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MS21800	*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 objective of this study was to compare the relative effectiveness of two modes of delivering Behavioral Family Systems Therapy for Diabetes ( BFST-D ) to improve adherence and glycemic control among adolescents with type 1 diabetes with suboptimal glycemic control ( HbA1c ≥9.0 % [ ≥74.9 mmol/mol ] ) : face to face in clinic ( Clinic ) and Internet videoconferencing ( Skype ) conditions . RESEARCH DESIGN AND METHODS Adolescents aged 12 to 18 years and at least one adult caregiver were r and omized to receive BFST-D via the Clinic or Skype condition . Participants completed up to 10 therapy sessions within a 12-week period . Changes in youth- and parent-reported adherence and glycemic control were compared before and after the intervention and at follow-up assessment . RESULTS Using an intent-to-treat analytic approach , no significant between-group differences were identified between the before , after , and follow-up assessment s. Groups were collapsed to examine the overall effects of BFST-D on adherence and glycemic control . Results identified that statistically significant improvements in adherence and glycemic control occurred from before to after the intervention ; improvements were maintained at 3-month follow-up . CONCLUSIONS Delivery of BFST-D via Internet-based videoconferencing is viable for addressing nonadherence and suboptimal glycemic control in adolescents with type 1 diabetes , potentially reducing important barriers to care for youth and families The purpose of this report is to summarize and integrate the findings of the Diabetes Control and Complications Trial ( DCCT ) , a r and omized controlled clinical trial , and the succeeding observational follow-up of the DCCT cohort in the Epidemiology of Diabetes Interventions and Complications ( EDIC ) study , regarding the effects of intensive treatment on the microvascular complications of type 1 diabetes mellitus . The DCCT proved that intensive treatment reduced the risks of retinopathy , nephropathy , and neuropathy by 35 % to 90 % compared with conventional treatment . The absolute risks of retinopathy and nephropathy were proportional to the mean glycosylated hemoglobin ( HbA(1c ) ) level over the follow-up period preceding each event . Intensive treatment was most effective when begun early , before complications were detectable . These risk reductions , achieved at a median HbA(1c ) level difference of 9.1 % for conventional treatment vs 7.3 % for intensive treatment have been maintained through 7 years of EDIC , even though the difference in mean HbA(1c ) levels of the 2 former r and omized treatment groups was only 0.4 % at 1 year ( P<.001 ) ( 8.3 % in the former conventional treatment group vs 7.9 % in the former intensive treatment group ) , continued to narrow , and became statistically nonsignificant by 5 years ( 8.1 % vs 8.2 % , P = .09 ) . The further rate of progression of complications from their levels at the end of the DCCT remains less in the former intensive treatment group . Thus , the benefits of 6.5 years of intensive treatment extend well beyond the period of its most intensive implementation . Intensive treatment should be started as soon as is safely possible after the onset of type 1 diabetes mellitus and maintained thereafter , aim ing for a practicable target HbA(1c ) level of 7.0 % or less OBJECTIVE Widespread use of carbohydrate counting is limited by its complex education . In this study we compared a Diabetes Interactive Diary ( DID ) with st and ard carbohydrate counting in terms of metabolic and weight control , time required for education , quality of life , and treatment satisfaction . RESEARCH DESIGN AND METHODS Adults with type 1 diabetes were r and omly assigned to DID ( group A , n = 67 ) or st and ard education ( group B , n = 63 ) and followed for 6 months . A subgroup also completed the SF-36 Health Survey ( SF-36 ) and World Health Organization-Diabetes Treatment Satisfaction Question naire ( WHO-DTSQ ) at each visit . RESULTS Of 130 patients ( aged 35.7 ± 9.4 years ; diabetes duration 16.5 ± 10.5 years ) , 11 dropped out . Time for education was 6 h ( range 2–15 h ) in group A and 12 h ( 2.5–25 h ) in group B ( P = 0.07 ) . A1C reduction was similar in both groups ( group A from 8.2 ± 0.8 to 7.8 ± 0.8 % and group B from 8.4 ± 0.7 to 7.9 ± 1.1 % ; P = 0.68 ) . Nonsignificant differences in favor of group A were documented for fasting blood glucose and body weight . No severe hypoglycemic episode occurred . WHO-DTSQ scores increased significantly more in group A ( from 26.7 ± 4.4 to 30.3 ± 4.5 ) than in group B ( from 27.5 ± 4.8 to 28.6 ± 5.1 ) ( P = 0.04 ) . Role Physical , General Health , Vitality , and Role Emotional SF-36 scores improved significantly more in group A than in group B. CONCLUSIONS DID is at least as effective as traditional carbohydrate counting education , allowing dietary freedom for a larger proportion of type 1 diabetic patients . DID is safe , requires less time for education , and is associated with lower weight gain . DID significantly improved treatment satisfaction and several quality -of-life dimensions OBJECTIVE To conduct a 1-year r and omized clinical trial to evaluate a remote comprehensive diabetes self-management education ( DSME ) intervention , Diabetes TeleCare , administered by a dietitian and nurse/certified diabetes educator ( CDE ) in the setting of a federally qualified health center ( FQHC ) in rural South Carolina . RESEARCH DESIGN AND METHODS Participants were recruited from three member health centers of an FQHC and were r and omized to either Diabetes TeleCare , a 12-month , 13-session curriculum delivered using telehealth strategies , or usual care . RESULTS Mixed linear regression model results for repeated measures showed a significant reduction in glycated hemoglobin ( GHb ) in the Diabetes TeleCare group from baseline to 6 and 12 months ( 9.4 ± 0.3 , 8.3 ± 0.3 , and 8.2 ± 0.4 , respectively ) compared with usual care ( 8.8 ± 0.3 , 8.6 ± 0.3 , and 8.6 ± 0.3 , respectively ) . LDL cholesterol was reduced at 12 months in the Diabetes TeleCare group compared with usual care . Although not part of the original study design , GHb was reduced from baseline to 12 and 24 months in the Diabetes TeleCare group ( 9.2 ± 0.4 , 7.4 ± 0.5 , and 7.6 ± 0.5 , respectively ) compared with usual care ( 8.7 ± 0.4 , 8.1 ± 0.4 , and 8.1 ± 0.5 , respectively ) in a post hoc analysis of a subset of the r and omized sample who completed a 24-month follow-up visit . CONCLUSIONS Telehealth effectively created access to successfully conduct a 1-year remote DSME by a nurse CDE and dietitian that improved metabolic control and reduced cardiovascular risk in an ethnically diverse and rural population The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement is used worldwide to improve the reporting of r and omized , controlled trials . Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . BACKGROUND The objective was to compare glycemic control between prepr and ial and postpr and ial bolus administration ( 15 min before [ PRE ] or immediately after the meal [ POST ] ) in patients with type 1 diabetes using insulin pump and real-time continuous glucose monitoring . METHODS Between September 2015 and February 2016 , a single-centre , open r and omized , 2-way crossover study of patients on bolus insulin aspart administration was conducted during two 14-day periods and according to 2 administration regimen schedules ( PRE/POST or POST/PRE ) . Inclusion criteria were as follows : patients with type 1 diabetes , ≥18 and ≤ 65 years old , treated with insulin aspart using a Medtronic ® insulin pump and trained on functional insulin therapy . Patients were r and omly assigned to either regimen schedule . At the beginning of each period , each patient was provided with a st and ardized high fat meal . Primary outcome was the area under the curve for interstitial glucose above 140 mg/dL per minute ( AUC > 140 mg/dL/min ) during each period . Secondary outcomes were time spent in hypo/eu/hyperglycemia , glycemic variability indices , and AUC during 4 hours after high fat meal calculated with continuous glucose monitoring data . RESULTS Twenty-two patients were included . Mean AUC > 140 mg/dL/min was statistically higher in patients on POST ( 43.70 mg/dL/min ; 95%CI : 34.08 to 53.31 ) versus PRE insulin aspart regimen ( 37.24 mg/dL/min 95%CI : 27.63 to 46.85 ) ( P = 0.03 ) . Mean interstitial glycemia and glycemic variability indices were also increased ( P < 0.05 ) on POST regimen . The mean AUC 4 hours after the high fat meal was higher on POST regimen but not statistically different ( P = 0.06 ) . CONCLUSIONS In our study , postpr and ial administration of insulin aspart appears to mildly increase glycemic excursion and glycemic variability OBJECTIVE To report results from YourWay , an Internet-based self-management intervention for adolescents with type 1 diabetes . RESEARCH DESIGN AND METHODS A total of 72 adolescents with type 1 diabetes , ages 13–17 years , were r and omized to a usual-care-plus-Internet support or a usual-care group . The intervention was design ed to enhance problem-solving barriers to self-management . A1C was obtained from medical records , and problem-solving and self-management were obtained via adolescent report . RESULTS Group differences were not statistically significant using intent-to-treat analyses . Using as-treated analyses , adolescents in the treatment condition showed statistically significant improvement in self-management ( d = 0.64 ; P = 0.02 ) and important improvements in problem-solving ( d = 0.30 ; P = 0.23 ) and A1C ( d = −0.28 ; P = 0.27 ) . Mean A1C for the intervention group remained constant ( −0.01 % ) , while the control group increased ( 0.33 % ) . CONCLUSIONS This brief trial suggests that self-management support delivered through a secure website may improve self-management and offset typical decreases in adolescent glycemic control OBJECTIVE DAFNE ( Dose Adjustment For Normal Eating ) , a structured education program in flexible insulin therapy , has been widely adopted in the U.K. after validation in a r and omized trial . To determine benefits in routine practice , we collected biomedical and psychological data from all participants attending during a 12-month period . RESEARCH DESIGN AND METHODS HbA1c , weight , self-reported hypoglycemia awareness , severe hypoglycemia frequency , PAID ( Problem Areas In Diabetes ) , HADS ( Hospital Anxiety and Depression Scale ) , and EuroQol Group 5-Dimension Self-Report Question naire scores were recorded prior to DAFNE and after 1 year . RESULTS Complete baseline and follow-up HbA1c data were available for 639 ( 54.9 % ) of 1,163 attendees . HbA1c fell from 8.51 ± 1.41 ( mean ± SD ) to 8.24 ± 1.29 % ( difference 0.27 [ 95 % CI 0.16–0.38 ] ; P < 0.001 ) , with a greater mean fall of 0.44 % from baseline HbA1c > 8.5 % . Severe hypoglycemia rate fell from 1.7 ± 8.5 to 0.6 ± 3.7 episodes per person per year ( 1.1 [ 0.7–1.4 ] ) and hypoglycemia recognition improved in 43 % of those reporting unawareness . Baseline psychological distress was evident , with a PAID score of 25.2 and HADS scores of 5.3 ( anxiety ) and 4.8 ( depression ) , falling to 16.7 ( 8.5 [ 6.6–10.4 ] ) , 4.6 ( 0.7 [ 0.4–1.0 ] ) , and 4.2 ( 0.6 [ 0.3–0.8 ] ) , respectively ( all P < 0.001 at 1 year ) . Clinical ly relevant anxiety and depression ( HADS ≥8 ) fell Output:	The effect of e-health educational interventions on HbA1c in patients with T1D is comparable to the st and ard care .
MS21801	*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 previous clinical study , a probiotic formulation ( PF ) consisting of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 ( PF ) decreased stress-induced gastrointestinal discomfort . Emerging evidence of a role for gut microbiota on central nervous system functions therefore suggests that oral intake of probiotics may have beneficial consequences on mood and psychological distress . The aim of the present study was to investigate the anxiolytic-like activity of PF in rats , and its possible effects on anxiety , depression , stress and coping strategies in healthy human volunteers . In the pre clinical study , rats were daily administered PF for 2 weeks and subsequently tested in the conditioned defensive burying test , a screening model for anti-anxiety agents . In the clinical trial , volunteers participated in a double-blind , placebo-controlled , r and omised parallel group study with PF administered for 30 d and assessed with the Hopkins Symptom Checklist ( HSCL-90 ) , the Hospital Anxiety and Depression Scale ( HADS ) , the Perceived Stress Scale , the Coping Checklist ( CCL ) and 24 h urinary free cortisol ( UFC ) . Daily subchronic administration of PF significantly reduced anxiety-like behaviour in rats ( P < 0·05 ) and alleviated psychological distress in volunteers , as measured particularly by the HSCL-90 scale ( global severity index , P < 0·05 ; somatisation , P < 0·05 ; depression , P < 0·05 ; and anger-hostility , P < 0·05 ) , the HADS ( HADS global score , P < 0·05 ; and HADS-anxiety , P < 0·06 ) , and by the CCL ( problem solving , P < 0·05 ) and the UFC level ( P < 0·05 ) . L. helveticus R0052 and B. longum R0175 taken in combination display anxiolytic-like activity in rats and beneficial psychological effects in healthy human volunteers Indigenous lactic acid fermented foods may have potential as probiotic treatment for diarrhoea , due to high levels of lactic acid bacteria . In this study the effect of a millet drink , spontaneously fermented by lactic acid bacteria , as a therapeutic agent among Ghanaian children with diarrhoea , was assessed . Children below 5 years of age coming to Northern Ghana health clinics for treatment of diarrhoea were r and omised to two groups . Children of both groups received treatment for diarrhoea given at the local clinic . The intervention group in addition received up to 300 ml fermented millet drink ( KSW ) daily for 5 days after enrolment . The clinical outcome of diarrhoea and reported well-being were registered every day for the 5-day intervention and again 14 days after diagnosis . Among 184 children ( mean age 17.4 , st and ard deviation 11.3 months ) included , no effects of the intervention were found with respect to stool frequency , stool consistency and duration of diarrhoea . However , KSW was associated with greater reported well-being 14 days after the start of the intervention ( P=0.02 ) . The fact that no effect of KSW on diarrhoea was observed could be because many children had a mild form of diarrhoea , and many were treated with antibiotics . Either this could have affected the lactic acid bacteria , or the lactic acid bacteria in KSW had no probiotic effects . It is speculated that the effect after two weeks could be due to a preventing effect of KSW on antibiotic-associated diarrhoea which could help reducing persistent diarrhoea Probiotics are live microorganisms that exert beneficial effects on the host , when administered in adequate amounts . Mostly , probiotics affect the gastrointestinal ( GI ) tract of the host and alter the composition of gut microbiota . Nowadays , the incidence of hip fractures due to osteoporosis is increasing worldwide . Ovariectomized ( OVX ) rats have fragile bone due to estrogen deficiency and mimic the menopausal conditions in women . Therefore , this study aim ed to examine the effects of Bifidobacterium longum ( B. longum ) on bone mass density ( BMD ) , bone mineral content ( BMC ) , bone remodeling , bone structure , and gene expression in OVX rats . The rats were r and omly assigned into 3 groups ( sham , OVX , and the OVX group supplemented with 1 mL of B. longum 108–109 colony forming units (CFU)/mL ) . B. longum was given once daily for 16 weeks , starting from 2 weeks after the surgery . The B. longum supplementation increased ( p < 0.05 ) serum osteocalcin ( OC ) and osteoblasts , bone formation parameters , and decreased serum C-terminal telopeptide ( CTX ) and osteoclasts , bone resorption parameters . It also altered the microstructure of the femur . Consequently , it increased BMD by increasing ( p < 0.05 ) the expression of Sparc and Bmp-2 genes . B. longum alleviated bone loss in OVX rats and enhanced BMD by decreasing bone resorption and increasing bone formation Output:	Studies from some African countries suggest that fermented foods of probiotics relevance have effectively shown metal chelation properties . Consumption of Nigerian fermented foods may hold a promise in checking the high body burden of heavy metals in Nigeria .
MS21802	*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: Experimental challenge studies may generate and test hypotheses regarding the pathophysiology of panic disorder and may serve to identify pathophysiologically relevant subtypes . It has been suggested that gender-related differences may be relevant in the development and maintenance of panic disorder . In a r and omized double blind design the effects of placebo and sodium lactate administration in 14 female and 16 male patients with panic disorder and 23 healthy control subjects were compared using the Acute Panic Inventory ( API ) score and derived formal criteria for a panic attack . Panic attack frequency following sodium lactate was 76.6 % in the patient group . Although control subjects had a lactate-induced increase in the API score as well , this effect was much weaker . No panic attacks occurred in patients with panic disorder or healthy control subjects receiving a placebo . However , a gender effect was observed in the putative panicogenic placebo condition : female patients with panic disorder had more subthreshold panic anxiety as measured with the API score . The data give evidence for an increased nocebo response in female patients with panic disorder Nocebo hyperalgesia has received sparse experimental attention compared to placebo analgesia . The aim of the present study was to investigate if personality traits and fear of pain could predict experimental nocebo hyperalgesia . One hundred and eleven healthy volunteers ( 76 females ) participated in an experimental study in which personality traits and fear of pain were measured prior to induction of thermal heat pain . Personality traits were measured by the Big-Five Inventory-10 . Fear of pain was measured by the Fear of Pain Question naire III . Heat pain was induced by a PC-controlled thermode . Pain was measured by a computerized visual analog scale . Stress levels during the experiment were measured by numerical rating scales . The participants were r and omized to a Nocebo group or to a no-treatment Natural History group . The results revealed that pain and stress levels were significantly higher in the Nocebo group after nocebo treatment . Mediation analysis showed that higher levels of the Fear of Pain Question naire III factor “ fear of medical pain ” significantly increased stress levels after nocebo treatment and that higher stress levels were associated with increased nocebo hyperalgesic responses . There were no significant associations between any of the personality factors and the nocebo hyperalgesic effect . The results from the present study suggest that dispositional fear of pain might be a useful predictor for nocebo hyperalgesia and emotional states concomitant with expectations of increased pain . Furthermore , measurement of traits that are specific to pain experience is probably better suited for prediction of nocebo hyperalgesic responses compared to broad measures of personality OBJECTIVE This study investigated the impact of the social modeling of side effects following placebo medication ingestion on the nocebo and placebo effect . It also investigated whether medication br and ing ( br and or generic labeling ) moderated social modeling effects . METHOD Eighty-two university students took part in the study which was purportedly investigating the impact of fast-acting beta-blocker medications ( actually placebos ) on preexamination anxiety . After taking the medication , participants were r and omized to either witness a female confederate report experiencing side effects or no side effects after taking the same medication . Differences in symptom reporting , blood pressure , heart rate , and anxiety were assessed between the social modeling of side effects and no modeling groups . RESULTS Seeing a female confederate report side effects reduced the placebo effect in systolic ( p = .009 ) and diastolic blood pressure ( p = .033 ) . Seeing a female confederate report side effects also increased both total reported symptoms ( mean [ SE ] 7.35 [ .54 ] vs. 5.16 [ 0.53 ] p = .005 ) and symptoms attributed to the medication ( 5.27 [ 0.60 ] vs. 3.04 [ 0.59 ] p = .01 ) , although the effect on symptoms was only seen in female participants . Females who saw the confederate report side effects reported approximately twice the number of symptoms as those in the no modeling group . Social modeling did not affect heart rate or anxiety . Medication br and ing did not influence placebo or nocebo outcomes . CONCLUSIONS The social modeling of symptoms can substantially reduce or eliminate the placebo effect . Viewing a female confederate display symptoms after taking the same medication increases symptom reporting in females UNLABELLED Expectations and beliefs shape the experience of pain . This is most evident in context -induced , placebo analgesia , which has recently been shown to interact with the trait of magical thinking ( MT ) in adults . In children , placebo analgesia and the possible roles that MT and gender might play as modulators of placebo analgesia have remained unexplored . Using a paradigm in which heat pain stimuli were applied to both forearms , we investigated whether MT and gender can influence the magnitude of placebo analgesia in children . Participants were 49 right-h and ed children ( aged 6 - 9 years ) who were r and omly assigned-stratified for MT and gender-to either an analgesia-expectation or a control-expectation condition . For both conditions , the placebo was a blue-colored h and disinfectant that was applied to the children 's forearms . Independent of MT , the placebo treatment significantly increased both heat pain threshold and tolerance . The threshold placebo effect was more pronounced for girls than boys . In addition , independent of the expectation treatment , low-MT boys showed a lower tolerance increase on the left compared to the right side . Finally , MT specifically modulated tolerance on the right forearm side : Low-MT boys showed an increase , whereas high-MT boys showed a decrease in heat pain tolerance . This study documented a substantial expectation-induced placebo analgesia response in children ( girls > boys ) and demonstrated MT and gender-dependent laterality effects in pain perception . The findings may help improve individualized pain management for children . PERSPECTIVE The study documents the first experimental evidence for a substantial expectancy-induced placebo analgesia response in healthy children aged 6 to 9 years ( girls > boys ) . Moreover , the effect was substantially higher than the placebo response typically found in adults . The findings may help improve individualized pain management for children Background : Expectancy and modeling have been cited as factors in mass psychogenic illness ( MPI ) , which reportedly affects more women than men . Purpose : The purpose of the study is to assess the effects of expectancy and modeling in a controlled laboratory analogue of MPI . Methods : Students were r and omly assigned to inhale or not inhale an inert placebo described as a suspected environmental toxin that had been linked to four symptoms typical of reported instances of MPI . Half of the students observed a female confederate inhale the substance and subsequently display the specified symptoms . Results : Students who inhaled the placebo reported greater increases in symptoms , and the increase was significantly greater for the specified symptoms than for other symptoms . Observation of the confederate displaying symptoms increased specified symptoms significantly among women but not among men . Changes in reported symptoms were significantly associated with changes in unobtrusively observed behavior . Conclusions : Symptoms typical of clinical reports of MPI can be induced by manipulating response expectancies , and the effects are specific rather than generalized . Among women , this effect is enhanced by observing another participant ( who in this study is also female ) display symptoms . This suggests that the preponderance of women showing symptoms in outbreaks of MPI may be due to gender-linked differences in the effects of modeling on psychogenic symptoms We conjectured that individual differences in tension-reduction alcohol outcome expectancies ( TR-AOEs ) could produce widely varying responses to manipulations in alcohol-placebo studies and tested this idea by having individuals with social phobia give speeches in front of a group . One speech occurred before and one after participants consumed either a placebo beverage or a control beverage ( i.e. , a nonalcoholic drink described as containing no alcohol ) . Study results indicate that the placebo manipulation reduced cognitive and affective symptoms of anxiety to a greater extent for males with high TR-AOEs than for males with low TR-AOEs . This pattern was not found for women in the placebo group or for individuals in the control group . These findings demonstrate a moderating effect of TR-AOEs on the association between the consumption of a placebo beverage and response to an anxiety challenge and highlight the importance of accounting for gender and outcome expectancies when evaluating psychoactive substances Rationale In a r and omised placebo-controlled clinical trial it is assumed that psychosocial effects of the treatment , regression to the mean and spontaneous remission are identical in the drug and placebo group . Consequently , any difference between the groups can be ascribed to the pharmacological effects . Previous studies suggest that side effects of drugs can enhance expectancies of treatment effects in the drug group compared to the placebo group , and thereby increase placebo responses in the drug group compared to the placebo group . Objectives The hypothesis that side effects of drugs can enhance expectancies and placebo responses was tested . Method Painful laser stimuli were delivered to 20 healthy subjects before and after administration of a drink with 0 or 4 mg/kg caffeine . The drink was administered either with information that it contained a painkiller or that it was a placebo . Laser-evoked potentials and reports of pain , expectancy , arousal and stress were measured . Results Four milligrammes per kilogramme of caffeine reduced pain . Information that a painkiller was administered increased the analgesic effect of caffeine compared to caffeine administered with no drug information . This effect was mediated by expectancies . Information and expectancies had no effect on pain intensity when 0 mg/kg was administered . Conclusion The analgesic effect of caffeine was increased by information that a painkiller was administered . This was due to an interaction of the pharmacological action of the drug and expectancies . Hence , psychosocial effects accompanying a treatment can differ when an active drug is administered compared to a placebo The nocebo effect is the onset of untoward reactions following the administration of an indifferent substance . The oral challenge with alternative drugs plays a central role in the management of drug allergy and the use of inert substances is part of this procedure . We evaluated the occurrence and clinical characteristics of nocebo effect in patients with adverse drug reactions . Six hundred patients , seen in three different centres ( Genoa , Naples and Verona ) with a history of reactions to drugs , underwent a blind oral challenge with the administration of an indifferent substance and active drugs . The administration of an inert substance provoked untoward reactions in 54 patients ( 27 % ) in Verona , 60 ( 30 % ) in Naples and 48 ( 24 % ) in Genoa . The overall occurrence of nocebo effect was 27 % . The majority of reactions were subjective symptoms ( itching , malaise , headache etc ) , perceived as troublesome by all subjects . The occurrence was significantly higher in women than in men . Our data , collected in a large population , confirm that the nocebo effect occurs frequently in clinical practice . In managing adverse drug reactions through oral challenge the nocebo effect is m and atory to recognize false positive responses BACKGROUND Social cues and interpersonal interactions strongly contribute to evoke placebo effects that are pervasive in medicine and depend upon the activation of endogenous modulatory systems . Here , we explore the possibility to boost placebo effects by targeting pharmacologically the vasopressin system , characterized by a sexually dimorphic response and involved in the regulation of human and nonhuman social behaviors . METHODS We enrolled 109 healthy participants and studied the effects of intranasal administration of an arginine vasopressin 1A and 1B receptor agonist against 1 ) no treatment , 2 ) oxytocin , and 3 ) saline in a r and omized , placebo-controlled , double-blind , parallel design trial using a well-established model of placebo analgesia while controlling for sex differences . RESULTS Vasopressin agonists boosted placebo effects in women but had no effect in men . The effects of vasopressin on expectancy-induced analgesia were significantly larger than those observed in the no-treatment ( p < .004 ) , oxytocin ( p < .001 ) , and saline ( p < .015 ) groups . Moreover , women with lower dispositional anxiety and cortisol levels showed the largest vasopressin-induced modulation of placebo effects , suggesting a moderating interplay between pre-existing psychological factors and treatment cortisol changes . CONCLUSIONS This is the first study that demonstrates that arginine vasopressin boosts placebo effects and that the effect of vasopressin depends upon a significant sex by treatment interaction . These findings are novel and might open up new avenues for clinical ly relevant research due to the therapeutic potentials of vasopressin as well as the possibility to systematic ally control for influences of placebo responses in clinical trials We investigated the mechanisms underlying the activation of endogenous opioids in placebo analgesia by using the model of human experimental ischemic arm pain . Different types of placebo analgesic responses were evoked by means of cognitive expectation cues , drug conditioning , or a combination of both . Drug conditioning was performed by means of either the opioid agonist morphine hydrochloride or the nonopioid ketorolac tromethamine . Expectation cues produced placebo responses that were completely blocked by the opioid antagonist naloxone . Expectation cues together with morphine conditioning produced placebo responses that were completely antagonized by naloxone . Morphine conditioning alone ( without expectation cues ) induced a naloxone-reversible placebo effect . By contrast , ketorolac conditioning together with expectation cues elicited a placebo effect that was blocked by naloxone only partially . Ketorolac conditioning alone produced placebo responses that were naloxone-insensitive . Therefore , we evoked different types of placebo responses that were either naloxone-reversible or partially naloxone-reversible or , otherwise , naloxone-insensitive , depending on the procedure used to evoke the placebo response . These findings show that cognitive factors and conditioning are balanced in different ways in placebo analgesia , and this balance is crucial for the activation Output:	This review indicates that there are sex differences in the placebo and nocebo effects , probably caused by sex differences in stress , anxiety , and the endogenous opioid system
MS21803	*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: To determine whether prenatal corticosteroid therapy would reduce the incidence of neonatal necrotizing enterocolitis ( NEC ) , we assigned a total of 466 women admitted in premature labor either to receive placebo ( group A , n = 256 ) , if delivery was expected to occur within 24 hours of admission , or to receive betamethasone ( group B , n = 210 ) if delivery was expected to take place more than 24 hours after admission . All women were free of severe medical complications or drug therapy ; cases of intrauterine growth retardation or premature rupture of the membranes were excluded . Their newborn infants , excluding malformed , congenitally infected , and growth-retarded infants , were enrolled in the study unless they had died before the age of 10 postnatal days . Babies born to group A mothers ( n = 248 ) were further assigned to a treatment group ( group A1 , n = 130 ) receiving dexamethasone , 2 mg/kg/day by intravenous injection during the first 7 days of life , or to a control group ( group A2 , n = 118 ) receiving 10 % dextrose solution placebo . Group B infants ( prenatal betamethasone , n = 205 ) received neither treatment nor placebo . The incidence of NEC in group A1 was 6.9 % ( 9/130 ) , and in group A2 it was 14.4 % ( 17/118 ) ( p less than 0.05 ) . In group B the incidence was 3.4 % ( 7/205 ) ; this was much lower than in group A2 ( p less than 0.01 ) and lower than in group A combined ( 10.4 % ) ( p less than 0.01 ) . There was no death from NEC and no surgical intervention among group B patients . The mortality rate for group A1 ( 11 % ) was lower than for group A2 ( 56 % ) ( p less than 0.02 ) . There were fewer indications for surgical intervention for NEC in group A1 than in group A2 . Histologic studies confirmed bowel ischemia in all specimens analyzed . These data support the hypothesis that the incidence of NEC is significantly reduced after prenatal steroid treatment . Although postnatal therapy with steroids does not decrease the incidence as effectively as prenatal therapy , it improves clinical outcome of NEC Early postnatal use of dexamethasone has recently been shown to be effective in improving the pulmonary status in premature infants with respiratory distress syndrome ( RDS ) . To study the effect of dexamethasone on pulmonary inflammatory responses , we studied ten infants treated with dexamethasone and ten infants without this treatment . Serial tracheal aspirates were obtained for cell counts , neutrophil counts , total protein concentrations , and leukotriene B4 ( LTB4 ) and 6-keto prostagl and in (PG)F(1 alpha ) levels before and after starting the study . Infants in the dexamethasone-treated group required significantly lower mean airway pressures for ventilation and had lower PaCO2 values from day 3 to day 14 than infants in the control group , suggesting better pulmonary function . For infants in the dexamethasone group , the tracheal aspirates showed significantly lower cell and neutrophil counts , protein concentrations , and 6-keto-PGF(1 alpha ) and LTB4 levels than in the control group . We conclude that early postnatal dexamethasone therapy may lessen lung inflammation and improve pulmonary function in infants with RDS Dexamethasone was compared with placebo in a double-blind , crossover , r and omised study of infants with severe bronchopulmonary dysplasia who had required mechanical ventilation for at least four weeks , despite treatment with diuretics , methylxanthines , bronchodilators , fluid restriction , nutritional supplementation , and ligation of the patent ductus arteriosus when indicated . Gestational age ranged from 27 to 33 weeks and birth weight from 800 to 1730 g. Patients received dexamethasone ( 0 . 5 mg/kg/day ) or normal saline for the first 3 days , then treatment was crossed over for the next 3 days . The study was terminated when sequential analysis showed that all six patients had improved during dexamethasone therapy . Significant improvements were seen in ventilator-determined respiratory rate , peak inspiratory pressure , fractional inspired oxygen concentration , and alveolar arterial oxygen gradients ( p less than 0 . 05 ) . Although dexamethasone hastened weaning from mechanical ventilation , infection occurred in a substantial proportion of patients Background . Although several trials of early dexamethasone therapy have been completed to determine if such therapy would reduce mortality and chronic lung disease ( CLD ) in infants with respiratory distress , optimal duration and side effects of such therapy remain unknown . Purpose . The purpose of this study was : 1 ) to determine if a 3-day course of early dexamethasone therapy would reduce CLD and increase survival without CLD in neonates who received surfactant therapy for respiratory distress syndrome and 2 ) to determine adverse effects associated with such therapy . Design . This was a prospect i ve multicenter r and omized trial comparing a 3-day course of dexamethasone therapy beginning at 24 to 48 hours of life to placebo therapy . Two hundred forty-one neonates ( dexamethasone n = 118 , placebon = 123 ) , who weighed between 500 g and 1500 g , received surfactant therapy , and were at significant risk for CLD or death using a model to predict CLD or death at 24 hours of life , were enrolled in the trial . Infants r and omized to receive early dexamethasone were given 6 doses of dexamethasone at 12-hour intervals beginning at 24 to 48 hours of life . The primary outcomes compared were survival without CLD and CLD . CLD was defined by the need for supplemental oxygen at the gestational age of 36 weeks . Complication rates and adverse effects of study drug therapy were also compared . Results . Neonates r and omized to early dexamethasone treatment were more likely to survive without CLD ( RR : 1.3 ; 95 % CI : 1.03 , 1.7 ) and were less likely to develop CLD ( RR : 0.6 ; CI : 0.3 , 0.98 ) . Mortality rates were not significantly different . Subsequent dexamethasone therapy use was less in early dexamethasone-treated neonates ( RR : 0.8 ; CI : 0.7 , 0.96 ) . Very early ( ≤7 days of life ) intestinal perforations were more common among dexamethasone-treated neonates ( 8 % vs 1 % ) . Conclusion . We conclude that an early 3-day course of dexamethasone therapy increases survival without CLD , reduces CLD , and reduces late dexamethasone therapy in high-risk , low birth weight infants who receive surfactant therapy for respiratory distress syndrome . Potential benefits of early dexamethasone therapy at the dosing schedule used in this trial need to be weighed against the risk for early intestinal perforation Background : Dexamethasone treatment is associated with an increased risk of cerebral palsy ( CP ) . Early hydrocortisone ( HC ) treatment may decrease the incidence of bronchopulmonary dysplasia ; however , the long-term effects are still under evaluation . Follow-up of r and omized studies concerning early HC treatment is essential to confirm the long-term safety . Objective : We hypothesized that early HC treatment in very preterm infants does not impair the neurologic outcome . Methods : We report follow-up data from a r and omized trial of early HC given for 10 days . Before the HC or placebo treatment , serum cortisol levels were measured . Receiver-operating characteristic was defined . Values below the median were classified as low endogenous cortisol and those above the median as high endogenous cortisol . A meta- analysis was performed . Results : Altogether 98 % of the 46 surviving infants participated in a follow-up study at a corrected age of 2 years . The growth characteristics were similar between the study groups . The developmental quotients ( DQs ) of the children with high endogenous cortisol and placebo treatment shortly after birth ( 100 ± 13 ) and those with low endogenous cortisol and HC ( 97 ± 7 ) were not lower than the DQs of the children with high endogenous cortisol and HC ( 92 ± 3 ) or low cortisol and placebo ( 96 ± 2 ) . According to a meta- analysis of three available trials ( 411 children ) , the rate of CP and survival without neurosensory or cognitive impairment was not influenced by HC . Conclusion : Early low-dose HC administration had no adverse effects at 2 years of age . Further studies are required to define the target group for neonatal HC BACKGROUND . Low cortisol concentrations in premature infants have been correlated with increased severity of illness , hypotension , mortality , and development of bronchopulmonary dysplasia . A total of 360 mechanically ventilated infants with a birth weight of 500 to 999 g were enrolled in a r and omized , multicenter trial of prophylaxis of early adrenal insufficiency to prevent bronchopulmonary dysplasia . Mortality and bronchopulmonary dysplasia were decreased in the hydrocortisone-treated patients exposed to chorioamnionitis . We now report outcomes at 18 to 22 months ' corrected age . PATIENTS AND METHODS . Surviving infants were evaluated with st and ardized neurologic examination and Bayley Scales of Infant Development-II . Neurodevelopmental impairment was defined as a Mental Developmental Index or Psychomotor Developmental Index of < 70 , cerebral palsy , blindness or deafness . RESULTS . A total of 252 ( 87 % ) of 291 survivors were evaluated . Cerebral palsy was diagnosed in 13 % of hydrocortisone-treated versus 14 % of placebo-treated infants . Fewer hydrocortisone-treated infants had a Mental Development Index < 70 , and more of the hydrocortisone-treated infants showed evidence of awareness of object permanence . Incidence of neurodevelopmental impairment was not different ( 39 % [ hydrocortisone ] vs 44 % [ placebo ] ) . There were no differences in physical growth measures . Chorioamnionitis-exposed infants treated with hydrocortisone were shorter and weighed less than controls but had no evidence of neurodevelopmental impairment . Among infants not exposed to chorioamnionitis , hydrocortisone-treated patients were less likely to have a Mental Development Index of < 70 or to be receiving glucocorticoids at follow-up . CONCLUSIONS . Early , low-dose hydrocortisone treatment was not associated with increased cerebral palsy . Treated infants had indicators of improved developmental outcome . Together with the short-term benefit previously reported , these data support additional studies of hydrocortisone treatment of adrenal insufficiency in extremely premature infants BACKGROUND Early administration of high doses of dexamethasone may reduce the risk of chronic lung disease in premature infants but can cause complications . Whether moderate doses would be as effective but safer is not known . METHODS We r and omly assigned 220 infants with a birth weight of 501 to 1000 g who were treated with mechanical ventilation within 12 hours after birth to receive dexamethasone or placebo with either routine ventilatory support or permissive hypercapnia . The dexamethasone was administered within 24 hours after birth at a dose of 0.15 mg per kilogram of body weight per day for three days , followed by a tapering of the dose over a period of seven days . The primary outcome was death or chronic lung disease at 36 weeks ' postmenstrual age . RESULTS The relative risk of death or chronic lung disease in the dexamethasone-treated infants , as compared with those who received placebo , was 0.9 ( 95 percent confidence interval , 0.8 to 1.1 ) . Since the effect of dexamethasone treatment did not vary according to the ventilatory approach , the two dexamethasone groups and the two placebo groups were combined . The infants in the dexamethasone group were less likely than those in the placebo group to be receiving oxygen supplementation 28 days after birth ( P=0.004 ) or open-label dexamethasone ( P=0.01 ) , were more likely to have hypertension ( P<0.001 ) , and were more likely to be receiving insulin treatment for hyperglycemia ( P=0.02 ) . During the first 14 days , spontaneous gastrointestinal perforation occurred in a larger proportion of infants in the dexamethasone group ( 13 percent , vs. 4 percent in the placebo group ; P=0.02 ) . The dexamethasone-treated infants had a lower weight ( P=0.02 ) and a smaller head circumference ( P=0.04 ) at 36 weeks ' postmenstrual age . CONCLUSIONS In preterm infants , early administration of dexamethasone at a moderate dose has no effect on death or chronic lung disease and is associated with gastrointestinal perforation and decreased growth OBJECTIVES To study whether early postnatal ( < 12 hours Output:	There were significant benefits for the following outcomes : lower rates of failure to extubate and decreased risks of chronic lung disease at both 28 days and 36 weeks ' postmenstrual age , death or chronic lung disease at 28 days and 36 weeks ' postmenstrual age , patent ductus arteriosus and ROP , including severe ROP . There were no significant differences in the rates of neonatal or subsequent mortality , infection , severe intraventricular haemorrhage , periventricular leukomalacia , necrotising enterocolitis or pulmonary haemorrhage . Gastrointestinal bleeding and intestinal perforation were important adverse effects . The risks of hyperglycaemia , hypertension , hypertrophic cardiomyopathy and growth failure were also increased . In subgroup analyses by type of corticosteroid , most of the beneficial and harmful effects were attributable to dexamethasone ; hydrocortisone had little effect on any outcomes except for an increase in intestinal perforation and a borderline reduction in patent ductus arteriosus . AUTHORS ' CONCLUSIONS The benefits of early postnatal corticosteroid treatment ( ≤ 7 days ) , particularly dexamethasone , may not outweigh the adverse effects of this treatment . Although early corticosteroid treatment facilitates extubation and reduces the risk of chronic lung disease and patent ductus arteriosus , it causes short-term adverse effects including gastrointestinal bleeding , intestinal perforation , hyperglycaemia , hypertension , hypertrophic cardiomyopathy and growth failure . Long-term follow-up studies report an increased risk of abnormal neurological examination and cerebral palsy . Hydrocortisone in the doses and regimens used in the reported RCTs has few beneficial or harmful effects and can not be recommended for the prevention of chronic lung disease
MS21804	*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: An educational training program for children with asthma , aged between 8 and 13 years , was evaluated in an 18-month r and omized , controlled experiment , including three follow-up evaluations . The objective of the program is to improve coping with asthma in daily life . The program , ten 1-hour sessions , is a combination of self-management training and cognitive behaviour therapy in a group , using games and learning material s specifically design ed for this age group . From 195 asthmatic children , 112 with inadequate self-management abilities were selected ; these children were r and omly divided into an experimental group and two control groups . The results indicated highly significant differences in favor of the experimental group on the psychological and medical variables . There were no drop-outs during the program . The conclusion is that this multi-faceted program is an effective method of teaching children how to cope with their asthma and helping them to achieve a less anxious and more realistic attitude towards their illness AIM This article describes a study that aim ed to investigate the effect of nurse-delivered behaviour therapy on anxiety levels and quality of life in children with asthma and coexistent anxiety . METHOD A prospect i ve cohort pilot study in which ten children , aged between seven and ten years , with asthma and diagnosed with health-related anxiety took part . Data were collected over a two-year period , cognitive behaviour therapy sessions were provided , and asthma , anxiety and quality of life scores were measured . FINDINGS The Child and Adolescent Mental Health Services-devised , respiratory nurse-delivered , cognitive behaviour therapy programme was associated with an increase in quality of life for children with asthma and a decrease in anxiety levels and hyperventilation scores . CONCLUSION All nursing staff need to be aware of the detrimental effects of anxiety on asthma control , so that early symptoms of anxiety can be identified and addressed quickly The hierarchy of evidence in assessing the effectiveness of interventions or treatments is explained , and the gold st and ard for evaluating the effectiveness of interventions , the r and omised controlled trial , is discussed . Issues that need to be considered during the critical appraisal of r and omised controlled trials , such as assessing the validity of trial methodology and the magnitude and precision of the treatment effect , and deciding on the applicability of research results , are discussed . Important terminologies such as r and omisation , allocation concealment , blinding , intention to treat , p values , and confidence intervals are explained This study examined whether cognitive behavioural therapy ( CBT ) could prevent the development or worsening of panic-spectrum psychopathology and anxiety symptoms in chronic obstructive pulmonary disease ( COPD ) . 41 patients with COPD , who had undergone pulmonary rehabilitation , were r and omised to either a four-session CBT intervention condition ( n = 21 ) or a routine care condition ( n = 20 ) . Assessment s were at baseline , post-intervention , and at 6- , 12- and 18-month follow-ups . Primary outcomes were the rates of panic attacks , panic disorder and anxiety symptoms . Secondary outcomes were depressive symptoms , catastrophic cognitions about breathing difficulties , disease-specific quality of life and hospital admission rates . There were no significant differences between the groups on outcome measures at baseline . By the 18-month follow-up assessment , 12 ( 60 % ) routine care group participants had experienced at least one panic attack in the previous 6 months , with two ( 17 % ) of these being diagnosed with panic disorder , while no CBT group participants experienced any panic attacks during the follow-up phase . There were also significant reductions in anxiety symptoms and catastrophic cognitions in the CBT group at all three follow-ups and a lower number of hospital admissions between the 6- and 12-month follow-ups . The study provides evidence that a brief , specifically targeted CBT intervention can treat panic attacks in COPD patients and prevent the development and worsening of panic-spectrum psychopathology and anxiety symptoms Abstract Several behavioral medicine interventions ( eg , relaxation training and written emotional expression ) have been proposed as effective supplemental treatments for individuals with chronic illnesses such as asthma . Whether these treatments are feasible or effective in a manual-based , self-administered format is unclear , and few studies have examined the effectiveness of such treatments presented in a complementary format . We examined the feasibility and effectiveness of a 4 week stress management treatment compared with a matched placebo intervention in young adults with asthma . Both groups considered the workbooks credible treatment interventions and completed them conscientiously . The treatment group showed significant improvement in measures of lung function compared with the placebo group , but analysis revealed no differences in measures of perceived stress . These findings provide initial support for the feasibility of self-administered manual-based interventions and some evidence that they can produce health benefits in individuals with asthma and , perhaps other chronic conditions There is evidence that educational programmes may improve patient 's compliance with asthma treatment and control symptoms . Whilst medical parameters have been thoroughly studied , few data are available concerning psychological intervention . The aim of our open pilot study was to verify whether any difference in perceived illness and response style to asthma existed in the patients enrolled in an Asthma Rehabilitation Group ( ARG ) and in a Control Group ( CG ) . Forty consecutive asthmatics were r and omly enrolled , all of whom were diagnosed , treated and followed-up according to the International Guidelines . Both groups underwent a psychological assessment at baseline and after one year . A battery of question naires was used to obtain data relating to baseline characteristics ( anxiety , depression , psychophysiological disorders ) , emotional reactions to asthma attacks ( panic-fear , etc , ) and cognitive variables ( external control , psychological stigma , internal beliefs , external chance , etc . ) involved in the perceived illness . In addition , the Asthma Rehabilitation Group patients underwent an educational programme and a cognitive-behavioural intervention . In both groups , a reduction of anxiety and depression scores was observed , as well as a significant improvement of the medical parameters evaluated . Only the Asthma Rehabilitation Group reported lower scores on the Psychophysiological Question naire and on the External Control Subscale after 1 year . The Control Group reported higher score on the External Chance Scale . The data of our study seem to confirm the effectiveness of psychological intervention on the cognitive skills involved in the perception and management of asthma . Larger scale studies on this topic are suggested This study tested the efficacy of a nurse-administered 8-week group treatment program for adults with asthma suffering from coexisting panic disorder . The program consisted of cognitive behavioral treatment ( CBT ) for panic disorder combined with asthma education ( AE ) . Forty-eight women with a confirmed diagnosis of asthma and panic disorder were r and omly allocated to a treatment condition ( n=25 ) and a wait-list control condition ( n=23 ) . Twenty-five participants —15 in the treatment group and 10 in the wait-list control group— completed treatment . Repeated measures ANOVA procedures were used to compare the groups on panic and asthma outcomes at posttreatment and 6-month follow-up . The results demonstrate that the CBT-AE program is capable of producing substantial and durable antipanic and antianxiety treatment effects and led to substantial but nonsustained improvement in morning peak-flow expiratory rate and asthma-related quality of life . Implication s of these findings for this clinical population are addressed Confusion between panic and asthma symptoms can result in serious self-management errors . A cognitive behavior psychophysiological therapy ( CBPT ) intervention was culturally adapted for Latinos consisting of CBT for panic disorder ( PD ) , asthma education , differentiation between panic and asthma symptoms , and heart rate variability biofeedback . An RCT compared CBPT to music and relaxation therapy ( MRT ) , which included listening to relaxing music and paced breathing at resting respiration rates . Fifty-three Latino ( primarily Puerto Rican ) adults with asthma and PD were r and omly assigned to CBPT or MRT for 8 weekly sessions . Both groups showed improvements in PD severity , asthma control , and several other anxiety and asthma outcome measures from baseline to post-treatment and 3-month follow-up . CBPT showed an advantage over MRT for improvement in adherence to inhaled corticosteroids . Improvements in PD severity were mediated by anxiety sensitivity in CBPT and by depression in MRT , although earlier levels of these mediators did not predict subsequent improvements . Attrition was high ( 40 % ) in both groups , albeit comparable to CBT studies targeting anxiety in Latinos . Additional strategies are needed to improve retention in this high-risk population . Both CBPT and MRT may be efficacious interventions for comorbid asthma-PD , and CBPT may offer additional benefits for improving medication adherence An individualised asthma programme directed at behavioural change was evaluated in asthmatic subjects who reported complaints and impairment , despite adequate medical treatment . Mild-to-moderate asthma patients ( n=23 ) were r and omly assigned to a programme or waiting list condition . Outcome measures were : McMaster Asthma Quality of Life Question naire , Asthma Symptom Checklist , Negative Emotionality Scale , Knowledge , Attitude and Self-Efficacy Asthma Question naire , Adherence Scale , and peak flow measurements . Both groups were evaluated at three consecutive moments , each separated by 3 months ; the programme was delivered between the first two evaluations . At onset the patient received a workbook containing information , exercises and homework assignments . Psycho-education , behavioural and cognitive techniques were introduced during six 1‐h individual sessions . Compared with controls the programme group reported less symptoms ( obstruction , fatigue ) , better quality of life ( activity , symptoms , emotions ) , decreased negative affectivity , and increased adherence , immediately after finishing the programme and at 3 months follow-up . All three cognitive variables ( knowledge , attitude towards asthma , self-efficacy ) and day and night peak flow ratings improved in the programme group but not in the waiting list group . Participation in an individualised programme result ed in improvement of asthma morbidity , and asthma-related behaviour and cognitions , in subjects reporting symptoms and impairment despite adequate medical therapy BACKGROUND High levels of asthma-related fear and panic exacerbate asthma symptoms and complicate the management of asthma . Asthma-specific fear may be reduced by a cognitive behavioural intervention . We aim ed to test if there is a reduction in asthma-specific fear after cognitive behavioural intervention compared with routine treatment . METHODS Adults with asthma registered with family doctors in Sheffield UK were screened for anxiety and 94 highly anxious patients were r and omly allocated to receive either a cognitive behavioural intervention to improve self-management of their anxiety ( n = 50 ) or routine clinical care ( n = 44 ) . Asthma-specific fear at the end of treatment and at six month follow up were the primary endpoints . Service usage in the six months prior to and six months following the intervention was monitored to allow estimation of costs . Data were analysed by intention to treat . FINDINGS At the end of treatment , there was a significantly greater reduction in asthma-specific fear for people in the CBT group compared with controls . At six months after treatment the reduction in asthma-specific fear in the CBT group was increased and the difference between treatment and control group was statistically significant . Service use costs were not reduced in the CBT group . INTERPRETATION A brief cognitive behavioural intervention was found to have efficacy in reducing asthma-specific panic fear immediately after treatment and at 6 months follow up . There was no cost advantage to cognitive behavioural treatment ABSTRACT Objectives : Evidence for the efficacy of Cognitive Behavioural Therapy ( CBT ) in asthma is developing but it is not known if this translates to benefits in severe asthma or if a group approach is acceptable to this patient group . This study aim ed to assess the feasibility and acceptability of Group-CBT in severe asthma . Method : This was a two-centre , r and omised controlled parallel group feasibility study . Eligible participants ( patients with severe asthma and a clinical ly significant diagnosis of anxiety and /or depression – Hospital Anxiety and Depression Scale ( HAD ) score greater than 8 for the anxiety or depression sub-scale ) received Group-CBT in weekly sessions for eight consecutive weeks and usual care or usual care only . Follow-up was for 16 weeks and end points were : Asthma Quality of Life Question naire , Asthma Control Question naire , HAD , Dyspnoea-12 , EuroQual-5D and EuroQuol-VAS . Results : 51 patients were r and omised : 36 % ( 51 out of 140 ) consent rate and attrition at week 16 was 12 . Screening logs indicated that study take-up was influenced by patients living long distances from the treatment centre and inability to commit to the weekly dem and s of the programme . Drop-out was higher in Group-CBT compared due to inability to commit to the weekly programme because of poor health . Participants who contributed to focus group discussion s reported that Group-CBT contributed to a better underst and ing of their illness and related approaches to anxiety management and acceptance of their asthma condition . Although weekly face-to-face sessions were challenging , this was the preferred method of delivery for these participants . Conclusions : This feasibility study shows that Group-CBT warrants further investigation as a potentially promising treatment option for patients with severe asthma . It has been possible but not easy to recruit and retain the sample . Options for a less dem and ing intervention schedule , such as less frequent face-to-face visits and the use of web-based interventions , require careful consideration Output:	Studies were more likely to indicate beneficial effects where anxiety-focused ( rather than illness-focused ) intervention protocol s were utilised , asthma-related education was provided and where the trials focused on individuals with likely clinical levels of anxiety at baseline . Whilst further high- quality research is needed , available evidence is supportive of anxiety-focused CBT interventions tailored to target the particular mechanisms thought to maintain this comorbidity in asthma
MS21805	*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 Obese women with the polycystic ovary syndrome are relatively unresponsive to the induction of ovulation by clomiphene . We hypothesized that reducing insulin secretion by administering metformin would increase the ovulatory response to clomiphene . METHODS We performed oral glucose-tolerance tests before and after the administration of 500 mg of metformin or placebo three times daily for 35 days in 61 obese women with the polycystic ovary syndrome . Women who did not ovulate spontaneously were then given 50 mg of clomiphene daily for five days while continuing to take metformin or placebo . Serum progesterone was measured on days 14 , 28 , 35 , 44 , and 53 , and ovulation was presumed to have occurred if the concentration exceeded 8 ng per milliliter ( 26 nmol per liter ) on any of these days . RESULTS Twenty-one women in the metformin group and 25 women in the placebo group were given clomiphene because they did not ovulate spontaneously during the first phase of the study . Among the 21 women given metformin plus clomiphene , the mean ( + /-SE ) area under the serum insulin curve after oral glucose administration decreased from 6745+/-2021 to 3479+/-455 microU per milliliter per minute ( 40.5+/-12.1 to 20.9+/-2.7 nmol per liter per minute , P=0.03 ) , but it did not change significantly in the 25 women given placebo plus clomiphene . Nineteen of the 21 women ( 90 percent ) who received metformin plus clomiphene ovulated ( mean peak serum progesterone concentration , 23.8+/-3.4 ng per milliliter [ 7.6+/-10.9 nmol per liter ] ) . Two of the 25 women ( 8 percent ) who received placebo plus clomiphene ovulated ( P<0.001 ) . Overall , 31 of the 35 women ( 89 percent ) treated with metformin ovulated spontaneously or in response to clomiphene , as compared with 3 of the 26 women ( 12 percent ) treated with placebo . CONCLUSIONS The ovulatory response to clomiphene can be increased in obese women with the polycystic ovary syndrome by decreasing insulin secretion with metformin Abdominal obesity and hyperinsulinemia play a key role in the development of the polycystic ovary syndrome ( PCOS ) . Dietary-induced weight loss and the administration of insulin-lowering drugs , such as metformin , are usually followed by improved hyper and rogenism and related clinical abnormalities . This study was carried out to evaluate the effects of combined hypocaloric diet and metformin on body weight , fat distribution , the glucose-insulin system , and hormones in a group of 20 obese PCOS women [ body mass index ( BMI ) > 28 kg/m2 ] with the abdominal phenotype ( waist to hip ratio > 0.80 ) , and an appropriate control group of 20 obese women who were comparable for age and pattern of body fat distribution but without PCOS . At baseline , we measured sex hormone , sex hormone-binding globulin ( SHBG ) , and leptin blood concentrations and performed an oral glucose tolerance test and computerized tomography ( CT ) at the L4-L5 level , to measure sc adipose tissue area ( SAT ) and visceral adipose tissue area . All women were then given a low-calorie diet ( 1,200 - 1,400 kcal/day ) alone for one month , after which anthropometric parameters and CT scan were newly measured . While continuing dietary treatment , PCOS women and obese controls were subsequently placed , in a r and om order , on metformin ( 850 mg/os , twice daily ) ( 12 and 8 , respectively ) or placebo ( 8 and 12 , respectively ) , according to a double-blind design , for the following 6 months . Blood tests and the CT scan were performed in each woman at the end of the study while they were still on treatment . During the treatment period , 3 women of the control group ( all treated with placebo ) were excluded because of noncompliance ; and 2 PCOS women , both treated with metformin , were also excluded because they became pregnant . Therefore , the women cohort available for final statistical analysis included 18 PCOS ( 10 treated with metformin and 8 with placebo ) and 17 control women ( 8 treated with metformin and 9 with placebo ) . The treatment was well tolerated . In the PCOS group , metformin therapy improved hirsutism and menstrual cycles significantly more than placebo . Baseline anthropometric and CT parameters were similar in all groups . Hypocaloric dieting for 1 month similarly reduced BMI values and the waist circumference in both PCOS and control groups , without any significant effect on CT scan parameters . In both PCOS and control women , however , metformin treatment reduced body weight and BMI significantly more than placebo . Changes in the waist-to-hip ratio values were similar in PCOS women and controls , regardless of pharmacological treatment . Metformin treatment significantly decreased SAT values in both PCOS and control groups , although only in the latter group were SAT changes significantly greater than those observed during the placebo treatment . On the contrary , visceral adipose tissue area values significantly decreased during metformin treatment in both PCOS and control groups , but only in the former was the effect of metformin treatment significantly higher than that of placebo . Fasting insulin significantly decreased in both PCOS women and controls , regardless of treatment , whereas glucose-stimulated insulin significantly decreased only in PCOS women and controls treated with metformin . Neither metformin or placebo significantly modified the levels of LH , FSH , dehydroepi and rosterone sulphate , and progesterone in any group , whereas testosterone concentrations decreased only in PCOS women treated with metformin . SHBG concentrations remained unchanged in all PCOS women ; whereas in the control group , they significantly increased after both metformin and placebo . Leptin levels decreased only during metformin treatment in both PCOS and control groups . ( ABSTRACT TRUNCATED BACKGROUND Insulin resistance and increased ovarian cytochrome P450c17 alpha activity are both features of the polycystic ovary syndrome . P450c17 alpha , which is involved in and rogen bio synthesis , has both 17 alpha-hydroxylase and 17,20-lyase activities . Increased activity of this enzyme results in exaggerated conversion of progesterone to 17 alpha-hydroxyprogesterone in response to stimulation by gonadotrophin . We hypothesized that hyperinsulinemia stimulates ovarian P450c17 alpha activity . METHODS We measured fasting serum steroid concentrations and the response of serum 17 alpha-hydroxyprogesterone to leuprolide , a gonadotrophin-releasing hormone agonist , and performed oral glucose-tolerance tests before and after oral administration of either metformin ( 500 mg three times daily ) or placebo for four to eight weeks in 24 obese women with the polycystic ovary syndrome . RESULTS In the 11 women given metformin , the mean ( + /- SE ) area under the serum insulin curve after oral glucose administration decreased from 9303 + /- 1603 to 4982 + /- 911 microU per milliliter per minute ( 56 + /- 10 to 30 + /- 6 nmol per liter per minute ) ( P = 0.004 ) . This decrease was associated with a reduction in the basal serum 17 alpha-hydroxyprogesterone concentration from 135 + /- 21 to 66 + /- 7 ng per deciliter ( 4.1 + /- 0.6 to 2.0 + /- 0.2 nmol per liter ) ( P = 0.01 ) and a reduction in the leuprolide-stimulated peak serum 17 alpha-hydroxyprogesterone concentration from 455 + /- 54 to 281 + /- 52 ng per deciliter ( 13.7 + /- 1.6 to 8.5 + /- 1.6 nmol per liter ) ( P = 0.01 ) . The serum 17 alpha-hydroxyprogesterone values increased slightly in the placebo group . In the metformin group , the basal serum luteinizing hormone concentration decreased from 8.5 + /- 2.2 to 2.8 + /- 0.5 mlU per milliliter ( P = 0.01 ) , the serum free testosterone concentration decreased from 0.34 + /- 0.07 to 0.19 + /- 0.05 ng per deciliter ( 12 + /- 3 to 7 + /- 2 pmol per liter ) ( P = 0.009 ) , and the serum sex hormone-binding globulin concentration increased from 0.8 + /- 0.2 to 2.3 + /- 0.6 microgram per deciliter ( 29 + /- 7 to 80 + /- 21 nmol per liter ) ( P < 0.001 ) . None of these values changed significantly in the placebo group . CONCLUSIONS In obese women with the polycystic ovary syndrome , decreasing serum insulin concentrations with metformin reduces ovarian cytochrome P450c17 alpha activity and ameliorates hyper and rogenism BACKGROUND This study aims to evaluate the impact of metformin on ovarian response when co-administered during recombinant (r)FSH using the low-dose step-up protocol in clomiphene citrate-resistant polycystic ovarian syndrome ( PCOS ) patients with normal glucose tolerance . METHODS AND RESULTS Thirty-two patients were r and omized to metformin ( n = 16 ) and placebo ( n = 16 ) groups . Hormonal assessment , a 75 g oral glucose tolerance test ( OGTT ) and a frequently sample d i.v . glucose tolerance test ( FSIGTT ) were performed before and after oral administration of metformin ( 850 mg twice daily ) or placebo for 6 weeks . Recombinant FSH treatment was undertaken , thereafter , in women who did not ovulate on metformin ( n = 10 ) or placebo ( n = 15 ) . There was no significant change in all insulin sensitivity indices in both groups . The only change noted was a decline in mean serum free testosterone concentration in the metformin group ( P = 0.049 ) . One patient on placebo and six patients on metformin ovulated spontaneously ( P < 0.05 ) . All parameters of ovarian response were comparable between the two groups during rFSH treatment . Combining the 6 week placebo or metformin-only period with a single rFSH treatment cycle , the overall ovulation rates were 75 and 94 % in the placebo and metformin groups respectively ( P > 0.05 ) . The respective figures for pregnancy were 6.3 and 31.3 % ( P > 0.05 ) . CONCLUSIONS Metformin may restore ovulation with no improvement on insulin resistance in clomiphene citrate-resistant PCOS patients with normal glucose tolerance , but has no significant effect on ovarian response during rFSH treatment OBJECTIVE To evaluate the effect of metformin therapy on hyper and rogenism , insulin resistance , cervical scores , ovulation , and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome ( PCOS ) . DESIGN Prospect i ve , r and omized , double-blind , placebo-controlled study . SETTING Infertility clinic of a tertiary referral center . PATIENT(S ) Fifty-six women with clomiphene citrate-resistant PCOS . INTERVENTION(S ) Two cycles of oral metformin therapy ( 850 mg , twice daily ) in group I and placebo therapy ( twice daily ) in group II . Clomiphene citrate ( 100 mg/day ) on cycle days 3 - 7 of the second cycle in both groups . MAIN OUTCOME MEASURE(S ) Insulin , T , DHEAS , FSH , LH , body mass index ( BMI ) , waist-to-hip ratio , endometrial thickness , cervical score , ovulation , and pregnancy rates in clomiphene-induced cycles after metformin therapy . RESULT ( S ) Metformin therapy result ed in a significant decrease in total T , LH level , LH/FSH ratio , insulin resistance , and mean BMI . No difference in waist-to-hip ratio , DHEAS level , and fasting insulin level was observed . Clomiphene citrate induction result ed in higher ovulation rates and thicker endometrium in the metformin group than in the placebo group . There was higher cumulative pregnancy rate in the metformin group ; however , there was no significant difference in the pregnancy rate between the two groups . CONCLUSION ( S ) Metformin therapy not only decreases hyper and rogenism and insulin resistance but also improves ovulation rates , cervical scores , and pregnancy rates in clomiphene citrate-resistant women with PCOS We hypothesized that hyperinsulinemia contributes to early pregnancy loss in the polycystic ovary syndrome by adversely affecting endometrial function and environment . Serum glycodelin , a Output:	Metformin has an effect in reducing fasting insulin concentrations , blood pressure , and low density lipoprotein cholesterol . We found no evidence of any effect on body mass index or waist : hip ratio . Metformin was associated with a higher incidence of nausea , vomiting , and other gastrointestinal disturbance . CONCLUSIONS Metformin is an effective treatment for anovulation in women with polycystic ovary syndrome . No data are available regarding the safety of metformin in long term use in young women and only limited data on its safety in early pregnancy .
MS21806	*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 Variability in patients ' response to interventions in pain and other clinical setting s is large . Many explanations such as trial methods , environment or culture have been proposed , but this paper sets out to show that the main cause of the variability may be r and om chance , and that if trials are small their estimate of magnitude of effect may be incorrect , simply because of the r and om play of chance . This is highly relevant to the questions of ‘ How large do trials have to be for statistical accuracy ? ’ and ‘ How large do trials have to be for their results to be clinical ly valid ? ’ The true underlying control event rate ( CER ) and experimental event rate ( EER ) were determined from single‐dose acute pain analgesic trials in over 5000 patients . Trial group size required to obtain statistically significant and clinical ly relevant ( 0.95 probability of number‐needed‐to‐treat within ±0.5 of its true value ) results were computed using these values . Ten thous and trials using these CER and EER values were simulated using varying group sizes to investigate the variation due to r and om chance alone . Most common analgesics have EERs in the range 0.4–0.6 and CER of about 0.19 . With such efficacy , to have a 90 % chance of obtaining a statistically significant result in the correct direction requires group sizes in the range 30–60 . For clinical relevance nearly 500 patients are required in each group . Only with an extremely effective drug ( EER>0.8 ) will we be reasonably sure of obtaining a clinical ly relevant NNT with commonly used group sizes of around 40 patients per treatment arm . The simulated trials showed substantial variation in CER and EER , with the probability of obtaining the correct values improving as group size increased . We contend that much of the variability in control and experimental event rates is due to r and om chance alone . Single small trials are unlikely to be correct . If we want to be sure of getting correct ( clinical ly relevant ) results in clinical trials we must study more patients . Credible estimates of clinical efficacy are only likely to come from large trials or from pooling multiple trials of conventional ( small ) size Successful management of endodontic pain represents a continuing challenge . The purpose of this r and omized , double-blind , placebo-controlled , parallel-group trial was to compare the pain reducing effect of oral preparations of meloxicam , piroxicam , and placebo in endodontic emergency patients . A total of 51 patients who presented to the Tehran University endodontic clinic and one private dental clinic were invited to participate . Patients were asked to evaluate their pretreatment pain with a visual-analog scale . After root canal therapy they were r and omly assigned to one of three groups : meloxicam , piroxicam , or placebo . Each patient was sent home with a visual-analog scale to fill out at 8 and 24 h after completion of therapy . The results of this study showed no significant differences between efficacy of meloxicam , piroxicam , and placebo , but a significant effect of the time factor in reducing postoperative pain in all treatment groups was observed Abstract A previously established relationship for deriving dichotomous from continuous information in r and omised controlled trials ( RCTs ) of analgesics has been tested using an independent data set . Individual patient information from 18 RCTs of parallel‐group design in acute postoperative pain ( after abdominal , gynaecological and oral surgery ) was used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) and the proportion of patients with > 50%maxTOTPAR for the different treatments . The relationship between the measures was investigated in 85 treatments with over 3400 patients . In 80 of 85 treatments ( 94 % ) agreement between calculated and actual number of patients with > 50%maxTOTPAR was within four patients per treatment and in 72 ( 85 % ) was within three ( average of 40 patients per treatment , range 21–58 patients ) . Summing the positive and negative differences between actual and calculated numbers of patients with > 50%maxTOTPAR gave an average difference of 0.30 patients per treatment arm . Reports of RCTs of analgesics frequently describe results of studies in the form of mean derived indices , rather than using discontinuous events , such as number or proportion of patients with 50 % pain relief . Because mean data inadequately describe information with a non‐normal distribution , combining mean data in systematic review s may compromise the results . Showing that dichotomous data can reliably be derived from mean data in acute pain studies enables data published as means to be used for quantitative systematic review s which require data in dichotomous form & NA ; Reports of RCTs of analgesics frequently describe results of studies in the form of mean derived indices , rather than using discontinuous events — such as number or proportion of patients with 50 % pain relief . Because mean data inadequately describe information with a non‐normal distribution , combining mean data in systematic review s may compromise the results . Showing that dichotomous data can reliably be derived from mean data , at least in acute pain models , indicates that more meaningful overviews or meta‐ analysis may be possible . This study investigated the relationship between continuous and dichotomous analgesic measures in a set of individual patient data , and then used that relationship to derive dichotomous from continuous information in r and omised controlled trials ( RCTs ) of analgesics . Individual patient information from 13 RCTs of parallel‐group and crossover design in acute postoperative pain was used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) and the proportion of patients with greater than 50 % pain relief ( > 50%maxTOTPAR ) for the different treatments . The relationship between the measures was investigated in 45 actual treatments and 10 000 treatments simulated using the underlying actual distribution ; 1283 patients had 45 separate treatments . Mean % maxTOTPAR correlated with the proportion of patients with > 50%maxTOTPAR ( r2 = 0.90 ) . The relationship calculated from all the 45 treatments predicted to within three patients the number of patients with more than 50 % pain relief in 42 of 45 treatments , and 98.8 % of 10 000 simulated treatments . For seven effective treatments , actual numbers‐needed‐to‐treat ( NNT ) to achieve > 50%maxTOTPAR compared with placebo were very similar to those derived from calculated data AIM To investigate the effect of the administration of a single dose of meloxicam pre-emptively on postoperative pain management in patients who underwent inguinal hernia repair under local anaesthesia . SUBJECTS AND METHOD Fifty patients who underwent inguinal hernia repair under local anaesthesia during the period November 2005 to May 2006 were recruited into the study prospect ively . The patients were r and omized to two groups regarding administration and non-administration of pre-emptive meloxicam . The postoperative visual analogue pain scale ( VAS ) values at 4 , 8 , 12 and 24 hours and analgesic needs of the patients were recorded RESULTS No difference was found between the groups in terms of age , gender , hernia localization and type . The VAS values of the patients regarding their pain severity were evaluated at 4 , 8 , 12 and 24 hours and were significantly lower in the group which received meloxicam pre-emptively ( p = 0.001 , 0.0001 , 0.003 and 0.0001 respectively ) . The need for non-steroidal anti-inflammatory drug was also found to be significantly lower ( p = 0.0001 ) . CONCLUSION Postoperative pain severity and hence analgesic requirement were significantly decreased in the patients who received meloxicam pre-emptively . Single dose pre-emptive meloxicam seems to be an effective analgesic therapy for patients undergoing inguinal hernia repair under local anaesthesia . It thereby improves patients comfort and should be considered for use in outpatient surgery We studied 36 patients , allocated r and omly to receive meloxicam 15 mg rectally ( n = 18 ) or placebo suppository ( n = 18 ) before total abdominal hysterectomy in a double-blind study . Visual analogue scores for pain at rest ( P < 0.005 ) , on movement ( P < 0.05 ) and on coughing ( P < 0.05 ) were significantly decreased in the meloxicam group during the first 24 h after surgery . Mean 24-h PCA morphine requirements were 33.2 ( SD 16.9 ) mg and 38.2 ( 20.8 ) mg in the meloxicam and placebo groups , respectively ( ns ) . There was no difference in the incidence of nausea , vomiting or sedation between groups & NA ; A data base of r and omised clinical trials ( RCTs ) in pain research published from 1950 to 1990 was created following an extensive literature search . By applying a refined MEDLINE search strategy from 1966 to 1990 and by h and ‐ search ing more than 1 000 000 pages of a total of 40 biomedical journals published during the period 1950–1990 , more than 8000 RCTs were identified . The RCTs were published in more than 800 journals and over 85 % appeared between 1976 and 1990 . If the trend of the last 15 years persists , a total of more than 15 000 RCTs will be published in pain relief by the year 2000 . A detailed description of methods to ensure efficient use of re sources during the identification , retrieval and management of the information in pain relief and other fields is given . Emphasis is made on the importance of refining MEDLINE search strategies , on the use of volunteers to h and ‐ search journals and on careful monitoring of each of the steps of the process . The potential uses of the data base to guide clinical and research decisions are discussed Abstract One way to ensure adequate sensitivity for analgesic trials is to test the intervention on patients who have established pain of moderate to severe intensity . The usual criterion is at least moderate pain on a categorical pain intensity scale . When visual analogue scales ( VAS ) are the only pain measure in trials we need to know what point on a VAS represents moderate pain , so that these trials can be included in meta‐ analysis when baseline pain of at least moderate intensity is an inclusion criterion . To investigate this we used individual patient data from 1080 patients from r and omised controlled trials of various analgesics . Baseline pain was measured using a 4‐point categorical pain intensity scale and a pain intensity VAS under identical conditions . The distribution of the VAS scores was examined for 736 patients reporting moderate pain and for 344 reporting severe pain . The VAS scores corresponding to moderate or severe pain were also examined by gender . Baseline VAS scores recorded by patients reporting moderate pain were significantly different from those of patients reporting severe pain . Of the patients reporting moderate pain 85 % scored over 30 mm on the corresponding VAS , with a mean score of 49 mm . For those reporting severe pain 85 % scored over 54 mm with a mean score of 75 mm . There was no difference between the corresponding VAS scores of men and women . Our results indicate that if a patient records a baseline VAS score in excess of 30 mm they would probably have recorded at least moderate pain on a 4‐point categorical scale Fifty patients were scheduled to undergo removal of symmetrically positioned lower third molars in two separate appointments . Meloxicam 7.5 or 15 mg was once daily administered in a double-blind , r and omized and crossover manner after the surgery for 4 days . Objective and subjective parameters were recorded for comparison of postoperative courses . Patients treated with 7.5 mg meloxicam who underwent osteotomy reported higher pain scores at 1.5 , 3 , 4 , 10 , 12 and 16 h ( P<0.05 ) and ingested a greater amount of rescue analgesic medication ( P<0.05 ) than those who did not require osteotomy . A higher percentage of patients who underwent osteotomy medicated with 7.5 mg meloxicam needed rescue medication as compared to those who did not require osteotomy ( P<0.05 ) . There was a similar mouth opening at suture removal compared with preoperative values for both doses ( P>0.05 ) . There were no significant differences concerning swelling observed on the 2nd or 7th postoperative days in comparison with baseline ( P>0.05 ) between the two doses . Pain , trismus and swelling after lower third molar removal not requiring osteotomy can be successfully controlled by a dose regimen of 7.5 mg meloxicam once daily . For more aggressive extraction s 15 mg meloxicam is advisable OBJECTIVES To investigate pain relieving efficacy of six agents which are used in postoperative pain management after otolaryngologic operations . PATIENTS AND METHODS 120 adult patients ( 63 females , 57 males ; mean age 36 ; range 18 to 76 years ) were included in the study . The same intraoperative anesthesia was applied to all the patients . The following medications were r and omly given to the patients who declared pain in the sixth hour after the operation : naproxen sodium , meloxicam , rofecoxib , paracetamol , dipyrone , and etodolac in proper dosage to form groups of 20 for each medication . Before and after the application of pain reliever tablets , visual analog scale ( VAS ) and numerical rating scale ( NRS ) were used to inquire whether the agents were effective in relieving pain . ANOVA ( one way ) , paired t-test , Kruskal-Wallis , and Student 's t-test were used as statistical methods . p values < 0.05 were considered to indicate statistical significance . RESULTS All the groups had similar VAS values before medication ( p>0.05 ) . When VAS values of each group were assessed after medication Output:	AUTHORS ' CONCLUSIONS In the absence of evidence of efficacy , at present , for oral meloxicam in acute postoperative pain , its use in this indication is not justified .
MS21807	*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: On-dem and therapy is effective for maintaining symptoms control in nonerosive gastroesophagealreflux disease ( GERD ) . Our aim was to assess the clinical effectiveness of on-dem and therapy witha proton pump inhibitor ( PPI ) in mild GERD ( nonerosive and low- grade esophagitis ) , its impact onhealth-related quality of life ( HRQoL ) , and the degree of patient satisfaction . Fifty-five patients ( 17with nonerosive GERD and 38 with low- grade esophagitis ) were treated with rabeprazole , 20 mg/day . The healed patients started on-dem and therapy . We evaluated symptoms ( clinical question naire),HRQoL ( SF-36 question naire ) , and patient satisfaction ( visual analogue scale ) . Of the 55 patients included , 51 started on-dem and therapy for 6 months . Symptom control ( heartburn < twice a week)was achieved in over 85 % of the patients . The mean ( SD ) amount of PPI used was 0.3 (0.19)tablet/day . The patient satisfaction score at the end of the acute phase was 98 ( range , 0 - 100 ) and remained high ( 90 ; range , 10 - 100 ) and stable during on-dem and therapy . Short-term treatmentnormalized the HRQoL scores , which were subsequently maintained during on-dem and therapy . On-dem and therapy is useful for the clinical management of patients with mild GERD , allowingadequate symptoms control , limiting PPI consumption , and affording important patient satisfactionwith normalization of BACKGROUND & AIMS Gastroesophageal reflux is considered a common condition , but detailed population -based data on reflux in the United States are lacking . The aim of this study was to determine the prevalence and clinical spectrum of gastroesophageal reflux in Olmsted County , Minnesota . METHODS A reliable and valid self-report question naire was mailed to an age- and sex-stratified r and om sample of 2200 Olmsted County residents aged 25 - 74 years . RESULTS The prevalence per 100 of heartburn and /or acid regurgitation experienced at least weekly was 19.8 ( 95 % confidence interval [ 95 % CI ] , 17.7 - 21.9 ) . Heartburn and acid regurgitation were associated with noncardiac chest pain ( odds ratio [ OR ] , 4.2 ; 95 % CI , 2.9 - 6.0 ) , dysphagia ( OR , 4.7 ; 95 % CI , 2.9 - 7.4 ) , dyspepsia ( OR , 3.1 ; 95 % CI , 1.9 - 5.0 ) , and globus sensation ( OR , 1.9 ; 95 % CI , 1.0 - 3.6 ) but not with asthma , hoarseness , bronchitis , or a history of pneumonia . Among subjects with reflux symptoms , 1.0 % reported an episode of hematemesis and 1.3 % had a past esophageal dilatation . CONCLUSIONS Symptoms of reflux are common among white men and women who are 25 - 74 years of age . Heartburn and acid regurgitation are significantly associated with chest pain , dysphagia , dyspepsia , and globus sensation . The percentage of patients reporting complications is low , but the absolute number is probably considerable given the high prevalence of the condition in the community To compare the efficacy of conventional versus on-dem and ( symptomatic ) treatment of duodenal ulcer , 81 patients were r and omized into two groups . Group A ( n = 40 ) patients were treated with ranitidine 150 mg twice daily until complete ulcer healing was achieved . Group B ( n = 41 ) received a similar dose of ranitidine until complete relief of pain was achieved , irrespective of ulcer healing . Recurrence of ulcer in group A was treated with a full course of treatment until complete healing of the ulcer was achieved again , whereas , in group B , treatment was given only until pain recurrence was symptomatically controlled . Endoscopic examination was performed each month . Analysis of the results at 8 wk and 28 wk showed that 1 ) ulcer healing in group A was significantly superior to that in group B up to 24 wk , but at 28 wk the difference was no longer statistically significant ( 95 % vs 70 % ) , 2 ) the number of painful days were similar in the two groups , 3 ) group A patients took treatment for a significantly longer period than those in group B , 4 ) the cost of treatment per patient in group A was significantly greater than that in group B , 5 ) the recurrence rate assessed in patients followed for 28 wk after complete ulcer healing was similar in the two groups , and 6 ) the ulcer-related complications were not significantly different in the two groups . These findings indicate that , although on-dem and treatment results in slower ulcer healing , it is not associated with an increase in the duration of pain and incidence of complications . A major advantage of this approach was a significant reduction in the cost of treatment . It is concluded that on-dem and treatment is an attractive alternative therapeutic approach in the management of duodenal ulcer disease The present study was performed to compare pain-related oesophageal motility , gastro-oesophageal reflux and ST-segment deviations in patients with intermittent chest pain and normal or pathological coronary angiography . Thirty patients ( 11 males , 19 females ; mean age 54.8 years ) with normal and 15 patients ( 12 males , 3 females ; mean age 66.7 years ) with pathological coronary angiography were investigated by 24-h oesophageal pressure , pH and ECG recording . Chest pain correlated with motility abnormalities or gastro-oesophageal reflux occurred in 33 % ( 10/30 ) of patients with normal coronary arteries and in 26 % of patients with pathological coronary angiography . Symptomatic and asymptomatic ST-segment changes were less frequently observed in patients with normal angiography ( 4/30 ) than in patients with pathological coronary angiography ( 7/14 ; P = 0.02 ) . Oesophageal dysfunction coincided with ST-segment deviation in 6.7 % ( 2/30 ) of patients with normal and 40 % ( 6/15 ) of patients with pathological coronary angiography ( P = 0.02 ) . The conclusions reached were : ( 1 ) pain-correlated abnormal motility or gastro-oesophageal reflux occurred in patients with normal and pathological coronary angiography at the same frequency ; ( 2 ) ambulatory motility and pH recording alone does not appear to differentiate between cardiac and non-cardiac chest pain ; ( 3 ) simultaneous ECG recording reveals a significant correlation of ST-segment deviation and gastro-oesophageal reflux or abnormal motility in patients with coronary artery stenosis The efficacy of fundoplication operations in the long-term management of gastroesophageal reflux disease ( GERD ) has been documented . However , only a few prospect i ve controlled series support the longterm ( > 10 years ) efficacy of these procedures , and further data are required to also determine whether the type of fundoplication affects the frequency of postfundoplication complaints . The aim of this study was to conduct a r and omized , controlled clinical trial to assess the long-term symptomatic outcome of a partial posterior fundoplication as compared to a total fundic wrap . During the years 1983 to 1991 , a total of 13 7 patients with chronic gastroesophageal reflux disease were enrolled in the study ; 72 were r and omized to semifundoplication ( Toupet ) and 65 to total fundoplication ( Nissen-Rossetti ) . A st and ardized symptom question naire was used for follow-up of these patients . A total of 110 patients completed a median follow-up of 11.5 years ; 54 had a total wrap and 56 underwent a partial posterior fundoplication . During this period , seven patients required reoperation ( Nissen-Rossetti in 5 and Toupet in 2 ) , 11 patients died , and nine patients were lost to follow-up or did not comply with the follow-up program . Control of heartburn ( no symptoms or mild , intermittent symptoms ) was achieved in 88 % and 92 % in the total and partial fundoplication groups , respectively , and the corresponding figures for control of acid regurgitation were 90 % and 94 % . We observed no difference in dysphagia scoring between the two groups , although odynophagia was somewhat more frequently reported in those undergoing a total fundoplication . On the other h and , a significant difference was observed in the prevalence of rectal flatus and postpr and ial fullness , which were recorded significantly more often in those undergoing a total fundoplication ( P < 0.001 and P < 0.03 , respectively ) . Posterior partial fundoplication seems to maintain the same high level of reflux control as total fundoplication . Earlier observations demonstrating the advantages of a partial fundoplication , which included fewer complaints associated with gas-bloat , continue to be valid after more than 10 years of follow-up Patients undergoing anaesthesia for cataract surgery were anaesthetized and their lungs ventilated by intermittent positive pressure ventilation . In one group , ventilation was facilitated by tracheal intubation and in the other group by laryngeal mask airway ( LMA ) . Reflux of stomach contents into the oesophagus was monitored continuously using an indwelling oesophageal pH electrode . The number of discrete episodes of reflux was higher in the LMA group ( P = 0.0178 ) , as was the incidence of reflux at antagonism of neuromuscular block ( P = 0.0349 ) Two hundred and sixty seven patients with duodenal ulceration were entered into a five year study of two strategies of treatment with cimetidine . Two thirds were treated continuously with 400 mg at bedtime supplemented by temporary increases in dosage if they had symptomatic relapses ( group 1 ) , and the remaining third were given intermittent “ healing ” doses for four to eight weeks if a symptomatic recurrence was judged to have occurred ( group 2 ) . Life table analysis showed that the probability of remaining free of clinical ly important symptoms five years after the start of treatment was 24 % ( 95 % confidence interval ( CI ) 15·5 % to 32·6 % ) in group 1 compared with nil in group 2 ( p<0·0001 ) . The median values for the longest periods free from relapse for each patient were 108 weeks in group 1 and 32 weeks in group 2 , respectively ( p<0·0001 ; 95 % CI of the median difference 36 to 76 ) . Over the five years 10 patients suffered major complications , two requiring emergency surgery , while a further nine had elective surgery because of the failure of medical treatment . There were no deaths that could be attributed either to ulceration or to treatment with cimetidine . Medical management was therefore very satisfactory for most patients , though those treated continuously with cimetidine suffered considerably less from their ulcer symptoms . As 80 % of patients studied relapsed during the two years after a healing course of cimetidine , continuous treatment will benefit many patients treated in general practice The head-downwards tipped position for physiotherapy has been cl aim ed to exacerbate gastro-oesophageal reflux ( GOR ) in infants with cystic fibrosis ( CF ) . This was investigated using lower oesophageal pH monitoring during physiotherapy . Twenty-one infants ( age range 1 - 27 months ) with respiratory disorders ( CF=11 ) , undergoing lower oesophageal pH monitoring were recruited . Subjects received two physiotherapy episodes in r and om order , A/B or B/A , 12 h apart . A began the gravity-assisted positioning head downward tip for : right lower lobe , middle lobe , left lower lobe and lingula ; then supine with no tip for anterior segments of the upper lobes followed by apical segments of upper lobes in a sitting position . B was in the reverse order . Intermittent chest clapping was carried out for 4 min in each position by a physiotherapist blinded to the pH data . During episode A , the median change in pH from baseline was -0.32 ( range -2.07 to + 1.0 ) in non-CF subjects ( NS ) and -0.52 ( range -2.7 to + 0.52 ) in CF subjects ( p<0.02 ) . During episode B , the median change in non-CF subjects was -0.1 ( NS ; range - 1.7 to -0.15 ) and in CF subjects was -0.05 ( NS ; range -0.67 to + 0.5 ) . There was no order effect for positioning . In the CF subjects the sitting position was twice as likely to have the lowest pH measurement during physiotherapy than the other positions ( p<0.04 ) . In conclusion , the head-downward tipped positioning for physiotherapy treatment neither induces nor aggravates gastro-oesophageal reflux . There is no justification for routinely changing the way in which infant physiotherapy is carried out BACKGROUND The length of time until symptom relief and the consistency of response are important aspects of the management of episodes of gastro-oesophageal reflux disease ( GORD ) . METHODS In an open , r and omized , crossover study 98 patients treated 3 episodes of GORD with ranitidine effervescent formulation and 3 with ranitidine st and ard formulation . The patients filled in a diary card during the 1st h after each study medication . Satisfaction with the formulations and the formulation of choice were determined at the Output:	Intermittent proton pump inhibitor or H2-receptor antagonist therapy is not effective in maintaining control in oesophagitis patients . H2-receptor antagonists are effective for relief of heartburn episodes . On-dem and proton pump inhibitor therapy may work in a proportion of non-erosive gastro-oesophageal reflux disease patients
MS21808	*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 improve health outcomes of children , the US Maternal and Child Health Bureau has recommended more effective organization of preventive services within primary care practice s and more coordination between practice s and community-based agencies . However , applying these recommendations in communities is challenging because they require both more complex systems of care delivery within organizations and more complex interactions between them . To improve the way that preventive health care services are organized and delivered in 1 community , we design ed , implemented , and assessed the impact of a health care system-level approach , which involved addressing multiple care delivery processes , at multiple levels in the community , the practice , and the family . Our objective was to improve the processes of preventive services delivery to all children in a defined geographic community , with particular attention to health outcomes for low-income mothers and infants . DESIGN Observational intervention study in 1 North Carolina county ( population 182 000 ) involving low- income pregnant mothers and their infants , primary care practice s , and departments of health and mental health . An interrupted time-series design was used to assess rates of preventive services in office practice s before and after the intervention , and a historical cohort design was used to compare maternal and child health outcomes for women enrolled in an intensive home visiting program with women who sought prenatal care during the 9 months before the program 's initiation . Outcomes were assessed when the infants reached 12 months of age . INTERVENTIONS Our primary objective was to achieve changes in the process of care delivery at the level of the clinical interaction between care providers and patients that would lead to improved health and developmental outcomes for families . We selected interventions that were directed toward major risk factors ( eg , poverty , ineffective care systems for preventive care in office practice s ) and for which there was existing evidence of efficacy . The interventions involved community- , practice - , and family-level strategies to improve processes of care delivery to families and children . The objectives of the community-level intervention were : 1 ) to achieve policy level changes that would result in changes in re sources available at the level of clinical care , 2 ) to engage multiple practice organizations in the intervention to achieve an effect on most , if not all , families in the community , and 3 ) to enhance communication between , among , and within public and private practice organizations to improve coordination and avoid duplication of services . The objective of the practice -level interventions was to overcome specific barriers in the process of care delivery so that preventive services could be effectively delivered . To assist the health department in implementing the family-level intervention , we provided assistance in hiring and training staff and ongoing consultation on staff supervision , including the use of structured protocol s for care delivery , and regular feedback data about implementation of the program . Interventions with primary care practice s focused on the design of the delivery system within the office and the use of teamwork and data in an " office systems " approach to improving clinical preventive care . All practice s ( N = 8) that enrolled at least 5 infants/month received help in assessing performance and developing systems ( eg , preventive services flow sheets ) for preventive services delivery . Family-level interventions addressed the process of care delivery to high-risk pregnant women ( < 100 % poverty ) and their infants . Mothers were recruited for the home visiting intervention when they first sought prenatal care at the community health center , the county 's largest provider of prenatal care to underserved women . The home visiting intervention involved teams of nurses and educators and involved 2 to 4 visits per month through the infant 's first year of life to provide parental education on fetal and infant health and development , enhance parents ' informal support systems , and link parents with needed health and human services . We included training in injury prevention and discipline , and home visitors assisted mothers in obtaining care from one of the primary care offices . RESULTS There were high levels of participation , changes in the organization of the delivery system , and improvements in preventive health outcomes . Agencies cooperated in joint contracting , staff training , and defining program eligibility . All 8 eligible practice s agreed to participate and 7/8 implemented at least 1 new office system element . Of eligible women , 89 % agreed to participate , and outcome data were available on 80 % ( 180/225 ) . After adjusting for differences in baseline characteristics , intervention group women were significantly more likely than comparison group women to use contraceptives ( 69 % vs 47 % ) , not smoke tobacco ( 27 % vs 54 % ) and have a safe and stimulating home environment for their children . Intervention group children were more likely to have had an appropriate number of well-child care visits ( 57 % vs 37 % ) and less likely to be injured ( 2 % vs 7 % ) . Intervention mothers also received Aid to Families with Dependent Children for fewer months after the birth of their child ( 7.7 months vs 11.3 months ) . CONCLUSIONS We observed a number of positive effects at all 3 levels of intervention . Policy-level changes at the state and community led to lasting changes in the organization and financing of care , which enabled changes in clinical services to take place . These changes have now been exp and ed beyond this community to other communities in the state . We were also able to engage multiple practice organizations , reduce duplication , and improve the coordination of care . Changes in the process of preventive services delivery were noted in participating practice s. Finally , the outcomes of the family-level intervention were comparable in direction and magnitude to the outcomes of previous r and omized trials of the intervention . All the changes were achieved over a relatively brief 3-year study period , and many have been sustained since the project was completed . Tiered , interrelated interventions directed at an entire population of mothers and children hold promise to improve the effectiveness and outcomes of health care for families and children BACKGROUND Community Action Against Asthma ( CAAA ) is a community-based participatory research ( CBPR ) project that assesses the effects of outdoor and indoor air quality on exacerbation of asthma in children , and tests household- and neighborhood-level interventions to reduce exposure to environmental asthma triggers . Representatives of community-based organizations , academia , an integrated health system , and the local health department work in partnership on CAAA 's Steering Committee ( SC ) to design and implement the project . OBJECTIVE To conduct a process evaluation of the CAAA community-academic partnership . DESIGN In-depth interviews containing open-ended questions were conducted with SC members . Analysis included established methods for qualitative data , including focused coding and constant comparison methods . SETTING Community setting in Detroit , Michigan . PARTICIPANTS Twenty-three members of the CAAA SC . MEASUREMENTS Common themes identified by SC members relating to the partnership 's ability to achieve project goals and the successes and challenges facing the partnership itself . MAIN RESULTS Identified partnership accomplishments included : successful implementation of a complex project , identification of children with previously undiagnosed asthma , and diverse participation and community influence in SC decisions . Challenges included ensuring all partners ' influence in decision-making , the need to adjust to " a different way of doing things " in CBPR , constraints and costs of doing CBPR felt by all partners , ongoing need for communication and maintaining trust , and balancing the needs of science and the community through intervention . CONCLUSIONS CBPR can enhance and facilitate basic research , but care must be given to trust issues , governance issues , organizational culture , and costs of participation for all organizations involved In this paper we describe a successful multi-level participatory intervention grounded in principles of individual and group empowerment , and guided by social construction theory . The intervention addressed known and persistent inequities in influenza vaccination among African American and Latino older adults , and associated infections , hospitalizations and mortality . It was design ed to increase resident ability to make informed decisions about vaccination , and to build internal and external infrastructure to support sustainability over time . The intervention brought a group of social scientists , vaccine research ers , geriatricians , public health nurses , elder services providers and advocates together with senior housing management and activist African American and Latino residents living in public senior housing in a small east coast city . Two buildings of equal size and similar ethnic composition were r and omized as intervention and control buildings . Pre and post intervention surveys were conducted in both buildings , measuring knowledge , attitudes and peer norms . Processes and outcomes were documented at four levels : Influenza Strategic Alliance ( macro and exo levels ) , building management ( meso level ) , building resident committee ( meso level ) and individual residents . The Influenza Strategic Alliance ( I.S.A. ) provided ongoing re sources , information and vaccine ; the building management provided economic and other in-kind re sources and supported residents to continue flu clinics in the building . The V.I.P. Resident Committee conducted flu campaigns with flu clinics in English and Spanish . The vaccination rate in the intervention building at post test exceeded the study goal of 70 % and showed a significant improvement over the control building . The intervention achieved desired outcomes at all four levels and result ed in a significant increase in influenza vaccination , and improvements in pro-vaccination knowledge , beliefs , and underst and ing of health consequences Lay Health Promoters ( LHPs ) are widely used in community health education , but their use and evaluation in occupational health has been limited to farm workers . Evaluation data were collected from 30 r and omly selected Latino poultry processing workers who had an encounter with an LHP who delivered Maria 's Story , an occupational health lesson about cumulative trauma disorders ( CTDs ) . Participants had good recall of Maria 's Story . Most participants ( n = 18 , 60 % ) could identify the primary occupational health exposure linked to CTDs , more than 50 % of participants ( n = 16 ) could recall one or more ways of preventing CTDs , and 43.3 % ( n = 13 ) described in detail recommended treatments . Nearly one-half ( n = 12 ) reported an occupational health behavior change after hearing Maria 's Story . The results of this study suggest that LHPs may be effective in promoting occupational health and reducing occupational health disparities among ethnic minorities in high-risk occupations BACKGROUND The National Cancer Institute funded an 8-year , nonr and omized demonstration project for tobacco prevention and control , the American Stop Smoking Intervention Study ( ASSIST ) . To evaluate ASSIST , we compared changes in adult smoking prevalence , per capita cigarette consumption , and tobacco control policies between the 17 ASSIST states and the 33 non-ASSIST states and the District of Columbia . METHODS The strength of tobacco control index was used to measure state-level program elements directed at tobacco control , and the initial outcomes index ( IOI ) was used to measure states ' tobacco control policy outcomes . Prevalence data were obtained from the Tobacco Use Supplement to the Current Population Survey , and consumption data were obtained from the Tobacco Institute 's bimonthly sales figures for cigarette packs moved from wholesale warehouses . Two-stage regression and mixed-effects linear modeling were used to analyze the various outcomes . Statistical analyses for testing individual regression coefficients were one-sided . RESULTS ASSIST states had a greater decrease in adult smoking prevalence than non-ASSIST states , with an adjusted difference of -0.63 % ( P = .049 ) . Per capita cigarette consumption was not statistically significantly different between ASSIST and non-ASSIST states . However , an increase in the IOI of a state from the 25th to the 75th percentile was associated with a reduction in per capita cigarette consumption by 0.57 packs per person per month . State IOI was also inversely , albeit not statistically significantly , associated with smoking prevalence ( regression coefficient = -0.11;P = .06 ) . CONCLUSIONS The reduction in adult smoking prevalence associated with ASSIST could have translated into approximately 278 700 fewer smokers nationwide if all states had implemented ASSIST . Investment in building state-level tobacco control capacity and promoting changes in tobacco control policies are effective strategies for reducing tobacco use Objective : To evaluate changes in the worksite environment in response to a multilevel intervention over a 2-year period . Methods : Worksites were recruited in the greater Seattle area , and 34 were r and omized to intervention or comparison condition . The intervention was based on the ecological model , with a framework of defined phases of intervention that included worksite-wide events implemented in partnership with employee-based advisory boards . The assessment of the worksite environment used a modification of the Checklist of Health Promotion Environments at Worksites . Subscales were developed using baseline data only . The intervention effect on different aspects of the worksite environment was estimated using logistic regression with robust estimating procedures . Results : Only changes in the physical activity and nutrition information environments were significantly associated with the intervention . Conclusions : This article provides one of the first attempts at using environmental assessment in the evaluation of worksite interventions OBJECTIVES The North Carolina WISEWOMAN project was initiated to evaluate the feasibility of exp and ing an existing cancer screening program to include a cardiovascular disease ( CVD ) screening and intervention program among low-income women . METHODS Seventeen North Carolina county health departments were design ated as minimum intervention ( MI ) , and 14 as enhanced intervention ( EI ) . The EI included three specially constructed counseling sessions spanning 6 months using a structured assessment and intervention program tailored to lower income women . RESULTS Of the 2,148 women screened , 40 % had elevated total cholesterol ( > or = 240 mg/dL ) , 39 % had low high-density lipoprotein cholesterol ( HDL-C ) levels ( < 45 mg/dL ) , and 63 % were hypertensive ( systolic blood pressure 140 and /or diastolic blood pressure > or = 90 mm Hg or on hypertensive medication ) . The majority of women ( 86 % ) had at least one of these three risk factors . Seventy-six percent were either overweight or obese . After 6 months of follow-up in the EI health departments , changes in total cholesterol levels , HDL-C levels , diastolic blood pressure , and BMI were observed ( -5.8 mg/dL , -0.9 mg/dL , -1.7 mm Hg , and -0.3 kg Output:	The findings from this descriptive review suggest that multilevel interventions have positive effects on several health behavior outcomes , including cancer prevention and screening , as well improving the quality of health-care system processes .
MS21809	*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 mechanisms underlying the skin blood flow ( SkBF ) response to local heating are complex and poorly understood . Our goal was to examine the role of axon reflexes and nitric oxide ( NO ) in the SkBF response to a local heating protocol . We performed 40 experiments following a st and ardized heating protocol with different interventions , including blockade of the axon reflex ( EMLA cream ) , antebrachial nerve blockade ( 0.5 % bupivacaine injection ) , and NO synthase ( NOS ) inhibition ( > or = 10 mM N(G)-nitro-L-arginine methyl ester ; microdialysis ) . Appropriate controls were performed to verify the efficacy of the various blocks . Values are expressed as a percentage of maximal SkBF ( SkBF(max ) ; 50 mM sodium nitroprusside ) . At the initiation of local heating , SkBF rose to an initial peak , followed by a brief nadir , and a secondary , progressive rise to a plateau . Axon reflex block decreased the initial peak from 75 + 3 to 32 + /- 2 % SkBF(max ) ( P < 0.01 vs. control ) but did not affect the plateau . NOS inhibition before and throughout local heating reduced the initial peak from 75 + /- 3 to 56 + /- 3 % SkBF(max ) ( P < 0.01 ) and the plateau from 87 + /- 4 to 40 + /- 5 % . NOS inhibition during axon reflex block did not further reduce the initial SkBF peak compared with axon reflex block alone . Antebrachial nerve block did not affect the local heating SkBF response . The primary finding of these studies is that there are at least two independent mechanisms contributing to the rise in SkBF during nonpainful local heating : a fast-responding vasodilator system mediated by the axon reflexes and a more slowly responding vasodilator system that relies on local production of NO OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity OBJECTIVE To evaluate the vasodilation induced by topical application of methyl nicotinate ( MN ) and to compare it with the vasodilatory response to acetylcholine ( ACh ) and sodium nitroprusside ( SNP ) in healthy subjects and diabetic neuropathic patients . RESEARCH DESIGN AND METHODS Ten diabetic patients with peripheral neuropathy ( DN ) and 10 age- and sex-matched healthy control subjects ( C ) were enrolled . The vasodilatory response to topical application of 1 % MN and a placebo emulsion at the forearm and dorsum of the foot skin at 5 , 15 , 30 , 60 and 120 min was measured using Laser Doppler Perfusion Imaging . The vasodilatory response to iontophoresis of 1 % ACh and 1 % SNP solutions was also evaluated . RESULTS The maximal vasodilatory response to ACh , SNP and MN was similar at the forearm and foot level in the diabetic patients . In the control group , the responses to MN , ACh and SNP were similar on the forearm but in the foot , the MN vasodilatory response was higher when compared to the ACh and SNP responses . MN-related vasodilation was present 5 min after the application , reached its peak at 15 - 30 min and declined to pre-application levels 120 min afterward . CONCLUSIONS Topical application of MN at the forearm and foot levels of diabetic neuropathic patients results in skin vasodilation that is comparable to the maximal vasodilation that can be induced by iontophoresis of ACh or SNP and lasts for less than 2 h. Further studies will be required to explore the potential of MN to increase blood flow and to prevent diabetic foot problems in clinical practice The aim of the present study was to examine the relationship among water diuresis-induced changes in renal oxygenation , endothelial function , and various metabolic parameters in type 2 diabetic patients and healthy subjects at risk of type 2 diabetes . Thirty-eight subjects with type 2 diabetes ( D : age , 54 + /- 10 years , mean + /- SD , 24 men ) and 7 healthy subjects with parental history of type 2 diabetes or with impaired glucose tolerance ( IGT ) ( relatives [ R ] : age 46 + /- 11 years , 4 men ) were included . Laser Doppler imaging scanning was used to measure vasodilatation in the forearm skin in response to iontophoresis of 1 % acetylcholine ( Ach ) and 1 % sodium nitroprusside ( SNP ) , and ultrasound was used to measure the flow-mediated dilation ( FMD ) and nitroglycerin-induced dilation ( NID ) in the brachial artery . Renal oxygenation was assessed by magnetic resonance imaging ( MRI ) before and during water diuresis . A decrease in the magnetic parameter R2 * implies an increase in oxygenation . Renal medullary oxygenation did not improve with diuresis in either group ( D : -0.5 + /- 1.9 , R : -0.4 + /- 2.1 , P = not significant [ NS ] ) . The renal cortical oxygenation showed a small , but statistically significant , improvement after diuresis in the 2 groups ( D : -0.6 + /- 1.1 , R : -0.5 + /- 0.5 , P < .05 ) . There were no correlations between the change in cortical R2 * ( R2 * post-minus R2 * prewater diuresis ) and the micro- and macrovascular reactivity . The postdiuresis renal cortical R2 * was negatively correlated with both the Ach- and SNP-induced skin vasodilation ( % change over baseline)(r = -.40 , P < .01 and r = -.39 , P < .05 , respectively ) , while no correlation existed with the FMD and NID . The baseline renal cortical oxygenation was also negatively correlated with the SNP-induced skin vasodilation ( r = -.36 , P < .05 ) and positively correlated with the fasting plasma glucose , total cholesterol , and vascular cell adhesion molecule ( VCAM ) concentrations ( r = .34 , P < .05 , r = .31 , P < .05 and r = .37 , P < .05 , respectively ) . These preliminary findings suggest an association between the kidney cortical oxygenation and the skin microvascular reactivity , glycemia , and lipidemia . Water diuresis failed to produce an improvement in renal medullary oxygenation in both patients with diabetes and subjects at risk for diabetes OBJECTIVES Capillary rarefaction is a hallmark of untreated hypertension . Recent data indicate that rarefaction may be reversed by antihypertensive treatment in nondiabetic hypertensive patients . Despite the frequent association of diabetes with hypertension , nothing is known on the capillary density of treated diabetic patients with hypertension . METHODS We enrolled 21 normotensive healthy , 25 hypertensive only , and 21 diabetic ( type 2 ) hypertensive subjects . All hypertensive patients were treated with a blocker of the renin-angiotensin system , and a majority had a home blood pressure ≤135/85 mmHg . Capillary density was assessed with videomicroscopy on dorsal finger skin and with laser Doppler imaging on forearm skin ( maximal vasodilation elicited by local heating ) . RESULTS There was no difference between any of the study groups in either dorsal finger skin capillary density ( controls 101 ± 11 capillaries/mm(2 ) , nondiabetic hypertensive 99 ± 16 , diabetic hypertensive 96 ± 18 , p > 0.5 ) or maximal blood flow in forearm skin ( controls 666 ± 114 perfusion units , nondiabetic hypertensive 612 ± 126 , diabetic hypertensive 620 ± 103 , p > 0.5 ) . CONCLUSIONS Irrespective of the presence or not of type 2 diabetes , capillary density is normal in hypertensive patients with reasonable control of blood pressure achieved with a blocker of the renin-angiotensin system OBJECTIVE To examine the effect of a 12-week daily treatment with 160 mg of valsartan , an angiotensin II receptor blocker , on the microcirculation and macrocirculation of type 2 diabetic patients ( T2DM ) and healthy subjects . METHODS This was a prospect i ve , r and omized , double-blind , placebo-controlled crossover study . Thirteen T2DM with no severe complications and 13 healthy subjects completed the trial . RESULTS Treatment with valsartan in T2DM improved the resting forearm skin blood flow and increased the resting brachial artery diameter but had no effects on arterial blood pressure , large vessel vascular reactivity , or carotid intima-media thickness . Resting skin blood flow increased by 60 % ( 2%-90 % ; median and 25th-75th percentiles ) during valsartan treatment and by only 2 % ( -22 % to 27 % ) during placebo treatment ( P < .05 ) . No changes were observed in the nondiabetic subjects . Immunostaining studies of forearm skin biopsy sample s from T2DM and healthy subjects showed that valsartan reduced poly(adenosine diphosphate-ribose ) polymerase ( PARP ) activity in 50 % ( 6/12 ) of the subjects . PARP activity remained unchanged in placebo-treated subjects ( P < .02 ) . In addition , valsartan treatment increased CD31 staining in 33 % ( 4/12 ) of the subjects , whereas no change was noted in sequential skin biopsy sample s of placebo-treated subjects ( P = .057 ) . Valsartan had no effect on the biochemical markers of endothelial cell activation and other cytokines , including CAMs , interleukin 6 , tumor necrosis factor alpha , C-reactive protein , adiponectin , and plasma activator inhibitor 1 . CONCLUSIONS Valsartan increases the resting skin blood flow in T2DM , likely through reduction of PARP activity We have investigated the effect of atorvastatin on the endothelial function of patients with diabetes and subjects at risk for type 2 diabetes in a 12-wk , prospect i ve , r and omized , placebo-controlled , double-blind clinical trial . The flow- mediated dilation ( FMD ; endothelium dependent ) and nitroglycerin-induced dilation ( endothelium independent ) in the brachial artery and the vascular reactivity at the forearm skin were measured . FMD improved in the atorvastatin-treated , at-risk subjects [ median ( 25 - 75 percentile ) , 7.2 % ( 2.9 - 9.6 % ) at exit visit vs. 6.6 % ( 2.9 - 9.5 % ) at baseline ; P < 0.05 ] . A similar improvement of FMD was found in atorvastatin-treated diabetic patients [ median ( 25 - 75 percentile ) , 5.6 ( 3.9 - 7.9 ) at exit visit vs. 4.2 ( 3.2 - 7.2 ) at baseline ; P = 0.07 ] . No changes were observed in nitroglycerin-induced dilation and the microcirculation reactivity measurements in either group . In the at-risk group , there was a decrease in the C-reactive protein [ median ( Output:	However , subgroup analysis revealed no difference between the type and duration of diabetes and other health related factors , indicating that diabetes per se causes the microvascular dysfunction . Conclusion Our meta- analysis shows that diabetes is associated with a large reduction of dermal microvascular function in diabetic patients .
MS21810	*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: Eye movements , eye blinks , cardiac signals , muscle noise , and line noise present serious problems for electroencephalographic ( EEG ) interpretation and analysis when rejecting contaminated EEG segments results in an unacceptable data loss . Many methods have been proposed to remove artifacts from EEG recordings , especially those arising from eye movements and blinks . Often regression in the time or frequency domain is performed on parallel EEG and electrooculographic ( EOG ) recordings to derive parameters characterizing the appearance and spread of EOG artifacts in the EEG channels . Because EEG and ocular activity mix bidirectionally , regressing out eye artifacts inevitably involves subtracting relevant EEG signals from each record as well . Regression methods become even more problematic when a good regressing channel is not available for each artifact source , as in the case of muscle artifacts . Use of principal component analysis ( PCA ) has been proposed to remove eye artifacts from multichannel EEG . However , PCA can not completely separate eye artifacts from brain signals , especially when they have comparable amplitudes . Here , we propose a new and generally applicable method for removing a wide variety of artifacts from EEG records based on blind source separation by independent component analysis ( ICA ) . Our results on EEG data collected from normal and autistic subjects show that ICA can effectively detect , separate , and remove contamination from a wide variety of artifactual sources in EEG records with results comparing favorably with those obtained using regression and PCA methods . ICA can also be used to analyze blink-related brain activity Driver fatigue is associated with risks of road accidents that result in injury and death . Research has been limited by several issues such as confusion over definitions , how best to measure fatigue , and the contribution of psychological factors to fatigue . This study addressed these limitations by investigating the relationship between psychological factors and fatigue . Participants were assessed and were required to perform a monotonous task till they tired . Results found few psychological factors to be related to physiological and performance decrement fatigue outcome measures . However , psychological factors were found to correlate consistently with self-reported fatigue . The results suggest that fatigue is associated with a predisposition to be anxious , depressive , less self-assured , more conscientious ( rule bound ) , less socially bold , less adaptable and low vigour . The results indicate that future research should employ a range of fatigue outcome measures in order to best underst and what factors contribute to fatigue Behavioral effects of alcohol are known to be greater when the blood alcohol is rising , known as the Mellanby effect ; however , research investigating the cortical changes during this period is scarce . The objective of this study was to investigate the effects of consumption of alcohol on cortical activity measured by the electroencephalogram ( EEG ) during the absorption or rising phase of alcohol . EEG signals were recorded using the entire 10/20 montage system . The experimental design consisted of a repeated measures r and omized crossover design in which subjects acted as their own control . This involved recording two EEG baseline measures , each of which was followed by a placebo or alcohol condition , delivered over two days for ten subjects . All subjects had a 50 % chance of receiving the alcohol first . All subjects were shown to have mean peak blood alcohol concentration ( BAC ) levels of around . 03 % . No significant differences were found between the two baselines . Significant increases in EEG magnitude occurred in the theta ( 4 - 7.75 Hz ) , alpha 1 ( 8 - 9.75 Hz ) , and beta 1 ( 13.25 - 19.75 Hz ) spectrum in the frontal EEG regions , and alpha 1 ( 8 - 9.75 Hz , ) in the central and posterior regions . No significant changes were found in the theta ( 4 - 7.75 Hz ) or beta ( 13.5 - 30 Hz ) spectrums in the central and posterior regions . There were also no significant results for alpha 2 ( 10 - 13 Hz , ) in any of the regions . These results suggest that rapid cortical changes occur within the first 35 min after alcohol consumption OBJECTIVE Cognitive behavior therapy for chronic fatigue syndrome was compared with relaxation in a r and omized controlled trial . METHODS Sixty patients with chronic fatigue syndrome were r and omly assigned to 13 sessions of either cognitive behavior therapy ( grade d activity and cognitive restructuring ) or relaxation . Outcome was evaluated by using measures of functional impairment , fatigue , mood , and global improvement . RESULTS Treatment was completed by 53 patients . Functional impairment and fatigue improved more in the group that received cognitive behavior therapy . At final follow-up , 70 % of the completers in the cognitive behavior therapy group achieved good outcomes ( substantial improvement in physical functioning ) compared with 19 % of those in the relaxation group who completed treatment . CONCLUSIONS Cognitive behavior therapy was more effective than a relaxation control in the management of patients with chronic fatigue syndrome . Improvements were sustained over 6 months of follow-up It is still controversial whether the pineal hormone melatonin can be characterized as a hypnotic . We therefore measured subjective sleepiness and waking EEG power density in the range of 0.25 - 20 Hz after a single dose of melatonin ( 5 mg ) . During an 8 h mini-constant routine protocol , melatonin administered in a double blind cross-over design to healthy young men at 1300 h or 1800 h increased subjective sleepiness , as rated half-hourly on three different scales ( Visual Analogue Scale , Akerstedt Sleepiness Symptoms Check List , Akerstedt Sleepiness Scale ) and objective fatigue as evidence d by augmented waking EEG power density in the theta/alpha range ( 5.25 - 9 Hz ) . The increase in subjective sleepiness reached significance 40 min and 90 min after melatonin administration ( at 1300 h and 1800 h , respectively ) and lasted for 3 h ( at 1300 h ) and 5 h ( at 1800 h ) . The increase in the theta/alpha frequencies of the waking EEG occurred immediately after melatonin ingestion and stayed significantly higher parallel to the higher sleepiness ratings . However , the EEG changes appeared before the subjective symptoms of sleepiness became manifest . There was a significant correlation between salivary melatonin levels and the timing of increased subjective sleepiness . Melatonin had no effects on mood The aim was to assess the suitability of EEG-based techniques to recording activity during a driving simulation task . To achieve this , an inexpensive driving simulator ( comprising a steering wheel , pedals and gear shift ) were made to function with a personal computer running ' Need for Speed ' simulation software . Simulators of this type are both inexpensive and relatively realistic . The EEG was recorded from four sites on the scalp ( P3 , P4 , F3 , F4 ) for two laps during the driving task , and during a replay task . The driving task involved participants driving a vehicle on a simulated undulating , sealed surface circuit , without any other vehicles present . Two men were participants in this experiment . Power spectra were computed and integrated to produce values of relative alpha activity for each channel and recording epoch , a time-series of alpha activity during each recorded segment . Overall values for alpha activity indicated an increase for replay compared to driving , and also driving on lap 5 compared to driving on lap 2 . The EEG changes are consistent with the notion of overall reduction of attention during the later laps and the replay task and indicate the potential of such measures for complex motor behaviour The effects of mental fatigue on planning and preparation for future actions were examined , using a task switching paradigm . Fatigue was induced by " time on task , " with subjects performing a switch task continuously for 2 hr . Subjects had to alternate between tasks on every second trial , so that a new task set was required on every second trial . Manipulations of response-stimulus intervals ( RSIs ) were used to examine whether subjects prepared themselves for the task change . Behavioral measurements , event-related potentials ( ERPs ) , and mood question naires were used to assess the effects of mental fatigue . Reaction times ( RTs ) were faster on trials in which no change in task set was required in comparison with switch trials , requiring a new task set . Long RSIs were used efficiently to prepare for the processing of subsequent stimuli . With increasing mental fatigue , preparation processes seemed to become less adequate and the number of errors increased . A clear poststimulus parietal negativity was observed on repetition trials , which reduced with time on task . This attention-related component was less pronounced in switch trials ; instead , ERPs elicited in switch trials showed a clear frontal negativity . This negativity was also diminished by time on task . ERP differences between repetition and switch trials became smaller with increasing time on task Cortical oscillations in the beta b and ( 13 - 35 Hz ) are known to be modulated by the GABAergic agonist benzodiazepine . To investigate the mechanisms generating the approximately 20-Hz oscillations in the human cortex , we administered benzodiazepines to healthy adults and monitored cortical oscillatory activity by means of magnetoencephalography . Benzodiazepine increased the power and decreased the frequency of beta oscillations over rol and ic areas . Minimum current estimates indicated the effect to take place around the h and area of the primary sensorimotor cortex . Given that previous research has identified sources of the beta rhythm in the motor cortex , our results suggest that these same motor-cortex beta sources are modulated by benzodiazepine . To explore the mechanisms underlying the increase in beta power with GABAergic inhibition , we simulated a conductance-based neuronal network comprising excitatory and inhibitory neurons . The model accounts for the increase in the beta power , the widening of the spectral peak , and the slowing down of the rhythms with benzodiazepines , implemented as an increase in GABAergic conductance . We found that an increase in IPSCs onto inhibitory neurons was more important for generating neuronal synchronization in the beta b and than an increase in IPSCs onto excitatory pyramidal cells During long and monotonous driving at night , most drivers progressively show signs of visual fatigue and loss of vigilance . Their capacity to maintain adequate driving performance usually is affected and varies with the age of the driver . The main question is to know , on one h and , if occurrence of fatigue and drowsiness is accompanied by a modification in the driving performance of the driver and , on the other h and , if this relationship partially depends on the driver 's age . Forty-six male drivers , divided into three age categories : 20 - 30 , 40 - 50 , and 60 - 70 years , performed a 350-km motorway driving session at night on a driving simulator . Driving errors were measured in terms of number of running-off-the-road incidents ( RORI ) and large speed deviations . The evolution of physiological vigilance level was evaluated using electroencephalography ( EEG ) recording . In older drivers , in comparison with young and middle-aged drivers , the degradation of driving performance was correlated to the evolution of lower frequency waking EEG ( i.e. , theta ) . Contrary to young and middle-aged drivers , the deterioration of the vigilance level attested by EEG correlated with the increase in gravity of all studied driving errors in older drivers . Thus , depending on the age category considered , only part of the driving errors would constitute a relevant indication as for the occurrence of a state of low arousal Fatigue is one of the most common psychophysiological symptoms that interact with the control mechanisms regulating task behaviour . The cortical processes involved in preparation and feedback control of voluntary movement are associated with EEG activity time-locked to movement onset : a pre-movement Movement-Related Cortical Potential ( MRCP ) is followed by a post-movement potential ( PMP ) . The aim of this study was to determine whether changes in subjective fatigue which arise in the course of a simple repetitive motor task affect cortical information processing as measured by MRCPs or PMPs . MRCPs/PMPs were recorded in 33 healthy subjects while they made 100 self-paced unilateral button presses with their left or right index finger , and then continued with the other index finger for another 100 movements . Before and after the motor tasks , subjective fatigue was assessed via question naire . ( 1 ) Subjects who reported a higher increase of fatigue when they had finished the motor tasks showed smaller ( more negative ) amplitudes of the PMP . ( 2 ) This increase of negativity was strongest during the initial part of the tasks . ( 3 ) Physical aspects of perceived fatigue had a stronger effect on PMP amplitude than cognitive aspects . Smaller amplitudes of the PMP in more fatigued subjects might be explained by reduced attention to somatosensory feedback . Adaptation of this effect may result from more automatic performance at later stages of the task when all subjects required a lower degree of attentional control . In conjunction with previous studies , effects of fatigue could be separated from habituation The present study systematic ally compared the effects of fatigue and alcohol intoxication on a range of neurobehavioural tasks . By doing so , it was possible to quantify the performance impairment associated with fatigue and express it as a blood alcohol impairment equivalent . Twenty-two healthy subjects aged 19 - 26 years participated in three counterbalanced conditions . In the sustained wakefulness condition , subjects were kept awake for 28 h. In the alcohol and placebo conditions , subjects consumed either an alcoholic or non-alcoholic beverage at 30 min intervals , until their blood alcohol concentration reached 0.10 % . In each session , performance was measured at hourly intervals using four tasks from a st and ardised computer-based test battery . Analysis indicated that the placebo beverage did not significantly effect mean relative performance . In contrast , as blood alcohol concentration increased performance on all the tasks , except for one , significantly decreased . Similarly , as hours of wakefulness increased performance levels for four of the six parameters significantly decreased . More importantly , equating the performance impairment in the two conditions indicated that , depending on the task measured , approximately 20 - 25 h of wakefulness produced performance decrements equivalent to those observed at a blood alcohol concentration ( BAC ) of 0.10 % . Overall , these results suggest that moderate levels of fatigue produce performance equivalent to or greater than those observed at levels of alcohol intoxication deemed unacceptable when driving , working and /or operating dangerous equipment Correlations between subjective Output:	The results showed that as a person fatigues , slow wave activity increased over the entire cortex , in theta and in alpha 1 and 2 b and s , while no significant changes were found in delta wave activity . Substantial increases also occurred in fast wave activity , though mostly in frontal sites . The results suggest that as a person fatigues , the brain loses capacity and slows its activity , and that attempts to maintain vigilance levels lead to increased beta activity
MS21811	*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 double-blind , r and omized crossover study investigated the effects of 6 weeks of treatment with prescription omega-3-acid ethyl esters ( POM3 , 4 g/day ) versus placebo ( soy oil ) on low-density lipoprotein cholesterol ( LDL-C ) and other aspects of the fasting lipid profile in 31 men and women with primary , isolated hypercholesterolemia ( LDL-C 130 - 220 mg/dL and triglycerides less than 150 mg/dL while free of lipid-altering therapies ) . Mean ± st and ard error of the mean baseline concentrations of total cholesterol , LDL-C , high-density lipoprotein cholesterol ( HDL-C ) , very-low-density lipoprotein cholesterol , and triglycerides were 229 ± 3 , 146 ± 3 , 60 ± 2 , 23 ± 2 , and 113 ± 8 mg/dL , respectively . POM3 produced a modest increase from baseline in LDL-C ( 3.4 % ) versus the placebo response ( -0.7 % , P = 0.010 ) . Significant changes ( P < 0.05 ) for POM3 ( placebo-corrected ) were observed for very-low-density lipoprotein cholesterol ( -18.8 % ) , triglycerides ( -18.7 % ) , and HDL-C ( 3.3 % ) . Nuclear magnetic resonance-determined very-low-density lipoprotein particle concentration and size and HDL particle concentration decreased significantly more with POM3 versus placebo , whereas LDL and HDL particle sizes increased significantly more with POM3 versus placebo . Total cholesterol , non-HDL-C , apolipoproteins A1 and B , and LDL particle concentration responses did not differ between treatments . These results did not confirm the hypothesis that POM3 treatment would lower LDL-C in primary , isolated hypercholesterolemia . Effects on other variables were consistent with prior results in mixed dyslipidemia High doses of n-3 PUFA found in fish oils can reduce the circulating concentration of triacylglycerol ( TG ) , which may contribute to the positive impact of these fatty acids on the risk of CVD . The present study aim ed to establish the differential impact of EPA and docosahexaenoic ( DHA ) on plasma lipids and apo in adults . Forty-two normolipidaemic adult subjects completed a double-blind placebo controlled parallel study , receiving an EPA-rich oil ( 4.8 g EPA/d ) , DHA-rich oil ( 4.9 g DHA/d ) or olive oil as control , for a period of 4 weeks . No effects of treatment on total cholesterol , LDL-cholesterol or HDL-cholesterol were evident . There was a significant 22 % reduction in TG level relative to the control value following the DHA treatment ( P=0.032 ) , with the 15 % decrease in the EPA group failing to reach significance ( P=0.258 ) . There were no significant inter-group differences in response to treatment for plasma apoA1 , -C3 or -E levels , although a significant 15 % within-group increase in apoE was evident in the EPA ( P=0.006 ) and DHA ( P=0.003 ) groups . In addition , a within-group decrease in the apoA1:HDL-cholesterol ratio was observed in the DHA group , suggesting a positive impact of DHA on HDL particle size . The DHA intervention result ed in a significant increase in the proportion of EPA P=0.000 and DHA P=0.000 in plasma phospholipids , whilst significant increases in EPA P=0.000 and docosapentaenoic acid P=0.002 , but not DHA P=0.193 , were evident following EPA supplementation ( P<0.05 ) . Our present results indicate that DHA may be more efficacious than EPA in improving the plasma lipid profile CONTEXT High-density lipoprotein ( HDL ) cholesterol is an inverse predictor of coronary atherosclerotic disease . Preliminary data have suggested that HDL infusions can induce atherosclerosis regression . OBJECTIVE To investigate the effects of reconstituted HDL on plaque burden as assessed by intravascular ultrasound ( IVUS ) . DESIGN AND SETTING A r and omized placebo-controlled trial was conducted at 17 centers in Canada . Intravascular ultrasound was performed to assess coronary atheroma at baseline and 2 to 3 weeks after the last study infusion . PATIENTS Between July 2005 and October 2006 , 183 patients had a baseline IVUS examination and of those , 145 had evaluable serial IVUS examinations after 6 weeks . INTERVENTION Sixty patients were r and omly assigned to receive 4 weekly infusions of placebo ( saline ) , 111 to receive 40 mg/kg of reconstituted HDL ( CSL-111 ) ; and 12 to receive 80 mg/kg of CSL-111 . MAIN OUTCOME MEASURES The primary efficacy parameter was the percentage change in atheroma volume . Nominal changes in plaque volume and plaque characterization index on IVUS and coronary score on quantitative coronary angiography were also prespecified end points . RESULTS The higher-dosage CSL-111 treatment group was discontinued early because of liver function test abnormalities . The percentage change in atheroma volume was -3.4 % with CSL-111 and -1.6 % for placebo ( P = .48 between groups , P<.001 vs baseline for CSL-111 ) . The nominal change in plaque volume was -5.3 mm3 with CSL-111 and -2.3 mm3 with placebo ( P = .39 between groups , P<.001 vs baseline for CSL-111 ) . The mean changes in plaque characterization index on IVUS ( -0.0097 for CSL-111 and 0.0128 with placebo ) and mean changes in coronary score ( -0.039 mm for CSL-111 and -0.071 mm with placebo ) on quantitative coronary angiography were significantly different between groups ( P = .01 and P = .03 , respectively ) . Administration of CSL-111 40 mg/kg was associated with mild , self-limiting transaminase elevation but was clinical ly well tolerated . CONCLUSIONS Short-term infusions of reconstituted HDL result ed in no significant reductions in percentage change in atheroma volume or nominal change in plaque volume compared with placebo but did result in statistically significant improvement in the plaque characterization index and coronary score on quantitative coronary angiography . Elevation of HDL remains a valid target in vascular disease and further studies of HDL infusions , including trials with clinical end points , appear warranted . TRIAL REGISTRATION clinical trials.gov Identifier : In a r and omized , cross-over feeding trial involving 10 men with polygenic hypercholesterolemia , a control , Mediterranean-type cholesterol-lowering diet , and a diet of similar composition in which walnuts replaced approximately 35 % of energy from unsaturated fat , were given for 6 weeks each . Compared with the control diet , the walnut diet reduced serum total and LDL cholesterol by 4.2 % ( P = 0.176 ) , and 6.0 % ( P = 0.087 ) , respectively . No changes were observed in HDL cholesterol , triglycerides , and apolipoprotein A-I levels or in the relative proportion of protein , triglycerides , phospholipids , and cholesteryl esters in LDL particles . The apolipoprotein B level declined in parallel with LDL cholesterol ( 6.0 % reduction ) . Whole LDL , particularly the triglyceride fraction , was enriched in polyunsaturated fatty acids from walnuts ( linoleic and alpha-linolenic acids ) . In comparison with LDL obtained during the control diet , LDL obtained during the walnut diet showed a 50 % increase in association rates to the LDL receptor in human hepatoma HepG2 cells . LDL uptake by HepG2 cells was correlated with alpha-linolenic acid content of the triglyceride plus cholesteryl ester fractions of LDL particles ( r(2 ) = 0.42 , P < 0.05 ) . Changes in the quantity and quality of LDL lipid fatty acids after a walnut-enriched diet facilitate receptor-mediated LDL clearance and may contribute to the cholesterol-lowering effect of walnut consumption Clinical trials have shown that soya protein reduces the concentrations of some atherogenic lipids in subjects with normal renal function . The present study examined the effects of soya protein on serum lipid concentrations and lipoprotein metabolism in patients on hypercholesterolaemic haemodialysis . Twenty-six hypercholesterolaemic ( total cholesterol > or = 6.21 mmol/l ) patients on haemodialysis were studied in a r and omized , double-blind , placebo-controlled clinical trial . After a 4-week run-in phase , the subjects were r and omly assigned to two groups . Isolated soya protein or milk protein 30 g was consumed daily as a beverage at breakfast or post-dialysis for 12 weeks . Soya protein substitution result ed in significant reductions in total cholesterol ( 17.2 ( sd 8.9 ) % ) , LDL-cholesterol ( 15.3 ( sd 12.5 ) % ) , apo B ( 14.6 ( sd 12.1 ) % ) and insulin ( 23.8 ( sd 18.7 ) % ) concentrations . There were no significant changes in HDL-cholesterol or apo A-I. These results indicate that replacing part of the daily protein intake with soya protein has a beneficial effect on atherogenic lipids and favourably affects lipoprotein metabolism in hypercholesterolaemic patients undergoing haemodialysis BACKGROUND In observational analyses , higher levels of high-density lipoprotein ( HDL ) cholesterol have been associated with a lower risk of coronary heart disease events . However , whether raising HDL cholesterol levels therapeutically reduces cardiovascular risk remains uncertain . Inhibition of cholesteryl ester transfer protein ( CETP ) raises HDL cholesterol levels and might therefore improve cardiovascular outcomes . METHODS We r and omly assigned 15,871 patients who had had a recent acute coronary syndrome to receive the CETP inhibitor dalcetrapib , at a dose of 600 mg daily , or placebo , in addition to the best available evidence -based care . The primary efficacy end point was a composite of death from coronary heart disease , nonfatal myocardial infa rct ion , ischemic stroke , unstable angina , or cardiac arrest with resuscitation . RESULTS At the time of r and omization , the mean HDL cholesterol level was 42 mg per deciliter ( 1.1 mmol per liter ) , and the mean low-density lipoprotein ( LDL ) cholesterol level was 76 mg per deciliter ( 2.0 mmol per liter ) . Over the course of the trial , HDL cholesterol levels increased from baseline by 4 to 11 % in the placebo group and by 31 to 40 % in the dalcetrapib group . Dalcetrapib had a minimal effect on LDL cholesterol levels . Patients were followed for a median of 31 months . At a prespecified interim analysis that included 1135 primary end-point events ( 71 % of the projected total number ) , the independent data and safety monitoring board recommended termination of the trial for futility . As compared with placebo , dalcetrapib did not alter the risk of the primary end point ( cumulative event rate , 8.0 % and 8.3 % , respectively ; hazard ratio with dalcetrapib , 1.04 ; 95 % confidence interval , 0.93 to 1.16 ; P=0.52 ) and did not have a significant effect on any component of the primary end point or total mortality . The median C-reactive protein level was 0.2 mg per liter higher and the mean systolic blood pressure was 0.6 mm Hg higher with dalcetrapib as compared with placebo ( P<0.001 for both comparisons ) . CONCLUSIONS In patients who had had a recent acute coronary syndrome , dalcetrapib increased HDL cholesterol levels but did not reduce the risk of recurrent cardiovascular events . ( Funded by F. Hoffmann-La Roche ; dal- OUTCOMES Clinical Trials.gov number , NCT00658515 . ) Objective —To determine mechanisms contributing to decreased high-density lipoprotein cholesterol ( HDL-C ) and increased low-density lipoprotein cholesterol ( LDL-C ) concentrations associated with hydrogenated fat intake , kinetic studies of apoA-I , apoB-100 , and apoB-48 were conducted using stable isotopes . Methods and Results —Eight postmenopausal hypercholesterolemic women were provided in r and om order with 3 diets for 5-week periods . Two-thirds of the fat was soybean oil ( unsaturated fat ) , stick margarine ( hydrogenated fat ) , or butter ( saturated fat ) . Total and LDL-C levels were highest after the saturated diet ( P < 0.05 ; saturated versus unsaturated ) whereas HD Output:	We conclude that both dietary components and pharmacological approaches can be used to increase apoA-I concentrations or functionality . For the dietary components in particular , more knowledge about the underlying mechanisms is necessary , as increasing apoA-I per se does not necessarily translate into a reduced CHD risk
MS21812	*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: AIM The therapy of chronic hepatitis C genotype 4 ( HCV-4 ) has not been optimized yet . This r and omized , prospect i ve , parallel-group clinical trial compared the efficacy and safety of pegylated interferon α-2a ( PEG-IFN α-2a ) plus ribavirin and PEG-IFN α-2b plus ribavirin and assessed the health-related quality of life ( HRQOL ) in patients with chronic HCV-4 . METHODS Eligible patients with proven chronic HCV-4 were r and omized to receive either a weekly dose of PEG-IFN α-2a ( 180 μg ) or PEG-IFN α-2b ( 1.5 μg/kg ) and a daily dose of ribavirin ( 1000 - 1200 mg ) for 48 weeks with 24 weeks post-treatment follow-up . The primary end point was sustained virological response ( SVR ) defined by undetectable HCV RNA 24 weeks after treatment . The Short form-36 Health Survey version 2 ( SF-36v2 ) and the Chronic Liver Disease question naires ( CLDQ ) were assessed before , during and after therapy . RESULTS The overall SVR rate of the entire cohort was 59.9 % . The SVR rates were significantly higher in patients treated with PEG-IFN α-2a and ribavirin ( Group A ; n=109 ) compared with those treated with PEG-IFN α-2b and ribavirin ( Group B ; n=108 , 70.6 vs. 54.6 % , respectively ; P=0.017 ) . The relapse rates were 5.1 % for PEG-IFN α-2a and 15.7 % for PEG-IFN α-2b ( P=0.0019 ) . The SF-36v2 and CLDQ were low during therapy and improved significantly after therapy successful therapy . CONCLUSION Pegylated interferon α-2a plus ribavirin was significantly more effective than PEG-IFN α-2b and ribavirin therapy in the treatment of chronic HCV-4 patients . The tolerability and adverse events were comparable between the two regimens . The HRQOL improved significantly after successful PEG-IFN α-2a plus ribavirin therapy BACKGROUND / AIMS As evidence accumulates relating to mother-to-child ( vertical ) transmission of hepatitis C virus ( HCV ) , it is timely to draw up guidelines for the clinical management of HCV infected pregnant women and their children . METHODS A review of evidence from the European Paediatric HCV Network ( EPHN ) prospect i ve study of HCV infected women and their children and other published studies . Meeting of EPHN clinical experts to reach a consensus on recommendations for management . Each recommendation was grade d according to the level of evidence . RESULTS / CONCLUSIONS Although several risk factors for mother-to-child transmission have been identified , none are modifiable and there are currently no interventions available to prevent vertical transmission of HCV . Data on timing of loss of maternal antibodies and reliability of diagnostic tests inform the optimum follow-up schedule for confirmation or exclusion of infection in children born to HCV infected women . Based on the current evidence , routine antenatal screening for HCV should not be introduced and neither elective caesarean section nor avoidance of breastfeeding should be recommended to HCV infected women to prevent mother-to-child transmission of HCV . HCV/HIV co-infected women should follow existing HIV guidelines Previous trials investigating the efficacy of treatment duration s shorter than the st and ard of 24 weeks for chronic hepatitis C virus ( HCV ) genotype 2/3 infections have yielded discordant results . The aims of this investigator‐initiated phase III study were to compare the efficacy of 12 or 24 weeks of treatment and to identify patients suitable for short‐term therapy . Three hundred eighty‐two genotype 2/3–infected patients [ intention‐to‐treat ( ITT ) population ] at 31 centers in Denmark , Finl and , Norway , and Sweden were r and omized to 12 or 24 weeks of peginterferon α‐2a ( 180 μg/week ) plus ribavirin ( 800 mg/day ) . Twelve weeks of therapy was inferior to 24 weeks in the ITT population ( sustained viral response [ SVR ] rates : 59 % versus 78 % , P < 0.0001 ) and in the subgroups of patients infected with genotype 2 ( 56 % versus 82 % , P = 0.006 ) or 3 ( 58 % versus 78 % , P = 0.0015 ) . These differences were observed regardless of the fibrosis stage . Age and HCV‐RNA levels on days 7 and 29 were independent predictors of SVR . Short‐term treatment was useful in patients < 40 years old , especially if HCV‐RNA was undetectable on day 29 , and also in patients ≥ 40 years old , provided that HCV‐RNA was below 1000 IU/mL on day 7 in addition to being undetectable on day 29 . If neither of these two criteria were met for patients ≥ 40 years old , 24 weeks of therapy was superior ( P < 0.0001 ) . Conclusion : Peginterferon/ribavirin treatment for 12 weeks in HCV genotype 2/3 infection is overall inferior to 24 weeks of treatment but may be useful in some patients with a rapid initial clearance of virus . ( HEPATOLOGY 2008 . BACKGROUND & AIMS Ribavirin ( RBV ) combined with either pegylated interferon ( PegIFN ) alpha2a or PegIFNalpha2b is the st and ard of care for chronic hepatitis C virus ( HCV ) infection . Due to the lack of head-to-head studies , the 2 PegIFNs have not been directly compared . The endpoints of our study were safety and antiviral efficacy of the 2 regimens . METHODS Treatment-naïve patients with chronic hepatitis C were r and omly ( 1:1 ) assigned after stratification for HCV genotype to receive either 1.5 mcg/Kg/week PegIFNalpha2b plus RBV 800 - 1200 mg/day or 180 mcg/week PegIFNalpha2a plus RBV 800 - 1200 mg/day for 24 or 48 weeks according to HCV genotype . The study was powered to detect a difference of at least 10 % in safety and efficacy of the 2 regimens . RESULTS The 212 patients on PegIFNalpha2a and the 219 patients on PegIFNalpha2b had similar baseline characteristics , including cirrhosis ( 20 % vs 18 % , respectively ) . By intention to treat , the 2 groups showed similar rates of treatment-related serious adverse events ( 1 % vs 1 % , respectively ) and drop out rates for adverse effects ( 7 % vs 6 % , respectively ) . Overall , sustained virologic response ( SVR ) rate was higher in PegIFNalpha2a than in PegIFNalpha2b patients ( 66 % vs 54 % , respectively , P = .02 ) , being 48 % vs 32 % in the 222 HCV-1 and -4 patients ( P = .04 ) , and 96 % vs 82 % , respectively , in the 143 HCV-2 patients ( P = .01 ) . PegIFNalpha2a independently predicted SVR in the logistic regression analysis ( odds ratio , 1.88 ; 95 % confidence interval : 1.20 - 2.96 ) . CONCLUSIONS Although the 2 regimens showed a similar safety profile , the PegIFNalpha2a-based treatment yielded significantly more SVR than PegIFNalpha2b BACKGROUND & AIMS There is increasing interest in identifying patients with chronic hepatitis C genotype 2 or 3 infection in whom it is possible to lower the burden of therapy while retaining high levels of efficacy . METHODS Treatment-naive patients with chronic hepatitis C genotype 2/3 infection were r and omized to receive peginterferon alfa-2b ( 1.5μg/kg/wk ) for 24weeks ( group A ) ; peginterferon alfa-2b ( 1.0μg/kg/wk ) for 24weeks ( group B ) ; or peginterferon alfa-2b ( 1.5μg/kg/wk ) for 16weeks ( group C ) , each in combination with weight-based ribavirin ( 800 - 1200mg/d ) . The study population comprised two cohorts : the Hep-Net cohort enrolled in Germany and an International cohort enrolled at study sites throughout Europe and Asia . The primary end point was sustained virological response ( SVR ) . RESULTS The study included 682 patients ; 80.2 % had genotype 3 infection . In the intent-to-treat population , SVR rates were 66.5 % , 64.3 % , and 56.6 % in groups A , B , and C , and were similar in Asian and white patients . Treatment differences ( A vs. B and A vs. C ) failed to reach the predefined margin for noninferiority of -10 % ; and thus groups B and C failed to show noninferiority relative to group A. Among patients with undetectable HCV RNA at week 4 , SVR rates were 75.3 % , 75.9 % , and 72.4 % , respectively . Relapse rates were 17.8 % , 16.3 % , and 29.3 % , respectively . Treatment-emergent serious adverse events were highest in group A and lowest in group C , and adverse events leading to discontinuation were similar across treatment arms . CONCLUSIONS For patients with chronic hepatitis C genotype 2/3 infection , 24weeks of peginterferon alfa-2b ( 1.5μg/kg/wk ) plus weight-based ribavirin remains a st and ard-of-care therapy ; however , treatment for 16weeks may be considered for patients with undetectable HCV RNA at week 4 of the treatment BACKGROUND Patients with chronic hepatitis C virus ( HCV ) infection who have not had a response to therapy with peginterferon and ribavirin may benefit from the addition of multiple direct-acting antiviral agents to their treatment regimen . METHODS This open-label , phase 2a study included an exploratory cohort of 21 patients with chronic HCV genotype 1 infection who had not had a response to previous therapy ( i.e. , had not had ≥2 log(10 ) decline in HCV RNA after ≥12 weeks of treatment with peginterferon and ribavirin ) . We r and omly assigned patients to receive the NS5A replication complex inhibitor daclatasvir ( 60 mg once daily ) and the NS3 protease inhibitor asunaprevir ( 600 mg twice daily ) alone ( group A , 11 patients ) or in combination with peginterferon alfa-2a and ribavirin ( group B , 10 patients ) for 24 weeks . The primary end point was the percentage of patients with a sustained virologic response 12 weeks after the end of the treatment period . RESULTS A total of 4 patients in group A ( 36 % ; 2 of 9 with HCV genotype 1a and 2 of 2 with genotype 1b ) had a sustained virologic response at 12 weeks after treatment and also at 24 weeks after treatment .. Six patients ( all with HCV genotype 1a ) had viral breakthrough while receiving therapy , and resistance mutations to both antiviral agents were found in all cases ; 1 patient had a viral response at the end of treatment but had a relapse after the treatment period . All 10 patients in group B had a sustained virologic response at 12 weeks after treatment , and 9 had a sustained virologic response at 24 weeks after treatment . Diarrhea was the most common adverse event in both groups . Six patients had transient elevations of alanine aminotransferase levels to more than 3 times the upper limit of the normal range . CONCLUSIONS This preliminary study involving patients with HCV genotype 1 infection who had not had a response to prior therapy showed that a sustained virologic response can be achieved with two direct-acting antiviral agents only . In addition , a high rate of sustained virologic response was achieved when the two direct-acting antiviral agents were combined with peginterferon alfa-2a and ribavirin . ( Funded by Bristol-Myers Squibb ; Clinical Trials.gov number , NCT01012895 . ) AIM To evaluate the significance of induction with high doses of pegylated interferon -2b ( Peg-IFNalpha-2b ) and the predictability of sustained virologic response ( SVR ) in naïve patients with chronic hepatitis C. METHODS 188 consecutive naïve patients with chronic hepatitis C were enrolled in a r and omised controlled clinical trial . Patients were r and omised to receive either Peg-IFN -2b 3.0 mcg/kg QW x 12 weeks followed by 1.5 mcg/kg QW x 36 weeks plus 800 - 1200 mg ribavirin ( Arm A ) or Peg-IFNalpha-2b 1.5 mcg/kg QW x 48 weeks plus 800 - 1200 mg ribavirin ( Arm B ) . HCV-RNA was obtained at Output:	Compared with dual therapy , boceprevir triple therapy increased risk for hematologic adverse events and telaprevir triple therapy increased risk for anemia and rash . A large well- design ed cohort study and 18 smaller cohort studies found that an SVR after antiviral therapy was associated with lower risk for all-cause mortality than was no SVR . SVR rates for genotype 1 infection are higher with triple therapy that includes a protease inhibitor than with st and ard dual therapy . An SVR after antiviral therapy appears associated with improved clinical outcomes .
MS21813	*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 AIDS Clinical Trials Group protocol 076 zidovudine prophylaxis regimen for HIV-1-infected pregnant women and their babies has been associated with a significant decrease in vertical HIV-1 transmission in non-breastfeeding women in developed countries . We compared the safety and efficacy of short-course nevirapine or zidovudine during labour and the first week of life . METHODS From November , 1997 , to April , 1999 , we enrolled 626 HIV-1-infected pregnant women at Mulago Hospital in Kampala , Ug and a. We r and omly assigned mothers nevirapine 200 mg orally at onset of labour and 2 mg/kg to babies within 72 h of birth , or zidovudine 600 mg orally to the mother at onset of labour and 300 mg every 3 h until delivery , and 4 mg/kg orally twice daily to babies for 7 days after birth . We tested babies for HIV-1 infection at birth , 6 - 8 weeks , and 14 - 16 weeks by HIV-1 RNA PCR . We assessed HIV-1 transmission and HIV-1-free survival with Kaplan-Meier analysis . FINDINGS Nearly all babies ( 98.8 % ) were breastfed , and 95.6 % were still breastfeeding at age 14 - 16 weeks . The estimated risks of HIV-1 transmission in the zidovudine and nevirapine groups were : 10.4 % and 8.2 % at birth ( p=0.354 ) ; 21.3 % and 11.9 % by age 6 - 8 weeks ( p=0.0027 ) ; and 25.1 % and 13.1 % by age 14 - 16 weeks ( p=0.0006 ) . The efficacy of nevirapine compared with zidovudine was 47 % ( 95 % CI 20 - 64 ) up to age 14 - 16 weeks . The two regimens were well tolerated and adverse events were similar in the two groups . INTERPRETATION Nevirapine lowered the risk of HIV-1 transmission during the first 14 - 16 weeks of life by nearly 50 % in a breastfeeding population . This simple and inexpensive regimen could decrease mother-to-child HIV-1 transmission in less-developed countries The safety , toxicity , and pharmacokinetics of intrapartum and early newborn nevirapine were evaluated in 17 human immunodeficiency virus type 1-infected women in labor and their newborns . No adverse effects of nevirapine were noted in any study mothers or infants . Following maternal dosing with 200 mg during labor , concentrations exceeding 100 ng/mL ( 10 times the in vitro IC50 ) were achieved in the newborns . Nevirapine elimination was prolonged in both mothers and infants , with median half-lives ranging from 36.8 to 65.7 h. Administration of 200 mg orally to the mothers in labor and of a single 2-mg/kg oral dose to the infants at 48 - 72 h after birth maintained serum concentrations in the infants > 100 ng/mL through 7 days of life BACKGROUND Perinatal transmission of human immunodeficiency virus ( HIV ) type 1 contributes significantly to infant mortality . Exposure in the birth canal may account for some transmission . We examined the efficacy of a birth canal washing procedure in reducing perinatal transmission in Malawi . METHODS The infection status of infants of 3327 control women ( conventional delivery procedures ) was compared with that of 3637 infants of intervention-delivered women . The infants ' HIV status was determined by polymerase chain reaction on dried blood spots collected at 6 and 12 weeks of age . The intervention consisted of manual cleansing of the birth canal with a cotton pad soaked in 0.25 % chlorhexidine , which was done on admission in labour and every 4 h until delivery . FINDINGS No adverse reactions to the intervention procedure were seen . 2094 ( 30 % ) of the enrolled women were HIV-infected , and 59 % of their infants were seen in follow-up . Among 982 vaginal vertex singleton deliveries to HIV-infected women , 269 ( 27 % ) infants were infected . The intervention had no significant impact on HIV transmission rates ( 27 % in 505 intervention women compared with 28 % in 477 control women ) , except when membranes were ruptured more than 4 h before delivery ( transmission 25 % in the intervention group vs 39 % in the control group ) . INTERPRETATION If birth canal exposure is an important risk factor , different or additional methods to reduce the risk of perinatal HIV transmission should be tested . Alternatively , perhaps birth canal exposure is not a major contributor to perinatal infection risk BACKGROUND In HIV-1-infected women , poor micronutrient status has been associated with faster progression of HIV-1 disease and adverse birth outcomes . We assessed the effects of vitamin A and multivitamins on birth outcomes in such women . METHODS In Tanzania , 1075 HIV-1-infected pregnant women at between 12 and 27 weeks ' gestation received placebo ( n=267 ) , vitamin A ( n=269 ) , multivitamins excluding vitamin A ( n=269 ) , or multivitamins including vitamin A ( n=270 ) in a r and omised , double-blind , placebo-controlled trial with a 2x2 factorial design . We measured the effects of multivitamins and vitamin A on birth outcomes and counts of T lymphocyte subsets . We did analyses by intention to treat . RESULTS 30 fetal deaths occurred among women assigned multivitamins compared with 49 among those not on multivitamins ( relative risk 0.61 [ 95 % CI 0.39 - 0.94 ] p=0.02 ) . Multivitamin supplementation decreased the risk of low birthweight ( < 2500 g ) by 44 % ( 0.56 [ 0.38 - 0.82 ] p=0.003 ) , severe preterm birth ( < 34 weeks of gestation ) by 39 % ( 0.61 [ 0.38 - 0.96 ] p=0.03 ) , and small size for gestational age at birth by 43 % ( 0.57 [ 0.39 - 0.82 ] p=0.002 ) . Vitamin A supplementation had no significant effect on these variables . Multivitamins , but not vitamin A , result ed in a significant increase in CD4 , CD8 , and CD3 counts . INTERPRETATION Multivitamin supplementation is a low-cost way of substantially decreasing adverse pregnancy outcomes and increasing T-cell counts in HIV-1-infected women . The clinical relevance of our findings for vertical transmission and clinical progression of HIV-1 disease is yet to be ascertained BACKGROUND AND METHODS Maternal-infant transmission is the primary means by which young children become infected with human immunodeficiency virus type 1 ( HIV ) . We conducted a r and omized , double-blind , placebo-controlled trial of the efficacy and safety of zidovudine in reducing the risk of maternal-infant HIV transmission . HIV-infected pregnant women ( 14 to 34 weeks ' gestation ) with CD4 + T-lymphocyte counts above 200 cells per cubic millimeter who had not received antiretroviral therapy during the current pregnancy were enrolled . The zidovudine regimen included antepartum zidovudine ( 100 mg orally five times daily ) , intrapartum zidovudine ( 2 mg per kilogram of body weight given intravenously over one hour , then 1 mg per kilogram per hour until delivery ) , and zidovudine for the newborn ( 2 mg per kilogram orally every six hours for six weeks ) . Infants with at least one positive HIV culture of peripheral-blood mononuclear cells were classified as HIV-infected . RESULTS From April 1991 through December 20 , 1993 , the cutoff date for the first interim analysis of efficacy , 477 pregnant women were enrolled ; during the study period , 409 gave birth to 415 live-born infants . HIV-infection status was known for 363 births ( 180 in the zidovudine group and 183 in the placebo group ) . Thirteen infants in the zidovudine group and 40 in the placebo group were HIV-infected . The proportions infected at 18 months , as estimated by the Kaplan-Meier method , were 8.3 percent ( 95 percent confidence interval , 3.9 to 12.8 percent ) in the zidovudine group and 25.5 percent ( 95 percent confidence interval , 18.4 to 32.5 percent ) in the placebo group . This corresponds to a 67.5 percent ( 95 percent confidence interval , 40.7 to 82.1 percent ) relative reduction in the risk of HIV transmission ( Z = 4.03 , P = 0.00006 ) . Minimal short-term toxic effects were observed . The level of hemoglobin at birth in the infants in the zidovudine group was significantly lower than that in the infants in the placebo group . By 12 weeks of age , hemoglobin values in the two groups were similar . CONCLUSIONS In pregnant women with mildly symptomatic HIV disease and no prior treatment with antiretroviral drugs during the pregnancy , a regimen consisting of zidovudine given ante partum and intra partum to the mother and to the newborn for six weeks reduced the risk of maternal-infant HIV transmission by approximately two thirds We conducted a double-blind , placebo-controlled trial of the efficacy of oral azidothymidine ( AZT ) in 282 patients with the acquired immunodeficiency syndrome ( AIDS ) manifested by Pneumocystis carinii pneumonia alone , or with advanced AIDS-related complex . The subjects were stratified according to numbers of T cells with CD4 surface markers and were r and omly assigned to receive either 250 mg of AZT or placebo by mouth every four hours for a total of 24 weeks . One hundred forty-five subjects received AZT , and 137 received placebo . When the study was terminated , 27 subjects had completed 24 weeks of the study , 152 had completed 16 weeks , and the remainder had completed at least 8 weeks . Nineteen placebo recipients and 1 AZT recipient died during the study ( P less than 0.001 ) . Opportunistic infections developed in 45 subjects receiving placebo , as compared with 24 receiving AZT . The base-line Karnofsky performance score and weight increased significantly among AZT recipients ( P less than 0.001 ) . A statistically significant increase in the number of CD4 cells was noted in subjects receiving AZT ( P less than 0.001 ) . After 12 weeks , the number of CD4 cells declined to pretreatment values among AZT recipients with AIDS but not amonG AZT recipients with AIDS-related complex . Skin-test anergy was partially reversed in 29 percent of subjects receiving AZT , as compared with 9 percent of those receiving placebo ( P less than 0.001 ) . These data demonstrate that AZT administration can decrease mortality and the frequency of opportunistic infections in a selected group of subjects with AIDS or AIDS-related complex , at least over the 8 to 24 weeks of observation in this study The goal of this exercise was to provide estimates of the mother-to-child transmission rate ( TR ) of human immunodeficiency virus type 1 ( HIV-1 ) , calculated according to st and ardized methods . Prospect i ve cohort studies in Africa ( 8) , the Caribbean ( 1 ) , Europe ( 3 ) , and the U.S.A. ( 1 ) observed from birth children born to women known to be HIV infected at the time of delivery . TRs were calculated and compared by investigators during a meeting in Ghent ( Belgium ) in September 1993 according to agreed methodology . TRs were calculated following the direct and the indirect methods developed in 1992 by the Ghent Working Group . The direct method uses a classification of children born to HIV-seropositive mothers according to their probable HIV infection status at 15 months of age or before , if they die or are lost to follow-up . Minimum , intermediate , and maximum estimates of TR are computed depending on how children classified as indeterminate are counted . The indirect method is applied for studies with a comparison cohort of children born to HIV-seronegative mothers . TRs in developed countries ranged from 14 to 25 % with the direct method ( intermediate estimate ) . In the developing world , they ranged from 13 to 42 % with the direct method , from 21 to 43 % with the indirect method , and most of the studies reported a TR in the range of 25 to 30 % . With use of a st and ardized methodology , the overall TR of HIV-1 tends to be higher in Africa than in Europe or the U.S.A. ( ABSTRACT TRUNCATED AT 250 WORDS CONTEXT With the success of zidovudine chemoprophylaxis for prevention of perinatal transmission of the human immunodeficiency virus ( HIV ) , an increasing number of Output:	There is no evidence that ' long course therapy ' is superior to ' short course therapy ' . REVIEW ER 'S CONCLUSIONS Zidovudine , nevirapine and delivery by elective caesarean section appear to be very effective in decreasing the risk of mother-to-child transmission of HIV infection
MS21814	*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 natural history of atherosclerosis progression following revascularization procedures ( PTCA or CABG ) limits the long-term benefits of these procedures and requires continuation of risk management . MATERIAL / METHODS Of 392 patients with multivessel disease r and omized to an initial strategy of PTCA or CABG in the Emory Angioplasty Versus Surgery Trial ( EAST ) , 298 patients ( 152 PTCA and 146 CABG ) completed 3-year angiographic follow-up . Native coronary artery disease progression was defined as lesions with < 50 % diameter stenosis ( % S ) at baseline , measured by QCA , that increased at least 10%S to become > or=50%S during the 3-year follow-up . Major ischemic events ( new Q-wave myocardial infa rct ion , a large reversible thallium defect or additional revascularization procedures ) attributed to these new lesions were determined based on the ECG ischemic changes and /or the details of the coronary anatomy . RESULTS Of 298 patients , 53 ( 18 % ) ( 15 % of PTCA and 21 % of CABG ) developed at least one significant new native coronary artery lesion . Of 136 patients with events , 19 ( 14 % ) had such events due to progression . In multivariate analysis , native coronary disease progression was independently correlated with hypertension ( OR=2.4 , p=0.03 ) , ST segment depression = 1 mm on baseline ETT ( OR=2.7 , p=0.01 ) , and percent of small LDL particles ( LDL IIIa-IVb ) ( OR=1.2 for every 5 % increase , p=0.01 ) . CONCLUSIONS In EAST , the native CAD progression accounted for one in seven major ischemic episodes over a 3-year follow-up . Patients with metabolic atherogenic risk profiles were more likely to have disease progression . These findings indicate the importance of more aggressive risk factor modification following revascularization AIMS To evaluate the association of low-density lipoprotein cholesterol ( LDL-C ) levels in small and large LDL particles with risk of incident coronary heart disease ( CHD ) . METHODS AND RESULTS We performed a prospect i ve case-control study nested in the EPIC-Norfolk cohort . Cases were apparently healthy men and women aged 45 - 79 years who developed fatal or non-fatal CHD ( n = 1035 ) , and who were matched by age , gender , and enrollment time to 1920 controls who remained free of CHD . Electrophoretic characteristics of LDL particles were measured using 2 - 16 % polyacrylamide gradient gel electrophoresis . Concentrations of LDL-C(<255 A ) were higher in cases than controls in men ( 1.34 + /- 0.88 vs. 1.15 + /- 0.80 mmol/L , P < 0.001 ) as well as in women ( 1.12 + /- 0.84 vs. 0.94 + /- 0.74 mmol/L , P < 0.001 ) . The unadjusted odds ratio ( OR ) for future CHD in men of the top tertile of LDL-C(<255 A ) was 1.68 ( 95 % CI , 1.33 - 2.13 ; P < 0.001 ) whereas in women the unadjusted OR was 1.53 ( 95 % CI , 1.13 - 2.07 ; P < 0.001 ) . However , after further adjustments for confounding variables , the association between LDL-C(<255 A ) and CHD was no longer significant in men and in women . CONCLUSION Cholesterol concentrations in different LDL subclasses show different relationships with CHD risk in this European cohort Background — Changes in conventional lipid risk factors with gemfibrozil treatment only partially explain the reductions in coronary heart disease ( CHD ) events experienced by men in the Veterans Affairs High-Density Lipoprotein Intervention Trial ( VA-HIT ) . We examined whether measurement of low-density lipoprotein ( LDL ) and high-density lipoprotein ( HDL ) particle subclasses provides additional information relative to CHD risk reduction . Methods and Results — This is a prospect i ve nested case-control study of 364 men with a new CHD event ( nonfatal myocardial infa rct ion or cardiac death ) during a 5.1-year ( median ) follow-up and 697 age-matched controls . Nuclear magnetic resonance ( NMR ) spectroscopy was used to quantify levels of LDL and HDL particle subclasses and mean particle sizes in plasma obtained at baseline and after 7 months of treatment with gemfibrozil or placebo . Odds ratios for a 1-SD increment of each lipoprotein variable were calculated with adjusted logistic regression models . Gemfibrozil treatment increased LDL size and lowered numbers of LDL particles ( −5 % ) while raising numbers of HDL particles ( 10 % ) and small HDL subclass particles ( 21 % ) . Concentrations of these LDL and HDL particles achieved with gemfibrozil were significant , independent predictors of new CHD events . For total LDL and HDL particles , odds ratios predicting CHD benefit were 1.28 ( 95 % CI , 1.12 to 1.47 ) and 0.71 ( 95 % CI , 0.61 to 0.81 ) , respectively . Mean LDL and HDL particle sizes were not associated with CHD events . Conclusions — The effects of gemfibrozil on NMR-measured LDL and HDL particle subclasses , which are not reflected by conventional lipoprotein cholesterol measures , help to explain the demonstrated benefit of this therapy in patients with low HDL cholesterol Abstract Objective To examine the extent and nature of outcome reporting bias in a broad cohort of published r and omised trials . Design Retrospective review of publications and follow up survey of authors . Cohort All journal articles of r and omised trials indexed in PubMed whose primary publication appeared in December 2000 . Main outcome measures Prevalence of incompletely reported outcomes per trial ; reasons for not reporting outcomes ; association between completeness of reporting and statistical significance . Results 519 trials with 553 publications and 10 557 outcomes were identified . Survey responders ( response rate 69 % ) provided information on unreported outcomes but were often unreliable — for 32 % of those who denied the existence of such outcomes there was evidence to the contrary in their publications . On average , over 20 % of the outcomes measured in a parallel group trial were incompletely reported . Within a trial , such outcomes had a higher odds of being statistically non-significant compared with fully reported outcomes ( odds ratio 2.0 ( 95 % confidence interval 1.6 to 2.7 ) for efficacy outcomes ; 1.9 ( 1.1 to 3.5 ) for harm outcomes ) . The most commonly reported reasons for omitting efficacy outcomes included space constraints , lack of clinical importance , and lack of statistical significance . Conclusions Incomplete reporting of outcomes within published articles of r and omised trials is common and is associated with statistical non- significance . The medical literature therefore represents a selective and biased subset of study outcomes , and trial protocol s should be made publicly available OBJECTIVES To investigate the mechanisms by which bezafibrate retarded the progression of coronary lesions in the Bezafibrate Coronary Atherosclerosis Intervention Trial ( BECAIT ) , we examined the relationships of on-trial lipoproteins and lipoprotein subfractions to the angiographic outcome measurements . BACKGROUND BECAIT , the first double-blind , placebo-controlled , r and omized serial angiographic trial of a fibrate compound , showed that progression of focal coronary atherosclerosis in young survivors of myocardial infa rct ion could be retarded by bezafibrate treatment . METHODS A total of 92 dyslipoproteinemic men who had survived a first myocardial infa rct ion before the age of 45 years were r and omly assigned to treatment for 5 years with bezafibrate ( 200 mg three times daily ) or placebo ; 81 patients underwent baseline and at least one post-treatment coronary angiography . RESULTS In addition to the decrease in very low density lipoprotein ( VLDL ) cholesterol ( -53 % ) and triglyceride ( -46 % ) and plasma apolipoprotein ( apo ) B ( -9 % ) levels , bezafibrate treatment result ed in a significant increase in high density lipoprotein-3 ( HDL3 ) cholesterol ( + 9 % ) level and a shift in the low density lipoprotein ( LDL ) subclass distribution toward larger particle species ( peak particle diameter + 032 nm ) . The on-trial HDL3 cholesterol and plasma apo B concentrations were found to be independent predictors of the changes in mean minimum lumen diameter ( r=-0.23 , p < 0.05 ) , and percent ( % ) stenosis ( r = 0.30 , p < 0.01 ) , respectively . Decreases in small dense LDL and /or VLDL lipid concentrations were unrelated to disease progression . CONCLUSIONS Our results suggest that the effect of bezafibrate on progression of focal coronary atherosclerosis could be at least partly attributed to a rise in HDL3 cholesterol and a decrease in the total number of apo B-containing lipoproteins Background —The Diabetes Atherosclerosis Intervention Study showed that treatment with fenofibrate decreases progression of coronary atherosclerosis in subjects with type 2 diabetes . We determined whether on-treatment plasma lipid concentrations and LDL particle size contribute to the favorable effect of fenofibrate on the progression of coronary artery disease ( CAD ) . Methods and Results —A total of 418 subjects with type 2 diabetes were r and omly assigned to 200 mg micronized fenofibrate daily or placebo . The mean follow-up time was 39.6 months . LDL peak particle diameter ( LDL size ) was determined by polyacrylamide gradient gel electrophoresis from 405 subjects at baseline and at the end of the study . Progression of CAD was measured with quantitative coronary angiography . LDL size increased significantly more in the fenofibrate group than in the placebo group ( 0.98±1.04 versus 0.32±0.92 nm , P < 0.001 ) . In the combined group , small LDL size was significantly associated with progression of CAD measured as the increase of percentage diameter stenosis ( r = −0.16 , P = 0.002 ) and decreases in minimum ( r = −0.11 , P = 0.030 ) and mean ( r = −0.10 , P = 0.045 ) lumen diameter . High on-treatment LDL cholesterol , apolipoprotein B , and triglyceride concentrations were also associated with the progression of CAD . In regression analyses , small LDL size added to the effect of LDL cholesterol and apolipoprotein B on the progression of CAD . Similar associations were observed in the fenofibrate group , whereas in the placebo group , lipoprotein variables were not significantly correlated with the progression of CAD . Conclusions —Changes in LDL size and plasma lipid levels account for part of the antiatherogenic effect of fenofibrate in type 2 diabetes Accumulating evidence suggests that triglyceride-rich lipoproteins contribute to coronary artery disease . Using data from the Monitored Atherosclerosis Regression Study , an angiographic trial of middle-aged men and women r and omized to lovastatin or placebo , we investigated relationships between lipoprotein subclasses and progression of coronary artery atherosclerosis . Coronary artery lesion progression was determined by quantitative coronary angiography in low- grade ( < 50 % diameter stenosis ) , high- grade ( > or = 50 % diameter stenosis ) , and all coronary artery lesions in 220 baseline/2-year angiogram pairs . Analytical ultracentrifugation was used to measure lipoprotein masses that were statistically evaluated for treatment group differences and relationships to progression of coronary artery atherosclerosis . All low density lipoprotein ( LDL ) , intermediate density lipoprotein ( IDL ) , and very low density lipoprotein ( VLDL ) masses were significantly lowered and all high density lipoprotein ( HDL ) masses were significantly raised with lovastatin therapy . The mass of smallest LDL ( Svedberg flotation rate [ Sf ] 0 to 3 ) , IDL ( Sf 12 to 20 ) , all VLDL subclasses ( Sf 20 to 60 , Sf 60 to 100 , and Sf 100 to 400 ) , and peak LDL flotation rate were significantly related to the progression of coronary artery lesions , specifically low- grade lesions . Greater baseline levels of HDL3 , were related to a lower likelihood of coronary artery lesion progression . In multivariate analyses , small VLDL ( Sf 20 to 60 ) and HDL3 mass were the most important correlates of coronary artery lesion progression . These results provide further evidence for the importance of triglyceride-rich lipoproteins in the progression of coronary artery disease . In addition , these results present new evidence for the possible protective role of HDL3 in the progression of coronary artery lesions . More specific information on coronary artery lesion progression may be obtained through the study of specific apolipoprotein B-containing lipoproteins OB Output:	Commonly Used LDL Subfraction Tests and Terms If LDL subfractions are predictive of cardiovascular risk and are of incremental value when added to established cardiovascular risk factors , it remains to be determined whether the different characteristics of the LDL subfractions assessed by various methods would result in similar predictive abilities for estimating cardiovascular risk . Lipid research ers have proposed that small , dense LDL particles confer greater atherogenic risk than larger , less dense LDL particles ( 6 , 7 ) .
MS21815	*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 investigate the links between health warning labels ( WLs ) on cigarette packets and relapse among recently quit smokers . Design Prospect i ve longitudinal cohort survey . Setting Australia , Canada , the UK and the USA . Participants 1936 recent ex-smokers ( 44.4 % male ) from one of the first six waves ( 2002–2007 ) of the International Tobacco Control 4-Country policy evaluation survey , who were followed up in the next wave . Main outcome measures Whether participants had relapsed at follow-up ( approximately 1 year later ) . Results In multivariate analysis , very frequent noticing of WLs among ex-smokers was associated with greater relapse 1 year later ( OR : 1.52 , 95 % CI 1.11 to 2.09 , p<0.01 ) , but this effect disappeared after controlling for urges to smoke and self-efficacy ( OR : 1.29 , 95 % CI 0.92 to 1.80 , p=0.135 ) . In contrast , reporting that WLs make staying quit ‘ a lot ’ more likely ( compared with ‘ not at all ’ likely ) was associated with a lower likelihood of relapse 1 year later ( OR : 0.65 , 95 % CI 0.49 to 0.86 , p<0.01 ) and this effect remained robust across all models tested , increasing in some . Conclusions This study provides the first longitudinal evidence that health warnings can help ex-smokers stay quit . Once the authors control for greater exposure to cigarettes , which is underst and ably predictive of relapse , WL effects are positive . However , it may be that ex-smokers need to actively use the health consequences that WLs highlight to remind them of their reasons for quitting , rather than it being something that happens automatically . Ex-smokers should be encouraged to use pack warnings to counter urges to resume smoking . Novel warnings may be more likely to facilitate this BACKGROUND In June 2012 , Canada implemented new pictorial warnings on cigarette packages , along with package inserts with messages to promote response efficacy ( i.e. , perceived quitting benefits ) and self-efficacy ( i.e. , confidence to quit ) . This study assessed smokers ' attention toward warnings and inserts and its relationship with efficacy beliefs , risk perceptions and cessation at follow-up . METHODS Data were analyzed in 2015 from a prospect i ve online consumer panel of adult Canadian smokers surveyed every four months between September 2012 and September 2014 . Generalized Estimating Equation models were estimated to assess associations between reading inserts , reading warnings and efficacy beliefs ( self-efficacy , response efficacy ) , risk perceptions , quit attempts of any length , and sustained quit attempts ( i.e. , 30days or more ) at follow-up . Models adjusted for socio-demographics , smoking-related variables , and time-in- sample effects . RESULTS Over the study period , reading warnings significantly decreased ( p<0.0001 ) while reading inserts increased ( p=0.004 ) . More frequent reading of warnings was associated independently with stronger response efficacy ( Boften/very often vs never=0.28 , 95 % CI : 0.11 - 0.46 ) and risk perceptions at follow-up ( Boften/very often vs never=0.31 , 95 % CI : 0.06 - 0.56 ) . More frequent reading of inserts was associated independently with stronger self-efficacy to quit at follow-up ( Btwice or more vs none=0.30 , 95 % CI : 0.14 - 0.47 ) , quit attempts ( ORtwice or more vs none=1.68 , 95 % CI : 1.28 - 2.19 ) , and sustained quit attempts ( ORtwice or more vs none=1.48 , 95 % CI : 1.01 - 2.17 ) . CONCLUSIONS More frequent reading of inserts was associated with self-efficacy to quit , quit attempts , and sustained quitting at follow-up , suggesting that inserts complement pictorial HWLs Objectives : To examine the impact of health warnings on smokers by comparing the short-term impact of new graphic ( 2006 ) Australian warnings with : ( i ) earlier ( 2003 ) United Kingdom larger text-based warnings ; ( ii ) and Canadian graphic warnings ( late 2000 ) ; and also to extend our underst and ing of warning wear-out . Methods : The International Tobacco Control Policy Evaluation Survey ( ITC Project ) follows prospect i ve cohorts ( with replenishment ) of adult smokers annually ( five waves : 2002–2006 ) , in Canada , United States , UK and Australia ( around 2000 per country per wave ; total n = 17 773 ) . Measures were of pack warning salience ( reading and noticing ) ; cognitive responses ( thoughts of harm and quitting ) ; and two behavioural responses : forgoing cigarettes and avoiding the warnings . Results : All four indicators of impact increased markedly among Australian smokers following the introduction of graphic warnings . Controlling for date of introduction , they stimulated more cognitive responses than the UK ( text-only ) changes , and were avoided more , did not significantly increase forgoing cigarettes , but were read and noticed less . The findings also extend previous work showing partial wear-out of both graphic and text-only warnings , but the Canadian warnings have more sustained effects than UK ones . Conclusions : Australia ’s new health warnings increased reactions that are prospect ively predictive of cessation activity . Warning size increases warning effectiveness and graphic warnings may be superior to text-based warnings . While there is partial wear-out in the initial impact associated with all warnings , stronger warnings tend to sustain their effects for longer . These findings support arguments for governments to exceed minimum FCTC requirements on warnings Recent research has made significant progress identifying measures of the perceived effectiveness ( PE ) of persuasive messages and providing evidence of a causal link from PE to actual effectiveness ( AE ) . This article provides additional evidence of the utility of PE through unique analysis and consideration of another dimension of PE important to underst and ing the PE – AE association . Current smokers ( N=1,139 ) watched four r and omly selected antismoking Public Service Announcements ( PSAs ) . PE scores aggregated by message were used instead of individual PE scores to create a summed total , minimizing the likelihood that PE perceptions are consequences of an individual 's intention to quit , supporting instead the PE → AE order . Linear regression analyses provide evidence of PE 's positive and significant influence on smoking-cessation-related behavioral intentions The objective of this research was to compare the response of adult smokers in Malaysia to newly proposed pictorial cigarette warnings against the current text-only warnings . The study population included 140 adult male smokers who were enrolled in a r and omized trial to view either the new pictorial warnings ( intervention ) or the old text-only warnings ( control ) . Participants completed pre-exposure and post-exposure question naires that assessed their awareness of the health risks of smoking , response to the package warnings , and interest in quitting smoking . Exposure to the pictorial warnings result ed in increased awareness of the risks of smoking , stronger behavioral response to the warnings and increased interest in quitting smoking . The new warnings in Malaysia will increase smokers ’ knowledge of the adverse health effects of smoking and have a positive effect on interest in quitting Background Cigarette smoking is considered the first preventable cause of death in the world . Social , familial , and personal factors play an important role in prevention or cessation of smoking . Educating the public in order to enhance their knowledge , change their attitude and improve their habits is also effective in this respect . In 2007 , the executive protocol of the Comprehensive Law on Smoking Control was compiled in the Ministry of Health and according to the Article 5 of this law pictorial health warning labels had to be applied on cigarette packaging . This study was design ed and conducted in 2 phases of before and 9 months after the implementation of this law and evaluated the effect of it on smokers ’ knowledge , attitude and pattern of smoking . Material s and Methods This was a cross-sectional descriptive study conducted to evaluate the effect of cigarette packs ’ pictorial health warning labels on the knowledge , attitude and smoking pattern of smokers residing in Tehran . After calculating the size of under study population and estimation of the exclusions , 1731 subjects were r and omly selected using the multiphase cluster method from the 22 districts of Tehran . Data were collected using a question naire design ed according to the st and ard question naire of the World Health Organization ( WHO ) and International Union Against Tuberculosis and Lung Disease ( IUATLD ) . Qualitative and quantitative value and reliability of the variables including cigarette consumption , knowledge about the law , and pattern of smoking were evaluated in 2 phases and the quality of pictures and their effects on the mentioned variables were assessed in the 2nd phase . Results Before adopting the pictorial warning labels in the first phase of the study , 1731 respondents were evaluated out of which 71.8 % were males and 28.2 % were females . These cases had an average of 17.6±12.3 years history of smoking . A total of 38 % ( 675 subjects ) used Iranian cigarette br and s and 39.5 % were aware of the implementation of pictorial health warning labels on cigarette packs . In terms of smokers ’ attitude towards the implementation of this law , they mostly had no opinion about it . A total of 33.3 % stated that they may cut down on smoking as the result of this law . Men had a higher percentage of smoking a cigarette first thing in the morning before breakfast and women had a higher rate of consuming foreign cigarette br and s ( P < 0.001 ) . In the second phase of the study , 1590 cases of the phase 1 subjects participated . Subjects had a significantly higher knowledge about the implementation of pictorial health warning labels on cigarette packs ( P < 0.001 ) . Attitude towards this law did not change significantly compared to the first phase although the mean score improved by 0.07 % . Enforcement of this law result ed in decreased consumption in 7.6 % of the participants . However , the Wilcoxon test did not show any significant difference . In terms of the quality of pictures , 61.6 % had no opinion , and 28.7 % expressed that the pictures had poor quality . No significant difference was observed between the Iranian or foreign br and s in terms of smoking rate after applying the pictorial warning labels . Conclusion We believed that the smoking rate would decrease after applying the pictorial health warning labels on cigarette packs . However , it did not happen . Also , adopting these labels did not have a significant effect on smokers changing their favorite br and from Iranian to foreign br and s or vice versa . Type and quality of pictures require major revision and corrections This study reports consumer reactions to the graphic health warnings selected by the Food and Drug Administration to be placed on cigarette packs in the United States . We recruited three sets of respondents for an experimental study from a national opt-in e-mail list sample : ( i ) current smokers aged 25 or older , ( ii ) young adult smokers aged 18 - 24 and ( iii ) youth aged 13 - 17 who are current smokers or who may be susceptible to initiation of smoking . Participants were r and omly assigned to be exposed to a pack of cigarettes with one of nine graphic health warnings or with a text-only warning statement . All three age groups had overall strong negative emotional ( ß = 4.7 , P < 0.001 for adults ; ß = 4.6 , P < 0.001 for young adults and ß = 4.0 , P < 0.001 for youth ) and cognitive ( ß = 2.4 , P < 0.001 for adults ; ß = 3.0 , P < 0.001 for young adults and ß = 4.6 , P < 0.001 for youth ) reactions to the proposed labels . The strong negative emotional and cognitive reactions following a single exposure to the graphic health warnings suggest that , with repeated exposures over time , graphic health warnings may influence smokers ' beliefs , intentions and behaviors Background It is important to monitor whether anti-smoking messages ( if any ) are noticed by the public in China and whether they have any impact on smokers ’ quitting behaviours over time Purpose This study aim ed to examine Chinese smokers ' exposure to anti-smoking messages in a range of channels and to determine if exposure was associated with subsequent quit attempts . Method A prospect i ve cohort design was employed . Participants were 6,509 adult smokers who completed at least one of the first three waves ( 2006–2009 ) of the International Tobacco Control ( ITC ) China Survey sample d from six Chinese cities . The main measures were reported exposure to anti-smoking messages in a range of channels and smokers ' subsequent quit attempts . Generalized Estimating Equations ( GEE ) modelling was used to combine respondents from all three waves while accounting for inherent within-person correlation . Results The overall exposure levels to anti-smoking messages were low and varied between cities and from one channel to another . Television was the medium with the greatest overall exposure ( over 50 % in almost all the cities across all the waves ) . After controlling for a range of covariates , higher level of combined exposure were positively related to higher subsequent quit attempts ( adjusted odds ratio = 1.03 , 95 % CI 1.02 ~ 1.05 , p < .001 ) ; among the individual channels , exposures in newspapers and on posters were significant in their own right . Conclusion The findings suggest that anti-smoking warning messages have the potential to stimulate Chinese smokers to make quit attempts , but they also indicate that the levels and strength of warning messages in China need to be increased . China should consider adopting proven international practice s , including m and ating pictorial health warnings on cigarette packages , adopting prominent point-of-sale warnings , and carrying out strong and ongoing mass media campaigns INTRODUCTION Article 11 of the World Health Organ Output:	Strengthened warnings increased attention to warnings , recall of warnings , and thinking about the health risks of smoking . Strengthened warnings also increased several perceived effectiveness outcomes , including perceptions that warnings reduce smoking and motivate quitting . Strengthened cigarette pack warnings achieve their goal of attracting attention and enhancing motivation to act .
MS21816	*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 Dormant pulmonary vein ( PV ) conduction can be provoked by adenosine triphosphate ( ATP ) after extensive encircling pulmonary vein isolation ( EEPVI ) . However , the clinical implication of reconnection between the left atrium ( LA ) and isolated PVs provoked by ATP ( ATP-reconnection ) remains unknown . METHODS AND RESULTS We studied the clinical consequences of ATP-reconnection during intravenous isoproterenol infusion ( ISP-infusion ) . EEPVI severs conduction between the LA and ipsilateral PVs at their junction . Radiofrequency energy is applied at a distance from the PV ostia guided by double Lasso catheters placed within the ipsilateral superior and inferior PVs . This study comprised 82 patients ( 67 men , 56 + /- 9 years old ) with atrial fibrillation ( AF ) who underwent injection of ATP during ISP infusion after successful EEPVI ( ATP(+ ) group ) . We compared clinical characteristics of 170 patients who underwent earlier EEPVI prior to our use of ATP injection after successful EEPVI ( ATP(N/D ) group ) with those of ATP(+ ) group patients who underwent one session of EEPVI . ATP-reconnection occurred in 34 ( 41 % ) of 82 ATP(+ ) group patients . Additional radiofrequency applications were performed to eliminate ATP-reconnection in all ipsilateral PVs . Continuous ATP-reconnection of more than 20 seconds duration occurred in six ( 7.3 % ) of 82 patients . A total of 102 ( 60 % ) of 170 patients in the ATP(N/D ) group had no recurrence of AF , whereas 60 ( 73 % ) of 82 ATP(+ ) group patients who underwent only one EEPVI session have had no recurrence of AF in a 6.1 + /- 3.3-month follow-up period ( P = 0.04 ) . CONCLUSION Radiofrequency application for provoked ATP-reconnection may reduce clinical AF recurrence BACKGROUND Catheter ablation ( CA ) by wide encirclement of pulmonary veins ( WEPV ) restores sinus rhythm in up to 95 % . Complex PV-left atrial ( LA ) connections make achieving electrical isolation ( EI ) challenging . We examined anatomical and technical features associated with resistance to EI during WEPV in a prospect i ve study . METHODS One hundred one consecutive patients with symptomatic AF underwent first-time CA guided by electroanatomic mapping and CT integration ( Cartomerg ) . Following double-transseptal access , WEPV was performed . After completion of PV encirclement , the line was mapped and where no signal could be obtained , CA was performed inside the WE line at the site of earliest PV breakthrough on the circular mapping catheter . Sites of EI were tagged . Anatomic studies of corresponding regions of the venoatrial junction in 24 adult hearts were performed . RESULTS Sites resistant to EI were located at the inferior quadrant ( P < 0.001 ) for the RSPV , superior quadrant ( P < 0.001 ) for the RIPV , and the inferior and anterior quadrants ( P < 0.001 ) for the LSPV . EI was significantly less frequent at the posterior quadrant ( P < 0.001 ) for the LIPV . To achieve EI , CA was necessary inside the WE on the intervenous ridge on the right in 51 % and on the left in 41 % . The LPV/LAA ridge was investigated by anatomic studies that demonstrated considerable variation in the narrowest width ( 3 - 23.7 mm ) and transmural thickness ( 1 - 5 mm ) . CONCLUSION Sites of EI after WEPV have a preferential distribution determined by anatomic features . CA on the intervenous ridge is required in a significant proportion of patients to achieve EI . Atrial folds and ridges increase myocardial thickness creating technical and anatomic challenges for achieving transmural lesions AIMS Pulmonary vein ( PV ) isolation is a curative treatment for patients with atrial fibrillation . The aim of this study was to evaluate prospect ively the effects of adenosine administration on the PV activity and atrio-venous conduction after PV isolation . METHODS AND RESULTS Twenty-nine patients ( 21 m ; age : 55+/-8 years ) were su bmi tted to ostial PV isolation guided by basket catheter recordings . After successful isolation , the effects of a 12 mg intravenous bolus of adenosine were tested in 62 PVs . In 22/62 PVs ( 35 % ) , left atrium (LA)-to-PV conduction was transiently ( 16.6+/-7.1 s , range : 3.8 - 27.9 s ) or permanently ( 3 PVs ) restored in response to adenosine administration . The prevalence of this phenomenon was 39 % in left superior PVs , 43 % in right superior PVs , and 22 % in left inferior PVs ( p=0.365 ) . It occurred more frequently in the presence of dissociated PV activity ( 11/15 PVs , 73 % vs. 11/47 PVs , 23 % ; p=0.002 ) , whereas it was not influenced by the median duration of the radiofrequency current ( RFC ) delivery for each PV [ 19 ( IQR : 12 - 26 ) min vs. 16 ( IQR : 11 - 24 ) min : p=0.636 ] . A lengthening or shortening of the LA-PV conduction time was observed at LA-PV conduction appearance and disappearance in 36 % and 55 % of the cases , respectively . Further RFC applications ( median : 5.5 min , IQR : 4 - 11 min ) at the residual conduction breakthrough(s ) indicated by the basket catheter recordings definitively eliminated adenosine-induced recovery of LA-PV conduction in all cases . Finally , when present , intrinsic PV discharge was invariably depressed by adenosine administration . CONCLUSIONS Adenosine may transiently or permanently re-establish LA-PV conduction after apparently successful PV isolation . This phenomenon is abolished by additional RFC delivery . However , its possible influence on the clinical results of PV ablation must be evaluated by properly design ed , r and omized studies INTRODUCTION Catheter ablation for paroxysmal AF ( PAF ) is limited by an unacceptable recurrence rate , mainly due to pulmonary vein ( PV ) reconnection . Strategies to minimize reconnection include adenosine infusion and also a waiting period of 30 minutes after PV isolation . The aim of the present study was to assess whether these two strategies revealed the same conduction gap . METHODS AND RESULTS In total , 88 consecutive patients ( 54 males , mean age of 60 years ) with drug refractory PAF underwent circumferential PV isolation ( CPVI ) . After isolation of ipsilateral PVs , with entry and exit block checked using a circular mapping catheter , 20 mg ATP was injected during isoproterenol infusion to reveal dormant conduction gap(s ) . Unless the reconnection revealed by ATP persisted , PVs were further remapped with the circular mapping catheter at 30 minutes postisolation . Totally , PV reconnection was observed in 56 ( 64 % ) patients . 24.3 % veins ( 80/329 ) were found reconnected . Re assessment at 30 minutes postablation was more efficient as compared to ATP induction ( 19.8 % vs 14.6 % for ATP ) . The agreement between these 2 methods is moderate ( kappa value = 0.50 ) . In veins that transiently reconnected after ATP administration and later observed at 30 minutes postablation , 94 % ( 17 of 19 ) of them were found being reconnected with the same gap . CONCLUSION Acute PV reconnection is common , occurring in 64 % of patients , as detected by adenosine infusion and waiting time . Each shows a unique quality as compared to one another . The combined use of these 2 methods may reduce the AF recurrence rate after CPVI BACKGROUND Pulmonary vein ( PV ) isolation ( PVI ) has emerged as an effective therapy for paroxysmal atrial fibrillation ( AF ) . However , AF recurs in up to 50 % of patients , generally because of recovery of PV conduction . Adenosine given during the initial procedure may reveal dormant PV conduction , thereby identifying the need for additional ablation , leading to improved outcomes . The Adenosine Following Pulmonary Vein Isolation to Target Dormant Conduction Elimination ( ADVICE ) study is a prospect i ve multicentre r and omized trial assessing the impact of adenosine-guided PVI in preventing AF recurrences . METHODS Patients undergoing a first PVI procedure for paroxysmal AF will be recruited . After st and ard PVI is completed , all patients will receive intravenous adenosine in an attempt to unmask dormant conduction . If dormant conduction is elicited , patients will be r and omized to no further ablation ( control group ) or additional adenosine-guided ablation until dormant conduction is abolished . If no dormant conduction is revealed , r and omly selected patients will be followed in a registry . The primary outcome is time to first documented symptomatic AF recurrence . Assuming that dormant conduction is present in 50 % of patients post PVI and symptomatic AF recurs in 45 % of controls , 244 patients with dormant conduction will be required to obtain > 90 % power to detect a difference of 20 % . Thus , a total of 488 patients will be enrolled and followed for 12 months . CONCLUSION The ADVICE trial will assess whether a PVI strategy incorporating elimination of dormant conduction unmasked by intravenous adenosine will decrease the rate of recurrent symptomatic AF compared with st and ard PVI BACKGROUND Although it is well recognized that recovery of pulmonary vein ( PV ) conduction is common among patients who fail atrial fibrillation ( AF ) ablation , little is known about the precise time course of recurrence . OBJECTIVE To determine the incidence and time course of early recurrence of conduction after PV isolation during AF ablation . METHODS The patient population was composed of 14 consecutive patients ( 9 men [ 64 % ] ; age 56 + /- 7 years ) with AF who underwent radiofrequency catheter ablation via circumferential ablation with PV isolation , determined by a circular mapping catheter . After successful isolation of the PVs , repeat circular electrode recordings from each PV were obtained at 30 and 60 minutes . RESULTS After complete isolation of all PVs , early PV recurrence was observed in 13 ( 93 % ) patients and 26 veins ( 50 % ) . Seventeen veins ( 33 % ) showed a first recurrence at 30 minutes , while nine veins ( 17 % ) showed a first recurrence at 60 minutes . CONCLUSION The results reveal an extremely high rate of early recurrence of PV conduction following AF ablation . It is particularly notable that about one-fifth of the veins remained isolated at 30 minutes , but subsequently developed recurrence between 30 and 60 minutes . Of the veins that showed early recurrence , one-third developed a first recurrence at 60 minutes . These findings suggest that AF ablation procedures should incorporate a 60-minute waiting period after initial isolation in order to detect early recurrence of conduction Output:	Routine adenosine testing is associated with an improvement in freedom from AF post-PVI . Paradoxically acute adenosine-induced PV reconnection may portend a greater likelihood of AF recurrence despite additional ablation .
MS21817	*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 Although acute renal failure ( ARF ) is believed to be common in the setting of critical illness and is associated with a high risk of death , little is known about its epidemiology and outcome or how these vary in different regions of the world . OBJECTIVES To determine the period prevalence of ARF in intensive care unit ( ICU ) patients in multiple countries ; to characterize differences in etiology , illness severity , and clinical practice ; and to determine the impact of these differences on patient outcomes . DESIGN , SETTING , AND PATIENTS Prospect i ve observational study of ICU patients who either were treated with renal replacement therapy ( RRT ) or fulfilled at least 1 of the predefined criteria for ARF from September 2000 to December 2001 at 54 hospitals in 23 countries . MAIN OUTCOME MEASURES Occurrence of ARF , factors contributing to etiology , illness severity , treatment , need for renal support after hospital discharge , and hospital mortality . RESULTS Of 29 269 critically ill patients admitted during the study period , 1738 ( 5.7 % ; 95 % confidence interval [ CI ] , 5.5%-6.0 % ) had ARF during their ICU stay , including 1260 who were treated with RRT . The most common contributing factor to ARF was septic shock ( 47.5 % ; 95 % CI , 45.2%-49.5 % ) . Approximately 30 % of patients had preadmission renal dysfunction . Overall hospital mortality was 60.3 % ( 95 % CI , 58.0%-62.6 % ) . Dialysis dependence at hospital discharge was 13.8 % ( 95 % CI , 11.2%-16.3 % ) for survivors . Independent risk factors for hospital mortality included use of vasopressors ( odds ratio [ OR ] , 1.95 ; 95 % CI , 1.50 - 2.55 ; P<.001 ) , mechanical ventilation ( OR , 2.11 ; 95 % CI , 1.58 - 2.82 ; P<.001 ) , septic shock ( OR , 1.36 ; 95 % CI , 1.03 - 1.79 ; P = .03 ) , cardiogenic shock ( OR , 1.41 ; 95 % CI , 1.05 - 1.90 ; P = .02 ) , and hepatorenal syndrome ( OR , 1.87 ; 95 % CI , 1.07 - 3.28 ; P = .03 ) . CONCLUSION In this multinational study , the period prevalence of ARF requiring RRT in the ICU was between 5 % and 6 % and was associated with a high hospital mortality rate Background Correct antibiotic dosing remains a challenge for the clinician . The aim of this study was to assess the influence of augmented renal clearance on pharmacokinetic/pharmacodynamic target attainment in critically ill patients receiving meropenem or piperacillin/tazobactam , administered as an extended infusion . Methods This was a prospect i ve , observational , pharmacokinetic study executed at the medical and surgical intensive care unit at a large academic medical center . Elegible patients were adult patients without renal dysfunction receiving meropenem or piperacillin/tazobactam as an extended infusion . Serial blood sample s were collected to describe the antibiotic pharmacokinetics . Urine sample s were taken from a 24-hour collection to measure creatinine clearance . Relevant data were drawn from the electronic patient file and the intensive care information system . Results We obtained data from 61 patients and observed extensive pharmacokinetic variability . Forty-eight percent of the patients did not achieve the desired pharmacokinetic/pharmacodynamic target ( 100 % f T > MIC ) , of which almost 80 % had a measured creatinine clearance > 130 mL/min . Multivariate logistic regression demonstrated that high creatinine clearance was an independent predictor of not achieving the pharmacokinetic/pharmacodynamic target . Seven out of nineteen patients ( 37 % ) displaying a creatinine clearance > 130 mL/min did not achieve the minimum pharmacokinetic/pharmacodynamic target of 50 % f T > MIC . Conclusions In this large patient cohort , we observed significant variability in pharmacokinetic/pharmacodynamic target attainment in critically ill patients . A large proportion of the patients without renal dysfunction , most of whom displayed a creatinine clearance > 130 mL/min , did not achieve the desired pharmacokinetic/pharmacodynamic target , even with the use of alternative administration methods . Consequently , these patients may be at risk for treatment failure without dose up-titration BACKGROUND Higher daptomycin doses are advocated for select methicillin-resistant Staphylococcus aureus (MRSA)-related infections , but the probabilities of target attainment ( PTA ) and toxicity of these doses have not been characterized in critically ill patients . METHODS We evaluated the plasma pharmacokinetics ( PK ) and clinical outcomes of a cohort of critically ill patients treated with daptomycin 6 - 8 mg/kg/day for primarily Staphylococcus species-related infections . Daptomycin concentrations were measured intensively over the initial 96-hour dosing period . Data were modeled by population PK analyses , and Monte Carlo simulation was used to estimate the probabilities of effect and toxicity with st and ard and alternate dosing regimens . RESULTS Fifty patients with a mean ( SD ) age of 69.7 ( 12.2 ) years , weight 74.5 ( 20.3 ) kg , and creatinine clearance 56.8 ( 38.2 ) mL/minute were enrolled with measurements of 12 ( 2.2 ) daptomycin sample s per patient . Significantly lower daptomycin exposures were observed despite comparable doses in a subset of patients ( n = 13 ) with augmented clearance ( CL ) . No covariates of CL were identified , but this subset was significantly more likely to be in severe sepsis or septic shock , have higher Sequential Organ Failure Assessment scores , and MRSA bacteremia . In-hospital mortality was significantly higher ( 30.7 % vs 10.8 % ) in patients with augmented daptomycin CL . Use of an empiric fixed dose of 750 mg of daptomycin is predicted to achieve a comparable PTA with a lower probability of toxicity as compared to the use of 10 mg/kg in critically ill patients . CONCLUSIONS A re appraisal of current daptomycin dosing recommendations is needed to improve the PTA and reduce toxicity among critically ill patients Background In ICU patients with normal serum creatinine ( SCr ) , a state of increased renal drug excretion has been described ( creatinine clearance ≥130 ml/min/1.73 m2 ) , and named augmented renal clearance ( ARC ) . In ICU patients , the accuracy of GFR estimates is insufficient . However , in clinical practice , the physician has not at one ’s disposal patient measured creatinine clearance ( CrCl ) when prescribing . The primary objective of this study was to assess the accuracy of 4 formulas to estimate GFR ( Cockcroft-Gault ( CG ) , Robert , sMDRD , and CKD-EPI formulas ) with other covariates to detect ARC in ICU patients . Methods We enroled 360 consecutive ICU patients with normal SCr in this prospect i ve observational study conducted in a primary teaching hospital . Comparisons between CrCl values and 4 estimated GFR ( eGFR ) formulas were estimated . Results In these 360 patients , ARC was observed in 33 % of patients most of them trauma . Individual predictive values of equations were poor and the phenomenon increased in ARC subgroup . CG and CKD-EPI were more accurate to detect an ARC . Multivariable analysis showed that the best-fitting model included 3 factors independently correlated to ARC : trauma patients , cut-off values of age ≤58 years , and CKD-EPI more than 108 ml/min/1.73 m2 . Conclusions In ICU patients with normal SCr , eGFR formulas are imprecise in assessing CrCl . If measured CrCl must be ideally used to detect modifications of the renal function , in clinical practice , age , reason for admission , and CKD-EPI could be used as screening tool to identify ARC Our objective was to prospect ively determine the factors influencing the probability of a good microbiological or clinical outcome in patients with nosocomial pneumonia treated with a fluoroquinolone . Levofloxacin was administered as an infusion of 500 mg/h for 1.5 h ( total dose , 750 mg ) . For patients with Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus , a second drug was added ( ceftazidime or piperacillin/tazobactam for P. aeruginosa and vancomycin for methicillin-resistant S. aureus ) . Population pharmacokinetic studies of 58 patients demonstrated that this population h and led the drug differently from population s of volunteers . Multivariate logistic regression analysis ( n=47 patients ) demonstrated that only the age of the patient and the achievement of an area under the curve : minimum inhibitory concentration ratio of > or = 87 had a significant effect on eradication of the pathogen ( P<.001 ) . Achieving the breakpoint made the patient 4 times more likely to achieve eradication . The effect was greatest in patients > or = 67 years old Introduction The aim of this study was to explore changes in glomerular filtration ( GFR ) and renal tubular function in critically ill patients at risk of augmented renal clearance ( ARC ) , using exogenous marker compounds . Methods This prospect i ve , observational pharmacokinetic ( PK ) study was performed in a university-affiliated , tertiary-level , adult intensive care unit ( ICU ) . Patients aged less than or equal to 60 years , manifesting a systemic inflammatory response , with an expected ICU length of stay more than 24 hours , no evidence of acute renal impairment ( plasma creatinine concentration < 120 μmol/L ) and no history of chronic kidney disease or renal replacement therapy were eligible for inclusion . The following study markers were administered concurrently : sinistrin 2,500 mg ( Inutest ; Laevosan , Linz , Austria ) , p-aminohippuric acid ( PAH ) 440 mg ( 4 % p-aminohippuric acid sodium salt ; CFM Oskar Tropitzsch , Marktredwitz , Germany ) , rac-pindolol 5 or 15 mg ( Barbloc ; Alphapharm , Millers Point , NSW , Australia ) and fluconazole 100 mg ( Diflucan ; Pfizer Australia Pty Ltd , West Ryde , NSW , Australia ) . Plasma concentrations were then measured at 5 , 10 , 15 , 30 , 60 and 120 minutes and 4 , 6 , 12 and 24 hours post-administration . Non-compartmental PK analysis was used to quantify GFR , tubular secretion and tubular reabsorption . Results Twenty patients were included in the study . Marker administration was well tolerated , with no adverse events reported . Sinistrin clearance as a marker of GFR was significantly elevated ( mean , 180 ( 95 % confidence interval ( CI ) , 141 to 219 ) ml/min ) and correlated well with creatinine clearance ( r = 0.70 , P < 0.01 ) . Net tubular secretion of PAH , a marker of tubular anion secretion , was also elevated ( mean , 428 ( 95 % CI , 306 to 550 ) ml/min ) , as was net tubular reabsorption of fluconazole ( mean , 135 ( 95 % CI , 100 to 169 ) ml/min ) . Net tubular secretion of (S)- and (R)-pinodolol , a marker of tubular cation secretion , was impaired . Conclusions In critically ill patients at risk of ARC , significant alterations in glomerular filtration , renal tubular secretion and tubular reabsorption are apparent . This has implication s for accurate dosing of renally eliminated drugs 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 Output:	An influence of ARC on antimicrobial pharmacokinetics has been observed , with ARC consistently being associated with subtherapeutic antibiotic plasma concentrations . Conclusion ARC is a prevalent condition in critically ill patients , especially in young people , with urinary CrCl being the best diagnostic method because mathematical estimates tend to underestimate CrCl . ARC increases renal drug elimination and has a clear influence on certain antimicrobial plasma levels , but is yet to define its impact on clinical outcomes and on pharmacokinetics of other types of drugs .
MS21818	*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 number of studies with conflicting results have evaluated the effect of chewing gum on post-operative gastrointestinal recovery in patients after major colorectal surgery . Objective The objective of the study was to study the efficacy of chewing gum in patients with rectal cancer after elective open proctectomy only . Methods A r and omized controlled clinical trial was performed . We recruited patients who would undergo elective open proctectomy for rectal cancer in Sichuan Academy of Medical Sciences and Sichuan Provincial People 's Hospital . Patients in the intervention arm received chewing gum 3 times a day postoperatively . All patients in the trial were placed on the same perioperative management and st and ardized post-operative care plans . The primary outcome was time to the first peristalsis sounds , time to first flatus and the first defecation . Results A total of 89 patients were recruited . The time to the first flatus was 42.33 ± 3.46 h in the gum group and 49.20 ± 1.42 h in the control group ( p < 0.05 ) . The time to the first defecation was significantly shorter in the gum-chewing group than in the control group ( 66.07 ± 2.36 vs. 78.37 ± 1.62 h ; p < 0.05 ) . Post-operative ileus ( POI ) was confirmed in 2 patients in the gum-chewing group and in 7 in the control group ( 7.0 % vs. 23.9 % ; p = 0.028 ) . Discussion The present study suggests that chewing gum is a method to reduce the time to first flatus , time to first defecation and POI in patients undergoing elective open proctectomy for rectal cancer BACKGROUND : Prolonged intestinal paralysis can be a problem after gastrointestinal surgery . Several systematic review s and meta-analyses have suggested the efficacy of gum chewing for the prevention of postoperative ileus . OBJECTIVE : The purpose of this study was to examine the efficacy of gum chewing for the recovery of bowel function after surgery for left-sided colorectal cancer and to determine the physiological mechanism underlying the effect of gum chewing on bowel function . DESIGN : This was a single-center , placebo-controlled , parallel-group , prospect i ve r and omized trial . SETTING S : The study was conducted at a general hospital in Japan . PATIENTS : Forty-eight patients with left-sided colorectal cancer were included . INTERVENTIONS : The patients were r and omly assigned to a gum group ( N = 25 ) and a control group ( N = 23 ) . Four patients in the gum group and 1 in the control group were subsequently excluded because of difficulties in continuing the trial , result ing in the analysis of 21 and 22 patients in the respective groups . Patients in the gum group chewed commercial gum 3 times a day for ≥5 minutes each time from postoperative day 1 to the first day of food intake . MAIN OUTCOME MEASURES : The time to first flatus and first bowel movement after the operation were recorded , and the colonic transit time was measured . Gut hormones ( gastrin , des-acyl ghrelin , motilin , and serotonin ) were measured preoperatively , perioperatively , and on postoperative days 1 , 3 , 5 , 7 , and 10 . RESULTS : Gum chewing did not significantly shorten the time to the first flatus ( 53 ± 2 vs 49 ± 26 hours ; p = 0.481 ; gum vs control group ) , time to first bowel movement ( 94 ± 44 vs 109 ± 34 hours ; p = 0.234 ) , or the colonic transit time ( 88 ± 28 vs 88 ± 21 hours ; p = 0.968 ) . However , gum chewing significantly increased the serum levels of des-acyl ghrelin and gastrin . LIMITATIONS : The main limitation was a greater rate of complications than anticipated , which limited the significance of the findings . CONCLUSIONS : Gum chewing changed the serum levels of des-acyl ghrelin and gastrin , but we were unable to demonstrate an effect on the recovery of bowel function HYPOTHESIS Gum chewing after elective open colon resection may stimulate bowel motility and decrease duration of postoperative ileus . DESIGN AND SETTING Prospect i ve , r and omized study in a community-based teaching hospital . PATIENTS Thirty-four patients undergoing elective open sigmoid resections for recurrent diverticulitis or cancer . MAIN OUTCOME MEASURES First feelings of hunger , time to first flatus , time to first bowel movement , length of hospital stay , and complications . RESULTS A total of 34 patients were r and omized into 2 groups : a gum-chewing group ( n = 17 ) or a control group ( n = 17 ) . The patients in the gum-chewing group chewed sugarless gum 3 times daily for 1 hour each time until discharge . Patient demographics , intraoperative , and postoperative care were equivalent between the 2 groups . All gum-chewing patients tolerated the gum . The first passage of flatus occurred on postoperative hour 65.4 in the gum-chewing group and on hour 80.2 in the control group ( P = .05 ) . The first bowel movement occurred on postoperative hour 63.2 in the gum-chewing group and on hour 89.4 in the control group ( P = .04 ) . The first feelings of hunger were felt on postoperative hour 63.5 in the gum-chewing group and on hour 72.8 in the control group ( P = .27 ) . There were no major complications in either group . The total length of hospital stay was shorter in the gum-chewing group ( day 4.3 ) than in the control group ( day 6.8 ) , ( P = .01 ) . CONCLUSIONS Gum chewing speeds recovery after elective open sigmoid resection by stimulating bowel motility . Gum chewing is an inexpensive and helpful adjunct to postoperative care after colectomy BACKGROUND Postoperative ileus generates a high impact on morbidity , hospital stay , and costs . OBJECTIVE To study the efficiency and safety of chewing gum to decrease postoperative ileus in colorectal surgery . METHOD A r and omized controlled trial was performed including 64 patients who underwent elective colorectal surgery with primary anastomosis in a tertiary referral center . Patients were divided in two groups : ( i ) A : gum chewing group ( n = 32 ) , and ( ii ) B : patients who had st and ard postoperative recovery ( n = 32 ) . RESULTS Postoperative ileus was observed in 6 % ( 2/32 ) of the gum-chewing group and in 21.8 % ( 7/32 ) in the st and ard postoperative recovery group , with an odds ratio of 0.167 ( 95 % CI : 0.37 - 0.75 ; p = 0.006 ) . Vomiting was present in two patients from group A and in eight from group B ( 6.25 vs. 25.0 % ; p = 0.03 ) . Passage of flatus within the first 48 hours was present in 30 patients from group A and in 20 from group B ( 94 vs. 63 % ; p = 0.002 ) . There was earlier oral feeding ( 96 ± 53 vs. 117 ± 65 hours ; p= 0.164 ) and a shorter length of hospital stay ( 7 ± 5 vs. 9 ± 5 days ; p= 0.26 ) in the gum-chewing group ( p N.S. ) . CONCLUSIONS The use of chewing gum after colorectal surgery was associated with less postoperative ileus and vomiting , and with an increased passage of flatus within the first 48 hours after surgery . Since gum chewing is an inexpensive procedure and is not associated with higher morbidity , it can be safely used for a faster postoperative recovery in elective colorectal surgery BACKGROUND Postoperative ileus limits early hospital discharge for patients who have undergone laparoscopic procedures . Sham feeding has been reported to enhance bowel motility . Here , the effect of gum chewing is evaluated as a convenient method to enhance postoperative recovery from ileus after laparoscopic colectomy . STUDY DESIGN A total of 19 patients who underwent elective laparoscopic colectomy for colorectal cancer participated in the study . Each patient was r and omly assigned to one of two groups : a gum-chewing group ( n = 10 , mean age 58.6 years , range 50 to 71 years ) or a control group ( n = 9 , mean age 60.6 years , range 45 to 80 years ) . The patients in the gum-chewing group chewed gum three times a day from the first postoperative AM until oral intake . The times of the first passage of flatus and defecation were recorded precisely . RESULTS The first passage of flatus was seen , on average , on postoperative day 2.1 in the gum-chewing group and on day 3.2 in the control group ( p < 0.01 ) . The first defecation was 2.7 days sooner in the gum-chewing group ( postoperative day 3.1 ) than in the control group ( 5.8 days ; p < 0.01 ) . All patients tolerated gum chewing on the first operative AM . The postoperative hospital stays for the gum-chewing and control groups were 13.5+/-3.0 days and 14.5+/-6.1 days , respectively . CONCLUSIONS Gum chewing aids early recovery from postoperative ileus and is an inexpensive and physiologic method for stimulating bowel motility . Gum chewing should be added as an adjunct treatment in postoperative care because it might contribute to shorter hospital stays Objective : Prolonged ileus — the failure of postoperative ileus to resolve within a few days after major abdominal surgery — leads to significant medical consequences for the patient and costs to the hospital system . The aim of this retrospective analysis of prospect ively collected data was to identify independent preoperative and intraoperative risk factors for prolonged ileus in a large consecutive series of patients who had undergone resection for colorectal cancer . Methods : Patients were drawn from a hospital registry of 2400 consecutive resections over the period 1995–2009 . Thirty-four potential predictors of prolonged ileus were analyzed by logistic regression . Results : Prolonged ileus occurred in 14.0 % of patients . Statistically significant independent predictors of prolonged ileus were male sex ( OR : 1.7 , P < 0.001 ) , peripheral vascular disease ( OR : 1.8 , P < 0.001 ) , respiratory comorbidity ( OR : 1.6 , P < 0.001 ) , resection at urgent operation ( OR : 2.2 , P < 0.001 ) , perioperative transfusion ( OR : 1.6 , P < 0.010 ) , stoma constructed ( OR : 1.4 , P < 0.001 ) , and operation lasting ≥3 hours ( OR : 1.6 , P < 0.001 ) . Conclusions : These features can be used to alert medical and nursing staff to patients likely to experience prolonged ileus after bowel resection so that they can be monitored closely in the postoperative period and available treatments targeted toward them . These features may also be useful in the research context to facilitate the more efficient selection of high-risk patients as subjects in clinical trials of prevention or treatment Objective : The aim of this trial was to investigate whether a routine of allowing normal food at will increases morbidity after major upper gastrointestinal ( GI ) surgery . Summary Background Data : Nil-by-mouth with enteral tube feeding is widely practice d for several days after major upper GI surgery . After other abdominal operations , normal food at will has been shown to be safe and to improve gut function . Methods : Patients were r and omly assigned to a routine of nil-by-mouth and enteral tube feeding by needle-catheter jejunostomy ( ETF group ) or normal food at will from the first day after major upper GI surgery . Primary end point was rate of major complications and death . Secondary outcomes were minor complications and adverse events , bowel function , and length of stay . All patients were invited to a follow-up at 8 weeks after discharge from the hospital . Results : Four hundred fifty-three patients who underwent major open upper GI surgery in 5 centers were enrolled between 2001 and 2006 . Four hundred forty-seven patients were correctly r and omized . Of 227 patients 76 ( 33.5 % ) had major complications in the ETF group compared with 62 ( 28.2 % ) of 220 patients allowed normal food at will ( P = 0.26 , 95 % CI for the difference in rate from −3.3 to 13.9 ) . In the ETF group , 36 ( 15.9 % ) patients were reoperated compared with 29 ( 13.2 % ) in the group allowed normal food at will ( P = 0.50 ) and 30-day mortality was 10 ( 4.4 % ) of 227 and 11 ( 5.0 % ) of 220 patients , respectively ( P = 0.83 ) . Time to resumed bowel function was significantly in favor of allowing normal food at will ( P = 0.01 ) , as were the total number of major Output:	The use of chewing gum after colorectal surgery is a safe and effective intervention in reducing the incidence of POI and merits routine use alongside other ERAS pathways in the postoperative setting
MS21819	*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: See related article , p 2509 Intra-arterial therapy ( IAT ) for acute ischemic stroke ( AIS ) has dramatically evolved during the past decade to include aspiration and stent-retriever devices . Recent r and omized controlled trials have demonstrated the superior revascularization efficacy of stent-retrievers compared with the first-generation Merci device.1,2 Additionally , the Diffusion and Perfusion Imaging Evaluation for Underst and ing Stroke Evolution ( DEFUSE ) 2 , the Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy ( MR RESCUE ) , and the Interventional Management of Stroke ( IMS ) III trials have confirmed the importance of early revascularization for achieving better clinical outcome .3–5 Despite these data , the current heterogeneity in cerebral angiographic revascularization grading ( CARG ) poses a major obstacle to further advances in stroke therapy . To date , several CARG scales have been used to measure the success of IAT.6–14 Even when the same scale is used in different studies , it is applied using varying operational criteria , which further confounds the interpretation of this key metric.10 The lack of a uniform grading approach limits comparison of revascularization rates across clinical trials and hinders the translation of promising , early phase angiographic results into proven , clinical ly effective treatments.6–14 For these reasons , it is critical that CARG scales be st and ardized and end points for successful revascularization be refined.6 This will lead to a greater underst and ing of the aspects of revascularization that are strongly predictive of clinical response . The optimal grading scale must demonstrate ( 1 ) a strong correlation with clinical outcome , ( 2 ) simplicity and feasibility of scale interpretation while ensuring characterization of relevant angiographic findings , and ( 3 ) high inter-rater reproducibility . To address these issues , a multidisciplinary panel of neurointerventionalists , neuroradiologists , and stroke neurologists with extensive experience in neuroimaging and IAT , convened at the “ Consensus Meeting on Revascularization Grading Following Endovascular Therapy ” with the goal Background and Purpose — The only Food and Drug Administration ( FDA ) -approved treatment for acute ischemic stroke is tissue plasminogen activator ( tPA ) given intravenously within 3 hours of symptom onset . An alternative strategy for opening intracranial vessels during stroke is mechanical embolectomy , especially for patients ineligible for intravenous tPA . Methods — We investigated the safety and efficacy of a novel embolectomy device ( Merci Retriever ) to open occluded intracranial large vessels within 8 hours of the onset of stroke symptoms in a prospect i ve , nonr and omized , multicenter trial . All patients were ineligible for intravenous tPA . Primary outcomes were recanalization and safety , and secondary outcomes were neurological outcome at 90 days in recanalized versus nonrecanalized patients . Results — Recanalization was achieved in 46 % ( 69/151 ) of patients on intention to treat analysis , and in 48 % ( 68/141 ) of patients in whom the device was deployed . This rate is significantly higher than that expected using an historical control of 18 % ( P<0.0001 ) . Clinical ly significant procedural complications occurred in 10 of 141 ( 7.1 % ) patients . Symptomatic intracranial hemorrhages was observed in 11 of 141 ( 7.8 % ) patients . Good neurological outcomes ( modified Rankin score ≤2 ) were more frequent at 90 days in patients with successful recanalization compared with patients with unsuccessful recanalization ( 46 % versus 10 % ; relative risk [ RR ] , 4.4 ; 95 % CI , 2.1 to 9.3 ; P<0.0001 ) , and mortality was less ( 32 % versus 54 % ; RR , 0.59 ; 95 % CI , 0.39 to 0.89 ; P=0.01 ) . Conclusions — A novel endovascular embolectomy device can significantly restore vascular patency during acute ischemic stroke within 8 hours of stroke symptom onset and provides an alternative intervention for patients who are otherwise ineligible for thrombolytics Background and Purpose — Desmoteplase is a novel plasminogen activator with favorable features in vitro compared with available agents . This study evaluated safety and efficacy of intravenous ( IV ) desmoteplase in patients with perfusion/diffusion mismatch on MRI 3 to 9 hours after onset of acute ischemic stroke . Methods — DEDAS was a placebo-controlled , double-blind , r and omized , dose-escalation study investigating doses of 90 & mgr;g/kg and 125 & mgr;g/kg desmoteplase . Eligibility criteria included baseline National Institute of Health Stroke Scale ( NIHSS ) scores of 4 to 20 and MRI evidence of perfusion/diffusion mismatch . The safety end point was the rate of symptomatic intracranial hemorrhage . Primary efficacy co-end points were MRI reperfusion 4 to 8 hours after treatment and good clinical outcome at 90 days . The primary analyses were intent-to-treat . Before unblinding , a target population , excluding patients violating specific MRI criteria , was defined . Results — Thirty-seven patients were r and omized and received treatment ( intent-to-treat ; placebo : n=8 ; 90 & mgr;g/kg : n=14 ; 125 & mgr;g/kg : n=15 ) . No symptomatic intracranial hemorrhage occurred . Reperfusion was achieved in 37.5 % ( 95 % CI [ 8.5 ; 75.5 ] ) of placebo patients , 18.2 % ( 2.3 ; 51.8 ) of patients treated with 90 & mgr;g/kg desmoteplase , and 53.3 % ( 26.6 ; 78.7 ) of patients treated with 125 & mgr;g/kg desmoteplase . Good clinical outcome at 90 days occurred in 25.0 % ( 3.2 ; 65.1 ) treated with placebo , 28.6 % ( 8.4 ; 58.1 ) treated with 90 & mgr;g/kg desmoteplase and 60.0 % ( 32.3 ; 83.7 ) treated with 125 & mgr;g/kg desmoteplase . In the target population ( n=25 ) , the difference compared with placebo increased and was statistically significant for good clinical outcome with 125 & mgr;g/kg desmoteplase ( P=0.022 ) . Conclusions — Treatment with IV desmoteplase 3 to 9 hours after ischemic stroke onset appears safe . At a dose of 125 & mgr;g/kg desmoteplase appeared to improve clinical outcome , especially in patients fulfilling all MRI criteria . The results of DEDAS generally support the results of its predecessor study , Desmoteplase in Acute Ischemic Stroke ( DIAS ) Background and Purpose — The Penumbra Pivotal Stroke Trial reported a 25 % good outcome ( modified Rankin scale score ≤2 ) despite an 81 % recanalization rate . We evaluated the association of a favorable initial noncontrast CT and a short time to recanalization in predicting good outcome . Methods — Data were from the Penumbra Pivotal Stroke Trial . Baseline scans were evaluated by 2 experienced readers blinded to outcomes using ASPECTS . ASPECTS scores were dichotomized into > 7 and ≤7 for primary analysis . Data on degree of recanalization based on thrombolysis in myocardial infa rct ion scores , stroke onset to recanalization , and CT to recanalization times were obtained . Primary outcome was modified Rankin scale score ≤2 at 3 months . Results — Median baseline NIHSS was 18 ( range , 8–34 ) and median baseline ASPECTS score was 6 ( range , 0–10 ) ; 81.2 % achieved recanalization ( thrombolysis in myocardial infa rct ion , 2–3 ) and ( 27.7 % ) achieved good outcome . Good outcome was significantly higher in the ASPECTS score > 7 group when compared to the ASPECTS score ≤7 group ( 50 % vs 15 % ; RR , 3.3 ; 95 % CI , 1.6–6.8 ; P=0.0001 ) . No patient with an ASPECTS score ≤4 ( n=28 ) or without recanalization ( n=16 ) had a good outcome . There was an interaction between baseline ASPECTS score ( > 7 and ≤7 ) and onset to recanalization time ( ≤300 minutes and > 300 minutes ) in predicting good outcome ( P=0.06 ) . Conclusion — Patients with baseline CT ASPECTS score ≤4 do not benefit from recanalization . Fast recanalization may benefit patients with evident damage on the CT scan ( ASPECTS score > 4 ) . Overall , patients benefit the most with early recanalization and a favorable baseline CT scan ( ASPECTS score > 7 ) Background and Purpose — The Middle Cerebral Artery Embolism Local Fibrinolytic Intervention Trial ( MELT ) Japan was organized to determine the safety and clinical efficacy of intraarterial infusion of urokinase ( UK ) in patients with stroke within 6 hours of onset . Methods — Patients with ischemic stroke presenting within 6 hours of onset and displaying occlusions of the M1 or M2 portion of the middle cerebral artery on carotid angiography were r and omized to the UK or control groups . Clinical outcome was assessed by the modified Rankin Scale , National Institutes of Health Stroke Scale , and Barthel Index . Results — The Independent Monitoring Committee recommended stopping the trial after approval of intravenous infusion of recombinant tissue plasminogen activator in Japan . A total of 114 patients underwent r and omization , 57 patients in each group . Background characteristics were comparable between the 2 groups . The primary end point of favorable outcome ( modified Rankin Scale 0 to 2 ) at 90 days was somewhat more frequent in the UK group than in the control group ( 49.1 % and 38.6 % , OR : 1.54 , 95 % CI : 0.73 to 3.23 ) but did not reach a significant level ( P=0.345 ) . However , excellent functional outcome ( modified Rankin Scale 0 to 1 ) at 90 days , a preplanned secondary end point , was more frequent in the UK group than in the control group ( 42.1 % and 22.8 % , P=0.045 , OR : 2.46 , 95 % CI : 1.09 to 5.54 ) . There were significantly more patients with National Institutes of Health Stroke Scale 0 or 1 at 90 days in the UK group than the control group ( P=0.017 ) . The 90-day cumulative mortality was 5.3 % in the UK group and 3.5 % in the control group ( P=1.000 ) , and intracerebral hemorrhage within 24 hours of treatment occurred in 9 % and 2 % , respectively ( P=0.206 ) . Conclusions — The trial was aborted prematurely and the primary end point did not reach statistical significance . Nevertheless , the secondary analyses suggested that intraarterial fibrinolysis has the potential to increase the likelihood of excellent functional outcome BACKGROUND Trials of endovascular therapy for ischemic stroke have produced variable results . We conducted this study to test whether more advanced imaging selection , recently developed devices , and earlier intervention improve outcomes . METHODS We r and omly assigned patients with ischemic stroke who were receiving 0.9 mg of alteplase per kilogram of body weight less than 4.5 hours after the onset of ischemic stroke either to undergo endovascular thrombectomy with the Solitaire FR ( Flow Restoration ) stent retriever or to continue receiving alteplase alone . All the patients had occlusion of the internal carotid or middle cerebral artery and evidence of salvageable brain tissue and ischemic core of less than 70 ml on computed tomographic ( CT ) perfusion imaging . The co primary outcomes were reperfusion at 24 hours and early neurologic improvement ( ≥8-point reduction on the National Institutes of Health Stroke Scale or a score of 0 or 1 at day 3 ) . Secondary outcomes included the functional score on the modified Rankin scale at 90 days . RESULTS The trial was stopped early because of efficacy after 70 patients had undergone r and omization ( 35 patients in each group ) . The percentage of ischemic territory that had undergone reperfusion at 24 hours was greater in the endovascular-therapy group than in the alteplase-only group ( median , 100 % vs. 37 % ; P<0.001 ) . Endovascular therapy , initiated at a median of 210 minutes after the onset of stroke , increased early neurologic improvement at 3 days ( 80 % vs. 37 % , P=0.002 ) and improved the functional outcome at 90 days , with more patients achieving functional independence ( score of 0 to 2 on the modified Rankin scale , 71 % vs. 40 % ; P=0.01 ) . There were no significant differences in rates of death or symptomatic intracerebral hemorrhage . CONCLUSIONS In patients with ischemic stroke with a proximal cerebral arterial occlusion and salvageable tissue on CT perfusion imaging , early thrombectomy with the Solitaire FR stent retriever Output:	FINDINGS Intravenous thrombolysis is the mainstay of acute ischemic stroke management for any patient with disabling deficits presenting within 4.5 hours from symptom onset . R and omized trials have demonstrated that more patients return to having good function ( defined by being independent and having slight disability or less ) when treated within 4.5 hours after symptom onset with intravenous recombinant tissue plasminogen activator ( IV rtPA ) therapy . Regardless of mode of reperfusion , earlier reperfusion is associated with better clinical outcomes . AND RELEVANCE Intravenous rtPA remains the st and ard of care for patients with moderate to severe neurological deficits who present within 4.5 hours of symptom onset . Outcomes for some patients with acute ischemic stroke and moderate to severe neurological deficits due to proximal artery occlusion are improved with endovascular reperfusion therapy .
MS21820	*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: Functional variables after coloanal anastomosis or anastomosis with J pouch were investigated in 40 patients in a prospect i ve r and omized study . Continence for liquids and gas control were superior after J pouch anastomosis compared with coloanal reconstruction . The neorectal capacity was higher after J pouch anastomosis . The perception threshold for stool filling was higher in patients with J pouch resembling those values observed preoperatively . Quality of life was improved in subjects with with J pouch , although differences did not reach a significant level Objective To assess the efficacy of a novel coloplasty colonic pouch design in optimizing bowel function after ultralow anterior resection . Summary Background Data A colonic J-pouch may reduce excessive stool frequency and incontinence after anterior resection , but at the risk of evacuation problems . Experimental surgery on pigs has suggested that a coloplasty pouch ( CP ) may be a useful alternative . Although CP has recently been shown to be feasible in patients , there is no r and omized controlled trial comparing bowel function with the J-pouch . Methods After anterior resection for cancer , patients were allocated to either J-pouch or CP-anal anastomoses . Continence scoring , anorectal manometry , and endoanal ultrasound assessment s were made before surgery . All complications were recorded , and these preoperative assessment s were repeated at 4 months . The assessment s were repeated again at 1 year , and a quality of life question naire was added . Results Eighty-eight patients were recruited from October 1998 to April 2000 . Both groups were well matched for age , gender , staging , adjuvant therapy , and mean follow-up . There were no differences in the intraoperative time and hospital stay . CP result ed in more anastomotic leaks . At 4 months , J-pouch patients had 10.3 % less stool fragmentation but poorer stool deferment and more nocturnal leakage . However , there were no differences in the bowel function , continence score , and quality of life at 1 year . There were no differences in the anorectal manometry and endoanal ultrasound findings . Conclusions Coloplasty pouches result ed in more anastomotic leaks and minimal differences in bowel function . At present , the J-pouch remains the benchmark for routine clinical practice , and due care ( including defunctioning stoma ) should be exercised in situations requiring CP Objectives To compare a colonic J-pouch or a side-to-end anastomosis after low-anterior resection for rectal cancer with regard to functional and surgical outcome . Summary Background Data A complication after restorative rectal surgery with a straight anastomosis is low-anterior resection syndrome with a postoperatively deteriorated anorectal function . The colonic J-reservoir is sometimes used with the purpose of reducing these symptoms . An alternative method is to use a simple side-to-end anastomosis . Methods One-hundred patients with rectal cancer undergoing total mesorectal excision and colo-anal anastomosis were r and omized to receive either a colonic pouch or a side-to-end anastomosis using the descending colon . Surgical results and complications were recorded . Patients were followed with a functional evaluation at 6 and 12 months postoperatively . Results Fifty patients were r and omized to each group . Patient characteristics in both groups were very similar regarding age , gender , tumor level , and Dukes ’ stages . A large proportion of the patients received short-term preoperative radiotherapy ( 78 % ) . There was no significant difference in surgical outcome between the 2 techniques with respect to anastomotic height ( 4 cm ) , perioperative blood loss ( 500 ml ) , hospital stay ( 11 days ) , postoperative complications , reoperations or pelvic sepsis rates . Comparing functional results in the 2 study groups , only the ability to evacuate the bowel in < 15 minutes at 6 months reached a significant difference in favor of the pouch procedure . Conclusions The data from this study show that either a colonic J-pouch or a side-to-end anastomosis performed on the descending colon in low-anterior resection with total mesorectal excision are methods that can be used with similar expected functional and surgical results A system has been constructed to evaluate the design , implementation , and analysis of r and omized control trials ( RCT ) . The degree of quadruple blinding ( the r and omization process , the physicians and patients as to therapy , and the physicians as to ongoing results ) is considered to be the most important aspect of any trial . The analytic techniques are scored with the same emphasis as is placed on the control of bias in the planning and implementation of the studies . Description of the patient and treatment material s and the measurement of various controls of quality have less weight . An index of quality of a RCT is proposed with its pros and cons . If published papers were to approximate these principles , there would be a marked improvement in the quality of r and omized control trials . Finally , a reasonable st and ard design and conduct of trials will facilitate the interpretation of those with conflicting results and help in making valid combinations of undersized trials Background : Total mesorectal excision ( TME ) and colonic J pouch reconstruction has been widely practice d for mid- or low-rectal cancer . However , the laparoscopic version of TME has never been described . Methods : Five patients suffering from newly diagnosed mid- to low-rectal cancer were seen between March and July 1999 . These five patients were selected for laparoscopic TME and colonic J pouch reconstruction because preoperative investigations revealed resectable tumor without extrarectal disease . Results : There were three men and two women with a mean age of 61 years . The average body weight was 69 kg ( range , 57 - 80 ) . None of the patients had had previous abdominal operations . In all five patients , the tumor was located within 9 cm from anal verge . The average size of the main incision was 5 cm . All patients had a covering ileostomy at the end of the procedure . The mean operating time was 208 min ; average blood loss was 158 ml ; and mean hospital stay was 10.6 days . Three patients had Dukes ' B disease and two had Dukes ' C disease . The resection margins ( proximal , circumferential , and distal ) were all clear . There were no deaths or major complications . Two patients suffered from transient urinary retention . After ileostomy closure , the median frequency of bowel motion was twice per day at 6-month follow-up . Neither incontinence nor nocturnal soiling was reported . Conclusion : To the best of our knowledge , this is the first published series of such an operation . With good patient selection , laparoscopic-assisted TME and colonic J pouch-anal anastomosis is safe and feasible The efficacy of colon-J-pouch anal anastomosis ( CPAA ) in reducing defecatory frequency and urgency and the incidence of anastomotic fistulas has been proved by several studies but only as compared to straight colo-anal anastomosis ( CAA ) of the end-to-end type . We investigated the role played by the colon pouch in the strict sense , without the influence of a different CAA model , in a r and omised prospect i ve study comparing CPAA and straight side-to-end CAA . Over the period from 1994 to 1998 we selected 66 of 118 patients operated on for rectal cancer : a CPAA was constructed in 35 ( group P ) and a direct side-to-end CAA in 31 ( group D ) . The two groups were well matched for surgeon , type of patient , stage of disease and incidence of radiotherapy and presented no differences in operative mortality , general and anastomotic morbidity , or need for reoperation . Functional results : after 3 , 12 and 36 months , defecatory frequency > or = 4 movements/day was observed in 93.4 , 67.7 and 41.6 % of cases , respectively , in group D as against 25.7 , 14.2 and 13 % , respectively , in group P ( P < 0.05 ) , while defecatory urgency was recorded in 77.4 , 35.4 and 27.9 % of cases , respectively , in group D as against 34.2 , 17.1 and 9 % , respectively , in group P ( p < 0.05 ) . In the long term , incontinence was also significantly lower in group P. The colon pouch improves sphincter rehabilitation after anal recanalization compared to straight side-to-end CAA . It does not affect anastomotic morbidity but affords a protective effect on function in irradiated patients . CPAA proves to be the optimal reconstruction option after excision of the rectum Introduction : Colonic pouches have been used for 20 years to provide reservoir function after reconstructive proctectomy for rectal cancer . More recently coloplasty has been advocated as an alternative to a colonic pouch . However there have been no long-term r and omized , controlled trials to compare functional outcomes of coloplasty , colonic J-Pouch ( JP ) , or a straight anastomosis ( SA ) after the treatment of low rectal cancer . Aim : To compare the complications , long-term functional outcome , and quality of life ( QOL ) of patients undergoing a coloplasty , JP , or an SA in reconstruction of the lower gastrointestinal tract after proctectomy for low rectal cancer . Methods : A multicenter study enrolled patients with low rectal cancer , who were r and omized intraoperatively to coloplasty ( CP-1 ) or SA if JP was not feasible , or JP or coloplasty ( CP-2 ) if a JP was feasible . Patients were followed for 24 months with SF-36 surveys to evaluate the QOL . Bowel function was measured quantitatively and using Fecal Incontinence Severity Index ( FISI ) . Urinary function and sexual function were also assessed . Results : Three hundred sixty-four patients were r and omized . All patients were evaluated for complications and recurrence . Mean age was 60 ±12 years , 71 % were male . Twenty-three ( 7.4 % ) died within 24 months of surgery . No significant difference was observed in the complications among the 4 groups . Two hundred ninety-seven of 364 were evaluated for functional outcome at 24 months . There was no difference in bowel function between the CP-1 and SA groups . JP patients had fewer bowel movements , less clustering , used fewer pads and had a lower FISI than the CP-2 group . Other parameters were not statistically different . QOL scores at 24 months were similar for each of the 4 groups . Conclusions : In patients undergoing a restorative resection for low rectal cancer , a colonic JP offers significant advantages in function over an SA or a coloplasty . In patients who can not have a pouch , coloplasty seems not to improve the bowel function of patients over that with an SA PURPOSE : The colonic J-pouch anastomosis has been advocated to obviate urgent and frequent defecations following a sphincter-saving rectal excision . Physiologic characteristics of the colonic J-pouch were compared with those of the traditional straight anastomosis and related to clinical function . METHOD : Patients with total mesorectal excision for carcinoma were r and omized to either a straight ( n=23 ) or a colonic pouch anastomosis ( n=23 ) . The patients were examined before and at one year after surgery ( n=42 ) , which included laboratory studies , and a question naire regarding anorectal function was completed . RESULTS : Preoperative compliance of the rectum was restored after surgery in the pouch group , 2.9 ( 2.2–3.4 ) ml/cm H2O , but there was a significant decrease after surgery in the straight anastomosis group , 1.9 (1.1–2.3)P<0.001 ( median ( interquartile range ) ) . Sphincter pressures in both groups were similar . In a multiple regression analysis , high compliance was associated with favorable clinical function , and hypermotility of the anal canal was associated with adverse clinical function . CONCLUSIONS : Colonic pouch-anal anastomosis restores neorectal compliance , which is important for good function after low anterior resection . Presence of an unstable internal sphincter is a negative factor for clinical function in both straight and pouch anastomoses PURPOSE : Colonic pouches have gained increasing popularity in reconstruction after low anterior resection . In this prospect i ve , r and omized trial colonic pouch reconstruction is compared with side-to-end anastomosis for functional outcome . METHODS : From October 1995 to October 1996 , 29 patients had colonic pouch and 30 patients had side-to-end anastomosis reconstruction after low anterior resection . Patients were matched for age , gender , and tumor stage and localization . All patients underwent functional evaluation preoperatively and at three and six months post-operatively . RESULTS : There was no difference in preoperative anorectal function . The operating time was higher in the colonic pouch group ( 167vs . 149 minutes ) . Twenty-three patients ( 79.3 percent ) with colonic pouch had a protective stoma compared with 21 patients ( 70 percent ) with side-to-end anastomosis . Postoperative complications were 10.3 and 13.3 percent , respectively . There was no difference in manometric pressure of the anus , in anorectal angle , and in continence status after three and six months . Stool frequency was higher in the side-to-end anastomosis group , with 2.2vs . 5.4 per day at three months and 2.3vs . 3.1 per day at six months . Constipation was noted in two patients with colonic pouch ( 7 percent ) and none in the side-to-end anastomosis group at three months and twovs . none at six months . Maximum tolerated volume and threshold volume was higher in the colonic pouch group at three and at six months . CONCLUSION : Both forms of reconstruction have similar satisf Output:	Conclusions J-pouch or STEA are acceptable and safe options after AR for rectal cancer .
MS21821	*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 Variability in patients ' response to interventions in pain and other clinical setting s is large . Many explanations such as trial methods , environment or culture have been proposed , but this paper sets out to show that the main cause of the variability may be r and om chance , and that if trials are small their estimate of magnitude of effect may be incorrect , simply because of the r and om play of chance . This is highly relevant to the questions of ‘ How large do trials have to be for statistical accuracy ? ’ and ‘ How large do trials have to be for their results to be clinical ly valid ? ’ The true underlying control event rate ( CER ) and experimental event rate ( EER ) were determined from single‐dose acute pain analgesic trials in over 5000 patients . Trial group size required to obtain statistically significant and clinical ly relevant ( 0.95 probability of number‐needed‐to‐treat within ±0.5 of its true value ) results were computed using these values . Ten thous and trials using these CER and EER values were simulated using varying group sizes to investigate the variation due to r and om chance alone . Most common analgesics have EERs in the range 0.4–0.6 and CER of about 0.19 . With such efficacy , to have a 90 % chance of obtaining a statistically significant result in the correct direction requires group sizes in the range 30–60 . For clinical relevance nearly 500 patients are required in each group . Only with an extremely effective drug ( EER>0.8 ) will we be reasonably sure of obtaining a clinical ly relevant NNT with commonly used group sizes of around 40 patients per treatment arm . The simulated trials showed substantial variation in CER and EER , with the probability of obtaining the correct values improving as group size increased . We contend that much of the variability in control and experimental event rates is due to r and om chance alone . Single small trials are unlikely to be correct . If we want to be sure of getting correct ( clinical ly relevant ) results in clinical trials we must study more patients . Credible estimates of clinical efficacy are only likely to come from large trials or from pooling multiple trials of conventional ( small ) size Forty to 78 % of the patients using sumatriptan for the acute treatment of migraine may present recurrence at least occasionally . The concomitant use of a NSAID ( nonsteroidal anti-inflammatory drug ) has been recommended to decrease the recurrence rate . Sixty seven patients that treated successfully 8 migraine attacks with 100 mg of sumatritpan PO and presented recurrence in at least 5 attacks were studied prospect ively . The patients received 100 mg of sumatriptan and 550 mg of naproxen sodium PO to treat 4 consecutive moderate or severe migraine attacks . The recurrence rate , once at least 62.5 % ( 5 out of 8 attacks ) , decreased to 14.2 % ( 38 out of 268 attacks ) with the combination of compounds ( p<0.0001 ) . We then studied two groups of 13 patients made r and omicaly from the 67 initially evaluated , that were given sumatriptan 100 mg plus naproxen sodium 550 mg or placebo , in a double-blind design , to treat 3 other consecutive migraine attacks . Each group of patients treated 39 attacks . The recurrence among the patients taking sumatriptan plus placebo was 59 % ( 23 out of 39 attacks ) and the recurrence presented by the group taking sumatriptan plus naproxen was 25.5 % ( 10 out of 39 attacks ) ( p<0.0003 ) . We concluded that the combination of sumatriptan plus naproxen sodium decreases significantly migraine recurrence presented by patients taking sumatriptan alone Objective Probable migraine is a common , disabling migraine subtype fulfilling all but one of the diagnostic criteria for migraine . This study was conducted to evaluate the efficacy and tolerability of sumatriptan/naproxen sodium for the acute treatment of probable migraine without aura . Methods Patients treated a headache of probable migraine without aura when pain was moderate or severe with sumatriptan/naproxen sodium ( n = 222 intent-to-treat ( ITT ) ) or placebo ( n = 221 ITT/complete case analysis a ) in this r and omized , double-blind , parallel-group study . Results Sumatriptan/naproxen sodium was more effective than placebo with respect to the co- primary efficacy endpoints two-hour pain-free response ( 29 % sumatriptan/naproxen sodium vs 11 % placebo , p < 0.001 ) and two- to 24-hour sustained pain-free response ( 24 % sumatriptan/naproxen sodium vs 9 % placebo , p < 0.001 ) . Sumatriptan/naproxen sodium was significantly more effective than placebo with respect to the secondary efficacy endpoints of pain-free response four hours postdose ( p < 0.001 ) , pain-free response maintained one to two hours postdose ( p = 0.034 ) and two to four hours postdose ( p < 0.001 ) , headache relief four hours postdose ( p < 0.001 ) , headache relief maintained two to four hours postdose ( p = 0.015 ) , sustained headache relief two through 24 hours postdose ( p = 0.002 ) , and rescue medication use ( p < 0.001 ) ; but not productivity scores . The most common adverse events were dizziness ( 4 % sumatriptan/naproxen sodium,<1 % placebo ) , dry mouth ( 2 % sumatriptan/naproxen sodium , < 1 % placebo ) , and nausea ( 2 % sumatriptan/naproxen sodium , < 1 % placebo ) . Conclusion Sumatriptan/naproxen sodium is effective in the acute treatment of probable migraine as demonstrated by higher rates of freedom from pain and restoration of function Objective : To estimate the 1-year prevalences of primary headache disorders and identify their principal risk factors in the general population of Russia . Methods : A countrywide population -based r and om sample of 2725 biologically unrelated adults in 35 cities and nine rural areas were interviewed in a door-to-door survey using a previously vali date d diagnostic question naire . Results : Of the 2725 eligible adults contacted , 2025 ( 74.3 % ) responded ( females 52.6 % , mean age 39.5 ± 13.4 years ) . Of these , 1273 ( 62.9 % ) reported headache ‘ not related to flu , hangover , cold , head injury ’ occurring at least once in the previous year . The gender- and age-st and ardized 1-year prevalence of migraine was 20.8 % . Female gender ( odds ratio ( OR ) = 3.8 ; 95 % confidence interval ( CI ) 2.8–5.1 ) and obesity ( OR = 1.5 ; 1.1–2.1 ) were positively associated with this type of headache . The gender- and age-st and ardized 1-year prevalence of tension-type headache ( TTH ) was 30.8 % . TTH was more prevalent in urban than in rural areas ( OR = 1.6 ; 1.3–2.0 ) . Headache on ≥15 days/month was reported by 213 ( 10.5 % ) respondents ( gender- and age-st and ardized prevalence 10.4 % ) , and associated with low socioeconomic status ( OR = 3.4 ; 2.4–4.9 ) , obesity ( OR = 3.0 ; 2.1–4.3 ) , female gender ( OR = 2.9 ; 2.1–4.1 ) and age over 40 years ( OR = 2.6 ; 1.9–3.6 ) . The majority of these respondents ( 68.1 % ) overused acute headache medications . Conclusion : The study demonstrated a high prevalence of migraine and a very high prevalence of headache on ≥15 days/month , and revealed unmet health-care needs of people with headache in Russia OBJECTIVES To evaluate the long-term safety and tolerability of sumatriptan-naproxen sodium for the treatment of moderate to severe acute migraines and to assess the safety of administration of an optional second dose . PATIENTS AND METHODS A 12-month , multicenter , open-label safety study was conducted in adults treated for migraine attacks of moderate to severe intensity from April 14 , 2004 , to August 18 , 2005 . Safety evaluations included adverse events and laboratory tests . RESULTS Of 600 patients enrolled , 565 ( 94 % ) were treated for at least 1 migraine . Of treated patients , 414 ( 73 % ) and 362 ( 64 % ) completed 6 and 12 months of treatment , respectively . Of the 24,485 attacks treated , 17,144 ( 70 % ) were treated with only 1 dose . On average , patients treated 5 migraine attacks per month , with a median of 6 days between attacks . The most common treatment-related adverse events were nausea , muscle tightness , and dizziness . Fourteen patients reported 1 or more serious adverse event with only 1 judged probably related to treatment . No deaths occurred . Eight percent of patients discontinued participation in the study because of adverse events or pregnancy . The rates of adverse events reported were no higher after treatment with 2 tablets ( at least 2 hours apart ) compared with 1 tablet . CONCLUSIONS In this 12-month data set of more than 24,000 migraine attacks in 565 patients , sumatriptan-naproxen sodium formulated in a single tablet was well tolerated when used episodically for the treatment of acute migraine . The adverse events did not differ from those expected for the individual components alone , and no new or unexpected findings occurred OBJECTIVE To describe return to normal function , productivity , and satisfaction of patients with moderate or severe migraine attacks treated with combined sumatriptan/naproxen sodium , sumatriptan alone , naproxen sodium alone , or placebo . PATIENTS , DESIGN , AND SETTING Patients in 2 identical , US , phase 3 , r and omized , double-blind , parallel-group , placebo-controlled , single-dose , multicenter studies treated a single moderate or severe migraine attack with sumatriptan/naproxen sodium ( 85 mg sumatriptan formulated with RT Technology and 500 mg naproxen sodium in a single-tablet formulation ) , sumatriptan , naproxen sodium , or placebo . MAIN OUTCOME MEASURES Ability to function ( not impaired , mildly impaired , severely impaired , or required bed rest ) was collected in diary cards completed immediately prior to treatment , every 30 minutes for the first 2 hours , and hourly from 2 to 24 hours while awake . Patients completed the Productivity Assessment Question naire ( PAQ ) 24 hours after study drug administration . The Patient Perception of Migraine Question naire ( PPMQ ) was administered at screening and 24 hours post treatment to capture patient satisfaction . RESULTS Compared with the other groups , the sumatriptan/naproxen sodium group reported significantly higher levels of normal or mildly impaired functioning as early as 2 and 4 hours after dosing . They also demonstrated greater reductions in workplace productivity loss compared with placebo in both studies , and were consistently more satisfied with their treatment compared with patients in other treatment groups and compared with their usual medications . CONCLUSIONS Treatment with sumatriptan/naproxen sodium allowed significantly more subjects to return to normal or mildly impaired functioning more quickly , and sumatriptan/naproxen sodium patients were significantly more satisfied with their treatment compared with other treatment groups . Overall productivity loss was significantly reduced following use of sumatriptan/naproxen sodium CONTEXT Multiple pathogenic mechanisms may be involved in generating the migraine symptom complex , and multimechanism-targeted therapy may confer advantages over monotherapy . OBJECTIVE To evaluate the efficacy and safety of a fixed-dose tablet containing sumatriptan succinate and naproxen sodium relative to efficacy and safety of each monotherapy and placebo for the acute treatment of migraine . DESIGN , SETTING , AND PARTICIPANTS Two replicate , r and omized , double-blind , single-attack , parallel-group studies conducted among 1461 ( study 1 ) and 1495 ( study 2 ) patients at 118 US clinical centers who were diagnosed as having migraine and received study treatment for a moderate or severe migraine attack . INTERVENTIONS Patients were r and omized in a 1:1:1:1 ratio to receive a single tablet containing sumatriptan , 85 mg , and naproxen sodium , 500 mg ; sumatriptan , 85 mg ( monotherapy ) ; naproxen sodium , 500 mg ( monotherapy ) ; or placebo , to be used after onset of a migraine with moderate to severe pain . MAIN OUTCOME MEASURES Primary outcome measures included the percentages of patients with headache relief 2 hours after dosing , absence of photophobia , absence of phonophobia , and absence of nausea for the comparison between sumatriptan-naproxen sodium and placebo , and the percentages of patients with sustained pain-free response for the comparison between sumatriptan-naproxen sodium and each monotherapy . RESULTS Sumatriptan-naproxen sodium was more effective than placebo for headache relief at 2 hours after dosing ( study 1 , 65 % vs 28 % ; P<.001 and study 2 , 57 % vs 29 % ; P<. Output:	Overall , the combination was better than placebo for the primary outcomes of pain-free and headache relief at two hours . Using 50 mg of sumatriptan , rather than 85 mg , in the combination did not significantly change the result . Treating early , when pain was still mild , was significantly better than treating once pain was moderate or severe for pain-free responses at two hours and during the 24 hours post dose . Adverse events were mostly mild or moderate in severity and rarely led to withdrawal ; they were more common with the combination than with placebo ( moderate quality evidence ) .Where the data allowed direct comparison , combination treatment was superior to either monotherapy , but adverse events were less frequent with naproxen than with sumatriptan ( moderate quality evidence ) . Combination treatment was effective in the acute treatment of migraine headaches . The effect was greater than for the same dose of either sumatriptan or naproxen alone , but additional benefits over sumatriptan alone were not large . More participants achieved good relief when medication was taken early in the attack , when pain was still mild . Adverse events were more common with the combination and sumatriptan alone than with placebo or naproxen alone
MS21822	*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 Recombinant FSH ( rFSH ) is the current st and ard treatment for ovulation induction in women with polycystic ovary syndrome ( PCOS ) that do not respond to clomiphene citrate . Ovulation induction with rFSH is known to be costly due to the necessity of daily injections and intensive monitoring . An alternative strategy , starting with electrocautery of the ovaries , may be a less costly option . METHODS An economic evaluation was set up alongside a multicentre r and omized clinical trial comparing laparoscopic electrocautery of the ovaries , followed by clomiphene citrate and rFSH when anovulation persisted , and treatment with rFSH in 168 women with clomiphene citrate-resistant PCOS . Data on re sources used for treatment and productivity loss were collected prospect ively up to an eventual ongoing pregnancy with a time horizon of 12 months . RESULTS At 12 months the ongoing pregnancy rates were 67 % for both the electrocautery strategy and rFSH treatment . Mean total costs per woman were 5308 euros for the electrocautery strategy and 5925 euros for treatment with rFSH , result ing in a mean difference of 617 ( 95 % CI : -382 euros to 1614 euros ) . CONCLUSIONS The total treatment costs up to an ongoing pregnancy are comparable for rFSH treatment and an alternative strategy starting with electrocautery . Due to a lower number of multiple pregnancies , the electrocautery strategy can be expected to result in lower total costs when costs of the delivery are included STUDY OBJECTIVE To analyze the efficacy of laparoscopic ovarian drilling using monopolar diathermy in women with anovulatory infertility with clomiphene-resistant polycystic ovary syndrome ( PCOS ) , and to determine factors influencing pregnancy rate and pregnancy outcomes . DESIGN Prospect i ve study ( Canadian Task Force classification II-2 ) . SETTING Infertility clinic in a tertiary referral teaching hospital . PATIENTS Seventy women with clomiphene-resistant PCOS . INTERVENTION Laparoscopic ovarian drilling , with follow-up for 4.5 years . MEASUREMENTS AND MAIN RESULTS Follow-up data , which were available for 66 patients , showed a spontaneous ovulation rate of 81.8 % , cumulative ovulation rate of 93.9 % , and pregnancy rate of 54.5 % . Successful pregnancies were commonly complicated by gestational diabetes mellitus and pregnancy-induced hypertension . Pregnancy rates ( 23.5 % ) were low in women with tuboperitoneal disease and those whose partners had subfertile male factors . Statistical evaluation using a proportion test ( Z test ) and multivariable logistical regression analysis showed that elevated luteinizing hormone levels ( > 10 IU/L ) , short duration of infertility ( <3 yrs ) , and absence of preexisting tubal disease were associated with better outcomes . CONCLUSION Laparoscopic ovarian drilling is an effective surgical procedure in women with clomiphene-resistant PCOS OBJECTIVE This study aim ed to compare two methods of treatment of infertility with gonadotropin with laparoscopic ovarian electrocauterization in patients with clomiphene citrate-resistant polycystic ovary syndrome ( PCOS ) . METHODS A number of 104 nulipara patients with polycystic ovary syndrome , who were resistant to clomiphene citrate were r and omly assigned to two groups . One group received gonadotropin ; after the bleeding withdrawal and from the third day of the cycle , the injection of human menopausal gonadotropin ( HMG ) was started with 10 mg medroxy progesterone . The patients were followed with serial trans-vaginal sonographies . When the diameter of follicles reached to 18 mm , human chorionic gonadotropin ( HCG ) was prescribed . The other group was treated with laparoscopic ovarian electrocauterization under general anesthesia . If after 3 cycles , the anovulation was established with progesterone measurement , the clomiphene citrate was prescribed . Gonadotropin was administered , if the lack of ovulation persisted . RESULTS No significant difference was documented between the two groups in terms of the obesity indexes , duration of infertility , age , sonographic and laboratory findings . In the gonadotropin group , 37 cases ( 71 % ) of pregnancy occurred . The rate of pregnancy was the same in the other group consisting of 18 cases treated by electrocautery , 9 cases with cautery + clomiphene , and 10 cases with clomiphene + cautery + gonadotropin . In the group treated with gonadotropin , there were 1 triple and 4 twins pregnancies . In the group treated with ovarian electrocautery , one twin pregnancy was observed . In the group treated with gonadotropin , 2 cases of ovarian hyperstimulation syndrome , 1 case of ectopic pregnancy and 6 cases of miscarriage occurred ; the corresponding figure in the ovarian electrocautery group consisted of 5 cases of miscarriage . CONCLUSION Our findings suggest that ovarian electrocauterization is an appropriate method with good efficacy and low complication rate for infertility treatment of women with clomiphene citrate-resistant polycystic ovary syndrome BACKGROUND Long-term effects of laparoscopic electrocautery of the ovaries are unknown . To study the long-term effects of laparoscopic electrocautery of the ovaries and gonadotrophins , we followed women with clomiphene-resistant polycystic ovary syndrome ( PCOS ) r and omly allocated to one of these treatments until 8 - 12 years after their initial treatment . METHODS Between February 1998 and October 2001 168 women with clomiphene citrate-resistant PCOS were included in a r and omized controlled trial comparing an electrocautery strategy to a strategy starting with rFSH . In 2009 these women were contacted about their reproductive outcome and menstrual cycle regularity . Analysis was by intention-to-treat . We compared time to conception result ing in live birth , subsequent pregnancies , ectopic and multiple pregnancies , menopause , as well as minimal and maximal menstrual cycle length . RESULTS After 8 - 12 years , the cumulative proportion of women with a first child was 86 % in women who had been allocated to electrocautery versus 81 % in women who had been allocated to immediate rFSH [ relative ratio ( RR ) : 1.1 ; 95 % confidence interval ( CI ) : 0.92 - 1.2 ] . Treatment with electrocautery result ed in a significantly lower need for stimulated cycles to reach a live birth ; 53 % after electrocautery versus 76 % after rFSH ( RR : 0.69 ; 95 % CI : 0.55 - 0.88).The cumulative proportion of women with a second child was 61 % after electrocautery versus 46 % after immediate rFSH ( RR : 1.4 ; 95 % CI : 1.00 - 1.9 ) . Overall , there were 7 twins out of 134 deliveries ( 5 % ) after electrocautery versus 10 twins out of 124 deliveries ( 8 % ) in the rFSH group ( RR : 0.65 ; 95 % CI : 0.25 - 1.6 ) . Fifty-four per cent of the women allocated to electrocautery had a regular menstrual cycle 8 - 12 years after r and omization versus 36 % in those allocated to rFSH ( RR : 1.5 ; 95 % CI : 0.87 - 2.6 ) . CONCLUSION In women with clomiphene-resistant PCOS , laparoscopic electrocautery of the ovaries is as effective as ovulation induction with FSH treatment in terms of live births , but reduces the need for ovulation induction or ART in a significantly higher proportion of women and increases the chance for a second child . Clinicians may use these data when informing clomiphene-resistant anovulatory women about treatment options Abstract Objective To compare the effectiveness of an electrocautery strategy with ovulation induction using recombinant follicle stimulating hormone in patients with polycystic ovary syndrome . Design R and omised controlled trial . Setting Secondary and tertiary hospitals in the Netherl and s. Participants 168 patients with clomiphene citrate resistant polycystic ovary syndrome : 83 were allocated electrocautery and 85 were allocated recombinant follicle stimulating hormone . Intervention Laparoscopic electrocautery of the ovaries followed by clomiphene citrate and recombinant follicle stimulating hormone if anovulation persisted , or induction of ovulation with recombinant follicle stimulating hormone . Main outcome measure Ongoing pregnancy within 12 months . Results . The cumulative rate of ongoing pregnancy after recombinant follicle stimulating hormone was 67 % . With only electrocautery it was 34 % , which increased to 49 % after clomiphene citrate was given . Subsequent recombinant follicle stimulating hormone increased the rate to 67 % at 12 months ( rate ratio 1.01 , 95 % confidence interval 0.81 to 1.24 ) . No complications occurred from electrocautery with or without clomiphene citrate . Patients allocated to electrocautery had a significantly lower risk of multiple pregnancy ( 0.11 , 0.01 to 0.86 ) . Conclusion The ongoing pregnancy rate from ovulation induction with laparoscopic electrocautery followed by clomiphene citrate and recombinant follicle stimulating hormone if anovulation persisted , or recombinant follicle stimulating hormone , seems equivalent to ovulation induction with recombinant follicle stimulating hormone , but the former procedure carries a lower risk of multiple pregnancy BACKGROUND Ovulation induction with gonadotrophins is the st and ard treatment strategy for women with clomiphene citrate (CC)-resistant polycystic ovary syndrome ( PCOS ) . Laparoscopic electrocautery of the ovaries is an alternative treatment modality , leading to a comparable cumulative pregnancy rate . In deciding which treatment to opt for , women 's health-related quality of life ( HRQoL ) should be taken into account . METHODS A total of 168 CC-resistant women with PCOS were r and omly assigned to receive either the electrocautery strategy , entailing laparoscopic electrocautery of the ovaries followed by CC and recombinant FSH ( rFSH ) if anovulation persisted , or ovulation induction with rFSH . We assessed women 's HRQoL with the st and ard question naires Short Form-36 , Rotterdam Symptom Checklist and Center for Epidemiological Studies Depression Scale , administered before r and omization and 2 , 12 and 24 weeks thereafter . RESULTS The intention to treat analysis revealed no significant differences between the treatment groups on any of the scales at any point during follow-up . In women without an ongoing pregnancy , those treated with rFSH showed significantly more depressive symptoms than women allocated to the electrocautery strategy , with or without CC , although differences were small . CONCLUSIONS Overall , HRQoL was not affected in both groups . In women still under treatment , rFSH was slightly more burdensome for women 's HRQoL than electrocautery with or without CC This prospect i ve , r and omized study included 18 polycystic ovarian syndrome ( PCOS ) patients with severe ovarian dysfunction , who were evaluated by st and ard clomiphene and FSH stimulation . In this group of patients , a 6 month down-regulation with gonadotrophin-releasing hormone ( GnRH ) analogues gave outcomes similar to laparoscopic ovarian laser diathermy with respect to stimulatory outcome and pregnancy rate . Clomiphene stimulation with 50 mg of clomiphene/day and FSH stimulation in a low-dose , step-up protocol with purified FSH did not result in oligofollicular development ; thus patients were divided into two subgroups : one subgroup received laparoscopic laser drilling and the other received 6 months of therapy with GnRH analogues plus add-back therapy after diagnostic laparoscopy . Subsequently , three cycles of low-dose , step-up stimulation with recombinant FSH were started . In both groups , approximately 30 % of cycles still remained anovulatory . In the down-regulated subgroup , this mainly happened in the first cycle . In each group , ovulation was achieved in 14 cycles , intrauterine insemination was performed , and five pregnancies were obtained . This result ed in a pregnancy rate of 36 % per ovulatory cycle in both groups . Overall , 50 % of the formerly unreactive patients in both groups overcame childlessness . In achieving this , long-term treatment with GnRH analogues was as successful as laparoscopic laser diathermy OBJECTIVE To compare the effectiveness of laparoscopic ovarian diathermy with gonadotropin ovulation induction for women with clomiphene citrate-resistant polycystic ovary syndrome . DESIGN R and omized controlled trial . SETTING A tertiary referral fertility clinic . PATIENT(S ) Women with anovulatory infertility secondary to clomiphene-resistant polycystic ovary syndrome . Inclusion criteria were age of < 39 years , body mass index of < 35 kg/ Output:	Our result revealed that there was no evidence of a significant difference in rates of clinical pregnancy and miscarriage in women with clomiphene citrate-resistant PCOS undergoing LOD compared to the gonadotropin arm . The decrease in multiple pregnancies rate in women undergoing LOD makes this option attractive . The increase in live birth rate in the gonadotropin group may be because of the higher rate of multiple pregnancies in these women .
MS21823	*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 Symptomatic oral lichen planus ( OLP ) has been palliated with a wide spectrum of topical and systemic therapies . Although the majority of management strategies include corticosteroids , few have been evaluated in r and omized controlled trials . OBJECTIVE We investigated the acceptability and efficacy of topical fluticasone propionate spray ( FP ) and betamethasone sodium phosphate mouthrinse ( BSP ) upon the signs and symptoms of OLP , assessing patient quality of life changes as a consequence of these therapies . METHODS We implemented a r and omized , crossover study in which each drug was administered for a period of 6 weeks with an intervening washout period of 2 weeks at an outpatient oral medicine unit in London , United Kingdom . We treated 48 patients with biopsy-proven symptomatic OLP , and 44 patients ( 92 % ) completed the study . The dosage was 50 microg two dose unit sprays and BSP 500 microg , each 4 times daily . Symptomatic improvement was evaluated by means of a visual analogue scale ( VAS ) , the McGill pain score , the Oral Health Impact Profile ( OHIP ) , and Oral Health Quality of Life ( OHQoL ) question naires . The total surface area of the lesions , including all white , erythematous , and ulcerative lesions was measured at each visit . The efficacy , ease of application , and adverse effects associated with each medication were recorded . RESULTS Both FP and BSP mouthwash caused both a statistically significant reduction in painful symptoms as measured by the VAS and improvement in quality of life as measured by the OHIP and OHoQL indices . There was no significant difference between the two corticosteroids in their efficacy in reducing painful symptoms ( measured by the VAS ) or in their effect on patient quality of life . Both FP and BSP significantly reduced the surface area of oral lesions . However , FP was statistically significantly better than BSP in reducing lesion surface area . There was no statistically significant difference between the patient-assessed effects of the 2 therapies . CONCLUSIONS FP and BSP are both effective in the short-term clinical management of symptomatic OLP . FP is more acceptable to patients than BSP because of the convenience of the spray form OBJECTIVE Our purpose was to investigate the efficacy and safety of 0.1 % topical tacrolimus in erosive or ulcerative oral lichen planus . METHODS This was an open-label , noncomparative study conducted in an outpatient oral medicine unit in London , United Kingdom . The study covered an 8-week period with a 22-week follow-up after cessation of therapy . Nineteen patients , aged 28 to 87 years with biopsy-proven oral lichen planus refractory to , or dependent on , systemic immunosuppressive agents , were enrolled . Seventeen patients ( 89 % ) completed the study . Application of 0.1 % tacrolimus was administered to all symptomatic oral mucosal lesions . Clinical review took place 1 , 3 , 5 , 7 , and 8 weeks after commencing therapy . Alleviation of symptoms was evaluated by using a visual analogue scale as well as the McGill Pain and Oral Health Impact profile question naires . The extent of the oral mucosal erosion or ulceration was directly measured by the same clinician at all visits . Safety assessment s included monitoring of adverse events , complete blood cell count , renal and hepatic clinical chemistry , and tacrolimus blood concentrations . RESULTS Tacrolimus caused a statistically significant improvement in symptoms within 1 week of commencement of therapy . A mean decrease of 73.3 % occurred in the area of ulceration over the 8-week study period . Local irritation ( in 6 subjects , 35 % ) was the most commonly reported adverse effect . Laboratory values showed no significant changes with time . Therapeutic levels of tacrolimus were demonstrated in 8 subjects but were unrelated to the extent of oral mucosal involvement . Thirteen of 17 patients suffered a relapse of oral lichen planus within 2 to 15 weeks of cessation of tacrolimus therapy . CONCLUSION Topical tacrolimus is effective therapy for erosive or ulcerative oral lichen planus Background Economic evaluations to inform decisions about allocation of health re sources are scarce in Low and Middle Income Countries , including in Sri Lanka . This is in part due to a lack of country-specific utility weights , which are necessary to derive appropriate Quality Adjusted Life Years . The EQ-5D-3L , a generic multi-attribute instrument ( MAUI ) , is most widely used to measure and value health states in high income countries ; nevertheless , the sensitivity of generic MAUIs has been criticised in some conditions such as cancer . This article describes a protocol to produce both a generic EQ-5D-3L and cancer specific EORTC-8D utility index in Sri Lanka . Method EQ-5D-3L and EORTC-8D health states will be valued using the Time Trade-Off technique , by a representative population sample ( n = 780 invited ) identified using stratified multi-stage cluster sampling with probability proportionate to size method . Households will be r and omly selected within 30 clusters across four districts ; one adult ( ≥18 years ) within each household will be selected using the Kish grid method . Data will be collected via face-to-face interview , with a Time Trade-Off board employed as a visual aid . Of the 243 EQ-5D-3L and 81,290 EORTC-8D health states , 196 and 84 respectively will be directly valued . In EQ-5D-3L , all health states that combine level 3 on mobility with either level 1 on usual activities or self-care were excluded . Each participant will first complete the EQ-5D-3L , rank and value 14 EQ-5D-3L states ( plus the worst health state and “ immediate death ” ) , and then rank and value seven EORTC-8D states ( plus “ immediate death ” ) . Participant demographic and health characteristics will be also collected . Regression models will be fitted to estimate utility indices for EQ-5D-3L and EORTC-8D health states for Sri Lanka . The dependent variable will be the utility value . Different specifications of independent variables will be derived from the ordinal EQ-5D-3L to test for the best-fitting model . Discussion In Sri Lanka , a LMIC health state valuation will have to be carried out using face to face interview instead of online methods . The proposed study will provide the first country-specific health state valuations for Sri Lanka , and one of the first valuations to be completed in a South Asian Country UNLABELLED Implant overdentures and conventional prostheses have been compared in several trials using a variety of functional and oral health-related quality of life ( OHQOL ) outcomes . In this paper , we describe the impact of implant overdentures on general and OHQOL in seniors . OBJECTIVES To compare the oral health-related and general quality of life of seniors ( aged 65 - 75 years ) who received either m and ibular implant overdentures or conventional dentures . METHODS Sixty edentulous patients were recruited . Thirty received m and ibular overdentures retained by two implants ( IOD ) and a conventional maxillary denture , the other 30 subjects received new maxillary and m and ibular conventional complete dentures ( CD ) . All completed the 20-item version of the Oral Health Impact Profile ( OHIP-20 ) before treatment , then at two and 6 months after delivery of the dentures . The SF-36 general health question naire was completed at baseline and 6 months only . RESULTS Pretreatment and 6-month data from 55 subjects were analyzed . Those who received the IODs had significantly better OHIP-20 total scores at 6 months . Results for IOD subjects were also superior in the functional limitation , physical pain , physical disability and psychological disability subscales . While no significant between group difference was found on the SF-36 health survey , significant pre-post-treatment differences within the IOD group were detected for the role emotional , vitality and the social function scales . CONCLUSIONS M and ibular overdentures retained by two implants provide elderly patients with better OHQOL . General health-related quality of life improved in the implant group BACKGROUND Lichen planus is a common chronic inflammatory mucocutaneous disease , affecting 0.1 % to 4 % of the general population . There is no published r and omized active control clinical trial on pimecrolimus for the treatment of oral lichen planus ( OLP ) . OBJECTIVE The purpose of this study was to compare the efficacy and safety of pimecrolimus 1 % cream with triamcinolone acetonide 0.1 % paste in treating OLP . METHODS In this investigator-blinded parallel-group r and omized clinical trial , 40 patients were r and omly assigned in two equal groups to receive either pimecrolimus 1 % cream or triamcinolone acetonide 0.1 % paste 4 times daily for a total of 2 months and followed up for another 2 months . The patients were assessed for painful symptoms measured by visual analog scale , the Oral Health Impact Profile score , and objective clinical score . Nonparametric tests were used to assess the main outcomes . Intention-to-treat analysis was used . RESULTS Eighteen patients in pimecrolimus group and 17 patients in triamcinolone group finished the 4-month trial course . Both pimecrolimus and triamcinolone groups showed significant improvement in all measured efficacy end points throughout the visits . There was no significant difference between changes from baseline median values of pimecrolimus and triamcinolone groups after treatment termination in terms of visual analog scale score ( -9.8 + /- 11.3 vs -8.4 + /- 18.3 , P = .70 ) , Oral Health Impact Profile score ( -1.5 + /- 2.6 vs -1.6 + /- 2.1 , P = .38 ) , and clinical score ( -0.7 + /- 0.6 vs -0.8 + /- 0.7 , P = .86 ) , respectively . Two patients in pimecrolimus group experienced prominent but transient burning sensation whereas none of the patients in triamcinolone group had any prominent adverse event ( P = .24 ) . LIMITATIONS Blood levels in pimecrolimus group were not measured and carcinogenicity of pimecrolimus , especially in its long-term use for OLP , is yet to be determined . CONCLUSION This study showed that patients with OLP may benefit from both topical pimecrolimus and triamcinolone acetonide therapy with minimal side effects . Further studies should be conducted to assess the maintenance effects and long-term safety of both drugs ( Cochrane skin group identifier : CSG TrialNo . 22 ) Background : Dermatologists see patients with oral mucosal conditions . Objectives : To evaluate oral health-related quality of life ( OHRQoL ) and the burden of disease of dermatological patients with oral mucosal diseases . Methods : All consecutive patients ( April 2005 to November 2006 ) coming to the oral health care unit of the IDI-IRCCS in Rome were asked to complete oral health-specific ( 14-item Oral Health Impact Profile , OHIP-14 ) , generic health status ( 12-item Short Form of Medical Outcome Study , SF-12 ) and general psychological ( 12-item General Health Question naire , GHQ-12 ) question naires . Physicians and patients gave a global assessment of severity of disease on a 5-point scale . Results : 206 patients participated . Recurrent aphthous stomatitis ( RAS ) had the highest impact on OHRQoL. Women had poorer OHRQoL both on physical and mental scales of the SF-12 . 33.7 % of patients were GHQ-positive with women showing a much higher prevalence than men ( 39.7 vs. 20.3 % ) . OHIP-14 high scores were observed in RAS , followed by oral lichen planus and burning mouth syndrome . Patients whose condition was ‘ underestimated ’ by the physicians had the worst OHRQoL and psychological status . Conclusions : Administration of specific and generic question naires provides a detailed picture of the impact of oral diseases on patients , which adds information that may be useful in clinical practice . The possible contribution of such tools should be assessed in a r and omized controlled trial The aim of this study was to describe prospect ively quality of life and mood in patients with oral or oropharyngeal cancer treated with surgery + /- radiotherapy . Seventy-five patients completed the EORTC Core Question naire , the EORTC Head and Neck Cancer module and the Center for Epidemiologic Studies ' Depression Scale before treatment and 6 and 12 months later . There was a significant deterioration of physical functioning , fatigue and almost all head and neck symptoms except pain , which improved . Patients with stage III/IV and patients receiving combined treatment had significantly worse physical symptoms compared to patients with stage I/II and patients treated with surgery only , respectively . Before and after treatment there was a high level of depressive symptomatology . However , after treatment a gradual improvement in emotional functioning occurred . Surgical treatment for oral or oropharyngeal cancer results in significant deterioration of physical functioning and symptoms during the first year , especially when combined with radiotherapy . Despite this , there is an improvement of emotional functioning after treatment , probably as a result of adaptation and coping processes OBJECTIVE To test the reliability and responsiveness of the Chronic Oral Mucosal Diseases Question naire ( COMDQ ) , in measuring the quality of life ( QofL ) in patients with chronic oral mucosal conditions . METHODS A r and om sample of 160 patients with the following chronic oral mucosal conditions , recurrent aphthous stomatitis , Output:	The findings differ but , overall , do not provide evidence that patients with OPMDs have a poorer QoL compared with healthy patients .
MS21824	*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 The aim of this prospect i ve clinical study was to assess the risk factors associated with failure of mini-implants used for orthodontic anchorage . MATERIAL S AND METHODS A total of 140 mini-implants in 44 patients , including 48 miniplates and 92 freest and ing miniscrews , were examined in the study . A variety of orthodontic loads were applied . The majority of implants were placed in the posterior maxilla ( 104/140 ) , and the next most common location was the posterior m and ible ( 34/140 ) . RESULTS A cumulative survival rate of 89 % ( 125/140 ) was found by Kaplan-Meier analysis . There was no significant difference in the survival rate between miniplates and freest and ing miniscrews , but miniplates were used in more hazardous situations . The Cox proportional-hazards regression model identified anatomic location and peri-implant soft tissue character as 2 independent prognostic indicators . The estimated relative risk of implant failure in the posterior m and ible was 1.101 ( 95 % confidence interval , 0.942 to 1.301 ; P = .046 ) . The risk ratio of failure for implants surrounded by nonkeratinized mucosa was 1.117 ( 95 % confidence interval , 0.899 to 1.405 ; P = .026 ) . DISCUSSION AND CONCLUSION The results confirmed the effectiveness of orthodontic mini-implants , but in certain situations adjustment of the treatment plan or modifications in the technique of implant placement may lead to improved success rates INTRODUCTION The purpose of this study was to determine the success rate , positional stability , and patient evaluation of orthodontic mini-implants ( OMIs ) . METHODS Thirteen patients ( 8 girls , 5 boys ; average age , 14 years 10 months ) were treated with 82 OMIs measuring 1.6 mm in diameter and 6 mm in length placed in the buccal alveoli ( 1 unloaded OMI and 1 loaded OMI per quadrant ) . The right or left side of each arch was r and omly selected for immediate loading with up to 250 g of direct force ; the contralateral side was loaded 3 to 5 weeks later . Serial impressions , clinical observations , and orthodontic maintenance were performed until adequate space closure was achieved . RESULTS The overall OMI success rate was 70.73 % . As calculated with a mixed-model analysis , there was no statistically significant difference between the success rates of immediately loaded OMIs ( 80.0 % ) and delayed loaded OMIs ( 80.95 % ) . The combined success rate for loaded OMIs ( 80.49 % ) was significantly higher than that of unloaded OMIs ( 60.98 % ) . Patients ' motivation for OMI treatment was primarily the desire to avoid headgear . Using a 100-mm visual analog scale , the patients indicated average scores of 54.77 for the amount of pain during OMI placement and 27.10 for the amount of pain during OMI removal . CONCLUSIONS OMIs are a predictable , effective , and well-tolerated anchorage source for adolescents . Neither the timing of force application nor the force itself precipitated failure of the OMIs . Orthodontic forces can be applied immediately to OMIs . Various anatomic and behavioral conditions unique to adolescents and a clinical learning curve can affect the success rate of OMIs AIM The purpose of this investigation was to determine and compare the accuracy of four available mechanical torque-limiting gauges ( MTLGs ) for mini-screw placement . MATERIAL S AND METHODS The torque outputs of six r and omly obtained MTLGs , either of the screwdriver or torque ratchet type of four mini-screw manufacturers were obtained . Mounted on a joint , a universal testing machine applied perpendicular force to a lever arm with a crosshead speed of 1 mm/min . For each device , 10 repetitions of the corresponding target torque level were recorded after initial sterilisation ( 1 ) and after 5 , 10 , 20 , 50 and 100 times to evaluate its potential influence on MTLGs . The breakpoints ( N cm ) were calculated for comparison of the groups . Descriptive statistics and mean breakpoints values for each MTLG computed and compared with the reference values indicated on the respective torque gauges provided by the producer . RESULTS The mean torque values for the AbsoAnchor MTLG devices were significantly below torque levels , but provide consistent torque values . All but one obtained values for the Spider Screw , MTLG of the screw driver type , were within the indicated moment range during the first 50-times of sterilization process . But after 100-times of steam sterilization all mean breakpoint values were relevantly higher than the indicated torque range values . Each individual MTLG produced independently constant breakpoint torque values , but differed significantly from each other . For all but the Spider Screw MTLG , the sterilisation process had a statistically significant different influence at the various breakpoint torque levels . CONCLUSION After application of the manufacturers ' preset torque levels , significant variations were observed between individual devices . The torque output of each individual device deviated in varying degrees from target torque values and was influenced by various degrees by the sterilisation process over time Output:	There is a positive association between MI primary stability and CtTh of the receptor site .
MS21825	*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 purpose of this study was to examine the effect of isokinetic eccentric ( ECC ) and concentric ( CON ) training at two velocities [ fast , 180 ° s−1 ( 3.14 rad s−1 ) and slow,30 ° s−1(0.52 rad s−1 ) ] on muscle hypertrophy . Twenty-four untrained volunteers ( age 18–36 years ) participated in fast- ( n=13 ) or slow- ( n=11 ) velocity training , where they trained one arm eccentrically for 8 weeks followed by CON training of the opposite arm for 8 weeks . Ten subjects served as controls ( CNT ) . Subjects were tested before and after training for elbow flexor muscle thickness by sonography and isokinetic strength ( Biodex ) . Overall , ECC training result ed in greater hypertrophy than CON training ( P<0.01 ) . No significant strength or hypertrophy changes occurred in the CNT group . ECC ( 180 ° s−1 ) training result ed in greater hypertrophy than CON ( 180 ° s−1 ) training and CON ( 30 ° s−1 ) training ( P<0.01 ) . ECC ( 30 ° s−1 ) training result ed in greater hypertrophy than CON ( 180 ° s−1 ) training ( P<0.05 ) , but not CON ( 30 ° s−1 ) training . ECC ( 180 ° s−1 ) training result ed in the greatest increases in strength ( P<0.01 ) . We conclude that ECC fast training is the most effective for muscle hypertrophy and strength gain We have reported that the acute postexercise increases in muscle protein synthesis rates , with differing nutritional support , are predictive of longer-term training-induced muscle hypertrophy . Here , we aim ed to test whether the same was true with acute exercise-mediated changes in muscle protein synthesis . Eighteen men ( 21 ± 1 yr , 22.6 ± 2.1 kg/m(2 ) ; means ± SE ) had their legs r and omly assigned to two of three training conditions that differed in contraction intensity [ % of maximal strength ( 1 repetition maximum ) ] or contraction volume ( 1 or 3 sets of repetitions ) : 30%-3 , 80%-1 , and 80%-3 . Subjects trained each leg with their assigned regime for a period of 10 wk , 3 times/wk . We made pre- and posttraining measures of strength , muscle volume by magnetic resonance ( MR ) scans , as well as pre- and posttraining biopsies of the vastus lateralis , and a single postexercise ( 1 h ) biopsy following the first bout of exercise , to measure signaling proteins . Training-induced increases in MR-measured muscle volume were significant ( P < 0.01 ) , with no difference between groups : 30%-3 = 6.8 ± 1.8 % , 80%-1 = 3.2 ± 0.8 % , and 80%-3= 7.2 ± 1.9 % , P = 0.18 . Isotonic maximal strength gains were not different between 80%-1 and 80%-3 , but were greater than 30%-3 ( P = 0.04 ) , whereas training-induced isometric strength gains were significant but not different between conditions ( P = 0.92 ) . Biopsies taken 1 h following the initial resistance exercise bout showed increased phosphorylation ( P < 0.05 ) of p70S6 K only in the 80%-1 and 80%-3 conditions . There was no correlation between phosphorylation of any signaling protein and hypertrophy . In accordance with our previous acute measurements of muscle protein synthetic rates a lower load lifted to failure result ed in similar hypertrophy as a heavy load lifted to failure Ten healthy young men ( 21.0 + /- 1.5 yr , 1.79 + /- 0.1 m , 82.7 + /- 14.7 kg , means + /- SD ) participated in 8 wk of intense unilateral resistance training ( knee extension exercise ) such that one leg was trained ( T ) and the other acted as an untrained ( UT ) control . After the 8 wk of unilateral training , infusions of L-[ring-d(5)]phenylalanine , L-[ring-(13)C(6)]phenylalanine , and d(3)-alpha-ketoisocaproic acid were used to measure mixed muscle protein synthesis in the T and UT legs by the direct incorporation method [ fractional synthetic rate ( FSR ) ] . Protein synthesis was determined at rest as well as 4 h and 28 h after an acute bout of resistance exercise performed at the same intensity relative to the gain in single repetition maximum before and after training . Training increased mean muscle fiber cross-sectional area only in the T leg ( type I : 16 + /- 10 % ; type II : 20 + /- 19 % , P < 0.05 ) . Acute resistance exercise increased muscle protein FSR in both legs at 4 h ( T : 162 + /- 76 % ; UT : 108 + /- 62 % , P < 0.01 vs. rest ) with the increase in the T leg being significantly higher than in the UT leg at this time ( P < 0.01 ) . At 28 h postexercise , FSR in the T leg had returned to resting levels ; however , the rate of protein synthesis in the UT leg remained elevated above resting ( 70 + /- 49 % , P < 0.01 ) . We conclude that resistance training attenuates the protein synthetic response to acute resistance exercise , despite higher initial increases in FSR , by shortening the duration for which protein synthesis is elevated The authors investigated the effects of low-intensity resistance training on muscle size and strength in older men and women . Thirty-five participants ( age 59 - 76 yr ) were r and omly assigned to 2 groups and performed low-intensity ( 50 % of 1-repetition maximum ) knee-extension and -flexion exercises with either slow movement and tonic force generation ( LST ; 3-s eccentric , 3-s concentric , and 1-s isometric actions with no rest between repetitions ) or normal speed ( LN ; 1-s concentric and 1-s eccentric actions with 1-s rests between repetitions ) twice a week for 12 wk ( 2-wk preparation and 10-wk intervention ) . The LST significantly increased thigh-muscle thickness , as well as isometric knee-extension and -flexion strength . The LN significantly improved strength , but its hypertrophic effect was limited . These results indicate that even for older individuals , the LST can be an effective method for gaining muscle mass and strength Dual-energy X-ray absorptiometry ( DEXA ) is reported to be inferior to computed tomography ( CT ) to measure changes in appendicular soft tissue composition . We compared CT- and DEXA-measured thigh muscle and fat mass to evaluate the r and om and systematic discrepancies between these two methods . Thigh skeletal muscle area ( single-slice CT ) was suboptimally ( r(2 ) = 0.74 , P < 0.0001 ) related to DEXA-measured thigh fat-free mass ( FFM ) . In contrast , thigh muscle and adipose tissue volumes ( multislice CT ) were highly related to DEXA-measured thigh FFM and fat ( both r(2 ) = 0.96 , P < 0.0001 ) . DEXA-measured leg fat was significantly less than multislice-CT-measured leg adipose tissue volume , whereas multislice-CT-measured leg muscle mass was less ( P < 0.0001 ) than DEXA-measured leg FFM . The systematic discrepancies between the two approaches were consistent with the 10 - 15 % nonfat components of adipose tissue . In conclusion , CT and DEXA measures of appendicular soft tissue are highly related . Systematic differences between DEXA and CT likely relate to the underlying principles of the techniques A two-arm , prospect i ve , r and omized , controlled trial study was conducted to investigate the effects of movement velocity during progressive resistance training ( PRT ) on the size and contractile properties of individual fibers from human vastus lateralis muscles . The effects of age and sex were examined by a design that included 63 subjects organized into four groups : young ( 20 - 30 yr ) men and women , and older ( 65 - 80 yr ) men and women . In each group , one-half of the subjects underwent a traditional PRT protocol that involved shortening contractions at low velocities against high loads , while the other half performed a modified PRT protocol that involved contractions at 3.5 times higher velocity against reduced loads . Muscles were sample d by needle biopsy before and after the 14-wk PRT program , and functional tests were performed on permeabilized individual fiber segments isolated from the biopsies . We tested the hypothesis that , compared with low-velocity PRT , high-velocity PRT results in a greater increase in the cross-sectional area , force , and power of type 2 fibers . Both types of PRT increased the cross-sectional area , force , and power of type 2 fibers by 8 - 12 % , independent of the sex or age of the subject . Contrary to our hypothesis , the velocity at which the PRT was performed did not affect the fiber-level outcomes substantially . We conclude that , compared with low-velocity PRT , resistance training performed at velocities up to 3.5 times higher against reduced loads is equally effective for eliciting an adaptive response in type 2 fibers from human skeletal muscle PURPOSE To compare effects on strength in the early phase of resistance training with one or three sets and fast or slow speeds . METHODS A total of 115 healthy , untrained subjects were r and omized to a control group or one of four training groups : one set fast ( approximately 140 degrees.s(-1 ) ) , three sets fast , one set slow ( approximately 50 degrees.s(-1 ) ) , or three sets slow . All subjects attended training 3 x wk(-1 ) for 6 wk . Subjects in the training groups performed unilateral elbow flexion contractions with a target six- to eight-repetition maximum load . Control subjects sat at the training bench but did not train . One repetition maximum strength , arm circumference , and biceps skinfold thickness were measured before and after training . RESULTS One slow set increased strength by 25 % ( 95 % CI 13 - 36 % , P < 0.001 ) . Three sets of training produced greater increases in strength than one set ( difference = 23 % of initial strength , 95 % CI 12 - 34 % , P < 0.001 ) and fast training result ed in a greater increase in strength than slow training ( difference = 11 % , 95 % CI 0.2 - 23 % , P = 0.046 ) . The interaction between sets and speed was negative ( -15 % ) and of borderline significance ( P = 0.052 ) , suggesting there is a benefit of training with three sets or fast speeds , but there is not an additive benefit of training with both . CONCLUSIONS Three sets of exercise produce twice the strength increase of one set in the early phase of resistance training . Training fast produces greater strength increases than training slow ; however , there does not appear to be any additional benefit of training with both three sets and fast contractions We previously reported that low‐intensity [ 50 % of one repetition maximum ( 1RM ) ] resistance training with slow movement and tonic force generation ( LST ) causes muscle hypertrophy and strength gain in older participants . The aim of this study was to determine whether resistance training with slow movement and much more reduced intensity ( 30%1RM ) increases muscle size and strength in older adults . Eighteen participants ( 60–77 years ) were r and omly assigned to two groups . One group performed very low‐intensity ( 30 % 1RM ) knee extension exercise with continuous muscle contraction ( LST : 3‐s eccentric , 3‐s concentric , and 1‐s isometric actions with no rest between each repetition ) twice a week for 12 weeks . The other group underwent intermitted muscle contraction ( CON : 1‐s concentric and 1‐s eccentric actions with 1‐s rest between each repetition ) for the same time period . The 1RM , isometric and isokinetic strengths , and cross‐sectional image of the mid‐thigh obtained by magnetic resonance imaging were examined before and after the intervention . LST significantly increased the cross‐sectional area of the quadriceps muscle ( 5·0 % , P<0·001 ) and isometric and isokinetic knee extension strengths ( P<0·05 ) . CON failed to increase muscle size ( 1·1 % , P = 0·12 ) , but significantly improved its strength ( P<0·05 ) . These results indicate that even if the intensity is as low as 30 % 1RM , LST can increase muscle size and strength in healthy older adults . The large total contraction time may be related to muscle hypertrophy and strength gain . LST would be useful for preventing sarcopenia in older individuals The purpose of this study was to investigate the effects of a six-week ( 16 - 17 training sessions ) low velocity resistance training program ( LV ) on various performance measures as compared to a traditional strength ( TS ) and a traditional muscular endurance ( TE ) resistance training program . Thirty-four healthy adult females ( 21.1 ± 2.7 y ) were r and omly divided into 4 groups : control ( C ) , TS , TE , and LV . Workouts consisted of 3 exercises : leg press ( LP ) , back squat ( SQ ) , and knee extension ( KE ) . Each subject was pre- and posttested for 1 repetition maximum ( 1RM ) , muscular endurance , maximal oxygen consumption ( VO2max ) , Output:	Results Results indicate that hypertrophic outcomes are similar when training with repetition duration s ranging from 0.5 to 8 s. Conclusions From a practical st and point it would seem that a fairly wide range of repetition duration s can be employed if the primary goal is to maximize muscle growth .
MS21826	*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 negative affect is a common precipitant of alcohol relapse , there are few interventions for alcohol dependence that specifically target negative affect . In this stage 1a/1b treatment development study , several affect regulation strategies ( e.g. , mindfulness , prolonged exposure , distress tolerance ) were combined to create a new treatment supplement called affect regulation training ( ART ) , which could be added to enhance cognitive-behavioral therapy ( CBT ) for alcohol dependence . A draft therapy manual was given to therapists and treatment experts before being administered to several patients who also provided input . After two rounds of manual development ( stage 1a ) , a pilot r and omized clinical trial ( N=77 ) of alcohol-dependent out patients who reported drinking often in negative affect situations was conducted ( stage 1b ) . Participants received 12-weekly , 90-minute sessions of either CBT for alcohol dependence plus ART ( CBT+ART ) or CBT plus a healthy lifestyles control condition ( CBT+HLS ) . Baseline , end-of-treatment , and 3- and 6-month posttreatment interviews were conducted . For both treatment conditions , participant ratings of treatment satisfaction were high , with CBT+ART rated significantly higher . Drinking outcome results indicated greater reductions in alcohol use for CBT+ART when compared to CBT+HLS , with moderate effect sizes for percent days abstinent , drinks per day , drinks per drinking day , and percent heavy drinking days . Overall , findings support further research on affect regulation interventions for negative affect drinkers AIMS Acamprosate in combination with psychosocial treatment has been shown to be effective for the treatment of alcohol dependence . The goal of the present study was to determine whether the addition of psychosocial intervention to the medical prescription of acamprosate contributes to treatment outcome . METHODS Patients ( n = 248 ) meeting DSM-IV criteria for alcohol dependence or abuse were recruited in 14 outpatient treatment centres and r and omized into one of three treatment conditions : acamprosate ; acamprosate plus minimal intervention aim ed at motivational enhancement ( 3-weekly sessions of 20 min ) ; and acamprosate plus brief cognitive behavioural therapy ( 7-weekly sessions of 60 min ) . Acamprosate was prescribed for 28 weeks , medically monitored by a physician on six occasions lasting 10 min . Drinking behaviour , medication compliance and psychological distress were assessed throughout the treatment period . Follow-up assessment was undertaken 6 months after termination of pharmacological treatment . RESULTS Of 241 patients with intention to treat ( ITT ) , 114 ( 47.3 % ) remained in treatment for the full 28 weeks ; 169 of the ITT population ( 70.1 % ) were seen for follow-up . No statistically significant differences were found between treatment groups for any of the drinking outcomes either at the end of the 28 weeks of treatment or at 6-month follow-up . There were no statistically significant differences in medication compliance , drop-out rates , or psychological distress . However , a significant interaction effect was observed between treatment centre and treatment group , indicating that brief interventions were differentially effective in different treatment centres . CONCLUSIONS A clear supplemental value of minimal and brief psychosocial interventions to the prescription of acamprosate was not demonstrated . The widely held belief that pharmacotherapy for alcohol dependence should always be combined with psychosocial intervention is debatable and merits further research BACKGROUND This study evaluated the serotonergic antidepressant nefazodone versus placebo and specific cognitive-behavioral therapy ( CBT ) versus nondirective group counseling ( GC ) for relapse prevention in alcohol dependence in a large prospect i ve , r and omized , and placebo-controlled double-blind study at 3 German university centers . METHOD 242 male patients fulfilling at least 5 criteria for alcohol dependence according to DSM-IV and ICD-10 were eligible , after detoxification , for one of the following treatment combinations : nefazodone + CBT , nefazodone + GC , placebo + CBT , and placebo + GC . Either nefazodone or placebo was administered throughout the evaluation period of 15 months . Either CBT or GC was applied during the first 12 weeks as group therapy according to operationalized manuals . The main outcome measures ( assessed at 3 and 12 months of treatment ) were the cumulative number of abstinent days , the amount of ethanol consumed during specified evaluation periods of 3 and 12 months , the number of relapses , and the duration of time until first relapse . RESULTS After 12 weeks of treatment , no statistically significant differences were observed between the 4 treatment combinations in any outcome measure . After 52 weeks , the only significant difference was observed in the amount of ethanol consumed , with the nefazodone + GC group showing higher alcohol intake than the other 3 groups . CONCLUSIONS The results from this carefully design ed clinical trial suggest that the 4 treatment combinations do not differ substantially in their efficacy for relapse prevention in nondepressed , severely alcohol-dependent patients . Nefazodone might even increase the risk of consuming a larger amount of ethanol per relapse in a subset of patients . CBT as performed in this study was associated with little additional benefit compared with structured GC Summary The comparative effects of alcoholism treatment programmes were examined by r and omly assigning 113 male and female detoxified alcoholics to either : a 6-week inpatient programme , a 6-week outpatient programme or a single confrontational interview . On a variety of outcome measures , that included both levels of drinking and general functioning taken 6 and 18 months after intake , no treatment appeared to be consistently more effective than another . Furthermore , those who stayed in treatment did not show significantly more long-term improvement than those who refused or dropped out of treatment . Abstinent subjects felt more often than drinkers that they had achieved the goals they had set themselves and by the final follow-up there were many positive differences in apparent lifestyle . Although individual drinking patterns were unstable , on average , almost half the subjects located had either abstained or were drinking moderately . Patient and treatment variables combined explained up to 57 % of the variance in amount drunk after treatment , with patient variables providing the strongest associations OBJECTIVE This study was design ed to conduct a r and omized controlled trial of motivational enhancement therapy ( MET ) with two control conditions : nondirective reflective listening ( NDRL ) and no further counseling ( NFC ) ; and to conduct this study in a sample of patients with a primary diagnosis of mild to moderate alcohol dependence , in a " real-life " clinical setting . METHOD Patients with mild to moderate alcohol dependence were recruited , assessed and treated at the Community Alcohol and Drug Service of Christchurch , New Zeal and . All patients received a feedback/education session before r and omization to either four sessions of MET , four sessions of NDRL , or NFC . Outcome data on 122 subjects ( 57.4 % men ) were obtained 6 months following the end of treatment , by an interviewer who was blind to the treatment condition . The primary drinking outcome was unequivocal heavy drinking , defined as drinking 10 or more st and ard drinks six or more times in the follow-up period . Global assessment scale ( GAS ) measured general personal/social functioning . RESULTS Of patients treated with MET , 42.9 % showed unequivocal heavy drinking compared with 62.5 % of the NDRL and 65.0 % of the NFC groups ( p = .04 ) . No significant differences were found for GAS score according to treatment condition . CONCLUSIONS In patients with mild to moderate alcohol dependence , MET is more effective for reducing unequivocal heavy drinking than either a feedback/education session alone or four sessions of NDRL . MET can be considered an effective " value added " counseling intervention in a real-life clinical setting . In patients with mild to moderate alcohol dependence , nondirective reflective listening provides no additional advantage over a feedback/education session alone CONTEXT Alcohol dependence treatment may include medications , behavioral therapies , or both . It is unknown how combining these treatments may impact their effectiveness , especially in the context of primary care and other nonspecialty setting s. OBJECTIVES To evaluate the efficacy of medication , behavioral therapies , and their combinations for treatment of alcohol dependence and to evaluate placebo effect on overall outcome . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial conducted January 2001-January 2004 among 1383 recently alcohol-abstinent volunteers ( median age , 44 years ) from 11 US academic sites with Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , diagnoses of primary alcohol dependence . INTERVENTIONS Eight groups of patients received medical management with 16 weeks of naltrexone ( 100 mg/d ) or acamprosate ( 3 g/d ) , both , and /or both placebos , with or without a combined behavioral intervention ( CBI ) . A ninth group received CBI only ( no pills ) . Patients were also evaluated for up to 1 year after treatment . MAIN OUTCOME MEASURES Percent days abstinent from alcohol and time to first heavy drinking day . RESULTS All groups showed substantial reduction in drinking . During treatment , patients receiving naltrexone plus medical management ( n = 302 ) , CBI plus medical management and placebos ( n = 305 ) , or both naltrexone and CBI plus medical management ( n = 309 ) had higher percent days abstinent ( 80.6 , 79.2 , and 77.1 , respectively ) than the 75.1 in those receiving placebos and medical management only ( n = 305 ) , a significant naltrexone x behavioral intervention interaction ( P = .009 ) . Naltrexone also reduced risk of a heavy drinking day ( hazard ratio , 0.72 ; 97.5 % CI , 0.53 - 0.98 ; P = .02 ) over time , most evident in those receiving medical management but not CBI . Acamprosate showed no significant effect on drinking vs placebo , either by itself or with any combination of naltrexone , CBI , or both . During treatment , those receiving CBI without pills or medical management ( n = 157 ) had lower percent days abstinent ( 66.6 ) than those receiving placebo plus medical management alone ( n = 153 ) or placebo plus medical management and CBI ( n = 156 ) ( 73.8 and 79.8 , respectively ; P<.001 ) . One year after treatment , these between-group effects were similar but no longer significant . CONCLUSIONS Patients receiving medical management with naltrexone , CBI , or both fared better on drinking outcomes , whereas acamprosate showed no evidence of efficacy , with or without CBI . No combination produced better efficacy than naltrexone or CBI alone in the presence of medical management . Placebo pills and meeting with a health care professional had a positive effect above that of CBI during treatment . Naltrexone with medical management could be delivered in health care setting s , thus serving alcohol-dependent patients who might otherwise not receive treatment . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00006206 OBJECTIVE To assess the benefits of matching alcohol dependent clients to three different treatments with reference to a variety of client attributes . METHODS Two parallel but independent r and omized clinical trials were conducted , one with alcohol dependent clients receiving outpatient therapy ( N = 952 ; 72 % male ) and one with clients receiving aftercare therapy following inpatient or day hospital treatment ( N = 774 ; 80 % male ) . Clients were r and omly assigned to one of three 12-week , manual-guided , individually delivered treatments : Cognitive Behavioral Coping Skills Therapy , Motivational Enhancement Therapy or Twelve-Step Facilitation Therapy . Clients were then monitored over a 1-year posttreatment period . Individual differences in response to treatment were modeled as a latent growth process and evaluated for 10 primary matching variables and 16 contrasts specified a priori . The primary outcome measures were percent days abstinent and drinks per drinking day during the 1-year posttreatment period . RESULTS Clients attended on average two-thirds of treatment sessions offered , indicating that substantial amounts of treatment were delivered , and research follow-up rates exceeded 90 % of living subjects interviewed at the 1-year posttreatment assessment . Significant and sustained improvements in drinking outcomes were achieved from baseline to 1-year posttreatment by the clients assigned to each of these well-defined and individually delivered psychosocial treatments . There was little difference in outcomes by type of treatment . Only one attribute , psychiatric severity , demonstrated a significant attribute by treatment interaction : In the outpatient study , clients low in psychiatric severity had more abstinent days after 12-step facilitation treatment than after cognitive behavioral therapy . Neither treatment was clearly superior for clients with higher levels of psychiatric severity . Two other attributes showed time-dependent matching effects : motivation among out patients and meaning-seeking among aftercare clients . Client attributes of motivational readiness , network support for drinking , alcohol involvement , gender , psychiatric severity and sociopathy were prognostic of drinking outcomes over time . CONCLUSIONS The findings suggest that psychiatric severity should be considered when assigning clients to outpatient therapies . The lack of other robust matching effects suggests that , aside from psychiatric severity , providers need not take these client characteristics into account when triaging clients to one or the other of these three individually delivered treatment approaches , despite their different treatment philosophies AIMS To determine the efficacy of motivational enhancement therapy ( MET ) on alcohol use in patients with the hepatitis C virus ( HCV ) and an alcohol use disorder ( AUD ) . DESIGN R and omized , single-blind , controlled trial comparing MET to a control education condition with 6-month Output:	Mean follow-up time : 43 ( 8 - 104 ) weeks with a mean of 6 ( 2 - 18 ) research assessment s. Neither planned weeks , duration of sessions , frequency of sessions per week , nor actual attended sessions were associated with long-term alcohol use outcomes . However , frequency of research assessment s was positively associated with PDA and PHD . CONCLUSION No associations between long-term alcohol use outcomes and planned or actual attended duration of psychosocial treatment in outpatient care . Research assessment s and , accordingly , the research project in itself may influence outcome in studies of psychosocial treatment for alcohol use disorder
MS21827	*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 study the effect of birth centre care on the duration of breast feeding , breast feeding complications , and women 's experiences of breast feeding . DESIGN r and omised controlled trial . SETTING in-hospital birth centre at South Hospital , Stockholm , and st and ard obstetric care in the Greater Stockholm area . SUBJECTS 1230 women with expected date of birth between October 1989 and February 1992 , interested in participating in a birth centre trial , and meeting medical low-risk criteria . 617 women were allocated to the experimental group offered birth centre care ( EG ) , and 613 to the control group offered st and ard obstetric care ( CG ) . MAIN OUTCOME MEASURES duration of breast feeding , breast feeding complications such as sore nipples , engorgement , milk stasis , and mastitis , and women 's experiences of breast feeding . FINDINGS no difference was found between EG and CG in the duration of breast feeding . Ninety-three per cent in both groups were breast feeding exclusively two months post partum . The average number of months of breast feeding , exclusively or partly , when investigated one year after the birth was 8.6 in EG and 8.5 in CG . No difference was observed in women 's experiences of breast feeding , but rather more women in EG than in CG reported sore nipples , 36 % and 30 % respectively ( p = 0.03 ) , and milk stasis , 26 % and 19 % respectively ( p = 0.002 ) . CONCLUSIONS birth centre care had no effect on the duration of breast feeding , or on women 's experiences of breast feeding . Prenatal attitudes were probably more significant predictors of these outcomes than differences in the two modes of maternity care in this population of highly breast feeding-motivated women . The larger proportion of sore nipples and milk stasis in the EG might have been due to earlier discharge , or to midwives less skilled in assisting with breast feeding at the birth centre than in the postpartum wards Objectives To compare the outcome of two methods of maternity care during the antenatal period and at delivery . One was to be midwife‐led for both antenatal care and delivery , the latter taking place in rooms similar to those in one 's own home to simulate home confinement . The other would be consultant‐led with the mothers labouring in the delivery suite rooms with resuscitation equipment for both mother and baby in evidence , monitors present and a delivery bed on which both anaesthetic and obstetric procedures could be easily and safely carried out Abstract Objective : To examine whether intrapartum care and delivery of low risk women in a midwife managed delivery unit differs from that in a consultant led labour ward . Design : Pragmatic r and omised controlled trial . Subjects were r and omised in a 2:1 ratio between the midwives unit and the labour ward . Setting : Aberdeen Maternity Hospital , Grampian . Subjects—2844 low risk women , as defined by existing booking criteria for general practitioner units in Grampian . 1900 women were r and omised to the midwives unit and 944 to the labour ward . Main outcome measures : Maternal and perinatal morbidity . Results : Of the women r and omised to the midwives unit , 647 ( 34 % ) were transferred to the labour ward antepartum , 303 ( 16 % ) were transferred intrapartum , and 80 ( 4 % ) were lost to follow up . 870 women ( 46 % ) were delivered in the midwives unit . Primigravid women ( 255/596 , 43 % ) were significantly more likely to be transferred intrapartum than multigravid women ( 48/577 , 8 % ) . Significant differences between the midwives unit and labour ward were found in monitoring , fetal distress , analgesia , mobility , and use of episiotomy . There were no significant differences in mode of delivery or fetal outcome . Conclusions : Midwife managed intrapartum care for low risk women results in more mobility and less intervention with no increase in neonatal morbidity . However , the high rate of transfer shows that antenatal criteria are unable to determine who will remain at low risk throughout pregnancy and labour Objective To compare perinatal outcomes , maternal outcomes , and interventions in labour by planned place of birth at the start of care in labour for women with low risk pregnancies . Design Prospect i ve cohort study . Setting Engl and : all NHS trusts providing intrapartum care at home , all freest and ing midwifery units , all alongside midwifery units ( midwife led units on a hospital site with an obstetric unit ) , and a stratified r and om sample of obstetric units . Participants 64 538 eligible women with a singleton , term ( ≥37 weeks gestation ) , and “ booked ” pregnancy who gave birth between April 2008 and April 2010 . Planned caesarean sections and caesarean sections before the onset of labour and unplanned home births were excluded . Main outcome measure A composite primary outcome of perinatal mortality and intrapartum related neonatal morbidities ( stillbirth after start of care in labour , early neonatal death , neonatal encephalopathy , meconium aspiration syndrome , brachial plexus injury , fractured humerus , or fractured clavicle ) was used to compare outcomes by planned place of birth at the start of care in labour ( at home , freest and ing midwifery units , alongside midwifery units , and obstetric units ) . Results There were 250 primary outcome events and an overall weighted incidence of 4.3 per 1000 births ( 95 % CI 3.3 to 5.5 ) . Overall , there were no significant differences in the adjusted odds of the primary outcome for any of the non-obstetric unit setting s compared with obstetric units . For nulliparous women , the odds of the primary outcome were higher for planned home births ( adjusted odds ratio 1.75 , 95 % CI 1.07 to 2.86 ) but not for either midwifery unit setting . For multiparous women , there were no significant differences in the incidence of the primary outcome by planned place of birth . Interventions during labour were substantially lower in all non-obstetric unit setting s. Transfers from non-obstetric unit setting s were more frequent for nulliparous women ( 36 % to 45 % ) than for multiparous women ( 9 % to 13 % ) . Conclusions The results support a policy of offering healthy women with low risk pregnancies a choice of birth setting . Women planning birth in a midwifery unit and multiparous women planning birth at home experience fewer interventions than those planning birth in an obstetric unit with no impact on perinatal outcomes . For nulliparous women , planned home births also have fewer interventions but have poorer perinatal outcomes Please cite this paper as : Bernitz S , Roll and R , Blix E , Jacobsen M , Sjøborg K , Øian P. Is the operative delivery rate in low‐risk women dependent on the level of birth care ? A r and omised controlled trial . BJOG 2011;118:1357–1364 This r and omized , controlled trial compared women 's satisfaction with care at an in-hospital birth center with st and ard obstetric care in Stockholm . Subjects were 1230 women with an expected date of birth between October 1989 and February 1992 , who expressed interest in birth center care , and who were medically low risk . The intervention was the r and om allocation of maternity care at the birth center or st and ard obstetric care . Birth center women expressed greater satisfaction with antenatal , intrapartum , and postpartum care , especially psychological aspects of care . Of these women , 63 percent thought that the antenatal care had raised their self-esteem , versus 18 percent of the control group . Eighty-nine percent of the experimental group would prefer birth center care for any future birth , and 46 percent of the control group would prefer st and ard care . Birth center care successfully meets the needs of women who are interested in natural childbirth and active involvement in their own care , and are concerned about the psychological aspects of birth Objective : The midwifery service at our hospital has been observed to have a 2 % cesarean birth rate consistently over a 10-year period . There are substantial differences in labor management style between the midwives and physicians . We sought to test the hypothesis that the low cesarean birth rate on the midwifery service was the result of patient selection bias . Methods : A r and omized blinded clinical trial was conducted in which 492 low-risk patients were assigned to either physician or midwifery management . The provider responsible for labor management was unable to determine group assignment . Patients in the midwifery group were managed by previously established protocol s , and outcome was attributed to the midwives even if the patients subsequently required transfer to physician management . Route of delivery was the primary outcome measurement . Continuous variables were analyzed using Student t test and discrete variables using x2 . Results : There were no demographic differences between the groups , and the admission pelvic examinations were the same . The patients assigned to the midwifery group had a 2.1 % cesarean birth rate , whereas those assigned to physician management had a 0.4 % rate . The higher rate of operative vaginal deliveries in the physician group was statistically significant . There were no differences in neonatal outcomes . The physician-managed group had significantly more episiotomies and third- and fourth-degree extensions . Conclusions : The 2 % cesarean birth rate observed on the midwifery service appeared to be the result of patient selection bias . A low cesarean birth rate can be achieved by either physician or midwifery management in a selected low-risk population OBJECTIVE to investigate whether there are differences between the cost of intrapartum care for women at low obstetric risk in a midwife-managed labour and delivery unit and that in a consultant-led labour and delivery ward . DESIGN cost analysis based on the findings of a r and omised controlled trial comparing two alternative types of intrapartum care . SETTING Aberdeen Maternity Hospital , Grampian . SUBJECTS the number of women ' booked ' for care in the Midwives ' Unit in a st and ard year and a comparable group of women cared for in the consultant-led labour ward . PRIMARY OUTCOME MEASURE the cost ' outcome ' is the extra ( or reduced ) cost per woman result ing from the introduction of a midwife-managed delivery unit . FINDINGS the baseline extra cost of the introduction of the Midwives ' Unit was found to be 40.71 pounds per woman . Depending on the scenario used , this ranged from a cost saving of 9.74 pounds per woman to an additional cost of 44.23 pounds per woman . CONCLUSIONS this study has shown that , in terms of costs incurred during the intrapartum period , the marginal cost of caring for women at low obstetric risk alongside women at high obstetric risk in a st and ard labour ward is small . However , the impact of establishing a separate midwife-managed delivery unit , requiring an increase in midwifery staffing levels , can be significant BACKGROUND Nearly all hospitalized laboring women spend most of the time in bed . We made simple but radical modifications to a hospital labor room , which included the removal of the st and ard hospital bed and the addition of equipment to promote relaxation , mobility , and calm . We design ed a pilot study , the objectives of which were to test the feasibility of a r and omized trial and the acceptability of the modified labor room to women and their care providers . METHODS Women were assessed and invited to participate just before their admission to the labor and delivery suite . Sixty-two women at two Toronto teaching hospitals were r and omly allocated to either the st and ard labor room or the " ambient room . " Data about labor and birth events were abstract ed from the medical records . Participants and their nurses and physicians completed question naires to elicit their views of their experiences with the labor rooms . RESULTS Women 's and practitioners ' evaluations of the ambient room were generally very positive . Nineteen women ( 65.5 % ) in the ambient group , compared with 4 ( 13.3 % ) in the st and ard group , reported spending 50 percent or less of their hospital labor in the st and ard labor bed . Twelve women allocated to the ambient room had artificial oxytocin infusions , compared with 21 allocated to the st and ard room ( X ( 2 ) = 4.73 , p = 0.03 ) . CONCLUSION We conclude that the ambient labor room should be evaluated in an adequately powered r and omized controlled trial A controlled clinical trial was carried out to assess whether a birth room setting would influence the care of mothers and newborns . Of the 163 low-risk women enrolled , 49 ( 30 % ) manifested some prenatal risk and were excluded . The remaining 114 were allocated by strict alternation to a birth room or a conventional setting . Of the 56 women allocated to the birth room , 63 % of the primiparas and 19 % of the multiparas were later transferred . The numbers in the two setting s who had oxytocin stimulation , epidural anesthesia , forceps delivery or cesarean section did not show statistically significant differences . The episiotomy rates were slightly lower in the birth room than in the conventional setting , and the rates of an intact perineum were higher in the birth room . Neither the Apgar scores nor the morbidity rates of the infants showed statistically significant differences related to the setting to which the mother had been allocated , although more infants from the conventional setting were admitted to a special care unit . Both " experimental " groups of women less often received routine perineal shaving , enemas or intravenous infusions than did an obstetrically similar nonexperimental comparison group . Despite the apparent inability in this setting for the birth room to influence the rate of major obstetric procedures ( except for episiotomy ) and outcomes , the authors believe that a birth room is desirable in tertiary care centres as well as in community hospitals Objective 1 . To explore whether there are differences in women 's satisfaction with care Output:	There was no apparent effect on other adverse maternal or neonatal outcomes . Care by the same or separate staff had no apparent effects . Hospital birth centres are associated with lower rates of medical interventions during labour and birth and higher levels of satisfaction , without increasing risk to mothers or babies
MS21828	*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: Vietnamese Americans are a rapidly growing minority group in the United States , yet little is known about their health status . Chronic medical conditions and self-rated health of older Vietnamese Americans were compared with those of non-Hispanic white adults living in California using the 2001 and 2003 California Health Interview Surveys ( CHISs ) . The CHIS employed a r and om-digit-dial telephone survey , and its sample is representative of California 's noninstitutionalized population . The sample included 359 Vietnamese and 25,177 non-Hispanic white adults aged 55 and older . Vietnamese and non-Hispanic white adults were compared in terms of limitations in activities of daily living , chronic medical conditions ( diabetes mellitus , hypertension , heart disease , asthma ) , mental health care , and self-reported health , adjusting for age , sex , and education . Vietnamese were more likely than white participants to report needing help for mental health problems ( adjusted odds ratio (aOR)=2.1 , 95 % confidence interval (CI)=1.4 - 3.1 ) but less likely to have had their medical providers discuss their mental health problems with them ( aOR=0.3 , 95 % CI=0.1 - 0.5 ) . In addition , Vietnamese participants reported significantly worse health than white adults on five of eight domains of the Medical Outcomes Survery 12-item Short Form survey ( P<.006 ) . Clinicians caring for older Vietnamese individuals should be aware of the high risk for mental health needs in this population and should initiate discussion s about mental health with their patients . Further research is needed to better underst and why older Vietnamese Americans are at higher risk for worse self-reported health than older white adults OBJECTIVE Despite the importance of self-management support ( SMS ) , few studies have compared SMS interventions , involved diverse population s , or entailed implementation in safety net setting s. We examined the effects of two SMS strategies across outcomes corresponding to the Chronic Care Model . RESEARCH DESIGN AND METHODS A total of 339 out patients with poorly controlled diabetes from county-run clinics were enrolled in a three-arm trial . Participants , more than half of whom spoke limited English , were uninsured , and /or had less than a high school education , were r and omly assigned to usual care , interactive weekly automated telephone self-management support with nurse follow-up ( ATSM ) , or monthly group medical visits with physician and health educator facilitation ( GMV ) . We measured 1-year changes in structure ( Patient Assessment of Chronic Illness Care [ PACIC ] ) , communication processes ( Interpersonal Processes of Care [ IPC ] ) , and outcomes ( behavioral , functional , and metabolic ) . RESULTS Compared with the usual care group , the ATSM and GMV groups showed improvements in PACIC , with effect sizes of 0.48 and 0.50 , respectively ( P < 0.01 ) . Only the ATSM group showed improvements in IPC ( effect sizes 0.40 vs. usual care and 0.25 vs. GMV , P < 0.05 ) . Both SMS arms showed improvements in self-management behavior versus the usual care arm ( P < 0.05 ) , with gains being greater for the ATSM group than for the GMV group ( effect size 0.27 , P = 0.02 ) . The ATSM group had fewer bed days per month than the usual care group ( −1.7 days , P = 0.05 ) and the GMV group ( −2.3 days , P < 0.01 ) and less interference with daily activities than the usual care group ( odds ratio 0.37 , P = 0.02 ) . We observed no differences in A1C change . CONCLUSIONS Patient-centered SMS improves certain aspects of diabetes care and positively influences self-management behavior . ATSM seems to be a more effective communication vehicle than GMV in improving behavior and quality of life OBJECTIVE To examine the relationship between communication skills training for patients and their compliance with recommended treatment . DESIGN A r and omized control design was used , with patients nested within physicians . Each physician was audiotaped with 6 patients , 2 patients in each of the 3 intervention conditions : ( 1 ) a trained group ( n = 50 ) received a training booklet in the mail 2 to 3 days prior to the scheduled appointment , ( 2 ) an informed group ( n = 49 ) received a brief written summary of the major points contained in the training booklet while in the waiting room prior to the scheduled appointment , and ( 3 ) an untrained group ( n = 51 ) did not receive any form of communication skills intervention . SETTING Participants included physicians and patients from 9 different primary care , family practice locations . Two locations were clinics associated with a large , university-based medical school and hospital , while 7 were private practice offices in the community . PARTICIPANTS The sample included 25 family physicians ( averaging 11 years postresidency ) and 150 patients . Patients were r and omly selected from appointment records and r and omly assigned to 1 of 3 intervention conditions . INTERVENTION A training booklet design ed to instruct patients in information seeking , provision , and verification . MAIN OUTCOME MEASURE Patients ' compliance with medications , behavioral treatment ( e.g. , diet , exercise , smoking cessation ) , and /or follow-up appointments and referrals . RESULTS Trained patients were more compliant overall than untrained or informed patients . Training positively influenced compliance with behavioral treatments and follow-up appointments and referrals . CONCLUSION Training patients in communication skills may be a cost-effective way of increasing compliance and improving the overall health of patients Abstract OBJECTIVE : To examine how Asian race/ethnicity affects patients ’ health care experiences and satisfaction with care . DESIGN : Telephone interview using r and om-digit dialing , stratified to over- sample adults living in areas with disproportionately large numbers of minorities . PARTICIPANTS AND SETTING : White ( N=3,205 ) and Asian-American ( N=521 ) respondents , weighted to represent all such adults living in the continental U.S. in telephone households . MEASUREMENTS : Reports of health care experiences and trust in the doctor at the last visit , and overall satisfaction with care and desire to change doctors in the last 2 years . MAIN RESULTS : Asian Americans were less likely than whites to report that their doctors ever talked to them about lifestyle or mental health issues ( P≤.01 ) . They were more likely to report that their regular doctors did not underst and their background and values ( P≤.01 ) . When asked about the last visit , they were more likely to report that their doctors did not listen , spend as much time , or involve them in decisions about care as much as they wanted ( all P≤.0001 ) . In multivariable analyses , Asian Americans were less likely than whites to report that they were very satisfied with care ( odds ratio [ OR ] , 0.64 , 95 % confidence interval [ CI ] , 0.42 to 0.99 ) . However , they were not significantly less likely than whites to trust their doctors ( OR , 0.79 , 95 % CI , 0.52 to 1.20 ) , or to change doctors ( OR , 0.93 , 95 % CI , 0.56 to 1.56 ) . CONCLUSIONS : In a national survey , Asian Americans were less likely to receive counseling and less likely to report positive interactions with their doctors than white respondents . More research is needed to determine the reasons for these differences Research on physician-patient communication has focused on the effect of physician communication training on health care outcomes . Much less is known about patient communication training , and even less about the impact of patient race on the effectiveness of patient communication interventions . One hundred and fifty patients of 25 family physicians were r and omly assigned to one of three groups : 14-page patient communication workbook received 2 - 3 days pre-visit , 2-page patient communication h and out received in the waiting room , or control group . Racial differences in the impact of patient communication training communication variables , immediate and delayed recall of information , and adherence to treatment were analyzed by t-test and ANOVA techniques . Across analyses , workbook communication skills training had a strong and significant effect on white patients but minimal or no effect on African-American patients . Minimal differences in dependent variables between racial groups existed for the patient h and out and control groups . A partial correlation analysis was conducted to factor out the variance due to education . Results suggested that patient race accounted for the results over and above differences in education between racial groups . Our results suggested that the benefits of communication training can be enhanced by taking into account patient characteristics such as race and culture CONTEXT Pneumococcal immunization rates for elderly and high-risk patients are only one third to one half the target rate of 60 % established by the US Public Health Service . Limited or marginal literacy , which affects nearly 100 million Americans , especially the elderly , may contribute to these low rates of immunization . OBJECTIVE To determine whether the use of a simple , low-literacy educational tool enhances patient-physician dialogue about pneumococcal vaccination and increases rates of immunization . DESIGN A r and omized controlled trial conducted between May and June of 1998 . SETTING Ambulatory care clinic of a 900-bed public teaching hospital serving a predominantly indigent , low-literate , African American , inner-city population . PARTICIPANTS Of 433 patients who presented for routine primary care , had vaccine indications ( age > or = 65 years or chronic disease ) , and had not been previously vaccinated , 221 were r and omly assigned to the intervention group and 212 to the control group . Of the total patient population ( mean age , 63 years ) , 280 ( 64.7 % ) had less than a high school education , 401 ( 92.6 % ) were African American , and 300 ( 69.3 % ) were female . INTERVENTION One-page , low-literacy ( below fifth- grade level ) educational h and out encouraging patients to " ask your doctor about the pneumonia shot " vs a control group ( 1 -page , low-literacy educational h and out conveying information about nutrition ) . MAIN OUTCOME MEASURES Vaccination rates ( documented by chart audit ) of patients who received pneumococcal vaccination and rates of patients who self-reported having discussed vaccination with their physicians . RESULTS Patients in the intervention group were 4 times more likely to have discussed the pneumococcal vaccine with their physicians than patients in the control group ( 87/221 [ 39.4 % ] vs 21/212 [ 9.9 % ] ; relative risk [ RR ] , 3.97 [ 95 % confidence interval [ CI ] , 2.71 - 5.83 ] ) , and were more than 5 times as likely to have received the pneumococcal vaccine than the control group ( 44/221 [ 19.9 % ] vs 8/212 [ 3.8 % ] ; RR , 5.28 [ 95 % CI , 2.80 - 9.93 ] ) . In a multivariate analysis controlling for race , sex , education , insurance status , age , level of physician training , health status , and vaccine indication , only assignment to the intervention group was statistically significantly related to the probability of being immunized or discussing the issue with their physicians ( P<.001 for both trends ) . CONCLUSIONS A simple , low-literacy educational tool increased pneumococcal vaccination rates and patient-physician discussion s about the vaccine in an elderly , low-literate , indigent , minority population It is important for patients to provide relevant information to the doctor in consultation and to make their own information requirements known . This requires patients to actively participate in the process , something they appear to be reluctant to do . Earlier patient intervention studies have successfully manipulated patient involvement and question asking , although , the latter has tended to be accompanied by increased tension and negative impact . The present study uses a patient education leaflet which uses a wide definition of patient activation . It emphasizes the role of the ' good ' patient as a provider of information extending beyond the recitation of symptoms to include insights to interpretation and meaning . Results showed that patients responded positively to the leaflet and a comparison of doctor ratings of communication quality showed the experimental group performed better than the controls . The findings are considered in terms of improved information exchange and the impact of making the ' rules ' of consultation explicit is also discussed BACKGROUND Active participation and asking questions are important ways in which patients can ensure they underst and what the doctor has said . This study evaluated a question prompt sheet design ed to encourage patients to ask questions in the cancer consultation . PATIENTS AND METHODS Patients ( n = 142 ) were r and omised to receive ( i ) a question prompt sheet or ( ii ) a general sheet informing patients of services available through the regional Cancer Council . Recall of information was assessed in a structured interview 4 - 20 days after the consultation . Question naires to assess patient satisfaction and adjustment to cancer were sent by mail . RESULTS The question prompt sheet had a significant effect in one content area : prognosis . Thirty-five percent of patients who received the question h and out asked questions about prognosis compared to 16 % of those receiving the information h and out . The prompt sheet did not increase the mean number of questions asked overall . Age , in/out-patient status , gender and involvement preference were predictive of both number and duration of patient questions . CONCLUSIONS A question prompt sheet has a limited but important effect on patient question asking behaviour in the cancer consultation This study examined the efficacy of a brief written intervention for primary care patients , design ed to increase their level of participation in the consultation . Patients given the intervention leaflet ( N = 59 ) were compared with those given a control leaflet ( N = 61 ) on various consultation process and outcome measures . Psychological and sociodemographic data were also obtained to determine whether these influenced the effects of the intervention . The results showed that the intervention group had significantly longer consultations and asked more questions than the controls . Younger patients and those from social classes 1 and 2 were more likely to benefit from Output:	Interventions ranged from a leaflet encouraging patients to ask more questions , to more intensive face-to-face coaching before office visits .
MS21829	*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 : Patients with functional dyspepsia who have hypersensitivity to gastric distension have more prevalent pain , suggesting the presence of hyperalgesia . It is unclear whether this reflects activation of pain specific afferent pathways or multimodal afferent pathways that also mediate non-painful sensations . In the former case , hyperalgesia should occur when intensity of non-painful sensations is still low . The aim of the study was to analyse whether the symptom profile during gastric dissentions in functional dyspepsia patients with hyperalgesia reflects sensitisation of pain specific or multimodal pathways . Methods : Forty eight consecutive dyspeptic patients ( 35 female ) underwent gastric sensitivity testing with a barostat balloon using a double r and om staircase protocol . At the end of every distending step , patients scored perception of upper abdominal sensations on a graphic 0–6 rating scale and completed visual analogue scales ( VAS 0–100 mm ) for pain , nausea , satiety , and fullness . The end point was a rating scale of 5 or more . Results : Hypersensitivity was present in 20 patients ( 40 % ) ; gastric compliance did not differ between normo- and hypersensitive patients . At maximal distension ( score 5 or more ) , hypersensitive patients had significantly lower distending pressures and intra-balloon volumes , but similar VAS scores for pain , nausea , satiety , and fullness compared with normosensitive patients . In both normosensitive and hypersensitive patients , elevation of pain VAS scores with increasing distending pressures paralleled the elevation in VAS scores for nausea , satiety , and fullness . Conclusions : Hypersensitive dyspeptic patients reach the same intensity of painful and non-painful sensations as normosensitive patients but at lower distending pressures . Hyperalgesia occurs in hypersensitive dyspeptic patients at distending pressures that also induce intense non-painful sensations . These findings argue against isolated upregulation of pain specific afferents in functional dyspepsia patients with visceral hypersensitivity OBJECTIVE To evaluate the association between functional gastrointestinal ( GI ) symptoms and a family history of abdominal pain or bowel problems . SUBJECTS AND METHODS A valid self-report question naire that records GI symptoms and spouse 's and first-degree relatives ' history of abdominal pain or bowel troubles and includes the psychosomatic symptom checklist ( a measure of somatization ) was mailed to an age- and sex-stratified r and om sample of Olmsted County , Minnesota , residents aged 30 to 64 years . A logistic regression model that adjusted for age , sex , and somatic symptom score was used to estimate the odds ratio ( OR ) and 95 % confidence interval ( CI ) of a positive family history for each functional GI disorder . RESULTS Six hundred forty-three ( 72 % ) of 892 eligible subjects returned the survey . Reporting a first-degree relative with abdominal pain or bowel problems was significantly associated with reporting of irritable bowel syndrome ( OR , 2.3 ; 95 % CI , 1.3 - 3.9 ) and dyspepsia ( OR , 1.8 ; 95 % CI , 1.05 - 3.0 ) but not constipation , diarrhea , or gastroesophageal reflux . The reporting of a spouse with abdominal pain or bowel problems was not associated with any of these disorders . CONCLUSIONS A history of abdominal pain or bowel troubles in first-degree relatives was significantly associated with irritable bowel syndrome and dyspepsia . Whether the familial associations represent similar exposures in a shared environment , heightened familial awareness of GI symptoms ( reporting bias ) , or genetic factors remains to be determined BACKGROUND / AIMS Dyspepsia and gastroesophageal reflux disease are common chronic diseases . In the clinical setting , some patients express both problems together ; however , little is known about the real prevalence of the presence of the two symptoms . Turkey is particularly interesting because of differences observed from developed countries . We aim ed to derive data from our previous prevalence of gastroesophageal reflux disease study and evaluate the overlap of the two symptoms . METHODS We used a previously vali date d and culturally adapted reflux question naire , which was translated into Turkish . The question naire was applied to 630 r and omly selected subjects older than 20 years living in a population of 8857 adults . RESULTS 28.6 % ( 180/630 ) of all responders defined dyspepsia within the last 12-month period . When symptom prevalence was considered at least weekly , the prevalence was 10 % for heartburn , 15.6 % for acid regurgitation , and 20 % for either symptom . While the prevalence of gastroesophageal reflux disease was 29.4 % in patients with dyspepsia , dyspepsia was found in 43.1 % of patients with gastroesophageal reflux disease . Only 21 % of symptomatic subjects or 8.4 % of the entire study population had both symptoms . Dyspepsia was defined as the most bothersome symptom . 54.3 % of all dyspeptic patients and 67.3 % with both gastroesophageal reflux disease and dyspepsia used a gastric medication ( p>0.05 ) . 29.9 % of subjects with dyspeptic symptoms defined antacid consumption and 28.3 % acid inhibitor therapy . CONCLUSION Dyspepsia was defined as the most bothersome symptom compared to gastroesophageal reflux disease symptoms . The prevalence of dyspepsia in patients with gastroesophageal reflux disease is more common than vice versa . However , the overlap of the two symptom groups was lower than expected in this low-income , Caucasian population BACKGROUND AND STUDY AIMS Gastro-oesophageal reflux disease ( GERD ) and dyspepsia are common digestive disorders that inflict serious harm , burden and economic consequences on individuals worldwide . The aim of this study was to estimate the direct and indirect economic burden of GERD and dyspepsia in the whole population of Tehran , the capital of Iran . PATIENTS AND METHODS The study was performed on a total of 18,180 adult subjects ( age>18 years ) taken as a r and om sample in Tehran province , Iran ( 2006 - 2007 ) . A valid and reliable question naire was used to enquire about the symptoms of GERD , dyspepsia and the frequency of the utilization of health services including physician visits , hospitalisations and productivity loss due to GERD/dyspepsia symptoms in the preceding 6 months . RESULTS GERD was found in 518 ( 41.9 % males ) patients and dyspepsia in 404 patients ( 38.9 % males ) . Further 1007 subjects had both GERD and dyspepsia . The total direct costs of disease per patient for GERD , dyspepsia and their overlap were PPP$97.70 , PPP$108.10 and PPP$101.30 , respectively ( PPP , purchasing power parity dollars ) . The total indirect cost of disease per patient was PPP$13.7 , PPP$12.1 and PPP$32.7 , for GERD , dyspepsia and their overlap , respectively . CONCLUSION According to our results , hospitalisation and physician visits were the main cost of disease that could be minimised by revision of the insurance business in Iran BACKGROUND & AIMS Hypersensitivity to proximal gastric distention as a result of abnormal central nervous system processing of visceral stimuli is a possible pathophysiologic mechanism in functional dyspepsia ( FD ) . Increasing evidence suggests involvement of both lateral and medial pain systems in normal visceral sensitivity and aberrant brain activation patterns in visceral hypersensitivity . We hypothesized that there is involvement of aberrant brain activation in FD with hypersensitivity to gastric distention . Our aim was to investigate regional cerebral blood flow during painful proximal gastric distention in hypersensitive FD . METHODS Brain (15)O-water positron emission tomography was performed in 13 FD patients with symptoms of gastric hypersensitivity during 3 conditions : no distention , sham distention , and isobaric distention to unpleasant or painful sensation . Pain , discomfort , nausea , and bloating during maximal distention were rated on visual analogue scales . Data were analyzed using statistical parametric mapping . RESULTS The threshold for painful distention was 6.6 + /- 3.8 mm Hg greater than the minimal distending pressure . At the corrected P level of less than .05 , subtraction analysis ( painful distention - no distention ) showed activations in bilateral gyrus pre central is , bilateral gyrus frontalis inferior , bilateral gyrus frontalis medialis , bilateral gyrus temporalis superior , bilateral cerebellar hemisphere , and left gyrus temporalis inferior . Sham distention minus no distention showed no activations . CONCLUSIONS Similar to healthy volunteers , proximal stomach distention in FD activates components of the lateral pain system and bilateral frontal inferior gyri , putatively involved in regulation of hunger and satiety . In hypersensitive FD , these activations occur at significantly lower distention pressures . In contrast to findings in normosensitivity , none of the components of the medial pain system were significantly activated BACKGROUND : The heterogeneity of the dyspepsia symptom complex is well known . Several attempts to classify dyspepsia into subgroups have been proposed as a basis for diagnosis and therapy , but data are conflicting . We postulated that dyspepsia comprises three distinct subsets , characterized by pain , early satiety , or nausea/vomiting . We aim ed to identify these subsets of dyspepsia : “ frequent upper abdominal pain ( UAP ) , ” “ early satiety ( ES ) , ” and “ nausea/vomiting ( NV ) . ” METHODS : A population -based , cross-sectional survey study was conducted by mailing a valid question naire to an age- and gender-stratified r and om sample of residents of Olmsted County , MN , aged 20–94 yr ( response rate 55 % ) . Dyspepsia and irritable bowel syndrome ( IBS ) prevalence were estimated by Rome II criteria ; gastroesophageal reflux ( GERD ) by weekly or more frequent heartburn or acid regurgitation . Dyspepsia subgroups were categorized based on a priori defined symptoms . RESULTS : The prevalence ( 95 % CI ) of dyspepsia was 15 % ( 14 , 17 ) . Of 351 dyspeptic subjects , 51 % ( 46 , 56 ) reported UAP , 21 % ( 16 , 25 ) NV , and 47 % ( 42 , 52 ) ES . The overlap of the subgroups was significantly less than expected by chance . Among the three groups , the subjects were similar in age , educational level , IBS status , and overall symptom severity . A high somatic symptom checklist score and those with GERD were associated with greater odds for reporting combination symptoms compared with the upper abdominal pain subgroup of dyspepsia or the early satiety subgroup of dyspepsia , respectively . CONCLUSION : Distinct subgroups of uninvestigated dyspepsia do exist in the general population , suggesting that separate evaluation and treatment strategies are needed OBJECTIVE : Upper gastrointestinal disorders are common in the community , yet the determinants of these symptoms are poorly characterized . The association between upper gastrointestinal symptoms and Helicobacter pylori ( H. pylori ) , socioeconomic status , nonsteroidal antiinflammatory drug ( NSAID ) use , smoking , alcohol , and coffee intake was assessed in a cross-sectional survey . METHODS : Subjects between the ages of 40–49 yr were r and omly selected from the lists of 36 primary care centers . Participants attended their local primary care center and were interviewed by a research er using a vali date d dyspepsia question naire . H. pylori status was determined by a nonfasting 13C-urea breath test . RESULTS : A total of 32,929 subjects were invited , and 8,407 ( 25 % ) attended and were eligible . Of these , 2,329 ( 28 % ) were H. pylori positive and 3,177 ( 38 % ) had dyspepsia . Also , 44 % of H. pylori-infected participants reported dyspepsia compared with 36 % of uninfected subjects [ odds ratio = 1.39 ; 95 % confidence interval ( CI ) 1.26–1.53 ] . H. pylori infection remained a significant risk factor for dyspepsia in a multiple logistic regression model ( odds ratio = 1.21 ; 95 % CI 1.09–1.34 ) , suggesting that 5 % of dyspepsia in the population is attributable to H. pylori . NSAIDs , low educational attainment , renting accommodation , absence of central heating , sharing a bed with siblings , and being married were also significantly associated with dyspepsia in this model . Smoking , but not drinking alcohol or coffee , was marginally associated with dyspepsia , but this finding was not robust . These factors were not associated with any dyspepsia subtype . CONCLUSIONS : H. pylori is significantly associated with dyspepsia and may be responsible for 5 % of upper gastrointestinal sympt Output:	The OR for dyspepsia in individuals with weekly GERS was significantly higher in all geographical regions studied and for all diagnostic criteria . : The odds of dyspepsia in individuals with weekly GERS is almost 7‐fold that of individuals without GERS ; dyspepsia and GERS overlap in more than 25 % of individuals .
MS21830	*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 purpose of this study was to evaluate the effect of a physical activity telemonitoring program on daily physical activity level , oxygen uptake capacity ( VO2peak ) , and cardiovascular risk profile in coronary artery disease ( CAD ) patients who completed phase II cardiac rehabilitation ( CR ) . Methods Eighty CAD patients who completed phase II CR were r and omly assigned to an additional telemonitoring intervention or st and ard CR . The patients in the intervention group ( n = 40 ) wore a motion sensor continuously for 18 weeks . Each week these patients received a step count goal , with the aim to gradually increase the patients ’ physical activity level . In the control group ( n = 40 ) , the patients wore an unreadable motion sensor for seven days for measurement purpose s only ( at start of follow-up , and after six and 18 weeks ) . At start of follow-up and after 18 weeks blood lipid profile , glycemic control , waist circumference and body mass index was assessed . VO2peak was assessed at start of follow-up , and after six and 18 weeks . Re-hospitalisation rate was followed during this timeframe . Results In the intervention group , VO2peak increased significantly during follow-up ( P = 0.001 ) , in the control group it did not ( P = 0.273 ) . A significant correlation was found between daily aerobic step count and improvement in VO2peak ( P = 0.030 , r = 0.47 ) . Kaplan-Meier curve analysis showed a trend towards fewer re-hospitalisations for patients in the telemonitoring group ( P = 0.09 ) . Conclusions The study showed that , to maintain exercise tolerance and lower re-hospitalisation rate after hospital-based CR in CAD patients , a physical activity telemonitoring program might be an effective intervention Background Smartphone manufacturers offer mobile health monitoring technology to their customers , including apps using the built-in camera for heart rate assessment . This study aim ed to test the diagnostic accuracy of such heart rate measuring apps in clinical practice . Methods The feasibility and accuracy of measuring heart rate was tested on four commercially available apps using both iPhone 4 and iPhone 5 . ‘ Instant Heart Rate ’ ( IHR ) and ‘ Heart Fitness ’ ( HF ) work with contact photoplethysmography ( contact of fingertip to built-in camera ) , while ‘ What s My Heart Rate ’ ( WMH ) and ‘ Cardiio Version ’ ( CAR ) work with non-contact photoplethysmography . The measurements were compared to electrocardiogram and pulse oximetry-derived heart rate . Results Heart rate measurement using app-based photoplethysmography was performed on 108 r and omly selected patients . The electrocardiogram-derived heart rate correlated well with pulse oximetry ( r = 0.92 ) , IHR ( r = 0.83 ) and HF ( r = 0.96 ) , but somewhat less with WMH ( r = 0.62 ) and CAR ( r = 0.60 ) . The accuracy of app-measured heart rate as compared to electrocardiogram , reported as mean absolute error ( in bpm ± st and ard error ) was 2 ± 0.35 ( pulse oximetry ) , 4.5 ± 1.1 ( IHR ) , 2 ± 0.5 ( HF ) , 7.1 ± 1.4 ( WMH ) and 8.1 ± 1.4 ( CAR ) . Conclusions We found substantial performance differences between the four studied heart rate measuring apps . The two contact photoplethysmography-based apps had higher feasibility and better accuracy for heart rate measurement than the two non-contact photoplethysmography-based apps Background In contrast to the well-accepted benefits of moderate exercise , recent research has suggested potential deleterious effects of repeated marathon running on the cardiovascular system . We thus performed a comprehensive analysis of markers of sub clinical vascular damage in a cohort of runners having finished multiple marathon races successfully . Design This was a prospect i ve , observational study . Methods A total of 97 healthy male Munich marathon participants ( mean age 44 ± 10 years ) underwent detailed training history , cardiopulmonary exercise testing for assessment of peak oxygen uptake , ultrasound for assessment of intima-media-thickness as well as non-invasive assessment s of ankle-brachial index , augmentation index , pulse wave velocity and reactive hyperaemia index . Results Runners had previously completed a median of eight ( range 1–500 ) half marathons , six ( 1–100 ) full marathons and three ( 1–40 ) ultramarathons ; mean weekly and annual training volumes were 59 ± 23 and 1639 ± 979 km . Mean peak oxygen uptake was 50 ± 8 ml/min/kg , and the Munich marathon was finished in 3:45 ± 0:32 h. Runners showed normal mean values for intima-media-thickness ( 0.60 ± 0.14 mm ) , ankle-brachial index ( 1.2 ± 0.1 ) , augmentation index ( 17 ± 13 % ) , pulse wave velocity ( 8.7 ± 1.4 cm/s ) and reactive hyperaemia index ( 1.96 ± 0.50 ) . Age was significantly and independently associated with intima-media-thickness ( r = 0.531 ; p < 0.001 ) , augmentation index ( r = 0.593 ; p < 0.001 ) and pulse wave velocity ( r = 0.357 ; p < 0.001 ) . However , no independent associations of peak oxygen uptake , marathon finishing time , number of completed races or weekly and annual training km with any of the vascular parameters were observed . Conclusions In this cohort of healthy male runners , running multiple marathon races did not pose an additional risk factor for premature sub clinical vascular impairment beyond age Aim Although cardiac rehabilitation improves physical fitness after a cardiac event , many eligible patients do not participate in cardiac rehabilitation and the beneficial effects of cardiac rehabilitation are often not maintained over time . Home-based training with telemonitoring guidance could improve participation rates and enhance long-term effectiveness . Methods and results We r and omised 90 low-to-moderate cardiac risk patients entering cardiac rehabilitation to three months of either home-based training with telemonitoring guidance or centre-based training . Although training adherence was similar between groups , satisfaction was higher in the home-based group ( p = 0.02 ) . Physical fitness improved at discharge ( p < 0.01 ) and at one-year follow-up ( p < 0.01 ) in both groups , without differences between groups ( home-based p = 0.31 and centre-based p = 0.87 ) . Physical activity levels did not change during the one-year study period ( centre-based p = 0.38 , home-based p = 0.80 ) . Healthcare costs were statistically non-significantly lower in the home-based group ( € 437 per patient , 95 % confidence interval –562 to 1436 , p = 0.39 ) . From a societal perspective , a statistically non-significant difference of € 3160 per patient in favour of the home-based group was found ( 95 % confidence interval –460 to 6780 , p = 0.09 ) and the probability that it was more cost-effective varied between 97 % and 75 % ( willingness-to-pay of € 0 and € 100,000 per quality -adjusted life-years , respectively ) . Conclusion We found no differences between home-based training with telemonitoring guidance and centre-based training on physical fitness , physical activity level or health-related quality of life . However , home-based training was associated with a higher patient satisfaction and appears to be more cost-effective than centre-based training . We conclude that home-based training with telemonitoring guidance can be used as an alternative to centre-based training for low-to-moderate cardiac risk patients entering cardiac rehabilitation Background Exercise training as part of a comprehensive cardiac rehabilitation is recommended for patients with cardiac heart failure . It is a valuable method for the improvement of exercise tolerance . Some studies reported a similar improvement with quadricipital electrical myostimulation , but the effect of combined exercise training and electrical myostimulation in cardiac heart failure has not been yet evaluated in a large prospect i ve multicentre study . Purpose The aim of this study was to determine whether the addition of low frequency electrical myostimulation to exercise training may improve exercise capacity and /or muscular strength in cardiac heart failure patients . Methods Ninety-one patients were included ( mean age : 58 ± 9 years ; New York Heart Association II/III : 52/48 % , left ventricular ejection fraction : 30 ± 7 % ) in a prospect i ve French study . The patients were r and omised into two groups : 41 patients in exercise training and 50 in exercise training + electrical myostimulation . All patients underwent 20 exercise training sessions . In addition , in the exercise training + electrical myostimulation group , patients underwent 20 low frequency ( 10 Hz ) quadricipital electrical myostimulation sessions . Each patient underwent a cardiopulmonary exercise test , a six-minute walk test , a muscular function evaluation and a quality of life question naire , before and at the end of the study . Results A significant improvement of exercise capacity ( Δ peak oxygen uptake+15 % in exercise training group and + 14 % in exercise training + electrical myostimulation group ) and of quality of life was observed in both groups without statistically significant differences between the two groups . Mean creatine kinase level increased in the exercise training group whereas it remained stable in the combined group . Conclusions This prospect i ve multicentre study shows that electrical myostimulation on top of exercise training does not demonstrate any significant additional improvement in exercise capacity in cardiac heart failure patients Background Exercise training is an established modality in chronic heart failure . Functional electrical stimulation ( FES ) is an effective alternative mode of training in patients unwilling or unable to exercise ; however , it has not been investigated in elderly patients . We sought to investigate the effects of FES on functional status , quality of life , emotional status and endothelial function in chronic heart failure patients aged 70 years or higher . Methods Thirty patients with stable systolic chronic heart failure ( mean age 75 ± 3 years , New York Heart Association ( NYHA ) class II/III , 37%/63 % ) r and omly underwent a six-week FES training programme or placebo . Question naires addressing quality of life ( Kansas City Cardiomyopathy Question naire ( KCCQ ) , functional and overall ) and emotional stress ( Zung self-rating depression scale ( SDS ) , Beck Depression Inventory ( BDI ) ) , as well as endothelial function ( flow-mediated dilatation ) were assessed at baseline and upon protocol completion . Results A significant improvement in NYHA class ( p = 0.005 ) , KCCQ-functional ( F = 68.6 , p for interaction < 0.001 ) , KCCQ-overall ( F = 66.9 , p < 0.001 ) , BDI ( F = 66.3 , p < 0.001 ) and Zung SDS ( F = 95.1 , p < 0.001 ) was observed in the FES group compared to placebo . Patients in the FES group also had a significant increase in flow-mediated dilatation compared with placebo ( F = 59.1 , p < 0.01 ) . FES-induced per cent change in flow-mediated dilatation was significantly correlated with respective per cent change in KCCQ functional ( r = 0.386 , p = 0.039 ) . Conclusion In this pilot study , FES effectively improved functional status , quality of life , motional stress and endothelial function in elderly chronic heart failure patients and warrants further investigation in this particular group of patients Output:	No differences between home-based training with telemonitoring control guidance and centre-based training on physical fitness , physical activity level or health-related quality of life have been observed . Instead , home-based training was associated with greater patient satisfaction and appears to be more cost-effective than centre-based training . In the above group , heart rate was monitored by a chest strap and data were uploaded to a web application , allowing the patient , therapist and exercise specialist to review the data . Thus home-based training with telemonitoring guidance can be used as an alternative to centre-based training for low-to-moderate cardiac risk patients . Electrical myostimulation ( EMS ) on top of exercise training has no significant additional improvement in exercise capacity in heart failure patients . EMS has shown potential beneficial effects such as improvement of muscle function , exercise capacities , endothelial function and quality of life , in those patients who are unable or unwilling to adhere to conventional exercise . However , in a r and omised prospect i ve French trial , the combination of physical exercise with EMS was not associated with greater improvement in oxygen uptake or quality of life . The study population included only moderately severe and stable heart failure patients with baseline peak oxygen uptake around 16–17ml/kg/min ; thus the results may not be extrapolated to more severe patients . In a systematic review of the existing literature , progressive resistance training result ed in an increase in lower and upper body strength , and improved aerobic fitness to a similar degree as aerobic training in coronary heart disease cohorts . Importantly , when progressive resistance training was added to aerobic training , effects on both fitness and strength were enhanced compared to aerobic training alone . The two contact photoplethysmography-based apps had higher feasibility and better accuracy for heart rate measurement than the two non-contact photoplethysmography-based apps
MS21831	*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: Sodium restriction can reduce blood pressure in hypertensive patients . The present study indicates that if hypertension is well controlled then the reemergence of hypertension can be decreased by the use of a reduced sodium intake . The present paper demonstrates that in such patients on a normal salt diet , 90 % become hypertensive within 6 months while only 40 % of people on a reduced sodium diet become hypertensive . It is proposed that a high sodium intake activates a number of amplifiers that causes a shift of the dose-response curve to sodium to the left and if not prevented or interrupted leads to the development of hypertension The aim of the present study was to evaluate the effects of a normal-sodium ( 120 mmol sodium ) diet compared with a low-sodium diet ( 80 mmol sodium ) on readmissions for CHF ( congestive heart failure ) during 180 days of follow-up in compensated patients with CHF . A total of 232 compensated CHF patients ( 88 female and 144 male ; New York Heart Association class II-IV ; 55 - 83 years of age , ejection fraction < 35 % and serum creatinine < 2 mg/dl ) were r and omized into two groups : group 1 contained 118 patients ( 45 females and 73 males ) receiving a normal-sodium diet plus oral furosemide [ 250 - 500 mg , b.i.d . ( twice a day ) ] ; and group 2 contained 114 patients ( 43 females and 71 males ) receiving a low-sodium diet plus oral furosemide ( 250 - 500 mg , b.i.d . ) . The treatment was given at 30 days after discharge and for 180 days , in association with a fluid intake of 1000 ml per day . Signs of CHF , body weight , blood pressure , heart rate , laboratory parameters , ECG , echocardiogram , levels of BNP ( brain natriuretic peptide ) and aldosterone levels , and PRA ( plasma renin activity ) were examined at baseline ( 30 days after discharge ) and after 180 days . The normal-sodium group had a significant reduction ( P<0.05 ) in readmissions . BNP values were lower in the normal-sodium group compared with the low sodium group ( 685+/-255 compared with 425+/-125 pg/ml respectively ; P<0.0001 ) . Significant ( P<0.0001 ) increases in aldosterone and PRA were observed in the low-sodium group during follow-up , whereas the normal-sodium group had a small significant reduction ( P=0.039 ) in aldosterone levels and no significant difference in PRA . After 180 days of follow-up , aldosterone levels and PRA were significantly ( P<0.0001 ) higher in the low-sodium group . The normal-sodium group had a lower incidence of rehospitalization during follow-up and a significant decrease in plasma BNP and aldosterone levels , and PRA . The results of the present study show that a normal-sodium diet improves outcome , and sodium depletion has detrimental renal and neurohormonal effects with worse clinical outcome in compensated CHF patients . Further studies are required to determine if this is due to a high dose of diuretic or the low-sodium diet 28 patients who had a sustained diastolic blood pressure of 95 to 104 mm Hg and who had no treatment for it for at least 13 months before the trial , but who were otherwise unselected , took part in a r and omised controlled trial in which the effect of a restricted sodium diet was compared with that of a general health package . The general health package did not include any specific hypotensive procedures . Changes in blood pressure were measured at predetermined intervals over the course of a year . Within each group both systolic and diastolic blood pressure fell to a highly significant extent after a year , but there was no significant difference between the groups . It would thus seem that the antihypertensive effect of a restricted sodium diet may be related to the increased consultation and monitoring activity of such intervention rather than to the dietary manipulation itself Universal reduction in sodium intake has long been recommended , largely because of its proven ability to lower blood pressure for some . However , multiple r and omized trials have also demonstrated that similar reductions in sodium increase plasma renin activity and aldosterone secretion , insulin resistance , sympathetic nerve activity , serum cholesterol , and triglyceride levels . Thus , the health consequences of reducing sodium can not be predicted by its impact on any single physiologic characteristic but will reflect the net of conflicting effects . Some 23 observational studies ( > 360,000 subjects and > 26,000 end points ) linking sodium intake to cardiovascular outcomes have yielded conflicting results . In subjects with average sodium intakes of less than 4.5 g/day , most have found an inverse association of intake with outcome ; in subjects with average intakes greater than 4.5 g/day , most reported direct associations . Finally , in two , a " J-shaped " relation was detected . In addition , three r and omized trials have found that heart failure subjects allocated to 1.8 g of sodium have significantly increased morbidity and mortality compared with those at 2.8 g. At the same time , a r and omized study in retired Taiwanese men found that allocation to an average intake of 3.8 g improved survival compared with 5.3 g. Taken together , these data provide strong support for a " J-shaped " relation of sodium to cardiovascular outcomes . Sodium intakes above and below the range of 2.5 - 6.0 g/day are associated with increased cardiovascular risk . This robust body of evidence does not support universal reduction of sodium intake The present study set out to assess the feasibility of long-term moderate dietary sodium restriction in patients with mild hypertension in general practice . After screening and a run-in phase of 6 - 8 weeks , a total of 77 previously undiagnosed mildly hypertensive patients were identified . Half of them were r and omized to receive a few simple dietary instructions from their general practitioners in order to reduce salt usage ; the others were r and omized to receive no advice . The patients were followed up for 12 months with quarterly visits . A total of 56 patients ( 72.7 % ) completed the study , 26 on a low-sodium diet ( LD ) and 30 on their usual diet ( UD ) . At each visit in the diet phase , patients provided 24h urine , which was analysed for volume and sodium concentration in order to assess their sodium intake . Blood pressure , heart the rate and body weight were recorded . The mean urinary sodium excretion for all diet phase visits overlapped in the two groups ( 177.0 + /- 32.9 vs. 169.3 + /- 49.4 mEq/24h respectively in the LD and UD groups ) . Nevertheless the mean systolic and diastolic blood pressures for all diet phase visits were significantly lower in the LD than in UD group ( 144.2 + /- 11.1/91.6 + /- 6.4 and 148.0 + /- 13.7/95.6 + /- 4.7 mmHg respectively , P less than 0.01 ) . Our data suggest that it is not feasible at present to reduce sodium intake in mild hypertensives with simple and inexpensive dietary instructions , the only ones suitable for widespread application in general practice 1 . Three groups of young patients with borderline hypertension were studied for a 12 months period . The first was on a free sodium diet while the second was on a low-salt diet . The third group of patients underwent acute salt loading . 2 . After 12 months the group on free diet showed a significant increase of intralymphocytic sodium but no change in blood pressure was noted . Five patients who were re-checked after 24 months also had a significant increase in blood pressure . 3 . Patients treated with a low-salt diet showed a significant decrease of both intralymphocytic sodium concentration and blood pressure . 4 . After acute salt loading , borderline subjects with high intralymphocytic sodium showed a significant greater natriuresis whereas intralymphocytic sodium increased only in those subjects in whom it was initially normal Output:	Our estimates of benefits from dietary salt restriction are consistent with the predicted small effects on clinical events attributable to the small blood pressure reduction achieved
MS21832	*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: Forty patients who were scheduled for a total hip arthroplasty were enrolled in a prospect i ve study and were r and omly divided into two groups . Group 1 received recombinant human erythropoietin ( 300 U/kg twice a week ) , and group 2 received placebo . The medication was started 2 weeks before the operation , and only one dose of medication was given after the operation . Autologous blood was administered at the same time as the medication until the hemoglobin level sank to 10 g/dl . Forty-eight and 49 units of autologous blood were collected in group 1 and group 2 , respectively . Intraoperative homologous blood was transfused only to patients in group 2 . Seven and 13 units of allogenic blood were transfused into group 1 and group 2 patients during the postoperative period , respectively . There were no any significant differences between the groups in terms of early postoperative hemoglobin level and amount of autologous blood collected . However , the increase of the reticulocyte count in patients who received erythropoietin was significantly higher than in the group 2 patients . The study showed that short-term and low-dose erythropoietin usage strongly stimulates the bone marrow . Erythropoietin administration and preoperative autologous blood donation diminished the total units of allogenic blood required during the intraoperative or postoperative pe-riod . Autologous blood administration without concurrent erythropoietin did not stimulate the bone marrow adequately This prospect i ve r and omized trial compared preoperative autologous blood donation ( PAD ) with epoetin alfa in patients undergoing primary total knee reconstruction . Fifty adult patients with pretreatment hemoglobin level of 100 to 130 g/L were r and omized to either epoetin alfa 40,000 U at preoperative days 14 and 7 or to a st and ard PAD protocol . Patient characteristics and operative blood loss were similar between groups . Baseline hematological parameters for epoetin alfa vs PAD were not significantly different ; however , by the day of surgery the epoetin alfa group had significantly higher hemoglobin ( 130 vs 114 g/L ; P < .001 ) , hematocrit ( 0.408 vs 0.352 ; P < .001 ) , and reticulocyte count ( 3.4 vs 2.1 x 10(9 ) cells per liter ; P < .001 ) . These differences remained significant for 1 to 2 days postoperatively . There was no significant difference in the incidence of allogeneic transfusions between groups ( 28 % for epoetin alfa vs 8 % for PAD ; P = .1383 ) . Both treatments were generally well tolerated . Epoetin alfa appears to be a safe alternative to PAD in patients who are at risk for transfusion in the perioperative period following total knee arthroplasty In a prospect i ve r and omized study we investigated the potential of subcutaneous recombinant human erythropoietin ( rhEpo ) as adjuvant treatment for autologous blood transfusions ( 3 units ) in elective surgery . Four and 2 weeks before surgery , 49 patients received 6 x 10,000 U of rhEpo . delta Hb values ( days -28 and 0 ) of the rhEpo group were compared to delta Hb values of 52 controls ( no rhEpo ) . Reticulocytes were measured at days -21 , -14 , -7 and 0 . Peri- and postoperative supplementary homologous blood requirements were compared in the two r and omized groups . delta Hb of rhEpo group was 0.96 g/dl ( mean value ) and 2.38 for controls . Reticulocyte count increased earlier and to higher levels in rhEpo-treated patients . Except in 1 case , Epo was well tolerated . These results indicate that autologous predonation ( 3 x 400 ml ) does not create anemia if adjuvant Epo treatment is given . However , homologous blood requirements were not significantly different , which is probably due to the fact that 96 of the 101 treated patients underwent elective orthopedic surgery requiring limited blood replacement . Significant benefit of the Epo regimen can be expected in elective cardiovascular and hepatic surgery where larger amounts of blood ( 5 - 6 units ) are needed Total hip joint arthroplasty is frequently associated with transfusion of allogeneic blood ( 1 , 2 ) . Although serologic screening has reduced the risk for viral infection to a low level ( 3 , 4 ) , the public is highly concerned about this potential complication of transfusion ( 5 ) . Therefore , further refinement of strategies to avoid exposure to allogeneic blood is needed . The most commonly used preventive strategy is autologous blood donation ( 6 ) . Blood is collected from the patient before surgery and is reinfused if transfusion is necessary . In the past decade , this maneuver , which reduces exposure to pathogens and red cell alloimmunization , has become a st and ard of care in orthopedic surgery ( 7 , 8) . However , autologous blood donation has several disadvantages . First , donation and banking of autologous blood are inconvenient to patients ( 9 , 10 ) . Second , phlebotomy increases the prevalence of postoperative anemia and transfusion ( either autologous or allogeneic ) ( 11 ) . Third , use of autologous blood is not without risk ( 12 , 13 ) . Bacterial contamination of predonated blood ( 14 ) and major transfusion reactions ( due to administrative error ) ( 15 ) are rare but may be life-threatening . Finally and most important , many patients are not eligible for predonation because of concomitant medical conditions ( 16 ) . Erythropoietin , a glycoprotein produced by the kidney , stimulates production of red blood cells from the bone marrow ( 17 ) . Administration of recombinant human erythropoietin ( epoetin alfa ) reduces the risk for allogeneic blood transfusion in patients undergoing total hip joint arthroplasty ( 18 , 19 ) . Factors that influence the response to epoetin alfa include the dose and timing of treatment ( 20 ) , coadministration of iron ( 21 , 22 ) , and baseline hemoglobin concentration ( 23 ) . Although several different preoperative regimens have been described , the regimen approved by the U.S. Food and Drug Administration consists of four subcutaneous injections of epoetin alfa , 600 U/kg of body weight , administered before surgery ( weeks 3 , 2 , and 1 and the day of surgery ) ( 24 ) . Thus , a person weighing 70 kg would require a total dose of 168 000 U. On the basis of subgroup analysis from a previous study ( 18 ) , we hypothesized that a high dose of oral iron used in conjunction with a more prolonged epoetin alfa dosing schedule might produce a better hematologic response than that obtained with the st and ard regimen . We therefore evaluated the efficacy of two different epoetin alfa dose regimens . Methods Patients The study was a double-blind , r and omized , parallel-group , multicenter clinical trial comparing the efficacy of epoetin alfa ( Eprex , Janssen-Ortho Inc. , Toronto , Ontario , Canada ) with placebo in adult patients undergoing total hip joint arthroplasty . The trial was conducted at 13 teaching and 4 community hospitals in Canada from May 1996 to April 1999 . The protocol was approved by the institutional review board of each participating center . Eligible patients had a hemoglobin concentration of 98 to 137 g/L and did not predonate blood . At centers where an autologous blood donation program was available , blood predonation was discussed with patients ; those who participated in the study were either ineligible for predonation because of medical contraindication or declined this option . Persons with rheumatoid arthritis , recent gastrointestinal or intracranial bleeding , iron deficiency , seizures , blood dyscrasias , or uncontrolled hypertension ( diastolic blood pressure>100 mm Hg ) were excluded from the study . Patients who required revision arthroplasty or those in whom red cell salvage devices were considered essential were not enrolled . All patients gave written informed consent . Baseline and R and omization Procedures Participants were screened for eligibility 7 weeks before surgery . A history and physical examination were performed , and a complete blood count , iron studies , and blood chemistry were obtained ; patients then began oral iron therapy . Six weeks before surgery , eligible patients were r and omly assigned to one of three treatment groups . R and omization was performed according to a computer-generated schedule using a block size of 13 and an allocation ratio of 3:5:5 to the high-dose epoetin group , low-dose epoetin group , or placebo group , respectively . Treatment Regimens Patients began daily oral iron therapy at least 42 days before surgery and continued therapy until the day of hospital discharge . Three capsules per day were recommended . In patients who were intolerant of iron , the number of capsules was reduced to the point of tolerability . The iron preparation prescribed was Niferex-150 ( Schwarz Pharma , Mequon , Wisconsin ) . This polysaccharideiron complex was selected because of its good tolerability and high bioavailability of elemental iron ( 150 mg per capsule ) ( 25 ) . Patients received four weekly subcutaneous injections of placebo , high-dose epoetin alfa ( 40 000 U ) , or low-dose epoetin alfa ( 20 000 U ) starting 4 weeks before surgery . The total possible dose was 160 000 U in the high-dose group and 80 000 U in the low-dose group . The study drug was withheld if the hemoglobin concentration was 150 g/L or more , systolic blood pressure was 200 mm Hg or more , or the diastolic blood pressure was 105 mm Hg or more . During the trial , the study coordinator at the data coordinating center , who was aware of the patient 's hemoglobin concentration , authorized administration of study drug before each visit . This person had no contact with patients and did not assess outcomes . Follow-up Schedule Patients were evaluated 28 , 21 , 14 , and 7 days before surgery . At these visits , vital signs and adverse events were recorded by the visiting nurse . Patients , surgeons , and nurses were unaware of treatment assignments and laboratory results . Hemoglobin concentration on the day of surgery was available to the surgeon and other health care personnel , but the reticulocyte count and the previous hemoglobin concentration were not . Blood loss was quantified by weighing sponges and measuring suction volume intraoperatively and subtracting the volume of the irrigation fluid . Patients were seen 1 , 3 , and 5 days after surgery ; blood work was performed at these times . On the fifth day after surgery , patients underwent duplex ultrasonography ( 26 , 27 ) to evaluate both legs for the presence of deep venous thrombosis . Transfusion Policy Transfusion of allogeneic blood was performed according to the usual practice of attending surgeons and anesthesiologists . We did not establish criteria for transfusion ; however , the usual policy in Canada is not to perform transfusion in asymptomatic patients on the basis of a specific hemoglobin threshold . No patient donated or received autologous blood . Outcome Measures The primary outcome measure was occurrence of allogeneic blood transfusion . Secondary outcomes were changes in reticulocyte count and hemoglobin concentration . Adverse events were determined according to World Health Organization criteria ( 28 ) . The proportion of patients who experienced thromboembolic disease ( proximal or distal deep venous thrombosis and pulmonary embolus ) and serious adverse events was compared among the treatment groups . Statistical Analysis Before the start of the study , retrospective chart review was performed to estimate the transfusion rate in patients undergoing hip arthroplasty ( n = 471 ) who had characteristics similar to those of our patients . In those patients , the rate of allogeneic transfusion was 39 % ( 95 % CI , 34 % to 43 % ) . The reduction in the transfusion rate considered clinical ly important was 20 % . On the basis of pharmacokinetic data , the higher dose of epoetin alfa was judged likely to be more efficacious ( 29 ) than the lower dose . Therefore , we estimated that the transfusion rate would decrease from 40 % to 15 % in the high-dose group and from 40 % to 20 % in the low-dose group . In accordance with these assumptions , we used an asymmetric r and omization schedule that allocated a greater number of patients to the low-dose epoetin alfa and placebo groups ( 5 patients for every 3 that were allocated to the high-dose epoetin alfa group ) . This maneuver ensured adequate statistical power ( 80 % ) to compare the transfusion rate in the high-dose and low-dose groups with that in the placebo group . Since an allowance of 5 % was made for unevaluable patients , 83 patients per group were required in the low-dose and placebo groups and 50 patients were needed in the high-dose group . Accordingly , the total sample size requirement was 216 patients . All statistical analyses of efficacy measures were performed on an intention-to-treat basis , which was prospect ively defined to include patients who had received at least one dose of study medication and subsequently underwent surgery within 1 week of the scheduled date . Separate chi-square tests were done to compare the proportion of patients who required transfusion in the placebo group with that among patients assigned to the low-d Output:	ESAs offer an alternative blood conservation method to avoid ABT in patients undergoing hip or knee surgery
MS21833	*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 & AIMS Few data have been published on the performance of colorectal cancer ( CRC ) screens that use multiple rounds of the fecal immunochemical test ( FIT ) . We evaluated outcomes of 4 screening rounds in over 7 years in an Italian population -based program . METHODS We conducted a prospect i ve cohort study of 2959 average-risk subjects , aged 50 - 74 years , who were invited for the first screening round in 2001 . We assessed the participation rate , the yield of advanced adenomas and CRC detected in the screening examinations , and we collected information about interval CRCs , with a follow-up period of 8.5 years . RESULTS Participation in each round varied from 56 % to 63 % ; 48.1 % of eligible subjects attended all 4 invitations . The positive predictive value of the FIT for advanced neoplasia ( CRC or advanced adenoma ) was 40 % at the first round , and approximately 33 % in the subsequent rounds . This decrease was attributable mainly to a decrease in the detection of CRC , although a high rate of advanced adenomas ( range , 0.8%-1.7 % ) was observed over all rounds . To find one advanced neoplasia in the study period the number of people that needed to be screened was 28 , and the number of tests needed was 74 . CONCLUSIONS About 60 % of invited individuals participated in every single round of FIT screening for CRC , but less than 50 % attended all 4 tests . A high detection rate of advanced adenomas in all rounds indicates that FIT screening could have a higher impact on incidence of CRC than the guaiac fecal occult blood test Purpose Fecal immunochemical tests ( FITs ) have been developed to address analytical problems inherent in the older guaiac-based fecal occult blood tests ( g-FOBTs ) . Our aim was to compare the performance characteristics of one g-FOBT ( Hemoccult II ) and two FITs ( the Hemoccult ICT and MagStream HemSp ) relative to colonoscopy for the detection of colorectal cancer and significant precursor lesions . We also examined whether a 1-day collection strategy would negatively impact test diagnostic performance . Methods We used a prospect i ve observational cohort design in a Canadian population eligible for screening . All participants received colonoscopy after performing the occult blood tests . Results One thous and seventy-five individuals were enrolled ( mean age 56.3 years , 53.8 % females ) . Using colonoscopy as the gold st and ard , the sensitivity for screen-relevant neoplasm was determined for Hemoccult II ( 7.2 , 95 % CI : 1.1–13.4 ) , Hemoccult ICT ( 23.2 % : 13.2–33.1 ) , and MagStream HemSp using 67 μg/gram stool as the cut-off ( 23.2 % : 13.2–33.1 ) . The Magstream HemSp , using a cut-off threshold of 30 μg/gram stool , had the lowest specificity at 87.6 % ( 85.4–89.6 ) , while the Hemoccult II had the highest at 98.8 % ( 98.1–99.5 ) . Single-day stool testing reduced the false-positive rates of all tests without significantly reducing the sensitivity . Conclusion We found that FITs have a significantly increased sensitivity but reduced specificity for screen-relevant neoplasm compared to g-FOBT using colonoscopy as the gold st and ard . Optimal threshold levels for hemoglobin detection depend on the desired trade off between sensitivity and false-positive rate . Single-day testing with an FIT may be an option to enhance population compliance with screening 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 . ) Context Several immunochemical fecal occult blood tests ( FOBTs ) that use different antibodies against human blood components are available . Contribution This study compared characteristics of 6 qualitative immunochemical FOBTs and 1 guaiac-based FOBT to identify adenomas among adults who attended screening colonoscopy . The FOBTs had widely varying performance characteristics . Sensitivity and specificity for detecting advanced adenomas ranged from 25 % to 72 % and 70 % to 97 % , respectively , for the immunochemical tests and were 9 % and 96 % , respectively , for the guaiac test . Caution One-day stool sample s were used , and stool was frozen before testing . Implication Qualitative immunochemical FOBTs have varying performance characteristics for detecting precancerous colorectal lesions . The Editors Colorectal cancer ( CRC ) is the third most common cancer in the world ( 1 ) , with about 1 million new cases and more than 500000 deaths per year . Because most cases of CRC are sporadic and develop from removable precancerous lesions ( adenomas ) and curable early- stage cancer ( 2 ) , screening for CRC has high potential for reducing morbidity and mortality . R and omized , controlled trials have demonstrated reduced mortality with guaiac-based fecal occult blood testing ( FOBT ) followed by colonoscopy or sigmoidoscopy if the FOBT result is positive ( 3 ) . However , guaiac-based FOBT , which detects the pseudoperoxidase activity of heme or hemoglobin , has important limitations . It is not specific for human hemoglobin , and false-positive and false-negative results can result from certain compounds or medications in foods ( for example , red meat or vitamin C ) ( 4 ) that should be avoided during the days before testing . Another important limitation is the low diagnostic performance for precursors to CRC . An advantage of guaiac-based FOBT is the simple analysis , which can easily be done at the physician 's office , even though reliable interpretation of test results requires training ( 5 , 6 ) . Immunochemical FOBTs that use specific antibodies against human blood components overcome the problem of diet or medication restriction . Unlike quantitative immunochemical FOBTs , qualitative immunochemical FOBTs that mostly use immunochromatographic technology also allow simple , office-based analysis . However , there are differences among qualitative immunochemical FOBTs . For example , the antibodies used and the different detection limits may influence the diagnostic performance , especially with respect to detection of precursor lesions . We aim ed to determine and compare performance characteristics of different qualitative immunochemical FOBTs for the detection of colorectal adenomas in a large sample of women and men undergoing screening colonoscopy . Methods Study Design and Sample The analyses were part of the BliTz study ( Begleitende Evaluierung innovativer Testverfahren zur Darmkrebsfrherkennung ) , an ongoing screening study conducted in cooperation with 20 gastroenterology practice s in southwestern Germany since January 2006 that aims to comparatively evaluate new tests for early detection of CRC . The study includes participants undergoing screening colonoscopya procedure that the German health care system has offered since October 2002 to average-risk persons 55 years or older . In Germany , preliminary consultation for any type of cancer screening is mostly done by general practitioners . For screening colonoscopy , patients are referred to the gastroenterologist only when the decision to have colonoscopy is made . All participants had a preliminary consultation with a gastroenterologist to receive detailed information and advice about screening colonoscopy . They were informed about and invited to participate in the study at that time . After we received written informed consent , we asked patients scheduled for screening colonoscopy to provide a stool sample before bowel preparation . Physicians who did colonoscopy and histologic examination were blinded to FOBT results . After colonoscopy , we collected reports on colonoscopic and histologic findings and extracted information in a st and ardized manner while blinded to the results of stool testing . We did not query patients about adverse events of testing ( such as psychological distress ) . The ethics committee of the University of Heidelberg , Heidelberg , Germany , approved the study . We included patients who provided stool sample s for qualitative immunochemical FOBTs until 13 December 2007 . The Figure shows the numbers of all potentially eligible patients . Figure . Study flow diagram . FOBadv = FOB advanced ( ulti med , Ahrensburg , Germany ) ; FOBplus = Bionexia FOBplus ( DIMA , Gttingen , Germany ) ; Hb/Hp C = Bionexia Hb/Hp Complex ( DIMA ) ; HO = HemOccult ( Beckman Coulter , Krefeld , Germany ) ; immoCare = immoCARE-C ( CAREdiagnostica , Voerde , Germany ) ; PreventID CC = PreventID CC ( Preventis , Bensheim , Germany ) ; QuickVue = QuickVue iFOB ( Quidel , San Diego , California ) . * The exclusion of 44 patients overall was due to missing or noninterpretable test cards . Of 1785 patients undergoing screening colonoscopy who agreed to participate , 111 were excluded because of visible rectal bleeding or preceding positive FOBT result . We excluded 13 patients because of inflammatory bowel disease . These patients usually receive close colonoscopic surveillance and would not be regarded as the target population for primary FOBT screening . We excluded 117 patients because they had undergone colonoscopy in the past 5 years and thus would not be eligible for primary FOBT screening ( if the previous colonoscopy result was positive , they are recommended for colonoscopic surveillance ; if the result was negative , they are at very low risk for colorectal neoplasia ) . We further excluded participants whose stool sample s were collected after colonoscopy only ( and thus violated the study protocol [ n= 65 ] ) , those with inadequate bowel preparation before colonoscopy ( n= 79 ) , and those with incomplete colonoscopy ( that is , the cecum was not reached , [ n= 22 ] ) . We excluded patients who received a histologically confirmed diagnosis of CRC ( this subgroup comprised only 11 participants by the end of 2007 and would not allow meaningfully precise performance estimates for this end point ) . Sensitivity with respect to CRC will be analyzed separately after continued recruitment of a much larger number of screening participants . We excluded 10 participants with nondefined polyps ( no histologic reports were available ) because we could not definitively determine the presence or absence of advanced adenomas in this group . Finally , we excluded participants with pseudopolyps ( n= 38 ) because these patients probably have had ulcerative colitis or undocumented inflammatory bowel disease . Stool Sample Collection Participants undergoing screening colonoscopy typically present at the gastroenterology practice for preliminary consultation about 1 week before colonoscopy . At that time , eligible patients received a study package that contained 1 test card for guaiac-based FOBT ( HemOccult , Beckman Coulter , Krefeld , Germany ) , a small container ( 60 mL ) for stool collection , a collection tissue for avoiding contact of the stool with toilet water , and detailed instructions for stool collection . Stool sample s were collected at home with no specific recommendations for diet or medicine restrictions . Patients received detailed instructions for sampling : Collect 1 bowel movement by using the collection tissue ; apply stool with a spatula ( provided in the study package ) on 2 windows of 1 HemOccult test card and store the test card at room temperature ; and fill at least half of the small container with stool by using plastic spoons ( provided in the study package ) , and store a plastic bag with the container in the freezer or , if not possible , Output:	For gFOBT , we found no site-specific difference ( proximally vs distally located ) of pooled sensitivities observed in the colorectal cancer ( CRC ) , advanced adenomas , and advanced neoplasms groups . Summary receiver operating characteristic curve analyses showed similar patterns for both types of FOBT regarding the diagnostic accuracy for detecting colorectal neoplasms according to the anatomical sites of the colorectum . Conclusion iFOBT had higher sensitivity for detecting advanced adenomas and advanced neoplasia located in the distal colon/rectum than that for those in the proximal colon
MS21834	*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 Persistent pain is a challenging clinical problem after breast cancer treatment . After surgery , inflammatory pain and nociceptive input from nerve injury induce central sensitization which may play a role in the genesis of persistent pain . Using quantitative sensory testing , we tested the hypothesis that adding COX-2 inhibition to st and ard treatment reduces hyperalgesia after breast cancer surgery . A secondary hypothesis was that patients developing persistent pain would exhibit more postoperative hyperalgesia . Methods 138 women scheduled for lumpectomy/mastectomy under general anesthesia with paravertebral block were r and omized to COX-2 inhibition ( 2x40 mg parecoxib on day of surgery , thereafter 2x200 mg celecoxib/day until day five ) or placebo . Preoperatively and 1 , 5 , 15 days and 1 , 3 , 6 , 12 months postoperatively , we determined electric and pressure pain tolerance thresholds in dermatomes C6/T4/L1 and a 100 mm VAS score for pain . We calculated the sum of pain tolerance thresholds and analyzed change in these versus preoperatively using mixed models analysis with factor medication . To assess hyperalgesia in persistent pain patients we performed an additional analysis on patients reporting VAS>30 at 12 months . Results 48 COX-2 inhibition and 46 placebo patients were analyzed in a modified intention to treat analysis . Contrary to our primary hypothesis , change in the sum of tolerance thresholds in the COX-2 inhibition group was not different versus placebo . COX-2 inhibition had an effect on pain on movement at postoperative day 5 ( p<0.01 ) . Consistent with our secondary hypothesis , change in sum of pressure pain tolerance thresholds in 11 patients that developed persistent pain was negative versus patients without pain ( p<0.01 ) from day 5 to 1 year postoperatively . Conclusions Perioperative COX-2 inhibition has limited value in preventing sensitization and persistent pain after breast cancer surgery . Central sensitization may play a role in the genesis of persistent postsurgical pain Background : Regional anesthesia improves postoperative analgesia and enhances quality of recovery ( QoR ) after ambulatory surgery . This r and omized , double-blinded , parallel-group , placebo-controlled trial examines the effects of multilevel ultrasound-guided paravertebral blocks ( PVBs ) and total intravenous anesthesia on QoR after ambulatory breast tumor resection . Methods : Sixty-six women were r and omized to st and ardized general anesthesia ( control group ) or PVBs and propofol-based total intravenous anesthesia ( PVB group ) . The PVB group received T1–T5 PVBs with 5 ml of 0.5 % ropivacaine per level , whereas the control group received sham subcutaneous injections . Postoperative QoR was design ated as the primary outcome . The 29-item ambulatory QoR tool was administered in the preadmission clinic , before discharge , and on postoperative days 2 , 4 , and 7 . Secondary outcomes included block success , pain scores , intra- and postoperative morphine consumption , time to rescue analgesia , incidence of nausea and vomiting , and hospital discharge time . Results : Data from sixty-four patients were analyzed . The PVB group had higher QoR scores than control group upon discharge ( 146 vs. 131 ; P < 0.0001 ) and on postoperative day 2 ( 145 vs. 135 ; P = 0.013 ) ; improvements beyond postoperative day 2 lacked statistical significance . None of the PVB group patients required conversion to inhalation gas – based general anesthesia or experienced block-related complications . PVB group patients had improved pain scores on postanesthesia care unit admission and discharge , hospital discharge , and postoperative day 2 ; their intraoperative morphine consumption , incidence of nausea and vomiting , and discharge time were also reduced . Conclusion : Combining multilevel PVBs with total intravenous anesthesia provides reliable anesthesia , improves postoperative analgesia , enhances QoR , and expedites discharge compared with inhalational gas- and opioid-based general anesthesia for ambulatory breast tumor resection BACKGROUND : The efficacy of continuous wound infiltration with local anesthetic has not been compared with that of thoracic paravertebral block ( PVB ) after breast surgery . In this study , we evaluated the analgesic efficacy and morphine consumption of the two techniques after mastectomy . METHODS : Forty-eight patients undergoing modified radical mastectomy with axillary dissection were r and omly assigned to either a preoperative PVB with 20 mL of ropivacaine 0.5 % ( group PVB ) or a continuous ropivacaine 0.5 % infusion ( CRI ) at a 2 mL/h rate for each of two multilumen catheters placed subcutaneously at the end of the procedure ( group CRI ) . The catheters were left in place for 24 h postoperatively . A st and ardized general anesthetic was administered to all patients . Postoperative morphine consumption , pain scores and painful restricted movement of the shoulder for 24 h postoperatively as well as incidence of adverse events , including postoperative nausea and vomiting , were recorded . RESULTS : Morphine consumption was similar between groups ( PVB : 42.6 ± 11 vs CRI : 38.7 ± 11 mg in 24 h , P = 0.225 ) . Absolute pain scores were low in both groups . Four hours after surgery , group PVB showed a significant reduction in postoperative pain ( PVB : 0 [ 0–10 ] vs CRI : 0 [ 0–30 ] , P = 0.002 ) and reduced painful restricted movement ( P = 0.004 ) , whereas the CRI group had lower pain scores ( PVB : 10 [ 0–30 ] vs CRI : 0 [ 0–20 ] , P = 0.034 ) and painful restricted movement ( P = 0.043 ) 16 and 24 h ( PVB : 10 [ 0–30 ] vs CRI : 0 [ 0–30 ] , P = 0.012 ) after surgery . Postoperative nausea and vomiting was significantly more frequent in the CRI group ( P = 0.017 ) . CONCLUSIONS : Continuous wound infiltration of local anesthetics is an effective alternative to paravertebral analgesia after mastectomy with axillary dissection Background The pectoral nerves ( PECS ) block can not block the most internal mammary region , whereas a transversus thoracic muscle plane ( TTP ) block can . The combination of PECS and TTP blocks may be suitable for anterior chest surgery . We studied patients undergoing mastectomy to assess whether the combination of PECS and TTP blocks provides better analgesia than PECS block alone . Methods Seventy adult female patients undergoing unilateral mastectomy under general anaesthesia were r and omly allocated to receive either the combination of PECS and TTP blocks ( PT group , n=35 ) or the PECS block only ( C group , n=35 ) . The primary outcome measure was visual analog scale pain score . Secondary outcomes were the sensory level loss confirmed by cold tests and additional analgesic drugs within 24 h after the operation . Results The visual analog scale pain scores were lower in the PT group than the C group . The use of postoperative additional analgesic drugs was also lower lower in the PT group than that in the C group . In the majority of patients in the PT group , sensory loss was confirmed in both the anterior and the lateral branches of thoracic nerves ( Th2–6 ) . Conclusion Compared with PECS block , the combination of PECS and TTP blocks provides effective perioperative pain relief for breast cancer surgery . Clinical trial registration University Hospital Medical Information Network ( UMIN ) ID number 000018299 Avoidance of general anaesthesia for breast surgery may be because of clinical reasons or patient choice . There is emerging evidence that the use of regional anaesthesia and the avoidance of volatile anaesthetics and opioid analgesia may have beneficial effects on oncological outcomes . We conducted a prospect i ve observational case series of 16 breast cancer surgeries performed under thoracic paravertebral plus pectoral nerve block with propofol sedation to demonstrate feasibility of technique , patient acceptability and surgeon satisfaction . Fifteen out of 16 cases were successfully completed under sedation and regional anaesthesia , with one conversion to general anaesthesia . Eleven out of 16 cases required low‐dose intra‐operative opioid analgesia . Out of the 15 surgical procedures completed under regional anaesthesia with sedation , all patients experienced either no or minimal intra‐operative pain , and all would choose this anaesthetic technique again . Surgeon‐reported operating conditions were ‘ indistinguishable from general anaesthesia ’ in most cases , and surgeons were ‘ extremely satisfied ’ or ‘ satisfied ’ with the technique after every procedure . Combined thoracic paravertebral plus pectoral nerve block with intra‐operative sedation is a feasible technique for breast surgery Background and Objectives Serratus plane block is performed for analgesia of the anterior chest wall . However , there has been no study concerning the appropriate volume for this block . This prospect i ve r and omized controlled study assesses the dermatomal spread and analgesic effects of serratus plane block . Methods Ultrasound-guided serratus plane block was performed for breast cancer surgery . The patients were r and omly assigned to receive 20 or 40 mL of 0.375 % ropivacaine . The primary end point was the number of affected dermatomes as assessed by cold test and pinprick test 20 minutes after the block procedure . Secondary end points were the time until the first postoperative analgesic rescue , adverse effects , and complications . Results The number of affected dermatomes assessed by the cold test for patients receiving 40 mL of 0.375 % ropivacaine was significantly larger than that for patients receiving 20 mL ( P = 0.002 ; 6 [ 5–7 ] vs 4 [ 3–4 ] dermatomes ) . Similarly , with the pinprick test , the affected area was larger for the 40 mL group than for the 20 mL group ( P = 0.009 ; 4 [ 2–6 ] vs 2 [ 1–3 ] dermatomes ) . There were no differences between the 2 groups in secondary end points . Conclusions Ultrasound-guided serratus plane block spread in the craniocaudal direction is more widespread with 40 mL than with 20 mL of 0.375 % ropivacaine . The time until the first postoperative analgesic rescue dose was not extended by a larger volume of injection . Clinical Trials Registration UMIN Clinical Trials Registry ( identifier UMIN000016549 ) BACKGROUND Breast surgery is an exceedingly common procedure with an increased incidence of acute and chronic pain . Pectoral nerve block is a novel peripheral nerve block alternative to neuro-axial and paravertebral blocks for ambulatory breast surgeries . OBJECTIVES This study aims to compare the analgesic efficacy and safety of modified Pecs block with ketamine plus bupivacaine versus bupivacaine in patients undergoing breast cancer surgery . STUDY DESIGN A r and omized , double-blind , prospect i ve study . SETTING Academic medical center . METHODS This study is registered at www . clinical trials.gov under number : ( NCT02620371 ) after approval by the ethics committee of South Egypt Cancer Institute , Assuit University , Assuit , Egypt . Sixty patients aged 18 - 60 years scheduled for modified radical mastectomy were enrolled and r and omly assigned into 2 groups ( 30 patients each ) : Control group patients were given ultrasound-guided , Pecs block with 30 mL of 0.25 % bupivacaine only . Ketamine group patients were given ultrasound-guided , Pecs block with 30 mL of 0.25 % bupivacaine plus ketamine hydrochloride ( 1 mg/kg ) . Patients were followed up for 48 hours postoperatively for vital signs , VAS score , first request of rescue analgesia and total morphine consumption , sedation score , and side effects . RESULTS Ketamine plus bupivacaine in Pecs block compared to bupivacaine alone prolonged the mean time of first request of analgesia ( 18.25 ± 1.98 ) , ( 12.56 ± 2.64 ) , respectively ( P < 0.001 ) , reduced total morphine consumption ( 12.50 ± 4.63 ) , ( 18.86 ± 6.28 ) , respectively ( P = 0.016 ) . With no significant difference in hemodynamics , respiratory rate , oxygen saturation , VAS and sedation scores , and side effects observed between the 2 groups ( P > 0.05 ) . LIMITATIONS This study is limited by its sample size . CONCLUSION The addition of ketamine to modified Pecs block prolonged the time to first request of analgesia and reduced total opioid consumption without serious side effects in patients who underwent a modified radical mastectomy . KEY WORDS Ketamine , bupivacaine , pecs block , postoperative , pain , breast cancer Background and Objectives General anesthesia for breast surgery may be supplemented by using a regional anesthetic technique . We evaluated the efficacy of the first pectoral nerve block ( Pecs I Output:	Quantitative analysis suggests that dexamethasone and gabapentin reduced postoperative pain . The use of paravertebral blocks also reduced postoperative pain scores , analgesia consumption and the incidence of postoperative nausea and vomiting . Intra-operative opioid requirements were documented to be lower when a pectoral nerves block was performed , which also reduced postoperative pain scores and opioid consumption .
MS21835	*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 efficacy and safety of alpha-lipoic acid given intravenously , followed by oral treatment in type 2 diabetic patients with symptomatic polyneuropathy . RESEARCH DESIGN AND METHODS In a multicenter r and omized double-blind placebo-controlled trial ( Alpha-Lipoic Acid in Diabetic Neuropathy [ ALADIN ] III Study ) , 509 out patients were r and omly assigned to sequential treatment with 600 mg alpha-lipoic acid once daily intravenously for 3 weeks , followed by 600 mg alpha-lipoic acid three times a day orally for 6 months ( A-A ; n = 167 ) ; 600 mg alpha-lipoic acid once daily intravenously for 3 weeks , followed by placebo three times a day orally for 6 months ( A-P ; n = 174 ) ; and placebo once daily intravenously for 3 weeks , followed by placebo three times a day orally for 6 months ( P-P ; n = 168 ) . Outcome measures included the Total Symptom Score ( TSS ) for neuropathic symptoms ( pain , burning , paresthesias , and numbness ) in the feet , and the Neuropathy Impairment Score ( NIS ) . Data analysis was based on the intention to treat . RESULTS No significant differences between the groups were noted for the demographic variables and the nerve function parameters at baseline . The TSS in the feet decreased from baseline to day 19 ( median [ range ] ) by -3.7 ( -12.6 to 5.0 ) points in the group given alpha-lipoic acid intravenously and by -3.0 ( -12.3 to 8.0 ) points in the placebo group ( P = 0.447 ) , but the area under curve on a daily basis was significantly smaller in the active as compared with the placebo group ( 85.6 [ 0 - 219 ] vs. 95.9 [ 5.5 - 220 ] ) ; P = 0.033 ) . After 7 months , the changes in the TSS from baseline were not significantly different between the three groups studied , which could be due to increasing intercenter variability in the TSS during the trial . The NIS decreased after 19 days by -4.34+/-0.35 points ( mean + /- SEM ) in A-A and A-P and -3.49+/-0.58 points in P-P ( P = 0.02 for alpha-lipoic acid versus placebo ) and after 7 months by -5.82+/-0.73 points in A-A , -5.76+/-0.69 points in A-P , and -4.37+/-0.83 points in P-P ( P = 0.09 for A-A vs. P-P ) . The rates of adverse events were not different between the groups throughout the study . CONCLUSIONS These findings indicate that a 3-week intravenous treatment with alpha-lipoic acid , followed by a 6-month oral treatment , had no effect on neuropathic symptoms distinguishable from placebo to a clinical ly meaningful degree , possibly due to increasing intercenter variability in symptom scoring during the study . However , this treatment was associated with a favorable effect on neuropathic deficits without causing significant adverse reactions . Long-term trials that focus on neuropathic deficits rather than symptoms as the primary criterion of efficacy are needed to see whether oral treatment with alpha-lipoic acid over several years may slow or reverse the progression of diabetic neuropathy BACKGROUND QR-333 , a topical compound that contains quercetin , a flavonoid with aldose reductase inhibitor effects , ascorbyl palmitate , and vitamin D(3 ) , was formulated to decrease the oxidative stress that contributes to peripheral diabetic neuropathy and thus alleviate its symptoms . This proof-of-principle study assessed the efficacy and safety of QR-333 against placebo in a small cohort of patients with diabetic neuropathy . METHODS This r and omized , placebo-controlled , double-blind trial included 34 men and women ( 21 - 71 years of age ) with Type 1 or 2 diabetes and diabetic neuropathy who applied QR-333 or placebo ( 2:1 ratio ) , three times daily for 4 weeks , to each foot where symptoms were experienced . Five-point scales were used to determine changes from baseline to endpoint in symptoms and quality of life ( efficacy ) . Safety was assessed through concomitant medications , adverse events , laboratory evaluations , and physical examinations . RESULTS QR-333 reduced the severity of numbness , jolting pain , and irritation from baseline values . Improvements were also seen in overall and specific quality -of-life measures . QR-333 was well tolerated . Eleven patients in the QR-333 group reported 23 adverse events ( all mild or moderate ) ; 4 in the placebo group reported 5 events ( all moderate ) . One patient who applied QR-333 noted a pricking sensation twice , the only adverse event considered possibly related to study treatment . CONCLUSIONS From this preliminary safety study , it appears that QR-333 may safely offer relief of symptoms of diabetic neuropathy and improve quality of life . These findings warrant further investigation of this topical compound Objective . To evaluate the effects of ezetimibe/simvastatin ( EZE/SIMV ) and rosuvastatin ( ROSUV ) on oxidative stress ( OS ) markers in patients with diabetic polyneuropathy ( DPN ) . Methods . We performed a r and omized , double-blind , placebo-controlled phase III clinical trial in adult patients with Type 2 Diabetes Mellitus ( T2DM ) and DPN , as evaluated by composite scores and nerve conduction studies ( NCS ) . Seventy-four subjects with T2DM were allocated 1 : 1 : 1 to placebo , EZE/SIMV 10/20 mg , or ROSUV 20 mg for 16 weeks . All patients were assessed before and after treatment : primary outcomes were lipid peroxidation ( LPO ) , and nitric oxide ( NO ) surrogate levels in plasma ; secondary outcomes included NCS , neuropathic symptom scores , and metabolic parameters . Data were expressed as mean ± SD or SEM , frequencies , and percentages ; we used nonparametric analysis . Results . LPO levels were reduced in both statin arms after 16 weeks of treatment ( p < 0.05 versus baseline ) , without changes in the placebo group . NO levels were not significantly affected by statin treatment , although a trend towards significance concerning increased NO levels was noted in both statin arms . No significant changes were observed for the NCS or composite scores . Discussion . EZE/SIMV and ROSUV are superior to placebo in reducing LPO in subjects with T2DM suffering from polyneuropathy . This trial is registered with NCT02129231 Antiretroviral toxic neuropathy causes morbidity in human immunodeficiency virus ( HIV ) patients under dideoxynucleoside therapy , benefits only partially from medical therapy , and often leads to drug discontinuation . Proposed pathogeneses include a disorder of mitochondrial oxidative metabolism , eventually related to a reduction of mitochondrial DNA content , and interference with nerve growth factor activity . Carnitine is a substrate of energy production reactions in mitochondria and is involved in many anabolic reactions . Acetyl carnitine treatment promotes peripheral nerve regeneration and has neuroprotective properties and a direct analgesic role related to glutamatergic and cholinergic modulation . The aim of this study was to evaluate acetyl-l-carnitine in the treatment of painful antiretroviral toxic neuropathy in HIV patients . Twenty subjects affected by painful antiretroviral toxic neuropathy were treated with oral acetyl-l-carnitine at a dose of 2,000 mg/day for a 4-week period . Efficacy was evaluated by means of the modified Short Form McGill Pain Question naire with each item rated on an 11-point intensity scale at weekly intervals and by electromyography at baseline and final visit . Mean pain intensity score was significantly reduced during the study , changing from 7.35 + /- 1.98 ( mean + /- SD ) at baseline to 5.80 + /- 2.63 at week 4 ( p = 0.0001 ) . Electrophysiological parameters did not significantly change between baseline and week 4 . In this study , acetyl-l-carnitine was effective and well tolerated in symptomatic treatment of painful neuropathy associated with antiretroviral toxicity . On the contrary , no effect was noted on neurophysiological parameters BACKGROUND The majority of patients receiving the platinum-based chemotherapy drug oxaliplatin develop peripheral neurotoxicity . Because this neurotoxicity involves ROS production , we investigated the efficacy of mangafodipir , a molecule that has antioxidant properties and is approved for use as an MRI contrast enhancer . METHODS The effects of mangafodipir were examined in mice following treatment with oxaliplatin . Neurotoxicity , axon myelination , and advanced oxidized protein products ( AOPPs ) were monitored . In addition , we enrolled 23 cancer patients with grade ≥ 2 oxaliplatin-induced neuropathy in a phase II study , with 22 patients receiving i.v . mangafodipir following oxaliplatin . Neuropathic effects were monitored for up to 8 cycles of oxaliplatin and mangafodipir . RESULTS Mangafodipir prevented motor and sensory dysfunction and demyelinating lesion formation . In mice , serum AOPPs decreased after 4 weeks of mangafodipir treatment . In 77 % of patients treated with oxaliplatin and mangafodipir , neuropathy improved or stabilized after 4 cycles . After 8 cycles , neurotoxicity was down grade d to grade ≥ 2 in 6 of 7 patients . Prior to enrollment , patients received an average of 880 ± 239 mg/m2 oxaliplatin . Patients treated with mangafodipir tolerated an additional dose of 458 ± 207 mg/m2 oxaliplatin despite preexisting neuropathy . Mangafodipir responders managed a cumulative dose of 1,426 ± 204 mg/m2 oxaliplatin . Serum AOPPs were lower in responders compared with those in nonresponders . CONCLUSION Our study suggests that mangafodipir can prevent and /or relieve oxaliplatin-induced neuropathy in cancer patients . Trial registration . Clinical trials.gov NCT00727922 . Funding . Université Paris Descartes , Ministère de la Recherche et de l'Enseignement Supérieur , and Assistance Publique-Hôpitaux de Paris Abstract Background and Objective : The management of diabetic neuropathy is still a challenge for physicians . The aim of this study was to assess the efficacy of a new combination of alpha lipoic acid and superoxide dismutase for the treatment of diabetic neuropathy . p ] Methods : The setting of this study was ambulatory ( outpatient ) care . A prospect i ve , non-r and omized , open-label study was conducted in 50 patients with diabetes mellitus and with a deficit in both motor and sensory nerve conduction . Treatment was with a new combination of alpha lipoic acid and superoxide dismutase ( ALA600SOD ® ) for 4 months . Electroneurographic parameters and perceived pain were assessed at baseline and after treatment . Results : After 4 months of treatment , patients significantly ( p < 0.001 ) improved their electroneurographic parameters and their perception of pain . Best improvements were observed in sensory nerve conduction . Conclusion : The combination of two powerful antioxidant agents leads to improvement in both subjective and objective parameters in patients with diabetic neuropathy . New profitable directions for investigations are opened for a non-invasive treatment of diabetic neuropathy in the future Vascular dysfunction , including impaired perfusion has a pivotal role in the pathogenesis of microvascular complications in diabetes mellitus . Both pentoxifylline ( PF ) and pentosan polysulphate ( PPS ) are known to improve microcirculation . Antioxidant and antiproteinuric effects of PF are also known . In a placebo-controlled study , we determined the possible efficacy of PF-PPS combination therapy on diabetic neuropathy and nephropathy in type 2 diabetic patients . Patients in Verum group ( n = 77 ) received PF-PPS infusions ( 100–100 mg/day ) for 5 days . Control diabetics ( Placebo group ; n = 12 ) were given only saline infusions . Specialized cardiovascular autonomic reflex tests , vibration threshold values and urinary albumin excretion were assessed before and after therapy . In Verum group , autonomic score , indicating the severity of cardiac autonomic dysfunction , decreased after therapy ( p ≤ 0.001 ) . Of the reflexes , deep breath and h and grip tests also improved after therapy ( p ≤ 0.001 ) . Vibration threshold values , an indicator of the loss of sensory nerve function , were increased after therapy ( p ≤ 0.001 ) . Results of cardiac autonomic tests and vibration threshold values remained unaltered in Placebo group . Majority of patients had normalbuminuria , which was not affected by PF-PPS . In Output:	Peripheral neuropathy is associated with an increase of reactive oxygen species and a decrease in endogenous antioxidants . Genetic predisposition to oxidative damage may be a factor . Antioxidant treatment is promising regarding treatment . Though further research is necessary to better underst and the underlying mechanism , it is evident that oxidative stress is implicated in the pathogenesis of – or is at least systematic ally present in – PN
MS21836	*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 Background Long-term hormone therapy has been the st and ard of care for advanced prostate cancer since the 1940s . STAMPEDE is a r and omised controlled trial using a multiarm , multistage platform design . It recruits men with high-risk , locally advanced , metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy . We report primary survival results for three research comparisons testing the addition of zoledronic acid , docetaxel , or their combination to st and ard of care versus st and ard of care alone . Methods St and ard of care was hormone therapy for at least 2 years ; radiotherapy was encouraged for men with N0M0 disease to November , 2011 , then m and ated ; radiotherapy was optional for men with node-positive non-metastatic ( N+M0 ) disease . Stratified r and omisation ( via minimisation ) allocated men 2:1:1:1 to st and ard of care only ( SOC-only ; control ) , st and ard of care plus zoledronic acid ( SOC + ZA ) , st and ard of care plus docetaxel ( SOC + Doc ) , or st and ard of care with both zoledronic acid and docetaxel ( SOC + ZA + Doc ) . Zoledronic acid ( 4 mg ) was given for six 3-weekly cycles , then 4-weekly until 2 years , and docetaxel ( 75 mg/m2 ) for six 3-weekly cycles with prednisolone 10 mg daily . There was no blinding to treatment allocation . The primary outcome measure was overall survival . Pairwise comparisons of research versus control had 90 % power at 2·5 % one-sided α for hazard ratio ( HR ) 0·75 , requiring roughly 400 control arm deaths . Statistical analyses were undertaken with st and ard log-rank-type methods for time-to-event data , with hazard ratios ( HRs ) and 95 % CIs derived from adjusted Cox models . This trial is registered at Clinical Trials.gov ( NCT00268476 ) and ControlledTrials.com ( IS RCT N78818544 ) . Findings 2962 men were r and omly assigned to four groups between Oct 5 , 2005 , and March 31 , 2013 . Median age was 65 years ( IQR 60–71 ) . 1817 ( 61 % ) men had M+ disease , 448 ( 15 % ) had N+/X M0 , and 697 ( 24 % ) had N0M0 . 165 ( 6 % ) men were previously treated with local therapy , and median prostate-specific antigen was 65 ng/mL ( IQR 23–184 ) . Median follow-up was 43 months ( IQR 30–60 ) . There were 415 deaths in the control group ( 347 [ 84 % ] prostate cancer ) . Median overall survival was 71 months ( IQR 32 to not reached ) for SOC-only , not reached ( 32 to not reached ) for SOC + ZA ( HR 0·94 , 95 % CI 0·79–1·11 ; p=0·450 ) , 81 months ( 41 to not reached ) for SOC + Doc ( 0·78 , 0·66–0·93 ; p=0·006 ) , and 76 months ( 39 to not reached ) for SOC + ZA + Doc ( 0·82 , 0·69–0·97 ; p=0·022 ) . There was no evidence of heterogeneity in treatment effect ( for any of the treatments ) across prespecified subsets . Grade 3–5 adverse events were reported for 399 ( 32 % ) patients receiving SOC , 197 ( 32 % ) receiving SOC + ZA , 288 ( 52 % ) receiving SOC + Doc , and 269 ( 52 % ) receiving SOC + ZA + Doc . Interpretation Zoledronic acid showed no evidence of survival improvement and should not be part of st and ard of care for this population . Docetaxel chemotherapy , given at the time of long-term hormone therapy initiation , showed evidence of improved survival accompanied by an increase in adverse events . Docetaxel treatment should become part of st and ard of care for adequately fit men commencing long-term hormone therapy . Funding Cancer Research UK , Medical Research Council , Novartis , Sanofi-Aventis , Pfizer , Janssen , Astellas , NIHR Clinical Research Network , Swiss Group for Clinical Cancer Research Background Abiraterone acetate plus prednisolone improves survival in men with relapsed prostate cancer . We assessed the effect of this combination in men starting long‐term and rogen‐deprivation therapy ( ADT ) , using a multigroup , multistage trial design . Methods We r and omly assigned patients in a 1:1 ratio to receive ADT alone or ADT plus abiraterone acetate ( 1000 mg daily ) and prednisolone ( 5 mg daily ) ( combination therapy ) . Local radiotherapy was m and ated for patients with node‐negative , nonmetastatic disease and encouraged for those with positive nodes . For patients with nonmetastatic disease with no radiotherapy planned and for patients with metastatic disease , treatment continued until radiologic , clinical , or prostate‐specific antigen ( PSA ) progression ; otherwise , treatment was to continue for 2 years or until any type of progression , whichever came first . The primary outcome measure was overall survival . The intermediate primary outcome was failure‐free survival ( treatment failure was defined as radiologic , clinical , or PSA progression or death from prostate cancer ) . Results A total of 1917 patients underwent r and omization from November 2011 through January 2014 . The median age was 67 years , and the median PSA level was 53 ng per milliliter . A total of 52 % of the patients had metastatic disease , 20 % had node‐positive or node‐indeterminate nonmetastatic disease , and 28 % had node‐negative , nonmetastatic disease ; 95 % had newly diagnosed disease . The median follow‐up was 40 months . There were 184 deaths in the combination group as compared with 262 in the ADT‐alone group ( hazard ratio , 0.63 ; 95 % confidence interval [ CI ] , 0.52 to 0.76 ; P<0.001 ) ; the hazard ratio was 0.75 in patients with nonmetastatic disease and 0.61 in those with metastatic disease . There were 248 treatment‐failure events in the combination group as compared with 535 in the ADT‐alone group ( hazard ratio , 0.29 ; 95 % CI , 0.25 to 0.34 ; P<0.001 ) ; the hazard ratio was 0.21 in patients with nonmetastatic disease and 0.31 in those with metastatic disease . Grade 3 to 5 adverse events occurred in 47 % of the patients in the combination group ( with nine grade 5 events ) and in 33 % of the patients in the ADT‐alone group ( with three grade 5 events ) . Conclusions Among men with locally advanced or metastatic prostate cancer , ADT plus abiraterone and prednisolone was associated with significantly higher rates of overall and failure‐free survival than ADT alone . ( Funded by Cancer Research U.K. and others ; STAMPEDE Clinical Trials.gov number , NCT00268476 , and Current Controlled Trials number , IS RCT N78818544 . Output:	Olaparib has been the first agent showing a benefit in terms of rPFS and ORR alone or in combination with abiraterone plus prednisone in patients with DDR deficiency prostate cancer .
MS21837	*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 examine the longitudinal association between age and intraocular pressure ( IOP ) in a large sample of Korean men and women . METHODS We conducted a prospect i ve cohort study of 274,064 young and middle-aged Korean adults with normal fundoscopic findings , following them from January 1 , 2002 , to February 28 , 2010 . Health exams were scheduled annually or biennially . At each visit , IOP was measured in both eyes using automated noncontact tonometers . The longitudinal change in IOP with age was evaluated using three-level mixed models for longitudinal paired-eye data , accounting for correlations between paired eyes and repeated measurements over time . RESULTS In fully adjusted models , the average longitudinal change in IOP per 1-year increase in age was -0.065 mm Hg ( 95 % confidence interval [ CI ] -0.068 to -0.063 ) , with marked sex differences ( P < 0.001 ) . In men , the average annual IOP change was -0.093 mm Hg ( 95 % CI -0.096 to -0.091 ) throughout follow-up . In women , the average annual IOP change was -0.006 mm Hg ( 95 % CI -0.010 to -0.003 ) , with a relatively flat association in the age range of 30 to 59 years and more marked annual decreases at younger and older ages . CONCLUSIONS Intraocular pressure was inversely associated with age in a large cohort of Korean adults attending health-screening visits . For men , this inverse association was observed throughout the entire age range , while for women it was evident only in younger ( < 30 years of age ) and older ( ≥60 years of age ) women , with no association in women aged 30 to 59 . Further research is needed to better underst and the underlying mechanisms and to reconsider cutoffs for defining high IOP by age and sex groups in Asian population OBJECTIVE To vali date an FFQ for the assessment of dietary EPA and DHA against their relative concentrations in red blood cells ( RBC ) . DESIGN Cross-sectional analysis of baseline data . Intakes of marine food products and EPA and DHA were estimated by FFQ on the basis of consumption of marine food products in the last month . Fatty acid composition of RBC membranes was quantified by GC . SETTING Saint-François d'Assise Hospital , Québec , Canada . SUBJECTS A total of sixty-five middle-aged women who participated in a r and omized clinical trial . RESULTS Spearman 's correlation coefficient between intake of EPA , DHA and EPA + DHA and their corresponding concentration in RBC was 0.46 , 0.40 and 0.42 , respectively ( all P < 0.05 ) . Multiple regression analysis of EPA+DHA intake and RBC EPA + DHA concentration indicated positive and significant correlations for oily fish ( beta = 0.44 , 95 % CI 0.16 , 0.72 , P = 0.0027 ) , total fish ( beta = 0.42 , 95 % CI 0.19 , 0.64 , P = 0.0005 ) and marine food products ( beta = 0.42 , 95 % CI 0.20 , 0.64 , P = 0.0003 ) . No other marine food products significantly predicted RBC EPA + DHA concentration . CONCLUSIONS Although the present validation study was undertaken among middle-aged women with low consumption of marine food products ( <3 servings/week ) , our FFQ provided estimates of EPA and DHA intakes that correlated fairly well with their RBC concentrations . However , the absence of correlations between EPA + DHA intakes from different marine species suggests that a minimum EPA + DHA intake is necessary to observe a relationship with RBC EPA + DHA concentrations OBJECTIVE To determine whether heart function in childhood is affected by exposure to methylmercury ( MeHg ) from seafood . STUDY DESIGN Prospect i ve study of a Faroese birth cohort ( N=1022 ) . Examinations at ages 7 and 14 years included blood pressure , heart rate variability ( HRV ) and its frequency components of autonomic origin , and brainstem auditory evoked potentials ( BAEPs ) . Mercury concentrations were determined in cord blood and in the child 's hair . RESULTS Both low-frequency ( LF ) and high-frequency ( HF ) activities decreased by about 25 % from 7 to 14 years ; they correlated well with the blood pressures . A doubling of prenatal MeHg exposure was associated with a decrease in LF and HF powers of about 6.7 % ( P=.04 ) and in the coefficient of variation of the electrocardiographic R-R interval of 2.7 % ( P=.04 ) at age 14 years . No discernible effect on blood pressure was apparent . Decreased LF variability was associated with increased latency of BAEP peak III , but adjustment for MeHg exposure substantially attenuated this correlation . CONCLUSIONS Methylmercury exposure was associated with decreased sympathetic ( LF ) and parasympathetic ( HF ) modulation of the HRV . Parallel MeHg-related delays of BAEP latencies may be caused by underlying MeHg neurotoxicity to brainstem nuclei Output:	The association of prenatal mercury exposure with lower high-frequency b and scores ( thought to reflect parasympathetic activity ) in several studies , in particular the inverse association of cord blood mercury levels with the coefficient of variation of the R-R intervals and with low-frequency and high-frequency b and s at 14 years of age in the Faroe Isl and s birth cohort study , suggests that early mercury exposure could have a long-lasting effect on cardiac parasympathetic activity .
MS21838	*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 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 Hypertension is more prevalent and clinical ly severe among African – Americans than whites . Several health behaviors influence blood pressure ( BP ) control , but effective , accessible , culturally sensitive interventions that target multiple behaviors are lacking . Purpose We evaluated a culturally adapted , automated telephone system to help hypertensive , urban African – American adults improve their adherence to their antihypertensive medication regimen and to evidence -based guidelines for dietary behavior and physical activity . Methods We r and omized 337 hypertensive primary care patients to an 8-month automated , multi-behavior intervention or to an education-only control . Medication adherence , diet , physical activity , and BP were assessed at baseline and every 4 months for 1 year . Data were analyzed using longitudinal modeling . Results The intervention was associated with improvements in a measure of overall diet quality ( + 3.5 points , p < 0.03 ) and in energy expenditure ( + 80 kcal/day , p < 0.03 ) . A decrease in systolic BP between groups was not statistically significant ( −2.3 mmHg , p = 0.25 ) . Conclusions Given their convenience , scalability , and ability to deliver tailored messages , automated telecommunications systems can promote self-management of diet and energy balance in urban African – Americans CONTEXT Poor medication adherence diminishes the health benefits of pharmacotherapies . Elderly patients with coronary risk factors frequently require treatment with multiple medications , placing them at increased risk for nonadherence . OBJECTIVE To test the efficacy of a comprehensive pharmacy care program to improve medication adherence and its associated effects on blood pressure ( BP ) and low-density lipoprotein cholesterol ( LDL-C ) . DESIGN , SETTING , AND PATIENTS A multiphase , prospect i ve study with an observational phase and a r and omized controlled trial conducted at the Walter Reed Army Medical Center of 200 community-based patients aged 65 years or older taking at least 4 chronic medications . The study was conducted from June 2004 to August 2006 . INTERVENTION After a 2-month run-in phase ( measurement of baseline adherence , BP , and LDL-C ) , patients entered a 6-month intervention phase ( st and ardized medication education , regular follow-up by pharmacists , and medications dispensed in time-specific packs ) . Following the intervention phase , patients were r and omized to continued pharmacy care vs usual care for an additional 6 months . MAIN OUTCOME MEASURES Primary end point of the observation phase was change in the proportion of pills taken vs baseline ; secondary end points were the associated changes in BP and LDL-C. Primary end point of the r and omization phase was the between-group comparison of medication persistence . RESULTS A total of 200 elderly patients ( 77.1 % men ; mean [ SD ] age , 78 [ 8.3 ] years ) , taking a mean ( SD ) of 9 ( 3 ) chronic medications were enrolled . Coronary risk factors included drug-treated hypertension in 184 patients ( 91.5 % ) and drug-treated hyperlipidemia in 162 ( 80.6 % ) . Mean ( SD ) baseline medication adherence was 61.2 % ( 13.5 % ) . After 6 months of intervention , medication adherence increased to 96.9 % ( 5.2 % ; P<.001 ) and was associated with significant improvements in systolic BP ( 133.2 [ 14.9 ] to 129.9 [ 16.0 ] mm Hg ; P = .02 ) and LDL-C ( 91.7 [ 26.1 ] to 86.8 [ 23.4 ] mg/dL ; P = .001 ) . Six months after r and omization , the persistence of medication adherence decreased to 69.1 % ( 16.4 % ) among those patients assigned to usual care , whereas it was sustained at 95.5 % ( 7.7 % ) in pharmacy care ( P<.001 ) . This was associated with significant reductions in systolic BP in the pharmacy care group ( -6.9 mm Hg ; 95 % CI , -10.7 to -3.1 mm Hg ) vs the usual care group ( -1.0 mm Hg ; 95 % CI , -5.9 to 3.9 mm Hg ; P = .04 ) , but no significant between-group differences in LDL-C levels or reductions . CONCLUSIONS A pharmacy care program led to increases in medication adherence , medication persistence , and clinical ly meaningful reductions in BP , whereas discontinuation of the program was associated with decreased medication adherence and persistence . TRIAL REGISTRATION clinical trials.gov Identifier : 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 This study evaluated the effectiveness of a skills training program design ed to teach disease management to Latinos with schizophrenia treated at a community mental health center . Ninety-two Latino out patients with schizophrenia and their design ated relatives were r and omly assigned to 3 months of skills training ( ST ) versus customary outpatient care ( CC ) and followed for a total of 9 months . The skills training approach was culturally adapted mainly by including the active participation of key relatives to facilitate acquisition and generalization of disease management skills into the patients ' natural environment . There was a significant advantage for the ST group over the CC group on several symptom measures , skill acquisition and generalization , level of functioning , and rates of rehospitalization . There were no significant differences between the groups on quality of life or caregiver burden . Skills training had a direct effect on skill acquisition and generalization , and utilization of disease management skills led to decreased rates of rehospitalization . Incorporating an intensive , culturally relevant generalization effort into skills training for Latinos with schizophrenia appeared to be effective in teaching disease management and viable in a community mental health center OBJECTIVE to develop and assess the feasibility of a motivational interviewing ( MI ) based asthma self-management program for inner-city , African-American , adolescents with asthma . METHODS 37 African-American adolescents ( age 10 - 15 years ) recently seen in an inner-city emergency department for asthma and prescribed an asthma controller medication participated in the newly developed program consisting of 5 home visits . Adolescents and their caregivers completed phone-based surveys before and after the intervention . RESULTS 95 % of the adolescents completed all 5 sessions ; 89 % of caregivers and 76 % of adolescents believed other families would benefit from the intervention . Caregivers were more likely to report 100 % adherence post-intervention compared to pre-intervention and reported a trend for adolescents taking greater responsibility for their asthma . There were no pre-post-differences in adolescent-reported medication adherence , but adolescents did reported increased motivation and readiness to adhere to treatment . Caregivers and adolescents each reported statistically significant increases in their asthma quality of life . CONCLUSIONS the findings from this pilot study suggest that MI is a feasible and promising approach for increasing medication adherence among inner-city adolescents with asthma and is worthy of further evaluation in a r and omized trial . PRACTICE IMPLICATION S incorporating MI into disease management programs may enhance their effectiveness 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 This paper reports the initial results of a pilot study to evaluate the acceptability and effectiveness of a program to enhance health literacy in low-income HIV-infected Latino men and women receiving antiretroviral therapy . Participants rated the program highly on measures of satisfaction , providing evidence of its acceptability . The effectiveness of the program was assessed in comparisons of the intervention ( n = 41 ) and st and ard care only ( n = 40 ) groups at baseline and 6-week intervals . Program participants showed significant improvement over comparison group participants on measures of HIV/AIDS and treatment-related knowledge and recognition and underst and ing of HIV terms . Although there were no significant changes in adherence mastery and behaviors during the 6-week follow up period , there were significant changes in program participants ' knowledge about medication adherence . Future steps to examine the sustainability of the program in the medical management of patients are planned in addition to determining its long-range relative impact 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 Output:	There was a lack of congruence among studies in the way adherence was measured and reported . No single intervention has been seen to be universally successful , particularly for patients from ethnic minority background
MS21839	*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 Austrian Breast and Colorectal Cancer Study Group trial-12 ( ABCSG-12 ) bone sub study assesses zoledronic acid for preventing bone loss associated with adjuvant endocrine therapy and reports on long-term findings of bone-mineral density ( BMD ) during 3 years of treatment and 2 years after completing adjuvant treatment with or without zoledronic acid . The aim of this sub study is to gain insight into bone health in this setting . METHODS ABCSG-12 is a r and omised , open-label , phase III , 4-arm trial comparing tamoxifen ( 20 mg/day orally ) and goserelin ( 3.6 mg subcutaneously every 28 days ) versus anastrozole ( 1 mg/day orally ) and goserelin ( 3.6 mg subcutaneously every 28 days ) , both with or without zoledronic acid ( 4 mg intravenously every 6 months ) for 3 years in premenopausal women with endocrine-responsive breast cancer . This prospect i ve bone sub protocol measured BMD at 0 , 6 , 12 , 36 , and 60 months . The primary endpoint of the bone sub study ( secondary endpoint in the main trial ) was change in BMD at 12 months , assessed by dual-energy X-ray absorptiometry in assessable patients . Analyses were intention to treat . Statistical significance was assessed by t tests . The ABCSG-12 trial is registered on the Clinical Trials.gov website , number NCT00295646 . FINDINGS 404 patients were prospect ively included in the bone sub study and r and omly assigned to endocrine therapy alone ( goserelin and anastrozole or goserelin and tamoxifen ; n=199 ) or endocrine therapy concurrent with zoledronic acid ( goserelin , anastrozole , and zoledronic acid or goserelin , tamoxifen , and zoledronic acid ; n=205 ) . After 3 years of treatment , endocrine therapy alone caused significant loss of BMD at the lumbar spine ( -11.3 % , mean difference -0.119 g/cm(2 ) [ 95 % CI -0.146 to -0.091 ] , p<0.0001 ) and trochanter ( -7.3 % , mean difference -0.053 g/cm(2 ) [ -0.076 to -0.030 ] , p<0.0001 ) . In patients who did not receive zoledronic acid , anastrozole caused greater BMD loss than tamoxifen at 36 months at the lumbar spine ( -13.6 % , mean difference -0.141 g/cm(2 ) [ -0.179 to -0.102 ] vs -9.0 % , mean difference -0.095 g/cm(2 ) [ -0.134 to -0.057 ] , p<0.0001 for both ) . 2 years after the completion of treatment ( median follow-up 60 months [ range 15.5 - 96.6 ] ) , patients not receiving zoledronic acid still had decreased BMD at both sites compared with baseline ( lumbar spine -6.3 % , mean difference -0.067 g/cm(2 ) [ -0.106 to -0.027 ] , p=0.001 ; trochanter -4.1 % , mean difference -0.03 g/cm(2 ) [ -0.062 to 0.001 ] , p=0.058 ) . Patients who received zoledronic acid had stable BMD at 36 months ( lumbar spine + 0.4 % , mean difference 0.004 g/cm(2 ) [ -0.024 to 0.032 ] ; trochanter + 0.8 % , mean difference 0.006 g/cm(2 ) [ -0.018 to 0.028 ] ) and increased BMD at 60 months at both sites ( lumbar spine + 4.0 % , mean difference 0.039 g/cm(2 ) [ 0.005 - 0.075 ] , p=0.02 ; trochanter + 3.9 % , mean difference 0.028 g/cm(2 ) [ 0.003 - 0.058 ] , p=0.07 ) compared with baseline . INTERPRETATION Goserelin plus tamoxifen or anastrozole for 3 years without concomitant zoledronic acid caused significant bone loss . Although there was partial recovery 2 years after completing treatment , patients receiving endocrine therapy alone did not recover their baseline BMD levels . Concomitant zoledronic acid prevented bone loss during therapy and improved BMD at 5 years BACKGROUND Aromatase inhibitors effectively prevent breast cancer recurrence and development of new contralateral tumours in postmenopausal women . We assessed the efficacy and safety of the aromatase inhibitor anastrozole for prevention of breast cancer in postmenopausal women who are at high risk of the disease . METHODS Between Feb 2 , 2003 , and Jan 31 , 2012 , we recruited postmenopausal women aged 40 - 70 years from 18 countries into an international , double-blind , r and omised placebo-controlled trial . To be eligible , women had to be at increased risk of breast cancer ( judged on the basis of specific criteria ) . Eligible women were r and omly assigned ( 1:1 ) by central computer allocation to receive 1 mg oral anastrozole or matching placebo every day for 5 years . R and omisation was stratified by country and was done with blocks ( size six , eight , or ten ) . All trial personnel , participants , and clinicians were masked to treatment allocation ; only the trial statistician was unmasked . The primary endpoint was histologically confirmed breast cancer ( invasive cancers or non-invasive ductal carcinoma in situ ) . Analyses were done by intention to treat . This trial is registered , number IS RCT N31488319 . FINDINGS 1920 women were r and omly assigned to receive anastrozole and 1944 to placebo . After a median follow-up of 5·0 years ( IQR 3·0 - 7·1 ) , 40 women in the anastrozole group ( 2 % ) and 85 in the placebo group ( 4 % ) had developed breast cancer ( hazard ratio 0·47 , 95 % CI 0·32 - 0·68 , p<0·0001 ) . The predicted cumulative incidence of all breast cancers after 7 years was 5·6 % in the placebo group and 2·8 % in the anastrozole group . 18 deaths were reported in the anastrozole group and 17 in the placebo group , and no specific causes were more common in one group than the other ( p=0·836 ) . INTERPRETATION Anastrozole effectively reduces incidence of breast cancer in high-risk postmenopausal women . This finding , along with the fact that most of the side-effects associated with oestrogen deprivation were not attributable to treatment , provides support for the use of anastrozole in postmenopausal women at high risk of breast cancer . FUNDING Cancer Research UK , the National Health and Medical Research Council Australia , Sanofi-Aventis , and AstraZeneca PURPOSE Bisphosphonates prevent skeletal-related events in patients with metastatic breast cancer . Their effect in early breast cancer is controversial . Ib and ronate is an orally and intravenously available amino-bisphosphonate with a favorable toxicity profile . It therefore qualifies as potential agent for adjuvant use . PATIENTS AND METHODS The GAIN ( German Adjuvant Intergroup Node-Positive ) study was an open-label , r and omized , controlled phase III trial with a 2 × 2 factorial design . Patients with node-positive early breast cancer were r and omly assigned 1:1 to two different dose-dense chemotherapy regimens and 2:1 to ib and ronate 50 mg per day orally for 2 years or observation . In all , 2,640 patients and 728 events were estimated to be required to demonstrate an increase in disease-free survival ( DFS ) by ib and ronate from 75 % to 79.5 % by using a two-sided α = .05 and 1-β of 80 % . We report here the efficacy analysis for ib and ronate , which was released by the independent data monitoring committee because the futility boundary was not crossed after 50 % of the required DFS events were observed . RESULTS Between June 2004 and August 2008 , 2,015 patients were r and omly assigned to ib and ronate and 1,008 to observation . Patients r and omly assigned to ib and ronate showed no superior DFS or overall survival ( OS ) compared with patients r and omly assigned to observation ( DFS : hazard ratio , 0.945 ; 95 % CI , 0.768 to 1.161 ; P = .589 ; OS : HR , 1.040 ; 95 % CI , 0.763 to 1.419 ; P = .803 ) . DFS was numerically longer if ib and ronate was used in patients younger than 40 years or older than 60 years compared with patients age 40 to 59 years ( test for interaction P = .093 ) . CONCLUSION Adjuvant treatment with oral ib and ronate did not improve outcome of patients with high-risk early breast cancer who received dose-dense chemotherapy 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 There is strong evidence for the isolated tumour cells ( ITCs ) in the bone marrow of breast cancer patients having prognostic impact both at primary diagnosis and during recurrence-free follow-up . The goal of this study was to investigate the therapeutic efficacy of zoledronate on the persistence of ITC . PATIENTS AND METHODS A total of 172 primary breast cancer patients without evidence of distant recurrence but detection of ITC in bone marrow were followed up . Zoledronate was administered every 4 weeks for 6 months to 31 patients who had completed surgery and adjuvant chemotherapy . In a matched-pair analysis , these patients were compared to 141 patients who did not receive additional zoledronate treatment . The bone marrow was re-examined after a median of 7.9 months ( SD 0.89 ) and 11.5 months ( SD 12.41 ; p=0.11 ) , respectively . Patients were followed-up prospect ively for a median of 39 months after the first aspiration . RESULTS While ITCs were detected in all 172 patients at the time of first bone marrow aspiration , ITCs were detected in four patients ( 13 % ) following 6 months of zoledronate therapy in contrast to 38 patients ( 27 % ) of the control group ( p=0.099 ) . The reduction in cell numbers between the first and second aspiration reached statistical significance in the zoledronate group ( p=0.02 vs. p=0.14 ) . Persistent ITCs at the follow-up aspiration were associated with reduced recurrence-free survival ( p=0.05 ) . CONCLUSION These results indicate a potential antineoplastic effect of the cell cycle-independent agent zoledronate on persisting ITCs in a dormant state PURPOSE In the majority of premenopausal breast cancer patients , an adjuvant chemotherapy-induced early menopause occurs , which is known to be a strong predictor of osteoporosis . We present data on the effect of adjuvant cyclophosphamide , methotrexate , and fluorouracil ( CMF ) therapy on bone mineral density ( BMD ) and the efficacy of clodronate on the prevention of bone loss in 14 Output:	Compelling evidence from a meta- analysis of trial data of > 18,000 patients supports clinical ly significant benefits of bisphosphonates on the development of bone metastases and breast cancer mortality in post-menopausal women or those receiving ovarian suppression therapy .
MS21840	*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 whether a medication review by a specialized team would promote regimen changes in elders taking multiple medications and to measure the effect of regimen changes on monthly cost and functioning . DESIGN A r and omized-controlled trial . SETTING Health center ambulatory clinic . PARTICIPANTS Community-dwelling older adults taking five or more medications were assessed at baseline and 6 weeks . A medication-change intervention group of 57 elders was compared with a control group of 76 elder adults . INTERVENTION The primary intervention was a comprehensive review and recommended modification of a patient 's medication regimen . Changes were endorsed by each patient 's primary physician and discussed with each patient . MEASUREMENTS Measures were the Timed Manual Performance Test , Physical Performance Test , Functional Reach Assessment , subtests from the Wechsler Adult Intelligence Scale , a modified R and t Memory Test , the Center for Epidemiological Studies -Depression Scale , the Self-Rating Anxiety Scale , and the R and 36-item Health Survey 1.0 . Comorbidity was determined using the International Classification of Diseases , Ninth Revision , Clinical Modification . Medication usage was determined using brown bag review . RESULTS Intervention subjects decreased their medications by an average of 1.5 drugs . No differences in functioning were observed between groups . Intervention subjects saved an average $ 26.92 per month in wholesale medication costs ; control subjects saved $ 6.75 per month ( P<.006 ) . CONCLUSION Although the intervention significantly reduced the medications taken and monthly cost , most patients were resistant to reducing medications to the recommended level . Further study is needed to underst and patient resistance to reducing adverse polypharmacy and to devise better strategies for addressing this important problem in geriatric health . Greater focus on prescriber behavior is recommended Background : There is no single generally accepted clinical definition of frailty . Previously developed tools to assess frailty that have been shown to be predictive of death or need for entry into an institutional facility have not gained acceptance among practising clinicians . We aim ed to develop a tool that would be both predictive and easy to use . Methods : We developed the 7-point Clinical Frailty Scale and applied it and other established tools that measure frailty to 2305 elderly patients who participated in the second stage of the Canadian Study of Health and Aging ( CSHA ) . We followed this cohort prospect ively ; after 5 years , we determined the ability of the Clinical Frailty Scale to predict death or need for institutional care , and correlated the results with those obtained from other established tools . Results : The CSHA Clinical Frailty Scale was highly correlated ( r = 0.80 ) with the Frailty Index . Each 1-category increment of our scale significantly increased the medium-term risks of death ( 21.2 % within about 70 mo , 95 % confidence interval [ CI ] 12.5%–30.6 % ) and entry into an institution ( 23.9 % , 95 % CI 8.8%–41.2 % ) in multivariable models that adjusted for age , sex and education . Analyses of receiver operating characteristic curves showed that our Clinical Frailty Scale performed better than measures of cognition , function or comorbidity in assessing risk for death ( area under the curve 0.77 for 18-month and 0.70 for 70-month mortality ) . Interpretation : Frailty is a valid and clinical ly important construct that is recognizable by physicians . Clinical judgments about frailty can yield useful predictive information Background Computer-based decision support systems are a promising method for incorporating research evidence into clinical practice . However , evidence is still scant on how such information technology solutions work in primary healthcare when support is provided across many health problems . In Finl and , we design ed a trial where a set of evidence -based , patient-specific reminders was introduced into the local Electronic Patient Record ( EPR ) system . The aim was to measure the effects of such reminders on patient care . The hypothesis was that the total number of triggered reminders would decrease in the intervention group compared with the control group , indicating an improvement in patient care . Methods From July 2009 to October 2010 all the patients of one health center were r and omized to an intervention or a control group . The intervention consisted of patient-specific reminders concerning 59 different health conditions triggered when the healthcare professional ( HCP ) opened and used the EPR . In the intervention group , the triggered reminders were shown to the HCP ; in the control group , the triggered reminders were not shown . The primary outcome measure was the change in the number of reminders triggered over 12 months . We developed a unique data gathering method , the Repeated Study Virtual Health Check ( RSVHC ) , and used Generalized Estimation Equations ( GEE ) for analysing the incidence rate ratio , which is a measure of the relative difference in percentage change in the numbers of reminders triggered in the intervention group and the control group . Results In total , 13,588 participants were r and omized and included . Contrary to our expectation , the total number of reminders triggered increased in both the intervention and the control groups . The primary outcome measure did not show a significant difference between the groups . However , with the inclusion of patients followed up over only six months , the total number of reminders increased significantly less in the intervention group than in the control group when the confounding factors ( age , gender , number of diagnoses and medications ) were controlled for . Conclusions Computerized , tailored reminders in primary care did not decrease during the 12 months of follow-up time after the introduction of a patient-specific decision support system . Trial registration Clinical Trial.gov OBJECTIVES To describe patterns of comorbidity and multimorbidity in elderly people . DESIGN A community-based survey . SETTING Data were gathered from the Kungsholmen Project , a urban , community-based prospect i ve cohort in Sweden . PARTICIPANTS Adults aged 77 and older living in the community and in institutions of the geographically defined Kungsholmen area of Stockholm ( N=1,099 ) . MEASUREMENTS Diagnoses based on physicians ' examinations and supported by hospital records , drug use , and blood sample s. Patterns of comorbidity and multimorbidity were evaluated using four analytical approaches : prevalence figures , conditional count , logistic regression models , and cluster analysis . RESULTS Visual impairments and heart failure were the diseases with the highest comorbidity ( mean 2.9 and 2.6 co-occurring conditions , respectively ) , whereas dementia had the lowest ( mean 1.4 comorbidities ) . Heart failure occurred rarely without any comorbidity ( 0.4 % ) . The observed prevalence of comorbid pairs of conditions exceeded the expected prevalence for several circulatory diseases and for dementia and depression . Logistic regression analyses detected similar comorbid pairs . The cluster analysis revealed five clusters . Two clusters included vascular conditions ( circulatory and cardiopulmonary clusters ) , and another included mental diseases along with musculoskeletal disorders . The last two clusters included only one major disease each ( diabetes mellitus and malignancy ) together with their most common consequences ( visual impairment and anemia , respectively ) . CONCLUSION In persons with multimorbidity , there exists co-occurrence of diseases beyond chance , which clinicians need to take into account in their daily practice . Some pathological mechanisms behind the identified clusters are well known ; others need further clarification to identify possible preventative strategies BACKGROUND Older people consume an increasing amount of medication . Polypharmacy is associated with an elevated risk of adverse health outcomes result ing in hospitalizations and sometimes death . OBJECTIVES To describe the prevalence of prescribed and over-the-counter ( OTC ) medications among older general practice patients living in the community . To determine predictors of polypharmacy ( five or more prescribed drugs ) from a variety of patient- and doctor-related factors . METHODS Sixty-seven r and omly selected practice s in two areas of Germany and 466 of their older patients ( 70 + years ) were recruited for a geriatric assessment study . A cross-sectional analysis of health problems , GPs ' awareness and their interventions was conducted . In this post hoc analysis , we assessed the medication use as reported by older patients and compared it with doctors ' perceived medication regimens for their respective patients . The detailed assessment of patients ' health and well-being enabled us to explore a variety of predictors of polypharmacy using logistic regression analysis with forward selection . RESULTS Study participants consumed an average of 3.7 prescribed medicines and an additional 1.4 OTC drugs . In all , 26.7 % of patients used five and more chronically prescribed drugs . A set of five determinants predicted polypharmacy best : breathlessness , hypertension , dependency on instrumental activities of daily living , low subjective health and medication disagreement between doctors and patients . CONCLUSION This older general practice population in Germany is among the top pharmaceutical user group of European study sample s. Apart from disease-specific determinants , GPs should be aware that low subjective health and medication disagreement are independent predictors of polypharmacy Abstract Objective To ascertain the current burden of adverse drug reactions ( ADRs ) through a prospect i ve analysis of all admissions to hospital . Design Prospect i ve observational study . Setting Two large general hospitals in Merseyside , Engl and . Participants 18 820 patients aged > 16 years admitted over six months and assessed for cause of admission . Main outcome measures Prevalence of admissions due to an ADR , length of stay , avoidability , and outcome . Results There were 1225 admissions related to an ADR , giving a prevalence of 6.5 % , with the ADR directly leading to the admission in 80 % of cases . The median bed stay was eight days , accounting for 4 % of the hospital bed capacity . The projected annual cost of such admissions to the NHS is £ 466 m ( € 706 m , $ 847 m ) . The overall fatality was 0.15 % . Most reactions were either definitely or possibly avoidable . Drugs most commonly implicated in causing these admissions included low dose aspirin , diuretics , warfarin , and non-steroidal anti-inflammatory drugs other than aspirin , the most common reaction being gastrointestinal bleeding . Conclusion The burden of ADRs on the NHS is high , accounting for considerable morbidity , mortality , and extra costs . Although many of the implicated drugs have proved benefit , measures need to be put into place to reduce the burden of ADRs and thereby further improve the benefit : harm ratio of the drugs Background Disease management programmes ( DMPs ) are costly and impose additional work load on general practitioners ( GPs ) . Data on their effectiveness are inconclusive . We therefore conducted a cluster-r and omised controlled trial to evaluate the effectiveness of the Austrian DMP for diabetes mellitus type 2 on HbA1c and quality of care for adult patients in primary care . Methods All GPs of Salzburg-province were invited to participate . After cluster-r and omisation by district , all patients with diabetes type 2 were recruited consecutively from 7 - 11/2007 . The DMP , consisting mainly of physician and patient education , st and ardised documentation and agreement on therapeutic goals , was implemented in the intervention group while the control group received usual care . We aim ed to show superiority of the intervention regarding metabolic control and process quality . The primary outcome measure was a change in HbA1c after one year . Secondary outcomes were days in the hospital , blood pressure , lipids , body mass index ( BMI ) , enrolment in patient education and regular guideline -adherent examination . Blinding was not possible . Results 92 physicians recruited 1489 patients ( 649 intervention , 840 control ) . After 401 ± 47 days , 590 intervention- patients and 754 controls had complete data . In the intention to treat analysis ( ITT ) of all 1489 patients , HbA1c decreased 0.41 % in the intervention group and 0.28 % in controls . The difference of -0.13 % ( 95 % CI -0.24 ; -0.02 ) was significant at p = 0.026 . Significance was lost in mixed models adjusted for baseline value and cluster-effects ( adjusted mean difference -0.03 ( 95 % CI -0.15 ; 0.09 , p = 0.607 ) . Of the secondary outcome measures , BMI and cholesterol were significantly reduced in the intervention group compared to controls in ITT after adjustments ( -0.53 kg/m² ; 95 % CI -1.03;-0.02 ; p = 0.014 and -0.10 mmol/l ; 95 % CI -0.21 ; -0.003 ; p = 0.043 ) . Additionally , more patients received patient education ( 49.5 % vs. 20.1 % , p < 0.0001 ) , eye- ( 71.0 % vs. 51.2 % , p < 0.0001 ) , foot examinations ( 73.8 % vs. 45.1 % , p < 0.0001 ) , and regular HbA1c checks ( 44.1 % vs. 36.0 % , p < 0.01 ) in the intervention group . Conclusion The Austrian DMP implemented by statutory health insurance improves process quality and enhances weight reduction , but does not significantly improve metabolic control for patients with type 2 diabetes mellitus . Whether the small benefit seen in secondary outcome measures leads to better patient outcomes , remains unclear . Trial Registration Current Controlled trials Ltd. , IS RCT N27414162 INTRODUCTION STOPP ( Screening Tool of Older Persons ' potentially inappropriate Prescriptions ) is a new , systems-defined medicine review tool . We compared the performance of STOPP to that of established Beers ' criteria in detecting potentially inappropriate medicines ( PIMs ) Output:	Discussion The principal hypothesis is that reduction of polypharmacy and inappropriate prescribing can improve the clinical composite outcome of hospitalization or death . A positive result of the trial will contribute substantially to the improvement of care in multimorbidity .
MS21841	*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 the study was to investigate test reliability of the Yo-Yo intermittent recovery test level 1 ( YYIR1 ) in 36 high-level youth soccer players , aged between 13 and 18 years . Players were divided into three age groups ( U15 , U17 and U19 ) and completed three YYIR1 in three consecutive weeks . Pairwise comparisons were used to investigate test reliability ( for distances and heart rate responses ) using technical error ( TE ) , coefficient of variation ( CV ) , intra-class correlation ( ICC ) and limits of agreement ( LOA ) with Bl and -Altman plots . The mean YYIR1 distances for the U15 , U17 and U19 groups were 2024 ± 470 m , 2404 ± 347 m and 2547 ± 337 m , respectively . The results revealed that the TEs varied between 74 and 172 m , CVs between 3.0 and 7.5 % , and ICCs between 0.87 and 0.95 across all age groups for the YYIR1 distance . For heart rate responses , the TEs varied between 1 and 6 bpm , CVs between 0.7 and 4.8 % , and ICCs between 0.73 and 0.97 . The small ratio LOA revealed that any two YYIR1 performances in one week will not differ by more than 9 to 28 % due to measurement error . In summary , the YYIR1 performance and the physiological responses have proven to be highly reliable in a sample of Belgian high-level youth soccer players , aged between 13 and 18 years . The demonstrated high level of intermittent endurance capacity in all age groups may be used for comparison of other prospect i ve young soccer players Validity and Reproducibility of the Sargent Jump Test in the Assessment of Explosive Strength in Soccer Players The purpose of this study was to check the validity and the intra- and inter-evaluators reproducibility of the Sargent Jump Test , as an instrument of explosive strength measurement of soccer players of the sub-15 class . Forty-five soccer players were r and omly selected from different clubs competing in the local soccer championship . All subjects performed one test on the same jump platform model Jumptest ® ( Hidrofit Ltda , Brazil ) and two independent Sargent Jump Tests assessed by the same evaluator . Two days later , another Sargent Jump Test was performed simultaneously assessed by 2 evaluators . In all tests , three jumps were performed and the highest one was registered . In order to check the validity , the first Sargent Jump Test results were compared to those from the jump platform , considered the gold st and ard . To evaluate intra- and inter-evaluator reproducibility , results from the first , second and third Sargent Jump Tests were analyzed . The validity and reproducibility were evaluated by intraclass correlation coefficients ( ICC ) , and by the Bl and and Altman test ( statistical pack SPSS 11.0 ) , with a significance level set at p<0.05 . The values found for validity ( r=0.99 , p=0.001 ) , for intra-evaluator reproducibility ( r=0.99 , p=0.001 ) and for inter-evaluator reproducibility ( r=1.0 , p=0.001 ) , permitted us to conclude that the Sargent Jump Test is a valid and reproducible instrument for measuring the explosive strength in homogeneous groups , such as those used in the present study Objectives For the measurement of patient-reported outcomes , such as ( health-related ) quality of life , often many measurement instruments exist that intend to measure the same construct . To facilitate instrument selection , our aim was to develop a highly sensitive search filter for finding studies on measurement properties of measurement instruments in PubMed and a more precise search filter that needs less abstract s to be screened , but at a higher risk of missing relevant studies . Methods A r and om sample of 10,000 PubMed records ( 01 - 01 - 1990 to 31 - 12 - 2006 ) was used as a gold st and ard . Studies on measurement properties were identified using an exclusion filter and h and search ing . Search terms were selected from the relevant records in the gold st and ard as well as from 100 systematic review s of measurement properties and combined based on sensitivity and precision . The performance of the filters was tested in the gold st and ard as well as in two validation sets , by calculating sensitivity , precision , specificity , and number needed to read . Results We identified 116 studies on measurement properties in the gold st and ard . The sensitive search filter was able to retrieve 113 of these 116 studies ( sensitivity 97.4 % , precision 4.4 % ) . The precise search filter had a sensitivity of 93.1 % and a precision of 9.4 % . Both filters performed very well in the validation sets . Conclusion The use of these search filters will contribute to evidence -based selection of measurement instruments in all medical fields Prediction of adult performance from early age talent identification in sport remains difficult . Talent identification research has generally been performed using univariate analysis , which ignores multivariate relationships . To address this issue , this study used a novel higher-dimensional model to orthogonalize multivariate anthropometric and fitness data from junior rugby league players , with the aim of differentiating future career attainment . Anthropometric and fitness data from 257 Under-15 rugby league players was collected . Players were grouped retrospectively according to their future career attainment ( i.e. , amateur , academy , professional ) . Players were blindly and r and omly divided into an exploratory ( n = 165 ) and validation data set ( n = 92 ) . The exploratory data set was used to develop and optimize a novel higher-dimensional model , which combined singular value decomposition ( SVD ) with receiver operating characteristic analysis . Once optimized , the model was tested using the validation data set . SVD analysis revealed 60 m sprint and agility 505 performance were the most influential characteristics in distinguishing future professional players from amateur and academy players . The exploratory data set model was able to distinguish between future amateur and professional players with a high degree of accuracy ( sensitivity = 85.7 % , specificity = 71.1 % ; p<0.001 ) , although it could not distinguish between future professional and academy players . The validation data set model was able to distinguish future professionals from the rest with reasonable accuracy ( sensitivity = 83.3 % , specificity = 63.8 % ; p = 0.003 ) . Through the use of SVD analysis it was possible to objective ly identify criteria to distinguish future career attainment with a sensitivity over 80 % using anthropometric and fitness data alone . As such , this suggests that SVD analysis may be a useful analysis tool for research and practice within talent identification PURPOSE To examine the physiological response and reproducibility of the Yo-Yo intermittent recovery test and its application to elite soccer . METHODS Heart rate was measured , and metabolites were determined in blood and muscle biopsies obtained before , during , and after the Yo-Yo test in 17 males . Physiological measurements were also performed during a Yo-Yo retest and an exhaustive incremental treadmill test ( ITT ) . Additionally , 37 male elite soccer players performed two to four seasonal tests , and the results were related to physical performance in matches . RESULTS The test-retest CV for the Yo-Yo test was 4.9 % . Peak heart rate was similar in ITT and Yo-Yo test ( 189 + /- 2 vs 187 + /- 2 bpm ) , whereas peak blood lactate was higher ( P < 0.05 ) in the Yo-Yo test . During the Yo-Yo test , muscle lactate increased eightfold ( P < 0.05 ) and muscle creatine phosphate ( CP ) and glycogen decreased ( P < 0.05 ) by 51 % and 23 % , respectively . No significant differences were observed in muscle CP , lactate , pH , or glycogen between 90 and 100 % of exhaustion time . During the precompetition period , elite soccer players improved ( P < 0.05 ) Yo-Yo test performance and maximum oxygen uptake ( [OV0312]O(2max ) ) by 25 + /- 6 and 7 + /- 1 % , respectively . High-intensity running covered by the players during games was correlated to Yo-Yo test performance ( r = 0.71 , P < 0.05 ) but not to [OV0312]O(2max ) and ITT performance . CONCLUSION The test had a high reproducibility and sensitivity , allowing for detailed analysis of the physical capacity of athletes in intermittent sports . Specifically , the Yo-Yo intermittent recovery test was a valid measure of fitness performance in soccer . During the test , the aerobic loading approached maximal values , and the anaerobic energy system was highly taxed . Additionally , the study suggests that fatigue during intense intermittent short-term exercise was unrelated to muscle CP , lactate , pH , and glycogen Markovic , G and Mikulic , P. Discriminative ability of the Yo-Yo intermittent recovery test ( level 1 ) in prospect i ve young soccer players . J Strength Cond Res 25(10 ) : 2931–2934 , 2011—We evaluated the sensitivity of the Yo-Yo intermittent recovery test-level 1 ( Yo-Yo IR1 ) when discriminating among players in varying playing positions and different age categories in youth soccer . One-hundred and six prospect i ve young soccer players , grouped on the basis of chronological age ( under-13 , under-14 , under-15 , under-16 , under-17 , under-18 , and under-19 ) and playing position ( center-backs , fullbacks , center midfielders , wide midfielders , and forwards ) , participated in the study . The players were administered a single Yo-Yo IR1 test at the beginning of the spring season . Analysis of variance revealed significant ( F = 25.3 ; p < 0.001 ) group differences in Yo-Yo IR1 test performance scores among the observed age categories , and a systematic age-related increase in the Yo-Yo IR1 test performance was evident . Subsequent post hoc comparisons identified a number of significant differences among the selected age categories in Yo-Yo IR1 test performance . Analysis of covariance identified significant differences among playing positions ( F = 3.1 ; p < 0.019 ) in the Yo-Yo IR1 test performance after controlling for age ( F = 135.1 ; p < 0.001 ) . Subsequent pairwise comparisons of the adjusted Yo-Yo IR1 test performance identified that center-backs had achieved significantly lower ( all p < 0.01 ) performance scores than center midfielders , wide midfielders , and forwards , but not fullbacks . These results could be of practical value to coaches and scientists for further development of talent selection and profiling procedures in soccer , particularly because ( a ) the endurance performance represents a very important fitness component in selection and profiling of young soccer players and ( b ) the Yo-Yo IR1 test proved to be valid , reliable , and easily available measurement tool of a player 's soccer-specific endurance capacity PURPOSE To examine the physiological response , reliability , and validity of the Yo-Yo intermittent recovery level 2 test ( Yo-Yo IR2 ) . METHODS Thirteen normally trained male subjects carried out four Yo-Yo IR2 tests , an incremental treadmill test ( ITT ) , and various sprint tests . Muscle biopsies and blood sample s were obtained , and heart rate was measured before , during , and after the Yo-Yo IR2 test . Additionally , 119 Sc and inavian elite soccer players carried out the Yo-Yo IR2 test on two to four occasions . RESULTS Yo-Yo IR2 performance was 591 + /- 43 ( 320 - 920 ) m or 4.3 ( 2.6 - 7.9 ) min . Test-retest coefficient of variation in distance covered was 9.6 % ( N = 29 ) . Heart rate ( HR ) at exhaustion was 191 + /- 3 bpm , or 98 + /- 1 % HRmax . Muscle lactate was 41.7 + /- 5.4 and 68.5 + /- 7.6 mmol x kg(-1 ) d.w . at 85 and 100 % of exhaustion time , respectively , with corresponding muscle CP values of 40.4 + /- 5.2 and 29.4 + /- 4.7 mmol x kg(-1 ) d.w . Peak blood lactate was 13.6 + /- 0.5 mM. Yo-Yo IR2 performance was correlated to ITT performance ( r = 0.74 , P < 0.05 ) and VO2max ( r = 0.56 , P < 0.05 ) but not to 30- and 50-m sprint performance . Yo-Yo IR2 performance was better ( P < 0.05 ) for international elite soccer players than for moderate elite players ( 1059 + /- 35 vs 771 + /- 26 m ) and better ( P < 0.05 ) for central defenders ( N = 21 ) , fullbacks ( N = 20 ) , and midfielders ( N = 48 ) than for goal keepers ( N = 6 ) and attackers ( N = 24 ) . Fifteen elite soccer players improved ( P < 0.05 ) Yo-Yo IR2 performance by 42 + /- 8 % during 8 wk of preseasonal training . CONCLUSION This study demonstrates that the Yo-Yo IR2 test is reproducible and can be used to evaluate an athlete 's ability to perform intense intermittent exercise with a high rate of aerobic and anaerobic energy turnover . Specifically , the Yo-Yo IR2 test was shown to be a sensitive tool to differenti Output:	There was limited evidence found for the reliability and /or validity of 5 m , 10 m , 20 m speed tests , 505 test , modified 505 test , L run test , Sergeant Jump test and bench press repetitions-to-fatigue tests . There was no information from high- quality studies on the measurement properties of all the other tests identified in stage 1 . However , there is paucity of information on measurement properties from high- quality studies for the tests .
MS21842	*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 Fruit and vegetables is a heterogeneous food group with different content of dietary fiber , vitamins , minerals , carotenoids , and bioactive phytochemicals . Our objective was to examine the relation between specific consumption of fruit and vegetable subgroups and stroke risk in a cohort of Swedish women and men . METHODS AND RESULTS We prospect ively followed 74,961 participants ( 34,670 women and 40,291 men ) who had completed a food frequency question naire in the autumn of 1997 and were free from stroke , coronary heart disease , and cancer at baseline . Diagnoses of stroke in the cohort during follow-up were ascertained from the Swedish Hospital Discharge Registry . A total of 4089 stroke cases , including 3159 cerebral infa rct ions , 435 intracerebral hemorrhages , 148 subarachnoid hemorrhages , and 347 unspecified strokes , were ascertained during 10.2 years of follow-up . The multivariable relative risk ( RR ) of total stroke for the highest vs. lowest category of total fruit and vegetable consumption was 0.87 ( 95 % confidence interval [ CI ] 0.78 - 0.97 ; P for trend = 0.01 ) . The association was confined to individuals without hypertension ( corresponding RR , 0.81 ; 95 % CI , 0.71 - 0.93 ; P for trend = 0.01 ) . Among individual fruits and vegetable subgroups , inverse associations with total stroke were observed for apples/pears ( RR , 0.89 ; 95 % CI , 0.80 - 0.98 ; P for trend = 0.02 ) and green leafy vegetables ( RR , 0.92 ; 95 % CI , 0.81 - 1.04 ; P for trend = 0.03 ) . CONCLUSION This study shows an inverse association of fruit and vegetable consumption with stroke risk . Particularly consumption of apples and pears and green leafy vegetables was inversely associated with stroke Increased fruit and vegetable consumption may protect against lung cancer , although epidemiologic findings are inconclusive . The authors prospect ively examined associations between lung cancer risk and intakes of fruit , vegetables , and botanical subgroups in 472,081 participants aged 50 - 71 years in the National Institutes of Health (NIH)-AARP Diet and Health Study . Diet was assessed at baseline ( 1995 - 1996 ) with a 124-item dietary question naire . A total of 6,035 incident lung cancer cases were identified between 1995 and 2003 . Total fruit and vegetable intake was unrelated to lung cancer risk in both men and women . Higher consumption of several botanical subgroups , however , was significantly inversely associated with risk , but only in men . For example , the relative risks of lung cancer among men in the highest versus lowest quintiles of intake of rosaceae , convolvulaceae , and umbelliferae were 0.82 ( 95 % confidence interval ( CI ) : 0.73 , 0.91 ) , 0.86 ( 95 % CI : 0.75 , 0.96 ) , and 0.86 ( 95 % CI : 0.78 , 0.96 ) , respectively ; corresponding relative risks in women were 0.97 ( 95 % CI : 0.85 , 1.12 ) , 0.95 ( 95 % CI : 0.83 , 1.09 ) , and 0.92 ( 95 % CI : 0.80 , 1.06 ) . These results provide support for a protective role of specific botanical subgroups of fruits and vegetables in lung cancer prevention in men , although the findings could also be due to residual confounding by smoking or chance BACKGROUND There is probable evidence that some types of fruit and vegetables provide protection against many cancers . OBJECTIVE We hypothesized that fruit and vegetable intakes are inversely related to the incidence of total cancers among women and men aged > 50 y. DESIGN We performed a prospect i ve study among the cohort of the National Institutes of Health-AARP Diet and Health Study . We merged the MyPyramid Equivalents Data base ( version 1.0 ) with food-frequency- question naire data to calculate cup equivalents for fruit and vegetables . From 1995 to 2003 , we identified 15,792 and 35,071 cancer cases in 195,229 women and 288,109 men , respectively . We used Cox proportional hazards models to estimate multivariate relative risks ( RRs ) and 95 % CIs associated with the highest compared with the lowest quintile ( Q ) of fruit and vegetable intakes . RESULTS Fruit intake was not associated with the risk of total cancer among women ( RR(Q5 vs Q1 ) = 0.99 ; 95 % CI : 0.94 , 1.05 ; P trend = 0.059 ) or men ( RR(Q5 vs Q1 ) = 0.98 ; 95 % CI : 0.95 , 1.02 ; P for trend = 0.17 ) . Vegetable intake was not associated with risk of total cancer among women ( RR(Q5 vs Q1 ) = 1.04 ; 95 % CI : 0.98 , 1.09 ; P for trend = 0.084 ) , but was associated with a significant decrease in risk in men ( RR(Q5 vs Q1 ) = 0.94 ; 95 % CI : 0.91 , 0.97 ; P trend = 0.004 ) . This significant finding among men was no longer evident when we limited the analysis to men who never smoked ( RR(Q5 vs Q1 ) = 0.97 ; 95 % CI : 0.91 , 1.04 ; P for trend = 0.474 ) . CONCLUSIONS Intake of fruit and vegetables was generally unrelated to total cancer incidence in this cohort . Residual confounding by smoking is a likely explanation for the observed inverse association with vegetable intake among men Objectives : To determine the patterns and possible explanations for gender differences in food choices , nutrient intakes and status indices , especially for micronutrients , in a representative sample of older people living in Britain , who participated in the National Diet and Nutrition Survey of people aged 65 y and over during 1994–95 . Design : The Survey procedures included a health- and -lifestyle interview , a four-day weighed diet record , anthropometric measurements and a fasting blood sample for biochemical indices . Setting : Eighty r and omly-selected postcode sectors from mainl and Britain . Subjects : Of 1556 older people not living in institutions who were interviewed , 80 % agreed to provide a complete four-day diet record and 63 % agreed to give a blood sample for status index measurements . Interventions : None . Main result : The most highly significant gender differences in food choices were that women ate more butter , full-fat milk and certain beverages , cakes , apples , pears and bananas , whereas men ate more eggs , sugar , certain meat products and drank more alcoholic drinks , especially beer and lager . When adjusted for energy intakes , the younger women ( 65–79 y ) had higher intakes than the younger men , of fat , retinol , vitamin C and calcium . The older women ( 80+y ) had higher intakes than older men , of fat and vitamin E , but lower intakes of protein , zinc and β-carotene . The younger women had better status indices than the younger men : for α- and β-carotenes , β-cryptoxanthin and vitamin C. Women had higher plasma concentrations of cholesterol and HDL cholesterol , phosphate and copper , but lower indices of iron and vitamin D status , than men . These gender differences in status were not altered by inclusion of the corresponding nutrient intakes in the model . Conclusions : There are gender differences in food choices , in energy and nutrient intakes and in nutritional blood status indices in older British people , especially those aged 65–79 y. Some of the status differences are attenuated in the age group of 80 y and older , whereas others are enhanced . The relationships between the quantity and type of foods or nutrients consumed , and nutrient status , are complex . With respect to suspected risk and protective factors for vascular disease , women aged 65–79 y had significantly better status for plasma α- and β-carotene , ascorbate , HDL-cholesterol and homocysteine ; but , in contrast , they had lower blood haemoglobin concentrations and higher concentrations of total and non-HDL-cholesterol . Sponsorship : The British National Diet and Nutrition Survey series is funded by the Ministry of Agriculture , Fisheries and Food and the Department of Health , and this survey was conducted by Social and Community Planning Research in conjunction with MRC Human Nutrition Research ( formerly MRC Dunn Nutritional Laboratory ) Abstract Epidemiological studies have shown an inverse correlation between a fruit and vegetable-rich diet and cardiovascular diseases ; this beneficial effect of fruits and vegetables is probably due to the presence of antioxidant phytochemicals . In contrast , cigarette smoking is a high risk factor for lung and heart diseases , associated with chronic oxidative stress . In the present study , the effect of the consumption of a pear , an apple and 200 ml orange juice , during 26 days , on total plasma antioxidant capacity ( TAC ) and lipid profile of chronic smokers and non-smoking healthy adults was analyzed . Fruit consumption increased TAC in non-smokers , but not in smokers . In non-smokers , total cholesterol , high-density lipoprotein-cholesterol , and low-density lipoprotein-cholesterol increased significantly ; while in smokers , total cholesterol and low-density lipoprotein-cholesterol decreased . We may conclude fruit/juice supplementation showed different effects , depending on the smoking habit : in non-smokers it increased TAC and cholesterol ; in smokers it reduced cholesterol , whithout inducing a TAC increase The association of fruit and vegetable consumption and lung cancer incidence was evaluated using the most recent data from the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) , applying a refined statistical approach ( calibration ) to account for measurement error potentially introduced by using food frequency question naire data . Between 1992 and 2000 , detailed information on diet and life-style of 478,590 individuals participating in EPIC was collected . During a median follow-up of 6.4 years , 1,126 lung cancer cases were observed . Multivariate Cox proportional hazard models were applied for statistical evaluation . In the whole study population , fruit consumption was significantly inversely associated with lung cancer risk while no association was found for vegetable consumption . In current smokers , however , lung cancer risk significantly decreased with higher vegetable consumption ; this association became more pronounced after calibration , the hazard ratio ( HR ) being 0.78 ( 95 % CI 0.62 - 0.98 ) per 100 g increase in daily vegetable consumption . In comparison , the HR per 100 g fruit was 0.92 ( 0.85 - 0.99 ) in the entire cohort and 0.90 ( 0.81 - 0.99 ) in smokers . Exclusion of cases diagnosed during the first 2 years of follow-up strengthened these associations , the HR being 0.71 ( 0.55 - 0.94 ) for vegetables ( smokers ) and 0.86 ( 0.78 - 0.95 ) for fruit ( entire cohort ) . Cancer incidence decreased with higher consumption of apples and pears ( entire cohort ) as well as root vegetables ( smokers ) . In addition to an overall inverse association with fruit intake , the results of this evaluation add evidence for a significant inverse association of vegetable consumption and lung cancer incidence in smokers BACKGROUND Most infants consume fruit juices by 6 months of age . However , fruit juices containing sorbitol may be associated with carbohydrate malabsorption without clinical symptoms . We hypothesized that increased physical activity and metabolic rate may be associated with carbohydrate malabsorption . METHODS Physical activity and metabolic rate were determined in 14 healthy infants ( [ mean + /- SD ] age , 5.1 + /- 0.8 months ; weight , 7.8 + /- 1.1 kg ; length , 67 + /- 4.2 cm ; and body fat , 26 % + /- 5 % ) for 3 hours in a respiratory chamber . Seven were fed pear juice , and the other 7 were fed white grape juice ( 120 mL ) after a 2-hour fast . Pear juice contains sorbitol and a high fructose-glucose ratio , whereas white grape juice is sorbitol free and has a low fructose-glucose ratio . Carbohydrate absorption was determined by breath hydrogen gas analysis . The study was double-blinded . RESULTS When compared with the infants without carbohydrate malabsorption ( peak breath hydrogen level < 20 ppm above baseline ) , 5 of the 7 infants fed pear juice and 2 of the 7 infants fed white grape juice exhibited carbohydrate malabsorption ( peak breath hydrogen level > or = 20 ppm above baseline ; P < .01 ) . These infants also exhibited both increased physical activity ( P < .001 ) and metabolic rate ( P < .05 ) after juice consumption in comparison with infants with normal Output:	Pears , similar to apples , are concentrated in fructose , and the high fiber and fructose in pears probably explain the laxative properties . Pears contain antioxidants and provide between 27 and 41 mg of phenolics per 100 g. Animal studies with pears suggest that pears may regulate alcohol metabolism , protect against ulcers , and lower plasma lipids .
MS21843	*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: Ar and omized , controlled study of 12 patients with mild chronic renal failure was design ed to assess the metabolic effects of a low-protein diet supplemented ( n = 6 ) or not ( n = 6 ) with ketoanalogs of amino acids . The protein intake was prescribed so that both groups were isonitrogenous . The dietary survey each month included a 3-d food record and a 24-h urine collection for urea measurement . After a 4- to 6-wk equilibrium period ( st and ard occidental diet , 1.11 g of protein and 32 kcal/kg per d ) , patients reduced their protein intake to reach 0.71 g of protein/kg per d during the third month . Energy intake was kept constant ( 31 kcal/kg per d ) during the 3-mo period . Compliance to the diet was achieved after 2 mo of training . Leucine turnover measurement was performed before and at the end of the 3-mo low-protein period . There was no clinical change , whereas total body flux decreased by 8 % ( P < 0.05 ) and leucine oxidation by 18 % ( P < 0.05 ) . No difference could be attributed to the ketoanalogs themselves . Thus , under sufficient energy intake , a low-protein diet is nutritionally and metabolically safe during chronic renal failure . The nitrogen-sparing effect of a low-protein diet is still present during mild chronic renal insufficiency In 15 ambulatory patients with renal insufficiency ( creatinine clearance , 9.9 + /- 3.0 ml/min ) the effect of oral supplementation with alpha-ketoacids has been compared with that of placebo . The protein intake amounted to 0.55 g protein per kilogram body weight of high biological value , as estimated by dietary recordings . After a control period of 3 months the patients received , in a double-blind study , 1.05 g alpha-ketoacids/10 kg body weight per day or a placebo for 6 weeks with a subsequent cross-over . Fasting blood sample s were analyzed at 3-week intervals for routine laboratory parameters and 17 proteins . Anthropometric and clinical data have been recorded every 3 weeks . While therapy with alpha-ketoacids diminished PO4 levels ( P less than 0.05 ) , no other significant effect could be demonstrated . No signs of protein deficiency existed either before or during alpha-ketoacid therapy . Therefore , supplementation with alpha-ketoacids appears to be superfluous in patients with renal insufficiency maintained on a 40-g protein diet Blood pressure ( BP ) is hardly controlled in chronic kidney disease ( CKD ) . We compared the effect of very low protein diet ( VLPD ) supplemented with ketoanalogs of essential amino acids ( 0.35 g/kg/day ) , low protein diet ( LPD , 0.60 g/kg/day ) , and free diet ( FD ) on BP in patients with CKD stages 4 and 5 . Vegetable proteins were higher in VLPD ( 66 % ) than in LPD ( 48 % ) . LPD was prescribed to 110 consecutive patients ; after run-in , they were invited to start VLPD . Thirty subjects accepted ; 57 decided to continue LPD ; 23 refused either diet ( FD group ) . At baseline , protein intake ( g/kg/day ) was 0.79+/-0.09 in VLPD , 0.78+/-0.11 in LPD , and 1.11+/-0.18 in FD ( P<0.0001 ) . After 6 months , protein intake was lower in VLPD than LPD and FD ( 0.54+/-0.11 , 0.78+/-0.10 , and 1.04+/-0.21 g/kg/day , respectively ; P<0.0001 ) . BP diminished only in VLPD , from 143+/-19/84+/-10 to 128+/-16/78+/-7 mm Hg ( P<0.0001 ) , despite reduction of antihypertensive drugs ( from 2.6+/-1.1 to 1.8+/-1.2 ; P<0.001 ) . Urinary urea excretion directly correlated with urinary sodium excretion , which diminished in VLPD ( from 181+/-32 to 131+/-36 mEq/day ; P<0.001 ) . At multiple regression analysis ( R2=0.270 , P<0.0001 ) , BP results independently related to urinary sodium excretion ( P=0.023 ) and VLPD prescription ( P=0.003 ) , but not to the level of protein intake . Thus , in moderate to advanced CKD , VLPD has an antihypertensive effect likely due to reduction of salt intake , type of proteins , and ketoanalogs supplementation , independent of actual protein intake BACKGROUND AND OBJECTIVES High levels of fibroblast growth factor 23 are associated with mortality , CKD progression , and calcification in CKD patients . The aim of this pilot study is to assess whether a very-low-protein diet ( 0.3 g/kg per day ) with a consequent low intake of phosphorus would reduce fibroblast growth factor 23 compared with a low-protein diet ( 0.6 g/kg per day ) in CKD patients not yet on dialysis . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS A prospect i ve , r and omized , controlled crossover study was performed in which 32 patients were r and omized into two groups . Group A ( 16 patients ) received a very-low-protein diet ( 0.3 g/kg body wt per day ) supplemented with ketoanalogues during the first week and a low-protein diet during the second week , and group B ( 16 patients ) received a low-protein diet during the first week and a very-low-protein diet during the second week . Fibroblast growth factor 23 , seric , and urinary phosphate levels were measured at baseline and the end of each study period . RESULTS After only 1 week of the very-low-protein diet , reductions in fibroblast growth factor 23 levels ( 33.5 % ) , serum phosphate ( 12 % ) , and urinary phosphate ( 34 % ) with the very-low-protein diet compared with the low-protein diet were observed . Serum and urinary phosphate levels and protein intake were significant determinants of fibroblast growth factor 23 ( 95 % confidence interval=1.04 - 1.19 , 1.12 - 1.37 , and 1.51 - 2.23 , respectively ) . CONCLUSIONS A very-low-protein diet supplemented with ketoanalogues reduced fibroblast growth factor 23 levels in CKD patients not yet on dialysis OBJECTIVE To compare a severe protein restriction diet supplemented with ketoanalogues to a moderate protein restriction diet in order to limit glomerular filtration rate ( GFR ) decrease in an advanced renal insufficiency stage . DESIGN Prospect i ve r and omised study conducted to compare a severe protein restriction diet ( 0.30 g/kg/day ) supplemented with a preparation of ketoanalogues , hydroxyanalogues of aminoacids and aminoacids ( Group A ) to a moderate protein restriction diet ( 0.65 g/kg/day ) ( Group B ) . PATIENTS 50 uremic patients included ( 25 in each group ) with GFR is < 20 mL/min/1.73m2 . RESULTS There were no statistically significant differences between the two dietary regimens for the renal survival . But uremia decreased significantly in Group A ( 22.7+/-5.2 to 18.5+/-6.7 mmol/L ) and increased in Group B ( 26.8+/-9.0 to 34.9+/-9.9 mmol/L ) . Calcemia increased in Group A from 2.28+/-0.18 to 2.42+/-0.17 mmol/L , p<0.01 with a stable phosphoremia while calcemia decreased in Group B ( 2.33+/-0.18 to 2.25+/-0.17 mmol/L , p<0.05 ) . At the end of the study , Group A was different from Group B for calcemia ( 2.42+/-0.17 vs. 2.25+/-0.17 mmol/L , p<0.01 ) , phosphoremia ( 1.39+/-0.30 vs. 1.80+/-0.65 mmol/L , p<0.02 ) , alkaline phosphatase ( 61.42+/-22.93 vs. 78.8+/-27.0 , p<0.05 ) and parathormone plasma levels ( 2.71+/-1.55 vs. 5.91+/-1.41 ng/mL , p<0.001 ) . COMMENTS Compared to a moderate protein restriction ( 0.65 g/kg/day ) , a severe protein restriction ( 0.3 g/kg/day ) supplemented by ketoanologues does not limit GFR decrease when GFR is below 20 mL/min/1.73m2 , but improves phosphocalcic plasma parameters The therapeutical effect of keto acids on bone histology was investigated in a prospect i ve r and omized controlled study of 40 patients . A marked improvement in osteofibrotic as well as in osteomalacic changes was found in bone biopsies after 12 months of treatment with keto acids OBJECTIVE To investigate if a-keto/amino acid supplemented low protein diet can slow down the progression of diabetic nephrophathy in comparison with non-supplemented diabetes diet . METHODS A prospect i ve , r and omized , controlled clinical study was conducted . Twenty three cases of type 2 diabetic nephropathy in IV stage were r and omly divided into alpha-keto/amino acid supplemented diet group ( trial group ) and conventional diabetes diet group ( control group ) , The treatment duration was 52 weeks . 24 h urine protein was measured at 0 , 12 , 20 , 36 and 52 weeks . Before and after the 52 weeks treatment , all the patients received the measurement of glomerular filtration rate ( GFR ) , blood glucose , blood lipids , inflammatory markers , as well as nutritional status . RESULTS After the treatment for 20 , 36 , 52 weeks , mean 24 h urine protein decreased significantly in trial groups ( P < 0.05 ) , and 24 h urine protein in trial group were significantly decreased ( P < 0.05 ) compared with control group in 20 weeks after treatment . Either in trial group or in control group , GFR remained relatively stable during the observation period . Nutrition status , inflammatory markers , and serum calcium , phosphorus levels between the two groups were no significantly difference . The adverse events experienced by the patients in trial group were similar and consistent with the patients underlying renal diseases . CONCLUSION Alpha-keto/amino acid can reduce proteinuria more effectively , while improve renal function and nutritional status in diabetic nephropathy patients with well-toleration Objective : To evaluate the effects on the nutritional and metabolic parameters of a very-low-protein diet supplemented with ketoacids ( VLPD+KA ) in comparison with a conventional low-protein diet ( LPD ) in chronic kidney disease ( CKD ) patients . Design : Prospect i ve , r and omized , controlled clinical study . Setting : Outpatient Clinic of the Nephrology Division of Federal University of São Paulo , Brazil . Subjects : The study involved 24 patients with advanced CKD ( creatinine clearance < 25 ml/min ) that were r and omly assigned to either a VLPD+KA ( VLPD+KA group , 12 patients ) or to a conventional LPD with 0.6 g/kg/day ( LPD group , 12 patients ) . The patients were followed for 4 months . Results : Nutritional status was adequately maintained with both diets for the studied period . Protein intake and serum urea nitrogen decreased significantly only in the VLPD+KA group ( from 0.68±0.17 to 0.43±0.12 g/kg/day , P<0.05 ; from 61.4±12.8 to 43.6±14.9 mg/dl , P<0.001 ; respectively ) . Ionized calcium did not change in the VLPD+KA group but tended to decrease in the LPD group . Serum phosphorus tended to decrease in the VLPD+KA group probably as a result of a significant reduction in dietary phosphorus ( 529±109 to 373±125 mg/day , P<0.05 ) associated to the phosphorus-binding effect of the ketoacids . No change in these parameters was found in the LPD group . Serum parathormone increased significantly only in the LPD group ( from 241±138 to 494±390 pg/ml , P<0.01 ) . The change in PTH concentration was negatively correlated with changes in ionized calcium concentration ( r=−0.75 , P=0.02 ) and positively correlated with changes in serum phosphorus ( r=0.71 , P=0.03 ) only in the LPD group . Con Output:	Conclusion Restricted protein diet supplemented with keto analogues ( s(v)LPD ) could delay the progression of CKD effectively without causing malnutrition
MS21844	*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 PURPOSE : The optimal paradigm choice for language mapping in clinical fMRI studies is challenging due to the variability in activation among different paradigms , the contribution to activation of cognitive processes other than language , and the difficulties in monitoring patient performance . In this study , we compared language localization and lateralization between 2 commonly used clinical language paradigms and 3 newly design ed dual-choice semantic paradigms to define a streamlined and adequate language -mapping protocol . MATERIAL S AND METHODS : Twelve healthy volunteers performed 5 language paradigms : Silent Word Generation , Sentence Completion , Visual Antonym Pair , Auditory Antonym Pair , and Noun-Verb Association . Group analysis was performed to assess statistically significant differences in fMRI percentage signal change and lateralization index among these paradigms in 5 ROIs : inferior frontal gyrus , superior frontal gyrus , middle frontal gyrus for expressive language activation , middle temporal gyrus , and superior temporal gyrus for receptive language activation . RESULTS : In the expressive ROIs , Silent Word Generation was the most robust and best lateralizing paradigm ( greater percentage signal change and lateralization index than semantic paradigms at P < .01 and P < .05 levels , respectively ) . In the receptive region of interest , Sentence Completion and Noun-Verb Association were the most robust activators ( greater percentage signal change than other paradigms , P < .01 ) . All except Auditory Antonym Pair were good lateralizing tasks ( the lateralization index was significantly lower than other paradigms , P < .05 ) . CONCLUSIONS : The combination of Silent Word Generation and ≥1 visual semantic paradigm , such as Sentence Completion and Noun-Verb Association , is adequate to determine language localization and lateralization ; Noun-Verb Association has the additional advantage of objective monitoring of patient performance Over 90 % of people activate the left hemisphere more than the right hemisphere for language processing . Here , we show that the degree to which language is left lateralized is inversely related to the degree to which left frontal regions drive activity in homotopic right frontal regions . Lateralization was assessed in 60 subjects using functional magnetic resonance imaging ( fMRI ) activation for semantic decisions on verbal ( written words ) and nonverbal ( pictures of objects ) stimuli . Regional interactions between left and right ventral and dorsal frontal regions were assessed using dynamic causal modeling ( DCM ) , r and om-effects Bayesian model selection at the family level , and Bayesian model averaging at the connection level . We found that 1 ) semantic decisions on words and pictures modulated interhemispheric coupling between the left and right dorsal frontal regions , 2 ) activation was more left lateralized for words than pictures , and 3 ) for words only , left lateralization was greater when the coupling from the left to right dorsal frontal cortex was reduced . These results have theoretical implication s for underst and ing how left and right hemispheres communicate with one another during the processing of lateralized functions BACKGROUND AND PURPOSE : Brain tumors affecting language -relevant areas may influence language lateralization . The purpose of this study was to systematic ally investigate language lateralization in brain tumor patients using clinical language fMRI , comparing the results with a group of healthy volunteers . MATERIAL S AND METHODS : Fifty-seven strictly right-h and ed patients with left-hemispheric-space intracranial masses ( mainly neoplastic ) affecting either the Broca area ( n = 19 ) or Wernicke area ( n = 38 ) were prospect ively enrolled in this study . Fourteen healthy volunteers served as a control group . St and ardized clinical language fMRI , using visually triggered sentence- and word-generation paradigms , was performed on a 1.5 T MR scanner . Semiautomated analyses of all functional data were conducted on an individual basis using BrainVoyager . A regional lateralization index was calculated for Broca and Wernicke areas separately versus their corresponding right-hemisphere homologs . RESULTS : In masses affecting the Broca area , a significant decrease in the lateralization index was found when performing word generation ( P = .0017 ) , whereas when applying sentence generation , the decrease did not reach statistical significance ( P = .851 ) . Masses affecting the Wernicke area induced a significant decrease of the lateralization index when performing sentence generation ( P = .0007 ) , whereas when applying word generation , the decrease was not statistically significant ( P = .310 ) . CONCLUSIONS : Clinical language fMRI was feasible for patients with brain tumors and provided relevant presurgical information by localizing essential language areas and determining language dominance . A significant effect of the brain masses on language lateralization was observed , with a shift toward the contralesional , nondominant hemisphere . This may reflect compensatory mechanisms of the brain to maintain communicative abilities Background Functional magnetic resonance imaging ( fMRI ) continues to develop as a clinical tool for patients with brain cancer , offering data that may directly influence surgical decisions . Unfortunately , routine integration of preoperative fMRI has been limited by concerns about reliability . Many pertinent studies have been undertaken involving healthy controls , but work involving brain tumor patients has been limited . To develop fMRI fully as a clinical tool , it will be critical to examine these reliability issues among patients with brain tumors . The present work is the first to extensively characterize differences in activation map quality between brain tumor patients and healthy controls , including the effects of tumor grade and the chosen behavioral testing paradigm on reliability outcomes . Method Test-retest data were collected for a group of low- grade ( n = 6 ) and high- grade glioma ( n = 6 ) patients , and for matched healthy controls ( n = 12 ) , who performed motor and language tasks during a single fMRI session . Reliability was characterized by the spatial overlap and displacement of brain activity clusters , BOLD signal stability , and the laterality index . Significance testing was performed to assess differences in reliability between the patients and controls , and low- grade and high- grade patients ; as well as between different fMRI testing paradigms . Results There were few significant differences in fMRI reliability measures between patients and controls . Reliability was significantly lower when comparing high- grade tumor patients to controls , or to low- grade tumor patients . The motor task produced more reliable activation patterns than the language tasks , as did the rhyming task in comparison to the phonemic fluency task . Conclusion In low- grade glioma patients , fMRI data are as reliable as healthy control subjects . For high- grade glioma patients , further investigation is required to determine the underlying causes of reduced reliability . To maximize reliability outcomes , testing paradigms should be carefully selected to generate robust activation patterns The aim of this work was to determine whether productive and perceptive language functions are differentially affected in homogeneous groups of epilepsy patients with right and left temporal lobe epilepsy ( TLE ) . Eighteen patients with left TLE , 18 with right TLE , and 17 healthy volunteers were studied using fMRI during performance of three tasks assessing the productive and perceptive aspects of language ( covert semantic verbal fluency , covert sentence repetition , and story listening ) . Hemispheric dominance for language was calculated in the frontal and temporal regions using laterality indices ( LI ) . Atypical lateralization was defined as a right-sided LI ( LI<-0.20 ) in the frontal lobes during the verbal fluency task or in the temporal lobes during the story listening task . Control subjects and right TLE patients demonstrated a strong left lateralization for language in the frontal lobes during the fluency task , whereas activation was less lateralized to the left hemisphere in left TLE patients , although the difference did not reach significance . In the story listening and the repetition tasks , activation was significantly more right sided in the temporal lobes of patients with left TLE . Atypical language representation was found in 19 % of TLE patients ( five left and two right TLE ) . The shift toward the right hemisphere was significantly larger in the temporal than the frontal lobes in patients with atypical language lateralization compared to TLE patients with a typical language lateralization . Neuropsychological performances of patients with atypical language patterns were better than those of patients with typical patterns , suggesting that this reorganization may represent a compensatory mechanism Atypical , right-hemisphere language dominance is poorly understood . It is often observed in patients with brain reorganization due to lesions early in life . It can also be encountered in seemingly normal individuals . We compared the patterns of neural language activation in 7 individuals with left- and 7 with right-hemisphere language dominance , none of whom had any evidence of brain lesions . We speculated that incongruencies in the activation patterns in atypical , right-hemisphere language dominance could indicate a reorganized neural language system after undetected early brain damage . Functional magnetic resonance imaging analysis of brain activation during phonetic word generation demonstrated ( 1 ) . no increased activation in the subdominant hemisphere in right compared to left language dominance , ( 2 ) . a similar variability in the pattern of activation in both groups , and ( 3 ) . a mirror reverse pattern of activation in right- compared to left-hemisphere dominant subjects . These findings support the view that in individuals with an unrevealing medical history right-hemispheric dominance constitutes a natural rather than an abortive variant of language lateralization BACKGROUND AND PURPOSE : Functional MR imaging ( fMRI ) is used to determine preoperatively the laterality of cortical language representation along with the relationship of language areas to adjacent brain tumors . The purpose of this study was to determine whether changing the statistical threshold for different language tasks influences the language laterality index ( LI ) for a group of controls , patients with tumor without prior surgery , and patients with tumor and prior surgery . MATERIAL S AND METHODS : Seven controls , 9 patients with tumor without prior surgery , and 4 patients with tumor and prior surgery performed verb-generation , phonemic fluency , and semantic fluency language tasks during fMRI . Interhemispheric activation differences between the left and right Broca regions of interest were determined by calculating language LIs . LIs were compared within each group , between groups , and between language tasks . Intraoperative electrocortical mapping or the presence of aphasia during postoperative neurology examinations or both were used as ground truth . RESULTS : The language LI varied as a result of statistical thresholding , presence of tumor , prior surgery , and language task . Although patients and controls followed a similar shape in the LI curve , there was no optimal P value for determining the LI . Three patients demonstrated a shift in the LI between hemispheres as a function of statistical threshold . Verb generation was the least variable task both between tasks and across groups . CONCLUSION : For preoperative patients with tumor , the LI should be examined across a spectrum of P values and a range of tasks to ensure reliability . Our data suggest that the LI may be threshold- and task-dependent , particularly in the presence of adjacent tumor RATIONALE AND OBJECTIVES The aim of this study was to assess the intrasubject and intersubject reproducibility of functional magnetic resonance imaging ( fMRI ) language paradigms on language localization and lateralization . MATERIAL S AND METHODS Fourteen healthy volunteers were enrolled prospect ively and underwent language fMRI using visually triggered covert and overt sentence generation ( SG ) and word generation ( WG ) paradigms . Semiautomated analysis of all functional data was performed using Brain Voyager on an individual basis . Regions of interest for Broca 's area , Wernicke 's area , and their contralateral homologues were drawn . The Euclidean coordinates of the center of gravidity ( x , y , and z ) of the respective blood oxygenation level-dependent ( BOLD ) activation cluster , and the correlation of the measured hemodynamic response to the applied reference function ( r ) , relative BOLD signal change as BOLD signal characteristics were measured in each region of interest . Regional lateralization indexes were calculated for Broca 's area , Wernicke 's area , and their contralateral homologues separately . Wilcoxon 's signed-rank test was applied for statistical comparisons ( P values < .05 were considered significant ) . Ten of the 14 volunteers had three repeated measurements to test intrasession reproducibility and intersession reproducibility . RESULTS Overall activation rates for the four paradigms were 89 % for covert SG , 82 % for overt SG , 89 % for covert WG , and 100 % for overt WG . When comparing covert and overt paradigms , language localization was significantly different in 17 % ( Euclidean coordinates ) and 19 % ( BOLD signal characteristics ) , respectively . Language lateralization was significantly different in 75 % . Intrasubject and intersubject reproducibility was excellent , with 3.3 % significant differences among all five parameters for language localization and 0 % significant differences for language lateralization using covert paradigms . CONCLUSIONS Covert language paradigms ( SG and WG ) provided highly robust and reproducible localization and lateralization of essential language centers for scans performed on the same and different days . Their overt counterparts achieved confirmatory localization but lower lateralization capabilities . Reference data for presurgical application are provided Output:	Recommendations are made with a view to informing future research to increase st and ardisation in fMRI laterality protocol s. In particular , the findings reinforce the importance of threshold-independent methods for calculating laterality indices , and the benefits of assessing heterogeneity of language laterality across multiple regions of interest and tasks .
MS21845	*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: IMPORTANCE Panretinal photocoagulation ( PRP ) is the st and ard treatment for reducing severe visual loss from proliferative diabetic retinopathy . However , PRP can damage the retina , result ing in peripheral vision loss or worsening diabetic macular edema ( DME ) . OBJECTIVE To evaluate the noninferiority of intravitreous ranibizumab compared with PRP for visual acuity outcomes in patients with proliferative diabetic retinopathy . DESIGN , SETTING , AND PARTICIPANTS R and omized clinical trial conducted at 55 US sites among 305 adults with proliferative diabetic retinopathy enrolled between February and December 2012 ( mean age , 52 years ; 44 % female ; 52 % white ) . Both eyes were enrolled for 89 participants ( 1 eye to each study group ) , with a total of 394 study eyes . The final 2-year visit was completed in January 2015 . INTERVENTIONS Individual eyes were r and omly assigned to receive PRP treatment , completed in 1 to 3 visits ( n = 203 eyes ) , or ranibizumab , 0.5 mg , by intravitreous injection at baseline and as frequently as every 4 weeks based on a structured re-treatment protocol ( n = 191 eyes ) . Eyes in both treatment groups could receive ranibizumab for DME . MAIN OUTCOMES AND MEASURES The primary outcome was mean visual acuity change at 2 years ( 5-letter noninferiority margin ; intention-to-treat analysis ) . Secondary outcomes included visual acuity area under the curve , peripheral visual field loss , vitrectomy , DME development , and retinal neovascularization . RESULTS Mean visual acuity letter improvement at 2 years was + 2.8 in the ranibizumab group vs + 0.2 in the PRP group ( difference , + 2.2 ; 95 % CI , -0.5 to + 5.0 ; P < .001 for noninferiority ) . The mean treatment group difference in visual acuity area under the curve over 2 years was + 4.2 ( 95 % CI , + 3.0 to + 5.4 ; P < .001 ) . Mean peripheral visual field sensitivity loss was worse ( -23 dB vs -422 dB ; difference , 372 dB ; 95 % CI , 213 - 531 dB ; P < .001 ) , vitrectomy was more frequent ( 15 % vs 4 % ; difference , 9 % ; 95 % CI , 4%-15 % ; P < .001 ) , and DME development was more frequent ( 28 % vs 9 % ; difference , 19 % ; 95 % CI , 10%-28 % ; P < .001 ) in the PRP group vs the ranibizumab group , respectively . Eyes without active or regressed neovascularization at 2 years were not significantly different ( 35 % in the ranibizumab group vs 30 % in the PRP group ; difference , 3 % ; 95 % CI , -7 % to 12 % ; P = .58 ) . One eye in the ranibizumab group developed endophthalmitis . No significant differences between groups in rates of major cardiovascular events were identified . CONCLUSIONS AND RELEVANCE Among eyes with proliferative diabetic retinopathy , treatment with ranibizumab result ed in visual acuity that was noninferior to ( not worse than ) PRP treatment at 2 years . Although longer-term follow-up is needed , ranibizumab may be a reasonable treatment alternative , at least through 2 years , for patients with proliferative diabetic retinopathy . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01489189 Aims The aims were to compare a novel conjunctival mould used to assist the delivery of intravitreal drugs to a conventional technique with respect to patient , surgeon and cost benefit . Methods A prospect i ve review of 200 intravitreal injections was undertaken , 100 using a ‘ conventional ’ freeh and technique ( group 1 ) and 100 using a novel conjunctival mould ( group 2 ) . Intraoperative visual analogue scale ( VAS ) pain scores , patient preference , surgeon perception of the ease of insertion of the conjunctival mould were recorded as well as a cost comparison . Results VAS pain score in the conventional group was 2.58 compared to 1.38 in the conjunctival mould group ( p<0.01 ) . The surgeon reported the insertion of the conjunctival mould as easy in 89 cases , moderate in 10 cases , and difficult in one case . The cost saving with a conjunctival mould pack compared to a conventional pack was £ 7.70 ; an annual saving of £ 19 250 for the trust . Conclusions The reduction in the VAS pain score with the conjunctival mould was statistically significant ( p<0.01 ) . The surgeons found that the device , which was easy to insert , offered excellent globe stability and a safe , reproducible entry site and angle of needle insertion Background The dramatic increase in need for anti-vascular endothelial growth factor ( anti-VEGF ) intravitreal therapy in the treatment of retinal disease and the absence of an equivalent increase in ophthalmologists to undertake such intravitreal injections created a patient-safety risk . Timing of intravitreal therapy ( IVT ) is critical to prevent vision loss and local clinics lacked capacity to treat patients appropriately . We aim ed to improve capacity for IVT by nurse injections . Material s and methods A multidisciplinary prospect i ve service-improvement process was undertaken at two adjacent general hospitals in the northwest of Engl and . IVT injections by nurses were a principal component of solution development . After we had obtained appropriate institutional approval , experienced ophthalmic nurses were trained , supervised , and assessed to undertake IVT . Ophthalmologists directly supervised the first 200 injections , and a retina specialist was always on site . Results Nurses undertook 3,355 intravitreal injections between June 2012 and November 2013 , with minor adverse events ( 0.3 % subconjunctival hemorrhage and corneal abrasion ) . There were no patient complaints at either hospital . Conclusion Experienced ophthalmic nurses quickly learned how to perform such injections safely . IVT by nurses was well accepted by patients and staff . Hospital A trained three nurses sequentially for improved flexibility in scheduling . Novel use of appropriately trained non-medical staff can improve efficiency and access in an overburdened service with time-sensitive disease . Retinal assessment was undertaken by ophthalmologists only . Improved access to IVT is important , as treatment with anti-VEGF therapy reduces blindness at population levels Objectives To investigate the relationship between foveal morphology and self-perceived visual function in patients with neovascular age-related macular degeneration ( AMD ) and whether foveal characteristics are associated with Ranibizumab treatment response on the self-perceived visual function . Methods This prospect i ve cohort study included patients with newly diagnosed neovascular AMD found eligible for treatment with Ranibizumab . Foveal morphology of both eyes was assessed using spectral-domain optical coherence tomography and all patients were interviewed using the 39-item National Eye Institute Visual Function Question naire ( VFQ ) . Patients were re-interviewed 3 and 12 months after initiation of treatment with Ranibizumab . We evaluated foveal morphology at baseline in relation to VFQ scores at baseline and clinical ly meaningful changes in VFQ after 3 and 12 months . Results VFQ scores correlated with central foveal thickness , central foveal thickness of neuroretina ( CFN ) , foveal RPE elevation , foveal integrity of the photoreceptor inner segment/outer segment junction ( IS/OS ) , and external limiting membrane . In a multiple linear regression model , only best-corrected visual acuity of the better eye ( p<0.001 ) and the IS/OS status in the better eye ( p = 0.012 ) remained significant ( Adjusted R2 = 0.418 ) . Lower baseline VFQ and a baseline CFN within 170–270 µm in the better eye were both associated with a clinical ly meaningful increase in the VFQ scores after 3 and 12 months . An absent foveal IS/OS b and in the better eye was associated with a clinical ly meaningful decrease in the VFQ scores at 12 months . Conclusions Foveal morphology in the better eye influences the self-perceived visual function in patients with neovascular AMD and possesses a predictive value for change in the self-perceived visual function at 3 and 12 months after initiation of treatment . These findings may help clinicians provide patients more individualized information of their disease and treatment prognosis from a patient-perceived point-of-view Background Complicated approval procedures and limited short-term surgical capacities can result in time delays between the definition of a medical indication for ranibizumab treatment in active neovascular age-related macular degeneration ( AMD ) and the starting of treatment . This study aim ed to evaluate changes in visual acuity and central retinal thickness over time , and their consequences for the patients concerned . Methods Sixty-nine patients indicated for first-time ranibizumab treatment and 21 patients with necessary re-treatment were included in the study . Visual acuity and spectral domain optical coherence tomography ( SD-OCT ) central retinal thickness at the time of the indication examination were compared to values at the first-time treatment and during recurrent ranibizumab treatment . Results For first-time treatment , the delay between indication and treatment was significantly higher for patients with vision loss compared to those without vision loss ( 31.6 ± 20.5 vs. 24.0 ± 8.3 days , p = 0.012 ) . The increase in OCT central retinal thickness was 50.4 ± 92.8 μm for patients with vision loss compared to 5.1 ± 63.4 μm for those without vision loss , p = 0.029 . A 1.1 logMAR line difference in vision loss was significant at p = 0.01 for patients with a delay in treatment of less than or equal to 28 days ( 48/69 patients , 69.7 % ) compared to those with a delay of more than 28 days ( 21/69 patients , 30.3 % ) . Conclusions Even though average visual decay was slow at about one logMAR line over 110 days , individual patients ( 8.7 % ) experienced rapid loss of one or more lines within 21 days . Administrative procedures should therefore be expedited so that delays do not exceed 2 weeks for the sake of vision preservation in individual patients Purpose A recently developed ranibizumab prefilled syringe ( PFS ) eliminates several preparatory steps versus the st and ard vial-based method , and is expected to reduce syringe preparation time ( SPT ) and enhance procedural simplicity for intravitreal injections . Methods Syringe preparation times for the ranibizumab PFS and vial were recorded during st and ard treatment sessions at 2 centers , without r and omization . The duration of each step in preparing the syringe was recorded . At each center , total SPT ( mean total duration of all syringe preparation steps ) for each method was compared using a 2-tailed t test . Results In total , 97 SPTs were analyzed across both centers . Center 1 SPTs were 46 seconds ( PFS ) versus 75 seconds ( vial ; difference , 29 seconds ; p<0.001 ) . Center 2 SPTs were 46 seconds ( PFS ) versus 63 seconds ( vial ; difference , 17 seconds ; p<0.001 ) . This equates to a 27%-39 % reduction in SPT when using the PFS rather than the vial , result ing mostly from the reduced number of syringe preparation steps associated with the PFS . Conclusions Syringe preparation times for ranibizumab intravitreal injections are significantly shorter with the PFS than with the vial . The time saved by using the PFS may benefit physicians and nurses , and the simplicity of the injection preparation process with the PFS is advantageous PURPOSE To evaluate the prevalence and causes of visual impairment in an epidemiologic study of aged , urban individuals in Denmark . DESIGN Cross-sectional study . PARTICIPANTS The study population consisted of 1000 r and omly selected residents aged 60 to 80 years in Copenhagen , Denmark . Of 976 eligible persons , 946 ( 96.9 % ) could be examined . Information about best-corrected visual acuity ( VA ) was obtained from 944 cooperative persons ( 96.7 % ) . METHODS Data from the Copenhagen City Eye Study were used to assess the cause-specific prevalence of visual impairment as defined by the World Health Organization ( WHO ) ( VA worse than 20/60 - 20/400 in the better eye ) and the criteria used most commonly in the United States ( VA worse than 20/40 but better than 20/200 in the better eye ) . Eligible subjects underwent an extensive ophthalmologic examination at The National University Hospital of Denmark . MAIN OUTCOME MEASURES Best-corrected VA and primary causes of visual impairment . RESULTS The prevalence of low vision according to the WHO definition ranged from 2.6 % in subjects aged 70 to 74 years to 4.8 % in subjects 75 to 80 years of age , with an age-adjusted relative prevalence of 1.58 % . Using the U.S. definition , the Output:	Non-physician delivered intravitreal therapy seems feasible and safe
MS21846	*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 This study evaluated the prognostic role of vascular epidermal growth factor ( VEGF ) , thymidylate synthase ( TS ) , topoisomerase I ( Topo-I ) , topoisomerase IIalpha ( Topo-IIalpha ) and E-cadherin ( E-cadh ) tumor expression , in patients with resectable gastric cancer , who were treated postoperatively with the docetaxel/irinotecan combination . PATIENTS AND METHODS Forty-five patients with resectable gastric cancer were treated with 6 cycles of docetaxel 30 mg/m2 and irinotecan 110 m/m2 on day 1 and d8 every 21 days . All specimens were examined by using immunohistochemistry ( IHC ) for the expression of VEGF , TS , Topo-I , Topo-IIalpha and E-cadh . RESULTS Positivity for TS was significantly correlated with age and for VEGF with diffuse histological type and good PS . No significant correlation was observed among Topo-I , Topo-IIalpha and E-cadh positivity with any of the clinicopathological parameters studied . Median overall survival ( OS ) was 31.7 , and disease-free survival ( DFS ) 26 months , respectively . None of the above-investigated molecular markers were significantly associated with OS and DFS . Finally , according to the univariate analysis for survival , only advanced stages ( III , IV ) of the disease implied risk of death , mainly due to lymph node involvement and , to a lesser extent , tumor size . None of the studied molecular markers were found to be independent prognostic markers . CONCLUSION These results should be interpreted very cautiously , due to the limited number of patients studied , as well as the limitations of the IHC technique Objective To evaluate the correlation between serum vascular endothelial growth factor ( VEGF ) level and the clinicopathologic features in patients with hepatocellular carcinoma ( HCC ) . Summary Background Data VEGF is an important angiogenic factor regulating tumor angiogenesis . A high serum VEGF level has been shown to be associated with tumor progression and metastasis in several human cancers , but its significance in HCC is unclear . The correlation between serum VEGF level and tumor pathologic features in patients with HCC has not been studied before . Methods Preoperative serum sample s and tumor specimens were prospect ively collected in 100 patients undergoing resection of HCC . Serum VEGF level was measured by enzyme-linked immunosorbent assay , and tumor VEGF expression was assessed by immunohistochemical study . Histopathologic examination was performed by a pathologist without prior knowledge of the serum VEGF level or tumor VEGF expression . Results Preoperative serum VEGF levels ranged from 15 to 1,789 pg/mL ( median 269 ) . When serum VEGF levels were compared between groups categorized by different clinicopathologic variables , significant correlation was found between a high serum VEGF level and absence of tumor capsule , presence of intrahepatic metastasis , presence of microscopic venous invasion , and advanced stage . There was a positive correlation between the serum VEGF level and tumor expression of VEGF as well as platelet count . When the 75th percentile serum VEGF level ( 500 pg/mL ) was used as a cutoff level , the frequency of venous invasion in patients with a high serum VEGF level was significantly greater compared with patients with a low serum VEGF level . By multivariate analysis , a serum VEGF level of more than 500 pg/mL and tumor size more than 5 cm were independent preoperative factors predictive of microscopic venous invasion . During a median follow-up of 11.6 months , 48 % of patients with a serum VEGF level of more than 500 pg/mL and 27 % of those with a serum VEGF level of 500 pg/mL or less developed postoperative recurrence . Conclusions These results show that a high preoperative serum VEGF level is a predictor of microscopic venous invasion in HCC , suggesting that the serum VEGF level may be useful as a biologic marker of tumor invasiveness and a prognostic factor in HCC Vascular endothelial growth factor ( VEGF ) is an important regulator of angiogenesis and vascular permeability . Increased serum VEGF concentrations ( S-VEGF ) have been found in patients with various types of human cancer , including cancer of the lung . However , the clinical and prognostic significance of S-VEGF in cancer is unknown . We measured S-VEGF , using enzyme-linked immunosorbent assay , in sera taken from 68 untreated patients with small-cell lung cancer ( SCLC ) at the time of diagnosis . The patients were treated with 6 cycles of cisplatin and etoposide , and were r and omly assigned to receive recombinant interferon , leukocyte interferon or neither . S-VEGF ranged from 70 to 1738 pg/ml ( mean , 527 pg/ml ) . The patients who achieved partial or complete response to treatment had lower pre-treatment S-VEGF than the non-responding patients ( p = 0.0083 , Mann-Whitney test ) . High ( > 527 pg/ml ) S-VEGF was associated with poor survival ( p = 0.012 , Log Rank Test ) , and all 3-year survivors had lower than mean pre-treatment S-VEGF . In a multivariate analysis , S-VEGF and stage were the only independent prognostic factors , and the estimated 3-year survival of the patients with limited stage disease and low pretreatment S-VEGF ( n = 17 , 25 % of all patients ) was 41 % ( p = 0.0055 , log rank test ) . These data show that high pretreatment S-VEGF is associated with poor response to treatment and unfavourable survival in patients with SCLC treated with combination chemotherapy with or without interferon Despite years of research and hundreds of reports on tumor markers in oncology , the number of markers that have emerged as clinical ly useful is pitifully small . Often initially reported studies of a marker show great promise , but subsequent studies on the same or related markers yield inconsistent conclusions or st and in direct contradiction to the promising results . It is imperative that we attempt to underst and the reasons why multiple studies of the same marker lead to differing conclusions . A variety of method ological problems have been cited to explain these discrepancies . Unfortunately , many tumor marker studies have not been reported in a rigorous fashion , and published articles often lack sufficient information to allow adequate assessment of the quality of the study or the generalizability of study results . The development of guidelines for the reporting of tumor marker studies was a major recommendation of the National Cancer Institute – European Organisation for Research and Treatment of Cancer ( NCI – EORTC ) First International Meeting on Cancer Diagnostics in 2000 . As for the successful CONSORT initiative for r and omized trials and for the STARD statement for diagnostic studies , we suggest guidelines to provide relevant information about the study design , preplanned hypotheses , patient and specimen characteristics , assay methods , and statistical analysis methods . In addition , the guidelines provide helpful suggestions on how to present data and important elements to include in discussion s. The goal of these guidelines is to encourage transparent and complete reporting so that the relevant information will be available to others to help them to judge the usefulness of the data and underst and the context in which the conclusions apply Output:	Positive expression of tissue VEGF , circulating VEGF , VEGF-C and VEGF-D were all associated with poor prognosis in resected gastric cancer . However , VEGF demonstrated no significant prognostic value for non-Asian population s. Circulating VEGF may be better than tissue VEGF in predicting prognosis
MS21847	*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 out patients on chronic haemodialysis with polymethylmethacrylate ( PMMA ) membrane dialyzer were r and omly chosen . A control group of 100 likewise r and omly chosen out patients were treated with cuprophane membrane dialyzer . In both groups the treatments lasted for one year . Comparison of the test results revealed that Si , Al and β2M.G levels could be reduced in patients on chronic HD with PMMA This biocompatibility of the new cellulosic membrane hemophane ( HE ) is compared to that of cuprophane ( CU ) in ten maintenance hemodialysis ( HD ) patients dialyzed on the two types of membranes in r and omized order , under otherwise similar technical conditions . Total white blood cell ( WBC ) and differential counts , blood concentrations of C3a , and C3d and histamine are determined at start of dialysis ( TO ) and 10 , 20 and 180 minutes thereafter . HE is distinct from CU in exerting a minor effect on the generation of C3a , a minor drop of leucocytes during the course of dialysis ( P less than 0.01 ) and also by a lesser increase in blood histamine concentration ( P less than 0.05 ) . Histamine liberation is observed on CU together with the generation of anaphylotoxin C3 and with a diminution of circulating basopolymorpho-nuclear cells . According to the variations observed for these three parameters ( C3a , leucocytosis and blood histamine concentration ) , HE appears as being more biocompatible than CU There is increasing evidence that the biochemical and cellular phenomena induced by blood/ membrane/dialysate interactions contribute to dialysis-related intradialytic and long-term complications . However , there is a lack of large , prospect i ve , r and omized trials comparing biocompatible and bioincompatible membranes , and convective and diffusive treatment modalities . The primary aim of this prospect i ve , r and omized trial was to evaluate whether the use of polysulfone membrane with bicarbonate dialysate offers any advantage ( in terms of treatment tolerance , nutritional parameters and pre-treatment beta-microglobulin levels ) over a traditional membrane ( Cuprophan ) . A secondary aim was to assess whether the use of more sophisticated methods consisting of a biocompatible synthetic membrane with different hydraulic permeability at different ultrafiltration rate ( high-flux hemodialysis and hemodiafiltration ) offers any further advantages . Seventy-one Centers were involved and stratified according to the availability of only the first two or all four of the following techniques : Cuprophan hemodialysis ( Cu-HD ) , low-flux polysulfone hemodialysis ( LfPS-HD ) , high-flux polysulfone high-flux hemodialysis ( HfPS-HD ) , and high-flux polysulfone hemodiafiltration ( HfPS-HDF ) . The 380 eligible patients were r and omized to one of the two or four treatments ( 132 to Cu-HD , 147 to LfPS-HD , 51 to HfPS-HD and 50 to HfPS-HDF ) . The follow-up was 24 months . No statistical difference was observed in the algebraic sum of the end points between bicarbonate dialysis with Cuprophan or with low-flux polysulfone , or among the four dialysis methods under evaluation . There was a significant decrease in pre-dialysis plasma beta 2-microglobulin levels in high-flux dialysis of 9.04 + /- 10.46 mg/liter ( 23 % ) and in hemodiafiltration of 6.35 + /- 12.28 mg/liter ( 16 % ) , both using high-flux polysulfone membrane in comparison with Cuprophan and low-flux polysulfone membranes ( P = 0.032 ) . The significant decrease in pre-dialysis plasma beta 2-microglobulin levels could have a clinical impact when one considers that beta 2-microglobulin accumulation and amyloidosis are important long-term dialysis-related complications BACKGROUND Hyperhomocysteinaemia is a putative risk factor for atherothrombotic cardiovascular disease in the haemodialysis population . High-dose vitamin B therapy does not entirely normalize elevated plasma total homocysteine ( tHcy ) levels in haemodialysis patients . Alternative therapies to reduce tHcy further are therefore required . Modifications of the dialysis regimen may result in a better removal of Hcy . We examined the effect of dialyser membrane pore size on tHcy levels in vitamin-replete chronic haemodialysis patients . METHODS Forty-five haemodialysis patients were dialysed during 4 weeks with a low-flux , a high-flux and a super-flux membrane , in r and om order . Pre-dialysis tHcy was determined at baseline and every 4 weeks . In 18 patients , plasma tHcy before and after dialysis and dialysate tHcy concentrations were measured . RESULTS Pre-dialysis tHcy decreased significantly during 4 weeks super-flux dialysis ( -14.6 + /- 2.8 % ) , whereas it remained stable during high-flux ( + 0.5 + /- 2.4 % ) and low-flux dialysis ( + 1.7 + /- 3.2 % ) . The homocysteine reduction ratio was not different for the three membranes : 0.39 + /- 0.03 for the super-flux , 0.47 + /- 0.02 for the high-flux and 0.39 + /- 0.02 for the low-flux dialyser . The amount of Hcy recovered in the dialysate during a single dialysis session was also similar : 117.5 + /- 3.6 micro mol during super-flux , 95.3 + /- 11.5 micro mol during high-flux and 116.5 + /- 11.6 micro mol during low-flux dialysis . CONCLUSION Super-flux dialysis significantly lowers tHcy in chronic haemodialysis patients . Improved removal of middle-molecule uraemic toxins with inhibitory effects on Hcy-metabolizing enzymes , rather than better dialytic clearance of Hcy itself , may explain the beneficial effect of the super-flux membrane Pruritus is one of the major unsolved problems for patients receiving regular hemodialysis . In this study , we conducted a 6 month prospect i ve and crossover trial to investigate the effect of polymethylmethacrylate ( PMMA ) membrane for renal itching . We also examined the role of the tumor necrosis factor (TNF)-alpha system for pruritus in hemodialysis patients . We assessed the degree of skin itching and measured circulating levels of TNF-alpha and soluble TNF receptors ( sTNFR-I , sTNFR-II ) in 19 patients using hemodialysis , complicated by prolonged severe pruritus for 6 months . Serum sTNFR-I and II levels were significantly elevated in hemodialysis patients compared to normal subjects . Serum sTNFR-II levels were significantly and negatively correlated with serum albumin ( r = -0.602 , p = 0.007 ) . A significant positive relationship was also found between sTNFR-I and erythropoietin dosage ( r = 0.554 , p = 0.016 ) . However , no association was found between the degree of pruritus and circulating sTNFR-I and II values . Skin itching scale was significantly decreased from 2.7 + /- 0.2 to 2.1 + /- 0.3 following the use of PMMA membrane for 3 months ( p < 0.05 ) . In contrast , there was no change in itching scales during 3 months of conventional therapy ( 2.2 + /- 0.3 versus 2.2 + /- 0.3 , p = NS ) . PMMA itself did not affect serum TNF-alpha and sTNFR values as well as conventional dialyzer membranes . These findings suggested that the PMMA dialyzer can improve renal itching not mediated through the modification of the TNF-alpha system A crossover study to compare the effects of seven different dialysers on blood gas conditions during dialysis using acetate-containing dialysate was carried out at five centres in four countries . A significant decrease in pO2 was noted at both 15 and 60 min after the start of dialysis for all dialysers , with the greatest decrease at 60 min . Filtral caused the greatest reduction and F 60 the least change at both 15 and 60 min . These differences were statistically significant according to the ANOVA multiple-range test for variance . pCO2 also declined by 1.0 - 2.7 mmHg at 15 min and by 0.7 - 3.8 mmHg at 60 min . The delta pCO2 was comparable across dialysers and no significant differences were found . Although pH showed no change at 15 min , it was slightly but significantly increased at 60 min across all dialysers compared to predialysis values . There were no statistical differences between dialysers . Calculated blood bicarbonate content significantly decreased at 15 min and recovered at 60 min . Along with the greater decrease in pO2 , a larger loss of total CO2 was noted for Filtral . On the other h and F 60 caused the least change in total CO2 . This difference may be due to membrane characteristics affecting the diffusion coefficient for O2 , CO2 , and bicarbonate . Multifactorial mechanisms are likely to be involved , but reflex hypoventilation and an increase in O2 consumption also contributed to hypoxaemia in this study BACKGROUND Half of the dialysis population suffers from hyperphosphataemia , which is now recognized as a major factor of haemodialysis ( HD ) morbidity and mortality . Current control is focussed on reducing dietary phosphate intake and diminishing absorption using phosphate binders , whereas control and quantification of phosphate removal by HD is undervalued . The aim of this prospect i ve study was to develop a simple , bedside formula to estimate dialytic phosphate removal in stable HD patients . METHODS This was a prospect i ve , r and omized trial . Phosphate and urea elimination were assessed in a representative group of patients at two dialysis centres using r and omly different dialysers ( 1.3 - 2.4 m(2 ) ) . Quantification was performed by partial dialysate collection , concentration measurements in blood and effluent dialysate spot sample s , and Kt/V(urea ) during st and ard high-flux HD . Multiple linear regression analyses were used in 77 % of all data sets to generate an equation to predict phosphate removal . The formula was vali date d in the remaining 23 % of data sets , in the same group of patients using a large capillary filter , and in diabetic patients treated with a small dialyser at different blood flows ( 200 , 250 , and 300 ml/min ) . RESULTS A formula allowing quantification of phosphate removal within one HD session was developed in 18 of 74 patients during 41 treatments ( 137 out of 177 data sets ) and was determined as : M(PO4pred)=0.1 t -17 + 50c(ds60)+11c(b60 ) , where t is treatment time in min , c(ds60 ) and c(b60 ) are phosphate concentrations in dialysate and plasma measured 60 min into HD in mmol/l , and M(PO4pred ) is estimated phosphate removed in mmol . The precision was remarkable ( r(2)=0.92 - 0.94 ) . The comparison of phosphate and Kt/V(urea ) showed a significant association ( r(2)=0.28 ) , albeit with remarkable scatter . CONCLUSIONS We present the first approach to quantify phosphate removal during high-flux HD by a bedside formula . Only 28 % of the variation in phosphate removal was explained by Kt/V(urea ) . It appears that other factors not adequately accounted for by Kt/V(urea ) affect phosphate removal . Therefore , we propose an individual control and quantification of phosphate removal in HD In vitro experiments have related anaphylactoid reactions in patients treated with angiotensin-converting enzyme ( ACE ) inhibitors during dialysis with AN69 membranes to excessive bradykinin generation using this negatively charged dialysis membrane . In the present clinical trial plasma bradykinin levels were followed during the early phase of dialysis in 10 patients , not being treated with ACE inhibitors , using AN69 , cuprophane , and polysulfone membranes . Bradykinin was measured after extraction by radioimmunoassay . During this study one episode of anaphylaxis occurred during dialysis with the AN69 membrane . Blood sample s were collected during the first 5 min of the adverse reaction and showed a more than 100-fold increase in the venous effluent of the AN69 dialyzer ( baseline 40 + /- 3 vs. 4,900 + /- 130 fmol/ml after 5 min ) . Even though none of the patients received ACE inhibitors , there were 4 more asymptomatic individuals who displayed a more than two-fold increase in their plasma bradykinin concentrations in the venous effluent of the AN69 dialyzer . When these patients were treated either with cuprophane or with polysulfone dialyzers , no significant bradykinin formation was detected , nor were there any adverse events . Taken together , these findings show that anaphylactoid reactions Output:	When analysed for change in ss(2 ) microglobulin , a fall was only noted with high-flux membranes . We found no evidence of benefit when synthetic membranes were compared with cellulose/modified cellulose membranes in terms of reduced mortality no reduction in dialysis-related adverse symptoms . Despite the relatively large number of RCTs undertaken in this area none of the included studies reported any measures of quality of life
MS21848	*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 coordination training with and without stochastic resonance ( SR ) stimulation on dynamic postural stability . Design Experimental with repeated measures . Setting Research Laboratory . Participants Thirty subjects with functional ankle instability ( FAI ) and 30 healthy subjects . Interventions Subjects were assigned to a conventional coordination training group , SR stimulation coordination training group , or control group . Training groups performed coordination exercises for 6 weeks . Single leg jump-l and ing tests were performed before training began ( pretest ) , and then once every 2 weeks . Jump-l and ing tests required subjects to l and on a single leg on a force plate and stabilize quickly . Main Outcome Measures Anterior/posterior ( A/P ) and medial/lateral ( M/L ) time-to-stabilization ( TTS ) . Results The FAI group improved their A/P TTS over their pretest by 16 % ( test 2 ) , 22 % ( test 3 ) , and 22 % ( posttest ) . They also improved their M/L TTS over their pretest by 16 % ( test 3 ) and 22 % ( posttest ) . Control groups did not improve their TTS ( P>0.05 ) . SR stimulation did not statistically influence TTS ( P>0.05 ) . Effect sizes ( ES ) , however , for our 3-way interaction analyses for A/P TTS ( ES=0.40 ) and M/L TTS ( ES=0.30 ) suggested that SR stimulation improved the FAI group 's M/L TTS after 2 weeks of training , and improved their A/P TTS and M/L TTS to a greater degree after 4 weeks than coordination training alone . Conclusion Coordination training can improve dynamic postural instabilities associated with FAI . SR stimulation might be an alternative therapy for FAI , as this stimulation might improve dynamic postural stability more quickly and to a greater extent than coordination training without SR stimulation UNLABELLED The efficacy of a 6-week rehabilitation program was evaluated in 100 consecutive patients , age 15 - 42 years , with acute anterior cruciate ligament ( ACL ) injury . Arthroscopy revealed associated lesions in 82 % of the patients . Except for resections on menisci with large and unstable lesions , no surgery was performed . The patients were r and omly assigned to supervised training or self-monitored training after instruction . RESULTS At the 6-week follow-up there was no difference between the groups with regard to pain at rest , pain during walking , or experience of giving-way episodes , Tegner activity level of Lysholm knee score . Only 2 of the 100 patients were observed without joint mobility restriction . The only significant difference between the groups was the improvement of muscle function in men in the supervised training group . CONCLUSION Six weeks ' rehabilitation is too short a time period from original injury to obtain normal mobility and restored knee function Background Training of neuromuscular control has become increasingly important and plays a major role in rehabilitation of subjects with an injury to the anterior cruciate ligament ( ACL ) . Little is known , however , of the influence of this training on knee stiffness during loading . Increased knee stiffness occurs as a loading strategy of ACL-injured subjects and is associated with increased joint contact forces . Increased or altered joint loads contribute to the development of osteoarthritis . The aim of the study was to determine if knee stiffness , defined by changes in knee kinetics and kinematics of gait , step activity and cross-over hop could be reduced through a knee-specific 12-week training programme . Methods A 3-dimensional motion analysis system ( VICON ) and a force plate ( AMTI ) were used to calculate knee kinetics and kinematics before and after 12 weeks of knee-specific training in 12 males recruited from a cohort with ACL injury 16 years earlier . Twelve uninjured males matched for age , sex , BMI and activity level served as a reference group . Self-reported patient-relevant data were obtained by the KOOS question naire . Results There were no significant changes in knee stiffness during gait and step activity after training . For the cross-over hop , increased peak knee flexion during l and ing ( from 44 to 48 degrees , p = 0.031 ) and increased internal knee extensor moment ( 1.28 to 1.55 Nm/kg , p = 0.017 ) were seen after training , indicating reduced knee stiffness . The KOOS sport and recreation score improved from 70 to 77 ( p = 0.005 ) and was significantly correlated with the changes in knee flexion during l and ing for the cross-over hop ( r = 0.6 , p = 0.039 ) . Conclusion Knee-specific training improved lower extremity kinetics and kinematics , indicating reduced knee stiffness during dem and ing hop activity . Self-reported sport and recreational function correlated positively with the biomechanical changes supporting a clinical importance of the findings . Further studies are needed to confirm these results in women and in other ACL injured population Improvement of ankle proprioception through physiotherapy ( a.k.a . proprioceptive training ) is a widely accepted conservative treatment modality of chronic functional lateral ankle instability . Clinical studies provided controversial data on its proprioceptive effect . Aim of this study was to gain evidence on the efficacy of proprioceptive training on ankle joint position sense . Ten patients ( five males and five females , aged 23.3±5.4 years ) were treated conservatively for chronic lateral ankle instability with a special training programme over 6 weeks . For the assessment of joint position sense we used the slope-box test , first applied and described by Robbins et al. ( Br J Sports Med 29:242–247 , 1995 ) . The test was performed before the start and after the end of the training programme , measuring joint position sense on 11 different slope amplitudes in four directions ( anterior , posterior , lateral and medial ) in r and om order each on both ankles . Comparisons were made between pre- and post-training results as well as versus a control-group of ten healthy athletes . Overall the proprioceptive sensory function of the studied group has improved , but this improvement was not significant in all directions . Only two patients have shown significant improvement of joint position sense in all directions ( mean estimate error improvement : 2.47 ° ) , while conservative treatment was partially successful in five others ( mean estimate error improvement : 0.73 ° ) . The follow-up results of these seven patients were comparable with the values measured in the control-group . Three patients did not show any improvements ( mean estimate error improvement : −0.55 ° ) ( overall difference between improving and non-improving patients : P<0.0001 ) . Mean absolute estimate error profiles of the seven improving patients became similar to the profiles of healthy athletes , while these changes could not be observed in the case of the three non-improving participants . Proprioceptive rehabilitation programme can be an effective method in order to improve impaired joint position sense function . After 6 weeks non-responding patients can be well identified , and considered for other treatment modalities . The determination of the effective length of the programme however needs further evaluation . Still , changes in the proprioceptive sensory function of the ankle plantarflectors indicate the preventive effect of the training programme . Furthermore , our results support the theory of simultaneous function of different mechanoreceptor-systems STUDY DESIGN A nonr and omized 2-group pretest-posttest design . OBJECTIVES To determine the effects of a 4-week balance training program during stance on a single leg . BACKGROUND Individuals who have experienced multiple episodes of inversion ankle sprains often participate in balance training programs . Balance training is performed to treat existing proprioceptive deficits and to restore ankle joint stability , presumably by retraining altered afferent neuromuscular pathways . The effectiveness of such programs on individuals with functionally unstable ankles has yet to be established . METHODS AND MEASURES Prior to and following training , subjects with self-reported functionally unstable ankles ( 5 women and 8 men , mean age = 21.9 + /- 3.1 years ) and nonimpaired subjects ( 6 women and 7 men , mean age = 21.2 + /- 2.5 years ) completed a static balance assessment for both limbs as well as the ankle joint functional assessment tool question naire ( AJFAT ) . The subjects from both groups participated in a unilateral , multilevel , static and dynamic balance training program 3 times a week for 4 weeks . Subjects from the experimental group trained only the involved limb , and the nonimpaired group trained a r and omly selected limb . A stability index ( SI ) was calculated during the balance assessment to indicate the amount of platform motion . Compared to low stability indices , high stability indices indicate greater platform motion during stance and therefore less stability . RESULTS Following training , subjects from both groups demonstrated significant improvements in balance ability . When balance was assessed at a low resistance to platform tilt ( stability level 2 ) , the posttraining scores of both the subjects with unstable ankles ( mean SI = 2.63 + /- 1.92 ) and the nonimpaired subjects ( mean SI = 2.69 + /- 2.32 ) were significantly better than their pretraining scores ( mean SIs = 5.93 + /- 3.65 and 4.67 + /- 3.43 , respectively ) . Assessed at a high resistance to platform tilt ( stability level 6 ) , the posttraining scores of both subjects with unstable ankles ( mean SI = 1.27 + /- 0.66 ) and the nonimpaired subjects ( mean SI = 1.37 + /- 0.66 ) were significantly better than their pretraining scores ( mean SIs = 2.30 + /- 1.88 and 2.04 + /- 1.43 , respectively ) . Additionally , the posttraining AJFAT scores of subjects with unstable ankles ( 25.78 + /- 3.80 ) and the nonimpaired subjects ( 29.15 + /- 5.27 ) were significantly greater than their pretraining scores ( 17.11 + /- 3.44 and 22.92 + /- 5.22 , respectively ) , indicating an overall improvement in perceived ankle joint functional stability . CONCLUSIONS This study suggests that balance training is an effective means of improving joint proprioception and single-leg st and ing ability in subjects with unstable and nonimpaired ankles A bi-directional bicycle pedal that combines proprioceptive training and evertor strengthening has been developed for the treatment of residual instability after ankle sprains . A prospect i ve r and omized study was carried out on 19 subjects with recurrent ankle sprains and positive stress X-ray films . The subjects were r and omized to use either a bi-directional test pedal or a traditional uni-directional bicycle pedal and then completed a 6-week high-intensity training program on a cycle ergometer . Assessment of training intensity level was based on maximum oxygen uptake values , heart rate and lactate concentration in blood at various submaximal workloads . After completion of the training program , the subjects who had used the test pedal increased peak eversion torque at 180 degrees degrees s-1 by 14.2 % ( P = 0.020 ) , reduced figure-of-eight running time by 0.24 s ( P = 0.003 ) , improved single leg stance speed from 72.5 % to the maximum speed of 80 % ( P = 0.005 ) , and improved Karlsson functional score by 5.1 points ( P = 0.005 ) . In the control group , single leg stance improved from 56.1 to 67.8 % ( P = 0.018 ) , but otherwise no significant effects were found . This study indicates that short-term high-intensity training with a bi-directional pedal improves ankle performance and may be an option in the treatment of recurrent ankle sprains Objectives : To examine the effect of six weeks of strength and proprioception training on eversion to inversion isokinetic strength ratios ( E/I ratios ) in subjects with unilateral functional ankle instability . Methods : Thirty eight subjects were r and omly assigned to one of four treatment groups : strength training ( S ) ; proprioception training ( P ) ; strength + proprioception training ( B ) ; control ( C ) . Isokinetic strength was tested before and after training using a Kin Com 125 automatic positioning isokinetic dynamometer . Subtalar joint eversion and inversion motions were tested both concentrically and eccentrically through a range of motion involving 40 ° . All peak torque and average torque values were normalised for body mass . E/I ratios were calculated from average torque and peak torque measures by taking the concentric eversion value and combining it with the eccentric inversion value . Data were analysed using a mixed model analysis of variance with repeated measures on the test factor . Average torque and peak torque E/I ratios at 30 and 120 ° /s were analysed separately . Results : There were no significant differences in average torque and peak torque E/I ratios of the functionally unstable ankle for any of the groups after training compared with before . Conclusions : Six weeks of strength and proprioception training ( either alone or combined ) had no effect on isokinetic measures of strength in subjects with self reported unilateral functional instability . Further studies examining this agonist ( concentric ) to antagonist ( eccentric ) muscle group strength ratio are needed Background and Purpose The purpose of this study was to determine the effect of a 6-month neuromuscular training ( NT ) program versus a traditional strength training ( ST ) program following anterior cruciate ligament ( ACL ) reconstruction . Subjects Seventy-four subjects with ACL reconstruction participated in the study . Methods The study was a r and omized , single-blinded , controlled trial . The NT and ST groups were tested preoperatively and at 3 and 6 months . The main outcome measure was the Cincinnati Knee Score . Secondary outcome measures were visual analog scales ( VASs ) for pain and function , the 36 Output:	PT/NT was effective at increasing functionality as well as at decreasing the incidence of recurrent injuries and " giving way " episodes after ankle sprains and in conservative treatment of anterior cruciate ligament injuries . However , conflicting results or no efficacy of training were reported for static postural control , joint position sense , neuromuscular control , joint laxity , and lower extremity strength . From this review , it can be concluded that proprioceptive and neuromuscular interventions after ankle and knee joint injuries can be effective for the prevention of recurrent injuries and the improvement of joint functionality
MS21849	*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 Urinary tract infections ( UTI ) can cause acute morbidity and may result in severe problems , including hypertension and reduced renal function . Diagnosis of UTI is extremely important since prompt treatment may prevent damage . In the present study we compared the efficacy of oral cefixime to initial intramuscular ceftizoxime followed by cefixime for the treatment of UTI in children . Fifty-four children were studied . They were r and omized to receive either oral cefixime 8 mg/kg/day for 10 days or initial intramuscular ceftizoxime ( Cefızox ) 50 mg/kg twice a day for 2 days followed by oral cefixime for 8 days . Treatment groups were comparable regarding age , sex , clinical , and laboratory findings . Escherichia coli was isolated from 80 % of patients . Repeat urine cultures were sterile within 24 hours in all children . Cure rates were comparable in both groups ( 92 % vs 86 % at the end of treatment ) . No serious adverse effects were observed . We concluded that oral cefixime is a safe and effective alternative treatment OBJECTIVES To compare the efficacy of 3-day vs 10-day treatment with a combination of amoxicillin and clavulanate potassium for children with uncomplicated urinary tract infections and to determine the role of host factors , including vesicoureteral reflux , and of bacterial virulence factors , including adhesins , in treatment outcome . DESIGN R and omized , double-blind , controlled trial . SETTING A pediatric infectious diseases clinic at an urban medical center . PATIENTS Thirty-seven children with uncomplicated urinary tract infections . INTERVENTIONS Treatment with 3 days or 10 days of antibiotics at a dosage of 20 mg/kg per day of amoxicillin and 5 mg/kg per day of clavulanate potassium in three divided doses . MEASUREMENTS AND MAIN RESULTS The success rate for 10-day treatment was 82 % ( 14/17 ) compared with 55 % ( 11/20 ) for 3-day treatment ( P = .09 ) . Among the 35 patients infected with Escherichia coli , all 10 patients infected with adhesin-negative isolates were treated successfully regardless of the duration of treatment , whereas only 14 ( 56 % ) of the 25 infections involving adhesin-positive isolates were clinical ly cured ( P = .015 ) . Two of the three failures in the 10-day treatment group were in patients with reflux . CONCLUSIONS We conclude that 3-day treatment with amoxicillin and clavulanate is insufficient for afebrile childhood urinary tract infections and that both bacterial and host factors affect treatment outcome Background . The st and ard recommendation for treatment of young , febrile children with urinary tract infection has been hospitalization for intravenous antimicrobials . The availability of potent , oral , third-generation cephalosporins as well as interest in cost containment and avoidance of nosocomial risks prompted evaluation of the safety and efficacy of outpatient therapy . Methods . In a multicenter , r and omized clinical trial , we evaluated the efficacy of oral versus initial intravenous therapy in 306 children 1 to 24 months old with fever and urinary tract infection , in terms of short-term clinical outcomes ( sterilization of the urine and defervescence ) and long-term morbidity ( incidence of reinfection and incidence and extent of renal scarring documented at 6 months by99mTc-dimercaptosuccinic acid renal scans ) . Children received either oral cefixime for 14 days ( double dose on day 1 ) or initial intravenous cefotaxime for 3 days followed by oral cefixime for 11 days . Results . Treatment groups were comparable regarding demographic , clinical , and laboratory characteristics . Bacteremia was present in 3.4 % of children treated orally and 5.3 % of children treated intravenously . Of the short-term outcomes , 1 ) repeat urine cultures were sterile within 24 hours in all children , and 2 ) mean time to defervescence was 25 and 24 hours for children treated orally and intravenously , respectively . Of the long-term outcomes , 1 ) symptomatic reinfections occurred in 4.6 % of children treated orally and 7.2 % of children treated intravenously , 2 ) renal scarring at 6 months was noted in 9.8 % children treated orally versus 7.2 % of children treated intravenously , and 3 ) mean extent of scarring was ∼8 % in both treatment groups . Mean costs were at least twofold higher for children treated intravenously ( $ 3577 vs $ 1473 ) compared with those treated orally . Conclusions . Oral cefixime can be recommended as a safe and effective treatment for children with fever and urinary tract infection . Use of cefixime will result in substantial reductions of health care expenditures Objective To compare the efficacy of oral antibiotic treatment alone with treatment started parenterally and completed orally in children with a first episode of acute pyelonephritis . Design Multicentre , r and omised controlled , open labelled , parallel group , non-inferiority trial . Setting 28 paediatric units in north east Italy . Participants 502 children aged 1 month to < 7 years with clinical pyelonephritis . Intervention Oral co-amoxiclav ( 50 mg/kg/day in three doses for 10 days ) or parenteral ceftriaxone ( 50 mg/kg/day in a single parenteral dose ) for three days , followed by oral co-amoxiclav ( 50 mg/kg/day in three divided doses for seven days ) . Main outcomes measures Primary outcome was the rate of renal scarring . Secondary measures of efficacy were time to defervescence ( < 37 � C ) , reduction in inflammatory indices , and percentage with sterile urine after 72 hours . An exploratory subgroup analysis was conducted in the children in whom pyelonephritis was confirmed by dimercaptosuccinic acid ( DMSA ) scintigraphy within 10 days after study entry . Results Intention to treat analysis showed no significant differences between oral ( n=244 ) and parenteral ( n=258 ) treatment , both in the primary outcome ( scarring scintigraphy at 12 months 27/197 ( 13.7 % ) v 36/203 ( 17.7 % ) , difference in risk −4 % , 95 % confidence interval −11.1 % to 3.1 % ) and secondary outcomes ( time to defervescence 36.9 hours ( SD 19.7 ) v 34.3 hours ( SD 20 ) , mean difference 2.6 ( −0.9 to 6.0 ) ; white cell count 9.8 � 109/l ( SD 3.5 ) v 9.5 � 109/l ( SD 3.1 ) , mean difference 0.3 ( −0.3 to 0.9 ) ; percentage with sterile urine 185/186 v 203/204 , risk difference −0.05 % ( −1.5 % to 1.4 % ) ) . Similar results were found in the subgroup of 278 children with confirmed acute pyelonephritis on scintigraphy at study entry . Conclusions Treatment with oral antibiotics is as effective as parenteral then oral treatment in the management of the first episode of clinical pyelonephritis in children . Trial registration Clinical Trials NCT00161330 Urinary tract infection in children is usually treated with orally administered antibiotics for 10 to 14 days . Because of the unreliability of patient compliance with prescribed medications and because single-dose aminoglycoside therapy has been shown to be effective in women with cystitis , we assessed the efficacy of single-dose amikacin for treatment of first episodes of Escherichia coli lower urinary tract infection in girls . Upper and lower urinary tract infections were presumptively differentiated by simple criteria such as clinical symptoms , fever , and erythrocyte sedimentation rate . Fifty-four girls ( ages 1 to 12 years ) with two positive urine cultures ( greater than 10(5 ) CFU/ml E. coli ) were assigned by a table of r and om numbers to receive treatment with either sulfisoxazole 150 mg/kg/day orally for 10 days or a single dose of amikacin 7.5 mg/kg intramuscularly . Six of 23 patients ( 26 % ) in the amikacin group and four of 21 ( 19 % ) in the sulfisoxazole group had at least one positive urine culture within 40 days after completion of therapy . This difference was not statistically significant ( P greater than 0.5 ) . This suggests that a single dose of amikacin is as effective as a 10-day course of sulfisoxazole in the treatment of presumed first lower urinary tract infection in girls . Additional potential advantages of single-dose therapy are fewer side effects and less toxicity , excellent compliance , and reduced potential for selecting resistant organisms 31 patients with a urinary infection were treated with a single oral dose ( 3 g for adults and 100 mg/kg for children ) of amoxycillin ; 23 ( 74 % ) were cured . 20 women and 26 children were then r and omly allocated to either a single dose of amoxycillin of a 5- to 7-day conventional course of the same antibiotic . The results of both treatment regimens were comparable . Single-dose therapy for the treatment of urinary-tract infections was simple , effective and well tolerated . Patients preferred taking their treatment in this manner . Failure of single-dose therapy to eradicate bacteriuria may indicate which patients require subsequent investigations of their urinary tract Objective . To undertake population pharmacokinetic modeling and to determine the safety and efficacy of once daily ( OD ) gentamicin dosing in children with severe urinary tract infections ( UTI ) . Methods . An open , r and omized , controlled trial comparing OD with three times daily ( TD ) gentamicin dosing in hospitalized children ages 1 month to 12 years with UTI . Daily doses ( milligrams per kg per day ) of gentamicin in both groups were 7.5 ( < 5 years old ) , 6.0 ( 5 to 10 years old ) and 4.5 ( > 10 years old ) . Results . There were 179 children enrolled ( 90 OD , 89 TD ) . Baseline clinical characteristics and pathogens were similar , except that circulatory compromise and renal cortical scintigraphic defects were more common in the OD group . Median gentamicin treatment duration s were 3.0 ( OD ) and 2.7 ( TD ) days . Mean peak gentamicin concentrations were 17.3 ( OD ) vs. 6.4 ( TD ) mg/l ; 99 % of peak concentrations were > 7 mg/l in the OD group whereas 16 % of peak concentrations were < 5 mg/l in the TD group . Mean trough concentrations were 0.35 ( OD ) vs. 0.55 ( TD ) mg/l . In the OD group 4 % of trough concentrations were ≥2 mg/l , whereas in the TD group only 0.7 % were ≥2 mg/l . Age or prior elevated peak concentrations did not predict high trough concentrations . Population pharmacokinetic modeling of the data fitted a one-compartment model with first order elimination . There were no clinical or bacteriologic failures . The two disease-related complications were confined to the OD group . No nephro- or ototoxicity was identified . Conclusions . With age-appropriate dosing and measurement of serum trough concentrations before the second dose , OD gentamicin is safe and effective for the treatment of UTI requiring parenteral treatment in children aged 1 month to 12 years The pharmacokinetics of a low dose of sulfadiazine ( SD 4 mg/kg twice a day , loading dose 8 mg/kg ) were studied and acute urinary tract infection in children treated with this reduced dose . The concentrations of active SD in serum and urine were found to exceed those assumed to be sufficient for the treatment of acute urinary tract infections ( 10 x MIC and 100 x MIC against E. coli , respectively ; MIC = minimum inhibitory concentration ) . The urinary concentrations of both acetylated and non-acetylated SD remained lower than those considered to crystallize in the urinary tract . This suggests that renal damage earlier due to SD overdosage can be avoided by using the present administration . No difference was found in treatment results of acute urinary tract infections in children between SD ( 4 mg/kg twice a day ) and fulfafurazole ( SF ; 50 mg/kg four times a day ) . Only infections caused by sulfonamide-sensitive micro-organisms were treated and all cases were cured . No side-effects could be recorded . SD in lower than the usual dosage would appear to be a practical alternative in the treatment of acute urinary tract infections caused by sulfonamide-sensitive micro-organisms in children Forty-nine ambulatory children between 2 - 1/2 and 12 years of age with acute , clinical ly uncomplicated urinary tract infections caused by susceptible organisms were r and omized to receive a single dose of amoxicillin based on weight or a 10-day course of amoxic Output:	There were no significant differences between groups for persistent symptoms , recurrence following treatment , or re-infection following treatment . There was insufficient data to analyse the effect of antibiotics on renal parenchymal damage , compliance , development of resistant organisms or adverse events . Although antibiotic treatment is effective for children with UTI , there are insufficient data to answer the question of which type of antibiotic or which duration is most effective to treat symptomatic lower UTI . This review found that 10-day antibiotic treatment is more likely to eliminate bacteria from the urine than single-dose treatments . No differences were observed for persistent bacteriuria , recurrence or re-infection between short and long-course antibiotics where the antibiotic differed between groups . This data adds to an existing Cochrane review comparing short and long-course treatment of the same antibiotic who also reported no evidence of difference between short and long-course antibiotics
MS21850	*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 Fruit and vegetables is a heterogeneous food group with different content of dietary fiber , vitamins , minerals , carotenoids , and bioactive phytochemicals . Our objective was to examine the relation between specific consumption of fruit and vegetable subgroups and stroke risk in a cohort of Swedish women and men . METHODS AND RESULTS We prospect ively followed 74,961 participants ( 34,670 women and 40,291 men ) who had completed a food frequency question naire in the autumn of 1997 and were free from stroke , coronary heart disease , and cancer at baseline . Diagnoses of stroke in the cohort during follow-up were ascertained from the Swedish Hospital Discharge Registry . A total of 4089 stroke cases , including 3159 cerebral infa rct ions , 435 intracerebral hemorrhages , 148 subarachnoid hemorrhages , and 347 unspecified strokes , were ascertained during 10.2 years of follow-up . The multivariable relative risk ( RR ) of total stroke for the highest vs. lowest category of total fruit and vegetable consumption was 0.87 ( 95 % confidence interval [ CI ] 0.78 - 0.97 ; P for trend = 0.01 ) . The association was confined to individuals without hypertension ( corresponding RR , 0.81 ; 95 % CI , 0.71 - 0.93 ; P for trend = 0.01 ) . Among individual fruits and vegetable subgroups , inverse associations with total stroke were observed for apples/pears ( RR , 0.89 ; 95 % CI , 0.80 - 0.98 ; P for trend = 0.02 ) and green leafy vegetables ( RR , 0.92 ; 95 % CI , 0.81 - 1.04 ; P for trend = 0.03 ) . CONCLUSION This study shows an inverse association of fruit and vegetable consumption with stroke risk . Particularly consumption of apples and pears and green leafy vegetables was inversely associated with stroke Background There is some evidence that the association of fish and marine fatty acids with stroke risk differs between men and women . We investigated the gender-specific associations of habitual intake of the marine fatty acids eicosapentaenoic acid ( EPA ) plus docosahexaenoic acid ( DHA ) and fish on incident stroke in a population -based study in the Netherl and s. Methods We prospect ively followed 20,069 men and women , aged 20–65 years , without cardiovascular diseases at baseline . Habitual diet was assessed with a vali date d 178-item food frequency question naire . Incidence of stroke was assessed through linkage with mortality and morbidity registers . Cox proportional hazards models were used to estimate multivariable-adjusted hazard ratios ( HR ) and 95 % confidence intervals ( 95%CI ) . Results During 8–13 years of follow-up , 221 strokes occurred . In women , an inverse dose-response relation ( P-trend = 0.02 ) was observed between EPA-DHA intake and incident stroke , with an HR of 0.49 ( 95 % CI : 0.27–0.91 ) in the top quartile of EPA-DHA ( median 225 mg/d ) as compared to the bottom quartile ( median 36 mg/d ) . In men , the HR ( 95%CI ) for the top quartile of EPA-DHA intake was 0.87 ( 0.51–1.48 ) ( P-trend = 0.36 ) . Similar results were observed for fish consumption and stroke incidence . Conclusion A higher EPA-DHA and fish intake is related to a lower stroke risk in women , while for men an inverse association could not be demonstrated CONTEXT Although increased intake of grain products has been recommended to prevent cardiovascular disease ( CVD ) , prospect i ve data examining the relation of whole grain intake to risk of ischemic stroke are sparse , especially among women . OBJECTIVE To examine the hypothesis that higher whole grain intake reduces the risk of ischemic stroke in women . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve cohort of 75,521 US women aged 38 to 63 years without previous diagnosis of diabetes mellitus , coronary heart disease , stroke , or other CVDs in 1984 , who completed detailed food frequency question naires ( FFQs ) in 1984 , 1986 , 1990 , and 1994 , and were followed up for 12 years as part of the Nurses ' Health Study . MAIN OUTCOME MEASURE Incidence of ischemic stroke , confirmed by medical records , by quintile of whole grain intake according to FFQ responses . RESULTS During 861,900 person-years of follow-up , 352 confirmed incident cases of ischemic stroke occurred . We observed an inverse association between whole grain intake and ischemic stroke risk . The age-adjusted relative risks ( RRs ) from the lowest to highest quintiles of whole grain intake were 1.00 ( referent ) , 0.68 ( 95 % confidence interval [ CI ] , 0.49 - 0.94 ) , 0.69 ( 95 % CI , 0.51 - 0.95 ) , 0.49 ( 95 % CI , 0.35 - 0.69 ) , and 0.57 ( 95 % CI , 0.42 - 0.78 ; P = .003 for trend ) . Adjustment for smoking modestly attenuated this association ( RR comparing extreme quintiles , 0.64 ; 95 % CI , 0.47 - 0.89 ) . This inverse association remained essentially unchanged with further adjustment for known CVD risk factors , including saturated fat and transfatty acid intake ( multivariate-adjusted RR comparing extreme quintiles , 0.69 ; 95 % CI , 0.50 - 0.98 ) . The inverse relation between whole grain intake and risk of ischemic stroke was also consistently observed among subgroups of women who never smoked , did not drink alcohol , did not exercise regularly , or who did not use postmenopausal hormones . No significant association was observed between total grain intake and risk of ischemic stroke . CONCLUSIONS In this cohort , higher intake of whole grain foods was associated with a lower risk of ischemic stroke among women , independent of known CVD risk factors . These prospect i ve data support the notion that higher intake of whole grains may reduce the risk of ischemic stroke BACKGROUND The evidence supporting recommendations to limit intake of cholesterol rich foods is inconclusive . We aim ed to examine the association between egg consumption and carotid atherosclerosis phenotypes , and the association with clinical vascular events in a prospect i ve , urban , multi-ethnic population . METHODS AND RESULTS The Northern Manhattan Study is a population based cohort to determine stroke incidence , risk factors and prognosis . A sub-cohort of 1429 NOMAS participants with both carotid ultrasounds and comprehensive dietary information was evaluated ( mean ± SD age of participants 65.80 ± 8.80 , 40 % male , 18 % white , 20 % black , 60 % Hispanic ) . The association between egg consumption and carotid intima media thickness ( cIMT ) was assessed with linear regression . Logistic and quantile regression was used to examine the association between egg consumption and carotid plaque presence , thickness , and area . The relation between egg consumption and clinical vascular events ( N = 2669 ) was examined with Cox models . The mean total cIMT was 0.91 ± 0.08 mm and 58 % had carotid plaque present . Increasing egg consumption was inversely associated with cIMT , plaque presence , thickness , and area , in models adjusted for demographics , vascular risk factors and diet . For every additional egg consumed per week , the risk of plaque decreased by 11 % ( 95 % CI 3%-18 % ) . No association was detected between egg consumption and risk of clinical vascular outcomes , over a mean follow up of 11 years and after adjustment for covariates . CONCLUSIONS Frequency of egg consumption in the low to moderate range was inversely related to several markers of carotid atherosclerosis . No association with clinical vascular events , including stroke , was detected . Our findings do not support current vascular health guidelines suggesting the extreme limitation or avoidance of egg consumption due to its cholesterol content BACKGROUND Data on the relation of plasma and dietary omega-3 ( n-3 ) fatty acids ( FAs ) with heart failure ( HF ) risk have been inconsistent . OBJECTIVE We evaluated the relation of n-3 FAs with HF in US male physicians . DESIGN We used nested case-control ( n = 1572 ) and prospect i ve cohort study design s ( n = 19,097 ) . Plasma phospholipid n-3 FAs were measured by using gas chromatography , and food-frequency question naires were used to assess dietary n-3 FAs and fish intake . Incident HF was ascertained via annual follow-up question naires and vali date d in a sub sample . RESULTS The mean age was 58.7 y at blood collection . In a multivariable model , plasma α-linolenic acid ( ALA ) was associated with a lower risk of HF in a nonlinear fashion ( P-quadratic trend = 0.02 ) , and the lowest OR was observed in quintile 4 ( 0.66 ; 95 % CI : 0.47 , 0.94 ) . Plasma EPA and DHA were not associated with HF , whereas plasma docosapentaenoic acid ( DPA ) showed a nonlinear inverse relation with HF for quintile 2 ( OR : 0.55 ; 95 % CI : 0.39 , 0.79 ) . Dietary marine n-3 FAs showed a trend toward a lower risk of HF in quintile 4 ( HR : 0.81 ; 95 % CI : 0.64 , 1.02 ) and a nonlinear pattern across quintiles . Fish intake was associated with a lower risk of HF , with RRs of ~0.70 for all categories of fish consumption greater than one serving per month . CONCLUSIONS Our data are consistent with an inverse and nonlinear relation of plasma phospholipid ALA and DPA , but not EPA or DHA , with HF risk . Fish consumption greater than once per month was associated with a lower HF risk Background — Sugar-sweetened beverage consumption is associated with weight gain and risk of type 2 diabetes mellitus . Few studies have tested for a relationship with coronary heart disease ( CHD ) or intermediate biomarkers . The role of artificially sweetened beverages is also unclear . Methods and Results — We performed an analysis of the Health Professionals Follow-Up Study , a prospect i ve cohort study including 42 883 men . Associations of cumulatively averaged sugar-sweetened ( eg , sodas ) and artificially sweetened ( eg , diet sodas ) beverage intake with incident fatal and nonfatal CHD ( myocardial infa rct ion ) were examined with proportional hazard models . There were 3683 CHD cases over 22 years of follow-up . Participants in the top quartile of sugar-sweetened beverage intake had a 20 % higher relative risk of CHD than those in the bottom quartile ( relative risk=1.20 ; 95 % confidence interval , 1.09–1.33 ; P for trend < 0.01 ) after adjustment for age , smoking , physical activity , alcohol , multivitamins , family history , diet quality , energy intake , body mass index , pre-enrollment weight change , and dieting . Artificially sweetened beverage consumption was not significantly associated with CHD ( multivariate relative risk=1.02 ; 95 % confidence interval , 0.93–1.12 ; P for trend=0.28 ) . Adjustment for self-reported high cholesterol , high triglycerides , high blood pressure , and diagnosed type 2 diabetes mellitus slightly attenuated these associations . Intake of sugar-sweetened but not artificially sweetened beverages was significantly associated with increased plasma triglycerides , C-reactive protein , interleukin-6 , and tumor necrosis factor receptors 1 and 2 and decreased high-density lipoprotein , lipoprotein(a ) , and leptin ( P<0.02 ) . Conclusions — Consumption of sugar-sweetened beverages was associated with increased risk of CHD and some adverse changes in lipids , inflammatory factors , and leptin . Artificially sweetened beverage intake was not associated with CHD risk or biomarkers The authors aim ed to evaluate the association of the traditional Mediterranean diet and major food groups with incidence of and mortality from cerebrovascular disease ( CBVD ) in a Mediterranean population . The study population was a cohort of 23,601 participants from the Greek segment of the EPIC Study ( European Prospect i ve Investigation into Cancer and Nutrition ) who were free of cardiovascular diseases and cancer at baseline ( 1994 - 1999 ) . Diet was assessed by means of a vali date d food frequency question naire . A 10-point scale integrating key Mediterranean diet characteristics was used to assess the participants ' degree of adherence to this diet . During a median follow-up period of 10.6 years ( 1994 - 2009 Output:	There were clear indications for non-linear dose-response relationships between whole grains , fruits , nuts , dairy , and red meat and CHD . Conclusion : An optimal intake of whole grains , vegetables , fruits , nuts , legumes , dairy , fish , red and processed meat , eggs and SSB showed an important lower risk of CHD , stroke , and HF
MS21851	*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 To evaluate long-term survival of the first cohort of stage-4 neuroblastoma patients treated with the N7 induction chemotherapy , surgery of the primary tumor and high-dose chemotherapy ( HDC ) containing Busulfan-Melphalan ( Bu-Mel ) followed by autologous stem cell transplantation ( ASCT ) . PROCEDURE From 1998 to 1999 , 47 children were included in the NB97 trial and treated with induction chemotherapy according to the N7 protocol , followed by surgery of the primary tumor . HDC ( Busulfan , 600 mg/m(2 ) Melphalan , 140 mg/m(2 ) ) was administered in patients with partial response of metastases with no more than 3 mIBG spots . Radiotherapy was delivered to the primary tumor site when tumors displayed MYCN amplification . RESULTS Thirty-nine patients received Bu-Mel ( 83 % ) : 23 who had achieved complete response ( CR ) of metastases , 20 after induction treatment and 3 after second-line chemotherapy , and 16 in partial response ( PR ) . The toxicity of the whole treatment was manageable . The main HDC related-toxicity was hepatic veno-occlusive disease grade > 2 occurring in 15 % of the patients . The 8-year EFS of the whole cohort was 34 % ( 95 % CI , 22 - 48 % ) . The 8-year EFS of the 39 patients who received Bu-Mel and ASCT was 41 % ( 95 % CI , 27 - 57 % ) . Patients who achieved a CR of metastases at the end of induction chemotherapy had a significantly better outcome than the others ( 8-year EFS , 52 % vs. 20 % ; P = 0.02 ) . CONCLUSIONS The long-term results of this first prospect i ve cohort of patients with metastatic disease treated with the N7 induction chemotherapy and HDC ( Bu-Mel ) confirm published data with stable survival curves but with a longer follow-up BACKGROUND Myeloablative megatherapy is commonly used to improve the poor outlook of children with high-risk neuroblastoma , yet its role is poorly defined . We aim ed to assess whether megatherapy with autologous stem-cell transplantation could increase event-free survival and overall survival compared with maintenance chemotherapy . METHODS 295 patients with high-risk neuroblastoma ( ie , patients with stage 4 disease aged older than 1 year or those with MYCN-amplified tumours and stage 1 , 2 , 3 , or 4S disease or stage 4 disease and < 1 year old ) were r and omly assigned to myeloablative megatherapy ( melphalan , etoposide , and carboplatin ) with autologous stem-cell transplantation ( n=149 ) or to oral maintenance chemotherapy with cyclophosphamide ( n=146 ) . The primary endpoint was event-free survival . Secondary endpoints were overall survival and the number of treatment-related deaths . Analyses were done by intent to treat , as treated , and treated as r and omised . FINDINGS Intention-to-treat analysis showed that patients allocated megatherapy had increased 3-year event-free survival compared with those allocated maintenance therapy ( 47 % [ 95 % CI 38 - 55 ] vs 31 % [ 95 % CI 23 - 39 ] ; hazard ratio 1.404 [ 95 % CI 1.048 - 1.881 ] , p=0.0221 ) , but did not have significantly increased 3-year overall survival ( 62 % [ 95 % CI 54 - 70 ] vs 53 % [ 95 % CI 45 - 62 ] ; 1.329 [ 0.958 - 1.843 ] , p=0.0875 ) . Improved 3-year event-free survival and 3-year overall survival were also recorded for patients given megatherapy in the as-treated group ( n=212 ) and in the treated-as-r and omised group ( n=145 ) . Two patients died from therapy-related complications during induction treatment . No patients given maintenance therapy died from acute treatment-related toxic effects . Five patients given megatherapy died from acute complications related to megatherapy . INTERPRETATION Myeloablative chemotherapy with autologous stem-cell transplantation improves the outcome for children with high-risk neuroblastoma despite the raised risk of treatment-associated death BACKGROUND The current st and ard treatment for patients with high-risk neuroblastoma includes initial induction chemotherapy with a 21-day interval between induction treatments . We aim ed to assess whether an intensive chemotherapy protocol that had a 10-day interval between treatments would improve event-free survival ( EFS ) in patients aged 1 year or over with high-risk neuroblastoma . METHODS Between Oct 30 , 1990 , and March 18 , 1999 , patients with stage 4 neuroblastoma who had not received previous chemotherapy were enrolled from 29 centres in Europe . Patients were r and omly assigned to rapid treatment ( cisplatin [ C ] , vincristine [ O ] , carboplatin [ J ] , etoposide [ E ] , and cyclophosphamide [ C ] , known as COJEC ) or st and ard treatment ( vincristine [ O ] , cisplatin [ P ] , etoposide [ E ] , and cyclophosphamide [ C ] , ie , OPEC , alternated with vincristine [ O ] , carboplatin [ J ] , etoposide [ E ] , and cyclophosphamide [ C ] , ie , OJEC ) . Both regimens used the same total cumulative doses of each drug ( except vincristine ) , but the dose intensity of the rapid regimen was 1.8-times higher than that of the st and ard regimen . The st and ard regimen was given every 21 days if patients showed haematological recovery , whereas the rapid regimen was given every 10 days irrespective of haematological recovery . Response to chemotherapy was assessed according to the conventional International Neuroblastoma Response Criteria ( INRC ) . In responders , surgical excision of the primary tumour was attempted , followed by myeloablation ( with 200 mg/m2 of melphalan ) and haemopoietic stem-cell rescue . Primary endpoints were 3-year , 5-year , and 10-year EFS . Data were analysed by intention to treat . This trial is registered on the clinical trials site of the US National Cancer Institute website , number NCT00365755 , and also as EU-20592 and CCLG-NB-1990 - 11 . FINDINGS 262 patients , of median age 2.95 years ( range 1.03 - 20.97 ) , were r and omly assigned-132 patients to st and ard and 130 patients to rapid treatment . 111 patients in the st and ard group and 109 patients in the rapid group completed chemotherapy . Chemotherapy doses were recorded for 123 patients in the st and ard group and 126 patients in the rapid group . 97 of 123 ( 79 % ) patients in the st and ard group and 84 of 126 ( 67 % ) patients in the rapid group received at least 90 % of the scheduled chemotherapy , and the relative dose intensity was 1.94 compared with the st and ard regimen . 3-year EFS was 24.2 % for patients in the st and ard group and 31.0 % for those in the rapid group ( hazard ratio [ HR ] 0.86 [ 95 % CI 0.66 - 1.14 ] , p=0.30 . 5-year EFS was 18.2 % in the st and ard group and 30.2 % in the rapid group , representing a difference of 12.0 % ( 1.8 to 22.3 ) , p=0.022 . 10-year EFS was 18.2 % in the st and ard group and 27.1 % in the rapid group , representing a difference of 8.9 % ( -1.2 to 19.0 ) , p=0.085 . Myeloablation was given a median of 55 days earlier in patients assigned rapid treatment than those assigned st and ard treatment . Infective complications ( numbers of patients with febrile neutropenia and septicaemia , and if given , time on antibiotic and antifungal treatment ) and time in hospital were greater with rapid treatment . Occurrence of fungal infection was the same in both regimens . INTERPRETATION Dose intensity can be increased with a rapid induction regimen in patients with high-risk neuroblastoma . There was no significant difference in OS between the rapid and st and ard regimens at 5 years and 10 years . However , an increasing difference in EFS after 3 years suggests that the efficacy of the rapid regimen is better than the st and ard regimen . A rapid induction regimen enables myeloablation to be given much earlier , which might contribute to a better outcome UNLABELLED PURPOSE We assessed the long-term outcome of patients enrolled on CCG-3891 , a high-risk neuroblastoma study in which patients were r and omly assigned to undergo autologous purged bone marrow transplantation ( ABMT ) or to receive chemotherapy , and subsequent treatment with 13-cis-retinoic acid ( cis-RA ) . PATIENTS AND METHODS Patients received the same induction chemotherapy , with r and om assignment ( N = 379 ) to consolidation with myeloablative chemotherapy , total-body irradiation , and ABMT versus three cycles of intensive chemotherapy . Patients who completed consolidation without disease progression were r and omly assigned to receive no further therapy or cis-RA for 6 months . Results The event-free survival ( EFS ) for patients r and omly assigned to ABMT was significantly higher than those r and omly assigned to chemotherapy ; the 5-year EFS ( mean + /- SE ) was 30 % + /- 4 % versus 19 % + /- 3 % , respectively ( P = .04 ) . The 5-year EFS ( 42 % + /- 5 % v 31 % + /- 5 % ) from the time of second r and om assignment was higher for cis-RA than for no further therapy , though it was not significant . Overall survival ( OS ) was significantly higher for each r and om assignment by a test of the log(-log ( . ) ) transformation of the survival estimates at 5 years ( P < .01 ) . The 5-year OS from the second r and om assignment of patients who underwent both r and om assignments and who were assigned to ABMT/cis-RA was 59 % + /- 8 % ; for ABMT/no cis-RA , it was 41 % + /- 8 % [ corrected ] ; for continuing chemotherapy/cis-RA , it was 38 % + /- 7 % ; and for chemotherapy/no cis-RA , it was 36 % + /- 7 % . CONCLUSION Myeloablative therapy and autologous hematopoietic cell rescue result in significantly better 5-year EFS than nonmyeloablative chemo therapy ; neither myeloablative therapy with [ corrected ] autologous hematopoietic cell rescue nor cis-RA given after consolidation therapy significantly improved OS BACKGROUND The N7 protocol for poor-risk neuroblastoma uses dose-intensive chemotherapy ( as in N6 protocol [ Kushner et al. : J Clin Oncol 12:2607 - 2613 , 1994 ] but with lower dosing of vincristine ) for induction , surgical resection and 2100 cGy hyperfractionated radiotherapy for local control , and for consolidation , targeted radioimmunotherapy with 131I-labeled anti-GD2 3F8 monoclonal antibody and immunotherapy with unlabeled/unmodified 3F8 ( 400 mg/m2 ) . PROCEDURE The chemotherapy consists of : cyclophosphamide 70 mg/kg/d x 2 and a 72-hr infusion of doxorubicin 75 mg/m2 plus vincristine 2 mg/m2 , for courses 1 , 2 , 4 , and 6 ; and cisplatin 50 mg/m2/d x 4 and etoposide 200 mg/m2/d x 3 , for courses 3 , 5 , and 7 . 131I-3F8 is dosed at 20 mCi/kg , which is myeloablative and therefore necessitates stem-cell support . RESULTS Of the first 24 consecutive previously untreated patients more than 1 year old at diagnosis , 22 were stage 4 and two were unresectable stage 3 with MYCN amplification . Chemotherapy achieved CR/VGPR in 21 of 24 patients . Twenty patients to date have completed treatment with 131I-3F8 , and 15 patients have completed all treatment . With a median follow-up of 19 months , 18 of 24 patients remain progression-free . CONCLUSIONS Major toxicities were grade 4 myelosuppression and mucositis during chemotherapy , and self-limited pain and urticaria during antibody treatment . Late effects include hearing deficits and hypothyroidism BACKGROUND Myeloablative chemoradiotherapy and immunomagnetically purged autologous bone marrow transplantation has been shown to improve outcome for patients with high-risk neuroblastoma . Currently , peripheral blood stem cells ( PBSC ) are infused Output:	For febrile neutropenia , septicemia , and renal toxicity , a statistically significant difference in favor of the st and ard treatment arm was identified ; for all other early toxicities no clear evidence of a difference between treatment groups was identified . For endocrine complications and neurocognitive complications , a statistically significant difference in favor of the rapid COJEC arm was found ; for all other late non-hematological toxicities no clear evidence of a difference between treatment groups was identified . Therefore , based on the currently available evidence , we are uncertain about the effects of rapid COJEC and st and ard induction therapy in patients with high-risk neuroblastoma .
MS21852	*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 Adverse drug-related events are common in the elderly , and inappropriate prescribing is a preventable risk factor . Our objective was to determine whether inappropriate prescribing could be reduced when primary care physicians had computer-based access to information on all prescriptions dispensed and automated alerts for potential prescribing problems . METHODS We r and omly assigned 107 primary care physicians with at least 100 patients aged 66 years and older ( total 12 560 ) to a group receiving computerized decision-making support ( CDS ) or a control group . Physicians in the CDS group had access to information on current and past prescriptions through a dedicated computer link to the provincial seniors ' drug-insurance program . When any of 159 clinical ly relevant prescribing problems were identified by the CDS software , the physician received an alert that identified the nature of the problem , possible consequences and alternative therapy . The rate of initiation and discontinuation of potentially inappropriate prescriptions was assessed over a 13-month period . RESULTS In the 2 months before the study , 31.8 % of the patients in the CDS group and 33.3 % of those in the control group had at least 1 potentially inappropriate prescription . During the study the number of new potentially inappropriate prescriptions per 1000 visits was significantly lower ( 18 % ) in the CDS group than in the control group ( relative rate [ RR ] 0.82 , 95 % confidence interval [ CI ] 0.69 - 0.98 ) , but differences between the groups in the rate of discontinuation of potentially inappropriate prescriptions were significant only for therapeutic duplication by the study physician and another physician ( RR 1.66 , 95 % CI 0.99 - 2.79 ) and drug interactions caused by prescriptions written by the study physician ( RR 2.15 , 95 % CI 0.98 - 4.70 ) . INTERPRETATION Computer-based access to complete drug profiles and alerts about potential prescribing problems reduces the rate of initiation of potentially inappropriate prescriptions but has a more selective effect on the discontinuation of such prescriptions OBJECTIVES To evaluate the effect of pharmaceutical care provided in addition to acute Geriatric Evaluation and Management ( GEM ) care on the appropriateness of prescribing . DESIGN R and omized , controlled trial , with the patient as unit of r and omization . SETTING Acute GEM unit . PARTICIPANTS Two hundred three patients aged 70 and older . INTERVENTION Pharmaceutical care provided from admission to discharge by a specialist clinical pharmacist who had direct contacts with the GEM team and patients . MEASUREMENTS Appropriateness of prescribing on admission , at discharge , and 3 months after discharge , using the Medication Appropriateness Index ( MAI ) , Beers criteria , and Assessing Care of Vulnerable Elders ( ACOVE ) underuse criteria and mortality , readmission , and emergency visits up to 12 months after discharge . RESULTS Intervention patients were significantly more likely than control patients to have an improvement in the MAI and in the ACOVE underuse criteria from admission to discharge ( odds ratio (OR)=9.1 , 95 % confidence interval (CI)=4.2 - 21.6 and OR=6.1 , 95 % CI=2.2 - 17.0 , respectively ) . The control and intervention groups had comparable improvements in the Beers criteria . CONCLUSION Pharmaceutical care provided in the context of acute GEM care improved the appropriate use of medicines during the hospital stay and after discharge . This is an important finding , because only limited data exist on the effect of various strategies to improve medication use in elderly in patients . The present approach has the potential to minimize risk and improve patient outcomes OBJECTIVES To determine whether a medication review by a specialized team would promote regimen changes in elders taking multiple medications and to measure the effect of regimen changes on monthly cost and functioning . DESIGN A r and omized-controlled trial . SETTING Health center ambulatory clinic . PARTICIPANTS Community-dwelling older adults taking five or more medications were assessed at baseline and 6 weeks . A medication-change intervention group of 57 elders was compared with a control group of 76 elder adults . INTERVENTION The primary intervention was a comprehensive review and recommended modification of a patient 's medication regimen . Changes were endorsed by each patient 's primary physician and discussed with each patient . MEASUREMENTS Measures were the Timed Manual Performance Test , Physical Performance Test , Functional Reach Assessment , subtests from the Wechsler Adult Intelligence Scale , a modified R and t Memory Test , the Center for Epidemiological Studies -Depression Scale , the Self-Rating Anxiety Scale , and the R and 36-item Health Survey 1.0 . Comorbidity was determined using the International Classification of Diseases , Ninth Revision , Clinical Modification . Medication usage was determined using brown bag review . RESULTS Intervention subjects decreased their medications by an average of 1.5 drugs . No differences in functioning were observed between groups . Intervention subjects saved an average $ 26.92 per month in wholesale medication costs ; control subjects saved $ 6.75 per month ( P<.006 ) . CONCLUSION Although the intervention significantly reduced the medications taken and monthly cost , most patients were resistant to reducing medications to the recommended level . Further study is needed to underst and patient resistance to reducing adverse polypharmacy and to devise better strategies for addressing this important problem in geriatric health . Greater focus on prescriber behavior is recommended OBJECTIVES to evaluate specialist geriatric input and medication review in patients in high-dependency continuing care . DESIGN prospect i ve , r and omised , controlled trial . SETTING two residential continuing care hospitals . PARTICIPANTS two hundred and twenty-five permanent patients . INTERVENTION patients were r and omised to either specialist geriatric input or regular input . The specialist group had a medical assessment by a geriatrician and medication review by a multidisciplinary expert panel . Regular input consisted of review as required by a medical officer attached to each ward . Re assessment occurred after 6 months . RESULTS one hundred and ten patients were r and omised to specialist input and 115 to regular input . These were comparable for age , gender , dependency levels and cognition . After 6 months , the total number of medications per patient per day fell from 11.64 to 11.09 in the specialist group ( P = 0.0364 ) and increased from 11.07 to 11.5 in the regular group ( P = 0.094 ) . There was no significant difference in mortality or frequency of acute hospital transfers ( 11 versus 6 in the specialist versus regular group , P = 0.213 ) . CONCLUSION specialist geriatric assessment and medication review in hospital continuing care result ed in a reduction in medication use , but at a significant cost . No benefits in hard clinical outcomes were demonstrated . However , qualitative benefits and lower costs may become evident over longer periods AIMS This study aims to determine if potentially inappropriate prescribing ( PIP ) is associated with increased healthcare utilization , functional decline and reduced quality of life ( QoL ) in a community-dwelling older cohort . METHOD This prospect i ve cohort study included participants aged ≥65 years from The Irish Longitudinal Study on Ageing ( TILDA ) with linked administrative pharmacy cl aims data who were followed up after 2 years . PIP was defined by the Screening Tool for Older Persons Prescriptions ( STOPP ) and Screening Tool to Alert doctors to Right Treatment ( START ) . The association with number of emergency department ( ED ) visits and GP visits reported over 12 months was analyzed using multivariate negative binomial regression adjusting for confounders . Marginal structural models investigated the presence of time-dependent confounding . RESULTS Of participants followed up ( n = 1753 ) , PIP was detected in 57 % by STOPP and 41.8 % by START , 21.7 % reported an ED visit and 96.1 % visited a GP ( median 4 , IQR 2.5 - 6 ) . Those with any STOPP criterion had higher rates of ED visits ( adjusted incident rate ratio ( IRR ) 1.30 , 95 % confidence interval ( CI ) 1.02 , 1.66 ) and GP visits ( IRR 1.15 , 95%CI 1.06 , 1.24 ) . Patients with two or more START criteria had significantly more ED visits ( IRR 1.45 , 95%CI 1.03 , 2.04 ) and GP visits ( IRR 1.13 , 95%CI 1.01 , 1.27 ) than people with no criteria . Adjusting for time-dependent confounding did not affect the findings . CONCLUSIONS Both STOPP and START were independently associated with increased healthcare utilization and START was also related to functional decline and QoL. Optimizing prescribing to reduce PIP may provide an improvement in patient outcomes BACKGROUND The pharmaceutical care approach serves as a model for medication review , involving collaboration between GPs , pharmacists , patients , and carers . Its use is advocated with older patients who are typically prescribed several drugs . However , it has yet to be thoroughly evaluated . AIM To estimate the effectiveness of pharmaceutical care for older people , shared between GPs and community pharmacists in the UK , relative to usual care . DESIGN OF STUDY Multiple interrupted time-series design in five primary care trusts which implemented pharmaceutical care at 2-month intervals in r and om order . Patients acted as their own controls , and were followed over 3 years including their 12 months ' participation in pharmaceutical care . SETTING In 2002 , 760 patients , aged > or = 75 years , were recruited from 24 general practice s in East and North Yorkshire . Sixty-two community pharmacies also took part . A total of 551 participants completed the study . METHOD Pharmaceutical care was undertaken by community pharmacists who interviewed patients , developed and implemented pharmaceutical care plans together with patients ' GPs , and thereafter undertook monthly medication review s. Pharmacists and GPs attended training before the intervention . Outcome measures were the UK Medication Appropriateness Index , the Short Form-36 Health Survey ( SF-36 ) , and serious adverse events . RESULTS The intervention did not lead to any statistically significant change in the appropriateness of prescribing or health outcomes . Although the mental component of the SF-36 decreased as study participants become older , this trend was not affected by pharmaceutical care . CONCLUSION The RESPECT model of pharmaceutical care ( R and omised Evaluation of Shared Prescribing for Elderly people in the Community over Time ) shared between community pharmacists and GPs did not significantly change the appropriateness of prescribing or quality of life in older patients Abstract Objective : To determine whether a pharmacist can effectively review repeat prescriptions through consultations with elderly patients in general practice . Design : R and omised controlled trial of clinical medication review by a pharmacist against normal general practice review . Setting : Four general practice s. Participants : 1188 patients aged 65 or over who were receiving at least one repeat prescription and living in the community . Intervention : Patients were invited to a consultation at which the pharmacist review ed their medical conditions and current treatment . Main outcome measures : Number of changes to repeat prescriptions over one year , drug costs , and use of healthcare services . Results : 590 ( 97 % ) patients in the intervention group were review ed compared with 233 ( 44 % ) in the control group . Patients seen by the pharmacist were more likely to have changes made to their repeat prescriptions ( mean number of changes per patient 2.2 v 1.9 ; difference=0.31 , 95 % confidence interval 0.06 to 0.57 ; P=0.02 ) . Monthly drug costs rose in both groups over the year , but the rise was less in the intervention group ( mean difference £ 4.72 per 28 days , −£7.04 to -£2.41 ) ; equivalent to £ 61 per patient a year . Intervention patients had a smaller rise in the number of drugs prescribed ( 0.2 v 0.4 ; mean difference −0.2 , −0.4 to −0.1 ) . There was no evidence that review of treatment by the pharmacist affected practice consultation rates , outpatient consultations , hospital admissions , or death rate . Conclusions : A clinical pharmacist can conduct effective consultations with elderly patients in general practice to review their drugs . Such review results in significant changes in patients ' drugs and saves more than the cost of the intervention without affecting the workload of general practitioners . What is already known on this topic Review of patients on long term drug treatment is important but is done inadequately Evidence from the United States shows that pharmacists can improve patient care by review ing drug treatment What this study adds Consultations with a clinical pharmacist are an effective method of review ing the drug treatment of older patients Review by a pharmacist results in more drug changes and lower prescribing costs than normal care plus a much higher review rate Use of healthcare services by patients is not OBJECTIVE Inappropriate drug prescription is a common problem in people living in nursing homes and is linked to adverse health outcomes . This study assessed the effect of an educational intervention directed to nursing home physicians in reducing inappropriate prescription and improving health outcomes and re source utilization . DESIGN Prospect i ve , r and omized , multicenter study . SETTING A private organization of nursing homes in Spain . PARTICIPANTS Sixty nursing home physicians caring for approximately 3900 nursing home residents in 37 centers were r and omized to receive an educational intervention ( 30 ) or as a control group ( 30 Output:	Deprescribing interventions were effective in reducing number of drugs and inappropriate prescribing , but a large heterogeneity in effects was observed . In general , deprescribing interventions effectively reduce medication use and inappropriate prescribing in older people . Successful deprescribing is facilitated by the combination of BCTs involving a range of intervention components
MS21853	*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 effectiveness of three applications of silver diammine fluoride ( SDF ) solution at yearly interval and three applications of SDF solution or sodium fluoride ( NaF ) varnish at weekly interval at baseline in arresting active caries in the primary teeth of preschool children . METHODS Children aged 3 - 4 years ( n = 371 ) who had at least one active caries lesion ( ICDAS codes 3 - 6 ) in their primary teeth were r and omly allocated into three groups : Group 1 - annual application of 30 % SDF solution ; Group 2 - three applications of 30 % SDF at weekly intervals ; and Group 3 - three applications of 5 % NaF varnish at weekly intervals . Follow-up examinations were performed every 6 mo nths by the same masked examiner . RESULTS After 30 months , 309 ( 83 % ) children with 1877 caries lesions remained in the study . For cavitated lesions ( ICDAS code 5 or 6 ) , the caries arrest rate of Group 1 ( 48 % ) was significantly higher than those of Group 2 ( 33 % ) and Group 3 ( 34 % ) , ( p < 0.001 ) . Results of multi-level survival analysis showed that the arrest times of cavitated lesions in both SDF groups ( Groups 1 and 2 ) were significantly shorter than that of the NaF varnish group . For moderate caries lesions without visible dentine ( ICDAS code 3 or 4 ) , the caries arrest rates were 45 % , 44 % and 51 % in Groups 1 , 2 and 3 , respectively ( p > 0.05 ) . Presence of plaque on caries lesion , tooth type and tooth surface type had an influence on caries arrest . CONCLUSION Over a 30-month period , annual applications of SDF solution is more effective than three weekly applications of NaF varnish or SDF solution at baseline in arresting active cavitated dentine caries lesions in primary teeth . CLINICAL SIGNIFICANCE As annual application of SDF solution was found to be more effective than 3 weekly applications of NaF varnish or SDF solution at baseline in arresting active cavitated dentine caries lesions , the former application protocol is preferred for young children who are available for regular caries arrest treatment The recording of multiple interval-censored failure times is common in dental research . Modeling multilevel data has been a difficult task . This paper aims to use the Bayesian approach to analyze a set of multilevel clustered interval-censored data from a clinical study to investigate the effectiveness of silver diamine fluoride and sodium fluoride varnish in arresting active dentin caries in Chinese pre-school children . The time to arrest dentin caries on a surface was measured . A three-level r and om-effects Weibull regression model was used . Analysis was performed with WinBUGS . Results revealed a strong positive correlation ( 0.596 ) among the caries lesions ’ arrest times on different surfaces from the same child . The software WinBUGS made the above complicated estimation simple . In conclusion , the annual application of silver diamine fluoride on caries lesions , and caries removal before the application , were found to shorten the arrest time Correlated or multilevel grouped survival data are common in medical and dental research . Two common approaches to analyze such data are the marginal and the r and om-effects approaches . Models and methods in the literature generally assume that the treatment effect is constant over time . A research er may be interested in study ing whether the treatment effects in a clinical trial vary over time , say fade out gradually . This is of particular clinical value when study ing the long-term effect of a treatment . This paper proposed to extend the r and om effects grouped proportional hazards models by incorporating the possibly time-varying covariate effects into the model in terms of a state-space formulation . The proposed model is very flexible and the estimation can be performed using the MCMC approach with non-informative priors in the Bayesian framework . The method is applied to a data set from a prospect i ve clinical trial investigating the effectiveness of silver diamine fluoride ( SDF ) and sodium fluoride ( NaF ) varnish in arresting active dentin caries in the Chinese preschool children . It is shown that the treatment groups with caries removal prior to the topical fluoride applications are most effective in shortening the arrest times in the first 6-month interval , but their effects fade out rapidly since then . The effects of treatment groups without caries removal prior to topical fluoride application drop at a very slow rate and can be considered as more or less constant over time . The applications of SDF solution is found to be more effective than the applications of NaF vanish Untreated dental caries in Chinese pre-school children is common . This prospect i ve controlled clinical trial investigated the effectiveness of topical fluoride applications in arresting dentin caries . Three hundred seventy-five children , aged 3 - 5 years , with carious upper anterior teeth were divided into five groups . Children in the first and second groups received annual applications of silver diamine fluoride solution ( 44,800 ppm F ) . Sodium fluoride varnish ( 22,600 ppm F ) was applied every three months to the lesions of children in the third and fourth groups . For children in the first and third groups , soft carious tissues were removed prior to fluoride application . The fifth group was the control . Three hundred eight children were followed for 30 months . The respective mean numbers of arrested carious tooth surfaces in the five groups were 2.5 , 2.8 , 1.5 , 1.5 , and 1.3 ( p < 0.001 ) . Silver diamine fluoride was found to be effective in arresting dentin caries in primary anterior teeth in pre-school children OBJECTIVES This study aim ed to compare the effectiveness of three topical fluoride application protocol s in arresting dentine caries in primary teeth of preschool children in a fluori date d area . METHODS Children aged 3 - 4 years who had at least one active dentine caries lesion were r and omly allocated into three intervention groups : Group 1-application of 30 % silver diammine fluoride ( SDF ) solution every 12 months ; Group 2-three applications of 30 % SDF solution at weekly interval at baseline ; and Group 3-three applications of 5 % sodium fluoride ( NaF ) varnish at weekly interval at baseline . A masked examiner carried out follow-up examinations every 6 months to assess whether the treated lesions had become arrested . RESULTS A total of 304 children with 1670 tooth surfaces with dentine caries received treatment at baseline . After 18 months , 275 children ( 91 % ) remained in the study . The caries arrest rates at tooth surface level were 40 % , 35 % and 27 % for Groups 1 , 2 and 3 , respectively ( p<0.001 ) . Result of the multi-level survival analysis showed that the two SDF application protocol s could shorten the time to arrest of dentine caries compared with the NaF application protocol . Presence of plaque on lesion surface , tooth type and tooth surface all had significant effects on caries arrest rates . CONCLUSIONS Annual or three consecutive weekly applications of SDF solution is more effective in arresting dentine caries in primary teeth than three consecutive weekly applications of NaF varnish . CLINICAL SIGNIFICANCE In a water fluori date d area , application of SDF solution , either three weekly applications at baseline or annually , can arrest active dentine caries lesions in primary teeth faster than three weekly applications of NaF varnish at baseline Dental caries in Chinese pre-school children is common , and restorative treatment is not readily available . This prospect i ve controlled clinical trial investigated the effectiveness of topical fluoride applications in arresting dentin caries . We divided 375 children ( aged 3 - 5 yrs ) with carious upper anterior teeth into five groups . Children in the first and second groups received annual applications of silver diamine fluoride solution ( 44,800 ppm F ) . NaF varnish ( 22,600 ppm F ) was applied every three months onto the lesions of children in the third and fourth groups . For children in the first and third groups , soft carious tissues were removed prior to fluoride application . The fifth group was the control . We followed 341 children for 18 months . The mean numbers of new caries surfaces in the five groups were 0.4 , 0.4 , 0.8 , 0.6 , and 1.2 , respectively ( p = 0.001 ) . The respective mean numbers of arrested carious tooth surfaces were 2.8 , 3.0 , 1.7 , 1.5 , and 1.0 ( p < 0.001 ) Output:	When comparing the caries arrest lesions of SDF and NaF , SDF was found to be statistically more effective in dentine caries arrest of primary teeth during the 18 and 30 month clinical examinations .
MS21854	*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 . Women attending a twin pregnancy antenatal clinic underwent cervical palpation to calculate a cervical score by subtracting dilatation from length . Those with a score of −2 or less at or before 34 weeks are at especially high risk of preterm labour . A total of 139 such women were r and omly allocated either to receive bed‐rest in hospital or to continue conventional outpatient management . No beneficial effect of bed‐rest could be identified in prolonging twin pregnancy or improving fetal outcome Nineteen women attending a special multiple pregnancy antenatal clinic with a triplet pregnancy were r and omly allocated to either bed rest in hospital from 24 weeks gestation onwards until delivery , or to continue conventional outpatient management . Conclusions are limited by the trial size , but the study suggests that routine hospitalization for bed rest decreases the incidence of preterm delivery and light-for-gestational age infants and reduces the need for intensive neonatal care . Although still compatible with change variation , the observations , if confirmed in a larger r and omized study , would have considerable implication s for clinical practice . The policy needs further evaluation in a large multicentered collaborative study The study evaluates the benefit of elective hospitalization in preventing premature deliveries of twin gestations . Three groups of women with twin gestations , having no other complications of pregnancy which could cause premature delivery , were evaluated . The study group was comprised of 43 women who were electively hospitalized between 30 - 32 and 36 weeks of gestation . Control group 1 was comprised of 55 women who were not hospitalized but were instructed to rest at home . Control group 2 was comprised of 53 women who were not hospitalized and were not instructed to rest at home . Our results showed that elective hospitalization did not significantly affect the gestational duration or the prematurity rate . However the mean birthweight difference between the study group and the two control groups were 143 + /- 83 g and 205 + /- 84 g , respectively . This result was more significant in multiparous women . The slight increase in birthweight of the hospitalized women compared to the controls , does not seem to justify the cost of hospitalization OBJECTIVE The purpose of the study was to determine whether the use of prophylactic oral ritodrine or hospitalization for bed rest can prolong pregnancy in multiple pregnancy . METHODS The study was conducted over a period of 8 years and included 189 cases of multiple pregnancy , all of which were delivered at the King Fahd Hospital of the University , Al-Khobar , Saudi Arabia , between July 1986 and August 1994 . The patients were divided into three groups : the first group included 64 patients who received oral ritodrine from the 25th to the end of the 37th week of gestation ; the second group included 57 patients who were hospitalized from the 28th to the 32nd week of gestation ; and the third group , considered the control group , included 68 patients who were managed on an outpatient basis only . Forty-six cases of multiple pregnancy were excluded from the study for a variety of reasons . RESULTS The study showed an increase in gestational age at delivery , an increase in mean birth weight and a reduction in preterm delivery in the group treated with prophylactic ritodrine ( P = 0.03 ) . In the hospitalized group there was no effect on duration of gestation or reduction in preterm delivery , but there was an increase in mean birth weight ( P = 0.04 ) . Several patients experienced troublesome side effects with ritodrine . CONCLUSION Our study indicates that the prophylactic use of beta-sympathomimetics is more effective , beneficial and less expensive than hospitalization for bed rest in prevention of preterm labor and delivery in multiple pregnancy Summary . After admission to hospital for bed rest , 200 women with multiple pregnancies were r and omly allocated to receive either 4 mg of salbutamol orally five times daily , or to receive no drug . After an average of 6 weeks treatment , no difference between the experimental groups could be detected with respect to duration of gestation , birth‐weight or any other of the outcomes of pregnancy observed Objective –To test whether a policy of hospitalization for bed rest , from 28–30 weeks gestation until delivery , lengthens the duration of gestation , improves fetal growth and decreases neonatal morbidity in twin pregnancy Of 141 women with twin pregnancies , 72 were r and omly assigned to outpatient care and 69 to hospital admission between 26 and 30 weeks ' gestation . There were no differences between the groups in the frequencies of major maternal complications in pregnancy and labour but more of those admitted to hospital than of the outpatient group had to be admitted after 30 weeks . There were no differences between the groups in the mean birthweights of the twins by birth order , or in their mean gestation at birth whether analysed by intention to treat or by the treatment given . 22 infants were delivered before 32 weeks ' gestation in the inpatient group compared with 10 in the outpatient group . With the exception of small-for- date s infants , any trend towards greater morbidity or mortality was seen in the inpatient group . The policy of routine hospital admission of women with twin pregnancies from 26 weeks ' gestation is not beneficial to mother or babies and should be ab and oned 212 women with twin pregnancies were r and omly allocated either to receive advice to rest in hospital from 32 weeks ' gestation until delivery , or to be part of a control group in which hospital admission was offered selectively ( and , on average , 5 weeks later ) . Preterm delivery was more common among women admitted routinely for bed rest than among controls , and this difference was unlikely to have occurred by chance . There is at present no scientifically acceptable evidence that this common , disruptive , and expensive obstetric policy does more good than harm A prospect i ve study was carried out to evaluate the significance and efficacy of routine hospital bed rest in prevention of premature birth and pregnancy complications compared to specialized antenatal care at the outpatient clinic of 73 twin pregnancies . The twin pregnancies were screened in health centers by means of symphysis-fundus measurement , and the diagnosis was confirmed by ultrasound examination at the outpatient clinic . On the average the ultrasonic diagnosis was performed during the 23rd gestational week ; at this visit the women were divided into two groups with similar follow-up to the end of the 29th gestational week . At this stage one of the groups was hospitalized unless there had been indications for earlier admission . In the hospital group , the mean for gestational week at delivery was 36.7 ( + /- 2.4 ) and in the outpatient group 37.4 ( + /- 1.8 ) respectively ( N.S. ) . There was no difference in the rate of pregnancy complications between the groups too . No statistical differences in the perinatal mortality ( 7.1 % and 1.1 % respectively ) or birthweights of the newborns were found , either . Present results do not support the idea of using routine hospital bed rest . It could not be proved to have positive effects on the gestational age , birth weight and perinatal mortality of the newborns , nor to the pregnancy complications . In our opinion early diagnosis of twin pregnancy is of decisive importance and specialized ambulatory follow-up could be employed instead of routine bed rest in antenatal care of twin pregnancy Output:	Women on partial bed rest in hospital were less likely to develop gestational hypertension compared with women without activity restriction at home ( RR 0.30 , 95 % CI 0.16 to 0.59 , P = 0.0004 , 141 women).Strict or partial bed rest in hospital was found to have no impact on other secondary outcomes .
MS21855	*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 study was conducted to assess the prevalence , severity and diagnostic utility of pain in patients with venous leg ulcers . A semi-structured question naire was completed by 140 consecutive patients in two specialist centres caring for patients with leg ulcers . A high proportion ( 64 % ) of the 94 patients with ulcers of purely venous aetiology reported severe pain ; 50 % of these patients were taking either mild analgesia or none at all . In 10 of 72 cases , leg elevation made the pain worse . Venous ulcers are painful . Pain in three distinct locations was reported by patients -within ulcers , around ulcers and elsewhere in the leg . The presence of severe pain does not necessarily indicate arterial disease or infection . Pain is , in general , inadequately controlled in these patients Quality of life may be considerably reduced in patients who are suffering from chronic lower limb venous insufficiency , although existing generic quality of life instruments ( NHP , SF-36 or SIP ) can not completely identify their specific complaints . The Chronic Venous Insufficiency Question naire ( CIVIQ ) has been developed by iterative process . First , a pilot group of 20 patients was used to identify a number of important features of quality of life affected by venous insufficiency , other than physical symptoms of discomfort . A second study involving 2,001 subjects was used to reduce the number of items . Subjects were asked to score both the severity of their problems and the importance they attributed to each problem on a 5-point Likert scale . The importance items found in patients with venous insufficiency were subjected to factorial analyses ( PCA , PAF ) . The final version is a 20-item self-administered question naire which explores four dimensions : psychological , physical and social functioning and pain . Internal consistency of the question naire was vali date d for each dimension ( Cronbach 's alpha > 0.820 for three out of four factors ) . Reproducibility was confirmed in a 60 patient test-retest study . Pearson 's correlation coefficients for both the four dimension subscales and for the global score at 2-week intervals were greater than 0.940 . Finally , the question naire was tested in a r and omized clinical trial of 934 patients in order to assess responsiveness and the convergent validity of the instrument , together with the patient 's own quality of life . This study demonstrated that convergence was valid : Pearson 's correlation coefficients between clinical score differences and quality of life score differences were small ( from 0.199–0.564 ) but were statistically different from 0 ( p<0.001 ) . St and ardized response mean ( SRM ) and effect size ( ES ) were calculated to assess sensitivity to change . SRM and ES both demonstrated considerble responsiveness to change ( > 0.80 ) . Reliability , face , content , construct validity and responsiveness were also determined for this specific quality of life question naire relating to venous insufficiency . Results suggest that this question naire may be used with confidence to assess quality of life in clinical trials on chronic venous insufficiency This study compared the rate of leg ulcer recurrence using two types of compression stockings and examined the factors underlying Introduction : The effect on quality of life by healing leg ulcers is not known and no vali date d disease-specific tool is available for measuring health-related quality of life ( HRQoL ) for people with venous leg ulcers . The objective of this paper was to compare four generic instruments [ MOS 36-Item Short-Form Health Survey ( SF-36 ) ; EuroQol ( EQ ) ; McGill Short Form Pain Question naire ( SF-MPQ ) and the Frenchay Activities Index ( FAI ) ] used for measuring HRQoL in people with venous leg ulcers , and to offer guidance on the most appropriate tool for research ers . Methods : Two hundred and thirty-three patients with venous leg ulcers were recruited as part of a r and omised controlled trial of the cost-effectiveness of community leg ulcer clinics . Subjects completed question naires containing the four instruments on three occasions ( initial assessment , 3 and 12 months ) . The discriminative and evaluative properties of the four instruments were compared . Results : All four instruments were acceptable to patients , taking a mean of 19.3 ( SD 6.3 ) min to complete . At initial assessment , the SF-MPQ had poorer discriminative properties than the other three instruments and was not able to distinguish between the different patient groups in relation to age and ulcer duration . The FAI was good at discriminating between the different patient groups ( at initial assessment ) in relation to age , mobility and ulcer size . At the three-month follow-up , the SF-MPQ was more responsive than the other measures and detected changes in HRQoL , whereas the EQ and SF-36 did not . At 12 months , the SF-MPQ still identified differences and the SF-36 and EQ also did at this stage . Conclusion : In the absence of a vali date d condition-specific tool for measuring changes in general health status for patients with venous leg ulcers , we make the following recommendations . For evaluating the outcome of interventions with a short-term follow-up ( three months ) in a clinical study we recommend the SF-MPQ and for 12-month follow-up in a clinical study the SF-36 , with or without the SF-MPQ STUDY OBJECTIVE To observe changes in perceived health in patients during a clinical trial of treatments for venous leg ulceration . DESIGN R and omised prospect i ve factorial trial in patients with venous ulceration . Each patient r and omised to a b and age , dressing and a drug . Perceived health assessed at entry and after 24 weeks . SETTING Outpatient departments and patient 's home . PATIENTS Two hundred patients presenting to two vascular services in Falkirk and Edinburgh with chronic ( duration > 2 months ) non-healing venous ulceration . STATISTICAL ANALYSIS AND MAIN RESULTS : Analysis using the Nottingham Health Profile revealed that after 24 weeks there were significant improvements in all subscores ( p < 0.01 ) with the exception of social isolation ( p = 0.081 ) . Patients with healed ulceration had improved in energy , pain , emotion , sleep and mobility compared with those whose ulceration failed to heal ( p < 0.05 ) . Patients r and omised to four layer b and aging had significantly better energy ( diff = 7.9 , 95 % CI 0.2 , 15.6 , p = 0.04 ) and mobility ( diff = 4.5 , 95 % CI 0.0 , 9.0 , p = 0.046 ) . This difference could be explained largely by the improved healing of patients r and omised to this b and age system ( 67/97 vs. 50/103 , OR = 2.37 , 95 % CI 1.31 , 4.27 ) . CONCLUSIONS Improvements in perceived health were significantly greater in patients whose ulcers had completely healed . Methods of treatment which offer improved healing for patients with venous leg ulceration are likely to improve patients ' perceived health status OBJECTIVES To quantify the effect of leg ulceration on health-related quality of life and to estimate a health state value for leg ulceration . DESIGN Population based case-control study . SETTING Two New Zeal and health districts ( population 540,468 people ) . SUBJECTS 241 people with a leg ulcer of any aetiology , and 224 controls r and omly selected from the electoral roll using stratified sampling . MAIN OUTCOME MEASURES health-related quality of life as measured by the eight domains of the Short Form 36 question Health Survey , adjusted for age , sex and confounding co-morbidities ; the physical component summary and mental component summary scores of the Short Form 36 question Health Survey st and ardised for age and sex ; preference-based health state value derived from the Short Form 36 question Health Survey . RESULTS Completed Short Form 36 question Health Survey question naires were available for 230 cases ( 95 % ) and 218 controls ( 97 % ) . Cases reported significantly lower mean scores than controls across all eight domains of the Short Form 36 question Health Survey ( P < 0.0005 ) . Mean domain scores for cases were also significantly lower than population norms . The mean physical component summary score for cases and controls was 45.2 versus 50.1 ( P < 0.0001 ) and the mean mental component summary score was 48.1 for cases versus 51 for controls ( P < 0.0001 ) . The mean health state values ( adjusted for age and sex ) were 0.80 for cases and 0.89 for controls . CONCLUSION Leg ulcers reduce quality of life to a similar extent as other common chronic conditions , such as arthritis and diabetes Wound pain is a serious problem for elderly patients suffering from chronic leg ulcers , and it may lead to reduced wound healing rates and reduced quality of life . Biatain-Ibu Non-adhesive ( Coloplast A/S ) , a new pain-reducing moist wound healing dressing containing ibuprofen was tested for pain reduction , safety , and efficacy on 10 + 2 patients in a single-blinded crossover study against Biatain Non-adhesive ( Coloplast A/S ) . Pain was measured with a Numeric Box Scale before , during , and after dressing change . Quality of life was measured using the World Health Organization-5 Well-Being Index . Dressing moist wound healing properties such as absorption capacity and leakage were tested together with assessment of wound exu date and blood plasma content of ibuprofen . Use of the Biatain-Ibu foam dressing correlated with a decrease in pain intensity scores from 7 in the run-in period to approximately 2.5 in the Biatain-Ibu treatment phase . Quality of life measures were improved which together with the reduced pain could contribute to faster wound healing . The moist wound healing properties of Biatain-Ibu were similar to that of the Biatain Non-adhesive and ulcer size was reduced by 24 % during the treatment period . Neither side effects nor systemic plasma concentrations of ibuprofen were observed . These data indicate that Biatain-Ibu could reduce persistent and temporary wound pain , increase Quality of life , was found safe to use , and had excellent moist wound healing properties OBJECTIVE This descriptive phenomenological study explored patients ' experiences of living with a leg ulcer . METHOD Eight participants ( five female and three male ) were recruited from a secondary care leg ulcer clinic in a large UK teaching hospital . All had current venous leg ulceration , lasting between five months and 34 years . Data collection was via in-depth semi-structured interviews . Data categories were : symptoms ; treatment ; perceptions , emotions and coping strategies ; and restrictions . RESULTS Leg ulcers have a significant impact on individuals ' lives . The degree to which this occurs varies between each person . CONCLUSION Patients need consistent treatment that incorporates benchmarking . A support network to address the needs of those living with a leg ulcer should be considered . This study 's findings should be promoted to raise awareness among health-care professionals , enabling them to provide more responsive care OBJECTIVE Health-related quality of life ( HRQOL ) affects outcome in chronic diseases such as inflammatory bowel disease ( IBD ) . The inflammatory bowel disease question naire ( IBDQ ) , a disease-specific HRQOL question naire , can define changes in health status in IBD , but simple instruments are needed for daily application . The present study proposed to develop a short version of the IBDQ , the SIBDQ , for community physicians . METHODS Using data from a clinical trial in 149 patients with Crohn 's disease , 10 items were selected ( by forward stepwise regression ) that best explained the variance of the IBDQ or dimensional scores ( bowel , systemic , social , emotional ) . The validity , reliability , and responsiveness of the SIBDQ were then assessed in 150 different patients with Crohn 's disease and 45 with ulcerative colitis . All scores were reported with a 7-point scale ( 1 = poor HRQOL , 7 = optimum HRQOL ) . RESULTS Mean SIBDQ scores were similar ( p = 0.22 ) in Crohn 's patients among 14 participating centers at study entry . Mean scores were lower in active Crohn 's disease ( range 4.00 - 4.92 ) than inactive disease ( range 4.67 - 5.83 ; p = 0.0015 ) . In active ulcerative colitis , the mean SIBDQ was 4.79 + /- 1.17 compared to 5.90 + /- 0.80 ( p = 0.0006 ) in inactive disease . The SIBDQ explained 92 % and 90 % of the IBDQ variance in Crohn 's disease and ulcerative colitis , respectively . In patients with stable Crohn 's disease , the test-retest reliability coefficient was 0.65 and Crohnbach 's alpha was 0.78 , indicating good reliability . In patients with Crohn 's disease who relapsed during follow-up , the mean SIBDQ decreased by -0.93 + 0.55 ( p = 0.001 ) . CONCLUSION The SIBDQ is valid , reliable , and able to detect meaningful clinical changes in HRQOL that might occur in the office setting AIM To explore the characteristics of venous and arterial leg ulcer pain among people cared for in the community . BACKGROUND There is little information available concerning the different characteristics of pain result ing from venous and arterial leg ulcers . The identification of clear differences in pain experience might aid recognition of arterial deterioration and provide a useful adjunct for existing diagnostic procedures . DESIGN This was a prospect i ve interview-based survey . METHOD Structured interviews were conducted with each of the participants in their home . Ulcer history , pain ( McGill pain question naire and verbal rating scale ) and factors influencing pain were assessed . RESULTS Fifty-two women and 27 men aged 77.7 Output:	The disease-specific instruments showed limitations in relation to their applicability to venous ulcer patients because of flaws in design or validation . The literature on quality of life related to venous ulceration failed to sufficiently distinguish between those with different causes of leg ulceration . There appeared to be problems with the ability of current quality of life instruments to detect changes in quality of life related to ulcer healing . There appears to be an opportunity for nurses to develop a health-related quality of life health-related quality of life instruments to evaluate their impact on patient outcomes . Such instruments could potentially allow nursing interventions to be assessed more effectively than the recently proposed nursing metrics
MS21856	*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 assess whether adding clopidogrel to acetylsalicylic acid ( ASA ) has a long-term protective vascular effect in patients with lacunar stroke while taking ASA . Methods : Post hoc analysis of 838 patients with ASA failure and recent lacunar stroke from the Secondary Prevention of Small Subcortical Strokes Trial ( SPS3 ) cohort r and omly allocated to aspirin ( 325 mg/day ) and clopidogrel ( 75 mg/day ) or placebo . Primary efficacy outcome was stroke recurrence ( ischemic and intracranial hemorrhage ) and main safety outcome was major extracranial hemorrhage . Patients were followed for a mean period of 3.5 years . Results : The ASA failure group had a significantly higher risk of vascular events including ischemic stroke when compared with the non – ASA failure group ( n = 2,151 ) in SPS3 ( p = 0.03 ) . Mean age was 65.6 years and 65 % were men . The risk of recurrent stroke was not reduced in the dual antiplatelet group , 3.1 % per year , compared to the aspirin-only group , 3.3 % per year ( hazard ratio [ HR ] 0.91 ; 95 % confidence interval [ CI ] 0.61–1.37 ) . There was also no difference between groups for ischemic stroke ( HR 0.90 ; 95 % CI 0.59–1.38 ) . The risk of gastrointestinal bleeding was higher in the dual antiplatelet group ( HR 2.7 ; 95 % CI 1.1–6.9 ) ; however , the risk of intracranial hemorrhage was not different . Conclusions : In patients with a recent lacunar stroke while taking ASA , the addition of clopidogrel did not result in reduction of vascular events vs continuing ASA only . Classification of evidence : This study provides Class I evidence that for patients with recent lacunar stroke while taking ASA , adding clopidogrel as compared to continuing ASA alone does not reduce the risk of recurrent stroke BACKGROUND Patients with transient ischaemic attack ( TIA ) or minor stroke are at high immediate risk of stroke . The optimum early treatment options for these patients are not known . METHODS Within 24 h of symptom onset , we r and omly assigned , in a factorial design , 392 patients with TIA or minor stroke to clopidogrel ( 300 mg loading dose then 75 mg daily ; 198 patients ) or placebo ( 194 patients ) , and simvastatin ( 40 mg daily ; 199 patients ) or placebo ( 193 patients ) . All patients were also given aspirin and were followed for 90 days . Descriptive analyses were done by intention to treat . The primary outcome was total stroke ( ischaemic and haemorrhagic ) within 90 days . Safety outcomes included haemorrhage related to clopidogrel and myositis related to simvastatin . This study is registered as an International St and ard R and omised Controlled Trial ( number 35624812 ) and with Clinical Trials.gov ( NCT00109382 ) . FINDINGS The median time to stroke outcome was 1 day ( range 0 - 62 days ) . The trial was stopped early due to a failure to recruit patients at the prespecified minimum enrolment rate because of increased use of statins . 14 ( 7.1 % ) patients on clopidogrel had a stroke within 90 days compared with 21 ( 10.8 % ) patients on placebo ( risk ratio 0.7 [ 95 % CI 0.3 - 1.2 ] ; absolute risk reduction -3.8 % [ 95 % CI -9.4 to 1.9 ] ; p=0.19 ) . 21 ( 10.6 % ) patients on simvastatin had a stroke within 90 days compared with 14 ( 7.3 % ) patients on placebo ( risk ratio 1.3 [ 0.7 - 2.4 ] ; absolute risk increase 3.3 % [ -2.3 to 8.9 ] ; p=0.25 ) . The interaction between clopidogrel and simvastatin was not significant ( p=0.64 ) . Two patients on clopidogrel had intracranial haemorrhage compared with none on placebo ( absolute risk increase 1.0 % [ -0.4 to 2.4 ] ; p=0.5 ) . There was no difference between groups for the simvastatin safety outcomes . INTERPRETATION Immediately after TIA or minor stroke , patients are at high risk of stroke , which might be reduced by using clopidogrel in addition to aspirin . The haemorrhagic risks of the combination of aspirin and clopidogrel do not seem to offset this potential benefit . We were unable to provide evidence of benefit of simvastatin in this setting . This aggressive prevention approach merits further study BACKGROUND Few r and omised clinical trials have investigated the use of antithrombotic drugs for early secondary prevention of stroke or transient ischaemic attack in patients with intracranial atherosclerotic stenosis . Microembolic signals , detected by transcranial doppler , are a surrogate marker of future stroke risk and have been used to show treatment efficacy in patients with extracranial carotid stenosis . We aim ed to investigate whether treatment with clopidogrel plus aspirin reduced the number of microembolic signals detected with transcranial doppler ultrasound compared with aspirin alone in patients with recent stroke . METHODS The clopidogrel plus aspirin for infa rct ion reduction in acute stroke or transient ischaemic attack patients with large artery stenosis and microembolic signals ( CLAIR ) trial was a r and omised , open-label , blinded-endpoint trial . Between Oct 28 , 2003 , and Nov 19 , 2008 , patients with acute ischaemic stroke or transient ischaemic attack who had symptomatic large artery stenosis in the cerebral or carotid arteries and in whom microembolic signals were present on transcranial doppler were r and omly assigned within 7 days of symptom onset to receive clopidogrel ( 300 mg for the first day , then 75 mg daily ) plus aspirin ( 75 - 160 mg daily ) or aspirin alone ( 75 - 160 mg daily ) for 7 days . Patients were r and omly assigned in blocks of four or six by use of a r and omisation website . Monitoring of microembolic signals on transcranial doppler was done on days 2 and 7 . The primary endpoint was the proportion of patients who had microembolic signals on day 2 . Analysis was by modified intention to treat . All analyses were done by an investigator masked to both patient identity and the day the recording was taken . This trial is registered with the Centre for Clinical Trials , Chinese University of Hong Kong , number CUHK_CCT00164 . FINDINGS 100 patients were r and omly assigned to clopidogrel plus aspirin ( n=47 ) or aspirin monotherapy ( n=53 ) . 93 of 100 patients had symptomatic intracranial stenosis in either the intracranial internal carotid artery or the middle cerebral artery : 45 of 46 in the dual therapy group and 48 of 52 in the monotherapy group . At day 2 , 14 of 45 patients in the dual therapy group and 27 of 50 patients in the monotherapy group for whom data were available had at least one microembolic signal on transcranial doppler ( relative risk reduction 42.4 % , 95 % CI 4.6 - 65.2 ; p=0.025 ) . Adverse events were similar in the two groups . No patients had intracranial or severe systemic haemorrhage , but two patients in the dual therapy group had minor haemorrhages . INTERPRETATION Combination therapy with clopidogrel and aspirin is more effective than aspirin alone in reducing microembolic signals in patients with predominantly intracranial symptomatic stenosis . Clinical trials are now warranted to investigate whether this combination treatment also results in a reduction in stroke incidence Background — Evidence for efficacy of dual antiplatelet therapy in stroke is limited . Symptomatic carotid stenosis patients are at high risk of early recurrent stroke . In this group , asymptomatic microembolic signals ( MES ) , detected by transcranial Doppler ultrasound ( TCD ) , are markers of future stroke and transient ischemic attack ( TIA ) risk . They offer a surrogate marker to evaluate antiplatelet therapy , but no multicenter study has evaluated the feasibility of this approach . Methods and Results —Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic Carotid Stenosis ( CARESS ) is a r and omized , double-blind study in subjects with recently symptomatic ≥50 % carotid stenosis . Patients were screened with TCD , and if MES were detected , they were r and omized to clopidogrel and aspirin or aspirin monotherapy . Repeated TCD recordings were made on days 2 and 7 . MES were detected in 110 of 230 patients by online analysis at baseline , of whom 107 were r and omized . Intention-to-treat analysis revealed a significant reduction in the primary end point : 43.8 % of dual-therapy patients were MES positive on day 7 , as compared with 72.7 % of monotherapy patients ( relative risk reduction 39.8 % ; 95 % CI , 13.8 to 58.0 ; P=0.0046 ) . The secondary end point of MES frequency per hour was reduced ( compared with baseline ) by 61.4 % ( 95 % CI , 31.6 to 78.2 ; P=0.0013 ) in the dual-therapy group at day 7 and by 61.6 % ( 95 % CI , 34.9 to 77.4 ; P=0.0005 ) on day 2 . There were 4 recurrent strokes and 7 TIAs in the monotherapy group versus no stroke and 4 TIAs in the dual-therapy group that were treatment emergent and ipsilateral to the qualifying carotid stenosis ; 2 additional ipsilateral TIAs occurred before treatment started . MES frequency was greater in the 17 patients with recurrent ipsilateral events compared with the 90 without ( mean±SD : 24.4±27.7 versus 8.9±11.5 per hour ; P=0.0003 ) . Conclusions —In patients with recently symptomatic carotid stenosis , combination therapy with clopidogrel and aspirin is more effective than aspirin alone in reducing asymptomatic embolization . Doppler MES detection is a feasible method to evaluate the efficacy of antiplatelet therapy in multicenter studies Background : Little information is available about public knowledge of TIA and prevalence of a TIA diagnosis . Methods : The National Stroke Association sponsored a telephone survey by single-stage r and om-digit dialing of noninstitutionalized US residents ≥18 years old , which was conducted in 1999 . Demographic characteristics of participants were compared to the US population to produce weights for projections . Independent predictors of knowledge and diagnosis of TIA were determined by including all demographic characteristics in logistic regression models . Results : Among 10,112 participants , 2.3 % reported having been told by a physician that they had a TIA . Older age , lower income , and fewer years of education were independently associated with a diagnosis of TIA . Of those with TIA , only 64 % saw a physician within 24 hours of the event . A physician diagnosis of stroke was reported by 2.3 % of participants , of whom 19 % recalled having had a TIA before the stroke . An additional 3.2 % of participants recalled symptoms consistent with TIA but did not seek medical attention . Only 8.2 % correctly related the definition of TIA and 8.6 % could identify a typical symptom . Men , nonwhites , and those with lower income and fewer years of education were less likely to be knowledgeable about TIA . Conclusions : An estimated 4.9 million people in the US report a diagnosis of TIA , and many more recall symptoms consistent with TIA but do not seek medical attention . Reducing stroke risk after TIA could have substantial impact on public health but will require public education about the importance of having stroke symptoms evaluated , even if they resolve BACKGROUND Evidence is available on the effectiveness and costs of treatments to reduce stroke risk in long-term secondary prevention . However , there are few data on the costs and outcomes of urgent assessment and treatment after the onset of transient ischaemic attack ( TIA ) or minor stroke . The Early use of eXisting PREventive Strategies for Stroke ( EXPRESS ) study showed that urgent assessment and treatment reduced the 90-day risk of recurrent stroke by about 80 % . We now report the effect of the EXPRESS intervention on admissions to hospital , costs , and disability . METHODS EXPRESS was a prospect i ve population -based before ( phase 1 : April 1 , 2002 , to Sept 30 , 2004 ) versus after ( phase 2 : Oct 1 , 2004 , to March 31 , 2007 ) study of the effect of early assessment and treatment of TIA or minor stroke on the risk of early recurrent stroke . This report assesses the effect of the introduction of the phase 2 clinic on admissions to hospital within 90 days , hospital bed-days , hospital costs , and 6-month new disability ( progression from no disability before event [ modified Rankin scale score < or = 2 points ] to disability at 6 months [ modified Rankin scale score > 2 points ] Output:	Therefore , the treatment with Clop + ASA seems safe as well as effective for decreasing stroke recurrence . In addition , this is related to a statistically insignificant trend in increasing vascular mortalities , MI , and primary hemorrhagic events .
MS21857	*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 VEGF and VEGF receptor-2-mediated angiogenesis contribute to hepatocellular carcinoma pathogenesis . Ramucirumab is a recombinant IgG1 monoclonal antibody and VEGF receptor-2 antagonist . We aim ed to assess the safety and efficacy of ramucirumab in advanced hepatocellular carcinoma following first-line therapy with sorafenib . METHODS In this r and omised , placebo-controlled , double-blind , multicentre , phase 3 trial ( REACH ) , patients were enrolled from 154 centres in 27 countries . Eligible patients were aged 18 years or older , had hepatocellular carcinoma with Barcelona Clinic Liver Cancer stage C disease or stage B disease that was refractory or not amenable to locoregional therapy , had Child-Pugh A liver disease , an Eastern Cooperative Oncology Group performance status of 0 or 1 , had previously received sorafenib ( stopped because of progression or intolerance ) , and had adequate haematological and biochemical parameters . Patients were r and omly assigned ( 1:1 ) to receive intravenous ramucirumab ( 8 mg/kg ) or placebo every 2 weeks , plus best supportive care , until disease progression , unacceptable toxicity , or death . R and omisation was stratified by geographic region and cause of liver disease with a stratified permuted block method . Patients , medical staff , investigators , and the funder were masked to treatment assignment . The primary endpoint was overall survival in the intention-to-treat population . This study is registered with Clinical Trials.gov , number NCT01140347 . FINDINGS Between Nov 4 , 2010 , and April 18 , 2013 , 565 patients were enrolled , of whom 283 were assigned to ramucirumab and 282 were assigned to placebo . Median overall survival for the ramucirumab group was 9·2 months ( 95 % CI 8·0 - 10·6 ) versus 7·6 months ( 6·0 - 9·3 ) for the placebo group ( HR 0·87 [ 95 % CI 0·72 - 1·05 ] ; p=0·14 ) . Grade 3 or greater adverse events occurring in 5 % or more of patients in either treatment group were ascites ( 13 [ 5 % ] of 277 patients treated with ramucirumab vs 11 [ 4 % ] of 276 patients treated with placebo ) , hypertension ( 34 [ 12 % ] vs ten [ 4 % ] ) , asthenia ( 14 [ 5 % ] vs five [ 2 % ] ) , malignant neoplasm progression ( 18 [ 6 % ] vs 11 [ 4 % ] ) , increased aspartate aminotransferase concentration ( 15 [ 5 % ] vs 23 [ 8 % ] ) , thrombocytopenia ( 13 [ 5 % ] vs one [ < 1 % ] ) , hyperbilirubinaemia ( three [ 1 % ] vs 13 [ 5 % ] ) , and increased blood bilirubin ( five [ 2 % ] vs 14 [ 5 % ] ) . The most frequently reported ( ≥1 % ) treatment-emergent serious adverse event of any grade or grade 3 or more was malignant neoplasm progression . INTERPRETATION Second-line treatment with ramucirumab did not significantly improve survival over placebo in patients with advanced hepatocellular carcinoma . No new safety signals were noted in eligible patients and the safety profile is manageable . FUNDING Eli Lilly and PURPOSE This phase II study of sorafenib , an oral multikinase inhibitor that targets Raf kinase and receptor tyrosine kinases , assessed efficacy , toxicity , pharmacokinetics , and biomarkers in advanced hepatocellular carcinoma ( HCC ) patients . METHODS Patients with inoperable HCC , no prior systemic treatment , and Child-Pugh ( CP ) A or B , received continuous , oral sorafenib 400 mg bid in 4-week cycles . Tumor response was assessed every two cycles using modified WHO criteria . Sorafenib pharmacokinetics were measured in plasma sample s. Biomarker analysis included phosphorylated extracellular signal regulated kinase ( pERK ) in pretreatment biopsies ( immunohistochemistry ) and blood-cell RNA expression patterns in selected patients . RESULTS Of 137 patients treated ( male , 71 % ; median age , 69 years ) , 72 % had CP A , and 28 % had CP B. On the basis of independent assessment , three ( 2.2 % ) patients achieved a partial response , eight ( 5.8 % ) had a minor response , and 46 ( 33.6 % ) had stable disease for at least 16 weeks . Investigator-assessed median time to progression ( TTP ) was 4.2 months , and median overall survival was 9.2 months . Grade 3/4 drug-related toxicities included fatigue ( 9.5 % ) , diarrhea ( 8.0 % ) , and h and -foot skin reaction ( 5.1 % ) . There were no significant pharmacokinetic differences between CP A and B patients . Pretreatment tumor pERK levels correlated with TTP . A panel of 18 expressed genes was identified that distinguished " nonprogressors " from " progressors " with an estimated 100 % accuracy . CONCLUSION Although single-agent sorafenib has modest efficacy in HCC , the manageable toxicity and mechanisms of action support a role for combination regimens with other anticancer agents PURPOSE Open-label , phase III trial evaluating whether sunitinib was superior or equivalent to sorafenib in hepatocellular cancer . PATIENTS AND METHODS Patients were stratified and r and omly assigned to receive sunitinib 37.5 mg once per day or sorafenib 400 mg twice per day . Primary end point was overall survival ( OS ) . RESULTS Early trial termination occurred for futility and safety reasons . A total of 1,074 patients were r and omly assigned to the study ( sunitinib arm , n = 530 ; sorafenib arm , n = 544 ) . For sunitinib and sorafenib , respectively , median OS was 7.9 versus 10.2 months ( hazard ratio [ HR ] , 1.30 ; one-sided P = .9990 ; two-sided P = .0014 ) ; median progression-free survival ( PFS ; 3.6 v 3.0 months ; HR , 1.13 ; one-sided P = .8785 ; two-sided P = .2286 ) and time to progression ( TTP ; 4.1 v 3.8 months ; HR , 1.13 ; one-sided P = .8312 ; two-sided P = .3082 ) were comparable . Median OS was similar among Asian ( 7.7 v 8.8 months ; HR , 1.21 ; one-sided P = .9829 ) and hepatitis B-infected patients ( 7.6 v 8.0 months ; HR , 1.10 ; one-sided P = .8286 ) , but was shorter with sunitinib in hepatitis C-infected patients ( 9.2 v 17.6 months ; HR , 1.52 ; one-sided P = .9835 ) . Sunitinib was associated with more frequent and severe adverse events ( AEs ) than sorafenib . Common grade 3/4 AEs were thrombocytopenia ( 29.7 % ) and neutropenia ( 25.7 % ) for sunitinib ; h and -foot syndrome ( 21.2 % ) for sorafenib . Discontinuations owing to AEs were similar ( sunitinib , 13.3 % ; sorafenib , 12.7 % ) . CONCLUSION OS with sunitinib was not superior or equivalent but was significantly inferior to sorafenib . OS was comparable in Asian and hepatitis B-infected patients . OS was superior in hepatitis C-infected patients who received sorafenib . Sunitinib-treated patients reported more frequent and severe toxicity BACKGROUND The efficacy and safety of axitinib , a potent and selective vascular endothelial growth factor receptors 1 - 3 inhibitor , combined with best supportive care ( BSC ) was evaluated in a global , r and omized , placebo-controlled phase II trial in patients with locally advanced or metastatic hepatocellular carcinoma ( HCC ) . PATIENTS AND METHODS Patients with HCC and Child-Pugh Class A who progressed on or were intolerant to one prior antiangiogenic therapy were stratified by tumour invasion ( presence/absence of extrahepatic spread and /or vascular invasion ) and region ( Asian/non-Asian ) and r and omized ( 2:1 ) to axitinib/BSC ( starting dose 5 mg twice-daily ) or placebo/BSC . The primary end point was overall survival ( OS ) . RESULTS The estimated hazard ratio for OS was 0.907 [ 95 % confidence interval ( CI ) 0.646 - 1.274 ; one-sided stratified P = 0.287 ] for axitinib/BSC ( n = 134 ) versus placebo/BSC ( n = 68 ) , with the median ( 95 % CI ) of 12.7 ( 10.2 - 14.9 ) versus 9.7 ( 5.9 - 11.8 ) months , respectively . Results of prespecified subgroup analyses in Asian versus non-Asian patients or presence versus absence of tumour invasion were consistent with the overall population . Improvements favouring axitinib/BSC ( P < 0.01 ) were observed in secondary efficacy end point analyses [ progression-free survival ( PFS ) , time to tumour progression ( TTP ) , and clinical benefit rate ( CBR ) ] , and were retained among Asian patients in the prespecified subgroup analyses . Overall response rate did not differ significantly between treatments and patient-reported outcomes favoured placebo/BSC . Most common all-causality adverse events with axitinib/BSC were diarrhoea ( 54 % ) , hypertension ( 54 % ) , and decreased appetite ( 47 % ) . Baseline serum analyses identified potential new prognostic ( interleukin-6 , E-selectin , interleukin-8 , angiopoietin-2 , migration inhibitory factor , and c-MET ) or predictive ( E-selectin and stromal-derived factor-1 ) factors for survival . CONCLUSIONS Axitinib/BSC did not improve OS over placebo/BSC in the overall population or in stratification subgroups . However , axitinib/BSC result ed in significantly longer PFS and TTP and higher CBR , with acceptable toxicity in patients with advanced HCC . TRIAL REGISTRATION Clinical Trials.gov , NCT01210495 BACKGROUND Ramucirumab is a human IgG1 monoclonal antibody that targets the extracellular domain of VEGFR-2 . We aim ed to assess efficacy and safety of treatment with docetaxel plus ramucirumab or placebo as second-line treatment for patients with stage IV non-small-cell-lung cancer ( NSCLC ) after platinum-based therapy . METHODS In this multicentre , double-blind , r and omised phase 3 trial ( REVEL ) , we enrolled patients with squamous or non-squamous NSCLC who had progressed during or after a first-line platinum-based chemotherapy regimen . Patients were r and omly allocated ( 1:1 ) with a central ised , interactive voice-response system ( stratified by sex , region , performance status , and previous maintenance therapy [ yes vs no ] ) to receive docetaxel 75 mg/m(2 ) and either ramucirumab ( 10 mg/kg ) or placebo on day 1 of a 21 day cycle until disease progression , unacceptable toxicity , withdrawal , or death . The primary endpoint was overall survival in all patients allocated to treatment . We assessed adverse events according to treatment received . This study is registered with Clinical Trials.gov , number NCT01168973 . FINDINGS Between Dec 3 , 2010 , and Jan 24 , 2013 , we screened 1825 patients , of whom 1253 patients were r and omly allocated to treatment . Median overall survival was 10·5 months ( IQR 5·1 - 21·2 ) for 628 patients allocated ramucirumab plus docetaxel and 9·1 months ( 4·2 - 18·0 ) for 625 patients who received placebo plus docetaxel ( hazard ratio 0·86 , 95 % CI 0·75 - 0·98 ; p=0·023 ) . Median progression-free survival was 4·5 months ( IQR 2·3 - 8·3 ) for the ramucirumab group compared with 3·0 months ( 1·4 - 6·9 ) for the control group ( 0·76 , 0·68 - 0·86 ; p<0·0001 ) . We noted treatment-emergent adverse events in 613 ( 98 % ) of 627 patients in the ramucirumab safety population and 594 ( 95 % ) of 618 patients in the control safety population . The most common grade 3 or worse adverse events were neutropenia ( 306 patients [ 49 % ] in the ram Output:	Conclusions The findings of this study show that elderly HCC patients who relapsed after a first-line sorafenib treatment obtains a survival benefits from anti-VEGF agents rechallenge .
MS21858	*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 study consisted of a cost-minimisation analysis since the findings from a multicentre r and omised phase III trial showed that pegylated liposomal doxorubicin hydrochloride was at least as efficacious as topotecan . An economic model from the Spanish hospitals perspective was constructed to compare the costs derived from the treatment using both drugs in patients with recurrent epithelial ovarian cancer who failed a first-line platinum-containing regimen . The cost evaluation included direct medical costs : drug , drug administration and costs of managing adverse events . Estimation of re sources used in managing adverse events was made retrospectively through an expert panel . Results obtained per patient were : cost of drug and administration , 8647.70 euros for pegylated liposomal doxorubicin hydrochloride and 8519.94 euros for topotecan , while cost of managing adverse events was 967.02 euros in the pegylated liposomal doxorubicin hydrochloride arm and 3304.75 euros for topotecan . The total cost per patient was therefore estimated to be 9614.72 euros for pegylated liposomal doxorubicin hydrochloride and 11 824.69 euros for topotecan , showing that pegylated liposomal doxorubicin hydrochloride produces a cost saving of 2209.97 euros per patient in comparison to topotecan . Sensitivity analyses verified the robustness of the results . These findings suggest that pegylated liposomal doxorubicin hydrochloride is an efficient therapy and can be used as a cost-saving option for treatment of patients with recurrent epithelial ovarian cancer who have failed a first-line platinum-containing regimen In the r and omised clinical trial E1684 , the administration of interferon ( IFN ) alpha-2b result ed in prolonged disease-free and overall survival in high-risk melanoma patients following surgical resection . However , and considering the cost and toxicity of IFN , the convenience of its widespread use should be evaluated . The aim of this study was to analyse the cost-effectiveness ratio of adjuvant therapy with IFN alpha-2b in melanoma patients versus an untreated control group . A Markov model was used to compare two hypothetical cohorts of 1000 patients aged 50 years , according to the clinical outcome of the E1684 study . The cohort of patients treated with IFN alpha-2b has an increased overall survival of 1.90 years during the patient 's lifetime . The incremental discounted cost per life year gained of IFN versus observation is 9015 Euros according to the projection generated by the model . The sensitivity analysis demonstrated that changes in the most relevant study end-points do not modify the study outcome . In conclusion , in high-risk melanoma patients following surgical resection , the cost-effectiveness of IFN alpha-2b ( at a dose of 20 MU/m2/day , 5 days per week for one month , followed by 10 MU/m2 TIW , up to one complete year of therapy ) versus an untreated control group is within the limits established in health economics to determine if adoption of a new treatment is economically justified and is comparable with other interventions in which cost-effectiveness is acceptable to the National Health System Introduction The r and omised controlled trial BCIRG001 has recently demonstrated that docetaxel in combination with doxorubicin and cyclophosphamide ( TAC ) has better efficacy than the st and ard treatment ( FAC , i.e. , 5-fluorouracil , doxorubicin and cyclophosphamide ) in the adjuvant treatment of patients with node-positive breast cancer . The cost-effectiveness of TAC vs. FAC in the Spanish setting is analysed . Patients and methods Clinical outcomes from trial BCIRG001 were combined with Spanish costs and long-term efficacy of FAC and TAC extrapolated up to 5 years by means of a Markov model . Results are shown as cost per life year gained ( C/LYG ) and cost per quality -adjusted life year ( C/QALY ) . Costs and effects were discounted at a rate of 3 % . Results Mean survival was 17.8 and 16.5 years for TAC and FAC , with total costs of € 14,611 and € 11,586 , respectively . The results of the cost-effectiveness analysis showed that TAC achieves a C/LYG and a C/QALY of only € 2345 and € 2631 , respectively . Sensitivity analysis confirmed the robustness of the results . Conclusions Combined therapy based on docetaxel ( TAC ) is not only an effective option , but also presents a favourable cost-effectiveness ratio , clearly below the Spanish efficiency threshold in all the scenarios considered A large r and omized clinical trial in advanced , previously untreated , non-small cell lung cancer ( NSCLC ) patients revealed better response rates and better tolerance for paclitaxel+cisplatin ( TAXCIS ) compared to teniposide+cisplatin ( TENCIS ) . Since economic evidence is receiving increasing attention in health care , we conducted an economic evaluation based on the trial results in The Netherl and s , Belgium , France and Spain . The evaluation was based on ( i ) differences in drug costs , ( ii ) differences in chemotherapy administration and ( iii ) the economic consequences of significantly different clinical outcomes in the trial : anemia , thrombocytopenia , neutropenia , neuropathy and arthralgia/myalgia . Data regarding medical re source utilization were obtained from clinician interviews using a Delphi technique and vali date d by patient charts analysis . Differences in medical management occurred across countries , but TAXCIS was cost-additive in all countries , i.e. the extra cost of chemotherapy was only partially compensated by savings in medical re source use , result ing in a net cost per patient of US$ 2311 . In the trial , TAXCIS therapy produced a 37 % response rate compared to 26 % for TENCIS . The cost per extra responder for TAXCIS is on average US$ 21011 , which is comparable to the cost per responder obtained with TENCIS ( US$ 27266 ) . Thus , the cost-effectiveness of TAXCIS , expressed in cost per responder , is similar to the cost-effectiveness obtained with TENCIS INTRODUCTION Information on the relative cost-effectiveness of treatments for cancer is being increasingly sought as pressure on health care re sources increases . The objective of this study was to assess the cost-effectiveness of gemcitabine/cisplatin ( GC ) versus cisplatin/etoposide ( CE ) in patients with advanced non-small cell lung cancer ( NSCLC ) , using re source utilization data collected in conjunction with the first r and omized clinical trial comparing both combinations . METHODS Efficacy and medical care re source utilization data were collected prospect ively in an open-label , multicenter , r and omized , comparative , phase III trial conducted in Spain which compared gemcitabine/cisplatin and cisplatin/etoposide in 135 chemonaive patients with Stage IIIB or IV NSCLC . There were no differences between both regimens when survival was used as primary end-point , so a cost-minimization analysis was used to compare them . In addition , cost-effectiveness analyses were conducted when percentage of responses and time to progression were used as secondary end-points . RESULTS There were no differences between both regimens when survival was selected as the efficacy end-point . Despite the higher chemotherapy cost of GC when compared to CE , there were no differences in total direct costs ( 584523 pts for GC and 589630 pts for CE ; P = NS ) between both regimens . Potential savings with GC were mainly associated with a decrease in hospitalization rate . There were differences in favor of GC when response rate ( 40.6 % for GC and 21.9 % for CE ; P<0.05 ) and time to disease progression ( 8.7 months for GC and 7.2 months for CE ; P<0 . 05 ) were used as clinical end-points . GC presented a favorable cost-effectiveness profile when compared to CE . CONCLUSIONS This prospect i ve economic evaluation conducted alongside a clinical trial offers valuable preliminary information on the potential efficiency of the combination gemcitabine-cisplatin in NSCLC . Future assessment s based on larger clinical trials focused on survival and naturalistic economic studies conducted in real clinical practice setting s are necessary to confirm these findings Output:	The major conclusion is that the absence of regulations concerning the application of the efficiency criterion in decision-making on the subject of price and financing and , most importantly , the fact that these are not included in Spanish hospitals forms make it difficult to analyse the real impact of economic evaluations of cancer treatments on such decisions
MS21859	*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 A prospect i ve controlled intervention cohort study in cancer pain patients ( n = 50 per group ) admitted to radiation oncology wards ( 62 beds , 3 wards ) was conducted in a 1621‐bed university hospital . We investigated the effect of an intervention consisting of daily pain assessment using the numeric visual analog scale ( NVAS ) and pain therapy counseling to clinicians based on a computerized clinical decision support system ( CDSS ) to correct deviations from pain therapy guidelines . Effects on guideline adherence ( primary outcome ) , pain relief ( NVAS ) at rest and during physical activity ( both groups : cross‐sectional assessment on day 5 ; intervention group : every day assessment ) , co‐analgesic prescription , and acceptance rates of recommendations ( secondary outcomes ) were assessed . The number of patients with at least one deviation from guidelines at discharge was decreased by the intervention from 37 ( 74 % ) in controls to 7 ( 14 % , p < 0.001 ) . In the intervention group , pain ( NVAS ) decreased during hospital stay at rest from 3.0 ( Δ0.5 ( Q75 % − Q25 % ) = 3.0 ) on admission to 1.5 ( Δ0.5 = 1.0 ) at discharge ( p < 0.01 ) and during physical activity from 7.0 ( Δ0.5 = 4.0 ) on admission to 2.5 ( Δ0.5 = 3.8 ) at discharge ( p < 0.001 ) . At discharge , the number of patients treated with co‐analgesics increased from 23 ( 46 % ) in controls to 33 ( 66 % ) in the intervention group ( p = 0.04 ) . From 279 recommendations issued in the intervention 85 % were fully accepted by the physicians . Deviations from well‐established guidelines are frequent in pain therapy . A multidisciplinary pain management increased adherence to pain management guidelines Introduction The prevalence of pain in patients with cancer is still too high . Factors relating to ineffective pain treatment fall into three categories : the health care system , professional care providers , and patients . In patients , various barriers lead to noncompliance . Previous educational interventions have increased their knowledge of pain and decreased short-term pain levels . In this r and omized controlled trial , the authors investigated how an intensive home-based education program given by nurses affected short-term and long-term pain levels . Material s and methods One hundred and twenty cancer patients were r and omized to receive either the pain education program ( PEP ) or usual care . Pain , knowledge , quality of life , anxiety , and depression were measured at baseline and after 4 and 8 weeks . In the intervention group , effects on symptom levels were communicated to the treating physician . Results The level of pain had decreased at 4 weeks , but not at 8 weeks . Significant decreases in pain only persisted in those patients with a high pain score at baseline . Knowledge of pain significantly increased in the intervention group . No correlation was found between increased pain knowledge and decreased pain levels . Conclusions The PEP given by nurses lowered pain intensity levels in cancer patients and increased their knowledge of pain . More attention should be paid to patient education and to communication between patients and health professionals regarding pain and pain management OBJECTIVE To test a pathway through which a tailored , pain management education-coaching intervention could contribute to better cancer pain control through the effects of patients ' communication about pain on physician prescribing of pain medication . METHODS Secondary analysis of data from a r and omized controlled trial that tested the effects of a tailored education-coaching intervention on pain control for patients with advanced cancer . The current analysis focused on a subset of the patients ( n = 135 ) who agreed to have their consultations audio-recorded . Patients ' active communication about pain ( e.g. , expressing questions , concerns , and preferences about pain-related issues ) was coded from audio-recordings . Change in pain medication was measured by patient self-report . Improvement in pain control was scored as the difference between baseline pain score and pain reported at 6 weeks . RESULTS Patients ' pain-related communication was a significant predictor of patient-reported changes in physician prescribing of pain medication ( p < .0001 ) and mediated the effect of baseline pain on medication change . Other predictors of change in pain medication were age ( younger ) and having participated in the intervention ( as opposed to usual care ) . Of the patients reporting adjustment in pain medications , 49 % experienced better pain control compared with only 27 % of patients reporting no change in pain management ( p < .02 ) . CONCLUSIONS Cancer patients who ask questions , express concerns , and state preferences about pain-related matters can prompt physicians to change their pain management regimen , which in turn may lead to better pain control . Future research should model pathways through which clinician-patient communication can lead to better cancer outcomes PURPOSE To describe a r and omized trial of a cognitive behavioral intervention on reducing symptom severity among patients diagnosed with solid tumors and undergoing a first course of chemotherapy and to determine whether the intervention had an additive or interactive effect on symptom severity in the presence of supportive care medications . PATIENTS AND METHODS Patients ( N = 237 ) were accrued from comprehensive and community cancer centers , interviewed , and r and omly assigned to either the experimental intervention ( n = 118 ) or conventional care ( n = 119 ) . A symptom severity index , based on summed severity scores across 15 symptoms , was the primary outcome . Each patient 's site of cancer , stage at diagnosis , chemotherapy protocol s , and use of supportive medications were learned from medical records . RESULTS Groups were equivalent at baseline , and attrition by characteristics by group was not different . The proportion of patients not receiving chemotherapy at 10 and 20 weeks did not differ by group . At the 10- and 20-week observations , there was a significant interaction between the experimental group and baseline symptom severity . Patients in the experimental group who entered the trial with higher symptom severity reported significantly lower severity at 10 and 20 weeks . Controlling for chemotherapy treatment status at follow-up and supportive care medications did not alter the effect of the experimental intervention . CONCLUSION Compared with conventional care alone , the experimental intervention was effective among patients who entered the trial with higher levels of symptom severity . Age , sex , site or stage of cancer , and supportive medications did not modify the effect of this cognitive behavioral intervention on symptom severity Background The electronic self report assessment - cancer ( ESRA-C ) , has been shown to reduce symptom distress during cancer therapy The purpose of this analysis was to evaluate aspects of how the ESRA-C intervention may have result ed in lower symptom distress ( SD ) . Methods Patients at two cancer centers were r and omized to ESRA-C assessment only ( control ) or the Web-based ESRA-C intervention delivered to patients ’ homes or to a tablet in clinic . The intervention allowed patients to self-monitor symptom and quality of life ( SxQOL ) between visits , receive self-care education and coaching to report SxQOL to clinicians . Summaries of assessment s were delivered to clinicians in both groups . Audio-recordings of clinic visits made 6 weeks after treatment initiation were coded for discussion s of 26 SxQOL issues , focusing on patients ’ /caregivers ’ coached verbal reports of SxQOL severity , pattern , alleviating/aggravating factors and requests for help . Among issues identified as problematic , two measures were defined for each patient : the percent SxQOL reported that included a coached statement , and an index of verbalized coached statements per SxQOL . The Wilcoxon rank test was used to compare measures between groups . Clinician responses to problematic SxQOL were compared . A mediation analysis was conducted , exploring the effect of verbal reports on SD outcomes . Results 517 ( 256 intervention ) clinic visits were audio-recorded . General discussion of problematic SxQOL was similar in both groups . Control group patients reported a median 75 % of problematic SxQOL using any specific coached statement compared to a median 85 % in the intervention group ( p = .0009 ) . The median report index of coached statements was 0.25 for the control group and 0.31 for the intervention group ( p = 0.008 ) . Fatigue , pain and physical function issues were reported significantly more often in the intervention group ( all p < .05 ) . Clinicians ' verbalized responses did not differ between groups . Patients ' verbal reports did not mediate final SD outcomes ( p = .41 ) . Conclusions Adding electronically-delivered , self-care instructions and communication coaching to ESRA-C promoted specific patient descriptions of problematic SxQOL issues compared with ESRA-C assessment alone . However , clinician verbal responses were no different and subsequent symptom distress group differences were not mediated by the patients ' reports . Trial registration NCT00852852 ; 26 Feb PURPOSE Although patient-reported cancer symptoms and quality -of-life issues ( SQLIs ) have been promoted as essential to a comprehensive assessment , efficient and efficacious methods have not been widely tested in clinical setting s. The purpose of this trial was to determine the effect of the Electronic Self-Report Assessment -Cancer ( ESRA-C ) on the likelihood of SQLIs discussed between clinicians and patients with cancer in ambulatory clinic visits . Secondary objectives included comparison of visit duration between groups and usefulness of the ESRA-C as reported by clinicians . PATIENTS AND METHODS This r and omized controlled trial was conducted in 660 patients with various cancer diagnoses and stages at two institutions of a comprehensive cancer center . Patient-reported SQLIs were automatically displayed on a graphical summary and provided to the clinical team before an on-treatment visit ( n = 327 ) ; in the control group , no summary was provided ( n = 333 ) . SQLIs were scored for level of severity or distress . One on-treatment clinic visit was audio recorded for each participant and then scored for discussion of each SQLI . We hypothesized that problematic SQLIs would be discussed more often when the intervention was delivered to the clinicians . RESULTS The likelihood of SQLIs being discussed differed by r and omized group and depended on whether an SQLI was first reported as problematic ( P = .032 ) . Clinic visits were similar with regard to duration between groups , and clinicians reported the summary as useful . CONCLUSION The ESRA-C is the first electronic self-report application to increase discussion of SQLIs in a US r and omized clinical trial 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 CONTEXT Pain and depression are 2 of the most prevalent and treatable cancer-related symptoms , yet they frequently go unrecognized , undertreated , or both . OBJECTIVE To determine whether central ized telephone-based care management coupled with automated symptom monitoring can improve depression and pain in patients with cancer . DESIGN , SETTING , AND PATIENTS R and omized controlled trial conducted in 16 community-based urban and rural oncology practice s involved in the Indiana Cancer Pain and Depression ( INCPAD ) trial . Recruitment occurred from March 2006 through August 2008 and follow-up concluded in August 2009 . The participating patients had depression ( Patient Health Question naire-9 score > or = 10 ) , cancer-related pain ( Brief Pain Inventory [ BPI ] worst pain score > or = 6 ) , or both . INTERVENTION The 202 patients r and omly assigned to receive the intervention and 203 to receive usual care were stratified by symptom type . Patients in the intervention group received central ized telecare management by a nurse-physician specialist team coupled with automated home-based symptom monitoring by interactive voice recording or Internet . MAIN OUTCOME MEASURES Blinded assessment at baseline and at months 1 , 3 , 6 , and 12 for depression ( 20-item Hopkins Symptom Checklist [ HSCL-20 ] ) and pain ( BPI ) severity . RESULTS Of the 405 participants enrolled in the study , 131 had depression only , 96 had pain only , and 178 had both depression and pain . Of the 274 patients with pain , 137 patients in the intervention group had greater improvements in BPI pain severity over the 12 months of the trial whether measured as a continuous severity score or as a categorical pain responder ( > or = 30 % decrease in BPI ) than the 137 patients in the usual-care group ( P < .001 for both ) . Similarly , of the 309 patients with depression , the 154 patients in the intervention group had greater improvements in HSCL-20 depression severity over the 12 months of the trial whether measured as a continuous severity score or as a categorical depression responder ( > or = 50 % decrease in HSCL ) than the 155 patients in the usual care group ( P < .001 for both ) . The st and ardized effect size for between-group differences at 3 and 12 months was 0.67 ( 95 % confidence interval [ CI ] , 0.33 - 1.02 ) and 0.39 ( 95 % CI , 0.01 - 0.77 ) for pain , and 0.42 ( 95 % CI , 0.16 - 0.69 ) and 0.41 ( 95 % CI , 0.08 - 0.72 ) for depression . CONCLUSION Central ized telecare management coupled with automated symptom monitoring result ed in improved pain and depression outcomes in cancer patients receiving care in geographically dispersed urban and rural oncology practice s. TRIAL REGISTRATION clinical trials.gov Identifier : NCT00313573 The purpose of this r and omized controlled community trial is to Output:	Narrative synthesis suggested that feedback of PROM data tended to increase discussion s between patients and professionals about pain and /or symptoms overall . Conclusions Interventions that assess and feedback cancer pain data to patients and /or professionals have so far led to modest reductions in cancer pain intensity .
MS21860	*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 assess the efficacy and safety of intravaginal estriol administration on urinary incontinence , urogenital atrophy , and recurrent urinary tract infections in postmenopausal women . Design Eighty-eight postmenopausal women with urogenital aging symptoms were enrolled in this prospect i ve , r and omized , placebo-controlled study . Participants were r and omly divided into two groups , with each group consisting of 44 women . Women in the treatment group received intravaginal estriol ovules : 1 ovule ( 1 mg ) once daily for 2 weeks and then 2 ovules once weekly for a total of 6 months as maintenance therapy . Women in the control group received inert placebo vaginal suppositories in a similar regimen . We evaluated urogenital symptomatology , urine cultures , colposcopic findings , urethral cytologic findings , urethral pressure profiles , and urethrocystometry before as well as after 6 months of treatment . Results After therapy , the symptoms and signs of urogenital atrophy significantly improved in the treatment group in comparison with the control group . Thirty ( 68 % ) of the treated participants , and only seven ( 16 % ) of the control participants registered a subjective improvement of their incontinence . In the treated participants , we observed significant improvements of colposcopic findings , and there were statistically significant increases in mean maximum urethral pressure , in mean urethral closure pressure as well as in the abdominal pressure transmission ratio to the proximal urethra . Urethrocystometry showed positive but not statistically significant modifications . Conclusions Our results show that intravaginal administration of estriol may represent a satisfactory therapeutic choice for those postmenopausal women with urogenital tract disturbances who have contraindications or refuse to undergo st and ard hormone therapy Abstract Purpose To assess the effects of the combination of pelvic floor rehabilitation , intravaginal estriol and Lactobacillus acidophli administration on stress urinary incontinence ( SUI ) , urogenital atrophy and recurrent urinary tract infections in postmenopausal women . Methods 136 postmenopausal women with urogenital aging symptoms were enrolled in this prospect i ve r and omized study . Patients : r and omly divided into two groups and each group consisted of 68 women . Interventions : Subjects in the triple therapy ( group I ) received 1 intravaginal ovule containing 30 mcg estriol and Lactobacilli acidophili ( 50 mg lyophilisate containing at least 100 million live bacteria ) such as once daily for 2 weeks and then two ovules once weekly for a total of 6 months as maintenance therapy plus pelvic floor rehabilitation . Subjects in the group II received one intravaginal estriol ovule ( 1 mg ) plus pelvic floor rehabilitation in a similar regimen . Mean outcome measures : We evaluated urogenital symptomatology , urine cultures , colposcopic findings , urethral cytologic findings , urethral pressure profiles and urethrocystometry before , as well as after 6 months of treatment . Results After therapy , the symptoms and signs of urogenital atrophy significantly improved in both groups . 45/59 ( 76.27 % ) of the group I and 26/63 ( 41.27 % ) of the group II referred a subjective improvement of their incontinence . In the patients treated by triple therapy with lactobacilli , estriol plus pelvic floor rehabilitation , we observed significant improvements of colposcopic findings , and there were statistically significant increases in mean maximum urethral pressure , in mean urethral closure pressure , as well as in the abdominal pressure transmission ratio to the proximal urethra . Conclusions Our results showed that triple therapy with L. acidophili , estriol plus pelvic floor rehabilitation was effective and should be considered as first-line treatment for symptoms of urogenital aging in postmenopausal women We compared the efficacy and safety of estriol-containing vaginal pessary use with those of oral nitrofurantoin macrocrystal ( NM ) therapy for preventing urinary tract infection ( UTI ) in postmenopausal women with recurrent UTI . Over a period of 9 months , 86 women received an estriol-containing vaginal pessary ( 0.5 mg estriol ) twice weekly , and 85 women received NM ( 100 mg ) once daily . We recorded 124 episodes of UTI in women who received estriol-releasing pessaries and 48 episodes of UTI in women treated with NM ( P=.0003 ) . Twenty-eight women ( 32.6 % ) who received estriol had no episodes of UTI versus 41 women ( 48.2 % ) in the NM group . There was a significant increase in the number of superficial cells in women who received estriol , whereas in the NM group , no such changes occurred . However , there was no change in the extent of Lactobacillus colonization and in the vaginal pH in women who received estriol . Use of an estriol-containing pessary is less effective than oral NM therapy in the prevention of bacteriuria in postmenopausal women because of its failure to restore the population of lactobacilli and to reduce the vaginal pH in these women OBJECTIVE The primary objective was to detect a difference in time until the first recurrence of urinary tract infection during treatment with an estradiol-releasing silicone vaginal ring ( Estring ; Pharmacia & Upjohn , Inc , Uppsala , Sweden ) compared with no estrogen treatment . The secondary objective was to detect any differences in improvement of urethral and vaginal mucosal atrophy and in the subjective assessment of urogenital symptoms . The study also sought to detect a difference in decrease of vaginal pH to < 5.5 and to record adverse events . STUDY DESIGN This was a multicenter , r and omized , open , parallel-group study with an untreated control group . Postmenopausal women with recurrent symptomatic , bacteriologically confirmed urinary tract infections were r and omly assigned to receive either Estring ( 2 mg estradiol ) or no estrogen treatment . One ring was carried vaginally for 12 weeks . The duration of treatment was 36 weeks for the Estring group and either 36 weeks or until the first recurrence for the control group . Both intent-to-treat and per- protocol analyses were performed to evaluate efficacy , whereas the safety analysis was limited to the intent-to-treat group . The primary variable was analyzed by survival analysis with the Kaplan-Meier method for estimating the survival density function . To compare the survival curves for the 2 treatment groups a log-rank test was performed for time until first recurrence . RESULTS A total of 108 women were r and omly assigned , 53 to the Estring group and 55 to the control group . The cumulative proportion of women remaining free of urinary tract infection was significantly higher in the Estring group than in the control group ( P = .008 ) . After 36 weeks of study the cumulative likelihood of remaining free of disease was approximately 45 % in the women with the vaginal ring compared with approximately 20 % in the control group . Estring lowered vaginal pH , and the time to first recurrence was effectively prolonged by Estring treatment . Vaginal and , to a lesser extent , urethral mucosal cells were significantly more mature in the Estring group . No unexpected adverse events were found . CONCLUSION Estring is useful to prolong the time to next recurrence among postmenopausal women with recurrent urinary tract infection and to decrease the number of recurrences per year . The silicone vaginal ring also has a clinical ly significant ability to alleviate other postmenopausal urogenital symptoms . Estring is safe and well tolerated A block r and omized , double-blind , group-comparative , placebo-controlled study was conducted to assess the effect of oestriol on recurrent urinary tract infections in postmenopausal women . 40 women , median age 78 years ( 66 - 91 ) , 20 in each group , were treated with oestriol three mg p.o . per day or corresponding placebo for four weeks , followed by one mg per day for eight weeks . The main response parameter was the number of urinary tract infections per week in the two treatment periods . Both oestriol and placebo reduced the number of infections per week significantly in both periods , compared with the pretreatment period . There was no difference between oestriol and placebo treatment in the first period . In the second period , however , oestriol treatment was significantly more effective than placebo ( p = 0.05 ) . Correspondingly , there was a significant difference between the two groups in the vaginal pH at the end of the study ( p less than 0.05 ) . We conclude that oestriol reduces recurrent urinary tract infections in postmenopausal women BACKGROUND Growing antibiotic resistance warrants study ing nonantibiotic prophylaxis for recurrent urinary tract infections ( UTIs ) . Use of lactobacilli appears to be promising . METHODS Between January 2005 and August 2007 , we r and omized 252 postmenopausal women with recurrent UTIs taking part in a double-blind noninferiority trial to receive 12 months of prophylaxis with trimethoprim-sulfamethoxazole , 480 mg , once daily or oral capsules containing 109 colony-forming units of Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 twice daily . Primary end points were the mean number of symptomatic UTIs , proportion of participants with at least 1 UTI during 12 months , time to first UTI , and development of antibiotic resistance by Escherichia coli . RESULTS The mean number of symptomatic UTIs in the year preceding r and omization was 7.0 in the trimethoprim-sulfamethoxazole group and 6.8 in the lactobacilli group . In the intention-to-treat analysis , after 12 months of prophylaxis , these numbers were 2.9 and 3.3 , respectively . The between-treatment difference of 0.4 UTIs per year ( 95 % CI , -0.4 to 1.5 ) was outside our noninferiority margin . At least 1 symptomatic UTI occurred in 69.3 % and 79.1 % of the trimethoprim-sulfamethoxazole and lactobacilli participants , respectively ; median times to the first UTI were 6 and 3 months , respectively . After 1 month of trimethoprim-sulfamethoxazole prophylaxis , resistance to trimethoprim-sulfamethoxazole , trimethoprim , and amoxicillin had increased from approximately 20 % to 40 % to approximately 80 % to 95 % in E coli from the feces and urine of asymptomatic women and among E coli causing a UTI . During the 3 months after trimethoprim-sulfamethoxazole discontinuation , resistance levels gradually decreased . Resistance did not increase during lactobacilli prophylaxis . CONCLUSIONS In postmenopausal women with recurrent UTIs , L rhamnosus GR-1 and L reuteri RC-14 do not meet the noninferiority criteria in the prevention of UTIs when compared with trimethoprim-sulfamethoxazole . However , unlike trimethoprim-sulfamethoxazole , lactobacilli do not increase antibiotic resistance . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N50717094 BACKGROUND Recurrent urinary tract infections are a problem for many postmenopausal women . Estrogen replacement restores atrophic mucosa , lowers vaginal pH , and may prevent urinary tract infections . METHODS We enrolled 93 postmenopausal women with a history of recurrent urinary tract infections in a r and omized , double-blind , placebo-controlled trial of a topically applied intravaginal estriol cream . Midstream urine cultures were obtained at enrollment , monthly for eight months , and whenever urinary symptoms occurred . Vaginal cultures and pH measurements were obtained at entry and after one and eight months . The women were assigned to receive either estriol ( n = 50 ) or placebo ( n = 43 ) , both administered intravaginally ; 36 and 24 , respectively , completed the eight months of follow-up . RESULTS The incidence of urinary tract infection in the group given estriol was significantly reduced as compared with that in the group given placebo ( 0.5 vs. 5.9 episodes per patient-year , P < 0.001 ) . Survival analysis showed that more of the women in the estriol group than in the placebo group remained free of urinary tract infection ( P < 0.001 ) . Lactobacilli were absent in all vaginal cultures before treatment and reappeared after one month in 22 of 36 estriol-treated women ( 61 percent ) but in none of the 24 placebo recipients ( P < 0.001 ) . With estriol the mean vaginal pH declined from 5.5 to 3.8 ( P < 0.001 ) , whereas there was no significant change with placebo . The rate of vaginal colonization with Enterobacteriaceae fell from 67 percent to 31 percent in estriol recipients but was virtually unchanged ( from 67 to 63 percent ) in the placebo recipients ( P < 0.005 ) . Side effects were minor , but caused 10 estriol recipients ( 28 percent ) and 4 placebo recip Output:	Antibiotics were the most efficacious therapy but with a higher incidence of systemic side effects . Vaginal estrogen appeared to be inferior to continuous oral antibiotic suppression ; however , use of multiple formulations of both treatment options precludes meta- analysis . This review supports the use of antibiotic suppression , vaginal estrogen , and oral lactobacillus for prevention of recurrent UTIs in postmenopausal women . However , the overall dearth of data suggests that this is an important but understudied population .
MS21861	*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 purpose of this study was to determine whether strength training could reduce the deficit in plantarflexion ( PF ) maximal voluntary contraction ( MVC ) torque observed in previous studies in older subjects relative to young adults . Accordingly , the effects of a 6-month strength training program on the muscle and neural properties of the major muscle groups around the ankle were examined . PF and dorsiflexion ( DF ) isometric MVC torques were measured and surface electromyographic activity of the triceps surae and tibialis anterior muscles was recorded . The strength training program was very effective in improving strength in PF ( + 24.5 % ) , and it thus reduced the DF-to-PF MVC torque ratio ; in addition , it also induced gains in DF ( + 7.6 % ) . Thus , there must be an improvement in ankle joint stability . In PF , gains were due particularly to a modification of the agonist neural drive ; in DF , the gains appeared to be the consequence of a reduction in antagonist coactivation . Our findings indicate that the investigation of one muscle group should always be accompanied by examination of its antagonist muscle group Effects of 6 mo of heavy-resistance training combined with explosive exercises on neural activation of the agonist and antagonist leg extensors , muscle cross-sectional area ( CSA ) of the quadriceps femoris , as well as maximal and explosive strength were examined in 10 middle-aged men ( M40 ; 42 + /- 2 yr ) , 11 middle-aged women ( W40 ; 39 + /- 3 yr ) , 11 elderly men ( M70 ; 72 + /- 3 yr ) and 10 elderly women ( W70 ; 67 + /- 3 yr ) . Maximal and explosive strength remained unaltered during a 1-mo control period with no strength training . After the 6 mo of training , maximal isometric and dynamic leg-extension strength increased by 36 + /- 4 and 22 + /- 2 % ( P < 0 . 001 ) in M40 , by 36 + /- 3 and 21 + /- 3 % ( P < 0.001 ) in M70 , by 66 + /- 9 and 34 + /- 4 % ( P < 0.001 ) in W40 , and by 57 + /- 10 and 30 + /- 3 % ( P < 0.001 ) in W70 , respectively . All groups showed large increases ( P < 0.05 - 0.001 ) in the maximum integrated EMGs ( iEMGs ) of the agonist vastus lateralis and medialis . Significant ( P < 0.05 - 0.001 ) increases occurred in the maximal rate of isometric force production and in a squat jump that were accompanied with increased ( P < 0.05 - 0 . 01 ) iEMGs of the leg extensors . The iEMG of the antagonist biceps femoris muscle during the maximal isometric leg extension decreased in both M70 ( from 24 + /- 6 to 21 + /- 6 % ; P < 0.05 ) and in W70 ( from 31 + /- 9 to 24 + /- 4 % ; P < 0.05 ) to the same level as recorded for M40 and W40 . The CSA of the quadriceps femoris increased in M40 by 5 % ( P < 0.05 ) , in W40 by 9 % ( P < 0.01 ) , in W70 by 6 % ( P < 0.05 ) , and in M70 by 2 % ( not significant ) . Great training-induced gains in maximal and explosive strength in both middle-aged and elderly subjects were accompanied by large increases in the voluntary activation of the agonists , with significant reductions in the antagonist coactivation in the elderly subjects . Because the enlargements in the muscle CSAs in both middle-aged and elderly subjects were much smaller in magnitude , neural adaptations seem to play a greater role in explaining strength and power gains during the present strength-training protocol Twenty sedentary male university students were r and omly assigned to an experimental or a control group . The experimental group trained the knee extensors of one leg by producing 30 isometric extension maximal voluntary contractions ( MVC ) per day , three times per week for 8 wk . After 8 wk of training , extensor MVC in the trained leg increased 32.8 % ( P less than 0.05 ) , but there was no change in vastus lateralis maximal integrated electromyographic activity ( IEMGmax ) . The most important finding was that the degree of hamstring coactivation during extension MVC decreased by approximately 20 % ( P less than 0.05 ) after the 1st wk of training . Less pronounced adaptations occurred in the untrained leg : extension MVC force increased 16.2 % ( P less than 0.05 ) , hamstring coactivity decreased 13 % ( P less than 0.05 ) after 2 wk of training , and vastus lateralis IEMGmax was unchanged . The same measures in legs of the control group were not changed during the study . There were no changes in flexion MVC , biceps femoris IEMGmax , or the degree of quadriceps coactivity during flexion MVC in either leg of the control or experimental group . A reduction in hamstring coactivity in the trained and untrained legs indicates that these muscles provide less opposing force to the contracting quadriceps . We conclude that this small but significant decrease in hamstring coactivation that occurs during the early stages of training is a nonhypertrophic adaptation of the neuromuscular system in response to static resistance training of this type We compared the effect of a 10‐week resistance training program on peak isometric torque , muscle hypertrophy , voluntary activation and electromyogram signal amplitude ( EMG ) of the knee extensors between young and elderly women . Nine young women ( YW ; range 20–30 years ) and eight elderly women ( EW ; 64–78 years ) performed three sets of ten repetitions at 75 % 1 repetition maximum for the bilateral leg extension and bilateral leg curl 3 days per week for 10 weeks . Peak isometric torque , EMG and voluntary activation were assessed before , during , and after the training period , while knee extensor lean muscle cross‐sectional area ( LCSA ) and lean muscle volume ( LMV ) were assessed before and after the training period only . Similar increases in peak isometric torque ( 16 % and 18 % ) , LCSA ( 13 % and 12 % ) , LMV ( 10 % and 9 % ) and EMG ( 19 % and 21 % ) were observed between YW and EW , respectively , at the completion of training ( P<0·05 ) , while the increase in voluntary activation in YW ( 1·9 % ) and EW ( 2·1 % ) was not significant ( P>0·05 ) . These findings provide evidence to indicate that participation in regular resistance exercise can have significant neuromuscular benefits in women independent of age . The lack of change in voluntary activation following resistance training in both age groups despite the increase in EMG may be related to differences between measurements in their ability to detect resistance training‐induced changes in motor unit activity . However , it is possible that neural adaptation did not occur and that the increase in EMG was due to peripheral adaptations The aim of this study was to enquire whether older adults , who continue plantar-flexion ( PF ) strength training for an additional 6-month period , would achieve further improvements in neuromuscular performance , in the ankle PFs , and in the antagonist dorsi-flexors ( DFs ) . Twenty-three healthy older volunteers ( mean age 77.4 ± 3.7 years ) took part in this investigation and 12 of them followed a 1-year strength-training program . Both neural and muscular factors were examined during isometric maximal voluntary contraction ( MVC ) torques in ankle PF and DF pre-training , post 6 and post 12 months . The main finding was that 6 months of additional strength training of the PFs , beyond 6 months , allowed further improvements in neuromuscular performance at the ankle joint in older adults . Indeed , during the first 6 months of progressive resistance training , there was an increase in the PF MVC torque of 11.1 ± 19.9 N m , and then of 11.1 ± 17.9 N m in the last 6-month period . However , it was only after 1 year that there was an improvement in the evoked contraction at rest in PF ( + 8 % ) . The strength training of the agonist PF muscles appeared to have an impact on the maximal result ant torque in DF . However , it appeared that this gain was first due to modifications occurring in the trained PFs muscles , then , it seemed that the motor drive of the DFs per se was altered . In conclusion , long-term strength training of the PFs result ed in continued improvements in neuromuscular performance at the ankle joint in older adults , beyond the initial 6 months 1 . The adaptations of the ankle dorsiflexor muscles and the behaviour of single motor units in the tibialis anterior in response to 12 weeks of dynamic training were studied in five human subjects . In each training session ten series of ten fast dorsiflexions were performed 5 days a week , against a load of 30 - 40 % of the maximal muscle strength . 2 . Training led to an enhancement of maximal voluntary muscle contraction ( MVC ) and the speed of voluntary ballistic contraction . This last enhancement was mainly related to neural adaptations since the time course of the muscle twitch induced by electrical stimulation remained unaffected . 3 . The motor unit torque , recorded by the spike-triggered averaging method , increased without any change in its time to peak . The orderly motor unit recruitment ( size principle ) was preserved during slow ramp contraction after training but the units were activated earlier and had a greater maximal firing frequency during voluntary ballistic contractions . In addition , the high frequency firing rate observed at the onset of the contractions was maintained during the subsequent spikes after training . 4 . Dynamic training induced brief ( 2 - 5 ms ) motor unit interspike intervals , or ' doublets ' . These doublets appeared to be different from the closely spaced ( + /-10 ms ) discharges usually observed at the onset of the ballistic contractions . Motor units with different recruitment thresholds showed doublet discharges and the percentage of the sample of units firing doublets was increased by training from 5.2 to 32.7 % . The presence of these discharges was observed not only at the onset of the series of spikes but also later in the electromyographic ( EMG ) burst . 5 . It is likely that earlier motor unit activation , extra doublets and enhanced maximal firing rate contribute to the increase in the speed of voluntary muscle contraction after dynamic training Explosive-type strength training may alter kinetics and neuromuscular activity during stair ascent in elderly women . This may improve functional ability . Nineteen women ( 69.7 ± 3.4 yr ) were r and omly allocated to strength training ( TG ; twice per wk , 12 wk ) or a control group ( CG ) . Stair ascent was assessed at self-chosen ( AFV ) , st and ardized ( ASV ) , and maximal velocity ( AMV ) pre- and posttraining . Ground-reaction force ( GRF ) and EMG quantified kinetics and neuromuscular activity . After training , TG increased AMV and AFV velocity by 8 % ( p = .02 ) and 17 % ( p= .007 ) , respectively ( TG vs. CG ; p < .05 ) . This was accompanied by elevated rectus femoris EMG ( from 21 % to 48 % , p < .047 ) . At AFV , TG increased GRF first peak force 4 % ( p= .047 ) , and CG increased second peak force 5 % ( p = .036 ) . Muscle coactivation remained unaltered in both groups . Explosive-type strength training led to enhanced stair-climbing performance at maximal and self-chosen speed , reflecting an improved functional ability PURPOSE To test the ability of a combination high-velocity/high-resistance training program to enhance knee extensor muscle strength , power , nervous activation of muscle , and muscle activation time in inactive women and compare the response to training between young and old women . METHODS The study involved 49 inactive women , with young ( 18 - 33 yr , n = 25 ) and old ( 65 - 84 yr , n = 24 ) distributed to training and control groups using blocked r and omization . Electrically evoked muscle twitches were measured for the knee extensors ; then maximal , voluntary , isometric knee extensions were performed in a visually cued reaction time ( RT ) task , followed by 8 wk of explosive resistance training . RESULTS Training increased peak torque ( + 12 % , P = 0.03 ) and reduced antagonist coactivation ( -13 % , P = 0.02 ) similarly for both age groups . Young training group increased the rate of torque development by 34 % compared to young controls ( -7 % ) , old training ( + 9 % ) , and old controls ( + 8 % ) ( P = 0.002 ) . Young training group increased impulse by 53 % , which was greater than young controls ( -11 % ) , old training ( + 12 % ) , and old controls ( + 9 % ) ( P = 0.001 ) . Resistance training did not change electrically evoked twitch , RT ( premotor time , motor time , or reaction time ) , or nervous activation measures ( onset EMG amplitude or rate of EMG rise ) . CONCLUSIONS Explosive force training was ineffective at enhancing muscle twitch characteristics , neural drive , or RT in young or old women . It did enhance peak muscle force in both young and old , modulated through a reduction in antagonist coactivation . Older participants showed less of an improvement in the rate of torque development and contractile impulse than young , indicating either that this sample of older women had a reduced capacity to develop muscle Output:	Based on our results we can conclude that there is evidence for exercise-induced increase in voluntary activation related to strength gains in the lower extremities in elderly persons .
MS21862	*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: Neuropsychological ( mostly posterior-cortical ) deficits , quantitative magnetic resonance imaging ( MRI ) atrophy patterns , and low cerebrospinal fluid ( CSF ) levels of amyloid-β have been separately related to worsening cognition in Parkinson 's disease ( PD ) . However , these biomarkers have not been longitudinally assessed in combination as PD-dementia predictors . In this prospect i ve longitudinal study , 27 non-demented PD patients underwent CSF , neuropsychological and 3-T brain-MRI studies at baseline and were re-assessed 18 months later in terms of progression to dementia ( primary outcome ) and longitudinal neuropsychological and cortical thickness changes ( secondary outcomes ) . At follow-up 11 patients ( 41 % ) had progressed to dementia . Lower CSF amyloid-β , worse verbal learning , semantic fluency and visuoperceptual scores , and thinner superior-frontal/anterior cingulate and pre central regions were significant baseline dementia predictors in binary logistic regressions as quantitative and /or dichotomised traits . All participants without baseline biomarker abnormalities remained non-demented whereas all with abnormalities in each biomarker type progressed to dementia , with intermediate risk for those showing abnormalities in a single to two biomarker types ( p = 0.006 ) . Both the dementia- outcome and low baseline CSF amyloid-β were prospect ively associated with limbic and posterior-cortical neuropsychological decline and frontal , limbic and posterior-cortical thinning from baseline to follow-up . These findings suggest that the combination of CSF amyloid-β , neuropsychological and cortical thickness biomarkers might provide a basis for dementia-risk stratification and progression monitoring in PD Objective : To test in vivo the proposal from clinicopathologic studies that β-amyloid ( Aβ ) pathology shortens the time to dementia in Parkinson disease ( PD ) , and to explore the utility of CSF Aβ and related measures as early prognostic biomarkers of dementia in an incident PD cohort . Methods : We assessed a population -based incident cohort of 104 patients with PD who underwent lumbar puncture at diagnosis . We analyzed CSF concentrations of Aβ42 , Aβ40 , and Aβ38 using a multiplexed immunoassay with electrochemiluminescence ( ECL ) detection and levels of Aβ42 , total tau , and phosphorylated tau using ELISA . Patients were followed prospect ively for 5 years . Dementia was diagnosed according to published criteria . Results : CSF levels of Aβ42 were significantly decreased in patients who developed dementia ( n = 20 , 19.2 % ) compared to those who did not ( n = 84 , 80.8 % ) , as measured by ECL ( −33 % , p = 0.006 ) as well as ELISA ( −36 % , p < 0.001 ) . No differences were observed for other markers . Low Aβ42 values predicted a substantially increased risk for subsequent dementia at high sensitivity ( ≥85 % ) , with hazard ratios of 9.9 ( 95 % confidence interval 2.3–43.5 , p = 0.002 ) for Aβ42ECL < 376 pg/mL and 7.6 ( 2.2–26.4 , p = 0.001 ) for Aβ42ELISA < 443 pg/mL , after adjustment for baseline age and PD – mild cognitive impairment ( MCI ) status . Aβ42 reductions tended to precede the onset of PD-MCI that progressed to dementia . Conclusions : These in vivo data support the role of Aβ pathology in the etiology and highlight the potential utility of CSF Aβ42 as an early prognostic biomarker of dementia associated with PD Few detailed clinico-pathological correlations of Parkinson 's disease have been published . The pathological findings in 100 patients diagnosed prospect ively by a group of consultant neurologists as having idiopathic Parkinson 's disease are reported . Seventy six had nigral Lewy bodies , and in all of these Lewy bodies were also found in the cerebral cortex . In 24 cases without Lewy bodies , diagnoses included progressive supranuclear palsy , multiple system atrophy , Alzheimer 's disease , Alzheimer-type pathology , and basal ganglia vascular disease . The retrospective application of recommended diagnostic criteria improved the diagnostic accuracy to 82 % . These observations call into question current concepts of Parkinson 's disease as a single distinct morbid entity Cerebrospinal fluid ( CSF ) biomarkers for Alzheimer ’s disease ( AD ) reflect brain biochemistry . Using combined immunoprecipitation and mass spectrometry , we have shown that amyloid beta 1 - 15 ( Aβ1 - 15 ) is produced by concerted β- and α-secretase cleavage of amyloid precursor protein ( APP ) and that the relative levels of Aβ1 - 16 in AD compared to controls are increased . Furthermore , drug-induced γ-secretase inhibition enhances the relative levels of Aβ1 - 15 and Aβ1 - 16 . Here , we investigate a novel immunoassay for Aβ1 - 15/16 in a broad range of neurodegenerative conditions . The CSF level of Aβ1 - 15/16 was measured by the bead-based amplified luminescent proximity homogeneous assay ( Alpha technology ) . Concentrations of Aβ1 - 15/16 were analyzed in subjects with Parkinson disease ( PD ; n = 90 ) , PD with dementia ( PDD ) ( n = 32 ) , dementia with Lewy bodies ( DLB ) ( n = 68 ) , AD ( n = 48 ) , progressive supranuclear palsy ( PSP ) ( n = 45 ) , multiple system atrophy ( MSA ) ( n = 46 ) , and corticobasal degeneration ( CBD ) ( n = 12 ) . The detecting antibody is specific to the C-terminal epitope of Aβ15 . We found that a carboxypeptidase ( CPB ) present in fetal bovine serum ( FBS ) , a component of the buffers used , de grade s Aβ1 - 16 to Aβ1 - 15 , which is then detected by the Aβ1 - 15/16 assay . Significantly , lower levels of Aβ1 - 15/16 were detected in PD , PDD , PSP , and MSA compared to other neurodegenerative diseases and controls . Using the specific Aβ1 - 15/16 assay , a reliable quantification of Aβ1 - 15 or Aβ1 - 15/16 in CSF sample s is obtained . We found reduced levels of Aβ1 - 15 in parkinsonian disease groups . The molecular mechanism behind this reduction is at present unknown Differential diagnosis between Parkinson 's disease ( PD ) and multiple system atrophy ( MSA ) is difficult , particularly at early disease stages , but is important for therapeutic management . The protein DJ-1 is implicated in the pathology of PD but little is known about its involvement in MSA . We aim ed to determine the diagnostic value of CSF DJ-1 and tau proteins for discriminating PD and MSA . DJ-1 and total tau levels were quantified in the CSF of 43 PD patients , 23 MSA patients and 30 non-neurological controls matched for age and gender . Patients were part of a study with a 3-year prospect i ve design with extended case- review follow-up of up to 9 years , ensuring maximum accuracy of the clinical diagnosis . Our results showed that CSF DJ-1 levels could distinguish MSA from PD with a 78 % sensitivity and 78 % specificity ( AUC = 0.84 ) . The combination of DJ-1 and tau proteins significantly improved this discrimination to 82 % sensitivity and 81 % specificity to identify MSA from PD ( AUC = 0.92 ) . Our results highlight the potential benefits of a combination of DJ-1 and total tau as biomarkers for differential diagnosis of MSA and PD In order to investigate the possible role of oxidative RNA damage in the pathogenesis of Parkinson 's disease ( PD ) , the concentrations of the oxidative stress marker 8-hydroxyguanosine ( 8-OHG ) were measured in the cerebrospinal fluid ( CSF ) and the serum of patients with PD and control subjects . The concentration of 8-OHG in CSF in PD patients was approximately three-fold that in controls ( P < 0.001 ) . The concentration of 8-OHG in CSF decreased significantly with the duration of disease ( r(s ) = -0.46 , P < 0.05 ) . However , the concentration of 8-OHG in serum was not significantly altered in PD patients compared to that in controls . In addition , the concentration of 8-OHG in CSF showed no correlation with that in serum in both the controls and PD patients suggesting that the 8-OHG concentrations in the CSF do not reflect those in serum and may be probably reflect those in brain tissue . These in vivo findings suggest a possible role of 8-OHG and increased oxidative RNA damage in the early stage of the development of PD Objective : Cognitive decline associated with Parkinson disease ( PD ) is common and highly disabling . Biomarkers that help identify patients at risk for cognitive decline would be useful additions to the clinical management of the disease . Methods : A total of 45 patients with PD were enrolled in this prospect i ve cohort study and had at least 1 yearly longitudinal follow-up evaluation . CSF was collected at baseline and cognition was assessed at baseline and follow-up visits using the Mattis Dementia Rating Scale ( DRS-2 ) . CSF was tested for amyloid β 1 - 42 ( Aβ1 - 42 ) , p-tau181p , and total tau levels using the Luminex xMAP platform . Mixed linear models were used to test for associations between baseline CSF biomarker levels and change in cognition over time . Results : Lower baseline CSF Aβ1 - 42 was associated with more rapid cognitive decline . Subjects with CSF Aβ1 - 42 levels ≤192 pg/mL declined an average of 5.85 ( 95 % confidence interval 2.11–9.58 , p = 0.002 ) points per year more rapidly on the DRS-2 than subjects above that cutoff , after adjustment for age , disease duration , and baseline cognitive status . CSF total tau and p-tau181p levels were not significantly associated with cognitive decline . Conclusions : Reduced CSF Aβ1 - 42 was an independent predictor of cognitive decline in patients with PD . This observation is consistent with previous research showing that Alzheimer disease pathology contributes to cognitive impairment in PD . This biomarker may provide clinical ly useful prognostic information , particularly if combined with other risk factors for cognitive impairment in PD Abstract – DATA TOP is a double‐blind , multi‐center , placebo‐controlled clinical trial aim ed at slowing the decline of patients who are in the early stages of Parkinson 's disease ( PD ) . The specific aim is to determine whether or not chronic administration of deprenyl 10 mg per day and /or tocopherol 2000 IU per day to early , otherwise untreated PD patients will prolong the time until levodopa therapy is required to treat emerging disability . Deprenyl and tocopherol exert antioxidative effects through separate but complementary mechanisms of action . A 2 X 2 factorial design allocates eligible subjects to one of four treatment groups : 1 ) deprenyl alone , 2 ) tocopherol alone , 3 ) deprenyl plus tocopherol , or 4 ) placebo . Eligible subjects include early PD patients ( illness duration less than 5 years and in stages I and II ) , aged 30 to 79 , who are not taking or requiring any anti‐PD medications . The major response variable is the time period from r and omization until the blinded investigator judges levodopa necessary to treat emerging parkinsonian disability . R and omization is stratified to ensure that treatment assignments are balanced for each blinded investigator . Cerebrospinal fluid is sample d just prior to r and omization and one month after washout of experimental medications in order to help distinguish between symptomatic and protective effects of interventions . Based on pilot studies it is estimated that approximately 85 % of untreated PD patients will require levodopa within two years and a total sample size of 800 subjects will provide a 95 % likelihood for detecting a 10 % “ survival'’difference between experimental medications and placebo . Between September 1987 and November 1988 , 800 eligible subjects were enrolled in DATA TOP by 34 investigators of the Parkinson Study Group , representing research centers in the United States and Canada . Primary analyses of DATA TOP should be completed in 1991 Output:	Oligomeric alpha-synuclein might be helpful in the separation of PD from controls . Neurofilament light chain ( NfL ) has a significant role in distinguishing PD from other neurodegenerative diseases . Several oxidative stress markers are related to disease severity , with the antioxidant urate also having a prognostic value in terms of disease severity . Increased levels of amyloid and tau-proteins correlate with cognitive decline and may have prognostic value for cognitive deficits in PD .
MS21863	*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: There is some evidence that rehabilitation therapies may be useful in progressive neurological conditions , but this usefulness has not been studied in multiple system atrophy ( MSA ) to date . The aim of this small pilot study was to identify the feasibility of a larger r and omized controlled trial of occupational therapy and to report preliminary data on the impact of occupational therapy on disability , mood , and health-related quality of life in patients with MSA . Patient groups were comparable for age , gender distribution , type of MSA , and severity . The active occupational therapy intervention group experienced a significant reduction of Unified Parkinson 's Disease Rating Scale ( total score and Activities of Daily Living [ ADL ] section ) , and PDQ-39 scores ( total scores and ADL subsection ) . An occupational therapy program may improve functional abilities in patients with mild to moderate MSA . A larger multicenter study is needed BACKGROUND Several previous studies have examined the health of carers , but they have usually focused on elderly subjects and have often not had representative control sample s. AIM To determine whether caring for a partner with Parkinson 's disease is associated with a worsening social , psychological and physical well-being than people with partners who do not suffer with Parkinson 's disease . METHOD One hundred and fifty-four carer spouses of subjects with Parkinson 's disease , and 124 non-carer spouses of r and omly selected population controls recruited from a national case-control study of early-onset Parkinson 's disease in the Republic of Irel and , between 1992 - 1994 , were studied . Outcome was measured along three dimensions : social functioning , assessed by the frequency of social contacts , outings and holidays ; psychological well-being , measured by the General Health Question naire ; and physical health , measured by the career 's use of medical services , medications and episodes of chronic illness . RESULTS Carer spouses were less likely to get out of the house once a week at least ( odds ratio 1.79 , 95 % confidence intervals 1.00 - 3.20 ) or to have had a holiday in the last year ( odds ratio 1.71 , 95 % confidence intervals 1.01 - 2.90 ) . Contact with friends and neighbours decreased with increasing care provision . For spouses providing a lot of care , there was an almost fivefold increase in psychiatric morbidity ( odds ratio 4.86 , 95 % confidence intervals 1.5 - 15.9 ) after adjusting for other variables . Most of the medical outcomes were less favourable among carers , but only the use of tranquilizers ( odds ratio 3.73 , 95 % confidence intervals 1.18 - 11.8 ) and episodes of chronic illness ( odds ratio 2.96 , 95 % confidence intervals 1.27 - 6.94 ) were significant . CONCLUSIONS Overall , career spouses have slightly worse social , psychological and physical profiles . For social outcomes , increasing care provision is associated with fewer contacts , outings and holidays . For psychological and physical measures , carers providing a lot of care experience worse health . These results have implication s for targeting appropriate interventions The medical treatment of idiopathic Parkinson 's disease has improved the quality of life and increased survival of patients with Parkinson 's disease . However , as the illness progresses , impairments in daily living activities occur . A clinical trial for a group rehabilitation program was initiated to maintain the functional status of these patients . The research protocol consisted of a pretreatment evaluation , r and om assignment to experimental or control groups , and posttreatment evaluations after therapy , at 6 months and at 1 year . The results showed that the subjects of the treated experimental group maintained their functional status after 1 year , demonstrated a significant decrease of bradykinesia , and perceived a significant improvement in their psychological well-being . This study confirms the value of an occupational therapy group approach and its benefits to the functional independence , to the improvement of physical and motor symptoms , and to the quality of life of persons with Parkinson 's disease The development and validation of a short and simple measure of perceived health problems is described . Extensive testing with selected groups , including the elderly , the chronically ill , pregnant women , fracture victims , and a r and om sample of the community has established the face , content and criterion validity , and the reliability of the instrument . The Nottingham Health Profile is intended as a st and ardized tool for the survey of health problems in a population , but is equally valid and useful as a means of evaluating the outcome of medical and /or social interventions and as an adjunct to the clinical interview In a controlled clinical study , we investigated the effects of behavioral treatment on postural and gait initiation problems idiopathic Parkinson 's disease ( PD ) . Comparable groups of patients received therapy ( experimental group , n = 15 ) and nonspecific psychological treatment ( control group , n = 14 ) for 10 weeks . We monitored various variables reflecting properties of posture and gait initiation by using an optoelectronic motion analyzer ( electronic movement analysis system , ELITE ) . A clinician blind to group membership of the patients assessed PD severity with the United Parkinson 's Disease Rating Scale ( UPDRS ) before and after the treatment period . ELITE measures of postural stability and movement initiation revealed treatment-specific effects . In addition , UPDRS motor scores showed significant improvement only after behavioral treatment . We conclude that behavioral treatment in Parkinson 's disease may improve motor disabilities in moderately advanced PD patients Objective : To perform a pilot trial of occupational therapy ( OT ) to optimise functional independence in Parkinson disease ( PD ) to assess accrual/withdrawal rates , acceptability , outcome measures , and inform sample -size calculation . Method : Non-demented patients with idiopathic PD and difficulties with activities of daily living ( ADL ) were recruited provided they had not received OT in the last 2 years and /or physiotherapy in the last year . Patients were r and omised to immediate OT or OT after completion of the trial . Patients r and omised to OT were assessed at home by an experienced therapist and then received six home treatment sessions over 2 months . Interventions were targeted at functional independence and mobility goals . Outcome measures were : Nottingham Extended Activity of Daily Living Scale , Rivermead Mobility Index , Unified Parkinson ’s Disease Rating Scale ADL scale , Parkinson ’s Disease Question naire 39 , EuroQol-EQ-5D , Hospital Anxiety and Depression Scale , and health economics analysis . Results : 39 patients ( 25 male ; mean age 73 years ) were recruited from four centres over 16 months . The mean difference in NEADL at 8 months was 3.5 ( 95 % CI −3.2 to 10.2 ) . The mean difference in PDQ-39 Summary Score was 3.8 ( 95 % CI −4.94 to 12.6 ) . There were strong correlations between the PDQ-39 and other outcomes . The intervention was acceptable to patients , with a low withdrawal rate and good question naire completion . Conclusion : R and omisation to a trial of OT in PD is feasible . NEADL and PDQ-39 are relevant outcomes and provided data to inform sample size for an adequately powered r and omised trial for which there is pressing need Objective : To evaluate the effects of weights on postural h and tremor related to self-feeding in subjects with Parkinson 's disease ( PD ) . Design : In a repeated- measures design , postural h and tremor was recorded three times in each of three weight conditions in a single session for each subject . The order of all recording conditions was r and omized . Setting : Intervention was applied and measurement was conducted in a university-based motor performance laboratory . Subjects : Fourteen men and two women diagnosed with PD and having h and tremor participated ( mean age 67.1 years , mean duration of PD 4.6 years ) . All were community-dwelling . Intervention : The control condition consisted of holding a built-up spoon ( 108 g ) . There were two experimental conditions : holding a weighted spoon ( 248 g ) ; and holding the built-up spoon while wearing a weighted wrist cuff ( 470 g ) . Main outcome measures : Three measures of tremor amplitude and two measures of tremor frequency were calculated from recordings of displacement of the spoon obtained from laser displacement sensors . Results : Repeated- measures analyses of variance revealed no signi”cant differences across conditions in any measure of tremor amplitude or in either measure of tremor frequency . Correlational and Mann – Whitney U-test analyses revealed that none of age , disease duration or medication intake had any signi”cant relationship with tremor amplitude in the control condition or with whether amplitude was altered by weights . Conclusions : The ” ndings suggest that there is no support for the clinical recommendation of using weighted utensils or weighted wrist cuffs to alleviate postural h and tremor in PD In a r and omized , single-blind , crossover study , we evaluated physical disability in moderately advanced Parkinson 's disease ( PD ) patients after 4 weeks of normal physical activity and 4 weeks of an intensive physical rehabilitation program . We used a timed motor task and a st and ard assessment of PD severity ( the Unified Parkinson 's Disease Rating Scale [ UPDRS ] with subscales for mentation , activities of daily living [ ADL ] , and motor function ) completed by an investigator blinded to the physical rehabilitation status of the patient . Following physical rehabilitation , there was significant improvement in the UPDRS ADL and motor scores , but no change in mentation score . During the 6 months following physical rehabilitation , patients did not regularly exercise , and the UPDRS scores returned to baseline . We conclude that physical disability in moderately advanced PD objective ly improves with a regular physical rehabilitation program , but this improvement is not sustained when normal activity is resumed Gibberd and others ( 11 April , p 1196 ) and sympathise over the problems they encountered . In a similar controlled trial ' we had difficulty in making due allowance for spontaneous fluctuations in motor performance and concentration which characterise this illness and particularly in assessing the influence of depression and motivation . We had to ab and on attempts to measure the latter factors with appropriate question naires because we often found that the patients fell asleep during assessment . Transport difficulties can prove a major obstacle and tend to influence selection of patients . Exhausting journeys to hospital made some patients underst and ably reluctant to attend twice weekly for outpatient physiotherapy and some became so rigid in anticipation of belated transport that they were unable to leave their home . In addition to organisational difficulties , there seems to be little agreement concerning the principles and methods of physiotherapy appropriate for Parkinsonian disabilities . Nevertheless , we found modest but unequivocal improvement in 10 of 21 patients , and in seven benefit was sustained for at least five weeks after the cessation of treatment . We could not determine whether improvement was physical , psychological , or both . Now that the limitations as well as the potential of antiParkinsonian medication has been determined , clinicians will want to know how best to use diminishing physiotherapy re sources . Clearly there is a need for further trials to clarify these common practical problems of management Ottenbacher KJ , Hinderer SR : Evidence -based practice : methods to evaluate individual patient improvement . Am J Phys Med Rehabil 2001;80:786–796.The expectations and dem and s associated with evidence -based practice in medical rehabilitation require the use of research procedures that are practice based and practitioner oriented . Traditional research methods , including r and omized clinical trials , are powerful techniques for determining the efficacy of rehabilitation interventions ; however , r and omized clinical trials have some practical and ethical limitations when applied to many research questions important to the field of medical rehabilitation , and alternative methods are needed to fully examine the effectiveness of treatment techniques for individual patients and to document clinical accountability . This paper examines the use of single-system design s and N of 1 research strategies . The advantages and limitations of single-system methods are described , and examples relevant to the documentation of clinical outcomes in medical rehabilitation are presented Output:	Although both trials reported a positive effect from occupational therapy , all of the improvements were small . Considering the significant method ological flaws in the studies , the small number of patients examined , and the possibility of publication bias , there is insufficient evidence to support or refute the efficacy of occupational therapy in Parkinson 's disease .
MS21864	*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 : Daivobet ® is a once-daily treatment of psoriasis vulgaris containing betamethasone dipropionate and calcipotriol in a new ointment vehicle . Objective : To assess the cost-effectiveness of once-daily treatment with Daivobet ( 4 weeks ) followed by calcipotriol ( 4 weeks ) compared to tacalcitol ( 8 weeks ) . Methods : Re source utilization was assessed within a double-blind 8-week clinical trial ( all treatments for psoriasis , adverse events and concomitant dermatological medication ) , estimated from the French societal perspective . Results : Total direct medical costs for psoriasis were comparable ( Daivobet : EUR 107.53 and tacalcitol EUR 113.50 ) despite a higher acquisition cost for Daivobet . The probability of ≧75 % reduction in the Psoriasis Area and Severity Index ( effectiveness criterion ) was 46.6 % with Daivobet and 13.9 % with tacalcitol at 4 weeks , and 44.6 and 23.8 % , respectively , at 8 weeks ( both : p < 0.001 ) . Over 8 weeks , Daivobet was almost twice as cost-effective as tacalcitol ( EUR 241.22 per successful treatment vs. EUR 476.70 ) ; this result was robust to sensitivity assumptions . Conclusion : Daivobet is more effective and less costly than tacalcitol for treating psoriasis BACKGROUND Overall assessment s of cost-effectiveness are now commonplace in informing medical policy decision making . It is often important , however , also to investigate how cost-effectiveness varies between patient subgroups . Yet such analyses are rarely undertaken , because appropriate methods have not been sufficiently developed . METHODS We propose a coherent set of Bayesian methods to extend cost-effectiveness analyses to adjust for baseline covariates , to investigate differences between subgroups , and to allow for differences between centres in a multicentre study using a hierarchical model . These methods consider costs and effects jointly , and allow for the typically skewed distribution of cost data . The results are presented as inferences on the cost-effectiveness plane , and as cost-effectiveness acceptability curves . RESULTS In applying these methods to a r and omised trial of case management of psychotic patients , we show that overall cost-effectiveness can be affected by ignoring the skewness of cost data , but that it may be difficult to gain substantial precision by adjusting for baseline covariates . While analyses of overall cost-effectiveness can mask important subgroup differences , crude differences between centres may provide an unrealistic indication of the true differences between them . CONCLUSIONS The methods developed allow a flexible choice for the distributions used for cost data , and have a wide range of applicability -- to both r and omised trials and observational studies . Experience needs to be gained in applying these methods in practice , and using their results in decision making Few studies have compared preference values for health states obtained in different countries . The present study compared Spanish and United Kingdom ( UK ) time trade-off values for EuroQol-5D health states . The same preference elicitation protocol was followed in both countries . Differences in values for 43 health states rated directly were analyzed using t tests , and regression coefficients generated by r and om effects modeling were compared by aggregating the 2 value sets and using dummy variables to analyze country effect by dimension and level of severity . For the milder health states , Spanish and UK value assignation was similar ; for intermediate health states , Spanish values were both higher and lower than UK values , whereas for health states worse than death , UK values were generally higher than Spanish values . There were statistically significant differences ( P < 0.01 ) in values for 34.9 % of health states rated directly , and some preference reversals between countries . UK raters ascribed greater importance to dimensions of pain/discomfort and anxiety/depression , whereas Spanish raters placed more importance on functional dimensions of mobility and self-care . Further analysis is required to determine how these differences affect cost-effectiveness and cost-utility analyses Background —In the Eplerenone Post-Acute Myocardial Infa rct ion Heart Failure Efficacy and Survival Study ( EPHESUS ) , aldosterone blockade with eplerenone decreased mortality in patients with left ventricular systolic dysfunction and heart failure after acute myocardial infa rct ion . The present study was performed to evaluate the cost-effectiveness of eplerenone compared with placebo in these patients . Methods and Results —A total of 6632 patients with left ventricular systolic dysfunction and heart failure after acute myocardial infa rct ion were r and omized to eplerenone or placebo and followed up for a mean of 16 months . The co primary end points were all-cause mortality and the composite of cardiovascular mortality/cardiovascular hospitalization . The evaluation of re source use included hospitalizations , outpatient services , and medications . Eplerenone was priced at the average wholesale price , $ 3.60 per day . Survival beyond the trial period was estimated from data from the Framingham Heart Study , the Saskatchewan Health data base , and the Worcester Heart Attack Registry . The incremental cost-effectiveness of eplerenone in cost per life-year and quality -adjusted life-year gained compared with placebo was estimated . The number of life-years gained with eplerenone was 0.1014 based on Framingham ( 95 % CI , 0.0306 to 0.1740 ) , 0.0636 with Saskatchewan ( 95 % CI , 0.0229 to 0.1038 ) , and 0.1337 with Worcester ( 95 % CI , 0.0438 to 0.2252 ) data . Cost was $ 1391 higher over the trial period in the eplerenone arm ( 95 % CI , 656 to 2165 ) because of drug cost . The incremental cost-effectiveness ratio was $ 13 718 per life-year gained with Framingham ( 96.7 % under $ 50 000 per life-year gained ) , $ 21 876 with Saskatchewan , and $ 10 402 with Worcester . Conclusions —Eplerenone compared with placebo in the treatment of heart failure after acute myocardial infa rct ion is effective in reducing mortality and is cost-effective in increasing years of life by commonly used criteria The TOwards a Revolution in COPD Health ( TORCH ) study was a 3-yr multicentre trial of 6,112 patients r and omised to salmeterol ( Salm ) , fluticasone propionate ( FP ) , a Salm/FP combination ( SFC ) or placebo ( P ) . Here the cost-effectiveness of treatments evaluated in the TORCH study is assessed . For four regions , 3-yr all-cause hospitalisation , medication and outpatient care costs were calculated . The sample was restricted to the 21 countries ( n = 4,237 ) in which European quality of life five-dimension ( EQ-5D ) data were collected in order to estimate the number of quality -adjusted life years ( QALYs ) . Regression models were fitted to survival , study medication cost , other medication cost and EQ-5D data in order to estimate total cost , number of QALYs and cost per QALY , adjusted for missing data and region . SFC had a trial-wide estimate of cost per QALY of 43,600 US dollars ( USD ) compared with P ( 95 % confidence interval 21,400–123,500 USD ) . Estimates for Salm versus P ( 197,000 USD ) and FP versus P ( 78,000 USD ) were less favourable . The US estimates were greater than those from other regions ; for SFC versus P , the cost per QALY was 77,100 ( 46,200–241,700 ) USD compared to 24,200 ( 15,200–56,100 ) USD in Western Europe . Compared with P , SFC has a lower incremental cost-effectiveness ratio than either FP or Salm used alone , and is , therefore , preferred to these monotherapies on the grounds of cost-effectiveness BACKGROUND Allergic rhinoconjunctivitis is a global health problem . Around 14 million people in Spain , France , Italy , and Austria suffer from grass pollen induced allergic rhinitis . St and ard care only provides symptoms relief , while allergen specific immunotherapy ( SIT ) treats the underlying cause of the disease . Grazax from ALK-Abelló is a new , tablet-based , effective route of SIT for home treatment . The objective was to assess the cost-effectiveness of Grazax in four Southern European countries . METHODS A prospect i ve pharmacoeconomic analyses was carried out alongside a multinational , clinical trial measuring the efficacy of Grazax . Pooled data on re source use and health outcomes were collected . A societal perspective was adopted , and the analysis had a nine-year time horizon . The primary outcome measure was quality adjusted life years ( QALYs ) . RESULTS Grazax was superior to st and ard care for all efficacy endpoints , including QALYs gained , and result ed in significantly less use of rescue medication and fewer hours missed from work . Grazax was cost-effective for all countries for an annual price in the range of 1500 euros - 1900 euros . The result was improved by inclusion of future costs of asthma and exclusion of Spanish trial centers which experienced an exceptionally low pollen season . CONCLUSION The analysis illustrates that allergen SIT with Grazax for grass pollen induced rhinoconjunctivitis is a cost-effective intervention in Southern Europe OBJECTIVES We sought to evaluate the long-term cost-effectiveness of clopidogrel for up to one year after an acute coronary syndrome ( ACS ) without ST-segment elevation . BACKGROUND The efficacy of platelet inhibition with clopidogrel for up to one year after ACS was demonstrated in the Clopidogrel in Unstable angina to prevent Recurrent Events ( CURE ) trial , a r and omized trial of 12,562 patients in 28 countries that was conducted between 1998 and 2000 . Patients were given clopidogrel ( 300-mg load followed by 75 mg/day ) versus placebo , both in addition to aspirin , for a mean of nine months . METHODS We used patient-level clinical outcomes and re source use from the CURE trial and estimates of life expectancy gains as a result of the prevention of the clinical events of death , stroke , and myocardial infa rct ion on the basis of data from external sources . RESULTS Excluding clopidogrel costs , average costs of hospitalizations alone were 325 dollars less for the clopidogrel arm ( 95 % confidence interval -722 dollars to 45 dollars ) using diagnosis-related group-based Medicare reimbursement rates . When including clopidogrel costs ( 766 dollars greater for the clopidogrel arm ) , average total costs were 442 dollars higher for the clopidogrel arm ( 95 % confidence interval 62 dollars to 820 dollars ) . The incremental cost-effectiveness ratio ( ICER ) on the basis of the Framingham Heart Study was 6,318 dollars per life-year gained ( LYG ) with clopidogrel , with 94 % of bootstrap-derived ICER estimates < 50,000 dollars/LYG ; based on Saskatchewan , the ICER was 6,475 dollars/LYG with 98 % of estimates < 50,000 dollars . CONCLUSIONS Platelet inhibition with clopidogrel in patients for up to one year after presentation with an acute coronary syndrome is both effective and cost-effective Abstract : Background : Everolimus decreases acute rejection and cardiac allograft vasculopathy after heart transplantation . We compared within‐trial costs and re source use over 1 yr of follow‐up in de novo heart transplant patients r and omized to everolimus 1.5 mg/d ( n = 209 ) , everolimus 3.0 mg/d ( n = 211 ) , or azathioprine ( n = 214 ) OBJECTIVES We used a U.S. model of health care costs to examine the cost effectiveness of enoxaparin compared with unfractionated heparin ( UFH ) as adjunctive therapy for fibrinolysis in patients with ST-segment elevation myocardial infa rct ion ( STEMI ) . BACKGROUND The ExTRACT-TIMI 25 ( Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infa rct ion Treatment-Thrombolysis In Myocardial Infa rct ion 25 ) study , a large , r and omized , multinational trial , demonstrated a reduction in death or nonfatal myocardial infa rct ion when enoxaparin was used instead of UFH as adjunctive therapy for fibrinolysis in patients with STEMI . METHODS We used patient-level clinical outcomes and re source use from the ExTRACT-TIMI 25 trial and estimates of life expectancy gains as a result of the prevention of the clinical events on the basis of the Framingham Heart Study . RESULTS Index hospitalization costs trended lower by $ 126 in the enoxaparin group ( 95 % confidence interval [ CI ] : -$295 to $ 49 ) . Thirty-day costs trended higher by $ 102 for enoxaparin ( 95 % CI : $ 108 to $ 314 ) . Patients receiving enoxaparin gained an average of 0.12 life-years relative to patients given UFH . Estimated total lifetime costs were $ 1,207 higher in the enox Output:	Conclusion Based on this systematic review , we concluded that the uptake of more advanced statistical methods has been relatively slow , while simpler naïve methods are still routinely employed
MS21865	*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: 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 Diabetes is becoming one of the most common chronic diseases , and ulcers are its most serious complication . Beginning with neuropathy , the subsequent foot wounds frequently lead to lower extremity amputation , even in the absence of critical limb ischemia . In recent years , some research ers have studied external shock wave therapy ( ESWT ) as a new approach to soft tissue wound healing . The rationale of this study was to evaluate if ESWT is effective in the management of neuropathic diabetic foot ulcers . Methods We design ed a r and omized , prospect i ve , controlled study in which we recruited 30 patients affected by neuropathic diabetic foot ulcers and then divided them into two groups based on different management strategies . One group was treated with st and ard care and shock wave therapy . The other group was treated with only st and ard care . The healing of the ulcers was evaluated over 20 weeks by the rate of re-epithelization . Results After 20 weeks of treatment , 53.33 % of the ESWT-treated patients had complete wound closure compared with 33.33 % of the control patients , and the healing times were 60.8 and 82.2 days , respectively ( p < 0.001 ) . Significant differences in the index of the re-epithelization were observed between the two groups , with values of 2.97 mm2/die in the ESWT-group and 1.30 mm2/die in the control group ( p < 0.001 ) . Conclusion Therefore , ESWT may be a useful adjunct in the management of diabetic foot ulceration . Trial registration Current Controlled Trials IS RCT OBJECTIVE This study was conducted to evaluate the efficacy of extracorporeal shock wave therapy ( ESWT ) on the healing rate , wound surface area and wound bed preparation in chronic diabetic foot ulcers ( DFU ) . METHODS Thirty eight patients with 45 chronic DFU were r and omly assigned into ; the ESWT-group ( 19 patients /24 ulcers ) and the control-group ( 19 patients /21 ulcers ) . Blinded therapist measured wound surface area ( WSA ) , the percentage of reduction in the WSA , rate of healing and wound bed preparation at baseline , after the end of the interventions ( W8 ) , and at 20-week follow-up ( W20 ) . The ESWT group received shock wave therapy twice per week for a total of eight treatments . Each ulcer was received ESWT at a frequency of 100 pulse/cm(2 ) , and energy flux density of 0.11mJ/cm(2 ) . All patients received st and ardized wound care consisting of debridement , blood-glucose control agents , and footwear modification for pressure reduction . RESULTS The overall clinical results showed completely healed ulcers in 33.3 % and 54 % in ESWT-groups and 14.28 % and 28.5 % in the control group after intervention ( W8 ) , and at follow-up ( W20 ) respectively . The average healing time was significantly lower ( 64.5 ± 8.06 days vs 81.17 ± 4.35 days , p<0.05 ) in the ESWT-group compared with the control group . CONCLUSION ESWT-treated ulcers had a significant reduction in wound size and median time required for ulcer healing , with no adverse reactions . So , the ESWT is advocated as an adjunctive therapy in chronic diabetic wound BACKGROUND This prospect i ve study compared extracorporeal shockwave treatment ( ESWT ) with hyperbaric oxygen therapy ( HBO ) in chronic diabetic foot ulcers . PATIENTS AND METHODS Seventy-two patients with 72 chronic diabetic foot ulcers were r and omly divided into two groups of similar demographics with 34 patients with 36 ulcers in the ESWT group and 36 patients with 36 ulcers in the HBO group . Patients in the ESWT group received 300 + 100/cm(2 ) impulses of shockwave at 0.11 mJ/cm(2 ) energy flux density every 2 wk for 6 wk , whereas patients in the HBO group received HBO daily for 20 treatments . The evaluations included clinical assessment of the ulcers with photo-documentation , blood flow perfusion scan , bacteriological examination , histological study , and immunohistochemical analysis . RESULTS The overall results showed completely healed in 31 % , improved in 58 % , and unchanged in 11 % for the ESWT group and 22 % completely healed , 50 % improved , and 28 % unchanged for the HBO group . The ESWT group showed significantly better clinical results and local blood flow perfusion , higher cell concentration , and activity than the HBO group . On immunohistochemical analysis , the ESWT group demonstrated significant increases in endothelial nitric oxide synthase , vessel endothelial growth factor , and proliferation cell nuclear antigen expressions and a decrease in transference-mediated digoxigenin-deoxy-UTP nick end-labeling expression than the HBO group . CONCLUSIONS ESWT appears to be more effective than HBO in chronic diabetic foot ulcers BACKGROUND Intermittent claudication is the most common symptom of peripheral arterial disease . Previous research has suggested that extracorporeal shockwave therapy ( ESWT ) may induce angiogenesis in treated tissue . The objective of this feasibility pilot trial was to assess the safety , tolerability , and efficacy of ESWT as a novel treatment . METHODS Patients with unilateral claudication were r and omized to receive ESWT or sham treatment to the calf muscle three times per week for 3 weeks . Primary outcomes were pain-free walking distance ( PFWD ) and maximum walking distance ( MWD ) . Secondary outcomes included safety and tolerability of ESWT treatment , ankle-brachial index before and after exercise , and quality of life assessed using generic ( 36-Item Short Form Health Survey , EuroQol-5 Dimension 3-Level ) and disease-specific ( Vascular Quality of Life ) instruments . Participants were assessed at baseline and 4 , 8 , and 12 weeks after treatment . Feasibility outcomes included recruitment and attendance rates for treatment and follow-up . RESULTS Thirty patients were recruited in total . Statistically significant ( P < .05 ) improvements at all time points were observed in the active treatment group for both MWD and PFWD compared with the sham treatment group . PFWD improved by 276 % in the active group and MWD improved by 167 % in the active group at 12 weeks after treatment . There were no immediate or delayed treatment safety concerns or documented adverse effects of treatment with ESWT in this trial . CONCLUSIONS ESWT is safe and well tolerated when it is applied to the calf and demonstrated significant improvements in walking distances . Current conservative management of intermittent claudication includes supervised exercise . The early results with ESWT as an alternative , noninvasive treatment option show great potential . The mechanism of action , durability of the clinical effect , and cost-effectiveness of ESWT for claudication require further investigation Objective : The Society for Vascular Surgery Wound , Ischemia , and foot Infection ( WIfI ) threatened limb classification has been shown to correlate well with risk of major amputation and time to wound healing in heterogeneous diabetic and nondiabetic population s. Major amputation continues to plague the most severe stage 4 WIfI patients , with 1‐year amputation rates of 20 % to 64 % . Our aim was to determine the association between WIfI stage and wound healing and major amputation among patients with diabetic foot ulcers ( DFUs ) treated in a multidisciplinary setting . Methods : All patients presenting to our multidisciplinary DFU clinic from July 2012 to December 2015 were enrolled in a prospect i ve data base . Wound healing and major amputation were compared for patients stratified by WIfI classification . Results : There were 217 DFU patients with 439 wounds ( mean age , 58.3 ± 0.8 years ; 58 % male , 63 % black ) enrolled , including 28 % WIfI stage 1 , 11 % stage 2 , 33 % stage 3 , and 28 % stage 4 . Peripheral arterial disease and dialysis were more common in patients with advanced ( stage 3 or 4 ) wounds ( P ≤ .05 ) . Demographics of the patients , socioeconomic status , and comorbidities were otherwise similar between groups . There was a significant increase in the number of active wounds per limb at presentation with increasing WIfI stage ( stage 1 , 1.1 ± 0.1 ; stage 4 , 1.4 ± 0.1 ; P = .03 ) . Mean wound area ( stage 1 , 2.6 ± 0.6 cm2 ; stage 4 , 15.3 ± 2.8 cm2 ) and depth ( stage 1 , 0.2 ± 0.0 cm ; stage 4 , 0.8 ± 0.1 cm ) also increased progressively with increasing wound stage ( P < .001 ) . Minor amputations ( stage 1 , 18 % ; stage 4 , 56 % ) and revascularizations ( stage 1 , 6 % ; stage 4 , 55 % ) were more common with increasing WIfI stage ( P < .001 ) . On Kaplan‐Meier analysis , WIfI classification was predictive of wound healing ( P < .001 ) but not of major amputation ( P = .99 ) . For stage 4 wounds , the mean wound healing time was 190 ± 17 days , and risk of major amputation at 1 year was 5.7 % ± 3.2 % . Conclusions : Among patients with DFU , the WIfI classification system correlated well with wound healing but was not associated with risk of major amputation at 1 year . Although further prospect i ve research is warranted , our results suggest that use of a multidisciplinary approach for DFUs may augment healing time and reduce amputation risk compared with previously published historical controls of st and ard wound care among patients with advanced stage 4 disease OBJECTIVE To investigate the efficacy of extracorporeal shockwave therapy ( ESWT ) on healing chronic diabetic foot ulcers ( DFU ) . METHOD Patients with chronic DFUs were r and omised ( 1:1 ) to receive a series of six ESWT treatments over 3 weeks in combination with st and ard care or st and ard care alone . ESWT was performed on DFUs using 250 shocks/cm2 and 500 shocks on arterial beds supplying the ulcer location . RESULTS We recruited 23 patients , 11 in the intervention group and 12 in the control . Transcutaneous oxygen tension was significantly increased in patients treated with ESWT compared with those receiving st and ard care alone at 3 weeks ( p=0.044 ) . Ulcer area reduction was 34.5 % in the intervention group versus 5.6 % in the control group at 7 weeks ( p=0.387 ) . Within-group analysis revealed a significant reduction of ulcer area in the intervention group ( p<0.01 ) , while healing was not demonstrated in the control group ( p>0.05 ) ( data tested for trend ) . CONCLUSION This r and omised study indicates a potential beneficial effect of ESWT on ulcer healing as well as tissue oxygenation . Owing to weaknesses of the study and the fact that ulcer healing was not significantly improved in the intervention group compared with the control group , a larger r and omised trial with blinded design is suggested AIM To identify any significant differences in physiological test results between healing and non healing amputation sites . METHODS A single center prospect i ve non-experimental study design was conducted on fifty subjects living with type 2 diabetes and requiring a forefoot or toe amputation . Subjects underwent non-invasive physiological testing preoperatively . These included assessment of pedal pulses , preoperative arterial spectral waveforms at the ankle , absolute toe pressures , toe-brachial pressure index and ankle-brachial pressure index . After 6 weeks , patients were examined to assess whether the amputation site was completely healed , was healing , had developed complications , or did not heal . RESULTS There was no significant difference in ABPI between the healed/healing and the non-healing groups . Mean TBI ( p=0.031 ) and toe pressure readings ( p=0.014 ) were significantly higher in the healed/healing group compared to the non healing group . A significant difference was also found in ankle spectral waveforms between the two groups ( p=0.028 ) . CONCLUSIONS TBIs , toe pressures and spectral waveforms at the ankle are better predictors of likelihood of healing and non-healing after minor amputation than ABPIs . ABPI alone is a poor indicator of the likelihood of healing of minor amputations and should not be relied on to determine need for revascularization procedures before minor amputation Output:	There was variable evidence of effect on the blood flow perfusion rate . This systematic review concludes that ESWT has the potential to improve healing in DFUs , although there is , as yet , insufficient evidence to justify its use in routine clinical practice .
MS21866	*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 the safety and efficacy of intravenous ( IV ) sodium ferric gluconate complex ( FG ) , oral ferrous sulfate , or no iron to increase hemoglobin ( Hb ) in anemic cancer patients receiving chemotherapy and epoetin alfa . PATIENTS AND METHODS In this open-label , multicenter trial , 187 patients with chemotherapy-related anemia ( Hb < 11 g/dl ; serum ferritin > or = 100 ng/ml or transferrin saturation > or = 15 % ) scheduled to receive chemotherapy and epoetin alfa ( 40,000 U subcutaneously weekly ) were r and omized to 8 weeks of 125 mg of IV FG weekly , 325 mg of oral ferrous sulfate three times daily , or no iron . The primary outcome was a change in Hb from baseline to endpoint , first whole-blood or red blood cell transfusion , or study withdrawal . RESULTS One hundred twenty-nine patients were evaluable for efficacy ( FG , n = 41 ; oral iron , n = 44 ; no iron , n = 44 ) . Mean increase in Hb was 2.4 g/dl ( 95 % confidence interval [ CI ] , 2.1 - 2.7 ) for FG ( p = .0092 vs. oral iron ; p = .0044 vs. no iron ) , 1.6 g/dl ( 95 % CI , 1.1 - 2.1 ) for oral iron ( p = .7695 vs. no iron ) , and 1.5 g/dl ( 95 % CI , 1.1 - 1.9 ) for no iron . Hb response ( increase > or = 2 g/dl ) was 73 % for FG ( p = .0099 vs. oral iron ; p = .0029 vs. no iron ) , 46 % for oral iron ( p = .6687 vs. no iron ) , and 41 % for no iron . FG was well tolerated . CONCLUSION For cancer patients with chemotherapy-related anemia receiving epoetin alfa , FG produces a significantly greater increase in Hb and Hb response compared with oral iron or no iron , supporting more aggressive treatment with IV iron supplementation for these patients Aims Therapy with i.v . iron in patients with chronic heart failure ( CHF ) and iron deficiency ( ID ) improves symptoms , functional capacity , and quality of life . We sought to investigate whether these beneficial outcomes are independent of anaemia . Methods and results FAIR-HF r and omized 459 patients with CHF [ NYHA class II or III , LVEF ≤40 % ( NYHA II ) or ≤45 % ( NYHA III ) ] and ID to i.v . iron as ferric carboxymaltose ( FCM ) or placebo in a 2:1 ratio . We analysed the efficacy and safety according to the presence or absence of anaemia ( haemoglobin ≤120 g/L ) at baseline . Of 459 patients , 232 had anaemia at baseline ( 51 % ) . The effect of FCM on the primary endpoints of self-reported Patient Global Assessment ( PGA ) and NYHA class at week 24 was similar in patients with and without anaemia [ odds ratio ( OR ) for improvement , 2.48 vs. 2.60 , P = 0.97 for PGA and 1.90 vs. 3.39 , P = 0.51 for NYHA ) . Results were also similar for the secondary endpoints , including PGA and NYHA at weeks 4 and 12 , 6 min walk test distance , Kansas City Cardiomyopathy Question naire overall score , and European Quality of Life-5 Dimensions Visual Analogue Scale at most time points . Regarding safety , no differences were noticed in the rates of death or first hospitalization between FCM and placebo both in anaemic and in non-anaemic patients . Conclusions Treatment of ID with FCM in patients with CHF is equally efficacious and shows a similar favourable safety profile irrespective of anaemia . Iron status should be assessed in symptomatic CHF patients both with and without anaemia and treatment of ID should be considered BACKGROUND Iron deficiency may impair aerobic performance . This study aim ed to determine whether treatment with intravenous iron ( ferric carboxymaltose ) would improve symptoms in patients who had heart failure , reduced left ventricular ejection fraction , and iron deficiency , either with or without anemia . METHODS We enrolled 459 patients with chronic heart failure of New York Heart Association ( NYHA ) functional class II or III , a left ventricular ejection fraction of 40 % or less ( for patients with NYHA class II ) or 45 % or less ( for NYHA class III ) , iron deficiency ( ferritin level < 100 microg per liter or between 100 and 299 microg per liter , if the transferrin saturation was < 20 % ) , and a hemoglobin level of 95 to 135 g per liter . Patients were r and omly assigned , in a 2:1 ratio , to receive 200 mg of intravenous iron ( ferric carboxymaltose ) or saline ( placebo ) . The primary end points were the self-reported Patient Global Assessment and NYHA functional class , both at week 24 . Secondary end points included the distance walked in 6 minutes and the health-related quality of life . RESULTS Among the patients receiving ferric carboxymaltose , 50 % reported being much or moderately improved , as compared with 28 % of patients receiving placebo , according to the Patient Global Assessment ( odds ratio for improvement , 2.51 ; 95 % confidence interval [ CI ] , 1.75 to 3.61 ) . Among the patients assigned to ferric carboxymaltose , 47 % had an NYHA functional class I or II at week 24 , as compared with 30 % of patients assigned to placebo ( odds ratio for improvement by one class , 2.40 ; 95 % CI , 1.55 to 3.71 ) . Results were similar in patients with anemia and those without anemia . Significant improvements were seen with ferric carboxymaltose in the distance on the 6-minute walk test and quality -of-life assessment s. The rates of death , adverse events , and serious adverse events were similar in the two study groups . CONCLUSIONS Treatment with intravenous ferric carboxymaltose in patients with chronic heart failure and iron deficiency , with or without anemia , improves symptoms , functional capacity , and quality of life ; the side-effect profile is acceptable . ( Clinical Trials.gov number , NCT00520780 ) OBJECTIVES Anaemia is a frequent complication after cardiopulmonary bypass surgery . Iron therapy has been variably employed by medical centres over the years . In our study we test the clinical effectiveness of intravenous and oral iron supplementation in correcting anaemia , and its impact on blood transfusion requirements , in patients undergoing cardiopulmonary bypass surgery . METHODS A double-blind , r and omized , placebo-controlled clinical trial with three parallel groups of patients . Group I ( n = 54 ) : intravenous iron(III)-hydroxide sucrose complex , three doses of 100 mg/24 h during pre- and postoperative hospitalization and 1 pill/24 h of oral placebo in the same period and during 1 month after discharge . Group II ( n = 53 ) : oral ferrous fumarate iron 1 pill/24 h pre- and postoperatively and during 1 month after discharge , and intravenous placebo while hospitalized . Group III ( n = 52 ) : oral and intravenous placebo pre- and postoperatively , following the same protocol . Data were collected preoperatively , at theatre , at intensive care unit admission , before hospital discharge and 1 month later . RESULTS ( 1 ) Baseline clinical and demographic characteristics and surgical procedures were similar in the three groups ; ( 2 ) no inter-group differences were found in haemoglobin and haematocrit during the postoperative period ; ( 3 ) the intravenous iron group showed higher serum ferritin levels at hospital discharge ( 1321 ± 495 ng/ml ; P < 0.001 ) and 1 month later ( 610 ± 387 ; P < 0.001 ) compared with the other groups and ( 4 ) we did not observe statistical differences in blood transfusion requirements between the three groups . CONCLUSIONS The use of intravenous or oral iron supplementation proved ineffective in correcting anaemia after cardiopulmonary bypass and did not reduce blood transfusion requirements . [ Current Controlled Trials number : NCT01078818 ( oral and intravenous iron in patients postoperative cardiovascular surgery under EC ) ] To determine if high doses of oral iron could shorten the duration of therapy necessary to treat Fe deficiency anemia , high-dose Fe 600 mg three times per day ( given as nontoxic carbonyl Fe ) was compared with st and ard ferrous sulfate 60 mg Fe++ three times per day in a r and omized , double-blind , 3-wk trial involving 36 female blood donors with mild Fe deficiency anemia . In animal studies , both forms of Fe have similar bioavailability when administered in equal amounts . High-dose carbonyl Fe was well tolerated with gastrointestinal side effects similar those observed with st and ard FeSO4 therapy . The 10-fold larger amount of Fe result ed in a mean 1.5-fold increase in estimated Fe absorption . Both regimens corrected anemia but neither replenished storage Fe . These results suggest that the principal advantage to the use of carbonyl Fe would derive from its safety rather than from the large doses that can be given OBJECTIVE Sub clinical hypothyroidism is a health state that is associated with hypercholesterolemia , infertility , iron-deficiency anemia , and poor obstetric outcome . This article summarizes the results of a prospect i ve clinical investigation of whether treatment of sub clinical hypothyroidism and iron-deficiency anemia with a combination of levothyroxine plus iron salt would be superior to each treatment alone . METHODS In a r and omized , double-blind , active-controlled trial , 60 patients with sub clinical hypothyroidism and iron-deficiency anemia received iron salt+placebo ( 20 patients ) , levothyroxine+placebo ( 20 patients ) , or levothyroxine+iron salt ( 20 patients ) for 3 months . Change from baseline ( before ) to end of study ( after ) in hemoglobin , ferritin , and thyroid-stimulating hormone levels were compared among groups . RESULTS The increase from baseline in hemoglobin and ferritin in the levothyroxine+iron group was superior to the other groups , in which a decrease in thyroid-stimulating hormone in the 2 groups that received levothyroxine was superior to the group treated with iron salt . CONCLUSION Sub clinical hypothyroidism was investigated in iron-deficient patients with no acceptable response to iron salt alone . A combination of levothyroxine and iron salt is better than each one alone Background : The aim of this study was to compare the efficacy , safety and achievement of the target hemoglobin level ( Hb ≥10 g/dl ) in patients with preoperative anemia due to menorrhagia who received intravenous iron sucrose compared with oral iron protein succinylate for anemia management . Methods : Seventy-six patients with Hb levels < 9.0 g/dl who were scheduled to undergo surgical treatment were r and omized to receive either intravenous iron sucrose ( based on the calculated total iron deficit divided into 2 ampoule infusions intravenously 3 times a week , beginning 3 weeks before surgery ) or oral iron ( 80 mg/day of oral iron protein succinylate daily ) . Results : The intravenous iron group had higher increases in Hb ( 3.0 vs. 0.8 g/dl ; p < 0.0001 ) and ferritin levels ( 170.1 vs. 4.1 μg/l ; p < 0.0001 ) than the oral iron group . Achieving the target Hb was also higher in the intravenous iron group than in the oral iron group ( 76.7 vs. 11.5 % ; p < 0.0001 ) . There were tolerable adverse events in both groups . Conclusion : Preoperative intravenous iron sucrose administration is more effective than oral iron and is as safe as oral iron therapy in the correction of preoperative anemia due to menorrhagia 8612 Background : Patients ( pts ) with cancer receiving chemotherapy often have chemotherapy-induced anemia ( CIA ) and reduced quality of life . Darbepoetin alfa ( DA ) is an erythropoiesis-stimulating agent ( ESA ) that can effectively treat CIA when administered once every 3 weeks ( Q3W ) . In patients with CIA , limited data in the literature suggest that administration of intravenous ( IV ) iron with ESA therapy may increase clinical response . METHODS This r and omized , multicenter , open-label , 16-week study evaluated the safety and efficacy of DA 500 mcg administered Q3W using the SureClick injection device in pts with CIA ( Hb < 11 g/dL ) who received either IV iron or st and ard practice for iron administration ( oral iron or no iron ) . The dose of IV iron was 200 mcg administered either Q3W with DA Q3W or , if required , as 2 doses ( 200 mcg total ) within a 3-week period . Pts who received ≥ 1 do Output:	Adverse effects related to oral iron treatment included nausea , diarrhoea and constipation ; most were mild . Thus , little evidence was found to support the use of one preparation or regimen over another . Subgroup analyses did not reveal consistent results ; therefore we were unable to determine whether iron is useful in specific clinical situations , or whether iron therapy might be useful for people who are receiving erythropoietin . • Very low- quality evidence suggests that oral iron might decrease the proportion of people who require blood transfusion , and no evidence indicates that it decreases mortality .
MS21867	*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 cerebellum is known to play a strong functional role in both motor control and motor learning . Hence , the benefit of physiotherapeutic training remains controversial for patients with cerebellar degeneration . In this study , we examined the effectiveness of a 4-week intensive coordinative training for 16 patients with progressive ataxia due to cerebellar degeneration ( n = 10 ) or degeneration of afferent pathways ( n = 6 ) . Methods : Effects were assessed by clinical ataxia rating scales , individual goal attainment scores , and quantitative movement analysis . Four assessment s were performed : 8 weeks before , immediately before , directly after , and 8 weeks after training . To control for variability in disease progression , we used an intraindividual control design , where performance changes with and without training were compared . Results : Significant improvements in motor performance and reduction of ataxia symptoms were observed in clinical scores after training and were sustained at follow-up assessment . Patients with predominant cerebellar ataxia revealed more distinct improvement than patients with afferent ataxia in several aspects of gait like velocity , lateral sway , and intralimb coordination . Consistently , in patients with cerebellar but without afferent ataxia , the regulation of balance in static and dynamic balance tasks improved significantly . Conclusion : In patients with cerebellar ataxia , coordinative training improves motor performance and reduces ataxia symptoms , enabling them to achieve personally meaningful goals in everyday life . Training effects were more distinct for patients whose afferent pathways were not affected . For both groups , continuous training seems crucial for stabilizing improvements and should become st and ard of care . Level of evidence : This study provides Class III evidence that coordinative training improves motor performance and reduces ataxia symptoms in patients with progressive cerebellar ataxia Occupational therapy ( OT ) is a profession concerned with promoting health and well-being through occupation , by enabling h and icapped people to participate in the activities of everyday life . OT is part of the clinical rehabilitation of progressive genetic neurodegenerative diseases such as spinocerebellar ataxias ; however , its effects have never been determined in these diseases . Our aim was to investigate the effect of OT on both physical disabilities and depressive symptoms of spinocerebellar ataxia type 3 ( SCA3 ) patients . Genomically diagnosed SCA3 patients older than 18 years were invited to participate in the study . Disability , as evaluated by functional independence measurement and Barthel incapacitation score , Hamilton Rating Scale for Depression , and World Health Organization Quality of Life question naire ( WHOQOL-BREF ) , was determined at baseline and after 3 and 6 months of treatment . Twenty-six patients agreed to participate in the study . All were treated because OT prevents blinding of a control group . Fifteen sessions of rehabilitative OT were applied over a period of 6 months . Difficult access to food , clothing , personal hygiene , and leisure were some of the main disabilities focused by these patients . After this treatment , disability scores and quality of life were stable , and the Hamilton scores for depression improved . Since no medication was started up to 6 months before or during OT , this improvement was related to our intervention . No association was found between these endpoints and a CAG tract of the MJD1 gene ( CAGn ) , age , age of onset , or neurological scores at baseline ( Spearman test ) . Although the possibly temporary stabilization of the downhill disabilities as an effect of OT remains to be established , its clear effect on depressive symptoms confirms the recommendation of OT to any patient with SCA3 or spinocerebellar ataxia Locomotor adaptability ranges from the simple and fast-acting to the complex and long-lasting and is a requirement for successful mobility in an unpredictable environment . Several neural structures , including the spinal cord , brainstem , cerebellum , and motor cortex , have been implicated in the control of various types of locomotor adaptation . However , it is not known which structures control which types of adaptation and the specific mechanisms by which the appropriate adjustments are made . Here , we used a splitbelt treadmill to test cerebellar contributions to two different forms of locomotor adaptation in humans . We found that cerebellar damage does not impair the ability to make reactive feedback-driven motor adaptations , but significantly disrupts predictive feedforward motor adaptations during splitbelt treadmill locomotion . Our results speak to two important aspects of locomotor control . First , we have demonstrated that different levels of locomotor adaptability are clearly dissociable . Second , the cerebellum seems to play an essential role in predictive but not reactive locomotor adjustments . We postulate that reactive adjustments may instead be predominantly controlled by lower neural centers , such as the spinal cord or brainstem Objective : To investigate the feasibility of a r and omized controlled trial of a home-based balance intervention for people with cerebellar ataxia . Design : A r and omized controlled trial design . Setting : Intervention and assessment took place in the home environment . Participants : A total of 12 people with spinocerebellar ataxia type 6 were r and omized into a therapy or control group . Both groups received identical assessment s at baseline , four and eight weeks . Interventions : Therapy group participants undertook balance exercises in front of optokinetic stimuli during weeks 4–8 , while control group participants received no intervention . Main measures : Test – retest reliability was analysed from outcome measures collected twice at baseline and four weeks later . Feasibility issues were evaluated using daily diaries and end trial exit interviews . Results : The home-based training intervention with opto-kinetic stimuli was feasible for people with pure ataxia , with one drop-out . Test – retest reliability is strong ( intraclass correlation coefficient > 0.7 ) for selected outcome measures evaluating balance at impairment and activity levels . Some measures reveal trends towards improvement for those in the therapy group . Sample size estimations indicate that Bal-SARA scores could detect a clinical ly significant change of 0.8 points in this functional balance score if 80 people per group were analysed in future trials . Conclusions : Home-based targeted training of functional balance for people with pure cerebellar ataxia is feasible and the outcome measures employed are reliable Balance and gait problems in patients with cerebellar degeneration lead to reduced mobility , loss of independence , and frequent falls . It is currently unclear , however , whether balance and gait capacities can be improved by training in this group of patients . Therefore , the aim of this study was to examine the effects of gait adaptability training on obstacle avoidance and dynamic stability during adaptive gait . Ten patients with degenerative cerebellar ataxia received 10 protocol ized gait adaptability training sessions of 1 h each during 5 weeks . Training was performed on a treadmill with visual stepping targets and obstacles projected on the belt 's surface . As the primary outcome , we used an obstacle avoidance task while walking on a treadmill . We determined avoidance success rates , as well as dynamic stability during the avoidance manoeuvre . Clinical ratings included the scale for the assessment of ataxia ( SARA ) , 10 m walking test , timed up- and -go test , berg balance scale , and the obstacle subtask of the emory functional ambulation profile ( EFAP ) . Following the intervention , success rates on the obstacle avoidance task had significantly improved compared to pre-intervention . For successful avoidance , participants allowed themselves smaller stability margins in the sagittal plane in the ( shortened ) pre-crossing step . However , in the subsequent steps they returned to baseline stability values more effectively than before training . SARA scores and the EFAP obstacle subtask improved significantly as well . This pilot study provides preliminary evidence of a beneficial effect of gait adaptability training on obstacle avoidance capacity and dynamic stability in patients with cerebellar degeneration Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists Objective . To investigate short- and long-term effects of intensive rehabilitation on ataxia , gait , and activities of daily living ( ADLs ) in patients with degenerative cerebellar disease . Methods . A total of 42 patients with pure cerebellar degeneration were r and omly assigned to the immediate group or the delayed-entry control group . The immediate group received 2 hours of inpatient physical and occupational therapy , focusing on coordination , balance , and ADLs , on weekdays and 1 hour on weekends for 4 weeks . The control group received the same intervention after a 4-week delay . Short-term outcome was compared between the immediate and control groups . Long-term evaluation was done in both groups at 4 , 12 , and 24 weeks after the intervention . Outcome measures included the assessment and rating of ataxia , Functional Independence Measure , gait speed , cadence , functional ambulation category , and number of falls . Results . The immediate group showed significantly greater functional gains in ataxia , gait speed , and ADLs than the control group . Improvement of truncal ataxia was more prominent than limb ataxia . The gains in ataxia and gait were sustained at 12 weeks and 24 weeks , respectively . At least 1 measure was better than at baseline at 24 weeks in 22 patients . Conclusions . Short-term benefit of intensive rehabilitation was evident in patients with degenerative cerebellar diseases . Although functional status tended to decline to the baseline level within 24 weeks , gains were maintained in more than half of the participants Exercise therapy ( ET ) can be beneficial in disabled multiple sclerosis ( MS ) patients . Intermittent transcranial magnetic theta burst stimulation ( iTBS ) induces long-term excitability changes of the cerebral cortex and may ameliorate spasticity in MS . We investigated whether the combination of iTBS and a program of ET can improve motor disability in MS patients . In a double-blind , sham-controlled trial , 30 participants were r and omized to three different interventions : iTBS plus ET , sham stimulation plus ET , and iTBS alone . Before and after 2 weeks of treatment , measures of spasticity through the modified Ashworth scale ( MAS ) and the 88 items Multiple Sclerosis Spasticity Score question naire ( MSSS-88 ) , fatigue through the Fatigue Severity Scale ( FSS ) , daily living activities ( ADL ) through the Barthel index and health-related quality of life ( HRQoL ) through the 54 items Multiple Sclerosis Quality of life inventory ( MSQoL-54 ) were collected . iTBS plus ET reduced MAS , MSSS-88 , FSS scores , while in the Barthel index and MSQoL-54 , physical composite scores were increased . iTBS alone caused a reduction of the MAS score , while none of the measured scales showed significant changes after sham iTBS plus ET . iTBS associated with ET is a promising tool for motor rehabilitation of MS patients Friedreich ’s ataxia results in morbidity because of many factors ; progressive equinovarus deformity is one of these . We studied the risk factors and incidence of this deformity . We sought to assess whether surgical management of fixed equinovarus deformity leads to functional improvement . Thirty-six patients with Friedrich ’s ataxia were assessed for this deformity . These patients were treated by splinting , botulinum toxin Type A injection , and surgery , as indicated by the severity , followed by an ongoing rehabilitation program . The effect of surgery was assessed using subscales of the Barthel index and functional independence measure . Severe foot deformities in which either surgery or botulinum toxin injection was recommended correlated with current age , years since disease onset , and years that the patient required a wheelchair for mobility , but not with the GAA repeat size or age at disease onset . Function and mobility were improved after surgery compared with a similar period before surgery . Three of seven patients who had surgery had significant complications . Aggressive management of foot deformities should be considered , and active measures to prevent permanent foot deformities should be pursued to maximize quality of life and independence of patients with Friedreich ’s ataxia . Level of Evidence : Therapeutic study , Level IV ( case series-no , or historical control group Few clinical studies have evaluated physiotherapeutic interventions for patients with degenerative cerebellar disease . In particular , evidence for long-term effects and transfer to activities of daily life is rare . We have recently shown that coordinative training leads to short-term improvements in motor performance . To evaluate long-term benefits and translation to real world function , we here assessed motor performance and achievements in activities of daily life 1 year after a 4 week intensive coordinative training , which was followed by a home training program . Effects were assessed by clinical rating scales , a goal attainment score and quantitative movement analysis . Despite gradual decline of motor performance and gradual increase of ataxia symptoms due to progression of disease after 1 year , improvements in motor performance and achievements in activities of daily life persisted . Thus , also in patients with degenerative cerebellar disease , continuous coordinative training leads to long-term improvements , which translate to real world function Recent research indicates that physiotherapy can improve motor performance of patients with cerebellar degeneration . Given the known contributions of the cerebellum to motor learning , it remains unclear whether such observable changes in performance are mediated by the Output:	There is consistent evidence that rehabilitation improves function , mobility , ataxia , and balance in genetic degenerative ataxia
MS21868	*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: We investigated whether a short course in communication skills for physicians would improve the quality of informed consent in a r and omized clinical adjuvant trial on breast cancer . In this prospect i ve , case-controlled intervention study , physicians and research nurses who introduced the cancer treatment trial to patients at three of the participating hospitals first attended a one-day communication skills course . The quality of informed consent was then evaluated by addressing a st and ardized question naire , QuIC , to trial patients at the three intervention hospitals and at control hospitals . Response rate was 90.0 % ( n = 288 ) . Of the patients treated by the intervention group , 73 % were very satisfied with the information received compared with 56 % of those of the control group ( p = 0.003 ) . The patients of the intervention group considered the time given for making their decision sufficient more often than those of the controls ( 98 % vs. 90 % , p=0.004 ) . The patients of the intervention group recalled more often than those of the controls that the physician had also offered other therapeutic options than the trial treatment ( 91 % vs. 97 % , p=0.032 ) . They also understood the main aim of the study better than the patients of the controls ( 89 % vs. 78 % , p=0.030 ) . In conclusion , a short communication skills course for the trial physicians and nurses improved the quality of informed consent and patient satisfaction in the trial OBJECTIVES : To study whether linguistic analysis and changes in information leaflets can improve readability and underst and ing . DESIGN : R and omised , controlled study . Two information leaflets concerned with trials of drugs for conditions/diseases which are commonly known were modified , and the original was tested against the revised version . SETTING : Denmark . PARTICIPANTS : 235 persons in the relevant age groups . MAIN MEASURES : Readability and underst and ing of contents . RESULTS : Both readability and underst and ing of contents was improved : readability with regard to both information leaflets and underst and ing with regard to one of the leaflets . CONCLUSION : The results show that both readability and underst and ing can be improved by increased attention to the linguistic features of the information AIMS International guidelines on ethics in biomedical research require that the informed consent of all enrolled participants is obtained . A written document describing the research , the informed consent ( IC ) document , must be given to all participants by the investigator . Most IC documents are long , containing much information . The aim of the present study was to determine whether the modification of the IC document by a working group or systematic improvement in its lexicosyntactic readability can improve comprehension of the written information given to patients participating in biomedical research . METHODS One hundred and fifty-nine patients were r and omized to read one of the three versions of the IC document : unchanged document , document modified using systematic improvement of lexicosyntactic readability and document modified by a working group . RESULTS Neither the improvement in the lexicosyntactic readability , nor the intervention of the working group significantly improved the score of objective comprehension for the subjects included in this study : it was 66.6 ( 95 % confidence interval 64.0 , 69.2 ) for the control group , 68.8 ( 66.2 , 71.4 ) for the group with the document improved for lexicosyntactic readability and 69.2 ( 66.0 , 72.4 ) for the group who read the document improved by the working group ( P= 0.38 ) . CONCLUSIONS We failed to show that improving IC document comprehension through a lexicosyntactic approach or by a working group leads to better comprehension Background Studies on different methods to supplement the traditional informed consent process have generated conflicting results . This study was design ed to evaluate whether participants who received group counseling prior to administration of informed consent understood the key components of the study and the consent better than those who received individual counseling , based on the hypothesis that group counseling would foster discussion among potential participants and enhance their underst and ing of the informed consent . Methods Parents of children participating in a trial of nutritional supplementation were r and omized to receive either group counseling or individual counseling prior to administration of the informed consent . To assess the participant 's comprehension , a structured question naire was administered approximately 48 - 72 hours afterwards by interviewers who were blinded to the allocation group of the respondents . Results A total of 128 parents were recruited and follow up was established with 118 ( 90.2 % ) for the study . All respondents were aware of their child 's participation in a research study and the details of sample collection . However , their underst and ing of study purpose , r and omization and withdrawal was poor . There was no difference in comprehension of key elements of the informed consent between the intervention and control arm . Conclusions The results suggest that the group counseling might not influence the overall comprehension of the informed consent process . Further research is required to devise better ways of improving participants ' underst and ing of r and omization in clinical trials . Trial Registration Clinical Trial Registry - India ( CTRI ) : To determine subjects ' perception of the purpose of informed consent , 113 subjects were recruited from a dose-controlled clinical trial of didanosine ( ddI ) . Subjects were surveyed regarding how they made decisions regarding their medical care in general , about how they obtained information about this trial in particular , and several aspects of the informed consent procedure . Subjects were then r and omly allocated to receive information about the trial by either a written only format or a written and verbal format 1 week before commencement of the trial . An eight-item instrument assessed knowledge of ddI prior to and subsequent to receiving information . Most subjects obtained information about HIV-related issues from their specialist ( 70 % ) or general ( 51 % ) medical practitioner . A large proportion of subjects ( 88 % ) reported that they believed their specialist medical practitioner always acted in their best interest . The majority of subjects ( 79 % ) believed that subjects should be allowed the choice between participating in the clinical trial and receiving the drug outside the trial mechanism . Of the subjects , 96 % believed that informed consent was necessary in clinical trials ; however , their opinions of the purpose of informed consent varied widely . Although they signed the informed consent , 44 % of the subjects stated that they did not underst and ' all ' of the information that was provided . We found that the provision of information by written mode alone , or written and verbal modes were both associated with significant increases in knowledge levels and that there was a significant interaction in the degree of change between the two methods , with the written plus verbal method showing the most improvement over time . There was an interaction between degree of improvement in knowledge of didanosine in subjects who received written information versus those who received written and verbal knowledge and time ( pre- versus post-consent ) and a significant main effect for time . All subjects were relatively well-informed about the drug and stated that specialist and general medical practitioners were their major source of knowledge for all aspects of their HIV health care Obtaining informed consent for clinical investigations represents a major legal , ethical , and moral consideration in human experimentation . Mechanisms for informing the patient vary widely , and usually no system exists to confirm the degree of information retained by the patient . A Veterans Administration Cooperative Study , begun in 1975 , has used a videotape information package in addition to a st and ard written consent form to ensure uniformity . Each presentation was followed by a question naire to assess the amount of material learned before attempting r and omization . Repeated showings were occasionally necessary and did not affect the rate of r and omization . A videotape presentation , especially in cooperative studies , ensures uniformity , makes allowance for varying educational levels of patients , and provides documentation of the degree of informed consent IN THE EARLY 1890S , DR WILLIAM HALSTED DEVELOPED radical mastectomy for breast cancer . Surgeons performed the Halsted procedure for more than 80 years even though there was little systematic evidence for its success . Then a new breed of scholars subjected the procedure to formal methods of evaluation unknown to Halsted . The methods —r and omized controlled trials ( RCTs ) principal among them — led to a surprise : radical mastectomy had no advantage over simpler forms of treatment . This is but 1 example of the hard-won victory of evidence over belief in medicine . The pioneers of the formal evaluation of medical practice s raised questions that traditional practitioners did not welcome . But in time , formal evaluation prevailed . The pioneers developed a hierarchy of evidentiary rigor relating the design of a study to the confidence that could be placed in the findings , from the lowly , nearly valueless anecdote to the royalty of evidence , the RCT . Concurrently , a similar story of hard-won learning unfolded in the so-called quality movement . Scholars illuminated the scale and types of defects in the processes of care and the outcomes , including high rates of unscientific care , inappropriate care , geographic variations in practice , latent disagreements among specialists , and oftenunrecognized medical injury to patients . Like the pioneers of evidence -based medicine , students of medical quality were at first largely ignored , but no longer . In 1999 and 2001 , the Institute of Medicine published 2 l and mark reports on the evidence for quality failures and called urgently for re design of care systems to achieve improvements . The story could end here happily with 2 great streams of endeavor merging into a framework for conjoint action : improving clinical evidence and improving the process of care . Instead , the 2 endeavors are often in unhappy tension . Neither disputes that progress toward health care ’s main goal , the relief of illness and pain , requires research of many kinds : basic , clinical , systems , epidemiologic . The disagreement centers on epistemology — ways to get at “ truth ” and how those ways should vary depending on the knowledge sought . Individuals most involved in day-to-day improvement work fear that if “ evidence ” is too narrowly defined and the approach to gathering evidence too severely constrained , progress may be the victim . For example , the RCT is a powerful , perhaps unequaled , research design to explore the efficacy of conceptually neat components of clinical practice —tests , drugs , and procedures . For other crucially important learning purpose s , however , it serves less well . Recent controversies about the evaluation of rapid response teams provide a case in point . These controversies show the importance of adjusting research methods to fit research questions . Although only 10 % to 15 % of in patients resuscitated outside intensive care units survive to hospital discharge , early warning signs are present in a large percentage of patients who ultimately experience cardiac arrest . Rapid response team systems bring expert clinicians to the bedsides of deteriorating patients before arrest occurs . In the mid 1990s , based largely on reports from Australian investigators , the Institute for Healthcare Improvement and others began introducing the concept to willing hospitals . Local experience strongly suggested that these systems often , although not always , were associated with improved outcomes , including reduced anxiety among nursing staff ; increased interdisciplinary teamwork ; decreased cardiac arrests outside of intensive care units ; and , in some cases , declines in mortality . The evidence base took a turn in June 2005 with the publication of the Medical Early Response Intervention and Therapy ( MERIT ) Study , a cluster r and omized prospect i ve trial that cl aim ed to find no beneficial effect of these teams on several primary outcomes . Controversy has continued since then regarding the scientific evidence for rapid response systems . In fact , the MERIT trial was not negative ; it was inconclusive . The study team encountered an array of serious problems in execution , common in social science . For example , although the study ’s power calculation assumed a baseline rate of 30 events per 1000 admissions , the actual rate proved to be fewer than 7 events per 1000 admissions ; thus , the study was ef fect ively underpowered by 500 % . Crosscontamination abounded ; some control hospitals implemented rapid response protocol s , and several study Recruitment to cancer clinical trials needs to be improved , as does patient knowledge and underst and ing about clinical trials , in order for patients to make an informed choice about whether or not to take part . Audiovisual patient information ( AVPI ) has been shown to improve knowledge and underst and ing in various areas of practice , but there is limited information about its effect in the cancer clinical trial setting , particularly in relation to consent rates . In this study , 173 patients were r and omised to receive either the AVPI , in addition to the st and ard trial-specific written information , or the written information alone . There was no difference in clinical trial recruitment rates between the two groups with similar study entry rates : 72.1 % in the AVPI group and 75.9 % in the st and ard information group . The estimated odds ratio for refusal ( intervention/no intervention ) was 1.19 ( 95 % CI 0.55–2.58 , P=0.661 ) . Knowledge scores increased more in the AVPI group compared to the st and ard group ( P=0.0072 ) . The change in anxiety score between the arms was also statistically significant ( P=0.011 ) with anxiety improving in the intervention arm more than in the no intervention arm . Audiovisual patient information was shown to be a useful tool in improving patient knowledge and anxiety , but further work is necessary in relation to its effect on clinical trial recruitment rates Procedures must be developed to ensure that valid informed consent is obtained from participants in HIV vaccine efficacy trials . A prototype informed consent process was evaluated among 4,892 persons at high risk for HIV infection in the HIV Network for Prevention Trials Vaccine Preparedness Study ( VPS ) , a prospect i ve cohort study of HIV seroincidence in eight U.S. metropolitan areas . Twenty percent of VPS participants were selected at r and om to undergo the prototype informed consent process at VPS month 3 . Participants ' knowledge of 10 key HIV vaccine trial concepts and willingness to participate in HIV vaccine efficacy trials were assessed and compared at baseline and semiannually thereafter for 18 months . Knowledge of HIV vaccine trial concepts was low at baseline . Participation in the prototype process was associated with substantial and sustained increases in knowledge ( relative risks for the 10 items , 1.04–2.26 ) , which were of similar magnitude across HIV risk groups , race/ethnicity , and educational levels . It is recommended that the prototype informed consent process be adopted for future HIV vaccine Output:	Conclusions Enhanced consent forms and extended discussion s were most effective in improving participant underst and ing . Interventions of all categories had no negative impact on participant satisfaction or study accrual .
MS21869	*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 Maternal , perinatal and neonatal mortality remains high in low-income countries . We evaluated community and facility-based interventions to reduce deaths in three districts of Malawi . Methods We evaluated a rural participatory women ’s group community intervention ( CI ) and a quality improvement intervention at health centres ( FI ) via a two-by-two factorial cluster r and omized controlled trial . Consenting pregnant women were followed-up to 2 months after birth using key informants . Primary outcomes were maternal , perinatal and neonatal mortality . Clusters were health centre catchment areas assigned using stratified computer-generated r and omization . Following exclusions , including non-birthing facilities , 61 clusters were analysed : control ( 17 clusters , 4912 births ) , FI ( 15 , 5335 ) , CI ( 15 , 5080 ) and FI + CI ( 14 , 5249 ) . This trial was registered as International St and ard R and omised Controlled Trial [ IS RCT N18073903 ] . Outcomes for 14 576 and 20 576 births were recorded during baseline ( June 2007–September 2008 ) and intervention ( October 2008–December 2010 ) periods . Results For control , FI , CI and FI + CI clusters neonatal mortality rates were 34.0 , 28.3 , 29.9 and 27.0 neonatal deaths per 1000 live births and perinatal mortality rates were 56.2 , 55.1 , 48.0 and 48.4 per 1000 births , during the intervention period . Adjusting for clustering and stratification , the neonatal mortality rate was 22 % lower in FI + CI than control clusters ( OR = 0.78 , 95 % CI 0.60–1.01 ) , and the perinatal mortality rate was 16 % lower in CI clusters ( OR = 0.84 , 95 % CI 0.72–0.97 ) . We did not observe any intervention effects on maternal mortality . Conclusions Despite implementation problems , a combined community and facility approach using participatory women ’s groups and quality improvement at health centres reduced newborn mortality in rural Malawi BACKGROUND Women 's groups and health education by peer counsellors can improve the health of mothers and children . We assessed their effects on mortality and breastfeeding rates in rural Malawi . METHODS We did a 2 × 2 factorial , cluster-r and omised trial in 185,888 people in Mchinji district . 48 equal-sized clusters were r and omly allocated to four groups with a computer-generated number sequence . 24 facilitators guided groups through a community action cycle to tackle maternal and child health problems . 72 trained volunteer peer counsellors made home visits at five timepoints during pregnancy and after birth to support breastfeeding and infant care . Primary outcomes for the women 's group intervention were maternal , perinatal , neonatal , and infant mortality rates ( MMR , PMR , NMR , and IMR , respectively ) ; and for the peer counselling were IMR and exclusive breastfeeding ( EBF ) rates . Analysis was by intention to treat . The trial is registered as IS RCT N06477126 . FINDINGS We monitored outcomes of 26,262 births between 2005 and 2009 . In a factorial model adjusted only for clustering and the volunteer peer counselling intervention , in women 's group areas , for years 2 and 3 , we noted non-significant decreases in NMR ( odds ratio 0.93 , 0.64 - 1.35 ) and MMR ( 0.54 , 0.28 - 1.04 ) . After adjustment for parity , socioeconomic quintile , and baseline measures , effects were larger for NMR ( 0.85 , 0.59 - 1.22 ) and MMR ( 0.48 , 0.26 - 0.91 ) . Because of the interaction between the two interventions , a stratified analysis was done . For women 's groups , in adjusted analyses , MMR fell by 74 % ( 0.26 , 0.10 - 0.70 ) , and NMR by 41 % ( 0.59 , 0.40 - 0.86 ) in areas with no peer counsellors , but there was no effect in areas with counsellors ( 1.09 , 0.40 - 2.98 , and 1.38 , 0.75 - 2.54 ) . Factorial analysis for the peer counselling intervention for years 1 - 3 showed a fall in IMR of 18 % ( 0.82 , 0.67 - 1.00 ) and an improvement in EBF rates ( 2.42 , 1.48 - 3.96 ) . The results of the stratified , adjusted analysis showed a 36 % reduction in IMR ( 0.64 , 0.48 - 0.85 ) but no effect on EBF ( 1.18 , 0.63 - 2.25 ) in areas without women 's groups , and in areas with women 's groups there was no effect on IMR ( 1.05 , 0.82 - 1.36 ) and an increase in EBF ( 5.02 , 2.67 - 9.44 ) . The cost of women 's groups was US$ 114 per year of life lost ( YLL ) averted and that of peer counsellors was $ 33 per YLL averted , using stratified data from single intervention comparisons . INTERPRETATION Community mobilisation through women 's groups and volunteer peer counsellor health education are methods to improve maternal and child health outcomes in poor rural population s in Africa . FUNDING Saving Newborn Lives , UK Department for International Development , and Wellcome Trust In this article we examine the cost-effectiveness of the Smiling Sun multichannel media campaign , which was undertaken in Bangladesh from 2001 to 2003 and involved a nationally broadcast television serial drama supported by radio , television , newspaper , and billboard advertisements and local promotion activities . The goal was to encourage the use of a package of family health services at NGO ( nongovernmental organization ) Service Delivery Program ( NSDP ) providers . This analysis relates the costs of the Smiling Sun campaign at the national and local level to measures of change in the use of health services , namely , antenatal care and childhood immunizations . Effectiveness is measured using data from cross-sectional surveys conducted in 2001 and 2003 in NSDP catchment areas in rural Bangladesh . The statistical approach , bivariate probit estimation , controls for nonr and om exposure to the program 's media messages , advertisements , and signs . Using national-level data , we find that the Smiling Sun campaign was both effective and cost-effective , inducing higher levels of service utilization for only $ 0.05 per additional antenatal care ( ANC ) user and only $ 0.30 and $ 0.36 for each additional child vaccinated for measles and DPT3 , respectively . With respect to local promotion activities , the cost per attributable behavior change was considerably higher — nearly $ 8 per new ANC user , $ 37 per new DPT3 vaccination , and $ 32 per new measles vaccination OBJECTIVE To evaluate and compare the cost-effectiveness of two strategies for neonatal care in Sylhet division , Bangladesh . METHODS In a cluster-r and omized controlled trial , two strategies for neonatal care -- known as home care and community care -- were compared with existing services . For each study arm , economic costs were estimated from a societal perspective , inclusive of programme costs , provider costs and household out-of-pocket payments on care-seeking . Neonatal mortality in each study arm was determined through household surveys . The incremental cost-effectiveness of each strategy --compared with that of the pre-existing levels of maternal and neonatal care -- was then estimated . The levels of uncertainty in our estimates were quantified through probabilistic sensitivity analysis . FINDINGS The incremental programme costs of implementing the home-care package were 2939 ( 95 % confidence interval , CI : 1833 - 7616 ) United States dollars ( US$ ) per neonatal death averted and US$ 103.49 ( 95 % CI : 64.72 - 265.93 ) per disability-adjusted life year ( DALY ) averted . The corresponding total societal costs were US$ 2971 ( 95 % CI : 1844 - 7628 ) and US$ 104.62 ( 95 % CI : 65.15 - 266.60 ) , respectively . The home-care package was cost-effective -- with 95 % certainty -- if healthy life years were valued above US$ 214 per DALY averted . In contrast , implementation of the community-care strategy led to no reduction in neonatal mortality and did not appear to be cost-effective . CONCLUSION The home-care package represents a highly cost-effective intervention strategy that should be considered for replication and scale-up in Bangladesh and similar setting s elsewhere OBJECTIVE To assess the cost-effectiveness of an ambulance service within a comprehensive hospital/community-based program aim ed at improving access and quality of reproductive health in poor-re sources setting s. METHODS Obstetrical cases referred to the hospital with the ambulance during a 3-month period were prospect ively recorded . Clinical indications were used to determine the effectiveness of the referral ; the direct costs of the service were calculated . Overall effectiveness was then measured against WHO thresholds . RESULTS Ninety-two obstetrical referrals were recorded . Eleven ( 12 % ) were considered effective , corresponding to 611.7 years saved . Cost per year saved was 15.82 US dollars which about half of WHO 's 30 US dollar benchmark defining very attractive interventions . Sensitivity analyses on the costs of the ambulance and the rate of effective referrals emphasized the robustness of the result . CONCLUSIONS The cost-effectiveness profile of an ambulance service within a series of interventions aim ed at improving reproductive health in remote setting s is very attractive We did a cost-effectiveness analysis alongside a cluster-r and omised controlled trial of a participatory intervention with women 's groups to improve birth outcomes in rural Nepal . The average provider cost of the women 's group intervention was US0.75 dollars per person per year ( 0.90 dollars with health-service strengthening ) in a population of 86,704 . The incremental cost per life-year saved ( LYS ) was 211 dollars ( 251 dollars ) , and expansion could rationalise on start-up costs and technical assistance , reducing the cost per LYS to 138 dollars ( 179 dollars ) . Sensitivity analysis showed a variation from 83 dollars to 263 dollars per LYS for most variables . This intervention could provide a cost-effective way of reducing neonatal deaths IMPORTANCE Community-based interventions can reduce neonatal mortality when health systems are weak . Population coverage of target groups may be an important determinant of their effect on behavior and mortality . A women 's group trial at coverage of 1 group per 1414 population in rural Bangladesh showed no effect on neonatal mortality , despite a similar intervention having a significant effect on neonatal and maternal death in comparable setting s. OBJECTIVE To assess the effect of a participatory women 's group intervention with higher population coverage on neonatal mortality in Bangladesh . DESIGN A cluster r and omized controlled trial in 9 intervention and 9 control clusters . SETTING Rural Bangladesh . PARTICIPANTS Women permanently residing in 18 unions in 3 districts and accounting for 19 301 births during the final 24 months of the intervention . INTERVENTIONS Women 's groups at a coverage of 1 per 309 population that proceed through a participatory learning and action cycle in which they prioritize issues that affected maternal and neonatal health and design and implement strategies to address these issues . MAIN OUTCOMES AND MEASURES Neonatal mortality rate . RESULTS Analysis included 19 301 births during the final 24 months of the intervention . More than one-third of newly pregnant women joined the groups . The neonatal mortality rate was significantly lower in the intervention arm ( 21.3 neonatal deaths per 1000 live births vs 30.1 per 1000 in control areas ) , a reduction in neonatal mortality of 38 % ( risk ratio , 0.62 [ 95 % CI , 0.43 - 0.89 ] ) when adjusted for socioeconomic factors . The cost-effectiveness was US $ 220 to $ 393 per year of life lost averted . Cause-specific mortality rates suggest reduced deaths due to infections and those associated with prematurity/low birth weight . Improvements were seen in hygienic home delivery practice s , newborn thermal care , and breastfeeding practice s. CONCLUSIONS AND RELEVANCE Women 's group community mobilization , delivered at adequate population coverage , is a highly cost-effective approach to improve newborn survival and health behavior indicators in rural Bangladesh . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N01805825 BACKGROUND Community mobilisation through participatory women 's groups might improve birth outcomes in poor rural communities . We therefore assessed this approach in a largely tribal and rural population in three districts in eastern India . METHODS From 36 clusters in Jharkh and and Orissa , with an estimated population of 228 186 , we assigned 18 clusters to intervention or control using stratified r and omisation . Women were eligible to participate if they were aged 15 - Output:	There was reasonably strong evidence for the cost-effectiveness of the use of women ’s groups , home-based newborn care using community health workers and traditional birth attendants , adding services to routine antenatal care , a facility-based quality improvement initiative to enhance compliance with care st and ards , and the promotion of breastfeeding in maternity hospitals .
MS21870	*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 OBJECTIVE --To examine the effect on mortality of stopping smoking after myocardial infa rct ion and the psychosocial factors that influence the decision to stop . DESIGN -- Analysis of smokers in a large prospect i ve study . Self completed question naires provided information on psychosocial factors . SETTING --Coronary care units at six English hospitals participating in a multicentre clinical trial . SUBJECTS -- These comprised consenting myocardial infa rct ion survivors who had been identified as smokers and who completed question naires within seven days of infa rct at six hospitals participating in the Anglo-Sc and inavian study of early thrombolysis . The 532 patients identified have been followed for over five and a half years . The main outcome measure was five year all cause mortality . MAIN RESULTS --Smokers who stopped within one month showed significantly reduced mortality compared with those who persisted , adjusting for other prognostic indicators ( odds ratio 0.56 , 95 % confidence interval 0.33 , 0.98 ) . Overall , 74 % stopped smoking . Being married , low life stress levels before infa rct , and higher social class were associated with stopping smoking but the differentials were small . Of the clinical variables , a final diagnosis of definite myocardial infa rct ion was associated with stopping smoking . All associations remained after multiple logistic regression . CONCLUSION --Smoking cessation can halve the smokers ' odds of dying after myocardial infa rct ion and psychosocial factors play a small but important role in the important decision to stop smoking . Health professionals should continue to stress the importance of stopping smoking to all patients as there is little evidence to support specific directing of advice to relatively " stress or " socially isolated " groups STUDY OBJECTIVE : To determine the relationship between obesity and subsequent incidence of ischaemic heart disease ( IHD ) . DESIGN : Prospect i ve cohort survey . SETTING : Study of three occupational groups , with follow up examinations . SUBJECTS : 3500 people recruited between 1972 and 1978 ( 80 % response rate ) , and followed up between 1978 and 1984 . This report is based on subgroup of 1511 white men aged 40 - 64 at entry . MEASUREMENTS AND MAIN RESULTS : Information was obtained on smoking and family history of IHD . Blood pressure , weight , height , skinfold thickness at four sites , fibrinogen , factor VII activity and cholesterol were measured during follow up . Body mass index ( BMI ) was used as an index of obesity . BMI was found to be more strongly correlated with IHD than any of the skinfold measurements , none of which was significantly associated with IHD when BMI was allowed for . Increase in BMI by 1 SD ( approximately 8 kg ) was associated with a 44 % increase in the risk of IHD . Of the four skinfolds , subscapular was the most closely associated with risk , confirming the relevance of central obesity . The association between obesity and IHD remained when possible mechanisms for its effects were taken into account , and its strength may increase with time : for 1 SD increase in BMI , risk of events within 5 years was increased by 28 % , while risk of events after longer than 5 years was increased by 65 % . CONCLUSIONS : Preventive strategies for IHD should include avoidance of obesity In the British United Provident Association ( BUPA ) study , a prospect i ve observational study of 21,520 men , the serum albumin of 877 men who died during 10 years of follow-up was compared with that of 877 controls , each matched to a case by age ( within 1 year ) and date of attendance ( within 3 months ) . There was little overall difference ( mean case-control difference = -0.11 milligram , P > 0.2 ) despite the fact that other studies have reported a long-term association between low serum albumin and increased mortality . Cause-specific mortality data showed no association of low albumin with ischaemic heart disease or other circulatory diseases . An inverse association with cancer was confined to the first few years of follow-up and so attributable to pre- clinical cancer lowering both serum albumin itself and serum cholesterol , with which albumin was associated . There was an association of chronic respiratory , neurological , renal , liver and gut diseases with low serum albumin ( case-control difference = -1.19 milligram , P < 0.001 ) consistent with the effect of pre- clinical disease lowering serum albumin . Other causes of death showed no association with albumin . Our data do not support a cause and effect association of low serum albumin and mortality BACKGROUND Previous studies on diet and coronary heart disease ( CHD ) focused primarily on individual nutrients or foods . OBJECTIVE We examined whether overall dietary patterns derived from a food-frequency question naire ( FFQ ) predict risk of CHD in men . DESIGN This was a prospect i ve cohort study of 44875 men aged 40 - 75 y without diagnosed cardiovascular disease or cancer at baseline in 1986 . RESULTS During 8 y of follow-up , we documented 1089 cases of CHD ( nonfatal myocardial infa rct ion and fatal CHD ) . Using factor analysis , we identified 2 major dietary patterns using dietary data collected through a 131-item FFQ . The first factor , which we labeled the " prudent pattern , " was characterized by higher intake of vegetables , fruit , legumes , whole grains , fish , and poultry , whereas the second factor , the " Western pattern , " was characterized by higher intake of red meat , processed meat , refined grains , sweets and dessert , French fries , and high-fat dairy products . After adjustment for age and CHD risk factors , the relative risks from the lowest to highest quintiles of the prudent pattern score were 1.0 , 0 . 87 , 0.79 , 0.75 , and 0.70 ( 95 % CI : 0.56 , 0.86 ; P : for trend = 0.0009 ) . In contrast , the relative risks across increasing quintiles of the Western pattern score were 1.0 , 1.21 , 1.36 , 1.40 , and 1.64 ( 95 % CI : 1.24 , 2.17 ; P : for trend < 0.0001 ) . These associations persisted in subgroup analyses according to cigarette smoking , body mass index , and parental history of myocardial infa rct ion . CONCLUSIONS These data suggest that major dietary patterns derived from the FFQ predict risk of CHD , independent of other lifestyle variables Editorial by Jackson Current guidelines for prescribing lipid lowering drugs are based on an individual 's risk of coronary heart disease rather than on the reduction in risk that treatment may bring . We report a strategy for making treatment decisions that combines computer assisted calculation of absolute risk with an estimate of benefit to the patient from treatment . During a period of 14 months , 17 r and omly selected general practice s ( 63 practitioners ) in north Staffordshire were asked to send to the department of clinical biochemistry their requests for coronary heart disease risk assessment on patients being considered for lipid lowering drug treatment . Coronary risk factors in patients being considered for lipid lowering drugs . Values are means ( SD ) We used the Framingham statistical model to estimate a patient 's absolute risk of coronary heart disease over five years . The reduction in risk that treatment would bring over the next five years was calculated from the product of the absolute five OBJECTIVE : To investigate the associations of individual and area-based socioeconomic indicators with cardiovascular disease risk factors and mortality . DESIGN : Prospect i ve study . SETTING : The towns of Renfrew and Paisley in the west of Scotl and . PARTICIPANTS : 6961 men and 7991 women included in a population -based cardiovascular disease screening study between 1972 and 1976 . MAIN OUTCOME MEASURES : Cardiovascular disease risk factors and cardiorespiratory morbidity at the time of screening : 15 year mortality from all causes and cardiovascular disease . RESULTS : Both the area-based deprivation indicator and individual social class were associated with generally less favourable profiles of cardiovascular disease risk factors at the time of the baseline screening examinations . The exception was plasma cholesterol concentration , which was lower for men and women in manual social class groups . Independent contributions of area-based deprivation and individual social class were generally seen with respect to risk factors and morbidity . All cause and cardiovascular disease mortality rates were both inversely associated with socioeconomic position whether indexed by area-based deprivation or social class . The area-based and individual socioeconomic indicators made independent contributions to mortality risk . CONCLUSIONS : Individually assigned and area-based socioeconomic indicators make independent contributions to several important health outcomes . The degree of inequalities in health that exist will not be demonstrated in studies using only one category of indicator . Similarly , adjustment for confounding by socioeconomic position in aetiological epidemiological studies will be inadequate if only one level of indicator is used . Policies aim ed at reducing socioeconomic differentials in health should pay attention to the characteristics of the areas in which people live as well as the characteristics of the people who live in these areas Abstract Objective : To investigate the association between birth weight of offspring and mortality among fathers and mothers in the west of Scotl and . Design : Prospect i ve observational study . Participants : 794 married couples in Renfrew district of the west of Scotl and . Main outcome measures : Mortality from all causes and from cardiovascular disease over 15 year follow up . Results : Women who had heavier babies were taller , had higher body mass index and better lung function , and were less likely to be smokers than mothers of lighter babies . Fathers of heavier babies were taller and less likely to be smokers than fathers of lighter babies . Mortality was inversely related to offspring 's birth weight for both mothers ( relative rate for a 1 kg lower birth weight 1.82 ( 95 % confidence interval 1.23 to 2.70 ) ) and fathers ( relative rate 1.35 ( 1.03 to 1.79 ) ) . For mortality from cardiovascular disease , inverse associations were seen for mothers ( 2.00 ( 1.18 to 3.33 ) ) and fathers ( 1.52 ( 1.03 to 2.17 ) ) . Adjustment for blood pressure , plasma cholesterol , body mass index , height , social class , area based deprivation category , smoking , lung function , angina , bronchitis , and electrocardiographic evidence of ischaemia had little effect on these risk estimates , although levels of statistical significance were reduced . Conclusions : Birth weight of offspring was related inversely to mortality , from all causes and cardiovascular disease , in this cohort . The strength of this association was greater than would have been expected by the degree of concordance of birth weights across generations , but an extensive range of potential confounding factors could not account for the association . Mortality is therefore influenced by a factor related to birth weight that is transmissible across generations . Key messages Low birth weight is associated with increased mortality from cardiovascular disease in later life , and birth weight is associated across generations so that both maternal and paternal birth weights are associated with the offspring 's birth weight In this observational study we found that lower birth weight of offspring was associated with higher parental mortality from all causes and from cardiovascular disease This elevated mortality could not be explained by a range of social , environmental , behavioural , and physiological risk factors The strength of the association was greater than would have been expected by the degree of concordance of birth weights across generations We conclude that mortality is influenced by a factor that is related to birth weight and is transmissible across In prospect i ve studies , disease rates during follow-up are typically analyzed with respect to the values of factors measured during an initial baseline survey . However , because of " regression dilution , " this generally tends to underestimate the real associations of disease rates with the " usual " levels of such risk factors during some particular exposure period . The " regression dilution ratio " describes the ratio of the steepness of the uncorrected association to that of the real association . To assess the relevance of the usual value of a risk factor during particular exposure periods ( e.g. , first , second , and third decades ) to disease risks , regression dilution ratios can be derived by relating baseline measurements of the risk factor to replicate measurements from a reasonably representative sample of study participants after an interval equivalent to about the midpoint of each exposure period ( e.g. , at 5 , 15 , and 25 years , respectively ) . This report illustrates the impact of this time interval on the magnitude of the regression dilution ratios for blood pressure and blood cholesterol . The analyses were based on biennial re measurements over 30 years for participants in the Framingham Study ( Framingham , Massachusetts ) and a 26-year resurvey for a sample of men in the Whitehall Study ( London , Engl and ) . They show that uncorrected associations of disease risk with baseline measurements underestimate the strength of the real associations with usual levels of these risk factors during the first decade of exposure by about one-third , the second decade by about one-half , and the third decade by about two-thirds . Hence , to correct appropriately for regression dilution , replicate measurements of such risk factors may be required at varying intervals after baseline for at least a sample of participants Abstract Objective : To determine the association between adverse psychosocial characteristics at work and risk of coronary heart disease among male and female civil servants . Design : Prospect i ve cohort study ( Whitehall II study ) . At the baseline examination ( 1985 - 8 ) and twice during follow up a self report question naire provided information on psychosocial factors of the work environment and coronary heart disease . Independent assessment s of the work environment were obtained from personnel managers at baseline . Mean length of follow up was 5.3 years Output:	‘ Early ’ cohorts were important in defining the major risk factors for CHD , particularly smoking , cholesterol , blood pressure , physical activity and body mass index . Conclusions The current and proposed prospect i ve UK cohorts have sufficient power potentially to determine the importance of many traditional and newer CHD risk factors on cardiovascular risk in men , women and even ethnic minorities .
MS21871	*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 Adjuvant chemotherapy is associated with poor quality of life ( qol ) in breast cancer patients . We tested the effect of listening to music during chemotherapy on quality of life in these patients . MATERIAL / METHODS We tested in a prospect i ve cohort the changes in qol scores as assessed by European Organization for Research and Treatment of Cancer Quality of Life Question naire ( EORTC QLQ-C30 ) , and the influence of listening to non-preferred music at the chemotherapy unit on these parameters in a mixed linear model by repeated measures analysis of variance ( RMANOVA ) . RESULTS For the whole cohort , musical intervention was not associated with a change in any dimension of quality of life . However ; the music effect significantly interacted with patient age ; patients > 45 years old had improved insomnia and appetite loss scores after musical intervention ( F = 6.76 , P = 0.019 and F = 11.22 , P = 0.004 , respectively ) . CONCLUSIONS Our results show that brief , non-preferred music exposure at the time of chemotherapy administration does not improve quality of life in patients with early breast cancer . Nonetheless , there is still a possibility that a subgroup will benefit from this approach as suggested by the interaction of the music effect with patient age The treatment of pain continues to gain in saliency as a component of defining best practice in medical care . Music therapy is an integrative treatment modality that impacts patient outcomes in the treatment of spinal pain . At Mount Sinai Beth Israel , we conducted a mixed- methods study addressing the effects of music therapy interventions on the recovery of patients after spine surgery . The study combined st and ard medical approaches and integrative music therapy . Sixty patients ( 35 female , 25 male ) ranging in age from 40 to 55 years underwent anterior , posterior , or anterior-posterior spinal fusion and were r and omly assigned to either music therapy plus st and ard care ( medical and nursing care with scheduled pharmacologic pain intervention ) or st and ard care only . Measurements for both groups were completed before and after the intervention . Music therapy involved the use of patient-preferred live music that supported tension release/relaxation through incentive-based clinical improvisation , singing , and /or rhythmic drumming or through active visualization supported by live music that encompasses tension resolution . The control and music groups showed significant differences in degree and direction of change in the visual analog scale ( VAS ) pain ratings from before to after intervention ( P = .01 ) . VAS pain levels increased slightly in the control group ( to 5.87 from 5.20 ) but decreased by more than 1 point in the music group ( to 5.09 from 6.20 ) . The control and music therapy groups did not differ in the rate of change in scores on Hospital Anxiety and Depression Scale ( HADS ) Anxiety ( P = .62 ) , HADS Depression ( P = .85 ) , or Tampa Scale for Kinesiophobia ( P = .93 ) . Both groups had slight increases in HADS Anxiety , comparable decreases in HADS Depression , and minimal changes in fear-related movement ( Tampa scale ) Goals of workPrevention of chemotherapy-induced nausea and vomiting ( CINV ) with st and ard antiemetics has been more difficult to achieve in female patients . Data from two phase III trials of the NK1 antagonist aprepitant were assessed for potential effect of gender on treatment response . Patients and methods 1,044 patients receiving cisplatin ( ≥70 mg/m2 ) were r and omly assigned to control regimen [ ondansetron ( O ) 32 mg i.v . and dexamethasone ( D ) 20 mg p.o . on day 1 ; D 8 mg twice daily on days 2–4 ] or aprepitant ( A ) regimen ( A 125 mg p.o . plus O 32 mg and D 12 mg on day 1 ; A 80 mg and D 8 mg once daily on days 2–3 ; and D 8 mg on day 4 ) . The primary endpoint was overall complete response ( no emesis and no rescue therapy over days 1–5 ) . Data were analyzed by a modified intent-to-treat approach . Between-treatment comparisons for each gender were made using logistic regression . Main results Women comprised 42 and 43 % of the aprepitant and control groups , respectively . In the control group , 41 % of women had overall complete response compared with 53 % of men . In the aprepitant group , 66 % of women had overall complete response compared with 69 % of men . Conclusion The addition of aprepitant may negate the adverse prognostic effect of female gender on the prevention of CINV in patients receiving highly emetogenic chemotherapy PURPOSE To examine the effect of patient-selected music intervention during daily weaning trials for patients on prolonged mechanical ventilation . METHODS Using a crossover repeated measures design , patients were r and omized to music vs no music on the first intervention day . Provision of music was alternated for 6 days , result ing in 3 music and 3 no music days . During weaning trials on music days , data were obtained for 30min prior to music listening and continued for 60min while patients listened to selected music ( total 90min ) . On no music days , data were collected for 90min . Outcome measures were heart rate ( HR ) , respiratory rate ( RR ) , oxygen saturation ( SpO2 ) , blood pressure ( BP ) , dyspnea and anxiety assessed with a visual analog scale ( VAS-D , VAS-A ) and weaning duration ( meanh per day on music and non-music days ) . RESULTS Of 31 patients r and omized , 23 completed the 6-day intervention . When comparisons were made between the 3 music and 3 no music days , there were significant decreases in RR and VAS-D and a significant increase in daily weaning duration on music days ( p<0.05 ) . A multivariate mixed-effects model analysis that included patients who completed ≥2 days of the intervention ( n=28 ) demonstrated significant decreases in HR , RR , VAS-A , and VAS-D and a significant increase in daily weaning duration on music days ( p<0.05 ) . CONCLUSIONS Providing patient selected music during daily weaning trials is a simple , low-cost , potentially beneficial intervention for patients on prolonged mechanical ventilation . Further study is indicated to test ability of this intervention to promote weaning success and benefits earlier in the weaning process PURPOSE / OBJECTIVES To test whether use of music as a diversional intervention during high-dose chemotherapy administration would affect perception of nausea and episodes of vomiting . SAMPLE 39 patients undergoing bone marrow transplant . A total of 33 patients were included in the data analysis , with 17 in the control group and 16 in the music intervention group . METHODS Patients were assigned r and omly to a control group ( usual antiemetic protocol ) or the experimental group ( usual antiemetic group plus music intervention during the 48 hours of high-dose cyclophosphamide administered as part of the preparative regimen ) . MAIN RESEARCH VARIABLES Use of a music intervention , perception of nausea , and instances of vomiting . FINDINGS Significant differences were found between group scores on a visual analog scale for nausea and number of episodes of vomiting , demonstrating that the experimental group experienced less nausea and fewer instances of vomiting . CONCLUSION This study found that music is an effective adjunct to a pharmacologic antiemetic regimen for lessening nausea and vomiting , and this study merits further investigation through a larger multi-institutional effort . IMPLICATION S FOR NURSING PRACTICE Using music as a diversional adjunct intervention to antiemetic therapy is helpful in decreasing nausea and vomiting . The intervention can be initiated independently by nurses and individualized for each patient , leading to greater patient comfort and compliance with high-dose chemotherapy Purpose Despite significant advances in antiemetic management , almost 50 % of cancer patients still experience nausea and vomiting during treatment . The goal of antiemetic therapy is complete prevention of treatment-induced nausea and /or vomiting ( TINV ) ; however , realisation of this goal remains elusive , thus supplementary strategies identifying patients at high risk must be employed in the interim . Consequently , we examined TINV incidence and its risk factors , including patient , clinical and pretreatment quality of life (QOL)/psychological factors . Methods Two hundred newly diagnosed cancer patients beginning combined treatment participated in this prospect i ve , longitudinal , observational study . QOL ( including TINV ) , psychological adjustment , and patient/ clinical characteristics were examined at pretreatment , on-treatment ( 8 weeks ± 1 week ) and post-treatment . Results Overall , 62 % of patients experienced TINV , with TIN incidence ( 60 % ) doubling that of TIV ( 27 % ) . Eight independent risk factors predicted 73 % of TIN incidence : high premorbid/anticipatory NV , moderately/highly emetogenic chemotherapy ( M/HEC ) , longer treatment ( > 3 months ) , female gender , surgery prior to adjuvant chemotherapy ± radiotherapy , private health insurance and low emotional functioning ( pretreatment ) . Six independent risk factors predicted 77 % of TIV incidence : premorbid/anticipatory vomiting , M/HEC , female gender , cancer resection and low role functioning ( pretreatment ) . Conclusions TINV still represents a very major concern for patients . Several pretreatment risk factors for the development of TIN and TIV , respectively , were identified . Patients about to undergo cancer treatment , particularly combined treatment involving emetogenic chemotherapy and surgery , should be screened for these factors with a view to modifying st and ard pretreatment/maintenance antiemetic therapy . Furthermore , and consistent with recent research , it is recommended that more comprehensive interventions combining antiemetics with other effective pharmacological ( e.g. anxiolytics ) and non-pharmacological approaches ( e.g. acupuncture , relaxation techniques ) be considered by clinicians in attempts to improve control of TIN and TIV ( and overall QOL ) for their patients . In this way , optimal holistic care will be ensured for cancer patients by clinicians providing conventional oncology treatment PURPOSE Pharmacological therapy is only partially effective in preventing or treating chemotherapy induced nausea and vomiting ( CINV ) . Therefore , exploring the complementary role of non-pharmacological approaches used in addition to pharmacological agents is important . Nevasic uses specially constructed audio signals hypothesized to generate an antiemetic reaction . The aim of this study was to examine the feasibility of conducting a r and omized controlled trial ( RCT ) to evaluate the effectiveness of Nevasic to control CINV . METHODS A mixed methods design incorporating an RCT and focus group interviews . For the RCT , female breast cancer patients were r and omized to receive either Nevasic plus usual care , music plus usual care , or usual care only . Data were analysed using descriptive statistics and linear mixed-effects models . Five focus group interviews were conducted to obtain participants ' views regarding the acceptability of the interventions in the trial . RESULTS 99 participants were recruited to the RCT and 15 participated in focus group interviews . Recruitment targets were achieved . Issues of Nevasic acceptability were highlighted as weaknesses of the program . This study did not detect any evidence for the effectiveness of Nevasic ; however , the results showed statistically significant less use of anti-emetics ( p = 0.003 ) and borderline non-significant improvement in quality of life ( p = 0.06 ) . CONCLUSIONS Conducting a non-pharmacological intervention using such an audio program is feasible , although difficulties and limitations exist with its use . Further studies are required to investigate the effectiveness of Nevasic from perspectives such as anti-emetic use , as well as its overall effect on the levels of nausea and vomiting Goals of workA number of prognostic factors have been identified as risk factors for chemotherapy-induced emesis . This post-hoc analysis addressed whether : ( 1 ) these prognostic factors can identify a low-risk group for whom ondansetron plus dexamethasone alone provide a high level of protection ( ≥80 % no emesis ) ; ( 2 ) the NK1 receptor antagonist aprepitant improves antiemetic outcome regardless of emetic risk . Patients and methods Breast cancer patients in a phase III double-blind , placebo-controlled trial were r and omized to antiemetic regimens including ondansetron and dexamethasone , or aprepitant , ondansetron , and dexamethasone . Multivariate logistic regression models were used to assess the impact on emesis ( but not nausea ) of the regimen with aprepitant , and previously reported risk factors , including age ( < 55 and ≥55 years ) , ethanol use ( 0–4 or ≥5 drinks/week ) , history of pregnancy-related morning sickness , and history of motion sickness , using a modified intent-to-treat approach . Results Treatment with aprepitant ( P < 0.0001 ) , older age ( P = 0.006 ) , ethanol use ( P = 0.0048 ) , and no history of morning sickness ( P = 0.0007 ) were all significantly associated with reduced likelihood of emesis . The proportion of patients with one , two , or three risk factors who remained emesis free was significantly higher with the aprepitant-containing regimen than with the active control ( 70.2–82.8 % vs. 38.6–66.4 % , respectively ) . Conclusions Aprepitant markedly improved control of emesis in patients with one or more risk factors . This analysis did not support using risk factors for modifying the antiemetic approach . A low-risk group with zero risk factors for whom aprepitant provided little benefit was Output:	Locus of control for music selection was more often with the investigator rather than the participant . IMPLICATION S FOR RESEARCH The existing data have been largely generated by nurse scientists , and implication s for nursing practice are many , because music interventions are low-cost , easily accessible , and without known adverse effects .
MS21872	*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 : Despite thous and s of papers , the value of quality of life ( QoL ) in curing disease remains uncertain . Until now , we lacked tools for the diagnosis and specific treatment of diseased QoL. We approached this problem stepwise by theory building , modelling , an exploratory trial and now a definitive r and omised controlled trial ( RCT ) in breast cancer , whose results we report here . Methods : In all , 200 representative Bavarian primary breast cancer patients were recruited by five hospitals and treated by 146 care professionals . Patients were r and omised to either ( 1 ) a novel care pathway including diagnosis of ‘ diseased ’ QoL ( any QoL measure below 50 points ) using a QoL profile and expert report sent to the patient 's coordinating practitioner , who arranged QoL therapy consisting of up to five st and ardised treatments for specific QoL defects or ( 2 ) st and ard postoperative care adhering to the German national guideline for breast cancer . The primary end point was the proportion of patients in each group with diseased QoL 6 months after surgery . Patients were blinded to their allocated group . Results : At 0 and 3 months after surgery , diseased QoL was diagnosed in 70 % of patients . The QoL pathway reduced rates of diseased QoL to 56 % at 6 months , especially in emotion and coping , compared with 71 % in controls ( P=0.048 ) . Relative risk reduction was 21 % ( 95 % confidence interval ( CI ) : 0–37 ) , absolute risk reduction 15 % ( 95 % CI : 0.3–29 ) , number needed to treat (NNT)=7 ( 95 % CI : 3–37 ) . When QoL therapy finished after successful treatment , diseased QoL often returned again , indicating good responsiveness of the QoL pathway . Conclusion : A three-component outcome system including clinician-derived objective , patient-reported subjective end points and qualitative analysis of clinical relevance was developed in the last 10 years for cancer as a complex intervention . A separate QoL pathway was implemented for the diagnosis and treatment of diseased QoL and its effectiveness tested in a community-based , pragmatic , definitive RCT . While the pathway was active , it was effective with an NNT of 7 PURPOSE To examine the effect of weekly completion of a patient-held quality -of-life ( QOL ) diary in routine oncology practice for palliative care patients . PATIENTS AND METHODS In a pragmatic r and omized controlled trial , 115 patients with inoperable lung cancer were r and omly assigned to receive either st and ard care or a structured QOL diary ( European Organisation for Research and Treatment of Cancer Quality of Life Question naire C30 and the related lung cancer module LC13 ) that they completed at home each week for 16 weeks . Patients were encouraged to share the QOL information with health professionals involved in their care . Changes in QOL over time ( measured by the Functional Assessment of Cancer Therapy-Lung question naire and the Palliative Care Quality of Life Index ) , discussion of patient problems , and satisfaction with communication and general care were assessed at baseline and at 2 and 4 months after baseline . RESULTS Analysis of QOL indicated a small but consistent difference between patients in the diary group and the st and ard care group . The diary group had a poorer QOL in many domains . Two different QOL summary scores ( total and overall QOL ) indicated a statistically significant between-group difference . No effects were found in relation to satisfaction with care , communication , or the discussion of patient problems . CONCLUSION The regular completion of a QOL question naire without appropriate feedback to health care professionals and without the provision of appropriate support may have a negative impact on inoperable lung cancer patients . Further research should focus on identifying features such as feedback loops that are required for the successful and meaningful use of QOL question naires in routine patient care 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 PURPOSE Although psychosocial intervention can reduce psychosocial distress following breast cancer , many women who are experiencing problems are not identified and offered additional help . This trial assessed effects on quality of life of psychologic distress screening among newly diagnosed , nonmetastatic breast cancer patients . PATIENTS AND METHODS From 1990 to 1992 , all eligible patients in one regional breast cancer center were identified and offered study participation . Women in both control and experimental groups received brief psychosocial intervention from a social worker at initial treatment . The experimental group also had monthly telephone screening of distress levels using a brief , vali date d instrument , with additional psychosocial intervention offered only to those with high distress at screening . RESULTS Among 282 eligible patients , 89 % were r and omized and completed the study . Participants ' psychologic distress levels decreased over the study period ( P = .0001 ) . However , no between-group differences were observed . Mean distress scores among control and experimental women at 0- , 3- , and 12-month interviews were 20.7 and 20.4 , 15.5 and 15.0 , and 14.6 and 13.5 , respectively . No between-group differences were observed with respect to physical health , functional status , social and leisure activities , return to work , or marital satisfaction . CONCLUSION Our results indicate that , among patients who receive a minimal psychosocial intervention as part of their initial cancer care , a distress screening program does not improve quality of life . Minimal psychosocial intervention at initial treatment may be effective in reducing distress , thus making it difficult to obtain additional benefit from a screening program PURPOSE Although patient-reported cancer symptoms and quality -of-life issues ( SQLIs ) have been promoted as essential to a comprehensive assessment , efficient and efficacious methods have not been widely tested in clinical setting s. The purpose of this trial was to determine the effect of the Electronic Self-Report Assessment -Cancer ( ESRA-C ) on the likelihood of SQLIs discussed between clinicians and patients with cancer in ambulatory clinic visits . Secondary objectives included comparison of visit duration between groups and usefulness of the ESRA-C as reported by clinicians . PATIENTS AND METHODS This r and omized controlled trial was conducted in 660 patients with various cancer diagnoses and stages at two institutions of a comprehensive cancer center . Patient-reported SQLIs were automatically displayed on a graphical summary and provided to the clinical team before an on-treatment visit ( n = 327 ) ; in the control group , no summary was provided ( n = 333 ) . SQLIs were scored for level of severity or distress . One on-treatment clinic visit was audio recorded for each participant and then scored for discussion of each SQLI . We hypothesized that problematic SQLIs would be discussed more often when the intervention was delivered to the clinicians . RESULTS The likelihood of SQLIs being discussed differed by r and omized group and depended on whether an SQLI was first reported as problematic ( P = .032 ) . Clinic visits were similar with regard to duration between groups , and clinicians reported the summary as useful . CONCLUSION The ESRA-C is the first electronic self-report application to increase discussion of SQLIs in a US r and omized clinical trial 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 Objectives To evaluate the impact of a mobile phone-based , remote monitoring , advanced symptom management system ( ASyMS © ) on the incidence , severity and distress of six chemotherapy-related symptoms ( nausea , vomiting , fatigue , mucositis , h and –foot syndrome and diarrhoea ) in patients with lung , breast or colorectal cancer . Design A two group ( intervention and control ) by five time points ( baseline , pre-cycle 2 , pre-cycle 3 , pre-cycle 4 and pre-cycle 5 ) r and omised controlled trial . Setting Seven clinical sites in the UK ; five specialist cancer centres and two local district hospitals . Participants One hundred and twelve people with breast , lung or colorectal cancer receiving outpatient chemotherapy . Interventions A mobile phone-based , remote monitoring , advanced symptom management system (ASyMS © ).Main outcome measures Chemotherapy-related morbidity of six common chemotherapy-related symptoms ( nausea , vomiting , fatigue , mucositis , h and –foot syndrome and diarrhoea ) . Results There were significantly higher reports of fatigue in the control group compared to the intervention group ( odds ratio = 2.29 , 95%CI = 1.04 to 5.05 , P = 0.040 ) and reports of h and –foot syndrome were on average lower in the control group ( odds ratio control/intervention = 0.39 , 95%CI = 0.17 to 0.92 , P = 0.031 ) . Conclusion The study demonstrates that ASyMS © can support the management of symptoms in patients with lung , breast and colorectal cancer receiving chemotherapy The potential benefits of health-related quality of life ( HRQL ) assessment in oncology clinical practice include better detection of problems , enhanced disease and treatment monitoring and improved care . However , few empirical studies have investigated the effects of incorporating such assessment s into routine clinical care . Recent r and omized studies have reported improved detection of and communication about patients ' concerns , but few have found effects on patient HRQL or satisfaction . This study examined whether offering interpretive assistance of HRQL results would improve these patient outcomes . Two hundred and thirteen participants with metastatic breast , lung or colorectal cancer were r and omly assigned to one of three conditions : usual care ; HRQL assessment or HRQL assessment followed by a structured interview and discussion . Interviews about patients ' assessment responses were conducted by a research nurse , who then presented HRQL information to the treating nurse . HRQL and treatment satisfaction outcomes were assessed at 3 and 6 months . No significant differences were found between study conditions in HRQL or satisfaction . Results suggest that routine HRQL assessment , even with description of results , is insufficient to improve patient HRQL and satisfaction . It is suggested that positive effects may require supplementing assessment results with specific suggestions for clinical management changes OBJECTIVE To examine the effects of a computer-assisted , interactive tailored patient assessment ( ITPA ) tool in oncology practice on : documented patient care , symptom distress , and patients ' need for symptom management support during treatment and rehabilitation . DESIGN AND METHODS For this repeated measures clinical trial at a university hospital in Norway , 145 patients starting treatment for leukemia or lymphoma were r and omly assigned to either an intervention ( n=75 ) or control group ( n=70 ) . Both groups used the ITPA for symptom assessment s prior to inpatient and outpatient visits for up to one year . The assessment summary , which displayed patients ' self-reported symptoms , problems , and distress in rank-order of the patient 's need for support , was provided to physicians and nurses in the intervention group only but not in the control group . RESULTS Significantly more symptoms were addressed in the intervention group patient charts versus those of the control group . Symptom distress in the intervention group decreased significantly over time in 11 ( 58 % ) of 19 symptom/problem categories versus 2 ( 10 % ) for the control group . Need for symptom management support over time also decreased significantly more for the intervention group than the control group in 13 ( 68 % ) symptom categories . CONCLUSION This is the first study to show that an ITPA used in an interdisciplinary oncology practice can significantly improve patient-centered care and patient outcomes , including reduced symptom distress and reduced need for symptom management support BACKGROUND Menopausal symptoms ( e.g. , hot flashes , vaginal dryness , and stress urinary incontinence ) are very common in breast cancer survivors and can not be managed with st and ard estrogen replacement therapy ( ERT ) in Output:	Overall , the number of statistically significant findings were limited and PROMs ' intervention effect sizes were predominantly small-to-moderate . The routine use of PROMs increases the frequency of discussion of patient outcomes during consultations . In some studies , PROMs are associated with improved symptom control , increased supportive care measures , and patient satisfaction .
MS21873	*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 All-ceramic resin-bonded fixed partial dentures ( RBFPDs ) were introduced as a conservative treatment approach 15 years ago . The purpose of this prospect i ve study was to evaluate the long-term clinical survival of RBFPDs made with a conventional two-retainer design or a cantilever single-retainer design . METHOD AND MATERIAL S A total of 37 anterior RBFPDs were made from the glass-infiltrated alumina ceramic In-Ceram . Sixteen RBFPDs with a conventional two-retainer design were inserted in 14 patients , and 21 RBFPDs with a cantilever single-retainer design were inserted in 16 patients . Panavia or Panavia 21 were used as luting agents either after silica-coating and silanation or after air-abrasion only . Patients were recalled every year for a clinical examination to evaluate the restorations with regard to function and possible failures . The mean observation time in the two-retainer group was 75.8 months , and in the single-retainer group it was 51.7 months . RESULTS No restoration debonded . In the two-retainer group , one restoration was lost because it fractured after 3 months at both connectors and one restoration was removed alio loco accidentally . Also in this group , four RBFPDs fractured within 15 months after insertion at one connector , but the pontic remained in situ as a cantilever RBFPD for several years . In the single-retainer group , only one FPD fractured and was lost 48 months after insertion . The 5-year survival rate was 73.9 % in the two-retainer group and 92.3 % in the single-retainer group . When unilateral fracture of a FPD was taken as criterion for failure , the five-year survival rate decreased to 67.3 % in the two-retainer group . CONCLUSIONS Cantilever all-ceramic resin-bonded fixed partial dentures made from high-strength oxide ceramics present a promising treatment alternative to two-retainer RBFPDs in the anterior region OBJECTIVES The purpose of this clinical study was to evaluate the long-term outcome of 3-unit anterior fixed partial dentures ( FPDs ) made of fiber-reinforced resin composite ( FRC ) , and to identify design factors influencing the survival rate . METHODS 52 patients ( 26 females , 26 males ) received 60 indirectly made FRC FPDs , using pre-impregnated unidirectional glass fibers , requiring manual wetting , as framework material . FPDs were surface ( n=48 ) or hybrid ( n=12 ) retained and mainly located in the upper jaw . Hybrid FPDs had a combination of retainers ; i.e. crown at one and surface retention at the other abutment tooth . Surface FPDs were either purely adhesively retained ( n=29 ) or with additional mechanical retention ( n=19 ) . Follow-up period was at minimum 5 years , with check-ups every 1 - 2 years . Six operators were involved , in three centers in the Netherl and s , Finl and and Sweden . Survival rates , including repairable defects of FPDs , and success rates were determined . RESULTS Kaplan-Meier survival rate at 5 years was 64 % ( SE 7 % ) . For the level of success , values were 45 % ( SE 7 % ) and the estimated median survival time 58 ( SE 10.1 ) months . For surface FPDs , additional mechanical retention did not improve survival significantly . There was a trend towards better survival of surface FPDs over hybrid FPDs , but differences were not significant . Main failure modes were fracture of the FPD and delamination of veneering composite . SIGNIFICANCE A success rate of 45 % and a survival rate of 64 % after 5 years was found . Fracture of the framework and delamination are the most prevalent failure modes , especially for surface FPDs OBJECTIVES This prospect i ve clinical study evaluated the performance of indirect , anterior , surface-retained , fibre-reinforced-composite restorations ( ISFRCR ) . METHODS Between June-2003 and January-2011 , a total of 134 patients ( 83 females , 51 males , 16 - 68 years old ) received 175 ISFRCRs ( local ethical registration number : 14/9/4 ) . All restorations were made indirectly on a plaster model using unidirectional E-glass fibres ( everStick C&B , StickTech ) in combination with a laboratory resin composite ( Dialogue , Schütz Dental ) and cemented according to the instructions of 4 resin cements [ ( RelyX ARC , 3M-ESPE , n=61 ) , Bifix DC , VOCO , n=45 ) , Variolink II ( Ivoclar Vivadent , n=32 ) and Multilink ( Ivoclar Vivadent , n=37 ) ] . After baseline recordings , patients were followed at 6 months and thereafter annually up to 7.5 years . The evaluation protocol involved technical ( chipping , debonding or fracture of tooth/restoration ) and biological failures ( caries ) . RESULTS Mean observation period was 58 months . Altogether , 13 failures were observed [ survival rate : 97.7 % ] ( Kaplan-Meier ) . One catastrophic fracture [ ( cement : RelyX ARC ) , eight partial debonding ( cement : Bifix DC ( 5 ) , Multilink ( 1 ) , RelyX ARC ( 1 ) , Variolink II ( 1 ) ] and four delaminations of veneering composite [ ( cement : Bifix DC ( 2 ) , RelyX ARC ( 1 ) , Multilink ( 1 ) ] were observed . Except one replacement , all defective restorations were repaired or recemented . Annual failure rate of ISFRCRs was 1.73 % . The survival rates with the four resin cements did not show significant differences ( RelyX ARC : 98.3 % ; Bifix DC : 93.5 % ; Variolink 2 : 100 % ; Multilink : 100 % ) ( p=0.114 ) . Secondary caries did not occur in any of the teeth . CONCLUSION The 3-unit anterior indirect surface-retained resin-bonded FRC FDPs showed similar clinical survival rate when cemented with the resin cements tested . Experienced failures in general were due to debonding of the restoration or delamination of the veneering composite . CLINICAL SIGNIFICANCE 3-unit surface retained resin-bonded FRC FDPs could be considered minimal invasive and cost-effective alternatives to conventional tooth- or implant-borne FDPs . Failures were mainly repairable in the form of chipping or debonding depending on the resin cement type PURPOSE To retrospectively evaluate the 6-year survival rates and technical/ biologic complication rates of single-retainer glass-ceramic resin-bonded fixed dental prostheses ( RBFDPs ) . MATERIAL S AND METHODS Forty patients with 49 anterior/posterior glass-ceramic RBFDPs were included . The RBFDPs replaced 11 maxillary/m and ibular central incisors , 18 lateral incisors , 18 premolars , and 2 molars . Patients willing to participate were clinical ly and radiologically examined . The technical outcome was assessed with modified United States Public Health Service criteria . Fracture and /or chipping of the restoration , occlusal wear , marginal adaptation , marginal discoloration , shape , surface texture , and esthetic integration were recorded . Tooth vitality and postoperative sensitivity were tested . The following biologic parameters were assessed at test and control teeth : probing pocket depth , gingival recession , attachment loss , bleeding on probing , furcation involvement , and periodontal mobility . Statistical analysis was performed with exact 95 % confidence intervals to relative frequencies and the paired t test . RESULTS Twenty-eight patients with 35 RBFDPs participated . The mean follow-up of the RBFDPs was 6 years . Twelve patients with 14 RBFDPs were not willing to participate or not available . No catastrophic failures occurred . The 6-year survival rate of the examined RBFDPs was 100 % . No debonding was recorded . Chipping of the ceramic was found in 5.7 % of the RBFDPs . Biologic outcomes were similar at test and control teeth . CONCLUSION Glass-ceramic RBFDPs exhibited promising clinical outcomes in both anterior and posterior regions Previous clinical observations have revealed that resin-bonded bridges for posterior tooth replacements are less retentive than anterior resin-bonded bridges . Improved bonding procedures and preparation design s , however , may have a positive effect on the functional durability of these restorations . The present study reports the final analysis of a r and omized controlled clinical trial in which different design s of posterior resin-bonded bridges were evaluated for a period of at least 5 years . The operational hypothesis was that the bonding system and the preparation design used in posterior resin-bonded bridges have an influence on the survival and clinical functioning of these restorations . Survival in this study was defined at two levels : ( 1 ) ' complete ' survival ( survival without any debonding ) , and ( 2 ) ' functional ' survival ( survival including loss of retention on one occasion and successful rebonding of the original RBB without further debonding ) . With regard to ' complete ' survival , no significant differences were found between the bonding systems used for adherence of the restorations to abutment teeth ( etching/Clearfil F2 , s and blasting/Panavia EX , and silica-coating/Microfill Pontic C ) . The variable ' preparation form ' ( conventional preparation form vs. modified preparation form ) for complete survival was statistically in favor of the modified preparation form ( 62 % vs. 46 % ) , but did not influence the functional survival . With regard to ' functional ' survival , the combination of silica coating and Microfill Pontic C was more retentive than the other bonding systems ( 90 % survival vs. 72 % and 75 % , p < 0.01 ) . Factor location was found to be highly significant for both survival levels [ Cox 's PH model , p = 0.0002 ( Cox , 1972 ) ] : The five-year ' complete ' survival rates were 65 % for maxillary restorations and 40 % for m and ibular restorations , while the five-year ' functional ' survival rates were 89 % and 68 % , respectively . It is concluded that preparation of grooves in abutment teeth for posterior resin-bonded bridges is beneficial to their chance of survival . Resin-bonded bridges placed in the maxilla have a better prognosis than those made in the m and ible . The bonding systems used in this study appear to have no influence on the chance of failure . In rebonded posterior resin-bonded bridges , the bonding system silica-coating/Microfill Pontic C was more retentive than the other systems tested Output:	Moreover , the survival rate was higher for RBBs inserted in the anterior area of the oral cavity compared with posterior RBBs . Despite the high survival rate of RBBs after 5 and 10 years , technical complications like de-bonding and minor chipping were frequent . RBBs with zirconia framework and RBBs with one retainer tooth showed the highest survival rate
MS21874	*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 describe the epidemiology of incomplete abortion ( spontaneous miscarriage and illegally induced ) in South Africa . DESIGN Multicentre , prospect i ve , descriptive study . SETTING Fifty-six public hospitals in nine provinces ( a stratified , r and om sample of all hospitals treating gynaecological emergencies ) . PATIENTS All women of gestation under 22 weeks who presented with incomplete abortion during the 2-week study period . MAIN OUTCOME MEASURES Incidence of , morbidity associated with and mortality from incomplete abortion . MAIN RESULTS An estimated 44686 ( 95 % CI 35633 - 53709 ) women per year were admitted to South Africa 's public hospitals with incomplete abortion . An estimated 425 ( 95 % CI 78 - 735 ) women die in public hospitals from complications of abortion . Fifteen per cent ( 95 % CI 13 - 18 ) of patients have severe morbidity while a further 19 % ( 95 % CI 16 - 22 ) have moderate morbidity , as assessed by categories design ed for the study which largely reflect infection . There were marked inter-provincial differences and inter-age group differences in trimester of presentation and proportion of patients with appreciable morbidity . CONCLUSIONS Incomplete abortions and , in particular , unsafe abortions are an important cause of mortality and morbidity in South Africa . The methods used in this study underestimate the true incidence for reasons that are discussed . A high priority should be given to the prevention of unsafe abortion A r and omised controlled trial involving 140 non-septic incomplete abortions was performed to determine the efficacy of prophylactic tetracycline as practice d in these cases in Harare Central Hospital . The treatment group ( 62 ) received tetracycline ( 500 mg four times daily ) for a week . The remainder acted as controls . No significant difference in sepsis rate between treatment and control groups was noted . The high sepsis recorded in the treatment group was thought to be due to poor compliance . A new prophylaxis regimen has been suggested In a double‐blind controlled trial the effect of prophylactic metronidazole on postabortal infection in women with a history of pelvic inflammatory disease ( PID ) was assessed . One hundred and thirty‐five women were eligible for r and omization , of whom 17 were excluded . The regimen consisted of oral metronidazole 400 mg 1 h before the abortion and again 4 and 8 h after , or else placebo . In the placebo group the rate of postabortal PID was 13.0 % ( 7/54 ) and in the metronidazole group 10.9 % ( 7/64 ) , a nonsignificant difference ( p>0.7 ) . Women in gestational weeks 11−12 had a significantly increased rate of postabortal PID compared with women in weeks 6–10 ( p<0.005 ) , but this rate was not influenced by the treatment ( p>0.2 ) . Women with parity 1 had a significantly increased rate of postabortal PID compared with women with parity 0 ( p<0.05 ) , but again the treatment did not influence this rate significantly ( p>0.2 ) . The number of hospital days for women in the metronidazole group did not differ significantly from that in the placebo group ( p<0.1 ) . The amount of metronidazole administered for prophylactic and postabortal treatment was significantly greater in the metronidazole group ( p<0.001 ) . The amounts of other antibiotics prescribed showed non‐significant differences between the two groups ( all p‐values > 0.3 ) This r and omised controlled trial of 357 patients who had had an incomplete abortion compared suction curettage with conventional curettage for evacuation of the uterus . The 179 patients undergoing suction curettage had a significantly lower intra-operative blood loss ( P < 0.0001 ) and a significantly higher mean haemoglobin level at follow-up compared with the 178 patients who had conventional curettage . Suction curettage was a faster procedure and less painful . No difference was found between the two groups with regard to the incidence of post-abortal sepsis , or the re-evacuation rate . No problems were encountered with the use of suction curettage in the presence of uterine sepsis . In an era where blood transfusions should be kept to an absolute minimum , suction curettage will help to save blood in several ways In 1994 , a national hospital-based study was undertaken of cases of incomplete abortion presenting to public hospitals in South Africa . Data were collected for all women admitted to a r and om sample of hospitals with incomplete abortion during a two-week period . The WHO protocol for such studies was used as a basis for developing the methods to describe the epidemiology of incomplete abortion and hospital management of cases . Attempts were made to estimate the proportion of cases that might have been induced . This report focuses on method ological issues arising from the study that have implication s for future research . The findings demonstrate that only a small proportion of the women acknowledged having had an induced abortion and that only a few of those who did showed evidence of interference with pregnancy . Clinical opinion of sepsis and the likelihood of induction were found to be highly unreliable . These findings considerably reduce the usefulness of the WHO- protocol method of estimating the likely origin of incomplete abortions . Results presented in terms of three partially overlapping descriptive categories are judged to better reflect the limitations of the data collected The responses to therapy with either clindamycin alone or penicillin plus chloramphenicol in 77 patients with septic abortions were compared in a r and omized , double-blind study . Although fever index and duration of hospitalization were similar for both groups of patients , significantly more patients in the group that received clindamycin developed major complications ( P less than 0.05 ) . This is believed to result from clindamycin 's lack of activity against aerobic gram-negative bacilli . Aggressive management that included early uterine evacuation and broad-spectrum antibiotics effective against both aerobic and anaerobic bacteria was the key to reduced morbidity and mortality rates in treatment of septic abortion . For patients treated with clindamycin , early uterine evacuation appeared more important than antibiotic therapy ( P less than 0.005 ) . Bacteremia was documented in a total of 29 patients ( 38 % ) . Bacteremia was polymicrobial in eight patients ( 28 % ) and involved anaerobes exclusively in 18 ( 62 % ) , aerobes exclusively in nine ( 31 % ) , and both aerobes and anaerobes in two ( 7 % ) . The organisms most frequently isolated were Bacteroides ( other than Bacteroides fragilis ) , Peptostreptococcus , and Escherichia coli Opinion is divided as to the advisability of routine use of prophylactic antibiotics for curettage abortion . Six studies , including three r and omized clinical trials , suggest that prophylaxis reduces infectious morbidity associated with curettage abortions by about one half . Three other studies , two involving prophylaxis for instillation abortions and one involving a vaginal antiseptic for curettage abortion , support the hypothesis that antimicrobial prophylaxis reduces morbidity . Tetracyclines are commonly used for this purpose . The cost of routine prophylaxis even with an expensive tetracycline would appear to be offset by the savings in direct and indirect costs . Prophylaxis may help prevent both short-term morbidity and potential late sequelae , such as ectopic pregnancy and infertility Objective To determine the prevalence of bacterial vaginosis in women undergoing first trimester suction termination of pregnancy and to evaluate the efficacy of metronidazole in reducing the risk of post abortal pelvic infection in women with bacterial vaginosis OBJECTIVE To estimate prospect ively whether reducing oral doxycycline prophylaxis from 7 to 3 days increases the incidence of endometritis after elective first-trimester vacuum abortion . METHODS We r and omized 800 women requesting first-trimester abortion to two study groups : 1 ) 100 mg of doxycycline administered orally twice a day for 7 days or 2 ) 100 mg of doxycycline orally twice a day for 3 days followed by an oral placebo twice daily for the last 4 days . Doxycycline was prescribed immediately after surgery . RESULTS There were no statistically significant differences in age , race , gravidity , parity , number of previous abortions , current gestational age , and history of previous pelvic infection , chlamydia , or intrauterine device use . Women in the doxycycline plus placebo group were more likely to have had a history of gonorrhea ( 3.3 % versus 0.8 % , P = .42 ) or chlamydia ( 7.0 % versus 4.3 % , P = .18 ) . The 66.3 % of enrollees returning for 2-week examinations were distributed similarly between study groups and were similarly compliant in self-reported pill taking ( mean 97.5 % ) . The study groups did not differ in the incidence of postoperative symptoms or examination findings suggesting infection . One patient in the doxycycline-only group developed endometritis and was treated as an outpatient . CONCLUSION Shortening oral doxycycline prophylaxis from 7 to 3 days had no adverse effect on the incidence of postabortion infection Objective To investigate the incidence of post‐operative infection after first trimester abortion in women treated with a long‐acting cephalosporin ( ceftriaxone ) compared with low risk patients receiving no treatment and with high risk patients receiving our st and ard treatment of ampicillin/pivampicillin and metronidazole complications . Three patients had haemoptysis and two slight epistaxis . Three patients vomited , including the one in whom the procedure was ab and oned . There were 39 visible tumours . In 29 out of the 38 of these that were examined the histological opinion was definitive . Failure to make a positive diagnosis was associated with necrotic tumour tissue , previous radiotherapy , or a difficult biopsy . Where the appearance was of extrinsic compression a positive diagnosis was possible in only two out of 11 cases . In 11 cases examination showed non-malignant disease The efficacy of prophylactic antibiotic therapy in induced first-trimester abortions was investigated in a double-blind study . Of the 493 women in the study , 254 received doses of 2 million IU of penicillin G intramuscularly one-half hour before and 3 hours after the procedure , followed by 350 mg of pivampicillin three times daily for 4 days , and 239 women received corresponding doses of placebo . The incidence of pelvic infectious complications was 5.5 % in the treated group and 10.9 % in the control group ( p = 0.05 ) . The difference could be attributed to a selective prophylactic effect in women who had earlier suffered from pelvic inflammatory disease ( N = 105 ) . The rate of infection in this group was 22.4 % among those receiving placebo and 2.1 % among those receiving antibiotics ( p = 0.006 ) . Prophylactic administration of antibiotics for first-trimester abortions should be used in women who have earlier had pelvic inflammatory disease A prospect i ve double-blind study was performed to evaluate the effect of prophylactic antibiotic treatment before induced abortion . Eight hundred consecutive women admitted for first-trimester abortion , without signs of genital infection or antibiotic use in the last three weeks , were included in the study . Doxycycline 400 mg or placebo was given as a single oral dose ten to 12 hours before vacuum aspiration . Ninety-one women ( 11.8 % ) returned to the hospital with suspected complications . Thirty-two of these women were diagnosed as having pelvic inflammatory disease , eight of whom ( 2.1 % ) had received doxycycline before the abortion and 24 of whom ( 6.2 % ) had received placebo , a statistically significant difference ( P < .01 ) . A history of pelvic inflammatory disease increased the risk of developing it again after an abortion Objective To evaluate the efficacy of metronidazole to reduce post‐abortion complications among women with bacterial vaginosis Objective To evaluate the effectiveness and efficiency of a tailored multifaceted strategy , delivered by a national clinical effectiveness programme , to implement a guideline on induced abortion The prophylactic use of 300 mg doxycycline at the time of an abortion was evaluated in a r and omized controlled trial . In the group with negative chlamydia screening results , only two ( 0.4 % ) of 502 patients who received prophylactic treatment developed pelvic infection , compared with 15 ( 3.0 % ) of 497 patients who received placebos ( p = 0.001 ) . The same effectiveness was found in women with positive chlamydia screening results . Vomiting was the major side effect of the medication and could limit its use . A simulation of selective prophylaxis in women with negative chlamydia screening results showed that its selective use in patients with a history of gonorrhea or in nulliparous women with multiple sex partners could be nearly two thirds as effective as general prophylaxis A r and omized prospect i ve double-blind study was conducted to determine the efficacy of prophylactic antibiotics as compared with placebo in 198 women undergoing secondtrimester intraamniotic injection abortions . Patients received either sodium cephalothin or placebo intravenously before Output:	No differences were detected in postabortal infection rates with routine prophylaxis or control . However , compliance with antibiotic treatment was also low . There is not enough evidence to evaluate a policy of routine antibiotic prophylaxis to women with incomplete abortion
MS21875	*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 Forty-five patients with a primary diagnosis of muscular MD were evaluated and treated in a university based facial pain center . The patients were equally and r and omly assigned to one of three treatment groups . Group 1 patients were treated with traditional therapies appropriate for the particular patient . Group two patients used similar therapies that were appropriate for the patient but also had an oral vertical exercise device integrated into their therapy . Patients in the third group were instructed in home care , educated about TMD , and instructed in the use of the oral exercise device . Results indicated that all three groups demonstrated significant overall patient clinical and subjective improvement . The three groups did not differ significantly from each other in degree of patient improvement A study of the effectiveness of physical therapy for patients with myofacial pain dysfunction syndrome was performed . Clinical evaluation of 120 patients revealed marked male preponderance , distribution according to age showed a great prevalence of the third decade , and most common chief complaints were pain and muscle tenderness . Patients were classified r and omly into three equal groups treated by muscle relaxant drugs , shortwave diathermy , and ultrasonic therapy , respectively . Regular follow-up was carried out for 6 to 12 months to assess patients ' responses to different forms of treatment . Evaluation revealed marked relief of symptoms by the use of physical therapy , and the best results were obtained by the use of ultrasonic therapy Objective The aim of the present study was to evaluate the effects of upper thoracic manipulation on pain in subjects with temporom and ibular disorder . Design Thirty-two women with a diagnosis of temporom and ibular disorder were r and omly allocated to an experimental group ( n = 16 ) , su bmi tted to upper thoracic manipulation , and a placebo group ( n = 16 ) , su bmi tted to a procedure in the thoracic region with no therapeutic effect . All volunteers underwent an evaluation of pain in the masticatory muscles and the temporom and ibular joint using an algometer and the visual analog scale before and immediately after the procedure as well as after 48–72 hrs . Two-way repeated- measures analysis of variance was used for the intragroup and intergroup analyses , with the level of significance set to 5 % ( P < 0.05 ) . Cohen d was calculated for the determination of the effect size . Results No significant group-by-time interaction was found ( P > 0.05 ) for algometry in any analysis , and Cohen d revealed no significant effect of the treatment . Moreover , no significant group-by-time interaction was found for facial pain intensity determined using the visual analog scale ( P > 0.05 ) , and Cohen d also revealed no significant effect of the treatment regarding this variable . Conclusions On the basis of the present findings , upper thoracic spinal manipulation does not lead to a reduction in pain in women with temporom and ibular disorder BACKGROUND Temporom and ibular pain has multiple etiologies and a range of therapeutic options . In this pilot study , the authors assessed the feasibility of conducting a larger trial to evaluate chiropractic treatment of temporom and ibular disorders ( TMDs ) . METHODS The authors assigned 80 participants r and omly into one of the following four groups , all of which included a comprehensive self-care program : reversible interocclusal splint therapy ( RIST ) , Activator Method Chiropractic Technique ( AMCT ) ( Activator Methods International , Phoenix ) , sham AMCT and self-care only . They made assessment s at baseline and at month 2 and month 6 , including use of the Research Diagnostic Criteria for Temporom and ibular Disorders . RESULTS The authors screened 721 potential participants and enrolled 80 people ; 52 participants completed the six-month assessment . The adjusted mean change in current pain over six months , as assessed on the 11-point numerical rating scale , was 2.0 ( 95 percent confidence interval , 1.1 - 3.0 ) for RIST , 1.7 ( 0.9 - 2.5 ) for self-care only , 1.5 ( 0.7 - 2.4 ) for AMCT and 1.6 ( 0.7 - 2.5 ) for sham AMCT . The authors also assessed bothersomeness and functionality . CONCLUSIONS The authors found the study design and methodology to be manageable . They gained substantial knowledge to aid in conducting a larger study . AMCT , RIST and self-care should be evaluated in a future comparative effectiveness study . PRACTICAL IMPLICATION S This pilot study was a necessary step to prepare for a larger study that will provide clinicians with information that should be helpful when discussing treatment options for patients with TMD Background Myogenous temporom and ibular disorders ( TMD ) are considered to be a common musculoskeletal condition . No studies exist comparing intra-oral myofascial therapies to education , self-care and exercise ( ESC ) for TMD . This study evaluated short-term differences in pain and mouth opening range between intra-oral myofascial therapy ( IMT ) and an ESC program . Methods Forty-six participants with chronic myogenous TMD ( as assessed according to the Research Diagnostic Criteria Axis 1 procedure ) were consecutively block r and omised into either an IMT group or an ESC group . Each group received two sessions per week ( for five weeks ) of either IMT or short talks on the anatomy , physiology and biomechanics of the jaw plus instruction and supervision of self-care exercises . The sessions were conducted at the first author ’s jaw pain and chiropractic clinic in Sydney , Australia . Primary outcome measures included pain at rest , upon opening and clenching , using an eleven point ordinal self reported pain scale . A secondary outcome measure consisted of maximum voluntary opening range in millimetres . Data were analysed using linear models for means and logistic regression for responder analysis . Results After adjusting for baseline , the IMT group had significantly lower average pain for all primary outcomes at 6 weeks compared to the ESC group ( p < 0.001 ) . These differences were not clinical ly significant but the IMT group had significantly higher odds of a clinical ly significant change ( p < 0.045 ) . There was no significant difference in opening range between the IMT and ESC groups . Both groups achieved statistically significant decreases in all three pain measures at six weeks ( p ≤ 0.05 ) , but only the IMT group achieved clinical ly significant changes of 2 or more points . Conclusion This study showed evidence of superiority of IMT compared to ESC over the short-term but not at clinical ly significant levels . Positive changes over time for both IMT and ESC protocol s were noted . A longer term , multi-centre study is warranted . Trial registration Australian and New Zeal and Clinical Trials Registry ACTRN12610000508077 A r and om sample of U.S. dentists was surveyed with a mailed question naire to determine the number of splints that they fabricated over the preceding year for bruxers , patients with myofascial pain-dysfunction syndrome and patients with TM joint pain . The results indicate that a significant number of dentists treat these disorders with dental splints . Estimates are provided for the dental profession 's yearly splint output for each disorder Abstract The aim of this research was to study if changes in condyle position in temporom and ibular disorders ( TMD ) patients could be a factor that is affected by resilient appliance therapy and if it influences the treatment outcome . The study investigated 48 patients r and omly assigned to a treatment group ( T group = 21 patients , using resilient appliance ) or a control group ( C group = 27 patients , using nonoccluding appliance ) . Changes in the condyle-fossa relationship ( with and without the appliance ) were determined in an MRI examination . Ten weeks after treatment , the treatment outcome was measured . The results showed that with the appliance , change in condyle position occurred in 76 % of the T group and 22 % of the C group ( p<0.001 ) . Sixty-seven percent ( 67 % ) of the T group and 44 % of the C group experienced a successful treatment outcome . Treatment outcome was not related to changes in condyle position in patients with TMD pain OBJECTIVE Studies investigating the efficacy of intraoral myofascial therapies ( IMTs ) for chronic temporom and ibular disorder ( TMD ) are rare . The present study was an expansion of a previously published pilot study that investigated whether chiropractic IMT and the addition of education and self-care were superior to no-treatment or IMT alone for 5 outcome measures -interincisal opening range , jaw pain at rest , jaw pain upon opening , jaw pain upon clenching , and global reporting of change-over the course of 1 year . METHODS Ninety-three participants with myogenous TMD between the ages of 18 and 50 years experiencing chronic jaw pain of longer than 3 months in duration were recruited for the study . Successful applicants were r and omized into 1 of 3 groups : ( 1 ) IMT consisting of 2 treatment interventions per week for 5 weeks , ( 2 ) IMT plus education and " self-care " exercises ( IMTESC ) , and ( 3 ) wait-list control . The main outcome measures were used . Range of motion findings were measured by vernier callipers in millimeters , and pain scores were quantified using an 11-point self-reported grade d chronic pain scale . Global reporting of change was a 7-point self-reported scale , balanced positively and negatively around a zero midpoint . RESULTS There were statistically significant differences in resting , opening and clenching pain , opening scores , and global reporting of change ( P < .05 ) in both treatment groups compared with the controls at 6 months and 1 year . There were also significant differences between the 2 treatment groups at 1 year . CONCLUSIONS The study suggests that both chiropractic IMT and IMTESC were superior to no-treatment of chronic myogenous TMD over the course of 1 year , with IMTESC also being superior to IMT at 1 year AIMS To compare the effectiveness of adding cyclobenzaprine , tizanidine , or placebo to patient education and a self-care management program for patients with myofascial pain and specifically presenting with jaw pain upon awakening . METHODS Forty-five patients with a diagnosis of myofascial pain based on the guidelines of the American Academy of Orofacial Pain participated in this 3-week study . The subjects were r and omly assigned into one of three groups : placebo group , TZA group ( tizanidine 4 mg ) , or CYC group ( cyclobenzaprine 10 mg ) . Patients were evaluated for changes in pain intensity , frequency , and duration by using the modified Severity Symptoms Index and changes in sleep quality with the use of the Pittsburgh Sleep Quality Index . Data were analyzed by ANOVA and post-hoc or nonparametric statistical tests as appropriate . RESULTS All three groups had a reduction in pain symptoms and improvement of sleep quality based on a comparison of pretreatment and treatment scores . However , no significant differences among the groups were observed at the posttreatment evaluation . CONCLUSION The use of tizanidine or cyclobenzaprine in addition to self-care management and patient education was not more effective than placebo for the management of patients with myofascial jaw pain upon awakening Abstract Objective . The aim of this study was to analyze and compare prevalence of signs and frequently occurring symptoms indicative of temporom and ibular disorder ( TMD ) and headaches in 35- , 50- , 65- and 75-year-old men and women in Västerbotten County , Sweden . Material s and methods . From a total target population of 11 324 subjects living in Västerbotten County in the year 2002 , 300 individuals in each age group were r and omly selected . Of these , 998 ( 82 % response rate ) answered and returned a postal question naire and 779 ( 65 % response rate ) individuals accepted a clinical examination . Results . The prevalence of frequent TMD symptoms peaked among 50-year-old women and then declined . Women at this age reported significantly higher prevalence compared to men for all TMD symptoms except temporom and ibular joint locking . In the 65- and 75-year-olds , the prevalence was practically equal between men and women as well as between these ages . Frequent headaches showed the highest prevalence among 35- and 50-year-old women , with a statistically significant difference between men and women of 50 years of age ( p < 0.05 ) . Fifty-year-old women had statistically significantly higher prevalence of muscle pain to palpation ( p < 0.001 ) , temporom and ibular joint sounds ( p < 0.01 ) and impaired maximal jaw opening capacity ( p < 0.01 ) , compared to 50-year-old men . Conclusions . The different symptoms indicative of TMD and headaches showed a similar pattern , with higher prevalence among the 35- and 50-year-old , as compared to the 65- and 75-year-old , participants . The pattern may be related to biological , psychosocial or generation-related factors Summary Dental hygienist‐delivered pain self‐management training was superior to continuous oral contraceptive therapy for women with TMD pain ; focusing on menstrually‐related changes in symptoms did not increase its efficacy . ABSTRACT Mounting evidence supports the importance of hormonal fluctuations in temporom and ibular disorder ( TMD ) pain among women . Stabilizing influential hormones or having a plan and skills for coping with hormonally related increases in TMD pain , therefore , may be beneficial for women with TMD pain . This r and omized clinical trial evaluated the short‐ and long‐term efficacy of 3 interventions for women with TMD pain : ( 1 ) dental hygienist‐delivered pain self‐management training ( SMT ; n = 59 ) ; ( 2 ) the same dental hygienist‐delivered pain self‐management training , but with a focus on menstrual cycle‐related changes in pain and Output:	The general heterogeneity was not found among included trials . But predictive intervals ( PrIs ) were conspicuously wider than confidential intervals ( CIs ) of all pairwise comparisons , indicating that heterogeneity may exist between studies . Complementary therapy showed the greatest probability ( 42.7 % ) to be the best intervention . Based on the limited evidence of available trials , complementary therapy seemed to be slightly more effective than remaining treatment modalities for pain reduction in TMD patients with masticatory muscle pain .
MS21876	*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: Aim To determine the effectiveness and cost-effectiveness of a mobile phone intervention to improve exercise capacity and physical activity behaviour in people with ischaemic heart disease ( IHD ) . Methods and results In this single-blind , parallel , two-arm , r and omized controlled trial adults ( n = 171 ) with IHD were r and omized to receive a mobile phone delivered intervention ( HEART ; n = 85 ) plus usual care , or usual care alone ( n = 86 ) . Adult participants aged 18 years or more , with a diagnosis of IHD , were clinical ly stable as out patients , able to perform exercise , able to underst and and write English , and had access to the Internet . The HEART ( Heart Exercise And Remote Technologies ) intervention involved a personalized , automated package of text messages and a secure website with video messages aim ed at increasing exercise behaviour , delivered over 24 weeks . All participants were able to access usual community-based cardiac rehabilitation , which involves encouragement of physical activity and an offer to join a local cardiac support club . All outcomes were assessed at baseline and 24 weeks and included peak oxygen uptake ( PVO2 ; primary outcome ) , self-reported physical activity , health-related quality of life , self-efficacy and motivation ( secondary outcomes ) . Results showed no differences in PVO2 between the two groups ( difference −0.21 ml kg−1 min−1 , 95 % CI : −1.1 , 0.7 ; p = 0.65 ) at 24 weeks . However significant treatment effects were observed for selected secondary outcomes , including leisure time physical activity ( difference 110.2 min/week , 95 % CI : −0.8 , 221.3 ; p = 0.05 ) and walking ( difference 151.4 min/week , 95 % CI : 27.6 , 275.2 ; p = 0.02 ) . There were also significant improvements in self-efficacy to be active ( difference 6.2 % , 95 % CI : 0.2 , 12.2 ; p = 0.04 ) and the general health domain of the SF36 ( difference 2.1 , 95 % CI : 0.1 , 4.1 ; p = 0.03 ) at 24 weeks . The HEART programme was considered likely to be cost-effective for leisure time activity and walking . Conclusions A mobile phone intervention was not effective at increasing exercise capacity over and above usual care . The intervention was effective and probably cost-effective for increasing physical activity and may have the potential to augment existing cardiac rehabilitation services Background Several heart failure studies have shown promising results for implementing telehealthcare . These studies have led to clinical and political interest in telehealthcare as a way to improve heart failure outcomes and lower costs . However , there is a need for large-scale clinical trials with cost-effectiveness assessment s. Methods / design The present study is known as the TeleCare North Heart Failure Trial in Denmark . We are study ing the health effectiveness and cost-effectiveness of a telehealth ( Telekit ) solution compared with usual care for patients with heart failure . The design is a multicenter , two-arm , parallel-group , nonblinded , superiority r and omized controlled trial . Outpatient healthcare centers will be responsible for recruiting eligible participants ( 600 participants are expected ) for the trial in the geographic area of the North Denmark Region . Participants are qualified for inclusion if they have been diagnosed according to national guidelines and are categorized in New York Heart Association class 2 , 3 , or 4 . Patients must have a permanent residence and be motivated to use telehealth care . The primary outcomes are changes in health-related quality of life ( assessed using the Kansas City Cardiomyopathy Question naire , the EuroQol EQ-5D-5L question naire , and the Short Form Health Survey [ SF-36 ] ) and in the incremental cost-effectiveness ratio measured from baseline to follow-up . The secondary outcomes are changes in mortality and in physiological indicators such as blood pressure , pulse , and weight . Discussion The TeleCare North Heart Failure Trial is intended to improve the international evidence base for the health effectiveness and cost-effectiveness of telehealthcare for patients with heart failure . The expectation is that the results of the trial can be generalized to all municipalities in Denmark and serve as an inspiration for further international research .Trial registration Clinical Trials.gov ( NCT02860013 ) . Registered on 28 July 2016 Aim Although cardiac rehabilitation improves physical fitness after a cardiac event , many eligible patients do not participate in cardiac rehabilitation and the beneficial effects of cardiac rehabilitation are often not maintained over time . Home-based training with telemonitoring guidance could improve participation rates and enhance long-term effectiveness . Methods and results We r and omised 90 low-to-moderate cardiac risk patients entering cardiac rehabilitation to three months of either home-based training with telemonitoring guidance or centre-based training . Although training adherence was similar between groups , satisfaction was higher in the home-based group ( p = 0.02 ) . Physical fitness improved at discharge ( p < 0.01 ) and at one-year follow-up ( p < 0.01 ) in both groups , without differences between groups ( home-based p = 0.31 and centre-based p = 0.87 ) . Physical activity levels did not change during the one-year study period ( centre-based p = 0.38 , home-based p = 0.80 ) . Healthcare costs were statistically non-significantly lower in the home-based group ( € 437 per patient , 95 % confidence interval –562 to 1436 , p = 0.39 ) . From a societal perspective , a statistically non-significant difference of € 3160 per patient in favour of the home-based group was found ( 95 % confidence interval –460 to 6780 , p = 0.09 ) and the probability that it was more cost-effective varied between 97 % and 75 % ( willingness-to-pay of € 0 and € 100,000 per quality -adjusted life-years , respectively ) . Conclusion We found no differences between home-based training with telemonitoring guidance and centre-based training on physical fitness , physical activity level or health-related quality of life . However , home-based training was associated with a higher patient satisfaction and appears to be more cost-effective than centre-based training . We conclude that home-based training with telemonitoring guidance can be used as an alternative to centre-based training for low-to-moderate cardiac risk patients entering cardiac rehabilitation Objectives To compare the costs and cost-effectiveness of managing patients with uncontrolled blood pressure ( BP ) using telemonitoring versus usual care from the perspective of the National Health Service ( NHS ) . Design Within trial post hoc economic evaluation of data from a pragmatic r and omised controlled trial using an intention-to-treat approach . Setting 20 socioeconomically diverse general practice s in Lothian , Scotl and . Participants 401 primary care patients aged 29–95 with uncontrolled daytime ambulatory blood pressure ( ABP ) ( ≥135/85 , but < 210/135 mm Hg ) . Intervention Participants were central ly r and omised to 6 months of a telemonitoring service comprising of self-monitoring of BP transmitted to a secure website for review by the attending nurse/doctor and patient , with optional automated patient decision-support by text/email ( n=200 ) or usual care ( n-201 ) . R and omisation was undertaken with minimisation for age , sex , family practice , use of three or more hypertension drugs and self-monitoring history . Main outcome measures Mean difference in total NHS costs between trial arms and blinded assessment of mean cost per 1 mm Hg systolic BP point reduced . Results Home telemonitoring of BP costs significantly more than usual care ( mean difference per patient £ 115.32 ( 95 % CI £ 83.49 to £ 146.63 ; p<0.001 ) ) . Increased costs were due to telemonitoring service costs , patient training and additional general practitioner and nurse consultations . The mean cost of systolic BP reduction was £ 25.56/mm Hg ( 95 % CI £ 16.06 to £ 46.89 ) per patient . Conclusions Over the 6-month trial period , supported telemonitoring was more effective at reducing BP than usual care but also more expensive . If clinical gains are maintained , these additional costs would be very likely to be compensated for by reductions in the cost of future cardiovascular events . Longer-term modelling of costs and outcomes is required to fully examine the cost-effectiveness implication s. Trial registration International St and ard R and omised Controlled Trials , number IS RCT N72614272 Aims The purpose of this prospect i ve study was to investigate whether internet-based remote monitoring offers a safe , practical , and cost-effective alternative to the in-office follow-up visits of patients with an implantable cardioverter defibrillator ( ICD ) . Methods and results Forty-one patients ( 62 ± 10 years , range 41–76 , 83 % male ) with previously implanted ICD were followed for 9 months . One-hundred and nineteen scheduled and 18 unscheduled data transmissions were performed . There were no device-related adverse events . Over 90 % of the patients found the system easy to use . Physicians reported the system as being ‘ very easy ’ or ‘ easy ’ to use and found the data comparable to traditional device interrogation in 99 % of the cases . They were able to address all unscheduled data transmissions remotely . Compared with the in-office visits , remote monitoring required less time from patients ( 6.9 ± 5.0 vs. 182 ± 148 min , P < 0.001 ) and physicians ( 8.4 ± 4.5 vs. 25.8 ± 17.0 min , P < 0.001 ) to complete the follow-up . Substitution of two routine in-office visits during the study by remote monitoring reduced the overall cost of routine ICD follow-up by 524 € per patient ( 41 % ) . Conclusion Remote monitoring offers a safe , feasible , time-saving , and cost-effective solution to ICD follow-up Objectives To investigate the cost-effectiveness of a telehealth intervention for primary care patients with raised cardiovascular disease ( CVD ) risk . Design A prospect i ve within-trial patient-level economic evaluation conducted alongside a r and omised controlled trial . Setting Patients recruited through primary care , and intervention delivered via telehealth service . Participants Adults with a 10-year CVD risk ≥20 % , as measured by the QRISK2 algorithm , with at least 1 modifiable risk factor . Intervention A series of up to 13 scripted , theory-led telehealth encounters with healthcare advisors , who supported participants to make behaviour change , use online re sources , optimise medication and improve adherence . Participants in the control arm received usual care . Primary and secondary outcome measures Cost-effectiveness measured by net monetary benefit at the end of 12 months of follow-up , calculated from incremental cost and incremental quality -adjusted life years ( QALYs ) . Productivity impacts , participant out-of-pocket expenditure and the clinical outcome were presented in a cost-consequences framework . Results 641 participants were r and omised—325 to receive the telehealth intervention in addition to usual care and 316 to receive only usual care . 18 % of participants had missing data on either costs , utilities or both . Multiple imputation was used for the base case results . The intervention was associated with incremental mean per-patient National Health Service ( NHS ) costs of £ 138 ( 95 % CI 66 to 211 ) and an incremental QALY gain of 0.012 ( 95 % CI −0.001 to 0.026 ) . The incremental cost-effectiveness ratio was £ 10 859 . Net monetary benefit at a cost-effectiveness threshold of £ 20 000 per QALY was £ 116 ( 95 % CI −58 to 291 ) , and the probability that the intervention was cost-effective at this threshold value was 0.77 . Similar results were obtained from a complete case analysis . Conclusions There is evidence to suggest that the Healthlines telehealth intervention was likely to be cost-effective at a threshold of £ 20 000 per QALY . Trial registration number IS RCT N27508731 ; Results . Prospect ively registered 05 July 2012 Background Heart failure patients with implantable defibrillators place a significant burden on health care systems . Remote monitoring allows assessment of device function and heart failure parameters , and may represent a safe , effective , and cost-saving method compared to conventional in-office follow-up . Objective We hypothesized that remote device monitoring represents a cost-effective approach . This paper summarizes the economic evaluation of the Evolution of Management Strategies of Heart Failure Patients With Implantable Defibrillators ( EVOLVO ) study , a multicenter clinical trial aim ed at measuring the benefits of remote monitoring for heart failure patients with implantable defibrillators . Methods Two hundred patients implanted with a wireless transmission – enabled implantable defibrillator were r and omized to receive either remote monitoring or the conventional method of in-person evaluations . Patients were followed for 16 months with a protocol of scheduled in-office and remote follow-ups . The economic evaluation of the intervention was conducted from the perspectives of the health care system and the patient . A cost-utility analysis was performed to measure whether the intervention was cost-effective in terms of cost per quality -adjusted life year ( QALY ) gained . Results Overall , remote monitoring did not show significant annual cost savings for the health care system ( € 1962.78 versus € 2130.01 ; P=.80 ) Output:	According to the results , telemedicine improves the clinical outcomes and results in considerable saving in costs . Utilizing telemedicine concurrent with the usual care for service delivery is more cost-effective .
MS21877	*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: Sub clinical hypothyroidism ( sHT ) affects 5 - 15 % of the general population ; however , the need of lifelong L-T(4 ) therapy is still controversial . As myocardium is a main target of thyroid hormone action , we investigated whether sHT induces cardiovascular alterations . Twenty sHT patients were r and omly assigned to receive placebo or L-T(4 ) therapy and were followed for 1 yr . Twenty sex- and age-matched normal subjects served as controls . Doppler echocardiography and videodensitometric analysis were performed in all subjects . Myocardium textural parameters were obtained as mean gray levels , which were then used to calculate the cyclic variation index ( CVI ; percent systolic/diastolic change in mean gray levels ) . Patients had a significantly higher isovolumic relaxation time ( 3.1 + /- 0.5 vs. 2.6 + /- 0.6 ; P < 0.03 ) , peak A ( 0.77 + /- 0.16 vs. 0.56 + /- 0.13 m/s ; P < 0.01 ) , and preejection/ejection time ( PEP/ET ) ratio ( 0.72 + /- 0.05 vs. 0.57 + /- 0.06 ; P < 0.03 ) and a lower CVI ( P < 0.0001 ) than controls . CVI was inversely related to TSH level ( P < 0.0001 ) and PEP/ET ratio ( P < 0.01 ) . L-T(4)-treated patients showed a significant reduction of the PEP/ET ratio ( P < 0.05 ) , peak A ( P < 0.05 ) , and isovolumic relaxation time ( P < 0.05 ) along with a normalization of CVI . Conversely , no changes were observed in the placebo-treated group . In conclusion , sHT affects both myocardial structure and contractility . These alterations may be reversed by L-T(4 ) therapy Sub clinical hypothyroidism ( sHT ) is associated with dyslipidemia and enhanced cardiovascular risk . We assessed carotid artery intima-media thickness ( IMT , high-resolution ultrasonography ) and lipoprotein profile in 45 sHT patients ( aged 37 + /- 11 yr ) at baseline and after 6 months of r and omized , placebo-controlled L-T(4 ) replacement . In comparison with 32 age- and sex-matched controls , sHT patients had elevated total and low-density lipoprotein ( LDL ) cholesterol and ApoB levels ( P = 0.002 , P = 0.0007 , and P = 0.01 , respectively ) and higher mean-IMT values ( P < 0.0001 ) . In stepwise regression analysis , mean-IMT was positively related ( r(2 ) = 0.71 , P < 0.0001 ) to age , TSH , and LDL cholesterol . L-T(4 ) replacement significantly reduced both total and LDL cholesterol ( P < 0.0001 for both ) and mean-IMT ( by 11 % , P < 0.0001 ) . The decrement in IMT was directly related to the decrements of both total cholesterol and TSH ( P = 0.02 and P = 0.0001 , respectively ) . We conclude that early carotid artery wall alterations are present in sHT patients . Whether such IMT increase is related to an early atherosclerotic involvement of the arterial wall can not be clearly decided on the basis of the present results . However , the fact that L-T(4 ) replacement therapy was able to improve both the atherogenic lipoprotein profile and intima-media thickening suggests that lipid infiltration of arterial wall may represent a major mechanism underlying IMT increase in sub clinical hypothyroidism BACKGROUND Sub clinical hypothyroidism ( SCH ) is postulated to increase stroke risk via atherogenic changes associated with abnormal thyroid function . However , the direct relationship of SCH with subsequent stroke is poorly studied . METHODS In this nested case-cohort study , we prospect ively evaluated the association between any SCH and severity of SCH in relation to incident ischemic stroke risk among postmenopausal women in the Women 's Health Initiative Observational Study . Trained Women 's Health Initiative staff , masked to thyroid status , adjudicated stroke cases . We assessed thyroid function using baseline blood specimens . Women with normal free thyroxine levels and thyrotropin ( TSH ) levels ≥4.69 mU/L were considered to have SCH . Primary analysis included 639 ischemic stroke cases and 2927 r and omly selected subcohort members with an average of seven years of follow-up . RESULTS The multivariable adjusted hazard ratios ( HR ) from weighted Cox models were 1.06 ( 95 % confidence interval [ CI ] : 0.77 , 1.46 ) and 0.99 ( 95 % CI : 0.67 , 1.47 ) for women with any SCH and with mild SCH ( TSH 4.69 to 6.99 mU/L ) , when compared with women with normal thyroid function . The HR for moderate/severe SCH ( TSH ≥7.00 mU/L ) was modestly elevated ( HR : 1.22 ; 95 % CI : 0.73 , 2.05 ) . CONCLUSIONS We found no evidence to suggest an association between SCH and ischemic stroke among healthy postmenopausal women Background Health technology assessment s of surgical interventions frequently require the inclusion of non-r and omised evidence . Literature search strategies employed to identify this evidence often exclude a method ological component because of uncertainty surrounding the use of appropriate search terms . This can result in the retrieval of a large number of irrelevant records . Method ological filters would help to minimise this , making literature search ing more efficient . Methods An objective approach was employed to develop MEDLINE and EMBASE filters , using a reference st and ard derived from screening the results of an electronic literature search that contained only subject-related terms . C and i date terms for MEDLINE ( N = 37 ) and EMBASE ( N = 35 ) were derived from examination of the records of the reference st and ard . The filters were vali date d on two sets of studies that had been included in previous health technology assessment s. Results The final filters were highly sensitive ( MEDLINE 99.5 % , EMBASE 100 % , MEDLINE / EMBASE combined 100 % ) with precision ranging between 16.7 % – 21.1 % , specificity 35.3 % – 43.5 % , and a reduction in retrievals of over 30 % . Against the validation st and ards , the individual filters retrieved 85.2 % – 100 % of records . In combination , however , the MEDLINE and EMBASE filters retrieved 100 % against both validation st and ards with a reduction in retrieved records of 28.4 % and 30.1 % Conclusion The MEDLINE and EMBASE filters were highly sensitive and substantially reduced the number of records retrieved , indicating that they are useful tools for efficient literature search ing CONTEXT Data regarding the association between sub clinical hypothyroidism and cardiovascular disease outcomes are conflicting among large prospect i ve cohort studies . This might reflect differences in participants ' age , sex , thyroid-stimulating hormone ( TSH ) levels , or preexisting cardiovascular disease . OBJECTIVE To assess the risks of coronary heart disease ( CHD ) and total mortality for adults with sub clinical hypothyroidism . DATA SOURCES AND STUDY SELECTION The data bases of MEDLINE and EMBASE ( 1950 to May 31 , 2010 ) were search ed without language restrictions for prospect i ve cohort studies with baseline thyroid function and subsequent CHD events , CHD mortality , and total mortality . The reference lists of retrieved articles also were search ed . DATA EXTRACTION Individual data on 55,287 participants with 542,494 person-years of follow-up between 1972 and 2007 were supplied from 11 prospect i ve cohorts in the United States , Europe , Australia , Brazil , and Japan . The risk of CHD events was examined in 25,977 participants from 7 cohorts with available data . Euthyroidism was defined as a TSH level of 0.50 to 4.49 mIU/L. Sub clinical hypothyroidism was defined as a TSH level of 4.5 to 19.9 mIU/L with normal thyroxine concentrations . RESULTS Among 55,287 adults , 3450 had sub clinical hypothyroidism ( 6.2 % ) and 51,837 had euthyroidism . During follow-up , 9664 participants died ( 2168 of CHD ) , and 4470 participants had CHD events ( among 7 studies ) . The risk of CHD events and CHD mortality increased with higher TSH concentrations . In age- and sex-adjusted analyses , the hazard ratio ( HR ) for CHD events was 1.00 ( 95 % confidence interval [ CI ] , 0.86 - 1.18 ) for a TSH level of 4.5 to 6.9 mIU/L ( 20.3 vs 20.3/1000 person-years for participants with euthyroidism ) , 1.17 ( 95 % CI , 0.96 - 1.43 ) for a TSH level of 7.0 to 9.9 mIU/L ( 23.8/1000 person-years ) , and 1.89 ( 95 % CI , 1.28 - 2.80 ) for a TSH level of 10 to 19.9 mIU/L ( n = 70 events/235 ; 38.4/1000 person-years ; P < .001 for trend ) . The corresponding HRs for CHD mortality were 1.09 ( 95 % CI , 0.91 - 1.30 ; 5.3 vs 4.9/1000 person-years for participants with euthyroidism ) , 1.42 ( 95 % CI , 1.03 - 1.95 ; 6.9/1000 person-years ) , and 1.58 ( 95 % CI , 1.10 - 2.27 , n = 28 deaths/333 ; 7.7/1000 person-years ; P = .005 for trend ) . Total mortality was not increased among participants with sub clinical hypothyroidism . Results were similar after further adjustment for traditional cardiovascular risk factors . Risks did not significantly differ by age , sex , or preexisting cardiovascular disease . CONCLUSIONS Sub clinical hypothyroidism is associated with an increased risk of CHD events and CHD mortality in those with higher TSH levels , particularly in those with a TSH concentration of 10 mIU/L or greater Sub clinical hypothyroidism ( sHT ) is associated with enhanced cardiovascular risk . To test the hypothesis that patients with sHT are characterized by endothelial dysfunction and impaired nitric oxide ( NO ) availability , in 14 patients [ serum cholesterol , 218 + /- 41 mg/dl ( 5.6 + /- 0.9 mM ) ] and 28 euthyroid subjects , subdivided into groups A and B [ serum cholesterol , 170 + /- 19 mg/dl ( 4.4 + /- 0.5 mM ) and 217 + /- 21 mg/dl ( 5.6 + /- 0.5 mM ) , respectively ] , we studied the forearm blood flow ( strain-gauge plethysmography ) response to intrabrachial acetylcholine , an endothelium-dependent vasodilator , at baseline and during infusion of N(G)-monomethyl-L-arginine ( L-NMMA ) , a NO synthase inhibitor . Response to sodium nitroprusside and minimal forearm vascular resistances were also evaluated . In sHT patients , vasodilation to acetylcholine was reduced , compared with group B ( + 358 + /- 29 % vs. + 503 + /- 19 % , P = 0.0003 ) and group A ( 663 + /- 65 % , P = 0.02 vs. group B and P = 0.0002 vs. sHT ) . L-NMMA blunted the vasodilation to acetylcholine in groups A and B ( 49.1 + /- 6.3 % and 42.7 + /- 5.5 % maximal forearm blood flow reduction , respectively , P < 0.0001 vs. acetylcholine ) , whereas it was ineffective in sHT patients ( 12.8 + /- 2.5 % ) . Response to sodium nitroprusside and minimal vascular resistances were similar . In sHT ( n = 9 ) patients , 6 months of euthyroidism by levothyroxine replacement increased acetylcholine-vasodilation and restored L-NMMA inhibition . Patients with sHT are characterized by endothelial dysfunction result ing from a reduction in NO availability , an alteration partially independent of dyslipidemia and reversed by levothyroxine supplementation CONTEXT Sub clinical hypothyroidism ( SCH ) is defined as raised serum TSH levels with circulating thyroid hormones within the reference range . It is uncertain whether treatment of SCH with L-thyroxine improves cardiovasc Output:	Our systematic review provides no evidence supporting an increased risk for stroke associated with sub clinical thyroid dysfunction .
MS21878	*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 Green tea polyphenols ( GTPs ) have significant antioxidant and antiinflammatory activities , and prior short‐term studies suggest that these compounds may improve photoaging skin . OBJECTIVES To evaluate the long‐term effects of oral GTPs on the clinical and histologic characteristics of photoaging skin . MATERIAL S AND METHODS Double‐blind , placebo‐controlled trial of 56 women aged 25 to 75 r and omized to 250 mg GTPs or placebo twice daily for 2 years . A blinded dermatologist scored the appearance of photodamaged facial skin at 0 , 6 , 12 , and 24 months . A blinded dermatopathologist scored the histologic characteristics of sun‐exposed arm skin at 0 and 24 months . RESULTS Clinical assessment of facial skin revealed that the GTP group had significant improvement in overall solar damage at 6 months ( p=.02 ) and significant improvement in erythema and telangiectasias at 12 months ( p=.02 ) . The placebo group did not have significant improvements in these parameters at 6 months or 12 months . There were no statistically significant differences in other photoaging parameters at 6 , 12 , or 24 months in the GTP or placebo groups . Histopathologic analysis of sunexposed arm skin showed no statistically significant difference in photoaging parameters in the GTP group or the placebo group at 24 months . CONCLUSIONS Long‐term supplementation with oral GTPs was not superior to placebo in improving clinical or histologic photoaging parameters after 24 months of use . Funding and material s for this study were provided by Nu Skin , Provo , Utah . Dale Kern is an employee of Nu Skin International Green tea ( GT ) consumption is known to be associated with enhanced cardiovascular and metabolic health . The purpose of this study is to examine the hypothesis that supplementation with GT alters insulin resistance and associated cardiovascular risk factors in obese , hypertensive patients . In a double-blind , placebo-controlled trial , 56 obese , hypertensive subjects were r and omized to receive a daily supplement of 1 capsule that contained either 379 mg of GT extract ( GTE ) or a matching placebo , for 3 months . At baseline and after 3 months of treatment , the anthropometric parameters , blood pressure , plasma lipid levels , glucose levels , creatinine levels , tumor necrosis factor α levels , C-reactive protein levels , total antioxidant status , and insulin levels were assessed . Insulin resistance was evaluated according to the homeostasis model assessment -insulin resistance protocol . After 3 months of supplementation , both systolic and diastolic blood pressures had significantly decreased in the GTE group as compared with the placebo group ( P < .01 ) . Considerable ( P < .01 ) reductions in fasting serum glucose and insulin levels and insulin resistance were observed in the GTE group when compared with the placebo group . Serum tumor necrosis factor α and C-reactive protein were significantly lower , whereas total antioxidant status increased in the GTE group compared with the placebo ( P < .05 ) . Supplementation also contributed to significant ( P < .05 ) decreases in the total and low-density lipoprotein cholesterol and triglycerides , but an increase in high-density lipoprotein cholesterol . In conclusion , daily supplementation with 379 mg of GTE favorably influences blood pressure , insulin resistance , inflammation and oxidative stress , and lipid profile in patients with obesity-related hypertension Epidemiological surveys suggest that a higher intake of tea may be associated with a lower risk of CHD . There is accumulating evidence that postpr and ial lipaemia makes a substantial contribution to the incidence of CHD . Our aim was , therefore , to evaluate the effect of tea catechins ( major ingredients in green tea ) on postpr and ial lipid responses in human subjects after the consumption of test meals . In a r and omized triple-crossover design , nine male subjects with mild or borderline hypertriacylglycerolaemia consumed 10 ( control ) , 224 ( moderate dose ) and 674 mg ( high dose ) of the assigned tea catechins three times each along with a st and ardized light meal consisting of a piece of bread spread with 20 g butter . Plasma lipids were measured in the fasting state and 1 , 2 , 3 , 4 and 6 h after consuming the light meal . Results showed that , compared with the control , moderate and high doses of tea catechins reduced the incremental area under the plasma triacylglycerol curves by 15.1 and 28.7 % , respectively . Next , the rapid elevation of remnant-like particle cholesterol was significantly inhibited by a high dose of tea catechins 2 h after consuming the light meal ( P<0.01 ) . In the range of tea catechin dosages , no significant differences were observed in the postpr and ial responses for plasma total cholesterol or NEFA at any time point . In conclusion , this trial demonstrated that tea catechins attenuated the postpr and ial increase in plasma triacylglycerol levels following a fat load . These results may provide evidence for one of the possible mechanisms involved in lowering the incidence of CVD , and may prove useful in further studies on the beneficial health effects of tea drinking Dietary flavonoid intake has been reported to be inversely associated with the incidence of coronary artery disease . To clarify the possible role of tea flavonoids in the prevention of atherosclerosis , we investigated the effects of tea flavonoids on the susceptibility of low-density lipoprotein ( LDL ) to oxidative modification . In an in vitro study , catechins or theaflavins ( 25 - 400 mumol/L ) were added to plasma and incubated for 3 h at 37 degrees C. Then , the LDL fraction was separated by ultracentrifugation . The oxidizability of LDL was estimated by measuring conjugated diene , thiobarbituric acid-reactive substances ( TBARS ) , and lipid peroxides after cupric sulfate was added . TBARS and lipid peroxides in the supernates were also measured after incubation with macrophages . Catechins significantly ( P < 0.01 by ANOVA ) and dose-dependently prolonged the lag time before initiation of oxidation . Among the catechins , epigallocatechin gallate exerted the most marked effect , prolonging the oxidation lag time more than vitamin E at the same molar concentration . Theaflavins exerted stronger inhibitory effects than catechins . Macrophage-mediated LDL oxidation was also inhibited by adding these tea flavonoids to the plasma sample s. In an in vivo study , 14 healthy volunteers consumed 750 mL black tea/d for 4 wk . After the subjects had consumed tea for 4 wk , the lag time before LDL oxidation was significantly ( P < 0.01 ) prolonged from 54 to 62 min . This minor prolongation occurred despite much lower plasma flavonoids than were used in vitro . No significant change was observed in eight control volunteers . LDL exposed to tea flavonoids in vitro or in vivo reduced oxidizability . We speculate that tea flavonoids may have a role in ameliorating atherosclerosis BACKGROUND Tea has been associated with a reduced risk of cardiovascular disease . One proposed mechanism of this risk reduction involves inhibition of lipoprotein oxidation in vivo by antioxidant polyphenolic compounds derived from tea . However , controlled interventions uniformly failed to show that ingestion of tea can inhibit LDL oxidation ex vivo . The absence of effects in previous studies may be due to the isolation of LDL particles from polyphenolic compounds that are present in the aqueous phase of serum . OBJECTIVE The objective of this study was to examine the acute effects of ingestion of black and green tea on ex vivo Cu(2+)-induced lipoprotein oxidation without prior isolation of lipoproteins from serum . DESIGN The acute effects of 4 hot drinks-green tea and black tea ( each at a dose equivalent to 4 st and ard cups ) , water matched to the teas for caffeine content , and water-were assessed in 20 healthy men by using a Latin-square design . The lag time to lipoprotein diene formation , slope of the propagation phase of the oxidation curve , and area under the oxidation curve were calculated . Urinary concentrations of 4-O-methylgallic acid were used as a marker of uptake and metabolism of polyphenolic compounds from tea . RESULTS Significant increases in urinary 4-O-methylgallic acid for black and green tea ( P < 0 . 0001 ) were observed . Caffeine did not significantly influence lipoprotein oxidation . Compared with the water control , there was a greater lag time for black tea ( 5.4 + /- 2.9 min ; P = 0.05 ) that was of borderline significance and a similar trend for green tea ( 4.4 + /- 2.8 min ; P = 0.17 ) . Slope and area under the oxidation curve were not altered . CONCLUSION Black tea has a mild acute effect on ex vivo lipoprotein oxidation in human serum . 2000;71:-7 Prospect i ve studies suggest that tea may protect against cardiovascular disease . A potential mechanism for such an effect involves inhibition of lipid peroxidation by polyphenolic antioxidants derived from tea . Our objective was to determine whether regular ingestion of tea could inhibit in vivo lipid peroxidation . Two controlled intervention studies assessed the effects of regular ingestion of tea on lipid peroxidation determined by measurement of urinary F(2)-isoprostane excretion . Study 1 : The effects of 1000 mL/d of green tea and black tea were compared with hot water containing caffeine in 13 subjects with elevated blood pressure using a r and omized 3-period ( 7 d each ) crossover design . Study 2 : The effects of 1250 mL/d of black tea were compared with hot water in 22 subjects with mildly raised serum total cholesterol concentrations using a r and omized 2-period ( 4 wk each ) crossover design . F(2)-isoprostane excretion was not altered after regular ingestion of green tea ( 273 + /- 48 pmol/mmol creatinine ) or black tea ( 274 + /- 39 pmol/mmol creatinine ) in comparison with hot water ( 263 + /- 47 pmol/mmol creatinine ; Study 1 ) , or by regular ingestion of black tea ( 334 + /- 71 pmol/mmol creatinine ) in comparison with hot water ( 355 + /- 75 pmol/mmol creatinine ; Study 2 ) . These results do not support the suggestion that polyphenolic antioxidants derived from tea inhibit in vivo lipid peroxidation BACKGROUND Polyphenols can act as acceptors of methyl groups during the metabolism of methionine to homocysteine . This may result in elevations in plasma total homocysteine ( tHcy ) concentrations after ingestion of polyphenol-rich beverages such as tea . OBJECTIVES Our major objective was to determine whether regular , moderate-to-high intakes of black tea alter tHcy concentrations . We also assessed the relation between the degree of O-methylation of tea-derived polyphenols and the change in tHcy with regular ingestion of tea . DESIGN Twenty-two subjects completed a r and omized , controlled crossover study . Subjects consumed 1250 mL black tea/d ( 5 cups each containing 2 g tea leaves in 250 mL boiled water ) and 1250 mL hot water/d for 4 wk each . Fasting tHcy concentrations and 24-h urinary excretion of 4-O-methylgallic acid ( 4OMGA , the major O-methylated metabolite of gallic acid ) were measured at the end of each period . 4OMGA was used as a marker of overall O-methylation of tea-derived polyphenols . RESULTS Black tea did not significantly alter mean ( + /- SEM ) tHcy concentrations ( 9.9 + /- 0.5 and 10.0 + /- 0.5 micro mol/L for the hot water and black tea periods , respectively ) . However , the increased excretion of 4OMGA as a consequence of black tea consumption was positively associated with the change in tHcy from the hot water period to the black tea period ( r = 0.55 , P = 0.008 ) . Subjects in the bottom quartile of increase in 4OMGA excretion had a significant decrease in tHcy ( -0.28 + /- 0.10 micro mol/L ; P = 0.046 ) , and those in the top quartile had a significant increase in tHcy ( 0.78 + /- 0.16 micro mol/L ; P = 0.005 ) . CONCLUSIONS Overall , regular ingestion of black tea did not alter mean tHcy concentrations . However , individual differences in O-methylation of polyphenolic compounds may influence the ultimate effects of black tea on tHcy Despite epidemiological evidence that tea consumption is associated with the reduced risk of coronary heart disease , experimental studies design ed to show that tea affects oxidative stress or blood cholesterol concentration have been unsuccessful . We assessed the effects of black tea consumption on lipid and lipoprotein concentrations in mildly hypercholesterolemic adults . Tea and other beverages were included in a carefully controlled weight-maintaining diet Output:	There are very few long-term studies to date examining green or black tea for the primary prevention of CVD .
MS21879	*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 : There is no single generally accepted clinical definition of frailty . Previously developed tools to assess frailty that have been shown to be predictive of death or need for entry into an institutional facility have not gained acceptance among practising clinicians . We aim ed to develop a tool that would be both predictive and easy to use . Methods : We developed the 7-point Clinical Frailty Scale and applied it and other established tools that measure frailty to 2305 elderly patients who participated in the second stage of the Canadian Study of Health and Aging ( CSHA ) . We followed this cohort prospect ively ; after 5 years , we determined the ability of the Clinical Frailty Scale to predict death or need for institutional care , and correlated the results with those obtained from other established tools . Results : The CSHA Clinical Frailty Scale was highly correlated ( r = 0.80 ) with the Frailty Index . Each 1-category increment of our scale significantly increased the medium-term risks of death ( 21.2 % within about 70 mo , 95 % confidence interval [ CI ] 12.5%–30.6 % ) and entry into an institution ( 23.9 % , 95 % CI 8.8%–41.2 % ) in multivariable models that adjusted for age , sex and education . Analyses of receiver operating characteristic curves showed that our Clinical Frailty Scale performed better than measures of cognition , function or comorbidity in assessing risk for death ( area under the curve 0.77 for 18-month and 0.70 for 70-month mortality ) . Interpretation : Frailty is a valid and clinical ly important construct that is recognizable by physicians . Clinical judgments about frailty can yield useful predictive information Applicants for a newly opened special unit for dementia sufferers were r and omly allocated to full-time care in the unit or placed on a waiting list and offered periodic respite care in the meantime . All applicants were living in the community at the time of r and om assignment . Both groups were followed up for three months to assess the effects on the dementia sufferers and on their family care-givers . Care-givers initially had a high level of psychological symptoms , which was greatly reduced after admission of the dementia sufferer to full-time care . By contrast , the care-givers of the community care group of sufferers continued to have a high level of symptoms . Dementia sufferers continued to deteriorate with both forms of care , with little difference between the two groups . Admission of dementia sufferers to full-time care in a special unit appears to be of great benefit to the psychological health of their care-givers and has no adverse effects on the dementia sufferers themselves A program for elderly persons with cognitive impairment and their caregivers was evaluated for its effectiveness and efficiency with regard to caregiver burden , sense of coherence , satisfaction , and cost to the health-care system . The program consisted of a weekly 2-hour visit and walk by volunteers . During a 9-month period in 1997 , all eligible referrals were r and omly assigned to receive the service immediately ( experimental group ) or be placed on a waiting list to receive it 6 weeks later ( control group ) . Eleven caregivers/recipients formed the experimental group ; 10 caregivers/recipients formed the control group . All completed question naires at r and omization and at 6-week follow-up . Perceived burden decreased by 8 % only for the caregivers in the experimental group ( F = 6.8 , p = .02 ) . They indicated that they appreciated the respite and support and that the care recipient enjoyed the visit/walk . Although this study was short in duration and small in sample size , improvements were noted in perceived caregiver burden and caregivers expressed satisfaction with the program . The program did not result in additional health and social-service expenditures Family units ( N = 541 ) of impaired elderly persons and caregivers were r and omly assigned to a control group or one of five treatment groups eligible for a variety of respite or educational services . After 12 months of service eligibility , caregivers of elderly persons remaining in the community reported lower levels of subjective burden . Services appeared to delay nursing home placement among families with adult child caregivers , but encouraged placement by spouse caregivers This article summarizes the study results and presents an evaluative summary of the implementation of study methods design ed to provide guidance in the degree of confidence with which the results may be accepted and generalized to other situations . Patients who were offered VA-ADHC services in the first phase of this study had significantly higher VA health care costs on average than patients assigned to customary care , with no apparent incremental health benefit to themselves or their care givers . One can have a high level of confidence in these results . The ADHC clinical services were implemented as planned , the r and omized controlled trial was implemented successfully , and such threats to validity as insufficient numbers of patients and differential attrition were not present . Certain subgroups of patients assigned to VA-ADHC had VA costs of care that were not significantly higher than those assigned to customary care , although these results must be interpreted with caution . The findings of the second phase of the study evaluating contract ADHC provide no support for choosing to provide either contract ADHC or VA-ADHC over the other . The nonr and omized design and smaller sample size suggest that inferences from the contract ADHC evaluation should be drawn with more caution than those from the VA-ADHC evaluation OBJECTIVES This study reports the findings of an evaluation of the psychological benefits of use of adult day care by family caregivers assisting a relative with dementia . METHODS The study used a quasi-experimental design in which caregivers in the treatment group used substantial amounts of services , whereas caregivers in a control group did not use day care at any point during the evaluation and only small amounts of other respite services . The evaluation was guided by the stress process model of caregiving which distinguishes between appraisal s of primary stressors and well-being . RESULTS Results after 3 months of day care use showed that the treatment group had significantly lower scores than the control group on two of the three measures of primary appraisal s ( overload and strain ) and two of the three measures of well-being ( depression and anger ) . Findings at one year showed that the treatment group had significantly lower scores on overload and depression than the control group . DISCUSSION These results demonstrate that use of adult day care by caregivers of dementia patients results in lower levels of caregiving-related stress and better psychological well-being when compared to that of controls Collaborative working in care for older people is often seen as a desirable goal . However , there can be problems with this approach . This paper reports on a single blind r and omized controlled trial which was carried out to compare outcomes of rehabilitation in two setting s : a day hospital and social services day centres augmented by visiting therapists . The subjects were 105 older patients . Principal outcome measures were the Barthel Index , Philadelphia Geriatric Centre Morale Scale and the Caregiver Strain Index . Two aspects of the trial are examined here . Firstly , we investigated whether trial patients were more disabled than regular day centre attendees . Levels of health and well being amongst trial patients were compared with those of a r and om sample of 20 regular attendees from both of the participating day centres and an additional voluntary sector day centre . Secondly , key staff from the different setting s were interviewed to assess how well the day centre model had worked in practice . Trial patients were significantly more disabled than regular day centre attendees according to the Barthel Index ( P < 0.001 ) , but this difference was no longer significant after three months of treatment . The day centre model had several problems , principally discharge policy , acceptability , facilities and attitudes of staff and regular attendees . Positive aspects of the day centre model , as well as successful rehabilitation , included shared skills , knowledge and re sources . This paper suggests that collaborative working in day centres requires multi purpose facilities . If health staff maintain a permanent presence , benefits can include improved joint working , easier access to health care and the use of rehabilitative therapy as a preventative strategy . Day care setting s can be analyzed as representing different types of communities . Allowing older users a greater degree of choice in facilities may increase the acceptability of care Objectives : To assess outcomes and satisfaction among frail elderly day care clients and their informal caregivers and the impact of adult day care on the cost of health services . Methods : One-hundred eight elderly participants were r and omly assigned to the experimental group ( immediate admission to an adult day care center ) and 104 participants to the control group ( 3 months on a waiting list ) . Results : Participants ’ and caregivers ’ subjective perceptions of the day center ’s effects were positive . However , using st and ard research instruments , there was no evidence of an effect of day center attendance on the client ’s anxiety , depression , or functional status ; on caregiver burden ; or on the cost of health services . Discussion : It is difficult to demonstrate objective ly the benefits of programs and interventions that are perceived by clients , caregivers , and staff to have positive effects . In future studies , maintenance of high levels of participation should be incorporated as an explicit program goal After a baseline interview of 642 caregivers of aged Alzheimer 's disease victims , half were offered formal respite care . Over 12 months , families with respite care maintained their impaired relative significantly longer in the community ( 22 days ) . Although respite was ineffective for caregiver burden and mental health , satisfaction was very high . Although not a strong intervention , respite care can increase caregivers ' quality of life Output:	For all types of respite , the effects upon caregivers were generally small , with better-controlled studies finding modest benefits only for certain subgroups , although many studies reported high levels of caregiver satisfaction . No reliable evidence was found that respite care delays entry to residential care or adversely affects frail older people . The economic evaluations all assessed day care , which tended to be associated with similar or higher costs than usual care .
MS21880	*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 Most early stage kidney cancers are renal cell carcinomas ( RCCs ) , and most are diagnosed incidentally by imaging as small renal masses ( SRMs ) . Indirect evidence suggests that most small RCCs grow slowly and rarely metastasize . OBJECTIVE To determine the progression and growth rates for newly diagnosed SRMs stratified by needle core biopsy pathology . DESIGN , SETTING , AND PARTICIPANTS A multicenter prospect i ve phase 2 clinical trial of active surveillance of 209 SRMs in 178 elderly and /or infirm patients was conducted from 2004 until 2009 with treatment delayed until progression . INTERVENTION Patients underwent serial imaging and needle core biopsies . MEASUREMENTS We measured rates of change in tumor diameter ( growth measured by imaging ) and progression to ≥ 4 cm , doubling of tumor volume , or metastasis with histology on biopsy . RESULTS AND LIMITATIONS Local progression occurred in 25 patients ( 12 % ) , plus 2 progressed with metastases ( 1.1 % ) . Of the 178 subjects with 209 SRMs , 127 with 151 SRMs had>12 mo of follow-up with two or more images , with a mean follow-up of 28 mo . Their tumor diameters increased by an average of 0.13 cm/yr . Needle core biopsy in 101 SRMs demonstrated that the presence of RCC did not significantly change growth rate . Limitations included no central review of imaging and pathology and a short follow-up . CONCLUSIONS This is the first SRM active surveillance study to correlate growth with histology prospect ively . In the first 2 yr , the rate of local progression to higher stage is low , and metastases are rare . SRMs appear to grow very slowly , even if biopsy proven to be RCC . Many patients with SRMs can therefore be initially managed conservatively with serial imaging , avoiding the morbidity of surgical or ablative treatment PURPOSE To evaluate the feasibility and complications of ultrasound (US)-guided biopsy of small renal masses ( SRMs ) and to determine factors that contribute to nondiagnostic biopsy specimens . MATERIAL S AND METHODS Between June 2004 and May 2011 , 58 consecutive patients underwent US-guided core biopsy of a SRM ( > 1 cm and ≤4 cm ) using an 18-gauge core biopsy device . The diagnostic rate , histologic diagnosis , and complications of US-guided core biopsy were assessed . Mann-Whitney U and Fisher exact tests were used to compare diagnostic and nondiagnostic biopsy specimens . Univariate analysis was performed to determine the predictive factors for nondiagnostic biopsy specimens . RESULTS There were 59 biopsies of SRMs performed , and the diagnostic rate was 81 % ( 48 of 59 ) . The mass size of diagnostic and nondiagnostic biopsy specimens ranged from 1.2 - 3.9 cm ( 2.4 cm±0.7 ) for diagnostic specimens and from 1.1 - 3.5 cm ( 1.9 cm±0.7 ) for nondiagnostic specimens ( P = .024 ) . Of the diagnostic biopsy specimens , 77 % ( 37 of 48 ) were malignant , and 23 % ( 11 of 48 ) were benign . Minor complications developed in 20.3 % ( 12 of 59 ) of biopsies . The lesion size or core number threshold for decreasing diagnostic rate was 2 cm or three cores . A cystic mass , fewer cores ( three or fewer cores ) , an upper pole mass , and a small mass ( ≤2 cm ) significantly predicted a nondiagnostic biopsy specimen ( P = .007-.046 ) . CONCLUSIONS US-guided core biopsy is a feasible and safe procedure for histologic diagnosis of a SRM . However , nondiagnostic rates may increase when a cystic mass is biopsied , a mass is located in an upper pole mass , a mass is 2 cm or less , and three cores or fewer are sample OBJECTIVES To determine the accuracy and clinical utility of fine needle aspiration ( FNA ) of small , solid renal masses . METHODS A total of 25 patients with small ( less than 5.0 cm ) , solid , clinical ly localized renal masses were prospect ively identified and evaluated with computed tomography guided FNA with analysis for presence of malignant cells and determination of nuclear grade . The final pathologic findings were used for comparison in each case . All patients had renal cell carcinoma and were managed with radical or partial nephrectomy ; 3 had low- grade lesions ( Fuhrman 's grade 1/4 ) , 2 had high- grade lesions ( Fuhrman 's grade 4/4 ) , and all other patients had intermediate- grade lesions ( Fuhrman 's grade 2/4 or 3/4 ) on final histopathologic assessment . RESULTS Overall , 10 aspirations yielded diagnostic malignant cells , and 9 were read as rare as rare atypical cells suspicious for malignancy . The remainder were negative ( n = 6 ) . Correlation with final nuclear grade was observed in eight instances and discordance in two instances . Subcapsular hematomas were observed at the time of surgery in 10 patients , but in no instance was the operation adversely affected . CONCLUSIONS The diagnostic yield of FNA of small , solid renal masses appears to be too low to justify the potential morbidity of the procedure Purpose In some cases with uncertain renal tumour lesions , it would be helpful to perform biopsies for the preoperative differential diagnosis . In our study , we evaluated the benefit of multi-colour interphase fluorescence in situ hybridization ( M-FISH ) on fine-needle core biopsies in uncertain renal masses . Methods We prospect ively performed three ultrasound-guided percutaneous biopsies in 25 patients with indeterminate renal masses preoperatively . Histopathology was performed on two remaining cores sample s. M-FISH was performed on one core for chromosomes 1 , 2 , 6 , 9 , 7 , 17 , the loci 3p24pter , and 3p13p14 . After interphase FISH evaluation , we classified tumours and compared the results with histopathological findings . Results 16 were classified as renal malignancies : 14 ( 56 % ) clear cell renal cell carcinomas ( RCCs ) , 1 papillary RCCs ( 4 % ) , and 1 “ adenocarcinoma ” ( 4 % ) . Seven patients ( 28 % ) had a benign tumour , i.e. 6 ( 24 % ) were oncocytomas and 1 was classified as leiomyoma ( 4 % ) . In two cases ( 8 % ) , no renal neoplasms were found . In 19 out of 21 cases ( 90.5 % ) , the preoperative diagnostic fine-needle biopsy matched the final histological findings . The combination of histopathological examination and M-FISH leads to a higher ( 95.5 vs. 90.5 % ) diagnostic fidelity as histology alone . Conclusions Ultrasound-guided percutaneous renal tumour biopsy is an accurate and safety method for the histopathologic evaluation of uncertain renal masses . The M-FISH represents a new highly sensitive and specific method to confirm histopathological classification in less than 24 h which can be used in routine laboratory diagnosis OBJECTIVES We evaluated the reliability of sonographic criteria in selecting solid renal masses for percutaneous fine-needle biopsy . METHODS In study 1 ( intraoperative ultrasound study ) , we prospect ively examined 100 consecutive patients scheduled for partial/radical nephrectomy by using two different high-resolution probes ( Philips HDI 5000 , CT8 - 4 , L12 - 5 ; 4 - 12MHz ) . The main tumor was intraoperatively evaluated by B-mode and power Doppler sonography . Morphologic characteristics seen on ultrasound were categorized in (non-)homogenous and (non-)cystic renal masses and were related to findings of pathological examination . Study 1 provided the selection criteria for study 2 . In study 2 ( percutaneous biopsy study ) , under local anesthesia and with the use of an 18-G needle , we prospect ively performed two to three sonographically guided percutaneous biopsies in 30 consecutive patients whose tumors appeared to be homogenous and noncystic according to the sonograph ( convex array 3.5MHz , HDI 5000 , C5 - 2 and Falcon 2101 EXL , B+K Medical ) . RESULTS In the ultrasound study , only 16 ( 22.9 % ) of the 76 clear-cell carcinomas but all 9 ( 100 % ) oncocytoma appeared homogenous and noncystic on high-resolution intraoperative ultrasound . By applying these results to 30 patients of study 2 ( 18 men , 12 women ; aged 63+/-7.7 yr , tumor size 29+/-11.3 mm ) who met these sonographic criteria on preoperative transabdominal ultrasound , we bioptically diagnosed 8 ( 26.7 % ) benign tumors ; 25 of 30 ( 83.3 % ) patients were accurately diagnosed . Small tumors ( <3 cm ) , decreased breathing compliance , and medially located renal lesions seem to negatively influence biopsy results . CONCLUSIONS Kidney tumors that appear noncystic and homogenous on preoperative ultrasound are more likely to be of benign origin . Ultrasound-guided percutaneous biopsy of these solid renal masses could determine renal tumor patients for whom surveillance might be an option . However , experienced and dedicated histopathologic evaluation remains crucial to observe patients with clearly benign biopsy results . All even slightly question able biopsy findings require surgical exploration OBJECTIVE Modern imaging modalities increase the detection of small ( < or=4 cm ) renal tumors , of which about 20 % are benign . As a result , minimal invasive treatments , such as radiofrequency ablation and cryotherapy , and surveillance strategies are gaining popularity . Information that would be helpful when choosing the most appropriate management strategy for this patient group could be obtained from pretherapeutic image-guided biopsy . METHODS Under computed tomography (CT)-fluoroscopic guidance 78 patients with solid renal tumors prospect ively underwent 18-gauge core biopsy . In addition , using the same sheath , fine-needle aspiration was taken in 44 patients and analyzed cytologically . The renal masses were subsequently removed surgically and evaluated histologically . RESULTS Mean patient age was 63+/-13.5 yr ; mean tumor size was 4+/-1.8 cm . The sensitivity of core biopsy and fine-needle aspiration for the detection of renal cell carcinoma ( RCC ) was 93.5 % and 90.6 % , respectively ; Fuhrman grade was correctly predicted in 76 % and 28 % and the correct histologic subtype was identified 91 % and 86 % , respectively . Cytology from fine-needle aspiration revealed a sensitivity in detecting malignant and benign lesions of 100 % and 75 % , respectively . Two of the renal tumors diagnosed as oncocytomas on core biopsy were hybrid tumors with scattered areas of oncocytomas and chromophobe RCC . Complications of CT-guided biopsy included one marginal pneumothorax , which resolved under conservative management , and four small perirenal hematomas detected at follow-up ultrasonography not requiring further therapy . CONCLUSION CT-guided percutaneous preoperative renal tumor biopsy had a high diagnostic accuracy , particularly in predicting malignancy BACKGROUND Percutaneous needle core biopsy has become established in the management of small renal masses ≤ 4 cm ( SRMs ) . Recent series have reported success rates of ≥ 80 % . Nondiagnostic results continue to be problematic . OBJECTIVE To determine the results of SRM biopsy and the outcomes of nondiagnostic biopsy and repeat biopsy . DESIGN , SETTING , AND PARTICIPANTS Patients undergoing renal tumor biopsy ( RTB ) for suspected renal cell carcinoma ( RCC ) were included in a prospect ively maintained data base . MEASUREMENTS The data base was analyzed retrospectively to determine the pathology and outcomes of SRM biopsy . Outcomes of patients with nondiagnostic biopsy were determined . Patients undergoing repeat biopsy were identified and their outcomes analyzed . RESULTS AND LIMITATIONS Three hundred forty-five biopsies were performed ( mean diameter : 2.5 cm ) . Biopsy was diagnostic in 278 cases ( 80.6 % ) and nondiagnostic in 67 cases ( 19.4 % ) . Among diagnostic biopsies , 221 ( 79.4 % ) were malignant , 94.1 % of which were RCC . Histologic subtyping and grading of RCC was possible in 88.0 % and 63.5 % of cases , respectively . Repeat biopsy was performed in 12 of the 67 nondiagnostic cases , and a diagnosis was possible in 10 ( 83.3 % ) . Eight lesions were malignant and two were oncocytic neoplasms . Pathology was available for 15 masses after initial nondiagnostic biopsy ; 11 ( 73 % ) were malignant . Larger tumor size and a solid nature on imaging predicted Output:	CONCLUSIONS RTB is safe and has a high diagnostic yield in experienced centres . Both CB and FNA have good accuracy for the diagnosis of malignancy and histologic subtype , with better performance for CB . The accuracy for Fuhrman grade is fair . The results suggest that RTB has good accuracy in diagnosing renal cancer and its subtypes , and it appears to be safe .
MS21881	*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 was to investigate whether the fascia suture technique ( FST ) can reduce access closure time and procedural costs compared with the Prostar technique ( Prostar ) in patients undergoing endovascular aortic repair and to evaluate the short- and mid-term outcomes of both techniques . METHODS In this two center trial , 100 patients were r and omized to access closure by either FST or Prostar between June 2006 and December 2009 . The primary endpoint was access closure time . Secondary outcome measures included access related costs and evaluation of the short- and mid-term complications . Evaluation was performed peri- and post-operatively , at discharge , at 30 days and at 6 months follow up . RESULTS The median access closure time was 12.4 minutes for FST and 19.9 minutes for Prostar ( p < .001 ) . Prostar required a 54 % greater procedure time than FST , mean ratio 1.54 ( 95 % CI 1.25 - 1.90 , p < .001 ) according to regression analysis . Adjusted for operator experience the mean ratio was 1.30 ( 95 % CI 1.09 - 1.55 , p = .005 ) and for patient body mass index 1.59 ( 95 % CI 1.28 - 1.96 , p < .001 ) . The technical failure rate for operators at proficiency level was 5 % ( 2/40 ) compared with 28 % ( 17/59 ) for those at the basic level ( p = .003 ) . The proficiency level group had a technical failure rate of 4 % ( 1/26 ) for FST and 7 % ( 1/14 ) for Prostar , p = 1.00 , while corresponding rates for the basic level group were 27 % ( 6/22 ) for FST and 30 % ( 11/37 ) for Prostar ( p = .84 ) . There was a significant difference in cost in favor of FST , with a median difference of € 800 ( 95 % CI 710 - 927 , p < .001 ) . CONCLUSIONS In aortic endovascular repair FST is a faster and cheaper technique than the Prostar technique OBJECTIVE The first multicenter r and omized controlled trial was design ed and conducted to assess the safety and effectiveness of totally percutaneous endovascular aortic aneurysm repair ( PEVAR ) with use of a 21F endovascular stent graft system and either an 8 F or 10 F suture-mediated closure system ( the PEVAR trial , NCT01070069 ) . A noninferiority trial design was chosen to compare percutaneous access with st and ard open femoral exposure . METHODS Between 2010 and 2012 , 20 U.S. institutions participated in a prospect i ve , Food and Drug Administration-approved r and omized trial to evaluate percutaneous femoral artery access and closure by a " preclose " technique in conjunction with endovascular abdominal aortic aneurysm repair . A total of 151 patients were allocated by a 2:1 design to percutaneous access/closure ( n = 101 ) or open femoral exposure ( n = 50 [ FE ] ) . PEVAR procedures were performed with either the 8 F Perclose ProGlide ( n = 50 [ PG ] ) or the 10 F Prostar XL ( n = 51 [ PS ] ) closure devices . All endovascular abdominal aortic aneurysm repair procedures were performed with the Endologix 21 F profile ( outer diameter ) sheath-based system . Patients were screened by computed tomography with three-dimensional reconstruction and independent physician review for anatomic suitability and adequate femoral artery anatomy for percutaneous access . The primary trial end point ( treatment success ) was defined as procedural technical success and absence of major adverse events and vascular complications at 30 days . An independent access closure sub study evaluated major access-related complications . Clinical utility and procedural outcomes , ankle-brachial index , blood laboratory analyses , and quality of life were also evaluated with continuing follow-up to 6 months . RESULTS Baseline characteristics were similar among groups . Procedural technical success was 94 % ( PG ) , 88 % ( PS ) , and 98 % ( FE ) . One-month primary treatment success was 88 % ( PG ) , 78 % ( PS ) , and 78 % ( FE ) , demonstrating noninferiority vs FE for PG ( P = .004 ) but not for PS ( P = .102 ) . Failure rates in the access closure sub study analyses demonstrated noninferiority of PG ( 6 % ; P = .005 ) , but not of PS ( 12 % ; P = .100 ) , vs FE ( 10 % ) . Compared with FE , PG and PS yielded significantly shorter times to hemostasis and procedure completion and favorable trends in blood loss , groin pain , and overall quality of life . Initial noninferiority test results persist to 6 months , and no aneurysm rupture , conversion to open repair , device migration , or stent graft occlusion occurred . CONCLUSIONS Among trained operators , PEVAR with an adjunctive preclose technique using the ProGlide closure device is safe and effective , with minimal access-related complications , and it is noninferior to st and ard open femoral exposure . Training , experience , and careful application of the preclose technique are of paramount importance in ensuring successful , sustainable outcomes Introduction While endovascular aortic aneurysm repair ( EVAR ) has significantly reduced the morbidity associated with open surgery , efforts continue to minimise the surgical insult to the patient . We report our experience of percutaneous EVAR . Patients and methods Since June 2005 , 17/20 EVARs ( 85 % ) have been attempted percutaneously by deployment of two Perclose © devices into each femoral artery prior to passage of the device sheath . The sutures are left untied until the sheath is removed at the end of the procedure , when haemostasis is obtained . Patients were entered onto a prospect ively maintained data base and followed up at regular intervals in a dedicated EVAR clinic . Results Access and subsequent graft deployment was successful in all the 17 cases . The range of defects closed ranged from 12–24 Fr . Five patients ( 29 % ) required open groin exploration at the end of the procedure to achieve haemostasis . There was a significantly lower incidence of wound complications in the percutaneous EVAR group ( 6 vs. 10 % open cutdown cases , P < 0.05 , Mann – Whitney U test ) . Conclusion Percutaneous EVAR is both a feasible and safe method of performing endovascular abdominal aortic aneurysm repair , which is associated with a reduction in wound complication rates PURPOSE To evaluate safety and cost benefits of the percutaneous technique for treatment of aortic aneurysm , a prospect i ve r and omized study was performed that compared the endovascular suture technique with conventional cutdown access and repair . MATERIAL S AND METHODS From January 2002 through July 2002 , 30 endografts , including 14 Talent stent-grafts ( Medtronic , Sunrise , Fla ) and 16 Zenith endografts ( Cook , Bloomington , Ind ) were implanted in 30 patients for endovascular aneurysm treatment . The patients were r and omized to either percutaneous technique ( group A ) or conventional cutdown ( group B ) . Fifty-five femoral arteries were cannulated with large-bore ( 14F-25F ) introducers and were included in the study . Safety and efficiency of both techniques were assessed by recording the complication rates , operation time , discharge , and time to ambulation . Comparison of selected estimated costs included both variable and fixed costs for femoral access and expenses for treatment of complications . RESULTS No operative deaths occurred . The complication rates were similar and included 1 arterial thrombosis in each group , 3 lymphoceles in group B , and 1 conversion to cutdown because of bleeding in group A. Mean surgery time ( 86.7 + /- 27 minutes vs 107.8 + /- 38.5 minutes ; P < .05 ) and time to ambulation ( 20.1 + /- 4.3 hours vs 33.1 + /- 18.4 hours ; P < .001 ) were significantly shorter in the group treated percutaneously . Because of the cost of the closure device , total cost of the percutaneous technique averaged 99.2 euro ; more than cutdown . CONCLUSIONS The percutaneous technique decreases the invasiveness of endovascular therapy of aortic aneurysm and reduces operative time and time to ambulation . Complications were roughly equivalent in severity . The additional cost for the device appears to justify its use for this form of aneurysm treatment PURPOSE This study was design ed to describe and evaluate our preliminary results with a percutaneous arterial closure device as compared to those obtained with conventional femoral surgical cut down during endovascular repair of abdominal aortic aneurysms ( AAA ) . MATERIAL AND METHODS Between January 2004 and December 2006 , 40 of 86 AAA patients selected for endovascular repair met the criteria for inclusion in this study . Nineteen of these patients ( Group A ) received a bifurcated endograft placed by direct puncture of the femoral arteries ( 38 femoral triangles ) with closure by a Prostar((R ) ) percutaneous arterial closure device ( Abbott ) . The other 21 patients ( control group B ) were managed with a bifurcated endograft placed by conventional open surgery ( 42 femoral triangles ) . Data concerning all 40 patients were collected prospect ively and analyzed . RESULTS The technical success rate was 92 % ( group A ) vs 90 % ( group B ) , P=0.79 . The incidence of perioperative complications was 16 % ( 3/19 ) in group A and 14 % ( 3/21 ) in group B ( P=0.89 ) . The mean hospital stay was 5.8 days in group A and 7.8 days in group B ( P=0.05 ) . The difference in the length of hospitalisation was associated with reduced cost for the percutaneous group ( 5579.60 euros vs. 7503.60 euros ; P=0.04 ) , that counterbalanced the cost induced by the Prostar XL((R ) ) suture mediated device . Mean follow-up in both groups was 12 months . The overall incidence of locoregional complications after one year of follow-up was 11 % ( 2/19 ) in group A and 19 % ( 4/21 ) in group B ( P=0.45 ) . CONCLUSION This study confirms the feasibility and safety of total percutaneous endovascular AAA repair . Our preliminary results suggest that the costs paid by healthcare providers for endovascular AAA repair might not be increased with the selective use of percutaneous closure devices Endovascular exclusion of abdominal aortic aneurysms ( AAAs ) was developed in an effort to treat patients who were at high risk for complications following st and ard surgical repair . Stent grafts used for endovascular repair of AAAs require the use of large‐bore sheaths and surgical exposure of the common femoral arteries ( CFAs ) . To decrease the invasiveness of AAA repair , we attempted to perform the procedure percutaneously utilizing the Prostar XL Percutaneous Vascular Surgery Device and the preclose technique . Thirty patients underwent an attempted percutaneous AAA repair . These patients were followed prospect ively to assess the success of the procedure . Twenty‐eight patients ( 93 % ) had successful percutaneous repair of both CFA access sites . One patient had inadequate hemostasis of the 22 Fr CFA entry site and one patient had inadequate hemostasis of the 16 Fr CFA entry site . Both of these CFA sites underwent open surgical repair . The rate of successful repair of the 22 Fr CFA access site was 29 of 30 ( 96 % ) ; for the 16 Fr CFA access site , 29 of 30 ( 96 % ) . No in‐hospital groin complications were seen . The procedure time was 105 ± 21 min . The estimated blood loss was 90.6 ± 50 cc . The hemoglobin loss was 1.54 ± 0.89 mg/dL and the hematocrit loss was 5.04 % ± 2.8 % . Complete percutaneous endoluminal AAA repair is feasible using the preclose technique . CFAs with sheaths up to 22 Fr can be safely and successfully accessed and repaired percutaneously using this technique . This method provides secure hemostasis and reduces the invasiveness of procedures requiring large‐bore sheaths . Cathet Cardiovasc Intervent 2002;55:281–287 . © 2002 Wiley‐Liss , PURPOSE To evaluate prospect ively the safety and efficacy of totally percutaneous placement of abdominal and thoracic aortic endografts using the Prostar XL suture-mediated closure system . METHODS From January 2002 to January 2005 , we attempted to insert percutaneously all bifurcated abdominal aortic and thoracic endografts . Consecutive patients ( 25 men , four women ) , with mean age 74.9 years ( range 44 - 84 ) , underwent endovascular repair for 20 abdominal aortic aneurysms ( AAA ) and nine thoracic aortic aneurysms ( repeat operation in one case ) . Endografts used included 21 Zenith ( Cook ) , eight Talent ( Medtronic ) Output:	Moreover , percutaneous endovascular aneurysm repair did not increase the risk of haematoma , pseudoaneurysm , and arterial thrombosis or dissection . Conclusion Percutaneous access demonstrates advantages over conventional surgical exposure for endovascular aneurysm repair , as indicated by access-related complications and hospital length of stay .
MS21882	*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 / Aims : Primary repair of a large hiatal hernia is associated with a published recurrence rate of up to 10 % ; anecdotal rates even higher than this have been reported to the authors . The use of prosthetic material in the repair of other abdominal wall defects has often produced better results than primary repair . We wanted to compare laparoscopic primary repair of large hiatus hernias with laparoscopic primary repair reinforced with prosthetic . Methods : Thirty-one patients with symptomatic gastroesophageal reflux and a hiatal defect 8 cm or greater were r and omized to Nissen fundoplication with posterior cruroplasty ( n = 16 ) or Nissen cruroplasty , and onlay of polytetrafluoroethylene ( PTFE ) mesh ( n = 15 ) . All patients underwent preoperative esophagogastroduodenoscopy ( EGD ) and barium esophagography . After posterior cruroplasty with interrupted nonabsorbable suture , the mesh reinforcement group had an onlay of PTFE placed around the hiatus . A radial slit with 3 cm ‘ keyhole ’ ( to accommo date the esophagus ) was cut into the PTFE . The prosthetic was stapled to the diaphragm , and the two leaves of the slit were stapled to each other . All patients underwent EGD at 3 months and all had esophagrams every 6 months postoperatively . Follow-up ranged from 12 to 36 months . Results : Length of hospital stay was equal in both groups ( 2 days ) . The average cost to the patient with PTFE was USD 1,050 higher than to the patient with primary repair . There were 2 complications ( 1 pneumonia , 1 urinary retention ) in the PTFE group , and 1 complication ( pneumothorax ) in the primary repair group . There were 3 recurrences ( 18.8 % ) in the primary group ( p = 0.08 , χ2 test ) . Conclusion : The use of PFTE reinforcement for primary repair of large hiatal hernias may result in a lower rate of recurrent herniation compared to primary repair alone BACKGROUND Recent reports suggest that when laparoscopy is used to repair paraesophageal hernias recurrence rates reach 20 % to 40 % . Tension-free hernia closure with synthetic mesh reduces recurrence but occasionally results in esophageal injury . We hypothesized that reinforcement of the hiatal closure with small intestine submucosa ( SIS ) mesh , in some unusually large hernias , might reduce recurrence rates without causing injury to the esophagus . METHODS From January 2001 to March 2002 we treated 18 large paraesophageal hernias via a laparoscopic approach . In 9 of the largest hernias ( one type II and 8 type III , of which 1 was recurrent ) the repair was reinforced with SIS mesh ( Surgisis , Cook Surgical ) and represent the subjects of this study . Nissen fundoplication with gastropexy was performed in all patients . Clinical follow-up ranged from 3 to 16 months ( median 8) . Every patient was evaluated with barium esophagram or endoscopy or both 1 to 8 months ( median 2 ) postoperatively . RESULTS The presenting symptoms were postpr and ial pain/fullness ( 9 of 9 ) , heartburn ( 4 of 9 ) , anemia ( 4 of 9 ) , dysphagia ( 3 of 9 ) , regurgitation ( 3 of 9 ) , and chest pain ( 3 of 9 ) . One patient died of a hemorrhagic stroke within 30 days of the operation . Postoperatively , presenting symptoms resolved ( 83 % ) or improved ( 17 % ) in each of the remaining 8 patients . One patient required endoscopic dilation for mild dysphagia . Seven of 8 patients had a normal barium esophagram without evidence of hernia . One morbidly obese ( body mass index = 47 ) patient had a small ( 2 cm ) sliding hiatal hernia postoperatively . There were no other complications , and specifically no perforations or mesh erosions . CONCLUSIONS These observations suggest that the use of SIS in the repair of paraesophageal hernias is safe and may reduce recurrence . Longer follow-up and a r and omized study are needed to vali date these results HYPOTHESIS Large hiatal hernias are prone to disruption , result ing in reherniation , when repaired with simple cruroplasty . The use of mesh may decrease the rate of reherniation in the laparoscopic repair of large hiatal hernias . DESIGN Prospect i ve , r and omized controlled trial . SETTING University-affiliated private hospital . PATIENTS Seventy-two individuals undergoing laparoscopic Nissen fundoplication with a hernia defect greater or equal to 8 cm in diameter . INTERVENTION Nissen fundoplication with posterior cruroplasty ( n = 36 ) vs Nissen fundoplication with posterior cruroplasty and onlay of polytetrafluoroethylene ( PTFE ) mesh ( n = 36 ) . MAIN OUTCOME MEASURES Recurrences , complications , hospital stay , operative time , and cost . RESULTS Patients in both groups had similar hospital stays , but the PTFE group had a longer operative time . The cost of the repair was $ 960 + /- $ 70 more in the group with the prosthesis . Complications were minor and similar in both groups . There were 8 hernia recurrences ( 22 % ) in the primary repair group and none in the PTFE group ( P<.006 ) . CONCLUSION The use of prosthetic reinforcement of cruroplasty in large hiatal hernias may prevent hernia recurrences Abstract Background : Several studies have shown that large hiatal hernias are associated with a high recurrence rate . Despite the problem of recurrence , the technique of hiatal herniorrhaphy has not changed appreciably since its inception . In this 3-year study we have evaluated laparoscopic hiatal hernia repair in individuals with a hernia defect greater than 8 cm in diameter . Methods : A series of 35 patients with sliding or paraesophageal hiatal hernias was prospect ively r and omized to hiatal hernia repair with ( n= 17 ) or without ( n= 18 ) polytetrafluoroethylene ( PTFE ) . All patients had an endoscopic and radiographic diagnosis of large hiatal hernia . Both repairs were performed by using interrupted stitches to approximate the crurae . In the group r and omized to repair with prosthesis , PTFE mesh with a 3-cm ` ` keyhole ' ' was positioned around the gastroesophageal junction with the esophagus through the keyhole . The PTFE was stapled to the diaphragm and crura with a hernia stapler . Results : Patients were followed with EGD and esophagogram at 3 months postoperatively , and with esophagogram every 6 months thereafter . Individuals with PTFE had a longer operation time , but the 2-day hospital stay was the same in both groups . The cost of the repair was $ 1050 ± $ 135 more in the group with the prosthesis . There were two complications ( 1 pneumonia , 1 urinary retention ) in the group repaired with PTFE and one complication ( pneumothorax ) in the group without prosthesis . The group without PTFE was notable for three ( 16.7 % ) recurrences within the first 6 months of surgery . Conclusion : On the basis of these preliminary results it appears that repair with PTFE may confer an advantage , with lower rates of recurrence in patients with large hiatal hernia defects Background The use of mesh for laparoscopic repair of large hiatal hernias may reduce recurrence rates in comparison with primary suture repair . However , there is a potential risk of mesh-related oesophageal complications due to prosthesis erosion . The aim of this study was to evaluate a lightweight polypropylene mesh ( TiMesh ) repair of hiatal hernias with particular reference to intraluminal erosion . Methods Data were collected prospect ively on 18 consecutive patients undergoing elective laparoscopic repair of a large hiatal hernia with the use of TiMesh between November 2004 and December 2005 . Quality of life and symptom analysis was performed using QOLRAD question naires preoperatively and postoperatively after 6 weeks , 6 months , 1 year and 2 years . Barium studies were performed preoperatively and 2 years postoperatively to assess hernia recurrence . After 2 years , oesophagogastric endoscopy was performed to assess signs of mesh-related complications . Results All operations were completed laparoscopically . There was no 30-day mortality and median hospital stay was 2.8 days ( range 2–13 days ) . Complications occurred in two patients ( 11 % ) , both of whom were treated without residual disability . Two years after hiatal hernia repair , there was significant improvement in quality -of-life scores ( QOLRAD 5.79 , p < 0.001 ) . There was no difference between pre- and postoperative dysphagia scores . No signs of stricture formation or prosthetic erosion were identified during endoscopic follow-up . One patient had a small ( 2 cm ) sliding hiatal hernia demonstrated by barium studies , which was asymptomatic . Conclusions Laparoscopic reinforcement of primary hiatal closure with TiMesh leads to a durable repair in patients with large hiatal hernias . Endoscopic follow-up did not show any signs of mesh-related complications after prosthetic reinforcement of the crural repair . Our preliminary results suggest that it is safe to proceed with this lightweight polypropylene mesh for reinforcement of the hiatal repair Background The use of mesh for laparoscopic repair of large hiatal hernias may reduce recurrence rates in comparison to primary suture repair . However , there is a potential risk of mesh-related oesophageal complications due to prosthesis erosion . The aim of this study was to critically evaluate a novel mesh ( DualMesh ) repair of hiatal hernias with particular reference to intraluminal erosion . Method Medical records of 19 patients who underwent laparoscopic hiatal hernia repair with DualMesh reinforcement of the crural closure were review ed from a prospect ively collected data base . Quality of life and symptom analysis was performed using quality of life in reflux and dyspepsia ( QOLRAD ) question naires pre- and postoperatively after 6 weeks , 6 months , 1 year and 2 years . Barium studies were performed on patients pre-operatively and two years postoperatively to assess hernia recurrence . After 2 years , oesophagogastric endoscopy was performed to assess signs of erosion . Results Mean patient age was 70.5 years ( range 49–85 years ) . Two years after hiatal hernia repair , there was significant improvement in quality -of-life scores ( QOLRAD : p < 0.001 ) . Follow-up barium studies performed at 31.3 months ( range 29–40 months ) after surgery showed moderate recurrent hernias ( > 4 cm ) in 1/14 patients ( 7 % ) . Endoscopies performed at 34.4 months ( range 28–41 months ) after surgery did not show any signs of prosthetic erosion . Conclusion Laparoscopic reinforcement of primary hiatal closure with DualMesh leads to a durable repair in patients with large hiatal hernias . Long-term endoscopic follow-up did not show any signs of mesh erosion after prosthetic reinforcement of the crural repair HYPOTHESIS Laparoscopic repair of large hiatal hernia is an appropriate management strategy . DESIGN A prospect i ve patient series . SETTING A university teaching hospital . PATIENTS All patients with hiatal hernias 10 cm or greater in diameter repaired laparoscopically between February 1 , 1992 , and September 30 , 1998 . INTERVENTIONS Two operative strategies were used for laparoscopic repair : the first , which was used until early 1996 , entailed initial esophageal dissection while leaving the sac in the mediastinum . The second involved preliminary dissection of the hernial sac from the mediastinum before dissecting the esophagus . MAIN OUTCOME MEASURES Successful completion of the procedure using a laparoscopic technique , postoperative complication rate , reoperation rate , and clinical outcome . RESULTS Eighty-six patients with a large hiatal hernia underwent attempted repair using laparoscopic methods . The median age was 63 years ( range , 30 - 91 years ) , and 45 patients ( 52 % ) were women . There were 30 sliding , 10 rolling , and 46 mixed hiatal hernias . Operating times ranged from 48 to 240 minutes ( median , 90 minutes ) , and 20 procedures ( 23 % ) were converted to an open operation . Conversion was significantly more common in the first half of our experience ( 16 [ 40 % ] of 40 patients vs 4 [ 9 % ] of 46 patients ) before the operative strategy was changed . Esophageal-lengthening procedures were not carried out for any patient . At follow-up of a median of 2 years , 1 patient has moderate dysphagia , 4 patients have reflux symptoms , and 1 patient has undergone further surgery for a recurrent paraesophageal hernia . An overall satisfactory outcome was achieved in 81 patients ( 94 % ) . CONCLUSIONS Large hiatal hernias can be treated effectively laparoscopically . Dissecting the sac fully from the mediastinum before dissecting the esophagus helps to safely mobilize the esophagus , and we think changing to this Output:	Conclusions The use of mesh in the repair of large hiatal hernias is promising with respect to the reduction of anatomical recurrences .
MS21883	*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 aim of the study was to develop a menopause-specific , preference-based health-related quality -of-life ( HRQoL ) index reflecting both menopausal symptoms and potential side-effects of Hormone Replacement Therapy ( HRT ) . Methods The study had three phases : the development of a health state classification , a prospect i ve valuation survey and the estimation of a model to interpolate HRQoL indices for all remaining health states as defined by the classification . A menopausal health state classification was developed with seven dimensions : hot flushes , aching joints/muscles , anxious/frightened feelings , breast tenderness , bleeding , vaginal dryness and undesirable and rogenic signs . Each dimension contains between three and five levels and defines a total of 6,075 health states . A sample of 96 health states was selected for the valuation survey . These states were valued by a sample of 229 women aged 45 to 60 , r and omly selected from 6 general practice lists in Sheffield , UK . Respondents were asked to complete a time trade-off ( TTO ) task for nine health states , result ing in an average of 16.5 values for each health state . Results Mean health states valued range from 0.48 to 0.98 ( where 1.0 is full health and zero is for states regarded as equivalent to death ) . Symptoms , as described by the classification system , can be rank-ordered in terms of their impact ( from high to low ) on menopausal HRQoL as follows : aching joints and muscles , bleeding , breast tenderness , anxious or frightened feelings , vaginal dryness , and rogenic signs . Hot flushes did not significantly contribute to model fit . The preferred model produced a mean absolute error of 0.053 , but suffered from bias at both ends of the scale . Conclusion This article presents an attempt to directly value a condition specific health state classification . The overall fit was disappointing , but the results demonstrate that menopausal symptoms are perceived by patients to have a significant impact on utility . The overall effect is modest compared to the more generic health state descriptions such as the EQ-5D . The result ant algorithm generates a preference-based index that can be used economic evaluation and that reflects the impact of this condition To estimate patient preferences for gallstone-related treatments and outcomes , and assess how preferences vary by patient characteristics and scaling technique , the authors r and omly assigned 40 patients without gallstones to interviews based on a rating scale ( n = 22 ) and a st and ard gamble ( n = 18 ) . The patients assigned preference values ( possible values 0 to 1 ) to open cholecystectomy ( mean 0.45 by rating scale , 0.78 by st and ard gamble ) , laparoscopic cholecystectomy ( 0.71 , 0.91 ) , extracorporeal shock-wave lithotripsy ( 0.77 , 0.89 ) , acute cholecystitis ( 0.36 , 0.77 ) , lifetime biliary colic ( 0.41 , 0.71 ) , postcholecystectomy syn drome ( 0.43 , 0.79 ) , asymptomatic stone necessitating treatment with bile acids ( 0.76 , 0.96 ) , and surgical scar ( 0.79 , 0.998 ) . Preferences varied little by age , gender , or race . St and ard gamble values were highly correlated with , but significantly greater than , rating scale values . The authors conclude that patients ' preferences for gallstone-related conditions generally are significantly less than one , and differ markedly by the scaling technique used to derive them . These results should be considered when patient preferences are incorporated into analyses of gallstone treatments . Key words : patient preference values ; rating scale ; stan dard gamble ; gallstones ; cholecystectomy ; lithotripsy . ( Med Decis Making 1994;14:307- 314 Background . Health-related quality of life can be measured by patients ' health preferences ( utilities or values ) . No method for measuring health state preferences has been st and ardized for children with arthritis or other musculoskeletal disorders ( MSKDs ) . Such a method is needed for economic evaluations of current and new pediatric treatments . Objectives . 1 ) To assess the feasibility of utility measurements in children with MSKDs , 2 ) to test the validity of the Health Utility Index ( HUI ) for these children , 3 ) to assess whether rating scale values can be mathematically converted into meaningful st and ard gamble ( SG ) utilities , and 4 ) to study whether parents can act as proxies for their children with respect to health state preferences . Methods . Eighty parents of children with MSKDs were consecutively sample d. Their children , if 8 years of age or older ( n = 55 ) , were studied concurrently . Utilities of current health states were obtained by using the SG and the HUI in r and om order . In addition , health state preferences were assessed using categorical and analog rating scales . Traditional nonutility measures of health status ( the Childhood Health Assessment Question naire [ CHAQ ] and the Activities Scale for Kids [ ASK ] ) were also completed . Intraclass correlation coefficients ( ICCs ) were calculated to assess concordance between the different utility measures and also between the ratings of the parents and their children . Results . Children 8 years of age or older were able to express the strength of their health state preferences using the HUI and rating scales . Children older than 10 years of age were able to use the SG method . The health state utilities of the parents were higher than those of their children . The utilities varied widely depending on the elicitation method . The expected high agreement between the SG and the HUI was not found ( ICC = 0.028 for parents , ICC = 0.016 for patients ) . Unlike the SG , the global utilities derived from the HUI agreed better with preferences derived from rating scales ( ICC = 0.23 - 0.25 ) and correlated with traditional health status measures ( with CHAQ , r = -0.56 ; with ASK , r = 0.46 ) both for parents and children . It was not possible to mathematically convert rating scale preferences into SG utilities . The SG utilities were unrelated to results from the rating scales , the CHAQ , and the ASK . Especially for parents , the SG utilities were very high , even when ratings of the other measures indicated poor health . Conclusions . Although it is possible to measure health utilities for children with MSKDs , the results are highly method dependent . The properties of the HUI in this population are more like those of the traditional health status measures rather than those of the SG . Preferences derived from rating scales , although easily performed , can not readily be converted into SG utilities . Parents ' ratings for their children are impaired by risk aversion This article explores various method ological issues of patient utility measurement in two r and omized controlled clinical trials involving 85 patients with fibromyalgia and 144 with ankylosing spondylitis . In both trials one baseline and two follow-up measurements of the patients ' preferences for their own health state and several hypothetical states were performed using the rating scale and the st and ard gamble methods .It was confirmed that st and ard gamble scores are consistently higher than rating scale scores for both the experienced and the hypothetical states . The 3-month test-retest reliability for hypothetical states measured by intraclass correlation coefficients ranged from 0.24 to 0.33 for the rating scale and from 0.43 to 0.70 for the st and ard gamble . Although the reproducibility is not high , the group mean scores are fairly stable over time . Mean st and ard gamble scores tend to differ depending on the way the measurements are undertaken . Utilities elicited with chained gambles were significantly higher than utilities elicited with basic reference gambles . At the individual level some inconsistent responses occurred . However , more than 70 % of these fell within the bounds of the measurement error , which ranged from 0.11 to 0.13 on the st and ard gamble ( 0–1 scale ) and from 8 to 10 on the rating scale ( 0–100 scale ) . The large number of negative utilities for the severe hypothetical state , which was used as an anchor point in the chained gambles , and the magnitude of these negative utilities ( down to −19 ) calls for intensified research efforts to h and le these responses in utility calculations The techniques of cost utility analysis ( CUA ) were used to evaluate the treatment of gallstone disease by open and laparoscopic cholecystectomy and by extracorporeal shockwave lithotripsy ( ESWL ) . The application of the techniques in this context raised three method ological questions which are not satisfactorily resolved in the literature . The first is whether an ex ante or ex post perspective is best adopted for the measurement of quality of life ( QoL ) . The second is the method for converting a short term deterioration in QoL followed by full health into QALYs and the reliability of the methods available . The third is the issue of indirect costs which , in the context of a temporary disease state , can not be easily avoided . The economic evaluation found laparoscopic cholecystectomy to be generally superior than the competitor technologies ( entailing lower costs and better outcomes ) . However , the results were sensitive to assumptions about the perspective for measuring benefits and the inclusion of indirect costs Measuring preferences for schizophrenia outcomes facilitates meaningful integration of multiple outcome measures and multiple perspectives on treatment outcomes . The Time Tradeoff ( TTO ) technique , specifically developed for measuring health state preferences , is used widely in health research , but some evidence suggests that the TTO may work less well with schizophrenia than with other health conditions . This study tested the hypotheses that tailoring the time frame of the st and ard TTO to the course of schizophrenia and simplifying its presentation fromat would improve its feasibility and efficiency . Forty clinicians provided TTO ratings using 1 of 4 combinations of time frame and presentation format . Numeric ratings and quantitative and qualitative measures of feasibility showed that while participants preferred the simpler format , none of the alterations improved feasibility . Participants ' ratings were prone to logical inconsistencies and participants found all 4 versions of the TTO confusing and poorly suited to the context of schizophrenia treatment Objective To obtain quality -of-life ( QOL ) valuations associated with mammography screening and breast cancer treatment that are suitable for use in cost-effectiveness analyses . Methods Subjects comprised 131 women ( age range 50–79 years ) r and omly sample d from a breast cancer screening program . In an in-person or telephone interview , women rated the QOL impact of 14 clinical scenarios ( ranging from mammography to end-of-life care for breast cancer ) using a visual analogue scale anchored by death ( 0 ) and perfect health/ quality of life ( 100 ) . Results Women rated the scenarios describing true negative results , false positive results , and routine screening mammography at 80 or above on a scale of 0–100 , suggesting that they perceive these states as being close to perfect health . They rated adjuvant chemotherapy ( 39.7 ; range 10–90 ) , palliation/end-of-life care ( 35.8 ; range 0–100 ) , and recurrence at 1 year ( 33.0 ; range 0–95 ) the lowest , suggesting that these health states are perceived as compromised . Women rated receiving news of a breast cancer diagnosis ( true positive ) ( 45.7 ; range 5–100 ) and receiving delayed news of a breast cancer diagnosis ( false negative ) ( 48.5 ; range 5–100 ) as being comparable to undergoing mastectomy ( 48.3 ; range 10–100 ) and radiation therapy ( 46.2 ; range 5–100 ) for breast cancer . Conclusions These data can be used to up date cost analyses of mammography screening that wish to take into account the QOL impact of screening OBJECTIVE To examine preterm , near-term , and term mothers ' self-reported quality of life in the early postpartum period . DESIGN Prospect i ve , longitudinal repeated measures design . SETTING Four medical centers in the Midwest . PATIENTS / PARTICIPANTS A convenience sample of 184 mothers of either a preterm , near-term , or term infant . MAIN OUTCOME MEASURE Maternal Postpartum Quality of Life tool . RESULTS Mothers of preterm infants scored significantly lower on the subscale psychological/baby of the Maternal Postpartum Quality of Life tool compared to mothers of near-term and term infants . CONCLUSIONS Infant gestational age at birth has relevance for maternal quality of life during the postpartum period . Health care professionals need to be cognizant relative to infant gestational age and individualize nursing care Output:	In using adapted techniques , the primary challenge was identifying an appropriate intermediate " anchor " HS and the possibility of negative utilities . CONCLUSIONS There is no agreement on the most method ologically robust approach to THS valuation .
MS21884	*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 Inhalation of hypertonic saline ( HTS ) has short term positive effects on airways clearance in non-cystic fibrosis ( CF ) bronchiectasis , however its long term effects are unknown . The aim of this study was to determine the effect of HTS 6 % on exacerbations , quality of life ( QOL ) and respiratory function over 12 months in non-CF bronchiectasis . METHODS Forty patients were r and omised to inhale isotonic saline ( IS ) 0.9 % or HTS 6 % daily for 12 months . Participants recorded their symptoms in a daily diary . Quality of life and respiratory function were measured after three , six and 12 months . Number of exacerbations and changes in sputum colonisation were recorded at 12 months . Participants , assessors and clinicians were blinded to group allocation . RESULTS The exacerbation rate at 12 months was similar in the two groups and similar clinical ly significant improvements in QOL were seen in both groups . The FEV(1 ) increased in both groups after six months ( mean 90 ml , 95 % confidence interval 11 - 169 ml ) with no difference between groups ( p = 0.394 ) . The FEF(25 - 75 % ) significantly improved at all time points ( mean increase at 12 months 187 ml , 69 - 304 ml ) with no difference between groups ( p = 0.705 ) . There was a reduction in sputum colonisation in both groups ( p = 0.046 ) . CONCLUSIONS Inhalation of HTS or IS has similar effects on exacerbations , QOL , sputum colonisation and respiratory function over 12 months in non-CF bronchiectasis . The trial was registered with both Clinical Trials.gov - NCT00484263 and Australian New Zeal and Clinical Trials Registry - ACTRN12607000367448 BACKGROUND Inhaled dry powder mannitol enhanced mucus clearance and improved quality of life over 2 weeks in non-cystic fibrosis bronchiectasis . This study 's objective was to investigate the efficacy and safety of dry powder mannitol over 12 weeks . METHODS Patients with bronchiectasis confirmed by high-resolution CT ( H RCT ) scan , aged 15 to 80 years , with FEV1≥50 % predicted and ≥1 L participated in a r and omized , placebo-controlled , double-blind study . Patients with a negative mannitol provocation test were r and omized to inhale 320 mg mannitol ( n=231 ) or placebo ( n=112 ) bid for 12 weeks . To further assess safety , the same mannitol dose/frequency was administered to a patient subset in an open-label extension over 52 weeks . Primary end points were changes from baseline at 12 weeks in 24-h sputum weight and St. George 's Respiratory Question naire ( SGRQ ) score . RESULTS There was a significant difference of 4.3 g in terms of change in sputum weight over 12 weeks ( 95 % CI , 1.64 - 7.00 ; P=.002 ) between mannitol and placebo ; however , this was largely driven by a decrease in sputum weight in the placebo group . This was associated , in turn , with more antibiotic use in the placebo group ( 50 of 112 [ 45 % ] ) than in the inhaled mannitol group ( 85 of 231 [ 37 % ] ) . There was no statistical difference between the groups ( P=.304 ) in total SGRQ score ( mannitol , -3.4 points [ 95 % CI , -4.81 to -1.94 ] vs placebo , -2.1 points [ 95 % CI , -4.12 to -0.09 ] ) . In a subgroup study ( n=82 ) , patients receiving mannitol showed less small airway mucus plugging on H RCT scan at 12 weeks compared with patients receiving placebo ( P=.048 ) . Compliance rates were high , and mannitol was well tolerated with adverse events similar to those of placebo . CONCLUSION Because the difference in sputum weights appears to be associated with increased antibiotic use in the placebo group , a larger controlled study is now required to investigate the long-term mannitol effect on pulmonary exacerbations and antibiotic use . TRIAL REGISTRY Clinical Trials.gov ; No. : NCT0027753 ; URL : www . clinical trials.gov RATIONALE Bronchiectasis is a chronic debilitating disease with few evidence -based long-term treatments . OBJECTIVES A r and omized controlled trial assessing the efficacy of nebulized gentamicin therapy over 1 year in patients with non-cystic fibrosis bronchiectasis . METHODS Sixty-five patients were r and omized to either twice-daily nebulized gentamicin , 80 mg , or nebulized 0.9 % saline , for 12 months . All were review ed at three-monthly intervals during treatment and at 3 months ' follow-up . MEASUREMENTS AND MAIN RESULTS At each review the following were assessed : quantitative and qualitative sputum bacteriology ; sputum purulence and 24-hour volume ; FEV(1 ) , FVC , and forced expiratory flow , midexpiratory phase ; exercise capacity ; Leicester Cough Question naire and St. George 's Respiratory Question naire ; and exacerbation frequency . Fifty-seven patients completed the study . At the end of 12 months ' treatment , compared with the saline group , in the gentamicin group there was reduced sputum bacterial density with 30.8 % eradication in those infected with Pseudomonas aeruginosa and 92.8 % eradication in those infected with other pathogens ; less sputum purulence ( 8.7 % vs. 38.5 % ; P < 0.0001 ) ; greater exercise capacity ( 510 [ 350 - 690 ] m vs. 415 [ 267.5 - 530 ] m ; P = 0.03 ) ; and fewer exacerbations ( 0 [ 0 - 1 ] vs. 1.5 [ 1 - 2 ] ; P < 0.0001 ) with increased time to first exacerbation ( 120 [ 87 - 161.5 ] d vs. 61.5 [ 20.7 - 122.7 ] d ; P = 0.02 ) . The gentamicin group had greater improvements in Leicester Cough Question naire ( 81.4 % vs. 20 % ; P < 0.01 ) and St. George 's Respiratory Question naire ( 87.5 % vs. 19.2 % ; P < 0.004 ) score . No differences were seen in 24-hour sputum volume , FEV(1 ) , FVC , or forced expiratory flow , midexpiratory phase . No P. aeruginosa isolates developed resistance to gentamicin . At follow-up , all outcome measures were similar to baseline . CONCLUSIONS Regular , long-term nebulized gentamicin is of significant benefit in non-cystic fibrosis bronchiectasis but treatment needs to be continuous for its ongoing efficacy . Clinical trial registered with www . clinical trials.gov ( NCT 00749866 ) BACKGROUND Inhaled hypertonic saline acutely increases mucociliary clearance and , in short-term trials , improves lung function in people with cystic fibrosis . We tested the safety and efficacy of inhaled hypertonic saline in a long-term trial . METHODS In this double-blind , parallel-group trial , 164 patients with stable cystic fibrosis who were at least six years old were r and omly assigned to inhale 4 ml of either 7 percent hypertonic saline or 0.9 percent ( control ) saline twice daily for 48 weeks , with quinine sulfate ( 0.25 mg per milliliter ) added to each solution to mask the taste . A bronchodilator was given before each dose , and other st and ard therapies were continued during the trial . RESULTS The primary outcome measure , the rate of change ( slope ) in lung function ( reflected by the forced vital capacity [ FVC ] , forced expiratory volume in one second [ FEV1 ] , and forced expiratory flow at 25 to 75 percent of FVC [ FEF25 - 75 ] ) during the 48 weeks of treatment , did not differ significantly between groups ( P=0.79 ) . However , the absolute difference in lung function between groups was significant ( P=0.03 ) when averaged across all post-r and omization visits in the 48-week treatment period . As compared with the control group , the hypertonic-saline group had significantly higher FVC ( by 82 ml ; 95 percent confidence interval , 12 to 153 ) and FEV1 ( by 68 ml ; 95 percent confidence interval , 3 to 132 ) values , but similar FEF25 - 75 values . The hypertonic-saline group also had significantly fewer pulmonary exacerbations ( relative reduction , 56 percent ; P=0.02 ) and a significantly higher percentage of patients without exacerbations ( 76 percent , as compared with 62 percent in the control group ; P=0.03 ) . Hypertonic saline was not associated with worsening bacterial infection or inflammation . CONCLUSIONS Hypertonic saline preceded by a bronchodilator is an inexpensive , safe , and effective additional therapy for patients with cystic fibrosis . ( Clinical Trials.gov number , NCT00271310 . RATIONALE The prevalence of bronchiectasis is high in patients with moderate-to-severe chronic obstructive pulmonary disease ( COPD ) and it has been associated with exacerbations and bacterial colonization . These have demonstrated some degree of prognostic value in patients with COPD but no information about the relationship between bronchiectasis and mortality in patients with COPD is currently available . OBJECTIVES To assess the prognostic value of bronchiectasis in patients with moderate-to-severe COPD . METHODS Multicenter prospect i ve observational study in consecutive patients with moderate-to-severe COPD . Bronchiectasis was diagnosed by high-resolution computed tomography scan . A complete st and ardized protocol was used in all patients covering general , anthrophometric , functional , clinical , and microbiologic data . After follow-up , the vital status was recorded in all patients . Multivariate Cox analysis was used to determine the independent adjusted prognostic value of bronchiectasis . MEASUREMENTS AND MAIN RESULTS Ninety-nine patients in Global Initiative for Chronic Obstructive Lung Disease ( GOLD ) II , 85 in GOLD III , and 17 in GOLD IV stages were included . Bronchiectasis was present in 115 ( 57.2 % ) patients . During the follow-up ( median , 48 mo [ interquartile range , 35 - 53 ] ) there were 51 deaths ( 43 deaths in the bronchiectasic group ) . Bronchiectasis was associated with an increased risk of fully adjusted mortality ( hazard ratio , 2.54 ; 95 % confidence interval , 1.16 - 5.56 ; P = 0.02 ) . CONCLUSIONS Bronchiectasis was associated with an independent increased risk of all-cause mortality in patients with moderate-to-severe COPD Bronchiectasis is characterised by hypersecretion and impaired clearance of mucus . A 400-mg dose of inhaled mannitol improves mucus clearance however , the effect of other doses is unknown . A total of 14 patients , aged 63.3±5.7 yrs , were studied on five visits . Mucus clearance at baseline and with mannitol ( 160 , 320 and 480 mg ) was measured using technetium-99m-sulphur colloid and imaging with a gamma camera over 45 min , followed by a further 30 min involving 100 voluntary coughs . A control study assessed the effect of cough provoked by mannitol during the intervention . Whole right lung clearance over 45 min was 4.7±1.2 and 10.6±2.6 % on baseline and control days , respectively , and increased to 16.7±4.2 , 22.8±4.2 and 31±4.7 % with 160 , 320 and 480 mg mannitol , respectively . Clearance over 45 min with 480 mg mannitol was greater than clearance with 320 and 160 mg . Total clearance over 75 min , after mannitol administration and voluntary coughs , was 36.1±5.5 , 40.9±5.6 and 46.0±5.2 % with 160 , 320 and 480 mg mannitol , respectively , all significantly different from baseline ( 24.1±6.0 % ) and control ( 13.1±3.0 % ) . Total clearance over 75 min with 480 mg mannitol was greater compared with 160 mg . In conclusion , mucus clearance increases with increasing doses of mannitol and can be further increased by cough in patients with bronchiectasis The effects of broad-spectrum antibiotic and placebo therapy in patients with chronic obstructive Output:	There is an indication from a single , large , unpublished study that inhaled mannitol increases time to first exacerbation in patients with bronchiectasis . In patients with near normal lung function , spirometry does not change dramatically with mannitol and adverse events are not more frequent than placebo .
MS21885	*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: We developed a comprehensive and culturally applicable empowerment intervention social self-value package with an aim to assess its efficacy in order to improve the quality of life ( QoL ) of HIV infected people receiving antiretroviral treatment . Participants were r and omly allocated to receive either six weekly intervention sessions or st and ard care . Nonlinear mixed-effects models were performed to compare changes in empowerment scores over time . Between September and November 2014 , 1447 individuals were screened , of whom 132 were r and omly assigned to either the intervention or control group . The mean scores of empowerment , social support and quality of life increased and stigma scores were reduced in the intervention group at 3- and 6-months . An intervention effect on social support , stigma and QoL was significantly increased by time and group with low and high empowerment . No adverse events were reported . The empowerment intervention was efficacious in improving QoL of HIV infected people . ResumenHemos desarrollado un fortalecimiento completo y cultural applicable a la intervención social del paquete del valor propio con la intención de evaluar su eficacia para mejorar la calidad de vida de las personas infectadas por el VIH que están recibiendo ART . A los participantes se les adjudicó aleatoriamente la asignación de seis dosis semanales o los cuidados est and ar . El result ado de los efectos se presentó para comparar los cambios en los valores del fortalecimiento a lo largo del tiempo . Entre septiembre y noviembre de 2014 , 1447 individuos fueron moritonizados , de los cuales 132 fueron aleatoriamente asignados para cada intervención o grupo de control . La media del valor del fortalecimiento , apoyo social y calidad de vida incrementaron y los valores del estigma fueron reducidos en la intervención grupal entre 3 y 6 meses . Los efectos de una intervención al apoyo social , estigma y calidad de vida se incrementaron significativamente en ese periodo y el grupo con un bajo y alto fortalecimiento . No hubo efectos secundarios notificados . La intervención en el fortalecimiento fue satisfactoria en la mejora de la calidad de vida de la gente infectada por el VIH HIV-related stigma among persons living with HIV/AIDS ( PLHIV ) is prevalent throughout sub-Saharan Africa . There is limited evidence , however , on which interventions are effective in reducing it . We used data from a prospect i ve impact evaluation of a 12-month food assistance intervention among 904 antiretroviral therapy (ART)- naïve PLHIV in Ug and a to examine the program impact on stigma . Stigma was measured using the comprehensive HASI-P scale , which demonstrated good internal consistency ( Cronbach ’s alpha = 0.87 ) and was correlated with several related constructs including physical and mental health-related quality of life , disclosure , and physical health symptoms in the sample . Using quasi-experimental difference-in-difference matching methods to better infer causality , we tested whether the intervention improved the overall stigma scale and its subscales . The food assistance intervention had a significant effect on reported internalized ( but not external ) stigma of approximately 0.2 SD ( p < 0.01 ) . The HASI-P stigma scale is a useful tool for measuring and tracking stigma . Food assistance interventions , embedded in an HIV care program , can reduce internalized stigma This study sought to explore , describe and determine whether an HIV stigma-reduction community “ hub ” intervention would change the HIV stigma experiences of people living with HIV ( PLWH ) and the stigmatisation by the community in an urban area in South Africa . A convergent parallel mixed- method design with a single case pre-test post-test design and an interpretive description approach was utilised . The sample for this study included 62 PLWH recruited through accessibility sampling and 570 community members recruited through r and om voluntary sampling . A sub- sample of both groups , selected using purposive voluntary sampling , was utilised for the in-depth interviews about stigma experiences of PLWH , and for perceptions and attitudes of the community toward PLWH . Both quantitative and qualitative data showed that stigma is present . Although no statistically significant changes were found , small practically significant changes were demonstrated in the experiences of PLWH and in the perceptions and attitudes of the community . The extent of changes was much more obvious in the responses of the PLWH and the community during their post-intervention qualitative interviews than the changes found with the quantitative measures . This study thus concludes that the HIV stigma-reduction community hub intervention was successful in initiating the onset of changes in a community through the PLWH and people living close to PLWH ( PLC ) as community mobilisers active in the community hub to mobilise their own communities towards HIV stigma reduction through social change The authors of this study evaluated a structured 10-session psychosocial support group intervention for newly HIV-diagnosed pregnant South African women . Participants were expected to display increases in HIV disclosure , self-esteem , active coping and positive social support , and decreases in depression , avoidant coping , and negative social support . Three hundred sixty-one pregnant HIV-infected women were recruited from four antenatal clinics in Tshwane townships from April 2005 to September 2006 . Using a quasi-experimental design , assessment s were conducted at baseline and two and eight months post-intervention . A series of r and om effects regression analyses were conducted , with the three assessment points treated as a r and om effect of time . At both follow-ups , the rate of disclosure in the intervention group was significantly higher than that of the comparison group ( p < 0.001 ) . Compared to the comparison group at the first follow-up , the intervention group displayed higher levels of active coping ( t = 2.68 , p < 0.05 ) and lower levels of avoidant coping ( t = −2.02 , p < 0.05 ) , and those who attended at least half of the intervention sessions exhibited improved self-esteem ( t = 2.11 , p < 0.05 ) . Group interventions tailored for newly HIV positive pregnant women , implemented in re source -limited setting s , may accelerate the process of adjusting to one 's HIV status , but may not have sustainable benefits over time Abstract Background We evaluate the impact of clinic-based PMTCT community support by trained lay health workers in addition to st and ard clinical care on PMTCT infant outcomes . Methods In a cluster r and omized controlled trial , twelve community health centers ( CHCs ) in Mpumalanga Province , South Africa , were r and omized to have pregnant women living with HIV receive either : a st and ard care ( SC ) condition plus time-equivalent attention-control on disease prevention ( SC ; 6 CHCs ; n = 357 ) , or an enhanced intervention ( EI ) condition of SC PMTCT plus the “ Protect Your Family ” intervention ( EI ; 6 CHCs ; n = 342 ) . HIV-infected pregnant women in the SC attended four antenatal and two postnatal video sessions and those in the EI , four antenatal and two postnatal PMTCT plus “ Protect Your Family ” sessions led by trained lay health workers . Maternal PMTCT and HIV knowledge were assessed . Infant HIV status at 6 weeks postnatal was drawn from clinic PCR records ; at 12 months , HIV status was assessed by study administered DNA PCR . Maternal adherence was assessed by dried blood spot at 32 weeks , and infant adherence was assessed by maternal report at 6 weeks . The impact of the EI was ascertained on primary outcomes ( infant HIV status at 6 weeks and 12 months and ART adherence for mothers and infants ) , and secondary outcomes ( HIV and PMTCT knowledge and HIV transmission related behaviours ) . A series of logistic regression and latent growth curve models were developed to test the impact of the intervention on study outcomes . Results In all , 699 women living with HIV were recruited during pregnancy ( 8–24 weeks ) , and assessment s were completed at baseline , at 32 weeks pregnant ( 61.7 % ) , and at 6 weeks ( 47.6 % ) , 6 months ( 50.6 % ) and 12 months ( 59.5 % ) postnatally . Infants were tested for HIV at 6 weeks and 12 months , 73.5 % living infants were tested at 6 weeks and 56.7 % at 12 months . There were no significant differences between SC and EI on infant HIV status at 6 weeks and at 12 months , and no differences in maternal adherence at 32 weeks , reported infant adherence at 6 weeks , or PMTCT and HIV knowledge by study condition over time . Conclusion The enhanced intervention administered by trained lay health workers did not have any salutary impact on HIV infant status , ART adherence , HIV and PMTCT knowledge . Trial registration clinical trials.gov : number ABSTRACT The ANRS 12249 Treatment-as-Prevention ( TasP ) cluster-r and omized trial in rural South Africa uses a “ test and treat ” approach . Home-based testing services and antiretroviral treatment initiation satellite clinics were implemented in every cluster as part of the trial . A social science research agenda was nested within TasP with the aim of underst and ing the social , economic and context ual factors that affect individuals , households , communities and health systems with respect to TasP. Considering the rural nature of the trial setting , we sought to underst and community perceptions and experiences of the TasP Trial interventions as seen through the eyes of traditional health practitioners ( THPs ) . A qualitative study design was adopted using four repeat focus group discussion s conducted with nine THPs , combined with community walks and photo-voice techniques , over a period of 18 months . A descriptive , interpretive and explanatory approach to analysis was adopted . Findings indicate that THPs engaged with the home-based testing services and HIV clinics established for TasP. Specifically , home-based testing services were perceived as relatively successful in increasing access to HIV testing . A major gap observed by THPs was linkage to HIV clinics . Most of their clients , and some of the THPs themselves , found it difficult to use HIV clinics due to fear of labelling , stigma and discrimination , and the ensuing personal implication s of unsolicited disclosure . On the one h and , a growing number of patients diagnosed with HIV have found sanctuary with THPs as alternatives to clinics . On the other h and , THPs in turn have been struggling to channel patients suspected of HIV into clinics through referrals . Therefore , acceptability of the TasP test and treat approach by THPs is a major boost to the intervention , but further success can be achieved through strengthened ties with communities to combat stigma and effectively link patients into HIV care , including partnerships with THPs themselves Introduction Injecting drug use is a primary driver of HIV epidemics in many countries . People who inject drugs ( PWID ) and are HIV infected are often doubly stigmatized and many encounter difficulties reducing risk behaviors . Prevention interventions for HIV-infected PWID that provide enhanced support at the individual , family , and community level to facilitate risk-reduction are needed . Methods 455 HIV-infected PWID and 355 of their HIV negative injecting network members living in 32 sub-districts in Thai Nguyen Province were enrolled . We conducted a two-stage r and omization : First , sub-districts were r and omized to either a community video screening and house-to-house visits or st and ard of care educational pamphlets . Second , within each sub-district , participants were r and omized to receive either enhanced individual level post-test counseling and group support sessions or st and ard of care HIV testing and counseling . This result ed in four arms : 1 ) st and ard of care ; 2 ) community level intervention ; 3 ) individual level intervention ; and 4 ) community plus individual intervention . Follow-up was conducted at 6 , 12 , 18 , and 24 months . Primary outcomes were self-reported HIV injecting and sexual risk behaviors . Secondary outcomes included HIV incidence among HIV negative network members . Results Fewer participants reported sharing injecting equipment and unprotected sex from baseline to 24 months in all arms ( 77 % to 4 % and 24 % to 5 % respectively ) . There were no significant differences at the 24-month visit among the 4 arms ( Wald = 3.40 ( 3 df ) ; p = 0.33 ; Wald = 6.73 ( 3 df ) ; p = 0.08 ) . There were a total of 4 HIV seroconversions over 24 months with no significant difference between intervention and control arms . Discussion Underst and ing the mechanisms through which all arms , particularly the control arm , demonstrated both low risk behaviors and low HIV incidence has important implication s for policy and prevention programming . Trial Registration Clinical Trials.gov Background Among people living with HIV ( PLHIV ) on antiretroviral therapy ( ART ) , it is important to determine how quality of life ( QOL ) may be improved and HIV-related stigma can be lessened over time . This study assessed the effect of peer support on QOL and internal stigma during the first year after initiating ART among a cohort of PLHIV in north-eastern Vietnam . Methods A sub- sample study of a r and omised controlled trial was implemented between October 2008 and November 2010 in Quang Ninh , Vietnam . In the intervention group , participants ( n = 119 ) received adherence support from trained peer supporters who visited participants ’ houses biweekly during the first two months , thereafter weekly . In the control group , participants ( n = 109 ) were treated according to st and ard guidelines , including adherence counselling , monthly health check and drug refills . Basic demographics were measured at baseline . QOL and internal stigma were measured using a Vietnamese version of the WHOQOL-HIVBREF and Internal AIDS-related Stigma Scale instruments at baseline and 12 months . T- Output:	Conclusion Structural interventions such as scale-up of antiretroviral treatment , prevention of medication stockouts , social empowerment and economic strengthening may help substantially reduce self-stigma among individuals .
MS21886	*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 purpose of this study was to conduct a r and omized clinical trial to assess whether a self-management group intervention can improve mood , self-efficacy , and activity in people with central vision loss due to age-related macular degeneration ( AMD ) . Ninety-two elderly patients with AMD ( average age=79 ) from a university ophthalmology clinic were r and omly assigned to the self-management intervention ( n=44 ) or to a wait-list ( n=48 ) . All patients were legally blind in at least one eye . The intervention consisted of 6 weekly 2-hour group sessions providing education about the disease , group discussion , and behavioral and cognitive skills training to address barriers to independence . All participants eventually completed the intervention allowing pre-post comparisons for all patients . The battery of measures included the Profile of Mood States ( POMS ) ; Quality of Well-Being Scale ; and assessment s of self-efficacy , participation in activities , and use of vision aids . Participants ' initial psychological distress was high ( mean total POMS=59.72 ) and similar to distress experienced by other serious chronic illness population s ( e.g. cancer , bone marrow transplant ) . Analysis of covariance testing the primary hypothesis revealed that intervention participants experienced significantly ( p=.04 ) reduced psychological distress ( pre $ $ \bar x = 61.45$$ ; post $ $ \bar x = 51.14$$ ) in comparison with wait-list controls ( pre $ $ \bar x = 57.72$$ ; post $ $ \bar x = 62.32$$ ) . Intervention participants also experienced improved ( p=.02 ) self-efficacy ( pre $ $ \bar x = 70.16$$ ; post $ $ \bar x = 77.27$$ ) in comparison with controls ( pre $ $ \bar x = 67.71$$ ; post $ $ \bar x = 69.07$$ ) . Further , intervention participants increased their use of vision aids ( p<.001 ; pre $ $ \bar x = 3.37$$ , post $ $ \bar x = 6.69$$ ) . This study demonstrates that a relatively brief behavioral intervention can substantially reduce psychological distress and increase self-efficacy in elderly adults experiencing vision loss due to macular degeneration . Self-management intervention appears to improve mood , self-efficacy , and use of vision aids , further enhancing the lives of poorly sighted individuals with AMD OBJECTIVE To determine whether problem-solving treatment ( PST ) can prevent depressive disorders in patients with age-related macular degeneration ( AMD ) . DESIGN Two hundred six patients with AMD were r and omly assigned to PST ( n = 105 ) or usual care ( n = 101 ) . PST therapists delivered six PST sessions over 8 weeks in subjects ' homes . MEASUREMENTS Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition Diagnoses of Depressive Disorders , Hamilton Depression Rating Scale scores , and rates of relinquishing valued activities were assessed at 2 months for short-term effects and 6 months for maintenance effects . RESULTS The 2-month incidence rate of depressive disorders in PST-treated subjects was significantly lower than controls ( 11.6 % versus 23.2 % , respectively ; OR = 0.43 ; 95 % CI [ 0.20 , 0.95 ] ) . PST also reduced the odds of relinquishing a valued activity ( OR = 0.48 ; 95 % CI [ 0.25 , 0.96 ] ) ; this effect mediated the relationship between treatment group and depression . By 6 months most earlier observed benefits had diminished . Secondary analyses showed that a minimal level of depressive symptoms were disabling and predicted incident depressive disorders . CONCLUSION PST prevented depressive disorders and loss of valued activities as a short-term treatment but these benefits were not maintained over time . To sustain PST 's effect , an intervention that uses a problem-solving framework to enhance rehabilitative skills may be necessary AIMS --A survey was undertaken to assess the effectiveness of an integrated approach to the provision of low visual aids ( LVAs ) in south Devon over a 2 year follow up period . This integrated approach includes the assessment of patient needs by low vision therapists , followed by the provision of suitable LVAs , with particular emphasis on training in their use . METHODS --A total of 125 patients were selected at r and om from the 445 patients seen in the low vision clinic at Torbay Hospital in the year 1991 . These patients were sent question naires relating to the service over a 2 year period . Question naires from 111 patients were analysed at 1 year and 75 question naires together with 46 clinical re assessment s , after 2 years . RESULTS --Using a similar question naire to one used in a previous study in the UK from a unit where LVA training was not provided , not only was a higher rate of satisfaction found with the services provided , but also the LVAs dispensed were used more frequently . The majority of the LVAs provided were of the simple , inexpensive variety and wastage was very low . CONCLUSIONS --It was concluded that this integrated approach to low vision rehabilitation with emphasis on training in the use of less complex LVAs exceeds the performance of other types of service that rely on the dispensing of more complex LVAs Aim : To compare the effectiveness of three models of low vision rehabilitation for people with age related macular degeneration ( AMD ) referred for low vision rehabilitation ( LVR ) : ( a ) an enhanced low vision rehabilitation model ( ELVR ) including supplementary home based low vision rehabilitation ; ( b ) conventional low vision rehabilitation ( CLVR ) based in a hospital clinic ; ( c ) CLVR with home visits that did not include rehabilitation ( CELVR ) , intended to act as a control for the additional contact time with ELVR . Method : A single centre parallel group r and omised controlled trial in participants ’ homes and the low vision clinic , Manchester Royal Eye Hospital . People referred for LVR with a primary diagnosis of AMD and visual acuity worse than 6/18 in both eyes and equal to or better than 1/60 in the better eye . The main outcome measures were vision specific quality of life ( QoL ) ( primary outcome , VCM1 ) and generic health related QoL ( SF-36 ) ; psychological adjustment to vision loss ; measured task performance ; restriction in everyday activities ; use of low vision aids ( LVAs ) . Results : 226 participants were recruited ( median age 82 years ) ; 194 completed the trial ( 86 % ) . Except for SF-36 physical and mental component summary scores , arms did not differ significantly for any of the outcomes . Differences for the VCM1 were ELVR v CLVR , 0.06 ( 95 % CI to 0.17 to 0.30 , p = 0.60 ) ; ELVR v CELVR , 0.12 ( 95 % CI to 0.11 to 0.34 , p = 0.31 ) ; CELVR v CLVR , –0.05 ( 95 % CI –0.29 to 0.18 , p = 0.64 ) . Differences for the SF-36 favoured CLVR compared to ELVR ( ELVR v CLVR : physical = –6.05 , 95 % CI –10.2 to –1.91 , p = 0.004 ; mental = –4.04 , 95 % CI –7.44 to –0.65 , p = 0.02 ) . At 12 months , 94 % of participants reported using at least one LVA . Conclusion : ELVR was no more effective than CLVR . Research ers should be wary of proposing new LVR interventions without preliminary evidence of effectiveness , given the manifest lack of effectiveness of the model of enhanced LVR evaluated in the trial PURPOSE : To test the hypothesis that vision rehabilitation using optometry , occupational therapy and social work services increases patients ' functional ability and to assess whether involving families in the intervention results in more successful outcomes . METHODS : We conducted an outcome study of 97 patients new to the Vision Rehabilitation Service . Subjects were between the ages of 19 and 91 years , with a median age of 76 . Their visual acuities were 20/100 or worse in the better eye , with 50 % of the subjects having acuities worse than 20/200 . Macular degeneration was the most prevalent diagnosis . Subjects were assigned to either an individually focused ( n=48 ) or a family focused ( n=49 ) intervention . The outcome measure was change in function , as assessed by speed and accuracy of performance ( objective measure ) and by the patients ' self-reports of difficulty and dependency in performing daily activities ( subjective measures ) . Data were collected before and after the intervention . RESULTS : Most patients had documented improvement after rehabilita-tion on both objective ( p=.0001 ) and subjective ( decreased dependency , p=.01 ) measures of function . The sample size did not provide adequate statistical power to show differences between family focused and individually focused interventions . CONCLUSIONS : This study documents significant improvement after vision rehabilitation for a predominately elderly population . Patients in both family and individually focused interventions improved comparably Purpose . ( 1 ) to document participation in daily activities and social roles of older adults seeking services for visual impairment ( VI ) and compare it with that of the older population without VI or other disabilities , and ( 2 ) to explore correlates of their participation . Methods . The 64 participants ( 46 women ) had an average age of 79.3 years ( SD = 5.9 years ) and presented various types of VI . Participants were interviewed at home to collect information regarding their visual function ( National Eye Institute Visual Function Question naire-25 ) , sociodemographic and clinical characteristics , including depressive symptoms ( Geriatric Depression Scale ) , and participation ( Assessment of Life Habits/LIFE-H ) . Each participant was matched with another person without disabilities r and omly recruited from the community . Results for the two population s on the Life-H participation domains were compared using t-tests . In the group with VI , general information ( independent variables ) was examined in relation to participation main scores ( dependent variables ) , followed by multiple linear regression analyses . Results . Participation in daily activities and social roles of participants with VI ( mean ± SD ( /9 ) = 6.8 ± 1.0 and 5.6 ± 1.6 , respectively ) was significantly lower than that of participants without VI ( 8.1 ± 0.4 and 8.3 ± 0.4 ) ( p < 0.0001 ) . Depressive symptoms and perceived quality of distance vision were the strongest correlates and together explained more than 65 % of the variance in the participation scores of the subjects with VI . Conclusions . This study demonstrates the participation restrictions associated with VI and underlines the importance of psychological aspects in participation PURPOSE The study has investigated the effect of lighting on the daily activities ( ADL ) of the visually impaired in their homes by comparison before and after light adjustments were made in the kitchen , hall and bathroom . It has also investigated the additional effects on the quality of life after providing task lighting in the living room . METHOD A total of 56 people were consecutively recruited from those receiving lighting adaptation help by the Low Vision Clinic in Göteborg . Ten persons did not complete the study . After medical examinations , lighting st and ards and psychosocial factors were charted . After lighting improvements were carried out in the kitchen , hall and bathroom , the subjects were r and omly divided into two groups , an intervention and a comparison group . The task lighting in the living room was also improved for those included in the intervention group . Follow-up interviews to determine ADL and quality of life were performed 6 months after lighting adaptation . RESULTS A marked effect on quality of life of the lighting in the living room was found for the intervention group . The effect on ADL of the basic lighting adaptation in kitchen , hall and bathroom for both groups was significant for tasks carried out on the working surface in the kitchen . Other activities in the kitchen and in the bathroom tended to improve but changes were not significant . CONCLUSION The results confirm that it is possible to increase quality of life by improving the lighting conditions OBJECTIVE The purpose of this r and omized , longitudinal study was to investigate the impact of a health education program on perceived security in the performance of daily occupations 4 months after the intervention period . METHOD Two groups of persons with age-related macular degeneration were compared : Those who had followed a newly developed health education program that was based on occupation and those who took part in a st and ard individual intervention program . RESULTS Significant differences in the level of perceived security between the groups were found for 13 of 28 occupations . Participants in the health education group maintained or improved their level of perceived security in 22 daily occupations , whereas those in the individual intervention group declined to a lower level in 17 daily occupations . CONCLUSION This study provides support for the effectiveness of the health education program to enhance security and hinder a progressive decline in perceived security in daily occupations Output:	The strongest evidence supports using a problem-solving approach to improve leisure and social participation for older adults with low vision . Evidence was moderate supporting the delivery of a combination of services , either by one professional or through an interdisciplinary approach .
MS21887	*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 PURPOSE The goal of the present study was to examine the re source and economic implication s of an early hospital discharge and home-based rehabilitation scheme for patients with acute stroke . METHODS A cost minimization analysis in conjunction with a r and omized controlled trial was carried out at 2 affiliated teaching hospitals in the southern metropolitan region of Adelaide , South Australia , between 1997 and 1998 . Eighty-six hospitalized patients with acute stroke who required rehabilitation were r and omized to receive both early hospital discharge and home-based rehabilitation , or conventional in-hospital rehabilitation and community care . Direct and indirect costs related to stroke rehabilitation were calculated , including hospital bed days , home-based intervention program , community services , and personal expenses during the 6 months after r and omization . RESULTS The mean cost per patient was lower for patients r and omized to the early hospital discharge and home-based rehabilitation ( $ 8040 ) compared with those who received conventional care ( $ 10 054 ) . This cost saving was not statistically significant ( P=0.14 ) . However , sensitivity analyses indicated that the cost of home-based rehabilitation was consistently lower than that of conventional care except when hospital costs were assumed to be 50 % less than those used in the main analysis . Multiple regression analysis demonstrated that the cost of the home-based program was significantly related to a patient 's level of disability after adjustment for age , comorbidity , and the presence or absence of a caregiver . CONCLUSIONS The early hospital discharge and home-based rehabilitation scheme was less costly than conventional hospital care for patients with stroke . Limitation of the provision of such services to patients with mild disability is likely to be most cost effective Background and Purpose — Early supported discharge ( ESD ) for stroke has been shown to yield outcomes similar to or better than those of conventional care , but there is less information on the impact on costs and on the caregiver . The purpose of this study is to estimate the costs associated with an ESD program compared with those of usual care . Methods — We conducted a r and omized controlled trial of stroke patients who required rehabilitation services and who had a caregiver at home . Results — Acute-care costs incurred before r and omization when patients were medically ready for discharge averaged $ 3251 per person . The costs for the balance of the acute-care stay , from r and omization to discharge , were $ 1383 for the home group and $ 2220 for the usual care group . The average cost of providing the 4-week home intervention service was $ 943 per person . The total cost generated by persons assigned to the home group averaged $ 7784 per person , significantly lower than the $ 11 065 per person for those assigned to usual care . A large proportion of the cost differential between the 2 groups arose from readmissions , for which the usual care group generated costs more than quadruple those of the home intervention group . Conclusions — Providing care at home was no more ( or less ) expensive for those with greater functional limitation than for those with less . Caregivers in the ESD group scored consistently lower on the Burden Index than caregivers with usual care , even caregivers of persons with major functional limitations . For persons recovering from stroke and their families , ESD provides a cost-effective alternative to usual care BACKGROUND AND PURPOSE In an inner-London teaching hospital , a r and omized trial of " conventional " care versus early discharge to community-based therapy found no significant differences in clinical outcomes between patient groups . This report examines the economic consequences of the alternative strategies . METHODS One hundred sixty-seven patients received the early discharge package , and 164 received conventional care . Patient utilization of health and social services was recorded over a 12-month period , and cost was determined using data from provider departments and other published sources . RESULTS Inpatient stay after r and omization was 12 days ( intervention group ) versus 18 days ( controls ) ( P=0.0001 ) . Average units of therapy per patient were as follows : physiotherapy , 22.4 ( early discharge ) versus 15.0 ( conventional ) ( P=0.0006 ) ; occupational therapy , 29.0 versus 23.8 ( P=0.002 ) ; speech therapy , 13 . 7 versus 5.8 ( P=0.0001 ) . The early discharge group had more annual hospital physician contacts ( P=0.015 ) and general practitioner clinic visits ( P=0.019 ) but fewer incidences of day hospital attendance ( P=0.04 ) . Other differences in utilization were nonsignificant . Average annual costs per patient were pound sterling 6800 ( early discharge ) and pound sterling 7432 ( conventional ) . The early discharge group had lower inpatient costs per patient ( pound sterling 4862 [ 71 % of total cost ] versus pound sterling 6343 [ 85 % ] for controls ) but higher non-inpatient costs ( pound sterling 1938 [ 29 % ] versus pound sterling 1089 [ 15 % ] ) . Further analysis demonstrated that early discharge is unlikely to lead to financial savings ; its main benefit is to release capacity for an expansion in stroke caseload . CONCLUSIONS Overall results of this trial indicate that early discharge to community rehabilitation for stroke is cost-effective . It may provide a means of addressing the predicted increase in need for stroke care within existing hospital capacity Background and Purpose The aim of the present study was to examine re source utilization during a 12-month period after acute stroke in elderly patients r and omized to care in an acute stroke unit integrated with a care continuum compared with conventional care in general medical wards . A secondary aim was to describe costs related to the severity of stroke . Methods Two hundred forty-nine consecutive patients aged ≥70 years with acute stroke within 7 days before admission , living in their own homes in Göteborg , Sweden , without recognized need of care were r and omized to 2 groups : 166 patients were assigned to nonintensive stroke unit care with a care continuum , and 83 patients were assigned to conventional care . There was no difference in mortality or the proportion of patients living at home after 1 year . Main outcomes were costs from inpatient care , outpatient care , and informal care . Results Mean annual cost per patient was 170 000 Swedish crowns ( SEK ) ( equivalent to $ 25 373 ) and 191 000 SEK ( $ 28 507 ) in the stroke unit and the general medical ward groups , respectively ( P = NS ) . Seventy percent of the total cost was for inpatient care , and 30 % was for outpatient and informal care . For patients with mild , moderate , and severe stroke , the mean annual costs per patient were 107 000 SEK ( $ 15 970 ) , 263 000 SEK ( $ 39 254 ) , and 220 000 SEK ( $ 32 836 ) , respectively ( P < 0.001 ) . There was no statistical difference in age or nonstroke diagnosis . Conclusions The total costs the first year did not differ significantly between the treatment groups in this prospect i ve study . The total annual cost per patient showed a very large variation , which was related to stroke severity at onset and not to age or nonstroke diagnoses . Costs other than those for hospital care constituted a substantial fraction of total costs and must be taken into account when organizing the management of stroke patients . The high variability in costs necessitates a larger study to assess long-term cost effectiveness Background and Purpose — Although stroke units reduce mortality and institutionalization , their comparative cost-effectiveness is unknown . Methods — Healthcare , social services , and informal care costs were compared for 447 acute stroke patients r and omly assigned to stroke unit , stroke team , or domiciliary stroke care . Prospect i ve and retrospective methods were used to identify re source use over 12 months after stroke onset . Cost-effectiveness and cost-utility analyses were undertaken . Results — Mean healthcare and social care costs over 12 months were £ 11 450 for stroke unit , £ 9527 for stroke team , and £ 6840 for domiciliary care . More than half the costs were for the initial episode of care . Institutionalization was a large proportion of follow-up costs . Inclusion of informal care increased costs considerably . When informal care was excluded , the incremental cost-effectiveness ratio per percentage point in deaths or institutionalizations avoided in the first year was £ 496 for the stroke unit over domiciliary care ; incremental cost per quality -adjusted life year quality -adjusted life year gained was £ 64 097 between these 2 groups . The stroke team was dominated by domiciliary care . Conclusions — Cost perspectives , especially those related to long-term and informal care , are important when stroke services are evaluated . Improved health outcomes in the stroke unit come at a higher cost Background and Purpose — Level I evidence from r and omized controlled trials demonstrates that the model of hospital care influences stroke outcomes ; however , the economic evaluation of such is limited . An economic appraisal of 3 acute stroke care models was facilitated through the Stroke Care Outcomes : Providing Effective Services ( SCOPES ) study in Melbourne , Australia . The aim was to describe re source use up to 28 weeks poststroke for each model and examine the cost-effectiveness of stroke care units ( SCUs ) . Methods — A prospect i ve , multicenter , cohort study design was used . Costs and outcomes of stroke patients receiving 100 % treatment in 1 of 3 inpatient care models ( SCUs , mobile service , conventional care ) were compared . Health-sector re source use up to 28 weeks was measured in 1999 . Outcomes were thorough adherence to a suite of important clinical processes and the number of severe inpatient complications . Results — The sample comprised 395 participants ( mean age 73 [ SD 14 ] , 77 % first-ever strokes , males 53 % ) . When compared with conventional care ( n=84 ) , costs for mobile service ( n=209 ) were significantly higher ( P=0.024 ) , but borderline for SCU ( n=102 , P=0.08 ; $ AUD12 251 ; $ AUD15 903 ; $ AUD15 383 respectively ) . This was primarily explained by the greater use of specialist medical services . The incremental cost-effectiveness of SCUs over conventional care was $ AUD9867 per patient achieving thorough adherence to clinical processes and $ AUD16 372 per patient with severe complications avoided , based on costs to 28 weeks . Conclusions — Although acute SCU costs are generally higher , they are more cost-effective than either mobile service or conventional care BACKGROUND AND PURPOSE Treatment of stroke patients in specialized stroke units has become more frequent , yet the effect of this treatment has not been determined . METHODS In a community-based , prospect i ve , and consecutive study of 1241 unselected acute stroke patients , we compared outcome of stroke treatment between two neighboring communities within Greater Copenhagen : the Bispebjerg community , where all acute stroke patients are treated and rehabilitated on a stroke unit , and Frederiksberg community , where all acute stroke patients are treated and rehabilitated on general neurological and medical wards . Except for the different organization of stroke treatment , the two communities and the two patient groups were comparable . Specifically , age , sex , marital status , prestroke residence , and stroke severity were not statistically different between patients treated on the stroke unit and those treated on the general neurological and medical wards . Multivariate regression analyses were used to estimate the independent influence of stroke unit treatment on outcome . RESULTS Stroke unit treatment significantly reduced in-hospital mortality ( odds ratio [ OR ] , 0.50 ; 95 % confidence interval [ CI ] , 0.34 to 0.74 ; P < .001 ) , case-fatality rate ( OR , 0.45 ; CI , 0.28 to 0.71 ; P < .001 ) , 6-month mortality ( OR , 0.57 ; CI , 0.39 to 0.82 ; P = .002 ) , 1-year mortality ( OR , 0.59 ; CI , 0.42 to 0.84 ; P = .003 ) , and discharge rate to a nursing home ( OR , 0.61 ; CI , 0.38 to 0.98 ; P = .04 ) . Discharge rate to the patient 's own home was significantly increased ( OR , 1.90 ; CI , 1.30 to 2.70 ; P < .001 ) . The length of hospital stay ( including rehabilitation ) was reduced significantly by 30 % in patients treated on the stroke unit despite their lower mortality ( P < .001 ) . The savings due to stroke unit treatment were estimated at 1313 bed-days and three places at a nursing home per 100 stroke patients . CONCLUSIONS Treatment of unselected acute stroke patients on a stroke care unit saved lives , reduced the length of hospital stay , reduced the frequency of discharge to a nursing home , and potentially reduced cost Background and Purpose Several trials have shown that stroke unit care improves outcome for stroke patients . The aim of the present trial was to evaluate the effects of an extended stroke unit service ( ESUS ) , with early supported discharge , cooperation with the primary healthcare system , and more emphasis on rehabilitation at home as essential elements . Methods In a r and omized , controlled trial , 160 patients with acute stroke were allocated to the ESUS and 160 to the ordinary stroke unit service ( OSUS ) . The primary outcome was the proportion of patients who were independent as assessed by the modified Rankin Scale ( RS ) ( RS ≤2=global independence ) and independent in activities of daily living ( ADL ) as assessed by Barthel Index ( BI ) ( BI ≥95=independent in ADL ) after 26 weeks . Secondary outcomes were RS and BI scores after 6 weeks ; the proportion of patients Output:	Home-based rehabilitation is unlikely to lead to cost-savings , but achieves better health outcomes . Care in stroke units is more expensive than conventional care , but leads to improved health outcomes . The cost-effectiveness studies on integrated stroke services suggest that they can reduce costs .
MS21888	*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 combined hyperlipemia have lipid abnormalities associated with an increased tendency to develop atherosclerosis and thrombosis . This tendency may be accelerated during postpr and ial hyperlipemia . In the present double-blind parallel study , 41 patients with combined hyperlipemia and serum triacylglycerols between 2.0 and 15.0 mmol/L and serum total cholesterol > 5.3 mmol/L at the end of a 3-month dietary run-in period were treated with simvastatin at 20 mg/d for at least 10 weeks ; patients were then r and omized into 2 groups receiving simvastatin+omega-3 fatty acids at 3.36 g/d or placebo ( corn oil ) for an additional 5 weeks . Hemostatic variables that have been associated with increased thrombotic tendency were evaluated with subjects in the fasting state and during postpr and ial hyperlipemia before and after combined treatment . Supplementation of omega-3 fatty acid reduced tissue factor pathway inhibitor antigen ( P<0.05 ) in the fasting state , reduced the degree of postpr and ial hyperlipemia ( P<0.005 ) , and reduced activated factor VII concentration appearing during postpr and ial hyperlipemia . In conclusion , omega-3 fatty acids given in addition to simvastatin to patients with combined hyperlipemia reduced the free tissue factor pathway inhibitor fraction in the fasting state and inhibited the activation of factor VII occurring during postpr and ial lipemia , thus representing a potential beneficial effect on the hemostatic risk profile in this patient group Hypercholesterolemia is combined with enhanced lipid peroxidation , which can promote atherogenesis by inducing endothelial adhesion molecule expression . Statins may protect vascular endothelium in hypercholesterolemia by reducing enhanced plasma levels of low-density lipoprotein and decreasing oxidative stress . Herein , we describe increased circulating levels of soluble intercellular adhesion molecule-1 , vascular cell adhesion molecule-1 , and E-selectin and total 8-iso-prostagl and in F(2 alpha ) ( 8-iso-PGF(2 alpha ) ) concentrations , as indexes of endothelial activation and lipid peroxidation , respectively , in 67 hypercholesterolemic patients compared with 32 normocholesterolemic subjects . Significant cholesterol reductions were achieved in hypercholesterolemic patients after 6 months under either simvastatin ( 40 mg/d ) or bezafibrate ( 800 mg/d ) treatment , given according to a r and omized double-blind trial . Simvastatin but not bezafibrate simultaneously reduced soluble adhesin and total 8-iso-PGF(2 alpha ) concentrations also . Vitamin E supplementation ( 400 IU/d ) further reduced indexes of endothelial activation and lipid peroxidation in simvastatin-treated patients and significantly reduced the above indexes in bezafibrate-treated patients . Changes in circulating soluble adhesion molecule levels were directly correlated with changes in total 8-iso-PGF(2 alpha ) concentrations in simvastatin-treated patients also receiving vitamin E supplementation . All together , our data demonstrated that hypercholesterolemia was combined with endothelial activation and lipid peroxidation , which were efficaciously counteracted by simvastatin but not bezafibrate treatment . Thus , a different vascular protection can be achieved by different lipid-lowering treatments The objective of the study was to evaluate potential benefits of docosahexaenoic acid ( DHA ) rich fish oil supplementation as an adjunct to statin therapy for hyperlipidaemia . A total of 45 hyperlipidaemic patients on stable statin therapy with persistent elevation of plasma triglycerides ( averaging 2.2 mmol/L ) were r and omised to take 4 g/day ( n = 15 ) or 8 g/day ( n = 15 ) of tuna oil or olive oil ( placebo , n = 15 ) for 6 months . Plasma lipids , blood pressure and arterial compliance were assessed initially and after 3 and 6 months in 40 subjects who completed the trial . Plasma triglycerides were reduced 27 % by 8 g/day DHA-rich fish oil ( P < 0.05 ) but not by 4 g/day when compared with the placebo and this reduction was achieved by 3 months and was sustained at 6 months . Even though total cholesterol was already well controlled by the statin treatment ( mean initial level 4.5 mmol/L ) , there was a further dose-dependent reduction with fish oil supplementation ( r = −0.344 , P < 0.05 ) . The extent of total cholesterol reduction correlated ( r = −0.44 ) with the initial total cholesterol levels ( P < 0.005 ) . In the subset with initial plasma cholesterol above 3.8 mmol/L , plasma very low density lipoprotein ( VLDL ) , intermediate-density lipoprotein ( IDL ) and low-density lipoprotein ( LDL ) were isolated and assayed for cholesterol and apolipoprotein B ( apoB ) at the commencement of the trial and at 3 months of intervention . Fish oil tended to lower cholesterol and apoB in VLDL and raise both in LDL . There were no changes in IDL cholesterol , IDL apoB and high-density lipoprotein cholesterol . The results demonstrate that DHA-rich fish oil supplementation ( 2.16 g DHA/day ) can improve plasma lipids in a dose-dependent manner in patients taking statins and these changes were achieved by 3 months . Fish oil in addition to statin therapy may be preferable to drug combinations for the treatment of combined hyperlipidaemia Background The approximately 1100 medical journals now active in China are publishing a rapidly increasing number of research reports , including many studies identified by their authors as r and omized controlled trials . It has been noticed that these reports mostly present positive results , and their quality and authenticity have consequently been called into question . We investigated the adequacy of r and omization of clinical trials published in recent years in China to determine how many of them met acceptable st and ards for allocating participants to treatment groups . Methods The China National Knowledge Infrastructure electronic data base was search ed for reports of r and omized controlled trials on 20 common diseases published from January 1994 to June 2005 . From this sample , a subset of trials that appeared to have used r and omization methods was selected . Twenty-one investigators trained in the relevant knowledge , communication skills and quality control issues interviewed the original authors of these trials about the participant r and omization methods and related quality -control features of their trials . Results From an initial sample of 37,313 articles identified in the China National Knowledge Infrastructure data base , we found 3137 apparent r and omized controlled trials . Of these , 1452 were studies of conventional medicine ( published in 411 journals ) and 1685 were studies of traditional Chinese medicine ( published in 352 journals ) . Interviews with the authors of 2235 of these reports revealed that only 207 studies adhered to accepted methodology for r and omization and could on those grounds be deemed authentic r and omized controlled trials ( 6.8 % , 95 % confidence interval 5.9–7.7 ) . There was no statistically significant difference in the rate of authenticity between r and omized controlled trials of traditional interventions and those of conventional interventions . R and omized controlled trials conducted at hospitals affiliated to medical universities were more likely to be authentic than trials conducted at level 3 and level 2 hospitals ( relative risk 1.58 , 95 % confidence interval 1.18–2.13 , and relative risk 14.42 , 95 % confidence interval 9.40–22.10 , respectively ) . The likelihood of authenticity was higher in level 3 hospitals than in level 2 hospitals ( relative risk 9.32 , 95 % confidence interval 5.83–14.89 ) . All r and omized controlled trials of pre-market drug clinical trial were authentic by our criteria . Of the trials conducted at university-affiliated hospitals , 56.3 % were authentic ( 95 % confidence interval 32.0–81.0 ) . Conclusion Most reports of r and omized controlled trials published in some Chinese journals lacked an adequate description of r and omization . Similarly , most so called ' r and omized controlled trials ' were not real r and omized controlled trials owing toa lack of adequate underst and ing on the part of the authors of rigorous clinical trial design . All r and omized controlled trials of pre-market drug clinical trial included in this research were authentic . R and omized controlled trials conducted by authors in high level hospitals , especially in hospitals affiliated to medical universities had a higher rate of authenticity . That so many non-r and omized controlled trials were published as r and omized controlled trials reflected the fact that peer review needs to be improved and a good practice guide for peer review including how to identify the authenticity of the study urgently needs to be developed Thirty elderly ( mean + /- SEM : 73.8 + /- 2.1 y ) nondiabetic , moderately obese ( body mass index = 28.3 + /- 0.6 kg/m2 ) patients with stable effort angina underwent an oral-glucose-tolerance test and a euglycemic hyperinsulinemic glucose clamp before and after vitamin E supplementation ( 900 mg/d for 4 mo ) . The study was of a r and omized , placebo-controlled , double-blind , and crossover design . Anthropometric indexes were stable throughout the study . Despite similar fasting and 2-h plasma glucose concentrations , vitamin E administration ( compared with placebo ) lowered fasting ( 88 + /- 14 and 68 + /- 9 pmol/L , P < 0.02 ) and 2-h ( 348 + /- 43 and 263 + /- 28 pmol/L , P < 0.05 ) plasma insulin concentrations , plasma triglyceride concentrations ( 1.34 + /- 0.06 and 1.07 + /- 0.03 mmol/L , P < 0.05 ) , and the ratio of plasma LDL to HDL cholesterol ( 7.64 + /- 0.31 and 5.52 + /- 0.38 , P < 0.02 ) . Vitamin E administration was associated with higher nonoxidative glucose metabolism ( 18.1 + /- 0.5 and 10.6 + /- 0.7 mumol.kg lean body mass-1.min-1 , P < 0.03 ) than was placebo administration during the euglycemic glucose clamp . We conclude that chronic intake of pharmacological doses of vitamin E might be useful in the therapy of elderly insulin-resistant patients with coronary heart disease BACKGROUND Supplementation with vitamin E may antagonize vitamin K in healthy adults , but it is unclear whether intake of vitamin E decreases the risk of venous thromboembolism ( VTE ) . METHODS AND RESULTS The Women 's Health Study r and omized 39,876 women > or = 45 years of age to receive 600 IU of natural source vitamin E or placebo on alternate days . Before r and omization , 26,779 participants gave blood sample s , which were used to determine factor V Leiden , G20210A prothrombin , and 677C > T MTHFR polymorphisms . Documented VTE ( including deep vein thrombosis or pulmonary embolism ) and unprovoked VTE ( no recent surgery , trauma , or cancer diagnosis ) were prospect ively evaluated , secondary end points of the trial . During a median follow-up period of 10.2 years , VTE occurred in 482 women : 213 in the vitamin E group and 269 in the placebo group , a significant 21 % hazard reduction ( relative hazard , 0.79 ; 95 % CI , 0.66 to 0.94 ; P=0.010 ) . For unprovoked VTE , the hazard reduction was 27 % ( relative hazard , 0.73 ; 95 % CI , 0.57 to 0.94 ; P=0.016 ) . In subgroup analyses , the 3 % of participants who reported VTE before r and omization had a 44 % hazard reduction ( relative hazard , 0.56 ; 95 % CI , 0.31 to 1.00 ; P=0.048 ) , whereas women without prior VTE had an 18 % hazard reduction ( relative hazard 0.82 ; 95 % CI , 0.68 to 0.99 ; P=0.040 ) . Women with either factor V Leiden or the prothrombin mutation had a 49 % hazard reduction associated with vitamin E treatment ( relative hazard , 0.51 ; 95 % CI , 0.30 to 0.87 ; P=0.014 ) . CONCLUSIONS These data suggest that supplementation with vitamin E may reduce the risk of VTE in women , and those with a prior history or genetic predisposition may particularly benefit BACKGROUND Aged Garlic Extract ( AGE ) reduces multiple cardiovascular risk factors , including blood pressure , cholesterol , platelet aggregation and adhesion , while stimulating nitric oxide generation in endothelial cells . However , no study has evaluated the ability of AGE to inhibit vascular calcification , a marker of plaque formation in human coronary arteries . O Output:	With only a few small studies available per supplement , evidence was insufficient for all predefined gradable clinical efficacy and harms outcomes , such as mortality and serious adverse events . Incremental benefits were noted for triglyceridemia with omega-3 fatty acid added to statins ; and there was an improvement in levels of high-density lipoprotein cholesterol with garlic supplementation when people also consumed nitrates Conclusions Evidence of low-strength indicates benefits of omega-3 fatty acids ( plus statin , or calcium channel blockers and antiplatelets ) and garlic ( plus nitrates or warfarin ) on triglycerides and HDL-C , respectively .
MS21889	*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 Lung cancer patients with mutations in the epidermal growth factor receptor ( EGFR ) are primary c and i date s for EGFR-targeted therapy . Reliable analyses of such mutations have previously been possible only in tumour tissue . Here , we demonstrate that mutations can be detected in plasma sample s with allele-specific PCR assays . Methods Pairs of the diagnostic biopsy and plasma obtained just prior to start of erlotinib treatment were collected from 199 patients with adenocarcinoma of non-small-cell lung cancer . DNA from both sample types was isolated and examined for the presence of mutations in exons 18–21 of the EGFR gene , employing the cobas ® EGFR Tissue Test and cobas ® EGFR Blood Test ( in development , Roche Molecular Systems , Inc. , CA , USA ) . Results Test results were obtained in all 199 ( 100 % ) plasma sample s and 196/199 ( 98 % ) of the biopsies . EGFR-activating mutations were identified in 24/199 ( 12 % ) plasma sample s and 28/196 ( 14 % ) biopsy sample s , and 17/196 ( 9 % ) matched pairs contained the same mutation . Six EGFR mutations were present only in plasma sample s but not in the biopsy sample s. The overall concordance of the EGFR gene mutations detected in plasma and biopsy tissue was 179/196 ( 91 % ) ( kappa value : 0.621 ) . Conclusion Mutational analysis of the EGFR gene in plasma sample s is feasible with allele-specific PCR assays and represents a non-invasive supplement to biopsy analysis .Trial registration M-20080012 from March 10 , 2008 and reported to Clinical Trials.gov : NCT00815971 Cases of non – small-cell lung cancer ( NSCLC ) carrying the somatic mutation of epidermal growth factor receptor ( EGFR ) have been shown to be hyperresponsive to the EGFR tyrosine kinase inhibitor gefitinib ( IRESSA ) . If EGFR mutations can be observed in serum DNA , this could serve as a noninvasive source of information on the genotype of the original tumor cells that could influence treatment and the ability to predict patient response to gefitinib . Serum genomic DNA was obtained from Japanese patients with NSCLC before first-line gefitinib monotherapy . Scorpion Amplified Refractory Mutation System technology was used to detect EGFR mutations . Wild-type EGFR was detected in all of the 27 serum sample s. EGFR mutations were detected in 13 of 27 ( 48.1 % ) patients and two major EGFR mutations were identified ( E746_A750del and L858R ) . The EGFR mutations were seen significantly more frequently in patients with a partial response than in patients with stable disease or progressive disease ( P = 0.046 , Fisher 's exact test ) . The median progression-free survival was significantly longer in patients with EGFR mutations than in patients without EGFR mutations ( 200 versus 46 days ; P = 0.005 , log-rank test ) . The median survival was 611 days in patients with EGFR mutations and 232 days in patients without EGFR mutations ( P > 0.05 ) . In pairs of tumor and serum sample s obtained from 11 patients , the EGFR mutation status in the tumors was consistent with those in the serum of 8 of 11 ( 72.7 % ) of the paired sample s. Thus , EGFR mutations were detectable using Scorpion Amplified Refractory Mutation System technology in serum DNA from patients with NSCLC . These results suggest that patients with EGFR mutations seem to have better outcomes with gefitinib treatment , in terms of progression-free survival , overall survival , and response , than those patients without EGFR mutations Introduction : In IPASS ( IRESSA Pan-Asia Study ) , clinical ly selected patients with pulmonary adenocarcinoma received first-line gefitinib or carboplatin/paclitaxel . This preplanned , exploratory analysis was conducted to increase underst and ing of the use of surrogate sample s , such as serum , versus tumor biopsy sample s for determining EGFR mutation status in the Japanese cohort ( n = 233 ) . Methods : EGFR mutations were assessed using tumor tissue-derived DNA ( n = 91 ) and circulating free ( cf ) DNA from pretreatment serum sample s ( n = 194 ) . Results : Fewer patients were EGFR mutation positive when assessed using pretreatment cfDNA ( 23.7 % ) versus tumor tissue-derived DNA ( 61.5 % ) . cfDNA results identified no false positives but a high rate of false negatives ( 56.9 % ) . There was a significant interaction between cfDNA EGFR mutation status and treatment for progression-free survival ( PFS ) ( p = 0.045 ) . PFS was significantly longer and objective response rate ( ORR ) higher with gefitinib than carboplatin/paclitaxel in the cfDNA EGFR mutation-positive subgroup ( PFS : hazard ratio [ HR ] , 0.29 ; 95 % confidence interval [ CI ] , 0.14–0.60 ; p < 0.001 ; ORR : odds ratio [ OR ] , 1.71 ; 95 % CI , 0.48–6.09 ; 75.0 % versus 63.6 % ; p = 0.40 ) . There was a slight numerical advantage in PFS and ORR for gefitinib over carboplatin/paclitaxel in the cfDNA EGFR mutation-negative subgroup , likely due to the high rate of false negatives within this subgroup . Conclusions : These results merit further investigation to determine whether alternative sources of tumor DNA , such as cfDNA in serum , could be used for determining EGFR mutation status in future ; currently , where a sample is available , analysis of tumor material is recommended PURPOSE Mutations in the epidermal growth factor receptor ( EGFR ) kinase domain can predict tumor response to tyrosine kinase inhibitors ( TKIs ) in non-small-cell lung cancer ( NSCLC ) . However , obtaining tumor tissues for mutation analysis is challenging . We hypothesized that plasma-based EGFR mutation analysis is feasible and has value in predicting tumor response in patients with NSCLC . PATIENTS AND METHODS Plasma DNA sample s and matched tumors from 230 patients with stages IIIB to IV NSCLC were analyzed for EGFR mutations in exons 19 and 21 by using denaturing high-performance liquid chromatography . We compared the mutations in the plasma sample s and the matched tumors and determined an association between EGFR mutation status and the patients ' clinical outcomes prospect ively . RESULTS In 230 patients , we detected 81 EGFR mutations in 79 ( 34.3 % ) of the patients ' plasma sample s. We detected the same mutations in 63 ( 79.7 % ) of the matched tumors . Sixteen plasma ( 7.0 % ) and fourteen tumor ( 6.1 % ) sample s showed unique mutations . The mutation frequencies were significantly higher in never-smokers and in patients with adenocarcinomas ( P = .012 and P = .009 , respectively ) . In the 102 patients who failed platinum-based treatment and who were treated with gefitinib , 22 ( 59.5 % ) of the 37 with EGFR mutations in the plasma sample s , whereas only 15 ( 23.1 % ) of the 65 without EGFR mutations , achieved an objective response ( P = .002 ) . Patients with EGFR mutations had a significantly longer progression-free survival time than those without mutations ( P = .044 ) in plasma . CONCLUSION EGFR mutations can be reliably detected in plasma DNA of patients with stages IIIB to IV NSCLC and can be used as a biomarker to predict tumor response to TKIs Background : The authors evaluate the efficacy and safety of gefitinib monotherapy in chemotherapy-naive patients with advanced non – small-cell lung cancer ( NSCLC ) . A secondary endpoint is to evaluate the relationship between clinical manifestations and epidermal growth factor receptor ( EGFR ) mutation status . Methods : Japanese chemotherapy-naive NSCLC patients were enrolled . They had measurable lesions , Eastern Cooperative Oncology Group performance status of 0 to 2 , and adequate organ and bone marrow function . Patients received 250 mg of oral gefitinib daily . EGFR mutations in exon 18 , 19 , and 21 of DNA extracted from tumor and serum were analyzed by genomic polymerase chain reaction and direct sequence . Results : All 30 patients were eligible for the assessment of efficacy and safety . An objective response and stable disease were observed in 10 patients ( 33.3 % ) and nine patients ( 30.0 % ) , respectively . The median time to progression was 3.3 months and the median overall survival was 10.6 months . The 1-year survival rate was 43.3 % . Grade 3 toxicities were observed in seven patients . EGFR mutation was observed in four of 13 ( 30.8 % ) tumors , and two of them achieved partial response . In serum sample s , three of 10 patients with EGFR mutations in the serum before treatment had a response to gefitinib . EGFR mutation was observed in 10 of 27 and significantly more frequently observed in the posttreatment sample s from patients with a partial response or stable disease than in those from patients with progressive disease ( p = 0.006 ) . Conclusions : Gefitinib monotherapy in chemotherapy-naive NSCLC patients was active , with acceptable toxicities . These results warrant further evaluation of gefitinib monotherapy as a first-line therapy . The EGFR mutation in serum DNA may be a biomarker for monitoring the response to gefitinib during treatment Output:	Conclusions : Although blood had a better specificity for detecting EGFR mutations , the absence of blood positivity should not necessarily be construed as confirmed negativity .
MS21890	*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: Twenty-four healthy adult female volunteers participated in a r and omized , three-phase double-blind crossover trial comparing the single-dose ( 50 mg ) pharmacokinetics of three formulations of clomiphene citrate ( CC ) . Plasma levels of both the Z(cis ) and E(trans ) isomers of CC , as well as principal metabolites , were determined at periodic intervals ; and no differences between formulations were observed . The active Z isomer attained peak blood levels later than the inactive E isomer and was eliminated much more slowly , significant plasma concentrations still being detected up to 1 month after treatment . The results of this study demonstrate that three commercially available formulations of CC are bioequivalent This study evaluates the efficacy of a stimulation protocol with clomiphene citrate (CC)/human menopausal gonadotropin (hMG)/cetrorelix and its effects on oocyte quality and endometrium . One hundred and twenty couples with male-factor infertility who were about to undergo their first intracytoplasmic sperm injection cycles were r and omized into two groups . Sixty women were stimulated with the CC/hMG/cetrorelix protocol ( cetrorelix group ) and 60 received the buserelin long protocol ( buserelin group ) . Fewer oocytes were recovered in the cetrorelix group than in the buserelin group ( mean ± st and ard deviation ( SD ) : 11.1 ± 4.0 vs. 17.3 ± 5.8 , p < 0.001 ) ; however , the percentages of metaphase II , metaphase I and germinal vesicle oocytes were similar between the two groups . Serum estradiol level was significantly lower in the cetrorelix than in the buserelin group ( mean ± SD : 2600.58 ± 1189.11 vs. 3293.46 ± 1221.49 pg/ml , p = 0.006 ) , but the endometrial thickness was similar . The implantation rates ( 19.2 % vs. 17.7 % ) and the pregnancy rates ( 41.7 % vs. 40.0 % ) were similar between groups . The ampoules ( mean ± SD : 18.9 ± 3.0 vs. 38.9 ± 12.2 , p < 0.001 ) and injections ( mean ± SD : 6.8 ± 1.1 vs. 15.7 ± 3.1 , p < 0.001 ) of gonadotropin used were significantly lower in the cetrorelix group than in the buserelin group . No patients in either group developed a premature luteinizing hormone surge . The present study found no statistically significant difference between the two treatment modalities with regard to pregnancy rates In an attempt to improve the pregnancy rate following in vitro fertilization and embryo transfer by increasing the numbers of embryos available for transfer to each patient , a prospect i ve , r and omized comparison of clomiphene citrate alone ( 50 mg/day , cycle days 5 to 9 ) with the combination of clomiphene as above plus human menopausal gonadotropin ( 2 ampules/day , cycle days 6 , 8 , and 10 ) was undertaken from January through April 1983 , with 17 patients in each group . The combination produced increased follicular development , compared with clomiphene alone , result ing in the retrieval of more fertilizable oocytes . Two clinical pregnancies result ed in each group . These results show that a fixed combination of clomiphene and human menopausal gonadotropin produces a greater degree of enhanced follicular recruitment , result ing in the recovery of an increased number of fertilizable oocytes . The lack of a statistically significant increase in the number of embryos transferred per patient in the combination group as well as the identical number of clinical pregnancies in both groups suggests that this particular combination of clomiphene and human menopausal gonadotropin offers no advantage over the use of clomiphene alone for enhanced follicular recruitment The efficiency of IVF in unstimulated cycles was compared with that following ovarian stimulation with clomiphene citrate in a simple protocol with ultrasound monitoring only . A total of 132 couples with no previous IVF attempts , selected by female age < 35 years , indication for intracytoplasmic sperm injection or infertility caused by tubal factor or unexplained infertility were r and omized to the two protocol s. R and omization yielded two comparable groups . The clomiphene group ( 68 couples ) performed significantly better than the unstimulated group ( 64 couples ) in terms of number of cycles with oocyte harvest ( 90/111 or 81 % versus 65/114 or 57 % ; chi(2 ) = 9.21 , P < 0.002 ) , embryo transfers per started cycle ( 59/111 or 53 % versus 29/114 or 25 % ; chi(2 ) = 18.14 , P < 0.0001 ) , live intrauterine pregnancy rate per started cycle ( 20/111 or 18 % versus 4/114 or 4 % ; chi(2 ) = 12.42 , P < 0.0001 ) , live intrauterine pregnancy rate per embryo transfer ( 20/59 or 34 % versus 4/29 or 14 % ; chi(2 ) = 3.96 , P = 0.047 ) , but not in terms of implantation rate ( 22/85 or 26 % versus 4/29 or 14 % ; chi(2 ) = 1.65 ) . Only two twin pregnancies occurred . Modest side-effects were recorded following clomiphene . Accordingly , a simple clomiphene citrate protocol , but not IVF in unstimulated cycles , seems compatible with the concept of ' friendly IVF ' , yielding a fair pregnancy rate both per cycle started and per embryo transfer in selected patients . The results do not substantiate any important negative anti-oestrogenic effects of clomiphene OBJECTIVE To determine the follicular and luteal phase impact of low-dose GnRH agonist ( GnRH-a ) treatment during follicular stimulation for IVF . DESIGN A r and omized prospect i ve study compared patients receiving low-dose GnRH-a and hMG therapy to clomiphene citrate ( CC ) and hMG cycles . SETTING Patients were treated through a university-based IVF-ET program . PATIENTS Thirty-six patients underwent follicular stimulation with low-dose GnRH-a and hMG and were compared with 34 patients undergoing ovulation induction with CC and hMG . RESULTS Significantly shorter luteal phase length occurred with GnRH-a and hMG therapy ; however , there was no statistically significant difference in luteal P levels . Follicular parameters were the same ( peak E2 , number of follicles , and number of oocytes ) , suggesting that folliculogenesis was not altered . There were no statistical differences in pregnancy rates . CONCLUSIONS Sustained low-dose GnRH-a therapy during follicular stimulation does not have a clinical effect on luteal function OBJECTIVE To compare 3 stimulation protocol s in poor ovulation responders undergoing in-vitro fertilization ( IVF ) . METHODS The study was a r and omized , prospect i ve clinical trial from June 2003 to July 2004 , in Royan Institute , Tehran , Iran . One hundred and fifty-four patients , who had poor responses to ovulation induction in at least one previous IVF attempt , were r and omly divided into 3 groups . In the first group , human menopausal gonadotropin ( HMG ) was administered from day 3 of the cycle at a dose rate of 150 IU/day . In the second group , gonadotropin-releasing hormone ( GnRH ) agonist was started at a dose rate of 800 microg/day by nasal spray or 500 microg/day subcutaneously in the mid-luteal phase , followed by a st and ard HMG dose after pituitary down regulation was confirmed . In the third group , clomiphene at a dose rate of 100 mg/day was given from day 3 and HMG from day 6 . Our main outcomes were number of mature oocytes , cancellation rate , number of HMG ampoules used and incidence premature luteinizing hormone ( LH ) surge . RESULTS There was a high incidence of premature LH surge in all groups except in the GnRH group ( p=0.0001 ) and there were significant differences between groups in HMG requirements ( p=0.004 ) . There were no significant differences between groups in number of mature oocytes recovered and cancellation rate . CONCLUSION Results showed no advantage in the use of GnRH agonist compared to the older regimens of clomiphene plus HMG and HMG alone . The cancellation rate was similar for 3 protocol s and HMG requirement was higher with the use of GnRH agonist . The treatment of poor responders in assisted reproductive technologies remains a challenge The quality of ovarian stimulation for in vitro fertilization with or without an LH-RH analogue was investigated in a r and omized trial involving 30 women divided into 3 groups . Group I women were treated with the conventional clomiphene citrate-human menopausal gonadotropin combination without LH-RH analogue . Group II women ( long regimen ) received a slow-release preparation of triptorelin ( DTRp6-LH-RH ) , an LH-RH analogue , and human menopausal gonadotropin . Group II women ( short regimen ) were given triptorelin with human menopausal gonadotropin . Inhibition of the endogenous luteinizing hormone using triptorelin improved the results of in vitro fertilization in group II and group III women , but the short regimen was distinctly less compelling and less expensive than the long regimen Purpose To compare the IVF outcome of clomiphene citrate/gonadotropin/antagonist ( mild protocol ) and microdose GnRH agonist flare protocol s for poor responders undergoing in vitro fertilization . Methods 159 poor responder patients were r and omized and ovarian stimulation was performed with clomiphene citrate , gonadotropin and antagonist ( group I ) or microdose GnRH agonist flare ( group II ) protocol s. Main outcome was clinical pregnancy rate and secondary outcomes were doses of gonadotropin administration and duration of stimulation . Results There were no significant differences in age , causes of infertility , basal FSH , BMI , duration of infertility , E2 level on the day of hCG injection in both groups . Although the cancellation , fertilization , and clinical pregnancy rates were similar in both groups , the endometrial thickness , number of retrieved oocytes , mature oocytes and implantation rate were significantly higher in mild protocol . The doses of gonadotropin administration and duration of stimulation were significantly lower in mild protocol . Conclusion We recommend mild protocol in assisted reproductive technology cycles for poor responders based on our results regarding less doses of used gonadotropin and a shorter duration of stimulation A prospect i ve , r and omized , double-blind , multicentre ( n = 6 ) study was conducted to compare the influence of either a 150 or 250 IU daily fixed-dose regimen of recombinant follicle stimulating hormone ( FSH , Puregon ) on the number of oocytes retrieved and the total dose used in down-regulated women between 30 and 39 years of age undergoing ovarian stimulation . In all , 138 women were treated with recombinant FSH , 67 with 150 IU and 71 with 250 IU . The number of oocytes retrieved in the low-dose group was 9.1 compared to 10.6 in the high-dose group ( not significant ) . In the 30 - 33 years of age class receiving the 250 IU dose , a surplus of 4.2 oocytes ( 14.8 versus 10.6 ) was found , whereas in the 37 - 39 age class nearly one oocyte more was retrieved in the 150 IU group ( 8.1 versus 7.4 ) . The total dose used to reach the criterion for human chorionic gonadotrophin ( HCG ) administration was 1727 IU for the women treated with 150 IU daily and 2701 IU for the 250 IU treated women ( P < 0 . 001 ) . No significant relationships were found between serum FSH concentrations as obtained in the early follicular phase and the number of oocytes collected , or the total dose . It is concluded that in women between 30 and 39 years of age , the decline in number of oocytes retrieved with increasing age can not be overcome by augmenting the daily dose of recombinant FSH from 150 to 250 IU OBJECTIVE To compare luteal phase leuprolide acetate ( LA ) initiated pituitary down regulation followed by human menopausal gonadotropins ( hMG ) versus clomiphene citrate ( CC ) and hMG for follicular recruitment and oocyte maturation before in vitro fertilization ( IVF ) . DESIGN R and omized , prospect i ve comparison in first cycles of IVF . SETTING University Hospital , a tertiary referral center offering assisted reproductive technologies . PARTICIPANTS Participants were couples undergoing their first ever cycle of IVF and consenting to participation in the trial . RESULTS Luteal phase initiated LA/hMG was associated with a lower Output:	There was no evidence to indicate that clomiphene with gonadotropins ( with or without GnRH antagonist ) differed significantly from gonadotropins in GnRH agonist protocol s for women undergoing IVF treatment , in terms of live births or pregnancy rates . Meanwhile , use of clomiphene led to a reduction in the incidence of OHSS . Hence there was insufficient evidence to recommend use of clomiphene citrate in routine IVF practice .
MS21891	*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 test the hypothesis that homoeopathy is a placebo by examining its effect in patients with allergic rhinitis and so contest the evidence from three previous trials in this series . Design : R and omised , double blind , placebo controlled , parallel group , multicentre study . Setting : Four general practice s and a hospital ear , nose , and throat outpatient department . Participants : 51 patients with perennial allergic rhinitis . Intervention : R and om assignment to an oral 30c homoeopathic preparation of principal inhalant allergen or to placebo . Main outcome measures : Changes from baseline in nasal inspiratory peak flow and symptom visual analogue scale score over third and fourth weeks after r and omisation . Results : Fifty patients completed the study . The homoeopathy group had a significant objective improvement in nasal airflow compared with the placebo group ( mean difference 19.8 l/min , 95 % confidence interval 10.4 to 29.1 , P=0.0001 ) . Both groups reported improvement in symptoms , with patients taking homoeopathy reporting more improvement in all but one of the centres , which had more patients with aggravations . On average no significant difference between the groups was seen on visual analogue scale scores . Initial aggravations of rhinitis symptoms were more common with homoeopathy than placebo ( 7 ( 30 % ) v 2 ( 7 % ) , P=0.04 ) . Addition of these results to those of three previous trials ( n=253 ) showed a mean symptom reduction on visual analogue scores of 28 % ( 10.9 mm ) for homoeopathy compared with 3 % ( 1.1 mm ) for placebo ( 95 % confidence interval 4.2 to 15.4 , P=0.0007 ) . Conclusion : The objective results reinforce earlier evidence that homoeopathic dilutions differ from placebo Little is known about long-term effects of homeopathic treatment . Following a double-blind , placebo controlled trial of classical homeopathy in chronic headaches , we conducted a 1-year observational study of 18 patients following the double-blind phase , and a complete follow-up study of all trial participants . Eighteen patients received free treatment for daily diary data ( frequency , intensity , duration of headaches ) over the course of 1 y. All patients enrolled in the double-blind study were sent a 6-week headache diary , a follow-up question naire , a personality inventory and a complaint list . Eighty-seven , of the original 98 patients enrolled returned question naires , 81 returned diaries . There was no additional change from the end of the trial to the one-year follow-up . The improvement seen at the end of the 12-week trial was stable after 1 y. No differential effects according to treatment after the trial could be seen . Patients with no treatment following the trial had the most improvement after 1 y. Five of 18 patients can be counted responders according to ARIMA analysis of single-case time-series . Patients with double diagnoses and longer treatment duration tended to have clearer improvements than the rest of the patients . Approximately 30 % of patients in homeopathic treatment will benefit after 1 y of treatment . There is no indication of a specific , or of a delayed effect of homeopathy Abstract Objective : To evaluate the efficacy of homoeopathic immunotherapy on lung function and respiratory symptoms in asthmatic people allergic to house dust mite . Design : Double blind r and omised controlled trial . Setting : 38 general practice s in Hampshire and Dorset . Participants : 242 people with asthma and positive results to skin prick test for house dust mite ; 202 completed clinic based assessment s , and 186 completed diary based assessment s. Intervention : After a four week baseline assessment , participants were r and omised to receive oral homoeopathic immunotherapy or placebo and then assessed over 16 weeks with three clinic visits and diary assessment s every other week . Outcome measure : Clinic based assessment s : forced expiratory volume in one second ( FEV1 ) , quality of life , and mood . Diary based assessment s : morning and evening peak expiratory flow , visual analogue scale of severity of asthma , quality of life , and daily mood . Results : There was no difference in most outcomes between placebo and homoeopathic immunotherapy . There was a different pattern of change over the trial for three of the diary assessment s : morning peak expiratory flow ( P=0.025 ) , visual analogue scale ( P=0.017 ) , and mood ( P=0.035 ) . At week three there was significant deterioration for visual analogue scale ( P=0.047 ) and mood ( P=0.013 ) in the homoeopathic immunotherapy group compared with the placebo group . Any improvement in participants ' asthma was independent of belief in complementary medicine . Conclusion : Homoeopathic immunotherapy is not effective in the treatment of patients with asthma . The different patterns of change between homoeopathic immunotherapy and placebo over the course of the study are unexplained BACKGROUND The use of antibiotics in the initial treatment of acute otitis media is currently being question ed . Homeopathy has been used historically to treat this illness , but there have been no method ologically rigorous trials to determine whether there is a positive treatment effect . METHODS A r and omized double blind placebo control pilot study was conducted in a private pediatric practice in Seattle , WA . Seventy-five children ages 18 months to 6 years with middle ear effusion and ear pain and /or fever for no more than 36 h were entered into the study . Children received either an individualized homeopathic medicine or a placebo administered orally three times daily for 5 days , or until symptoms subsided , whichever occurred first . Outcome measures included the number of treatment failures after 5 days , 2 weeks and 6 weeks . Diary symptom scores during the first 3 days and middle ear effusion at 2 and 6 weeks after treatment were also evaluated . RESULTS There were fewer treatment failures in the group receiving homeopathy after 5 days , 2 weeks and 6 weeks , with differences of 11.4 , 18.4 and 19.9 % , respectively , but these differences were not statistically significant . Diary scores showed a significant decrease in symptoms at 24 and 64 h after treatment in favor of homeopathy ( P < 0.05 ) . Sample size calculations indicate that 243 children in each of 2 groups would be needed for significant results , based on 5-day failure rates . CONCLUSIONS These results suggest that a positive treatment effect of homeopathy when compared with placebo in acute otitis media can not be excluded and that a larger study is justified Homeopathy is often advocated as a prophylaxis of migraine and headaches . The aim of this systematic review was to evaluate the clinical trials , testing the efficacy of homeopathy for these indications . Independent computerized literature search es were carried out in 4 data bases . Only r and omized , placebo-controlled trials were included . Four such studies were found . Their method ological quality was variable but , on average , satisfactory . One study suggested that homeopathic remedies were effective . The other , method ologically stronger trials did not support this notion . It is concluded that the trial data available to date do not suggest that homeopathy is effective in the prophylaxis of migraine or headache beyond a placebo effect BACKGROUND Stomatitis is a common consequence of chemotherapy and a condition for which there is little effective treatment . Although the management of patients with other chemotherapy-related toxicities has improved in recent years , the incidence of stomatitis is increasing because of more intensive treatment and is often a dose limiting factor in chemotherapy . The authors assessed the efficacy of a homeopathic remedy , TRAUMEEL S(R ) , in the management of chemotherapy-induced stomatitis in children undergoing bone marrow transplantation . METHODS A r and omized , placebo-controlled , double-blind clinical trial was conducted in 32 patients ages 3 - 25 years who had undergone allogeneic ( 16 patients ) or autologous ( 16 patients ) stem cell transplantation . Of the 30 evaluable patients , 15 were assigned placebo , and 15 were assigned TRAUMEEL S both as a mouth rinse , administered five times daily from 2 days after transplantation for a minimum of 14 days , or until at least 2 days after all signs of stomatitis were absent . Stomatitis scores were evaluated according to the World Health Organization grading system for mucositis . RESULTS A total of five patients ( 33 % ) in the TRAUMEEL S treatment group did not develop stomatitis compared with only one patient ( 7 % ) in the placebo group . Stomatitis worsened in only 7 patients ( 47 % ) in the TRAUMEEL S treatment group compared with 14 patients ( 93 % ) in the placebo group . The mean area under the curve stomatitis scores were 10.4 in the TRAUMEEL S treatment group and 24.3 in the placebo group . This difference was statistically significant ( P < 0.01 ) . CONCLUSIONS This study indicates that TRAUMEEL S may reduce significantly the severity and duration of chemotherapy-induced stomatitis in children undergoing bone marrow transplantation BACKGROUND Recent meta-analyses of r and omized controlled trials in homeopathy have suggested that homeopathy is more than a placebo response . OBJECTIVE Comparison of the effectiveness of homeopathy in primary care with conventional medicine in primary care for three commonly encountered clinical conditions . DESIGN An international multicenter , prospect i ve , observational study in a real world medical setting comparing the effectiveness of homeopathy with conventional medicine . PARTICIPANTS Thirty ( 30 ) investigators with conventional medical licenses at six clinical sites in four countries enrolled 500 consecutive patients with at least one of the following three complaints : ( 1 ) upper respiratory tract complaints including allergies ; ( 2 ) lower respiratory tract complaints including allergies ; or ( 3 ) ear complaints . MAIN OUTCOME MEASURES The primary outcomes criterion was the response to treatment , defined as cured or major improvement after 14 days of treatment . Secondary outcomes criteria were : ( 1 ) rate of recovery ; ( 2 ) occurrence of adverse events ; ( 3 ) patient satisfaction ; and ( 4 ) length of consultation . RESULTS Four hundred and fifty-six ( 456 ) patient visits were compared : 281 received homeopathy , 175 received conventional medicine . The response to treatment as measured by the primary outcomes criterion for patients receiving homeopathy was 82.6 % , for conventional medicine it was 68 % . Improvement in less than 1 day and in 1 to 3 days was noted in 67.3 % of the group receiving homeopathy and in 56.6 % of those receiving conventional medicine . The adverse events for those treated with conventional medicine was 22.3 % versus 7.8 % for those treated with homeopathy . Seventy-nine percent ( 79.0 % ) of patients treated with homeopathy were very satisfied and 65.1 % of patients treated with conventional , medicine were very satisfied . In both treatment groups 60 % of cases had consultations lasting between 5 and 15 minutes . CONCLUSIONS Homeopathy appeared to be at least as effective as conventional medical care in the treatment of patients with the three conditions studied Output:	Collectively they failed to provide strong evidence in favour of homeopathy . In particular , there was no condition which responds convincingly better to homeopathic treatment than to placebo or other control interventions . Similarly , there was no homeopathic remedy that was demonstrated to yield clinical effects that are convincingly different from placebo . It is concluded that the best clinical evidence for homeopathy available to date does not warrant positive recommendations for its use in clinical practice
MS21892	*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 no-reflow phenomenon is associated with poor functional and clinical outcomes for patients with acute myocardial infa rct ion ( AMI ) . In the era of primary intervention , accurately identifying lesions at high risk of no reflow is of crucial importance . At present , no study into the relationship between lesion morphology and no reflow has been performed . The aim of this study was to investigate the relationship between preintervention intravascular ultrasound ( IVUS ) lesion morphology and the no-reflow phenomenon . Methods and Results —This study comprised 100 consecutive patients with AMI who underwent preintervention IVUS and were successfully recanalized with primary balloon angioplasty or stenting . IVUS was again performed to identify and exclude any mechanical vessel obstruction in cases of thrombolysis in myocardial infa rct ion flow grade 0 , 1 , or 2 after intervention in the absence of angiographic stenosis . Angiographic no reflow was seen in 13 patients ( 13 % ) . Univariate analysis indicated that hypercholesterolemia , fissure and dissection , lipid pool – like image , lesion , and reference external elastic membrane cross-sectional area correlate with the no-reflow phenomenon . Multivariate logistic regression analysis showed that lipid pool – like image ( P < 0.05 ; odds ratio 118 ; 95 % CI , 1.28 to 11 008 ) and lesion elastic membrane cross-sectional area ( P < 0.05 ; odds ratio 1.55 ; 95 % CI 1.01 to 2.38 ) are independent predictive factors of no-reflow phenomenon after reperfusion for AMI . Conclusions —Large vessels with lipid pool – like image are at high risk for no reflow after primary intervention for AMI . Also , plaque content may play a role in damage to the microcirculation after primary intervention for AMI OBJECTIVES The aim of this study was to underst and the impact of attenuated plaque on distal embolization during stent implantation in patients with acute myocardial infa rct ion ( AMI ) . BACKGROUND Attenuated plaques identified by grayscale intravascular ultrasound ( IVUS ) might predict transient deterioration in coronary flow and /or no-reflow during percutaneous coronary intervention ( PCI ) . METHODS We analyzed clinical , angiographic , and IVUS data from 364 patients ( n = 364 infa rct -related arteries ) enrolled in the r and omized HORIZONS-AMI ( Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infa rct ion ) trial . No-reflow was final Thrombolysis In Myocardial Infa rct ion ( TIMI ) flow grade ≤2 in the absence of mechanical obstruction . Attenuated plaque was hypoechoic or mixed atheroma with ultrasound attenuation without calcification . A mean attenuation score was created by measuring the angle of attenuation each 1 mm , scoring the angle as 1 to 4 ( corresponding to < 90 ° , 90 ° to 180 ° , 180 ° to 270 ° , or 270 ° to 360 ° , respectively ) , summing the scores , and normalizing for analysis length . RESULTS Overall , 284 ( 78.0 % ) patients had attenuated plaques ; no-reflow occurred in 37 ( 10.2 % ) . Patients with no-reflow had a higher mean attenuation score ( median [ interquartile range ] 2.2 [ 0.0 to 2.8 ] vs. 1.3 [ 0.7 to 1.8 ] , p < 0.001 ) , lower baseline left ventricular ejection fraction ( 52.8 % [ 43.2 % to 61.5 % ] vs. 61.4 % [ 52.2 % to 68.1 % ] , p = 0.002 ) , and more baseline angiographic thrombus ( 89.2 % vs. 74.1 % , p = 0.043 ) with no differences in post-PCI stent expansion versus patients without no-reflow . Multivariate analysis indicated that mean attenuation score was the strongest predictor of no-reflow . The mean attenuation score that best predicted no-reflow was ≥2 points ( 90 ° to 180 ° , sensitivity of 81.5 % , and specificity of 80.5 % ) . CONCLUSIONS Attenuated plaque was present in three-quarters of patients with AMI . The amount of attenuated plaque strongly correlated with no-reflow ; the larger the attenuated plaque , the greater the likelihood of no-reflow . ( Dual Arm Factorial R and omized Trial in Patients w/ST Segment Elevation AMI to Compare the Results of Using Anticoagulation With Either Unfractionated Heparin + Routine GP IIb/IIIa Inhibition or Bivalirudin + Bail-out GP IIb/IIIa Inhibition ; and Primary Angioplasty with stent implantation with Either a Slow Rate-release Paclitaxel-eluting Stent [ TAXUS ™ ] or Uncoated Bare Metal Stent [ EXPRESS2 ™ ] ; NCT00433966 ) OBJECTIVES We aim ed to predict the high-risk plaque of distal embolization after stent deployment in patients with acute ST-segment elevation myocardial infa rct ion ( STEMI ) with Virtual Histology intravascular ultrasound ( VH-IVUS ) ( Volcano Therapeutics , Inc. , Rancho Cordova , California ) . BACKGROUND Distal embolization during primary percutaneous coronary intervention ( PCI ) carries a poor prognosis in patients with STEMI . However , it is unclear which plaque characteristics cause distal embolization after stent deployment . METHODS A total of 71 patients with STEMI were included prospect ively . All patients underwent primary PCI within 12 h of symptom onset . After crossing the lesion with a guidewire and performing thrombectomy with an aspiration catheter , VH-IVUS of the infa rct -related vessel was performed . Stent deployment was then undertaken without embolic protection . ST-segment re-elevation ( STR ) was used to evaluate distal embolization . Correlations among plaque characteristics , morphology , and distal embolization were analyzed . RESULTS The STR after stent deployment was observed in 11 patients ( STR group , 15.5 % ) . Necrotic core volume was significantly higher in the STR group than in the non-STR group ( 32.9 + /- 14.1 mm3 vs. 20.4 + /- 19.1 mm3 , p < 0.05 ) . Total plaque volume was similar in both groups . On receiver-operating characteristic analysis , necrotic core volume clearly predicted STR after stent deployment as compared with fibrous , fibro-lipid , dense calcium , and total plaque volumes . The necrotic core volume that was best predictive for STR was 33.4 mm3 , with a sensitivity of 81.7 % and a specificity of 63.6 % . CONCLUSIONS Virtual Histology IVUS is a useful means of predicting the risk of distal embolization after primary stent deployment in patients with STEMI OBJECTIVES We evaluated the clinical significance of attenuated plaque ( hypoechoic plaque with deep ultrasound attenuation ) . BACKGROUND Attenuated plaques are unusual intravascular ultrasound ( IVUS ) findings in patients with acute coronary syndrome ( ACS ) . METHODS We review ed clinical presentations and angiographic and pre-intervention IVUS findings in 293 ACS patients undergoing percutaneous coronary intervention ( PCI ) without a distal protection device : 187 with non-ST-segment elevation myocardial infa rct ion ( NSTEMI ) and 106 with ST-segment elevation myocardial infa rct ion ( STEMI ) . RESULTS Attenuated plaque was observed in 75 patients ( 25.6 % ) : 39.6 % of STEMI versus 17.6 % of NSTEMI ( p < 0.001 ) . ( We also review ed 100 r and omly selected patients with stable angina and pre-intervention IVUS ; none had attenuated plaque . ) Overall , in ACS patients with attenuated plaques : 1 ) the level of C-reactive protein was higher ; 2 ) angiographic thrombus and initial coronary flow Thrombolysis In Myocardial Infa rct ion flow grade < 2 were more common ; and 3 ) IVUS lesion site plaque burden and remodeling index were significantly greater , lesion site luminal dimensions significantly smaller , and thrombus , positive remodeling , and plaque rupture were more common . No-reflow ( 26.7 % vs. 4.6 % , p < 0.001 ) and deteriorated post-PCI coronary blood flow ( 8.0 % vs. 2.8 % , p = 0.001 ) were higher . In ACS patients with normal coronary blood flow at baseline , deterioration in the coronary blood flow post-PCI was more common in lesions with attenuated plaque . CONCLUSIONS Attenuated plaque was more common in ACS patients with STEMI than NSTEMI . Attenuated plaque in ACS patients was associated with a higher C-reactive protein level , more severe and complex lesion morphology , reduced coronary blood flow before PCI , and especially no-reflow after PCI BACKGROUND Atherosclerotic plaques that lead to acute coronary syndromes often occur at sites of angiographically mild coronary-artery stenosis . Lesion-related risk factors for such events are poorly understood . METHODS In a prospect i ve study , 697 patients with acute coronary syndromes underwent three-vessel coronary angiography and gray-scale and radiofrequency intravascular ultrasonographic imaging after percutaneous coronary intervention . Subsequent major adverse cardiovascular events ( death from cardiac causes , cardiac arrest , myocardial infa rct ion , or rehospitalization due to unstable or progressive angina ) were adjudicated to be related to either originally treated ( culprit ) lesions or untreated ( nonculprit ) lesions . The median follow-up period was 3.4 years . RESULTS The 3-year cumulative rate of major adverse cardiovascular events was 20.4 % . Events were adjudicated to be related to culprit lesions in 12.9 % of patients and to nonculprit lesions in 11.6 % . Most nonculprit lesions responsible for follow-up events were angiographically mild at baseline ( mean [ ±SD ] diameter stenosis , 32.3±20.6 % ) . However , on multivariate analysis , nonculprit lesions associated with recurrent events were more likely than those not associated with recurrent events to be characterized by a plaque burden of 70 % or greater ( hazard ratio , 5.03 ; 95 % confidence interval [ CI ] , 2.51 to 10.11 ; P<0.001 ) or a minimal luminal area of 4.0 mm(2 ) or less ( hazard ratio , 3.21 ; 95 % CI , 1.61 to 6.42 ; P=0.001 ) or to be classified on the basis of radiofrequency intravascular ultrasonography as thin-cap fibroatheromas ( hazard ratio , 3.35 ; 95 % CI , 1.77 to 6.36 ; P<0.001 ) . CONCLUSIONS In patients who presented with an acute coronary syndrome and underwent percutaneous coronary intervention , major adverse cardiovascular events occurring during follow-up were equally attributable to recurrence at the site of culprit lesions and to nonculprit lesions . Although nonculprit lesions that were responsible for unanticipated events were frequently angiographically mild , most were thin-cap fibroatheromas or were characterized by a large plaque burden , a small luminal area , or some combination of these characteristics , as determined by gray-scale and radiofrequency intravascular ultrasonography . ( Funded by Abbott Vascular and Volcano ; Clinical Trials.gov number , NCT00180466 . ) OBJECTIVES We investigated attenuated plaque ( hypoechoic plaque with deep ultrasonic attenuation despite absence of bright calcium ) in nonculprit lesions . BACKGROUND Recent intravascular ultrasound ( IVUS ) studies describe acoustic shadowing behind large , echolucent , acute culprit lesion sites in the absence of bright calcium . Such " attenuated plaque " is considered a characteristic of high-risk lesions , but its prevalence in stable nonculprit lesions is incompletely known . METHODS We review ed IVUS pullback data from nonculprit vessels in 159 patients from the ASTEROID ( A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound-Derived Coronary Atheroma Burden ) trial . We identified attenuated plaque and compared volumetric IVUS data in the segments with and without attenuation . In addition , we described plaque morphology in segments with attenuation at baseline and follow-up . RESULTS Attenuated plaque was found in 17 of 159 patients ( 10.7 % , 95 % confidence interval : 6 % to 17 % ) . At baseline , there were no significant differences in clinical presentation and cardiovascular risk factors between patients with and without attenuation . Other than a greater plaque eccentricity index ( p = 0.008 ) , Output:	Our study presents the evidence that plaque with ultrasound signal attenuation would induce slow/no reflow phenomenon and distal embolization during PCI , but this appearance has no impact on MACE rates within three years
MS21893	*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 examined how two types of public education programs influenced how the public perceived persons with mental illness , their potential for violence , and the stigma of mental illness . A total of 161 participants were r and omly assigned to one of three programs : one that aim ed to combat stigma , one that highlighted the association between violence and psychiatric disorders , and a control group . Participants who completed the education-about-violence program were significantly more likely to report attitudes related to fear and dangerousness , to endorse services that coerced persons into treatment and treated them in segregated areas , to avoid persons with mental illness in social situations , and to be reluctant to help persons with mental illness Background : Studies regarding the effectiveness of CME programmes on physicians ’ behaviour and communication skills showed inconsistent results . Few r and omized controlled trials have been conducted in Asia . Methods : To evaluate the effectiveness of a 4 2-hour education programme to improve GP interviewing behaviours , 16 general practitioners were r and omized to the intervention and control groups , respectively . Physicians assigned to the intervention group received 8 hours of training emphasizing interviewing behaviours in the diagnosis and treatment of depression and generalized anxiety disorders ( GDS ) . Those assigned to the control group did not receive any training until the completion of study . St and ardized patients were used to evaluate the performance of physicians . Two consultations before and after enrolling in the education programme were videotaped . Independent evaluations of consultations were made by a trained clinical psychologist and a social worker blinded to the study status of physicians . The rating schedule for the videotapes was based on the tasks listed on the Calgary Cambridge Observation Guide . Results : The change of score between the intervention and control physicians was significantly different in ‘ active listening and facilitating patients ’ response ’ ( p = 0.011 ) with the intervention physicians having improvement of score . For ‘ non-verbals ’ , ‘ underst and ing patient 's perspective ’ and ‘ negotiating mutual plan of action ’ , positive change of score in the intervention physicians were seen when compared to that of the control , although the difference did not reach statistical significance ( p = 0.06 , p = 0.05 , p = 0.06 , respectively ) . However , for ‘ opening ’ , ‘ structuring the consultation ’ , ‘ explanation and planning ’ and ‘ closure ’ , there were no statistical significant differences between control and intervention group . Conclusions : Our results showed that only certain communication skills , such as active listening and facilitating patient 's response , can be taught in the management of depression and generalized anxiety disorder ( GAD ) in Chinese primary care physicians This study examines the personal and attitudinal variables that are associated with helping behavior in a hypothetical general practice setting . We explored the effect of an antistigma seminar during a psychiatric clerkship on medical students ’ attitudes toward the mentally ill . We r and omly assigned three rotations of students ( 81 students ) to receive the seminar and three rotations ( 85 students ) as controls . The students expressed views about patients with schizophrenia or depressive disorder portrayed in video vignettes . How dangerous the students perceived target individuals to be was the major determinant of helping behavior . The students ’ gender , religious affiliation , affective reaction , skill assessment , and controllability attribution were less consistent in predicting behavior . Exposure to the seminar and clerkship experience significantly improved attitudes , but attributes of responsibility and readiness to provide medical care for psychiatric patients were the most resistant to change . We identified certain issues that should be highlighted in future antistigma programs Stigmatizing , or discriminatory , perspectives and behaviour , which target individuals on the basis of their mental health , are observed in even the youngest school children . We conducted a systematic review of the published and unpublished , scientific literature concerning the benefits and harms of school-based interventions , which were directed at students 18 years of age or younger to prevent or eliminate such stigmatization . Forty relevant studies were identified , yet only a qualitative synthesis was deemed appropriate . Five limitations within the evidence base constituted barriers to drawing conclusive inferences about the effectiveness and harms of school-based interventions : poor reporting quality , a dearth of r and omized controlled trial evidence , poor methods quality for all research design s , considerable clinical heterogeneity , and inconsistent or null results . Nevertheless , certain suggestive evidence derived both from within and beyond our evidence base has allowed us to recommend the development , implementation and evaluation of a curriculum , which fosters the development of empathy and , in turn , an orientation toward social inclusion and inclusiveness . These effects may be achieved largely by bringing especially but not exclusively the youngest children into direct , structured contact with an infant , and likely only the oldest children and youth into direct contact with individuals experiencing mental health difficulties . The possible value of using educational activities , material s and contents to enhance hypothesized benefits accruing to direct contact also requires investigation . Overall , the curriculum might serve as primary prevention for some students and as secondary prevention for others Background A Mental Health First Aid course has been developed which trains members of the public in how to give initial help in mental health crisis situations and to support people developing mental health problems . This course has previously been evaluated in a r and omized controlled trial in a workplace setting and found to produce a number of positive effects . However , this was an efficacy trial under relatively ideal conditions . Here we report the results of an effectiveness trial in which the course is given under more typical conditions . Methods The course was taught to members of the public in a large rural area in Australia by staff of an area health service . The 16 Local Government Areas that made up the area were grouped into pairs matched for size , geography and socio-economic level . One of each Local Government Area pair was r and omised to receive immediate training while one served as a wait-list control . There were 753 participants in the trial : 416 in the 8 trained areas and 337 in the 8 control areas . Outcomes measured before the course started and 4 months after it ended were knowledge of mental disorders , confidence in providing help , actual help provided , and social distance towards people with mental disorders . The data were analysed taking account of the clustered design and using an intention-to-treat approach . Results Training was found to produce significantly greater recognition of the disorders , increased agreement with health professionals about which interventions are likely to be helpful , decreased social distance , increased confidence in providing help to others , and an increase in help actually provided . There was no change in the number of people with mental health problems that trainees had contact with nor in the percentage advising someone to seek professional help . Conclusions Mental Health First Aid training produces positive changes in knowledge , attitudes and behaviour when the course is given to members of the public by instructors from the local health service BACKGROUND AND OBJECTIVES Although many studies have investigated the impact of causal models on public attitudes toward people with psychosis , the effect of causal models on patients with psychosis is unclear . Clinicians must therefore decide about providing causal information without knowing how it will impact on patient and treatment . This study investigates the effect of causal models on different aspects of treatment motivation . METHODS In an experimental online study healthy individuals ( n = 461 ) were instructed to imagine experiencing psychotic symptoms and seeking professional help . The imagination was supported by an audio play cover story . Subsequently , participants were r and omized to four conditions differing in the content of the causal model given for the occurring symptoms ( biological , psychological , combined and no causal explanation ) . RESULTS Different causal models impacted on different aspects of treatment motivation : Participants who had received a biological causal model showed high willingness to take medication , whereas participants who had received a psychological model reported high perceived personal control over symptoms . Participants who had received a causal model that combined biological and psychological aspects reported high acceptance of medication and high motivation to undergo treatment by this clinician . CONCLUSIONS The results underline the impact the content of a causal model may have on patients ' treatment motivation and - as a consequence - on treatment success . Overall , the integration of psychological and biological aspects within a causal model seems most promising in terms of adherence to various types of treatment This study attempted to determine the effects of a direct-mail campaign on the attitudes of managers and presidents of industries toward the mentally retarded . The participants in the study were 99 managers and presidents selected from a total population of 4290 within the State of Alabama , USA . R and om sampling techniques were utilized to select and assign managers and presidents into an experimental group ( n = 50 ) and a control group ( n = 49 ) , giving a total usable sample size of 99 . The size of this sample was adequate to insure that , in 19 out of 20 cases , the sample mean was within 0.50 points of the population mean on the response scale according to Elliot ( 1980 ) . The pre-test of the attitude scale was administered to the experimental and control groups by mail . A post-test was administered to the control and experimental groups one week after the mailing of the final pamphlet . The major finding of this study revealed positive attitude gains from pre-test to post-test for the experimental group following the direct-mail campaign . No significant difference was noted for the control group from pre-test and post-test . Pre-test scores of the experimental and control groups were not significantly different ; however , post-test scores between these groups were significantly different . The results of this research contribute further information on a direct-mail approach for changing attitudes of managers and presidents of industries toward mentally retarded persons OBJECTIVES The authors used nationwide survey data to characterize current public conceptions related to recognition of mental illness and perceived causes , dangerousness , and desired social distance . METHODS Data were derived from a vignette experiment included in the 1996 General Social Survey . Respondents ( n = 1444 ) were r and omly assigned to 1 of 5 vignette conditions . Four vignettes described psychiatric disorders meeting diagnostic criteria , and the fifth depicted a " troubled person " with sub clinical problems and worries . RESULTS Results indicate that the majority of the public identifies schizophrenia ( 88 % ) and major depression ( 69 % ) as mental illnesses and that most report multicausal explanations combining stressful circumstances with biologic and genetic factors . Results also show , however , that smaller proportions associate alcohol ( 49 % ) or drug ( 44 % ) abuse with mental illness and that symptoms of mental illness remain strongly connected with public fears about potential violence and with a desire for limited social interaction . CONCLUSIONS While there is reason for optimism in the public 's recognition of mental illness and causal attributions , a strong stereotype of dangerousness and desire for social distance persist . These latter conceptions are likely to negatively affect people with mental illness Authors examined the combined effects of descriptive and explanatory information on peers ' perceptions and behavioral intentions toward an unfamiliar child with autism . Children ( N = 576 ; M age = 10.06 ) were r and omly assigned to view two videotapes of a boy engaging in typical and autistic behaviors receiving either descriptive ( AUT-D ) or descriptive and explanatory information ( AUT-D + E ) . Children responded to measures of attitudes ( Adjective Checklist ) and behavioral intentions ( Shared Activities Question naire ) . Children rated the typical boy more favorably than the boy showing autistic symptoms . When compared to descriptive information alone , the combination of descriptive and explanatory information result ed in improved third- and fourth- grade rs ' but not fifth- grade rs ' attitudes toward the child with autism . Combined information improved behavioral intentions across grade s ; however , girls ( vs. boys ) were more responsive to information as evidence d by differences in academic intentions . The combination of descriptive and explanatory information about autism appears to have a positive effect on children 's attitudes and behavioral intentions . Implication s of the findings are briefly discussed as well as study limitations and recommendations for future research BACKGROUND Direct social contact interventions are known to reduce mental health stigma . Filmed social contact may be equally effective and have practical and cost advantages . AIMS To compare the effectiveness of a DVD , a live intervention and a lecture control , in reducing stigma , testing the hypotheses that : ( a ) DVD and live interventions will be equally effective ; and ( b ) the interventions with social contact ( DVD/live ) will be more effective than the lecture . Cost-effectiveness , process and acceptability are also assessed . METHOD Student nurses were r and omised to : ( a ) watch a DVD of service users/informal carers talking about their experiences , ( b ) watch a similar live presentation , or ( c ) attend a lecture . Primary outcomes were changes in attitudes ( using the Mental Illness : Clinicians Attitudes Scale , MICA ) , emotional reactions ( using the Emotional Reactions to Mental Illness Scale , ERMIS ) , intended proximity ( using the Reported and Intended Behaviour Scale , RIBS ) , and knowledge ( using the Social Contact Intended Learning Outcomes , SCILO ) , immediately after the intervention and at 4-month follow-up . RESULTS For the 216 participants , there were no differences between the DVD and live groups on MICA , ERMIS or RIBS scores . The DVD group had higher SCILO ( knowledge ) scores . The combined social contact group ( DVD/live ) had better MICA and RIBS scores than the lecture group , the latter difference maintained at 4 months . The DVD was the most cost-effective of the interventions , and the live session the most popular . CONCLUSIONS Our hypotheses were confirmed . This study supports the wider use of filmed social contact interventions to reduce stigma about mental illness The issue of suicide warning signs on the Internet is considered . In addition to review ing some of the relevant conceptual issues about warning signs , a r and om sample of Internet sites was selected and review ed . Warning signs were grouped and agreement across sites was examined , with results confirming broad disparity in what is presented to the public . The implication s of a lack of consensus on warning signs for suicide are discussed Acceptance and commitment therapy ( ACT ) has previously been shown to alter stigmatizing attitudes and to be relatively useful for psychologically inflexible participants . The present study is the first to bring those two findings together by comparing ACT to an education intervention for reducing stigma toward people with psychological disorders , and examining whether results differ for psychologically inflexible versus flexible individuals . A sample of college students ( N = 95 ) was r and omly assigned to a 2(1)2h ACT or educational workshop . Measures were taken before and after the workshop and at a 1-month follow- Output:	The median SMDs indicate that mass media interventions may have a small to medium effect in decreasing prejudice , and are equivalent to reducing the level of prejudice from that associated with schizophrenia to that associated with major depression . AUTHORS ' CONCLUSIONS Mass media interventions may reduce prejudice , but there is insufficient evidence to determine their effects on discrimination .
MS21894	*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 this study , our prospect i ve experience with a multimodal follow-up protocol is summarized , with special emphasis on predicting the treatment outcome of cervical diseases . MATERIAL S AND METHODS Liquid-based cytology sample s ( ThinPrep ) from 209 women exhibiting the whole spectrum of human papilloma virus (HPV)-related cervical diseases were investigated by cytology , PCR-based HPV genotyping and DNA cytometry pre-surgery . The first control cytology and type-specific HPV tests were performed at 3 months post-surgery . RESULTS The success rate of surgery was 95 % in eradicating high- grade cervical disease and 90 % in eliminating the baseline HPV genotype . Treatment failure was significantly correlated with baseline cytology ( p=0.011 ) , resection margin status ( p=0.016 ) and HPV positivity at 3 months post-surgery ( p=0.04 ) . Multivariate logistic regression analysis showed that type-specific persistent HPV infection ( p=0.028 ) , baseline cytology ( p=0.039 ) and histology ( p=0.065 ) were independent predictors of residual cervical neoplasias . CONCLUSION Our results showed that our multimodal surveillance protocol may help to individually assess the anticipated clinical outcome of cervical diseases post-surgery Cervical intraepithelial neoplasia 3 ( CIN3 ) is the precursor of mostsquamous carcinomas and serves as a surrogate end point . However , small CIN3 lesions are rarely associated with concurrent invasion . We hypothesized that aggressive follow-up for cytology of atypical squamous cells of undetermined significance ( ASCUS ) or low- grade squamous intraepithelial lesion ( LSIL ) leads predominantly to detection of smaller CIN3 lesions than those usually associated with cancer . We assessed this hypothesis in a masked histopathologic review of 330 CIN3 lesions in the ASCUS LSILTriage Study , focusing on ASCUS referrals . ASCUS referrals underwent r and omized management [ colposcopy for repeat cytology of high- grade squamous intraepithelial lesion ( HSIL ) , colposcopy for oncogenic human papillomavirus ( HPV ) detection or repeat HSIL , or immediate colposcopy ] ; then all were followed with repeat cytology for 2 years , followed by colposcopy and aggressive treatment . We assessed all CIN3 lesions qualitatively and measured 39 of them . CIN3 lesions were overwhelmingly small . Compared with enrollment , lesions found at follow-up or exit involved fewer tissue fragments ( P < 0.01 ) and showed less diffuse gl and involvement ( P = 0.03 ) . CIN3 lesions found postenrollment after HPV testing involved the fewest tissue fragments [ versus immediate colposcopy ( P = 0.04 ) or repeat cytology of HSIL ( P = 0.02 ) ] , and none showed diffuse gl and involvement . The median distal-proximal length was 6.5 mm ( median replacement of total epithelium = 5 % ) in the 39 measured cases . We conclude that CIN3 lesions underlying ASCUS or LSIL generally lack features associated with invasion , particularly if managed using HPV testing , suggesting that aggressive management leads to early detection of CIN3 but probably prevents relatively few cancers in screened population OBJECTIVE To evaluate testing for high-risk human papillomavirus ( HR HPV ) E6/E7 mRNA transcripts 6 months after conisation for cervical intraepithelial neoplasia grade 2 or worse ( CIN2 + ) to determine the risk of residual CIN2 + . METHODS We prospect ively followed 344 women treated for CIN2 + by conisation . HR HPV mRNA testing ( PreTect HPV-Proofer , NorChip ® ) , HR HPV DNA testing ( AMPLICOR HPV Test , Roche Diagnostics ® ) and cytology was performed at 6 and 12 months after conisation . Biopsies were taken within 18 months of conisation if indicated by abnormal cytology , abnormal colposcopy , or positive HPV test . The LINEAR ARRAY HPV Genotyping Test ( Roche Diagnostics ® ) was used to genotype cases with histologically confirmed residual disease diagnosed within 18 months after conisation . RESULTS 6.4 % ( 22/344 ) of study women had detected residual CIN2 + . They were significantly older than those without residual CIN2 + ( 43.2 and 37.2 years respectively , p<0.001 ) . Among women with detected residual CIN2 + , 54.5 % ( 12/22 ) had positive resection margins , 63.6 % ( 14/22 ) had abnormal cytology , and 95.5 % ( 21/22 ) had a positive HR HPV DNA test at 6 months . Sensitivity of HR HPV mRNA testing was 45.5 % ( 95 % confidence interval : 26.8 - 65.5 % ) at 6 months to predict detected residual CIN2 + . Eight of 12 women who were HR HPV mRNA-negative at 6 months were HR HPV DNA-positive for one of the HPV types included in the mRNA test . CONCLUSION Detection of E6/E7 mRNA transcripts by PreTect HPV Proofer does not seem suitable for short-term follow-up to detect residual CIN2 + after conisation OBJECTIVE : To estimate the effectiveness of the human papillomavirus ( HPV ) test performed after conization in predicting residual disease in patients who subsequently underwent hysterectomy . METHODS : A total of 115 patients who underwent hysterectomy after conization caused by cervical intraepithelial neoplasia grade 3 ( CIN 3 ) and microinvasive cervical cancer ( IA1 cancer ) were included in this prospect i ve study . All patients underwent HPV testing with a liquid hybridization assay immediately before hysterectomy . Differences in sensitivity , specificity , and accuracy between resection margin and the HPV test in predicting residual disease in subsequent hysterectomy sample s were estimated using the McNemar exact test . RESULTS : Univariable analysis showed that age , parity , menopausal status , gl and ular extension , and severity of disease were not predictive for residual disease , but positive resection margin and positive HPV tests were significant factors for predicting residual disease . These factors were also significant in a multivariable analysis ( positive resection margin 45.5 % , odds ratio [ OR ] 3.09 , 95 % confidence interval [ CI ] 1.19–8.03 , P=.021 ; positive HPV test 57.6 % , OR 11.05 , 95 % CI 4.01–30.49 , P<.001 ) . With resection margin , the sensitivity , specificity , and accuracy in predicting residual disease were 75 % , 53 % , and 61 % , respectively , whereas , with the HPV test , these values were 85 % , 67 % , and 73 % , respectively ( P=.454 , .080 , and .044 , respectively ) . Of patients with positive resection margins , 79 % of HPV-negative patients had no residual disease . Of patients with negative resection margins , no HPV-negative patient had residual disease . CONCLUSION : The HPV test after conization was significantly more accurate than resection margin for predicting residual disease . The predictive value of resection margin for predicting residual disease was much improved when used in combination with the HPV test . Use of the HPV test is recommended for identifying patients for subsequent hysterectomy after conization for CIN 3 and IA1 cancer . LEVEL OF EVIDENCE : AIM To investigate the therapeutic efficacy of cylindrical or cone-shaped excision performed by laser CO2 in the conservative management of persistent-recurrent high- grade cervical intraepithelial neoplasia ( HG-CIN ) in women of fertile age . PATIENTS AND METHODS Ninety-four premenopausal patients with persistent-recurrent HG-CIN had undergone re-conization or cylindrical excision according to the time of reappearance of the disease . The length of the procedures , intra- and postoperative complications , height of the excised specimens , final histological findings and follow-up data were retrospectively evaluated . RESULTS Fifty-five ( 58.5 % ) persistent and 39 ( 41.5 % ) recurrent cases had undergone cylindrical excision and st and ard re-conization respectively . All the treatments were successfully performed in an out-patient setting under local anesthesia with no differences in term of operative time , height of removed specimens , intra- and postoperative complications between the two groups . Definitive histology confirmed HG-CIN in 95.7 % of the cases and FIGO Stage Ia1 cervical cancer ( negative lymph vascular space involvement , LVSI ) in 4.3 % of the cases . The endocervical margins were involved in 3.6 % of the cylindrical ( persistent ) and in 17.9 % of the cone-shaped ( recurrent ) specimens ( p = 0.03 ) . The overall cure rate after a median follow-up time of 54 months ( range 10 - 196 ) was 91.5 % . A third excisional procedure was performed in 8 cases of persistent-recurrent HG-CIN with a disease-free subsequent follow-up of 38 months ( range 6 - 108 ) . CONCLUSION Cylindrical or conical re-excision performed by CO2 laser according to the time of reappearance of the disease seems to be a promising conservative approach for persistent-recurrent HG-CIN even though further r and omised prospect i ve studies are needed to confirm the long-term efficacy and reproductive outcomes OBJECTIVES Loop electrosurgical excision of the transformation zone ( LEETZ ) was recently associated with relatively high failure rates . We evaluated whether the combination of LEETZ with laser vaporization is superior to LEETZ alone in reducing the rates of recurrent abnormal cytology and residual disease . METHODS The study population included 426 women with histologic diagnosis of cervical intraepithelial neoplasia ( CIN ) 2 - 3 , of whom 289 ( study group ) were treated by LEETZ followed by laser vaporization of the crater base and walls and 137 ( control group ) were treated by LEETZ alone . All women were followed scrupulously at regular intervals for recurrent abnormal cytology and residual disease . The mean follow-up periods were 43 and 59 months for the study and control groups , respectively . RESULTS Both groups were derived from the same community and were similar in epidemiologic characteristics and disease severity . Although the incidence of positive surgical margins was similar in both groups ( 10.4 and 9.5 % for the study and control groups , respectively ) , recurrent abnormal cytology ( 10.2 % vs 5.5 % , P = 0.07 ) and histologic residual disease ( 21.4 % vs 0 % , P = 0.05 ) were more frequent among women in the control group . This applied to women with both negative and positive surgical margins . Both study and control women with positive surgical margins , especially at the endocervix , were at higher risk for recurrence . CONCLUSION The addition of laser vaporization to LEETZ may improve outcome of both women with positive margins and women with negative margins . Our results support conservative management for all treated women , regardless of cone margin status OBJECTIVE The goal of this study was to determine/evaluate the negative predictive value of human papillomavirus ( HPV ) testing following conization of cervix uteri . METHODS A prospect i ve analysis was undertaken on 79 cone biopsies of women with high- grade lesions ( cervical intraepithelial neoplasia ( CIN ) III ) . HPV testing was performed on cervical smears before and after conization . We correlated the margin status ( defined as positive cone margin or endocervical curettage status ) and positive conization HPV status with the residual disease in a hysterectomy specimen . A Digene II kit was used to perform HPV testing . HPV detection was done by Hybrid Capture assay . RESULTS Of the 79 patients , 47(59.5 % ) had positive margins after conization . HPV testing was positive in 37 cases ( 78.7 % ) and negative in 10 cases ( 21.3 % ) . Residual disease was found in 31 of 47 ( 66 % ) postconization hysterectomy specimens . No residual lesions were found in HPV-negative cases . Of the 32 cases with negative margins following conization , HPV testing was negative in 25 cases ( 78 % ) and was positive in 7 cases ( 22 % ) . Among these 25 cases with negative HPV tests , no residual lesion was detected , and in 7 HPV-positive cases , only one residual lesion was found . CONCLUSION HPV testing is potentially an effective tool in predicting residual dysplasia after conization and could potentially assist in the decision between hysterectomy and conservative follow-up in women with CIN III Objective To evaluate whether microcolposcopic topographic endocervical assessment reduces the failures of excisional treatment of cervical intraepithelial neoplasia ( C Output:	INTERPRETATION The risk of residual or recurrent CIN2 + is significantly greater with involved margins on excisional treatment ; however , high-risk HPV post-treatment predicts treatment failure more accurately than margin status .
MS21895	*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 Primary care physicians are well placed to identify patients in need of advance care planning ( ACP ) and initiate ACP in advance of an acute situation . OBJECTIVES This study aim ed to underst and Australian general practitioner ( GP ) clinical decision making relating to a patient 's " need for ACP " and the likelihood of initiating ACP . METHODS An experimental vignette study pseudor and omly manipulated factors thought to influence decision making regarding ACP . Patient-level factors included gender , age , type of disease , medical severity , openness to ACP , doctor-patient relationship , and family support . An accompanying demographic survey assessed health professional-level factors , including gender , years of experience , place of training , place of practice , caseload of patients with ACP , direct personal experience in ACP , and self-reported attitudes toward ACP . Seventy GPs were recruited , and each completed six unique vignettes , providing ratings of patient need for ACP , importance of initiating ACP in the coming months , and likelihood of initiating ACP at the next consultation . RESULTS Older patients , with malignant or cardiovascular disease , severe clinical presentations , good doctor-patient relationship , female gender , and poor family support were more likely to receive prompt ACP . Positive GP attitudes toward ACP were associated with greater likelihood of initiating ACP promptly . CONCLUSION Patients with presentations suggesting higher mortality risk were identified as being in need of ACP ; however , the likelihood of initiating ACP was sensitive to GP attitudes and psychosocial aspects of the doctor-patient interaction . Training material s aim ed at encouraging GP involvement in ACP should target attitudes toward ACP and communication skills , rather than focusing solely on prognostic risk This summary reflects on this monograph regarding multilevel intervention ( MLI ) research to 1 ) assess its added value ; 2 ) discuss what has been learned to date about its challenges in cancer care delivery ; and 3 ) identify specific ways to improve its scientific soundness , feasibility , policy relevance , and research agenda . The 12 su bmi tted chapters , and discussion of them at the March 2011 multilevel meeting , were review ed and discussed among the authors to elicit key findings and results addressing the questions raised at the outset of this effort . MLI research is underrepresented as an explicit focus in the cancer literature but may improve implementation of studies of cancer care delivery if they assess context ual , organizational , and environmental factors important to underst and ing behavioral and /or system-level interventions . The field lacks a single unifying theory , although several psychological or biological theories are useful , and an ecological model helps conceptualize and communicate interventions . MLI research design s are often complex , involving nonlinear and nonhierarchical relationships that may not be optimally studied in r and omized design s. Simulation modeling and pilot studies may be necessary to evaluate MLI interventions . Measurement and evaluation of team and organizational interventions are especially needed in cancer care , as are attention to the context of health-care reform , eHealth technology , and genomics-based medicine . Future progress in MLI research requires greater attention to developing and supporting relevant metrics of level effects and interactions and evaluating MLI interventions . MLI research holds an unrealized promise for underst and ing how to improve cancer care delivery Advance directives name a surrogate decision maker or provide written instructions with the intent of extending patient autonomy with respect to end-of-life decisions [ 1 - 3 ] . Supported on various grounds by the public [ 1 ] , physicians [ 4 ] , ethicists [ 5 ] , and legislators [ 6 ] , advance directives have also been promoted as a way to control the high costs of health care at the end of life [ 7 , 8 ] . Most patients are interested in establishing advance directives , but few actually complete them [ 1 , 9 , 10 ] . In 1990 , the U.S. Congress passed the Patient Self-Determination Act , which requires hospitals to inform admitted patients about their right to record advance directives [ 6 , 11 ] . The Act does not dictate who should initiate these discussion s ( patients , physicians , or an admissions officer , for example ) [ 12 , 13 ] . It is therefore not surprising that the Act has had little effect on the rate of completion of advance directives [ 11 , 13 - 15 ] . Because hospitalized patients are often acutely ill and lose their ability to make decisions [ 3 ] , it may be more appropriate to discuss such issues before hospitalization [ 12 , 16 , 17 ] . Other interventions aim ed at increasing the establishment of advance directives have met with mixed success [ 18 ] . With one exception [ 19 ] , patient education has had little or no effect [ 20 - 24 ] . More effective interventions have trained physicians , social workers , or counselors to discuss advance directives [ 18 , 22 , 25 - 27 ] ; this has led to the conclusion that counseling by a clinician is the best catalyst for the completion of advance directives [ 28 ] . However , little is known about how to educate and motivate clinicians to solicit advance directives [ 28 ] . We [ 29 - 31 ] and others [ 32 ] have previously shown that computer reminders increase physician compliance with practice guidelines . In this study , we tested the hypothesis that reminding primary care physicians to discuss advance directives would stimulate such discussion s and lead to the establishment of more advance directives . Methods Setting and Patients This study was approved by the institutional review board of Indiana University as expedited research with waiver of informed consent from both patients and physicians . It was conducted in the General Medicine Practice [ 31 ] , an academic primary care practice affiliated with an urban public teaching hospital . This practice is staffed by general internal medicine faculty , fellows , and residents . Each resident and fellow attends the General Medicine Practice one half-day per week ; faculty attend one to four half-days per week . Residents always practice with the same attending faculty physicians . All physicians , except for study investigators , were eligible to participate . At the time of this study , the General Medicine Practice comprised four separate practice s with separate waiting areas , clerks , and nurses . Each practice held eight half-day sessions per week . Each session was attended by two faculty members and two or three residents , each of whom provided primary care to assigned panels of patients . Residents were required to briefly discuss each patient with the attending faculty . Fellows served as faculty and were treated as such . Since 1981 , a computerized program has r and omly assigned new physicians to the practice sessions [ 31 ] . New patients have been sequentially assigned to open appointment slots ; this result ed in no important differences in patients or clinical practice among the sessions [ 29 , 33 ] . We included patients who were at risk for acute deterioration ( and therefore might benefit from advance directives ) because of advanced age ( 75 years , the typical threshold for the oldest old ) or because they were 50 years of age or older and had one of the following chronic conditions : cardiac ischemia , heart failure , chronic lung disease , cancer other than nonmelanomatous skin cancer , cerebrovascular disease , renal insufficiency , or cirrhosis . We chose 50 years of age as a cut-off to yield sufficient numbers of patients . A computer program identified eligible patients among those with scheduled appointments at the General Medicine Practice by using problem lists and test results stored in the Regenstrief Medical Record System [ 34 ] . Eligible patients who kept appointments at the General Medicine Practice were approached by research assistants in the waiting room . The research assistants , who were blinded at all times to the patients ' study groups , explained the study to the patients , invited them to participate , and interviewed those who agreed to participate ; patients from nursing homes and prisons and patients who were deaf or did not speak English were excluded . The assistants then administered the Pfeiffer Mental Status Question naire [ 35 ] ; patients whose scores indicated cognitive dysfunction were excluded . The remaining patients provided sociodemographic information and stated whether they had previously discussed or completed advance directives ; patients who had completed advance directives were excluded . Patients also stated their preferences with regard to six treatments in the event of a terminal illness [ 36 ] . Advance Directives Before the study , we created two separate forms for instruction directives and proxy directives ; these forms became the official advance directive documents of the hospital and its outpatient services . The instruction directive allowed patients to indicate whether , in the event of terminal illness and mental incapacity , they wanted or did not want eight types of care : cardiopulmonary resuscitation , mechanical ventilation , surgery , invasive procedures , nutrition and hydration , transfusion of blood or blood products , antibiotics , or noninvasive diagnostic tests . The primary care physician had to sign each completed instruction directive form to indicate that he or she was aware of its contents . The proxy directive design ated both primary and secondary health care representatives . We placed both advance directive forms in a drawer of the desk of each physician in the General Medicine Practice . We also placed the forms in a bin near the door of the staff room along with other forms and requisitions and business reply envelopes for patients who wanted to complete the forms at home . Research assistants entered the data from completed forms into the Regenstrief Medical Record System , where the forms were available for viewing through computer terminals and workstations in all inpatient and outpatient venues [ 34 ] . Before the study , the three physician-investigators presented the basic concepts of advance directives at gr and rounds . They also had face-to-face meetings with each physician in the General Medicine Practice and explained how to complete and process the forms . We encouraged physicians to discuss advance directives with their elderly and debilitated patients and posted flyers in each practice staffing room suggesting that physicians discuss advance directives with patients who had the target study conditions . Study Methods The intent of the r and omization scheme was to expose physicians to the same type of reminder or reminders , or no reminders , during all of their scheduled primary care visits with enrolled patients . At the time of this study , 32 weekly half-day sessions took place on the four General Medicine Practice practice s. Two sessions attended by study investigators were excluded . We r and omly assigned all of the physicians who worked in a particular half-day session to the same reminder category . At the time of r and omization , 16 physicians ( all of whom were faculty members ) practice d in more than 1 session per week ( 14 practice d in 2 sessions and 2 practice d in 3 sessions ) . Therefore , we r and omly assigned the sessions in a stepped manner by first allocating the 16 physicians and all of their associated sessions to four categories : control ( no reminders ) , computer-generated reminders for instruction directives , computer-generated reminders for proxy directives , and computer-generated reminders for both types of directives . We then r and omly assigned the remaining 8 sessions and their physicians to the four categories ( Table 1 ) . Each practice contained sessions in all four categories , which were equally distributed between mornings and afternoons . Table 1 . Results of R and omization All physicians routinely received computer-generated reminders for patients with scheduled visits . They were reminded to give preventive care , note abnormal test results , and avoid drug interactions [ 29 , 34 ] . These reminders appeared at the bottom of computer-generated printed encounter forms [ 34 ] ( Figure 1 ) . Physicians routinely review ed the encounter forms and the practice chart immediately before visiting the patient . As recommended by Litzelman and coworkers [ 37 ] , the advance directive reminders were followed by a choice list ( discussed today , next visit , not applicable , patient too ill , patient refuses to discuss , I disagree with advance directives ) . Instruction directives were called advance directives , and proxies were called health care representatives ( Figure 1 ) . Figure 1 . General Medicine Practice encounter form showing reminders for both types of advance directive . After patients were enrolled , research assistants attempted to interview them in the waiting room after each scheduled appointment to assess whether they had discussed advance directives with their physicians that day . Patients who answered yes were defined as having had an advance directive discussion . During the first scheduled General Medicine Practice visit in the 5-month period between 11 and 16 months after enrollment , a close-out interview was attempted . If no scheduled visit had occurred by 15 months after enrollment , the close-out interview was attempted by telephone . Form completion was defined as having occurred if either completed form was received between study enrollment and 30 days after the final interview ( this made it possible to receive by mail forms that were completed after the close-out OBJECTIVE : To determine efficient ways of promoting advance directives among heterogeneous population s of elderly ambulatory patients . DESIGN : One-year quasi-experimental trial . SETTING : Five suburban and urban health centers in one region of a large managed care organization . One additional suburban center served as a control site . PARTICIPANTS : Individuals ages 65 and older ( N=2,120 ) who were continuously enrolled and had a health maintenance visit with their primary care provider during the study year . INTERVENTION : Physician education ( oral and written ) and physician and patient prompts to discuss advance directives . MAIN RESULTS : Sixty-six ( 7.8 % ) of patients at the intervention centers completed new advance directives , versus 9 of 1,277 ( < 1 % ) at the comparison center ( P<.001 ) . Patients 75 and older were twice as likely ( odds ratio [ OR ] , 2.0 ; 95 % confidence limits [ CL ] , 1.2 to 3.3 ) as those 65 to 74 to file a new advance directive , and the odds were twice as great ( OR , 2.6 ; 95 % CL , 1.4 to 4.6 ) at centers serving communities with median household income over the state median . Gender , recent hospitalization , emergency room visits , and number of chronic conditions were not related to making new directives nor was predominant ethnicity of the center community ( African-American versus white ) . Adjusted for these factors , the intervention result ed in a 20-fold increase ( 95 % CL , 10.4 to 47.8 ) in the odds of creating a new advance directive . Doctors reported barriers of time and unwillingness to press discussion s with patients . CONCLUSIONS : A replicable intervention largely targeting doctors Output:	Review findings identified a diverse and disaggregated body of ACP literature describing barriers and enablers to ACP in general practice , and interventions testing single or multiple mechanisms to improve ACP generally without explicit consideration for level of influence .
MS21896	*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 Screening with serum prostate specific antigen testing leads to the detection of many prostate cancers early in their natural history . Statistical models have been proposed to predict indolent cancer . We vali date d and up date d model predictions for a screening setting . MATERIAL S AND METHODS We selected 247 patients with clinical stage T1C or T2A from the European R and omized Study on Screening for Prostate Cancer who were treated with radical prostatectomy . We vali date d a nomogram that had previously been developed in a clinical setting . Predictive characteristics were serum prostate specific antigen , ultrasound prostate volume , clinical stage , prostate biopsy Gleason grade , and total length of cancer and noncancer tissue in biopsy cores . Indolent cancer was defined as pathologically organ confined cancer 0.5 cc or less in volume without poorly differentiated elements . Logistic regression was used to up date the previous model and examine the contribution of other potential predictors . RESULTS Overall 121 of 247 patients ( 49 % ) had indolent cancer , while the average predicted probability was around 20 % ( p < 0.001 ) . Effects of individual variables were similar to those found before and discriminative ability was adequate ( AUC 0.76 ) . An up date d model was constructed , which merely recalibrated the nomogram and did not apply additional predictors . CONCLUSIONS Prostate cancers identified in a screening setting have a substantially higher likelihood of being indolent than those predicted by a previously proposed nomogram . However , an up date d model can support patients and clinicians when the various treatment options for prostate cancer are considered BACKGROUND There is no conclusive evidence that screening based on serum prostate-specific antigen ( PSA ) tests decreases prostate-cancer mortality . Since its introduction in the USA around 1990 , uptake of PSA testing has been rapid in the USA , but much less common in the UK . Our aim was to study trends over time in prostate-cancer mortality and incidence in the USA and UK in 1975 - 2004 , and compare these patterns with trends in screening and treatment . METHODS Joinpoint regression analysis of cancer-mortality statistics from Cancer Research UK ( London , UK ) and from the US National Cancer Institute Surveillance , Epidemiology and End Results ( SEER ) programme from 1975 to 2004 was used to estimate the annual percentage change in prostate-cancer mortality in both countries and the points in time when trends changed . The ratio of USA to UK age-adjusted prostate-cancer incidence was also assessed . FINDINGS Age-specific and age-adjusted prostate-cancer mortality peaked in the early 1990s at almost identical rates in both countries , but age-adjusted mortality in the USA subsequently declined after 1994 by -4.17 % ( 95 % CI -4.34 to -3.99 ) each year , four-times the rate of decline in the UK after 1992 ( -1.14 % [ -1.44 to -0.84 ] ) . The mortality decline in the USA was greatest and most sustained in patients aged 75 years or older ( -5.32 % [ -8.23 to -2.32 ] ) , whereas death rates had plateaued in this age group in the UK by 2000 . The mean ratio of USA to UK age-adjusted prostate-cancer incidence rates in 1975 - 2003 was 2.5 , with a pronounced peak around the time that PSA testing was introduced in the USA . Numbers needed to treat to prevent one death from prostate cancer were 33 000 in the 55 - 64-year age group . INTERPRETATION The striking decline in prostate-cancer mortality in the USA compared with the UK in 1994 - 2004 coincided with much higher uptake of PSA screening in the USA . Explanations for the different trends in mortality include the possibility of an early effect of initial screening rounds on men with more aggressive asymptomatic disease in the USA , different approaches to treatment in the two countries , and bias related to the misattribution of cause of death . Speculation over the role of screening will continue until evidence from r and omised controlled trials is published A consensus meeting on screening and global strategy for prostate carcinoma , held in Antwerp in 1994 , determined the willingness among European cancer prevention centers to pursue vigorously the collaborative formation of a multinational r and omized screening trial . This trial was to be named the European R and omized Study of Screening for Prostate Cancer ( ERSPC ) PURPOSE Despite the tremendous stage migration associated with prostate cancer screening to our knowledge it remains unproven whether prostate specific antigen based screening decreases prostate cancer specific mortality . Recent studies have shown that prostate specific antigen velocity more than 2 ng/ml per year in the year before diagnosis is associated with a significantly greater risk of prostate cancer specific mortality after treatment . This may serve as a surrogate marker for prostate cancer outcomes . We compared the prostate specific antigen velocity profile between patients with prostate cancer in whom the tumor was detected in a formal screening study and those who were referred for treatment . MATERIAL S AND METHODS We evaluated prostate specific antigen velocity in 1,101 men from a prostate cancer screening study and in 368 not enrolled in a screening study who were referred for treatment . All patients underwent radical prostatectomy for clinical ly localized disease and had multiple preoperative prostate specific antigen measurements to calculate prostate specific antigen velocity . RESULTS Median prostate specific antigen velocity before diagnosis was significantly higher in referred vs screened men ( 1.35 vs 0.68 ng/ml per year , p < 0.0001 ) . In addition , a significantly greater proportion of referred patients had prostate specific antigen velocity more than 2 ng/ml per year ( 38 % vs 17 % , p < 0.0001 ) . On multivariate analysis using prostate specific antigen , clinical stage and biopsy Gleason score screened vs referred status was a significant independent predictor of prostate specific antigen velocity more than 2 ng/ml per year ( p < 0.0004 ) . CONCLUSIONS Prostate specific antigen velocity more than 2 ng/ml per year has been linked to a significantly greater risk of prostate cancer specific mortality . Patients who underwent serial screening had a more favorable prostate specific antigen velocity profile at diagnosis , suggesting that screen detected prostate cancer may be more likely to be cured with definitive therapy OBJECTIVES To determine the prostate-specific antigen ( PSA ) velocity , PSA slope , and PSA doubling time ( PSADT ) in men with positive biopsies , negative biopsies , and no biopsy indications 4 years after an initial screening ; and to use this information to improve the test characteristics in the early detection of prostate cancer and provide normal values for these parameters in screened men with and without evidence of prostate cancer . METHODS Within the European R and omized Study of Screening for Prostate Cancer , section Rotterdam , we identified 9575 men with a second determination of PSA 4 years after the initial screening . These men were divided into three groups : men with positive biopsies , negative biopsies , and no biopsy indications in the second round ( PSA less than 3.0 ng/mL ) . The predictive values of PSA dynamics for detection of prostate cancer were calculated . RESULTS The mean PSA velocity of men with prostate cancer was 0.62 ng/mL/yr versus 0.46 ng/mL/yr for men with a negative biopsy ( P = 0.001 ) . The mean PSADT for men with prostate cancer was 5.1 years and for those with a negative biopsy it was 6.1 years ( P = 0.002 ) . The PSADT for men with no indication for biopsy was 25.1 years . However , receiver operating characteristic analyses revealed only a moderate value for these test parameters in predicting biopsy outcome . CONCLUSIONS The mean values of PSA velocity , PSA slope , and PSADT in a rescreened population differed significantly between men with and without prostate cancer . However , in predicting the biopsy outcome , the PSA dynamics were of limited value In a study of 2,400 r and omly selected men ( age 55 - 70 years ) for early detection of prostate cancer the authors have compared the diagnostic value of digital rectal examination ( DRE ) , transrectal ultrasound ( TRUS ) and prostate specific antigen ( PSA ) . Altogether 62 prostate cancers were detected , corresponding to a detection rate of 3.5 % but by use of DRE the detection rate was only 2.3 % . The study showed that TRUS added significantly to the detection rate . If radical surgery is restricted to stages T1 and T2A , the combined use of DRE and TRUS detected twice as many cases fit for this treatment than DRE alone . The authors advocate r and omized studies for evaluation of early radical treatment of prostate cancer . Before results of such studies have appeared they recommend method ological studies aim ed at development and enhancement of the accuracy of the diagnostic tools PURPOSE Early detection of prostate cancer has been recommended for men with affected first-degree relatives despite the lack of evidence for mortality reduction . We therefore evaluated the impact of family history in the Finnish prostate cancer screening trial . PATIENTS AND METHODS Approximately 80,000 men were identified from the population register for the first screening round . Of the 32,000 men r and omized to the screening arm , 30,403 were eligible at the time of invitation . A blood sample was drawn from the participants ( n = 20,716 ) , and serum prostate-specific antigen ( PSA ) was determined . Men with a PSA level > or = 4.0 ng/mL were referred for prostate biopsy . Information on family history was obtained through a self-administered question naire at baseline . RESULTS A total of 964 ( 5 % ) of the 20,716 screening participants had a positive family history , and 105 ( 11 % ) were screening-positive . Twenty-nine tumors were diagnosed , corresponding to a detection rate of 3.0 % ( 29 of 964 ) and a positive predictive value of 28 % ( 29 of 105 ) . Of the 19,347 men without a family history , 1,487 ( 8 % ) had a PSA level > or = 4.0 ng/mL. The detection rate was 2.4 % ( 462 of 19,347 ) and the positive predictive value was 31 % ( 462 of 1,487 ) . The risk associated with a positive family history was not substantially increased ( rate ratio , 1.3 ; 95 % confidence interval , 0.9 to 1.8 ) . The results were not affected by the age of the screenee or age at diagnosis of the affected relative . The program sensitivity was 6 % ( 29 of 491 ) ( ie , selective screening policy would have missed 94 % of cancers in the population ) . No differences were seen in the characteristics of screen-detected cancers by family history . CONCLUSION Our findings provide no support for selective screening among men with affected relatives The Prostate , Lung , Colorectal and Ovarian ( PLCO ) Cancer Screening Trial is enrolling 148,000 men and women ages 55 - 74 at ten screening centers nationwide with balanced r and omization to intervention and control arms . For prostate cancer , men receive a digital rectal examination and a blood test for prostate-specific antigen . For lung cancer , men and women receive a posteroanterior view chest X-ray . For colorectal cancer , men and women undergo a 60-cm flexible sigmoidoscopy . For ovarian cancer , women receive a blood test for the CA125 tumor marker and transvaginal ultrasound . Members of the control arm continue with their usual care . Follow-up in both groups will continue for at least 13 years from r and omization to assess health status and cause of death . The primary endpoint is mortality from the four PLCO cancers , which accounts for about 53 % of all cancer deaths in men and 41 % of cancer deaths in women in the United States each year . Blood specimens are collected from screened participants , buccal cell DNA from controls , and histology slides from cases ; these are maintained in a biorepository . Participants complete a baseline question naire ( covering health status and risk factors ) and a dietary question naire . More than 12,000 participants were enrolled in the pilot phase ( concluded in September 1994 ) . Changes in the eligibility criteria followed . As of April 2000 , enrollment exceeded 144,500 . Data are scanned into design ated on-site computers for uploading by participant identification number to the coordinating center for quality checks , archival storage , and preparation of analysis data sets for use by the National Cancer Institute ( NCI ) . Scientific direction is provided by NCI scientists , trial investigators , external consultants , and an independent data safety and monitoring board . Performance and data quality are monitored via data edits , site visits , r and om record audits , and teleconferences . The PLCO trial is formally endorsed by the American Cancer Society and has been ranked by the American Urological Association as one of the most important prostate cancer studies being conducted . Special efforts to enroll black participants are cosponsored by the U.S. Centers for Disease Control and Prevention BACKGROUND Residents are required to demonstrate competency in communication skills . Prostate cancer screening discussion s are examples of complex physician-patient communication processes , requiring an objective presentation of the known risks , potential benefits , and scientific uncertainties surrounding screening . National organizations recommend shared decision making ( SDM ) in these discussion s. METHODS A stratified analysis to contrast resident and faculty outcomes was planned as part of a r and omized controlled trial comparing decision aids for prostate cancer screening in a suburban Washington , DC , residency practice . All Output:	AUTHORS ' CONCLUSIONS Given that only two r and omised controlled trials were included , and the high risk of bias of both trials , there is insufficient evidence to either support or refute the routine use of mass , selective or opportunistic screening compared to no screening for reducing prostate cancer mortality .
MS21897	*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 Heart and coronary calcifications in hemodialysis patients are of very common occurrence and linked to cardiovascular events and mortality . Several studies have been published with similar results . Most of them were mainly cross-sectional and some of the prospect i ve protocol s were aim ed to evaluate the results of the control of altered biochemical parameters of mineral disturbances with special regard to serum calcium , phosphate and CaxP with the use of calcium containing and calcium free phosphate chelating agents . The aim of the present study was to evaluate in hemodialysis patients classic and some non classic risk factors as predictors of calcification changes after one year and to evaluate the impact of progression on survival . Methods 81 patients on hemodialysis were studied , with a wide age range and HD vintage . Several classic parameters and some less classic risk factors were studied like fetuin-A , CRP , 25-OHD and leptin . Calcifications , as Agatston scores , were evaluated with Multislice CT basally and after 12 - 18 months . Results Coronary artery calcifications were observed in 71 of 81 patients . Non parametric correlations between Agatston scores and Age , HD Age , PTH and CRP were significant . Delta increments of Agatston scores correlated also with serum calcium , CaxP , Fetuin-A , triglycerides and serum albumin . Logistic regression analysis showed Age , PTH and serum calcium as important predictors of Delta Agatston scores . LN transformation of the not normally distributed variables restricted the significant correlations to Age , BMI and CRP . Considering the Delta Agatston scores as dependent , significant predictors were Age , PTH and HDL . A strong association was found between basal calcification scores and Delta increment at one year . By logistic analysis , the one year increments in Agatston scores were found to be predictors of mortality . Diabetic and hypertensive patients have significantly higher Delta scores . Conclusions Progression of calcification is of common occurrence , with special regard to elevated basal scores , and is predictive of survival . Higher predictive value of survival is linked to the one year increment of calcification scores . Some classic and non classic risk factors play an important role in progression . Some of them could be controlled with appropriate management with possible improvement of mortality BACKGROUND AND OBJECTIVES Hyperphosphatemia , vitamin D deficiency , hyperparathyroidism , and high serum fibroblast growth factor 23 ( FGF23 ) levels , when studied separately , were found to predict the progression of CKD . However , studies with simultaneous measurement of mineral bone disorder (MBD)-related factors were scarce . This study aim ed to identify factors predicting renal outcome independent of other factors . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS This was a prospect i ve cohort study of 738 Japanese predialysis out patients in the nephrology departments of two hospitals . The outcome was defined as a doubling of serum creatinine or initiation of dialysis . RESULTS Mean estimated GFR ( eGFR ) was 35 ml/min per 1.73 m(2 ) . At enrollment , the increase in intact FGF23 with decreasing eGFR was the earliest among changes in MBD-related factors , followed by 1,25-dihydroxyvitamin D decrease , parathyroid hormone increase , and phosphate increase . During a median duration of 4.4 years , 213 patients reached the endpoint . In a multivariable Cox model , high FGF23 and low 25-hydroxyvitamin D ( 25D ) levels were the only MBD-related factors associated with a higher risk of renal endpoint ( adjusted hazard ratio [ 95 % confidence interval ] per unit change of log FGF23 and 10 ng/ml of 25D : 1.83 [ 1.28 - 2.61 ] and 0.61 [ 0.41 - 0.90 ] , respectively ) . There was no significant interaction between 25D and FGF23 ( P=0.11 ) . Active vitamin D therapy , serum phosphate , 1,25-dihydroxyvitamin D , and parathyroid hormone levels were not related to the renal endpoint . Treating death as a competing risk or multiple imputation for missing values yielded similar results . CONCLUSIONS Combined use of two markers is useful for the risk stratification of renal outcome Background — Patients with kidney disease have disordered bone and mineral metabolism , including elevated serum concentrations of fibroblast growth factor-23 ( FGF23 ) . These elevated concentrations are associated with cardiovascular and all-cause mortality . The objective was to determine the effects of the calcimimetic cinacalcet ( versus placebo ) on reducing serum FGF23 and whether changes in FGF23 are associated with death and cardiovascular events . Methods and Results — This was a secondary analysis of a r and omized clinical trial comparing cinacalcet to placebo in addition to conventional therapy ( phosphate binders/vitamin D ) in patients receiving hemodialysis with secondary hyperparathyroidism ( intact parathyroid hormone ≥300 pg/mL ) . The primary study end point was time to death or a first nonfatal cardiovascular event ( myocardial infa rct ion , hospitalization for angina , heart failure , or a peripheral vascular event ) . This analysis included 2985 patients ( 77 % of r and omized ) with serum sample s at baseline and 2602 patients ( 67 % ) with sample s at both baseline and week 20 . The results demonstrated that a significantly larger proportion of patients r and omized to cinacalcet had ≥30 % ( 68 % versus 28 % ) reductions in FGF23 . Among patients r and omized to cinacalcet , a ≥30 % reduction in FGF23 between baseline and week 20 was associated with a nominally significant reduction in the primary composite end point ( relative hazard , 0.82 ; 95 % confidence interval , 0.69–0.98 ) , cardiovascular mortality ( relative hazard , 0.66 ; 95 % confidence interval , 0.50–0.87 ) , sudden cardiac death ( relative hazard , 0.57 ; 95 % confidence interval , 0.37–0.86 ) , and heart failure ( relative hazard , 0.69 ; 95 % confidence interval , 0.48–0.99 ) . Conclusions — Treatment with cinacalcet significantly lowers serum FGF23 . Treatment-induced reductions in serum FGF23 are associated with lower rates of cardiovascular death and major cardiovascular events . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00345839 BACKGROUND In chronic kidney disease stage 5D , diagnostic usefulness of bone mineral density ( BMD ) in predicting fracture has not been established because of variable results in previous studies . The reason for this may be the heterogeneity of underlying pathogenesis of the fracture . METHODS BMD was measured annually and serum biochemistry monthly for 485 hemodialyzed patients from April 2003 to March 2008 , and all fractures were recorded . RESULTS Forty-six new episodes of any type of fracture and 29 cases of prevalent spine fracture were recorded . Serum bone-specific alkaline phosphatase ( b-AP ) was a very useful surrogate marker for any type of incident fracture risk [ area under curve ( AUC ) = 0.766 , P < 0.0001 ] . A significantly greater risk of any type of incident fracture was associated with parathyroid hormone ( PTH ) levels either < 150 pg/mL [ hazard ratio ( HR ) = 3.47 , P < 0.01 ] or > 300 pg/mL ( HR = 5.88 , P < 0.0001 ) compared with 150 - 300 pg/mL. Receiver-operating characteristic analysis demonstrated a significant predictive power for incident of any type of fracture by BMD at the total hip ( AUC = 0.760 , P < 0.0001 ) and other hip regions in females in the lower PTH group ( PTH < 204 pg/mL ) . BMDs at every site but whole body or lumbar spine had significant power to discriminate prevalent spine fracture regardless of gender or PTH . CONCLUSIONS Hemodialyzed patients with low or high PTH or increased b-AP had a high fracture risk . BMD by Dual Energy X-ray Absorptiometry ( DEXA ) , especially at the total hip region , was useful to predict any type of incident of fracture for females with low PTH or to discriminate prevalent spine fracture for every patient BACKGROUND AND OBJECTIVES Higher phosphate is associated with mortality in dialysis patients but few prospect i ve studies assess this in nondialysis patients managed in an outpatient nephrology clinic . This prospect i ve longitudinal study examined whether phosphate level was associated with death in a referred population . DESIGN , SETTING , PARTICIPANTS & MEASUREMENTS Patients ( 1203 ) of nondialysis chronic kidney disease ( CKD ) in the Chronic Renal Insufficiency St and ards Implementation Study were assessed . Survival analyses were performed for quartiles of baseline phosphate relative to GFR , 12-month time-averaged phosphate , and baseline phosphate according to published phosphate targets . RESULTS Mean ( SD ) eGFR was 32 ( 15 ) ml/min per 1.73 m(2 ) , age 64 ( 14 ) years , and phosphate 1.2 ( 0.30 ) mmol/L. Cox multivariate adjusted regression in CKD stages 3 to 4 patients showed an increased risk of all-cause and cardiovascular mortality in the highest quartile compared with that in the lowest quartile of phosphate . No association was found in CKD stage 5 patients . Patients who had values above recommended targets for phosphate control had increased risk of all-cause and cardiovascular death compared with patients below target . The highest quartile compared with the lowest quartile of 12-month time-averaged phosphate was associated with an increased risk of mortality . CONCLUSIONS In CKD stages 3 to 4 patients , higher phosphate was associated with a stepwise increase in mortality . As phosphate levels below published targets ( as opposed to within them ) are associated with better survival , guidelines for phosphate in nondialysis CKD patients should be re-examined . Intervention trials are required to determine whether lowering phosphate will improve survival Background Serum phosphate is a known risk factor for cardiovascular events and mortality in people with chronic kidney disease ( CKD ) , however data on the association of these outcomes with serum phosphate in the general population are scarce . We investigate this relationship in people with and without CKD in a large community-based population . Methods Three groups from an adult cohort of the Quality Improvement in Chronic Kidney Disease ( QICKD ) cluster r and omised trial ( IS RCT N56023731 ) were followed over a period of 2.5 years : people with normal renal function ( N = 24,184 ) , people with CKD stages 1–2 ( N = 20,356 ) , and people with CKD stages 3–5 ( N = 13,292 ) . We used a multilevel logistic regression model to determine the association between serum phosphate , in these groups , and a composite outcome of all-cause mortality , cardiovascular events , and advanced coronary artery disease . We adjusted for known cardiovascular risk factors . Findings Higher phosphate levels were found to correlate with increased cardiovascular risk . In people with normal renal function and CKD stages 1–2 , Phosphate levels between 1.25 and 1.50 mmol/l were associated with increased cardiovascular events ; odds ratio ( OR ) 1.36 ( 95 % CI 1.06–1.74 ; p = 0.016 ) in people with normal renal function and OR 1.40 ( 95 % CI 1.09–1.81 ; p = 0.010 ) in people with CKD stages 1–2 . Hypophosphatemia ( < 0.75 mmol/l ) was associated with fewer cardiovascular events in people with normal renal function ; OR 0.59 ( 95 % CI 0.36–0.97 ; p = 0.049 ) . In people with CKD stages 3–5 , hyperphosphatemia ( > 1.50 mmol/l ) was associated with increased cardiovascular risk ; OR 2.34 ( 95 % CI 1.64–3.32 ; p<0.001 ) . Other phosphate ranges were not found to have a significant impact on cardiovascular events in people with CKD stages 3–5 . Conclusions Serum phosphate is associated with cardiovascular events in people with and without CKD . Further research is required to determine the mechanisms underlying these associations BACKGROUND The management of chronic kidney disease-mineral and bone disorder requires the assessment of bone turnover , which most often is based on parathyroid hormone ( PTH ) concentration , the utility of which remains controversial . STUDY DESIGN Cross-sectional retrospective diagnostic test study . SETTING & PARTICIPANTS 492 dialysis patients from Brazil , Portugal , Turkey , and Venezuela with prior bone biopsy and stored ( -20 ° C ) serum . IN Output:	However , the studies did not show consistent beneficial effects of osteoporosis medications on BMD . In conclusion , DXA BMD assessment is reasonable if low or decreasing BMD will lead to additional interventions to reduce falls or recommendations for use of osteoporosis medications . The analysis underscored the importance of potential interactions among components of CKDMBD in terms of risk prediction for death or cardiovascular events . High- quality evidence now links high phosphate concentrations with mortality among patients with CKD stage G3a to G5 and transplant recipients ( 1928 ) . However , there is still a lack of data from clinical trials showing that therapeutic approaches to decreasing serum phosphate levels improve patient-centered outcomes . The 2009 guideline suggested maintenance of normal serum phosphate levels for patients with CKD stages G3a to G4 . Most studies found phosphate to be consistently associated with excess mortality at levels above and below the limits of normal but not in the normal range .
MS21898	*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: Genetic risk prediction has several potential applications in medical research and clinical practice and could be used , for example , to stratify a heterogeneous population of patients by their predicted genetic risk . However , for polygenic traits , such as psychiatric disorders , the accuracy of risk prediction is low . Here we use a multivariate linear mixed model and apply multi-trait genomic best linear unbiased prediction for genetic risk prediction . This method exploits correlations between disorders and simultaneously evaluates individual risk for each disorder . We show that the multivariate approach significantly increases the prediction accuracy for schizophrenia , bipolar disorder , and major depressive disorder in the discovery as well as in independent validation data sets . By grouping SNPs based on genome annotation and fitting multiple r and om effects , we show that the prediction accuracy could be further improved . The gain in prediction accuracy of the multivariate approach is equivalent to an increase in sample size of 34 % for schizophrenia , 68 % for bipolar disorder , and 76 % for major depressive disorders using single trait models . Because our approach can be readily applied to any number of GWAS data sets of correlated traits , it is a flexible and powerful tool to maximize prediction accuracy . With current sample size , risk predictors are not useful in a clinical setting but already are a valuable research tool , for example in experimental design s comparing cases with high and low polygenic risk BACKGROUND Cognitive impairment in schizophrenia-spectrum disorders is highly prevalent and notably influences functional outcomes . AIMS To characterise the cognitive effectiveness of second-generation antipsychotic drugs . METHOD One hundred consecutive and previously unmedicated patients with first-episode schizophrenia-spectrum disorders were admitted . Seventy-seven completed baseline , 1-month and 6-month psychopathological and neuropsychological assessment s. Patients were r and omised to risperidone or olanzapine treatment . Four final treatment allocation groups were defined since patients continued treatment in their normal setting : risperidone , olanzapine , mixed and no-antipsychotic groups . RESULTS There were no differences in cognitive effectiveness between the four treatment groups . Reliable change index methods demonstrated that nearly a half of patients showed an improvement in Global Cognitive Score at the 6-month assessment . Improvement on the neuropsychological tests ranged from 17 to 54 % . A strong predictor of cognitive response was poor performance on baseline neuropsychological tests ; response was moderately influenced by a low premorbid scholastic performance and IQ . CONCLUSIONS Cognitive improvement related to second-generation antipsychotic drugs appeared within the first 4 weeks of treatment and persisted at 6 months irrespective of treatment group . Greater cognitive dysfunction at baseline and lower premorbid cognitive background predicted cognitive improvement in our sample BACKGROUND The purpose of this investigation was to test the efficacy of novel antipsychotic medications in the treatment of cognitive impairment in early phase schizophrenia . METHODS Sixty-five patients in this multicenter double-blind study were r and omly assigned to olanzapine ( 5 - 20 mg ) , risperidone ( 4 - 10 mg ) , or haloperidol ( 5 - 20 mg ) . St and ard measures of clinical and motor syndromes were administered , as well as a comprehensive battery of tests to assess ( 1 ) motor skills , ( 2 ) attention span , ( 3 ) verbal fluency and reasoning , ( 4 ) nonverbal fluency and construction , ( 5 ) executive skills , and ( 6 ) immediate recall at baseline and after 6 , 30 , and 54 weeks of treatment . RESULTS The general cognitive index derived from the 6 domain scores revealed a significantly greater benefit from treatment with olanzapine relative to haloperidol and olanzapine relative to risperidone , but no significant difference was shown between risperidone and haloperidol . The improvement related to olanzapine was apparent after 6 weeks and enhanced after 30 and 54 weeks of treatment . Exploratory within-group analyses of the 6 cognitive domains after a conservative Bonferroni adjustment revealed a significant improvement with olanzapine only on the immediate recall domain , and similar analyses of the 17 individual tests revealed a significant improvement with olanzapine only on the Hooper Visual Organization Test . CONCLUSIONS These data suggest that olanzapine has some superior cognitive benefits relative to haloperidol and risperidone . A larger sample replication study is necessary to confirm and generalize the observations of this study and begin evaluation of the implication s of this change to cerebral function and quality of life for people with schizophrenia The study investigated the non-inferiority of flupentixol compared to risperidone in the treatment of negative symptoms . In addition , the effects of flupentixol on mood and cognitive symptoms were explored . In a r and omized , double-blind multicenter study , 144 non-acute schizophrenia patients with predominant negative symptoms were treated with a flexible dose of either flupentixol ( 4 - 12 mg/d ) or risperidone ( 2 - 6 mg/d ) for up to 25 weeks . In addition to a non-inferiority analysis , a principal component analysis ( PCA ) of the PANSS was performed post hoc . Regarding negative symptoms , flupentixol proved to be non-inferior to risperidone . Both drugs improved depressed mood with effect sizes favoring flupentixol . PCA suggested a five-factor structure . Effect sizes for the cognitive factor were up to 0.74 for flupentixol and up to 0.80 for risperidone . EPS scores were rather low and Parkinsonism improved in both groups , but anticholinergic drugs were prescribed significantly more frequently in the flupentixol group , which generally showed significantly more adverse events . Results indicate that the 1st generation antipsychotic flupentixol improves negative , affective and cognitive symptoms in chronic schizophrenia comparable to risperidone . Further studies should confirm the latter using neuropsychological performance tests and should investigate whether tolerability improves with a markedly lower dose range OBJECTIVE Newer antipsychotic drugs have shown promise in ameliorating neurocognitive deficits in patients with schizophrenia , but few studies have compared newer antipsychotic drugs with both clozapine and conventional agents , particularly in patients who have had suboptimal response to prior treatments . METHOD The authors examined the effects of clozapine , olanzapine , risperidone , and haloperidol on 16 measures of neurocognitive functioning in a double-blind , 14-week trial involving 101 patients . A global score was computed along with scores in four neurocognitive domains : memory , attention , motor function , and general executive and perceptual organization . RESULTS Global neurocognitive function improved with olanzapine and risperidone treatment , and these improvements were superior to those seen with haloperidol . Patients treated with olanzapine exhibited improvement in the general and attention domains but not more than that observed with other treatments . Patients treated with risperidone exhibited improvement in memory that was superior to that of both clozapine and haloperidol . Clozapine yielded improvement in motor function but not more than in other groups . Average effect sizes for change were in the small to medium range . More than half of the patients treated with olanzapine and risperidone experienced " clinical ly significant " improvement ( changes in score of at least one-half st and ard deviation relative to baseline ) . These findings did not appear to be mediated by changes in symptoms , side effects , or blood levels of medications . CONCLUSIONS Patients with a history of suboptimal response to conventional treatments may show cognitive benefits from newer antipsychotic drugs , and there may be differences between atypical antipsychotic drugs in their patterns of cognitive effects OBJECTIVE To investigate the neurocognitive effectiveness of haloperidol , risperidone , and olanzapine in first-episode schizophrenia-spectrum disorders . METHOD This prospect i ve , r and omized , open-label study was conducted from February 2001 to February 2005 . Data for the present investigation were obtained from a large epidemiologic and 3-year longitudinal intervention program of first-episode psychosis ( DSM-IV criteria ) conducted at the outpatient clinic and the inpatient unit at the University Hospital Marques de Valdecilla , Sant and er , Spain . One hundred four patients r and omly assigned to haloperidol ( N = 35 ) , olanzapine ( N = 30 ) , or risperidone ( N = 39 ) who completed clinical and cognitive evaluations at baseline , 6 months , and 1 year were included in the final analysis . Thirty-seven healthy individuals were also longitudinally assessed . A neuropsychological battery that comprised 9 cognitive domains was used . The contribution of clinical changes , concomitant medications , and the severity of motor side effects to cognitive changes was controlled . The main outcome measure was cognitive changes at 1-year follow-up . RESULTS The 3 treatment groups showed a significant improvement in cognitive scores after 1 year . The differential cognitive effectiveness between antipsychotics was insignificant . The magnitude of cognitive changes was similar in the 3 treatment groups and controls , although a greater improvement on the Finger Tapping Test , Trail Making Test B , and Rey Complex Figure Test was found in the treatment groups . Clinical changes , use of concomitant medications , and the emergence of motor side effects did not significantly account for cognitive changes over time . CONCLUSION Haloperidol , olanzapine , and risperidone were equally effective in treating cognitive deficits of psychosis . The effect of practice clearly contributes to cognitive score improvements after treatment with antipsychotics . Our results provide important information regarding the practical utility of antipsychotic treatments to improve cognition and could have implication s for developing novel approaches for cognitive pharmacotherapy in schizophrenia OBJECTIVE The authors sought to compare the effects of olanzapine , quetiapine , and risperidone on neurocognitive function in patients with early psychosis . METHOD In a 52-week double-blind , multicenter study , 400 patients early in the course of psychotic illness ( < 5 years ) were r and omly assigned to treatment with olanzapine ( 2.5 - 20 mg/day ) , quetiapine ( 100 - 800 mg/day ) , or risperidone ( 0.5 - 4 mg/day ) . The mean modal daily dose was 11.7 mg ( SD=5.3 ) for olanzapine , 506 mg ( SD=215 ) for quetiapine , and 2.4 mg ( SD=1.0 ) for risperidone . A total of 224 patients completed neurocognitive assessment s at baseline and at 12 weeks , and 81 patients also completed them at 52 weeks . Neurocognitive composite scores were calculated from the neurocognitive battery used in the Clinical Antipsychotic Trials of Intervention Effectiveness ( CATIE ) and from the Brief Assessment of Cognition in Schizophrenia . RESULTS At week 12 , there was significant improvement in neurocognition for each treatment ( p<0.01 ) , but no significant overall difference between treatments . Composite z score improvements on the CATIE neurocognitive battery were 0.17 for olanzapine , 0.33 for quetiapine , and 0.32 for risperidone . Composite z score improvements on the Brief Assessment of Cognition in Schizophrenia were 0.19 for olanzapine , 0.34 for quetiapine , and 0.22 for risperidone . Statistically significant relationships between improvements in neurocognition and functional outcome were observed at weeks 12 and 52 . CONCLUSIONS Olanzapine , quetiapine , and risperidone all produced significant improvements in neurocognition in early-psychosis patients . Although cognitive improvements were modest , their clinical importance was suggested by relationships with improvements in functional outcome OBJECTIVE To compare the consequences of a guided discontinuation strategy and maintenance treatment in remitted first-episode psychosis in terms of relapse rates and functional outcome . METHOD The study was conducted in 7 mental health care organizations and the Department of Psychiatry of the University Medical Center Groningen in The Netherl and s , covering a catchment area of 3.1 million inhabitants . A sample of 131 remitted first-episode patients , aged 18 to 45 years , with a DSM-IV diagnosis of schizophrenia or related psychotic disorder was included ( i.e. , all patients with a first psychotic episode from October 2001 through December 2002 who were willing to participate ) . After 6 months of positive symptom remission , they were r and omly and openly assigned to the discontinuation strategy or maintenance treatment . Maintenance treatment was carried out according to American Psychiatric Association guidelines , preferably using low-dose atypical antipsychotics . The discontinuation strategy was carried out by gradual symptom-guided tapering of dosage and discontinuation if feasible . Follow-up was 18 months . Main outcome measures were relapse rates and social and vocational functioning . RESULTS Twice as many relapses occurred with the discontinuation strategy ( 43 % vs. 21 % , p = .011 ) . Of patients who received the strategy , approximately 20 % were successfully discontinued . Recurrent symptoms caused another approximately 30 % to restart antipsychotic treatment , while in the remaining patients discontinuation was not feasible at all . There were no advantages of the discontinuation strategy regarding functional outcome . CONCLUSIONS Only a limited number of patients can be successfully discontinued . High relapse rates do not allow a discontinuation strategy to be universal practice . However , if relapse risk can be carefully managed by close monitoring , in some remitted first-episode patients a guided discontinuation strategy may offer a feasible alternative to maintenance treatment Output:	Antipsychotic treatment in patients with FEP produced high rates of remission in the year following treatment initiation , and untreated FEP reduced the odds of later achieving remission . Maintenance therapy was more effective than treatment discontinuation or intermittent/guided discontinuation in preventing relapse . Initiating antipsychotic treatment in patients with FEP also produced sustained cognitive improvement for up to 2 years . CONCLUSION Treatment of patients with FEP is associated with benefits in the long-term outcomes of remission , relapse , and cognition .
MS21899	*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: We here report nine liver cirrhosis ( LC ) patients that underwent autologous bone marrow cell infusion ( A BMI ) from the peripheral vein . Subjects were patients with LC with total bilirubin of less than 3.0 mg/dl , platelet count of more than 5 ( 10(10)/l ) , and no viable hepatocellular carcinoma on diagnostic imaging . Autologous bone marrow ( BM ; 400 ml ) was isolated from the ilium under general anesthesia . Mononuclear cells ( MNCs ) were separated by cell washing and were infused via the peripheral vein . MNC characteristics were confirmed by fluorescence-activated cell sorting analysis ( CD34 , CD45 , and c-kit ) . After A BMI therapy , liver function was monitored by blood examination for 24 weeks . From 400 ml of BM , we obtained 7.81 + /- 0.98 x 10(9 ) MNCs . After washing , 5.20 + /- 0.63 x 10(9 ) MNCs were infused into patients with LC . Significant improvements in serum albumin levels and total protein were observed at 24 weeks after A BMI therapy ( p < .05 ) . Significantly improved Child-Pugh scores were seen at 4 and 24 weeks ( p < .05 ) . alpha-Fetoprotein and proliferating cell nuclear antigen ( PCNA ) expression in liver biopsy tissue was significantly elevated after A BMI therapy ( p < .05 ) . No major adverse effects were noted . In conclusion , A BMI therapy should be considered as a novel treatment for patients with decompensated LC OBJECTIVES : Severe alcoholic hepatitis has high short-term mortality . The aim of this study was to test the hypothesis that treatment of patients with alcoholic hepatitis with granulocyte colony-stimulating factor ( G-CSF ) might mobilize bone marrow – derived stem cells and promote hepatic regeneration and thus improve survival . METHODS : Forty-six patients with severe alcoholic hepatitis were prospect ively r and omized in an open study to st and ard medical therapy ( SMT ) plus G-CSF ( group A ; n=23 ) at a dose of 5 μg/kg subcutaneously every 12 h for 5 consecutive days or to SMT alone ( group B ; n=23 ) at a tertiary care center . We assessed the mobilization of CD34 + cells on day 6 , Child-Turcotte-Pugh ( CTP ) , model for end-stage liver disease ( MELD ) , and modified Maddrey ’s discriminant function ( mDF ) scores , and survival until day 90 . RESULTS : There was a statistically significant increase in the number of CD34 + cells in peripheral blood in group A as compared with group B ( P=0.019 ) after 5 days of G-GSF therapy . There was a significant reduction in median Δ change% in CTP , MELD , and mDF at 1 , 2 , and 3 months in group A as compared with group B ( P<0.05 ) . There was marked improvement in survival in group A as compared with group B ( 78.3 % vs. 30.4 % ; P=0.001 ) at 90 days . CONCLUSIONS : G-CSF is safe and effective in the mobilization of hematopoietic stem cells and improves liver function as well as survival in patients with severe alcoholic hepatitis BACKGROUND Cirrhosis , the end stage of progressive hepatic fibrosis , is characterized by distortion of the hepatic architecture and the formation of regenerative nodules . Liver transplantation is one of the few available therapies for such patients . However , due to a severe shortage of organ donors , surgical complications , transplant rejection and the high cost of this procedure much interest has focused on research to find new treatment modalities for this disease . There is accumulating evidence for the contribution of bone marrow stem cells to participate in liver regeneration . METHODS Here we report on six patients with end stage liver disease who were subjected to intraportal administration of autologous bone marrow-derived CD133(+ ) in comparison to mononuclear cells in short-term ( 6 months ) and long-term ( 24 months ) follow up . RESULTS There were no adverse effects in any of the patients during the short- and long-term follow up period . Moreover , there were no significant alterations of liver function parameters , liver enzymes , serum albumin , creatinine , serum bilirubin and /or liver volume after transplantation of both types of autologous cells in these patients . CONCLUSION Our study has shown both the safety and feasibility of this type of liver cell therapy and may be a bridge to liver transplantation . The trial was registered with NIH clinical trials ( www . clinical trials.gov ) as identifier : NCT00713934 OBJECTIVES : Recent advances in regenerative medicine , including hematopoietic stem cell ( HSC ) transplantation , have brought hope for patients with severe alcoholic liver cirrhosis ( ALC ) . The aim of this study was to assess the safety and efficacy of administering autologous exp and ed mobilized adult progenitor CD34 + cells into the hepatic artery of ALC patients and the potential improvement in the liver function . METHODS : Nine patients with biopsy-proven ALC , who had abstained from alcohol for at least 6 months , were recruited into the study . Following granulocyte colony-stimulating factor ( G-CSF ) mobilization and leukapheresis , the autologous CD34 + cells were exp and ed in vitro and injected into the hepatic artery . All patients were monitored for side effects , toxicities , and changes in the clinical , hematological , and biochemical parameters . RESULTS : On average , a five-fold expansion in cell number was achieved in vitro , with a mean total nucleated cell count ( TNCC ) of 2.3 × 108 pre infusion . All patients tolerated the procedure well , and there were no treatment-related side effects or toxicities observed . There were significant decreases in serum bilirubin ( P < 0.05 ) 4 , 8 , and 12 wk post infusion . The levels of alanine transaminase ( ALT ) and aspartate transaminase ( AST ) showed improvement through the study period and were significant ( P < 0.05 ) 1 wk post infusion . The Child-Pugh score improved in 7 out of 9 patients , while 5 patients had improvement in ascites on imaging . CONCLUSION : It is safe to mobilize , exp and , and reinfuse autologous CD34 + cells in patients with ALC . The clinical and biochemical improvement in the study group is encouraging and warrants further clinical trials AIM To assess the utility of an autologous CD34(+ ) and CD133(+ ) stem cells infusion as a possible therapeutic modality in patients with end-stage liver diseases . METHODS One hundred and forty patients with end-stage liver diseases were r and omized into two groups . Group 1 , comprising 90 patients , received granulocyte colony stimulating factor for five days followed by autologous CD34(+ ) and CD133(+ ) stem cell infusion in the portal vein . Group 2 , comprising 50 patients , received regular liver treatment only and served as a control group . RESULTS Near normalization of liver enzymes and improvement in synthetic function were observed in 54.5 % of the group 1 patients ; 13.6 % of the patients showed stable states in the infused group . None of the patients in the control group showed improvement . No adverse effects were noted . CONCLUSION Our data showed that a CD34(+ ) and CD133(+ ) stem cells infusion can be used as supportive treatment for end-stage liver disease with satisfactory tolerability BACKGROUND / AIMS To evaluate feasibility , safety and pattern of bone marrow-derived cells ( BMC ) mobilization in patients with end stage liver cirrhosis following granulocyte-colony stimulating factor ( G-CSF ) administration . METHODS Eight patients with severe liver cirrhosis ( Child-Pugh score B-C , spleen diameter less than 170 mm ) were included . They were treated with G-CSF ( 5 microg/kg b.i.d for three consecutive days ) to mobilize BMC , evaluated as circulating CD34+ve cells ( flow cytometry ) and myeloid CFU-GM progenitors ( in vitro colony growth assay ) . Co-expression in CD34+ve cells markers of differentiation ( Thy1 , CD133 , CXCR4 , c1qRp ) were investigated on CD34+ve cells by double direct immunofluorescence . Data from 40 healthy haematopoietic stem cell donors were used as controls . RESULTS Mobilization of CD34+ve cells occurred in all patients . It was paralleled by expansion of circulating CFU-GM progenitors . Circulating CD34+ve cells co-expressed epithelial and stem cell markers in both cirrhotics and volunteer stem cell donors . G-CSF was well tolerated , no adverse event occurred , a significant reversible increase of splenic longitudinal diameter was observed . CONCLUSIONS ( i ) G-CSF mobilization of BMC co-expressing epithelial and stem markers occurred in all cirrhotic patients ; ( ii ) splenomegaly up to 170 mm does not prevent safe BMC mobilization following G-CSF in patients with end stage liver disease ; ( iii ) mobilized BMC may represent an easy immature cell source potentially useful for novel approaches for liver regeneration BACKGROUND & AIMS A consensus has been reached that liver donor allocation should be based primarily on liver disease severity and that waiting time should not be a major determining factor . Our aim was to assess the capability of the Model for End-Stage Liver Disease ( MELD ) score to correctly rank potential liver recipients according to their severity of liver disease and mortality risk on the OPTN liver waiting list . METHODS The MELD model predicts liver disease severity based on serum creatinine , serum total bilirubin , and INR and has been shown to be useful in predicting mortality in patients with compensated and decompensated cirrhosis . In this study , we prospect ively applied the MELD score to estimate 3-month mortality to 3437 adult liver transplant c and i date s with chronic liver disease who were added to the OPTN waiting list at 2A or 2B status between November , 1999 , and December , 2001 . RESULTS In this study cohort with chronic liver disease , 412 ( 12 % ) died during the 3-month follow-up period . Waiting list mortality increased directly in proportion to the listing MELD score . Patients having a MELD score < 9 experienced a 1.9 % mortality , whereas patients having a MELD score > or = 40 had a mortality rate of 71.3 % . Using the c-statistic with 3-month mortality as the end point , the area under the receiver operating characteristic ( ROC ) curve for the MELD score was 0.83 compared with 0.76 for the Child-Turcotte-Pugh ( CTP ) score ( P < 0.001 ) . CONCLUSIONS These data suggest that the MELD score is able to accurately predict 3-month mortality among patients with chronic liver disease on the liver waiting list and can be applied for allocation of donor livers AIM To evaluate safety and feasibility of autologous bone marrow-enriched CD34 + hematopoietic stem cell Tx through the hepatic artery in patients with decompensated cirrhosis . METHODS Four patients with decompensated cirrhosis were included . Approximately 200 mL of the bone marrow of the patients was aspirated , and CD34 + stem cells were selected . Between 3 to 10 million CD34 + cells were isolated . The cells were slowly infused through the hepatic artery of the patients . RESULTS Patient 1 showed marginal improvement in serum albumin and no significant changes in other test results . In patient 2 prothrombin time was decreased ; however , her total bilirubin , serum creatinine , and Model of End-Stage Liver Disease ( MELD ) score worsened at the end of follow up . In patient 3 there was improvement in serum albumin , porthrombin time ( PT ) , and MELD score . Patient 4 developed radiocontrast nephropathy after the procedure , and progressed to type 1 hepatorenal syndrome and died of liver failure a few days later . Because of the major side effects seen in the last patient , the trial was prematurely stopped . CONCLUSION Infusion of CD34 + stem cells through the hepatic artery is not safe in decompensated cirrhosis . Radiocontrast nephropathy and hepatorenal syndrome could be major side effects . However , this study does not preclude infusion of CD34 + stem cells through other routes Output:	Discussion This systematic review will identify the available evidence on the effectiveness of cell therapies in patients with CLD and in ACLF subgroup .

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