assessed were wound surface area reduction ( cm2 ) and time to wound healing ( days ) at 2 , 4 , 8 and 16 weeks . To evaluate safety , possible side effects were recorded at each follow-up visit . The results showed no significant difference in wound surface area reduction ( adjusted for baseline wound surface ) at 2 , 4 , 8 or 16 weeks ( adjusted mean difference 0.10 cm2 ; 95 % CI −0.92−0.72 at 16 weeks ) . At 16 weeks , 12 patients had a completely healed ulcer , 6 per group . The median time to healing was shorter for the patients using a cast ( 52 vs. 90 days , p = 0.26 ) . Five patients with TCC and two with CTF developed device-related complications . It was concluded that : ( i ) the rate of wound healing is not significantly different for patients treated with CTF or TCC . The difference in wound surface area was small and not significant at any time during follow-up ; and ( ii ) the difference in healing time ( 38 days ) may have attained statistical significance if the numbers in these sub-groups ( 2 × 6 ) had been higher . Since there appears to be little difference in effectiveness between both off-loading modalities , further investigation into the benefits of CTF is warranted OBJECTIVE The purpose of this study was to evaluate the effectiveness of a removable cast walker ( RCW ) and an " instant " total contact cast ( iTCC ) in healing neuropathic diabetic foot ulcerations . RESEARCH DESIGN AND METHODS We r and omly assigned 50 patients with University of Texas grade 1A diabetic foot ulcerations into one of two off-loading treatment groups : an RCW or the same RCW wrapped with a cohesive b and age ( iTCC ) so patients could not easily remove the device . Subjects were evaluated weekly for 12 weeks or until wound healing . RESULTS An intent-to-treat analysis showed that a higher proportion of patients had ulcers that were healed at 12 weeks in the iTCC group than in the RCW group ( 82.6 vs. 51.9 % , P = 0.02 , odds ratio 1.8 [ 95 % CI 1.1 - 2.9 ] ) . Of the patients with ulcers that healed , those treated with an iTCC healed significantly sooner ( 41.6 + /- 18.7 vs. 58.0 + /- 15.2 days , P = 0.02 ) . CONCLUSIONS Modification of a st and ard RCW to increase patient adherence to pressure off-loading may increase both the proportion of ulcers that heal and the rate of healing of diabetic neuropathic wounds OBJECTIVE To compare the effectiveness of total contact casts , commercially available therapeutic shoes , and removable walking casts to reduce mean peak plantar foot pressures at the site of neuropathic ulcerations in diabetic subjects . RESEARCH DESIGN AND METHODS We compared the reduction in peak plantar pressures at ulcer sites under the great toe ( n = 5 ) , first metatarsal ( n = 10 ) , and second through fifth metatarsals ( n = 10 ) using six treatments : total contact casts ( TCCs ) , DH Pressure Relief Walkers ( DH ) , Aircast Pneumatic Walkers , Three D Dura-Steppers ( 3D ) , CAM Walkers , and P.W. Minor Xtra Depth shoes . A rubber sole canvas oxford was used to establish Output:	In conclusion , non-removable off-loading devices regardless of type , are more likely to result in ulcer healing than removable off-loading devices , presumably because patient compliance with off-loading is facilitated
MS22101	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The Trial of Antihypertensive Interventions and Management is a multicenter r and omized trial design ed to examine the diastolic blood pressure response of various combinations of pharmacological and dietary interventions in the treatment of mild hypertension ( diastolic blood pressure 90 - 100 mm Hg ) . Eight hundred and seventy-eight participants at 110 - 160 % of ideal weight were r and omly allocated to nine drug/diet treatment groups receiving either a placebo , chlorthalidone ( 25 mg ) , or atenolol ( 50 mg ) , combined with a usual , a weight loss , or a low sodium/high potassium diet The primary outcome was diastolic blood pressure change from baseline to 6 months . Seven hundred and eighty-seven participants had follow-up data . The mean baseline diastolic blood pressure was 93.8 mm Hg ; 55.9 % of the participants were male , and the weight loss diet group lost an average of 4.7 kg . Multiple comparisons were accounted for in the analysis . A significantly greater lowering of diastolic blood pressure ( 12.4 mm Hg ) was achieved in the atenolol group compared with either the low sodium/high potassium diet group ( 7.9 mm Hg , p=0.001 ) or weight loss group ( 8.8 mm Hg , p=0.006 ) . Adding weight loss to chlorthalidone significantly enhanced blood pressure lowering ( 15.1 mm Hg ) when compared with the diuretic alone ( 10.8 mm Hg , p=0.002 ) , but adding a low sodium/high potassium diet ( 12.2 mm Hg , p=0.029 ) did not In the short-term treatment of mild hypertension where diastolic blood pressure is the sole consideration , drugs outperform diet , and weight loss is beneficial , especially with diuretics OBJECTIVE To determine whether an increase in dietary potassium intake from natural foods reduces the need for antihypertensive medication in patients with essential hypertension . DESIGN R and omized , controlled trial with 1-year follow-up . SETTING Hypertension outpatient clinic of a university hospital . PATIENTS Fifty-four patients with well-controlled hypertension , 47 of whom completed 1 year of follow-up . INTERVENTION Patients were r and omly assigned to one of two groups and were given dietary advice aim ed at selectively increasing potassium intake ( group 1 ) or at keeping their customary diet unchanged ( group 2 ) . During a 1-year follow-up period , drug therapy was reduced in stepwise fashion , according to a fixed protocol , provided that blood pressure remained below 160/95 mm Hg . MAIN RESULTS Potassium intake was checked monthly by referring to 3-day food records and by measuring 24-hour urinary potassium excretion . Potassium intake increased in group 1 but did not change in group 2 ( P less than 0.001 ) . No change was observed in either urinary sodium excretion or in body weight . After 1 year , the average drug consumption ( number of pills per day ) relative to that at baseline was 24 % in group 1 ( 95 % Cl , 15 % to 32 % ) and 60 % in group 2 ( Cl , 44 % to 76 % ) ( P less than 0.001 ) . By the end of the study , blood pressure could be controlled using less than 50 % of the initial therapy in 81 % of the patients in group 1 ( Cl , 66 % to 96 % ) compared with 29 % of the patients in group 2 ( Cl , 10 % to 48 % ) ( P = 0.001 ) . Patients in group 1 ended the study with a lower number of reported symptoms compared with patients in the control group ( P less than 0.001 ) . CONCLUSION Increasing the dietary potassium intake from natural foods is a feasible and effective measure to reduce antihypertensive drug treatment Phase I of the Trials of Hypertension Prevention ( TOHP ) was a r and omized , multicenter investigation that included double-blind , placebo-controlled testing of calcium and magnesium supplementation among 698 healthy adults ( 10.5 % blacks and 31 % women ) aged 30 to 54 years with high-normal diastolic blood pressure ( DBP ) ( 80 to 89 mm Hg ) . Very high compliance ( 94 to 96 % by pill counts ) with daily doses of 1 g of calcium ( carbonate ) , 360 mg of magnesium ( diglycine ) , or placebos was corroborated for the active supplements by significant net increases in all urine and serum compliance measures in white men and for urine compliance measures in white women . Overall , neither calcium nor magnesium produced significant changes in blood pressure at 3 and 6 months . Analyses stratified by baseline intakes of calcium , magnesium , sodium , or initial blood pressures also showed no effect of supplementation . These analyses suggested that calcium supplementation may have result ed in a DBP decrease in white women and that response modifiers in this subgroup might have included lower initial urinary calcium levels , urinary sodium levels , or lower body mass index . However , overall analyses indicated that calcium and magnesium supplements are unlikely to lower blood pressure in adults with high-normal DBP . The subgroup analyses , useful to formulate hypotheses , raise the possibility of a benefit to white women , which requires testing in future trials Thirty-three patients with hypertension receiving drug treatment that included a potassium losing diuretic were r and omly allocated to 64 mmol of potassium ( 14 patients ) or to no additional potassium supplementation ( 19 patients ) . Potassium was administered as slow release potassium chloride . After 3 months , blood pressure fell by 5/1 mm Hg in the patients who received the supplements and by 7/4 mm Hg in those who did not receive them . The falls in pressure were not significantly different and the 90 % confidence limits for the effect of supplementation on diastolic pressure were : a fall of 2 mm Hg and a rise of 11 mm Hg , thus excluding an important hypotensive effect in these patients . Conversely , plasma creatinine fell by 11 % in the supplement group compared with a 6 % rise in the control group ( P less than 0.05 ) . Potassium supplementation , either by pharmacological preparations or by dietary manipulation , may prove to be desirable in patients on a potassium losing diuretic but should not be expected to lower blood pressure in such patients Potassium chloride ( KCl ) salt ( 65 mmol ) daily reduced BP from 153/104 to 146/101 mmHg in 32 hypertensive black females during a 6-week placebo controlled crossover study . The fall in BP was independent of the order of r and omization and was significant for systolic ( SBP ; P less than 0.01 ) and diastolic ( DBP ; P less than 0.05 ) pressure after 4 weeks . Analysis of the 95 % confidence intervals in this and in five other studies , two of which were reported as showing no beneficial effect , suggests that potassium supplementation does lower BP , but that the change is small and within the confidence levels of all six trials . Thus , apparent discrepancies in the literature are not genuine statistically The blood pressure responses of 19 mildly hypertensive ( diastolic blood pressure 90–104 mmHg ) individuals to treatment with either 1200 mg of elemental calcium supplementation or placebo were assessed weekly in a 6-month r and omized , double-blind , placebo-controlled crossover study . Both groups showed a decrease in blood pressure ( calcium treated : 6 ± 12 mmHg systolic , 7 ± 7 mmHg diastolic ; and placebo controlled : 9 ± 14 mmHg systolic , 9 ± 8 mmHg diastolic ) . Differences between the two groups were not significant ( P > 0.1 ) . There were no adverse effects to either treatment . This study does not support the hypothesis that dietary calcium supplementation is more effective than placebo in reducing blood pressure in mildly hypertensive individuals In a double-blind , placebo-controlled trial with 58 normotensive female students , the effect of oral-calcium supplementation ( 1500 mg Ca++/day for 6 wk ) on diastolic and systolic blood pressure was studied while students were consuming a low-calcium diet ( 500 mg Ca++/day ) by restricting the intake of dairy products . Results show that , in both the calcium- and placebo-supplemented groups , blood pressure values decreased slightly and no effect of oral-calcium supplementation on blood pressure could be demonstrated . In addition , at baseline neither systolic nor diastolic blood pressure correlated with habitual calcium intake . Diastolic but not systolic blood pressure correlated significantly with body mass index ( r = 0.31 , p = 0.01 ) . It is concluded that oral-calcium supplementation for 6 wk does not influence blood pressure in young , healthy normotensive females consuming low-calcium diet BACKGROUND Total body potassium ( TBK ) is an index of fat-free mass . Data describing changes in TBK in African American , Asian , or Hispanic population s have not been reported . OBJECTIVE The aim was to investigate possible sex and racial differences in TBK in adults over an age range of 70 y. DESIGN The study used longitudinal and cross-sectional data collected in a body-composition unit from 973 men and 1368 women of African American , Asian , white , and Hispanic race-ethnicity . R and om coefficient models in which baseline weight and height were taken into account were applied to estimate sex-specific changes in TBK among the 4 racial-ethnic groups . RESULTS The ages of 30 and 31 y were identified for women and men , respectively , as the cutoffs after which TBK began to decline . Both sexes had similar racial-ethnic patterns for expected mean TBK at the age cutoffs : African Americans had the highest value , followed by whites , Hispanics , and Asians . After the age cutoffs , the decline in TBK differed by race and sex . In women , African Americans showed the most rapid decline , whereas Asians had the lowest . In men , Hispanics had the most rapid decline in TBK , followed by African Americans , whites , and Asians . CONCLUSION Significant sex and racial differences exist in the rate of change in TBK with age . Further studies are needed to explore the associations of declining TBK with health risks OBJECTIVE To determine the effect of potassium supplementation on blood pressure in African Americans consuming a low-potassium diet . DESIGN R and omized , double-blind , placebo-controlled trial with two parallel arms . SETTING Community-based research site . PARTICIPANTS Eighty-seven healthy African Americans aged 27 to 65 years with a systolic blood pressure between 100 and 159 mm Hg and a diastolic blood pressure between 70 and 94 mm Hg . INTERVENTION During the 21-day intervention period , all participants were provided with a low-potassium diet ( 32 to 35 mmol/d ) . In addition to this diet , they were r and omly assigned to receive either potassium supplements ( 80 mmol/d ) or placebo . MAIN OUTCOME MEASURE Change in blood pressure in the potassium vs the placebo group , based on a total of nine blood pressure readings at three visits . Blood pressures were taken before and during the intervention by means of r and om-zero sphygmomanometry . RESULTS At baseline , the placebo and potassium groups were similar for mean blood pressure ( 127/78 vs 125/77 mm Hg ) , 24-hour urinary potassium excretion ( 50 vs 44 mmol ) , and all other variables measured ( all P > .05 ) . During the intervention , the net difference in 24-hour urinary potassium excretion between groups was 70 mmol . Compared with the placebo group , the potassium supplementation group experienced a net decline in systolic blood pressure of 6.9 mm Hg ( 95 % confidence interval , -9.3 to -4.4 mm Hg ; P < .001 ) and a decline in diastolic blood pressure of 2.5 mm Hg ( 95 % confidence interval , -4.3 to -0.8 mm Hg ; P = .004 ) . Simultaneous adjustment for differences in baseline characteristics only strengthened these estimates . CONCLUSIONS Potassium supplementation reduces blood pressure substantially in African Americans consuming a diet low in potassium . Increased potassium intake may play an important role in reducing blood pressure in this population at high risk for hypertension Epidemiological and experimental data suggest blood pressure-lowering effects of dietary potassium . A r and omized , double-blind clinical trial was used to assess blood pressure response to orally administered potassium , 120 mEq/day , and to placebo in 101 adults with mild hypertension . Blood pressure was measured with a r and om-zero sphygmomanometer every 2 weeks of this 8-week trial . Systolic blood pressure in the potassium-treated group decreased by 6.4 + /- 13.7 ( SD ) mm Hg ( p less than or equal to 0.025 ) compared with 0.11 + /- 13.0 mm Hg in the placebo-treated group ( p = 0.96 ) . Diastolic blood pressure in the pot Output:	The substantial heterogeneity between trials was not explained by potassium dose , quality of trials or baseline blood pressure . This systematic review found no statistically significant effect of potassium supplementation on blood pressure .
MS22102	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Delirium occurs commonly among older hospitalized patients and is frequently not recognized . In an effort to identify tools useful to clinicians in the diagnosis of delirium , test characteristics of four screening instruments were compared . METHODS Patients 65 years of age or older who were admitted to one of four medical and surgical wards of a university teaching hospital were followed up prospect ively . Potential subjects were excluded if unavailable for interviews or discharged within 48 hours of admission , or if judged too impaired to participate in the daily interviews . Research assistants administered four instruments used to detect delirium : Digit Span Test , Vigilance ' A ' Test , Clinical Assessment of Confusion , and Confusion Assessment Method . Abnormal scores on these tests or suspicion of acute confusion prompted a referral to the clinician-investigators who then assessed the patient daily for delirium based on the Diagnostic and Statistical Manual of Mental Disorders , Revised Third Edition criteria . RESULTS Delirium occurred in 64 ( 14.8 % ) of 432 subjects . The positive likelihood ratios for all of the instruments were significantly more than 1 . The instruments remained useful when applied to selected subgroups : subjects in whom acute mental status changes were documented , subjects on surgical services , and subjects with impaired cognitive status on admission . Combinations of any two instruments did not perform substantially better than the instrument with the best test characteristics : the Clinical Assessment of Confusion . All instruments were more useful at confirming delirium than in excluding it . CONCLUSION The four instruments studied , which are suitable for use at the bedside , can aid the clinician in identifying patients likely to be suffering from delirium OBJECTIVES This paper aim ed to measure the prevalence and outcomes of delirium for patients over 70 admitted to a general hospital for acute medical care and to assess the validity of the Delirium Rating Scale-Revised-98 ( DRS-R-98 ) in this setting . METHODS Prospect i ve study in a British acute general hospital providing sole emergency medical services for its locality . We screened consecutive patients over 70 with an unplanned emergency hospital admission and recruited a cohort of 249 patients likely to have mental health problems . They were assessed for health status at baseline and followed over 6 months . A sub- sample of 93 participants was assessed clinical ly for delirium . RESULTS 27 % ( 95 % confidence interval ( CI ) 23 - 31 ) of all older medical patients admitted to hospital had DRS-diagnosed delirium , and 41 % ( 95 % CI 37 - 45 ) had dementia ( including 19 % with co-morbid delirium and dementia ) . Compared with clinician diagnosis , DRS-R-98 sensitivity was at least 0.75 , specificity 0.71 . Compared with reversible cognitive impairment , sensitivity was at least 0.50 , specificity 0.67 . DRS-diagnosed delirium was associated with cognitive impairment , mood , behavioural and psychological symptoms , activities of daily living , and number of drugs prescribed , supporting construct validity . Of those with DRS-diagnosed delirium , 37 % died within 6 months ( relative risk 1.4 , 95 % CI 0.97 - 2.2 ) , 43 % had reversible cognitive impairment , but only 25 % had clinical ly important recovery in activities of daily living . Behavioural and psychological symptoms were common and mostly resolved , but new symptoms frequently developed . CONCLUSION Delirium is common . Some , but not all , features are reversible . DRS-R-98 has reasonable validity in population s where co-morbid dementia is prevalent OBJECTIVE To develop and vali date a new st and ardized confusion assessment method ( CAM ) that enables nonpsychiatric clinicians to detect delirium quickly in high-risk setting s. DESIGN Prospect i ve validation study . SETTING Conducted in general medicine wards and in an outpatient geriatric assessment center at Yale University ( site 1 ) and in general medicine wards at the University of Chicago ( site 2 ) . PATIENTS The study included 56 subjects , ranging in age from 65 to 98 years . At site 1 , 10 patients with and 20 without delirium participated ; at site 2 , 16 patients with and 10 without delirium participated . MEASUREMENTS AND MAIN RESULTS An expert panel developed the CAM through a consensus building process . The CAM instrument , which can be completed in less than 5 minutes , consists of nine operationalized criteria from the Diagnostic and Statistical Manual of Mental Disorders ( DSM-III-R ) . An a priori hypothesis was established for the diagnostic value of four criteria : acute onset and fluctuating course , inattention , disorganized thinking , and altered level of consciousness . The CAM algorithm for diagnosis of delirium required the presence of both the first and the second criteria and of either the third or the fourth criterion . At both sites , the diagnoses made by the CAM were concurrently vali date d against the diagnoses made by psychiatrists . At sites 1 and 2 values for sensitivity were 100 % and 94 % , respectively ; values for specificity were 95 % and 90 % ; values for positive predictive accuracy were 91 % and 94 % ; and values for negative predictive accuracy were 100 % and 90 % . The CAM algorithm had the highest predictive accuracy for all possible combinations of the nine features of delirium . The CAM was shown to have convergent agreement with four other mental status tests , including the Mini-Mental State Examination . The interobserver reliability of the CAM was high ( kappa = 0.81 - 1.0 ) . CONCLUSIONS The CAM is sensitive , specific , reliable , and easy to use for identification of delirium Background : Major depression is a frequent and serious disorder in older medical in patients . Because the condition goes undetected and untreated in most of these patients , we conducted a r and omized clinical trial to evaluate the effectiveness of a strategy of systematic detection and multidisciplinary treatment of depression in this population . Methods : Consecutive patients aged 65 years or more admitted to general medical services in a primary care hospital between October 1999 and November 2002 were screened for depression with the Diagnostic Interview Schedule ( DIS ) within 48 hours after admission . Patients found to have major depression were r and omly allocated to receive the intervention or usual care . The intervention involved consultation and treatment by a psychiatrist and follow-up by a research nurse and the patient 's family physician . Research assistants , blind to group allocation , collected data from the patients at enrolment and at 3 and 6 months later using the Hamilton Depression Rating Scale ( HAMD ) , the Medical Outcomes 36-item Short Form ( SF-36 ) , the DIS , the Mini-Mental State Examination ( MMSE ) , the Older Americans Re sources and Services ( OARS ) question naire to assess basic and instrumental activities of daily living ( OARS-ADL and OARS-IADL ) and the Rating Scale for Side Effects . Data on the severity of illness , length of hospital stay , health services and medication use , mortality and process of care were also collected . The primary outcome measures were the HAMD and SF-36 . Results : Of 1500 eligible patients who were screened , 157 were found to have major depression and consented to participate ( 78 in the intervention group and 79 in the usual care group ) . At r and omization , there were no clinical ly or statistically significant differences between the 2 groups . Sixty-four patients completed follow-up to 6 months , 57 withdrew , and 36 died . At 6 months , there were no clinical ly or statistically significant differences the 2 groups in HAMD or SF-36 scores or any of the secondary outcome measures . Interpretation : We were unable to demonstrate that systematic detection and multidisciplinary care of depression was more beneficial than usual care for elderly medical in patients Delirium is a common neuropsychiatric complication in patients with advanced cancer . The Memorial Delirium Assessment Scale ( MDAS ) is a recently developed 10‐item severity rating instrument . The purpose of the current prospect i ve study was to further assess the clinical utility , factor structure , and validity of the MDAS in a relatively homogeneous population of patients with advanced cancer The purpose of this study undertaken in an acute care hospital was to evaluate sensitivity and specificity of the documentation of nurse-reported delirium symptoms in medical charts . This is a descriptive study based on the clinical assessment s of a study nurse and nursing notes in the medical charts of 226 delirious older patients newly admitted to an acute care hospital . The results of this prospect i ve validation study indicated that documentation of delirium symptoms is poor . Disorientation , agitation and altered level of consciousness were the three symptoms yielding a higher level of sensitivity , but even so said symptoms were reported in less than a third of the medical charts . Univariate analysis suggested that higher comorbidity level , more severe symptoms of delirium and the use of physical restraints were associated with more valid documentation of delirium symptoms in medical charts . Lastly , this study corroborates results of previous studies , indicating that documentation of delirium symptoms in medical charts can be improved . Future study should target improving nurse documentation of delirium symptoms in medical charts very elderly subjects without the APOE4 allele . Am J Geriatr Psychiatry 2008 ; 16 : 781–5 . 21 . Verghese J , Lipton RB , Hall CB , Kuslansky G , Katz MJ . Low blood pressure and the risk of dementia in very old individuals . Neurology 2003 ; 61 : 1667–72 . 22 . Johnson DK , Wilkins CH , Morris JC . Accelerated weight loss may precede diagnosis in Alzheimer disease . Arch Neurol 2006 ; 63 : 1312–7 . 23 . Goldman WP , Morris JC . Evidence that age-associated memory impairment is not a normal variant of aging . Alzheimer Dis Assoc Disord 2001 ; 15 : 72–9 . 24 . Str and berg TE , Tilvis RS . C-reactive protein , cardiovascular risk factors , and mortality in a prospect i ve study in the elderly . Arterioscler Thromb Vasc Biol 2000 ; 20 : 1057– 60 . 25 . Schupf N , Tang MX , Albert SM et al. Decline in cognitive and functional skills increases mortality risk in nondemented elderly . Neurology 2005 ; 65 : 1218–26 . 26 . Williams GC . Pleiotropy , natural selection , and the evolution of senescence . Evolution 1957 ; 11 : 398–411 . 27 . Toupance B , Godelle B , Gouyon PH , Schachter F. A model for antagonistic pleiotropic gene action for mortality and advanced age . Am J Hum Genet 1998 ; 62 : 1525–34 . doi : 10.1093/ageing/afn278 Published electronically 15 January OBJECTIVE To determine how an ultra-brief structured tool that would require usually less than a minute for delirium assessment compares with a clinical assessment based on Diagnostic and Statistical Manual-IV ( DSM-IV ) in a geriatric postacute care ( PAC ) rehabilitation unit . DESIGN Prospect i ve observational cohort study . SETTING Postacute geriatric hospital ward of a Veteran 's Affairs hospital . PARTICIPANTS Consecutively admitted patients between 50 and 100 years old for inpatient postacute medical care . MEASUREMENTS Two teams , blinded to one another 's evaluations , performed daily delirium assessment s using either the Confusion Assessment Method for the intensive care unit ( CAM-ICU ) or clinical assessment based on DSM-IV . RESULTS There were 61 patients enrolled ( median 73 years old , range : 52 - 94 ) , who underwent 521 paired observations . Delirium was detected in 18 patients ( 29.5 % ) by one of the two screening methods over the course of the study , most of whom ( 14 patients , 23 % ) were delirious on the first day of enrollment . Delirium was identified by the CAM-ICU on 12.6 % of the observations and by the clinical assessment on 6 % of the observations ( κ = 0.25 , 95 % confidence interval [ CI ] : 0.09 , 0.40 ) . Examination of disagreement between the 2 evaluations revealed that patients with dementia ( κ = 0.11 , 95 % CI : -0.14 , 0.27 ) had 10.7 times higher odds ( 95 % CI : [ 3.1 , 36.8 ] , p value < .001 ) of having discordance than patients without dementia . CONCLUSIONS Different delirium assessment s may disagree depending on the study population . Dementia patients are especially challenging to evaluate for delirium Pfeiffer 's Short Portable Mental Status Question naire ( SPMSQ ) is a brief screening test for organic brain syndromes . The validity of the SPMSQ was evaluated in a r and om sample of 119 community residents and 282 consecutively admitted medical in patients . The SPMSQ proved to be a sensitive and specific screening test for moderate to severe dementia both in the community and hospital . Using the cut-off point ( number of errors accepted ) of three errors , the sensitivity of the test was 86.2 % and the specificity 99.0 % among medical in patients . The percentages in the community sample were 66.7 % and Output:	IMPLICATION S The Confusion Assessment Method was the most widely used instrument to identify delirium , however , specific training is required to ensure optimum performance . The Delirium Rating Scale and its revised version performed best in the psychogeriatric population but requires an operator with psychiatric training . The Nurses ' Delirium Screening Checklist appears best suited to the surgical and recovery room setting . The Single Question in Delirium shows promise in oncology patients . The Memorial Delirium Assessment Scale , while demonstrating good measures of validity in the surgical and palliative care setting , may be better used a measure of delirium severity .
MS22103	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Sleep disturbances and related daytime complaints are frequent in rheumatoid arthritis ( RA ) . The aim of the current study was therefore to evaluate the effect of a newer hypnotic on sleep structure and clinical parameters in RA . Forty out patients were r and omized to a two week treatment regimen with either 7.5 mg zopiclone or placebo at bedtime . Clinical examinations were performed before and after treatment and the degree of pain , fatigue , sleepiness , morning stiffness , and activities of daily living were assessed . Two sleep question naires were also completed weekly . Polysomnography was performed before the study and after 14 days of treatment . Recordings were evaluated using conventional sleep scoring as well as frequency analysis of the electroencephalography ( EEG ) . Patients in the zopiclone group had subjective improvement of sleep , but otherwise no differences in pain score or the other clinical parameters were found . Conventional sleep assessment s showed only minor changes during treatment , but frequency analysis demonstrated a shift from the lower towards the higher EEG frequencies in the active treatment group . Although the modulation of the EEG can represent a non-specific pharmacologic epiphenomenon , it might also reflect a disturbance of sleep microstructure . In conclusion , treatment with zopiclone may be of value for subjective sleep complaints in selected patients with RA , but it is doubtful whether hypnotics improve daytime symptoms in this patient group The efficacy of indomethacin 100 mg , diazepam 10 mg , and placebo in producing sleep , relieving night pain , and reducing the severity of morning stiffness , was compared in 18 patients in hospital with active classical or definite rheumatoid arthritis . There was no statistically significant difference in the preference of patients or sleep score among the three forms of treatment . Both indomethacin and diazepam were more effective than placebo in relieving night pain . Indomethacin decreased , but diazepam increased , morning stiffness in comparison to placebo . Neither active therapy produced significant side-effects A double-blind controlled trial was carried out in 18 in- patients with classical or definite rheumatoid arthritis to assess the effectiveness of night-time medication with 100 mg indomethacin plus 10 mg diazepam , 200 mg sulindac , and 200 mg sulindac plus 10 mg diazepam in improving sleep and reducing night pain and the duration of morning stiffness . Patients received each treatment regimen for 1 night . The results from the 17 patients completing the full trial protocol indicated that indomethacin plus diazepam was the most effective of the three regimens , although the differences did not reach conventional statistical significance . It is suggested that in further such studies with sulindac a larger dose and a longer duration of treatment should be used Seventeen of eighteen patients hospitalized for active rheumatoid arthritis completed a three-day r and omized , double-blind comparison of 100 mg indomethacin , 100 mg indomethacin with 10 mg diazepam and matching placebo as night medication . The results showed a consistent pattern in the four functions measured -- pain , morning stiffness , sleep score and patient preference . In each , indomethacin proved superior to placebo and the combined therapy better than indomethacin alone . From this it has been concluded that the combination of indomethacin and diazepam should now be considered the treatment of choice for maximum control of night pain and morning stiffness in rheumatoid arthritis OBJECTIVE To evaluate the effects of triazolam upon insomnia and daytime sleepiness in patients with rheumatoid arthritis ( RA ) . METHODS Triazolam or placebo was administered during two 7 night periods to 15 patients with RA in a double blind crossover study . Polysomnographic recordings were conducted on the last 2 nights of each condition , and multiple sleep latency tests and mood and arthritis assessment s were performed during the intervening day in each condition . RESULTS In the triazolam condition , total sleep time was increased , daytime sleepiness was reduced , and morning stiffness was improved compared to placebo . Objective measures of sleep fragmentation were unchanged . Clinical arthritis assessment s were similar during both conditions . CONCLUSION Short term hypnotic therapy improves sleep in patients with RA and appears to improve morning stiffness and daytime sleepiness Output:	Overall , the included trials failed to find evidence of a beneficial effect of muscle relaxants over placebo ( at 24 hours , 1 week , or 2 weeks ) or in addition to nonsteroidal antiiflammatory drugs ( at 24 hours ) on pain intensity , function , or quality of life . Based upon the currently available evidence in patients with IA , benzodiazepines ( diazepam and triazolam ) do not appear to be beneficial in improving pain over 24 hours or 1 week . The non-benzodiazepine agent zopiclone also did not significantly reduce pain over 2 weeks . However , even short-term muscle relaxant use ( 24 hours to 2 weeks ) is associated with significant adverse events , predominantly drowsiness and dizziness
MS22104	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The effect of hydroxychloroquine ( HCQ ) on dry eye has not been fully determined . This study aim ed to compare the 12-week efficacy of HCQ medication with that of a placebo in the management of dry eye in primary Sjögren 's syndrome ( pSS ) . A double-blind , r and omized control study was conducted in 39 pSS subjects from May 2011 through August 2013 . pSS was diagnosed based on the classification criteria of the American-European Consensus Group . Subjects received 300 mg of HCQ or placebo once daily for 12 weeks and were evaluated at baseline , 6 , and 12 weeks , with a re-visit at 16 weeks after drug discontinuance . The fluorescein staining score , Schirmer test score , tear film break-up time ( TBUT ) , and ocular surface disease index ( OSDI ) were measured , and tears and blood were collected for ESR , IL-6 , IL-17 , B-cell activating factor ( BAFF ) , and Th17 cell analysis . Color testing was performed and the fundus was examined to monitor HCQ complications . Twenty-six subjects completed the follow-up . The fluorescein staining score and Schirmer test score did not differ significantly . The OSDI improved with medication in the HCQ group but was not significantly different between the groups . TBUT , serum IL-6 , ESR , serum and tear BAFF , and the proportion of Th17 cells did not change in either group . HCQ at 300 mg daily for 12 weeks has no apparent clinical benefit for dry eye and systemic inflammation in pSS ( Clinical Trials.gov . NCT01601028 ) OBJECTIVE There is evidence to support a dominant role for B cells in the pathophysiology of primary Sjögren 's syndrome ( SS ) . Therefore , we evaluated the safety and efficacy of anti-CD20 monoclonal antibody . METHODS Sixteen patients who met the new American-European Consensus Group criteria for primary SS and scored > 50 on at least 2 of 4 visual analog scales ( VAS ; 100 mm ) evaluating global disease , pain , fatigue , and global dryness received infusions of low-dose rituximab ( 375 mg/m(2 ) ) at weeks 0 and 1 without steroid premedication . RESULTS Slow rituximab infusions ( 100 mg/hour ) were well tolerated , with only 1 patient experiencing serum sickness-like disease . There was a dramatic reduction in B cells of the blood and salivary gl and ( SG ) . At week 12 , VAS scores with respect to fatigue and dryness ( P < 0.05 ) , tender point count ( P < 0.035 ) , and quality of life as evaluated by the Short Form 36 question naire ( SF-36 ; P < 0.001 ) were significantly improved . At week 36 , significant improvements were noted in the 4 VAS scores ( P < 0.05 ) , tender joint count ( P = 0.017 ) , tender point count ( P = 0.027 ) , and SF-36 ( P < 0.03 ) . Pulmonary manifestations were ameliorated in 1 patient . Patients with improvements on at least 3 of the 4 VAS scores at any visit ( n = 11 ) had a shorter disease duration than the other patients ( n = 5 ; mean + /- SD duration 3.8 + /- 5.4 versus 30.1 + /- 29.5 years ; P = 0.02 ) . CONCLUSION Low-dose rituximab infusions were well tolerated without the benefit of steroids . Infusions induced a rapid depletion of B cells in the blood and SG and could improve primary SS . Controlled studies are needed The aim of this study was to evaluate the efficacy and safety of mycophenolate sodium ( MPS ) in patients with primary Sjögren syndrome ( pSS ) refractory to other immunosuppressive agents . Eleven patients with pSS were treated with MPS up to 1,440 mg daily for an observation period of 6 months in this single-center , open-label pilot trial . At baseline , after 3 months , and after 6 months , we examined the clinical status , including gl and ular function tests , as well as different laboratory parameters associated with pSS . In addition , subjective parameters were determined on the basis of different question naires . Treatment with MPS was well tolerated in 8 of 11 patients . Due to vertigo or gastrointestinal discomfort , two patients did not complete the trial . One patient developed pneumonia 2 weeks after treatment and was withdrawn . In the remaining patients , MPS treatment result ed in subjective improvement of ocular dryness on a visual analogue scale and a reduced dem and for artificial tear supplementations . However , no significant alterations of objective parameters for dryness of eyes and mouth were observed , although a substantial improvement of gl and ular functions occurred in two patients with short disease duration . In addition , treatment with MPS result ed in significant reduction of hypergammaglobulinemia and rheumatoid factors as well as an increase of complement levels and white blood cells . MPS promises to be an additional therapeutic option for patients with pSS , at least in those with shorter disease duration . Further investigations about the efficacy and safety of MPS in pSS have to be performed in larger numbers of patients Objectives Fatigue is a major cause of disability in primary Sjögren 's syndrome ( pSS ) . Fatigue has similarities with sickness behaviour in animals ; the latter mediated by pro-inflammatory cytokines , in particular interleukin (IL)-1 , acting on neuronal brain cells . We hypothesised that IL-1 inhibition might improve fatigue in pSS patients ; thus , we examined the effects and safety of an IL-1 receptor antagonist ( anakinra ) on fatigue . Methods Twenty-six pSS patients participated in a double-blind , placebo-controlled parallel group study . Patients were r and omised to receive either anakinra or a placebo for four weeks . Fatigue was evaluated by a fatigue visual analogue scale and the Fatigue Severity Scale . The primary outcome measure was a group-wise comparison of the fatigue scores at week 4 , adjusted for baseline values . Secondary outcome measures included evaluation of laboratory results and safety . The proportion of patients in each group who experienced a 50 % reduction in fatigue was regarded as a post-hoc outcome . All outcomes were measured at week 4 . Results There was no significant difference between the groups in fatigue scores at week 4 compared to baseline after treatment with anakinra . However , six out of 12 patients on anakinra versus one out of 13 patients on the placebo reported a 50 % reduction in fatigue VAS ( p = 0.03 ) . There were two serious adverse events in each group . Conclusions This r and omised , double-blind , placebo-controlled trial of IL-1 blockade did not find a significant reduction in fatigue in pSS in its primary endpoint . A 50 % reduction in fatigue was analysed post-hoc , and significantly more patients on the active drug than on placebo reached this endpoint . Although not supported by the primary endpoint , this may indicate that IL-1 inhibition influences fatigue in patients with pSS . Trial registration Clinical Trials.gov BACKGROUND Primary Sjögren syndrome ( pSS ) is an autoimmune disorder characterized by ocular and oral dryness or systemic manifestations . OBJECTIVE To evaluate efficacy and harms of rituximab in adults with recent-onset or systemic pSS . DESIGN R and omized , placebo-controlled , parallel-group trial conducted between March 2008 and January 2011 . Study personnel ( except pharmacists ) , investigators , and patients were blinded to treatment group . ( Clinical Trials.gov : NCT00740948 ) . SETTING 14 university hospitals in France . PATIENTS 120 patients with scores of 50 mm or greater on at least 2 of 4 visual analogue scales ( VASs ) ( global disease , pain , fatigue , and dryness ) and recent-onset ( < 10 years ) biologically active or systemic pSS . INTERVENTION R and omization ( 1:1 ratio ) to rituximab ( 1 g at weeks 0 and 2 ) or placebo . MEASUREMENTS Primary end point was improvement of at least 30 mm in 2 of 4 VASs by week 24 . RESULTS No significant difference between groups in the primary end point was found ( difference , 1.0 % [ 95 % CI , -16.7 % to 18.7 % ] ) . The proportion of patients with at least 30-mm decreases in at least two of the four VAS scores was higher in the rituximab group at week 6 ( 22.4 % vs. 9.1 % ; P = 0.036 ) . An improvement of at least 30 mm in VAS fatigue score was more common with rituximab at weeks 6 ( P < 0.001 ) and 16 ( P = 0.012 ) , and improvement in fatigue from baseline to week 24 was greater with rituximab . Adverse events were similar between groups except for a higher rate of infusion reactions with rituximab . LIMITATION Low disease activity at baseline and a primary outcome that may have been insensitive to detect clinical ly important changes . CONCLUSION Rituximab did not alleviate symptoms or disease activity in patients with pSS at week 24 , although it alleviated some symptoms at earlier time points OBJECTIVE To study the efficacy and safety of B cell depletion with rituximab , a chimeric murine/human anti-CD20 monoclonal antibody , in patients with primary Sjögren 's syndrome ( SS ) in a double-blind , r and omized , placebo-controlled trial . METHODS Patients with active primary SS , as determined by the revised American-European Consensus Group criteria , and a rate of stimulated whole saliva secretion of > or = 0.15 ml/minute were treated with either rituximab ( 1,000 mg ) or placebo infusions on days 1 and 15 . Patients were assigned r and omly to a treatment group in a ratio of 2:1 ( rituximab : placebo ) . Followup was conducted at 5 , 12 , 24 , 36 , and 48 weeks . The primary end point was the stimulated whole saliva flow rate , while secondary end points included functional , laboratory , and subjective variables . RESULTS Thirty patients with primary SS ( 29 female ) were r and omly allocated to a treatment group . The mean + /- SD age of the patients receiving rituximab was 43 + /- 11 years and the disease duration was 63 + /- 50 months , while patients in the placebo group were age 43 + /- 17 years and had a disease duration of 67 + /- 63 months . In the rituximab group , significant improvements , in terms of the mean change from baseline compared with that in the placebo group , were found for the primary end point of the stimulated whole saliva flow rate ( P = 0.038 versus placebo ) and also for various laboratory parameters ( B cell and rheumatoid factor [ RF ] levels ) , subjective parameters ( Multidimensional Fatigue Inventory [ MFI ] scores and visual analog scale [ VAS ] scores for sicca symptoms ) , and extragl and ular manifestations . Moreover , in comparison with baseline values , rituximab treatment significantly improved the stimulated whole saliva flow rate ( P = 0.004 ) and several other variables ( e.g. , B cell and RF levels , unstimulated whole saliva flow rate , lacrimal gl and function on the lissamine green test , MFI scores , Short Form 36 health survey scores , and VAS scores for sicca symptoms ) . One patient in the rituximab group developed mild serum sickness-like disease . CONCLUSION These results indicate that rituximab is an effective and safe treatment strategy for patients with primary SS OBJECTIVE To report the efficacy and safety of long-term treatment of SS with belimumab , targeting the B-cell-activating factor . METHODS Patients with primary SS were included in the BELISS open-label phase II study , a 1-year open-label trial , if they were positive for anti-SSA or anti-SSB antibodies and had systemic complications or persistent salivary gl and enlargement or early disease or biomarkers of B-cell activation . They received belimumab , 10 mg/kg i.v . , at weeks 0 , 2 and 4 and then every 4 weeks ; if response was observed at week 28 , or if the clinician and the patient agreed to continue the study in the absence of side effects , treatment was continued for 1 year . Efficacy and safety were analysed during the 1-year period of treatment . RESULTS Among the 30 patients recruited , 28 were evaluated at week 28 as already reported . Nineteen terminated the 52-week study , 15 of them being responders and 4 non-responders at week 28 . Thirteen of the 15 responders at week 28 also responded at week 52 ( 86.7 % ) . The improvement in the EULAR Sjögren 's Syndrome Disease Activity Index and EULAR Sjögren 's Syndrome Patient Reported Index scores observed at week 28 showed a trend to further improvement at week 52 , and the amelioration of peculiar EULAR Sjögren 's Syndrome Disease Activity Index domains ( gl and ular , lymphadenopathy , articular ) appeared of particular relevance . The decrease in biomarkers of B-cell activation observed at week 28 persisted unchanged until week 52 , with RF decreasing further . Salivary flow , Schirmer 's test and the focus score of salivary biopsy did not change . Safety of treatment was good . CONCLUSION Long-term treatment with belimumab may be beneficial in SS . R and omized , double-blind , Output:	Two Cochrane systematic literature review s ( SLRs ) have reported that topical treatments for dry mouth and dry eye are safe and effective . RCTs using infliximab , anakinra and baminercept found no placebo-differences for the primary outcomes . Conclusion The current evidence supporting the use of the main topical therapeutic options of primary SjS is solid , while limited data from RCTs are available to guide systemic therapies
MS22105	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Severe alcoholic hepatitis ( sAH ) is associated with a poor prognosis . There is no proven effective treatment for sAH , which is why early transplantation has been increasingly discussed . Hepatoblastoma‐derived C3A cells express anti‐inflammatory proteins and growth factors and were tested in an extracorporeal cellular therapy ( ELAD ) study to establish their effect on survival for subjects with sAH . Adults with sAH , bilirubin ≥8 mg/dL , Maddrey 's discriminant function ≥ 32 , and Model for End‐Stage Liver Disease ( MELD ) score ≤ 35 were r and omized to receive st and ard of care ( SOC ) only or 3‐5 days of continuous ELAD treatment plus SOC . After a minimum follow‐up of 91 days , overall survival ( OS ) was assessed by using a Kaplan‐Meier survival analysis . A total of 203 subjects were enrolled ( 96 ELAD and 107 SOC ) at 40 sites worldwide . Comparison of baseline characteristics showed no significant differences between groups and within subgroups . There was no significant difference in serious adverse events between the 2 groups . In an analysis of the intent‐to‐treat population , there was no difference in OS ( 51.0 % versus 49.5 % ) . The study failed its primary and secondary end point in a population with sAH and with a MELD ranging from 18 to 35 and no upper age limit . In the prespecified analysis of subjects with MELD < 28 ( n = 120 ) , ELAD was associated with a trend toward higher OS at 91 days ( 68.6 % versus 53.6 % ; P = .08 ) . Regression analysis identified high creatinine and international normalized ratio , but not bilirubin , as the MELD components predicting negative outcomes with ELAD . A new trial investigating a potential benefit of ELAD in younger subjects with sufficient renal function and less severe coagulopathy has been initiated . Liver Transplantation 24 380–393 2018 AASLD Abstract For patients with acute-on-chronic liver failure ( ACLF ) , artificial liver support system ( ALSS ) may help prolong lifespan and function as a bridge to liver transplantation ( LT ) , but data on its long-term benefit are lacking . We conducted this prospect i ve , controlled study to determine the efficacy of ALSS and the predictors of mortality in patients with hepatitis B virus (HBV)-associated ACLF.From January 2003 to December 2007 , a total of 234 patients with HBV-associated ACLF not eligible for LT were enrolled in our study . They were allocated to receive either plasma exchange centered ALSS plus st and ard medical therapy ( SMT ) ( ALSS group , n = 104 ) or SMT alone ( control group , n = 130 ) . All the patients were followed-up for at least 5 years , or until death . At 90 days , the survival rate of ALSS group was higher than that of the control group ( 62/104 [ 60 % ] vs 61/130 [ 47 % ] , respectively ; P < 0.05 ) . Median survival was 879 days in the ALSS group ( 43 % survival at 5 years ) and 649 days in the control group ( 31 % survival at 5 years , log-rank P < 0.05 ) . ALSS was found to be associated with favorable outcome of these patients by both univariate and multivariate analysis . Multivariate Cox regression analysis also revealed that lower serum sodium levels , higher grade s of encephalopathy , presence of cirrhosis , hepatorenal syndrome , and higher model for end-stage liver disease scores were independent predictors for both 90-day and 5-year mortality due to ACLF.Our findings suggest that ALSS is safe and may improve the short- and long-term prognosis of patients with HBV-associated ACLF The Molecular Adsorbent Recirculating System ( MARS ) has been proven to prolong survival in patients with hepatorenal syndrome . MARS is a modified dialysis that uses an albumin containing dialysate , which is recirculated and perfused online through charcoal and anion exchanger columns . It allows the selective removal of albumin bound substances . Despite advances in medical therapy and technology , the prognosis of patients with cardiogenic shock remains poor . Mortality rates are as high as 80 % , often because of persistent multiple organ failure . To determine whether patients with hypoxic liver failure after cardiogenic shock after cardiac surgery might benefit from MARS , we performed a prospect i ve , r and omized , controlled , single center study . The primary objective was to prove that MARS improves survival . This article is a report on the interim analysis of the first 27 patients included between August 2000 and December 2001 ; 14 patients were in the MARS group , and 13 patients were in the non-MARS group . All had bilirubin levels greater than 8 mg/ml . Both groups had a similar risk profile . The MARS group received MARS for 3 consecutive days — if bilirubin was still greater than 6 mg/dl afterward , MARS was continued . The non-MARS group received conventional therapy . We had seven survivors in the MARS group ( 50 % ) compared with four ( 32 % ; p = ns ) in the non-MARS group . We conclude that despite the limited number of patients included in this analysis , MARS can be recommended for patients with acute , hypoxic liver failure because it might prolong survival . Further studies in similar patient cohorts are needed to verify our results One hundred thirty-seven patients with fulminant hepatic failure were entered into two controlled trials of charcoal hemoperfusion carried out concurrently . In trial A , 75 patients with grade 3 encephalopathy were r and omized to receive 5 or 10 h of hemoperfusion daily . Overall survival rates for the two groups were similar ( 51.3 % vs. 50.0 % ) as was the frequency of major complications including cerebral edema and renal failure . In trial B , in which 62 patients with established grade 4 encephalopathy on admission were r and omized to a no-perfusion group or to have 10 h of hemoperfusion daily , overall survival rates for the two groups were again similar ( 39.3 % and 34.5 % , respectively ) . There was in both trials a significant relationship between survival and etiology quite independent of the use or duration of hemoperfusion . Thus , percentage survival for the acetaminophen-overdose cases was 52.9 % , for hepatitis A 66.7 % , for hepatitis B 38.9 % , for presumed non-A , non-B hepatitis 20 % , and for halothane or drug reaction 12.5 % . Within the etiologic subgroups survival was also influenced by the three major complications that developed , being inversely related to their frequency and combination , except in the non-A , non-B hepatitis and halothane or drug reaction subgroups , which had a high mortality throughout . In the latter cases particularly , orthotopic liver transplantation merits early consideration and in the group with better " intrinsic " survival ( acetaminophen , hepatitis A and B ) intensive management of complications ( rather than charcoal hemoperfusion ) would appear to be of major importance Output:	Because of this mistake , the difference between the artificial and control groups in Figure s6 1.8.1 was not statistically significant ( p = 0.09 ) , thereby failing to support the conclusion that the effect on mortality was more prominent with artificial devices than bio-artificial devices .
MS22106	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: CONTEXT Incidence of end-stage renal disease due to hypertension has increased in recent decades , but the optimal strategy for treatment of hypertension to prevent renal failure is unknown , especially among African Americans . OBJECTIVE To compare the effects of an angiotensin-converting enzyme ( ACE ) inhibitor ( ramipril ) , a dihydropyridine calcium channel blocker ( amlodipine ) , and a beta-blocker ( metoprolol ) on hypertensive renal disease progression . DESIGN , SETTING , AND PARTICIPANTS Interim analysis of a r and omized , double-blind , 3 x 2 factorial trial conducted in 1094 African Americans aged 18 to 70 years with hypertensive renal disease ( glomerular filtration rate [ GFR ] of 20 - 65 mL/min per 1.73 m(2 ) ) enrolled between February 1995 and September 1998 . This report compares the ramipril and amlodipine groups following discontinuation of the amlodipine intervention in September 2000 . INTERVENTIONS Participants were r and omly assigned to receive amlodipine , 5 to 10 mg/d ( n = 217 ) , ramipril , 2.5 to 10 mg/d ( n = 436 ) , or metoprolol , 50 to 200 mg/d ( n = 441 ) , with other agents added to achieve 1 of 2 blood pressure goals . MAIN OUTCOME MEASURES The primary outcome measure was the rate of change in GFR ; the main secondary outcome was a composite index of the clinical end points of reduction in GFR of more than 50 % or 25 mL/min per 1.73 m(2 ) , end-stage renal disease , or death . RESULTS Among participants with a urinary protein to creatinine ratio of > 0.22 ( corresponding approximately to proteinuria of more than 300 mg/d ) , the ramipril group had a 36 % ( 2.02 [ SE , 0.74 ] mL/min per 1.73 m(2)/y ) slower mean decline in GFR over 3 years ( P = .006 ) and a 48 % reduced risk of the clinical end points vs the amlodipine group ( 95 % confidence interval [ CI ] , 20%-66 % ) . In the entire cohort , there was no significant difference in mean GFR decline from baseline to 3 years between treatment groups ( P = .38 ) . However , compared with the amlodipine group , after adjustment for baseline covariates the ramipril group had a 38 % reduced risk of clinical end points ( 95 % CI , 13%-56 % ) , a 36 % slower mean decline in GFR after 3 months ( P = .002 ) , and less proteinuria ( P<.001 ) . CONCLUSION Ramipril , compared with amlodipine , retards renal disease progression in patients with hypertensive renal disease and proteinuria and may offer benefit to patients without proteinuria OBJECTIVE To evaluate the within-trial effect of losartan and conventional antihypertensive therapy ( CT ) compared with placebo and CT on the economic cost associated with end-stage renal disease ( ESRD ) . RESEARCH DESIGN AND METHODS The Reduction of End Points in Type 2 Diabetes With the Angiotensin II Antagonist Losartan ( RENAAL ) study was a multinational double-blind r and omized placebo-controlled clinical trial design ed to evaluate the renal protective effects of losartan on a background of CT ( excluding ACE inhibitors and angiotensin II receptor agonists [ AIIAs ] ) in patients with type 2 diabetes and nephropathy . The primary composite end point was doubling of serum creatinine , ESRD , or death . Data on the duration of ESRD were used to estimate the economic benefits of slowing the progression of nephropathy . The cost associated with ESRD was estimated by combining the days each patient experienced ESRD with the cost of ESRD over time . The cost of ESRD for individuals with diabetes was estimated using data from the U.S. Renal Data System . Total cost was estimated as the sum of the cost associated with ESRD and the cost of study therapy . RESULTS -We estimated that losartan and CT compared with placebo and CT reduced the number of days with ESRD by 33.6 per patient over 3.5 years ( P = 0.004 , 95 % CI 10.9 - 56.3 ) . This reduction in ESRD days result ed in a decrease in cost associated with ESRD of 5144 US dollars per patient ( P = 0.003 , 95 % CI 1701 to 8587 US dollars ) . After accounting for the cost of losartan , the reduction in ESRD days result ed in a net savings of 3522 US dollars per patient over 3.5 years ( P = 0.041 , 143 to 6900 US dollars ) . CONCLUSIONS Treatment with losartan in patients with type 2 diabetes and nephropathy not only reduced the incidence of ESRD , but also result ed in substantial cost savings Objective To investigate in a r and om comparison the capacity of an angiotensin converting enzyme inhibitor ( fosinopril ) , and that of a long-acting dihydropiridine ( nifedipine GITS ) to modify the decay in renal function in patients with primary renal disease , exhibiting a progressive increase in serum creatinine during the previous 2 years . Methods A r and omized , open-label , multicenter study with a minimum follow-up of 3 years . A total of 241 patients were included in the study . All of them were hypertensive and had a 25 % or at least 0.5 mg/dl increase in the value of serum creatinine during the 24 months prior to entering the study . Initial doses of fosinopril and nifedipine GITS were 10 and 30 mg respectively , and titration to 30 and 60 mg was performed if needed to obtain the expected blood pressure goal ( < 140/90 mmHg ) . Furosemide , atenolol , and doxazosin were added as second , third , and fourth drugs if necessary , for blood pressure control . The primary end-point of the study was the appearance of double the serum creatinine values and /or the need to enter a dialysis programme . Secondary end-points were cardiovascular events , death , changes in 24 h proteinuria , and the evolution of serum creatinine . Data reflect the analysis performed by intention to treat . Results Mean age of the group was 54 ± 14 , and 59 % were males . Primary glomerulonephritis ( 31 % ) , nephrosclerosis ( 26 % ) and polycystic kidney disease ( 19 % ) were the three most frequent diagnostic findings . After 3 years of follow-up , 21 % ( 27/127 ) of patients treated with fosinopril , and 36 % ( 40/112 ) of those receiving nifedipine GITS presented a primary end-point , ( OR 0.47 , 95 % confidence intervals 0.26–0.84 , P = 0.01 ) . Renal survival was significantly better when fosinopril constituted the first step therapy ( P = 0.002 ) . These results did not seem to be influenced by the type of primary renal disease . Proteinuria decreased at the end of the study by a mean of 57 % in the fosinopril group and increased by 7 % in the group receiving dihydropiridine . Blood pressure control did not differ among groups for diastolic values . During follow-up , however , the patients receiving ACEi showed systolic blood pressure values 4–6 mmHg lower . Conclusion In patients with chronic renal failure and hypertension due to primary renal disease , fosinopril significantly differed from nifedipine GITS by its capacity to slow the progressive decay in renal function . The drugs also differed by their capacity to lower blood pressure . The better control , in particular of systolic blood pressure , in the fosinopril arm could have contributed in a relevant manner to the attainment of a better outcome when the ACEi was employed Our study compared the effects of an angiotensin-converting enzyme inhibitor ( captopril ) versus a calcium antagonist ( nifedipine ) on proteinuria and renal function in patients with diabetic nephropathy . A r and omized follow-up study was design ed . Type 2 diabetic patients , with established diabetic nephropathy ( proteinuria greater than 0.5 g/24 h ) , were treated with nifedipine ( 10 patients , group A ) or captopril ( 10 patients , group B ) for 6 months . Arterial blood pressure , metabolic parameters , proteinuria and renal function were measured and compared . Mean percentage differences for glomerular filtration rate , renal plasma flow and filtration fraction between the two groups were calculated . No significant differences were observed in serum glucose , glycosylated hemoglobin ( hemoglobin A1c ) , Na+ , K+ or albumin in either group or between groups . Blood pressure decreased significantly with both treatments and mean blood pressure was significantly lower in group A compared with group B at 6 months ( Mann-Whitney U-test , P = 0.03 ) . Proteinuria was similar in both groups at r and omization , but after 3 and 6 months of treatment significant reductions were observed only in the group treated with captopril ( P less than 0.01 ) . A significant decrease in filtration fraction was observed in group B with an increase in group A ( Mann-Whitney U-test , P = 0.03 ) . Multiple regression analysis identified the therapeutic agent administered as an independent variable for decrease in proteinuria . It is concluded that antihypertensive treatment with captopril , but not with nifedipine , reduced proteinuria in patients with diabetic nephropathy , although a better mean blood pressure was obtained with nifedipine . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVES The goal of this study was to determine whether the level of kidney function is an independent risk factor for atherosclerotic cardiovascular disease ( ASCVD ) outcomes in the Atherosclerosis Risk in Communities ( ARIC ) study , a prospect i ve cohort study of subjects aged 45 to 64 years . BACKGROUND The level of kidney function is now recognized as a risk factor for ASCVD outcomes in patients at high risk for ASCVD , but it remains unknown whether the level of kidney function is a risk factor for ASCVD outcomes in the community . METHODS Cox proportional-hazards regression was used to evaluate the association of glomerular filtration rate ( GFR ) with ASCVD after adjustment for the major ASCVD risk factors in 15,350 subjects . We search ed for nonlinear relationships between GFR and ASCVD . RESULTS During a mean follow-up time of 6.2 years , 965 ( 6.3 % ) of subjects had ASCVD events . Subjects with GFR of 15 to 59 ml/min/1.73 m(2 ) ( n = 444 , hazard ratio 1.38 [ 1.02 , 1.87 ] ) and 60 to 89 ml/min/1.73 m(2 ) ( n = 7,665 , hazard ratio 1.16 [ 1.00 , 1.34 ] ) had an increased adjusted risk of ASCVD compared with subjects with GFR of 90 to 150 ml/min/1.73 m(2 ) . Each 10 ml/min/1.73 m(2 ) lower GFR was associated with an adjusted hazard ratio of 1.05 ( 1.02 , 1.09 ) , 1.07 ( 1.01 , 1.12 ) , and 1.06 ( 0.99 , 1.13 ) for ASCVD , de novo ASCVD , and recurrent ASCVD , respectively . A nonlinear model did not fit the data better than a linear model . CONCLUSIONS The level of GFR is an independent risk factor for ASCVD and de novo ASCVD in the ARIC study Angiotensin converting enzyme inhibitors and calcium antagonists are effective agents for controlling high blood pressure in diabetic patients . We selected 30 type II diabetic patients with proteinuria and evaluated the effect of these drugs on renal function and proteinuria . In a double-blind trial , patients received either 40 mg/day enalapril or 40 mg/day nifedipine during 12 months . They also received a hypoproteic diet with 0.8 g/kg wt/day of protein . In the enalapril group ( 10 men and eight women ) , mean arterial blood pressure was 112.0 + /- 12 mm Hg , creatinine clearance was 58.6 + /- 12.4 ml/min , and 24-hour proteinuria was 4.36 + /- 3.23 g/24 hr before treatment . After treatment , mean arterial blood pressure was 82.0 + /- 8.30 mm Hg ( p less than 0.001 ) , creatinine clearance was 66.6 + /- 13.8 ml/min ( NS ) , and 24-hour proteinuria was 0.56 + /- 0.78 g/24 hr ( p less than 0.001 ) . In the nifedipine group ( six men and six women ) , mean arterial blood pressure was 114.0 + /- 8.0 mm Hg , creatinine clearance was 67.8 + /- 19.6 ml/min Output:	RESULTS After adjusting for sample size , study length , and baseline value , there were no statistically significant differences in the ability of either class of calcium antagonist to decrease blood pressure . Consistently greater reductions in proteinuria were associated with the use of NDCAs compared with DCAs , despite no significant differences in blood pressure reduction or presence of diabetes . This analysis supports ( 1 ) similar efficacy between subclasses of calcium antagonists to lower blood pressure , and ( 2 ) greater reductions in proteinuria by NDCAs compared to DCAs in the presence or absence of diabetes . Based on these findings , NDCAs , alone or in combination with an angiotensin-converting enzyme ( ACE ) inhibitor or an angiotensin receptor blocker ( ARB ) , are suggested as preferred agents to lower blood pressure in hypertensive patients with nephropathy associated with proteinuria
MS22107	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: One hundred and twenty early lactating Holstein dairy cows were assigned to investigate the effect of dietary chromium ( Cr ) supplementation ( 0 or 6 mg Cr/head/day from organic preparation ) on the productive and reproductive performance as well as on some blood serum parameters under heat stress ( 35 - 40 degrees C ) . Cows received treatment from 3 weeks pre-partum through 12 weeks post-partum . Chromium supplemented diet had lower body weight loss and improved dry matter intake with consequent reduction in the energy balance deficits during the first period after calving when compared with the control group . Chromium supplementation increased ( p < 0.05 ) milk yield by 6.7 % , 12.3 % and 16.5 % at 4 , 8 and 12 weeks post-partum , respectively , whereas milk composition and milk to feed ratio were unaffected ( p > 0.05 ) when compared with the control . Moreover , dietary Cr supplementation had no effect ( p > 0.05 ) on blood serum glucose , calcium and phosphorus concentrations . A reduction ( p < 0.05 ) of non-esterified fatty acids at 1 week pre-partum , 2 and 4 weeks post-partum was also observed . Serum insulin concentration increased whereas cortisol concentration decreased , when compared with the control group , throughout the whole experimental period . Also Cr supplementation showed a trend towards improving reproductive performance as indicated by increased percentage of pregnant cows in the first 28 days of breeding . It could be concluded that dietary Cr supplementation at level of 6 mg/head/day may offer a potential protective management practice to lessen the effect of heat stress in dairy cattle OBJECTIVE To evaluate the effects of length of exposure to prepartum transition diets on milk yield , fat and protein production . DESIGN Prospect i ve cohort study . The number of days that the cows were fed the prepartum transition diets was the exposure of interest . PROCEDURES Holstein and Holstein x Jersey cows ( n = 1008 ) were enrolled . Diets given in the far-off dry period ( from end of lactation until approximately 3 weeks before expected parturition ) consisted of ad libitum access to perennial ryegrass pastures . Prepartum transition diets included perennial ryegrass pasture , ryegrass silage , cereal hay , grain , grain by-product , protein meals , BioChlor , sodium monensin , virginiamycin or tylosin , MgSO(4 ) , trace elements and vitamins . On a dry matter basis , these contained 16.0 % crude protein , 4.2 % rumen undegradable protein , and 9.9 mJ metabolisable energy/kg . Diets provided an estimated metabolisable protein balance of 286 g/day and dietary cation anion difference of -150 meq/kg dry matter . Statistical models controlled for effects of herd , calving day , breed , age and gestation period . RESULTS Increasing length of exposure to the prepartum transition diets significantly increased the 4.0 % fat- and 3.2 % protein-corrected milk yield and milk-protein yield as a linear and quadratic effect . The optimal duration of exposure to the prepartum transition diets was 25 days for fat- and protein-corrected milk production and 22 days for milk protein production . Milk-fat percentage decreased significantly and linearly with increasing exposure to the prepartum transition diets ; however , milk-fat yield or milk-protein percentage did not vary significantly with duration of exposure to the diets . CONCLUSIONS Increasing exposure to prepartum transition diets increased milk and milk-protein yields and decreased the milk fat-percentage , but not the milk-protein percentage or milk-fat yield Milk protein concentration in dairy cows has been positively associated with a range of measures of reproductive performance . It was possible that these associations were due to confounding by milk volume . A retrospective single cohort study was conducted using data collected from 74 dairy herds with seasonal or split calving patterns . Associations between milk protein concentration and reproductive performance in Holstein dairy cows were assessed using r and om effects logistic regression . The key finding from this study was that the associations between milk protein concentration in early lactation and reproductive performance were not due to confounding by milk yield . Associations between milk protein concentration and reproductive performance were weaker at higher early lactation milk yields , but positive associations were evident at all milk volumes assessed . The second major finding was that increases in milk yield were associated with improved proportions of cows pregnant by wk 6 and 21 at low to moderate milk protein concentrations but with decreases in these reproductive measures at high milk protein concentrations . Thus , no simple relationship is present between milk yield and reproductive performance ; effects of milk yield depend on milk protein concentration . These results indicate that mechanisms causing the associations between milk protein concentration and reproductive performance may be linked to milk yield but these mechanisms operate over a wide range of milk yields ( < 2,000 to ≥5,000 kg in the first 120d of lactation ) . Further research is required to identify the causes of these associations Twenty preparturient dairy cows were in a 2-yr switchover design to test effects of dietary ions on incidence of milk fever . In yr 1 , cows were blocked and assigned r and omly 45 days prepartum to one of two diets ; one diet contained an excess of anions , and the second diet contained an excess of cations . In yr 2 , cows were changed to the opposite diet . Both diets were equivalent for crude protein ( 11 % ) , calcium ( .65 % ) , phosphorus ( .25 % ) , and energy on a dry basis but differed for quantities of chlorine , sulfur , and sodium . Both diets were chopped alfalfa hay , corn silage , high moisture corn , and vitamin-mineral mix . Diets were available ad libitum as complete rations . There were no differences in dry matter intake of the diets . Cows consuming the anionic diet had no milk fever , but cows consuming the canionic diet had 47.4 % incidence . Sample s of blood plasma showed that cows consuming the anionic diet maintained calcium and phosphorus through parturition , whereas cows consuming the cationic diet decreased in these minerals around calving . Hydroxyproline was higher for cows consuming the anionic diet during the peripartal period compared to cows consuming the cationic diet . Milk produced in the lactation subsequent to prepartum treatment was 6.8 % less for cows offered the cationic diet . When milk production of paretic and nonparetic cows offered the cationic diet was compared , milk was reduced 14 % with milk fever Forty-six multiparous Holstein cows were assigned at 5 d postpartum to a completely r and omized design employing a 2 x 3 factorial arrangement of treatments . Factors were 0 and 5 % added prilled long-chain fatty acids ( DM basis ) and three forage to concentrate ratios ( 45:55 , 64:36 , 84:16 ) . Diets consisted of immature alfalfa silage and a concentrate of shelled corn and soybean meal with or without fat replacing a portion of the corn . Mean plasma concentration of cholesterol was higher for cows fed 5 % vs. 0 % fat and increased over the first 100 d in milk for all animals regardless of treatment . There were no differences in reproductive performance due to either of the main effects . Mean plasma progesterone was higher due to fat treatment in the mid to late luteal phase of the second postpartum cycle as well as the metestrous to early luteal phase and mid to late luteal phase of the third cycle . Even though progesterone concentrations were higher in cows fed 5 % fat during the luteal phase after breeding , the conception rates at this service were not different from those fed 0 % fat . The biological significance of increased plasma progesterone concentration was not identified with any postpartum reproductive trait measured in this trial Conjugated linoleic acid ( CLA ) reduces mammary milk fat synthesis in a dose-dependent manner . Our objective was to determine the effects of lipid-encapsulated CLA ( LE-CLA ) supplementation on milk production , reproductive performance and metabolic responses in lactating dairy cows fed a grass silage-based diet . Seventy-two Holstein-Friesian cows ( 32 primiparous and 40 multiparous ) were used in a completely r and omized block design . Cows received either 80 g of LE-CLA daily or 60 g of calcium salts of palm fatty acids daily ( control ) from parturition until 60 days in milk . LE-CLA contained a 50:50 mix of cis-9,trans-11 CLA and trans-10,cis-12 CLA , result ing in a daily intake of 6 g of each isomer . Milk production and dry matter intake were recorded daily , and blood sample s were collected 3-times a week . Blood sample s were analysed for circulating concentrations of glucose , non-esterified fatty acids ( NEFA ) , β-hydroxybutyrate ( BHBA ) , insulin and insulin-like growth factor-I ( IGF-I ) . Progesterone was measured in blood sample s collected after the first post-partum insemination . Ovarian ultrasound examinations commenced at 8 - 10 d post partum and were carried out 3-times a week until first ovulation . LE-CLA treatment result ed in decreased milk fat concentration , with consequent improvements in energy balance and body condition score ( BCS ) . The peak concentration of NEFA in blood was reduced by LE-CLA , but circulating concentrations of insulin , glucose , IGF-I , BHBA and progesterone were not affected . There was no effect of LE-CLA supplementation on the post-partum interval to first ovulation . Services per conception tended to be reduced . The reduction in milk energy output and improvement in energy status and BCS in LE-CLA-supplemented cows provides a strong rationale for further studies with greater cow numbers to test effects on reproductive performance Clinical mastitis and reproductive records from two southern California dairy herds were used in a cross-sectional study to determine the risk of an altered interestrus interval following clinical mastitis . An altered interestrus interval was defined as cycles occurring at either less than 18 day or more than 24-day intervals . The data were stratified by herd to assess herd differences and by lactation number to assess confounding by cow parity . The predominant pathogen isolated from mastitis cases in Herd 1 was Staphylococcus aureus , whereas the predominant pathogens in Herd 2 were gram-negative isolates . Cows in Herd 1 which had coliforms cultured from mastitic milk were excluded in the analysis for comparison with Herd 2 . In Herd 1 , cows with clinical mastitis were less likely to have an altered interestrus interval ( Relative Risk [RR]=0.9 ; 95 % Confidence Interval [CI]=0.6,1.6 ) than herdmates without clinical mastitis . However , cows in Herd 2 were almost two times more likely to have an altered interestrus interval following an episode of clinical mastitis compared to herdmates without clinical mastitis ( RR=1.6 ; 95 % CI=1.3,2.0 ) . Because herd management practice s differ and could cause differences in mastitis and reproductive outcomes at the dairies , this preliminary field evidence should be followed by prospect i ve studies of luteal function after clinical coliform mastitis The effects of grain , fructose , and histidine on ruminal pH and fermentation products were studied in dairy cattle during an induced subacute acidosis protocol . Thirty Holstein heifers were r and omly allocated to 5 treatment groups : ( 1 ) control ( no grain ) ; ( 2 ) grain [ fed at a crushed triticale dry matter intake ( DMI ) of 1.2 % of body weight ( BW ) ] ; ( 3 ) grain ( 0.8 % of BW DMI)+fructose ( 0.4 % of BW DMI ) ; ( 4 ) grain ( 1.2 % of BW DMI)+histidine ( 6 g/head ) ; and ( 5 ) grain ( 0.8 % of BW DMI)+fructose ( 0.4 % of BW DMI)+histidine ( 6 g/head ) in a partial factorial arrangement . Heifers were fed 1 kg of grain daily with ad libitum access to ryegrass silage and alfalfa hay for 10 d. Feed was withheld for 14 h before challenge day , on which heifers were fed 200 g of alfalfa hay and then the treatment diets immediately thereafter . Rumen sample s were collected 5 min after diet ingestion , 60 min later , and at 3 subsequent 50-min intervals . Grain decreased ruminal pH and increased ammonia , total volatile fatty acid ( VFA ) , acetate , butyrate , propionate , and valerate concentrations compared with controls . The addition of grain had no effect on ruminal D- and L-lactate concentrations . Fructose markedly decreased ruminal pH and markedly increased D- and L-lactate concentrations . Fructose increased total VFA and butyrate and decreased valerate concentrations . Although histidine did not have a marked effect on ruminal fermentation , increased concentrations of histamine were observed following feeding . This study demonstrates that the substitution of some grain for fructose can lower ruminal pH and increase VFA and lactate concentrations , warranting further investigation into the role of sugars on the risk of acidosis in dairy cattle The aim of this study was to investigate the relationship between measures of body condition score collected from calving until wk 26 of lactation and reproductive measures ( calving interval , days to first heat , days to first service , and conception at first service ) . Since 19 Output:	There was no multivariable model developed to assess variables associated with calving to pregnancy interval but , univariably , increased metabolizable energy balance was associated with a shorter calving to pregnancy interval whereas increased milk production was associated with longer time to pregnancy . Increased intake of some AA , particularly threonine and lysine , were associated with a longer calving to pregnancy interval . It is clear nutritional management around calving can influence reproductive success . The importance of dietary fats and increased energy and protein balances in early lactation for improved fertility outcomes is supported and suggests that starch and sugars may have different effects on the proportion of cows that are pregnant to AI .
MS22108	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objective : To determine changes in depression and anxiety after resective surgery . Methods : Data from subjects enrolled in a prospect i ve multicenter study of resective epilepsy surgery were review ed with the Beck Psychiatric Symptoms Scales ( Beck Depression Inventory [ BDI ] and Beck Anxiety Inventory [ BAI ] ) and Composite International Diagnostic Interview ( CIDI ) up to a 24-month period . χ2 analyses were used to correlate proportions . Results : A total of 358 presurgical BDI and 360 BAI results were review ed . Moderate and severe levels of depression were reported in 22.1 % of patients , and similar levels of anxiety were reported by 24.7 % . Postoperative rates of depression and anxiety declined at the 3- , 12- , and 24-month follow-up periods . At the 24-month follow-up , moderate to severe levels of depression symptoms were reported in 17.6 and 14.7 % of the patients who continued to have postoperative seizures . Moderate to severe depression and anxiety were found in 8.2 % of those who were seizure-free . There was no relationship , prior to surgery , between the presence or absence of depression and anxiety and the laterality or location of the seizure onset . There were no significant relationships between depression or anxiety at 24-month follow-up and the laterality or location of the surgery . Conclusions : Depression and anxiety in patients with refractory epilepsy significantly improve after epilepsy surgery , especially in those who are seizure-free . Neither the lateralization nor the localization of the seizure focus or surgery was associated with the risk of affective symptoms at baseline or after surgery PURPOSE Psychological interventions in the treatment of epilepsy have been developed and evaluated for many years but the amount of research has hardly made an impact on how epilepsy is treated . The purpose of this study was to develop and evaluate a psychological treatment program consisting of acceptance and commitment therapy ( ACT ) together with some behavioral seizure control technology shown to be successful in earlier research . METHODS The method consisted of a r and omized controlled trial group design with repeated measures ( n=27 ) . All participants had an EEG verified epilepsy diagnosis with drug refractory seizures . Participants were r and omized into one of two conditions , ACT or supportive therapy ( ST ) . Therapeutic effects were measured by examining changes in quality of life ( SWLS and WHOQOL ) and seizure index ( frequency x duration ) . Both treatment conditions consisted of only nine hours of professional therapy distributed in two individual and two group sessions during a four-week period . RESULTS The results showed significant effects over all of the dependent variables for the ACT group as compared to the ST group at six- and twelve-month follow-ups . CONCLUSIONS The results from this study suggest that a short-term psychotherapy program combined with anticonvulsant drugs may help to prevent the long-term disability that occurs from drug refractory seizures OBJECTIVES The goals of this study were to observe behavioral changes in patients receiving levetiracetam ( LEV ) , a newer antiepileptic drug ( AED ) , and to answer the question of whether LEV exerts a specific effect on impulse control and aggression . METHODS We asked 288 consecutive patients with epilepsy on LEV ( 90 % polytherapy , mean dose=2689 mg ) and 135 relatives whether LEV caused a positive or negative behavioral change . Forty-three patients on other AEDs served as a control group . Ratings were related to patient characteristics , efficacy , dose , drug load , bidirectional ratings of change in behavioral domains , and question naires on personality ( Fragebogens zur Persönlichkeit bei zerebralen Erkrankungen ) and impulsivity ( Barratt Impulsiveness Scale-11 ) . RESULTS LEV was rated as very effective by 40 % of the patients . In contrast to only 9 % of the controls , a considerable number of patients reported a behavioral change while taking LEV ( 12 % very negative , 25 % negative , 16 % positive , 6 % very positive ) . Negative ratings were due to loss of self-control , restlessness , sleep problems , and , most importantly , aggression . Positive ratings were due to increased energy , vigilance , and activation . Increases in psychomotor speed , concentration , and remote memory indicated subjectively experienced positive effects on cognition . The proxy reports indicated reliable self-reports . Reported change was not related to type of epilepsy , co-therapy , dose , drug load , or psychiatric history . Negative effects were , however , associated with poorer seizure control , mental retardation , indicators of an organic psychosyndrome , and nonplanning impulsiveness . CONCLUSION The results indicate that LEV exerts a dose-independent stimulating effect that can be positive or negative . Aggression is a prominent feature . Lack of efficacy , mental retardation , and presumably also pre-intake disposition ( organic psychosyndrome , impulsivity ) may be helpful in predicting whether additional activation under LEV will be positive or negative A few previous studies have revealed impairments in remote memory in patients with temporal lobe epilepsy , but many questions about the importance of lesion side , type of material , seizure history and deficits in other aspects of cognitive functions remain unanswered . In this study , patients who had undergone unilateral ( 15 right and 15 left ) temporal lobectomy ( TL ) for the relief of epilepsy and 15 control subjects completed a range of public and autobiographical memory tests . Deficits in recall and recognition of details related to past famous world events were observed for both left and right TL groups . In addition , the left TL group showed impaired retrieval of famous names and TL patients as a group generated significantly fewer names of people from their own past . Current seizure- and medication-status influenced performance on a few measures , but duration of epilepsy and age of onset had no significant impact . Underlying cognitive deficits ( especially naming ability ) contributed to , but could not completely explain difficulties remembering the past . In particular , deficits in the ability to retrieve highly specific information learned in the past , such as names of famous people or details about famous events , remained evident in analyses that controlled for the impact of related cognitive skills Considerable interest has been focused on the psychiatric complications of medically refractory temporal lobe epilepsy ( TLE ) before and after epilepsy surgery . The aim of the present study was to evaluate the psychiatric status , quality of life , and level of disability in medically refractory mesial temporal lobe epilepsy ( MTLE ) patients , a homogenous subgroup of patients with TLE , before and after anterior temporal lobectomy ( ATL ) . The study population consisted of 22 patients with medically refractory MTLE who were c and i date s for ATL . Patients were examined before surgery as well as in the third and sixth months of the postoperative period . Psychiatric diagnosis was determined by using SCID-I. To rate the severity of psychiatric disorders , BPRS , HDRS , and HARS were employed on each visit . WHO-DAS-II and WHOQOL-BREF were used to determine the level of disability and quality of life . Preoperatively , six patients had a psychiatric diagnosis . Three months after surgery , six of the patients had psychiatric diagnoses . Five of these six patients had not been previously diagnosed . There was no significant difference between preoperative and postoperative follow-up evaluations in terms of HDRS , HARS , and BPRS ratings . With respect to the total scores and domains of WHO-DAS-II , the change in pre- and postoperative evaluations was statistically significant only for the social life attendance domain . There was no significant difference in the mean scores on the WHOQOL-BREF domains or on the first question about general evaluation of quality of life . For the second question on the level of satisfaction with health , the difference between the three ratings was statistically significant . Preoperative and postoperative rates of psychiatric disorders in our sample were low . While social phobia was frequently seen preoperatively , the postoperative period was spearheaded by major depressive disorder . The decrease in disability in attendance to social life and improvement in the quality of health were in concordance with the literature , indicating the positive results of surgical treatment of epilepsy on quality of life . This study suggests that surgical intervention might be one of the causes of postoperative psychiatric disorders in patients with MTLE Objective – To explore effectiveness , tolerability and changes in quality of life in patients with epilepsy converting to topiramate ( TPM ) from carbamazepine ( CBZ ) or oxcarbazepine ( OXC ) due to insufficient effectiveness and /or tolerability Quality of life is impaired in patients with epilepsy and can be improved by effective therapy . R and omised clinical trials have shown that lamotrigine treatment is associated with improved quality of life . However , little information is available on quality of life or treatment effects in patients with epilepsy in the general population . The objective of this study was to estimate the impact of lamotrigine on quality of life in a naturalistic treatment setting . The study included adult patients with epilepsy in whom lamotrigine therapy was initiated . Each subject completed the Quality of Life in Epilepsy Inventory (QOLIE)-31 quality of life question naire at inclusion and at a follow-up visit in the next 4 months . Demographic information and medical history were provided by the investigator . These were evaluated as potential determinants of change in quality of life using logistic regression . Three hundred and forty-one patients were evaluated , 192 starting lamotrigine in combination with another drug , 90 as a first-line monotherapy , 45 as a switch from another drug and 14 as a reduction to monotherapy from a previous combination . Baseline scores on the QOLIE-31 ranged from 53.8 in the combination group to 69.5 in the first-line group . 34.6 % of patients were considered to be responders , with no significant differences between treatment regimen . Most improvement was seen for the energy-fatigue and medication effects subscales and , for the first-line group , seizure worry . Seizure type was the only determinant of improvement of quality of life identified . In conclusion , lamotrigine treatment is associated with improved quality of life , regardless of treatment regimen The aim of this prospect i ve , multicenter , open-label study was to investigate the efficacy of levetiracetam ( LEV ) and determine its effects on cognitive and neuropsychological function . Sixty-nine patients were evaluated for effects of LEV on seizure control , cognitive ( Mini-Mental State Examination [ MMSE ] ) and neuropsychological ( Symptom Checklist-90 Revised [ SCL-90-R ] ) functions , and quality of life ( Quality of Life in Epilepsy--10 [ QOLIE-10 ] ) assessment s at 3 and 12 months of follow-up . Thirty-nine percent of patients achieved seizure freedom , and 68 % had a > or = 50 % seizure frequency reduction after 1 year of LEV ( 1235.5+/-392.7 mg/day ) . There were also significant improvements in mean MMSE score and in the recall and language items of MMSE . There were modest improvements in interpersonal sensitivity and paranoid ideation scales of the SCL-90-R , and improvements in cognition and medication effect items of the QOLIE-10 . The results demonstrate that LEV not only effectively reduces seizure frequency , but also possibly contributes to improvements in neuropsychological functions such as recall , language , interpersonal sensitivity , and paranoid ideation PURPOSE To assess anger/hostility during treatment with lamotrigine adjunctive therapy versus levetiracetam adjunctive therapy in patients with partial seizures . METHODS This r and omized , double-blind , parallel-group study in adults with partial seizures included an 8-week escalation phase , during which adjunctive lamotrigine ( n = 132 ) or adjunctive levetiracetam ( n = 136 ) was titrated to a target dose , and a 12-week , double-blind maintenance phase , during which dosages of study medication and concomitant antiepileptic drugs were maintained . The primary endpoint was change from baseline to the end of the maintenance phase ( week 20 ) in the Anger-Hostility subscale score of the Profile of Mood States ( POMS ) . RESULTS Improvement with lamotrigine relative to levetiracetam was observed for mean + /- SD ( st and ard deviation ) change from baseline to the end of the maintenance phase ( week 20 ) on the Anger-Hostility subscale ( lamotrigine -2.0 + /- 8.2 , levetiracetam -0.3 + /- 8.4 ; p = 0.024 ) ( the primary endpoint ) ; the Anger-Hostility subscale on weeks 5 , 6 , 7 , 8 , 9 , 11 , 12 , 14 , 16 , 18 , and 19 ; and the Total Mood Disturbance score on weeks 6 , 7 , 8 , 9 , 11 , 12 , 17 , 19 , and 20 . Improvement ( p < 0.05 ) with lamotrigine relative to levetiracetam was also observed on the POMS subscales Depression-Dejection , Vigor-Activity , Fatigue-Inertia , and Confusion-Bewilderment . No difference in seizure frequency was observed between groups . The most common adverse events with both medications were headache and dizziness . DISCUSSION Adjunctive lamotrigine significantly improved Anger-Hostility subscale scores relative to adjunctive levetiracetam in patients with partial seizures at the end of 20 weeks . This difference was consistently observed throughout the treatment period . Similar improvement with lamotrigine versus levetiracetam was observed for other mood symptoms AIM The purpose of this prospect i Output:	The most frequent PSDs found in people with epilepsy were depressive symptoms , memory functions , quality of life , anxiety , stigma , locus of control , cognitive functions in general , and emotional functions in general . It can be stated that patients ' life areas are affected by cognitive , emotional , and psychological problems .
MS22109	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To show clinical benefit in the main outcome measures by the use of a st and ardized protocol for identification , characterization , and treatment of alcohol withdrawal syndrome ( AWS ) in postoperative patients with head and neck cancer . DESIGN Prospect i ve cohort study with a retrospective cohort control . SETTING Tertiary care university . PATIENTS A total of 26 consecutive postoperative patients with AWS were selected from among 652 patients with head and neck cancer to be enrolled in the protocol from March 2003 through March 2005 . Controls consisted of 14 of 981 consecutive patients with AWS from March 2000 through December 2002 . INTERVENTION Application of a st and ardized care protocol . MAIN OUTCOME MEASURES Sensitivity and specificity of preoperative screening for AWS risk , predictability of outcomes , length of stay , transfers to the intensive care unit ( ICU ) , AWS symptoms , postoperative morbidity and mortality , doses of pharmacotherapy required , and charges . RESULTS Protocol patients demonstrated significantly fewer AWS-related ICU transfers and less delirium and violence than pre protocol patients . Mortality , wound complications , hospital charges , and doses of benzodiazepines , clonidine , and haloperidol were not significantly different between these 2 groups . Preoperative medical history correlated poorly with AWS outcomes . Screening was 87.5 % sensitive and 99.7 % specific . Late enrollees to the protocol ( false-negative screening results ) showed many significantly worse outcomes than immediate enrollees . CONCLUSION Use of the st and ardized AWS symptom-triggered protocol decreased delirium , violence , and AWS-related ICU transfers without significantly increasing hospital charges Abstract Objective : To evaluate the influence of preoperative abstinence on postoperative outcome in alcohol misusers with no symptoms who were drinking the equivalent of at least 60 g ethanol/day . Design : R and omised controlled trial . Setting : Copenhagen , Denmark . Subjects : 42 alcoholic patients without liver disease admitted for elective colorectal surgery . Interventions : Withdrawal from alcohol consumption for 1month before operation ( disulfiram controlled ) compared with continuous drinking . Main outcome measures : Postoperative complications requiring treatment within the first month after surgery . Perioperative immunosuppression measured by delayed type hypersensitivity ; myocardial ischaemia and arrhythmias measured by Holter tape recording ; episodes of hypoxaemia measured by pulse oximetry . Response to stress during the operation were assessed by heart rate , blood pressure , serum concentration of cortisol , and plasma concentrations of glucose , interleukin 6 , and catecholamines . Results : The intervention group developed significantly fewer postoperative complications than the continuous drinkers ( 31 % v 74 % , P=0.02 ) . Delayed type hypersensitivity responses were better in the intervention group before ( 37 mm2 v 12 mm2 , P=0.04 ) , but not after surgery ( 3 mm2 v 3 mm2 ) . Development of postoperative myocardial ischaemia ( 23 % v 85 % ) and arrhythmias ( 33 % v 86 % ) on the second postoperative day as well as nightly hypoxaemic episodes ( 4 v 18 on the second postoperative night ) occurred significantly less often in the intervention group . Surgical stress responses were lower in the intervention group ( P≤0.05 ) . Conclusions : One month of preoperative abstinence reduces postoperative morbidity in alcohol abusers . The mechanism is probably reduced pre clinical organ dysfunction and reduction of the exaggerated response to surgical stress In a prospect i ve study of 7735 middle-aged 7 British men , 504 of whom died in a follow-up period of 7.5 years , there was a U-shaped relationship between alcohol intake and total mortality and an inverse relationship with cardiovascular mortality , even after adjustment for age , cigarette smoking , and social class . These mortality patterns were seen in all smoking categories ( with ex-smoking non-drinkers having the highest mortality ) and were observed in manual but not in non-manual workers . The alcohol-mortality relationships ( total and cardiovascular ) were present only in men with cardiovascular or cardiovascular-related doctor-diagnosed illnesses at initial examination . The data suggest that the observed alcohol-mortality relationships are produced by pre-existing disease and by the movement of men with such disease into non-drinking or occasional-drinking categories . The concept of a " protective " effect of drinking on mortality , ignoring the dynamic relationship between ill-health and drinking behaviour , is likely to be ill founded AIM To assess the effectiveness of a tailored pre-operative intervention for excessive alcohol consumption in reducing post-operative complications and alcohol consumption thereafter . METHODS Patients scheduled for elective surgery requiring at least overnight hospitalisation were screened for alcohol misuse . Consenting , eligible participants with > or = 7 days to surgery at the time of screening were offered an intervention and those with < 7 days to surgery were provided usual care . RESULTS Over a period of 2 years and 10 months , 3139 patients were screened to recruit 136 participants . Baseline analysis revealed a mean age of 53 ( + /-15.8 ) years and a mean consumption of 71 g/day ( + /-48.1 ) . The intervention group ( n = 45 ) did not differ significantly from controls ( n = 91 ) in age , consumption , and number of current smokers , but there were significantly more women in the control group . There was no difference between the groups in major or minor complications experienced , or length of stay after controlling for age , gender , and baseline consumption . At 6-month follow-up there was a significant reduction in drinking for the entire study population . CONCLUSION The study did not demonstrate any beneficial effect of the pre-operative intervention on post-operative complications . The relatively short time to surgery , intervention by a non-member of the surgical team , challenges to recruitment and reduced consumption in the control group may have limited the ability of the study to detect a significant effect of the intervention Postoperative morbidity after hysterectomy was prospect ively studied in 229 consecutive patients in our departments . The incidence of alcohol abuse ( greater than 60 gm of alcohol daily ) and social drinking ( between 25 and 60 gm of alcohol daily ) was 6.5 % for each . When compared with the social drinkers and the control group , the alcohol abuse group had significantly more complications ( 80 % vs 27 % and 80 % vs 13 % , respectively ) PURPOSE Morbidity after radical cystectomy is common and associated with increased health care re source use . Accurate characterization of complications after cystectomy , associated patient specific risk factors , and perioperative processes of care are essential to directing changes in perioperative management that will reduce morbidity and improve the quality of patient care . MATERIAL S AND METHODS The National Surgical Quality Improvement Program ( NSQIP ) is a prospect i ve quality management initiative of 123 Veterans Affairs Medical Centers nationwide . The NSQIP collects clinical information , intraoperative data and outcomes on a wide variety of surgical procedures from multiple surgical disciplines . Since 1991 , 2,538 radical cystectomy procedures have been captured by the NSQIP . Modeling using logistic regression was performed to identify patient specific risk factors and perioperative process measures associated with postoperative morbidity . RESULTS Of the 2,538 subjects at least 1 postoperative complication developed in 774 ( 30.5 % ) . The most frequent complication was ileus ( 10 % ) . Several factors were associated with the development of a complication , including age , dependent functional status , preoperative dyspnea , preoperative acute renal failure , chronic steroid use , preoperative alcohol consumption , American Society of Anesthesiology score , use of general anesthetic , operative time , intraoperative blood requirement and surgeon level of training . CONCLUSIONS Morbidity remains high after cystectomy with 30.5 % of subjects experiencing at least 1 complication . Measurable patient specific risk factors and perioperative processes associated with postoperative morbidity following cystectomy are now delineated which allows for improved risk stratification , patient counseling , and the development of novel processes that may incrementally reduce risk and improve outcomes There are many papers comparing two antibiotic protocol s for the profilaxis of head and neck infections after laryngeal surgery . We present one prospect i ve and r and omised study in 60 patients comparing the efficacy of two protocol s. The comparison was between ceftriaxone versus the association of clindamicyn and gentamicyn . In our data base we included the risk factors for infection , the surgical approach , the duration of surgery and the patient characteristics . We observed an incidence of 28 % of infection , with a 23.3 % in the clindamicyn + gentamicyn group and a 33.3 % in the ceftriaxone group . The differences between the two groups were not statistically significant . In this study we observed a small difference between the amount of alcohol comsuption , the effectiveness of the surgical drainage , the surgical approach and the presence of wound infection . The difference was not statistical significant due to the small group of patients . The profilaxis was adequate for the total laryngectomy and cordectomy group , with a higher incidence of wound infection in patients treated with a supraglottic laryngectomy Study Design . This is a multivariate analysis of a prospect ively collected data base . Objective . To determine preoperative , intraoperative , and patient characteristics that contribute to an increased risk of postoperative wound infection in patients undergoing spinal surgery . Summary of Background Data . Current literature sites a postoperative infection rate of approximately 4 % ; however , few have completed multivariate analysis to determine factors which contribute to risk of infection . Methods . Our study identified patients who underwent a spinal decompression and fusion between 1997 and 2006 from the Veterans Affairs ’ National Surgical Quality Improvement Program data base . Multivariate logistic regression analysis was used to determine the effect of various preoperative variables on postoperative infection . Results . Data on 24,774 patients were analyzed . Wound infection was present in 752 ( 3.04 % ) patients , 287 ( 1.16 % ) deep , and 468 ( 1.89 % ) superficial . Postoperative infection was associated with longer hospital stay ( 7.12 vs. 4.20 days ) , higher 30-day mortality ( 1.06 % vs. 0.5 % ) , higher complication rates ( 1.24 % vs. 0.05 % ) , and higher return to the operating room rates ( 37 % vs. 2.45 % ) . Multivariate logistic regression identified insulin dependent diabetes ( odds ratios [ OR ] = 1.50 ) , current smoking ( OR = 1.19 ) ASA class of 3 ( OR = 1.45 ) or 4 to 5 ( OR = 1.66 ) , weight loss ( OR = 2.14 ) , dependent functional status ( 1.36 ) preoperative HCT < 36 ( 1.37 ) , disseminated cancer ( 1.83 ) , fusion ( OR = 1.24 ) and an operative duration of 3 to 6 hours ( OR = 1.33 ) or > 6 hours ( OR = 1.40 ) as statistically significant predictors of postoperative infection . Conclusion . Using multivariate analysis of a large prospect ively collected data from the National Surgical Quality Improvement Program data base , we identified the most important risk factors for increased postoperative spinal wound infection . We have demonstrated the high mortality , morbidity , and hospitalization costs associated with postoperative spinal wound infections . The information provided should help alert clinicians to presence of these risks factors and the likelihood of higher postoperative infections and morbidity in spinal surgery patients RATIONALE Postoperative pneumonia is three to four times more frequent in patients with alcohol use disorders followed by prolonged intensive care unit ( ICU ) stay . Long-term alcohol use leads to an altered perioperative hypothalamus-pituitary-adrenal ( HPA ) axis and immunity . OBJECTIVES The aim of this study was to evaluate HPA intervention with low-dose ethanol , morphine , or ketoconazole on the neuroendocrine-immune axis and development of postoperative pneumonia in long-term alcoholic patients . METHODS In this r and omized , double-blind controlled study , 122 consecutive patients undergoing elective surgery for aerodigestive tract cancer were included . Long-term alcohol use was defined as consuming at least 60 g of ethanol daily and fulfilling the Diagnostic and Statistical Manual of Mental Disorders IV criteria for either alcohol abuse or dependence . Nonalcoholic patients were included but only as a descriptive control . Perioperative intervention with low-dose ethanol ( 0.5 g/kg body weight per day ) , morphine ( 15 mug/kg body weight per hour ) , ketoconazole ( 200 mg four times daily ) , and placebo was started on the morning before surgery and continued for 3 d after surgery . Blood sample s to analyze the neuroendocrine-immune axis were obtained on the morning before intervention and on Days 1 , 3 , and 7 after surgery . MEASUREMENTS AND MAIN RESULTS In long-term alcoholic patients , all interventions decreased postoperative hypercortisolism and prevented impairment of the cytotoxic T-lymphocyte type 1:type 2 ratio . All interventions decreased the pneumonia rate from 39 % to a median of 5.7 % and shortened int Output:	When drinkers and moderate drinkers were compared , a significantly higher incidence of surgical site infection and anastomotic leakage was found in unadjusted studies . In the meta- analysis of studies adjusting for smoking and age , alcohol drinking did not significantly affect surgical site infection and anastomotic leakage . The RCTs did not show any effect of perioperative alcohol abstinence or pharmacological withdrawal treatment on outcome . Conclusions Alcohol drinking is not an independent risk factor for surgical site infection and anastomotic leakage . Interventions which aim to make patients quit alcohol or treat withdrawal symptoms do not seem to affect the surgical outcomes of interest
MS22110	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Clinical officers perform much of major emergency surgery in Malawi , in the absence of medical officers . The aim of this study was to vali date the advantages and disadvantages of delegation of major obstetric surgery to non-doctors . Methods During a three month period , data from 2131 consecutive obstetric surgeries in 38 district hospitals in Malawi were collected prospect ively . The interventions included caesarean sections alone and those that were combined with other interventions such as subtotal and total hysterectomy repair of uterine rupture and tubal ligation . All these surgeries were conducted either by clinical officers or by medical officers . Results During the study period , clinical officers performed 90 % of all straight caesarean sections , 70 % of those combined with subtotal hysterectomy , 60 % of those combined with total hysterectomy and 89 % of those combined with repair of uterine rupture . A comparable profile of patients was operated on by clinical officers and medical officers , respectively . Postoperative outcomes were almost identical in the two groups in terms of maternal general condition – both immediately and 24 hours postoperatively – and regarding occurrence of pyrexia , wound infection , wound dehiscence , need for re-operation , neonatal outcome or maternal death . Conclusion Clinical officers perform the bulk of emergency obstetric operations at district hospitals in Malawi . The postoperative outcomes of their procedures are comparable to those of medical officers . Clinical officers constitute a crucial component of the health care team in Malawi for saving maternal and neonatal lives given the scarcity of physicians To assess whether trained nursing personnel could provide IUD services as safely and effectively as physicians in Brazil , an experimental study was conducted at the main clinic of the Center for Research on Integrated Maternal and Child Care in Rio de Janeiro . From November 1984 through April 1986 , a total of 1,711 women who requested IUD insertion at the clinic were r and omly assigned to have a Copper-T 200 IUD inserted by one of the clinic 's 11 physicians or 13 nurses . All of the physicians and nursing staff members who provided these services had taken the Center 's st and ard clinical family planning training course . Of 860 insertions attempted by the physicians and nurses , 1.3 % and 3.3 % , respectively , were unsuccessful . Statistically , this difference was very significant ( P < 0.01 ) . Also , mainly because the cervix was small and undilated , nulliparous women had a relatively high insertion failure rate of 8.0 % , as compared to 1.5 % for primiparas and 1.0 % for multiparas . The overall rate of complications at insertion was 1.8 % , these complications including diaphoresis , vomiting , syncope , cervical laceration , and one case of perforation of the uterus ; no significant difference was found between the complication rates for insertions performed by physicians as compared to nurses . However , 9.0 % of the study subjects reported severe pain during IUD insertion , with significantly higher percentages reporting pain if the IUD was inserted by a physician , or if the subject was nulliparous , had preinsertion symptoms , or had a history of pelvic inflammatory disease ( PID ) or sexually transmitted disease ( STD ) . It was also found that the nurses had a dramatically high insertion failure rate ( 11.6 % ) with nulliparous subjects , while the physicians ' failure rate with such subjects was a significantly lower 3.4 % . No significant difference was found in the groups served by nurses and physicians with regard to postinsertion complaints or termination of use within 12 months of insertion . These findings suggest that future training , besides preparing nursing personnel in IUD insertion , should emphasize preparation in taking the client 's medical history and diagnosing existing medical symptoms that could be associated with IUD insertion complications . In addition , if a nulliparous woman requests an insertion , it should be performed by a physician or more experienced nursing staff member with close medical supervision . Because of high rates of reported pain at insertion , such women , as well as those with medical symptoms associated IUD insertion complications and those with a history of PID or STD , should be considered c and i date s for extra care and counseling . ( ABSTRACT TRUNCATED AT 400 WORDS A shortage of doctors limits the provision of post-partum sterilisation services in rural areas of Thail and . To overcome this problem nurse-midwives with theatre experience were trained to perform post-partum tubal ligation by a mini-laparotomy incision under local anaesthesia . The performance of the nurse-midwives was compared with that of doctors in a controlled , r and omised clinical trial . Some operative difficulty was encountered by the nurses in 4.9 % of cases and by the doctors in 2.0 % of cases . This difference is not statistically significant and arose largely because the nurse-midwife cases were more obese . Nurse-midwives required a significantly longer operating-time ( 18.5 min ) than doctors ( 11.9 min ) . However , postoperative morbidity was similar in the two groups ( 7.0 % and 6.0 % , respectively ) . These results suggest that trained nurse-midwives with theatre experience can safely provide post-partum sterilisation services . A further field trial is underway BACKGROUND Tubal sterilization is an increasingly common method of contraception in the United States . Although pregnancy after sterilization is uncommon , it can occur and may be ectopic . We used data from the U.S. Collaborative Review of Sterilization to estimate the risk of ectopic pregnancy in women who had undergone the common types of tubal sterilization . METHODS A total of 10,685 women undergoing tubal sterilization were followed in a multicenter , prospect i ve cohort study . We intended to follow all the women for 5 years by means of annual telephone interviews ; for women enrolled early in the study , we attempted an additional follow-up telephone interview 8 to 14 years after sterilization . To assess the risk of ectopic pregnancy in these women , we used cumulative life-table probabilities and proportional-hazards analysis . RESULTS There were 47 ectopic pregnancies in the 10,685 women ; the 10-year cumulative probability of ectopic pregnancy for all methods of tubal sterilization combined was 7.3 per 1000 procedures . The cumulative probability varied substantially according to the method of sterilization and the woman 's age at the time of sterilization . Women sterilized by bipolar tubal coagulation before the age of 30 years had a probability of ectopic pregnancy that was 27 times as high as that among women of similar age who underwent postpartum partial salpingectomy ( 31.9 vs. 1.2 ectopic pregnancies per 1000 procedures ) . The annual rate of ectopic pregnancy for all methods combined in the 4th through 10th years after sterilization was no lower than that in the first 3 years . CONCLUSIONS A history of tubal sterilization does not rule out the possibility of ectopic pregnancy , even many years after the procedure Several studies have shown that nurses , nurse midwives , and paramedical personnel can provide satisfactory IUD services , but restrictions are still placed upon their provision of these services . A r and omized trial of auxiliary nurse midwife and physician IUD services was conducted among 495 interval acceptors in Turkey and 510 postpartum acceptors in the Philippines between 1976 and 1979 to further evaluate this question . Discontinuations due to expulsion , removal , and pregnancy were comparable for physician and nurse midwife clients . Among Filipino women who experienced an early expulsion , nurse midwives reinserted a device in significantly more cases ( 54.5 % ) than physicians ( 31.3 % ) . The diagnosis of contraindications or complications were similar in the 2 groups . Turkish women frequently refused to have pelvic examinations by male physicians , and in the Philippines , nurse midwives provided better follow up than physicians . It is concluded that auxiliary nurse midwives can provide clinical services comparable to those provided by doctors , and may give better continuity of care because they are more accessible and acceptable to clients OBJECTIVE To compare the safety and quality of contraceptive injections by community-based health workers with those of clinic-based nurses in a rural African setting . METHODS A nonr and omized community trial tested provision of injectable Depo Provera ( DMPA ) by community reproductive health workers and compared it with routine DPMA provision at health units in Nakasongola District , Ug and a. The primary outcome measures were safety , acceptability and continuation rates . FINDINGS A total of 945 new DMPA users were recruited by community workers , clinic-based nurses and midwives . Research ers successfully followed 777 ( 82 % follow-up ) : 449 community worker clients and 328 clinic-based clients . Ninety-five percent of community-worker clients were " satisfied " or " highly satisfied " with services , and 85 % reported receiving information on side-effects . There were no serious injection site problems in either group . Similarly , there was no significant difference between continuation to second injection ( 88 % among clients of community-based workers , 85 % among clinic-going clients ) , nor were there significant differences in other measures of safety , acceptability and quality . CONCLUSION Community-based distribution ( CBD ) of injectable contraceptives is now routine in some countries in Asia and Latin America , but is practically unknown in Africa , where arguably the need for this practice is greatest . This research reinforces experience from other regions suggesting that well-trained community health workers can safely provide contraceptive injections Insertion of IUDs by trained non-physicians is increasing . This secondary analysis of TCu380A IUD acceptors collected at clinics in Nigeria , Turkey and Mexico involved 367 women ; 193 insertions were performed by physicians and 174 by non-physicians . Women having their IUD inserted by a non-physician were more likely to experience a pain-free insertion , but also likelier to have the IUD removed for bleeding and pain or to experience an expulsion than women who had their IUD inserted by a physician . Early discontinuation rates were similar between the two groups . Overall continuation rates were statistically higher for IUDs inserted by physicians only at the Mexico site . Trained non-physicians can probably safely insert the TCu380A IUD . Appropriate competency-based training is required to limit the number of expulsions and removals for bleeding and pain by non-physicians OBJECTIVE To assess safety associated with tubal ligation performed by trained clinical officers ( COs ) in rural Ug and a. METHODS Between March and June 2012 , 518 women in 4 regions of Ug and a were recruited into a prospect i ve cohort study and followed at days 3 , 7 , and 45 after undergoing tubal ligation performed by a trained CO . Intraoperative and postoperative adverse events ( minor , moderate , or major ) , and acceptability were assessed . RESULTS Mean age was 36 years ( range , 20 - 49 years ) and mean number of living children was 6.7 ( range , 0 - 15 ) . The overall rate of major adverse events was 1.5 % : 0.4 % intraoperatively ; 1.9 % at day 3 ; and 0.2 % at day 7 . The majority of women who underwent tubal ligation reported a good/very good experience at the facility ( range , 94%-99 % ) and would recommend the health services to a friend ( range , 93%-98 % ) . CONCLUSION In the present study , task sharing of tubal ligation to trained COs in private facilities was safe . Women reported high levels of satisfaction with the procedure . Training COs could be an effective strategy for exp and ing family-planning services to rural Ug and Output:	CONCLUSIONS Well- design ed clinical trials , of adequate sample size , are urgently needed to establish the safety , efficacy and acceptability of task sharing tubal sterilization to midlevel providers
MS22111	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: In a double-blind , placebo-controlled study we investigated the effects of dietary fish oil supplementation on arterial wall characteristics in 20 patients with non-insulin-dependent diabetes mellitus . Estimates reflecting compliance values in the large arteries and more peripheral vasculature , as measured by pulse-contour analysis , improved significantly after 6 weeks of fish oil therapy compared with values recorded at baseline and after 6 weeks ' administration of olive oil . The large-artery compliance estimate increased from 1.50 ( confidence interval [ CI ] , 1.31 to 1.69 ) mL/mm Hg at baseline to 1.68 ( CI , 1.52 to 1.84 ) mL/mm Hg after fish oil administration ( P < .01 ) . The oscillatory compliance value increased from 0.015 ( CI , 0.011 to 0.019 ) mL/mm Hg at baseline to 0.022 ( CI , 0.016 to 0.028 ) mL/mm Hg after fish oil ingestion ( P < .05 ) . No changes occurred in arterial blood pressure , cardiac output , stroke volume , or systemic vascular resistance with either intervention . The improved compliance estimates with fish oil ingestion occurred without altering fasting blood glucose and cholesterol concentrations . These results support the hypothesis that fish oils alter vascular reactivity and favorably influence arterial wall characteristics in patients with non-insulin-dependent diabetes mellitus . These direct vascular effects , expressed at the level of the vessel wall , may contribute to the cardioprotective actions of fish oil in humans Summary This study was conducted to examine the effect of ω3 fatty acid supplementation on plasma lipid , cholesterol and lipoprotein fatty acid content of non-insulin-dependent diabetic individuals consuming a higher ( 0.65 , n = 10 ) or lower ( 0.44 , n = 18 ) ratio of dietary polyunsaturated to saturated fatty acid ( P/S ) . The participants were initially given an olive oil supplement ( placebo ) equivalent to 35 mg of 18:1 · kg body weight–1 · day–1 for 3 months . This was followed by two ω3 supplement periods in a r and omized crossover . In these 3-month periods , participants were given a linseed oil supplement equivalent to 35 mg of 18:3ω3 · kg body weight–1 · day–1 or a fish oil supplement equivalent to 35 mg of 20:5ω3 + 22:6ω3 · kg body weight–1 · day–1 . At the end of each supplement period , a blood sample was drawn from each participant for lipid , lipoprotein , insulin , glucagon and C-peptide analyses . At the end of each 3-month period a 7-day dietary record was completed to calculate dietary fat intake and P/S ratio . Results indicate that fish oil significantly reduced plasma triacylglycerol level ( p < 0.05 ) and increased 20:5ω3 and 22:6ω3 content of all lipoprotein lipid classes . Linolenic acid supplementation had no effect on plasma triacylglycerol level , but it increased 18:3ω3 content of lipoprotein cholesterol ester fractions ( p < 0.05 ) . A slight increase in 20:5ω3 , but not 22:6ω3 , content was noted in lipoprotein lipid classes as a result of 18:3ω3 supplementation . LDL and HDL cholesterol , insulin , glucagon and C-peptide levels were not affected by either ω3 supplement . It is concluded that a modest intake of ω3 fatty acids , such as could be obtained from consuming fish regularly , will reduce plasma triglyceride level without affecting LDL or HDL cholesterol levels . [ Diabetologia ( 1997 ) 40 : 45–52 BACKGROUND There is conflicting evidence on the benefits of foods rich in vitamin E ( alpha-tocopherol ) , n-3 polyunsaturated fatty acids ( PUFA ) , and their pharmacological substitutes . We investigated the effects of these substances as supplements in patients who had myocardial infa rct ion . METHODS From October , 1993 , to September , 1995 , 11,324 patients surviving recent ( < or = 3 months ) myocardial infa rct ion were r and omly assigned supplements of n-3 PUFA ( 1 g daily , n=2836 ) , vitamin E ( 300 mg daily , n=2830 ) , both ( n=2830 ) , or none ( control , n=2828 ) for 3.5 years . The primary combined efficacy endpoint was death , non-fatal myocardial infa rct ion , and stroke . Intention-to-treat analyses were done according to a factorial design ( two-way ) and by treatment group ( four-way ) . FINDINGS Treatment with n-3 PUFA , but not vitamin E , significantly lowered the risk of the primary endpoint ( relative-risk decrease 10 % [ 95 % CI 1 - 18 ] by two-way analysis , 15 % [ 2 - 26 ] by four-way analysis ) . Benefit was attributable to a decrease in the risk of death ( 14 % [ 3 - 24 ] two-way , 20 % [ 6 - 33 ] four-way ) and cardiovascular death ( 17 % [ 3 - 29 ] two-way , 30 % [ 13 - 44 ] four-way ) . The effect of the combined treatment was similar to that for n-3 PUFA for the primary endpoint ( 14 % [ 1 - 26 ] ) and for fatal events ( 20 % [ 5 - 33 ] ) . INTERPRETATION Dietary supplementation with n-3 PUFA led to a clinical ly important and statistically significant benefit . Vitamin E had no benefit . Its effects on fatal cardiovascular events require further exploration The short-term effect of high fiber intake on fish-oil treatment in 15 free-living , non-insulin-dependent diabetic patients was evaluated by using a controlled , sequential study design . During an 8-wk fish-oil-treatment period when patients received 20 g fish oil/d , the usual daily fiber intake was increased with a 15-g pectin supplement at midpoint . Fish oil alone lowered triacylglycerol and very-low-density-lipoprotein-cholesterol concentrations by 41 % and 36 % , respectively ( both P < 0.01 by the end of the treatment period ) with unchanged mean total , low-density- , and high-density-lipoprotein-cholesterol concentrations . When the fiber intake was increased , however , total and low-density-lipoprotein-cholesterol concentrations decreased significantly ( P < 0.001 and < 0.05 , respectively ) with fish-oil treatment . The cholesterol ester fraction of plasma lipids was reduced by 34 % when compared with fish oil alone ( P < 0.05 ) . The plasma triacylglycerol fraction decreased further by 44 % ( P < 0.001 ) . Other beneficial effects observed included a 30 % decline in the fatty acid fraction ( P < 0.002 ) by end of the treatment period . Diabetic control was maintained during the 12-wk study . In conclusion , a high fiber intake may be beneficial in fish oil-treated diabetic patients Fish-oil supplementation decreases serum triacylglycerols but may worsen hyperglycemia in patients with non-insulin-dependent diabetes mellitus . The reason for the possible deterioration of glycemia is unclear . We examined whether inhibition of triacylglycerol synthesis by n-3 fatty acids changes lipolysis , glycerol gluconeogenesis , or fatty acid oxidation . Nine obese patients with non-insulin-dependent diabetes mellitus participated in a r and omized double-blind crossover study in which 6 wk of n-3 fatty acid supplementation ( 12 g fish oil ) was compared with 6 wk of corn plus olive oil . Serum triacylglycerols decreased by 30 % during n-3 fatty acid supplementation . Glycerol gluconeogenesis ( [U-14C]glycerol ) increased by 32 % . However , overall glucose production ( [3 - 3H]glucose ) , glycemic control , and fatty acid oxidation remained unchanged . Thus , 6 wk of n-3 fatty acid supplementation lowers triacylglycerols in patients with non-insulin-dependent diabetes mellitus without worsening glycemic control . However , n-3 fatty acid supplementation increases glycerol gluconeogenesis , which could contribute to deterioration of glycemic control during long-term treatment with high doses of fish-oil supplements A multicenter , r and omized , double-blind , place-bo-controlled study evaluated the possible worsening of glycemic control after a moderate daily intake of n-3 fatty acid ethyl esters in patients with hypertriglyceridemia with and without glucose intolerance or diabetes . A total of 935 patients of both sexes in 63 Italian clinical centers were selected ; 55 % had either impaired glucose tolerance or non-insulin-dependent diabetes mellitus ( NIDDM ) . They received for 2 mo either 1 g n-3 ethyl esters three times a day or a corresponding placebo , followed by 4 mo of either 1 g n-3 ethyl esters twice a day or placebo . In addition to the complete lipid and lipoprotein evaluation , patients with impaired glucose tolerance also underwent an oral-glucose-tolerance test ; in patients with NIDDM , serum insulin and glycated hemoglobin ( Hb A1c ) concentrations were determined . Plasma triacylglycerol concentrations decreased significantly , up to 21.53 % at 6 mo compared with baseline ( decreased 15 % compared with placebo ) , with a tendency toward a progressive reduction with time . There was no evidence for a different response in patients with either NIDDM or impaired glucose tolerance . Among NIDDM patients , the triacylglycerol reduction was greater in those with high-density-lipoprotein cholesterol < or = 0.91 mmol/L. There was no alteration in the major glycemic indexes : fasting glucose , Hb A1c , insulinemia , and oral glucose tolerance in patients with impaired glucose tolerance or NIDDM after treatment with n-3 ethyl esters . Treatment with a moderate daily dose of n-3 ethyl esters over a prolonged period of time significantly reduced triacylglycerol concentrations without any worsening of glucose tolerance in patients with hypertriglyceridemia with and without impaired glycemic regulation Diabetic control as judged by five criteria did not deteriorate after 6 months of fish oil compared to 6 months of olive oil supplementation in 16 patients with NIDDM who were eating a low fat , high complex carbohydrate diet . Plasma total and VLDL triglyceride and cholesterol decreased significantly after fish oil supplementation ; plasma total and HDL cholesterol concentrations did not change . The LDL cholesterol level was significantly increased with fish oil supplementation , suggesting that patients with NIDDM who are given a fish oil supplement to decrease the plasma total and VLDL triglyceride levels may also need further dietary and /or pharmaceutical therapy to maintain an LDL cholesterol level compatible with a low risk of coronary disease . The study emphasizes the safe use of fish oil over a 6-month period in diabetic patients The effect of fish oil and corn oil supplementation on plasma lipids and lipoproteins and on low density lipoprotein ( LDL ) oxidation was examined in 20 treated hypertensive subjects . The r and omized double-blind crossover study consisted of two 6-week interventions with 4 g/day of a highly purified fish oil or corn oil . Fish oil significantly ( -24 % , P < 0.01 ) reduced plasma triglyceride , and increased LDL-cholesterol ( + 6 % , P < 0.01 compared to corn oil ) . LDL particles were larger ( P < 0.01 ) after fish oil compared to baseline and LDL size was inversely correlated with plasma triglyceride ( P < 0.001 ) both before and after fish oil supplementation , and positively correlated with high density lipoprotein cholesterol ( P < 0.01 ) . Fish oil reduced lag time before onset of copper-induced LDL oxidation ( -25 % , P < 0.001 ) and significantly increased production of thiobarbituric acid-reactive substances ( TBARS ) during oxidation , compared with corn oil . Corn oil had no significant effect on lag time and oxidation rate . Fish oil increased macrophage uptake of copper-oxidized LDL and of macrophage-modified LDL . Corn oil was without effect . Additionally , macrophages that were supplemented with fish oil fatty acids in vitro displayed a significantly ( P < 0.001 ) higher capacity to oxidize LDL than either control cells or cells supplemented with corn oil fatty acids . We conclude that from the st and point of atherosclerosis , fish oil fatty acids adversely raise the susceptibility of LDL to copper-indu Output:	No statistically significant effect was observed for fasting glucose , HbA1c , total or HDL cholesterol . The triglyceride lowering effect and the elevation in LDL cholesterol were most marked in those trials that recruited people with hypertriglyceridemia and used higher doses of fish oil . REVIEW ER 'S CONCLUSIONS Fish oil supplementation in type 2 diabetes lowers triglycerides , may raise LDL cholesterol ( especially in hypertriglyceridemic patients on higher doses of fish oil ) and has no statistically significant effect on glycemic control .
MS22112	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: PURPOSE To assess the short-term effect of laser peripheral iridotomy ( LPI ) on anterior segment anatomy in angle-closure suspects using ultrasound biomicroscopy ( UBM ) . DESIGN Prospect i ve intervention study . PARTICIPANTS Persons identified as angle-closure suspects aged 50 - 79 years from a population -based survey in Guangzhou , China . INTERVENTION Laser peripheral iridotomy was performed on 1 r and omly selected eye . Ultrasound biomicroscopy examination was carried out before and 2 weeks after the intervention . MAIN OUTCOME MEASURES Proportion of eyes with iridotrabecular contact ( ITC ) , as well as changes in UBM parameters including angle opening distance ( AOD ) , iris thickness ( IT ) , iris curvature , iris ciliary process distance , trabecular-ciliary process distance ( TCPD ) , and scleral spur to iris insertion distance ( SS-IR ) . RESULTS A total of 72 of 101 eligible subjects participated in the study . The proportion of people with UBM-identified ITC in > or = 1 quadrant dropped from 95 % ( 68/72 ) before to 59 % ( 42/72 ) after LPI . After LPI , the mean AOD at 250 microns increased from 0.064 mm ( st and ard deviation [ SD ] , 0.052 ) to 0.085 ( 0.052 ) mm ( P<0.001 ) ; angle recess area increased from 0.040 ( 0.030 ) to 0.070 ( 0.036 ) mm2 ( P<0.0001 ) ; TCPD increased from 0.537 to 0.561 mm ( P = 0.001 ) ; IT at 750 microns increased from 0.440 to 0.459 mm ( P = 0.094 ) , and IT at 1000 microns increased from 0.471 to 0.488 mm ( P = 0.0001 ) . Eyes whose angles remained closed after LPI ( pigmented trabecular meshwork not visible in > or =3 quadrants ) tended to have shallower AOD both at 250 ( 0.071 vs. 0.049 mm ; P = 0.09 ) and 500 microns ( 0.108 vs. 0.052 mm ; P = 0.001 ) , a thicker iris ( IT at 750 microns , 0.447 vs. 0.415 mm ; P = 0.041 ) , a more anterior positioned ciliary body ( TCPD , 0.514 vs. 0.562 mm ; P = 0.03 ) , and a statistically nonsignificant more anterior iris insertion ( SS-IR : 0.085 vs. 0.125 mm ; P = 0.061 ) , before LPI . CONCLUSIONS Laser peripheral iridotomy results in a significant increase in the angle width in Chinese people with narrow angles . However , some iridotrabecular contact was found in 59 % of eyes with a patent iridotomy . This was associated with smaller anterior chamber angle dimensions and a thicker iris , both of which may play a causative role in maintaining angle closure after LPI AIM To compare visual acuity and intraocular pressure outcomes 3 years after treatment of acute angle closure glaucoma ( AACG ) by operative peripheral iridectomy ( PI ) or Nd : YAG laser iridotomy ( YAG PI ) . METHODS A prospect i ve study of consecutive patients presenting to one ophthalmology department with uniocular AACG during a 2 year period . Following informed consent patients were r and omised to bilateral PI or bilateral YAG PI . Three years after treatment the mean Snellen visual acuity converted to logMAR scores of the two groups was compared using the unpaired Student ’s ttest . The number of patients with normal intraocular pressure with no further treatment in each group was compared using the χ2test with Yates ’s correction . RESULTS 21 patients underwent bilateral PI and 27 bilateral YAG PI . Three years after treatment visual acuity was 0.30 ( SD 0.28 ) log MAR units for PI eyes and 0.57 ( 0.67 ) logMAR units for YAG PI eyes ( p=0.08 , NS ) . 15 ( 70.4 % ) PI eyes and 19 ( 71.8 % ) YAG PI eyes had an intraocular pressure less than 21 mm Hg with no further treatment ( NS ) . CONCLUSIONS There was no significant difference in visual acuity or intraocular pressure control 3 years after treatment of AACG with PI or YAG PI PURPOSE Novel anterior segment optical coherence tomography ( ASOCT ) parameters associated with angle closure include anterior chamber area ( ACA ) , anterior chamber volume ( ACV ) , anterior chamber width ( ACW ) , lens vault ( LV ) , iris thickness ( IT ) , iris area ( I-area ) , and iris curvature ( I-curv ) . We aim ed to investigate changes in these parameters after laser peripheral iridotomy ( LPI ) in a cohort of primary angle-closure suspects ( PACS ) . DESIGN Prospect i ve observational study . PARTICIPANTS AND CONTROLS A total of 176 PACS aged ≥ 50 years who underwent LPI in 1 eye . METHODS We analyzed ASOCT images ( Visante , Carl Zeiss Meditec , Dublin , CA ) from all subjects using customized software before and 1 week after LPI . Multivariate linear regression analysis was performed for predictors of percentage change in mean angle opening distance ( AOD750 ) . MAIN OUTCOME MEASURES Change in ASOCT parameters after LPI . RESULTS The mean age of participants was 63 ± 7.3 years . The majority of subjects were Chinese ( 95.5 % ) and women ( 76.7 % ) . Mean angle width ( modified Shaffer grade ) changed from 0.68 ± 0.54 at baseline to 1.76±0.69 after LPI ( P<0.001 ) with a corresponding increase in mean AOD500 ( 0.12 vs. 0.19 mm , P<0.001 ) , trabecular iris surface area ( TISA500 , 0.06 vs. 0.08 mm(2 ) , P<0.001 ) , and angle recess area ( ARA , 0.13 vs. 0.17 mm(2 ) , P<0.001 ) . Mean ACA ( 15.0 vs. 16.0 mm(2 ) , P<0.001 ) and ACV ( 91.6 vs. 103.0 mm(3 ) , P<0.001 ) increased significantly after LPI , but there was no change in ACW , anterior chamber depth ( ACD ) , or LV . Mean I-curv was reduced ( 0.375 vs. 0.18 mm , P<0.001 ) after LPI , but there was no significant change in IT or I-area . After multivariate analysis , mean LV ( β = 0.286 , P = 0.001 ) , mean IT at 2000 μm ( IT2000 , β = 0.172 , P = 0.034 ) , and intraocular pressure ( β = 0.159 , P = 0.042 ) at baseline were found to be associated with ΔAOD750 . CONCLUSIONS This study confirms that LPI results in a significant increase in the angle width in PACS . The ACA and ACV increased after LPI , but there was no change in ACD , ACW , LV , IT , or I-area . The increase in ACA/ACV was mainly due to decreased I-curv after LPI PURPOSE To determine the prevalence of plateau iris in a cohort of primary angle closure suspects ( PACSs ) using ultrasound biomicroscopy ( UBM ) . DESIGN Cross-sectional observational study . PARTICIPANTS Subjects over the age of 50 years diagnosed as PACSs . INTERVENTION Subjects were r and omized to undergo laser peripheral iridotomy ( LPI ) in one eye . Ultrasound biomicroscopy was performed before and a week after LPI . MAIN OUTCOME MEASURES Ultrasound biomicroscopy images were qualitatively assessed using st and ardized criteria . Plateau iris was defined in a quadrant by the presence of an anteriorly directed ciliary body , an absent ciliary sulcus , a steep iris root from its point of insertion followed by a downward angulation from the corneoscleral wall , presence of a central flat iris plane , and irido-angle contact . At least 2 quadrants had to fulfil the above criteria for an eye to be defined as plateau iris . RESULTS Two hundred five subjects were enrolled ; UBM images of 167 subjects were available for analysis . Plateau iris was found in 54 of 167 ( 32.3 % ) PACS eyes after LPI . Quadrantwise analysis showed that 44 of 167 ( 26.3 % ) eyes had plateau iris in 1 quadrant , 36 ( 21.5 % ) in 2 quadrants , 16 ( 9.5 % ) in 3 quadrants , and 2 ( 1.2 % ) in all 4 quadrants . Plateau iris was most commonly observed in the superior and inferior quadrants . CONCLUSIONS Using st and ardized UBM criteria , plateau iris was found in about a third of PACS eyes after LPI . Prospect i ve longitudinal studies are required to determine the clinical significance of this finding for the management of PACSs Purpose : To summarize the design and methodology of a large-scale trial in southern China , the Zhongshan Angle Closure Prevention ( ZAP ) trial . This trial will determine if laser iridotomy ( LI ) is superior to no treatment for managing Chinese people who are Primary Angle Closure Suspects ( PACS ) . In this trial , PACS was defined as having 6 or more clock hours of angle circumference in which the pigmented trabecular meshwork was not visible under static gonioscopy in both eyes without elevated intraocular pressure , peripheral anterior synechiae or glaucomatous neuropathy . Methods : Subjects were recruited from an urban district in Guangzhou . The target sample size was 870 . Persons 50 years of age and older with 20/40 or better vision in both eyes identified as having 6 or more clock hours of angle circumference in which the pigmented trabecular meshwork was not visible under static gonioscopy in both eyes were enrolled . Each subject was r and omized to undergo LI in one eye with the fellow eye left untreated . Follow up is planned for a minimum period of 3 years . Baseline examination included tonometry , limbal chamber depth grading , gonioscopy , fundus photography , anterior segment coherence tomography , ultrasound A scan , ultrasound biomicroscopy , specular microscopy and dark room provocative testing . Endpoints for the study include developing elevated intraocular pressure , peripheral anterior synechiae or experiencing acute primary angle closure . Conclusion : The ZAP trial will determine if LI is safe and effective at preventing pathological angle closure in asymptomatic eyes with narrow angle configurations on gonioscopy . It will also provide data on what happens to untreated eyes in PACSs . Data collected at baseline will also help identify those at high risk for developing primary angle closure and primary angle closure glaucoma Aims To determine if screening with an ultrasound A-scan and prophylactic treatment of primary angle closure ( PAC ) with laser peripheral iridotomy ( LPI ) can reduce the incidence of primary angle closure glaucoma ( PACG ) in Mongolia . Methods A single-masked r and omised controlled trial was initiated in 1999 . 4725 volunteer Mongolian participants ≥50 years old from the capital Ulaanbaatar or the rural province of Bayankhongor were recruited , of which 128 were excluded with glaucoma . 4597 were r and omly allocated to the control , no-screening arm or screening with ultrasound central anterior chamber depth ( cACD ) , with the cut-off set at < 2.53 mm . 685 screen-positive participants were examined and angle closure was identified by gonioscopy in 160 , of which 156 were treated with prophylactic LPI . Primary outcome of incident PACG was determined using both structural and functional evidence from objective grading of paired disc photographs from baseline and follow-up , objective grading of follow-up visual fields and clinical examination . Results Six years later , 801 ( 17.42 % ) participants were known to have died , and a further 2047 ( 53.92 % ) were traced and underwent full ophthalmic examination . In an intention to treat analysis using available data , PACG was diagnosed in 33 participants ( 1.61 % , 95 % CI 1.11 % to 2.25 % ) , of which 19 were in the screened group and 14 in the non-screened group ( OR 1.29 , 95 % CI 0.65 to 2.60 , p=0.47 ) , indicating no difference between groups . Conclusions We were not able to identify a reduction in the 6 year incidence of PACG after screening with cACD < 2.53 mm and prophylactic treatment of PAC PURPOSE To assess the immediate effect of laser peripheral ir Output:	At present , we can not draw reliable conclusions based on r and omized controlled trials as to whether iridotomy slows progression of visual field loss at one year compared to no iridotomy . Full publication of the results from the studies may clarify the benefits of iridotomy
MS22113	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Age‐related endothelial dysfunction and vascular stiffening are associated with increased cardiovascular ( CV ) risk . Many groups have encouraged goals of ≥10 000 steps/day or ≥30 min/day of moderate intensity physical activity ( MPA ) to reduce age‐related CV risk . The impact of MPA on the vasculature of older adults remains unclear . Methods and Results We r and omized 114 sedentary older adults ages ≥50 to 12 weeks of either no intervention ( group 1 ) , a pedometer‐only intervention ( group 2 ) , or a pedometer with an interactive website employing strategies to increase the adoption of habitual physical activity ( PA , group 3 ) . Endothelial function by brachial flow‐mediated dilation ( FMD% ) , vascular stiffness by tonometry , step‐count by pedometer , and PA intensity/distribution by accelerometer were measured . Step‐count increased in groups 2 ( 5136±1554 to 9596±3907 , P<0.001 ) and 3 ( 5474±1512 to 8167±3111 , P<0.001 ) but not in group 1 ( 4931±1667 to 5410±2410 ) . Both groups 2 and 3 increased MPA ≥30 min/day . Only group 3 increased MPA in continuous bouts of ≥10 minutes ( P<0.001 ) and improved FMD% ( P=0.001 ) . Neither achievement of ≥10 000 steps/day nor ≥30 min/day of MPA result ed in improved FMD% . However , achieving ≥20 min/day in MPA bouts result ed in improved FMD% . No changes in vascular stiffness were observed . Conclusions MPA reverses age‐related endothelial dysfunction , but may require MPA to be performed in bouts of ≥10 minutes duration for ≥20 min/day to be effective . Commonly encouraged PA goals do not guarantee improved endothelial function and may not be as effective in reducing CV risk . Clinical Trial Registration URL : Clinical trials.gov . Unique identifier : NCT‐01212978 Background Self – reported physical activity has been inversely associated with mortality but the effect of objective ly measured step activity on mortality has never been evaluated . The objective is to determine the prospect i ve association of daily step activity on mortality among free-living adults . Methods and Findings Cohort study of free-living adults residing in Tasmania , Australia between 2000 and 2005 who participated in one of three cohort studies ( n = 2 576 total participants ) . Daily step activity by pedometer at baseline at a mean of 58.8 years of age , and for a subset , repeated monitoring was available 3.7 ( SD 1.3 ) years later ( n = 1 679 ) . All-cause mortality ( n = 219 deaths ) was ascertained by record-linkage to the Australian National Death Index ; 90 % of participants were followed-up over ten years , until June 2011 . Higher daily step count at baseline was linearly associated with lower all-cause mortality ( adjusted hazard ratio AHR , 0.94 ; 95 % CI , 0.90 to 0.98 per 1 000 steps ; P = 0.004 ) . Risk was altered little by removing deaths occurring in the first two years . Increasing baseline daily steps from sedentary to 10 000 steps a day was associated with a 46 % ( 95 % CI , 18 % to 65 % ; P = 0.004 ) lower risk of mortality in the decade of follow-up . In addition , those who increased their daily steps over the monitoring period had a substantial reduction in mortality risk , after adjusting for baseline daily step count ( AHR , 0.39 ; 95 % CI , 0.22 to 0.72 ; P = 0.002 ) , or other factors ( AHR , 0.38 ; 95 % CI , 0.21–0.70 ; P = 0.002 ) . Conclusions Higher daily step count was linearly associated with subsequent long term mortality among free living adults . These data are the first to quantify mortality reductions using an objective measure of physical activity in a free living population . They strongly underscore the importance of physical inactivity as a major public health problem Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Being overweight is associated with vascular abnormalities , which are important in the development of atherosclerosis . However , little is known about dietary and lifestyle determinants of vascular function in overweight children . In adults , dietary protein and milk intake are associated with reduced blood pressure and reduced risk of metabolic syndrome . This study examined the associations between dietary protein , milk intake , physical activity , and adiposity on arterial stiffness in overweight children . In a cross-sectional study , overweight children with habitual milk intakes ≤ 250 mL/d were examined by DXA scans , pedometer counts , anthropometry , and metabolic variables . Dietary intake was registered for 4 d. The outcomes were arterial stiffness measured by pulse wave velocity ( PWV ) ( n = 182 ) and augmentation index ( Aix ) ( n = 183 ) . The PWV ( mean ± SD ) was 4.78 ± 0.72 m/s and the Aix was -0.77 ± 9.44 % . In multivariate models , the and roid fat : gynoid fat and and roid fat : body fat ratios were positively associated with PWV ( β = 1.49 and β = 10.3 , both P < 0.05 ) and Aix ( β = 28.3 , P < 0.01 and β = 153 , P < 0.05 ) , whereas the gynoid fat : body fat ratio was negatively associated with the Aix ( β = -134 ; P < 0.001 ) . Protein intake ( percentage energy ) was positively associated with PWV ( β = 0.05 ; P < 0.01 ) . Milk intake ( L/d ) tended to be negatively associated with PWV ( β = -0.64 ; P = 0.05 ) . Pedometer counts were negatively associated with the Aix ; however , the association became nonsignificant after controlling for HOMA , which was positively associated with the Aix ( β = 0.95 ; P < 0.01 ) . In conclusion , central adiposity and protein intake are associated with increased arterial stiffness measured as PWV in overweight children independent of blood pressure and heart rate . The effect of protein intake may be caused by meat , because the milk intake was low Background New technologies could facilitate changes in lifestyle and improve public health . However , no large r and omized , controlled studies providing scientific evidence of the benefits of their use have been made . The aims of this study are to develop and vali date a smartphone application , and to evaluate the effect of adding this tool to a st and ardized intervention design ed to improve adherence to the Mediterranean diet and to physical activity . An evaluation is also made of the effect of modifying habits upon vascular structure and function , and therefore on arterial aging . Methods / Design A r and omized , double-blind , multicenter , parallel group clinical trial will be carried out . A total of 1215 subjects under 70 years of age from the EVIDENT trial will be included . Counseling common to both groups ( control and intervention ) will be provided on adaptation to the Mediterranean diet and on physical activity . The intervention group moreover will receive training on the use of a smartphone application design ed to promote a healthy diet and increased physical activity , and will use the application for three months . The main study endpoints will be the changes in physical activity , assessed by accelerometer and the 7-day Physical Activity Recall ( PAR ) interview , and adaptation to the Mediterranean diet , as evaluated by an adherence question naire and a food frequency question naire ( FFQ ) . Evaluation also will be made of vascular structure and function based on central arterial pressure , the radial augmentation index , pulse velocity , the cardio-ankle vascular index , and carotid intima-media thickness . Discussion Confirmation that the new technologies are useful for promoting healthier lifestyles and that their effects are beneficial in terms of arterial aging will have important clinical implication s , and may contribute to generalize their application in favor of improved population health . Trial registration Clinical Trials.gov Identifier : CONTEXT Persuasive evidence has demonstrated that increased physical activity is associated with substantial reduction in risk of coronary heart disease . However , the role of physical activity in the prevention of stroke is less well established . OBJECTIVE To examine the association between physical activity and risk of total stroke and stroke subtypes in women . DESIGN AND SETTING The Nurses ' Health Study , a prospect i ve cohort study of subjects residing in 11 US states . SUBJECTS A total of 72,488 female nurses aged 40 to 65 years who did not have diagnosed cardiovascular disease or cancer at baseline in 1986 and who completed detailed physical activity question naires in 1986 , 1988 , and 1992 . MAIN OUTCOME MEASURE Incident stroke occurring between baseline and June 1 , 1994 , compared among quintiles of physical activity level as measured by metabolic equivalent tasks ( METs ) in hours per week . RESULTS During 8 years ( 560,087 person-years ) of follow-up , we documented 407 incident cases of stroke ( 258 ischemic strokes , 67 subarachnoid hemorrhages , 42 intracerebral hemorrhages , and 40 strokes of unknown type ) . In multivariate analyses controlling for age , body mass index , history of hypertension , and other covariates , increasing physical activity was strongly inversely associated with risk of total stroke . Relative risks ( RRs ) in the lowest to highest MET quintiles were 1 . 00 , 0.98 , 0.82 , 0.74 , and 0.66 ( P for trend=.005 ) . The inverse gradient was seen primarily for ischemic stroke ( RRs across increasing MET quintiles , 1.00 , 0.87 , 0.83 , 0.76 , and 0.52 ; P for trend=.003 ) . Physical activity was not significantly associated with subarachnoid hemorrhage or intracerebral hemorrhage . After multivariate adjustment , walking was associated with reduced risk of total stroke ( RRs across increasing walking MET quintiles , 1.00 , 0 . 76 , 0.78 , 0.70 , and 0.66 ; P for trend=.01 ) and ischemic stroke ( RRs across increasing walking MET quintiles , 1.00 , 0.77 , 0.75 , 0.69 , and 0.60 ; P for trend=.02 ) . Brisk or striding walking pace was associated with lower risk of total and ischemic stroke compared with average or casual pace . CONCLUSION These data indicate that physical activity , including moderate-intensity exercise such as walking , is associated with substantial reduction in risk of total and ischemic stroke in a dose-response manner . JAMA . 2000 Background : Physical activity ( PA ) is inversely associated with obesity but the effect has been difficult to quantify using question naires . In particular , the shape of the association has not yet been well described . Pedometers provide an opportunity to better characterize the association . Methods : Residents of households over the age of 25 years in r and omly selected census districts in Tasmania were eligible to participate in the AusDiab cross-sectional survey conducted in 1999–2000 . 1848 completed the AusDiab survey and 1126 of these ( 609 women and 517 men ) wore a pedometer for 2-weekdays . Question naire data on recent PA , TV time and other factors were obtained . The outcomes were waist circumference ( in cm ) and body mass index ( BMI ) ( kg/m2 ) . Results : Increasing daily steps were associated with a decline in the obesity measures . The logarithmic nature of the associations was indicated by a sharper decline for those with lower daily steps . For example , an additional 2000 steps for those taking only 2000 steps per day was associated with a reduction of 2.8 ( 95 % confidence interval ( CI ) : 2.1,4.4 ) cm in waist circumference among men ( for women ; 2.2 ( 95 % CI : 0.6 , 3.9 cm ) ) with a baseline of only 2000 , steps compared to a 0.7 ( 95 % CI 0.3 , 1.1 ) cm reduction ( for women ; 0.6 ( 95 % CI : 0.2 , 1.0 ) ) for those already walking 10 000 steps daily . In the multivariable analysis , clearer associations were detected for PA and these obesity measures using daily step number rather than PA time by question naire . Interpretation : Pedometer measures of activity indicate that the inverse association between recent PA and obesity is logarithmic in form with the greatest impact for a given arithmetic step number increase seen at lower levels of baseline activity . The findings from this study need to be examined in prospect i ve setting The central arteries stiffen with age , causing hemodynamic alterations that have been associated with cardiovascular events . Changes in body fat with age may be Output:	This systematic review and meta- analysis demonstrates a clinical ly meaningful association between objective ly monitored steps per day and PWv , an accepted indicator of arterial stiffness and an early sub clinical risk factor for cardiovascular disease .
MS22114	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: INTRODUCTION The aim of this study was to determine the safety and therapeutic potential of L-carnitine and valproic acid ( VPA ) in infants with spinal muscular atrophy ( SMA ) . METHODS Our investigation was an open-label phase 2 multicenter trial of L-carnitine and VPA in infants with SMA type I with retrospective comparison to an untreated , matched cohort . Primary outcomes were : safety and adverse events ; secondary outcomes were survival , time to death/>16 hours/day of ventilator support ; motor outcomes ; and maximum ulnar compound motor action potential amplitude . RESULTS A total of 245 AEs were observed in 35 of the 37 treated subjects ( 95 % ) . Respiratory events accounted for 49 % of all adverse events , result ing in 14 deaths . Survival was not significantly different between treated and untreated cohorts . DISCUSSION This trial provides evidence that , in infants with SMA type I , L-carnitine/VPA is ineffective at altering survival . The substantial proportion of infants reaching end-points within 6 months of enrollment underscores the urgent need for pre-symptomatic treatment in SMA type I. Muscle Nerve 57 : 193 - 199 , 2018 Background Valproic acid ( VPA ) has demonstrated potential as a therapeutic c and i date for spinal muscular atrophy ( SMA ) in vitro and in vivo . Methods Two cohorts of subjects were enrolled in the SMA CARNIVAL TRIAL , a non-ambulatory group of “ sitters ” ( cohort 1 ) and an ambulatory group of “ walkers ” ( cohort 2 ) . Here , we present results for cohort 1 : a multicenter phase II r and omized double-blind intention-to-treat protocol in non-ambulatory SMA subjects 2–8 years of age . Sixty-one subjects were r and omized 1∶1 to placebo or treatment for the first six months ; all received active treatment the subsequent six months . The primary outcome was change in the modified Hammersmith Functional Motor Scale ( MHFMS ) score following six months of treatment . Secondary outcomes included safety and adverse event data , and change in MHFMS score for twelve versus six months of active treatment , body composition , quantitative SMN mRNA levels , maximum ulnar CMAP amplitudes , myometry and PFT measures . Results At 6 months , there was no difference in change from the baseline MHFMS score between treatment and placebo groups ( difference = 0.643 , 95 % CI = −1.22–2.51 ) . Adverse events occurred in > 80 % of subjects and were more common in the treatment group . Excessive weight gain was the most frequent drug-related adverse event , and increased fat mass was negatively related to change in MHFMS values ( p = 0.0409 ) . Post-hoc analysis found that children ages two to three years that received 12 months treatment , when adjusted for baseline weight , had significantly improved MHFMS scores ( p = 0.03 ) compared to those who received placebo the first six months . A linear regression analysis limited to the influence of age demonstrates young age as a significant factor in improved MHFMS scores ( p = 0.007 ) . Conclusions This study demonstrated no benefit from six months treatment with VPA and L-carnitine in a young non-ambulatory cohort of subjects with SMA . Weight gain , age and treatment duration were significant confounding variables that should be considered in the design of future trials . Trial Registry Clinical trials.gov Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Background Spinal muscular atrophy ( SMA ) is an autosomal recessive disorder that affects the motoneurons of the spinal anterior horn , result ing in hypotonia and muscle weakness . The disease is caused by deletion or mutation in the telomeric copy of SMN gene ( SMN1 ) and clinical severity is in part determined by the copy number of the centromeric copy of the SMN gene ( SMN2 ) . The SMN2 mRNA lacks exon 7 , result ing in a production of lower amounts of the full-length SMN protein . Knowledge of the molecular mechanism of diseases has led to the discovery of drugs capable of increasing SMN protein level through activation of SMN2 gene . One of these drugs is the valproic acid ( VPA ) , a histone deacetylase inhibitor . Methods Twenty-two patients with type II and III SMA , aged between 2 and 18 years , were treated with VPA and were evaluated five times during a one-year period using the Manual Muscle Test ( Medical Research Council scale-MRC ) , the Hammersmith Functional Motor Scale ( HFMS ) , and the Barthel Index . Results After 12 months of therapy , the patients did not gain muscle strength . The group of children with SMA type II presented a significant gain in HFMS scores during the treatment . This improvement was not observed in the group of type III patients . The analysis of the HFMS scores during the treatment period in the groups of patients younger and older than 6 years of age did not show any significant result . There was an improvement of the daily activities at the end of the VPA treatment period . Conclusion Treatment of SMA patients with VPA may be a potential alternative to alleviate the progression of the disease . Trial Registration Clinical Trials.gov : Non-r and omised studies of the effects of interventions are critical to many areas of healthcare evaluation , but their results may be biased . It is therefore important to underst and and appraise their strengths and weaknesses . We developed ROBINS-I ( “ Risk Of Bias In Non-r and omised Studies - of Interventions ” ) , a new tool for evaluating risk of bias in estimates of the comparative effectiveness ( harm or benefit ) of interventions from studies that did not use r and omisation to allocate units ( individuals or clusters of individuals ) to comparison groups . The tool will be particularly useful to those undertaking systematic review s that include non-r and omised studies Background Multiple lines of evidence have suggested that valproic acid ( VPA ) might benefit patients with spinal muscular atrophy ( SMA ) . The SMA CARNIVAL TRIAL was a two part prospect i ve trial to evaluate oral VPA and l-carnitine in SMA children . Part 1 targeted non-ambulatory children ages 2–8 in a 12 month cross over design . We report here Part 2 , a twelve month prospect i ve , open-label trial of VPA and L-carnitine in ambulatory SMA children . Methods This study involved 33 genetically proven type 3 SMA subjects ages 3–17 years . Subjects underwent two baseline assessment s over 4–6 weeks and then were placed on VPA and L-carnitine for 12 months . Assessment s were performed at baseline , 3 , 6 and 12 months . Primary outcomes included safety , adverse events and the change at 6 and 12 months in motor function assessed using the Modified Hammersmith Functional Motor Scale Extend ( MHFMS-Extend ) , timed motor tests and fine motor modules . Secondary outcomes included changes in ulnar compound muscle action potential amplitudes ( CMAP ) , h and held dynamometry , pulmonary function , and Pediatric Quality of Life Inventory scores . Results Twenty-eight subjects completed the study . VPA and carnitine were generally well tolerated . Although adverse events occurred in 85 % of subjects , they were usually mild and transient . Weight gain of 20 % above body weight occurred in 17 % of subjects . There was no significant change in any primary outcome at six or 12 months . Some pulmonary function measures showed improvement at one year as expected with normal growth . CMAP significantly improved suggesting a modest biologic effect not clinical ly meaningful . Conclusions This study , coupled with the CARNIVAL Part 1 study , indicate that VPA is not effective in improving strength or function in SMA children . The outcomes used in this study are feasible and reliable , and can be employed in future trials in SMA . Trial Regsitration Clinical trials.gov Preliminary in vitro and in vivo studies with valproic acid ( VPA ) in cell lines and patients with spinal muscular atrophy ( SMA ) demonstrate increased expression of SMN , supporting the possibility of therapeutic benefit . We performed an open label trial of VPA in 42 subjects with SMA to assess safety and explore potential outcome measures to help guide design of future controlled clinical trials . Subjects included 2 SMA type I ages 2–3 years , 29 SMA type II ages 2–14 years and 11 type III ages 2–31 years , recruited from a natural history study . VPA was well-tolerated and without evident hepatotoxicity . Carnitine depletion was frequent and temporally associated with increased weakness in two subjects . Exploratory outcome measures included assessment of gross motor function via the modified Hammersmith Functional Motor Scale ( MHFMS ) , electrophysiologic measures of innervation including maximum ulnar compound muscle action potential ( CMAP ) amplitudes and motor unit number estimation ( MUNE ) , body composition and bone density via dual-energy X-ray absorptiometry ( DEXA ) , and quantitative blood SMN mRNA levels . Clear decline in motor function occurred in several subjects in association with weight gain ; mean fat mass increased without a corresponding increase in lean mass . We observed an increased mean score on the MHFMS scale in 27 subjects with SMA type II ( p≤0.001 ) ; however , significant improvement was almost entirely restricted to participants < 5 years of age . Full length SMN levels were unchanged and Δ7SMN levels were significantly reduced for 2 of 3 treatment visits . In contrast , bone mineral density ( p≤0.0036 ) and maximum ulnar CMAP scores ( p≤0.0001 ) increased significantly . Conclusions While VPA appears safe and well-tolerated in this initial pilot trial , these data suggest that weight gain and carnitine depletion are likely to be significant confounding factors in clinical trials . This study highlights potential strengths and limitations of various c and i date outcome measures and underscores the need for additional controlled clinical trials with VPA targeting more restricted cohorts of subjects . Trial Registration Clinical Abstract Background : Clinical trials of therapies for spinal muscular atrophy ( SMA ) that are design ed to increase the expression the SMN protein ideally include careful assessment of relevant SMN biomarkers . Objective : In the SMA VALIANT trial , a recent double-blind placebo-controlled crossover study of valproic acid ( VPA ) in ambulatory adult subjects with SMA , we investigated relevant pharmacodynamic biomarkers in blood sample s from SMA subjects by direct longitudinal measurement of histone acetylation and SMN mRNA and protein levels in the presence and absence of VPA treatment . Methods : Thirty-three subjects were r and omized to either VPA or placebo for the first 6 months followed by crossover to the opposite arm for an additional 6 months . Outcome measures were compared between the two treatments ( VPA and placebo ) using a st and ard crossover analysis . Results : A significant increase in histone H4 acetylation was observed with VPA treatment ( p = 0.005 ) . There was insufficient evidence to suggest a treatment effect with either full length or truncated SMN mRNA transcript levels or SMN protein levels . Conclusions : These measures were consistent with the observed lack of change in the primary clinical outcome measure in the VALIANT trial . These results also highlight the added benefit of molecular and pharmacodynamic biomarker measurements in the interpretation of clinical trial outcomes INTRODUCTION An open-label trial suggested that valproic acid ( VPA ) improved strength in adults with spinal muscular atrophy ( SMA ) . We report a 12-month , double-blind , cross-over study of VPA in ambulatory SMA adults . METHODS There were 33 subjects , aged 20–55 years , included in this investigation . After baseline assessment , subjects were r and omized to receive VPA ( 10–20 mg/kg/day ) or placebo . At 6 months , patients were switched to the other group . Assessment s were performed at 3 , 6 , and 12 months . The primary outcome was the 6-month change in maximum voluntary isometric contraction testing with pulmonary , electrophysiological , and functional secondary outcomes . RESULTS Thirty subjects completed the study . VPA was well tolerated , and compliance was good . There was no change in primary or secondary outcomes at 6 or 12 months . CONCLUSIONS VPA did not improve strength or function in SMA adults . The outcomes used are feasible and reliable and can be employed in future trials in SMA adults Spinal muscular atrophy results from loss of the survival motor neuron 1 ( SMN1 ) gene and malfunction of the remaining SMN2 . We investigated whether valproic acid can elevate human SMN expression in vivo BACKGROUND Nusinersen is a 2'-O-methoxyethyl phosphorothioate-modified antisense drug being developed to treat spinal muscular atrophy . Nusinersen is specifically design ed to alter splicing of SMN2 pre-mRNA and thus increase the amount of functional survival motor neuron ( SMN ) protein that is deficient in patients with spinal muscular atrophy . METHODS This open-label , phase 2 , escalating dose clinical study assessed the safety and tolerability , pharmacokinetics , and clinical efficacy of multiple intrathecal doses of nusinersen ( 6 mg and 12 mg dose equivalents ) in patients with infantile-onset spinal muscular atrophy . Eligible participants were of either gender aged between 3 weeks and 7 months old with onset of spinal muscular atrophy symptoms between 3 weeks and 6 months , who had SMN1 homozygous Output:	Qualitative synthesis showed that other motor functions were not improved , while respiratory function test results were contradictory . Moreover , most of the included studies reported no serious AEs related to VPA use , although weight gain , gastrointestinal symptoms and respiratory symptoms were notable problems . Conclusions Our study suggests that VPA treatment results in an improvement in gross motor functions for SMA patients , but not in other assessment s of motor function or , possibly , in respiratory function . Furthermore , VPA appears to be a relatively safe drug , although treatment may be associated with a wide range of AEs ( including body weight increase , fatigue , fever , flu-like symptoms , irritability , and pain ) .
MS22115	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND This study examines the effectiveness of a nursing home staff training program design ed to improve the interaction between residents with dementia and their caregivers . METHODS A three-arm cluster-r and omized and controlled population of 96 caregivers and 210 residents was used . Caregivers of the intervention group ( IG ) received a three-month training program in dementia care . Data were gathered at baseline , immediately after the training and at a six-month follow-up- assessment . Short- and long-term effects of the training program were assessed in comparison with another intervention referred to as the relaxation group ( RG ) and a wait-list control group ( CG ) . RESULTS Results indicated significant positive effects of the training program on caregivers ' knowledge immediately after the training and on the use of physical restraints at the six-month follow-up . Caregivers ' overall competence increased significantly both in the IG and in the RG . No intervention effects were found on caregivers ' level of burnout , their health complaints or on the use of sedative drugs . Relaxation training was more successful in the reduction of caregivers ' health complaints . CONCLUSIONS Results of the study indicate both the effectiveness and the limitations of a general training program in dementia care . The complexity of the nursing home setting potentially needs more complex interventions . Ongoing and continued support of the caregivers , as well as changes in organization and environment , are more likely to be helpful in the long-term improvement in the quality of care . Future research should focus on studies of specific interventions , such as the interesting effects of relaxation training on the caregivers ' state of health WHAT IS KNOWN ON THE SUBJECT ? : To stimulate reminiscence of older adults with dementia performed individually or through group sessions is a well-known practice in nursing homes result ing in effects on behaviour and well-being as an alternative for medication . Robust scientific proof of the effectiveness of individual reminiscence therapy performed in nursing homes is sparse . WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE ? : We have provided individual st and ardized reminiscence therapy to residents with dementia . The therapy was developed and tested in a previous study and performed in this study by trained nursing home volunteers . In comparison with a control group who received usual care , residents who received the reminiscence therapy showed significant less depressive symptoms . Moreover , residents were , in general , attentive , open and collaborative during the sessions and volunteers experienced the sessions as useful and pleasant . WHAT ARE THE IMPLICATION S FOR PRACTICE ? : Individual reminiscence therapy can be learned and used by nursing home volunteers to improve care in nursing homes . ABSTRACT Aim To investigate the effect of a st and ardized individualized intervention based on the SolCos transformational reminiscence model on depressive symptoms ( primary outcome ) , cognition and behaviour ( secondary outcomes ) for older people with mild to moderate dementia , performed by trained nursing home volunteers as facilitators . Background Because of limited pharmacological treatment options for older adults with dementia relevant physical , sensory , psychological or social interventions offer alternative opportunities . Method R and omized controlled trial ( IS RCT N74355073 ) was set up in two nursing homes with 29 and 31 residents in the intervention and the control groups respectively . Eighteen nursing home volunteers were trained to perform the reminiscence therapy . Various assessment scales were measured pre- and post-sessions . Results Linear regression analysis showed an impact on depressive symptoms . However , no impact was identified on cognition and behaviour . Facilitators experienced the sessions as useful and pleasant , and study participants were , in general , attentive , open and collaborative . Discussion Study results showed that organizing st and ardized individual reminiscence therapy with nursing home volunteers was feasible and study participants ' attention and participation were overall good . Further study initiatives to explore the potential of individual reminiscence therapy within a person-centred framework are recommended in order to improve care in nursing homes BACKGROUND Elderly people with cognitive impairments are often associated with depressed mood and are heavy consumers in both medical services and need in caregivers . Reminiscence is believed to be effective in improving the cognition and mood of demented people . OBJECTIVES This study tested the hypothesis that structured group reminiscence therapy can prevent the progression of cognitive impairment and enhance affective function in the cognitively impaired elderly . METHODS A r and omized controlled trial ( RCT ) based on a two group pre- and post-test design was used . The experimental subjects underwent eight group sessions , one session per week . The measurements were performed using Mini-Mental State Examination ( MMSE ) , Geriatric Depression Scale short form ( GDS-SF ) , and Cornell Scale for Depression in Dementia ( CSDD ) . RESULTS The sample consisted of 102 subjects , with 51 in the experimental group and 51 in the control group . Results demonstrated that the intervention significantly affected cognitive function and affective function as measured by MMSE and CSDD ( p = 0.015 and 0.026 ) , indicating that the cognitive function of the experimental subjects increased and their depressive symptoms diminished following intervention . CONCLUSION Participation in reminiscence activities can be a positive and valuable experience for demented older persons . Consequently , the development of a structured care program for elderly persons with cognitive impairment and the need for long-term care is essential . Thus , health providers in long-term care facilities should be trained in reminiscence group therapy , and to be able to deliver such a program to the targeted group The purpose of this study was , conducted with experimental design , to investigate the effect of reminiscence therapy on cognition , depression , activities of daily living of institutionalized mild and moderate Alzheimer patients . The study was conducted with a total of 62 patients ( 31 intervention group and 31 control group ) in four home care in Ankara , Turkey . Study was done between the July 1 , 2013 and December 20 , 2014 . Reminiscence therapy sessions were held with groups consists of 4 - 5 patients , once a week with 30 - 35 minute duration for 12 weeks . St and ardized Mini Mental Test was used in sample selection . Patients were listed through their mini mental test scores , and r and omized as odd numbers to control group and even numbers to intervention group . Data were collected with forms developed by research er ‘ Data Sheet ’ and ‘ Activities of Daily Living Follow-up Form ’ as well as scales ‘ St and ardized Mini Mental Test ’ and ‘ Geriatric Depression Scale ’ . Chi-square , Mann Whitney-U test , variance analyses in repeated measures and Bonferroni tests were used for analysis . The increase in mean St and ardized Mini Mental Test score and the decrease in mean Geriatric Depression Scale score of the individuals in the intervention group compared to the control group at the end of the reminiscence therapy was statistically significant ( P < 0.05 ) . At the end of reminiscence therapy sessions , increase in cognition and decrease in depression were found statistically significant in intervention group Output:	CONCLUSION Reminiscence Therapy has potential efficacy for maintaining cognition and decrease of depressive symptomatology in the target population
MS22116	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Ninety-seven patients with insulin dependent diabetes mellitus ( IDDM ) were r and omized to intensified conventional treatment ( ICT , n = 44 ) or regular treatment ( RT , n = 53 ) . The mean HbA1c level ( + /- SEM ) was reduced from 9.5 + /- 0.2 % to 7.4 + /- 0.1 % in the ICT group ( P less than 0.001 ) , and from 9.4 + /- 0.2 % to 9.0 + /- 0.2 % ( P less than 0.01 ) in the RT group . The difference between the groups was significant ( P less than 0.001 ) . During a period of 3 years , 57 % of the ICT patients ( 95 % confidence interval 44 - 73 % ) and 23 % of the RT patients ( 95 % CI , 11 - 34 % ) ( P less than 0.001 ) had at least one episode of serious hypoglycaemia , with the need for third-party assistance or result ing in coma . Eighteen of the 32 ICT patients who initially had adrenergic symptoms during hypoglycaemia changed to predominantly neuroglycopenic symptoms . This was the case with only 8 of 38 RT patients ( P less than 0.01 ) . The change in symptoms was related to the increased frequency of serious hypoglycaemia , but neither symptoms nor frequency of hypoglycaemia bor any relationship to insulin dose , body mass index , duration of diabetes or autonomic nerve function . The results of several neuropsychological tests did not differ between the groups at baseline , and did not change during the study . There were no signs of deteriorating cognitive function in the patients with serious hypoglycaemic episodes OBJECTIVE —In this study , we used neurocognitive assessment and neuroimaging to examine brain function in youth with type 1 diabetes studied prospect ively from diagnosis . RESEARCH DESIGN AND METHODS —We studied type 1 diabetic ( n = 106 ) and control subjects ( n = 75 ) with no significant group difference on IQ at baseline 12 years previously by using the Wechsler Abbreviated Scale of General Intelligence , magnetic resonance spectroscopy and imaging , and metabolic control data from diagnosis . RESULTS —Type 1 diabetic subjects had lower verbal and full scale IQs than control subjects ( both P < 0.05 ) . Type 1 diabetic subjects had lower N-acetylaspartate in frontal lobes and basal ganglia and higher myoinositol and choline in frontal and temporal lobes and basal ganglia than control subjects ( all P < 0.05 ) . Type 1 diabetic subjects , relative to control subjects , had decreased gray matter in bilateral thalami and right parahippocampal gyrus and insular cortex . White matter was decreased in bilateral parahippocampi , left temporal lobe , and middle frontal area ( all P < 0.0005 uncorrected ) . T2 in type 1 diabetic subjects was increased in left superior temporal gyrus and decreased in bilateral lentiform nuclei , cau date nuclei and thalami , and right insular area ( all P < 0.0005 uncorrected ) . Early-onset disease predicted lower performance IQ , and hypoglycemia was associated with lower verbal IQ and volume reduction in thalamus ; poor metabolic control predicted elevated myoinositol and decreased T2 in thalamus ; and older age predicted volume loss and T2 change in basal ganglia . CONCLUSIONS —This study documents brain effects 12 years after diagnosis in a type 1 diabetic sample whose IQ at diagnosis matched that of control subjects . Findings suggest several neuropathological processes including gliosis , demyelination , and altered osmolarity Background Prospect i ve memory is that memory which is required to carry out intended actions and is therefore essential in carrying out the daily activities required in the self-management of type 1 diabetes mellitus ( T1DM ) . This study aim ed to identify the relationships between prospect i ve memory and diabetic control in children with T1DM . Method 94 children aged 6–18 years with T1DM completed an innovative prospect i ve memory screen , PROMS , and a series of cognitive tests . Parents answered question naires about their children 's diabetic histories and cognitive skills . Results No association between total PROMS score and glycemic control was found . Lower HbA1C was associated with higher ( better ) scores on the 20 minute event-based task on the PROMS . Parental concerns about working memory and metacognition in their children were mirrored by higher HbA1C . Conclusions This study suggests that there may be an association between glycemic control and prospect i ve memory for event based tasks . Additional studies need to be done to determine reproducibility , causality , and if prospect i ve memory based interventions can improve diabetic control Declining incidences in Europe of overt nephropathy , proliferative retinopathy , and mortality in type 1 diabetes have recently been reported . However , comparable data for the U.S. and trend data for neuropathy and macrovascular complications are lacking . These issues are addressed using the prospect i ve observational Pittsburgh Epidemiology of Childhood-Onset Diabetes Complications Study . Participants were stratified into five cohorts by diagnosis year : 1950–1959 , 1960–1964 , 1965–1969 , 1970–1974 , and 1975–1980 . Mortality , renal failure , and coronary artery disease ( CAD ) status were determined on the complete cohort ( n = 906 ) at 20 , 25 , and 30 years . Overt nephropathy , proliferative retinopathy , and neuropathy were assessed at 20 and 25 years on the subset of participants with a clinical examination . There was a decreasing trend by diagnosis year for mortality , renal failure , and neuropathy across all time intervals ( P < 0.05 ) , with the 1950–1959 cohort having a fivefold higher mortality at 25 years than the 1970s ’ cohorts . Proliferative retinopathy and overt nephropathy showed nonsignificant declines at 20 years ( P < 0.16 and P < 0.13 , respectively ) and no change at 25 years . CAD event rates , which were lower than the other complications , also showed no trend . Although some type 1 diabetes complications ( mortality , renal failure , and neuropathy ) are declining , others ( CAD , overt nephropathy , and proliferative retinopathy ) show less favorable changes by 30 years OBJECTIVE —The purpose of this study was to evaluate whether severe hypoglycemia or intensive therapy affects cognitive performance over time in a subgroup of patients who were aged 13–19 years at entry in the Diabetes Control and Complications Trial ( DCCT ) . RESEARCH DESIGN AND METHODS —This was a longitudinal study involving 249 patients with type 1 diabetes who were between 13 and 19 years old when they were r and omly assigned in the DCCT . Scores on a comprehensive battery of cognitive tests obtained during the Epidemiology of Diabetes Interventions and Complications follow-up study , ∼18 years later , were compared with baseline performance . We assessed the effects of the original DCCT treatment group assignment , mean A1C values , and frequency of severe hypoglycemic events on eight domains of cognition . RESULTS —There were a total of 294 reported episodes of coma or seizure . Neither frequency of hypoglycemia nor previous treatment group was associated with decline on any cognitive domain . As in a previous analysis of the entire study cohort , higher A1C values were associated with declines in the psychomotor and mental efficiency domain ( P < 0.01 ) ; however , the previous finding of improved motor speed with lower A1C values was not replicated in this subgroup analysis . CONCLUSIONS —Despite relatively high rates of severe hypoglycemia , cognitive function did not decline over an extended period of time in the youngest cohort of patients with type 1 diabetes BACKGROUND Lowered neuropsychological performance is evident in youth with type 1 diabetes , although evidence for associations with specific illness variables is inconsistent . This study examined the neuropsychological profiles of a cohort of youth with type 1 diabetes studied prospect ively from diagnosis 12 yr previously . METHODS A total of 106 youth with type 1 diabetes and 75 healthy controls participated . There were no significant group differences on Full-scale IQ assessed on study entry 12 yr previously , current socioeconomic status , gender distribution , or age . Neuropsychological tests assessed eight cognitive domains : verbal abilities , perceptual reasoning , new learning , working memory , non-verbal processing speed , mental efficiency , divided attention , and sustained attention . Episodes of serious hypoglycemia and HbA(1c ) levels were recorded from diagnosis . RESULTS Youth with type 1 diabetes performed more poorly than controls on working memory ( p < .05 ) . Early onset diabetes was related to poorer sustained ( p < .001 ) and divided attention ( p = .001 ) , new learning , and mental efficiency ( both p < .05 ) . Hypoglycemia was found to adversely effect verbal abilities , working memory , and non-verbal processing speed ( all p < .05 ) . Poorer working memory was associated with hyperglycemia ( p < .05 ) . Youth with any combination of two or three illness risk factors ( i.e. , early onset diabetes , hypo- , hyperglycemia ) , performed more poorly than controls and youth with no or one risk on verbal abilities , working memory , and mental efficiency . CONCLUSIONS This study documents poorer neuropsychological performance and its association with illness risk factors in youth with type 1 diabetes . Findings suggest that early disease onset and hypoglycemia impact on the developing central nervous system , with hyperglycemia playing a lesser role Abstract . Aims /hypothesis : Good metabolic control in diabetic children is already crucial before puberty to prevent diabetic complications later in life . However , tight metabolic control could increase the risk of severe hypoglycaemia , which might be responsible for impaired intellectual performance later in life . The purpose of this prospect i ve longitudinal study was to evaluate the relevance of long-term metabolic control and hypoglycaemia possibly affecting the intellectual development of young children with Type I ( insulin-dependent ) diabetes mellitus . Methods : The intellectual development in 64 diabetic children between the ages of 7 and 16 years was assessed at least four times using the German version of the Hamburg Wechsler intelligence scale for preschool children , Children-Revised and by the “ Adaptives Intelligenz Diagnostikum ” ( Adaptive Intelligence Diagnosticum ) . Data were analysed longitudinally compared with a control group . Results : A significant decline in performance by age 7 and in verbal intelligence quotient between age 7 and 16 years was observed in diabetic boys diagnosed before the age of 6 but not in those diagnosed later and not in diabetic girls . The deterioration of intellectual performance in boys diagnosed at a very young age was not associated with the occurrence of severe hypoglycaemic episodes but was correlated with the degree of metabolic deterioration at diagnosis and with high long-term average of glycated haemoglobin . Conclusion /interpretation : Our study in diabetic children shows that the male sex , diagnosis at a young age , metabolic condition at diagnosis and long-term metabolic control , rather than experienced hypoglycaemic attacks are risk factors for intellectual development . [ Diabetologia ( 2002 ) 45 : 108–114 OBJECTIVE This study examined illness-related change in intelligence quotient ( IQ ) in a cohort of youth with type 1 diabetes studied prospect ively from disease onset in childhood to follow-up 12 years later in late adolescence/early adulthood . RESEARCH DESIGN AND METHODS Participants included type 1 diabetes patients ( n = 95 ; mean age at follow-up 21.3 years ) and healthy control participants ( HCs ; n = 67 ; mean age at follow-up 21.0 years ) from a cohort followed prospect ively . Measures included Wechsler Preschool and Primary Scale of Intelligence-Revised , Wechsler Intelligence Scale for Children-Revised , and Wechsler Abbreviated Scale of Intelligence and prospect i ve collection of data on metabolic control history . RESULTS Young people with type 1 diabetes showed greater decline in verbal IQ ( VIQ ) and full-scale IQ ( FSIQ ) , but not performance IQ ( PIQ ) , than HCs . Within the diabetes group , a younger age at diabetes onset was associated with a decline in PIQ and FSIQ ( P ≤ 0.001 ) . A history of hypoglycemic seizures was associated with a decline in VIQ ( P = 0.002 ) . Long-term metabolic control was not associated with changes in IQ . Interaction terms were not significant , suggesting no moderating effect of one diabetes-related variable over another . CONCLUSIONS The presence of diabetes may negatively influence some aspects of IQ over time . Specific illness risk factors , such as an earlier age of disease onset and a history of hypoglycemic seizures , appear to put the young person at greater risk . Academic progress of children identified as at risk should be monitored and educational supports provided if necessary OBJECTIVE Acute hypoglycemia in humans impairs cognitive functions and alters mood states . The time required for cognitive functions and moods to return to normal after an acute episode of severe hypoglycemia Output:	SH in early childhood-onset diabetes , especially seizures and coma , was associated with poorer memory ( verbal and visuospatial ) , as well as verbal intelligence . Among adult-onset diabetes , SH was associated with poorer cognitive performance in the older age ( > 55 years ) group only . Early versus late exposure to SH had a significant association with cognitive dysfunction ( CD ) . NSH and NH did not have any significant association with CD , while impaired awareness of hypoglycaemia was associated with poorer memory and cognitive-processing speeds . Conclusion The effect of SH on cognitive function is age dependent .
MS22117	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Effective clinical weight management approaches are needed to reach African-Americans . METHODS African-Americans recruited through outpatient practice s for a culturally-adapted Healthy Eating and Lifestyle Program were offered 10 weekly weight loss classes ( Phase 1 ) with the option of continuing for another 8 - 18 months ( Phase 2 ) in a r and omized comparison of further group counseling or staff-facilitated self-help vs. follow-up clinic visits only . RESULTS Of 237 enrollees ( 91 % women ; mean age 43.5 years ; mean body mass index 38.0 kg/m(2 ) ) , 70 [ corrected ] attended no classes or only the first Phase 1 class , 134 provided Phase 1 follow-up data , 128 were r and omized in Phase 2 , and 87 provided final follow-up data ( " completers " ) . Mean weight changes for completers were : -1.5 ( P < 0.001 ) , + 0.3 ( P = 0.47 ) , and -1.2 ( P = 0.04 ) kg , respectively , for Phase 1 , Phase 2 , and overall ( baseline to final visit ; average 18 months total duration ) , with no Phase 2 treatment effect ( P = 0.55 ) . Final study weight was > or = 5 % below baseline for 25 % of completers and was strongly predicted by Phase 1 weight loss . CONCLUSIONS Weight loss achieved in Phase 1 was maintained even with relatively minimal follow-up contact . Increasing the percent who achieve clinical ly significant weight loss initially would improve long-term results This article reports the results of two studies evaluating strategies to improve maintenance of weight loss . Study 1 evaluated the effect of frequent contact with patients through phone calls design ed to promote adherence to self-monitoring ; Study 2 evaluated a crisis intervention model , where subjects could obtain food boxes during high-risk periods to simplify dietary adherence . All subjects had originally participated in an initial six-month behavioral weight control program conducted at the University of Minnesota or at the University of Pittsburgh and had lost > 4.0 kg . Subjects from the University of Minnesota ( N=53 ) were r and omly assigned to either a year-long maintenance program involving weekly phone calls from a staff member or to a no-contact control ( Study 1 ) . Weekly phone calls , which inquired about self-monitoring and current weight , were completed with high frequency ( 76 % completion rate ) ; call completion and self-reported adherence to daily monitoring were negatively associated with weight regain ( r=−0.52 to −0.59 , p<.01 ) . However , weight regain did not differ significantly in the Phone Maintenance versus Control Condition ( + 3.9 kg versus + 5.6 kg , p=.28 ) . Study 2 , conducted at the University of Pittsburgh , involved 47 subjects who were r and omly assigned to a Control or Optional Food Provision Condition . Both groups attended monthly maintenance meetings ; the Food Provision Group had the option of purchasing boxes of food containing five breakfasts and five dinners . Twelve of the 26 subjects in the Food Provision Group purchased these food boxes for at least one month of maintenance . However , weight regain in those people who purchased the box , or in the Food Provision Condition as a whole , did not differ from the Control Condition ( + 4.2 kg for intervention versus + 4.3 kg for control ) . Further research is needed to develop more effective maintenance interventions OBJECTIVE The current study examined ethnic differences in patterns of weight loss and regain in response to an initial behavioral weight loss intervention followed by an extended-care maintenance program . METHODS We analyzed data from 224 women ( African American n = 43 , Caucasian n = 181 ) from rural communities who participated in an initial 6-month lifestyle intervention for obesity and were then r and omized to a face-to-face , telephone , or educational/control extended-care condition . RESULTS African American participants lost less weight during the initial phase of treatment than Caucasian participants ( mean + /- SE = -6.8 + /-.80 vs -10.7 + /- .38 kg , respectively , P = .003 ) . Investigating weight change during month 6 to month 18 , we found a significant interaction between ethnicity and the provision of an extended-care program . Caucasian participants r and omized to either of two extended-care programs regained less weight than those assigned to the control condition ( 1.2 + /- .58 and 4.2 + /- .79 kg , respectively , P=.003 ) , but the provision of extended care did not influence weight regain among African American participants ( 1.9 + /- 1.12 and 1.34 + /- 2.04 kg , respectively , P = .815 ) . CONCLUSION Collectively , these findings suggest that although African American participants lost less weight during the initial phase of treatment , they exhibited better long-term weight-loss maintenance than Caucasian participants . Further , while the provision of extended care successfully enhanced weight maintenance among Caucasian participants , African American participants maintained their initial weight losses regardless of extended care BACKGROUND Since many successful dieters regain the weight they lose , programs that teach maintenance skills are needed . We developed a maintenance program based on self-regulation theory and tested the efficacy of delivering the program face to face or over the Internet . METHODS We r and omly assigned 314 participants who had lost a mean of 19.3 kg of body weight in the previous 2 years to one of three groups : a control group , which received quarterly newsletters ( 105 participants ) , a group that received face-to-face intervention ( 105 ) , and a group that received Internet-based intervention ( 104 ) . The content of the programs in the two intervention groups was the same , emphasizing daily self-weighing and self-regulation , as was the frequency of contact with the groups . The primary outcome was weight gain over a period of 18 months . RESULTS The mean ( + /-SD ) weight gain was 2.5+/-6.7 kg in the face-to-face group , 4.7+/-8.6 kg in the Internet group , and 4.9+/-6.5 kg in the control group , with a significant difference between the face-to-face group and the control group ( 2.4 kg ; 95 % confidence interval [ CI ] , 0.002 to 10.8 ; P=0.05 ) . The proportion of participants who regained 2.3 kg or more over the 18-month period was significantly higher in the control group ( 72.4 % ) than in the face-to-face group ( 45.7 % ; absolute difference , 27 % ; 95 % CI , 14 to 39 ; P<0.001 ) or the Internet group ( 54.8 % ; absolute difference , 18 % ; 95 % CI , 5 to 30 ; P=0.008 ) . Daily self-weighing increased in both intervention groups and was associated with a decreased risk of regaining 2.3 kg or more ( P<0.001 ) . CONCLUSIONS As compared with receiving quarterly newsletters , a self-regulation program based on daily weighing improved maintenance of weight loss , particularly when delivered face to face . ( Clinical Trials.gov number , NCT00067145 [ Clinical Trials.gov ] . The present study compared the relative effectiveness of a therapist-supported maintenance condition with a minimal contact maintenance condition in preventing relapse following an obesity treatment program . Thirty-two subjects who completed an initial 12-week cognitive/behavioral plus aerobic exercise treatment program were matched on absolute weight loss and r and omly assigned to one of two maintenance conditions . Subjects were assessed at pretreatment , posttreatment , and 3 , 6 , and 12 months following posttreatment using measures of weight , blood pressure , and depression . Three- and six-month follow-up results indicated that subjects who participated in the therapist-supported maintenance group continued to lose weight and /or maintained therapy-induced weight loss to a greater degree than control subjects . At the 12-month follow-up assessment therapist-supported subjects maintained therapy-induced weight loss better than the control subjects . These findings suggest that maintenance programs which provide continued contact emphasizing relapse prevention training may be an important adjunct in the maintenance of therapy-induced weight loss OBJECTIVE —The effectiveness of intentional weight loss in reducing cardiovascular disease ( CVD ) events in type 2 diabetes is unknown . This report describes 1-year changes in CVD risk factors in a trial design ed to examine the long-term effects of an intensive lifestyle intervention on the incidence of major CVD events . RESEARCH DESIGN AND METHODS —This study consisted of a multicentered , r and omized , controlled trial of 5,145 individuals with type 2 diabetes , aged 45–74 years , with BMI > 25 kg/m2 ( > 27 kg/m2 if taking insulin ) . An intensive lifestyle intervention ( ILI ) involving group and individual meetings to achieve and maintain weight loss through decreased caloric intake and increased physical activity was compared with a diabetes support and education ( DSE ) condition . RESULTS — Participants assigned to ILI lost an average 8.6 % of their initial weight vs. 0.7 % in DSE group ( P < 0.001 ) . Mean fitness increased in ILI by 20.9 vs. 5.8 % in DSE ( P < 0.001 ) . A greater proportion of ILI participants had reductions in diabetes , hypertension , and lipid-lowering medicines . Mean A1C dropped from 7.3 to 6.6 % in ILI ( P < 0.001 ) vs. from 7.3 to 7.2 % in DSE . Systolic and diastolic pressure , triglycerides , HDL cholesterol , and urine albumin-to-creatinine ratio improved significantly more in ILI than DSE participants ( all P < 0.01 ) . CONCLUSIONS —At 1 year , ILI result ed in clinical ly significant weight loss in people with type 2 diabetes . This was associated with improved diabetes control and CVD risk factors and reduced medicine use in ILI versus DSE . Continued intervention and follow-up will determine whether these changes are maintained and will reduce CVD risk This study compared 2 extended therapy programs for weight management with st and ard behavioral treatment ( BT ) without additional therapy contacts . Participants were 80 obese women who completed 20 weekly group sessions of BT and achieved a mean initial weight loss of 8.74 kg . Participants were r and omly assigned to a no-further-contact condition ( BT only ) or to one of two extended interventions consisting of relapse prevention training ( RPT ) or problem-solving therapy ( PST ) . No significant overall weight-change differences were observed between RPT and BT or between RPT and PST . However , participants who completed the PST intervention had significantly greater long-term weight reductions than BT participants , and a significantly larger percentage of PST participants achieved clinical ly significant losses of 10 % or more in body weight than did BT participants ( 35 % vs. 6 % ) OBJECTIVE This study assessed whether a 5 % to 10 % reduction in initial weight would be associated with as favorable long-term ( i.e. , 100 weeks ) changes in lipids and lipoproteins , as have been observed on a short-term basis ( i.e. , 8 weeks ) . RESEARCH METHODS AND PROCEDURES This was a prospect i ve evaluation of 25 obese women , each of whom had lost > or = 5 % of initial weight during 48 weeks of treatment and had maintained a weight loss of this magnitude at 1-year follow-up ( week 100 ) . Lipids and lipoproteins were obtained at baseline and at weeks 8 , 24 , 48 , and 100 . All participants had a baseline total cholesterol > or = 5.17 mmol/L ( 200 mg/dL ) . RESULTS At the end of the first 8 weeks , weight fell an average of 11.7+/-2.8 % , total cholesterol 20.6+/-7.5 % , low-density-lipoprotein ( LDL ) cholesterol 23.0+/-18.1 % , and triglycerides 26.0+/-20.1 % . At week 48 , weight had fallen to 20.1+/-7.0 % below baseline , but total cholesterol and LDL cholesterol were reduced only 11.5+/-10.4 % and 12.0+/-14.0 % below baseline , respectively . These latter reductions were significantly ( p<0.05 ) smaller than those observed at week 8 , despite the larger weight loss at week 48 . High-density-lipoprotein cholesterol declined significantly ( p<0.05 ) during the first 8 weeks , but returned to baseline values by week 24 . Patients gained 7.4+/-7.4 kg from weeks 48 to 100 , during which time total and LDL cholesterol ( but not triglycerides ) rose significantly ( p<0.05 ) . Patients who , at week 100 , maintained losses > 10 % of initial weight had significantly greater reductions in total and LDL cholesterol values than did patients who maintained losses of only 5 % to 10 % of initial weight . DISCUSSION Results of this study underscore the importance of assessing long-term changes in weight-related health complications when patients have lost weight but are no longer dieting ( and exercising ) as aggressively as they did during the initial months of treatment OBJECTIVE To investigate the efficacy of an Internet weight maintenance program . RESEARCH METHODS AND PROCEDURES Two hundred fifty-five healthy overweight and obese adults ( mean + /- SD BMI , 31.8 + /- 4.1 kg/m(2 ) ) men ( 18 % ; mean + /- SD age , 4 Output:	These findings suggest that extended care is a viable and efficacious solution to addressing long-term maintenance of lost weight .
MS22118	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Rationale Serotonin is shown to regulate the activity of primary auditory cortex , but little is known about serotonin modulation of other sensory cortices . Methods We investigated somatosensory evoked magnetic fields ( SEF ) to left median nerve stimulation in eight healthy subjects in a double-blind , controlled , cross-over design study after acute tryptophan depletion ( ATD ) and control mixture . SEFs were recorded with the whole-head magnetoencephalography 6 h after ingestion of mixtures . The SEF sources and strength were estimated by a least-squares fit of a single equivalent current dipole . Results ATD decreased the total and free TPR levels by 75 and 48 % and control mixture increased them by 98 % and 44 % . ATD had no effect on the amplitudes or latencies of SEF components . The source locations of the responses were not significantly affected by ATD . ConclusionS erotonin does not affect stimuli processing in the primary somatosensory cortex Abstract Serotonin ( 5-hydroxytryptamine ; 5-HT ) circuits may play a role in cognitive performance , particularly in learning and memory . Cognitive impairment is often seen in depressed patients , in whom 5-HT turnover in the brain is thought to be lowered . A possible human pharmacological model to study the involvement of the serotonergic system in cognitive impairment is to reduce central 5-HT synthesis through L-tryptophan depletion in healthy subjects . In this study , the cognitive effects of tryptophan depletion were assessed and whether genetically or developmentally determined vulnerability factors were predictive of the cognitive impairment induced by tryptophan depletion . Sixteen healthy volunteers with a positive family history of depression and 11 without were given 100 g of an amino acid mixture with or without tryptophan , according to a double-blind , cross-over design . Tryptophan depletion specifically impaired long-term memory performance in all subjects : delayed recall performance , recognition sensitivity , and recognition reaction times were significantly impaired after tryptophan depletion relative to placebo . Short-term memory and perceptual and psychomotor functions were unchanged . There were no differences between groups with a positive and a negative family history for depression . On the basis of these results , it is concluded that tryptophan depletion specifically impairs long-term memory formation , presumably as a result of an acute decrease in 5-HT turnover in the brain Rationale and objective In animal and human studies , the neurotransmitter serotonin ( 5-hydroxytryptamine ; 5-HT ) has been implicated in mediating impulsiveness and aggression . To test the hypothesis that 5-HT modulates neuro-cognitive brain activation during inhibitory control , we examined the effect of acute tryptophan depletion ( ATD ) , a dietary challenge , which has been shown to decrease 5-HT synthesis in the brain , on functional brain activation during a go/no-go task . Methods Nine healthy , right-h and ed volunteers performed a rapid , event-related go/no-go task in two functional magnetic resonance imaging ( fMRI ) scanning sessions , 5 h after either a tryptophan-free or a balanced amino acid drink in a double-blind , sham depletion-controlled , counterbalanced , crossover design . The task required subjects to selectively execute or inhibit a motor response . Tryptophan depletion significantly lowered total plasma tryptophan concentration by 80 % , but did not significantly alter inhibitory performance or mood ratings . Results ATD significantly reduced right orbito-inferior prefrontal activation during the no-go condition , and increased activation in superior and medial temporal cortices . Conclusions These findings provide neuro-functional evidence of a serotonergic modulation of right inferior prefrontal during inhibitory motor control . The increased engagement of temporal brain regions may reflect compensatory mechanisms BACKGROUND The amygdala has a central role in processing emotions , particularly fear . During functional magnetic resonance imaging ( fMRI ) amygdala activation has been demonstrated outside of conscious awareness using masked emotional faces . METHODS We applied the masked faces paradigm to patients with major depression ( n = 11 ) and matched control subjects ( n = 11 ) during fMRI to compare amygdala activation in response to masked emotional faces before and after antidepressant treatment . Data were analyzed using left and right amygdala a priori regions of interest , in an analysis of variance block analysis and r and om effects model . RESULTS Depressed patients had exaggerated left amygdala activation to all faces , greater for fearful faces . Right amygdala did not differ from control subjects . Following treatment , patients had bilateral reduced amygdala activation to masked fearful faces and bilateral reduced amygdala activation to all faces . Control subjects had no differences between the two scanning sessions . CONCLUSIONS Depressed patients have left amygdala hyperarousal , even when processing stimuli outside conscious awareness . Increased amygdala activation normalizes with antidepressant treatment Involuntary attention shifting , i.e. , detecting and orienting to unexpected stimulus changes , may be altered at low brain serotonin ( 5-hydroxytryptamine ; 5-HT ) levels . This was studied in 13 healthy subjects ( 21 - 30 years old ; 6 females ) by using a dietary challenge , acute tryptophan depletion ( ATD ) , which decreases 5-HT synthesis in the brain . Five hours after ingestion of either ATD or control mixture ( r and omized , double-blinded , crossover design ) , brain responses indexing involuntary attention were measured with simultaneous 64-channel electroencephalography ( EEG ) and 122-channel magnetoencephalography ( MEG ) . During the measurement , the subjects were instructed to discriminate equiprobable 200- and 400-ms tones by pressing one of two buttons rapidly . Occasionally , the frequency of the tones changed ( 10 % increase/decrease ) , causing involuntary attention shifting . ATD significantly lowered plasma tryptophan concentrations ( total tryptophan decreased by 75 % , free tryptophan decreased by 35 % ) . As compared to the control condition , ATD reduced the amplitude of the deviant-tone N2 wave , including the overlapping mismatch negativity ( MMN ) and N2b subcomponents , which are suggested to reflect change detection in the brain . The EEG results were accompanied by a significant increase in the peak latency of the magnetic counterpart of MMN . However , no ATD effects were observed in P3 to task-irrelevant frequency change . Reaction time ( RT ) to deviants per se was not significantly affected , but RT in trials succeeding the deviant-frequency tones was increased by ATD , which suggested impaired reorienting to the task-relevant activity . In conclusion , the results suggest that decreased level of central 5-HT function after ATD may decrease involuntary attention shifting to task-irrelevant sound changes and thus modulate re source allocation to the task-relevant activity To eluci date serotonin modulation of selective attention , 13 volunteers ( 21 - 30 years ) were studied in two sessions , 5 h after either acute tryptophan depletion ( ATD ) that decreases brain serotonin synthesis , or control-mixture ingestion ( r and omized , double-blind , cross-over design ) . Simultaneous electroencephalogram and magnetoencephalogram were measured during dichotic listening of two concurrent trains of st and ard and deviant tones . Subjects counted the deviants presented to one ear and ignored those presented to the other ear . ATD lowered plasma total tryptophan by 75 % and free tryptophan by 39 % . ATD suppressed the amplitude enhancement of P50 and N1 to selectively attended tones , but did not affect the later aspects of processing negativity . The P50 latencies were increased after ATD , irrespective of attention . In conclusion , serotonin may regulate attentional modulation of early cortical stimulus processing Several lines of evidence suggest that the auditory evoked potential ( AEP ) augmenting/reducing slope may serve as a biological marker of central serotonergic activity . According to Hegerl and Juckel ( Biol . Psychiatry , 33 , 1993 , 173 ) , reduced serotonergic activity is hypothesized to increase the slope of the AEP amplitude stimulus intensity function ( ASF-slope ) . Hints for this hypothesis were investigated by employing the acute tryptophan depletion paradigm in 18 healthy females . A within-subject , placebo controlled double-blind cross over design was used for that purpose . Subjects ingested both a 50 g amino-acid drink with ( placebo condition ) and without tryptophan ( depletion condition ) . With respect to the N1/P2-slope , test-retest reliability of a 1 week interval ranged between r=0.56 and 0.58 for the pre-ingestion baseline recording sessions . Affect was not altered by tryptophan depletion and not related to the ASF-slope . The comparison between placebo and depletion conditions did not reveal significant alterations of the ASF-slope , neither after 5 nor 6 h post-ingestion . Thus , the results do not support the assumption of the ASF-slope reflecting central serotonergic function Abstract Rationale . Intensity dependence of the N1/P2 components may be regulated by serotonergic neurons in the primary auditory cortex , where low activity leads to a high intensity dependence and vice versa . Depletion of tryptophan ( TRP ) , a precursor for serotonin has been described to reduce serotonin content in brain of animals and humans . Objective . We investigated the intensity dependence of magnetic and electric N1/P2 components in ten subjects in a double-blind , controlled , cross-over design study after oral mixture of amino-acids leading to acute tryptophan depletion ( ATD ) and control . Methods . Auditory evoked magnetic fields ( AEF ) and potentials ( AEP ) were recorded with 122-channel magnetoencephalography simultaneously with 64-channel EEG 5 h after ingestion of mixtures . The AEF sources and strength were estimated by a least-squares fit of a single equivalent current dipole . The amplitudes and latencies of N1 and P2 recorded with EEG were analyzed at frontal electrode site . Results . TRP depletion decreased the total and free TRP levels by 76 and 45 % and control mixture increased it by 48 and 28 % . ANOVA showed that ATD had a significant main effect on the N1m/P2 m dipole moments at the contralateral ( P=0.02 ) , but failed significantly to influence the ipsilateral responses . A significant mixture ingestion-by-stimulus intensity interaction was observed on the N1m/P2 m dipole moments at the contralateral hemisphere ( P=0.01 ) . The N1/P2 slope for intensity dependence function was decreased following ATD compared with the control experiment ( P=0.01 ) at the contralateral hemisphere . For EEG , a significant mixture ingestion-by-stimulus intensity interaction on the N1 latencies at the Fz electrode position was observed ( P=0.01 ) . Conclusion . ATD decreased the intensity dependence of N1m/P2 m source dipole moments in the primary auditory cortex at the hemisphere contralateral to the ear stimulated . These results suggest that serotonin participates in the regulation of intensity of auditory stimulation We studied the effects of acute tryptophan depletion ( ATD ) on early cortical auditory processing . Middle-latency auditory evoked fields ( MAEF ) were investigated in 14 healthy subjects after 5 h of ATD or control mixture ingestion in a r and omized , double-blinded , controlled cross-over design study . MAEFs to monaural click stimuli ( 0.1-ms duration ) were recorded with a 122-channel neuromagnetometer . Total plasma tryptophan ( Trp ) , free Trp , and large neutral amino acid ( LNAA ) concentrations were determined by using high-performance liquid chromatography . ATD lowered the total plasma Trp levels by 75 % , free Trp level by 47 % , and the ratio Trp/ΣLNAA by 92 % . The control mixture increased total Trp level by 45 % and free Trp by 32 % , and decreased the ratio Trp/ΣLNAA by 35 % . The ratio tyrosine/ΣLNAA did not differ between ATD and control experiment . ATD result ed in a significant main effect on Pam latencies and a near-significant main effect on Pam amplitudes . A significant Mixture ingestion X Sex interaction on Nbm amplitude and a significant Mixture ingestion X Sex X Hemisphere interaction on Pam latency were observed . ATD did not affect the MAEF source dipoles . The Pam latencies in both hemispheres had a significant negative relationship with the extent of ATD . The results suggest that the neurotransmitter serotonin is involved in early auditory cortical processing . Further , the serotonin modulation may be different in males and females Event-related functional magnetic resonance imaging was used to measure blood oxygenation level-dependent responses in 13 young healthy human volunteers during performance of a probabilistic reversal-learning task . The task allowed the separate investigation of the relearning of stimulus – reward associations and the reception of negative feedback . Significant signal change in the right ventrolateral prefrontal cortex was demonstrated on trials when subjects stopped responding to the previously relevant stimulus and shifted responding to the newly relevant stimulus . Significant signal change in the region of the ventral striatum was also observed on such reversal errors , from a region of interest analysis . The ventrolateral prefrontal cortex and ventral striatum were not significantly activated by the other , preceding reversal errors , or when subjects received negative feedback for correct responses . Moreover , the response on the final reversal error , before shifting , was not modulated by the number of preceding reversal errors , indicating that error-related activity does not simply accumulate in this network . The signal change in this ventral fr Output:	Although tryptophan depletion reduced plasma serotonin levels in all studies , significant effects on mood were only observed in studies with recovered depressed patients . In functional neuroimaging studies ATD was consistently found to modulate cortical activity in prefrontal areas implicated in mnemonic and executive functions and in orbitofrontal , cingulate , and subcortical regions associated with emotional processing . Electrophysiological studies indicated that ATD has a significant effect on both “ selective ” and “ involuntary ” attention . Conclusions The combination of ATD with modern brain imaging techniques allows the investigation of the neurophysiological effects of reduced 5-HT synthesis on global brain activity , executive functions , memory , attention , and affect
MS22119	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The Life Education organization offers a drug education programme to an estimated one million Australian primary schoolchildren . It is believed the programme delays experimentation with or initiation into smoking , alcohol use and the taking of analgesics . This study examined the short-term public health effects on 3000 11- and 12-year-old students , of whom 1700 were exposed to 5 consecutive years of the programme . The other 1300 students were not exposed to the programme . After controlling for the known predictors of social drug use there was no evidence that Life Education students , when compared with students receiving conventional school-based drug education , were less likely to have smoked , were less likely to have drunk or were less likely to have used analgesics . Indeed , the evidence suggested that Life Education-students were slightly more likely to use these substances , and that the programme had different effects on boys ' and girls ' drug use . Given that these findings are consistent with previous research evaluating similar drug education programmes , it is hypothesized they are most likely to do with the design of the programme itself Objective : The aim of the present study was to conduct a cross-validation trial of the efficacy of a computerized school-based intervention for alcohol misuse in adolescents . Method : A cluster r and omized control trial was carried out . Intervention and control groups were assessed at baseline , immediately after and 6 months after the intervention . A total of 764 Year 8 students from 10 independent secondary schools in Sydney , Australia participated in the study . Half of the schools were r and omly allocated to the computerized prevention programme ( n=397 ) , and half to their usual classes ( n=367 ) . The six-lesson computerized intervention was evidence and curriculum based while having a focus on harm-minimization . Knowledge , expectancies , alcohol consumption ( frequency , quantity and binging ) , patterns of use , and harms associated with one 's own use of alcohol were assessed . Results : There were significant improvements in knowledge regarding alcohol use at immediate and 6 month follow up . Average weekly alcohol consumption was reduced immediately after the intervention . No differences between groups were found on alcohol expectancies , frequency of drinking to excess and harms related to alcohol use over time . Conclusions : The present results support the Climate Management and Treatment Education ( CLIMATE ) Schools : alcohol module as an effective intervention in increasing alcohol knowledge and reducing alcohol use in the short term AIMS The School Health and Alcohol Harm Reduction Project ( SHAHRP study ) aim ed to reduce alcohol-related harm in secondary school students . DESIGN The study used a quasi-experimental research design in which r and omly selected and allocated intervention and comparison groups were assessed at eight , 20 and 32 months after baseline . SETTING Metropolitan , government secondary schools in Perth , Western Australia . PARTICIPANTS The sample involved over 2300 students . The retention rate was 75.9 % over 32 months . INTERVENTION The evidence -based intervention , a curriculum programme with an explicit harm minimization goal , was conducted in two phases over a 2-year period . MEASURES Knowledge , attitude , total alcohol consumption , risky consumption , context of use , harm associated with own use and harm associated with other people 's use of alcohol . FINDINGS There were significant knowledge , attitude and behavioural effects early in the study , some of which were maintained for the duration of the study . The intervention group had significantly greater knowledge during the programme phases , and significantly safer alcohol-related attitudes to final follow-up , but both scores were converging by 32 months . Intervention students were significantly more likely to be non-drinkers or supervised drinkers than were comparison students . During the first and second programme phases , intervention students consumed 31.4 % and 31.7 % less alcohol . Differences were converging 17 months after programme delivery . Intervention students were 25.7 % , 33.8 % and 4.2 % less likely to drink to risky levels from first follow-up onwards . The intervention reduced the harm that young people reported associated with their own use of alcohol , with intervention students experiencing 32.7 % , 16.7 % and 22.9 % less harm from first follow-up onwards . There was no impact on the harm that students reported from other people 's use of alcohol . CONCLUSIONS The results of this study support the use of harm reduction goals and classroom approaches in school drug education AIMS To determine the impact of a school-based harm minimization smoking intervention compared to traditional abstinence-based approaches . DESIGN , SETTING AND PARTICIPANTS A school-based cluster r and omized trial was conducted in Perth , Western Australia in 30 government high schools from 1999 to 2000 . Over 4000 students were recruited to participate and schools were assigned r and omly to either the harm minimization intervention or a st and ard abstinence-based programme . INTERVENTION The harm minimization intervention comprised eight 1-hour lessons over 2 years , quitting support from school nurses and enactment of policies to support programme components . Comparison schools implemented st and ard abstinence-based programmes and policies . MEASURES Cigarette smoking was categorized at two levels : regular smoking , defined as smoking on 4 or more days in the previous week ; and 30-day smoking as any smoking within the previous month . FINDINGS At immediate post-test ( 20 months post-baseline ) , after accounting for baseline differences , school-level clustering effects , socio-economic status , gender and family smoking , intervention students were less likely to smoke regularly [ OR = 0.51 , 95 % confidence interval ( CI ) = 0.36 , 0.71 ] or to have smoked within the previous 30 days ( OR = 0.69 , 95 % CI = 0.53 , 0.91 ) . CONCLUSION The school-based adolescent harm minimization intervention appears to have been more effective than the abstinence-based social influences programme at reducing regular smoking CONTEXT Selective interventions targeting personality risk are showing promise in the prevention of problematic drinking behavior , but their effect on illicit drug use has yet to be evaluated . OBJECTIVE To investigate the efficacy of targeted coping skills interventions on illicit drug use in adolescents with personality risk factors for substance misuse . DESIGN R and omized controlled trial . SETTING Secondary schools in London , United Kingdom . PARTICIPANTS A total of 5302 students were screened to identify 2028 students aged 13 to 16 years with elevated scores on self-report measures of hopelessness , anxiety sensitivity , impulsivity , and sensation seeking . Seven hundred thirty-two students provided parental consent to participate in this trial . INTERVENTION Participants were r and omly assigned to a control no-intervention condition or a 2-session group coping skills intervention targeting 1 of 4 personality profiles . MAIN OUTCOME MEASURES The trial was design ed and powered to primarily evaluate the effect of the intervention on the onset , prevalence , and frequency of illicit drug use over a 2-year period . RESULTS Intent-to-treat repeated- measures analyses on continuous measures of drug use revealed time x intervention effects on the number of drugs used ( P < .01 ) and drug use frequency ( P < .05 ) , whereby the control group showed significant growth in the number of drugs used as well as more frequent drug use over the 2-year period relative to the intervention group . Survival analysis using logistic regression revealed that the intervention was associated with reduced odds of taking up the use of marijuana ( beta = -0.3 ; robust SE = 0.2 ; P = .09 ; odds ratio = 0.7 ; 95 % confidence interval , 0.5 - 1.0 ) , cocaine ( beta = -1.4 ; robust SE = 0.4 ; P < .001 ; odds ratio = 0.2 ; 95 % confidence interval , 0.1 - 0.5 ) , and other drugs ( beta = -0.7 ; robust SE = 0.3 ; P = .03 ; odds ratio = 0.5 ; 95 % confidence interval , 0.3 - 0.9 ) over the 24-month period . CONCLUSION This study extends the evidence that brief , personality-targeted interventions can prevent the onset and escalation of substance misuse in high-risk adolescents . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00344474 This study examined the impact of a school-based preventive intervention on cannabis use in adolescence , using a cluster-r and omized trial of a multilevel intervention aim ed at improving social relationships within schools by promoting change in school environment . Four waves of data were collected at baseline ( 1997 , Year 8 : mean age 13 years ) and six , 18 , and 30 months later ( 1999 , Year 10 : mean age 16 years ) . Self-reported substance use , school engagement , and sociodemographic data were collected using computer-administered question naires . Some 2.678(74 % ) Year 8 students participated ( wave 1 ) with minimal attrition ( 10 % by wave 4 ) . Adjusting for baseline use , weak evidence existed for an intervention effect on the prevalence of any use at Year 10 ( OR 0.75 , 95 % CI 0.54 , 1.05 ) and incident weekly use ( OR 0.72 , 95 % CI 0.39 , 1.33 ) . These effects were reduced after adjusting for confounders . Moderate evidence suggested an interaction effect between intervention group and tobacco use ( p = 0.04 ) , suggesting the intervention was more effective for non-smokers at baseline ( Adj . OR 0.50 , 95 % CI 0.26 , 0.98 ) . This study indicates that a multi-level school-based program may provide an innovative direction for sustainable school interventions with the potential to reduce substance use INTRODUCTION AND AIMS This study aim ed to examine : ( a ) the influence of family factors relative to school , peer and individual influences on the development of adolescent alcohol use during the first year of secondary school ; and ( b ) the feasibility of preventing adolescent alcohol use by modifying family factors . DESIGN AND METHODS Twenty-four schools in Melbourne , Australia were r and omly assigned to either the ' Resilient Families ' intervention or a control condition . A baseline cohort of 2315 grade 7 students ( mean age 12.3 years ) were followed-up one year later ( n=2128 for longitudinal analyses ) . A sub-set of parents ( n=1166 ) also returned baseline surveys . RESULTS The prevalence of lifetime alcohol use in year 7 was 33 % and rose to 47 % by year 8 . Student-reported predictors of year 8 alcohol use included baseline alcohol [ Odds Ratio ( OR ) 3.64 ] and tobacco use ( 2.68 ) , and school friend 's alcohol ( 1.41 ) and tobacco use ( 1.64 ) . After adjusting for other influences , student-reported family factors were not maintained as significant predictors of year 8 alcohol use . Parent-report predictors of student-reported alcohol use included allowing alcohol use in the home ( 2.55 ) , parental alcohol use ( 1.88 ) and child hyperactivity ( 1.85 ) . Protective factors included attendance at brief parent education ( 0.60 ) and parent involvement in school education ( 0.65 ) . DISCUSSION AND CONCLUSIONS The intervention appeared to benefit education-related outcomes , but no overall effect in reducing student alcohol use was found in year 8 . Intervention effects on alcohol misuse may become significant in later secondary school once the entire program has been implemented . Considerable alcohol use was detected in early secondary school , suggesting that interventions to reduce alcohol use may be usefully implemented prior to this period AIMS Hazardous alcohol use is a leading cause of death among adolescents and young adults world-wide , yet few effective prevention interventions exist . This study was the first to examine a computerized harm minimization intervention to reduce alcohol misuse and related harms in adolescents . DESIGN Cluster r and omized controlled trial of a six-session curriculum-integrated harm minimization prevention program . The intervention was delivered by computer in the form of a teenage drama , which provided education through alcohol-related scenarios to which young people could relate . SETTING Schools in Australia . PARTICIPANTS A total of 1466 year 8 students ( 13 years ) from 16 high schools in Australia were allocated r and omly to a computerized prevention program ( n = 611 , eight schools ) or usual classes ( n = 855 , eight schools ) . MEASUREMENTS Change in knowledge , alcohol use , alcohol-related harms and alcohol expectancies . FINDINGS A computerized prevention program was more effective than usual classes in increasing alcohol-related knowledge of facts that would inform safer drinking choices and decreasing the positive social expectations which students believed alcohol may afford . For females it was effective in decreasing average alcohol consumption , alcohol-related harms and the frequency of drinking to excess ( more than four st and ard drinks ; 10 g ethanol ) . For males the behavioural effects were not significant . CONCLUSIONS A harm minimization approach is effective in educating young people about alcohol-related risks and is effective in reducing risky drinking and harms among girls . Reduction of problems among boys remains a challenge Objective . The purpose of this study was to compare the effects of a single drug , i.e. , alcohol , against a multiple drug preventive intervention . Methods . A controlled trial was conducted with 448 8th grade students ( mean age = 13 years old ) from an inner-city middle school ( n = 216 ) and a rural junior high school ( n = 232 ) in 2000–2001 . Students were r and omized within school , and 3-month post-intervention follow-up data were collected . Results . Output:	Existing school-based prevention programs have shown to be efficacious in the Australian context . The findings challenge the commonly held view that school-based prevention programs are not effective
MS22120	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Abstract Objective : To evaluate the effectiveness of combinations of three methods to promote physical activity . Design : R and omised controlled trial . Baseline assessment with post-intervention follow up at 12 weeks and 1 year . Setting : One urban general practice , 1995 - 7 . Participants : 523 adults aged 40 to 64 years , r and omised to four intervention groups and a control group . Interventions : Brief ( one interview ) or intensive ( six interviews over 12 weeks ) motivational interviewing based on the stages of change model of behaviour change , with or without financial incentive ( 30 vouchers entitling free access to leisure facilities ) . Main outcome measures : Physical activity score ; sessions of moderate and vigorous activity in the preceding four weeks . Results : Response rate was 81 % at 12 weeks and 85 % at one year . More participants in the intervention group reported increased physical activity scores at 12 weeks than controls ( 38 % v 16 % , difference 22 % , 95 % confidence interval for difference 13 % to 32 % ) , with a 55 % increase observed in those offered six interviews plus vouchers . Vigorous activity increased in 29 % of intervention participants and 11 % of controls ( difference 18 % , 10 % to 26 % ) , but differences between the intervention groups were not significant . Short term increases in activity were not sustained , regardless of intensity of intervention . Conclusions : The most effective intervention for promoting adoption of exercise was the most intensive . Even this did not promote long term adherence to exercise . Brief interventions promoting physical activity that are used by many schemes in the United Kingdom are of question able effectiveness . Key messages Schemes promoting physical activity are currently popular in general practice in Britain , but few have been rigorously evaluated and their effectiveness is unknown . In this study , the most effective intervention for promoting adoption of physical activity was the most intensive , involving six motivational interviews and a financial incentive A comparatively brief intervention ( one interview ) was only effective in the short term in around a third of participants Short term increases in physical activity were not maintained at one year follow up and even the most intensive intervention was ineffective in promoting long term adherence to increased physical activity . National and local government , health authorities , and primary healthcare teams should be cautious about current and future expenditure on , and implementation of , exercise prescription or referral BACKGROUND Using peer volunteers as delivery agents may improve translation of evidence -based physical activity promotion programs for older adults . This study examined whether tailored support from older peer volunteers could improve initiation and long-term maintenance of physical activity behavior . METHODS Participants were r and omized to 2 16-week , group-based programs : ( 1 ) peer-delivered , theory-based support for physical activity behavior change ; or ( 2 ) an intervention typically available in community setting s ( basic education , gym membership , and pedometer for self-monitoring ) , attention-matched with health education . Moderate-to-vigorous physical activity ( MVPA ) was assessed via daily self-report logs at baseline , at the end of the intervention ( 16 weeks ) , and at follow-up ( 18 months ) , with accelerometry validation ( RT3 ) in a r and om sub sample . RESULTS Seven peer volunteers and 81 sedentary adults were recruited . Retention at the end of the trial was 85 % and follow-up at 18 months was 61 % . Using intent-to-treat analyses , at 16 weeks , both groups had similar significant improvements in MVPA . At 18 months , the group supplemented with peer support had significantly more MVPA . CONCLUSIONS Trained peer volunteers may enhance long-term maintenance of physical activity gains from a community-based intervention . This approach has great potential to be adapted and delivered inexpensively in community setting Background Following an extensive recruitment campaign , a 16-week lunchtime intervention to increase walking was implemented with insufficiently physically active University employees to examine programme feasibility and the effects of the programme in increasing walking behaviour , and in improving well-being and work performance . Methods / design A feasibility study in which participants were r and omised to an immediate treatment or a delayed treatment control ( to start at 10 weeks ) group . For the first ten weeks of the intervention , participants took part in three facilitator-led group walks per week each of thirty minutes duration and were challenged to accumulate another sixty minutes of walking during the weekends . In the second phase of the intervention , the organised group walks ceased to be offered and participants were encouraged to self-organise their walks . Motivational principles were employed using contemporary motivational theory . Outcome measures ( including self-reported walking , step counts , cardiovascular fitness , general and work-related well-being and work performance ) were assessed at baseline , at the end of the 16-week intervention and ( for some ) four months after the end of the intervention . Process and outcome assessment s were also taken throughout , and following , the intervention . Discussion The results of the intervention will determine the feasibility of implementing a lunchtime walking programme to increase walking behaviour , well-being and performance in sedentary employees . If successful , there is scope to implement definitive trials across a range of worksites with the aim of improving both employee and organisational health . Trial registration Current Controlled Trials IS RCT N81504663 Mediation analyses in faith-based physical activity ( PA ) interventions targeting African-American adults are lacking . The purpose of this study was to examine the psychosocial mediators of a faith-based PA intervention with African-American adults . Churches were r and omly assigned to receive immediate or delayed ( 1-year later ) training in PA program implementation . A sub sample of participants from r and omly selected churches took part in telephone surveys at baseline and at 1 year . The primary outcome was percentage of participants meeting PA recommendations . MacKinnon 's product of coefficients was used to test for mediation . Participants ( n = 418 ) from 20 churches completed the baseline and 1-year follow-up surveys . There were no statistically significant changes in PA behavior at 1 year . The intervention had a marginally significant effect on increasing the amount of instrumental church support received by church members . However , none of the psychosocial variables tested were found to be significant mediators of the intervention . Mediation analyses provided insight into potential reasons as to why the Health-e-AME intervention did not change PA . The intervention did not successfully change the targeted mediators hypothesized to change PA . Potential reasons for these shortcomings as well as issues to address in future faith-based studies are discussed This paper reports on the cost-effectiveness of pedometer-based versus time-based Green Prescriptions in improving physical activity and health-related quality of life ( EQ-5D ) in a r and omised controlled trial of 330 low-active , community-based adults aged 65 years and over . Costs , measured in $ NZ ( NZ$1=A$0.83 , December 2008 ) , comprised public and private health care costs plus exercise-related personal expenditure . Based on intention-to-treat data at 12-month follow up , the pedometer group showed a greater increase in weekly leisure walking ( 50.6 versus 28.1min for the time-based group , adjusted means , P=0.03 ) . There were no significant between-group differences in costs . The incremental cost-effectiveness ratios , for the pedometer-based versus time-based Green Prescription , per 30min of weekly leisure walking and per quality -adjusted life year were , ( i ) when including only community care costs , $ 115 and $ 3105 , ( ii ) when including only exercise and community care costs , $ 130 and $ 3500 , and ( iii ) for all costs , -$185 and -$4999 , respectively . The cost-effectiveness acceptability curves showed that the pedometer-based compared with the time-based Green Prescription was statistically cost-effective , for the above cost categories , at the following quality -adjusted life year thresholds : ( i ) $ 30000 ; ( ii ) $ 30500 ; and ( iii ) $ 16500 . The additional program cost of converting one sedentary adult to an active state over a 12-month period was $ 667 . The outcomes suggest the pedometer-based Green Prescription may be cost-effective in increasing physical activity and health-related quality of life over 12 months in previously low-active older adults BACKGROUND Physical activity promotion is a priority , but contribution of physicians ' interventions is unclear . The effectiveness of the PEPAF ( " Experimental Program for Physical Activity Promotion " ) , which was implemented exclusively by physicians in routine primary care from October 2003 to December 2004 , was assessed . METHODS Fifty-six Spanish family physicians were r and omized to either the intervention ( n = 29 ) or st and ard care ( n = 27 ) arm of the trial . The physicians recruited 4317 physically inactive patients ( 2248 for intervention and 2069 for control protocol s ) from a systematic sample after assessing their physical activity in routine practice . Intervention physicians provided advice to all patients and a physical activity prescription to the subgroup attending an additional appointment ( 30 % ) . The main outcome measure was the change in physical activity measured by blinded nurses using the 7-Day Physical Activity Recall . Secondary outcomes included cardiorespiratory fitness and health-related quality of life . RESULTS At 6 months , intervention patients increased physical activity more than controls ( adjusted difference , 18 min/wk [ 95 % confidence interval , 6 - 31 min/wk ] ; metabolic equivalent tasks x hours per week , 1.3 [ 95 % CI , 0.4 - 2.2 ] ) . The proportion of the population achieving minimal physical activity recommendations was 3.9 % higher in the intervention group ( 1.2%-6.9 % ; number needed to treat , 26 ) . No differences were found in secondary outcomes . The effect of intervention was positively modified in subjects older than 50 years ( P < or = .01 ) and in the prescription subgroup ( P < .001 ) . CONCLUSIONS Family physicians were effective for increasing physical activity of primary care patients . Overall clinical effect was small but relevant for population public health . Within the intervention program , clinical ly relevant effects were seen in patients receiving a physical activity prescription . Trial Registration clinical trials.gov Identifier : NCT00131079 Background Limited data are available on the development , implementation and evaluation processes of physical activity promotion programmes among older adults . More integrative insights into interventions describing the planned systematic development , implementation and evaluation are needed . Methods and design The purpose of this study is to give an integrative insight into the development of the Active plus programme applying the six-step Intervention Mapping protocol . The Active plus programme consisted of two theory- and evidence -based tailored physical activity promotion interventions , both comprising three tailored letters delivered over four months and aim ed at raising awareness of insufficient physical activity , and stimulating physical activity initiation and maintenance among the over-fifties . The first intervention , the basic tailored intervention , provided tailored letters that intervened on the psychosocial determinants of physical activity . The second intervention , the intervention plus , provided the same tailored information but additionally provided tailored information about physical activity opportunities in the specific environment in which the older adults lived . This environment-based component also provided access to a forum and e-buddy system on a website . A plan for implementation and evaluation is also described . Discussion The planned development of the Active plus programme result ed in two theory- and evidence -based tailored physical activity interventions targeted at the over-fifties . Trial Registration Dutch Trial Register NTR OBJECTIVE We evaluate the 6-month efficacy of Keep Active Minnesota , a phone- and mail-based physical activity maintenance intervention design ed for use with adults age 50 to 70 years who have increased their physical activity within the past year . METHOD Participants ( N=1049 ) recruited in 2004 and 2005 from one large managed-care organization in Minnesota were r and omly assigned to either treatment ( N=523 ) or usual care ( N=526 ) with physical activity assessed using the Community Healthy Activities Model Program for Seniors question naire , and expressed as kcal/week expenditures . RESULTS Total physical activity at baseline was similar for treatment and usual care participants ( p<0.44 ) as was moderate/vigorous physical activity ( p<0.21 ) . Maintenance of physical activity was higher among treatment participants whose mean 6-month change in total kcal/week energy expenditure was -91 , compared to -683 for usual care participants ( p<0.002 ) . Mean 6-month change in kcal/week expenditure in moderate or vigorous activities was -49 for treatment participants , compared to -612 for usual care participants ( p<0.001 ) . CONCLUSIONS This phone- and mail-based physical activity maintenance intervention is efficacious at maintaining physical activity at 6 months Background Scotl and has a policy aim ed at increasing physical activity levels in the population , but evidence on how to achieve this is still developing . Studies that focus on encouraging real world participants to start physical activity in their setting s are needed . The Walking for Well-being in the West study was design ed to assess the effectiveness of a pedometer-based walking programme in combination with physical activity consultation . The study was multi-disciplinary and based in the community . Walking for Well-being in the West investigated whether Scottish men and women , who were not achieving the current physical activity recommendation , increased and maintained walking behaviour over a 12 month period . This paper outlines the rationale and design of this innovative and pragmatic study . Methods Participants were r and omised into two groups : Group 1 : Intervention ( pedometer-based walking programme combined with a series of physical activity consultations ) ; Group 2 : Waiting list control for 12 weeks ( followed by minimal pedometer-based intervention ) . Physical activity ( primary outcome ) was measured using pedometer step counts ( 7 day ) and the International Physical Activity Question naire ( long version ) . Psychological processes were measured using question naires relating to the Transtheoretical Model of Behaviour Change , m Output:	Despite this , there was some indication that the most effective interventions were those that offered both individual and group support for changing PA levels using a tailored approach . Although we found evidence to support the effectiveness of face-to-face interventions for promoting PA , at least at 12 months , the effectiveness of these interventions was not supported by high quality studies . Due to the clinical and statistical heterogeneity of the studies , only limited conclusions can be drawn about the effectiveness of individual components of the interventions .
MS22121	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Proper r and omisation means little if investigators can not include all r and omised participants in the primary analysis . Participants might ignore follow-up , leave town , or take aspartame when instructed to take aspirin . Exclusions before r and omisation do not bias the treatment comparison , but they can hurt generalisability . Eligibility criteria for a trial should be clear , specific , and applied before r and omisation . Readers should assess whether any of the criteria make the trial sample atypical or unrepresentative of the people in which they are interested . In principle , assessment of exclusions after r and omisation is simple : none are allowed . For the primary analysis , all participants enrolled should be included and analysed as part of the original group assigned ( an intent-to-treat analysis ) . In reality , however , losses frequently occur . Investigators should , therefore , commit adequate re sources to develop and implement procedures to maximise retention of participants . Moreover , research ers should provide clear , explicit information on the progress of all r and omised participants through the trial by use of , for instance , a trial profile . Investigators can also do secondary analyses on , for instance , per- protocol or as-treated participants . Such analyses should be described as secondary and non-r and omised comparisons . Mish and ling of exclusions causes serious method ological difficulties . Unfortunately , some explanations for mish and ling exclusions intuitively appeal to readers , disguising the seriousness of the issues . Creative mismanagement of exclusions can undermine trial validity Background Recruiting participants to r and omized controlled trials of health interventions can be very difficult . Internet-based recruitment is becoming an increasingly important mode of recruitment , yet there are few detailed accounts of experiences recruiting participants to mental health interventions . Objective To report on our experience with Internet-based recruitment to an online depression prevention intervention and pass on lessons we learned . Methods Participants were recruited to the Mood Memos study , an online preventive depression intervention , purely through Internet-based sources . The study was targeted to adults with subthreshold depression symptoms from several English-speaking countries . A variety of online recruitment sources were trialed , including search engine advertising ( Google , Yahoo ! , Bing ) , Facebook advertising , posts in forums and online noticeboards , and promotion through relevant websites and email newsletters of mental health organizations . Results The study website received visits from 94,808 individuals over the 14-month recruitment period . The recruitment target was reached with 1699 individuals signing up to the r and omized controlled trial and 1326 fully enrolling . Most visitors arrived via Google advertising , which promoted a depression-screening question naire . Google advertising accounted for nearly half of the total participants who signed up to the study , at an average cost of AUD $ 12 per participant . Promoting the study through trustworthy organizations and websites known to participants was also effective . Recruitment techniques that were less effective were contacting forums , email groups , and community noticeboards . Conclusions Several techniques , including Google advertising , were successful in recruiting participants to a trial evaluating an online depression intervention . Results suggest that Internet-based recruitment to mental health interventions is feasible and can be relatively affordable . Trial Registration Background Under-recruitment to r and omised controlled trials ( RCTs ) is often problematic and there may be particular difficulties in recruiting patients with severe mental illness . Aim To evaluate reasons for under-recruitment in an RCT of patients with severe mental illness Methods Qualitative study during the recruitment phase of an RCT of supported employment . Trial staff and recruiting clinicians were interviewed . Data were analyzed thematically using constant comparative techniques . Results Recruitment rates were low . Five main reasons for recruitment difficulties were found . These included : ( i ) misconceptions about trials , ( ii ) lack of equipoise , ( iii ) misunderst and ing of the trial arms , ( iv ) variable interpretations of eligibility criteria , ( v ) paternalism . Conclusion Reasons for recruitment difficulties in trials involving patients with severe mental illness include issues that occur in trials in general , but others are more specific to these patients . Clinician and patient involvement in the study design may improve recruitment in future similar trials Background Patient and public involvement in research ( PPIR ) may improve trial recruitment rates , but it is unclear how . Where trials use PPIR to improve design and conduct , many do not communicate this clearly to potential participants . Better communication of PPIR might encourage patient enrolment , as trials may be perceived as more socially valid , relevant and trustworthy . We aim ed to evaluate the impact on recruitment of directly advertising PPIR to potential trial participants . Methods This is a cluster trial , embedded within a host trial ( ‘ EQUIP ’ ) recruiting service users diagnosed with severe mental illness . The intervention was informed by a systematic review , a qualitative study , social comparison theory and a stakeholder workshop including service users and carers . Adopting Participatory Design approaches , we co- design ed the recruitment intervention with PPIR partners using a leaflet to advertise the PPIR in EQUIP and sent potential participants invitations with the leaflet ( intervention group ) or not ( control group ) . Primary outcome was the proportion of patients enrolled in EQUIP . Secondary outcomes included the proportions of patients who positively responded to the trial invitation . Results Thirty-four community mental health teams were r and omised and 8182 service users invited . For the primary outcome , 4 % of patients in the PPIR group were enrolled versus 5.3 % of the control group . The intervention was not effective for improving recruitment rates ( adjusted OR = 0.75 , 95 % CI = 0.53 to 1.07 , p = 0.113 ) . For the secondary outcome of positive response , the intervention was not effective , with 7.3 % of potential participants in the intervention group responding positively versus 7.9 % of the control group ( adjusted OR = 0.74 , 95 % CI = 0.53 to 1.04 , p = 0.082 ) . We did not find a positive impact of directly advertising PPIR on any other outcomes . Conclusion To our knowledge , this is the largest ever embedded trial to evaluate a recruitment or PPIR intervention . Advertising PPIR did not improve enrolment rates or any other outcome . It is possible that rather than advertising PPIR being the means to improve recruitment , PPIR may have an alternative impact on trials by making them more attractive , acceptable and patient-centred . We discuss potential reasons for our findings and implication s for recruitment practice and research .Trial registration numbersIS RCT N , IS RCT N16488358 . Registered on 14 May 2014 . Study Within A Trial , SWAT-26 . Registered on 21 January 2016 Background Patient underst and ing of study information is fundamental to gaining informed consent to take part in a r and omised controlled trial . In order to meet the requirements of research ethics committees , patient information material s can be long and need to communicate complex messages . There is concern that st and ard approaches to providing patient information may deter potential participants from taking part in trials . The Systematic Techniques for Assisting Recruitment to Trials ( MRC-START ) research programme aims to test interventions to improve trial recruitment . The aim of this study was to investigate the effect on recruitment of optimised patient information material s ( with improved readability and ease of comprehension ) compared with st and ard material s. The study was embedded within two primary care trials involving patients with long-term conditions . Methods The Healthlines Study involves two linked trials evaluating a telehealth intervention in patients with depression ( Healthlines Depression ) or raised cardiovascular disease risk ( Healthlines CVD ) . We conducted two trials of a recruitment intervention , embedded within the Healthlines host trials . Patients identified as potentially eligible in each of the Healthlines trials were r and omised to receive either the original patient information material s or optimised versions of these material s. Primary outcomes were the proportion of participants r and omised ( Healthlines Depression ) and the proportion expressing interest in taking part ( Healthlines CVD ) . Results In Healthlines Depression ( n = 1364 ) , 6.3 % of patients receiving the optimised patient information material s were r and omised into the study compared to 4.0 % in those receiving st and ard material s ( OR = 1.63 , 95 % CI = 1.00 to 2.67 ) . In Healthlines CVD ( n = 671 ) 24.0 % of those receiving optimised patient information material s responded positively to the invitation to participate , compared to 21.9 % in those receiving st and ard material s ( OR = 1.12 , 95 % CI = 0.78 to 1.61 ) . Conclusions Evidence from these two embedded trials suggests limited benefits of optimised patient information material s on recruitment rates , which may only be apparent in some patient population s , with no effects on other outcomes . Further embedded trials are needed to provide a more precise estimate of effect , and to explore further how effects vary by trial context , intervention , and patient population .Trial registration Current Controlled Trials : Healthlines Depression ( IS RCT N27508731 ) on 26 June 2012 ; and Healthlines CVD ( IS RCT N14172341 ) on 5 July Background Mindfulness interventions to reduce psychological distress are well-suited to pregnancy , due to their brief and non-pharmacological nature , but there is a need for more robust evidence determining their usefulness . This pilot study was design ed to explore the feasibility of a r and omised controlled trial of a mindfulness intervention to reduce antenatal depression , anxiety and stress . Methods The study was design ed in two parts 1 ) a non-r and omised trial targeting women at risk of mental health problems ( a selected population ) and 2 ) a r and omised controlled trial ( RCT ) of a universal population . Process evaluation focused on feasibility of recruitment pathways , participant retention , acceptability of study measures , and engagement with mindfulness practice s. Measurement of psychological distress was taken pre and post intervention through the Centre for Epidemiologic Studies Depression Scale Revised , the Depression Anxiety and Stress Scale-21 , the State-Trait Anxiety Inventory , and the Perceived Stress Scale . Results 20 women were recruited to the non-r and omised trial , and 32 to the RCT . Recruitment through a mailed study brochure at the time of booking-in to the hospital result ed in the largest number of participants in the RCT ( 16/32 ; 50 % ) , and result ed in considerably earlier recruitment ( 50 % in first trimester , 50 % second trimester ) compared to recruitment through the antenatal clinic waiting room ( 86 % in second trimester , 14 % third trimester ) . Over a third of women in the universal population scored above clinical cut-offs for depression and anxiety , indicating a sample with more symptomology than the general population . The most common reason for loss to follow-up was delivery of baby prior to follow-up ( n = 9 ) . In the non-r and omised study , significant within group improvements to depression and anxiety were observed . In the intervention arm of the RCT there were significant within group improvements to anxiety and mindfulness . No between group differences for the intervention and ` care as usual ’ control group were observed . Conclusions This small pilot study provides evidence on the feasibility of an antenatal mindfulness intervention to reduce psychological distress . Major challenges include : finding ways to facilitate recruitment in early pregnancy and engaging younger women and other vulnerable population s . Trial registration Australian New Zeal and Clinical Trials Registry ACTRN12613000742774 ( 31/10/2012 ) OBJECTIVE Our aim was to analyze monetary incentives and shortening the question naire as means of increasing response rates in a mailed follow-up survey 1 year after inpatient psychotherapeutic treatment . Additionally , effects on partial nonresponse and the assessment of treatment outcome were examined . STUDY DESIGN AND SETTING In a 2x2 factorial design , a sample of 3,825 patients was r and omized to the two following interventions : ( 1 ) receiving a prepaid monetary incentive or none ; and ( 2 ) getting a short or a long question naire . Treatment outcome was measured prospect ively by a self- assessment instrument for psychopathology . RESULTS When using incentives , the response rate significantly increased by 7.3 % ( 95 % confidence interval [ CI ] 2.6 - 11.9 % ) . Receiving a short question naire led to an augmentation of the response rate of 3.7 % ( 95 % CI 0.9 - 8.3 % ) , which was not significant . The corresponding odds ratios were significantly increased for monetary incentives ( 1.36 ; 95 % CI 1.30 - 1.88 ) , and when abridging the question naire ( 1.15 ; 95 % CI 1.01 - 1.31 ) . However , partial nonresponse and treatment outcome were independent of the two factors . CONCLUSION Incentives and a shorter question naire led to higher return rates but did not affect partial nonresponse and self-report of treatment outcome in a r and omized postal survey Limitations of printed , text-based , consent forms have long been documented and may be particularly problematic for persons at risk for impaired decision-making capacity , such as those with schizophrenia . We conducted a r and omized controlled comparison of the effectiveness of a multimedia vs routine consent procedure ( augmented with a 10-minute control video presentation ) as a means of enhancing comprehension among 128 middle-aged and older persons with schizophrenia and 60 healthy comparison subjects . The primary outcome measure was manifest decisional capacity ( underst and ing , appreciation , reasoning , and expression of choice ) for participation in a ( hypothetical ) clinical drug trial , as measured with the MacArthur Competence Assessment Tool for Clinical Research ( MacCAT-CR ) and the University of California San Diego ( UCSD ) Brief Assessment for Capacity to Consent ( UBACC ) . The MacCAT-CR and UB Output:	Retrospective comparisons of recruitment methods showed that non-web-based advertisement and recruitment by clinical research staff each have advantages in efficiency . Financial incentives , abridged question naires and pre-notification had a positive effect on retention rates . The recruitment studies included showed differences in strategies , clinical setting s , mental health conditions and study design . It is difficult to assess the overall effectiveness of any particular recruitment strategy as some strategies that worked well for a particular population may not work as well for others . Paying attention to the accessibility of information and consent material s may help improve recruitment .
MS22122	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND A r and omized phase III trial in high-risk breast cancer patients was conducted , to further explore the impact of dose-density in the adjuvant treatment for breast cancer . The safety analysis is presented . PATIENTS AND METHODS From October 2000 until June 2005 , 1121 node-positive patients were r and omized to sequential dose-dense epirubicin 110 mg/m(2 ) and paclitaxel ( Taxol , Bristol Myers-Squibb , Princeton , New Jersey , USA ) 250 mg/m(2 ) ( group A ) , or concurrent epirubicin 83 mg/m(2 ) and paclitaxel 187 mg/m(2 ) ( group B ) , both followed by three cycles of ' intensified ' combination chemotherapy with cyclophosphamide , methotrexate and fluorouracil ( CMF ) . Granulocyte colony-stimulating factor was given prophylactically with the dose-dense treatments . RESULTS Median dose intensity of epirubicin and paclitaxel was double in group A , as design ed , with significantly less cycles administered at full dose ( P < 0.001 ) . Median cumulative dose of all drugs and total treatment duration , however , were identical between groups . Severe taxane-related toxic effects were more frequent in group A , while severe thrombocytopenia was low and present only in group A. There were no differences in the rates of other hematological toxic effects , including febrile neutropenia . The rates of secondary malignancies were low . CONCLUSION Both regimens as used in the present study are well tolerated and safe . The rates of severe taxane-related toxic effects and thrombocytopenia , although low overall , are significantly increased with the dose-dense sequential regimen PURPOSE This study was design ed to determine whether increasing the dose of doxorubicin in or adding paclitaxel to a st and ard adjuvant chemotherapy regimen for breast cancer patients would prolong time to recurrence and survival . PATIENTS AND METHODS After surgical treatment , 3,121 women with operable breast cancer and involved lymph nodes were r and omly assigned to receive a combination of cyclophosphamide ( C ) , 600 mg/m(2 ) , with one of three doses of doxorubicin ( A ) , 60 , 75 , or 90 mg/m(2 ) , for four cycles followed by either no further therapy or four cycles of paclitaxel at 175 mg/m(2 ) . Tamoxifen was given to 94 % of patients with hormone receptor-positive tumors . RESULTS There was no evidence of a doxorubicin dose effect . At 5 years , disease-free survival was 69 % , 66 % , and 67 % for patients r and omly assigned to 60 , 75 , and 90 mg/m(2 ) , respectively . The hazard reductions from adding paclitaxel to CA were 17 % for recurrence ( adjusted Wald chi(2 ) P = .0023 ; unadjusted Wilcoxon P = .0011 ) and 18 % for death ( adjusted P = .0064 ; unadjusted P = .0098 ) . At 5 years , the disease-free survival ( + /- SE ) was 65 % ( + /- 1 ) and 70 % ( + /- 1 ) , and overall survival was 77 % ( + /- 1 ) and 80 % ( + /- 1 ) after CA alone or CA plus paclitaxel , respectively . The effects of adding paclitaxel were not significantly different in subsets defined by the protocol , but in an unplanned subset analysis , the hazard ratio of CA plus paclitaxel versus CA alone was 0.72 ( 95 % confidence interval , 0.59 to 0.86 ) for those with estrogen receptor-negative tumors and only 0.91 ( 95 % confidence interval , 0.78 to 1.07 ) for patients with estrogen receptor-positive tumors , almost all of whom received adjuvant tamoxifen . The additional toxicity from adding four cycles of paclitaxel was generally modest . CONCLUSION The addition of four cycles of paclitaxel after the completion of a st and ard course of CA improves the disease-free and overall survival of patients with early breast cancer BACKGROUND AND OBJECTIVES : Doxorubicin , effective against many malignancies , is limited by cardiotoxicity . Continuous-infusion doxorubicin , compared with bolus-infusion , reduces early cardiotoxicity in adults . Its effectiveness in reducing late cardiotoxicity in children remains uncertain . We determined continuous-infusion doxorubicin cardioprotective efficacy in long-term survivors of childhood acute lymphoblastic leukemia ( ALL ) . METHODS : The Dana-Farber Cancer Institute ALL Consortium Protocol 91 - 01 enrolled pediatric patients between 1991 and 1995 . Newly diagnosed high-risk patients were r and omly assigned to receive a total of 360 mg/m2 of doxorubicin in 30 mg/m2 doses every 3 weeks , by either continuous ( over 48 hours ) or bolus-infusion ( within 15 minutes ) . Echocardiograms at baseline , during , and after doxorubicin therapy were blindly remeasured central ly . Primary outcomes were late left ventricular ( LV ) structure and function . RESULTS : A total of 102 children were r and omized to each treatment group . We analyzed 484 serial echocardiograms from 92 patients ( n = 49 continuous ; n = 43 bolus ) with ≥1 echocardiogram ≥3 years after assignment . Both groups had similar demographics and normal baseline LV characteristics . Cardiac follow-up after r and omization ( median , 8 years ) showed changes from baseline within the r and omized groups ( depressed systolic function , systolic dilation , reduced wall thickness , and reduced mass ) at 3 , 6 , and 8 years ; there were no statistically significant differences between r and omized groups . Ten-year ALL event-free survival rates did not differ between the 2 groups ( continuous-infusion , 83 % versus bolus-infusion , 78 % ; P = .24 ) . CONCLUSIONS : In survivors of childhood high-risk ALL , continuous-infusion doxorubicin , compared with bolus-infusion , provided no long-term cardioprotection or improvement in ALL event-free survival , hence provided no benefit over bolus-infusion A phase II study utilizing VP-16 and adriamycin in a r and omized fashion tested the concept of synchronization of the drugs in treatment of metastatic breast cancer . Although there was a trend in median survival following the synchronized schedule , there was no significant difference in survival or progression-free intervals . The concept of synchronization was not established The Dana-Farber Cancer Institute ( DFCI ) acute lymphoblastic leukemia ( ALL ) Consortium Protocol 91 - 01 was design ed to improve the outcome of children with newly diagnosed ALL while minimizing toxicity . Compared with prior protocol s , post-remission therapy was intensified by substituting dexamethasone for prednisone and prolonging the asparaginase intensification from 20 to 30 weeks . Between 1991 and 1995 , 377 patients ( age , 0 - 18 years ) were enrolled ; 137 patients were considered st and ard risk ( SR ) , and 240 patients were high risk ( HR ) . Following a 5.0-year median follow-up , the estimated 5-year event-free survival ( EFS ) + /- SE for all patients was 83 % + /- 2 % , which is superior to prior DFCI ALL Consortium protocol s conducted between 1981 and 1991 ( P = .03 ) . There was no significant difference in 5-year EFS based upon risk group ( 87 % + /- 3 % for SR and 81 % + /- 3 % for HR , P = .24 ) . Age at diagnosis was a statistically significant prognostic factor ( P = .03 ) , with inferior outcomes observed in infants and children 9 years or older . Patients who tolerated 25 or fewer weeks of asparaginase had a significantly worse outcome than those who received at least 26 weeks of asparaginase ( P < .01 , both univariate and multivariate ) . Older children ( at least 9 years of age ) were significantly more likely to have tolerated 25 or fewer weeks of asparaginase ( P < .01 ) . Treatment on Protocol 91 - 01 significantly improved the outcome of children with ALL , perhaps due to the prolonged asparaginase intensification and /or the use of dexamethasone . The inferior outcome of older children may be due , in part , to increased intolerance of intensive therapy A prospect i ve r and omized trial was conducted to compare the cardiotoxic and therapeutic effects of doxorubicin ( 60 mg/m2 every 3 to 4 weeks ) administered by bolus or 72‐hour continuous infusion as adjuvant chemotherapy in 82 eligible patients after resection of high‐ grade soft tissue sarcoma of the extremity or superficial trunk . Cardiac toxicity , defined as a 10 % or greater decrease in left ventricular ejection fraction as assessed by radionuclide cineangiography , was evaluated in 69 patients . Cardiotoxicity was seen in 61 % of patients in the bolus treatment arm with the median doxorubicin dose of 420 mg/m2 . Among patients who received continuous infusion , 42 % had cardiotoxicity with a median dose of 540 mg/m2 . The rate of cardiotoxicity as a function of the cumulative dose of doxorubicin was significantly higher in the bolus treatment arm ( P = 0.0017 ) . Two patients in each group had clinical congestive heart failure , with one cardiac death occurring in each . There was a trend toward a lower rate of metastasis ( P = 0.19 ) and a significantly lower rate of death of disease ( P = 0.036 ) for patients treated with the bolus dose . Cox model analysis identified three unfavorable characteristics for the rate of developing a distant metastasis : blood transfusion within 24 hours of operation ( P < 0.00001 ) , tumor deep to the fascia and 5 cm or more in size ( P = 0.0043 ) , and a histologic subtype other than liposarcoma ( P = 0.0002 ) . The unfavorable effect of continuous infusion was not selected in the model ( P = 0.16 ) . Adjuvant chemotherapy for patients with soft tissue sarcoma is investigational . Furthermore , the impact of perioperative blood transfusion merits further study PURPOSE Patients with primary breast cancer who have extensive axillary lymph node involvement have a poor prognosis after conventional adjuvant therapy . We compared intense dose-dense ( IDD ) adjuvant chemotherapy with conventionally scheduled adjuvant chemotherapy in patients with high-risk primary breast cancer . PATIENTS AND METHODS In this r and omized , phase III trial , a total of 1,284 eligible patients with four or more involved axillary lymph nodes were r and omly assigned to receive IDD sequential epirubicin , paclitaxel , and cyclophosphamide ( IDD-ETC ) every 2 weeks or conventionally scheduled epirubicin/cyclophosphamide followed by paclitaxel every three weeks . The primary end point was event-free survival ( EFS ) . RESULTS At a median follow-up of 62 months , 5-year event-free survival rates were 62 % in the conventional arm and 70 % in the IDD-ETC arm , representing a 28 % reduction of the relative risk of relapse ( P < .001 ) . This benefit was independent of menopausal , hormone receptor , or human epidermal growth factor receptor 2 status . The 5-year overall survival rates were 77 % versus 82 % , representing a 24 % reduction of the relative risk of death ( P = .0285 ) . IDD therapy was associated with significantly more nonhematologic and hematologic toxicities , but no treatment-related death occurred . Four occurrences of acute myeloid leukemia or myelodysplastic syndrome ( MDS ) were observed in the IDD-ETC arm . No severe congestive heart failure was reported . CONCLUSION IDD-ETC was less well tolerated compared with conventional chemotherapy but significantly improved event-free and overall survivals in patients with high-risk primary breast cancer who had four or more positive axillary lymph nodes Forty-eight patients with advanced breast carcinoma who had not received prior chemotherapy ( minimum follow up 21 months ) were r and omised to receive either adriamycin 70 mg m-2 i.v . 3-weekly for 8 cycles ( Regimen A ) or adriamycin 35 mg m-2 i.v . 3-weekly for 16 courses ( Regimen B ) . Objective responses were seen in 14/24 ( 58 % ) patients with regimen A ( 4 complete ) and 6/24 ( 25 % ) with regimen B ( 1 complete ) ( P less than 0.02 ) . The median duration of response was 14 months with regimen A and 6.5 months with regimen B. The median duration of survival was 20 months and 8 months respectively ( P less than 0.01 ) . The toxicity was similar with each reg Output:	An anthracycline infusion duration of six hours or longer reduces the risk of clinical heart failure , and it seems to reduce the risk of sub clinical cardiac damage .
MS22123	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE Despite the frequent use of the Positive and Negative Syndrome Scale ( PANSS ) for rating the symptoms of schizophrenia , the clinical meaning of its total score and of the cut-offs that are used to define treatment response ( e.g. at least 20 % or 50 % reduction of the baseline score ) are as yet unclear . We therefore compared the PANSS with simultaneous ratings of Clinical Global Impressions ( CGI ) . METHOD PANSS and CGI ratings at baseline ( n = 4091 ) , and after one , two , four and six weeks of treatment taken from a pooled data base of seven pivotal , multi-center antipsychotic drug trials on olanzapine or amisulpride in patients with exacerbations of schizophrenia were compared using equipercentile linking . RESULTS Being considered " mildly ill " according to the CGI approximately corresponded to a PANSS total score of 58 , " moderately ill " to a PANSS of 75 , " markedly ill " to a PANSS of 95 and severely ill to a PANSS of 116 . To be " minimally improved " according to the CGI score was associated with a mean percentage PANSS reduction of 19 % , 23 % , 26 % and 28 % at weeks 1 , 2 , 4 and 6 , respectively . The corresponding figures for a CGI rating " much improved " were 40 % , 45 % , 51 % and 53 % . CONCLUSIONS The results provide a better framework for underst and ing the clinical meaning of the PANSS total score in drug trials of schizophrenia patients with acute exacerbations . Such studies may ideally use at least a 50 % reduction from baseline cut-off to define response rather than lower thresholds . In treatment resistant population s , however , even a small improvement can be important , so that a 25 % cut-off might be appropriate Overwhelming evidence shows the quality of reporting of r and omised controlled trials ( RCTs ) is not optimal . Without transparent reporting , readers can not judge the reliability and validity of trial findings nor extract information for systematic review s. Recent method ological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects . Such systematic error is seriously damaging to RCTs , which are considered the gold st and ard for evaluating interventions because of their ability to minimise or avoid bias . A group of scientists and editors developed the CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to improve the quality of reporting of RCTs . It was first published in 1996 and up date d in 2001 . The statement consists of a checklist and flow diagram that authors can use for reporting an RCT . Many leading medical journals and major international editorial groups have endorsed the CONSORT statement . The statement facilitates critical appraisal and interpretation of RCTs . During the 2001 CONSORT revision , it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports . A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement . After an expert meeting in January 2007 , the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement . This up date improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition , such as selective outcome reporting bias . This explanatory and elaboration document-intended to enhance the use , underst and ing , and dissemination of the CONSORT statement-has also been extensively revised . It presents the meaning and rationale for each new and up date d checklist item providing examples of good reporting and , where possible , references to relevant empirical studies . Several examples of flow diagrams are included . The CONSORT 2010 Statement , this revised explanatory and elaboration document , and the associated website ( www.consort-statement.org ) should be helpful re sources to improve reporting of r and omised trials The authors estimated components of variance and intraclass correlation coefficients ( ICCs ) to aid in the design of complex surveys and community intervention studies by analyzing data from the Health Survey for Engl and 1994 . This cross-sectional survey of English adults included data on a range of lifestyle risk factors and health outcomes . For the survey , households were sample d in 720 postal code sectors nested within 177 district health authorities and 14 regional health authorities . Study subjects were adults aged 16 years or more . ICCs and components of variance were estimated from a nested r and om-effects analysis of variance . Results are presented at the district health authority , postal code sector , and household levels . Between-cluster variation was evident at each level of clustering . In these data , ICCs were inversely related to cluster size , but design effects could be substantial when the cluster size was large . Most ICCs were below 0.01 at the district health authority level , and they were mostly below 0.05 at the postal code sector level . At the household level , many ICCs were in the range of 0.0 - 0.3 . These data may provide useful information for the design of epidemiologic studies in which the units sample d or allocated range in size from households to large administrative areas OBJECTIVE This 6-week trial assessed the efficacy , tolerability , and safety of the investigational psychopharmacologic agent asenapine versus placebo and risperidone in patients with acute schizophrenia ( DSM-IV criteria ) . METHOD In a study conducted from August 2001 to May 2002 , patients were r and omly assigned to receive sublingual asenapine 5 mg b.i.d . , placebo b.i.d . , or oral risperidone 3 mg b.i.d . The primary outcome measure was improvement from baseline in Positive and Negative Syndrome Scale ( PANSS ) total score . Secondary outcomes included changes in Clinical Global Impressions-Severity of Illness ( CGI-S ) score and scores on PANSS positive , negative , and general psychopathology subscales . RESULTS The intent-to-treat population comprised 174 patients who received > or= 1 dose of study drug and > or= 1 postbaseline assessment . At study end or last observation , mean improvements on PANSS total , negative subscale , and general psychopathology subscale scores were all significantly greater with asenapine than with placebo ( p < .005 , p = .01 , and p < .005 , respectively ) . Compared with placebo , improvements on CGI-S and PANSS positive subscale scores were significantly greater with both asenapine ( p < .01 and p = .01 ) and risperidone ( p < .005 and p < .05 ) . Overall incidence rates of adverse events were comparable for asenapine and placebo , whereas risperidone was associated with substantial weight gain and prolactin elevation . CONCLUSION Asenapine was effective and well tolerated in patients with acute schizophrenia and may provide a new option for control of negative symptoms OBJECTIVE Long-term efficacy of asenapine in preventing schizophrenia relapse was assessed in a 26-week double-blind , placebo-controlled trial that followed 26 weeks of open-label treatment . METHOD Stable schizophrenia patients ( DSM-IV-TR criteria ) who were cross-titrated from previous medication to sublingual asenapine and remained stable during 26 weeks of open-label treatment were eligible for 26 weeks of double-blind treatment , with r and omization to continued asenapine or switch to placebo . Time to relapse/impending relapse ( primary endpoint , as usually determined by specific scores on the Positive and Negative Syndrome Scale and the Clinical Global Impressions-Severity of Illness Scale ) and discontinuation for any reason ( key secondary endpoint ) were assessed by survival analyses for asenapine versus placebo . The study was conducted from May 2005 through June 2008 . RESULTS Of 700 enrolled patients treated with open-label asenapine , 386 entered ( asenapine , n = 194 ; placebo , n = 192 ) and 207 completed ( n = 135 ; n = 72 ) the double-blind phase . Times to relapse/impending relapse and discontinuation for any reason were significantly longer with asenapine than with placebo ( both P < .0001 ) . Incidence of relapse/impending relapse was lower with asenapine than placebo ( 12.1 % vs 47.4 % , P < .0001 ) . The modal dosage of asenapine was 10 mg twice daily in both phases . During the double-blind phase , the incidence of adverse events ( AEs ) considered serious with asenapine and placebo was 3.1 % and 9.9 % , respectively ; incidence of extrapyramidal symptom-related AEs was 3.1 % and 4.7 % , respectively . The most frequently reported AEs with asenapine versus placebo were anxiety ( 8.2 % ; 10.9 % ) , increased weight ( 6.7 % ; 3.6 % ) , and insomnia ( 6.2 % ; 13.5 % ) . The incidence of clinical ly significant weight gain ( ≥ 7 % increase from double-blind baseline ) was 3.7 % with asenapine and 0.5 % with placebo . CONCLUSIONS Long-term treatment with asenapine was more effective than placebo in preventing relapse of schizophrenia and appeared to be safe and well tolerated . TRIAL REGISTRATION clinical trials.gov Identifier NCT00150176 BACKGROUND In two double-blind trials conducted in North America , 513 patients with chronic schizophrenia received risperidone , haloperidol , or placebo . In the present study , combined data from the two trials were analyzed . METHOD Patients were r and omly assigned to receive placebo , fixed doses of risperidone ( 2 , 6 , 10 , and 16 mg/day ) or 20 mg/day of haloperidol for 8 weeks . Factor analysis of scores on the Positive and Negative Syndrome Scale ( PANSS ) produced five dimensions ( negative symptoms , positive symptoms , disorganized thought , uncontrolled hostility/excitement , and anxiety/depression ) , similar to the five dimensions of previous factor-analytic studies of PANSS data . RESULTS Mean changes ( symptom reductions ) in PANSS factor scores from baseline to treatment Weeks 6 and 8 were significantly greater in patients receiving 6 - 16 mg/day of risperidone than in patients receiving placebo or haloperidol . The advantages of risperidone were greatest for negative symptoms , uncontrolled hostility/excitement , and anxiety/depression . Even at the lowest dose , 2 mg/day , risperidone was significantly ( p < or = .05 ) superior to haloperidol in reducing negative symptoms . The differences in outcomes between risperidone and haloperidol on PANSS scores were not related to extrapyramidal symptoms . CONCLUSION Risperidone produced significantly ( p < or = .05 ) greater improvements than haloperidol on all five dimensions . The large between-group differences on negative symptoms , hostility/excitement , and anxiety/depression suggest that risperidone and other serotonin/dopamine antagonists have qualitatively different effects from those of conventional antipsychotic agents A modification of an earlier rating scale for extrapyramidal system disturbance is described , and evidence for the validity and reliability of the scale is presented . The usefulness of the scale in studies of neuroleptic drugs is discussed . By its application it is possible to quantify extrapyramidal side effects and to separate them into four principal factors BACKGROUND A recent review suggested an association between using unpublished scales in clinical trials and finding significant results . AIMS To determine whether such an association existed in schizophrenia trials . METHOD Three hundred trials were r and omly selected from the Cochrane Schizophrenia Group 's Register . All comparisons between treatment groups and control groups using rating scales were identified . The publication status of each scale was determined and cl aims of a significant treatment effect were recorded . RESULTS Trials were more likely to report that a treatment was superior to control when an unpublished scale was used to make the comparison ( relative risk 1.37 ( 95 % CI 1.12 - 1.68 ) ) . This effect increased when a ' gold-st and ard ' definition of treatment superiority was applied ( RR 1.94 ( 95 % CI 1.35 - 2.79 ) ) . In non-pharmacological trials , one-third of ' gold-st and ard ' cl aims of treatment superiority would not have been made if published scales had been used . CONCLUSIONS Unpublished scales are a source of bias in schizophrenia trials Overwhelming evidence shows the quality of reporting of r and omised controlled trials ( RCTs ) is not optimal . Without transparent reporting , readers can not judge the reliability and validity of trial findings nor extract information for systematic review s. Recent method ological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects . Such systematic error is seriously damaging to RCTs , which are considered the gold st and ard for evaluating interventions because of their ability to minimise or avoid bias . A group of scientists and editors developed the CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to improve the quality of reporting of RCTs . It was first published in 1996 and up date d in 2001 . The statement consists of a checklist and flow diagram that authors can use for reporting an RCT . Many leading medical journals and major international editorial groups have endorsed the CONSORT statement . The statement facilitates critical appraisal and interpretation of RCTs . During the 2001 CONSORT revision , it became clear that explanation Output:	AUTHORS ' CONCLUSIONS There is some , albeit preliminary , evidence that asenapine provides an improvement in positive , negative , and depressive symptoms , whilst minimising the risk of adverse effects . However due to the low- quality and limited quantity of evidence , it remains difficult to recommend the use of asenapine for people with schizophrenia .
MS22124	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To evaluate the feasibility , acceptability , and efficacy of an after-school team sports program for reducing weight gain in low-income overweight children . DESIGN Six-month , 2-arm , parallel-group , pilot r and omized controlled trial . SETTING Low-income , racial/ethnic minority community . PARTICIPANTS Twenty-one children in grade s 4 and 5 with a body mass index at or above the 85th percentile . INTERVENTIONS The treatment intervention consisted of an after-school soccer program . The " active placebo " control intervention consisted of an after-school health education program . MAIN OUTCOME MEASURES Implementation , acceptability , body mass index , physical activity measured using accelerometers , reported television and other screen time , self-esteem , depressive symptoms , and weight concerns . RESULTS All 21 children completed the study . Compared with children receiving health education , children in the soccer group had significant decreases in body mass index z scores at 3 and 6 months and significant increases in total daily , moderate , and vigorous physical activity at 3 months . CONCLUSION An after-school team soccer program for overweight children can be a feasible , acceptable , and efficacious intervention for weight control The optimal exercise modality for reductions of abdominal obesity and risk factors for type 2 diabetes in youth is unknown . We examined the effects of aerobic exercise ( AE ) versus resistance exercise ( RE ) without caloric restriction on abdominal adiposity , ectopic fat , and insulin sensitivity and secretion in youth . Forty-five obese adolescent boys were r and omly assigned to one of three 3-month interventions : AE , RE , or a nonexercising control . Abdominal fat was assessed by magnetic resonance imaging , and intrahepatic lipid and intramyocellular lipid were assessed by proton magnetic resonance spectroscopy . Insulin sensitivity and secretion were evaluated by a 3-h hyperinsulinemic-euglycemic clamp and a 2-h hyperglycemic clamp . Both AE and RE prevented the significant weight gain that was observed in controls . Compared with controls , significant reductions in total and visceral fat and intrahepatic lipid were observed in both exercise groups . Compared with controls , a significant improvement in insulin sensitivity ( 27 % ) was observed in the RE group . Collapsed across groups , changes in visceral fat were associated with changes in intrahepatic lipid ( r = 0.72 ) and insulin sensitivity ( r = −0.47 ) . Both AE and RE alone are effective for reducing abdominal fat and intrahepatic lipid in obese adolescent boys . RE but not AE is also associated with significant improvements in insulin sensitivity Background / aim Resistance training is an exercise modality at which overweight and obese adolescents can excel and which can therefore positively affect their psychological well-being . The aim of this study was to determine the effect of a 6-month resistance training intervention on the self-concept strength and body composition of overweight and obese adolescent males . Methods 56 overweight and obese males aged 13–17 years were r and omly allocated to an Intervention ( n=30 ) or Control ( n=26 ) group . Primary ( psychological ) and secondary ( strength and body composition ) outcomes were assessed at baseline as well as at 3 ( halfway through the intervention ) , 6 ( immediately postintervention ) and 12 months follow-up . R and om effects mixed modelling was used to determine the effects of the intervention . Results Statistically significant differences between the Intervention and Control groups were observed at 3-month and 6-month assessment s for exercise self-efficacy , resistance training confidence and self-esteem . Large increases in strength for the Intervention group , relative to Controls , were also observed with no substantial changes in body composition shown for either group . Values for all variables returned to baseline following completion of the programme . Conclusions A 6-month resistance training intervention can positively affect the self-concept and strength of overweight and obese adolescent boys BACKGROUND Sedentary activities such as video gaming are independently associated with obesity . Active video games , in which players physically interact with images on screen , may help increase physical activity and improve body composition . OBJECTIVE The aim of this study was to evaluate the effect of active video games over a 6-mo period on weight , body composition , physical activity , and physical fitness . DESIGN We conducted a 2-arm , parallel , r and omized controlled trial in Auckl and , New Zeal and . A total of 322 overweight and obese children aged 10 - 14 y , who were current users of sedentary video games , were r and omly assigned at a 1:1 ratio to receive either an active video game up grade package ( intervention , n = 160 ) or to have no change ( control group , n = 162 ) . The primary outcome was the change from baseline in body mass index ( BMI ; in kg/m(2 ) ) . Secondary outcomes were changes in percentage body fat , physical activity , cardiorespiratory fitness , video game play , and food snacking . RESULTS At 24 wk , the treatment effect on BMI ( -0.24 ; 95 % CI : -0.44 , -0.05 ; P = 0.02 ) favored the intervention group . The change ( ±SE ) in BMI from baseline increased in the control group ( 0.34 ± 0.08 ) but remained the same in the intervention group ( 0.09 ± 0.08 ) . There was also evidence of a reduction in body fat in the intervention group ( -0.83 % ; 95 % CI : -1.54 % , -0.12 % ; P = 0.02 ) . The change in daily time spent playing active video games at 24 wk increased ( 10.03 min ; 95 % CI : 6.26 , 13.81 min ; P < 0.0001 ) with the intervention accompanied by a reduction in the change in daily time spent playing nonactive video games ( -9.39 min ; 95 % CI : -19.38 , 0.59 min ; P = 0.06 ) . CONCLUSION An active video game intervention has a small but definite effect on BMI and body composition in overweight and obese children . This trial was registered in the Australian New Zeal and Clinical Trials Registry at http://www.anzctr.org.au/ as ACTRN12607000632493 OBJECTIVES The primary goals of this study were to determine the effects of a physical activity intervention on the set-shifting aspect of executive function and to explore the potential mechanistic role of cardiac autonomic control , as assessed by heart rate variability ( HRV ) , in the relationship between physical activity and executive function in obese young adolescents . METHOD Obese young adolescents were r and omized either to participate in a physical activity program ( n = 25 ) or to serve as the wait-list control ( n = 25 ) for a 3-month intervention . Outcome measures included physical fitness , obesity status , executive function , and HRV ; these measures were assessed at baseline and within 1 week of the conclusion of the intervention . RESULTS The physical activity program improved the participants ' physical fitness and obesity status . The program also improved executive function-related set-shifting performance , as measured by the total number of errors , and increased the HRV indices of normalized low frequency ( nLF ) and normalized high frequency ( nHF ) . A positive correlation between the nHF time changes and the total number of errors was also observed . CONCLUSION These findings suggest that 3 months of a physical activity intervention effectively increase physical fitness and improve the set-shifting aspect of executive function in obese young adolescents . Furthermore , the physical activity-related alterations in cardiac autonomic control , particularly the parasympathetic response , may be associated with enhanced executive function . ( PsycINFO Data base BACKGROUND Structured exergaming with prescribed moderate intensity physical activity has reduced adiposity among adolescents . The extent to which adolescents reduce adiposity when allowed to self-select intensity level is not known . OBJECTIVE The objective of the study was to examine the influence of exergaming on adolescent girls ' body composition and cardiovascular risk factors . METHODS This r and omized controlled trial assigned 41 overweight and obese girls aged 14 to 18 years to group-based dance exergaming ( 36 h over 3 months ) or to a self-directed care control condition . Body size and composition were measured by anthropometry , dual-energy X-ray absorptiometry [ % fat and bone mineral density { BMD } ] and magnetic resonance imaging . Cardiovascular risk factors included blood pressure , cholesterol , triglycerides , glucose and insulin . RESULTS Attrition was 5 % . Using analysis of covariance controlling for baseline value , age and race , there were no significant condition differences . Per protocol ( attended > 75 % ) , the intervention group significantly decreased abdominal subcutaneous adiposity and increased trunk and spine BMD ( ps < 0.05 ) . Per protocol ( > 2600 steps/session ) , the intervention group significantly decreased leg % fat and decreased abdominal subcutaneous and total adiposity ( ps < 0.05 ) . CONCLUSION Exergaming reduced body fat and increased BMD among those adolescent girls who adhered . Further research is required before exergaming is recommended in clinical setting AIM To determine whether five months of guided active play in overweight or obese children and adolescents under multi-disciplinary management for weight reduction leads to increased physical activity levels in leisure time , as well as changes in aerobic fitness and body composition . METHODS Sixty overweight or obese children and adolescents were r and omly assigned to an intervention or control group . All participants received dietary advice and were encouraged to increase physical activity level . The intervention group additionally participated in 60-minute guided active play/physical activity twice a week for 5 months . Physical activity was recorded ; aerobic fitness and body composition were measured at inclusion and after cessation of intervention . RESULTS Physical activity level during weekend days was significantly higher for the intervention group compared with the controls after 5 months intervention ( p=0.04 ) . The mean reduction in percentage of body fat was 1.8 % ( 95%CI : 0.6 , 3.1 ) in the intervention group ( p=0.04 ) and not significant among the controls ( 0.9 [ -0.9 , 2.7 ] ) . There was no change in aerobic fitness . CONCLUSION Five months of guided active play was associated with increased physical activity levels during weekend days and reduced body fat , although weakly , in overweight and obese children and adolescents participating in multi-disciplinary weight reduction programmes Adjustments for making multiple comparisons in large bodies of data are recommended to avoid rejecting the null hypothesis too readily . Unfortunately , reducing the type I error for null associations increases the type II error for those associations that are not null . The theoretical basis for advocating a routine adjustment for multiple comparisons is the “ universal null hypothesis ” that “ chance ” serves as the first-order explanation for observed phenomena . This hypothesis undermines the basic premises of empirical research , which holds that nature hollows regular laws that may he studied through observations . A policy of not making adjustments for multiple comparisons is preferable because it will lead to fewer errors of interpretation when the data under evaluation are not r and om numbers but actual observations on nature . Furthermore , scientists should not he so reluctant to explore leads that may turn out to he wrong that they penalize themselves by missing possibly important findings PURPOSE We assessed the exercise tolerance and cardiorespiratory responses during 2-month weight-loss programmes using the 6-minute walking test ( 6MWT ) in obese children . METHODS Twenty-eight male obese children were r and omly assigned to either a control group ( C ) , an energy restriction group ( R ) , an exercise training at maximum lipid-oxidation ( LIPOXmax ) group ( E ) , or an energy restriction/training group ( RE ) . The body composition , the submaximal incremental cycling exercise , and the 6MWT were performed before and after the 2-month programme . RESULTS . After the programme , RE group showed a significant improvement of body composition ( body weight reduced by 6.3 ± 1.5 kg , p < 0.01 ) , and an increase of 6-minute walking distance ( 6MWD ) ( + 13.7 % , p < 0.01 ) . Similarly , maximum oxygen uptake calculated according to the American College of Science Medicine guideline ( VO(2max ) ACSM ) and VO(2max ) predicted from 6MWD were respectively higher ( + 12.9 % and + 10.0 % , p < 0.01 ) than the R or E groups . Bl and -Altman analysis highlighted an agreement of these two methods of VO(2max ) measurement . Moreover , in all participants the 6MWD was significantly correlated with VO(2max ) ACSM and LIPOXmax ( r = 0.77 , p < 0.001 and r = 0.67 , p < 0.01 ; respectively ) before the programme as well as their changes in percentage over the programme ( r = 0.85 and r = 0.86 , p < 0.0001 ; respectively ) . CONCLUSIONS We concluded that a 2-month weight-loss programme including energy restriction and exercise training targeted at LIPOXmax improved body composition and cardiorespiratory tolerance in obese children . Furthermore , the 6MWT could be considered as a useful and reliable tool for the assessment and the follow-up of cardiorespiratory responses during weight-loss programme in obese children OBJECTIVES We sought to characterize the impact of obesity on vascular function in adolescents and to determine whether an exercise program reverses abnormalities in endothelial function . BACKGROUND Obesity , a major modifiable risk factor for cardiovascular disease , is epidemic in Western societies , with rapid rates of increase in the young . Ather Output:	Combined aerobic and strength training was ranked first for improving both fat mass ( kg ) and per cent body fat while aerobic exercise was ranked first for improving BMI . Conclusions Aerobic and combined aerobic and strength training are associated with improvements in adiposity outcomes in overweight and obese children and adolescents .
MS22125	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background and aims Manual laboratory continuous positive airway pressure ( CPAP ) titration for obstructive sleep apnoea ( OSA ) is costly , time intensive and delays access to treatment . Automatic positive airway pressure ( APAP ) titration has the potential to reduce cost and improve access to treatment . The aim of this study was to assess the clinical efficacy and costs of APAP titration compared with manual titration in moderate – severe OSA . Methods Patients with moderate – severe OSA ( apnoea/hypopnoea index > 15 and Epworth Sleepiness Score ≥8 ) who were free of co-morbidities that could impair APAP titration were eligible . 249 participants were r and omised to manual titration , home APAP or laboratory APAP titration to determine a fixed pressure for CPAP . Clinical and direct cost outcomes were assessed after 4 weeks of treatment . Results Average nightly CPAP use , subjective sleepiness , SF36 quality of life , Trails A and B cognitive function and polysomnographic outcomes were similar among the per- protocol groups . Non-hypertensive patients had a lower resting heart rate ( and greater reduction in heart rate ) at 4 weeks after laboratory APAP titration compared with home APAP titration . Costs per patient were highest in manual ( AU$817.84 ) , followed by laboratory ( AU$647.56 ) and home ( AU$132.09 ) APAP titration . An intention-to-treat analysis confirmed the effectiveness of APAP titration compared with manual titration in the st and ard clinical setting . Conclusions Among patients with moderate – severe OSA without serious co-morbidities , outcomes at 1 month indicate that APAP titration is more cost-effective than manual laboratory titration to determine an appropriate pressure for CPAP for long-term use ; with the largest savings occurring in the home APAP patients . Australian New Zeal and Clinical Trials Registry Number ACTRN12608000054314 BACKGROUND Obstructive sleep apnea syndrome ( OSAS ) has been associated with increased morbidity and mortality , principally from cardiovascular disease , but the impact of nasal continuous positive airway pressure ( CPAP ) therapy is unclear . METHODS We performed a long-term follow-up study of 168 patients with OSAS who had begun receiving CPAP therapy at least 5 years previously , most of whom had been prospect ively followed up , having been the subject of an earlier report on cardiovascular risk factors in OSAS patients . The average follow-up period was 7.5 years . We compared the cardiovascular outcomes of those patients who were intolerant of CPAP ( untreated group , 61 patients ) with those continuing CPAP therapy ( 107 patients ) . RESULTS CPAP-treated patients had a higher median apnea-hypopnea index score than the untreated group ( 48.3 [ interquartile range ( IQR ) , 33.6 to 66.4 ] vs 36.7 [ IQR , 27.4 to 55 ] , respectively ; p = 0.02 ) , but age , body mass index , and time since diagnosis were similar . Deaths from cardiovascular disease were more common in the untreated group than in the CPAP-treated group during follow-up ( 14.8 % vs 1.9 % , respectively ; p = 0.009 [ log rank test ] ) , but no significant differences were found in the development of new cases of hypertension , cardiac disorder , or stroke . Total cardiovascular events ( ie , death and new cardiovascular disease combined ) were more common in the untreated group than in the CPAP-treated group ( 31 % vs 18 % , respectively ; p < 0.05 ) . CONCLUSIONS The data support a protective effect of CPAP therapy against death from cardiovascular disease in patients with OSAS OBJECTIVES To study the effects of augmentation of continuous positive airway pressure ( CPAP ) education and support on compliance and outcome in patients with obstructive sleep apnea ( OSA ) . DESIGN A r and omized , controlled , parallel study of basic vs augmented CPAP education and support . SETTING A university teaching hospital . PATIENTS A total of 108 OSA patients r and omized into basic-support ( BS ) and augmented-support ( AS ) groups . INTERVENTIONS Patients in the BS group ( n = 54 ) were given educational brochures on OSA and CPAP , CPAP education by nurses , CPAP acclimatization , and were review ed by physicians and nurses at weeks 4 and 12 . Patients in the AS group ( n = 54 ) received more education , including a videotape , telephone support by nurses , and early review at weeks 1 and 2 . MEASUREMENTS Objective CPAP compliance , Calgary sleep apnea quality of life index ( SAQLI ) , and cognitive function after 1 month and 3 months ; and Epworth sleepiness scale ( ESS ) after 3 months of CPAP treatment . RESULTS At 4 weeks , CPAP usage was 5.3 + /- 0.2 h/night ( mean + /- SEM ) vs 5.5 + /- 0.2 h/night in the BS and AS groups , respectively ( p = 0.4 ) . At 12 weeks , CPAP usage was 5.3 + /- 0.3 h/night vs 5.3 + /- 0.2 h/night in the two groups , respectively ( p = 0.98 ) . There was greater improvement of SAQLI at 4 weeks ( p = 0.008 ) and at 12 weeks ( p = 0.047 ) in the AS group . There was no significant difference between BS and AS groups in terms of improvement of ESS and cognitive function . CONCLUSION Augmentation of CPAP education and support does not increase CPAP compliance , but leads to a greater improvement of quality of life during the reinforced period Background Following the World Trade Center disaster , a large number of individuals involved in rescue and recovery activity were exposed to significant amounts of dust , and reported symptoms of chronic nasal and sinus inflammation . An unusually high prevalence of obstructive sleep apnea ( OSA ) has also been observed in this World Trade Center Responder population . This project aims to examine the relationship between nasal pathology and OSA . Our hypothesis is that increased nasal resistance due to nasal inflammation predisposes to OSA in this population . Continuous Positive Airway Pressure ( CPAP ) is the st and ard therapy for OSA but despite its efficacy has poor adherence . Subjects with high nasal resistance may have greater difficulty in tolerating this therapy than those who do not have high nasal resistance . Reduction of excess expiratory positive pressure by the modality known as Cflex ™ during Continuous Positive Airway Pressure therapy ( CPAPFlex ) has been suggested to improve comfort without compromising efficacy . We will compare CPAP to CPAPFlex in subjects with OSA . Study Design Subjects with new onset habitual snoring will be screened for OSA using home sleep studies and rhinomanometry will be used to determine nasal resistance . In 400 subjects with OSA we will perform a r and omized double blind cross-over study comparing CPAP to CPAPflex , and relate nasal resistance to adherence to CPAP therapy . Discussion This is the first multicenter trial design ed to test the hypothesis that adherence to CPAP therapy relates to nasal resistance and CPAPFlex will improve adherence to CPAP in those subjects with high nasal resistance . We anticipate the following results from this trial : 1 . Increased nasal resistance is associated with decreased adherence to CPAP therapy . 2 . Use of CPAPFlex improves adherence with CPAP therapy in subjects with high nasal resistance , but not in those with low nasal resistance . 3 . The benefit of CPAPFlex on adherence is greatest when offered at CPAP therapy initiation rather than as a “ rescue ” therapy in subjects with high nasal resistance . Trial Registration Clinical Trials.gov Identifier : NCT01753999 , Date : 12 December STUDY OBJECTIVES To compare conventional and self-adjusting nasal continuous positive airway pressure ( nCPAP ) therapy in patients with severe obstructive sleep apnea syndrome with respect to suppression of respiratory disturbances , quality of sleep , mean mask pressure , and patient compliance . DESIGN Cohort study of consecutive patients with obstructive sleep apnea syndrome , single-blinded . SETTING Clinical sleep laboratory in Germany . PATIENTS Fifty patients ( 44 men , 6 women who ranged in age from 35 to 71 years ) with polysomnographically confirmed severe obstructive sleep apnea syndrome ( respiratory disturbance index [ RDI ] , > 20/h ) . MEASUREMENTS AND INTERVENTIONS After baseline polysomnography , patients were r and omly treated with nCPAP either in conventional ( group 1 ) or in automatically adjusting ( group 2 ) mode . Three to 6 months after adjustment , all patients underwent polysomnography again . They also were examined with a portable monitoring device and received a question naire on subjective well-being and device evaluation . RESULTS Anthropometric and respiratory data were comparable in both groups ; body mass index had not changed significantly in the follow-up . RDI dropped by 91.5 % ( from 38.3+/- 13.9/h to 3.6+/-4.4/h ) in conventional and by 93.6 % ( from 35.5+/-9.6/h to 2.4+/-1.6/h ) in self-adjusting mode ( statistically not significant [ NS ] ) . Sleep efficiency decreased by 4.0 % in conventional and increased by 2.0 % in self-adjusting mode ( NS ) . In both groups , normal sleep structure was largely restored . Mean mask pressure was 8.1+/-2.5 cm H2O in group 1 and 6.5+/-1.7 cm H2O in group 2 ( p<0.01 ) . Patient compliance in terms of nights per week of mask appliance was better in the self-adjusting mode ( 5.7+/-0.7 to 6.5+/-0.4 ; p<0.01 ) . CONCLUSION Self-adjusting nCPAP demonstrates the same reliability in suppression of respiratory disturbances as fixed-mask pressure therapy . Sleep quality is slightly superior , patient compliance is highly significantly better The first generation of Auto CPAP devices caused respiratory arousal by apnoes , hypopnoeas , incomplete obstructions and pressurechanges . The new , second generation of CPAP devices which is based on forced oscillation technique will change the pressure with slower velocity and before the respiratory arousal reaction will occur ( 1 , 9 , 10 ) . Fifty patients with severe sleep apnoea ( AHI 66±26 /h ) were treated with both , constant- CPAP ( continous positive airway pressure ) or Auto CPAP under polysomnographic control in a r and omised order . The Auto CPAP based on forced oscillation technique reduced the number of apnoeas and hypopnoeas as did most of the other Auto CPAP systems to AHI 2.5±5.9 /h ( p<0.05 ) . In comparison to Auto CPAP of the first generation it also decreased the number of respiratory arousal reactions caused by apnoeas and hypopnoeas . However there is still a significant difference to number of arousal detected with constant CPAP ( p<0.01 ) . In conclusion although the new generation of Auto CPAP reduced the number of respiratory arousals compared to first generation , we did not find a therapeutical benefit for patients with severe SAS Daytime CPAP titration studies with full polysomnography have been successfully performed in patients with severe sleep apnea-hypopnea syndrome ( SAHS ) . The implementation of daytime studies in unselected SAHS patients could help to reduce the waiting lists for CPAP titrations . The main purpose of this study was to compare the effectiveness of conventional versus manual or automatic daytime CPAP titration in unselected patients with SAHS . Ninety-three consecutive patients with SAHS in whom CPAP was indicated were assigned to conventional titration or to manual or automatic ( AutoSet ) daytime CPAP titration , after sleep deprivation . The number of valid studies , sleep architecture , final pressure selected and mean pressure in the different sleep stages were compared . Changes in sleepiness ( Epworth sleepiness score ) and hours of CPAP use were assessed after 3 months of treatment . Four patients did not sleep ( 3 AutoSet , 1 conventional daytime groups ) . Sleep latency was shorter during automatic daytime titration whereas REM latency was shorter in daytime studies ; the percentage of sleep stages was similar during all types of titration . CPAP requirements were significantly higher during REM sleep in conventional and manual daytime titrations while mean pressure was unchanged throughout sleep stages during AutoSet titration . CPAP pressure selected with conventional or daytime manual titration ( 7.5(2.2 ) cm H2O and 7.4(1.5 ) cm H2O , ns ) were significantly lower ( P < 0.001 ) than with AutoSet ( 9.4(1.6 ) cm H20 . All groups showed similar decrease of sleepiness and hours of use of CPAP at 3 months of follow-up . Automatic and manual daytime PSG studies after sleep deprivation are useful for CPAP titration in unselected patients with SAHS . Pressure selected with AutoSet is significantly higher than with conventional daytime or nighttime titration , although not significant in terms of treatment compliance and symptom improvement Autoadjusting nasal continuous positive airway pressure ( CPAP ) greatly reduces the apnoea/hypopnoea index ( AHI ) , and affords a significant reduction in median pressure ( P50 ) compared-with manually titrated conventional nasal CPAP . The aim of the present study was to test whether these benefits were maintained in the medium term at home , in a double-blind crossover study . Ten sequential subjects ( mean AHI 52.9 x h(-1 ) ) were enrolled . After a manual titration , subjects were r and omly allocated to Output:	The evidence base for other interventions is smaller , and does not provide sufficient information to determine whether there are important differences between pressure modification strategies and fixed CPAP on machine usage outcomes , symptoms and quality of life . In adults with moderate to severe sleep apnoea starting positive airway pressure therapy , auto-CPAP probably increases machine usage by about 13 minutes per night . The effects on daytime sleepiness scores with auto-CPAP are not clinical ly meaningful . AHI values are slightly lower with fixed CPAP .
MS22126	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The effect of smoking on survival in cancer patients is limited by the lack of structured prospect i ve assessment s of smoking at diagnosis . To assess the effect of smoking at diagnosis on survival , structured smoking assessment s were obtained in a cohort of 5,185 cancer patients within 30 days of a cancer diagnosis between 1982 and 1998 . Hazard ratios ( HRs ) or odds ratios were generated to analyze the effects of smoking at diagnosis on overall mortality ( OM ) and disease‐specific mortality ( DSM ) in a patient cohort from 13 disease sites containing at least 100 patients in each disease site . With a minimum of 12 years of follow‐up , current smoking increased OM risk versus recent quit ( HR 1.17 ) , former ( HR 1.29 ) and never smokers ( HR 1.38 ) in the overall cohort . Current smoking increased DSM risk versus former ( HR 1.23 ) and never smokers ( HR 1.18 ) . In disease sites with proportionately large ( > 20 % ) recent quit cohorts ( lung and head/neck ) , current smoking increased OM and DSM risks as compared with recent quit . Current smoking increased mortality risks in lung , head/neck , prostate and leukemia in men and breast , ovary , uterus and melanoma in women . Current smoking was not associated with any survival benefit in any disease site . Data using prospect i ve structured smoking assessment s demonstrate that current smoking increased long‐term OM and DSM . St and ardized smoking assessment at diagnosis is an important variable for evaluating outcomes in cancer patients Background : It is increasingly recognised that host-related factors may be important in determining cancer outcome . The aim was to examine the relationship between patient physiology , the systemic inflammatory response and survival after colorectal cancer resection . Methods : Patients undergoing potentially curative resection of colorectal cancer were identified from a prospect ively maintained data base . Patient physiology was assessed using the physiological and operative severity score for the enumeration of mortality and morbidity ( POSSUM ) criteria . The systemic inflammatory response was assessed using the modified Glasgow Prognostic Score ( mGPS ) . Multivariate 5-year survival analysis was carried out with calculation of hazard ratios ( HR ) . Results : A total of 320 patients were included . During follow-up ( median 74 months ) , there were 136 deaths : 83 colorectal cancer related and 53 non-cancer related . Independent predictors of cancer-specific survival were age ( HR : 1.46 , P<0.01 ) , Dukes stage ( HR : 2.39 , P<0.001 ) , mGPS ( HR : 1.78 , P<0.001 ) and POSSUM physiology score ( HR : 1.38 , P=0.02 ) . Predictors of overall survival were age ( HR : 1.64 , P<0.001 ) , smoking ( HR : 1.52 , P=0.02 ) , Dukes stage ( HR : 1.64 , P<0.001 ) , mGPS ( HR : 1.60 , P<0.001 ) and POSSUM physiology score ( HR : 1.27 , P=0.03 ) . A relationship between mGPS and POSSUM physiology score was also established ( P<0.006 ) . Conclusion : The POSSUM physiology score and the systemic inflammatory response are strongly associated and both are independent predictors of cancer specific and overall survival in patients undergoing potentially curative resection of colorectal cancer BACKGROUND Cigarette smoking is an established risk factor for colorectal cancer . Because colorectal carcinogenesis is a heterogeneous process , we investigated whether cigarette smoking is differentially associated with molecularly defined subtypes of colorectal cancer . METHODS We evaluated associations between smoking and incident colorectal cancer , overall and by microsatellite instability ( MSI ) phenotype ( MSI-high vs MSI-low or microsatellite stable ) , CpG isl and methylator phenotype ( CIMP positive or CIMP negative ) , and BRAF mutation status ( BRAF mutation positive or BRAF mutation negative ) , among 37 399 participants in a population -based cohort study ( the Iowa Women 's Health Study ) . Cigarette smoking ( and other exposures ) was assessed by self-report at baseline in 1986 , including smoking status ( never and ever [ former or current ] ) , age at initiation , total duration , average number of cigarettes smoked per day , cumulative pack-years , and induction period . Vital status and state of residence were determined by mailed follow-up question naires in 1987 , 1989 , 1992 , and 1997 and by linkage to Iowa death certificate records . Nonrespondents were checked via the National Death Index to identify descendants . Participants with newly diagnosed ( ie , incident ) colorectal cancer were identified through annual linkage with the Iowa Cancer Registry . Archived paraffin-embedded tumor tissue specimens were obtained for 555 patients with colorectal cancer who were diagnosed from January 1 , 1986 , through December 31 , 2002 , and MSI status , CIMP status , and BRAF status were determined . Multivariable Cox regression models were fit to estimate relative risks ( RRs ) and 95 % confidence intervals ( CIs ) . RESULTS Ever-smokers were at moderately increased risk for incident colorectal cancer ( RR = 1.19 , 95 % CI = 1.05 to 1.35 ) compared with never-smokers . Higher risk estimates were observed for current smokers with MSI-high tumors ( RR = 1.99 , 95 % CI = 1.26 to 3.14 ) , CIMP-positive tumors ( RR = 1.88 , 95 % CI = 1.22 to 2.90 ) , and BRAF mutation-positive tumors ( RR = 1.92 , 95 % CI = 1.22 to 3.02 ) . Other smoking-related variables ( ie , age at initiation , total duration , average number of cigarettes smoked per day , cumulative pack-years , and induction period ) were also associated with MSI-high , CIMP-positive , and BRAF mutation-positive tumor subtypes . Conversely , cigarette smoking status ( ever vs never ) was not associated with the MSI-low or microsatellite stable ( RR = 1.00 , 95 % CI = 0.79 to 1.25 ) , CIMP-negative ( RR = 1.02 , 95 % CI = 0.81 to 1.30 ) , or BRAF mutation-negative subtypes ( RR = 1.00 , 95 % CI = 0.65 to 1.27 ) . CONCLUSIONS In this prospect i ve study of older women , cigarette smoking was associated with the MSI-high , CIMP-positive , and BRAF mutation-positive colorectal cancer subtypes , which indicates that epigenetic modification may be functionally involved in smoking-related colorectal carcinogenesis PURPOSE By using data from North Central Cancer Treatment Group Phase III Trial N0147 , a r and omized adjuvant trial of patients with stage III colon cancer , we assessed the relationship between smoking and cancer outcomes , disease-free survival ( DFS ) , and time to recurrence ( TTR ) , accounting for heterogeneity by patient and tumor characteristics . PATIENTS AND METHODS Before r and om assignment to infusional fluorouracil , leucovorin , and oxaliplatin ( FOLFOX ) or FOLFOX plus cetuximab , 1,968 participants completed a question naire on smoking history and other risk factors . Cox models assessed the association between smoking history and the primary trial outcome of DFS ( ie , time to recurrence or death ) , as well as TTR , adjusting for other clinical and patient factors . The median follow-up was 3.5 years among patients who did not experience events . RESULTS Compared with never-smokers , ever smokers experienced significantly shorter DFS ( 3-year DFS proportion : 70 % v 74 % ; hazard ratio [ HR ] , 1.21 ; 95 % CI , 1.02 to 1.42 ) . This association persisted after multivariate adjustment ( HR , 1.23 ; 95 % CI , 1.02 to 1.49 ) . There was significant interaction in this association by BRAF mutation status ( P = .03 ) : smoking was associated with shorter DFS in patients with BRAF wild-type ( HR , 1.36 ; 95 % CI , 1.11 to 1.66 ) but not BRAF mutated ( HR , 0.80 ; 95 % CI , 0.50 to 1.29 ) colon cancer . Smoking was more strongly associated with poorer DFS in those with KRAS mutated versus KRAS wild-type colon cancer ( HR , 1.50 [ 95 % CI , 1.12 to 2.00 ] v HR , 1.09 [ 95 % CI , 0.85 to 1.39 ] ) , although interaction by KRAS mutation status was not statistically significant ( P = .07 ) . Associations were comparable in analyses of TTR . CONCLUSION Overall , smoking was significantly associated with shorter DFS and TTR in patients with colon cancer . These adverse relationships were most evident in patients with BRAF wild-type or KRAS mutated colon cancer Output:	Our results support the existence of detrimental effects of smoking on survival also after CRC diagnosis .
MS22127	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: A prospect i ve , r and omized pilot study was undertaken to compare the efficacy of continuous versus intermittent ceftazidime in ICU patients with nosocomial pneumonia . Ceftazidime was administered either as a 3 g/day continuous infusion ( CI ) or an intermittent infusion ( II ) of 2 g every 8 h. In addition , all patients received concomitant once-daily tobramycin . The demographics of the evaluable patients ( n = 35 ) were similar between the groups : age ( years ) , CI 46 + /- 16 , II 56 + /- 20 ; Apache score , CI 14 + /- 4 , II 16 + /- 6 ; time ( days ) from admission to diagnosis , CI 9 + /- 6 , II 9 + /- 6 . Clinical efficacy , defined as cure/improvement was similar between groups [ n ( % ) , CI 16/17 ( 94 ) , II 15/18 ( 83 ) ] , while microbiological response was also comparable [ n ( % ) , CI 10/13 ( 76 ) , II 12/15 ( 80 ) ] . Minimal inhibitory concentrations ( MICs ) for all isolates were measured throughout the treatment course ; there was no development of resistance during therapy for either regimen . While limited clinical data exist , our results suggest that the use of ceftazidime by CI administration maintains clinical efficacy , optimizes the pharmacodynamic profile and uses less antibiotic compared with the st and ard 2 g every 8 h intermittent dosing regimen The extreme pharmacokinetic behaviour of drugs sometimes observed in critically ill patients poses a significant threat to the achievement of optimal antibiotic treatment outcomes . Scant information on beta-lactam antibiotic therapeutic drug monitoring ( TDM ) is available . The objective of this prospect i ve study was to evaluate the practicality and utility of a beta-lactam TDM programme in critically ill patients . TDM was performed twice weekly on all eligible patients at a 30-bed tertiary referral critical care unit . Blood concentrations were determined by fast-throughput high-performance liquid chromatography ( HPLC ) assays and were available within 12h of sampling . Dose adjustment was instituted if the trough or steady-state blood concentration was below 4 - 5x the minimum inhibitory concentration ( MIC ) or above 10x MIC . A total of 236 patients were subject to TDM over an 11-month period . The mean+/-st and ard deviation age was 53.5+/-18.3 years . Dose adjustment was required in 175 ( 74.2 % ) of the patients , with 119 of these patients ( 50.4 % ) requiring dose increases after the first TDM . For outcome of therapy , 206 ( 87.3 % ) courses result ed in a positive treatment outcome and there were 30 ( 12.7 % ) treatment failures observed including 14 deaths and 15 courses requiring escalation to broader-spectrum agents ; 1 course was ceased due to an adverse drug reaction . Using binomial logistic regression , only an elevated Acute Physiology and Chronic Health Evaluation ( APACHE ) II score ( P<0.01 ) and elevated plasma creatinine concentration ( P=0.05 ) were found to be predictive of mortality . In conclusion , further research is required to determine definitively whether achievement of optimal beta-lactam pharmacodynamic targets improves clinical outcomes Introduction Meropenem bactericidal activity depends on the time when the free drug concentrations remain above the minimum inhibitory concentration of pathogens . The goal of this study was to compare clinical and bacteriological efficacy of continuous meropenem infusion versus bolus administration in critically ill patients with severe infection , and to evaluate the safety of both dosing regimens . Methods Patients admitted to the interdisciplinary Intensive Care Unit ( ICU ) who suffered from severe infections and received meropenem were r and omized either in the Infusion group ( n = 120 ) or in the Bolus group ( n = 120 ) . Patients in the Infusion group received a loading dose of 2 g of meropenem followed by a continuous infusion of 4 g of meropenem over 24 hours . Patients in the Bolus group were given 2 g of meropenem over 30 minutes every 8 hours . Clinical and microbiological outcome , safety , meropenem-related length of ICU and hospital stay , meropenem-related length of mechanical ventilation , duration of meropenem treatment , total dose of meropenem , and ICU and in-hospital mortality were assessed . Results Clinical cure at the end of meropenem therapy was comparable between both groups ( 83.0 % patients in the Infusion vs. 75.0 % patients in the Bolus group ; P = 0.180 ) . Microbiological success rate was higher in the Infusion group as opposed to the Bolus group ( 90.6 % vs. 78.4 % ; P = 0.020 ) . Multivariate logistic regression identified continuous administration of meropenem as an independent predictor of microbiological success ( OR = 2.977 ; 95 % CI = 1.050 to 8.443 ; P = 0.040 ) . Meropenem-related ICU stay was shorter in the Infusion group compared to the Bolus group ( 10 ( 7 to 14 ) days vs. 12 ( 7 to 19 ) days ; P = 0.044 ) as well as shorter duration of meropenem therapy ( 7 ( 6 to 8) days vs. 8 ( 7 to 10 ) days ; P = 0.035 ) and lower total dose of meropenem ( 24 ( 21 to 32 ) grams vs. 48 ( 42 to 60 ) grams ; P < 0.0001 ) . No severe adverse events related to meropenem administration in either group were observed . Conclusions Continuous infusion of meropenem is safe and , in comparison with higher intermittent dosage , provides equal clinical outcome , generates superior bacteriological efficacy and offers encouraging alternative of antimicrobial therapy in critically ill patients See related commentary by De Waele and Carlier , http://ccforum.com/content/17/2/130 Introduction Improved methods to optimize drug dosing in the critically ill are urgently needed . Traditional prescribing culture involves recognition of factors that m and ate dose reduction ( such as renal impairment ) , although optimizing drug exposure , through more frequent or augmented dosing , represents an evolving strategy . Elevated creatinine clearance ( CLCR ) has been associated with sub-therapeutic antibacterial concentrations in the critically ill , a concept termed augmented renal clearance ( ARC ) . We aim ed to determine the prevalence of ARC in a cohort of septic and traumatized critically ill patients , while also examining demographic , physiological and illness severity characteristics that may help identify this phenomenon . Methods This prospect i ve observational study was performed in a 30-bed tertiary level , university affiliated , adult intensive care unit . Consecutive traumatized and septic critically ill patients , receiving antibacterial therapy , with a plasma creatinine concentration ≤110 μmol/L , were eligible for enrolment . Pulse contour analysis ( Vigileo / Flo Trac ® system , Edwards Lifesciences , Irvine , CA , USA ) , was used to provide continuous cardiac index ( CI ) assessment over a single six-hour dosing interval . Urinary CLCR measures were obtained concurrently . Results Seventy-one patients contributed data ( sepsis n = 43 , multi-trauma n = 28 ) . Overall , 57.7 % of the cohort manifested ARC , although there was a greater prevalence in trauma ( 85.7 % versus 39.5 % , P < 0.001 ) . In all patients , a weak correlation was noted between CI and CLCR ( r = 0.346 , P = 0.003 ) . This was mostly driven by septic patients ( r = 0.508 , P = 0.001 ) , as no correlation ( r = -0.012 , P = 0.951 ) was identified in trauma . Those manifesting ARC were younger ( P<0.001 ) , male ( P = 0.012 ) , with lower acute physiology and chronic health evaluation ( APACHE ) II ( P= 0.008 ) and modified sequential organ failure assessment ( SOFA ) scores ( P = 0.013 ) , and higher cardiac indices ( P = 0.013 ) . In multivariate analysis , age ≤50 years , trauma , and a modified SOFA score ≤4 , were identified as significant risk factors . These had greater utility in predicting ARC , compared with CI assessment alone . Conclusions Diagnosis , illness severity and age , are likely to significantly influence renal drug elimination in the critically ill , and must be regularly considered in future study design and daily prescribing practice BACKGROUND Beta-lactam antibiotics are a commonly used treatment for severe sepsis , with intermittent bolus dosing st and ard therapy , despite a strong theoretical rationale for continuous administration . The aim of this trial was to determine the clinical and pharmacokinetic differences between continuous and intermittent dosing in patients with severe sepsis . METHODS This was a prospect i ve , double-blind , r and omized controlled trial of continuous infusion versus intermittent bolus dosing of piperacillin-tazobactam , meropenem , and ticarcillin-clavulanate conducted in 5 intensive care units across Australia and Hong Kong . The primary pharmacokinetic outcome on treatment analysis was plasma antibiotic concentration above the minimum inhibitory concentration ( MIC ) on days 3 and 4 . The assessed clinical outcomes were clinical response 7 - 14 days after study drug cessation , ICU-free days at day 28 and hospital survival . RESULTS Sixty patients were enrolled with 30 patients each allocated to the intervention and control groups . Plasma antibiotic concentrations exceeded the MIC in 82 % of patients ( 18 of 22 ) in the continuous arm versus 29 % ( 6 of 21 ) in the intermittent arm ( P = .001 ) . Clinical cure was higher in the continuous group ( 70 % vs 43 % ; P = .037 ) , but ICU-free days ( 19.5 vs 17 days ; P = .14 ) did not significantly differ between groups . Survival to hospital discharge was 90 % in the continuous group versus 80 % in the intermittent group ( P = .47 ) . CONCLUSIONS Continuous administration of beta-lactam antibiotics achieved higher plasma antibiotic concentrations than intermittent administration with improvement in clinical cure . This study provides a strong rationale for further multicenter trials with sufficient power to identify differences in patient-centered endpoints The st and ard mode of administration of piperacillin treatment is by intermittent infusion . However , continuous infusion may be advantageous as beta-lactam antibiotics exhibit time-dependent antibacterial activity . In previous studies , we found a higher rate of clinical cure of ventilator-associated pneumonia ( VAP ) by continuous infusion rather than intermittent infusion of meropenem and ceftazidime . Therefore , the objective of this historical cohort study was to establish the clinical efficacy of piperacillin/tazobactam ( PIP/TAZ ) administered by continuous and intermittent infusion in the treatment of VAP in patients without renal failure . Logistic regression analysis showed a higher probability of clinical cure of VAP by continuous compared with intermittent infusion when the microorganism responsible for VAP had a minimum inhibitory concentration ( MIC ) of 8 microg/mL [ 8/9 ( 88.9 % ) vs. 6/15 ( 40.0 % ) ; odds ratio (OR)=10.79 , 95 % confidence interval ( CI ) 1.01 - 588.24 ; P=0.049 ] or 16 microg/mL [ 7/8 ( 87.5 % ) vs. 1/6 ( 16.7 % ) ; OR=22.89 , 95 % CI 1.19 - 1880.78 ; P=0.03 ] . Thus , administration of PIP/TAZ by continuous infusion may be considered more effective than intermittent infusion for the treatment of VAP caused by Gram-negative bacteria when the MIC of the microorganism responsible for VAP is 8 - 16 microg/mL in patients without renal failure Augmented renal clearance ( ARC ) is known to influence β-lactam antibiotic pharmacokinetics . This sub study of the BLING-II trial aim ed to explore the association between ARC and patient outcomes in a large r and omised clinical trial . BLING-II enrolled 432 participants with severe sepsis r and omised to receive β-lactam therapy by continuous or intermittent infusion . An 8-h creatinine clearance ( CLCr ) measured on Day 1 was used to identify ARC , defined as CLCr ≥ 130 mL/min . Patients receiving any form of renal replacement therapy were excluded . Primary outcome was alive ICU-free days at Day 28 . Secondary outcomes included 90-day mortality and clinical cure at 14 days following antibiotic cessation . A total of 254 patients were included , among which 45 ( 17.7 % ) manifested ARC [ median ( IQR ) CLCr 165 ( 144 - 198 ) mL/min ] . ARC patients were younger ( P < 0.001 ) , more commonly male ( P Output:	Conclusions CI of beta-lactam antibiotics is associated with better cure rates and higher % fT > MIC when administered to critically ill patients with respiratory infections , but may be most beneficial in severely ill patients with more resistant Gram-negative bacterial infections
MS22128	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objectives : To present the prevalence of self reported musculoskeletal diseases , the coexistence of these diseases , the test-retest reliability with six months in between , and the association with musculoskeletal pain symptoms . Methods : Twelve layman descriptions of common musculoskeletal diseases were part of the question naires of a prospect i ve cohort study of a r and om sample in the general Dutch population aged 25 years or more ( baseline : n=3664 , follow up after six months : n=2338 ) . Data collection also included information about pain relating to five different anatomical areas . Results : Osteoarthritis of the knee ( men 10.1 % , women 13.6 % ) was amongst the most reported musculoskeletal diseases , whereas the figures for self reported rheumatoid arthritis ( RA ) were 1.6 % and 4.6 % for men and women , respectively . The coexistence of these diseases is high : 47 of the 66 combinations were reported more often than would be expected if they were independent of each other ( p<0.05 ) . For most diseases the test-retest reliability was good ( κ between 0.6 and 0.8 ) , but for repetitive strain injury ( κ=0.37 ) and chronic arthritis other than RA ( κ=0.44 ) the agreement was fair to moderate . All complaints of pain were more often reported by those with musculoskeletal diseases than those without those diseases , and the pain pattern was disease-specific . Conclusions : Self reported musculoskeletal diseases are highly prevalent , with a fair to good reliability and a disease-specific pain pattern . Health surveys are a limited but valuable source of information for this group of health problems , which is not available from most other sources of information OBJECTIVE The present study aim ed to evaluate the effects of Pilates exercise program on pain , functional status and quality of life in women with postmenopausal osteoporosis . DESIGN The study was performed as a r and omized , prospect i ve , controlled and single-blind trial . PARTICIPATIONS : Seventy women ( age range , 45 - 65 years ) with the diagnosis of postmenopausal osteoporosis were included . METHODS AND INTERVENTIONS Patients were r and omly allocated into two groups ( home and Pilates exercise groups ) . Patients in the Pilates exercise group underwent a supervised Pilates exercise program twice a week for one year . Patients in the home exercise group were asked to perform a home exercise program consisting of thoracic extension exercises . Patients were evaluated at baseline and after one year of participation in the exercise programs . MAIN OUTCOME MEASUREMENTS Visual Analog Scale for pain , six-minute walking and sit-to-st and tests for functional status , and the Qualeffo-41 Question naire and the Short Form-36 ( SF-36 ) for quality of life . Patients were also asked to report the number of falls during the intervention . RESULTS At the end of the study , the results of 60 patients were analyzed . A significant improvement was noted in all evaluation parameters at the end of the exercise program in the Pilates exercise group . Except for Qualeffo- Leisure Time Activities , SF-36 physical role limitation and emotional role limitation subscales , a significant improvement was noted in all other evaluation parameters at the end of the exercise program in the home exercise group . Improvement was significantly greater in the Pilates exercise group compared to the home exercise group in all parameters . CONCLUSION Pilates exercises may be a safe and an effective treatment alternative for the quality of life in patients with postmenopausal osteoporosis Background Chronic low back pain is an expensive and difficult condition to treat . One of the interventions widely used by physiotherapists in the treatment of chronic non-specific low back pain is exercise therapy based upon the Pilates principles . Pilates exercises can be performed with or without specific equipment . These two types of Pilates exercises have never been compared on a high- quality r and omised controlled trial . Methods / design This r and omised controlled trial with a blinded assessor will evaluate eighty six patients of both genders with chronic low back pain , aged between 18 and 60 years , from one Brazilian private physiotherapy clinic . The patients will be r and omly allocated into two groups : Mat Group will perform the exercises on the ground while the Equipment-based Group will perform the Pilates method exercises on the following equipment : Cadillac , Reformer , Ladder Barrel , and Step Chair . The general and specific disability of the patient , kinesiophobia , pain intensity and global perceived effect will be evaluated by a blinded assessor before r and omisation and at six weeks and six months after r and omisation . In addition , the expectation of the participants and their confidence with the treatment will be evaluated before r and omisation and after the first treatment session , respectively . Discussion This will be the first study aim ing to compare the effectiveness of Mat and Equipment-based Pilates exercises in patients with chronic non-specific low back pain . The results may help health-care professionals in clinical decision-making and could potentially reduce the treatment costs of this condition . Trial registration Brazilian Registry of Clinical Trials UNLABELLED Altan L , Korkmaz N , Bingol U , Gunay B. Effect of Pilates training on people with fibromyalgia syndrome : a pilot study . OBJECTIVE To investigate the effects of Pilates on pain , functional status , and quality of life in fibromyalgia , which is known to be a chronic musculoskeletal disorder . DESIGN R and omized , prospect i ve , controlled , and single-blind trial . SETTING Physical medicine and rehabilitation department . PARTICIPANTS Women ( N=50 ) who had a diagnosis of fibromyalgia syndrome ( FMS ) according to the American College of Rheumatology criteria . INTERVENTION The participants were r and omly assigned into 2 groups . In group 1 , a Pilates exercise program of 1 hour was given by a certified trainer to 25 participants 3 times a week for 12 weeks . In group 2 , which was design ed as the control group , 25 participants were given a home exercise ( relaxation/stretching ) program . In both groups , pre- ( week 0 ) and posttreatment ( week 12 and week 24 ) evaluation was performed by one of the authors , who was blind to the group allocation . MAIN OUTCOME MEASURES Primary outcome measures were pain ( visual analog scale ) and Fibromyalgia Impact Question naire ( FIQ ) . Exploratory outcome measures were number of tender points , algometric score , chair test , and Nottingham Health Profile . RESULTS Twenty-five Pilates exercise and 24 relaxation/stretching exercise participants completed the study . In group 1 , significant improvement was observed in both pain and FIQ at week 12 but only in FIQ at 24 weeks . In group 2 , no significant improvement was obtained in pain and FIQ at week 12 and week 24 . Comparison of the 2 groups showed significantly superior improvement in pain and FIQ in group 1 at week 12 but no difference between the 2 groups at week 24 . CONCLUSIONS We suggest Pilates as an effective and safe method for people with FMS . Our study is the first clinical study design ed to investigate the role of the Pilates method in FMS treatment . We believe that further research with more participants and longer follow-up periods could help assess the therapeutic value of this popular physical exercise method [ Purpose ] The purpose of this study was to examine the influence of mat Pilates and apparatus Pilates on pain and static balance of businesswomen with chronic back pain . [ Subjects and Methods ] Participants were r and omly allocated to Pilates mat exercises ( PME ) or Pilates apparatus exercise ( PAE ) , and performed the appropriate Pilates exercises 3 days per week for 8 weeks . In order to measure the improvement in the participants ’ static balance ability as a result of the exercise , the sway length and sway velocity of the subjects were measured before and after the experiment while the subjects stood on a Balance Performance Monitor ( BPM ) facing the front wall for 30 seconds with their eyes open . The visual analogue scale ( VAS ) was used to measure the degree of pain . [ Results ] The VAS score , sway length , and sway velocity of both groups decreased significantly after the experiment , but the PME group showed a greater decrease than the PAE group . [ Conclusion ] PME showed greater improvement in pain level and balance compared with PAE in this research . Since the subjects of this study were patients with low back pain , PME is assumed to have been more suitable and effective because it uses body weight to strengthen core muscles rather than heavier apparatuses as in PAE PURPOSE This single-assessor-blinded r and omized controlled trial aim ed to compare the efficacy of physiotherapy-delivered clinical Pilates and general exercise for chronic low back pain . METHODS Eighty-seven community volunteers with low back pain for ≥3 months and age 18 - 70 were r and omized to either the Pilates ( n = 44 ) or general exercise ( n = 43 ) group . The primary outcome was pain/disability measured with the Quebec scale . Secondary outcomes included pain on a numeric rating scale , Patient-Specific Functional Scale , Pain Self-efficacy Question naire , quality of life , and global perceived effect of treatment . All participants attended 60-min exercise sessions twice weekly for 6 wk supervised by a physiotherapist and performed daily home exercises that were continued during the follow-up . Participants from the clinical Pilates group received an individualized direction-specific exercise program prescribed by the physiotherapist after a clinical examination . The general exercise group received a generic set of exercises that were multidirectional and nonspecific . Outcomes were assessed after 6 wk ( primary time point ) and at 12 and 24 wk . Differences in mean change were compared between groups using ANCOVA adjusted for baseline values of the outcome . RESULTS Eighty-three participants ( 96 % ) completed the 6-wk intervention and 60 ( 69 % ) completed the 24-wk follow-up . At 6 wk , no difference was found between groups for change in the Quebec scale ( 3.5 , 95 % confidence interval = -7.3 to 0.3 , P = 0.07 ) ; both groups showed significant improvements . Similar results were found at the 12- and 24-wk follow-up and for the secondary outcome measures . CONCLUSIONS An individualized clinical Pilates program produced similar beneficial effects on self-reported disability , pain , function and health-related quality of life as a general exercise program in community volunteers with chronic low back pain Study Design . R and omized controlled trial . Objective . This is the companion study to a previous publication that presented 8-week pain , disability , and trunk muscle motor control results . The objective of this study was to compare the effect of 8 weeks of specific trunk exercises and stationary cycling on outcomes measures of catastrophizing and fear-avoidance beliefs ( FAB ) in patients with chronic nonspecific low back pain , and provide 6-month outcome data for all self-report measures . Summary of Background Data . It is thought that any form of moderate-to-vigorous physical activity is sufficient to address catastrophizing and FAB , and concomitant levels of pain and disability . Methods . Sixty-four patients with low back pain were r and omly assigned to 8 weeks of specific trunk exercise group ( SEG ) , or stationary cycling group ( CEG ) . Self-rated pain , disability , catastrophizing and FAB scores were collected before , immediately after ( 8 wk ) , and 6 months after the training program . Clinical ly meaningful improvements were defined as greater than a 30 % reduction from baseline in pain and disability scores . “ Intention-to-treat ” principles were used for missing data . Per- protocol analysis was performed on participants who attended at least two-thirds of the exercise sessions . Results . At 8 weeks , disability was significantly lower in the SEG compared with the CEG ( d = 0.62 , P = 0.018 ) . Pain was reduced from baseline in both the groups after training ( P < 0.05 ) , but was lower for the SEG ( P < 0.05 ) . FAB scores were reduced in the SEG at 8 weeks , and in the CEG at 6 months . No between-group differences in FAB scores were observed . Similar reductions in catastrophizing in each group were observed at each time point . At 6 months , the overall data pattern suggested no long-term difference between groups . Per- protocol analysis of clinical ly meaningful improvements suggests no between-group differences for how many patients are likely to report improvement . Conclusion . Inferential statistics suggest greater improvements at 8 weeks , but not 6 months , for the SEG . Inspection of clinical ly meaningful changes based on a minimum level of adherence suggests no between-group differences . If a patient with low back pain adheres to either specific trunk exercises or stationary cycling , it is reasonable to think that similar improvements will be achieved . Level of Evidence : OBJECTIVE To evaluate the influence of pain on vertical ground-reaction force ( VGRF ) in patients with low back problems and the effect of the Pilates method on the gait of these patients . DESIGN A single-blind r and omized controlled trial . PARTICIPANTS 28 individuals assigned to a control group ( n = 11 ) and a low-back group ( n = 17 ) , the latter of which was subdivided into a Pilates group ( n = 8) and a no-Pilates group ( n = 9 ) . INTERVENTION The Pilates group undertook 15 sessions of Pilates . MAIN OUTCOME MEASURES The VGRF parameters were recorded during preferred and faster walking speeds . The data were collected before and after the intervention . RESULTS The weight-acceptance rate and push-off rate were significantly less in the right lower limb of low-back group than of the control group at preferred speed . Improvements were seen in the Pilates group postintervention , with increased middle-support force for the left lower limb at faster walking speed and decreased pain ; this did not occur in the no-Pilates group . CONCLUSIONS These results suggest that patients with low back pain use strategies to attenuate the amount of force imposed on their body . The Pilates method can improve weight Output:	The items were stratified as follows : Pilates method versus other kind of exercises ( n = 6 trials ) and Pilates method versus no treatment group or minimal intervention for short-term pain ( n = 9 trials ) ; the therapeutic effect of the Pilates method in r and omized cohorts ( n = 5 ) ; and analysis of review s ( n = 9).We found that there is a dearth of studies that clearly demonstrates the efficacy of a specific Pilates exercise program over another in the treatment of chronic pain . However , the consensus in the field suggests that Pilates method is more effective than minimal physical exercise intervention in reducing pain .
MS22129	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: A group of 200 patients who presented in general practice with symptoms but no abnormal physical signs and in whom no definite diagnosis was made were r and omly selected for one of four consultations : a consultation conducted in a " positive manner , " with and without treatment , and a consultation conducted in a " non-positive manner , " called a negative consultation , with and without treatment . Two weeks after consultation there was a significant difference in patient satisfaction between the positive and negative groups but not between the treated and untreated groups . Similarly , 64 % of those receiving a positive consultation got better , compared with 39 % of those who received a negative consultation ( p = 0.001 ) and 53 % of those treated got better compared with 50 % of those not treated ( p = 0.5 ) Summary The efficacy of naproxen and paracetamol in relieving uterine cramps has been compared in a sequential trial . The treatments did not differ significantly in a two-sided test in 56 patients . A corresponding fixed sample test would have required 140 patients to obtain the same significance level and power . In addition to uterine pain , the effect on episiotomy pain was also estimated at the termination of the trial . Again , there seemed to be no difference between naproxen and paracetamol BACKGROUND For many years it has been cl aim ed that observational studies find stronger treatment effects than r and omized , controlled trials . We compared the results of observational studies with those of r and omized , controlled trials . METHODS We search ed the Abridged Index Medicus and Cochrane data bases to identify observational studies reported between 1985 and 1998 that compared two or more treatments or interventions for the same condition . We then search ed the Medline and Cochrane data bases to identify all the r and omized , controlled trials and observational studies comparing the same treatments for these conditions . For each treatment , the magnitudes of the effects in the various observational studies were combined by the Mantel-Haenszel or weighted analysis -of-variance procedure and then compared with the combined magnitude of the effects in the r and omized , controlled trials that evaluated the same treatment . RESULTS There were 136 reports about 19 diverse treatments , such as calcium-channel-blocker therapy for coronary artery disease , appendectomy , and interventions for subfertility . In most cases , the estimates of the treatment effects from observational studies and r and omized , controlled trials were similar . In only 2 of the 19 analyses of treatment effects did the combined magnitude of the effect in observational studies lie outside the 95 percent confidence interval for the combined magnitude in the r and omized , controlled trials . CONCLUSIONS We found little evidence that estimates of treatment effects in observational studies reported after 1984 are either consistently larger than or qualitatively different from those obtained in r and omized , controlled trials Patients who agree and those who refuse clinical trial entry may differ in attitudes towards decision control and the benefits associated with the trial arms . These differences , if they exist , have implication s for the process of obtaining informed consent and for the generalization of the results of a clinical trial . This paper describes the development and initial application of methods design ed to detect such differences . Developmental work involved creating an inventory of instruments design ed to determine patients ' attitudes towards participating in treatment decision making , permitting r and om selection of treatment , and undertaking the risks and benefits associated with the various treatments in a trial . Initial application involved modifying these instruments in terms of an actual chemotherapeutic trial for colonic adenocarcinoma , seeking responses to these measures from 60 non-eligible colorectal cancer patients , then determining whether those who would agree to trial entry differed systematic ally on these measures from those who indicated that they would refuse such a trial . Twenty-five of the respondents reported that , if faced with the actual decision , they would agree to trial entry : 35 would refuse . Refusers dem and ed more participation in decision making ( Chi-square ; P = 0.01 ) and a greater increment in treatment benefit ( t-test ; P = 0.0001 ) . Twenty-two of the 35 refusers reported aversion to r and omization as their primary reason for trial refusal . Since their particular content can be modified , these measures may be applicable to all clinical trials . They could be used to study the reasons patients accept or refuse trial entry and to determine if agreer-refuser attitude differences undermine the generalizability of a trials results To examine whether written informed consent might influence the results of clinical trials the effect of placebo when given with or without informed consent to patients suffering from insomnia was studied . The study was a single blind observer blinded trial , and patients were paired according to sex , age , and hospital environment . R and omisation assigned the first patient of each pair to the control group ( without informed consent ) or the group to give informed consent . Of the 56 patients , 26 refused to give informed consent , and the age and sex distribution of these differed significantly ( p less than 0.02 ) from the 30 pairs of patients ultimately enrolled into the study . In this " biased " sample , the hypnotic activity of placebo was significantly higher in the control group ( p less than 0.05 ) . It is concluded that the informed consent procedure biases the results of clinical trials and might affect their general applicability Background Despite the increasing dem and for acupuncture and homoeopathy in Germany , little is known about the effects of these treatments in routine care . We set up a pragmatic documentation study in general practice funded within the scope of project launched by a German health insurer . Patients were followed-up for up to four years . Methods The aim of the project was to study the effects and benefits of acupuncture and /or homoeopathy , and to assess patient satisfaction within a prospect i ve documentation of over 5000 acupuncture and over 900 homoeopathy patients . As data sources , we used the documentation made available by therapists on every individual visit and a st and ardised quality -of-life question naire ( MOS SF-36 ) ; these were complemented by questions concerning the patient 's medical history and by questions on patient satisfaction . The health insurer provided us with data on work absenteeism . Results Descriptive analyses of the main outcomes showed benefit of treatment with middle to large-sized effects for the quality of life question naire SF-36 and about 1 point improvement on a rating scale of effects , given by doctors . Data on the treatment and the patients ' and physicians ' background suggests chronically ill patients treated by fairly regular schemes . ConclusionS ince the results showed evidence of a subjective benefit for patients from acupuncture and homoeopathy , this may account for the increase in dem and for these treatments especially when patients are chronically ill and unsatisfied with the conventional treatment given previously QUESTIONS UNDER STUDY To date most of the published studies on the effectiveness of complementary therapies in cancer patients have yielded controversial results because of question able methodology . Research strategies and method ologies acceptable to both conventional and unconventional medicine are difficult to find due to different belief systems . In this publication we describe the development and implementation of a project conducted as part of National Research Programme 34 ( NFP 34 ) . Detailed analysis of our experiences might provide some information on how to deal with practical difficulties in the planning and conduct of further research projects in this field . The project involved the anthroposophical Lukas Clinic in Arlesheim and the Institute of Medical Oncology of the University Hospital , Berne . This interdisciplinary research project was devised to study the relative merits of these two schools of medicine in the care of advanced cancer patients . The project was made up of three components : ( 1 ) a registration study aim ed at comparing the case mix at the two institutions ; ( 2 ) a three armed r and omised study on the effectiveness of supportive therapy , comparing anthroposophy to psychosocial group therapy , and ( 3 ) a longitudinal study to monitor the evaluation of quality of life of patients at the anthroposophical clinic . METHODS After a brief review of the study protocol , which presents the theoretical framework of the project , problems of its implementation are described . Aspects of accrual , acceptance of r and omisation and data availability are presented using simple descriptive statistics and logistic regression . RESULTS The registration study was duly completed with a total of 567 patients . For several reasons ( not meeting inclusion requirements , high refusal rate ) the accrual into the r and omised study was slower than expected and required modification of the original design specifications with regard to inclusion criteria and data collection schedule . Additionally , a high dropout rate contributed to premature closure of this part of the project . The longitudinal study also suffered from low data availability at follow up . CONCLUSIONS The study protocol constituted a major effort at compromise without loss of scientific rigour , and this effort demonstrates that it is possible to allow for different views on patients , on clinical interventions and on research strategies when establishing collaboration between different schools of medicine . Despite a theoretically sound framework , the r and omised part of the project proved difficult in its practical execution . Some unexpected logistical constraints and some unmet expectations influenced the feasibility of this part of the project . Therefore , careful planning of research projects in this field of medicine should always include an extended analysis of various practical aspects of study implementation BACKGROUND Our aim was to assess the efficacy of a part-st and ardised verum acupuncture procedure , in accordance with the rules of traditional Chinese medicine , compared with that of part-st and ardised sham acupuncture and st and ard migraine prophylaxis with beta blockers , calcium-channel blockers , or antiepileptic drugs in the reduction of migraine days 26 weeks after the start of treatment . METHODS This study was a prospect i ve , r and omised , multicentre , double-blind , parallel-group , controlled , clinical trial , undertaken between April 2002 and July 2005 . Patients who had two to six migraine attacks per month were r and omly assigned verum acupuncture ( n=313 ) , sham acupuncture ( n=339 ) , or st and ard therapy ( n=308 ) . Patients received ten sessions of acupuncture treatment in 6 weeks or continuous prophylaxis with drugs . Primary outcome was the difference in migraine days between 4 weeks before r and omisation and weeks 23 - 26 after r and omisation . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N52683557 . FINDINGS Of 1295 patients screened , 960 were r and omly assigned to a treatment group . Immediately after r and omisation , 125 patients ( 106 from the st and ard group ) withdrew their consent to study participation . 794 patients were analysed in the intention-to-treat popoulation and 443 in the per- protocol population . The primary outcome showed a mean reduction of 2 .3 days ( 95 % CI 1.9 - 2.7 ) in the verum acupuncture group , 1.5 days ( 1.1 - 2.0 ) in the sham acupuncture group , and 2.1 days ( 1.5 - 2.7 ) in the st and ard therapy group . These differences were statistically significant compared with baseline ( p<0.0001 ) , but not across the treatment groups ( p=0.09 ) . The proportion of responders , defined as patients with a reduction of migraine days by at least 50 % , 26 weeks after r and omisation , was 47 % in the verum group , 39 % in the sham acupuncture group , and 40 % in the st and ard group ( p=0.133 ) . INTERPRETATION Treatment outcomes for migraine do not differ between patients treated with sham acupuncture , verum acupuncture , or st and ard therapy BACKGROUND Because the value of popular forms of alternative care for chronic back pain remains uncertain , we compared the effectiveness of acupuncture , therapeutic massage , and self-care education for persistent back pain . METHODS We r and omized 262 patients aged 20 to 70 years who had persistent back pain to receive Traditional Chinese Medical acupuncture ( n = 94 ) , therapeutic massage ( n = 78 ) , or self-care educational material s ( n = 90 ) . Up to 10 massage or acupuncture visits were permitted over 10 weeks . Symptoms ( 0 - 10 scale ) and dysfunction ( 0 - 23 scale ) were assessed by telephone interviewers masked to treatment group . Follow-up was available for 95 % of patients after 4 , 10 , and 52 weeks , and none withdrew for adverse effects . RESULTS Treatment groups were compared after adjustment for prer and omization covariates using an intent-to-treat analysis . At 10 weeks , massage was superior to self-care on the symptom scale ( 3.41 vs 4.71 , respectively ; P = .01 ) and the disability scale ( 5.88 vs 8.92 , respectively ; P<.001 ) . Massage was also superior to acupuncture on the disability scale ( 5.89 vs 8.25 , respectively ; P = .01 ) . After 1 year , massage was not better than self-care but was better than acupuncture ( symptom scale : 3.08 vs 4.74 , respectively ; P = .002 ; dysfunction scale : 6.29 vs 8.21 , respectively ; P = .05 ) . The massage group used the least medications ( P<.05 ) and had the lowest costs of subsequent care . CONCLUSIONS Therapeutic massage was effective for persistent low back pain , apparently providing long-lasting benefits . Traditional Chinese Medical acupuncture was relatively ineffective . Massage might be an effective alternative to conventional medical care for persistent back pain Background : Distant healing as a treatment modality is frequently used by patients and healers . Some preliminary evidence suggests possible effects . Since patients suffering from multiple chemical sensitivity and chronic fatigue syndrome have only few effective treatment options , distant healing will be offered as a treatment within a formal trial of distant healing . Design and Method : A four-armed r and omized trial will include 400 patients with self-attributed , environmental problems who fulfil the diagnostic criteria of severe idiopathic chronic fatigue , Output:	Evidence from RCTs forms the basis of meta-analyses and systematic review s. This hierarchy , founded on a pharmacological model of therapy , is generalized to other interventions which may be complex and non-pharmacological ( healing , acupuncture and surgery ) . Discussion The hierarchical model is valid for limited questions of efficacy , for instance for regulatory purpose s and newly devised products and pharmacological preparations . It is inadequate for the evaluation of complex interventions such as physiotherapy , surgery and complementary and alternative medicine ( CAM ) .
MS22130	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Ageing is associated with a decrease in physical activity . This decrease particularly occurs during specific transitional life stages . Especially during adolescence and young adulthood a steep decrease in physical activity is observed . Inactive people are often not aware of their inactivity . Providing feedback on the actual physical activity level by an activity monitor can increase awareness and may in combination with an individually tailored physical activity advice stimulate a physically active lifestyle . Methods In a r and omized controlled trial the effectiveness of providing an activity monitor in combination with a personal physical activity advice through the Internet will be examined . Outcome measures are level of physical activity , determinants of physical activity , quality of life , empowerment , aerobic fitness and body composition . Participants are relatively inactive adolescents and young adults who are measured at baseline , after 3 months intervention and 5 months after the end of the intervention . In addition , facilitating and hindering factors for implementation of the intervention will be investigated . Discussion The use of a personal activity monitor in combination with web-based assisted individually tailored health promotion offers a good opportunity to work interactively with large groups of adolescents and young adults and provide them with advice based on their actual activity level . It has great potential to motivate people to change their behaviour and to our knowledge has not been evaluated before A r and omised control trial evaluated the effectiveness of a theory-based persuasive leaflet design ed to encourage students to undertake at least one additional physical exercise session a week . Participants were 503 secondary school students attending a school in South-East Engl and . The leaflet was written to target potentially modifiable cognitive antecedents of exercise specified by the Theory of Planned Behaviour . It was separately augmented with two cognitive change techniques , result ing in three intervention conditions , leaflet alone ; leaflet plus motivational quiz , and leaflet plus implementation intention prompt , as well as a no-leaflet control condition . Cognitions and behaviour were measured immediately before and 3 weeks after intervention . The results showed that all three-leaflet interventions significantly increased reported exercise , intention to exercise and related cognitions , compared to the control condition , but did not differ in their impact . Mediation analysis showed that intervention effects on exercise were partially mediated by intentions and perceived behavioural control PURPOSE The present study investigates the effect of the Activ-O-Meter , an internet-based computer-tailored physical activity intervention in adolescents in six European centers involved in the HELENA study . METHODS Adolescents ( 12 - 17 years old ) from Vienna , Ghent , Heraklion , Dortmund , Athens , and Stockholm were r and omized into intervention and control schools . Participants in the intervention condition received the computer-tailored advice at baseline and after 1 month . Participants in the control condition received a generic st and ard advice . Effects were evaluated after 1 ( n = 675 ) and 3 months ( n = 494 ) using multi-level modeling . Physical activity levels were measured using the International Physical Activity Question naire for adolescents ( IPAQ-A ) . RESULTS After 1 month , the intervention group reported higher levels of moderate ( beta = -32.8 , 95 % CI ( confidence interval ) : -64.2 to -1.4 ) and vigorous ( beta = -28.0 , 95 % CI : -50.7 to -5.3 ) physical activity in leisure time , as well as higher levels of cycling for transport ( beta = -19.1 , 95 % CI : -34.4 to -7.6 ) compared to the control group . After 3 months , when the intervention group had received the tailored feedback twice , intervention effects were even stronger . Favorable changes in physical activity levels of all intensities and in different context s were found in the tailored group compared to the control group . Among adolescents not reaching the physical activity recommendations at baseline similar effects as in the total sample were found . CONCLUSIONS The data indicated that the computer-tailored physical activity intervention had positive effects on physical activity levels among the adolescents . However , the implementation of the computer-tailored intervention in the schools was not feasible in all countries OBJECTIVE To determine whether a multicomponent health promotion intervention for Dutch adolescents ( defined as persons between 12 and 14 years of age ) would be successful in influencing body composition and dietary and physical activity behavior in both the short and long terms . DESIGN R and omized controlled trial . SETTING Ten intervention and 8 control prevocational secondary schools . PARTICIPANTS A total of 1108 adolescents ( mean age , 12.7 years ) . Intervention An interdisciplinary program with an adapted curriculum for 11 lessons in biology and physical education and environmental change options . MAIN OUTCOME MEASURES Body height and weight , waist circumference , 4 skinfold thickness measurements , and dietary and physical activity behavior data . RESULTS Multilevel analyses showed that the intervention remained effective in preventing unfavorable increases in important measures of body composition after 20-month follow-up in girls ( biceps skinfold and sum of 4 skinfolds ) and boys ( triceps , biceps , and subscapular skinfolds ) . Consumption of sugar-containing beverages was significantly lower in intervention schools both after intervention ( boys : -287 mL/d ; 95 % confidence interval [ CI ] , -527 to -47 ; girls : -249 ; -400 to -98 ) and at 12-month follow-up ( boys : -233 ; -371 to -95 ; girls : -271 ; -390 to -153 ) . For boys , screen-viewing behavior was significantly lower in the intervention group after 20 months ( -25 min/d ; 95 % CI , -50 to -0.3 ) . No significant intervention effects on consumption of snacks or active commuting to school were found . CONCLUSION The Dutch Obesity Intervention in Teenagers program result ed in beneficial effects on the sum of skinfold thickness measurements in girls and consumption of sugar-containing beverages in both boys and girls in both the short and long terms OBJECTIVE : To evaluate the 6-month impact of a physical activity ( PA ) multilevel intervention on activity patterns and psychological predictors of PA among adolescents . The intervention was directed at changing knowledge and attitudes and at providing social support and environmental conditions that encourage PA of adolescents inside and outside school . SUBJECTS AND DESIGN : R and omised , controlled ongoing field trial ( ICAPS ) in middle-school 's first-level adolescents from eight schools selected in the department of the Bas-Rhin ( Eastern France ) with a cohort of 954 adolescents ( 92 % of the eligible students ) initially aged 11.7±0.6 y. The 6-month changes in participation in leisure organised PA ( LOPA ) , high sedentary ( SED ) behaviour ( > 3h/day ) , self-efficacy ( SELF ) and intention ( INTENT ) towards PA were analysed after controlling for baseline measures and different covariables ( age , overweight , socioprofessional occupation ) , taking into account the cluster r and omisation design . RESULTS : The proportion of intervention adolescents not engaged in organised PA was reduced by 50 % whereas it was unchanged among control students . After adjustment for baseline covariables , LOPA participation significantly increased among the intervention adolescents ( odds ratio ( 95 % confidence interval ) (OR)=3.38 ( 1.42–8.05 ) in girls ; 1.73 ( 1.12–2.66 ) in boys ) , while high SED was reduced ( OR=0.54 ( 0.38–0.77 ) in girls ; 0.52 ( 0.35–0.76 ) in boys ) . The intervention improved SELF in girls , whatever their baseline LOPA ( P<10−4 ) and INTENT in girls with no baseline LOPA ( P=0.04 ) . SELF tended to improve in boys with no baseline LOPA , without reaching statistical significance . When included in the regression , follow-up LOPA was associated with improvement of SELF in girls ( P=0.02 ) and of INTENT in girls with no baseline PA ( P<0.02 ) . The intervention effect was then attenuated . CONCLUSION : After 6 months of intervention , ICAPS was associated with a significant improvement of activity patterns and psychological predictors , indicating a promising approach for modifying the long-term PA level of adolescents Background : Because physical inactivity poses serious health risks , interventions are urgently needed to reverse the increasingly sedentary lifestyles of adolescent girls . Objective : The aim of this study was to determine the feasibility of " Girls on the Move , " an individually tailored computerized physical activity ( PA ) program plus nurse counseling intervention , in increasing PA . Methods : A pretest-posttest control group design was used with 77 racially diverse sedentary girls in Grade s 6 , 7 , and 8 from two middle schools . Each of the instructional grade s was r and omly assigned to either an intervention or control condition . After completing computerized question naires , each girl in the control group received a h and out listing the PA recommendations . To encourage PA , each girl in the intervention group received computerized , individually tailored feedback messages based on her responses to the question naires , individual counseling from the school 's pediatric nurse practitioner ( PNP ) , and telephone calls and mailings from a trained research assistant . At 12 weeks , girls in both groups responded to the question naires . Results : No differences in self-reported PA emerged between the intervention and control groups at Weeks 1 ( baseline ) and 12 ( postintervention ) . Repeated measures ANOVA showed a significant interaction between group and time for social support for PA , F(1 , 69 ) = 5.73 , p = .019 , indicating that the intervention group had significantly greater social support across time than did the control group . From baseline to postintervention , social support increased for the intervention group but decreased for the control group . Discussion : Reasons for the lack of significant differences between the groups on the PA measures were cited . Important information that could inform subsequent studies that test interventions to increase youth PA was acquired from conducting this study . Future efforts to increase PA participation might include this approach for enhancing social support for PA This study examined the effectiveness of an intervention to increase levels of moderate-to-vigorous intensity physical activity ( MVPA ) during girls ' physical education lessons . Two Year 7 classes ( age 11 - 12 years ) were r and omly appointed to control and experimental groups . Both followed the same six-lesson unit of gymnastics with identical lesson objectives . The experimental class teacher included the additional objective of increasing MVPA during each lesson . MVPA was assessed in all six lessons using heart rate ( HR ) monitoring and systematic observation . After each lesson , students ' intrinsic motivation and perceived competence were assessed , and the teachers evaluated whether they had met planned objectives . The experimental group engaged in more MVPA [ F(1 , 21 ) = 8.49 , P = 0.008 ( HR ) , t8 = -2.35 , P = 0.048 ( observation ) ] than the control group and also had most opportunities for skill practice ( t8 = -2.81 , P = 0.023 ) . Intrinsic motivation and perceived competence levels were similar between the groups for each lesson , and teachers reported that lesson objectives were satisfactorily achieved . This intervention succeeded in increasing MVPA without compromising intrinsic motivation , perceived competence or planned lesson objectives OBJECTIVES ICAPS ( Intervention Centred on Adolescents ' Physical activity and Sedentary behaviour ) is aim ed at preventing excessive weight gain and cardiovascular risk in adolescents by promoting physical activity ( PA ) with an emphasis on recreational and daily-life PA , with a lifelong perspective . DESIGN R and omized study design ed to last for four years . Study cohort constituted of 954 first-level students ( 91 % of eligible pupils ) , aged 11.7 + /- 0.6 y ( mean + /- SD ) from four pairs of schools r and omly selected in eastern France , after sociogeographical stratification . In each pair , intervention status was r and omised at school-level . The program , not limited to school setting s , involves multiple partners with three objectives : 1 ) changing attitudes through debates and access to attractive activities during breaks and after-school hours , 2 ) encouraging social support , 3 ) providing environmental conditions that enable PA . Adapted times and places , open participation , emphasis on fun , meeting with others and absence of competitive aspects are used to reduce usual barriers to PA . Accessibility and safety are permanent concerns . RESULTS Prevalence of overweight was 23.7 % . High participation rates were attained ( 50 % participated in at least one weekly activity ) . At six-month , the proportion of intervention adolescents not performing supervised PA out of academic PA was reduced by half ( 36 % to 17 % vs 42 % to 42 % in controls P < 10 - 4 ) ; the proportion of those spending > 3 h/day in sedentary occupations decreased ( 34 % to 28 % vs 27 % to 36 % ; P < 10 - 4 ) . CONCLUSION These data demonstrate the feasibility of implementing a multilevel PA intervention program in adolescents . Six-month results document increased PA and decreased sedentary behaviour BACKGROUND Although adolescence is a time when physical activity levels decline , few interventions have targeted high school-aged girls in the school setting . OBJECTIVE To evaluate the effects of a life skills-oriented physical activity intervention for increasing overall physical activity in high school-aged girls . DESIGN R and omized controlled trial . SETTING Baltimore magnet high school . PARTICIPANTS A total of 221 ninth- grade girls , 83.0 % of whom were African American . Intervention Participants were r and omized to an 8-month physical intervention conducted in physical education class or to a st and ard physical education class ( control ) . MAIN OUTCOME MEASURES Output:	Due to this lack of information , it is difficult to determine whether or not reportedly successful interventions are feasible and sustainable in an uncontrolled , real-world setting .
MS22131	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Hyperinsulinemia may explain excess colorectal cancer among individuals who are overweight or inactive . Recent studies have observed elevated colorectal cancer risk among individuals with elevated insulin levels 2 hours after oral glucose challenge or with elevated plasma C-peptide levels . The effect of consuming a high glycemic diet on colorectal risk , however , remains uncertain . Two prospect i ve cohort studies , the Nurses ' Health Study and the Health Professionals Follow-up Study , contributed up to 20 years of follow-up . After exclusions , 1,809 incident colorectal cancers were available for analyses . Dietary glycemic load ( GL ) was calculated as a function of glycemic index ( postpr and ial blood glucose response as compared with a reference food ) , carbohydrate content , and frequency of intake of individual foods reported on food frequency question naires . Multivariable Cox proportional hazards models were used to adjust for potential confounders . Intakes of dietary carbohydrate , GL , overall glycemic index , sucrose , and fructose were not associated with colorectal cancer risk in women . A small increase in risk was observed in men with high dietary GL ( multivariate relative risk , 1.32 ; 95 % confidence interval , 0.98 - 1.79 ; highest versus lowest quintile ) , sucrose or fructose ( multivariate relative risk , 1.37 ; 95 % confidence interval , 1.05 - 1.78 ; highest versus lowest quintile of fructose , P = 0.008 ) . Associations were slightly stronger among men with elevated body mass index ( > or = 25 kg/m(2 ) ) . Results among women were similar after stratifying by body mass index or physical activity . High intakes of GL , fructose , and sucrose were related to an elevated colorectal cancer risk among men . For women , however , these factors did not seem to increase the risk of colorectal cancer The determine the effect of different foods on the blood glucose , 62 commonly eaten foods and sugars were fed individually to groups of 5 to 10 healthy fasting volunteers . Blood glucose levels were measured over 2 h , and expressed as a percentage of the area under the glucose response curve when the same amount of carbohydrate was taken as glucose . The largest rises were seen with vegetables ( 70 + /- 5 % ) , followed by breakfast cereals ( 65 + /- 5 % ) , cereals and biscuits ( 60 + /- 3 % ) , fruit ( 50 + /- 5 % ) , dairy products ( 35 + /- 1 % ) , and dried legumes ( 31 + /- 3 % ) . A significant negative relationship was seen between fat ( p less than 0.01 ) and protein ( p less than 0.001 ) and postpr and ial glucose rise but not with fiber or sugar content To investigate the relation of dietary intakes of sucrose , meat , and fat , and anthropometric , lifestyle , hormonal , and reproductive factors to colon cancer incidence , data were analyzed from a prospect i ve cohort study of 35,215 Iowa ( United States ) women , aged 55–69 years and without a history of cancer , who completed mailed dietary and other question naires in 1986 . Through 1990 , 212 incident cases of colon cancer were documented . Proportional hazards regression was used to adjust for age and other risk factors . Risk factors found to be associated significantly with colon cancer included : ( i ) sucrose-containing foods and beverages other than ice cream/milk ; relative risks ( RR ) across the quintiles=1.00 , 1.73 , 1.56 , 1.54 , and 2.00 ( 95 % confidence intervals [ CI ] for quintiles two and five exclude 1.0 ) ; ( ii ) sucrose ; RR across the quintiles=1.00 , 1.70 , 1.81 , 1.82 , and 1.45 ( CI for quintiles two through four exclude 1.0 ) ; ( iii ) height ; RR=1.23 for highest to lowest quintile ( P for trend-0.02 ) ; ( iv ) body mass index ; RR=1.41 for highest to lowest quintile ( P for trend=0.03 ) ; and ( v ) number of livebirths , RR=1.59 for having had one to two livebirths and 1.80 for having had three or more livebirths compared with having had none ( P for trend=0.04 ) . These data support hypotheses that sucrose intake or being tall or obese increases colon cancer risk ; run contrary to the hypothesis that increased parity decreases risk ; support previous findings of no association with demographic factors other than age , cigarette smoking , or use of oral contraceptives or estrogen replacement therapy ; and raise questions regarding previous associations with meat , fat , protein , and physical activity . Cancer Causes and Control 1994 , 5 , 38–52 Although diet is believed to influence colorectal cancer risk , the long-term effects of a diet with a high glycemic load are unclear . The growing recognition that colorectal cancer may be promoted by hyperinsulinemia and insulin resistance suggests that a diet inducing high blood glucose levels and an elevated insulin response may contribute to a metabolic environment conducive to tumor growth . We prospect ively followed a cohort of 38 451 women for an average of 7.9 years and identified 174 with incident colorectal cancer . We used baseline dietary intake measurements , assessed with a semiquantitative food-frequency question naire , to examine the associations of dietary glycemic load , overall dietary glycemic index , carbohydrate , fiber , nonfiber carbohydrate , sucrose , and fructose with the subsequent development of colorectal cancer . Cox proportional hazards models were used to estimate relative risks ( RRs ) . Dietary glycemic load was statistically significantly associated with an increased risk of colorectal cancer ( adjusted RR = 2.85 , 95 % confidence interval [ CI ] = 1.40 to 5.80 , comparing extreme quintiles of dietary glycemic load ; P(trend ) = .004 ) and was associated , although not statistically significantly , with overall glycemic index ( corresponding RR = 1.71 , 95 % CI = 0.98 to 2.98 ; P(trend ) = .04 ) . Total carbohydrate ( adjusted RR = 2.41 , 95 % CI = 1.10 to 5.27 , comparing extreme quintiles of carbohydrate ; P(trend ) = .02 ) , nonfiber carbohydrate ( corresponding RR = 2.60 , 95 % CI = 1.22 to 5.54 ; P(trend ) = .02 ) , and fructose ( corresponding RR = 2.09 , 95 % CI = 1.13 to 3.87 ; P(trend ) = .08 ) were also statistically significantly associated with increased risk . Thus , our data indicate that a diet with a high dietary glycemic load may increase the risk of colorectal cancer in women The relation between diet and female colorectal cancer was analyzed in a prospect i ve study of 14,727 women aged 34 - 65 years , who were enrolled at mammographic screening clinics in New York and Florida from 1985 to 1991 . They were followed through the end of 1994 ( average 7.1 yrs ) by a combination of direct contact through mail and telephone and record linkages with regional tumor registries , result ing in 100 incident cases of colorectal cancer . There was no overall positive or inverse association of colorectal cancer risk with intakes of total calories , total or subclasses of fat , carbohydrate , or dietary fiber , whereas there was an inverse association with total protein . Among major food groups , there was a progressive decline in risk of colorectal cancer with increasing intake of fish and shellfish ( relative risk for 4th vs. 1st quartile = 0.49 , 95 % confidence interval = 0.27 - 0.89 ) . A similar inverse association was also observed for consumption of dairy products , and this association was explained mainly by calcium , not by other nutrients , such as fat or protein . The results of the present study indicated that certain dietary components of fish or dairy products may protect against colorectal cancer , whereas the relations with red meat or total fat remained unclear Diet has long been thought to be an important factor in the etiology of colorectal cancer . The specific dietary nutrients or factors responsible for this disease , the second leading cause of cancer death in the United States [ 1 ] , have not , however , been clearly eluci date d. Colorectal adenomatous polyps ( here referred to as polyps ) are generally considered to be precursor lesions for most cases of colorectal carcinoma [ 2 - 4 ] ; however , little is known about their risk factors . Since the introduction of fiberoptic endoscopy , especially colonoscopy , attention has focused on the potential for preventing colorectal cancer by screening for and resecting the adenomas [ 5 , 6 ] . Because of their high recurrence rate after resection [ 7 , 8 ] , these polyps have been used as an end point for the study of potential chemopreventive agents . Four studies have explored potential dietary risk factors for incident colorectal adenomatous polyps [ 9 - 12 ] . No previous observational studies have explored the role of diet or other lifestyle factors in the recurrence of polyps after polypectomy . We discuss the results of a casecontrol study of colorectal polyps among patients from three colonoscopy practice s and analyze dietary risk factors for both incident and recurrent polyps . Methods Our study sample included patients having colonoscopy at three colonoscopy practice s in New York City between April 1986 and March 1988 . In total , 2988 patients were evaluated . Of these , 2443 ( 81.8 % ) were eligible for our study ( patients had to be between 35 and 84 years of age ; reside in New York , New Jersey , or Connecticut ; speak English or Spanish ; and have colonoscopy to at least the splenic flexure ) . The colonoscopists completed data sheets indicating the reason for colonoscopy and the clinical findings at the time of colonoscopy . The study pathologist review ed slides of all suspected neoplastic lesions . All eligible participants received a letter signed by their colonoscopist introducing the study . A trained interviewer then contacted and interviewed participants by telephone . Alternatively , the question naire was mailed for self-completion and was followed by a telephone interview to resolve any remaining questions . An earlier study indicated that the results obtained for dietary factors were similar for both interview methods [ 13 ] . The interview itself consisted of a general question naire that focused on demographic characteristics , medical history , lifestyle , family history , and other topics . The dietary interview consisted of the Block food frequency question naire and specified food intake for a period 3 to 5 years before the colonoscopy [ 14 ] . Ultimately , 1956 dietary question naires were completed ( 80.1 % of eligible patients ) . Of these , 71 % were conducted by telephone , and 29 % were returned by mail . An incident case of adenomatous polyps was defined as an eligible participant with no history of colon carcinoma , adenomatous polyps , or inflammatory bowel disease who was found to have one or more pathologically defined polyps on the index colonoscopy . The incident control group consisted of persons who were found to be free of colorectal neoplasia on index colonoscopy and who were without a history of adenomatous polyps , colon cancer , or inflammatory bowel disease . A case of recurrent polyps was defined as an eligible participant with a self-reported history of one or more polyps who had a pathologically confirmed polyp on the index colonoscopy . The recurrent control was defined as a participant whose index colonoscopy showed no colorectal neoplasia but who had a history of one or more polyps . Cases and controls with a history of colorectal cancer or inflammatory bowel disease were excluded . Although we did not have pathologic confirmation of all initial polyps , we did obtain pathology reports on a r and om sample of 100 recurrent cases and controls and found 97 to be adenomatous . By these criteria , 286 incident cases ( 162 men and 124 women ) and 480 incident controls ( 210 men and 270 women ) were identified , whereas 186 recurrence cases ( 130 men and 56 women ) and 330 recurrence controls ( 187 men and 143 women ) were found . Food item and nutrient data were generated by software programs provided by Block and coworkers [ 14 ] at the National Cancer Institute . The main analyses were done using logistic regression modelling and maximum likelihood ratios [ 15 ] in the BMDP-LR program . Analyses were conducted separately for men and women . Age , Quetelet index , and caloric intake were entered as covariates for most analyses . A previous study by our group had shown obesity , as measured by Quetelet index , to be a risk factor for polyps among women ; the trend for men was not significant [ 16 ] . Analyses in which nutrients were st and ardized per 1000 kilocalories were also done for comparison [ 17 ] . For each nutrient or food group , quartiles were defined by review of the control group data ; the lowest quartile was given a reference value of 1.0 , and odds ratios were calculated for each of the other quartiles , with 95 % confidence intervals ( CIs ) for the highest-to-lowest quartile comparison . The Output:	Conclusion This meta- analysis of cohort studies does not support an independent association between diets high in carbohydrate , glycemic index , or glycemic load and colorectal cancer risk
MS22132	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Patients with type 2 diabetes mellitus ( T2DM ) with a glycated haemoglobin ( HbA1c ) level ≥7 and ≤10 % were r and omized to receive empagliflozin 12.5 mg twice daily ( n = 219 ) , 25 mg once daily ( n = 218 ) , 5 mg twice daily ( n = 219 ) or 10 mg once daily ( n = 220 ) , or placebo ( n = 107 ) as add‐on to stable‐dose metformin immediate release ( IR ) twice daily for 16 weeks . The primary endpoint was change from baseline in HbA1c at week 16 . At week 16 , change from baseline in HbA1c with empagliflozin twice daily was non‐inferior to empagliflozin once daily and vice versa . The adjusted mean ( 95 % confidence interval ) difference in change from baseline in HbA1c with empagliflozin 12.5 mg twice daily versus 25 mg once daily was −0.11 % ( −0.26 , 0.03 ) , and with empagliflozin 5 mg twice daily versus 10 mg once daily it was −0.02 % ( −0.16 , 0.13 ) . All empagliflozin regimens were well tolerated ; thus , when used as add‐on to metformin IR in patients with T2DM , the therapeutic effect of empagliflozin twice‐daily and once‐daily regimens can be considered equivalent OBJECTIVE To evaluate the efficacy and safety of dapagliflozin in patients with type 2 diabetes inadequately controlled with metformin and sulfonylurea . RESEARCH DESIGN AND METHODS Patients with HbA1c of 7.0 % ( 53 mmol/mol ) to 10.5 % ( 91 mmol/mol ) receiving sulfonylurea and metformin were r and omized to receive dapagliflozin 10 mg/day ( n = 109 ) or placebo ( n = 109 ) for 24 weeks . RESULTS HbA1c ( baseline : dapagliflozin 8.08 % [ 65 mmol/mol ] ; placebo 8.24 % [ 67 mmol/mol ] ) and fasting plasma glucose ( baseline : dapagliflozin 167.4 mg/dL [ 9.29 mmol/L ] ; placebo 180.5 mg/dL [ 10.02 mmol/L ] ) significantly improved from baseline with dapagliflozin ( placebo-subtracted change –0.69 % [ –7.5 mmol/mol ] , P < 0.0001 ; –33.5 mg/dL [ –1.86 mmol/L ] , P < 0.0001 , respectively ) . More patients achieved a therapeutic glycemic response ( HbA1c < 7.0 % [ 53 mmol/mol ] ) with dapagliflozin ( 31.8 % ) versus placebo ( 11.1 % ) ( P < 0.0001 ) . Body weight and systolic blood pressure were significantly reduced from baseline over 24 and 8 weeks , respectively , with dapagliflozin ( placebo-subtracted change –2.1 kg , P < 0.0001 ; –3.8 mmHg , P = 0.0250 ) . Patients receiving dapagliflozin showed placebo-subtracted increases in total , LDL , and HDL cholesterol ( 11.4 mg/dL , P = 0.0091 ; 11.4 mg/dL , P = 0.0030 ; 2.2 mg/dL , P = 0.0172 , respectively ) with no change in LDL/HDL cholesterol ratio ( 0.1 ; P = 0.2008 ) or triglycerides ( –16.5 mg/dL ; P = 0.1755 ) . Adverse events occurred in 48.6 % of patients receiving dapagliflozin and 51.4 % receiving placebo . Significantly more patients with dapagliflozin compared with placebo experienced hypoglycemia ( 12.8 vs. 3.7 % ; P = 0.024 ) and genital infections ( 5.5 vs. 0 % ; P = 0.029 ) . Events of urinary tract infection were reported by 6.4 % of patients in both groups . CONCLUSIONS Dapagliflozin was well tolerated and effective over 24 weeks as add-on to metformin plus sulfonylurea . Adverse effects included hypoglycemia and genital infections OBJECTIVE To investigate the efficacy , safety , and tolerability of empagliflozin in patients with type 2 diabetes and hypertension . RESEARCH DESIGN AND METHODS Patients ( N = 825 ) with type 2 diabetes and hypertension ( mean seated systolic blood pressure [ SBP ] 130–159 mmHg and diastolic blood pressure [ DBP ] 80–99 mmHg ) were r and omized ( double blind ) to 10 mg or 25 mg empagliflozin or placebo once daily for 12 weeks . RESULTS At week 12 , adjusted mean difference versus placebo in change from baseline in mean 24-h SBP ( ambulatory blood pressure monitoring [ ABPM ] ) was −3.44 mmHg ( 95 % CI −4.78 , −2.09 ) with 10 mg empagliflozin and −4.16 mmHg ( −5.50 , −2.83 ) with 25 mg empagliflozin ( both P < 0.001 ) . At week 12 , adjusted mean difference versus placebo in change from baseline in mean 24-h DBP ( ABPM ) was −1.36 mmHg ( 95 % CI −2.15 , −0.56 ) with 10 mg empagliflozin and −1.72 mmHg ( 95 % CI −2.51 , −0.93 ) with 25 mg empagliflozin ( both P < 0.001 ) . Changes in office BP were consistent with ABPM . Adjusted mean difference versus placebo in change from baseline in HbA1c at week 12 was −0.62 % ( 95 % CI −0.72 , −0.52 ) ( −6.8 mmol/mol [ 95 % CI −7.9 , −5.7 ] ) with 10 mg empagliflozin and −0.65 % ( 95 % CI −0.75 , −0.55 ) ( −7.1 mmol/mol [ 95 % CI −8.2 , −6.0 ] ) with 25 mg empagliflozin ( both P < 0.001 ) . Empagliflozin was well tolerated . One patient on placebo and one patient on 10 mg empagliflozin reported events consistent with volume depletion . CONCLUSIONS Empagliflozin was associated with significant and clinical ly meaningful reductions in BP and HbA1c versus placebo and was well tolerated in patients with type 2 diabetes and hypertension Background This study evaluated the effect of empagliflozin on postpr and ial glucose ( PPG ) and 24-hour glucose variability in Japanese patients with type 2 diabetes mellitus ( T2DM ) . Methods Patients ( N = 60 ; baseline mean [ SD ] HbA1c 7.91 [0.80]% ; body mass index 24.3 [ 3.2 ] kg/m2 ) were r and omized to receive empagliflozin 10 mg ( n = 20 ) , empagliflozin 25 mg ( n = 19 ) or placebo ( n = 21 ) once daily as monotherapy for 28 days . A meal tolerance test and continuous glucose monitoring ( CGM ) for 24 hours were performed at baseline and on days 1 and 28 . The primary endpoint was change from baseline in area under the glucose concentration-time curve 3 hours after breakfast ( AUC1–4h for PPG ) at day 28 . Results Adjusted mean ( 95 % ) differences versus placebo in changes from baseline in AUC1 - 4h for PPG at day 1 were −97.1 ( −126.5 , −67.8 ) mg · h/dl with empagliflozin 10 mg and −91.6 ( −120.4 , −62.8 ) mg · h/dl with empagliflozin 25 mg ( both p < 0.001 versus placebo ) and at day 28 were −85.5 ( −126.0 , −45.0 ) mg · h/dl with empagliflozin 10 mg and −104.9 ( −144.8 , −65.0 ) mg · h/dl with empagliflozin 25 mg ( both p < 0.001 versus placebo ) . Adjusted mean ( 95 % CI ) differences versus placebo in change from baseline in 24-hour mean glucose ( CGM ) at day 1 were −20.8 ( −27.0 , −14.7 ) mg/dl with empagliflozin 10 mg and −23.9 ( −30.0 , −17.9 ) mg/dl with empagliflozin 25 mg ( both p < 0.001 versus placebo ) and at day 28 were −24.5 ( −35.4 , −13.6 ) mg/dl with empagliflozin 10 mg and −31.7 ( −42.5,-20.9 ) mg/dl with empagliflozin 25 mg ( both p < 0.001 versus placebo ) . Changes from baseline in mean amplitude of glucose excursions ( MAGE ; CGM ) were not significantly different with either empagliflozin dose versus placebo at either timepoint . Curves of mean glucose ( CGM ) did not change between baseline and day 1 or 28 with placebo , but shifted downward with empagliflozin . Percentage of time with glucose ≥70 to < 180 mg/dl increased from 52.0 % at baseline to 77.0 % at day 28 with empagliflozin 10 mg and from 55.0 % to 81.1 % with empagliflozin 25 mg , without increasing time spent with hypoglycemia . Conclusion Empagliflozin for 28 days reduced PPG from the first day and improved daily blood glucose control in Japanese patients with T2DM.Trial registration Clinical trials.gov OBJECTIVE We investigated the efficacy and safety of the sodium glucose cotransporter 2 inhibitor , empagliflozin , added to multiple daily injections of insulin ( MDI insulin ) in obese patients with type 2 diabetes mellitus ( T2DM ) . RESEARCH DESIGN AND METHODS Patients inadequately controlled on MDI insulin ± metformin ( mean HbA1c 8.3 % [ 67 mmol/mol ] ; BMI 34.8 kg/m2 ; insulin dose 92 international units/day ) were r and omized and treated with once-daily empagliflozin 10 mg ( n = 186 ) , empagliflozin 25 mg ( n = 189 ) , or placebo ( n = 188 ) for 52 weeks . Insulin dose was to remain stable in weeks 1–18 , adjusted to meet glucose targets in weeks 19–40 , then stable in weeks 41–52 . The primary end point was change from baseline in HbA1c at week 18 . Secondary end points were changes from baseline in insulin dose , weight , and HbA1c at week 52 . RESULTS Adjusted mean ± SE changes from baseline in HbA1c were −0.50 ± 0.05 % ( −5.5 ± 0.5 mmol/mol ) for placebo versus −0.94 ± 0.05 % ( −10.3 ± 0.5 mmol/mol ) and −1.02 ± 0.05 % ( −11.1 ± 0.5 mmol/mol ) for empagliflozin 10 mg and empagliflozin 25 mg , respectively , at week 18 ( both P < 0.001 ) . At week 52 , further reductions with insulin titration result ed in changes from baseline in HbA1c of −0.81 ± 0.08 % ( −8.9 ± 0.9 mmol/mol ) , −1.18 ± 0.08 % ( −12.9 ± 0.9 mmol/mol ) , and −1.27 ± 0.08 % ( −13.9 ± 0.9 mmol/mol ) with placebo , empagliflozin 10 mg , and empagliflozin 25 mg , respectively , and final HbA1c of 7.5 % ( 58 mmol/m Output:	SGLT2 inhibition was not associated with significant changes in eGFR in patients with type 2 diabetes , likely result ing from a mixture of an initial reduction of eGFR and long-term renal function preservation . SGLT2 inhibition was associated with statistically significant albuminuria reduction in type 2 diabetic patients with CKD
MS22133	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Few controlled studies have compared the efficacy of clozapine and risperidone in treatment-refractory schizophrenic patients . The present study investigates the efficacy of both clozapine and risperidone on psychopathologic and neurocognitive measures in a prospect i ve 12-week open-label trial in treatment-refractory schizophrenic patients from state psychiatric hospitals . METHOD Thirty-five DSM-IV schizophrenic patients with a documented history of nonresponse to typical neuroleptics were treated with either clozapine or risperidone . Response was assessed every 2 weeks by independent raters with the Positive and Negative Syndrome Scale ( PANSS ) , the Clinical Global Impressions ( CGI ) scale , neurologic rating scales , and plasma drug levels . Neurocognitive tests were administered at baseline and week 12 . RESULTS Both clozapine and risperidone brought about significant ( p < .003 ) overall improvement in psychopathology . However , clozapine was numerically superior to risperidone on PANSS total scores and PANSS positive , negative , excitement , and cognitive factors . Extrapyramidal side effects were minimal for clozapine , whereas some were present for risperidone . Patients taking risperidone improved significantly in the beginning stages of the study and remained stable thereafter . Patients taking clozapine showed a gradual improvement that occurred over the entire length of the trial . Neurocognitive measures showed minimal improvement and did not differentiate between the 2 medication groups . CONCLUSION Both clozapine and risperidone were comparably effective across a wide spectrum of psychopathologic measures . While the efficacy of clozapine was only numerically superior to that of risperidone , it was associated with fewer extrapyramidal side effects and with progressive improvement over the 12-week treatment period , suggesting that in longer trials clozapine may prove to be superior to risperidone in neuroleptic-refractory patients This 18-week , r and omized , flexible-dose , double-blind , double-dummy trial evaluated ziprasidone as an alternative to clozapine in treatment-refractory schizophrenia patients . Patients had a DSM-IV diagnosis of schizophrenia , a history of resistance and /or intolerance to at least three acute cycles with different antipsychotics given at therapeutic doses , PANSS score > or=80 , and CGI-S score > or=4 . Patients were r and omized to ziprasidone ( 80 - 160 mg/day , n=73 ) or clozapine ( 250 - 600 mg/day , n=74 ) . On the primary ITT-LOCF analysis , baseline-to-endpoint decreases in PANSS total scores were similar in the ziprasidone ( -25.0+/-22.0 , 95 % CI -30.2 to -19.8 ) and clozapine ( -24.5+/-22.5 , 95 % CI -29.7 to -19.2 ) groups . A progressive and significant reduction from baseline in PANSS total score was observed from day 11 in both study arms . There were also significant improvements on PANSS subscales , CGI-S , CG-I , CDSS , and GAF , without between-drug differences . The two treatment groups had similar rates of early discontinuations due to AEs . AEs were mostly of similar mild-moderate severity in the two groups . There were also no detrimental effects on prolactin , renal and liver function , hematology , and cardiovascular parameters . However , ziprasidone but not clozapine showed a significant reduction of SAS and AIMS scores . Moreover , when compared with clozapine , ziprasidone also had a more favorable metabolic profile , with significant endpoint differences in weight , fasting glucose , total cholesterol , LDL cholesterol , and triglycerides . In conclusion , this trial indicates that both ziprasidone and clozapine , having comparable efficacy coupled with satisfactory general safety and tolerability , may be regarded as valuable options for the short-term treatment of difficult-to-treat schizophrenia patients with a history of multiple resistance and /or intolerance to antipsychotics . The more favorable metabolic profile of ziprasidone may represent an added value that could guide clinicians , at least in the presence of patients at high risk for metabolic disorders OBJECTIVE When a schizophrenia patient has an inadequate response to treatment with an antipsychotic drug , it is unclear what other antipsychotic to switch to and when to use clozapine . In this study , the authors compared switching to clozapine with switching to another atypical antipsychotic in patients who had discontinued treatment with a newer atypical antipsychotic in the context of the Clinical Antipsychotic Trials for Interventions Effectiveness ( CATIE ) investigation . METHOD Ninety-nine patients who discontinued treatment with olanzapine , quetiapine , risperidone , or ziprasidone in phase 1 or 1B of the trials , primarily because of inadequate efficacy , were r and omly assigned to open-label treatment with clozapine ( N=49 ) or blinded treatment with another newer atypical antipsychotic not previously received in the trial ( olanzapine [ N=19 ] , quetiapine [ N=15 ] , or risperidone [ N=16 ] ) . RESULTS Time until treatment discontinuation for any reason was significantly longer for clozapine ( median=10.5 months ) than for quetiapine ( median=3.3 ) , or risperidone ( median=2.8 ) , but not for olanzapine ( median=2.7 ) . Time to discontinuation because of inadequate therapeutic effect was significantly longer for clozapine than for olanzapine , quetiapine , or risperidone . At 3-month assessment s , Positive and Negative Syndrome Scale total scores had decreased more in patients treated with clozapine than in patients treated with quetiapine or risperidone but not olanzapine . One patient treated with clozapine developed agranulocytosis , and another developed eosinophilia ; both required treatment discontinuation . CONCLUSIONS For these patients with schizophrenia who prospect ively failed to improve with an atypical antipsychotic , clozapine was more effective than switching to another newer atypical antipsychotic . Safety monitoring is necessary to detect and manage clozapine 's serious side effects The data for medical decision analyses are often unreliable . Traditional sensitivity analysis --varying one or more probability or utility estimates from baseline values to see if the optimal strategy changes -- is cumbersome if more than two values are allowed to vary concurrently . This paper describes a practical method for probabilistic sensitivity analysis , in which uncertainties in all values are considered simultaneously . The uncertainty in each probability and utility is assumed to possess a probability distribution . For ease of application we have used a parametric model that permits each distribution to be specified by two values : the baseline estimate and a bound ( upper or lower ) of the 95 percent confidence interval . Following multiple simulations of the decision tree in which each probability and utility is r and omly assigned a value within its distribution , the following results are recorded : ( a ) the mean and st and ard deviation of the expected utility of each strategy ; ( b ) the frequency with which each strategy is optimal ; ( c ) the frequency with which each strategy " buys " or " costs " a specified amount of utility relative to the remaining strategies . As illustrated by an application to a previously published decision analysis , this technique is easy to use and can be a valuable addition to the armamentarium of the decision analyst We examined the response to clozapine in 10 schizophrenic patients who had been followed prospect ively from the time of their first hospitalization and who were refractory to multiple clinical trials with typical Clozapine is the only antipsychotic in the United States that has been approved by the Food and Drug Administration ( FDA ) for treatment-resistant schizophrenia . It provides effective treatment even when patients do not respond to other secondgeneration antipsychotics . [ 1 ] It also remains the most effective antipsychotic available . No existing first or second-generation antipsychotic has been consistently found to be as effective as clozapine monotherapy in treatment-resistant patients . [ 2 - 6 ] Among patients who entered Phase 2 of the Clinical Antipsychotic Trial of Intervention Effectiveness ( CATIE ) because of lack of efficacy in Phase 1 of the study , those treated with clozapine ( open label ) averaged significantly greater time to treatment discontinuation ( 10.5 months ) compared to patients treated with other antipsychotic medications ( 2.7 - 3.3 months ) . At three months , total symptom scores also improved to a significantly greater degree in the clozapine group compared to those treated with risperidone or quetiapine . [ 7 ] Similarly , in the open-label , r and omized CUtLASS ( Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study ) trial , clozapine treatment was associated with significantly greater improvement in total scores of the Positive and Negative Symptom Scale ( PANSS ) and better patient subjective ratings compared to risperidone , olanzapine , quetiapine , and amisulpiride . [ 8 ] Another large , nonr and omized effectiveness study , the Schizophrenia Outpatient Health Outcomes ( SOHO ) study , also found clozapine to be superior on clinician and patient ratings at six months compared to other antipsychotics . [ 9 ] Based on clinical trials , meta-analyses , and large naturalistic studies clozapine is recommended as the most effective agent in schizophrenia , but the recommendations indicate that it should only be used when other agents fail . [ 5 BACKGROUND Approximately 50 % of patients with schizophrenia or schizoaffective disorder attempt suicide , and approximately 10 % die of suicide . Study results suggest that clozapine therapy significantly reduces suicidal behavior in these patients . METHODS A multicenter , r and omized , international , 2-year study comparing the risk for suicidal behavior in patients treated with clozapine vs olanzapine was conducted in 980 patients with schizophrenia or schizoaffective disorder , 26.8 % of whom were refractory to previous treatment , who were considered at high risk for suicide because of previous suicide attempts or current suicidal ideation . To equalize clinical contact across treatments , all patients were seen weekly for 6 months and then biweekly for 18 months . Subsequent to r and omization , unmasked clinicians at each site could make any interventions necessary to prevent the occurrence of suicide attempts . Suicidal behavior was assessed at each visit . Primary end points included suicide attempts ( including those that led to death ) , hospitalizations to prevent suicide , and a rating of " much worsening of suicidality " from baseline . Masked raters , including an independent suicide monitoring board , determined when end point criteria were achieved . RESULTS Suicidal behavior was significantly less in patients treated with clozapine vs olanzapine ( hazard ratio , 0.76 ; 95 % confidence interval , 0.58 - 0.97 ; P = .03 ) . Fewer clozapine-treated patients attempted suicide ( 34 vs 55 ; P = .03 ) , required hospitalizations ( 82 vs 107 ; P = .05 ) or rescue interventions ( 118 vs 155 ; P = .01 ) to prevent suicide , or required concomitant treatment with antidepressants ( 221 vs 258 ; P = .01 ) or anxiolytics or soporifics ( 301 vs 331 ; P = .03 ) . Overall , few of these high-risk patients died of suicide during the study ( 5 clozapine vs 3 olanzapine-treated patients ; P = .73 ) . CONCLUSIONS Clozapine therapy demonstrated superiority to olanzapine therapy in preventing suicide attempts in patients with schizophrenia and schizoaffective disorder at high risk for suicide . Use of clozapine in this population should lead to a significant reduction in suicidal behavior BACKGROUND Despite the demonstrated efficacy of clozapine in severely refractory schizophrenia , questions remain regarding its efficacy for primary negative symptoms , comparison with a moderate dose of a first-generation antipsychotic , and adverse effects during a longer-term trial . This study examined its efficacy in partially responsive , community-based patients , compared clozapine with moderate-dose haloperidol , and extended treatment to 6 months . METHODS R and omized , double-blind , 29-week trial comparing clozapine ( n = 37 ) with haloperidol ( n = 34 ) . Subjects with schizophrenia who were being treated in community setting s at 3 collaborating clinical facilities were enrolled . RESULTS Subjects treated with haloperidol were significantly more likely to discontinue treatment for lack of efficacy ( 51 % ) than were those treated with clozapine ( 12 % ) . A higher proportion of clozapine-treated subjects met an a priori criterion of improvement ( 57 % ) compared with haloperidol-treated subjects ( 25 % ) . Significantly greater improvement was seen in symptoms of psychosis , hostile-suspiciousness , anxiety-depression , thought disturbance , and total score measured on the Brief Psychiatric Rating Scale . No differences were detected in negative symptoms using the Brief Psychiatric Rating Scale or the Schedule for Assessment of Negative Symptoms . Subjects treated with clozapine experienced more excess salivation , dizziness , and sweating and less dry mouth and decreased appetite than those treated with haloperidol . CONCLUSIONS Compared with a first-generation antipsychotic given in a moderate dose , clozapine offers substantial clinical benefits to treatment- Output:	Cost savings were most sensitive to the proportion of treatment-resistant patients who received clozapine , decrease in inpatient days , cost of inpatient stays , clozapine response rate , and number of patients with treatment-resistant schizophrenia . Increased clozapine utilization would result in net cost savings for the VHA
MS22134	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: CONTEXT To enhance the effectiveness of diet in lowering cholesterol , recommendations of the Adult Treatment Panel III of the National Cholesterol Education Program emphasize diets low in saturated fat together with plant sterols and viscous fibers , and the American Heart Association supports the use of soy protein and nuts . OBJECTIVE To determine whether a diet containing all of these recommended food components leads to cholesterol reduction comparable with that of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ( statins ) . DESIGN R and omized controlled trial conducted between October and December 2002 . SETTING AND PARTICIPANTS Forty-six healthy , hyperlipidemic adults ( 25 men and 21 postmenopausal women ) with a mean ( SE ) age of 59 ( 1 ) years and body mass index of 27.6 ( 0.5 ) , recruited from a Canadian hospital-affiliated nutrition research center and the community . INTERVENTIONS Participants were r and omly assigned to undergo 1 of 3 interventions on an outpatient basis for 1 month : a diet very low in saturated fat , based on milled whole-wheat cereals and low-fat dairy foods ( n = 16 ; control ) ; the same diet plus lovastatin , 20 mg/d ( n = 14 ) ; or a diet high in plant sterols ( 1.0 g/1000 kcal ) , soy protein ( 21.4 g/1000 kcal ) , viscous fibers ( 9.8 g/1000 kcal ) , and almonds ( 14 g/1000 kcal ) ( n = 16 ; dietary portfolio ) . MAIN OUTCOME MEASURES Lipid and C-reactive protein levels , obtained from fasting blood sample s ; blood pressure ; and body weight ; measured at weeks 0 , 2 , and 4 and compared among the 3 treatment groups . RESULTS The control , statin , and dietary portfolio groups had mean ( SE ) decreases in low-density lipoprotein cholesterol of 8.0 % ( 2.1 % ) ( P = .002 ) , 30.9 % ( 3.6 % ) ( P<.001 ) , and 28.6 % ( 3.2 % ) ( P<.001 ) , respectively . Respective reductions in C-reactive protein were 10.0 % ( 8.6 % ) ( P = .27 ) , 33.3 % ( 8.3 % ) ( P = .002 ) , and 28.2 % ( 10.8 % ) ( P = .02 ) . The significant reductions in the statin and dietary portfolio groups were all significantly different from changes in the control group . There were no significant differences in efficacy between the statin and dietary portfolio treatments . CONCLUSION In this study , diversifying cholesterol-lowering components in the same dietary portfolio increased the effectiveness of diet as a treatment of hypercholesterolemia The daily consumption of fruits and vegetables is a common dietary recommendation to support good health . We hypothesized that a commercially available encapsulated fruit and vegetable juice powder concentrate ( FVJC ) could support functional indices of health due to increased intake of various phytonutrients . This was a double-blind , r and omized , placebo-controlled investigation of 59 healthy law students who consumed either FVJC or placebo capsules for 77 d. Blood was collected on d 1 , 35 , and 77 to examine the number of circulating alphabeta- and gammadelta-T cells , cytokine production , lymphocyte DNA damage , antioxidant status , and levels of carotenoids and vitamin C. A log of illnesses and symptoms was also kept . The FVJC group tended to have fewer total symptoms than the placebo group ( P < 0.076 ) . By d 77 there was a 30 % increase in circulating gammadelta-T cells and a 40 % reduction in DNA damage in lymphocytes in the FVJC group relative to the placebo group . Plasma levels of vitamin C and of beta-carotene , lycopene , and lutein increased significantly from baseline in the FVJC group as did plasma oxygen radical absorptive capacity ( 50 % ) . Interferon-gamma produced by phorbol-stimulated lymphocytes was reduced 70 % in the FVJC group , whereas other cytokines ( IL-4 , IL-6 , transforming growth factor beta ) were unchanged relative to treatment or time . FVJC consumption during this study period result ed in increased plasma nutrients and antioxidant capacity , reduction in DNA str and breaks , and an increase in circulating gammadelta-T cells Phytonutrients from plant foods provide numerous antioxidants . We hypothesized that supplementation for 28 wk with a commercially available encapsulated juice powder concentrate ( JPC ) could influence indicators of oxidative stress , immunity , and illness . Trained men ( n = 41 ; 34 + /- 5 y ; maximum oxygen uptake = 55 + /- 7 mL x kg(-1 ) x min(-1 ) ) from a homogenous police Special Forces unit were r and omly assigned in a double blind manner to either JPC ( n = 21 ) or placebo ( n = 20 ) . We used multiple 7-d food records to assess dietary intake and found inadequate mean daily fruit and vegetable consumption ( 3.2 + /- 1.2 servings ) . The group physician documented all duty days lost due to illness . We collected plasma at baseline and study wk 4 , 8 , 16 , and 28 for analysis of carbonyl groups on protein ( CP ) and TNFalpha . Over the 28-wk investigation , CP was lower in the JPC group , with both a treatment and a time x treatment interaction ( P < 0.05 ) . Concentrations of both CP and TNFalpha at 16 and 28 wk were lower in the JPC than in the placebo group ( P < 0.001 ) . TNFalpha increased during the first 8 wk followed by a decrease in both groups for the following 20 wk ( P < 0.001 ) . Over the final 20 wk of the study , the placebo group tended to have more days of illness than the JPC group ( P = 0.068 ) . These data suggest beneficial JPC effects with regard to reduction of duty days lost due to illness and reduction of CP and TNFalpha concentrations in this group of trained men over 28 wk Fruit and vegetable consumption is inversely associated with coronary heart disease ( CHD ) risk . The aim of the present study was to determine the effect of supplementation with dehydrated juice concentrates from mixed fruit and vegetables on selected plasma vitamins and antioxidant status . We assessed CHD risk by measuring the concentrations of homocysteine , lipids , lipoproteins , glucose and insulin . Men were recruited to participate in a r and omized double-blind , crossover trial with 2 periods of 6 wk , separated by a 3-wk wash-out period . Supplementation with the encapsulated mixed extract ( Juice Plus ) was compared with physically similar placebo capsules . Thirty-two men ( 13 smokers , 19 nonsmokers ) completed the study with a mean compliance of 88 % . Compared with placebo , supplementation increased the concentrations of plasma beta-carotene ( 0.24 + /- 0.15 vs. 1.12 + /- 0.70 micro mol/L ; mean + /- SD ; P < 0.0001 ) , retinol ( 1.87 + /- 0.33 vs. 2.00 + /- 0.43 micro mol/L ; P < 0.05 ) , alpha-tocopherol ( 16.8 + /- 7.3 vs. 19.3 + /- 6.8 micro mol/L ; P < 0.01 ) , ascorbic acid ( 72.1 + /- 19.4 vs. 84.1 + /- 13.5 micro mol/L ; P < 0.002 ) and folic acid ( 24.5 + /- 10.0 vs. 44.9 + /- 16.9 nmol/L ; P < 0.0001 ) . Plasma homocysteine was reduced ( 8.2 + /- 1.5 vs. 7.6 + /- 1.1 ; P < 0.05 ) and inversely related ( r = -0.40 , P < 0.001 ) with serum folate concentrations . Plasma vitamin C was positively correlated with the resistance of LDL to oxidation ( r = 0.26 , P < 0.05 ) and the plasma ferric reducing/antioxidant power ( FRAP ) tended to be greater after supplementation than after the placebo period ( 1125.5 + /- 144.1 vs. 1180.3 + /- 158.1 micro mol/L ; P < 0.065 ) . Plasma glucose , insulin and lipid concentrations were unaffected . Responses of smokers and nonsmokers did not differ . In the absence of dietary modification , supplementation with a fruit and vegetable concentrate produced responses consistent with a reduction in CHD risk OBJECTIVES Our objective was to determine if long-term daily administration of phytonutrient supplements can prevent the immediate adverse impact of a high-fat meal and increase the production of nitric oxide . BACKGROUND Ingestion of a high-fat meal impairs flow-mediated vasodilation of the brachial artery for at least 4 h ; however , co-ingestion of vitamin antioxidants or a green salad has been shown to prevent this effect . METHODS Flow-mediated brachial artery reactivity test ( BART ) both before and 3 h after a 900 calorie 50 g fat meal was evaluated in 38 healthy volunteers ( age 36.4 + /- 10.1 years ) . Subjects were r and omized to four weeks of daily supplementation with a powdered fruit vegetable juice concentrate ( Juice Plus [ JP ] ) along with a complex supplement providing nutritional antioxidants and various herbal extracts ( Vineyard [ V ] ) , JP alone , or a matching placebo . At three and four weeks , BART was repeated both before and after the high-fat meal . Serum nitrate/nitrite concentrations were measured at baseline and at four weeks . RESULTS Four weeks of the JP-V combination blunted the detrimental effect of the high-fat meal ( -47.5 + /- 23.4 % at baseline vs. -1.7 + /- 9.7 % at four weeks [ p < 0.05 ] ) . Four weeks of JP alone had a similar beneficial effect ( -45.1 + /- 19.7 % at baseline vs. -16.6 + /- 10.3 % at four weeks [ p < 0.05 ] ) , whereas there was no substantial effect of the placebo . In the subjects treated with supplements , concentrations of serum nitrate/nitrite increased from 78 + /- 39 to 114 + /- 62 microm/l ( p < 0.02 ) . CONCLUSIONS Daily ingestion of modest amounts of a fruit/vegetable juice concentrate with or without adjunctive phytonutrient supplementation can reduce the immediate adverse impact of high-fat meals on flow-mediated vasoactivity and increase nitrate/nitrite blood concentration Chronic inflammation contributes to an increased risk for developing chronic conditions such as cardiovascular disease , diabetes , and cancer . A high " inflammatory load " is defined as elevated inflammation markers in blood or other tissues . We evaluated several markers of systemic inflammation from healthy adults and tested the hypothesis that two formulations of encapsulated fruit and vegetable juice powder concentrate with added berry powders ( FVB ) or without ( FV ) could impact markers of inflammatory load . Using a double-blind , placebo-controlled approach , 117 subjects were r and omly assigned to receive placebo , FV , or FVB capsules . Blood was drawn at baseline and after 60 d of capsule consumption . We measured inflammatory markers ( high sensitivity C-Reactive Protein , Monocyte Chemotactic Protein-1 , Macrophage Inflammatory Protein 1-β , and Regulated upon Activation , Normal T cell Expressed and Secreted ) , superoxide dismutase , and micronutrients ( β-carotene , vitamin C , and vitamin E ) . Results showed Monocyte Chemotactic Protein-1 , Macrophage Inflammatory Protein 1-β , and RANTES levels were significantly reduced and superoxide dismutase and micronutrient levels were significantly increased in subjects consuming both FV and FVB , relative to placebo . Data suggest a potential health benefit by consuming either formulation of the encapsulated juice concentrates through their anti-inflammatory properties BACKGROUND Studies of fruit and vegetable consumption in relation to overall health are limited . We evaluated the relationship between fruit and vegetable intake and the incidence of cardiovascular disease and cancer and of deaths from other causes in two prospect i ve cohorts . METHODS A total of 71 910 female participants in the Nurses ' Health study and 37,725 male participants in the Health Professionals ' Follow-up Study who were free of major chronic disease completed baseline semiquantitative food-frequency question naires in 1984 and 198 Output:	Overall , daily consumption of FV supplements significantly increased serum concentrations of the major antioxidant provitamins and vitamins found in plant foods ( β-carotene , vitamins C and E ) and folate . Functional changes , such as reduced serum homocysteine and markers of protein , lipid , and DNA oxidation , were also reported ; in addition , the health advantages on markers of inflammation , immunity , and endothelial function are promising . Key teaching points : Mixed fruit and vegetable supplements produced from plant foods may serve as an efficacious complement to the habitual diet in individuals who have suboptimal intake or variety of nutrient-dense fruits and vegetables . Current research indicates that fruit and vegetable concentrates significantly increase serum levels of antioxidant provitamins and vitamins ( β-carotene , vitamins C and E ) and folate and reduce homocysteine and markers of oxidative stress .
MS22135	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objective . To examine the effects of yoga versus an educational film program on sleep , mood , perceived stress , and sympathetic activation in older women with RLS . Methods . Participants were drawn from a larger trial regarding the effects of yoga on cardiovascular disease risk profiles in overweight , sedentary postmenopausal women . Seventy-five women were r and omized to receive either an 8-week yoga ( n = 38 ) or educational film ( n = 37 ) program . All 75 participants completed an RLS screening question naire . The 20 women who met all four diagnostic criteria for RLS ( n = 10 yoga , 10 film group ) comprised the population for this nested study . Main outcomes assessed pre- and post-treatment included : sleep ( Pittsburgh Sleep Quality Index ) , stress ( Perceived Stress Scale ) , mood ( Profile of Mood States , State-Trait Anxiety Inventory ) , blood pressure , and heart rate . Results . The yoga group demonstrated significantly greater improvements than controls in multiple domains of sleep quality and mood , and significantly greater reductions in insomnia prevalence , anxiety , perceived stress , and blood pressure ( all P's≤0.05 ) . Adjusted intergroup effect sizes for psychosocial variables were large , ranging from 1.9 for state anxiety to 2.6 for sleep quality . Conclusions . These preliminary findings suggest yoga may offer an effective intervention for improving sleep , mood , perceived stress , and blood pressure in older women with RLS Objectives : Fibromyalgia ( FM ) is a syndrome characterized by severe pain , fatigue and sleep disturbance . There is evidence of central hyper-responsiveness to sensory stimulation and impaired cardiovascular autonomic control . Laboratory investigations suggest that mindfulness-based stress reduction ( MBSR ) may improve autonomic functioning in FM . However , these findings may not reflect what occurs during naturalistic conditions , and MBSR studies during real-life functioning are lacking . We conducted a r and omized controlled , 3-armed study with 168 female FM patients . This report describes cardiac , respiratory , and physical activity findings . Methods : Eight-week MBSR was compared with wait-list and active control intervention . Ambulatory accelerometry and cardiorespiratory function were monitored over 24-h periods at 3 time points : preintervention , postintervention , and at the 8-week follow-up . Also , baseline levels were compared with an age-matched group of 33 healthy women . Findings : Activity heart rate , respiratory sinus arrhythmia , and ventilation were measured . Comparison with controls confirmed differences in cardiac autonomic tone and activity pattern among patients . Most measures also showed effects of time of day and point of measurement . Regarding the intervention study , there were no effects of treatment . In addition , there were no relations between patient-reported clinical improvement and objective physiological or accelerometry parameters . Intervention-related benefits in wellbeing were not associated with changes in daytime cardiorespiratory measures or pattern of physical activity . Conclusions : MBSR did not produce cardiac autonomic benefits or changes in daily activity in FM . Furthermore , the lack of an association between patient-experienced clinical improvement and objective physiological measures suggests that subjective changes in the wellbeing of FM patients over time are not related to alterations in the cardiorespiratory autonomic function or activity levels OBJECTIVE This study aim ed to develop and test a novel mindfulness-based intervention ( MBI ) design ed to control weight after bariatric surgery . DESIGN R and omized , controlled pilot trial . SETTING Beth Israel Deaconess Medical Center , Boston , MA , USA . INTERVENTIONS Bariatric patients 1 - 5 years post-surgery ( n=18 ) were r and omized to receive a 10-week MBI or a st and ard intervention . MAIN OUTCOME MEASURES Primary outcomes were feasibility and acceptability of the MBI . Secondary outcomes included changes in weight , eating behaviors , psychosocial outcomes , and metabolic and inflammatory biomarkers . Qualitative exit interviews were conducted post-intervention . Major themes were coded and extracted . RESULTS Attendance was excellent ( 6 of 9 patients attended ≥7 of 10 classes ) . Patients reported high satisfaction and overall benefit of the MBI . The intervention was effective in reducing emotional eating at 6 months ( -4.9±13.7 in mindfulness vs. 6.2±28.4 in st and ard , p for between-group difference=0.03 ) but not weight . We also observed a significant increase in HbA1C ( 0.34±0.38 vs. -0.06±0.31 , p=0.03 ) . Objective measures suggested trends of an increase in perceived stress and symptoms of depression , although patients reported reduced stress reactivity , improved eating behaviors , and a desire for continued mindfulness-based support in qualitative interviews . CONCLUSIONS This novel mindfulness-based approach is highly acceptable to bariatric patients post-surgery and may be effective for reducing emotional eating , although it did not improve weight or glycemic control in the short term . Longer-term studies of mindfulness-based approaches may be warranted in this population . CLINICAL TRIAL REGISTRATION Clinical Trials.gov identifier NCT02603601 We have developed a low dose Mindfulness-Based Intervention ( MBI-ld ) that reduces the time committed to meetings and formal mindfulness practice , while conducting the sessions during the workday . This reduced the barriers commonly mentioned for non-participation in mindfulness programs . In a controlled r and omized trial we studied university faculty and staff ( n=186 ) who were found to have an elevated CRP level,>3.0 mg/ml , and who either had , or were at risk for cardiovascular disease . This study was design ed to evaluate if MBI-ld could produce a greater decrease in CRP , IL-6 and cortisol than an active control group receiving a lifestyle education program when measured at the end of the 2 month interventions . We found that MBI-ld significantly enhanced mindfulness by 2-months and it was maintained for up to a year when compared to the education control . No significant changes were noted between interventions in cortisol , IL-6 levels or self-reported measures of perceived stress , depression and sleep quality at 2-months . Although not statistically significant ( p=.08 ) , the CRP level at 2-months was one mg/ml lower in the MBI-ld group than in the education control group , a change which may have clinical significance ( Ridker et al. , 2000 ; Wassel et al. , 2010 ) . A larger MBI-ld effect on CRP ( as compared to control ) occurred among participants who had a baseline BMI < 30 ( -2.67 mg/ml ) than for those with BMI > 30 ( -0.18 mg/ml ) . We conclude that MBI-ld should be more fully investigated as a low-cost self-directed complementary strategy for decreasing inflammation , and it seems most promising for non-obese subjects BACKGROUND Despite recent advances in pharmacologic and device therapy , morbidity and mortality from heart failure ( HF ) remain high . Yoga combines physical and breathing exercises that may benefit patients with HF . We hypothesized that an 8-week regimen of yoga in addition to st and ard medical therapy would improve exercise capacity , inflammatory markers , and quality of life ( QoL ) in patients with HF . METHODS AND RESULTS New York Heart Association Class I-III HF patients were r and omized to yoga treatment ( YT ) or st and ard medical therapy ( MT ) . Measurements included a grade d exercise test ( GXT ) to V O(2Peak ) and the following serum biomarkers : interleukin-6 ( IL-6 ) , high-sensitivity C-reactive protein ( hsCRP ) , and extracellular superoxide dismutase ( EC-SOD ) . The Minnesota Living with Heart Failure Question naire ( MLHFQ ) was administered to assess changes in QoL. A total of 19 patients were enrolled after the initial screening . Of the 19 patients , 9 were r and omized to YT and 10 to MT . Patients had a mean EF of 25 % . GXT time and V O(2Peak ) were significantly improved in the YT versus MT groups ( + 18 % in the YT and -7.5 % in MT ; P = .03 vs. control and + 17 in YT and -7.1 in MT ; P = .02 , respectively ) . There were statistically significant reductions in serum levels of IL-6 and hsCRP and an increase in EC-SOD in the YT group ( all P < .005 vs. MT ) . MLHFQ scores improved by 25.7 % in the YT group and by 2.9 % in the MT group . CONCLUSIONS Yoga improved exercise tolerance and positively affected levels of inflammatory markers in patients with HF , and there was also a trend toward improvements in This study reports the physiologic effects of up to 14 months of aerobic exercise in 101 older ( greater than 60 years ) men and women . After an extensive baseline physiologic assessment ( Time 1 ) , in which aerobic capacity and blood lipids were measured , subjects were r and omized to an aerobic exercise condition ( cycle ergometry , 3 times per week for 1 hour ) , nonaerobic yoga ( 2 times per week for 1 hour ) , or a waiting list nonexercise control group for 4 months , and then underwent a second ( Time 2 ) assessment . At the completion of the second assessment , all remaining subjects completed 4 months of aerobic exercise and were reevaluated ( Time 3 ) . Subjects were given the option of participating in 6 additional months of supervised aerobic exercise , and all available subjects completed a fourth assessment ( Time 4 ) 14 months after their initial baseline evaluation . Results indicated that subjects generally exhibited a 10 to 15 % improvement in peak oxygen consumption after 4 months of aerobic exercise training , and a 1 to 6 % improvement in aerobic power with additional aerobic exercise training . On the other h and , subjects , especially men , continued to have improvements in submaximal exercise performance ( i.e. , anaerobic threshold ) . In addition , aerobic exercise was associated with an improved lipid profile ; subjects participating in aerobic exercise for up to 14 months exhibited increased levels of high-density lipoprotein cholesterol . Maintenance of regular aerobic exercise for an extended time interval is associated with greater cardiovascular benefits among older adults than has been reported previously PURPOSE To compare the efficacy of the following two empirically supported group interventions to help distressed survivors of breast cancer cope : mindfulness-based cancer recovery ( MBCR ) and supportive-expressive group therapy ( SET ) . PATIENTS AND METHODS This multisite , r and omized controlled trial assigned 271 distressed survivors of stage I to III breast cancer to MBCR , SET , or a 1-day stress management control condition . MBCR focused on training in mindfulness meditation and gentle yoga , whereas SET focused on emotional expression and group support . Both intervention groups included 18 hours of professional contact . Measures were collected at baseline and after intervention by assessors blind to study condition . Primary outcome measures were mood and diurnal salivary cortisol slopes . Secondary outcomes were stress symptoms , quality of life , and social support . RESULTS Using linear mixed-effects models , in intent-to-treat analyses , cortisol slopes were maintained over time in both SET ( P = .002 ) and MBCR ( P = .011 ) groups relative to the control group , whose cortisol slopes became flatter . Women in MBCR improved more over time on stress symptoms compared with women in both the SET ( P = .009 ) and control ( P = .024 ) groups . Per- protocol analyses showed greater improvements in the MBCR group in quality of life compared with the control group ( P = .005 ) and in social support compared with the SET group ( P = .012 ) . CONCLUSION In the largest trial to date , MBCR was superior for improving stress levels , quality of life and social support [ CORRECTED ] for distressed survivors of breast cancer . Both SET and MBCR also result ed in more normative diurnal cortisol profiles than the control condition . The clinical implication s of this finding require further investigation Complementary medicine advocates the use of a multifactorial approach to address the varied aspects of hypertension . The aim of this study was to compare the blood pressure ( BP ) effect and medication use of a novel Comprehensive Approach to Lowering Measured Blood Pressure ( CALM-BP ) , based on complementary medicine principles , with the st and ard recommended Dietary Approach to Stop Hypertension ( DASH ) . A total of 113 patients treated with antihypertensive drugs were r and omly assigned to either CALM-BP treatment ( consisting of rice diet , walks , yoga , relaxation and stress management ) or to a DASH+exercise control group ( consisting of DASH and walks ) . Ambulatory 24-h and home BP were monitored over a 16-week programme , followed by 6 months of maintenance period . Medications were reduced if systolic BP dropped below 110 mm Hg accompanied by symptoms . In addition to BP reduction , medications were reduced because of symptomatic hypotension in 70.7 % of the CALM-BP group compared with 32.7 % in the DASH group , P<0.0001 . After 6 months , medication status was not altered in the majority of individuals . Significant reductions in body mass index , cholesterol and improved quality -of-life scores were observed only in the CALM-BP group . Lifestyle and diet modifications based on complementary medicine principles are highly effective with respect to BP control , medication use and cardiovascular risk factors In this study , a stress management program based on cognitive behavioural therapy principles was compared Output:	Interventions that included yoga asanas were associated with reduced evening cortisol , waking cortisol , ambulatory systolic blood pressure , resting heart rate , high frequency heart rate variability , fasting blood glucose , cholesterol and low density lipoprotein , compared to active control . Practice s that include yoga asanas appear to be associated with improved regulation of the sympathetic nervous system and hypothalamic-pituitary-adrenal system in various population
MS22136	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE : To compare adherence data from an electronic medication-event monitoring device ( MEMS , Aprex ) with pill counts in assisting pharmacists in making recommendations regarding diabetes therapy . DESIGN : Two-month , double-blind , r and omized , controlled trial . SETTING : Veterans Affairs Medical Center ambulatory care clinics . PATIENTS : Forty-seven patients with poor to fair metabolic control of diabetes mellitus were enrolled . Patients were excluded if they were receiving insulin , had a concurrent infection , required child-resistant caps or medication reminder devices , or could not return for follow-up visits . Twenty patients were r and omized to the MEMS and 27 to the control group ( pill counts ) . Fasting plasma glucose concentrations were measured monthly and glycohemoglobin concentrations were measured at baseline and 60 days . Thirty-two patients were evaluable : 15 using MEMS and 17 using pill counts . INTERVENTION : Investigators made pharmacologic or educational recommendations to the patient 's healthcare provider based on both laboratory data and MEMS readings in the treatment group or laboratory data and pill counts in the control group . MAIN OUTCOME MEASURE : Quantities and types of recommendations regarding diabetes therapy made by pharmacists using adherence data from the two methods were tabulated . RESULTS : In the MEMS group , 47 percent of the recommendations related to patient education compared with 12 percent in the control group ( p=0.028 ) . MEMS data would have changed four recommendations in the control group to involve patient education . CONCLUSIONS : MEMS data result ed in different numbers and types of recommendations than pill counts . Pharmacists then could make specific recommendations regarding patient education before resorting to pharmacologic manipulations This study examined the role of a Medication Event Monitoring System ( MEMS ) to assess pill-taking behavior and enhance compliance within a r and omized trial of bupropion-SR for smoking cessation . Female participants ( N = 97 ) received MEMS bottles containing bupropion-SR 150 mg or placebo , to be taken twice daily . A r and omly selected “ feedback ” group of participants was told about the recording device in the bottle cap and received weekly graphic feedback showing their pill-taking behavior with specific instructions for improving compliance . A “ no-feedback ” group was not informed about the MEMS bottles , and did not receive further instruction or feedback beyond the st and ard dosing instructions . Compliance outcomes were the total doses taken and number of doses taken within the prescribed time interval . Results indicated significantly higher compliance over time for the feedback group . Participation in the feedback group predicted higher compliance beyond demographic , smoking , and health belief variables , suggesting significant benefit in providing brief feedback and instruction throughout the medication regimen Objective The goal of this study was to evaluate clinical ly the acceptability of the IDAS II ( Intelligent Drug Administration System ) , a new electronic device that enables drug adherence monitoring . Methods IDAS II was compared to another electronic monitor , the Medication Event Monitoring System ( MEMS ) in a r and omised two-way cross-over study involving 24 hypertensive patients treated with irbesartan . Patients used each device for 2 months . The main parameter of evaluation was the patients ’ opinion on both devices . Rates of adherence and blood pressure were also assessed . Results Most patients considered both devices to be reliable reminders ( IDAS II : 75%;MEMS : 84 % , p = ns ) . Ten patients ( 42 % ) preferred the MEMS , while 11 ( 46 % ) preferred the IDAS II ; three ( 12 % ) expressed no preference . Patients found the MEMS device easier to use than the IDAS device ( p < 0.001 ) but appreciated the IDAS blister packs better than the MEMS bulk packaging ( p < 0.01 ) . Over the 4-month period , the median “ taking adherence ” was excellent ( 99.2 % ) and comparable with both devices . However , the regularity of drug intake timing was higher with the IDAS II ( p < 0.01 ) . Conclusion IDAS II , a new electronic device enabling drug adherence monitoring without reconditioning of the drugs appears to be a well-accepted device . Overall , practicability and acceptability of the IDAS II and the MEMS device were similar . Thus , IDAS II could be a useful tool for the management of long-term therapies Background and Objectives : Older adults ' adherence to antihypertensive medications is far lower than what is considered necessary for clinical effectiveness , despite the risks for adverse cardiovascular events from uncontrolled blood pressure ( BP ) in the elderly . This pilot study tested a novel 8-week behavioral feedback intervention to improve antihypertensive medication adherence ( MA ) and BP control among older adults on existing treatment for hypertension . Methods : Adults 60 years old , or older taking at least 1 antihypertensive medication were r and omized to receive the nurse-delivered adherence intervention or usual care . Medication adherence was monitored continuously using electronic monitoring for 20 weeks . Intervention-group participants received biweekly MA and BP feedback , habit counseling , medication and disease education , a medication instruction card , and were given an electronic medication bottle cap with a digital display that provided daily adherence feedback during the 8-week intervention . Blood pressure was measured by a nurse at 12 and 20 weeks after r and omization . Adherence and BP outcomes were described using descriptive statistics and analyzed for between- and within-group differences using Mann-Whitney U tests . Results : Fifteen participants ( median age , 71 years ; 73 % female ) were eligible for r and omization . Participants took an average of 5.8 prescription medications and 2.93 over-the-counter medications per day . A nonsignificant difference was noted in baseline MA between groups . At the end of the intervention , the treatment group had better antihypertensive MA than did the control group ( median MA : 100 % vs 27.3 % , U = 5.00 , P = .013 ) . Systolic BP improved slightly in the intervention group during the study and was significantly different at week 12 ( median systolic BP : 130 vs 152 mm Hg ; U = 4.50 , P = .008 ) . Diastolic BP was largely unchanged over the course of the study . Conclusion : The results indicate that the intervention had a positive effect on MA . Additional testing is needed to further evaluate the intervention and its effect on adherence behavior and BP control Background Innovative approaches are needed to support patients ' adherence to drug therapy . The Real Time Medication Monitoring ( RTMM ) system offers real time monitoring of patients ' medication use combined with short message service ( SMS ) reminders if patients forget to take their medication . This combination of monitoring and tailored reminders provides opportunities to improve adherence . This article describes the design of an intervention study aim ed at evaluating the effect of RTMM on adherence to oral antidiabetics . Methods / Design R and omised Controlled Trial ( RCT ) with two intervention arms and one control arm involving diabetes type 2 patients with suboptimal levels of adherence to oral antidiabetics ( less than 80 % based on pharmacy refill data ) . Patients in the first intervention arm use RTMM including SMS reminders and a personal webpage where they can monitor their medication use . Patients in the second intervention arm use RTMM without SMS reminders or webpage access . Patients in the control arm are not exposed to any intervention . Patients are r and omly assigned to one of the three arms . The intervention lasts for six months . Pharmacy refill data of all patients are available from 11 months before , until 11 months after the start of the intervention . Primary outcome measure is adherence to oral antidiabetics calculated from : 1 ) data collected with RTMM , as a percentage of medication taken as prescribed , and as percentage of medication taken within the correct time interval , 2 ) refill data , taking the number of days for which oral antidiabetics are dispensed during the study period divided by the total number of days of the study period . Differences in adherence between the intervention groups and control group are studied using refill data . Differences in adherence between the two intervention groups are studied using RTMM data . Discussion The intervention described in this article consists of providing RTMM to patients with suboptimal adherence levels . This system combines real time monitoring of medication use with SMS reminders if medication is forgotten . If RTMM proves to be effective , it can be considered for use in various patient population s to support patients with their medication use and improve their adherence . Trial registration Netherl and s Trial Register Russell C , Conn V , Ashbaugh C , Madsen R , Wakefield M , Webb A , Coffey D , Peace L. Taking immunosuppressive medications effectively ( TIMELink ) : a pilot r and omized controlled trial in adult kidney transplant recipients . Clin Transplant 2011 : 25 : 864–870 . © 2010 John Wiley & Sons This pilot study aim ed to examine the effectiveness of visual-feedback therapy for individuals with psychotic disorders . Visual-feedback therapy combines structured psychodynamic therapy and visual feedback achieved via an electronic monitoring medication cap to increase insight about medication behaviours . Thirty subjects were r and omly assigned either to visual feedback or to a supportive counselling group . Medication adherence was measured by both electronic monitoring and blood plasma drug concentration levels . The results showed that , at the end of the 3-month , intervention ( bimonthly sessions ) , adherence rates of the visual-feedback group slightly increased , but declined during the course of the study for the supportive counselling control group ( P=0.026 ) Background / Aims . One of the causes of uncontrolled secondary hyperparathyroidism ( sHPT ) is patient 's poor drug adherence . We evaluated the clinical benefits of an integrated care approach on the control of sHPT by cinacalcet . Methods . Prospect i ve , r and omized , controlled , multicenter , open-label study . Fifty hemodialysis patients on a stable dose of cinacalcet were r and omized to an integrated care approach ( IC ) or usual care approach ( UC ) . In the IC group , cinacalcet adherence was monitored using an electronic system . Results were discussed with the patients in motivational interviews , and drug prescription adapted accordingly . In the UC group , drug adherence was monitored , but results were not available . Results . At six months , 84 % of patients in the IC group achieved recommended iPTH targets versus 55 % in the UC group ( P = 0.04 ) . The mean cinacalcet taking adherence improved by 10.8 % in the IC group and declined by 5.3 % in the UC group ( P = 0.02 ) . Concomitantly , the mean dose of cinacalcet was reduced by 7.2 mg/day in the IC group and increased by 6.4 mg/day in the UC group ( P = 0.03 ) . Conclusions . The use of a drug adherence monitoring program in the management of sHPT in hemodialysis patients receiving cinacalcet improves drug adherence and iPTH control and allows a reduction in the dose of cinacalcet PURPOSE To investigate the impact of an intervention program to improve adherence with topical , once daily therapy for glaucoma . DESIGN R and omized controlled clinical trial . PARTICIPANTS Sixty-six patients with glaucoma being treated with a prostagl and in analog in 1 or both eyes at the Scheie Eye Institute or Wilmer Eye Institute between November 2006 and June 2007 . METHODS In an observational study , participants who took 75 % or fewer doses ( as measured using the travoprost Dosing Aid [ DA ] ) during an initial 3-month period were r and omized into 2 groups . The intervention group watched an educational video , review ed current barriers to drop-taking and possible solutions with a study coordinator , received regular phone call reminders , and had audible and visible reminders activated on their DA devices . The control group was told to take drops as prescribed and received no additional intervention . MAIN OUTCOME MEASURES Change in drop use adherence as determined by the DA device . RESULTS In the 3-month observation period before r and omization , intervention group patients had used a mean of 54+/-17 % of scheduled doses , and this increased to 73+/-22 % during the following 3-month period ( P<0.001 , n = 35 ) . The control mean adherence rate of 46+/-23 % at baseline was statistically unchanged during the follow-up observation period ( 51+/-30 % , P = 0.16 , n = 31 ) . In a multivariate analysis , intervention , baseline compliance rate of < 50 % , and white ethnicity were predictors of improved adherence during the 3 months of intervention . The intraocular pressure ( IOP ) of the intervention and control groups did not change between months 3 and 6 after intervention ( P = 0.96 , 0.34 , respectively ) , and there was no correlation of IOP change with adherence rate change between both groups ( Pearson correlation r = 0.06 , P = 0.51 ) . CONCLUSIONS A multifaceted intervention significantly increased adherence with glaucoma medications . Those with improved adherence were in the intervention group , had very low adherence rates at baseline , and were white . IOP did not correlate with adherence . Further research is needed to determine which components of this intervention were most effective A two-group r and omized experimental design was employed to assess the effects of monitoring and feedback on the compliance of 93 psychiatric out patients treated with lithium . Compliance in both groups was measured using self-report , lithium level , appointment-keeping , and medication refill frequency . The experimental group was also monitored using a unique electronic device Output:	Devices integrated into the care delivery system and design ed to record dosing events are most frequently associated with improved adherence , compared with other devices .
MS22137	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVES The aim of this study was to determine the diagnostic performance of a new method for quantifying fractional flow reserve ( FFR ) with computational fluid dynamics ( CFD ) applied to coronary computed tomography angiography ( CCTA ) data in patients with suspected or known coronary artery disease ( CAD ) . BACKGROUND Measurement of FFR during invasive coronary angiography is the gold st and ard for identifying coronary artery lesions that cause ischemia and improves clinical decision-making for revascularization . Computation of FFR from CCTA data ( FFR(CT ) ) provides a noninvasive method for identifying ischemia-causing stenosis ; however , the diagnostic performance of this new method is unknown . METHODS Computation of FFR from CCTA data was performed on 159 vessels in 103 patients undergoing CCTA , invasive coronary angiography , and FFR . Independent core laboratories determined FFR(CT ) and CAD stenosis severity by CCTA . Ischemia was defined by an FFR(CT ) and FFR ≤0.80 , and anatomically obstructive CAD was defined as a CCTA with stenosis ≥50 % . Diagnostic performance of FFR(CT ) and CCTA stenosis was assessed with invasive FFR as the reference st and ard . RESULTS Fifty-six percent of patients had ≥1 vessel with FFR ≤0.80 . On a per-vessel basis , the accuracy , sensitivity , specificity , positive predictive value , and negative predictive value were 84.3 % , 87.9 % , 82.2 % , 73.9 % , 92.2 % , respectively , for FFR(CT ) and were 58.5 % , 91.4 % , 39.6 % , 46.5 % , 88.9 % , respectively , for CCTA stenosis . The area under the receiver-operator characteristics curve was 0.90 for FFR(CT ) and 0.75 for CCTA ( p = 0.001 ) . The FFR(CT ) and FFR were well correlated ( r = 0.717 , p < 0.001 ) with a slight underestimation by FFR(CT ) ( 0.022 ± 0.116 , p = 0.016 ) . CONCLUSIONS Noninvasive FFR derived from CCTA is a novel method with high diagnostic performance for the detection and exclusion of coronary lesions that cause ischemia STUDY OBJECTIVE Coronary computed tomographic ( CT ) angiography has excellent performance characteristics relative to coronary angiography and exercise or pharmacologic stress testing . We hypothesize that coronary CT angiography can identify a cohort of emergency department ( ED ) patients with a potential acute coronary syndrome who can be safely discharged with a less than 1 % risk of 30-day cardiovascular death or nonfatal myocardial infa rct ion . METHODS We conducted a prospect i ve cohort study at an urban university hospital ED that enrolled consecutive patients with potential acute coronary syndromes and a low TIMI risk score who presented to the ED with symptoms suggestive of a potential acute coronary syndrome and received a coronary CT angiography . Our intervention was either immediate coronary CT angiography in the ED or after a 9- to 12-hour observation period that included cardiac marker determinations , depending on time of day . The main clinical outcome was 30-day cardiovascular death or nonfatal myocardial infa rct ion . RESULTS Five hundred sixty-eight patients with potential acute coronary syndrome were evaluated : 285 of these received coronary CT angiography immediately in the ED and 283 received coronary CT angiography after a brief observation period . Four hundred seventy-six ( 84 % ) were discharged home after coronary CT angiography . During the 30-day follow-up period , no patients died of a cardiovascular event ( 0 % ; 95 % confidence interval [ CI ] 0 % to 0.8 % ) or sustained a nonfatal myocardial infa rct ion ( 0 % ; 95 % CI 0 to 0.8 % ) . CONCLUSION ED patients with symptoms concerning for a potential acute coronary syndrome with a low TIMI risk score and a nonischemic initial ECG result can be safely discharged home after a negative coronary CT angiography test result BACKGROUND Multidetector computed tomography ( MDCT ) has high diagnostic value for detecting or excluding coronary artery stenosis . We examined performance characteristics of MDCT for diagnosing or excluding an acute coronary syndrome in patients presenting to the emergency department ( ED ) with possible ischemic chest pain and examined relation to clinical outcome during a 15-month follow-up period . METHODS AND RESULTS We prospect ively studied 58 patients ( 56+/-10 years of age , 36 % female ) with chest pain possibly ischemic in origin and no new ECG changes or elevated biomarkers . The patients underwent 64-slice contrast-enhanced MDCT , which showed normal coronary vessels ( no or trivial atheroma ) in 15 patients , nonobstructive plaque in 20 ( MDCT-negative patients ) , and obstructive coronary disease ( > or = 50 % luminal narrowing ) in 23 ( MDCT-positive group ) . By further investigation ( new elevation of cardiac biomarkers , abnormal myocardial perfusion scintigraphy and /or invasive angiography ) , acute coronary syndrome was diagnosed in 20 of the 23 MDCT-positive patients ( ED MDCT sensitivity 100 % [ 20/20 ] , specificity 92 % [ 35/38 ] , positive predictive value 87 % [ 20/23 ] , negative predictive value 100 % [ 35/35 ] ) . During a 15-month follow-up period , no deaths or myocardial infa rct ions occurred in the 35 patients discharged from the ED after initial triage and MDCT findings . One patient underwent late percutaneous coronary intervention ( late major adverse cardiovascular events rate , 2.8 % ) . Overall , ED MDCT sensitivity for predicting major adverse cardiovascular events ( death , myocardial infa rct ion , or revascularization ) during hospitalization and follow-up was 92 % ( 12/13 ) , specificity was 76 % ( 34/45 ) , positive predictive value was 52 % ( 12/23 ) , and negative predictive value was 97 % ( 34/35 ) . CONCLUSIONS We found that 64-slice cardiac MDCT is a potentially valuable diagnostic tool in ED patients with chest pain of uncertain origin , providing early direct noninvasive visualization of coronary anatomy . ED MDCT had high positive predictive value for diagnosing acute coronary syndrome , whereas a negative MDCT study predicted a low rate of major adverse cardiovascular events and favorable outcome during follow-up With the advent of multislice CT more than a decade ago , multislice CT angiography has demonstrated a huge potential in the less invasive imaging of cardiovascular disease , especially in the diagnosis of coronary artery disease . The diagnostic accuracy of multislice CT angiography has been significantly augmented with the rapid technical developments ranging from the initial 4-slice , to the current 64-slice and 256 and 320-slice CT scanners . This is mainly demonstrated by the improved spatial and temporal resolution when compared to the earlier type of CT scanners . Traditionally , multislice CT angiography is acquired with retrospective ECG-gating with acquisition of volume data at the expense of increased radiation dose , since data is acquired at the entire cardiac cycle , although not all of them are used for postprocessing or reconstructions . Recently , there is an increasing trend of utilising prospect i ve ECG-gating in cardiac imaging with latest multislice CT scanners ( 64 or more slices ) with significant reduction of radiation dose when compared to retrospective ECG-gating method . However , there is some debate as to the diagnostic value of prospect i ve ECG-gating in the diagnosis of coronary artery disease , despite its attractive ability to reduce radiation dose . This article will review the performance of retrospective ECG-gating in the diagnostic value of coronary artery disease , highlight the potential applications of prospect i ve ECG-gating , and explore the future directions of multislice CT angiography in cardiac imaging OBJECTIVES The goal of this study was to determine the diagnostic performance of noninvasive fractional flow reserve ( FFR ) derived from st and ard acquired coronary computed tomography angiography ( CTA ) data sets ( FFR(CT ) ) for the diagnosis of myocardial ischemia in patients with suspected stable coronary artery disease ( CAD ) . BACKGROUND FFR measured during invasive coronary angiography ( ICA ) is the gold st and ard for lesion-specific coronary revascularization decisions in patients with stable CAD . The potential for FFR(CT ) to noninvasively identify ischemia in patients with suspected CAD has not been sufficiently investigated . METHODS This prospect i ve multicenter trial included 254 patients scheduled to undergo clinical ly indicated ICA for suspected CAD . Coronary CTA was performed before ICA . Evaluation of stenosis ( > 50 % lumen reduction ) in coronary CTA was performed by local investigators and in ICA by an independent core laboratory . FFR(CT ) was calculated and interpreted in a blinded fashion by an independent core laboratory . Results were compared with invasively measured FFR , with ischemia defined as FFR(CT ) or FFR ≤0.80 . RESULTS The area under the receiver-operating characteristic curve for FFR(CT ) was 0.90 ( 95 % confidence interval [ CI ] : 0.87 to 0.94 ) versus 0.81 ( 95 % CI : 0.76 to 0.87 ) for coronary CTA ( p = 0.0008 ) . Per-patient sensitivity and specificity ( 95 % CI ) to identify myocardial ischemia were 86 % ( 95 % CI : 77 % to 92 % ) and 79 % ( 95 % CI : 72 % to 84 % ) for FFR(CT ) versus 94 % ( 86 to 97 ) and 34 % ( 95 % CI : 27 % to 41 % ) for coronary CTA , and 64 % ( 95 % CI : 53 % to 74 % ) and 83 % ( 95 % CI : 77 % to 88 % ) for ICA , respectively . In patients ( n = 235 ) with intermediate stenosis ( 95 % CI : 30 % to 70 % ) , the diagnostic accuracy of FFR(CT ) remained high . CONCLUSIONS FFR(CT ) provides high diagnostic accuracy and discrimination for the diagnosis of hemodynamically significant CAD with invasive FFR as the reference st and ard . When compared with anatomic testing by using coronary CTA , FFR(CT ) led to a marked increase in specificity . ( HeartFlowNXT-HeartFlow Analysis of Coronary Blood Flow Using Coronary CT Angiography [ HFNXT ] ; NCT01757678 ) OBJECTIVES We prospect ively studied the prognostic value of predischarge dobutamine stress echocardiography ( DSE ) in low-risk chest pain patients with a normal or nondiagnostic electrocardiogram ( ECG ) and a negative serial troponin T. BACKGROUND Noninvasive stress testing is recommended before discharge or within 72 h in patients with low-risk chest pain . The prognostic value of immediate DSE has not been studied in a blinded , prospect i ve fashion . METHODS Patients presenting at the emergency room within 6 h of symptom onset and a normal or nondiagnostic ECG were eligible . Dobutamine stress echocardiography was performed after unstable coronary artery disease was ruled out by a st and ard rule-out protocol and a negative serial troponin T ; the occurrence of any new wall motion abnormality was considered positive . Results were kept blinded . End points were cardiac death , myocardial infa rct ion , rehospitalization for unstable angina or revascularization . RESULTS In total , 377 patients were included . There were 2 deaths , 2 myocardial infa rct ions , 8 rehospitalization for unstable angina , and 10 revascularizations at six-month follow-up . The end points occurred in 8/26 ( 30.8 % ) patients with a positive versus 14/351 ( 4.0 % ) patients with a negative DSE ( odds ratio , 10.7 ; 95 % confidence interval , 4.0 to 28.8 ; p < 0.0001 ) . By multivariate analysis , DSE remained a predictor of end points ( p < 0.0001 ) . CONCLUSIONS A predischarge DSE had important , independent prognostic value in low-risk , troponin negative , chest pain patients Objectives To assess feasibility , image quality , and radiation dose of prospect ively ECG-triggered coronary CT angiography ( CTA ) in orthotopic heart transplant ( OHT ) recipients . Methods 47 consecutive OHT recipients ( 40 men , mean age 62.1±10.9 years , mean heart rate 86.3±14.4 bpm ) underwent dual- source CTA to rule out coronary allograft vasculopathy in a prospect ively ECG-triggered mode with data acquisition during 35 % to 45 % of the cardiac cycle . Two independent observers blindly assessed image quality on a per-segment and per-vessel basis using a four-point scale ( 1- Output:	Bivariate analysis revealed that CCTA had statistically greater sensitivity , specificity , PPV and overall diagnostic accuracy when compared to SE and SPECT . CONCLUSIONS All three modalities , when employed by an experienced clinician , are highly accurate . Each has its own strengths and limitations making each well suited for different patient groups . CCTA has higher accuracy than SE and SPECT , but it has many drawbacks , most importantly its lack of physiologic data
MS22138	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background : Tobacco smoking is an integral part of prison life and an established part of the culture . Little attention has been paid to prevention of smoking in prison . Approximately 70–80 % of prisoners have been identified as current smokers . Aim : To assess the effectiveness of smoking cessation intervention among male prisoners at Central Jail , Bangalore city . Aim : To assess the effectiveness of smoking cessation intervention among male prisoners at Central Jail , Bangalore city . Material s and Methods : A r and omized controlled trial was planned among male prisoners in Central Jail , Bangalore city . There were 1600 convicted prisoners . A self-administered question naire was given to the prisoners to assess their smoking behavior by which prevalence of tobacco smoking was found . Exactly 1352 tobacco users were studied . Among them , there were 1252 smokers . Based on inclusion criteria and informed consent given by the prisoners , a sample of 600 was chosen for the study by systematic r and om sampling . Among the 600 prisoners , 300 were r and omly selected for the study group and 300 for the control group . Results : Prevalence of tobacco smoking among the prisoners was 92.60 % . In the present study , after smoking cessation intervention , 17 % showed no change in smoking , 21.66 % reduced smoking , 16 % stopped smoking , and 45.33 % relapsed ( P < 0.0001 ) at the end of 6-month follow-up in the study group . Conclusion : Tobacco use was high among the prisoners . Tobacco reduction is possible in the prison even if the living conditions are not favorable . Relatively high rate of relapse in our study indicates that some policies should be adopted to improve smokers ’ information on consequences of tobacco on health and motivational intervention should be added to prisoners INTRODUCTION Tobacco use in low- to middle-income countries is a major public health concern for both smokers and those exposed to environmental tobacco smoke ( ETS ) . Egypt has made important strides in controlling tobacco use , but smoking and ETS remain highly prevalent . This r and omized intervention sought to improve the target population 's knowledge regarding the hazards of smoking and ETS and to change attitudes and smoking behaviors within the community and the household . METHODS In this 2005 - 2006 study in Egypt 's Qalyubia governorate , trained professionals visited schools , households , mosques , and health care centers in rural villages r and omly selected for the intervention to discuss the adverse effects of smoking and ETS exposure and ways to reduce one 's ETS exposure . Data collected in interviewer-facilitated surveys before and after the intervention period were analyzed in pairwise comparisons with data from control villages to assess the effectiveness of the intervention in achieving its aims . RESULTS The intervention group showed a greater increase in underst and ing the dangers associated with smoking cigarettes and waterpipes and became more proactive in limiting ETS exposure by asking smokers to stop , avoiding areas with ETS , and enacting smoking bans in the home . However , the intervention had little to no impact on the number of smokers and the amount of tobacco smoked . CONCLUSIONS Results are consistent with previous studies showing that changing smokers ' behavior can be difficult , but community-wide efforts to reduce ETS exposure through smoking bans , education , and empowering people to ask smokers to stop are effective . The method can be generalized to other setting BACKGROUND In India , tobacco consumption is responsible for one of the highest rates of oral cancer in the world , the annual oral cancer incidence is steadily increasing among young tobacco users . Studies have documented efforts taken by physicians , doctors and even dentists , in the form of individual or group counseling to curb tobacco use in smoke or smokeless form . However , which one is more effective , still remains an unanswered question . The aim of the study was to compare the effectiveness of individual and group counseling for cessation of the tobacco habit amongst industrial workers in Pune and to compare quit rates . MATERIAL S AND METHODS An interventional study design was selected for 150 industrial workers which were stratified r and omly into three groups ( control , individual and group counseling groups ) and interventions were provided to individual and group counseling groups over a period of six months , which were then compared with the control group that received brief intervention at the start of the study . RESULTS There was significant difference in the quit rates of the participants in the individual counseling group ( ICG ) and group counseling group ( GCG ) when compared at 6 months with the control counseling group ( CCG ) . In the individual counseling group was 6 % while in group counseling group it was 7.5 % after six months of counseling . CONCLUSIONS No conclusion could be drawn whether individual or group counseling were better interms of quit rates . Individual and group counseling groups were definitely better than the control group when compared at 3 and 6 months , respectively Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Background In response to India 's growing tobacco epidemic , strategies are needed to decrease tobacco use among Indian youth , particularly among those who are economically disadvantaged . The objective of this study was to assess the effectiveness of a school-based life-skills tobacco control program for youth of low socio-economic status in Mumbai and the surrounding state of Maharashtra . We hypothesized that compared to youth in control schools , youth exposed to the program would have greater knowledge of effects of tobacco use ; be more likely to take action to prevent others from using tobacco ; demonstrate more positive life skills and attitudes ; and be less likely to report tobacco use . Methods / Findings Using a quasi-experimental design , we assessed program effectiveness by comparing 8th and 9th grade students in intervention schools to 8th grade students in comparable schools that did not receive the program . Across all schools , 1851 students completed a survey that assessed core program components in early 2010 . The program consisted of activities focused on building awareness about the hazards of tobacco , developing life skills , and advocacy development . The primary outcome measure was self-reported tobacco use in the last 30 days . Findings indicate that 4.1 % of 8th grade intervention students ( OR = 0.51 ) and 3.6 % of 9th grade intervention students ( OR = 0.33 ) reported using tobacco at least once in the last 30 days , compared to 8.7 % of students in the control schools . Intervention group students were also significantly more knowledgeable about tobacco and related legislation , reported more efforts to prevent tobacco use among others , and reported stronger life skills and self-efficacy than students in control schools . Limitations to the study include schools not being r and omly assigned to condition and tobacco use being measured by self-report . Conclusions This program represents an effective model of school-based tobacco use prevention that low-income schools in India and other low- and middle-income countries can replicate BACKGROUND Cervical cancer is the leading cause of cancer mortality among women in India . Because Pap smear screening is not feasible in India , we need to develop effective alternatives . METHODS A cluster-r and omized controlled study was initiated in 1998 in Mumbai , India , to investigate the efficacy of visual inspection with acetic acid ( VIA ) performed by primary health workers in reducing cervical cancer mortality . Four rounds of cancer education and VIA screening were conducted at 24-month intervals in the screening group , whereas cancer education was offered once at entry to the control group . The study was planned for 16 years to include four screening rounds followed by four monitoring rounds . We present results after 12 years of follow-up . Poisson regression method was used to calculate the rate ratios ( RRs ) ; two-sided χ(2 ) was used to calculate the probability . RESULTS We recruited 75360 women from 10 clusters in the screening group and 76178 women from 10 comparable clusters in the control group . In the screening group , we achieved 89 % participation for screening and 79.4 % compliance for diagnosis confirmation . The incidence of invasive cervical cancer was 26.74 per 100000 ( 95 % confidence interval [ CI ] = 23.41 to 30.74 ) in the screening group and 27.49 per 100000 ( 95 % CI = 23.66 to 32.09 ) in the control group . Compliance to treatment for invasive cancer was 86.3 % in the screening group and 72.3 % in the control group . The screening group showed a statistically significant 31 % reduction in cervical cancer mortality ( RR = 0.69 ; 95 % CI = 0.54 to 0.88 ; P = .003 ) . CONCLUSIONS VIA screening by primary health workers statistically significantly reduced cervical cancer mortality . Our study demonstrates the efficacy of an easily implementable strategy that could prevent 22000 cervical cancer deaths in India and 72600 deaths in re source -poor countries annually Background India has the second largest diabetic population ( 61 million ) and tobacco users ( 275 million ) in the world . Data on smoking cessation among diabetic patients are limited in low and middle income countries . The objective of the study was to document the effectiveness of diabetic specific smoking cessation counseling by a non-doctor health professional in addition to a cessation advice to quit , delivered by doctors . Methods In our parallel-group r and omized controlled trial , we selected 224 adult diabetes patients aged 18 years or older who smoked in the last month , from two diabetes clinics in South India . Using a computer generated r and om sequence with block size four ; the patients were r and omized equally into intervention-1 and intervention-2 groups . Patients in both groups were asked and advised to quit smoking by a doctor and distributed diabetes specific education material s. The intervention-2 group received an additional diabetes specific 30 minutes counseling session using the 5As ( Ask , Advise , Assess , Assist and Arrange ) , and 5 Rs ( Relevance , Risks , Rewards , Roadblocks and Repetition ) from a non-doctor health professional . Follow up data were available for 87.5 % of patients at six months . The Quit Tobacco International Project is supported by a grant from the Fogarty International Centre of the US National Institutes of Health (RO1TW005969 - 01).The primary outcomes were quit rate ( seven day smoking abstinence ) and harm reduction ( reduction of the number of cigarettes / bidis smoked per day > 50 % of baseline use ) at six months . Results In the intention to treat analysis , the odds for quitting was 8.4 [ 95 % confidence interval ( CI ) : 4.1 - 17.1 ] for intervention-2 group compared to intervention-1 group . Even among high level smokers the odds of quitting was similar . The odds of harm reduction was 1.9 ( CI : 0.8 - 4.1 ) for intervention-2 group compared to intervention-1 group . Conclusions The value addition of culturally sensitive diabetic specific cessation counseling sessions delivered by non-doctor health professional was an impressive and efficacious way of preventing smoking related diabetic complications . Trial Registration Clinical Trial Registry of India ( CTRI/2012/01/002327 OBJECTIVES We assessed the effectiveness of a 2-year multicomponent , school-based intervention design ed to reduce tobacco use rates among adolescents in an urban area of India . METHODS Students from 32 schools in Delhi and Chennai , India , were recruited and r and omly assigned to an intervention or control group . Baseline , intermediate , and outcome data were collected from 2 cohorts of 6th- and 8th- grade students in 2004 ; 14,063 students took part in the study and completed a survey in 2004 , 2005 , or 2006 . The intervention consisted of behavioral classroom curricula , school posters , a parental involvement component , and peer-led activism . The main outcome measures were self-reported use of cigarettes , bidis ( small h and -rolled , often flavored , cigarettes ) , and chewing tobacco and future intentions to smoke or use chewing tobacco . RESULTS Findings showed that students in the intervention group were significantly less likely than were students in the control group to exhibit increases in cigarette smoking or bidi smoking over the 2-year study period . They were also less likely to intend to smoke or chew tobacco in the future . CONCLUSIONS School-based programs similar to the intervention examined here should be considered as part of a multi strategy approach to reducing tobacco use among young people in India BACKGROUND Prevalence of tobacco use is higher in the rural than urban areas of India . Unlike tobacco cessation clinics located in urban areas , community-based smoking cessation intervention has the potential to reach a wider section of the community to assist in smoking cessation in the rural setting . The present study aim ed to assess the effectiveness of a cessation intervention in rural Kerala state , India . MATERIAL S AND METHODS Current daily smoking resident males in the age group 18 - 60 years from four community development blocks in rural Kerala were r and omly allocated to intervention and control groups . The intervention group received multiple approaches in which priority was given to face-to-face interviews and telephone counselling . Initially educational material s on tobacco hazards were distributed . Further , four rounds of counselling sessions were conducted which included a group counselling with a medical camp as well as individual counselling by trained medical social workers . The control group received general awareness training Output:	There was supportive evidence that cervical screening and hepatitis B immunisation prevent cancer in LLMICs .
MS22139	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Study Design . Prospect i ve clinical study . Objective . To test whether elastic stabilization with the Dynesys system ( Zimmer Spine , Minneapolis , MN ) provides enough stability to prevent further progression of spondylolisthesis as well as instability after decompression for spinal stenosis with degenerative spondylolisthesis . Summary of Background Data . In spinal stenosis with degenerative spondylolisthesis , decompression and fusion is widely recommended . However , patients have donor site pain . In 1994 , a dynamic transpedicular system ( Dynesys ) was introduced to the market , stating that stabilization is possible without bone grafting . Methods . A total of 26 patients ( mean age 71 years ) with lumbar spinal stenosis and degenerative spondylolisthesis underwent interlaminar decompression and dynamic stabilization with the Dynesys system . Minimum follow-up was 2 years . Operative data , clinical outcome , and plain and flexion/extension radiographs were obtained and compared to preoperative and postoperative data . Results . Mean leg pain decreased significantly ( P < 0.01 ) , and mean walking distance improved significantly to more than 1000 m ( P < 0.01 ) . There were 5 patients ( 21 % ) who still had some claudication . A total of 21 patients ( 87.5 % ) would undergo the same procedure again . Radiographically , no significant progression of spondylolisthesis could be detected . The implant failure rate was 17 % , and none of them were clinical ly symptomatic . Conclusions . In elderly patients with spinal stenosis with degenerative spondylolisthesis , dynamic stabilization with the Dynesys system in addition to decompression leads to similar clinical results as seen in established protocol s using decompression and fusion with pedicle screws . It maintains enough stability to prevent further progression of spondylolisthesis or instability . With the Dynesys system , no bone grafting is necessary , therefore , donor site morbidity can be avoided Abstract . Various forms of lumbar instability require a surgical stabilization . As an alternative to fusion , a mobile , dynamic stabilization restricting segmental motion would be advantageous in various indications , allowing greater physiological function and reducing the inherent disadvantages of rigid instrumentation and fusion . The dynamic neutralization system for the spine ( Dynesys ) is a pedicle screw system for mobile stabilization , consisting of titanium alloy screws connected by an elastic synthetic compound , controlling motion in any plane ( non-fusion system ) . This prospect i ve , multi-center study evaluated the safety and efficacy of Dynesys in the treatment of lumbar instability conditions , evaluating pre- and post-operative pain , function , and radiological data on a consecutive series of 83 patients . Indications consisted of unstable segmental conditions , mainly combined with spinal stenosis ( 60.2 % ) and with degenerative discopathy ( 24.1 % ) , in some cases with disc herniation ( 8.4 % ) , and with revision surgery ( 6.0 % ) . Thirty-nine patients additionally had degenerative spondylolisthesis , and 30 patients had undergone previous lumbar surgery . In 56 patients instrumentation was combined with direct decompression . The mean age at operation was 58.2 ( range 26.8–85.3 ) years ; the mean follow-up time was 38.1 months ( range 11.2–79.1 months ) . There were nine complications unrelated to the implant , and one due to a screw malplacement . Four of them required an early surgical reintervention . Additional lumbar surgery in the follow-up period included : implant removal and conversion into spinal fusion with rigid instrumentation for persisting pain in three cases , laminectomy of an index segment in one case and screw removal due to loosening in one case . In seven cases , radiological signs of screw loosening were observed . In seven cases , adjacent segment degeneration necessitated further surgery . Mean pain and function scores improved significantly from baseline to follow-up , as follows : back pain scale from 7.4 to 3.1 , leg pain scale from 6.9 to 2.4 , and Oswestry Disability Index from 55.4 % to 22.9 % . These study results compare well with those obtained by conventional procedures ; in addition to which , mobile stabilization is less invasive than fusion . Long-term screw fixation is dependent on correct screw dimension and proper screw positioning . The natural course of polysegmental disease in some cases necessitates further surgery as the disease progresses . Dynamic neutralization proved to be a safe and effective alternative in the treatment of unstable lumbar conditions Controlled clinical trials of the treatment of acute myocardial infa rct ion offer a unique opportunity for the study of the potential influence on outcome of bias in treatment assignment . A group of 145 papers was divided into those in which the r and omization process was blinded ( 57 papers ) , those in which it may have been unblinded ( 45 papers ) , and those in which the controls were selected by a nonr and om process ( 43 papers ) . At least one prognostic variable was maldistributed ( P less than 0.05 ) in 14.0 per cent of the blinded-r and omization studies , in 26.7 per cent of the unblinded-r and omization studies , and in 58.1 per cent of the nonr and omized studies . Differences in case-fatality rates between treatment and control groups ( P less than 0.05 ) were found in 8.8 per cent of the blinded-r and omization studies , 24.4 per cent of the unblinded-r and omization studies , and 58.1 per cent of the nonr and omized studies . These data emphasize the importance of keeping those who recruit patients for clinical trials from suspecting which treatment will be assigned to the patient under consideration OBJECTIVES The aim of this study was to evaluate the outcome of wide surgical decompression and concomitant posterior instrumentation in patients with degenerative lumbar spinal stenosis . METHODS Thirty-seven consecutive patients ( 14 men , 23 women ; mean age 64 years ; range 36 to 82 years ) with degenerative lumbar spinal stenosis were prospect ively evaluated following surgical treatment with spinal decompression and concomitant instrumented posterior fusion . The mean duration of symptoms before surgery was 24 months ( range 12 to 60 months ) . Preoperatively , six patients had degenerative spondylolisthesis ( grade 1 ) and two patients had degenerative lumbar scoliosis . Decompression was performed at one level in four patients , at two levels in 16 patients , at three levels in 11 patients , and at four levels in six patients . Discectomy was also performed in seven patients . Preoperatively and postoperatively , the patients were assessed by the Oswestry Disability Index and a visual analog scale for overall pain ( leg and low back pain ) . The satisfaction level of the patients for surgical outcome was also question ed . The mean follow-up period was 4.6 years ( range 1 to 7 years ) . RESULTS Preoperatively , the mean Oswestry Disability Index score was 60.5 % and the mean overall pain score was 7.5 . Postoperatively , the Oswestry Disability Index score significantly decreased to 36.8 % and the overall pain score significantly decreased to 3.5 ( p<0.001 ) . Preoperative and postoperative walking distances of the patients were as follows , respectively : more than 1,000 meters ( 6 and 14 patients ) , 500 to 1,000 meters ( 5 and 7 patients ) , less than 500 meters ( 26 and 16 patients ) . Twenty patients did not use any analgesics and eight patients used analgesics on a weekly basis . Twenty-six patients were satisfied with the surgical outcome , nine patients were somewhat satisfied , and two patients were dissatisfied . Overall , the outcomes were excellent to good in 22 patients ( 59.5 % ) . None of the patients required revision surgery . CONCLUSION Most patients with degenerative lumbar spinal stenosis benefit from decompressive surgery . Patients with long-st and ing preoperative symptoms and concomitant diseases often have poor results and are less satisfied with the postoperative outcome Study Design . Prospect i ve comparative r and omized clinical and radiologic study . Objective . This study was conducted to compare the short-term effects of rigid versus semirigid and dynamic instrumentation on the global and segmental lumbar spine profile , subjective evaluation of the result , and the associated complications . Background Data . Lumbar spine fusion with rigid instrumentation for degenerative spinal disorders seems to increase the fusion rate . However , rigid instrumentation may be associated with some undesirable effects , such as increased low back pain following decrease of lumbar lordosis , fracture of the vertebral body and pedicle , pedicle screw loosening , and adjacent segment degeneration . The use of semirigid and dynamic devices has been advocated to reduce such adverse effects of the rigid instrumentation and thus to achieve a more physiologic bony fusion . Material s and Methods . This study compared 3 equal groups of 45 adult patients , who underwent primary decompression and stabilization for symptomatic degenerative lumbar spinal stenosis . The patients of each group were r and omly selected and received either the rigid ( Group A ) , or semirigid ( Group B ) , or dynamic ( Group C ) spinal instrumentation with formal decompression and fusion . The mean ages of the patients who received rigid , semirigid , and dynamic instrumentation were 65 ± 9 , 59 ± 16 , and 62 ± 10 years , respectively . All patients had detailed roentgenographic study including computed tomography scan and magnetic resonance imaging before surgery to the latest follow-up observation . The following roentgenographic parameters were measured and compared in all spines : lumbar lordosis ( L1–S1 ) , total lumbar lordosis ( T12–S1 ) , sacral tilt , distal lordosis ( L4–S1 ) , segmental lordosis , vertebral inclination , and disc index . The SF-36 health survey and Visual Analogue Scale was used before surgery to the latest evaluation . Results . All patients were evaluated after a mean follow-up of 47 ± 14 months . Both lumbar and total lordosis correction did not correlate with the number of the levels instrumented in any group . Total lordosis was slightly decreased after surgery ( 3 % , P < 0.05 ) in Group C. The segmental lordosis L2–L3 was increased after surgeryby8.5 % ( P < 0.05 ) in Group C , whereas the segmentallordosis L4–L5 was significantly decreased in Group A and C by 9.8 % ( P = 0.01 ) and 16.2 % ( P < 0.01 ) , respectively . The disc index L2–L3 was decreased after surgery in Group A and C by 17 % ( P < 0.05 ) and 23.5 % ( P < 0.05 ) , respectively . The disc index L3–L4 was increased in Group C by 18.74 % ( P < 0.01 ) . The disc index L4–L5 was after surgery decreased in all 3 groups : Group A by 21 % ( P = 0.01 ) , Group B by 13 % ( P < 0.05 ) , and Group C by 13.23 % ( P < 0.05 ) . The disc index L5–S1 was significantly decreased in Group B by 13 % ( P < 0.05 ) . The mean preoperative scores of the SF-36 before surgery were 11 , 14 , and 13 for Groups C , B , and A , respectively . In the first year after surgery , there was a significant increase of the preoperative SF-36 scores to 65 , 61 , and 61 for Groups C , B , and A , respectively , that represents an improvement of 83 % , 77 % , and 79 % , respectively . In the second year after surgery and thereafter , there was a further increase of SF-36 scores of 19 % , 23 % , and 21 % for Groups C , B , and A , respectively . The mean preoperative scores of Visual Analogue Scale for low back pain for Groups C , B , and A were 5 , 4.5 , and 4.3 , respectively , and decreased after surgery to 1.9 , 1.5 , and 1.6 , respectively . The mean preoperative scores of the Visual Analogue Scale for leg pain for Groups C , B , and A were 7.6 , 7.1 , and 6.9 , respectively , and decreased after surgery to 2.5 , 2.5 , and 2.7 , respectively . All fusions healed radiologically within the expected time in all three groups without pseudarthrosis or malunion . Delayed hardware failure ( 1 screw and 2 rod breakages ) 1 year and 18 months after surgery without radiologic pseudarthrosis was observed in 2 patients in Group C. Asymptomatic radiolucent areas were shown around pedicle screws in the pedicles L5 and S1 in 2 , 3 , and 4 cases in Group C , A , and B , respectively . There was no adjacent segment degeneration in any spine until the last evaluation . Discussion and Conclusion . This comparative study showed that all three instrumentations applied over a short area for symptomatic degenerative spinal stenosis almost equally after surgery maintained the preoperative global and segmental sagittal profile of the lumbosacral spine and was followed by similarly significant improvement of both self- assessment and pain scores . Hardware failure occurred at a low rate following dynamic instrumentation solely without radiologically visible pseudarthrosis or loss of correction . Because of the similar clinical and radiologic data in all three groups and the relative small number of patients that were included in each group , it is difficult for the authors to make any recommendation in favor of any instrumentation Output:	CONCLUSION It was not possible to reveal any evidence for benefits using DPF compared to rigid fixation in surgery for lumbar spine
MS22140	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: This study explored the equivalence of physical function assessment by physical therapists ( PTs ) during face-to-face and remote administration of the European Stroke Scale ( ESS ) and the Functional Reach Test ( FRT ) to 26 subjects with a history of stroke . Patients were r and omized to remote or face-to-face administration groups . Each patient was simultaneously rated by both the face-to-face and remote PTs . The PTs were blinded to each other 's results . Equivalence was set at the 95 % limits of agreement . When the face-to-face PT directed the patient , the two PTs reported equivalent values in more than 90 % of the patients for the FRT and for all ESS components , with the exception of gait ( 83 % ) and maintaining leg position ( 85 % ) . When the remote PT directed the patient , the two PTs reported equivalent values in more than 90 % of the patients for the FRT and more than 83 % for all ESS components . Televideo assessment of function by PTs is substantially equivalent to a face-to-face encounter BACKGROUND AND PURPOSE Telemedicine can disseminate vascular neurology expertise and optimize recombinant tissue plasminogen activator ( rt-PA ) use for acute ischemic stroke in rural underserved communities . The purpose of this study was to prospect ively assess whether telemedicine or telephone was superior for decision-making . METHODS The study design is a pooled analysis of two identically design ed r and omized controlled trials conducted in a multistate hub and spoke telestroke network setting with acute stroke syndrome patients , comparing telemedicine versus telephone-only consultations . From each trial , common data elements were pooled to assess , principally , for correctness of thrombolysis decision-making . Secondary outcomes included rt-PA use rate , 90-day functional outcome , post-thrombolysis intracranial hemorrhage , and data completeness . RESULTS Two hundred seventy-six pooled patients were evaluated . Correct thrombolysis eligibility decisions were made more often with telemedicine ( 96 % telemedicine , 83 % telephone ; odds ratio [ OR ] 4.2 ; 95 % confidence interval [ CI ] 1.69 - 10.46 ; p=0.002 ) . Intravenous rt-PA usage was 26 % ( 29 % telemedicine , 24 % telephone ; OR 1.27 ; 95 % CI 0.71 - 2.25 ; p=0.41 ) . Ninety-day outcomes were not different for Barthel Index , modified Rankin Scale , or mortality . There was no difference in post-thrombolysis intracranial hemorrhage ( 8 % telemedicine , 6 % telephone ; p>0.999 ) . CONCLUSIONS This pooled analysis supports the hypothesis that stroke telemedicine consultations , compared with telephone-only , result in more accurate decision-making . Together with high rt-PA utilization rate , low post-rt-PA intracranial hemorrhage rate , and acceptable patient outcome , the results confirm that telemedicine is a viable consultative tool for acute stroke . The replication of the hub and spoke network infrastructure supports the generalizability of telemedicine when used in broader setting We conducted a pilot telerehabilitation study with post-stroke patients with arm motor impairment . We compared the degree of satisfaction of patients undergoing a virtual reality ( VR ) therapy programme at home ( Tele-VR group ) to satisfaction experienced by those undergoing the same VR therapy in a hospital setting ( VR-group ) . The rehabilitation equipment used a 3D motion tracking system to create a virtual environment in which the patient 's movement was represented . In tele-therapy , the patient equipment was installed in their homes , connected to the hospital by four ISDN lines at a total b and width of 512 kbit/s . Rehabilitation data were transmitted via one line and videoconferencing via the other three . Ten patients with mild to intermediate arm motor impairment due to an ischaemic stroke , were r and omized into VR or Tele-VR groups . A question naire was used at the end of treatment to measure each patient 's degree of satisfaction . Tele-VR treated patients showed median values equal to or higher than the VR group patients in all 12 items investigated , except one . In motor performance , the Tele-VR group improved significantly ( P ≤ 0.05 ) , while the VR group showed no significant change . Patients assigned to the Tele-VR group were able to engage in therapy at home and the videoconferencing system ensured a good relationship between the patient and the physical therapist whose physical proximity was not required Background and Purpose — Telemedicine techniques can be used to address the rural – metropolitan disparity in acute stroke care . The Stroke Team Remote Evaluation Using a Digital Observation Camera ( STRokE DOC ) trial reported more accurate decision making for telemedicine consultations compared with telephone-only and that the California-based research network facilitated a high rate of thrombolysis use , improved data collection , low risk of complications , low technical complications , and favorable assessment times . The main objective of the STRokE DOC Arizona TIME ( The Initial Mayo Clinic Experience ) trial was to determine the feasibility of establishing , de novo , a single-hub , multirural spoke hospital telestroke research network across a large geographical area in Arizona by replicating the STRokE DOC protocol . Methods — Methods included prospect i ve , single-hub , 2-spoke , r and omized , blinded , controlled trial of a 2-way , site-independent , audiovisual telemedicine system design ed for remote examination of adult patients with acute stroke versus telephone consultation to assess eligibility for treatment with intravenous thrombolysis . The primary outcome measure was whether the decision to give thrombolysis was correct . Secondary outcomes were rate of thrombolytic use , 90-day functional outcomes , incidence of intracerebral hemorrhages , and technical observations . Results — From December 2007 to October 2008 , 54 patients were assessed , 27 of whom were r and omized to each arm . Mean National Institutes of Health Stroke Scale score at presentation was 7.3 ( SD 6.2 ) points . No consultations were aborted ; however , technical problems ( 74 % ) were prevalent in the telemedicine arm . Overall , the correct treatment decision was established in 87 % of the consultations . Both modalities , telephone ( 89 % correct ) and telemedicine ( 85 % correct ) , performed well . Intravenous thrombolytic treatment was used in 30 % of the telemedicine and telephone consultations . Good functional outcomes at 90 days were not significantly different . There were no statistically significant differences in mortality ( 4 % in telemedicine and 11 % in telephone ) or rates of intracerebral hemorrhage ( 4 % in telemedicine and 0 % in telephone ) . Conclusions — It is feasible to extend the original STRokE DOC trial protocol to a new state and establish an operational single-hub , multispoke rural hospital telestroke research network in Arizona . The trial was not design ed to have sufficient power to detect a difference between the 2 consultative modes : telemedicine and telephone-only . Whether by telemedicine or telephone consultative modalities , there were appropriate treatment decisions , high rates of thrombolysis use , improved data collection , low rates of intracerebral hemorrhage , and equally favorable time requirements . The learning curve was steep for the hub and spoke personnel of the new telestroke network , as reflected by frequent technical problems . Overall , the results support the effectiveness of highly organized and structured stroke telemedicine networks for extending expert stroke care into rural remote communities lacking sufficient neurological expertise Background and Purpose — Despite Food and Drug Administration approval of tissue-type plasminogen activator for stroke , obstacles in the US healthcare system prevent its widespread use . The Remote Evaluation for Acute Ischemic Stroke ( REACH ) program was developed to address these issues in rural setting s. A key component of stroke assessment in the REACH system is the National Institutes of Health Stroke Scale ( NIHSS ) evaluation . We sought to determine whether , using the REACH system , NIHSS values of bedside and remote evaluators would correspond . Methods — Twenty patients were recruited . On obtaining consent , a neurologist performed a bedside NIHSS evaluation on each patient . Within 1 hour , using any broadb and -connected workstation — either office or home personal computer and a l and line phone to speak with the patient — a second neurologist remotely evaluated the patient through the REACH system . Paired t tests and Pearson correlation coefficients were used to examine NIHSS reliability performed bedside and remotely . Results — NIHSS ranged from 1 to 24 . Correlations between bedside and remote locations ( r = 0.9552 , P = 0.0001 ) were very strong , and t tests indicate that the means were not different . Conclusions — The NIHSS can be reliably performed over the REACH system . This supports our endeavor to bring stroke expertise to rural community hospitals We conducted a r and omized controlled multicentre trial to investigate the feasibility of a telerehabilitation intervention for arm/h and function ( the Home Care Activity Desk [ HCAD ] training ) in a home setting . Usual care was compared to HCAD training . The hypothesis was that the clinical outcomes of the HCAD intervention would be at least the same as those measured after a period of usual care for patients with stroke , traumatic brain injury ( TBI ) and multiple sclerosis ( MS ) with respect to their arm/h and function . Eighty-one patients with affected arm/h and function result ing from either stroke , MS or TBI were recruited in Italy , Spain and Belgium ; 11 were lost during follow-up ( 14 % ) . The outcome measures were the Action Research Arm Test ( ARAT ) and the Nine Hole Peg Test ( NHPT ) . There were no significant differences between the two groups on the outcome measures ( ARAT and NHPT ) ; in both groups , patients maintained or even improved their arm/h and function . The HCAD training was found to be as feasible as usual care in terms of clinical outcomes , and both therapists and patients were satisfied with the HCAD intervention . A telerehabilitation intervention using HCAD may increase the efficiency of care BACKGROUND To increase the effective use of thrombolytics for acute stroke , the expertise of vascular neurologists must be disseminated more widely . We prospect ively assessed whether telemedicine ( real-time , two-way audio and video , and digital imaging and communications in medicine [ DICOM ] interpretation ) or telephone was superior for decision making in acute telemedicine consultations . METHODS From January , 2004 , to August , 2007 , patients older than 18 years who presented with acute stroke symptoms at one of four remote spoke sites were r and omly assigned , through a web-based , permuted blocks system , to telemedicine or telephone consultation to assess their suitability for treatment with thrombolytics , on the basis of st and ard criteria . The primary outcome measure was whether the decision to give thrombolytic treatment was correct , as determined by central adjudication . Secondary outcomes were the rate of thrombolytic use , 90-day functional outcomes ( Barthel index [ BI ] and modified Rankin scale [ mRS ] ) , the incidence of intracerebral haemorrhages , and technical observations . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00283868 . FINDINGS 234 patients were assessed prospect ively . 111 patients were r and omised to telemedicine , and 111 patients were r and omised to telephone consultation ; 207 completed the study . Mean National Institutes of Health stroke scale score at presentation was 9.5 ( SD 8.1 ) points ( 11.4 [ 8.7 ] points in the telemedicine group versus 7.7 [ 7.0 ] points in the telephone group ; p=0.002 ) . One telemedicine consultation was aborted for technical reasons , although it was included in the analyses . Correct treatment decisions were made more often in the telemedicine group than in the telephone group ( 108 [ 98 % ] vs 91 [ 82 % ] , odds ratio [ OR ] 10.9 , 95 % CI 2.7 - 44.6 ; p=0.0009 ) . Intravenous thrombolytics were used at an overall rate of 25 % ( 31 [ 28 % ] telemedicine vs 25 [ 23 % ] telephone , 1.3 , 0.7 - 2.5 ; p=0.43 ) . 90-day functional outcomes were not different for BI ( 95 - 100 ) ( 0.6 , 0.4 - 1.1 ; p=0.13 ) or for mRS score ( 0.6 , 0.3 - 1.1 ; p=0.09 ) . There was no difference in mortality ( 1.6 , 0.8 - 3.4 ; p=0.27 ) or rates of intracerebral haemorrhage after treatment with thrombolytics ( 2 [ 7 % ] telemedicine vs 2 [ 8 % ] telephone , 0.8 , 0.1 - 6.3 ; p=1.0 ) . However , there were more incomplete data in the telephone group than in the telemedicine group ( 12%vs 3 % , 0.2 , 0.1 - 0.3 ; p=0.0001 ) . INTERPRETATION The authors of this trial report that stroke telemedicine consultations result in more accurate decision making compared with telephone consultations and can serve as a model for the effectiveness of telemedicine in other medical specialties . The more appropriate decisions , high rates of thrombolysis use , improved data collection , low rate of intracerebr Output:	The use of telemedicine for post-stroke care is nascent and is primarily focused on post-stroke rehabilitation
MS22141	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Although idiopathic membranous nephropathy ( IMN ) is the most common cause of adult-onset nephrotic syndrome , the management of IMN remains controversial . The aim of this prospect i ve study was to compare the efficacy and drug safety of tacrolimus with that of cyclophosphamide ( CTX ; control group ) in IMN patients receiving corticosteroid therapy . A total of 100 IMN patients with nephrotic syndrome were r and omly assigned to receive a combination of corticosteroid therapy and either CTX or tacrolimus . During a follow-up period of at least 18 months , the remission rate after 2 months in the tacrolimus group was 65.1 % , which was higher than that of the CTX group ( 44.2 % ) ( p = 0.02 ) . The mean time to partial or complete remission was 2.20 months in the tacrolimus group and 3.92 months in the CTX group ( p < 0.001 ) . We also found significantly greater improvements in the serum albumin levels in the tacrolimus group compared with the CTX group at the 2-month ( p = 0.003 ) and 3-month time points ( p = 0.01 ) . The serum creatinine levels remained stable in both groups . Although remission was quicker and more common in the tacrolimus group ( compared with the CTX group ) before 3 months , there was no superiority of tacrolimus after 6 months . Glucose intolerance , urinary tract infections , and pneumonia were the major side effects observed in this study . All of the side effects were mild and controlled , and there were fewer side effects in the tacrolimus group compared with the CTX group , indicating a better treatment tolerance in the tacrolimus group BACKGROUND Evidence regarding the optimal dose of tacrolimus ( TAC ) in treatment of idiopathic membranous nephropathy ( IMN ) remains inconclusive . The objective of this study was to evaluate the efficacy and safety of low-dose TAC combined with prednisone for patients with IMN . METHODS We conducted a r and omized prospect i ve cohort study in IMN patients : 28 patients received oral TAC ( target whole blood concentration of 2 - 4 ng/mL ) plus prednisone for 12 months , and 28 patients received prednisone combined with intravenous cyclophosphamide ( CYC ) ( 750 mg/m2 body surface ) once every 4 weeks for 24 weeks . RESULTS Of the 56 patients who completed the 12-month treatment , complete remission ( CR ) occurred in 8 ( 28.6 % ) of the CYC group and 18 ( 64.3 % ) of the TAC group ; partial remission ( PR ) occurred in 10 ( 35.7 % ) of the CYC group and 7 ( 25.0 % ) of the TAC group . The probability of remission ( either CR or PR ) was higher in the TAC group than in the CYC group ( p = 0.0439 , by log-rank test ) . Furthermore , a significantly greater improvement in proteinuria and serum albumin levels was observed in the TAC group compared with the CYC group . Patients treated with TAC can often show a rapid increase in their serum albumin levels before any obvious reduction of urinary protein excretion . Side effects were mild and transitory in both groups . CONCLUSION The results demonstrated that the combined therapy of low-dose TAC and prednisone is an effective and safe therapeutic method for Chinese adults with IMN . Low-dose TAC accompanied by prednisone is enough to induce remission in the majority of patients with IMN BACKGROUND Calcineurin inhibitors are the most commonly used immunosuppressive drugs in liver transplantation , but the optimum initial immunosuppression regimen is not known . The aim of our study was to compare tacrolimus with microemulsified ciclosporin , in a regimen with st and ardised concomitant immunosuppressive therapy . METHODS In all liver transplant centres in the UK and Republic of Irel and , 606 patients undergoing a first orthotopic liver transplantation were r and omly assigned open-label tacrolimus or microemulsified ciclosporin . Primary outcome was the combined frequency ( whichever occurred first ) of death , retransplantation , or treatment failure for immunological reasons , analysed by intention to treat . FINDINGS 96 % of patients received the treatment allocated to them . The primary outcome was reached in 62 ( 21 % ) of 301 patients in the tacrolimus group versus 99 ( 32 % ) of 305 allocated microemulsified ciclosporin ( relative risk 0.63 [ 95 % CI 0.48 - 0.84 ] , p=0.001 ; time-to-event analysis log-rank test p=0.002 ) : deaths ( 50 [ 17 % ] vs 72 [ 24 % ] ) ; retransplantations ( 11 [ 4 % ] vs 31 [ 10 % ] ) treatment failure for immunological reasons ( 6 [ 2 % ] vs 12 [ 4 % ] ) . The relative risk for the composite outcome was in favour of tacrolimus . The main causes of death in both trial groups were sepsis and multiple organ failure ( 31 [ 10 % ] vs 30 [ 10 % ] ) , and the main cause for retransplantation was hepatic artery thrombosis ( 6 [ 2 % ] vs 17 [ 6 % ] ) . Renal dysfunction and the need for antihypertensive therapy were much the same in both groups . Tacrolimus was more diabetogenic . INTERPRETATION Clinical outcome at 1 year was better with tacrolimus-based immunosuppression than with microemulsified ciclosporin during the first year after liver transplantation . Tacrolimus should be the first choice of calcineurin inhibitor for patients receiving their first liver graft BACKGROUND AND OBJECTIVES Cyclophosphamide treatment improves renal survival in patients with idiopathic membranous nephropathy . However , use of cyclophosphamide is associated with cancer . The incidence of malignancies in patients with idiopathic membranous nephropathy was evaluated , and the cancer risk associated with cyclophosphamide use was estimated . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS Patients who attended the clinic were included prospect ively from 1995 on . A crude incidence ratio for the occurrence of malignancy was calculated . Incidence ratios were subsequently st and ardized to potential confounders . Latency between cyclophosphamide therapy and the occurrence of cancer was estimated by stratifying for time since the start of treatment . Finally , Poisson regression was used to obtain a multiple adjusted incidence ratio and investigate the dose-response relationship between cyclophosphamide and cancer . RESULTS Data were available for 272 patients ; the mean age was 51 years , and 70 % of the patients were men . Median follow-up was 6.0 years ( interquartile range=3.6 - 9.5 ) , and 127 patients were treated with cyclophosphamide . Cancer incidence was 21.2 per 1000 person-years in treated patients compared with 4.6 per 1000 person-years in patients who did not receive cyclophosphamide , result ing in crude and adjusted incidence ratios of 4.6 ( 95 % confidence interval , 1.5 to 18.8 ) and 3.2 ( 95 % confidence interval , 1.0 to 9.5 ) , respectively . CONCLUSION Cyclophosphamide therapy in idiopathic membranous nephropathy gives a threefold increase in cancer risk . For the average patient , this finding translates into an increase in annual risk from approximately 0.3 % to 1.0 % . The increased risk of malignancy must be balanced against the improved renal survival BACKGROUND To examine whether tacrolimus is more effective and safe than cyclosporine ( CsA ) in inducing remission in patients with steroid-resistant nephrotic syndrome ( SRNS ) . STUDY DESIGN R and omized controlled trial , nonblind , parallel group . SETTING S & PARTICIPANTS Tertiary-care hospital ; 41 consecutive patients with idiopathic SRNS , estimated glomerular filtration rate greater than 60 mL/min/1.73 m(2 ) , and histological characteristics showing minimal change disease , focal segmental glomerulosclerosis , or mesangioproliferative glomerulonephritis were r and omly assigned to treatment with tacrolimus ( n = 21 ) or CsA ( n = 20 ) . INTERVENTION Tacrolimus ( 0.1 to 0.2 mg/kg/d ) or CsA ( 5 to 6 mg/kg/d ) for 1 year ; cotreatment with alternate-day prednisolone and enalapril . OUTCOMES Patients achieving complete remission ( urinary protein-creatinine ratio < 0.2 g/g and serum albumin > or = 2.5 g/dL ) or partial remission ( urinary protein-creatinine ratio , 0.2 to 2 g/g , and serum albumin > or = 2.5 g/dL ) at 6 and 12 months ; time to remission ; proportion with relapses ; side effects . RESULTS No patient was lost to follow-up . After 6 months of therapy , remission occurred in 18 ( 85.7 % ) and 16 patients ( 80 % ) treated with tacrolimus and CsA , respectively ( relative risk [ RR ] , 1.07 ; 95 % confidence interval [ CI ] , 0.81 to 1.41 ) . Rates of remission at 12 months were also similar ( RR , 1.14 ; 95 % CI , 0.84 to 1.55 ) . The proportion of patients who experienced relapse was significantly greater in those receiving CsA compared with tacrolimus ( RR , 4.5 ; 95 % CI , 1.1 to 18.2 ; P = 0.01 ) . The decrease in blood cholesterol levels was greater with tacrolimus compared with CsA ( difference in mean values , 45.1 mg/dL ; 95 % CI , 19.1 to 71.2 ) . Persistent nephrotoxicity necessitating stoppage of medicine was seen in 4.7 % and 10 % patients , respectively . Cosmetic side effects ( hypertrichosis and gum hypertrophy ) were significantly more frequent in CsA-treated patients ( P < 0.001 ) . LIMITATIONS Single-center study , small sample size , and short duration of follow-up . CONCLUSIONS Tacrolimus or CsA in combination with low-dose steroids show similar efficacy in inducing remission in patients with SRNS . Therapy with tacrolimus is a promising alternative to CsA in view of the lower risk of relapses and lack of cosmetic side effects BACKGROUND Membranous nephropathy is a common cause of nephrotic syndrome ( NS ) in adults . Its treatment is still under debate . METHODS We report our experience in a pilot study using initially low doses of steroids and tacrolimus ( Tac ) . After 3 months of treatment , mycophenolate mofetil ( MMF ) was added if the proteinuria was higher than 1 g/day . RESULTS In accordance with this st and ard , 21 patients entered the study . A proteinuria level lower than 1 g/day was reached at month 3 of therapy with steroids and Tac in 11 patients . These patients continued this treatment for 12 months . MMF was added in nine cases after the third month and triple therapy was maintained for 12 more months . Two patients were withdrawn because of side effects . At the end of the treatment , remission of the NS was present in 15 out of all the patients ( 71.4 % ) . Remission of the NS was complete in eight ( 53.3 % ) patients and partial in seven ( 46.7 % ) others . The remaining four patients did not respond . There were no significant changes in renal function . At a mean time of 23.1 months after treatment was discontinued , 11 ( 73.3 % ) patients had relapsed . CONCLUSIONS In this trial , treatment with tacrolimus showed a good efficacy but a high relapse rate when it was discontinued Membranous nephropathy is a common cause of nephrotic syndrome in adults . Although some patients with membranous nephropathy achieve a spontaneous remission , renal function continues to deteriorate in others . We conducted a prospect i ve r and omized trial evaluating monotherapy with tacrolimus to achieve complete or partial remission in patients with biopsy-proven membranous nephropathy . Twenty-five patients received tacrolimus ( 0.05 mg/kg/day ) over 12 months with a 6-month taper , whereas 23 patients were in the control group . The probability of remission in the treatment group was 58 , 82 , and 94 % after 6 , 12 , and 18 months but only 10 , 24 , and 35 % , respectively in the control group . The decrease in proteinuria was significantly greater in the treatment group . Notably , six patients in the control group and only one in the treatment group reached the secondary end point of a 50 % increase in their serum creatinine . No patient in the tacrolimus group showed a relapse during the taper period . Nephrotic syndrome reappeared in almost half of the patients who were in remission by the 18th month after tacrolimus withdrawal . We conclude that tacrolim Output:	The cyclophosphamide group had a significantly higher risk of leukopenia , whereas the tacrolimus group had significantly higher rates of tremor .
MS22142	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background —This study evaluated the hypothesis that transendocardial injections of autologous mononuclear bone marrow cells in patients with end-stage ischemic heart disease could safely promote neovascularization and improve perfusion and myocardial contractility . Methods and Results —Twenty-one patients were enrolled in this prospect i ve , nonr and omized , open-label study ( first 14 patients , treatment ; last 7 patients , control ) . Baseline evaluations included complete clinical and laboratory evaluations , exercise stress ( ramp treadmill ) , 2D Doppler echocardiogram , single-photon emission computed tomography perfusion scan , and 24-hour Holter monitoring . Bone marrow mononuclear cells were harvested , isolated , washed , and resuspended in saline for injection by NOGA catheter ( 15 injections of 0.2 cc ) . Electromechanical mapping was used to identify viable myocardium ( unipolar voltage ≥6.9 mV ) for treatment . Treated and control patients underwent 2-month noninvasive follow-up , and treated patients alone underwent a 4-month invasive follow-up according to st and ard protocol s and with the same procedures used as at baseline . Patient population demographics and exercise test variables did not differ significantly between the treatment and control groups ; only serum creatinine and brain natriuretic peptide levels varied in laboratory evaluations at follow-up , being relatively higher in control patients . At 2 months , there was a significant reduction in total reversible defect and improvement in global left ventricular function within the treatment group and between the treatment and control groups ( P = 0.02 ) on quantitative single-photon emission computed tomography analysis . At 4 months , there was improvement in ejection fraction from a baseline of 20 % to 29 % ( P = 0.003 ) and a reduction in end-systolic volume ( P = 0.03 ) in the treated patients . Electromechanical mapping revealed significant mechanical improvement of the injected segments ( P < 0.0005 ) at 4 months after treatment . Conclusions —Thus , the present study demonstrates the relative safety of intramyocardial injections of bone marrow – derived stem cells in humans with severe heart failure and the potential for improving myocardial blood flow with associated enhancement of regional and global left ventricular function Rationale : Ixmyelocel-T is associated with a wide range of biological activities relevant to tissue repair and regeneration . Objective : To evaluate the safety and efficacy of ixmyelocel-T in 2 prospect i ve r and omized phase 2A Trials administered via minithoracotomy or intramyocardial catheter injections in patients with dilated cardiomyopathy ( DCM ) stratified by ischemic or nonischemic status . Methods and Results : In IMPACT-DCM , patients were r and omized to either ixmyelocel-T or st and ard-of-care control in a 3:1 ratio ( n=39 ) ; ixmyelocel-T was administered intramyocardially via minithoracotomy . In Catheter-DCM , patients were r and omized to either ixmyelocel-T or st and ard of care control in a 2:1 ratio ( n=22 ) ; ixmyelocel-T was administered intramyocardially using the NOGA Myostar catheter . Only patients r and omized to ixmyelocel-T underwent bone marrow aspiration and injections . In the 2 studies , a total of 61 patients were r and omized , and 59 were treated or received st and ard of care . Fewer ischemic patients treated with ixmyelocel-T experienced a major adverse cardiovascular event during follow-up when compared with control patients . A similar benefit was not seen in the nonischemic patients . Heart failure exacerbation was the most common major adverse cardiovascular event . Ixmyelocel-T treatment was associated with improved New York Heart Association class , 6-minute walk distance , and Minnesota Living with Heart Failure Question naire scores in the ischemic population relative to control ; a similar trend was not observed in the nonischemic population . Conclusions : Intramyocardial injection with ixmyelocel-T reduces major adverse cardiovascular event and improves symptoms in patients with ischemic DCM but not in patients with nonischemic DCM AIMS Despite accumulated evidence that intracoronary bone marrow cell ( BMC ) therapy may be beneficial in acute myocardial infa rct ion , there are only limited data available on the effectiveness of BMC 's in chronic heart failure . The aim of this study was to quantitatively investigate ventricular haemodynamics , geometry , and contractility as well as the long-term clinical outcome of BMC treated patients with reduced left ventricular ejection fraction ( LVEF ) due to chronic ischaemic cardiomyopathy . METHODS AND RESULTS Patients with chronic heart failure ( n = 391 LVEF < or=35 % ) due to ischaemic cardiomyopathy were enrolled in the present study . Of these , 191 patients ( mean NYHA class 3.22 ) underwent intracoronary BMC therapy . The control group ( mean NYHA class 3.06 ) consisted of 200 patients with comparable LVEF . Assessment s of haemodynamics at rest and exercise , quantitative ventriculography , spiroergometry , 24 h Holter ECG , late potentials , and heart rate variability were analysed . Over 3 months to 5 years after intracoronary BMC therapy there was a significant improvement in haemodynamics ( e.g. LVEF , cardiac index ) , exercise capacity , oxygen uptake , and LV contractility . Importantly , there was a significant decrease in long-term mortality in the BMC treated patients compared with the control group . CONCLUSION Intracoronary BMC therapy improves ventricular performance , quality of life and survival in patients with heart failure . These effects were present when BMC were administered in addition to st and ard therapeutic regimes . No side effects were observed OBJECTIVES This study sought to evaluate the feasibility and safety of autologous bone marrow-derived and cardiogenically oriented mesenchymal stem cell therapy and to probe for signs of efficacy in patients with chronic heart failure . BACKGROUND In pre- clinical heart failure models , cardiopoietic stem cell therapy improves left ventricular function and blunts pathological remodeling . METHODS The C-CURE ( Cardiopoietic stem Cell therapy in heart failURE ) trial , a prospect i ve , multicenter , r and omized trial , was conducted in patients with heart failure of ischemic origin who received st and ard of care or st and ard of care plus lineage-specified stem cells . In the cell therapy arm , bone marrow was harvested and isolated mesenchymal stem cells were exposed to a cardiogenic cocktail . Derived cardiopoietic stem cells , meeting release criteria under Good Manufacturing Practice , were delivered by endomyocardial injections guided by left ventricular electromechanical mapping . Data acquisition and analysis were performed in blinded fashion . The primary endpoint was feasibility/safety at 2-year follow-up . Secondary endpoints included cardiac structure/function and measures of global clinical performance 6 months post-therapy . RESULTS Mesenchymal stem cell cocktail-based priming was achieved for each patient with the dose attained in 75 % and delivery without complications in 100 % of cases . There was no evidence of increased cardiac or systemic toxicity induced by cardiopoietic cell therapy . Left ventricular ejection fraction was improved by cell therapy ( from 27.5 ± 1.0 % to 34.5 ± 1.1 % ) versus st and ard of care alone ( from 27.8 ± 2.0 % to 28.0 ± 1.8 % , p < 0.0001 ) and was associated with a reduction in left ventricular end-systolic volume ( -24.8 ± 3.0 ml vs. -8.8 ± 3.9 ml , p < 0.001 ) . Cell therapy also improved the 6-min walk distance ( + 62 ± 18 m vs. -15 ± 20 m , p < 0.01 ) and provided a superior composite clinical score encompassing cardiac parameters in t and em with New York Heart Association functional class , quality of life , physical performance , hospitalization , and event-free survival . CONCLUSIONS The C-CURE trial implements the paradigm of lineage guidance in cell therapy . Cardiopoietic stem cell therapy was found feasible and safe with signs of benefit in chronic heart failure , meriting definitive clinical evaluation . ( C-Cure Clinical Trial ; NCT00810238 ) BACKGROUND Autologous adult stem cell transplantation has been touted as the latest tool in regenerative medical therapy . Its potential for use in cardiovascular disease has only recently been recognized . A r and omized study was conducted with a novel epicardial technique to deploy stem cells as an adjuvant to conventional revascularization therapy in patients with congestive heart failure . METHODS After institutional review board and government approval , adult autologous stem cell transplantation ( CD34 + ) was performed in patients with ischemic cardiomyopathy and an ejection fraction of less than 35 % who were scheduled for primary off-pump coronary artery bypass grafting . Preoperatively , the patients underwent echocardiography , stress thallium imaging single photon emission computed tomography , and cardiac catheterization to identify ischemic regions of the heart and to guide in the selection of stem cell injection sites . The patients were prospect ively r and omized before the operative therapy was performed . Patient follow-up was 1 , 3 , and 6 months with echocardiography , single photon emission computed tomography , and angiography . RESULTS There were 20 patients enrolled in the study . Ten patients had successful subepicardial transplantation of autologous stem cells into ischemic myocardium . The other 10 patients , the control group , only had off-pump coronary artery bypass grafting . There were 8 male and 2 female subjects in each group . The median number of grafts performed was 1 in both groups . On angiographic follow-up , all grafts were patent at 6 months . The ejection fractions of the off-pump coronary artery bypass grafting group versus the off-pump coronary artery bypass grafting plus stem cell transplantation group were as follows : preoperative , 30.7 % + /- 2.5 % versus 29.4 % + /- 3.6 % ; 1 month , 36.4 % + /- 2.6 % versus 42.1 % + /- 3.5 % ; 3 months , 36.5 % + /- 3.0 % versus 45.5 % + /- 2.2 % ; and 6 months , 37.2 % + /- 3.4 % versus 46.1 % + /- 1.9 % ( P < .001 ) . There were no perioperative arrhythmias or neurologic or ischemic myocardial events in either group . CONCLUSIONS Autologous stem cell transplantation led to significant improvement in cardiac function in patients undergoing off-pump coronary artery bypass grafting for ischemic cardiomyopathy . Further investigation is required to quantify the optimal timing and specific cellular effects of the therapy AIMS The SEISMIC study was an open-label , prospect i ve , r and omised study to assess the safety and feasibility of percutaneous myoblast implantation in heart failure patients with implanted cardioverter-defibrillators ( ICD ) . METHODS AND RESULTS Patients were r and omised 2:1 to autologous skeletal myoblast therapy vs. optimal medical treatment . The primary safety end-point was defined as the incidence of procedural and device related serious adverse events , whereas the efficacy endpoints were defined as the change in global LVEF by MUGA scan , change in NYHA classification of heart failure and in the distance achieved during a six-minute walk test ( 6MW ) at 6-month follow-up . Forty subjects were r and omised to the treatment arm ( n=26 ) , or to the control arm ( n=14 ) . There were 12 sustained arrhythmic events and one death after episodes of ventricular tachycardia ( VT ) in the treatment group and 14 events in the control group ( P = ns ) . At 6-month follow-up , 6MW distance improved by 60.3±54.1?meters in the treated group as compared to no improvement in the control group ( 0.4±185.7?meters ; P = ns ) . In the control group , 28.6 % experienced worsening of heart failure status ( 4/14 ) , while 14.3 % experienced an improvement in NYHA classification ( 2/14 ) . In the myoblast-treatment arm , one patient experienced a deterioration in NYHA classification ( 8.0 % ) , whereas five patients improved one or two classes ( 20.0 % ; P=0.06 ) . However , therapy did not improve global LVEF measured by MUGA at 6-month follow-up . CONCLUSIONS These data indicate that implantation of myoblasts in patients with HF is feasible , appears to be safe and may provide symptomatic relief , though no significant effect was detected on global LVEF Background — In an open-label blinded study , we compared intracoronary and transendocardial CD34 + cell transplantation in patients with nonischemic dilated cardiomyopathy . Methods and Results — Of the 40 patients with dilated cardiomyopathy , 20 were r and omized to receive intracoronary injection and Output:	Left ventricular ejection fraction ( LVEF ) was improved in the majority of trials after therapy . Cell delivery combined with coronary artery bypass grafting was associated with the greatest improvement in LVEF . Left ventricular end-systolic volume ( or diameter ) , New York Heart Association functional classification , quality of life , and exercise capacity were also improved in most studies after cell therapy . Most ICM trials demonstrated a significant improvement in perfusion defects , infa rct size , and myocardial viability . Stem cells are a promising therapeutic modality for patients with heart failure due to ICM or NICM .
MS22143	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Summary . Anticardiolipin antibodies , one of the family of ‘ antiphospholipid ’ antibodies , increase the risk of venous thromboembolism in the presence of autoimmune disease . Our objective was to determine prospect ively whether there is a positive association between anticardiolipin antibodies and venous thromboembolism in ostensibly healthy adults . We conducted a nested case – control study ( n = 317 patients and n = 655 control subjects ) in a longitudinal study of over 20 000 participants . Baseline ( prediagnosis ) anticardiolipin IgG and IgM antibodies were assessed by enzyme‐linked immunoassays . Venous thromboembolism was vali date d using st and ardized criteria for venous thrombosis and pulmonary embolism . There was no association between anticardiolipin antibodies and subsequent venous thromboembolism occurrence , overall or in any subgroup . For example , the multivariate‐adjusted relative risk was 0·88 ( 95 % confidence interval , 0·43 , 1·78 ) for greater than versus less than the 95th percentile of anticardiolipin IgG. In conclusion , in this general population sample , an elevated anticardiolipin antibody level was not a risk factor for venous thromboembolism Introduction – We have undertaken a prospect i ve study to measure anticardiolipin antibodies of IgG isotype within the first few hours of an acute non‐hemorrhagic stroke . Material and methods – We have collected blood sample s at entry from one hundred patients ( 53 men and 47 women ) , mean age 67.4 years , referred within 6 h of a first‐ever non‐hemorrhagic stroke , and from an equal number of age‐ and gender‐matched control patients . Results – IgG anticardiolipin antibodies were 10 GPL in 26 patients and in 5 controls ( p < 0.0001 , X2 test ) . After logistic regression analysis , increase of IgG anticardiolipin antibodies remained independently associated with stroke ( p = 0.0034 ) , together with hypertension ( p = 0.0009 ) and atrial fibrillation ( p = 0.0238 ) . Conclusion – Our data suggest that the occurrence of elevation of IgG anticardiolipin antibodies in stroke patients should ante date stroke onset and might be a risk factor per se OBJECTIVE To determine whether the presence of anticardiolipin antibodies is a risk factor for ischemic stroke and venous thrombosis in healthy adult men . DESIGN A nested , case-control study in a prospect i ve cohort . SETTING A nationwide study of physicians . PARTICIPANTS The study sample was drawn from the Physicians ' Health Study , a r and omized , double-blind , placebo-controlled trial of aspirin and beta-carotene in 22,071 male physicians . At entry , 68 % of the participants su bmi tted plasma sample s that were subsequently frozen at -80 degrees C. During 60.2 months of follow-up , follow-up for nonfatal outcomes was 99.7 % complete and ascertainment of fatal outcomes was 100 % complete . We identified men with documented ischemic stroke , deep venous thrombosis of the leg , or pulmonary embolus and for whom a plasma sample was available . A control was matched by age , smoking history , and length of follow-up to each of the 100 patients with ischemic stroke and the 90 patients with deep venous thrombosis or pulmonary embolus . MEASUREMENTS Plasma sample s were assessed for IgG anticardiolipin antibodies by enzyme-linked immunosorbent assay . The mean anticardiolipin antibody titers of the case patients in the two diagnostic groups ( ischemic stroke ; venous thrombosis or pulmonary embolus ) were compared with those of the control groups , and relative risks were calculated for patients in increasing percentile categories of anticardiolipin antibodies by conditional logistic regression . RESULTS The anticardiolipin antibody titers were higher in case patients with deep venous thrombosis and pulmonary embolus than in their matched controls ( P = 0.01 ) . Persons with anticardiolipin antibody titers above the 95th percentile had a relative risk for developing deep venous thrombosis or pulmonary embolus of 5.3 ( 95 % CI , 1.55 to 18.3 ; P = 0.01 ) . The anticardiolipin antibody titers in case patients with ischemic stroke and controls were not significantly different ( P > 0.2 ) , and no clear trend of higher risks among those with elevated levels of anticardiolipin antibodies was observed . CONCLUSION An anticardiolipin antibody level above the 95th percentile is an important risk factor for deep venous thrombosis or pulmonary embolus but not for ischemic stroke in healthy adult men CONTEXT The presence of antiphospholipid antibodies ( aPL ) has been associated with vascular occlusive events . However , the role of aPL in predicting ischemic events , particularly recurrent ischemic stroke , is controversial . OBJECTIVE To evaluate the effect of baseline aPL positivity ( ie , positivity for anticardiolipin antibodies [ aCL ] , lupus anticoagulant antibodies [ LA ] , or both ) on subsequent thrombo-occlusive events , including recurrent stroke . DESIGN , SETTING , AND PARTICIPANTS The Antiphospholipid Antibodies and Stroke Study ( APASS ) , a prospect i ve cohort study within the Warfarin vs Aspirin Recurrent Stroke Study ( WARSS ) , a r and omized double-blind trial ( N = 2206 ) conducted at multiple US clinical sites from June 1993 through June 2000 and comparing adjusted-dose warfarin ( target international normalized ratio , 1.4 - 2.8 ) and aspirin ( 325 mg/d ) for prevention of recurrent stroke or death . APASS participants were 1770 ( 80 % ) WARSS participants who consented to enroll in the APASS , with usable baseline blood sample s drawn prior to r and omization to the WARSS and analyzed for aPL status within 90 days of index stroke by a central independent laboratory . Quality assurance was performed on approximately 10 % of sample s by a second independent laboratory . MAIN OUTCOME MEASURE Two-year rate of the composite end point of death from any cause , ischemic stroke , transient ischemic attack , myocardial infa rct ion , deep vein thrombosis , pulmonary embolism , and other systemic thrombo-occlusive events . The primary analysis assessed the outcome associated with aPL positivity within each WARSS treatment group separately , after risk-factor adjustment ( since these aPL-positive vs aPL-negative comparisons were not r and omized ) . RESULTS Of the 1770 APASS patients , 720 ( 41 % ) were classified as aPL-positive and 1050 ( 59 % ) as aPL-negative . There was no increased risk of thrombo-occlusive events associated with baseline aPL status in patients treated with either warfarin ( relative risk [ RR ] , 0.99 ; 95 % confidence interval [ CI ] , 0.75 - 1.31 ; P = .94 ) , or aspirin ( RR , 0.94 ; 95 % CI , 0.70 - 1.28 ; P = .71 ) . The overall event rate was 22.2 % among aPL-positive and 21.8 % among aPL-negative patients . There was no treatment x aPL interaction ( P = .91 ) . Patients with baseline positivity for both LA and aCL antibodies tended to have a higher event rate ( 31.7 % ) than did patients who tested negative for both antibodies ( 24.0 % ) ( unadjusted RR , 1.36 ; 95 % CI , 0.97 - 1.92 ; P = .07 ) . Classification and regression tree analyses did not identify a specific LA test or aCL isotype or titer that was associated with increased risk of thrombo-occlusive event . CONCLUSIONS The presence of aPL ( either LA or aCL ) among patients with ischemic stroke does not predict either increased risk for subsequent vascular occlusive events over 2 years or a differential response to aspirin or warfarin therapy . Routine screening for aPL in patients with ischemic stroke does not appear warranted OBJECTIVE We carried out a prospect i ve analysis of clinical and analytical findings in individuals with antiphospholipid antibodies ( aPL ) . METHODS We prospect ively studied 404 individuals , classified in 2 groups : ( 1 ) patients with primary or secondary antiphospholipid syndrome ( APS , n = 226 ) ; and ( 2 ) asymptomatic carriers of aPL ( n = 178 ) . Patients with APS and thrombosis were treated with dicumarin , and an international normalized ratio around 3.0 ( range 2.5 - 3.5 ) was targeted . Asymptomatic carriers were not treated , but specific prophylaxis with low molecular weight heparin or aspirin was prescribed for the periods when individuals were at increased risk of thrombosis . Both groups of individuals were followed up at semester intervals for 36 months . RESULTS Patients with APS presented with venous ( n = 106 , 46.9 % ) and /or arterial ( n = 70 . 31 % ) thrombosis or fetal loss ( n = 58 out of 112 women of fertility age , 51.8 % ) . At the time of the first thrombotic event , 50.0 % of patients with APS had coincident risk factors for thrombosis ( previous surgery and prolonged immobilization were significantly associated with venous thrombosis , and hypercholesterolemia and arterial hypertension with arterial thrombosis ) . Eighteen patients with APS died during the study period . Recurrence of thrombosis in patients with APS was linked to insufficient anticoagulation . During the followup , no episode of thrombosis was detected in any asymptomatic carrier . The proportion of subjects with aPL was similar in patients and in asymptomatic carriers . The proportion of subjects with aPL decreased during the followup , in both patients and carriers . CONCLUSION Differences between patients and asymptomatic carriers with aPL are at least partially dependent on the proportion of coincident vascular risk factors . The decline in aPL during the followup defines a subgroup in which an anticoagulation suppression assay could be tried Our aim was to determine if anticardiolipin antibodies are an independent risk factor for ischemic stroke and to determine their influence on stroke type and clinical outcome . We prospect ively studied 194 consecutive patients with ischemic stroke admitted within 48 h of stroke . A control group consisted of 100 , age and sex matched , healthy individuals . Neurological and functional status was assessed on admission , at 30 days , and at 1 year . IgG anticardiolipin antibodies were significantly more frequent in stroke patients ( 25.3 % ) than controls ( 6 % , p < 0.05 ) . A multivariate analysis suggested that anticardiolipin antibodies are an independent risk factor for ischemic stroke in addition to hypertension and atrial fibrillation ( RR = 2.94 , p < 0.05 ) . Elevated IgG anticardiolipin antibodies were associated with cognitive impairment as measured by the Mini Mental State Examination at 30 days and at 1 year . IgG anticardiolipin antibodies did not correlate with stroke recurrence , or mortality at 30 days or 1 year To date very few studies that analyze the prevalence of anticardiolipin antibodies ( ACA ) in healthy subjects have been reported . No data based on a systematic analysis of normal subjects with positive ACA is available . The aim of the present study was to evaluate the prevalence of ACA ; its clinical significance and relationship to the lupus anticoagulant ( LA ) and other autoimmune parameters in an apparently healthy population . 552 normal blood donors from a blood bank were r and omly selected . ACA positive donors who consented were monitored over a period of twelve months and tested every three months . ACA ( IgG and IgM isotypes ) were quantitated by enzyme linked immunoassay ( ELISA ) . The prevalence for IgG ACA in our donor population was estimated to be 6.5 % , and 9.4 % for IgM ACA , which is similar to the one previously reported for IgG and slightly higher for IgM. It is worth noting that in our study ACA positive donors exhibited a progressive negativization . Eight donors with IgG ACA and seven with IgM ACA remained positive for nine months . Five donors with IgG ACA and four with IgM ACA had family history of thromboembolic disease . One donor with IgG ACA and two with IgM ACA had had unexplained miscarriages in the past . We did not find any relationship between ACA and LA , nor between ACA positivity and the clinical and laboratory data studied . Pseudopositivity for lues was not found . No thrombotic event occurred in donors that were positive for ACA during the 12-month follow-up PURPOSE To assess the natural history and risk factors for thrombosis in a large cohort of unselected patients with antiphospholipid antibodies . PATIENTS AND METHODS Three hundred sixty consecutive patients ( 118 males , 242 females , median age 39 Output:	LA and aCL were significantly associated with an increased risk of thrombosis , especially arterial , in patients without SLE .
MS22144	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVES To determine the prognostic role of orthostatic hypotension for cardiovascular disease ( CVD ) and all-cause mortality in elderly people . DESIGN Prospect i ve study . SETTING Community based . PARTICIPANTS Five thous and sixty-four subjects from the Rotterdam study aged 55 and older . MEASUREMENTS Orthostatic hypotension was measured using a Dinamap automatic blood pressure recorder . Orthostatic hypotension is defined as a decline in systolic blood pressure of 20 mmHg or more or a decline in diastolic blood pressure of 10 mmHg or more from supine to st and ing position at any of three measurements taken 1 , 2 , and 3 minutes after st and ing . RESULTS At baseline , 901 subjects had orthostatic hypotension . During follow-up , 668 subjects had coronary heart disease ( CHD ) ( mean follow-up 6.0 + /- 3.5 years ) , and 1,835 subjects died ( mean follow-up period 7.8 + /- 3.8 years ) . Orthostatic hypotension increased the risk of CHD ( hazard ratio (HR)=1.31 , 95 % confidence interval (CI)=1.08 - 1.57 ) and all-cause mortality ( HR=1.22 , 95 % CI=1.09 - 1.36 ) , in models adjusted for age and sex . The risk was slightly lower after additional adjustment for cardiovascular risk factors . In analyses stratified for age , the HRs for all-cause mortality were 1.80 ( 95 % CI 1.25 - 2.60 ) , 1.13 ( 0.89 - 1.42 ) , and 1.27 ( 95 % CI=1.11 - 1.44 ) , in the first , second , and third tertile of age , respectively . CONCLUSION Orthostatic hypotension increases the risk of CHD and all-cause mortality in elderly people . The risk of CVD and mortality is strongest in younger and very old subjects Background Falls are a major cause of morbidity and mortality in dementia , but there have been no prospect i ve studies of risk factors for falling specific to this patient population , and no successful falls intervention/prevention trials . This prospect i ve study aim ed to identify modifiable risk factors for falling in older people with mild to moderate dementia . Methods and Findings 179 participants aged over 65 years were recruited from outpatient clinics in the UK ( 38 Alzheimer 's disease ( AD ) , 32 Vascular dementia ( VAD ) , 30 Dementia with Lewy bodies ( DLB ) , 40 Parkinson 's disease with dementia ( PDD ) , 39 healthy controls ) . A multifactorial assessment of baseline risk factors was performed and fall diaries were completed prospect ively for 12 months . Dementia participants experienced nearly 8 times more incident falls ( 9118/1000 person-years ) than controls ( 1023/1000 person-years ; incidence density ratio : 7.58 , 3.11–18.5 ) . In dementia , significant univariate predictors of sustaining at least one fall included diagnosis of Lewy body disorder ( proportional hazard ratio ( HR ) adjusted for age and sex : 3.33 , 2.11–5.26 ) , and history of falls in the preceding 12 months ( HR : 2.52 , 1.52–4.17 ) . In multivariate analyses , significant potentially modifiable predictors were symptomatic orthostatic hypotension ( HR : 2.13 , 1.19–3.80 ) , autonomic symptom score ( HR per point 0–36 : 1.055 , 1.012–1.099 ) , and Cornell depression score ( HR per point 0–40 : 1.053 , 1.01–1.099 ) . Higher levels of physical activity were protective ( HR per point 0–9 : 0.827 , 0.716–0.956 ) . Conclusions The management of symptomatic orthostatic hypotension , autonomic symptoms and depression , and the encouragement of physical activity may provide the core elements for the most fruitful strategy to reduce falls in people with dementia . R and omised controlled trials to assess such a strategy are a priority BACKGROUND Previous studies have reported a higher prevalence of dementia in persons with low blood pressure . OBJECTIVE To examine whether low blood pressure is prospect ively associated with the occurrence of Alzheimer disease and dementia in elderly people . SUBJECTS AND METHODS A community-based , dementia-free cohort ( n = 1270 ) aged 75 to 101 years was longitudinally examined twice within 6 years to detect incident dementia using the Diagnostic and Statistical Manual of Mental Disorders , Revised Third Edition criteria . Cox proportional hazards models were used to analyze blood pressure in association with dementia after adjustment for several potential confounders . RESULTS During the 6-year period , 339 subjects were diagnosed with dementia , including 256 persons with Alzheimer disease . Subjects with very high systolic pressure ( > 180 vs 141 - 180 mm Hg ) had an adjusted relative risk of 1.5 ( 95 % confidence interval [ CI ] , 1.0 - 2.3 ; P = .07 ) for Alzheimer disease , and 1.6 ( 95 % CI , 1.1 - 2.2 ) for dementia . Low systolic pressure ( < /=140 mm Hg ) was not related to incident dementia . In contrast , high diastolic pressure ( > 90 mm Hg ) was not associated with dementia incidence , whereas extremely low diastolic pressure ( < /=65 vs 66 - 90 mm Hg ) produced an adjusted relative risk of 1.7 ( 95 % CI , 1.1 - 2.4 ) for Alzheimer disease and 1.5 ( 95 % CI , 1.0 - 2.1 ; P = .03 ) for dementia . The latter association was pronounced particularly in persons who used antihypertensive drugs . CONCLUSIONS Both low diastolic and high systolic pressure are associated with an increased risk of Alzheimer disease and dementia in this elderly population . The atherosclerotic process may explain the observed associations . In addition , low diastolic pressure may increase dementia risk by affecting cerebral perfusion Background and Purpose — A long-term follow-up study was conducted in patients with lacunar infa rct to assess how 24-hour blood pressure monitoring values and MRI findings , in particular lacunar infa rcts and diffuse white matter lesions , can predict subsequent development of dementia and vascular events , which include cerebrovascular and cardiovascular events . Methods — One hundred seventy-seven patients were tracked for a mean of 8.9 years of follow-up . Documented events comprise the development of dementia and the occurrence of vascular events . The predictors for developing dementia and vascular events were separately evaluated by Cox proportional hazards analysis . Results — Twenty-six patients developed dementia ( 0.17/100 patient-years ) . Male sex ( relative risk [ RR ] , 4.2 ; 95 % CI , 1.2 to 14.7 ) , cognitive impairment ( RR , 3.0 ; 95 % CI , 1.0 to 8.5 ) , confluent DWML ( moderate : RR , 7.1 ; 95 % CI , 1.6 to 31.5 ; severe : RR , 35.8 ; 95 % CI , 7.2 to 177.3 ) , and nondipping status ( RR , 7.1 ; 95 % CI , 2.2 to 22.0 ) were independent predictors for dementia . Forty-six patients suffered from vascular events ( 3.11/100 patient-years ) . Diabetes mellitus ( RR , 5.7 ; 95 % CI , 2.7 to 11.9 ) , multiple lacunae ( moderate : RR , 6.4 ; 95 % CI , 2.5 to 15.8 ; severe : RR , 8.5 ; 95 % CI , 3.1 to 23.3 ) , and high 24-hour systolic blood pressure ( > 145 mm Hg versus < 130 mm Hg ) ( RR , 10.3 ; 95 % CI , 1.3 to 81.3 ) were independent predictors for vascular events . Conclusions — Predictors for developing dementia and vascular events appear to differ . Male sex , confluent diffuse white matter lesions , and nondipping status were independent predictors for subsequent development of dementia , while diabetes mellitus , multiple lacunae , and high 24-hour systolic blood pressure were independent predictors for vascular events Objectives Home blood pressure measurement ( HBPM ) is recommended by guidelines for hypertension management . However , this method might be difficult to use in elderly individuals with cognitive disorders . Our aim was to assess the agreement and the feasibility of HBPM by a relative as compared with 24-h ambulatory blood pressure monitoring ( ABPM ) in elderly patients with dementia . Methods Sixty out patients with dementia aged 75 years and older with office hypertension ( ≥140/90 mmHg ) were subjected successively to HBPM by a trained relative and 24-h ABPM . The order of the two methods was r and omized . Current guidelines ’ thresholds for the diagnosis of hypertension were used . Results The mean ( SD ) age of the patients was 80.8 ( 6.1 ) years ( 55 % women ) and the mean ( SD ) mini-mental state examination score was 20.1 ( 6.9 ) . The feasibility of relative-HBPM was very high , with a 97 % success rate ( defined by ≥12/18 measurements reported ) . The blood pressure measurements were highly correlated between the two methods ( r=0.75 and 0.64 for systolic blood pressure and diastolic blood pressure , respectively ; P<0.001 for both ) . The agreement between the methods for the diagnosis of sustained hypertension and white-coat hypertension was excellent ( overall agreement , 92 % ; & kgr ; coefficient , 0.81 ; 95 % CI , 0.61–0.93 ) . Similar results were found for daytime-ABPM . Conclusion In cognitively impaired elderly patients , HBPM by a relative using an automated device was a good alternative to 24-h ABPM Background : The role of blood pressure ( BP ) as a risk factor for dementia is complex and may be age dependent . In very old individuals , low BP might increase risk for dementia , perhaps by reducing cerebral perfusion pressure . Methods : The association between BP and dementia was examined in the Bronx Aging Study , a prospect i ve study of 488 community-dwelling elderly individuals over age 75 , dementia-free at baseline ( 1980 to 1983 ) and followed at 12- to 18-month intervals . Subjects with baseline BP and with at least one follow-up visit were included ( n = 406 ) . Incident dementia was diagnosed using the criteria of the Diagnostic and Statistical Manual of Mental Disorders ( 3rd rev . ed . ) . Results : Over 21 years ( median 6.7 years ) , 122 subjects developed dementia ( 65 Alzheimer ’s disease [ AD ] , 28 vascular dementia , 29 other dementias ) . Relative risk of dementia increased for each 10-mm Hg decrement in diastolic ( hazard ratio [ HR ] 1.20 , 95 % CI 1.03 to 1.40 ) and mean arterial ( HR 1.16 , 95 % CI 1.02 to 1.32 ) pressure , adjusted for age , sex , and education . Low diastolic BP significantly influenced risk of developing AD but not vascular dementia . Upon examination of groups defined by BP , mildly to moderately raised systolic BP ( 140 to 179 mm Hg ) was associated with reduced risk for AD ( HR vs normal systolic BP group 0.55 , 95 % CI 0.32 to 0.96 ) , whereas low diastolic BP ( ≤70 mm Hg ) was associated with increased risk of AD ( HR vs normal diastolic BP group 1.91 , 95 % CI 1.05 to 3.48 ) . Subjects with persistent low BP over 2 years had higher risk of developing dementia ( HR 2.19 , 95 % CI 1.27 to 3.77 ) . Conclusions : Low diastolic pressure is associated with higher risk of dementia in elderly individuals over age 75 . Dementia risk was higher in subjects with persistently low BP Antihypertensive therapy based on the angiotensin-converting enzyme ( ACE ) inhibitor perindopril reduced the incidence of recurrent stroke in the Perindopril Protection against Recurrent Stroke Study ( PROGRESS ) . The present study assessed the effect of perindopril on the 24-h blood pressure ( BP ) in hypertensive patients with lacunar infa rct ion using ambulatory BP monitoring ( ABPM ) . There was a 4-week observation period , a 4-week treatment period 1 ( perindopril at 2 mg/day ) , and a 4-week treatment period Output:	The little available evidence suggested increased levels of dementia being associated with reduced tolerability . CONCLUSIONS ABPM is well tolerated in people with mild-moderate dementia and provides some additional information over and above office BP alone . However , few studies have addressed ABPM in people with more severe dementia
MS22145	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background : Schizophrenia has been associated with disturbances of thalamic functioning . In light of recent evidence suggesting a significant impact of the glutamatergic system on key symptoms of schizophrenia , we assessed whether modulation of the glutamatergic system via blockage of the N-methyl-d-aspartate (NMDA)-receptor might lead to changes of thalamic functional connectivity . Methods : Based on the ketamine model of psychosis , we investigated changes in cortico-thalamic functional connectivity by intravenous ketamine challenge during a 55-minute resting-state scan . Thirty healthy volunteers were measured with pharmacological functional magnetic resonance imaging using a double-blind , r and omized , placebo-controlled , crossover design . Results : Functional connectivity analysis revealed significant ketamine-specific changes within the thalamus hub network , more precisely , an increase of cortico-thalamic connectivity of the somatosensory and temporal cortex . Conclusions : Our results indicate that changes of thalamic functioning as described for schizophrenia can be partly mimicked by NMDA-receptor blockage . This adds substantial knowledge about the neurobiological mechanisms underlying the profound changes of perception and behavior during the application of NMDA-receptor antagonists Background Dysfunction of neuroplasticity due to N-methyl-d-aspartate ( NMDA ) receptor hypofunction may be a causal factor for memory and executive dysfunctioning in schizophrenia . Deregulation of NMDA transmission in the prefrontal cortex may also explain negative and positive symptoms . Clozapine augmentation with memantine targets altered NMDA receptor-mediated neurotransmission in schizophrenia and showed substantial beneficial effects on several symptom domains in a small proof-of-concept study . We evaluate effects of memantine add-on treatment to clozapine for memory and executive function , and negative and positive symptoms in schizophrenia . Method Clozapine-treated patients with refractory schizophrenia were r and omly assigned to 12 weeks of double-blind adjunctive treatment with memantine ( n = 26 ) or placebo ( n = 26 ) . Crossover occurred after a 2-week placebo wash-out period . Primary endpoints were change from baseline to 12 weeks treatment and 14 weeks to 26 weeks treatment on memory and executive function using the Cambridge Neuropsychological Test Automated Battery ( CANTAB ) , Positive and Negative Syndrome Scale ( PANSS ) , and Clinical Global Impression Severity Scale ( CGI-S ) . Side effects were assessed using the Liverpool University Neuroleptic Side-Effect Rating Scale . Results When compared with placebo , memantine improved a composite memory score comprising verbal recognition memory and paired associates learning task scores on the CANTAB ( effect size = 0.30 ) and PANSS negative subscale score ( effect size = 0.29 ) . Side effects were mild and transient . Conclusions In patients with clozapine-treated refractory schizophrenia , memantine addition significantly improved verbal and visual memory and negative symptoms without serious adverse effects . These results justify further investigations on long-term memantine augmentation to clozapine in treatment-resistant schizophrenia The " glutamate hypothesis of schizophrenia " has changed attitudes in the development of new medications . This study aim ed to evaluate the effects of 20 mg of memantine per day ( as a NMDA receptor antagonist ) added to risperidone among male patients with schizophrenia . In a r and omized placebo-controlled , double-blind clinical trial , 46 adult male patients with schizophrenia were evaluated in both intervention and control groups at weeks 0 , 6 and 12 . The positive and negative symptoms scale and the mini mental status examination were used to assess positive , negative and cognitive symptoms and general psychopathology . The mean age of the patients was 44.8 for the intervention group and 45.3 for the control group , and the mean times since diagnosis were 23.5 and 25.7 years in the intervention and the control group , respectively . Positive and general psychopathologic symptoms showed no significant differences between the two groups at baseline or after treatment ; while negative symptoms improved significantly in the intervention group at week 12 . Cognitive function was also significantly improved in the intervention group at weeks 6 and 12 . Memantine is supported as an effective adjunct treatment to improve negative and cognitive symptoms in patients with schizophrenia Rationale Pro-cognitive agents for chronic psychotic disorders ( CPDs ) might be detected via experimental medicine models , in which neural targets engaged by the drug predict sensitivity to the drug ’s pro-cognitive effects . Objective This study aims to use an experimental medicine model to test the hypothesis that “ target engagement ” predicts pro-cognitive effects of the NMDA antagonist , memantine ( MEM ) , in CPDs . Methods MATRICS Consensus Cognitive Battery ( MCCB ) performance was assessed in CPD ( n = 41 ) and healthy subjects ( HS ; n = 41 ) in a double-blind , r and omized cross-over design of acute ( single dose ) MEM ( placebo vs. 10 or 20 mg p.o . ) . Measures of prepulse inhibition ( PPI ) and mismatch negativity previously reported from this cohort substantiated target engagement . Biomarkers predicting MEM neurocognitive sensitivity were assessed . Results Testing confirmed MCCB deficits associated with CPD diagnosis , age , and anticholinergic exposure . MEM ( 20 mg p.o . ) reduced MCCB performance in HS . To control for significant test order effects , an “ order-corrected MEM effect ” ( OCME ) was calculated . In CPD subjects , greater age , positive MEM effects on PPI , and SNP rs1337697 ( within the ionotropic NMDA receptor gene , GRIN3A ) predicted greater positive OCME with 20 mg MEM . Conclusions An experimental medicine model to assess acute pro-cognitive drug effects in CPD subjects is feasible but not without challenges . A single MEM 20 mg dose had a negative impact on neurocognition among HS . In CPD patients , age , MEM effects on PPI , and rs1337697 predicted sensitivity to the neurocognitive effects of MEM . Any potential clinical utility of these predictive markers for pro-cognitive effects of MEM in subgroups of CPD patients can not be inferred without a validating clinical trial BACKGROUND Glutamate deregulation may be involved in the neuropathology of schizophrenia , mainly through N-methyl-d-aspartate ( NMDA ) receptor dysfunction . Memantine , a drug approved by the FDA for the treatment of moderate to severe Alzheimer 's disease , acts as a weak nonselective NMDA receptor antagonist . The aim of this study was to examine the efficacy of memantine as an adjunctive treatment to clozapine in patients with refractory schizophrenia . METHOD In this double-blind , placebo-controlled study , out patients with refractory schizophrenia according to DSM-IV clinical criteria were r and omly assigned , from March 2005 to February 2008 , to receive either 20 mg/d memantine ( n = 10 ) or placebo ( n = 11 ) , in addition to clozapine , for 12 weeks . The primary outcome measure was the total score on the 18-item Brief Psychiatry Rating Scale ( BPRS ) and BPRS subscales of positive and negative symptoms . Secondary outcomes were global severity of disease as measured by the Clinical Global Impressions scale ( CGI ) , cognition as assessed by the Mini-Mental State Examination ( MMSE ) , and extrapyramidal symptoms as assessed by the Simpson-Angus Scale ( SAS ) . RESULTS Twenty-one participants completed the study and were used in the analysis . Significant improvement ( P < .01 ) on the total BPRS score , its subscales of positive ( effect size [ ES ] = -1.38 ) and negative ( ES = -3.33 ) symptoms , the CGI score ( ES = 1.56 ) , and the MMSE score was observed with memantine as compared with placebo . No significant changes in extrapyramidal symptoms were observed . CONCLUSIONS Memantine add-on to clozapine therapy was associated with improvement in negative and positive symptoms in refractory schizophrenia patients . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00757978 Glutamate dysregulation may be involved in the neuropathology of schizophrenia . Memantine , a drug approved by the FDA for the treatment of moderate to severe Alzheimer 's disease , acts as a partial uncompetitive NMDA receptor antagonist . The aim of this study was to examine the efficacy of memantine as an adjunctive treatment to olanzapine in patients with schizophrenia . In this double-blind , placebo-controlled studies , patients with schizophrenia according to DSM-IV clinical criteria were selected . Patients were r and omly assigned to receive either memantine ( week 1:10 mg/day ; weeks 2 - 6:20 mg/day ) plus olanzapine ( 15 - 20 mg/day ) or olanzapine plus placebo . At baseline , no statistically significant difference regarding the mean total PANSS scores between treatment groups was found . Results showed that memantine significantly improved the positive and negative PANSS score in patients maintained on olanzapine after six weeks compared to olanzapine alone ( P<0.001 ) . Furthermore , female patients showed significantly better response than males , especially in positive PANSS score . No significant changes in extrapyramidal symptoms were observed . These findings indicate that olanzapine efficacy might be augmented with memantine . Furthermore , this effect is more remarkable in female patients with schizophrenia Background : Schizophrenia severely influences function and quality of life . The benefit of newer antipsychotics in improving the quality of life in schizophrenia still remains controversial . The aim of the present study is to evaluate the effect of memantine on global function and quality of life in patients with schizophrenia . Material s and Methods : This was a r and omized controlled trial on inpatient cases of schizophrenia in Noor University Hospital , Isfahan , Iran . A number of 64 patients were selected through sequential sampling ; patients were r and omly allocated in intervention and placebo groups . The intervention group was treated with memantine plus previously administered , stabled-dose , atypical antipsychotic , while the control group received placebo plus previously administered , stabled-dose , atypical antipsychotic . Memantine administration was initiated at 5 mg daily ; the dosage was increased at weekly intervals by 5 mg and finally up-titrated to 20 mg daily within 4 weeks . All patients were assessed by means of Global Assessment of Functioning ( GAF ) and quality of life scale ( QLS ) initially and every four weeks to the end of the 12th week . Results : Analysis of baseline GAF and QLS scores showed no significant differences between the two groups ( P = 0.081 and P = 0.225 , respectively ) . GAF and QLS scores increased in both groups ; but it was higher in the intervention group . The difference between the two groups was statistically significant . ( P < 0.001 and P < 0.001 , respectively ) memantine was well tolerated , with no significant side effects . Conclusion : Add-on memantine was significantly effective in improving the global function of patients as well as their quality of life Abstract We aim ed to evaluate the efficacy of memantine add-on in the treatment of primary negative symptoms of patients with stable schizophrenia . In a double-blind placebo-controlled clinical trial , 40 patients with schizophrenia ( Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition ) who were stabilized on risperidone for a minimum of 8 weeks were r and omized to either memantine ( 20 mg ) or placebo in addition to risperidone , 6 mg/d , for eight weeks . Assessment was done using the Positive and Negative Syndrome Scale at baseline , week 4 , and week 8 . The Hamilton Depression Rating Scale and the Extrapyramidal Symptom Rating Scale at baseline and week 8 were used to assess depression and extrapyramidal symptoms , respectively . All 40 patients had at least one postbaseline measurement , and 38 patients completed the trial . Patients in the memantine group showed a significantly greater improvement on negative subscale than the placebo group at end point ( P < 0.001 ) . The same effect was observed for the total score ( P < 0.001 ) and the general psychopathology subscale score ( P = 0.002 ) . There was no significant difference in reduction of positive symptoms score between the 2 groups ( P = 0.757 ) . Changes in the Hamilton Depression Rating Scale and the Extrapyramidal Symptom Rating Scale scores and frequency of adverse effects did not differ between the 2 groups . Our study showed that memantine is a tolerable and efficacious add-on treatment for primary negative symptoms of schizophrenia Output:	Conclusions Memantine add-on treatment may be beneficial for treating psychopathological symptoms ( especially negative symptoms ) in schizophrenia patients . The negative-symptom effect size may be associated with younger adult schizophrenia patients
MS22146	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Optimists ( people who have positive expectations about the future ) have been shown to perform more health-promoting behaviors than pessimists . This study attempts to alter individuals ’ levels of optimism , and thereby their health behaviors , by having them write about a positive future . HIV-infected women ( N = 40 ) on combination therapies were r and omly assigned to write about a positive future or assigned to a no-writing control group . Among participants who were low in optimism , the writing intervention led to increased optimism , a trend toward increased self-reported adherence to medications , and decreased distress from medication side effects , compared to controls who did not write . Participants who were high in optimism showed the opposite effects after writing about the future . Results suggest that a future-oriented writing intervention may be a promising technique to increase medication adherence and decrease symptom , distress in pessimistic individuals Background : We prospect ively studied the impact of an adherence counselor on the outcome of patients failing antiretroviral therapy because of nonadherence . Methods : Forty-six patients , identified as chronically nonadherent were enrolled . Individual attention was provided using the information , motivation and behavioral methodology . HIV RNA ( viral load , in copies/mL ) , CD4 count ( in cells/mm 3 ) , and body weight before and after the adherence counselor were measured . Qualitative outcome and patient satisfaction were assessed by deidentified third-party interviews . Results : Over half completed at least 1 year ; only 8 patients were lost to follow-up . Mean CD4 counts increased significantly ( P < .05 ) for completers at 6 and 12 months . Viral loads decreased between baseline and 6 months . Most clients reported subjective benefit from working with the adherence counselor . Conclusion : Although few clients showed complete virologic suppression , the value of an adherence counselor was vali date d. Longer term adherence programs should be evaluated A r and omized 2-group medication adherence intervention is evaluated with HIV-infected adults ( N = 141 ) assessed at baseline , 3- , and 9-month follow-ups . Cognitive ( self-efficacy , behavioral intent ) , mental health ( depression , well-being ) , and substance use indicators were the outcome measures . In addition , a posttest-only analysis from 3 to 9 months evaluates intervention impact on antiretroviral adherence , measured through Medication Event Monitoring System and pill counts . Compared to the st and ard care group , the intervention group showed significant increases in adherence self-efficacy and behavioral intent at 3 and 9 months and marginal improvements in mental health . Although the st and ard care group had higher adherence at 3 months ( no baseline data were available prior to intervention ) , intervention group patients showed significant increases in adherence from 3 to 9 months . Although adherence levels achieved by intervention patients may not be sufficient for virological control , this is one of the first studies to provide promising results of longer term effectiveness of a behavioral adherence intervention The impact of an adherence enhancement program for low income HIV-infected Spanish-speaking Latinos on health literacy , patient-provider relationships , and adherence to HAART was examined . Evaluations were conducted at baseline , 6 weeks , and 6 months for participants ( n = 85 ) r and omly assigned to either the intervention group or a comparison group ; 69 ( 81 % ) remained in the study for the entire 6-month duration . The intervention group scored significantly better than the comparison group on 3 of 5 measures of HIV health literacy at 6 weeks and on 2 of 5 measures , at 6 months . While there was a weak trend for the intervention group to report an increase in self-efficacy of medication adherence management , baseline to 6 weeks , no other changes were significant . Perceptions of the quality of relationship and communications with their HIV-treating physicians improved both at 6 weeks ( p = 0.04 ) and at 6 months ( p < 0.001 ) . The comparison group showed little change baseline to 6 weeks and baseline to 6 months . While there was a trend for the pilot group to report better medication adherence , these differences were not statistically significant . Further evaluation of the impact of this adherence enhancement program is needed Child sexual abuse ( CSA ) is associated with HIV risk behaviors [ Bensley , L. , Van Eenwyk , J. , and Simmons , K. W. , 2003 . ] and more prevalent among women living with HIV than in the general population [ Koenig , L. J. , and Clark , H. , 2004 ] . This r and omized Phase ~ I clinical trial tested the impact of a culturally congruent psychoeducational intervention design ed to reduce sexual risks and increase HIV medication adherence for HIV-positive women with CSA histories . An ethnically diverse sample of 147 women were r and omized to two conditions : an 11-session Enhanced Sexual Health Intervention ( ESHI ) or an attention control . Results based on “ intent to treat ’ ’ analysesof pre – post changes are reported here . Additional analyses explored whether theobserved effects might depend on “ intervention dose , ’ ’ i.e. , number of sessions attended . Women in the ESHI condition reported greater sexual risk reduction than women in the control condition . Although there were no differences between women in the ESHI and control groups on medication adherence , women in the ESHI condition who attended 8 or more sessions reported greater medication adherence at posttest than control women . The findings provide initial support for this culturally and gender-congruent psychoeducational intervention for HIV-positive women with CSA , and highlight the importance of addressing the effects of CSA on sexual risk reduction and medicationadherence in preventive interventions for women This study r and omized 90 HIV-seropositive , methadone-maintained injection drug users ( IDUs ) to an HIV Harm Reduction Program ( HHRP+ ) or to an active control that included harm reduction components recommended by the National AIDS Demonstration Research Project . The treatment phase lasted 6 months , with follow-ups at 6 and 9 months after treatment entry . Patients in both treatments showed reductions in risk behaviors . However , patients assigned to HHRP+ were less likely to use illicit opiates and were more likely to adhere to antiretroviral medications during treatment ; at follow-up , they had lower addiction severity scores and were less likely to have engaged in high risk behavior . Findings suggest that enhancing methadone maintenance with an intervention targeting HIV-seropositive IDUs increases both harm reduction and health promotion behaviors This study examined whether a self-management intervention based on feedback of adherence performance and principles of social cognitive theory improves adherence to antiretroviral dosing schedules . Forty-three individuals with HIV/AIDS who were starting or switching to a new protease inhibitor regimen were r and omly assigned to be in a medication self-management program or usual care control group . The self-management program included skills development exercises , three monthly visits for medication consultations , and monthly feedback of adherence performance using electronic monitors on medication bottles . Participants also completed a 40-item question naire that measured self-efficacy to take medications , on schedule , in a variety of situations . Logistic regression analysis indicated that individuals in the self-management group were significantly more likely to take 80 % or more of their doses each week than individuals in the control group ( n=29 , OR=7.8 , 95 % CI=2.2 - 28.1 ) . Self-management training with feedback of adherence performance is a potentially useful model for improving adherence to complex regimens in HIV/AIDS care Background . Patients cite " forgetting " as a reason for nonadherence to highly active antiretroviral therapy ( HAART ) . We measured the effect of a memory-prompting device on adherence to HAART in memory-intact and memory-impaired human immunodeficiency virus (HIV)-infected subjects . Methods . The study was a prospect i ve , r and omized , controlled trial involving 64 HIV-infected adults . The intervention was the Disease Management Assistance System ( DMAS ) device , combined with monthly adherence counseling . Control subjects received only adherence counseling . The DMAS was programmed with HAART regimen data to provide verbal reminders at dosing times . Adherence was measured for 24 weeks using electronic drug exposure monitor ( eDEM ) caps . Results . A total of 58 subjects completed the 24-week study period ; 28 were HAART naive ( 12 DMAS users and 16 control subjects ) . Mean adherence scores did not differ significantly between DMAS users ( 80 % ) and control subjects ( 65 % ) . Post hoc analysis of 31 memory-impaired subjects ( 14 DMAS users and 17 control subjects ) revealed significantly higher adherence rates among DMAS users ( 77 % ) , compared with control subjects ( 57 % ) ( P=.001 ) . However , analysis of memory-intact subjects showed that adherence was not significantly improved for DMAS users ( 83 % ) , compared with control subjects ( 77 % ) ( P=.25 ) . At week twelve , 38 % of the DMAS users and 14 % of the control subjects had an undetectable plasma HIV RNA load ( P=.014 ) , and at week 24 , the plasma HIV RNA load was undetectable for 34 % of the DMAS users and 38 % of the control subjects ( P=.49 ) . CD4(+ ) cell counts did not differ between the study arms . Virological and immunological responses were not related to DMAS use in memory-impaired subjects . Conclusion . The DMAS prompting device improved adherence for memory-impaired subjects but not for memory-intact subjects BACKGROUND Directly administered antiretroviral therapy ( DAART ) in methadone clinics has the potential to improve treatment outcomes for human immunodeficiency virus (HIV)-infected injection drug users ( IDUs ) . METHODS DAART was provided at 3 urban methadone clinics . Eighty-two participants who were initiating or reinitiating highly active antiretroviral therapy ( HAART ) received supervised doses of therapy at the clinic on the mornings on which they received methadone . Treatment outcomes in the DAART group were compared with outcomes in 3 groups of concurrent comparison patients , who were drawn from the Johns Hopkins HIV Cohort . The concurrent comparison patients were taking HAART on a self-administered basis . The 3 groups of concurrent comparison patients were as follows : patients with a history of IDU who were receiving methadone at the time HAART was used ( the IDU-methadone group ; 75 patients ) , patients with a history of IDU who were not receiving methadone at the time that HAART was used ( the IDU-nonmethadone group ; 244 patients ) , and patients with no history of IDU ( the non-IDU group ; 490 patients ) . RESULTS At 12 months , 56 % of DAART participants achieved an HIV type 1 RNA level < 400 copies/mL , compared with 32 % of participants in the IDU-methadone group ( P=.009 ) , 33 % of those in the IDU-nonmethadone group ( P=.001 ) , and 44 % of those in the non-IDU group ( P=.077 ) . The DAART group experienced a median increase in the CD4 cell count of 74 cells/mm3 , compared with 21 cells/mm3 in the IDU-methadone group ( P=.04 ) , 33 cells/mm3 in the IDU-nonmethadone group ( P=.09 ) , and 84 cells/mm3 in the non-IDU group ( P=.98 ) . After adjustment for other covariates in a logistic regression model , DAART participants were significantly more likely to achieve viral suppression than were patients in each of the 3 comparison groups . CONCLUSIONS These results suggest that methadone clinic-based DAART has the potential to provide substantial clinical benefit for HIV-infected IDUs A 24-week open-label clinical trial was conducted in 195 HIV-infected adults commonly underrepresented in research ( 35 % female , 71 % African American , 21 % Hispanic , and 20 % injection drug users [ IDUs ] ) to evaluate the effect of an HIV educational program on efficacy and adherence with a simple , compact , twice-daily triple nucleoside regimen containing a lamivudine ( 150 mg)/zidovudine ( 300 mg ) combination ( COM ) tablet plus abacavir ( ABC ) , 300 mg . At baseline , the patients ' median plasma HIV-1 RNA level was 4.18 log10 copies/mL and the median CD4 + cell count was 379 cells/mm3 . Patients were r and omized 1:1 to 4 modules of the Tools for Health and Empowerment HIV education intervention plus routine counseling ( EI + RC ; n = 96 ) or to routine counseling alone ( RC ; n = 99 ) . No differences between the EI + RC and RC treatment arms were observed with respect to the proportion of patients achieving plasma HIV-1 RNA levels < 40 copies/mL ( 60 % [ 33/55 ] vs. 55 % [ 38/69 ] ; P = 0.529 ) or < 400 copies/mL ( 80 % [ 44/55 ] vs. 80 % [ 55/69 ] ; P = 0.689 ) at week 24 ( intent-to-treat observed analysis ) , increase in median CD4 cell count above baseline at week 24 ( 78.3 vs. 104.8 cells/mm3 Output:	We discerned congruence between the prominence of substance abuse as a factor identified in the descriptive studies as a barrier to adherence and its prominence as the problem most addressed in those reports of intervention studies that specified the problems targeted for intervention . We also discerned congruence between the prominence of family and provider support as factors identified in the descriptive studies as facilitators of adherence and the presence of social support as an intervention component and outcome variable . Less discernible in the reports of intervention studies was specific attention to other factors prominent in the descriptive studies , which may be due to the complex nature of the problem , individualistic and rationalist slant of interventions , or simply the ways interventions were presented .
MS22147	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: This pilot aims to better underst and the market for childcare in Saudi Arabia – both the supply and dem and sides – and to design a r and omized controlled experiment to test whether access to affordable day care ( in the form of subsidies , for example ) would incentivize Saudi mothers to search actively for employment and to remain employed once they are hired . In addition , the study seeks to underst and the degree to which employment early on in one ’s life impacts employment in later stages . The pilot will provide information on the groups of women the experiment should target , appropriate levels for the childcare subsidy , and the quality and current geographic locations of daycare sites . Expected Impact Determine the effects of facilitating childcare access on Saudi women ’s employment . PRINCIPAL INVESTIGATORS  Boston University Patricia Cortes  Harvard University Claudia Goldin  Swarthmore College Jennifer Research Findings : This study examined processes of change associated with the positive preschool and kindergarten outcomes of children who received the Head Start REDI ( REsearch -based , Developmentally Informed ) intervention compared to usual practice Head Start . Using data from a large-scale r and omized controlled trial ( N = 356 children , 42 % African American or Latino , all from low-income families ) , this study tests the logic model that improving preschool social-emotional skills ( e.g. , emotion underst and ing , social problem solving , and positive social behavior ) as well as language /emergent literacy skills will promote cross-domain academic and behavioral adjustment after children transition into kindergarten . Validating this logic model , the present study finds that intervention effects on 3 important kindergarten outcomes ( e.g. , reading achievement , learning engagement , and positive social behavior ) were mediated by preschool gains in the proximal social-emotional and language /emergent literacy skills targeted by the REDI intervention . It is important to note that preschool gains in social-emotional skills made unique contributions to kindergarten outcomes in reading achievement and learning engagement , even after we accounted for concurrent preschool gains in vocabulary and emergent literacy skills . Practice or Policy : These findings highlight the importance of fostering at-risk children 's social-emotional skills during preschool as a means of promoting school readiness The Incredible Years ( IY ) Series includes separate group interventions to improve parenting interactions , teacher classroom management , and child social-emotional regulation . Although originally developed to treat early onset conduct problems , IY targets many of the proposed mechanisms and risk factors for internalizing distress in early childhood . Prior studies have demonstrated the effects of the IY parent intervention on co-occurring depressive symptoms . We attempted to extend these findings by examining the unique and combined effects of IY interventions on children 's co-occurring internalizing symptoms . One-hundred and fifty-nine families with children ages 4- to 8-years-old were r and omly assigned to parent training ( PT ) ; parent plus teacher training ( PT + TT ) ; child training ( CT ) ; child plus teacher training ( CT + TT ) ; parent , child , plus teacher training ( PT + CT + TT ) ; or a waiting list control group . Children who received any of the intervention components were more likely to have lower mother-rated internalizing symptoms at posttreatment compared to children in a wait-list control group . Implication s for future research and for design ing interventions and prevention strategies for children with internalizing symptoms are discussed . ( PsycINFO Data base This study evaluated the post-treatment outcome effects of a classroom-based social skills program for pre-kindergarten children , using a teacher-consultation model . The pre-K RECAP ( Reaching Educators , Children , and Parents ) program is a semi-structured , cognitive-behavioral skills training program that provides teachers with in-classroom consultation on program implementation and classroom-wide behavior management . Data on children 's social skills and behavior problems were collected from parents and teachers at pre- and post-treatment , for 149 children aged 4–5 years ( of whom 56 % were girls ) . Significant treatment effects were found for teacher but not parent reports , with treatment group children improving significantly more than comparison group children in their teacher-rated social skills and internalizing and externalizing problems . These results provide some preliminary support for the efficacy of the program on children 's social skills and behavior problems , and for a teacher-consultation model for training teachers to implement school-based mental health programs Background There is an urgent need for effective , affordable interventions to prevent child mental health problems in low- and middle-income countries . Aims To determine the effects of a universal pre-school-based intervention on child conduct problems and social skills at school and at home . Method In a cluster r and omised design , 24 community pre-schools in inner-city areas of Kingston , Jamaica , were r and omly assigned to receive the Incredible Years Teacher Training intervention ( n = 12 ) or to a control group ( n = 12 ) . Three children from each class with the highest levels of teacher-reported conduct problems were selected for evaluation , giving 225 children aged 3–6 years . The primary outcome was observed child behaviour at school . Secondary outcomes were child behaviour by parent and teacher report , child attendance and parents ’ attitude to school . The study is registered as IS RCT N35476268 . Results Children in intervention schools showed significantly reduced conduct problems ( effect size ( ES ) = 0.42 ) and increased friendship skills ( ES = 0.74 ) through observation , significant reductions to teacher-reported ( ES = 0.47 ) and parent-reported ( ES = 0.22 ) behaviour difficulties and increases in teacher-reported social skills ( ES = 0.59 ) and child attendance ( ES = 0.30 ) . Benefits to parents ’ attitude to school were not significant . Conclusions A low-cost , school-based intervention in a middle-income country substantially reduces child conduct problems and increases child social skills at home and at school This study applied the distillation and matching model to 322 r and omized clinical trials for child mental health treatments . The model involved initial data reduction of 615 treatment protocol descriptions by means of a set of codes describing discrete clinical strategies , referred to as practice elements . Practice elements were then summarized in profiles , which were empirically matched to client factors ( i.e. , observed problem , age , gender , and ethnicity ) . Results of a profile similarity analysis demonstrated a branching of the literature into multiple problem areas , within which some age and ethnicity special cases emerged as higher order splits . This is the 1st study to aggregate evidence -based treatment protocol s empirically according to their constituent treatment procedures , and the results point both to the overall organization of therapy procedures according to matching factors and to gaps in the current child and adolescent treatment literature Separate studies of rural and urban Head Start systems tested the hypothesis that an emotion-based prevention program ( EBP ) would accelerate the development of emotion and social competence and decrease agonistic behavior and potential precursors of psychopathology . In both studies , Head Start centers were r and omly assigned to treatment and control/comparison group conditions . In Study 1 ( rural community ) , results of hierarchical linear modeling analyses showed that compared to the control condition ( Head Start as usual ) , EBP produced greater increases in emotion knowledge and emotion regulation and greater decreases in children 's negative emotion expressions , aggression , anxious/depressed behavior , and negative peer and adult interactions . In Study 2 ( inner city ) , compared to the established prevention program I Can Problem Solve , EBP led to greater increases in emotion knowledge , emotion regulation , positive emotion expression , and social competence . In Study 2 , emotion knowledge mediated the effects of EBP on emotion regulation , and emotion competence ( an aggregate of emotion knowledge and emotion regulation ) mediated the effects of EBP on social competence This r and omized controlled trial ( RCT ) evaluated the efficacy of the Incredible Years ( IY ) Teacher Classroom Management ( TCM ; Webster-Stratton & Reid , 2002 ) program to assess whether training teachers in IY-TCM principles improve teacher behavior , whether any observed improvements impact pupil behavior classroom-wide , and whether these effects can be demonstrated with children at risk of developing conduct problems . Six intervention and six control classrooms comprising 12 teachers and 107 children ( aged 3 to 7years ) were recruited . Children were screened for high or low behavior problems using the cut-off points of the teacher-rated Strengths and Difficulties Question naire ( Goodman , 1997 ) . The primary outcome measure was independent classroom observations using the Teacher-Pupil Observation Tool ( Martin et al. , 2010 ) . Multilevel modeling analyses were conducted to examine the effect of the intervention on teacher , classroom , and child behavior . Results showed a significant reduction in classroom off-task behavior ( d=0.53 ) , teacher negatives to target children ( d=0.36 ) , target child negatives towards the teacher ( d=0.42 ) , and target child off-task behavior ( d=0.48 ) . These preliminary results demonstrate the potential impact of IY-TCM on both teacher and child behavior This paper reports the results from a r and omized clinical trial evaluating an adaptation of the Promoting Alternative Thinking Strategies curriculum ( PATHS ) for preschool-age children in Head Start . PATHS is a universal , teacher-taught social-emotional curriculum that is design ed to improve children ’s social competence and reduce problem behavior . Twenty classrooms in two Pennsylvania communities participated in the study . Teachers in the 10 intervention classrooms implemented weekly lessons and extension activities across a 9-month period . Child assessment s and teacher and parent reports of child behavior assessment s were collected at the beginning and end of the school year . Analysis of covariance was used to control for baseline differences between the groups and pretest scores on each of the outcome measures . The results suggest that after exposure to PATHS , intervention children had higher emotion knowledge skills and were rated by parents and teachers as more socially competent compared to peers . Further , teachers rated intervention children as less socially withdrawn at the end of the school year compared to controls . Editors ’ Strategic Implication s : n Findings from this and other r and omized clinical trials confirm that the Preschool PATHS program is clearly a promising practice for improving children ’s social and emotional competence . Head Start and school programs will find these multi-informant data to be of interest as they consider a curriculum to help prepare children for school entry Behavior problems among preschool children are common . They are important targets for intervention because early externalizing problems and self-regulation issues tend to persist without appropriate attention , and can affect later mental health and school achievement outcomes . However , few preschool curricula addressing social and emotional development exist , and evidence for effects are mixed . In this study , the Second Step Pre/Kindergarten Social and Emotional Learning curriculum was adapted and tested in a small cluster r and omized pilot study of community preschool classrooms to determine if it could improve outcomes in : ( 1 ) individual children ’s teacher-rated behavior problems and prosocial skills ; ( 2 ) classroom climate ( classroom interactions and two measures of disruptive behavior ) ; and ( 3 ) teacher interaction skills . Year 1 outcomes were modest and were accounted for by baseline differences . In Year 2 , classroom climate , measured by independent observers , differed significantly in intervention classrooms , largely because of declines in control classrooms , and there was some evidence for better teacher interaction skills in intervention classrooms . The pattern of effects suggests important impacts on classroom quality worth investigating in a larger study . Both fidelity and implementation rates , as well as positive teacher responses to the curriculum , indicate potential for widespread adoption The present study evaluated the efficacy of a multicomponent , classroom-based intervention in reducing preschoolers ' behavior problems . The Chicago School Readiness Project model was implemented in 35 Head Start classrooms using a clustered-r and omized controlled trial design . Results indicate significant treatment effects ( ds = 0.53 - 0.89 ) for teacher-reported and independent observations of children 's internalizing and externalizing behavior problems . Moreover , there was some evidence for the moderating role of child gender , race/ethnic group membership , and exposure to poverty-related risk , with stronger effects of intervention for some groups of children than for others . Findings contribute to a growing area of research on poverty and preventive intervention in early childhood Children with behavioral , emotional or language problems struggle to do well at school often with limited success . ABLE ( Attention , Behavior , Language , and Emotions ) , a new screening tool , was used to estimate the prevalence and the severity of concerns parents and teachers have about children 's school adjustment and evaluate their need for services . Data obtained from the parents and teachers of children r and omly selected from public Pre-K classrooms in 6 states ( N = 415 ) and from a mental health screening of rural and urban children ( N = 5,577 ) support the validity and reliability of ABLE . Parents identified severe problems in 18.4 % of children and Pre-K teachers identified 10.5 % . By kindergarten , the proportion of children identified by their teachers with serious problems more than doubled to 23 % . Inattention/overactivity and behavior problems were identified most often . These children were 3.4 times more likely to be certified later for special education services by kindergarten than children not identified with problems by ABLE . However , fewer than 14 % of children in public Pre-K identified with serious problems in Pre-K had received mental health services by the end of Kindergarten Families of 159 , 4- to 8-year-old children with oppositional defiant disorder ( ODD ) were r and omly assigned to parent training ( PT ) ; parent plus teacher training ( PT + TT ) ; child training ( CT ) ; child plus teacher training ( CT + TT ) ; parent , child , plus teacher training ( PT + CT + TT ) ; or a waiting list control . Reports and independent observations were collected at home and school . Following the 6-month intervention , all treatments result ed in significantly fewer conduct problems with mothers , teachers , and peers compared to controls . Children 's negative behavior with fathers was lower in the 3 PT conditions than in control . Children showed more prosocial skills with peers in the CT conditions than in control . All PT conditions result ed in less negative and more positive Output:	We discuss implication s that the identification of these practice elements found in the early childhood literature has for efforts to implement models and practice
MS22148	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Aims : Assess the efficacy and safety of saxagliptin added to a submaximal sulphonylurea dose vs. uptitration of sulphonylurea monotherapy in patients with type 2 diabetes and inadequate glycaemic control with sulphonylurea monotherapy . Methods and patients : A total of 768 patients ( 18–77 years ; HbA1c screening ≥ 7.5 to ≤ 10.0 % ) were r and omised and treated with saxagliptin 2.5 or 5 mg in combination with glyburide 7.5 mg vs. glyburide 10 mg for 24 weeks . Blinded uptitration glyburide was allowed in the glyburide-only arm to a maximum total daily dose of 15 mg . Efficacy analyses were performed using ANCOVA and last-observation-carried-forward methodology . Results : At week 24 , 92 % of glyburide-only patients were uptitrated to a total glyburide dose of 15 mg/day . Saxagliptin 2.5 and 5 mg provided statistically significant adjusted mean decreases from baseline to week 24 vs. uptitrated glyburide , respectively , in HbA1c ( −0.54 % , −0.64 % vs. + 0.08 % ; both p < 0.0001 ) and fasting plasma glucose ( −7 , −10 vs. + 1 mg/dl ; p = 0.0218 and p = 0.002 ) . The proportion of patients achieving an HbA1c < 7 % was greater for saxagliptin 2.5 and 5 mg vs. uptitrated glyburide ( 22.4 % and 22.8 % vs. 9.1 % ; both p < 0.0001 ) . Postpr and ial glucose area under the curve was reduced for saxagliptin 2.5 and 5 mg vs. uptitrated glyburide ( −4296 and −5000 vs. + 1196 mg·min/dl ; both p < 0.0001 ) . Adverse event occurrence was similar across all groups . Reported hypoglycaemic events were not statistically significantly different for saxagliptin 2.5 ( 13.3 % ) and 5 mg ( 14.6 % ) vs. uptitrated glyburide ( 10.1 % ) . Conclusion : Saxagliptin added to submaximal glyburide therapy led to statistically significant improvements vs. uptitration of glyburide alone across key glycaemic parameters and was generally well tolerated AIMS To investigate the efficacy and safety of linagliptin , a dipeptidyl peptidase-4 inhibitor , in type 2 diabetes mellitus ( T2DM ) patients for whom metformin was inappropriate . METHODS This 1-year double-blind study ( Clinical Trials.gov , NCT00740051 ) enrolled T2DM patients with inadequate glycaemic control , treatment-naïve [ glycated haemoglobin ( HbA1c ) 7.0 - 10.0 % ] or previously treated with one oral antidiabetes drug ( HbA1c 6.5 - 9.0 % before washout ) , ineligible for metformin because of contraindications ( e.g. renal impairment ) or previous intolerable side effects . Patients were r and omized to monotherapy with linagliptin 5 mg once daily ( n = 151 ) or placebo ( n = 76 ) for 18 weeks , after which placebo patients switched to glimepiride 1 - 4 mg once daily and treatments continued for another 34 weeks . The primary endpoint was change from baseline in HbA1c after 18 weeks ( full- analysis set , last observation carried forward ) . RESULTS At week 18 , adjusted mean difference in change from baseline HbA1c ( 8.1 % ) was -0.60 % ( 95 % confidence interval -0.88 , -0.32 ; p < 0.0001 ) ( -0.39 % with linagliptin , + 0.21 % with placebo ) . At week 52 , mean HbA1c was decreased from baseline in both groups [ linagliptin : -0.44 % ; placebo/glimepiride : -0.72 % ( observed cases ) ] . Adverse events occurred in 40.4 and 48.7 % of linagliptin and placebo patients , respectively , during the initial 18 weeks . During the 34-week extension , patients receiving linagliptin experienced less hypoglycaemia ( 2.2 % vs. 7.8 % ) and no weight gain ( mean change from baseline of -0.2 and + 1.3 kg , respectively ) compared with glimepiride patients . CONCLUSIONS In T2DM patients for whom metformin was inappropriate , linagliptin improved glycaemic control and was well tolerated , with less hypoglycaemia and relative weight loss compared with glimepiride Aims To investigate the efficacy and safety of the dipeptidyl peptidase-4 inhibitor linagliptin in patients with Type 2 diabetes mellitus inadequately controlled by a combination of metformin and pioglitazone . Methods This was a multi-centre , phase 3 , r and omized , double-blind , placebo-controlled study comparing linagliptin 5 mg once daily ( n = 183 ) and placebo ( n = 89 ) as add-on to metformin and pioglitazone . The primary endpoint was the change from baseline in glycated haemoglobin ( HbA1c ) after 24 weeks . Results The placebo-corrected adjusted mean ( se ) change in HbA1c from baseline to 24 weeks was –6 ( 1 ) mmol/mol [ –0.57 (0.13)% ] ( P < 0.0001 ) . In patients with baseline HbA1c ≥ 53 mmol/mol ( 7.0 % ) , 32.4 % of patients in the linagliptin group and 13.8 % in the placebo group achieved HbA1c < 53 mmol/mol ( 7.0 % ) ( odds ratio 2.94 ; P = 0.0033 ) . The placebo-corrected adjusted mean ( se ) change from baseline in fasting plasma glucose at week 24 was –0.57 ( 0.26 ) mmol/l [ –10.4 ( 4.7 ) mg/dl ] ( P = 0.0280 ) . The incidence of serious adverse events was 2.2 % with linagliptin and 3.4 % with placebo . Investigator-defined hypoglycaemia occurred in 5.5 % of the linagliptin group and 5.6 % of the placebo group . No meaningful changes in mean body weight were noted for either group . Conclusions Linagliptin as add-on therapy to metformin and pioglitazone produced significant and clinical ly meaningful improvements in glycaemic control , without an additional risk of hypoglycaemia or weight gain ( Clinical Trials Registry No : NCT 00996658 ) AIM To assess the safety and efficacy of the potent and selective dipeptidyl peptidase-4 inhibitor linagliptin 5 mg when given for 24 weeks to patients with type 2 diabetes who were either treatment-naive or who had received one oral antidiabetes drug ( OAD ) . METHODS This multicentre , r and omized , parallel group , phase III study compared linagliptin treatment ( 5 mg once daily , n = 336 ) with placebo ( n = 167 ) for 24 weeks in type 2 diabetes patients . Before r and omization , patients pretreated with one OAD underwent a washout period of 6 weeks , which included a placebo run-in period during the last 2 weeks . Patients previously untreated with an OAD underwent a 2-week placebo run-in period . The primary endpoint was the change in HbA1c from baseline after 24 weeks of treatment . RESULTS Linagliptin treatment result ed in a placebo-corrected change in HbA1c from baseline of -0.69 % ( p < 0.0001 ) at 24 weeks . In patients with baseline HbA1c ≥ 9.0 % , the adjusted reduction in HbA1c was 1.01 % ( p < 0.0001 ) . Patients treated with linagliptin were more likely to achieve a reduction in HbA1c of ≥0.5 % at 24 weeks than those in the placebo arm ( 47.1 and 19.0 % , respectively ; odds ratio , OR = 4.2 , p < 0.0001 ) . Fasting plasma glucose improved by -1.3 mmol/l ( p < 0.0001 ) with linagliptin vs. placebo , and linagliptin produced an adjusted mean reduction from baseline after 24 weeks in 2-h postpr and ial glucose of -3.2 mmol/l ( p < 0.0001 ) . Statistically significant and relevant treatment differences were observed for proinsulin/insulin ratio ( p = 0.025 ) , Homeostasis Model Assessment -%B ( p = 0.049 ) and disposition index ( p = 0.0005 ) . There was no excess of hypoglycaemic episodes with linagliptin vs. placebo and no patient required third-party intervention . Mild or moderate renal impairment did not influence the trough plasma levels of linagliptin . CONCLUSIONS Monotherapy with linagliptin produced a significant , clinical ly meaningful and sustained improvement in glycaemic control , accompanied by enhanced parameters of β-cell function . The safety profile of linagliptin was comparable with that of placebo Abstract Aims / Introduction The efficacy and safety of sitagliptin , a highly selective dipeptidyl peptidase‐4 inhibitor , when added to metformin monotherapy was examined in Japanese patients with type 2 diabetes . Material s and Methods In this 52‐week , add‐on to metformin study , 149 patients were r and omly assigned to receive sitagliptin 50 mg or placebo once daily in a double‐blind fashion for 12 weeks . Thereafter , all patients who completed the double‐blind period of the study received open‐label sitagliptin 50 mg once daily for 40 weeks , with the investigator option of increasing sitagliptin to 100 mg once daily for patients who met predefined glycemic thresholds . Results After 12 weeks of treatment , the mean change from baseline in glycated hemoglobin ( HbA1c ) significantly decreased with sitagliptin relative to placebo ( between‐group difference [ 95 % confidence interval ] = −0.7 % [ −0.9 to −0.5 ] P < 0.001 ) . At week 12 , the mean changes in 2‐h post‐meal glucose ( −2.6 mmol/L [ −3.5 to −1.7 ] ) and fasting plasma glucose ( −1.0 mmol/L [ −1.3 to −0.6 ] ) also decreased significantly with sitagliptin relative to placebo ( P < 0.001 for both ) . Significant improvements from baseline in glycemic control were also observed in the open‐label period through to week 52 . There were no differences between treatment groups in the incidence of adverse events ( AEs ) , including hypoglycemia and predefined gastrointestinal AEs ( nausea , vomiting and diarrhea ) during the double‐blind period , with similar findings in the open‐label period . Conclusions Over a period of 52 weeks , the addition of sitagliptin once‐daily to ongoing metformin therapy was efficacious and generally well tolerated in Japanese patients with type 2 diabetes . This trial was registered with Clinical Trials.gov ( no. NCT00363948 ) Background To compare the safety and efficacy of saxagliptin 2.5 mg twice daily ( BID ) versus placebo add-on therapy to metformin immediate release ( IR ) in patients with type 2 diabetes and inadequate glycemic control with metformin alone . Methods This multicenter , 12-week , double-blind , parallel-group trial enrolled adult out patients with type 2 diabetes ( glycated hemoglobin [ HbA1c ] 7.0%–10.0 % ) on stable metformin IR monotherapy ( ≥1500 mg , BID for ≥8 weeks ) . Patients were r and omized to double-blind saxagliptin 2.5 mg BID or placebo added on to metformin IR following a 2-week , single-blind , placebo add-on therapy lead-in period . The primary end point was the change from baseline to week 12 in HbA1c . Key secondary end points included change from baseline to week 12 in fasting plasma glucose ( FPG ) and the proportion of patients achieving HbA1c < 7.0 % or HbA1c ≤ 6.5 % at week 12 . Efficacy was analyzed in all patients who received r and omized study drug with ≥1 postbaseline assessment . Safety was assessed in all treated patients . Results In total , 74 patients were r and omized to double-blind saxagliptin add-on therapy and 86 to placebo add-on therapy . At week 12 , Output:	Additionally , studies in Asian subjects , studies in Japanese subjects , and studies conducted in Japan showed relations when three classifications regarding ethnicity and study regions were applied .
MS22149	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: PURPOSE To evaluate safety and efficacy of combined transarterial chemoembolization ( TACE ) with doxorubicin-eluting beads ( DEB ) and sorafenib in patients with advanced hepatocellular carcinoma ( HCC ) . PATIENTS AND METHODS A prospect i ve single-center phase II study was undertaken involving patients with unresectable HCC . The protocol involved sorafenib 400 mg twice per day combined with DEB-TACE . Safety and response were assessed . Results DEB-TACE in combination with sorafenib was successfully administered in 35 patients : mean age , 63 years ; Child 's A , 89 % ; Barcelona Clinic Liver Cancer stage C , 64 % ; Eastern Cooperative Oncology Group performance status of 0 and 1 , 46 % and 54 % , respectively ; and mean index tumor size , 7.7 cm ( st and ard deviation , ± 4.2 cm ) . Patients underwent 128 cycles of therapy ( sorafenib plus DEB-TACE , 60 cycles ; sorafenib alone , 68 cycles ) . Median number of cycles per patient was two ( range , one to five cycles ) ; median number of days treated with sorafenib was 71 ( range , 4 to 620 days ) . The most common toxicities during cycle one were fatigue ( 94 % ) , anorexia ( 67 % ) , alterations in liver enzymes ( 64 % ) , and dermatologic adverse effects ( 48 % ) . Although most patients experienced at least one grade 3 to 4 toxicity , most toxicities were minor ( grade 1 to 2 , 83 % v grade 3 to 4 , 17 % ) . Toxicity during cycle two was decreased . Over the course of the study , there were 40 sorafenib dose interruptions and 25 sorafenib dose reductions . Sorafenib plus DEB-TACE was associated with a disease control rate of 95 % ( Response Evaluation Criteria in Solid Tumors Group)/100 % ( European Association for the Study of the Liver [ EASL ] ) , with an objective response of 58 % ( EASL ) . CONCLUSION The combination of sorafenib and DEB-TACE in patients with unresectable HCC is well tolerated and safe , with most toxicities related to sorafenib . Toxicity is manageable with dose adjustment of sorafenib . Preliminary efficacy data are promising Objective : This study was performed to identify clinical predictors for better survival in patients with advanced hepatocellular carcinoma ( HCC ) under sorafenib treatment . Methods : Between December 2007 and January 2010 , 46 patients with advanced HCC were treated with sorafenib until significant tumor progression or intolerable toxicity . We prospect ively collected clinical baseline data as well as data on the incidence and severity of toxic side effects of sorafenib to be correlated with progression-free survival and overall survival ( OS ) , respectively . Results : Only 26.1 % ( n = 12 ) of patients tolerated sorafenib without requiring dose reduction . The most frequent grade 3 toxicities were diarrhea ( 32.6 % ) , h and -foot skin reaction ( 13.0 % ) , fatigue ( 4.3 % ) , and nausea/vomiting ( 2.2 % ) . Eastern Cooperative Oncology Group performance status ( p = 0.034 ) and portal vein infiltration ( p = 0.021 ) significantly correlated with OS . Furthermore , we found a significant correlation between OS and appearance of grade 2 or 3 diarrhea with a median actuarial survival of 11.8 months ( 95 % CI 6.9–16.6 ) compared to 4.2 months in patients with grade 0 or 1 diarrhea ( 95 % CI 0.0–9.1 ; p = 0.009 ) . In contrast , appearance of h and -foot skin reaction did neither correlate with progression-free survival nor with OS . Conclusion : Appearance of grade 2 or 3 diarrhea indicates a better OS of HCC patients undergoing sorafenib treatment BACKGROUND & AIMS Hepatic markers are utilized in many classification systems of patients with hepatocellular carcinoma and , by measuring organ damage and tumor stage , can influence treatment . Moreover , elevated serum concentrations of aminotransferases and alpha-fetoprotein are indicators of poor prognosis in patients with hepatocellular carcinoma . We examined the effects of sorafenib on hepatic markers by performing exploratory subset analyses of the Sorafenib HCC Assessment R and omized Protocol ( SHARP ) trial in patients categorized by baseline concentrations of alanine aminotransferase/aspartate aminotransferase , alpha-fetoprotein , and bilirubin ; and by evaluating the effects of sorafenib on bilirubin concentrations during treatment . METHODS Patients ( n=602 ) were grouped by baseline concentrations of alanine aminotransferase/aspartate aminotransferase ( not significantly elevated , mildly elevated , or moderately elevated ) , alpha-fetoprotein ( normal or elevated ) , and bilirubin ( normal or elevated ) . Bilirubin was measured at baseline and on day 1 of each cycle . RESULTS Patients with elevated baseline concentrations of alanine aminotransferase/aspartate aminotransferase , alpha-fetoprotein , or bilirubin had shorter overall survival ( OS ) than those with normal baseline concentrations , irrespective of treatment group . No notable differences in safety profiles were observed between patients with normal vs. elevated alanine aminotransferase/aspartate aminotransferase , alpha-fetoprotein , or bilirubin . Median changes from baseline in bilirubin concentration at the last cycle of treatment were + 0.17 and + 0.19 mg/dl in the sorafenib and placebo groups , respectively . CONCLUSIONS These subset analyses suggest that sorafenib is safe and effective for hepatocellular carcinoma , irrespective of baseline alanine aminotransferase/aspartate aminotransferase , alpha-fetoprotein , or bilirubin concentration and that hepatic function remains stable over the course of sorafenib therapy Purpose : Hypertension is a mechanism-based toxicity of sorafenib and other cancer therapeutics that inhibit the vascular endothelial growth factor ( VEGF ) signaling pathway . This prospect i ve , single-center , cohort study characterized ambulatory blood pressure monitoring as an early pharmacodynamic biomarker of VEGF signaling pathway inhibition by sorafenib . Experimental Design : Fifty-four normotensive advanced cancer patients underwent 24-hour ambulatory blood pressure monitoring before and between days 6 and 10 of sorafenib therapy . After blood pressure changes were detected among the first cohort within 10 days , ambulatory blood pressure monitoring was done during the first 24 hours of treatment for the second cohort . Results : For the entire patient population , the blood pressure increase [ mean systolic , + 10.8 mm Hg ; 95 % confidence interval ( 95 % CI ) , 8.6 - 13.0 ; range , −5.2 to + 28.7 mm Hg ; mean diastolic , + 8.0 mm Hg ; 95 % CI , 6.3 - 9.7 ; range , −4.4 to + 27.1 mm Hg ] was detected between days 6 and 10 ( P < 0.0001 for both ) and plateaued thereafter . Variability in blood pressure change did not associate with : age , body size , sex , self-reported race , baseline blood pressure , or steady-state sorafenib plasma concentrations . In the second cohort , the blood pressure elevation was detected during the first 24 hours ( mean systolic , + 8.2 mm Hg ; 95 % CI , 5.0 - 11.3 ; mean diastolic , + 6.5 mm Hg ; 95 % CI , 4.7 - 8.3 ; P < 0.0001 for both ) . Conclusions : Ambulatory blood pressure monitoring detects the blood pressure response to VEGF signaling pathway inhibition by sorafenib during the first 24 hours of treatment . The magnitude of blood pressure elevation is highly variable and unpredictable but could be important in optimizing the therapeutic index of VEGF signaling pathway inhibitor therapy . ( Clin Cancer Res 2009;15(19):6250–7 PURPOSE Sorafenib has been found to have significant clinical activity against hepatocellular carcinoma ( HCC ) . H and -foot skin syndrome ( HFS ) has been described with the usage of sorafenib . It is a dose-limiting toxicity and may lead to compromised efficacy because of dose reduction . METHODS From 14 patients diagnosed with HCC 10 who developed HFS while on treatment with sorafenib were included in this study . Sorafenib was administered orally at a dose of 400 mg twice daily vitamin E usage can be effective in HFS due to sorafenib , therefore vitamin E 300 mg/day was started when HFS occurred . HFS was grade d according to the National Cancer Institute ( NCI ) criteria . RESULTS Grade 2 - 3 HFS was found in 10 of 14 patients . Vitamin E was started to all patients without using topical agents . Mean time to the appearance of HFS was 15 ± 3 days ( range 10 - 22 ) after starting sorafenib . Grade was 3 in 4 patients , 2 in 4 patients and 1 in 2 patients . Vitamin E administration had a marked effect after 10 - 12 days of its initiation . Skin lesions disappeared without any dose modification . CONCLUSION Sorafenib is the gold st and ard for HCC treatment . Dose modification due to HFS decreases the effectiveness of this agent . Adding vitamin E to sorafenib is effective in HFS without dose reduction or treatment interruption . This is the first clinical study to report resolution of HFS with vitamin E due to sorafenib therapy BACKGROUND In Japan and South Korea , transarterial chemoembolisation ( TACE ) is an important locoregional treatment for patients with unresectable hepatocellular carcinoma ( HCC ) . Sorafenib , a multikinase inhibitor , has been shown effective and safe in patients with advanced HCC . This phase III trial assessed the efficacy and safety of sorafenib in Japanese and Korean patients with unresectable HCC who responded to TACE . METHODS Patients ( n=458 ) with unresectable HCC , Child-Pugh class A cirrhosis and ≥25 % tumour necrosis/shrinkage 1 - 3 months after 1 or 2 TACE sessions were r and omised 1:1 to sorafenib 400 mg bid or placebo and treated until progression/recurrence or unacceptable toxicity . Primary end-point was time to progression/recurrence ( TTP ) . Secondary end-point was overall survival ( OS ) . FINDINGS Baseline characteristics in the two groups were similar ; > 50 % of patients started sorafenib>9 weeks after TACE . Median TTP in the sorafenib and placebo groups was 5.4 and 3.7 months , respectively ( hazard ratio ( HR ) , 0.87 ; 95 % confidence interval ( CI ) , 0.70 - 1.09 ; P=0.252 ) . HR ( sorafenib/placebo ) for OS was 1.06 ( 95 % CI , 0.69 - 1.64 ; P=0.790 ) . Median daily dose of sorafenib was 386 mg , with 73 % of patients having dose reductions and 91 % having dose interruptions . Median administration of sorafenib and placebo was 17.1 and 20.1 weeks , respectively . No unexpected adverse events were observed . INTERPRETATION This trial , conducted prior to the reporting of registration al phase III trials , found that sorafenib did not significantly prolong TTP in patients who responded to TACE . This may have been due to delays in starting sorafenib after TACE and /or low daily sorafenib doses BACKGROUND We conducted a phase 3 , r and omized , double-blind , placebo-controlled trial of sorafenib , a multikinase inhibitor of tumor-cell proliferation and angiogenesis , in patients with advanced clear-cell renal-cell carcinoma . METHODS From November 2003 to March 2005 , we r and omly assigned 903 patients with renal-cell carcinoma that was resistant to st and ard therapy to receive either continuous treatment with oral sorafenib ( at a dose of 400 mg twice daily ) or placebo ; 451 patients received sorafenib and 452 received placebo . The primary end point was overall survival . A single planned analysis of progression-free survival in January 2005 showed a statistically significant benefit of sorafenib over placebo . Consequently , crossover was permitted from placebo to sorafenib , beginning in May 2005 . RESULTS At the January 2005 cutoff , the median progression-free survival was 5.5 months in the sorafenib group and 2.8 months in the placebo group ( hazard ratio for disease progression in the sorafenib group , 0.44 ; 95 % confidence interval [ CI ] , 0.35 to 0.55 ; P<0.01 ) . The first interim analysis of overall survival in May 2005 showed that sorafenib reduced the risk of death , as compared with placebo ( hazard ratio , 0.72 ; 95 % CI , 0.54 to 0 Output:	Sorafenib was associated with a higher risk of adverse effects than placebo . The risk for grade 3 - 4 h and -foot skin reactions , rash or desquamation , diarrhea , and hypertension was much higher in the sorafenib treatment group . These side effects could often be mitigated with appropriate treatment . CONCLUSIONS Sorafenib was a moderately effective and safe oral drug for use in Child-Pugh A patients with unresectable HCC . Sorafenib monotherapy is not recommended for treating intermediate-stage HCC .
MS22150	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: & NA ; Myofascial trigger points ( TrPs ) have been clinical ly described as discrete areas of muscle tenderness presenting in taut b and s of skeletal muscle . Using well‐defined clinical criteria , prior investigations have demonstrated interrater reliability in the diagnosis of TrPs within a given muscle . No reports exist , however , with respect to the precision with which experienced clinicians can determine the anatomic locations of TrPs within a muscle . This paper details a study wherein four trained clinicians achieved statistically significant reliability ( see below ) in estimating the precise locations of latent TrPs in the trapezius muscle of volunteer subjects ( n=20 ) . To do so , the clinicians trained extensively together prior to the study . The precise anatomic location of each subject 's primary TrP was measured in a blinded fashion using a 3 dimensional ( 3‐D ) camera system . Use of this measurement system permitted the anatomic co‐ordinates of each TrP to be located without providing feedback to subsequent clinicians . The clinicians each used a pressure algometer along with patient feedback to document the sensitivity of each suspected TrP site , however unlike routine clinical practice , the algometry was performed with a double‐blinded approach hence the results were only examined post‐hoc . At the time of data collection ( algometry readings unknown ) , 16 of the 20 subjects were judged to present with a latent TrP. Subsequently , when subjected to a criterion pressure threshold value of < 3.0 kg.cm−2 , 12 of these TrPs were classified as being clinical ly sensitive . To assess the 3‐D measurement precision , and the reliability of the TrP estimates , statistical measures of the SEM and the Generalizability coefficient ( G‐coeff ) were determined for all suspected TrP sites in the superior‐inferior , medial‐lateral and anterior‐posterior directions . The best results were determined by pooling the measurements of all 4 clinicians , however , based upon exceeding a criterion reliability threshold of 80 % , the use of just two testers was found to produce reliable results . The two‐tester condition yielded a precision of 7.5 , 7.6 and 6.5 mm ( SEM ) with reliability ( G‐coeff ) of 0.92 , 0.86 and 0.83 , respectively . Given the double‐blinded methodology , the use of pressure algometry was also found to demonstrate internal validity . The algometer responses associated with TrP estimates varied inversely with respect to the clinical group 's reliability in identify the TrP locations . To summarize , for the trapezius muscle , this study demonstrates that two trained examiners can reliably localize latent TrPs with a precision that essentially approaches the physical dimensions of the clinician 's own fingertips . Finally , it should be recognized that the ability to precisely document TrP location appears critical to the success of future studies that may be design ed to investigate the etiology and pathogenesis of this commonly diagnosed clinical disorder OBJECTIVE To test the hypothesis that dry needle stimulation of a myofascial trigger point ( sensitive locus ) evokes segmental anti-nociceptive effects . DESIGN Double-blind r and omized controlled trial . SUBJECTS Forty subjects ( 21 males , 19 females ) . METHODS Test subjects received intramuscular dry needle puncture to a right supraspinatus trigger point ( C4,5 ) ; controls received sham intramuscular dry needle puncture . Pain pressure threshold ( PPT ) readings were recorded from right infraspinatus ( C5,6 ) and right gluteus medius ( L4,5S1 ) trigger points at 0 ( pre-needling baseline ) , 1 , 3 , 5 , 10 and 15 min post-needling and normalized to baseline values . The supraspinatus and infraspinatus trigger points are neurologically linked at C5 ; the supraspinatus and gluteus medius are segmentally unrelated . The difference between the infraspinatus and gluteus medius PPT values ( PPTseg ) represents a direct measure of the segmental anti-nociceptive effects acting at the infraspinatus trigger point . RESULTS Significant increases in PPTseg were observed in test subjects at 3 ( p = 0.002 ) and 5 ( p = 0.015 ) min post-needling , compared with controls . CONCLUSION One intervention of dry needle stimulation to a single trigger point ( sensitive locus ) evokes short-term segmental anti-nociceptive effects . These results suggest that trigger point ( sensitive locus ) stimulation may evoke anti-nociceptive effects by modulating segmental mechanisms , which may be an important consideration in the management of myofascial pain OBJECTIVES To determine the interexaminer reliability of palpation of three characteristics of trigger points ( taut b and , local twitch response , and referred pain ) in patients with subacute low back pain , to determine whether training in palpation would improve reliability , and whether there was a difference between the physiatric and chiropractic physicians . DESIGN Reliability study . SETTING Whittier Health Campus , Los Angeles College of Chiropractic . PARTICIPANTS Twenty-six nonsymptomatic individuals and 26 individuals with subacute low back pain . INTERVENTION Twenty muscles per individual were first palpated by an expert and then r and omly by four physician examiners . MAIN OUTCOME MEASURES Palpation findings . RESULTS Kappa scores for palpation of taut b and s , local twitch responses , and referred pain were .215 , .123 , and .342 , respectively , between the expert and the trained examiners , and .050 , .118 , and .326 , respectively , between the expert and the untrained examiners . Kappa scores for agreement for palpation of taut b and s , twitch responses , and referred pain were .108 , -.001 , and .435 , respectively , among the nonexpert , trained examiners , and -.019 , .022 , and .320 , respectively , among the nonexpert , untrained examiners . CONCLUSIONS Among nonexpert physicians , physiatric or chiropractic , trigger point palpation is not reliable for detecting taut b and and local twitch response , and only marginally reliable for referred pain after training The presence of a trigger point is essential to the myofascial pain syndrome . This study centres on identifying clearer criteria for the presence of trigger points in the quadratus lumborum and gluteus medius muscle by investigating the occurrence and inter-rater reliability of trigger point symptoms . Using the symptoms and signs as described by Simons ' 1990 definition and two other former sets of criteria , 61 non-specific low back pain patients and 63 controls were examined in general practice by 5 observers , working in pairs . From the two major criteria of Simons ' 1990 definition only ' localized tenderness ' has good discriminative ability and inter-rater reliability ( kappa > 0.5 ) . This study does not find proof for the clinical usefulness of ' referred pain ' , which has neither of these two abilities . The criteria ' jump sign ' and ' recognition ' , on the condition that localized tenderness is present , also have good discriminative ability and inter-rater reliability . Trigger points defined by the criteria found eligible in this study allow significant distinction between non-specific low back pain patients and controls . This is not the case with trigger points defined by Simons ' 1990 criteria . Concerning reliability there is also a significant difference between the two different criteria sets . This study suggests that the clinical usefulness of trigger points is increased when localized tenderness and the presence of either jump sign or patient 's recognition of his pain complaint are used as criteria for the presence of trigger points in the M. quadratus lumborum and the M. gluteus medius Objectives : To investigate the test-retest reliability of the following clinical diagnostic characteristics of myofascial trigger points : taut b and , spot tenderness , jump sign , pain recognition , referred pain and local twitch responses ( LTRs ) . Design : Test-retest reliability study . Setting : This study was undertaken in an outpatient physiotherapy department . Subjects : Fifty-eight patients ( 31 males and 27 females ) with rotator cuff tendonitis were recruited into this study . Intervention : Rotator cuff muscles were assessed by an expert for the presence or absence of the main clinical diagnostic characteristics of trigger point assessment . The process was then repeated three days later by the same expert . Main measures : Outcomes included the presence or absence of : a taut b and , spot tenderness , jump sign , pain recognition , referred pain and LTRs . Results : Kappa values between testing situations for the taut b and , spot tenderness , jump sign and pain recognition were 1 . Kappa scores for referred pain ranged between 0.79 and 0.88 and for the local twitch response between 0.75 and 1 depending on the muscles under investigation . Conclusions : The presence or absence of the taut b and , spot tenderness , jump sign and pain recognition was highly reliable between sessions . Referred pain and local twitch response reliability varied depending on the muscle being studied OBJECTIVE The purpose of this study was to investigate if spinal manipulative therapy ( SMT ) can evoke immediate regional antinociceptive effects in myofascial tissues by increasing pressure pain thresholds ( PPTs ) over myofascial trigger points in healthy young adults . METHODS A total of 36 participants ( 19 men , 17 women ; age , 28.0 [ 5.3 ] years ; body mass index , 26.5 [ 5.7 ] kg/m(2 ) ) with clinical ly identifiable myofascial trigger points in the infraspinatus and gluteus medius muscles were recruited from the University of Guelph , Ontario , Canada . Participants were r and omly allocated to 2 groups . Participants in the test group received chiropractic SMT targeted to the C5-C6 spinal segment . Participants in the control group received sham SMT . The PPT was recorded from the right infraspinatus and gluteus medius muscles at baseline ( preintervention ) and 1 , 5 , 10 , and 15 minutes postintervention . RESULTS Three participants were disqualified , result ing in a total of 33 participants analyzed . Significant increases in the PPT ( decreased pain sensitivity ) were observed in the test infraspinatus group when compared with test gluteus medius , control infraspinatus , and control gluteus medius groups ( P < .05 ) . No significant differences in PPT were observed at any time point when comparing test gluteus medius , control infraspinatus , and control gluteus medius groups ( P > .05 ) . CONCLUSIONS This study showed that SMT evokes short-term regional increases in PPT within myofascial tissues in healthy young adults Abstract The myofascial trigger point ( MTrP ) is the hallmark physical finding of the myofascial pain syndrome ( MPS ) . The MTrP itself is characterized by distinctive physical features that include a tender point in a taut b and of muscle , a local twitch response ( LTR ) to mechanical stimulation , a pain referral pattern characteristic of trigger points of specific areas in each muscle , and the reproduction of the patient 's usual pain . No prior study has demonstrated that these physical features are reproducible among different examiners , thereby establishing the reliability of the physical examination in the diagnosis of the MPS . This paper reports an initial attempt to establish the interrater reliability of the trigger point examination that failed , and a second study by the same examiners that included a training period and that successfully established interrater reliability in the diagnosis of the MTrP. The study also showed that the interrater reliability of different features varies , the LTR being the most difficult , and that the interrater reliability of the identification of MTrP features among different muscles also varies Objective . Increasing research interest and emerging new therapies for treatment of fibromyalgia ( FM ) have led to a need to develop a consensus on a core set of outcome measures that should be assessed and reported in all clinical trials , to facilitate interpretation of the data and underst and ing of the disease . This aligns with the key objective of the Outcome Measures in Rheumatology ( OMERACT ) initiative to improve outcome measurement through a data driven , interactive consensus process . Methods . Through patient focus groups and Delphi processes , working groups at previous OMERACT meetings identified potential domains to be included in the core data set . A systematic review has shown that instruments measuring these domains are available and are at least moderately sensitive to change . Most instruments have been vali date d in multiple language s. This pooled analysis study aims to develop the core data set by analyzing data from 10 r and omized controlled trials ( RCT ) in FM . Results . Results from this study provide support for the inclusion of the following in the core data set : pain , tenderness , fatigue , sleep , patient global assessment , and multidimensional function/health related quality of life . Construct validity was demonstrated with outcome instruments showing convergent and divergent validity . Content and criterion validity were confirmed by multivariate analysis showing R square values between 0.4 and 0.6 . Low R square value is associated with studies in which one or more domains were not assessed . Conclusion . The core data set was supported by high consensus among attendees at OMERACT 9 . Establishing an international st and ard for RCT in FM should facilitate future metaanalyses and indirect comparisons OBJECTIVE To examine prospect ively the accuracy of an initial diagnosis for fibromyalgia ( FM ) . METHODS All patients newly referred for rheumatology consultation in a 6-month period were evaluated prospect ively for either a preceding , current or subsequent diagnosis of FM . Clinical characteristics , previous and subsequent management and health care utilization were assessed . The final diagnosis at 6 months was verified and accuracy regarding the diagnosis of FM was assessed . RESULTS Seventy six ( 12 % ) of all new patients were either referred with a question of FM or finally diagnosed with FM . At the final evaluation the accuracy of the diagnosis regarding FM by either the referring physician or by the rheumatologist at the time of the initial visit was correct in 34 % of patients . The FM group in comparison with those with some other rhe Output:	Statistically significant improvements in pain and disability were reported within but not between groups . Conclusion Few trials have been conducted study ing thrust manipulation plus another conservative intervention for rotator cuff conditions rendering available evidence of thrust manipulation plus exercise insufficient to determine effects of this combined treatment
MS22151	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Uncertainty exists about the optimal schedule of adjuvant treatment of breast cancer with aromatase inhibitors and , to our knowledge , no trial has directly compared the three aromatase inhibitors anastrozole , exemestane , and letrozole . We investigated the schedule and type of aromatase inhibitors to be used as adjuvant treatment for hormone receptor-positive early breast cancer . METHODS FATA-GIM3 is a multicentre , open-label , r and omised , phase 3 trial of six different treatments in postmenopausal women with hormone receptor-positive early breast cancer . Eligible patients had histologically confirmed invasive hormone receptor-positive breast cancer that had been completely removed by surgery , any pathological tumour size , and axillary nodal status . Key exclusion criteria were hormone replacement therapy , recurrent or metastatic disease , previous treatment with tamoxifen , and another malignancy in the previous 10 years . Patients were r and omly assigned in an equal ratio to one of six treatment groups : oral anastrozole ( 1 mg per day ) , exemestane ( 25 mg per day ) , or letrozole ( 2·5 mg per day ) tablets upfront for 5 years ( upfront strategy ) or oral tamoxifen ( 20 mg per day ) for 2 years followed by oral administration of one of the three aromatase inhibitors for 3 years ( switch strategy ) . R and omisation was done by a computerised minimisation procedure stratified for oestrogen receptor , progesterone receptor , and HER2 status ; previous chemotherapy ; and pathological nodal status . Neither the patients nor the physicians were masked to treatment allocation . The primary endpoint was disease-free survival . The minimum cutoff to declare superiority of the upfront strategy over the switch strategy was assumed to be a 2 % difference in disease-free survival at 5 years . Primary efficacy analyses were done by intention to treat ; safety analyses included all patients for whom at least one safety case report form had been completed . Follow-up is ongoing . This trial is registered with the European Clinical Trials Data base , number 2006 - 004018 - 42 , and Clinical Trials.gov , number NCT00541086 . FINDINGS Between March 9 , 2007 , and July 31 , 2012 , 3697 patients were enrolled into the study . After a median follow-up of 60 months ( IQR 46 - 72 ) , 401 disease-free survival events were reported , including 211 ( 11 % ) of 1850 patients allocated to the switch strategy and 190 ( 10 % ) of 1847 patients allocated to upfront treatment . 5-year disease-free survival was 88·5 % ( 95 % CI 86·7 - 90·0 ) with the switch strategy and 89·8 % ( 88·2 - 91·2 ) with upfront treatment ( hazard ratio 0·89 , 95 % CI 0·73 - 1·08 ; p=0·23 ) . 5-year disease-free survival was 90·0 % ( 95 % CI 87·9 - 91·7 ) with anastrozole ( 124 events ) , 88·0 % ( 85·8 - 89·9 ) with exemestane ( 148 events ) , and 89·4 % ( 87·3 to 91·1 ) with letrozole ( 129 events ; p=0·24 ) . No unexpected serious adverse reactions or treatment-related deaths occurred . Musculoskeletal side-effects were the most frequent grade 3 - 4 events , reported in 130 ( 7 % ) of 1761 patients who received the switch strategy and 128 ( 7 % ) of 1766 patients who received upfront treatment . Grade 1 musculoskeletal events were more frequent with the upfront schedule than with the switch schedule ( 924 [ 52 % ] of 1766 patients vs 745 [ 42 % ] of 1761 patients ) . All other grade 3 - 4 adverse events occurred in less than 2 % of patients in either group . INTERPRETATION 5 years of treatment with aromatase inhibitors was not superior to 2 years of tamoxifen followed by 3 years of aromatase inhibitors . None of the three aromatase inhibitors was superior to the others in terms of efficacy . Therefore , patient preference , tolerability , and financial constraints should be considered when deciding the optimal treatment approach in this setting . FUNDING Italian Drug Agency Background : The effect of tamoxifen dose elevation on endoxifen serum concentration was investigated in patients with reduced CYP2D6 activity result ing from genetic variation and /or CYP2D6 inhibitor use . Additionally , baseline differences in endoxifen concentrations between the different CYP2D6 phenotypes were studied . Methods : Patients , treated with tamoxifen 20 mg once daily ( QD ) for at least 4 weeks , were classified as phenotypic extensive ( EM ) , intermediate ( IM ) , or poor ( PM ) metabolizer based on their genotype and comedication . In patients with an IM or PM phenotype , the tamoxifen dose was increased to 40 mg QD for 4 weeks . Tamoxifen , 4-OH-tamoxifen , N-desmethyltamoxifen , and endoxifen serum concentrations were measured at baseline and 4 weeks after the dose increment . Side effects of tamoxifen were assessed using the vali date d Functional Assessment of Cancer Therapy – Endocrine Symptom subscale ( FACT-ESS-19 ) . Results : The median baseline endoxifen concentration differed between EMs ( 11.4 mcg/L : n = 19 ) , IMs ( 8.3 mcg/L : n = 16 ) , and PMs ( 4.0 mcg/L : n = 7 ) , P = 0.040 . Tamoxifen dose elevation significantly increased the median endoxifen concentrations in 12 IMs from 9.5 to 17.4 mcg/L ( P < 0.001 ) and in 4 PMs from 3.8 to 7.8 mcg/L ( P = 0.001 ) , without influencing median FACT-ESS-19 scores . Conclusions : Raising the tamoxifen dose to 40 mg QD significantly increased endoxifen concentrations in IMs and PMs without increasing side effects . The tamoxifen dose increment in PMs was insufficient to reach endoxifen concentrations equal to those observed in EMs . Future studies will clarify the direct effect of endoxifen exposure on tamoxifen efficacy and may reveal a threshold endoxifen concentration that is critical for its efficacy PURPOSE Tamoxifen is an effective treatment for metastatic and primary breast cancer and is now being evaluated as a chemoprevention agent in healthy women . Any long-term effects on estrogen-sensitive tissues such as bone may have important therapeutic implication s. METHODS We measured bone mineral density ( BMD ) in the lumbar spine and hip using dual-energy x-ray absorptiometry ( DXA ) in premenopausal and postmenopausal healthy women who participated in our placebo-controlled tamoxifen chemoprevention of breast cancer trial . RESULTS BMD data are now available from 179 women for this analysis . In premenopausal women , BMD decreased progressively in the lumbar spine ( P < .001 ) and in the hip ( P < .05 ) for women on tamoxifen , but not those on placebo . The mean annual loss in lumbar BMD per year over the 3-year study period in tamoxifen-treated compliant women who remained premenopausal throughout the study period was 1.44 % ( 1.88 % calculated on an intent-to-treat basis ) compared with a small gain of 0.24 % per annum for women on placebo ( P < .001 ) . Tamoxifen had the opposite effect in postmenopausal women . The mean annual increase in BMD for women on tamoxifen was 1.17 % in the spine ( P < .005 ) and 1.71 % in the hip ( P < .001 ) compared with a noninsignificant loss for women on placebo . CONCLUSION These results indicate that tamoxifen treatment is associated with a significant loss of BMD in premenopausal women , whereas it prevents bone loss in postmenopausal women . These adverse and beneficial effects of tamoxifen should be considered in the assessment of the therapeutic benefits for both the adjuvant treatment and the chemoprevention of breast cancer BACKGROUND The NSABP B-35 trial compared 5 years of treatment with anastrozole versus tamoxifen for reducing subsequent occurrence of breast cancer in postmenopausal patients with ductal carcinoma in situ . This report assesses the effect of these drugs on quality of life and symptoms . METHODS The study was done at 333 hospitals in North America . Postmenopausal women with hormone-positive ductal carcinoma in situ treated by lumpectomy with clear resection margins and whole breast irradiation were r and omly assigned to receive either tamoxifen ( 20 mg/day ) or anastrazole ( 1 mg/day ) for 5 years , stratified by age ( < 60 years vs ≥60 years ) . Patients and investigators were masked to treatment allocation . Patients completed question naires at baseline and every 6 months thereafter for 6 years . The primary outcomes were SF-12 physical and mental health component scale scores , and vasomotor symptoms ( as per the BCPT symptom scale ) . Secondary outcomes were vaginal symptoms and sexual functioning . Exploratory outcomes were musculoskeletal pain , bladder symptoms , gynaecological symptoms , cognitive symptoms , weight problems , vitality , and depression . We did the analyses by intention to treat , including patients who completed question naires at baseline and at least once during follow-up . This study is registered with Clinical Trials.gov , NCT00053898 . FINDINGS Between Jan 6 , 2003 , and June 15 , 2006 , 3104 patients were enrolled in the study , of whom 1193 were included in the quality -of-life sub study : 601 assigned to tamoxifen and 592 assigned to anastrozole . We detected no significant difference between treatment groups for : physical health scores ( mean severity score 46·72 for tamoxifen vs 45·85 for anastrozole ; p=0·20 ) , mental health scores ( 52·38 vs 51·48 ; p=0·38 ) , energy and fatigue ( 58·34 vs 57·54 ; p=0·86 ) , or symptoms of depression ( 6·19 vs 6·39 ; p=0·46 ) over 5 years . Vasomotor symptoms ( 1·33 vs 1·17 ; p=0·011 ) , difficulty with bladder control ( 0·96 vs 0·80 ; p=0·0002 ) , and gynaecological symptoms ( 0·29 vs 0·18 ; p<0·0001 ) were significantly more severe in the tamoxifen group than in the anastrozole group . Musculoskeletal pain ( 1·50 vs 1·72 ; p=0·0006 ) and vaginal symptoms ( 0·76 vs 0·86 ; p=0·035 ) were significantly worse in the anastrozole group than in the tamoxifen group . Sexual functioning did not differ significantly between the two treatments ( 43·65 vs 45·29 ; p=0·56 ) . Younger age was significantly associated with more severe vasomotor symptoms ( mean severity score 1·45 for age < 60 years vs 0·65 for age ≥60 years ; p=0·0006 ) , vaginal symptoms ( 0·98 vs 0·65 ; p<0·0001 ) , weight problems ( 1·32 vs 1·02 ; p<0·0001 ) , and gynaecological symptoms ( 0·26 vs 0·22 ; p=0·014 ) . INTERPRETATION Given the similar efficacy of tamoxifen and anastrozole for women older than age 60 years , decisions about treatment should be informed by the risk for serious adverse health effects and the symptoms associated with each drug . For women younger than 60 years old , treatment decisions might be driven by efficacy ( favouring anastrozole ) ; however , if the side-effects of anastrozole are intolerable , then switching to tamoxifen is a good alternative . FUNDING US National Cancer Institute , AstraZeneca Pharmaceuticals Summary Because treatment for breast cancer may adversely affect skeletal metabolism , we investigated vertebral fracture risk in women with non-metastatic breast cancer . The prevalence of vertebral fracture was similar in women at the time of first diagnosis to that in an age-matched sample of the general population . The incidence of vertebral fracture , however , was nearly five times greater than normal in women from the time of first diagnosis [ odds ratio ( OR ) , 4.7 ; 95 % confidence interval ( 95 % CI ) , 2.3–9.9 ] , and 20-fold higher in women with soft-tissue metastases without evidence of skeletal metastases ( OR , 22.7 ; 95 % CI , 9.1–57.1 ) . We conclude that vertebral fracture risk is markedly increased in women with breast cancer BACKGROUND Adjuvant tamoxifen therapy is effective for postmenopausal women with endocr Output:	Results Although conflicting literature exists , the majority of the current evidence points toward CYP2D6 genetic variation affecting survival outcomes after tamoxifen treatment . Conclusions and recommendations Critical appraisal of the literature provided evidence for the value of comprehensive CYP2D6 genotyping panels in guiding treatment decisions for non-metastatic ER-positive breast cancer patients .
MS22152	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The ventral tegmental area ( VTA ) has been primarily implicated in reward-motivated behavior . Recently , aberrant dopaminergic VTA signaling has also been implicated in anxiety-like behaviors in animal models . These findings , however , have yet to be extended to anxiety in humans . Here we hypothesized that clinical anxiety is linked to dysfunction of the mesocorticolimbic circuit during threat processing in humans ; specifically , excessive or dysregulated activity of the mesocorticolimbic aversion circuit may be etiologically related to errors in distinguishing cues of threat versus safety , also known as “ overgeneralization of fear . ” To test this , we recruited 32 females with generalized anxiety disorder and 25 age-matched healthy control females . We measured brain activity using fMRI while participants underwent a fear generalization task consisting of pseudo-r and omly presented rectangles with systematic ally varying widths . A mid-sized rectangle served as a conditioned stimulus ( CS ; 50 % electric shock probability ) and rectangles with widths of CS ±20 % , ±40 % , and ±60 % served as generalization stimuli ( GS ; never paired with electric shock ) . Healthy controls showed VTA reactivity proportional to the cue 's perceptual similarity to CS ( threat ) . In contrast , patients with generalized anxiety disorder showed heightened and less discriminating VTA reactivity to GS , a feature that was positively correlated with trait anxiety , as well as increased mesocortical and decreased mesohippocampal coupling . Our results suggest that the human VTA and the mesocorticolimbic system play a crucial role in threat processing , and that abnormalities in this system are implicated in maladaptive threat processing in clinical anxiety The role of worry in generalized anxiety disorder ( GAD ) has been posited to serve as an avoidance of emotional experience , and emotion regulation deficits in GAD have been found in several previous studies . It remains unclear whether those with GAD experience more dysregulated emotions during periods of euthymia and positive affect or whether these deficits occur only during periods of worry . Individuals with GAD ( with and without co-occurring dysphoria ) and non-anxious controls were r and omly assigned to receive a worry , neutral , or relaxation induction . Following the induction , all participants viewed a film clip documented to elicit sadness . Intensity of emotions and emotion regulation were examined following the induction period and film clip . The results revealed that , regardless of co-occurring dysphoria , individuals with GAD in the worry condition experienced more intense depressed affect than GAD participants in the other conditions and controls participants . In contrast , presence of worry appeared to have less impact on indices of emotion dysregulation , which were greater in participants with GAD compared to controls , but largely insensitive to context ual effects of worry or of relaxation . Following film viewing , both GAD participants with and without dysphoria displayed poorer underst and ing , acceptance , and management of emotions than did controls . However , acceptance and management deficits were most pronounced in individuals with both GAD and co-occurring dysphoria . Implication s for the role of emotions in conceptualization and treatment of GAD are discussed Theory of Mind ( ToM ) , the ability to attribute mental states to others , and empathy , the ability to infer emotional experiences , are important processes in social cognition . Brain imaging studies in healthy subjects have described a brain system involving medial prefrontal cortex , superior temporal sulcus and temporal pole in ToM processing . Studies investigating networks associated with empathic responding also suggest involvement of temporal and frontal lobe regions . In this fMRI study , we used a cartoon task derived from Sarfati et al. ( 1997 ) [ Sarfati , Y. , Hardy-Bayle , M.C. , Besche , C. , Widlocher , D. 1997 . Attribution of intentions to others in people with schizophrenia : a non-verbal exploration with comic strips . Schizophrenia Research 25 , 199 - 209.]with both ToM and empathy stimuli in order to allow comparison of brain activations in these two processes . Results of 13 right-h and ed , healthy , male volunteers were included . Functional images were acquired using a 1.5 T Phillips Gyroscan . Our results confirmed that ToM and empathy stimuli are associated with overlapping but distinct neuronal networks . Common areas of activation included the medial prefrontal cortex , temporoparietal junction and temporal poles . Compared to the empathy condition , ToM stimuli revealed increased activations in lateral orbitofrontal cortex , middle frontal gyrus , cuneus and superior temporal gyrus . Empathy , on the other h and , was associated with enhanced activations of paracingulate , anterior and posterior cingulate and amygdala . We therefore suggest that ToM and empathy both rely on networks associated with making inferences about mental states of others . However , empathic responding requires the additional recruitment of networks involved in emotional processing . These results have implication s for our underst and ing of disorders characterized by impairments of social cognition , such as autism and psychopathy As a central fear processor of the brain , the amygdala initiates a cascade of critical physiological and behavioral responses . Neuroimaging studies have shown that the human amygdala responds not only to fearful and angry facial expressions but also to fearful and threatening scenes such as attacks , explosions , and mutilations . Given the relative importance of facial expressions in adaptive social behavior , we hypothesized that the human amygdala would exhibit a stronger response to angry and fearful facial expressions in comparison to other fearful and threatening stimuli . Twelve subjects completed two tasks while undergoing fMRI : matching angry or fearful facial expressions , and matching scenes depicting fearful or threatening situations derived from the International Affective Picture System ( IAPS ) . While there was an amygdala response to both facial expressions and IAPS stimuli , direct comparison revealed that the amygdala response to facial expressions was significantly greater than that to IAPS stimuli . Autonomic reactivity , measured by skin conductance responses , was also greater to facial expressions . These results suggest that the human amygdala shows a stronger response to affective facial expressions than to scenes , a bias that should be considered in the design of experimental paradigms interested in probing amygdala function Mindfulness training aims to impact emotion regulation . Generalized anxiety disorder ( GAD ) symptoms can be successfully addressed through mindfulness-based interventions . This preliminary study is the first to investigate neural mechanisms of symptom improvements in GAD following mindfulness training . Furthermore , we compared brain activation between GAD patients and healthy participants at baseline . 26 patients with a current DSM-IV GAD diagnosis were r and omized to an 8-week Mindfulness Based Stress Reduction ( MBSR , N = 15 ) or a stress management education ( SME , N = 11 ) active control program . 26 healthy participants were included for baseline comparisons . BOLD response was assessed with fMRI during affect labeling of angry and neutral facial expressions . At baseline , GAD patients showed higher amygdala activation than healthy participants in response to neutral , but not angry faces , suggesting that ambiguous stimuli reveal stronger reactivity in GAD patients . In patients , amygdala activation in response to neutral faces decreased following both interventions . BOLD response in ventrolateral prefrontal regions ( VLPFC ) showed greater increase in MBSR than SME participants . Functional connectivity between amygdala and PFC regions increased significantly pre- to post-intervention within the MBSR , but not SME group . Both , change in VLPFC activation and amygdala – prefrontal connectivity were correlated with change in Beck Anxiety Inventory ( BAI ) scores , suggesting clinical relevance of these changes . Amygdala – prefrontal connectivity turned from negative coupling ( typically seen in down-regulation of emotions ) , to positive coupling ; potentially suggesting a unique mechanism of mindfulness . Findings suggest that in GAD , mindfulness training leads to changes in fronto-limbic areas crucial for the regulation of emotion ; these changes correspond with reported symptom improvements BACKGROUND Functional magnetic resonance imaging ( fMRI ) holds promise as a noninvasive means of identifying neural responses that can be used to predict treatment response before beginning a drug trial . Imaging paradigms employing facial expressions as presented stimuli have been shown to activate the amygdala and anterior cingulate cortex ( ACC ) . Here , we sought to determine whether pretreatment amygdala and rostral ACC ( rACC ) reactivity to facial expressions could predict treatment outcomes in patients with generalized anxiety disorder ( GAD ) . METHODS Fifteen subjects ( 12 female subjects ) with GAD participated in an open-label venlafaxine treatment trial . Functional magnetic resonance imaging responses to facial expressions of emotion collected before subjects began treatment were compared with changes in anxiety following 8 weeks of venlafaxine administration . In addition , the magnitude of fMRI responses of subjects with GAD were compared with that of 15 control subjects ( 12 female subjects ) who did not have GAD and did not receive venlafaxine treatment . RESULTS The magnitude of treatment response was predicted by greater pretreatment reactivity to fearful faces in rACC and lesser reactivity in the amygdala . These individual differences in pretreatment rACC and amygdala reactivity within the GAD group were observed despite the fact that 1 ) the overall magnitude of pretreatment rACC and amygdala reactivity did not differ between subjects with GAD and control subjects and 2 ) there was no main effect of treatment on rACC-amygdala reactivity in the GAD group . CONCLUSIONS These findings show that this pattern of rACC-amygdala responsivity could prove useful as a predictor of venlafaxine treatment response in patients with GAD Although the role of emotion in socioeconomic decision making is increasingly recognised , the impact of specific emotional disorders , such as anxiety disorders , on these decisions has been surprisingly neglected . Twenty anxious patients and twenty matched controls completed a commonly used socioeconomic task ( the Ultimatum Game ) , in which they had to accept or reject monetary offers from other players . Anxious patients accepted significantly more unfair offers than controls . We discuss the implication s of these findings in light of recent models of anxiety , in particular the importance of interpersonal factors and assertiveness in an integrated model of decision making . Finally , we were able to show that pharmacological serotonin used to treat anxious symptomatology tended to normalise decision making , further confirming and extending the role of serotonin in co-operation , prosocial behaviour , and social decision making . These results show , for the first time , a different pattern of socioeconomic behaviour in anxiety disordered patients , in addition to the known memory , attentional and emotional biases that are part of this pathological condition More than half of anxiety and depression patients treated with an adequate course of antidepressants fail to fully improve . We retrospectively examined whether treatment-resistant depression and anxiety disorder patients responded to and tolerated augmentation with the atypical antipsychotic , aripiprazole . We report on patients with depression and anxiety disorders , including panic disorder , generalized anxiety disorder , social anxiety and post-traumatic stress disorder , who had an incomplete response to a variety of selective serotonin reuptake inhibitors ( SSRIs ) and who received augmentation with aripiprazole . The primary outcome measure was the Clinical Global Impression of Improvement ( CGI-I ) . In the intent-to-treat analysis , the mean±SD CGI-S was 3.8±1.3 at endpoint . Fifty-nine percent of subjects received CGI-I ratings of 1 or 2 , ‘ much improved ’ or ‘ very much improved , ’ in terms of their depression and anxiety symptoms at the end of 12 weeks . Several patients showed an early ( weeks 1–5 ) , as well as sustained , response to augmentation with doses of aripiprazole between 15 and 30 mg/day . The results suggest that aripiprazole may be effective as an augmentation for patients with persistent depressive and anxiety disorders despite initial SSRI treatment . Because this is a retrospective case review , further prospect i ve studies are required to confirm these findings This study investigated the temporal pattern of brain response to emotional stimuli during 28 days of alprazolam treatment among patients with generalized anxiety disorder ( GAD ) r and omized 2:1 to drug or placebo in a double-blind design . Functional magnetic resonance imaging scans obtained during an emotion face matching task ( EFMT ) and an affective stimulus expectancy task ( STIMEX ) were performed at baseline , one hour after initial drug administration and 28 days later . Alprazolam significantly reduced scores on the Hamilton Anxiety Scale and the Penn State Worry Question naire after one week and 28 days of treatment . Brain activation in the amygdala during the EFMT and in the insula during the STIMEX was reduced one hour after alprazolam administration but returned to baseline levels at Day 28 . Exploratory analyses revealed significant treatment differences in brain activity during the STIMEX on Day 28 in frontal lobe , cau date nucleus , middle temporal gyrus , secondary visual cortex , and supramarginal gyrus . These results are consistent with the notion that the neural mechanisms supporting sustained treatment effects of benzodiazepines in GAD differ from those underlying their acute effects Some research ers have recently suggested that antidepressants may be superior to benzodiazepines in the alleviation of generalized anxiety . In a 6-week , double-blind , parallel- design study with flexible dosage scheduling , the authors compared the effects of alprazolam with those of imipramine in 60 patients who had generalized anxiety disorder . On rating scales that contained both psychic and somatic symptoms , patients in both treatment groups improved to a similar degree after 2 weeks . However , alprazolam was more effective in attenuating somatic symptoms , and imipramine was more effective in attenuating psychic symptoms such as dysphoria and negative anticipatory thinking . The authors ' results suggest that , in generalized anxiety , somatic symptoms and hyperarousal selectively respond to drugs acting on the gamma Output:	RESULTS The available studies have shown impairments in ventrolateral and dorsolateral prefrontal cortex , anterior cingulate , posterior parietal regions , and amygdala in both pediatric and adult GAD patients , mostly in the right hemisphere .
MS22153	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE The purpose of the study was to investigate the effect of comorbid depression on glycemic control and on response to a telemedicine case management intervention for elderly , ethnically diverse diabetic patients . RESEARCH DESIGN AND METHODS Medicare beneficiaries in underserved areas were participants ( n = 1,665 ) in the Informatics for Diabetes Education and Telemedicine ( IDEATel ) project and r and omized to a telemedicine case management intervention or usual care . The data analyzed include baseline demographics ( age , sex , race/ethnicity , marital status , insulin use , years of education , years of diabetes , and pack-years smoked ) and measures of glycemic control ( HbA(1c ) [ A1C ] ) , comorbidity , diabetes symptom severity , functional disability and depression , and 1-year ( n = 1,578 ) A1C . The association between depression and glycemic control was analyzed cross-sectionally and prospect ively . RESULTS At baseline , there was a significant correlation between depression and A1C and a trend for depression to predict A1C when other factors were controlled . However , in prospect i ve analyses , depression did not predict change in A1C , either in the control or intervention group . CONCLUSIONS In this large sample of elderly diabetic patients , a weak relationship between depression and A1C was found , but depression did not prospect ively predict change in glycemic control . Thus , there is no evidence that depression should be used to exclude patients from interventions . Also , we should evaluate the impact of depression on outcomes other than glycemic control Purpose The purpose of this study was to examine whether integrating depression treatment into care for type 2 diabetes mellitus among older African Americans improved medication adherence , glycemic control , and depression outcomes . Methods Older African Americans prescribed pharmacotherapy for type 2 diabetes mellitus and depression from physicians at a large primary care practice in west Philadelphia were r and omly assigned to an integrated care intervention or usual care . Adherence was assessed at baseline , 2 , 4 , and 6 weeks using the Medication Event Monitoring System to assess adherence . Outcomes assessed at baseline and 12 weeks included st and ard laboratory tests to measure glycemic control and the Center for Epidemiologic Studies Depression Scale ( CES-D ) to assess depression . Results In all , 58 participants aged 50 to 80 years participated . The proportion of participants who had 80 % or greater adherence to an oral hypoglycemic ( intervention 62.1 % vs usual care 24.1 % ) and an antidepressant ( intervention 62.1 % vs usual care 10.3 % ) was greater in the intervention group in comparison with the usual care group at 6 weeks . Participants in the integrated care intervention had lower levels of glycosylated hemoglobin ( intervention 6.7 % vs usual care 7.9 % ) and fewer depressive symptoms ( CES-D mean scores : intervention 9.6 vs usual care 16.6 ) compared with participants in the usual care group at 12 weeks . Conclusion A pilot r and omized controlled trial integrating type 2 diabetes mellitus treatment and depression was successful in improving outcomes among older African Americans . Integrated interventions may be more feasible and effective in real-world practice s with competing dem and s for limited re sources BACKGROUND Patients with depression and poorly controlled diabetes , coronary heart disease , or both have an increased risk of adverse outcomes and high health care costs . We conducted a study to determine whether coordinated care management of multiple conditions improves disease control in these patients . METHODS We conducted a single-blind , r and omized , controlled trial in 14 primary care clinics in an integrated health care system in Washington State , involving 214 participants with poorly controlled diabetes , coronary heart disease , or both and coexisting depression . Patients were r and omly assigned to the usual-care group or to the intervention group , in which a medically supervised nurse , working with each patient 's primary care physician , provided guideline -based , collaborative care management , with the goal of controlling risk factors associated with multiple diseases . The primary outcome was based on simultaneous modeling of glycated hemoglobin , low-density lipoprotein ( LDL ) cholesterol , and systolic blood-pressure levels and Symptom Checklist-20 ( SCL-20 ) depression outcomes at 12 months ; this modeling allowed estimation of a single overall treatment effect . RESULTS As compared with controls , patients in the intervention group had greater overall 12-month improvement across glycated hemoglobin levels ( difference , 0.58 % ) , LDL cholesterol levels ( difference , 6.9 mg per deciliter [ 0.2 mmol per liter ] ) , systolic blood pressure ( difference , 5.1 mm Hg ) , and SCL-20 depression scores ( difference , 0.40 points ) ( P<0.001 ) . Patients in the intervention group also were more likely to have one or more adjustments of insulin ( P=0.006 ) , antihypertensive medications ( P<0.001 ) , and antidepressant medications ( P<0.001 ) , and they had better quality of life ( P<0.001 ) and greater satisfaction with care for diabetes , coronary heart disease , or both ( P<0.001 ) and with care for depression ( P<0.001 ) . CONCLUSIONS As compared with usual care , an intervention involving nurses who provided guideline -based , patient-centered management of depression and chronic disease significantly improved control of medical disease and depression . ( Funded by the National Institute of Mental Health ; Clinical Trials.gov number , NCT00468676 . ) Objectives To determine the effectiveness of collaborative care in reducing depression in primary care patients with diabetes or heart disease using practice nurses as case managers . Design A two-arm open r and omised cluster trial with wait-list control for 6 months . The intervention was followed over 12 months . Setting Eleven Australian general practice s , five r and omly allocated to the intervention and six to the control . Participants 400 primary care patients ( 206 intervention , 194 control ) with depression and type 2 diabetes , coronary heart disease or both . Intervention The practice nurse acted as a case manager identifying depression , review ing pathology results , lifestyle risk factors and patient goals and priorities . Usual care continued in the controls . Main outcome measure A five-point reduction in depression scores for patients with moderate-to-severe depression . Secondary outcome was improvements in physiological measures . Results Mean depression scores after 6 months of intervention for patients with moderate-to-severe depression decreased by 5.7±1.3 compared with 4.3±1.2 in control , a significant ( p=0.012 ) difference . ( The plus – minus is the 95 % confidence range . ) Intervention practice s demonstrated adherence to treatment guidelines and intensification of treatment for depression , where exercise increased by 19 % , referrals to exercise programmes by 16 % , referrals to mental health workers ( MHWs ) by 7 % and visits to MHWs by 17 % . Control- practice exercise did not change , whereas referrals to exercise programmes dropped by 5 % and visits to MHWs by 3 % . Only referrals to MHW increased by 12 % . Intervention improvements were sustained over 12 months , with a significant ( p=0.015 ) decrease in 10-year cardiovascular disease risk from 27.4±3.4 % to 24.8±3.8 % . A review of patients indicated that the study 's safety protocol s were followed . Conclusions TrueBlue participants showed significantly improved depression and treatment intensification , sustained over 12 months of intervention and reduced 10-year cardiovascular disease risk . Collaborative care using practice nurses appears to be an effective primary care intervention . Trial registration ACTRN12609000333213 ( Australia and New Zeal and Clinical Trials Registry ) OBJECTIVE To determine whether evidence -based socioculturally adapted collaborative depression care improves receipt of depression care and depression and diabetes outcomes in low-income Hispanic subjects . RESEARCH DESIGN AND METHODS This was a r and omized controlled trial of 387 diabetic patients ( 96.5 % Hispanic ) with clinical ly significant depression recruited from two public safety-net clinics from August 2005 to July 2007 and followed over 18 months . Intervention ( INT group ) included problem-solving therapy and /or antidepressant medication based on a stepped-care algorithm ; first-line treatment choice ; telephone treatment response , adherence , and relapse prevention follow-up over 12 months ; plus systems navigation assistance . Enhanced usual care ( EUC group ) included st and ard clinic care plus patient receipt of depression educational pamphlets and a community re source list . RESULTS INT patients had significantly greater depression improvement ( ≥50 % reduction in Symptom Checklist-20 depression score from baseline ; 57 , 62 , and 62 % vs. the EUC group 's 36 , 42 , and 44 % at 6 , 12 , and 18 months , respectively ; odds ratio 2.46–2.57 ; P < 0.001 ) . Mixed-effects linear regression models showed a significant study group – by – time interaction over 18 months in diabetes symptoms ; anxiety ; Medical Outcomes Study Short-Form Health Survey ( SF-12 ) emotional , physical , and pain-related functioning ; Sheehan disability ; financial situation ; and number of social stressors ( P = 0.04 for disability and SF-12 physical functioning , P < 0.001 for all others ) but no study group – by – time interaction in A1C , diabetes complications , self-care management , or BMI . CONCLUSIONS Socioculturally adapted collaborative depression care improved depression , functional outcomes , and receipt of depression treatment in predominantly Hispanic patients in safety-net clinics PURPOSE Medication nonadherence , inconsistent patient self-monitoring , and inadequate treatment adjustment exacerbate poor disease control . In a collaborative , team-based , care management program for complex patients ( TEAMcare ) , we assessed patient and physician behaviors ( medication adherence , self-monitoring , and treatment adjustment ) in achieving better outcomes for diabetes , coronary heart disease , and depression . METHODS A r and omized controlled trial was conducted ( 2007–2009 ) in 14 primary care clinics among 214 patients with poorly controlled diabetes ( glycated hemoglobin [ HbA1c ] ≥8.5 % ) or coronary heart disease ( blood pressure > 140/90 mm Hg or low-density lipoprotein cholesterol > 130 mg/dL ) with coexisting depression ( Patient Health Question naire-9 score ≥10 ) . In the TEAMcare program , a nurse care manager collaborated closely with primary care physicians , patients , and consultants to deliver a treat-to-target approach across multiple conditions . Measures included medication initiation , adjustment , adherence , and disease self-monitoring . RESULTS Pharmacotherapy initiation and adjustment rates were sixfold higher for antidepressants ( relative rate [ RR ] = 6.20 ; P < .001 ) , threefold higher for insulin ( RR = 2.97 ; P < .001 ) , and nearly twofold higher for antihypertensive medications ( RR = 1.86 , P < .001 ) among TEAMcare relative to usual care patients . Medication adherence did not differ between the 2 groups in any of the 5 therapeutic classes examined at 12 months . TEAMcare patients monitored blood pressure ( RR = 3.20 ; P < .001 ) and glucose more frequently ( RR = 1.28 ; P = .006 ) . CONCLUSIONS Frequent and timely treatment adjustment by primary care physicians , along with increased patient self-monitoring , improved control of diabetes , depression , and heart disease , with no change in medication adherence rates . High baseline adherence rates may have exerted a ceiling effect on potential improvements in medication adherence Abstract Objective : To test whether a structured self-monitoring of blood glucose ( SMBG ) protocol reduces depressive symptoms and diabetes distress . Research design and methods : A 12-month , cluster-r and omised , clinical trial compared patients who received a collaborative , structured SMBG , physician/patient intervention with an active control . Studied were 483 insulin naïve type 2 diabetes patients ( experimental = 256 , control = 227 ) ( ≥ 7.5 % HbA1c ) from 34 primary care practice s ( experimental = 21 , control = 13 ) . Experimental patients used a paper tool to record a 7-point SMBG profile on each of three consecutive days prior to their quarterly physician visit . Patients and physicians interpreted SMBG results to make medication and lifestyle changes . Clinical trial registration : NIH Trial Registry Number : NCT00674986 . Main outcome measures : Depressive symptoms ( Patient Health Question naire : PHQ-8 ) , diabetes-related distress ( Diabetes Distress Scale : DDS ) . HbA1c and SMBG frequency were assessed quarterly ; data were analysed using Linear Mixed Models ( LMM ) for intent-to-treat ( ITT ) and per protocol ( PP ) analyses . Results : ITT analyses showed significant improvement in depression and disease-related distress among experimental and control patients from baseline Output:	Depression remission did not predict better glycaemic control across studies . Limited evidence from short-to-medium term RCTs predominantly conducted in the USA suggests that collaborative care for depression significantly improves both depression and glycaemia outcomes , independently , in people with comorbid depression and diabetes
MS22154	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Hepatitis C is the most common indication for liver transplantation ( LT ) in the United States . Recurrence of hepatitis C virus ( HCV ) infection post-LT remains a problem for which there is no completely satisfactory treatment . The aim of the present study is to evaluate mycophenolate mofetil ( MMF ) , which has both immunosuppressive and antiviral properties , to determine whether it is associated with a difference in the rate of HCV recurrence and also examine its impact on patient and graft survival . Between August 1995 and May 1998 , a total of 106 patients who were HCV positive before LT were r and omized to tacrolimus ( TAC ) and prednisone versus TAC , prednisone , and MMF therapy . The rate of recurrence of HCV , patient and graft survival , incidences of rejection , and histological findings were examined . Fifty six patients were r and omized to TAC and steroid therapy ( double [ D ] drug ; group D ) , and 50 patients were r and omized to TAC , steroid , and MMF therapy ( triple [ T ] drug ; group T ) . Liver biopsies were performed when liver function was abnormal ; protocol liver biopsies were not performed . Mean follow-up was 4.3 + /- 0.8 years . Actuarial patient survivals at 4 years were 72.6 % in group D and 73.8 % in group T ( P = not significant ) . Actuarial graft survivals at 4 years were 65.6 % in group D and 65.4 % in group T. One patient in group D and 2 patients in group T underwent a second LT for recurrent HCV . One patient in each group died of recurrent HCV without re-LT . Twenty-six patients in group D ( 46.4 % ) and 23 patients in group T ( 46.0 % ) showed signs of recurrent HCV . Mean hepatitis activity index ( HAI ) scores were 7.4 + /- 2.7 in group D and 7.0 + /- 3.4 in group T , and mean fibrosis scores were 2.9 + /- 1.7 in group D and 2.6 + /- 1.1 in group T. The rate of rejection was 0.57/patient in each group for the entire follow-up period . None of these values reached statistical significance . Rates of HCV recurrence , graft loss or death from recurrent HCV , and 4-year actuarial patient and graft survival were not different between the groups . In liver transplant recipients with HCV , MMF has no impact on patient survival , graft survival , rejection , or rate of HCV recurrence based on biochemical changes and histological findings . In addition , there was no difference in HAI or fibrosis score between the two groups . Either MMF has no anti-HCV effect or its immunosuppressive properties overwhelm its antiviral effect in the clinical setting Background . In this article , we explore the virological response to two types of interferon based treatment in recurrent hepatitis C virus in liver recipients who received thymoglobulin induction . Methods . Fifty consecutive patients were r and omized to receive PEG interferon alpha 2b ( 1.0 & mgr;g/kg per week ) , ribavirin ( 800 mg/d ) plus amantadine ( 200 mg/d ) , or PEG interferon alpha 2b ( 1.0 & mgr;g/kg per week ) plus ribavirin ( 800 mg/d ) . The primary endpoint was absence of hepatitis C virus RNA 6 months posttreatment . The secondary endpoint was change in fibrosis at 1 year . Results . Only 30 patients completed 1 year of treatment . In an intention to treat analysis , the sustained virological response ( SVR ) rate was 26 % in I/R/A group and 50 % in I/R group . By per protocol , the overall SVR rate was 57 % . Fibrosis progression by at least one stage was noted in 37 % patients . Twenty-nine percent of patients who achieved SVR had shown fibrosis progression by at least one stage whereas 46 % nonresponders showed fibrosis progression ( P = NS ) . Conclusion . This is the first study exploring the efficacy of pegylated interferon-based antiviral treatment in patients who received a steroid-free protocol . Our data is encouraging and shows that if liver transplant recipients can tolerate treatment for 1 year there is a reasonable chance of SVR OBJECTIVES To analyze sources search ed in Cochrane review s , to determine the proportion of trials included in review s that are indexed in major data bases , and to compare the quality of these trials with those from other sources . METHODS All new systematic review s in the Cochrane Library , Issue1 2001 , that were restricted to r and omized controlled trials ( RCTs ) or quasi- RCTs were selected . The sources search ed in the review s were recorded , and the trials included were checked to see whether they were indexed in four major data bases . Trials not indexed were checked to determine how they could be identified . The quality of trials found in major data bases was compared with those found from other sources . RESULTS The range in the number of data bases search ed per review ranged between one and twenty-seven . The proportion of the trials in the four data bases were Cochrane Controlled Trials Register = 78.5 % , MEDLINE = 68.8 % , Embase = 65.0 % , and Science/Social Sciences Citation Index = 60.7 % . Search ing another twenty-six data bases after Cochrane Controlled Trials Register ( CCTR ) , MEDLINE , and Embase only found 2.4 % additional trials . There was no significant difference between trials found in the CCTR , MEDLINE , and Embase compared with other trials , with respect to adequate allocation concealment or sample size . CONCLUSIONS There was a large variation between review s in the exhaustiveness of the literature search es . CCTR was the single best source of RCTs . Additional data base search ing retrieved only a small percentage of extra trials . Contacting authors and manufacturers to find unpublished trials appeared to be a more effective method of obtaining the additional better quality trials The aim of the study was to observe the frequency of neutropenia during Pegylated Interferon/Ribavirin therapy in patient with chronic hepatitis C ; to compare the efficacy of two strategies of management of neutropenia -- with Interferon dose modification and with Neupogen administration ; to compare the effectiveness rate of sustained viral response ( SVR ) in patients with Pegylated Interferon dose modification and in patients treated by using granulocyte colony-stimulating factor G-CSF-filgrastim . ( Neupogen ) . Study enrolled 47 patients with chronic active hepatitis C , aged 23 - 64 . ( 38 male and 9 female ) . All patients had HCV genotype 1b . Significant neurtopenia ( ANC<750 mm3 ) and severe neurtopenia ( ANC<500 mm3 ) developed in 41 of 47 patients ( 87 % ) . 41 patients with neurtopenia were r and omized into two groups . The first group--22 patients who received granulocyte colony-stimulating factor ( G-CSF , or filgrastim ) 300 mcg s/c weekly for correction of neutropenia and the second group--19 patients treated either with Interferon dose reduction or temporarily inhibit of Interferon treatment . In all 22 patients of the first group neutropenia was normalized without reduction and /or inhibit of Pegylated interferon . Neupogen was well tolerated and in all 22 patients the improvement of quality of life ( QOL ) was observed . It was concluded that dose reduction or temporary inhibit of Pegylated Interferon in the second group negatively acts on antiviral treatment response in patients with HCV genotype 1 . In patients with PEG-IFN/RBV therapy Neupogen effectively manages neutropenia and gives opportunity to maintain interferon dose ( without reduction ) . Neupogen has the potential to improve adherence rates , which may in turn improve SVR Ischemic preconditioning ( IPC ) has the potential to decrease graft injury and morbidity after liver transplantation . We prospect ively investigated the safety and efficacy of 5 minutes of IPC induced by hilar clamping in local deceased donor livers r and omized 1:1 to st and ard ( STD ) recovery ( N = 28 ) or IPC ( N = 34 ) . Safety was assessed by measurement of heart rate , blood pressure , and visual inspection of abdominal organs during recovery , and efficacy by recipient aminotransferases ( aspartate aminotransferase [ AST ] and alanine aminotransferase [ ALT ] , both measured in U/L ) , total bilirubin , and international normalized ratio of prothrombin time ( INR ) after transplantation . IPC performed soon after laparotomy did not cause hemodynamic instability or visceral congestion . Recipient median AST , median ALT , and mean INR , in STD vs. IPC were as follows : day 1 AST 696 vs. 841 U/L ; day 3 AST 183 vs. 183 U/L ; day 1 ALT 444 vs. 764 U/L ; day 3 ALT 421 vs. 463 U/L ; day 1 INR 1.7 + /- .4 vs. 2.0 + /- .8 ; and day 3 INR 1.3 + /- .2 vs. 1.4 + /- .3 ; all P > .05 . No instances of nonfunction occurred . The 6-month graft and patient survival STD vs. IPC were 82 vs. 91 % and median hospital stay was 10 vs. 8 days ; both P > .05 . In conclusion , deceased donor livers tolerated 5 minutes of hilar clamping well , but IPC did not decrease graft injury . Further trials with longer periods of preconditioning such as 10 minutes are needed BACKGROUND & AIMS Recurrence of hepatitis C virus ( HCV ) infection is a relevant problem of liver transplantation programs . We evaluated the effect of antiviral therapy on disease progression in 81 HCV-infected liver transplantation recipients . METHODS Patients with mild hepatitis C recurrence ( fibrosis stage F0 to F2 , n = 54 ) were r and omized to no treatment ( group A , n = 27 ) or peginterferon alfa-2b/ribavirin for 48 weeks ( group B , n = 27 ) . Patients with severe recurrence ( F3 to F4 , cholestatic hepatitis ) were treated ( group C , n = 27 ) . All patients ( n = 81 ) underwent a liver biopsy at baseline and after follow-up ; paired hepatic venous pressure gradient ( HVPG ) measurements were available in 51 patients . RESULTS Thirteen ( 48 % ) patients of group B and 5 ( 18.5 % ) of group C achieved sustained virological response . Liver fibrosis progressed > or = 1 stage in 40 ( 49 % ) of 81 patients : 19 ( 70 % ) of group A versus 7 ( 26 % ) of group B ( P = .001 ) and in 14 ( 54 % ) of group C. HVPG increased ( 6.5 to 13 mm Hg , P < .01 ) in patients in whom fibrosis worsened , whereas it decreased ( 5 to 3.5 mm Hg , P = .017 ) or remained unchanged in those with fibrosis improvement or stabilization , respectively . The only variable independently associated with fibrosis improvement/stabilization was treatment ( odds ratio [ OR ] = 3.7 , 95 % confidence interval [ CI ] 1.3 to 10 , P = .009 ) . Among treated patients , alanine aminotransferase ( ALT ) normalization and viral clearance were independently associated with histological or hemodynamic improvement/stabilization ( OR 5.3 , 95 % CI 1.5 to 18 , P < .01 ; OR 7.4 , 95 % CI 1.4 to 38 , P = .01 ; respectively ) . CONCLUSIONS Our data demonstrate that in liver transplantation recipients , antiviral therapy slows disease progression ( particularly in sustained virological responders ) , as shown by its effects on liver histology and on HVPG Allograft reinfection with hepatitis C virus ( HCV ) in transplant recipients occurs commonly and represents a major concern in the transplant setting . Suppression of viral replication in HCV transplant patients should prevent or delay progression to cirrhosis and graft failure . In this ongoing study , we present preliminary data from a prospect i ve trial of st and ard interferon ( IFN ) alpha-2b ( 2 million units daily ) for 3 months and subsequent peginterferon ( PEG IFN ) alpha-2b ( 1.5 microg/kg/week ) for 9 months . IFN therapy was combined with ribavirin ( 10 to 12 mg/kg ) . So far , HCV has become undetectable by qualitative PCR in 33 % of patients while 25 % had a reduction of HCV RNA to undetectable by the bDNA assay and 42 % had no virological response after 6 months of therapy . A biochemical response was detected in 42 % of patients . Improvement of inflammatory activity was observed in 42 % of patients after 6 months . In three patients anemia necessitated administration of erythropoietin and three patients received granulocyte-colony stimulating factor ( G-CSF ) due to leucopenia [ corrected ] In conclusion , we observed that daily IFN alpha-2b and subsequent PEG IFN alpha-2b therapy in combination with ribavir Output:	There was no significant difference in the mortality , graft rejection , or in re-transplantation between intervention and control in any of the comparisons that reported these outcomes . None of the trials reported liver decompensation or quality of life . Life-threatening adverse effects were not reported in either group in any of the comparisons . Considering the lack of clinical benefit and the frequent adverse effects , there is currently no evidence to recommend antiviral treatment for recurrent liver graft infection with HCV .
MS22155	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objectives To estimate survival after a diagnosis of dementia in primary care , compared with people without dementia , and to determine incidence of dementia . Design Cohort study using data from The Health Improvement Network ( THIN ) , a primary care data base . Setting 353 general practice s in the United Kingdom providing data to THIN . Participants All adults aged 60 years or over with a first ever code for dementia from 1990 to 2007 ( n=22 529 ) ; r and om sample of five participants without dementia for every participant with dementia matched on practice and time period ( n=112 645 ) . Main outcome measures Median survival by age and sex ; mortality rates ; incidence of dementia by age , sex , and deprivation . Results The median survival of people with dementia diagnosed at age 60 - 69 was 6.7 ( interquartile range 3.1 - 10.8 ) years , falling to 1.9 ( 0.7 - 3.6 ) years for those diagnosed at age 90 or over . Adjusted mortality rates were highest in the first year after diagnosis ( relative risk 3.68 , 95 % confidence interval 3.44 to 3.94 ) . This dropped to 2.49 ( 2.29 to 2.71 ) in the second year . The incidence of recorded dementia remained stable over time ( 3 - 4/1000 person years at risk ) . The incidence was higher in women and in younger age groups ( 60 - 79 years ) living in deprived areas . Conclusions Median survival was much lower than in screened population s. These clinical ly relevant estimates can assist patients and carers , clinicians , and policy makers when planning support for this population . The high risk of death in the first year after diagnosis may reflect diagnoses made at times of crisis or late in the disease trajectory . Late recording of diagnoses of dementia in primary care may result in missed opportunities for potential early interventions This pilot aims to better underst and the market for childcare in Saudi Arabia – both the supply and dem and sides – and to design a r and omized controlled experiment to test whether access to affordable day care ( in the form of subsidies , for example ) would incentivize Saudi mothers to search actively for employment and to remain employed once they are hired . In addition , the study seeks to underst and the degree to which employment early on in one ’s life impacts employment in later stages . The pilot will provide information on the groups of women the experiment should target , appropriate levels for the childcare subsidy , and the quality and current geographic locations of daycare sites . Expected Impact Determine the effects of facilitating childcare access on Saudi women ’s employment . PRINCIPAL INVESTIGATORS  Boston University Patricia Cortes  Harvard University Claudia Goldin  Swarthmore College Jennifer Background Globally , dengue infections constitute a significant public health burden . In recent decades , Malaysia has become a dengue hyper-endemic country with the co-circulation of the four dengue virus serotypes . The cyclical dominance of sub-types contributes to a pattern of major outbreaks . The consequences can be observed in the rising incidence of reported dengue cases and dengue related deaths . Underst and ing the complex interaction of the dengue virus , its human hosts and the mosquito vectors at the community level may help develop strategies for addressing the problem . Methods A prospect i ve cohort study will be conducted in Segamat district of Johor State in Peninsular Malaysia . Research ers received approval from the Malaysian Medical Research Ethics Committee and Monash University Human Research Ethics Committee . The study will be conducted at a Malaysian based health and demographic surveillance site over a 1 year period in three different setting s ( urban , semi-urban and rural ) . The study will recruit healthy adults ( male and female ) aged 18 years and over , from three ethnic groups ( Malay , Chinese and Indian ) . The sample size calculated using the Fleiss method with continuity correction is 333 . Sero-surveillance of participants will be undertaken to identify asymptomatic , otherwise healthy cases ; cases with dengue fever who are managed as out- patients ; and cases with dengue fever admitted to a hospital . A genetic analysis of the participants will be undertaken to determine whether there is a relationship between genetic predisposition and disease severity . A detailed medical history , past history of dengue infection , vaccination history against other flaviviruses such as Japanese encephalitis and Yellow fever , and the family history of dengue infection will also be collected . In addition , a mosquito surveillance will be carried out simultaneously in recruitment areas to determine the molecular taxonomy of circulating vectors . Discussion The research findings will estimate the burden of asymptomatic and symptomatic dengue at the community level . It will also examine the relationship between virus serotypes and host genotypes , and the association of the clinical manifestation of the early phase with the entire course of illness BACKGROUND Although statins reduce coronary and cerebrovascular morbidity and mortality in middle-aged individuals , their efficacy and safety in elderly people is not fully established . Our aim was to test the benefits of pravastatin treatment in an elderly cohort of men and women with , or at high risk of developing , cardiovascular disease and stroke . METHODS We did a r and omised controlled trial in which we assigned 5804 men ( n=2804 ) and women ( n=3000 ) aged 70 - 82 years with a history of , or risk factors for , vascular disease to pravastatin ( 40 mg per day ; n=2891 ) or placebo ( n=2913 ) . Baseline cholesterol concentrations ranged from 4.0 mmol/L to 9.0 mmol/L. Follow-up was 3.2 years on average and our primary endpoint was a composite of coronary death , non-fatal myocardial infa rct ion , and fatal or non-fatal stroke . Analysis was by intention-to-treat . FINDINGS Pravastatin lowered LDL cholesterol concentrations by 34 % and reduced the incidence of the primary endpoint to 408 events compared with 473 on placebo ( hazard ratio 0.85 , 95 % CI 0.74 - 0.97 , p=0.014 ) . Coronary heart disease death and non-fatal myocardial infa rct ion risk was also reduced ( 0.81 , 0.69 - 0.94 , p=0.006 ) . Stroke risk was unaffected ( 1.03 , 0.81 - 1.31 , p=0.8 ) , but the hazard ratio for transient ischaemic attack was 0.75 ( 0.55 - 1.00 , p=0.051 ) . New cancer diagnoses were more frequent on pravastatin than on placebo ( 1.25 , 1.04 - 1.51 , p=0.020 ) . However , incorporation of this finding in a meta- analysis of all pravastatin and all statin trials showed no overall increase in risk . Mortality from coronary disease fell by 24 % ( p=0.043 ) in the pravastatin group . Pravastatin had no significant effect on cognitive function or disability . INTERPRETATION Pravastatin given for 3 years reduced the risk of coronary disease in elderly individuals . PROSPER therefore extends to elderly individuals the treatment strategy currently used in middle aged people Sleep disturbances and decrements of daytime performance have been attributed to HMG-CoA reductase inhibitors . As a rule , lipophilic compounds more readily cross the blood-brain barrier and are more likely to affect central nervous system function . The authors compared the effects of lovastatin ( 40 mg ) , a lipophilic compound , to pravastatin ( 40 mg ) , a hydrophilic compound , in a 6-week , double-blind , r and omized , placebo-controlled , three-way Latin square design , cross-over study on 22 men with hypercholesterolemia . Patients had LDL cholesterol of more than 165 mg/dL and triglyceride of less than 350 mg/dL after 6 weeks of a low-fat ( < 30 % ) , low-cholesterol ( < 300 mg/day ) diet . Compared with placebo , there were no significant effects of lovastatin or pravastatin on the following subjective and polysomnographic sleep measures : changes in total sleep time , time in each sleep stage , sleep efficiency , sleep latency , REM density , REM activity , and number of arousals . Similarly , there were no effects of the two drugs on measures of cognitive performance . A significant increase in the duration of nocturnal tumescence ( NPT ) was observed after 2 weeks of treatment with both study drugs . This effect was not significant after 6 weeks of treatment . Both lovastatin and pravastatin caused significant ( P < .05 compared with placebo ) decreases in total cholesterol ( by 20.9 and 20.6 % , respectively ) , LDL cholesterol ( by 27.8 and 29.9 % ) , and triglycerides ( by 13.6 and 3.7 % ) . Subjects ' HDL increased by 2.3 % with lovastatin ( NS ) and by 3.1 % with pravastatin ( P < .05 ) . Lipoprotein(a ) increased by 20.5 % with lovastatin and by 1.1 % with pravastatin ; these changes were not significantly different from placebo . ( ABSTRACT TRUNCATED AT 250 WORDS The aim of this prospect i ve cohort study was to evaluate the effects of lipid lowering agent ( LLA ) intake on cognitive function in 6,830 community-dwelling elderly persons . Cognitive performance ( global cognitive functioning , visual memory , verbal fluency , psychomotor speed , and executive function ) , clinical diagnosis of dementia , and fibrate and statin use , were evaluated at baseline , and 2 , 4 , and 7 year follow-up . Multivariate Cox models were stratified by gender and adjusted for sociodemographic characteristics , mental and physical health including vascular risk factors , and genetic vulnerability ( apolipoprotein E and cholesteryl ester transfer protein ) . For women but not men , fibrate use was specifically associated with an increased risk over 7 years of decline in visual memory only ( HR = 1.29 , 95 % CI = 1.09 - 1.54 , p = 0.004 ) , and did not increase risk for incident dementia . This association was independent of genetic vulnerability related to apolipoprotein E and cholesteryl exchange transfer protein polymorphisms and occurred only in women with higher low density lipoprotein (LDL)-cholesterol levels and treated with fibrate ( HR = 1.39 , 95 % CI = 1.08 - 1.79 , p = 0.01 ) and not in those with lower LDL-cholesterol levels irrespective of fibrate treatment . For both genders , no significant associations were found between statins ( irrespective of their lipophilicity ) and either cognitive decline or dementia incidence . This prospect i ve study , adjusting for multiple confounders , found no evidence that LLA given in late life reduced the risk of cognitive decline and dementia , but did raise the possibility that women with treatment-resistant high LDL-cholesterol may be at increased risk of decline in visual memory Because cerebrospinal fl(CSF ) abnormalities in presymptomatic subjects with PSEN1 ( presenilin 1 ) mutations may be observed 4 to 12 years prior to the estimated age at onset , it is possible to test putative therapies on the CSF analytes that correlate with neurodegeneration during this presymptomatic window of clinical opportunity . It is also possible to test the same therapy on a comparison group with increased risk status conferred by both hyperlipidemia and heterozygosity for apolipoprotein Ee4 . To our knowledge , the only putative therapy thus far tested in such a common design has been statin therapy . The results of these tests show increases in soluble amyloid precursor protein (sAPP)α correlating with statininduced decreases in serum cholesterol levels in the non-PSEN1 subjects . This result could be one functional correlate for part of the substantial risk reduction for late onset Alzheimer ’s disease recently reported in the Rotterdam study , a large , long-term prospect i ve statin trial . Statin therapy signifi cantly decreased both sAPPα and sAPPβ in presymptomatic PSEN1 subjects . Initially , elevated phospho-tau levels in PSEN1 subjects did not further increase during the 2 to 3 years of statin therapy , possibly indicative of a prophylactic eff ect . These results suggest that large and longer term trials of statin therapy correlating changes in CSF biomarker levels with clinical course may be warranted in both presymptomatic PSEN1 and non-PSEN1 subjects Background : Previously reported associations between statin use and incident dementia or cognitive decline have been inconsistent . We report the results from a 3-year prospect i ve study on the association of statin use on cognitive decline and incident dementia in elderly African Americans . Methods : A community-based cohort of 1,146 African Americans aged 70 and older living in Indianapolis , Indiana , was evaluated in 2001 and 2004 . The instrument used for cognitive assessment was the Community Screening Interview for Dementia ( CSI-D ) . Cognitive decline was defined as CSI-D scores measured at 2001 minus scores at 2004 . Measurements of low-density lipoprotein cholesterol ( LDL-C ) and C-reactive protein ( CRP ) were obtained from baseline blood sample s. Results : Adjusting for age at baseline , gender , education , and the possession of ApoE ε4 allele , baseline statin use was Output:	Although observational studies that considered statin use at or near the time of dementia diagnosis suggest a protective effect of statins , these findings could be attributable to reverse causation . RCTs and well-conducted observational studies of baseline statin use and subsequent cognition over several years of follow-up do not support a causal preventative effect of late-life statin use on cognitive decline or dementia .
MS22156	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Abstract The goal of this study was to develop a cognitive – behavioral self-help manual for anorexia nervosa . Patients diagnosed with anorexia nervosa ( N=102 ) , binge eating/purging type ( AN-B/P ) , were consecutively assigned to one of two conditions : 6-week manualized guided self-help or a wait-list control . All patients thereafter received inpatient treatment in a hospital for behavioral medicine . The primary outcome variable was the number of days in inpatient treatment . Secondary outcome variables were measures of psychopathology . Results showed that duration of inpatient treatment was significantly shorter ( by 5.2 days ) among participants receiving guided self-help . Body image , slimness ideal , general psychopathology , and some bulimic symptoms improved significantly during self-help . The authors conclude that , to increase effects of therapist-guided self-help in AN-B/P , additional variants of a self-help manual should be tried in different therapeutic setting The present study investigated the efficacy of self-help based on cognitive behaviour therapy in combination with Internet support in the treatment of bulimia nervosa and binge eating disorder . After confirming the diagnosis with an in-person interview , 73 patients were r and omly allocated to treatment or a waiting list control group . Treated individuals showed marked improvement after 12 weeks of self-help compared to the control group on both primary and secondary outcome measures . Intent-to-treat analyses revealed that 37 % ( 46 % among completers ) had no binge eating or purging at the end of the treatment and a considerable number of patients achieved clinical ly significant improvement on most of the other measures as well . The results were maintained at the 6-month follow-up , and provide evidence to support the continued use and development of self-help programmes OBJECTIVE The objective was to examine the effectiveness of a self-help treatment as a first line primary care intervention for binge eating disorder ( BED ) in obese patients . This study compared the effectiveness of a usual care plus self-help version of cognitive behavioral therapy ( shCBT ) to usual care ( UC ) only in ethnically/racially diverse obese patients with BED in primary care setting s in an urban center . METHOD 48 obese patients with BED were r and omly assigned to either shCBT ( N = 24 ) or UC ( N = 24 ) for four months . Independent assessment s were performed monthly throughout treatment and at post-treatment . RESULTS Binge-eating remission rates did not differ significantly between shCBT ( 25 % ) and UC ( 8.3 % ) at post-treatment . Mixed models of binge eating frequency determined using the Eating Disorder Examination ( EDE ) revealed significant decreases for both conditions but that shCBT and UC did not differ . Mixed models of binge eating frequency from repeated monthly EDE- question naire assessment s revealed a significant treatment-by-time interaction indicating that shCBT had significant reductions whereas UC did not during the four-month treatments . Mixed models revealed no differences between groups on associated eating disorder psychopathology or depression . No weight loss was observed in either condition . CONCLUSIONS Our findings suggest that pure self-help CBT did not show effectiveness relative to usual care for treating BED in obese patients in primary care . Thus , self-help CBT may not have utility as a front-line intervention for BED for obese patients in primary care and future studies should test guided-self-help methods for delivering CBT in primary care generalist setting OBJECTIVE A group dissonance-based eating disorder prevention program , in which young women critique the thin ideal , reduces eating disorder risk factors and symptoms , but it can be difficult to identify school clinicians with the time and expertise to deliver the intervention . Thus , we developed a prototype Internet version of this program and evaluated it in a preliminary trial . METHOD Female college students with body dissatisfaction ( N = 107 ; M age = 21.6 years , SD = 6.6 ) were r and omized to the Internet intervention , group intervention , educational video condition , or educational brochure condition . RESULTS Internet and group participants showed greater pre-post reductions in eating disorder risk factors and symptoms than video controls ( M ds = 0.47 and 0.54 , respectively ) and brochure controls ( M ds = 0.75 and 0.72 , respectively ) , with many effects reaching significance . Effects did not differ significantly for Internet versus group participants ( M ds = -0.13 ) or for video versus brochure controls ( M d = 0.25 ) . Effect sizes for the Internet intervention were similar to those previously observed for group versions of this intervention . CONCLUSIONS Results suggest that this prototype Internet intervention is as efficacious as the group intervention , implying that there would be merit in completing this intervention and evaluating it in a fully powered trial This study evaluated a targeted intervention design ed to alleviate body image and eating problems in adolescent girls that was delivered over the internet so as to increase access to the program . The program consisted of six , 90-minute weekly small group , synchronous on-line sessions and was facilitated by a therapist and manual . Participants were 73 girls ( mean age=14.4 years , SD=1.48 ) who self-identified as having body image or eating problems and were r and omly assigned to an intervention group ( n=36 ) ( assessed at baseline , post-intervention and at 2- and 6-months follow-up ) or a delayed treatment control group ( n=37 ) ( assessed at baseline and 6–7 weeks later ) . Clinical ly significant improvements in body dissatisfaction , disordered eating , and depression were observed at post-intervention and maintained at follow-up . Internet delivery was enthusiastically endorsed . The program offers a promising approach to improve body image and eating problems that also addresses geographic access problems The purpose of this study was to conduct an assessment of binge eating severity among obese persons . Two question naires were developed . A 16-item Binge Eating Scale was constructed describing both behavioral manifestations ( e.g. , eating large amounts of food ) and feeling/cognitions surrounding a binge episode ( e.g. , guilt , fear of being unable to stop eating ) . An 11-item Cognitive Factors Scale was developed measure two cognitive phenomena thought to be related to binge eating : the tendency to set unrealistic st and ards for a diet ( e.g. , eliminating " favorite foods " ) and low efficacy expectations for sustaining a diet . The results showed that the Binge Eating Scale successfully discriminated among persons judged by trained interviewers to have either no , moderate or severe binge eating problems . Significant correlation between the scales were obtained such that severe bingers tended to set up diets which were unrealistically strict while reporting low efficacy expectations to sustain a diet . The discussion highlighted the differences among obese persons on binge eating severity and emphasized the role of cognitions in the relapse of self control of eating OBJECTIVE This study examined the outcome of a body image and disordered eating intervention for midlife women . The intervention was specifically design ed to address risk factors that are pertinent in midlife . METHOD Participants were 61 women aged 30 to 60 years ( M = 43.92 , SD = 8.22 ) r and omly assigned to intervention ( n = 32 ) or ( delayed treatment ) control ( n = 29 ) groups . Following an 8-session facilitated group cognitive behavioral therapy-based intervention , outcomes from the Body Shape Question naire ; Eating Disorder Examination Question naire ; Body Image Avoidance Question naire ; Physical Appearance Comparison Scale ; Sociocultural Attitudes Towards Appearance Scale , Internalization subscale ; measures of appearance importance , cognitive re appraisal , and self-care ; Dutch Eating Behavior Question naire ; and Kessler Psychological Distress Scale were compared for statistical and clinical significance from baseline to posttest and 6-month follow-up . RESULTS Following the intent-to-treat principle , mixed-model analyses with a mixed within-between design demonstrated that the intervention group had large improvements that were statistically significantly different from the control group in body image , disordered eating , and risk factor variables and that were maintained at 6-month follow-up . Furthermore , the improvements were also of clinical importance . CONCLUSIONS This study provides support for the efficacy of an intervention to reduce body image and eating concerns in midlife women . Further research into interventions tailored for this population is warranted We performed a r and omized controlled study to test the relative efficacy of guided self-help ( gsh ) cognitive-behavioral therapy ( CBTgsh ) and behavioral weight loss treatment ( BWLgsh ) treatments for binge eating disorder ( BED ) . To provide an additional partial control for non-specific influences of attention , a third control ( CON ) treatment condition was included . We tested the treatments using a guided self-help approach given the promising results from initial studies using minimal therapist guidance . Ninety consecutive overweight patients ( 19 males , 71 females ) with BED were r and omly assigned ( 5:5:2 ratio ) to one of three treatments : CBTgsh ( N=37 ) , BWLgsh ( N=38 ) , or CON ( N=15 ) . The three 12-week treatment conditions were administered individually following guided self-help protocol s. Overall , 70 ( 78 % ) completed treatments ; CBTgsh ( 87 % ) and CON ( 87 % ) had significantly higher completion rates than BWLgsh ( 67 % ) . Intent-to-treat analyses revealed that CBTgsh had significantly higher remission rates ( 46 % ) than either BWLgsh ( 18 % ) or CON ( 13 % ) . Weight loss was minimal and differed little across treatments . The findings suggest that CBT , administered via guided self-help , demonstrates efficacy for BED , but not for obesity . The findings support CBT administered via guided self-help as a first step in the treatment of BED and provide evidence for its specific effects CONTEXT Eating disorders , an important health problem among college-age women , may be preventable , given that modifiable risk factors for eating disorders have been identified and interventions have been evaluated to reduce these risk factors . OBJECTIVE To determine if an Internet-based psychosocial intervention can prevent the onset of eating disorders ( EDs ) in young women at risk for developing EDs . SETTING San Diego and the San Francisco Bay Area in California . PARTICIPANTS College-age women with high weight and shape concerns were recruited via campus e-mails , posters , and mass media . Six hundred thirty-seven eligible participants were identified , of whom 157 were excluded , for a total sample of 480 . Recruitment occurred between November 13 , 2000 , and October 10 , 2003 . Intervention A r and omized controlled trial of an 8-week , Internet-based cognitive-behavioral intervention ( Student Bodies ) that included a moderated online discussion group . Participants were studied for up to 3 years . MAIN OUTCOME MEASURES The main outcome measure was time to onset of a sub clinical or clinical ED . Secondary measures included change in scores on the Weight Concerns Scale , Global Eating Disorder Examination Question naire , and Eating Disorder Inventory drive for thinness and bulimia subscales and depressed mood . Moderators of outcome were examined . RESULTS There was a significant reduction in Weight Concerns Scale scores in the Student Bodies intervention group compared with the control group at postintervention ( P < .001 ) , 1 year ( P < .001 ) , and 2 years ( P < .001 ) . The slope for reducing Weight Concerns Scale score was significantly greater in the treatment compared with the control group ( P = .02 ) . Over the course of follow-up , 43 participants developed sub clinical or clinical EDs . While there was no overall significant difference in onset of EDs between the intervention and control groups , the intervention significantly reduced the onset of EDs in 2 subgroups identified through moderator analyses : ( 1 ) participants with an elevated body mass index ( BMI ) ( > or = 25 , calculated as weight in kilograms divided by height in meters squared ) at baseline and ( 2 ) at 1 site , participants with baseline compensatory behaviors ( eg , self-induced vomiting , laxative use , diuretic use , diet pill use , driven exercise ) . No intervention participant with an elevated baseline BMI developed an ED , while the rates of onset of ED in the comparable BMI control group ( based on survival analysis ) were 4.7 % at 1 year and 11.9 % at 2 years . In the subgroup with a BMI of 25 or higher , the cumulative survival incidence was significantly lower at 2 years for the intervention compared with the control group ( 95 % confidence interval , 0 % for intervention group ; 2.7 % to 21.1 % for control group ) . For the San Francisco Bay Area site sample with baseline compensatory behaviors , 4 % of participants in the intervention group developed EDs at 1 year and 14.4 % , by 2 years . Rates for the comparable control group were 16 % and 30.4 % , respectively . CONCLUSIONS Among college-age women with high weight and shape concerns , an 8-week , Internet-based cognitive-behavioral intervention can significantly reduce weight and shape concerns for up to 2 years and decrease risk for the onset of EDs , at least in some high-risk groups . To our knowledge , this is the first study to show that EDs can be prevented in high-risk groups Previous research has addressed the issues of behavior change and eating disorder prevention among adolescents and young women . The current study was design ed to evaluate : ( a ) whether an 8-week psychoeducational intervention can reduce maladaptive weight-management practice s in women ( University females , N=24 ) with sub- clinical levels of eating pathology ; and ( b ) whether its implementation reduces the risk of developing more severe eating pathology across time . Particip Output:	Intervention and participant characteristics did not predict success in decreasing depressive symptoms . Conclusions Indicated prevention and early intervention programs targeting eating disorder symptoms are limited in their success in decreasing concurrent depressive symptoms .
MS22157	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Abstract Objective : Atovaquone plus proguanil is a new , well-tolerated and highly effective antimalarial drug . In order to protect it from the development of resistance , it may be deployed in combination with an artemisinin derivative . To investigate whether artesunate affects the pharmacokinetics of atovaquone plus proguanil , and to provide preliminary information regarding the tolerability of the triple drug combination ( artesunate plus atovaquone plus proguanil ) , a cross over study was conducted in adult volunteers . Methods : Twelve healthy Karen adults were r and omised to receive atovaquone-proguanil ( 1000/400 mg ) with or without artesunate ( 250 mg ) and , at least 90 days later , the study was repeated . Blood was sample d over a 10-day period . Results : The three-drug combination was well tolerated . Artesunate did not alter the pharmacokinetic properties of atovaquone and proguanil ( maximum plasma concentrations : 13.02 μg/ml and 742 ng/ml ; elimination half-lives : 42.2 h and 14.4 h ; oral plasma clearance estimates : 90 ml/h/kg and 710 ml/h/kg ; and apparent volumes of distribution : 4.9 l/kg and 14.5 l/kg , respectively ) . There was also no effect of artesunate on the biotransformation of proguanil to cycloguanil . The pharmacokinetic variables were similar to those reported previously for the individual drugs . Conclusion : Artesunate does not influence atovaquone or proguanil pharmacokinetics . The triple-drug combination of atovaquone and proguanil and artesunate was well tolerated The efficacy of artemether and artemether followed by mefloquine was evaluated in 45 pregnant women with drug resistant Plasmodium falciparum malaria during the second and third trimesters . There was prompt clinical response to both treatment regimens . The parasite and fever clearance times and the cure rate were similar in both groups . Except for the correlation between initial parasite density and fever clearance time in the artemether-mefloquine group , there was no correlation between initial parasite density and parasite or fever clearance times in the two groups . Similarly , there was no correlation between parasite and fever clearance . Both treatment regimens were well tolerated . All newborn babies of the participating women were normal at birth . Physical and neurodevelopmental assessment of the newborn babies followed up for a period varying between 6 and 36 months were within normal limits . Artemether alone or with mefloquine are effective and do not produce undue deleterious effects in pregnant patients with drug-resistant falciparum malaria during the second and third trimesters To compare the effectiveness and safety of quinine sulfate and artesunate with mefloquine for treating second trimester pregnancy in women who suffered from Plasmodium falciparum malaria . The prospect i ve study was done in Srisangwal Hospital , Mae Hong Son , Thail and . Sixty , second to third trimester pregnant patients with P. falciparum infection , were recruited at r and om . They received either quinine sulfate 10 mg/kg/day for at least 7 days , 29 women ( group I ) , or oral artesunate 2 mg/kg as the first dose , 1 mg/kg every 12 hours orally for at least 5 days together with split doses of mefloquine , 15 mg/kg and 6 hours later 10 mg/kg orally 1 day after artesunate was stopped , 28 women ( group II ) . Three cases ( 5 % ) were lost to follow-up before delivery , one case in group I and two cases in group II . After treatment , the mean hematocrit of group I was significantly less than group II ( p = 0.000 ) . The PCT ( parasite clearance time ) and FCT ( fever clearance time ) of group II were significantly shorter than group I ( p = 0.000 ) . None of the patients in both groups had recrudescences within 28 days . Group I had more adverse effects than group II . No adverse neurological effects in pregnancy were found in both groups . The calcification of placenta and IUGR ( Intrauterine growth retard ) were not different between the two groups ( p = 0.964 , 0.363 respectively ) . The PCT was not different between the calcified placenta group and normal placenta group ( p = 0.058 ) , but the TTPP ( Total time of parasite presentation ) was ( p = 0.000 ) . TTPP related to low birth weight and low apgar score at 1 minute might be the cause ( p = 0.000 , 0.000 F = 5.261 , 21.627 respectively ) . TTPP and PCT related to neonatal blood pH and caused low neonatal blood pH ( p = 0.000 , 0.001 F = 24.351 , 11.162 respectively ) . The physical and neurological development of the babies at 2 , 4 , 6 and 12 months follow-up , were normal and there were no congenital abnormalities in either group . TTPP relating to fetal outcome , the longer the TTPP , the worse the fetal outcome , so we should diagnose early and treat P. falciparum malaria in pregnancy to prevent fetal jeopardy . Artesunate with mefloquine could shorten the PCT more than quinine sulfate in pregnancy , so the fetal outcome was better than that of quinine sulfate . In cases of prolonged infection before treatment , artesunate might be the alternative treatment of P. falciparum malaria in pregnancy . However , its safety should be carefully studied further with a larger sample size Objective New anti-malarial regimens are urgently needed in sub-Saharan Africa because of the increase in drug resistance . We investigated the safety and efficacy of azithromycin or artesunate combined with sulfadoxine-pyrimethamine used for treatment of malaria in pregnant women in Blantyre , Malawi . Methods / Findings This was a r and omized open-label clinical trial , conducted at two rural health centers in Blantyre district , Malawi . A total of 141 pregnant women with uncomplicated Plasmodium falciparum malaria were recruited and r and omly allocated to 3 treatment groups : sulfadoxine-pyrimethamine ( SP ; 3 tablets , 500 mg sulfadoxine and 25 mg pyrimethamine per tablet ) ; SP plus azithromycin ( 1 g/day × 2 days ) ; or SP plus artesunate ( 200 mg/day × 3 days ) . Women received two doses administered at least 4 weeks apart . Heteroduplex tracking assays were performed to distinguish recrudescence from new infections . Main outcome measures were incidence of adverse outcomes , parasite and fever clearance times and recrudescence rates . All treatment regimens were well tolerated . Two women vomited soon after ingesting azithromycin . The parasite clearance time was significantly faster in the SP-artesunate group . Recrudescent episodes of malaria were less frequent with SP-azithromycin [ Hazard Ratio 0.19 ( 95 % confidence interval 0.06 to 0.63 ) ] and SP-artesunate [ Hazard Ratio 0.25 ( 95 % confidence interval 0.10 to 0.65 ) ] compared with SP monotherapy . With one exception ( an abortion in the SP-azithromycin group ) , all adverse pregnancy outcomes could be attributed to known infectious or obstetrical causes . Because of the small sample size , the effect on birth outcomes , maternal malaria or maternal anemia could not be evaluated . Conclusions Both SP-artesunate and SP-azithromycin appeared to be safe , well tolerated and efficacious for the treatment of malaria during pregnancy . A larger study is needed to determine their safety and efficacy in preventing poor birth outcomes . Trial Registration ClinialTrials.gov OBJECTIVE : To investigate the pharmacokinetics , safety and efficacy of the recommended 3-day treatment regimen of Malarone in third-trimester pregnant women with acute uncomplicated falciparum malaria . METHODS : Twenty-six pregnant women in their third trimester ( gestational age : 24–34 weeks ) with acute uncomplicated Plasmodium falciparum malaria who fulfilled the enrollment criteria were recruited from the antenatal clinics of Mae Sot Hospital , Tak Province , Thail and , ( n=8 ) and the Tropical Diseases Research Centre , Ndola , Zambia ( n=18 ) . Patients were treated with four Malarone tablets ( GlaxoSmithKline : each tablet contains 250 mg atovaquone and 100 mg proguanil ) once daily for 3 consecutive days . Blood sample s were taken for pharmacokinetic investigations of atovaquone , proguanil , and cycloguanil up to 288 h ( day 14 ) after the last dose . Urine sample s were collected for the evaluation of proguanil and cycloguanil 0–8 , 8–16 , 16–24 and 24–48 h after the last dose . Efficacy assessment s included the clinical and parasitological evaluation of mothers and newborns . Adverse events were evaluated at each visit to the antenatal clinics . RESULTS : Malarone appeared to be effective and well tolerated when used for the treatment of falciparum malaria in pregnant women . All patients showed prompt clinical improvement and the disappearance of parasitaemia after treatment . There were no serious adverse effects or unexpected adverse effects and no stillbirths or spontaneous abortions . The plasma concentration-time profiles of atovaquone and proguanil in most cases were best characterised by the two-compartment open model with zero-order input with/without absorption lag time and first-order elimination . There were no significant differences in any of the pharmacokinetic parameters of atovaquone , proguanil or cycloguanil between patients from Thail and and Zambia . For atovaquone , a Cmax of 1.33–8.33 μg/ml was reached at 2.0–9.3 h after the last dose on day 2 . V/F , CL/F and t1/2β were 6.9–39.5 l/kg , 83–384 ml/h/kg , and 57.8–130.8 h , respectively . The Cmax and tmax values for proguanil versus cycloguanil were 383–918 versus 0–129 ng/ml and 3.3–8.6 versus 3–12 h , respectively . V/F , CL/F , and t1/2β values for proguanil were 10.7–34.0 l/kg , 431–1,662 ml/h/kg and 11.2–30.3 h. The CLR-CG , t1/2z , CG , proguanil/cycloguanil metabolic ratios , AUC ratios for proguanil to cycloguanil ( AUCPG/CG ) were 107.2–1,001 ml/h/kg , 5–95 ml/h/kg , 7.8–20.7 h , 5–57 , and 4.7–20.2 , respectively . CONCLUSION : The pharmacokinetics of atovaquone and cycloguanil appeared to be influenced by the pregnancy status , result ing in an decrease in the Cmax and AUC of approximately twofold Malaria during pregnancy is associated with maternal and fetal morbidity and mortality . In order to minimize the burden , sulfadoxine – pyrimethamine ( SP ) is widely used in Africa as an intermittent preventive treatment of malaria in pregnancy ( IPTp ) . However , only limited data are available on the pharmacokinetics of sulfadoxine and pyrimethamine during pregnancy . We conducted a prospect i ve , self‐matched , multicenter study of 98 pregnant women in four African countries in order to determine the effects of pregnancy on SP pharmacokinetics . After adjusting for the effects of potential confounders , blood concentrations ( associated with therapeutic efficacy ) of pyrimethamine were higher ( geometric mean ratio ( GMR ) 1.33 ; 95 % confidence interval ( CI ) 1.18–1.51 ; P < 0.001 ) and those of sulfadoxine were lower ( GMR 0.91 ; 95 % CI 0.84–0.98 ; P = 0.013 ) on day 7 after SP administration during pregnancy than after the postpartum period . SP pharmacokinetic parameters differed significantly among the study sites . Given the inconsistency of changes in pharmacokinetic parameters between sulfadoxine and pyrimethamine as well as among the study sites , it is not possible to recommend any dose adjustment to prolong the therapeutic life span of the fixed dose combination of SP for IPTp on the basis of our study findings BACKGROUND There is no safe , practical , and effective treatment for pregnant women infected with multidrug-resistant Plasmodium falciparum . METHODS We recruited pregnant Karen women in the second or third trimesters of pregnancy who had uncomplicated falciparum malaria for a r and omized , open-label trial with a restricted sequential trial design of 7 days of supervised quinine ( Output:	Comparison of the available studies showed lower maximum concentrations ( Cmax ) and exposure ( AUC ) of dihydroartemisinin , the active metabolite of all artemisinin derivatives , after oral administration of artemether , artesunate and dihydroartemisinin in pregnant women . Low day 7 concentrations were commonly seen in lumefantrine studies , indicating a low exposure and possibly reduced efficacy . The influence of pregnancy on amodiaquine and piperaquine seemed not to be clinical ly relevant . Sulfadoxine plasma concentration was significantly reduced and clearance rates were higher in pregnancy , while pyrimethamine and mefloquine need more research as no general conclusion can be drawn based on the available evidence . For atovaquone , the available data showed a lower maximum concentration and exposure . Finally , the maximum concentration of cycloguanil , the active metabolite of proguanil , was significantly lower , possibly compromising the efficacy . Conclusion These findings suggest that re assessment of the dose of the artemisinin derivate and some components of ACT are necessary to ensure the highest possible efficacy of malaria treatment in pregnant women .
MS22158	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: CONTEXT Cannabis sativa use can impair verbal learning , provoke acute psychosis , and increase the risk of schizophrenia . It is unclear where C. sativa acts in the human brain to modulate verbal learning and to induce psychotic symptoms . OBJECTIVES To investigate the effects of 2 main psychoactive constituents of C. sativa , Delta9-tetrahydrocannabinol ( Delta9-THC ) and cannabidiol , on regional brain function during verbal paired associate learning . DESIGN Subjects were studied on 3 separate occasions using a block design functional magnetic resonance imaging paradigm while performing a verbal paired associate learning task . Each imaging session was preceded by the ingestion of Delta9-THC ( 10 mg ) , cannabidiol ( 600 mg ) , or placebo in a double-blind , r and omized , placebo-controlled , repeated- measures , within-subject design . SETTING University research center . PARTICIPANTS Fifteen healthy , native English-speaking , right-h and ed men of white race/ethnicity who had used C. sativa 15 times or less and had minimal exposure to other illicit drugs in their lifetime . MAIN OUTCOME MEASURES Regional brain activation ( blood oxygen level-dependent response ) , performance in a verbal learning task , and objective and subjective ratings of psychotic symptoms , anxiety , intoxication , and sedation . RESULTS Delta9-Tetrahydrocannabinol increased psychotic symptoms and levels of anxiety , intoxication , and sedation , whereas no significant effect was noted on these parameters following administration of cannabidiol . Performance in the verbal learning task was not significantly modulated by either drug . Administration of Delta9-THC augmented activation in the parahippocampal gyrus during blocks 2 and 3 such that the normal linear decrement in activation across repeated encoding blocks was no longer evident . Delta9-Tetrahydrocannabinol also attenuated the normal time-dependent change in ventrostriatal activation during retrieval of word pairs , which was directly correlated with concurrently induced psychotic symptoms . In contrast , administration of cannabidiol had no such effect . CONCLUSION The modulation of mediotemporal and ventrostriatal function by Delta9-THC may underlie the effects of C. sativa on verbal learning and psychotic symptoms , respectively Output:	Limited research carried out in humans tends to support the evidence that chronic cannabis use reduces levels of glutamate-derived metabolites in both cortical and subcortical brain areas . Research in animals tends to consistently suggest that Δ9-THC depresses glutamate synaptic transmission via CB1 receptor activation , affecting glutamate release , inhibiting receptors and transporters function , reducing enzyme activity , and disrupting glutamate synaptic plasticity after prolonged exposure
MS22159	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Whole‐body vibration ( WBV ) training is commonly practice d and may enhance peripheral blood flow . Here , we investigated muscle morphology and acute microcirculatory responses before and after a 6‐week resistive exercise training intervention without ( RE ) or with ( RVE ) simultaneous whole‐body vibrations ( 20 Hz , 6 mm peak‐to‐peak amplitude ) in 26 healthy men in a r and omized , controlled parallel‐ design study . Total haemoglobin ( tHb ) and tissue oxygenation index ( TOI ) were measured in gastrocnemius muscle ( GM ) with near‐infrared spectroscopy ( NIRS ) . Whole‐body oxygen consumption ( VO2 ) was measured via spirometry , and skeletal muscle morphology was determined in soleus ( SOL ) muscle biopsies . Our data reveal that exercise‐induced muscle deoxygenation both before and after 6 weeks training was similar in RE and RVE ( P = 0·76 ) , although VO2 was 20 % higher in the RVE group ( P<0·001 ) . The RVE group showed a 14%‐point increase in reactive hyperaemia ( P = 0·007 ) and a 27 % increase in blood volume ( P<0·01 ) in GM after 6 weeks of training . The number of capillaries around fibres was increased by 15 % after 6 weeks training in both groups ( P<0·001 ) with no specific effect of superimposed WBV ( P = 0·61 ) . Neither of the training regimens induced fibre hypertrophy in SOL . The present findings suggest an increased blood volume and vasodilator response in GM as an adaptation to long‐term RVE , which was not observed after RE alone . We conclude that RVE training enhances vasodilation of small arterioles and possibly capillaries . This effect might be advantageous for muscle thermoregulation and the delivery of oxygen and nutrients to exercising muscle and removal of carbon dioxide and metabolites Abstract The aim of the study was to compare the effect of an unsupervised whole body vibration ( WBV ) training and two different supervised multi- purpose exercise programmes , with and without WBV , on body composition , functional fitness and self-reported well-being in middle-aged adults . Fifty-four healthy participants ( age 48.6 ± 6.7 years ) were r and omly assigned to a vibration group ( VG ) , a multi- purpose exercise group ( MG ) and a multi- purpose exercise with vibration group ( VMG ) and trained 3 days a week for 4 months . VG performed a st and ardised unsupervised WBV protocol , MG a supervised multi- purpose exercise and VMG a multi- purpose exercise including vibration . After training , drop out was significantly higher in VG group ( P = 0.016 ) when compared to VMG group . In both MG and VMG , body composition , sit-up , push-up , sit and reach , agility test , hopping test and self-reported general health significantly improved ( P < 0.05 ) . No additive effects were generated by the vibration stimulus . Percentage of body fat and agility test in VG had a significant opposite trend compared to VMG group ( P < 0.05 ) . In summary , an unsupervised WBV training should not be chosen for training protocol . However , positive effects on physical fitness and the best results in adherence could be achieved integrating WBV practice into a multi- purpose exercise training This study compared the rate of muscle temperature ( Tm ) increase during acute whole-body vibration ( WBV ) , to that of stationary cycling and passive warm-up . Additionally we wanted to determine if the purported increase in counter-movement jump and peak power cycling from acute WBV could be explained by changes in muscle temperature . Eight active participants volunteered for the study , which involved a rest period of 30 min to collect baseline measures of muscle , core , skin temperature , heart rate ( HR ) , and thermal leg sensation ( TLS ) , which was followed by three vertical jumps and 5 s maximal cycle performance test . A second rest period of 40 min was enforced followed by the intervention and performance tests . The change in Tm elicited during cycling was matched in the hot bath and WBV interventions . Therefore cycling was performed first , proceeded by , in a r and om order of hot bath and acute WBV . The rate of Tm was significantly greater ( P < 0.001 ) during acute WBV ( 0.30 ° C min−1 ) compared to cycle ( 0.15 ° C min−1 ) and hot bath ( 0.09 ° C min−1 ) however there was no difference between the cycle and hot bath , and the metabolic rate was the same in cycling and WBV ( 19 mL kg−1 min−1 ) . All three interventions showed a significant ( P < 0.001 ) increase in countermovement jump peak power and height . For the 5 s maximal cycle test ( MIC ) there were no significant differences in peak power between the three interventions . In conclusion , acute WBV elevates Tm more quickly than traditional forms of cycling and passive warm-up . Given that all three warm-up methods yielded the same increase in peak power output , we propose that the main effect is caused by the increase in Tm OBJECTIVE The aim of this study was to evaluate the effect on spasticity , muscle strength and motor performance after 8 weeks of whole-body vibration training compared with resistance training in adults with cerebral palsy . METHODS Fourteen persons with spastic diplegia ( 21 - 41 years ) were r and omized to intervention with either whole-body vibration training ( n=7 ) or resistance training ( n=7 ) . Pre- and post-training measures of spasticity using the modified Ashworth scale , muscle strength using isokinetic dynamometry , walking ability using Six-Minute Walk Test , balance using Timed Up and Go test and gross motor performance using Gross Motor Function Measure were performed . RESULTS Spasticity decreased in knee extensors in the whole-body vibration group . Muscle strength increased in the resistance training group at the velocity 30 degrees /s and in both groups at 90 degrees /s . Six-Minute Walk Test and Timed Up and Go test did not change significantly . Gross Motor Function Measure increased in the whole-body vibration group . CONCLUSION These data suggest that an 8-week intervention of whole-body vibration training or resistance training can increase muscle strength , without negative effect on spasticity , in adults with cerebral palsy Objective : To examine the effectiveness of whole body vibration ( WBV ) on tone , muscle force , sensation and functional performance in people with multiple sclerosis . Design : A r and omized cross-over pilot study . Setting : Revive MS Support Therapy Centre . Glasgow , UK . Subjects : Sixteen people with multiple sclerosis were r and omly allocated to one of two groups . Intervention : Group 1 received four weeks of whole body vibration plus exercise three times per week , two weeks of no intervention and then four weeks of exercise alone three times per week . Group 2 were given the two treatment interventions in the reverse order to group 1 . Main measures : Ten-metre walk , Timed Up and Go Test , Modified Ashworth Scale , Multiple Sclerosis Spasticity Scale ( MSSS-88 ) , lower limb muscle force , Nottingham Sensory Assessment and Multiple Sclerosis Impact Scale ( MSIS-29 ) were used before and after intervention . Results : The exercise programme had positive effects on muscle force and well-being , but there was insufficient evidence that the addition of whole body vibration provided any further benefit . The Modified Ashworth Scale was generally unaffected by either intervention , although , for each group , results from the MSSS-88 showed whole body vibration and exercises reduced muscle spasms ( P = 0.02 ) . Although results for the 10-m walk and Timed Up and Go Test improved , this did not reach statistical significance ( P = 0.56 ; P = 0.70 , respectively ) . For most subjects sensation was unaffected by whole body vibration . Conclusion : Exercise may be beneficial to those with multiple sclerosis , but there is limited evidence that the addition of whole body vibration provides any additional improvements . Further larger scale studies into the effects of whole body vibration in people with multiple sclerosis are essential OBJECTIVE To evaluate the effects of whole-body vibration ( WBV ) training in individuals after stroke . DESIGN A double-blind r and omized controlled study with assessment s pre- and posttraining . SETTING A university hospital rehabilitation department . PARTICIPANTS Participants ( N=31 ; mean age ± SD , 62±7 y ; 6 - 101 mo poststroke ) were r and omized to an intervention group or a control group . INTERVENTIONS Supervised WBV training ( 2 sessions/wk for 6wk ; 12 repetitions of 40 - 60s WBV per session ) . The intervention group trained on a vibrating platform with a conventional amplitude ( 3.75 mm ) and the control group on a " placebo " vibrating platform ( 0.2 mm amplitude ) ; the frequency was 25Hz on both platforms . All participants and examiners were blinded to the amplitudes of the 2 platforms . MAIN OUTCOME MEASURES Primary outcome measures were isokinetic and isometric knee muscle strength ( dynamometer ) . Secondary outcome measures were balance ( Berg Balance Scale ) , muscle tone ( Modified Ashworth Scale ) , gait performance ( Timed Up & Go , comfortable gait speed , fast gait speed , and six-minute walk tests ) , and perceived participation ( Stroke Impact Scale ) . RESULTS There were no significant differences between the 2 groups after the WBV training . Significant but small improvements ( P<.05 ) in body function and gait performance were found within both groups , but the magnitude of the changes was in the range of normative variation . CONCLUSIONS Six weeks of WBV training on a vibration platform with conventional amplitude was not more efficient than a placebo vibrating platform . Therefore , the use of WBV training in individuals with chronic stroke and mild to moderate disability is not supported Objective : To investigate the effects of a single session of whole body vibration training on ankle plantarflexion spasticity and gait performance in chronic stroke patients . Design : R and omized controlled trial . Setting : Rehabilitation unit in university hospital . Participants : Thirty subjects with chronic stroke were r and omized into either a control group ( n = 15 ) or a group receiving a single session of whole body vibration ( n = 15 ) . Intervention : The intervention group was actually treated with whole body vibration while the control group was treated with placebo treatment . Main measures : The spastic changes were measured clinical ly and neurophysiologically . Subjective evaluation of ankle spasticity was performed via a visual analogue scale . Gait performances were evaluated by the timed up and go test , 10-meter walk test and cadence . A forceplate was used for measuring foot pressure . Results : The changes between whole body vibration and control groups were significantly different in Modified Ashworth Scale ( 1.33 , 95 % confidence interval ( CI ) = 1.06~1.60 ) . The Hmax/Mmax ratio ( 0.14 , 95 % CI = 0.01~0.26 ) and visual analogue scale ( 1.87 , 95 % CI = 1.15~2.58 ) were significantly decreased . Whole body vibration could significantly improve gait velocity , timed up and go test ( 6.03 , 95 % CI = 3.17~8.89 ) and 10-meter walk test ( 1.99 , 95 % CI = 0.11~3.87 ) . The uneven body weight posture on bilateral feet was also improved after vibration . Conclusion : These results suggest that a single session of whole body vibration training can reduce ankle plantarflexion spasticity in chronic stroke patients , thereby potentially increasing ambulatory capacity The effect of whole‐body vibration dosage on leg blood flow was investigated . Nine healthy young adult males completed a set of 14 r and om vibration and non‐vibration exercise bouts whilst squatting on a Galileo 900 plate . Six vibration frequencies ranging from 5 to 30 Hz ( 5 Hz increments ) were used in combination with a 2·5 mm and 4·5 mm amplitude to produce twelve 1‐min vibration bouts . Subjects also completed two 1‐min bouts where no vibration was applied . Systolic and diastolic diameters of the common femoral artery and blood cell velocity were measured by an echo Doppler ultrasound in a st and ing or rest condition prior to the bouts and during and after each bout . Repeated measures MANOVAs were used in the statistical analysis . Compared with the st and ing condition , the exercise bouts produced a four‐fold increase in mean blood cell velocity ( P<0·001 ) and a two‐fold increase in peak blood cell velocity ( P<0·001 ) . Compared to the non‐vibration bouts , frequencies of 10–30 Hz increased mean blood cell velocity by approximately 33 % ( P<0·01 ) whereas 20–30 Hz increased peak blood cell velocity by approximately 27 % ( P<0·01 ) . Amplitude was additive to frequency but only achieved significance at 30 Hz ( P<0·05 ) . Compared with the st and ing condition , squatting alone produced significant increases in mean and peak blood cell velocity ( P<0·001 ) . The results show leg blood flow increased during the squat or non‐vibration bouts and systematic ally increased with frequency in the vibration bouts BACKGROUND Whole-body vibration ( WBV ) has been used in older adults to improve bone health and neuromuscular function , and may have potential applications for stroke patients . AIM To investigate the effects of WBV on bone turnover , leg muscle strength , motor function , and spasticity among chronic stroke patients . DESIGN R and omized controlled trial ( RCT ) . SETTING Community . POPULATION Eighty-two chronic stroke patients . METHODS The experimental group under Output:	Otherwise , the results revealed no consistent benefits on spasticity in other neurological conditions studied . There is little evidence that change in spasticity was related to change in functional performance . There is insufficient evidence to support or refute the notion that whole-body vibration can reduce spasticity in stroke , spinocerebellar ataxia or multiple sclerosis
MS22160	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: PURPOSE Peripheral T-cell lymphomas ( PTCLs ) are a heterogeneous group of malignancies characterized by a poor prognosis . We performed a pilot study to investigate the role of reduced-intensity conditioning ( RIC ) followed by allogeneic stem-cell transplantation in relapsed or refractory PTCLs . PATIENTS AND METHODS We have conducted a phase II trial on 17 patients receiving salvage chemotherapy followed by RIC and allogeneic transplantation of hematopoietic cells . The RIC regimen consisted of thiotepa , fludarabine , and cyclophosphamide . The acute graft-versus-host disease prophylaxis consisted of cyslosporine and short course methotrexate . RESULTS Patients had a median age of 41 years ( range , 23 to 60 years ) . Two patients were primary chemorefractory , and 15 had relapsed disease ; eight patients ( 47 % ) had a disease relapse after an autologous transplantation . After a median follow-up of 28 months from the day of study entry ( range , 3 to 57 months ) , 14 of 17 patients were alive ( 12 in complete remission , one in partial remission , and one with stable disease ) , two died as a result of progressive disease , and one died as a result of sepsis concomitant to acute graft-versus-host disease . The estimated 3-year overall and progression-free survival rates were 81 % ( 95 % CI , 62 % to 100 % ) and 64 % ( 95 % CI , 39 % to 89 % ) , respectively . The estimated probability of nonrelapse mortality at 2 years was 6 % ( 95 % CI , 1 % to 17 % ) . Donor lymphocyte infusions induced a response in two patients progressing after allografting . CONCLUSION RIC followed by allogeneic stem-cell transplantation is feasible , has a low treatment-related mortality , and seems to be a promising salvage treatment for relapsed PTCL . These findings suggest that the existence of a graft-versus-T-cell lymphoma effect T-cell NHL represent 10 - 15 % of all malignant lymphomas making systematic prospect i ve clinical trials difficult . Therefore , the prognostic significance of the T-cell phenotype has been a matter of controversy in recent years . In a retrospective analysis of 681 patients ( pts ) with NHL accrued from 1992 to 1997 at a single institution , 66 patients with T-cell NHL were identified . According to the REAL classification , histologies were as follows : 28 peripheral T-cell lymphomas ( PTCL ) , 19 large cell anaplastic lymphoma ( LCAL ) , 12 precursor lymphoblastic lymphoma ( Lb ) , and seven AILD . Multiagent anthracycline containing regimens were used as initial therapy in 91 % of cases . T-cell NHL represent 9.8 % of all NHL patients at our institution accrued over a 6-year period . Overall response rate was 76 % , 21 % had progressive disease and 3 % died during first line treatment . Mean overall survival ( OS ) was 8.22 ± 0.94 years . There was a significant difference in OS between the four different histological subgroups ( log rank P = 0.0288 ) . LCAL : mean OS 11.05 ± 1.55 years ( 95 % CI 8.00 - 14.09 ) ; LB : mean OS 7.09 ± 1.40 years ( 95 % CI 4.33 - 9.84 ) ; PTCL : mean 6.62 ± 1.17 years ( 95 % CI 4.33 - 8.90 ) ; AILD : 1.54 ± 0.44 years ( 95 % CI 0.67 - 2.40 ) . OS was also significantly different for patients classified according to the International Prognostic Index (IPI)-score ( log rank P = 0.002 ) . Mean OS for patients with low risk , intermediate low risk , intermediate high risk and high risk was 10.46 ± 1.02 , 6.46 ± 1.79 , 4.50 ± 1.20 and 1.15 ± 0.46 years , respectively . Univariate analysis ( log-rank test ) for prognostic factors also revealed elevated LDH , B-symptoms and extranodal involvement as significant factors for OS . The presence of bulky disease ( > 7.5 cm ) , advanced stage III/IV and bone marrow involvement did not influence OS . In conclusion , it is evident that histological subtype and IPI-score have a strong prognostic impact on OS in pts with T-cell NHL . Thus , the distribution of risk factors in patients with T-cell NHL may be more important for OS than T-cell histology per se PURPOSE Aggressive T-cell lymphomas ( ATCLs ) represent 10 % to 15 % of non-Hodgkin 's lymphomas ( NHLs ) in adults . ATCLs show a worse prognosis than B-cell lymphomas . PATIENTS AND METHODS On behalf of the Société Française de Greffe de Moëlle et de Thérapie Cellulaire , we conducted a retrospective analysis including 77 ATCL patients who underwent allogeneic stem-cell transplantation ( alloSCT ) . RESULTS The different diagnosis included anaplastic large-cell lymphoma ( ALCL ; n = 27 ) , peripheral T-cell lymphoma not otherwise specified ( PTCL-NOS ; n = 27 ) , angioimmunoblastic T-cell lymphoma ( AITL ; n = 11 ) , hepatosplenic gamma/delta lymphoma ( HSL ; n = 3 ) , T-cell granular lymphocytic leukemia ( T-GLL ; n = 1 ) , nasal natural killer (NK)/T-cell lymphoma ( nasal-NK/L ; n = 3 ) or non-nasal NK/T-cell lymphoma ( non-nasal-NK/L ; n = 2 ) , enteropathy-type T-cell ( n = 1 ) , and human T-lymphotropic virus (HTLV)-1 lymphoma ( n = 2 ) . Fifty-seven patients received a myeloablative conditioning regimen . Donors were human leukocyte antigen (HLA)-matched in 70 cases and related in 60 cases . Thirty-one patients were in complete remission ( CR ) at the time of alloSCT , whereas 26 were in partial response ( PR ) . Five-year toxicity-related mortality ( TRM ) incidence was 33 % ( 95 % CI , 24 % to 46 % ) . The 5-year overall survival ( OS ) and event-free survival ( EFS ) rates were 57 % ( 95 % CI , 45 % to 68 % ) and 53 % ( 95 % CI , 41 % to 64 % ) , respectively . In multivariate analysis , chemoresistant disease ( stable , refractory , or progressing disease ) at the time of alloSCT and the occurrence of severe grade 3 to 4 acute graft-versus-host disease ( aGVHD ) were the strongest adverse prognostic factors for OS ( P = .03 and .03 , respectively ) . Disease status at transplantation significantly influenced the 5-year EFS ( P = .003 ) , and an HLA-mismatched donor increased TRM ( P = .04 ) . CONCLUSION We conclude that alloSCT is a potentially efficient therapy for NK/T lymphomas and is worth further investigation through prospect i ve clinical trials PURPOSE Systemic peripheral T-cell lymphomas ( PTCLs ) respond poorly to conventional therapy . To evaluate the efficacy of a dose-dense approach consoli date d by up-front high-dose chemotherapy ( HDT ) and autologous stem-cell transplantation ( ASCT ) in PTCL , the Nordic Lymphoma Group ( NLG ) conducted a large prospect i ve phase II study in untreated systemic PTCL . This is the final report , with a 5-year median follow-up , of the NLG-T-01 study . PATIENTS AND METHODS Treatment-naive patients with PTCL age 18 to 67 years ( median , 57 years ) were included . Anaplastic lymphoma kinase ( ALK ) -positive anaplastic large-cell lymphoma ( ALCL ) was excluded . An induction regimen of six cycles of biweekly CHOEP ( cyclophosphamide , doxorubicin , vincristine , etoposide , and prednisone ) was administered ( in patients age > 60 years , etoposide was omitted ) . If in complete or partial remission , patients proceeded to consolidation with HDT/ASCT . RESULTS Of 166 enrolled patients , 160 had histopathologically confirmed PTCL . The majority presented with advanced-stage disease , B symptoms , and elevated serum lactate dehydrogenase . A total of 115 underwent HDT/ASCT , with 90 in complete remission at 3 months post-transplantation . Early failures occurred in 26 % . Treatment-related mortality was 4 % . At 60.5 months of median follow-up , 83 patients were alive . Consoli date d 5-year overall and progression-free survival ( PFS ) were 51 % ( 95 % CI , 43 % to 59 % ) and 44 % ( 95 % CI , 36 % to 52 % ) , respectively . Best results were obtained in ALK-negative ALCL . CONCLUSION Dose-dense induction followed by HDT/ASCT was well tolerated and led to long-term PFS in 44 % of treatment-naive patients with PTCL . This represents an encouraging outcome , particularly considering the high median age and adverse risk profile of the study population . Therefore , dose-dense induction and HDT/ASCT are a rational up-front strategy in transplantation-eligible patients with PTCL Output:	They concluded that ASCT done as part of frontline treatment for PTCL does not improve overall survival . The results of the meta- analysis reported in this issue of Acta Haematologica do not support the use of ASCT as part of the initial treatment of PTCL .
MS22161	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To compare the clinical effects of laterally wedged insoles and neutrally wedged insoles ( used as control ) in patients with medial femoro-tibial knee osteoarthritis ( OA ) . DESIGN 6-month prospect i ve r and omized controlled study . PATIENTS out patients with painful medial femoro-tibial knee OA . OUTCOME MEASURES patient 's overall assessment of disease activity ( 5 grade scale ) , WOMAC index subscales and concomitant treatments . STATISTICAL ANALYSIS Performed as an intention-to-treat analysis . Main criterion : improvement in the patient 's assessment of activity ( defined as a reduction of 1 grade or more at month 6 compared to baseline , and no intraarticular injection or lavage during the study ) . Secondary criteria for assessment : ( a ) improvement in the patient 's assessment of activity at months 1 and 3 compared to baseline , ( b ) improvement in the WOMAC subscales at months 1 , 3 and 6 , compared to baseline ( defined as an improvement of at least 30 % , and no intraarticular injection or lavage during the study ) and ( c ) concomitant therapies ( analgesics and NSAIDs ) . RESULTS The baseline characteristics of the 156 recruited patients ( 41 males , 115 females , mean age 64.8 years ) were not different in the two treatment groups . At months 1 , 3 and 6 the percentages of patients with improvement in assessment of disease activity , in WOMAC pain , joint stiffness , and physical functioning subscales were similar in the two groups . The number of days with NSAIDs intake during the previous 3 months was decreased at month 6 compared with baseline in the group furnished with laterally wedged insoles ( 14.1 days+/-28 vs 9.9 days+/-27 , P=0.04 , Wilcoxon paired test ) , while it remained unchanged in the other group ( 15.5 days+/-24 vs 15+/-28 , P=0.56 ) . Compliance and tolerance were satisfactory . Compliance was different between the two groups at month 6 , with a greater frequency of patients who wore insoles permanently in the laterally wedged insole group than in the other group ( 87.8 % vs 74.3%;P=0.032 ) . CONCLUSION This study failed to demonstrate a relevant short-term symptomatic effect of laterally-wedged insoles in medial femoro-tibial OA . However , the decrease in NSAIDs consumption together with better compliance in the treated group are in favor of a beneficial effect of laterally-wedged insoles in medial femoro-tibial OA OBJECTIVE To assess the effect of an insole with subtalar strapping on patients with medial compartment osteoarthritis ( OA ) of the knee . METHODS Novel lateral wedged insoles with elastic subtalar strapping ( the subtalar strapping support group ) and ankle supporters with a lateral wedged heel insert ( the sock-type ankle support group ) were prepared . Eighty-eight female out patients with knee OA were treated with 1 of the 2 insoles for 8 weeks . Femorotibial angle was assessed by st and ing radiographs with and without unilateral insole use for each subject . Symptoms of knee OA were evaluated according to the severity index of Lequesne et al at baseline and at the final assessment . RESULTS Participants wearing the insole with subtalar strapping ( n = 42 ) demonstrated significantly decreased femorotibial angle ( an average of change : -3.1 degrees + /- 2.5 degrees , P < 0.0001 ) , but a significant difference was not found in the sock-type ankle support group ( n = 46 ; -0.4 degrees + /- 1.1 degrees , P > 0.05 ) . In the subtalar strapping support group , pain during bed rest with full extension of the knee ( P < 0.0001 ) , pain after getting up ( P = 0.04 ) , pain on getting up from a seated position ( P = 0.021 ) , maximum distance walked ( P = 0.009 ) , and aggregate severity score ( P < 0.0001 ) were significantly improved compared with baseline . In contrast , significant symptomatic improvement was detected only in the aggregate score ( P = 0.016 ) in the sock-type ankle support group , but not in any of the 10 specific categories . CONCLUSION The lateral wedged insole with subtalar strapping induces correction of the femorotibial angle and symptomatic relief in patients with varus-deformity knee OA OBJECTIVE To assess the optimal duration of daily wear for a laterally wedged insole with subtalar strapping in subjects with medial compartment osteoarthritis of the knee ( knee OA ) . DESIGN The setting was an outpatient clinic . Eighty-one patients with knee OA were prospect ively r and omized according to birth date and to either 2 weeks of treatment with a lateral wedge with subtalar strapping for less than 5 h ( the short group ) , 5 - 10 h ( the medium group ) or greater than 10 h ( the long group ) each day , or to treatment with a subtalar strapping b and without lateral wedge ( the placebo group ) . St and ing radiographs were used to analyze the femorotibial angle for each subject , both with and without their respective orthotic device . The remission scores of Lequesne index were compared among the four groups at the conclusion . RESULTS The short ( n=21 ) , medium ( n=20 ) and long ( n=18 ) groups demonstrated a significant greater valgus correction of the femorotibial angle than the placebo group ( n=22 ) ( P<0.0001 ) . The remission score was significantly improved in the medium group compared to the placebo ( P=0.001 ) and long ( P=0.001 ) groups . CONCLUSIONS An optimal duration of insole with subtalar strapping wear for patients with varus deformity knee OA may be between 5 and 10 h each day Objective To assess the effect of lateral wedge insoles compared with flat control insoles on improving symptoms and slowing structural disease progression in medial knee osteoarthritis . Design R and omised controlled trial . Setting Community in Melbourne , Australia . Participants 200 people aged 50 or more with clinical and radiographic diagnosis of mild to moderately severe medial knee osteoarthritis . Interventions Full length 5 degree lateral wedged insoles or flat control insoles worn inside the shoes daily for 12 months . Main outcome measures Primary symptomatic outcome was change in overall knee pain ( past week ) measured on an 11 point numerical rating scale . Primary structural outcome was change in volume of medial tibial cartilage from magnetic resonance imaging scans . Secondary clinical outcomes included changes in measures of pain , function , stiffness , and health related quality of life . Secondary structural outcomes included progression of medial cartilage defects and bone marrow lesions . Results Between group differences did not differ significantly for the primary outcomes of change in overall pain ( −0.3 points , 95 % confidence intervals −1.0 to 0.3 ) and change in medial tibial cartilage volume ( −0.4 mm3 , 95 % confidence interval −15.4 to 14.6 ) , and confidence intervals did not include minimal clinical ly important differences . None of the changes in secondary outcomes showed differences between groups . Conclusion Lateral wedge insoles worn for 12 months provided no symptomatic or structural benefits compared with flat control insoles . Trial registration Australian New Zeal and Clinical Trials Registry ACTR12605000503628 and Clinical Trials.gov NCT00415259 The purpose of the study was to examine the clinical efficacy of individually prescribed laterally wedged orthoses and walking shoes in the treatment of medial knee osteoarthritis using a prospect i ve , single-blind , block-r and omized controlled design . Sixty-six subjects ( 29 males , 37 females , mean age 62.4 years , mean BMI 33.0 kg/m(2 ) ) were block-r and omized to a lateral wedge ( treatment ) or neutral ( control ) orthotic group . Both groups were issued a st and ardized walking shoe for use with the orthoses . Primary outcome measures included the pain , stiffness , and functional limitations subscales of the Western Ontario and McMaster Universities index . Secondary outcome measures included the 6-minute walk distance and pain change , and stair negotiation time and pain change . A significant interaction ( p=0.039 ) favoring the treatment group was observed for pain change during the 6-minute walk . The treatment group demonstrated significant improvements at both 1 month ( p<0.001 ) and 1 year ( p<0.001 ) compared to baseline . The control group only demonstrated significant improvements at 1 year ( p=0.017 ) . No other interactions were observed . Both groups were improved at each follow-up in the WOMAC subscales for pain ( p<0.001 ) , stiffness ( p<0.001 ) , and physical function ( p<0.001 ) . Both groups also improved in 6-minute walk test distance ( p<0.001 ) , stair negotiation test time ( p=0.004 ) , and stair negotiation test pain change ( p<0.001 ) . The results suggest that both neutral and laterally wedged orthoses may be beneficial in the management of medial knee osteoarthritis when used with walking shoes . However , the addition of lateral wedging was associated with early improvements in 6-minute walk test pain change not seen in the control group OBJECTIVE To compare the clinical effects of laterally wedged insoles and neutrally wedged insoles ( used as control ) in patients with medial femoro-tibial knee osteoarthritis . METHODS STUDY DESIGN 24-month prospect i ve r and omized controlled study . PATIENTS Out patients with painful medial femoro-tibial knee osteoarthritis . OUTCOME MEASURES Patient 's overall assessment of disease activity ( 5 grade scale ) , WOMAC index subscales and concomitant treatments . STATISTICAL ANALYSIS Performed as an intention-to-treat analysis , with the last observation carried forward ( LOCF ) . Main symptomatic criterion : Improvement in the patient 's assessment of activity ( defined as a reduction of one grade or more at the end of the study as compared to baseline , and no intra-articular injection or lavage during the 6 months previous to the last visit ) . Secondary criteria for assessment : ( a ) Changes in the WOMAC subscales at month 24 , and ( b ) concomitant therapies ( analgesics , NSAIDs and intra-articular injections or lavages ) . Structural criterion : Joint space width ( JSW ) at the narrowest point . Non-compliance was defined as intermittent or lack of insole fitting at two consecutive visits . Compliance within groups was compared by using a life table analysis technique ( Log-Rank ) . RESULTS The baseline characteristics of the 156 recruited patients ( 41 males , 115 females , mean age 64.8 years ) were not different in the 2 treatment groups . At year 2 , there was no statistically significant difference between the 2 groups concerning the percentages of patients with improvement in both global assessment of disease activity and in WOMAC subscales ( pain , stiffness , function ) . The number of days with NSAIDs intake was lower in the group with laterally wedged insoles than in the neutrally wedged group ( 71+/-173 days vs. 127+/-193 days , P=0.003 , Mann-Whitney test ) . The mean joint space narrowing rate did not differ between the two groups : 0.21+/-0.59 mm/year in the laterally wedged group vs 0.12+/-0.32 mm/year in the neutrally wedged group . Compliance and tolerance were satisfactory . Compliance was different between the 2 groups at month 24 , with a greater frequency of patients who wore insoles permanently in the laterally wedged insole group than in the other group ( 85.8 % vs 71.9 % , P=0.023 ) . CONCLUSION This study failed to demonstrate a relevant symptomatic and /or structural effect of laterally-wedged insoles in medial femoro-tibial OA . However , the reduced NSAIDs intake and the better compliance in the treatment group are in favor of a beneficial effect of laterally-wedged insoles in medial femoro-tibial OA BACKGROUND The purpose of this study was to compare a custom-made valgus-producing functional knee ( unloader ) brace , a neoprene sleeve , and medical treatment only ( control group ) with regard to their ability to improve the disease-specific quality of life and the functional status of patients who had osteoarthritis in association with a varus deformity of the knee ( varus gonarthrosis ) . METHODS The study design was a prospect i ve , parallel-group , r and omized clinical trial . Patients who had varus gonarthrosis were screened for eligibility . The criteria for exclusion included arthritides other than osteoarthritis ; an operation on the knee within the previous six months ; symptomatic disease of the hip , ankle , or foot ; a previous fracture of the tibia or femur ; morbid obesity ( a body-mass index of more than thirty-five kilograms per square meter ) ; skin disease ; peripheral vascular disease or varicose veins that would preclude use of a brace ; a severe cardiovascular deficit ; blindness ; poor English- language skills ; and an inability to apply a brace because of physical limitations such as arthritis in the h Output:	Conclusion : Quality of clinical practice guidelines for orthotic treatment of knee osteoarthritis in the Nordic region is variable .
MS22162	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objective —To compare cardiac output measured by the transoesophageal Doppler and thermodilution techniques . Design — Prospect i ve direct comparison of paired measurements by both techniques in each patient . Setting —Intensive care unit in a cardiovascular centre . Patients —65 patients after open heart surgery ( mean ( SD ) age 53 ( 12 ) years ) . Interventions —Cardiac output was measured simultaneously by the transoesophageal Doppler and thermodilution techniques . Cardiac output was measured again after a mechanical intervention or volume loading . Results —The limits of agreement were −2·53 to + 0·83 1·min−1 for cardiac output measured by the Doppler and thermodilution techniques . This suggests that the Doppler method alone would not be suitable for clinical use . The second measurement of cardiac output by thermodilution was compared with cardiac output estimated from the first and second Doppler measurements and the first thermodilution measurement . The limits of agreement ( −0·55 to + 0·51 1·min−1 ) were good enough for clinical use . Conclusions —After cardiac output had been measured simultaneously by both the Doppler and thermodilution techniques , subsequent transoesophageal Doppler alone gave a clinical ly useful measurement of cardiac output OBJECTIVE To compare the haemodynamic measurements of cardiac output ( CO ) , central venous pressure ( CVP ) , pulmonary capillary wedge pressure ( Pw ) and pulmonary artery systolic pressure ( PASP ) , obtained by Swan-Ganz catheter and transthoracic echocardiography . MATERIAL AND METHODS Prospect i ve study in a Medical/Surgical Intensive Care Unit ( ICU ) . A total of 41 post liver transplant patients were enrolled . CO , CVP , Pw and PASP , were simultaneously determined by two independent observers , utilizing a Swan-Ganz catheter and transthoracic echocardiography , using equations described in the literature . A linear correlation and a Bl and -Altman analysis were performed . RESULTS A good correlation between invasive and non- invasive measurements for CO ( r=0.97 ) and CVP ( r=0.88 ) was found , but determinations of Pw ( r=0.41 ) and PASP ( r=0.18 ) did not correlate well . Bias and 95 % confidence interval for CO were negligible namely when a CO<6 l/min was considered . Pulsed-wave Doppler-echocardiography underestimates the CO when compared with thermodilution , but the 2 techniques agree on average and can be used interchangeably . CONCLUSIONS The non-invasive determination of CO in critical care post liver transplant patients correlates well with the invasive determinations . Transthoracic echocardiography was not appropriate for calculating filling parameters studied . Although the data was obtained in post liver transplant patients , they could be useful in defining the role of echocardiography in the ICU Background and objective : Intraoperative Doppler ultrasound can be used to measure cardiac output by transoesophageal echocardiography . Recently , its reliability , when compared to the thermodilution technique , has been question ed . The purpose of this study was to compare intraoperative changes in cardiac output measured by echo‐Doppler and by thermodilution in cardiac surgery . We also assessed the agreement between the techniques . Methods : Fifty cardiac surgical patients ( 38 male , 12 female , mean age of 63.4 ± 14.3 yr ) were prospect ively included after approval by the Ethics Committee of the Institution . Cardiac output was assessed by thermodilution , with 10 mL saline at 12 ° C , and simultaneously and blindly by echo‐Doppler in deep transgastric view with pulsed wave Doppler at the level of the left ventricular outflow tract . Matched thermodilution cardiac output and echo‐Doppler cardiac output measurements were taken three times at the end of expiration , both pre‐ and post‐cardiopulmonary bypass . Results : Echo‐Doppler measurements were obtained in 44 patients ( 88 % ) . In three patients , Doppler recordings could not be obtained adequately , and three developed left ventricular outflow tract obstruction after bypass . Bl and ‐Altman analysis revealed a bias of 0.015 L min−1 , with narrow limits of agreement ( −1.21 to 1.22 L min−1 ) and 29.1 % error . Echo‐Doppler was accurate ( 92 % sensitivity and 71 % specificity , P = 0.008 by receiver operating characteristic curves ) for detecting more than 10 % of change in thermodilution cardiac output . There were no complications related to the study . Conclusions : The agreement between cardiac output by echo‐Doppler and by thermodilution is clinical ly acceptable and transoesophageal echocardiography is a reliable tool to assess significant cardiac output changes in a population of selected patients OBJECTIVE To compare cardiac output ( CO ) , stroke volume ( SV ) , and cardiac index ( CI ) as estimated with a new , noninvasive Doppler device ( Ultrasonic Cardiac Output Monitor [ USCOM ] ; USCOM Ltd , Sydney , Australia ) with those measured with the bolus thermodilution ( TD ) technique . DESIGN Prospect i ve nonr and omized study . SETTING Postcardiac surgery recovery unit of a tertiary cardiac center . PARTICIPANTS Fifty patients after off-pump coronary artery bypass ( OPCAB ) surgery . MEASUREMENT AND MAIN RESULTS Both right-sided and left-sided CO were estimated with a USCOM continuous-wave ( CW ) Doppler device , and CO was determined with the bolus TD technique performed in triplicate . On comparing the right-sided CO , SV , and CI with those of TD , the mean bias was 0.03 L/min , 1.6 mL , and 0.02 L/min/m(2 ) , respectively . The comparison of left-sided CO , SV , and CI with those of TD revealed a means bias of 0.14 L/min , 1.0 mL , and 0.08 L/min/m(2 ) , respectively . CONCLUSION This study showed excellent agreement between the values for CO , SV , and CI as determined with USCOM and TD . Since there was only 1 time period for CO estimation in each patient with both methods , the stability of this correlation needs to be further investigated over time Background : The use of transesophageal echocardiography for the determination of cardiac output ( CO ) has been limited to date . We assessed the capability of aortic continuous-wave Doppler transesophageal echocardiography to determine CO ( DCO ) in a transgastric long-axis imaging plane of the heart by comparing DCO to thermodilution CO ( TCO ) . Methods : DCO was determined in 63 consecutive patients undergoing cardiac surgery . Aortic valve area was obtained from the transverse short-axis view of the valve assuming a triangular shape for the valve orifice . Stroke volume was calculated as the product of velocity – time integral and aortic valve area : stroke volume = velocity – time integral × aortic valve area . DCO was calculated off-line , by multiplying stroke volume with heart rate : DCO = stroke volume × heart rate . Results : The aortic valve orifice was easily imaged in all patients . Excellent- quality continuous-wave Doppler flow profiles were obtained in nearly all ( 62 of 63 ) . A total of 109 DCO determinations were performed . Mean DCO was 4.35 ± 1.18 1·min-1 ( range 2.02 - 7.42 1·min-1 ) , and mean TCO was 4.41 ± 1.17 1·min-1 ( range 2.24 - 8.94 1·min-1 ) . Very high correlation and agreement were found between the two methods : DCO = 0.94 × TCO + 0.19 , r=0.94 , SEE ( st and ard error of the estimate ) = 0.41 1·min-1 ; 95 % confidence interval=0.06 ± 0.83 1·min-1 . Relative changes from pre- to postbypass CO ( Δ ) also showed a strong correlation ( ΔDCO=0.93 × ΔTCO + 5.4 % , r=0.82 , SEE=17.8 % ) . For CO changes greater than 10 % , Doppler was in accordance with thermodilution in 43 of 45 measurements . DCO repeatability coefficient was 0.51 1·min-1 . Conclusions : Compared to thermodilution , continuous-wave Doppler measurements of blood flow velocity across the aortic valve in the transesophageal echocardiographic transgastric view allow accurate CO determination Objective To compare the assessment of cardiac output ( CO ) in children using the noninvasive Ultrasound Cardiac Output Monitor ( USCOM ) with the invasive pulmonary artery catheter ( PAC ) thermodilution cardiac output measurement . Design and setting Prospect i ve observational study in a tertiary center for pediatric cardiology of a university children 's hospital . Patients Twenty-four pediatric patients with congenital heart disease without shunt undergoing cardiac catheterization under general anesthesia . Measurements and results CO was measured by USCOM using a suprasternal CO Doppler probe in children undergoing cardiac catheterization . USCOM data were compared to CO simultaneously measured by PAC thermodilution technique . Measurements were repeated three times within 5 min in each patient . A mean percentage error not exceeding 30 % was defined as indicating clinical useful reliability of the USCOM . CO values measured by PAC ranged from 1.3 to 5.3 l/min ( median 3.6 l/min ) . Bias and precision were −0.13 and 1.34 l/min , respectively . The mean percentage error of CO measurement by the USCOM compared to PAC thermodilution technique was 36.4 % for USCOM . Conclusions Our preliminary data demonstrate that cardiac output measurement in children using the USCOM does not reliably represent absolute CO values as compared to PAC thermodilution . Further studies must evaluate the impact of incorporating effective aortic valve diameters on CO measurement using the USCOM BACKGROUND The USCOM ultrasonic cardiac output monitor ( USCOM Pty Ltd , Coffs Harbour , NSW , Australia ) is a non-invasive device that determines cardiac output by continuous-wave Doppler ultrasound . The aim of this study was to evaluate the accuracy of the USCOM device compared with the thermodilution technique in intensive care patients who had just undergone cardiac surgery . METHODS We conducted a prospect i ve study in the 18-bed intensive care unit of a 600-bed tertiary referral hospital . Twenty-four mechanically ventilated patients were studied immediately following cardiac surgery . We evaluated the USCOM monitor by comparing its output with paired measurements obtained by the st and ard thermodilution technique using a pulmonary artery catheter . RESULTS Forty paired measurements were obtained in 22 patients . We were unable to obtain an acceptable signal in the remaining two patients . Comparison of the two techniques showed a bias of 0.18 and limits of agreement of -1.43 to 1.78 . The agreement may not be as good between techniques at higher cardiac output values . CONCLUSIONS The USCOM monitor has a place in intensive care monitoring . It is accurate , rapid , safe , well-tolerated , non-invasive and cost-effective . The learning curve for skill acquisition is very short . However , during the learning phase the USCOM monitor measurements are rather ' operator dependent ' . Its suitability for use in high and low cardiac output states requires further validation The present study compares the cardiac output ( CO ) estimated by a new , non-invsive continuous Doppler device ( Ultrasonic cardiac output monitor-USCOM ) with that by bolus thermodilution technique ( TD ) . Thirty post off-pump coronary artery bypass graft surgery patients were studied in this prospect i ve nonr and omized study . Right heart CO estimation by USCOM and TD was performed and measured in quadruplet . A total of 120 paired observations were made . The mean CO was 4.63 and 4.76 Llmin as estimated by TD and USCOM respectively . For TD and USCOM , the CO had a mean bias ( tendency of one technique to differ from other ) of -0.13 L/min and limits of agreement ( mean bias + /- 2SD ) at -0.86 and 0.59 L/min . The study reveals very good agreement between the values of CO estimated by USCOM and TD USCOM is an ultrasound-based method which has been accepted for noninvasive hemodynamic monitoring in various clinical conditions ( USCOM , Ultrasonic cardiac output monitoring ) . The present study aim ed at comparing the accuracy of the USCOM device with that of the thermodilution technique in patients with septicemia . We conducted a prospect i ve observational study in a medical but noncardiological ICU of a university hospital . Septic adult patients ( median age 55 years , median SAPS-II-Score 43 points ) on mechanical ventilation and catecholamine support were monitored with USCOM and PiCCO ( n = 70 ) . Seventy paired left-sided CO measurements ( transaortic access = COUS-A ) were obtained . The mean COUS-A were 6.55 l/min ( ±2.19 ) versus COPiCCO 6.5 l/min ( ±2.18 ) . The correlation coefficient was r = 0.89 . Comparison by Bl and -Altman analysis revealed a bias of −0.36 l/min ( ±0.99 l/min ) leading to a mean percentage error of 29 % . USCOM is a feasible and rapid method to evaluate CO in septic patients . USCOM does reliably represent CO values as compared to the reference technique based on thermodilution ( PiCCO ) . It seems to be appropriate in situations where CO measurements are most pertinent to patient management Sixteen obstetric patients Output:	Although the difference in CO between echocardiography by different types or sites and TD was not entirely consistent , the overall effect of meta- analysis showed that no significant differences were observed between US and TD . The techniques may be interchangeable under certain conditions
MS22163	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The aim of this study was to investigate the effects of very high intensity sprint interval training ( SIT ) on metabolic and vascular risk factors in overweight/obese sedentary men . Ten men ( age , 32.1 ± 8.7 years ; body mass index , 31.0 ± 3.7 kg m(-2 ) ) participated . After baseline metabolic , anthropometric , and fitness measurements , participants completed a 2-week SIT intervention , comprising 6 sessions of 4 to 6 repeats of 30-second Wingate anaerobic sprints on an electromagnetically braked cycle ergometer , with 4.5-minute recovery between each repetition . Metabolic , anthropometric , and fitness assessment s were repeated post-intervention . Both maximal oxygen uptake ( 2.98 ± 0.15 vs 3.23 ± 0.14 L min(-1 ) , P = .013 ) and mean Wingate power ( 579 ± 24 vs 600 ± 19 W , P = .040 ) significantly increased after 2 weeks of SIT . Insulin sensitivity index ( 5.35 ± 0.72 vs 4.34 ± 0.72 , P = .027 ) and resting fat oxidation rate in the fasted state ( 0.13 ± 0.01 vs 0.11 ± 0.01 g min(-1 ) , P = .019 ) were significantly higher and systolic blood pressure ( 121 ± 3 vs 127 ± 3 mm Hg , P = .020 ) and resting carbohydrate oxidation in the fasted state ( 0.03 ± 0.01 vs 0.08 ± 0.02 g min(-1 ) , P = .037 ) were significantly lower 24 hours post-intervention compared with baseline , but these changes were no longer significant 72 hours post-intervention . Significant decreases in waist ( 98.9 ± 3.1 vs 101.3 ± 2.7 cm , P = .004 ) and hip ( 109.8 ± 2.2 vs 110.9 ± 2.2 cm , P = .017 ) circumferences compared with baseline were also observed after the intervention . Thus , 2 weeks of SIT substantially improved a number of metabolic and vascular risk factors in overweight/obese sedentary men , highlighting the potential for this to provide an alternative exercise model for the improvement of vascular and metabolic health in this population Low-volume sprint interval training ( SIT ) , or repeated sessions of brief , intense intermittent exercise , elicits metabolic adaptations that resemble traditional high-volume endurance training ( ET ) . The effects of these different forms of exercise training on vascular structure and function remain largely unexplored . To test the hypothesis that SIT and ET would similarly improve peripheral artery distensibility and endothelial function and central artery distensibility , we recruited 20 healthy untrained subjects ( age : 23.3 + /- 2.8 yr ) and had them perform 6 wk of SIT or ET ( n = 5 men and 5 women per group ) . The SIT group completed four to six 30-s " all-out " Wingate tests separated by 4.5 min of recovery 3 days/wk . The ET group completed 40 - 60 min of cycling at 65 % of their peak oxygen uptake ( Vo2peak ) 5 days/wk . Popliteal endothelial function , both relative and normalized to shear stimulus , was improved after training in both groups ( main effect for time , P < 0.05 ) . Carotid artery distensibility was not statistically altered by training ( P = 0.29 ) in either group ; however , popliteal artery distensibility was improved in both groups to the same degree ( main effect , P < 0.05 ) . We conclude that SIT is a time-efficient strategy to elicit improvements in peripheral vascular structure and function that are comparable to ET . However , alterations in central artery distensibility may require a longer training stimuli and /or greater initial vascular stiffness than observed in this group of healthy subjects Our purpose was to examine the effects of sprint interval training on muscle glycolytic and oxidative enzyme activity and exercise performance . Twelve healthy men ( 22 + /- 2 yr of age ) underwent intense interval training on a cycle ergometer for 7 wk . Training consisted of 30-s maximum sprint efforts ( Wingate protocol ) interspersed by 2 - 4 min of recovery , performed three times per week . The program began with four intervals with 4 min of recovery per session in week 1 and progressed to 10 intervals with 2.5 min of recovery per session by week 7 . Peak power output and total work over repeated maximal 30-s efforts and maximal oxygen consumption ( VO2 max ) were measured before and after the training program . Needle biopsies were taken from vastus lateralis of nine subjects before and after the program and assayed for the maximal activity of hexokinase , total glycogen phosphorylase , phosphofructokinase , lactate dehydrogenase , citrate synthase , succinate dehydrogenase , malate dehydrogenase , and 3-hydroxyacyl-CoA dehydrogenase . The training program result ed in significant increases in peak power output , total work over 30 s , and VO2 max . Maximal enzyme activity of hexokinase , phosphofructokinase , citrate synthase , succinate dehydrogenase , and malate dehydrogenase was also significantly ( P < 0.05 ) higher after training . It was concluded that relatively brief but intense sprint training can result in an increase in both glycolytic and oxidative enzyme activity , maximum short-term power output , and VO2 max Adaptations in fat and carbohydrates metabolism after a prolonged endurance training program were examined using stable isotope tracers of glucose ( [6,6 - 2H2]glucose ) , glycerol ( [2H5]glycerol ) , and palmitate ( [2H2]palmitate ) . Active , but untrained , males exercised on a cycle for 2 h/day [ 60 % pretraining peak O2 consumption ( VO2peak ) = 44.3 + /- 2.4 ml.kg-1.min-1 ] for a total of 31 days . Three cycle tests ( 90 min at 60 % pretraining VO2peak ) were administered before training ( PRE ) and after 5 ( 5D ) and 31 ( 31D ) days of training . Exercise increased the rate of glucose production ( Ra ) and utilization ( Rd ) as well as the rate of lipolysis ( glycerol Ra ) and free fatty acid turnover ( FFARa/Rd ) . At 5D , training induced a 10 % ( P < 0.05 ) increase in total fat oxidation because of an increase in intramuscular triglyceride oxidation ( + 63 % , P < 0.05 ) and a decreased glycogen oxidation ( -16 % , P < 0.05 ) . At 31D , total fat oxidation during exercise increased a further 58 % ( P < 0.01 ) . The pattern of fat utilization during exercise at 31D showed a reduced reliance on plasma FFA oxidation ( FFA Rd ) and a greater dependence on oxidation of intramuscular triglyceride , which increased more than twofold ( P < 0.001 ) . In addition , glucose Ra and Rd were reduced at all time points during exercise at 31D compared with PRE and 5D . We conclude that long-term training induces a progressive increase in fat utilization mediated by a greater oxidation of fats from intramuscular sources and a reduction in glucose oxidation . Initial changes are present as early as 5D and occur before increases in muscle maximal mitochondrial enzyme activity UNLABELLED Repeated maximal-intensity short- duration exercise ( sprint interval training , SIT ) can produce muscle adaptations similar to endurance training ( ET ) despite a much reduced training volume . However , most SIT data use cycling , and little is known about its effects on body composition or maximal cardiac output ( Qmax ) . PURPOSE The purpose of this study was to assess body composition , 2000-m run time trial , VO(2max ) , and Q(max ) effects of run SIT versus ET . METHODS Men and women ( n = 10 per group ; mean ± SD : age = 24 ± 3 yr ) trained three times per week for 6 wk with SIT , 30-s all-out run sprints ( manually driven treadmill ) , four to six bouts per session , 4-min recovery per bout , versus ET , 65 % VO(2max ) for 30 to 60 min·d(-1 ) . RESULTS Training improved ( P < 0.05 ) body composition , 2000-m run time trial performance , and VO(2max ) in both groups . Fat mass decreased 12.4 % with SIT ( mean ± SEM ; 13.7 ± 1.6 to 12.0 ± 1.6 kg ) and 5.8 % with ET ( 13.9 ± 1.7 to 13.1 ± 1.6 kg ) . Lean mass increased 1 % in both groups . Time trial performance improved 4.6 % with SIT ( -25.6 ± 8.1 s ) and 5.9 % with ET ( -31.9 ± 6.3 s ) . VO(2max ) increased 11.5 % with SIT ( 46.8 ± 1.6 to 52.2 ± 2.0 mL·kg·(-1)·min(-1 ) ) and 12.5 % with ET ( 44.0 ± 2.0 to 49.5 ± 2.6 mL·kg·(-1)·min(-1 ) ) . None of these improvements differed between groups . In contrast , Q(max ) increased by 9.5 % with ET only ( 22.2 ± 2.0 to 24.3 ± 1.6 L·min(-1 ) ) . CONCLUSIONS Despite a fraction of the time commitment , run SIT induces similar body composition , VO(2max ) , and performance adaptations as ET , but with no effect on Q(max ) . These data suggest that adaptations with ET are of central origin primarily , whereas those with SIT are more Parra et al. ( Acta Physiol . Sc and 169 : 157 - 165 , 2000 ) showed that 2 wk of daily sprint interval training ( SIT ) increased citrate synthase ( CS ) maximal activity but did not change " anaerobic " work capacity , possibly because of chronic fatigue induced by daily training . The effect of fewer SIT sessions on muscle oxidative potential is unknown , and aside from changes in peak oxygen uptake ( Vo(2 peak ) ) , no study has examined the effect of SIT on " aerobic " exercise capacity . We tested the hypothesis that six sessions of SIT , performed over 2 wk with 1 - 2 days rest between sessions to promote recovery , would increase CS maximal activity and endurance capacity during cycling at approximately 80 % Vo(2 peak ) . Eight recreationally active subjects [ age = 22 + /- 1 yr ; Vo(2 peak ) = 45 + /- 3 ml.kg(-1).min(-1 ) ( mean + /- SE ) ] were studied before and 3 days after SIT . Each training session consisted of four to seven " all-out " 30-s Wingate tests with 4 min of recovery . After SIT , CS maximal activity increased by 38 % ( 5.5 + /- 1.0 vs. 4.0 + /- 0.7 mmol.kg protein(-1).h(-1 ) ) and resting muscle glycogen content increased by 26 % ( 614 + /- 39 vs. 489 + /- 57 mmol/kg dry wt ) ( both P < 0.05 ) . Most strikingly , cycle endurance capacity increased by 100 % after SIT ( 51 + /- 11 vs. 26 + /- 5 min ; P < 0.05 ) , despite no change in Vo(2 peak ) . The coefficient of variation for the cycle test was 12.0 % , and a control group ( n = 8) showed no change in performance when tested approximately 2 wk apart without SIT . We conclude that short sprint interval training ( approximately 15 min of intense exercise over 2 wk ) increased muscle oxidative potential and doubled endurance capacity during intense aerobic cycling in recreationally active individuals The insulin resistance of skeletal muscle in glucose-tolerant obese individuals is associated with reduced activity of oxidative enzymes and a disproportionate increase in activity of glycolytic enzymes . Because non-insulin-dependent diabetes mellitus ( NIDDM ) is a disorder characterized by even more severe insulin resistance of skeletal muscle and because many individuals with NIDDM are obese , the present study was undertaken to examine whether decreased oxidative and increased glycolytic enzyme activities are also present in NIDDM . Percutaneous biopsy of vatus lateralis muscle was obtained in eight lean ( L ) and eight obese ( O ) nondiabetic subjects and in eight obese NIDDM subjects and was assayed for marker enzymes of the glycolytic [ phosphofructokinase , glyceraldehyde phosphate dehydrogenase , hexokinase ( HK ) ] and oxidative pathways [ citrate synthase ( CS ) , cytochrome-c oxidase ] , as well as for a gly Output:	Strong evidence support improvements of aerobic exercise performance and VO2max following SIT . Solid evidence support peripheral adaptations known to increase the oxidative potential of the muscle following SIT , whereas evidence regarding central adaptations was limited and equivocal . Some evidence indicated changes in substrate oxidation at rest and during exercise as well as improved glycemic control and insulin sensitivity following SIT . In conclusion , strong evidence support improvement of aerobic exercise performance and VO2max following SIT , which coincides with peripheral muscular adaptations .
MS22164	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE The authors examined which , if any , research design features and patient characteristics would significantly differ between successful and unsuccessful antidepressant trials . METHOD Clinical trial data were review ed for nine antidepressants approved by the Food and Drug Administration between 1985 and 2000 . From the antidepressant research programs on these medications , 52 clinical trials were included in the study . The authors evaluated trial design features , patient characteristics , and difference in response between placebo and antidepressant . RESULTS Nine trial design features and patient characteristics were present in the research programs for all nine of the antidepressants . The severity of depressive symptoms before patient r and omization , the dosing schedule ( flexible versus fixed ) , the number of treatment arms , and the percentage of female patients were significantly associated with the difference in response to antidepressant and placebo . The duration of the antidepressant trial , number of patients per treatment arm , number of sites , and mean age of the patients were similar in successful trials ( with a greater antidepressant-placebo difference ) and less successful trials ( with a smaller antidepressant-placebo difference ) . CONCLUSIONS These findings may help in the design of future antidepressant trials Pharmacotherapy and psychotherapy are generally effective treatments for major depressive disorder ( MDD ) ; however , research suggests that patient preferences may influence outcomes . We examined the effects of treatment preference on attrition , therapeutic alliance , and change in depressive severity in a longitudinal r and omized clinical trial comparing pharmacotherapy and psychotherapy . Prior to r and omization , 106 individuals with MDD reported whether they preferred psychotherapy , antidepressant medication , or had no preference . A mismatch between preferred and actual treatment was associated with greater likelihood of attrition , fewer expected visits attended , and a less positive working alliance at session 2 . There was a significant indirect effect of preference match on depression outcomes , primarily via effects of attendance . These findings highlight the importance of addressing patient preferences , particularly in regard to patient engagement , in the treatment of MDD OBJECTIVE The authors examined the association of treatment preferences with treatment initiation , adherence , and clinical outcome among nonsenior adult and senior primary care patients with depression . METHODS Sixty primary care participants meeting DSM-IV criteria for major depression were r and omly assigned to receive treatment congruent or incongruent with their primary stated preference . Participants received either 20 weeks of escitalopram , with monitoring by a care manager , or 12 weekly sessions of interpersonal psychotherapy followed by two monthly booster sessions . Adherence to treatment and depression severity were reassessed at weeks 4 , 8 , 12 , and 24 . RESULTS Participants expressed stronger preferences for psychotherapy than for antidepressant medication . Preference strength was a more sensitive measure of outcome than was congruence versus incongruence of preference with the assigned treatment . Across age groups , preference strength was significantly associated with treatment initiation and 12-week adherence rate but not with depression severity or remission . CONCLUSIONS A continuous measure of preference strength may be a more useful measure in clinical practice than preferences per se . Future research should focus on whether and how greater facilitation of the treatment decision-making process between patient and clinician influences clinical outcome Rejection of catheters is generally thought to be due to patients pulling out their catheters , but we found circumstantial evidence for this in only one third of cases . Some catheters with smaller balloons drop out spontaneously , perhaps owing to laxity of the pelvic floor or urethral dilatation caused by repeated catheterisation , and others are expelled forcibly , presumably owing to uninhibited contractions of the bladder . Urinary catheters may therefore drop out , be pushed out , or be pulled out . The life expectancy of catheters in this group of patients suggests the type of catheter that should be used . We recommend cheaper latex catheters and think that expensive " long life " silicon catheters are inappropriate in most long stay patients . Rejection of catheters is common in poorly mobile old people with cognitive impairment . It is associated with urethral trauma and may result in septicaemia . Long term catheterisation should therefore be considered only when other methods to promote continence and provide comfort have failed.3 Further work is needed to determine why some patients pull out their catheters and whether bladder stabilising drugs might reduce episodes of spontaneous rejection of catheters Background : Clinicians and research ers have question ed whether participants in r and omized control trials ( RCTs ) are representative of patients in the broader clinical population . Method : We compared the demographic , clinical , and personality characteristics of patients ( N=256 ) with major depressive disorder ( MDD ) receiving antidepressant medication or interpersonal therapy as part of an RCT investigation ( n=105 ) versus in a clinic ( n=151 ) . The RCT and clinic protocol s were identical with the exception of recruitment procedures ( advertisement versus physician referral ) and assignment to treatment ( r and omized versus nonr and omized ) . Results : No significant differences emerged between the RCT participants and clinic patients for sex , age , marital status , and education . Overall , clinic patients were no more severely depressed compared to RCT participants ; there was , however , a significant interaction effect . Response rates were significantly higher for RCT participants versus clinic patients . Those participating in the RCT scored significantly higher on a personality scale assessing preference for novel experiences compared to those in the clinic . Conclusions : Differences in clinical and personality variables between those receiving treatment for MDD as part of an RCT versus in a clinic exist ; however , the clinical significance of these differences remains in question , as these variables were unrelated to treatment outcome . Depression and Anxiety , 2009 . © 2009 Wiley‐Liss , A new wave of meta-analyses suggests that antidepressants are no better than placebo for major depressive disorder ( MDD ) , and therefore , antidepressants not only do n't work , but even worse , they harm patients because of the risk of adverse effects . The authors analyzed data from all antidepressant studies su bmi tted to the Food and Drug Administration for registration ( including failed studies with inordinately high placebo reponses ) , or used a met analysis filter and selected those few studies that meet those criteria . In aggregate , the data , at best , show a clinical ly trivial advantage of the antidepressants over placebo in acute r and omized trials . However , their conclusions range from antidepressants do n't work at all to the antidepressants should be reserved only for the most seriously depressed patients . Kirsch is capitalizing on this trend with his recently published book . I view this debate through my perspective of over 25 years of clinical experience , serving as a rater for clinical trials , planning and conducting National Institute of Mental Health and industry efficacy and effectiveness clinical trials , and consulting to the pharmaceutical industry . The real story , I believe , is a bit more complicated . Give everyone with fever penicillin and many will improve . Compare penicillin to placebo and on average , you would find no difference . Why ? Most people with fever have viral infections or non-penicillin sensitive bacterial infections that are time limited ( eg , common upper respiratory infections ) . One could reasonably conclude that penicillin does n't work and we should all take chicken soup instead . Give everyone with MDD an antidepressant and many will improve . Compare any given antidepressant to placebo and on average , you should find no difference . Yet , a difference does exist and even if the trials have an overall small effect size in favor of antidepressants , it is not quite accurate to state that antidepressants are equal to placebo . Why ? If that were true , then in a third of the trials placebo would beat antidepressants , in a third of the trials antidepressants would beat placebo , and the remaining third of the trials it would be a tie . MDD is analogous to fever . It is a heterogeneous , nonspecific syndrome that is the final common pathway of multiple dysregulated psychological and brain processes . Genetic epidemiological studies strongly suggest that stress is a causal factor and that the persistence or The assumption that depressed patients who are assigned to placebo in antidepressant clinical trials are exposed to substantial morbidity and mortality has not been based on research data . Because of worldwide concern about placebo use and the implication s of our earlier findings of no increased suicide risk in placebo-treated patients , we conducted a replication study in a new patient sample . We assessed suicide risk and symptom reduction among placebo-treated patients participating in antidepressant clinical trials for two recently approved antidepressants , venlafaxine ER and citalopram , which were unavailable during our previous study . Among 23,201 participant patients , 32 committed suicide and 172 attempted suicide . Rates of suicide and attempted suicide did not differ significantly among the placebo- and drug-treated groups . Based on patient exposure years , annual rates of suicide and attempted suicide were 0.5 and 6.7 % with placebo , 0.9 % with active comparator ( rates for attempted suicide are unavailable ) , and 0.6 and 6.3 % with investigational antidepressants . Symptom reduction was 47.9 % with investigational drugs ( n = 1172 ) , 47.5 % with active comparators ( n = 161 ) , and 35.5 % with placebo ( n = 606 ) . These data may inform discussion s about the use of placebo in antidepressant clinical trials Output:	Differences were not seen with psychotherapy compared to antidepressants , alternative therapies or active intervention controls . CONCLUSIONS In conclusion , the combination of psychotherapy and antidepressants for depression may provide a slight advantage whereas antidepressants alone and psychotherapy alone are not significantly different from alternative therapies or active intervention controls . These data suggest that type of treatment offered is less important than getting depressed patients involved in an active therapeutic program .
MS22165	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Patients with first-episode schizophrenia appear to respond to lower doses of neuroleptics , and to be more sensitive to developing extrapyramidal side-effects . The authors therefore compared in such patients the efficacy and extrapyramidal tolerability of comparatively low dosages of the atypical neuroleptic risperidone and of the conventional neuroleptic haloperidol . Risperidone was hypothesized to have better extrapyramidal tolerability and efficacy in treating negative symptoms . Patients were r and omly assigned under double-blind conditions to receive risperidone ( n=143 ) or haloperidol ( n=146 ) for 8 wk . The primary efficacy criterion was the estimated difference in the mean change in the Positive and Negative Symptom Scale ( PANSS ) negative score between treatment groups ; secondary efficacy criteria were changes on the PANSS total score and other PANSS subscores , and several other measures of psychopathology and general functioning . The primary tolerability criterion was the difference in baseline-adjusted occurrence rates of extrapyramidal side-effects measured with the Simpson-Angus Scale ( SAS ) compared between treatment groups . The main hypothesis was that risperidone would be superior in terms of improving negative symptoms and lowering the risk of extrapyramidal symptoms . Secondary tolerability criteria were the other extrapyramidal symptoms , measured with the Hillside Akathisia Scale ( HAS ) and the Abnormal Involuntary Movement Scale ( AIMS ) . The average mean daily doses were 3.8 mg ( s.d.=1.5 ) for risperidone and 3.7 mg ( s.d.=1.5 ) for haloperidol . There were similar , significant improvements in both treatment groups in the primary and secondary efficacy criteria . At week 8 nearly all scores of extrapyramidal side-effects indicated a significantly higher prevalence of extrapyramidal side-effects with haloperidol than with risperidone [ SAS : risperidone 36.5 % of patients ; haloperidol 51.5 % of patients ; likelihood ratio test , chi2(1)=7.8 , p=0.005 ] . There were significantly fewer drop-outs [ risperidone n=55 , drop-out rate=38.5 % ; haloperidol n=79 , drop-out rate=54.1 % , chi2(1)=7.1 , p=0.009 ] and a longer non-discontinuation time [ risperidone : average of 50.8 d to drop-out ; haloperidol : average of 44.0 d to drop-out ; log rank test , chi2(1)=6.4 , p=0.011 ] in the risperidone group . Risperidone and haloperidol appear to be equally effective in treating negative and other symptoms of first-episode schizophrenia . Risperidone has better extrapyramidal tolerability and treatment retention rate than the equivalent dose of haloperidol in these patients Abstract .In first-episode schizophrenia the advantage of new atypical neuroleptics compared to low-dose haloperidol as well as the indicated duration of neuroleptic maintenance treatment has still to be based on empirical evidence .Accordingly , a multi-center study on the optimization of acute and long-term treatment in first-episode schizophrenia is currently being carried out as part of the German Research Network on Schizophrenia . This paper reports on the design , methods and preliminary results of the two-year r and omized double-blind study comparing risperidone and low-dose haloperidol within the framework of psychological interventions . In the second treatment year , relapse rates under continued neuroleptic treatment are compared with those under stepwise drug withdrawal substituting instead prodrome-based early intervention ( intermittent treatment).As to the results , by November 2003 142 first episode patients ( ICD-10 F20 ) have been included in the long-term study . One-year relapse rates were very low ( 3.8 % ) . On average , symptoms as well as drug side-effects decreased steadily under maintenance treatment . Although compliance on average was high , about 60 % of the patients dropped out during the first study year . More pronounced psychopathology , ( neurological ) side-effects , lower compliance at study entry and absence of psychological treatment seemed to enhance the risk for drop-out . In conclusion , treatment in first episode schizophrenia is effective under both ( further on blinded ) neuroleptics ; however these patients are at high risk for treatment drop-out . This emphasizes the need for a special support program Background The true dose effect in flexible-dose clinical trials may be obscured and even reversed because dose and outcome are related . Methods To evaluate dose effect in response on primary efficacy scales from 2 r and omized , double-blind , flexible-dose trials of patients with bipolar mania who received olanzapine ( N = 234 , 5–20 mg/day ) , or patients with schizophrenia who received olanzapine ( N = 172 , 10–20 mg/day ) , we used marginal structural models , inverse probability of treatment weighting ( MSM , IPTW ) methodology . Dose profiles for mean changes from baseline were evaluated using weighted MSM with a repeated measures model . To adjust for selection bias due to non-r and om dose assignment and dropouts , patient-specific time-dependent weights were determined as products of ( i ) stable weights based on inverse probability of receiving the sequence of dose assignments that was actually received by a patient up to given time multiplied by ( ii ) stable weights based on inverse probability of patient remaining on treatment by that time . Results were compared with those by unweighted analyses . Results While the observed difference in efficacy scores for dose groups for the unweighted analysis strongly favored lower doses , the weighted analyses showed no strong dose effects and , in some cases , reversed the apparent " negative dose effect . " Conclusion While naïve comparison of groups by last or modal dose in a flexible-dose trial may result in severely biased efficacy analyses , the MSM with IPTW estimators approach may be a valuable method of removing these biases and evaluating potential dose effect , which may prove useful for planning confirmatory trials OBJECTIVE Despite the frequent use of the Positive and Negative Syndrome Scale ( PANSS ) for rating the symptoms of schizophrenia , the clinical meaning of its total score and of the cut-offs that are used to define treatment response ( e.g. at least 20 % or 50 % reduction of the baseline score ) are as yet unclear . We therefore compared the PANSS with simultaneous ratings of Clinical Global Impressions ( CGI ) . METHOD PANSS and CGI ratings at baseline ( n = 4091 ) , and after one , two , four and six weeks of treatment taken from a pooled data base of seven pivotal , multi-center antipsychotic drug trials on olanzapine or amisulpride in patients with exacerbations of schizophrenia were compared using equipercentile linking . RESULTS Being considered " mildly ill " according to the CGI approximately corresponded to a PANSS total score of 58 , " moderately ill " to a PANSS of 75 , " markedly ill " to a PANSS of 95 and severely ill to a PANSS of 116 . To be " minimally improved " according to the CGI score was associated with a mean percentage PANSS reduction of 19 % , 23 % , 26 % and 28 % at weeks 1 , 2 , 4 and 6 , respectively . The corresponding figures for a CGI rating " much improved " were 40 % , 45 % , 51 % and 53 % . CONCLUSIONS The results provide a better framework for underst and ing the clinical meaning of the PANSS total score in drug trials of schizophrenia patients with acute exacerbations . Such studies may ideally use at least a 50 % reduction from baseline cut-off to define response rather than lower thresholds . In treatment resistant population s , however , even a small improvement can be important , so that a 25 % cut-off might be appropriate A double-blind , placebo-controlled trial was carried out to determine the value of maintenance therapy with phenothiazines in a population of out patients who had recently recovered from an acute episode of schizophrenia . The drug was shown to be significantly more effective than the placebo in preventing relapse . The relationship of the trial patients to the population from which they were selected was defined in terms of clinical , historical , and social data . Maintenance therapy seems of little value in patients with a good prognosis and in the severely ill , but it is of value in the indeterminate group between these two extremes A study was conducted to investigate a novel approach to the prophylaxis of schizophrenic relapse . The treatment strategy comprised brief intermittent courses of neuroleptic agents begun as soon as non-psychotic symptoms believed to be early signs of relapse appeared . Fifty four stable , remitted out patients meeting the American Psychiatric Association 's DSM-III criteria for schizophrenia were r and omised double blind to receive brief intermittent treatment with either active or placebo depot neuroleptic injections . Only three patients given placebo injections and two controls were admitted to hospital during one year of follow up . Eight ( 30 % ) of the patients given placebo injections and only 2 ( 7 % ) of the controls , however , had a recurrence of schizophrenic symptoms . Patients given placebo injections experienced fewer extrapyramidal side effects and showed a trend towards a reduction in tardive dyskinesia . Dysphoric and neurotic symptoms were identified before eight out of 11 relapses , and these symptoms were more frequent in patients given placebo depot injections . These results suggest a viable but not necessarily better alternative to continuous oral or depot treatment for less ill , chronic , stabilised schizophrenics based on the early treatment of putative prodromal symptoms of relapse The authors report on the outcome of treatment of 116 out patients with chronic schizophrenia who were assigned to a 2-year , single-blind course of treatment with either targeted or continuous medication . These patients were not restricted to those who were good c and i date s for a medication reduction strategy . Continuous medication was superior to targeted medication in preventing decompensations and hospitalizations and in extent of employment at 2 years . Other measures of psychopathology and functioning at 1 and 2 years did not differentiate the two groups of patients . The targeted approach achieved a substantial reduction in total medication through a reduction in the number of days of medication administration In a double-blind trial , 34 male chronic schizophrenic day- patients or in- patients in a hostel ward continued on fluphenazine decanoate given mostly once fortnightly or were switched to pimozide , given on four days each week . Over nine months relapse rates were similar for both groups , and while fewer patients on pimozide were prescribed antiparkinsonian drugs one quarter developed buccolingual masticatory dyskinesia . Plasma pimozide levels suggested satisfactory drug compliance . Average plasma prolactin levels were within the normal rage for untreated men in one quarter of non-relapsing patients on pimozide and three quarters on fluphenazine Summary Schizophrenic out patients ( = 364 ) were assigned at r and om to three different treatment strategies : ( 1 ) continuous medication with neuroleptic drugs , ( 2 ) intermittent medication with crisis intervention and ( 3 ) intermittent medication with early intervention . Depressive syndromes were rated according to three different scales for depressive syndromes ( Brief Psychiatric Rating Scale anxious depression factor , Arbeitsgemeinschaft für Method ik und Dokumentation in der Psychiatrie/depression , and the self-rating Paranoid Depression Scale ) after 1 and 2 years of treatment . No differences in depression scores were found between the three treatment strategies . Comparisons between patients treated with neuroleptic drugs at the time and patients without neuroleptics revealed significantly higher depression scores in the neuroleptics group in most comparisons . No differences were found between patients treated with low versus high potency neuroleptics and between oral versus depot neuroleptics . However , depression correlated with extrapyramidal symptoms The authors estimated components of variance and intraclass correlation coefficients ( ICCs ) to aid in the design of complex surveys and community intervention studies by analyzing data from the Health Survey for Engl and 1994 . This cross-sectional survey of English adults included data on a range of lifestyle risk factors and health outcomes . For the survey , households were sample d in 720 postal code sectors nested within 177 district health authorities and 14 regional health authorities . Study subjects were adults aged 16 years or more . ICCs and components of variance were estimated from a nested r and om-effects analysis of variance . Results are presented at the district health authority , postal code sector , and household levels . Between-cluster variation was evident at each level of clustering . In these data , ICCs were inversely related to cluster size , but design effects could be substantial when the cluster size was large . Most ICCs were below 0.01 at the district health authority level , and they were mostly below 0.05 at the postal code sector level . At the household level , many ICCs were in the range of 0.0 - 0.3 . These data may provide useful information for the design of epidemiologic studies in which the units sample d or allocated range in size from households to large administrative areas Results of studies on intermittent neuroleptic treatment strategies in first episode ( FE ) schizophrenia have not been published . Aims of the present study were to eluci date the comparative efficacy of prodrome-based neuroleptic intervention in first vs multiple episode ( ME ) schizophrenia . As to the methods , three r and omly assigned open neuroleptic treatment strategies were compared over 2 years in 363 schizophrenic out patients ( 115 FE , 248 ME ; ICD-9 , RDC ) : maintenance medication vs two intermittent medication strategies ( prodrome-based intervention and crisis intervention ) . Concerning relapse prevention , the results demonstrate that ME patients Output:	Results of this review support the existing evidence that intermittent antipsychotic treatment is not as effective as continuous , maintained antipsychotic therapy in preventing relapse in people with schizophrenia .
MS22166	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Little is known about the effects of successful psychotherapy on brain function in subjects with anxiety disorders . The present study aim ed to identify changes in brain activation following cognitive-behavioral therapy ( CBT ) in subjects suffering from specific phobia . Using functional magnetic resonance imaging ( fMRI ) , brain activation to spider videos was measured in 28 spider phobic and 14 healthy control subjects . Phobics were r and omly assigned to a therapy-group ( TG ) and a waiting-list control group ( WG ) . Both groups of phobics were scanned twice . Between scanning sessions , CBT was given to the TG . Before therapy , brain activation did not differ between both groups of phobics . As compared to control subjects , phobics showed greater responses to spider vs. control videos in the insula and anterior cingulate cortex ( ACC ) . CBT strongly reduced phobic symptoms in the TG while the WG remained behaviorally unchanged . In the second scanning session , a significant reduction of hyperactivity in the insula and ACC was found in the TG compared to the WG . These results propose that increased activation in the insula and ACC is associated with specific phobia , whereas an attenuation of these brain responses correlates with successful therapeutic intervention Neurofunctional mechanisms underlying cognitive behavior therapy ( CBT ) are still not clearly understood . This functional magnetic resonance imaging ( fMRI ) study focused on changes in brain activation as a result of one-session CBT in patients suffering from spider phobia . Twenty-six female spider phobics and 25 non-phobic subjects were presented with spider pictures , generally disgust-inducing , generally fear-inducing and affectively neutral scenes in an initial fMRI session . Afterwards , the patients were r and omly assigned to either a therapy group ( TG ) or a waiting list group ( WG ) . The scans were repeated one week after the treatment or after a one-week waiting period . Relative to the non-phobic participants , the patients displayed increased activation in the amygdala and the fusiform gyrus as well as decreased activation in the medial orbitofrontal cortex ( OFC ) during the first exposure . The therapy effect consisted of increased medial OFC activity in the TG relative to the WG . Further , therapy-related reductions in experienced somatic anxiety symptoms were positively correlated with activation decreases in the amygdala and the insula . We conclude that successful treatment of spider phobia is primarily accompanied by functional changes of the medial OFC . This brain region is crucial for the self-regulation of emotions and the relearning of stimulus-reinforcement associations BACKGROUND Neurofunctional changes underlying effective antianxiety treatments are incompletely characterized . This study explored the effects of citalopram and cognitive-behavioral therapy on regional cerebral blood flow ( rCBF ) in social phobia . METHODS By means of positron emission tomography with oxygen 15-labeled water , rCBF was assessed in 18 previously untreated patients with social phobia during an anxiogenic public speaking task . Patients were matched for sex , age , and phobia severity , based on social anxiety question naire data , and r and omized to citalopram medication , cognitive-behavioral group therapy , or a waiting-list control group . Scans were repeated after 9 weeks of treatment or waiting time . Outcome was assessed by subjective and psychophysiological state anxiety measures and self-report question naires . Questions were readministered after 1 year . RESULTS Symptoms improved significantly and roughly equally with citalopram and cognitive-behavioral therapy , whereas the waiting-list group remained unchanged . Four patients in each treated group and 1 waiting-list patient were classified as responders . Within both treated groups , and in responders regardless of treatment approach , improvement was accompanied by a decreased rCBF-response to public speaking bilaterally in the amygdala , hippocampus , and the periamygdaloid , rhinal , and parahippocampal cortices . Between-group comparisons confirmed that rCBF in these regions decreased significantly more in treated groups than control subjects , and in responders than nonresponders , particularly in the right hemisphere . The degree of amygdalar-limbic attenuation was associated with clinical improvement a year later . CONCLUSIONS Common sites of action for citalopram and cognitive-behavioral treatment of social anxiety were observed in the amygdala , hippocampus , and neighboring cortical areas , ie , brain regions subserving bodily defense reactions to threat BACKGROUND Functional brain imaging studies in major depression have suggested abnormalities of areas , including the frontal cortex , cingulate gyrus , basal ganglia , and temporal cortex . We hypothesized that venlafaxine hydrochloride and interpersonal psychotherapy ( IPT ) might each alter brain blood flow in some or all of these areas on sequential single photon emission computed tomography ( SPECT ) scans . METHODS Twenty-eight men and women aged 30 to 53 years with a DSM-IV major depressive episode , a 17-item Hamilton Rating Scale for Depression ( HAM-D ) rating of 18 or higher , and antidepressant-naive for at least 6 months were studied . After baseline (99m)technetium-hexa-methyl-propylene-amine-oxime scan , 1-T magnetic resonance imaging , and psychometric ratings , patients were assigned to different treatments . Thirteen patients had 1-hour weekly sessions of IPT from the same supervised therapist ( E.M. ) . Fifteen patients took 37.5 mg twice-daily of venlafaxine hydrochloride . Single-photon emission computed tomography scans and ratings were repeated at 6 weeks . RESULTS Both treatment groups improved substantially , more so with venlafaxine ( mean [ SD ] HAM-D scores at pretreatment : IPT , 22.7 [ 2.7 ] , and venlafaxine , 22.4 [ 3.1 ] ; and posttreatment : IPT , 16.2 [ 7.1 ] , and venlafaxine , 10.9 [ 8.6 ] ) . No patients had structural brain abnormalities . On analysis with statistical parametric mapping 96 , the venlafaxine group showed right posterior temporal and right basal ganglia activation ( P = .01 ) , while the IPT group had limbic right posterior cingulate and right basal ganglia activation ( P = .01 ) . CONCLUSIONS This preliminary investigation has shown limbic blood flow increase with IPT yet not venlafaxine , while both treatments demonstrated increased basal ganglia blood flow . This was , however , a short trial with a small sample , no control group , and different symptom reduction in the 2 groups BACKGROUND Magnetic resonance imaging ( MRI ) studies have especially reported smaller hippocampal volume in patients with post-traumatic stress disorder ( PTSD ) , most of them war or sexual abuse victims . The present study compares the hippocampal volumes of out- patients with PTSD who had low co-morbidity rates to those of trauma-exposed control subjects without PTSD , and measures hippocampal volume changes in these patients after brief eclectic psychotherapy . We hypothesized that smaller hippocampal volumes are specific to PTSD and that hippocampal volume changes after effective psychotherapy would be measurable . METHOD Eighteen patients with PTSD and 14 traumatized control subjects were examined with MRI . In a r and omized clinical trial , the PTSD patients were assigned to treatment ( n = 9 ) or waiting-list group ( n = 9 ) . After the former received psychotherapy for 4 months , the MRI was repeated on both PTSD groups . Three temporal lobe structures were manually segmented : hippocampus , amygdala , and parahippocampal gyrus . Volumetric analysis was used to measure grey matter , white matter , and cerebrospinal fluid . RESULTS PTSD patients had significantly smaller hippocampal volumes at baseline ( total 13.8 % , right 13.5 % , left 14.1 % ) compared to the control subjects . After effective psychotherapy , however , no volume changes were found in the smaller hippocampi . CONCLUSIONS We confirmed previous findings of smaller hippocampal volume in PTSD in a new population made up of out- patients who experienced different types of traumas , reducing co-morbidity to a minimum . Smaller hippocampal volumes did not change after effective psychotherapy , even while symptoms resolved Background Post-traumatic stress disorder ( PTSD ) is a derangement of mood control with involuntary , emotionally fraught re collection s that may follow deep psychological trauma in susceptible individuals . This condition is treated with pharmacological and /or cognitive therapies as well as psychotherapy with eye movement desensitization and reprocessing ( EMDR ) . However , only a very limited number of studies have been published dealing with work-related PTSD , and investigations on the effect of treatment on cerebral blood flow represent an even smaller number . Aim To investigate the short-term outcome of occupation-related PTSD after EMDR therapy by 99mTc-HMPAO SPECT . Method Fifteen patients , either train drivers suffering from PTSD after having been unintentionally responsible for a person-under-train accident or employees assaulted in the course of duty , were recruited for the study . 99mTc-HMPAO SPECT was performed on these patients both before and after EMDR therapy while they listened to a script portraying the traumatic event . Tracer distribution analysis was then carried out at volume of interest ( VOI ) level using a three-dimensional st and ardized brain atlas , and at voxel level by SPM . The CBF data of the 15 patients were compared before and after treatment as well as with those of a group of 27 controls who had been exposed to the same psychological traumas without developing PTSD . Results At VOI analysis significant CBF distribution differences were found between controls and patients before and after treatment ( P=0.023 and P=0.0039 , respectively ) . Eleven of the 15 patients responded to treatment , i.e. , following EMDR they no longer fulfilled the DSM-IV criteria for PTSD . When comparing only the eleven responders with the controls , the significant group difference found before EMDR ( P=0.019 ) disappeared after treatment . Responders and non-responders showed after therapy significant regional differences in frontal , parieto-occipital and visual cortex and in hippocampus . SPM analysis showed significant uptake differences between patients and controls in the orbitofrontal cortex ( Brodmann 11 ) and the temporal pole ( Brodmann 38 ) both before and after treatment . A significant tracer distribution difference present before treatment in the uncus ( Brodmann 36 ) disappeared after treatment , while a significant difference appeared in the lateral temporal lobe ( Brodmann 21 ) . ConclusionS ignificant 99mTc-HMPAO uptake regional differences were found , mainly in the peri-limbic cortex , between PTSD patients and controls exposed to trauma but not developing PTSD . Tracer uptake differences between responders and patients not responding to EMDR were found after treatment suggesting a trend towards normalization of tracer distribution after successful therapy . These findings in occupational related PTSD are consistent with previously described effects of psychotherapy on anxiety disorders Several neuroanatomical hypotheses of panic disorder have been proposed focusing on the significant role of the amygdala and PAG-related " panic neurocircuitry . " Although cognitive-behavioral therapy is effective in patients with panic disorder , its therapeutic mechanism of action in the brain remains unclear . The present study was performed to investigate regional brain glucose metabolic changes associated with successful completion of cognitive-behavioral therapy in panic disorder patients . The regional glucose utilization in patients with panic disorder was compared before and after cognitive-behavioral therapy using positron emission tomography with (18)F-fluorodeoxyglucose . In 11 of 12 patients who showed improvement after cognitive-behavioral therapy , decreased glucose utilization was detected in the right hippocampus , left anterior cingulate , left cerebellum , and pons , whereas increased glucose utilization was seen in the bilateral medial prefrontal cortices . Significant correlations were found between the percent change relative to the pretreatment value of glucose utilization in the left medial prefrontal cortex and those of anxiety and agoraphobia-related subscale of the Panic Disorder Severity Scale , and between that of the midbrain and that of the number of panic attacks during the 4 weeks before each scan in all 12 patients . The completion of successful cognitive-behavioral therapy involved not only reduction of the baseline hyperactivity in several brain areas but also adaptive metabolic changes of the bilateral medial prefrontal cortices in panic disorder patients BACKGROUND Functional brain-imaging studies in post-traumatic stress disorder ( PTSD ) have suggested functional alterations in temporal and prefrontal cortical regions . Effects of psychotherapy on these brain regions have not yet been examined . METHOD Twenty civilian PTSD out- patients and 15 traumatized control subjects were assessed at baseline using psychometric ratings . Cerebral blood flow was measured using trauma script-driven imagery during 99mtechnetium hexamethyl-propylene-amine-oxime single-photon emission computed tomography scanning . All 20 out- patients were r and omly assigned to treatment or wait-list conditions . Treatment was brief eclectic psychotherapy ( BEP ) in 16 weekly individual sessions . RESULTS At baseline , greater activation was found in the right insula and right superior/middle frontal gyrus in the PTSD group than in the control group . PTSD patients treated with BEP significantly improved on all PTSD symptom clusters compared to those on the waiting list . After effective psychotherapy , lower activation was measured in the right middle frontal gyrus , compared to the P Output:	Psychological interventions changed neural circuits involved in the pathophysiology of anxiety disorders , especially activity in frontal-striatal circuits in OCD and prefrontal areas in arachnophobia . Despite the variety of method ological concerns , initial neuroimaging studies have showed that psychological interventions can change brain function related to anxiety disorders in the patients who respond to treatment .
MS22167	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVES To show that hearing loss has such a high prevalence in the older population to justify screening , if effective and acceptable methods are available ; and that population take-up and benefit can make a measurable outcome difference in quality of life . DESIGN A population study of people aged 55 - 74 years was undertaken . A clinical effectiveness study of differently organised screening programmes was carried out using a controlled trial to identify those who might benefit from intervention ( and the extent of the benefit ) . A retrospective case-control study examined the very long-term ( more than 10 years ) compliance of patients in using their hearing aids after early identification and determined the extent to which early-identified hearing-impaired people have better outcomes than equivalent people identified later . An examination of the costs and cost-effectiveness of different potential screening programmes was also undertaken . SETTING A population study was design ed in the UK , with specific stages being conducted in more depth on a sample of people from Nottingham and Southampton . The clinical effectiveness study was conducted in general practice s in Nottingham and Bath using a systematic or opportunistic screen . The retrospective case-control study compared a group of early-identified hearing aid users , with control matched for age , gender and occupation , in Cardiff , Glasgow and Manchester . PARTICIPANTS In Great Britain responses were obtained for 34,362 individuals from the postal question naire as part of a population study , 506 were interviewed , 351 were assessed for benefit from amplification and 87 were fitted with a hearing aid . The clinical effectiveness study received 1461 replies from the first-stage question naire screen , with 306 people assessed in the clinic , of whom 156 were fitted with hearing aids . The retrospective case-control study traced 116 previously fitted hearing aid users , who had been identified by a screen , and then conducted a case-control using 50 of these for whom complete data were available , matching with two control groups of 50 people . INTERVENTIONS The major prospect i ve interventions were to introduce amplification through offering people , with minimal hearing impairment , hearing aid(s ) in a rehabilitative setting . In the population study , aids were offered as a monaural in-the-ear ( ITE ) hearing aid and in the clinical effectiveness study people who met the criteria were r and omised to be offered two different ITE hearing aids to be fitted bilaterally . The retrospective case-control study used unilateral and bilateral hearing aids . MAIN OUTCOME MEASURES Prevalence of hearing problems and degree to which services meet need in 55 - 74-year age group . Public acceptability and individual benefits of hearing screening and intervention as a function of demographic and hearing domain-specific characteristics . Improvement in quality of life . Screening costs and cost-effectiveness as a function of proposed programmes . RESULTS It was found that 12 % of people aged 55 - 74 years have a hearing problem that causes moderate or severe worry , annoyance or upset , 14 % have a bilateral hearing impairment of at least 35 dB hearing level ( HL ) and only 3 % currently receive intervention , through the use of hearing aids . Good amplification was shown to benefit about one in four of this 55 - 74-year-old population and the degree of hearing loss predicted benefit well . Overall , there was a strong correlation between benefit from amplification and from using hearing aids . Question naires and audiometric screens gave good screening operating characteristics . The systematic screening programme was more acceptable and gave a better response than the opportunistic . About 70 % of those who were offered an aid accepted a bilateral fitting . This increased to 95 % for those with > or = 35 dB HL ( averaged over 0.5 , 1 , 2 and 4 kHz in the better ear ) . The retrospective case-control study showed that long-term hearing aid use was low , unless hearing impairment was quite high ( e.g. > 35 dB HL ) . Those identified early had greater benefit through additional years of use/better adaptation to use than those of the same age and hearing impairment who were fitted with hearing aids later . Different screening programmes were modelled . The 35 dB HL better ear average hearing impairment level was found to be a good , robust and justifiable target group for screening and here the most efficient and practicable method was to use two questions in primary care concerning hearing problems and a hearing screen using a pure tone at 3 kHz 35 dB HL . The average cost of the screening programme was 13 pounds per person screened or about 100 pounds if treatment costs were included . Making the conservative assumption that identification gives an extra 9 years using hearing aids , the costs of screening and intervention were in the range of 800 - 1000 pounds per quality -adjusted life-year when using the Health Utilities Index and about 2500 pounds using the Short Form 6 Dimensions metric . CONCLUSIONS A simple systematic screen , using an audiometric screening instrument , has been shown to be acceptable to people in the age range 55 - 74 years , is likely to provide substantial benefit and may be cost-effective to those in that target group . Hearing screening appears to meet the National Screening Committee 's criteria in most respects , provided screening is targeted at those with at least 35 dB HL better ear average . Based on the research carried out here there is sufficient evidence to support a larger and more definitive study of hearing screening . Further research into who should be referred for and benefit from audiological assessment and provision of hearing aid in a primary care trust setting is needed as is investigation into screening devices and the various aspects of introducing such a programme Objective To examine the prevalence of outcome reporting bias — the selection for publication of a subset of the original recorded outcome variables on the basis of the results — and its impact on Cochrane review s. Design A nine point classification system for missing outcome data in r and omised trials was developed and applied to the trials assessed in a large , unselected cohort of Cochrane systematic review s. Research ers who conducted the trials were contacted and the reason sought for the non-reporting of data . A sensitivity analysis was undertaken to assess the impact of outcome reporting bias on review s that included a single meta- analysis of the review primary outcome . Results More than half ( 157/283 ( 55 % ) ) the review s did not include full data for the review primary outcome of interest from all eligible trials . The median amount of review outcome data missing for any reason was 10 % , whereas 50 % or more of the potential data were missing in 70 ( 25 % ) review s. It was clear from the publications for 155 ( 6 % ) of the 2486 assessable trials that the research ers had measured and analysed the review primary outcome but did not report or only partially reported the results . For reports that did not mention the review primary outcome , our classification regarding the presence of outcome reporting bias was shown to have a sensitivity of 88 % ( 95 % CI 65 % to 100 % ) and specificity of 80 % ( 95 % CI 69 % to 90 % ) on the basis of responses from 62 trialists . A third of Cochrane review s ( 96/283 ( 34 % ) ) contained at least one trial with high suspicion of outcome reporting bias for the review primary outcome . In a sensitivity analysis undertaken for 81 review s with a single meta- analysis of the primary outcome of interest , the treatment effect estimate was reduced by 20 % or more in 19 ( 23 % ) . Of the 42 meta-analyses with a statistically significant result only , eight ( 19 % ) became non-significant after adjustment for outcome reporting bias and 11 ( 26 % ) would have overestimated the treatment effect by 20 % or more . Conclusions Outcome reporting bias is an under-recognised problem that affects the conclusions in a substantial proportion of Cochrane review s. Individuals conducting systematic review s need to address explicitly the issue of missing outcome data for their review to be considered a reliable source of evidence . Extra care is required during data extraction , review ers should identify when a trial reports that an outcome was measured but no results were reported or events observed , and contact with trialists should be encouraged Auditory training has long been advocated to enhance communication but has never been time or cost-effective . This article describes the concepts underlying the development of a home-based , interactive adaptive computer program design ed to engage the adult hearing-impaired listener in the hearing-aid-fitting process , provide listening strategies , build confidence , and address cognitive changes characteristic of the aging process . An investigation using a between-group , within-subject design with pre- and post-test objective and subjective measures was conducted at five clinical sites . Sixty-five subjects were r and omly placed into two groups , one receiving LACE ( Listening and Communication Enhancement ) immediately following baseline testing and one serving as a control for one month and then receiving training as a crossover group . Results showed statistically significant improvements for the trained subjects on all but one of the outcome measures . Barriers facing the widespread implementation of home-based aural rehabilitation are discussed Background Although feedback on performance is generally thought to promote perceptual learning , the role and necessity of feedback remain unclear . We investigated the effect of providing varying amounts of positive feedback while listeners attempted to discriminate between three identical tones on learning frequency discrimination . Methodology /Principal Findings Using this novel procedure , the feedback was meaningless and r and om in relation to the listeners ' responses , but the amount of feedback provided ( or lack thereof ) affected learning . We found that a group of listeners who received positive feedback on 10 % of the trials improved their performance on the task ( learned ) , while other groups provided either with excess ( 90 % ) or with no feedback did not learn . Superimposed on these group data , however , individual listeners showed other systematic changes of performance . In particular , those with lower non-verbal IQ who trained in the no feedback condition performed more poorly after training . Conclusions / Significance This pattern of results can not be accounted for by learning models that ascribe an external teacher role to feedback . We suggest , instead , that feedback is used to monitor performance on the task in relation to its perceived difficulty , and that listeners who learn without the benefit of feedback are adept at self-monitoring of performance , a trait that also supports better performance on non-verbal IQ tests . These results show that ‘ perceptual ’ learning is strongly influenced by top-down processes of motivation and intelligence A software system , SPATS ( patent pending ) , that tests and trains important bottom-up and combined bottom-up/top-down speech-perception skills is described . Bottom-up skills are the abilities to identify the constituents of syllables : onsets , nuclei , and codas in quiet and noise as produced by eight talkers . Top-down skills are the abilities to use knowledge of linguistic context to identify words in spoken sentences . The sentence module in SPATS emphasizes combined bottom-up/top-down abilities in perceiving sentences in noise . The word-initial onsets , stressed nuclei , and word-final codas are ranked in importance and grouped into subsets based on their importance . Testing utilizes r and om presentation of all the items included in a subset . Training in Quiet ( SNR = 40 dB ) or in Noise ( SNR = 5 dB ) , is adaptively focused on individual listener 's learnable items of intermediate difficulty . Alternatively , SNR-adaption training uses Kaernbach 's algorithm to find the SNR required for a target percent correct . The unique sentence module trains the combination of bottom-up ( hearing ) with top-down ( use of linguistic context ) abilities to identify words in meaningful sentences in noise . Scoring in the sentence module is objective and automatic We assessed the effects of perceptual training of syllable identification in noise on nonsense syllable test ( NST ) performance of new ( Experiment 1 ) and experienced ( Experiment 2 ) hearing aid ( HA ) users with sensorineural hearing loss . In Experiment 1 , new HA users were r and omly assigned to either immediate training ( IT ) or delayed training ( DT ) groups . IT subjects underwent 8 weeks of at-home syllable identification training and in-laboratory testing , whereas DT subjects underwent identical in-laboratory testing without training . Training produced large improvements in syllable identification in IT subjects , whereas spontaneous improvement was minimal in DT subjects . DT subjects then underwent training and showed performance improvements comparable with those of the IT group . Training-related improvement in NST scores significantly exceeded improvements due to amplification . In Experiment 2 , experienced HA users received identical training and testing procedures as users in Experiment 1 . The experienced users also showed significant training benefit . Training-related improvements generalized to untrained voices and were maintained on retention tests . Perceptual training appears to be a promising tool for improving speech perception in new and experienced HA users This paper describes the first phase in the development of the Connected Speech Test ( CST ) . This test of intelligibility of everyday speech has been developed primarily for use as a criterion measure in investigations of hearing aid benefit . The test consists of 48 passages of conversationally produced connected speech . Each passage contains 25 key words for scoring . All passages are of equal intelligibility for the average normal hearer . Key words vary in intelligibility within a passage but span the same intelligibility range in all passages . Several passages are administered , and the results averaged , to yield a single intelligibility score . For pairs of scores , each based on mean performance across 4 r and omly-chosen passages , the 95 % critical difference is estimated to be about 14 rationalized arcsine units ( rau ) . The performance-intensity function for the CST has a slope of 12 rau/dB signal-to-babble ratio . Investigations of the test are continuing with hearing-impaired listeners Objectives : The goal of this study was to create and vali date a new set of sentence lists that could be used to evaluate the speech perception abilities of hearing-impaired listeners and cochlear implant ( CI ) users . Our intention was to generate a large number of sentence lists with an equivalent level of difficulty for the evaluation of performance over time and across conditions . Design : The AzBio sentence corpus includes 1000 sentences recorded from two female and two male talkers . The mean intelligibility of each sentence was estimated by processing each sentence through a five-channel CI simulation and calculating the mean percent correct score achieved by 15 normal-hearing listeners . Sentences from each talker were sorted by percent correct score , and 165 sentences were selected from each talker and were then sequentially assigned to 33 lists , each containing 20 Output:	Although significant generalisation of learning was shown to untrained measures of speech intelligibility ( 11/13 articles ) , cognition ( 1/1 articles ) and self-reported hearing abilities ( 1/2 articles ) , improvements were small and not robust . Where reported , compliance with computer-based auditory training was high , and retention of learning was shown at post-training follow-ups . Our findings demonstrate that published evidence for the efficacy of individual computer-based auditory training for adults with hearing loss is not robust and therefore can not be reliably used to guide intervention at this time .
MS22168	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Screening for colorectal cancer is widely recommended , but the preferred strategy remains unidentified . We aim ed to compare participation and diagnostic yield between screening with colonoscopy and with non-cathartic CT colonography . METHODS Members of the general population , aged 50 - 75 years , and living in the regions of Amsterdam or Rotterdam , identified via the registries of the regional municipal administration , were r and omly allocated ( 2:1 ) to be invited for primary screening for colorectal cancer by colonoscopy or by CT colonography . R and omisation was done per household with a minimisation algorithm based on age , sex , and socioeconomic status . Invitations were sent between June 8 , 2009 , and Aug 16 , 2010 . Participants assigned to CT colonography who were found to have one or more large lesions ( ≥10 mm ) were offered colonoscopy ; those with 6 - 9 mm lesions were offered surveillance CT colonography . The primary outcome was the participation rate , defined as number of invitees undergoing the examination relative to the total number of invitees . Diagnostic yield was calculated as number of participants with advanced neoplasia relative to the total number of invitees . Invitees and screening centre employees were not masked to allocation . This trial is registered in the Dutch trial register , number NTR1829 . FINDINGS 1276 ( 22 % ) of 5924 colonoscopy invitees participated , compared with 982 ( 34 % ) of 2920 CT colonography invitees ( relative risk [ RR ] 1·56 , 95 % CI 1·46 - 1·68 ; p<0·0001 ) . Of the participants in the colonoscopy group , 111 ( 9 % ) had advanced neoplasia of whom seven ( < 1 % ) had a carcinoma . Of CT colonography participants , 84 ( 9 % ) were offered colonoscopy , of whom 60 ( 6 % ) had advanced neoplasia of whom five ( < 1 % ) had a carcinoma ; 82 ( 8 % ) were offered surveillance . The diagnostic yield for all advanced neoplasia was 8·7 per 100 participants for colonoscopy versus 6·1 per 100 for CT colonography ( RR 1·46 , 95 % CI 1·06 - 2·03 ; p=0·02 ) and 1·9 per 100 invitees for colonoscopy and 2·1 per 100 invitees for CT colonography ( RR 0·91 , 0·66 - 2·03 ; p=0·56 ) . The diagnostic yield for advanced neoplasia of 10 mm or more was 1·5 per 100 invitees for colonoscopy and 2·0 per 100 invitees for CT colonography , respectively ( RR 0·74 , 95 % CI 0·53 - 1·03 ; p=0·07 ) . Serious adverse events related to the screening procedure were post-polypectomy bleedings : two in the colonoscopy group and three in the CT colonography group . INTERPRETATION Participation in colorectal cancer screening with CT colonography was significantly better than with colonoscopy , but colonoscopy identified significantly more advanced neoplasia per 100 participants than did CT colonography . The diagnostic yield for advanced neoplasia per 100 invitees was similar for both strategies , indicating that both techniques can be used for population -based screening for colorectal cancer . Other factors such as cost-effectiveness and perceived burden should be taken into account when deciding which technique is preferable . FUNDING Netherl and s Organisation for Health Research and Development , Centre for Translational Molecular Medicine , and the Nuts Ohra Foundation BACKGROUND & AIMS Data from r and omized controlled trials on the effects of screening colonoscopies on colorectal cancer ( CRC ) incidence and mortality are not available . Observational studies have suggested that colonoscopies strongly reduce the risk of CRC , but there is little specific evidence on the effects of screening colonoscopies . METHODS We performed a population -based case-control study of 3148 patients with a first diagnosis of CRC ( cases ) and 3274 subjects without CRC ( controls ) from the Rhine-Neckar region of Germany from 2003 to 2010 . Detailed information on previous colonoscopy and potential confounding factors was collected by st and ardized personal interviews . Self-reported information on colonoscopies and their indications was vali date d by medical records . We used multiple logistic regression to assess the association between colonoscopy conducted for specific indications within the past 10 years and risk of CRC . RESULTS A history of colonoscopy was associated with a reduced subsequent risk of CRC , independently of the indication for the examination . However , somewhat stronger associations were found for examinations with screening indications ( adjusted odds ratio [ OR ] 0.09 , 95 % confidence interval [ CI ] 0.07 - 0.13 ) than for examinations with diagnostic indications , such as positive fecal occult blood test result ( OR , 0.33 ; 95 % CI , 0.19 - 0.57 ) , surveillance after a preceding colonoscopy ( OR , 0.33 ; 95 % CI , 0.24 - 0.45 ) , rectal bleeding ( OR , 0.28 ; 95 % CI , 0.20 - 0.40 ) , abdominal symptoms ( OR , 0.15 ; 95 % CI , 0.10 - 0.21 ) , or other ( OR , 0.21 ; 95 % CI , 0.14 - 0.30 ) . Colonoscopy was also associated with a reduced risk of cancer in the right colon , regardless of the indication , although to a smaller extent than for other areas of the colon ( OR for screening colonoscopy , 0.22 ; 95 % CI , 0.14 - 0.33 ) . CONCLUSIONS In a population -based case-control study , the risk of CRC was strongly reduced up to 10 years after colonoscopy for any indication . Risk was particularly low after screening colonoscopy , even for cancer in the right colon BACKGROUND In r and omized trials , fecal occult-blood testing reduces mortality from colorectal cancer . However , the duration of the benefit is unknown , as are the effects specific to age and sex . METHODS In the Minnesota Colon Cancer Control Study , 46,551 participants , 50 to 80 years of age , were r and omly assigned to usual care ( control ) or to annual or biennial screening with fecal occult-blood testing . Screening was performed from 1976 through 1982 and from 1986 through 1992 . We used the National Death Index to obtain up date d information on the vital status of participants and to determine causes of death through 2008 . RESULTS Through 30 years of follow-up , 33,020 participants ( 70.9 % ) died . A total of 732 deaths were attributed to colorectal cancer : 200 of the 11,072 deaths ( 1.8 % ) in the annual-screening group , 237 of the 11,004 deaths ( 2.2 % ) in the biennial-screening group , and 295 of the 10,944 deaths ( 2.7 % ) in the control group . Screening reduced colorectal-cancer mortality ( relative risk with annual screening , 0.68 ; 95 % confidence interval [ CI ] , 0.56 to 0.82 ; relative risk with biennial screening , 0.78 ; 95 % CI , 0.65 to 0.93 ) through 30 years of follow-up . No reduction was observed in all-cause mortality ( relative risk with annual screening , 1.00 ; 95 % CI , 0.99 to 1.01 ; relative risk with biennial screening , 0.99 ; 95 % CI , 0.98 to 1.01 ) . The reduction in colorectal-cancer mortality was larger for men than for women in the biennial-screening group ( P=0.04 for interaction ) . CONCLUSIONS The effect of screening with fecal occult-blood testing on colorectal-cancer mortality persists after 30 years but does not influence all-cause mortality . The sustained reduction in colorectal-cancer mortality supports the effect of polypectomy . ( Funded by the Veterans Affairs Merit Review Award Program and others . ) Introduction : We conducted a cluster-r and omized trial aim ed at assessing the effect of the type of faecal occult blood , guaiac or immunochemical test on screening compliance . Methods : We sample d 130 general practitioners ( GPs ) who consented to participate in the trial . We r and omly allocated half of them to the guaiac ( Hemo-Fec ) and half to the immunochemical test ( OC-Hemodia ) . We sample d 2/10 of the GPs ' 50–75-year-old patients ( n=7332 ) and r and omly divided this population into half . One half was invited to be screened at the GP 's office and the other to the nearest gastroenterology ward . The principal outcome was the percentage of returned tests . Results : The immunochemical test had a compliance of 35.8 % and the guaiac of 30.4 % ( relative risk [ RR ] 1.20 ; 95 % confidence interval [ CI ] 1.02–1.44 ) . The difference was mostly due to a higher probability of returning the sample : 93.8 % and 88.6 % for immunochemical and guaiac , respectively ( RR 1.06 ; 95 % CI 1.02–1.10 ) . The guaiac test had a higher prevalence of positives ( 10.3 % versus 6.3 % , RR 0.603 ; 95 % CI 0.433–0.837 ) . There was a higher variability in the results obtained with the guaiac test compared with the immunochemical ( F[1 , 12 ] = 16.25 ; P=0.0017 ) . Conclusions : Compliance is more likely with the immunochemical than the guaiac test , independent of the provider . Guaiac tests show a higher variability of the results among centres . The successful implementation of a screening programme requires a period of st and ardization of the test reading in order to avoid unexpected work overload for colonscopy services BACKGROUND Data on the adherence rate to screening colonoscopy ( OC ) in the average-risk general population are limited and variable . Aim of this study was to compare the uptake of OC screening with that of fecal occult blood ( FOBT ) . METHODS A nationwide , population -based , multicentre , r and omized trial comparing attendance to OC with that to FOBT was performed . Sixty-four general practitioners ( GPs ) , overall including in their lists 9889 average-risk subjects aged 55 - 64 years , were r and omized between OC and FOBT screening programs . Eligible subjects were mailed a personal invitation letter co-signed by their GP and the coordinator of the area-reference GI centre . Attendance rate and detection rate for advanced neoplasia ( colorectal cancer , adenoma > 10 mm or with villous histology or high- grade dysplasia ) for each arm of the study were assessed . RESULTS The overall attendance rate was 18.7 % ( 1563/8378 eligible subjects ) . It was markedly lower in the OC than in the FOBT strategy ( 10 % vs. 27.1 % ; OR 0.28 , 95 % CI : 0.25 - 0.32 ; P<0.0001 ) . In particular , participation in OC screening arm was extremely low in South Italy ( 2.8 % ) , whilst it was higher in North- Central Italy ( 12.4 % ; P<0.0001 ) . Compliance to colonoscopy in those with a positive FOBT was only 58 % . Advanced neoplasia was detected in 28 ( 6.8 % ) patients in the OC arm and in 6 ( 18 % ) in those with a positive FOBT su bmi tted to OC . CONCLUSIONS The results of our study underline the difficulties and barriers to implement a OC population screening in Italy , at least through primary care . Although attendance to FOBT was higher , it was disappointingly less than 30 % . Significant actions to improve awareness amongst GPs and the population are a high priority BACKGROUND : The role of screening colonoscopy for colorectal ( CR ) neoplasia in average-risk population , remains to be determined . OBJECTIVES : To evaluate the prevalence and anatomic location of CR adenoma and carcinoma and the morbidity of colonoscopy in individuals at average risk for CR cancer ( CRC ) . METHODS : A retrospective prevalence study of subjects aged 40–80 yr , with no cancer-related symptoms , personal or family history of CR neoplasia , who underwent a colonoscopy . RESULTS : Enrolled were 1,177 persons ; 183 aged 40–49 yr ( young ) , 917 aged 50–75 yr , and 77 aged 76–80 yr ( elderly ) . The prevalence of overall CR neoplasia , advanced neoplasia , and cancer was 20.9 % , 6.3 % , and 1.1 % , respectively . In the 50–75 age group , the prevalence of overall adenoma , advanced ne Output:	Flexible sigmoidoscopy ( FS ) prevented CRC and led to the largest reduction in CRC mortality with a smaller but significant reduction in CRC mortality with the use of guaiac fecal occult blood tests ( gFOBTs ) . There was insufficient or low quality evidence to support the use of other screening tests , including colonoscopy , as well as changing the ages of initiation and cessation for CRC screening with gFOBTs in Ontario . Either annual or biennial screening using gFOBT reduces CRC-related mortality . Conclusion . The evidentiary base supports the use of FS or FOBT ( either annual or biennial ) to screen patients at average risk for CRC .
MS22169	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Human re source limitations are a challenge to the delivery of antiretroviral therapy ( ART ) in low-re source setting s. We conducted a cluster r and omized trial to assess the effect of community-based peer health workers ( PHW ) on AIDS care of adults in Rakai , Ug and a. Methodology /Principal Findings 15 AIDS clinics were r and omized 2∶1 to receive the PHW intervention ( n = 10 ) or control ( n = 5 ) . PHW tasks included clinic and home-based provision of counseling , clinical , adherence to ART , and social support . Primary outcomes were adherence and cumulative risk of virologic failure ( > 400 copies/mL ) . Secondary outcomes were virologic failure at each 24 week time point up to 192 weeks of ART . Analysis was by intention to treat . From May 2006 to July 2008 , 1336 patients were followed . 444 ( 33 % ) of these patients were already on ART at the start of the study . No significant differences were found in lack of adherence ( < 95 % pill count adherence risk ratio [ RR ] 0.55 , 95 % confidence interval [ CI ] 0.23–1.35 ; < 100 % adherence RR 1.10 , 95 % CI 0.94–1.30 ) , cumulative risk of virologic failure ( RR 0.81 , 95 % CI 0.61–1.08 ) or in shorter-term virologic outcomes ( 24 week virologic failure RR 0.93 , 95 % CI 0.65–1.32 ; 48 week , RR 0.83 , 95 % CI 0.47–1.48 ; 72 week , RR 0.81 , 95 % CI 0.44–1.49 ) . However , virologic failure rates ≥96 weeks into ART were significantly decreased in the intervention arm compared to the control arm ( 96 week failure RR 0.50 , 95 % CI 0.31–0.81 ; 120 week , RR 0.59 , 95 % CI 0.22–1.60 ; 144 week , RR 0.39 , 95 % CI 0.16–0.95 ; 168 week , RR 0.30 , 95 % CI 0.097–0.92 ; 192 week , RR 0.067 , 95 % CI 0.0065–0.71 ) . Conclusions / Significance A PHW intervention was associated with decreased virologic failure rates occurring 96 weeks and longer into ART , but did not affect cumulative risk of virologic failure , adherence measures , or shorter-term virologic outcomes . PHWs may be an effective intervention to sustain long-term ART in low-re source setting s. Trial Registration Clinical Trials.gov OBJECTIVES Marijuana was involved in 209,563 emergency department ( ED ) visits in 2006 , according to the Drug Abuse Warning Network . Although screening and brief intervention ( SBI ) has been effective in changing drinking among ED patients in a number of studies , tests of marijuana SBI in a pediatric emergency department ( PED ) have not yet been reported . The aim of this pilot study was to test whether SBI is effective in reducing marijuana consumption among youth and young adults presenting to a PED with a diverse range of clinical entities . METHODS A three-group r and omized controlled preliminary trial was structured to test 1 ) differences between Intervention ( Int ) and st and ard Assessed Control ( AC ) groups in marijuana consumption , from baseline to 12 months , and 2 ) the feasibility of adding a Nonassessed Control ( NAC ) group to evaluate regression to the mean and assessment reactivity . Patients aged 14 - 21 years in an urban , academic PED were screened during 2006 - 2007 , using st and ardized risk factor questions . Subjects were eligible if they used marijuana three or more times in the past 30 days , but were excluded for co-occurring high-risk alcohol use . Consented enrollees were r and omized to NAC , AC , and Int groups in a two-stage process that permitted blinding to status during assessment and follow-up . NACs received a re source h and out , written advice about marijuana use risks , and a 12-month follow-up appointment . ACs were assessed using st and ardized instruments and received re sources , written advice , and 3- and 12-month follow-up appointments . The Int group received assessment , re sources , written advice , 3- and 12-month appointments , a 20-minute structured conversation conducted by older peers , and a 10-day booster telephone call . A peer educator utilized a motivational style interview protocol adapted for adolescents to elicit daily life context and future goals , provide feedback , review pros and cons of marijuana use , assess readiness to change , evaluate strengths and assets , negotiate a contract for change , and make referrals to treatment and /or other re sources . Measurements included demographic information ; 30-day self-report of marijuana use ; attempts to quit , cut back , or change conditions of use ; and risk factor questions repeated at follow-up . RESULTS Among 7,804 PED patients screened , 325 were eligible ; 210 consented and enrolled ( Int , n = 68 ; AC , n = 71 ; NAC , n = 71 ) , with a 12-month follow-up rate of 71 % . For the primary objective , we compared Int to AC . At 12 months , Int participants were more likely to be abstinent for the past 30 days than ACs ( odds ratio [ OR ] for reported abstinence = 2.89 , 95 % confidence interval [ CI ] = 1.22 to 6.84 , p < 0.014 ) . The Int group had greater reduction in days used , baseline to 12 months , controlling for baseline ( Int = -7.1 vs. AC = -1.8 ) , were less likely to have been high among those who smoked ( OR = 0.39 , 95 % CI = 0.17 to 0.89 , p < 0.05 ) , and were more likely to receive referrals . In a linear regression model controlling for baseline use , NACs smoked 4 fewer days per month than ACs , but consumption was not significantly different , suggesting no assessment reactivity effect . CONCLUSIONS A preliminary trial of SBI promoted marijuana abstinence and reduced consumption among PED patients aged 14 - 21 years . A no-contact condition for the NAC group over the year after enrollment was insufficient to capture enrollees for follow-up across a range of baseline acuity Background Recent studies provide evidence for the effectiveness of Internet-based maintenance treatments for mental disorders . However , it is still unclear which participants might or might not profit from this particular kind of treatment delivery . Objective The study aim ed to identify moderators of treatment outcome in a transdiagnostic Internet-based maintenance treatment ( TIMT ) offered to patients after inpatient psychotherapy for mental disorders in routine care . Methods Using data from a r and omized controlled trial ( N=400 ) design ed to test the effectiveness of TIMT , we performed secondary analyses to identify factors moderating the effects of TIMT ( intervention ) when compared with those of a treatment-as-usual control condition . TIMT involved an online self-management module , asynchronous patient – therapist communication , a peer support group , and online-based progress monitoring . Participants in the control condition had unstructured access to outpatient psychotherapy , st and ardized outpatient face-to-face continuation treatment , and psychotropic management . Self-reports of psychopathological symptoms and potential moderators were assessed at the start of inpatient treatment ( T1 ) , at discharge from inpatient treatment/start of TIMT ( T2 ) , and at 3-month ( T3 ) and 12-month follow-up ( T4 ) . Results Education level , positive outcome expectations , and diagnoses significantly moderated intervention versus control differences regarding changes in outcomes between T2 and T3 . Only education level moderated change differences between T2 and T4 . The effectiveness of the intervention ( vs control ) was more pronounced among participants with a low ( vs high ) education level ( T2-T3 : B=–0.32 , SE 0.16 , P=.049 ; T2-T4 : B=–0.42 , SE 0.21 , P=.049 ) , participants with high ( vs low ) positive outcome expectations ( T2-T3 : B=–0.12 , SE 0.05 , P=.02 ) and participants with anxiety disorder ( vs mood disorder ) ( T2-T3 : B=–0.43 , SE 0.21 , P=.04 ) . Simple slope analyses revealed that despite some subgroups benefiting less from the intervention than others , all subgroups still benefited significantly . Conclusions This transdiagnostic Internet-based maintenance treatment might be suitable for a wide range of participants differing in various clinical , motivational , and demographic characteristics . The treatment is especially effective for participants with low education levels . These findings may generalize to other Internet-based maintenance treatments . Trial Registration International St and ard R and omized Controlled Trial Number ( IS RCT N ) : 28632626 ; http://www.controlled-trials.com/is rct n/pf/28632626 ( Archived by WebCite at http://www.webcitation.org/6IqZjTLrx ) Objective To evaluate the effectiveness of telephone based peer support in the prevention of postnatal depression . Design Multisite r and omised controlled trial . Setting Seven health regions across Ontario , Canada . Participants 701 women in the first two weeks postpartum identified as high risk for postnatal depression with the Edinburgh postnatal depression scale and r and omised with an internet based r and omisation service . Intervention Proactive individualised telephone based peer ( mother to mother ) support , initiated within 48 - 72 hours of r and omisation , provided by a volunteer recruited from the community who had previously experienced and recovered from self reported postnatal depression and attended a four hour training session . Main outcome measures Edinburgh postnatal depression scale , structured clinical interview-depression , state-trait anxiety inventory , UCLA loneliness scale , and use of health services . Results After web based screening of 21 470 women , 701 ( 72 % ) eligible mothers were recruited . A blinded research nurse followed up more than 85 % by telephone , including 613 at 12 weeks and 600 at 24 weeks postpartum . At 12 weeks , 14 % ( 40/297 ) of women in the intervention group and 25 % ( 78/315 ) in the control group had an Edinburgh postnatal depression scale score > 12 ( χ2=12.5 , P<0.001 ; number need to treat 8.8 , 95 % confidence interval 5.9 to 19.6 ; relative risk reduction 0.46 , 95 % confidence interval 0.24 to 0.62 ) . There was a positive trend in favour of the intervention group for maternal anxiety but not loneliness or use of health services . For ethical reasons , participants identified with clinical depression at 12 weeks were referred for treatment , result ing in no differences between groups at 24 weeks . Of the 221 women in the intervention group who received and evaluated their experience of peer support , over 80 % were satisfied and would recommend this support to a friend . Conclusion Telephone based peer support can be effective in preventing postnatal depression among women at high risk . Trial registration IS RCT N 68337727 The increasing prevalence of diabetes and obesity , growing health disparities , and shortage of bilingual and culturally trained health care professionals underscore the role of trained community health workers ( CHWs ) to provide economically sustainable and culturally relevant services . This prospect i ve r and omized design evaluated the relative effectiveness of a CHW intervention among Hispanic persons with newly diagnosed type 2 diabetes , as compared with usual clinic practice in three inner-city health centers . In sum , 189 Hispanic patients newly diagnosed with type 2 diabetes were r and omly assigned to one of three 6-month diabetes management approaches — CHW , case management , and st and ard provider care— and assessed for diabetes-related health measures and clinical indicators at baseline and postintervention . Participants in the CHW group achieved greater improvements than did the controls in program measures : health status , emergency department utilization , dietary habits , physical activity , and medication adherence . They also had 2.9 times greater odds of decreasing body mass index OBJECTIVE Demonstrate the effective use of community-based evidence for health promotion by Lady Health Workers ( LHWs ) in Sindh , Pakistan . METHODS A baseline study on mothers and children provided local evidence for risk communication tools design ed and tested by LHWs . The communities were r and omized to intervention and control . LHWs visited women before and after childbirth to discuss safe practice s in pregnancy , in the intervention group LHW using the new tools and in the control group using their st and ard procedures . A household survey and focus groups permitted assessment of the impact of the intervention . RESULTS Women in the intervention communities were more likely to attend prenatal checkups , to stop routine heavy work during pregnancy , to give colostrum to newborn babies , and to maintain exclusive breastfeeding for four months . Community focus groups confirmed a positive reaction to the tools . CONCLUSION Discussion by lay health workers of local evidence underlying safe motherhood messages improved uptake of protective health practice s. PRA Output:	Peer support is a broad and robust strategy for reaching groups that health services too often fail to engage .
MS22170	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Travellers are at risk of acquiring infectious diseases during travel , with risks differing by destination , travel and traveller characteristics . A pre-travel health consultation may minimize this risk . However , uptake of pre-travel health advice remains low . We investigated pre-travel health preparations and disease-specific risk behaviours among notified cases of selected travel-associated infectious diseases imported into Australia . Methods Prospect i ve enhanced surveillance of notified cases of typhoid , paratyphoid , measles , hepatitis A , hepatitis E , malaria and chikungunya was conducted in two Australian states between February 2013 and January 2014 . Details of pre-travel health preparation and disease-specific risk behaviours were collected . Results Among 180 cases associated with international travel , 28 % were < 18 years , 65 % were VFR travellers and 22 % were frequent travellers , having travelled ≥5 times in the past 5 years . 25 % had sought pre-travel advice from a healthcare provider , and 16 % reported a pre-travel vaccine . Seeking pre-travel health advice did not differ by immigrant status ( P = 0.22 ) or by reason for travel ( P = 0.13 ) but was more commonly sought by first time travellers ( P = 0.03 ) . Travellers visiting friends and relatives were more likely to report at-risk activities of brushing teeth with tap water ( P < 0.001 ) and eating uncooked food ( P = 0.03 ) during travel compared to other travellers . Conclusions Pre-travel health advice seeking practice s and vaccine uptake was suboptimal among cases of notified disease . The results of this study highlight the need for a better underst and ing of barriers to pre-travel health seeking , particularly among high risk travellers , to reduce the importation of infectious diseases into Australia Prebiotics are nondigestible food ingredients that encourage proliferation of selected groups of the colonic microflora , thereby altering the composition toward a more beneficial community . In the present study , the prebiotic potential of a novel galactooligosaccharide ( GOS ) mixture , produced by the activity of galactosyltransferases from Bifidobacterium bifidum 41171 on lactose , was assessed in vitro and in a parallel continuous r and omized pig trial . In situ fluorescent hybridization with 16S rRNA-targeted probes was used to investigate changes in total bacteria , bifidobacteria , lactobacilli , bacteroides , and Clostridium histolyticum group in response to supplementing the novel GOS mixture . In a 3-stage continuous culture system , the bifidobacterial numbers for the first 2 vessels , which represented the proximal and traverse colon , increased ( P < 0.05 ) after the addition of the oligosaccharide mixture . In addition , the oligosaccharide mixture strongly inhibited the attachment of enterohepatic Escherichia coli ( P < 0.01 ) and Salmonella enterica serotype Typhimurium ( P < 0.01 ) to HT29 cells . Addition of the novel mixture at 4 % ( wt : wt ) to a commercial diet increased the density of bifidobacteria ( P < 0.001 ) and the acetate concentration ( P < 0.001 ) , and decreased the pH ( P < 0.001 ) compared with the control diet and the control diet supplemented with inulin , suggesting a great prebiotic potential for the novel oligosaccharide mixture Daniel Maeusezahl and colleagues conducted a cluster-r and omized controlled trial in rural Bolivia of solar drinking water disinfection , and find only moderate compliance with the intervention and no evidence of reduction in diarrhea among children Background / Objectives : Prebiotics have attracted interest for their ability to positively affect the colonic microbiota composition , thus increasing resistance to infection and diarrhoeal disease . This study assessed the effectiveness of a prebiotic galacto-oligosaccharide mixture ( B-GOS ) on the severity and /or incidence of travellers ' diarrhoea ( TD ) in healthy subjects . Subjects/ Methods : The study was a placebo-controlled , r and omized , double blind of parallel design in 159 healthy volunteers , who travelled for minimum of 2 weeks to a country of low or high risk for TD . The investigational product was the B-GOS and the placebo was maltodextrin . Volunteers were r and omized into groups with an equal probability of receiving either the prebiotic or placebo . The protocol comprised of a 1 week pre-holiday period recording bowel habit , while receiving intervention and the holiday period . Bowel habit included the number of bowel movements and average consistency of the stools as well as occurrence of abdominal discomfort , flatulence , bloating or vomiting . A clinical report was completed in the case of diarrhoeal incidence . A post- study question naire was also completed by all subjects on their return . Results : Results showed significant differences between the B-GOS and the placebo group in the incidence ( P<0.05 ) and duration ( P<0.05 ) of TD . Similar findings occurred on abdominal pain ( P<0.05 ) and the overall quality of life assessment ( P<0.05 ) . Conclusions : Consumption of the tested galacto-oligosaccharide mixture showed significant potential in preventing the incidence and symptoms of TD BACKGROUND Travelers ' diarrhea ( TD ) is a significant problem for travelers . TD is treatable once it occurs , but few options for prevention exist . Probiotics have been studied for prevention or treatment of TD ; however , very few combination probiotics have been studied . Therefore , the purpose of this study was to determine if prophylactic use of an oral synbiotic could reduce the risk of acquiring TD and reduce antibiotic use if TD occurred . METHODS Healthy subjects traveling to an area of the world with an increased risk of TD were eligible . All subjects received pre-travel counseling and were provided antibiotics and antidiarrheals ( loperamide ) for use only if TD developed . The subjects were blinded and r and omized to take two capsules of placebo or oral synbiotic ( a combination of two probiotics and a prebiotic ) called Agri-King Synbiotic ( AKSB ) beginning 3 days prior to departure , daily while traveling , and for 7 days after return . All subjects kept symptom and medication diaries and su bmi tted a stool sample for pathogen carriage within 7 days of return . The study was powered to detect a 50 % reduction in the incidence of TD . RESULTS Of the 196 adults ( over 18 years of age ) enrolled in the study , 54.3 % were female and 80.9 % were younger than 60 years . The study r and omized 94 people to the AKSB arm and 102 to placebo . The incidence of TD was 54.5 % in the overall group with 55.3 % in the AKSB arm and 53.9 % in the placebo ( p = 0.8864 ) . Among the subjects who experienced diarrhea ( n = 107 ) there was no significant difference in the proportion of subjects that took antibiotics versus those that did not take antibiotics ( 35 % vs 29 % , p = 0.68 ) . AKSB was safe with no difference in toxicity between the two arms . CONCLUSIONS The prophylactic oral synbiotic was safe but did not reduce the risk of developing TD among travelers , nor did it decrease the duration of TD or the use of antibiotics when TD occurred Output:	Results and conclusions Travellers ' diarrhoea and use of pre/probiotics : There is no significant evidence to suggest the benefit of using pre or probiotics to prevent or treat TD . A new second generation of B-GOS prebiotics shows some potential in preventing the incidence and symptoms of TD but lack high levels of grade d evidence . The evidence behind water purification and diarrhoeal disease : Evidence suggests there is no direct correlation that water purification has an impact on diarrhoeal disease , although some studies underline the value of water purification . With new water purification products and methods being introduced a benefit could be found for publishing effectiveness against pathogen groups to improve comparison . Are travellers given good sanitary advice and do they follow it ? Within the clinical sector the advice provided and the outcomes of advice provision do not correlate with a reduction in TD as a variance can occur by travellers ' changes and behaviours towards the advice given . Following recommended advice and consuming higher risks foods do not correspond directly with levels of reported TD , suggesting attitudes and practice s deviate away from this advice when travelling
MS22171	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND AND OBJECTIVE Several studies have shown that periodontitis can complicate the severity of diabetes by worsening the degree of glycemic control . The purpose of this study was to determine the effect of full-mouth tooth extraction on glycemic control among type 2 diabetic patients . MATERIAL AND METHODS A total of 58 patients with type 2 diabetes mellitus and advanced periodontitis who were requiring extraction of all remaining teeth were r and omized consecutively into treatment ( full-mouth tooth extraction ) and control groups ( no treatment ) . Eight patients were lost to follow-up or reported use of antibiotics , leaving 50 patients to be included in the analysis . All patients had all their remaining teeth in a hopeless condition . Relevant data were collected , and glycosylated hemoglobin ( HbA(1c ) ) and fasting blood glucose levels were measured at baseline and at follow-up times of 3 and 6 mo . RESULTS At baseline , the mean ( SD ) HbA(1c ) level was 8.6 % ( 1.24 ) in the treatment group and 7.7 % ( 0.87 ) in the control group . In the treatment group , the mean HbA(1c ) level decreased significantly from 8.6 % at baseline to 7.4 % after 3 mo of denture treatment , and continued to decrease to 7.3 % after 6 mo . In the control group , the mean HbA(1c ) decreased from 7.7 % at baseline to 7.5 % after 3 mo , and remained almost the same after 6 mo . After adjusting for the baseline HbA(1c ) , the mean reduction in HbA(1c ) after 3 mo in the treatment group [ 1.23 % ( 0.79 ) ] was significantly higher than the mean reduction in the control group [ 0.28 % ( 0.87 ) ] . CONCLUSION Full-mouth tooth extraction result ed in an improvement in glycemic control among diabetic patients . Large-scale multicentre clinical trials are needed to confirm the current evidence The aim of this study was to evaluate changes in clinical parameters and levels of inflammatory biomarkers in plasma in periodontal patients with poorly controlled type 2 diabetes mellitus ( T2DM ) after non-surgical periodontal therapy . Twenty-eight poorly controlled T2DM patients were r and omly assigned to treatment with scaling and root planning ( SRP ) and SRP + subgingival minocycline administration . Clinical parameters , including the probing depth ( PD ) , bleeding on probing ( BOP ) , plaque score ( PS ) , clinical attachment level ( CAL ) , and plasma interleukin (IL)-6 , soluble receptor of advanced glycation end products ( sRAGE ) , chronic reactive protein ( CRP ) , and hemoglobin A1c ( HbA1c ) were measured before and after a 6-month treatment period . Significant changes in PD , BOP , PS , and CAL were found in both groups . The latent growth curve model showed an overall reduction in the log HbA1c level in the SRP group ( −0.082 , p = 0.033 ) . Small changes in the log sRAGE level and log CRP level in plasma were found in both groups . IL-6 in the plasma increased in the SRP group , but slightly decreased in the SRP+minocycline group ( 0.469 pg/ml , p = 0.172 ) . Non-surgical periodontal therapy with or without subgingival minocycline application may achieve significant periodontal improvement and moderate improvement in HbA1c , but had no significant effect on plasma levels of IL-6 , CRP , or sRAGE in patients with poorly controlled T2DM . For patients with both periodontal diseases and diabetes , non-surgical periodontal treatments may be helpful in their diabetic control In vitro and animal studies suggest a possible role for the tetracycline class of drugs in the inhibition of non-enzymatic protein glycation . We conducted a 3-month , r and omized placebo-controlled pilot clinical trial of conventional sub-gingival debridement ( periodontal therapy ) , combined with either a three month regimen of sub-antimicrobial-dose doxycycline ( SDD ) , a two week regimen of antimicrobial-dose doxycycline ( ADD ) , or placebo in 45 patients with long-st and ing type 2 diabetes ( mean duration 9 years ) and untreated chronic periodontitis . Subjects were taking stable doses of oral hypoglycemic medications and /or insulin . Treatment response was assessed by measuring hemoglobin A1c ( HbA1c ) , plasma glucose , and clinical periodontal disease measures . At one-month and three-month follow-up , clinical measures of periodontitis were decreased in all groups ( data to be presented elsewhere ) . At three months , mean HbA1c levels in the SDD group were reduced 0.9 % units from 7.2 % units±2.2 ( ±SD ) , to 6.3 % units±1.1 , which represents a 12.5 % improvement . In contrast , there was no significant change in HbA1c in the ADD ( 7.5%±2.0 to 7.8%±2.1 ) or placebo ( 8.5%±2.0 to 8.5%±2.6 ) groups . Mean HbA1c change from baseline was significantly greater in the SDD group compared with the ADD group ( p=0.04 ) but not placebo ( p=0.22 ) . Moreover , a larger proportion of subjects in the SDD group experienced improvement ( p<0.05 ) compared to the ADD or placebo groups . Mean plasma glucose levels were not significantly different between or within the groups . The results of this pilot study suggest that the treatment of periodontitis with sub-gingival debridement and 3-months of daily sub-antimicrobial-dose doxycycline may decrease HbA1c in patients with type 2 diabetes taking normally prescribed hypoglycemic agents AIM To evaluate associations between glycaemic control and periodontitis progression among Gullah African Americans with type-2 diabetes mellitus ( T2DM ) . MATERIAL S AND METHODS From an ongoing clinical trial among T2DM Gullah , we extracted a cohort previously in a cross-sectional study ( N=88 ) . Time from baseline ( previous study ) to follow-up ( trial enrollment , before treatment interventions ) ranged 1.93 - 4.08 years [ mean=2.99 , st and ard deviation (SD)=0.36 ] . We evaluated tooth site-level periodontitis progression [ clinical attachment loss ( CAL ) worsening of > or = 2 mm , periodontal probing depth ( PPD ) increases of > or = 2 mm and bleeding on probing ( BOP ) from none to present ] by glycaemic control status ( well-controlled = HbA(1c)<7 % , poorly-controlled = HbA(1c ) > or = 7 % ) using multivariable generalized estimating equations logistic regression , nesting tooth sites/person . RESULTS Poorly-controlled T2DM ( 68.18 % ) was more prevalent than well-controlled T2DM ( 31.82 % ) . Proportions of tooth sites/person with CAL progression between baseline and follow-up ranged 0.00 - 0.59 ( mean=0.12 , SD=0.12 ) , while PPD and BOP progression ranged 0.00 - 0.44 ( mean=0.09 , SD=0.11 ) and 0.00 - 0.96 ( mean=0.24 , SD=0.18 ) , respectively . Site-level PPD at baseline was a significant effect modifier of associations between poorly-controlled T2DM and site-level CAL and PPD progression [ adjusted odds ratios ( OR ) according to poorly-controlled T2DM among PPD at baseline=3 , 5 and 7 mm , respectively : CAL progression=1.93 , 2.64 , and 3.62 , PPD progression=1.98 , 2.76 , and 3.84 ; p<0.05 for all ] . Odds of site-level BOP progression were increased ( OR=1.24 ) for poorly-controlled T2DM , yet the results were not significant ( p=0.32 ) . CONCLUSIONS These findings from a distinct , homogenous population further support the clinical relevance of identifying patients with poor glycaemic control and periodontitis , particularly among those with disparities for both diseases BACKGROUND Systemic inflammation may impair vascular function , and epidemiologic data suggest a possible link between periodontitis and cardiovascular disease . METHODS We r and omly assigned 120 patients with severe periodontitis to community-based periodontal care ( 59 patients ) or intensive periodontal treatment ( 61 ) . Endothelial function , as assessed by measurement of the diameter of the brachial artery during flow ( flow-mediated dilatation ) , and inflammatory biomarkers and markers of coagulation and endothelial activation were evaluated before treatment and 1 , 7 , 30 , 60 , and 180 days after treatment . RESULTS Twenty-four hours after treatment , flow-mediated dilatation was significantly lower in the intensive-treatment group than in the control-treatment group ( absolute difference , 1.4 % ; 95 % confidence interval [ CI ] , 0.5 to 2.3 ; P=0.002 ) , and levels of C-reactive protein , interleukin-6 , and the endothelial-activation markers soluble E-selectin and von Willebr and factor were significantly higher ( P<0.05 for all comparisons ) . However , flow-mediated dilatation was greater and the plasma levels of soluble E-selectin were lower in the intensive-treatment group than in the control-treatment group 60 days after therapy ( absolute difference in flow-mediated dilatation , 0.9 % ; 95 % CI , 0.1 to 1.7 ; P=0.02 ) and 180 days after therapy ( difference , 2.0 % ; 95 % CI , 1.2 to 2.8 ; P<0.001 ) . The degree of improvement was associated with improvement in measures of periodontal disease ( r=0.29 by Spearman rank correlation , P=0.003 ) . There were no serious adverse effects in either of the two groups , and no cardiovascular events occurred . CONCLUSIONS Intensive periodontal treatment result ed in acute , short-term systemic inflammation and endothelial dysfunction . However , 6 months after therapy , the benefits in oral health were associated with improvement in endothelial function Studies indicate that a dual pathway between diabetes mellitus and periodontal disease exists . Elimination of periodontal infection by using systemic antibiotics in conjunction with scaling and root planing ( SRP ) improved metabolic control in diabetic patients , as defined by reduction in glycated haemoglobin or reduction in insulin requirements ( Grossi and Genco , 1998 ) . The aim of this r and omised pilot clinical trial was to determine if type 1 diabetes patients with periodontitis will experience a reduction in HbA1c levels when treated with locally delivered minocycline microspheres ( Arestin ) as an adjunct to scaling and root planing . Twenty adult patients with poorly controlled diabetes ( HbA1c 7.5 % ) and adult periodontitis , as determined by the presence of four teeth with 5 mm periodontal pockets , two of which had 6 - 9 mm pockets and bleeding on probing , were included in the study . All patients received full mouth SRP at baseline . Arestin was administered to all pockets > or = > or = 5 mm at baseline and again at 12 weeks in the test group . Probing depth ( PD ) , clinical attachment level ( CAL ) , plaque index ( PI ) , gingival index ( GI ) , and HbA1c were evaluated at baseline and at weeks 6 , 12 , 18 and 24 . The results demonstrated that local administration of Arestin as an adjunct to scaling and root planing is significantly more effective in reducing probing depths and providing a gain in clinical attachment levels than scaling and root planing alone in type 1 diabetic patients . Hb1Ac was reduced in all patients ; however the difference between the test and control groups was not significant BACKGROUND Periodontitis , a complication of diabetes mellitus ( DM ) , can induce or perpetuate systemic conditions . This double-masked , placebo-controlled study evaluated the effects of periodontal therapy ( scaling and root planing [ SRP ] ) on the serum levels of glycated hemoglobin ( HbA1c ) and on inflammatory biomarkers . METHODS Thirty subjects with type 2 DM and periodontitis were treated with SRP + placebo ( SRP ; N = 15 ) or with SRP + doxycycline ( SRP+Doxy ; N = 15 ) , 100 mg/day , for 14 days . Clinical and laboratory data were recorded at baseline and at 3 months after treatment . RESULTS After 3 months , the reduction in probing depth was 0.8 mm for the SRP group ( P < 0.01 ) and 1.1 mm for the SRP+Doxy group ( P < 0.01 ) followed by a 0.9 % ( SRP ; P = 0.17 ) and 1.5 % ( SRP+Doxy ; P < 0.01 ) reduction in HbA1c levels . A significant reduction in interleukin (IL)-6 ; interferon-inducible protein 10 ; sol Output:	Conclusions The meta‐ analysis showed that non‐surgical periodontal treatment improves metabolic control in patients with both periodontitis and diabetes
MS22172	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: This r and omized , double-blind , placebo-controlled study evaluated whether lamivudine given during late pregnancy can reduce hepatitis B virus ( HBV ) perinatal transmission in highly viraemic mothers . Mothers were r and omized to either lamivudine 100 mg or placebo from week 32 of gestation to week 4 postpartum . At birth , infants received recombinant HBV vaccine with or without HBIg and were followed until week 52 . One hundred and fifty mothers , with a gestational age of 26 - 30 weeks and serum HBV DNA > 1000 MEq/mL ( bDNA assay ) , were treated . A total of 141 infants received immunoprophylaxis at birth . In lamivudine-treated mothers , 56 infants received vaccine + HBIg ( lamivudine + vaccine + HBIg ) and 26 infants received vaccine ( lamivudine + vaccine ) . In placebo-treated mothers , 59 infants received vaccine + HBIg ( placebo + vaccine + HBIg ) . At week 52 , in the primary analyses where missing data was counted as failures , infants in the lamivudine + vaccine + HBIg group had a significant decrease in incidence of HBsAg seropositivity ( 10/56 , 18%vs 23/59 , 39 % ; P = 0.014 ) and in detectable HBV DNA ( 11/56 , 20%vs 27/59 , 46 % ; P = 0.003 ) compared to infants in the placebo + vaccine + HBIg group . Sensitivity analyses to evaluate the impact of missing data at week 52 result ing from a high dropout rate ( 13 % in the lamivudine + vaccine + HBIg group and 31 % in the placebo + vaccine + HBIg group ) remained consistent with the primary analysis in that lower transmission rates were still observed in the infants of lamivudine-treated mothers , but the differences were not statistically significant . No safety concerns were noted in the lamivudine-treated mothers or their infants . Results of this study suggest that lamivudine reduced HBV transmission from highly viraemic mothers to their infants who received passive/active immunization Thomas Campbell and colleagues report findings of a r and omized trial conducted in multiple countries regarding the efficacy of antiretroviral regimens with simplified dosing # # # What you need to know What is the role of arthroscopic surgery in degenerative knee disease ? An expert panel produced these recommendations based on a linked systematic review triggered by a r and omised trial published in The BMJ in June 2016 , which found that , among patients with a degenerative medial meniscus tear , knee arthroscopy was no better than exercise therapy . The panel make a strong recommendation against arthroscopy for degenerative knee disease . Box 1 shows all of the articles and evidence linked in this Rapid Recommendation package . The infographic provides an overview of the absolute benefits and harms of arthroscopy in st and ard GRADE format . Table 1 below shows any evidence that has emerged since the publication of this article . Box 1 # # # Linked articles in this BMJ Rapid Recommendations BACKGROUND In sub-Saharan Africa , the burden of human immunodeficiency virus (HIV)-associated tuberculosis is high . We conducted a trial with a 2-by-2 factorial design to assess the benefits of early antiretroviral therapy ( ART ) , 6-month isoniazid preventive therapy ( IPT ) , or both among HIV-infected adults with high CD4 + cell counts in Ivory Coast . METHODS We included participants who had HIV type 1 infection and a CD4 + count of less than 800 cells per cubic millimeter and who met no criteria for starting ART according to World Health Organization ( WHO ) guidelines . Participants were r and omly assigned to one of four treatment groups : deferred ART ( ART initiation according to WHO criteria ) , deferred ART plus IPT , early ART ( immediate ART initiation ) , or early ART plus IPT . The primary end point was a composite of diseases included in the case definition of the acquired immunodeficiency syndrome ( AIDS ) , non-AIDS-defining cancer , non-AIDS-defining invasive bacterial disease , or death from any cause at 30 months . We used Cox proportional models to compare outcomes between the deferred-ART and early-ART strategies and between the IPT and no-IPT strategies . RESULTS A total of 2056 patients ( 41 % with a baseline CD4 + count of ≥500 cells per cubic millimeter ) were followed for 4757 patient-years . A total of 204 primary end-point events were observed ( 3.8 events per 100 person-years ; 95 % confidence interval [ CI ] , 3.3 to 4.4 ) , including 68 in patients with a baseline CD4 + count of at least 500 cells per cubic millimeter ( 3.2 events per 100 person-years ; 95 % CI , 2.4 to 4.0 ) . Tuberculosis and invasive bacterial diseases accounted for 42 % and 27 % of primary end-point events , respectively . The risk of death or severe HIV-related illness was lower with early ART than with deferred ART ( adjusted hazard ratio , 0.56 ; 95 % CI , 0.41 to 0.76 ; adjusted hazard ratio among patients with a baseline CD4 + count of ≥500 cells per cubic millimeter , 0.56 ; 95 % CI , 0.33 to 0.94 ) and lower with IPT than with no IPT ( adjusted hazard ratio , 0.65 ; 95 % CI , 0.48 to 0.88 ; adjusted hazard ratio among patients with a baseline CD4 + count of ≥500 cells per cubic millimeter , 0.61 ; 95 % CI , 0.36 to 1.01 ) . The 30-month probability of grade 3 or 4 adverse events did not differ significantly among the strategies . CONCLUSIONS In this African country , immediate ART and 6 months of IPT independently led to lower rates of severe illness than did deferred ART and no IPT , both overall and among patients with CD4 + counts of at least 500 cells per cubic millimeter . ( Funded by the French National Agency for Research on AIDS and Viral Hepatitis ; TEMPRANO ANRS 12136 Clinical Trials.gov number , NCT00495651 . ) BACKGROUND The use of fixed-dose combination nucleoside reverse-transcriptase inhibitors ( NRTIs ) with a nonnucleoside reverse-transcriptase inhibitor or a ritonavir-boosted protease inhibitor is recommended as initial therapy in patients with human immunodeficiency virus type 1 ( HIV-1 ) infection , but which NRTI combination has greater efficacy and safety is not known . METHODS In a r and omized , blinded equivalence study involving 1858 eligible patients , we compared four once-daily antiretroviral regimens as initial therapy for HIV-1 infection : abacavir-lamivudine or tenofovir disoproxil fumarate (DF)-emtricitabine plus efavirenz or ritonavir-boosted atazanavir . The primary efficacy end point was the time from r and omization to virologic failure ( defined as a confirmed HIV-1 RNA level > or = 1000 copies per milliliter at or after 16 weeks and before 24 weeks , or > or = 200 copies per milliliter at or after 24 weeks ) . RESULTS A scheduled interim review by an independent data and safety monitoring board showed significant differences in virologic efficacy , according to the NRTI combination , among patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more . At a median follow-up of 60 weeks , among the 797 patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more , the time to virologic failure was significantly shorter in the abacavir-lamivudine group than in the tenofovir DF-emtricitabine group ( hazard ratio , 2.33 ; 95 % confidence interval , 1.46 to 3.72 ; P<0.001 ) , with 57 virologic failures ( 14 % ) in the abacavir-lamivudine group versus 26 ( 7 % ) in the tenofovir DF-emtricitabine group . The time to the first adverse event was also shorter in the abacavir-lamivudine group ( P<0.001 ) . There was no significant difference between the study groups in the change from the baseline CD4 cell count at week 48 . CONCLUSIONS In patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more , the times to virologic failure and the first adverse event were both significantly shorter in patients r and omly assigned to abacavir-lamivudine than in those assigned to tenofovir DF-emtricitabine . ( Clinical Trials.gov number , NCT00118898 . OBJECTIVE To compare the efficacy and safety of fixed-dose abacavir/lamivudine ( ABC/3TC ) and tenofovir/emtricitabine ( TDF/FTC ) with ritonavir-boosted atazanavir ( ATV/r ) in treatment-naïve Japanese patients with HIV-1 infection . METHODS A 96-week multicenter , r and omized , open-label , parallel group pilot study was conducted . The endpoints were times to virologic failure , safety event and regimen modification . RESULTS 109 patients were enrolled and r and omly allocated ( 54 patients received ABC/3TC and 55 patients received TDF/FTC ) . All r and omized subjects were analyzed . The time to virologic failure was not significantly different between the two arms by 96 weeks ( HR , 2.09 ; 95 % CI , 0.72 - 6.13 ; p=0.178 ) . Both regimens showed favorable viral efficacy , as in the intention-to-treat population , 72.2 % ( ABC/3TC ) and 78.2 % ( TDF/FTC ) of the patients had an HIV-1 viral load < 50 copies/mL at 96 weeks . The time to the first grade 3 or 4 adverse event and the time to the first regimen modification were not significantly different between the two arms ( adverse event : HR 0.66 ; 95 % CI , 0.25 - 1.75 , p=0.407 ) ( regimen modification : HR 1.03 ; 95 % CI , 0.33 - 3.19 , p=0.964 ) . Both regimens were also well-tolerated , as only 11.1 % ( ABC/3TC ) and 10.9 % ( TDF/FTC ) of the patients discontinued the allocated regimen by 96 weeks . Clinical ly suspected abacavir-associated hypersensitivity reactions occurred in only one ( 1.9 % ) patient in the ABC/3TC arm . CONCLUSION Although insufficiently powered to show non-inferiority of viral efficacy of ABC/3TC relative to TDF/FTC , this pilot trial suggested that ABC/3TC with ATV/r is a safe and efficacious initial regimen for HLA-B*5701-negative patients , such as the Japanese population BACKGROUND Preexposure prophylaxis with antiretroviral drugs has been effective in the prevention of human immunodeficiency virus ( HIV ) infection in some trials but not in others . METHODS In this r and omized , double-blind , placebo-controlled trial , we assigned 2120 HIV-negative women in Kenya , South Africa , and Tanzania to receive either a combination of tenofovir disoproxil fumarate and emtricitabine ( TDF-FTC ) or placebo once daily . The primary objective was to assess the effectiveness of TDF-FTC in preventing HIV acquisition and to evaluate safety . RESULTS HIV infections occurred in 33 women in the TDF-FTC group ( incidence rate , 4.7 per 100 person-years ) and in 35 in the placebo group ( incidence rate , 5.0 per 100 person-years ) , for an estimated hazard ratio in the TDF-FTC group of 0.94 ( 95 % confidence interval , 0.59 to 1.52 ; P=0.81 ) . The proportions of women with nausea , vomiting , or elevated alanine aminotransferase levels were significantly higher in the TDF-FTC group ( P=0.04 , P<0.001 , and P=0.03 , respectively ) . Rates of drug discontinuation because of hepatic or renal abnormalities were higher in the TDF-FTC group ( 4.7 % ) than in the placebo group ( 3.0 % , P=0.051 ) . Less than 40 % of the HIV-uninfected women in the TDF-FTC group had evidence of recent pill use at visits that were matched to the HIV-infection window for women with seroconversion . The study was stopped early , on April 18 , 2011 , because of lack of efficacy Output:	Tenofovir/emtricitabine is likely to increase stillbirth/early neonatal death and early premature delivery compared with zidovudine/lamivudine , but certainty is low when they are not coprescribed with lopinavir/ritonavir . Other outcomes are likely similar between antiretrovirals .
MS22173	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To investigate the effect of low-intensity acenocoumarol treatment ( target INR 1.5 to 2.0 ) on the frequency and severity of migraine attacks . BACKGROUND The positive effect of anticoagulation on migraine has been described in case reports and observational studies . METHODS We conducted a r and omized , open , crossover study in migraine patients . After a run-in period of 8 weeks , all patients received acenocoumarol or propranolol during a period of 12 weeks and , after a washout period of 2 weeks , propranolol or acenocoumarol during a second period of 12 weeks . RESULTS Nineteen patients fulfilling the criteria were included . In 12 patients with complete data collection , only one good responder could be noted . In the other patients , treatment with low-intensity acenocoumarol did not show improvement of migraine symptoms compared with the run-in period . Treatment with propranolol showed a trend towards improvement compared with the run-in period . No serious adverse events were observed . CONCLUSIONS Overall , low-intensity acenocoumarol treatment has no prophylactic effect in migraine patients OBJECTIVE This multi-center pilot study compared the efficacy of onabotulinumtoxinA with topiramate ( a Food and Drug Administration approved and widely accepted treatment for prevention of migraine ) in individuals with chronic migraine ( CM ) . METHODS A total of 59 subjects with CM were r and omly assigned to one of 2 groups : Group 1 ( n = 30 ) received topiramate plus placebo injections , Group 2 ( n = 29 ) received onabotulinumtoxinA injections plus placebo tablets . Subjects maintained daily headache diaries over a 4-week baseline period and a 12-week active study period . The primary endpoint was the Physician Global Assessment , which measured the treatment responder rate and indicated improvement in both groups over 12 weeks . Secondary endpoints , measured at weeks 4 and 12 , included headache days per month , migraine days , headache-free days , days on acute medication , severity of headache episodes , Migraine Impact & Disability Assessment , Headache Impact Test , effectiveness of and satisfaction with current treatment on the amount of medication needed , and the frequency and severity of migraine symptoms . At 12 weeks subjects were re-evaluated and tapered off oral study medications over a 2-week time period . Subjects not reporting a > 50 % reduction of headache frequency at 12 weeks were invited to participate in a 12-week open label extension study with onabotulinumtoxinA. Of these , 20 subjects , 9 from the Topiramate Group and 11 from the OnabotulinumtoxinA Group , volunteered for this extension from weeks 14 to 26 . RESULTS This study demonstrated positive benefit for both onabotulinumtoxinA and topiramate in subjects with CM . Overall , the results were statistically significant within groups but not between groups . By week 26 , subjects had a reduction of headache days per month compared with baseline . This was a significant within-group finding . CONCLUSION OnabotulinumtoxinA and topiramate demonstrated similar efficacy for subjects with CM as determined by Global Physician Assessment and supported by multiple secondary endpoint measures The calcium-entry blocker flunarizine ( Sibelium ; Janssen ) was compared with the beta-adrenoreceptor-blocking agent propranolol in the prophylaxis of migraine . Fifty-eight patients were entered into a double-blind 4-month treatment trial . Patients in whom beta-blockers were contraindicated were excluded from the trial . At the end of the trial 28 patients had received 10 mg flunarizine at night during the study , 29 patients had received 60 mg propranolol 3 times a day and 1 patient was withdrawn . Both groups responded well ; and there was a 4-fold drop in frequency of attacks . There was no significant difference between the two groups in terms of patient profile , onset of response to therapy , final response to therapy , incidence of dropout from the trial or incidence of side-effects . Side-effects for flunarizine were weight gain ( 9 patients ) and tiredness ( 6 ) , and for propranolol sleep disturbances including nightmares ( 6 ) , tiredness ( 8) , mental changes ( e.g. irritability ) ( 3 ) and weight gain ( 4 ) . Both flunarizine and propranolol are useful drugs for migraine prophylaxis and can be used effectively as first-line drugs . The low incidence of generally mild side-effects with flunarizine may make it preferable to many of the agents at present in use for migraine prophylaxis Acute treatment of menstrual migraine ( MM ) attacks is often incomplete and unsatisfactory , and perimenstrual prophylaxis with triptans , oestrogen supplementation or naproxen sodium may be needed for decreasing frequency and severity of the attack . In this pilot , open-label , non-r and omised , parallel group study we evaluated , in 38 women with a history of MM , the efficacy of frovatriptan ( n=14 ) 2.5 mg per os or transdermal oestrogens ( n=10 ) 25 μg or naproxen sodium ( n=14 ) 500 mg per os once-daily for the short-term prevention of MM . All treatments were administered in the morning for 6 days , beginning 2 days before the expected onset of menstrual headache . All women were asked to fill in a diary card , in the absence of ( baseline ) and under treatment , in order to score headache severity . All women reported at least one episode of MM at baseline . During treatment all patients taking transdermal oestrogens or naproxen sodium and 13 out of the 14 patients ( 93 % ) taking frovatriptan had at least one migraine attack ( p=0.424 ) . Daily incidence of migraine was significantly ( p=0.045 ) lower under frovatriptan than under transdermal oestrogens or NS . At baseline , the overall median score of headache severity was 4.6 , 4.2 and 4.3 in the group subsequently treated with frovatriptan , transdermal oestrogens and naproxen sodium , respectively ( p=0.819 ) . During treatment the median score was significantly lower under frovatriptan ( 2.5 ) than under transdermal oestrogens ( 3.0 ) and naproxen sodium ( 3.9 , p=0.049 ) . This was evident also for each single day of observation ( p=0.016 ) . Among treatments differences were particularly evident for the subgroup of patients with true MM ( n=22 ) and for frovatriptan vs. naproxen sodium . This study suggests that short-term prophylaxis of MM with frovatriptan may be more effective than that based on transdermal oestrogens or naproxen sodium AIM Topiramate is a small molecule widely used for the treatment of epilepsy , migraine , bipolar disorders and alcoholism , and its availability as a generic formulation could significantly reduce the National Health Service expenditure . A generic formulation , available in Italy under the trademark Sincronil , recently showed superimposable blood levels , after oral administration to healthy volunteers , with the reference formulation . In the present study we report the results of an open label , parallel group , r and omized , controlled study performed to evaluate the efficacy , tolerability and impact on disability of two different formulations of topiramate ( Sincronil and Topamax ) in patients with migraine without aura . METHODS Sixty patients aged between 18 and 65 years , suffering from migraine without aura with an attack frequency of 3 - 15 attacks/month were enrolled and received , after a titration phase lasting 20 days , r and omly either Sincronil or Topamax at the dose of 25 mg twice daily for 3 months . RESULTS Fifteen out of the 30 patients who were administered Sincronil reported an improvement in the clinical condition , with a decrease in the frequency of attacks at the 3rd month of treatment higher than 50 % with respect to the run-in period , 9 reported their clinical condition as being substantially unchanged and 6 reported that they had suspended the treatment within the first 4 weeks of therapy due to side effects . Among the 24 patients who continued treatment up to the 3rd month , the frequency of attacks during the 3rd month of treatment was significantly decreased from 7 ± 3.6 to 3.7 ± 3.7 ( P<0.0001 ) , migraine severity was reduced from 2.5 ± 0.5 to 1.7 ± 0.7 ( P<0.0005 ) and the MIDAS score was reduced from 14.3 ± 4.9 to 8.6 ± 5.5 ( P<0.0001 ) . Sixteen out of the 30 patients who were administered Topamax reported an improvement in the clinical condition with a reduction in the attack frequency at the 3rd month of treatment higher than 50 % with respect to the run-in period , 10 reported a substantially unchanged clinical condition and 4 stopped the treatment within the first weeks due to side effects . Among the 26 patients who continued treatment up to the 3rd month , headache frequency during the 3rd month of treatment was significantly reduced , from 7.3 ± 2.6 to 3.5 ± 2.7 ( P<0.0001 ) , migraine severity decreased from 2.4 ± 0.6 to 1.6 ± 0.8 ( P<0.0005 ) and the MIDAS score from 14.1 ± 4.2 to 6.8 ± 4.8 ( P<0.0001 ) . CONCLUSION In conclusion , in this study Topamax ( reference product ) and Sincronil ( generic formulation ) have proven therapeutically equivalent and both products were well tolerated The clinical efficacy of flunarizine and of propranolol for the prevention of migraine attacks was assessed in a multicenter double-blind study lasting four months which was preceded by a single-blind placebo period of one month . For both drugs , more than half of the patients judged the effect to be good or very good . When considering the patients ' daily logs , both drugs produced a significant reduction of the number of attacks . Propranolol furthermore significantly reduced the severity of attacks and the number of analgesics used during the attacks . In both groups no severe side effects were observed Migraine can not be cured and the aim , shared with the patient , is to minimise the impact of the illness on the patient 's life and lifestyle . The aim of prophylaxis is to reduce the number of migraine attacks . Prophylaxis should be considered when appropriately used acute management gives inadequate control of symptoms . The efficacy and safety of topiramate 50 mg/d and thioctic acid ( α-lipoic acid ) 300 mg/d either as monotherapy or in combination were investigated as migraine prophylactic agents . Forty secondary school migraineur girls were enrolled in the study . The study was conducted in two phases , a prospect i ve baseline phase and 1-month treatment phase . Combined topiramate/thioctic acid therapy was more effective than either topiramate or thioctic acid monotherapy as a migraine-preventive treatment . Combined topiramate/thioctic acid therapy decreased the mean monthly migraine frequency from 5.86 ± 1.2 to 2.6 ± 0.98 ( p ⩽ 0.05 ) , topiramate ( 50 mg/d ) from 5.71 ± 1.4 to 4.75 ± 1.5 and thioctic acid ( 300 mg/d ) from 5.68 ± 1.6 to 5.22 ± 1.8 . Reduction in mean monthly migraine days was also significantly greater in the group receiving combined topiramate/thioctic acid ( from 12.32 ± 1.85 to 5.74 ± 1.1 ) compared to those receiving either topiramate 50 mg/d ( from 12.7 ± 1.34 to 11.85 ± 1.35 ) or thioctic acid 300 mg/d ( from 12.5 ± 1.72 to 11.65 ± 1.44 ) . The responder rate ( % of patients showing ⩾50 % reduction in monthly migraine frequency ) was 85 % in patients receiving combined topiramate/thioctic acid therapy compared to 30 % and 20 % in patients receiving either topiramate or thioctic acid , respectively . The incidence of adverse events was higher in patients receiving topiramate ( 50 mg/d ) monotherapy . The most common adverse events were nausea , fatigue , paraesthesia and taste perversion . We conclude that combined topiramate/thioctic acid therapy is more effective and better tolerated than topiramate monotherapy . The combination has lower monthly medication costs compared to the traditionally used topiramate 100 mg monotherapy In patients with migraine with or without aura the prophylactic effect of amitriptyline ( AMT ) and venlafaxine ( VLF ) was compared in a r and omized double-blind crossover study . Intolerable side effects result ed in drop out of five patients on AMT ( due to hypersomnia , difficulty in concentration and orthostatic hypotension ) and one patient on VLF ( because of nausea and vomiting ) . Following the run-in period the patients ( n = 52 ) were r and omly treated with one of the study medications for 1 Output:	Conclusions The majority of comparative , prophylactic migraine RCTs do not include a placebo arm . Failure to include a placebo arm may result in failure to demonstrate efficacy of potentially effective migraine-prophylactic agents .
MS22174	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Professional societies recommend shared decision making ( SDM ) for prostate cancer screening , however , most efforts have promoted informed rather than shared decision making . The objective of this study is to 1 ) examine the effects of a prostate cancer screening intervention to promote SDM and 2 ) determine whether framing prostate information in the context of other clearly beneficial men ’s health services affects decisions . Methods We conducted two separate r and omized controlled trials of the same prostate cancer intervention ( with or without additional information on more clearly beneficial men ’s health services ) . For each trial , we enrolled a convenience sample of 2 internal medicine practice s , and their interested physicians and male patients with no prior history of prostate cancer ( for a total of 4 practice s , 28 physicians , and 128 men across trials ) . Within each practice site , we r and omized men to either 1 ) a video-based decision aid and research er-led coaching session or 2 ) a highway safety video . Physicians at each site received a 1-hour educational session on prostate cancer and SDM . To assess intervention effects , we measured key components of SDM , intent to be screened , and actual screening . After finding that results did not vary by trial , we combined data across sites , adjusting for the r and om effects of both practice and physician . Results Compared to an attention control , our prostate cancer screening intervention increased men ’s perceptions that screening is a decision ( absolute difference + 41 % ; 95 % CI 25 to 57 % ) and men ’s knowledge about prostate cancer screening ( absolute difference + 34 % ; 95 % CI 19 % to 50 % ) , but had no effect on men ’s self-reported participation in shared decisions or their participation at their preferred level . Overall , the intervention decreased screening intent ( absolute difference −34 % ; 95 % CI −50 % to −18 % ) and actual screening rates ( absolute difference −22 % ; 95 % CI −38 to −7 % ) with no difference in effect by frame . Conclusions SDM interventions can increase men ’s knowledge , alter their perceptions of prostate cancer screening , and reduce actual screening . However , they may not guarantee an increase in shared decisions . Trial registration # ABSTRACT Despite increased interest among the public in breast cancer genetic risk and genetic testing , there are limited services to help women make informed decisions about genetic testing . This study , conducted with female callers ( N = 279 ) to the National Cancer Institute 's ( NCI 's ) Atlantic Region Cancer Information Service ( CIS ) , developed and evaluated a theory-based , educational intervention design ed to increase callers ' underst and ing of the following : ( a ) the kinds of information required to determine inherited risk ; ( b ) their own personal family history of cancer ; and ( c ) the benefits and limitations of genetic testing . Callers requesting information about breast/ovarian cancer risk , risk assessment services , and genetic testing were r and omized to either : ( 1 ) st and ard care or ( 2 ) an educational intervention . Results show that the educational intervention reduced intention to obtain genetic testing among women at average risk and increased intention among high-risk women at 6 months . In addition , high monitors , who typically attend to and seek information , demonstrated greater increases in knowledge and perceived risk over the 6-month interval than low monitors , who typically are distracted from information . These findings suggest that theoretically design ed interventions can be effective in helping women underst and their cancer risk and appropriate risk assessment options and can be implemented successfully within a service program like the CIS Purpose . To conduct a pilot test of a decision aid design ed to help patients choose among currently recommended colorectal cancer screening programs . Methods . R and omized controlled trial comparing a patient decision aid based on multi criteria decision-making theory with a simple educational intervention . Patient population . 96 patients at average risk for colorectal cancer seen in an Internal Medicine practice in Rochester , New York . Outcome measures . The two primary outcome measures were patient decision process and the decision outcome . Patient decision process was assessed using the decisional conflict scale . Decision outcome was defined as the proportion of colorectal cancer screening plans carried out . Results . After controlling for the effects of the physicians in a factorial analysis of variance , patients who used the decision aid had lower decisional conflict regarding colorectal cancer screening decisions ( F ratio6.47 , P = 0.01 ) due to increased knowledge , better clarity of values , and higher ratings of the quality of the decisions they made . There was no difference between the groups in decision outcomes : 52 % of patients in the control group and 49 % in the experimental group completed planned screening tests ( P = 1.0 ) . Conclusions . In a pilot study , a multi criteria -based patient decision aid for colorectal cancer screening improved patients ’ decision-making processes but had no effect on the implementation of screening plans There is an ever-growing trend toward more patient involvement in making health care decisions . This trend has been accompanied by the development of “ informed decision-making ” interventions to help patients become more engaged and comfortable with making these decisions . We describe the effects of a prostate cancer screening decision aid on knowledge , beliefs about screening , risk perception , control preferences , decisional conflict , and decisional anxiety . Data were collected from 200 males aged 50–70 years in the general population who r and omly were assigned to exposure to the decision aid or no exposure as a control condition . A Solomon four-group design was used to test for possible pretest sensitization effects and to assess the effects of exposure to the decision aid . No significant pretest sensitization effects were found . Analysis of the exposure effects found that knowledge increased significantly for those exposed to the decision aid compared with those unexposed . Exposure to the decision aid also had some influence on decreasing both decisional conflict and decisional anxiety . Decision aids can play an important role in increasing patients ' knowledge and decreasing anxiety when asked to make health care decisions Background Whether early detection and treatment of prostate cancer ( PCa ) will reduce disease-related mortality remains uncertain . As a result , tools are needed to facilitate informed decision making . While there have been several decision aids ( DAs ) developed and tested , very few have included an exercise to help men clarify their values and preferences about PCa screening . Further , only one DA has utilized an interactive web-based format , which allows for an expansion and customization of the material . We describe the development of two DAs , a booklet and an interactive website , each with a values clarification component and design ed for use in diverse setting s. Methods We conducted two feasibility studies to assess men 's ( 45 - 70 years ) Internet access and their willingness to use a web- vs. a print-based tool . The booklet was adapted from two previous versions evaluated in r and omized controlled trials ( RCTs ) and the website was created to closely match the content of the revised booklet . Usability testing was conducted to obtain feedback regarding draft versions of the material s. The tools were also review ed by a plain language expert and the interdisciplinary research team . Feedback on the content and presentation led to iterative modifications of the tools . Results The feasibility studies confirmed that the Internet was a viable medium , as the majority of men used a computer , had access to the Internet , and Internet use increased over time . Feedback from the usability testing on the length , presentation , and content of the material s was incorporated into the final versions of the booklet and website . Both the feasibility studies and the usability testing highlighted the need to address men 's informed decision making regarding screening . Conclusions Informed decision making for PCa screening is crucial at present and may be important for some time , particularly if a definitive recommendation either for or against screening does not emerge from ongoing prostate cancer screening trials . We have detailed our efforts at developing print- and web-based DAs to assist men in determining how to best meet their PCa screening preferences . Following completion of our ongoing RCT design ed to test these material s , our goal will be to develop a dissemination project for the more effective tool . Trial Registration OBJECTIVE Screening asymptomatic men for prostate cancer is controversial and informed decision making is recommended . Within two prostate cancer screening programs , we evaluated the impact of a print-based decision aid ( DA ) on decision-making outcomes . METHODS Men ( N=543 ) were 54.9 ( SD=8.1 ) years old and 61 % were African-American . The 2(booklet type : DA vs. usual care (UC)) × 2(delivery mode : Home vs. Clinic ) r and omized controlled trial assessed decisional and screening outcomes at baseline , 2-months , and 13-months . RESULTS Intention-to-treat linear regression analyses using generalized estimating equations revealed that DA participants reported improved knowledge relative to UC ( B=.41 , p<.05 ) . For decisional conflict , per- protocol analyses revealed a group by time interaction ( B=-.69 , p<.05 ) , indicating that DA participants were less likely to report decisional conflict at 2-months compared to UC participants ( OR=.49 , 95 % CI : .26-.91 , p<.05 ) . CONCLUSION This is the first r and omized trial to evaluate a DA in the context of free mass screening , a challenging setting in which to make an informed decision . The DA was highly utilized by participants , improved knowledge and reduced decisional conflict . PRACTICE IMPLICATION S These results are valuable in underst and ing ways to improve the decisions of men who seek screening and can be easily implemented within many setting OBJECTIVE Genetic testing is increasingly part of routine clinical care for women with a family history of breast cancer . Given their substantially elevated risk for breast cancer , BRCA1/BRCA2 mutation carriers must make the difficult decision whether or not to opt for risk reducing mastectomy . To help BRCA1/2 carriers make this decision , the authors developed a computer-based interactive decision aid that was tested against usual care in a r and omized controlled trial . DESIGN After the completion of genetic counseling , 214 female ( aged 21 - 75 ) BRCA1/BRCA2 mutation carriers were r and omized to Usual Care ( UC ; N = 114 ) or Usual Care plus Decision Aid ( DA ; N = 100 ) arms . UC participants received no additional intervention . DA participants were sent the CD-ROM DA to view at home . MAIN OUTCOME MEASURES The authors measured final management decision , decisional conflict , decisional satisfaction , and receipt of risk reducing mastectomy at 1- , 6- , and 12-months postr and omization . RESULTS Longitudinal analyses revealed that the DA was effective among carriers who were initially undecided about how to manage their breast cancer risk . Within this group , the DA led to an increased likelihood of reaching a management decision ( OR = 3.09 , 95 % CI = 1.62 , 5.90 ; p < .001 ) , decreased decisional conflict ( B = -.46 , z = -3.1 , p < 002 ) , and increased satisfaction ( B = .27 , z = 3.1 , p = .002 ) compared to UC . Among carriers who had already made a management decision by the time of r and omization , the DA had no benefit relative to UC . CONCLUSION These results demonstrate that BRCA1/BRCA2 mutation carriers who are having difficulty making a breast cancer risk management decision can benefit from adjunct decision support Background Patients are being encouraged to go online to obtain health information and interact with their health care systems . However , a 2014 survey found that less than 60 % of American adults aged 65 and older use the Internet , with much lower usage among black and Latino seniors compared with non-Hispanic white seniors , and among older versus younger seniors . Objective Our aims were to ( 1 ) identify race/ethnic and age cohort disparities among seniors in use of the health plan ’s patient portal , ( 2 ) determine whether race/ethnic and age cohort disparities exist in access to digital devices and preferences for using email- and Web-based modalities to interact with the health care system , ( 3 ) assess whether observed disparities in preferences and patient portal use are due simply to barriers to access and inability to use the Internet , and ( 4 ) learn whether older adults not currently using the health plan ’s patient portal or website have a potential interest in doing so in the future and what kind of support might be best suited to help them . Methods We conducted two studies of seniors aged 65 - 79 years . First , we used administrative data about patient portal account status and utilization in 2013 for a large cohort of English-speaking non-Hispanic white ( n=183,565 ) , black ( n=16,898 ) , Latino ( n=12,409 ) , Filipino ( n=11,896 ) , and Chinese ( n=6314 ) members of the Kaiser Permanente Northern California health plan . Second , we used data from a mailed survey conducted in 2013 - 2014 with a stratified r and om sample of this population ( final sample : 849 non-Hispanic white , 567 black , 653 Latino , 219 Filipino , and 314 Chinese ) . These data were used to examine race/ethnic and age disparities in patient portal use and readiness and preferences for using digital communication for health-related purpose s. Results Adults aged 70 - 74 and 75 - 79 were significantly less likely than 65 - 69 year olds to be registered to use the patient portal , and among those registered , to have used the portal to send messages , view lab test results , or order prescription refills . Across all age groups , non-Hispanic whites and Chinese seniors were significantly more likely than black , Latino , and Filipino seniors to be registered and to have performed these actions . The survey found that black , Latino , and Filipino seniors and those 75 years old and older were significantly less likely to own digital devices ( eg , computers , smartphones ) , use the Internet and email , and be able and willing to use digital technology to perform health care-related tasks , including obtaining health information , than non-Hispanic whites , Chinese , and younger seniors ( aged 65 - 69 ) , respectively . The preference for using non-digital modalities persisted even among Internet users . Conclusions Health plans , government agencies , and other organizations that serve diverse groups of seniors should include social determinants such as race/ethnicity and age when monitoring tr Output:	Conclusions The diversity of the US population is represented in a majority of cancer-related PtDA RCTs , but fewer studies have tailored PtDAs to address the multiple social disadvantages that may impact patients ’ participation in SDM .
MS22175	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Diet is an important factor in colorectal carcinogenesis ; thus , dietary supplements may have a role in colorectal cancer prevention . OBJECTIVE The objective was to establish the relative luminal , epithelial , and epigenetic consequences of prebiotic , probiotic , and synbiotic dietary supplementation in humans . DESIGN This was a r and omized , double-blind , placebo-controlled , 4-wk crossover trial of resistant starch and Bifidobacterium lactis , either alone or as a combined synbiotic preparation , in 20 human volunteers . Rectal biopsy , feces , and serum sample s were collected . The rectal mucosal endpoints were DNA methylation at 16 CpG isl and loci and LINE-1 , epithelial proliferation ( Ki67 immunohistochemistry ) , and crypt cellularity . The fecal endpoints were short-chain fatty acid concentrations , pH , ammonia , and microbiological profiles ( by denaturing gradient gel electrophoresis and sequencing ) . Serum endpoints were a panel of cytokines and high-sensitivity C-reactive protein . RESULTS Seventeen subjects completed the entire study . The synbiotic intervention fostered a significantly different fecal stream bacterial community than did either the prebiotic ( P = 0.032 ) or the probiotic ( P = 0.001 ) intervention alone , in part because of a greater proportion of patients harboring fecal Lachnospiraceae spp . These changes developed in the absence of any significant differences in fecal chemistry . There were no differences in epithelial kinetics . CONCLUSIONS This synbiotic supplementation with B. lactis and resistant starch , in the doses used , induced unique changes in fecal microflora but did not significantly alter any other fecal , serum , or epithelial variables . This trial was registered in the Australian New Zeal and Clinical Trials Registry at www.anzctr.org.au as ACTRN012606000115538 Background : Hyperactive Wnt signaling is frequently observed in colorectal cancer . Higher intakes of dietary fiber [ nondigestible carbohydrates ( NDCs ) ] and the fermentation product butyrate are protective against colorectal cancer and may exert their preventative effects via modulation of the Wnt pathway . Objectives : We investigated the effects of supplementing healthy individuals with 2 NDCs [ resistant starch ( RS ) and polydextrose ] on fecal calprotectin concentrations and Wnt pathway – related gene expression . In addition , we determined whether effects on secreted frizzled-related protein 1 ( SFRP1 ) expression are mediated via the epigenetic mechanisms DNA methylation and microRNA expression . Design : In a r and omized , double-blind , placebo-controlled trial ( the Dietary Intervention , Stem cells and Colorectal Cancer ( DISC ) Study ) , 75 healthy participants were supplemented with RS and /or polydextrose or placebo for 50 d in a 2 × 2 factorial design . Pre- and postintervention stool sample s and rectal mucosal biopsies were collected and used to quantify calprotectin and expression of 12 Wnt-related genes , respectively . The expression of 10 microRNAs predicted to target SFRP1 was also quantified by quantitative reverse transcriptase-polymerase chain reaction , and DNA methylation was quantified at 7 CpG sites within the SFRP1 promoter region by pyrosequencing . Results : NDC supplementation did not affect fecal calprotectin concentration . SFRP1 mRNA expression was reduced by both RS ( P = 0.005 ) and polydextrose ( P = 0.053 ) . RS and polydextrose did not affect SFRP1 methylation or alter the expression of 10 microRNAs predicted to target SFRP1 . There were no significant interactions between RS and polydextrose . Conclusions : RS and polydextrose supplementation did not affect fecal calprotectin concentrations . Downregulation of SFRP1 with RS and polydextrose could result in increased Wnt pathway activity . However , effects on Wnt pathway activity and downstream functional effects in the healthy large-bowel mucosa remain to be investigated . The DISC Study was registered at clinical trials.gov as NCT01214681 A global loss of cytosine methylation in DNA has been implicated in a wide range of diseases . There is growing evidence that modifications in DNA methylation can be brought about by altering the intake of methyl donors such as folate . We examined whether long-term daily supplementation with 0.8 mg of folic acid would increase global DNA methylation compared with placebo in individuals with elevated plasma homocysteine . We also investigated if these effects were modified by MTHFR C677 T genotype . Two hundred sixteen participants out of 818 subjects who had participated in a r and omized double-blind placebo-controlled trial were selected , pre-stratified on MTHFR C677 T genotype and matched on age and smoking status . They were allocated to receive either folic acid ( 0.8 mg/d ; n = 105 ) or placebo treatment ( n = 111 ) for three years . Peripheral blood leukocyte DNA methylation and serum and erythrocyte folate were assessed . Global DNA methylation was measured using liquid chromatography-t and em mass spectrometry and expressed as a percentage of 5-methylcytosines versus the total number of cytosine . There was no difference in global DNA methylation between those r and omized to folic acid and those in the placebo group ( difference = 0.008 , 95%CI = −0.05,0.07 , P = 0.79 ) . There was also no difference between treatment groups when we stratified for MTHFR C677 T genotype ( CC , n = 76 ; CT , n = 70 ; TT , n = 70 ) , baseline erythrocyte folate status or baseline DNA methylation levels . In moderately hyperhomocysteinemic men and women , long-term folic acid supplementation does not increase global DNA methylation in peripheral blood leukocytes . Clinical Trials.gov Background and aims : A low dietary folate intake can cause genomic DNA hypomethylation and may increase the risk of colorectal neoplasia . The hypothesis that folic acid supplementation increases DNA methylation in leucocytes and colorectal mucosa was tested in 31 patients with histologically confirmed colorectal adenoma using a r and omised , double blind , placebo controlled , parallel design . Methods : Subjects were r and omised to receive either 400 μg/day folic acid supplement ( n = 15 ) or placebo ( n = 16 ) for 10 weeks . Genomic DNA methylation , serum and erythrocyte folate , and plasma homocysteine concentrations were measured at baseline and post intervention . Results : Folic acid supplementation increased serum and erythrocyte folate concentrations by 81 % ( 95 % confidence interval ( CI ) 57–104 % ; p<0.001 v placebo ) and 57 % ( 95 % CI 40–74 % ; p<0.001 v placebo ) , respectively , and decreased plasma homocysteine concentration by 12 % ( 95 % CI 4–20 % ; p = 0.01 v placebo ) . Folic acid supplementation result ed in increases in DNA methylation of 31 % ( 95 % CI 16–47 % ; p = 0.05 v placebo ) in leucocytes and 25 % ( 95 % CI 11–39 % ; p = 0.09 v placebo ) in colonic mucosa . Conclusions : These results suggest that DNA hypomethylation can be reversed by physiological intakes of folic acid Purpose : This study evaluated the effects of black raspberries ( BRBs ) on biomarkers of tumor development in the human colon and rectum including methylation of relevant tumor suppressor genes , cell proliferation , apoptosis , angiogenesis , and expression of Wnt pathway genes . Experimental Design : Biopsies of adjacent normal tissues and colorectal adenocarcinomas were taken from 20 patients before and after oral consumption of BRB powder ( 60 g/d ) for 1–9 weeks . Methylation status of promoter regions of five tumor suppressor genes was quantified . Protein expression of DNA methyltransferase 1 ( DNMT1 ) and genes associated with cell proliferation , apoptosis , angiogenesis , and Wnt signaling were measured . Results : The methylation of three Wnt inhibitors , SFRP2 , SFRP5 , and WIF1 , upstream genes in Wnt pathway , and PAX6a , a developmental regulator , was modulated in a protective direction by BRBs in normal tissues and in colorectal tumors only in patients who received BRB treatment for an average of 4 weeks , but not in all 20 patients with 1–9 weeks of BRB treatment . This was associated with decreased expression of DNMT1 . BRBs modulated expression of genes associated with Wnt pathway , proliferation , apoptosis , and angiogenesis in a protective direction . Conclusions : These data provide evidence of the ability of BRBs to demethylate tumor suppressor genes and to modulate other biomarkers of tumor development in the human colon and rectum . While demethylation of genes did not occur in colorectal tissues from all treated patients , the positive results with the secondary endpoints suggest that additional studies of BRBs for the prevention of colorectal cancer in humans now appear warranted . Clin Cancer Res ; 17(3 ) ; 598–610 . © 2010 AACR Background / Aims : Low folate intake may increase risk of colorectal cancer by altering gene-specific methylation in the colon . We determined whether supplementation with physiological doses of folate could alter methylation in the oestrogen receptor 1 ( ESR1 ) and mutL homolog 1 ( MLH1 ) genes in colonic mucosa of subjects with colorectal adenoma . Methods : This was a r and omised , double-blind , placebo-controlled trial . Subjects received either 400 µg/day folic acid ( n = 15 ) or placebo ( n = 14 ) for 10 weeks . Blood and colonic tissue sample s were collected at baseline and after intervention to determine biomarkers of folate and vitamin B12 status , MTHFR C677 T and MS A2756 G genotypes , and ESR1 and MLH1 methylation . Results : Although serum and red cell folate increased ( p < 0.001 vs. placebo ) and plasma homocysteine decreased ( p = 0018 vs. placebo ) in the folic acid group , there were no significant changes in ESR1 ( p = 0.649 vs. placebo ) or MLH1 ( p = 0.211 vs. placebo ) methylation . There was a significant effect of gender on ESR1 methylation ( p = 0.004 ) and significant gender and genotype ( MTHFR C677 T and MS A2756 G ) interactions ( p = 0.04 and p = 0.014 , respectively ) that were independent of treatment group allocation . Conclusions : Short-term folate supplementation in physiological doses decreases plasma homocysteine but has no effect on ESR1 and MLH1 methylation in colonic mucosa of individuals with adenoma . Further studies to investigate the interactions between gender , genotype and DNA methylation suggested in this study are warranted BACKGROUND Methylation of genomic DNA is dependent on an adequate supply of folate coenzymes . Previous data support the hypothesis that abnormal DNA methylation plays an integral role in carcinogenesis . To date , no studies assessing the effect of inadequate folate status on DNA methylation in older women ( aged > 63 y ) have been reported . OBJECTIVE The effect of moderate folate depletion followed by folate repletion on leukocyte genomic DNA methylation was investigated in elderly women ( aged 60 - 85 y ) to evaluate whether DNA methylation could be used as a functional indicator of folate status . DESIGN Healthy , postmenopausal women ( n = 33 ) consumed a moderately folate-depleted diet ( 118 microg folate/d ) for 7 wk , followed by 7 wk of folate repletion with 200 or 415 microg/d , each provided as 2 different dietary treatments for a total of 4 treatment groups ( n = 30 ) . Leukocyte DNA methylation was determined on the basis of the ability of DNA to incorporate [(3)H]methyl groups from labeled S:-adenosylmethionine in an in vitro assay . RESULTS Incorporation of [(3)H]methyl groups increased significantly ( P : = 0.0025 ) in response to folate depletion , suggesting undermethylation of DNA . No significant changes were detected in [(3)H]methyl incorporation in any group over the 7-wk repletion period compared with postdepletion values . CONCLUSIONS DNA methylation status may be used as a functional indicator of moderately depleted folate status . The slow response to the repletion diets observed suggests that normalization of DNA methylation after moderate folate Output:	In summary , there is limited evidence from intervention studies of effects of dietary factors , other than folic acid , on DNA methylation patterns in humans .
MS22176	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVES This was a r and omized controlled pilot trial to evaluate the effectiveness of cupping therapy for neck pain in video display terminal ( VDT ) workers . METHODS Forty VDT workers with moderate to severe neck pain were recruited from May , 2011 to February , 2012 . Participants were r and omly allocated into one of the two interventions : 6 sessions of wet and dry cupping or heating pad application . The participants were offered an exercise program to perform during the participation period . A 0 to 100 numeric rating scale ( NRS ) for neck pain , measure yourself medical outcome profile 2 score ( MYMOP2 score ) , cervical spine range of motion ( C-spine ROM ) , neck disability index ( NDI ) , the EuroQol health index ( EQ-5D ) , short form stress response inventory ( SRI-SF ) and fatigue severity scale ( FSS ) were assessed at several points during a 7-week period . RESULTS Compared with a heating pad , cupping was more effective in improving pain ( adjusted NRS difference : -1.29 [ 95 % CI -1.61 , -0.97 ] at 3 weeks ( p=0.025 ) and -1.16 [ -1.48 , -0.84 ] at 7 weeks ( p=0.005 ) ) , neck function ( adjusted NDI difference : -0.79 [ -1.11 , -0.47 ] at 3 ( p=0.0039 ) and 7 weeks ( p<0.0001 ) ) and discomfort ( adjusted MYMOP2 difference score : -0.72 [ -1.04 to -0.40 ] at 3 weeks and -0.92 [ -1.24 , -0.60 ] at 7 weeks ) . Significant improvement in EQ-5D was observed at 7 weeks ( 1.0 [ 0.88 , 1.0 ] with cupping and 0.91 [ 0.86 , 0.91 ] with heating pad treatment , p=0.0054 ) . Four participants reported mild adverse events of cupping . CONCLUSION Two weeks of cupping therapy and an exercise program may be effective in reducing pain and improving neck function in VDT workers Introduction . Cupping has been used since antiquity in the treatment of pain conditions . In this pilot study , we investigated the effect of traditional cupping therapy on chronic nonspecific neck pain ( CNP ) and mechanical sensory thresholds . Methods . Fifty CNP patients were r and omly assigned to treatment ( TG , n = 25 ) or waiting list control group ( WL , n = 25 ) . TG received a single cupping treatment . Pain at rest ( PR ) , pain related to movement ( PM ) , quality of life ( SF-36 ) , Neck Disability Index ( NDI ) , mechanical detection ( MDT ) , vibration detection ( MDT ) , and pressure pain thresholds ( PPT ) were measured before and three days after a single cupping treatment . Patients also kept a pain and medication diary ( PaDi , MeDi ) during the study . Results . Baseline characteristics were similar in the two groups . After cupping TG reported significantly less pain ( PR : −17.9 mm VAS , 95%CI −29.2 to −6.6 ; PM : −19.7 , 95%CI −32.2 to −7.2 ; PaDi : −1.5 points on NRS , 95%CI −2.5 to −0.4 ; all P < 0.05 ) and higher quality of life than WL ( SF-36 , Physical Functioning : 7.5 , 95%CI 1.4 to 13.5 ; Bodily Pain : 14.9 , 95%CI 4.4 to 25.4 ; Physical Component Score : 5.0 , 95%CI 1.4 to 8.5 ; all P < 0.05 ) . No significant effect was found for NDI , MDT , or VDT , but TG showed significantly higher PPT at pain- areas than WL ( in lg(kPa ) ; pain-maximum : 0.088 , 95%CI 0.029 to 0.148 , pain-adjacent : 0.118 , 95%CI 0.038 to 0.199 ; both P < 0.01 ) . Conclusion . A single application of traditional cupping might be an effective treatment for improving pain , quality of life , and hyperalgesia in CNP Abstract Objectives : To evaluate the effectiveness and safety of wet cupping therapy as a single treatment for persistent nonspecific low back pain ( PNSLBP ) . Design : R and omized controlled trial comparing wet cupping versus no treatment in PNSLBP . Setting : Outpatient clinic in three secondary care hospitals in Saudi Arabia . Patients : Eighty eligible participants with PNSLBP for at least 3 months were r and omly allocated to an intervention group ( n=40 ) or to a control group ( n=40 ) . Interventions : Six wet cupping sessions within 2 weeks , each of which were done at two bladder meridian ( BL ) acupuncture points among BL23 , BL24 , and BL25 . Only acetaminophen was allowed as a rescue treatment in both groups . Outcome measures : The Numeric Rating Scale ( NRS ) , McGill Present Pain Intensity ( PPI ) , and Oswestry Disability Question naire ( ODQ ) were used as outcome measures . Numbers of acetaminophen tablets taken were compared at 4 weeks from baseline . Adverse events were recorded . Results : At the end of the intervention , statistically significant differences in the three outcome measures favoring the wet cupping group compared with the control group were seen : NRS score , 29.2 ( 95 % confidence interval [ CI ] , 24.6–33.8 ) versus 57.9 ( 95 % CI , 53.3–62.6 ) , respectively ; PPI score , 1.17 ( 95 % CI , 0.96–1.4 ) versus 2.3 ( 95 % CI , 2.1– 2.7 ) ; and ODQ score , 19.6 ( 95 % CI , 16.5–22.7 ) versus 35.4 ( 95 % CI , 32.3–38.5 ) ( p=0.0001 ) . This improvement continued for another 2 weeks after the end of the intervention . Acetaminophen was used less in the wet cupping group , but this difference was not statistically significant . No adverse events were reported . Conclusions : Wet cupping is potentially effective in reducing pain and improving disability associated with PNSLBP at least for 2 weeks after the end of the wet cupping period . Placebo-controlled trials are needed The purpose of this study was to evaluate the effect of laser acupuncture ( LA ) and soft cupping on low back pain . In this study , the subjects were r and omly assigned to two groups : active group ( real LA and soft cupping ) and placebo group ( sham laser and soft cupping ) . Visual analog scale ( VAS ) and Ryodoraku were used to evaluate the effect of treatment on low back pain in this trial . Laser , 40 mW , wavelength 808 nm , pulse rate 20 Hz , was used to irradiate Weizhong ( BL40 ) and Ashi acupoints for 10 minutes . And the Ryodoraku values were measured 2 times , that is , before and 15 minutes after treatment . The results show that there were significant difference between the first day baseline and the fifth day treatment in VAS in the two groups . Therefore , LA combined with soft cupping or only soft cupping was effective on low back pain . However , the Ryodoraku values of Bladder Meridian of the placebo group have been decreased apparently , and did n't come back to their original values . It means that “ cupping ” plays the role of “ leak or purge ” in traditional Chinese medicine ( TCM ) . On the other h and , the Ryodoraku values of Bladder Meridian of the active group have been turned back to almost their original values ; “ mend or reinforcing ” effect is attributed to the laser radiation Background : Chronic neck pain is a major public health burden with only limited evidence for the effectiveness of complementary therapies . This study aim ed to test the efficacy of cupping massage in patients with neck pain . Patients and Methods : Patients with chronic non-specific neck pain were r and omly assigned to cupping massage or a wait list control . The intervention group received 5 cupping massages on a twice-weekly basis while the control patients continued their usual treatments . The primary outcome measure was neck pain intensity ( 0 - 100 mm visual analogue scale ( VAS ) ) after 3 weeks . Secondary outcomes included pain on movement , functional disability , health-related quality of life , mechanical detection and pain thresholds and adverse events . Results : 50 patients ( 52.6 ± 10.3 years , 92 % female ) were r and omised to either cupping massage or a wait list ( N = 25 each ) . Patients in the cupping group reported significantly less neck pain post intervention ( difference per protocol -14.3 mm , 95 % confidence interval ( CI ) -27.7 to -1.0 , p = 0.037 ; difference intention-to-treat -10.8 mm , 95 % CI -21.5 to -0.1 , p = 0.047 ) . Significant group differences in favour of the intervention were further found for pain on movement ( p = 0.019 ) and functional disability ( p < 0.001 ) , the quality -of-life subscales pain ( p = 0.002 ) and mental health ( p = 0.003 ) and the mental component summary ( p = 0.036 ) . Changes were also found for pressure pain sensitivity at the site of maximal pain ( p = 0.022 ) . Five adverse events were reported . Conclusions : Cupping massage appears to be effective in reducing pain and increasing function and quality of life in patients with chronic non-specific neck pain . More rigorous studies are needed to confirm and extend these results Chronic neck pain is a major public health problem with very few evidence -based complementary treatment options . This study aim ed to test the efficacy of 12 weeks of a partner-delivered home-based cupping massage , compared to the same period of progressive muscle relaxation in patients with chronic non-specific neck pain . Patients were r and omly assigned to self-directed cupping massage or progressive muscle relaxation . They were trained and asked to undertake the assigned treatment twice weekly for 12 weeks . Primary outcome measure was the current neck pain intensity ( 0–100 mm visual analog scale ; VAS ) after 12 weeks . Secondary outcome measures included pain on motion , affective pain perception , functional disability , psychological distress , wellbeing , health-related quality of life , pressure pain thresholds and adverse events . Sixty one patients ( 54.1±12.7 years ; 73.8%female ) were r and omized to cupping massage ( n = 30 ) or progressive muscle relaxation ( n = 31 ) . After treatment , both groups showed significantly less pain compared to baseline however without significant group differences . Significant effects in favor of cupping massage were only found for wellbeing and pressure pain thresholds . In conclusion , cupping massage is no more effective than progressive muscle relaxation in reducing chronic non-specific neck pain . Both therapies can be easily used at home and can reduce pain to a minimal clinical ly relevant extent . Cupping massage may however be better than PMR in improving well-being and decreasing pressure pain sensitivity but more studies with larger sample s and longer follow-up periods are needed to confirm these results . Trial Registration Clinical Trials.gov Introduction Cupping is used in various traditional medicine forms to relieve pain in musculoskeletal diseases . The aim of this study was to investigate the effectiveness of cupping in relieving the symptoms of knee osteoarthritis ( OA ) . Methods In a two-group , r and omized controlled exploratory pilot study patients with a clinical ly and radiological confirmed knee OA ( Kellgren-Lawrence Grading Scale : 2 - 4 ) and a pain intensity > 40 mm on a 100 mm visual analogue scale ( VAS ) were included . 40 Patients were r and omized to either 8 sessions of pulsatile dry cupping within 4 weeks or no intervention ( control ) . Paracetamol was allowed on dem and for both groups . Outcomes were the Western Ontario and McMaster Universities Osteoarthritis ( WOMAC ) score , the pain intensity on a VAS ( 0 mm = no pain to 100 mm = maximum intensity ) and Quality of Life ( SF-36 ) 4 and 12 weeks after r and omization . Use of Paracetamol was documented within the 4-week treatment period . Analyses were performed by analysis of covariance adjusting for the baseline value for each outcome . Results 21 patients were allocated to the cupping group ( 5 male ; mean age 68 ± SD 7.2 ) and 19 to the control group ( 8 male ; 69 ± 6.8 ) . After 4 weeks the WOMAC global score improved significantly more in the cupping group with a mean of 27.7 ( 95 % confidence interval 22.1 ; 33.3 ) compared to 42.2 ( 36.3 ; 48.1 ) in the control group ( p = 0.001 ) . After 12 weeks the WOMAC global score were still significantly different in favor for cupping ( 31.0 ( 24.9 ; 37.2 ) vs. 40.8 ( 34.4 ; 47.3 ) p = 0.032 ) , however the WOMAC subscores for pain and stiffness were not significant anymore . Significantly better outcomes in the cupping group were also observed for pain intensity on VAS and for the SF-36 Physical Component Scale compared to the control group after 4 and 12 Output:	Cupping therapy has shown positive results on chronic back pain . There is no st and ardization in the treatment protocol . The main assessed outcomes were pain intensity , physical incapacity , quality of life and nociceptive threshold before the mechanical stimulus . cupping therapy is a promising method for the treatment of chronic back pain in adults .
MS22177	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objective To evaluate the effects of water versus beverages sweetened with non‐nutritive sweeteners ( NNS ) on body weight in subjects enrolled in a year‐long behavioral weight loss treatment program . Methods The study used a r and omized equivalence design with NNS or water beverages as the main factor in a trial among 303 weight‐stable people with overweight and obesity . All participants participated in a weight loss program plus assignment to consume 24 ounces ( 710 ml ) of water or NNS beverages daily for 1 year . Results NNS and water treatments were non‐equivalent , with NNS treatment showing greater weight loss at the end of 1 year . At 1 year subjects receiving water had maintained a 2.45 ± 5.59 kg weight loss while those receiving NNS beverages maintained a loss of 6.21 ± 7.65 kg ( P < 0.001 for difference ) . Conclusions Water and NNS beverages were not equivalent for weight loss and maintenance during a 1‐year behavioral treatment program . NNS beverages were superior for weight loss and weight maintenance in a population consisting of regular users of NNS beverages who either maintained or discontinued consumption of these beverages and consumed water during a structured weight loss program . These results suggest that NNS beverages can be an effective tool for weight loss and maintenance within the context of a weight management program BACKGROUND The rising prevalence of obesity in children has been linked in part to the consumption of sugar-sweetened drinks . Our aim was to examine this relation . METHODS We enrolled 548 ethnically diverse schoolchildren ( age 11.7 years , SD 0.8 ) from public schools in four Massachusetts communities , and studied them prospect ively for 19 months from October , 1995 , to May , 1997 . We examined the association between baseline and change in consumption of sugar-sweetened drinks ( the independent variables ) , and difference in measures of obesity , with linear and logistic regression analyses adjusted for potentially confounding variables and clustering of results within schools . FINDINGS For each additional serving of sugar-sweetened drink consumed , both body mass index ( BMI ) ( mean 0.24 kg/m2 ; 95 % CI 0.10 - 0.39 ; p=0.03 ) and frequency of obesity ( odds ratio 1.60 ; 95 % CI 1.14 - 2.24 ; p=0.02 ) increased after adjustment for anthropometric , demographic , dietary , and lifestyle variables . Baseline consumption of sugar-sweetened drinks was also independently associated with change in BMI ( mean 0.18 kg/m2 for each daily serving ; 95 % CI 0.09 - 0.27 ; p=0.02 ) . INTERPRETATION Consumption of sugar-sweetened drinks is associated with obesity in children Dietary compensation for energy provided as ethanol is reportedly limited . Whether this is a function of the ethanol or other aspect of the medium in which it is ingested is not known . Eight male and eight female adults ingested 1.08 liters of beer ( 5.0 % ethanol w/v , 1891kJ ) , light beer ( 2.9 % ethanol w/v , 1197kJ ) , no-alcohol beer ( 0.1 % ethanol w/v , 816kJ ) , cola ( 1749kJ ) or carbonated water ( 0kJ ) every 3 - 4 days with a midday meal . Diet records were kept the preceding day and day of beverage ingestion . Energy intake was significantly higher each day an energy-bearing beverage was consumed relative to its preceding day . A literature review revealed dietary compensation for modifications of energy intake via fluids is less precise than when solid foods are manipulated . These findings demonstrate dietary adjustment for energy derived from ethanol is imprecise , but also indicate energy from carbohydrate elicits little dietary response when ingested in a beverage Whereas soft drinks are described as primarily thirst-quenching liquids , juices and milk are said to be liquid foods , with a greater satiating power . This study was conducted to compare the effects of orange juice , low-fat milk ( 1 % ) , regular cola , and sparkling water on hunger , thirst , satiety , and energy intakes at the next meal . Thirty-two volunteers ( 14 men and 18 women ) , ages 18 - 35 years , consumed a breakfast preload composed of 590 ml ( 20 oz ) of an energy-containing beverage ( 1036 kJ ) or water ( 0 kJ ) and a slice of toast ( 418 kJ ) on four different occasions . Participants rated hunger , thirst , fullness , and desire to eat at baseline and at 20-min intervals for 2 h following preload ingestion . A tray lunch was presented at 2 h , 15 min and food consumption was measured . Compared to sparkling water , the three energy-containing beverages were associated with higher fullness and reduced hunger rating and desire to eat . However , energy intakes at lunch ( 4511+/-151 kJ for men and 3183+/-203 kJ for women ) were the same across all four beverage conditions and no compensation for breakfast energy was observed . The three beverages of equal energy value were significantly different from sparkling water , but not from each other , in their effects on hunger and satiety ratings . All four beverages satisfied thirst equally well . Whether energy-containing cola , juice , and low-fat milk facilitate a positive energy balance remains a topic for further study Objective The present study evaluated weight loss and compliance outcomes for overweight adolescents assigned to one of two dietary interventions differing in the type of snacks allowed . Methods The study was a 12-week , controlled clinical trial , among otherwise healthy but overweight ( body mass index ≥95th percentile ) 11-year-old to 15-year-old girls who were r and omly assigned to either a 1,500 kcal/day free-snack program or a 1,500 kcal/day restricted-snack program . All subjects were counseled to consume three servings of dairy products per day , and were provided with a 500 mg calcium supplement as well . Subjects in the free-snack group could choose any 150-calorie item as one of their two daily snacks , including regular soda if desired ; however , subjects in the restricted-snack group were limited to diet soda . Results Thirty-two adolescent girls completed the 12-week intervention . Both diets were equally effective in achieving a modest amount of weight loss , and were equally acceptable to the subjects . Significant decreases in weight , body mass index , anthropometric measures , total cholesterol and triglycerides were observed . Conclusions A 1,500 kcal/day diet allowing for a free snack of 150 calories was equally as effective as a more restricted snack policy in achieving a modest amount of weight loss among overweight 11-year-old to 15-year-old girls . In addition , results suggest that some soda may be included in a teen weight control diet , as long as caloric intake is maintained at recommended levels , and care is taken to achieve adequate intake of essential nutrients . Calcium intake among subjects was low at baseline , and , although it increased during the study ( due to supplementation ) , further efforts to increase consumption of naturally calcium-rich and calcium-fortified foods and beverages are needed BACKGROUND A population of over 12,000 mature subjects participated in a longitudinal study ( 8 years ) of nutrition and health ( the Su . Vi . Max Study ) . In this context , a specific cross-sectional study was carried out in a r and omly selected sub population . AIM To identify anthropometric , nutritional and biochemical correlates of spontaneous use of ' light ' foods and drinks in a free-living population . DESIGN Men ( n = 2299 ) and women ( n = 1979 ) , 45 - 60 years , reported their food intakes over six non-consecutive days . Consumers of low-fat and low-sugar foods and drinks , and artificial sweeteners , were compared with non-consumers . RESULTS Users of low-sugar products were heavier than non-users ; female consumers of low-fat products , but not males , had higher body weight and BMI than non-consumers . Users of low-sugar products had higher triacylglycerols and glycaemia than non-users while biochemical parameters were not different in users and non-users of low-fat products . Use of low-sugar products led to increased diet density of a few micronutrients , including cholesterol . Low-fat product selection was associated with increased intake of most micronutrients , both in absolute value and in density . CONCLUSIONS In mature adults , selection of fat-reduced products was associated with improved quality of the diet , while anthropometric and biological parameters appeared less favourable in consumers of low-sugar products vs. non-consumers . The longitudinal follow-up of the cohort in future years will help determine cause- and -effect relationships among these parameters OBJECTIVE To examine the secular trends in the association between obesity and hypertension among American adults between 1999 and 2014 . METHODS Data from the 1999 - 2014 National Health and Nutrition Examination Survey ( eight survey cycles ) were used . Obesity was determined from measured body mass index , with hypertension assessed from measured blood pressure and self-reported medication use . Meta-regression was used to examine the linear , quadratic , and cubic trends of the relationship between the observed odds ratio effect sizes ( obesity and hypertension ) and the NHANES cycles ( year ) using a r and om-effects model . RESULTS Across the years of 1999 to 2014 , there was a significant , positive linear trend ( p = .006 ) in the association between overweight/obesity and hypertension . CONCLUSION Our findings suggest that the association between overweight/obesity and hypertension is becoming stronger over time . Continued surveillance of temporal changes associated with obesity and hypertension is necessary to monitor how such changes may underlie changes in the risk for chronic disease . SIGNIFICANCE OF THE STUDY This novel study evaluates whether the magnitude of association between obesity and hypertension has changed over the last 15-years Importance Health care professionals commonly recommend increased water consumption , typically to 8 cups per day , as part of a weight-reducing diet . However , this recommendation is based on limited evidence and virtually no experimental data from the pediatric population . Objective To compare 2 st and ardized weight-loss diets among adolescents with overweight or obesity , either with or without additional advice and behavioral support to increase habitual water intake to 8 cups per day . Design , Setting , and Participants A r and omized clinical , parallel-group trial was conducted between February 2 , 2011 , and June 26 , 2014 , at Boston Children ’s Hospital , Boston , Massachusetts , among 38 adolescents with overweight or obesity who reported drinking 4 cups or less of water per day . Interventions All participants in both groups received similar weight-reducing interventions , differentiated by advice about water intake ( the water group received advice to increase water intake to 8 cups per day ; the control group did not receive such advice ) but controlled for other dietary recommendations and treatment intensity . The interventions included dietary counseling , daily text messages , and a cookbook with health guides . To support adherence to 8 cups of water per day , the water group received well-defined messages about water through counseling and daily text messages , a water bottle , and a water pitcher with filters . Main Outcomes and Measures The primary outcome was 6-month change in body mass index z score . Data analyses followed the intention-to-treat principle . Results All 38 participants ( 27 girls and 11 boys ; mean [ SD ] age , 14.9 [ 1.7 ] years ) completed the study . Both groups reported drinking approximately 2 cups of water per day at baseline . Self-reported change in water intake at 6 months was greater in the water group ( difference from baseline , 2.8 cups per day [ 95 % CI , 1.8 to 3.8 ] ; P < .001 ) compared with that in the control group ( difference from baseline , 1.2 cups per day [ 95 % CI , 0.2 to 2.2 ] ; P = .02 ) ( difference between groups , 1.6 cups per day [ 95 % CI , 0.2 to 3.0 cups per day ] ; P = .03 ) . The 6-month change in body mass index z score did not differ between the water group ( difference from baseline , –0.1 [ 95 % CI , –0.2 to –0.0 ] ; P = .005 ) and the control group ( difference from baseline , –0.1 [ 95 % CI , –0.2 to –0.0 ] ; P = .008 ) ( difference between groups , –0.0 [ 95 % CI , −0.1 to 0.1 ] ; P = .88 ) . Conclusions and Relevance Advice and behavioral supports to consume 8 cups of water per day in the context of a weight-reducing diet did not affect body weight among adolescents with overweight or obesity . Despite intensive behavior supports , few adolescents achieved the target of 8 cups of water per day . Environmental interventions to reduce barriers to water consumption at school may be necessary in future research of the feasibility and effectiveness to achieve the target of an intake of 8 cups of water per day in adolescents . Trial Registration clinical trials.gov Identifier : OBJECTIVE To investigate the efficacy of water preloading before meals as a weight loss strategy for adults with obesity Output:	The most effective intervention among the studies was the replacement of caloric beverages with water . In conclusion , despite 5.15 % of weight loss , the low to moderate quality of evidence and the short term of follow-up are limitations to support evidence -based recommendations of water consumption for weight loss
MS22178	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background : The effect of regular and expected printed educational material s on physician prescribing behaviour has not been studied . We sought to measure the impact of a series of evidence -based drug therapy letters mailed to physicians in British Columbia on prescribing to newly treated patients . Methods : A paired , cluster r and omized community design was used . The study population included 499 physicians from 24 local health areas in British Columbia . Local health areas were paired by number of physicians , and 1 of each pair was r and omly selected and its physicians assigned to an intervention group or a control group . The intervention was 12 issues of an evidence -based series called Therapeutics Letter . Physicians in the control group ( n = 241 ) received the letters 3–8 months after physicians in the intervention group ( n = 258 ) . The impact on prescribing to newly treated patients ( defined as patients who had not previously made a cl aim for any medication from the class of drugs profiled in the letter ) was analyzed using the drug cl aims data base of BC Pharmacare , a publicly funded drug benefits program that covered all seniors and people receiving social assistance . Results : The probability of prescribing a drug recommended in the Therapeutics Letter rather than another drug in the same class increased by 30 % in the 3 months after the mailing of the letter relative to the preceding 3 months , adjusted for any before – after changes in the control group ( relative risk 1.30 ; 95 % confidence interval 1.13–1.52 ) . No letter achieved statistical significance on its own . However , 11 of the 12 letters produced prescribing changes in the predicted direction such that the overall result was significant when their effect was combined . Interpretation : The combined effect of an ongoing series of printed letters distributed from a credible and trusted source can have a clinical ly significant effect on prescribing to newly treated patients Background R and omised controlled trials of implementation strategies tell us whether ( or not ) an intervention results in changes in professional behaviour but little about the causal mechanisms that produce any change . Theory-based process evaluations collect data on theoretical constructs alongside r and omised trials to explore possible causal mechanisms and effect modifiers . This is similar to measuring intermediate endpoints in clinical trials to further underst and the biological basis of any observed effects ( for example , measuring lipid profiles alongside trials of lipid lowering drugs where the primary endpoint could be reduction in vascular related deaths).This study protocol describes a theory-based process evaluation alongside the Ontario Printed Educational Message ( OPEM ) trial . We hypothesize that the OPEM interventions are most likely to operate through changes in physicians ' behavioural intentions due to improved attitudes or subjective norms with little or no change in perceived behavioural control . We will test this hypothesis using a well-vali date d social cognition model , the theory of planned behaviour ( TPB ) that incorporates these constructs . Methods / design We will develop theory-based surveys using st and ard methods based upon the TPB for the second and third replications , and survey a sub sample of Ontario family physicians from each arm of the trial two months before and six months after the dissemination of the index edition of informed , the evidence based newsletter used for the interventions . In the third replication , our study will converge with the " TRY-ME " protocol ( a second study conducted alongside the OPEM trial ) , in which the content of educational messages was constructed using both st and ard methods and methods informed by psychological theory . We will modify Dillman 's total design method to maximise response rates . Preliminary analyses will initially assess the internal reliability of the measures and use regression to explore the relationships between predictor and dependent variable ( intention to advise diabetic patients to have annual retinopathy screening and to prescribe thiazide diuretics for first line treatment of uncomplicated hypertension ) . We will then compare groups using methods appropriate for comparing independent sample s to determine whether there have been changes in the predicted constructs ( attitudes , subjective norms , or intentions ) across the study groups as hypothesised , and will assess the convergence between the process evaluation results and the main trial results .Trial registration numberCurrent controlled trial IS RCT OBJECTIVES To assess the feasibility of a multifaceted strategy to translate evidence -based guidelines for treating nursing home-acquired pneumonia ( NHAP ) into practice using a small intervention trial . DESIGN Pre-posttest with untreated control group . SETTING Two Colorado State Veterans Homes ( SVHs ) during two influenza seasons . PARTICIPANTS Eighty-six residents with two or more signs of lower respiratory tract infection . INTERVENTION Multifaceted , including a formative phase to modify the intervention , institutional-level change emphasizing immunization , and availability of appropriate antibiotics ; interactive educational sessions for nurses ; and academic detailing . MEASUREMENTS Subjects ' SVH medical records were review ed for guideline compliance retrospectively for the influenza season before the intervention and prospect ively during the intervention . Bivariate comparisons-of-care processes between the intervention and control facility before and after the intervention were made using the Fischer exact test . RESULTS At the intervention facility , compliance with five of the guidelines improved : influenza vaccination , timely physician response to illness onset , x-ray for patients not being hospitalized , use of appropriate antibiotics , and timely antibiotic initiation for unstable patients . Chest x-ray and appropriate and timely antibiotics were significantly better at the intervention than at the control facility during the intervention year but not during the control year . CONCLUSION Multifaceted , evidence -based , NHAP guideline implementation improved care processes in a SVH . Guideline implementation should be studied in a national sample of nursing homes to determine whether it improves quality of life and functional outcomes of this debilitating illness for long-term care residents OBJECTIVES . To determine whether we could increase adherence to the Centers for Disease Control and Prevention ( CDC ) recommendations with well-accepted approaches to improving quality of care and adherence to the CDC recommendations result ed in improved outcomes for acute otitis media ( AOM ) . METHODS . A cluster r and omization study was conducted in 12 pediatric practice s ( 6 intervention and 6 control sites ) . The main outcome measures were adherence to the CDC recommendations ( modified to include 2 additional antimicrobial agents ) and a subsequent antibiotic prescription for AOM within 30 days after diagnosis . RESULTS . Of 3152 patients referred to research assistants , 2584 ( 82 % ) were eligible . Of those eligible , 1368 ( 99 % ) of 1382 at the intervention sites and 1138 ( 99 % ) of 1146 at the control sites consented to participate . Rates of adherence to the CDC recommendations were not significantly higher at the intervention sites than at the control sites , for initial enrollment episodes ( 78.2 % vs 70.6 % ) or second episodes ( 62.6 % vs 59.9 % ) . After controlling for clustering according to site and covariates , children who were not treated in adherence to the CDC recommendations for both episodes had 1.60 times the odds of a subsequent prescription within 12 days , compared with those treated in adherence at both episodes . CONCLUSIONS . Despite using evidence -based approaches that are known to influence physician behavior , we were unable to increase adherence to the CDC recommendations for treatment of AOM . However , we did establish that prescription of antimicrobial therapy consistent with the CDC recommendations for a second episode of AOM was associated with improved outcomes , measured as the need for subsequent antibiotic prescription . Because of the selection of resistant otopathogens , adherence to the CDC recommendations is likely more important in subsequent episodes of AOM than in the initial episode Objectives : To evaluate the impact of using pain assessment scales on the management of musculoskeletal chronic pain . Methods : Cluster-r and omized controlled multicentre trial in French general practice setting s. Practice s were r and omized by region before patient recruitment . The inclusion concerned patients suffering from musculoskeletal chronic pain . General practitioners assigned to the scale group used two vali date d assessment instruments ; those assigned to the control group cared for their patients according to their usual practice . The primary end-point was the level of relief obtained and the secondary changes in prescription of painkilling modalities . Results : A total of 155 general practitioners included 772 successive patients suffering from musculoskeletal chronic pain . The control group reported a mean level of relief of 50.7 % compared with one of 41.1 % in the scale group ( p<0.0001 ) . In the intervention group , physicians decreased significantly their prescription of level two painkillers . Conclusions . In general practice , the use of pain assessment scales is not associated with greater pain relief . The lesser level of pain relief obtained in the scale group does provide evidence that using pain assessment scales does not enhance the relief of chronic pain in patients in primary care . Guidelines which recommend the systematic use of scales for the assessment and monitoring of chronic pain are not tailored to either the context or the patients encountered in the primary care setting Background A challenge for implementation research ers is to develop principles that could generate testable hypotheses that apply across a range of clinical context s , thus leading to generalisability of findings . Such principles may be provided by systematic ally developed theories . The opportunity has arisen to test some of these theoretical principles in the Ontario Printed Educational Material s ( OPEM ) trial by conducting a sub-trial within the existing trial structure . OPEM is a large factorial cluster-r and omised trial evaluating the effects of short directive and long discursive educational messages embedded into informed , an evidence -based newsletter produced in Canada by the Institute for Clinical Evaluative Sciences ( ICES ) and mailed to all primary care physicians in Ontario . The content of educational messages in the sub-trial will be constructed using both st and ard methods and methods inspired by psychological theory . The aim of this study is to test the effectiveness of the TheoRY-inspired MEssage ( ' TRY-ME ' ) compared with the ' st and ard ' message in changing prescribing behaviour . Methods The OPEM trial participants r and omised to receive the short directive message attached to the outside of informed(an ' outsert ' ) will be sub-r and omised to receive either a st and ard message or a message informed by the theory of planned behaviour ( TPB ) using a two ( long insert or no insert ) by three ( theory-based outsert or st and ard outsert or no outsert ) design . The messages will relate to prescription of thiazide diuretics as first line drug treatment for hypertension ( described in the accompanying protocol , " The Ontario Printed Educational Material s trial " ) . The short messages will be developed independently by two research teams . The primary outcome is prescription of thiazide diuretics , measured by routinely collected data available within ICES . The study is design ed to answer the question , is there any difference in guideline adherence ( i.e. , thiazide prescription rates ) between physicians in the six groups ? A process evaluation survey instrument based on the TPB will be administered pre- and post-intervention ( described in the accompanying protocol , " Looking inside the black box " ) . The second research question concerns processes that may underlie observed differences in prescribing behaviour . We expect that effects of the messages on prescribing behaviour will be mediated through changes in physicians ' cognitions . Trial registration numberCurrent controlled trial IS RCT Background Psychological models can be used to underst and and predict behaviour in a wide range of setting s. However , they have not been consistently applied to health professional behaviours , and the contribution of differing theories is not clear . The aim of this study was to explore the usefulness of a range of psychological theories to predict health professional behaviour relating to management of upper respiratory tract infections ( URTIs ) without antibiotics . Methods Psychological measures were collected by postal question naire survey from a r and om sample of general practitioners ( GPs ) in Scotl and . The outcome measures were clinical behaviour ( using antibiotic prescription rates as a proxy indicator ) , behavioural simulation ( scenario-based decisions to managing URTI with or without antibiotics ) and behavioural intention ( general intention to managing URTI without antibiotics ) . Explanatory variables were the constructs within the following theories : Theory of Planned Behaviour ( TPB ) , Social Cognitive Theory ( SCT ) , Common Sense Self-Regulation Model ( CS-SRM ) , Operant Learning Theory ( OLT ) , Implementation Intention ( II ) , Stage Model ( SM ) , and knowledge ( a non-theoretical construct ) . For each outcome measure , multiple regression analysis was used to examine the predictive value of each theoretical model individually . Following this ' theory level ' analysis , a ' cross theory ' analysis was conducted to investigate the combined predictive value of all significant individual constructs across theories . Results All theories were tested , but only significant results are presented . When predicting behaviour , at the theory level , OLT explained 6 % of the variance and , in a cross theory analysis , OLT ' evidence of habitual behaviour ' also explained 6 % . When predicting behavioural simulation , at the theory level , the proportion of variance explained was : TPB , 31 % ; SCT , 26 % ; II , 6 % ; OLT , 24 % . GPs who reported having already decided to change their management to try to avoid the use of antibiotics made significantly fewer scenario-based decisions to prescribe . In the cross theory analysis , perceived behavioural control ( TPB ) , evidence of habitual behaviour ( OLT ) , CS-SRM cause ( chance/bad luck ) , and intention entered the equation , together explaining 36 % of the variance . When predicting intention , at the theory level , the proportion of variance explained was : TPB , 30 % ; SCT , 29 % ; CS-SRM 27 % ; OLT , 43 % . GPs who reported that they had already decided to change their management to try to avoid the use of antibiotics had a significantly higher intention to manage URTIs without prescribing antibiotics . In the cross theory analysis , OLT evidence of habitual behaviour , TPB attitudes , risk perception , CS-SRM control by doctor , TPB perceived behavioural control and CS-SRM control by treatment entered the equation , together explaining 49 % Output:	Audit and feedback , together with educational outreach visits , were the focus of the majority of recent , high- quality research into prescribing interventions . These interventions were also the most effective in improving prescribing practice . There is insufficient recent research into manual reminders to confidently up date earlier review s and there remains insufficient evidence to draw conclusions regarding the effectiveness of local consensus processes or multidisciplinary teams . Conclusions : Educational outreach as well as audit and feedback continue to dominate research into prescribing interventions . These 2 prescribing interventions also most consistently show positive results .
MS22179	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Palliative care planning for nursing home residents with advanced dementia is often suboptimal . This study compared effects of facilitated case conferencing ( FCC ) with usual care ( UC ) on end-of-life care . Methods A two arm parallel cluster r and omised controlled trial was conducted . The sample included people with advanced dementia from 20 Australian nursing homes and their families and professional caregivers . In each intervention nursing home ( n = 10 ) , Palliative Care Planning Coordinators ( PCPCs ) facilitated family case conferences and trained staff in person-centred palliative care for 16 hours per week over 18 months . The primary outcome was family-rated quality of end-of-life care ( End-of-Life Dementia [ EOLD ] Scales ) . Secondary outcomes included nurse-rated EOLD scales , resident quality of life ( Quality of Life in Late-stage Dementia [ QUALID ] ) and quality of care over the last month of life ( pharmacological/non-pharmacological palliative strategies , hospitalization or inappropriate interventions ) . Results Two-hundred-eighty-six people with advanced dementia took part but only 131 died ( 64 in UC and 67 in FCC which was fewer than anticipated ) , rendering the primary analysis under-powered with no group effect seen in EOLD scales . Significant differences in pharmacological ( P < 0.01 ) and non-pharmacological ( P < 0.05 ) palliative management in last month of life were seen . Intercurrent illness was associated with lower family-rated EOLD Satisfaction with Care ( coefficient 2.97 , P < 0.05 ) and lower staff-rated EOLD Comfort Assessment with Dying ( coefficient 4.37 , P < 0.01 ) . Per protocol analyses showed positive relationships between EOLD and staff hours to bed ratios , proportion of residents with dementia and staff attitudes . Conclusion FCC facilitates a palliative approach to care . Future trials of case conferencing should consider outcomes and processes regarding decision making and planning for anticipated events and acute illness . Trial registration Australian New Zeal and Clinical Trial Registry PURPOSE OF STUDY Dementia affects more than 5 million Americans , and is a leading cause of death . Family members of nursing home ( NH ) residents with advanced dementia report difficulty making decisions about care toward the end of life . As part of a r and omized trial testing an intervention to improve decision making , this qualitative study aim ed to underst and how family decision makers experienced goal -based decision making in advance of the death of their relative . DESIGN AND METHODS This qualitative study was conducted as part of the goals of care clinical trial . Study participants ( n = 16 ) were family decision makers in North Carolina whose relative with advanced dementia died after participating in the goals of care intervention . Semi-structured interviews were analyzed using a qualitative description approach . RESULTS Family members ' experience of decision making and death differed based on the presence or absence of trusting relationships with NH staff . Family members who reported trust described a positive end-of-life experience and less need for prescribed goals of care discussion s. In the absence of trust , family members reported that goals of care discussion s were ignored by staff or created confusion . IMPLICATION S Among family members of persons who recently died from dementia in NHs , expressions of trust in staff were strongly related to perceptions of decision making about goals of care . Although goals of care discussion s may potentially promote communication to earn trust , the presence of pre-existing trust ultimately influenced the decision making and end-of-life experiences of residents and families Background : In dementia care , a large number of treatment decisions are made by family carers on behalf of their family member who lacks decisional capacity ; advance care planning can support such carers in the decision-making of care goals . However , given the relative importance of advance care planning in dementia care , the prevalence of advance care planning in dementia care is poor . Aim : To evaluate the effectiveness of advance care planning with family carers in dementia care homes . Design : Paired cluster r and omized controlled trial . The intervention comprised a trained facilitator , family education , family meetings , documentation of advance care planning decisions and intervention orientation for general practitioners and nursing home staff . Setting / participants : A total of 24 nursing homes with a dementia nursing category located in Northern Irel and , United Kingdom . Family carers of nursing home residents classified as having dementia and judged as not having decisional capacity to participate in advance care planning discussion s. Results : The primary outcome was family carer uncertainty in decision-making about the care of the resident ( Decisional Conflict Scale ) . There was evidence of a reduction in total Decisional Conflict Scale score in the intervention group compared with the usual care group ( −10.5 , 95 % confidence interval : −16.4 to −4.7 ; p < 0.001 ) . Conclusion : Advance care planning was effective in reducing family carer uncertainty in decision-making concerning the care of their family member and improving perceptions of quality of care in nursing homes . Given the global significance of dementia , the implication s for clinicians and policy makers include them recognizing the importance of family carer education and improving communication between family carers and formal care providers Background : Increasing number of people are dying with advanced dementia . Comfort and quality of life are key goals of care . Aims : To describe ( 1 ) physical and psychological symptoms , ( 2 ) health and social care service utilisation and ( 3 ) care at end of life in people with advanced dementia . Design : 9-month prospect i ve cohort study . Setting and participants : Greater London , Engl and , people with advanced dementia ( Functional Assessment Staging Scale 6e and above ) from 14 nursing homes or their own homes . Main outcome measures : At study entry and monthly : prescriptions , Charlson Comorbidity Index , pressure sore risk/severity ( Waterlow Scale/Stirling Scale , respectively ) , acute medical events , pain ( Pain Assessment in Advanced Dementia ) , neuropsychiatric symptoms ( Neuropsychiatric Inventory ) , quality of life ( Quality of Life in Late-Stage Dementia Scale ) , re source use ( Re source Utilization in Dementia Question naire and Client Services Receipt Inventory ) , presence/type of advance care plans , interventions , mortality , place of death and comfort ( Symptom Management at End of Life in Dementia Scale ) . Results : Of 159 potential participants , 85 were recruited ( 62 % alive at end of follow-up ) . Pain ( 11 % at rest , 61 % on movement ) and significant agitation ( 54 % ) were common and persistent . Aspiration , dyspnoea , septicaemia and pneumonia were more frequent in those who died . In total , 76 % had ‘ do not resuscitate ’ statements , less than 40 % advance care plans . Most received primary care visits , there was little input from geriatrics or mental health but contact with emergency paramedics was common . Conclusion : People with advanced dementia lived with distressing symptoms . Service provision was not tailored to their needs . Longitudinal multidisciplinary input could optimise symptom control and quality of life Background : Despite increased attention for palliative care in dementia , recent studies found burdensome symptoms and unmet family caregiver needs in the last phase of life . Feedback is being used to improve the quality of palliative care , but we do not know how effective it is . Aim : To assess the effect of two feedback strategies on perceived quality of end-of-life care and comfort in dying nursing home residents with dementia . Methods : In a cluster-r and omized controlled trial , the End-of-Life in Dementia – Satisfaction With Care and the End-of-Life in Dementia – Comfort Assessment in Dying scales were completed by bereaved family caregivers of residents with dementia of 18 Dutch nursing homes . Two feedback strategies , generic feedback with mean End-of-Life in Dementia-scores and feedback with individual ( patient-specific ) End-of-Life in Dementia-scores , were compared to no feedback provided . The intervention groups discussed End-of-Life in Dementia-ratings in team meetings and formulated actions to improve care . Multi-level analyses assessed effects . Results : A total of 668 families rated the End-of-Life in Dementia – instruments . Compared to no feedback , the generic strategy result ed in lower quality of end-of-life care in unadjusted ( B = −1.65 , confidence interval = −3.27 ; −0.21 ) and adjusted analyses ( B = −2.41 , confidence interval = −4.07 ; −0.76 ) , while there was no effect on comfort . The patient-specific strategy did not affect the quality of end-of-life care , but it increased comfort in unadjusted analyses ( only , B = 2.20 , confidence interval = 0.15 ; 4.39 ; adjusted : B = 1.88 , confidence interval = −0.34 ; 4.10 ) . Conclusion : Neither feedback strategy improved end-of-life outcome . Perhaps , skills to translate the feedback into care improvement actions were insufficient . Feedback with favorable family ratings might even have triggered opposite effects . Trial number : NTR3942 BACKGROUND Increasing numbers of older people with advanced dementia are cared for in care homes . No cure is available , so research focused on improving quality of life and quality of care for people with dementia is needed to support them to live and die well . The Namaste Care programme is a multi-dimensional care program with sensory , psycho-social and spiritual components intended to enhance quality of life and quality of care for people with advanced dementia . The aim of the study was to establish whether the Namaste Care program can be implemented in UK care homes ; and what effect Namaste Care has on the quality of life of residents with advanced dementia , their families and staff . This article explores the qualitative findings of the study , reporting the effect of the programme on the families of people with advanced dementia and care home staff , and presenting their perceptions of change in care . METHODS An organisational action research methodology was used . Focus groups and interviews were undertaken pre/post implementation of the Namaste Care program . The research er kept a reflective diary recording data on the process of change . A comments book was available to staff and relatives in each care home . Data was analysed thematically within each care home and then across all care homes . RESULTS Six care homes were recruited in south London : one withdrew before the study was underway . Of the five remaining care homes , four achieved a full Namaste Care program . One care home did not achieve the full program during the study , and another discontinued Namaste Care when the study ended . Every home experienced management disruption during the study . Namaste Care challenged normal routinised care for older people with advanced dementia . The characteristics of care uncovered before Namaste was implemented were : chaos and confusion , rushing around , lack of trust , and rewarding care . After the programme was implemented these perceptions were transformed , and themes of calmness , reaching out to each other , seeing the person , and , enhanced well-being , emerged . CONCLUSIONS Namaste Care can enrich the quality of life of older people with advanced dementia in care homes . The program was welcomed by care home staff and families , and was achieved with only modest expenditure and no change in staffing levels . The positive impact on residents quality of life influenced the well-being of family carers . Care staff found the changes in care enjoyable and rewarding . Namaste Care was valued for the benefits seen in residents ; the improvement in relationships ; and the shift towards a person-centred , relationship-based culture of care brought about by introducing the program . Namaste Care deserves further exploration and investigation including a r and omised controlled trial People with dementia have often been excluded from pain studies . However , there is evidence supporting that people with dementia experience frequent pain , often poorly assessed and undertreated , and that the etiology for pain descriptions is poorly documented . The Assessment of Discomfort in Dementia ( ADD ) Protocol is design ed to : a ) more accurately assess discomfort in people with dementia who can no longer verbally describe physical pain or affective discomfort ; b ) more accurately and thoroughly treat physical pain and affective discomfort ; and c ) decrease inappropriate use of psychotropic medication . The use of the ADD Protocol was studies with a convenience sample of 104 residents of long-term care with end-stage dementia . Use of the ADD Protocol was associated with a significant decrease in discomfort ( t = 6.56 , p = 0.000 ) . The most frequently seen behavioral symptoms associated with discomfort were tense body language , sad facial expression , fidgeting , perseverant verbalizations , and verbal outburts . The ADD Protocol was also associated with a significant increase in the use of scheduled analgesics and non-pharmacological comfort interventions . The protocol was not associated with an increase in the use of prn analgesics or with prn or scheduled psychotropics . This study has provided some support for the notion that the needs of people with significant dementia can be discerned and treated OBJECTIVES To test whether a decision aid improves quality of decision-making about feeding options in advanced dementia . DESIGN Cluster r and omized controlled trial . SETTING Twenty-four nursing homes in North Carolina . PARTICIPANTS Residents with advanced dementia and feeding problems and their surrogates . INTERVENTION Intervention surrogates received an audio or print decision aid on feeding options in advanced dementia . Controls received usual care . MEASUREMENTS Primary outcome was the Decisional Conflict Scale ( range : 1 - 5 ) measured at 3 months ; other main outcomes were surrogate knowledge , frequency of communication with providers , and feeding treatment use . RESULTS Two hundred fifty-six residents and surrogate decision-makers were recruited . Residents ' average age was 85 ; 67 % were Caucasian , and 79 % were women . Surrogates ' average age was 59 ; 67 % were Caucasian , and 70 % were residents ' children . The intervention improved knowledge scores ( 16.8 vs 1 Output:	Conclusion : Almost all domains were addressed across all interventions currently offered for this population to various degrees , but not within a singular intervention .
MS22180	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND The diagnosis and treatment of chronic hepatitis C are major concerns in prisons . OBJECTIVES The aim of this r and omized clinical trial was to determine the extent to which directly observed therapy ( DOT ) improved the efficacy of the st and ard treatment for chronic hepatitis C in the prison setting . PATIENTS AND METHODS A r and omized clinical trial was carried out to evaluate the efficacy of a DOT compared with a self-administered therapy in prison inmates who underwent st and ard treatment for chronic hepatitis C ( based on pegylated interferon alpha-2a and ribavirin ) . RESULTS A total of 252 inmates were r and omized , of which 244 were analyzed : 109 in the DOT group and 135 in the non-DOT group . The mean age was 35.88 years ( SD 6.54 ) , 94.3 % were men , 72.1 % reported intravenous drug use , 21.3 % were HIV co-infected , and 55.3 % had genotype 1 or 4 . The patients received the study treatment for a median time of 33.9 weeks in the overall sample . Sustained virological response was achieved in 60.6 % ( 95 % CI , 51.17 - 69.22 ) of the DOT group and in 65.9 % ( 95 % CI , 57.59 - 73.38 ) of the st and ard therapy group ( risk ratio=0.92 ; 95 % CI , 0.76 - 1.12 ) . The mean proportion of patients continuing the treatment was 83 % ( SD=31 ) . Adverse events were reported in 93.4 % of the patients , and serious adverse events were reported in 8.2 % , with no significant differences between groups . CONCLUSIONS Sustained virological response was remarkably high , although there were no differences between groups , probably due to high treatment adherence Introduction People who inject drugs represent an under-treated chronic hepatitis C virus (HCV)-infected patient population . Methods INTEGRATE was a prospect i ve , observational study investigating the effectiveness , safety , and adherence in routine clinical practice to telaprevir in combination with peg-interferon and ribavirin ( Peg-IFN/RBV ) in patients with history of injecting drug use chronically infected with genotype 1 HCV . Results A total of 46 patients were enrolled and included in the intent-to-treat ( ITT ) population . Among heroin and /or cocaine users ( n = 37 ; 80 % ) , 22 % reported use in the past month ; 74 % ( 34/46 ) of patients were on opioid substitution therapy in the pre-treatment phase , and 43 % ( 20/46 ) discontinued HCV treatment prematurely . Sustained virologic response rate was 54 % ( 25/46 ) in the ITT population and 74 % ( 25/34 ) in the per protocol ( evaluable-for-effectiveness ) population . The main reason for failure in the ITT analysis was loss to follow-up ( n = 8 ; 17 % ) . Adverse events occurred in 91 % ( 42/46 ) of patients . Mean patient-reported adherence to study drugs was > 89 % at Week 4 , Week 12 and end of treatment . Conclusion Despite a high rate of treatment discontinuation ( including loss to follow-up ) , self-reported adherence to treatment was good and virologic cure rates were similar to those reported in large real-world cohorts . Our findings suggest that people with a history of injecting drug use should be considered for treatment of chronic HCV infection , and highlight the need for improvements in patient support to boost retention in care and , in turn , help to prevent reinfection and transmission . Clinical trial registration Clinical trials.gov identifier , NCT01980290 . Funding Janssen Pharmaceuticals Background : Hepatitis C virus ( HCV ) is a prevalent chronic blood-borne infection among opioid-dependent patients on methadone maintenance treatment ( MMT ) . Despite case reports and case – control studies , a r and omized controlled trial ( RCT ) examining HCV treatment adherence in methadone-maintained patients is lacking and was the impetus for this ongoing RCT examining modified directly administered therapy for HCV treatment integrated within a MMT . Methods : Subjects were r and omized 1:1 to receive HCV treatment as modified directly observed therapy ( mDOT ) into the MMT program or at a liver specialty clinic as self-administered therapy ( SAT ) . R and omization was stratified based on HIV status and HCV genotype . Results : Twenty-one subjects to date have enrolled in this pilot study . The mDOT subjects have had greater success in starting treatment and 10 of the 12 mDOT subjects achieved early virologic response ( EVR ) at week 12 and 6 of those 10 achieved sustained virologic response ( SVR ) . Of the nine SAT subjects , only three achieved EVR at week 12 and only one achieved SVR despite not completing the treatment . Conclusions : Hepatitis C treatment can be successfully integrated into a methadone maintenance clinic , and mDOT can be implemented with a methadone clinic ’s existing nursing and medical staff . Patients struggling with concurrent substance use and mental illness comorbidity may be successfully addressed in such setting s and facilitate access to and completion of treatment through the utilization of on-site clinical services for HCV treatment and adherence support with mDOT . The exact importance of site of services and adherence support remains a significant area for future investigation BACKGROUND This study investigated the efficacy and safety of directly observed pegylated interferon ( peg-IFN ) alfa-2a plus self-administered ribavirin ( RBV ) for the treatment of hepatitis C virus ( HCV ) among people with active drug use . METHODS A r and omized , open-label , parallel group trial of immediate vs delayed treatment with peg-IFN alfa-2a plus RBV in participants with recent injection drug and /or crack cocaine use ( prior 3 months ) . The primary end point was sustained virologic response ( SVR ) . RESULTS Sixty-six participants were r and omized ( immediate treatment , n = 48 ; delayed treatment , n = 18 ) . Loss to follow-up was comparable among those r and omized to immediate and delayed treatment ( 23 % vs 33 % , P = .389 ) . In a post hoc intent-to-treat analysis of all r and omized individuals , the SVR was 65 % ( 95 % confidence interval [ CI ] , 49%-78 % ; 31/48 ) in those r and omized to immediate treatment as compared to 39 % ( 95 % CI , 17%-64 % ; 7/18 ) in those r and omized to delayed treatment ( P = .060 ) . Among those who received delayed treatment ( 12/18 ) , SVR was 58 % ( 7/12 ) . Among 60 participants who received at least 1 dose of study medication , SVR was 63 % ( 95 % CI , 50%-75 % , n = 38 ) . Recent drug use at baseline ( past month ) did not impact completion or SVR . Discontinuation due to adverse events occurred in 7 % . The HCV reinfection rate was 2.8 per 100 person-years ( 95 % CI , 0.0 - 14.5 person-years ) with 1 reinfection observed among 23 remaining in follow-up post-SVR ( median , 1.8 years ; range , 0.5 - 1.8 years ) . CONCLUSIONS Among people actively using drugs treated with directly observed peg-IFN alfa-2a plus self-administered RBV , SVR is comparable to that seen in clinical trials of non-drug users , and the rate of HCV reinfection is low Non-r and omised studies of the effects of interventions are critical to many areas of healthcare evaluation , but their results may be biased . It is therefore important to underst and and appraise their strengths and weaknesses . We developed ROBINS-I ( “ Risk Of Bias In Non-r and omised Studies - of Interventions ” ) , a new tool for evaluating risk of bias in estimates of the comparative effectiveness ( harm or benefit ) of interventions from studies that did not use r and omisation to allocate units ( individuals or clusters of individuals ) to comparison groups . The tool will be particularly useful to those undertaking systematic review s that include non-r and omised studies BACKGROUND Direct-acting antiviral therapy ( DAAs ) for hepatitis C infection ( HCV ) have a much smaller burden of treatment than interferon-based regimes , require less monitoring and are very effective . New pathways are required to increase access to treatment amongst people prescribed opioid substitution therapy ( OST ) . METHODS An exploratory cluster r and omised controlled trial with mixed methods evaluation was undertaken to compare the uptake of dried blood spot testing ( DBST ) and treatment of people with genotype 1 HCV infection in a conventional service pathway versus a pharmacist-led pathway in a population receiving OST . RESULTS Pharmacies r and omised to the conventional pathway obtained 58 DBST from 244 patients (24%):15 new reactive tests and 33 new negative tests were identified . Within the pharmacist-led pathway , 94 DBST were obtained from 262 patients ( 36 % ) : 26 new reactive tests and 54 new negative tests were identified . Participants in the pharmacist-led pathway were more likely to take a DBST ( p<0.003 ) . Of participants referred for treatment through the conventional pathway , 4 patients from 15 with new reactive tests ( 27 % ) attended clinic for assessment . In the pharmacist-led treatment pathway , 20 patients from 26 with new reactive tests ( 77 % ) attended for assessment blood tests . Participants in the pharmacist-led pathway were more likely to proceed through the assessment for treatment ( p<0.002 ) . One participant completed treatment through the conventional pathway and three patients completed treatment through the pharmacist-led pathway . The process evaluation identified key themes important to service user completers and staff participants . CONCLUSION The study provides evidence that testing and treatment for HCV in a pharmacist led-pathway is a feasible treatment pathway for people who receive supervised OST consumption through community pharmacies . This feasibility trial therefore provides sufficient confirmation to justify proceeding to a full trial BACKGROUND : Adherence to chronic hepatitis C ( CHC ) treatment may be particularly challenging in methadone maintenance patients . We assessed the safety , tolerability , and efficacy of peginterferon alfa-2a/ribavirin treatment in methadone maintenance patients previously untreated for CHC . METHODS : Patients were r and omized 1:1 to direct observed therapy ( DOT ) or self-administration ( SA ) of peginterferon alfa-2a . DOT patients were seen weekly at methadone clinics ; SA patients were seen less frequently , only at investigative sites . Genotype 1-infected patients were treated for 48 wk with peginterferon alfa-2a ( 180 μg/wk)/ribavirin ( 1,000/1,200 mg/day ) ; genotypes 2- and 3-infected patients were treated for 24 wk with peginterferon alfa-2a ( 180 μg/wk)/ribavirin ( 800 mg/day ) . RESULTS : Based on defined efficacy stopping rules , 77 % ( 37/48 ) completed their targeted length of treatment , and 44 % ( 21/48 ) achieved sustained virologic response ( SVR ) . Two DOT and 3 SA patients were withdrawn for safety reasons and 6 and 9 , respectively , for nonsafety reasons . Over 60 % and 50 % of each group were > 80 % compliant with the planned cumulative doses of peginterferon alfa-2a and ribavirin , respectively , and over 60 % with overall treatment duration . SVR rates were 54 % ( 13/24 ) for DOT and 33 % ( 8/24 ) for SA ; 23 % ( 3/13 ) and 38 % ( 6/16 ) , respectively , for genotype 1 and 91 % ( 10/11 ) and 25 % ( 2/8 ) , respectively , for genotypes 2 and 3 . Stepwise logistic regression analysis , showed that DOT ( vs SA ; OR 3.27 , 95 % CI 0.90–11.91 , P= 0.073 ) and Caucasian race ( vs Other ; OR 13.31 , 95 % CI 1.42–124.71 , P= 0.023 ) were predictors of SVR . CONCLUSION : Peginterferon alfa-2a/ribavirin can be used safely and successfully in CHC patients receiving methadone maintenance OBJECTIVES To revise 2010 guidance on grading the strength of evidence ( SOE ) of the effectiveness of drugs , devices , and other preventive and therapeutic interventions in systematic review s produced by the Evidence -based Practice Center ( EPC ) program , established by the US Agency for Healthcare Research and Quality ( AHRQ ) . STUDY DESIGN AND SETTING A cross-EPC working group review ed authoritative systems for grading SOE [ primarily the approach from the Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) working group ] and conducted extensive discussion s with G Output:	Conclusion : Among people who use drugs , directly observed therapy may lead to higher odds of attaining SVR .
MS22181	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE The aim of the present prospect i ve clinical study was to compare patient-reported outcomes for maxillary conventional dentures and maxillary implant-supported dentures . MATERIAL AND METHODS Twenty-one patients ( 6 women and 15 men ) being edentulous in the maxilla and encountering problems with their existing dentures were included . Twelve patients ( 4 women and 8 men ) received a new set of conventional dentures , due to insufficient dentures . In nine patients ( 2 women and 7 men ) , the existing dentures were adjusted by means of relining or rebasing . All patients received implant-supported dentures on two retentive anchors . In total , 42 implants were inserted in the anterior maxilla . The participants rated their satisfaction on their existing conventional dentures , 2 months after insertion of new conventional dentures and 2 months after insertion of implant-supported dentures . Thereby , patients responded to question naires capturing the oral health impact profile ( OHIP ) using visual analog scales . Seven domains ( functional limitation , physical pain , psychological discomfort , physical , psychological and social disability and h and icap ) were assessed . Higher scores implied poorer patient satisfaction . In addition , the question naire involved the evaluation of cleaning ability , general satisfaction , speech , comfort , esthetics , stability , and chewing ability . Higher scores implied higher patient satisfaction . RESULTS Patient satisfaction significantly increased for implant-supported dentures compared with old dentures in all seven OHIP subgroups , as well as for cleaning ability , general satisfaction , ability to speak , comfort , esthetics , and stability ( P < 0.05 ) . The comparison of new conventional dentures and implant-supported dentures revealed a statistically significantly increased satisfaction for functional limitation ( difference of 33.2 mm ) , psychological discomfort ( difference of 36.7 mm ) , physical disability ( difference of 36.3 mm ) , and social disability ( difference of 23.5 mm ) , ( P < 0.05 ) . Additionally , general satisfaction , chewing ability , speech , and stability significantly improved in implant-supported dentures ( P < 0.05 ) . CONCLUSIONS Within the limits of this study , maxillary dentures retained by two implants provided some significant short-term improvements over conventional dentures in oral- and health-related quality of life PURPOSE The aim of the study was to compare the differences in the long-term clinical and radiologic effects for three different treatment strategies with implant-supported overdentures in the edentulous m and ible , with a special emphasis on smoking . MATERIAL S AND METHODS In a r and omized- controlled clinical trial , 110 edentulous patients participated . Thirty-six patients were treated with an overdenture supported by two implants with ball attachments ( 2IBA ) , 37 patients with an overdenture supported by two implants with a bar ( 2ISB ) and 37 patients with an overdenture supported by four implants with a triple bar ( 4ITB ) . After a mean evaluation period of 8.3 years , the clinical and radiographic parameters were evaluated . RESULTS Ninety-four out of the original 110 patients ( = 85 % ) were evaluated . In the 2IBA group , the plaque index was significantly lower ( vs. 2ISB , P=0.013 ; vs. 4ITB , P=0.001 ) than in the other groups , but there was no correlation with the other peri-implant parameters . In the 4ITB group , the marginal bone loss was significantly higher than that in the two implant groups . The maximal probing depth was correlated with peri-implant bone loss ( P=0.011 ) . Smoking almost doubled marginal bone loss irrespective of the treatment strategy chosen . CONCLUSIONS Patients with two implants show less marginal bone loss than those with four implants . Smoking is a risk factor for the survival of dental implants in the long run PURPOSE The present study evaluated implant survival/success rate , peri-implant parameters and prosthodontic maintenance efforts for four implant-supported m and ibular overdentures ( IOD ) rigidly retained on either milled bar or double crowns ( telescopic ) attachments . MATERIAL AND METHODS In a r and omized prospect i ve trial , 51 patients with edentulism received four m and ibular interforaminal implants and complete maxillary dentures . For IOD , rigid denture stabilization was chosen r and omly selecting 26 patients for milled bars ( group I ) and 25 patients for double ( telescopic ) crowns ( group II ) . During a 3-year follow-up period , implant survival/success , peri-implant parameters ( marginal bone resorption , pocket depth , plaque- , bleeding- , gingival index [ BI and GI ] , calculus ) and prosthodontic maintenance efforts were evaluated and compared between both retention modalities used . RESULTS Forty-five patients ( 23 group I , 22 group II ) were available for a 3-year follow-up ( dropout rate : 11.8 % ) presenting a high implant survival/success rate ( 100 % ) . Peri-implant marginal bone resorption , pocket depth as well as BI and GI did not differ for both rigid retention modalities . However , annually higher values for plaque- ( NS ) and calculus index ( P<0.035 ) were noticed for the bar ( group I ) than for the telescopic crown ( group II ) attachments . Prevalence of prosthodontic maintenance did not differ between both retention modalities ( group I : 0.41/maintenance efforts/year/ patients vs. group II ; 0.45 maintenance/efforts/year/ patients ) . However , prosthodontic adaption for h and ling mechanism showed benefits for the bar retention . CONCLUSION Rigid anchoring of IOD retained either by bar or telescopic attachments showed high implant success rates and minor prosthodontic maintenance efforts regardless of retention modalities used . Stable denture retention presented healthy peri-implant structure for implants in bar and telescopic anchoring systems . Drawbacks such as higher plaque/calculus for bar retention and less favorable h and ling properties ( output ) for telescopic crown attachment leave the decision on the selection at the discretion of the clinician Treatment of the atrophic edentulous maxilla is challenging especially when bone graft procedures are necessary . In this study an onlay bone graft , a saddle or veneer , with or without maxillary sinus floor inlay graft , harvested from the anterior iliac crest , in combination with implants was used in the reconstruction of patients with extreme atrophy in their maxillae . The aim was to investigate treatment outcome , and the impact of gender and smoking , in 44 patients in a prospect i ve , long-term , follow-up study concerning implant survival rate and marginal bone loss adjacent to the surfaces of the implant . Mean follow-up time was 11 years . Of 334 inserted Brånemark implants , with machined surface , 27 failed . Estimated implant survival rate was 90 % . Marginal bone loss was 1.8 mm 1 year after implant surgery ; 2.3 mm after 5 years ; and 2.4 mm after 10 years . There was a significant difference between genders in implant survival . Marginal bone loss differed significantly between smokers and non-smokers up to the 5-year examination and between genders after the 4-year examination . The onlay bone graft , with or without a maxillary inlay graft , results in high implant survival rate , good oral function and stabilised marginal bone . All patients are still wearing their original fixed bridges BACKGROUND Long-term follow-up studies ( i.e. , over 5 years ) , focusing on prosthetic outcomes and maintenance of implant-supported reconstructions in the edentulous maxilla , are scarce in the literature . PURPOSE The purpose of this study was to evaluate and report 10-year data on outcomes and maintenance of screw-retained implant-supported full-arch casted titanium-resin prostheses in the edentulous maxilla . MATERIAL S AND METHODS In the r and omized control trial cohort of 24 patients , the outcome and maintenance of 23 bridges were registered . RESULTS One patient dropped out of the study prior to the 10-year control . Of the 23 remaining patients , 21 still had their original frameworks ; one framework fractured after 8 years and one was remade after 7 years to create better support for the acrylic . The remaining 23 prostheses showed criteria of success , survival , and failure in 9 , 82 , and 9 % , respectively . Tightening of two assembly screws was necessary in one patient . No detrimental effects were seen because of long cantilever extensions or opposing dentition . A total of 4.7 resin-related complications per prosthesis were observed ; tooth fracture was the most common prosthetic complication . There was an indication of greater prevention in the number of resin-related complications with the use of lingual gold onlay compared with a resilient mouth guard , 0.71 and 1.67 , respectively per bridge . The bridges were removed and reinserted 0.83 times per patient . No abutment or abutment screw fractures were registered . CONCLUSION Fracture or wear of the reconstruction material s were considered predictable risks when using resin-based suprastructure material s. Status of opposing dentition and length of cantilevers did not confer additional risk . The use of a lingual gold onlay indicated prevention of resin-related complications . Future research should focus on the suprastructure material s to predict better overall treatment results of implant-supported full-arch bridges in the edentulous maxilla STATEMENT OF PROBLEM There is a widespread belief that maxillary overdenture prostheses are associated with a higher frequency of complications and require more maintenance than fixed implant prostheses . PURPOSE This prospect i ve clinical study compared the treatment outcomes of fixed and removable implant-supported restorations in the edentulous maxilla with the main emphasis on the clinician 's point of view . MATERIAL AND METHODS Ten patients were treated with fixed screw-retained implant prostheses ( group 1 ) , and 10 patients were treated with removable implant-supported overdentures ( group 2 ) in the edentulous maxilla . Recall was scheduled at 6-month intervals to investigate the prosthodontic treatment outcomes , including implant survival , prosthesis time until retreatment , and maintenance issues . Clinical parameters gingival index ( GI ) , plaque index ( PI ) , the clinical attachment level , and radiographic marginal bone levels measured , along with any biologic and mechanical complications were recorded . RESULTS Patients were followed over a mean period of 39 months ( SD=7 ; group 1 ) and 27 months ( SD=10 ; group 2 ) after implant placement . Cumulative implant survival was 97.6 % for group 1 and 94.4 % for group 2 after an 18-month observation period . The mean time until retreatment after prostheses insertion was 23.4 months for group 1 and 19.8 months for group 2 ( n.s . ) . In both groups , the increase over time in the radiographically investigated bone level was found to be significant . The indices given for the mucosal health and oral hygiene status ( GI and PI ) were highly correlated in both groups at each recall appointment , but no significant differences were found between groups 1 and 2 . CONCLUSION In groups 1 and 2 , comparable prosthodontic treatment outcomes were achieved . The majority of mechanical complications could be managed chairside during recall visits and did not require additional appointments , so that the time and costs involved in providing maintenance were kept down BACKGROUND Dental implants with moderately rough surfaces are commonly used in the treatment of edentulous patients . However , long-term data on survival rates and marginal bone conditions are lacking . PURPOSE This prospect i ve study evaluated the cumulative survival rate of the TiOblast implant ( Astra Tech AB , Mölndal , Sweden ) after 10 years of prosthetic loading . MATERIAL S AND METHODS A total of 199 TiOblast implants were placed in 36 consecutive edentulous patients ( 23 males and 13 females ) . All patients were treated at one clinic and by the same team . The patients were edentulous in either the maxilla ( n = 16 ) or the m and ible ( n = 20 ) . The average age of the patients at the start of the trial was 64 years ( range , 59 - 82 years ) . Of the 199 implants inserted 108 were in the m and ible and 91 were in the maxilla . Clinical evaluations were undertaken after completion of the prosthetic superstructure ( baseline ) and after 6 months , 1 year , 3 years , 5 years , 7 years , and 10 years . Mean marginal bone level was evaluated for the first 100 placed implants for up to 7 years . RESULTS Six implants failed during the study ( 3 in the m and ible and 3 in the maxilla ) . All failures occurred within the first year , giving a cumulative survival rate of 96.9 % ( 96.6 % in the maxilla and 97.2 % in the m and ible ) after 10 years of follow-up . The survival rate for the superstructures was 100 % . The mean marginal bone level in the measured sample was 0.2 mm ( st and ard deviation [ SD ] , 0.31 ) below the reference point at baseline , 0.28 mm ( SD , 0.20 ) and 1.27 mm ( SD , 1.15 ) below the same point 7 years later ( mean , 0.15 mm per year ) . CONCLUSION This study showed that titanium dioxide-blasted implants offer predictable long-term results as supports for fixed prostheses in both the maxilla and m and ible PURPOSE The present study evaluated implant and peri-implant out Output:	Implant location , type of restoration , and implant number do have an influence on the estimated implant loss rate .
MS22182	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background In Malawi , there has been a return of Plasmodium falciparum sensitivity to chloroquine ( CQ ) since sulfadoxine-pyrimethamine ( SP ) replaced CQ as first line treatment for uncomplicated malaria . When used for prophylaxis , Amodiaquine ( AQ ) was associated with agranulocytosis but is considered safe for treatment and is increasingly being used in Africa . Here we compare the efficacy , safety and selection of resistance using SP or CQ+SP or artesunate (ART)+SP or AQ+SP for the treatment of uncomplicated falciparum malaria . Methodology and Findings 455 children aged 1–5 years were recruited into a double-blinded r and omised trial comparing SP to the three combination therapies . Using intention to treat analysis with missing outcomes treated as successes , and without adjustment to distinguish recrudescence from new infections , the day 28 adequate clinical and parasitological response ( ACPR ) rate for SP was 25 % , inferior to each of the three combination therapies ( p<0.001 ) . AQ+SP had an ACPR rate of 97 % , higher than CQ+SP ( 81 % ) and ART+SP ( 70 % ) , p<0.001 . Nineteen children developed a neutropenia of ≤0.5 × 103 cells/µl by day 14 , more commonly after AQ+SP ( p = 0.03 ) . The mutation pfcrt 76 T , associated with CQ resistance , was detected in none of the pre-treatment or post-treatment parasites . The prevalence of the pfmdr1 86Y mutation was higher after treatment with AQ+SP than after SP , p = 0.002 . Conclusions The combination AQ+SP was highly efficacious , despite the low efficacy of SP alone ; however , we found evidence that AQ may exert selective pressure for resistance associated mutations many weeks after treatment . This study confirms the return of CQ sensitivity in Malawi and importantly , shows no evidence of the re-emergence of pfcrt 76 T after treatment with CQ or AQ . Given the safety record of AQ when used as a prophylaxis , our observations of marked falls in neutrophil counts in the AQ+SP group requires further scrutiny . Trial Registration Controlled-Trials.com IS RCT Background Sulphadoxine-pyrimethamine ( SP ) a widely used treatment for uncomplicated malaria and recommended for intermittent preventive treatment of malaria in pregnancy , is being investigated for intermittent preventive treatment of malaria in infants ( IPTi ) . High levels of drug resistance to SP have been reported from north-eastern Tanzania associated with mutations in parasite genes . This study compared the in vivo efficacy of SP in symptomatic 6–59 month children with uncomplicated malaria and in asymptomatic 2–10 month old infants . Methodology and Principal Findings An open label single arm ( SP ) st and ard 28 day in vivo WHO antimalarial efficacy protocol was used in 6 to 59 months old symptomatic children and a modified protocol used in 2 to 10 months old asymptomatic infants . Enrolment was stopped early ( 87 in the symptomatic and 25 in the asymptomatic studies ) due to the high failure rate . Molecular markers were examined for recrudescence , re-infection and markers of drug resistance and a review of literature of studies looking for the 581 G dhps mutation was carried out . In symptomatic children PCR-corrected early treatment failure was 38.8 % ( 95 % CI 26.8–50.8 ) and total failures by day 28 were 82.2 % ( 95 % CI 72.5–92.0 ) . There was no significant difference in treatment failures between asymptomatic and symptomatic children . 96 % of sample s carried parasites with mutations at codons 51 , 59 and 108 in the dhfr gene and 63 % carried a double mutation at codons 437 and 540 . 55 % carried a third mutation with the addition of a mutation at codon 581 in the dhps gene . This triple : triple haplotype maybe associated with earlier treatment failure . Conclusion In northern Tanzania SP is a failed drug for treatment and its utility for prophylaxis is doubtful . The study found a new combination of parasite mutations that maybe associated with increased and earlier failure . Trial Registration Clinical Trials.gov Intermittent preventive treatment in pregnancy ( IPTp ) is used to prevent Plasmodium falciparum malaria . However , parasites resistant to the IPTp drug sulfadoxine-pyrimethamine ( SP ) have emerged worldwide , and infections with mixed resistant and susceptible parasites are exacerbated by pyrimethamine in mice . In a prospect i ve delivery cohort in Muheza , Tanzania , we examined the effects of SP IPTp on parasite resistance alleles , parasite diversity , level of parasitemia , and inflammation in the placenta . IPTp use was associated with an increased fraction of parasites carrying the resistance allele at DHPS codon 581 , an increase in the level of parasitemia , and more intense placental inflammation . The lowest mean level of parasite diversity and highest mean level of parasitemia occurred in women after recent IPTp use . These findings support a model of parasite release and facilitation , whereby the most highly resistant parasites out-compete less fit parasite population s and overgrow under drug pressure . Use of partially effective anti-malarial agents for IPTp may exacerbate malaria infections in the setting of widespread drug resistance OBJECTIVE To assess the efficacy at individual level of intermittent preventive treatment with sulfadoxine-pyrimethamine ( IPTp-SP ) in primi- and secundigravidae in rural Burkina Faso . METHODS Data of 1441 women enrolled in a health centre r and omized trial and delivering a live-singleton between September 2004 and October 2006 were analysed at individual level . Prevalence of peripheral and placental parasitaemia , anaemia ( PCV < 33 % ) , low-birth weight ( < 2500 g ; LBW ) , mean packed cell volume ( PCV ) and birth weight were compared in relation to the number of directly observed SP doses . RESULTS Two or more doses of SP significantly reduced the risk of placental parasitaemia [ adjusted odds ratio ( AOR ) = 0.04 , 95%CI = 0.003 - 0.60 , P = 0.023 ] and anaemia at delivery ( AOR = 0.31 , 95%CI = 0.18 - 0.52 , P < 0.001 ) . IPTp was associated with reduced risk of LBW in primigravidae ( AOR = 0.11 , 95%CI = 0.07 - 0.17 , P < 0.001 ) but not secundigravidae ( AOR = 0.70 , 95%CI = 0.26 - 1.91 , P = 0.452 ) . For each increment in number of SP doses mean PCV increased by 1.0 % ( 95%CI = 0.4 - 1.7 , P = 0.005 ) at 32 weeks gestation , by 1.2 % ( 95%CI = 0.2 - 2.2 , P = 0.025 ) at delivery and mean birth weight by 220 g ( 95%CI = 134 - 306 P < 0.001 ) in primigravidae and by 102 g ( 95%CI = 55 - 148 , P = 0.001 ) in secundigravidae . CONCLUSION The risk of malaria infection was significantly reduced by IPTp with SP in primi- and secundigravidae in rural Burkina Faso . The impact on clinical outcomes is lower and mainly limited to primigravidae for LBW . Incomplete uptake of IPTp-SP and limited effect in low risk groups together may substantially dilute the measurable impact of effective interventions . This needs to be taken into account when evaluating interventions at community level Abstract .The safety and efficacy of a fixed 25 mg pyrimethamine-500 mg sulfadoxine combination supplemented with 15 mg folinic acid twice a week as primary prophylaxis of Pneumocystis carinii pneumonia ( PCP ) and toxoplasmic encephalitis was evaluated in 106 patients infected with the human immunodeficiency virus . All patients had a CD4 + T-lymphocyte count of less than 100 cells/μl at study entry . Efficacy in this single-arm open-label prospect i ve study was analyzed on an as-treated basis . No patient received highly active antiretroviral treatment , including protease inhibitors or non-nucleoside reverse transcriptase inhibitors , while on study medication . PCP developed in four patients , one of whom had been noncompliant . No PCP episode occurred in the first year . Probabilities of freedom from PCP were 0.97 ( 95%CI , 0.92–1 ) after 24 months and 0.93 ( 95%CI , 0.84–1 ) after 36 months . Of 74 ( 69.8 % ) patients positive for anti-toxoplasma IgG antibodies , one noncompliant patient developed toxoplasmic encephalitis after 24 months . Allergic reactions were observed in 18 ( 17 % ) patients and result ed in permanent discontinuation in 7 ( 6.6 % ) patients . One ( 0.9 % ) patient who had continued prophylaxis despite progressive hypersensitivity reactions developed a serious adverse reaction ( Stevens-Johnson syndrome ) . The median survival of study participants was 29 months , with relentless progression of AIDS accounting for most deaths . The prophylaxis regimen studied appeared safe and effective for primary prophylaxis of PCP and toxoplasmic encephalitis . Severe adverse events can likely be prevented by discontinuation of prophylaxis at the time allergic reactions are noted . Rechallenge frequently results in tolerance . Efficacy and safety compare favorably with previously studied regimens . This simple prophylactic regimen may provide a convenient alternative for patients failing or intolerant to approved regimens This study examines the relationship between malaria treatment failure after sulfadoxine-pyrimethamine ( S-P ) chemotherapy and presence of mutations in the Plasmodium falciparum dihydropteroate synthase ( dhps ) and dihydrofolate reductase ( dhfr ) genes ( associated with resistance in vitro to S and P ) before treatment . In Kenya , 38 malaria patients in a holoendemic area , and 21 in an epidemic area , participated in the trial in 1997 - 98 . In the 2 areas , drug failure occurred in 76 % and 75 % of cases where any mutation in dhfr was seen ( positive predictive values 76 % and 75 % : P = 0.003 and 0.008 ) and an identical association was seen with dhfr Asn-108 . In the holoendemic area all occurrences of > or = 2 mutations in dhfr predicted drug failure . Only 3 instances were seen in the epidemic focus , but treatment failed in all . Only in the epidemic focus , 7 ( 88 % ) of 8 occurrences of > or = 1 mutations in dhps , and all occurrences of the Gly-437 allele of dhps , predicted failure . Association between mutations in dhps and mutations in dhfr was noted in the combined sites , irrespective of outcome . Although this makes the relationship of combined dhfr and dhps mutations to failure more difficult to interpret , it nevertheless supports S-P selection acting on both genes . In the holoendemic site , treatment success increased with age . In this location , acquired immunity may mask the impact of mutations in dhps , since sulfadoxine is a less effective treatment than pyrimethamine ABSTRACT Antifolate drugs have an important role in the treatment of malaria . Polymorphisms in the genes encoding the dihydrofolate reductase and dihydropteroate synthetase enzymes cause resistance to the antifol and sulfa drugs , respectively . Rw and a has the highest levels of antimalarial drug resistance in Africa . We correlated the efficacy of chlorproguanil-dapsone plus artesunate ( CPG-DDS+A ) and amodiaquine plus sulfadoxine-pyrimethamine ( AQ+SP ) in children with uncomplicated malaria caused by Plasmodium falciparum parasites with pfdhfr and pfdhps mutations , which are known to confer reduced drug susceptibility , in two areas of Rw and a. In the eastern province , where the cure rates were low , over 75 % of isolates had three or more pfdhfr mutations and two or three pfdhps mutations and 11 % had the pfdhfr 164-Leu polymorphism . In the western province , where the cure rates were significantly higher ( P < 0.001 ) , the prevalence of multiple resistance mutations was lower and the pfdhfr I164L polymorphism was not found . The risk of treatment failure following the administration of AQ+SP more than doubled for each additional pfdhfr resistance mutation ( odds ratio [ OR ] = 2.4 ; 95 % confidence interval [ CI ] = 1.01 to 5.55 ; P = 0.048 ) and each pfdhps mutation ( OR = 2.1 ; 95 % CI = 1.21 to Output:	There appears to be a prevalence of 581 G above which IPTp-SP no longer protects against LBW .
MS22183	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objectives . Antimicrobial treatment may disturb the colonization resistance of gastrointestinal microflora , which may induce clinical symptoms , most commonly diarrhea . The severity of antibiotic-associated diarrhea may range from a brief , self-limiting disease to devastating diarrhea with electrolyte disturbances , dehydration , crampy abdominal pain , pseudomembranous colitis , toxic megacolon , or even death . The incidence of diarrhea in children receiving a single antimicrobial treatment is unclear . In addition to more critical use of antimicrobials , adjunctive preventive measures to antibiotic-associated diarrhea are needed . The objective of this study was to evaluate the incidence of diarrhea after antimicrobial treatment in children with no history of antimicrobial use during the previous 3 months . Another aim of this study was to assess the preventive potential of Lactobacillus rhamnosus GG ( Lactobacillus GG ; American Type Culture Collection 53103 ) , a probiotic strain with a documented safety record and a therapeutic effect in viral gastroenteritis on antibiotic-associated diarrhea . Methods . Oral antimicrobial agents were prescribed for the treatment of acute respiratory infections at the clinics of the Health Care Center of the City of Tampere or Tampere University Hospital , Finl and , to 167 patients who were invited to participate in the study . Of the patients , 48 were lost to follow-up ; therefore , the final study population consisted of 119 children from 2 weeks to 12.8 years of age ( mean : 4.5 years ) . All study subjects met the inclusion criteria : they had not received any antimicrobial medication during the previous 3 months , they did not suffer from gastrointestinal disorders , and they did not need intravenous antimicrobial treatment . The patients were r and omized to receive placebo or 2 × 1010 colony-forming units of Lactobacillus GG in capsules given twice daily during the antimicrobial treatment . Lactobacillus GG and placebo capsules were indistinguishable in appearance and taste . The parents kept a daily symptom diary and recorded stool frequency and consistency at home for 3 months . Diarrhea was defined as at least three watery or loose stools per day for a minimum of 2 consecutive days . In the case of diarrhea , viral ( adenovirus , rotavirus , calicivirus and astrovirus ) and bacterial ( Salmonella , Shigella , Yersinia , Campylobacter , Clostridium difficile , Staphylococcus aureus , and yeasts ) analyses were studied in fecal sample s. The metabolic activity of the gut microflora was assessed by analysis of fecal urease , β-glucosidase , and β-glucuronidase activities . The primary outcome measure was diarrhea during the first 2 weeks after the beginning of the antimicrobial treatment , because this period most likely reflects the effects of antimicrobial use . Secondary outcome measures were the activities of fecal urease , β-glucuronidase , and β-glucosidase . Results . On the entire follow-up , 80 % of any gastrointestinal symptoms were reported during the first 2 weeks after the beginning of the antimicrobial treatment . The incidence of diarrhea was 5 % in the Lactobacillus GG group and 16 % in the placebo group within 2 weeks of antimicrobial therapy ( χ2 = 3.82 ) . The treatment effect ( 95 % confidence interval ) of Lactobacillus GG was −11 % ( −21%–0 % ) . In diarrheal episodes , the viral and bacterial analyses were positive for Clostridium difficile in 2 cases and for Norwalk-like calicivirus in 3 cases . The age of the patients with diarrhea was between 3 months and 5 years in 75 % of cases in both groups . The severity of diarrhea was comparable in the study groups , as evidence d by similar stool frequency ( mean : 5 per day ; range : 3–6 ) and the duration of diarrhea ( mean : 4 days ; range : 2–8 ) . The activities of fecal urease and β-glucuronidase , but not β-glucosidase , changed significantly after the beginning of the antimicrobial treatment in the Lactobacillus GG group and in the placebo group alike . The decrease in urease and β-glucuronidase activities was reversible in patients with no diarrhea , but in patients with diarrhea , the modifications in gut microflora were more profound and prolonged . The activities of the three enzymes were normalized within 3 weeks , evidence d by stable enzyme activities in sample s collected 3 weeks , 1 month , and 3 months after the beginning of the antimicrobial treatment , compared with those obtained before treatment . Discussion . In the present study , after a single antimicrobial treatment , the incidence of diarrhea was 16 % . The higher incidence of antibiotic-associated diarrhea in previous reports may be attributable to a recent antimicrobial therapy that disturbs intestinal flora and exposes to complications . Also , in the present study , changes in the metabolic activity of the intestinal flora were observed , evidence d by a transient decline in fecal enzyme activities . Different probiotic preparations , including lactobacilli , are recommended frequently to prevent antibiotic-associated diarrhea . Although probiotics have been shown to be efficient in the prevention and the treatment of viral gastroenteritis , their usefulness during antimicrobial therapy in children has not been eluci date d before . We observed that the administration of Lactobacillus GG to children receiving antimicrobial therapy for respiratory infection reduced the incidence of antibiotic-associated diarrhea to one third . The beneficial effect may be mediated by a number of functions of probiotics , ie , production of antimicrobial substances , local competition of adhesion receptors and nutrients , and stimulation of intestinal antigen specific and nonspecific immune responses . Conclusion . A probiotic strain , Lactobacillus GG , is effective in the prevention of diarrhea in children receiving antimicrobial treatment to respiratory infections Background & Aims Intestinal inflammation is a hallmark of cystic fibrosis ( CF ) . Administration of probiotics can reduce intestinal inflammation and the incidence of pulmonary exacerbations . We investigated the composition of intestinal microbiota in children with CF and analyzed its relationship with intestinal inflammation . We also investigated the microflora structure before and after Lactobacillus GG ( LGG ) administration in children with CF with and without antibiotic treatment . Methods The intestinal microbiota were analyzed by denaturing gradient gel electrophoresis ( DGGE ) , real-time polymerase chain reaction ( RT-PCR ) , and fluorescence in situ hybridization ( FISH ) . Intestinal inflammation was assessed by measuring fecal calprotectin ( CLP ) and rectal nitric oxide ( rNO ) production in children with CF as compared with healthy controls . We then carried out a small double-blind r and omized clinical trial with LGG . Results Twenty-two children with CF children were enrolled in the study ( median age , 7 years ; range , 2–9 years ) . Fecal CLP and rNO levels were higher in children with CF than in healthy controls ( 184±146 µg/g vs. 52±46 µg/g ; 18±15 vs. 2.6±1.2 µmol/L NO2 − , respectively ; P<0.01 ) . Compared with healthy controls , children with CF had significantly different intestinal microbial core structures . The levels of Eubacterium rectale , Bacteroides uniformis , Bacteroides vulgatus , Bifidobacterium adolescentis , Bifidobacterium catenulatum , and Faecalibacterium prausnitzii were reduced in children with CF . A similar but more extreme pattern was observed in children with CF who were taking antibiotics . LGG administration reduced fecal CLP and partially restored intestinal microbiota . There was a significant correlation between reduced microbial richness and intestinal inflammation . Conclusions CF causes qualitative and quantitative changes in intestinal microbiota , which may represent a novel therapeutic target in the treatment of CF . Administration of probiotics restored gut microbiota , supporting the efficacy of probiotics in reducing intestinal inflammation and pulmonary exacerbations . Trial Registration Clinical Trials.gov NCT Objective To compare the efficacy of five probiotic preparations recommended to parents in the treatment of acute diarrhoea in children . Design R and omised controlled clinical trial in collaboration with family paediatricians over 12 months . Setting Primary care . Participants Children aged 3 - 36 months visiting a family paediatrician for acute diarrhoea . Intervention Children 's parents were r and omly assigned to receive written instructions to purchase a specific probiotic product : oral rehydration solution ( control group ) ; Lactobacillus rhamnosus strain GG ; Saccharomyces boulardii ; Bacillus clausii ; mix of L delbrueckii var bulgaricus , Streptococcus thermophilus , L acidophilus , and Bifidobacterium bifidum ; or Enterococcus faecium SF68 . Main outcome measures Primary outcomes were duration of diarrhoea and daily number and consistency of stools . Secondary outcomes were duration of vomiting and fever and rate of admission to hospital . Safety and tolerance were also recorded . Results 571 children were allocated to intervention . Median duration of diarrhoea was significantly shorter ( P<0.001 ) in children who received L rhamnosus strain GG ( 78.5 hours ) and the mix of four bacterial strains ( 70.0 hours ) than in children who received oral rehydration solution alone ( 115.0 hours ) . One day after the first probiotic administration , the daily number of stools was significantly lower ( P<0.001 ) in children who received L rhamnosus strain GG and in those who received the probiotic mix than in the other groups . The remaining preparations did not affect primary outcomes . Secondary outcomes were similar in all groups . Conclusions Not all commercially available probiotic preparations are effective in children with acute diarrhoea . Paediatricians should choose bacterial preparations based on effectiveness data . Trial registration number Current Controlled Trials IS RCT N56067537 Objective To estimate the efficacy of a probiotic yogurt compared to a pasteurised yogurt for the prevention of antibiotic-associated diarrhoea in children . Design and setting This was a multisite , r and omised , double-blind , placebo-controlled clinical trial conducted between September 2009 and 2012 . The study was conducted through general practice s and pharmacies in Launceston , Tasmania , Australia . Participants and interventions Children ( aged 1–12 years ) prescribed antibiotics , were r and omised to receive 200 g/day of either yogurt ( probiotic ) containing Lactobacillus rhamnosus GG ( LGG ) , Bifidobacterium lactis ( Bb-12 ) and Lactobacillus acidophilus ( La-5 ) or a pasteurised yogurt ( placebo ) for the same duration as their antibiotic treatment . Outcomes Stool frequency and consistency were recorded for the duration of treatment plus 1 week . Primary outcome was stool frequency and consistency , classified at different levels of diarrhoea severity . Due to the small number of cases of diarrhoea , comparisons between groups were made using Fisher 's exact analysis . Results 72 children commenced and 70 children ( 36 placebo and 34 probiotic ) completed the trial . There were no incidents of severe diarrhoea ( stool consistency ≥6 , ≥3 stools/day for ≥2 consecutive days ) in the probiotic group and six in the placebo group ( Fisher 's exact p=0.025 ) . There was also only one episode of minor diarrhoea ( stool consistency ≥5 , ≥2 stools/day for ≥2 days in the probiotic group compared to 21 in the placebo group ( Fisher 's exact p<0.001 ) . The probiotic group reported fewer adverse events ( 1 had abdominal pain , 1 vomited and 1 had headache ) than the placebo group ( 6 had abdominal pain , 4 had loss of appetite and 1 had nausea ) . Conclusions A yogurt combination of LGG , La-5 and Bb-12 is an effective method for reducing the incidence of antibiotic-associated diarrhoea in children . Trial registration number Australian New Zeal and Clinical Trials Registry Balanced glucose metabolism ensures optimal fetal growth with long-term health implication s conferred on both mother and child . We examined whether supplementation of probiotics with dietary counselling affects glucose metabolism in normoglycaemic pregnant women . At the first trimester of pregnancy 256 women were r and omised to receive nutrition counselling to modify dietary intake according to current recommendations or as controls ; the dietary intervention group was further r and omised to receive probiotics ( Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12 ; diet/probiotics ) or placebo ( diet/placebo ) in a double-blind manner , whilst the control group received placebo ( control/placebo ) . Blood glucose concentrations were lowest in Output:	The present review did not find convincing evidence that these assumptions are valid . There is , however , also no strong evidence that the assumptions are incorrect and /or that there is antagonistic activity between strains in a combination .
MS22184	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Patients with type 2 diabetes mellitus ( T2DM ) with a glycated haemoglobin ( HbA1c ) level ≥7 and ≤10 % were r and omized to receive empagliflozin 12.5 mg twice daily ( n = 219 ) , 25 mg once daily ( n = 218 ) , 5 mg twice daily ( n = 219 ) or 10 mg once daily ( n = 220 ) , or placebo ( n = 107 ) as add‐on to stable‐dose metformin immediate release ( IR ) twice daily for 16 weeks . The primary endpoint was change from baseline in HbA1c at week 16 . At week 16 , change from baseline in HbA1c with empagliflozin twice daily was non‐inferior to empagliflozin once daily and vice versa . The adjusted mean ( 95 % confidence interval ) difference in change from baseline in HbA1c with empagliflozin 12.5 mg twice daily versus 25 mg once daily was −0.11 % ( −0.26 , 0.03 ) , and with empagliflozin 5 mg twice daily versus 10 mg once daily it was −0.02 % ( −0.16 , 0.13 ) . All empagliflozin regimens were well tolerated ; thus , when used as add‐on to metformin IR in patients with T2DM , the therapeutic effect of empagliflozin twice‐daily and once‐daily regimens can be considered equivalent OBJECTIVE To evaluate the efficacy and safety of combinations of empagliflozin/linagliptin as second-line therapy in subjects with type 2 diabetes inadequately controlled on metformin . RESEARCH DESIGN AND METHODS Subjects were r and omized to a combination of empagliflozin 25 mg/linagliptin 5 mg ( n = 137 ) , empagliflozin 10 mg/linagliptin 5 mg ( n = 136 ) , empagliflozin 25 mg ( n = 141 ) , empagliflozin 10 mg ( n = 140 ) , or linagliptin 5 mg ( n = 132 ) as add-on to metformin for 52 weeks . The primary end point was change from baseline in HbA1c at week 24 . RESULTS At week 24 , reductions in HbA1c ( mean baseline 7.90–8.02 % [ 62.8–64.1 mmol/mol ] ) with empagliflozin/linagliptin were superior to those with empagliflozin or linagliptin alone as add-on to metformin ; adjusted mean ( SE ) changes from baseline were −1.19 % ( 0.06 ) ( −13.1 mmol/mol [ 0.7 ] ) with empagliflozin 25 mg/linagliptin 5 mg , −1.08 % ( 0.06 ) ( −11.8 mmol/mol [ 0.7 ] ) with empagliflozin 10 mg/linagliptin 5 mg , −0.62 % ( 0.06 ) ( −6.8 mmol/mol [ 0.7 ] ) with empagliflozin 25 mg , −0.66 % ( 0.06 ) ( −7.2 mmol/mol [ 0.7 ] ) with empagliflozin 10 mg , and −0.70 % ( 0.06 ) ( −7.6 mmol/mol [ 0.7 ] ) with linagliptin 5 mg ( P < 0.001 for all comparisons ) . In these groups , respectively , 61.8 , 57.8 , 32.6 , 28.0 , and 36.1 % of subjects with baseline HbA1c ≥7 % ( ≥53 mmol/mol ) had HbA1c < 7 % ( < 53 mmol/mol ) at week 24 . Efficacy was maintained at week 52 . The proportion of subjects with adverse events ( AEs ) over 52 weeks was similar across treatment arms ( 68.6–73.0 % ) , with no hypoglycemic AEs requiring assistance . CONCLUSIONS Combinations of empagliflozin/linagliptin as second-line therapy for 52 weeks significantly reduced HbA1c compared with the individual components and were well tolerated Background Despite the number of medications for type 2 diabetes , many people with the condition do not achieve good glycaemic control . Some existing glucose-lowering agents have adverse effects such as weight gain or hypoglycaemia . Type 2 diabetes tends to be a progressive disease , and most patients require treatment with combinations of glucose-lowering agents . The sodium glucose co-transporter 2 ( SGLT2 ) receptor inhibitors are a new class of glucose-lowering agents . Objective To assess the clinical effectiveness and safety of the SGLT2 receptor inhibitors in dual or triple therapy in type 2 diabetes . Data sources MEDLINE , Embase , Cochrane Library ( all sections ) ; Science Citation Index ; trial registries ; conference abstract s ; drug regulatory authorities ; bibliographies of retrieved papers . Inclusion criteria R and omised controlled trials of SGLT2 receptor inhibitors compared with placebo or active comparator in type 2 diabetes in dual or combination therapy . Methods Systematic review . Quality assessment used the Cochrane risk of bias score . Results Seven trials , published in full , assessed dapagliflozin and one assessed canagliflozin . Trial quality appeared good . Dapagliflozin 10 mg reduced HbA1c by −0.54 % ( weighted mean differences ( WMD ) , 95 % CI −0.67 to −0.40 ) compared to placebo , but there was no difference compared to glipizide . Canagliflozin reduced HbA1c slightly more than sitagliptin ( up to −0.21 % vs sitagliptin ) . Both dapagliflozin and canagliflozin led to weight loss ( dapagliflozin WMD −1.81 kg ( 95 % CI −2.04 to −1.57 ) , canagliflozin up to −2.3 kg compared to placebo ) . Limitations Long-term trial extensions suggested that effects were maintained over time . Data on canagliflozin are currently available from only one paper . Costs of the drugs are not known so cost-effectiveness can not be assessed . More data on safety are needed , with the Food and Drug Administration having concerns about breast and bladder cancers . Conclusions Dapagliflozin appears effective in reducing HbA1c and weight in type 2 diabetes , although more safety data are needed Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more OBJECTIVE To investigate the long-term safety and efficacy of empagliflozin , a sodium glucose cotransporter 2 inhibitor ; sitagliptin ; and metformin in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS In this r and omized , open-label , 78-week extension study of two 12-week , blinded , dose-finding studies of empagliflozin ( monotherapy and add-on to metformin ) with open-label comparators , 272 patients received 10 mg empagliflozin ( 166 as add-on to metformin ) , 275 received 25 mg empagliflozin ( 166 as add-on to metformin ) , 56 patients received metformin , and 56 patients received sitagliptin as add-on to metformin . RESULTS Changes from baseline in HbA1c at week 90 were −0.34 to −0.63 % ( −3.7 to −6.9 mmol/mol ) with empagliflozin , −0.56 % ( −6.1 mmol/mol ) with metformin , and −0.40 % ( −4.4 mmol/mol ) with sitagliptin . Changes from baseline in weight at week 90 were −2.2 to −4.0 kg with empagliflozin , −1.3 kg with metformin , and −0.4 kg with sitagliptin . Adverse events ( AEs ) were reported in 63.2–74.1 % of patients on empagliflozin and 69.6 % on metformin or sitagliptin ; most AEs were mild or moderate in intensity . Hypoglycemic events were rare in all treatment groups , and none required assistance . AEs consistent with genital infections were reported in 3.0–5.5 % of patients on empagliflozin , 1.8 % on metformin , and none on sitagliptin . AEs consistent with urinary tract infections were reported in 3.8–12.7 % of patients on empagliflozin , 3.6 % on metformin , and 12.5 % on sitagliptin . CONCLUSIONS Long-term empagliflozin treatment provided sustained glycemic and weight control and was well tolerated with a low risk of hypoglycemia in patients with type 2 diabetes Chronic hyperglycemia impairs insulin action , result ing in glucotoxicity , which can be ameliorated in animal models by inducing glucosuria with renal glucose transport inhibitors . Here , we examined whether reduction of plasma glucose with a sodium-glucose cotransporter 2 ( SGLT2 ) inhibitor could improve insulin-mediated tissue glucose disposal in patients with type 2 diabetes . Eighteen diabetic men were r and omized to receive either dapagliflozin ( n = 12 ) or placebo ( n = 6 ) for 2 weeks . We measured insulin-mediated whole body glucose uptake and endogenous glucose production ( EGP ) at baseline and 2 weeks after treatment using the euglycemic hyperinsulinemic clamp technique . Dapagliflozin treatment induced glucosuria and markedly lowered fasting plasma glucose . Insulin-mediated tissue glucose disposal increased by approximately 18 % after 2 weeks of dapagliflozin treatment , while placebo-treated subjects had no change in insulin sensitivity . Surprisingly , following dapagliflozin treatment , EGP increased substantially and was accompanied by an increase in fasting plasma glucagon concentration . Together , our data indicate that reduction of plasma glucose with an agent that works specifically on the kidney to induce glucosuria improves muscle insulin sensitivity . However , glucosuria induction following SGLT2 inhibition is associated with a paradoxical increase in EGP . These results provide support for the glucotoxicity hypothesis , which suggests that chronic hyperglycemia impairs insulin action in individuals with type 2 diabetes AIMS To evaluate the effects of the sodium glucose cotransporter 2 ( SGLT2 ) inhibitor empagliflozin added to metformin for 12 weeks in patients with type 2 diabetes . METHODS This dose-ranging , double-blind , placebo-controlled trial r and omized 495 participants with type 2 diabetes inadequately controlled on metformin [ haemoglobin A1c ( HbA1c ) > 7 to ≤10 % ] to receive 1 , 5 , 10 , 25 , or 50 mg empagliflozin once daily ( QD ) , or placebo , or open-label sitagliptin ( 100 mg QD ) , added to metformin for 12 weeks . The primary endpoint was change in HbA1c from baseline to week 12 ( empagliflozin groups versus placebo ) . RESULTS Reductions in HbA1c of -0.09 to -0.56 % were observed with empagliflozin after 12 weeks , versus an increase of 0.15 % with placebo ( baseline : 7.8 - 8.1 % ) . Compared with placebo , empagliflozin doses from 5 to 50 mg result ed in reductions in fasting plasma glucose ( -2 to -28 mg/dl vs. 5 mg/dl with placebo ; p < 0.0001 ) and body weight ( -2.3 to -2.9 kg vs. -1.2 kg ; p < 0.01 ) . Frequency of adverse events was generally similar with empagliflozin ( 29.6 - 48.6 % ) , placebo ( 36.6 % ) and sitagliptin ( 35.2 % ) . Hypoglycaemia rates were very low and balanced among groups . Most frequent adverse events with empagliflozin were urinary tract infections ( 4.0 % vs. 2.8 % with placebo ) and pollakiuria ( 2.5 % vs. 1.4 % with placebo ) . Genital infections were reported only with empagliflozin ( 4.0 % ) . CONCLUSIONS Once daily empagliflozin as add-on therapy to metformin was well tolerated except for increased genital infections and result ed in reductions in HbA1c , fasting plasma glucose and body weight in patients with type 2 diabetes inadequately controlled on metformin monotherapy To investigate the long‐term efficacy and safety of Output:	In addition , EMPA as add-on to MET also had a favourable effect on body weight and blood pressure . Conclusions EMPA as add-on to MET was well tolerated and provided additional benefits beyond glucose lowering , such as weight loss and blood pressure reduction .
MS22185	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Hibiscus sabdariffa L. ( Malvaceae ) has been used in different countries as an antihypertensive . Pharmacological work has demonstrated that this effect is probably produced by a diuretic activity and inhibition of the angiotensin-converting enzyme ( ACE ) . Two clinical trials have confirmed the antihypertensive effect using watery infusions , in which a natriuretic effect was also detected . To compare therapeutic effectiveness , tolerability , and safety , as well as the effect on serum electrolytes and the ACE inhibitory effect of a herbal medicinal product prepared from the dried extract of H. sabdariffa calyxes ( HsHMP ) with those of lisinopril on patients with hypertension ( HT ) , a r and omized , controlled , and double-blind clinical trial was conducted . Patients of either sex , 25 - 61 years of age , with hypertension stage I or II , were daily treated for 4 weeks with the HsHMP , 250 mg of total anthocyanins per dose ( experimental group ) , or 10 mg of lisinopril ( control group ) . Outcome variables included effectiveness ( diastolic blood pressure [ DBP ] reduction , > or= 10 mmHg ) , safety ( absence of pathological modifications in the biochemical tests of hepatic and renal function ) , tolerability ( absence of intense side effects ) , effect on serum electrolytes , and effect on ACE activity . Basal analysis included 193 subjects ( 100 in the experimental group ) , while outcome variable analysis integrated 171 . Results showed that the experimental treatment decreased blood pressure ( BP ) from 146.48/97.77 to 129.89/85.96 mmHg , reaching an absolute reduction of 17.14/11.97 mmHg ( 11.58/12.21 % , p < 0.05 ) . The experimental treatment showed therapeutic effectiveness of 65.12 % as well as tolerability and safety of 100 % . BP reductions and therapeutic effectiveness were lower than those obtained with lisinopril ( p < 0.05 ) . Under the experimental treatment , the serum chlorine level increased from 91.71 to 95.13 mmol/L ( p = 0.0001 ) , the sodium level showed a tendency to decrease ( from 139.09 to 137.35 , p = 0.07 ) , while potassium level was not modified . ACE plasmatic activity was inhibited by HsHMP from 44.049 to 30.1 Units ( Us ; p = 0.0001 ) . In conclusion , the HsHMP exerted important antihypertensive effectiveness with a wide margin of tolerability and safety , while it also significantly reduced plasma ACE activity and demonstrated a tendency to reduce serum sodium ( Na ) concentrations without modifying potassium ( K ) levels . Further studies are necessary for evaluating the dose-dependency of HsHMP and for detecting lower effective doses ABSTRACT Introduction : The use of herbal medicines including different types of tea is among the different strategies for preventing and controlling the side-effects of diabetes . The aim of the present study was to compare the effect of sour tea and green tea on mildly hypertensive patients with diabetes . Methods : The present study was a r and omized clinical trial in which 100 mildly hypertensive patients with diabetes were r and omly assigned into sour tea group ( ST ) and green tea group ( GT ) . They were instructed to drink sour tea and green tea infusion , respectively , three times a day 2 hr after each meal for 4 weeks . The participants ’ blood pressure was measured at days 1 , 15 , and at the end of study . Results : The systolic pressure of both groups statistically decreased at the end of the study ; it decreased from 123.1 ± 15.5 to 116.8 ± 16.3 mmHg in the ST and from 119.4 ± 15.1 to 114.8 ± 15.9 mmHg in the GT . The diastolic pressure of both groups statistically decreased by the end of the study ; it decreased from 79.4 ± 11.1 to 74.5 ± 9.3 mmHg in the ST and from 78.9 ± 8.3 to 75.3 ± 7.7 mmHg in the GT . The therapeutic effectiveness of tea drinking by the end of intervention was 43.5 % in the ST and 39.6 % in the GT compared to the beginning . Conclusions : The present study revealed that mildly hypertensive type 2 diabetic individuals who drink three glasses of green or sour tea daily for 4 weeks show significant decreased systolic and diastolic blood pressures Epidemiological studies report that quercetin , an antioxidant flavonol found in apples , berries , and onions , is associated with reduced risk of coronary heart disease and stroke . Quercetin supplementation also reduces blood pressure in hypertensive rodents . The efficacy of quercetin supplementation to lower blood pressure in hypertensive humans has never been evaluated . We tested the hypothesis that quercetin supplementation reduces blood pressure in hypertensive patients . We then determined whether the antihypertensive effect of quercetin is associated with reductions in systemic oxidant stress . Men and women with prehypertension ( n = 19 ) and stage 1 hypertension ( n = 22 ) were enrolled in a r and omized , double-blind , placebo-controlled , crossover study to test the efficacy of 730 mg quercetin/d for 28 d vs. placebo . Blood pressure ( mm Hg , systolic/diastolic ) at enrollment was 137 + /- 2/86 + /- 1 in prehypertensives and 148 + /- 2/96 + /- 1 in stage 1 hypertensive subjects . Blood pressure was not altered in prehypertensive patients after quercetin supplementation . In contrast , reductions in ( P < 0.01 ) systolic ( -7 + /- 2 mm Hg ) , diastolic ( -5 + /- 2 mm Hg ) , and mean arterial pressures ( -5 + /- 2 mm Hg ) were observed in stage 1 hypertensive patients after quercetin treatment . However , indices of oxidant stress measured in the plasma and urine were not affected by quercetin . These data are the first to our knowledge to show that quercetin supplementation reduces blood pressure in hypertensive subjects . Contrary to animal-based studies , there was no quercetin-evoked reduction in systemic markers of oxidative stress In vitro studies show Hibiscus sabdariffa L. , an ingredient found in many herbal tea blends and other beverages , has antioxidant properties , and , in animal models , extracts of its calyces have demonstrated hypocholesterolemic and antihypertensive properties . Our objective in this study was to examine the antihypertensive effects of H. sabdariffa tisane ( hibiscus tea ) consumption in humans . A r and omized , double-blind , placebo-controlled clinical trial was conducted in 65 pre- and mildly hypertensive adults , age 30 - 70 y , not taking blood pressure (BP)-lowering medications , with either 3 240-mL servings/d of brewed hibiscus tea or placebo beverage for 6 wk . A st and ardized method was used to measure BP at baseline and weekly intervals . At 6 wk , hibiscus tea lowered systolic BP ( SBP ) compared with placebo ( -7.2 + /- 11.4 vs. -1.3 + /- 10.0 mm Hg ; P = 0.030 ) . Diastolic BP was also lower , although this change did not differ from placebo ( -3.1 + /- 7.0 vs. -0.5 + /- 7.5 mm Hg ; P = 0.160 ) . The change in mean arterial pressure was of borderline significance compared with placebo ( -4.5 + /- 7.7 vs. -0.8 + /- 7.4 mm Hg ; P = 0.054 ) . Participants with higher SBP at baseline showed a greater response to hibiscus treatment ( r = -0.421 for SBP change ; P = 0.010 ) . No effects were observed with regard to age , gender , or dietary supplement use . These results suggest daily consumption of hibiscus tea , in an amount readily incorporated into the diet , lowers BP in pre- and mildly hypertensive adults and may prove an effective component of the dietary changes recommended for people with these conditions BACKGROUND To evaluate health benefits attributed to Hibiscus sabdariffa L. a r and omized , open-label , two-way crossover study was undertaken to compare the impact of an aqueous H. sabdariffa L. extract ( HSE ) on the systemic antioxidant potential ( AOP ; assayed by ferric reducing antioxidant power ( FRAP ) ) with a reference treatment ( water ) in eight healthy volunteers . The biokinetic variables were the areas under the curve ( AUC ) of plasma FRAP , ascorbic acid and urate that are above the pre-dose concentration , and the amounts excreted into urine within 24 h ( Ae(0 - 24 ) ) of antioxidants as assayed by FRAP , ascorbic acid , uric acid , malondialdehyde ( biomarker for oxidative stress ) , and hippuric acid ( metabolite and potential biomarker for total polyphenol intake ) . RESULTS HSE caused significantly higher plasma AUC of FRAP , an increase in Ae(0 - 24 ) of FRAP , ascorbic acid and hippuric acid , whereas malondialdehyde excretion was reduced . Furthermore , the main hibiscus anthocyanins as well as one glucuronide conjugate could be quantified in the volunteers ' urine ( 0.02 % of the administered dose ) . CONCLUSION The aqueous HSE investigated in this study enhanced the systemic AOP and reduced the oxidative stress in humans . Furthermore , the increased urinary hippuric acid excretion after HSE consumption indicates a high biotransformation of the ingested HSE polyphenols , most likely caused by the colonic microbiota Considering the high prevalence of hypertension , its debilitating end organ damage , and the side effects of chemical drugs used for its treatment , we conducted this experimental study to evaluate the effect of sour tea ( Hibiscus sabdariffa ) on essential hypertension . For this purpose , 31 and 23 patients with moderate essential hypertension were r and omly assigned to an experimental and control group , respectively . Patients with secondary hypertension or those consuming more than two drugs were excluded from the study . Systolic and diastolic blood pressures were measured before and 15 days after the intervention . In the experimental group , 45 % of the patients were male and 55 % were female , and the mean age was 52.6 + /- 7.9 years . In the control group , 30 % of the patients were male , 70 % were female , and the mean age of the patients was 51.5 + /- 10.1 years . Statistical findings showed an 11.2 % lowering of the systolic blood pressure and a 10.7 % decrease of diastolic pressure in the experimental group 12 days after beginning the treatment , as compared with the first day . The difference between the systolic blood pressures of the two groups was significant , as was the difference of the diastolic pressures of the two groups . Three days after stopping the treatment , systolic blood pressure was elevated by 7.9 % , and diastolic pressure was elevated by 5.6 % in the experimental and control groups . This difference between the two groups was also significant . This study proves the public belief and the results of in vitro studies concerning the effects of sour tea on lowering high blood pressure . More extensive studies on this subject are needed Obesity is associated with a great diversity of diseases including non-alcoholic fatty liver disease . Our previous report suggested that Hibiscus sabdariffa extracts ( HSE ) had a metabolic-regulating and liver-protecting potential . In this study , we performed a clinical trial to further confirm the effect of HSE . Subjects with a BMI ≧ 27 and aged 18 - 65 , were r and omly divided into control ( n = 17 ) and HSE-treated ( n = 19 ) groups , respectively , for 12 weeks . Our data showed that consumption of HSE reduced body weight , BMI , body fat and the waist-to-hip ratio . Serum free fatty acid ( FFA ) was lowered by HSE . Anatomic changes revealed that HSE improved the illness of liver steatosis . Ingestion of HSE was well tolerated and there was no adverse effect during the trial . No alteration was found for serum α-amylase and lipase . The clinical effect should mainly be attributed to the polyphenols of HSE , since composition analysis showed that branched chain-amino acids , which is associated with obesity , is not obviously high . In conclusion , consumption of HSE reduced obesity , abdominal fat , serum FFA and improved liver steatosis . HSE could act as an adjuvant for preventing obesity and non-alcoholic fatty liver To compare the antihypertensive effectiveness of sour tea ( ST ; Hibiscus sabdariffa ) with black tea ( BT ) infusion in diabetic patients , this double-blind r and omized controlled trial was carried out . Sixty diabetic patients with mild hypertension , without taking antihypertensive or antihyperlipidaemic medic Output:	These effects were inversely associated with baseline BP values , and were robust in sensitivity analyses . This meta- analysis of RCTs showed a significant effect of H. sabdariffa in lowering both SBP and DBP .
MS22186	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objective : To examine the efficacy of a new device , which slows and regularises breathing , as a non-pharmacological treatment of hypertension and thus to evaluate the contribution of breathing modulation in the blood pressure ( BP ) reduction . Design and setting : R and omised , double-blind controlled study , carried out in three urban family practice clinics in Israel . Patients : Sixty-five male and female hypertensives , either receiving antihypertensive drug therapy or unmedicated . Four patients dropped out at the beginning of the study .Intervention : Self treatment at home , 10 minutes daily for 8 consecutive weeks , using either the device ( n = 32 ) , which guides the user towards slow and regular breathing using musical sound patterns , or a Walkman , with which patients listened to quiet music ( n = 29 ) . Medication was unchanged 2 months prior to and during the study period . Main outcome measures : Systolic BP , diastolic BP and mean arterial pressure ( MAP ) changes from baseline . Results : BP reduction in the device group was significantly greater than a predetermined ‘ clinical ly meaningful threshold ’ of 10.0 , 5.0 and 6.7 mm Hg for the systolic BP , diastolic BP and MAP respectively ( P = 0.035 , P = 0.0002 and P = 0.001 ) . Treatment with the device reduced systolic BP , diastolic BP and MAP by 15.2 , 10.0 and 11.7 mm Hg respectively , as compared to 11.3 , 5.6 and 7.5 mm Hg ( P = 0.14 , P = 0.008 , P = 0.03 ) with the Walkman . Six months after treatment had stopped , diastolic BP reduction in the device group remained greater than the ‘ threshold ’ ( P < 0.02 ) and also greater than in the walkman group ( P = 0.001 ) . Conclusions : The device was found to be efficacious in reducing high BP during 2 months of self-treatment by patients at home . Breathing pattern modification appears to be an important component in this reduction The purpose of the present study was to test the effectiveness of a cognitive-behavioral intervention as an adjunctive treatment of hypertension . To qualify for the study , subjects had to have an unmedicated clinic diastolic blood pressure > or = 95 mm Hg . After qualification , minimal drug requirements were established using a diuretic and a beta-blocker to control blood pressure at < or = 90 mm Hg . Subjects were then r and omized into a 6-week cognitive-behavioral intervention or a measurements -only control group . After the treatment phase , medication levels were reduced in all subjects by means of a systematic stepdown procedure . Subjects were followed for 1 year after the stepdown was completed . Addition of the cognitive-behavioral intervention was twice as effective as the control procedure in reducing drug requirements . At 12-months follow-up , 73 % of the treatment group were at lower levels of medication than at the time of r and omization , compared to 35 % in the control group . Moreover , 55 % of the treatment group remained completely free of medication , compared to 30 % of the control group , at the 12-month follow-up . The reductions in medication were associated with maintained controlled levels of clinic , ambulatory , and home blood pressure . The addition of a st and ardized and inexpensive group-administered cognitive-behavioral intervention to the drug treatment of hypertension is beneficial as an adjunctive treatment in reducing drug requirements for patients with hypertension , thereby reducing the costs and potential side effects of antihypertensive medications Thirty-three moderate hypertensives were converted to a 2-drug regimen of metoprolol and diuretic and BPs stabilized at a well-controlled level . They then completed one of three conditions over an 8-week interval : ( I ) 16 sessions of TBF ( h and and foot warming ) ; ( II ) 16 sessions of frontal EMG-BF ; ( III ) regular home monitoring of BP . Attempts were then made to withdraw the patients from the sympatholytic medication . Those successfully withdrawn were followed up for one year . There were no significant advantages for TBF over the other two conditions in the short term or with long-term follow-up . Only 27 % of treated patients ( including Condition III failures who were remedicated and treated with TBF ) were successfully off of the sympatholytic at a one-year follow-up . The generally poor results on clinical outcome were confirmed by clinic BPs , home BPs by patients , and 24-hour ambulatory BPs On screening 192 men and women aged 35 - 64 were identified as having two or more of the following risk factors : blood pressure greater than or equal to 140/90 mm Hg , plasma cholesterol concentration greater than or equal to 6.3 mmol/l ( 243.6 mg/100 ml ) , and current smoking habit greater than or equal to 10 cigarettes a day . They were r and omly allocated to a group for modification of behaviour or to serve as controls . Both groups were given health education leaflets containing advice to stop smoking , to reduce animal fats in the diet , and on the importance of reducing blood pressure . In addition , the treatment group had group sessions of one hour a week for eight weeks in which they were taught breathing exercises , relaxation , and meditation and about managing stress . It had previously been found that after eight weeks and eight months there was a significantly greater reduction in both systolic and diastolic blood pressures in the group taught to relax compared with the control group . After four years of follow up these differences in blood pressure were maintained . Plasma cholesterol concentration and the number of cigarettes smoked were lower in the treatment group at eight weeks and eight months but not at the four year follow up . At four years more subjects in the control group reported having had angina and treatment for hypertension and its complications . Incidence of ischaemic heart disease , fatal myocardial infa rct ion , or electrocardiographic evidence of ischaemia was significantly greater in the control group . If the results of this study could be obtained in a larger study the financial and health care implication s would be enormous & NA ; This industry‐based r and omized study compared the effects of behavioral treatment ( BT ) and blood pressure monitoring ( BPM ) on blood pressure ( BP ) change in 158 unmedicated persons with mild hypertension ( diastolic blood pressure 90 to 104 mm Hg ) . Participants recruited by a three‐stage screening were r and omly assigned to BT or BPM groups and stratified by entry diastolic blood pressure ( DBP ) , age , and sex . BT participants received relaxation training , with or without the addition of biofeedback , cognitive restructuring , and health behavior change components . During the study , all participants were followed by their usual care physicians and received medical advice . At 18 weeks into the study , after the BT groups completed training , both the BT and BPM groups showed significant reductions in systolic blood pressure ( SBP ) and DBP assessed in the company medical clinic ( 7.4 and 9.0 mm Hg SBP and 4.5 and 5.9 mm Hg DBP , respectively ) . These reductions were maintained throughout the 36‐week follow‐up period . Reductions in BP assessed at the participants ' worksite were similar for BT and BPM participants throughout most of the trial , indicating little advantage to the inclusion of behavioral interventions over monitoring alone . Differences in BP changes observed among participants receiving various combinations of behavioral treatment components indicated that the cognitive restructuring component reduced SBP in the worksite by an additional 5.4 mm Hg ( p less than 0.05 ) . Possible explanations for the BP changes observed in the BPM group and implication s of the results for the treatment of unmedicated mild hypertensives are discussed The present study compared the effectiveness of three procedures in the treatment of 34 individuals with essential hypertension : ( 1 ) stress management training plus relaxation imagery , which consisted of an adaptation of existing stress management techniques in conjunction with extensive relaxation training using relaxation imagery ; ( 2 ) relaxation imagery alone ; and ( 3 ) weekly blood pressure checks . The relaxation imagery technique involved visualization of a relaxing image along with concentration on suggestions of relaxation , heaviness , and warmth . Treatment was individualized and lasted 8 weeks . Results indicated stress management plus relaxation imagery and relaxation imagery alone were significantly more effective than blood pressure checks in reducing systolic and diastolic blood pressures during treatment and in maintaining diastolic blood pressure reductions during follow-up . However , no significant differences were found between the two treatment procedures . Clinical implication s of these findings are discussed BACKGROUND To our knowledge , no single investigation concerning the long-term effects of overweight status on the risk for hypertension , hypercholesterolemia , diabetes mellitus , and cardiovascular sequelae has been reported . METHODS Relations between categories of body mass index ( BMI ) , cardiovascular disease risk factors , and vascular disease end points were examined prospect ively in Framingham Heart Study participants aged 35 to 75 years , who were followed up to 44 years . The primary outcome was new cardiovascular disease , which included angina pectoris , myocardial infa rct ion , coronary heart disease , or stroke . Analyses compared overweight ( BMI [ calculated as weight in kilograms divided by the square of height in meters ] , 25.0 - 29.9 ) and obese persons ( BMI > or = 30 ) to a referent group of normal-weight persons ( BMI , 18.5 - 24.9 ) . RESULTS The age-adjusted relative risk ( RR ) for new hypertension was highly associated with overweight status ( men : RR , 1.46 ; women : RR , 1.75 ) . New hypercholesterolemia and diabetes mellitus were less highly associated with excess adiposity . The age-adjusted RR ( confidence interval [ CI ] ) for cardiovascular disease was increased among those who were overweight ( men : 1.21 [ 1.05 - 1.40 ] ; women : 1.20 [ 1.03 - 1.41 ] ) and the obese ( men : 1.46 [ 1.20 - 1.77 ] ; women : 1.64 [ 1.37 - 1.98 ] ) . High population attributable risks were related to excess weight ( BMI > or = 25 ) for the outcomes hypertension ( 26 % men ; 28 % women ) , angina pectoris ( 26 % men ; 22 % women ) , and coronary heart disease ( 23 % men ; 15 % women ) . CONCLUSIONS The overweight category is associated with increased relative and population attributable risk for hypertension and cardiovascular sequelae . Interventions to reduce adiposity and avoid excess weight may have large effects on the development of risk factors and cardiovascular disease at an individual and population level Controlled studies have demonstrated that relaxation training can lead to significant in-clinic blood pressure ( BP ) reductions in patients with essential hypertension . We examined the BP-lowering effect of relaxation training during the working day . Forty-two patients being treated for essential hypertension with diastolic BPs greater than 90 mm Hg were r and omized into either a relaxation training program or no treatment . Multiple BP measurements were made during the working hours , using an ambulatory monitoring device , before and after training . Significant work-site differences between groups were evident after treatment both for systolic and diastolic pressures . These results suggest that relaxation therapy leads to a reduction in BP that is evident in the natural environment , providing new evidence that the procedure is a useful adjunct to the treatment of hypertensive patients & NA ; This article reports the findings of a study design ed to evaluate the long‐term effectiveness of an industry‐based relaxation training program in the treatment of hypertensives whose blood pressures were not well controlled by antihypertensive medication . Following a three‐stage screening process , 137 participants were r and omly allocated to either relaxation training ( RT ) or to blood pressure monitoring ( BPM ) at two worksites . Participants continued to receive medical care from their primary physicians during the course of the study . The advantage for participants receiving RT , in terms of mean blood pressure changes , was modest and of short duration . However , a larger proportion of participants in the RT group came into good control ( blood pressures below 90 mm Hg ) than in the BPM group following treatment ( 69.4 % vs 41.5 % , p less than 0.001 ) . This advantage continued to 24 months ' follow‐up ( 63.9 % vs 47.7 % , p less than 0.05 ) . At 30 months ' follow‐up there was no significant difference between the groups ( 75.0 % vs 70.8 % ) . Within‐group analyses revealed that the BPM group also achieved significant blood pressure lowering which was maintained during the study . The largest initial difference between the two groups was for individuals whose entry diastolic blood pressures were most out of control despite several years of pharmacologic treatment . No difference was found between the two groups in the prescription of antihypertensive medication Fifty-two pharmacologically treated hypertensive patients were r and omized to one of four treatment groups : ( 1 ) diastolic blood pressure biofeedback , ( 2 ) progressive deep muscle relaxation training , ( 3 ) self-directed relaxation training , or ( 4 ) medication alone . Data collection occurred during baseline , treatment , and 1-year follow-up phases in a laboratory , a medical clinic , and the patient 's own home . Patients from all four groups combined showed mean blood pressure reductions of −10.2/−5.5 mm Hg on clinic recordings and −2.4/−.7 mm Hg on home recordings , which were maintained throughout the follow-up period . There were no significant differences among the four groups in terms of blood pressure reduction . Patients given adjunctive behavioral treatment showed significantly larger reductions in medication usage compared to patients Output:	In terms of antihypertensive medication , no favorable effects of stress-reduction techniques could be identified .
MS22187	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Polyclonal intravenous IgG ( IVIG ) was administered as an infusion 6 times every 3 weeks ( week 0 , 3 , 6 , 9 , 12 , 15 ) in doses of 0.1 , 0.4 and 0.8 g/kg BW to determine the dose causing an increase in 12 pneumococcal antibody types above the protective level of 200 ng/ml of antibody N. The dose of 0.4 g/kg BW was found to be optimal in patients with chronic lymphocytic leukaemia ( CLL ) . From the first infusion onwards at least 80 % of CLL patients had increases in all 12 antibodies . Five weeks after the last infusion the antibody levels were still elevated in 80 % of patients with CLL . The dose of 0.8 g/kg raised all 12 antibodies in 53 - 73 % of CLL patients when assessment s were made after each infusion . In multiple myeloma ( MM ) patients , 73 - 82 % and 73 - 91 % of patients had increased antibody levels , respectively , before and after the 4th-6th infusions at the 0.8 g/kg dose level . However , in only 45 - 50 % of patients did the antibodies remain increased 2 weeks after the treatment at this dose . The dose of 0.4 g/kg caused antibody increases in only 30 - 50 % of patients when measured before the 4th-6th infusion . Serum IgG increased significantly only in the CLL patients , whereas in the MM patients it was high from the beginning owing to the disease . Therefore , the pneumococcal antibody levels were a better marker for the purpose of dose finding . The dosage recommendation in CLL is 0.4 g/kg every 3 weeks until week 12 , when steady state is reached . The maintenance dose is 0.4 g/kg every 5 weeks . In MM patients , who have a faster elimination rate of antibodies , the recommended loading dose is 0.8 g/kg , followed by 0.4 g/kg every week as a continuous treatment . Treatment with IVIG in CLL and MM was generally well tolerated . Only 25 % of patients experienced minor side-effects , the most frequent being febrile reactions , shivering and headache Patients treated with allogeneic bone marrow transplantation ( BMT ) suffer from a deficient humoral immunity during the post-transplant period . To prevent infections patients may receive prophylactic intravenous immunoglobulin ( IVIG ) therapy from 1 week before to 3 months after BMT . We have studied the effect of IVIG treatment on reconstitution of immunoglobulin repertoires in transplanted patients . Sera obtained from 13 IVIG-treated and 31 non-IVIG-treated patients before and at different time points after BMT , ranging from 3 days to 3 years , and from 18 healthy controls , were analyzed using a quantitative immunoblot system . The average immunoglobulin (Ig)M and IgG reactivity profiles against antigens derived from human liver , muscle and skin as well as Staphylococcus epidermidis protein extracts were similar in both patient groups and in controls . Both IgG and IgM reactivity profiles are , however , less heterogeneous among the individuals in the IVIG-treated patient group . Around 1 year after BMT the heterogeneity of the IgM reactivity profiles against allogeneic protein extracts is much lower in the IVIG-treated group compared to the non-IVIG-treated group and the healthy controls . This effect remains months to years after the IVIG treatment has been completed . Our results suggest that IVIG influences selection of the natural antibody repertoire mediated by the variable (V)-region during reconstitution after BMT To determine whether intravenous immunoglobulin ( IVIg ) given monthly from day 90 to day 360 posttransplantation decreased the incidence of late infection , chronic graft-vs.-host disease ( GVHD ) , and obliterative bronchiolitis after marrow transplantation , patients were assigned r and omly to receive either IVIg ( 500 mg/kg/month ) or no IVIg prophylaxis . Participants were registered before transplantation , and 250 patients ( 123 IVIg and 127 control ) were evaluable for events after day 100 . The two groups were balanced for age , marrow source , cytomegalovirus ( CMV ) seropositivity , pretransplantation conditioning , and prophylaxis for infection and GVHD . Between days 100 and 365 posttransplantation , the incidence of bacteremia or septicemia per 100 patient-days of risk was 0.10 in the IVIg group and 0.12 in the controls ( p = not significant ) . During the same period , the incidence of localized infection was marginally higher in control patients than in IVIg recipients ( 0.44 vs. 0.24 , respectively ; relative risk [ RR ] 1.46 , p < 0.07 ) . Administration of IVIg prophylaxis had no effect on survival , the incidence of obliterative bronchiolitis , severity of airflow obstruction , or the incidence or mortality of chronic GVHD . After discontinuing IVIg prophylaxis at day 360 , subsequent recovery of endogeneous humoral immunity was impaired ( serum IgG1 and IgA levels were significantly lower than controls at day 730 ) , and total infections were less common in the second year in control patients than in former IVIg recipients ( 0.12 vs 0.19 , respectively ; RR 0.61 , p = 0.03 ) . We conclude that in the absence of hypogammaglobulinemia , monthly administration of IVIg given from day 90 to 360 does not reduce late complications and may impair long-term humoral immune recovery after marrow transplantation In a study of 63 allogeneic and autologous bone marrow transplants , patients were r and omized to receive the IgM and IgA enriched intravenous immunoglobulin ( IVIG ) preparation ( Pentaglobin ) . Pentaglobin has been postulated to have anti-endotoxin properties and one of the aims of the study was to measure endotoxin levels in these patients together with the clinical sequelae of infection . The anti-endotoxin effects of Pentaglobin were found to reside in the IgM fraction . Those patients who received Pentaglobin were significantly protected from dying from infection in the first 100 days after the transplant , although it was not actually possible to document bacterial infections as the cause of death in the control patients . Peak endotoxin levels were significantly reduced ( p = 0.02 ) in those patients receiving Pentaglobin . Liver damage as assessed by liver enzyme abnormalities correlated significantly with the presence of endotoxaemia greater than 25 pg/ml and up to 70 % of pyrexial episodes were associated with endotoxaemia . Our results suggest that Pentaglobin is useful in reducing hepatic toxicity and this may be related to a reduction in endotoxaemia Overwhelming infections cause significant morbidity and mortality in the immunocompromised host . There is considerable in vitro and in vivo evidence that the immune deficient state which accompanies acute leukaemia , and , is exacerbated by intensive chemotherapy , contributes to the infection risk in these patients . The most easily documented and corrected is that of impaired humoral immunity . In order to study the clinical significance of the deficit a double blind , r and omised , placebo controlled pilot study was set up design ed to test the feasibility , efficacy and toxicity of using prophylactic intravenous immunoglobulin to prevent infective complications in this patient group . Patients received 150 mg/kg of Pentaglobin , an immunoglobulin preparation specifically enriched in IgM and IgA , on days 0 , 10 and 20 of the chemotherapy regimes . There were no adverse side effects . Patients in the placebo group had a 25 % fall in IgM level whilst IgG and IgA remained unchanged . The treatment group maintained a stable IgM and IgG concentration throughout but had a rise in IgA. There was no difference in the total number of septicaemic episodes in each group but the placebo group had an increased number of non Staphylococcal infections ( P < 0.04 ) . We conclude that intravenous Pentaglobin protects patients against a fall in IgM during induction chemotherapy for acute leukaemia and decreases the number of non Staphylococcal infections A r and omized crossover study of prophylactic immunoglobulin ( IgG ) therapy was performed in patients with chronic lymphocytic leukaemia ( CLL ) or non-Hodgkin 's lymphoma ( NHL ) . Twelve patients with hypogammaglobulinemia or a history of recurrent infections received infusions of IgG or placebo intravenously ( IV ) every 3 weeks for 1 year . They were then switched to the alternative preparation for another year . The number of serious bacterial infections was significantly less ( P = .001 ; Mainl and 's cross-over method ) in the months in which patients received IgG. Serious bacterial infections showed a trend to be associated with an IgG level less than 6.4 g/L ( P = .046 ; Fisher 's exact test ) Forty-two patients with chronic lymphocytic leukaemia ( CLL ) , serum IgG levels < 5.5 milligrams and a history of two or more recent infections , were r and omized to receive infusions of 18 g human intravenous immunoglobulin ( IVIg ) or human albumin placebo every three weeks . During the 12 month study 122 infections were documented but only four were associated with neutropenia . Ten patients ( 24 % ) with IgG levels < 3.0 milligrams experienced 65 % of the infections . In response to IVIg there were immediate and accumulative increases in serum IgG levels and an associated decrease in total and serious infections . If three further infections occurred , placebo patients were commenced on 18 g IVIg , and IVIg patients were increased to 24 g IVIg . Approximately 50 % of these cases subsequently remained infection free . The study shows the usefulness of prophylactic S and oglobulin in CLL patients with hypogammaglobulinaemia , and suggests that this may be justified in those with recurrent infections and serum IgG levels < 3 milligrams Treatment with intense myelosuppressive therapy ( including bone marrow transplantation ) has improved survival in patients with various malignant neoplasms [ 1 , 2 ] . Unfortunately , this treatment increases the incidence of infectious complications , primarily during the period of myelosuppression [ 3 ] . Various methods have been used to limit infection during myelosuppression [ 4 - 7 ] . Despite these pre caution s , bacteremia and fungemia continue to occur in at least one third of patients with sustained neutropenia . Intravenous immunoglobulin ( IVIG ) therapy prevents infections in patients with inborn B-cell deficiencies and hypogammaglobulinemia secondary to hematologic disorders such as chronic lymphocytic leukemia [ 8 - 10 ] . Intravenous immunoglobulin has also been used successfully to treat immune thrombocytopenic purpura , alloimmunity to platelets , and other immune-mediated disorders by a mechanism of immune system modulation [ 11 ] . After allogeneic bone marrow transplantation , IVIG is commonly used to prevent graft-versus-host disease [ 12 ] . During these bone marrow transplant trials , a reduction in bacterial infection was also observed in patients who were not necessarily hypogammaglobulinemic . This finding was initially reported in small anecdotal series but was later confirmed by large prospect i ve studies [ 12 - 17 ] . This effect of IVIG was observed during the pre-engraftment ( neutropenic ) and myelosuppression recovery phases . Most patients in these studies were undergoing allogeneic bone marrow transplantation , for which graft-versus-host disease and its treatment contribute to the rate of infection [ 18 ] . Intravenous immunoglobulin is not routinely used during autologous bone marrow transplantation or severely myelosuppressive therapy because prevention of graft-versus-host disease is unnecessary . Because IVIG prevents infection after allogeneic bone marrow transplantation , it might also do so in other patients undergoing intense myelosuppression and thus may serve as a general prophylactic agent for infections . Intravenous immunoglobulin is expensive and thus should not be used indiscriminately . We design ed a prospect i ve study that r and omized patients who were expected to develop severe and sustained myelosuppression to receive IVIG or no treatment . We specifically wished to determine whether IVIG could reduce the incidence of severe infections in patients with neutropenia but without allogeneic cofactors such as graft-versus-host disease . We therefore sought to determine whether the benefits of IVIG after allogeneic bone marrow transplantation occur as a direct effect of the drug or as an indirect result of a reduced incidence of graft-versus-host disease . Methods Study Design We conducted a stratified , r and omized comparison of patients who either underwent autologous bone marrow transplantation or received substantial myelosuppressive therapy for acute leukemia or other malignant conditions . The protocol and consent forms were approved by the Institutional Review Boards of the three participating institutions : Baylor University Medical Center , Dallas , Texas ; The University of Louisville , Louisville , Kentucky ; and V and erbilt University , Nashville , Tennessee . Patients were stratified for treatment ( autologous bone marrow transplantation or Output:	CMV infections were not significantly reduced with either polyvalent IVIG or CMV-IVIG . Interstitial pneumonitis was reduced with polyvalent IVIG in older studies but not in the more recent ones , nor in studies assessing CMV-IVIG . Because there is no advantage in terms of survival or infection prevention , IVIG does not have a role in HSCT
MS22188	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To examine the antiviral potency and tolerability profile of a single-class four drug ( quadruple ) nucleoside reverse transcriptase inhibitor ( NRTI ) regimen compared with a 2-class st and ard-of-care regimen . METHODOLOGY A three-centre , r and omized , open-label comparative pilot study of zidovudine/lamivudine/efavirenz ( triple ) versus abacavir/lamivudine/zidovudine/tenofovir ( quadruple ) therapy in HIV-1-infected , treatment-naive individuals . Both regimens were taken without regard to food and consisted of a twice-daily regimen and 3 pills/day . The study power was based on time-weighted average changes in HIV-1 RNA load . RESULTS A total of 114 individuals ( 56 triple , 57 quadruple ) received at least one dose of medication . Patients were well matched at baseline for viral load ( mean 5.26 log10 versus 5.13 log10 , respectively ) and CD4 cell count ( median 193 versus 153 cells/mm3 , respectively ) . The two regimens performed similarly with regards to all endpoints . At week 48 , by intention-to-treat , missing = failure analysis , 68 % of triple- and 67 % of quadruple-drug treated patients had an HIV-1 RNA < 50copies/ml ( P>0.05 ) . On-treatment analysis showed 40/40 ( 100 % ) of triple- and 39/40 ( 97.5 % ) of quadruple-drug treated patients ( P=0.996 ) had responded to < 50copies/ml . No unexpected adverse events were reported . Changes in total cholesterol and triglycerides were modest but significantly favoured the quadruple therapy regimen at multiple time points . CONCLUSION This pilot study suggests a quadruple NRTI-based regimen provides similar antiviral potency , tolerability and administrative characteristics to a 2-class triple therapy regimen . These findings should be confirmed in a more fully powered study . Potent quadruple NRTI-based regimens may have advantages for some individuals with regards to salvageability , tolerability and drug interactions CONTEXT Abacavir , a nucleoside analogue , has demonstrated suppression of human immunodeficiency virus ( HIV ) replication alone and in combination therapy . However , the role of abacavir in a triple nucleoside combination regimen has not been evaluated against a st and ard protease inhibitor-containing regimen for initial antiretroviral treatment . OBJECTIVE To evaluate antiretroviral equivalence and safety of an abacavir-lamivudine-zidovudine regimen compared with an indinavir-lamivudine-zidovudine regimen . DESIGN AND SETTING A multicenter , phase 3 , r and omized , double-blind trial with an enrollment period from August 1997 to June 1998 , with follow-up through 48 weeks at 73 clinical research units in the United States , Canada , Australia , and Europe . PATIENTS Five hundred sixty-two antiretroviral-naive , HIV-infected adults with a plasma HIV RNA level of at least 10 000 copies/mL and a CD4 cell count of at least 100 x 10(6)/L. INTERVENTIONS Patients were stratified by baseline HIV RNA level and r and omly assigned to receive a combination tablet containing 150 mg of lamivudine and 300 mg of zidovudine twice daily plus either 300 mg of abacavir twice daily and indinavir placebo or 800 mg of indinavir every 8 hours daily plus abacavir placebo . After 16 weeks , patients with confirmed HIV RNA levels greater than 400 copies/mL were eligible to continue receiving r and omized treatment or receive open-label therapy . MAIN OUTCOME MEASURE Virologic suppression , defined as HIV RNA concentration of 400 copies/mL or less at week 48 . RESULTS The proportion of patients who met the end point of having an HIV RNA level of 400 copies/mL or less at week 48 was equivalent in the abacavir group ( 51 % [ 133/262 ] ) and in the indinavir group ( 51 % [ 136/265 ] ) with a treatment difference of -0.6 % ( 95 % confidence interval [ CI ] , -9 % to 8 % ) . In patients with baseline HIV RNA levels greater than 100 000 copies/mL , the proportion of patients achieving less than 50 copies/mL was greater in the indinavir group than in the abacavir group with 45 % ( 45/100 ) vs 31 % ( 30/96 ) and a treatment diference of -14 % ( 95 % CI , -27 % to 0 % ) . The 2 treatments were comparable with respect to their effects on CD4 cell count . There was no difference between groups in the frequency of treatment-limiting adverse events or laboratory abnormalities . One death in the abacavir group was attributed to hypersensitivity reaction , which occurred following rechallenge with abacavir , approximately 3 weeks after initiating study treatment . CONCLUSIONS In this study of antiretroviral-naive HIV-infected adults , the triple nucleoside regimen of abacavir-lamivudine-zidovudine was equivalent to the regimen of indinavir-lamivudine-zidovudine in achieving a plasma HIV RNA level of less than 400 copies/mL at 48 weeks BACKGROUND The most effective highly active antiretroviral therapy ( HAART ) to prevent mother-to-child transmission of human immunodeficiency virus type 1 ( HIV-1 ) in pregnancy and its efficacy during breast-feeding are unknown . METHODS We r and omly assigned 560 HIV-1-infected pregnant women ( CD4 + count , > or = 200 cells per cubic millimeter ) to receive coformulated abacavir , zidovudine , and lamivudine ( the nucleoside reverse-transcriptase inhibitor [ NRTI ] group ) or lopinavir-ritonavir plus zidovudine-lamivudine ( the protease-inhibitor group ) from 26 to 34 weeks ' gestation through planned weaning by 6 months post partum . A total of 170 women with CD4 + counts of less than 200 cells per cubic millimeter received nevirapine plus zidovudine-lamivudine ( the observational group ) . Infants received single-dose nevirapine and 4 weeks of zidovudine . RESULTS The rate of virologic suppression to less than 400 copies per milliliter was high and did not differ significantly among the three groups at delivery ( 96 % in the NRTI group , 93 % in the protease-inhibitor group , and 94 % in the observational group ) or throughout the breast-feeding period ( 92 % in the NRTI group , 93 % in the protease-inhibitor group , and 95 % in the observational group ) . By 6 months of age , 8 of 709 live-born infants ( 1.1 % ) were infected ( 95 % confidence interval [ CI ] , 0.5 to 2.2 ) : 6 were infected in utero ( 4 in the NRTI group , 1 in the protease-inhibitor group , and 1 in the observational group ) , and 2 were infected during the breast-feeding period ( in the NRTI group ) . Treatment-limiting adverse events occurred in 2 % of women in the NRTI group , 2 % of women in the protease-inhibitor group , and 11 % of women in the observational group . CONCLUSIONS All regimens of HAART from pregnancy through 6 months post partum result ed in high rates of virologic suppression , with an overall rate of mother-to-child transmission of 1.1 % . ( Clinical Trials.gov number , NCT00270296 . BACKGROUND We investigated virological response and the emergence of resistance in the Nevirapine or Abacavir ( NORA ) sub study of the Development of Antiretroviral Treatment in Africa ( DART ) trial . METHODS Six hundred symptomatic antiretroviral-naive human immunodeficiency virus (HIV)-infected adults ( CD4 cell count , < 200 cells/mm(3 ) ) from 2 Ug and an centers were r and omized to receive zidovudine-lamivudine plus abacavir or nevirapine . Virology was performed retrospectively on stored plasma sample s at selected time points . In patients with HIV RNA levels > 1000 copies/mL , the residual activity of therapy was calculated as the reduction in HIV RNA level , compared with baseline . RESULTS Overall , HIV RNA levels were lower in the nevirapine group than in the abacavir group at 24 and 48 weeks ( P < .001 ) , although no differences were observed at weeks 4 and 12 . Virological responses were similar in the 2 treatment groups for baseline HIV RNA level < 100,000 copies/mL. The mean residual activity at week 48 was higher for abacavir in the presence of the typically observed resistance pattern of thymidine analogue mutations ( TAMs ) and M184V ( 1.47 log(10 ) copies/mL ) than for nevirapine with M184V and nonnucleoside reverse-transcriptase inhibitor mutations , whether accompanied by TAMs ( 0.96 log(10 ) copies/mL ) or not ( 1.18 log(10 ) copies/mL ) . CONCLUSIONS There was more extensive genotypic resistance in both treatment groups than is generally seen in re source -rich setting s. However , significant residual activity was observed among patients with virological failure , particularly those receiving zidovudine-lamivudine plus abacavir Objective To compare the safety/tolerability of abacavir and nevirapine in HIV-infected adults starting antiretroviral ( ARV ) therapy in Ug and a. Methods Twenty-four-week r and omized double-blind trial conducted with 600 symptomatic ARV-naive adults with CD4 < 200 cells/mm3 allocated to zidovudine/lamivudine plus 300 mg abacavir ( A ) and nevirapine placebo ( n = 300 ) or 200 mg nevirapine ( N ) and abacavir placebo ( n = 300 ) twice daily . The primary endpoint was any serious adverse event ( SAE ) definitely/probably or uncertain whether related to blinded nevirapine/abacavir . Secondary endpoints were adverse events leading to permanent discontinuation of blinded nevirapine/abacavir , and grade 4 events . Results Seventy-two per cent participants were women ; 19 % had WHO stage 4 disease ; the median age was 37 years ( range 18–66 ) ; the median baseline CD4 count was 99 cells/mm3 ( 1–199 ) . Ninety-five per cent completed 24 weeks : 4 % died and 1 % were lost to follow-up . Thirty-seven SAEs occurred on blinded drug in 36 participants . Twenty events [ 6 ( 2.0 % ) abacavir , 14 ( 4.7 % ) nevirapine participants ] were considered serious adverse reactions definitely/probably/uncertain whether related to blinded abacavir/nevirapine [ HR = 0.42 ( 95 % CI 0.16–1.09 ) P = 0.06 ] . Only 2.0 % of abacavir participants [ six patients ( 0.7–4.3 % ) ] experienced a suspected hypersensitivity reaction ( HSR ) . In total 14 ( 4.7 % ) abacavir and 30 ( 10.0 % ) nevirapine participants discontinued blinded abacavir/nevirapine ( P = 0.02 ) : because of toxicity ( 6A , 15N ; P = 0.07 , all rash/possible HSR and /or hepatotoxicity ) , anti-tuberculosis therapy ( 6A , 13N ) , or for other reasons ( 2A , 2N ) . Conclusions There was a trend towards a lower rate of serious adverse reactions in Ug and an adults with low CD4 starting ARV regimens with abacavir than with nevirapine . This suggests that abacavir could be used more widely in re source -limited setting s without major safety concerns Background Hyperlipidemia secondary to protease inhibitors ( PI ) may abate by switching to anti-HIV medications without lipid effects . Method An open-label , r and omized pilot study compared changes in fasting lipids and HIV-1 RNA in 104 HIV-infected adults with PI-associated hyperlipidemia ( fasting serum total cholesterol > 200 mg/dL ) who were r and omized either to a regimen in which their PI was replaced by abacavir 300 mg twice daily ( n = 52 ) or a regimen in which their PI was continued ( n = 52 ) for 28 weeks . All patients had undetectable viral loads ( HIV-1 RNA < 50 copies/mL ) at baseline and were naïve to abacavir and non-nucleoside reverse transcript Output:	Switching improved serum lipids significantly . Of the studied triple-NRTI combinations only abacavir/lamivudine/zidovudine was sufficiently potent . Triple-NRTI maintenance after successful induction with two-class cART appeared successful in treatment-naive subjects and remains a useful option in specific circumstances , especially when other drugs are not available or drug interactions are an issue
MS22189	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Transtibial amputees encounter stairs and steps during their daily activities . The excessive pressure between residual limb/socket may reduce the walking capability of transtibial prosthetic users during ascent and descent on stairs . The purpose s of the research were to evaluate the interface pressure between Dermo ( shuttle lock ) and Seal-In X5 ( prosthetic valve ) interface systems during stair ascent and descent , and to determine their satisfaction effects on users . METHODS Ten amputees with unilateral transtibial amputation participated in the study . Interface pressure was recorded with F-socket transducer ( 9811E ) during stair ascent and descent at self-selected speed . Each participant filled in a question naire about satisfaction and problems encountered with the use of the two interface systems . FINDINGS The result ant mean peak pressure ( kPa ) was significantly lower for the Dermo interface system compared to that of the Seal-In X5 interface system at the anterior , posterior and medial regions during stair ascent ( 63.14 vs. 80.14 , 63.14 vs. 90.44 , 49.21 vs. 66.04 , respectively ) and descent ( 67.11 vs. 80.41 , 64.12 vs. 88.24 , 47.33 vs. 65.11 , respectively ) . Significant statistical difference existed between the two interface systems in terms of satisfaction and problems encountered ( P<0.05 ) . INTERPRETATION The Dermo interface system caused less pressure within the prosthetic socket compared to the Seal-In X5 interface system during stair negotiation . The qualitative survey also showed that the prosthesis users experienced fewer problems and increased satisfaction with the Dermo interface system OBJECTIVE To investigate the effects of 3 dissimilar suspension systems on participants ' satisfaction and perceived problems with their prostheses . DESIGN Question naire survey . SETTING A medical and engineering research center and a university biomedical engineering department . PARTICIPANTS Persons with unilateral transtibial amputation ( N=243 ) , using prostheses with polyethylene foam liner , silicone liner with shuttle lock , and seal-in liner . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Descriptive analyses were performed on the demographic information , satisfaction , and prosthesis-related problems of the study participants . RESULTS The results showed significant differences between the 3 groups regarding the degree of satisfaction and perceived problems with the prosthetic device . Analyses of the individual items revealed that the study participants were more satisfied with the seal-in liner and experienced fewer problems with this liner . The silicone liner with shuttle lock and seal-in liner users reported significant differences in maintenance time compared with the polyethylene foam liner . Users of the silicone liner with shuttle lock experienced more sweating , while those who used the seal-in liner had greater problems with donning and doffing the device . CONCLUSIONS The results of the survey provide a good indication that prosthetic suspension is improved with the seal-in liner as compared with the polyethylene foam liner and silicone liner with shuttle lock . However , further prospect i ve studies are needed to investigate which system provides the most comfort and the least problems for participants Background The suction sockets that are commonly prescribed for transtibial amputees are believed to provide a better suspension than the pin/lock systems . Nevertheless , their effect on amputees ’ gait performance has not yet been fully investigated . The main intention of this study was to underst and the potential effects of the Seal-in ( suction ) and the Dermo ( pin/lock ) suspension systems on amputees ’ gait performance . Methodology /Principal Findings Ten unilateral transtibial amputees participated in this prospect i ve study , and two prostheses were fabricated for each of them . A three-dimensional motion analysis system was used to evaluate the temporal-spatial , kinematics and kinetics variables during normal walking . We also asked the participants to complete some part of Prosthesis Evaluation Question naire ( PEQ ) regarding their satisfaction and problems with both systems . The results revealed that there was more symmetry in temporal-spatial parameters between the prosthetic and sound limbs using the suction system . However , the difference between two systems was not significant ( p<0.05 ) . Evaluation of kinetic data and the subjects ’ feedback showed that the participants had more confidence using the suction socket and the sockets were more fit for walking . Nevertheless , the participants had more complaints with this system due to the difficulty in donning and doffing . Conclusion It can be concluded that even though the suction socket could create better suspension , fit , and gait performance , overall satisfaction was higher with the pin/lock system due to easy donning and doffing of the prosthesis . Trial Registration i rct .ir I RCT For this r and omized crossover trial , we compared two common transtibial socket suspension systems : the Alpha liner with distal locking pin and the Pe-Lite liner with neoprene suspension sleeve . Our original hypotheses asserted that increased ambulatory activity , wear time , comfort , and satisfaction would be found with the elastomeric suspension system . Thirteen subjects completed the study . Following 2.5-month accommodation to each condition , ambulatory activity was recorded ( steps/minute for 2 weeks ) , and subjects completed three question naires specific to prosthesis use and pain : the Prosthesis Evaluation Question naire ( PEQ ) , a Brief Pain Inventory ( BPI ) excerpt , and the Socket Comfort Score ( SCS ) . Upon completion , subjects selected their favored system for continued use . Ten subjects preferred the Pe-Lite and three the Alpha . Subjects spent 82 % more time wearing the Pe-Lite and took 83 % more steps per day . Ambulatory intensity distribution did not differ between systems . No statistically significant differences were found in question naire results . Subject feedback for each system was both positive and negative BACKGROUND The interface pressure between the residual limb and prosthetic socket has a significant effect on an amputee 's satisfaction and comfort . Liners provide a comfortable interface by adding a soft cushion between the residual limb and the socket . The Dermo and the Seal-In X5 liner are two new interface systems and , due to their relative infancy , very little are known about their effect on patient satisfaction . The aim of this study was to compare the interface pressure with these two liners and their effect on patient satisfaction . METHODS Nine unilateral transtibial amputees participated in the study . Two prostheses were fabricated for each amputee , one with the Seal-In liner and one with the Dermo liner . Interface pressure was measured at the anterior , posterior , medial and lateral regions during walking on the level ground . Each subject filled in a Prosthetic Evaluation Question naire ( PEQ ) regarding the satisfaction with the two liners . Findings The mean peak pressures with the Seal-In liner was 34.0 % higher at the anterior , 24.0 % higher at the posterior and 7.0 % higher at the medial regions of the socket ( P=0.008 , P=0.046 , P=0.025 ) than it was with the Dermo Liner . There were no significant differences in the mean peak pressures between the two liners at the lateral regions . In addition , significant difference was found between the two liners both for satisfaction and problems ( P<0.05 ) . Interpretation There was less interface pressure between the socket and the residual limb with the Dermo liner . The results indicated that the Dermo liner provides more comfort in the socket than the Seal-In liner OBJECTIVE To investigate the effect of a vacuum-assisted socket suspension system as compared with pin suspension on lower extremity amputees . DESIGN R and omized crossover with 3-week acclimation . SETTING Household , community , and laboratory environments . PARTICIPANTS Unilateral , transtibial amputees ( N=20 enrolled , N=5 completed ) . INTERVENTIONS ( 1 ) Total surface-bearing socket with a vacuum-assisted suspension system ( VASS ) , and ( 2 ) modified patellar tendon-bearing socket with a pin lock suspension system . MAIN OUTCOME MEASURES Activity level , residual limb volume before and after a 30-minute treadmill walk , residual limb pistoning , and Prosthesis Evaluation Question naire . RESULTS Activity levels were significantly lower while wearing the vacuum-assisted socket suspension system than the pin suspension ( P=.0056 ; 38,000 ± 9,000 steps per 2 wk vs 73,000 ± 18,000 steps per 2 wk , respectively ) . Residual limb pistoning was significantly less while wearing the vacuum-assisted socket suspension system than the pin suspension ( P=.0021 ; 1 ± 3 mm vs 6 ± 4 mm , respectively ) . Treadmill walking had no effect on residual limb volume . In general , participants ranked their residual limb health higher , were less frustrated , and cl aim ed it was easier to ambulate while wearing a pin suspension compared with the VASS . CONCLUSIONS The VASS result ed in a better fitting socket as measured by limb movement relative to the prosthetic socket ( pistoning ) , although the clinical relevance of the small but statistically significant difference is difficult to discern . Treadmill walking had no effect , suggesting that a skilled prosthetist can control for daily limb volume fluctuations by using conventional , nonvacuum systems . Participants took approximately half as many steps while wearing the VASS which , when coupled with their subjective responses , suggests a preference for the pin suspension system Objective The objectives of this study were to compare the effects of a newly design ed magnetic suspension system with that of two existing suspension methods on pistoning inside the prosthetic socket and to compare satisfaction and perceived problems among transtibial amputees . Design In this prospect i ve study , three lower limb prostheses with three different suspension systems were fabricated for ten transtibial amputees . The participants used each of the three prostheses for 1 mo in r and om order . Pistoning inside the prosthetic socket was measured by motion analysis system . The Prosthesis Evaluation Question naire was used to evaluate satisfaction and perceived problems with each suspension system . Results The lowest pistoning motion was found with the suction system compared with the other two suspension systems ( P < 0.05 ) . The new suspension system showed peak pistoning values similar to that of the pin lock system ( P = 0.086 ) . The results of the question naire survey revealed significantly higher satisfaction rates with the new system than with the other two systems in donning and doffing , walking , uneven walking , stair negotiation , and overall satisfaction ( P < 0.05 ) . Conclusions The new suspension system has the potential to be used as an alternative to the available suspension systems . The pistoning motion was comparable to that of the other two systems . The new system showed compatible prosthetic suspension with the other two systems ( suction and pin lock ) . The satisfaction with donning and doffing was high with the magnetic system . Moreover , the subjects reported fewer problems with the new system A clinical trial was conducted to evaluate the efficiency of ICEROSS on r and omly selected 46 male transtibial amputees . After rejection , only 27 ( 58.69 % ) amputees volunteered for various stages of the ICEROSS trial . All 27 were categorized into Group A-persons in employment ( n = 16 ) and Group B-persons out of employment or economically inactive ( n = 11 ) . The study was conducted on the basis of question naire information , clinical examination and objective tests . The pre- and post-ICEROSS status were compared between the groups . Group A was younger and did better . Trauma was the main cause of amputation . There were certain changes of the stump before and after ICEROSS . The amputees with ICEROSS suspension performed better and had improved mobility in Group A. At the workplace , dynamic activities were less than the static activities ( p < 0.001 ) and there were overall improvements in comfort and performance of amputees with ICEROSS Trans-tibial amputees with different indications for amputation often have stump problems . Many active amputees have limits in daily life and sports activities because of pressure ulcers , friction , allergic dermatitis or volume changes . Many methods and material s have been tried to make a well-fitted socket . A new polyurethane concept had been design ed with a shock absorbing effect . The purpose of this prospect i ve study was to compare a conventional suspension with a polyurethane concept with regard to the amputees ' satisfaction , socket comfort , physical capacity and to analyse the long-term effect . The total material includes 29 unilateral transtibial amputees . They answered a question naire after 2 months use of the polyurethane concept and were interviewed after 3 and 5 years . After 3 years 22 amputees and after 5 years 20 amputees used the polyurethane concept . Gait was registered in 7 amputees . Speed and symmetry index ( SI ) for temporal , stride and kinematics variables were used to evaluate gait . The amputees reported that the polyurethane concept was better or much better in physical capacity in 117 ( 67 % ) and socket comfort was better or much better in 119 ( 82 % ) compared with the conventional suspension . There was no obvious symmetry difference in gait variables in speed , step length , step time or single support or in kinematics knee variables . The amputees tended to walk faster , decrease in symmetry in temporal and stride variables and increase in symmetry in kinematics variables with the polyurethane concept . After 5 years 6 had died and 20 amputees of the surviving 23 used the polyurethane concept . Conclusions : The polyurethane concept increased comfort considerably and physical activity increased when the trans-tibial amputees changed from conventional suspension . Gait registration was not useful to evaluate the amputees ' satisfaction or socket comfort The ICEX ® system ( Ossur , Icel and ) , allows a socket to be manufactured directly onto the stump and is thought to provide improved comfort due to better pressure distribution whilst being easier to fit and manufacture . The aims of Output:	Conclusion : There is insufficient research to differentiate between the user experience of different transtibial liners . Clinical relevance The available evidence suggests that the user experience of commonly reported problems ( e.g. sweating ) may be very similar between different liners .
MS22190	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: CONTEXT A rigorous evaluation of continuous quality improvement ( CQI ) in medical practice has not been carried out on a national scale . OBJECTIVE To test whether low-intensity CQI interventions can be used to speed the national adoption of 2 coronary artery bypass graft ( CABG ) surgery process-of-care measures : preoperative beta-blockade therapy and internal mammary artery ( IMA ) grafting in patients 75 years or older . DESIGN , SETTING , AND PARTICIPANTS Three hundred fifty-nine academic and nonacademic hospitals ( treating 267 917 patients using CABG surgery ) participating in the Society of Thoracic Surgeons National Cardiac Data base between January 2000 and July 2002 were r and omized to a control arm or to 1 of 2 groups that used CQI interventions design ed to increase use of the process-of-care measures . INTERVENTION Each intervention group received measure-specific information , including a call to action to a physician leader ; educational products ; and periodic longitudinal , nationally benchmarked , site-specific feedback . MAIN OUTCOME MEASURE Differential incorporation of the targeted care processes into practice at the intervention sites vs the control sites , assessed by measuring preintervention ( January-December 2000)/postintervention ( January 2001-July 2002 ) site differences and by using a hierarchical patient-level analysis . RESULTS From January 2000 to July 2002 , use of both process measures increased nationally ( beta-blockade , 60.0%-65.6 % ; IMA grafting , 76.2%-82.8 % ) . Use of beta-blockade increased significantly more at beta-blockade intervention sites ( 7.3 % [ SD , 12.8 % ] ) vs control sites ( 3.6 % [ SD , 11.5 % ] ) in the preintervention/postintervention ( P = .04 ) and hierarchical analyses ( P<.001 ) . Use of IMA grafting also tended to increase at IMA intervention sites ( 8.7 % [ SD , 17.5 % ] ) vs control sites ( 5.4 % [ SD,15.8 % ] ) ( P = .20 and P = .11 for preintervention/postintervention and hierarchical analyses , respectively ) . Both interventions tended to have more impact at lower-volume CABG sites ( for interaction : P = .04 for beta-blockade ; P = .02 for IMA grafting ) . CONCLUSIONS A multifaceted , physician-led , low-intensity CQI effort can improve the adoption of care processes into national practice within the context of a medical specialty society infrastructure BACKGROUND The adherence to evidence -based treatment guidelines for acute myocardial infa rct ion ( AMI ) is still suboptimal . Therefore , we design ed a study to evaluate the effects of a collaborative quality improvement ( QI ) intervention on the adherence to AMI guidelines . The intervention used a national web-based quality registry to generate local and regular real-time performance feedback . METHODS A 12-month baseline measurement of the adherence rates was retrospectively collected , comprising the period July 1 , 2001 , through June 30 , 2002 . During the intervention period of November 1 , 2002 , through April 30 , 2003 , multidisciplinary teams from 19 nonr and omized intervention hospitals were subjected to a multifaceted QI-oriented intervention . Another 19 hospitals , unaware of their status as controls , were matched to the intervention hospitals . During the postintervention measurement period of May 1 , 2003 , through April 30 , 2004 , a total of 6726 consecutive patients were included at the intervention ( n = 3786 ) and control ( n = 2940 ) hospitals . The outcome measures comprised 5 Swedish national guideline -derived quality indicators , compared between baseline and postintervention levels in the control and QUICC intervention hospitals . RESULTS In the control and QI intervention hospitals , the mean absolute increase of patients receiving angiotensin-converting enzyme inhibitors was 1.4 % vs 12.6 % ( P = .002 ) , lipid-lowering therapy 2.3 % vs 7.2 % ( P = .065 ) , clopidogrel 26.3 % vs 41.2 % ( P = .010 ) , heparin/low-molecular weight heparin 5.3 % vs 16.3 % ( P = .010 ) , and coronary angiography 6.2 % vs 16.8 % ( P = .027 ) , respectively . The number of QI intervention hospitals reaching a treatment level of at least 70 % in 4 or 5 of the 5 indicators was 15 and 5 , respectively . In the control group , no hospital reached 70 % or more in just 4 of the 5 indicators . CONCLUSIONS By combining a systematic and multidisciplinary QI collaborative with a web-based national quality registry with functionality allowing real-time performance feedback , major improvements in the adherence to national AMI guidelines can be achieved Background — Adherence to evidence -based guidelines for treatment of stroke or transient ischemic attack is suboptimal . We sought to establish whether participation in Get With the Guidelines –Stroke was associated with improvements in adherence . Methods and Results — This prospect i ve , nonr and omized , national quality improvement program measured adherence to guideline recommendations in 322 847 hospitalized patients discharged with a diagnosis of ischemic stroke or transient ischemic attack . A volunteer sample of 790 US academic and community hospitals participated from 2003 through 2007 . The main outcome measures were change in adherence over time to 7 prespecified performance measures and a composite measure ( total number of interventions provided in eligible patients divided by total number of care opportunities among eligible patients ) . Generalized estimating equations were used to identify factors associated with improvement . Participation in Get With the Guidelines –Stroke was associated with improvements in the 7 individual and 1 composite measures from baseline to the fifth year : intravenous thrombolytics ( 42.09 % versus 72.84 % ) , early antithrombotics ( 91.46 % versus 97.04 % ) , deep vein thrombosis prophylaxis ( 73.79 % versus 89.54 % ) , discharge antithrombotics ( 95.68 % versus 98.88 % ) , anticoagulation for atrial fibrillation ( 95.03 % versus 98.39 % ) , lipid treatment for low-density lipoprotein > 100 mg/dL ( 73.63 % versus 88.29 % ) , smoking cessation ( 65.21 % versus 93.61 % ) , and composite ( 83.52 % versus 93.97 % ) ( P<0.0001 for all comparisons ) . Multivariate analysis showed that time in Get With the Guidelines –Stroke was associated with a 1.18-fold yearly increase in the odds of fulfilling care opportunities that was independent of secular trends . Conclusions — Get With the Guidelines –Stroke participation was associated with increased adherence to all stroke performance measures . Markedly improved stroke care was seen in all hospitals regardless of size , geography , and teaching status Background and Purpose — Limited information is available on stroke management in developing countries . An accurate monitoring of quality of stroke care will become crucial , particularly with the emerging paradigm of pay-for-performance . Our aim was to explore the feasibility of measuring st and ardized indicators of quality of ischemic stroke care in acute care facilities in Argentina . Methods — ReNACer is a prospect i ve , multicenter , countrywide , stroke registry comprising 74 academic and nonacademic institutions in Argentina . The registry includes patient-level information on demography , clinical characteristics , diagnostic procedures , treatment , and the selected key performance indicators of quality of ischemic stroke care ( access to thrombolysis or aspirin use in the acute setting , admission to design ated stroke units , length of stay , risk-adjusted in-hospital pneumonia , risk-adjusted in-hospital mortality , discharge on antithrombotics , and antihypertensive agents ) . Results — We included 1991 patients with ischemic stroke from 74 institutions in Argentina between November 2004 and October 2006 . Seventy-nine per cent of the patients were prescribed antithrombotic therapy within 48 hours of admission , but only 1 % received thrombolytics . No more than 5.7 % were admitted to stroke units . In-hospital pneumonia was diagnosed in 14.3 % of the patients and was higher in nonacademic facilities ( 16.4 % versus 11.4 % , P<0.02 ) . The overall adjusted in-hospital mortality was 9.1 % , also higher in nonacademic hospitals ( 10.6 % versus 7.1 % , P<0.008 ) . At discharge , antithrombotics were prescribed in 90.2 % and antihypertensive agents in 63.6 % of the patients . Conclusions — In ReNACer , there was a limited access to stroke units and thrombolytics , and a relatively high incidence of in-hospital pneumonia . Differences in stroke care were observed between academic and nonacademic institutions . There is an urgent need to develop national stroke programs in Argentina Cardiovascular disease remains the primary cause of mortality , and a major cause of disability in the developed world.1 This significant burden necessitates ongoing improvements in patient management , to minimize the impact of cardiovascular conditions on both patients and healthcare systems . These improvements in cardiovascular care are promoted by an evidence -based approach , shaped by comprehensive clinical guidelines . The scientific basis of recommendations is an important feature of clinical guidelines , and influences the degree to which they are followed in clinical practice .2 Recent studies have assigned the highest evidence grading to r and omized controlled trials ( RCTs ) that are clinical ly important , and representative of the clinical population covered by the guideline recommendation .3 For example , this highest grading was assigned to a recommendation based on a meta- analysis of RCTs showing low-dose diuretics to be the most effective first-line treatment for cardiovascular event prevention in hypertensive patients . This study review ed data from 42 RCTs which were , crucially , representative of the population that the recommendation was made for ( i.e. hypertensive patients ) .3,4 The importance of the applicability of evidence to recommendations highlights the need to consider evidence from clinical ly relevant situations , not all of which have been assessed by RCTs . This evidence can originate from expert consensus , as well as non-r and omized prospect i ve studies . Although generally providing a lower evidence -level than RCTs , 3,5 observational studies can make an important contribution to the evidence base when the study outcomes are clinical ly important , and the population s involved are representative . Indeed , information from several registries was considered in the recent American Heart Association Acute Coronary Care in the Elderly Scientific Statement.6 Non-r and omized prospect i ve registries document the treatment and outcomes for consecutive patients in clinical practice . Therefore , data are gained from a ‘ real-world ’ selection of patients , many of whom would be excluded from RCTs , OBJECTIVE To estimate the effect of multicentre surveillance for nosocomial infections on patients ' risk of surgical site infection ( SSI ) . DESIGN Prospect i ve multi-centre cohort study , from January 1996 to December 2000 . SETTING Acute care hospitals in The Netherl and s. STUDY PARTICIPANTS All 50 hospitals performing surveillance for one of seven selected procedures in the Dutch surveillance network for nosocomial infections PREZIES were invited . Thirty-seven hospitals participated ( 74 % ) and provided information on 21 920 operations , after which 885 ( 4 % ) SSI occurred . INTERVENTIONS The surveillance comprised the following : Development of surveillance methodology by multidisciplinary team ; use of a st and ardized registration protocol and software ; regular training of data collectors ; anonymous inter-hospital comparison of infection rates and feedback of results ; appointment of one contact person per hospital , responsible for data collection ; and dissemination of results to other health care professionals . Regular discussion of both successful and failing prevention strategies that had been instituted based on the surveillance results . OUTCOME MEASURE Risk of SSI . RESULTS The risk of infection was reduced for patients who had an operation during the fourth surveillance year ( RR = 0.69 ; 95 % confidence interval ( CI ) = 0.52 - 0.89 ) and decreased further for patients operated on during the fifth surveillance year ( RR = 0.43 ; CI = 0.24 - 0.76 ) as compared with patients who underwent surgery within one year of the start of surveillance in their hospital . No significant risk reduction was observed for patients operated on during the second and third surveillance years . CONCLUSION Surveillance , supported by participation in a surveillance network , reduced the risk of SSI in surgical patients registered in the Dutch surveillance network PREZIES . Our results suggest that infection control teams need to be perseverant and that surveillance programmes should be given time before evaluation Background — A treatment gap exists between heart failure ( HF ) guidelines and the clinical care of patients . The Registry to Improve the Use of Evidence -Based Heart Failure Therapies in the Outpatient Setting ( IMPROVE HF ) prospect ively tested a multidimensional practice -specific performance improvement intervention on the use of Output:	The measures of impact of registries were multifarious and included change in processes of care , quality of care , treatment outcomes , adherence to guidelines and survival . Despite the large number of published articles using data derived from CQRs , few have rigorously evaluated the impact of the registry as an intervention on improving health outcomes . Those that have evaluated this impact have mostly found a positive impact on healthcare processes and outcomes .
MS22191	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background A simple and accurate survival prediction tool can facilitate decision making processes for hospice patients with advanced cancers . The objectives of this study were to explore the association of cardiac autonomic functions and survival in patients with advanced cancer and to evaluate the prognostic value of heart rate variability ( HRV ) in 7-day survival prediction . Methods A prospect i ve study was conducted on 138 patients with advanced cancer recruited from the hospice ward of a regional hospital in southern Taiwan . Information on functional status and symptom burden of the patients was recorded . Frequency-domain HRV was obtained for the evaluation of cardiac autonomic functions at admission . The end point of the study was defined as the survival status at day 7 after admission to the hospice ward . Multivariate logistic regression analyses were performed to evaluate the independent associations between HRV indices and survival of 7 days or less . Results The median survival time of the patients was 20 days ( 95 % CI , 17–28 days ) . Results from the multivariate logistic regression analysis indicated that the natural logarithm-transformed high-frequency power ( lnHFP ) of a value less than 2 ( OR = 3.8 , p = 0.008 ) and ECOG performance status of 3 or 4 ( OR = 3.4 , p = 0.023 ) were significantly associated with a higher risk of survival of 7 days or less . Receiver operating characteristic ( ROC ) curve analysis revealed that the area under the curve was 0.71 ( 95 % CI , 0.61–0.81 ) . Conclusions In hospice patients with non-lung cancers , an lnHPF value below 2 at hospice admission was significantly associated with survival of 7 days or less . HRV might be used as a non-invasive and objective tool to facilitate medical decision making by improving the accuracy in survival prediction In patients with drug-resistant hypertension , chronic electric stimulation of the carotid baroreflex is an investigational therapy for blood pressure reduction . We hypothesized that changes in cardiac autonomic regulation can be demonstrated in response to chronic baroreceptor stimulation , and we analyzed the correlation with blood pressure changes . Twenty-one patients with drug-resistant hypertension were prospect ively included in a sub study of the Device Based Therapy in Hypertension Trial . Heart rate variability and heart rate turbulence were analyzed using 24-hour ECG . Recordings were obtained 1 month after device implantation with the stimulator off and after 3 months of chronic electric stimulation ( stimulator on ) . Chronic baroreceptor stimulation decreased office blood pressure from 185±31/109±24 mm Hg to 154±23/95±16 mm Hg ( P<0.0001/P=0.002 ) . Mean heart rate decreased from 81±11 to 76±10 beats per minute−1 ( P=0.001 ) . Heart rate variability frequency-domain parameters assessed using fast Fourier transformation ( FFT ; ratio of low frequency : high frequency : 2.78 versus 2.24 for off versus on ; P<0.001 ) were significantly changed during stimulation of the carotid baroreceptor , and heart rate turbulence onset was significantly decreased ( turbulence onset : −0.002 versus −0.015 for off versus on ; P=0.004 ) . In conclusion , chronic baroreceptor stimulation causes sustained changes in heart rate variability and heart rate turbulence that are consistent with inhibition of sympathetic activity and increase of parasympathetic activity in patients with drug-resistant systemic hypertension ; these changes correlate with blood pressure reduction . Whether the autonomic modulation has favorable cardiovascular effects beyond blood pressure control should be investigated in further studies BACKGROUND Patients with coronary heart disease ( CHD ) who experience depressed mood or psychological stress exhibit decreased vagal control of heart rate ( HR ) , as assessed by spectral analysis of HR variability ( HRV ) . Myocardial infa rct ion and sudden cardiac death are independently associated with depression and stress , as well as impaired vagal HR control . This study examined whether a behavioral neurocardiac intervention to reduce stress or depression can augment cardiovagal modulation in CHD patients . We hypothesized that ( 1 ) cognitive-behavioral training with HRV biofeedback would augment vagal recovery from acute stress , and ( 2 ) vagal regulation of HR would be inversely associated with stress and depression after treatment . METHODS This r and omized controlled trial enrolled 46 CHD patients from 3 clinics of CHD risk reduction in Toronto and Vancouver , Canada . Subjects were r and omized to five 1.5-hour sessions of HRV biofeedback or an active control condition . Outcome was assessed by absolute and normalized high-frequency spectral components ( 0.15 - 0.50 Hz ) of HRV , and by the Perceived Stress Scale and Centre for Epidemiologic Studies in Depression scale . RESULTS Both groups reduced symptoms on the Perceived Stress Scale ( P = .001 ) and Centre for Epidemiologic Studies in Depression scale ( P = .004 ) . Hierarchical linear regression determined that improved psychological adjustment was significantly associated with the high-frequency index of vagal HR modulation only in the HRV biofeedback group . Adjusted R 2 was as follows : HRV biofeedback group , 0.86 for stress ( P = .02 ) and 0.81 for depression ( P = .03 ) ; versus the active control group , 0.04 ( P = .57 ) and 0.13 ( P = .95 ) , respectively . CONCLUSION A novel behavioral neurocardiac intervention , HRV biofeedback , can augment vagal HR regulation while facilitating psychological adjustment to CHD Recent studies suggest that vagal nerve activity , indexed by heart rate variability ( HRV ) , could have a prognostic role in cancer . However , most studies did not control adequately for confounders and included cardiac patients . Furthermore , the validity of this prognostic role needs to be tested in different types of cancer . The present study tested the prognostic role of HRV in prostate cancer ( PC ) and non-small cell lung cancer ( NSCLC ) patients , using a historical prospect i ve design . HRV was derived from brief 10 sec ECGs obtained at approximately the time of diagnosis in 113 PC patients and 133 NSCLC patients . Outcomes included prostate-specific antigen ( PSA ) at 6 and 24 months in PC , and overall survival ( OS ) ( for the full sample ) and survival time ( for the deceased patients ) in NSCLC . Furthermore , the possible mediating role of C-reactive protein ( CRP ) was tested ( in NSCLC ) , as well as whether age and stage moderated the relationship between HRV and prognosis in both types of cancer . In the PC patients , HRV significantly inversely predicted PSA levels at 6 and 24 months , independent of confounders . Furthermore , this was particularly significant in metastatic PC patients , indicating moderation by stage . In NSCLC patients , HRV did not predict OS and survival time , but it did positively predict survival time in patients under the age of 65 , independent of confounders . Additionally , CRP was not found to mediate the relationship between HRV and OS or survival time in NSCLC . The present results partly support previous studies and extend them to two additional common types of cancer , using a more rigorous control over confounders . Together with recent experimental findings , these results propose a modulatory role of vagal nerve activity in cancer . Therefore , routine measurement of HRV in estimating prognosis in cancer may be considered In a historical prospect i ve cohort investigation of 4131 patients undergoing peptic ulcer surgery in 53 hospitals in the western part of Denmark from 1955 through 1960 , the risk of subsequent gastric cancer development was studied . The patients were followed with regard to gastric cancer development until their death or the end of the year 1982 and the incidence of cancer in this cohort was compared to the incidence in the total population in the same region during the same period . A total of 46 gastric cancers were diagnosed versus 47 expected . Up to 15 years after operation the cancer risk was lower than expected . After 15 years the risk was higher than expected with a 2.1-fold higher incidence after 25 years for the total patient population . The highest risk was observed in male subjects undergoing a Billroth II subtotal gastrectomy with a 3.2 times increase in risk after 25 years . There was no difference between gastric and duodenal ulcer patients ; and patients undergoing simple suture for a perforated ulcer showed no increase in cancer incidence . Patients with long-lasting symptoms had the same incidence as patients with briefer symptoms . These observations indicate that the operation per se and not the ulcer disease may be precancerous The present study was design ed to examine the effect of heart rate variability ( HRV ) biofeedback on the cardiorespiratory resting function during sleep in daily life . Forty-five healthy young adults were r and omly assigned to one of three groups : HRV biofeedback , Autogenic Training ( AT ) , and no-treatment control . Participants in the HRV biofeedback were instructed to use a h and held HRV biofeedback device before their habitual bedtime , those in the AT were asked to listen to an audiotaped instruction before bedtime , and those in the control were asked to engage in their habitual activity before bedtime . Pulse wave signal during sleep at their own residences was measured continuously with a wristwatch-type transdermal photoelectric sensor for three time points . Baseline data were collected on the first night of measurements , followed by two successive nights for HRV biofeedback , AT , or control . Cardiorespiratory resting function was assessed quantitatively as the amplitude of high-frequency ( HF ) component of pulse rate variability , a surrogate measure of respiratory sinus arrhythmia . HF component increased during sleep in the HRV biofeedback group , although it remained unchanged in the AT and control groups . These results suggest that HRV biofeedback before sleep may improve cardiorespiratory resting function during sleep OBJECTIVES The purpose of this study was to test the transcutaneous noninvasive vagus nerve stimulator ( nVNS ) ( gammaCore © ) device to determine if it modulates the peripheral immune system , as has been previously published for implanted vagus nerve stimulators . MATERIAL S AND METHODS A total of 20 healthy males and females were r and omized to receive either nVNS or sham stimulation ( SST ) . All subjects underwent an initial blood draw at 8:00 am , followed by stimulation with nVNS or SST at 8:30 am . Stimulation was repeated at 12:00 pm and 6:00 pm . Additional blood sample s were withdrawn 90 min and 24 hour after the first stimulation session . After sample s were cultured using the Myriad RBM TruCulture ( Austin , TX ) system ( WBCx ) , levels of cytokines and chemokines were measured by the Luminex assay and statistical analyses within and between groups were performed using the Wilcoxon Signed Ranks Test and Mann-Whitney U with the statistical program R. RESULTS A significant percent decrease in the levels of the cytokine interleukin [IL]-1β , tumor necrosis factor [ TNF ] levels , and chemokine , interleukin [IL]-8 IL-8 , macrophage inflammatory protein [MIP]-1α , and monocyte chemoattractant protein [MCP]-1 levels was observed in the nVNS group non-lipopolysaccharide (LPS)-stimulated whole blood culture ( n-WBCx ) at the 24-hour time point ( p < 0.05 ) . In SST group , there was a significant percent increase in IL-8 at 90 min post-stimulation ( p < 0.05 ) . At 90 min , the nVNS group had a greater percent decrease in IL-8 concentration ( p < 0.05 ) compared to SST group . The nVNS group had a greater percent decrease in cytokines ( TNF , IL-1β ) and chemokines ( MCP-1 and IL-8 ) at 24 hour ( p < 0.05 ) in comparison to SST . LPS-stimulated whole blood cultures ( L-WBCx ) did not show a significant decrease in cytokine levels in either the nVNS or SST group across any time points . The nVNS group showed a significant percent increase in LPS-stimulated IL-10 levels at the 24-hour time point in comparison to SST . CONCLUSIONS nVNS downregulates inflammatory cytokine release suggesting that nVNS may be an effective anti-inflammatory treatment Invasive vagus nerve stimulation has been demonstrated to be an effective treatment in major depressive episodes . Recently , a novel non-invasive method of stimulating the vagus nerve on the outer canal of the ear has been proposed . In healthy subjects , a prominent fMRI BOLD signal deactivation in the limbic system was found . The present pilot study investigates the effects of this novel technique of auricular transcutaneous electric nerve stimulation in depressed patients for the first time . A total of 37 patients suffering from major depression were included in two r and omized sham controlled add-on studies . Patients were stimulated five times a week on a daily basis for the duration of 2 weeks . On days 0 and 14 , the Hamilton Depression Rating Scale ( HAMD ) and the Beck Depression Inventory ( BDI ) were assessed . In contrast to sham-treated patients , electrically stimulated persons showed a significantly better outcome in the BDI . Mean decrease in the active treatment group was 12.6 ( SD 6.0 ) points compared to 4.4 ( SD 9.9 ) points in the sham group . HAMD score did not change significantly in the two groups . An antidepressant effect of a new transcutaneous auricular nerve stimulation technique has been shown Output:	These studies show that initially high vagal nerve activity predicts better cancer prognosis , and , in some studies , independent of confounders such as cancer stage and treatments . The second part of this paper presents a comprehensive review including human and animal cohort and experimental studies showing that vagotomy accelerates tumor growth , while vagal nerve activation improves cancer prognosis . Based on all review ed studies , it is concluded that the evidence supports a protective role of the vagus nerve in cancer and specifically in the metastatic stage
MS22192	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background A simple diabetes risk tool that does not require laboratory tests would be beneficial in screening individuals at higher risk . Few studies have evaluated the ability of these tools to identify new cases of pre-diabetes . This study aim ed to assess the ability of the American Diabetes Association Risk Tool ( ADART ) to predict the 3-year incidence of pre-diabetes and diabetes in Taiwanese . Methods This was a 3-year prospect i ve study of 1021 residents with normoglycemia at baseline , gathered from a r and om sample of residents aged 40–88 years in a metropolitan city in Taiwan . The areas under the curve ( AUCs ) of three models were compared : ADART only , ADART plus lifestyle behaviors at baseline , and ADART plus lifestyle behaviors and biomarkers at baseline . The performance of ADART was compared with that of 16 tools that had been reported in the literature . Results The AUCs and their 95 % confidence intervals ( CIs ) were 0.60 ( 0.54–0.66 ) for men and 0.72 ( 0.66–0.77 ) for women in model 1 ; 0.62 ( 0.56–0.68 ) for men and 0.74 ( 0.68–0.80 ) for women in model 2 ; and 0.64 ( 0.58–0.71 ) for men and 0.75 ( 0.69–0.80 ) for women in model 3 . The AUCs of these three models were all above 0.7 in women , but not in men . No significant difference in either women or men ( p = 0.268 and 0.156 , respectively ) was observed in the AUC of these three models . Compared to 16 tools published in the literature , ADART had the second largest AUC in both men and women . Conclusions ADART is a good screening tool for predicting the three-year incidence of pre-diabetes and diabetes in females of a Taiwanese population . The performance of ADART in men was similar to the results with other tools published in the literature . Its performance was one of the best among the tools reported in the literature BACKGROUND The aim of this study was to develop a risk score to predict the 4-year risk of diabetes in a middle-aged Korean cohort . METHODS AND RESULTS Participants without diabetes ( 6,342 participants , aged 40 - 69 years ) were included and biennial follow ups were conducted . A logistic regression analysis was used to construct the models . The basic model was based on simple information such as age , parental or sibling history of diabetes , smoking status , body mass index , and hypertension , while clinical model 1 was constructed by adding biochemical tests such as fasting plasma glucose , high-density lipoprotein-cholesterol and triglycerides to the basic model ; clinical model 2 further added glycated hemoglobin ( HbA(1c ) ) to clinical model 1 . The model accuracy was assessed using area under a receiver operating characteristic ( AROC ) curve and the Hosmer-Lemeshow statistics . Both net reclassification improvement ( NRI ) and integrated discrimination improvement ( IDI ) were calculated to determine the contribution of HbA(1c ) . Two clinical models improved model discrimination ( AROC=0.75 and 0.77 ) when compared with the basic model ( AROC=0.65 ) . The addition of HbA(1c ) to clinical model 1 increased AROC by only 0.02 despite its high impact on the prediction of diabetes ( odds ratio=2.66 ) . However , the NRI and IDI were significantly improved with the addition of HbA(1c ) Therefore , a risk score system was developed to estimate the 4-year risk of diabetes based on clinical model 2 . CONCLUSIONS A risk score derived from simple biochemical examinations including HbA(1c ) can help identify those at a high risk of diabetes in a middle-aged Korean cohort OBJECTIVE To create a simple prediction rule that could perform as well as the 2-h postchallenge plasma glucose ( PCPG ) test to predict those at risk for diabetes . We created a prediction rule in one sample and prospect ively vali date d it for incident diabetes in a separate cohort . RESEARCH DESIGN AND METHODS A cross-sectional analysis with data from the Rancho Bernardo Study ( age 67 + /- 11 years ) to derive a rule predicting abnormal PCPG > /=140 mg/dl , using demographic , clinical , and laboratory data of nondiabetic participants with fasting plasma glucose ( FPG ) < 126 mg/dl . Data from the Health , Aging and Body Composition study ( age 74 + /- 3 years ) were used to prospect ively vali date this rule for incident diabetes and compare it with the predictive ability of the PCPG test . RESULTS Of 1,549 RBS participants , 514 ( 33 % ) had PCPG > /=140 mg/dl . Female sex , age , triglycerides , and FPG were most significantly associated with abnormal PCPG . Based on st and ardized beta-coefficients , we allotted 1 point for female sex , triglycerides > /=150 mg/dl , or FPG 95 - 104 mg/dl . Age > /=70 years or FPG 105 - 115 mg/dl were given 2 points , and FPG 116 - 125 mg/dl received 3 points . In the validation cohort , this simple prediction rule was as good as the 2-h PCPG test for predicting incident diabetes ( C-statistic : 0.71 for both ) . CONCLUSIONS Advanced age , female sex , FPG , and triglycerides were able to predict adults at risk for diabetes equally well as the 2-h PCPG test . Using this rule , clinicians may better identify older persons who should receive intensive lifestyle intervention to prevent type 2 diabetes OBJECTIVE Hemoglobin A1c ( HbA1c ) can be used to assess type 2 diabetes ( T2D ) risk . We asked whether HbA1c was associated with T2D risk in four scenarios of clinical information availability : 1 ) HbA1c alone , 2 ) fasting laboratory tests , 3 ) clinic data , and 4 ) fasting laboratory tests and clinic data . RESEARCH DESIGN AND METHODS We studied a prospect i ve cohort of white ( N = 11,244 ) and black ( N = 2,294 ) middle-aged participants without diabetes in the Framingham Heart Study and Atherosclerosis Risk in Communities study . Association of HbA1c with incident T2D ( defined by medication use or fasting glucose [ FG ] ≥126 mg/dL ) was evaluated in regression models adjusted for 1 ) age and sex ( demographics ) ; 2 ) demographics , FG , HDL , and triglycerides ; 3 ) demographics , BMI , blood pressure , and T2D family history ; or 4 ) all preceding covariates . We combined results from cohort and race analyses by r and om-effects meta-analyses . Subsidiary analyses tested the association of HbA1c with developing T2D within 8 years or only after 8 years . RESULTS Over 20 years , 3,315 individuals developed T2D . With adjustment for demographics , the odds of T2D increased fourfold for each percentage-unit increase in HbA1c . The odds ratio ( OR ) was 4.00 ( 95 % CI 3.14 , 5.10 ) for blacks and 4.73 ( 3.10 , 7.21 ) for whites , result ing in a combined OR of 4.50 ( 3.35 , 6.03 ) . After adjustment for fasting laboratory tests and clinic data , the combined OR was 2.68 ( 2.15 , 3.34 ) over 20 years , 5.79 ( 2.51 , 13.36 ) within 8 years , and 2.23 ( 1.94 , 2.57 ) after 8 years . CONCLUSIONS HbA1c predicts T2D in different common scenarios and is useful for identifying individuals with elevated T2D risk in both the short- and long-term OBJECTIVE To evaluate the incidence and relative risk of type 2 diabetes defined by the newly proposed HbA1c diagnostic criteria in groups categorized by different baseline HbA1c levels . RESEARCH DESIGN AND METHODS Using data from the European Prospect i ve Investigation of Cancer (EPIC)-Norfolk cohort with repeat HbA1c measurements , we estimated the prevalence of known and previously undiagnosed diabetes at baseline ( baseline HbA1c ≥6.5 % ) and the incidence of diabetes over 3 years . We also examined the incidence and corresponding odds ratios ( ORs ) by different levels of baseline HbA1c . Incident diabetes was defined clinical ly ( self-report at follow-up , prescribed diabetes medication , or inclusion on a diabetes register ) or biochemically ( HbA1c ≥6.5 % at the second health assessment ) , or both . RESULTS The overall prevalence of diabetes was 4.7 % ; 41 % of prevalent cases were previously undiagnosed . Among 5,735 participants without diabetes at baseline ( identified clinical ly or using HbA1c criteria , or both ) , 72 developed diabetes over 3 years ( 1.3 % [ 95 % CI 1.0–1.5 ] ) , of which 49 % were identified using the HbA1c criteria . In 6 % of the total population , the baseline HbA1c was 6.0–6.4 % ; 36 % of incident cases arose in this group . The incidence of diabetes in this group was 15 times higher than in those with a baseline HbA1c of < 5.0 % ( OR 15.5 [ 95 % CI 7.2–33.3 ] ) . CONCLUSIONS The cumulative incidence of diabetes defined using a newly proposed HbA1c threshold in this middle-aged British cohort was 1.3 % over 3 years . Targeting interventions to individuals with an HbA1c of 6.0–6.4 % might represent a feasible preventive strategy , although complementary population -based preventive strategies are also needed to reduce the growing burden of diabetes Aims In a population at risk for type 2 diabetes ( T2DM ) , we assessed early physical and metabolic markers that predict progression from normal to impaired glucose tolerance ( IGT ) and T2DM . Methods A total of 388 individuals ( 22 % male , age 46 + 11 years ) at risk for T2DM were r and omized to St and ard ( n = 182 ) or Intervention ( n = 206 ) care and evaluated at baseline and 5 annual follow-up visits , including blood pressure , BMI , A1C , lipids , urine albumin/creatinine ratio , VO2max , fasting glucose , insulin and C-peptide . The St and ard group received results of annual lab tests and quarterly newsletters , while the Intervention group received quarterly newsletters and detailed discussion s of lab results , routine self-directed activities , semi-annual group meetings and monthly telephone calls for ongoing support . Results Overall , 359 ( 93 % ) returned for at least one follow-up visit and 272 ( 70 % ) completed the final 5-year assessment . Return rates , changes in measures and incidence of IGT/T2DM were similar between groups . Low cardiorespiratory fitness ( VO2max ) was the most prevalent baseline abnormality . A1C and BMI were significant predictors of IGT/T2DM after controlling for other factors . The risk of IGT/T2DM within 5 years was 17.16 ( 95 % CL : 6.169 , 47.736 ) times greater for those with baseline A1C>=5.8 % as compared to those < 5.8 % ( p < 0.0001 ) . Conclusion Baseline A1C>=5.8 % was a significant predictor of IGT/T2DM within 5 years in a population at high risk for T2DM . A1C is routinely performed among patients with diabetes , however these data and other evidence suggest that it may also be a useful tool for risk assessment and screening OBJECTIVE Although an excess transmission of type 2 diabetes from mothers has been documented , whether this is an independent trait or whether the effect can be detected early through risk factors for type 2 diabetes remains to be eluci date d. The objective of this study was to investigate the prevalence of and the possible prospect i ve effect of family history on type 2 diabetes incidence adjusted for multiple diabetes risk factors in a 22.5-year follow-up study of healthy men . RESEARCH DESIGN AND METHODS A total of 1,947 apparently healthy nondiabetic men with fasting blood glucose ( FBG ) levels < 110 mg/dl at baseline , in whom an intravenous glucose tolerance test ( IVGTT ) was administered and several conventional risk factors were measured , were followed for 22.5 years . Family history data were obtained at the baseline examination , and morbidity data were obtained from repeated investigations , hospital records , and death certificates . RESULTS A total of 131 men reported maternal diabetes family history only , 65 men reported paternal diabetes family history only and 10 men reported both maternal and paternal diabetes family history . Among the 1,947 men , 143 cases of type 2 diabetes developed during 22.5 years of observation . Output:	Taking into account the long-term follow-up of cohort studies , estimation of HRs for time-dependent events like T2DM incidence appeared most reliable . Overall prognosis of people with IH worsened over time . T2DM cumulative incidence generally increased over the course of follow-up but varied with IH definition . Regression from IH to normoglycaemia decreased over time but was observed even after 11 years of follow-up . The risk of developing T2DM when comparing IH with normoglycaemia at baseline varied by IH definition .
MS22193	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Postnatal depression affects 10–15 % of all mothers in Western societies and remains a major public health concern for women from diverse cultures . British Pakistani and Indian women have a higher prevalence of depression in comparison to their white counterparts . Research has shown that culturally adapted interventions using Cognitive Behavioural Therapy ( CBT ) may be acceptable and may help to address the needs of this population . The aim of this study was to assess the acceptability and overall experience of the Positive Health Programme by British South Asian mothers . Methods This was a nested qualitative study , part of an exploratory r and omized controlled trial ( RCT ) conducted to test the feasibility and acceptability of a culturally-adapted intervention ( Positive Health Programme or PHP ) for postnatal depression in British South Asian women . In-depth interviews ( N = 17 ) were conducted to determine the views of the participants on the feasibility and acceptability of the intervention . Results The participants found the intervention acceptable and experienced an overall positive change in their attitudes , behaviour , and increased self-confidence . Conclusions The findings suggest that the culturally adapted Positive Health Programme is acceptable to British South Asian women . These results support that culturally sensitive interventions may lead to better health outcomes and overall satisfaction . Trial registration Protocol registered on Clinical trials.gov Background In the UK , 8–15 % of women suffer from postnatal depression with long term consequences for maternal mood and child development . Current guidelines state that health visitors and GPs should continue to have a major role in the detection and management of postnatal depression . Previous literature suggests that women are reluctant to disclose symptoms of postnatal depression . This study aim ed to explore general practitioners ' ( GPs ) , health visitors ' and women 's views on the disclosure of symptoms which may indicate postnatal depression in primary care . Methods In-depth interviews with GPs , health visitors and women who were participating in a r and omised controlled trial of anti-depressants versus health visitor delivered non-directive counselling for the treatment of postnatal depression . Interviews were audio-taped and fully transcribed . Thematic analysis with an iterative approach was used , allowing the views of practitioners and patients to be explored and then compared . Results Nineteen GPs , 14 health visitors and 28 women were interviewed . A number of common themes were identified across all three data sets : underst and ing and negotiating the diagnosis of postnatal depression , hindering and facilitating disclosure , and the system of care . Both women and health professionals described postnatal depression in psychosocial terms : an adjustment reaction to change in life circumstances and the reality of motherhood not meeting personal expectations . Women described making a conscious decision about whether or not to disclose their feelings to their GP or health visitor . Health professionals described strategies used to hinder disclosure and described a reluctance to make a diagnosis of postnatal depression , as they had few personal re sources to manage women with postnatal depression themselves , and no services to which to refer women for further treatment . Conclusion To improve disclosure of symptoms in primary care , there should be a move away from question ing why health professionals do not make the diagnosis of depression and in response suggesting that education and training will improve skills and thus improve detection of depression . Improving the detection and management of postnatal depression in primary care requires recognition of the context in which women consult , and system changes that ensure health professionals work in an environment that can facilitate disclosure and that the necessary re sources for management are available . Trail Registration IS RCT N BACKGROUND In the UK , 8 - 15 % of women suffer from postnatal depression , with long-term consequences for maternal mood and child development . Previous literature suggests that health visitors struggle with their conflicting roles with respect to mother and infant . Current policy is redirecting the emphasis and organisation of health visitor work , but guidelines state that health visitors and GPs should continue to have a major role in the detection and management of postnatal depression . AIM To explore the views of GPs and health visitors on the diagnosis and management of postnatal depression . DESIGN OF STUDY A qualitative study nested within a multicentre r and omised controlled trial . SETTING Nine primary care trusts in Bristol , Manchester , and London . METHOD In-depth interviews with GPs and health visitors from primary care trusts participating in a r and omised controlled trial of antidepressants versus health visitor-delivered non-directive counselling . Interviews were audiotaped and fully transcribed . Thematic analysis with an iterative approach was used to develop conceptual categories from the transcripts . RESULTS Nineteen GPs and 14 health visitors were interviewed . GPs and health visitors described their work in making and negotiating the diagnosis of postnatal depression , the value of a long-term relationship with the woman , and how labelling affects management of women with postnatal depression . Responders described how they viewed others ' roles in the management of postnatal depression , and how national policy and local organisational changes had an impact on patient care , so that no one health professional was assuming overall responsibility for the care of women with postnatal depression . CONCLUSION Ongoing organisational changes within primary care , such as the implementation of corporate working by health visitors , affect care provided to women after birth , which in turn has an impact on the diagnosis and management of postnatal depression BACKGROUND Postnatal depression is a public health problem requiring intervention . To provide effective care , information is needed on the experiences of those with high levels of depressive symptoms who are offered and accept , or decline , psychological intervention postnatally . AIM To provide the first integrated in-depth exploration of postnatal women 's experiences of the identification and management of symptoms of depression and the offer and acceptance of postnatal care by health visitors taking part in the PoNDER trial . SETTING General practice : primary care within the former Trent regional health authority , Engl and . METHOD Thirty women with 6-week Edinburgh Postnatal Depression Scale ( EPDS ) scores ≥ 18 and probable depression completed semi-structured interviews . All women had taken part in the Post-Natal Depression Economic Evaluation and R and omised controlled ( PoNDER ) trial where intervention group health visitors received training in identification of depressive symptoms and provided psychologically informed sessions based on cognitive-behavioural therapy or person-centred counselling principles . RESULTS When accepted , psychological sessions were experienced as positive , effective , and ' ideal care ' . Women approved of using the EPDS but did not underst and the health visitor 's role in supporting women . Seeking help and accepting sessions depended on women 's perspectives of their health visitor as an individual . CONCLUSION Women 's experience of their health visitors providing psychological sessions to help with postnatal depressive symptoms is highly positive . Women will better accept support from health visitors if they recognise their role in postnatal depression and find them easy to relate to on personal matters . There is a case for specific enhancement of interpersonal skills in health visiting , or alternatively offering a choice of health visitors to women Output:	Conclusions Complex , interlinking , multilevel barriers to accessing mental health services for women with perinatal mental illness exist .
MS22194	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The aim of this study was to compare the performance of the Paediatric Canadian Triage and Acuity Scale ( Paed CTAS ) to a previous triage tool with respect to the percentage of admissions , the diagnostic and therapeutic interventions , and the mean pediatric risk of admission ( PRISA ) score in a pediatric tertiary center emergency department . Data were prospect ively collected for 4 months before the Paed CTAS introduction ( PRE group ) and for 4 months after its implementation ( Paed CTAS group ) . Both groups were similar in chief complaints , distribution of triage levels , and mean PRISA score . In the Paed CTAS group , more patients were triaged in the higher acuity levels ( 53 % vs 36 % , P < .05 ) , but the percentage of admission for these patients was comparatively lower ( 13 % vs 27 % , P<.05 ) . The ability to predict admission was greater for the PRE tool as compared to the Paed CTAS tool ( AUC : 0.82 vs 0.69 , P=.001 ) . The ability to predict requirements for interventions such as blood culture and intravenous fluid bolus was similar for both triage tools OBJECTIVES The objective was to compare the validity of an existing informally structured triage system with the Emergency Severity Index ( ESI ) and the Manchester Triage System ( MTS ) . METHODS A total of 900 patients were prospect ively triaged by six trained triage nurses using the three systems . Triage ratings of 421 ( 48 % ) patients treated only by emergency department ( ED ) physicians were compared with a reference st and ard determined by an expert panel . The percentage of undertriage , the sensitivity , and the specificity for each urgency level were calculated . The relationship between urgency level , re source use , hospitalization , and length of stay ( LOS ) in the 900 triaged patients was determined . RESULTS The percentage of undertriage using the ESI ( 86 of 421 ; 20 % ) was significantly higher than in the MTS ( 48 of 421 ; 11 % ) . When combining urgency levels 4 and 5 , the percentage of undertriage was 8 % for the informally structured system ( ISS ) , 14 % for the ESI , and 11 % for the MTS . In all three systems , sensitivity for all urgency levels was low , but specificity for levels 1 and 2 was high ( > 92 % ) . Sensitivity and specificity were significantly different between ESI and MTS only in urgency level 4 . In all 900 patients triaged , urgency levels across all systems were associated with significantly increased re source use , hospitalization rate , and LOS . CONCLUSIONS All three triage systems appear to be equally valid . Although the ESI showed the highest percentage of undertriage and the ISS the lowest , it seems preferable to use a verifiable , formally structured triage system BACKGROUND / PURPOSE Since the implementation of National Health Insurance in Taiwan , Emergency Department ( ED ) volume has progressively increased , and the current triage system is insufficient and needs modification . This study compared the prioritization and re source utilization differences between the four-level Taiwan Triage System ( TTS ) and the st and ardized five-level Canadian Triage and Acuity Scale ( CTAS ) among ED patients . METHODS This was a prospect i ve observational study . All adult ED patients who presented to three different medical centers during the study period were included . Patients were independently triaged by the duty triage nurse using TTS , and a single trained research nurse using CTAS with a computer support software system . Hospitalization , length of stay ( LOS ) , and medical re source consumption were analyzed by comparing TTS and CTAS by acuity levels . RESULTS There was significant disparity in patient prioritization between TTS and CTAS among the 1851 enrolled patients . With TTS , 7.8 % , 46.1 % , 45.9 % and 0.2 % were assigned to levels 1 , 2 , 3 , and 4 , respectively . With CTAS , 3.5 % , 24.4 % , 44.3 % , 22.4 % and 5.5 % were assigned to levels 1 , 2 , 3 , 4 , and 5 , respectively . The hospitalization rate , LOS , and medical re source consumption differed significantly between the two triage systems and correlated better with CTAS . CONCLUSION CTAS provided better discrimination for ED patient triage , and also showed greater validity when predicting hospitalization , LOS , and medical re source consumption . An accurate five-level triage scale appeared superior in predicting patient acuity and re source utilization INTRODUCTION The study objectives were to compare reliability and validity of a 3-level ( 3L ) triage system with a new 5-level ( 5L ) triage system and determine the effect of nursing experience on triage reliability . METHODS The study was conducted in a southeastern tertiary emergency department . With a stratified r and om sample , reliability of 3L triage ratings was measured with weighted kappa ( time 1 ) . The 5L system was then implemented , and weighted kappa was remeasured ( time 2 ) . Validity was assessed by comparing case mix , sensitivity , and specificity at times 1 and 2 , and comparing 5L ratings with physician billing ( Evaluation and Management ) codes and nursing re source intensity at time 2 . RESULTS Time 1 case mix ( 15,324 patients ) was : level 1 , 6 % ; level 2 , 36 % ; level 3 , 59 % , and time 2 ( 16,024 patients ) was : level 1 , 1 % ; level 2 , 8 % ; level 3 , 38 % ; level 4 , 41 % ; level 5 , 13 % . Three hundred-five triage ratings were evaluated from time 1 , and 303 were evaluated from time 2 . Weighted kappa was 0.53 for time 1 and 0.68 for time 2 . Spearman correlations were : 5L and nursing re source intensity , 0.55 ( P < .0001 ) ; and 5L and Em , 0.57 ( P < .0001 ) . Sensitivity was 58 % for the 3L and 68 % for the 5L . Specificity was 83 % for the 3L and 91 % for the 5L . Under-triage rates were 28 % for the 3L and 12 % for the 5L , and less-experienced nurses were more likely to under-triage using the 3L system . DISCUSSION The 5L triage system is safer and provides greater discrimination , better reliability , and improved sensitivity and specificity than the 3L triage system Objective An ideal emergency department ( ED ) triage system accurately prioritises patients on the basis of the urgency of interventions required to avoid under- or over-triage . The objective of this study was to develop and vali date a five-level Taiwan triage and acuity scale ( TTAS ) with an electronic decision support tool . Methods This prospect i ve , multicentre , observational study included 10533 patients triaged at 11 academic medical centres , 18 regional and four district hospitals . Adult patients presenting to the ED were independently triaged by the duty triage nurse in the usual way and trained research nurses using TTAS with a computerised decision support system . Weighted κ statistics were used to assess the reproducibility . Hospitalisation , length of stay , and medical re source consumption were analysed by TTAS acuity levels . Results Most cases were stratified into levels 2 to 3 by the existing four-level triage system , whereas the TTAS stratified most patients to levels 3 ( 41.4 % ) and 4 ( 25.0 % ) , and only a small number to level 1 ( 3.9 % ) ( resuscitation ; most urgent ) . Weighted κ for TTAS assignment was 0.87 ( 95 % CI 0.85 to 0.89 ) . The decrease in mean medical re source consumption and hospitalisation rate was statistically significant with each decrease in the TTAS triage acuity level . The length of stay also decreased significantly as the TTAS level acuity fell from levels 2 to 5 . Conclusions The TTAS was found to be a reliable triage system that accurately prioritises the treatment needed to avoid overtriage , more efficiently deploying the appropriate re sources to ED patients INTRODUCTION Each of the two most commonly used five-level triage tools in North America , the Emergency Severity Index and the Canadian Triage and Acuity Scale have been used as a measure of emergency department re source utilization in addition to acuity . In both cases , it is believed that patients triaged as having a higher level of acuity require a greater number of emergency department re sources . We compared the ability of each tool to predict the emergency department re sources for each emergency department visit and associated hospital admission and in-hospital mortality rates . METHODS This is an observational , cohort study of a population -based r and om sample of patients triaged at two emergency departments over a 4-month period . Correlational analyses were performed to examine the relationship between the triage assessment and : ( i ) re source utilization , ( ii ) hospital admission , and ( iii ) in-hospital mortality . RESULTS From 486 patients , analyses revealed the greatest correlation was between Emergency Severity Index and diagnostic re sources [ -0.54 ( 95 % confidence intervals : -0.58 , -0.50 ) ] and the poorest correlation was between Canadian Triage and Acuity Scale and mortality [ -0.16 ( 95 % confidence intervals : -0.20 , -0.12 ) ] . No statistically significant differences ( P<0.005 ) were observed between each tool 's ability to predict any of the outcomes measured . CONCLUSION No statistically significant difference was observed in the ability of Emergency Severity Index v. 3 and Canadian Triage and Acuity Scale to predict emergency department re source utilization or immediate patient outcomes . This ability is , at best , only moderate indicating that other , more accurate tools than measures of triage acuity are required for this purpose BACKGROUND Triage system in children seems to be more challenging compared to adults because of their different response to physiological and psychosocial stressors . This study aim ed to determine the best triage system in the pediatric emergency department . METHODS This was a prospect i ve observational study . This study was divided into two phases . The first phase determined the inter-rater reliability of five triage systems : Manchester Triage System ( MTS ) , Emergency Severity Index ( ESI ) version 4 , Pediatric Canadian Triage and Acuity Scale ( CTAS ) , Australasian Triage Scale ( ATS ) , and Ramathibodi Triage System ( RTS ) by triage nurses and pediatric residents . In the second phase , to analyze the validity of each triage system , patients were categorized as two groups , i.e. , high acuity patients ( triage level 1 , 2 ) and low acuity patients ( triage level 3 , 4 , and 5 ) . Then we compared the triage acuity with actual admission . RESULTS In phase I , RTS illustrated almost perfect inter-rater reliability with kappa of 1.0 ( P<0.01 ) . ESI and CTAS illustrated good inter-rater reliability with kappa of 0.8 - 0.9 ( P<0.01 ) . Meanwhile , ATS and MTS illustrated moderate to good inter-rater reliability with kappa of 0.5 - 0.7 ( P<0.01 ) . In phase II , we included 1 041 participants with average age of 4.7±4.2 years , of which 55 % were male and 45 % were female . In addition 32 % of the participants had underlying diseases , and 123 ( 11.8 % ) patients were admitted . We found that ESI illustrated the most appropriate predicting ability for admission with sensitivity of 52 % , specificity of 81 % , and AUC 0.78 ( 95%CI 0.74 - 0.81 ) . CONCLUSION RTS illustrated almost perfect inter-rater reliability . Meanwhile , ESI and CTAS illustrated good inter-rater reliability . Finally , ESI illustrated the appropriate validity for triage system Objective To measure and compare the reliability and predictive validity of a four-level triage system ( I-4L ) and the new four-level model triage emergency method ( TEM ) . Methods This observational study was conducted in an urban hospital . Ten nurses were r and omly selected to assign a triage level to 189 paper scenarios , using either the I-4L model ( 5 nurses ) or the TEM model ( 5 nurses ) . We used weighted κ statistics to measure the interrater and intrarater reliability of each triage tool and assessed the validity of each models based on the accuracy in predicting admission . Results Interrater reliability was κ=0.73 [ 95 % CI ( confidence interval ) : 0.59–0.87 ] and κ=0.79 ( 95 % CI : 0.65–0.93 ) with I-4L and TEM , respectively . Intrarater reliability was κ=0.82 ( 95 % CI : 0.67–0.96 ) and κ=0.78 ( 95 % CI : 0.62–0.93 ) , respectively . The accuracy of triage rating for admission prediction was similarly good with I-4L and TEM , namely , 79 % ( 95 % CI : 74–85 ) and 77 % ( 95 % CI : 74–85 ) . The proportion of patients admitted per triage level was similar with the two models . Conclusion The interrater and intrarater reliability for rating triage acuity and for accuracy in patient admission prediction was good with both models . Performance with the new model was similar to that of I-4L despite the nurses ' short experience . The new TEM model has the advantage of Output:	Overall , validity of each triage system to identify high and low-urgency patients was moderate to good , but performance was highly variable . In a subgroup analysis , no clear association was found between ED patient volume or casemix severity of illness and triage systems ' performance . Established triage systems show a reasonable validity for the triage of patients at the ED , but performance varies considerably .
MS22195	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objective This study aims to determine the efficacy of yoga in alleviating vasomotor symptoms ( VMS ) frequency and bother . Methods This study was a three-by-two factorial , r and omized controlled trial . Eligible women were r and omized to yoga ( n = 107 ) , exercise ( n = 106 ) , or usual activity ( n = 142 ) , and were simultaneously r and omized to a double-blind comparison of & ohgr;-3 fatty acid ( n = 177 ) or placebo ( n = 178 ) capsules . Yoga intervention consisted of 12 weekly 90-minute yoga classes with daily home practice . Primary outcomes were VMS frequency and bother assessed by daily diaries at baseline , 6 weeks , and 12 weeks . Secondary outcomes included insomnia symptoms ( Insomnia Severity Index ) at baseline and 12 weeks . Results Among 249 r and omized women , 237 ( 95 % ) completed 12-week assessment s. The mean baseline VMS frequency was 7.4 per day ( 95 % CI , 6.6 to 8.1 ) in the yoga group and 8.0 per day ( 95 % CI , 7.3 to 8.7 ) in the usual activity group . Intent-to-treat analyses included all participants with response data ( n = 237 ) . There was no difference between intervention groups in the change in VMS frequency from baseline to 6 and 12 weeks ( mean difference [ yoga − usual activity ] from baseline at 6 wk , −0.3 [ 95 % CI , −1.1 to 0.5 ] ; mean difference [ yoga − usual activity ] from baseline at 12 wk , −0.3 [ 95 % CI , −1.2 to 0.6 ] ; P = 0.119 across both time points ) . Results were similar for VMS bother . At week 12 , yoga was associated with an improvement in insomnia symptoms ( mean difference [ yoga − usual activity ] in the change in Insomnia Severity Index , 1.3 [ 95 % CI , −2.5 to −0.1 ] ; P = 0.007 ) . Conclusions Among healthy women , 12 weeks of yoga class plus home practice , compared with usual activity , do not improve VMS frequency or bother but reduce insomnia symptoms Objectives This study aim ed to investigate the effect of Educational program on quality of life ( QOL ) in menopausal women in 2016 in Hamadan , Iran . Methods In this clinical trial study , 100 postmenopausal women were r and omly selected and allocated to case and control group ( 50 per group ) . Data collection tool included question naires of demographic information and Menopause QOL , which were completed by the sample s before the intervention . In the case group , education program was run during 5 sessions for 45 to 60 minutes . Immediately and Three months after intervention , information were collected using question naire in both groups and they were analyzed using SPSS 16 software . Results The menopause women in both intervention and control groups had similar demographics . There was not a significant difference in the QOL mean scores in before of the intervention between the two groups of intervention and control in all dimension of QOL . There was a significantly difference in the mean of QOL scores between the two groups in immediately after the intervention and 3 months after the intervention in dimension of vasomotor , psychosocial , sexual and physical ( P < 0.001 ) . Conclusions This study recommend that a unit in health and treatment centers be established for training menopausal women about health care by holding didactic classes Menopausal Hormone Therapy ( MHT ) use in Australia fell by 55 % from 2001 to 2005 , following the release of large-scale findings on its risks and benefits . Comprehensive national data , including information on overall prevalence of MHT use as well as information on duration of use in Australia have not been reported since the 2004–5 National Health Survey , when 11 % of women aged 45 + years were estimated to be current MHT users . No national data are available on prevalence of use of “ bioidentical ” hormone therapy ( BHT ) . The objective of this study was to determine recent prevalence of MHT and BHT use . A cross-sectional , national , age-stratified , population survey was conducted in 2013 . Eligible women , aged 50–69 years , resident in Australia were r and omly sample d in 5-year age groups from the Medicare enrolment data base ( Australia ’s universal health scheme ) . The response rate was 22 % based on return of completed question naires , and analyses were restricted to 4,389 women within the specified age range . The estimated population -weighted prevalence of current use of MHT was 13 % ( 95%CI 12–14 ) , which was broadly similar to the previously reported national figures in 2004–5 , suggesting that the use of MHT in Australia has largely stabilised over the past decade . A total of 39 % and 20 % of current-users with an intact uterus reported use of oestrogen-progestagen MHT and oestrogen-only MHT , respectively , whereas 77 % of hysterectomised current-users used oestrogen-only MHT . Almost three-quarters of current-users [ population -weighted prevalence 9 % ( 95%CI 8–10 ) ] had used MHT for ≥5 years . In regard to BHT , estimated population -weighted prevalence of ever use was 6 % ( 95%CI 6–7 ) and 2 % ( 95%CI 2–3 ) for current use . The population -weighted prevalence of MHT and BHT combined , in current users in their fifties and sixties was 15 % ( 95%CI 14–16 ) . These data provide a recent national “ snapshot ” of Australian women ’s use of both conventional MHT and of BHT Clinical trials , systematic review s and guidelines compare beneficial and non-beneficial outcomes following interventions . Often , however , various studies on a particular topic do not address the same outcomes , making it difficult to draw clinical ly useful conclusions when a group of studies is looked at as a whole.1 This problem was recently thrown into sharp focus by a systematic review of interventions for preterm birth prevention , which found that among 103 r and omised trials , no fewer than 72 different outcomes were reported.2 There is a growing recognition among clinical research ers that this variability undermines consistent synthesis of the evidence , and that what is needed is an agreed st and ardised collection of outcomes – a “ core outcomes set ” – for all trials in a specific clinical area.1 Recognising that the current inconsistency is a serious hindrance to progress in our specialty , the editors of over 50 journals related to women 's health have come together to support The CROWN ( CoRe Outcomes in WomeN 's health ) Initiative ( Box 1 ) . ! [Graphic][1 ] Box 1 # # # Aims of The CROWN Initiative ( http://www.crown-initiative.org ) 1 . Form a consortium among all gynaecology-obstetrics and related journals to promote core outcome sets in all areas of our specialty . … [ 1 ] : Background Natural estrogen decline leads to vasomotor symptoms ( VMS ) . Hormone therapy alleviates symptoms but increases cancer risk . Effective treatments against VMS with minimal cancer risks are needed . We investigate the effects of a highly bioavailable aglycone rich Red Clover isoflavone treatment to alleviate existing menopausal VMS , assessed for the first time by 24hour ambulatory skin conductance ( SC ) Methods and results We conducted a parallel , double blind , r and omised control trial of 62 peri-menopausal women aged 40–65 , reporting ≥ 5 hot flushes/day and follicle stimulating hormone ≥35 IU/L. Participants received either twice daily treatment with bioavailable RC extract ( RCE ) , providing 34 mg/d isoflavones and probiotics , or masked placebo formulation for 12 weeks . The primary outcome was change in daily hot flush frequency ( HFF ) from baseline to 12 weeks using 24hr SC . Secondary outcomes were change in SC determined hot flush intensity ( HFI ) , self-reported HFF ( rHFF ) and hot flush severity ( rHFS ) , blood pressure and plasma lipids . A significant decrease in 24hr HFF ( P < 0.01 ) and HFI ( P<0.05 ) was found when comparing change from baseline to 12 months of the RCE ( -4.3 HF/24hr , CI -6.8 to -2.3 ; -12956 μS s-1 , CI -20175 to -5737 ) with placebo ( 0.79 HF/24hr , CI -1.56 to 3.15 ; 515 μS s-1 , CI -5465 to 6496 ) . rHFF was also significantly reduced ( P < 0.05)in the RCE ( -2.97 HFs/d , CI -4.77 to -1.17 ) group compared to placebo ( 0.036 HFs/d , CI -2.42 to 2.49 ) . Other parameters were non-significant . RCE was well tolerated . Conclusion Results suggest that moderate doses of RCE were more effective and superior to placebo in reducing physiological and self-reported VMS . Findings support that objective physiological symptom assessment methods should be used together with self-report measures in future studies on menopausal VMS . Trial registration Clinical Trials.gov CONTEXT St and ard therapy for hot flashes has been hormone replacement with estradiol or progestational agents , but recent data suggest that antidepressants inhibiting serotonin reuptake may also be effective . OBJECTIVE To evaluate a selective serotonin reuptake inhibitor ( paroxetine controlled release [ CR ] ) in treating the vasomotor symptoms displayed by a general cross-section of menopausal women . DESIGN AND SETTING R and omized , double-blind , placebo-controlled , parallel group study conducted across 17 US sites , including urban , suburban , and rural clinics . PATIENTS A total of 165 menopausal women aged 18 years or older experiencing at least 2 to 3 daily hot flashes and must have discontinued any hormone replacement therapy for at least 6 weeks . Women were excluded if they had any signs of active cancer or were undergoing chemotherapy or radiation therapy . INTERVENTION After a 1-week placebo run-in phase , study participants were r and omized to receive placebo or receive 12.5 mg/d or 25.0 mg/d of paroxetine CR ( in a 1:1:1 ratio ) for 6 weeks . MAIN OUTCOME MEASURES Mean change from baseline to week 6 in the daily hot flash composite score ( frequency x severity ) . RESULTS Fifty-six participants were r and omly assigned to receive placebo and 51 to receive 12.5 mg/d and 58 to receive 25.0 mg/d of paroxetine CR . The mean reductions in the hot flash frequency composite score from baseline to week 6 were statistically significantly greater for those receiving paroxetine CR than for those receiving placebo . By week 6 , the mean daily hot flash frequency went from 7.1 to 3.8 ( mean reduction , 3.3 ) for those in the 12.5-mg/d and from 6.4 to 3.2 ( mean reduction , 3.2 ) for those in the 25-mg/d paroxetine CR groups and from 6.6 to 4.8 ( mean reduction , 1.8 ) for those in the placebo group . Mean placebo-adjusted reduction in hot flash composite scores were -4.7 ( 95 % confidence interval , - 8.1 to -1.3 ; P = .007 ) comparing 12.5-mg/d paroxetine CR with placebo ; and -3.6 ( 95 % confidence interval , -6.8 to -0.4 ; P = .03 ) comparing 25.0-mg/d paroxetine CR with placebo . This corresponded to median reductions of 62.2 % for those in the 12.5-mg/d and 64.6 % for those in the 25.0-mg/d paroxetine CR groups compared with 37.8 % for those in the placebo group . CONCLUSION Paroxetine CR may be an effective and acceptable alternative to hormone replacement and other therapies in treating menopausal hot flash symptoms OBJECTIVE To evaluate the efficacy comparison of Pueraria mirifica ( PM ) , name in Thai is Kwao Kruea Khao , against conjugated equine estrogen ( CEE ) with/without medroxyprogesterone acetate ( MPA ) in the treatment of perimenopuasal women with climacteric symptoms . MATERIAL AND METHOD Perimenopausal women attending the Menopausal clinic of Hat Yai Regional Hospital were voluntarily recruited . The vasomotor symptoms such as hot flushes and night sweats , as well as other unpleasant symptoms , urogenital and psychological symptoms , were also assessed . Patients were voluntarily enrolled and r and omly received daily 50 mg raw material of PM , Group A , or daily 0.625 mg of conjugated equine estrogen ( CEE ) with/without 2.5 mg of medroxyprogesterone acetate ( MPA ) , Group B , depend on non-hysterectomized/hysterectomized condition . RESULTS Seventy-one patients were enrolled . Eleven of those were excluded for failing to complete the initial work-up and follow-up . Sixty cases were evaluated , 30 cases in Group A Output:	There is substantial variation in how menopausal vasomotor symptoms have been reported and measured in treatment trials .
MS22196	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background : The administration of analgesics to patients with acute abdominal pain due to acute appendicitis is controversial . A study was undertaken to assess the analgesic effect of morphine in patients with acute appendicitis . Methods : A r and omised double-blind clinical trial was conducted in Sina hospital , a general teaching hospital , from January 2004 to March 2005 . Patients scheduled for appendectomy were r and omised to receive 0.1 mg/kg morphine sulfate or saline ( 0.9 % ) to a maximum dose of 10 mg over a 5 min period . Patients were examined by surgeons not involved in their care before and after drug administration and their pain intensity and signs were recorded at each visit . The physicians were also asked to indicate their own treatment plan . The main outcome measures were pain intensity using a visual analogue scale ( VAS ) and signs of acute appendicitis . A favourable reduction in VAS score was defined as a change of > 13 mm . Results : Of the 71 patients enrolled in the study , 35 were allocated to receive morphine and 36 to receive placebo . One patient left the hospital before receiving morphine . No significant differences were seen between the two groups with regard to age , sex and initial VAS score . A more favourable change in VAS score was reported in the morphine group with a significantly greater reduction in the median VAS score than in the placebo group . Morphine administration did not cause significant changes in patients ’ signs or in the physicians ’ plans or diagnoses . No adverse events were seen in either group . Conclusion : Morphine can reduce pain in patients with acute appendicitis without affecting diagnostic accuracy . Trial registration number : NCT00477061 BACKGROUND Acute and chronic pain is common in hospitalized demented elderly people , yet there are limited data about the performance of pain assessment tools in this population . The aim of this study was to evaluate the feasibility and reliability of four pain self- assessment scales in this population and compare their performance to an observational pain rating scale . METHODS Our prospect i ve clinical study was conducted in an acute-care and intermediate-care geriatric hospital on 160 consecutive inpatient referrals to the dementia consultation who met Diagnostic and Statistical Manual of Mental Disorders-IV criteria for dementia . Exclusion criteria were delirium , terminal care , and severe sensory impairment . Four unidimensional self- assessment tools -- the verbal , horizontal visual , vertical visual , and faces pain scales -- were administered in r and omized order to mild , moderate , and severely demented patients . An observational pain rating scale was independently completed by the nursing team . RESULTS Only 12 % of the 160 patients ( mean age 85 years , 71 % women ) understood no scale . Respectively , 97 % , 90 % , and 40 % of patients with mild , moderate , and severe dementia understood at least one scale ( p < .05 ) . There was a nonsignificant trend toward poorer comprehension of the faces scale . Test-retest reliability was high for all four self- assessment scales , and the correlation between these scales was very strong ( Spearman 's r(s ) = 0.81 - 0.95 ; p < .001 ) . Observational rating correlated moderately with self- assessment and tended to underestimate pain intensity ( r(s ) = 0.31 - 0.40 ; p < .05 ) . CONCLUSIONS Self- assessment pain scales can be used reliably in the vast majority of older hospitalized patients with mild to moderate dementia and in nearly half of those with severe dementia . Observational pain rating scales correlate only moderately with self- assessment and should be reserved for those few patients who have demonstrated that they can not complete a self- assessment To determine whether reliable and valid rankings of pain and discomfort result ing from hospital procedures encountered by advanced dementia patients could be developed from interviews with cognitively intact adults , rankings of pain and discomfort result ing from 16 common procedures were obtained from two sample s of hospitalized , nondemented adults using ten- ( N = 100 ) and five- ( N = 35 ) point numeric rating scales ( NRS ) . Reliability was assessed by having 30 additional subjects complete ten-point NRS representing the ten most frequent procedures in a re-arranged order . By repeated measure analysis of variance , the scales discriminated between procedures ( F = 35.1 , P < 0.001 ) . Subjects could discriminate between pain and discomfort ( F = 21.6 , P < 0.001 ) . The five-point NRS exhibited better subject discrimination between experiences . Reliability was also acceptable . A five-point NRS produced reliable and valid pain and discomfort rankings for 16 common hospital procedures and experiences . These rankings should prove useful in reducing suffering and can serve as surrogates for quantifying pain and discomfort in dementia patients BACKGROUND Universal pain screening with a 0–10 pain intensity numeric rating scale ( NRS ) has been widely implemented in primary care . OBJECTIVE To evaluate the accuracy of the NRS as a screening test to identify primary care patients with clinical ly important pain . DESIGN Prospect i ve diagnostic accuracy study PARTICIPANTS 275 adult clinic patients were enrolled from September 2005 to March 2006 . MEASUREMENTS We operationalized clinical ly important pain using two alternate definitions : ( 1 ) pain that interferes with functioning ( Brief Pain Inventory interference scale ≥ 5 ) and ( 2 ) pain that motivates a physician visit ( patient-reported reason for the visit ) . RESULTS 22 % of patients reported a pain symptom as the main reason for the visit . The most common pain locations were lower extremity ( 21 % ) and back/neck ( 18 % ) . The area under the receiver operator characteristic curve for the NRS as a test for pain that interferes with functioning was 0.76 , indicating fair accuracy . A pain screening NRS score of 1 was 69 % sensitive ( 95 % CI 60–78 ) for pain that interferes with functioning . Multilevel likelihood ratios for scores of 0 , 1–3 , 4–6 , and 7–10 were 0.39 ( 0.29–0.53 ) , 0.99 ( 0.38–2.60 ) , 2.67 ( 1.56–4.57 ) , and 5.60 ( 3.06–10.26 ) , respectively . Results were similar when NRS scores were evaluated against the alternate definition of clinical ly important pain ( pain that motivates a physician visit ) . CONCLUSIONS The most commonly used measure for pain screening may have only modest accuracy for identifying patients with clinical ly important pain in primary care . Further research is needed to evaluate whether pain screening improves patient outcomes in primary care Abstract The present study investigated whether the level of cognitive impairment ( CI ) affects acute pain behavior and how it is manifested . Participants were 159 individuals ( mean age 42 ± 12 ) , 121 with CI ( divided into four groups according to the level of CI : mild , moderate , severe , profound ) and 38 with normal cognition ( controls ) . The behavior of the participants before and during acute pain ( influenza vaccination ) was coded by two raters with the Facial Action Coding System ( FACS – scores facial reactions to pain ) and the Non‐Communicating Children ’s Pain Checklist ( NCCPC‐R – scores both facial and general body reactions ) . Individuals with severe – profound CI exhibited elevated FACS and NCCPC‐R values at baseline compared with all other groups ( p < 0.01 ) . Both FACS and NCCPC‐R scores of individuals with mild – moderate CI and controls increased significantly during vaccination ( p < 0.001 ) . In contrast , individuals with severe – profound CI exhibited high rates of “ freezing reaction ” ( stillness ) during vaccination , manifested mainly in the face and therefore result ing in elevation of only NCCPC‐R scores but not of FACS ’s . The results suggest that the level of CI affects baseline as well as pain behavior and it is therefore necessary to choose an appropriate behavioral tool to measure pain in these individuals accordingly . For example , tools based on facial reactions alone might provide the false impression that individuals with severe – profound CI are insensitive to pain ( due to freezing ) OBJECTIVES To evaluate the effect of emergency department ( ED ) crowding on assessment and treatment of pain in older adults . DESIGN Retrospective review of ED records from a prospect i ve cohort study . SETTING Urban , academically affiliated , tertiary medical center . PARTICIPANTS One hundred fifty-eight patients , aged 50 and older , evaluated and hospitalized from the ED with hip fracture . MEASUREMENTS Patient-related risk factors : age , sex , nursing home residence , ED triage status , dementia , Acute Physiology in Age and Chronic Health Evaluation II physiological score , and R AND comorbidity score . ED crowding risk factors : ED census and mean length of stay . OUTCOMES documentation of pain assessment , time to pain assessment , time to pain treatment , patients reporting pain receiving analgesia , and meperidine use . RESULTS Mean age was 83 ( range 52 - 101 ) , 81.0 % of patients complained of pain , mean time to pain assessment was 40 minutes ( range 0 - 600 ) , time to treatment was 141 minutes ( range 10 - 525 ) , and mean delay to treatment was 122 minutes ( range 0 - 526 ) . Of those with pain , 35.9 % received no analgesia , 7.0 % received nonopioids , and 57.0 % received opioids . Of those receiving opioids , 32.8 % received meperidine . ED crowding at census levels greater than 120 % bed capacity was significantly associated with a lower likelihood of documentation of pain assessment ( P = .05 ) and longer times to pain assessment ( P = .01 ) . CONCLUSION Older adults with hip fracture are at risk for under assessment of pain , considerable delays in analgesic administration after pain is identified , and treatment with inappropriate analgesics ( e.g. , meperidine ) in the ED . Higher levels of ED census are significantly associated with poorer pain management BACKGROUND Successfully managing pain for the trauma patient decreases morbidity , improves patient satisfaction , and is an essential component of critical care . Using patient-controlled analgesia ( PCA ) morphine to control pain may be complicated by concerns of respiratory depression , hemodynamic instability , addiction , urinary retention , and drug-induced ileus . Morphine is rapidly absorbed by mucosal surfaces in the respiratory tract , achieving systemic concentrations equal to 20 % of equivalent intravenous doses . The purpose of this study was to evaluate the safety , efficacy , and utility of nebulized morphine in patients with posttraumatic thoracic pain . METHODS This double-blinded , prospect i ve study r and omized patients with severe posttraumatic thoracic pain into two groups . The experimental group ( NMS ) received nebulized morphine every 4 hours and normal saline by PCA . The control group ( PCA ) received nebulized saline every 4 hours and morphine by PCA . Dose adjustments were made based on patient response to treatments using a 10-point visual analog scale ( VAS ) for pain . Pulmonary function , pain relief ( VAS ) , level of sedation ( 0 - 3 ) , total drug administration , and systematic side effects were recorded . RESULTS Forty-four patients were r and omized ( 22 per group ) . Seven hundred seventy observations were made . The mean 4-hour dose of morphine was 11.96 + /- 3.4 mg for NMS and 6.22 + /- 4.7 mg for PCA ( p < 0.001 ) . Patients with NMS had lower heart rates compared with PCA ( 79 + /- 11 bpm versus 92 + /- 12 bpm ; p < 0.001 ) and were less se date d ( 0.33 + /- 0.7 versus 0.56 + /- 0.9 ; p = 0.03 ) . The mean pain level ( VAS ) was 3.38 + /- 1.8 for NMS and 3.84 + /- 2.7 for PCA ( p = 0.2 ) . There was no difference between pain levels before and after dosing . There were no differences between groups with respect to arterial blood pressure , respiratory rate , vital capacity , mean forced expiratory volume in 1 second , spirometric volumes , or Sao2 . CONCLUSION Nebulized morphine can be safely and effectively used to control posttraumatic thoracic pain . Pain can be successfully managed while vital capacity , mean forced expiratory volume in one second , and spirometric volumes are maintained . Compared with PCA morphine , nebulized morphine provides equivalent pain relief with less sedative effects OBJECTIVE The objective of this study was to identify the underlying causes of respiratory-related critical events associated with intravenous patient-controlled analgesia ( i.v . PCA ) . DESIGN The design is an observation study of prospect ively collected data . SETTING An Acute Pain Service ( APS ) was established for the management of all patients receiving i.v . PCA therapy for pain management . As part of ongoing care , all respiratory-related critical events were documented and analyzed by staff members of the APS team . PATIENTS All patients receiving i.v . PCA therapy through the APS during the period of May 1990 through October 1992 were enrolled in the study . INTERVENTIONS Evaluation of all respiratory-related critical events was attempted to identify the underlying cause of the event and to determine if measures could be taken to prevent recurrence of similar events . OUTCOME MEASURES Any clinical event that could have or did lead to adverse patient outcome was used as an outcome measure . RESULTS A total of 3,785 patients received P Output:	RESULTS We found no evidence that directly linked the timing , frequency , or method of pain assessment with outcomes or safety in medical in patients . There is good evidence that treating abdominal pain does not compromise timely diagnosis and treatment of the surgical abdomen . Pain management teams and other systemwide interventions improve assessment and use of analgesics , but do not clearly affect pain outcomes . The safety and effectiveness of PCA in medical patients have not been studied . There is weak evidence that most cognitively impaired individuals can underst and at least one self- assessment measure . Almost no evidence is available to guide management of pain in delirium . Pain is a prevalent problem for medical in patients .
MS22197	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Purpose To determine if particular values clarification exercises included in a patient decision aid had discernible impact on postdecisional regret in patients with early-stage prostate cancer . Methods A multicenter r and omized controlled trial compared 2 versions of a computerized patient decision aid : only structured information compared to the structured information plus values clarification exercises . Assessment s were conducted during the decision aid visit ; telephone follow-up interviews were conducted when patients made their decisions with their physician , 3 months after completing treatment , and > 1 year later ( per a mailing ) . Outcome measures included the Decisional Conflict Scale , the Preparation for Decision Making Scale , and the Decision Regret Scale . Results A total of 156 patients participated , 75 provided information only and 81 provided information plus values clarification exercises . The groups did not differ significantly on any outcome evaluated at the decision aid visit ; in both groups , decisional conflict decreased immediately after using the decision aid . Between-group differences emerged after the decision was actually made . The values clarification exercises group reported higher Preparation for Decision Making Scale scores at the decision follow-up and at the > 1-year follow-up . Regret did not differ significantly between groups at the 3-month follow-up but was lower for the values clarification exercises group than for the information group at the > 1-year follow-up . Conclusion The results suggest that the values clarification exercises led to better preparation for decision making and to less regret . The impact , however , only emerged after the decision was made Background : Fertility is a priority for many young women with breast cancer . Women need to be informed about interventions to retain fertility before chemotherapy so as to make good quality decisions . This study aim ed to prospect ively evaluate the efficacy of a fertility-related decision aid ( DA ) . Methods : A total of 120 newly diagnosed early-stage breast cancer patients from 19 Australian oncology clinics , aged 18–40 years and desired future fertility , were assessed on decisional conflict , knowledge , decision regret , and satisfaction about fertility-related treatment decisions . These were measured at baseline , 1 and 12 months , and were examined using linear mixed effects models . Results : Compared with usual care , women who received the DA had reduced decisional conflict ( β=−1.51 ; 95%CI : −2.54 to 0.48 ; P=0.004 ) and improved knowledge ( β=0.09 ; 95%CI : 0.01–0.16 ; P=0.02 ) , after adjusting for education , desire for children and baseline uncertainty . The DA was associated with reduced decisional regret at 1 year ( β=−3.73 ; 95%CI : −7.12 to −0.35 ; P=0.031 ) , after adjusting for education . Women who received the DA were more satisfied with the information received on the impact of cancer treatment on fertility ( P<0.001 ) , fertility options ( P=0.005 ) , and rated it more helpful ( P=0.002 ) , than those who received st and ard care . Conclusion : These findings support widespread use of this DA shortly after diagnosis ( before chemotherapy ) among younger breast cancer patients who have not completed their families Background : To examine the impact of race on treatment regret among men with recurrent prostate cancer after surgery or radiation . Methods : The prospect i ve Comprehensive , Observational , Multicenter , Prostate Adenocarcinoma ( COMPARE ) registry was used to study a cohort of 484 men with biochemically recurrent prostate cancer after radical prostatectomy , external beam radiation or brachytherapy . Multivariable logistic regression was used to model the association between race and treatment regret and to determine whether there was an interaction between race and sexual problems after treatment with regards to treatment regret . Results : Black men ( N=78 ) were significantly more likely to have treatment regret when compared with non-black men ( N=406 ; 21.8 % versus 12.6 % ) on univariable analysis ( odds ratio ( OR ) 1.94 ; 95 % confidence interval 1.05–3.56 ; P=0.03 ) . On multivariable analysis , black race trended towards but was no longer significantly associated with an increase in treatment regret ( adjusted OR ( AOR ) 1.84 ( 0.95–3.58 ) ; P=0.071 ) . There was an interaction between race and sexual problems after treatment ( Pinteraction=0.02 ) such that among those without sexual problems , black men had more treatment regret than non-black men ( 26.7 % versus 8.4 % : AOR 4.68 ( 1.73–12.63 ) ; P=0.002 ) , whereas among those with sexual problems , there was no difference in treatment regret between black and non-black men ( 18.8 % versus 17.3 % : AOR 1.04 ( 0.44–2.46 ) ; P=0.93 ) . Conclusions : Among men with recurrent prostate cancer after surgery or radiation , black men were nearly twice as likely to experience treatment regret . Treating physicians should ensure that patients are fully apprised of the pros and cons of all treatment options to reduce the risk of subsequent regret PURPOSE Breast cancer ( BC ) decision aid ( DA ) r and omized studies are limited to DA use in consultations among Western population s and for primary surgery . Their effectiveness beyond consultations , for reconstructive surgery and in other population s , has not been evaluated . We developed a DA administered after consultation for Chinese women deciding on BC surgery and , where relevant , immediate breast reconstruction , which was evaluated in this r and omized controlled trial ( RCT ) . PATIENTS AND METHODS Overall , 276 women considering BC surgery for early-stage BC were r and omly assigned to receive a DA ( take-home booklet ) or the st and ard information booklet ( control condition ) after the initial consultation , wherein surgeons disclosed the diagnosis and discussed treatment options with patients . Using block r and om assignment by week , 138 women were assigned to the DA arm and 138 to the control arm . Participants completed interview-based question naires 1 week after consultation and then 1 , 4 , and 10 months after surgery . Primary outcome measures were decisional conflict , decision-making difficulties , BC knowledge 1 week after consultation , and decision regret 1 month after surgery . Secondary outcome measures were treatment decision , decision regret 4 and 10 months after surgery , and postsurgical anxiety and depression . RESULTS The DA group reported significantly lower decisional conflict scores 1 week after consultation ( P = .016 ) compared with women in the control arm . Women receiving the DA had significantly lower decision regret scores 4 ( P = .026 ) and 10 months ( P = .014 ) after surgery and lower depression scores 10 months after surgery ( P = .001 ) . CONCLUSION This RCT demonstrated DAs may benefit Chinese patients in Hong Kong by reducing decisional conflict and subsequent regret and enhance clinical services for this population PURPOSE Underst and ing the distinctive patterns of treatment-related dysfunction after alternative initial treatments for early prostate cancer ( PC ) may improve patients ' choice of treatment and later help them adjust to its consequences . We characterized the time course of treatment complications while adjusting for potentially confounding pretreatment factors hindering other observational studies . PATIENTS AND METHODS In a prospect i ve cohort study of 417 men we assessed urinary , bowel , and sexual function from before primary treatment to 24 months after . To control for potential confounding , we measured sociodemographic and PC prognostic factors , medical comorbidity , and pretreatment function commonly affected by PC and its treatment . RESULTS Patients who underwent external beam radiotherapy ( EBRT ) , radical prostatectomy ( RP ) , and brachytherapy ( BT ) differed significantly in sociodemographic factors , cancer prognostic factors , and pretreatment symptom status , especially sexual function . Urinary incontinence increased sharply after RP , while bowel problems and urinary irritation/obstruction rose after EBRT and BT . Sexual dysfunction increased in all patients , particularly after radical prostatectomy , and nerve-sparing surgical technique had little apparent benefit . There was no change in urinary function and little change in overall bowel function after 12 months , but the time course of sexual dysfunction varied by treatment and , for bowel function , by symptom . Multiple regression modeling confirmed that treatment influences all 24-month outcomes , but residual confounding persisted . CONCLUSION Pretreatment function and the primary treatment modality for early stage PC strongly predict the affected organ systems and time course of dysfunction . With this information , patients and their physicians may refine their choice of treatment and better anticipate its consequences OBJECTIVE To describe relationships between use of the Personal Patient Profile-Prostate ( P3P ) decision support system and patient characteristics , and perceived preparation for decision making ( PrepDM ) , satisfaction and decisional regret in the context of prostate cancer treatment choice . METHODS 494 men with localized prostate cancer ( LPC ) were r and omized to receive the P3P intervention or usual care and completed pre-treatment , 1-month and 6-month outcome measures . Multivariable linear regression models were fit for each outcome . RESULTS Physician consult visits prior to enrollment , race/ethnicity , and use of clinic-provided books were significant predictors of perceived PrepDM at 1 month . Prior Internet use and PrepDM significantly predicted 6-month decision satisfaction . Decisional regret was significantly predicted by demographics , anxiety , PrepDM score , and EPIC bowel domain score at 6 months . Use of P3P did not predict any outcome . CONCLUSION While the P3P intervention did not significantly affect the outcomes , pre-enrollment information and preparation were strong predictors of the 1- and 6-month outcomes . Decision regret was significantly influenced by personal characteristics and post-treatment symptoms/side effects . PRACTICE IMPLICATION S Information received and used between biopsy and the treatment options consult visit is likely to make a difference in decision satisfaction OBJECTIVE To investigate the effect of including an online decision aid ( DA ) during prostate cancer treatment counseling on decisional regret and information satisfaction in a one-year follow-up . METHODS Within a cluster RCT , 18 Dutch hospitals were r and omized to DA counseling or care-as-usual , patients ( n = 382 ) initially completed question naires directly after treatment decision making . Six and twelve months later regret ( Decisional Regret Scale ) and information satisfaction ( SCIP-B ) were assessed . Anxious and depressive symptoms ( HADS ) was included as possible covariate . RESULTS After 12 months , 43 participants ( 15 % ) regretted their treatment choice and 105 participants ( 36 % ) were dissatisfied with the information that was received at the time of decision-making , regardless of being exposed to the DA . Anxious and depressive symptoms at follow-up were associated with regret and information dissatisfaction . CONCLUSION No long-term benefical effects emerged from DA usage compared to patients who underwent st and ard counseling . PRACTICE IMPLICATION S During PCa treatment counseling , healthcare providers should be aware of anxious and depressive symptoms Effect sizes are the currency of psychological research . They quantify the results of a study to answer the research question and are used to calculate statistical power . The interpretation of effect sizes — when is an effect small , medium , or large ?— has been guided by the recommendations Jacob Cohen gave in his pioneering writings starting in 1962 : Either compare an effect with the effects found in past research or use certain conventional benchmarks . The present analysis shows that neither of these recommendations is currently applicable . From past publications without pre- registration , 900 effects were r and omly drawn and compared with 93 effects from publications with pre- registration , revealing a large difference : Effects from the former ( median r = 0.36 ) were much larger than effects from the latter ( median r = 0.16 ) . That is , certain biases , such as publication bias or question able research practice s , have caused a dramatic inflation in published effects , making it difficult to compare an actual effect with the real population effects ( as these are unknown ) . In addition , there were very large differences in the mean effects between psychological sub-disciplines and between different study design s , making it impossible to apply any global benchmarks . Many more pre-registered studies are needed in the future to derive a reliable picture of real population effects In this prospect i ve , longitudinal study the authors examined changes in cognitive , emotional , and interpersonal components of prostate cancer-related quality of life in 71 men who underwent robotic-assisted prostatectomy for prostate cancer . They identified significant changes across several quality -of-life domains from presurgery to 3-months and 1-year postsurgery . Although some components of quality of life returned to baseline by one year postsurgery , decrements in sexual intimacy , sexual confidence , and masculine self-esteem were enduring . These data can be used to guide patients in their expectations for quality of life following robotic prostatectomy and highlight the need for multidisciplinary approaches aim ed at improving men 's sexual adjustment after this procedure PURPOSE Hypospadias repair is a commonly performed procedure . Little is known about decisional regret in parents who agree to proceed with this surgical reconstruction . We present data on this previously underexplored issue . MATERIAL S AND METHODS We performed followup analysis of 100 couples prospect ively evaluated after counseling for surgical correction of distal hypospadias in their son with assessment of complications and decisional regret 1 year after surgery . Findings were contrasted with baseline demographics , hypospadias knowledge and decisional conflict at the time of counseling . RESULTS Decisional regret was found in 116 parents , including mild regret in 41.4 % and moderate to severe regret in 8.6 % . There was no statistically significant difference in paired regret analysis between mothers and fathers . Complications were strongly associated with decisional regret ( p < 0.001 ) . On regression analysis postoperative complications ( OR 14.7 , 95 % CI 1.6 - 131. Output:	Longitudinal effects can influence the expression of decision regret , yet many studies are not design ed to collect long-term data ; prostate cancer studies may be particularly disadvantaged .
MS22198	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Introduction Since digital subtraction angiography ( DSA ) carries a low risk of morbidity , and is associated with patient discomfort and higher cost , our objective was to determine whether high-resolution 3-D time-of-flight MR angiography ( TOF-MRA ) at 3 T may replace DSA in the follow-up of patients after coiling of an intracranial aneurysm . Methods This prospect i ve study included 50 consecutive patients with a ruptured and subsequently coiled intracranial aneurysm . All patients were followed up at a mean of 14 months after coiling with DSA and high-resolution 3-D TOF-MRA at 3 T generating 0.02 mm3 isotropic voxels . One examiner used DSA and TOF-MR angiograms to assess the need for and risk of retreatment ; these data were used to calculate intermodality agreement . Another two examiners independently assessed aneurysm occlusion by DSA and TOF-MRA according to the Raymond scale ; these data were used to calculate interobserver agreement . Results Discrepancies between DSA and TOF-MRA were found in three patients ( intermodality agreement κ = 0.86 ) . While DSA indicated complete aneurysm occlusion , TOF-MRA showed small neck remnants in the three patients . Coils on all DSA projections obscured these three neck remnants . Interobserver agreement was higher for DSA ( κ = 0.82 ) than for TOF-MRA ( κ = 0.68 ) , which was in part due to the complexity of the information provided by TOF source images and reconstructions . Conclusion 3-D TOF-MRA at 3 T is not only an adjunctive tool but is ready to replace DSA in the follow-up of patients with previously coiled intracranial aneurysms . Additional DSA may only be performed in complex and not clearly laid out aneurysms BACKGROUND AND PURPOSE Digital subtraction angiography ( DSA ) is used to follow-up intracranial aneurysms treated with detachable coils to identify recurrence and determine need for additional treatment . However , DSA is invasive and involves a small risk of neurologic complications . We assessed the feasibility and usefulness of 3D time-of-flight ( TOF ) MR angiography ( MRA ) performed at 3 T compared with DSA for the follow-up of coil-treated intracranial aneurysms . METHODS In a prospect i ve study , 20 consecutive patients with 21 intracranial aneurysms treated with coils underwent DSA and nonenhanced and enhanced multiple overlapping thin-slab acquisition 3D TOF MRA at 3 T on the same day at a mean follow-up of 6 months ( range , 4 - 14 months ) after coil placement . MRA images were evaluated for presence of artifacts , presence and size of aneurysm remnants and recurrences , patency of parent and branch vessels , and added value of contrast material enhancement . MRA and DSA findings were compared . RESULTS Interobserver agreement of MRA was good , as was agreement between MRA and DSA . All three recurrences that needed additional treatment were detected with MRA . Minor disagreement occurred in four cases : three coil-treated aneurysms were scored on MRA images as having a small remnant , whereas on DSA images these aneurysms were occluded ; the other aneurysm was scored on MRA images as having a small remnant , whereas on DSA images this was a small recurrence . Use of contrast material had no additional value . Coil-related MR imaging artifacts were minimal and did not interfere with evaluation of the occlusion status of the aneurysm . CONCLUSION High-spatial-resolution 3D TOF MRA at 3 T is feasible and useful in the follow-up of patients with intracranial aneurysms treated with coil placement Background and Purpose — The purpose of this study was to estimate the performance measures of MR angiography ( MRA ) in the diagnosis of aneurysm residual flow after coil occlusion . Methods — Patients having at least 1 cerebral aneurysm treated with coil occlusion were prospect ively and consecutively enrolled . Time of flight and contrast-enhanced MRA were performed the same day of the DSA follow-up . The degree of aneurysm occlusion and dimensions of the residual flow were evaluated by independent readers at MRA and digital subtraction angiogram . MRA performance measures were estimated in a cross-sectional analysis and repeated in subgroups of aneurysm sizes and locations . MRA predictive values for recurrence were also estimated using a longitudinal design . Results — We obtained 167 aneurysm evaluations for each imaging modality . Class 3 residual flow was seen on digital subtraction angiogram follow-up in 27 % . The sensitivity and specificity of MRA was 88 % ( 95 % CI , 80–94 ) and 79 % ( 95 % CI , 67–88 ) , respectively . The positive predictive value for a Class 3 recurrence was 67 % ( 95 % CI , 51–80 ) and the negative predictive value was 93 % ( 95 % CI , 86–97 ) . Time-of-flight MRA underestimated the length of the residual flow ( P=0.039 ) , whereas contrast-enhanced MRA overestimated its width ( P<0.0001 ) . MRA sensitivity for a Class 3 residual flow was lower for aneurysms < 6 mm ( P=0.01 ) . Conclusions — MRA has sufficient accuracy for screening of aneurysm residual flow after coil occlusion . Due to its lower negative predictive value , recurrent aneurysms should be confirmed with digital subtraction angiogram before planning a retreatment . Routine use of MRA to follow small aneurysms should wait better estimation of its performance in this particular subgroup Background and Purpose — We sought to better define the morbidity of endovascular Guglielmi detachable coil ( GDC ) treatment of unruptured cerebral aneurysms and to discuss its role in the prevention of subarachnoid hemorrhage . Methods — We conducted an observational study from August 1992 to June 1999 of 125 unruptured aneurysms treated with GDC in 116 patients : 91 women ( 78.4 % ) and 25 men ( 21.6 % ) , aged 30 to 78 years ( mean age , 50.6 years ) . Immediate and late clinical results were recorded for any neurological event or hemorrhage related to the treated unruptured aneurysm . Angiographic results are reported as immediate , early ( 2 to 12 months ) , intermediate ( 12 to 30 months ) , and late follow-up ( > 30 months ) . Results — Immediate angiographic results showed complete obliteration ( class 1 ) in 59 ( 47.2 % ) or residual neck ( class 2 ) in 53 aneurysms ( 42.4 % ) , leaving 6 residual aneurysms ( 4.8 % ) and 7 failures ( 5.6 % ) . Early follow-up angiograms , available in 100 treated aneurysms ( 84 % ) , revealed class 1 in 52 % and class 2 in 41 % . Intermediate angiograms , available in 53 aneurysms ( 44.5 % ) , showed class 1 in 47.2 % and class 2 in 43.4 % , while late results , available in 37 lesions ( 31.1 % ) , had class 1 and 2 in 48.6 % and 37.8 % , respectively . Six patients suffered a permanent neurological deficit at last follow-up ( 5.2 % ) , with a good outcome in 5 patients and fair outcome in 1 patient . There was no mortality . There was no aneurysmal rupture during a mean clinical follow-up of 32.1 months . Conclusions — Endovascular treatment with GDC for unruptured aneurysms is relatively safe . Its role in the prevention of aneurysmal rupture remains to be determined , preferably by a r and omized study BACKGROUND AND PURPOSE : Blood-pool agents are promising in the imaging of small vessels with slow or complex flow . Our aim was to compare blood-pool contrast-enhanced MR angiography ( BPCE-MRA ) using gadofosveset trisodium ( Vasovist ) with 3D time-of-flight MRA ( TOF-MRA ) in the follow-up of intracranial aneurysms after endovascular therapy . MATERIAL S AND METHODS : We included 32 patients with a total of 37 coiled aneurysms . MRAs in the early steady-state phase were performed on a 1.5 T scanner within 8 days of digital subtraction angiography ( DSA ) . Two radiologists independently analyzed TOF-MRA and BPCE-MRA images . Consensus was reached by review involving a third neuroradiologist . DSA images were interpreted separately by an interventional radiologist . Findings were assigned to 1 of 3 categories : 1 ) complete occlusion , 2 ) residual neck , and 3 ) residual aneurysm . RESULTS : Follow-up DSA demonstrated 13 complete obliterations ( class 1 ) , 13 residual necks ( class 2 ) , and 11 residual aneurysms ( class 3 ) . Weighted κ statistics showed substantial concordance of TOF-MRA and DSA ( 0.664 ) as well as BPCE-MRA and DSA ( 0.724 ) ratings . Comparison between TOF-MRA and BPCE-MRA found excellent agreement ( 0.818 ) with only 6 ( 16.2 % ) discrepancies . For detecting residual flow , the difference in accuracy of both MRA techniques ( 83.8 % versus 91.9 % ) was not significant ( McNemar , P = 1.000 ) . BPCE-MRA showed a tendency towards higher sensitivity and specificity ( 91.7 % and 92.3 % , respectively ) compared with TOF-MRA ( 87.5 % and 76.9 % ) . CONCLUSIONS : In classifying the completeness of endovascular cerebral aneurysm therapy , we found that BPCE-MRA and 3D TOF-MRA showed very good agreement . The use of Vasovist did not lead to a significantly increased accuracy of MRA follow-up BACKGROUND AND PURPOSE : MR angiography ( MRA ) is increasingly used as a noninvasive imaging technique for the follow-up of coiled intracranial aneurysms . However , the need for contrast enhancement has not yet been eluci date d. We compared 3D time-of-flight MRA ( TOF-MRA ) and contrast-enhanced MRA ( CE-MRA ) at 3 T with catheter angiography . MATERIAL S AND METHODS : Sixty-seven patients with 72 aneurysms underwent TOF-MRA , CE-MRA , and catheter-angiography 6 months after coiling . Occlusion status on MRA was classified as adequate ( complete and neck remnant ) or incomplete by 2 independent observers . For TOF-MRA and CE-MRA , interobserver agreement , intermodality agreement , and correlation with angiography were assessed by κ statistics . RESULTS : Catheter-angiography revealed incomplete occlusion in 12 ( 17 % ) of the 69 aneurysms ; 3 aneurysms were excluded due to MR imaging artifacts . Interobserver agreement was good for CE-MRA ( κ = 0.77 ; 95 % confidence interval [ CI ] , 0.55–0.98 ) and very good for TOF-MRA ( κ = 0.89 ; 95 % CI , 0.75–1.00 ) . Correlation of TOF-MRA and CE-MRA with angiography was good . The sensitivity of TOF-MRA and CE-MRA was 75 % ( 95 % CI , 43%–95 % ) ; the specificity of TOF-MRA was 98 % ( 95 % CI , 91%–100 % ) and of CE-MRA , 97 % ( 95 % CI , 88%–100 % ) . All 5 incompletely occluded aneurysms , which were additionally treated , were correctly identified with both MRA techniques . Areas under the receiver operating characteristic curve for TOF-MRA and CE-MRA were 0.90 ( 95 % CI , 0.79–1.00 ) and 0.91 ( 95 % CI , 0.79–1.00 ) . Intermodality agreement between TOF-MRA and CE-MRA was very good ( κ = 0.83 ; 95 % CI , 0.65–1.00 ) , with full agreement in 66 ( 96 % ) of the 69 aneurysms . CONCLUSIONS : In this study , TOF-MRA and CE-MRA at 3 T were equivalent in evaluating the occlusion status of intracranial aneurysms after coiling . Because TOF-MRA does not involve contrast administration , this method is preferred over CE-MRA In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic im Output:	Both TOF-MRA and contrast-enhanced MRA are shown to be highly accurate for detection of any recanalization in intracranial aneurysms treated with endovascular coil occlusion
MS22199	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Dietary n-3 polyunsaturated fatty acids improve brain functioning in animal studies , but there is limited study of whether this type of fat protects against Alzheimer disease . OBJECTIVE To examine whether fish consumption and intake of different types of n-3 fatty acids protect against Alzheimer disease . DESIGN Prospect i ve study conducted from 1993 through 2000 , of a stratified r and om sample from a geographically defined community . Participants were followed up for an average of 3.9 years for the development of Alzheimer disease . PATIENTS A total of 815 residents , aged 65 to 94 years , who were initially unaffected by Alzheimer disease and completed a dietary question naire on average 2.3 years before clinical evaluation of incident disease . MAIN OUTCOME MEASURES Incident Alzheimer disease diagnosed in a structured neurologic examination by means of st and ardized criteria . RESULTS A total of 131 sample participants developed Alzheimer disease . Participants who consumed fish once per week or more had 60 % less risk of Alzheimer disease compared with those who rarely or never ate fish ( relative risk , 0.4 ; 95 % confidence interval , 0.2 - 0.9 ) in a model adjusted for age and other risk factors . Total intake of n-3 polyunsaturated fatty acids was associated with reduced risk of Alzheimer disease , as was intake of docosahexaenoic acid ( 22:6n-3 ) . Eicosapentaenoic acid ( 20:5n-3 ) was not associated with Alzheimer disease . The associations remained unchanged with additional adjustment for intakes of other dietary fats and of vitamin E and for cardiovascular conditions . CONCLUSION Dietary intake of n-3 fatty acids and weekly consumption of fish may reduce the risk of incident Alzheimer disease BACKGROUND Participation in leisure activities has been associated with a lower risk of dementia . It is unclear whether increased participation in leisure activities lowers the risk of dementia or participation in leisure activities declines during the pre clinical phase of dementia . METHODS We examined the relation between leisure activities and the risk of dementia in a prospect i ve cohort of 469 subjects older than 75 years of age who resided in the community and did not have dementia at base line . We examined the frequency of participation in leisure activities at enrollment and derived cognitive-activity and physical-activity scales in which the units of measure were activity-days per week . Cox proportional-hazards analysis was used to evaluate the risk of dementia according to the base-line level of participation in leisure activities , with adjustment for age , sex , educational level , presence or absence of chronic medical illnesses , and base-line cognitive status . RESULTS Over a median follow-up period of 5.1 years , dementia developed in 124 subjects ( Alzheimer 's disease in 61 subjects , vascular dementia in 30 , mixed dementia in 25 , and other types of dementia in 8) . Among leisure activities , reading , playing board games , playing musical instruments , and dancing were associated with a reduced risk of dementia . A one-point increment in the cognitive-activity score was significantly associated with a reduced risk of dementia ( hazard ratio , 0.93 [ 95 percent confidence interval , 0.90 to 0.97 ] ) , but a one-point increment in the physical-activity score was not ( hazard ratio , 1.00 ) . The association with the cognitive-activity score persisted after the exclusion of the subjects with possible pre clinical dementia at base line . Results were similar for Alzheimer 's disease and vascular dementia . In linear mixed models , increased participation in cognitive activities at base line was associated with reduced rates of decline in memory . CONCLUSIONS Participation in leisure activities is associated with a reduced risk of dementia , even after adjustment for base-line cognitive status and after the exclusion of subjects with possible pre clinical dementia . Controlled trials are needed to assess the protective effect of cognitive leisure activities on the risk of dementia CONTEXT Exogenous estrogen use may lower risk of dementia in postmenopausal women . A relationship between long-term exposure to endogenous estrogens and incident dementia has been hypothesized but not studied . OBJECTIVE To determine whether a longer reproductive period , as an indicator of longer exposure to endogenous estrogens , is associated with lower risk of dementia and Alzheimer disease ( AD ) in women who have natural menopause . DESIGN AND SETTING The Rotterdam Study , a population -based prospect i ve cohort study conducted in the Netherl and s. PARTICIPANTS A total of 3601 women aged 55 years or older who did not have dementia at baseline ( 1990 - 1993 ) and had information on age at menarche , age at menopause , and type of menopause . Participants were reexamined in 1993 - 1994 and 1997 - 1999 and were continuously monitored for development of dementia . MAIN OUTCOME MEASURES Incidence of dementia , based on Diagnostic and Statistical Manual of Mental Disorders , Revised Third Edition criteria , and AD , based on National Institute of Neurological Disorders and Stroke/Alzheimer 's Disease and Related Disorders Association criteria , compared by quartiles of reproductive period among women with natural menopause . RESULTS During 21 046 person-years of follow-up ( median follow-up , 6.3 years ) , 199 women developed dementia , including 159 who developed AD . After adjusting for age , dementia was not clearly associated with length of reproductive period . However , after adjusting for multiple covariates , women with natural menopause and more reproductive years had an increased risk of dementia ( adjusted rate ratio [ RR ] for women with > 39 reproductive years [ highest quartile ] compared with < 34 reproductive years [ lowest quartile ] , 1.78 ; 95 % confidence interval [ CI ] , 1.12 - 2.84 ) . The adjusted RR per year of increase was 1.04 ( 95 % CI , 1.01 - 1.08 ) . For risk of AD , the adjusted RRs were 1.51 ( 95 % CI , 0.91 - 2.50 ) and 1.03 ( 95 % CI , 1.00 - 1.07 ) , respectively . Risk of dementia associated with a longer reproductive period was most pronounced in APOE epsilon4 carriers ( adjusted RR for > 39 reproductive years compared with < 34 reproductive years , 4.20 [ 95 % CI , 1.97 - 8.92 ] for dementia and 3.42 [ 95 % CI , 1.51 - 7.75 ] for AD ) , whereas in noncarriers , no clear association with dementia or AD was observed . CONCLUSION Our findings do not support the hypothesis that a longer reproductive period reduces risk of dementia in women who have natural menopause BACKGROUND Few prospect i ve studies have assessed diabetes mellitus as a risk factor for incident Alzheimer disease ( AD ) and decline in cognitive function . OBJECTIVE To evaluate the association of diabetes mellitus with risk of AD and change in different cognitive systems . DESIGN Longitudinal cohort study . PARTICIPANTS For up to 9 years , 824 older ( those > 55 years ) Catholic nuns , priests , and brothers underwent detailed annual clinical evaluations . MAIN OUTCOME MEASURES Clinical ly diagnosed AD and change in global and specific measures of cognitive function . RESULTS Diabetes mellitus was present in 127 ( 15.4 % ) of the participants . During a mean of 5.5 years of observation , 151 persons developed AD . In a proportional hazards model adjusted for age , sex , and educational level , those with diabetes mellitus had a 65 % increase in the risk of developing AD compared with those without diabetes mellitus ( hazard ratio , 1.65 ; 95 % confidence interval , 1.10 - 2.47 ) . In r and om effects models , diabetes mellitus was associated with lower levels of global cognition , episodic memory , semantic memory , working memory , and visuospatial ability at baseline . Diabetes mellitus was associated with a 44 % greater rate of decline in perceptual speed ( P = .02 ) , but not in other cognitive systems . CONCLUSIONS Diabetes mellitus may be associated with an increased risk of developing AD and may affect cognitive systems differentially Objective To investigate whether plasma interleukin-6 ( IL-6 ) is cross-sectionally related to poorer cognitive function and whether a baseline plasma IL-6 measurement can predict risk for decline in cognitive function in longitudinal follow-up of a population -based sample of nondisabled elderly people . Methods A prospect i ve cohort study of 779 high-functioning men and women aged 70 to 79 from the MacArthur Study of Successful Aging was conducted . Regression modeling was used to investigate whether baseline IL-6 levels ( classified by tertiles ) were associated with initial cognitive function and whether IL-6 levels predicted subsequent declines in cognitive function from 1988 to 1991 ( 2.5-year follow-up ) and from 1988 to 1995 ( 7-year follow-up ) . Results Subjects in the highest tertile for plasma IL-6 were marginally more likely to exhibit poorer baseline cognitive function ( i.e. , scores below the median ) , independent of demographic status , social status , health and health behaviors , and other physiologic variables ( odds ratio [ OR ] = 1.46 ; 95 % CI : 0.97 , 2.20 ) . At 2.5 years , those in both the second tertile of IL-6 ( OR = 2.21 ; 95 % CI : 1.44 , 3.42 ) and the third tertile ( OR = 2.03 ; 95 % CI : 1.30 , 3.19 ) were at increased risk of cognitive decline even after adjusting for all confounders . At 7 years of follow-up , only those in the highest IL-6 tertile were significantly more likely to exhibit declines in cognition ( OR = 1.90 ; 95 % CI : 1.14 , 3.18 ) after adjustment for all confounders . Conclusions The results suggest a relationship between elevated baseline plasma IL-6 and risk for subsequent decline in cognitive function . These findings are consistent with the hypothesized relationship between brain inflammation , as measured here by elevated plasma IL-6 , and neuropathologic disorders Background : Moderate alcohol drinking is suggested to be beneficial for cognitive functions , but the results of previous studies have varied greatly . Little is known about the effects of midlife alcohol drinking on the cognitive functions later in life . Methods : Participants were derived from r and om , population -based sample s studied in Eastern Finl and in 1972 , 1977 , 1982 , or 1987 . A total of 1,341 participants were reexamined in 1998 , after an average follow-up period of 21 years , at ages 65–79 years . Results : The participants who did not drink alcohol at midlife had a poorer performance in episodic memory , psychomotor speed , and executive function in late life as compared with infrequent and frequent drinkers , adjusted for sociodemographic and vascular factors . Also late-life nondrinkers had poorer psychomotor speed and executive function . These findings were evident especially among nonsmokers . Further , no interactions between apolipoprotein E4 and alcohol or sex and alcohol were found . Conclusions : Alcohol drinking both at midlife and later is favorably related to the function in several cognitive domains , including episodic memory , psychomotor speed , and executive function , in late life . However , it is not clear whether the association is causal , what is the possible mechanism , and what would be a safe limit of drinking for the best cognitive function Although many studies have found a cross-sectional relation between depression and dementia or depressive symptomatology and cognitive functioning , the direction of the association is still unknown . The purpose of this analysis was to determine whether high depressive symptomatology is predictive of cognitive deterioration among the elderly 3 years later . Data came from a community-based prospect i ve cohort study of noninstitutionalized and nondemented subjects aged 65 years and over living in the Gironde department in southwest France ( 1,600 subjects were interviewed at both study entry in 1989 and 3-year follow-up ) . Cognitive functions were assessed with the Mini-Mental State Examination ( MMSE ) , and cognitive deterioration was defined as an MMSE score decrease of at least five points between two assessment s. The Center for Epidemiologic Studies Depression ( CES-D ) Scale was used to evaluate the level of depressive symptomatology . The present study reports that a high level of depressive symptomatology is not predictive of cognitive deterioration 3 years later ( relative risk = 0.8 , 95 % confidence interval 0.3 - 2.1 ) . The authors observed that the risk of cognitive deterioration was associated with the concomitant level of depressive symptomatology at the 3-year follow-up , independent of depressive symptoms at entry . These results indicate that the association between high depressive symptomatology and poor cognitive functioning is cross-sectional , and they illustrate the importance of adjusting for depressive symptomatology in epidemiologic studies assessing cognitive functions Studies of disability in old age have focused on gross measures of physical functioning Output:	The meta- analysis shows a moderate association between obesity and the risks for dementia and AD .

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