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MS2700	*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 Chronic obstructive pulmonary disease ( COPD ) remains a significant public health burden . Non-invasive ventilation ( NIV ) is a method of supported breathing used as st and ard care for acutely unwell patients in hospital with COPD , but there is uncertainty around the potential benefits of using NIV in the treatment of stable patients in a non-hospital setting . This is a protocol for systematic review s of the clinical and cost-effectiveness of NIV in this context , being undertaken in support of a model based economic evaluation . Methods / Design St and ard systematic review methods aim ed at minimising bias will be employed for study identification , selection and data extraction for both the clinical and economic systematic review s. Bibliographic data bases ( for example MEDLINE , EMBASE ) and ongoing trials registers will be search ed from 1980 onwards . The search strategy will combine terms for the population with those for the intervention . Studies will be selected for review if the population includes adult patients with COPD and hypercapnic respiratory failure , however defined . Systematic review s , r and omised controlled trials and observational studies ( with n > 1 ) will be included , and quality assessment will be tailored to the different study design s. The primary outcome measures of interest are survival , quality of life , and healthcare utilisations ( hospitalisation and Accident and Emergency attendances ) . Meta-analyses will be undertaken where clinical and method ological homogeneity exists , supported by predefined subgroup analyses where appropriate . A systematic review of the evidence on the cost-effectiveness of non-hospital NIV will be completed , and a model-based cost-utility analysis undertaken to determine the cost-effectiveness of non-hospital-based NIV compared with st and ard care . Discussion These review s will attempt to clarify the clinical effectiveness of non-hospital NIV in COPD patients as well as the cost-effectiveness . The findings may indicate whether NIV in a non-hospital setting should be considered more routinely in this patient group , and what the likely cost implication s will be . PROSPERO registration 2012:CRD42012003286 Background Exacerbations of chronic obstructive pulmonary disease ( COPD ) are sporadic , acute worsening of symptoms . Identifying predictors of exacerbation frequency may facilitate medical interventions that reduce exacerbation frequency and severity . The objective of this study was to determine predictors of exacerbation frequency and mortality . Methods A total of 227 COPD patients were enrolled in a prospect i ve clinical study between January 2000 and December 2011 . Reported exacerbations were recorded for the year preceding enrollment and annually thereafter , and patients were grouped by median annual exacerbation frequency into those experiencing infrequent exacerbations ( less than one exacerbation annually ) and frequent exacerbations ( one or more exacerbation annually ) . Patients experiencing frequent exacerbations were further divided into those experiencing moderately frequent exacerbations ( fewer than two exacerbations per year ) and severely frequent exacerbations ( two or more exacerbations per year ) . The rate of clinical relapse and survival was recorded over a 10-year period . The mean of follow-up time was 5.15 years per patient . Results For patients experiencing infrequent , moderately frequent , and severely frequent exacerbations , median exacerbations in the year preceding enrollment were 0.0 , 0.5 , 1.0 , respectively , and more frequent exacerbations correlated with lower baseline forced expiratory volume in one second ( FEV1 ) ( 0.81 L , 0.75 L , and 0.66 L , respectively ) , higher comorbidity ( 70.7 % , 75.0 % , and 89.4 % , respectively ) , and greater NPPV use during hospitalization ( 16.4 % , 35.9 % and 51.1 % , respectively ) . FEV1 declined and mortality increased with increasing exacerbation frequency . Conclusions Exacerbation frequency can be used to generate discreet patient sub population s , supporting the hypothesis that multiple COPD phenotypes exist and can be used in patient risk stratification Background : Long-term non-invasive positive pressure ventilation ( NIPPV ) might improve the outcomes of pulmonary rehabilitation in patients with chronic obstructive pulmonary disease ( COPD ) with chronic respiratory failure . A study was undertaken to investigate whether nocturnal NIPPV in addition to pulmonary rehabilitation improves health-related quality of life , functional status and gas exchange compared with pulmonary rehabilitation alone in patients with COPD with chronic hypercapnic respiratory failure . Methods : 72 patients with COPD were r and omly assigned to nocturnal NIPPV in addition to rehabilitation ( n = 37 ) or rehabilitation alone ( n = 35 ) . Outcome measures were assessed before and after the 3-month intervention period . Results : The Chronic Respiratory Question naire total score improved 15.1 points with NIPPV + rehabilitation compared with 8.7 points with rehabilitation alone . The difference of 7.5 points was not significant ( p = 0.08 ) . However , compared with rehabilitation alone , the difference in the fatigue domain was greater with NIPPV + rehabilitation ( mean difference 3.3 points , p<0.01 ) , as was the improvement in the Maugeri Respiratory Failure question naire total score ( mean difference −10 % , p<0.03 ) and its cognition domain ( mean difference −22 % , p<0.01 ) . Furthermore , the addition of NIPPV improved daytime arterial carbon dioxide pressure ( mean difference −0.3 kPa ; p<0.01 ) and daily step count ( mean difference 1269 steps/day , p<0.01 ) . This was accompanied by an increased daytime minute ventilation ( mean difference 1.4 l ; p<0.001 ) . Conclusion : Non-invasive ventilation augments the benefits of pulmonary rehabilitation in patients with COPD with chronic hypercapnic respiratory failure as it improves several measures of health-related quality of life , functional status and gas exchange . Trial registration number : NCT00135538 Introduction Noninvasive ventilation ( NIV ) is a well-established treatment for acute-on- chronic respiratory failure in hypercapnic COPD patients . Less is known about the effects of a long-term treatment with NIV in hypercapnic COPD patients and about the factors that may predict response in terms of improved oxygenation and lowered CO2 retention . Methods In this study , we r and omized 15 patients to a routine pharmacological treatment ( n = 5 , age 66 [ st and ard deviation ± 6 ] years , FEV1 30.5 [ ±5.1 ] % pred , PaO2 65 [ ±6 ] mmHg , PaCO2 52.4 [ ±6.0 ] mmHg ) or to a routine treatment and NIV ( using the Synchrony BiPAP device [ Respironics , Inc , Murrsville , PA ] ) ( n = 10 , age 65 [ ±7 ] years , FEV1 29.5 [ ±9.0 ] % pred , PaO2 59 [ ±13 ] mmHg , PaCO2 55.4 [ ±7.7 ] mmHg ) for 6 months . We looked at arterial blood gasses , lung function parameters and performed a low-dose computed tomography of the thorax , which was later used for segmentation ( providing lobe and airway volumes , iVlobe and iVaw ) and post-processing with computer methods ( providing airway resistance , iRaw ) giving overall a functional image of the separate airways and lobes . Results In both groups there was a nonsignificant change in FEV1 ( NIV group 29.5 [ 9.0 ] to 38.5 [ 14.6 ] % pred , control group 30.5 [ 5.1 ] to 36.8 [ 8.7 ] mmHg ) . PaCO2 dropped significantly only in the NIV group ( NIV : 55.4 [ 7.7 ] → 44.5 [ 4.70 ] , P = 0.0076 ; control : 52.4 [ 6.0 ] → 47.6 [ 8.2 ] , NS ) . Patients actively treated with NIV developed a more inhomogeneous redistribution of mass flow than control patients . Subsequent analysis indicated that in NIV-treated patients that improve their blood gases , mass flow was also redistributed towards areas with higher vessel density and less emphysema , indicating that flow was redistributed towards areas with better perfusion . There was a highly significant correlation between the % increase in mass flow towards lobes with a blood vessel density of > 9 % and the increase in PaO2 . Improved ventilation – perfusion match and recruitment of previously occluded small airways can explain the improvement in blood gases . Conclusion We can conclude that in hypercapnic COPD patients treated with long-term NIV over 6 months , a mass flow redistribution occurs , providing a better ventilation – perfusion match and hence better blood gases and lung function . Control patients improve homogeneously in iVaw and iRaw , without improvement in gas exchange since there is no improved ventilation/perfusion ratio or increased alveolar ventilation . These differences in response can be detected through functional imaging , which gives a more detailed report on regional lung volumes and resistances than classical lung function tests do . Possibly only patients with localized small airway disease are good c and i date s for long-term NIV treatment . To confirm this and to see if better arterial blood gases also lead to better health related quality of life and longer survival , we have to study a larger population Background : Sleep hypoventilation has been proposed as a cause of progressive hypercapnic respiratory failure and death in patients with severe chronic obstructive pulmonary disease ( COPD ) . A study was undertaken to determine the effects of nocturnal non-invasive bi-level pressure support ventilation ( NIV ) on survival , lung function and quality of life in patients with severe hypercapnic COPD . Method : A multicentre , open-label , r and omised controlled trial of NIV plus long-term oxygen therapy ( LTOT ) versus LTOT alone was performed in four Australian University Hospital sleep/respiratory medicine departments in patients with severe stable smoking-related COPD ( forced expiratory volume in 1 s ( FEV1.0 ) < 1.5 litres or < 50 % predicted and ratio of FEV1.0 to forced vital capacity ( FVC ) < 60 % with awake arterial carbon dioxide tension ( Paco2 ) > 46 mm Hg and on LTOT for at least 3 months ) and age < 80 years . Patients with sleep apnoea ( apnoea-hypopnoea index > 20/h ) or morbid obesity ( body mass index > 40 ) were excluded . Outcome measures were survival , spirometry , arterial blood gases , polysomnography , general and disease-specific quality of life and mood . Results : 144 patients were r and omised ( 72 to NIV + LTOT and 72 to LTOT alone ) . NIV improved sleep quality and sleep-related hypercapnia acutely , and patients complied well with therapy ( mean ( SD ) nightly use 4.5 ( 3.2 ) h ) . Compared with LTOT alone , NIV ( mean follow-up 2.21 years , range 0.01–5.59 ) showed an improvement in survival with the adjusted but not the unadjusted Cox model ( adjusted hazard ratio ( HR ) 0.63 , 95 % CI 0.40 to 0.99 , p = 0.045 ; unadjusted HR 0.82 , 95 % CI 0.53 to 1.25 , p = NS ) . FEV1.0 and Paco2 measured at 6 and 12 months were not different between groups . Patients assigned to NIV + LTOT had reduced general and mental health and vigour . Conclusions : Nocturnal NIV in stable oxygen-dependent patients with hypercapnic COPD may improve survival , but this appears to be at the cost of worsening quality of life . Trial registration number : The role of non-invasive nocturnal domiciliary ventilation ( NNV ) in chronic obstructive pulmonary disease ( COPD ) patients with chronic hypercapnia is still discussed . The aims of this study were to evaluate the long-term survival , the clinical effectiveness and side-effects of NNV in these patients . Forty-nine stable hypercapnic COPD patients on long-term oxygen therapy ( LTOT ) were assigned to two groups : in Group 1 , 28 patients performed NNV by pressure support modality in addition to LTOT ; in Group 2 , 21 patients continued their usual LTOT regimen . Treatment was assigned according to the compliance to NNV , after an in hospital period . Mortality rate , hospital stay ( HS ) and ICU admissions ( IA ) were recorded in the two groups . HS and IA were compared to those recorded in a similar period of follow-back . Lung and respiratory muscle function , dyspnoea , and exercise capacity ( by 6-min walk test ) were evaluated baseline and every 3 - 6 months up to 3 yr . Mean follow-up time was 35 + /- 7 months . Mortality rate was not different between the two groups : 16 , 33 , 46 % and 13 , 28 , 50 % at 1 , 2 and 3 yr in Groups 1 and 2 respectively . Lung and respiratory muscle function did not significantly change over time . A significant increase in 6-min walk test ( from 245 + /- 78 to 250 + /- 88 , 291 + /- 75 , 284 + /- 89 m after 1 , 2 and 3 yr respectively , P < 0.01 ) was observed only in Output:	CONCLUSION The effectiveness of domiciliary NIV remains uncertain ; however , some patients may benefit .
MS2701	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Aims : To provide a comprehensive description of young infant admissions to a first referral level health facility in Kenya . These data , currently lacking , are important given present efforts to st and ardise their care through the integrated management of childhood illness ( IMCI ) and for prioritising both health care provision and disease prevention strategies . Methods : Prospect i ve , 18 month observational study in a Kenyan district hospital of all admissions less than 3 months of age to the paediatric ward . Results : A total of 1080 infants were studied . Mortality was 18 % overall , though in those aged 0–7 days it was 34 % . Within two months of discharge a further 5 % of infants aged < 60 days on admission had died . Severe infection and prematurity together accounted for 57 % of inpatient deaths in those aged < 60 days , while jaundice and tetanus accounted for another 27 % . S pneumoniae , group B streptococcus , E coli , and Klebsiella spp . were the most common causes of invasive bacterial disease . Hypoxaemia , hypoglycaemia , and an inability to feed were each present in more than 20 % of infants aged 0–7 days . Both hypoxaemia and the inability to feed were associated with inpatient death ( OR 3.8 ( 95 % CI 2.5 to 5.8 ) and 7.4 ( 95 % CI 4.8 to 11.2 ) respectively ) . Conclusions : Young infants contribute substantially to paediatric inpatient mortality at the first referral level , highlighting the need both for basic supportive care facilities and improved disease prevention strategies OBJECTIVES To quantify the main reasons for referral of infants and children from first-level health facilities to referral hospitals in sub-Saharan Africa and to determine what further supplies , equipment , and legal empowerment might be needed to manage such children when referral is difficult . METHODS In an observational study at first-level health facilities in Ug and a , the United Republic of Tanzania , and Niger , over 3 - 5 months , we prospect ively documented the diagnoses and severity of diseases in children using the st and ardized Integrated Management of Childhood Illness ( IMCI ) guidelines . We review ed the facilities for supplies and equipment and examined the legal constraints of health personnel working at these facilities . FINDINGS We studied 7195 children aged 2 - 59 months , of whom 691 ( 9.6 % ) were classified under a severe IMCI classification that required urgent referral to a hospital . Overall , 226 children had general danger signs , 292 had severe pneumonia or very severe disease , 104 were severely dehydrated , 31 had severe persistent diarrhoea , 207 were severely malnourished , and 98 had severe anaemia . Considerably more ill were 415 young infants aged one week to two months : nearly three-quarters of these required referral . Legal constraints and a lack of simple equipment ( suction pumps , nebulizers , and oxygen concentrators ) and supplies ( nasogastric tubes and 50 % glucose ) could prevent health workers from dealing more appropriately with sick children when referral was not possible . CONCLUSION When referral is difficult or impossible , some additional supplies and equipment , as well as provision of simple guidelines , may improve management of seriously ill infants and children OBJECTIVE to estimate the prevalence and identify the determinants of non-prescription use of antibiotics for children in Mongolia . METHODS a community-based cross-sectional survey was undertaken in 10 subdistricts in Ulaanbaatar , Mongolia 's capital . We used a structured question naire to collect data from a r and om sample of 540 households with at least one child aged < 5 years . Logistic regression was used to identify factors associated with antibiotic misuse . FINDINGS of 503 participating caregivers , 71 % were mothers ; 42.3 % ( 95 % confidence interval , CI : 37.8 - 46.9 ) of caregivers had used non-prescribed antibiotics to treat symptoms in their child during the previous 6 months . Symptoms commonly treated were cough ( 84 % ) , fever ( 66 % ) , nasal discharge ( 65 % ) and sore throat ( 60 % ) . Amoxicillin was the most commonly used antibiotic ( 58 % ) . Pharmacies were the main source ( 86 % ) of non-prescribed antibiotics . Non-prescribed use by mothers was significantly associated with keeping antibiotics at home ( odds ratio , OR : 1.7 ; 95 % CI : 1.04 - 2.79 ) , caregiver self-medication ( OR : 6.3 ; 95 % CI : 3.8 - 10.5 ) and older child 's age ( OR : 1.02 ; 95 % CI : 1.01 - 1.04 ) . Caregivers with a better knowledge of antibiotics were less likely to give children non-prescribed antibiotics ( OR : 0.7 ; 95 % CI : 0.6 - 0.8 ) . CONCLUSION the prevalence of non-prescribed antibiotic use for young children was high in Ulaanbaatar . Because such use leads to the spread of bacterial resistance to antibiotics and related health problems , our findings have important implication s for public education and the enforcement of regulations regarding the sale of antibiotics in Mongolia Background : In re source -limited setting s , most young infants with signs of severe infection do not receive the recommended inpatient treatment with intravenous broad spectrum antibiotics for 10 days or more because such treatment is not accessible , acceptable or affordable to families . This trial was initiated in the Democratic Republic of Congo , Kenya and Nigeria to assess the safety and efficacy of simplified treatment regimens for the young infants with signs of severe infection who can not receive hospital care . Methods : This is a r and omized , open-label equivalence trial in which 3600 young infants with signs of clinical severe infection will be enrolled . The primary outcome is treatment failure in 7 days after enrollment , which includes death or worsening of the clinical condition on any day , or no improvement in the clinical condition by day 4 of treatment . Secondary outcomes include compliance with study therapy , adverse effects due to the study drugs and relapse or death during the week after completion of treatment . Discussion : The results of this study , along with ongoing studies in Pakistan and Bangladesh , will inform the development of global policy for treatment of severe neonatal infections in re source -limited setting OBJECTIVE Little data has been published on the presenting symptoms and signs among ill infants aged < 60 days from developing countries . We aim ed to describe and evaluate the potential of simple clinical features to identify severe illness among young infants who present to rural district hospitals in Kenya . METHODS St and ardized assessment tools were design ed to record clinical symptoms and signs . Data were collected prospect ively on all infants aged < 60 days who weighed > or = 1.5 kg and were admitted over an 18-month period . The same data were collected , prospect ively from infants recruited to a contemporaneous hospital birth cohort who became ill and were assessed and treated as out patients at the same hospital . FINDINGS Data on 467 outpatient consultations and 769 inpatient episodes were available for analysis . These data highlighted the importance of findings in the history , particularly breathing difficulties , abnormal feeding , and abnormal behaviour , as well as clinical signs in the evaluation of young infants . They indicated possible important differences in the panel of signs useful for detecting severe illness in infants aged 0 - 6 days and those aged 7 - 59 days . They also showed that some simplification of current guidelines that still preserved the sensitivity and specificity for detecting very severe disease might be possible . CONCLUSION Simple clinical features may allow distinction between severe and non-severe illness to be made with reasonable confidence . Prospect i ve studies on an adequate scale are needed urgently to provide current integrated management of childhood illness guidelines for young infants with an adequate evidence base To determine the effect of antibiotic formulations on compliance , 400 children , aged 2 months to 5 years , with a presumptive diagnosis of pneumonia , were r and omly assigned to receive one of the following formulations of cotrimoxazole : 1 . syrup accompanied by a 10-ml measuring cup ; 2 . syrup accompanied by a 5-ml measuring spoon ; 3 . tablets ; 4 . single-dose sachets of antibiotic powder . A research assistant visited the childs ' home on the fourth day of therapy , asked the care-giver about compliance , and observed the care-giver prepare a dose of the medication . The remaining amount of medicine was measured , and when possible ( n = 151 ) , a urine specimen was tested for the presence of sulphamethoxazole . All of the care-givers reported giving at least one dose on the first day of therapy . By the fourth day , 82 per cent of those receiving syrup were still taking their medication compared to 71 and 55 per cent of those receiving sachets or tablets , respectively ( P < 0.01 ) . Of those who received syrup accompanied by a spoon , 38 per cent under-dosed the medicine by at least 30 per cent . Overall , compliance was highly correlated with the care-giver 's report of difficulty in administering the medication . Additional research is needed to underst and the obstacles encountered by care-givers in administering sachets and tablets . Meanwhile , the use of antibiotic syrup , accompanied by an appropriately sized measuring cup , appears to offer the greatest probability of medication compliance in the treatment of Egyptian children with pneumonia Objective To check the validity of Integrated Management of Neonatal and Childhood Illness ( IMNCI ) algorithm for young infants ( 0–2 months ) . Design Prospect i ve observational study . Setting The outpatient department and emergency room of a medical college attached hospital . Methods 419 infants ( 176 between 0–7 days , 243 between 7 days-2 months ) underwent a detailed diagnostic assessment and treatment as per the st and ard protocol of treating unit . These infants also underwent assessment , classification and identification of treatment as per IMNCI algorithm . The diagnostic and therapeutic agreement between st and ard protocol and IMNCI was computed to assess the validity of IMNCI algorithm . Results The IMNCI algorithm performed well in identifying sick young infants with sensitivity of 97 % , 94 % and 95 % , and specificity of 85 % , 87 % and 87 % in 0–7 days , 7 days-2 months and 0–2 months age groups , respectively . The algorithm covered majority ( 80 % ) of recorded diagnoses , and could identify bacterial infection with 88.5 % sensitivity and 57.4 % specificity . Complete diagnostic agreement with gold st and ard was seen in 50 % ; overdiagnosis and under diagnosis was seen in 13 % and 19 % , respectively . Low birthweight and upper respiratory infection were the main reasons for overdiagnosis whereas surgical conditions result ed in under diagnoses in majority . Conclusion IMNCI algorithm for evaluation and management of young infants has good sensitivity and specificity for referring cases with severe illness Antibiotics are utilized excessively in many areas of the world . To better define how often and why these drugs are used , we prospect ively studied antibiotic use among a cohort of 105 children less than five years of age in a poor area of the northeastern Brazilian city of Fortaleza . During a 16-week period , 65 children took 137 courses of antibiotics . Physicians recommended 54 % of these , mothers or their associates 39 % , and pharmacy workers 7 % . Mothers and pharmacy workers recommended drugs for shorter courses than physicians , and were more likely to recommend drugs inappropriate for children . Duration of illness was not a risk factor for antibiotic use , but both poor nutritional status and poor socioeconomic status were . Health care seeking behaviour was further studied in 58 diarrhoea episodes . The type of care sought was related to the duration of illness . Overall , antibiotic use was very common and often inappropriate among children in this poor urban area . More controlled use might decrease the use of potentially dangerous drugs and the use of these drugs when no benefit is likely BACKGROUND About 500,000 sepsis-related deaths per year arise in the first 3 days of life . On the basis of results from non-r and omised studies , use of vaginal chlorhexidine wipes during labour has been proposed as an intervention for the prevention of early-onset neonatal sepsis in developing countries . We therefore assessed the efficacy of chlorhexidine in early-onset neonatal sepsis and vertical transmission of group B streptococcus . METHODS In a trial in Soweto , South Africa , 8011 women ( aged 12 - 51 years ) were r and omly assigned in a 1:1 ratio to chlorhexidine vaginal wipes or external genitalia water wipes during active labour , and their 8129 newborn babies were assigned to full-body ( intervention group ) or foot ( control group ) washes with chlorhexidine at birth , respectively . In a subset of mothers ( n=5144 ) , we gathered maternal lower vaginal swabs and neonatal skin swabs after delivery to assess colonisation with potentially pathogenic bacteria . Primary outcomes were neonatal sepsis in the first 3 days of life and vertical transmission of group B streptococcus . Analysis was by intention to treat . The trial is registered with Clinical Trials.gov , number NCT00136370 . FINDINGS Rates of neonatal sepsis did not differ between the groups ( chlorhexidine 141 [ 3 % ] of 4072 vs control Output:	For question 2 , first-line injectable agents ( ampicillin , gentamicin , and penicillin ) had low variable availability in first-level health facilities in Africa and South Asia . Oral amoxicillin and cotrimoxazole were widely available at low cost in most regions . Trained frontline health workers may screen for pBI in young infants with relatively high sensitivity and lower specificity . Availability of first-line injectable antibiotics appears low in many health facilities in Africa and Asia .
MS2702	*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: Therapeutic hypothermia holds promise as a rescue neuroprotective strategy for hypoxic-ischemic injury , but the incidence of severe neurologic sequelae with hypothermia is unknown in encephalopathic neonates who present shortly after birth . This study reports a multicenter , r and omized , controlled , pilot trial of moderate systemic hypothermia ( 33 degrees C ) vs normothermia ( 37 degrees C ) for 48 hours in neonates initiated within 6 hours of birth or hypoxic-ischemic event . The trial tested the ability to initiate systemic hypothermia in outlying hospitals and participating tertiary care centers , and determined the incidence of adverse neurologic outcomes of death and developmental scores at 12 months by Bayley II or Vinel and tests between normothermic and hypothermic groups . Thirty-two hypothermic and 33 normothermic neonates were enrolled . The entry criteria selected a severely affected group of neonates , with 77 % Sarnat stage III . Ten hypothermia ( 10/32 , 31 % ) and 14 normothermia ( 14/33 , 42 % ) patients expired . Controlling for treatment group , outborn infants were significantly more likely to die than hypoxic-ischemic infants born in participating tertiary care centers ( odds ratio 10.7 , 95 % confidence interval 1.3 - 90 ) . Severely abnormal motor scores ( Psychomotor Development Index < 70 ) were recorded in 64 % of normothermia patients and in 24 % of hypothermia patients . The combined outcome of death or severe motor scores yielded fewer bad outcomes in the hypothermia group ( 52 % ) than the normothermia group ( 84 % ) ( P = 0.019 ) . Although these results need to be vali date d in a large clinical trial , this pilot trial provides important data for clinical trial design of hypothermia treatment in neonatal hypoxic-ischemic injury OBJECTIVE To assess the safety of selective head cooling in birth-asphyxiated term newborn infants while maintaining the rectal temperature at 35.0 degrees C or 34.5 degrees C. METHODS Twenty-six term infants with Apgar < or=6 at 5 minutes or cord/first arterial pH < 7.1 , plus evidence of encephalopathy , were studied . After parental consent had been obtained , 13 infants received selective head cooling with the rectal temperature maintained at 35.0 degrees C in 6 infants and at 34.5 degrees C in 7 infants . The remaining 13 infants were normothermic . Cooling was achieved by circulating water at 10 degrees C through a cap placed around the head . Rectal , fontanelle , and nasopharyngeal temperatures were monitored . RESULTS One cooled infant died 2 days after rewarming , and 3 control infants died . Seizures occurred in 9 (69%)of 13 cooled infants and 5 ( 38 % ) of 13 control infants . Respiratory support within the first 72 hours of life was required in 10 of 13 infants in both the cooled and control groups . Three cooled infants and 1 control infant received nitric oxide for persistent pulmonary hypertension . During the same interval , 6 of the cooled infants and 4 of the control infants had episodes in which their blood pressure fell to < 40 mm Hg ; in 2 infants in each group , the lowest blood pressure was below 35 mm Hg . No requirement for volume expansion or increased inotropic support was seen in any infant during stepwise rewarming . All of the cooled infants demonstrated a fall in heart rate during cooling , but the rate was < 80/min in only 2 cases and no infant had a rate < 70/min . No infant demonstrated an abnormal rhythm or was clinical ly compromised by the change in heart rate . One infant cooled to a rectal temperature of 34.5 degrees C had a prolonged QT interval of 570 ms associated with a heart rate of 85/min on electrocardiogram aged 34 hours . This returned to normal after rewarming . Platelet counts below 150 x 10(9)/L , hypoglycemia below 2.6 mmol/L , and highest creatinine were not statistically different between cooled and control infants . Positive precooling blood cultures were found in 1 cooled and 1 control infant . The mean cap water input temperature used during cooling was 10 + /- 1 degrees C. During active cooling , the mean difference between rectal and nasopharyngeal temperature was 1.4 degrees C in the infants who were not receiving respiratory support , but this gradient could not be measured in those who were receiving respiratory support that involved delivery of warmed gases to the nasopharynx . CONCLUSIONS This study suggests that selective head cooling combined with mild systemic hypothermia of 34.4 degrees C or 35.0 degrees C is a stable , well-tolerated method of reducing cerebral temperature in term newborn infants after perinatal asphyxia In order to test the practicability and safety of whole-body cooling in term neonates with moderate-to-severe hypoxic-ischaemic encephalopathy ( HIE ) and to report outcomes , a prospect i ve pilot study was carried out in 25 term infants ( median postmenstrual age 38 weeks , range 36 to 41 weeks ; 20 males , five females ) . Whole-body cooling , to a target core temperature of 33 to 34 degrees C , started within 6 hours of birth and was maintained for 72 hours . Of the 25 newborn infants ( 19 Sarnat II and six Sarnat III , 18 outborn ) , 18 survived , including 13 ( 72 % ) with normal cerebral signal by MRI . Temperature instability occurred during cooling in 15 infants , but neither severe haemodynamic instability nor renal failure was seen . Thrombocytopenia developed in 12 infants , including seven with biological disseminated intravascular coagulation . One patient had hypoxaemia with right-to-left shunting through the ductus arteriosus , and seven had limited meningeal or subdural bleeding . Whole-body cooling is feasible in term neonates , with no life-threatening adverse events . Improvements are needed to obtain stable hypothermia for 72 hours Hypoxic-ischemic encephalopathy ( HIE ) remains one of the most important neurologic complications in the newborn . Several experimental and clinical studies have shown that hypothermia is the most effective means known for protecting the brain against hypoxic-ischemic brain damage . Furthermore , recent data have suggested that platelet-activating factor ( PAF ) could play a pathophysiologically important role in the progression of hypoxic-ischemic brain injury . The aim of the present study was to investigate the role of head cooling combined with minimal hypothermia in short-term outcome of infants with perinatal asphyxia . In addition , we have examined the effect of head cooling combined with minimal hypothermia on PAF concentrations in cerebrospinal fluid ( CSF ) after hypoxic-ischemic brain injury . The group of asphyxiated infants ( Group 1 ) consisted of 21 full-term ( gestational age > 37 weeks ) . These infants were r and omized and divided into either a st and ard therapy group ( Group 1a ; n=10 ) or cooling group ( Group 1b ; n=11 ) . Head cooling combined with minimal hypothermia ( rectal temperature 36.5 - 36 degrees C ) was started as soon as practicable after birth . The infants were cooled for 72h and then were rewarmed at 0.5 degrees C/h . The control group ( Group 2 ) consisted of seven full-term infants and none of these infants showed any sign of asphyxia . To measure PAF concentration in CSF , CSF with lumbar puncture was collected into tubes immediately before the cooling ( 1 - 3h after birth ) and again after 36h . We had no evidence of severe adverse events related to hypothermia . In Group 1a , two infants died after 72h of life ; however , all newborn infants in Group 1b survived . Convulsion required treatment in three infants of st and ard therapy group ( 1a ) ; none of the infants in Group 1b had clinical seizure activity . Abnormal EEG patterns were found in four infants of Group 1a ; no EEG abnormalities were noted in Group 1b ( P<0.05 ) . On admission ( before cooling ) , PAF concentration in CSF of asphyxiated infants was found to be significantly higher when compared with that of control ( P<0.001 ) . Mean PAF concentration before initiation of the study was similar in the two asphyxiated groups ( Group 1a vs. 1b ) ( P>0.05 ) . Obtained PAF level in CSF after 36h , showed a profound decline in cooling group of infants compared to Group 1a infants ( P<0.01 ) . In conclusion , the present study suggests that cerebral cooling with minimal hypothermia started soon after birth has no severe adverse effects during 72-h cooling period and that short-term outcome of infants are encouraging . Our results also support the hypothesis PAF an important mediator in hypoxic-ischemic brain injury and demonstrate that head cooling combined with minimal hypothermia reduces the normal increase in PAF following hypoxic-ischemic brain injury in full-term infants Twenty-six infants with hypoxic-ischemic encephalopathy ( HIE ) were r and omized to normothermia or to systemic hypothermia . The hypothermia group had less cortical gray matter signal abnormality on magnetic resonance imaging ( MRI ) ( 1/12 vs 7/14 infants in the normothermic group ; P = .036 ) , which may indicate differing regional benefit from systemic hypothermia Background . There is extensive experimental evidence to support the investigation of treatment with mild hypothermia after birth asphyxia . However , clinical studies have been delayed by the difficulty in predicting long-term outcome very soon after birth and by concern about adverse effects of hypothermia . Objectives . The objectives of this study were to determine whether it is feasible to select infants with a bad neurological prognosis and to begin hypothermic therapy within 6 hours of birth , and to observe the effect of this therapy on relevant physiologic variables . Methods . Sixteen newborn infants with clinical features of birth asphyxia ( median cord blood pH : 6.74 ; range : 6.58–7.08 ) were assessed by amplitude integrated electroencephalography ( aEEG ) , and mild whole body hypothermia was instituted within 6 hours of birth in the 10 infants with an aEEG prognostic of a bad outcome . Rectal temperature was maintained at 33.2 ± ( st and ard deviation ) .6 ° C for 48 hours . Rectal and tympanic membrane temperature , blood pressure , heart rate , blood gases , blood lactate , full blood count , blood electrolytes , high and low shear rate viscosity , and coagulation studies were monitored during and after cooling . A preliminary assessment of neurological outcome was made by repeated magnetic resonance imaging ( MRI ) and neurological examination . Results . All infants selected to receive hypothermia developed convulsions and a severe encephalopathy . During 48 hours of hypothermia infants had prolonged metabolic acidosis ( median pH : 7.30 ; base excess : −6.3 mmol · L− 1 , a high blood lactate ( median lactate : 5.3 mmol · L− 1 ) and low blood potassium levels ( median value : 3.9 mmol · L− 1 ) . Hypothermia was associated with lower heart rate and higher mean blood pressure . However , these changes did not seem to be clinical ly relevant and no significant complication of hypothermia was encountered . Blood viscosity and coagulation studies were similar during and after cooling . Unusual MRI findings were noted in 3 infants : transverse sinus thrombosis with subsequent small cerebellar infa rct ; probable thrombosis in the straight sinus ; and hemorrhagic cerebral infa rct ion . Six of the 10 cooled infants had minor abnormalities only or normal follow-up neurological examination ; 3 infants died and 1 had major abnormalities . None of the 6 infants with a normal aEEG developed severe neonatal encephalopathy or neurological sequel . Conclusions . After birth asphyxia infants can be objective ly selected by aEEG and hypothermia started within 6 hours of birth in infants at high risk of developing severe neonatal encephalopathy . Prolonged mild hypothermia to 33 ° C to 34 ° C is associated with minor physiologic abnormalities . Further studies of both the safety and efficacy of mild hypothermia , including further neuroimaging studies , are warranted Aims . To determine the practicality and safety of head cooling with mild or minimal systemic hypothermia in term neonates with moderate to severe hypoxic-ischemic encephalopathy . Methods . Study group infants ≥37 weeks ' gestation , who had an umbilical artery pH ≤7.09 or Apgars ≤6 at 5 minutes , plus evidence of encephalopathy . Infants with major congenital abnormalities were excluded . Trial Design . Infants were r and omized to either no cooling ( controls ; rectal temperature = 37.0 ± 0.2 ° C , n = 10 ) or sequentially , either minimal systemic cooling ( rectal temperature = 36.3 ± 0.2 ° C , n = 6 ) or mild systemic cooling ( rectal temperature = Output:	Cardiac arrhythmias and thrombocytopenia were more common with hypothermia ; however , they were clinical ly benign . In neonates with postintrapartum asphyxial hypoxic-ischemic encephalopathy , hypothermia is effective in reducing death and moderate to severe neurodevelopmental disability either in combination or separately and is a safe intervention
MS2703	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The aim of this study of the present experiment was to study the marginal periimplant tissues at intentionally non-submerged ( 1-stage implants ) and initially submerged and subsequently exposed implants ( 2-stage implants ) . 5 beagle dogs , about 1-year-old , were used , 3 months after the extraction of the m and ibular premolars , fixtures of the Astra Tech Implants Dental System , the Brånemark System and the Bonefit -- ITI system were installed . In each m and ibular quadrant , 1 fixture of each implant system was installed in a r and omised order . The installation procedure followed the recommendations given in the manuals for each system . Thus , following installation , the bone crest coincided with the fixture margin of the Astra Tech Implants Dental System and the Brånemark System , whereas the border between the plasma sprayed and the machined surface of the Bonefit-ITI implant system was positioned at the level of the bone crest . Following a healing period of 3 months , abutment connection was carried out in the 2-stage systems ( the Astra Tech Implants Dental System and the Brånemark system ) . A 6-month period of plaque control was initiated . The animals were sacrificed and biopsies representing each important region dissected . The tissue sample s were prepared for light microscopy and exposed to histometric and morphometric measurements . The mucosal barrier which formed to the titanium surface following 1-stage and 2-stage implant installations comprised an epithelial and a connective tissue component , which for that 3 systems studied , had similar dimensions and composition . The amount of lamellar bone contained in the periimplant region close to the fixture part of the 3-implant systems was almost identical . It is suggested that correctly performed implant installation may ensure proper conditions for both and hard tissue healing , and that the geometry of the titanium implant seems to be of limited importance OBJECTIVES the aim of this r and omized-controlled clinical trial was to compare the objective and subjective esthetic outcomes of two types of screwed-retained single-implant crowns . MATERIAL S AND METHODS participants were r and omly assigned to the test ( all-ceramic ) and control [ porcelain-fused-to-ceramic ( PFM ) ] groups and were seen under investigation at baseline ( B ) , crown insertion ( CI ) , 1-year follow-up ( 1Y ) , and 2-year follow-up ( 2Y ) . Objective parameters were assessed by an intra-oral digital photograph ( 1:1 ratio ) , a study cast , a st and ardized radiograph , periodontal/peri-implant measurements , and question naires were obtained for the subjective parameters . In addition , pink esthetic score ( PES ) and white esthetic score ( WES ) were calculated for both groups . For the subjective evaluation , a visual analogue scale ( VAS ) question naire was used to assess the level of patient satisfaction regarding the esthetic outcome . Then , nine expert clinicians visually inspected and assessed subjective evaluation at the professional level . Statistical analysis was used to compare between groups and investigational appointments . RESULTS twenty patients were included in the study , 10 allocated to the all-ceramic group and 10 to the PFM group . No statistically significant differences were observed for the objective measurements comparing the test and control groups . Minor chipping of the ceramic veneering material was observed in the two patients of control group . The mean difference for all groups comparing objective parameters revealed an increase of papilla height between time points . A slight recession ( 0.26 mm ) of the peri-implant mucosal margin at the implant site was observed between 1Y and 2Y . Mean values for PES and WES were 13.9 and 13.1 for the PFM group and for the all-ceramic group , respectively . These values were not statistically significant . Implant crown volume , outline , translucency , and characterization showed major discrepancies with the contra-lateral natural teeth . As for subjective parameters , VAS patients ' responses regarding their perceptions of the esthetic outcome showed no statistical differences between groups and clinicians ' accuracy scores were 50 % and 47 % for PFM and all-ceramic crowns , respectively . CONCLUSION PFM and all-ceramic single-implant restorations may be indistinguishable from each other regarding the objective /subjective assessment of esthetic integration . The material chosen for fabricating an implant crown per se does not ensure an optimal esthetic outcome if other esthetic parameters are not present AIM This 1-year prospect i ve RCT compared the outcome of minimally ( turned ) and moderately rough ( TiUnite ) implant surfaces . MATERIAL AND METHODS Two subgroups of patients were formed ; one group ( n = 10 ) where all teeth had been extracted due to severe periodontitis , another group ( n = 8) with teeth in the antagonistic jaw with a history of periodontitis and some remaining medium pockets ( 4 - 6 mm ) . Implants ( n = 85 , 43 turned & 42 TiUnite ) were installed r and omly in each patient . After 3 - 6 months of submerged healing , healing abutments were connected , followed by final abutments 2 weeks later , all with the same surface characteristics as the supporting implant . Peri-implant parameters and intra-oral radiographs were recorded up to 1 year after abutment connection . RESULTS Two turned implants failed in the partial edentulous group during the initial healing period ( CSR : 95 % ) and none of the TiUnite ( CSR : 100 % ) surface . No statistically significant differences in clinical parameters could be observed between both surfaces . The partial edentulous subgroup showed more bone loss compared to the full edentulous subgroup . CONCLUSION Moderately rough implants have a similar clinical outcome ( at 1 year of loading in periodontitis susceptible patients ) compared to minimally rough implants Patients ’ esthetic expectations are increasing , and the options of the prosthetic pathways are currently evolving . The objective of this r and omized multicenter clinical trial was to assess and compare the esthetic outcome and clinical performance of anterior maxillary all-ceramic implant crowns ( ICs ) based either on prefabricated zirconia abutments veneered with pressed ceramics or on CAD/CAM zirconia abutments veneered with h and buildup technique . The null hypothesis was that there is no statistically significant difference between the 2 groups . Forty implants were inserted in sites 14 to 24 ( FDI ) in 40 patients in 2 centers , the Universities of Bern and Geneva , Switzerl and . After final impression , 20 patients were r and omized into group A , restored with a 1-piece screw-retained single crown made of a prefabricated zirconia abutment with pressed ceramic as the veneering material using the cut-back technique , or group B using an individualized CAD/CAM zirconia abutment ( CARES abutment ; Institut Straumann AG ) with a h and buildup technique . At baseline , 6 mo , and 1 y clinical , esthetic and radiographic parameters were assessed . Group A exhibited 1 dropout patient and 1 failure , result ing in a survival rate of 94.7 % after 1 y , in comparison to 100 % for group B. No other complications occurred . Clinical parameters presented stable and healthy peri-implant soft tissues . Overall , no or only minimal crestal bone changes were observed with a mean DIB ( distance from the implant shoulder to the first bone-to-implant contact ) of −0.15 mm ( group A ) and 0.12 mm ( group B ) at 1 y. There were no significant differences at baseline , 6 mo , and 1 y for DIB values between the 2 groups . Pink esthetic score ( PES ) and white esthetic score ( WES ) values at all 3 examinations indicated stability over time for both groups and pleasing esthetic outcomes . Both implant-supported prosthetic pathways represent a valuable treatment option for the restoration of single ICs in the anterior maxilla ( Clinical Trials.gov NCT02905838 ) OBJECTIVES To ( i ) investigate the influence of different extensions of a laser microgrooved abutment zone on connective tissue attachment and ( ii ) assess the impact of a repeated abutment dis-/reconnection on soft- and hard-tissue healing . MATERIAL S AND METHODS Titanium implants were inserted epicrestally in the lower jaws of six dogs . Healing abutments with either partially ( LP ) or completely ( LC ) laser microgrooved margins or machined surface margins ( M ) were r and omly allocated either to a single (1 × )/repeated ( 2 × ) dis-/reconnection at 4 and 6 weeks ( test ) , respectively , or left undisturbed ( control ) . At 6 and 8 weeks , histomorphometrical ( e.g. most coronal level of bone in contact with the implant [ CBI ] , subepithelial connective tissue attachment [ STC ] ) and immunohistochemical ( Collagen Type-I [ CI ] ) parameters were assessed . RESULTS At control sites , LP/LC groups revealed lower mean CBL ( 8 weeks , 0.95 ± 0.51 vs. 0.54 ± 0.63 vs. 1.66 ± 1.26 mm ) , higher mean STC ( 8 weeks , 82.58 ± 24.32 % vs. 96.37 ± 5.12 % vs. 54.17 ± 8.09 % ) , but comparable CI antigen reactivity . A repeated abutment manipulation was associated with increased mean CBL ( 8 weeks , 1.53 ± 1.09 vs. 0.94 ± 0.17 vs. 1.06 ± 0.34 mm ) , decreased STC ( 8 weeks , 57.34 ± 43.06 % vs. 13.26 ± 19.04 % vs. 37.76 ± 37.08 % ) and CI values . CONCLUSIONS It was concluded that ( i ) LC > LP abutments enhanced subepithelial connective tissue attachment and preserved crestal bone levels , ( ii ) repeated abutment dis-/reconnection during the initial healing phase ( 4 - 6 weeks ) may be associated with increased soft- and hard-tissue changes and ( iii ) LP and LC should be considered using a one abutment , one time approach OBJECTIVES To test the survival rates , and the technical and biological complication rates of customized zirconia and titanium abutments 5 years after crown insertion . MATERIAL AND METHODS Twenty-two patients with 40 single implants in maxillary and m and ibular canine and posterior regions were included . The implant sites were r and omly assigned to zirconia abutments supporting all-ceramic crowns or titanium abutments supporting metal-ceramic crowns . Clinical examinations were performed at baseline , and at 6 , 12 , 36 and 60 months of follow-up . The abutments and reconstructions were examined for technical and /or biological complications . Probing pocket depth ( PPD ) , plaque control record ( PCR ) and Bleeding on Probing ( BOP ) were assessed at abutments ( test ) and analogous contralateral teeth ( control ) . Radiographs of the implants revealed the bone level ( BL ) on mesial ( mBL ) and distal sides ( dBL ) . Data were statistically analyzed with nonparametric mixed models provided by Brunner and Langer and STATA ( P < 0.05 ) . RESULTS Eighteen patients with 18 zirconia and 10 titanium abutments were available at a mean follow-up of 5.6 years ( range 4.5 - 6.3 years ) . No abutment fracture or loss of a reconstruction occurred . Hence , the survival rate was 100 % for both . Survival of implants supporting zirconia abutments was 88.9 % and 90 % for implants supporting titanium abutments . Chipping of the veneering ceramic occurred at three metal-ceramic crowns supported by titanium abutments . No significant differences were found at the zirconia and titanium abutments for PPD ( meanPPDZrO2 3.3 ± 0.6 mm , mPPDTi 3.6 ± 1.1 mm ) , PCR ( mPCRZrO2 0.1 ± 0.3 , mPCRTi 0.3 ± 0.2 ) and BOP ( mBOPZrO2 0.5 ± 0.3 , mBOPTi 0.6 ± 0.3 ) . Moreover , the BL was similar at implants supporting zirconia and titanium abutments ( mBLZrO2 1.8 ± 0.5 , dBLZrO2 2.0 ± 0.8 ; mBLTi 2.0 ± 0.8 , dBLTi 1.9 ± 0.8 ) . CONCLUSIONS There were no statistically or clinical ly relevant differences between the 5-year survival rates , and the technical and biological complication rates of zirconia and titanium abutments in posterior regions PURPOSE This is a 2-year report from an ongoing prospect i ve 5-year multicenter study . The aim of the study was to evaluate the short- and long-term clinical function of CerAdapt ceramic abutments supporting short-span fixed partial dentures ( FPD ) . MATERIAL S AND METHODS Initially , 105 Brånemark System implants were placed in a total of 32 patients at 3 different clinics . After initial healing 103 implants remained . For the support of 36 FPDs , 53 ceramic and 50 titanium abutments were connected , 19 on ceramic and Output:	The macroscopic design , the surface topography and the manipulation of the implant abutment did not have a significant influence on peri-implant inflammation . In contrast , the abutment material demonstrated increased BOP values over time for Ti when compared to Zi abutments
MS2704	*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 controversial evidence regarding whether foot orthoses or knee braces improve pain and function or correct malalignment in selected patients with osteoarthritis ( OA ) of the medial knee compartment . However , insoles are safe and less costly than knee bracing if they relieve pain or improve function . Questions / purpose sWe therefore asked whether laterally wedged insoles or valgus braces would reduce pain , enhance functional scores , and correct varus malalignment comparable to knee braces . Patients and Methods We prospect ively enrolled 91 patients with symptomatic medial compartmental knee OA and r and omized to treatment with either a 10-mm laterally wedged insole ( index group , n = 45 ) or a valgus brace ( control group , n = 46 ) . All patients were assessed at 6 months . The primary outcome measure was pain severity as measured on a visual analog scale . Secondary outcome measures were knee function score using WOMAC and correction of varus alignment on AP whole-leg radiographs taken with the patient in the st and ing position . Additionally , we compared the percentage of responders according to the OMERACT-OARSI criteria for both groups . Results We observed no differences in pain or WOMAC scores between the two groups . Neither device achieved correction of knee varus malalignment in the frontal plane . According to the OMERACT-OARSI criteria , 17 % of our patients responded to the allocated intervention . Patients in the insole group complied better with their intervention . Although subgroup analysis results should be translated into practice cautiously , we observed a slightly higher percentage of responders for the insole compared with bracing for patients with mild medial OA . Conclusions Our data suggest a laterally wedged insole may be an alternative to valgus bracing for noninvasively treating symptoms of medial knee OA.Level of Evidence Level I , therapeutic study . See the Guidelines for Authors for a complete description of level of evidence We examined if a subject-specific amount of lateral wedge added to a foot orthosis could alter knee mechanics to potentially reduce the progression of knee osteoarthritis in patients with medial knee osteoarthritis . Twenty individuals with medial knee osteoarthritis ( > /=2 Kellgren Lawrence grade ) were prescribed a custom laterally wedged foot orthotic device . The prescribed wedge amount was the minimal wedge amount that provided the maximum amount of pain reduction during a lateral step-down test . Following an accommodation period , all subjects returned to the laboratory for a gait analysis . Knee mechanics were collected as the subjects walked at an intentional walking speed . Walking in the laterally wedged orthotic device significantly reduced the peak adduction moment during early stance ( p < 0.01 ) compared to the nonwedged device . Similarly , the wedged orthotic device significantly reduced the knee adduction excursion from heel strike to peak adduction ( p < 0.01 ) compared to the nonwedged device . No differences in the peak adduction moment during propulsion or peak adduction during stance were observed between the orthotic conditions . A subject-specific laterally wedged orthotic device was able to reduce the peak knee adduction moment during early stance , which is thought to be associated with the progression of knee osteoarthritis . Previous studies on this device have reported issues associated with foot discomfort when using wedge amounts > 7 degrees ; however , no such issues were reported in this study . Therefore , providing a custom laterally wedged orthotic device may potentially increase compliance while still potentially reducing disease progression OBJECTIVE To compare the clinical effects of laterally wedged insoles and neutrally wedged insoles ( used as control ) in patients with medial femoro-tibial knee osteoarthritis ( OA ) . DESIGN 6-month prospect i ve r and omized controlled study . PATIENTS out patients with painful medial femoro-tibial knee OA . OUTCOME MEASURES patient 's overall assessment of disease activity ( 5 grade scale ) , WOMAC index subscales and concomitant treatments . STATISTICAL ANALYSIS Performed as an intention-to-treat analysis . Main criterion : improvement in the patient 's assessment of activity ( defined as a reduction of 1 grade or more at month 6 compared to baseline , and no intraarticular injection or lavage during the study ) . Secondary criteria for assessment : ( a ) improvement in the patient 's assessment of activity at months 1 and 3 compared to baseline , ( b ) improvement in the WOMAC subscales at months 1 , 3 and 6 , compared to baseline ( defined as an improvement of at least 30 % , and no intraarticular injection or lavage during the study ) and ( c ) concomitant therapies ( analgesics and NSAIDs ) . RESULTS The baseline characteristics of the 156 recruited patients ( 41 males , 115 females , mean age 64.8 years ) were not different in the two treatment groups . At months 1 , 3 and 6 the percentages of patients with improvement in assessment of disease activity , in WOMAC pain , joint stiffness , and physical functioning subscales were similar in the two groups . The number of days with NSAIDs intake during the previous 3 months was decreased at month 6 compared with baseline in the group furnished with laterally wedged insoles ( 14.1 days+/-28 vs 9.9 days+/-27 , P=0.04 , Wilcoxon paired test ) , while it remained unchanged in the other group ( 15.5 days+/-24 vs 15+/-28 , P=0.56 ) . Compliance and tolerance were satisfactory . Compliance was different between the two groups at month 6 , with a greater frequency of patients who wore insoles permanently in the laterally wedged insole group than in the other group ( 87.8 % vs 74.3%;P=0.032 ) . CONCLUSION This study failed to demonstrate a relevant short-term symptomatic effect of laterally-wedged insoles in medial femoro-tibial OA . However , the decrease in NSAIDs consumption together with better compliance in the treated group are in favor of a beneficial effect of laterally-wedged insoles in medial femoro-tibial OA Objective This study aim ed to determine whether the effect of laterally wedged insoles on the adduction moment in knee osteoarthritis ( OA ) declined after one month of wear , and whether higher reported use of insoles was associated with a reduced effect on the adduction moment at one month . Methods Twenty people with medial compartment OA underwent gait analysis in their own shoes wearing i ) no insoles and ; ii ) insoles wedged laterally 5 ° in r and om order . Testing occurred at baseline and after one month of use of the insoles . Participants recorded daily use of insoles in a log-book . Outcomes were the first and second peak external knee adduction moment and the adduction angular impulse , compared across conditions and time with repeated measures general linear models . Correlations were obtained between total insole use and change in gait parameters with used insoles at one month , and change scores were compared between high and low users of insoles using general linear models . Results There was a significant main effect for condition , whereby insoles significantly reduced the adduction moment ( all p < 0.001 ) . However there was no significant main effect for time , nor was an interaction effect evident . No significant associations were observed between total insole use and change in gait parameters with used insoles at one month , nor was there a difference in effectiveness of insoles between high and low users of the insoles at this time . Conclusion Effects of laterally wedged insoles on the adduction moment do not appear to decline after one month of continuous use , suggesting that significant wedge degradation does not occur over the short-term Objective To assess the effect of lateral wedge insoles compared with flat control insoles on improving symptoms and slowing structural disease progression in medial knee osteoarthritis . Design R and omised controlled trial . Setting Community in Melbourne , Australia . Participants 200 people aged 50 or more with clinical and radiographic diagnosis of mild to moderately severe medial knee osteoarthritis . Interventions Full length 5 degree lateral wedged insoles or flat control insoles worn inside the shoes daily for 12 months . Main outcome measures Primary symptomatic outcome was change in overall knee pain ( past week ) measured on an 11 point numerical rating scale . Primary structural outcome was change in volume of medial tibial cartilage from magnetic resonance imaging scans . Secondary clinical outcomes included changes in measures of pain , function , stiffness , and health related quality of life . Secondary structural outcomes included progression of medial cartilage defects and bone marrow lesions . Results Between group differences did not differ significantly for the primary outcomes of change in overall pain ( −0.3 points , 95 % confidence intervals −1.0 to 0.3 ) and change in medial tibial cartilage volume ( −0.4 mm3 , 95 % confidence interval −15.4 to 14.6 ) , and confidence intervals did not include minimal clinical ly important differences . None of the changes in secondary outcomes showed differences between groups . Conclusion Lateral wedge insoles worn for 12 months provided no symptomatic or structural benefits compared with flat control insoles . Trial registration Australian New Zeal and Clinical Trials Registry ACTR12605000503628 and Clinical Trials.gov NCT00415259 The purpose of the study was to examine the clinical efficacy of individually prescribed laterally wedged orthoses and walking shoes in the treatment of medial knee osteoarthritis using a prospect i ve , single-blind , block-r and omized controlled design . Sixty-six subjects ( 29 males , 37 females , mean age 62.4 years , mean BMI 33.0 kg/m(2 ) ) were block-r and omized to a lateral wedge ( treatment ) or neutral ( control ) orthotic group . Both groups were issued a st and ardized walking shoe for use with the orthoses . Primary outcome measures included the pain , stiffness , and functional limitations subscales of the Western Ontario and McMaster Universities index . Secondary outcome measures included the 6-minute walk distance and pain change , and stair negotiation time and pain change . A significant interaction ( p=0.039 ) favoring the treatment group was observed for pain change during the 6-minute walk . The treatment group demonstrated significant improvements at both 1 month ( p<0.001 ) and 1 year ( p<0.001 ) compared to baseline . The control group only demonstrated significant improvements at 1 year ( p=0.017 ) . No other interactions were observed . Both groups were improved at each follow-up in the WOMAC subscales for pain ( p<0.001 ) , stiffness ( p<0.001 ) , and physical function ( p<0.001 ) . Both groups also improved in 6-minute walk test distance ( p<0.001 ) , stair negotiation test time ( p=0.004 ) , and stair negotiation test pain change ( p<0.001 ) . The results suggest that both neutral and laterally wedged orthoses may be beneficial in the management of medial knee osteoarthritis when used with walking shoes . However , the addition of lateral wedging was associated with early improvements in 6-minute walk test pain change not seen in the control group OBJECTIVE To compare the clinical effects of laterally wedged insoles and neutrally wedged insoles ( used as control ) in patients with medial femoro-tibial knee osteoarthritis . METHODS STUDY DESIGN 24-month prospect i ve r and omized controlled study . PATIENTS Out patients with painful medial femoro-tibial knee osteoarthritis . OUTCOME MEASURES Patient 's overall assessment of disease activity ( 5 grade scale ) , WOMAC index subscales and concomitant treatments . STATISTICAL ANALYSIS Performed as an intention-to-treat analysis , with the last observation carried forward ( LOCF ) . Main symptomatic criterion : Improvement in the patient 's assessment of activity ( defined as a reduction of one grade or more at the end of the study as compared to baseline , and no intra-articular injection or lavage during the 6 months previous to the last visit ) . Secondary criteria for assessment : ( a ) Changes in the WOMAC subscales at month 24 , and ( b ) concomitant therapies ( analgesics , NSAIDs and intra-articular injections or lavages ) . Structural criterion : Joint space width ( JSW ) at the narrowest point . Non-compliance was defined as intermittent or lack of insole fitting at two consecutive visits . Compliance within groups was compared by using a life table analysis technique ( Log-Rank ) . RESULTS The baseline characteristics of the 156 recruited patients ( 41 males , 115 females , mean age 64.8 years ) were not different in the 2 treatment groups . At year 2 , there was no statistically significant difference between the 2 groups concerning the percentages of patients with improvement in both global assessment of disease activity and in WOMAC subscales ( pain , stiffness , function ) . The number of days with NSAIDs intake was lower in the group with laterally wedged insoles than in the neutrally wedged group ( 71+/-173 days vs. 127+/-193 days , P=0.003 , Mann-Whitney test ) . The mean joint space narrowing rate did not differ between the two groups : 0.21+/-0.59 mm/year in the laterally wedged group vs 0.12+/-0.32 mm/year in the neutrally wedged group . Compliance and tolerance were satisfactory . Compliance was different between the 2 groups at month 24 , with a greater frequency of patients who wore insoles permanently in the laterally wedged insole group than in the other group ( 85.8 % vs 71.9 % , P=0.023 ) . CONCLUSION This study failed to demonstrate a relevant symptomatic and /or structural effect of Output:	To conclude , there is limited evidence to support the prescription of LWI to people with medial compartment osteoarthritis to reduce pain and increase function . However , there remains a paucity of evidence to determine whether LWI outcomes differ in subgroups of the patients , such as severe compared to mild osteoarthritis , obese patients , or whether the angle of LWI is of clinical importance
MS2705	*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 Few trials have evaluated the effects of antibiotics on symptoms of the irritable bowel syndrome ( IBS ) . Contribution In this double-blind trial , 87 patients with IBS were r and omly assigned to either rifaximin ( 400 mg 3 times daily ) or placebo for 10 days . Over a 10-week follow-up period , the rifaximin recipients reported global improvements in overall symptoms and less bloating more frequently than the placebo recipients . No major differences in abdominal pain , diarrhea , or constipation were observed between the groups . Caution s The duration of therapy and follow-up was short . Implication s Rifaximin may improve some symptoms in some patients with IBS . The Editors The irritable bowel syndrome ( IBS ) is one of the most common chronic medical conditions ( 16 ) , yet its cause is unknown . Among other contributors , alterations in gut flora have been identified as potentially important . Results of recent studies indicate that up to 84 % of patients with IBS have an abnormal lactulose breath test result , suggesting small-intestinal bacterial overgrowth ( 7 , 8) . On the basis of this concept , the antibiotic neomycin can statistically significantly improve the symptoms of IBS ( 7 , 8) . In addition , the effect of neomycin correlates with the elimination of bacterial overgrowth , as indicated by the normalization of the lactulose breath test result ( 7 , 8) . Although neomycin seems to improve symptoms , it effectively eliminates bacterial overgrowth in only about 25 % of patients with IBS ( 8) . Furthermore , side effects limit the use of neomycin . Low efficacy also applies to other antibiotics ( for example , doxycycline and amoxicillinclavulanate ) that have been previously investigated for treating bacterial overgrowth ( 9 ) . An ideal antibiotic for IBS is , arguably , one with negligible systemic absorption , minimal side effects , and high efficacy for bacterial overgrowth . Rifaximin is a gut-selective antibiotic with negligible systemic absorption ( 0.4 % ) and broad-spectrum activity in vitro against gram-positive and gram-negative aerobes and anaerobes ( 10 ) . On the basis of this broad spectrum , eradication rates with rifaximin in bacterial overgrowth are as high as 70 % ( 11 ) . Furthermore , rifaximin has a similar tolerability profile to that of placebo and has known activity against Clostridium difficile ( 12 ) . These properties make it a good c and i date for treating a condition that is as common as IBS . Our study aim ed to determine whether the nonabsorbed antibiotic rifaximin is more effective than placebo in reducing symptoms in adults with IBS . Methods Setting and Participants Our study was conducted at the Cedars-Sinai Medical Center , Los Angeles , California , and the University of Chicago , Chicago , Illinois . We recruited patients with IBS through advertising in local media ( radio and news publications ) . We did not recruit patients from the IBS clinics of the Cedars-Sinai Gastrointestinal Motility Program to avoid enrollment of tertiary care patients . The institutional review board of both centers approved the study , and all patients provided written informed consent . Patients between 18 and 65 years of age who met Rome I criteria ( 13 ) were eligible . Exclusion criteria were the presence of underlying conditions that are known to predispose to bacterial overgrowth , including diabetes ; narcotic use ; previous bowel resection ; inflammatory bowel disease ; cirrhosis ; known bowel adhesions ; or any known chronic gastroenterological disease , such as celiac disease . We excluded patients who were taking tegaserod and antidepressants unless these treatments were discontinued before study entry . We also excluded participants who reported taking an oral antibiotic within the previous 3 months . After participant inclusion and exclusion , we recruited 84 participants from the Cedars-Sinai Medical Center and 3 participants from the University of Chicago . We followed participants in special research clinics at both centers . R and omization and Interventions Eligible patients completed a 7-day stool diary that was based on the Bristol stool form scale ( 14 ) . Patients returned to the clinic after a 12-hour fast and completed a symptom question naire about the preceding 7 days of symptoms . We then r and omly assigned patients to double-blind treatment with 400 mg of rifaximin 3 times daily for 10 days or a matching placebo . We chose this dosage on the basis of a previous study that demonstrated the efficacy of rifaximin in bacterial overgrowth ( 11 ) . The r and omization of rifaximin versus placebo was conducted outside of Cedars-Sinai Medical Center in a 1:1 ratio into blocks of 4 patients . The allocation sequence was determined and coded at Salix Pharmaceuticals , Morrisville , North Carolina . Since this was an investigator-initiated study , the rifaximin and placebo were distributed to the Cedars-Sinai Medical Center , and nonstratified medicine and placebo were sent to the University of Chicago in groups of 4 as enrollment progressed . The medicine and placebo were prepackaged to conceal content at all times . Research personnel who were involved in product distribution were also blinded to package content . Assessment s and Follow-up After completing the 10-day course of study medication , patients immediately began another stool diary for 7 days then returned to complete a follow-up question naire and to return their pill container for a pill count to determine adherence . Patients then entered the follow-up phase , during which they completed a weekly self-administered symptom question naire at home that documented their symptoms for an additional 9 weeks ( for a total of 10 weeks of post-treatment follow-up ) . During this time , we asked participants to fax their responses to the research office . When a fax was not received on the appropriate day , research assistants called patients to ensure adherence . During this phase of study , no physician interaction occurred . During the last week of follow-up , patients completed a daily stool diary . At the end of the follow-up period , patients returned to the clinic for a final visit , which included another symptom question naire . For the initial symptom question naire , patients were asked to indicate the severity of each of 9 symptoms ( abdominal pain , diarrhea , constipation , bloating , urgency , incomplete evacuation , mucus , sense of incomplete evacuation , and gas ) on a visual analogue scale ( VAS ) ranging from 0 mm to 100 mm , with 100 mm being extreme . We used all 9 symptoms to verify IBS criteria in patients , but we assigned only diarrhea , constipation , abdominal pain , and bloating a priori as treatment end points . We asked patients to rate the severity of their symptoms on the VAS again 7 days after the completion of rifaximin treatment or placebo . Furthermore , we asked patients to provide a percentage of global improvement in their overall IBS symptoms from 0 % to 100 % . We chose global improvement since the Rome Consensus Group considers it to be the preferred end point measure in IBS treatment studies ( 15 ) . Patients then rated the severity of their symptoms on the VAS and rated global improvement again each week for 8 weeks of follow-up and at the final visit to provide a total of 10 weeks of follow-up data . Table 1 depicts the number of patients with outcomes at various time points during the study . Table 1 . Study Recruitment and Enrollment Summary At the first follow-up visit , physicians evaluated adverse events by asking patients , in an open-ended manner , whether they had experienced adverse events while receiving therapy and to elaborate on any that occurred . Although breath testing and breath methane level determinations were performed , we do not report them in our paper . Statistical Analysis We determined the number of patients for the study on the basis of the neomycin effect in a recent double-blind study for IBS on global improvement ( 8) . To detect a difference of 35 % ( SD , 50 % ) with a power of 90 % , we needed to assign 44 participants per group . Assuming a dropout rate of 10 % , we calculated that approximately 96 patients would need to be recruited . The primary end point was global improvement in IBS symptoms during follow-up . As seen in Figure 1 , data were not available for all 10 weeks of follow-up . Figure 1 . Study flow chart . We assessed the primary end point ( percentage of global improvement ) across the 10 weeks of follow-up by using an approach analogous to a repeated measures analysis of variance . Specifically , we used a mixed model with visit week ( at 10 levels ) , treatment group ( rifaximin or placebo ) , and group-by-week interaction as the fixed factors and patient as the r and om factor . The interaction and group factors were the main factors of interest in the analyses . We estimated mixed models by using the restricted maximum likelihood method . Because the global improvement percentage varied widely across week for most individuals , we considered week to be a categorical variable in the mixed model . Within-patient correlation across time was addressed by an autoregressive ( first-order ) model for the covariance structure . Missing data were mostly intermittent , and we assumed them to be missing at r and om . The normality assumption was rarely satisfied in either group at any week . However , at least 34 observations were recorded per group per week and the sample sizes were well-balanced , so we used the mixed-model analysis . We analyzed models with a single covariate ( baseline diarrhea , constipation , abdominal pain , or bloating severity score ) . The covariate models did not improve the fit nor did they change the substantive results . Hence , we presented the simpler ( no covariate ) model results . We used a similar mixed-model approach to assess the secondary end points of abdominal pain , bloating , diarrhea , and constipation . Within-patient correlation was modeled by an autoregressive covariance structure . The normality assumption was rarely satisfied for the diarrhea outcome , with a similar floor effect for the primary outcome Abstract The relationship between methanogenic flora and hydrogen ( H2 ) production is considered to be a possible confounding factor in the interpretation of hydrogen breath tests ( H2BT ) . Therefore , the present study was conducted prospect ively and included 154 IBS patients ( fulfilling Rome II criteria ) and 286 age- and -sex-matched apparently healthy controls . Each subject underwent H2BT after overnight fasting using 25 g lactose . Methane and H2 were measured using an SC Microlyser from Quintron , USA , at baseline and every 30 min for a total of 4 h. Subjects with fasting methane concentration < 10 ppm were labeled as low methane producers ( LMP ) and > 10 ppm as predominant methane producers ( PMP ) . A rise > 20 ppm over base line in hydrogen concentration was taken as + ve hydrogen breath test . IBS and control groups included 66.78 % and 67.53 % males , respectively . Mean age in the two groups were 48.52 ± 30.54 years ( range 15–68 years ) and 45.67 ± 30.54 years ( range 15–78 years ) , respectively . Hydrogen breath test was + ve in 77/154 ( 50 % ) IBS patients and in 142/286 ( 49.65 % ) in controls ( P > 0.05 ) . It was also observed that the hydrogen breath test was −ve due to PMP in 5/77 ( 6.49 % ) of IBS patients and in 29/154 ( 20.14 % ) in controls . PMP affected lactose hydrogen breath tests in 6.49–20.14 % subjects . This effect is more apparent in apparently healthy subjects as compared to patients with IBS PURPOSE Small intestinal bacterial overgrowth ( SIBO ) may coexist with irritable bowel syndrome ( IBS ) and eradication therapy has been reported as effective in reducing IBS symptoms . Aims of this study were to : ( 1 ) Assess the clinical profiles of IBS patients , who underwent breath testing with a glucose substrate -- glucose breath test ( GBT ) ; ( 2 ) Evaluate hydrogen and methane parameters in various IBS groups ; ( 3 ) Assess the role of inhibition of gastric acid in contributing to SIBO ; ( 4 ) Investigate efficacy and safety of non-absorbable antibiotic rifamixin for eradication and symptom relief . METHODS 204 IBS patients met the ROME II criteria for IBS ( 170F & 34 M ; mean age 46.4 ; range 18 - 88 ) and underwent GBT . 8 of these patients with positive GBT were treated with rifaximin 200 mg , 4 times a day for 1 month and symptom assessment s and GBT were repeated . RESULTS 93 ( 46 % ) had a positive GBT . 68 ( 73 % ) of these 93 IBS-diarrhea dominant ( IBS-D ) , 12 ( 13 % ) were constipation dominant ( IBS-C ) and 13 ( 14 % ) IBS with alternating bowel pattern . 48 % of SIBO positive patients were receiving PPI therapy compared to 40 % of IBS patients with negative GBT . 61 ( 66 % ) produced only hydrogen , 27 ( 29 % ) methane only , and 5 ( 5 % ) both-hydrogen and methane . There were more methane producers in IBS-C then IBS-D group ( 58 % vs 28 % ) while IBS-D had more hydrogen formers ( 71 % vs 42 % ) . 8 patients with SIBO ( 7F & IM ; mean age 55 , range 31 - 85 ) received rifamixin 800 mg/day . Repeat GBT was normal in 6 ( 75 % ) Output:	Conclusions We demonstrate that methane present on breath testing is significantly associated with constipation in both IBS and functional constipation . These results suggest there may be merit in using breath testing in constipation . Moreover , methane may be used to identify c and i date s for antibiotic treatment of constipation
MS2706	*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 evaluate the long-term outcome of In-Ceram Alumina fixed partial dentures ( FPD ) performed in a general dental practice from 1992 to 1996 . MATERIAL S AND METHODS The study was conducted as a retrospective assessment of up to 9 years of patient records and a clinical follow-up examination of patients treated with In-Ceram Alumina FPDs . In 37 patients , 42 FPDs had been inserted during the selected period . After r and omized selection , 16 patients with 18 FPDs were examined clinical ly . The most common restorations comprised two and three units . Cantilever extensions were present on 64 % of the FPDs . Sixty-two percent of the FPDs extended into the posterior region . RESULTS The mean time in function for the 42 FPDs was 76 months ( range 2 to 110 months ) , with 86 % being followed for > 5 years . No adverse effects to either periodontal or pulpal tissues were recorded . The technical quality was very good , and patient satisfaction very high . Five FPDs fractured during the observation period , result ing in a total failure rate of 12 % . Two of these FPDs fractured as a consequence of external trauma . Excluding these , the total survival rate during the observation period was 93 % . Cumulative survival rate according to life table analysis was 93 % after 5 years and 83 % after 10 years . CONCLUSION The results suggest that the In-Ceram Alumina short-span FPD is a viable prosthetic alternative PURPOSE The aim of this prospect i ve study was to evaluate the clinical efficacy and long-term survival rate of three-unit fixed partial dentures ( FPDs ) made from lithium disilicate-based core ceramic . MATERIAL S AND METHODS Twenty-one three-unit FPDs were placed in 19 patients to replace single lost teeth in the esthetic area , following a study protocol that took clinical , esthetic , and radiologic aspects into consideration . Each case was review ed at 1 week following placement , at 6 months , and then annually for 10 years . Statistical analysis was performed using Kaplan-Meier survival analysis . RESULTS Out of the 19 patients , 14.3 % presented reversible postoperative sensitivity . Recession was observed in 24 % of dental posts , and 7.1 % presented marginal discoloration . Treatment did not increase either Bleeding or Plaque Index scores at prepared teeth ; secondary caries did not appear either . The restorations ' survival rate at the 10-year follow-up was 71.4 % ; six FPDs had fractured and one debonded . CONCLUSIONS Fracture failure rate was 28.6 % after 10 years ; a high percentage corresponded to connector fractures and occurred during the first 5 years . Lithium disilicate glass-ceramic FPDs present a higher risk of fracture than st and ard therapies ( metal-ceramic ) or other more recently developed ceramic material s. The prognosis for survival improves for Class I occlusion and nonparafunctional patients STATEMENT OF PROBLEM Although the favorable mechanical properties of zirconium oxide-based ceramics have increased the acceptance of fixed dental prostheses for use in the posterior regions of the mouth in recent years , there are few clinical studies documenting the longevity of these restorations . Furthermore , certain complications must be resolved before the material is used more extensively . PURPOSE The purpose of this r and omized prospect i ve study was to evaluate the clinical performance of zirconia ( Lava ) 3-unit posterior fixed dental prostheses . MATERIAL AND METHODS Twenty 3-unit fixed dental prostheses were placed in 17 participants to replace a second premolar or a first molar . Eleven were placed in the maxilla and 9 in the m and ible . All abutment teeth were prepared with a chamfer finish line of 0.8 to 1 mm , and frameworks were prepared with the Lava system . Restorations were cemented with a resin cement . Two calibrated examiners independently evaluated the fixed dental prostheses 1 week ( baseline ) and 1 , 2 , and 3 years after placement with the California Dental Association quality evaluation system . The periodontal parameters : the gingival index , plaque index , margin index , and the probing depths of abutment teeth and contralateral teeth were assessed . Data were analyzed by using descriptive statistics and the Wilcoxon signed-rank test ( α=.05 ) . RESULTS All fixed dental prostheses were rated satisfactory after 3 years , and no fracture of the framework was observed during the observation period . One fixed dental prostheses was lost because of a biological complication at the 3-year examination , and a small degree of chipping of the veneering ceramic was observed in 2 participants . No significant differences among the periodontal parameters of the test and control teeth were observed except for the margin index . CONCLUSIONS The results of a 3-year evaluation suggest that posterior zirconia 3-unit fixed dental prostheses are a reliable treatment This study aim ed to evaluate three- and four-unit posterior fixed partial dentures ( FPDs ) with zirconia frameworks after 5 years of function . Of the initial 30 subjects , 25 patients with 25 FPDs were examined after a mean follow-up period of 62.1 months . Five patients were not available for recall visits . Two FPDs failed before the 60-month evaluation because of framework fracture or delamination of the veneering ceramic after endodontic treatment . The 5-year survival rate was 92 % . Based on these results , it can be suggested that zirconia frameworks have sufficient mechanical requirements for use in the stress-bearing posterior region . Major fracture of the ceramic veneer could be related to inadequate framework design or bruxism The aim of this r and omized controlled trial was to evaluate the clinical performance of lithium disilicate fixed partial dentures ( FPDs ) . Eighteen patients received lithium disilicate FPDs ( study group ) , and 19 patients received porcelain-fused-to-metal FPDs ( control ) . After 6 years , the survival probabilities were found to be 63 % in the study group and 95 % in the control group ( log-rank test , P = .028 ) . The data suggest that strict conditions should be considered before the use of lithium disilicate glass-ceramic for FPDs OBJECTIVES The purpose of this prospect i ve study was to evaluate the clinical outcome of crown-retained fixed dental prostheses ( FDPs ) made from a lithium-disilicate glass-ceramic ( IPS e.max Press , Ivoclar-Vivadent ) . METHODS Thirty-six three-unit FDPs were placed in 28 patients . The FDPs replaced teeth in the anterior ( 16 % ) and posterior ( 84 % ) regions . All teeth were prepared following a st and ardized protocol . The size of the proximal connector of the FDPs was 12 mm2 ( anterior ) or 16 mm2 ( posterior ) . FDPs were cemented either with glass-ionomer cement ( n=19 ) or composite resin ( n=17 ) . The following parameters were evaluated at baseline , 6 months after cementation and then annually ( at abutment and contralateral teeth ) : probing pocket depth , plaque index , bleeding on probing , and tooth vitality . RESULTS Three FDPs were defined as drop-out . The mean observation period of the remaining 33 FDPs was 86 months ( range : 67 - 98 months ) : two FDPs in two patients had to be replaced ( 6 % ) because of fractures . The 8-year survival rate according to Kaplan-Meier was 93 % . In addition , chipping of the veneering material was found in two FDPs ( 6 % ) . Two abutments ( 3 % ) of two restorations had to be treated endodontically ; and two FDPs ( 6 % ) lost retention and had to be recemented . These complications did not affect the function of the involved restorations clinical ly . There were no significant differences between the periodontal parameters of the test and control teeth . SIGNIFICANCE Short-span crown-retained three-unit FDPs made from lithium-disilicate glass-ceramic can be used clinical ly irrespective of an adhesive or conventional cementation PURPOSE The aim of this prospect i ve clinical cohort study was to determine the success rate of 3- to 5-unit zirconia frameworks for posterior fixed partial dentures ( FPDs ) after 5 years of clinical observation . MATERIAL S AND METHODS Forty-five patients who needed at least 1 FPD to replace 1 to 3 posterior teeth were included in the study . Fifty-seven 3- to 5-unit FPDs with zirconia frameworks were cemented with 1 of 2 resin cements ( Variolink or Panavia TC ) . The following parameters were evaluated at baseline , after 6 months , and 1 to 5 years after cementation at test ( abutments ) and control ( contralateral ) teeth : probing pocket depth , probing attachment level , Plaque Index , bleeding on probing , and tooth vitality . Intraoral radiographs of the FPDs were taken . Statistical analysis was performed using descriptive statistics , Kaplan-Meier survival analysis , and the McNemar test . RESULTS Twenty-seven patients with 33 zirconia FPDs were examined after a mean observation period of 53.4 + /- 13 months . Eleven patients with 17 FPDs were lost to follow-up . After the 3-year recall visit , 7 FPDs in 7 patients were replaced because they were not clinical ly acceptable due to biologic or technical complications . After 5 years of clinical observation , 12 FPDs in 12 patients had to be replaced . One 5-unit FPD fractured as a result of trauma after 38 months . The success rate of the zirconia frameworks was 97.8 % ; however , the survival rate was 73.9 % due to other complications . Secondary caries was found in 21.7 % of the FPDs , and chipping of the veneering ceramic in 15.2 % . There were no significant differences between the periodontal parameters of the test and control teeth . CONCLUSIONS Zirconia offers sufficient stability as a framework material for 3- and 4-unit posterior FPDs . The fit of the frameworks and veneering ceramics , however , should be improved OBJECTIVE The aim of this prospect i ve clinical study was to evaluate the survival rates of IPS Empress 2 ( Ivoclar Vivadent ) all-ceramic crowns and fixed partial dentures ( FPDs ) after an observation period of up to 5 years . METHOD AND MATERIAL S Forty-three patients ( 19 women and 24 men ) were included in this study . The patients were treated with a total of 58 adhesive bonded IPS Empress 2 restorations . A total of 27 single crowns were placed on molars and premolars , and 31 three-unit FPDs were placed in the anterior and premolar regions . Clinical follow-up examinations took place at 6 , 12 , 24 , 36 , 48 , and 60 months after insertion . Statistical analysis of the data was calculated using the Kaplan-Meier method . RESULTS Results of the 50-month analysis ( interquartile range , 33 to 61 months ) showed that the survival rate was 100 % for crowns and 70 % for FPDs . Six failures that occurred exclusively in the three-unit FPDs were observed . Framework fractures were recorded in three FPD units where the connector dimensions did not meet the manufacturer specifications . Only one FPD exhibited an irreparable partial veneer fracture , and 2 FPDs showed evidence of biologic failures . The accuracy of fit and esthetic parameters were clinical ly satisfactory for crowns and FPDs . CONCLUSION The results of this 5-year clinical evaluation suggest that IPS Empress 2 ceramic is an appropriate material for the fabrication of single crowns . Because of the reduced survival rates , strict conditions should be considered before the use of IPS Empress 2 material for the fabrication of three-unit FPDs PURPOSE The aim of this prospect i ve study was to evaluate the clinical performance of zirconia-based posterior four-unit fixed dental prostheses ( FDPs ) after 4 years of clinical observation . MATERIAL S AND METHODS Between 2006 and 2010 , 10 patients ( 5 women , 5 men ; mean age : 52.8 years ) received 17 posterior four-unit FDPs . Two calibrated examiners evaluated the FDPs independently 1 week ( baseline ) , 6 months , and 1 , 2 , 3 , and 4 years after placement using California Dental Association ( CDA ) criteria . Periodontal status was assessed on both the abutment and contralateral control teeth using Plaque Index , Gingival Index , probing attachment level , and Margin Index parameters . Statistical analysis was performed using descriptive statistics and the Wilcoxon signed-rank test . RESULTS Three restorations were lost because of fractures at their distal connectors after a mean clinical service of 25.3 months , and one abutment tooth was extracted because of vertical root fracture 23 months after cementation . Three FDPs presented chipping of a moderate size 1 week before framework fracture , and minor chipping was observed in 2 other FDPs 1 week and 36 months after cementation . After 4 years of clinical service , the cumulative survival rate of the posterior four-unit FDPs was 76.5 % . No caries lesions were detected on the abutment teeth . The remaining restorations were judged to be satisfactory according to the CDA criteria . Periodontal parameters Output:	A significantly higher incidence of caries in abutment teeth was observed for densely sintered zirconia FDPs compared to metal-ceramic FDPs . Survival rates of all types of all-ceramic FDPs were lower than those reported for metal-ceramic FDPs . The incidence of framework fractures was significantly higher for reinforced glass ceramic FDPs and infiltrated glass ceramic FDPs , and the incidence for ceramic fractures and loss of retention was significantly higher for densely sintered zirconia FDPs compared to metal-ceramic FDPs
MS2707	*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 r and omized , open clinical trial was performed to compare azithromycin and amoxycillin/clavulanate potassium in children with acute otitis media with effusion . Patients were allocated to therapy with azithromycin ( 10 mg/kg once daily for 3 days ) or amoxycillin/clavulanate potassium ( 40 mg/kg/day divided into three equal doses for 10 days ) . Clinical examination and tympanometric evaluation were performed at baseline , and at day 3 to 5 , day 10 to 14 , day 28 to 30 and day 55 to 60 after the initiation of therapy . Tympanocentesis fluid cultures were collected at enrolment , and urine and blood sample s were obtained at baseline and at day 10 to 11 . Of 100 patients enrolled , 92 were considered evaluable . Middle ear cultures were positive in 53.2 % of the patients ; the most common pathogens were Streptococcus pneumoniae ( 33 % ) and Haemophilus influenzae ( 33 % ) . The response was satisfactory in 47 ( 100 % ) patients treated with azithromycin and 42 ( 95.4 % ) patients receiving A/C. Rates of persistence of middle ear effusion were comparable . Nausea and loose stools were more common in children treated with amoxycillin/clavulanate potassium ( P < or = 0.02 ) . Based on the comparable efficacy noted in this study , the lower incidence of side-effects and the convenience of a shorter duration of treatment , azithromycin represents an attractive therapeutic alternative to amoxycillin/clavulanate potassium and should be further evaluated in larger-scale clinical trials including patients with penicillin-resistant organisms A double-blind controlled trial of cefroxadine ( CXD ) 250 mg t.i.d . was undertaken to objective ly evaluate its safety and effectiveness in the treatment of acute suppurative otitis media and acute exacerbation of chronic suppurative otitis media , using cephalexin ( CEX ) 250 mg q.i.d . as a control drug , and the following results were obtained . In the treatment of acute suppurative otitis media , the 2 drugs produced almost equal outcomes , showing no significant difference in assessment s of both overall effects and usefulness . In the treatment of acute exacerbation of chronic suppurative otitis media , the 2 drugs exhibited no significant difference as well in overall effects by Wilcoxon 's two- sample test . However , the CEX group had significantly more nonresponsive patients , i.e. 35.5 % as compared with 9.7 % of the CXD group ( chi 2-test , P less than 0.05 ) . In the assessment of clinical usefulness as well , no significant difference was observed between the 2 groups . In the assessment of overall effects based on the patients whose isolated organisms were sensitive to the drugs , CEX group had more patients not responding to the treatment of acute exacerbation of chronic suppurative otitis media ( chi 2-test , P less than 0.05 ) . Bacteriological effects were not significantly different between the 2 drugs in both acute suppurative otitis media and acute exacerbation of chronic suppurative otitis media . Overall safety rating was not significantly different between the 2 drugs . Side effects occurred as the symptoms of digestive organ in 2 patients each in both groups ( equally an incidence of 2.6 % ) . As for the improvement of each symptom after treatment ( assessed on day 3 ) , CXD was superior in the improvement rate of otorrhea volume as the main symptom of acute exacerbation of chronic suppurative otitis media , while CEX was superior in that of otoobstruction feeling . From the above findings , it is presumed that CXD is a safe drug which can exhibit equal or superior therapeutic effects to CEX in the treatment of acute suppurative otitis media and acute exacerbation of chronic suppurative otitis media , at 3/4 of the CEX dose level An open multicentre study was conducted in 484 children between the ages of 6 months and 12 years with otitis media to compare the efficacy , the safety and the tolerance of once-daily azithromycin given for three days versus thrice-daily amoxicillin/clavulanic acid ( CA ) given for ten days . A satisfactory response ( cure plus improvement ) was noted 10 to 14 days after the start of treatment in 199 of 215 ( 92.6 % ) azithromycin-treated children and in 186 of 198 ( 93.9 % ) amoxicillin/CA-treated children . The relationship between treatment and clinical response was independent of chronicity of infection and the presence or absence of a perforated eardrum . Improvement in signs and symptoms of otitis media occurred significantly more rapidly in the children treated with azithromycin . Treatment-related or possibly treatment-related adverse events were recorded in 11 of 243 ( 4.5 % ) azithromycin-treated patients and in 20 of 240 ( 8.3 % ) treated with amoxicillin/CA . No patients in the azithromycin treatment group were withdrawn from treatment , but six amoxicillin/CA patients , including two < 2 years of age , discontinued treatment prematurely because of adverse events ; the difference between treatment groups was statistically significant ( p=0.0146 ) . It is concluded that azithromycin given as an oral suspension once daily for three days is as safe and effective as amoxicillin/CA given thrice daily for ten days in the treatment of children with otitis media ABSTRACT Infants and young children , especially those in day care , are at risk for recurrent or persistent acute otitis media ( AOM ) . There are no data on oral alternatives to high-dose amoxicillin-clavulanate for treating AOM in these high-risk patients . In this double-blind , double-dummy multicenter clinical trial , we compared a novel , high-dose azithromycin regimen with high-dose amoxicillin-clavulanate for treatment of children with recurrent or persistent AOM . Three hundred four children were r and omized ; 300 received either high-dose azithromycin ( 20 mg/kg of body weight once a day for 3 days ) or high-dose amoxicillin-clavulanate ( 90 mg/kg divided twice a day for 10 days ) . Tympanocentesis was performed at baseline ; clinical response was assessed at day 12 to 16 and day 28 to 32 . Two-thirds of patients were aged ≤2 years . A history of recurrent , persistent , or recurrent plus persistent AOM was noted in 67 , 18 , and 14 % of patients , respectively . Pathogens were isolated from 163 of 296 intent-to-treat patients ( 55 % ) . At day 12 to 16 , clinical success rates for azithromycin and amoxicillin-clavulanate were comparable for all patients ( 86 versus 84 % , respectively ) and for children aged ≤2 years ( 85 versus 79 % , respectively ) . At day 28 to 32 , clinical success rates for azithromycin were superior to those for amoxicillin-clavulanate for all patients ( 72 versus 61 % , respectively ; P = 0.047 ) and for those aged ≤2 years ( 68 versus 51 % , respectively ; P = 0.017 ) . Per-pathogen clinical efficacy against Streptococcus pneumoniae and Haemophilus influenzae was comparable between the two regimens . The rates of treatment-related adverse events for azithromycin and amoxicillin-clavulanate were 32 and 42 % , respectively ( P = 0.095 ) . Corresponding compliance rates were 99 and 93 % , respectively ( P = 0.018 ) . These data demonstrate the efficacy and safety of high-dose azithromycin for treating recurrent or persistent AOM In r and omized , double-blind trials of antibiotic therapy for acute otitis media that determined both clinical and bacteriologic outcomes , clinical success rates were ( 93 % ) 236 of 253 for patients with bacteriologic success , ( 62 % ) 25 of 40 for those with bacteriologic failure , and ( 80 % ) 124 of 155 for those with nonbacterial acute otitis media . These rates were used to calculate the effectiveness of three strategies for assessing drug efficacy : ( 1 ) tympanocentesis and culture before and during therapy ( bacteriologic efficacy ) , ( 2 ) tympanocentesis before therapy and assessment of clinical efficacy in bacterial acute otitis media , and ( 3 ) no tympanocentesis and assessment of clinical efficacy in clinical ( total ) acute otitis media . For a drug with a bacteriologic efficacy of 100 % , calculated clinical efficacy was 93 % for bacterial acute otitis media and 89 % for clinical acute otitis media . For a drug with bacteriologic efficacy of 27 % , a rate consistent with no antibacterial therapy , efficacy was 71 % for bacterial acute otitis media and 74 % for clinical acute otitis media . We conclude that if efficacy is measured by symptomatic response , drugs with excellent antibacterial activity will appear less efficacious than they really are and drugs with poor antibacterial activity will appear more efficacious than they really are . The predominant phenomenon is that drugs with poor antibacterial activity will appear to be clinical ly effective in the treatment of acute otitis media Abstract Objective To assess the efficacy of three days versus five days of treatment with oral amoxicillin for curing non-severe pneumonia in children . Design R and omised , double blind , placebo controlled multicentre trial . Setting Outpatient departments of seven referral hospitals in India . Participants 2188 children aged 2 - 59 months , 1095 given three days of treatment and 1093 given five days . Intervention Oral amoxicillin 31 - 54 mg/kg/day in three divided doses . Main outcome measures Treatment failure : defined as development of chest indrawing , convulsions , drowsiness , or inability to drink at any time ; respiratory rate above age specific cut points on day 3 or later ; or oxygen saturation by pulse oximetry < 90 % on day 3 . Results The clinical cure rates with three days and five days of treatment were 89.5 % and 89.9 % , respectively ( absolute difference 0.4 ( 95 % confidence interval - 2.1 to 3.0 ) ) . Adherence to treatment regimen was 94 % and 85 % for three day and five day treatments , respectively . Loss to follow up was 5.4 % by day 5 . There were no deaths , 41 hospitalisations , and 36 minor adverse reactions . There were 225 ( 10.3 % ) clinical failures and 106 ( 5.3 % ) relapses , and rates were similar in both treatments . At enrolment , 513 ( 23.4 % ) children tested positive for respiratory syncytial virus , and Streptococcus pneumoniae and Haemophilus influenzae were isolated from the nasopharynx in 878 ( 40.4 % ) and 496 ( 22.8 % ) children , respectively . Clinical failure was associated with isolation of respiratory syncytial virus ( adjusted odds ratio 1.95 ( 95 % confidence interval 1.0 to 3.8 ) ) , excess respiratory rate of > 10 breaths/minute ( 2.89 ( 1.83 to 4.55 ) ) , and non-adherence with treatment at day 5 ( 11.57 ( 7.4 to 18.0 ) ) . Conclusions Treatment with oral amoxicillin for three days was as effective as for five days in children with non-severe pneumonia Abstract Two hundred and fifteen children aged 4 months–6 years with acute otitis media ( AOM ) were r and omized to be treated either by a single i.m . injection of ceftriaxone , 50 mg/kg , with a second dose in the event of unsatisfactory response after 48 h or a history of recurrent AOM ( 109 patients ) or amoxicillin clavulanate 12.5 mg tid ( 106 patients ) . The failure rate was similar in children treated by ceftriaxone and amoxicillin clavulanate , 4.6 % and 4.7 % , respectively ( st and ard error for intergroup difference −2.87 % , 95 % confidence interval −5.62 % to 5.87 % ) . No significant differences between the groups were found in the dynamics of the resolution of the acute symptomatology , otoscopy findings , relapse rate at 30 days or tympanographic evidence of middle ear effusion at the scheduled visits on days 30 , 60 and 90 . Recurrence of AOM between days 31 and 90 was observed significantly in more children treated with amoxicillin clavulanate than with ceftriaxone – 25 out of 84 ( 29.4 % ) versus 11 out of 81 ( 13.6 % ) ( P=0.012 ) . Conclusion Ceftriaxone injection(s ) is as efficient at least as 10-day oral amoxicillin clavulanate for Output:	Conclusion There is no evidence of an increased risk of treatment failure with short course of antibiotics for acute otitis media . Among the short-course regimens , azithromycin use was associated with a lower risk of treatment failure while short-acting oral antibiotics and parenteral ceftriaxone may be associated with a higher risk of treatment failure
MS2708	*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 a nurse-led management plan and care pathway for older people discharged from an Accident and Emergency Department after a fall . DESIGN r and omized controlled trial . SETTING a large teaching hospital . SUBJECTS 348 consecutive patients aged 65 or over attending the Accident and Emergency Department with a fall . INTERVENTIONS we r and omized patients to falls nurse intervention or usual care . Within 4 weeks , the intervention group received a home assessment to address easily modifiable risk factors for falls . This included assessment s of medication , ECG , blood pressure , cognition , visual acuity , hearing , vestibular dysfunction , balance , mobility , feet and footwear . All patients were given advice and education about general safety in the home . MAIN OUTCOME MEASURES Further falls , functional ability , re-attendance at the Accident and Emergency Department and admission to hospital . RESULTS at 6 months post-Index fall , 36 patients in the intervention group and 39 patients in the control group had had 89 and 145 falls respectively . Although the intervention group had less falls , this was not significant ( P>0.05 ) . Similarly , the intervention group had fewer fall-related admissions and bed days ( 8 and 69 respectively ) than the control group ( 10 and 233 respectively ) . The intervention group scored significantly higher in indicators of function ( P<0.05 ) and mobility within the community ( P<0.02 ) . CONCLUSIONS although the differences were not significant , patients in the intervention group had fewer falls , less hospital attendances and spent less time in hospital . Moreover , patients in the intervention group were more functionally independent at 6 months post-Index fall STUDY OBJECTIVE In the causative mechanism of falls among older community dwellers , slips and trips have been found to be significant precursors . The purpose of the two year trial was to assess the effectiveness of multi-component interventions targeting major risk factors for falls in reducing the incidence of slips , trips and falls among the well , older community . DESIGN Four groups with approximately equal numbers of participants were r and omly allocated to interventions . The prevention strategies included education and awareness raising of falls risk factors , exercise sessions to improve strength and balance , home safety advice to modify environmental hazards , and medical assessment to optimise health . The interventions combined the strategies in an add on approach . The first intervention group receiving the information session only was regarded as the control . The outcome of interest was the occurrence of a slip , trip or fall , monitored prospect ively using a daily calendar diary . PARTICIPANTS AND SETTING Two hundred and fifty two members of the National Seniors Association in the Brisbane district agreed to participate . National Seniors clubs provide a forum for active , community dwelling Australians aged 50 and over to participate in policy , personal development and recreation . MAIN RESULTS Using Cox 's proportional hazards regression model , adjusted hazard ratios comparing intervention groups with the control ranged from 0.35 ( 95 % CI 0.17 , 0.73 ) to 0.48 ( 0.25 , 0.91 ) for slips ; 0.29 ( 0.16 , 0.51 ) to 0.45 ( 0.27 , 0.74 ) for trips ; and 0.60 ( 0.36 , 1.01 ) to 0.82 ( 0.51 , 1.31 ) for falls . While calendar monitoring recorded outcome , it was also assessed as a prevention strategy by comparing the intervention groups with a hypothetical non-intervened group . At one year after intervention , reductions in the probability of slips , trips and falls ( 61(95%CI 54 , 66)% ; 56 ( 49 , 63)% ; 29 ( 22 , 36)% respectively ) were demonstrated . CONCLUSIONS This study makes an important contribution to the priority community health issue of falls prevention by showing that effective , sustainable , low cost programmes can be introduced through community-based organisations to reduce the incidence of slips , trips and falls in well , older people BACKGROUND Falls in elderly people are a common presenting complaint to accident and emergency departments . Current practice commonly focuses on the injury , with little systematic assessment of the underlying cause , functional consequences , and possibilities for future prevention . We undertook a r and omised controlled study to assess the benefit of a structured inderdisciplinary assessment of people who have fallen in terms of further falls . METHODS Eligible patients were aged 65 years and older , lived in the community , and presented to an accident and emergency department with a fall . Patients assigned to the intervention group ( n=184 ) underwent a detailed medical and occupational-therapy assessment with referral to relevant services if indicated ; those assigned to the control group ( n=213 ) received usual care only . The analyses were by intention to treat . Follow-up data were collected every 4 months for 1 year . FINDINGS At 12-month follow-up , 77 % of both groups remained in the study . The total reported number of falls during this period was 183 in the intervention group compared with 510 in the control group ( p=0.0002 ) . The risk of falling was significantly reduced in the intervention group ( odds ratio 0.39 [ 95 % CI 0.23 - 0.66 ] ) as was the risk of recurrent falls ( 0.33 [ 0.16 - 0.68 ] ) . In addition , the odds of admission to hospital were lower in the intervention group ( 0.61 [ 0.35 - 1.05 ] ) whereas the decline in Barthel score with time was greater in the control group ( p<0.00001 ) . INTERPRETATION The study shows that an interdisciplinary approach to this high-risk population can significantly decrease the risk of further falls and limit functional impairment The importance of environmental hazards in the home as risk factors for falls and fractures is uncertain . A case-control study was conducted , involving people aged 65 years and over referred to an occupational therapy department for home assessment . There were 52 subjects with a recent hip fracture , 43 fallers ( subjects with two or more falls in the past year but no hip fracture ) , and 157 non-fallers ( subjects without hip fracture and with fewer than two falls in the past year ) . Subjects ' homes were assessed for environmental hazards by occupational therapists using a structured home assessment form comprising 35 potential hazards . Overall , the homes of fallers were no more hazardous than the homes of non-fallers . However , fallers with cognitive impairment had significantly more hazards in their homes than non-fallers with cognitive impairment . A wide range of environmental hazards was associated with hip fractures . Many of the findings of this study could be due to bias inherent in the case-control design . To overcome the inadequacies of observational studies for the investigation of home hazards and falls , r and omized trials are recommended to determine if removing hazards reduces the risk of falls and fractures OBJECTIVES To evaluate the effectiveness of a multifaceted , nonpharmaceutical intervention on incidence of falls and fallers . DESIGN Prospect i ve , cluster-r and omized , controlled 12-month trial . SETTING Six community nursing homes in Germany . PARTICIPANTS Long-stay residents ( n = 981 ) aged 60 and older ; mean age 85 ; 79 % female . INTERVENTIONS Staff and resident education on fall prevention , advice on environmental adaptations , progressive balance and resistance training , and hip protectors . MEASUREMENTS Falls , fallers , and fractures . RESULTS The incidence density rate of falls per 1,000 resident years ( RY ) was 2,558 for the control group ( CG ) and 1,399 for the intervention group ( IG ) ( relative risk ( RR ) = 0.55 , 95 % confidence interval ( CI ) = 0.41 - 0.73 ) . Two hundred forty-seven ( 52.3 % ) fallers were detected in the CG and 188 ( 36.9 % ) in the IG ( RR = 0.75 , 95 % CI = 0.57 - 0.98 ) . The incidence density rate of frequent fallers ( > 2/year ) was 115 ( 24.4 % ) for the CG and 66 ( 13.0 % ) for the IG ( RR = 0.56 , 95 % CI = 0.35 - 0.89 ) . The incidence density rate of hip fractures per 1,000 RY was 39 for the CG and 43 for the IG ( RR = 1.11 , 95 % CI = 0.49 - 2.51 ) . Other fractures were diagnosed with an incidence density rate of 52 per 1,000 RY for CG and 41 per 1,000 RY for IG ( RR = 0.78 , 95 % CI = 0.57 - 1.07 ) . CONCLUSION The incidence density rate of falls and fallers differed considerably between the control and intervention groups . The study was underpowered to demonstrate a significant difference of hip or nonhip fractures . Because of a low fracture rate in both groups , the investigation of fracture rates would have required a larger sample size to detect an effect of the intervention OBJECTIVE To assess the effectiveness of an emergency department (ED)-based home safety intervention on caregivers ' behaviors and practice s related to home safety . METHODS We conducted a r and omized , clinical trial of 96 consecutive caregivers of children who were younger than 5 years and presented to an urban pediatric ED for evaluation of an acute unintentional injury sustained in the home . After completing a structured home safety question naire via face-to-face interview , caregivers were r and omly assigned to receive either comprehensive home safety education and free safety devices or focused , injury-specific ED discharge instructions . Participants were contacted by telephone 2 months after the initial ED visit for repeat administration of the safety question naire . The pretest and posttest question naires were scored such that the accrual of points correlated with reporting of safer practice s. Scores were then normalized to a 100-point scale . The overall safety score reflected performance on the entire question naire , and the 8 category safety scores reflected performance in single areas of home injury prevention ( fire , burn , poison , near-drowning , aspiration , cuts/piercings , falls , and safety device use ) . The main outcome was degree of improvement in safety practice s as assessed by improvement in safety scores . RESULTS The intervention group demonstrated a significantly higher average overall safety score at follow-up than the control group ( 73.3 % + /- 8.4 % vs 66.8 % + /-11.1 ) and significant improvements in poison , cut/piercing , and burns category scores . Caregivers in the intervention group also demonstrated greater improvement in reported use of the distributed safety devices . CONCLUSIONS This educational and device disbursement intervention was effective in improving the home safety practice s of caregivers of young children . Moreover , the ED was used effectively to disseminate home injury prevention information Abstract Objective : To determine the effectiveness of multifactorial intervention after a fall in older patients with cognitive impairment and dementia attending the accident and emergency department . Design : R and omised controlled trial . Participants : 274 cognitively impaired older people ( aged 65 or over ) presenting to the accident and emergency department after a fall : 130 were r and omised to assessment and intervention and 144 were r and omised to assessment followed by conventional care ( control group ) . Setting : Two accident and emergency departments , Newcastle upon Tyne . Main outcome measures : Primary outcome was number of participants who fell in year after intervention . Secondary outcomes were number of falls ( corrected for diary returns ) , time to first fall , injury rates , fall related attendances at accident and emergency department , fall related hospital admissions , and mortality . Results : Intention to treat analysis showed no significant difference between intervention and control groups in proportion of patients who fell during 1 year 's follow up ( 74 % ( 96/130 ) and 80 % ( 115/144 ) , relative risk ratio 0.92 , 95 % confidence interval 0.81 to 1.05 ) . No significant differences were found between groups for secondary outcome measures . Conclusions : Multifactorial intervention was not effective in preventing falls in older people with cognitive impairment and dementia presenting to the accident and emergency department after a fall . What is already known on this topic Multifactorial intervention prevents falls in cognitively normal older people living in the community and in those who present to the accident and emergency department after a fall Fall prevention strategies have not been tested by controlled trials in patients with cognitive impairment and dementia who fall What this study adds No benefit was shown from multifactorial assessment and intervention after a fall in patients with cognitive impairment and dementia presenting to the accident and emergency department The intervention was less effective in these patients than in cognitively normal older Parents of 171 children coming to the Yale-New Haven Hospital Primary Care Center for their 6-month checkup were r and omized into an intervention group ( n = 85 ) and a control group ( n = 86 ) . Parents in the intervention group received a three-part individualized course in child safety that required active parental participation . Parts 1 , 2 , and 3 were given at the 6-month , 9-month , and 12-month well-child visits , respectively . Parents in the control group received routine safety education as provided at well-child visits . The educational phase of the study was completed by 129 families , 65 in the intervention group and 64 in the control group . Safety knowledge , number of hazards in the home , and reported accidents were assessed by a " blinded " community health worker approximately 1 month after the 12-month well-child visit . A total of 109 home Output:	REVIEW ER 'S CONCLUSIONS There is insufficient evidence to determine the effects of interventions to modify environmental home hazards .
MS2709	*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 evaluate the outcome and satisfaction of closed treatment versus open reduction and internal fixation in comminuted clavicular fractures . METHODS Sixty patients with displaced clavicular fractures were r and omized into operative ( 29 patients ) and nonoperative ( 31 patients ) groups . Three patients in the operative group did not accept the surgery , and seven patients in the nonoperative group did not complete the one-year follow-up . Outcomes were assessed using the Disability of the Arm , Shoulder and H and ( DASH ) score , Constant shoulder score , specific questions regarding patients ' final satisfaction , physical examination , measurement of the shortening of the clavicular length , and plain radiographs . RESULTS There was one nonunion in the operative group and one in the nonoperative group . The nonunion in operative group was the result of the only infection in this group . Four malunions were developed in the operative group and nineteen malunions in the nonoperative treatment , ( p<0.001 ) . Three patients in the operative group were completely dissatisfied with their treatment . Eighteen patients in the nonoperative group were partially satisfied . Pain was the main reason for dissatisfaction in this group . The mean shortening of the clavicle was 26.5 mm in the nonoperative group and 4.0 mm in the operative group . The mean DASH score for the operative and nonoperative groups were 8.6 and 21.3 , respectively ( p<0.001 ) ; and the Constant shoulder scores were 89.8 and 78.8 ( p<0.001 ) . CONCLUSION Open reduction and internal fixation of comminuted fractures of the clavicle using a reconstruction plate is an effective treatment modality . Despite the variety of complications , this method has a higher satisfaction rate than conservative treatment Background Clavicle fractures account for around 4 % of all fractures and up to 44 % of fractures of the shoulder girdle . Fractures of the middle third ( or mid-shaft ) account for approximately 80 % of all clavicle fractures . Management of this group of fractures is often challenging and the outcome can be unsatisfactory . In particular it is not clear whether surgery produces better outcomes than non-surgical management . Currently there is much variation in the use of surgery and a lack of good quality evidence to inform our decision . Methods / Design We aim to undertake a multicentre r and omised controlled trial evaluating the effectiveness and safety of conservative management versus open reduction and internal fixation for displaced mid-shaft clavicle fractures in adults . Surgical treatment will be performed using the Acumed clavicle fixation system . Conservative management will consist of immobilisation in a sling at the side in internal rotation for 6 weeks or until clinical or radiological union . We aim to recruit 300 patients . These patients will be followed-up for at least 9 months . The primary endpoint will be the rate of non-union at 3 months following treatment . Secondary endpoints will be limb function measured using the Constant-Murley Score and the Disabilities of the Arm , Shoulder and H and ( DASH ) Score at 3 and 9 months post-operatively . Discussion This article presents the protocol for a multicentre r and omised controlled trial . It gives extensive details of , and the basis for , the chosen methods , and describes the key measures taken to avoid bias and to ensure validity . Trial Registration United Kingdom Clinical Research Network ID : 8665 . The date of registration of the trial is 07/09/2006 . The date the first patient was recruited is 18/12/2007 CONTEXT The Consoli date d St and ards for Reporting of Trials ( CONSORT ) statement was developed to help improve the quality of reports of r and omized controlled trials ( RCTs ) . To date , a paucity of data exists regarding whether it has achieved this goal . OBJECTIVE To determine whether use of the CONSORT statement is associated with improvement in the quality of reports of RCTs . DESIGN AND SETTING Comparative before- and -after evaluation in which reports of RCTs published in 1994 ( pre-CONSORT ) were compared with RCT reports from the same journals published in 1998 ( post-CONSORT ) . We included 211 reports from BMJ , JAMA , and The Lancet ( journals that adopted CONSORT ) as well as The New Engl and Journal of Medicine ( a journal that did not adopt CONSORT and was used as a comparator ) . MAIN OUTCOME MEASURES Number of CONSORT items included in a report , frequency of unclear reporting of allocation concealment , and overall trial quality score based on the Jadad scale , a 5-point quality assessment instrument . RESULTS Compared with 1994 , the number of CONSORT checklist items in reports of RCTs increased in all 4 journals in 1998 , and this increase was statistically significant for the 3 adopter journals ( pre-CONSORT , 23.4 ; mean change , 3.7 ; 95 % confidence interval [ CI ] , 2.1 - 5.3 ) . The frequency of unclear reporting of allocation concealment decreased for each of the 4 journals , and this change was statistically significant for adopters ( pre-CONSORT , 61 % ; mean change , -22 % ; 95 % CI , -38 % to -6 % ) . Similarly , 3 of the 4 journals showed an improvement in the quality score for reports of RCTs , and this increase was statistically significant for adopter journals overall ( pre-CONSORT , 2.7 ; mean change , 0.4 ; 95 % CI , 0.1 - 0.8 ) . CONCLUSION Use of the CONSORT statement is associated with improvements in the quality of reports of RCTs We conducted a prospect i ve , r and omized study to determine if patients with midshaft clavicle fractures would benefit from immediate operative stabilization with a modified Hagie pin in comparison with a matched group treated with nonoperative therapy . At a level II trauma center , patients with closed midshaft clavicle fractures were prospect ively r and omized to receive either operative or nonoperative treatment . Fifty-seven ( 29 operative , 28 nonoperative ) patients were enrolled in the study . Operative patients underwent open reduction and internal fixation of the clavicle using a modified Hagie pin ; nonoperative patients were treated with a sling for comfort . All patients were followed at regular intervals for 1 year . They were evaluated for radiographic healing and complications and were scored with the Single Assessment Numeric Evaluation and L'Insalata instruments . Injury severities and radiographs were not statistically significantly different between the 2 groups . Functional scores in the operative group were slightly higher at 3 weeks , and the nonoperative group had slightly higher scores at 6 months and 1 year . The only statistically significant difference between the groups was at 3 weeks . Percentage follow-up at 1 year was 93 % for the operative group and 82 % for the nonoperative group . One patient in each group developed a nonunion , and 1 patient in each group had a refracture . Complications were higher in the operative group , and most were related to pin prominence at the posterior shoulder . Results of this study suggest that , though patients with midshaft clavicle fractures had higher functional scores at short-term follow-up after internal fixation , functional scores were similar at 6 months and 1 year . In addition , internal fixation with a modified Hagie pin was associated with a higher complication rate BACKGROUND Recent literature supports surgical intervention for shortened , displaced , mid-shaft clavicle fractures . We present the results of a r and omized clinical trial comparing locked intramedullary fixation and plate fixation for short , displaced , mid-shaft clavicle fractures . MATERIAL S AND METHODS Local ethical approval was obtained and power analysis and sample size calculations were performed prior to commencement . Patients r and omized to 2 groups to be treated with either locked intramedullary fixation or plating . Patients regularly followed up to clinical and radiographic union . The primary outcome measure was the Constant score , secondary outcome measures included the Oxford shoulder score , union rate , and complication rates . RESULTS Seventeen patients were r and omized to locked intramedullary fixation and 15 r and omized to plating . Mean age was 29.3 years . Mean follow-up was 12.4 months . There was no significant difference in either Constant scores ( P = .365 ) or Oxford scores ( P = .773 ) . There was 100 % union in both groups . In the intramedullary group , 1 case of soft tissue irritation settled after the pin removal ; 1 pin backed out and was revised . Three superficial wound infections result ed in plate removal and 8 plates ( 53 % ) were removed . DISCUSSION Intramedullary fixation has the theoretical advantage of preserving the periosteal blood supply , but carries the morbidity of pin removal . Clavicle plates are not routinely removed but require greater exposure and may compromise periosteal blood supply . CONCLUSION Both locked intramedullary fixation and plating produce good functional results ; however , metalwork may need to be removed as a second procedure BACKGROUND Time to union is a suspect measure for comparing treatments given the absence of a consensus definition of union , the limited reliability of diagnostic tests , and inconsistency in evaluation times . The purpose of this study was to quantify the variations in union and time to union according to different statistical methods and different approaches to missing data . MATERIAL S AND METHODS Data from a published multicenter , r and omized trial comparing operative and nonoperative treatment of clavicular fractures were reanalyzed . Two main types of missing data were encountered : ( 1 ) lost to follow-up or died before union and ( 2 ) missed appointment . We studied the effect of four statistical methods -comparison of means , comparison of medians , χ(2 ) , and Kaplan-Meier curves-for comparing union or time to union between cohorts for the following scenarios : strict intention-to-treat , intention-to-treat with exclusion of patients with less than 12 months of follow-up , as-treated analysis , and four different imputation methods for missing data . RESULTS Mean and median time to union varied up to 17 % , but comparative statistics consistently demonstrated shorter time to union among operatively treated patients . There were significant differences in the odds ratio , χ(2 ) values , and the number needed to treat ( 8%-62 % ) of union vs nonunion for the three principal analyses . CONCLUSION Different strategies for h and ling missed evaluations seem to influence categoric results ( eg , union or nonunion ) more than continuous measures such as time to union Objectives : To determine the cost-effectiveness of open reduction internal fixation ( ORIF ) of displaced , midshaft clavicle fractures in adults . Design : Formal cost-effectiveness analysis based on a prospect i ve , r and omized , controlled trial . Setting : Eight hospitals in Canada ( seven university-affiliated and one community hospital ) . Patients / Participants : One hundred thirty-two adults with acute , completely displaced , midshaft clavicle fractures . Intervention : Clavicle ORIF versus nonoperative treatment . Main Outcome Measurements : Utilities derived from SF-6D . Results : The base case cost per quality -adjusted life-year ( QALY ) gained for ORIF was $ 65,000 . Cost-effectiveness improved to $ 28,150/QALY gained when the functional benefit from ORIF was assumed to be permanent with cost per QALY gained falling below $ 50,000 when the functional advantage persisted for 9.3 years or more . In other sensitivity analyses , the cost per QALY gained for ORIF fell below $ 50,000 when ORIF cost less than $ 10,465 ( base case cost $ 13,668 ) or the long-term utility difference between nonoperative treatment and ORIF was greater than 0.034 ( base case difference 0.014 ) . Short-term disutility associated with fracture healing also affected cost-effectiveness with the cost per QALY gained for ORIF falling below $ 50,000 when the utility of a fracture treated nonoperatively before union was less than 0.617 ( base case utility 0.706 ) or when nonoperative treatment increased the time to union by 20 weeks ( base case difference 12 weeks ) . Conclusions : The cost-effectiveness of ORIF after acute clavicle fracture depended on the durability of functional advantage for ORIF compared with nonoperative treatment . When functional benefits persisted for more than 9 years , ORIF had a favorable value compared with many accepted health interventions Background The traditional view that the vast majority of midshaft clavicular fractures heal with good functional outcomes following non-operative treatment may be no longer valid for all midshaft clavicular fractures . Recent studies have presented a relatively high incidence of non-union and identified speciic limitations of the shoulder function in subgroups of patients with these injuries . Aim A prospect i ve , multicentre r and omised controlled trial ( RCT ) will be conducted in 21 hospitals in the Netherl and s , comparing fracture consolidation and shoulder function after either non-operative treatment with a sling or a plate fixation . Methods / design A total of 350 patients will be included , between 18 and 60 years of age , with a dislocated midshaft clavicular fracture . The primary outcome is the incidence of non-union , which will be determined with st and ardised X-rays ( Antero-Posterior and 30 degrees caudocephalad view ) . Secondary outcome will be the functional outcome , measured using the Constant Score . Strength of the shoulder muscles will be measured with a h and held dynamometer ( MicroFET2 ) . Furthermore , the health-related Quality of Life score ( ShortForm-36 ) and the Disabilities of Arm , Shoulder and H and ( DASH ) Outcome Measure will be monitored as subjective parameters . Data on complications , bone union , cosmetic aspects and use of painkillers will be collected with follow-up question naires . The follow-up time will be two years . All patients will Output:	Conversely , stiffness or restriction of shoulder movement was more common after conservative treatment ( data from three trials ) . Limited evidence is available from r and omised controlled trials on the relative effectiveness of surgical versus conservative treatment for acute middle third clavicle fractures .
MS2710	*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 characterize anemia in elderly nursing home residents . DESIGN Prospect i ve multiinstitutional cohort study . SETTING Five nursing homes . PARTICIPANTS From retrospective analysis , residents found to be anemic using chart review were prospect ively r and omized . Of the 81 residents enrolled , 60 were anemic . MEASUREMENTS Chart review for medical history and factors related to treatment or history of anemia , extensive laboratory evaluation for causes of anemia , and classification of anemia by two hematologists . RESULTS Among the 60 anemic residents , the causes of anemia were idiopathic ( n=27 ) , iron-deficiency ( n=14 ) , anemia associated with chronic disease ( n=8 ) , anemia of renal insufficiency ( n=6 ) , and other ( n=5 ) . The eryrthropoietin ( EPO ) response to anemia was lower in residents with idiopathic anemia ( IA ) than in those with iron-deficiency anemia , and this correlated with renal function as estimated using calculated creatinine clearance . In this elderly population , advancing age was not correlated with lower EPO response . CONCLUSION IA is common in nursing home residents . A lower EPO response contributes to the high prevalence of anemia in this setting and may be due , in part , to occult renal dysfunction BACKGROUND To accurately determine the causes of anemia and proportion of unexplained anemia in a racially diverse cohort of older adults after a comprehensive and st and ardized evaluation . METHODS We evaluated results from a single-institutional university anemia clinic . Patients with anemia , defined as a hemoglobin less than 13.0 g/dL for men and less than 12.0 g/dL for women , underwent a prospect i ve st and ardized history , physical examination , and laboratory measures , with additional studies including bone marrow examination as indicated . Empiric treatment trials were given for identified deficiencies . RESULTS One hundred and seventy-four primarily community-dwelling adults aged 65 years and older were evaluable . African Americans accounted for 69 % of patients and whites were 27 % . Anemia etiologies included iron deficiency anemia at 25.3 % , anemia of chronic inflammation at 9.8 % , and hematologic malignancy in 7.5 % . Unexplained anemia in the elderly accounted for 43.7 % and predominated in both African Americans and whites . The prevalence of iron deficiency anemia and hematologic malignancies did not differ by race . Unexplained anemia in the elderly showed a consistent phenotype composed of a hypoproliferative mild-to-moderate anemia with suppressed serum erythropoietin . Specifically , erythropoietin levels showed no correlation with hemoglobin concentration in unexplained anemia in the elderly ( r = -.15 , p = .19 ) as opposed to iron deficiency anemia ( r = -.63 , p < .0001 ) . CONCLUSIONS In summary , an intensive hematologic evaluation reveals a wide number of anemia etiologies among older adults , including 7.5 % with hematologic malignancies ; nevertheless , unexplained anemia in the elderly prevails as the most common category in whites and African Americans BACKGROUND In the older population , anemia has been associated with poor outcomes including disability and mortality . Underst and ing the mechanisms leading to anemia is essential to plan better treatment and prevention strategies . We tested the hypothesis that the age-related decline in kidney function is associated with an increased prevalence of anemia and that such an increase is accompanied by a concomitant decrement in erythropoietin levels . METHODS Data were from the InCHIANTI study , a population -based study performed in a sample of community-dwelling older ( > or = 65 years ) persons living in Italy . This analysis included 1005 participants with complete data on hemoglobin and erythropoietin levels and markers of renal function . RESULTS The prevalence of anemia according to the World Health Organization criteria ( hemoglobin level < 12 g/dL for women and < 13 g/dL for men ) was 12.0 % and increased with age in both sexes . After adjusting for age , diseases , and other confounders , only participants with a creatinine clearance ( CrCl ) of 30 mL/min or lower ( < or = 0.50 mL/s ) had a higher prevalence of anemia compared with those with a CrCl higher than 90 mL/min ( > 1.50 mL/s ) ( P<.01 ) . Consistently , participants with a CrCl of 30 mL/min or lower ( < or = 0.50 mL/s ) had significantly lower age- and hemoglobin-adjusted erythropoietin endogenous levels . After excluding men and women with CrCl of 30 mL/min or lower ( < or = 0.50 mL/s ) and adjusting for confounders , we found a trend toward an increase in prevalence of anemia with decreasing renal function ; however , it was not statistically significant . CONCLUSIONS Severe age-related decline in renal function is associated with a reduced erythropoietin secretion and anemia . Whether moderate kidney impairment in older persons is associated with a progressively increasing risk of anemia remains to be determined The reasons for inadequate production of erythropoietin ( EPO ) in patients with ESRD are poorly understood . A better underst and ing of EPO regulation , namely oxygen-dependent hydroxylation of the hypoxia-inducible transcription factor ( HIF ) , may enable targeted pharmacological intervention . Here , we tested the ability of fibrotic kidneys and extrarenal tissues to produce EPO . In this phase 1 study , we used an orally active prolyl-hydroxylase inhibitor , FG-2216 , to stabilize HIF independent of oxygen availability in 12 hemodialysis ( HD ) patients , six of whom were anephric , and in six healthy volunteers . FG-2216 increased plasma EPO levels 30.8-fold in HD patients with kidneys , 14.5-fold in anephric HD patients , and 12.7-fold in healthy volunteers . These data demonstrate that pharmacologic manipulation of the HIF system can stimulate endogenous EPO production . Furthermore , the data indicate that deranged oxygen sensing -- not a loss of EPO production capacity -- causes renal anemia OBJECTIVES To examine whether anemia is associated with a higher incidence of recurrent falls . DESIGN Prospect i ve cohort study . SETTING Community-dwelling sample in The Netherl and s. PARTICIPANTS Three hundred ninety-four participants aged 65 to 88 from the Longitudinal Aging Study Amsterdam . MEASUREMENTS Anemia was defined according to World Health Organization criteria as a hemoglobin concentration less than 12 g/dL in women and less than 13 g/dL in men . Falls were prospect ively determined using fall calendars that participants filled out weekly for 3 years . Recurrent fallers were identified as those who fell at least two times within 6 months during the 3-year follow-up . RESULTS Of the 394 persons , 11.9 % ( 18 women and 29 men ) had anemia . The incidence of recurrent falls was 38.3 % of anemic persons versus 19.6 % of nonanemic persons ( P=.004 ) . After adjustment for sex , age , body mass index , and diseases , anemia was significantly associated with a 1.91 times greater risk for recurrent falls ( 95 % confidence interval=1.09 - 3.36 ) . Poor physical function ( indicated by muscle strength , physical performance , and limitations ) partly mediated the association between anemia and incidence of recurrent falls . CONCLUSION Late-life anemia is common and associated with twice the risk of recurrent falls . Muscle weakness and poor physical performance appear to partly mediate this association PURPOSE Anemia is prevalent in old age and is potentially modifiable , but its effects on physical function have not been determined . We examined whether anemia in older persons increases the risk of subsequent decline in physical function , as measured by objective performance-based tests . METHODS Participants in this 4-year prospect i ve cohort study included 1146 participants , aged 71 years or older , living in Iowa and Washington counties , Iowa . Anemia was defined according to World Health Organization ( WHO ) criteria as a hemoglobin concentration below 12 g/dL in women and below 13 g/dL in men . An assessment of st and ing balance , a timed 2.4-m walk , and a timed test of five chair rises were used to assess physical performance ; these were combined into a 0 ( poor ) to 12 ( excellent ) summary scale . RESULTS After adjustment for baseline performance score , health status , and demographic characteristics , anemia was associated with greater mean decline in physical performance over 4 years ; the adjusted mean decline was 2.3 ( 95 % confidence interval [ CI ] : 1.7 to 2.8 ) in subjects with anemia and 1.4 ( 95 % CI : 1.2 to 1.5 ) in those without anemia ( P = 0.003 ) . The association between anemia and greater physical decline was also present in participants who were free of diseases associated with anemia ( cancer , infectious disease , and renal failure ) , and after adjustment for serum cholesterol , iron , and albumin levels . Persons with borderline anemia , a hemoglobin concentration within 1 g/dL above the WHO criteria , also showed greater mean physical decline ( 1.8 ; 95 % CI : 1.5 to 2.2 ) than did those with higher hemoglobin concentrations ( P = 0.02 ) . CONCLUSION This study suggests that anemia in old age is an independent risk factor for decline in physical performance The aim of this study was to prospect ively determine the etiology of anemia in a cohort of community-dwelling older out patients with a comprehensive hematologic evaluation . Participants were men and women age 65 and older with anemia as defined by World Health Organization criteria recruited from outpatient hematology clinics at Stanford Hospital and Clinics ( SHC ) and Veterans Affairs Palo Alto Health Care System ( VAPAHCS ) . Each participant underwent a history and physical examination , followed by a comprehensive hematologic evaluation , which in all participants included complete blood count , red cell indices , review of the blood smear , and assessment of vitamin B12 , folate , iron status and renal function . Additional evaluation was obtained by clinical providers as per their discretion . 190 participants enrolled and completed the evaluation . Twelve percent of participants had iron deficiency anemia . Of those with iron deficiency in whom there was follow-up information , half normalized their hemoglobin in response to iron repletion , and half did not . Thirty-five percent of participants had unexplained anemia . Those with unexplained anemia had mildly increased inflammatory markers compared to non-anemic controls , and , at the lower hemoglobin ranges had relatively low erythropoietin levels . Sixteen percent of participants were categorized as being " suspicious for myelodysplastic syndrome . " Thus , even with comprehensive hematologic evaluation , unexplained anemia is common in older anemic out patients . Iron deficiency anemia is also common and can be difficult to diagnose , and frequently the anemia is not fully corrected with iron repletion PURPOSE To explore the impact of varying hemoglobin levels on mortality , function , and cognition in a representative population of older persons . METHODS Participants in this prospect i ve cohort study included 1 744 men and women , aged 71 years or older , from a r and om household sample living in Durham and surrounding counties in North Carolina . Hemoglobin levels were obtained from participants at baseline in 1992 . Functional status was measured at the 4-year follow-up interview using Katz and instrumental activities of daily living . Cognition was measured using the Short Portable Mental Status Question naire ( SPMSQ ) . Death was determined by search of the National Death Index , and all deaths through 2000 are included . RESULTS Using World Health Organization ( WHO ) criteria , the prevalence of anemia was 24 % . There was a strong racial difference with an odds ratio , adjusted for age , education , estimated glomerular filtration rate and comorbidity of 3.0 ( 95 % CI , 2.3 - 3.9 ) in African Americans compared with Caucasians . The risk ratio for 8-year mortality was 1.7 ( 95 % CI , 1.5 - 2.0 ) for anemic subjects ( P = .0001 ) and did not differ by sex or race . Anemia was strongly associated with poorer physical function ( P = .0001 ) and cognitive function ( P = .0001 ) , and predicted decreases in both over a 4-year period . CONCLUSIONS In an elderly community-based population , anemia is more prevalent in African Americans and is independently associated with increased mortality over 8 years for both races and sexes . Anemia also is a risk factor for functional and cognitive decrease Output:	Conclusion : Our findings suggest that erythropoietin levels in AUE , although elevated , remain inappropriately low , particularly when compared with other forms of anemia . This suggests a relative erythropoietin deficiency or a blunted erythroid cell response
MS2711	*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 benefit of regular multidimensional assessment of older people remains controversial . The majority of trials have been too small to produce adequate evidence to inform policy . Despite the lack of a firm evidence base , UK primary care practitioners ( general practitioners ) are required to offer an annual health check to patients aged 75 years and over . Design Cluster-r and omised factorial trial in primary care comparing a package of assessment s ( i ) universal versus targeted assessment and ( ii ) management by the primary care team ( PC ) or a multidisciplinary geriatric assessment team ( GM ) . The unit of r and omization is the general practice . Methods Older people aged 75 and over eligible for the over 75s health check and excluding those in nursing homes or terminally ill were invited to participate . All participants receive a brief assessment covering all areas of the over 75s check . In the universal arm all participants also receive a detailed health and social assessment by a study nurse while in the targeted arm only participants with a pre-determined number and range of problems at the brief assessment go on to have the detailed assessment . The study nurse follows a st and ard protocol based on results and responses in the detailed assessment to make referrals to ( i ) the r and omised management team ( PC or GM ) ( ii ) other medical services , health care workers or agencies ( iii ) emergency referrals to the GP . The main outcomes are mortality , hospital and institutional admissions and quality of life . 106 practice s and 33,000 older people have been recruited to the trial Aims : There is ongoing debate over the effectiveness of preventive home visits ( PHVs ) for the elderly . A municipality in the north of Sweden carried out a controlled trial of such visits . Healthy seniors aged 75 years and over received two PHVs per year over 2 years . The aim of this study was to do a cost utility analysis of the intervention . Methods : The intervention group ( n=196 ) was compared with a control group ( n=346 ) , and a cost utility analysis was performed . The analysis was carried out with three different time perspectives . Data were source d from official documents and medical and social records . Results : From a societal perspective , using a time period of 4 years , the analysis of PHVs to healthy seniors showed net savings . When including estimated future costs for health and elderly care during gained life years , the result changed from a net saving to a cost of Euro 200,000 . A lifetime perspective also result ed in net savings if the costs of future health and elderly care were not included in the analysis . In this case , the total costs rose to approximately Euro 900,000 . The cost could also be expressed as Euro 14,200 per quality -adjusted life year gained if future costs for elderly care and healthcare were included . Conclusions : PHVs represent a cost-effective intervention in this setting . The costs are justified by the outcomes Objective To quantify the psychological impact of primary care based stepwise screening for type 2 diabetes . Design Controlled trial and comparative study embedded in a r and omised controlled trial . Setting 15 practice s ( 10 screening , five control ) in the ADDITION ( Cambridge ) trial in the east of Engl and . Participants 7380 adults ( aged 40 - 69 ) in the top fourth for risk of having undiagnosed type 2 diabetes ( 6416 invited for screening , 964 controls ) . Interventions Invited for screening for type 2 diabetes or not invited ( controls ) , incorporating a comparative study of subgroups of screening attenders . Attenders completed question naires after a r and om blood glucose test and at 3 - 6 months and 12 - 15 months later . Controls were sent question naires at corresponding time points . Non-attenders were sent question naires at 3 - 6 months and 12 - 15 months . Main outcome measures State anxiety ( Spielberger state anxiety inventory ) , anxiety and depression ( hospital anxiety and depression scale ) , worry about diabetes , and self rated health . Results No significant differences were found between the screening and control participants at any time — for example , difference in means ( 95 % confidence intervals ) for state anxiety after the initial blood glucose test was −0.53 , −2.60 to 1.54 , at 3 - 6 months was 1.51 ( −0.17 to 3.20 ) , and at 12 - 15 months was 0.57 , −1.11 to 2.24 . After the initial test , compared with participants who screened negative , those who screened positive reported significantly poorer general health ( difference in means −0.19 , −0.25 to −0.13 ) , higher state anxiety ( 0.93 , −0.02 to 1.88 ) , higher depression ( 0.32 , 0.08 to 0.56 ) , and higher worry about diabetes ( 0.25 , 0.09 to 0.41 ) , although effect sizes were small . Small but significant trends were found for self rated health across the screening subgroups at 3 - 6 months ( P=0.047 ) and for worry about diabetes across the screen negative groups at 3 - 6 months and 12 - 15 months ( P=0.001 ) . Conclusions Screening for type 2 diabetes has limited psychological impact on patients . Implementing a national screening programme based on the stepwise screening procedure used in the ADDITION ( Cambridge ) trial is unlikely to have significant consequences for patients ' psychological health . Trial registration Current Controlled Trials IS RCT N99175498 Cluster r and omization trials are increasingly being used in primary care research . The main feature of these trials is that patients are nested within large clusters such as physician practice s or communities and the intervention is applied to the cluster . This study design necessitates calculation of intraclass correlation coefficients in order to determine the required sample size . The purpose of this study is to determine intraclass correlation coefficients for a number of outcome measures at the primary care practice level . The CEART study is a r and omized trial testing the effectiveness of translating ATP III guidelines into clinical practice , with primary care physician practice s as the unit of r and omization and patients as the unit of data collection . The intraclass correlation coefficient ( ICC ) was<0.02 and the design effect ranged from 1.0 to 2.3 , respectively , for weight , total cholesterol , LDL , non-HDL , glucose , creatinine , and % at non-HDL goal . For smoking status , body mass index , systolic blood pressure , HDL cholesterol triglycerides , total cholesterol/HDL ratio and % at LDL goal , the ICC was 0.02 - 0.047 and the design effect was 2.6 - 4.1 . The largest ICCs ( 0.05 - 0.12 ) and design effects ( 4.4 - 9.4 ) were found for height and diastolic blood pressure . These findings suggest that cluster r and omization may substantially increase the sample size necessary to maintain adequate statistical power for selected outcomes such as diastolic blood pressure studies compared with simple r and omization for most outcomes evaluated in this study where the design effect is small to moderate . Overall , the ICCs presented will be useful in calculating sample sizes at the primary care level Aim : The aim of this article is to describe the program and study design of our preventive home visit model that targets the specific care needs of Japanese ambulatory frail elders living at home . Methods : The program focused on ambulatory frail elders who were certified as being in the two lowest levels of care need in the Long-Term Care Insurance system and eligible for care , but who were currently not using long-term care services . To provide efficient community-based preventive care , we developed a program model composed of structured assessment s and individualized care recommendations conducted by community care nurses or workers . The assessment protocol focused on locomotion , activities of daily living , social activities , health status , and possibility of abuse . Care needs were clarified every six months over two years . The effectiveness of the program is being assessed in a r and omized controlled trial . Results : A total of 243 elders were assigned r and omly to the preventive home-visit intervention ( n=122 ) or control group ( n=121 ) . Their mean age was 80 years , 76 % were women , and 25 % lived alone . Outcomes including ADLs , IADLs , depression , and social support were measured by postal question naire at baseline , and at 12- and 24-month follow-ups . Utilization of public health or long-term care insurance and service uses over the period is also being documented . Conclusions : The design ’s unique elements of regular evaluation of healthcare needs for targeted individuals within the long-term care insurance context will allow new underst and ing of the role and effectiveness of preventive home visits Objectives To assess whether screening improves the detection of atrial fibrillation ( cluster r and omisation ) and to compare systematic and opportunistic screening . Design Multicentred cluster r and omised controlled trial , with subsidiary trial embedded within the intervention arm . Setting 50 primary care centres in Engl and , with further individual r and omisation of patients in the intervention practice s. Participants 14 802 patients aged 65 or over in 25 intervention and 25 control practice s. Interventions Patients in intervention practice s were r and omly allocated to systematic screening ( invitation for electrocardiography ) or opportunistic screening ( pulse taking and invitation for electrocardiography if the pulse was irregular ) . Screening took place over 12 months in each practice from October 2001 to February 2003 . No active screening took place in control practice s. Main outcome measure Newly identified atrial fibrillation . Results The detection rate of new cases of atrial fibrillation was 1.63 % a year in the intervention practice s and 1.04 % in control practice s ( difference 0.59 % , 95 % confidence interval 0.20 % to 0.98 % ) . Systematic and opportunistic screening detected similar numbers of new cases ( 1.62 % v 1.64 % , difference 0.02 % , −0.5 % to 0.5 % ) . Conclusion Active screening for atrial fibrillation detects additional cases over current practice . The preferred method of screening in patients aged 65 or over in primary care is opportunistic pulse taking with follow-up electrocardiography . Trial registration Current Controlled Trials IS RCT N19633732 OBJECTIVES To apply and evaluate the effects of a program for computer generated physician reminders , integrated with an electronic patient record ( EPR ) system , for opportunistic health screening in elderly patients . DESIGN A pilot study design ed as a 20-month clinical trial with a control group and a 20-month non-intervention follow-up using a computer reminder program that selects patients for screening in five intervention areas ( diabetes , hypertension , cobalamin deficiency , hypothyroidism and anaemia ) . SETTING Four primary health care ( PHC ) centres in suburban Stockholm . SUBJECTS The intervention was design ed for patients 70 years or older from one health care centre who visited a general practitioner ( GP ) during the first 20-month period . Patients from the three remaining centres served as controls . MAIN OUTCOME MEASURES The number of patients who underwent the tests , who had pathological test results , new diagnoses and new pharmacological treatments in both patient groups . RESULTS In total , 602 patients underwent screening and 1989 were controls . There was a statistically significant , moderate or marked increase ( 13 - 75 % ) in the number of patients who were tested in all five intervention areas . An increase in pathological test results ( 1 - 8 % ) was found in two areas : hypertension and cobalamin deficiency . There was an increase in the number of patients with the diagnosis of cobalamin deficiency during the study . At follow-up a decrease in new diagnoses for anaemia was found . CONCLUSION The system seems to be associated with a moderate to large increase in laboratory and manual screening tests for both established and new screening areas . The effect on clinical outcomes was found mainly in a not-yet-established screening area ( cobalamin deficiency ) , indicating that the system may be clinical ly useful when introducing new screening services Multiphasic screening as a case-finding tool was evaluated in a r and omized , controlled study . For each of 112 physicians , a patient was assigned to one of three groups : multiphasic screening group ( SG ) , chart abstract group ( AG ) , or chart review group ( RG ) . Medical problem lists constructed before and after receiving additional information were compared . Physicians for 36 SG patients identified considerably more new medical problems , both total ( 77 ) and ones they considered important ( 25 ) , than 40 AG physicians ( 14 and 8) and 36 RG physicians ( 4 and 0 ) . One year later , 38 of the 95 newly identified problems had been acted on , 31 in the SG . Medical care was affected in nine patients : six in SG , two in AG , and one in RG . Multiphasic screening may help physicians identify new medical problems in clinic patients Background The global burden of the major vascular diseases is projected to rise and to remain the dominant non-communicable disease cluster well into the twenty first century . The Department of Health in Engl and has developed the NHS Health Check service as a policy initiative to reduce population vascular disease risk . The aims of this study were to monitor population changes in cardiovascular disease ( CVD ) risk factors over the first year of the new service and to assess the value of tailored lifestyle support , including motivational interview with ongoing support and referral to other services . Methods R and omised trial comparing NHS Health Check service only with NHS Health Check service plus additional lifestyle support in Stoke on Trent , Engl and . Thirty eight general practice s and 601 ( 365 usual care , 236 additional lifestyle support ) patients were recruited and r and omised independently between September 2 Output:	General health checks are unlikely to be beneficial
MS2712	*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 and hypothesisWe evaluated patients ’ perception and satisfaction with nonsurgical pulsed magnetic stimulation ( PMS ) for treatment of female stress urinary incontinence ( SUI ) in a r and omized , double-blind , sham-controlled trial . Methods Women with SUI ( n = 120 ) were r and omized to either active or sham PMS for 8 weeks ( twice/week ) . Patients answered seven questions on their perception and acceptability , each measured on a 5-point Likert scale . Treatment satisfaction was assessed using two parameters : ( i ) the single-item question “ Overall , please rate how satisfied you are with the treatment ” and ( ii ) Patient Global Impression of Improvement ( PGI-I ) . All adverse events were documented . Results A total of 115 patients completed treatments ( active : n = 57 , sham : n = 58 ) . There were no significant differences between groups in all parameters regarding perception and acceptability ( p > 0.05 ) . In terms of treatment satisfaction , a significantly higher proportion of patients in the active group ( n = 47/57 , 82.4 % ) were either mostly or completely satisfied compared with those in the sham group ( n = 27/58 , 46.6 % ) ( ( p = 0.001 ) . Similarly , a statistically significantly higher percentage of patients in the active group ( n = 39/57 , 68.4 % ) felt much or very much better compared with patients in the sham group ( n = 11/58 , 19.0 % ) as measured using the PGI-I ( p < 0.001 ) . Three ( 5.3 % ) patients in the active group and five ( 8.6 % ) in the sham group experienced adverse events ( p = 0.72 ) . Regardless of treatment arms , 109 ( 94.8 % ) patients would not consider surgical options even if they required further treatment for their condition . Conclusion PMS was well accepted , well tolerated , and result ed in a high treatment satisfaction among women with SUI Purpose : The cough stress test is a common and accepted tool to evaluate stress urinary incontinence but there is no agreement on how the test should be performed . We assessed the diagnostic ability of different cough stress tests performed when varying patient position and bladder volume using urodynamic stress urinary incontinence as the gold st and ard . The 24‐hour pad test was also evaluated . Material s and Methods : We recruited women who presented to specialty outpatient clinics with the complaint of urinary incontinence and who were recommended to undergo urodynamic testing . A total of 140 patients were r and omized to 4 cough stress test groups , including group 1—a comfortably full bladder , group 2—an empty bladder , group 3— a bladder infused with 200 cc saline and group 4—a bladder filled to half functional capacity . The sequence of st and ing and sitting was r and omly assigned . The groups were compared by 1‐way ANOVA or the generalized Fisher exact test . The & kgr ; statistic was used to evaluate agreement between the sitting and st and ing positions . The 95 % CIs of sensitivity and specificity were calculated using the Wilson method . ROC analysis was done to evaluate the performance of the 24‐hour pad test . Results : The cough stress test performed with a bladder filled to half functional capacity was the best performing test with 83 % sensitivity and 90 % specificity . There was no statistically significant evidence that the sensitivity or specificity of 1 cough stress test differed from that of the others . The pad test had no significant predictive ability to diagnose urodynamic stress urinary incontinence ( AUC 0.60 , p = 0.08 ) . Conclusions : Cough stress tests were accurate to diagnose urodynamic stress urinary incontinence . The 24‐hour pad test was not predictive of urodynamic stress urinary incontinence and not helpful when used in conjunction with the cough stress test Introduction and hypothesisWe evaluated the effects of pulsed magnetic stimulation ( PMS ) on overall and different aspects of quality of life ( QoL ) in female patients with stress urinary incontinence ( SUI ) . Methods This study involved 120 female SUI subjects aged ≥21 years old r and omized to either active or sham PMS . Treatment involved two PMS sessions per week for 2 months ( 16 sessions ) . After 2 months , subjects could opt for 16 additional sessions regardless of initial r and omization . The primary response criterion was a 7-point reduction in the total score of the International Consultation on Incontinence Question naire-Lower Urinary Tract Symptoms Quality of Life ( ICIQ-LUTSqol ) question naire . Follow-ups were conducted at months 1 , 2 , 5 , 8 , and 14 . Results At 2 months , 35 out of 60 ( 58 % ) subjects in the active arm and 21 out of 60 ( 21 % ) in the sham arm were treatment responders ( ≥7-point reduction ) ( p = 0.006 ) . There was a significant difference in changes in the mean ± SE ICIQ-LUTSqol total score between the active and sham arms ( Mdiff = −8.74 ± 1.25 vs −4.10 ± 1.08 , p = 0.006 ) . At 1-year post-treatment , regardless of number of PMS sessions ( 16 or 32 sessions ) , subjects who received active PMS ( 63 out of 94 , 67 % ) were more likely to be treatment responders compared with subjects who did not receive any active PMS ( 3 out of 12 , 25 % ; p < 0.001 ) . The impact of PMS treatment was the greatest on the “ physical activities ” domain . Conclusions PMS result ed in significant short- and long-term improvements in overall and various physical , social , and psychological aspects of AIMS To evaluate the effect of functional continuous magnetic stimulation ( FCMS ) on urgency incontinence in r and omized , sham-controlled manner . METHODS Thirty-nine patients with urgency incontinence , 16 males and 23 females ( aged 66.0 + /- 16.5 years ) , who were refractory to pelvic floor muscle training ( PFMT ) , were r and omly assigned either to the treatment schedule performing 10-week active treatment , followed by 4-week non-treatment interval and then by 10-week sham treatment ( A-S , n = 20 ) or to that performing the sham treatment first followed by 10-week active treatment ( S-A , n = 19 ) . RESULTS At 10 weeks , the number of leaks/week , the total score of the International Consultation on Incontinence- Question naire : Short Form ( ICIQ-SF ) , and maximum cystometric capacity ( MCC ) were significantly improved as compared with the initial levels ( P < 0.001 , P < 0.001 , and P = 0.003 , respectively ) in the former group , but not in the latter group . Four ( 20.0 % ) patients were cured in the A-S group , while no patient was cured in the S-A group . At the end of the A-S schedule ( 24 weeks of study ) , the effect of the active treatment was still maintained at a significantly improved level , as compared with the initial level . At the end of the S-A schedule , the number of leaks/week was significantly improved as compared with the initial level and with its 10-week level ( P < 0.001 and P = 0.049 , respectively ) , as well as ICIQ-SF total score ( P = 0.001 and P = 0.006 , respectively ) . MCC significantly increased from its initial level ( P = 0.030 ) . CONCLUSION Magnetic stimulation was effective on urgency incontinence in comparison to sham stimulation in this small patient group Purpose : Despite significant differences in success rates between surgical and nonsurgical treatments for female stress urinary incontinence , a few cross‐sectional surveys showed that most patients still prefer the latter . We evaluated the efficacy of the under studied nonsurgical treatment using pulsed magnetic stimulation for female stress urinary incontinence . Material s and Methods : This r and omized , double‐blind , sham controlled study was performed in 120 female subjects at least 21 years old with stress urinary incontinence . Treatment involved pulsed magnetic stimulation for 2 sessions per week for 2 months ( 16 sessions ) . After 2 months , subjects could opt for 16 additional sessions regardless of initial r and omization . The primary response criterion was a 5‐point reduction in the ICIQ‐UI SF ( International Consultation on Incontinence Question naire for Urinary Incontinence‐Short Form ) score . Key secondary response criteria included objective and subjective cure , supplemented by other secondary criteria . Followups were performed at months 1 , 2 , 5 , 8 and 14 . Results : At 2 months 45 of 60 subjects ( 75 % ) in the active arm vs 13 of 60 ( 21.7 % ) in the sham arm were treatment responders ( p < 0.001 ) . After 2 months 24 subjects ( 40 % ) in the active arm and 41 ( 68 % ) in the sham arm elected additional active pulsed magnetic stimulation . At 14 months , subjects who received 32 sessions of active pulsed magnetic stimulation had the highest percentage of treatment responders ( 18 of 24 or 75.0 % ) , followed by those who received 16 sessions ( 26 of 36 or 72.2 % and 28 of 41 or 68.3 % ) and those who did not receive any active pulsed magnetic stimulation ( 4 of 19 or 21.1 % ) ( p < 0.001 ) . Conclusions : The encouraging long‐term response rates show that pulsed magnetic stimulation is an attractive nonsurgical alternative for patients who do not want to undergo surgery OBJECTIVES To evaluate the efficacy and safety of magnetic stimulation for the treatment of urinary incontinence in women with overactive bladder . METHODS A total of 151 women with urgency incontinence were r and omized to the active stimulation group or the sham stimulation group in a 2:1 order . An armchair type magnetic stimulator was used for 25-min magnetic stimulation twice a week , with the maximum magnetic flux density of 560 mT peak at 10 Hz . The sham device was set to deliver in a 5-s " on"-5-s " off " pulsing manner with the maximum intensity of 20.4 % of active stimulation at 1 Hz . The study consisted of a baseline period for 1 week , and a treatment period for 6 weeks . The primary end-point was the number of leaks/week from the bladder diary . The secondary end-points were the number of voids and urgency/24 h , mean and maximum voided volume , and the quality of life assessment . RESULTS Changes from baseline in the active and sham group , respectively , were -13.08 ± 11.00 and -8.68 ± 13.49 in leaks/week ( P = 0.038 ) , -2.65 ± 2.52 and -1.53 ± 2.39 in number of urgency/24 h ( P = 0.011 ) , and 14.03 ± 34.53 mL and -4.15 ± 40.60 mL in mean voided volume ( P = 0.0056 ) . As for safety , except for diarrhea and constipation , no patients experienced any device-related adverse event . CONCLUSIONS Magnetic stimulation is effective for the treatment of urgency incontinence in female patients with overactive bladder Background There is currently a lack of r and omized , sham-controlled trials that are adequately powered , using vali date d outcomes , to allow for firm recommendations on the use of magnetic stimulation for stress urinary incontinence . We report a protocol of a multicenter , r and omized , double-blind , sham-controlled parallel-group trial to evaluate the efficacy of magnetic stimulation for stress urinary incontinence . Methods / Design One hundred twenty subjects with stress urinary incontinence will be r and omized in a 1:1 allocation to either active or sham magnetic stimulation using computer-generated , permuted blocks of variable sizes . Subjects will receive 2 sessions of magnetic stimulation per week for 8 weeks ( 16 sessions total ) . The primary outcome is the improvement in severity of involuntary urine loss based on the International Consultation on Incontinence Question naire for Urinary Incontinence Short Form at the end of treatment sessions compared with baseline . Secondary outcomes include cure , stress urinary incontinence – related symptoms ( incontinence episode frequency , urine loss in 1-hour pad test , pelvic floor muscle strength ) and health-related quality of life ( Patient Global Impression of Improvement , International Consultation on Incontinence Question naire – Lower Urinary Tract Symptoms Quality of Life and EQ-5D ) . The safety of magnetic stimulation will also be assessed . Besides evaluation of clinical treatment effectiveness , cost-effectiveness analysis using patient-reported outcomes will be performed . Discussion This trial is design ed to provide pending outcome information on this non-invasive treatment option . We intend to acknowledge the existing flaws in previous clinical trials and determine conclusively whether magnetic stimulation is effective for stress urinary incontinence . Trial registration Clinical Trials.gov Identifier : NCT01924728 . Date of Registration : 14 August 2013 PURPOSE We design ed an investigational study and placebo controlled trial to evaluate the potential efficacy of magnetic stimulation of the sacral roots for the treatment of stress incontinence . MATERIAL S AND METHODS A total of 75 patients with stress incontinence were studied . A 15 Hz . repetitive magnetic stimulation of the sac Output:	Our meta- analysis preliminarily indicates that MS treatment is an effective therapeutic modality for patients with UI .
MS2713	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: AIMS AND OBJECTIVES To compare drug adherence to lipid-lowering therapy among out patients with coronary artery disease who received information via short message service , via short message service and Micro Letter , or via phone only . BACKGROUND Messaging applications and short message service are commonly used internationally . However , little is known about how coronary artery disease out patients in China may benefit from receiving health education through these technologies . DESIGN R and om sampling method . METHODS Data were collected from March-December 2013 . Subjects from Chengdu City , China , were r and omised to three groups : short message service , short message service + Micro Letter , and phone ( control ) . Appointment reminders and health information were delivered to patients in accordance with design ations . After six months , adherence to statin prescriptions was compared among the groups by using the Morisky Medication Adherence Scale . Logistic regression analysis was applied to determine those independent variables that were related to adherence . RESULTS The short message service and short message service + Micro Letter groups had better cumulative adherence ( lower Morisky Medication Adherence Scale scores ) after six months than phone group , and the short message service + Micro Letter group had better cumulative adherence ( lower Morisky Medication Adherence Scale scores ) than the short message service group . Female sex , older age and marriage show positive associations with adherence . CONCLUSIONS Short message service and messaging applications , such as Micro Letter , are effective means of providing discharged patients with reminders and coronary artery disease-related health information . Implementation of a short message service + Micro Letter program can improve outpatient adherence to medication . RELEVANCE TO CLINICAL PRACTICE This research offers useful information to help medical staff design effective interventions to improve medication compliance among coronary artery disease patients AIM Short message service ( SMS ) is an applied technology of communication that enables the transfer of information and can be used as a part of medical efforts to motivate clients to improve their behavior regarding drug consumption . This study attempts to observe the differences in patients ' behavior as a result of either using SMS to motivate their drug consumption or by using only health providers and outreach workers to monitor them . METHODS This study used a post-test-only controlled-group design with a simple r and om sampling technique and was held in Malang , Indonesia . The sample in this study consisted of 45 patients with tuberculosis ( TB ) who received motivating SMS messages and 45 patients with only health providers and outreach workers to monitor them . RESULTS Fisher 's Exact test using a 95 % confidence interval showed that the result of this study had a P-value of 0.059 , which means that there was no difference in compliance with drug consumption between the patients who received SMS messages and the patients who were under the supervision of health providers and outreach workers . CONCLUSION It is highly recommended that the application of SMS be included in TB treatment and the evaluation of patients as an alternative method of controlling patients ' compliance with consuming anti-TB drugs at home Background Applying mobile phones in healthcare is increasingly prioritized to strengthen healthcare systems . Antenatal care has the potential to reduce maternal morbidity and improve newborns ’ survival but this benefit may not be realized in sub-Saharan Africa where the attendance and quality of care is declining . We evaluated the association between a mobile phone intervention and antenatal care in a re source -limited setting . We aim ed to assess antenatal care in a comprehensive way taking into consideration utilisation of antenatal care as well as content and timing of interventions during pregnancy . Methods This study was an open label pragmatic cluster-r and omised controlled trial with primary healthcare facilities in Zanzibar as the unit of r and omisation . 2550 pregnant women ( 1311 interventions and 1239 controls ) who attended antenatal care at selected primary healthcare facilities were included at their first antenatal care visit and followed until 42 days after delivery . 24 primary health care facilities in six districts were r and omized to either mobile phone intervention or st and ard care . The intervention consisted of a mobile phone text-message and voucher component . Primary outcome measure was four or more antenatal care visits during pregnancy . Secondary outcome measures were tetanus vaccination , preventive treatment for malaria , gestational age at last antenatal care visit , and antepartum referral . Results The mobile phone intervention was associated with an increase in antenatal care attendance . In the intervention group 44 % of the women received four or more antenatal care visits versus 31 % in the control group ( OR , 2.39 ; 95 % CI , 1.03 - 5.55 ) . There was a trend towards improved timing and quality of antenatal care services across all secondary outcome measures although not statistically significant . Conclusions The wired mothers ’ mobile phone intervention significantly increased the proportion of women receiving the recommended four antenatal care visits during pregnancy and there was a trend towards improved quality of care with more women receiving preventive health services , more women attending antenatal care late in pregnancy and more women with antepartum complications identified and referred . Mobile phone applications may contribute towards improved maternal and newborn health and should be considered by policy makers in re source -limited setting s . Trial registration Clinical Trials.gov , NCT01821222 PURPOSE The current malaria treatment in Zambia is more than 97 % effective when the regimen is strictly adhered to . However , the mean adherence rate in sub-Saharan Africa is only 38 % to 48 % . Poor pharmacoadherence remains a significant barrier to malaria control and elimination . The purpose of this study was to determine if adherence rates to a six-dose artemesinin-based combination therapy ( ACT ) treatment differ between patients who received short message service ( SMS ) reminders and those who did not . This is the first study of its kind using SMS directly to the patient for ACT adherence in sub-Saharan Africa . DESIGN An experimental , r and omized controlled trial was conducted through a sample of 96 adult malaria patients at Fisenge Clinic in Zambia in 2014 . METHODS The intervention group received SMS messages to remind them to take their medication according to the prescribed regimen . An electronic pillbox was used to measure pharmacoadherence for both groups , and patients were classified as probably adherent or probably nonadherent . FINDINGS Data were analyzed using chi-square for association between the SMS intervention and pharmacoadherence , and logistic regression was used for predictors of adherence . No significant association was found between SMS reminders and pharmacoadherence ( χ(2 ) = 0.19 , df = 1 , p = .67 ) . Binary logistic regression indicated that there were no variables associated with adherence ( p > .05 ) . CONCLUSIONS SMS reminder messages did not appear to improve pharmacoadherence in malaria medication . CLINICAL RELEVANCE The study indicates few implication s to nursing practice due to the lack of association between SMS and adherence , but adds to current knowledge Objective To evaluate the effectiveness of daily text messages as a means to improve caregivers ’ adherence to infant micronutrient powder ( MNP ) in rural Shaanxi Province of China . Methodology 638 infants aged 6–11 months in 234 villages were involved in a cluster-r and omized controlled trial ( RCT ) . All caregivers were given free infant MNP packets at baseline in April 2013 and the follow-up survey was in July 2013 . We r and omly assigned 318 infants in 117 villages to treatment group ( receiving daily text message ) and 320 infants in the other 117 villages as control group . Results On average , daily text messages increased the number of MNP packets fed ( marginal effect = 4.63 ; 95 % confidence interval ( CI ) = 0.16 , 9.10 ) . The text message is more likely to increase the consumption of MNP packets if the primary caregiver was the mother ( marginal effect = 12.19 ; 95 % CI = 0.69 , 23.68 ) . Receiving the text message appears to significantly increase the likelihood of full adherence when the primary caregiver can either check ( odds ratio = 2.93 ; 95 % CI = 1.34 , 6.40 ) or knows how to send ( odds ratio = 3.26 ; 95 % CI = 1.53 , 6.97 ) text messages . Conclusion Daily text messages improved the consumption of infant MNP packets . However , the impact was not large enough to increase the probability of caregivers being fully adherent to the feeding instruction , which is to feed 5–7 packets per week as recommended . In addition , when the mother is the caregiver and when the caregiver can check or knows how to send text messages there is greater adherence by the primary caregivers . Trial registration http://www.is rct n.com/IS RCT AIMS AND OBJECTIVES To determine the effectiveness of an electronic messaging support service for management of cardiovascular risk factors in patients with diabetes . BACKGROUND Microletter and short message service are widely used , but their health education benefit for people with type 2 diabetes mellitus has not been investigated . DESIGN Convenience sample study with r and omised group assignment . METHODS Participants completed survey question naires , physical and laboratory evaluations between May 2015 and May 2016 and were then r and omly assigned to two groups for receipt of a microletter + short message or a phone call ( control ) . Appointment reminders and health information were sent to the intervention patients by microletter + short message . Every three months , intervention patients and control patients were followed up by telephone . After 12 months , changes in cardiovascular risk factors in each group were evaluated and compared . RESULTS There were no statistically significant changes or between-group differences in daily smoking and drinking . There were statistically significant between-group differences in glycated haemoglobin ( p = .034 ) , postpr and ial plasma glucose ( p = .001 ) , postpr and ial insulin ( p = .005 ) , total cholesterol ( p = .038 ) and low-density lipoprotein ( p < .001 ) . Levels of glycated haemoglobin ( p = .011 ) , fasting plasma glucose ( p = .007 ) , postpr and ial plasma glucose ( p < .001 ) , fasting insulin ( p = 0.004 ) , postpr and ial insulin ( p < .001 ) , total cholesterol ( p < .001 ) and low-density lipoprotein ( p < .001 ) were found to be decreased significantly in intervention patients . Systolic blood pressure decreased significantly in patients only followed by telephone ( p = .014 ) . The microletter + short message intervention was an effective means of reducing cardiovascular risk in patients with type 2 diabetes mellitus . CONCLUSION Regular smartphone communication had a favourable impact on cardiovascular risk factors in patients with type 2 diabetes mellitus . RELEVANCE TO CLINICAL PRACTICE Regular smartphone communication has a favourable impact on cardiovascular risk factors in patients with type 2 diabetes mellitus Background Large investments are currently made in community – based complementary food supplement ( Ying Yang Bao , YYB ) programs to improve nutrition of young children in rural areas in China . However , there is a lack of knowledge about the experience and challenges of implementing YYB programs in China . We aim ed to : 1 ) monitor distribution of YYB ; 2 ) assess children ’s adherence to and acceptability of YYB ; and 3 ) evaluate community – based strategies to improve the program . Methods This mixed methods evaluation study combined data from surveys and focus groups that took place during a controlled interventional evaluation trial . The trial aim ed to evaluate the effectiveness of community – based YYB distribution on improving children 's health status in rural areas in China . We conducted five cross – sectional surveys with caregivers of children aged 6–23 months ( baseline survey ( N = 1804 ) in August 2012 and four follow – up cross – sectional surveys : 1 ) N = 494 in January 2013 ; 2 ) N = 2187 in August 2013 ; 3 ) N = 504 in January 2014 ; and 4 ) N = 2186 in August 2014 ) in one rural county in Qinghai Province . We used a two – stage cluster sampling technique to select mothers with eligible children for each survey . Information was collected from caregivers on household characteristics , YYB consumption and acceptability in the surveys . High adherence in each survey was defined as children who consumed at least four YYB sachets during the previous week . A logistic regression model was developed to obtain odds ratios ( OR ) with 95 % confidence intervals of factors associated with high adherence . Also , we conducted 10 focus groups with73 caregivers and health workers involved in the YYB distribution . Content analysis was used to explore qualitative findings , which were used to gain deeper insight into the quantitative results . Results Around 90 % of caregivers had ever received YYB and more than 80 % of children ever took YYB . Caregivers mainly knew about YYB through their village doctors . High adherence to YYB increased from 49.4 % in the first follow – up survey ( January 2013 ) to 81.4 % in the last follow – up survey ( August 2014 ; P < 0.0001 ) . Repeated training sessions with village doctors could increase adherence . However , due to unplanned YYB stock – out , caregivers did not receive YYB for six months , which may have led to a decrease of high adherence from 64.1 % in the second follow – up survey ( August 2013 ) to 53.6 % in the third follow – up survey ( January 2014 ; P < 0.00 Output:	This systematic review shed light on the most prominent health outcomes that can be improved using mHealth technology interventions in developing countries .
MS2714	*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 Liver fibrosis is an important prognostic factor in patients with hepatitis C. The effect of pegylated ( PEG ) interferon alone or its combination with ribavirin on fibrosis has not been established . METHODS We pooled individual data from 3010 naive patients with pretreatment and posttreatment biopsies from 4 r and omized trials . Ten different regimens combining st and ard interferon , PEG interferon , and ribavirin were compared . The impact of each regimen was estimated by the percentage of patients with at least 1 grade improvement in the necrosis and inflammation ( METAVIR score ) , the percentage of patients with at least 1 stage worsening in fibrosis METAVIR score , and by the fibrosis progression rate per year . RESULTS Necrosis and inflammation improvement ranged from 39 % ( interferon 24 weeks ) to 73 % ( optimized PEG 1.5 and ribavirin ; P < 0.001 ) . Fibrosis worsening ranges from 23 % ( interferon 24 weeks ) to 8 % ( optimized PEG 1.5 and ribavirin ; P < 0.001 ) . All regimens significantly reduced the fibrosis progression rates in comparison to rates before treatment . The reversal of cirrhosis was observed in 75 patients ( 49 % ) of 153 patients with baseline cirrhosis . Six factors were independently associated with the absence of significant fibrosis after treatment : baseline fibrosis stage ( odds ratio [ OR ] = 0.12 ; P < 0.0001 ) , sustained viral response ( OR = 0.36 ; P < 0.0001 ) , age < 40 years ( OR = 0.51 ; P < 0.001 ) , body mass index < 27 kg/m(2 ) ( OR = 0.65 ; P < 0.001 ) , no or minimal baseline activity ( OR = 0.70 ; P = 0.02 ) , and viral load < 3.5 millions copies per milliliter ( OR = 0.79 ; P = 0.03 ) . CONCLUSIONS PEG-interferon and ribavirin combination significantly reduces the rate of fibrosis progression in patients with hepatitis BACKGROUND & AIMS Chronic hepatitis C is both a virologic and fibrotic disease and complications can occur in patients with sustained virologic response ( SVR ) with residual fibrosis . Due to the limitations of repeated biopsies , no studies have assessed the dynamic of fibrosis before and after treatment . Using biopsy as reference , FibroTest ™ has been vali date d as a biomarker of fibrosis progression and regression , with similar prognostic values . The aim was to estimate the impact of SVR on the dynamic of fibrosis presumed by FibroTest ™ . METHODS In a prospect i ve cohort , the main end point was the 10-year regression rate of fibrosis , defined as a minimum 0.20 decrease in FibroTest ™ , equivalent to one METAVIR stage . RESULTS A total of 933 patients with both repeated FibroTest ™ and transient elastography were included . At 10 years , among the 415 patients with baseline advanced fibrosis , 49 % ( 95 % CI 33 - 64 % ) of the 108 SVR had a regression , which was greater than in the 219 non-responders [ 23 % ( 14 - 33 % ; p < 0.001 vs. SVR ) ] and not lower than in the 88 non-treated [ 45 % ( 10 - 80 % ; p = 0.39 vs. SVR ) ] patients . In all 171 SVR , cirrhosis regressed in 24/43 patients , but 15 new cirrhosis cases occurred out of 128 patients , that is only a net reduction of 5.3 % [ ( 24 - 15 ) = 9/171 ) ; ( 2.4 - 9.8 % ) ] . Four cases of primary liver cancer occurred in SVR [ 4.6 % ( 0 - 9.8 ) ] , and 13 in non-responders [ 5.6 % ( 1.5 - 9.8 ) ; p = 0.07 ] . CONCLUSIONS In patients with chronic hepatitis C , and as presumed by FibroTest ™ , virological cure was associated with slow regression of fibrosis 10years later , a disappointing 5 % decrease in cirrhosis cases , and a remaining 5 % risk of primary liver cancer BACKGROUND A sustained virological response ( SVR ) rate of 41 % has been achieved with interferon alfa-2b plus ribavirin therapy of chronic hepatitis C. In this r and omised trial , peginterferon alfa-2b plus ribavirin was compared with interferon alfa-2b plus ribavirin . METHODS 1530 patients with chronic hepatitis C were assigned interferon alfa-2b ( 3 MU subcutaneously three times per week ) plus ribavirin 1000 - 1200 mg/day orally , peginterferon alfa-2b 1.5 microg/kg each week plus 800 mg/day ribavirin , or peginterferon alfa-2b 1.5 microg/kg per week for 4 weeks then 0.5 microg/kg per week plus ribavirin 1000 - 1200 mg/day for 48 weeks . The primary endpoint was the SVR rate ( undetectable hepatitis C virus [ HCV ] RNA in serum at 24-week follow-up ) . Analyses were based on patients who received at least one dose of study medication . FINDINGS The SVR rate was significantly higher ( p=0.01 for both comparisons ) in the higher-dose peginterferon group ( 274/511 [ 54 % ] ) than in the lower-dose peginterferon ( 244/514 [ 47 % ] ) or interferon ( 235/505 [ 47 % ] ) groups . Among patients with HCV genotype 1 infection , the corresponding SVR rates were 42 % ( 145/348 ) , 34 % ( 118/349 ) , and 33 % ( 114/343 ) . The rate for patients with genotype 2 and 3 infections was about 80 % for all treatment groups . Secondary analyses identified bodyweight as an important predictor of SVR , prompting comparison of the interferon regimens after adjusting ribavirin for bodyweight ( mg/kg ) . Side-effect profiles were similar between the treatment groups . INTERPRETATION In patients with chronic hepatitis C , the most effective therapy is the combination of peginterferon alfa-2b 1.5 microg/kg per week plus ribavirin . The benefit is mostly achieved in patients with HCV genotype 1 infections Interferon and ribavirin decrease necroinflammation in chronic hepatitis C with or without virological clearance ; however , reversibility of fibrosis remains to be established . We evaluated the effect of combination therapy on virological and liver histopathological outcomes in 52 naïve patients and 79 patients unresponsive to interferon monotherapy with predominantly genotype 1 chronic hepatitis C. One hundred four patients completed interferon and ribavirin treatment after 24–48 weeks . Fifty-six paired liver biopsies ( mean biopsy interval 28 months ) were assessed by the Ishak score . Sustained virological responses were 37 % in naïve patients and 22 % in re-treated patients . In virological responders and nonresponders , fibrosis and necroinflammation scores decreased by −0.91 ( P = 0.04 ) and −0.5 ( P = 0.02 ) and by −2.8 ( P = 0.001 ) and −0.66 ( P = 0.06 ) , respectively . Interferon and ribavirin had greater benefit on fibrosis when associated with clearance of HCV RNA . Treatment strategies in virological nonresponders who show fibrosis regression should include consideration of maintenance therapy , if such treatment eventually proves to benefit histological outcomes BACKGROUND In phase 2 trials , telaprevir , a hepatitis C virus ( HCV ) genotype 1 protease inhibitor , in combination with peginterferon-ribavirin , as compared with peginterferon-ribavirin alone , has shown improved efficacy , with potential for shortening the duration of treatment in a majority of patients . METHODS In this international , phase 3 , r and omized , double-blind , placebo-controlled trial , we assigned 1088 patients with HCV genotype 1 infection who had not received previous treatment for the infection to one of three groups : a group receiving telaprevir combined with peginterferon alfa-2a and ribavirin for 12 weeks ( T12PR group ) , followed by peginterferon-ribavirin alone for 12 weeks if HCV RNA was undetectable at weeks 4 and 12 or for 36 weeks if HCV RNA was detectable at either time point ; a group receiving telaprevir with peginterferon-ribavirin for 8 weeks and placebo with peginterferon-ribavirin for 4 weeks ( T8PR group ) , followed by 12 or 36 weeks of peginterferon-ribavirin on the basis of the same HCV RNA criteria ; or a group receiving placebo with peginterferon-ribavirin for 12 weeks , followed by 36 weeks of peginterferon-ribavirin ( PR group ) . The primary end point was the proportion of patients who had undetectable plasma HCV RNA 24 weeks after the last planned dose of study treatment ( sustained virologic response ) . RESULTS Significantly more patients in the T12PR or T8PR group than in the PR group had a sustained virologic response ( 75 % and 69 % , respectively , vs. 44 % ; P<0.001 for the comparison of the T12PR or T8PR group with the PR group ) . A total of 58 % of the patients treated with telaprevir were eligible to receive 24 weeks of total treatment . Anemia , gastrointestinal side effects , and skin rashes occurred at a higher incidence among patients receiving telaprevir than among those receiving peginterferon-ribavirin alone . The overall rate of discontinuation of the treatment regimen owing to adverse events was 10 % in the T12PR and T8PR groups and 7 % in the PR group . CONCLUSIONS Telaprevir with peginterferon-ribavirin , as compared with peginterferon-ribavirin alone , was associated with significantly improved rates of sustained virologic response in patients with HCV genotype 1 infection who had not received previous treatment , with only 24 weeks of therapy administered in the majority of patients . ( Funded by Vertex Pharmaceuticals and Tibotec ; ADVANCE Clinical Trials.gov number , NCT00627926 . ) The prognosis of chronic hepatitis C virus ( HCV ) infection is still ill‐defined . The present study prospect ively evaluated mortality and complications in a large cohort of patients with chronic hepatitis C. The study included 838 anti‐HCV and HCV‐RNA – positive patients who were followed for 50.2 ± 26.9 months ( mean ± SD ; range , 6‐122 months ) in a prospect i ve protocol . During follow‐up , 62 patients died ( 31 from liver disease and 31 from other causes ) , and 12 patients needed liver transplantation . When compared with a matched general population , hepatitis C increased mortality mainly when cirrhosis was present and in patients who were less than 50 years old at study entry . During follow‐up , a further 30 patients developed nonlethal complications of cirrhosis . By multivariate regression , survival was decreased by cirrhosis , long disease duration , history of intravenous drug abuse , and excessive alcohol consumption , whereas interferon therapy improved survival . Alanine transaminase ( ALT ) , bilirubin , sex , and genotype had no effect on survival . The risk of hepatocellular carcinoma ( HCC ) ( n = 17 ) was increased by cirrhosis and to a lesser degree by long disease duration and high bilirubin , whereas interferon therapy , genotype , and other factors had no effect . Chronic hepatitis C is a disease with considerable mortality and morbidity when cirrhosis is present at diagnosis . Patients who acquire the infection early in life have a markedly increased mortality even when cirrhosis is absent at diagnosis . The age at diagnosis therefore should play a major role in therapeutic considerations . The present data also suggest that interferon therapy has a long‐term clinical benefit , although it did not reduce the risk of liver cancer BACKGROUND / AIMS Data on hepatitis C virus ( HCV ) viral dynamics and on the effect of interferon in blocking virion production have suggested a rationale for daily administration of interferon in patients with chronic hepatitis C infection . We compared the efficacy and safety of daily interferon alfa-2b in combination with ribavirin with those of interferon alfa-2b three times a week alone or in combination with ribavirin . METHODS We r and omly assigned 321 patients with chronic hepatitis C to receive st and ard-dose interferon alfa-2b alone or in combination with Output:	Conclusions : There could be a favorable characteristic of fibrosis regression in SVR patients . However , residential fibrosis may remain an issue because of a non‐ignorable prevalence of fibrosis maintenance among these patients
MS2715	*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 Patients often seek other patients ’ experiences with the disease . The Internet provides a wide range of opportunities to share and learn about other people ’s health and illness experiences via blogs or patient-initiated online discussion groups . There also exists a range of medical information devices that include experiential patient information . However , there are serious concerns about the use of such experiential information because narratives of others may be powerful and pervasive tools that may hinder informed decision making . The international research network DIPEx ( Data base of Individual Patients ’ Experiences ) aims to provide scientifically based online information on people ’s experiences with health and illness to fulfill patients ’ needs for experiential information , while ensuring that the presented information includes a wide variety of possible experiences . Objective The aim is to evaluate the colorectal cancer module of the German DIPEx website krankheitserfahrungen.de with regard to self-efficacy for coping with cancer and patient competence . Methods In 2015 , a Web-based r and omized controlled trial was conducted using a two-group between-subjects design and repeated measures . The study sample consisted of individuals who had been diagnosed with colorectal cancer within the past 3 years or who had metastasis or recurrent disease . Outcome measures included self-efficacy for coping with cancer and patient competence . Participants were r and omly assigned to either an intervention group that had immediate access to the colorectal cancer module for 2 weeks or to a waiting list control group . Outcome criteria were measured at baseline before r and omization and at 2 weeks and 6 weeks Results The study r and omized 212 persons . On average , participants were 54 ( SD 11.1 ) years old , 58.8 % ( 124/211 ) were female , and 73.6 % ( 156/212 ) had read or heard stories of other patients online before entering the study , thus excluding any influence of the colorectal cancer module on krankheitserfahrungen.de . No intervention effects were found at 2 and 6 weeks after baseline . Conclusions The results of this study do not support the hypothesis that the website studied may increase self-efficacy for coping with cancer or patient competencies such as self-regulation or managing emotional distress . Possible explanations may involve characteristics of the website itself , its use by participants , or method ological reasons . Future studies aim ed at evaluating potential effects of websites providing patient experiences on the basis of method ological principles such as those of DIPEx might profit from extending the range of outcome measures , from including additional measures of website usage behavior and users ’ motivation , and from exp and ing concepts , such as patient competency to include items that more directly reflect patients ’ perceived effects of using such a website . Trial Registration Clinical trials.gov NCT02157454 ; https:// clinical trials.gov/ct2/show/NCT02157454 ( Archived by WebCite at http://www.webcitation.org/6syrvwXxi Background The use of a mobile health care application , the delivery of health care or health care‐related services through the use of portable devices , to manage functional loss , treatment‐related toxicities , and impaired quality of life in cancer patients during chemotherapy through supervised self‐management has been increasing . The aim of the present study was to evaluate the efficacy and feasibility of comprehensive mobile health care using a tailored rehabilitation program for colorectal cancer patients undergoing active chemotherapy . Patients and Methods A total of 102 colorectal cancer patients undergoing chemotherapy underwent 12 weeks of smartphone aftercare through provision of a mobile application and wearable device that included a rehabilitation exercise program and information on their disease and treatment . The grip strength test , 30‐second chair st and test , 2‐minute walk test , amount of physical activity ( International Physical Activity Question naire short‐form ) , quality of life ( European Organization for Research and Treatment of Cancer Quality of Life Question naire C30 ) , and nutritional status ( Patient‐generated Subjective Global Assessment ) were assessed and measured at baseline , at mid‐intervention ( 6 weeks ) , and at completion of the intervention ( 12 weeks ) . The rehabilitation exercise intensity was adjusted by the test results at every assessment and through real‐time communication between the patients and clinicians . Results Of the 102 patients , 75 completed all 12 weeks of the smartphone aftercare rehabilitation program . The lower extremity strength ( P < .001 ) and cardiorespiratory endurance ( P < .001 ) was significantly improved . Fatigue ( P < .007 ) and nausea/vomiting ( P < .040 ) symptoms were significantly relieved after the program . Conclusion A tailored rehabilitation exercise program provided through a comprehensive mobile health care application was effective in improving patients ' physical capacity and treatment‐related symptoms even during active chemotherapy . Micro‐ Abstract The use of mobile health care applications is a method increasing in use in the cancer care continuum from cancer prevention to cancer diagnosis , cancer treatment , and cancer survivorship . However , no clinical study has yet investigated the effects and feasibility of a smartphone application‐based personalized exercise intervention for colorectal cancer patients undergoing chemotherapy . In 75 colorectal cancer patients undergoing active chemotherapy , a rehabilitation program using a mobile health care application on a wearable device was effective in improving physical function and relieving cancer‐ and cancer treatment‐related toxicities , regardless of the chemotherapy duration Background Cancer survivors have to deal with a wide range of physical symptoms , psychological , social and existential concerns , and lifestyle issues related to cancer and its treatment . Therefore , it is essential that they have access to optimal supportive care services . The eHealth self-management application Oncokompas was developed to support cancer survivors with where they need to turn to for advice and guidance , as well as to increase their knowledge on the availability of optimal support . A r and omised controlled trial will be conducted to assess the efficacy , cost-utility and reach of Oncokompas as an eHealth self-management application compared with care as usual among cancer survivors . Methods / design Adult cancer survivors diagnosed with breast , colorectal or head and neck cancer or lymphoma who are at 3 months to 5 years since curative treatment will be included . In total , 544 cancer survivors will be r and omly assigned to the intervention group or a wait-list control group . The primary outcome measure is patient activation . Secondary outcome measures include self-efficacy , personal control , perceived patient-physician interaction , need for supportive care , mental adjustment to cancer and health-related quality of life . Furthermore , cost-utility outcomes will be assessed . Reach is defined as the percentage of cancer survivors who get access to Oncokompas within the context of this trial . Question naires will be administered at baseline , post-intervention and at 3- and 6-month follow-up . Discussion In this study , we will evaluate the efficacy and cost-utility of Oncokompas among cancer survivors , as well as the reach of Oncokompas . These are essential first steps in the translation of research into practice and contribute to sustainable adoption , implementation and maintenance of an evidence -based Oncokompas . Trial registration Netherl and s Trial Register identifier : NTR5774 . Registered on 8 March 2016 Background Cancer and cancer treatment coincide with substantial negative physical , psychological and psychosocial problems . Physical activity ( PA ) can positively affect the negative effects of cancer and cancer treatment and thereby increase quality of life in CPS . Nevertheless , only a minority of CPS meet PA guidelines . We developed the OncoActive ( OncoActief in Dutch ) intervention : a computer-tailored PA program to stimulate PA in prostate and colorectal CPS , because to our knowledge there are only a few PA interventions for these specific cancer types in the Netherl and s Methods The OncoActive intervention was developed through systematic adaptation of a proven effective , evidence -based , computer-tailored PA intervention for adults over fifty , called Active Plus . The Intervention Mapping ( IM ) protocol was used to guide the systematic adaptation . A literature study and interviews with prostate and colorectal CPS and health care professionals revealed that both general and cancer-specific PA determinants are important and should be addressed . Change objectives , theoretical methods and applications and the actual program content were adapted to address the specific needs , beliefs and cancer-related issues of prostate and colorectal CPS . Intervention participants received tailored PA advice three times , on internet and with printed material s , and a pedometer to set goals to improve PA . Pre- and pilot tests showed that the intervention was highly appreciated ( target group ) and regarded safe and feasible ( healthcare professionals ) . The effectiveness of the intervention is being evaluated in a r and omized controlled trial ( RCT ) ( n = 428 ) , consisting of an intervention group and a usual care waiting-list control group , with follow-up measurements at three , six and twelve months . Participants are recruited from seventeen hospitals and with posters , flyers and calls in several media . Discussion Using the Intervention Mapping protocol result ed in a systematic ally adapted , theory and evidence -based intervention providing tailored PA advice to prostate and colorectal CPS . If the intervention turns out to be effective in increasing PA , as evaluated in a RCT , possibilities for nationwide implementation and extension to other cancer types will be explored . Trial registration The study is registered in the Dutch Trial Register ( NTR4296 ) on November 23rd 2013 and can be accessed at http://www.trialregister.nl/trialreg/admin/ rct view.asp?TC=4296 Background / Objective : Colorectal and gynecologic cancer survivors are at cardiovascular risk due to comorbidities and sedentary behaviour , warranting a feasible intervention to increase physical activity . The Health Action Process Approach ( HAPA ) is a promising theoretical framework for health behaviour change , and wearable physical activity trackers offer a novel means of self-monitoring physical activity for cancer survivors . Method : Sixty-eight survivors of colorectal and gynecologic cancer will be r and omised into 12-week intervention and control groups . Intervention group participants will receive : a Fitbit Alta ™ to monitor physical activity , HAPA-based group sessions , booklet , and support phone-call . Participants in the control group will only receive the HAPA-based booklet . Physical activity ( using accelerometers ) , blood pressure , BMI , and HAPA constructs will be assessed at baseline , 12-weeks ( post-intervention ) and 24-weeks ( follow-up ) . Data analysis will use the Group x Time interaction from a General Linear Mixed Model analysis . Conclusions : Physical activity interventions that are acceptable and have robust theoretical underpinnings show promise for improving the health of cancer survivors Purpose This r and omized controlled trial evaluated the impact of SurvivorCHESS , an eHealth intervention , on physical activity in colon cancer survivors and to explore the impact of SurvivorCHESS on quality of life and distress . Methods This was a two-arm single-blinded multi-site r and omized controlled trial comparing a control group to an intervention group receiving a smartphone with the SurvivorCHESS program . Results Participants using SurvivorCHESS ( n = 144 ) increased their moderate to vigorous physical activities from 19.4 min at baseline to 50 min compared to the control group ( n = 140 ) increasing from 15.5 to 40.3 min at 6 months ( p = .083 ) but was not sustained 3 months after the study ended . No significant differences were found between groups over time for quality of life or distress items . Reports of physical symptoms were greater than other categories for distress items . Patients who had a higher body mass index and number of comorbid conditions were less likely to increase their physical activity . Self-determination theory including autonomous motivation and relatedness was not associated with the outcomes . Conclusions Physical activity did increase over time in both groups and was not significantly different with the use of the eHealth intervention , SurvivorCHESS , compared to the control group . The amount of SurvivorCHESS use was not associated with physical activity . Implication s for cancer survivorsIncreasing physical activity in colon cancer survivors has the potential to improve quality of life and reduce recurrences . Using smartphone-tracking devices may be useful in helping to change this health behavior Introduction While some evidence exists that real-time remote symptom monitoring devices can decrease morbidity and prevent unplanned admissions in oncology patients , overall , these studies have significant method ological weaknesses . The electronic Symptom Management using the Advanced Symptom Management System ( ASyMS ) Remote Technology ( eSMART ) study is design ed to specifically address these weaknesses with an appropriately powered , repeated- measures , parallel-group stratified r and omised controlled trial of oncology patients . Methods and analysis A total of 1108 patients scheduled to commence first-line chemotherapy ( CTX ) for breast , colorectal or haematological cancer will be recruited from multiple sites across five European countries . Patients will be r and omised ( 1:1 ) to the ASyMS intervention ( intervention group ) or to st and ard care currently available at each site ( control group ) . Patients in the control and intervention groups will complete a demographic and clinical question naire , as well as a set of valid and reliable electronic patient-reported outcome measures at enrolment , after each of their CTX cycles ( up to a maximum of six cycles ) and at 3 , 6 , 9 and 12 months after completion of their sixth cycle of CTX . Outcomes that will be assessed include symptom burden ( primary outcome ) , quality of life , supportive care needs , anxiety , self-care self-efficacy , work limitations and cost effectiveness and , from a health professional perspective , changes in clinical practice ( secondary outcomes ) . Ethics and dissemination Ethical approval will be obtained prior to the implementation of all major study amendments . Applications will be su bmi tted to all of the ethics committees that granted initial approval . eSMART received approval from the relevant ethics committees at all of the clinical sites across the five participating countries . In collaboration with the European Cancer Patient Coalition ( ECPC ) , the trial results will be disseminated through publications in scientific journals , presentations at international conferences , and postings on Output:	eHealth could provide useful services for supporting colorectal cancer survivors .
MS2716	*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 Perioperative goal -directed therapy ( PGDT ) may improve postoperative outcome in high-risk surgery patients but its adoption has been slow . In 2012 , we initiated a performance improvement ( PI ) project focusing on the implementation of PGDT during high-risk abdominal surgeries . The objective of the present study was to evaluate the effectiveness of this intervention . Methods This is a historical prospect i ve quality improvement study . The goal of this initiative was to st and ardize the way fluid management and hemodynamic optimization are conducted during high-risk abdominal surgery in the Departments of Anesthesiology and Surgery at the University of California Irvine . For fluid management , the protocol consisted in st and ardized baseline crystalloid administration of 3 ml/kg/hour and any additional boluses based on PGDT . The impact of the intervention was assessed on the length of stay in the hospital ( LOS ) and post-operative complications ( NSQIP data base ) . Results In the 1 year pre- and post-implementation periods , 128 and 202 patients were included . The average volume of fluid administered during the case was 9.9 ( 7.1–13.0 ) ml/kg/hour in the pre-implementation period and 6.6 ( 4.7–9.5 ) ml/kg/hour in the post-implementation period ( p < 0.01 ) . LOS decreased from 10 ( 6–16 ) days to 7 ( 5–11 ) days ( p = 0.0001 ) . Based on the multiple linear regression analysis , the estimated coefficient for intervention was 0.203 ( SE = 0.054 , p = 0.0002 ) indicating that , with the other conditions being held the same , introducing intervention reduced LOS by 18 % ( 95 % confidence interval 9–27 % ) . The incidence of NSQIP complications decreased from 39 % to 25 % ( p = 0.04 ) . Conclusion These results suggest that the implementation of a PI program focusing on the implementation of PGDT can transform fluid administration patterns and improve postoperative outcome in patients undergoing high-risk abdominal surgeries . Trial registration Clinical trials.gov NCT02057653 . Registered 17 December 2013 Introduction Several studies have shown that goal -directed hemodynamic and fluid optimization may result in improved outcome . However , the methods used were either invasive or had other limitations . The aim of this study was to perform intraoperative goal -directed therapy with a minimally invasive , easy to use device ( FloTrac/Vigileo ) , and to evaluate possible improvements in patient outcome determined by the duration of hospital stay and the incidence of complications compared to a st and ard management protocol . Methods In this r and omized , controlled trial 60 high-risk patients scheduled for major abdominal surgery were included . Patients were allocated into either an enhanced hemodynamic monitoring group using a cardiac index based intraoperative optimization protocol ( FloTrac/Vigileo device , GDT-group , n = 30 ) or a st and ard management group ( Control-group , n = 30 ) , based on st and ard monitoring data . Results The median duration of hospital stay was significantly reduced in the GDT-group with 15 ( 12 - 17.75 ) days versus 19 ( 14 - 23.5 ) days ( P = 0.006 ) and fewer patients developed complications than in the Control-group [ 6 patients ( 20 % ) versus 15 patients ( 50 % ) , P = 0.03 ] . The total number of complications was reduced in the GDT-group ( 17 versus 49 complications , P = 0.001 ) . Conclusions In high-risk patients undergoing major abdominal surgery , implementation of an intraoperative goal -directed hemodynamic optimization protocol using the FloTrac/Vigileo device was associated with a reduced length of hospital stay and a lower incidence of complications compared to a st and ard management protocol .Trial Registration Clinical trial registration information : Unique identifier : BACKGROUND In a single-center study published more than a decade ago involving patients presenting to the emergency department with severe sepsis and septic shock , mortality was markedly lower among those who were treated according to a 6-hour protocol of early goal -directed therapy ( EGDT ) , in which intravenous fluids , vasopressors , inotropes , and blood transfusions were adjusted to reach central hemodynamic targets , than among those receiving usual care . We conducted a trial to determine whether these findings were generalizable and whether all aspects of the protocol were necessary . METHODS In 31 emergency departments in the United States , we r and omly assigned patients with septic shock to one of three groups for 6 hours of resuscitation : protocol -based EGDT ; protocol -based st and ard therapy that did not require the placement of a central venous catheter , administration of inotropes , or blood transfusions ; or usual care . The primary end point was 60-day in-hospital mortality . We tested sequentially whether protocol -based care ( EGDT and st and ard-therapy groups combined ) was superior to usual care and whether protocol -based EGDT was superior to protocol -based st and ard therapy . Secondary outcomes included longer-term mortality and the need for organ support . RESULTS We enrolled 1341 patients , of whom 439 were r and omly assigned to protocol -based EGDT , 446 to protocol -based st and ard therapy , and 456 to usual care . Resuscitation strategies differed significantly with respect to the monitoring of central venous pressure and oxygen and the use of intravenous fluids , vasopressors , inotropes , and blood transfusions . By 60 days , there were 92 deaths in the protocol -based EGDT group ( 21.0 % ) , 81 in the protocol -based st and ard-therapy group ( 18.2 % ) , and 86 in the usual-care group ( 18.9 % ) ( relative risk with protocol -based therapy vs. usual care , 1.04 ; 95 % confidence interval [ CI ] , 0.82 to 1.31 ; P=0.83 ; relative risk with protocol -based EGDT vs. protocol -based st and ard therapy , 1.15 ; 95 % CI , 0.88 to 1.51 ; P=0.31 ) . There were no significant differences in 90-day mortality , 1-year mortality , or the need for organ support . CONCLUSIONS In a multicenter trial conducted in the tertiary care setting , protocol -based resuscitation of patients in whom septic shock was diagnosed in the emergency department did not improve outcomes . ( Funded by the National Institute of General Medical Sciences ; ProCESS Clinical Trials.gov number , NCT00510835 . ) BACKGROUND Patients with proximal femoral fracture ( PFF ) are at high risk of postoperative complications . Goal -directed haemodynamic treatment ( GDHT ) in other high-risk surgical patients reduces postoperative complications . We aim ed to compare effects of GDHT and routine fluid treatment ( RFT ) on postoperative outcomes after PFF surgery . METHODS PFF patients ( ≥70 yr ) were enrolled in this single-centre , open , r and omized , controlled , parallel-group superiority trial with concealed allocation using computer-generated r and omization . TREATMENTS ( i ) GDHT to attain oxygen delivery index > 600 ml min(-1 ) m(-2 ) using fluids and dobutamine and ( ii ) a protocol -guided RFT . After 150 enrolled patients , the trial was stopped due to slow recruitment . The short-term primary outcome measure was the relative risk ( RR ) of postoperative complications ; secondary measures were ( i ) administered fluid levels , ( ii ) vasopressor requirements , and ( iii ) haemodynamic responses . RESULTS For the GDHT group , 74 and for the RFT group 75 patients were design ated . The RR of postoperative complications ( GDHT vs RFT ) was 0.79 ( 95 % confidence interval 0.54 - 1.16 ) ; the volumes of i.v . fluids decreased ( 1078 vs 1440 ml , P=0.01 ) ; fewer patients required treatment of hypotension ( 18.5 % vs 75 % , P<0.005 ) ; there were more patients with increased oxygen delivery at the end of operation ( 28 % vs 8 % , P=0.04 ) , but the haemodynamic goal was achieved in only 27 % of patients in the GDHT group . CONCLUSIONS The magnitude of risk reduction of postoperative complications is clinical ly relevant , but the trial was underpowered and the null hypothesis can not be rejected Background Our aim was to determine whether substitution of goal -directed fluid therapy ( GDT ) ( perioperative fluid administration ) for traditional therapy to manage elderly patients with coronary heart disease scheduled for gastrointestinal ( GI ) surgery was advantageous . We determined if it would reduce cardiac complications and shorten time to recovery and discharge . Methods Altogether , 60 of these elderly patients were r and omized into GDT ( n = 30 ) and control ( n = 30 ) groups . In the GDT group , fluid management was carried out under guidance of hemodynamic status indicators . Types and quantities of fluids administered , blood loss , intraoperative urine output , time of extubation , intensive care unit ( ICU ) stay , hospital stay , postoperative adverse cardiac events , and GI complications were recorded . Results Total fluids infused were 2,910 ± 645 ml ( GDT group ) and 3,640 ± 771 ml ( control group ) ( p < 0.05 ) . Numbers of adverse cardiac events in the two groups were not significantly different ( p = 0.121 ) . Return of GI function was significantly faster in the GDT group ( p < 0.001 ) . Median ICU stay was 32.5 h in the GDT group and 47.5 h in the control group ( p < 0.001 ) . Median hospital stay was 18 days in the GDT group and 22 days in the control group ( p < 0.001 ) . Conclusions GDT was associated with shorter ICU stay and time to discharge and faster return of GI function compared to traditional fluid therapy . The number of adverse cardiac events was similar in the two groups Introduction Total hip replacement is one of the most commonly performed major orthopaedic operations . Goal -directed therapy ( GDT ) using haemodynamic monitoring has previously demonstrated outcome benefits in high-risk surgical patients under general anaesthesia . GDT has never been formally assessed during regional anaesthesia . Methods Patients undergoing total hip replacement while under regional anaesthesia were r and omised to either the control group ( CTRL ) or the protocol group ( GDT ) . Patients in the GDT group , in addition to st and ard monitoring , were connected to the FloTrac sensor/Vigileo monitor haemodynamic monitoring system , and a GDT protocol was used to maximise the stroke volume and target the oxygen delivery index to > 600 mL/minute/m2 . Results Patients r and omised to the GDT group were given a greater volume of intravenous fluids during the intraoperative period ( means ± st and ard deviation ( SD ) : 6,032 ± 1,388 mL vs. 2,635 ± 346 mL ; P < 0.0001 ) , and more of the GDT patients received dobutamine ( 0 of 20 CTRL patients vs. 11 of 20 GDT patients ; P < 0.0003 ) . The GDT patients also received more blood transfused during the intraoperative period ( means ± SD : 595 ± 316 mL vs. 0 ± 0 mL ; P < 0.0001 ) , although the CTRL group received greater volumes of blood replacement postoperatively ( CTRL patients 658 ± 68 mL vs. GDT patients 198 ± 292 mL ; P < 0.001 ) . Overall blood consumption ( intraoperatively and postoperatively ) was not different between the two groups . There were an increased number of complications in the CTRL group ( 20 of 20 CTRL patients ( 100 % ) vs. 16 of 20 GDT patients ( 80 % ) ; P = 0.05 ) . These outcomes were predominantly due to a difference in minor complications ( 20 of 20 CTRL patients ( 100 % ) vs. 15 of 20 GDT patients ( 75 % ) ; P = 0.047 ) . Conclusions GDT applied during regional anaesthesia in patients undergoing elective total hip replacement changes intraoperative fluid management and may improve patient outcomes by decreasing postoperative complications . Larger trials are required to confirm our findings .Trial registration S RCT Organ dysfunction and multiple organ failure are the main causes of prolonged hospital stay after cardiac surgery , which increases re source use and health care costs . Increased levels of oxygen delivery and consumption are associated with improved outcome in different groups of postoperative patients . Cardiac surgical patients are at risk of inadequate perioperative oxygen delivery caused by extracorporeal circulation and limited cardiovascular reserves . The purpose of our study was to test whether increasing oxygen delivery immediately after cardiac surgery would shorten hospital and intensive care unit ( ICU ) stay . Four hundred three elective cardiac surgical patients were enrolled in the study and r and omly assigned to either the control or the protocol group . Goals of the protocol group were to maintain Svo2 > 70 % and lactate concentration ≤2.0 mmol/L from admission to the ICU and up to 8 h thereafter . Hemodynamics , oxygen transport data , and organ dysfunctions were recorded Output:	Conclusions The principal finding of this meta- analysis is that after adjusting for confounders , there is insufficient evidence to associate targeting urine output with an effect on 30-day mortality .
MS2717	*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 Whether remote ischemic preconditioning ( transient ischemia and reperfusion of the arm ) can improve clinical outcomes in patients undergoing coronary-artery bypass graft ( CABG ) surgery is not known . We investigated this question in a r and omized trial . METHODS We conducted a multicenter , sham-controlled trial involving adults at increased surgical risk who were undergoing on-pump CABG ( with or without valve surgery ) with blood cardioplegia . After anesthesia induction and before surgical incision , patients were r and omly assigned to remote ischemic preconditioning ( four 5-minute inflations and deflations of a st and ard blood-pressure cuff on the upper arm ) or sham conditioning ( control group ) . Anesthetic management and perioperative care were not st and ardized . The combined primary end point was death from cardiovascular causes , nonfatal myocardial infa rct ion , coronary revascularization , or stroke , assessed 12 months after r and omization . RESULTS We enrolled a total of 1612 patients ( 811 in the control group and 801 in the ischemic-preconditioning group ) at 30 cardiac surgery centers in the United Kingdom . There was no significant difference in the cumulative incidence of the primary end point at 12 months between the patients in the remote ischemic preconditioning group and those in the control group ( 212 patients [ 26.5 % ] and 225 patients [ 27.7 % ] , respectively ; hazard ratio with ischemic preconditioning , 0.95 ; 95 % confidence interval , 0.79 to 1.15 ; P=0.58 ) . Furthermore , there were no significant between-group differences in either adverse events or the secondary end points of perioperative myocardial injury ( assessed on the basis of the area under the curve for the high-sensitivity assay of serum troponin T at 72 hours ) , inotrope score ( calculated from the maximum dose of the individual inotropic agents administered in the first 3 days after surgery ) , acute kidney injury , duration of stay in the intensive care unit and hospital , distance on the 6-minute walk test , and quality of life . CONCLUSIONS Remote ischemic preconditioning did not improve clinical outcomes in patients undergoing elective on-pump CABG with or without valve surgery . ( Funded by the Efficacy and Mechanism Evaluation Program [ a Medical Research Council and National Institute of Health Research partnership ] and the British Heart Foundation ; ERICCA Clinical Trials.gov number , NCT01247545 . ) Background : Two preconditioning stimuli should induce a more consistent overall cell protection . We hypothesized that remote ischemic preconditioning ( RIPC , second preconditioning stimulus ) applied during isoflurane inhalation ( first preconditioning stimulus ) would provide more protection to the myocardium of patients undergoing on-pump coronary artery bypass grafting . Methods : In this placebo-controlled r and omized controlled study , patients in the RIPC group received four 5-min cycles of 300 mmHg cuff inflation/deflation of the leg before aortic cross-clamping . Anesthesia consisted of opioids and propofol for induction and isoflurane for maintenance . The primary outcome was high-sensitivity cardiac troponin T release . Secondary endpoints were plasma levels of N-terminal pro-brain natriuretic peptide , high-sensitivity C-reactive protein , S100 protein , and short- and long-term clinical outcomes . Gene expression profiles were obtained from atrial tissue using microarrays . Results : RIPC ( n = 27 ) did not reduce high-sensitivity cardiac troponin T release when compared with placebo ( n = 28 ) . Likewise , N-terminal pro-brain natriuretic peptide , a marker of myocardial dysfunction ; high-sensitivity C-reactive protein , a marker of perioperative inflammatory response ; and S100 , a marker of cerebral injury , were not different between the groups . The incidence for the perioperative composite endpoint combining new arrhythmias and myocardial infa rct ions was higher in the RIPC group than the placebo group ( 14/27 vs. 6/28 , P = 0.036 ) . However , there was no difference in the 6-month cardiovascular outcome . N-terminal pro-brain natriuretic peptide release correlated with isoflurane-induced transcriptional changes in fatty-acid metabolism ( P = 0.001 ) and DNA-damage signaling ( P < 0.001 ) , but not with RIPC-induced changes in gene expression . Conclusions : RIPC applied during isoflurane inhalation provides no benefit to the myocardium of patients undergoing on-pump coronary artery bypass grafting BACKGROUND Remote ischemic preconditioning ( RIPC ) is reported to reduce biomarkers of ischemic and reperfusion injury in patients undergoing cardiac surgery , but uncertainty about clinical outcomes remains . METHODS We conducted a prospect i ve , double-blind , multicenter , r and omized , controlled trial involving adults who were scheduled for elective cardiac surgery requiring cardiopulmonary bypass under total anesthesia with intravenous propofol . The trial compared upper-limb RIPC with a sham intervention . The primary end point was a composite of death , myocardial infa rct ion , stroke , or acute renal failure up to the time of hospital discharge . Secondary end points included the occurrence of any individual component of the primary end point by day 90 . RESULTS A total of 1403 patients underwent r and omization . The full analysis set comprised 1385 patients ( 692 in the RIPC group and 693 in the sham-RIPC group ) . There was no significant between-group difference in the rate of the composite primary end point ( 99 patients [ 14.3 % ] in the RIPC group and 101 [ 14.6 % ] in the sham-RIPC group , P=0.89 ) or of any of the individual components : death ( 9 patients [ 1.3 % ] and 4 [ 0.6 % ] , respectively ; P=0.21 ) , myocardial infa rct ion ( 47 [ 6.8 % ] and 63 [ 9.1 % ] , P=0.12 ) , stroke ( 14 [ 2.0 % ] and 15 [ 2.2 % ] , P=0.79 ) , and acute renal failure ( 42 [ 6.1 % ] and 35 [ 5.1 % ] , P=0.45 ) . The results were similar in the per- protocol analysis . No treatment effect was found in any subgroup analysis . No significant differences between the RIPC group and the sham-RIPC group were seen in the level of troponin release , the duration of mechanical ventilation , the length of stay in the intensive care unit or the hospital , new onset of atrial fibrillation , and the incidence of postoperative delirium . No RIPC-related adverse events were observed . CONCLUSIONS Upper-limb RIPC performed while patients were under propofol-induced anesthesia did not show a relevant benefit among patients undergoing elective cardiac surgery . ( Funded by the German Research Foundation ; RIPHeart Clinical Trials.gov number , NCT01067703 . ) BACKGROUND Although remote ischemic preconditioning ( RIPC ) has emerged as an attractive strategy to reduce cardiac injury in patients undergoing diverse cardiac surgical procedures , it is unclear whether RIPC has protective effects in patients undergoing aortic valve replacement surgery without coronary artery bypass grafting ( CABG ) . METHODS Hence , 100 adult patients undergoing elective aortic valve replacement for aortic valve stenosis , without combined surgery with CABG , were prospect ively r and omly assigned in a 1:1 ratio to either the RIPC group or the control group . The RIPC group underwent three cycles of 5-min inflation to 200mmHg and 5-min deflation of an automated upper-arm cuff inflator after induction of anesthesia . The control group had a deflated cuff placed on upper arm for 30min . The primary endpoint was 72-h area under curve ( AUC ) for troponin I ( cTnI ) . Secondary endpoints were 72-h AUC for creatine kinase-MB isoenzyme ( CK-MB ) release , incidence of acute kidney injury , extubation time , length of stay in intensive care unit , and simplified acute physiology score ( SAPS II ) . RESULTS There were no significant differences in cTnI AUC [ 195±190 arbitrary units ( a.u . ) in RIPC group vs. 169±117 a.u . in the control group ; p=0.41 ] and CK-MB AUC between groups . None of the other secondary endpoints differed between groups . Acute kidney injury occurred in 12 patients ( 24.5 % ) in the control group and in 13 ( 26.0 % ) in the RIPC group ( p=0.86 ) . CONCLUSIONS RIPC did not exhibit significant cardiac or kidney protective effects in patients undergoing aortic valve replacement surgery without CABG Background Remote ischemic preconditioning ( RIPC ) has been shown to enhance the tolerance of remote organs to cope with a subsequent ischemic event . We hypothesized that RIPC reduces postoperative neurocognitive dysfunction ( POCD ) in patients undergoing complex cardiac surgery . Methods We conducted a prospect i ve , r and omized , double-blind , controlled trial including 180 adult patients undergoing elective cardiac surgery with cardiopulmonary bypass . Patients were r and omized either to RIPC or to control group . Primary endpoint was postoperative neurocognitive dysfunction 5–7 days after surgery assessed by a comprehensive test battery . Cognitive change was assumed if the preoperative to postoperative difference in 2 or more tasks assessing different cognitive domains exceeded more than one SD ( 1 SD criterion ) or if the combined Z score was 1.96 or greater ( Z score criterion ) . Results According to 1 SD criterion , 52 % of control and 46 % of RIPC patients had cognitive deterioration 5–7 days after surgery ( p = 0.753 ) . The summarized Z score showed a trend to more cognitive decline in the control group ( 2.16±5.30 ) compared to the RIPC group ( 1.14±4.02 ; p = 0.228 ) . Three months after surgery , incidence and severity of neurocognitive dysfunction did not differ between control and RIPC . RIPC tended to decrease postoperative troponin T release at both 12 hours [ 0.60 ( 0.19–1.94 ) µg/L vs. 0.48 ( 0.07–1.84 ) µg/L ] and 24 hours after surgery [ 0.36 ( 0.14–1.89 ) µg/L vs. 0.26 ( 0.07–0.90 ) µg/L ] . Conclusions We failed to demonstrate efficacy of a RIPC protocol with respect to incidence and severity of POCD and secondary outcome variables in patients undergoing a wide range of cardiac surgery . Therefore , definitive large-scale multicenter trials are needed . Trial Registration Clinical Trials.gov Acute kidney injury ( AKI ) is a frequent complication of cardiac surgery and usually occurs in patients with preexisting chronic kidney disease ( CKD ) . Remote ischemic preconditioning ( RIPC ) may mitigate the renal ischemia-reperfusion injury associated with cardiac surgery and may be a preventive strategy for postsurgical AKI . We undertook a r and omized controlled trial of RIPC to prevent AKI in 86 patients with CKD ( estimated glomerular filtration rate under 60 ml/min per 1.73 m(2 ) ) undergoing coronary artery bypass graft ( CABG ) surgery . Forty-three patients each were r and omized to receive st and ard care with or without RIPC consisting of three 5-minute cycles of forearm ischemia followed by reperfusion . The primary end point was the development of AKI defined as an increase in serum creatinine concentration over 0.3 mg/dl within 48 h of surgery . Secondary end points included a comparison between the study and control groups of several serum biomarkers of renal injury including cystatin-C , neutrophil gelatinase-associated lipocalin ( NGAL ) , and interleukin-18 ( IL-18 ) , and urinary biomarkers including NGAL , IL-18 , and kidney injury molecule-1 measured at 6 , 12 , and 24 h after CABG , and the 72-h serum troponin T concentration area under the curve as a marker of myocardial injury . Clinical and operative characteristics were similar between the preconditioned and control groups . AKI developed in 12 patients in both groups within 48 h of CABG . There were no significant differences between the two groups in the concentrations of any of the serum or urinary biomarkers of renal or cardiac injury after CABG . Thus , RIPC induced by forearm ischemia-reperfusion had no effect on the frequency of AKI after CABG in patients with CKD Background : Remote ischemic preconditioning is a simple therapy that may reduce cardiac and kidney injury . We undertook a r and omized controlled trial to evaluate the effect of this ther Output:	Conversely , except for MIBs , RIPC had fewer non-significant effects under propofol with or without volatile anaesthetics . Conclusions RIPC did not consistently reduce morbidity and mortality in adults undergoing cardiac surgery with CPB . In the subgroup on volatile anaesthetics only , RIPC markedly and significantly reduced the incidence of AKI and composite endpoint as well as myocardial injury
MS2718	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: In a double-blind study on 19 patients with the diagnosis of chronic pancreatitis , the effects of treatment with a granulated pancreatic enzyme preparation ( Pankreon ) were compared with those of placebo administration . One week of treatment with each preparation was preceded by one week without any medication . The patients kept daidy records of their symptoms , plotting the severity of pain on an analog scale . Weekly assessment s of the mean pain level were also made by an examiner question ing the patients . Recordings of body weights and pancreas and liver laboratory tests were done weekly . Fifteen of 19 patients noted less pain during the week of treatment with pancreatic enzymes as compared to that of placebo treatment ( P<0.05 ) . The average reduction of pain , as calculated for all patients , was 30 % as evaluated by both patients ( P<0.01 ) and the examiner ( P<0.05 ) . No differences were found in other parameters examined . A possible explanation of the findings could be an effect on the intraductal pressure by intraluminal trypsin BACKGROUND This study was aim ed to investigate the effect of long-term treatment with high-protease pancreatic extract on the recurrent abdominal pain of patients with chronic pancreatitis . METHODS Twenty-six patients with a firm diagnosis of chronic pancreatitis and a pattern of recurrent pain were recruited and r and omly assigned to treatment with pancreatic extract ( Pancrex-Duo capsules , each containing 34,375 USP units of protease in enteric-coated microspheres ) or placebo , at a dose of four capsules four times daily , for 4 months . At the end of the first period patients were switched to the other medication for the next 4 months . Four patients did not complete the study because of unbearable recurring pain or inadequate compliance with treatment . The other 22 patients daily recorded the presence , intensity , and duration of pain and the consumption of analgesics , for 8 months . RESULTS No difference was found when intraindividual records during placebo and extract treatment periods were compared . Conversely , in the second 4 months of follow-up , regardless of the treatment given in the first period , there was a significant reduction in the cumulative pain score ( median , 95 ; range , 0 - 1005 , versus 134 ; 0 - 972 ; p < 0.05 ) , in the number of days ( 8 ; 0 - 132 , versus 13 ; 0 - 126 ; p < 0.02 ) and hours ( 54 ; 0 - 680 , versus 80 ; 0 - 602 ; p < 0.05 ) of pain , and in the analgesic consumption score ( 0 ; 0 - 22 , versus 12 ; 0 - 44 ; p = 0.02 ) . CONCLUSIONS Chronic supplementation with pancreatic extract is not beneficial in the management of recurrent pain in patients with chronic pancreatitis Background Chronic pancreatitis often culminates in maldigestion and diabetes . Clinical management is complex as the correction of maldigestion often disturbs diabetic control . Study In the following study , we examined the effects of a potent new commercial pancreatic enzyme on food absorption and blood glucose control . Enzymes were manufactured in enteric-coated mini-microsphere form ( 0.7–1.6 mm ) , design ed to prevent gastric acid degradation and facilitate co-migration with food , and given in quantities calculated to cover normal digestion requirements ( four capsules with meals , two with snacks ; content/capsule : lipase 10,000 USP units , protease 37,500 units , amylase 33,200 units ) . Forty patients with chronic pancreatitis were screened during a run-in nonenzyme-supplemented phase ; only those with stool fat excretion rates over 10 g/d ( n = 29 ) were advanced to a 14-day parallel r and omized placebo versus enzyme supplement group comparison . Results Of these , 62 % were diabetic ( 50 % insulin-dependent ) and 52 % were malnourished ( body mass index less than 20 kg/m2 ) . After enzyme supplementation , stool fat and nitrogen excretion decreased , whereas fat absorption increased from 54.0 ± 9.7 % to 80.8 ± 3.8 % per day ( p = 0.002 ) and protein from 80.5 ± 3.4 % to 86.8 ± 2.2 % per day ( p = 0.004 ) . Changing treatment from active enzyme supplementation to placebo ( and vice versa ) result ed in major problems with glucose control ; blood glucose levels became abnormal in 28 of 29 patients , one patient required hospitalization for symptomatic hypoglycemia ( 0.9 mmol/L ) during placebo treatment , and one developed diabetic ketoacidosis after recommencing active enzyme supplementation . Conclusions In conclusion , high-dose pancreatin mini-microspheres improved , but did not normalize , fat absorption , possibly because of the residual influence of diabetes and malnutrition on absorptive function . In view of the brittle nature of blood glucose control in malnourished insulin-dependent patients , enzyme adjustment should be carefully supervised in-hospital According to the theory of negative feedback regulation of pancreatic enzyme secretion by proteases , treatment with pancreatic extracts has been proposed to lower pain in chronic pancreatitis by decreasing pancreatic duct pressure . We conducted a prospect i ve placebo-controlled double blind multicenter study to investigate the effect of porcine pancreatic extracts on pain in chronic pancreatitis . 47 patients with pain ( 41 males , 6 females ) due to chronic pancreatitis documented by sonography , endoscopic retro grade cholangiopancreatography , and CT were included . Exclusion criteria were steatorrhea above 30 g/day , gastric or pancreatic resections in the history , and serum bilirubin above 1.5 mg/dl . Patients received pancreatic extracts ( acid-protected microtablets ; Panzytrat -20,000 ; 5 x 2 capsules/day ; proteases/capsule 1,000 Pharmacopoea europaea units ) for 14 days followed by treatment with placebo for another 14 days or vice versa . Pain ( grade d from 0 to 3 ) and concomitant use of analgesics ( N-butylscopolaminiumbromide and tramadol ) were recorded by diary . Physical examination and blood chemistry were done at day -1 , 15 and 29 . Quantitative stool fat was determined at days -2/-1 , 13/14 and 27/28 . 43 patients completed the studies . Pain improved in most patients irrespective of whether they started with placebo or verum . There was no significant difference between both treatment arms . We conclude that pancreatic extracts are not very efficient in lowering pain The symptomatic effect of pancreatic enzyme substitution therapy was examined in a 4-week double-blind crossover study . Twenty patients , 11 with and 9 without steatorrhoea , were examined . Pancreatic steatorrhoea was reduced from a median of 24 g/day to 10 g/day by the enzyme therapy ( P less than 0.01 ) . No significant pain reduction was found in either of the two groups , although there was a tendency to reduction in pain and analgetic consumption in the patients with steatorrhoea when treated with pancreatic enzymes . It is concluded that pancreatic steatorrhoea is still the only indication for pancreatic enzyme therapy Output:	Conclusion .
MS2719	*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 Radiotherapy for early breast cancer can decrease breast cancer mortality but increase other mortality , mainly from heart disease and lung cancer . The mean cardiac dose from irradiation of a left-sided breast cancer can be two or three times that for a right-sided breast cancer . The mean ipsilateral ( ie , on the same side as the breast cancer ) lung dose can also be two or three times the mean contralateral lung dose . Particularly during the 1970s , when typical heart and lung exposures were greater than now , the laterality of an irradiated breast cancer could measurably affect cardiac mortality and mortality from cancer of the right or the left lung decades later . This study aim ed to assess the hazards in the general US population from routine cancer-registry and death-certificate data . METHODS We analysed data for 308 861 US women with early breast cancer of known laterality ( left-sided or right-sided ) who were registered in the US Surveillance Epidemiology and End Results ( SEER ) cancer registries during 1973 - 2001 and followed prospect ively for cause-specific mortality until Jan 1 , 2002 . FINDINGS 115 165 ( 37 % ) received radiotherapy . Among those who did not , tumour laterality was of little relevance to subsequent mortality . For women diagnosed during 1973 - 82 and irradiated , the cardiac mortality ratio ( left versus right tumour laterality ) was 1.20 ( 95 % CI 1.04 - 1.38 ) less than 10 years afterwards , 1.42 ( 1.11 - 1.82 ) 10 - 14 years afterwards , and 1.58 ( 1.29 - 1.95 ) after 15 years or more ( trend : 2p=0.03 ) . For women diagnosed during 1983 - 92 and irradiated , the cardiac mortality ratio was 1.04 ( 0.91 - 1.18 ) less than 10 years afterwards and 1.27 ( 0.99 - 1.63 ) 10 or more years afterwards . For women diagnosed during 1993 - 2001 and irradiated the cardiac mortality ratio was 0.96 ( 0.82 - 1.12 ) , with none yet followed for 10 years . Among women irradiated for breast cancer who subsequently developed an ipsilateral or contralateral lung cancer , the lung cancer mortality ratio ( ipsilateral versus contralateral ) for women diagnosed during 1973 - 82 and irradiated was 1.17 ( 0.62 - 2.19 ) , 2.00 ( 1.00 - 4.00 ) , and 2.71 ( 1.65 - 4.48 ) , respectively , less than 10 years , 10 - 14 years , and 15 or more years afterwards ( trend : 2p=0.04 ) . For women irradiated after 1982 there is , as yet , little information on lung cancer risks more than 10 years afterwards . INTERPRETATION US breast cancer radiotherapy regimens of the 1970s and early 1980s appreciably increased mortality from heart disease and lung cancer 10 - 20 years afterwards with , as yet , little direct evidence on the hazards after more than 20 years . Since the early 1980s , improvements in radiotherapy planning should have reduced such risks , but the long-term hazards in the general population s of various countries still need to be monitored directly PURPOSE To study incidence of radiation-related heart disease in a large population of breast cancer patients followed for up to 30 years . MATERIAL AND METHODS 72,134 women diagnosed with breast cancer in Denmark or Sweden during 1976 - 2006 and followed prospect ively . Radiation-related risk was studied by comparing women with left-sided and right-sided tumours . RESULTS 34,825 women ( 48 % ) received radiotherapy . Among unirradiated women tumour laterality had little relevance to heart disease . Among irradiated women mean dose to the whole heart was 6.3 Gy for left-sided tumours and 2.7 Gy for right-sided tumours . Mortality was similar in irradiated women with left-sided and right-sided tumours , but incidence ratios , left-sided versus right-sided , were raised : acute myocardial infa rct ion 1.22 ( 95 % CI 1.06 - 1.42 ) , angina 1.25 ( 1.05 - 1.49 ) , pericarditis 1.61 ( 1.06 - 2.43 ) , valvular heart disease 1.54 ( 1.11 - 2.13 ) . Incidence ratios for all heart disease were as high for women irradiated since 1990 ( 1.09 [ 1.00 - 1.19 ] ) as for women irradiated during 1976 - 1989 ( 1.08 [ 0.99 - 1.17 ] ) , and were higher for women diagnosed with ischaemic heart disease prior to breast cancer than for other women ( 1.58 [ 1.19 - 2.10 ] versus 1.08 [ 1.01 - 1.15 ] , p for difference=0.01 ) . CONCLUSIONS Breast cancer radiotherapy has , at least until recently , increased the risk of developing ischaemic heart disease , pericarditis and valvular disease . Women with ischaemic heart disease before breast cancer diagnosis may have incurred higher risks than others CONTEXT Heart failure incidence increases with advancing age , and approximately half of patients with heart failure have preserved left ventricular ejection fraction . Although diastolic dysfunction plays a role in heart failure with preserved ejection fraction , little is known about age-dependent longitudinal changes in diastolic function in community population s. OBJECTIVE To measure changes in diastolic function over time and to determine the relationship between diastolic dysfunction and the risk of subsequent heart failure . DESIGN , SETTING , AND PARTICIPANTS Population -based cohort of participants enrolled in the Olmsted County Heart Function Study . R and omly selected participants 45 years or older ( N = 2042 ) underwent clinical evaluation , medical record abstract ion , and echocardiography ( examination 1 [ 1997 - 2000 ] ) . Diastolic left ventricular function was grade d as normal , mild , moderate , or severe by vali date d Doppler techniques . After 4 years , participants were invited to return for examination 2 ( 2001 - 2004 ) . The cohort of participants returning for examination 2 ( n = 1402 of 1960 surviving [ 72 % ] ) then underwent follow-up for ascertainment of new-onset heart failure ( 2004 - 2010 ) . MAIN OUTCOME MEASURES Change in diastolic function grade and incident heart failure . RESULTS During the 4 ( SD , 0.3 ) years between examinations 1 and 2 , diastolic dysfunction prevalence increased from 23.8 % ( 95 % confidence interval [ CI ] , 21.2%-26.4 % ) to 39.2 % ( 95 % CI , 36.3%-42.2 % ) ( P < .001 ) . Diastolic function grade worsened in 23.4 % ( 95 % CI , 20.9%-26.0 % ) of participants , was unchanged in 67.8 % ( 95 % CI , 64.8%-70.6 % ) , and improved in 8.8 % ( 95 % CI , 7.1%-10.5 % ) . Worsened diastolic dysfunction was associated with age 65 years or older ( odds ratio , 2.85 [ 95 % CI , 1.77 - 4.72 ] ) . During 6.3 ( SD , 2.3 ) years of additional follow-up , heart failure occurred in 2.6 % ( 95 % CI , 1.4%-3.8 % ) , 7.8 % ( 95 % CI , 5.8%-13.0 % ) , and 12.2 % ( 95 % CI , 8.5%-18.4 % ) of persons whose diastolic function normalized or remained normal , remained or progressed to mild dysfunction , or remained or progressed to moderate or severe dysfunction , respectively ( P < .001 ) . Diastolic dysfunction was associated with incident heart failure after adjustment for age , hypertension , diabetes , and coronary artery disease ( hazard ratio , 1.81 [ 95 % CI , 1.01 - 3.48 ] ) . CONCLUSIONS In a population -based cohort undergoing 4 years of follow-up , prevalence of diastolic dysfunction increased . Diastolic dysfunction was associated with development of heart failure during 6 years of subsequent follow-up PURPOSE To assess cardiac mortality , coronary artery disease , myocardial dysfunction , and valvular heart disease in women younger than 65 years of age , at least 10 years after adjuvant radiotherapy following mastectomy in early breast cancer . METHODS AND MATERIAL S Ninety women ( 45 - 64 years old ) with Stage II breast cancer without relapse , included in the South Sweden Breast Cancer Trial ( premenopausal arm ) , with or without adjuvant postoperative radiotherapy + /- cyclophosphamide were examined with myocardial scintigraphy and echocardiography/Doppler , 10 - 17 years after radiotherapy . Thirty-four patients had been irradiated for left-sided tumors , 33 for right-sided tumors , and 23 patients had not been treated with radiotherapy . The radiotherapy ( conventional roentgen , electron beams , and high-energy photon beams combined , in each patient ) included the chest wall and the regional lymph nodes , with a specified target dose of 38 - 48 Gy , administered in daily fractions of 1.9 - 2.4 Gy , 5 days/week . RESULTS No cardiac deaths were found among the original 275 patients r and omized to adjuvant therapy . In the 90 patients examined , abnormal findings were recorded for ECG ( 14 patients ) , exercise test ( 5 patients ) , myocardial scintigraphy ( 6 patients ) , thickening of valve cusps ( 14 patients ) , and mild valvular regurgitation ( 20 patients ) . All patients had normal systolic function . Diastolic dysfunction was observed in 6 patients ( abnormal relaxation in 4 patients and restrictive filling abnormality in 2 patients ) . Although no significant differences were found between the 3 study groups , there was a tendency to more abnormal findings after radiotherapy . CONCLUSION Women younger than 50 years of age at the time of adjuvant radiotherapy following mastectomy in early breast cancer , had no serious cardiac sequelae 13 years ( median ) later , despite partly old-fashioned radiation techniques We evaluated the long-term effects of combined modality therapy ( CMT ) with adriamycin , bleomycin , vinblastine , dacarbazine ( ABVD ) or mechlorethamine , vincristine , prednisone , procarbazine (MOPP)/ABVD plus adjuvant low-dose ( < 30 Gy ) involved-field radiation therapy ( LDRT ) on cardiac and pulmonary functions in adult patients with Hodgkin 's disease ( HD ) . Adjuvant LDRT ( mean dose , 2340 cGy ) to the mediastinum was administered to 24 patients after chemotherapy with MOPP/ABVD ( n = 10 ) and ABVD ( n = 14 ) . The mean doses of doxorubicin and bleomycin were 233 mg/m2 and 92 IU/m2 , respectively . Cardiac and pulmonary function tests were performed in all patients and , when available , were compared with pretreatment studies . After a median follow-up of 6.3 years , none of the patients had cardiac or pulmonary symptoms . A 4.7 % overall decrease in left ventricular ejection fraction ( LVEF ) was observed ( p = 0.03 ) , but only one patient had a mildly decreased LVEF ( 47 % ) . Diastolic function , LVEF , and left ventricular volume remained within the normal range in the other 23 patients . Mild pulmonary function study abnormalities occurred in 8 of 24 patients , 6 of whom were cigarette smokers . There were no significant changes in total lung capacity and forced vital capacity ( FVC ) values , but there was a 3 % overall decrease in FEV1/FVC ratio ( p = 0.05 ) . In adult patients with HD , adjuvant LDRT after chemotherapy with ABVD or MOPP/ABVD did not result in a significant incidence of permanent pulmonary or cardiac toxicity after more than 6.3 years of median follow-up . Further studies are warranted to fully evaluate the impact of such therapy on cardiopulmonary function Purpose Whereas earlier research focused on specific patient groups , this study assessed the risk of cardiovascular disease ( CVD ) in an unselected population curatively treated for breast cancer ( BC ) , compared with an age-matched r and om sample of controls . Methods Risks were determined in BC survivors and controls . CVD was divided into three categories : congestive heart failure , vascular cardiac diseases , and “ other ” cardiac Output:	This might have implication s for the selection of patients for cardioprotection . Despite common emphasis , diastolic functional abnormalities were infrequent in the long term . A limited amount of data suggest that right ventricular dysfunction is important in this population .
MS2720	*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 represents a 2.25-year follow-up to a treatment study reported earlier ( McLean & Hakstian , 1979 ) in which 121 unipolar depressed out patients were treated by either ( a ) nondirective psychotherapy , ( b ) behavior therapy , ( c ) pharmacotherapy , or ( d ) relaxation therapy . A nondepressed , normal control group was evaluated on the same 28 measures and 6 intervals for contrast purpose s. Behavior therapy patients alone were significantly improved in the areas of mood , personal productivity , and social activity , relative to treatment control patients over the follow-up period . Also , twice as many behavior therapy patients ( i.e. , 64 % ) fell within one st and ard deviation of the normal , nondepressed control group distribution on depressed mood , compared with non-directive psychotherapy and pharmacotherapy patients , when scores were aggregated across the 6 assessment points Eighty-four depressed pregnant women were recruited during the second trimester of pregnancy and r and omly assigned to a massage therapy group , a progressive muscle relaxation group or a control group that received st and ard prenatal care alone . These groups were compared to each other and to a non-depressed group at the end of pregnancy . The massage therapy group participants received two 20 min therapy sessions by their significant others each week for 16 weeks of pregnancy , starting during the second trimester . The relaxation group provided themselves with progressive muscle relaxation sessions on the same time schedule . Immediately after the massage therapy sessions on the first and last days of the 16-week period the women reported lower levels of anxiety and depressed mood and less leg and back pain . By the end of the study the massage group had higher dopamine and serotonin levels and lower levels of cortisol and norepinephrine . These changes may have contributed to the reduced fetal activity and the better neonatal outcome for the massage group ( i.e. lesser incidence of prematurity and low birthweight ) , as well as their better performance on the Brazelton Neonatal Behavior Assessment . The data suggest that depressed pregnant women and their offspring can benefit from massage therapy Les auteurs ont trouve une efficacite semblable pour la therapie cognitivo-comportementale et pour la relaxation , dans le traitement de la depression chez Outcomes of seven treatment trials comparing cognitive behavioral therapy to treatment with tricyclic antidepressant medication in major depressive disorder have been quite similar to one another . This led us to question whether treatment outcome in time-limited studies reflected a unique effect of cognitive behavioral therapy . To test the uniqueness hypothesis , relaxation training , a nonpharmacologic , noncognitive treatment , was chosen as a comparison for cognitive behavioral therapy as well as drug therapy . Treatment duration was 16 weeks . The sample of 37 patients treated for major depressive disorder was less depressed than those previously studied . For both cognitive behavioral therapy and relaxation training , outcome of depression was superior to that of tricyclic antidepressant medication by endpoint analysis . The posttreatment scores on the Beck Depression Inventory of 82 % of the group receiving cognitive behavioral therapy improved to a Beck Depression Inventory score ≤9 which was not significantly greater than that for the group receiving relaxation training.(73 % ) , so a unique effect was not demonstrated for cognitive behavioral therapy . The outcome for tricyclic antidepressant medication ( 29 % improved to criteria ) was significantly worse than that for cognitive behavioral therapy . The patient 's pretreatment initial expectancy was not predictive BACKGROUND Season-related subsyndromal depressive symptoms during winter are common among population s at high latitudes . Both physical exercise and exposure to bright light can relieve the fatigue and downturn of mood associated with the shortening length of day . Serum cholesterol level may be related to changes in mood , but the evidence is contradictory . Our objective was to compare the effect of aerobic exercise with or without bright-light exposure on health-related quality of life , mood , and serum lipids in a sample of relatively healthy adult subjects . METHOD A r and omized controlled trial was conducted with subjects allocated to group aerobics training in a gym with bright light ( 2500 - 4000 lux ) ( N = 40 ) or normal illumination ( N = 42 ) or to relaxation/stretching sessions in bright light as a control group ( N = 42 ) twice a week for a period of 8 weeks . Changes in mood were recorded using question naires at the beginning of the study , at weeks 4 and 8 . and at follow-up 4 months after the study . A blood sample was drawn before and after the 8-week intervention to measure the concentrations of serum lipids . RESULTS Ninety-eight subjects completed the 8-week study . Both exercise and bright light effectively relieved depressive symptoms . Bright light reduced atypical depressive symptoms more than exercise ( p = .03 ) , based on the atypical symptoms subscore of the Structured Interview Guide for the Hamilton Depression Rating Scale-Seasonal Affective Disorders Version Self-Rating Format . There were no significant differences between the study groups in the changes in serum lipid levels . CONCLUSION Bright light administered twice a week , alone or combined with physical exercise , seems to be a useful intervention for relieving seasonal mood slumps Fifty-three child and adolescent psychiatric patients with depressive disorders were r and omly allocated to brief cognitive-behaviour therapy ( CBT ) or to a control treatment , relaxation training . Forty-eight patients completed the treatment phase of the trial , which comprised 5 - 8 treatment sessions . Post-treatment assessment s showed a clear advantage of CBT over relaxation on measures of both depression and overall outcome . However , there were no significant differences between the treatments on comorbid anxiety and conduct symptoms . At follow-up , the differences between the groups were reduced , partly because of a high relapse rate in the DTP group and partly because subjects in the relaxation group continued to recover Recent studies have found that positive affect is associated with greater relative left frontal EEG activation and negative affect is associated with greater relative right frontal EEG activation . Further , chronically depressed adults typically display stable right frontal EEG activation . The present study investigated the effects of music on mood state and right frontal EEG activation associated with chronic depression . Fourteen chronically depressed female adolescents listened to rock music for a 23-minute session . These adolescents were compared with a control sample of chronically depressed female adolescents who were simply asked to sit and relax their minds and their muscles for the same time period . EEG was recorded during baseline , music , and postmusic for three minutes each , and saliva sample s were collected before and after the session to determine the effects of the music on stress hormone ( cortisol ) levels . No group differences or changes were noted for observed or reported mood state . However , cortisol levels decreased and relative right frontal activation was significantly attenuated during and after the music procedure . It was concluded that music had positive effects on the physiological and biochemical measures even though observed and self-reported mood did not change Background Combining bright light exposure and physical exercise may be an effective way of relieving depressive symptoms . However , relatively little is known about individual factors predicting either a good response or treatment failure . We explored background variables possibly explaining the individual variation in treatment response or failure in a r and omised trial . Methods Participants were volunteers of working-age , free from prior mental disorders and recruited via occupational health centres . The intervention was a r and omised 8-week trial with three groups : aerobics in bright light , aerobics in normal room lighting , and relaxation/stretching in bright light . Good response was defined as a 50 % decrease in the symptom score on either the Hamilton Depression Rating Scale ( HDRS ) or 8-item scale of atypical symptoms . Background variables for the analysis included sex , age , body-mass index , general health habits , seasonal pattern , and sleep disturbances . Results Complete data were received from 98 subjects ( 11 men , 87 women ) . Of them , 42 ( 5 men , 37 women ) were classified as responders on the HDRS . Overall , light had a significant effect on the number of responders , as assessed with the HDRS ( X2 = .02 ) . The number needed to treat ( NNT ) for light was 3.8 . Conclusions We investigated the effect of bright light and exercise on depressive symptoms . Problems with sleep , especially initial insomnia , may predict a good response to treatment using combined light and exercise . Bright light exposure and physical exercise , even in combination , seem to be well tolerated and effective on depressive symptoms BACKGROUND So-called atypical depressive symptoms ( carbohydrate craving , prolonged sleep , weight gain , increased appetite ) frequently emerge in association with low illumination to which people are ordinarily exposed indoors , or even outdoors at extreme latitudes in wintertime . Our objective was to analyse the effect of physical exercise alone or combined with bright light on mood and the health-related quality of life during winter . METHODS We carried out a r and omized controlled trial on 120 indoor employees in southern Finl and between November and January . The subjects were allocated to supervised fitness training under bright ( 2500 - 4000 lx ) or ordinary ( 400 - 600 lx ) light conditions in a gym 2 - 3 times weekly for 8 weeks , or supervised relaxation training once a week over the same period as active placebo . We collected question naire data on the changes in mood and health-related quality of life after 4 and 8 weeks of training , and after 4 months follow-up . RESULTS Fitness training in bright light result ed in greater relief from atypical depressive symptoms and more vitality than in ordinary room light . Compared with relaxation alone , the former regime improved general mental health and social functioning in addition to the improvement in depressive symptoms and vitality , whereas the latter only increased vitality . CONCLUSIONS Supervised physical exercise combined with exposure to bright light appears to be an effective intervention for improving mood and certain aspects of the health-related quality of life in wintertime . This effect appears unrelated to the history of season-dependent symptoms , being noticeable among healthy individuals The National Institute of Mental Health ( NIMH ) Treatment of Depression Collaborative Research Program ( Elkin et al. , Archives of General Psychiatry , 46 , 971 - 982 ; 1989 ) reported treatment-by-severity interactions favouring pharmacotherapy for more depressed out patients , on a minority of relevant comparisons . The present study reports secondary analyses from a similar , preexisting data set in which treatment-by-severity interactions are systematic ally investigated with depressed out patients treated either with nondirective psychotherapy , behaviour therapy , pharmacotherapy , or relaxation/placebo . Despite multiple severity measures and variable severity cut scores , no treatment was differentially effective in improving more severely depressed patients . Also , there was little difference across symptom severity levels in the proportions of recovered patients between treatment groups . Finally , dynamic cluster analysis demonstrated that the proportion of pharmacotherapy nonresponders ( 20 % ) did not differ from the proportion of nonresponders in behaviour therapy or placebo groups . It is concluded that this failure to replicate the NIMH trial findings can not be attributed to treatment differences , population s or statistical power . The suggestion that pharmacotherapy be the treatment of choice for more severely depressed out patients appears to be unjustified on the basis of available evidence Thirty-two depressed adolescent mothers received ten 30-minute sessions of massage therapy or relaxation therapy over a five-week period . Subjects were r and omly assigned to each group . Although both groups reported lower anxiety following their first and last therapy sessions , only the massage therapy group showed behavioral and stress hormone changes including a decrease in anxious behavior , pulse , and salivary cortisol levels . A decrease in urine cortisol levels suggested lower stress following the five-week period for the massage therapy group Objective : To evaluate the short-term effects of exercise in patients with major depression . Design : Prospect i ve , r and omised , controlled study . Setting : A university hospital . Patients : A consecutive series of 38 in patients with a major depression episode undergoing st and ard clinical antidepressant drug treatment . Interventions : Patients were r and omly assigned to an exercise ( walking , n = 20 ) or placebo ( low-intensity stretching and relaxation exercises , n = 18 ) group . Training was carried out for 10 days . Main outcome measurements : Severity of depression assessed with the Bech-Rafaelsen Melancholy Scale ( BRMS ) and the Center for Epidemiologic Studies Depression scale ( CES-D ) . Results : After 10 days , reduction of depression scores in the exercise group was significantly larger than in the placebo group ( BRMS : 36 % v 18 % ; CES-D : 41 % v 21 % ; p for both = 0.01 ) ; the proportion of patients with a clinical response ( reduction in the BRMS scores by more than six points ) was also larger for the exercise group ( 65 % v 22 % , p<0.01 ) . Conclusions : Endurance exercise may help to achieve substantial improvement in the mood of selected patients with major depression in a short time Treatment efficacy is typically evaluated by examining group means and pre-post change scores . Although informative , such analyses may obscure individual or subgroup differences in response ( outcome profiles ) . The present study used two different methods to define treatment outcome profiles -- rationally-derived criteria ( Frank et al. , Archives of General Psychiatry 48 , 851 - 855 , 1991 ) and dynamic clustering -- to evaluate four treatments of unipolar depression : behaviour therapy , amitriptyline , psychodynamic psychotherapy and relaxation training ( attention placebo ) . The profiling methods yielded similar results . Regardless of treatment , the majority of patients displayed either a recovery or nonremission outcome profile , with relatively few instances of remission followed by a recurrence of depression . These findings challenge the view that any of the treatments are associated with a strong tendency to relapse , at least over Output:	Three trials showed no significant difference between relaxation and psychological treatment on clinician-rated depression at post intervention ( SMD 0.29 ( 95 % CI -0.18 to 0.75)).Inconsistent effects were found when comparing relaxation training to medication and there were few data available comparing relaxation with complementary and lifestyle treatments . Relaxation techniques were more effective at reducing self-rated depressive symptoms than no or minimal treatment . However , they were not as effective as psychological treatment .
MS2721	*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 results are reported here of a long-term double-blind controlled clinical trial of disodium cromoglycate ( D.S.C.G. ) and isoprenaline , D.S.C.G. alone , isoprenaline alone , and a placebo given as a powder for inhalation in the treatment of severe bronchial asthma . At the end of one year 16 out of 20 patients on D.S.C.G.-isoprenaline remained on the allocated capsules , compared with 10 out of 15 on D.S.C.G. , 5 out of 20 on isoprenaline , and 3 out of 19 taking the placebo . The differences between each of the D.S.C.G.-isoprenaline and D.S.C.G. regimens compared with the isoprenaline and placebo regimens were statistically significant . After eight weeks on four capsules a day the patients in each group were allocated at r and om so that half continued on full dosage and half on a reducing regimen . At the end of the year there was no significant difference in the failure rate between patients allocated the full dosage and the patients on the reducing dosage . The capsules were well tolerated and toxicity to D.S.C.G. was not observed BACKGROUND Inhalation therapy with sodium cromoglycate is recommended as the first-line prophylactic treatment for moderate asthma in children . The availability of spacer devices with face-masks has extended the applicability of metered-dose inhalers to younger children . We studied the feasibility and effects of this therapy compared with placebo in children aged 1 - 4 years . METHODS 218 children aged 1 - 4 years with moderate asthma were recruited through 151 general practitioners between March , 1995 , and March , 1996 . They were r and omly assigned sodium cromoglycate ( 10 mg three times daily ) or placebo , given by inhaler with spacer device and face-mask for 5 months . Rescue medication ( ipratropium plus fenoterol aerosol ) was available during the baseline period of 1 month and the intervention period . Parents completed a daily symptom-score list . The primary outcome measure was the proportion of symptom-free days in months 2 to 5 . Analysis was by both intention to treat and on treatment . FINDINGS 167 ( 77 % ) children completed the trial . 131 ( 78 % ) of these children used at least 80 % of the recommended dose . Of the 51 children who stopped prematurely , 23 had difficulties with inhaled treatment . The mean proportion of symptom-free days for both groups was greater for the treatment period than for the baseline period ( 95 % CI for mean difference 5.1 to 17.5 cromoglycate , 11.9 to 23.3 placebo ) . However there were no differences between the sodium cromoglycate and placebo groups in the proportion of symptom-free days ( mean 65.7 [ SD 25.3 ] vs 64.3 [24.5]% ; 95 % CI for difference -8.46 to 5.70 ) or in any other outcome measure . INTERPRETATION Our study in a general practice setting shows that inhalation therapy with a spacer device and face-mask is feasible in a majority of children below the age of 4 years . However , long-term prophylactic therapy with inhaled sodium cromoglycate is not more effective than placebo in this age-group Summary A double-blind , cross-over trial of disodium cromoglycate was carried out over a period of 6 weeks in 6 children and 4 adults . The reliability of symptomatic assessment was established by demonstrating concordance between four independent observers who rated symptoms on a notionally continuous scale . Significant clinical improvement was found during disodium cromoglycate therapy . This was not necessarily matched by improvement in the FEV in individual patients . The study is in general agreement with the reports of Howell and Altounyan ( 1967 ) , Kennedy ( 1967 ) , Smith and Devey ( 1968 ) and Moran et al. ( 1968 ) A previous investigation by Lambert et al. , which used computer simulation to examine the influence of choice of prior distribution on inferences from Bayesian r and om effects meta- analysis , is critically examined from a number of viewpoints . The practical example used is shown to be problematic . The various prior distributions are shown to be unreasonable in terms of what they imply about the joint distribution of the overall treatment effect and the r and om effects variance . An alternative form of prior distribution is tentatively proposed . Finally , some practical recommendations are made that stress the value both of fixed effect analyses and of frequentist approaches as well as various diagnostic investigations A double-blind , placebo-controlled study was performed to determine the efficacy and safety of cromolyn sodium ( Intal ) administered to children by metered dose inhaler ( MDI ) . Prior to entry , subjects were well controlled on cromolyn sodium capsules by Spinhaler turbo-inhaler plus beta 2 agonists . An active control interval of 2 weeks on cromolyn sodium capsules was followed by a 4-week single-blind period on placebo capsules . Those subjects whose asthma worsened significantly on placebo entered a 10-week double-blind phase , r and omized to receive either cromolyn sodium ( 2 mg per dose ) or placebo by MDI . Diary data , physician evaluation , and pulmonary function tests were used to assess efficacy , and scores were compared with the baseline value at 2-week intervals . Forty children with asthma , 8 to 20 years of age , entered the study and 32 qualified for the r and omized phase . No significant differences existed between the treatment groups at baseline . Most comparative data favored the cromolyn sodium group over the course of the study . Significant differences ( p less than .05 ) were noted for diary scores of breathlessness and overall asthma severity . There was significant improvement at the final visit favoring the cromolyn sodium group in restriction on normal activity , FEV1 , and PEFR . The cromolyn sodium group also experienced a decreasing need for concomitant bronchodilators . Both groups preferred pressurized aerosol by MDI over powdered capsules by Spinhaler . ( Intal and Spinhaler are registered trademarks of Fisons Corporation . Cromolyn sodium is a recently introduced drug used in the prophylactic treatment of severe , perennial , bronchial asthma , particularly in the pediatric age group . In a multicenter trial , 276 chronic asthmatic patients of eight pediatric allergists entered a r and omized , double-blind , placebo-controlled , crossover study lasting 12 weeks . Test compounds of cromolyn sodium or placebo were inhaled four times a day , and daily scores were kept of symptom severity as well as frequency of use of other medications . Patients had statistically significant lower average daily symptom scores when treated with cromolyn sodium as compared to treatment with placebo . A strong subjective preference for cromolyn sodium was expressed by 60 % of those completing the trial , versus 9 % for placebo . The patients ' need for other symptomatic medications also dropped significantly during the cromolyn treatment period Abstract A double-blind cross-over sequential trial of a new antiallergic compound , disodium cromoglycate ( ' FPL670 ' , ' Intal ' ) was carried out over a period of 6 weeks in ten patients severely disabled with allergic bronchial asthma . There was a significant clinical improvement during administration of FPL670 plus isoprenaline in all patients compared with two periods in which isoprenaline alone was given . Spirometric improvement occurred in only four patients . Subsequent experience over periods up to 26 months with these and other patients has confirmed the therapeutic value and safety of FPL670 in the management of allergic bronchial asthma A year-long double-blind trial was carried out in 53 asthmatic children with severe perennial symptoms who were not receiving corticosteroids or corticotrophin . The treatment group were given disodium cromoglycate with isoprenaline ( Intal Co. ) while the placebo group were given lactose with isoprenaline four times daily . The groups were closely matched for clinical , physiological , and immunological features . Evaluation was based on the use of a diary and clinical and physiological investigations , including exercise tests . After one year 71 % of the treatment group were still well controlled while 76 % of the placebo group had dropped out because of inadequate control of symptoms . There was no rise in the rate of failure towards the end of the trial period and there were no seasonal variations in the failure rate . No important toxic effects were noted . It was impossible to predict the outcome of the trial in any given patient from his clinical , physiological , or immunological status at the beginning . However , the prevention of exercise-induced asthma by premedication with disodium cromoglycate in a laboratory exercise test did correlate well with the satisfactory clinical response to the drug Output:	All concluded that SCG was ineffective in paediatric asthma . Rather than having no effect , it is demonstrated that a considerable body of evidence favours SCG compared to placebo and , far from being ineffective , the drug appears to be effective particularly in older children .
MS2722	*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 Cushing 's disease is a rare debilitating endocrine disorder for which few prospect i ve interventional studies have been done . We report results of the first phase 3 trial assessing long-acting intramuscular pasireotide in patients with Cushing 's disease . METHODS In this phase 3 clinical trial we recruited patients aged 18 years or older with persistent , recurrent , or de-novo ( non-surgical c and i date s ) Cushing 's disease who had a mean urinary free cortisol ( mUFC ) concentration ( from three 24 h sample s ) of 1·5 - 5·0 times the upper limit of normal ( ULN ) , a normal or greater than normal morning plasma adrenocorticotropic hormone concentration , and a pituitary source of Cushing 's syndrome , from 57 sites across 19 countries . Exclusion criteria included previous pasireotide treatment , mitotane therapy within 6 months , and pituitary irradiation within 10 years . We r and omly allocated patients 1:1 ( block size of four ) using an interactive-response-technology system to intramuscular pasireotide 10 mg or 30 mg every 4 weeks for 12 months ( in the core phase ) . We stratified r and omisation by screening mUFC concentration ( 1·5 to < 2·0 × ULN and 2·0 - 5·0 × ULN ) . The dose could be uptitrated ( from 10 mg to 30 mg or from 30 mg to 40 mg ) at month 4 if the mUFC concentration was greater than 1·5 × ULN , and at month 7 , month 9 , or month 12 if the mUFC concentration was greater than 1·0 × ULN . Investigators , patients , site personnel , and those assessing outcomes were masked to dose group allocation . The primary endpoint was the proportion of patients in each group with an mUFC concentration of less than or equal to the ULN at month 7 . Efficacy analyses were based on intention to treat . This trial is registered with Clinical Trials.gov , number NCT01374906 . FINDINGS Between Dec 28 , 2011 , and Dec 9 , 2014 , we r and omly allocated 150 patients to receive pasireotide 10 mg ( 74 [ 49 % ] patients ) or 30 mg ( 76 [ 51 % ] patients ) . The primary efficacy endpoint was met by 31 ( 41·9 % [ 95 % CI 30·5 - 53·9 ] ) of 74 patients in the 10 mg group and 31 ( 40·8 % [ 29·7 - 52·7 ] ) of 76 in the 30 mg group . The most common adverse events were hyperglycaemia ( 36 [ 49 % ] in the 10 mg group and 36 [ 47 % ] in the 30 mg group ) , diarrhoea ( 26 [ 35 % ] and 33 [ 43 % ] ) , cholelithiasis ( 15 [ 20 % ] and 34 [ 45 % ] ) , diabetes mellitus ( 14 [ 19 % ] and 18 [ 24 % ] ) , and nausea ( 15 [ 20 % ] and 16 [ 21 % ] ) . Serious adverse events suspected to be study drug related were reported in eight ( 11 % ) patients in the 10 mg group and four ( 5 % ) in the 30 mg group . Two ( 3 % ) patients in the 30 mg group died during the study ( pulmonary artery thrombosis and cardiorespiratory failure ) ; neither death was judged to be related to the study drug . INTERPRETATION Long-acting pasireotide normalised mUFC concentration in about 40 % of patients with Cushing 's disease at month 7 and had a similar safety profile to that of twice-daily subcutaneous pasireotide . Long-acting pasireotide is an efficacious treatment option for some patients with Cushing 's disease who have persistent or recurrent disease after initial surgery or are not surgical c and i date s , and provides a convenient monthly administration schedule . FUNDING Novartis Pharma AG BACKGROUND Cabergoline is a long-acting dopamine receptor agonist used to treat prolactinomas . Identification of D(2 ) receptors in corticotroph tumors led to clinical trials of cabergoline therapy in limited cases of Nelson 's syndrome , ectopic ACTH-secreting tumors , and recently Cushing 's disease ( CD ) . OBJECTIVE To evaluate the long-term efficacy of cabergoline monotherapy in patients with CD . METHODS Retrospective analysis of non-r and omized clinical therapy with cabergoline in 30 patients with CD treated in academic centers of Buenos Aires and Montreal . Cabergoline was initiated at 0.5 - 1.0 mg/week and adjusted up to a maximal dose of 6 mg/week based on urinary free cortisol ( UFC ) levels . Complete response to cabergoline was defined as a sustained normalization of UFC with at least two normal values measured at 1 - 3 months interval ; partial response was defined as a decrease of UFC to < 125 % of the upper limit of normal , and treatment failure as UFC ≥ 125 % of it . RESULTS Within 3 - 6 months , complete response was achieved in 11 patients ( 36.6 % ) and partial response in 4 patients ( 13.3 % ) . After long-term therapy , nine patients ( 30 % ) remain with a complete response after a mean of 37 months ( range from 12 to 60 months ) with a mean dose of 2.1 mg/week of cabergoline . Two patients escaped after 2 and 5 years of complete response , but one patient transiently renormalized UFC after an increase in cabergoline dosage . No long-term response was maintained in four initial partial responders . CONCLUSIONS Cabergoline monotherapy can provide an effective long-term medical therapy for selected patients with CD , but requires close follow-up for dose adjustments Cushing 's syndrome ( CS ) is a serious condition requiring drug management in diverse clinical setting s. Fifty four patients ( 44 females , 10 males ) with CS , aged 14 - 63 , received ketoconazole ( KTZ ) prior to surgery ( n= 27 ) , as complementary therapy after surgery and /or radiotherapy ( n= 16 ) , or as primary treatment ( n= 11 ) . It was given at a 600 ( 500 - 600 ) mg/day ( median - Cl195 ) maintenance dose for periods ranging from 15 days to 13 years . Clinical signs , hepatic enzymes and urinary free cortisol ( UFC ) were evaluated before and during KTZ treatment . UFC normalised or decreased to subnormal values in 85 % of the patients , in 5 to 150 days after starting treatment ; although failing to normalise , UFC decreased to 12 - 48 % of pre-treatment values in the remaining patients . Clinical signs improved throughout . Side effects were adrenal insufficiency ( 18.5 % ) , reversible hepatic toxicity ( 11 % ) , allergic skin rash ( 5.5 % ) and gastric intolerance ( 3.7 % ) ; in 11 % of patients , an " escape phenomenon " was observed . Twenty-four out of the total ( 44.4 % ) were treated for prolonged periods , from one up to 13 years . In conclusion , this study confirms that KTZ is an effective and generally well tolerated treatment for CS particularly : a ) shortly before surgery , b ) because of persistent hypercortisolism after surgery or awaiting the results of radiotherapy , c ) as a reasonable option in patients with CS of unknown aetiology and , d ) as long-term therapy in any case of unsolved hypercortisolism after failure of current treatments CONTEXT AND OBJECTIVE The role of cabergoline in Cushing 's disease ( CD ) remains controversial . The experience is limited to case reports and few open studies that report the effects determined after ≥1 month of treatment . In prolactinomas and dopamine-responsive GH-secreting tumours , effects of cabergoline are seen within days or weeks . Here , we search ed for short-term effects of cabergoline in CD . DESIGN Twenty patients ( 19 naïve and one recurrent ) were included in a prospect i ve study . Cabergoline was administered in increasing doses of 0.5 - 5 mg/week over 6 weeks . METHODS Urinary free cortisol ( UFC ) 24 h , morning cortisol and ACTH , and salivary cortisol at 0800 , 1600 and 2300 h were determined once weekly throughout . Diurnal curves ( six sample s ) of serum cortisol were measured at start and end . RESULTS At study end , the median cabergoline dose was 5 mg , range 2.5 - 5 mg/week . The prolactin levels , markers of compliance , were suppressed in all patients . During the treatment , hypercortisolism varied , gradual and dose-dependent reductions were not seen . Five patients had a > 50 % decrease of UFC , three had a > 50 % rise of UFC . Salivary cortisol at 2300 h showed a congruent > 50 % change with UFC in two of the five cases with decreased UFC , and in one of the three cases with increased UFC . One patient with decreases in both UFC and 2300 h salivary cortisol also had a reduction in diurnal serum cortisol during the course of the study . CONCLUSIONS Cabergoline seems to be of little value in the management of CD . Only one patient had a response-like pattern . Given the known variability of disease activity in CD , this might represent a chance finding Cushing ’s disease ( CD ) is associated with increased morbidity and mortality . Until now , no medical treatment has been shown to be totally satisfactory when administrated alone . This study aim ed to assess the effectiveness of cabergoline with added ketoconazole and of the same combination in reverse , using urinary free cortisol ( UFC ) and late night salivary cortisol ( LNSC ) levels as biochemical markers of the treatments ’ efficacy in CD patients . A prospect i ve analysis conducted on 14 patients ( f/m = 12/2 ; median age 52 , range 33–70 years ) divided into two groups : 6 patients initially treated with cabergoline for 4–6 months ( rising from 0.5–1 mg/week up to 3.0 mg/week ) , after which ketoconazole was added ( group A ) ; and 8 patients first took ketoconazole alone for 4–6 months ( rising from 200 mg/day to 600 mg/day ) , then cabergoline was added ( group B ) . Patients were compared with 14 age-matched patients in prolonged remission after effective neurosurgery for CD . The combination therapy led to UFC normalization in 79 % of patients with no differences between the groups ; only one patient failed to respond at all . Neither drug succeeded in controlling the disease when taken alone . LNSC dropped when compared to baseline levels , but not to a significant degree ( p = 0.06 ) , and it remained significantly higher than in controls ( p = 0.0006 ) . Associating cabergoline with ketoconazole may represent an effective second-line treatment , achieving a satisfactory reduction in UFC levels and clinical improvement . Although the combined treatment lowered patients ’ LNSC levels , they remained higher than normal , indicating a persistent sub clinical hypercortisolism ; the implication s of this condition need to be considered . No differences emerged between the two treatment schedules BACKGROUND Cushing 's disease is associated with high morbidity and mortality . Pasireotide , a potential therapy , has a unique , broad somatostatin-receptor-binding profile , with high binding affinity for somatostatin-receptor subtype 5 . METHODS In this double-blind , phase 3 study , we r and omly assigned 162 adults with Cushing 's disease and a urinary free cortisol level of at least 1.5 times the upper limit of the normal range to receive subcutaneous pasireotide at a dose of 600 μg ( 82 patients ) or 900 μg ( 80 patients ) twice daily . Patients with urinary free cortisol not exceeding 2 times the upper limit of the normal range and not exceeding the baseline level at month 3 continued to receive their r and omly assigned dose ; all others received an additional 300 μg twice daily . The primary end point was a urinary free cortisol level at or below the upper limit of the normal range at month 6 without an increased dose . Open-label treatment continued through month 12 . RESULTS Twelve of the 82 patients in the 600-μg group and 21 of the 80 patients in the 900-μg group met the primary end point . The median urinary free cortisol level decreased by approximately 50 % by month 2 and remained stable in both groups . A normal urinary free cortisol level was achieved more frequently in patients with baseline levels not exceeding 5 times the upper limit of the normal range than in patients with higher baseline levels . Serum and salivary cortisol and plasma corticotropin levels decreased , and clinical signs and symptoms of Cushing 's disease diminished . Pasireotide was associated with hyperglycemia-related adverse events in 118 of 162 patients ; other adverse events were similar to those associated with other somatostatin analogues . Despite declines in cortisol levels , blood glucose and glycated hemoglobin levels increased soon after treatment initiation and then stabilized ; treatment with a glucose-lowering medication was Output:	Conclusions This meta- analysis shows that medication induces cortisol normalization effectively in a large percentage of patients .
MS2723	*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 / AIM To investigate the feasibility and safety of preoperative capecitabine , cetuximab and radiation in patients with MRI-defined locally advanced rectal cancer ( LARC , cT3/T4 ) . PATIENTS AND METHODS 31 patients with LARC were treated with cetuximab and capecitabine concomitantly with 45 Gy radiotherapy and resected by total mesorectal excision . Histopathological response and association with KRAS status was evaluated . RESULTS R0-resection was possible in 27 of 31 ( 86 % ) patients . No complete pathological remission was observed . Radiochemotherapy with capecitabine and cetuximab was safe to administer and diarrhea was the main toxicity . KRAS-status did not correlate to down-staging or pathological response concerning T- or N-stage . CONCLUSION Neoadjuvant therapy with capecitabine and cetuximab in combination with radiotherapy did not lead to complete pathological remission . Treatment tolerability was excellent and toxicity remained low . KRAS status did not influence treatment outcomes . Capecitabine in combination with radiotherapy remains a st and ard therapy for locally advanced rectal cancer Background We investigated tumor regression grading ( TRG ) as a prognostic marker and individual-level surrogate for disease-free survival ( DFS ) in patients with rectal carcinoma treated within the Chirurgische Arbeitsgemeinschaft fur Onkologie/Arbeitsgemeinschaft Radiologische Onkologie/Arbeitsgemeinschaft Internistische Onkologie (CAO/ARO/AIO)-04 r and omized trial . Methods TRG was recorded prospect ively using the Dworak classification in 1179 patients after preoperative fluorouracil-based chemoradiotherapy ( CRT ) with or without oxaliplatin . Multivariable analysis was performed using Cox regression models adjusted for treatment arm , resection status , and pathologic stage . Individual-level surrogacy of TRG for DFS was examined using the four Prentice criteria ( PC1 - 4 ) . All statistical tests were two-sided . Results With a median follow-up of 50 months , the addition of oxaliplatin to fluorouracil-based CRT led to statistically significantly improved three-year DFS ( 75.9 % , 95 % CI = 72.3 to 79.5 , vs 71.3 % , 95 % CI = 67.6 to 74.9 , P = .04 , PC 1 ) and a shift toward more advanced TRG groups ( P < .001 , PC 2 ) compared with CRT with fluorouracil alone . The three-year DFS was 64.6 % ( 95 % CI = 57.3 to 71.9 ) , 77.6 % ( 95 % CI = 74.5 to 80.7 ) , and 92.3 % ( 95 % CI = 88.4 to 96.2 ) for TRG 0 + 1 ( poor regression ) , TRG 2 + 3 ( intermediate regression ) , and TRG 4 ( complete regression ) , respectively ( P < .001 , PC 3 ) . TRG constituted an independent prognostic factor for DFS ( TRG 2 + 3 vs TRG 0 + 1 , HR = 0.68 , 95 % CI = 0.51 to 0.90 , P = .007 ) . Due to multicollinearity , TRG 4 and pathologic stage could not be tested within the same model . The treatment effect on DFS was captured by TRG , satisfying individual-level PC4 . Conclusions Higher TRG after preoperative CRT predicted a favorable long-term outcome . At the individual patient level , TRG was a surrogate marker for DFS . Further phase III trials are needed to vali date TRG as a surrogate at trial level BACKGROUND PARP inhibitors are currently evaluated in combination with radiotherapy and /or chemotherapy . As sensitizers , PARP inhibitors are active at very low concentrations therefore requiring highly sensitive pharmacodynamic ( PD ) assays . Current clinical PD-assays partly fail to provide such sensitivities . The aim of our study was to enable sensitive PD evaluation of PARP inhibitors for clinical sensitizer development . MATERIAL AND METHODS P BMC s of healthy individuals and of olaparib and radiotherapy treated lung cancer patients were collected for ELISA-based PD-assays . RESULTS PAR-signal amplification by ex vivo irradiation enabled an extended quantification range for PARP inhibitory activities after ex vivo treatment with inhibitors . This " radiation-enhanced-PAR " ( REP ) assay provided accurate IC50 values thereby also revealing differences among healthy individuals . Implemented in clinical radiotherapy combination Phase I trials , the REP-assay showed sensitive detection of PARP inhibition in patients treated with olaparib and establishes strong PARP inhibitory activities at low daily doses . CONCLUSIONS Combination trials of radiotherapy and novel targeted agent(s ) often require different and more sensitive PD assessment s than in the monotherapy setting . This study shows the benefit and relevance of sensitive and adapted PD-assays for such combination purpose s and provides proof of clinical ly relevant cellular PARP inhibitory activities at low daily olaparib doses PURPOSE To assess the efficacy of 2 different approaches to neoadjuvant chemoradiation for distal rectal cancers . METHODS AND MATERIAL S One hundred six patients with T3/T4 distal rectal cancers were r and omized in a phase 2 study . Patients received either continuous venous infusion ( CVI ) of 5-Fluorouracil ( 5-FU ) , 225 mg/m(2 ) per day , 7 days per week plus pelvic hyperfractionated radiation ( HRT ) , 45.6 Gy at 1.2 Gy twice daily plus a boost of 9.6 to 14.4 Gy for T3 or T4 cancers ( Arm 1 ) , or CVI of 5-FU , 225 mg/m(2 ) per day , Monday to Friday , plus irinotecan , 50 mg/m(2 ) once weekly × 4 , plus pelvic radiation therapy ( RT ) , 45 Gy at 1.8 Gy per day and a boost of 5.4 Gy for T3 and 9 Gy for T4 cancers ( Arm 2 ) . Surgery was performed 4 to 10 weeks later . RESULTS All eligible patients ( n=103 ) are included in this analysis ; 2 ineligible patients were excluded , and 1 patient withdrew consent . Ninety-eight of 103 patients ( 95 % ) underwent resection . Four patients did not undergo surgery for either disease progression or patient refusal , and 1 patient died during induction chemotherapy . The median time of follow-up was 6.4 years in Arm 1 and 7.0 years in Arm 2 . The pathological complete response ( pCR ) rates were 30 % in Arm 1 and 26 % in Arm 2 . Locoregional recurrence rates were 16 % in Arm 1 and 17 % in Arm 2 . Five-year survival rates were 61 % and 75 % and Disease-specific survival rates were 78 % and 85 % for Arm1 and Arm 2 , respectively . Five second primaries occurred in patients on Arm 1 , and 1 second primary occurred in Arm 2 . CONCLUSIONS High rates of disease-specific survival were seen in each arm . Overall survival appears affected by the development of unrelated second cancers . The high pCR rates with 5-FU and higher dose radiation in T4 cancers provide opportunity for increased R0 resections and improved survival The Stockholm III Trial r and omized patients with primary operable rectal cancers to either short‐course radiotherapy ( RT ) with immediate surgery ( SRT ) , short‐course RT with surgery delayed 4–8 weeks ( SRT‐delay ) or long‐course RT with surgery delayed 4–8 weeks . This preplanned interim analysis examined the pathological outcome of delaying surgery BACKGROUND Organ preservation is a concept proposed for patients with rectal cancer after a good clinical response to neoadjuvant chemotherapy , to potentially avoid morbidity and side-effects of rectal excision . The objective of this study was to compare local excision and total mesorectal excision in patients with a good response after chemoradiotherapy for lower rectal cancer . METHODS We did a prospect i ve , r and omised , open-label , multicentre , phase 3 trial at 15 tertiary centres in France that were experts in the treatment of rectal cancer . Patients aged 18 years and older with stage T2T3 lower rectal carcinoma , of maximum size 4 cm , who had a good clinical response to neoadjuvant chemoradiotherapy ( residual tumour ≤2 cm ) were central ly r and omly assigned by the surgeon before surgery to either local excision or total mesorectal excision surgery . R and omisation , which was done via the internet , was not stratified and used permuted blocks of size eight . In the local excision group , a completion total mesorectal excision was required if tumour stage was ypT2 - 3 . The primary endpoint was a composite outcome of death , recurrence , morbidity , and side-effects at 2 years after surgery , to show superiority of local excision over total mesorectal excision in the modified intention-to-treat ( ITT ) population ( expected proportions of patients having at least one event were 25 % vs 60 % for superiority ) . This trial was registered with Clinical Trials.gov , number NCT00427375 . FINDINGS From March 1 , 2007 , to Sept 24 , 2012 , 186 patients received chemoradiotherapy and were enrolled in the study . 148 good clinical responders were r and omly assigned to treatment , three were excluded ( because they had metastatic disease , tumour > 8 cm from anal verge , and withdrew consent ) , and 145 were analysed : 74 in the local excision group and 71 in the total mesorectal excision group . In the local excision group , 26 patients had a completion total mesorectal excision . At 2 years in the modified ITT population , one or more events from the composite primary outcome occurred in 41 ( 56 % ) of 73 patients in the local excision group and 33 ( 48 % ) of 69 in the total mesorectal excision group ( odds ratio 1·33 , 95 % CI 0·62 - 2·86 ; p=0·43 ) . In the modified ITT analysis , there was no difference between the groups in all components of the composite outcome , and superiority was not shown for local excision over total mesorectal excision . INTERPRETATION We failed to show superiority of local excision over total mesorectal excision , because many patients in the local excision group received a completion total mesorectal excision that probably increased morbidity and side-effects , and compromised the potential advantages of local excision . Better patient selection to avoid unnecessary completion total mesorectal excision could improve the strategy . FUNDING National Cancer Institute of France , Sanofi , Roche Pharma Background There is increasing interest in nonoperative management ( NOM ) for rectal cancer with complete clinical response ( cCR ) after neoadjuvant chemoradiation ( nCRT ) . Objective The aim of this systematic review was to summarize the available data on NOM , with the intention of formulating st and ardized protocol s on which to base future investigations . Methods A systematic review following the Preferred Reporting Items for Systematic Review s and Meta-Analyses ( PRISMA ) guidelines was conducted . A highly sensitive literature search identified all relevant studies published between January 2004 and December 2016 . Data extraction and quality assessment was performed independently by two authors , and resolved by consensus with a third review er . Results In total , 15 studies , including 920 patients , met the inclusion criteria ; 575 ( 62.5 % ) of these patients underwent NOM after cCR , with the remaining patients forming a surgical control group . The weighted mean follow-up was 39.4 ( 12.7 ) months in the NOM group and 39.8 ( 5.1 ) months in the surgery group . The pooled regrowth rate in the NOM group was 21.3 % at a mean of 15.6 ( 7.0 ) months . Surgical salvage was possible and was undertaken in 93.2 % of these patients . Overall survival in the NOM group was 91.7 % , while disease-free survival was 82.7 % . For the comparison proctectomy group , pooled rates of local recurrence , overall survival , and disease-free survival were 8.4 , 92.4 , and 87.5 % , respectively . Conclusion NOM may be a feasible option for surgically eligible rectal cancer patients with cCR after nCRT . Before such a strategy can be widely implemented , further prospect i ve data are required with st and ardized definitions , diagnostic criteria , and management protocol s , with an emphasis on shared patient – provider decision making and patient-centered outcomes BACKGROUND Further optimisation of present st and ard chemoradiation is needed in patients with locally advanced rectal cancer . Veliparib , an oral poly(ADP-ribose ) polymerase inhibitor , has been shown to enhance the antitumour activity of chemotherapy and radiotherapy in pre clinical models . We aim ed to establish the maximum tolerated dose and establish the recommended phase 2 dose of veliparib combined with neoadjuvant capecitabine and radiotherapy . METHODS This phase 1b , open-label , multicentre , dose-escalation study was done at six hospitals ( one in Australia and five in the USA ) . Patients were eligible if they were aged 18 years or more and were newly diagnosed Output:	The oral derivative capecitabine has practical advantages over 5-fluorouracil , with equal efficacy , but the addition of a second chemotherapeutic agent has yet to show a consistent significant efficacy benefit in r and omized clinical assessment .
MS2724	*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 Low heart rate variability ( HRV ) is associated with a higher risk of death in patients with heart disease and in elderly subjects and with a higher incidence of coronary heart disease ( CHD ) in the general population . Methods and Results We studied the predictive value of HRV for CHD and death from several causes in a population study of 14 672 men and women without CHD , aged 45 to 65 , by using the case-cohort design . At baseline , in 1987 to 1989 , 2-minute rhythm strips were recorded . Time-domain measures of HRV were determined in a r and om sample of 900 subjects , for all subjects with incident CHD ( 395 subjects ) , and for all deaths ( 443 subjects ) that occurred through 1993 . Relative rates of incident CHD and cause-specific death in tertiles of HRV were computed with Poisson regression for the case-cohort design . Subjects with low HRV had an adverse cardiovascular risk profile and an elevated risk of incident CHD and death . The increased risk of death could not be attributed to a specific cause and could not be explained by other risk factors . Conclusions Low HRV was associated with increased risk of CHD and death from several causes . It is hypothesized that low HRV is a marker of less favorable health Objective : Days of high ambient carbon dioxide ( CO ) have been associated with increased hospital admissions for cardiac disease . This study was conducted to determine if daily concentrations of CO and fine particulates ( PM2.5 ) are associated with daily changes in heart rate variability . Methods : Each of 36 adults with coronary artery disease had personal exposure to PM2.5 and CO measured along with heart rate variability for one 24-hour period each week for up to 10 weeks . Results : Among those not taking beta-receptor blockers , there was a positive association between the st and ard deviation of the R-to-R intervals and CO ( P = 0.02 ) . No effect was found for PM2.5 . Conclusions : Urban exposure to CO may exert a biologic effect on the heart , which may be modified by medications Objective Exposure to air pollution is associated with increases in cardiovascular morbidity and mortality . This study was undertaken to determine the effect of diesel exhaust inhalation on heart rhythm and heart rate variability in healthy volunteers and patients with coronary heart disease . Design and setting Double-blind r and omised crossover studies in a university teaching hospital . Patients 32 healthy non-smoking volunteers and 20 patients with prior myocardial infa rct ion . Interventions All 52 subjects were exposed for 1 h to dilute diesel exhaust ( particle concentration 300 μg/m3 ) or filtered air . Main outcome measures Heart rhythm and heart rate variability were monitored during and for 24 h after the exposure using continuous ambulatory electrocardiography and assessed using st and ard time and frequency domain analysis . Results No significant arrhythmias occurred during or following exposures . Patients with coronary heart disease had reduced autonomic function in comparison to healthy volunteers , with reduced st and ard deviations of the NN interval ( SDNN , p<0.001 ) and triangular index ( p<0.001 ) . Diesel exhaust did not affect heart rate variability compared with filtered air ( p>0.05 for all ) in healthy volunteers ( SDNN 101±6 vs 91±6 , triangular index 20±1 vs 21±1 ) or patients with coronary heart disease ( SDNN 47±5 vs 38±4 , triangular index 8±1 vs 7±1 ) . Conclusions Brief exposure to dilute diesel exhaust does not alter heart rhythm or heart rate variability in healthy volunteers or well-treated patients with stable coronary heart disease . Autonomic dysfunction does not appear to be a dominant mechanism that can explain the observed excess in cardiovascular events following exposure to combustion-derived air pollution Objective : To measure the inflammatory and autonomic responses of healthy humans and patients with coronary artery disease to controlled concentrations of two specific components of vehicle derived air pollution , carbon particles and sulphur dioxide ( SO2 ) . Methods : Placebo controlled , double blind , r and om order human challenge study examining the effects of carbon particles ( 50 μg/m3 ) and SO2 ( 200 parts per billion ( ppb ) ) on heart rate variability ( HRV ) and circulating markers of inflammation and coagulation in healthy volunteers and patients with stable angina . Results : In healthy volunteers , markers of cardiac vagal control did not fall in response to particle exposure but , compared with the response to air , increased transiently immediately after exposure ( root mean square of successive RR interval differences ( RMSSD ) 15 ( 5 ) ms with carbon particles and 4 ( 3 ) ms ) with air , p < 0.05 ) . SO2 exposure result ed in no immediate change but a significant reduction in HRV markers of cardiac vagal control at four hours ( RMSSD −2 ( 3.6 ) ms with air , −7 ( 2.7 ) ms with SO2 , p < 0.05 ) . No such changes were seen in patients with stable angina . Neither pollutant caused any change in markers of inflammation or coagulation at zero , four , or 24 hours . Conclusion : In healthy volunteers , short term exposure to pure carbon particles does not cause adverse effects on HRV or a systemic inflammatory response . The adverse effects of vehicle derived particulates are likely to be caused by more reactive species found on the particle surface . SO2 exposure does , however , reduce cardiac vagal control , a response that would be expected to increase susceptibility to ventricular arrhythmia Evidence from animal studies suggests that beta-blockers can act within the central nervous system to increase cardiac vagal motoneuron activity . We have attempted to determine whether such an effect is evident in healthy humans , by examining the effects of lipophilic and hydrophilic agents on heart rate variability and cardiac vagal reflexes . A total of 20 healthy volunteers took part in the study . Autonomic studies were performed after 72 h of treatment with placebo , atenolol or metoprolol in a blinded cross-over design . ECG recordings were taken at rest and during mental and orthostatic stress . Heart rate variability was measured in the time and frequency domains . The effects on heart rate of two opposing cardiac vagal reflexes were examined . Trigeminal stimulation causing vagal stimulation , and isometric forearm muscle contraction ( ' muscle heart reflex ' ) causing vagal inhibition , were performed alone and simultaneously . At rest , during mental stress and during trigeminal stimulation , beta-blocker therapy was associated with significantly increased high-frequency beat-to-beat heart rate variability when compared with placebo . There were no significant differences in effects on heart rate or heart rate variability between atenolol and metoprolol . Analysis of the muscle heart reflex , alone and with simultaneous trigeminal stimulation , showed that the magnitude of the R-R interval response was significantly greater after beta-blocker therapy compared with placebo , but the effects of atenolol and metoprolol were equivalent . beta-Blocker therapy increased cardiac vagal activity , as shown by measures of high-frequency heart rate variability and reflex studies . Lipophilic and hydrophilic beta-blockers appeared to be equally efficacious in increasing the cardiac vagal modulation of heart rate Summary Background Long-term exposure to pollution can lead to an increase in the rate of decline of lung function , especially in older individuals and in those with chronic obstructive pulmonary disease ( COPD ) , whereas shorter-term exposure at higher pollution levels has been implicated in causing excess deaths from ischaemic heart disease and exacerbations of COPD . We aim ed to assess the effects on respiratory and cardiovascular responses of walking down a busy street with high levels of pollution compared with walking in a traffic-free area with lower pollution levels in older adults . Methods In this r and omised , crossover study , we recruited men and women aged 60 years and older with angiographically proven stable ischaemic heart disease or stage 2 Global initiative for Obstructive Lung Disease ( GOLD ) COPD who had been clinical ly stable for 6 months , and age-matched healthy volunteers . Individuals with ischaemic heart disease or COPD were recruited from existing data bases or outpatient respiratory and cardiology clinics at the Royal Brompton & Harefield NHS Foundation Trust and age-matched healthy volunteers using advertising and existing data bases . All participants had abstained from smoking for at least 12 months and medications were taken as recommended by participants ' doctors during the study . Participants were r and omly assigned by drawing numbered disks at r and om from a bag to do a 2 h walk either along a commercial street in London ( Oxford Street ) or in an urban park ( Hyde Park ) . Baseline measurements of participants were taken before the walk in the hospital laboratory . During each walk session , black carbon , particulate matter ( PM ) concentrations , ultrafine particles , and nitrogen dioxide ( NO2 ) concentrations were measured . Findings Between October , 2012 , and June , 2014 , we screened 135 participants , of whom 40 healthy volunteers , 40 individuals with COPD , and 39 with ischaemic heart disease were recruited . Concentrations of black carbon , NO2 , PM10 , PM2.5 , and ultrafine particles were higher on Oxford Street than in Hyde Park . Participants with COPD reported more cough ( odds ratio [ OR ] 1·95 , 95 % CI 0·96–3·95 ; p<0·1 ) , sputum ( 3·15 , 1·39–7·13 ; p<0·05 ) , shortness of breath ( 1·86 , 0·97–3·57 ; p<0·1 ) , and wheeze ( 4·00 , 1·52–10·50 ; p<0·05 ) after walking down Oxford Street compared with Hyde Park . In all participants , irrespective of their disease status , walking in Hyde Park led to an increase in lung function ( forced expiratory volume in the first second [ FEV1 ] and forced vital capacity [ FVC ] ) and a decrease in pulse wave velocity ( PWV ) and augmentation index up to 26 h after the walk . By contrast , these beneficial responses were attenuated after walking on Oxford Street . In participants with COPD , a reduction in FEV1 and FVC , and an increase in R5–20 were associated with an increase in during-walk exposure to NO2 , ultrafine particles and PM2.5 , and an increase in PWV and augmentation index with NO2 and ultrafine particles . In healthy volunteers , PWV and augmentation index were associated both with black carbon and ultrafine particles . Interpretation Short-term exposure to traffic pollution prevents the beneficial cardiopulmonary effects of walking in people with COPD , ischaemic heart disease , and those free from chronic cardiopulmonary diseases . Medication use might reduce the adverse effects of air pollution in individuals with ischaemic heart disease . Policies should aim to control ambient levels of air pollution along busy streets in view of these negative health effects . Funding British Heart Foundation Epidemiological studies have shown that air pollution is associated with increased cardiovascular mortality . Although the pathophysiological mechanisms behind this association have remained largely unknown , it has been suggested that changes in cardiac autonomic function may play a role . In this study , we investigated the association between acute carbon monoxide ( CO ) exposure and cardiac autonomic function as measured by heart rate variability ( HRV ) in subjects with stable coronary artery disease . Twenty‐four hour ambulatory electrocardiographic recording with simultaneous continuous personal CO concentration monitoring was performed in six male patients with angiographically verified coronary artery disease three times with 1‐week intervals . Time domain measures of HRV were calculated for 5‐min segments before and during the CO exposure periods . For further analysis CO exposures were divided into low ( ≤2·7 p.p.m . ) and high ( > 2·7 p.p.m . ) CO exposure periods . The mean of maximum CO levels during 61 CO exposure periods was 4·6 p.p.m . ( SD 5·0 p.p.m . ) . High CO exposure was associated with an increase in the square root of the mean of the sum of the squares of differences between adjacent RR intervals ( r‐MSSD ) ( P = 0·034 ) . Heart rate remained unchanged during the CO exposure . In conclusion , acute CO exposure which represented most likely exposure derived from traffic seems to modify cardiac autonomic control in patients with stable coronary artery disease 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 Output:	In conclusion , there is strong evidence that air pollution can have adverse effects on cardiovascular function in persons living with CAD .
MS2725	*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 of the many computer re sources used in clinical teaching of dermatology and venereology for medical undergraduates are information-oriented and focus mostly on finding a " correct " multiple-choice alternative or free-text answer . We wanted to create an interactive computer program , which facilitates not only factual recall but also clinical reasoning . Methods Through continuous interaction with students , a new computerised interactive case simulation system , NUDOV , was developed . It is based on authentic cases and contains images of real patients , actors and healthcare providers . The student selects a patient and proposes questions for medical history , examines the skin , and suggests investigations , diagnosis , differential diagnoses and further management . Feedback is given by comparing the user 's own suggestions with those of a specialist . In addition , a log file of the student 's actions is recorded . The program includes a large number of images , video clips and Internet links . It was evaluated with a student question naire and by r and omising medical students to conventional teaching ( n = 85 ) or conventional teaching plus NUDOV ( n = 31 ) and comparing the results of the two groups in a final written examination . Results The question naire showed that 90 % of the NUDOV students stated that the program facilitated their learning to a large/very large extent , and 71 % reported that extensive working with authentic computerised cases made it easier to underst and and learn about diseases and their management . The layout , user-friendliness and feedback concept were judged as good/very good by 87 % , 97 % , and 100 % , respectively . Log files revealed that the students , in general , worked with each case for 60–90 min . However , the intervention group did not score significantly better than the control group in the written examination . Conclusion We created a computerised case simulation program allowing students to manage patients in a non-linear format supporting the clinical reasoning process . The student gets feedback through comparison with a specialist , eliminating the need for external scoring or correction . The model also permits discussion of case processing , since all transactions are stored in a log file . The program was highly appreciated by the students , but did not significantly improve their performance in the written final examination Introduction Physician empathy is a complex phenomenon known to improve illness outcomes ; however , few tools are available for deliberate practice of empathy . We used a virtual patient ( VP ) to teach empathic communication to first-year medical students . We then evaluated students ’ verbal empathy in a st and ardized patient ( SP ) interaction . Methods Seventy medical students , r and omly assigned to 3 separate study groups , interacted with ( 1 ) a control VP portraying depression , ( 2 ) a VP with a backstory simulating patient shadowing , or ( 3 ) a VP able to give immediate feedback about empathic communication ( empathy-feedback VP ) . Subsequently , the students interviewed an SP portraying a scenario that included opportunities to express empathy . All SP interviews were recorded and transcribed . The study outcomes were ( 1 ) the students ’ verbal response to the empathic opportunities presented by the SP , as coded by reliable assessors using the Empathic Communication Coding System , and ( 2 ) the students ’ responses as coded by the SPs , using a communication checklist . Results There were no significant differences in student demographics between groups . The students who interacted with the empathy-feedback VP showed higher empathy in the SP interview than did the students in the backstory VP and the control VP groups [ mean ( SD ) empathy scores coded on a 0–6 scale were 2.91 ( 0.16 ) vs. 2.20 ( 0.22 ) and 2.27 ( 0.21 ) , respectively ) . The difference in scores was significant only for the empathy-feedback VP versus the backstory VP group ( P = 0.027 ) . The SPs rated the empathy-feedback and the backstory VP groups significantly higher than the control VP group on offering empathic statements ( P < 0.0001 ) , appearing warm and caring ( P = 0.015 ) , and forming rapport ( P = 0.004 ) . Conclusions Feedback on empathy in a VP interaction increased students ’ empathy in encounters with SPs , as rated by trained assessors , whereas a simulation of patient shadowing did not . Both VP interventions increased students ’ empathy as rated by SPs , compared with the control VP group Objective To improve pain management practice s , we developed an online interactive continuing education ( CE ) program for primary care providers ( PCPs ) . This program follows the flow of clinical decision-making through simulated cases at critical pain treatment points along the pain treatment continuum . Design A r and omized controlled trial was conducted to test the efficacy of this program . Participants were r and omized to either the experimental condition or the control condition ( online , text-based CE program ) . Subjects A total of 238 primary care providers were recruited through hospitals , professional newsletters , and pain conferences . Results Participants in both conditions reported significantly improved scores on knowledge ( KNOW-PAIN 50 ) , attitudes ( CAOS ) , and pain practice behaviors ( PPBS ) scales over the four-month study . The experimental condition showed significantly greater change over time on the tamper-resistant formulations ( TRFs ) of opioids and dosing CAOS subscale compared with the control condition . Post hoc comparisons suggested that participants in the experimental condition were less likely to endorse use of opioid TRFs over time compared with the control condition . Exploratory analyses for potential moderators indicated a significant three-way interaction with time , condition , and discipline ( i.e. , physician vs other ) for the impediments and concerns attitudes subscale and the early refill behaviors subscale . Post hoc comparisons indicated that physicians in the experimental condition exhibited the greatest change in attitudes and the nonphysicians exhibited the greatest change in reported behaviors in response to requests for early refills . Conclusions Findings suggest online CE programs may positively impact PCPs ' knowledge , attitudes , and pain practice behaviors but provide minimal evidence for the value of including interactivity Background The concept of virtual patients ( VPs ) encompasses a great variety of predominantly case-based e-learning modules with different complexity and fidelity levels . Methods for effective placement of VPs in the process of medical education are sought . The aim of this study was to determine whether the introduction of a voluntary virtual patients module into a basic life support with an automated external defibrillator ( BLS-AED ) course improved the knowledge and skills of students taking the course . Methods Half of the students were r and omly assigned to an experimental group and given voluntary access to a virtual patient module consisting of six cases presenting BLS-AED knowledge and skills . Pre- and post-course knowledge tests and skills assessment s were performed , as well as a survey of students ' satisfaction with the VP usage . In addition , time spent using the virtual patient system , percentage of screen cards viewed and scores in the formative questions in the VP system throughout the course were traced and recorded . Results The study was conducted over a six week period and involved 226 first year medical students . The voluntary module was used by 61 ( 54 % ) of the 114 entitled study participants . The group that used VPs demonstrated better results in knowledge acquisition and in some key BLS-AED action skills than the group without access , or those students from the experimental group deliberately not using virtual patients . Most of the students rated the combination of VPs and corresponding teaching events positively . Conclusions The overall positive reaction of students and encouraging results in knowledge and skills acquisition suggest that the usage of virtual patients in a BLS-AED course on a voluntary basis is feasible and should be further investigated Objectives To compare medical students ’ and residents ’ knowledge retention of assessment , diagnosis and treatment procedures , as well as a learning experience , of patients with spinal trauma after training with either a Virtual Patient case or a video-recorded traditional lecture . Methods A total of 170 volunteers ( 85 medical students and 85 residents in orthopedic surgery ) were r and omly allocated ( stratified for student/resident and gender ) to either a video-recorded st and ard lecture or a Virtual Patient-based training session where they interactively assessed a clinical case portraying a motorcycle accident . The knowledge retention was assessed by a test immediately following the educational intervention and repeated after a minimum of 2 months . Participants ’ learning experiences were evaluated with exit question naires . A repeated- measures analysis of variance was applied on knowledge scores . A total of 81 % ( n = 138 ) of the participants completed both tests . Results There was a small but significant decline in first and second test results for both groups ( F(1 , 135 ) = 18.154 , p = 0.00 ) . However , no significant differences in short-term and long-term knowledge retention were observed between the two teaching methods . The Virtual Patient group reported higher learning experience levels in engagement , stimulation , general perception , and expectations . Conclusions Participants ’ levels engagement were reported in favor of the VP format . Similar knowledge retention was achieved through either a Virtual Patient or a recorded lecture Background E-learning and blended learning approaches gain more and more popularity in emergency medicine curricula . So far , little data is available on the impact of such approaches on procedural learning and skill acquisition and their comparison with traditional approaches . Objective This study investigated the impact of a blended learning approach , including Web-based virtual patients ( VPs ) and st and ard pediatric basic life support ( PBLS ) training , on procedural knowledge , objective performance , and self- assessment . Methods A total of 57 medical students were r and omly assigned to an intervention group ( n=30 ) and a control group ( n=27 ) . Both groups received paper h and outs in preparation of simulation-based PBLS training . The intervention group additionally completed two Web-based VPs with embedded video clips . Measurements were taken at r and omization ( t0 ) , after the preparation period ( t1 ) , and after h and s-on training ( t2 ) . Clinical decision-making skills and procedural knowledge were assessed at t0 and t1 . PBLS performance was scored regarding adherence to the correct algorithm , conformance to temporal dem and s , and the quality of procedural steps at t1 and t2 . Participants ’ self- assessment s were recorded in all three measurements . Results Procedural knowledge of the intervention group was significantly superior to that of the control group at t1 . At t2 , the intervention group showed significantly better adherence to the algorithm and temporal dem and s , and better procedural quality of PBLS in objective measures than did the control group . These aspects differed between the groups even at t1 ( after VPs , prior to practical training ) . Self- assessment s differed significantly only at t1 in favor of the intervention group . Conclusions Training with VPs combined with h and s-on training improves PBLS performance as judged by objective measures PURPOSE To assess the performance of interprofessional teams of radiologists , technologists , and nurses trained with high-fidelity h and s-on ( HO ) simulation and computer-based ( CB ) simulation training for contrast reaction management ( CR ) and teamwork skills ( TS ) . METHODS Nurses , technologists , and radiology residents were r and omized into 11 teams of three ( one of each ) . Six teams underwent HO training and five underwent CB training for CR and TS . Participants took written tests before and after training and were further tested using a high-fidelity simulation scenario . RESULTS HO and CB groups scored similarly on all written tests and each showed improvement after training ( P = .002 and P = .018 , respectively ) . During the final scenario test , HO teams tended to receive higher grade s than CB teams on CR ( 95 % versus 81 % , P = .17 ) and made fewer errors in epinephrine administration ( 0/6 versus 2/5 , P = .18 ) . HO and CB teams scored similarly on TS ( 51 % versus 52 % , P = .66 ) , but overall scores were lower for TS than for CR skills in both the HO ( P = .03 ) and CB teams ( P = .06 ) . HO training was more highly rated than CB as an effective educational tool ( P = .01 ) and for effectiveness at teaching CR and team communication skills ( P = .02 ) . CONCLUSIONS High-fidelity simulation can be used to both train and test interprofessional teams of radiologists , technologists , and nurses for both CR and TS and is more highly rated as an effective educational tool by participants than similar CB training . However , a single session of either type of training may be inadequate for mastering TS Aim The Virtual Ophthalmology Clinic ( VOC ) is an interactive web-based teaching module , with special emphasis on history taking and clinical reasoning skills . The purpose of this study was to determine the impact of VOC on medical students ’ learning . Methods A r and omised controlled trial ( RCT ) was conducted with medical students from the University of Sydney ( n=188 ) who were r and omly assigned into either an experimental ( n=93 ) or a control group ( n=95 ) . A pre- and post-test and student satisfaction question naire were administered . Twelve months later a follow-up test was conducted to determine the long-term retention rate of graduates . Results There was a statistically significant ( P<0.001 ) within-subject improvement pre- to post rotation in the number of correctly answered questions for both the control and experimental groups ( mean improvement for control 10 % , 95 % CI 1.3–2.6 , and for experimental 17.5 % , 95 % CI 3.0–4.0 ) . The improvement was significantly greater in the experimental group ( mean difference in improvement between groups 7.5 % , 95 % CI 0.8–2.3 , P<0.001 ) . At 12 months follow-up testing , the experimental group scored on average 1.6 ( 8 % ) ( 95%CI 0.4 to 2.7 , P=0.007 ) higher than the controls . Conclusion On the basis of a statistically significant improvement in academic performance and highly positive student feedback , the implementation of VOC may provide a means to address challenges to ophthalmic learning outcomes in an already crowded medical curriculum We intended to clarify the influence of student academic ability on the effectiveness of CAI , using data of a study to assess the effectiveness of a new type of CAI software , cyberPatient ( CP ) , Output:	Conclusions Low to modest and mixed evidence suggests that when compared with traditional education , virtual patients can more effectively improve skills , and at least as effectively improve knowledge . The skills that improved were clinical reasoning , procedural skills , and a mix of procedural and team skills . We found evidence of effectiveness in both high-income and low- and middle-income countries , demonstrating the global applicability of virtual patients .
MS2726	*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 advent of bisphosphonates advanced therapy for Paget 's disease , but more effective and convenient agents are needed to increase adherence . Zoledronic acid , a bisphosphonate administered as a single intravenous infusion , might meet these needs . METHODS In two identical , r and omized , double-blind , actively controlled trials of 6 months ' duration , we compared one 15-minute infusion of 5 mg of zoledronic acid with 60 days of oral risedronate ( 30 mg per day ) . The primary efficacy end point was the rate of therapeutic response at six months , defined as a normalization of alkaline phosphatase levels or a reduction of at least 75 percent in the total alkaline phosphatase excess . The results of the studies were pooled . RESULTS At six months , 96.0 percent of patients receiving zoledronic acid had a therapeutic response ( 169 of 176 ) , as compared with 74.3 percent of patients receiving risedronate ( 127 of 171 , P<0.001 ) . Alkaline phosphatase levels normalized in 88.6 percent of patients in the zoledronic acid group and 57.9 percent of patients in the risedronate group ( P<0.001 ) . Zoledronic acid was associated with a shorter median time to a first therapeutic response ( 64 vs. 89 days , P<0.001 ) . Higher response rates in the zoledronic acid group were consistent across all demographic , disease-severity , and treatment-history subgroups and with changes in other bone-turnover markers . The physical-component summary score of the Medical Outcomes Study 36-item Short-Form General Health Survey , a measure of the quality of life , increased significantly from baseline at both three and six months in the zoledronic acid group and differed significantly from those in the risedronate group at three months . Pain scores improved in both groups . During post-trial follow-up ( median , 190 days ) , 21 of 82 patients in the risedronate group had a loss of therapeutic response , as compared with 1 of 113 patients in the zoledronic acid group ( P<0.001 ) . CONCLUSIONS A single infusion of zoledronic acid produces more rapid , more complete , and more sustained responses in Paget 's disease than does daily treatment with risedronate Several Biophosphonates have been used as therapeutic agents for Paget 's bone disease . ( Chloro-4 phenyl)thiomethylene-bisphosphonate ( CIPsMBP ) has recently been shown to have significant antiosteoclastic activity while an affect of CIPsMBP on mineralization was only observed at high doses . We tested this drug for 6 months in 23 pagetic patients distributed in three groups . Gr 1 ( n = 5 ) receiving 200 mg/day showed a decrease of serum alkaline phosphatase ( SAP ) to 42 + /- 4 % ( p less than 0.01 ) of initial value ( 100 % ) while hydroxyprolinuria/creatinuria ratio ( OH/Cr ) dropped to 69 + /- 8 % of baseline . In 4 patients receiving 400 mg/day , SAP improved to 48 + /- 9 % of initial value ( p less than 0.01 ) and OH/Cr to 40 + /- 3 % ( p less than 0.01 ) . In the last group ( n = 14 ) receiving 200 mg/day for 3 months , and 400 mg/day thereafter up to the 6th month SAP decreased to 53 + /- 4 % and OH/Cr to 62 + /- 6 % of initial value ( p less than 0.01 ) . Clinical improvement was significant from the first month of treatment . No resistance ( mean decrease of SAP lower than 30 % ) was recorded and no radiological or clinical evidence of mineralization defect appeared . The clinical and biological tolerance was excellent throughout the study Summary Daily oral tablet bisphosphonate therapy for Paget ’s disease of bone may cause serious upper gastrointestinal adverse events . A once-weekly alendronate 280 mg oral buffered solution was compared with an alendronate 40 mg/day tablet . While both were similarly effective , the tablet appeared to be better tolerated in this study . Introduction Although daily doses of oral bisphosphonates are a generally safe and effective treatment for Paget ’s disease of bone ( PDB ) , some patients may experience upper gastrointestinal adverse events ( UGI AEs ) or find the dosing requirements inconvenient and become noncompliant . A once-weekly ( OW ) oral dose of bisphosphonate in buffered solution ( OBS ) may be as effective , better tolerated , and more convenient . Methods Sixty-three patients were r and omized to either alendronate ( ALN ) 280 mg OW OBS ( n = 42 ) or an ALN 40 mg/day tablet ( n = 21 ) during a 6-month , r and omized , double-blind , active-controlled trial . The primary endpoint was the mean percent decrease in total serum alkaline phosphatase ( total ALP ) from baseline at 6 months . Results There were no significant differences in total ALP between groups during the 6-month period . There was a higher incidence of clinical AEs in the ALN 280 mg OW OBS ( 79 % ) vs. the ALN 40 mg/day tablet group ( 67 % ) , including drug related AEs ( 48 % and 10 % , respectively ) , which led to study discontinuation ( 19.0 % and 10 % , respectively ) . Conclusions Although ALN 280 mg OW OBS was similarly effective as ALN 40 mg/day in reducing total ALP in patients with PDB , the ALN 40 mg/day tablet appears to be better tolerated than ALN 280 mg OW OBS Abstract The diphosphonate , sodium etidronate ( disodium ethane-1-hydroxy-1,1-diphosphonate ) ( E.H.D.P. ) , which inhibits the growth and dissolution of calcium phosphate crystals in vitro , was given at doses of 0 , 1 , 5 , 10 , or 20 mg . per kg . per day for up to 6 months to forty-seven patients with Paget 's disease of bone . There was a dose-related suppression of the raised alkaline phosphatase in plasma and total hydroxyproline in urine , and at 20 mg . per kg . per day nearly half of the patients had normal values at the end of treatment . A single course of E.H.D.P. could maintain biochemical remission for at least 2 years after stopping treatment . Bone biopsy specimens confirmed the suppression of the Paget 's disease . Increases in unmineralised osteoid were only seen in biopsy specimens taken after the higher doses of E.H.D.P. and were usually small . There was also a reversible rise in plasma-phosphate at 20 mg . per kg . per day . It is suggested that E.H.D.P. given for short periods could provide a simple and reliable oral therapy in those cases of Paget 's disease in which treatment is regarded as desirable Bisphosphonates are widely regarded as the treatment of choice for Paget 's disease of bone ( PDB ) because of their potent inhibitory effects on bone turnover , but the effects of bisphosphonate therapy on symptoms and complications of PDB have been little studied . Here we report the results of a r and omized trial that compared the effects of symptomatic treatment with intensive bisphosphonate therapy in a cohort of 1324 patients with PDB who were followed up for a median of 3 years ( range 2 to 5 years ) . The symptomatic treatment group was treated only if they had pagetic bone pain , for which they were first given analgesics or anti-inflammatory drugs , followed by bisphosphonates if they did not respond . The intensive group received repeat courses of bisphosphonates irrespective of symptoms with the aim of reducing and maintaining serum alkaline phosphatase ( ALP ) levels within the normal range . The endpoints were fracture , orthopedic surgery , quality of life , bone pain , and hearing thresholds . Serum ALP levels were significantly lower in the intensive treatment group than in with the symptomatic treatment group within 4 months of commencing treatment and remained lower throughout the study ( p < .001 ) . There was no difference between the groups in quality of life ( as assessed by the SF36 question naire ) , in overall bodily pain , or in pagetic bone pain . Hearing thresholds , as assessed by audiometry did not change significantly and did not differ between the treatment groups . Clinical fractures occurred in 46 of 661 patients ( 7.0 % ) in the intensive treatment group compared with 49 of 663 patients ( 7.4 % ) in the symptomatic treatment group , and orthopedic surgery was required in 50 of 661 patients ( 7.3 % ) in the intensive treatment group and in 55 of 663 patients ( 8.3 % ) in the symptomatic treatment group . These differences were not significant . Subgroup analyses of patients with elevated ALP levels at baseline and those who did or did not receive bisphosphonates during the study yielded similar results to those in the study group as a whole . We conclude that striving to maintain normal ALP levels with intensive bisphosphonate therapy confers no clinical advantage over symptom-driven management in patients with established PDB . Neither management strategy had a significant beneficial impact on pain or quality of life ( Clinical trial registration number IS RCT N12989577 ) Subjects ( 109 ) with symptomatic Paget 's disease of bone were treated with 5 , 10 , or 20 mg of sodium etidronate (EHDP)/kg body weight - day for 6 to 24 months . Significant decreases in serum alkaline phosphatase and urinary hydroxyproline were noted after 6 months of therapy ; no significant further improvement result ed after prolonged therapy . Some patients maintained biochemical remission after withdrawal of EHDP but others showed a relapse , related primarily to the pretreatment severity . Clinical improvement was noted in 61 % of the patients . Similar findings were seen after a second course of EHDP . No side-effects were noted in patients treated with 5 mg of EHDP/kg body weight - day . In patients treated with 10 or 20 mg of EHDP/kg body weight - day , severe diarrhea , bone pain , and nontraumatic fractures were noted in 3 , 13 , and 12 patients respectively . Quantitative histomorphometry showed mineralization delay in patients receiving 10 or 20 mg of EHDP/kg body weight - day but not in those receiving 5 mg/kg body weight - day . Five milligrams of EHDP/kg body weight - day was effective and appears to be safer than the higher doses The use of disodium ethane-1 hydroxy-1 , 1-diphosphonate ( EHDP ) therapy for Paget 's disease of bone was examined in 75 affected patients . Forty-eight patients received r and omly assigned oral doses of either 0 , 2.5 , 5 , 10 , or 20 mg/kg/day in a controlled , double-blind protocol , and the remainder received either 10 or 20 mg/kg/day in a non-r and om protocol . The clinical status of the patients and appropriate laboratory tests were evaluated before treatment and at frequent intervals during a six-month period of initial therapy . There were no significant changes in either urinary hydroxyproline or serum alkaline phosphatase in those patients receiving placebos , while both these parameters decreased significantly at all dose levels of EHDP , with the greatest decline noted in the highest dose group . However , statistical analysis of the data related to changes in symptoms in the double-blind study revealed that patients receiving the higher dose of EHDP ( 10 or 20 mg/kg/day ) had less favorable outcomes than those receiving the lower doses ( 2.5 or 5 mg/kg/day ) . The high does group had a relatively lower rate of symptom improvement and a relatively greater rate of deterioration than did the low dose group . Twenty-one of forty-nine patients followed for at least 18 months have shown a sustained suppression of their serum alkaline phosphatase and urinary hydroxyproline values for 12 months following cessation of EHDP , while therapy has been reinstituted for the other 28 patients because of increases in these measurements , with or without accompanying symptomatic deterioration . Eight patients sustained fractures through Pagetic bone during the period of study and all of these were treated with higher doses of EHDP . On the basis of the biochemical and clinical data in this study it appears that initial therapy of Paget 's disease of bone with 5 mg EHDP/kg/day maximizes benefits while minimizing possible adverse effects Paget ’s disease of bone is a relatively common condition of unknown aetiology characterized by an increase in bone turnover . Many forms of treatment have been advocated but at the present time only the calcitonins ( 2 , 4 , 7 ) and the diphosphonates ( 1 , 3 , 5 , 11 ) offer practical forms of specific therapy Alendronate , an aminobisphosphonate , is much more potent than etidronate , an older bisphosphonate , in inhibiting osteoclast-mediated bone resorption , and unlike etidronate , therapeutic doses of alendronate are not associated with abnormal mineralization . In the present study , we compared the effectiveness , safety , Output:	There was insufficient evidence to confirm or exclude differences in adverse effects of bisphosphonates ( RR 1.05 , 95 % CI 0.95 to 1.76 ; 2 studies , 437 participants ; low- quality evidence ) and treatment discontinuation ( 2 studies , 437 participants ) ( RR 2.04 , 95 % CI 0.43 to 9.59 ; 2 studies , 437 participants ; very low- quality evidence ) .Intensive versus symptomatic treatmentThere was no consistent evidence of difference to response in bone pain , bodily pain or quality of life in participants who received intensive versus symptomatic treatment . We found moderate- quality evidence that bisphosphonates improved pain in people with Paget 's disease of bone when compared with placebo . We found insufficient evidence of benefit in terms of pain or quality of life from intensive treatment .
MS2727	*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 Although cognitive-behavioral therapy for Unexplained Physical Symptoms ( UPS ) is effective in secondary care , studies done in primary care produced implementation problems and conflicting results . We evaluated the effectiveness of a cognitive-behavioral group training tailored to primary care patients and provided by a secondary community mental-health service reaching out into primary care . Methodology /Principal Findings The effectiveness of this training was explored in a r and omized controlled trial . In this trial , 162 patients with UPS classified as undifferentiated somatoform disorder or as chronic pain disorder were r and omized either to the training or a waiting list . Both lasted 13 weeks . The preservation of the training 's effect was analyzed in non-r and omized follow-ups , for which the waiting group started the training after the waiting period . All patients attended the training were followed-up after three months and again after one year . The primary outcomes were the physical and the mental summary scales of the SF-36 . Secondary outcomes were the other SF-36-scales and the SCL-90-R. The courses of the training 's effects in the r and omized controlled trial and the follow-ups were analyzed with linear mixed modeling . In the r and omized controlled trial , the training had a significantly positive effect on the quality of life in the physical domain ( Cohen 's d = 0.38;p = .002 ) , but this overall effect was not found in the mental domain . Regarding the secondary outcomes , the training result ed in reporting an improved physical ( Cohen 's d = 0.43;p = 0.01 ) , emotional ( Cohen 's d = 0.44;p = .0.01 ) , and social ( Cohen 's d = 0.36;p = 0.01 ) functioning , less pain and better functioning despite pain ( Cohen 's d = 0.51;p = < 0.001 ) , less physical symptoms ( Cohen 's d = −.23;p = 0.05 ) and less sleep difficulties ( Cohen 's d = −0.25;p = 0.04 ) than time in the waiting group . During the non-r and omized follow-ups , there were no relapses . Conclusions / Significance The cognitive-behavioral group training tailored for UPS in primary care and provided by an outreaching secondary mental-health service appears to be effective and to broaden the accessibility of treatment for UPS . Trial Registration TrialRegister.nl Abstract Objective : To examine the additional effect of cognitive behavioural therapy for patients with medically unexplained physical symptoms in comparison with optimised medical care . Design : R and omised controlled trial with follow up assessment s six and 12 months after the baseline evaluation . Setting : General medical outpatient clinic in a university hospital . Subjects : An intervention group of 39 patients and a control group of 40 patients . Interventions : The intervention group received between six and 16 sessions of cognitive behavioural therapy . Therapeutic techniques used included identification and modification of dysfunctional automatic thoughts and behavioural experiments aim ed at breaking the vicious cycles of the symptoms and their consequences . The control group received optimised medical care . Main outcome measures : The degree of change , frequency and intensity of the presenting symptoms , psychological distress , functional impairment , hypochondriacal beliefs and attitudes , and ( at 12 months of follow up ) number of visits to the general practitioner . Results : At six months of follow up the intervention group reported a higher recovery rate ( odds ratio 0.40 ; 95 % confidence interval 0.16 to 1.00 ) , a lower mean intensity of the physical symptoms ( difference −1.2 ; −2.0 to −0.3 ) , and less impairment of sleep ( odds ratio 0.38 ; 0.15 to 0.94 ) than the controls . After adjustment for coincidental baseline differences the intervention and control groups also differed with regard to frequency of the symptoms ( 0.32 ; 0.13 to 0.77 ) , limitations in social ( 0.35 ; 0.14 to 0.85 ) and leisure ( 0.36 ; 0.14 to 0.93 ) activities , and illness behaviour ( difference −2.5 ; −4.6 to −0.5 ) . At 12 months of follow up the differences between the groups were largely maintained . Conclusion : Cognitive behavioural therapy seems to be a feasible and effective treatment in general medical patients with unexplained physical symptoms Background Although Cognitive-Behavioral Therapy ( CBT ) is effective for Unexplained Physical Symptoms ( UPS ) , some therapists in clinical practice seem to believe that CBT outcome will diminish if psychiatric comorbidity is present . The result is that patients with a psychiatric comorbidity are redirected from treatment for UPS into treatment for mental health problems . To explore whether this selection and allocation are appropriate , we explored whether CBT outcomes in UPS could be predicted by variables assessed at baseline and used in routine- practice assessment s. Methods Patients ( n=162 ) with UPS classified as undifferentiated somatoform disorder or chronic pain disorder were followed up until one year after they had attended a CBT group training . The time-points of the follow-up were at the end of CBT ( immediate outcome ) , three months after CBT ( short-term outcome ) , and one year after CBT ( long-term outcome ) .CBT outcome was measured using the Physical Component Summary of the SF-36 , which was the primary outcome measure in the r and omized controlled trial that studied effectiveness of the CBT group training . Predictors were : 1 . ) psychological symptoms ( global severity score of SCL-90 ) , 2 . ) personality-disorder characteristics ( sum of DSM-IV axis II criteria confirmed ) , 3 . ) psychiatric history ( past presence of DSM-IV axis I disorders ) , and 4 . ) health-related quality of life in the mental domain ( mental component summary of SF-36 ) . The effect of this predictor set was explored using hierarchical multiple regression analyses into which these predictors had been entered simultaneously , after control for : a. ) pretreatment primary outcome scores , b. ) age , c. ) gender , d. ) marital status , and e. ) employment . Results The predictor set was significant only for short-term CBT outcome , where it explained 15 % of the variance . A better outcome was predicted by more psychological symptoms , fewer personality-disorder characteristics , the presence of a psychiatric history , and a better quality of life in the mental domain . Conclusions As the predictors do not seem to predict CBT outcome consistently over time , the need for selection and allocation of patients for CBT is doubtful . It seems that this would unnecessarily deprive patients of effective treatment . Trial registration Nederl and s Trial Register , Abstract Background Somatoform disorders are characterized by the presence of multiple somatic symptoms without an organic cause that completely explains their symptoms . These patients generate a high cost in health services . We aim to evaluate the effectiveness and feasibility of a cognitive-behaviour therapy ( CBT ) programme , administered in group and individual formats in primary care for patients who are diagnosed with abridged somatization disorder . Method / design Design : Multicentre , r and omized , controlled trial involving 3 groups , one of which is the control group consisting of st and ardized recommended treatment for somatization disorder in primary care ( Smith 's norms ) and the 2 others , the intervention groups , consisting of cognitive-behavioural therapy ( 10 sessions ) administered in individual format ( intervention group 1 ) or in group format ( intervention group 2 ) . Setting : 29 primary care health centres in the province of Zaragoza and 3 primary care health centres in the province of Mallorca , Spain . Sample : N = 204 patients , ( 68 in each of the three groups ) , aged 18–65 years , able to underst and and read Spanish , who fulfil Escobar 's criteria of Abridgged Somatization Disorder ( SSI 4,6 ) , stable with pharmacotherapy over the previous month , and who will remain stable for the next 3 months in the doctor 's opinion , having signed informed consent . Intervention : Control group : St and ardized recommended treatment for somatization disorder in primary care ( Smith 's norms ) . Intervention group : 10 weekly sessions of CBT , following a protocol design ed by Prof. Escobar 's group at UMDNJ , USA . There are 2 different treatment conditions : individual and group format . Measurements : Survey on the use of health services , number and severity of somatic symptoms , anxiety , depression , quality of life and clinical global impression . The interviewers will not know which group the patient belongs to ( blind ) . The assessment s will be carried out at baseline , post-treatment , 6 months and 12 post-treatment . Main variables : Utilization of health services , number and severity of somatic symptoms . Analysis : The analysis will be per intent to treat . We will use the general linear models of the SPSS v.15 statistical package , to analyse the effect of treatment on the result variable ( utilization of health services , number and severity of somatic symptoms ) . Discussion It is necessary to develop more effective psychological treatments for somatoform disorders . This r and omised clinical trial will determine whether cognitive behaviour therapy , both in group or in individual format , is effective for the treatment of these patients .Trial registration Current controlled trials IS RCT OBJECTIVE Our aim was to assess cost-effectiveness of mindfulness-based cognitive therapy ( MBCT ) compared with enhanced usual care ( EUC ) in treating patients with persistent medically unexplained symptoms(MUS ) . METHODS A full economic evaluation with a one year time horizon was performed from a societal perspective . Costs were assessed by prospect i ve cost diaries . Health-related Quality of Life was measured using SF-6D . Outcomes were costs per Quality -Adjusted Life Year ( QALY ) . Bootstrap simulations were performed to obtain mean costs , QALY scores and incremental cost-effectiveness ratios ( ICERs ) . RESULTS MBCT participants ( n=55 ) had lower hospital costs and higher mental health care costs than patients who received EUC ( n=41 ) . Mean bootstrapped costs for MBCT were € 6269 , and € 5617 for EUC ( 95 % uncertainty interval for difference : -€1576 ; € 2955 ) . QALYs were 0.674 for MBCT and 0.663 for EUC . MBCT was on average more effective and more costly than EUC , result ing in an ICER of € 56,637 per QALY gained . At a willingness to pay of € 80,000 per QALY , the probability that MBCT is cost-effective is 57 % . CONCLUSION Total costs were not statistically significantly different between MBCT and EUC . However , MBCT seemed to cause a shift in the use of health care re sources as mental health care costs were higher and hospital care costs lower in the MBCT condition . Due to the higher drop-out in the EUC condition the cost-effectiveness of MBCT might have been underestimated . The shift in health care use might lead to more effective care for patients with persistent MUS . The longer-term impact of MBCT for patients with persistent MUS needs to be further studied In order to determine the health effects of an intervention that reduces the cost of care for somatization disorder ( SD ) patients , 59 primary care physicians were r and omized to receive a psychiatric consultation letter providing treatment recommendations for 73 patients either at baseline or the end of the year-long study . Seventy of these patients ( 96 % ) were followed every 4 months for 1 year by a research assistant blind to r and omization . A year following the intervention , patients of experimental physicians reported greater physical capacity than patients of control physicians ( mean difference = 17.9 , 95 % CI 1.0 - 34.9 ) with a $ 466 reduction ( 95 % CI $ 132-$699 ) in health care charges . In addition to a net 21 % reduction in health care charges for the typical SD patient , the consultation letter improved physical functioning in a group of highly impaired subjects BACKGROUND Reattribution is frequently taught to general practitioners ( GPs ) as a structured consultation that provides a psychological explanation for medically unexplained symptoms . AIMS To determine if practice -based training of GPs in reattribution changes doctor-patient communication , thereby improving outcomes in patients with medically unexplained symptoms of 3 months ' duration . METHOD Cluster r and omised controlled trial in 16 practice s , 74 GPs and 141 patients with medically unexplained symptoms of 6 hours of reattribution training v. treatment as usual . RESULTS With training , the proportion of consultations mostly consistent with reattribution increased ( 31 v. 2 % , P=0.002 ) . Training was associated with decreased quality of life ( health thermometer difference -0.9 , 95 % CI -1.6 to -0.1 ; P=0.027 ) with no other effects on patient outcome or health contacts . CONCLUSIONS Practice -based training in reattribution changed doctor-patient communication without improving outcome of patients with medically unexplained symptoms The objective of this research was to identify determinants of the magnitude of intracluster correlation coefficients ( ICCs ) in cluster r and omized trials from the field of implementation research . A survey of experts was conducted to generate a priori hypotheses of factors that might affect ICC size . Hypotheses were tested on empirical estimates of ICCs calculated from 21 implementation research data sets , mainly from the UK . Effects of setting ( primary or secondary care ) , type of variable ( process or outcome ) , type of measurement ( objective or subjective ) , prevalence of outcome and size of cluster were tested . In total , 220 ICCs were available ( range 0 to 0.415 ) . Significant differences in ICC magnitude were found . The ICCs were significantly higher for process than for outcome variables , and for secondary care outcomes compared with primary care outcomes . The effects of prevalence and size were less clear cut . There was no evidence to suggest that type of measurement affected ICC size . In conclusion , accurate estimates of Output:	When all psychological therapies included this review were combined they were superior to usual care or waiting list in terms of reduction of symptom severity , but effect sizes were small . Compared with usual care or waiting list conditions , CBT reduced somatic symptoms , with a small effect and substantial differences in effects between CBT studies . The effects were durable within and after one year of follow-up . Compared with enhanced or structured care , psychological therapies generally were not more effective for most of the outcomes . Compared with enhanced care , CBT was not more effective . The intervention groups reported no major harms . In daily practice , there is also a substantial proportion of participants not willing to accept psychological treatments for somatoform disorders or MUPS .
MS2728	*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 Braune , S. , Riedel , A. , Schulte-Mönting , J. and Raczek , J. Influence of a Radiofrequency Electromagnetic Field on Cardiovascular and Hormonal Parameters of the Autonomic Nervous System in Healthy Individuals . Radiat . Res . 158 , 352–356 ( 2002 ) . The potential health risks of radiofrequency electromagnetic fields ( EMFs ) emitted by mobile phones are of considerable public interest . The present study investigated the hypothesis , based on the results of our previous study , that exposure to EMFs can increase sympathetic vasoconstrictor activity . Forty healthy young males and females underwent a single-blind , placebo-controlled protocol once on each of two different days . Each investigation included successive periods of placebo and EMF exposure , given in a r and omized order . The exposure was implemented by a GSM-like signal ( 900 MHz , pulsed with 217 Hz , 2 W ) using a mobile phone mounted on the right-h and side of the head in a typical telephoning position . Each period of placebo exposure and of EMF exposure consisted of 20 min of supine rest , 10 min of 70 ° upright tilt on a tilt table , and another 20 min of supine rest . Blood pressure , heart rate and cutaneous capillary perfusion were measured continuously . In addition , serum levels of norepinephrine , epinephrine , cortisol and endothelin were analyzed in venous blood sample s taken every 10 min . Similar to the previous study , systolic and diastolic blood pressure each showed slow , continuous , statistically significant increases of about 5 mmHg during the course of the protocol . All other parameters either decreased in parallel or remained constant . However , analysis of variance showed that the changes in blood pressure and in all other parameters were independent of the EMF exposure . These findings do not support the assumption of a nonthermal influence of EMFs emitted by mobile phones on the cardiovascular autonomic nervous system in healthy humans The present study used exercise testing to examine the effects of 60-Hz electric and magnetic field exposure . Eleven males , 21 - 29 years , were tested during four experimental sessions ( counterbalanced order and double-blind design ) . These included either 45-min exercise ( 50 % of VO2 max ) or no-exercise periods followed by either real field ( 9-kV/m , 16-A/m ) or sham exposure for 2 h in a 60-Hz human exposure facility . Exercise produced a decrease in plasma volume and increases ( p less than 0.05 ) in lactic acid , cortisol , growth hormone and testosterone levels , but these were not different under real and sham field conditions during the 2-h recovery periods . During no-exercise sessions , cardiac interbeat interval was increased ( p less than 0.05 ) , i.e. , heart rate was slower , when subjects were exposed to real fields . Our results suggest that future studies should focus on evaluation of the effects of 60-Hz fields on the entire process of exercise-induced activation and recovery This human exposure study examined the relationship between field strength and biological response and tested whether the exposure levels at which the greatest effects occur differ for different endpoints . Three matched groups of 18 men each participated in two 6 h exposure test sessions . All subjects were sham exposed in one session . In the other session , each group of subjects was exposed at a different level of combined electric and magnetic field strength ( low group:6 kV/m , 10 microT ; medium group:9 kV/m , 20 microT ; and high group : 12 kV/m , 30 microT ) . The study was performed double blind , with exposure order counterbalanced . Significant slowing of heart rate , as well as alternations in the latency and amplitude of event-related brain potential measures derived from the electro encephalogram ( EEG ) , occurred in the group exposed to the 9 kV/m , 20 microT combined field ( medium group ) . Exposure at the other field strength levels had no influence on cardiac measures and differential effects on EEG activity . Significant decrements in reaction time and in performance accuracy on a time estimation task were observed only in the low group . These results provide support for the hypothesis that humans may be more responsive to some combinations or levels of field strength than to others and that such differences in responsivity may depend , in part , on the endpoint of interest This study investigated the problem of the influence of 50 Hz magnetic field ( MF ) on human heart rate variability ( HRV ) . The exposure system was a commercial device for magnetotherapy , generating field of the strength of 500 microT at the center of the coil , 150 - 200 microT at the position of human subjects ' heart and 20 - 30 microT at the position of subjects ' head . The exposure protocol s , applied r and omly , were either " half hour MF-off/half hour MF-on " or " half hour MF-off/half hour MF-off . " The phonocardiographic ( PhCG ) signal of 15 volunteers were obtained during exposure and used for calculation of time-domain HRV parameters ( mean time between heart beats ( N-N ) , st and ard deviation of time between heart beats ( SDNN ) , and the number of differences of successive beat-to-beat intervals greater than 50 ms , divided by the total number of beat-to-beat intervals ( pNN50 ) ) and nonlinear HRV measures ( approximate entropy ( ApEn ) , detrended fluctuation scaling exponents ) . The protocol MF-off/MF-on was applied in nine subjects . Repeated measures ANOVA ( RMANOVA ) performed for Mf-off/MF-off protocol indicated no statistical difference among four 15 min intervals of HRV data ( P value > 20 % for all parameters except for N-N , where P = 3.7 % ) . RMANOVA followed by the post hoc Tukey test performed for Mf-off/MF-on protocol indicated a statistically significant difference during MF on for N-N ( 8 % increase , P < .1 % ) , SDNN ( 40 % increase , P = 1.1 % ) , and pNN50 ( 110 % increase , P < .1 % ) . The results of the analysis indicate that the changes of these parameters could be associated with the influence of MF Recent studies indicate that exposure to extremely low frequency magnetic fields ( ELF MFs ) influences human electroencephalographic ( EEG ) alpha activity and pain perception . In the present study we analyse the effect on electrical EEG activity in the alpha b and ( 8 - 13 Hz ) and on nociception in 40 healthy male volunteers after 90-min exposure of the head to 50 Hz ELF MFs at a flux density of 40 or 80 microT in a double-blind r and omized sham-controlled study . Since cardiovascular regulation is functionally related to pain modulation , we also measured blood pressure ( BP ) and heart rate ( HR ) during treatment . Alpha activity after 80 microT magnetic treatment almost doubled compared to sham treatment . Pain threshold after 40 microT magnetic treatment was significantly lower than after sham treatment . No effects were found for BP and HR . We suggest that these results may be explained by a modulation of sensory gating processes through the opioidergic system , that in turn is influenced by magnetic exposure This study investigates the effect of exposure to a mobile phone-like radiofrequency ( RF ) electromagnetic field on people with atopic dermatitis ( AD ) . Fifteen subjects with AD were recruited and matched with 15 controls without AD . The subjects were exposed for 30 min to an RF field at 1 W/kg via an indoor base station antenna attached to a 900 MHz GSM mobile phone . Blood sample s for ELISA analysis of the concentration of substance P ( SP ) , tumor necrosis factor receptor 1 ( TNF R1 ) , and brain derived neurotrophic factor ( BDNF ) in serum were drawn before and after the provocation ( exposure/sham ) . Baseline heart rate and heart rate variability , local blood flow , and electrodermal activity were also recorded . No significant differences between the subject groups were found for baseline neurophysiological data . The cases displayed a serum concentration of TNF R1 significantly higher than the control subjects and a significantly lower serum concentration of BDNF in the baseline condition . For SP there was no difference between groups . However , no effects related to RF exposure condition were encountered for any of the measured substances . As to symptoms , a possible correlation with exposure could not be evaluated , due to too few symptom reports . The result of the study does not support the hypothesis of an effect of mobile phone-like RF exposure on serum levels of SP , TNF R1 , and BDNF in persons with AD University students use mobile phones frequently . We previously showed that there was no association between mobile phone use and EMF health hazards among university students . As our previous study was based only on self-reported symptoms this double-blind study was design ed to answer two basic questions . Firstly , are self-reported hypersensitive individuals capable of sensing whether there is a real/sham microwave exposure ? Secondly , do hypersensitive patients show alterations in their biological parameters such as heart rate , respiration , and blood pressure during microwave exposure ? The study consisted of a preliminary screening phase and two subsequent complementary phases . In the 1st phase , 700 students were screened for EMF hypersensitivity . Fifty two participants were hypersensitive individuals but after applying the exclusion criteria only 28 students were invited to take part in the 2nd and 3rd phase of the study , but only 20 students ( 71.4 % ) declared their informed consent . In the 2nd phase , these self reported hypersensitive participants , were exposed/sham exposed to microwave radiation emitted from a mobile phone for 10 minutes and they were asked if they could sense the existence of microwave radiation . In the 3rd phase , all students were connected to ICU monitoring devices and their basic physiological parameters were recorded precisely . Among self-reported symptoms reported in our previous study , in this study only problem in concentration ( P < 0.05 ) and low back pain ( P < 0.05 ) were associated with mobile phone use . Furthermore , there was a significant association between the location of mobile phone during talk and the overall score of the severity of the symptoms ( P < 0.001 ) . When the participants were asked to report their perception about the real and sham exposures , only 5 students ( 25 % ) could discriminate the real exposure/sham exposure phases . This relative frequency can be only due to chance . In the 3rd phase all of the 20 participants were connected to intensive care unit monitors and the changes in their heart rate , respiration , and blood pressure during real/sham exposure were recorded . No statistically significant changes between the means of these parameters in real/sham exposure were observed . Our findings clearly confirm the results obtained inother provocative studies . These data also indicate the possible role of psychological factors in electromagnetic hypersensitivity The aim of the present study was to investigate the effect of exposure to a mobile phone-like radiofrequency ( RF ) electromagnetic field on persons experiencing subjective symptoms when using mobile phones ( MP ) . Twenty subjects with MP-related symptoms were recruited and matched with 20 controls without MP-related symptoms . Each subject participated in two experimental sessions , one with true exposure and one with sham exposure , in r and om order . In the true exposure condition , the test subjects were exposed for 30 min to an RF field generating a maximum SAR(1 g ) in the head of 1 W/kg through an indoor base station antenna attached to a 900 MHz GSM MP . The following physiological and cognitive parameters were measured during the experiment : heart rate and heart rate variability ( HRV ) , respiration , local blood flow , electrodermal activity , critical flicker fusion threshold ( CFFT ) , short-term memory , and reaction time . No significant differences related to RF exposure conditions were detected . Also no differences in baseline data were found between subject groups , except for the reaction time , which was significantly longer among the cases than among the controls the first time the test was performed . This difference disappeared when the test was repeated . However , the cases differed significantly from the controls with respect to HRV as measured in the frequency domain . The cases displayed a shift in low/high frequency ratio towards a sympathetic dominance in the autonomous nervous system during the CFFT and memory tests , regardless of exposure condition . This might be interpreted as a sign of differences in the autonomous nervous system regulation between persons with MP related subjective symptoms and persons with no such symptoms Terrestrial Trunked Radio ( TETRA ) technology ( " Airwave " ) has led to public concern because of its potential interference with electrical activity in the brain . The present study is the first to examine whether acute exposure to a TETRA base station signal has an impact on cognitive functioning and physiological responses . Participants were exposed to a 420 MHz TETRA signal at a power flux density of 10 mW/m(2 ) as well as sham ( no signal ) under double-blind conditions . Fifty-one people who reported a perceived sensitivity to electromagnetic fields as well as 132 controls participated in a double-blind provocation study . Forty-eight sensitive and 132 control participants completed all three sessions . Measures of short-term memory , working memory , and attention were administered while physiological responses ( blood volume pulse , heart rate , skin conductance ) were monitored . After applying exclusion criteria based on task performance for each aforementioned cognitive measure , data were analyzed for 36 , 43 , and 48 sensitive participants for these respective tasks and , likewise , 107,125 , and 129 controls . We observed no differences in cognitive performance between sham and TETRA exposure in either group ; physiological response also did not differ between the exposure conditions . These findings are similar to previous double-blind studies with other mobile phone signals ( 900 - 2100 MHz ) , which could not establish any clear evidence that mobile phone signals affect health or cognitive function Output:	Studies have indicated that EMFs produced at cell-phone frequencies cause no-effect on the heart . At greater EMF strengths or shorter exposures , the ability of the body to develop compensation mechanisms is reduced and the potential for heart-related effects increases . It is noteworthy that diseases of heart tissues such as myocardial ischemia can also be successfully treated using EMF .
MS2729	*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 High-dose melphalan plus autologous stem-cell transplantation ( ASCT ) is the st and ard approach in transplant-eligible patients with newly diagnosed myeloma . Our aims were to compare consolidation with high-dose melphalan plus ASCT versus chemotherapy ( cyclophosphamide and dexamethasone ) plus lenalidomide , and maintenance with lenalidomide plus prednisone versus lenalidomide alone . METHODS We did an open-label , r and omised , multicentre , phase 3 study at 59 centres in Australia , Czech Republic , and Italy . We enrolled transplant-eligible patients with newly diagnosed myeloma aged 65 years or younger . Patients received a common induction with four 28-day cycles of lenalidomide ( 25 mg , days 1 - 21 ) and dexamethasone ( 40 mg , days 1 , 8 , 15 , and 22 ) and subsequent chemotherapy with cyclophosphamide ( 3 g/m(2 ) ) followed by granulocyte colony-stimulating factor for stem-cell mobilisation and collection . Using a 2 × 2 partial factorial design , we r and omised patients to consolidation with either chemotherapy plus lenalidomide ( six cycles of cyclophosphamide [ 300 mg/m(2 ) , days 1 , 8 , and 15 ] , dexamethasone [ 40 mg , days 1 , 8 , 15 , and 22 ] , and lenalidomide [ 25 mg , days 1 - 21 ] ) or two courses of high-dose melphalan ( 200 mg/m(2 ) ) and ASCT . We also r and omised patients to maintenance with lenalidomide ( 10 mg , days 1 - 21 ) plus prednisone ( 50 mg , every other day ) or lenalidomide alone . A simple r and omisation sequence was used to assign patients at enrolment into one of the four groups ( 1:1:1:1 ratio ) , but the treatment allocation was disclosed only when the patient reached the end of the induction and confirmed their eligibility for consolidation . Both the patient and the treating clinician did not know the consolidation and maintenance arm until that time . The primary endpoint was progression-free survival assessed by intention-to-treat . The trial is ongoing and some patients are still receiving maintenance . This study is registered at Clinical Trials.gov , number NCT01091831 . FINDINGS 389 patients were enrolled between July 6 , 2009 , and May 6 , 2011 , with 256 eligible for consolidation ( 127 high-dose melphalan and ASCT and 129 chemotherapy plus lenalidomide ) and 223 eligible for maintenance ( 117 lenalidomide plus prednisone and 106 lenalidomide alone ) . Median follow-up was 52·0 months ( IQR 30·4 - 57·6 ) . Progression-free survival during consolidation was significantly shorter with chemotherapy plus lenalidomide compared with high-dose melphalan and ASCT ( median 28·6 months [ 95 % CI 20·6 - 36·7 ] vs 43·3 months [ 33·2 - 52·2 ] ; hazard ratio [ HR ] for the first 24 months 2·51 , 95 % CI 1·60 - 3·94 ; p<0·0001 ) . Progression-free survival did not differ between maintenance treatments ( median 37·5 months [ 95 % CI 27·8-not evaluable ] with lenalidomide plus prednisone vs 28·5 months [ 22·5 - 46·5 ] with lenalidomide alone ; HR 0·84 , 95 % CI 0·59 - 1·20 ; p=0·34 ) . Fewer grade 3 or 4 adverse events were recorded with chemotherapy plus lenalidomide than with high-dose melphalan and ASCT ; the most frequent were haematological ( 34 [ 26 % ] of 129 patients vs 107 [ 84 % ] of 127 patients ) , gastrointestinal ( six [ 5 % ] vs 25 [ 20 % ] ) , and infection ( seven [ 5 % ] vs 24 [ 19 % ] ) . Haematological serious adverse events were reported in two ( 2 % ) patients assigned chemotherapy plus lenalidomide and no patients allocated high-dose melphalan and ASCT . Non-haematological serious adverse events were reported in 13 ( 10 % ) patients assigned chemotherapy plus lenalidomide and nine ( 7 % ) allocated high-dose melphalan and ASCT . During maintenance , adverse events did not differ between groups . The most frequent grade 3 or 4 adverse events were neutropenia ( nine [ 8 % ] of 117 patients assigned lenalidomide plus prednisone vs 14 [ 13 % ] of 106 allocated lenalidomide alone ) , infection ( eight [ 8 % ] vs five [ 5 % ] ) , and systemic toxicities ( seven [ 6 % ] vs two [ 2 % ] ) . Non-haematological serious adverse events were reported in 13 ( 11 % ) patients assigned lenalidomide plus prednisone versus ten ( 9 % ) allocated lenalidomide alone . Four patients died because of adverse events , three from infections ( two during induction and one during consolidation ) and one because of cardiac toxic effects . INTERPRETATION Consolidation with high-dose melphalan and ASCT remains the preferred option in transplant-eligible patients with multiple myeloma , despite a better toxicity profile with chemotherapy plus lenalidomide . FUNDING Celgene Background High‐dose chemotherapy plus autologous stem‐cell transplantation has been the st and ard treatment for newly diagnosed multiple myeloma in adults up to 65 years of age . However , promising data on the use of combination therapy with lenalidomide , bortezomib , and dexamethasone ( RVD ) in this population have raised questions about the role and timing of transplantation . Methods We r and omly assigned 700 patients with multiple myeloma to receive induction therapy with three cycles of RVD and then consolidation therapy with either five additional cycles of RVD ( 350 patients ) or high‐dose melphalan plus stem‐cell transplantation followed by two additional cycles of RVD ( 350 patients ) . Patients in both groups received maintenance therapy with lenalidomide for 1 year . The primary end point was progression‐free survival . Results Median progression‐free survival was significantly longer in the group that underwent transplantation than in the group that received RVD alone ( 50 months vs. 36 months ; adjusted hazard ratio for disease progression or death , 0.65 ; P<0.001 ) . This benefit was observed across all patient subgroups , including those stratified according to International Staging System stage and cytogenetic risk . The percentage of patients with a complete response was higher in the transplantation group than in the RVD‐alone group ( 59 % vs. 48 % , P=0.03 ) , as was the percentage of patients in whom minimal residual disease was not detected ( 79 % vs. 65 % , P<0.001 ) . Overall survival at 4 years did not differ significantly between the transplantation group and the RVD‐alone group ( 81 % and 82 % , respectively ) . The rate of grade 3 or 4 neutropenia was significantly higher in the transplantation group than in the RVD‐alone group ( 92 % vs. 47 % ) , as were the rates of grade 3 or 4 gastrointestinal disorders ( 28 % vs. 7 % ) and infections ( 20 % vs. 9 % ) . No significant between‐group differences were observed in the rates of treatment‐related deaths , second primary cancers , thromboembolic events , and peripheral neuropathy . Conclusions Among adults with multiple myeloma , RVD therapy plus transplantation was associated with significantly longer progression‐free survival than RVD therapy alone , but overall survival did not differ significantly between the two approaches . ( Supported by Celgene and others ; IFM 2009 Study Clinical Trials.gov number , NCT01191060 . In a r and omized , phase 3 study , superior complete/near-complete response ( CR/nCR ) rates and extended progression-free survival were demonstrated with bortezomib-thalidomide-dexamethasone ( VTD ) versus thalidomide-dexamethasone ( TD ) as induction therapy before , and consolidation after , double autologous stem cell transplantation for newly diagnosed myeloma patients ( intention-to-treat analysis ; VTD , n = 236 ; TD , n = 238 ) . This per- protocol analysis ( VTD , n = 160 ; TD , n = 161 ) specifically assessed the efficacy and safety of consolidation with VTD or TD . Before starting consolidation , CR/nCR rates were not significantly different in the VTD ( 63.1 % ) and TD arms ( 54.7 % ) . After consolidation , CR ( 60.6 % vs 46.6 % ) and CR/nCR ( 73.1 % vs 60.9 % ) rates were significantly higher for VTD-treated versus TD-treated patients . VTD consolidation significantly increased CR and CR/nCR rates , but TD did not ( McNemar test ) . With a median follow-up of 30.4 months from start of consolidation , 3-year progression-free survival was significantly longer for the VTD group ( 60 % vs 48 % for TD ) . Grade 2 or 3 peripheral neuropathy ( 8.1 % vs 2.4 % ) was more frequent with VTD ( grade 3 , 0.6 % ) versus TD consolidation . The superior efficacy of VTD versus TD as induction was retained despite readministration as consolidation therapy after double autologous transplantation . VTD consolidation therapy significantly contributed to improved clinical outcomes observed for patients r and omly assigned to the VTD arm of the study . The study is registered at www . clinical trials.gov as # NCT01134484 The Nordic Myeloma Study Group conducted an open r and omized trial to compare bortezomib as consolidation therapy given after high-dose therapy and autologous stem cell transplantation ( ASCT ) with no consolidation in bortezomib-naive patients with newly diagnosed multiple myeloma . Overall , 370 patients were central ly r and omly assigned 3 months after ASCT to receive 20 doses of bortezomib given during 21 weeks or no consolidation . The hypothesis was that consolidation therapy would prolong progression-free survival ( PFS ) . The PFS after r and omization was 27 months for the bortezomib group compared with 20 months for the control group ( P = .05 ) . Fifty-one of 90 patients in the treatment group compared with 32 of 90 controls improved their response after r and omization ( P = .007 ) . No difference in overall survival was seen . Fatigue was reported more commonly by the bortezomib-treated patients in self-reported quality -of-life ( QOL ) question naires , whereas no other major differences in QOL were recorded between the groups . Consolidation therapy seemed to be beneficial for patients not achieving at least a very good partial response ( VGPR ) but not for patients in the ≥ VGPR category at r and omization . Consolidation with bortezomib after ASCT in bortezomib-naive patients improves PFS without interfering with QOL . This trial was registered at www . clinical trials.gov as # NCT00417911 BACKGROUND High-dose chemotherapy with autologous stem-cell transplantation is a st and ard treatment for young patients with multiple myeloma . Residual disease is almost always present after transplantation and is responsible for relapse . This phase 3 , placebo-controlled trial investigated the efficacy of lenalidomide maintenance therapy after transplantation . METHODS We r and omly assigned 614 patients younger than 65 years of age who had nonprogressive disease after first-line transplantation to maintenance treatment with either lenalidomide ( 10 mg per day for the first 3 months , increased to 15 mg if tolerated ) or placebo until relapse . The primary end point was progression-free survival . RESULTS Lenalidomide maintenance therapy improved median progression-free survival ( 41 months , vs. 23 months with placebo ; hazard ratio , 0.50 ; P<0.001 ) . This benefit was observed across all patient subgroups , including those based on the β(2)-microglobulin level , cytogenetic profile , and response after transplantation . With a median follow-up period of 45 months , more than 70 % of patients in both groups were alive at 4 years . The rates of grade 3 or 4 peripheral neuropathy were similar in the two groups . The incidence of second primary cancers was 3.1 per 100 patient-years in the lenalidomide group versus 1.2 per 100 patient-years in the placebo group ( P=0.002 ) . Median event-free survival ( with events that included second primary cancers ) was significantly improved with lenalidomide ( 40 months , vs. 23 months with placebo ; P<0.001 ) . CONCLUSIONS Lenalidomide maintenance after transplantation significantly prolonged progression-free and event-free survival among patients with multiple myeloma . Four years after r and om Output:	Our data suggest that , in NDMM patients treated with upfront ASCT , post-transplant consolidation may improve depth of response , but does not add to OS or PFS , compared to lenalidomide maintenance alone .
MS2730	*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 feasibility , safety , and efficacy of intravenous tissue plasminogen activator ( t-PA ) for patients with acute ischemic stroke in clinical practice need to be assessed . METHODS We initiated a prospect i ve open-label study at a university hospital and two community hospitals in Houston , Tex , immediately after the publication of the National Institute of Neurological Disorders and Stroke ( NINDS ) t-PA study . A total of 30 patients , age 32 to 90 years , were treated with 0.9 mg/kg of intravenous t-PA ( maximum dose , 90 mg ) within 3 hours of acute ischemic stroke between December 1995 and December 1996 . RESULTS Six percent ( 6 % ) of all patients hospitalized with ischemic stroke received intravenous t-PA at the university hospital and 1.1 % at the community hospitals . The rates of total , symptomatic , and fatal intracerebral hemorrhage were 10 % , 7 % , and 3 % . Thirty-seven percent ( 37 % ) of patients recovered to fully independent function . The average time from stroke onset to emergency department arrival was 57 minutes ; emergency department arrival to computed tomography scan 41 minutes ; and computed tomography scan to administration of treatment 59 minutes . CONCLUSIONS When treatment guidelines are carefully followed in an urban hospital setting , intravenous t-PA for acute ischemic stroke is feasible and shows safety and efficacy comparable to the results of the NINDS study Objective : To study the short and long term differences in outcome between patients ⩾80 years of age and those ⩽79 years of age who received intravenous recombinant tissue plasminogen activator ( iv rt-PA ) for acute stroke within the first 3 hours of symptom onset . Methods : We studied consecutive patients treated with iv rt-PA for acute stroke , with prospect i ve follow up of up to 3 years . Outcome measures included National Institutes of Health Stroke Scale ( NIHSS ) score , Barthel Index ( BI ) , modified Rankin score ( MRS ) , and stroke mortality . Patients were split into two groups : younger ( ⩽79 years ) and older ( ⩾80 years ) . Results : There were 65 patients in the younger cohort and 31 patients in the older . Older patients were more likely to present with more severe baseline stroke ( p = 0.04 ; odds ratio ( OR ) 3.04 ; 95 % confidence interval ( CI ) 1.03 to 8.98 ) . Stroke mortality at 90 days was 10.8 % in the younger and 32.3 % in the older cohort ( p = 0.01 ) . At 90 days ’ follow up , patients in the older cohort with more severe stroke ( NIHSS score ⩾11 ) were nearly 10 times more likely to have poor outcome compared with their younger counterparts presenting with severe stroke ( p = 0.001 ; OR = 10.36 ; 95 % CI 2.16 to 49.20 ) . Baseline stroke severity and age were the only independent and equal predictors for stroke outcome . No threshold was found for age or baseline stroke severity predicting outcome . Conclusion : Older patients presenting with more severe baseline stroke are much less likely to benefit from iv rt-PA as compared with their younger counterparts Background —Intravenous recombinant tissue plasminogen activator ( rtPA ) is an effective therapy for acute ischemic stroke , but it is associated with risk of intracerebral hemorrhage ( ICH ) . Our aim was to identify , in a large cohort of patients , readily available baseline factors that are associated with thrombolysis-related ICH . Methods and Results —In a multicenter retrospective and prospect i ve investigation of individual data from 1205 patients treated in routine clinical practice with intravenous rtPA within 3 hours of stroke symptom onset , 72 patients ( 6 % ) developed symptomatic ICH and 86 additional patients ( 7 % ) had asymptomatic ICH identified on a routine follow-up CT . In analyses based on clinical variables alone , the main attributes associated with ICH were a history of diabetes mellitus and cardiac disease , increasing stroke severity , advancing age , use of antiplatelet agents other than aspirin before stroke onset , and elevated pretreatment mean blood pressure . In additional analyses that incorporated baseline CT and laboratory findings ( in a subset of patients ) , the main associations were early ischemic CT changes , in particular if exceeding one third of middle cerebral artery territory ; increasing stroke severity ; diabetes mellitus or elevated serum glucose ; and lower platelet counts . Final independent attributes associated with parenchymatous hematoma , defined by purely radiologically based criteria , were similar to those of symptomatic ICH . Conclusions —Readily available factors can identify acute ischemic stroke patients at high and low risk for rtPA-related ICH . These factors require confirmation in a prospect i ve cohort before clinical implementation Background and Purpose — Iron overload has been associated with greater oxidative stress and brain injury in experimental cerebral ischemia and reperfusion . This study investigates whether high serum ferritin levels , as an index of increased cellular iron stores , are associated with poor outcome , hemorrhagic transformation , and brain edema after treatment with tissue plasminogen activator in patients with acute ischemic stroke . Methods — A total of 134 consecutive patients treated with intravenous tissue plasminogen activator were prospect ively studied in four centers . Serum ferritin levels were determined at baseline , 24 and 72 hours after treatment . Cranial computed tomography was performed on admission and at 24 to 36 hours after tissue plasminogen activator infusion . Stroke severity and outcome were evaluated by using the National Institute of Health Stroke Scale and the modified Rankin Scale . Results — Computed tomography showed hemorrhagic transformation in 27 patients ( hemorrhagic infa rct ion in 15 and parenchymal hematoma in 12 ; symptomatic in four ) and brain swelling with midline shift in 15 . Poor outcome ( modified Rankin Scale > 2 ) at 90 days was observed in 54.5 % of patients . Ferritin levels at baseline were higher in patients with poor outcome at 90 days ( median [ quartiles ] , 165 [ 98,307 ] versus 17 [ 12,37 ] ng/mL ; P<0.001 ) and in those who developed parenchymal hematoma ( P=0.006 ) , symptomatic hemorrhagic transformation ( P=0.008 ) , and severe brain edema ( P<0.001 ) . Serum ferritin levels higher than 79 ng/mL before tissue plasminogen activator treatment were independently associated with poor outcome ( OR , 117 [ 95 % CI , 25 to 557 ] ) . Conclusions — Increased body iron stores are associated with poor outcome , symptomatic hemorrhagic transformation , and severe edema in patients treated with tissue plasminogen activator after ischemic stroke . These findings suggest that iron overload may offset the beneficial effect of thrombolytic therapies Background and Purpose — Patients with right hemispheric strokes ( RHSs ) present later to an emergency department , have a lower chance to receive intravenous recombinant tissue plasminogen activator ( IV rt-PA ) , and have worse clinical outcomes than do patients with left hemispheric strokes ( LHSs ) . We analyzed outcomes after IV rt-PA with respect to the side of the affected hemisphere . Methods — A prospect i ve cohort of acute stroke patients was treated with IV rt-PA at the London Health Sciences Centre ( December 1998 to March 2003 ) . Differences between patients with RHS and LHS were identified by univariate analysis . Logistic-regression analysis was used to determine a subset of variables independently associated with major neurological improvement at 24 hours and good outcome at 3 months after treatment . Results — Of 219 stroke patients who received IV rt-PA , 165 had hemispheric strokes ( 68 RHSs and 97 LHSs ) . Patients with RHSs were less hypertensive ( P=0.001 ) and had lower pretreatment National Institutes of Health Stroke Scale ( NIHSS ) scores ( P=0.005 ) . LHS ( odds ratio [ OR ] , 2.29 ; 95 % CI , 1.14 to 4.59 ; P=0.019 ) , age ( OR , 0.96 ; 95 % CI , 0.93 to 0.99 ; P=0.012 ) , and pretreatment NIHSS ( OR , 0.83 ; 95 % CI , 0.78 to 0.89 ; P<0.0001 ) were independent predictors of 3-month outcome . Female sex ( OR , 3 ; 95 % CI , 1.53 to 5.90 ; P=0.001 ) and LHS ( OR , 2.07 ; 95 % CI , 1.05 to 4.08 ; P=0.03 ) were independent predictors of major neurological improvement at 24 hours after IV rt-PA . Conclusions — Despite higher pretreatment NIHSS , patients with LHSs have a 2-fold increased chance of a good outcome 3 months after rt-PA treatment compared with patients with RHSs . This gain can be clinical ly detected at 24 hours after treatment . These results need to be coupled with neuroimaging and hemodynamic characteristics known to influence stroke outcome Background and Purpose — The Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy ( SITS-MOST ) unadjusted results demonstrated that intravenous alteplase is well tolerated and that the effects were comparable with those seen in r and omized , controlled trials ( RCTs ) when used in routine clinical practice within 3 hours of ischemic stroke onset . We aim ed to identify outcome predictors and adjust the outcomes of the SITS-MOST to the baseline characteristics of RCTs . Methods — The study population was SITS-MOST ( n=6483 ) and pooled RCTs ( n=464 ) patients treated with intravenous alteplase within 3 hours of stroke onset . Multivariable , backward stepwise regression analyses ( until P≤0.10 ) were performed to identify the outcome predictors for SITS-MOST . Variables appearing either in the final multivariable model or differing ( P<0.10 ) between SITS-MOST and RCTs were included in the prediction model for the adjustment of outcomes . Main outcome measures were symptomatic intracerebral hemorrhage , defined as National Institutes of Health Stroke Scale deterioration ≥1 within 7 days with any hemorrhage ( RCT definition ) , mortality , and independency as defined by modified Rankin Score of 0 to 2 at 3 months . Results — The adjusted proportion of symptomatic intracerebral hemorrhage for SITS-MOST was 8.5 % ( 95 % CI , 7.9 to 9.0 ) versus 8.6 % ( 6.3 to 11.6 ) for pooled RCTs ; mortality was 15.5 % ( 14.7 to 16.2 ) versus 17.3 % ( 14.1 to 21.1 ) ; and independency was 50.4 % ( 49.6 to 51.2 ) versus 50.1 % ( 44.5 to 54.7 ) , respectively . In the multivariable analysis , older age , high blood glucose , high National Institutes of Health Stroke Scale score , and current infa rct ion on imaging scans were related to poor outcome in all parameters . Systolic blood pressure , atrial fibrillation , and weight were additional predictors of symptomatic intracerebral hemorrhage . Current smokers had a lower rate of symptomatic intracerebral hemorrhage . Disability before current stroke ( modified Rankin Score 2 to 5 ) , diastolic blood pressure , antiplatelet other than aspirin , congestive heart failure , patients treated in new centers , and male sex were related to high mortality at 3 months . Conclusions — The adjusted outcomes from SITS-MOST were almost identical to those in relevant RCTs and reinforce the conclusion drawn previously in the unadjusted analysis . We identified several important outcome predictors to better identify patients suitable for thrombolysis Background : Predictors of outcome and safety in intravenous thrombolysis within 3 h in clinical routine is a matter of ongoing debate . Available reports contain small patient numbers or summarize heterogeneous multicenter data . Methods : Four hundred and fifty patients received intravenous thrombolysis within 3 h after stroke . Pretreatment NIHSS score and detailed medical history were analyzed . Noncontrast CT was performed before thrombolysis , 24–36 h later and in case of clinical deterioration . Symptomatic intracranial hemorrhage ( SICH ; any bleeding with an NIHSS increase of ≧4 points ) and clinical outcome ( modified Rankin Scale , mRS ) after 3 months were recorded . Logistic regression identified parameters predictive of independence ( mRS 0–2 ) and SICH . Results : Median onset to admission , door to needle and onset to treatment time was 75 , 50 and 135 min , respectively . Direct presentation by emergency service ( 64 % ) was the fastest way of referral . Median pretreatment NIHSS was 11 points . Independence ( mRS 0–2 ) was reached by 53 % . Mortality was 11 % ( 7 % intracerebral , 4 % extracerebral complications ) . Logistic regression identified low Output:	These results suggest no gender difference in outcome among patients treated with intravenous rtPA
MS2731	*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 —Markers of systemic inflammation ( eg , C-reactive protein [ CRP ] and interleukin-6 [ IL-6 ] ) have been proposed to be “ nontraditional ” risk factors for cardiovascular disease in patients with type 2 diabetes mellitus . Matrix metalloproteinase-9 ( MMP-9 ) has been implicated in the pathogenesis of atherosclerotic plaque rupture , which raises the possibility of the use of MMP-9 levels as a marker for future myocardial infa rct ion or unstable angina . In vitro and animal studies suggest that thiazolidinediones can reduce the expression of these markers . The purpose of this analysis was to determine whether rosiglitazone alters serum concentrations of CRP , IL-6 , MMP-9 , and white blood cell count ( WBC ) and to examine the relationship of these effects with demographic and disease variables . Methods and Results —CRP , IL-6 , MMP-9 , and WBC were analyzed from stored frozen serum sample s obtained from patients with type 2 diabetes who completed a 26-week r and omized , double-blind , placebo-controlled study . After 26 weeks of rosiglitazone treatment , the percentage reductions in mean CRP , MMP-9 , and WBC levels were statistically significant compared with baseline and placebo ( P < 0.01 ) . The percentage reduction in mean IL-6 was small and similar in the rosiglitazone and placebo groups . The change in each inflammatory marker from baseline to week 26 was significantly correlated ( P < 0.05 ) with each of the other markers , as well as with the homeostasis model assessment estimate of insulin resistance . Conclusions —Rosiglitazone reduces serum levels of MMP-9 and the proinflammatory marker CRP in patients with type 2 diabetes , which indicates potentially beneficial effects on overall cardiovascular risk Ramipril improves cardiovascular outcome in patients with peripheral arterial disease ; however , the precise mechanisms of benefit remain to be eluci date d. The effect of ramipril on large-artery stiffness in patients with peripheral arterial disease was examined . In addition , we determined the effect of ramiprilat on extracellular matrix from human aortic smooth muscle cell culture . Forty patients with peripheral arterial disease were r and omized to receive ramipril , 10 mg once daily or placebo for 24 weeks . Arterial stiffness was assessed globally via systemic arterial compliance and augmentation index ( carotid tonometry and Doppler velocimetry ) , and regionally via carotid – femoral pulse wave velocity . Angiotensin-converting enzyme inhibition increased arterial compliance by 0.10±0.02 mL/mm Hg , ( P<0.001 , all probability values relative to placebo ) and reduced pulse wave velocity by 1.7±0.2 m/s ( P<0.001 ) , augmentation index by 4.1±0.3 % ( P<0.001 ) , and systolic blood pressure by 5±1 mm Hg ( P<0.001 ) . Ramipril did not reduce mean arterial pressure significantly compared with placebo ( P=0.59 ) . In cell culture , ramiprilat decreased collagen deposition by > 50 % and increased elastin and fibrillin-1 deposition by > 3- and 4-fold respectively ( histochemistry and immunohistochemistry ) . Fibrillin-1 gene expression was increased 5-fold ( real-time reverse-transcriptase polymerase chain reaction ) . Ramiprilat also reduced gene and protein ( Western ) expression of both matrix metalloproteinase (MMP)-2 and MMP-3 . In conclusion , ramipril promoted an elastogenic matrix profile that may contribute to the observed clinical reduction in large-artery stiffness and carotid pressure augmentation , which occurred independently of mean arterial blood pressure reduction in patients with peripheral arterial disease PURPOSE Early repair of abdominal aortic aneurysms ( AAA ) is particularly appropriate for those that are most likely to exp and . Our aim was to define features on computed tomography ( CT ) scanning associated with subsequent rapid aneurysm expansion . METHODS We review ed CT scans of 80 patients with AAA ( > 3.0 cm ) who underwent CT scanning of the abdomen and pelvis two times , at least 6 months apart , between 1986 and 1992 . The aneurysms initially measured 4.4 + /- 0.6 cm , and the mean interval between obtaining scans was 22 + /- 12 months . Clinical variables assessed included age , sex , medical risk factors , underlying cardiovascular and pulmonary diseases , and administration of beta blockers and lipid-lowering agents . Computer-aided measurements on each CT scan section included the maximal and minimal diameters and area of the aneurysm . Dimensions of the luminal thrombus and the arc of aneurysm wall covered by thrombus ( TARC ) . Maximal aneurysm dimensions were related to juxtarenal aortic and second lumbar vertebral body dimensions . RESULTS Mean aneurysm expansion was 0.26 + /- 0.25 cm/yr . CT scanning variables that correlated significantly with rate of expansion included the mean TARC ( r = 0.43 , p < 0.001 ) , thrombus volume fraction ( r = 0.37 , p < 0.001 ) , TARC on the largest aneurysm cross section ( r = 0.34 , p < 0.01 ) , and thrombus area fraction ( r = 0.30 , p < 0.01 ) . Rapid expansion ( > 0.5 cm/yr ) occurred in 15 ( 19 % ) aneurysms . The two predictors for rapid expansion on logistic regression analysis were mean TARC ( p < 0.005 ) and the presence of carotid artery disease ( p < 0.05 ) . CONCLUSION An increased AAA thrombus load is associated with a higher likelihood of rapid expansion and should weigh in favor of early surgical repair BACKGROUND Angiotensin-converting enzyme ( ACE ) inhibitors prevent the expansion and rupture of aortic aneurysms in animals . We investigated the association between ACE inhibitors and rupture in patients with abdominal aortic aneurysms . METHODS We did a population -based case-control study of linked administrative data bases in Ontario , Canada . The sample included consecutive patients older than 65 ( n=15,326 ) admitted to hospital with a primary diagnosis of ruptured or intact abdominal aortic aneurysm between April 1 , 1992 , and April 1 , 2002 . FINDINGS Patients who received ACE inhibitors before admission were significantly less likely to present with ruptured aneurysm ( odds ratio [ OR ] 0.82 , 95 % CI 0.74 - 0.90 ) than those who did not receive ACE inhibitors . Adjustment for demographic characteristics , risk factors for rupture , comorbidities , contraindications to ACE inhibitors , measures of health-care use , and aneurysm screening yielded similar results ( 0.83 , 0.73 - 0.95 ) . Consistent findings were noted in subgroups at high risk of rupture , including patients older than 75 years and those with a history of hypertension . Conversely , such protective associations were not observed for beta blockers ( 1.02 , 0.89 - 1.17 ) , calcium channel blockers ( 1.01 , 0.89 - 1.14 ) , alpha blockers ( 1.15 , 0.86 - 1.54 ) , angiotensin receptor blockers ( 1.24 , 0.71 - 2.18 ) , or thiazide diuretics ( 0.91 , 0.78 - 1.07 ) . INTERPRETATION ACE inhibitors are associated with a reduced risk of ruptured abdominal aortic aneurysm , unlike other antihypertensive agents . R and omised trials of ACE inhibitors for prevention of aortic rupture might be warranted Aortic aneurysm is the 10th leading cause of death in older men [ 1 ] , but fundamental issues about the cause and epidemiology of this condition remain unresolved . A fourfold variation in the prevalence of abdominal aortic aneurysm ( AAA ) has been seen among participants in screening programs [ 2 ] , and the traditional view that AAA is a manifestation of atherosclerosis has been challenged by recent studies that suggest a role for specific genetic factors [ 3 ] . Most information on the epidemiology of AAA has come from screening studies [ 4 - 10 ] . However , the studies that have reported on potential risk factors have screened fewer than 5500 patients each , result ing in too few cases for multivariable analysis . Two nested casecontrol studies have reported multiple risk factor analyses for aortic aneurysms [ 11 , 12 ] , but these studies were also relatively small ( one contained 41 and one contained 165 aneurysms ) , did not attempt to identify all cases of AAA in their study population s , did not consider such important factors as family history of AAA , and disagreed about the significance of such factors as height and serum cholesterol levels . To identify factors that are independently associated with AAA and to determine the prevalence of previously unrecognized AAA in defined demographic and risk groups , we collected and analyzed self-reported information from a large cohort of veterans who participated in a multicenter ultrasonographic screening program . Methods Participants The Aneurysm Detection and Management ( ADAM ) study is an ongoing r and omized clinical trial comparing two strategies for the management of AAA ( immediate surgery and surgery reserved for aneurysms that enlarge to 5.5 cm , enlarge rapidly , or cause symptoms ) in patients 50 to 79 years of age with asymptomatic AAAs 4.0 to 5.4 cm in diameter [ 13 ] . Ultrasonography screening clinics were established at the 15 participating Department of Veterans Affairs medical centers to support recruitment into the trial . Active patients at these centers ( that is , patients treated during the current or previous fiscal year and those who had future appointments ) who met the age criteria for the study were invited by mail to attend the clinic . Throughout the screening period , the letters were mailed in batches according to patient social security number using the continuously up date d administrative patient data at each participating center . A second mailing that was done at some centers excluded persons who had previously been seen in the screening clinic . Active patients at the participating centers were also accepted for screening on a walk-in basis ; patients 50 to 79 years of age were included in the analysis because they were members of the target population and eventually would have been invited to participate . Inadvertent repeated screenings were identified by patient social security number , and results of second screenings were excluded . Patients who reported previously having been told that they had an AAA were also excluded . We include data from patients who were screened from the beginning of the program in October 1992 through March 1995 . The study was approved by the human rights committee at the Veterans Affairs Cooperative Studies Program coordinating center and by the institutional review boards at the 15 participating centers . Assessment of Associated Factors Before ultrasonographic examination , all patients completed a brief question naire that asked about demographic information and possible risk factors for AAA . Patients were asked whether they had ever been told by a physician that they had the condition in question ( for example , high blood pressure ) . The question naire was developed for the study , tested at the participating centers , and revised accordingly before the study began . The reliability of the data from the self-reported question naire was assessed by comparing this data with data collected in the subset of screened patients who had an AAA and who were later included in the clinical trial . These data were recorded by a study nurse after discussion with the patient and review of the patient 's medical records . Ascertainment of Abdominal Aortic Aneurysm The abdominal aorta was measured above and below the renal arteries using a 3.5-MHz real-time sector scanner . The ultrasonographers were instructed to 1 ) scan the aorta in the anteroposterior and lateral planes and 2 ) report the maximum external diameter at the widest point of any dilatation for the suprarenal and infrarenal segments . The ultrasonographers met twice during the study period to review techniques and compare measurement distributions . Patients found to have an AAA or another suspected abnormality were referred for evaluation , and discrepancies between the results of subsequent testing and the results of the initial screening were reported back to the study ultrasonographer . Screening appointments for patients whose examinations were inadequate because of insufficient fasting were rescheduled . An infrarenal aortic diameter of 4.0 cm or larger is generally agreed to constitute AAA , but no method for defining a smaller AAA has gained wide acceptance [ 14 ] . Most investigators have used unadjusted aortic diameter ( with such cutoff points as 3.0 cm , which is known to be associated with risk for rupture [ 15 ] ) but this practice may exaggerate the prevalence of AAA in larger people . To avoid this problem , use of a ratio of infrarenal aortic diameter to suprarenal aortic diameter of 1.5 or greater has been proposed [ 14 ] . However , this method labels some small aortas as having an AAA and fails to account for aneurysmal dilatation of the suprarenal aorta . The latter problem has , in turn , been addressed by a proposal to define AAA as an aortic diameter more than 1.5 times the diameter that would be expected on the basis of age , sex , body size , and other factors . However , values for the expected diameter have not been well defined [ 14 ] . Therefore , we considered several definitions of AAA , including an Output:	Studies so far suggest a protective role for diabetes on the development of AAA .
MS2732	*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 : Oxaliplatin displays a frequent dose-limiting neurotoxicity due to its interference with neuron voltage-gated sodium channels through one of its metabolites , oxalate , a calcium chelator . Different clinical approaches failed in neurotoxicity prevention , except calcium-magnesium infusions . We characterized oxalate outcome following oxaliplatin administration and its interference with cations and amino acids . We then looked for genetic predictive factors of oxaliplatin-induced neurotoxicity . Experimental Design : We first tested patients for cations and oxalate levels and did amino acid chromatograms in urine following oxaliplatin infusion . In the second stage , before treatment with FOLFOX regimen , we prospect ively looked for variants in genes coding for the enzymes involved ( a ) in the oxalate metabolism , especially glyoxylate aminotransferase ( AGXT ) , and ( b ) in the detoxification glutathione cycle , glutathione S-transferase π , and for genes coding for membrane efflux proteins ( ABCC2 ) . Results : In the first 10 patients , urinary excretions of oxalate and cations increased significantly within hours following oxaliplatin infusion , accompanied by increased excretions of four amino acids ( glycine , alanine , serine , and taurine ) linked to oxalate metabolism . In a further 135 patients , a minor haplotype of AGXT was found significantly predictive of both acute and chronic neurotoxicity . Neither glutathione S-transferase π nor ABCC2 single nucleotide polymorphisms we looked for were linked to neurotoxicity . Conclusion : These data confirm the involvement of oxalate in oxaliplatin neurotoxicity and support the future use of AGXT genotyping as a pretherapeutic screening test to predict individual susceptibility to neurotoxicity Background The objective of this study was to evaluate the efficacy and toxicity of infusional 5-fluorouracil ( 5-FU ) , folinic acid and oxaliplatin ( modified FOLFOX-6 ) in patients with advanced gastric cancer ( AGC ) , as first-line palliative combination chemotherapy . We also analyzed the predictive or prognostic value of germline polymorphisms of c and i date genes associated with 5-FU and oxaliplatin . Methods Seventy-three patients were administered a 2 hour infusion of oxaliplatin ( 100 mg/m2 ) and folinic acid ( 100 mg/m2 ) followed by a 46 hour continuous infusion of 5-FU ( 2,400 mg/m2 ) . Genomic DNA from the patients ' peripheral blood mononuclear cells was extracted . Ten polymorphisms within five genes were investigated including TS , GSTP , ERCC , XPD and XRCC . Results The overall response rate ( RR ) was 43.8 % . Median time to progression ( TTP ) and overall survival ( OS ) were 6.0 months and 12.6 months , respectively . Toxicities were generally tolerable and manageable . The RR was significantly higher in patients with a 6-bp deletion homozygote ( -6 bp/-6 bp ) in TS-3'UTR ( 55.0 % vs. 30.3 % in + 6 bp/+6 bp or + 6 bp/-6 bp , p = 0.034 ) , and C/A or A/A in XPD156 ( 52.0 % vs. 26.1 % in C/C , p = 0.038 ) . The -6 bp/-6 bp in TS-3'UTR was significantly associated with a prolonged TTP and OS . In a multivariate analysis , the 6-bp deletion in TS-3'UTR was identified as an independent prognostic marker of TTP ( hazard ratio = 0.561 , p = 0.032 ) . Conclusion Modified FOLFOX-6 chemotherapy appears to be active and well tolerated as first line chemotherapy in AGC patients . The 6-bp deletion in TS-3'UTR might be a c and i date to select patients who are likely to benefit from 5-FU based modified FOLFOX-6 in future large scale trial A Valine residue at position 105 of the GSTP1 protein results in decreased enzyme activity . As nuclear GSTP1 activity decreases irinotecan cytotoxicity , Val-allele carriers may benefit more from irinotecan chemotherapy . Our aim was to investigate the association of GSTP1 genotype with treatment outcome of irinotecan . Progression-free survival ( PFS ) and toxicity were determined in 267 metastatic colorectal cancer ( MCRC ) patients who were treated with first-line capecitabine ( CAP ) plus irinotecan ( CAPIRI ) , or CAP single agent in a prospect i ve r and omised phase III trial ( CAIRO ) . GSTP1 genotype was determined by Pyrosequencing . Patients receiving CAP showed a PFS of 6.6 ( Ile/Ile ) , 6.0 ( Ile/Val ) and 6.5 months ( Val/Val ) ; compared to 7.0 ( Ile/Ile ) , 8.8 ( Ile/Val ) and 9.2 months ( Val/Val ) with CAPIRI . Median PFS was 2.7 months longer in Val-allele carriers treated with CAPIRI compared to CAP ( P=0.005 ) . Patients with the Ile/Ile genotype showed similar PFS with CAPIRI and CAP ( 7.0 compared to 6.6 months , P=0.972 ) . Toxicity did not differ significantly among genotypes . GSTP1 codon 105 polymorphism may be predictive for the response to irinotecan-based chemotherapy in patients with MCRC , with the Val-allele being associated with a better outcome . Ile/Ile genotype patients do not appear to benefit from the addition of irinotecan to CAP Objective In Japan , there had been no prospect i ve clinical studies conducted in terms of modified FOLFOX6 + bevacizumab therapy . We performed a post-marketing Phase II multicenter clinical study to examine the efficacy and safety of this regimen as first-line therapy for Japanese patients with advanced/recurrent colorectal cancer . Methods Bevacizumab ( 5 mg/kg ) was administered intravenously , and then oxaliplatin ( 85 mg/m2 ) and levofolinate calcium ( 200 mg/m2 ) were infused intravenously over 2 h. Subsequently , a bolus dose of 5-fluorouracil ( 400 mg/m2 ) was injected , followed by infusion of 5-fluorouracil ( 2400 mg/m2 ) for 46 h. This regimen was repeated every 2 weeks until 24 cycles unless there was disease progression , unacceptable toxicity or patient refusal . The primary end point was the response rate . Results Among the 70 patients enrolled , two patients withdrew the study before treatment , and 68 patients were eligible for analysis of efficacy and safety . The response rate was 51.5 % ( 95 % confidence interval : 39.0–63.8 % ) . The median progression-free survival and median overall survival time were 12.6 months ( 95 % confidence interval : 10.4–14.5 months ) and 28.5 months [ 95 % confidence interval : 23.1 months–(not applicable ) ] , respectively . There were no treatment-related deaths observed . The most common Grade 3 and 4 adverse events included neutropenia in 35.3 % of the patients , peripheral neuropathy in 16.2 % and hypertension in 16.2 % . All adverse events were manageable and tolerable . The exploratory analysis of polymorphisms of three genes , ERCC1 , XPD and GSTP1 , did not show any trends in terms of correlation with the efficacy or safety of modified FOLFOX6 + bevacizumab therapy . Conclusions Modified FOLFOX6 + bevacizumab therapy was manageable and tolerable in Japanese patients , achieving a high response rate We investigated 17 polymorphisms in 11 genes ( TS , MTHFR , ERCC1 , XRCC1 , XRCC3 , XPD , GSTT1 , GSTP1 , GSTM1 , ABCC1 , ABCC2 ) for their association with the toxicity of fluoropyrimidines and oxaliplatin in colorectal cancer patients enrolled in a prospect i ve r and omized trial of adjuvant chemotherapy . The TOSCA Italian adjuvant trial was conducted in high-risk stage II – III colorectal cancer patients treated with 6 or 3 months of either FOLFOX-4 or XELOX adjuvant chemotherapy . In the concomitant ancillary pharmacogenetic study , the primary endpoint was the association of polymorphisms with grade 3–4 CTCAE toxicity events ( grade 2–4 for neurotoxicity ) . In 517 analyzed patients , grade ≥ 3 neutropenia and grade ≥ 2 neurotoxicity events occurred in 150 ( 29 % ) and in 132 patients ( 24.8 % ) , respectively . Diarrhea grade ≥ 3 events occurred in 34 ( 6.5 % ) patients . None of the studied polymorphisms showed clinical ly relevant association with toxicity . Hopefully , genome-wide association studies will identify new and more promising genetic variants to be tested in future studies Objectives We aim ed to evaluate the efficacy and safety of combination therapy of Endostar ( recombinant human endostatin ) and S-1 combined with oxaliplatin ( SOX ) in patients with advanced gastric cancer . Methods In this r and omized , controlled trial , 165 late-stage gastric cancer patients were assigned to the experimental arm with Endostar in combination with SOX ( 80 patients ) and the control arm with SOX alone ( 85 patients ) . The end points of this study included progression-free survival , response rate , and disease-control rate . Results There was no statistically significant difference in response rate between the experimental arm and the control arm ( 53.8 % vs 42.4 % , P=0.188 ) . The difference in disease-control rate was also statistically insignificant between the two arms ( 85.0 % vs 72.9 % , P=0.188 ) . Progression-free survival in the experimental arm was significantly higher than that in the control arm ( 15.0 months vs 12.0 months , P=0.0001 ) . Common adverse events included immunosuppression , gastrointestinal distress , and neuropathy . There was no statistical difference in the incidences of adverse events . Conclusion Combination therapy of Endostar and SOX provides therapeutic benefits to advanced gastric cancer patients , with tolerable adverse effects Oxaliplatin and irinotecan have proven effective in the treatment of gastric cancer . We attempted to determine whether single nucleotide polymorphisms in ERCC1 , GST , TS and UGT1A1 predicted overall survival in gastric cancer patients receiving FOLFOX and /or FOLFIRI chemotherapy . Total genomic DNA was extracted from the whole blood of patients . The PCR-restriction fragment length polymorphism technique was applied in order to detect the known variant sites of ERCC1 , GST , TS and UGT1A1 . The response rate of FOLFOX ( N=75 ) was 24 % . Grade 3 - 4 neutropenia and neurotoxicity were observed at frequencies of 34.7 and 16 % , respectively . TTP and OS of first-line administration of FOLFOX ( N=35 ) were 3.1 months ( 95 % CI , 0.1 - 6.1 months ) and 13.9 months ( 95 % CI , 12.2 - 15.6 months ) , respectively . Only the GSTM1 positive genotype exhibited a significantly better time to progression ( P=0.023 ) . However , significant genotypic variation of TS , GST and ERCC1 , which was assumed to affect the activity of oxaliplatin , was not observed to affect RR , toxicity and overall survival . The response rate of FOLFIRI ( N=74 ) was 23 % . Grade 3 - 4 neutropenia and diarrhea were observed in 55.4 and 9.5 % of cases , respectively . TTP and OS of first-line administration of FOLFIRI ( N=33 ) was 4.9 months ( 95 % CI , 3.5 - 6.4 months ) and 19.0 months ( 95 % CI , 8.5 - 29.5 months ) . The low expression type ( 2R/2R , 2R/3C and 3C/3C ) of TS was associated with a high incidence of grade > or=3 neutropenia . However , significant genotypic variation of UGT1A1 , which was assumed to affect irinotecan toxicity , was not observed to affect RR , toxicity or survival . In this study , the GSTM1 positive genotype evidence d a significantly better time to progression in cases of advanced gastric cancer being treated with FOLFOX . The low expression type ( 2R/2R , 2R/3C and 3C/3C ) of TS was associated with a high incidence of grade > or=3 neutropenia in cases of advanced gastric cancer treated with FOLFIRI The discovery of pharmacogenomic markers in colorectal cancer ( CRC ) could be setting -specific . FOLFOX4 is employed in the adjuvant and metastatic setting in CRC . This prospect i ve study is aim ed to vali date in the adjuvant setting the pharmacogenomic markers of toxicity reported Output:	After pooling all the eligible studies , we identified significant associations of GSTP1 Ile105Val polymorphism with chemotherapy-related tumor response ( G vs. A : OR 1.697 , 95 % CI 1.191–2.418 ; GG vs. AA : OR 2.804 , 95 % CI 1.414–5.560 ; AG vs. AA : OR 1.540 , 95 % CI 1.011–2.347 ; GG vs. AAAG : OR 2.139 , 95 % CI 1.256–3.641 ) , PFS ( GG vs. AA , HR 0.640 , 95 % CI 0.455–0.900 ; AGGG vs. AA : HR 0.718 , 95 % CI 0.562–0.919 ) , and OS ( AG vs. AA : HR 0.857 , 95 % CI 0.746–0.986 ; GG vs. AA : HR 0.679 , 95 % CI 0.523–0.882 ; AGGG vs. AA : HR 0.663 , 95 % CI 0.542–0.812 ) in gastric and colorectal cancers and no significant association was found between the polymorphism with toxicity . Conclusions GSTP1 Ile105Val polymorphism was associated with tumor response , PFS , and OS in gastric and colorectal cancers after chemotherapy
MS2733	*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 " Dry lab " facilities are integral to laparoscopy training , but access is often limited due to the high costs of video-laparoscopy equipment . We assessed the effectiveness of a cheap and simple training model compared to conventional video-laparoscopy for basic training using a r and omised , blinded study . METHODS Thirty-six third-year medical students without previous surgical skills were r and omised into two groups : group A students were taught basic laparoscopy skills using a conventional video-laparoscopy pelvic trainer and group B students were taught similar techniques using a cardboard box with a cut-out top to allow light and visualisation . Participants in group B had one eye obscured to reduce their stereoscopic vision . After eight sessions of training amounting to 24h , the two groups were assessed by a blinded adjudicator on set tasks using both the video-laparoscopy pelvic trainer and the cardboard box . Accuracy , timing and depth perception were assessed and the results compared . RESULTS There was no significant difference in performance scores or times between the two groups in any of the parameters when tested on the cardboard box . However , when assessed on the video trainer , the cardboard box-trained group had significantly faster times with equivalent scores in the majority of tasks . CONCLUSION For basic laparoscopic training the cardboard box , costing nothing , is a simple and effective alternative , which can be used in conjunction with sophisticated video-laparoscopy equipment costing thous and s of dollars Background Laparoscopic suturing is one of the most difficult tasks in endoscopic surgery , requiring extensive training . The aim of this study was to determine the transfer validity of knot-tying training on a virtual-reality ( VR ) simulator to a realistic laparoscopic environment . Methods Twenty surgical trainees underwent basic eye – h and coordination training on a VR simulator ( SIMENDO , DelltaTech , Delft , the Netherl and s ) until predefined performance criteria were met . Then , they were r and omized into two groups . Group A ( the experimental group ) received additional training with the knot-tying module on the simulator , during which they had to tie a double laparoscopic knot ten times . Group B ( controls ) did not receive additional manual training . Within a week the participants tied a double knot in the abdominal cavity of an anaesthetized porcine model . Their performance was captured on digital video and coded . Objective analysis parameters were : time taken to tie the knot and number of predefined errors made . Subjective assessment s were also made by two laparoscopic surgeons using a global rating list with a five-point Likert scale . Results Trainees in group A ( n = 9 ) were significantly faster than the controls ( n = 10 ) , with a median of 262 versus 374 seconds ( p = 0.034 ) . Group A made a significantly lower number of errors than the controls ( median of 24 versus 36 errors , p = 0.030 ) . Subjective assessment s by the laparoscopic experts did not show any significant differences in economy of movement and erroneous behavior between the two groups . ConclusionS urgical trainees who received knot-tying training on the VR simulator were faster and made fewer errors than the controls . The VR module is a useful tool to train laparoscopic knot-tying . Opportunities arose to improve simulator-based instruction that might enhance future training Background : The study aim was to compare the effectiveness of virtual reality and computer-enhanced video-scopic training devices for training novice surgeons in complex laparoscopic skills . Methods : Third-year medical students received instruction on laparoscopic intracorporeal suturing and knot tying and then underwent a pretraining assessment of the task using a live porcine model . Students were then r and omized to objectives -based training on either the virtual reality ( n=8 ) or computer-enhanced ( n=8 ) training devices for 4 weeks , after which the assessment was repeated . Results : Posttraining performance had improved compared with pretraining performance in both task completion rate ( 94 % versus 18 % ; P<0.001 * ) and time [ 181±58 ( SD ) versus 292±24 * ] . Performance of the 2 groups was comparable before and after training . Of the subjects , 88 % thought that haptic cues were important in simulators . Both groups agreed that their respective training systems were effective teaching tools , but computer-enhanced device trainees were more likely to rate their training as representative of reality ( P<0.01 ) . Conclusions : Training on virtual reality and computer-enhanced devices had equivalent effects on skills improvement in novices . Despite the perception that haptic feedback is important in laparoscopic simulation training , its absence in the virtual reality device did not impede acquisition of skill Background Many laparoscopic simulation training systems exist and have been shown to transfer learning of surgical skills to the operating room . The manner in which the training is structured to maximize learning has not been examined . There are many aspects to the acquisition of laparoscopic skills during training , one of which is the availability of knowledge of results ( KR ) . Knowledge of results is information about the outcome of motor skill execution , usually provided to individuals at the end of the execution . The timing and nature of KR can affect how well people learn new motor skills . In addition , detailed instruction during learning can also affect skill acquisition . We studied the effects of KR and instruction on the learning curve of a suturing and knot-tying task . We hypothesized that KR was necessary for skill acquisition , and that detailed instruction would help trainees to learn to perform the task more correctly and reach a performance plateau earlier . In addition , the overall workload of a trainee during training would decrease as skills improved , especially when KR and coaching were provided . Methods Nine medical students with no previous laparoscopic surgical experience were r and omly and evenly divided into three groups with different KR conditions : ( 1 ) no KR , ( 2 ) KR , ( 3 ) KR + instruction . Each subject attended a training session for 1 h each day , 6 days a week for 4 consecutive weeks . Performance measures such as task time , smoothness of instrument , and path length were recorded for each trial . Workload was assessed using the NASA-TLX question naire . Results While KR was necessary for learning to suture , continual instruction had limited additional benefits . However , KR + instruction did reduce subjects ’ perceived overall workload . Conclusions Surgical training could be carried out effectively with only knowledge of results . These results have implication s for the staffing of surgical skills laboratories Background Training of skills in simulators is preferred over learning on patients so as to avoid undue injury to patients and to allow more efficient use of re sources . Most simulators are costly and require a dedicated space . The aim of this study was to evaluate a simple desktop simulator , the Mirror Trainer . Methods Thirty medical students were r and omly assigned to three groups . One group was taught laparoscopic suturing in the Mirror Trainer , the second group used a pelvic training box , while the third group served as a control group and did not receive any training . All suture attempts during training were recorded on video . A blinded , independent investigator analyzed the videos . At the completion of training , the suturing skills of each participant were evaluated in an animal model . Results Training with the Mirror Trainer required less time than with the pelvic trainer ( p < 0.001 ) . Compared with the control group , the Mirror Trainer group and the pelvic trainer group were significantly faster at creating three knots in the pig ( p = 0.001 and p = 0.004 , respectively ) . Both training groups performed equally well on the animal model ( p = 0.99 ) . Conclusion The Mirror Trainer and the pelvic trainer are equally effective in teaching laparoscopic suturing skills but training with the Mirror Trainer requires less time , can be done on any desktop , and is less costly BACKGROUND We carried out a prospect i ve , r and omized , 4-arm study including control arm , blinding of examiners to determine effectiveness of computer-based video instruction ( CBVI ) and different types of expert feedback ( concurrent and summary ) on learning of a basic technical skill . METHODS Using bench models , participants were pre-tested on a suturing and instrument knot-tying skill after viewing an instructional video . The students were subsequently assigned r and omly to 4 practice conditions : no additional intervention ( control ) , self study with CBVI , expert feedback during practice trials ( concurrent feedback ) , and expert feedback after practice trials ( summary feedback ) . All participants underwent 19 trials of practice , over 1 hour , in their assigned training condition . The effectiveness of training was assessed both at an immediate post-test and 1 month later at a retention test . Performance was evaluated using both expert-based ( Global Rating Scores ) and computer-based assessment ( H and Motion Analysis ) . Data were analyzed using repeated- measures ANOVA . RESULTS There were no differences in GRS between groups at pre-test . The CBVI , concurrent feedback and summary feedback methods were equally effective initially for the instruction of this basic technical skill to naive medical students and displayed better performance than control ( control , 12.71 [ 10.79 to 14.62 ] ; CBVI , 16.39 [ 14.38 to 18.40 ] ; concurrent , 16.97 [ 15.79 to 18.15 ] ; summary , 16.09 [ 13.57 to 18.62 ] ; P < .001 each ) . At retention . however , only CBVI and summary feedback groups retained superior suturing and knot-tying performance versus control ( control , 8.13 [ 6.94 to 9.85 ] ; CBVI , 11.92 [ 10.19 to 14.99 ] P = .037 ; concurrent , 9.80 [ 8.55 to 13.45 ] P = .635 ; summary , 111.19 [ 10.27 to 14.29 ] P = .037 ) . H and motion data displayed a similar pattern of results . There were no group differences in the rate of learning ( P > .05 ) . CONCLUSION Our study showed that CBVI can be as effective as summary expert feedback in the instruction of basic technical skills to medical students . Thoughtfully incorporated into technical curricula , CBVI can make efficient use of faculty time and serve as a useful pedagogic adjunct for basic skills training . Additionally , our study provides evidence supporting an increased role of summary feedback to effectively train novices in technical skills BACKGROUND Based on prior success of virtual-reality ( VR ) trainers in imparting surgical skills , a r and omized and controlled study was design ed to determine whether VR training improves angled-telescope operative performance . METHODS Third-year medical students received instruction on the use of an angled laparoscope and subsequently underwent performance assessment of angled telescope navigational tasks in an anesthetized porcine model . Subjects were then r and omized to objective -based training with an angled-telescope simulator ( EndoTower ; Verefi Technologies , Elizabethtown , PA ) versus no training , followed by re assessment of performance . RESULTS Initially , there were no significant differences between VR-trained ( n = 9 ) and control ( n = 10 ) groups . After training , object visualization , scope orientation , and horizon error scores were significantly better in VR-trained than control groups ; subject-matched improvement in orientation score was 50.9 % versus 10.8 % ( P < .05 ) . CONCLUSIONS VR training in angled laparoscope use improves operative performance of novices . These data support growing evidence that VR training is highly effective in improving surgical skills outside of the clinical setting TOPIC The rapid development of advanced laparoscopic techniques is a strong challenge for the skills and competence of the paediatric surgeon . It is therefore m and atory that training must offer adequate preparation . The present experimental study investigates how surgical residents perform laparoscopic bowel biopsy and defect repair after training with a pelvitrainer versus a rabbit model . METHODS New Zeal and white rabbits , 3 mm instruments , a 5 mm scope and a 6 - 0 prolene suture were used . Twelve surgical residents were r and omised into two groups . Their basic task was to take a seromuscular bowel biopsy laparoscopically and to repair the defect using an intracorporeal suture . Group I trained 8 times ( on 8 occasions ) with a pelvitrainer ( PT ) , group II trained similarly using a rabbit model ( RM ) . Each participant took a final test to demonstrate the operation in the rabbit . Operating time , suture time and perforation of the bowel were analysed . RESULTS In the PT group , mean operating times decreased from 11.18 ( + /- 5.04 ) min to 4.91 ( + /- 0.89 ) min ( p < 0.01 ) , however the final test procedure in the rabbit model lasted 9.62 ( + /- 5.11 ) min . In the RM group mean operating times also decreased from 10.04 ( + /- 3.39 ) min to 6.38 ( + /- 1.40 ) min ( p < 0.01 ) during the eight training operations . Within this group the final live operation lasted 5.45 ( + /- 0.67 ) min and was significantly faster than in the PT group 9.62 ( + /- 5.11 ) min ( p < 0.1 ) . The suture times showed a similar pattern . A significant difference with respect to the rate of perforation was not found . CONCLUSIONS Repetitive training in the rabbit provides superior skills for live operations . In paediatric surgical centres with advanced laparoscopic procedures , an animal model should be considered as an important step in training which may contribute to a beneficial outcome in patients BACKGROUND This study compares a laparoscopic skill training protocol without proficiency targets to the same protocol with explicit targets and notification of progress . METHODS Fourteen surgery interns were r and omized into 2 groups . The intervention group received task-specific proficiency criteria Output:	Comparisons between different simulation interventions ( n = 79 studies ) clarified best practice s. For example , in comparison with virtual reality , box trainers have similar effects for process skills outcomes and seem to be superior for outcomes of satisfaction and skills time . CONCLUSIONS Simulation-based laparoscopic surgery training of health professionals has large benefits when compared with no intervention and is moderately more effective than nonsimulation instruction
MS2734	*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 We conducted a r and omized study to determine whether any of three chemotherapy regimens was superior to cisplatin and paclitaxel in patients with advanced non-small-cell lung cancer . METHODS A total of 1207 patients with advanced non-small-cell lung cancer were r and omly assigned to a reference regimen of cisplatin and paclitaxel or to one of three experimental regimens : cisplatin and gemcitabine , cisplatin and docetaxel , or carboplatin and paclitaxel . RESULTS The response rate for all 1155 eligible patients was 19 percent , with a median survival of 7.9 months ( 95 percent confidence interval , 7.3 to 8.5 ) , a 1-year survival rate of 33 percent ( 95 percent confidence interval , 30 to 36 percent ) , and a 2-year survival rate of 11 percent ( 95 percent confidence interval , 8 to 12 percent ) . The response rate and survival did not differ significantly between patients assigned to receive cisplatin and paclitaxel and those assigned to receive any of the three experimental regimens . Treatment with cisplatin and gemcitabine was associated with a significantly longer time to the progression of disease than was treatment with cisplatin and paclitaxel but was more likely to cause grade 3 , 4 , or 5 renal toxicity ( in 9 percent of patients , vs. 3 percent of those treated with cisplatin plus paclitaxel ) . Patients with a performance status of 2 had a significantly lower rate of survival than did those with a performance status of 0 or 1 . CONCLUSIONS None of four chemotherapy regimens offered a significant advantage over the others in the treatment of advanced non-small-cell lung cancer PURPOSE We performed a r and omized phase II trial comparing pemetrexed with pemetrexed plus carboplatin ( PC ) in patients experiencing relapse after platinum-based chemotherapy . PATIENTS AND METHODS Main eligibility criteria were histologic or cytologic proof of advanced non-small-cell lung cancer ( NSCLC ) , relapse more than 3 months after platinum-based chemotherapy , normal organ function , and Eastern Cooperative Oncology Group performance status 0 to 2 . Patients were r and omly assigned to pemetrexed 500 mg/m(2 ) ( arm A ) or carboplatin area under the curve 5 and pemetrexed 500 mg/m(2 ) ( arm B ) , both administered intravenously every 3 weeks . Response assessment was performed every 6 weeks ; toxicity assessment was performed every 3 weeks . Primary end point was time to progression ( TTP ) ; secondary end points were objective response rate ( ORR ) , overall survival ( OS ) , and toxicity . The study was design ed to detect a 33 % decrease in the hazard of disease progression in the combination arm ( alpha = 0.05 , two-sided log-rank test ) . Polymorphisms of thymidylate synthase , the reduced folate carrier , gamma-glutamyl hydrolase , and methylenetetrahydrofolate reductase ( MTHF ) were investigated in peripheral WBCs of consenting patients . RESULTS Two hundred forty patients were enrolled . Median TTP was 2.8 months for arm A versus 4.2 months for arm B ( hazard ratio , 0.67 ; 95 % CI , 0.51 to 0.89 ; P = .005 ) . Median OS was 7.6 months and 8.0 months and ORR was 4 % and 9 % for arms A and B , respectively . Subgroup analyses found adenocarcinoma to be associated with favorable outcome . Toxicities in both arms was negligible , with one potential toxic death in arm A. Patients with MTHFR C677 T homozygous mutation had increased progression-free survival compared with patients with wild-type or heterozygous mutations ( P = .03 ) . CONCLUSION PC as second-line treatment for relapsed NSCLC result ed in a significant 33 % reduction of the hazard of disease progression as compared with pemetrexed alone BACKGROUND This is a phase II r and omized study to evaluate the efficacy and safety of bortezomib and pemetrexed alone or in combination , in patients with previously treated advanced non-small-cell lung cancer ( NSCLC ) . The primary end point was assessment of response rate . METHODS A total of 155 patients were r and omized ( 1:1:1 ) to pemetrexed ( 500mg/m(2 ) ) on day 1 plus bortezomib ( 1.6mg/m(2 ) ) on days 1 and 8 ( Arm A ) or pemetrexed ( 500mg/m(2 ) ) on day 1 ( Arm B ) or bortezomib ( 1.6mg/m(2 ) ) on days 1 and 8 ( Arm C ) of a 21 day cycle . Response rate was assessed by investigators using Response Evaluation Criteria In Solid Tumors ( RECIST ) criteria and toxicity assessed by the National Cancer Institute-Common Terminology Criteria for Adverse Events ( NCI-CTCAE ) grading system . RESULTS Response rate was 7 % in Arm A , 4 % in Arm B , and 0 % in Arm C ; disease control rates were 73 % , 62 % , and 43 % , respectively . Median overall survival was 8.6 months in Arm A , 12.7 months in Arm B , and 7.8 months in Arm C ; time to progression was 4.0 months , 2.9 months , and 1.4 months , respectively . Most common reported adverse events > /= grade 3 were neutropenia ( 19 % ) , thrombocytopenia ( 15 % ) , and dyspnea ( 13 % ) in Arm A , neutropenia ( 10 % ) in Arm B , and dyspnea ( 13 % ) and fatigue ( 10 % ) in Arm C. CONCLUSION In previously treated NSCLC the addition of bortezomib to pemetrexed was well tolerated but offered no statistically significant response or survival advantage versus pemetrexed alone , while bortezomib alone showed no clinical ly significant activity Introduction : This r and omized phase II study investigated pemetrexed in combination with the epidermal growth factor receptor (EGFR)-targeting monoclonal antibody matuzumab compared with pemetrexed alone as second-line therapy for patients with advanced non-small cell lung cancer . Methods : Patients received pemetrexed 500 mg/m2 every 3 weeks either alone ( n = 50 ) or in combination with matuzumab at either 800 mg weekly ( n = 51 ) or 1600 mg every 3 weeks ( n = 47 ) . The primary end point was objective response , as assessed by an independent review committee . Results : Tumor EGFR expression was detected in 87 % of r and omized patients . The objective response rate for the pooled matuzumab-treated arms was 11 % compared with 5 % for pemetrexed alone ( p = 0.332 ) . Apart from one patient in the pemetrexed alone group , all responses occurred in patients whose tumors expressed EGFR . The objective response rate for patients receiving weekly matuzumab was 16 % compared with 2 % for those receiving matuzumab every 3 weeks . There was also a trend for improved overall survival in patients receiving matuzumab weekly versus every 3 weeks ( 12.4 months versus 5.9 months , respectively , versus 7.9 months for pemetrexed alone ) . The combination of pemetrexed and matuzumab demonstrated an acceptable safety profile , with the most common grade 3/4 adverse event being neutropenia . Conclusion : Although the analysis on the pooled matuzumab-treated arms did not demonstrate a statistically significant improvement in objective response for the addition of matuzumab to pemetrexed compared with pemetrexed alone , the trends for improvement in objective response and overall survival for pemetrexed plus weekly matuzumab compared with pemetrexed alone warrant confirmation in additional clinical trials Introduction : We examined the efficacy of enzastaurin plus pemetrexed as second-line therapy in patients with advanced ( stage IIIA/B or IV ) non-small cell lung cancer in a double-blinded , r and omized , phase II study . Methods : Patients received pemetrexed 500 mg/m2 intravenously on day 1 of 21-day cycles ( day 8 in cycle 1 ) plus oral enzastaurin ( 250 mg two times per day ; combination arm ) or placebo ( pemetrexed arm ) . Both arms received supplementation with vitamin B12 , folic acid , and dexamethasone . An interim analysis was conducted to determine whether efficacy would warrant a phase III study . Results : The interim analysis showed no evidence of improved progression-free survival with enzastaurin . At final analysis ( N = 160 , 80 in each arm ) , baseline characteristics were well balanced . There was no significant difference in progression-free survival ( 3.0 months , p = 0.544 ) or overall survival ( 9.6 months in combination arm and 7.4 months in pemetrexed arm , p = 0.171 ) . Drug-related serious adverse events included cerebrovascular accident , palpitations , and renal failure ( n = 1 , each ) in combination arm and neutropenic sepsis , thrombocytopenia , and panniculitis ( n = 1 , each ) in pemetrexed arm . Nonhematologic drug-related grade 3/4 toxicities were similar in both arms . Grade 3/4 hematologic toxicities were higher with the combination , specifically leukopenia ( 6.3 % versus 0 % ) , neutropenia ( 15.2 % versus 5.0 % ) , and thrombocytopenia ( 8.9 % versus 1.3 % ) . Of the 26 deaths reported on- study or within 30 days of discontinuation ( 10 in combination arm and 16 in pemetrexed arm ) , none were drug related . Conclusion : The combination regimen of enzastaurin and pemetrexed is well tolerated but does not improve efficacy over pemetrexed and placebo as second-line treatment of unselected patients with advanced non-small cell lung cancer PURPOSE To compare the efficacy and toxicity of pemetrexed versus docetaxel in patients with advanced non-small-cell lung cancer ( NSCLC ) previously treated with chemotherapy . PATIENTS AND METHODS Eligible patients had a performance status 0 to 2 , previous treatment with one prior chemotherapy regimen for advanced NSCLC , and adequate organ function . Patients received pemetrexed 500 mg/m(2 ) intravenously ( i.v . ) day 1 with vitamin B(12 ) , folic acid , and dexamethasone or docetaxel 75 mg/m(2 ) i.v . day 1 with dexamethasone every 21 days . The primary end point was overall survival . RESULTS Five hundred seventy-one patients were r and omly assigned . Overall response rates were 9.1 % and 8.8 % ( analysis of variance P = .105 ) for pemetrexed and docetaxel , respectively . Median progression-free survival was 2.9 months for each arm , and median survival time was 8.3 versus 7.9 months ( P = not significant ) for pemetrexed and docetaxel , respectively . The 1-year survival rate for each arm was 29.7 % . Patients receiving docetaxel were more likely to have grade 3 or 4 neutropenia ( 40.2 % v 5.3 % ; P < .001 ) , febrile neutropenia ( 12.7 % v 1.9 % ; P < .001 ) , neutropenia with infections ( 3.3 % v 0.0 % ; P = .004 ) , hospitalizations for neutropenic fever ( 13.4 % v 1.5 % ; P < .001 ) , hospitalizations due to other drug related adverse events ( 10.5 % v 6.4 % ; P = .092 ) , use of granulocyte colony-stimulating factor support ( 19.2 % v 2.6 % , P < .001 ) and all grade alopecia ( 37.7 % v 6.4 % ; P < .001 ) compared with patients receiving pemetrexed . CONCLUSION Treatment with pemetrexed result ed in clinical ly equivalent efficacy outcomes , but with significantly fewer side effects compared with docetaxel in the second-line treatment of patients with advanced NSCLC and should be considered a st and ard treatment option for second-line NSCLC when available PURPOSE Cisplatin plus gemcitabine is a st and ard regimen for first-line treatment of advanced non-small-cell lung cancer ( NSCLC ) . Phase II studies of pemetrexed plus platinum compounds have also shown activity in this setting . PATIENTS AND METHODS This noninferiority , phase III , r and omized study compared the overall survival between treatment arms using a fixed margin method ( hazard ratio [ HR ] < 1.176 ) in 1,725 chemotherapy-naive patients with stage IIIB or IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0 to 1 . Patients received cisplatin 75 mg/m(2 ) on day 1 and gemcitabine 1,250 mg/m(2 ) on days 1 and 8 ( n = 863 ) or cisplatin 75 mg/m(2 ) and pemetrex Output:	Conclusion Pemetrexed-based doublet therapy did n’t gain any benefit in survival but significantly improved PFS and better ORR compared with single-agent pemetrexed as second-line therapy for advanced non-small-cell lung cancer . However , more incidences of grade 3 or 4 neutropenia , thrombocytopenia , and leucopenia were observed in pemetrexed-based doublet group
MS2735	*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 assess the role of etamsylate * in reducing the risk of haemorrhagic brain damage and its consequences . DESIGN Follow up of babies recruited into a r and omised controlled trial . METHODS A total of 334 infants born before 33 weeks gestation in France and Greece were r and omly allocated within the first four hours of birth either to receive etamsylate or to act as controls . The principal outcomes in the trial were death or impairment and /or disability at the age of 2 years . RESULTS Fifty nine children were lost to follow up . A total of 115 ( 34 % ) either died or had some impairment or disability , and 88 ( 26 % ) either died or had severe impairment or disability at 2 years of age . These outcomes did not differ significantly between the two r and omised groups : relative risks and 95 % confidence intervals 1.14 ( 0.78 to 1.4 ) and 1.17 ( 0.82 to 1.68 ) respectively . The findings were similar for all the prespecified subgroup analyses stratified by key prognostic factors at trial entry : country of birth , gestational age < or ⩾ 29 weeks , inborn or outborn , age < or ⩾ 1 hour , and with or without cerebral scan abnormality . CONCLUSION These findings do not support the use of etamsylate . Other strategies need to be evaluated for the prevention of mortality and morbidity in these vulnerable infants . Key messages The findings from the only published follow up of children from a r and omised controlled trial of etamsylate do not support its use when given within the first four hours of birth to infants born before 33 weeks gestation Centres in Greece and France recruited 334 infants into the trial , and did not find that etamsylate reduced the risk of haemorrhagic brain damage or its consequences in terms of death or impairment and /or disability Other strategies need to be evaluated for the prevention of mortality and morbidity in these vulnerable Cerebral blood flow velocity and cardiac output were measured with ultrasound before and 30 minutes after the administration of ethamsylate in a double blind placebo controlled study of 19 very low birthweight infants . No differences were found before or after treatment in either group Objective : To compare neurodevelopmental outcome of survivors of the multicentre trial of etamsylate ( the iRNN for ethamsylate ) for prevention of periventricular haemorrhage in very low birthweight infants . Design : Double blind , single observer , prospect i ve follow up of placebo controlled study . Setting : Six neonatal intensive care units in the United Kingdom . Neurodevelopmental outcome was assessed in health premises or children ’s homes . Subjects : 268 of 276 survivors of the original study were seen between 3.5 and 4.2 years of age . All were inborn and weighed 1500 g or less at birth . Intervention : Etamsylate 12.5 mg/kg or placebo six hourly from within one hour of delivery for four days . Main outcome measures : McCarthy scales of children ’s abilities , st and ardised neurological examination , full physical examination , functional assessment , seven letter Stycar vision test , and audiometry . Results : There was no difference between the groups in neuromotor outcome ( cerebral palsy ) or in the general cognitive index ( GCI ) of the McCarthy scales ( mean GCI was 93.3 for the etamsylate group ( n = 133 ) and 89.7 for the placebo group ( n = 131 ) ; p = 0.10 ) . There were more children with GCI < 70 ( 9 v 19 ; p = 0.047 ) or ⩽ 50 ( 3 v 11 ; p = 0.03 ) in the placebo group . Fewer children in the etamsylate group had squints ( 17 v 30 ; p = 0.042 ) or required surgery for patent ductus arteriosus ( 1 v 8 ; p = 0.036 ) . Conclusions : Etamsylate was not associated with a reduction in cerebral palsy . Severe cognitive impairment was reduced , but more children died and the improvement may be because fewer survived with low GCI The effect of Dicynene on blood loss during and after transurethral resection for benign enlargement of the prostate was studied in 76 patients . Median loss of blood at operation was 17 ml in those given Dicynene compared with 72 ml in the placebo group ( p equals less than 0.001 ) . Median postoperative blood loss was 38 ml in the Dicynene group , and 103 ml in the placebo group ( p equals 0.05 ) . Clinical evidence of deep vein thrombosis was found in neither group . Dicynene helps to reduce blood loss in transurethral resection The effectiveness of ethamsylate in the prevention of periventricular haemorrhage ( PVH ) in very low birthweight infants was evaluated by means of a multicentre , placebo-controlled , double-blind trial . In 330 infants without evidence of PVH on initial cranial ultrasound examination there was little difference between ethamsylate and placebo groups with respect to subependymal haemorrhage , but intraventricular and parenchymal haemorrhages developed in 30/162 infants ( 18.5 % ) in the treated group , compared with 50/168 ( 29.8 % ) in the control group ( p less than 0.02 ) . The incidence of intraventricular and parenchymal haemorrhage in survivors was 20/137 ( 14.6 % ) in the ethamsylate group and 37/146 ( 25.3 % ) in the controls ( p less than 0.05 ) . In 30 infants with evidence of PVH on the initial scan , ethamsylate treatment seemed to limit parenchymal extension . Analysis of the total cohort of 360 infants showed that the proportion of infants in whom an increase of two or more grade s of severity of PVH was recorded during the trial was lower in the treated than in the placebo group ( p less than 0.01 ) . No adverse effects were attributed to ethamsylate therapy . The reported incidence of patent ductus arterious was lower in the treated than in the placebo group ( p less than 0.02 ) . Mortality was similar in the two groups 22 patients complaining of primary menorrhagia or menorrhagia associated with an intrauterine device ( I.U.C.D. ) were studied in a double blind trial with crossover of ethamsylate and placebo . Acutal menstrual blood-losses were calculated from the iron content of used sanitary material during one pre-trail menstrual period and four trial menstrual periods , during which patients received ethamsylate ( " Dicynene " ) treatment during two menstrual cycles and placebo during two cycles . During ethamsylate treatment the mean menstrual blood-loss was reduced by 50 % in patients with primary menorrhagia and by 19 % in patients with an I.U.C.D. This difference between the two groups is probably accounted for by the differing values of initial blood-loss which was significantly higher in the group with primary menorrhagia . Tampon usage and the duration of bleeding were not significantly altered by ethamsylate treatment . Reported side-effects , which were not serious , were equally common during ethamsylate and placebo treatment OBJECTIVE To determine the role of ethamsylate in prevention of PVH-IVH in premature infants < 34 weeks gestational age . DESIGN Prospect i ve , r and omized , controlled study . METHODS Infants less than 34 weeks gestational age were included in the trial . Neonates with congenital malformations , family history of bleeding disorders and with Apgar scores < 5 at 5 minutes were excluded . Subjects were r and omized into two groups -- Group A infants received intravenous ethamsylate ( 12.5 mg/kg ) six hourly for four days and Group B infants served as a control group . Regular cranial ultrasounds to detect the presence of PVH-IVH were done between days 3 - 5 , 10 - 14 and 28 - 30 of post natal age , and before hospital discharge in all infants and weekly in infants detected to have PVH-IVH on earlier scans . Various antenatal and postnatal factors known to affect the incidence of PVH-IVH were recorded . RESULTS A total of 192 infants underwent the trial , 93 in Group A and 99 in Group B. Antenatal corticosteroids ( 1 or 2 doses ) were administered to 32 ( 34.4 % ) and 36 ( 36.3 % ) women in Group A and Group B , respectively . None of the mothers received phenobarbitone , vitamin K or indomethacin antenatally and none of the infants received phenobarbitone , vitamin E or indomethacin postnatally during the study period . PVH-IVH was seen in 26 infants in Group A , of which Grade I IVH occurred in 9 , Grade II in 14 , Grade III in 2 and Grade IV in one infant . Twenty-nine infants had PVH-IVH in Group B of which 11 had Grade I , 15 Grade II and 3 Grade III . None of the differences were statistically significant . CONCLUSION Postnatal administration of ethamsylate did not decrease the incidence of PVH-IVH in the study infants Some trials in premature infants with respiratory distress syndrome have shown an increased incidence of patent ductus arteriosus after exogenous surfactant therapy . The effect of prophylactic ethamsylate on patent ductus arteriosus after intratracheal administration of a single dose of porcine surfactant preparation ( Curosurf , 2.5 ml/kg ) was studied in a group of 20 preterm infants with severe respiratory distress syndrome . Gestational age of the patients was 29.2 + /- 2.5 weeks ( mean + /- SD ) , and birth weight was 1158 + /- 319 gm . Ethamsylate ( 12.5 mg/kg ) was given prophylactically within the first 4 hours of life followed by 6-hourly doses for 4 days . Hemodynamically significant patent ductus arteriosus occurred more frequently in the untreated group ( 8 of 10 ) than in the ethamsylate group ( 2 of 10 ) ( p < 0.02 ) . No acute adverse effects were attributed to the therapy . This preliminary experience suggests that ethamsylate , an inhibitor of prostagl and in bio synthesis , could be useful in reducing the incidence of patent ductus arteriosus in very low birth weight infants treated with exogenous surfactant Abstract The effect of ethamsylate , a capillary-stabilising drug , in limiting or preventing periventricular haemorrhage ( PVH ) in 70 very low birth-weight babies was evaluated in a double-blind trial . PVH developed in 9 of the 35 infants on ethamsylate and 18 of the 35 infants who received placebo . Mortality associated with PVH was similar in both groups , but the incidence of PVH of all grade s in survivors was reduced in the ethamsylate-treated group OBJECTIVES To determine whether the current incidence of intraventricular haemorrhage ( IVH ) of grade 2 or more is high enough in preterm infants born after 29 weeks gestation to justify the cost of screening with ultrasound and to explore clinical indicators for risk of IVH in the more mature preterm infant . METHODS This cohort study examined the incidence and severity of IVH in 800 preterm infants born between January 1992 and August 1996 , of whom 436 were born after 29 weeks . Demographic and clinical details were collected from a prospect ively maintained data base . The Medicare schedule charge rate for cerebral ultrasound was used to calculate costs . RESULTS 1.1 % of preterm babies born after 29 weeks gestation who had routine ultrasound scans had an IVH of grade 2 or 3 , no infant had a grade 4 IVH . Two infants had a grade 3 IVH , both of which were symptomatic . IVH was poorly predicted by other clinical criteria . Using the Medicare schedule to estimate costs , detecting the five grade 2 or 3 IVH cost A$ 42,000 . CONCLUSIONS The incidence of grade 2 - 4 IVH is low in infants born after 29 weeks gestation . Screening of this population is expensive and probably not justified . It may be most appropriate to scan these infants only if their condition raises concern Patent ductus arteriosus ( PDA ) is common in premature infants younger than 33 weeks ' gestational age ( GA ) , and its deleterious effects are increased by the presence of respiratory distress syndrome . A significant proportion of infants younger than 33 weeks ' GA have PDA . 12 Indomethacin has been used for the treatment of hemodynamically significant ductus , causing severe side effects , but even recently , it has been considered the only pharmacological approach to PDA . 3 In the early 1980s , Morgan et al 4 reported a reduction in the incidence of intraventricular hemorrhages in preterm neonates treated with ethamsylate , an inhibitor of prostagl and in bio synthesis . 4 - 6 Recently , ethamsylate has been reported to favor the closure of the ductus in preterm neonates with respiratory distress syndrome treated with exogenous surfactant . 7 In 1987 , we started prophyla Output:	There was no significant difference detected in neonatal mortality or neurodevelopmental outcome at two years between infants treated with ethamsylate and controls . There were no adverse effects of ethamsylate identified from this systematic review . Preterm infants treated with ethamsylate showed no reductions in mortality or neurodevelopmental impairment despite the reduction in any grade of intraventricular haemorrhage seen in infants < 35 weeks gestation
MS2736	*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 evaluated the effect of low-frequency rTMS on motor signs in Parkinson 's disease ( PD ) , under a double-blind placebo-controlled trial design . PD patients were r and omly assigned to received either real ( n = 9 ) or sham ( n = 9 ) rTMS for 10 days . Each session comprises two trains of 50 stimuli each delivered at 1 Hz and at 90 % of daily rest motor threshold using a large circular coil over the vertex . The effect of the stimulation , delivered during the ON-period , was evaluated during both ON and OFF periods . Tests were carried out before and after the stimulation period , and again 1 week after . The effect of the stimulation was evaluated through several gait variables ( cadence , step amplitude , velocity , the CV(stride-time ) , and the turn time ) , h and dexterity , and also the total and motor sections of the UPDRS . Only the total and motor section of the UPDRS and the turn time during gait were affected by the stimulation , the effect appearing during either ON or OFF evaluation , and most importantly , equally displayed in both real and sham group . The rest of the variables were not influenced . We conclude the protocol of stimulation used , different from most protocol s that apply larger amount of stimuli , but very similar to some previously reported to have excellent results , has no therapeutic value and should be ab and oned . This contrasts with the positive reported effects using higher frequency and focal coils . Our work also reinforces the need for sham stimulation when evaluating the therapeutic effect of rTMS OBJECTIVE Several studies have shown that repetitive transcranial magnetic stimulation ( rTMS ) over the dorsolateral prefrontal cortex ( DLPFC ) is effective in the treatment of depression in patients with Parkinson disease ( PD ) . However , since research into the effect of this type of rTMS regime on motor function is limited , we studied the effect of rTMS over the DLPFC on the motor functions in PD patients . METHODS Thirteen patients were r and omly assigned into 2 groups , one receiving real-rTMS ( 90 % of resting motor threshold , 10 Hz , 450 pulses-day for 10 consecutive days ) over the DLPFC contralateral to the more affected side , and the other group receiving sham-rTMS . Assessment included a clinical motor evaluation using part III of the Unified Parkinson 's Disease Rating Scale ( UPDRS ) , and several motor tasks . The UPDRS was applied before and after 10 days of rTMS . Finger tapping , reach movement , grip movement and gait were measured in each session before and after the rTMS over the 10 day period . RESULTS Statistical analysis ( ANOVA for repeated measures ; group * day * side * rTMS ) only showed a significant effect for finger tapping , reach movement and gait for the factor day . No significant change was reported for the UPDRS in any group . CONCLUSIONS Application of rTMS over the DLPFC as a 10 day course had no significant effect on motor functions and clinical motor status , and the improvement in performance of motor tasks can be attributed to the effects of practice . SIGNIFICANCE rTMS over the DLPFC did not lead to any motor improvement in PD patients Objective . To investigate the safety and efficacy of 50-Hz repetitive transcranial magnetic stimulation ( rTMS ) in the treatment of motor symptoms in Parkinson disease ( PD ) . Background . Progression of PD is characterized by the emergence of motor deficits that gradually respond less to dopaminergic therapy . rTMS has shown promising results in improving gait , a major cause of disability , and may provide a therapeutic alternative . Prior controlled studies suggest that an increase in stimulation frequency might enhance therapeutic efficacy . Methods . In this r and omized , double blind , sham-controlled study , the authors investigated the safety and efficacy of 50-Hz rTMS of the motor cortices in 8 sessions over 2 weeks . Assessment of safety and clinical efficacy over a 1-month period included timed tests of gait and bradykinesia , Unified Parkinson ’s Disease Rating Scale ( UPDRS ) , and additional clinical , neurophysiological , and neuropsychological parameters . In addition , the safety of 50-Hz rTMS was tested with electromyography-electroencephalogram ( EMG-EEG ) monitoring during and after stimulation . Results . The authors investigated 26 patients with mild to moderate PD : 13 received 50-Hz rTMS and 13 sham stimulation . The 50-Hz rTMS did not improve gait , bradykinesia , and global and motor UPDRS , but there appeared a short-lived “ on”-state improvement in activities of daily living ( UPDRS II ) . The 50-Hz rTMS lengthened the cortical silent period , but other neurophysiological and neuropsychological measures remained unchanged . EMG/EEG recorded no pathological increase of cortical excitability or epileptic activity . There were no adverse effects . Conclusion . It appears that 50-Hz rTMS of the motor cortices is safe , but it fails to improve motor performance and functional status in PD . Prolonged stimulation or other techniques with rTMS might be more efficacious but need to be established in future research Based on several open-label and case studies , repetitive transcranial magnetic stimulation ( rTMS ) seems to have an antidepressive effect on patients with Parkinson 's disease ( PD ) . However , this hypothesis requires further confirmation . We conducted a r and omized , double-blind placebo-controlled study to evaluate the effect of rTMS over the left dorsolateral prefrontal cortex ( DLPFC ) on depression and various motor and nonmotor features of PD . Twenty-two PD patients with mild or moderate depressive episodes were assigned into two groups , one receiving real-rTMS ( 90 % of resting motor threshold , 5 Hz , 600 pulses-a-day for 10 days ) over the left DLPFC , and another group receiving sham-rTMS . An investigator blinded to the treatment performed three video-taped examinations on each patient : before stimulation ( baseline ) , 1 day ( short term ) , and 30 days after treatment session ended ( long-term effect ) . Mini-Mental State Examination , Unified Parkinson 's Disease Rating Scale ( UPDRS ) , Hoehn-Yahr , Epworth Sleepiness , Visual Analog and Montgomery-Asberg Depression Rating Scales ( MADRS ) , Beck Depression Inventory ( BDI ) , and Trail making and Stroop tests were applied . In the actively treated group , not only depression rating scales showed significant improvement 30 days after treatment ended ( BDI by 44.4 % and MADRS by 26.1 % ) , but also the accuracy of Stroop test ( by 16 % ) . We could also demonstrate an insignificant improvement in UPDRS-III by 7.5 points ( 31.9 % , P = 0.06 ) . In the sham-treated group none of the examined tests and scales improved significantly after sham stimulation . Our study demonstrated the beneficial effect of the left DLPFC rTMS on depression in PD lasting at least 30 days after treatment . However , this result should be confirmed in patients with severe depression by further clinical trials The aim of the present study was to investigate the effects of one session of high-frequency repetitive transcranial magnetic stimulation ( rTMS ) applied over the left dorsal premotor cortex ( PMd ) and left dorsolateral prefrontal cortex ( DLPFC ) on choice reaction time in a noise-compatibility task , and cognitive functions in patients with Parkinson ’s disease ( PD ) . Clinical motor symptoms of PD were assessed as well . Ten patients with PD entered a r and omized , placebo-controlled study with a crossover design . Each patient received 10 Hz stimulation over the left PMd and DLPFC ( active stimulation sites ) and the occipital cortex ( OCC ; a control stimulation site ) in the OFF motor state , i.e. at least after 12 h of dopaminergic drugs withdrawal . Frameless stereotaxy was used to target the optimal position of the coil . For the evaluation of reaction time , we used a noise-compatibility paradigm . A short battery of neuropsychological tests was performed to evaluate executive functions , working memory , and psychomotor speed . Clinical assessment included a clinical motor evaluation using part III of the Unified Parkinson ’s Disease Rating Scale . Statistical analysis revealed no significant effect of rTMS applied over the left PMd and /or DLPFC in patients with PD in any of the measured parameters . In this study , we did not observe any effect of one session of high frequency rTMS applied over the left PMd and /or DLPFC on choice reaction time in a noise-compatibility task , cognitive functions , or motor features in patients with PD . rTMS applied over all three stimulated areas was well tolerated and safe in terms of the cognitive and motor effects Dysfunction of the basal ganglia-thalamocortical motor circuit is a fundamental model to account for motor symptoms in Parkinson 's disease ( PD ) . Using high-frequency repetitive transcranial magnetic stimulation ( rTMS ) over the supplementary motor area ( SMA ) , we investigated whether modulation of SMA excitability engenders therapeutic effects on motor symptoms in PD . In this double-blind placebo-controlled study , 99 patients were enrolled and assigned r and omly to SMA-stimulation and sham-stimulation groups . For SMA stimulation , 20 trains of 50 transcranial magnetic stimuli at 5 Hz were delivered at an intensity of 110 % active motor threshold for leg muscles in one session . The sham stimulation was 20 trains of electric stimuli given through electrodes fixed on the head to mimic the cutaneous sensation during rTMS . Each session of intervention was carried out once a week for the first 8 weeks . The SMA stimulation , in contrast to the sham stimulation , engendered significant improvements in total scores and motor scores of the Unified Parkinson 's Disease Rating Scale . Mean improvements in motor scores were 4.5 points in the SMA-stimulation group and -0.1 points in the sham-stimulation group . Results indicate that 5 Hz rTMS over SMA modestly improves motor symptoms in PD patients ; SMA is a potential stimulation site for PD treatment QUESTIONS Does the PEDro scale measure only one construct ie , the method ological quality of clinical trials ? What is the hierarchy of items of the PEDro scale from least to most adhered to ? Is there any effect of year of publication of trials on item adherence ? Are PEDro scale ordinal scores equivalent to interval data ? DESIGN Rasch analysis of two independent sample s of 100 clinical trials from the PEDro data base scored using the PEDro scale . RESULTS Both sample s of PEDro data showed fit to the Rasch model with no item misfit . The PEDro scale item hierarchy was the same in both sample s , ranging from the most adhered to item r and om allocation , to the least adhered to item therapist blinding . There was no differential item functioning by year of publication . Original PEDro ordinal scores were highly correlated with transformed PEDro interval scores ( r = 0.99 ) . CONCLUSION The PEDro scale is a valid measure of the method ological quality of clinical trials . It is valid to sum PEDro scale item scores to obtain a total score that can be treated as interval level measurement and subjected to parametric statistical analysis OBJECTIVE To assess the effects of focal motor cortex stimulation on motor performance and cortical excitability in patients with Parkinson 's disease ( PD ) . METHODS Repetitive transcranial magnetic stimulation ( rTMS ) was performed on the left motor cortical area corresponding to the right h and in 12 ' off-drug ' patients with PD . The effects of subthreshold rTMS applied at 0.5 Hz ( 600 pulses ) or at 10 Hz ( 2000 pulses ) using a ' real ' or a ' sham ' coil were compared to those obtained by a single dose of l-dopa . The assessment included a clinical evaluation by the Unified Parkinson 's Disease Rating Scale and timed motor tasks , and a neurophysiological evaluation of cortical excitability by single- and paired-pulse TMS techniques . RESULTS ' Real ' rTMS at 10 or 0.5 Hz , but not ' sham ' stimulation , improved motor performance . High-frequency rTMS decreased rigidity and bradykinesia in the upper limb contralateral to the stimulation , while low-frequency rTMS reduced upper limb rigidity bilaterally and improved walking . Concomitantly , 10 Hz rTMS increased intracortical facilitation , while 0.5 Hz rTMS restored intracortical inhibition . CONCLUSIONS Low- and high-frequency rTMS of the primary motor cortex lead to significant but differential changes in patients with PD both on clinical and electrophysiological grounds . The effects on cortical excitability were opposite to previous observations made in healthy subjects , suggesting a reversed balance of cortical excitability in patients with PD compared to normals . However , the underlying mechanisms of these changes remain to determine , as well as the relationship with clinical presentation and response to l-dopa therapy . SIGNIFICANCE The present study gives some clues to appraise the role of the primary motor cortex in PD . Clinical improvement induced by rTMS was too short-lasting to consider therapeutic application , but these results support the perspective of the primary motor cortex as a possible target for neuromodulation in PD OBJECTIVE To determine whether low-frequency repetitive transcranial magnetic stimulation ( rTMS ) may modulate l-DOPA-induced dyskinesia ( LID ) in dyskinetic Parkinson 's disease ( PD ) patients . LID is a severe motor complication in advanced PD patients . The neural mechanisms involved in LID are not clear , and it is apparent that both an excess Output:	AND RELEVANCE The pooled evidence suggests that rTMS improves motor symptoms for patients with PD . Combinations of rTMS site and frequency as well as the number of rTMS pulses are key modulators of rTMS effects .
MS2737	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To investigate the acute effects of long-term whole-body vibration on leg muscle performance and functional capacity in persons with multiple sclerosis . DESIGN A r and omized controlled trial . SUBJECTS Twenty-five patients with multiple sclerosis ( mean age 47.9 ± 1.9 years ; Exp and ed Disability Status Scale 4.3 ± 0.2 ) were assigned r and omly to whole-body vibration training ( n = 11 ) or to a control group ( n = 14 ) . METHODS The whole-body vibration group performed static and dynamic leg squats and lunges on a vibration platform ( 25 - 45 Hz , 2.5 mm amplitude ) during a 20-week training period ( 5 training sessions per 2-week cycle ) , and the control group maintained their usual lifestyle . PRE- , MID- ( 10 weeks ) and POST- ( 20 weeks ) knee-muscle maximal isometric and dynamic strength , strength endurance and speed of movement were measured using isokinetic dynamometry . Function was determined through the Berg Balance Scale , Timed Up and Go , Two-minute Walk Test and the Timed 25-Foot Walk Test . RESULTS Leg muscle performance and functional capacity were not altered following 10 or 20 weeks of whole-body vibration . CONCLUSION Under the conditions of the present study , the applied 20-week whole-body vibration exercise protocol did not improve leg muscle performance or functional capacity in mild- to moderately impaired persons with multiple sclerosis during and immediately after the training programme BACKGROUND Balance disorders are common in multiple sclerosis . AIM Aim of the study is to investigate the effectiveness of an Internet-based home training program ( e-Training ) to improve balance in patients with multiple sclerosis . DESIGN A r and omized , controlled study . SETTING Academic teaching hospital in cooperation with the therapeutic riding center Gut Üttingshof , Bad Mergentheim . POPULATION Eighteen multiple sclerosis patients ( mean EDSS 3,5 ) took part in the trial . Outcome of patients using e-Training ( N.=9 ) was compared to the outcome of patients receiving hippotherapy ( N.=9 ) , which can be considered as an advanced concept for the improvement of balance and postural control in multiple sclerosis . METHODS After simple r and om allocation patients received hippotherapy or Internet-based home training ( balance , postural control and strength training ) twice a week for 12 weeks . Assessment s were done before and after the intervention and included static and dynamic balance ( primary outcome ) . Isometric muscle strength of the knee and trunk extension/flexion ( dynamometer ) , walking capacity , fatigue and quality of life served as secondary outcome parameters . RESULTS Both intervention groups showed comparable and highly significant improvement in static and dynamic balance capacity , no difference was seen between the both intervention groups . However looking at fatigue and quality of life only the group receiving hippotherapy improved significantly . CONCLUSION Since e-Training shows even comparable effects to hippotherapy to improve balance , we believe that the established Internet-based home training program , specialized on balance and postural control training , is feasible for a balance and strength training in persons with multiple sclerosis . CLINICAL REHABILITATION IMPACT We demonstrated that Internet-based home training is possible in patients with multiple sclerosis Background Patients suffering from Multiple Sclerosis ( MS ) experience a wide array of symptoms , including balance problems , mobility impairment , fatigue and depression . Physical exercise has recently been acknowledged as a treatment option complementary to medication . However , information regarding putative effects of structured exercise programs on neurological symptoms is sparse . Tai Chi , a Chinese martial art incorporating physical exercise and mindfulness training , has been shown to yield health benefits in various neurological groups . It seems particularly suitable for patients with motoric deficits as it challenges coordination and balance . The purpose of the current study was to explore the therapeutic value of structured Tai Chi training for coordination , balance , fatigue and depression in mildly disabled MS patients . Methods A sample of 32 MS patients ( Exp and ed Disability Status Scale , EDSS < 5 ) was examined . A structured Tai Chi course was devised and a Tai Chi group participated in two weekly sessions of 90 minutes duration for six months , while a comparison group received treatment as usual ( TAU ) . Both groups were examined prior to and following the six-months interval with regards to balance and coordination performance as well as measures of fatigue , depression and life satisfaction . Results Following the intervention , the Tai Chi group showed significant , consistent improvements in balance , coordination , and depression , relative to the TAU group ( range of effect-sizes : partial η2 = 0.16 – 0.20 ) . Additionally , life satisfaction improved ( partial η2 = 0.31 ) . Fatigue deteriorated in the comparison group , whereas it remained relatively stable in the Tai Chi group ( partial η2 = 0.24 ) . Conclusions The consistent pattern of results confirms that Tai Chi holds therapeutic potential for MS patients . Further research is needed to determine underlying working mechanisms , and to verify the results in a larger sample and different MS subgroups Background Multiple Sclerosis ( MS ) is a disease of the central nervous system that results in many symptoms including mobility limitation and fatigue . Patients and Methods Thirty-one MS patients , all female with mean of age of 36.75 years and Exp and ed Disability Status Scale scores ( EDSS ) of 1.0 to 4.0 were recruited . Subjects were r and omly assigned to one of the three groups : treadmill training , yoga or control groups . Treadmill training and yoga practice consisted of 8 weeks ( 24 sessions , thrice weekly ) . The control group followed their own routine treatment program . Balance , speed and endurance of walking , fatigue , depression and anxiety were measured by Berg Balance scores , time for 10 m walk and distance for a two minute walk , Fatigue Severity Scale ( FFS ) , Beck Depression Inventory ( BDI ) and Beck Anxiety Inventory ( BAI ) , respectively . Results Comparison of results have shown that pre- and post- interventions produced significant improvements in the balance score , walking endurance , FFS score , BDI score and BAI score in the treadmill training group and yoga group . However , 10 m walk time decreased in the treadmill training group but did not show any clear change in the yoga group . Moreover , the analysis showed significant differences between the treadmill training group and yoga group for BAI score . Conclusions These results suggest that treadmill training and yoga practice improved ambulatory function , fatigue and mood status in the individuals with mild to moderate MS Objective : The primary aim was to investigate the comparative effects of massage therapy and exercise therapy on patients with multiple sclerosis . The secondary aim was to investigate whether combination of both massage and exercise has an additive effect . Design : R and omized controlled pilot trial with repeated measurements and blinded assessment s. Setting : Local Multiple Sclerosis Society . Subjects : A total of 48 patients with multiple sclerosis were r and omly assigned to four equal subgroups labelled as massage therapy , exercise therapy , combined massage – exercise therapy and control group . Interventions : The treatment group received 15 sessions of supervised intervention for five weeks . The massage therapy group received a st and ard Swedish massage . The exercise therapy group was given a combined set of strength , stretch , endurance and balance exercises . Patients in the massage – exercise therapy received a combined set of massage and exercise treatments . Patients in the control group were asked to continue their st and ard medical care . Main measures : Pain , fatigue , spasticity , balance , gait and quality of life were assessed before and after intervention . Results : Massage therapy result ed in significantly larger improvement in pain reduction ( mean change 2.75 points , P = 0.001 ) , dynamic balance ( mean change , 3.69 seconds , P = 0.009 ) and walking speed ( mean change , 7.84 seconds , P = 0.007 ) than exercise therapy . Patients involved in the combined massage – exercise therapy showed significantly larger improvement in pain reduction than those in the exercise therapy ( mean change , 1.67 points , P = 0.001 ) . Conclusions : Massage therapy could be more effective than exercise therapy . Moreover , the combination of massage and exercise therapy may be a little more effective than exercise therapy alone Background : Resistance training studies in multiple sclerosis ( MS ) often use short intervention periods . Furthermore , training efficiency could be optimized by unilateral training and /or electrical stimulation . Objective : To examine the effect(s ) of unilateral long-term ( 20 weeks ) st and ardized resistance training with and without simultaneous electro-stimulation on leg muscle strength and overall functional mobility . Methods : A r and omized controlled trial involving 36 persons with MS . At baseline ( PRE ) and after 10 ( MID ) and 20 ( POST ) weeks of st and ardized ( ACSM ) light to moderately intense unilateral leg resistance training ( RESO , n = 11 ) only or resistance training with simultaneous electro-stimulation ( RESE , n = 11 , 100 Hz , biphasic symmetrical wave , 400 µs ) , maximal isometric strength of the knee extensors and flexors ( 45 ° , 90 ° knee angle ) and dynamic ( 60–180 ° /s ) knee-extensor strength was measured and compared with a control group ( CON , n = 14 ) . Functional mobility was evaluated using the Timed Get Up and Go , Timed 25 Foot Walk , Two-Minute Walk Test , Functional Reach and Rivermead Mobility Index . Results : Maximal isometric knee extensor ( 90 ° , MID : + 10 ± 3 % , POST : + 10 ± 4 % ) in RESO and knee flexor ( 45 ° , POST : + 7 ± 4 % ; 90 ° , POST : + 9 ± 5 % ) in RESE strength increased ( p < 0.05 ) compared with CON but RESO and RESE did not differ . Also , impaired legs responded positively to resistance training ( unilateral leg strength analysis ) and functional reaching increased significantly in RESO ( + 18 % ) compared with CON . Dynamic muscle strength and the remaining functional mobility tests did not change . Conclusion : Long-term light to moderately intense resistance training improves muscle strength in persons with MS but simultaneous electro-stimulation does not further improve training outcome BACKGROUND People with Multiple Sclerosis ( PwMS ) are less physically active than the general population and pragmatic approaches design ed to equip them with the skills and confidence to participate in long-term physical activity are required . OBJECTIVE The objective of this study was to determine the feasibility of a pragmatic exercise intervention in PwMS . METHODS A voluntary sample of 30 PwMS ( male n = 4 , female n = 26 ; mean age = 40 years ; range = 24 - 49 years ) , with mild to moderate disability ( EDSS ≤ 5.5 ) , were recruited from eligible participants attending outpatient clinics . A total of 28 participants were r and omised to a 10 week pragmatic exercise intervention ( 2 × supervised and 1 × home-based session per week ) or usual care . Clinical , functional and quality of life ( MSQoL-54 ) outcomes were assessed at baseline , immediately and 3 months after the intervention . RESULTS Attrition was low ( 2 participants lost to immediate follow-up and 4 participants lost to 3 month follow-up ) , with high compliance rates ( > 75 % of all sessions ) . The intervention group achieved progression of exercise volume ( 24.3 ± 7.0 to 30.9 ± 5.5 min per session ) , intensity ( 60.4 ± 8.8 to 67.7 ± 6.9 % HR max ) and training impulse ( min × average HR = training impulse/load [ arbitrary units ; AU ] ) ( 2600 ± 1105 to 3210 ± 1269AU ) during the intervention , whilst significantly increasing(P = 0.050 ) their physical composite score ( MSQOL-54 ) at 10 weeks and readiness to exercise ( P = 0.003 ) at 3 months compared with usual care . CONCLUSION This pragmatic intervention was feasible for PwMS , but further research is needed to assess its long-term impact on physical activity behaviour Background : Extensive research on both healthy subjects and patients with central nervous damage has eluci date d a crucial role of postural adjustment reactions and central sensory integration processes in generating and “ shaping ” locomotor function , respectively . Whether robotic-assisted gait devices might improve these functions in Multiple sclerosis ( MS ) patients is not fully investigated in literature . Purpose : The aim of this study was to compare the effectiveness of end-effector robot-assisted gait training ( RAGT ) and sensory integration balance training ( SIBT ) in improving walking and balance performance in patients with MS . Methods : Twenty-two patients with MS ( EDSS : 1.5–6.5 ) were r and omly assigned to two groups . The RAGT group ( n = 12 ) underwent end-effector system training . The SIBT group ( n = 10 ) underwent specific balance exercises . Each patient received twelve 50-min treatment sessions ( 2 days/week ) . A blinded rater evaluated patients before and after treatment as well as 1 month post treatment . Primary outcomes were walking speed and Berg Balance Scale . Secondary outcomes were the Activities-specific Balance Confidence Scale , Sensory Organization Balance Test , Stabilometric Assessment , Fatigue Severity Scale , cadence , step length , single and double support time , Multiple Sclerosis Quality of Life-54 . Results : Between groups comparisons showed no significant differences on primary and secondary outcome measures over time . Within group comparisons showed significant improvements in both groups on the Berg Balance Scale ( P = 0.001 ) . Changes approaching significance were found on gait speed ( P = 0.07 ) only in the Output:	Given the number of MS relapses reported for the exercise condition ( N = 25 ) and non-exercise control condition ( N = 26 ) , exercise does not seem to be associated with a significant risk of a MS relapse . However , in general , MS relapses were defined and reported poorly . Exercise therapy can be prescribed in people with MS without harm . Exercise therapy , and particularly endurance , mixed , or ' other ' training , may reduce self reported fatigue .
MS2738	*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 Little is known about the efficacy of " next step " strategies for patients with post-traumatic stress disorder ( PTSD ) who remain symptomatic despite treatment . This study prospect ively examines the relative efficacy of augmentation of continued prolonged exposure therapy ( PE ) with paroxetine CR versus placebo for individuals remaining symptomatic despite a course of PE . METHOD Adult out patients meeting DSM-IV criteria for PTSD were recruited from February 2003 to September 2005 at 4 academic centers . Phase I consisted of 8 sessions of individual PE over a 4- to 6-week period . Participants who remained symptomatic , defined as a score of > or= 6 on the Short PTSD Rating Interview ( SPRINT ) and a Clinical Global Impressions-Severity of Illness scale ( CGI-S ) score > or= 3 , were r and omly assigned to the addition of paroxetine CR or matched placebo to an additional 5 sessions of PE ( Phase II ) . RESULTS Consistent with prior studies , the 44 Phase I completers improved significantly with initial PE ( SPRINT : paired t = 7.6 , df = 41 , p < .0001 ; CGI-S : paired t = 6.37 , df = 41 , p < .0001 ) . Counter to our hypothesis , however , we found no additive benefit of augmentation of continued PE with paroxetine CR compared to pill placebo for the 23 r and omly assigned patients , with relatively minimal further gains overall in Phase II . CONCLUSION Although replication with larger sample s is needed before definitive conclusions can be drawn , our data do not support the addition of paroxetine CR compared with placebo to continued PE for individuals with PTSD who remain symptomatic after initial PE , suggesting that the development of novel treatment approaches for PTSD refractory to PE is needed . CLINICAL TRIALS REGISTRATION Clinical Trials.gov identifier NCT00215163 To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrolment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results OBJECTIVE To examine the potential benefits of adding a selective serotonin reuptake inhibitor , sertraline , versus placebo , to trauma-focused cognitive-behavioral therapy ( TF-CBT ) for improving posttraumatic stress disorder and related psychological symptoms in children who have experienced sexual abuse . METHOD Twenty-four 10- to 17-year-old female children and adolescents and their primary caretakers were r and omly assigned to receive TF-CBT + sertraline or TF-CBT + placebo for 12 weeks . RESULTS Both groups experienced significant improvement in posttraumatic stress disorder and other clinical outcomes from pre- to posttreatment with no significant group x time differences between groups except in Child Global Assessment Scale ratings , which favored the TF-CBT + sertraline group . CONCLUSIONS Only minimal evidence suggests a benefit to adding sertraline to TF-CBT . A drawback of adding sertraline was determining whether TF-CBT or sertraline caused clinical improvement for children with comorbid depression . Current evidence therefore supports an initial trial of TF-CBT or other evidence -supported psychotherapy for most children with PTSD symptoms before adding medication We examined the feasibility , acceptability , and therapeutic efficacy of a culturally adapted cognitive – behavior therapy ( CBT ) for twelve Vietnamese refugees with treatment-resistant posttraumatic stress disorder ( PTSD ) and panic attacks . These patients were treated in two separate cohorts of six with staggered onset of treatment . Repeated measures Group × Time ANOVAs and between-group comparisons indicated significant improvements , with large effect sizes ( Cohen 's d ) for all outcome measures : Harvard Trauma Question naire ( HTQ ; d=2.5 ) ; Anxiety Sensitivity Index ( ASI ; d=4.3 ) ; Hopkins Symptom Checklist-25 ( HSCL-25 ) , anxiety subscale ( d=2.2 ) ; and Hopkins Symptom Checklist-25 , depression subscale ( d=2.0 ) scores . Likewise , the severity of ( culturally related ) headache- and orthostasis-cued panic attacks improved significantly across Background : To date , there have been no studies comparing cognitive behavior therapy ( CBT ) with Rogerian therapy in post-traumatic stress disorder . Method : Sixty out patients with DSM-IV chronic post-traumatic stress disorder were r and omized into two groups for 16 weekly individual sessions of CBT or Rogerian supportive therapy ( ST ) at two centers . No medication was prescribed . Measures included the Post-Traumatic Stress Disorder Checklist Scale ( PCLS ) , the Hamilton Anxiety Scale , Beck Depression Inventory , and Quality of Life . The general criterion of improvement ( GCI ) was a score of less than 44 on the PCLS . Results : Forty-two patients were evaluated at post-test , 38 at week 52 and 25 at week 104 . At post-test , the rate of patients leaving the trial due to worsening or lack of effectiveness was significantly higher in the ST group ( p = 0.004 ) . At this point , no between-group difference was found on the GCI and any of the rating scales . Intent-to-treat analysis found no difference for the GCI , but patients in the CBT group showed greater improvement on the PCLS and Hamilton Anxiety Scale . Naturalistic follow-up showed sustained improvement without between-group differences at weeks 52 and 104 . Conclusions : CBT retained significantly more patients in treatment than ST , but its effects were equivalent to those of ST in the completers . CBT was better in the dimensional intent-to-treat analysis at post-test Abstract This study evaluated the benefits of add-on hypnotherapy in patients with chronic PTSD . Thirty-two PTSD patients treated by SSRI antidepressants and supportive psychotherapy were r and omized to 2 groups : 15 patients in the first group received Zolpidem 10 mg nightly for 14 nights , and 17 patients in the hypnotherapy group were treated by symptom-oriented hypnotherapy , twice-a-week 1.5-hour sessions for 2 weeks . All patients completed the Stanford Hypnotic Susceptibility Scale , Form C , Beck Depression Inventory , Impact of Event Scale , and Visual Subjective Sleep Quality Question naire before and after treatment . There was a significant main effect of the hypnotherapy treatment with PTSD symptoms as measured by the Posttraumatic Disorder Scale . This effect was preserved at follow-up 1 month later . Additional benefits for the hypnotherapy group were decreases in intrusion and avoidance reactions and improvement in all sleep variables assessed The present study was design ed to determine whether augmenting sertraline with prolonged exposure ( PE ) would result in greater improvement than continuation with sertraline alone . Outpatient men and women with chronic PTSD completed 10 weeks of open label sertraline and then were r and omly assigned to five additional weeks of sertraline alone ( n = 31 ) or sertraline plus 10 sessions of twice-weekly PE ( n = 34 ) . Results indicated that sertraline led to a significant reduction in PTSD severity after 10 weeks but was associated with no further reductions after five more weeks . Participants who received PE showed further reduction in PTSD severity . This augmentation effect was observed only for participants who showed a partial response to medication OBJECTIVE The relative short-term efficacy and long-term benefits of pharmacologic versus psychotherapeutic interventions have not been studied for posttraumatic stress disorder ( PTSD ) . This study compared the efficacy of a selective serotonin reup-take inhibitor ( SSRI ) , fluoxetine , with a psychotherapeutic treatment , eye movement desensitization and reprocessing ( EMDR ) , and pill placebo and measured maintenance of treatment gains at 6-month follow-up . METHOD Eighty-eight PTSD subjects diagnosed according to DSM-IV criteria were r and omly assigned to EMDR , fluoxetine , or pill placebo . They received 8 weeks of treatment and were assessed by blind raters posttreatment and at 6-month follow-up . The primary outcome measure was the Clinician-Administered PTSD Scale , DSM-IV version , and the secondary outcome measure was the Beck Depression Inventory-II . The study ran from July 2000 through July 2003 . RESULTS The psychotherapy intervention was more successful than pharmacotherapy in achieving sustained reductions in PTSD and depression symptoms , but this benefit accrued primarily for adult-onset trauma survivors . At 6-month follow-up , 75.0 % of adult-onset versus 33.3 % of child-onset trauma subjects receiving EMDR achieved asymptomatic end-state functioning compared with none in the fluoxetine group . For most childhood-onset trauma patients , neither treatment produced complete symptom remission . CONCLUSIONS This study supports the efficacy of brief EMDR treatment to produce substantial and sustained reduction of PTSD and depression in most victims of adult-onset trauma . It suggests a role for SSRIs as a reliable first-line intervention to achieve moderate symptom relief for adult victims of childhood-onset trauma . Future research should assess the impact of lengthier intervention , combination treatments , and treatment sequencing on the resolution of PTSD in adults with childhood-onset trauma Concentration camp survivors from Bosnia-Herzegovina , now refugees in the Netherl and s , were given early outpatient treatment for posttraumatic stress disorder ( PTSD ) for 6 months . They were tested with the Watson Question naire before entering therapy , after 6 months and 3 years later when a structured interview design ed to obtain information on psychosocial status was administered . Data were analyzed with PCA-STAT 1.1 statistical package . The treatment was effective on a short-term basis with some long-term effects . Elderly people were no more vulnerable to the onset of PTSD than younger ones but were more resistant to therapy . Psychosocial factors had neither protective nor risk value for the development of PTSD in this group The purpose of this experiment was to conduct a dismantling study of cognitive processing therapy in which the full protocol was compared with its constituent components -- cognitive therapy only ( CPT-C ) and written accounts (WA)--for the treatment of posttraumatic stress disorder ( PTSD ) and comorbid symptoms . The intent-to-treat ( ITT ) sample included 150 adult women with PTSD who were r and omized into 1 of the 3 conditions . Each condition consisted of 2 hr of therapy per week for 6 weeks ; blind assessment s were conducted before treatment , 2 weeks following the last session , and 6 months following treatment . Measures of PTSD and depression were collected weekly to examine the course of recovery during treatment as well as before and after treatment . Secondary measures assessed anxiety , anger , shame , guilt , and dysfunctional cognitions . Independent ratings of adherence and competence were also conducted . Analyses with the ITT sample and with study completers indicate that patients in all 3 treatments improved substantially on PTSD and depression , the primary measures , and improved on other indices of adjustment . However , there were significant group differences in symptom reduction during the course of treatment whereby the CPT-C condition reported greater improvement in PTSD than the WA condition There has been growing interest in the concept of resilience and the question as to whether psychotropic medications or psychosocial treatments might have resilience-enhancing effects . This pilot study investigates resilience in a sample of patients with post-traumatic stress disorder ( PTSD ) before and after treatment . Effects of treatment with tiagabine , fluoxetine , sertraline alone , and sertraline with cognitive behavioural therapy on resilience were assessed using the Connor-Davidson Resilience Scale ( CD-RISC ) . Changes in resilience after treatment were measured and response to treatment was predicted from demographic , resilience and baseline disability measures . Changes in resilience following treatment were statistically significant . Items that showed the greatest change related to confidence , control , coping , knowing where to turn for help and adaptability . Items showing the least change related to religious and existential aspects of resiliency , effort , acting on a hunch , decision-making and goals . In linear and logistic regression models , gender , baseline CD-RISC score , baseline Sheehan Disability Scale score and an individual item from the CD-RISC scale , ‘ Sense of Humor ’ , were significant predictors of response to treatment . Treatment of PTSD significantly improved resilience and reduced symptoms in this sample . Further controlled studies are Output:	There is not enough evidence available to support or refute the effectiveness of combined psychological therapy and pharmacotherapy compared to either of these interventions alone .
MS2739	*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 study presents the immediate post-intervention results of Kids and Adults Now - Defeat Obesity ! , a r and omized controlled trial to enhance healthy lifestyle behaviors in mother-preschooler ( 2 - 5 years old ) dyads in North Carolina ( 2007 - 2011 ) . The outcomes include change from baseline in the child 's diet , physical activity and weight , and in the mother 's parenting behaviors , diet , physical activity , and weight . METHOD The intervention targeted parenting through maternal emotion regulation , home environment , feeding practice s , and modeling of healthy behaviors . 400 mother-child dyads were r and omized . RESULTS Mothers in the intervention arm , compared to the control arm , reduced instrumental feeding ( -0.24 vs. 0.01 , p<0.001 ) and TV snacks ( -.069 vs. -0.24 , p=0.001 ) . There were also improvements in emotional feeding ( p=0.03 ) , mother 's sugary beverage ( p=0.03 ) and fruit/vegetable ( p=0.04 ) intake , and dinners eaten in front of TV ( p=0.01 ) ; these differences were not significant after adjustment for multiple comparisons . CONCLUSION KAN-DO , design ed to maximize the capacity of mothers as agents of change , improved several channels of maternal influence . There were no group differences in the primary outcomes , but differences were observed in the parenting and maternal outcomes and there were trends toward improvement in the preschoolers ' diets . Long-term follow-up will address whether these short-term trends ultimately improve weight status Objective To assess the effect of a governmentally-led center based child care physical activity program ( Youp’là Bouge ) on child motor skills . Patients and methods We conducted a single blinded cluster r and omized controlled trial in 58 Swiss child care centers . Centers were r and omly selected and 1:1 assigned to a control or intervention group . The intervention lasted from September 2009 to June 2010 and included training of the educators , adaptation of the child care built environment , parental involvement and daily physical activity . Motor skill was the primary outcome and body mass index ( BMI ) , physical activity and quality of life secondary outcomes . The intervention implementation was also assessed . Results At baseline , 648 children present on the motor test day were included ( age 3.3 ± 0.6 , BMI 16.3 ± 1.3 kg/m2 , 13.2 % overweight , 49 % girls ) and 313 received the intervention . Relative to children in the control group ( n = 201 ) , children in the intervention group ( n = 187 ) showed no significant increase in motor skills ( delta of mean change ( 95 % confidence interval : -0.2 ( −0.8 to 0.3 ) , p = 0.43 ) or in any of the secondary outcomes . Not all child care centers implemented all the intervention components . Within the intervention group , several predictors were positively associated with trial outcomes : 1 ) free-access to a movement space and parental information session for motor skills 2 ) highly motivated and trained educators for BMI 3 ) free-access to a movement space and purchase of mobile equipment for physical activity ( all p < 0.05 ) . Conclusion This “ real-life ” physical activity program in child care centers confirms the complexity of implementing an intervention outside a study setting and identified potentially relevant predictors that could improve future programs . Trial registration Clinical trials.gov Context : Recent data indicate a marked increase in the prevalence of obesity among school-aged children . Thus , efficacious programmes that prevent overweight development in children are urgently needed . Objective : To evaluate the impact of repeatedly given , individualised dietary and lifestyle counselling on the prevalence of overweight during the first 10 years of life . Design and participants : This study was a part of the Special Turku Coronary Risk Factor Intervention Project for Children ( STRIP ) , which is a prospect i ve , r and omised trial aim ed at reducing the exposure of the intervention children to the known risk factors of atherosclerosis . At the child 's age of 7 months , 1062 children were assigned to an intervention group ( n=540 ) or to a control group ( n=522 ) . The intervention children received individualised counselling focused on healthy diet and physical activity biannually . Height and weight of the children were measured at least once a year . Main outcome measure : Prevalence of overweight and obesity among the intervention and control children by sex and age . Children were classified as overweight or obese if their weight for height was > 20 % or ⩾40 % above the mean weight for height of healthy Finnish children , respectively . Results : After the age of 2 years , there were continuously fewer overweight girls in the intervention group than in the control group . At the age of 10 years , 10.2 % of the intervention girls and 18.8 % of the control girls were overweight ( P=0.0439 ) , whereas 11.6 % of the intervention boys and 12.1 % of the control boys were overweight ( P≈1.00 ) . Only three children in the intervention group were obese at some age point , whereas 14 control children were classified as obese at some age point . Conclusion : Individualised dietary and lifestyle counselling given twice a year since infancy decreases prevalence of overweight in school-aged girls even without any primary energy restrictions OBJECTIVE The purpose of the present study was to evaluate the effects of a school-based , 2-year , multi-component intervention on BMI , eating and physical activity behaviour in Fl and ers , Belgium , targeting children aged 3 - 6 years in communities of high and low socio-economic status ( SES ) . DESIGN Cluster-r and omized controlled trial . SETTING Thirty-one pre- primary and primary schools in three different intervention communities and three paired-matched ( on SES profile ) control communities in Fl and ers , Belgium . SUBJECTS BMI Z-scores at baseline and follow-up were calculated for 1102 children . Question naires with sociodemographic data and FFQ were available from 694 of these 1102 children . RESULTS No significant effects were found on BMI Z-scores for the total sample . However , there was a significant decrease in BMI Z-score of 0·11 in the low-SES intervention community compared with the low-SES control community , where the BMI Z-score increased by 0·04 ( F = 6·26 , P = 0·01 ) . No significant intervention effects could be found for eating behaviour , physical activity or screen-time . There were no significant interaction effects of age and gender of the children on the outcome variables . CONCLUSIONS Although no significant effects were found for BMI Z-scores in the total sample , this intervention had a promising effect in the low-SES community of reducing excess weight gain among young children OBJECTIVE To evaluate the impact of nutrition education in kindergartens and to promote healthy dietary habits in children . DESIGN Prospect i ve cohort study . Four kindergartens with 1252 children were r and omized to the intervention group and three with 850 children to the control group . The personal nutritional knowledge , attitudes and dietary behaviours of the parents were also investigated . Each month , children and parents in the intervention group participated in nutrition education activities . The main outcome measures were anthropometrics and diet-related behaviours of the children and the nutritional knowledge and attitudes of the parents at baseline , 6 months ( mid-term ) and 1 year ( post-test ) . Baseline demographic and socio-economic characteristics were also collected . SETTING Seven kindergartens from Hefei , the capital city of Anhui Province , eastern China . SUBJECTS Two thous and one hundred and two 4- to 6-year-old pre-schoolers from seven kindergartens participated . RESULTS The prevalence of children 's unhealthy diet-related behaviours decreased significantly and good lifestyle behaviours increased in the group receiving nutrition education compared with controls . Parental eating habits and attitudes to planning their children 's diets also changed appreciably in the intervention group compared with the control group ( P < 0.05 ) . However , there were no statistically significant differences in children 's height , weight , height-for-age Z-score or weight-for-age Z-score between the two groups . CONCLUSIONS Kindergarten-based nutrition education improves pre-schoolers ' lifestyle behaviours and brings about beneficial changes in parents ' attitudes to planning their children 's diets and their own personal eating habits OBJECTIVE The aim of the present study was to evaluate the effects of a 1-year family-based healthy lifestyle intervention implemented through day-care centres on toddlers ' BMI Z-scores and reported activity- and dietary-related behaviours . DESIGN Pilot cluster-r and omized controlled trial . SETTING Seventy child-care centres in three different intervention communities and three paired-matched control communities in Fl and ers , Belgium . SUBJECTS A sample of 203 Belgian toddlers aged 9 - 24 months was included in the study . Objective ly assessed weight and height were used to calculate BMI Z-scores . A parental-report question naire was used to assess children 's lifestyle behaviours . RESULTS Positive intervention effects were found on BMI Z-score . No intervention effects were found for activity- and dietary-related behaviours targeted by the intervention . In both intervention and control groups , daily consumption of water , soft drinks , sweets and savoury snacks increased while daily consumption of fruit and vegetables decreased over 1 year . Daily physical activity remained stable but screen-time behaviour increased in both groups over time . CONCLUSIONS The study showed that a family-based healthy lifestyle intervention implemented through day-care centres can lead to healthier weight outcomes in toddlers . In both groups , an unhealthier lifestyle pattern was observed over 1 year which underlines the importance of the early childhood period as the focus of future behavioural interventions OBJECTIVE To evaluate the impact of a school-based health behavior intervention known as Planet Health on obesity among boys and girls in grade s 6 to 8 . DESIGN R and omized , controlled field trial with 5 intervention and 5 control schools . Outcomes were assessed using preintervention ( fall 1995 ) and follow-up measures ( spring 1997 ) , including prevalence , incidence , and remission of obesity . PARTICIPANTS A group of 1295 ethnically diverse grade 6 and 7 students from public schools in 4 Massachusetts communities . INTERVENTION Students participated in a school-based interdisciplinary intervention over 2 school years . Planet Health sessions were included within existing curricula using classroom teachers in 4 major subjects and physical education . Sessions focused on decreasing television viewing , decreasing consumption of high-fat foods , increasing fruit and vegetable intake , and increasing moderate and vigorous physical activity . MAIN OUTCOME MEASURES Obesity was defined as a composite indicator based on both a body mass index and a triceps skinfold value greater than or equal to age- and sex-specific 85th percentiles . Because schools were r and omized , rather than students , the generalized estimating equation method was used to adjust for individual-level covariates under cluster r and omization . RESULTS The prevalence of obesity among girls in intervention schools was reduced compared with controls , controlling for baseline obesity ( odds ratio , 0.47 ; 95 % confidence interval , 0.24 - 0.93 ; P = .03 ) , with no differences found among boys . There was greater remission of obesity among intervention girls vs. control girls ( odds ratio , 2.16 ; 95 % confidence interval , 1.07 - 4.35 ; P = .04 ) . The intervention reduced television hours among both girls and boys , and increased fruit and vegetable consumption and result ed in a smaller increment in total energy intake among girls . Reductions in television viewing predicted obesity change and mediated the intervention effect . Among girls , each hour of reduction in television viewing predicted reduced obesity prevalence ( odds ratio , 0.85 ; 95 % confidence interval , 0.75 - 0.97 ; P = .02 ) . CONCLUSION Planet Health decreased obesity among female students , indicating a promising school-based approach to reducing obesity among youth The aim of this study was to assess the feasibility , acceptability and potential efficacy of a physical activity program for preschool children . A 20-week , 2-arm parallel cluster r and omized controlled pilot trial was conducted . The intervention comprised structured activities for children and professional development for staff . The control group participated in usual care activities , which included design ated inside and outside playtime . Primary outcomes were movement skill development and objective ly measured physical activity . At follow-up , compared with children in the control group , children in the intervention group showed greater improvements in movement skill proficiency , with this improvement statically significant for overall movement skill development ( adjust diff . = 2.08 , 95 % CI 0.76 , 3.40 ; Cohen 's d = 0.47 ) and significantly greater increases in objective ly measured physical activity ( counts per minute ) during the preschool day ( adjust diff . = 110.5 , 95 % CI 33.6 , 187.3 ; Cohen 's d = 0.46 ) . This study demonstrates that a physical activity program implemented by staff within a preschool setting is feasible , acceptable and potentially efficacious OBJECTIVE To prospect ively examine the effects of a r and omized school-based intervention on nutrition and physical activity knowledge and preferences , anthropometric measures , and fitness in low socioeconomic kindergarten children . STUDY DESIGN A total of 376 children completed a school-year combined dietary-behavioral-physical activity intervention and were compared with 349 control subjects ( age 3.8 to 6.8 years ) . RESULT Output:	Thus , there was a lack of evidence for physical activity interventions during peri-conception and pregnancy . Interventions with evidence of efficacy tended to target multiple levels of the SEM , with emphasis on parents , and extend over long periods . Effective intervention elements for early life obesity prevention included classes on parenting skills , alteration of the kindergarten playground , and financial incentives . Evidence from low- and middle-income countries was scarce , and evidence for intervention effect on obesity-related NCDs was missing .
MS2740	*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 current study was design ed to explore the use of behavioral ( i.e. , accuracy and reaction times ) and electrophysiological measures ( i.e. , event-related potentials ) to assess the impact of a family-based preventive intervention for preschool-aged , maltreated children in foster care . These measures were recorded during a computerized flanker task design ed to assess cognitive control and response monitoring . The sample was recruited from a larger r and omized efficacy trial of Multidimensional Treatment Foster Care for Preschoolers ( MTFC-P ) and included foster children assigned to the intervention condition ( n = 10 ) , foster children assigned to a services-as-usual comparison condition ( n = 13 ) , and low-income , nonmaltreated community children ( n = 11 ) . The children ’s behavioral and electrophysiological performance on the task was generally consistent with previous research with adults and older children . There were no group differences on the behavioral measures of cognitive control or response monitoring . Notably , however , group differences were observed on the electrophysiological measures of response monitoring . Specifically , the foster children who received services as usual were significantly less responsive to performance feedback about errors than the foster children who received the intervention and the nonmaltreated children . Applications of this methodology and implication s of the results for future prevention research are discussed Children with language processing deficits have various learning impairments and poor scholastic performance . In 3 - 10 % of all children a specific language processing deficit can be identified by the Sound Connecting Sub-Test of the Illinois Test of Psycholinguistic-Abilities ( SC-ITPA ) . These children among which we drew our index group ( AS-Group ) suffer from the disability to recognize isolated sounds as parts of words . Following linguistic terminology this is known as an auditory sequential sound processing deficit ( ASSPD ) Eighteen children ( AS-Group ) and 21 controls ( C-Group ) were subjected to mapped P300 evoked potential analyses of cortical response to acoustic stimulation in the oddball paradigm . The data presented here show that there exists significant relation between the P300 amplitude reduction and ASSPD . The P300 amplitude decrease measured in the AS-Group is due to a reduced information transmission in accordance with Johnson 's Triarchic Model of the P300 Amplitude . The cerebral structures involved in poor language processing are localized at the left temporo-parietal cortex . This supports the hypothesis that the underlying neuronal defect of ASSPD is localized in the language center and not in the auditory pathway . The P300 amplitude may serve as electrophysiological tool to identify ASSPD and to quantify the degree of improvement in the course of specific therapy The magnocellular deficit theory is one of the prominent hypotheses in dyslexia research . However , recent studies have produced conflicting results . Ten dyslexic children and 12 controls were examined with visual evoked potentials elicited by r and om dot kinematogram . The experiment comprises two sequences , one with r and omly moving dots ( control condition ) and a second sequence where a fraction of the dots were moved coherently at the left or right side ( depending on the level of coherence , 10 % , 20 % , and 40 % of the dots ) . R and omly moving dots elicited two components , a P100 and P200 , which were not different between the groups . Coherently moving dots elicited a late positivity between 300 and 800 ms , which was significantly attenuated in dyslexic children . The area of this component becomes larger at a higher level of coherence . This study supports the hypothesis of an impairment of a specific magnocellular function in dyslexia PURPOSE To verify the effectiveness of the Cognitive Auditory Evoked Potential-P300 ( CAEP-P300 ) for monitoring the therapeutical evolution of students with developmental dyslexia . METHODS Twenty students diagnosed with developmental dyslexia , of both genders , aged between 8 and 14 years , divided into two r and omized groups , one of them su bmi tted to a phonological remediation program associated with reading and writing ( GI ) , and the other one representing the control group ( GII ) , participated in the study . The groups were paired up , and the individuals were su bmi tted to two evaluations of the CAEP-P300 and the same interval was kept for both . Paired Student 's t-test , ANOVA test , and Pearson 's correlation coefficient were used , adopting 5 % significance level . RESULTS The statistical comparison of the pre and post evaluations of each group demonstrated difference in the Phonological Awareness Test ( p=0.000 ) and in the P300 latency ( p=0.005 ) only for GI . CONCLUSION CAEP-P300 use for monitoring the therapeutical evolution of children with developmental dyslexia is possible and represents a viable option for intervention programs PURPOSE To evaluate whether a hypothesis suggesting that apraxia of speech results from phonological overspecification could be relevant for childhood apraxia of speech ( CAS ) . METHOD High-density EEG was recorded from 5 children with CAS and 5 matched controls , ages 5 - 8 years , with and without CAS , as they listened to r and omized sequences of CV syllables in two oddball paradigms : phonemic ( /ba/ , /pa/ ) and allophonic ( /pa/ , /p(h)a/ ) . RESULTS In the phonemic contrast condition , mismatch negativity ( MMN ) responses to oddball sounds were observed for the typically developing ( comparison ) group but not the CAS group , although a component similar to an immature mismatch response was apparent . The allophonic contrast did not elicit MMN responses in the comparison group , but in the CAS group , an MMN-like response was observed . CONCLUSION The authors propose that these preliminary findings are consistent with a view of CAS as a disorder that not only affects motor planning but also has a phonological component Output:	The present meta- analysis demonstrates that speech therapy does not influence the latency and amplitude results of the P300 evoked potential in children undergoing speech therapy intervention
MS2741	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: INTRODUCTION The South Pacific has a high prevalence of obesity and super-obesity . We review ed our experience with laparoscopic sleeve gastrectomy ( LSG ) to evaluate its efficacy and safety . METHODS A retrospective review of a prospect ively collected data base of LSGs carried out by one surgeon in one center . The percentage of excess weight loss and the rate of resolution or improvement of comorbidities reflected efficacy , and major complications or mortalities reflected safety . RESULTS From January 2008 to February 2013 , we performed 510 surgeries and included 494 consecutive patients ( 367 females ) ( 45.5 ± 11.2 years ) in our study . LSG was the primary procedure in 384 patients , 6 patients had redo bariatric surgery after failure of initial LSG , 57 patients had a history of gastric b and ing with insufficient weight loss or b and -related complications , and 46 super-obese patients had an intragastric balloon placed before LSG . Average starting body mass index was 47.8 kg m(-2 ) . Mean percent excess weight loss was 64.3 % at 1 year ; 67.3 % at 2 years and 66.4 % at 3 years . The percentages of resolved comorbidities were as follows : hypertension : 48.3 % , type 2 diabetes mellitus : 72.5 % , dyslipidemia : 61.0 % , and obstructive sleep apnea : 77.8 % . The mortality rate was 1/494 . The postoperative morbidity included gastric fistula in 3.0 % , hemorrhaging in 2.4 % , and postoperative gastroesophageal reflux in 9.4 % . CONCLUSIONS In the South Pacific , LSG is a safe and effective means of treating morbid obesity with sustained weight loss and resolution of comorbid medical conditions Background Laparoscopic sleeve gastrectomy ( LSG ) is emerging as a popular “ st and -alone ” bariatric procedure . We report our 5 years experience with LSG as a single-stage bariatric procedure with which to study the technical progress , learning curve , complications , and follow-up results . Methods Prospect ively collected data of 228 patients ( 145 females and 83 males ) , who underwent LSG for morbid obesity , from February 2007 to March 2012 , was retrospectively analyzed . Results The mean age was 34.68 years ( range , 18–62 years ) and the mean preoperative body mass index ( BMI ) was 37.42 ± 4.75 kg/m2 ( range , 32.08–65.69 kg/m2 ) . Mean operative time was 60.63 ± 27.37 min . The mean BMI decreased to 26.15 ± 3.71 kg/m2 at 3 years ( p < 0.001 ) and to 27.94 ± 4.08 kg/m2 at 5 years ( p < 0.001 ) . Mean percentage excess weight loss was 71.96 ± 21.30 % at 3 years and 63.71 ± 20.08 % at 5 years . The 30-day readmission rate was 3.07 % .Overall complication rate was 4.3 % , including strictures , leaks , peritonitis , gastrocutaneous fistula , and one ( 0.43 % ) mortality . One patient with weight regain and another with stricture underwent conversion to Roux-en-Y gastric bypass . Complication rates significantly decreased after the first 50 cases ( p = 0.022 ) , suggesting an initial learning curve . Resolution of diabetes , hypertension , and hyperlipidemia was 66.67 , 100 , and 50 % , respectively , at 5 years . Conclusions LSG as a single-stage bariatric procedure is safe and durable , achieving weight loss and resolution of comorbidities up to 5 years . Adherence to technical details is pivotal in reducing complications associated with the initial learning phase BACKGROUND Bariatric surgery is considered as being contraindicated for morbidly obese patients who also have inflammatory bowel disease ( IBD ) . The aim of our study was to report the outcomes of bariatric surgery in morbidly obese IBD patients . METHODS The prospect ively collected data of all the patients diagnosed as having IBD who underwent bariatric operations in 2 medical centers between October 2006 and January 2014 were retrieved and analyzed . RESULTS One male and 9 female morbidly obese IBD patients ( 8 with Crohn 's disease and 2 with ulcerative colitis ) underwent bariatric surgery . Their mean age was 40 years , and their mean body mass index was 42.6 kg/m2 . Nine of them underwent a laparoscopic sleeve gastrectomy and 1 underwent a laparoscopic adjustable gastric b and . Eight patients had obesity-related co-morbidities , including type 2 diabetes , hypertension , sleep apnea , osteoarthropathy , etc . After a median follow-up of 46 months ( range 9 - 67 ) , all of the patients lost weight , with an excess weight loss of 71 % , and 10 out of 16 obesity-related co-morbidities were resolved . There was 1 complication not related to IBD , and no IBD exacerbation . CONCLUSION Bariatric surgery was safe and effective in our morbidly obese IBD patients . The surgical outcome in this selected patient group was similar to that of comparable non-IBD patients Introduction : Laparoscopic sleeve gastrectomy ( LSG ) is gaining acceptance as a st and -alone bariatric procedure with proven efficacy on weight loss and obesity-related comorbidities . A specific and potentially severe complication of LSG is the staple line leak ( SLL ) . Our aim was to report the SLL rate and its management in a prospect i ve cohort of 378 LSGs . Patients and Methods : A total of 378 patients underwent LSG from July 2005 to July 2011 . The gastric transection was performed by an initial 60 mm firing of 4.5 mm staples at the antrum and successive 60 mm firings of 3.5 mm staples at the gastric body and fundus toward the left diaphragmatic crus . A 36 Fr bougie was used to calibrate the gastric tube . The staple line was systematic ally reinforced with a partial-thickness running suture . Results : The overall complications and SLL rate were 20/378 ( 5.29 % ) and 9/378 ( 2.38 % ) , respectively . SLLs were managed by laparoscopic ( n=2 ) or open ( n=1 ) exploration , drainage and endoscopic self-exp and able covered stent , computed tomography – guided percutaneous drainage ( n=2 ) , or a self-exp and able covered stent alone ( n=4 ) . Medical support including total parenteral nutrition and adapted antibiotics was started in all patients . The combined treatment modalities were successful in all cases . Conclusions : SLL was the most common complication of LSG accounting for half of the overall complications . Percutaneous drainage and self-covered stents combined with antibiotics and parenteral nutrition are effective for SLL and should be proposed as first-line treatment in stable patients Background Single incision laparoscopy remains controversial due to technical challenges which may cause suboptimal outcomes . This study aims to evaluate the feasibility and equivalency of the single incision sleeve gastrectomy ( SISG ) when compared to the traditional multiport sleeve gastrectomy ( MPSG ) approach in a matched cohort evaluating technical aspects and postoperative results . Methods This is a retrospective analysis of prospect ively collected data in a consecutive cohort of 113 SG ( MPSG = 77 , SISG = 36 ) . The 36 patients who underwent SISG were included as the case group . Thirty-six MPSG patients were included in the control group , in 1:1 ratio with cases after matching for BMI , age , race , gender , and additional demographic data . Operative time ( OT ) in minutes and length of stay ( LOS ) in days was measured and excess weight loss ( EWL ) at 6 months and 1 year was collected and evaluated . Results Mean BMI was equivalent ( SISG 43.06 , MPSG 43.72 , p = 0.36 ) . Mean OT for the SISG was 116.78 and 118.25 for the MPSG ( p = 0.84 ) , and mean LOS was 1.80 for the SISG and 1.75 for the MSPG ( p = 0.75 ) . EWL at 6 months was 58.4 % for the SISG and 58.5 % for the MPSG ( p = 0.98 ) and 72.3 and 74.1 % ( p = 0.77 ) for 1 year , respectively . There were no leaks in either group . There was one reoperation for postoperative bleeding in the MPSG group . Conclusions Sleeve gastrectomy can be performed safely using single incision techniques with equivalent outcomes for weight loss Background One of the most serious complications after laparoscopic sleeve gastrectomy ( LSG ) is gastric leak . Few publications exist concerning the treatment of gastric leak . We sought to determine by way of a prospect i ve study the clinical presentation , postoperative course , and treatment of gastric leak after LSG for obesity . Methods From October 2005 to August 2008 , 214 patients with different degrees of obesity underwent LSG . During surgery , each patient received saline with methylene blue by way of nasogastric tube and had a drain placed . All patients underwent radiologic study with liquid barium sulphate on postoperative day 3 . Results Seven patients developed gastric leak . Leak in two patients ( 28.6 % ) was diagnosed by upper gastrointestinal tract ( UGI ) study . Two patients had type I leak ( 28.6 % ) , and five patients had type II leak ( 71.4 % ) . Four patients underwent reoperation . Three patients were managed medically with enteral or parenteral feeding ; the drain was maintained in situ ; and collection s were drained by percutaneous punctions guided by computed axial tomography . Mean hospital length of stay was 28.8 days , and time to leakage closure was 43 days after surgery . Conclusion Different ways exist to manage gastric leak , depending on the magnitude of the collection and the clinical repercussions . When treatment necessitates reintervention and is performed early , suture repair is more likely to be successful . Leakage closure time will vary Background Bariatric operations mostly combine a restrictive gastric component with a rerouting of the intestinal passage . The pylorus can thereby be alternatively preserved or excluded . With the aim of performing a “ pylorus-preserving gastric bypass ” , we present early results of a proximal postpyloric loop duodeno-jejunostomy associated with a sleeve gastrectomy ( LSG ) compared to results of a parallel , but distal LSG with a loop duodeno-ileostomy as a two-step procedure . Methods 16 patients underwent either a two-step LSG with a distal loop duodeno-ileostomy ( DIOS ) as revisional bariatric surgery or a combined single step operation with a proximal duodeno-jejunostomy ( DJOS ) . Total small intestinal length was determined to account for inter-individual differences . Results Mean operative time for the second-step of the DIOS operation was 121 min and 147 min for the combined DJOS operation . The overall intestinal length was 750.8 cm ( range 600 - 900 cm ) with a bypassed limb length of 235.7 cm in DJOS patients . The mean length of the common channel in DIOS patients measured 245.6 cm . Overall excess weight loss ( % EWL ) of the two-step DIOS procedure came to 38.31 % and 49.60 % , DJOS patients experienced an % EWL of 19.75 % and 46.53 % at 1 and 6 months , resp . No complication related to the duodeno-enterostomy occurred . Conclusions Loop duodeno-enterosomies with sleeve gastrectomy can be safely performed and may open new alternatives in bariatric surgery with the possibility for inter-individual adaptation Background To evaluate changes in obesity-related diseases and micronutrients after laparoscopic sleeve gastrectomy ( LSG ) . Methods We started the procedure in May 2007 , and by December 2011 , 117 patients could be evaluated for a two year follow-up . Comparisons of preoperative status with 12 and 24 months postoperative status were made for body mass index ( BMI ) , obesity-related diseases and micronutrients . Results Major complications included bleeding requiring transfusion at 5.1 % , leak at 1.7 % and abscess without a visible leak at 0.9 % . Mean BMI was reduced from 46.6 ( st and ard deviation ( SD ) 6.0 ) kg/m2 to 30.6 ( SD 5.6 ) kg/m2 at two years , and resolution occurred for 80.7 % of patients with type 2 diabetes , 63.9 % with hypertension , 75.8 % with hyperlipidemia , 93.0 % with sleep apnea Output:	Conclusions This systematic review of staple-line leaks following LSG demonstrated a significantly lower rate using APM staple-line reinforcement as compared to oversewing , use of sealants , BPS reinforcement , or no reinforcement . Variation in surgical technique may also contribute to leak rates
MS2742	*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 evaluated the influence of maternal pre-pregnancy body mass index ( BMI ) , based on reported pre-pregnancy weight and height , on blood pressure ( BP ) levels during pregnancy by using information from a prospect i ve cohort of 1733 women recruited before 20 weeks ' gestation . Maternal antenatal BP values were abstract ed from medical records , and we evaluated the mean BP differences according to BMI group in regression models , using generalised estimating equations to account for repeated BP records within each pregnancy . In each trimester , mean systolic BP ( SBP ) and diastolic BP ( DBP ) values were positively associated with maternal pre-gestational BMI . This association persisted after adjustment for maternal age , parity , smoking , education , marital status and physical activity . Overweight women ( 25 - 29 kg/m(2 ) ) had first- , second- and third-trimester mean SBPs that were 8.1 , 7.7 and 8.2 mmHg , respectively , higher than values observed in lean women ( < 20 kg/m(2 ) ) . Mean DBP values were 4.5 , 5.4 and 5.6 mmHg higher for each successive trimester in overweight vs. lean women . Obese ( > 30 kg/m(2 ) ) women consistently had the highest mean SBP and DBP values . Trimester-specific mean SBP values were 10.7 - 12.0 mmHg higher among obese women vs. lean women . Corresponding trimester-specific mean DBP values were 6.9 - 7.4 mmHg higher in obese vs. lean women . Similar patterns were observed when trimester-specific average mean arterial pressures were evaluated . Elevated pregnancy BPs associated with maternal pre-gestational BMI are consistent with a large body of literature that documents increased pre-eclampsia risk among overweight and obese women Objective : To establish the profiles of 24-h non-invasive ambulatory blood pressure measurement ( ABPM ) during the trimesters of pregnancy and the puerperium in normotensive healthy primigravidae Design : A prospect i ve study in which 24-h ABPM was performed on five occasions in each subject : in the first trimester between 9 and 16 weeks ' gestation ; in the second trimester between 18 and 24 weeks ; in the third trimester between 26 and 32 weeks and between 33 and 40 weeks ; and finally at 6 weeks post partum Method : One hundred and six Caucasian primigravid women who were normotensive at their first booking visit were recruited consecutively from the antenatal clinic and had 24-h ABPM performed with the SpaceLabs 90207 ambulatory system Results : Of the 106 women recruited , 98 completed 24-h ABPM on four of the five measurement occasions . Four women delivered prematurely before 33 weeks ' gestation , thereby missing one ABPM measurement . Changes during pregnancy and the puerperium were assessed against the ABPM performed in the first trimester . There was no difference for daytime or night-time systolic blood pressure between 9 and 33 weeks , but it rose significantly from 33 to 40 weeks . At 6 weeks post partum , systolic blood pressure was not significantly different from the daytime pressure in the first-trimester ABPM but was raised significantly at night . Diastolic blood pressure decreased significantly between 18 and 24 weeks for both daytime and night-time . From 33 to 40 weeks it increased in parallel with systolic blood pressure , and at 6 weeks post partum it was raised significantly compared with first-trimester values for daytime and night-time . The nocturnal fall in blood pressure was preserved throughout pregnancy with a significant difference between daytime and night-time measurements present on all measurement occasions for systolic , diastolic and mean blood pressures and heart rate . There were significant differences between daytime ABPM and clinic blood pressure for both systolic and diastolic blood pressure up to 33 weeks . From 33 weeks until 6 weeks post partum there was no significant difference between daytime ambulatory and clinic blood pressures Conclusion : This study provides reference values for ABPM in healthy primigravidae with generally uncomplicated Objective : To study longitudinally changes in blood pressure ( BP ) and heart rate ( HR ) during healthy pregnancies and to evaluate the influence of parity , pregestational overweight , and excessive weight gain . Methods : A prospect i ve longitudinal cohort study of 57 healthy white women with singleton pregnancies . BP and HR were measured repeatedly at gestational age 14–16 weeks , 22–24 weeks , 30–32 weeks , 36 weeks , and 6 months postpartum using both an oscillometric measurement device ( Dinamap ) and finger arterial pressure ( Finometer PRO ) . Results : SBP , DBP , and mean arterial pressure ( MAP ) reached a statistically significant trough at gestational age 22–24 weeks using both measurement devices . When compared with the nonpregnant measurement , SBP at gestational age 22–24 weeks was 6.2 mmHg [ 95 % confidence interval ( 95 % CI ) 1.3–11.2 ] lower measured by Finometer and 7.2 mmHg ( 95 % CI 4.2–10.1 ) lower measured by Dinamap . DBP and MAP were 8.9 mmHg ( 95 % CI 4.6–13.2 ) and 9.8 mmHg ( 95 % CI 5.3–14.2 ) lower measured by Finometer . Measured by Dinamap , DBP and MAP were 4.5 mmHg ( 95 % CI 1.7–7.3 ) and 5.4 mmHg ( 95 % CI 2.8–7.9 ) lower at gestational age 22–24 weeks when compared with the nonpregnant state . SBP was significantly higher in women with pregestational BMI at least 25 kg/m2 with both measurement devices ( both P < 0.05 ) . There were no differences in SBP , DBP , or MAP depending on parity or excessive weight gain . Conclusion : BP measured repeatedly by two different noninvasive devices during pregnancy and postpartum showed a statistically significant drop in mid-pregnancy , followed by a progressive increase until term Background Pregnancy associated cardiovascular pathologies have a significant impact on outcome for mother and child . Bioimpedance cardiography may provide additional outcome -relevant information early in pregnancy and may also be used as a predictive instrument for pregnancy-associated diseases . Methods We performed a prospect i ve longitudinal cohort trial in an outpatient setting and included 242 pregnant women . Cardiac output and concomitant hemodynamic data were recorded from 11th–13th week of gestation every 5th week as well as at two occasions post partum employing bioimpedance cardiography . Results Cardiac output increased during pregnancy and peaked early in the third trimester . A higher heart rate and a decreased systemic vascular resistance were accountable for the observed changes . Women who had a pregnancy-associated disease during a previous pregnancy or developed hypertension or preeclampsia had a significantly increased cardiac output early in pregnancy . Furthermore , an effect of cardiac output on birthweight was found in healthy pregnancies and could be confirmed with multiple linear regression analysis . Conclusions Cardiovascular adaptation during pregnancy is characterized by distinct pattern described herein . These may be altered in women at risk for preeclampsia or reduced birthweigth . The assessment of cardiac parameters by bioimpedance cardiography could be performed at low costs without additional risks STUDY QUESTION Are there differences in preconception cardiovascular function between women who have a viable pregnancy and those who have a first trimester miscarriage ? SUMMARY ANSWER Preconception cardiovascular function of central haemodynamics and arterial function are similar between women who have a viable pregnancy and those who have a first trimester miscarriage . WHAT IS KNOWN ALREADY Miscarriages have been associated with increased long-term cardiovascular disease risk , and arterial and cardiovascular dysfunction has been hypothesised as the common link . It is not known if these risks are present prior to pregnancy or are a reflection of poor arterial and haemodynamic adaptation to pregnancy . STUDY DESIGN , SIZE , DURATION This prospect i ve longitudinal preconception cohort study was conducted over 18 months . In total , 367 participants were recruited pre-pregnancy , from which 197 pregnancies were recorded ; 39 of these pregnancies ended in first trimester miscarriage . Complete longitudinal data were available for 172 pregnancies ( 140 viable pregnancies , 32 first trimester miscarriages ) from pre-pregnancy to 6 weeks gestation . PARTICIPANTS / MATERIAL S , SETTING , METHODS This was a single site study based at a maternity hospital in London . Healthy women were recruited prior to natural conception and followed up once they became pregnant . All underwent haemodynamic [ cardiac output ( CO ) , peripheral vascular resistance ( PVR ) ] and arterial function [ aortic augmentation index ( AIx ) and pulse wave velocity ( PWV ) ] testing prior to pregnancy and at 6 weeks gestation , using non-invasive devices ( gas re-breathing method , Innocor ® and an occilometric device , Vicorder ® ) . Cross-sectional measurements at pre-pregnancy and 6 weeks gestation and a longitudinal analysis of changes were compared between women who had a subsequent viable pregnancy , and those who had a subsequent first trimester miscarriage . MAIN RESULTS AND THE ROLE OF CHANCE There were no differences between women destined to have a healthy ongoing pregnancy compared to those who miscarried , in terms of baseline cardiovascular function , assessed by CO , PVR , PWV or AIx . Similarly , between the groups , there were no differences in pregnancy adaptation with similar trends in cardiovascular function changes from pre-pregnancy to 6 weeks gestation . LIMITATIONS , REASONS FOR CAUTION Whilst this is the first study to investigate preconception and early pregnancy haemodynamic and arterial function in relation to viability , the relatively modest number of miscarriages may not be sufficient to show subtle differences in haemodynamic changes if these were present . WIDER IMPLICATION S OF THE FINDINGS This study suggests that pre-pregnancy haemodynamic and arterial function is unlikely to be the causal link between miscarriages and future cardiovascular disease . Our findings suggests that factors other than the presence of a viable embryo drive cardiovascular changes in early pregnancy . This study raises new questions about miscarriages as an independent risk event which predisposes women to increased cardiovascular risk later in life . STUDY FUNDING /COMPETING INTEREST(S ) The investigators are funded by NIHR Imperial BRC , NIHR Cambridge BRC , Action Medical Research , Imperial College Healthcare Charity and Tommy 's Charity . We acknowledge the loan of ultrasound equipment from Samsung Medison ( South Korea)/MIS Ltd and provision of fertility monitors from SPD Development Company Ltd ( Bedford , UK ) . There are no competing interests . C.C.L. is supported by the UK National Institute for Health Research Biomedical Research Centre based at Imperial College Healthcare National Health Service Trust and Imperial College London . TRIAL REGISTRATION NUMBER Objective : To extend findings that African American women report greater stress during pregnancy , have higher blood pressure ( BP ) , and are twice as likely to have low birthweight infants relative to white women . This study examines a ) racial differences in associations between stress and BP during pregnancy , and b ) the combined effects of stress and BP on infant birthweight in a sample of 170 African American and white women . Methods : A prospect i ve , longitudinal study of pregnant women was conducted in which measures of BP , stress , and other relevant variables were collected . Multiple measures of systolic and diastolic BP were taken at each of three points during pregnancy ( 18–20 , 24–26 , and 30–32 weeks gestation ) . Results : Both systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) were positively associated with stress in pregnant African American women and not in pregnant white women . In analyses of birthweight , there were no main effects of BP or stress . However , a significant interaction demonstrated that , when stress was high , DBP was negatively associated with birthweight and a combination of high stress and high DBP predicted the lowest birthweight in the sample . Furthermore , African American women were twice as likely as white women to have a combination of high stress and high DBP . Conclusions : Racial differences in relationships between stress and BP , and the interactive effect of stress and DBP on birthweight together suggest that a high stress-high BP profile may pose a risk for lower birthweight among African American women , in particular , and possibly for all pregnant women . BP = blood pressure ; DBP = diastolic blood pressure ; SBP = systolic blood pressure ; BMI = body mass index ; Ms = means Abstract This article evaluates the association of hepatic , renal , and inflammatory biomarkers with changes in systolic ( SBP ) and diastolic ( DBP ) blood pressure ( BP ) during healthy pregnancies . A prospect i ve cohort study with 225 healthy pregnant women was conducted in Rio de Janeiro , Brazil . SBP and DBP were evaluated throughout pregnancy ( 5th–13th , 20th–26th , and 30th–36th gestational weeks ) and were the outcomes . The following biomarkers were measured at the first trimester and analyzed according to tertiles of the sample distribution and were considered the main independent predictors : alkaline phosphatase ( ALP ) , alanine aminotransferase ( ALT ) , aspartate aminotransferase ( A Output:	Including only higher- quality studies had little effect on findings , with heterogeneity remaining high ( I2 statistic > 50 % ) . Significant gestational blood pressure and heart rate changes occur that should be taken into account when assessing pregnant women . Commonly taught substantial decreases in blood pressure mid-pregnancy were not seen and heart rate increases were lower than previously thought .
MS2743	*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 evaluated the effects of a 6-month combined aerobic and resistance training program on the body composition , glycemic control , lipid profile , and functional capacity of older patients with a long history of type 2 diabetes . 25 subjects ( 65.9 ± 4 . 2 yrs ; M/F : 13/12 ) with a long history of type 2 diabetes ( 16.7 ± 6.7 yrs ) were r and omly allocated into either the exercise or control groups . The exercise group trained three sessions a week . Each session consisted of a warm-up period , 30 minutes of moderate aerobic exercise , 10 minutes of resistance training with five leg muscle exercises ( two sets of 10 - 12 repetitions at 50 - 70 % of 1RM for each activity ) , and a cool-down period . The variables of body composition , glycemic control , lipid profile , and functional capacity were measured before and after the study period . Exercise training decreased waist-hip ratio and body fat of the trained subjects . Concentrations of fasting and 2-hour post-glucose challenge plasma glucose and serum insulin , and glycosylated hemoglobin decreased significantly in the exercise group . Exercise training improved the lipid profile and also increased the leg muscle strength and 6-minute walking distance of the trained subjects . The control group , however , increased their body fat and fasting plasma glucose , while other variables were not changed during the study period . The current results demonstrate that elderly patients with a long history of type 2 diabetes can benefit from the 6-month combined aerobic and resistance training program . Key pointsExercise training is effective for elderly patients with long-term type 2 diabetesExercise prescription for elderly patients with type 2 diabetes should contain both aerobic and resistance activities PURPOSE The aim of this study was to determine the effects of Tai Chi exercise on glucose control , neuropathy scores , balance , and quality of life in patients with type 2 diabetes and neuropathy . METHODS A pretest-posttest design with a nonequivalent control group was utilized to recruit 59 diabetic patients with neuropathy from an outpatient clinic of a university hospital . A st and ardized Tai Chi for diabetes program was provided , which comprised 1 hour of Tai Chi per session , twice a week for 12 weeks . Outcome variables were fasting blood glucose and glycosylated hemoglobin for glucose control , the Semmes-Weinstein 10-g monofilament examination scores and total symptom scores for neuropathy , single leg stance for balance , and the Korean version of the SF-36v2 for quality of life . Thirty-nine patients completed the posttest measures after the 12-week Tai Chi intervention , giving a 34 % dropout rate . RESULTS The mean age of the participants was 64 years , and they had been diagnosed with type 2 diabetes for more than 12 years . The status was significantly better for the participants in the Tai Chi group ( n=20 ) than for their control ( i.e. , nonintervention ) counterparts ( n=19 ) in terms of total symptom scores , glucose control , balance , and quality of life . CONCLUSION Tai Chi improved glucose control , balance , neuropathic symptoms , and some dimensions of quality of life in diabetic patients with neuropathy . Further studies with larger sample s and long-term follow-up are needed to confirm the effects of Tai Chi on the management of diabetic neuropathy , which may have an impact on fall prevention in this population OBJECTIVE This study assessed the effects of balance/strength training on falls risk and posture in older individuals with type 2 diabetes . RESEARCH DESIGN AND METHODS Sixteen individuals with type 2 diabetes and 21 age-matched control subjects ( aged 50–75 years ) participated . Postural stability and falls risk was assessed before and after a 6-week exercise program . RESULTS Diabetic individuals had significantly higher falls risk score compared with control subjects . The diabetic group also exhibited evidence of mild-to-moderate neuropathy , slower reaction times , and increased postural sway . Following exercise , the diabetic group showed significant improvements in leg strength , faster reaction times , decreased sway , and , consequently , reduced falls risk . CONCLUSIONS Older individuals with diabetes had impaired balance , slower reactions , and consequently a higher falls risk than age-matched control subjects . However , all these variables improved after resistance/balance training . Together these results demonstrate that structured exercise has wide-spread positive effects on physiological function for older individuals with type 2 diabetes BACKGROUND Strength training has been shown to be beneficial in older adults . However , very little data exist on the effects of strength training in older diabetics . METHODS 31 community-dwelling older adults with diabetes ( mean age = 66.1 years ) were r and omly assigned to either an exercise ( EX ) or control ( CO ) group . The EX group trained the plantar flexors , knee extensors , knee flexors , hip extensors , and hip flexors muscle groups at 50 % , 60 % , and 70 % of 1-repetition maximum , 2.6 days a week , for 24 months . Mobility tests included the timed up and go , 50-foot walk , and walking up and down 8 stairs . Strength and mobility for both groups were evaluated at 6-month intervals . RESULTS There was a group and time effect as the EX group increased 31.4 % ( p < .001 ) in strength for all muscle groups after the first 6 months of training , and the strength gains were retained for the duration of the training intervention . There was also a group and time effect for mobility as performance increased 8.6 % and 9.8 % ( p = .032 and p = 0.031 ) for the first 6 and 12 months , respectively , but decreased to 4.6 % above baseline at the end of the intervention . There were essentially no changes from baseline strength or mobility values for the CO group . CONCLUSION In conclusion , these data suggest that a moderate-intensity resistive-training program can improve mobility and strength for the duration of a 24-month intervention in older adults with diabetes , thus potentially reducing the rate of mobility loss during aging Background Interventions for preventing falls in older people often involve several components , multidisciplinary teams , and implementation in a variety of setting s. We have developed a classification system ( taxonomy ) to describe interventions used to prevent falls in older people , with the aim of improving the design and reporting of clinical trials of fall-prevention interventions , and synthesis of evidence from these trials . Methods Thirty three international experts in falls prevention and health services research participated in a series of meetings to develop consensus . Robust techniques were used including literature review s , expert presentations , and structured consensus workshops moderated by experienced facilitators . The taxonomy was refined using an international test panel of five health care practitioners . We assessed the chance corrected agreement of the final version by comparing taxonomy completion for 10 r and omly selected published papers describing a variety of fall-prevention interventions . Results The taxonomy consists of four domains , summarized as the " Approach " , " Base " , " Components " and " Descriptors " of an intervention . Sub-domains include ; where participants are identified ; the theoretical approach of the intervention ; clinical targeting criteria ; details on assessment s ; descriptions of the nature and intensity of interventions . Chance corrected agreement of the final version of the taxonomy was good to excellent for all items . Further independent evaluation of the taxonomy is required . Conclusions The taxonomy is a useful instrument for characterizing a broad range of interventions used in falls prevention . Investigators are encouraged to use the taxonomy to report their interventions Background . Peak oxygen uptake ( VO2peak ) and muscle function are more decreased in patients with a combination of chronic heart failure ( CHF ) and type 2 diabetes mellitus ( 2DM ) compared to patients with only one of the conditions . Further , patients with 2DM have peripheral complications that hamper many types of conventional exercises . Aim . To evaluate the efficacy and applicability of eight-week aquatic exercise in patients with the combination of CHF and 2DM . Methods . Twenty patients ( four women ) with both CHF and 2DM ( age 67.4 ± 7.1 , NYHA II-III ) were r and omly assigned to either aquatic exercise or a control group . The patients exercised for 45 minutes 3 times/week in 33–34 ° C , swimming pool . Results . The training programme was well tolerated . Work rate ( + 11.7 ± 6.6 versus −6.4 ± 8.1 watt , P < 0.001 ) and VO2peak ( + 2.1 ± 0.8 versus −0.9 ± 1.4 mL·kg−1·min−1 , P < 0.001 ) and walking capacity ( P = 0.01 ) increased significantly in the training group . Muscle function was also significantly improved and Hba1c decreased significantly ( P < 0.01 ) during training , while fasting glucose , insulin , c-peptide , and lipids were unchanged . Training also increased vitality measured by SF-36 significantly ( P = 0.05 ) . Conclusion . Aquatic exercise could be used to improve exercise capacity and muscle function in patients with the combination of CHF and 2DM Hispanics are at increased risk of morbidity and mortality due to their high prevalence of diabetes and poor glycemic control . Strength training is the most effective lifestyle intervention to increase muscle mass but limited data is available in older adults with diabetes . We determined the influence of strength training on muscle quality ( strength per unit of muscle mass ) , skeletal muscle fiber hypertrophy , and metabolic control including insulin resistance ( Homeostasis Model Assessment –HOMA-IR ) , C-Reactive Protein ( CRP ) , adiponectin and Free Fatty Acid ( FFA ) levels in Hispanic older adults . Sixty-two community-dwelling Hispanics ( > 55 y ) with type 2 diabetes were r and omized to 16 weeks of strength training plus st and ard care ( ST group ) or st and ard care alone ( CON group ) . Skeletal muscle biopsies and biochemical measures were taken at baseline and 16 weeks . The ST group show improved muscle quality ( mean±SE : 28±3 ) vs CON ( -4±2 , p<0.001 ) and increased type I ( 860±252µm2 ) and type II fiber cross-sectional area ( 720±285µm2 ) compared to CON ( type I : -164±290µm2 , p=0.04 ; and type II : -130±336µm2 , p=0.04 ) . This was accompanied by reduced insulin resistance [ ST : median ( interquartile range ) -0.7(3.6 ) vs CON : 0.8(3.8 ) , p=0.05 ] ; FFA ( ST : -84±30µmol/L vs CON : 149±48µmol/L , p=0.02 ) ; and CRP [ ST : -1.3(2.9)mg/L vs CON : 0.4(2.3)mg/L , p=0.05 ] . Serum adiponectin increased with ST [ 1.0(1.8)µg/mL ] compared to CON [ -1.2(2.2)µg/mL , p<0.001 ] . Strength training improved muscle quality and whole-body insulin sensitivity . Decreased inflammation and increased adiponectin levels were related with improved metabolic control . Further studies are needed to underst and the mechanisms associated with these findings . However , these data show that strength training is an exercise modality to consider as an adjunct of st and ard of care in high risk population s with type 2 diabetes The prevention of injury associated with falls in older people is a public health target in many countries around the world . Although there is good evidence that interventions such as multifactorial fall prevention and individually prescribed exercise are effective in reducing falls , the effect on serious injury rates is unclear . Historically , trials have not been adequately powered to detect injury endpoints , and variations in case definition across trials have hindered meta- analysis . It is possible that fall-prevention strategies have limited effect on falls that result in injuries or are ineffective in population s who are at a higher risk of injury . Further research is required to determine whether fall-prevention interventions can reduce serious injuries . Prevention of Falls Network Europe ( ProFaNE ) is a collaborative project to reduce the burden of fall injury in older people through excellence in research and promotion of best practice ( www.profane.eu.org ) . The European Commission funds the network , which links clinicians , members of the public , and research ers worldwide . The aims are to identify major gaps in knowledge in fall injury prevention and to facilitate the collaboration necessary for large-scale clinical research activity , including clinical trials , comparative research , and prospect i ve meta- analysis . Work is being undertaken in a 4-year program . As a first step , the development of a common set of outcome definitions and measures for future trials or meta- analysis was considered OBJECTIVE To examine the effects of an 8-week home-based resistance exercise program on balance , power , and mobility in adults with multiple sclerosis . DESIGN Experimental group design . SETTING General community . PARTICIPANTS Twenty-nine women ( age , 50.3+/-8.5 y ) and 8 men ( age , 51.1+/-7.1 y ) were stratified by disability level and age and were r and omized into exercise ( n=19 ) and control ( n=17 ) groups . INTERVENTION The exercise group had lower-extremity resistance training 3 times a week . The control group maintained current level of physical activity . Main outcome measures Primary outcome measures included balance , as measured by anteroposterior sway , mediolateral sway , and s Output:	CONCLUSION Exercise interventions can improve certain falls-related outcomes among older adults with DM . Among older adults , where DM burden is increasing , exercise interventions may provide promising approaches to assist the improvement of falls-related outcomes
MS2744	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The aim of this in vitro study was to evaluate the fracture load and marginal accuracy of crowns made from a shrinkage-free ZrSiO4 ceramic cemented with glass-ionomer or composite cement after chewing simulation . Thirty-two human m and ibular molars were r and omly divided into two groups . All teeth were prepared for and restored with shrinkage-free ZrSiO4 ceramic crowns ( Everest HPC , KaVo ) . The crowns of group A ( N = 16 ) were luted to the teeth using KetacCem and group B ( N = 16 ) were adhesively cemented using Panavia21EX . Measurements of the marginal accuracy before and after cementation were made using replicas and an image analysis system . All specimens were exposed to 1.2 million cycles of thermo-mechanical fatigue in a chewing simulator . Surviving specimens were subsequently loaded until fracture in a static testing device . Fracture loads ( N ) were recorded . All specimens survived chewing simulation . The mean fracture loads ( + /-s.d . ) were Group A , 1622 N ( + /-433 ) ; group B , 1957 N ( + /-806 ) . There was no significant difference between the two groups ( P > 0.05 ) . The marginal gap values before cementation were ( mean + /- s.d . ) : Group A , 32.7 microm ( + /-6.8 ) ; group B , 33.0 microm ( + /-6.7 ) . The mean marginal gap values after cementation were ( + /-s.d . ) : Group A , 44.6 microm ( + /-6.7 ) ; group B , 46.6 microm ( + /-7.7 ) . The marginal openings were significantly higher after cementation for both groups ( P < 0.05 ) . All test groups demonstrated fracture load and marginal accuracy values within the range of clinical acceptability PURPOSE This in vitro study investigated the marginal adaptation and fracture resistance of heat-pressed glass-ceramic and fiber-reinforced composite molar crowns luted with resin , resin-modified glass-ionomer , or zinc-oxide-eugenol-free cements . MATERIAL S AND METHODS A total of 24 heat-pressed all-ceramic and 24 glass fiber-reinforced composite crowns were constructed and cemented using the above-mentioned luting agents ( eight crowns per cement ) . The restorations were thermocycled and mechanically stressed , and fracture resistance was determined . Marginal adaptation was evaluated before and after stress application using semiquantitative analysis in a scanning electron microscope . RESULTS All-ceramic and fiber-reinforced composite crowns reached the highest fracture resistance after stress application in combination with the resin cement . When luted with resin-modified glass-ionomer or zinc-oxide-eugenol-free cements , the fracture resistance of all-ceramics decreased significantly , while the fiber-reinforced composite crowns maintained their fracture resistance level ; the lowest values were found for zinc-oxide-eugenol-free cements . The marginal adaptation remained unchanged after stress for all-ceramics and fiber-reinforced composite restorations if they were luted with resin cements . Luting with resin-modified glass-ionomers significantly deteriorated the marginal adaptation after stress application , with the exception of the crown-cement interface of all-ceramics . CONCLUSION The highest fracture resistance and marginal adaptation were found for all-ceramic and glass fiber-reinforced composite molar crowns if they were luted with resin cement BACKGROUND The authors analyzed the in vitro and in vivo performance of lithium disilicate glass-ceramic ( LDGC ) restorations and yttria-stabilized tetragonal zirconia polycrystalline ( Y-TZP ) ( that is , zirconium oxide ) restorations with regard to reliability , clinical performance and abrasion resistance . METHODS In the in vitro study , four authors subjected sample s of LDGC , Y-TZP and metal-ceramic crowns to step-stress fatigue testing . Four investigators assessed the in vivo clinical performance of LDGC and zirconium oxide-based restorations at four and seven years , respectively . In addition , one author conducted a r and omized , controlled clinical trial to analyze the volumetric loss of enamel and ceramic antagonist surfaces . RESULTS The LDGC crowns exhibited the highest fatigue load-to-failure values in the in vitro analysis . The results of the in vivo assessment showed that the clinical performance of the LDGC restorations at four years was comparable to that of the zirconium oxide-based crowns at seven years . The results of the in vivo , r and omized , controlled clinical trial showed that LDGC crowns were not only resistant to wear , but also were wear friendly to enamel antagonist surfaces . CONCLUSIONS The LDGC crowns in the in vitro and in vivo studies exhibited high durability , and they were wear friendly to opposing natural dentition . CLINICAL IMPLICATION S LDGC and zirconium oxide-based crowns are a clinical ly acceptable means of treating teeth that require full-coverage restorations . In addition , LDGC material s exhibit excellent clinical performance , as well as demonstrate acceptable abrasion compatibility with the opposing natural dentition STATEMENT OF PROBLEM The influence of different types of adhesive resin cements on the long-term prognosis of aluminum oxide ceramic posterior crowns is unclear . PURPOSE The purpose of this study was to evaluate the fracture resistance of aluminum oxide ceramic on maxillary posterior crowns cemented with different resin luting agents before and after cyclic thermomechanical loading . Material and methods Forty-eight maxillary first molars were prepared and restored with st and ardized aluminum oxide ceramic ( In-Ceram Alumina ) crowns . The test specimens were r and omly divided into 3 groups ( n=16 ) . The crowns were luted with an acrylic resin cement ( Super-Bond C&B , control , Group SB ) and 2 composite luting agents ( Panavia F , Group PV ; and Rely X Unicem , Group RX ) . Half of the specimens were exposed to thermomechanical fatigue in a masticatory simulator . All specimens were tested for fracture strength ( N ) using quasistatic loading . The Wilcoxon rank sum test was used to compare the fracture strength ( alpha=.05 ) . RESULTS All specimens survived the exposure to the simulator . The following median fracture strength values were obtained without/with thermomechanical fatigue loading : Group SB , 2726 N/2673 N ; Group PV , 2520 N/2083 N ; and Group RX , 2036 N/2369 N. The fracture strength in Group PV after thermomechanical fatigue loading was significantly lower compared to the fracture strength in Group PV without artificial aging ( P = .016 ) , as well as significantly lower compared to Group SB with artificial aging ( P = .003 ) . CONCLUSION Within the limitations of this study , all tested cements are capable of successfully luting aluminum oxide ceramic crowns . The fracture strength of Group PV after artificial aging was comparatively low The aim of the present study was to investigate the fracture resistance of zirconia crowns and to compare the results with crowns made of a material with known clinical performance ( alumina ) in away that reflects clinical aspects . Sixty crowns were made , 30 identical crowns of alumina and 30 of zirconia . Each group of 30 was r and omly divided into three groups of 10 crowns that were to undergo different treatments : ( i ) water storage only , ( ii ) pre-loading ( 10 000 cycles , 30 - 300 N , 1 Hz ) , ( iii ) thermocycling ( 5 - 55 degrees , 5000 cycles ) + pre-loading ( 10 000 cycles , 30 - 300 N , 1 Hz ) . Subsequently , all 60 crowns were subjected to load until fracture occurred . There were two types of fracture : total fracture and partial fracture . Fracture strengths ( N ) were : group 1 , alumina 905/zirconia 975 ( P = 0.38 ) ; group 2 , alumina 904/zirconia 1108 ( P < 0.007 ) and group 3 , alumina 917/zirconia 910 ( P > 0.05 ) . Total fractures were more frequent in the alumina group ( P < 0.01 ) . Within the limitations of this in vitro study , it can be concluded that there is no difference in fracture strength between crowns made with zirconia cores compared with those made of alumina if they are subjected to load without any cyclic pre-load or thermocycling . There is , however , a significant difference ( P = 0.01 ) in the fracture mode , suggesting that the zirconia core is stronger than the alumina core . Crowns made with zirconia cores have significantly higher fracture strengths after pre-loading PURPOSE Existing composite restorations on teeth are often remade prior to the cementation of fixed dental prostheses . The aim of this study was to evaluate the effect of static and cyclic loading on ceramic laminate veneers adhered to aged resin composite restorations . MATERIAL S AND METHODS Eighty sound maxillary incisors were collected and r and omly divided into four groups : group 1 : control group , no restorations ; group 2 : two Class III restorations ; group 3 : two Class IV restorations ; group 4 : complete composite substrate . St and ard composite restorations were made using a microhybrid resin composite ( Anterior Shine ) . Restored teeth were subjected to thermocycling ( 6000 cycles ) . Window preparations were made on the labial surface of the teeth for ceramic laminate fabrication ( Empress II ) . Teeth were conditioned using an etch- and -rinse system . Existing composite restorations representing the aged composites were silica coated ( CoJet ) and silanized ( ESPE-Sil ) . Ceramic laminates were cemented using a bis-GMA-based cement ( Variolink Veneer ) . The specimens were r and omly divided into two groups and were subjected to either static ( groups 1a , 2a , 3a , 4a ) or cyclic loading ( groups 1b , 2b , 3b , 4b ) . Failure type and location after loading were classified . Data were analyzed using one-way ANOVA and Tukey 's test . RESULTS Significantly higher fracture strength was obtained in group 4 ( 330 ± 81 N ) compared to the controls in group 1 ( 179 ± 120 N ) ( one-way ANOVA , p < 0.05 ) . Group 1b survived a lower mean number of cyclic loads ( 672,820 cycles ) than teeth of groups 2b to 4b ( 846x103 to 873x103 cycles ) . Failure type evaluation after the fracture test showed predominantly adhesive failures between dentin and cement , but after cyclic loading , more cohesive fractures in the ceramic were seen . CONCLUSION Ceramic laminate veneers bonded to conditioned aged composite restorations provided favorable results . Surface conditioning of existing restorations may eliminate the necessity of removing aged composite restorations Output:	An inclination for decreased static fracture strength could be observed after cyclic loading of all-ceramic single crowns and FDPs , but this was material specific .
MS2745	*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 Positron emission tomography ( PET ) imaging using [18F]fluorodeoxyglucose ( 18F-FDG ) is recognized to have a major role in oncological imaging . Over recent years there has been a steady increase in the use of gamma camera PET ( GCPET ) systems as these are less expensive than dedicated PET scanners and facilitate the full range of nuclear medicine imaging . However , there is ongoing debate about their application and usefulness in the management of oncological patients . Objectives To assess the feasibility of GCPET in a nuclear medicine department in a district general hospital remote from a cyclotron , compared with other imaging modalities in demonstrating disease in patients with large or locally advanced breast cancer . Methods 18F-FDG was transported by road from a production unit 100 miles from the imaging department . Twenty-five patients ( mean age 68 years ) with primary breast tumours measuring ≥20 mm on clinical examination were studied . All patients underwent triple assessment prior to PET imaging with an ADAC Solus camera with molecular coincidence detection capability . Histopathology was obtained in 20 cases following surgery . Results GCPET detected 24/25 primary breast tumours ( sensitivity 96 % ) . This compared with 22/25 ( 88 % ) for ultrasound and 15/25 ( 60 % ) for mammography . The lesion missed by PET was a grade 1 tumour , 8 mm in size . Conclusion In this pilot study GCPET has been shown to be feasible in a district general hospital , enabling a limited on-site PET imaging service to be provided . In the cases studied it was more sensitive than mammography or ultrasonography . GCPET may provide additional information that could be important in planning the management of some patients with breast cancer Background The role of positron emission tomography ( PET ) scanning in determining the extent of disease in patients with breast cancer has not been defined . We investigated the utility of 18F-2-fluoro-2-deoxy-D-glucose (FDG)-PET scanning compared with conventional imaging with computed tomographic scanning and bone scanning in determining the extent of disease in patients with high-risk , operable breast cancer . Methods This was a prospect i ve study of patients who presented to Memorial Sloan-Kettering Cancer Center for operative treatment of breast cancer . Eighty eligible patients were enrolled and underwent computed tomographic chest , abdomen , pelvis , and bone scans , followed by FDG-PET . Changes in treatment based on scan findings were recorded by the operating surgeons . Imaging findings were verified by biopsy or long-term follow-up . Results Eight ( 10 % ) of 80 patients were found to have metastatic disease that was seen on both conventional imaging and PET . Four additional patients ( 5 % ) had additional foci of disease on PET that affected treatment decisions . No patient had findings on conventional imaging alone . Conventional imaging studies result ed in a higher number of findings that generated additional tests and biopsies that ultimately had negative results ( 17 % vs. 5 % for PET ) . There was a statistically significant difference in specificity for PET compared with conventional imaging ( P = .01 ) . Conclusions Conventional imaging and PET were equally sensitive in detecting metastatic disease in patients with high-risk , operable breast cancer , but PET generated fewer false-positive results . FDG-PET scanning should be further studied in this setting and considered in the preoperative evaluation of selected patients with breast cancer We sought to prospect ively assess the diagnostic performance of a high-resolution positron emission tomography ( PET ) scanner using mild breast compression ( positron emission mammography [ PEM ] ) . Data were collected on concomitant medical conditions to assess potential confounding factors . At four centers , 94 consecutive women with known breast cancer or suspicious breast lesions received 18F-fluorodeoxyglucose ( FDG ) intravenously , followed by PEM scans . Readers were provided clinical histories and x-ray mammograms ( when available ) . After excluding inevaluable cases and two cases of lymphoma , PEM readings were correlated with histopathology for 92 lesions in 77 women : 77 index lesions ( 42 malignant ) , 3 ipsilateral lesions ( 3 malignant ) , and 12 contralateral lesions ( 3 malignant ) . Of 48 cancers , 16 ( 33 % ) were clinical ly evident ; 11 ( 23 % ) were ductal carcinoma in situ ( DCIS ) , and 37 ( 77 % ) were invasive ( 30 ductal , 4 lobular , and 3 mixed ; median size 21 mm ) . PEM depicted 10 of 11 ( 91 % ) DCIS and 33 of 37 ( 89 % ) invasive cancers . PEM was positive in 1 of 2 T1a tumors , 4 of 6 T1b tumors , 7 of 7 T1c tumors , and 4 of 4 cases where tumor size was not available ( e.g. , no surgical follow-up ) . PEM sensitivity for detecting cancer was 90 % , specificity 86 % , positive predictive value ( PPV ) 88 % , negative predictive value ( NPV ) 88 % , accuracy 88 % , and area under the receiver-operating characteristic curve ( Az ) 0.918 . In three patients , cancer foci were identified only on PEM , significantly changing patient management . Excluding eight diabetic subjects and eight subjects whose lesions were characterized as clearly benign with conventional imaging , PEM sensitivity was 91 % , specificity 93 % , PPV 95 % , NPV 88 % , accuracy 92 % , and Az 0.949 when interpreted with mammographic and clinical findings . FDG PEM has high diagnostic accuracy for breast lesions , including DCIS The present study compared the diagnostic accuracy of fluorine-18 2-deoxy-2-fluoro-D-glucose positron emission tomography ( FDG-PET ) with conventional staging techniques . The differentiation between malignant and benign lesions and the detection of multifocal disease , axillary and internal lymph node involvement , and distant metastases were evaluated . One hundred and seventeen female patients were prospect ively examined using FDG-PET and conventional staging methods such as chest X-ray , ultrasonography of the breast and liver , mammography and bone scintigraphy . All patients were examined on a modern full-ring PET scanner . Histopathological analysis of resected specimens was employed as the reference method . The readers of FDG-PET were blinded to the results of the other imaging methods and to the site of the breast tumour . The sensitivity and specificity of FDG-PET in detecting malignant breast lesions were 93 % and 75 % respectively . FDG-PET was twofold more sensitive ( sensitivity 63 % , specificity 95 % ) in detecting multifocal lesions than the combination of mammography and ultrasonography ( sensitivity 32 % , specificity 93 % ) . Sensitivity and specificity of FDG-PET in detecting axillary lymph node metastases were 79 % and 92 % ( 41 % and 96 % for clinical evaluation ) . FDG-PET correctly indicated distant metastases in seven patients . False-positive or false-negative findings were not encountered with FDG-PET . Chest X-ray was false-negative in three of five patients with lung metastases . Bone scintigraphy was false-positive in four patients . Three patients were upstaged since FDG-PET detected distant metastases missed with the st and ard staging procedure . It is concluded that , compared with the imaging methods currently employed for initial staging , FDG-PET is as accurate in interpreting the primary tumour and more accurate in screening for lymph node metastases and distant metastases . Due to a false-negative rate of 20 % in detecting axillary lymph node metastases , FDG-PET can not replace histological evaluation of axillary status BACKGROUND The aim of this work is to assess the diagnostic value of positron emission tomography ( PET ) with 18F-fluorodeoxyglucose ( FDG ) , in the early detection of tumour recurrence in already treated breast cancer patients in apparent complete remission and with a progressive elevation of tumour markers CEA and /or CA 15.3 without any other clinical or instrumental signs of relapses . METHODS The author studied 45 women ( mean age 58+/-12 , range 35 - 80 years ) with histological diagnosis of breast cancer who underwent a tumour marker-guided whole body FDG-PET . All patients were in remission , without any other clinical or instrumental signs of relapses , except for the progressive elevation of CA 15.3 and /or CEA , tested during the follow-up . FDG-PET results were controlled by pathology when histological sampling was possible , by other conventional imaging modalities ( US , X-rays , CT , MRI ) and /or by clinical follow-up up to 12 months at least . RESULTS FDG-PET findings were evaluated in 38 patients : 27 result ed positive . Among these 27 PET positive patients 24 were true positive and 3 false positive . Tumour marker guided FDG-PET was also able to discover 3 unknown neoplasms not visualized by other modalities . PET revealed 54 sites of intense focal FDG uptake . The anatomical distribution of these sites was 19 skeleton , 18 lymph node basins , 5 liver , 5 pelvic region , 1 lung , 1 pericardium , 1 pleura , 1 contralateral breast , 2 peritoneum and 1 thyroid bed . Forty-eight of these 54 sites of FDG accumulation were confirmed to be metastases . FDG-PET result ed negative in 11 patients and only in 2 of them the other diagnostic modalities were able to discover metastatic lesions ; we had 9 true negative and 2 false positive RESULTS . On the basis of our investigation the performances of tumour marker guided FDG-PET per patient are as follows : sensitivity 92 % ( 24/26 ) , specificity 75 % ( 9/12 ) , positive predictive value 89 % ( 24/27 ) , negative predictive value 82 % ( 9/11 ) , accuracy 87 % ( 33/38 ) . CONCLUSIONS This study demonstrated the clinical utility of tumour marker-guided PET in the follow-up of breast cancer patients . This diagnostic approach allowed to modify the clinical management in those patients in whom a tumor relapse or unexpected primary neoplasm was discovered RATIONALE AND OBJECTIVES The authors performed this study to determine the feasibility of using quantitative 2-[fluorine-18]fluoro-2-deoxy-D-glucose ( FDG ) positron emission tomography ( PET ) to monitor the response of breast cancer bone metastases to therapy . MATERIAL S AND METHODS Twenty-four women with stage IV bone-dominant breast carcinoma were included in this study . Whole-body FDG PET imaging was performed at serial time points during the course of therapy . FDG PET scans were interpreted quantitatively by using the maximum st and ard uptake value ( SUV ) of the most conspicuous bone lesion at baseline FDG PET . PET results were compared to the overall assessment of response ( response , stable disease , progressive disease ) with a combination of conventional imaging , change in tumor marker values , and subjective symptom changes by experienced medical oncologists blinded to the findings at FDG PET . Changes in FDG SUV were also correlated quantitatively to the changes in a particular tumor marker ( CA 27.29 ) . RESULTS The changes in FDG SUV with therapy showed correlation with the overall clinical assessment of response ( P < .01 ) . The percentage change in FDG uptake with therapy showed strong correlation with the percentage change in tumor marker value ( P < .01 ) . CONCLUSION Preliminary results indicate that serial whole-body FDG PET can help quantitatively assess the response of breast cancer bone metastases to therapy . Prospect i ve trials are needed to further investigate its accuracy BACKGROUND Although axillary lymph node status is an important prognostic factor and axillary dissection is regarded as the gold st and ard for staging , it requires radical surgery which is accompanied by considerable postoperative problems such as lymphedema . This study was carried out to evaluate the diagnostic accuracy of preoperative positron emission tomography ( PET ) and intraoperative frozen biopsy of sentinel lymphadenectomy ( SLND ) in detecting axillary lymph node metastasis . METHODS We studied 18 patients who had preoperative PET and SLND for breast cancer in the Department of Surgery at Samsung Medical Center . They all had preoperative PET with a radiolabeled glucose analogue ( [18F]FDG ) to visualize primary tumors and metastatic nodes . Isosulphan blue dye was used for intraoperative SLND . Frozen and permanent biopsies were then compared after full axillary dissection . RESULTS In 18 cases , six had positive metastatic nodes in the permanent biopsy of full axillary dissection but were negative in three cases by preoperative PET . There was one false negative result by frozen biopsy of SLND which was later shown to be positive by permanent biopsy . The sensitivity and specificity of SLND and PET for detecting axillary node metastasis were 83 , 100 % and 50 , 100 % , respectively . CONCLUSION Although both methods are good for axillary nodal status , the intraoperative frozen biopsy result of SLND was Output:	FDG-PET does not appear to be sufficiently accurate to be used in isolation for ruling out the presence of a primary tumour . In lymph gl and staging , FDG-PET does not appear to be accurate enough to detect occult axillary metastases or micrometastases ( sensitivity 20 and 50 % , respectively ) ; sentinel node biopsy is required for confirmation . In the detection of bone metastases , FDG-PET should be complemented with other tests such as bone gammagraphy or SPECT . The assessment of response to chemotherapy , there seems to be no uniform criterion for establishing a st and ardized uptake value ( SUV ) for FDG that would allow responders and non-responders to be distinguished . Conclusions FDG-PET is insufficiently sensitive to rule out small primary tumours . Due to the high number of false positives returned , it can not replace axillary dissection in axillary lymph gl and staging . A complete biochemical response identified by FDG-PET should not be relied upon to mean an absence of disease since the technique can not detect residual microscopic elements
MS2746	*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: Adolescent anxiety is debilitating , the most frequently diagnosed adolescent mental health problem , and leads to substantial long-term problems . A r and omized controlled trial ( n = 138 ) was conducted to test the effectiveness of a biofeedback video game ( Dojo ) for adolescents with elevated levels of anxiety . Adolescents ( 11–15 years old ) were r and omly assigned to play Dojo or a control game ( Rayman 2 : The Great Escape ) . Initial screening for anxiety was done on 1,347 adolescents in five high schools ; only adolescents who scored above the “ at-risk ” cut-off on the Spence Children Anxiety Survey were eligible . Adolescents ’ anxiety levels were assessed at pre-test , post-test , and at three month follow-up to examine the extent to which playing Dojo decreased adolescents ’ anxiety . The present study revealed equal improvements in anxiety symptoms in both conditions at follow-up and no differences between Dojo and the closely matched control game condition . Latent growth curve models did reveal a steeper decrease of personalized anxiety symptoms ( not of total anxiety symptoms ) in the Dojo condition compared to the control condition . Moderation analyses did not show any differences in outcomes between boys and girls nor did age differentiate outcomes . The present results are of importance for prevention science , as this was the first full-scale r and omized controlled trial testing indicated prevention effects of a video game aim ed at reducing anxiety . Future research should carefully consider the choice of control condition and outcome measurements , address the potentially high impact of participants ’ expectations , and take critical design issues into consideration , such as individual- versus group-based intervention and contamination issues Background Depression often emerges for the first time during adolescence . There is accumulating evidence that universal depression prevention programs may have the capacity to reduce the impact of depression when delivered in the school environment . Objective This trial investigated the effectiveness of SPARX-R , a gamified online cognitive behavior therapy intervention for the prevention of depression relative to an attention-matched control intervention delivered to students prior to facing a significant stressor — final secondary school exams . It was hypothesized that delivering a prevention intervention in advance of a stressor would reduce depressive symptoms relative to the control group . Methods A cluster r and omized controlled trial was conducted in 10 government schools in Sydney , Australia . Participants were 540 final year secondary students ( mean 16.7 [ SD 0.51 ] years ) , and clusters at the school level were r and omly allocated to SPARX-R or the control intervention . Interventions were delivered weekly in 7 modules , each taking approximately 20 to 30 minutes to complete . The primary outcome was symptoms of depression as measured by the Major Depression Inventory . Intention-to-treat analyses were performed . Results Compared to controls , participants in the SPARX-R condition ( n=242 ) showed significantly reduced depression symptoms relative to the control ( n=298 ) at post-intervention ( Cohen d=0.29 ) and 6 months post-baseline ( d=0.21 ) but not at 18 months post-baseline ( d=0.33 ) . Conclusions This is the first trial to demonstrate a preventive effect on depressive symptoms prior to a significant and universal stressor in adolescents . It demonstrates that an online intervention delivered in advance of a stressful experience can reduce the impact of such an event on the potential development or exacerbation of depression . Trial Registration Australian New Zeal and Clinical Trials Registry ACTRN12614000316606 ; https://www.anzctr.org.au/Trial/ Registration /Trial Review .aspx?id=365986 ( Archived by WebCite at http://www.webcitation.org/ 6u7ou1aI9 BACKGROUND Children with anxious or depressive symptoms are at risk of developing internalizing disorders and their attendant morbidity . To prevent these outcomes , school-based cognitive-behavioral therapy ( CBT ) has been developed , but few studies include active control conditions . We evaluated a preventive CBT program targeting internalizing symptoms relative to an activity contrast condition post-intervention and at 1-year follow-up . METHODS One thous and one hundred and thirty-nine children from Grade s 3 - 6 from a diverse sample of schools , were screened with the Multidimensional Anxiety Scale for Children and Children 's Depression Inventory . Those with t>60 on either measure were offered participation in a r and omized 12-week trial , school-based group CBT versus a structured after-school activity group of equal duration . We explored several therapeutic elements as potential predictors of change . RESULTS One hundred and forty-eight children participated ( 84 boys , 64 girls ; 78 CBT , 70 contrast ; 57 % Caucasian ) and 145 completed the program . Self-reported anxious and depressive symptoms decreased significantly over time ( η(2)=.15 and .133 , respectively ) , with no group by time interaction . There was a trend toward fewer children meeting diagnostic criteria for an anxiety disorder on the Anxiety Disorders Interview Schedule at 1-year post-CBT than post-contrast ( 6/76 versus 12/69 ) . Positive reinforcement of child behavior was associated with change in anxiety symptoms ; checking homework was understood with change in depressive symptoms . CONCLUSIONS Findings suggest that children with internalizing symptoms may benefit from both school-based CBT and structured activity programs . Replication , longer follow-up , and further studies of therapeutic elements in child CBT are indicated . IS RCT N Registry identifier : IS RCT N88858028 , url : Although few prevention studies have been design ed to investigate the course of prevention effects over time , it seems that the effects on depressive symptoms increase from post-intervention to 6-month follow-up but then decrease with longer lags to follow-up . Furthermore , previous prevention studies have found differential intervention effects for boys and girls without testing possible explanations for this effect . The present r and omized control group study with 301 8th- grade students examined the effects of a depression prevention program from baseline until 12-month follow-up . As expected , while positive intervention effects were found on girls ' depressive symptoms , no such effects were found on boys ' depressive symptoms . Further , the positive intervention effects on girls ' depressive symptoms increased to the 6-month follow-up and remained stable through the 12-month follow-up , while depression symptoms in control-group girls increased from 6-month to 12-month follow-up . Further exploratory analyses revealed that neither baseline conduct problems nor cognitive or social knowledge of the prevention program at 12-month follow-up alone explained the sex effect . However , some limited evidence was found indicating that total knowledge ( cognitive and social ) might partially explain the effect but there was significant variability remaining to be explained BACKGROUND Anxiety in children is common , impairs everyday functioning , and increases the risk of severe mental health disorders in adulthood . We investigated the effect of a classroom-based cognitive behaviour therapy prevention programme ( FRIENDS ) on anxiety symptoms in children . METHODS Preventing Anxiety in Children though Education in Schools ( PACES ) is a three-group parallel cluster r and omised controlled trial . Interventions were given between September , 2011 , and July , 2012 , with schools as the unit of allocation and individual participants as the unit of analysis . We enrolled state-funded junior schools in southwest Engl and . We sent information to all eligible schools ( state-funded junior schools in southwest Engl and ) inviting them to enrol in the study . School year groups were assigned by computer-generated r and omisation ( 1:1:1 ) to receive either school-led FRIENDS ( led by teacher or school staff member ) , health-led FRIENDS ( led by two trained health facilitators ) , or usual school provision . Children were not masked to treatment allocation . The allocated programme was given to all students ( aged 9 - 10 years ) in the school year ( ie , universal delivery ) as part of the school curriculum as nine , 60 min weekly sessions . Outcomes were collected by self-completed question naire administered by research ers masked to allocation . Primary outcome was symptoms of anxiety and low mood at 12 months assessed by the Revised Child Anxiety and Depression Scale ( RCADS 30 ) . Analyses were intention to treat and accounted for the clustered nature of the design . The study is registered , number IS RCT N23563048 . FINDINGS 45 schools were enrolled : 14 ( n=497 children ) were r and omly assigned to school-led FRIENDS , 14 ( n=509 ) to health-led FRIENDS , and 12 ( n=442 ) to usual school provision . 1257 ( 92 % ) children completed 12 month assessment s ( 449 in health-led FRIENDS , 436 in school-led FRIENDS , and 372 in usual school provision ) . We recorded a difference at 12 months in adjusted mean child-reported RCADS scores for health-led versus school-led FRIENDS ( 19·49 [ SD 14·81 ] vs 22·86 [ 15·24 ] ; adjusted difference -3·91 , 95 % CI -6·48 to -1·35 ; p=0·0004 ) and health-led FRIENDS versus usual school provision ( 19·49 [ 14·81 ] vs 22·48 [ 15·74 ] ; -2·66 , -5·22 to -0·09 ; p=0·043 ) . We noted no differences in parent or teacher ratings . Training teachers to deliver mental health programmes was not as effective as delivery by health professionals . INTERPRETATION Universally delivered anxiety prevention programmes can be effective when used in schools . However , programme effectiveness varies depending on who delivers them . FUNDING National Institute for Health Research Public Health Research Programme PURPOSE Although cognitive-behavioral interventions have been successful in treating depression , no studies were found that focused solely on reducing negative thinking via group intervention as a means of preventing depression in at-risk groups . The purpose of this r and omized controlled trial was to test the effectiveness of a cognitive-behavioral group intervention in reducing depressive symptoms , decreasing negative thinking , and enhancing self-esteem in young women at risk for depression . DESIGN A r and omized controlled trial with 92 college women ages 18 to 24 who were at risk for depression was conducted . METHOD Participants were r and omly assigned to either the control or experimental group . The experimental group participated in a 6-week cognitive-behavioral group intervention . Data on self-esteem , depressive symptoms , and negative thinking were collected via self-report question naires from control and experimental groups at baseline , 1 month after the intervention , and at 6-month follow-up . Data were analyzed using mixed-model methodology and the Cochran-Mantel-Haenszel chi-square test . FINDINGS Compared to those in the control group , women who received the intervention had a greater decrease in depressive symptoms and negative thinking and a greater increase in self-esteem , and these beneficial effects were maintained over 6-months . CONCLUSIONS The findings document the effectiveness of this cognitive-behavioral group intervention and indicate empirical support for the beneficial effects of reducing negative thinking by the use of affirmations and thought-stopping techniques on women 's mental health Youth in underserved , urban communities are at risk for a range of negative outcomes related to stress , including social-emotional difficulties , behavior problems , and poor academic performance . Mindfulness-based approaches may improve adjustment among chronically stressed and disadvantaged youth by enhancing self-regulatory capacities . This paper reports findings from a pilot r and omized controlled trial assessing the feasibility , acceptability , and preliminary outcomes of a school-based mindfulness and yoga intervention . Four urban public schools were r and omized to an intervention or wait-list control condition ( n = 97 fourth and fifth grade rs , 60.8 % female ) . It was hypothesized that the 12-week intervention would reduce involuntary stress responses and improve mental health outcomes and social adjustment . Stress responses , depressive symptoms , and peer relations were assessed at baseline and post-intervention . Findings suggest the intervention was attractive to students , teachers , and school administrators and that it had a positive impact on problematic responses to stress including rumination , intrusive thoughts , and emotional arousal A large proportion of children experience sub clinical levels of anxiety and cognitive-behavioral therapy ( CBT ) aim ed at preventing anxiety disorders is moderately effective . However , most at-risk children do not seek help or drop out of programs prematurely because of stigma , lack of motivation , and accessibility barriers . Applied games have received increased attention as viable alternatives and have shown promising results , but direct comparisons between applied games and the gold-st and ard CBT are lacking . Our aim was to investigate whether the applied game MindLight is as effective as CBT ( i.e. , Coping Cat ) within an indicated prevention context . We conducted a r and omized controlled non-inferiority trial with a sample of 174 children ( 7- to 12-year olds ) with elevated levels of anxiety , comparing MindLight to CBT . Anxiety was assessed with self- and parent-reports at pre- and post-program , and at 3- and 6-month follow-ups . Intention-to-treat and completers-only confidence interval approach and latent growth curve modeling showed an overall significant quadratic decrease in child- and parent-reported anxiety symptoms over time and , as predicted , the magnitude of improvement was the same for MindLight and CBT . The within-group effect sizes were small to medium at post-test ( − 0.32 to − 0.63 ) , and medium to large ( − 0.60 to − 1.07 ) at Output:	There was a lack of evidence to support any one type of intervention being effective to prevent depression in universal or targeted primary or secondary setting s. Comparison-adjusted funnel plots suggest the presence of small- study effects for the universal secondary anxiety analysis . INTERPRETATION Considering unclear risk of bias and probable small study effects for anxiety , we conclude there is little evidence that educational setting -based interventions focused solely on the prevention of depression or anxiety are effective .
MS2747	*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 recent increased utilization of industrial back belts as personal protective equipment in the workplace has generated considerable controversy among occupational health and safety professionals in the United States . The purpose of this article is to review the literature regarding proposed mechanisms of action of these devices and studies related to outcome of belt utilization in the prevention of low back pain and disability in the workplace . At the present time , neither the suspected mechanisms of action nor the efficacy of these devices in the primary , secondary , and tertiary prevention of work-related low back pain has been adequately demonstrated in clinical trials . As a result , generally accepted guidelines regarding the safe use of belts in the occupational setting have not been established . Based on this review it is recommended that further well-controlled , prospect i ve , r and omized clinical trials are necessary to evaluate the effectiveness of these devices as personal protective equipment . During the interim , the decision to prescribe belts to employees in the workplace should be at the discretion of an adequately trained occupational health care provider . These devices should not be provided as an alternative to appropriate administrative and /or engineering controls Radiographic instability seemingly enjoys the status of a well-defined clinical syndrome . The concept is widely used , and specific treatments , usually spinal fusion , are routinely performed based on the diagnosis . The minimum st and ards necessary to establish radiographic instability as a legitimate clinical syndrome have not been established , however . The primary purpose of this study was to determine if treatment involving bracing , exercise , and education controlling either flexion or extension postures , would result in a distinctive pattern of favorable or unfavorable results , depending on the type of radiographic instability ( retrodisplacement or spondylolisthesis ) . Fifty-six patients meeting strict study inclusion and radiographic evaluation criteria were assigned signed to a bracing treatment ( flexion , extension , placebo-control ) according to a r and omization scheme , design ed to ensure equal representation of translation categories ( retro , normal , spondy ) across treatment groups , and assessed at admission and 1-month follow-up . The sample was relatively evenly divided between men ( 46 % ) and women ( 54 % ) , and by age . Translation classification was related to both gender and age , with men more likely classified as retro and women more likely spondy and patients in their 20s having lower incidence of spondy and higher incidence of normal translation . Translation classification was not related to selected indices of low-back pain history . Brace treatments were not shown to reduce patient range of motion or lessen trunk strength . A significant treatment by time interaction for the modified pain interference ( VAS ) scale indicated improvement for patients in extension compared with patients in flexion and control-placebo treatments . In conjunction with no significant three-way interaction between treatment , translation classification , and time , it was hypothesized that radiographic instability might more appropriately be considered a corroborative sign of advanced discogenic problems . Improvement in extension treatment , regardless of the type of radiographic abnormality , suggests that the treating clinician might consider extension treatment for chronic low-back pain patients . Causes and implication s for the failure of this study to provide support for considering radiographic instability as a clinical syndrome are considered and future directions for this area of research suggested This study was design ed to determine the effect of multimodal intervention and the prevention of back injury , and to evaluate the adverse side effects of using a lumbosacral corset in the workplace . Subjects were 90 male warehouse workers r and omly selected from over 800 employees at a grocery distribution center . Subjects were assigned to three groups : true controls , no back school , no brace orthoses ; back school only ; and back school plus wearing a custom molded lumbosacral orthosis . Comparisons of pre-testing and 6-month follow-up posttesting for abdominal strength , cognitive data , work injury incidence and productivity and use of health care services were evaluated . Controls and training-only group showed no changes in strength productivity or lost time . Orthoses and training-group showed no changes in strength productivity or accident rate ; however , they showed substantially less lost time . This study supports the concept of using education and prophylactic bracing to prevent back injury and reduce time loss . It appears that the use of intermittent prophylactic bracing has no adverse affects on abdominal muscle strength and may contribute to decreased lost time from work injuries Study Design A r and omized prospect i ve trial of manipulation , massage , corset and transcutaneous muscle stimulation ( TMS ) was conducted in patients with subacute low back pain . Objectives The authors determined the relative efficacy of chiropractic treatment to massage , corset , and TMS . Summary of Background Data Although all of these treatments are used for subacute low back pain treatment , there have been few comparative trials using objective outcome criteria . Patients were enrolled for a period of 3 weeks . They were evaluated once a week by question naires , visual analog scale , range of motion , maximum voluntary extension effort , straight leg raising and Biering-Sorensen fatigue test . The dropout rate was highest in the muscle stimulation and corset groups and lowest in the manipulation group . Rates of full compliance did not differ significantly across treatments . A measure of patient confidence was greatest in the manipulation group . Results After 3 weeks , the manipulation group scored the greatest improvements in flexion and pain while the massage group had the best extension effort and fatigue time , and the muscle stimulation group the best extension . Conclusion None of the changes in physical outcome measures ( range of motion , fatigue , strength or pain ) were significantly different between any of the groups A prospect i ve epidemiologic study was conducted in two units ( 140 beds and 57 nursing assistants ) of a nursing home to demonstrate the efficacy of an ergonomic intervention strategy to reduce back stress to nursing personnel . The total programme involved the following : determining patient h and ling tasks perceived to be most stressful by the nursing assistants ( NAs ) ; performing an ergonomic evaluation of these tasks ; and conducting a laboratory study to select patient transferring devices perceived to produce less physical stress than existing manual patient-h and ling methods . The intervention phase included training NAs in the use of these devices , modifying toilets and shower rooms , and applying techniques to patient care . Immediately after completing the intervention programme , a post-intervention analysis ( which lasted eight months in unit 1 and four months in unit 2 ) was performed . A biomechanical evaluation of the physical dem and s required to perform stressful patient-h and ling tasks showed that the mean compressive force on the L5/S1 disc , the mean h and force required to make a transfer , and the strength requirements ( expressed as percentage female population capable ) were 1964 N , 122 N , and 83 % after intervention as compared to 4751 N , 312 N , and 41 % before intervention . Subjectively , the mean rating of perceived exertion was less than ' very light ' after intervention as compared to between ' somewhat hard ' and ' hard ' before intervention . Overall , the mean acceptability rates for the walking belt and the mechanical hoist were 81 % and 87 % for patient transfers . The incidence rate for back injuries prior to the intervention , 83 per 200,000 work-hours , decreased to 47 per 200,000 work-hours after the intervention . There were no injuries result ing in lost or restricted work days during the last four months of the post-intervention . It is concluded that an appropriate ergonomic intervention programme offers great promise in reducing physical stress and risk of low-back pain to nursing personnel . However , large-scale studies in different nursing homes are needed to confirm the above findings Output:	There was moderate evidence that for primary prevention lumbar supports are not more effective than other types of treatment or no intervention . No evidence was found on the effectiveness of lumbar supports for secondary prevention . The systematic review of therapeutic trials showed that there is limited evidence that lumbar supports are more effective than no treatment , while it is still unclear if lumbar supports are more effective than other interventions for treatment of low back pain .
MS2748	*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 eluci date the time course and magnitude of hemodynamic and fibrinolytic changes associated with sequential gradient intermittent pneumatic compression ( SGIPC ) . DESIGN Two-phase , intervention and response investigation in normal volunteers . MATERIAL S AND METHODS Subjects were assigned to control ( phase I ) or compression ( phase II ) groups . Serial blood sample s were obtained via femoral venous catheters for tissue plasminogen activator ( tPA ) , plasminogen activator inhibitor ( PAI-1 ) , tPA-PAI-1 complex ( tPA-PAI ) , and euglobulin lysis time ( ELT ) from all subjects and for fibrin degradation products ( FbDP ) and fibrinogen degradation products ( FgDP ) from phase II subjects . Duplex venous scanning was carried out on phase II subjects before and during SGIPC . RESULTS Catheter placement caused elevations in PAI-1 and tPA-PAI , which stabilized within 4 hours of catheter insertion . In phase II , SGIPC induced significant increases in FbDP , FgDP , and tPA-PAI and decreases in ELT and PAI-1 , all of which quickly reverted to baseline on termination of compression . Femoral venous blood flow increased by more than 100 % with SGIPC . CONCLUSIONS Sequential gradient intermittent pneumatic compression induces prompt , but short-lived , alterations in both fibrinolytic and hemodynamic function . Noncontinuous SGIPC may result in suboptimal thromboembolic prophylaxis Introduction This prospect i ve study was design ed to confirm risk factors and to assess the incidence of deep vein thrombosis after total hip and surface replacement arthroplasty in Korean patients not receiving anticoagulation prophylaxis and to determine efficacy of plasma D-dimer levels as a screening test . Material s and methods From May 2003 to August 2004 , 221 consecutive patients undergoing unilateral total hip arthroplasty and hip resurfacing were evaluated . All patients underwent ultrasonography preoperatively and venography and /or ultrasonography on postoperative day 7 . Plasma D-dimer levels were estimated by latex immuno-assay preoperatively and on days 3 and 7 postoperatively . Results Of the 221 patients in our cohort , 23 developed deep vein thrombosis ( 10.4 % ) . Age ( r = 0.245 , P < 0.001 ) and gender ( r = 0.155 , P = 0.021 ) significantly correlated with deep vein thrombosis . Rise in incidence paralleled increase in age ( X2 = 32.860 , P < 0.001 ) . D-dimer levels on postoperative days 3 ( γ = 0.364 , P < 0.001 ) and 7 ( γ = 0.470 , P < 0.001 ) were significantly correlated to the development of DVT . Conclusion While incidence of deep vein thrombosis in Korean population after THA was lower than that in the West ; it increased with age , and in female gender . Significant correlation was found between D-dimer levels and the development of deep vein thrombosis D-dimers may be elevated after surgery . However , the kinetics of postoperative D-dimers remains unknown hampering the use of D-dimer testing in surgical patients with suspected venous thromboembolism . D-dimer levels were prospect ively measured in 154 patients after general surgery at predefined time points ( kinetics were determined in an initial cohort of 108 patients ; for validation , these findings were applied to a second cohort of 46 patients ) . Clinical factors influencing the peak of D-dimers were analyzed using multivariate regression . Surgical operations were stratified based on severity ( type I : not entering abdominal cavity ; type II : intraabdominal ; type III : retroperitoneal/liver surgery ) . D-dimer levels increased postoperatively reaching a peak on day 7 . After type I surgery , peak D-dimer levels did not exceed normal range ( 300 ng/ml , 100–500 ) . After type II procedures , peak D-dimer level was 1500 ng/ml ( 200–7800 ) and returned to normal values after 25 days ( ±14 ) . Peak level was 4000 ng/ml ( 500–14 400 ) after type III surgery normalizing within 38 days ( ±11 ) . Clearance of D-dimer was exponential after having reached the peak with 6.0 % per day ( 95 % confidence interval 4.8–7.1 % ) . By this clearance , D-dimer values could be adequately predicted in the validation cohort after day 7 ( r2 = 0.63 ) . Peak D-dimer levels were independently influenced by the type of surgery ( P < 0.001 ) , the operation time ( P < 0.001 ) and by preoperatively elevated D-dimer levels ( P < 0.001 ) . Based on this data , duration of postoperative D-dimer elevation after abdominal surgery is predictable . This study indicates for the first time when D-dimers may be used again in the diagnostic algorithm for venous thromboembolism exclusion after surgery in patients with low or moderate clinical probability The WizAir-DVT is a miniature , lightweight ( 690 g ) , battery-operated and mobile intermittent pneumatic compression device ( ICD ) , which enables continuous intraoperative use and immediate patient mobilization postoperatively . We compared its efficacy with a commonly used ICD , the Kendall SCD . Peak femoral vein flow velocity was measured in 20 apparently healthy volunteers at rest and with each device : we found no significant differences between them . A second prospect i ve , r and omized , clinical trial was used to compare the efficiency of the device in preventing deep venous thrombosis ( DVT ) after joint replacement in 50 patients ( n=25/group ) . None developed DVT . Doppler ultrasonography revealed no significant differences . The WizAir-DVT antithrombotic compression device is as safe and effective as the Kendall SCD Background : Intermittent pneumatic foot compression ( IPC ) is a useful technique for prophylaxis of peri‐operative venous thromboembolism . The aim of this study was to determine the effect of IPC on blood coagulation/fibrinolysis and platelet function using a blood viscometer ( SonoclotTM ) and a platelet aggregation monitor ( WBA analyzerTM ) , respectively . Using the same blood sample s , serum levels of tissue‐type plasminogen activator ( t‐PA ) , thrombomodulin ( TM ) and activated protein C ( APC ) were also measured The purpose of this study was to evaluate the efficacy of two intermittent pneumatic compression devices as prophylaxis against intravascular coagulation and leg swelling following total hip arthroplasty . We studied 121 patients by assessing thrombogenesis using the D-dimer level before and after total hip arthroplasty . In addition , the patients ’ postoperative swelling was evaluated by measuring the thigh and lower leg circumference . Altogether , 58 patients were assigned to the calf-thigh pneumatic compression group , and the other 63 were assigned to the plantar compression group ; the two pneumatic compression devices were compared to evaluate which was more effective for reducing thrombogenesis . At 7 days postoperatively , the mean D-dimer levels of the calf-thigh compression group and the plantar compression group were 8.86 and 9.26 µg/ml , respectively . There was no significant difference ( P = 0.697 ) between the two groups . However , the increased ratio of the circumference of the thigh , which was compared after arthroplasty , averaged 1.22 % in the calf-thigh compression group and 3.19 % in the plantar compression group , which was significantly different ( P ≪ 0.01 ) . Calf-thigh pneumatic compression was found to be more effective than plantar compression for reducing thigh swelling during the early postoperative stage A crossover study was performed to evaluate the effect of several pneumatic compression devices and active dorsoplantar flexion in 10 patients who underwent total hip arthroplasty . Using the Acuson 128XP/10 duplex ultrasound unit with a 5-MHz linear array probe , peak venous velocity and venous volume were assessed above and below the greater saphenous vein and common femoral vein junction . A computer generated r and omization table was used to determine the order of the test conditions . The pneumatic compression devices evaluated included two foot pumps , one foot and calf pump , one calf pump , and three calf and thigh pumps . Statistical analyses included analysis of variance and analysis of variance with covariance between devices and patients . The covariates tested were the baseline measurements and the order in which the devices were tested . Differences between devices relate in part to the frequency and rate of inflation and the location and type of compression . Pulsatile calf and foot and calf pneumatic compression with a rapid inflation time produced the greatest increase in peak venous velocity , whereas compression of the calf and thigh showed the greatest increase in venous volume . Because patient and nursing compliance is essential to the success of mechanical prophylaxis for thromboembolic disease , the more simple , yet efficacious , devices that are easier to apply and less cumbersome appear to have a greater likelihood of success . In the active and alert patient , active dorsoplantar flexion should be encouraged BACKGROUND AND OBJECTIVES Intermittent pneumatic compression ( IPC ) is an effective form of deep vein thrombosis prophylaxis for general surgery patients . The antithrombotic effect of IPC is thought to be the result of increased venous velocity and stimulation of endogenous fibrinolysis . However , the mechanism of enhanced fibrinolytic activity and the relative effects on normal and postthrombotic veins have not been defined . The purpose s of this study are 1 ) to quantify changes in fibrinolytic activity with IPC ; 2 ) to study the mechanism of fibrinolytic enhancement with IPC ; and 3 ) to evaluate whether postthrombotic patients have the same capacity for fibrinolytic enhancement with IPC as do normal subjects . METHODS Twelve volunteers ( 6 normal and 6 postthrombotic ) had 5 IPC devices applied for 120 minutes in r and om fashion , 1 per week x 5 weeks . The devices included single-chamber , sequential , foot , calf , and long-leg compression . Subjects had an indwelling antecubital venous cannula placed for blood drawn at baseline , 60 , 120 , and 180 minutes after IPC devices were applied . Global fibrinolytic activity ( euglobulin fraction , fibrin plate assay ) , tissue plasminogen activator ( tPA ) antigen ( Ag ) and activity ( Act ) , plasminogen activator inhibitor-1 ( PAI-1 ) Ag and Act , alpha-2-antiplasmin-plasmin complexes , and von Willebr and factor ( vWF ) antigen were assayed . RESULTS A striking elevation in fibrinolytic activity was noted at 180 minutes with all devices in normal subjects and postthrombotic patients ( p = 0.01 - 0.0001 ) ; however , baseline and stimulated fibrinolytic activity was attenuated in postthrombotic patients ( < 0.03 ) . The tPA-Act increased only in normal subjects ( 3.8 + /- 1.9 % ) ( p = 0.057 ) , despite a decrease in plasma tPA-Ag , which was observed in both normal subjects ( -12.4 + /- 3.8 % ) ( p = 0.009 ) and patients ( -17.2 + /- 3.1 % ) ( p = 0.001 ) . PAI-1-Ag decreased in both normal subjects ( -13.4 + /- 3.8 % ) ( p = 0.007 ) and patients ( -12.0 + /- 3.1 % ) ( p = 0.013 ) with a marked reduction in PAI-1-Act in both normal subjects ( p = 0.003 ) and patients ( p = 0.004 ) . There were no changes in vWF , and alpha-2-antiplasmin-plasmin complexes increased only in postthrombotic patients ( p = 0.021 ) . CONCLUSIONS Stimulation of endogenous fibrinolytic activity occurs after IPC , both in normal subjects and postthrombotic patients ; however , baseline and overall fibrinolytic response in postthrombotic patients is reduced . The mechanism of increased fibrinolytic activity is likely because of a reduction in PAI-1 , with a result ing increase of tPA activity After total hip ( THR ) or knee replacement ( TKR ) , there is still an appreciable risk of developing deep-vein thrombosis despite prophylaxis with low-molecular-weight heparin ( LMWH ) . In a prospect i ve , r and omised study we examined the efficacy of LMWH in combination with intermittent pneumatic compression in patients undergoing primary unilateral THR or TKR . We administered 40 mg of enoxaparin daily to 131 patients combined with either the use of intermittent pneumatic compression or the wearing of graduated compression stockings . Compression ultrasonography showed no evidence of thrombosis after LMWH and intermittent pneumatic compression . In the group with LMWH and compression stockings the prevalence of thrombosis was 28.6 % ( 40 % after TKR , 14 % after THR ) . This difference was significant ( p < 0.0001 Output:	The authors found no cases of symptomatic DVT or PE in either the calf-thigh compression group or the plantar compression group during the first three weeks after the THR . The calf-thigh pneumatic compression was more effective than plantar compression for reducing thigh swelling during the early postoperative stage . There is a lack of evidence from r and omized controlled trials to make an informed choice of IPC device for preventing venous thromboembolism ( VTE ) following total hip replacement .
MS2749	*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: Interferon therapy may exacerbate health-related quality of life ( HRQL ) deficits associated with hepatitis C virus ( HCV ) early in the course of therapy . Treatment with polyethylene glycol-modified interferon ( peginterferon ) alfa-2a ( 40 kd ) provides improved sustained response over interferon alfa-2a , but its effect on HRQL is unknown . The objective of this study was to ( 1 ) evaluate the effect of sustained virologic response on HRQL in patients with HCV and ( 2 ) determine whether impairment of HRQL during treatment contributes to early treatment discontinuation . Data consisted of a pooled secondary analysis of patients ( n = 1,441 ) across 3 international , multicenter , open-label , r and omized studies that compared peginterferon alfa-2a ( 40 kd ) with interferon alfa-2a . ANCOVA was used to examine the effect of sustained virologic response on HRQL . Repeated- measures mixed-models ANCOVA was used to compare Fatigue Severity Scale ( FSS ) and SF-36 scores during treatment by treatment group . Logistic regression analysis was used to examine the association between changes at baseline in on-treatment HRQL and early treatment discontinuation . Sustained virologic response was associated with marked improvements from baseline to end of follow-up in all subjects , including patients with cirrhosis . During treatment , patients receiving peginterferon alfa-2a ( 40 kd ) had statistically significantly better scores on both the SF-36 and FSS . Baseline to 24-week changes in fatigue and SF-36 mental and physical summary scores significantly predicted treatment discontinuation . In conclusion , sustained virologic response is associated with improvements in quality of life in patients with or without advanced liver disease . This parameter may be an important consideration in maximizing treatment adherence The new Cobas Core Anti-HCV EIA was evaluated in two centers for its ability to detect antibodies directed to hepatitis C virus in human serum . This assay , which can be run fully automated on a r and om access analyzer , was compared with three other commercially available screening tests : the Ortho HCV 3.0 ELISA , the Murex anti-HCV , and the Abbott HCV EIA second generation . Positive or discrepant results were further investigated using the Wellcozyme HCV Western Blot or the Abbott Matrix HCV assays . The results obtained from analyzing 5045 serum sample s showed a high correlation between the Cobas Core Anti-HCV EIA and the other screening assays , ranging from 98.9 % to 99.9 % . Diagnostic specificities and sensitivities ranged from 99.7 % to 100 % and from 98.8 % to 100 % , respectively . In this study , the Cobas Core Anti-HCV EIA proved to be a very convenient test , able to perform at the highest levels of sensitivity and specificity The risk of complications from percutaneous liver biopsy is low , but discomfort is common and complications require hospitalization in approximately 4 % of patients . The optimal method of performing these biopsies is unknown . The goal of our study was to determine whether the use of ultrasonography in the biopsy room immediately prior to or during the procedure would lessen the risk of complications and to compare the safety and efficacy in obtaining tissue by use of a Trucut needle versus an automatic biopsy needle . Between 1992 and 1994 , 836 patients were entered into a r and omized study ( 489 in Rochester , MN ; 347 in Barcelona , Spain ) . Patients were r and omized immediately prior to liver biopsy into four groups : Trucut needle , or automatic biopsy needle , and with or without ultrasonography . Fisher 's Exact Test and a logistic regression model were also used to assess the effect of needle and ultrasonography on the odds for complications . The four biopsy groups were well-matched at entry with respect to age , sex , underlying liver disease , hemoglobin , prothrombin time , and platelet count . The use of ultrasound was associated with a decreased rate of hospitalization for pain , hypotension , or bleeding ( 2 vs. 9 , P < .05 ) . No difference in safety was found between the two types of needles . The number of passes needed to obtain specimens was similar for all four groups . The average length of the specimen was slightly greater with ultrasonographic-guided biopsies ( 1.7 mm vs. 1.6 mm , P < .05 ) and with biopsies obtained using the automatic biopsy needle when compared with the Trucut needle ( 1.7 mm vs. 1.5 mm , P < .05 ) , but this did not seem to be clinical ly important . The addition of ultrasonography reduces complications in patients undergoing percutaneous liver biopsy . The type of needle appears to offer little difference in safety or yield of diagnostic tissue . The use of ultrasonography for guidance of percutaneous liver biopsy will lead to a lower rate of complications . The value of this benefit must be weighed against the added cost of ultrasonographic guidance BACKGROUND A sustained virological response ( SVR ) rate of 41 % has been achieved with interferon alfa-2b plus ribavirin therapy of chronic hepatitis C. In this r and omised trial , peginterferon alfa-2b plus ribavirin was compared with interferon alfa-2b plus ribavirin . METHODS 1530 patients with chronic hepatitis C were assigned interferon alfa-2b ( 3 MU subcutaneously three times per week ) plus ribavirin 1000 - 1200 mg/day orally , peginterferon alfa-2b 1.5 microg/kg each week plus 800 mg/day ribavirin , or peginterferon alfa-2b 1.5 microg/kg per week for 4 weeks then 0.5 microg/kg per week plus ribavirin 1000 - 1200 mg/day for 48 weeks . The primary endpoint was the SVR rate ( undetectable hepatitis C virus [ HCV ] RNA in serum at 24-week follow-up ) . Analyses were based on patients who received at least one dose of study medication . FINDINGS The SVR rate was significantly higher ( p=0.01 for both comparisons ) in the higher-dose peginterferon group ( 274/511 [ 54 % ] ) than in the lower-dose peginterferon ( 244/514 [ 47 % ] ) or interferon ( 235/505 [ 47 % ] ) groups . Among patients with HCV genotype 1 infection , the corresponding SVR rates were 42 % ( 145/348 ) , 34 % ( 118/349 ) , and 33 % ( 114/343 ) . The rate for patients with genotype 2 and 3 infections was about 80 % for all treatment groups . Secondary analyses identified bodyweight as an important predictor of SVR , prompting comparison of the interferon regimens after adjusting ribavirin for bodyweight ( mg/kg ) . Side-effect profiles were similar between the treatment groups . INTERPRETATION In patients with chronic hepatitis C , the most effective therapy is the combination of peginterferon alfa-2b 1.5 microg/kg per week plus ribavirin . The benefit is mostly achieved in patients with HCV genotype 1 infections BACKGROUND Chronic hepatitis C virus ( HCV ) infection in patients with cirrhosis is difficult to treat . In patients with chronic hepatitis C but without cirrhosis , once-weekly administration of interferon modified by the attachment of a 40-kd branched-chain polyethylene glycol moiety ( peginterferon alfa-2a ) is more efficacious than a regimen of unmodified interferon . We examined the efficacy and safety of peginterferon alfa-2a in patients with HCV-related cirrhosis or bridging fibrosis . METHODS We r and omly assigned 271 patients with cirrhosis or bridging fibrosis to receive subcutaneous treatment with 3 million units of interferon alfa-2a three times weekly ( 88 patients ) , 90 microg of peginterferon alfa-2a once weekly ( 96 ) , or 180 microg of peginterferon alfa-2a once weekly ( 87 ) . Treatment lasted 48 weeks and was followed by a 24-week follow-up period . We assessed efficacy by measuring HCV RNA and alanine aminotransferase and by evaluating liver-biopsy specimens . A histologic response was defined as a decrease of at least 2 points on the 22-point Histological Activity Index . RESULTS In an intention-to-treat analysis , HCV RNA was undetectable at week 72 in 8 percent , 15 percent , and 30 percent of the patients treated with interferon alfa-2a and with 90 microg and 180 microg of peginterferon alfa-2a , respectively ( P=0.001 for the comparison between 180 microg of peginterferon alfa-2a and interferon alfa-2a ) . At week 72 , alanine aminotransferase concentrations had normalized in 15 percent , 20 percent , and 34 percent of patients , respectively ( P=0.004 for the comparison between 180 microg of peginterferon alfa-2a and interferon alfa-2a ) . In the subgroup of 184 patients with paired liver-biopsy specimens , the rates of histologic response at week 72 were 31 percent , 44 percent , and 54 percent , respectively ( P=0.02 for the comparison between 180 microg of peginterferon alfa-2a and interferon alfa-2a ) . All three treatments were similarly tolerated . CONCLUSIONS In patients with chronic hepatitis C and cirrhosis or bridging fibrosis , 180 microg of peginterferon alfa-2a administered once weekly is significantly more effective than 3 million units of st and ard interferon alfa-2a administered three times weekly Seroprevalence data from the Third National Health and Nutrition Examination Survey ( 1984 to 1999 ) suggest that 3 million persons in the United States are infected with the hepatitis C virus ( HCV ) ( 1 ) . Treatment fails to clear the virus in 80 % to 85 % of acutely infected persons . Not all persons who remain infected eventually develop progressive liver disease ( 2 ) , but in those who do , clinical evidence of liver damage may not appear until decades later ( 3 ) . It is widely believed that progression of liver disease in persons with chronic HCV infection is enhanced by concomitant heavy alcoholism ( 4 - 12 ) . We sought to quantify the association of transfusion-associated HCV infection and history of alcohol abuse with development of cirrhosis among patients followed from the time of acute HCV infection . Methods The source of this investigation , described in detail elsewhere ( 13 ) , is a long-term follow-up study of acute non-A , non-B hepatitis in patients included in earlier prospect i ve studies of transfusion-related HCV infection . All patients provided informed consent , and the study was approved by the relevant institutional review boards . Briefly , non-A , non-B hepatitis was identified by otherwise unexplained elevations in serum alanine aminotransferase ( ALT ) levels developing 2 to 24 weeks after transfusion , in the absence of serologic evidence of hepatitis A or B ( 13 ) . The ALT level had to be elevated on two consecutive measurements , and at least one of the values had to exceed twice the upper limit of normal . Stored sera from case- patients and controls from three of the prospect i ve studies the second Veterans Administration Cooperative study ( 14 ) , the Transfusion-Transmitted Viruses study ( 15 ) , and the National Institutes of Health Blood Bank Study (16)were tested for anti-HCV by enzyme immunoassay ( HCV EIA 2.0 , Abbott Laboratories , North Chicago , Illinois ) . Transfusion-associated HCV infection was diagnosed if anti-HCV appeared and persisted , was temporally related to elevated ALT levels , and was confirmed by using the supplementary recombinant immunoblot assay ( RIBA version 3.0 , Ortho Diagnostics , Raritan , New Jersey ) . Because repository sample s were not optimally stored for minimizing nucleic acid loss , HCV RNA testing was not performed . Controls consisted of transfused patients from the original three prospect i ve studies who had not developed hepatitis ( 13 ) . Controls were matched to case- patients by initial treatment center , sex , ethnicity , use of hepatitis immune globulin , presence or absence of a history of alcoholism , age , number of units of blood transfused , and date of transfusion . We excluded patients with anti-HCVpositive sample s that pre date d the index transfusion and those with anti-HCV reactivity but no confirmatory test . Anti-HCVpositive/RIBA-negative and anti-HCVnegative patients were classified as having transfusion-associated non-A , non-B , non-C hepatitis . Controls with anti-HCV in repository sample s were excluded . We used a multifaceted approach to gather information on each patient 's history of liver disease from participation in the prospect i ve studies through initiation of the follow-up study ( 13 ) . Vital status was ascertained through search es of death registries , and copies of death certificates were obtained . Patients or their design ated proxies ( if the patient was deceased or incompet Output:	Data from Large Observational Studies on Independent Risk Factors for Positive Status on Tests for AntiHepatitis C Virus Antibody All 4 large population -based studies also found an independent association between HCV infection and high-risk sexual behaviors ( variably defined , but usually considered sex with multiple partners or sex with an HCV-infected person ) . In most setting s with a low prevalence of intravenous drug use , high-risk sexual behaviors are the strongest risk factor for HCV infection ( 56 - 60 ) .
MS2750	*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 Treatment with a gonadotropin-releasing hormone agonist decreases bone mineral density and increases the risk of fracture in men with prostate cancer . We conducted a controlled study of the prevention of osteoporosis in men undergoing treatment with a gonadotropin-releasing hormone agonist . METHODS In a 48-week , open-label study , we r and omly assigned 47 men with advanced or recurrent prostate cancer and no bone metastases to receive either leuprolide alone or leuprolide and pamidronate ( 60 mg intravenously every 12 weeks ) . Bone mineral density of the lumbar spine and the proximal femur was measured by dual-energy x-ray absorptiometry . Trabecular bone mineral density of the lumbar spine was measured by quantitative computed tomography . Forty-one men completed the study . RESULTS In men treated with leuprolide alone , the mean ( + /-SE ) bone mineral density decreased by 3.3+/-0.7 percent in the lumbar spine , 2.1+/-0.6 percent in the trochanter , and 1.8+/-0.4 percent in the total hip , and the mean trabecular bone mineral density of the lumbar spine decreased by 8.5+/-1.8 percent ( P<0.001 for each comparison with the base-line value ) . In contrast , the mean bone mineral density did not change significantly at any skeletal site in men treated with both leuprolide and pamidronate . There were significant differences between the two groups in the mean changes in bone mineral density at 48 weeks in the lumbar spine ( P<0.001 ) , trochanter ( P = 0.003 ) , total hip ( P=0.005 ) , and trabecular bone of the lumbar spine ( P=0.02 ) . CONCLUSIONS Pamidronate prevents bone loss in the hip and lumbar spine in men receiving treatment for prostate cancer with a gonadotropin-releasing hormone agonist Bone mineral density ( BMD ) and bone mineral content ( BMC ) were measured in the femoral neck area , trochanteric area and Wards triangle , and in the distal radius of the left forearm before and after 1 year of endocrine treatment in 27 patients with prostatic cancer . Eleven of the patients were treated with orchidectomy and 16 with combined oral and intramuscular estrogens . The patients were free from metastases during the entire observation period . In the orchidectomized patients , BMD and BMC of the distal radius decreased significantly following treatment , whereas no changes were observed in the estrogen-treated patients . These preliminary results demonstrate that estrogens may protect bone in male subjects also and may merit further investigations on larger groups of patients PURPOSE And rogen deprivation therapy is associated with fracture risk in men with prostate cancer . We assessed the effects of toremifene , a selective estrogen receptor modulator , on fracture incidence in men receiving and rogen deprivation therapy during a 2-year period . MATERIAL S AND METHODS In this double-blind , placebo controlled phase III study 646 men receiving and rogen deprivation therapy for prostate cancer were assigned to toremifene ( 80 mg by mouth daily ) and 638 were assigned to placebo . Subjects were followed for 2 years . The primary study end point was new vertebral fractures . Secondary end points included fragility fractures , bone mineral density and lipid changes . RESULTS The 2-year incidence of new vertebral fractures was 4.9 % in the placebo group vs 2.5 % in the toremifene group , a significant relative risk reduction of 50 % ( 95 % CI -1.5 to 75.0 , p = 0.05 ) . Toremifene significantly increased bone mineral density at the lumbar spine , hip and femoral neck vs placebo ( p < 0.0001 for all comparisons ) . There was a concomitant decrease in markers of bone turnover ( p < 0.05 for all comparisons ) . Toremifene also significantly improved lipid profiles . Venous thromboembolic events occurred more frequently with toremifene than placebo with 7 subjects ( 1.1 % ) in the placebo group experiencing a venous thromboembolic event vs 17 ( 2.6 % ) in the toremifene group . Other adverse events were similar between the groups . CONCLUSIONS Toremifene significantly decreased the incidence of new vertebral fractures in men receiving and rogen deprivation therapy for prostate cancer . It also significantly improved bone mineral density , bone turnover markers and serum lipid profiles PURPOSE Gonadotropin-releasing hormone ( GnRH ) agonists decrease bone mineral density ( BMD ) and increase fracture risk in men with prostate cancer . Annual zoledronic acid increases BMD in postmenopausal women , but its efficacy in hypogonadal men is not known . PATIENTS AND METHODS In a 12-month study , 40 men with nonmetastatic prostate cancer who were receiving a GnRH agonist and had T scores more than -2.5 were r and omly assigned to zoledronic acid ( 4 mg intravenously on day 1 only ) or placebo . BMD of the posteroanterior lumbar spine and proximal femur were measured by dual-energy x-ray absorptiometry . RESULTS Mean ( + /- SE ) BMD of the posteroanterior lumbar spine decreased by 3.1 % + /- 1.0 % in men assigned to placebo and increased by 4.0 % + /- 1.0 % in men assigned to zoledronic acid ( P < .001 ) . BMD of the total hip decreased by 1.9 % + /- 0.7 % in men assigned to placebo and increased by 0.7 % + /- 0.5 % in men assigned to zoledronic acid ( P = .004 ) . Similar between-group differences were observed for the femoral neck and trochanter . Serum N-telopeptide , a marker of osteoclast activity , decreased significantly after zoledronic acid treatment . CONCLUSION In men receiving a GnRH agonist , a single treatment with zoledronic acid significantly increased BMD and durably suppressed serum N-telopeptide levels for 12 months . Annual zoledronic acid may be a convenient and effective strategy to prevent bone loss in hypogonadal men To report a r and omized , placebo‐controlled study of treatment with zoledronic acid every 3 months in patients with hormone‐sensitive prostate cancer , both with and without bone metastases , to assess the effect on bone mineral density ( BMD ) and markers of bone turnover PURPOSE And rogen deprivation therapy for prostate cancer is associated with osteoporosis and increased fracture risk . Previous studies of zoledronic acid demonstrated bone loss prevention in patients initiating and rogen deprivation therapy . There are limited data on patients on prolonged and rogen deprivation therapy or in Veterans Affairs patients with multiple risk factors for osteoporosis . METHODS We r and omized 93 patients with M0 prostate cancer in this placebo controlled trial in the Veterans Affairs health care system . Preplanned strata included 50 patients on and rogen deprivation therapy for less than 1 year ( stratum 1 ) and 43 on and rogen deprivation therapy for greater than 1 year ( stratum 2 ) . In each stratum patients were r and omized to 4 mg zoledronic acid intravenously every 3 months for 4 treatments or intravenous placebo . The primary end point was the percent change in bone mineral density at the lumbar spine at 12 months . RESULTS Age , race , body mass index and osteoporosis risk factors were similar for the 2 treatments . Most patients were former smokers , had moderate alcohol intake , were not on calcium/vitamin D supplements and were relatively sedentary at baseline . In stratum 1 spine bone mineral density increased 5.95 % in the zoledronic acid arm and decreased 3.23 % in the placebo arm ( p = 0.0044 ) . In stratum 2 spine bone mineral density increased 6.08 % in the zoledronic acid arm and only increased 1.57 % in the placebo arm ( p = 0.0005 ) . Treatment was well tolerated with minimal impact on renal function . CONCLUSIONS Zoledronic acid improved bone mineral density in patients with M0 prostate cancer on and rogen deprivation therapy for 1 year or less , or greater than 1 year . This finding indicates that bisphosphonate therapy remains effective when initiated later in the course of and rogen deprivation therapy and is efficacious in Veterans Affairs patients with multiple risk factors for osteoporosis UNLABELLED Today , and rogen deprivation therapy is a cornerstone of treatment for advanced prostate cancer , although it presents important complications such as osteoporosis . Neridronate , a relatively new bisphosphonate , is able to prevent bone loss in patients with prostate cancer during and rogen ablation . INTRODUCTION And rogen-deprivation therapy ( ADT ) is a cornerstone of treatment for advanced prostate cancer . This therapy has iatrogenic complications , such as osteoporosis . The aim of our study was to evaluate the efficacy of neridronate , a relatively new bisphosphonate , to prevent bone loss during and rogen ablation . MATERIAL S AND METHODS Forty-eight osteoporotic patients with prostate cancer , treated with 3-month depot triptorelina , were enrolled and r and omly assigned to two different treatment groups : group A ( n = 24 ) was treated with a daily calcium and cholecalciferol supplement ( 500 mg of elemental calcium and 400 IU cholecalciferol ) , and group B ( n = 24 ) received in addition to the same daily calcium and cholecalciferol supplement , 25 mg of neridronate given intramuscularly every month . All patients also received bicalutamide for 4 weeks . Lumbar and femoral BMD was evaluated by DXA at baseline and after 1 year of therapy ; moreover , deoxypyridinoline ( DPD ) and bone alkaline phosphatase ( BALP ) were determined at the beginning , midway through , and at the end of the study . RESULTS After 6 and 12 months , whereas patients treated only with calcium and cholecalciferol ( group A ) showed a marked bone loss , with increased levels of DPD and BALP compared with baseline values , patients treated also with neridronate ( group B ) had substantially unchanged levels of these markers . After 1 year of treatment , lumbar and total hip BMD decreased significantly in patients treated only with calcium and cholecalciferol ( group A ) , whereas it did not change significantly at any skeletal site in patients treated also with neridronate ( group B ) . No relevant side effects were recorded during our study . CONCLUSIONS Neridronate is an effective treatment in preventing bone loss in the hip and lumbar spine in men receiving ADT for prostate cancer Objectives : Long-term results of radiotherapy in locally advanced prostate cancer are poor due to local and distant failures . Since prostate cancer is hormone dependent , tumor and rogen deprivation may enhance tumor eradication . Methods : Three r and omized phase III trials , RTOG and EORTC are reported : they assess and rogen suppression by using a luteinizing hormone-releasing hormone analogue ( LH-RHa ) with or without and rogen blockade before and during , or during and after external irradiation . Results : A gain in disease-free , local relapse-free and metastasis-free survival has been obtained ( p < 0.001 ) . Only the EORTC 22863 trial has reported a significant improvement in overall survival ( p = 0.001 ) with an LH-RHa started the first day of radiotherapy and administered every 4 weeks over 3 years . In the RTOG 85 - 10 trial , and LH-RHa , initiated in the last week of radiation therapy and continued until relapse , increased overall survival only in patients with poorly differentiated tumor with a Gleason score of 8–10 ( p = 0.03 ) . Conclusion : And rogen suppression prior to and during radiation improves disease-free survival ; adjuvant hormonal therapy with an LH-RHa during and after radiation improves overall survival OBJECTIVE And rogen-deprivation therapy ( ADT ) is the usual treatment for locally advanced or metastatic prostate cancer . Osteoporosis is a common complication of ADT . The aim of our study was to evaluate the efficacy of neridronate , a relatively new bisphosphonate to prevent bone loss during and rogen ablation . METHODS Sixty patients with prostate cancer and osteoporosis were enrolled and r and omly assigned to 2 different treatment regimes : group A ( 30 patients ) treated with maximum and rogenic blockage ( MAB ) , and group B ( 30 patients ) treated with bicalutamide 150 mg . Each group was divided in 2 subgroups A1-A2 and B1-B2 . All patients received calcium and cholecalciferol supplements ( 500 mg of elemental calcium and 400 IU cholecalciferol ) daily . The A2 and B2 subgroups were also treated with neridronate ( 25 mg intramuscular monthly ) . Lumbar and femoral bone mineral density ( BMD ) was evaluated by dualenergy X-ray absorptiometry ( DXA ) , both at baseline and after one year of treatment . Deoxypyridinoline ( DPD ) and bone-alkaline phosph Output:	However , there was no significant reduction in fractures . Currently , our meta- analysis suggested that oral and intravenous bisphosphonates caused a rapid increase in spine and hip or femoral BMD in non-metastatic prostate cancer patients receiving and rogen-deprivation therapy . Fever and gastrointestinal symptoms were common with the use of bisphosphonates . These short-term trials ( maximum of 12 months ) did not show fracture reduction .
MS2751	*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 objective of this study was to assess synergistic antioxidant properties of vitamin C and isoflavones . The design was a placebo-controlled crossover trial : 500 mg vitamin C , 5 mg/kg body weight isoflavones , 500 mg vitamin C plus 5 mg/kg body weight isoflavones , or placebo . Total lipid peroxides , plasma vitamin C , and blood pressure were measured . Eight of 10 healthy postmenopausal women completed the study . A multiple analysis of variance was performed and least-squares difference post-hoc test utilized to determine where differences occurred . Significance was defined as P < .05 . There was a significant reduction in total lipid peroxides between baseline and isoflavone treatments ( 3.22+/-0.72 vs 2.47+/-0.82 nmol/mL , P < .05 ) . Mean systolic blood pressure was higher during isoflavone intervention than placebo ( 117+/-14 vs 125+/-15 mm Hg , P= .042 ) . Supplementation with vitamin C and isoflavones did not produce a synergistic antioxidant effect . A slight but significant increase in systolic blood pressure occurred with isoflavone supplementation . A larger study should be conducted to fully explore the potential interactions between these antioxidants The objectives of the study were to clarify the relationship between blood pressure and mortality from stroke , heart disease , cardiovascular diseases and all causes of death among representative population of Japanese and to estimate category-specific excess mortality from stroke due to blood pressure ( BP ) level . The study design comprised a retrospective cohort study using the 1980 National Survey on Cardiovascular Diseases and identification of underlying causes of death using national vital statistics data . In 1994 , a 14-year follow-up cohort study was conducted among participants of the National Survey on Cardiovascular Diseases in 1980 , r and omly selected from the Japanese population . With a collaboration of 300 public health centres , which had conducted the original survey in 1980 , 91.4 % of the participants of the original survey could be followed up . Total observed person-years were 53 948 for men and 70 932 for women . During follow-up , 1327 deaths were observed . BP levels were significantly related to mortality from strokes , cardiovascular diseases and all causes of death for both sexes ( P<0.001 ) . Heart disease mortality was significantly related to BP levels among men ( P<0.05 ) while not among women . Estimated excess mortality was 130 % for men and 42 % for women and chiefly observed among moderate hypertensives ( 48 % for men and 16 % for women ) . In conclusion , high blood pressure was a risk factor for mortality from all causes as well as those from cardiovascular diseases , stroke and heart disease among Japanese . Since the major part of excess mortality was due to mild hypertension , a population strategy to reduce blood pressure should be encouraged BACKGROUND a small number of reports exist on the cognitive effects of soy isoflavones , the findings from which are mixed . Isoflavone efficacy is dependent upon conversion of glycosides contained in soy foods and supplements to the biologically active aglycons . Of particular interest is the production of the metabolite , equol , which is dependent upon intestinal microflora and an integrous digestive system , both being altered by age and age-associated conditions . Unfortunately , few studies enrolled adults over the age of 70 , and none included older men . OBJECTIVE we examined safety , feasibility and cognitive efficacy of soy isoflavone administration in older nondemented men and women ( age 62 - 89 years ) . DESIGN AND METHODS in this r and omised , placebo-controlled , double-blind pilot study , subjects ingested either 100 mg/day soy isoflavones ( glycoside weight ) or matching placebo tablets for 6 months . RESULTS active and placebo-treated subjects exhibited a comparable side-effect profile . Plasma levels of genistein and daidzein ( P < 0.001 ) , but not equol , increased with isoflavone administration . While similar at baseline , the two groups differed across 6 months of treatment on 8 of 11 cognitive tests administered . Isoflavone-treated subjects improved on tests of visual-spatial memory ( P < 0.01 ) and construction ( P = 0.01 ) , verbal fluency ( P < 0.01 ) and speeded dexterity ( P = 0.04 ) . Placebo-treated participants were faster than isoflavone-treated subjects on two tests of executive function ( P < 0.05 ) . CONCLUSIONS these data suggest that administration of 100 mg/day of isoflavones was well tolerated . Plasma genistein and daidzein levels , but not equol , increased with isoflavone administration . Finally , data support the potential cognitive effects of soy isoflavones in older adults BACKGROUND Soy foods contain several components ( isoflavones and amino acids ) that potentially affect bone . Few long-term , large clinical trials of soy as a means of improving bone mineral density ( BMD ) in late postmenopausal women have been conducted . OBJECTIVE Our goal was to evaluate the long-term effect of dietary soy protein and /or soy isoflavone consumption on skeletal health in late postmenopausal women . DESIGN We conducted a r and omized , double-blind , placebo-controlled clinical trial in 131 healthy ambulatory women aged > 60 y. Ninety-seven women completed the trial . After a 1-mo baseline period , subjects were r and omly assigned into 1 of 4 intervention groups : soy protein ( 18 g ) + isoflavone tablets ( 105 mg isoflavone aglycone equivalents ) , soy protein + placebo tablets , control protein + isoflavone tablets , and control protein + placebo tablets . RESULTS Consumption of protein powder and isoflavone pills did not differ between groups , and compliance with the study powder and pills was 80 - 90 % . No significant differences in BMD were observed between groups from baseline to 1 y after the intervention or in BMD change between equol and non-equol producers . However , there were significant negative correlations between total dietary protein ( per kg ) and markers of bone turnover ( P < 0.05 ) . CONCLUSIONS Because soy protein and isoflavones ( either alone or together ) did not affect BMD , they should not be considered as effective interventions for preserving skeletal health in older women . The negative correlation between dietary protein and bone turnover suggests that increasing protein intakes may suppress skeletal turnover . This trial was registered at Clinical Trials.gov as NCT00668447 OBJECTIVES It has been suggested that isoflavones protect the cardiovascular system , in part by improving lipid profile . The purpose of the present research was to examine the effect of a 12-week soy isoflavone supplementation on lipoprotein status and platelet thromboxane A2 receptor density . METHODS Twenty-nine healthy postmenopausal women were invited to take part in a r and omised study to receive either 100 mg/day isoflavone supplement ( n=15 ) or identical placebo capsules ( n=14 ) . Blood sample s obtained at baseline and after 12 weeks were analysed for isoflavones , total cholesterol , high density lipoprotein cholesterol , triglycerides , glucose , insulin , estradiol , testosterone , gonadotrophins , sex hormone-binding globulin ( SHBG ) and platelet thromboxane A2 receptor density . Blood pressure measurements , body mass index , subcutaneous fat at entrance and at the end of treatment were also registered . Changes in variables between groups were compared by ANOVA for repeated measures . RESULTS Blood pressure , body mass index , subcutaneous fat , insulin , serum lipoprotein , sex hormones and SHBG did not differ among groups . However , platelet thromboxane A2 receptor density declined significantly ( from 181.9+/-30.9 to 115.2+/-16.2 fmol/10(8 ) platelets ) in the experimental group , remaining mostly unchanged in the placebo group ( 176.3+/-27.3 to 170.4+/-28.2 fmol/10(8 ) platelets ) . The dissociation constant ( Kd ) values were unchanged . The change in platelet thromboxane A2 receptors correlated negatively with isoflavones serum concentration ( r=-0.59 , p<0.001 ) . CONCLUSIONS In this study we demonstrated that the beneficial effects of isoflavones in menopausal women could be more related to platelet function than to improving classical cardiovascular risk factors Background and Purpose We estimated the incidence of first-ever cerebral infa rct ion in regard to its subtypes and analyzed their risk factors separately in a community-based prospect i ve cohort study in Japan . Methods Stroke-free subjects ( n=1621 ) aged ≥40 years were followed up for 32 years from 1961 . During this period , 298 cerebral infa rct ions occurred and were divided into 167 lacunar , 62 atherothrombotic , 56 cardioembolic , and 13 undetermined subtypes of infa rct ion on the basis of clinical information including brain imaging and autopsy findings . Results The age-adjusted incidence of lacunar infa rct ion ( 3.8 per 1000 person-years for men and 2.0 for women ) was higher than that of atherothrombotic infa rct ion ( 1.2 , 0.7 ) and cardioembolic infa rct ion ( 1.3 , 0.5 ) in both sexes . Time-dependent Cox ’s proportional hazard analysis revealed systolic blood pressure as well as age to be independent risk factors for all subtypes of cerebral infa rct ion except for cardioembolic infa rct ion in men . Additionally , ST depression on ECG , glucose intolerance , and smoking in men and left ventricular hypertrophy on ECG and body mass index in women remained significant risk factors for lacunar infa rct ion . ST depression was also significantly related to events of atherothrombotic infa rct ion in women . The risk of atrial fibrillation for cardioembolic infa rct ion was outst and ingly high in both sexes , and left ventricular hypertrophy and lower total cholesterol were additional risk factors for cardioembolic infa rct ion in women . Conclusions In this Japanese population , lacunar infa rct ion was the most common subtype of cerebral infa rct ion and had a greater variety of risk factors , including not only hypertension but also ECG abnormalities , diabetes , obesity , and smoking , than did atherothrombotic infa rct ion or cardioembolic infa rct ion The phytoestrogen genistein improves endothelial dysfunction in ovariectomized rats through a nitric oxide-dependent mechanism . We investigated whether genistein alters the balance between the nitric oxide products and endothelin-1 and influences endothelium-dependent vasodilation in postmenopausal women . Sixty healthy postmenopausal women were enrolled in the study . A double-blind , placebo controlled , r and omized design was employed . After a 4-week stabilization on a st and ard fat-reduced diet , participants to the study were r and omly assigned to receive either genistein ( n=30 ; 54 mg/day ) or placebo ( n=30 ) . Flow-mediated , endothelium-dependent vasodilation of the brachial artery , plasma nitric oxide breakdown products and endothelin-1 levels were measured at baseline and after 6 months of genistein therapy . The mean baseline level of nitrites/nitrates was 22+/-10 micromol/l and increased to 41+/-10 micromol/ml after 6 months of treatment . The mean baseline plasma endothelin-1 level was 14+/-4 pg/ml and decreased to 7+/-1 pg/ml following 6 months of treatment with genistein . The mean baseline ratio of nitric oxide to endothelin also significantly increased at the end of treatment . Flow-mediated , endothelium-dependent vasodilation of the brachial artery was 3.9+/-0.8 mm at baseline and increased to 4.4+/-0.7 mm after 6 months of treatment . Placebo-treated women showed no changes in plasma nitrites/nitrates , endothelin-1 levels and flow-mediated vasodilation . Genistein therapy improves flow-mediated endothelium dependent vasodilation in healthy postmenopausal women . This improvement may be mediated by a direct effect of genistein on the vascular function and could be the result of an increased ratio of nitric oxide to endothelin OBJECTIVE To examine the change in menopausal symptoms and cardiovascular risk factors in response to 4 months of daily 100‐mg soy isoflavone in postmenopausal women . METHODS In this double‐blind , placebo‐controlled study , 80 women were r and omly assigned to isoflavone ( n = 40 ) and placebo ( n = 40 ) treatment . The menopausal Kupperman index was used to assess change in menopausal symptoms at baseline and after 4 months of treatment . Cardiovascular risk factors were assessed by evaluating plasma lipid levels , body mass index , blood pressure , and glucose levels in the Output:	The effect was not lost on sensitivity analysis . Subgroup analyses suggest greater effects in studies longer than 3 months , in Western population s , at lower doses , and in studies at lower risk of bias . Soy isoflavone extracts significantly decreased SBP but not DBP in adult humans , and no dose-response relationship was observed .
MS2752	*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 objective of this study was to assess the effect of coenzyme Q10 ( CoQ10 ) as supplementation to conventional antifailure drugs on quality of life and cardiac function in children with chronic heart failure due to dilated cardiomyopathy ( DCM ) . The study was an open-label prospect i ve study performed in two of the largest pediatric centers in Thail and from August 2000 to June 2003 . A total of 15 patients with idiopathic chronic DCM were included , with the median age of 4.4 years ( range , 0.6 - 16.3 ) . Presenting symptoms were congestive heart failure in 12 cases ( 80 % ) , cardiogenic shock in 2 cases ( 13.3 % ) , and cardiac arrhythmia in 1 case ( 6.7 % ) . Sixty-one percent of patients were in the New York Heart Association functional class 2 ( NYHA 2 ) , 31 % in NYHA 3 , and 8 % in NYHA 4 . Cardiothoracic ratio from chest x-ray , left ventricular ejection fraction , and left ventricular end diastolic dimension in echocardiogram were 0.62 ( range , 0.55 - 0.78 ) , 30 % ( range , 20 - 40 ) , and 5.2 cm ( range , 3.8 - 6.5 ) , respectively . CoQ10 was given at a dosage of 3.1 ? 0.6 mg/kg/day for 9 months as a supplementation to a fixed amount of conventional antifailure drugs throughout the study . At follow-up periods of 1 , 3 , 6 , and 9 months , NYHA functional class was significantly improved , as was CT ratio and QRS duration at 3 and 9 months follow-up with CoQ10 when compared to the baseline and post-discontinuation of CoQ10 at 9 months ( range , 4.8 - 10.8 ) . However , when multiple comparisons were taken into consideration , there was no statistical significant improvement . In addition to the conventional antifailure drugs , CoQ10 may improve NYHA class and CT ratio and shorten ventricular depolarization in children with chronic idiopathic DCM BACKGROUND The number of patients awaiting heart transplantation is increasing in proportion to the waiting period for a donor . Studies have shown that coenzyme Q10 ( CoQ10 ) has a beneficial effect on patients with heart failure . HYPOTHESIS The purpose of the present double-blind , placebo-controlled , r and omized study was to assess the effect of CoQ10 on patients with end-stage heart failure and to determine if CoQ10 can improve the pharmacological bridge to heart transplantation . METHODS A prospect i ve double-blind design was used . Thirty-two patients with end-stage heart failure awaiting heart transplantation were r and omly allocated to receive either 60 mg U/day of Ultrasome -- CoQ10 ( special preparation to increase intestinal absorption ) or placebo for 3 months . All patients continued their regular medication regimen . Assessment s included anamnesis with an extended question naire based partially on the Minnesota Living with Heart Failure Question naire , 6-min walk test , blood tests for atrial natriuretic factor ( ANF ) and tumor necrosis factor ( TNF ) , and echocardiography . RESULTS Twenty-seven patients completed the study . The study group showed significant improvement in the 6-min walk test and a decrease in dyspnea , New York Heart Association ( NYHA ) classification , nocturia , and fatigue . No significant changes were noted after 3 months of treatment in echocardiography parameters ( dimensions and contractility of cardiac chambers ) or ANF and TNF blood levels . CONCLUSIONS The administration of CoQ10 to heart transplant c and i date s led to a significant improvement in functional status , clinical symptoms , and quality of life . However , there were no objective changes in echo measurements or ANF and TNF blood levels . Coenzyme Q10 may serve as an optional addition to the pharmacologic armamentarium of patients with end-stage heart failure . The apparent discrepancy between significant clinical improvement and unchanged cardiac status requires further investigation Despite major advances in treatment congestive heart failure ( CHF ) is still one of the major causes of morbidity and mortality . Coenzyme Q10 is a naturally occurring substance that has antioxidant and membrane stabilizing properties . Administration of coenzyme Q10 in conjunction with st and ard medical therapy has been reported to augment myocardial kinetics , increase cardiac output , elevate the ischemic threshold , and enhance functional capacity in patients with congestive heart failure . The aim of this study was to investigate some of these cl aims . Seventeen patients ( mean New York Heart Association functional class 3.0 ± 0.4 ) were enrolled in an open-label study . After 4 months of coenzyme Q10 , therapy , functional class improved 20 % ( 3.0 ± 0.4 to 2.4 ± 0.6 , p < 0.001 ) and there was a 27 % improvement in mean CHF score ( 2.8 ± 0.4 to 2.2 ± 0.4 , p < 0.001 ) . Percent change in the resting variables included the following : left ventricular ejection fraction ( LVEF ) , + 34.8 % ; cardiac output , + 15.7 % ; stroke volume index , + 18.9 % ; end-diastolic volume area , −8.4 % ; systolic blood pressure ( SBP ) , −4.4 % ; and Emax , ( SBP end-systolic volume index [ ESVI ] ) + 11.7 % . MVo2 decreased by 5.3 % ( 31.9 ± 2.6 to 30.2 ± 2.4 , p = NS ) . Therapy with coenzyme Q10 was associated with a mean 25.4 % increase in exercise duration and a 14.3 % increase in workload . Percent changes after therapy include the following : exercise LVEF , + 24.6 % ; cardiac output , + 19.1 % ; stroke volume index , + 13.2 % ; heart rate , + 6.5 % ; SBP , −4.3 % ; SBP ESVI , + 18.6 % ; end-diastolic volume ( EDV ) area , −6.0 % ; MVo2 , −7.0 % ; and ventricular compliance ( % δ SV EDV ) improved < 100 % . In summary , coenzyme Q10 therapy is associated with significant functional , clinical , and hemodynamic improvements within the context of an extremely favorable benefit-to-risk ratio . Coenzyme Q10 enhances cardiac output by exerting a positive inotropic effect upon the myocardium as well as mild vasodilatation The long-term efficacy and safety of HMG-CoA reductase inhibitors ( statins ) have been established in large multicenter trials . Inhibition of this enzyme , however , results in decreased synthesis of cholesterol and other products downstream of mevalonate , such as CoQ10 or dolichol . This was a r and omized double-blind , placebo-controlled study that examined the effects of CoQ10 and placebo in hypercholesterolemic patients treated by atorvastatin . Eligible patients were given 10mg/day of atorvastatin for 16 weeks . Half of the patients ( n=24 ) were supplemented with 100mg/day of CoQ10 , while the other half ( n=25 ) were given the placebo . Serum LDL-C levels in the CoQ10 group decreased by 43 % , while in the placebo group by 49 % . The HDL-C increment was more striking in the CoQ10 group than in the placebo group . All patients showed definite reductions of plasma CoQ10 levels in the placebo group , by 42 % . All patients supplemented with CoQ10 showed striking increases in plasma CoQ10 by 127 % . In conclusion atorvastatin definitely decreased plasma CoQ10 levels and supplementation with CoQ10 increased their levels . These changes in plasma CoQ10 levels showed no relation to the changes in serum AST , ALT and CK levels . Further studies are needed , however , for the evaluation of CoQ10 supplementation in statin therapy OBJECTIVES The aim of this study was to evaluate the relationship between plasma oxidized low-density lipoprotein ( oxLDL ) , a marker of oxidative stress , and the prognosis of patients with chronic congestive heart failure ( CHF ) . BACKGROUND Oxidative stress appears to play a role in the pathophysiology of CHF . We have recently reported the usefulness of plasma oxLDL as a marker of oxidative stress in CHF patients with dilated cardiomyopathy . METHODS We measured the plasma level of oxLDL by s and wich enzyme-linked immunosorbent assay using a specific monoclonal antibody against oxLDL in 18 age-matched normal subjects and in 84 patients with chronic CHF ( New York Heart Association functional class II to IV ) and monitored them prospect ively for a mean follow-up period of 780 days . RESULTS Plasma oxLDL level was significantly higher in severe CHF patients than in control subjects and mild CHF patients . A significant negative correlation existed between the plasma level of oxLDL and left ventricular ejection fraction ( LVEF ) and a significant positive correlation between the plasma level of oxLDL and plasma norepinephrine level . Twenty-six patients had cardiac events ; 14 had cardiac death and 12 were hospitalized for heart failure or other cardiovascular events . Among 10 variables including LVEF and neurohumoral factors , only high plasma levels of brain natriuretic peptide and oxLDL were shown to be independent predictors of mortality . CONCLUSIONS These results indicate that the plasma level of oxLDL is a useful predictor of mortality in patients with CHF , suggesting that oxidative stress plays an important role in the pathophysiology of CHF There are numerous reasons to believe that deficiency of coenzyme Q10 ( ubiquinone ) may exacerbate the poor contractility of myocardial cells in patients with heart failure . Not only does coenzyme Q10 play a central role in mitochondrial oxidative phosphorylation ( 1 ) , but it may also act as an antioxidant scavenger ( 2 ) . Because the myocardium of patients with congestive heart failure demonstrates oxidative stress ( 3 ) and coenzyme Q10 prevents lipid peroxidation ( 4 ) , this substance conceivably could prevent myocardial destruction . Furthermore , the concentration of coenzyme Q10 is decreased in myocardial cells of patients with advanced heart failure ( 5 ) , and the extent of myocardial coenzyme Q10 deficiency correlates with the clinical severity of heart failure ( 5 , 6 ) . It is thus not surprising that nutritional supplementation with coenzyme Q10 has been proposed as a treatment for congestive heart failure , that it is extensively advertised , and that it is commonly used by patients with this condition . Many small studies have been published , but most were uncontrolled and unblinded . Approximately 31 Japanese clinical reports describe favorable effects with intravenous or oral coenzyme Q10 ( 7 ) . The studies involved only a small number of patients with heart failure and tended to include patients with cardiac disease of various causes . Nevertheless , in 1974 the Japanese government approved marketing of coenzyme Q10 for the treatment of heart failure . The few U.S. and European studies have had conflicting results . Some controlled studies showed no effect ( 8 , 9 ) , but their limitations make the results inconclusive . Other trials noted improvement ( 10 - 13 ) , but concerns about end points , small numbers of patients , and the lack of blinding have limited the acceptance of these studies . With such conflicting data , r and omized , controlled , and blinded studies are needed to test the hypothesis that patients with advanced heart failure are deficient in coenzyme Q10 and that oral supplementation with coenzyme Q10 results in clinical improvement . We therefore evaluated the effects of coenzyme Q10 supplementation on left ventricular ejection fraction and exercise tolerance in patients with symptomatic heart failure despite st and ard medical therapy . Methods We performed a r and omized , double-blind , placebo-controlled trial to compare the effects of oral coenzyme Q10 ( 200 mg/d ) and placebo . The two primary end points were change in ejection fraction , as assessed by nuclear ventriculography , and change in peak oxygen consumption . The study protocol was approved by the human volunteers committee of the University of Maryl and School of Medicine . Inclusion and Exclusion Criteria Patients with New York Heart Association functional class III or IV disease were eligible for inclusion in this study . All patients had ejection fractions less than 40 % ( documented by radionuclide ventriculography ) and maximal oxygen consumption less than 17.0 mL/kg of body weight per minute or less than 50 % of the predicted value . These criteria were used to select symptomatic patients who would have the potential to improve . The mean peak oxygen consumption in our patients was 13.1 mL/kg per minute . In comparison , the peak oxygen consumption criterion for cardiac transplantation is generally considered to be less than 14.0 mL/kg per minute , and the mean peak oxygen consumption in nonexercising normal elderly persons ( mean age , 67 years ) has been reported to be 19.0 mL/kg per minute ( 14 ) . Patients were required to have been receiving an unchanged medical regimen for at least 1 month . Patients who had previously taken coenzyme Q10 were excluded . Baseline Testing At baseline , three procedures were performed . First , a grade d symptom-limited cardiopulmonary exercise test using the Naughton protocol was conducted to assess maximal oxygen consumption . The test was Output:	RESULT Extracted data for Seven systematic review s for primary outcomes , net changes in cardiac output , cardiac index , New York Heart Association functional classification , improved survival , based on existing evidence , there is a case for use of CoQ10 as an adjunctive therapy in congestive heart failure , especially in those patients unable to tolerate mainstream medical therapies . Evidence suggests that the CoQ10 supplement may be a useful tool for managing patients with heart failure
MS2753	*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 AND OBJECTIVE Sepsis and septic shock are very common conditions among critically ill patients that lead to multiple organ dysfunction syndrome ( MODS ) and death . Our purpose was to investigate the efficacy of early administration of dexamethasone for patients with septic shock , with the aim of halting the progression towards MODS and death . DESIGN AND SETTING Prospect i ve , r and omized , double-blind , single-center study , developed in a surgical intensive care unit at Hospital das Clínicas , Faculdade de Medicina da Universidade de São Paulo . METHODS The study involved 29 patients with septic shock . All eligible patients were prospect ively r and omized to receive either a dose of 0.2 mg/kg of dexamethasone ( group D ) or placebo ( group P ) , given three times at intervals of 36 hours . The patients were monitored over a seven-day period by means of the sequential organ failure assessment score . RESULTS Patients treated with dexamethasone did not require vasopressor therapy for as much time over the seven-day period as did the placebo group ( p = 0.043 ) . Seven-day mortality was 67 % in group P ( 10 out of 15 ) and 21 % in group D ( 3 out of 14 ) ( relative risk = 0.31 , 95 % confidence interval 0.11 to 0.88 ) . Dexamethasone enhanced the effects of vasopressor drugs . CONCLUSIONS Early treatment with dexamethasone reduced the seven-day mortality among septic shock patients and showed a trend towards reduction of 28-day mortality BACKGROUND Septic shock is characterized by dysregulation of the host response to infection , with circulatory , cellular , and metabolic abnormalities . We hypothesized that therapy with hydrocortisone plus fludrocortisone or with drotrecogin alfa ( activated ) , which can modulate the host response , would improve the clinical outcomes of patients with septic shock . METHODS In this multicenter , double‐blind , r and omized trial with a 2‐by‐2 factorial design , we evaluated the effect of hydrocortisone‐plus‐fludrocortisone therapy , drotrecogin alfa ( activated ) , the combination of the three drugs , or their respective placebos . The primary outcome was 90‐day all‐cause mortality . Secondary outcomes included mortality at intensive care unit ( ICU ) discharge and hospital discharge and at day 28 and day 180 and the number of days alive and free of vasopressors , mechanical ventilation , or organ failure . After drotrecogin alfa ( activated ) was withdrawn from the market , the trial continued with a two‐group parallel design . The analysis compared patients who received hydrocortisone plus fludrocortisone with those who did not ( placebo group ) . RESULTS Among the 1241 patients included in the trial , the 90‐day mortality was 43.0 % ( 264 of 614 patients ) in the hydrocortisone‐plus‐fludrocortisone group and 49.1 % ( 308 of 627 patients ) in the placebo group ( P=0.03 ) . The relative risk of death in the hydrocortisone‐plus‐fludrocortisone group was 0.88 ( 95 % confidence interval , 0.78 to 0.99 ) . Mortality was significantly lower in the hydrocortisone‐plus‐fludrocortisone group than in the placebo group at ICU discharge ( 35.4 % vs. 41.0 % , P=0.04 ) , hospital discharge ( 39.0 % vs. 45.3 % , P=0.02 ) , and day 180 ( 46.6 % vs. 52.5 % , P=0.04 ) but not at day 28 ( 33.7 % and 38.9 % , respectively ; P=0.06 ) . The number of vasopressor‐free days to day 28 was significantly higher in the hydrocortisone‐plus‐fludrocortisone group than in the placebo group ( 17 vs. 15 days , P<0.001 ) , as was the number of organ‐failure – free days ( 14 vs. 12 days , P=0.003 ) . The number of ventilator‐free days was similar in the two groups ( 11 days in the hydrocortisone‐plus‐fludrocortisone group and 10 in the placebo group , P=0.07 ) . The rate of serious adverse events did not differ significantly between the two groups , but hyperglycemia was more common in hydrocortisone‐plus‐fludrocortisone group . CONCLUSIONS In this trial involving patients with septic shock , 90‐day all‐cause mortality was lower among those who received hydrocortisone plus fludrocortisone than among those who received placebo . ( Funded by Programme Hospitalier de Recherche Clinique 2007 of the French Ministry of Social Affairs and Health ; APROCCHSS Clinical Trials.gov number , NCT00625209 . Background Authors of recent meta-analyses have reported that prolonged glucocorticoid treatment is associated with significant improvements in patients with severe pneumonia or acute respiratory distress syndrome ( ARDS ) of multifactorial etiology . A prospect i ve r and omized trial limited to patients with sepsis-associated ARDS is lacking . The objective of our study was to evaluate the efficacy of hydrocortisone treatment in sepsis-associated ARDS . Methods In this double-blind , single-center ( Siriraj Hospital , Bangkok ) , r and omized , placebo-controlled trial , we recruited adult patients with severe sepsis within 12 h of their meeting ARDS criteria . Patients were r and omly assigned ( 1:1 ratio ) to receive either hydrocortisone 50 mg every 6 h or placebo . The primary endpoint was 28-day all-cause mortality ; secondary endpoints included survival without organ support on day 28 . Results Over the course of 4 years , 197 patients were r and omized to either hydrocortisone ( n = 98 ) or placebo ( n = 99 ) and were included in this intention-to-treat analysis . The treatment group had significant improvement in the ratio of partial pressure of oxygen in arterial blood to fraction of inspired oxygen and lung injury score ( p = 0.01 ) , and similar timing to removal of vital organ support ( HR 0.74 , 95 % CI 0.51–1.07 ; p = 0.107 ) . After adjustment for significant covariates , day 28 survival was similar for the whole group ( HR 0.80 , 95 % CI 0.46–1.41 ; p = 0.44 ) and for the larger subgroup ( n = 126 ) with Acute Physiology and Chronic Health Evaluation II score < 25 ( HR 0.57 , 95 % CI 0.24–1.36 ; p = 0.20 ) . With the exception of hyperglycemia ( 80.6 % vs. 67.7 % ; p = 0.04 ) , the rate of adverse events was similar . Hyperglycemia had no impact on outcome . Conclusions In sepsis-associated ARDS , hydrocortisone treatment was associated with a significant improvement in pulmonary physiology , but without a significant survival benefit . Trial registration Clinical Trials.gov identifier NCT01284452 . Registered on 18 January 2011 Background Recent studies have reported a high prevalence of relative adrenal insufficiency in patients with liver cirrhosis . However , the effect of corticosteroid replacement on mortality in this high-risk group remains unclear . We examined the effect of low-dose hydrocortisone in patients with cirrhosis who presented with septic shock . Methods We enrolled patients with cirrhosis and septic shock aged 18 years or older in a r and omized double-blind placebo-controlled trial . Relative adrenal insufficiency was defined as a serum cortisol increase of less than 250 nmol/L or 9 μg/dL from baseline after stimulation with 250 μg of intravenous corticotropin . Patients were assigned to receive 50 mg of intravenous hydrocortisone or placebo every six hours until hemodynamic stability was achieved , followed by steroid tapering over eight days . The primary outcome was 28-day all-cause mortality . Results The trial was stopped for futility at interim analysis after 75 patients were enrolled . Relative adrenal insufficiency was diagnosed in 76 % of patients . Compared with the placebo group ( n = 36 ) , patients in the hydrocortisone group ( n = 39 ) had a significant reduction in vasopressor doses and higher rates of shock reversal ( relative risk [ RR ] 1.58 , 95 % confidence interval [ CI ] 0.98–2.55 , p = 0.05 ) . Hydrocortisone use was not associated with a reduction in 28-day mortality ( RR 1.17 , 95 % CI 0.92–1.49 , p = 0.19 ) but was associated with an increase in shock relapse ( RR 2.58 , 95 % CI 1.04–6.45 , p = 0.03 ) and gastrointestinal bleeding ( RR 3.00 , 95 % CI 1.08–8.36 , p = 0.02 ) . Interpretation Relative adrenal insufficiency was very common in patients with cirrhosis presenting with septic shock . Despite initial favourable effects on hemodynamic parameters , hydrocortisone therapy did not reduce mortality and was associated with an increase in adverse effects . ( Current Controlled Trials registry no. IS RCT N99675218 . BACKGROUND In sub-Saharan Africa , bacterial meningitis is common and is associated with a high mortality . Adjuvant therapy with corticosteroids reduces mortality among adults in the developed world , but it has not been adequately tested in developing countries or in the context of advanced human immunodeficiency virus ( HIV ) infection . METHODS We conducted a r and omized , double-blind , placebo-controlled trial of dexamethasone ( 16 mg twice daily for 4 days ) and an open-label trial of intramuscular versus intravenous ceftriaxone ( 2 g twice daily for 10 days ) in adults with an admission diagnosis of bacterial meningitis in Blantyre , Malawi . The primary outcome was death at 40 days after r and omization . RESULTS A total of 465 patients , 90 % of whom were HIV-positive , were r and omly assigned to receive dexamethasone ( 233 patients ) or placebo ( 232 patients ) plus intramuscular ceftriaxone ( 230 patients ) or intravenous ceftriaxone ( 235 patients ) . There was no significant difference in mortality at 40 days in the corticosteroid group ( 129 of 231 patients ) as compared with the placebo group ( 120 of 228 patients ) by intention-to-treat analysis ( odds ratio , 1.14 ; 95 % confidence interval [ CI ] , 0.79 to 1.64 ) or when the analysis was restricted to patients with proven pneumococcal meningitis ( 68 of 129 patients receiving corticosteroids vs. 72 of 143 patients receiving placebo ) ( odds ratio , 1.10 ; 95 % CI , 0.68 to 1.77 ) . There were no significant differences between groups in the outcomes of disability and death combined , hearing impairment , and adverse events . There was no difference in mortality with intravenous ceftriaxone ( 121 of 230 patients ) as compared with intramuscular ceftriaxone ( 128 of 229 patients ) ( odds ratio , 0.88 ; 95 % CI , 0.61 to 1.27 ) . CONCLUSIONS Adjuvant therapy with dexamethasone for bacterial meningitis in adults from an area with a high prevalence of HIV did not reduce mortality or morbidity . In this setting , intramuscular administration was not inferior to intravenous administration of ceftriaxone for bacterial meningitis . ( Current Controlled Trials number , IS RCT N31371499 [ controlled-trials.com ] . ) Introduction The aim of the study was to assess the prognostic importance of basal cortisol concentrations and cortisol response to corticotropin , and to determine the effects of physiological dose steroid therapy on mortality in patients with sepsis . Methods Basal cortisol level and corticotropin stimulation test were performed within 24 hours in all patients . One group ( 20 patients ) received st and ard therapy for sepsis and physiological-dose steroid therapy for 10 days ; the other group ( 20 patients ) received only st and ard therapy for sepsis . Basal cortisol level was measured on the 14th day in patients who recovered . The outcome of sepsis was compared . Results Only Sequential Organ Failure Assessment ( SOFA ) score was found related to mortality , independent from other factors in multivariate analysis . No significant difference was found between the changes in the percentage of SOFA scores of the steroid therapy group and the st and ard therapy group in survivors , nor between the groups in basal and peak cortisol levels , cortisol response to corticotropin test and mortality . The mortality rates among patients with occult Output:	Conclusions and Relevance The findings suggest that administration of corticosteroids is associated with reduced 28-day mortality compared with placebo use or st and ard supportive care .
MS2754	*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 — Statins reduce the rate of major cardiovascular events in high-risk patients , but their potential benefit as treatment for heart failure ( HF ) is less clear . Methods and Results — Patients ( n=10 001 ) with stable coronary disease were r and omized to treatment with atorvastatin 80 or 10 mg/d and followed up for a median of 4.9 years . A history of HF was present in 7.8 % of patients . A known ejection fraction < 30 % and advanced HF were exclusion criteria for the study . A predefined secondary end point of the study was hospitalization for HF . The incidence of hospitalization for HF was 2.4 % in the 80-mg arm and 3.3 % in the 10-mg arm ( hazard ratio , 0.74 ; 95 % confidence interval , 0.59 to 0.94 ; P=0.0116 ) . The treatment effect of the higher dose was more marked in patients with a history of HF : 17.3 % versus 10.6 % in the 10- and 80-mg arms , respectively ( hazard ratio , 0.59 ; 95 % confidence interval , 0.4 to 0.88 ; P=0.009 ) . Among patients without a history of HF , the rates of hospitalization for HF were much lower : 1.8 % in the 80-mg group and 2.0 % in the 10-mg group ( hazard ratio , 0.87 ; 95 % confidence interval , 0.64 to 1.16 ; P=0.34 ) . Only one third of patients hospitalized for HF had evidence of preceding angina or myocardial infa rct ion during the study period . Blood pressure was almost identical during follow-up in the treatment groups . Conclusions — Compared with a lower dose , intensive treatment with atorvastatin in patients with stable coronary disease significantly reduces hospitalizations for HF . In a post hoc analysis , this benefit was observed only in patients with a history of HF . The mechanism accounting for this benefit is unlikely to be due primarily to a reduction in interim coronary events or differences in blood pressure BACKGROUND We previously reported urinary podocytes to be a marker of glomerular injury . The aim of the present study was to determine whether cerivastatin , a newly developed , potent synthetic statin , affects proteinuria and urinary podocyte excretion in patients with chronic glomerulonephritis ( CGN ) . METHODS We r and omly assigned 40 normotensive hypercholesterolemic patients with CGN to receive either cerivastatin 0.15 mg/day ( n=20 ) or placebo ( n=20 ) . Subjects comprised 24 men and 16 women , with a mean age of 40.8+/-14.4 years ; 27 had IgA nephropathy and 13 had non-IgA proliferative glomerulonephritis . Treatment was continued for 6 months . Plasma total cholesterol , HDL-cholesterol , LDL-cholesterol and triglycerides , urinary protein excretion and the number of podocytes were measured before treatment and at 3 and 6 months after treatment . RESULTS After 6 months , a significant reduction in total cholesterol ( P<0.001 ) , LDL-cholesterol ( P<0.001 ) and triglycerides ( P<0.05 ) , and a significant increase in HDL-cholesterol ( P<0.001 ) were observed in the group treated with cerivastatin . Urinary protein excretion decreased from 1.8+/-0.6 to 0.8+/-0.4 g/day , ( P<0.01 ) in this group , and urinary podocyte excretion decreased from 1.6+/-0.6 to 0.9+/-0.4 cells/ml ( P<0.01 ) . However , placebo showed little effect on these lipid levels , urinary protein excretion and urinary podocyte excretion . The differences between the cerivastatin group and the placebo group were significant ( cholesterol , P<0.001 ; LDL-cholesterol , P<0.001 ; triglycerides , P<0.05 ; HDL-cholesterol , P<0.001 ; urinary protein , P<0.01 ; and urinary podocytes , P<0.01 ) . CONCLUSION Statins such as cerivastatin may be beneficial for restoration of injured podocytes in patients with CGN and hypercholesterolaemia BACKGROUND The effects of cholesterol-lowering treatment with statins on mortality and risk of cancer beyond the usual 5 - 6-year trial periods are unknown . We extended post-trial follow-up of participants in the Sc and inavian Simvastatin Survival Study ( 4S ) to investigate cause-specific mortality and incidence of cancer 5 years after closure of the trial . METHODS 4S was a r and omised double-blind trial of simvastatin or placebo in patients with coronary heart disease , serum total cholesterol 5.5 - 8.0 mmol/L , and serum triglycerides 2.5 mmol/L or lower . The double-blind period lasted for a median of 5.4 years ( range for survivors 4.9 - 6.3 ) and ended in 1994 . After the trial , most patients in both groups received open-label lipid-lowering treatment . National registers were used to assess mortality and causes of death and cancer incidence in the original treatment groups for a median total follow-up time of 10.4 years ( range for survivors 9.9 - 11.3 ) . Analysis was by intention to treat . FINDINGS 414 patients originally allocated simvastatin and 468 assigned placebo died during the 10.4-year follow-up ( relative risk 0.85 [ 95 % CI 0.74 - 0.97 ] , p=0.02 ) , a difference largely attributable to lower coronary mortality in the simvastatin group ( 238 vs 300 deaths ; 0.76 [ 0.64 - 0.90 ] , p=0.0018 ) . 85 cancer deaths arose in the simvastatin group versus 100 in the placebo group ( 0.81 [ 0.60 - 1.08 ] , p=0.14 ) , and 227 incident cancers were reported in the simvastin group versus 248 in the placebo group ( 0.88 [ 0.73 - 1.05 ] , p=0.15 ) . Incidence of any specific type of cancer did not rise in the simvastatin group . INTERPRETATION Simvastatin treatment for 5 years in a placebo-controlled trial , followed by open-label statin therapy , was associated with survival benefit over 10 years of follow-up compared with open-label statin therapy for the past 5 years only . No difference was noted in mortality from and incidence of cancer between the original simvastatin group and placebo group BACKGROUND The PREVEND IT investigated whether treatment targeted at lowering urinary albumin excretion ( UAE ) would reduce adverse cardiovascular events . We obtained extended follow-up data to approximately 10 years to investigate the long-term effects of fosinopril 20 mg and pravastatin 40 mg on cardiovascular outcomes in subjects with UAE > 15 mg per 24 hours . METHODS The original PREVEND IT consisted of 864 participants and 839 survivors after 4 years . For every survivor , the primary end point determined by the combined incidence of cardiovascular mortality and hospitalization for cardiovascular morbidity was registered in several national data bases and electronic hospital systems . RESULTS Mean total follow-up of the extended PREVEND IT was 9.5 years ( range 9.4 - 10.7 years ) . Four years of treatment with fosinopril was not associated with a reduction in the primary end point compared with placebo ( hazard ratio 0.87 , 95 % CI 0.61 - 1.24 [ P = .42 ] ) during long-term follow-up . After 9.5 years , subjects with a baseline UAE in the upper quintile ( > 50 mg/24 hours ) had a total event rate of 29.5 % and were at a higher risk for developing cardiovascular disease compared with less UAE ( hazard ratio 2.03 , 95 % CI 1.38 - 2.97 [ P ≤ .01 ] ) . In addition , 4 years of fosinopril treatment result ed in a risk reduction of 45 % ( 95 % CI 6%-75 % [ P = .04 ] ) in this group compared with placebo . Subjects originally assigned to pravastatin had no overall risk reduction in the primary end point ( P = .99 ) . CONCLUSIONS Elevated UAE is associated with increased cardiovascular mortality and morbidity after 9.5 years of follow-up , with a doubling of the risk if the UAE is > 50 mg per 24 hours . In this group , the benefits of 4-year treatment with fosinopril were sustained during posttrial follow-up for cardiovascular mortality and morbidity . We propose that UAE be used to estimate risk in the general population and that large clinical trials be design ed to confirm the hypothesis that angiotensin-converting enzyme-inhibitor treatment may be beneficial in patients with mildly elevated UAE despite the absence of other comorbidities Aims Patients with Type 2 diabetes have an elevated risk of stroke . The role of lipid levels and diabetes‐specific factors in risk prediction of stroke is unclear , and estimates of efficacy of lipid‐lowering therapy vary between trials . We examined predictors of stroke and the effect of atorvastatin on specific stroke subtypes in Type 2 diabetes in the Collaborative Atorvastatin Diabetes Study ( CARDS ) [ a trial of 2838 participants with mean low‐density lipoprotein cholesterol < 4.14 mmol/l , no history of macrovascular disease and r and omized to atorvastatin 10 mg daily or placebo ] Background —Therapeutic decisions regarding pharmacological therapy should be based on safety and tolerability as well as efficacy data . Clinical trials design ed to assess efficacy are often insufficiently powered to generate reliable safety data . Methods and Results —The West of Scotl and Coronary Prevention Study ( WOSCOPS ) , the Cholesterol and Recurrent Events ( CARE ) , and Long-term Intervention with Pravastatin in Ischemic Disease ( LIPID ) studies collectively accumulated > 112 000 person-years of exposure in double-blind r and omized trials comparing placebo and pravastatin ( 40 mg once daily ) . During 5 years of exposure , the incidence of fatal and nonfatal cancers was similar between pravastatin and placebo groups . No differences in noncardiovascular serious adverse events were detected . With > 243 000 blood sample analyses , the percentage of patients with any abnormal liver function test after baseline sampling was similar ( > 3 × the upper limit of normal for alanine aminotransferase : 128 [ 1.4 % ] versus 131 [ 1.4 % ] patients for pravastatin versus placebo , respectively ) . Study medication was withdrawn in 3 pravastatin and 7 placebo patients due to creatine phosphokinase elevations ; no cases of mild or severe myopathy were reported . A Cox regression model considering treatment group , age , diabetes , smoking , whether primary or secondary prevention study , and cardiovascular serious adverse events indicates that the likelihood of discontinuing pravastatin was less than placebo . Conclusions —This prospect i ve analysis indicates that during prolonged exposure , 40 mg of pravastatin is well tolerated , with no excess of noncardiovascular serious adverse events , including liver function abnormalities and laboratory and clinical evidence for myositis . These extensive safety and tolerability data provide important information for therapeutic decisions regarding this pharmacological agent BACKGROUND Although patients with chronic kidney disease ( CKD ) are at increased risk of cardiovascular disease ( CVD ) , the roles of lipid-modifying therapies in decreasing CVD risk are unclear . Our aim is to compare the effects of statin and fibrate therapy on arterial function as a risk marker of CVD . STUDY DESIGN Double-blind , r and omized , placebo-controlled , parallel-group study . SETTING & PARTICIPANTS Ambulatory patients with stages 3 to 5 CKD . INTERVENTION 6 weeks of atorvastatin , 40 mg/d , or gemfibrozil , 600 mg twice daily , with placebo . OUTCOMES & MEASUREMENTS Primary outcome was arterial function assessed by means of endothelial-dependent flow-mediated dilatation ( FMD ) and small-artery compliance ( C2 ) . Secondary outcomes included endothelial-independent glyceryl trinitrate-mediated dilatation ( GTNMD ) , large-artery compliance ( C1 ) , and levels of lipids , lipoproteins , and oxidized low-density lipoprotein , as well as markers of insulin resistance and inflammation . RESULTS Compared with placebo , atorvastatin significantly decreased low-density lipoprotein ( -52 % ) , triglyceride ( -30 % ) , and oxidized low-density lipoprotein levels ( -41 % ; P < 0.0001 ) . Gemfibrozil significantly decreased triglyceride levels ( -40 % ) and increased high-density lipoprote Output:	Statins had uncertain effects on stroke ( 5 studies , 8658 participants ; RR 0.62 , 95 % CI 0.35 to 1.12).Potential harms from statin therapy were limited by lack of systematic reporting and were uncertain in analyses that had few events : elevated creatine kinase ( 7 studies , 4514 participants ; RR 0.84 , 95 % CI 0.20 to 3.48 ) , liver function abnormalities ( 7 studies , RR 0.76 , 95 % CI 0.39 to 1.50 ) , withdrawal due to adverse events ( 13 studies , 4219 participants ; RR 1.16 , 95 % CI 0.84 to 1.60 ) , and cancer ( 2 studies , 5581 participants ; RR 1.03 , 95 % CI 0.82 to 130).Statins had uncertain effects on progression of CKD . Statins clearly reduced risks of death , major cardiovascular events , and MI in people with CKD who did not have CVD at baseline ( primary prevention ) . Statins consistently lower death and major cardiovascular events by 20 % in people with CKD not requiring dialysis . Statin-related effects on stroke and kidney function were found to be uncertain and adverse effects of treatment are incompletely understood . Statins have an important role in primary prevention of cardiovascular events and mortality in people who have CKD
MS2755	*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 In metastatic colorectal cancer , phase III studies have demonstrated the superiority of fluorouracil ( FU ) with leucovorin ( LV ) in combination with irinotecan or oxaliplatin over FU + LV alone . This phase III study investigated two sequences : folinic acid , FU , and irinotecan ( FOLFIRI ) followed by folinic acid , FU , and oxaliplatin ( FOLFOX6 ; arm A ) , and FOLFOX6 followed by FOLFIRI ( arm B ) . PATIENTS AND METHODS Previously untreated patients with assessable disease were r and omly assigned to receive a 2-hour infusion of l-LV 200 mg/m(2 ) or dl-LV 400 mg/m(2 ) followed by a FU bolus 400 mg/m(2 ) and 46-hour infusion 2,400 to 3,000 mg/m(2 ) every 46 hours every 2 weeks , either with irinotecan 180 mg/m(2 ) or with oxaliplatin 100 mg/m(2 ) as a 2-hour infusion on day 1 . At progression , irinotecan was replaced by oxaliplatin ( arm A ) , or oxaliplatin by irinotecan ( arm B ) . RESULT Median survival was 21.5 months in 109 patients allocated to FOLFIRI then FOLFOX6 versus 20.6 months in 111 patients allocated to FOLFOX6 then FOLFIRI ( P = .99 ) . Median second progression-free survival ( PFS ) was 14.2 months in arm A versus 10.9 in arm B ( P = .64 ) . In first-line therapy , FOLFIRI achieved 56 % response rate ( RR ) and 8.5 months median PFS , versus FOLFOX6 which achieved 54 % RR and 8.0 months median PFS ( P = .26 ) . Second-line FOLFIRI achieved 4 % RR and 2.5 months median PFS , versus FOLFOX6 which achieved 15 % RR and 4.2 months PFS . In first-line therapy , National Cancer Institute Common Toxicity Criteria grade 3/4 mucositis , nausea/vomiting , and grade 2 alopecia were more frequent with FOLFIRI , and grade 3/4 neutropenia and neurosensory toxicity were more frequent with FOLFOX6 . CONCLUSION Both sequences achieved a prolonged survival and similar efficacy . The toxicity profiles were different BACKGROUND In the non-curative setting , the sequence in which anticancer agents are used , singly or in combination , may be important if patients are to receive the maximum period of disease control with the minimum of adverse effects . We compared sequential and combination chemotherapy strategies in patients with unpretreated advanced or metastatic colorectal cancer , who were regarded as not potentially curable irrespective of response . METHODS We studied patients with advanced colorectal cancer , starting treatment with non-curative intent . 2135 unpretreated patients were r and omly assigned to three treatment strategies in the ratio 1:1:1 . Strategy A ( control group ) was single-agent fluorouracil ( given with levofolinate over 48 h every 2 weeks ) until failure , then single-agent irinotecan . Strategy B was fluorouracil until failure , then combination chemotherapy . Strategy C was combination chemotherapy from the outset . Within strategies B and C , patients were r and omly assigned to receive , as the combination regimen , fluorouracil plus irinotecan ( groups B-ir and C-ir ) or fluorouracil plus oxaliplatin ( groups B-ox and C-ox ) . The primary endpoint was overall survival , analysed by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N 79877428 . RESULTS Median survival of patients allocated to control strategy A was 13.9 months . Median survival of each of the other groups was longer ( B-ir 15.0 , B-ox 15.2 , C-ir 16.7 , and C-ox 15.4 months ) . However , log-rank comparison of each group against control showed that only C-ir -- the first-line combination strategy including irinotecan -- satisfied the statistical test for superiority ( p=0.01 ) . Overall comparison of strategy B with strategy C was within the predetermined non-inferiority boundary of HR=1.18 or less ( HR=1.06 , 90 % CI 0.97 - 1.17 ) . INTERPRETATION Our data challenge the assumption that , in this non-curative setting , maximum tolerable treatment must necessarily be used first-line . The staged approach of initial single-agent treatment up grade d to combination when required is not worse than first-line combination , and is an alternative option for discussion with patients This study evaluates the efficacy of capecitabine using data from a large , well-characterised population of patients with metastatic colorectal cancer ( mCRC ) treated in two identically design ed phase III studies . A total of 1207 patients with previously untreated mCRC were r and omised to either oral capecitabine ( 1250 mg m−2 twice daily , days 1−14 every 21 days ; n=603 ) or intravenous ( i.v . ) bolus 5-fluorouracil/leucovorin ( 5-FU/LV ; Mayo Clinic regimen ; n=604 ) . Capecitabine demonstrated a statistically significant superior response rate compared with 5-FU/LV ( 26 vs 17 % ; P<0.0002 ) . Subgroup analysis demonstrated that capecitabine consistently result ed in superior response rates ( P<0.05 ) , even in patient subgroups with poor prognostic indicators . The median time to response and duration of response were similar and time to progression ( TTP ) was equivalent in the two arms ( hazard ratio ( HR ) 0.997 , 95 % confidence interval ( CI ) 0.885–1.123 , P=0.95 ; median 4.6 vs 4.7 months with capecitabine and 5-FU/LV , respectively ) . Multivariate Cox regression analysis identified younger age , liver metastases , multiple metastases and poor Karnofsky Performance Status as independent prognostic indicators for poor TTP . Overall survival was equivalent in the two arms ( HR 0.95 , 95 % CI 0.84–1.06 , P=0.48 ; median 12.9 vs 12.8 months , respectively ) . Capecitabine results in superior response rate , equivalent TTP and overall survival , an improved safety profile and improved convenience compared with i.v . 5-FU/LV as first-line treatment for MCRC . For patients in whom fluoropyrimidine monotherapy is indicated , capecitabine should be strongly considered . Following encouraging results from phase I and II trials , r and omised trials are evaluating capecitabine in combination with irinotecan , oxaliplatin and radiotherapy . Capecitabine is a suitable replacement for i.v . 5-FU as the backbone of colorectal cancer therapy 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 PURPOSE To verify the experience of the GOIM in the treatment of advanced colorectal cancer patients with the FOLFIRI combination therapy . PATIENTS AND METHODS Patients entered in three consecutive trials of the GOIM ( protocol s no. 9706 , 9901 , and 2301 ) were reported in this analysis . A total of 287 chemotherapy-naive patients were treated with FOLFIRI regimen : Irinotecan 180 mg/m(2 ) on day 1 with LV5FU2 regimen ( LV at 100 mg/m(2 ) administered as a 2-hour infusion before FU at 400 mg/m(2 ) as an intravenous bolus injection , and FU at 600 mg/m(2 ) as a 22-hour infusion immediately after 5FU bolus injection on day 1 and 2 ) ; the treatment was repeated every 2 weeks . RESULTS 287 patients entered in these three trials , and 264 ( 92 % ) were evaluable for response . The overall response rate was 34.5 % ( 95 % confidence interval [ CI ] : 29 % to 40 % ) . When only assessable patients were analyzed , overall response rate was 37 % ( 95 % CI : 31 % to 43 % ) . Median time to progression , median duration of response and survival were 7 months , 10.5 months and 14 months , respectively . All but three patients were evaluable for toxicity which was globally mild ; grade 3 - 4 toxicity was uncommon , and gastrointestinal disturbances were the most common . CONCLUSIONS FOLFIRI regimen is effective and well-tolerated as first-line treatment in patients with advanced colorectal cancer . Further studies needed to evaluate the improvement in results with the addition of new drugs to this combination therapy One hundred and ninety-three patients were assigned to receive 5-FU/LV , irinotecan and oxaliplatin in five different sequential treatment groups : Mayo Clinic Regimen ( MCR ) + LV5FU2 ( group A ) ; MCR + irinotecan ( 350 mg/m2 ) ( group B ) ; MCR + FOLFIRI ( group C ) ; MCR + FOLFOX4 ( group D ) ; FOLFIRI + FOLFOX4 ( group E ) . The results were as follows : group A ( 32 patients ) , median overall survival ( OS ) 14 months , median time to progression ( TTP1 ) 6 months , median TTP2 5 months , response rate ( RR1 ) 22 % , RR2 25 % ; group B ( 27 patients ) , OS 11 months , TTP1 6 months , TTP2 3 months , RR1 22 % , RR2 19 % ; group C ( 43 patients ) , OS 14 months , TTP1 5 months , TTP2 5 months , RR1 12 % , RR2 19 % ; group D ( 45 patients ) , OS 15 months , TTP1 5 months , TTP2 4 months , RR1 18 % , RR2 20 % ; group E ( 46 patients ) , OS 19 months , TTP1 9 months , TTP2 5 months , RR1 39 % , RR2 25 % . There was a significant difference in OS ( p < 0.005 ) between groups E vs. B and A , D vs. B. Sequential therapy with 3 active drugs ( FOLFIRI + FOLFOX4 ) was the most efficacious combination in comparison with any other two drug combinations applied in our study This multicenter , Phase II trial was performed to evaluate the antitumor activity and toxicity of irinotecan ( CPT‐11 ) in patients with metastatic colorectal carcinoma that had recurred or progressed after 5‐fluorouracil (5‐FU)‐based chemotherapy BACKGROUND Three different therapeutic regimens of irinotecan ( CPT-11 ) in combination with 5-fluorouracil ( 5-FU ) and folinic acid ( FA ) were evaluated for efficacy and safety in the first-line therapy of advanced colorectal cancer . PATIENTS AND METHODS Patients were r and omly assigned to receive intravenously either : CPT-11 125 mg/m(2 ) , FA 20 mg/m(2 ) followed by 5-FU 500 mg/m(2 ) bolus , weekly for 4 weeks ( arm A , Saltz regimen ) ; or CPT-11 180 mg/m(2 ) day 1 then FA 200 mg/m(2 ) over 2 h and 5-FU 400 mg/m(2 ) bolus and 5-FU 600 mg/m(2 ) 22-h infusion on days 1 and 2 , every 2 weeks ( arm B , Douillard regimen ) ; or CPT-11 350 mg/m(2 ) ( days 1 and 43 ) alternating with FA 20 mg/m(2)/day followed by 5-FU bolus 425 mg/m(2)/day during 5 days ( days 22 - 26 ) ( arm C , Mayo Clinic regimen ) . RESULTS A total of 154 patients were included in the study ( arm A , 51 patients ; arm B , 53 ; arm C , 50 ) . Overall response rates for the intention-to-treat population s were 33 % [ 95 % confidence interval ( CI ) 21 % to 48 % ] , 42 % ( 95 % CI 28 % to 56 % ) and 30 % ( 95 % CI 18 % to 45 % ) for arms A , B and C , respectively . Median times to progression were 6 , 8 and 7 months for arms A , B and C , respectively . Median survival times were 15 , 12 and 17 months for arms A , B and C , respectively . Overall response rates for the evaluable patient population s were 40 % ( 95 % CI 24 % to 58 % ) in arm A Output:	There were higher risks of toxicity outcomes grade 3 or 4 diarrhoea and grade 1 or 2 alopecia , and a lower risk of grade 3 or 4 neutropenia in controls compared to the invervention group . There was no overall survival benefit of the irinotecan and fluoropyrimidine treatment over irinotecan alone , thus both regimens remain reasonable options in treating patients with advanced or metastatic CRC .
MS2756	*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 determine whether a generalizable best- practice individualized behavioral intervention reduced BMI z score relative to st and ard dietetic care among overweight children . METHODS . The design consisted of an assessor-blinded , r and omized , controlled trial involving 134 overweight children ( 59 boys , 75 girls ; BMI ≥ 98th centile relative to United Kingdom 1990 reference data for children aged 5–11 years ) who were r and omly assigned to a best- practice behavioral program ( intervention ) or st and ard care ( control ) . The intervention used family-centered counseling and behavioral strategies to modify diet , physical activity , and sedentary behavior . BMI z score , weight , objective ly measured physical activity and sedentary behavior , fat distribution , quality of life , and height z score were recorded at baseline and at 6 and 12 months . RESULTS . The intervention had no significant effect relative to st and ard care on BMI z score from baseline to 6 months and 12 months . BMI z score decreased significantly in both groups from baseline to 6 and 12 months . For those who complied with treatment , there was a significantly smaller weight increase in those in the intervention group compared with control subjects from baseline to 6 months . There were significant between-group differences in favor of the intervention for changes in total physical activity , percentage of time spent in sedentary behavior , and light-intensity physical activity . CONCLUSIONS . A generalizable , best- practice individualized behavioral intervention had modest benefits on objective ly measured physical activity and sedentary behavior but no significant effect on BMI z score compared with st and ard care among overweight children . The modest magnitude of the benefits observed perhaps argues for a longer-term and more intense intervention , although such treatments may not be realistic for many health care systems OBJECTIVE : To determine whether a 2-year family-based intervention using frequent contact and limited expert involvement was effective in reducing excessive weight compared with usual care . METHODS : Two hundred and six overweight and obese ( BMI ≥85th percentile ) children aged 4 to 8 years were r and omized to usual care ( UC ) or tailored package ( TP ) sessions at university research rooms . UC families received personalized feedback and generalized advice regarding healthy lifestyles at baseline and 6 months . TP families attended a single multidisciplinary session to develop specific goals suitable for each family , then met with a mentor each month for 12 months , and every third month for another 12 months to discuss progress and provide support . Outcome measurements ( anthropometry , question naires , dietary intake , accelerometry ) were obtained at 0 , 12 , and 24 months . RESULTS : BMI at 24 months was significantly lower in TP compared with UC children ( difference , 95 % confidence interval : –0.34 , –0.65 to –0.02 ) , as was BMI z score ( –0.12 , –0.20 to –0.04 ) and waist circumference ( –1.5 , –2.5 to –0.5 cm ) . TP children consumed more fruit and vegetables ( P = .038 ) and fewer noncore foods ( P = .020 ) than UC children , and fewer noncore foods were available in the home ( P = .002 ) . TP children were also more physically active ( P = .035 ) . No differences in parental feeding practice s , parenting , quality of life , child sleep , or behavior were observed . CONCLUSIONS : Frequent , low-dose support was effective for reducing excessive weight in predominantly mild to moderately overweight children over a 2-year period . Such initiatives could feasibly be incorporated into primary care Background : The WATCH IT programme was developed to address the needs of obese children from disadvantaged communities in Leeds and has been running since January 2004 . Results of the pilot phase , prior to a r and omised controlled trial , are presented . Methods : A process evaluation to assess success of implementation was conducted in December 2004 . User views ( parent and child ) were obtained by semi-structured interviews and focus groups . Change in BMI SD score was calculated for children attending between January 2004 and November 2005 . Results : A total of 94 children ( 49 girls , 45 boys ) , mean age ( SD ) 12.2 ( 2.0 ) years attended . They were moderately to severely obese ( mean BMI SDS 3.09 ( 0.45 ) , with low quality of life and self-image scores . There was a significant reduction in overweight at 6 months ( Δ BMI SD −0.07 ) , especially for teenagers ( Δ BMI SD −0.13 ) and girls ( Δ BMI SD −0.07 ) . The programme was successfully implemented . By December 2004 mean attendance was 2.1 ( 0.7 ) clinics per month , and sports sessions 3.3 ( 1.7 ) sessions per month . Fourteen children dropped out and non-attendance was low ( only 7.5 % sessions missed in 12 months ) . Qualitative research indicated significant appreciation of the service , with reported increase in self-confidence and friendships , and reduction in self-harm . Conclusion : WATCH IT offers a model for a community based service for obese children . The programme suggests that effective care can be delivered by health trainers supervised by health professionals , and so potentially provides a cost effective programme within children ’s communities . These findings are encouraging , and need to be substantiated by extension to other locations and evaluation by r and omised controlled trial OBJECTIVE There is a great need for solution-oriented studies and descriptions of interventions for pediatric obesity in real-world setting s. This report describes a group-based behavioral parent-only intervention to promote healthier lifestyle habits and reduce weight status in an obese 12-year-old female participant . METHOD The behavioral parent-only intervention program described was part of a r and omized controlled trial that evaluated the impact of 2 behavioral interventions that addressed dietary intake , physical activity , and weight status in overweight and obese youth living in rural setting s. Both the child and parent were targeted for behavior change . The intervention included 12 group sessions over 4 months . Behavioral strategies , including self-monitoring , goal setting , performance feedback , reinforcement , stimulus control , and instruction in behavioral parenting strategies were flexibly applied to meet the needs of the family . Assessment s were completed at baseline , month-4 posttreatment , and month-10 follow-up . RESULTS The parent attended 10 of 12 treatment sessions . At follow-up the child had lost 17 pounds and grew 1.7 in . in height . The child also experienced improved quality of dietary intake and a drop in the number of self-reported unhealthy weight control behaviors . The parent experienced no notable decrease or increase in BMI . CONCLUSIONS The report describes the successful application of a behavioral intervention to address pediatric obesity that uses a parent-only approach . It is hoped that this presentation will facilitate discussion and help encourage further presentations of how the flexible application of evidence d-based interventions can be applied in real-world setting To decrease BMI in overweight and obese children , improved dietary intake and increased physical activity are key elements . Our objective was to evaluate the impact of a 1-y food and physical activity intervention on energy and macronutrient intake in overweight and obese children . A r and omized open trial was conducted with 92 overweight or obese 10.4 ± 1.08-y-old children . The intervention included 14 group sessions with different themes regarding food and physical activity . Dietary intake was assessed with diet history interviews covering 14 d at baseline and 4-d food records after 1 y and was evaluated according to national dietary recommendations . The control group participated in the same measurements as the intervention group but did not take part in group sessions . After 1 y , both groups had decreased their energy intake ( EI ) relative to total energy expenditure , but the effect was more pronounced for the intervention group than for the control group . At 1 y follow-up , a larger proportion of children in the intervention group compared with the control group met the recommended intake of refined sugar ( P = 0.019 ) . However , the groups did not differ in the proportion children who met the recommended intake of dietary fiber . Further , SFA intake relative to total EI did not differ between the groups at 1 y follow-up . In conclusion , despite a rather comprehensive intervention , only modest effects were achieved with respect to reduced EI and improved macronutrient intake Background / Objectives : To determine if a multi-component family focused education package is more effective than a waiting list control group in treating overweight and obese children . Subjects/ Methods : A 2-year r and omised controlled trial ; 65 overweight and obese children aged 6–14 years were allocated to active intervention in either the first or second year , with body composition monitoring alone in the control period . Anthropometric measurements were undertaken at six monthly intervals and a 7-day food and activity diary were issued . Results : Over the 2 years of the study body mass index ( BMI ) SDS ( z score ) fell significantly in the intervention/control ( I/C ) group , but not in the control/intervention ( C/I ) group . The difference between groups was 0.3 , which was borderline significant ( 95 % confidence interval ( 95 % CI ) −0.62 to 0.02 , P=0.06 ) before adjusting for potential confounding factors . Thirty-three percent of the I/C group and 12 % of the C/I group achieved the target reduction of 0.5 BMI SDS . The I/C group had a significantly greater reduction in the percentage with a BMI above the 99.6th centile at 24 months ( P=0.04 ) and gained 5.7 kg less over the time of the study . There were no significant differences between groups for mean percentage attendance at physical activity sessions ( I/C group=24.1 % , 95 % CI , 15.4–32.9 ; C/I group=31.7 % , 95 % CI , 22.4–41.1 , P=0.229 ) . Conclusions : Children given active intervention followed by body composition monitoring alone reduced their BMI SDS , and fewer children were classified as grossly overweight by the end of the study . If these findings are true , there are important implication s for the provision of services managing overweight in the community Background This study evaluates the effects of an intervention performed by youth health care professionals on child health behaviors . The intervention consisted of offering healthy lifestyle counseling to parents of overweight ( not obese ) 5-year-old children . Effects of the intervention on the child having breakfast , drinking sweet beverages , watching television and playing outside were evaluated . Methods Data were collected with the ' Be active , eat right ’ study , a cluster r and omized controlled trial among nine youth health care centers in the Netherl and s. Parents of overweight children received lifestyle counseling according to the intervention protocol in the intervention condition ( n = 349 ) and usual care in the control condition ( n = 288 ) . Parents completed question naires regarding demographic characteristics , health behaviors and the home environment at baseline and at 2-year follow-up . Cluster adjusted regression models were applied ; interaction terms were explored . Results The population for analysis consisted of 38.1 % boys ; mean age 5.8 [ sd 0.4 ] years ; mean BMI SDS 1.9 [ sd 0.4 ] . There were no significant differences in the number of minutes of outside play or television viewing a day between children in the intervention and the control condition . Also , the odds ratio for having breakfast daily or drinking two or less glasses of sweet beverages a day showed no significant differences between the two conditions . Additional analyses showed that the odds ratio for drinking less than two glasses of sweet beverages at follow-up compared with baseline was significantly higher for children in both the intervention ( p < 0.001 ) and the control condition ( p = 0.029 ) . Conclusions Comparison of the children in the two conditions showed that the intervention does not contribute to a change in health behaviors . Further studies are needed to investigate opportunities to adjust the intervention protocol , such as integration of elements in the regular well-child visit . The intervention protocol for youth health care may become part of a broader approach to tackle childhood overweight and obesity . Trial registration Current Controlled Trials IS RCT BACKGROUND Comparative effectiveness research ( CER ) evidence on childhood obesity provides the basis for effective screening and management strategies in pediatric primary care . The uses of health information technology including decision support tools in the electronic health records ( EHRs ) , as well as remote and mobile support to families , offer the potential to accelerate the adoption of childhood obesity CER evidence . METHODS / DESIGN The Study of Technology to Accelerate Research ( STAR ) is a three-arm , cluster-r and omized controlled trial being conducted in 14 pediatric offices in Massachusetts design ed to enroll 800 , 6 to 12 year old children with a body mass index ( BMI ) ≥ 95th percentile seen in primary care at those practice s. We will examine the extent to which computerized decision support tools in the EHR delivered to primary care providers at the point of care , with or without direct-to-parent support and coaching , will increase adoption of CER evidence for management of obese children . Direct-to-parent intervention components include telephone coaching and twice-weekly text messages . Point-of-care outcomes include obesity diagnosis , nutrition and physical activity counseling , and referral to weight management . One-year child-level outcomes include changes in BMI and improvements in diet , physical activity , screen time , and sleep behaviors , as well as cost and cost-effectiveness . CONCLUSIONS STAR will determine the extent to which decision support tools in EHRs with or without direct-to-parent support will increase adoption of evidence -based obesity management strategies in pediatric practice and improve childhood obesity-related outcomes Objective : The aim of the study was to compare the efficacy of group treatment stressing a health-promoting lifestyle with routine counseling in the treatment of childhood obesity . Design and subjects : Output:	Three important mechanisms were present in all the most effective interventions but absent in all the least effective : 1/ showing families how to change : a ) providing child physical activity sessions , b ) delivering practical behaviour change strategy sessions , c ) providing calorie intake advice ; 2/ ensuring all the family are on board : a ) delivering discussion /education sessions for both children and parents , b ) delivering child-friendly sessions , c ) aim ing to change behaviours across the whole family ; 3/ enabling social support for both parents and children by delivering both child group sessions and parent group sessions . To conclude , programmes should ensure the whole family is on board the programme , that parents and children can receive social support and are not just told what to change , but shown how
MS2757	*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 : Postoperative care for ankle fractures is generally 1 of 2 regimens : 1 ) functional treatment combined with early weightbearing ( EWB ) , or 2 ) immobilization in a cast/orthosis for 6 weeks without weightbearing ( 6WC ) . The objective of this study was 2-fold : 1 ) to follow a prospect i ve group treated with EWB as to long-term subjective and objective outcomes , and 2 ) to compare a subset of this group with a matched group of historic controls treated with 6WC . Design : Prospect i ve , clinical , cohort observation , and retrospective matched pair analysis . Setting : University hospital , level 1 trauma center . Patients : Forty-three patients ( 20 males ; mean age , 49 ± 14 years ) with operated Weber B/C fractures underwent EWB . For comparison , 23 patients of this group were matched to a same number of historic controls with respect to age , gender , body mass index , and fracture type . Intervention : Open reduction and internal fixation ( ORIF ) using a 1/3-tubular-fibula-plate for the fibula , and malleolar screws for the medial malleolus fracture ( in cases with a bimalleolar ankle fracture ) followed by EWB or 6WC . Main Outcome Measurements : Olerud and Tegner scores at follow-up ( at least 12 months after surgery ) , time to full weightbearing , return to work , pain intensity ( numerical rating scale ( NRS ) ) , and hospital stay . Statistical comparisons were performed by using the Mann-Whitney U test or Fisher exact test ( P < 0.05 ) . Results : Patients with EWB were full weightbearing at 7 ± 3 weeks and returned to work at 8 ± 5 weeks after surgery . At follow-up ( mean , 20 ± 11 months after surgery ) , all EWB patients showed good results in the Olerud score ( 90 ± 13 points ) . Matched-pair analysis in 23 patients in each group revealed differences between EWB and 6WC groups for hospital stay ( mean , 10.8 ± 4.7 vs. 13.6 ± 6 days ; P = 0.12 ) , time to full weightbearing ( mean , 7.7 ± 3.1 vs. 13.5 ± 9.4 weeks ; P = 0.01 ) , and time until return to work ( mean 9.2 ± 5.5 vs. 10.8 ± 7 weeks ; P = 0.63 ) . No differences concerning pain intensities were observed ( EWB vs. 6WC : NRS = 1.9 vs. 1.7 ; P = 0.12 ) . At follow-up , Olerud scores were generally considered good for both groups ; however , mean values in EWB patients were slightly higher ( 87 ± 14 vs. 79 ± 19 points ; P = 0.25 ) . In both groups , the majority of patients reached their preinjury level of activity as demonstrated by Tegner scores . Conclusions : EWB patients tolerated earlier full weightbearing compared with 6WC patients , and there were no disadvantages with EWB compared with 6WC concerning hospital stay , pain intensities , time until return to work , and Olerud/Tegner Scores . Potential c and i date s for EWB are patients with a stable osteo synthesis of their fractured ankles as judged by the responsible surgeon , compliance , and high motivation STUDY DESIGN Prospect i ve inception cohort study of 62 consecutive patients seen in 2 orthopaedic clinics following ankle fracture . OBJECTIVES To investigate 4 putative predictors ( age , fracture classification , acute management [ surgical or nonsurgical ] , and ankle dorsiflexion range of motion measured at the time of cast removal ) of outcome after ankle fracture and to develop simple predictive models of outcome after ankle fracture . BACKGROUND Ankle fracture is a common condition . However , few studies have investigated factors that predict outcome after ankle fracture . METHODS AND MEASURES Sixty-two consecutive subjects aged 17 or older with ankle fractures were recruited from 2 hospital orthopaedic clinics . Outcome measures recorded at 6 weeks and 6 months after cast removal included 2 functional question naires , patients ' ratings of global improvement , and a measure of ankle dorsiflexion . The predictive value of 4 variables selected a priori was analyzed using bivariate and stepwise multiple linear regression . RESULTS Ankle dorsiflexion and fracture classification predicted outcome 6 weeks and 6 months after cast removal for all outcome measures used ( P < .05 , r2 = 0.09 - 0.47 ) . Fracture management ( surgical or nonsurgical ) inconsistently predicted outcome at both 6 weeks and 6 months , and age did not predict outcome at either 6 weeks or 6 months after cast removal . The predictive models explain between 19 % and 58 % of the variance in outcomes 6 weeks after cast removal and 19 % to 52 % of the variance in outcomes 6 months after cast removal . CONCLUSION Ankle dorsiflexion measured at the time of cast removal and fracture classification are clinical ly significant predictors of outcome after ankle fracture ; however , much unexplained variation in outcomes still exists 40 patients with dislocated bimalleolar and trimalleolar ankle fractures took part in this r and omized study . All ankles were operated on using cerclage , staples and pins . Active ankle movement with weight bearing in an orthosis was compared with active ankle movement without weight bearing using a dorsal splint . Stereophotogrammetric analysis showed small movements in the ankle mortise in both groups but conventional radiography revealed no fracture redislocation . The clinical results did not differ . This study was design ed as the second part of a consecutive project . In the first part , early and late weight bearing in a cast without ankle movements was compared ( Ahl et al. 1987b ) . In comparing the first and the second parts of the study , a small but significant increase in fracture instability was observed in the early motion group . No lasting superior clinical result was achieved by early ankle movement . After operation on dislocated bimalleolar ankle fractures , early postoperative weight bearing in a walking cast is recommended Background Despite conflicting results after surgically treated ankle fractures few studies have evaluated the effects of different types of training programs performed after plaster removal . The aim of this study was to evaluate the effects of a 12-week st and ardised but individually suited training program ( training group ) versus usual care ( control group ) after plaster removal in adults with surgically treated ankle fractures . Methods In total , 110 men and women , 18 - 64 years of age , with surgically treated ankle fracture were included and r and omised to either a 12-week training program or to a control group . Six and twelve months after the injury the subjects were examined by the same physiotherapist who was blinded to the treatment group . The main outcome measure was the Olerud-Mol and er Ankle Score ( OMAS ) which rates symptoms and subjectively scored function . Secondary outcome measures were : quality of life ( SF-36 ) , timed walking tests , ankle mobility tests , muscle strength tests and radiological status . Results 52 patients were r and omised to the training group and 58 to the control group . Five patients dropped out before the six-month follow-up result ing in 50 patients in the training group and 55 in the control group . Nine patients dropped out between the six- and twelve-month follow-up result ing in 48 patients in both groups . When analysing the results in a mixed model analysis on repeated measures including interaction between age-group and treatment effect the training group demonstrated significantly improved results compared to the control group in subjects younger than 40 years of age regarding OMAS ( p = 0.028 ) , muscle strength in the plantar flexors ( p = 0.029 ) and dorsiflexors ( p = 0.030 ) . Conclusion The results of this study suggest that when adjusting for interaction between age-group and treatment effect the training model employed in this study was superior to usual care in patients under the age of 40 . However , as only three out of nine outcome measures showed a difference , the beneficial effect from an additional st and ardised individually suited training program can be expected to be limited . There is need for further studies to eluci date how a training program should be design ed to increase and optimise function in patients middle-aged or older . Trial Registration Current Controlled Trials OBJECTIVE The primary aim of this study was to determine the effectiveness and cost-effectiveness of adding manual therapy to a physiotherapy programme for ankle fracture . DESIGN Assessor-blinded r and omized controlled trial . PARTICIPANTS Ninety-four adults were recruited within one week of cast removal for isolated ankle fracture . Inclusion criteria were : they were able to weight-bear as tolerated or partial weight-bear , were referred for physiotherapy , and experienced pain . Ninety-one participants completed the study . METHODS Participants were r and omly allocated to receive manual therapy ( anterior-posterior joint mobilization over the talus ) plus a st and ard physiotherapy programme ( experimental ) , or the st and ard physiotherapy programme only ( control ) . They were assessed by a blinded assessor at baseline , and at 4 , 12 and 24 weeks . The main outcomes were activity limitation and quality of life . Information on costs and healthcare utilization was collected every 4 weeks up to 24 weeks . RESULTS There were no clinical ly worthwhile differences in activity limitation or quality of life between groups at any time-point . There was also no between-group difference in quality -adjusted life-years , but the experimental group incurred higher out-of-pocket costs ( mean between-group difference = AU$200 , 95 % confidence interval 26 - 432 ) . CONCLUSION When provided in addition to a physiotherapy programme , manual therapy did not enhance outcome in adults after ankle fracture In a prospect i ve , r and omized study , 30 patients were evaluated after ankle fracture treated by means of open reduction and internal fixation . The patients were r and omized to either postoperative immobilization in a plaster cast for 6 weeks or early mobilization ( 1–2 weeks after surgery ) in an ankle brace . Both regimens allowed weightbearing . Evaluation after 10 weeks and after 12 months included clinical assessment and isokinetic muscle strength measurements . Patients with impaired ankle function , as shown by means of an ankle score at 12 months , were followed for 3 years . At 10 weeks , impaired muscle torque and restricted range of motion was found on the affected side . This impairment was significantly less in the brace group . At 12 months , range of motion of the ankle and subtalar joints was restored , but dorsiflexion was still better in the brace group . Score values from a functional score did not correlate with muscle strength In a monocenter r and omized controlled trial , 45 patients with isolated malleolar fracture type OTA/AO 44 A1–B2 undergoing ORIF were allocated r and omly to a postoperative treatment either with a vacuum-stabilized orthesis with prescribed full weight bearing after the second week ( 23 patients ) ( orthesis group — OG ) or with functional aftertreatment with partial weight bearing of 15 kg for 6 weeks ( 22 patients ) ( control group — CG ) . Outcomes were compared at 6- and 10-week follow-up examinations . The Olerud and Mol and er ankle ( OMA ) score , ankle swelling , usage of crutches , range of motion , Short Form 12 , patient-reported visual analogue scales ( VAS ) ( pain , comfort , walking confidence ) and time to return to work were evaluated . All patients of OG showed reduced swelling at discharge . The median OMA scores after 6 weeks were 42 and 42.5 ( p = 0.46 ) and after 10 weeks 69 and 72 ( p = 0.55 ) in the OG and CG , respectively . The time to achieve secure walking capacity was reduced by 1 day ( p = 0.03 ) in the OG . After ORIF of simple malleolar fractures , patients with a vacuum-stabilized orthesis can bear full weight 2 weeks postoperatively . This group experienced no adverse events . Postoperative swelling was significantly reduced and of the ability to walk on stairs confidently was shorter as compared to a functional aftertreatment without any external stabilization of the ankle In the prospect i ve cohort study reported here , we used the Short Musculoskeletal Function Assessment ( SMFA ) question naire to assess rate of return of functional outcome after open reduction and internal fixation of unstable ankle fractures ( Orthopaedic Trauma Association/Arbeitsgemeinschaft für Osteosynthesefragen [ OTA/AO ] 44B and 44C ) at a level II trauma center over the course of 1 year . The entire group of 69 consecutive adults improved significantly ( P<.01 ) on the SMFA Emotional Status and Dysfunction scales from 2 to 4 months and on the Mobility and Daily Activities scales from 2 to 4 months and from 4 to 6 months . There were no significant changes on the Arm/H and Function and Bother scales . There was a significant effect of age on Mobility , Daily Activities , and Dysfunction , with older patients ( > or = 50 years ) obtaining higher ( worse ) scores . There was no significant effect on patient sex on any of the scales . Patients with 44C fractures ( vs 44B fractures ) had significantly ( P = .05 ) higher mean Bother scores at 6 months . There were no significant differences arising from presence or absence of a fracture of the medial malleolus . Our SMFA data show that older Output:	Studies with older participants and predominantly male participants tended to report worse functional outcomes .
MS2758	*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 Venous thromboembolism is known to be an important social and health care problem because of its high incidence among patients who undergo surgery . Studies on the mechanical prophylaxis of thromboembolism after gynaecological pelvic surgery are few . The aim of our study was to evaluate the effect of mechanical thromboembolism prophylaxis after gynaecological pelvic surgery using a combination of graduated compression stockings ( GCS ) and intermittent pneumatic compression ( IPC ) or GCS alone . METHODS The study was performed on 108 patients who were r and omly assigned to two groups . The first group received GCS before the operation and IPC during the operation ( IPC + GCS group ) . The second group received GCS before the operation ( GCS group ) . To analyze the effect of the preventive measures and the laboratory examination on the incidence of thrombosis and to compare the safety of these measures , the incidence of adverse reactions was assessed . RESULTS The morbidity associated with DVT was 4.8 % ( 5/104 ) in the IPC + GCS group and 12.5 % ( 14/112 ) in the GCS group . There were significant statistical differences between the two groups . There were no adverse effects in either group . CONCLUSIONS The therapeutic combination of GCS and IPC was more effective than GCS alone for thrombosis prevention in high-risk patients undergoing gynaecological pelvic surgery , and there were no adverse effects in either group We studied 80 patients who were older than 50 years of age to determine if grade d elastic compression stockings reduced the frequency of postoperative thrombosis in patients undergoing dextran 70 prophylaxis . All of the patients received a total of 2,000 mL of dextran 70 during three days ; according to a r and om table , each of the patients had one leg encased in a grade d compression stocking for one week . Thrombosis development was screened with the fibrinogen I 125 test . Eight patients manifested thrombosis-one in the thigh and seven in the calf -- localized to the unstockinged leg , a frequency significantly greater than the zero frequency in the stockinged leg . No untoward effects of this combination prophylaxis were noted INTRODUCTION Darexaban ( YM150 ) is an oral direct factor Xa inhibitor in clinical development for prophylaxis of venous thromboembolism ( VTE ) after major orthopaedic surgery . The objective of this study was to assess the efficacy and safety of darexaban 15 mg twice daily ( bid ) in Japanese patients undergoing major abdominal surgery . MATERIAL S AND METHODS In a Phase III , multicentre , r and omized , open-label , mechanical prophylaxis-controlled , parallel-group study , adult patients ( aged ≥ 40 years ) were r and omized to darexaban 15 mg bid or mechanical prophylaxis , for 28 days . The primary efficacy outcome was incidence of total VTE at Day 12 . Adverse events ( AEs ) and bleeding events were recorded throughout the study . RESULTS The total VTE incidence at Day 12 was 2.6 % in the darexaban 15 mg bid group ( 95 % confidence interval [ CI ] : 0.32 , 9.07 ) , compared with 15.0 % ( 95 % CI : 5.71 , 29.84 ) in the mechanical prophylaxis group . During the investigational period , the incidence of all bleeding events was 9.5 % in the darexaban 15 mg bid group and 3.9 % in the mechanical prophylaxis group . In the darexaban 15 mg bid group , one patient experienced major bleeding and five patients experienced clinical ly relevant non-major ( CRNM ) bleeding . No patients in the mechanical prophylaxis group experienced major and /or CRNM bleeding . AEs were reported in 71.4 % of patients in the darexaban 15 mg bid group and 76.5 % of patients in the mechanical prophylaxis group ; the most frequent AEs across both treatment groups were constipation and insomnia . No patients died during the study . CONCLUSIONS Based on these findings , darexaban is expected to be effective for the prevention of VTE in patients undergoing major abdominal surgery . ( CLINICAL TRIAL REGISTRATION NUMBER NCT00942435 ) A study of 95 patients determined the incidence of postoperative venous thrombosis and the effectiveness of simple prophylactic measures . In addition , the accuracy of the radioactive fibrinogen technique for the detection of thrombosis was compared to venography . Deep venous thrombosis was detected in six of 44 ( 14 % ) control patients . However , only two of 51 ( 4 % ) patients on whom prophylactic measures were applied developed thrombosis . The ages of the patients with thrombosis occurring postoperatively were significantly higher than the ages of the other patients in this study . There was an excellent correlation of the results obtained by the radioactive method with those of venography . Laboratory tests indicated a deficient endogenous fibrinolytic activity in those patients who developed thrombosis The effect of incremental increases in external pressure , applied to the leg , on blood volume flow in the femoral vein was studied in dogs . Clinical investigation of external pressure increases was also carried out on nine patients undergoing surgery for varicose veins . An external pressure between 5 and 15 mm . Hg caused a sustained increase in mean femoral vein flow both in a control and in the compressed limb . Above 15 mm . Hg external pressure flow decreased in the compressed limb but was maintained at an increased level in the control limb . If external compression is to be used to prevent and treat deep vein thrombosis its application must be carefully controlled Lower‐limb venous haemodynamics were studied prospect ively in 40 patients ( 24 women , 16 men of median age 52 years ) undergoing laparoscopic cholecystectomy . Patients were r and omized to wear compression stockings during surgery or no stockings . All received subcutaneous heparin prophylaxis . Venous capacitance and outflow were measured non‐invasively before , during and after pneumo‐peritoneum . In the group without compression stockings ( 20 patients ) venous capacitance and outflow decreased during pneumoperitoneum in most patients . In the group wearing stockings ( 20 patients ) the changes were less pronounced or abolished . There was a significant difference between the groups in venous capacitance and outflow ratios at mid‐operation : median ( interquartile range ) 0‐89 ( 0‐56‐1‐16 ) and 0‐89 ( 0‐56‐1‐15 ) respectively in the group without stockings versus 1‐48 ( 1‐09‐2‐19 ) and 1‐71 ( 1‐20‐2‐19 ) respectively in that with stockings ( P < 0.001 ) . Pneumoperitoneum creates a significant resistance to venous return . Compression stockings counteract the changes observed In a prospect i ve , r and omized study on 114 patients undergoing major abdominal surgery , the prophylactic effect of dihydroergotamine ( DHE ) combined with low-dose heparin ( LDH ) against postoperative deep vein thrombosis ( DVT ) was compared with that of peroperative intermittent pneumatic calf compression ( IPCC ) . The additive effect of graduated pressure stockings was also studied , by r and omizing a stocking to the right or left leg in each patient . The 125I-fibrinogen test was used to diagnose DVT . The incidence of postoperative DVT was significantly lower in the DHE-LDH than in the IPCC group ( 4 % v. 19 % ) . In the IPCC group the incidence of postoperative DVT was equal in legs with and without stocking . The study thus indicated that DHE-LDH is more effective than peroperative IPCC in preventing DVT after major abdominal surgery , and that graduated pressure stockings do not enhance the prophylactic effect of peroperative IPCC Purpose Venous thromboembolism ( VTE ) is a frequent and serious problem in intensive care units ( ICU ) . Anticoagulant treatments have demonstrated their efficacy in preventing VTE . However , when the bleeding risk is high , they are contraindicated , and mechanical devices are recommended . To date , mechanical prophylaxis has not been rigorously evaluated in any trials in ICU patients . Methods In this multicenter , open-label , r and omized trial with blinded evaluation of endpoints , we r and omly assigned 407 patients with a high risk of bleeding to receive intermittent pneumatic compression ( IPC ) associated with graduated compression stockings ( GCS ) or GCS alone for 6 days during their ICU stay . The primary endpoint was the occurrence of a VTE between days 1 and 6 , including nonfatal symptomatic documented VTE , or death due to a pulmonary embolism , or asymptomatic deep vein thrombosis detected by ultrasonography systematic ally performed on day 6 . Results The primary outcome was assessed in 363 patients ( 89.2 % ) . By day 6 , the incidence of the primary outcome was 5.6 % ( 10 of 179 patients ) in the IPC + GCS group and 9.2 % ( 17 of 184 patients ) in the GCS group ( relative risk 0.60 ; 95 % confidence interval 0.28–1.28 ; p = 0.19 ) . Tolerance of IPC was poor in only 12 patients ( 6.0 % ) . No intergroup difference in mortality rate was observed . Conclusions With the limitation of a low statistical power , our results do not support the superiority of the combination of IPC + GCS compared to GCS alone to prevent VTE in ICU patients at high risk of bleeding Totally , 150 patients , subjected to total hip arthroplasty , were r and omly allocated into three prophylactic groups with either conventional dextran alone or with additional grade d compression stockings or with additional preoperative administration of dextran . The overall frequency of deep venous thrombosis ( DVT ) , as studied by radioactive fibrinogen uptake test and ascending phlebography of the operated on thigh was in the conventional dextran group 46 percent , the additional stockinged group 30 percent , and in the additional preoperative dextran group 52 percent . In the stockinged group , there was a lower frequency of DVT in the nonoperated on leg as well as , on an average , about 350 mL less peroperative bleeding as compared with the other two groups . No adverse reaction occurred from dextran administration . Increased and prolonged postoperative administration of dextran decrease the number of femoral DVTs Postoperative thromboembolic complications were evaluated in 2578 patients undergoing elective abdominal surgery , all receiving prophylaxis with low molecular weight heparin . A positive fibrinogen uptake test ( FUT ) developed in 217 patients ( 8.4 % ) , while 37 patients ( 1.4 % ) had major thromboembolism ( TE , defined as proximal deep vein thrombosis and /or pulmonary embolism , verified with phlebography , pulmonary scintigraphy or autopsy ) . In only 14 % a positive FUT was associated with a major TE event . In 19 % of the patients with major TE the FUT was negative . In multiple logistic regression the independent predictors for major TE were partially different from those for positive FUT . Thirty day mortality was 3.0 % . There were significant associations between both positive FUT and major TE on one h and and mortality on the other ( relative risks 2.4 and 5.8 , respectively ) . FUT is not a good predictor of major TE . Both positive FUT and major TE indicate a significant risk of postoperative death Seventy-eight patients having elective total hip replacement were r and omised into 3 groups A ) control ; B ) low molecular weight heparin : ( enoxaparin 40 mg once daily ) and C ) enoxaparin ( 40 mg once daily ) plus graduated elastic compression ( TEDR stockings ) for 8 - 12 days . All patients had a preoperative perfusion lung scan and chest X-Ray and a postoperative perfusion/ventilation scan together with bilateral ascending venography on days 8 - 12 . A blood sample was taken preoperatively , on the 1st , 3rd and 5th postoperative day and at the end of the study . The control group received placebo injections . The venograms and V/Q scans were reported blindly by an independent panel of three and one radiologists respectively . An independent panel of assessors stopped entry in the control group when a total of 45 patients were admitted according to Ethics Committee directives . The study continued with groups B and C. The incidence of DVT ( including isolated asymptomatic calf thrombi ) was as follows : Group A ( n = 14 ) 93 % ; Group B ( n = 32 ) 38 % ; Group C ( n = 32 ) 25 % ( chi 2 ; p < 0.001 for group A versus B or C ) . The incidence of proximal DVT was : Group A 57 % ; group B 28 % ; group C 13 % ( chi 2 ; p = 0.057 for group A versus B and p < 0.005 for group A versus C ) . The incidence of silent pulmonary embolism ( PE ) ( new defect on V/Q scan ) was 28 % ( 8 out of 29 ) in patients with and 5 % ( 2 out of 43 ) in patients without DVT ( chi 2 ; p < 0.02 ) . The combination of high TAT and low anti-Xa activity on the 1st postoperative day identified a high risk group of patients who had a 56 % incidence of proximal DVT on the 8th to Output:	AUTHORS ' CONCLUSIONS GCS are effective in diminishing the risk of DVT in hospitalised patients , with strong evidence favouring their use in general and orthopaedic surgery .
MS2759	*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 Recent studies have shown that omentin-1 derived from adipokines can affect physiological regulations and some metabolic dis-eases such as type 2 diabetes mellitus ( T2DM ) . Methods The purpose of this study was to examine the impact of 12 weeks of aerobic ( cycle ergometer ) , resistance , and combined exercises on omentin-1 level , glucose and insulin resistance indices in overweight middle age women with T2DM . In this study , 60 overweight middle age diabetic women were selected using simple r and om sampling and they were assigned to three groups of aerobic exercise ( n=12 ) , resistant exercise ( n=12 ) and combined exercise ( n=13 ) , and one control group ( n=15 ) . Exercises were done in a three times per week sessions for a total of 12 weeks . Blood sample s were collected before each exercise session and 24 hours after of the last session . Results Present study showed that fasting blood sugar decreased significantly in all intervention groups , while homeostasis model assessment of insulin resistance ( HOMA-IR ) decreased only in the aerobic and combined exercises groups . Furthermore , there was a significant increase in the omentin-1 level only in the combined exercise group . Conclusion Compared to aerobic and resistance exercises , 12 weeks of combined exercise was more efficient in improving HOMA-IR and increasing serum omentin-1 among women with T2DM This prospect i ve study aim ed to present the reference range of amniotic fluid glucose ( AFglu ) among second trimester pregnant women in southern Thail and , to evaluate the possibility of predicting subsequent gestational diabetes mellitus ( GDM ) using AFglu , and to estimate AFglu cut-off levels for identifying pregnancies at high or low risk for subsequent GDM in singleton pregnancies undergoing genetic amniocentesis due to advanced maternal age . A total of 438 eligible pregnant women were analysed , among whom 58 were subsequently diagnosed as having GDM . The reference range that included the central 95 % of AFglu values at 16 , 17 and 18 weeks of gestation in women not subsequently developing GDM was determined from a linear regression model . Logistic regression was used to identify predictors of subsequent GDM . Odds ratio of subsequent diagnosed GDM participant increased by 7 % for each 1 mg/dl increase in AFglu . Risk of subsequent GDM was also increased in women aged over 36 years and in 17–18 weeks compared to 16 weeks of gestation . Depending on gestational and maternal age , AFglu levels above 51 to 75 mg/dl were at elevated risk of subsequent GDM ( likelihood ratio 2.38 ) . We conclude that AFglu tended to decrease with increasing of gestational age . Gestational age and maternal age accompanied with elevated AFglu are predictive factors for subsequent GDM OBJECTIVE Omentin is a protein expressed and secreted from visceral but not subcutaneous adipose tissue , which increases insulin sensitivity in human adipocytes . However , its pathophysiologic role in humans remains largely unknown . The objective of this study is to assess plasma omentin-1 levels in patients with type 2 diabetes mellitus ( T2DM ) and matched control subjects and to investigate the effects of liraglutide on plasma omentin-1 levels in patients with T2DM . PATIENTS AND METHODS Thirty T2DM patients with poor glycemic control after more than 3 months of treatment with one or two OHA(s ) ( T2DM ) , and 30 matched normal glycaemic controls ( NGT ) participated in the study . The T2DM group was given an injection of liraglutide once-daily for 16 weeks . Plasma omentin-1 levels were measured by enzyme-linked immunosorbent assay and the relationship between plasma omentin-1 levels and metabolic parameters was also analyzed . RESULTS Plasma omentin-1 levels were lower in T2DM than in the control ( 19.3 ± 4.0 μg/L vs. 26.4 ± 6.0 μg/L , P < 0.01 ) . Plasma omentin-1 levels increased significantly in T2DM patients after treatment with liraglutide compared with pre-treatment ( 19.3 ± 4.0 μg/L vs. 21.2 ± 3 . 9 μg/L , P < 0.01 ) . In all diabetic patients , multiple regression analysis showed that FINS and HOMA-IR were independently associated with plasma omentin-1 levels . CONCLUSIONS In T2DM patients , plasma omentin-1 levels decreased , but significantly increased after the treatment with liraglutide and metformin . These data suggest that liraglutide may play a role in increasing omentin-1 levels in T2DM patients AIMS To assess the effects of two commonly used oral hypoglycemic medications metformin and pioglitazone on serum concentrations of omentin and leptin in patients with newly diagnosed type 2 diabetes . METHODS In a clinical trial setting ( NCT01593371 ) , patients were r and omly allocated to either metformin 1000 mg daily ( n=41 ) , or pioglitazone 30 mg daily ( n=50 ) . Serum concentrations of omentin and leptin were measured at baseline and after 12weeks . Patients ' weight , waist circumference , blood pressure , fasting plasma glucose , fasting insulin , HbA1c , highly sensitive C-reactive protein , and serum lipids were also measured at the two visits . RESULTS Baseline concentrations of omentin and leptin were not different between the two arms of the trial . After three months , metformin decreased both omentin and leptin concentrations in women , and leptin concentrations only in men . On the other h and , pioglitazone reduced both adipokines only in women , but not men . Univariate and multivariate ANCOVA models revealed that both interventions are equally effective in reducing omentin concentration ( p=0.497 for women and 0.344 for men in multivariate models controlling for the effects of confounding variables ) . Similarly , neither medication was more effective in reducing leptin concentrations after three months ( p=0.822 for women and 0.441 for men in multivariate models ) . CONCLUSIONS Metformin and pioglitazone at pharmacologic doses are equally effective in alteration of serum omentin and leptin concentrations in patients with diabetes , albeit sex differences in response to medications exist . Implication of these findings on long term management and complication prevention of diabetes needs to be eluci date BACKGROUND Weight loss is often key in the management of obese or overweight patients with type 2 diabetes , yet few treatments for diabetes achieve clinical ly meaningful weight loss . We aim ed to assess the efficacy , tolerability , and safety of treatment with MEDI0382 , a balanced glucagon-like peptide-1 and glucagon receptor dual agonist developed to provide glycaemic control and weight loss , in patients with type 2 diabetes . METHODS This r and omised , placebo-controlled , double-blind , combined multiple-ascending dose ( MAD ) and phase 2a study was done at 11 study sites ( hospitals and contract research organisations ) in Germany . We enrolled patients aged 18 - 65 years with controlled type 2 diabetes ( glycated haemoglobin A1c [ HbA1c ] levels of 6·5 - 8·5 % at screening ) and a body-mass index between 27 kg/m2 and 40 kg/m2 . An interactive web-response system was used to r and omly assign patients to receive MEDI0382 or placebo . Patients were r and omly assigned 2:1 in cohorts A-C and 3:1 in cohorts D and E in the MAD portion of the study , and 1:1 in the phase 2a portion . R and omisation was done by a contracted third-party operator who was not involved in the clinical operations of the study . The pharmacists , participants , and study site personnel involved in treating and assessing participants were masked to treatment allocation . Patients received once-daily subcutaneous injections of the study drug at doses of no more than 300 μg for 22 days or less in the MAD portion of the study , and a dose of no more than 200 μg for 41 days or less in the phase 2a portion . The two primary endpoints of the phase 2a portion were the change from baseline to day 41 in glucose area under the curve at 0 - 4 h ( AUC0 - 4 h ) after a mixed-meal tolerance test ( MMTT ) , assessed in all participants who received at least one dose of study drug and whose measurements were taken at baseline and day 41 , and change from baseline in bodyweight , assessed in the intention-to-treat ( ITT ) population . Safety analyses were done in all participants who received any study drug analysed according to the treatment they received . This study is registered with Clinical Trials.gov , number NCT02548585 . FINDINGS Patients were recruited between Dec 9 , 2015 , and Feb 24 , 2017 . 61 patients were r and omly assigned to the MAD part of the study ( 42 to MEDI0382 and 19 to placebo ) . 51 patients were r and omly assigned to the phase 2a part , of whom 25 were r and omly assigned to MEDI0382 and 26 to placebo . In the phase 2a study , three patients in the MEDI0382 group and one in the placebo group discontinued , all as a result of adverse events . 22 ( 88 % ) patients in the MEDI0382 group and 25 ( 96 % ) in the placebo group received at least one dose and had measurements taken at baseline and day 41 . Glucose AUC0 - 4 h post MMTT decreased significantly with MEDI0382 versus placebo ( least squares [ LS ] mean -32·78 % [ 90 % CI -36·98 to -28·57 ] vs -10·16 % [ -14·10 to -6·21 ] , and the mean difference was -22·62 % [ -28·40 to -16·85 ] ; p<0·0001 ) . In the ITT population , reduction in bodyweight was significantly greater with MEDI0382 than with placebo ( LS mean -3·84 kg [ 90 % CI -4·55 to -3·12 ] vs -1·70 kg [ -2·40 to -1·01 ] and mean difference of 2·14 kg [ -3·13 to -1·31 ] ; p=0·0008 ) . The proportion of patients who had a treatment-emergent adverse event ( TEAE ) was similar between treatment groups ( 22 [ 88 % ] of 25 in the MEDI0382 group vs 23 [ 88 % ] of 26 in the placebo group ) ; gastrointestinal disorders ( 18 [ 72 % ] vs 13 [ 40 % ] ) and decreased appetite ( five [ 20 % ] vs none ) occurred more frequently with MEDI0382 than placebo . No participants in the MEDI0382 group had a grade 3 or worse TEAE ( vs two [ 8 % ] in the placebo group ) . INTERPRETATION MEDI0382 has the potential to deliver clinical ly meaningful reductions in blood glucose and bodyweight in obese or overweight individuals with type 2 diabetes . FUNDING MedImmune BACKGROUND Glucagon-like peptide 1 receptor agonists differ in chemical structure , duration of action , and in their effects on clinical outcomes . The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown . We aim ed to determine the safety and efficacy of albiglutide in preventing cardiovascular death , myocardial infa rct ion , or stroke . METHODS We did a double-blind , r and omised , placebo-controlled trial in 610 sites across 28 countries . We r and omly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease ( at a 1:1 ratio ) to groups that either received a subcutaneous injection of albiglutide ( 30 - 50 mg , based on glycaemic response and tolerability ) or of a matched volume of placebo once a week , in addition to their st and ard care . Investigators used an interactive voice or web response system to obtain treatment assignment , and patients and all study investigators were masked to their treatment allocation . We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death , myocardial infa rct ion , or stroke , which was assessed in the intention-to-treat population . If non-inferiority was confirmed by an upper limit of the 95 % CI for a hazard ratio of less than 1·30 , closed testing for superiority was prespecified . This study is registered with Clinical Trials.gov , number NCT02465515 . FINDINGS Patients were screened between July 1 , 2015 , and Nov 24 , 2016 . 10 793 patients were screened and 9463 participants were enrolled and r and omly assigned to groups : 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo . On Nov 8 , 2017 , it was determined that 611 primary endpoints and a median follow-up of at Output:	Decreased omentin-1 concentrations may be an important indicator for gestational diabetes mellitus and type 2 diabetes mellitus .
MS2760	*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 this study is to evaluate the outcome of an innovative , minimally invasive sling technique with autologous tissue in women with concomitant incontinence and anterior vaginal wall prolapse ( AVWP ) . Material s and Methods : Fifty-six women with stress urinary incontinence ( SUI ) or mixed urinary incontinence and AVWP were r and omly assigned into two groups : In Group A ( 26 patients ) , anterior colporrhaphy ( Kelly placation ) and sling placement using a strip of anterior vaginal wall were performed , and in Group B ( 30 patients ) , transvaginal mesh correction of AVWP and tension-free vaginal tape ( TVT ) insertion ( retropubic – craniocaudal route ) using polypropylene mesh were carried out . The patients were followed-up for over 18 months and were assessed objective ly using a 48 h frequency-volume chart , a 48 h pad test and a st and ardized stress test . Related surgical complications and outcomes were recorded and compared . Results : Surgical cure rates for Group A and Group B at the first ( 3 days ) and last ( 18 months ) post-operative visits were 62 % and 84 % ; and 54 % , and 72 % , respectively ( P = 0.09 and 0.31 ) . Complications occurred in 9 patients ( 44 % ) of Group B , but only 3 patients ( 12 % ) in Group A. Conclusion : Vaginal sling surgery using an anterior vaginal wall strip can improve SUI and in comparison with propylene mesh is associated with lower complication rates . Although , the surgical success rate of this technique is lower than T-Sling , larger studies with selected patients will help assess the suitable patients for this pelvic reconstructive surgery OBJECTIVE : To compare anatomical and patient-reported outcomes at 12 months postoperatively for women who had anterior compartment pelvic organ prolapse ( POP ) surgery using a repair augmented with porcine small intestine submucosa mesh ( Mesh Group ) compared with those who had a native tissue repair ( No Mesh Group ) . METHODS : This was a r and omized controlled trial with 12 months follow-up . The surgical procedure was identical in both groups except for the placement of intervening mesh . The primary outcome was anatomical “ cure ” ( Ba of −1 or less on Pelvic Organ Prolapse Quantification [ POP-Q ] ) . Secondary outcomes included POP-Q stage , patient-reported outcomes , and patient satisfaction . The study was powered to detect a 40 % difference at 80 % power ( & agr;=0.05 ) . RESULTS : Fifty-seven women were r and omized ( 28 to Mesh Group , 29 to No Mesh Group ) . Forty-five ( 79 % ) underwent concomitant surgery . At the 12-month follow-up , 56 % ( 15/27 ) in the Mesh Group and 61 % ( 17/28 ) in the No Mesh Group were considered cured ( relative risk 0.90 , 95 % confidence interval 0.52–1.54 ) . There were no significant differences between groups in recurrent or persistent prolapse ( 7 % in each group ) nor in patient-reported outcomes at 12 months . Pelvic girdle pain occurred in 4 of 27 in the Mesh Group and 3 of 28 in the No Mesh Group . CONCLUSION : No significant differences were observed in anatomical or patient-reported outcomes outcome parameters at 12 months after correction of symptomatic anterior POP by mesh or no mesh repair . In our study , porcine small intestine submucosa mesh did not confer additional benefit over a native tissue repair . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT0095544 . LEVEL OF EVEDIENCE : Introduction and hypothesisTo compare the efficacy of a collagen-coated polypropylene mesh and anterior colporrhaphy in the treatment of stage 2 or more anterior vaginal wall prolapse . Methods Prospect i ve , r and omized , multicenter study conducted between April 2005 and December 2009 . The principal endpoint was the recurrence rate of stage 2 or more anterior vaginal wall prolapse 12 months after surgery . Secondary endpoints consisted of functional results and mesh-related morbidity . Results One hundred and forty-seven patients were included , r and omized and analyzed : 72 in the anterior colporrhaphy group and 75 in the mesh group . The anatomical success rate was significantly higher in the mesh group ( 89 % ) than in the colporrhaphy group ( 64 % ) ( p = 0.0006 ) . Anatomical and functional recurrence was also less frequent in the mesh group ( 31.3 % vs 52.2 % , p = 0.007 ) . Two patients ( 2.8 % ) were reoperated on in the colporrhaphy group for anterior vaginal wall prolapse recurrence . No significant difference was noted regarding minor complications . An erosion rate of 9.5 % was noted . De novo dyspareunia occurred in 1/14 patients in the colporrhaphy group and in 3/13 patients in the mesh group . An analysis of the quality of life question naires showed an overall improvement in both groups , with no statistical difference between them . Satisfaction rates were high in both groups ( 92 % in the colporrhaphy group and 96 % in the mesh group ) . Conclusion Trans-obturator Ugytex ® mesh used to treat anterior vaginal wall prolapse gives better 1-year anatomical results than traditional anterior colporrhaphy , but with small a increase in morbidity in the mesh group Introduction and hypothesisThis trial aim ed to compare the outcomes of native vaginal tissue repair versus polypropylene mesh repair for the treatment of severe genital prolapse . Methods This multicenter r and omized trial included 184 women , with POP-Q stage 3 or 4 . They were r and omly assigned to undergo surgical treatment using native tissue repair ( n = 90 ) or synthetic mesh repair ( n = 94 ) . Native tissue repair surgery was performed according to site-specific defects , including sacrospinous ligament fixation for apical defects . Mesh repair ( Prolift ™ ) was performed in accordance with manufacturer recommendations . Hysterectomy was performed in all cases of uterine prolapse . Statistical tests were used to compare between-group and within-group differences before the surgery and at 1-year follow-up . We considered cure to have occurred when the POP-Q point evaluation was equal to or less than 0 and POP-Q point C better than or equal to half the total vaginal length ( TVL ) after 1 year . The patients answered the Prolapse Quality -of-Life Question naire ( PQoL ) and the Sexual Quotient Female Version ( QS-F ) question naire . Results Both groups were homogeneous preoperatively . There were no differences between the groups in operative time , complications or pain . At 1-year follow-up , anatomical cure rates were better in the mesh group in the anterior compartment ( p = 0.019 ) . Significant improvement in PQoL scores at 1-year follow up were observed in each group ; between-group comparisons of changes in PQoL scores revealed greater improvement in the mesh group . Conclusion Both techniques were effective . Anatomical efficacy was superior in the mesh group regarding the anterior compartment ; quality of life changes were also greater in the mesh group . Complications were significantly higher in the mesh group Introduction and hypothesisThe aim of the study was to compare the efficacy and safety of transvaginal trocar-guided polypropylene mesh insertion with traditional colporrhaphy for treatment of anterior vaginal wall prolapse . Methods This is a r and omized controlled trial in which women with advanced anterior vaginal wall prolapse , at least stage II with Ba ≥ + 1 cm according to the Pelvic Organ Prolapse Quantification ( POP-Q ) classification , were r and omly assigned to have either anterior colporrhaphy ( n = 39 ) or repair using trocar-guided transvaginal mesh ( n = 40 ) . The primary outcome was objective cure rate of the anterior compartment ( point Ba ) assessed at the 12-month follow-up visit , with stages 0 and I defined as anatomical success . Secondary outcomes included quantification of other vaginal compartments ( POP-Q points ) , comparison of quality of life by the prolapse quality of life ( P-QOL ) question naire , and complication rate between the groups after 1 year . Study power was fixed as 80 % with 5 % cutoff point ( p < 0.05 ) for statistical significance . Results The groups were similar regarding demographic and clinical preoperative parameters . Anatomical success rates for colporrhaphy and repair with mesh placement groups were 56.4 vs 82.5 % ( 95 % confidence interval 0.068–0.54 ) , respectively , and the difference between the groups was statistically significant ( p = 0.018 ) . Similar total complication rates were observed in both groups , with tape exposure observed in 5 % of the patients . There was a significant improvement in all P-QOL domains as a result of both procedures ( p < 0.001 ) , but they were not distinct between groups ( p > 0.05 ) . Conclusions Trocar-guided transvaginal synthetic mesh for advanced anterior POP repair is associated with a higher anatomical success rate for the anterior compartment compared with traditional colporrhaphy . Quality of life equally improved after both techniques . However , the trial failed to detect differences in P-QOL scores and complication rates between the groups OBJECTIVE To compare the use of polypropylene mesh ( PM ) and the traditional anterior vaginal wall colporraphy in women with anterior vaginal wall prolapse ( AVWP ) using objective and subjective tests and evaluation of quality of life ( QoL ) . MATERIAL S AND METHODS One hundred women were r and omly distributed in two preoperatory groups . The first group ( mesh ) ( n = 45 ) received a PM implant and the control group ( n = 55 ) was su bmi tted to traditional colporraphy . Postoperatory follow-up was done after 12 months . The primary objective was the correction of the Ba point ≤ -2 POP-Q ( Pelvic Organ Prolapse Quantification System ) and the secondary objective was the improvement of vaginal symptoms and QoL through ICIQ-VS ( International Consultation on Incontinence Question naire - Vaginal Symptoms ) . Complications related to the use of PM or not were also described . RESULTS There was a significant difference between all POP-Q measures of pre- and postoperatory periods of each group in particular . There was a significant difference of the Ba point of the postoperatory period between the Mesh and Control group . The mean of Ba point in the Mesh group was statistically lower than of the Control group , depicting the better anatomical result of the first group . Both techniques improved vaginal symptoms and QoL. The most frequent complication of the Mesh group was prepubic hematoma in the perioperative period . In 9.3 % of the cases treated with mesh it was observed PM exposition at the anterior vaginal wall after 12 months , being most of them treated clinical ly . CONCLUSION The treatment of AVWP significantly improved the Ba point in the Mesh group in comparison to the Control group . There were no differences of the vaginal symptoms and QoL between the two groups after 12 months . There were few and low grade complications on both groups The aim of this study was to compare the efficiency of polypropylene mesh surgery with the site-specific repair surgeries in the treatment of cystocoeles . We r and omized 90 patients into two groups according to a computer-based program . After a 12-month ( mean ) follow up , we noticed that the polypropylene mesh surgery yielded good anatomical results . Acceptable anatomical cure rates were 91 and 72 % in the mesh surgery group and site-specific surgery group , respectively . There were three cases ( 6.9 % ) of mesh erosion . One case of urinary retention and two cases of de novo dyspareunia were seen in the mesh surgery group . De novo stress urinary incontinence developed in three patients in the site-specific surgery group . We concluded that surgery with light polypropylene mesh ( Sofradim ® , Parietene ) is superior to the site-specific surgery in the treatment of cystocoeles OBJECTIVE : To present 3-month outcomes of a double-blind , multicenter r and omized controlled trial comparing traditional vaginal prolapse surgery without mesh with vaginal surgery with mesh . METHODS : Women with pelvic organ prolapse quantification prolapse stages 2–4 were r and omized to vaginal colpopexy repair with mesh or traditional vaginal colpopexy without mesh . The primary outcome measure was objective treatment success ( pelvic organ prolapse quantification stage 1 or lower ) at 3 months . Secondary outcome measures included quality -of-life variables and complication rates . RESULTS : Sixty-five women were recruited from January 2007 to August 2009 , when the study was halted due to predetermined stopping criteria for vaginal mesh erosion at a median follow-up of 9.7 months ( range , 2.4–26.7 months ) . Thirty-two women underwent mesh colpopexy ( 24 anterior mesh , eight total mesh ) , and 33 women had vaginal colpopexies without mesh ( primarily uterosacral ligament suspension ) and concurrent colporrhaphy . There were no statistically significant baseline differences between the mesh and no-mesh groups with respect to demographics , menopausal status , and race . Analysis of the mesh and no-mesh women found no difference with respect to overall recurrence ( mesh : 19 [ 59.4 % ] compared with no mesh : 24 [ 70.4 % ] , P=.28 ) . There were five ( 15.6 % ) vaginal mesh erosions . Two cystotomies and one blood transfusion occurred in the Output:	The review showed differences in each step of the procedure , in perioperative care , in anesthesia and in surgeon ’ experience . Conclusion Our results highlight the problems concerning AC with the great range in postoperative outcomes . There is diversity in the anatomical structures used in the repair , in perioperative care and in the procedure itself
MS2761	*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 effectiveness of screening for liver cancer in reducing mortality from the disease in a high-risk population in China . Setting : A r and omised controlled trial was carried out among men aged 30 - 69 who were chronic carriers of hepatitis-B virus ( HBsAg positive ) during the period 1989 - 1995 in Qidong county , Jiangsu Province , China . Methods : 5581 HBsAg carriers were identified by population screening and r and omly assigned to a screening group ( group A , 3712 men ) , and controls ( group B , 1869 men ) . Screening was planned to be six monthly alpha-fetoprotein ( AFP ) assays , with follow-up of subjects having an abnormal ( ≥20 μg/l ) test . All subjects were followed up for liver cancer and /or death until 31 December 1995 . Results : The overall sensitivity and specificity of the programme was 55.3 % and 86.5 % , respectively ; in subjects who complied with all scheduled screening tests , the values were 80.0 % and 80.9 % . Three hundred and seventy-four primary liver cancer ( PLC ) cases were diagnosed . The percentage of cases in stage I was significantly higher in group A ( 29.6 % ) than in group B ( 6.0 % ) . The one- , three- , and five-year relative survival rates were 23.7 % , 7.0 % , and 4.0 % in group A , and 9.7 % , 4.0 % , and 4.1 % in group B respectively , with no difference in five-year survival between the groups . The mortality rate in the screened group ( 1138 per 100,000 person-years ) was not significantly different from that in the controls ( 1114 per 100,000 ) . A Poisson regression model showed that the probability of death ( rate ratio ) in the screening group was 0.83 ( 95 % CI 0.68 - 1.03 ) relative to the control group . Conclusions : Screening with AFP result ed in earlier diagnosis of liver cancer , but the gain in lead time did not result in any overall reduction in mortality , because therapy for the patients found by screening was ineffective . Further studies using improved methods of screening , diagnosis and treatment are indicated BACKGROUND The European R and omized Study of Screening for Prostate Cancer was initiated in the early 1990s to evaluate the effect of screening with prostate-specific-antigen ( PSA ) testing on death rates from prostate cancer . METHODS We identified 182,000 men between the ages of 50 and 74 years through registries in seven European countries for inclusion in our study . The men were r and omly assigned to a group that was offered PSA screening at an average of once every 4 years or to a control group that did not receive such screening . The predefined core age group for this study included 162,243 men between the ages of 55 and 69 years . The primary outcome was the rate of death from prostate cancer . Mortality follow-up was identical for the two study groups and ended on December 31 , 2006 . RESULTS In the screening group , 82 % of men accepted at least one offer of screening . During a median follow-up of 9 years , the cumulative incidence of prostate cancer was 8.2 % in the screening group and 4.8 % in the control group . The rate ratio for death from prostate cancer in the screening group , as compared with the control group , was 0.80 ( 95 % confidence interval [ CI ] , 0.65 to 0.98 ; adjusted P=0.04 ) . The absolute risk difference was 0.71 death per 1000 men . This means that 1410 men would need to be screened and 48 additional cases of prostate cancer would need to be treated to prevent one death from prostate cancer . The analysis of men who were actually screened during the first round ( excluding subjects with noncompliance ) provided a rate ratio for death from prostate cancer of 0.73 ( 95 % CI , 0.56 to 0.90 ) . CONCLUSIONS PSA-based screening reduced the rate of death from prostate cancer by 20 % but was associated with a high risk of overdiagnosis . ( Current Controlled Trials number , IS RCT N49127736 . BACKGROUND The effect of screening with prostate-specific-antigen ( PSA ) testing and digital rectal examination on the rate of death from prostate cancer is unknown . This is the first report from the Prostate , Lung , Colorectal , and Ovarian ( PLCO ) Cancer Screening Trial on prostate-cancer mortality . METHODS From 1993 through 2001 , we r and omly assigned 76,693 men at 10 U.S. study centers to receive either annual screening ( 38,343 subjects ) or usual care as the control ( 38,350 subjects ) . Men in the screening group were offered annual PSA testing for 6 years and digital rectal examination for 4 years . The subjects and health care providers received the results and decided on the type of follow-up evaluation . Usual care sometimes included screening , as some organizations have recommended . The numbers of all cancers and deaths and causes of death were ascertained . RESULTS In the screening group , rates of compliance were 85 % for PSA testing and 86 % for digital rectal examination . Rates of screening in the control group increased from 40 % in the first year to 52 % in the sixth year for PSA testing and ranged from 41 to 46 % for digital rectal examination . After 7 years of follow-up , the incidence of prostate cancer per 10,000 person-years was 116 ( 2820 cancers ) in the screening group and 95 ( 2322 cancers ) in the control group ( rate ratio , 1.22 ; 95 % confidence interval [ CI ] , 1.16 to 1.29 ) . The incidence of death per 10,000 person-years was 2.0 ( 50 deaths ) in the screening group and 1.7 ( 44 deaths ) in the control group ( rate ratio , 1.13 ; 95 % CI , 0.75 to 1.70 ) . The data at 10 years were 67 % complete and consistent with these overall findings . CONCLUSIONS After 7 to 10 years of follow-up , the rate of death from prostate cancer was very low and did not differ significantly between the two study groups . ( Clinical Trials.gov number , NCT00002540 . PURPOSE This clinical trial is aim ed at evaluating the impact of prostate cancer screening on cancer-specific mortality . SUBJECTS AND METHODS Forty-six thous and four hundred and eighty-six ( 46,486 ) men aged 45 - 80 years registered in the electoral roll of the Quebec city area were r and omized in 1988 between screening and no screening . Screening included measurement of serum prostatic specific antigen ( PSA ) using 3.0 ng/ml as upper limit of normal and digital rectal examination ( DRE ) at first visit . At follow-up visits , serum PSA only was used . RESULTS Seventy-four ( 74 ) deaths from prostate cancer occurred in the 14,231 unscreened controls while 10 deaths were observed in the screened group of 7,348 men during the first 11 years following r and omization . Median follow-up of screened men was 7.93 years . A Cox proportional hazards model of the age at death from prostate cancer shows a 62 % reduction ( P < 0.002 , Fisher 's exact test ) of cause-specific mortality in the screened men ( P = 0.005 ) . These results are in agreement with the continuous decrease of prostate cancer mortality observed in North America Purpose Screening for hepatocellular carcinoma ( HCC ) has been conducted for over 20 years , but there is no conclusive evidence that screening may reduce HCC mortality . The aim of this study was to assess the effect of screening on HCC mortality in people at increased risk . Methods This study included 18,816 people , aged 35–59 years with hepatitis B virus infection or a history of chronic hepatitis in urban Shanghai , China . Participants were r and omly allocated to a screening ( 9,373 ) or control ( 9,443 ) group . Controls received no screening and continued to use health-care facilities . Screening group participants were invited to have an AFP test and ultrasonography examination every 6 months . Screening was stopped in December 1997 ; by that time screening group participants had been offered five to ten times . All participants were followed up until December 1998 . The primary outcome measure was HCC mortality . Results The screened group completed 58.2 percent of the screening offered . When the screening group was compared to the control group , the number of HCC was 86 versus 67 ; sub clinical HCC being 52 ( 60.5 % ) versus 0 ; small HCC 39 ( 45.3 % ) versus 0 ; resection achieved 40 ( 46.5 % ) versus 5 ( 7.5 % ) ; 1- , 3,- , and 5-year survival rate 65.9 % , 52.6 % , 46.4 % versus 31.2 % , 7.2 % , 0 , respectively . Thirty-two people died from HCC in the screened group versus 54 in the control group , and the HCC mortality rate was significantly lower in the screened group than in controls , being 83.2/100,000 and 131.5/100,000 , respectively , with a mortality rate ratio of 0.63 ( 95%CI 0.41–0.98 ) . Conclusions Our finding indicated that biannual screening reduced HCC mortality by 37 % Stored sample s from women in the Stockholm screening study were reassayed for CA125II ( Centocor , Malvern , PA ) and OVX1 . The postmenopausal women older than age 50 without ovarian cancer were r and omly split into a training set to develop a screening test based on longitudinal marker levels and a second set to vali date the test . The CA125II data from each woman is summarized by the slope and intercept from a linear regression of log(CAl25II ) on time since first sample . The slope versus the intercept for the training set and the ovarian cancer cases formed a bivariate scatter plot . A curve was drawn on the scatter plot that separated most of the women with ovarian cancer from all other women ; it delineated a screening test . The specificity of this test was examined on the validation set with a specificity of 99.8 % . Bayes ' theorem was used to calculate the risk of ovarian cancer ( ROC ) based on the intercept , slope , and assay variability . It is important to account for assay variability because it can produce large slopes over short periods of time . The maximum risk , which identified 83 % ( 5 of 6 ) of the ovarian cancers detected within a year of last assay , was applied as a test to the training set and confirmed a high specificity of 99.7 % . With this specificity and sensitivity , the ROC algorithm using the CA125II assay has an estimated positive predictive value of 16 % , substantially greater than the positive predictive value based on a single assay . Further study is planned to confirm the sensitivity of this approach . Cancer 1995 ; 76:2004‐10 New stool tests may be promising tools for future colorectal cancer ( CRC ) screening . The aim of this review was to summarize current evidence of performance characteristics and practicalness in a population ‐based screening setting of recently developed stool tests . The MEDLINE data base was search ed for relevant articles published until July 2004 . Studies were included if they comprised more than 10 cases and more than 10 controls . Details on study population , performance characteristics and stool collection procedure were taken into account . Overall , 29 studies , mostly retrospective , were included , investigating 17 different stool markers or marker combinations . Underlying study population s were very heterogeneous and mostly very small . Half of the studies reported sensitivity for adenomas in addition to sensitivity for CRC , and fewer than half reported sensitivity by tumor stage or location . Performance characteristics of stool tests varied to a large extent . For most DNA‐based markers , specificity was about 95 % or higher , but sensitivity was mostly low even for invasive CRC . More studies with larger sample sizes were done for protein‐based markers , which typically had lower specificity . In most studies , stool sample s were frozen within a rather short time period after defecation . While promising performance characteristics have been reported for some tests , more pervasive evidence from larger , prospect ively design ed studies , which also consider aspects of practicalness , e.g. , the possibility of mailing the sample s , is needed . © 2005 Wiley‐Liss , PURPOSE To evaluate prevalence screening in the first prospect i ve trial of a new ovarian cancer screening ( OCS ) strategy ( risk of ovarian cancer or ROC algorithm ) on the basis of age and CA125 profile . PATIENTS AND METHODS Postmenopausal women , > or = 50 years were r and omly assigned to a control group or screen group . Screening involved serum CA125 , interpreted using the ROC algorithm . Participants with normal results returned to annual screening ; those with intermediate results had repeat CA125 testing ; and those with elevated values underwent transvaginal ultrasound ( TVS ) . Women with abnormal or persistently equivocal TVS were referred for a gynecologic opinion . RESULTS Thirteen thous and five hundred eighty-two women were recruited . Of 6,682 women r and omly assigned to screening , 6, Output:	Of these markers , only the use of FOBT in screening for CRC has been shown to reduce mortality from cancer . This lack of sensitivity and specificity when combined with the low prevalence of cancers in the general population means that most biomarkers , if used alone , have a low positive predictive value in screening asymptomatic population s. Indeed , it is the low prevalence of cancer in the general population that prohibits most biomarkers from being used alone , in screening for cancer ( 4,5 ) .
MS2762	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND AND OBJECTIVE Postoperative renal impairment is a recognized complication of infrarenal aortic cross-clamping . Our hypothesis was that the renal vasodilating and natriuretic effects of fenoldopam mesylate , a selective dopamine ( DA1 ) agonist , would preserve renal function in patients undergoing elective infrarenal aortic cross-clamping . METHODS A prospect i ve , r and omized , double blind controlled clinical trial was performed . Twenty-eight ASA II-III patients undergoing elective aortic surgery requiring infrarenal aortic cross-clamping were studied . According to r and om allocation , patients received either fenoldopam ( 0.1 microg kg(-1 ) min(-1 ) ) or placebo intravenously prior to surgical skin incision until release of the aortic clamp . Plasma creatinine , creatinine clearance , urinary output , fractional excretion of sodium , and free water clearance were measured : ( a ) prior to admission to hospital ; ( b ) during the period from insertion of the urinary catheter until application of the aortic cross-clamp ; ( c ) during the period of aortic cross-clamping ; ( d ) 0 - 4 h , and ( e ) 4 - 8 h after release of the clamp and on days 1 , 2 , 3 , and 5 postoperatively . RESULTS Fenoldopam ( 0.1 microg kg(-1)min(-1 ) ) administration was not associated with haemodynamic instability . On application of the aortic cross-clamp creatinine clearance decreased significantly in the placebo ( 83 + /- 20 to 42 + /- 29 mL min(-1 ) ( mean + /- SD ) ) ( P < 0.01 ) but not in the fenoldopam group , and this decrease persisted for at least 8 h after release of the cross-clamp ( 83 + /- 20 to 54 + /- 33 mL min(-1 ) ( mean + /- SD ) ) ( P < 0.05 ) . Plasma creatinine concentration increased significantly from baseline on the first postoperative day in the placebo group ( 87 + /- 12 to 103 + /- 28 micromolL(-1 ) ( mean + /- SD ) ) ( P < 0.01 ) but not in the fenoldopam group . CONCLUSIONS These findings are consistent with the hypothesis that fenoldopam possesses a renoprotective effect during and after infrarenal aortic cross-clamping Objective : Fenoldopam mesylate is a selective dopamine-1 agonist , with no effect on dopamine-2 and & agr;1 receptors , producing a selective renal vasodilation . This may favor the kidney oxygen supply/dem and ratio and prevent acute renal failure . The aim of the study was to investigate if fenoldopam can provide greater benefit than low-dose dopamine in early renal dysfunction of critically ill patients . Design : Prospect i ve , multiple-center , r and omized , controlled trial . Setting : University and city hospital intensive care units . Patients : One hundred adult critically ill patients with early renal dysfunction ( intensive care unit stay < 1 wk , hemodynamic stability , and urine output ≤0.5 mL/kg over a 6-hr period and /or serum creatinine concentration ≥1.5 mg/dL and ≤ 3.5 mg/dL ) . Interventions : Patients were r and omized to receive 2 & mgr;g/kg/min dopamine ( group D ) or 0.1 & mgr;g/kg/min fenoldopam mesylate ( group F ) . Drugs were administered as continuous infusion over a 4-day period . Measurements and Main Results : Systemic hemodynamic and renal function variables were recorded daily . The two groups were well matched at enrollment for illness severity and hemodynamic and renal dysfunction . No differences in heart rate or systolic , diastolic , or mean arterial pressure were observed between groups . Fenoldopam produced a more significant reduction in creatinine values compared with dopamine after 2 , 3 , and 4 days of infusion ( change from baseline at time 2 , −0.32 vs. −0.03 mg/dL , p = .047 ; at time 3 , −0.45 vs. −0.09 mg/dL , p = .047 ; and at time 4 , −.041 vs. −0.09 mg/dL , p = .02 , in groups F and D , respectively ) . The maximum decrease in creatinine compared with baseline was significantly greater in group F than group D ( −0.53 ± 0.47 vs. −0.34 ± 0.38 mg/dL , p = .027 ) . Moreover , 66 % of patients in group F had a creatinine decrease > 10 % of the baseline value at the end of infusion , compared with only 46 % in dopamine group ( chi-square = 4.06 , p = .04 ) . Total urinary output during drug infusion was not significantly different between groups . After 1 day , urinary output was lower in group F compared with group D ( p < .05 ) . Conclusions : In critically ill patients , a continuous infusion of fenoldopam at 0.1 & mgr;g/kg/min does not cause any clinical ly significant hemodynamic impairment and improves renal function compared with renal dose dopamine . In the setting of acute early renal dysfunction , before severe renal failure has occurred , the attempt to reverse renal hypoperfusion with fenoldopam is more effective than with low-dose dopamine To test the relative effects on serum creatinine ( CRE ) , blood urea nitrogen ( BUN ) , and urine output of small-dose dopamine and fenoldopam in patients undergoing liver transplantation , we r and omized 43 patients to 1 of 2 continuous infusions over 48 h , starting with anesthesia induction : fenoldopam , 0.1 & mgr;g · kg−1 · min−1 or dopamine , 2 & mgr;g · kg−1 · min−1 . We used predetermined hemodynamic and intravascular volume goals ( intrathoracic blood volume index 800–1000 mL/m2 , extravascular lung water index < 7 mL/kg ) to manage patients with an algorithm for use of mannitol and furosemide to maintain urine output > 1 mL · kg−1 · h−1 . At postoperative day 3 , the median CRE increase was 0.2 mg/dL ( interquartile range [ IQR ] −0.2–0.5 ) with fenoldopam and 0.5 mg/dL ( IQR 0.3–0.9 , P = 0.004 ) in the dopamine group . The BUN increase was median 2 mg/dL ( IQR −2–8 ) versus 8.5 mg/dL ( IQR 5–12 , P = 0.01 ) , respectively , with fenoldopam versus dopamine . Urine output was similar ; however , significantly fewer fenoldopam patients required furosemide compared with dopamine patients ( median 1 [ IQR 0–3 ] versus 3 [ IQR 2–4 ] , respectively , P = 0.003 ) . The hemodynamic effects of dopamine and fenoldopam were similar . Compared with dopamine , in the setting of liver transplantation , fenoldopam is associated with better CRE and BUN values Impairment of renal and splanchnic perfusion during and after cardiopulmonary bypass may be responsible for acute renal failure and endotoxin‐mediated systemic inflammation , respectively . We hypothesised that fenoldopam , a selective dopamine receptor agonist , would preserve renal function after cardiopulmonary bypass through its selective renal vasodilatory and natriuretic effects , and increase gastrointestinal mucosal perfusion by selective splanchnic vasodilation . We examined the effects of fenoldopam on haemodynamic parameters , creatinine clearance , fractional excretion of sodium , urine output , free water clearance and gastric mucosal pH in 31 patients undergoing elective coronary revascularisation . Patients were r and omly assigned to receive continuous infusions of fenoldopam 0.1 µg.kg−1.min−1 ( n = 16 ) or placebo ( n = 15 ) . Renal parameters were measured : during a 24‐h period before hospital admission , during cardiopulmonary bypass , from completion of cardiopulmonary bypass until 4 h later , from 4 to 8 h after cardiopulmonary bypass , and from 8 to 14 h after cardiopulmonary bypass . Gastric intramucosal pH was measured using a gastric tonometer before , during and after cardiopulmonary bypass . In the placebo group , but not the fenoldopam group , mean ( SD ) creatinine clearance decreased after separation from cardiopulmonary bypass , from 107 ( 36 ) to 71 ( 22 ) ml.min−1 ( p < 0.01 ) and from 107 ( 36 ) to 79 ( 26 ) ml.min−1 ( p < 0.01 ) for the 0–4 h and 4–8 h intervals after cardiopulmonary bypass , respectively . Changes in intramucosal pH were similar in both groups . The findings are consistent with the hypothesis that fenoldopam possesses a renoprotective effect in patients undergoing cardiopulmonary bypass Background : Inadequate splanchnic perfusion in septic shock is associated with increased morbidity and mortality . As result of splanchnic ischemia , mucosal permeability increases . Considering the implication of improved mucosal perfusion in terms of maintenance of mucosal barrier integrity , dopamine-1 receptor stimulation could be helpful in septic shock . The goal of the current study was to determine the effects of fenoldopam on systemic hemodynamic parameters and gastric mucosal perfusion in patients with septic shock . Furthermore , the authors tested the hypothesis that the addition of fenoldopam ( 0.1 & mgr;g · kg−1 · min−1 ) to a combination of norepinephrine and dobutamine ( 5 & mgr;g · kg−1 · min−1 ) may improve gastric mucosal perfusion in septic shock . Methods : Patients with septic shock were r and omized to a double-blind 2-h infusion of fenoldopam ( n = 20 ) or placebo ( n = 20 ) . Each group received dobutamine ( 5 & mgr;g · kg−1 · min−1 ) , and the dosage of norepinephrine was adjusted to achieve a mean arterial pressure between 70 and 80 mmHg . A laser-Doppler probe and tonometer were introduced into the gastric lumen . Results : A significant increase in gastric mucosal perfusion , detected by laser-Doppler flowmetry , was observed in the group treated with fenoldopam ( P < 0.05 ) . In addition , this increase in microcirculatory flow occurred despite the fact that systemic flow remained unchanged . Differences in gastroarterial partial pressure of carbon dioxide values were not statistically significant in the fenoldopam and placebo groups . Conclusions : The study showed that , for the same mean arterial pressure , short-term fenoldopam infusion increased gastric mucosal perfusion in patients with septic shock CONTEXT The development of contrast-induced nephropathy in patients undergoing invasive cardiac procedures is associated with a marked increase in cardiovascular morbidity and mortality . Fenoldopam mesylate , a specific agonist of the dopamine-1 receptor , preserves renal blood flow after iodinated contrast administration and has shown promise in ameliorating contrast nephropathy in previous observational and small r and omized trials . OBJECTIVE To examine the efficacy of fenoldopam mesylate in preventing contrast nephropathy after invasive cardiovascular procedures . DESIGN Prospect i ve , placebo-controlled , double-blind , multicenter r and omized trial with serial serum creatinine levels measured at a central biochemistry laboratory ( at baseline and 1 , 24 , 48 , and 72 to 96 hours after study drug administration ) and 30-day clinical follow-up . PATIENTS AND SETTING Between March 2001 and July 2002 , 315 patients with creatinine clearance less than 60 mL/min ( 1.00 mL/s ) at 28 centers in the United States were r and omized to receive fenoldopam mesylate ( n = 157 ) or placebo ( n = 158 ) . INTERVENTIONS Patients were hydrated and r and omized to receive intravenous fenoldopam ( 0.05 microg/kg/min titrated to 0.10 microg/kg/min ) vs matching placebo , starting 1 hour prior to angiography and continuing for 12 hours . MAIN OUTCOME MEASURE Contrast-induced nephropathy , defined as an increase of 25 % or more in serum creatinine level within 96 hours postprocedure . RESULTS Mean ( SD ) patient age was 70 ( 11 ) years , and 49 % had diabetes mellitus . Mean ( SD ) baseline creatinine clearance was 29.0 ( 10.0 ) mL/min ( 0.48 [ 0.16 ] mL/s ) ( range , 7.5 - 56.8 mL/min [ 0.12 - 0.94 m Output:	This analysis suggests that fenoldopam reduces the need for renal replacement and mortality in patients with acute kidney injury .
MS2763	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE This study aim ed to evaluate the abuse potential and cognitive effects of nabiximols ( Sativex , GW Pharma Ltd. Salisbury , UK ) , an oromucosal spray primarily containing delta‐9‐tetrahydrocannabinol ( THC ) and cannabidiol ( CBD ) . METHODS This was a single‐dose , r and omized , double‐blind , crossover study comparing nabiximols ( 4 , 8 , and 16 consecutive sprays : 10.8 , 21.6 , and 43.2 mg THC , respectively ) with dronabinol 20 and 40 mg ( synthetic THC : Marinol , Solvay Pharmaceuticals , Brussels , Belgium ) and matching placebos in 23 recreational cannabis users . Subjective and cognitive/psychomotor measures were administered over 24 h post‐dose . RESULTS Dronabinol was significantly different from placebo on abuse potential measures , thereby confirming study validity . Nabiximols 10.8 mg was not significantly different from placebo on primary measures but was different on some secondary measures . Nabiximols 21.6 mg was significantly greater than placebo on some primary / secondary measures , whereas nabiximols 43.2 mg showed significant effects on most measures . Nabiximols 10.8 mg was significantly lower than dronabinol doses on most measures ( p < 0.05 ) . Dronabinol 20 mg effects were numerically higher than nabiximols 21.6 mg but were statistically significant only for some measures . Dronabinol 40 mg and nabiximols 43.2 mg were generally not statistically different . CONCLUSIONS Both dronabinol and nabiximols had significant abuse potential compared with placebo at higher doses . Nabiximols showed similar or slightly less abuse potential compared with dronabinol . Therefore , the abuse potential of nabiximols should be no higher than that of dronabinol BACKGROUND Our previous research suggested the involvement of γ-aminobutyric acid ( GABA ) , in particular the GABAB receptor subtype , in the interoceptive effects of Δ(9)-tetrahydrocannabinol ( Δ(9)-THC ) . The aim of the present study was to determine the potential involvement of the GABAA receptor subtype by assessing the separate and combined effects of the GABAA positive allosteric modulator diazepam and Δ(9)-THC using pharmacologically selective drug-discrimination procedures . METHODS Ten cannabis users learned to discriminate 30 mg oral Δ(9)-THC from placebo and then received diazepam ( 5 and 10 mg ) , Δ(9)-THC ( 5 , 15 and 30 mg ) and placebo , alone and in combination . Self-report , task performance and physiological measures were also collected . RESULTS Δ(9)-THC functioned as a discriminative stimulus , produced subjective effects typically associated with cannabinoids ( e.g. , High , Stoned , Like Drug ) and elevated heart rate . Diazepam alone impaired performance on psychomotor performance tasks and increased ratings on a limited number of self-report question naire items ( e.g. , Any Effect , Se date d ) , but did not substitute for the Δ(9)-THC discriminative stimulus or alter the Δ(9)-THC discrimination dose-response function . Similarly , diazepam had limited impact on the other behavioral effects of Δ(9)-THC . CONCLUSIONS These results suggest that the GABAA receptor subtype has minimal involvement in the interoceptive effects of Δ(9)-THC , and by extension cannabis , in humans Rationale Long-term heavy cannabis use can result in memory impairment . Adolescent users may be especially vulnerable to the adverse neurocognitive effects of cannabis . Objectives and methods In a cross-sectional and prospect i ve neuropsychological study of 181 adolescents aged 16–20 ( mean 18.3 years ) , we compared performance indices from one of the most widely used measures of learning and memory — the Rey Auditory Verbal Learning Test — between cannabis users ( n = 52 ; mean 2.4 years of use , 14 days/month , median abstinence 20.3 h ) , alcohol users ( n = 67 ) and non-user controls ( n = 62 ) matched for age , education and premorbid intellectual ability ( assessed prospect ively ) , and alcohol consumption for cannabis and alcohol users . Results Cannabis users performed significantly worse than alcohol users and non-users on all performance indices . They recalled significantly fewer words overall ( p < 0.001 ) , demonstrating impaired learning ( p < 0.001 ) , retention ( p < 0.001 ) and retrieval ( p < 0.05 ) ( Cohen ’s d 0.43–0.84 ) . The degree of impairment was associated with the duration , quantity , frequency and age of onset of cannabis use , but was unrelated to alcohol exposure or other drug use . No gender effects were detected and the findings remained after controlling for premorbid intellectual ability . An earlier age of onset of regular cannabis use was associated with worse memory performance after controlling for extent of exposure to cannabis . Conclusions Despite relatively brief exposure , adolescent cannabis users relative to their age-matched counterparts demonstrated similar memory deficits to those reported in adult long-term heavy users . The results indicate that cannabis adversely affects the developing brain and reinforce concerns regarding the impact of early exposure Recent reports show that fewer adolescents believe that regular cannabis use is harmful to health . Concomitantly , adolescents are initiating cannabis use at younger ages , and more adolescents are using cannabis on a daily basis . The purpose of the present study was to test the association between persistent cannabis use and neuropsychological decline and determine whether decline is concentrated among adolescent-onset cannabis users . Participants were members of the Dunedin Study , a prospect i ve study of a birth cohort of 1,037 individuals followed from birth ( 1972/1973 ) to age 38 y. Cannabis use was ascertained in interviews at ages 18 , 21 , 26 , 32 , and 38 y. Neuropsychological testing was conducted at age 13 y , before initiation of cannabis use , and again at age 38 y , after a pattern of persistent cannabis use had developed . Persistent cannabis use was associated with neuropsychological decline broadly across domains of functioning , even after controlling for years of education . Informants also reported noticing more cognitive problems for persistent cannabis users . Impairment was concentrated among adolescent-onset cannabis users , with more persistent use associated with greater decline . Further , cessation of cannabis use did not fully restore neuropsychological functioning among adolescent-onset cannabis users . Findings are suggestive of a neurotoxic effect of cannabis on the adolescent brain and highlight the importance of prevention and policy efforts targeting adolescents Worldwide cannabis dependence is increasing , as is the concentration of Δ9-tetrahydrocannabinol ( THC ) in street cannabis . At the same time , the concentration of the second most abundant cannabinoid in street cannabis , cannabidiol ( CBD ) , is decreasing . These two cannabinoids have opposing effects both pharmacologically and behaviorally when administered in the laboratory . No research has yet examined how the ratio of these constituents impacts on the appetitive/reinforcing effects of cannabis in humans . A total of 94 cannabis users were tested 7 days apart , once while non-intoxicated and once while acutely under the influence of their own chosen smoked cannabis on dependence-related measures . Using an unprecedented methodology , a sample of cannabis ( as well as saliva ) was collected from each user and analyzed for levels of cannabinoids . On the basis of CBD : THC ratios in the cannabis , individuals from the top and bottom tertiles were directly compared on indices of the reinforcing effects of drugs , explicit liking , and implicit attentional bias to drug stimuli . When intoxicated , smokers of high CBD : THC strains showed reduced attentional bias to drug and food stimuli compared with smokers of low CBD : THC . Those smoking higher CBD : THC strains also showed lower self-rated liking of cannabis stimuli on both test days . Our findings suggest that CBD has potential as a treatment for cannabis dependence . The acute modulation of the incentive salience of drug cues by CBD may possibly generalize to a treatment for other addictive disorders Introduction Cannabinoids produce a spectrum of effects in humans including euphoria , cognitive impairments , psychotomimetic effects , and perceptual alterations . The extent to which dopaminergic systems contribute to the effects of Δ-9-tetrahydrocannabinol ( Δ-9-THC ) remains unclear . This study evaluated whether pretreatment with a dopamine receptor antagonist altered the effects of Δ-9-THC in humans . Material s and methods In a 2-test-day double-blind study , 28 subjects including healthy subjects ( n = 17 ) and frequent users of cannabis ( n = 11 ) were administered active ( 0.057 mg/kg ) or placebo oral haloperidol in r and om order followed 90 and 215 min later by fixed order intravenous administration of placebo ( vehicle ) and active ( 0.0286 mg/kg ) Δ-9-THC , respectively . Results Consistent with previous reports , intravenous Δ-9-THC produced psychotomimetic effects , perceptual alterations , and subjective effects including “ high . ” Δ-9-THC also impaired verbal recall and attention . Haloperidol pretreatment did not reduce any of the behavioral effects of Δ-9-THC . Haloperidol worsened the immediate free and delayed free and cued recall deficits produced by Δ-9-THC . Haloperidol and Δ-9-THC worsened distractibility and vigilance . Neither drug impaired performance on a motor screening task , the Stockings of Cambridge task , or the delayed match to sample task . Frequent users had lower baseline plasma prolactin levels and blunted Δ-9-THC induced memory impairments . Conclusions The deleterious effects of haloperidol pretreatment on the cognitive effects of Δ-9-THC are consistent with the pre clinical literature in suggesting crosstalk between DAergic and CBergic systems . However , it is unlikely that DA D2 receptor mechanisms play a major role in mediating the psychotomimetic and perceptual altering effects of Δ-9-THC . Further investigation is warranted to underst and the basis of the psychotomimetic effects of Δ-9-THC and to better underst and the crosstalk between DAergic and CBergic systems Rationale Δ9-Tetrahydrocannabinol ( THC ) is the main active constituent of cannabis . In recent years , the average THC content of some cannabis cigarettes has increased up to approximately 60 mg per cigarette ( 20 % THC cigarettes ) . Acute cognitive and psychomotor effects of THC among recreational users after smoking cannabis cigarettes containing such high doses are unknown . Objectives The objective of this study was to study the dose – effect relationship between the THC dose contained in cannabis cigarettes and cognitive and psychomotor effects for THC doses up to 69.4 mg ( 23 % ) . Material s and methods This double-blind , placebo-controlled , r and omised , four-way cross-over study included 24 non-daily male cannabis users ( two to nine cannabis cigarettes per month ) . Participants smoked four cannabis cigarettes containing 0 , 29.3 , 49.1 and 69.4 mg THC on four exposure days . Results The THC dose in smoked cannabis was linearly associated with a slower response time in all tasks ( simple reaction time , visuo-spatial selective attention , sustained attention , divided attention and short-term memory tasks ) and motor control impairment in the motor control task . The number of errors increased significantly with increasing doses in the short-term memory and the sustained attention tasks . Some participants showed no impairment in motor control even at THC serum concentrations higher than 40 ng/mL. High feeling and drowsiness differed significantly between treatments . Conclusions Response time slowed down and motor control worsened , both linearly , with increasing THC doses . Consequently , cannabis with high THC concentrations may be a concern for public health and safety if cannabis smokers are unable to titrate to a high feeling corresponding to a desired plasma THC level While the effects of cannabis use on retrospective memory have been extensively examined , only a limited number of studies have focused on the links between cannabis use and prospect i ve memory . We conducted two studies to examine the links between cannabis use and both time-based and event-based prospect i ve memory as well as potential mechanisms underlying these links . For the first study , 805 students completed an online survey design ed to assess cannabis consumption , problems with cannabis use indicative of a disorder , and frequency of experiencing prospect i ve memory failures . The results showed small to moderate sized correlations between cannabis consumption , problems with cannabis use , and prospect i ve memory . However , a series of mediation analyses revealed that correlations between problems with cannabis use and prospect i ve memory were driven by self-reported problems with retrospective memory . For the second study , 48 non-users ( who had never used cannabis ) , 48 experimenters ( who had used cannabis five or fewer times Output:	Verbal learning and memory and attention are most consistently impaired by acute and chronic exposure to cannabis . Psychomotor function is most affected during acute intoxication , with some evidence for persistence in chronic users and after cessation of use . Associations between poorer performance and a range of cannabis use parameters , including a younger age of onset , are frequently reported . Little further evidence has emerged for the development of tolerance to the acutely impairing effects of cannabis .
MS2764	*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 the rapidly growing body of literature on health-related quality of life ( HRQoL ) . placing the results in a context that is meaningful to clinicians and patients is often overlooked . OBJECTIVE This study sought to quantify the impact of irritable bowel syndrome ( IBS ) on HRQoL by comparing the Medical Outcomes Study 36-item Short-Form Health Survey ( SF-36 ) scores of IBS patients with normative US data and with the scores of patients having other chronic gastrointestinal ( GI ) and non-GI disorders . METHODS Two IBS reference groups were identified from the published literature : a largely untreated community sample of health maintenance organization ( HMO ) members ( N = 92 ) and a sample of patients with IBS recruited through clinics and in the community ( N = 140 ) . SF-36 scores for these groups were compared with published US population norms ( N = 2474 ) and with published scores for 3 other IBS sample s ( N = 464 ) ; a sample with other chronic GI disorders ( dyspepsia [ N = 126 ] , gastroesophageal reflux disease [ GERD ] [ N = 516 ] ) ; and sample s with other chronic episodic disorders ( asthma [ N = 375 ] , migraine [ N = 303 ] , panic disorder [ N = 73 ] , rheumatoid arthritis [ N = 693 ] ) . RESULTS The scores of patients in both IBS reference groups were significantly lower on several SF-36 domains than those of the US normative population ( P < 0.003 ) . Scores on several SF-36 scales were also significantly lower in the IBS reference groups compared with the GERD , asthma , and migraine sample s ( P < 0.003 ) . Depending on the IBS sample used , scores did not differ or were higher compared with those in the sample with dyspepsia . Relative to the sample s with panic disorder and rheumatoid arthritis , the IBS groups had significantly higher scores on most SF-36 domains ( P < 0.003 ) . Scores for the HMO reference group were generally higher than those for the clinic/community reference group . CONCLUSIONS Based on the results of this analysis , IBS is associated with impairment of HRQoL relative to US population norms and to population s with GERD , asthma , or migraine . HRQoL appears to be greater in patients with IBS than in those with panic disorder or rheumatoid arthritis , although the relative symptom severity in these sample s was not known Objective . This r and omized trial evaluated the therapeutic effect of emotional awareness training on the severity and frequency of pain in patients with irritable bowel syndrome ( IBS ) . Patients ’ level of alexithymia was also measured . Method . The study involved 100 patients diagnosed with IBS according to the Rome-III criteria . Patients ’ mean age was 34.98 years ( st and ard deviation 10.22 years ) and 60 % of the patients were female . Seventy eligible patients were assigned r and omly to one of two treatment groups . One group received st and ard symptom-oriented medical treatment only ( MT group ) , while the second group , termed the emotional awareness group ( EMT ) , was educated to increase conscious awareness of eight primary emotions in addition to receiving st and ard symptom-oriented medical treatment . This study was conducted over 20 months . All patients received 5 weeks of symptom-oriented medical treatment ; patients in the EMT group also had two emotion awareness training sessions and recorded their emotions in a daily diary . Sixty patients completed the study . Results . Patients with IBS scored significantly higher on all aspects of alexithymia compared with healthy controls . The severity of pain decreased significantly in both groups , with a larger percentage of the patients in the EMT group who completed the study having a significant decrease in pain ( 54 % in the EMT group vs. 36 % in the MT group ) ; this finding was replicated in an intent-to-treat analysis . The same results were observed for frequency of pain in patients who completed the study ( 59 % in the EMT group vs 43.4 % in the MT group ) , but this finding was not replicated in an intent-to-treat analysis . These patterns were not influenced by level of alexithymia , age , or gender . Conclusion . Adding emotional awareness training to medical treatment result ed in a better therapeutic response in abdominal pain in patients with IBS . ( Journal of Psychiatric Practice 2014;20:3–11 Background Internet-based cognitive behavior therapy ( ICBT ) has shown promising effects in the treatment of irritable bowel syndrome ( IBS ) . However , to date no study has used a design where participants have been sample d solely from a clinical population . We aim ed to investigate the acceptability , effectiveness , and cost-effectiveness of ICBT for IBS using a consecutively recruited sample from a gastroenterological clinic . Methods Sixty-one patients were r and omized to 10 weeks of ICBT ( n = 30 ) or a waiting list control ( n = 31 ) . The ICBT was guided by an online therapist and emphasized acceptance of symptoms through exposure and mindfulness training . Severity of IBS symptoms was measured with the Gastrointestinal symptom rating scale - IBS version ( GSRS-IBS ) . Patients in both groups were assessed at pre- and post-treatment while only the ICBT group was assessed 12 months after treatment completion . Health economic data were also gathered at all assessment points and analyzed using bootstrap sampling . Results Fifty of 61 patients ( 82 % ) completed the post-treatment assessment and 20 of 30 patients ( 67 % ) in the ICBT group were assessed at 12-month follow-up . The ICBT group demonstrated significantly ( p < .001 ) larger improvements on the IBS-related outcome scales than the waiting list group . The between group effect size on GSRS-IBS was Cohen 's d = 0.77 ( 95 % CI : 0.19 - 1.34 ) . Similar effects were noted on measures of quality of life and IBS-related fear and avoidance behaviors . Improvements in the ICBT group were maintained at 12-month follow-up . The ICBT condition was found to be more cost-effective than the waiting list , with an 87 % chance of leading to reduced societal costs combined with clinical effectiveness . The cost-effectiveness was sustained over the 12-month period . Conclusions ICBT proved to be a cost-effective treatment when delivered to a sample recruited from a gastroenterological clinic . However , many of the included patients dropped out of the study and the overall treatment effects were smaller than previous studies with referred and self-referred sample s. ICBT may therefore be acceptable and effective for only a subset of clinical patients . Study dropout seemed to be associated with severe symptoms and large impairment . Objective and empirically vali date d criteria to select which patients to offer ICBT should be developed . Trial Registration Clinical Trials.gov : OBJECTIVES : Gut-directed hypnotherapy has been found to be effective in irritable bowel syndrome ( IBS ) . However , r and omized , controlled studies are rare and few have been performed outside highly specialized research centers . The objective of this study was to study the effect of gut-directed hypnotherapy in IBS in different clinical setting s outside the traditional research units . METHODS : The study population included IBS patients refractory to st and ard management . In study 1 , patients were r and omized to receive gut-directed hypnotherapy ( 12 sessions , 1 h/week ) in psychology private practice s or supportive therapy , whereas patients were r and omized to receive gut-directed hypnotherapy in a small county hospital or to serve as waiting list controls in study 2 . Gastrointestinal symptom severity and quality of life were evaluated at baseline , at 3 months follow-up and after 1 year . RESULTS : We r and omized 138 IBS patients refractory to st and ard management , 90 in study 1 and 48 in study 2 . In both the studies , IBS-related symptoms were improved at 3 months in the gut-directed hypnotherapy groups ( P<0.05 ) , but not in the control groups ( ns ) . In study 1 , a significantly greater improvement of IBS-related symptom severity could be detected in the gut-directed hypnotherapy group than in the control group ( P<0.05 ) , and a trend in the same direction was seen in study 2 ( P=0.17 ) . The results seen at 3 months were sustained up to 1 year . CONCLUSIONS : Gut-directed hypnotherapy is an effective treatment alternative for patients with refractory IBS , but the effectiveness is lower when the therapy is given outside the highly specialized research centers Introduction The study aims to investigate two kinds of treatment in patients suffering from irritable bowel syndrome ( IBS ) and consequently compares its efficacy on improving the symptoms and mental health of patients ; one with just medical treatment and another through a combination of psychotherapy and medical treatment . Material and methods Applying general sampling , 50 IBS patients were selected from among those who used to refer to a Gastroenterology Clinic . After physical and mental evaluations based on ROME-II scale and SCL-90-R question naires , the subjects were r and omly superseded into : the control group with medical treatment and , the case group with a combination of medical and psychological treatments . The acquired data were then analyzed through t-test and Mann-Whitney U-test . Results The findings show that the mental health of patients receiving cognitive behavioral therapy along with the medical treatment was higher than those of the control group at post-test level . It was observed that the therapy reduces the disability caused by IBS . Comparatively , while the cognitive therapy and medical treatments cured 80 % of the patients , those receiving cognitive therapy alone showed an extensive reduction of symptoms . Conclusions Considering the role of cognitive behavioral therapy , it is therefore recommend that such patients be managed by a combined team of gastroenterologists and psychologists This study was conducted to evaluate the comparative effect of yogic and conventional treatment in diarrhea-predominant irritable bowel syndrome ( IBS ) in a r and omized control design . The patients were 22 males , aged 20–50 years , with confirmed diagnosis of diarrhea-predominant IBS . The conventional group ( n=12 , 1 dropout ) was given symptomatic treatment with loperamide 2–6 mg/day for 2 months , and the yogic intervention group ( n=9 ) consisted of a set of 12 asanas ( yogic poses , i.e. , Vajrasana , Shashankasana , Ushtrasana , Marjariasana , Padhastasana , Dhanurasana , Trikonasana in two variations , Pawanmuktasana , and Paschimottanasana ) along with Surya Nadi pranayama ( right-nostril breathing ) two times a day for 2 months . All participants were tested at three regular intervals , at the start of study —0 month , 1 month , and 2 months of receiving the intervention— and were investigated for bowel symptoms , autonomic symptoms , autonomic reactivity ( battery of five st and ard tests ) , surface electrogastrography , anxiety profile by Spielberger 's Self Evaluation Question naire , which evaluated trait and state anxiety . Two months of both conventional and yogic intervention showed a significant decrease of bowel symptoms and state anxiety . This was accompanied by an increase in electrophysiologically recorded gastric activity in the conventional intervention group and enhanced parasympathetic reactivity , as measured by heart rate parameters , in yogic intervention group . The study indicates a beneficial effect of yogic intervention over conventional treatment in diarrhea-predominant IBS One hundred two patients with irritable bowel syndrome were studied in a controlled trial of psychological treatment involving psychotherapy , relaxation , and st and ard medical treatment compared with st and ard medical treatment alone . Patients were only selected if their symptoms had not improved with st and ard medical treatment over the previous 6 months . At 3 months , the treatment group showed significantly greater improvement than the controls on both gastroenterologists ' and patients ' ratings of diarrhea and abdominal pain , but constipation changed little . Good prognostic factors included overt psychiatric symptoms and intermittent pain exacerbated by stress , whereas those with constant abdominal pain were helped little by this treatment . This study has demonstrated that psychological treatment is feasible and effective in two thirds of those patients with irritable bowel syndrome who do not respond to st and ard medical treatment Background Irritable bowel syndrome ( IBS ) is a functional disorder of the lower gastrointestinal ( GI ) tract affected by stress , which may benefit from a biopsychosocial treatment approach such as mindfulness-based stress reduction ( MBSR ) . Purpose A treatment as usual ( TAU ) wait-list controlled trial was conducted in Calgary , Canada to investigate the impact of MBSR on IBS symptoms . It was hypothesized that MBSR patients would experience greater reduction in overall IBS symptom severity and self-reported symptoms of stress relative to control patients . Method Ninety patients diagnosed with IBS using the Rome III criteria were r and omized to either an immediate MBSR program ( n = 43 ) or to wait for the next available program ( n = 47 ) . Patients completed IBS symptom severity , stress , mood , quality of life ( QOL ) , and spirituality scales pre- and post-intervention or waiting period and at 6-month follow-up . Intent-to-treat linear mixed model analyses for repeated measures were conducted , followed by completers analyses . Results While both groups exhibited a decrease in IBS symptom severity scores over time , the improvement in the MBSR group was greater than the controls and was clinical ly meaningful , with symptom severity decreasing from constantly to occasionally present . Pre- to post-intervention dropout rates of 44 and 23 % for the MBSR and control groups , respectively , Output:	However , across approaches , short-term benefits were seen . IBS symptoms improved significantly among patients in cognitive and behavioral therapies , mindfulness-based stress reduction , guided affective imagery , and emotional awareness training compared with controls ; there was a similar trend for gut-directed hypnotherapy .
MS2765	*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: PHY906 is a Chinese medicine formula with cl aims for the treatment of severe gastrointestinal distress . PHY906 enhanced the therapeutic index of various chemotherapeutic agents in human hepatocellular carcinoma xenografts . Accordingly , here a phase I/II clinical study was conducted with the combination of capecitabine in patients with advanced , unresectable hepatocellular carcinoma . More than 60 % of patients had either stable disease or better after two treatment cycles . Median overall survival was 9.2 months . Asian patients had a higher median overall survival ( 16.5 months ) than non-Asian patients ( 6.2 months , p=0.03 ) . Patients ' quality of life did not deteriorate significantly during treatment . This finding supported further investigation of PHY906 as an adjuvant therapy of capecitabine in a larger hepatocellular cancer population OBJECTIVE To observe the clinical effect of cinobufacini injection in treating moderate and advanced primary liver cancer ( PLC ) . METHODS One hundred patients with moderate and advanced PLC were r and omly divided into cino-treated group ( 50 patients ) and control group ( 50 patients ) . The quality of life , tumor size , some changes of laboratory tests , and survival time were observed . RESULTS The progressive rate of cino-treated group ( 18 % ) was lower than that of the control group ( 32 % ) . The quality of life of the cino-treated group ( 80 % ) was better than that of the control group ( 72 % ) , but without statistical significance . The survival rate of > 12 months of the cino-treated group ( 30 % ) was higher than that of the control group ( 18 % ) . The patients ' liver function such as serum total bilirubin and ALT decreased obviously in the cino-treated group while increased a lot in the control group . The level of AFP increased after treatment with statistical significance in the control group while there was no statistical significance in the cino-treated group . CONCLUSION Cinobufacini injection can not only inhibit the proliferation of cancer , but also protect liver function , improve quality of life and prolong survival time AIM To investigate anti-tumor activities and apoptosis-regulated mechanisms of bufalin in the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice . METHODS BEL-7402 cells of human hepatocellular carcinoma were inoculated to form subcutaneous tumors , and were implanted into the liver to establish orthotopic transplantation tumor models of human hepatocellular carcinoma in nude mice . Seventy-five animals were r and omized divided into five groups ( n = 15 ) . Bufalin was injected intraperitoneally into three groups at doses of 1.5 mg/kg ( BF1 ) , 1 mg/kg ( BF2 ) and 0.5 mg/kg ( BF3 ) for d 15 - 24 , respectively . The NS group was injected an equal volume of saline as above and adriamycin was injected intraperitoneally into the ADM group at a dose of 8.0 mg/kg for d 15 . Ten mice in each group were killed at d 25 and the survival time in each group was calculated . We also observed the morphologic alterations in the myocardium , brain , liver , kidney and tumor tissues by pathology and electron microscopy , measured the apoptotic rate by TUNEL staining method , and detected the expression of apoptosis-regulated genes bcl-2 and bax by immunohistochemical staining and RT-PCR in tumor tissues . RESULTS The tumor volumes in each group of bufalin were reduced significantly ( 35.21 + /- 12.51 vs 170.39 + /- 25.29 ; 49.83 + /- 11.46 vs 170.39 + /- 25.29 ; 83.99 + /- 24.63 vs 170.39 + /- 25.29 , P < 0.01 , respectively ) , and the survival times were prolonged in group BF1 - 2 ( 31.8 + /- 4.2 vs 23.4 + /- 2.1 and 29.4 + /- 3.4 vs 23.4 + /- 2.1 , P < 0.05 , respectively ) , and necrosis was mainly in severe or moderate degree in group BF1 - 2 . No morphological changes were detected in the myocardium , brain , liver and kidney tissues . Apoptotic characteristics could be seen in group BF1 - 2 . The positive rates of bcl-2 and bax protein expression of each group by immunohistochemical staining were 10.0 % , 10.0 % , 20.0 % , 10.0 % and 20.0 % ; 90.0 % , 80.0 % , 80.0 % , 40.0 % and 30.0 % , respectively . Loss of expression of bcl-2 mRNA in each group was to be found and the density of bax mRNA was increased progressively with increase of dose of bufalin by RT-PCR . CONCLUSION Bufalin has significant anti-tumor activities in the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice with no marked toxicity and was able to induce apoptosis of transplanted tumor cells . This apoptosis may be mediated mainly via up-regulating the expression of apoptosis-regulated gene bax , which may be involved in its anti-tumor mechanism of bufalin Purpose To study a commonly used Astragalus-based herbal formula previously found effective in non-small cell lung cancer ( NSCLC ) on the pharmacokinetics of docetaxel in patients with NSCLC . Methods Patients with advanced NSCLC who progressed after prior platinum-containing chemotherapy were accrued and received docetaxel at 35 mg/m2 for 3 weeks followed by 1 week of rest . At 4 days prior to the second dosing , Jinfukang was given orally . Pharmacokinetic studies of initial-dose docetaxel ( in the absence of Jinfukang ) and the third dose ( in the presence of Jinfukang ) were compared . Results Of the 24 patients enrolled , 21 started Jinfukang and docetaxel . Jinfukang had no significant impact on the pharmacokinetics of docetaxel . Median time to progression or withdrawal from treatment was 7 weeks . Twelve patients were removed from study for progression of disease ; nine patients withdrew . Conclusions Jinfukang did not alter the pharmacokinetics of docetaxel nor appear to affect survival in this study Huachansu , a Chinese medicine that comes from dried toad venom from the skin gl and s of Bufo gargarizans or B. melanostictus , has been used in the treatment of various cancers in China . The authors conducted a pilot study , using a phase 1 trial design , of huachansu in patients with advanced cancer Output:	The underst and ing of TCM Syndrome Differentiation may allow identification of different patterns of disharmony and may provide important guidance to the prescription of CHM .
MS2766	*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 Nocturnal gastroesophageal reflux ( nGER ) is common in patients with obstructive sleep apnea ( OSA ) . Small , short-term studies have shown that treatment with nasal continuous positive airway pressure ( CPAP ) decreases esophageal acid exposure . OBJECTIVE To examine the relationship between OSA and nGER , and the effect of CPAP on nGER , in a long-term follow-up study of a large cohort of patients with OSA and nGER . METHODS We prospect ively studied 331 patients diagnosed as having OSA between October 1 , 1993 , and November 30 , 2000 . At baseline , patients grade d their frequency of nGER symptoms on a scale of 1 ( never ) to 5 ( always ) . All patients were prescribed CPAP for their OSA . At follow-up , the frequency of nGER symptoms was obtained by telephone interview . RESULTS Of the 331 patients with OSA , nGER was present in 204 ( 62 % ) before treatment with CPAP . Follow-up was obtained in 181 patients ( 89 % ) . Of these 181 patients , 165 ( 91 % ) were still using CPAP and 16 ( 9 % ) were not , forming the treatment and control groups , respectively . The patients compliant with CPAP had a significant improvement in nGER score , from a mean of 3.38 before CPAP treatment to 1.75 after treatment ( 48 % improvement ; P<.001 ) , while patients not using CPAP ( control subjects ) showed no improvement ( mean , 3.56 to 3.44 ; P = .55 ) . There was a strong correlation between CPAP pressure and improvement in nGER score ( correlation , r = 0.70 ; P<.001 ) , with patients with higher CPAP pressures demonstrating a greater improvement in nGER score . CONCLUSIONS Nocturnal GER is common in patients with OSA . Treatment with nasal CPAP decreases the frequency of nGER symptoms by 48 % . Higher nasal CPAP pressures are associated with greater improvement in nGER OBJECTIVES : Sleep disturbances are common in patients with gastroesophageal reflux disease ( GERD ) . This study examined the effects of esomeprazole on nighttime heartburn , GERD-related sleep disturbances , sleep quality , work productivity , and regular activities . METHODS : This multicenter , r and omized , double-blind , placebo-controlled trial included adults with GERD-associated sleep disturbances and moderate-to-severe nighttime heartburn ( recorded by patient diary during screening ) . Patients received oral esomeprazole 40 mg ( n = 220 ) or 20 mg ( n = 226 ) or placebo ( n = 229 ) once daily for 4 wk . The primary outcome was relief of nighttime heartburn . Secondary outcomes included resolution of sleep disturbances , sleep quality measured by the Pittsburgh Sleep Quality Index ( PSQI ) question naire , and work productivity measured by the Work Productivity and Activity Impairment Question naire . RESULTS : Nighttime heartburn was relieved in 53.1 % ( 111/209 ) , 50.5 % ( 111/220 ) , and 12.7 % ( 28/221 ) of patients who received esomeprazole 40 mg , esomeprazole 20 mg , and placebo , respectively . Differences ( 95 % CI ) versus placebo were 40.5 % ( 32.4 % , 48.5 % ) and 37.8 % ( 29.9 % , 45.7 % ) and were highly significant ( p < 0.0001 ) . GERD-related sleep disturbances resolved in significantly more ( p < 0.0001 ) patients who received esomeprazole 40 ( 73.7 % ) or 20 mg ( 73.2 % ) than in those who received placebo ( 41.2 % ) . Both esomeprazole groups had greater PSQI global score changes from baseline ( p < 0.0001 vs placebo ) and more ( p < 0.0001 vs placebo ) work hours saved per week per patient compared with baseline ( esomeprazole 40 mg , 11.6 h ; esomeprazole 20 mg , 12.3 h ; placebo , 6.2 h ) . CONCLUSIONS : Esomeprazole reduced nighttime heartburn and GERD-related sleep disturbances and improved sleep quality and work productivity Nocturnal gastro-oesophageal reflux has been observed in patients with obstructive sleep apnoea ( OSA ) . Negative intrathoracic pressure during apnoeas and arousal have been suggested as the underlying mechanisms . In order to evaluate this hypothesis , the coincidence and sequence in time of arousal , apnoea and reflux events were analysed . Fifteen patients with OSA or heavy snoring were studied by means of st and ard polysomnograpy with parallel recording of 24-h oesophageal pH. Reflux events during the day were present in all patients , five of whom had symptoms of reflux . In three of these and in five other patients , a total of 69 nocturnal reflux events were found . In 68 events , arousal was found with the reflux event . Only one reflux without arousal was found ( sleep stage 2 ) . Seventeen events occurred during wakefulness after sleep onset . The percentage of time with a pH of < 4 during wakefulness after sleep onset was significantly higher than the percentage of time with a pH of < 4 during total sleep time ( p<0.05 ) . In 37 of the 52 reflux events which occurred during sleep , either an apnoea or a hypopnoea was found prior to the event . The investigation of sequence in time did not prove a causal relation between respiratory events and reflux events . The results indicate that gastro-oesophageal reflux and obstructive sleep apnoea are two separate disorders , which both have a high prevalence in obese patients STUDY OBJECTIVE To estimate the possible association between reported symptoms of gastroesophageal reflux ( GER ) after bedtime , sleep-disordered breathing , respiratory symptoms , and asthma . DESIGN Cross-sectional international population survey . PARTICIPANTS Participants consisted of 2,661 subjects ( age range , 20 to 48 years ) from three countries ( Icel and , Belgium , and Sweden ) , of whom 2,202 were r and omly selected from the general population and 459 were added because of reported asthma . MEASUREMENTS The investigation included a structured interview , spirometry , methacholine challenge , peak flow diary , skin-prick tests , and a question naire on sleep disturbances . RESULTS In the r and om population sample , 101 subjects ( 4.6 % ) reported GER , which was defined as the occurrence of heartburn or belching after going to bed at least once per week . Subjects with nocturnal GER more often were overweight and had symptoms of sleep-disordered breathing than participants not reporting GER . Participants with GER were more likely to report wheezing ( adjusted odds ratio [ OR ] , 2.5 ) , breathlessness at rest ( adjusted OR , 2.8 ) , and nocturnal breathlessness ( adjusted OR , 2.9 ) , and they had increased peak flow variability compared to the subjects without GER . Physician-diagnosed current asthma was reported by 9 % of subjects with GER compared to 4 % of those not reporting GER ( p < 0.05 ) . Subjects with the combination of asthma and GER had a higher prevalence of nocturnal cough , morning phlegm , sleep-related symptoms , and higher peak flow variability than subjects with asthma alone . CONCLUSION The occurrence of GER after bedtime is strongly associated with both asthma and respiratory symptoms , as well as symptoms of obstructive sleep apnea syndrome . The partial narrowing or occlusion of the upper airway during sleep , followed by an increase in intrathoracic pressure , might predispose the patient to nocturnal GER and , consequently , to respiratory symptoms OBJECTIVE : To determine the efficacy of pantoprazole therapy for daytime somnolence , psychomotor vigilance , and quality of life in patients with mild-moderate obstructive sleep disordered breathing ( OSDB ) and gastroesophageal reflux disease ( GERD ) . STUDY DESIGN : R and omized , double-blind , placebo-controlled crossover trial . METHODS : Sixty patients with daytime sleepiness , mildmoderate OSDB and GERD were r and omly assigned a 2-week treatment with pantoprazole 40 mg or placebo followed by a 2-week washout period and crossover respectively to 2-week treatment with placebo or pantoprazole . Outcomes included Epworth Sleepiness Score ( ESS ) , sleep-related quality -of-life ( FOSQ ) , and reaction time . RESULTS : With pantoprazole , patients reported statistically significantly greater improvement of overall reflux symptoms ( P = 0.0003 ) and in ESS ( P = 0.04 ) . A significant improvement was noted in FOSQ for both treatments with a trend toward greater improvement with pantoprazole ( P = 0.058 ) . No improvement in reaction times was observed . CONCLUSION : Patients with coexistent GERD and OSDB noted significant improvement in daytime sleepiness after treatment with pantoprazole over placebo likely related to a reduction in nocturnal reflux-related arousals OBJECTIVES To study the geographical variation in daytime sleepiness , snoring and disrupted breathing during sleep and to identify and compare risk factors using the same method in four European cities . DESIGN A cross-sectional , multicentre epidemiological survey . SETTING Reykjavik in Icel and , Uppsala and Göteborg in Sweden and Antwerp in Belgium . PARTICIPANTS A r and om population sample of 2202 subjects who participated in the European Community Respiratory Health Survey . MAIN OUTCOME MEASURES Sleep disturbances and daytime symptoms . RESULTS At all the centres , 5 % of the men and 2 - 3 % of the women reported snoring every night . Daytime sleepiness ( DS ) was more often reported in Uppsala [ odds ratio ( OR ) and 95 % confidence interval : 1.6 ( 1.2 - 2.1 ) ] than in the other centres , whilst daytime tiredness ( DT ) was most common in Reykjavik [ OR 1.8 ( 1.4 - 2.1 ) ] . Snoring was positively correlated with age , male gender and body-mass index in all areas . Symptoms of gastro-oesophageal reflux were associated with DS : OR 2.6 ( 1.5 4.4 ) and DT : OR 4.5 ( 2.7 - 7.6 ) and disrupted breathing : OR 3.8 ( 1.4 - 10 ) . DS and DT were reported more often by women than by men . CONCLUSION The prevalence of snoring was about the same in all four areas , whilst there was a geographical variation in daytime sleepiness and tiredness . As complaints of DS and DT and disrupted breathing were more common in subjects who reported symptoms of gastro-oesophageal reflux , we suggest that polysomnographic studies comparing sleep patterns in adult patients with and without reflux should be conducted OBJECTIVES : Nocturnal heartburn and related sleep disturbances are common among patients with gastroesophageal reflux disease ( GERD ) . This study evaluated the efficacy of dexlansoprazole MR 30 mg in relieving nocturnal heartburn and GERD-related sleep disturbances , improving work productivity , and decreasing nocturnal symptom severity in patients with symptomatic GERD . METHODS : Patients ( N=305 ) with frequent , moderate-to-very severe nocturnal heartburn and associated sleep disturbances were r and omized 1:1 in a double-blind fashion to receive dexlansoprazole MR or placebo once daily for 4 weeks . The primary end point was the percentage of nights without heartburn . Secondary end points were the percentage of patients with relief of nocturnal heartburn and of GERD-related sleep disturbances over the last 7 days of treatment . At baseline and week 4/final visit , patients completed question naires that assessed sleep quality , work productivity , and the severity and impact of nocturnal GERD symptoms . RESULTS : Dexlansoprazole MR 30 mg ( n=152 ) was superior to placebo ( n=153 ) in median percentage of nights without heartburn ( 73.1 vs. 35.7 % , respectively ; P<0.001 ) . Dexlansoprazole MR was significantly better than placebo in percentage of patients with relief of nocturnal heartburn and GERD-related sleep disturbances ( 47.5 vs. 19.6 % , 69.7 vs. 47.9 % , respectively ; P<0.001 ) , and led to significantly greater improvements in sleep quality and work productivity and decreased nocturnal symptom severity . Adverse events were similar across treatment groups . CONCLUSIONS : In patients with symptomatic GERD , dexlansoprazole MR 30 mg is significantly more efficacious than placebo in providing relief from nocturnal heartburn , in reducing GERD-related sleep disturbances and the consequent impairments in work productivity , and in improving sleep quality / quality of life BACKGROUND During sleep , individuals are uniquely vulnerable to acid reflux . Acid reflux during sleep has been studied by a number of investigators , but non-acid refl Output:	The existing evidence supports the use of proton pump inhibitors as a treatment for esophageal reflux disease to improve quality -of-life sleep disturbance – related outcomes .
MS2767	*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 Mild cognitive impairment ( MCI ) is a condition characterized by memory problems that are more severe than the normal cognitive changes due to aging , but less severe than dementia . Reduced working memory ( WM ) is regarded as one of the core symptoms of an MCI condition . Recent studies have indicated that WM can be improved through computer-based training . The objective of this study is to evaluate if WM training is effective in improving cognitive function in elderly patients with MCI , and if cognitive training induces structural changes in the white and gray matter of the brain , as assessed by structural MRI . Methods / Design sThe proposed study is a blinded , r and omized , controlled trail that will include 90 elderly patients diagnosed with MCI at a hospital-based memory clinic . The participants will be r and omized to either a training program or a placebo version of the program . The intervention is computerized WM training performed for 45 minutes of 25 sessions over 5 weeks . The placebo version is identical in duration but is non-adaptive in the difficulty level of the tasks . Neuropsychological assessment and structural MRI will be performed before and 1 month after training , and at a 5-month folllow-up . Discussion If computer-based training results in positive changes to memory functions in patients with MCI this may represent a new , cost-effective treatment for MCI . Secondly , evaluation of any training-induced structural changes to gray or white matter will improve the current underst and ing of the mechanisms behind effective cognitive interventions in patients with MCI.Trial registration Clinical Trials.gov NCT01991405 . November 18 , 2013 Background and Purpose — MRI is more sensitive than CT for detection of age-related white matter changes ( ARWMC ) . Most rating scales estimate the degree and distribution of ARWMC either on CT or on MRI , and they differ in many aspects . This makes it difficult to compare CT and MRI studies . To be able to study the evolution and possible effect of drug treatment on ARWMC in large patient sample s , it is necessary to have a rating scale constructed for both MRI and CT . We have developed and evaluated a new scale and studied ARWMC in a large number of patients examined with both MRI and CT . Methods — Seventy-seven patients with ARWMC on either CT or MRI were recruited and a complementary examination ( MRI or CT ) performed . The patients came from 4 centers in Europe , and the scans were rated by 4 raters on 1 occasion with the new ARWMC rating scale . The interrater reliability was evaluated by using & kgr ; statistics . The degree and distribution of ARWMC in CT and MRI scans were compared in different brain areas . Results — Interrater reliability was good for MRI ( & kgr;=0.67 ) and moderate for CT ( & kgr;=0.48 ) . MRI was superior in detection of small ARWMC , whereas larger lesions were detected equally well with both CT and MRI . In the parieto-occipital and infratentorial areas , MRI detected significantly more ARWMC than did CT . In the frontal area and basal ganglia , no differences between modalities were found . When a fluid-attenuated inversion recovery sequence was used , MRI detected significantly more lesions than CT in frontal and parieto-occipital areas . No differences were found in basal ganglia and infratentorial areas . Conclusions — We present a new ARWMC scale applicable to both CT and MRI that has almost equal sensitivity , except for certain regions . The interrater reliability was slightly better for MRI , as was the detectability of small lesions Background Older adults free of dementia but with subjective memory complaints ( SMC ) or mild cognitive impairment ( MCI ) are considered at increased risk of cognitive decline . Vascular risk factors ( VRF ) , including hypertension , heart disease , smoking , hypercholesterolemia and lack of physical activity ( PA ) have been identified as modifiable risk factors contributing to cognitive decline , and white matter hyperintensities ( WMH ) are associated with VRF , SMC and cognitive impairment . Findings from a growing number of clinical trials with older adults are providing strong evidence for the benefits of physical activity for maintaining cognitive function , but few studies are investigating these benefits in high-risk population s. The aim of AIBL Active is to determine whether a 24-month physical activity program can delay the progression of white matter changes on magnetic resonance imaging ( MRI ) . Methods / design This single-blind r and omized controlled trial ( RCT ) is offered to 156 participants , aged 60 and older , in the Melbourne arm of the Australian Imaging Biomarkers and Lifestyle Flagship Study of Aging ( AIBL ) . Participants must have SMC with or without MCI and at least one VRF . The PA intervention is a modification of the intervention previously trialed in older adults with SMC and MCI ( Fitness for the Ageing Brain Study ) . It comprises 24 months of moderate , home-based PA ( 150 minutes per week ) and a behavioral intervention package . The primary outcome measure will be change in WMH after 24 months on MRI . Cognition , quality of life , functional fitness , level of physical activity , plasma biomarkers for cerebrovascular disease and amyloid positron emission tomography ( PET ) imaging comprise secondary measures . Discussion Currently , there is no effective pharmacological treatment available to delay cognitive decline and dementia in older adults at risk . Should our findings show that physical activity can slow down the progression of WMH , this RCT would provide an important proof of concept . Since imbedded in AIBL this RCT will also be able to investigate the interaction between vascular and Alzheimer 's disease pathologies . Trial Registration Australia New Zeal and Clinical Trials Registry A growing body of research indicates benefits of cognitive training in older adults , but the neuronal mechanisms underlying the effect of cognitive intervention remains largely unexplored . Neuroimaging methods are sensitive to subtle changes in brain structure and show potential for enhancing our underst and ing of both aging- and training-related neuronal plasticity . Specifically , studies using diffusion tensor imaging ( DTI ) suggest substantial changes in white matter ( WM ) in aging , but it is not known whether cognitive training might modulate these structural alterations . We used tract-based spatial statistics ( TBSS ) optimized for longitudinal analysis to delineate the effects of 8 weeks intensive memory training on WM microstructure . 41 participants ( mean age 61 years ) matched for age , sex and education were r and omly assigned to an intervention or control group . All participants underwent MRI-scanning and neuropsychological assessment s at the beginning and end of the study . Longitudinal analysis across groups revealed significant increase in frontal mean diffusivity ( MD ) , indicating that DTI is sensitive to WM structural alterations over a 10-week interval . Further , group analysis demonstrated positive effects of training on the short-term changes . Participants in the training group showed a relative increase in fractional anisotropy ( FA ) compared with controls . Further , a significant relationship between memory improvement and change in FA was found , suggesting a possible functional significance of the reported changes . The training effect on FA seemed to be driven by a relative decrease in radial diffusivity , which might indicate a role for myelin-related processes in WM plasticity Abstract Non-demented community-dwelling older adults aged 70–90 years ( n = 1,037 ) r and omly recruited from the electoral roll completed neuropsychological and medical assessment s over six years . The overall prevalence of mild cognitive impairment ( MCI ) at baseline was 36.7 % . Risk factors for MCI include APOE ϵ4 allele carrier status , high homocysteine , heart disease , poor odour identification , low visual acuity and low mental activity , but notable age and sex differences were observed . Neuropsychiatric symptoms were rare ; depression was the most common and was associated with cognitive impairment in at least one domain as well as subsequent dementia 2 years later . Poorer cognitively dem and ing functional abilities were associated with cognitive impairment . Biomarkers for cognitive impairment and decline were identified . Inflammatory markers and plasma apolipoprotein levels were associated with poorer performance in the attention/processing speed domain . Measures of white matter lesions , white matter integrity , sulcal morphology and tractography were identified as novel biomarkers of early cognitive decline . Stronger deactivation in the posteromedial cortex with increasing memory load on functional MRI predicted future decline . Compared to previous reports , our prevalence rates of MCI were higher but rates of progression to dementia and reversion to normal were similar , as were risk factors for progression to dementia Output:	RESULTS Our review shows that 1 ) WM abnormality was identified between different subtypes of MCI and healthy controls on diffusion imaging ; 2 ) neither visual ratings of WML nor its volumetry differentiate different subtypes of MCI or its prognosis to dementia ; and 3 ) cognitive correlates of WML were evident in the Amnestic-type MCI in the domains of memory , language , psychomotor speed , attention and executive functions . CONCLUSION Cognitive reserve and the plasticity of white matter may modulate the impact of WML on the manifestation of the neurodegenerative disease .
MS2768	*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 the fields of both nursing and medicine there is a dearth of published literature on the optimum time to remove indwelling urinary catheters ( IDCs ) following urological surgery . Tradition seems to be in favour of removing IDCs at 0600 hours despite a lack of evidence to support this practice . This study was undertaken to determine whether midnight removal of IDCs result ed in patients ' resuming normal voiding patterns . A prospect i ve clinical trial was conducted to determine the impact midnight removal of urinary catheters would have on the patients ' voiding pattern , and subsequent discharge from hospital . One hundred and sixty patients were entered into the study . The patients were allocated at r and om to have their urinary catheter removed either at midnight or at 0600 hours . Patients who had their catheters removed at midnight passed a greater volume of urine with both their first ( 268 ml compared with 177 ml ; P<0.0001 ) and second voids ( 322 ml compared with 195 ml ; P<0.0001 ) than their counterparts in the 0600 group . This permitted earlier discharge from hospital . The results reported in this study support the findings of earlier research that midnight removal of IDC leads to an earlier resumption of normal voiding patterns , permits earlier discharge from hospital and appears to reduce patients ' anxiety . The recommendation from this study is that there should be a change in hospital policy so that the majority of IDCs are removed at midnight Patients who had undergone bladder neck surgery were r and omized to having their urethral catheters removed either early in the morning or late at night . There was no difference in the incidence of urinary retention between these two groups of patients . However , patients who presented with acute urinary retention had a higher incidence of postoperative urinary retention . This study suggests that a urethral catheter may be safely removed in the evening without increasing the risk of urinary retention . There also seems to be no greater chance of the patient having to be recatheterized at an unsocial hour PURPOSE This article describes a study that compares the outcomes of midnight versus early morning urethral catheter removal after transurethral resection of the prostate . SUBJECTS AND SETTING / METHODS : The research setting was a large , metropolitan hospital in Sydney , Australia . Forty-eight patients who had undergone transurethral resection of the prostate were r and omly assigned to either group A , catheter removal at 2400 hours ( n = 20 ) , or group B , catheter removal at 0600 hours ( n = 28 ) . MAIN OUTCOME MEASURES Data collected included time to first void , volume of first void , time between catheter removal and discharge from hospital , weight of prostatic resection , and tissue pathology . RESULTS There was no significant difference between the 2 groups with respect to pathology , weight of prostatic resection , mean volume of first void , or time to first void after catheter removal . There was a significant difference in the time between catheter removal and discharge from hospital . Eighty-five percent of those having catheters removed at 2400 hours were discharged on the same day as catheter removal , as compared with 65 % of those who underwent catheter removal at 0600 hours ( chi 2 = 12.684 ; P < 0.005 ) . CONCLUSION After transurethral resection of the prostate , removal of the urethral catheter at 2400 hours reduced the length of hospital stay , but did not significantly affect the time to first void or the volume of the first void The interval before removal of the catheter used in prostatic transurethral surgery depends to a great extent on the surgeon , with a frequently empirical orientation . We conducted a prospect i ve , r and omized and controlled study of 213 patients who underwent transurethral surgery for benign prostatic hyperplasia . The catheter was removed systematic ally 24 hours after transurethral incision and 48 hours after transurethral resection of the prostate ( group 1 - 52 and 54 patients , respectively ) or the catheterization interval was determined by each surgeon in accordance with the usual criteria ( group 2 - 52 and 55 patients , respectively ) . No statistically significant differences were noted between these 2 groups in regard to complications . We conclude that systematic removal of the catheter at the aforementioned periods is cost-effective , safe and comfortable for the patient This study shows that removal of urinary catheters at midnight has several advantages over removal at 6 AM . The midnight group had a significantly greater initial voided volume and a longer time to first void than the equivalent 6 AM group . Advantages to midnight catheter removal also exist for nursing staff . Midnight tends to be less busy on the nursing unit compared with 6 AM , thus making it a preferable time for performance of routine tasks . Catheter removal at midnight also allows for convenient observation of patient voiding and assessment earlier in the day . This means that any necessary intervention can take place during working hours when more staff are on duty . There is also the potential for earlier discharge , with economic benefits related to shorter bed stay and more efficient discharge planning . We believe midnight catheter removal offers considerable benefits over the traditional 6 AM time on both general and urology units OBJECTIVE To compare three methods for a trial of micturition ( TOM ) ( the midnight removal of the catheter , dawn removal , and a new infusion method ) in a r and omized prospect i ve study . PATIENTS AND METHODS A total of 118 consecutive patients who had undergone transurethral resection of the prostate ( TURP ) or bladder neck incision ( BNI ) underwent TOM by one of the three methods . In the infusion method , the bladder was filled at a fast-drip rate via the catheter from a bag of normal saline connected by an intravenous supply set . The catheter was then removed , the patient voided and the volume was measured . From the volume of saline remaining , it was possible to calculate the residual volume in the patient . RESULTS The infusion TOM took a mean 13 h less than the other two methods , which were statistically indistinguishable . CONCLUSION The infusion TOM is safe and simple , is quick to carry out and can be performed at any time . It establishes the completeness of bladder emptying , which helps in the assessment of voiding A r and omised controlled trial was undertaken to determine the effects of midnight removal of urinary catheters on patients ' voiding patterns and subsequent discharge from hospital . Patients whose urinary catheters were removed at midnight showed a greater volume of initial void than those whose catheters were removed at the usual time of 0600 . Removal of urinary catheters routinely at midnight permits earlier assessment of patients ' voiding , which may allow for earlier discharge from hospital Output:	Based on the limited available evidence , this article suggests benefits in terms of patient outcomes and reduction in the length of hospitalization after midnight removal of the IUCs .
MS2769	*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 Abstract Objectives : To examine the cost of providing hospital at home in place of some forms of inpatient hospital care . Design : Cost minimisation study within a r and omised controlled trial . Setting : District general hospital and catchment area of neighbouring community trust . Subjects : Patients recovering from hip replacement ( n=86 ) , knee replacement ( n=86 ) , and hysterectomy ( n=238 ) ; elderly medical patients ( n=96 ) ; and patients with chronic obstructive airways disease ( n=32 ) . Interventions : Hospital at home or inpatient hospital care . Main outcome measures : Cost of hospital at home scheme to health service , to general practitioners , and to patients and their families compared with hospital care . Results : No difference was detected in total healthcare costs between hospital at home and hospital care for patients recovering from a hip or knee replacement , or elderly medical patients . Hospital at home significantly increased healthcare costs for patients recovering from a hysterectomy ( ratio of geometrical means 1.15 , 95 % confidence interval 1.04 to 1.29 , P=0.009 ) and for those with chronic obstructive airways disease ( Mann-Whitney U test , P=0.01 ) . Hospital at home significantly increased general practitioners ' costs for elderly medical patients ( Mann-Whitney U test , P<0.01 ) and for those with chronic obstructive airways disease ( P=0.02 ) . Patient and carer expenditure made up a small proportion of total costs . Conclusion : Hospital at home care did not reduce total healthcare costs for the conditions studied in this trial , and costs were significantly increased for patients recovering from a hysterectomy and those with chronic obstructive airways disease . There was some evidence that costs were shifted to primary care for elderly medical patients and those with chronic obstructive airways disease . Key messages Hospital at home schemes are a popular alternative to st and ard hospital care , but there is uncertainty about their cost effectiveness In our r and omised controlled trial we compared the cost of hospital at home care with that of inpatient hospital care for patients recovering from hip replacement , knee replacement , and hysterectomy ; elderly medical patients ; and those with chronic obstructive airways disease There were no major differences in health service costs between the two arms of the trial for patients recovering from hip or knee replacement and elderly medical patients Hospital at home care increased healthcare costs for patients recovering from hysterectomy and for those with chronic obstructive airways disease Hospital at home care result ed in some costs shifting to general practitioners for elderly medical patients and those with chronic obstructive airways 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 — This proof-of-concept trial investigated the effects of an 8-week program of caregiver-mediated exercises commenced in hospital combined with tele-rehabilitation services on patient self-reported mobility and caregiver burden . Methods — Sixty-three hospitalized stroke patients ( mean age 68.7 , 64 % female ) were r and omly allocated to an 8-week caregiver-mediated exercises program with e-health support or usual care . Primary outcome was the Stroke Impact Scale mobility domain . Secondary outcomes included length of stay , other Stroke Impact Scale domains , readmissions , motor impairment , strength , walking ability , balance , mobility , ( extended ) activities of daily living , psychosocial functioning , self-efficacy , quality of life , and fatigue . Additionally , caregiver ’s self-reported fatigue , symptoms of anxiety , self-efficacy , and strain were assessed . Assessment s were completed at baseline and at 8 and 12 weeks . Results — Intention-to-treat analysis showed no between-group difference in Stroke Impact Scale mobility ( P=0.6 ) ; however , carers reported less fatigue ( 4.6 , confidence interval [ CI ] 95 % 0.3–8.8 ; P=0.04 ) and higher self-efficacy ( −3.3 , CI 95 % −5.7 to −0.9 ; P=0.01 ) at week 12 . Per- protocol analysis , examining those who were discharged home with tele-rehabilitation demonstrated a trend toward improved mobility ( −9.8 , CI 95 % −20.1 to 0.4 ; P=0.06 ) , significantly improved extended activities of daily living scores at week 8 ( −3.6 , CI 95 % −6.3 to −0.8 ; P=0.01 ) and week 12 ( 3.0 , CI 95 % −5.8 to −0.3 ; P=0.03 ) , a 9-day shorter length of stay ( P=0.046 ) , and fewer readmissions over 12 months ( P<0.05 ) . Conclusions — Caregiver-mediated exercises supported by tele-rehabilitation show promise to augment intensity of practice , result ing in improved patient-extended activities of daily living , reduced length of stay with fewer readmissions post stroke , and reduced levels of caregiver fatigue with increased feelings of self-efficacy . The current findings justify a larger definite phase III r and omized controlled trial . Clinical Trial Registration — URL : http://www.anzctr.org.au . Unique identifier : ACTRN12613000779774 Background Development of longer term stroke rehabilitation services is limited by lack of evidence of effectiveness for specific interventions and service models . We describe the protocol for a multicentre r and omised controlled trial which is evaluating an extended stroke rehabilitation service . The extended service commences when routine ‘ organised stroke care ’ ( stroke unit and early supported discharge ( ESD ) ) ends . Methods / design This study is a multicentre r and omised controlled trial with health economic and process evaluations . It is set within NHS stroke services which provide ESD . Participants are adults who have experienced a new stroke ( and carer if appropriate ) , discharged from hospital under the care of an ESD team . The intervention group receives an extended stroke rehabilitation service provided for 18 months following completion of ESD . The extended rehabilitation service involves regular contact with a senior ESD team member who leads and coordinates further rehabilitation . Contact is usually by telephone . The control group receives usual stroke care post-ESD . Usual care may involve referral of patients to a range of rehabilitation services upon completion of ESD in accordance with local clinical practice . R and omisation is via a central independent web-based service . The primary outcome is extended activities of daily living ( Nottingham Extended Activities of Daily Living Scale ) at 24 months post-r and omisation . Secondary outcomes ( at 12 and 24 months post-r and omisation ) are health status , quality of life , mood and experience of services for patients , and quality of life , experience of services and carer stress for carers . Re source use and adverse events are also collected . Outcomes are undertaken by a blinded assessor . Implementation and delivery of the extended stroke rehabilitation service will also be described . Semi-structured interviews will be conducted with a sub sample of participants and staff to gain insight into perceptions and experiences of rehabilitation services delivered or received . Allowing for 25 % attrition , 510 participants are needed to provide 90 % power to detect a difference in mean Nottingham Extended Activities of Daily Living Scale score of 6 with a 5 % significance level . Discussion The provision of longer term support for stroke survivors is currently limited . The results from this trial will inform future stroke service planning and configuration . Trial registration This trial was registered with IS RCT N ( identifier : IS RCT N45203373 ) on 9 August 2012 Background and Purpose — Early supported discharge from a stroke unit reduces the length of hospital stay . Evidence of a benefit for the patients is still unknown . The aim of this trial was to evaluate the long-term effects of an extended stroke unit service ( ESUS ) , characterized by early supported discharge . The short-term effects were published previously . Methods — We performed a r and omized controlled trial in which 320 acute stroke patients were allocated to either ordinary stroke unit service ( OSUS ) ( 160 patients ) or stroke unit care with early supported discharge ( 160 patients ) . The ESUS consists of a mobile team that coordinates early supported discharge and further rehabilitation . Primary outcome was the proportion of patients who were independent as assessed by modified Rankin Scale ( RS ) ( RS ≤2=global independence ) . Secondary outcomes measured at 52 weeks were performance on the Barthel Index ( BI ) ( BI ≥95=independent in activities of daily living ) , differences in final residence , and analyses to identify patients who benefited most from an early supported discharge service . All assessment s were blinded . Results — We found that 56.3 % of the patients in the ESUS versus 45.0 % in the OSUS were independent ( RS ≤2 ) ( P = 0.045 ) . The number needed to treat to achieve 1 independent patient in ESUS versus OSUS was 9 . The odds ratio for independence was 1.56 ( 95 % CI , 1.01 to 2.44 ) . There were no significant differences in BI score and final residence . Patients with moderate to severe stroke benefited most from the ESUS . Conclusions — Stroke service based on treatment in a stroke unit combined with early supported discharge appears to improve the long-term clinical outcome compared with ordinary stroke unit care . Patients with moderate to severe stroke benefit most Background and Purpose — Early supported discharge ( ESD ) seems to be a promising alternative to conventional follow-up care after acute stroke . We have previously shown that stroke unit care combined with ESD has beneficial effects on functional outcome and the use of re sources for up to 1 year . The aim of this trial was to evaluate outcome after 5 years . Methods — We performed a r and omized controlled trial with 320 acute stroke patients allocated to ordinary stroke unit care ( 160 patients ) or stroke unit care with ESD ( 160 patients ) . The ESD service consisted of a mobile team that co-coordinated hospital discharge and further rehabilitation during 1 month of follow-up in cooperation with the primary health care . Mortality , residence , and functional outcome including modified Rankin scale were registered after 5 years . All assessment s were blinded . Results — There was no difference between the groups with modified Rankin scale score ⩽2 ( P=0.213 ) , but there was a trend toward greater improvement in modified Rankin scale score in the ESD group from onset of stroke ( 38 % versus 30 % ; P=0.106 ) . More patients were dead or institutionalized in the ordinary stroke unit care group ( P=0.032 ) ; 158 patients were alive , 84 were in ESD , and 74 were in ordinary stroke unit care . Of the 158 patients alive , a greater proportion were living at home in ESD ( 86%/70 % ; P=0.019 ) . Conclusions — Stroke unit care combined with ESD seems to reduce death and institutional care and to improve patients ' chances of living at home 5 years after stroke compared to traditional stroke care Output:	Participants tended to be a selected elderly group of stroke survivors with moderate disability . We saw no clear differences in participants ' activities of daily living scores , patients subjective health status or mood , or the subjective health status , mood or satisfaction with services of carers . Appropriately re source d ESD services with co-ordinated multidisciplinary team input provided for a selected group of stroke patients can reduce long-term dependency and admission to institutional care as well as reducing the length of hospital stay . Results are inconclusive for services without co-ordinated multidisciplinary team input . We observed no adverse impact on the mood or subjective health status of patients or carers , nor on readmission to hospital
MS2770	*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 Pharmacotherapies for smoking cessation have not been adequately tested in pregnancy and women are reluctant to use them . Behavioural support alone has a modest effect on cessation rates ; therefore , more effective interventions are needed . Even moderate intensity physical activity ( e.g. brisk walk ) reduces urges to smoke and there is some evidence it increases cessation rates in non-pregnant smokers . Two pilot studies assessed i ) the feasibility of recruiting pregnant women to a trial of physical activity for smoking cessation , ii ) adherence to physical activity and iii ) womens ' perceptions of the intervention . Methods Pregnant smokers volunteered for an intervention combining smoking cessation support , physical activity counselling and supervised exercise ( e.g. treadmill walking ) . The first study provided six weekly treatment sessions . The second study provided 15 sessions over eight weeks . Physical activity levels and continuous smoking abstinence ( verified by expired carbon monoxide ) were monitored up to eight months gestation . Results Overall , 11.6 % ( 32/277 ) of women recorded as smokers at their first antenatal booking visit were recruited . At eight months gestation 25 % ( 8/32 ) of the women achieved continuous smoking abstinence . Abstinent women attended at least 85 % of treatment sessions and 75 % ( 6/8 ) achieved the target level of 110 minutes/week of physical activity at end-of-treatment . Increased physical activity was maintained at eight months gestation only in the second study . Women reported that the intervention helped weight management , reduced cigarette cravings and increased confidence for quitting . Conclusion It is feasible to recruit pregnant smokers to a trial of physical activity for smoking cessation and this is likely to be popular . A large r and omised controlled trial is needed to examine the efficacy of this intervention Aerobic exercise can acutely reduce cigarette cravings during periods of nicotine deprivation . The primary aim of this study was to assess the differential effects of light and vigorous intensity aerobic exercise on cigarette cravings , subjective and physiological reactivity to smoking cues , and affect after overnight nicotine deprivation . A secondary aim was to examine cortisol change as a mediator of the effects of exercise on smoking motivation . 162 ( 55 female , 107 male ) overnight nicotine-deprived smokers were r and omized to one of three exercise conditions : light intensity , vigorous intensity , or a passive control condition . After each condition , participants engaged in a st and ardized cue reactivity assessment . Self-reported urges to smoke , affect , and salivary cortisol were assessed at baseline ( i.e. , before each condition ) , immediately after each condition , and after the cue reactivity assessment . Light and vigorous exercise significantly decreased urges to smoke and increased positive affect , relative to the control condition . In addition , those in the vigorous exercise condition demonstrated suppressed appetitive reactivity to smoking cues , as indexed by the startle eyeblink reflex . Although exercise intensity was associated with expected changes in cortisol concentration , these effects were not related to changes in craving or cue reactivity . Both light and vigorous exercise can reduce general cravings to smoke , whereas vigorous exercise appears especially well-suited for reducing appetitive reactions to cues that may precede smoking . Results did not support exercise-induced cortisol release as a mechanism for these effects Exercise has been hypothesized to curb increases in depressive symptoms often associated with smoking cessation . The relationship between increased fitness and changes in depressive symptoms was examined among 40 women who were abstinent at the end of an 8-week r and omized controlled trial . Participants received group-based , cognitive-behavioral smoking cessation treatment plus either exercise or contact control . All participants completed maximal fitness tests and question naires , including the Centers for Epidemiological Studies Depression Scale at baseline and at post-treatment . Regardless of treatment assignment , women who increased fitness over the 8-week treatment period were more likely to have decreases in depressive symptoms . Results indicate that increased fitness may benefit women by attenuating the depressive symptoms often associated with nicotine withdrawal INTRODUCTION AND OBJECTIVES To assess the efficacy of cardiac rehabilitation with a mixed primary and cardiological care program in patients with low-risk myocardial infa rct ion . PATIENTS AND METHOD The participants in this 12-month prospect i ve study were 153 consecutive patients with low-risk myocardial infa rct ion ( MI ) referred to their primary care center for follow-up care . Of these patients , 113 were referred to a mixed primary and specialized care program that included physical exercise , cardiovascular risk control , an antismoking program , health education talks and psychological evaluation . The other 40 patients served as controls . We analyzed the results after 3 months and 1 year of follow-up . RESULTS There were no differences between the two groups at baseline . After 1 year , improvements were seen in smoking habit ( 4.6 % vs 15.6 % ; P<.05 ) and body mass index ( 26 [ 2 ] vs 29 [ 2 ] ; P<.05 ) . Dyslipidemia , glucose and blood pressure were similar in both groups after follow-up . Greater improvements in the group of patients who participated in the program were seen after 1 year in quality of life ( 78 [ 2 ] vs 91 [ 2 ] ; P<.05 ) , exercise capacity ( 10.3 [ 2 ] vs 8.4 [ 3 ] ; P<<.01 ) and return to active employment ( 84.6 % vs 53.3 % ; P<.05 ) . CONCLUSIONS After 1 year of follow-up , the cardiac rehabilitation program coordinated by cardiological and primary care services for low-risk post-MI patients improved quality of life , and increased exercise tolerance , active employment , and the number of participants who quit smoking . The mixed program also reduced body mass index . These results suggest the need for similar programs Background Many women try to stop smoking in pregnancy but fail . One difficulty is that there is insufficient evidence that medications for smoking cessation are effective and safe in pregnancy and thus many women prefer to avoid these . Physical activity ( PA ) interventions may assist cessation ; however , trials examining these interventions have been too small to detect or exclude plausible beneficial effects . The London Exercise And Pregnant smokers ( LEAP ) trial is investigating whether a PA intervention is effective and cost-effective when used for smoking cessation by pregnant women , and will be the largest study of its kind to date . Methods / design The LEAP study is a pragmatic , multi-center , two-arm , r and omized , controlled trial that will target pregnant women who smoke at least one cigarette a day ( and at least five cigarettes a day before pregnancy ) , and are between 10 and 24 weeks pregnant . Eligible patients are individually r and omized to either usual care ( that is , behavioral support for smoking cessation ) or usual care plus a intervention ( entailing supervised exercise on a treadmill plus PA consultations ) . The primary outcome of the trial is self-reported and biochemically vali date d continuous abstinence from smoking between a specified quit date and the end of pregnancy . The secondary outcomes , measured at 1 and 4 weeks after the quit date , and at the end of pregnancy and 6 months after childbirth , are PA levels , depression , self-confidence , and cigarette withdrawal symptoms . Smoking status will also be self-reported at 6 months after childbirth . In addition , perinatal measures will be collected , including antenatal complications , duration of labor , mode of delivery , and birth and placental weight . Outcomes will be analyzed on an intention-to-treat basis , and logistic regression models used to compare treatment effects on the primary outcome . Discussion This trial will assess whether a PA intervention is effective when used for smoking cessation during pregnancy . Trial registration IS RCT This study examined the relationship between changes in physical activity and changes in smoking among adolescents . We prospect ively examined smoking progression , physical activity , demographic factors , and covariates in 978 high school students participating in a longitudinal cohort study of the predictors of smoking adoption . We used latent growth modeling with the parallel processes smoking progression and physical activity as our method , with smoking progression measured as an ordered categorical variable . Results indicated that higher levels of physical activity reduced the odds of progressing to smoking or a higher level of smoking by nearly 1.5 ( 1.44 ; P < 0.05 ) . No race differences were found . However , being male increased the odds of smoking progression by 1.32 ( P < 0.05 ) . Higher levels of physical activity may reduce the risk of smoking during adolescence . Youth smoking prevention initiatives should incorporate strategies to promote physical activity to prevent smoking experimentation and escalation Abstract The accurate assessment of both tobacco withdrawal and the impact of the nicotine patch on withdrawal may be compromised by attrition of subjects , or by subjects smoking during withdrawal . To reduce these occurrences , 211 participants were provided with intensive cessation counseling while trying to quit smoking with either nicotine ( 21 mg ) or placebo transdermal patches . Subject attrition was low , with 80.5 % of participants continuing through the 5-week study period . Abstinence rates were also high over this period ( 75 % and 61 % in active and placebo groups , respectively ) . In this multisite , double-blind trial , withdrawal severity was assessed using a nine-item daily self-report question naire , and abstinence was confirmed via CO monitoring . Abrupt smoking cessation increased multiple tobacco withdrawal symptoms/signs including craving for cigarettes , irritability , anxiety , appetite , sleep disruption , difficulty concentrating , restlessness , depression , and impatience . Treatment with transdermal nicotine reduced craving for cigarettes , anxiety , irritability , and appetite , as well as weight gain ( 1.85 versus 2.88 kg mean gain over 4 weeks in active and placebo groups , respectively ) Abstract Objective To compare the hazards of cigarette smoking in men who formed their habits at different periods , and the extent of the reduction in risk when cigarette smoking is stopped at different ages . Design Prospect i ve study that has continued from 1951 to 2001 . Setting United Kingdom . Participants 34 439 male British doctors . Information about their smoking habits was obtained in 1951 , and periodically thereafter ; cause specific mortality was monitored for 50 years . Main outcome measures Overall mortality by smoking habit , considering separately men born in different periods . Results The excess mortality associated with smoking chiefly involved vascular , neoplastic , and respiratory diseases that can be caused by smoking . Men born in 1900 - 1930 who smoked only cigarettes and continued smoking died on average about 10 years younger than lifelong non-smokers . Cessation at age 60 , 50 , 40 , or 30 years gained , respectively , about 3 , 6 , 9 , or 10 years of life expectancy . The excess mortality associated with cigarette smoking was less for men born in the 19th century and was greatest for men born in the 1920s . The cigarette smoker versus non-smoker probabilities of dying in middle age ( 35 - 69 ) were 42 % ν24 % ( a twofold death rate ratio ) for those born in 1900 - 1909 , but were 43 % ν 15 % ( a threefold death rate ratio ) for those born in the 1920s . At older ages , the cigarette smoker versus non-smoker probabilities of surviving from age 70 to 90 were 10 % ν 12 % at the death rates of the 1950s ( that is , among men born around the 1870s ) but were 7 % ν 33 % ( again a threefold death rate ratio ) at the death rates of the 1990s ( that is , among men born around the 1910s ) . Conclusion A substantial progressive decrease in the mortality rates among non-smokers over the past half century ( due to prevention and improved treatment of disease ) has been wholly outweighed , among cigarette smokers , by a progressive increase in the smoker ν non-smoker death rate ratio due to earlier and more intensive use of cigarettes . Among the men born around 1920 , prolonged cigarette smoking from early adult life tripled age specific mortality rates , but cessation at age 50 halved the hazard , and cessation at age 30 avoided almost all of it INTRODUCTION Quitting smoking is associated with weight gain , which may threaten motivation to engage or sustain a quit attempt . The pattern of weight gained by smokers treated according to smoking cessation guidelines has been poorly described . We aim ed to determine the weight gained after smoking cessation and its predictors , by smokers receiving individual counseling and nicotine replacement therapies for smoking cessation . METHODS We performed an ancillary analysis of a r and omized controlled trial assessing moderate physical activity as an aid for smoking cessation in addition to st and ard treatment in sedentary adult smokers . We used mixed longitudinal models to describe the evolution of weight over time , thus allowing us to take every participant into account . We also fitted a model to assess the effect of smoking status and reported use of nicotine replacement therapy at each time point . We adjusted for intervention group , sex , age , nicotine dependence , and education . RESULTS In the whole cohort , weight increased in the first 3 months , and stabilized afterwards . Mean 1-year weight gain was 3.3 kg for women and 3.9 kg for men ( p = .002 ) . Higher nicotine dependence and male sex were associated Output:	The other studies showed no significant effect for exercise on abstinence .
MS2771	*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 Enzalutamide ( formerly called MDV3100 ) targets multiple steps in the and rogen-receptor-signaling pathway , the major driver of prostate-cancer growth . We aim ed to evaluate whether enzalutamide prolongs survival in men with castration-resistant prostate cancer after chemotherapy . METHODS In our phase 3 , double-blind , placebo-controlled trial , we stratified 1199 men with castration-resistant prostate cancer after chemotherapy according to the Eastern Cooperative Oncology Group performance-status score and pain intensity . We r and omly assigned them , in a 2:1 ratio , to receive oral enzalutamide at a dose of 160 mg per day ( 800 patients ) or placebo ( 399 patients ) . The primary end point was overall survival . RESULTS The study was stopped after a planned interim analysis at the time of 520 deaths . The median overall survival was 18.4 months ( 95 % confidence interval [ CI ] , 17.3 to not yet reached ) in the enzalutamide group versus 13.6 months ( 95 % CI , 11.3 to 15.8 ) in the placebo group ( hazard ratio for death in the enzalutamide group , 0.63 ; 95 % CI , 0.53 to 0.75 ; P<0.001 ) . The superiority of enzalutamide over placebo was shown with respect to all secondary end points : the proportion of patients with a reduction in the prostate-specific antigen ( PSA ) level by 50 % or more ( 54 % vs. 2 % , P<0.001 ) , the soft-tissue response rate ( 29 % vs. 4 % , P<0.001 ) , the quality -of-life response rate ( 43 % vs. 18 % , P<0.001 ) , the time to PSA progression ( 8.3 vs. 3.0 months ; hazard ratio , 0.25 ; P<0.001 ) , radiographic progression-free survival ( 8.3 vs. 2.9 months ; hazard ratio , 0.40 ; P<0.001 ) , and the time to the first skeletal-related event ( 16.7 vs. 13.3 months ; hazard ratio , 0.69 ; P<0.001 ) . Rates of fatigue , diarrhea , and hot flashes were higher in the enzalutamide group . Seizures were reported in five patients ( 0.6 % ) receiving enzalutamide . CONCLUSIONS Enzalutamide significantly prolonged the survival of men with metastatic castration-resistant prostate cancer after chemotherapy . ( Funded by Medivation and Astellas Pharma Global Development ; AFFIRM Clinical Trials.gov number , NCT00974311 . ) Primary resistance to and rogen receptor (AR)-directed therapies in metastatic castration-resistant prostate cancer ( mCRPC ) is poorly understood . We r and omized 202 patients with treatment-naïve mCRPC to abiraterone or enzalutamide and performed whole-exome and deep targeted 72-gene sequencing of plasma cell-free DNA prior to therapy . For these agents , which have never been directly compared , time to progression was similar . Defects in BRCA2 and ATM were strongly associated with poor clinical outcomes independently of clinical prognostic factors and circulating tumor DNA abundance . Somatic alterations in TP53 , previously linked to reduced tumor dependency on AR signaling , were also independently associated with rapid resistance . Although detection of AR amplifications did not outperform st and ard prognostic biomarkers , AR gene structural rearrangements truncating the lig and binding domain were identified in several patients with primary resistance . These findings establish genomic drivers of resistance to first-line AR-directed therapy in mCRPC and identify potential minimally invasive biomarkers . Significance : Leveraging plasma specimens collected in a large r and omized phase II trial , we report the relative impact of common circulating tumor DNA alterations on patient response to the most widely used therapies for advanced prostate cancer . Our findings suggest that liquid biopsy analysis can guide the use of AR-targeted therapy in general practice . Cancer Discov ; 8(4 ) ; 444 - 57 . © 2018 AACR.See related commentary by Jayaram et al. , p. 392This article is highlighted in the In This Issue feature , p. 371 PURPOSE Persistent and rogen signaling is implicated in castrate-resistant prostate cancer ( CRPC ) progression . This study aim ed to evaluate and rogen signaling in bone marrow-infiltrating cancer and testosterone in blood and bone marrow and to correlate with clinical observations . PATIENTS AND METHODS This was an open-label , observational study of 57 patients with bone-metastatic CRPC who underwent transiliac bone marrow biopsy between October 2007 and March 2010 . Patients received oral abiraterone acetate ( 1 g ) once daily and prednisone ( 5 mg ) twice daily . And rogen receptor ( AR ) and CYP17 expression were assessed by immunohistochemistry , testosterone concentration by mass spectrometry , AR copy number by polymerase chain reaction , and TMPRSS2-ERG status by fluorescent in situ hybridization in available tissues . RESULTS Median overall survival was 555 days ( 95 % CI , 440 to 965 + days ) . Maximal prostate-specific antigen decline ≥ 50 % occurred in 28 ( 50 % ) of 56 patients . Homogeneous , intense nuclear expression of AR , combined with ≥ 10 % CYP17 tumor expression , was correlated with longer time to treatment discontinuation ( > 4 months ) in 25 patients with tumor-infiltrated bone marrow sample s. Pretreatment CYP17 tumor expression ≥ 10 % was correlated with increased bone marrow aspirate testosterone . Blood and bone marrow aspirate testosterone concentrations declined to less than picograms-per-milliliter levels and remained suppressed at progression . CONCLUSION The observed pretreatment and rogen-signaling signature is consistent with persistent and rogen signaling in CRPC bone metastases . This is the first evidence that abiraterone acetate achieves sustained suppression of testosterone in both blood and bone marrow aspirate to less than picograms-per-milliliter levels . Potential admixture of blood with bone marrow aspirate limits our ability to determine the origin of measured testosterone Output:	ABI-to-ENZ sequential therapy in patients with CRPC was associated with better PFS , PSA – PFS , and PSA response rates . Regardless of sequencing , response to drug therapy was transient for both ABI and ENZ when either agent was used as a secondary therapy .
MS2772	*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 prospect i ve r and omized study the efficiacy of physical therapy in female stress incontinence could be verified . The greatest success rate was achieved by medical gymnastics , whereas the perineal electrical stimulation should be used as supporting measure like a biofeedback mechanism because of its low effective intensity . Despite of the good therapeutic success ( 51.5 % ) with lasting effects no objective criteria to the use of physical therapy in female stress incontinence were found Fifty consecutive female patients with genuine urinary stress incontinence were r and omized either to surgery or to a pelvic floor training program . The operative procedure was chosen according to the type of bladder suspension defect on micturition cystourethrography . The training program was given 5 times in weekly lessons and the patients were guided by trained physiotherapists . Surgery was superior to the pelvic floor training program both subjectively and objective ly . However , a significant improvement was found following the training program . Forty-two percent were satisfied with the outcome of the training and did not want operation . We find physiotherapist-guided pelvic floor exercise a realistic alternative to surgery in patients with mild degrees of stress incontinence . Also patients with residual symptoms after surgery are c and i date s for pelvic floor training CONTEXT Urinary incontinence is a common condition caused by many factors with several treatment options . OBJECTIVE To compare the effectiveness of biofeedback-assisted behavioral treatment with drug treatment and a placebo control condition for the treatment of urge and mixed urinary incontinence in older community-dwelling women . DESIGN R and omized placebo-controlled trial conducted from 1989 to 1995 . SETTING University-based outpatient geriatric medicine clinic . PATIENTS A volunteer sample of 197 women aged 55 to 92 years with urge urinary incontinence or mixed incontinence with urge as the predominant pattern . Subjects had to have urodynamic evidence of bladder dysfunction , be ambulatory , and not have dementia . INTERVENTION Subjects were r and omized to 4 sessions ( 8 weeks ) of biofeedback-assisted behavioral treatment , drug treatment ( with oxybutynin chloride , possible range of doses , 2.5 mg daily to 5.0 mg 3 times daily ) , or a placebo control condition . MAIN OUTCOME MEASURES Reduction in the frequency of incontinent episodes as determined by bladder diaries , and patients ' perceptions of improvement and their comfort and satisfaction with treatment . RESULTS For all 3 treatment groups , reduction of incontinence was most pronounced early in treatment and progressed more gradually thereafter . Behavioral treatment , which yielded a mean 80.7 % reduction of incontinence episodes , was significantly more effective than drug treatment ( mean 68.5 % reduction ; P=.04 ) and both were more effective than the placebo control condition ( mean 39.4 % reduction ; P<.001 and P=.009 , respectively ) . Patient-perceived improvement was greatest for behavioral treatment ( 74.1 % " much better " vs 50.9 % and 26.9 % for drug treatment and placebo , respectively ) . Only 14.0 % of patients receiving behavioral treatment wanted to change to another treatment vs 75.5 % in each of the other groups . CONCLUSION Behavioral treatment is a safe and effective conservative intervention that should be made more readily available to patients as a first-line treatment for urge and mixed incontinence PURPOSE We determine the efficacy and user acceptability of the urethral occlusive device ( FemAssist ) for incontinence for 1 month and identify factors that may predict successful use of the device . MATERIAL S AND METHODS Baseline and posttreatment outcome measures included a 1-hour pad test , frequency volume chart ( leakage , voiding and number of pads per 24 hour ) , visual analog scale for incontinence impact and quality of life ( Urogenital Distress Inventory ) . The last 36 consecutive women also completed a linear analog scale about attitudes toward touching the genitalia . RESULTS The device was offered to 100 consecutive incontinent women of whom 3 did not enroll in the study and 57 ( 57 % ) completed the 1-month trial . Age , incontinence type or severity and attitudes about touching the genitalia were not significantly different between dropouts and participants . Only 13 % of recruits were disinclined to place the device on the urethra . Significant reduction of incontinence was observed for all outcome measures with the device in situ . Pad testing revealed that 47 % of the patients became continent and 33 % had more than 50 % benefit , while 9 % had worse leakage . Those with severe baseline leakage were equally likely to respond as those with mild or moderate pad test loss . Women with stress , urge or mixed incontinence appeared to respond equally well . CONCLUSIONS The urethral occlusive device provides a further nonsurgical treatment option which is useful for a range of incontinence types In the United Kingdom regular urinary incontinence affects over 2000000 women and costs the NHS about pounds sterling70 million a year on aids and appliances . The assessment and treatment services lack a coherent plan for its recognition and treatment , and where and from whom care is best received is debated.1 Few of the current management strategies ( pelvic exercises , appliances , drugs , and surgery ) have been the subject of well design ed r and omised controlled trials in primary care , and few studies have reported long term results .2 3 4 Thus lack of evidence combined with poorly trained primary care physicians and nurses has meant that fewer than one in three patients are recognised and fewer still are appropriately managed.1 In 1991 we reported the results Sixty-nine female patients with symptoms of stress urinary incontinence were r and omized to treatment with either interferential therapy or weighted vaginal cones . Fifty-four patients completed treatment ( interferential therapy , 30 patients ; weighted vaginal cones , 24 patients ) . Patients were assessed by subjective response , pad testing , continence charts , and the maximum weight of cone that could be held actively and passively . Forty-seven patients were reassessed at 6 months ( 19 cones ; 28 interferential ) , five patients ( 9.26 % ) required surgery , and two patients ( 3.7 % ) could not be reassessed . Subjective response to treatment was good , with 80 % to 90 % of patients cured or improved after treatment . After 6 months , 41.67 % in the cone group and 40 % in the interferential group were subjectively cured , with improvement in 50 % and 30 % , respectively . Of those patients initially referred for treatment , greater than 30 % in each group were cured of symptoms . There was an objective improvement in both groups . In the cone group 50 % had improved after treatment and greater than 60 % had improved at 6 months as assessed by pad testing , while in the interferential group 76 % had improved after treatment and 73 % had improved at 6 months . There was no significant difference in improvement between the two groups in any of the methods of assessment . However , the cones require less supervision by trained staff and can be used at home by the patient . Their use results in a savings in time for the physiotherapy department . The use of the cones is recommended as a cost-effective method of treatment that can be added to the present therapy options available to the physiotherapist The aim of this study was to assess the usefulness of pelvic floor exercises in the treatment of urinary incontinence in women and to analyse the factors which determine a successful outcome . The study involved 66 women who had reported ' genuine stress incontinence ' to their general practitioner . They were assigned at r and om to the treatment or control group . The treatment group received instructions in pelvic floor exercises from a general practitioner . The control group received no therapy . At the start of the trial the severity of the patients ' incontinence was assessed objective ly . This assessment was repeated after three months and patients were also asked for their own perception of whether their incontinence had improved . After the three months ' evaluation the patients in the control group were also given instructions in pelvic floor exercises . After another three months they were assessed in the same way . About 60 % of the patients in the treatment group were dry or mildly incontinent after three months compared with only one patient in the control group ; the mean weekly frequency of incontinence episodes fell from 17 to five in the treatment group but remained virtually unchanged in the control group ; and about 85 % of the women in the treatment group felt that their incontinence had improved or was cured compared with no one in the control group . These results were later corroborated by those for the control group . The most important factor in the success of the treatment was the patients ' motivation , as demonstrated by their adherence to the daily exercises . ( ABSTRACT TRUNCATED AT 250 WORDS Abstract Objective : To compare the effect of pelvic floor exercises , electrical stimulation , vaginal cones , and no treatment for genuine stress incontinence . Design : Stratified , single blind , r and omised controlled trial . Setting : Multicentre . Participants : 107 women with clinical ly and urodynamically proved genuine stress incontinence . Mean ( range ) age was 49.5 ( 24 - 70 ) years , and mean ( range ) duration of symptoms 10.8 ( 1 - 45 ) years . Interventions : Pelvic floor exercise ( n=25 ) comprised 8 - 12 contractions 3 times a day and exercise in groups with skilled physical therapists once a week . The electrical stimulation group ( n=25 ) used vaginal intermittent stimulation with the MS 106 Twin at 50 Hz 30 minutes a day . The vaginal cones group ( n=27 ) used cones for 20 minutes a day . The untreated control group ( n=30 ) was offered the use of a continence guard . Muscle strength was measured by vaginal squeeze pressure once a month . Main outcome measures : Pad test with st and ardised bladder volume , and self report of severity . Results : Improvement in muscle strength was significantly greater ( P=0.03 ) after pelvic floor exercises ( 11.0 cm H2O ( 95 % confidence interval 7.7 to 14.3 ) before v 19.2 cm H2O ( 15.3 to 23.1 ) after ) than either electrical stimulation ( 14.8 cm H2O ( 10.9 to 18.7 ) v 18.6 cm H2O ( 13.3 to 23.9 ) ) or vaginal cones ( 11.8 cm H2O ( 8.5 to 15.1 ) v 15.4 cm H2O ( 11.1 to 19.7 ) ) . Reduction in leakage on pad test was greater in the exercise group ( −30.2 g ; −43.3 to 16.9 ) than in the electrical stimulation group ( −7.4 g ; −20.9 to 6.1 ) and the vaginal cones group ( −14.7 g ; −27.6 to −1.8 ) . On completion of the trial one participant in the control group , 14 in the pelvic floor exercise group , three in the electrical stimulation group , and two in the vaginal cones group no longer considered themselves as having a problem . Conclusion : Training of the pelvic floor muscles is superior to electrical stimulation and vaginal cones in the treatment of genuine stress incontinence OBJECTIVE --To measure the unmet need of patients with regular urinary incontinence ( incontinence twice or more a month ) treatable by a nurse . DESIGN --Self completed postal question naire and r and omised controlled trial of assessment and intervention by a nurse . SETTING --One urban and one rural general practice in Somerset . SUBJECTS--7300 adults r and omly selected from 10,300 aged 35 and over on the combined practice lists . 515 women and 185 men with regular incontinence were offered assessment and treatment , of whom 134 women and 49 men had no intervention for three months ( historical controls ) . They then joined the assessment and treatment programme . INTERVENTION -- Four sessions of pelvic floor exercises and bladder retraining supervised by non-specialist nurse who had taken a three week course on assessing and treating uncomplicated incontinence . MAIN OUTCOME MEASURES --Number of patients desiring treatment ; self reported cure , improvement , or deterioration in continence after three months . RESULTS --The question naire achieved a 79 % response . Vali date d responses showed a prevalence of 4.4 % in men and 16.4 % in women aged 35 - 64 . 315 ( 45 % ) of the 700 patients offered assessment refused it and seven had moved away or died , 64 men and 41 women were referred to their general practitioner . 197 of 292 treated women ( 68 % ) reported cure or improvement compared with seven ( 5 % ) of controls . 22 of the 86 men desiring treatment were suitable for intervention by the nurse . Seventeen were cured or improved compared with none of the men in the control group . CONCLUSIONS --About half the people with regular urinary incontinence took up the offer of treatment ( 9.2 % of women and 3.4 % of men in the study population ) . This condition can be effectively managed by a nurse with limited training Regular urinary incontinence affects one in six adult women . However , for the majority , good continence services are difficult to access and few primary care-based assessment and treatment facilities are available . A large r and omised trial of assessment and treatment in primary care using a trained nurse was conducted in Somerset in 1990 . This report summarises the methods and results of the initial study and reports the four-year follow-up results . The results show that 70 per cent of women will gain Output:	Pelvic floor muscle training was better than no treatment or placebo treatments for women with stress or mixed incontinence . ' Intensive ' appeared to be better than ' st and ard ' pelvic floor muscle training . There is insufficient evidence to determine if pelvic floor muscle training is better or worse than other treatments . Evidence of the effect of adding other adjunctive treatments to PFMT ( e.g. vaginal cones , intravaginal resistance ) is equally limited . The effectiveness of biofeedback assisted PFMT is not clear , but on the basis of the evidence available there did not appear to be any benefit over PFMT alone at post treatment assessment . Long-term outcomes of pelvic floor muscle training are unclear . Side effects of pelvic floor muscle training were uncommon and reversible . REVIEW ER 'S CONCLUSIONS Pelvic floor muscle training appeared to be an effective treatment for adult women with stress or mixed incontinence . Pelvic floor muscle training was better than no treatment or placebo treatments . The limitations of the evidence available mean that is difficult to judge if pelvic floor muscle training was better or worse than other treatments . Most trials to date have studied the effect of treatment in younger , premenopausal women .
MS2773	*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 Heroin-assisted treatment has been found to be effective for people with severe opioid dependence who are not interested in or do poorly on methadone maintenance . AIMS To study heroin-assisted treatment in people on methadone who continue intravenous heroin and in those who are heroin dependent but currently not in treatment . METHOD In an open-label multicentre r and omised controlled trial , 1015 people with heroin dependence received a variable dose of injectable heroin ( n=515 ) or oral methadone ( n=500 ) for 12 months . Two response criteria , improvement of physical and /or mental health and decrease in illicit drug use , were evaluated in an intent-to-treat analysis . RESULTS Retention was higher in the heroin ( 67.2 % ) than in the methadone group ( 40.0 % ) and the heroin group showed a significantly greater response on both primary outcome measures . More serious adverse events were found in the heroin group , and were mainly associated with intravenous use . CONCLUSIONS Heroin-assisted treatment is more effective for people with opioid dependence who continue intravenous heroin while on methadone maintenance or who are not enrolled in treatment . Despite a higher risk , it should be considered for treatment resistance under medical supervision Abstract Objective : To evaluate an experimental heroin maintenance programme . Design : R and omised trial . Setting : Outpatient clinic in Geneva , Switzerl and . Subjects : Heroin addicts recruited from the community who were socially marginalised and in poor health and had failed in at least two previous drug treatments . Intervention : Patients in the experimental programme ( n=27 ) received intravenous heroin and other health and psychosocial services . Control patients ( n=24 ) received any other conventional drug treatment ( usually methadone maintenance ) . Main outcome measures : Self reported drug use , health status ( SF-36 ) , and social functioning . Results : 25 experimental patients completed 6 months in the programme , receiving a median of 480 mg of heroin daily . One experimental subject and 10 control subjects still used street heroin daily at follow up ( difference 44 % ; 95 % confidence interval 16 % to 71 % ) . Health status scores that improved significantly more in experimental subjects were mental health ( 0.58 SD ; 0.07 to 1.10 ) , role limitations due to emotional problems ( 0.95 SD ; 0.11 to 1.79 ) , and social functioning ( 0.65 SD ; 0.03 to 1.26 ) . Experimental subjects also significantly reduced their illegal income and drug expenses and committed fewer drug and property related offences . There were no benefits in terms of work , housing situation , somatic health status , and use of other drugs . Unexpectedly , only nine ( 38 % ) control subjects entered the heroin maintenance programme at follow up . Conclusions : A heroin maintenance programme is a feasible and clinical ly effective treatment for heroin users who fail in conventional drug treatment programmes . Even in this population , however , another attempt at methadone maintenance may be successful and help the patient to stop using injectable opioids The effects of maintenance on a narcotic antagonist , naltrexone ( 50 mg/day p.o . ) , or placebo on patterns of operant acquisition and use of heroin were studied under double-blind conditions . Twelve male heroin addict volunteers lived on a clinical research ward for 34 days . After a 9 day drug-free period , naltrexone or placebo were given and heroin ) 40 mg/day ) was available for 10 days . Subjects could earn money ( $ 1.50 ) or heroin ( 10 mg i.v . ) by responding on a second-order schedule of reinforcement [ FR 300 ( FI 1 sec : S ) ] for approximately 90 min . The three naltrexone-maintained subjects took only 2 to 7.5 % of the total heroin available . Two naltrexone subjects stopped heroin self-administration after the 1st or 2nd heroin injection ; the third subject took a 3rd heroin injection on the 8th day of heroin availability . Naltrexone maintenance for 25 consecutive days did not produce adverse side effects . In contrast , the nine placebo naltrexone subjects used 57.5 to 100 % of the total heroin available . Five placebo subjects used all or all but one of the 40 injections available ; four placebo subjects often used less heroin than was available each day . Heroin intoxication did not impair operant performance . Heroin users worked longer hours and earned more purchase points ( P < .05 ) during heroin self-administration and subsequent methadone detoxification than during the drug-free period . Subjects precisely titrated operant work to acquire the desired amount of heroin , then resumed working for money . These data demonstrate the feasibility of using direct measures of drug self-administration behavior to evaluate new pharmacotherapies for heroin abuse and indicate the effectiveness of naltrexone in suppressing heroin self-administration Abstract Objective To determine whether supervised medical prescription of heroin can successfully treat addicts who do not sufficiently benefit from methadone maintenance treatment . Design Two open label r and omised controlled trials . Setting Methadone maintenance programmes in six cities in the Netherl and s. Participants 549 heroin addicts . Interventions Inhalable heroin ( n = 375 ) or injectable heroin ( n = 174 ) prescribed over 12 months . Heroin ( maximum 1000 mg per day ) plus methadone ( maximum 150 mg per day ) compared with methadone alone ( maximum 150 mg per day ) . Psychosocial treatment was offered throughout . Main outcome measures Dichotomous , multidomain response index , including vali date d indicators of physical health , mental status , and social functioning . Results Adherence was excellent with 12 month outcome data available for 94 % of the r and omised participants . With intention to treat analysis , 12 month treatment with heroin plus methadone was significantly more effective than treatment with methadone alone in the trial of inhalable heroin ( response rate 49.7 % v 26.9 % ; difference 22.8 % , 95 % confidence interval 11.0 % to 34.6 % ) and in the trial of injectable heroin ( 55.5 % v 31.2 % ; difference 24.3 % , 9.6 % to 39.0 % ) . Discontinuation of the coprescribed heroin result ed in a rapid deterioration in 82 % ( 94/115 ) of those who responded to the coprescribed heroin . The incidence of serious adverse events was similar across treatment conditions . Conclusions Supervised coprescription of heroin is feasible , more effective , and probably as safe as methadone alone in reducing the many physical , mental , and social problems of treatment resistant heroin addicts Background The objective of this research was to evaluate data from a r and omized clinical trial that tested injectable diacetylmorphine ( DAM ) and oral methadone ( MMT ) for substitution treatment , using a multi-domain dichotomous index , with a Bayesian approach . Methods Sixty two long-term , socially-excluded heroin injectors , not benefiting from available treatments were r and omized to receive either DAM or MMT for 9 months in Granada , Spain . Completers were 44 and data at the end of the study period was obtained for 50 . Participants were determined to be responders or non responders using a multi-domain outcome index accounting for their physical and mental health and psychosocial integration , used in a previous trial . Data was analyzed with Bayesian methods , using information from a similar study conducted in The Netherl and s to select a priori distributions . On adding the data from the present study to up date the a priori information , the distribution of the difference in response rates were obtained and used to build credibility intervals and relevant probability computations . Results In the experimental group ( n = 27 ) , the rate of responders to treatment was 70.4 % ( 95 % CI 53.2 - 87.6 ) , and in the control group ( n = 23 ) , it was 34.8 % ( 95 % CI 15.3 - 54.3 ) . The probability of success in the experimental group using the a posteriori distributions was higher after a proper sensitivity analysis . Almost the whole distribution of the rates difference ( the one for diacetylmorphine minus methadone ) was located to the right of the zero , indicating the superiority of the experimental treatment . Conclusion The present analysis suggests a clinical superiority of injectable diacetylmorphine compared to oral methadone in the treatment of severely affected heroin injectors not benefiting sufficiently from the available treatments . Trial Registration Current Controlled Trials IS RCT Whilst unsupervised injectable methadone and diamorphine treatment has been part of the British treatment system for decades , the numbers receiving injectable opioid treatment ( IOT ) has been steadily diminishing in recent years . In contrast , there has been a recent expansion of supervised injectable diamorphine programs under trial conditions in a number of European and North American cities , although the evidence regarding the safety , efficacy and cost effectiveness of this treatment approach remains equivocal . Recent British clinical guidance indicates that IOT should be a second-line treatment for those patients in high- quality oral methadone treatment who continue to regularly inject heroin , and that treatment be initiated in newly-developed supervised injecting clinics . The R and omised Injectable Opioid Treatment Trial ( RIOTT ) is a multisite , prospect i ve open-label r and omised controlled trial ( RCT ) examining the role of treatment with injected opioids ( methadone and heroin ) for the management of heroin dependence in patients not responding to conventional substitution treatment . Specifically , the study examines whether efforts should be made to optimise methadone treatment for such patients ( e.g. regular attendance , supervised dosing , high oral doses , access to psychosocial services ) , or whether such patients should be treated with injected methadone or heroin . Eligible patients ( in oral substitution treatment and injecting illicit heroin on a regular basis ) are r and omised to one of three conditions : ( 1 ) optimized oral methadone treatment ( Control group ) ; ( 2 ) injected methadone treatment ; or ( 3 ) injected heroin treatment ( with access to oral methadone doses ) . Subjects are followed up for 6-months , with between-group comparisons on an intention-to-treat basis across a range of outcome measures . The primary outcome is the proportion of patients who discontinue regular illicit heroin use ( operationalised as providing > 50 % urine drug screens negative for markers of illicit heroin in months 4 to 6 ) . Secondary outcomes include measures of other drug use , injecting practice s , health and psychosocial functioning , criminal activity , patient satisfaction and incremental cost effectiveness . The study aims to recruit 150 subjects , with 50 patients per group , and is to be conducted in supervised injecting clinics across Engl and Ninety-six confirmed heroin addicts requesting a heroin maintenance prescription were r and omly allocated to treatment with injectable heroin or oral methadone . Progress was monitored throughout the next 12 months by research workers operating independently of the clinic . Heroin can be seen as maintaining the status quo , with the majority continuing to inject heroin regularly and to supplement their maintenance prescription from other sources ; it was associated with a continuing intermediate level of involvement with the drug subculture and criminal activity . Refusal to prescribe heroin while offering oral methadone constituted a more confrontational response and result ed in a higher abstinence rate , but also a greater dependence on illegal sources of drugs for these who continued to inject . Those offered oral methadone tended to polarize toward high or low categories of illegal drug use and involvement with the drug subculture , and were more likely to be arrested during the 12-month follow-up . There was no difference between the two groups in terms of employment , health , or consumption of nonopiate drugs . Refusal to prescribe heroin result ed in a significantly greater drop out from regular treatment Data from a seven-year follow-up study of heroin addicts were analysed to show group trends . Time spent in various activities was quantified for each person for each year of the follow-up period and used to provide a composite life history . Time spent by the sample using drugs has decreased over the follow-up period . The most marked decrease appeared in the use of heroin , but the analysis suggests that a hard core of heroin users still used heroin several years after coming to the clinic . There seems to be an overall congruence between abstinence and non-clinic attendance . For this sample the use of illegal opiates without attending a clinic was relatively rare , and total time spent in hospitals and in prisons was rather small . Death occurred r and omly during the follow-up period AIMS To investigate whether the neonatal abstinence syndrome ( NAS ) is different in children born to women maintained on slow-release morphine , compared with those maintained on methadone , and to compare additional drug consumption in these groups of women . DESIGN , SETTING AND PARTICIPANTS An open , r and omized trial was conducted in an established clinic . Forty-eight pregnant women who presented to the clinic as opiate or polysubstance abusers were enrolled and maintained on either methadone ( 24 women ) or slow-release morphine ( 24 women ) up to and following delivery . The programme included psychosocial therapy and support for their opiate-addicted partners . MEASUREMENTS St and ard urinalysis methods were used to measure consumption of cocaine and benzodiazepines during pregnancy . Injection sites were monitored to indicate additional opiate use . NAS was measured according to Finnegan score and the amount of phenobarbiturates prescribed to alleviate the symptoms . FINDINGS No difference was found in the number of days that NAS was experienced by neonates born to methadone or morphine maintained mothers ( mean = 16 and 21 days , respectively ) . All children were born healthy and no serious complications arose . Fewer benzodiazepines ( p < 0.05 Output:	Results on criminal activity and incarceration were not possible to be pooled but where the outcome were measured results of single studies do provide evidence that heroin provision can reduce criminal activity and incarceration/imprisonment . Social functioning improved in all the intervention groups with heroin groups having slightly better results . If all the studies comparing heroin provision in any conditions vs any other treatment are pooled the direction of effect remain in favour of heroin . AUTHORS ' CONCLUSIONS The available evidence suggests an added value of heroin prescribed alongside flexible doses of methadone for long-term , treatment refractory , opioid users , to reach a decrease in the use of illicit substances , involvement in criminal activity and incarceration , a possible reduction in mortaliity ; and an increase in retention in treatment .
MS2774	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The aim of this study was to evaluate prevalence of obstructive sleep apnea among patients undergoing bariatric surgery and the predictive value of various clinical parameters : body mass index ( BMI ) , neck circumference ( NC ) and the Epworth Sleepiness Scale ( ESS ) . We performed a prospect i ve , multidisciplinary , single-center observational study including all patients on the waiting list for bariatric surgery between June 2009 and June 2010 , irrespective of history or clinical findings . Patients visited our ENT outpatient clinic for patient history , ENT and general examination and underwent a full night polysomnography , unless performed previously . As much as 69.9 % of the patients fulfilled the criteria for OSA ( mean BMI 44.2 ± SD 6.4 kg/m2 ) ; 40.4 % of the patients met the criteria for severe OSA . The regression models found BMI to be the best clinical predictor , while the ROC curve found the NC to be the most accurate predictor of the presence of OSA . The discrepancy of the results and the poor statistical power suggest that all three clinical parameters are inadequate predictors of OSA . In conclusion , in this large patient series , 69.9 % of patients undergoing BS meet the criteria for OSA . More than 40 % of these patients have severe OSA . A mere 13.3 % of the patients were diagnosed with OSA before being placed on the waiting list for BS . On statistical analysis , increased neck circumference , BMI and the ESS were found to be insufficient predictors of the presence of OSA . Polysomnography is an essential component of the preoperative workup of patients undergoing BS . When OSA is found , specific perioperative measures are indicated BACKGROUND Limited data have suggested that sleep-disordered breathing , a condition of repeated episodes of apnea and hypopnea during sleep , is prevalent among adults . Data from the Wisconsin Sleep Cohort Study , a longitudinal study of the natural history of cardiopulmonary disorders of sleep , were used to estimate the prevalence of undiagnosed sleep-disordered breathing among adults and address its importance to the public health . METHODS A r and om sample of 602 employed men and women 30 to 60 years old were studied by overnight polysomnography to determine the frequency of episodes of apnea and hypopnea per hour of sleep ( the apnea-hypopnea score ) . We measured the age- and sex-specific prevalence of sleep-disordered breathing in this group using three cutoff points for the apnea-hypopnea score ( > or = 5 , > or = 10 , and > or = 15 ) ; we used logistic regression to investigate risk factors . RESULTS The estimated prevalence of sleep-disordered breathing , defined as an apnea-hypopnea score of 5 or higher , was 9 percent for women and 24 percent for men . We estimated that 2 percent of women and 4 percent of men in the middle-aged work force meet the minimal diagnostic criteria for the sleep apnea syndrome ( an apnea-hypopnea score of 5 or higher and daytime hypersomnolence ) . Male sex and obesity were strongly associated with the presence of sleep-disordered breathing . Habitual snorers , both men and women , tended to have a higher prevalence of apnea-hypopnea scores of 15 or higher . CONCLUSIONS The prevalence of undiagnosed sleep-disordered breathing is high among men and is much higher than previously suspected among women . Undiagnosed sleep-disordered breathing is associated with daytime hypersomnolence CONTEXT Excess body weight is positively associated with sleep-disordered breathing ( SDB ) , a prevalent condition in the US general population . No large study has been conducted of the longitudinal association between SDB and change in weight . OBJECTIVE To measure the independent longitudinal association between weight change and change in SDB severity . DESIGN Population -based , prospect i ve cohort study conducted from July 1989 to January 2000 . SETTING AND PARTICIPANTS Six hundred ninety r and omly selected employed Wisconsin residents ( mean age at baseline , 46 years ; 56 % male ) who were evaluated twice at 4-year intervals for SDB . MAIN OUTCOME MEASURES Percentage change in the apnea-hypopnea index ( AHI ; apnea events + hypopnea events per hour of sleep ) and odds of developing moderate-to-severe SDB ( defined by an AHI > or = 15 events per hour of sleep ) , with respect to change in weight . RESULTS Relative to stable weight , a 10 % weight gain predicted an approximate 32 % ( 95 % confidence interval [ CI ] , 20%-45 % ) increase in the AHI . A 10 % weight loss predicted a 26 % ( 95 % CI , 18%-34 % ) decrease in the AHI . A 10 % increase in weight predicted a 6-fold ( 95 % CI , 2.2 - 17.0 ) increase in the odds of developing moderate-to-severe SDB . CONCLUSIONS Our data indicate that clinical and public health programs that result in even modest weight control are likely to be effective in managing SDB and reducing new occurrence of SDB Daytime sleepiness , impaired cognitive performance and dysphoric mood are often present in patients with obstructive sleep apnoea syndrome ( SAS ) . This prospect i ve controlled study evaluates the effects of treatment with continuous positive airway pressure ( CPAP ) during 1 yr on daytime functioning in a large group of patients with SAS . The authors studied 80 patients ( mean+/-sem 49+/-1 yrs ) with SAS with a mean apnoea-hypopnoea index of 60+/-2 h-1 , and 80 healthy control subjects matched for sex and age ( 46+/-1 yrs . ) . Measurements were obtained at the beginning of the study and 12+/-1 months later , and included : daytime sleepiness ( Epworth scale ) , depression and anxiety ( Beck tests ) , vigilance ( Steer-Clear ) and reaction time ( Psychometer Vigilance Test 192 ) . Drug , coffee and alcohol intake , as well as the sleep schedule , were also recorded . Results showed that , before treatment , patients were more somnolent ( p<0.001 ) , anxious ( p<0.01 ) and depressed ( p<0.001 ) than control subjects . Also , they had a longer reaction time ( p<0.05 ) and poorer vigilance ( p<0.01 ) . The use of CPAP improved significantly the levels of somnolence ( p<0.0001 ) and vigilance ( p<0.01 ) , but failed to modify anxiety and depression . Reaction time changes were minor . Variables with a potential confounding effect did not change during the study . These results provide firm evidence to substantiate the use of continuous positive airway pressure in patients with sleep apnoea syndrome BACKGROUND Results of clinical studies suggest that there may be a relationship between breathing-related sleep disorders and depressive disorders . This study aims to assess the impact of breathing-related sleep disorder on major depressive disorder in the general population . METHOD A cross-sectional telephone survey was carried out between 1994 and 1999 in the general population of the United Kingdom , Germany , Italy , Portugal , and Spain . A total of 18,980 r and omly selected subjects aged 15 to 100 years and representative of the general population of their respective countries participated in the study . The question naire included a series of questions about sleep quality , breathing-related sleep disorder symptoms , mental disorders , and medical conditions . Data are presented using point prevalence . RESULTS 2.1 % of the subjects were found with obstructive sleep apnea syndrome at the time of the interview , and 2.5 % had some other type of DSM-IV breathing-related sleep disorder diagnosis . The association of DSM-IV breathing-related sleep disorder diagnosis and major depressive disorder diagnosis was found in 0.8 % of the sample . As many as 18 % of individuals with a major depressive disorder diagnosis also have a DSM-IV breathing-related sleep disorders diagnosis , and 17.6 % of subjects with a DSM-IV breathing-related sleep disorders diagnosis have a major depressive disorder diagnosis . Multivariate models showed that even after controlling for obesity and hypertension , the odds of having a DSM-IV breathing-related sleep disorders diagnosis was 5.26 for individuals with a major depressive disorder diagnosis . CONCLUSION About 800 of 100,000 individuals have both a breathing-related sleep disorder and a major depressive disorder . The identification of 1 of these 2 disorders should prompt the investigation of the other disorder since nearly a fifth of them have the other disorder Output:	People with SMI ( particularly MDD ) have a high prevalence of OSA .
MS2775	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The aim of this investigation was to compare root resorption in the same individual after application of continuous intrusive and extrusive forces . In nine patients ( mean age 15.3 years ) , the maxillary first premolars were r and omly intruded or extruded with a continuous force of 100 cN for eight weeks . Eleven maxillary first premolars from six r and omly selected orthodontic patients served as controls . Root resorption was determined using scanning electron microscopy . Quantitative assessment of the percentage of resorbed area of the total root surface was performed on composite micrographs . The severity of root resorption was also assessed by visual scoring of the roots . Root resorption mainly occurred at the apical part of the roots in both experimental groups . A significant difference in root resorption was found between the intruded and the control teeth ( P = .006 ) but not between the extruded and the control teeth . However , the mesial and distal root surfaces showed resorption on 5.78 + /- 3.86 % of the root surface of the intruded teeth and 1.28 + /- 1.24 % of the root surface of the extruded teeth , and this difference was significant ( P = .004 ) . In addition , a large individual variation was found . From this study , it can be concluded that intrusion of teeth causes about four times more root resorption than extrusion . Because the amount of root resorption due to intrusion or extrusion in the same patient is correlated , every clinician should be aware that the extrusion of teeth might also cause root resorption in susceptible patients Background Examination with Cone Beam CT ( CBCT ) is common for localizing maxillary canines with eruption disturbance . The benefits and costs of these examinations are unclear . Objectives To measure : 1 . the proportion of orthodontists ' treatment decisions that were different based on intraoral and panoramic radiography ( M1 ) compared with CBCT and panoramic radiography ( M2 ) ; and 2 . the costs of producing different treatment plans , regarding patients with maxillary canines with eruption disturbance . Subjects and methods Orthodontists participated in a web-based survey and were r and omly assigned to denote treatment decisions and the level of confidence in this decision for four patient cases presented with M1 or M2 at two occasions for the same patient case . Results One hundred and twelve orthodontists made 445 assessment s based on M1 and M2 , respectively . Twenty-four per cent of the treatment decisions were different depending on which method the raters had access to , whereof one case differed significantly from all other cases . The mean total cost per examination was € 99.84 using M1 and € 134.37 using M2 , result ing in an incremental cost per examination of € 34.53 for M2 . Limitations Benefits in terms of number of different treatment decisions must be considered as an intermediate outcome for the effectiveness of a diagnostic method and should be interpreted with caution . Conclusions For the patient cases presented in this study , most treatment decisions were the same irrespective of radiological method . Accordingly , this study does not support routine use of CBCT regarding patients with maxillary canine with eruption disturbance OBJECTIVE : To assess the prevalence of severe external root resorption and its potential risk factors result ing from orthodontic treatment . METHODS : A r and omly selected sample was used . It comprised conventional periapical radiographs taken in the same radiology center for maxillary and m and ibular incisors before and after active orthodontic treatment of 129 patients , males and females , treated by means of the St and ard Edgewise technique . Two examiners measured and defined root resorption according to the index proposed by Lev and er et al. The degree of external apical root resorption was registered defining resorption in four degrees of severity . To assess intra and inter-rater reproducibility , kappa coefficient was used . Chi-square test was used to assess the relationship between the amount of root resorption and patient 's sex , dental arch ( maxillary or m and ibular ) , treatment with or without extraction s , treatment duration , root apex stage ( open or closed ) , root shape , as well as overjet and overbite at treatment onset . RESULTS : Maxillary central incisors had the highest percentage of severe root resorption , followed by maxillary lateral incisors and m and ibular lateral incisors . Out of 959 teeth , 28 ( 2.9 % ) presented severe root resorption . The following risk factors were observed : anterior maxillary teeth , overjet greater than or equal to 5 mm at treatment onset , treatment with extraction s , prolonged therapy , and degree of apex formation at treatment onset . CONCLUSION : This study showed that care must be taken in orthodontic treatment involving extraction s , great retraction of maxillary incisors , prolonged therapy , and /or completely formed apex at orthodontic treatment onset OBJECTIVE To evaluate the perception of Greek and Swedish orthodontic practitioners regarding the possible occurrence and prognosis of root resorption occurring during orthodontic treatment and to estimate practitioners ' approaches to the diagnosis of preexisting root resorption , screening of prevalence , and treatment planning approach when moderate or severe root resorption is present . MATERIAL S AND METHODS Question naires were received from r and omly selected Greek ( n = 90 ) and Swedish ( n = 106 ) practitioners . Topics of the questions included ( a ) the presence of history ; ( b ) the radiographic evaluation of root resorption before , during , and after treatment ; ( c ) the treatment approach of initial prevention and protocol s in cases of radiographic diagnosis of root resorption during treatment . RESULTS Of the respondents , 47.1 % of the Swedish practitioners and 32.3 % of the Greek practitioners use periapical and panoramic radiographs to diagnose root resorption , mostly in the anterior region . Both groups recognize trauma , root form , and oral habits as predisposing factors . The majority of Swedish orthodontists perform radiographic follow-up in the first 6 months . In contrast , the Greek orthodontists perform it at 1 year or at the end of treatment . The treatment approach for root resorption that is most frequently used by Swedish orthodontists is altering the treatment plan , using light forces , and allowing resting periods , while the Greek orthodontists most frequently use lighter forces and reduce the total duration of the treatment . CONCLUSIONS Because there is no specific approach offered in the literature , the prevention and treatment re assessment in cases of root resorption relies on individual practitioner perception 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 INTRODUCTION There is still ambiguity about whether continuous or intermittent orthodontic forces produce more root resorption . This prospect i ve r and omized clinical trial was design ed to compare root resorption with these 2 force application patterns . METHODS The sample consisted of 16 maxillary first premolars from 8 patients who required bilateral extraction s as part of their orthodontic treatment . In each subject , a fixed experimental appliance was placed on the maxillary teeth on each side , allowing a buccally directed force . The force was generated by a segmental wire of beta-titanium-molybdenum alloy . The first premolar on 1 side received a buccally directed continuous force , and the contralateral premolar received intermittent force . The initial force magnitude for both sides was 225 cN. After 14 days of initial continuous force , the intermittent force application was obtained with subsequently repeated periods until the end of the eighth week of a 3-day rest period followed by a 4-day force application period . Force levels were set to 225 cN at each patient visit . After the experimental period of 8 weeks , the teeth were extracted under a strict protocol to prevent root surface damage and analyzed with a microcomputed-tomography scan system , and specially design ed software was used for direct volumetric measurements . RESULTS Intermittent force produced less root resorption than continuous force ( P < 0.05 ) . Analysis by position showed that the buccal-cervical region had significantly more root resorption than the other positions ( P < 0.001 ) , corresponding to a region of compression generated by tipping . CONCLUSIONS The application of intermittent orthodontic forces of 225 cN for 8 weeks ( 14 days of force application , 3 days of rest , then 4 days of force application repeated for 6 weeks ) caused less root resorption than continuous forces of 225 cN for 8 weeks . Although it might not be clinical ly practical , compared with continuous forces , intermittent forces might be a safer method to prevent significant root resorption . This regimen , however , could compromise the efficiency of tooth movement Aim : The aim of this prospect i ve study was to radiographically assess root morphology changes in maxillary and m and ibular premolars following Herbst appliance treatment . Patients and Methods : Twenty-five consecutive adolescents ( 19 boys and six girls , mean age 13.08 years ) with Class II , Division 1 malocclusion were treated with the b and ed Herbst appliance for a mean period of 13.16 months . Periapical radiographs of the upper and lower premolars were obtained before appliance insertion and immediately after appliance removal using the parallel technique . All radiographs were scanned , digitized and analyzed using appropriately adjusted cephalometric software . The pre- and post-treatment length and area of the first and second maxillary and m and ibular premolar roots were calculated . Statistical analysis included paired t-tests to evaluate pre- and posttreatment changes , and independent t-tests to compare the pre and post-treatment differences between the first and the second premolars , which served as controls . The level of significance was set at p ≤ 0.05 for all tests . Results : No statistically significant decrease in premolar root lengths or areas was noted following removal of the Herbst appliance . We observed a statistically-significant decrease in the root area of the first m and ibular premolars compared to that of the second m and ibular premolars . Conclusions : Although we observed no statistically-significant root morphology changes in the first and second premolars following Herbst appliance treatment , the m and ibular first premolars revealed significantly more root resorption than did the m and ibular second premolars . ZusammenfassungZiel : Ziel dieser prospektiven Studie war , radiologische Veränderungen der Wurzelmorphologie an Oberkiefer- und Unterkieferprämolaren nach einer Beh and lung mit der Herbst-Apparatur nachzuweisen . Patienten und Method ik:25 aufein and er folgende jugendliche Patienten ( 19 Jungen und sechs Mädchen , mittleres Alter 13,08 Jahre ) mit einer Klasse-II/1-Anomalie wurden i m Schnitt für 13,16 Monate mit einem an Bändern befestigten Herbst-Scharnier beh and elt . Periapikale Röntgenaufnahmen der oberen und unteren Prämolaren wurden vor dem Einsetzen und unmittelbar nach der Entfernung der Apparatur mittels der Paralleltechnik angefertigt . Alle Röntgenaufnahmen wurden eingescannt , digitalisiert und mittels einer adäquat angepassten kephalometrischen Software analysiert . Die Wurzellänge und -fläche der ersten und zweiten Ober- und Unterkieferprämolaren wurden sowohl vor als auch nach der Beh and lung berechnet . Die statistische Analyse enthielt paarige t-Tests zur Evaluation der eingetretenen Veränderungen und unabhängige t-Tests , um diese Veränderungen bei den ersten Prämolaren mit denen der zweiten Prämolaren , die als Kontrollgruppe dienten , zu vergleichen . Das Signifikanz niveau wurde für alle Tests auf p ≤ 0,05 gesetzt . Ergebnisse : Es wurde keine statistisch signifikante Abnahme der Wurzellänge und -fläche der Prämolaren nach Entfernung der Herbst-Apparatur nachgewiesen . Eine statistisch signifikante Abnahme der Wurzelfläche der ersten unteren Pr Output:	Statistically significant differences in OIRR were found according to tooth type or jaw , inclusion of extraction s , treatment duration , and diagnostic accuracy of the CBCT . Conclusions Based on the results of this study , CBCT seems to be a reliable tool to examine OIRR during or at the end of orthodontic treatment . Although the average OIRR measured with CBCT seems to lack clinical relevance , there are certain factors that may affect OIRR following orthodontic treatment .
MS2776	*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 This study showed that combination of strength , balance , agility and jumping training prevented functional decline and bone fragility in home-dwelling elderly women . The finding supports the idea that it is possible to maintain good physical functioning by multi-component exercise program and thus postpone the age-related functional problems . Introduction This 1-year r and omized , controlled exercise intervention trial assessed the effects of two different training programs and their combination on physical functioning and bone in home-dwelling elderly women . Methods One hundred and forty-nine healthy women aged 70–78 years were r and omly assigned into : group 1—resistance training ( RES ) , group 2—balance-jumping training ( BAL ) , group 3—combination of resistance and balance-jumping training ( COMB ) , and group 4—controls ( CON ) . Self-rated physical functioning , leg extensor force , dynamic balance , and bone mass and structure were measured . Results Self-rated physical functioning improved in the COMB group , but was reduced in the CON group ; the mean inter-group difference was 10 % ( 95 % CI : 0–22 % ) . Mean increase in the leg extensor force was higher in the RES ( 14 % ; 4–25 % ) and COMB ( 13 % ; 3–25 % ) compared with the CON groups . Dynamic balance improved in the BAL ( 6 % ; 1–11 % ) and in the COMB ( 8 % ; 3–12 % ) groups . There were no inter-group differences in BMC at the proximal femur . In those COMB women who trained at least twice a week , the tibial shaft structure weakened 2 % ( 0–4 % ) less than those in the CON group . Conclusions Strength , balance , agility , and jumping training ( especially in combination ) prevented functional decline in home-dwelling elderly women . In addition , positive effects seen in the structure of the loaded tibia indicated that exercise may also play a role in preventing bone fragility Summary This study showed that about a half of the exercise-induced gain in dynamic balance and bone strength was maintained one year after cessation of the supervised high-intensity training of home-dwelling elderly women . However , to maintain exercise-induced gains in lower limb muscle force and physical functioning , continued training seems necessary . Introduction Maintenance of exercise-induced benefits in physical functioning and bone structure was assessed one year after cessation of 12-month r and omized controlled exercise intervention . Methods Originally 149 healthy women 70–78 years of age participated in the 12-month exercise RCT and 120 ( 81 % ) of them completed the follow-up study . Self-rated physical functioning , dynamic balance , leg extensor force , and bone structure were assessed . Results During the intervention , exercise increased dynamic balance by 7 % in the combination resistance and balance-jumping training group ( COMB ) . At the follow-up , a 4 % ( 95 % CI : 1–8 % ) gain compared with the controls was still seen , while the exercise-induced isometric leg extension force and self-rated physical functioning benefits had disappeared . During the intervention , at least twice a week trained COMB subjects obtained a significant 2 % benefit in tibial shaft bone strength index compared to the controls . A half of this benefit seemed to be maintained at the follow-up . Conclusions Exercise-induced benefits in dynamic balance and rigidity in the tibial shaft may partly be maintained one year after cessation of a supervised 12-month multi-component training in initially healthy elderly women . However , to maintain the achieved gains in muscle force and physical functioning , continued training seems necessary UNLABELLED We prospect ively examined vBMD and structural bone parameters assessed by QCT among participants of the InCHIANTI study over a 6-yr follow-up . Periosteal apposition occurred both in men and women . Endocortical resorption causes bone loss in older women despite periosteal apposition . INTRODUCTION To address the hypothesis that age-related changes in BMD and bone geometry may be different in men and women , we prospect ively examined volumetric BMD ( vBMD ) and structural bone parameters assessed by QCT among participants of the InCHIANTI study over a 6-yr follow-up . MATERIAL S AND METHODS Three hundred forty-five men and 464 women 21 - 102 yr of age from the InCHIANTI study , a population -based study in Tuscany , Italy , were included . Tibial QCT bone parameters were measured at enrollment ( 1998 - 2000 ) and at 3- ( 2001 - 2003 ) and 6-yr ( 2004 - 2006 ) follow-ups . RESULTS Periosteal apposition occurred both in men and women . The annual rate of bone periosteal apposition was higher in younger than in older men , whereas in women , the rate of apposition was homogenous across age groups . The age-related medullary expansion , expression of endocortical resorption , was significantly higher in women compared with men . In women , but not in men , accelerated endocortical resorption not sufficiently balanced by periosteal apposition caused accelerated loss in cortical bone mass . The cross-sectional moment of inertia decreased progressively over the life span in both sexes . CONCLUSIONS Endocortical resorption causes bone loss in older women despite periosteal apposition . Obtaining a balance between endocortical resorption and periosteal apposition should be the target for interventions aim ed to decrease bone loss and prevent osteoporosis in older women UNLABELLED The increase in bone fragility after menopause results from reduced periosteal bone formation and increased endocortical resorption . Women with highest remodeling had greatest loss of bone mass and estimated bone strength , whereas those with low remodeling lost less bone and maintained estimated bone strength . INTRODUCTION Bone loss from the inner ( endocortical ) surface contributes to bone fragility , whereas deposition of bone on the outer ( periosteal ) surface is believed to be an adaptive response to maintain resistance to bending . MATERIAL S AND METHODS To test this hypothesis , changes in bone mass and estimated indices of bone geometry and strength of the one-third distal radius , bone turnover markers , and fracture incidence were measured annually in 821 women 30 - 89 years of age for 7.1 + /- 2.5 years . The analyses were made in 151 premenopausal women , 33 perimenopausal women , 279 postmenopausal women , and 72 postmenopausal women receiving hormone replacement therapy ( HRT ) . RESULTS In premenopausal women , periosteal apposition increased the radius width , partly off setting endocortical resorption ; therefore , the estimated cortical thickness decreased . Outward displacement of the thinner cortex maintained bone mass and cortical area and increased estimated bending strength . Estimated endocortical resorption accelerated during perimenopause , whereas periosteal apposition decreased . Further cortical thinning occurred , but estimated bending strength was maintained by modest outward cortical displacement . Endocortical resorption accelerated further during the postmenopausal years , whereas periosteal apposition declined further ; cortices thinned , but because outward displacement was minimal , estimated cortical area and bending strength now decreased . Women with highest remodeling had the greatest loss of bone mass and strength . Women with low remodeling lost less bone and maintained estimated bone strength . In HRT-treated women , loss of bone strength was partly prevented . These structural indices predicted incident fractures ; a 1 SD lower section modulus doubled fracture risk . CONCLUSIONS Periosteal apposition does not increase after menopause to compensate for bone loss ; it decreases . Bone fragility of osteoporosis is a consequence of reduced periosteal bone formation and increased endocortical resorption . Underst and ing the mechanisms of the age-related decline in periosteal apposition will identify new therapeutic targets . On the basis of our results , it may be speculated that the stimulation of periosteal apposition will increase bone width and improve skeletal strength CONTEXT Despite decades of accumulated observational evidence , the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain . OBJECTIVE To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States . DESIGN Estrogen plus progestin component of the Women 's Health Initiative , a r and omized controlled primary prevention trial ( planned duration , 8.5 years ) in which 16608 postmenopausal women aged 50 - 79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993 - 1998 . INTERVENTIONS Participants received conjugated equine estrogens , 0.625 mg/d , plus medroxyprogesterone acetate , 2.5 mg/d , in 1 tablet ( n = 8506 ) or placebo ( n = 8102 ) . MAIN OUTCOMES MEASURES The primary outcome was coronary heart disease ( CHD ) ( nonfatal myocardial infa rct ion and CHD death ) , with invasive breast cancer as the primary adverse outcome . A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke , pulmonary embolism ( PE ) , endometrial cancer , colorectal cancer , hip fracture , and death due to other causes . RESULTS On May 31 , 2002 , after a mean of 5.2 years of follow-up , the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits . This report includes data on the major clinical outcomes through April 30 , 2002 . Estimated hazard ratios ( HRs ) ( nominal 95 % confidence intervals [ CIs ] ) were as follows : CHD , 1.29 ( 1.02 - 1.63 ) with 286 cases ; breast cancer , 1.26 ( 1.00 - 1.59 ) with 290 cases ; stroke , 1.41 ( 1.07 - 1.85 ) with 212 cases ; PE , 2.13 ( 1.39 - 3.25 ) with 101 cases ; colorectal cancer , 0.63 ( 0.43 - 0.92 ) with 112 cases ; endometrial cancer , 0.83 ( 0.47 - 1.47 ) with 47 cases ; hip fracture , 0.66 ( 0.45 - 0.98 ) with 106 cases ; and death due to other causes , 0.92 ( 0.74 - 1.14 ) with 331 cases . Corresponding HRs ( nominal 95 % CIs ) for composite outcomes were 1.22 ( 1.09 - 1.36 ) for total cardiovascular disease ( arterial and venous disease ) , 1.03 ( 0.90 - 1.17 ) for total cancer , 0.76 ( 0.69 - 0.85 ) for combined fractures , 0.98 ( 0.82 - 1.18 ) for total mortality , and 1.15 ( 1.03 - 1.28 ) for the global index . Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events , 8 more strokes , 8 more PEs , and 8 more invasive breast cancers , while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures . The absolute excess risk of events included in the global index was 19 per 10 000 person-years . CONCLUSIONS Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women . All-cause mortality was not affected during the trial . The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases , and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD Introduction Bone fragility and decreased functional performance are risk factors for osteoporotic fractures . The influence of long-term recreational gymnastics on the maintenance of bone rigidity and physical performance was evaluated . Methods One hundred and seven gymnasts and 110 referents ( 93 % of the original sample ) participated in this 6-year prospect i ve study . Analysis of covariance ( ANCOVA ) was used to estimate the between-group differences and changes by time , and regression analyses to find predictors for changes . Results In both groups agility and leg extensor power decreased by over 3 % and 10 % , respectively , but the original between-group differences , favoring the gymnasts , persisted . Proximal femur bone mineral content ( BMC ) decreased approximately 0.5 % per year in both groups , and femoral neck section modulus decreased . Trabecular density of the distal tibia declined only marginally , and cortical area of the tibial midshaft remained unchanged , while cortical density decreased about 2 % in both groups . After adjustment by age , height , weight , change in weight , and follow-up time , antiresorptive medication and high calcium intake accounted most for the maintenance of bone rigidity . Conclusions In spite of similar rates of decline in bone characteristics and physical performance , the recreational gymnasts ’ overall physical condition was comparable to the level that their less active referents had Output:	Exercise effects appear to be modest , site-specific , and preferentially influence cortical rather than trabecular components of bone . Exercise type also plays a role , with the most prominent mass and geometric changes being observed in response to high-impact loading exercise . Exercise appears to positively influence bone mass and geometry in postmenopausal women .
MS2777	*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 cluster r and omized trial , Kojo Yeboah-Antwi and colleagues find that integrated management of malaria and pneumonia in children under five by community health workers is both feasible and effective Objective To test in West Africa the impact of rapid diagnostic tests on the prescription of antimalarials and antibiotics both where microscopy is used for the diagnosis of malaria and in clinical ( peripheral ) setting s that rely on clinical diagnosis . Design R and omised , controlled , open label clinical trial . Setting Four clinics in the rural Dangme West district of southern Ghana , one in which microscopy is used for diagnosis of malaria ( “ microscopy setting ” ) and three where microscopy is not available and diagnosis of malaria is made on the basis of clinical symptoms ( “ clinical setting ” ) . Participants Patients with suspected malaria . Interventions Patients were r and omly assigned to either a rapid diagnostic test or the current diagnostic method at the clinic ( microscopy or clinical diagnosis ) . A blood sample for a research microscopy slide was taken for all patients . Main outcome measures The primary outcome was the prescription of antimalarials to patients of any age whose double read research slide was negative for malaria . The major secondary outcomes were the correct prescription of antimalarials , the impact of test results on antibiotic prescription , and the correct prescription of antimalarials in children under 5 years . Results Of the 9236 patients screened , 3452 were r and omised in the clinical setting and 3811 in the microscopy setting . Follow-up to 28 days was 97.6 % ( 7088/7263 ) . In the microscopy setting , 722 ( 51.6 % ) of the 1400 patients with negative research slides in the rapid diagnostic test arm were treated for malaria compared with 764 ( 55.0 % ) of the 1389 patients in the microscopy arm ( adjusted odds ratio 0.87 , 95 % CI 0.71 to 1.1 ; P=0.16 ) . In the clinical setting , 578 ( 53.9 % ) of the 1072 patients in the rapid diagnostic test arm with negative research slides were treated for malaria compared with 982 ( 90.1 % ) of the 1090 patients with negative slides in the clinical diagnosis arm ( odds ratio 0.12 , 95 % CI 0.04 to 0.38 ; P=0.001 ) . The use of rapid diagnostic tests led to better targeting of antimalarials and antibiotics in the clinical but not the microscopy setting , in both children and adults . There were no deaths in children under 5 years at 28 days follow-up in either arm . Conclusion Where microscopy already exists , introducing rapid diagnostic tests had limited impact on prescriber behaviour . In setting s where microscopy was not available , however , using rapid diagnostic tests led to a significant reduction in the overprescription of antimalarials , without any evidence of clinical harm , and to better targeting of antibiotics . Trial registration Clinical Trials.gov NCT00493922 Background Early diagnosis and prompt , effective treatment of uncomplicated malaria is critical to prevent severe disease , death and malaria transmission . We assessed the impact of rapid malaria diagnostic tests ( RDTs ) by community health workers ( CHWs ) on provision of artemisinin-based combination therapy ( ACT ) and health outcome in fever patients . Methodology /Principal Findings Twenty-two CHWs from five villages in Kibaha District , a high-malaria transmission area in Coast Region , Tanzania , were trained to manage uncomplicated malaria using RDT aided diagnosis or clinical diagnosis ( CD ) only . Each CHW was r and omly assigned to use either RDT or CD the first week and thereafter alternating weekly . Primary outcome was provision of ACT and main secondary outcomes were referral rates and health status by days 3 and 7 . The CHWs enrolled 2930 fever patients during five months of whom 1988 ( 67.8 % ) presented within 24 hours of fever onset . ACT was provided to 775 of 1457 ( 53.2 % ) patients during RDT weeks and to 1422 of 1473 ( 96.5 % ) patients during CD weeks ( Odds Ratio ( OR ) 0.039 , 95 % CI 0.029–0.053 ) . The CHWs adhered to the RDT results in 1411 of 1457 ( 96.8 % , 95 % CI 95.8–97.6 ) patients . More patients were referred on inclusion day during RDT weeks ( 10.0 % ) compared to CD weeks ( 1.6 % ) . Referral during days 1–7 and perceived non-recovery on days 3 and 7 were also more common after RDT aided diagnosis . However , no fatal or severe malaria occurred among 682 patients in the RDT group who were not treated with ACT , supporting the safety of withholding ACT to RDT negative patients . Conclusions / Significance RDTs in the h and s of CHWs may safely improve early and well-targeted ACT treatment in malaria patients at community level in Africa . Trial registration Clinical Trials.gov Objective To compare rapid diagnostic tests ( RDTs ) for malaria with routine microscopy in guiding treatment decisions for febrile patients . Design R and omised trial . Setting Outpatient departments in northeast Tanzania at varying levels of malaria transmission . Participants 2416 patients for whom a malaria test was requested . Intervention Staff received training on rapid diagnostic tests ; patients sent for malaria tests were r and omised to rapid diagnostic test or routine microscopy Main outcome measure Proportion of patients with a negative test prescribed an antimalarial drug . Results Of 7589 outpatient consultations , 2425 ( 32 % ) had a malaria test requested . Of 1204 patients r and omised to microscopy , 1030 ( 86 % ) tested negative for malaria ; 523 ( 51 % ) of these were treated with an antimalarial drug . Of 1193 patients r and omised to rapid diagnostic test , 1005 ( 84 % ) tested negative ; 540 ( 54 % ) of these were treated for malaria ( odds ratio 1.13 , 95 % confidence interval 0.95 to 1.34 ; P=0.18 ) . Children aged under 5 with negative rapid diagnostic tests were more likely to be prescribed an antimalarial drug than were those with negative slides ( P=0.003 ) . Patients with a negative test by any method were more likely to be prescribed an antibiotic ( odds ratio 6.42 , 4.72 to 8.75 ; P<0.001 ) . More than 90 % of prescriptions for antimalarial drugs in low-moderate transmission setting s were for patients for whom a test requested by a clinician was negative for malaria . Conclusions Although many cases of malaria are missed outside the formal sector , within it malaria is massively over-diagnosed . This threatens the sustainability of deployment of artemisinin combination treatment , and treatable bacterial diseases are likely to be missed . Use of rapid diagnostic tests , with basic training for clinical staff , did not in itself lead to any reduction in over-treatment for malaria . Interventions to improve clinicians ' management of febrile illness are essential but will not be easy . Trial registration Clinical trials NCT00146796 Background Presumptive treatment of all febrile patients with anti-malarials leads to massive over-treatment . The aim was to assess the effect of implementing malaria rapid diagnostic tests ( m RDTs ) on prescription of anti-malarials in urban Tanzania . Methods The design was a prospect i ve collection of routine statistics from ledger books and cross-sectional surveys before and after intervention in r and omly selected health facilities ( HF ) in Dar es Salaam , Tanzania . The participants were all clinicians and their patients in the above health facilities . The intervention consisted of training and introduction of m RDTs in all three hospitals and in six HF . Three HF without m RDTs were selected as matched controls . The use of routine m RDT and treatment upon result was advised for all patients complaining of fever , including children under five years of age . The main outcome measures were : ( 1 ) anti-malarial consumption recorded from routine statistics in ledger books of all HF before and after intervention ; ( 2 ) anti-malarial prescription recorded during observed consultations in cross-sectional surveys conducted in all HF before and 18 months after m RDT implementation . Results Based on routine statistics , the amount of artemether-lumefantrine blisters used post-intervention was reduced by 68 % ( 95%CI 57 - 80 ) in intervention and 32 % ( 9 - 54 ) in control HF . For quinine vials , the reduction was 63 % ( 54 - 72 ) in intervention and an increase of 2.49 times ( 1.62 - 3.35 ) in control HF . Before- and -after cross-sectional surveys showed a similar decrease from 75 % to 20 % in the proportion of patients receiving anti-malarial treatment ( Risk ratio 0.23 , 95%CI 0.20 - 0.26 ) . The cluster r and omized analysis showed a considerable difference of anti-malarial prescription between intervention HF ( 22 % ) and control HF ( 60 % ) ( Risk ratio 0.30 , 95%CI 0.14 - 0.70 ) . Adherence to test result was excellent since only 7 % of negative patients received an anti-malarial . However , antibiotic prescription increased from 49 % before to 72 % after intervention ( Risk ratio 1.47 , 95%CI 1.37 - 1.59 ) . Conclusions Programmatic implementation of m RDTs in a moderately endemic area reduced drastically over-treatment with anti-malarials . Properly trained clinicians with adequate support complied with the recommendation of not treating patients with negative results . Implementation of m RDT should be integrated h and -in-h and with training on the management of other causes of fever to prevent irrational use of antibiotics OBJECTIVES To assess if the clinical outcome of patients treated after performing a Rapid Diagnostic Test for malaria ( RDT ) is at least equivalent to that of controls ( treated presumptively without test ) and to determine the impact of the introduction of a malaria RDT on clinical decisions . METHODS R and omized , multi-centre , open clinical trial in two arms in 2006 at the end of the dry and of the rainy season in 10 peripheral health centres in Burkina Faso : one arm with use of RDT before treatment decision , one arm managed clinical ly . Primary endpoint : persistence of fever at day 4 . Secondary endpoints : frequency of malaria treatment and of antibiotic treatment . RESULTS A total of 852 febrile patients were recruited in the dry season and 1317 febrile patients in the rainy season , and r and omized either to be su bmi tted to RDT ( P_RTD ) or to be managed presumptively ( P_CLIN ) . In both seasons , no significant difference was found between the two r and omized groups in the frequency of antimalarial treatment , nor of antibiotic prescription . In the dry season , 80.8 % and 79.8 % of patients with a negative RDT were nevertheless diagnosed and treated for malaria , and so were 85.0 % and 82.6 % negative patients in the rainy season . In the rainy season only , both diagnosis and treatment of other conditions were significantly less frequent in RDT positive vs. negative patients ( 48.3 % vs. 61.4 % and 46.2 % vs. 59.9 % , P = 0.00 and 0.00 , respectively ) . CONCLUSION Our study was inconclusive on RDT safety ( clinical outcome in the two r and omized groups ) , because of an exceedingly and unexpectedly low compliance with the negative test result . Further research is needed on best strategies to promote adherence and on the safety of a test based strategy compared with the current , presumptive treatment strategy Shortly after Kenya introduced artemether-lumefantrine ( AL ) for first-line treatment of uncomplicated malaria , we conducted a pre-post cluster r and omized controlled trial to assess the effect of providing malaria rapid diagnostic tests ( RDTs ) on recommended treatment ( patients with malaria prescribed AL ) and overtreatment ( patients without malaria prescribed AL ) in out patients > /= 5 years old . Sixty health facilities were r and omized to receive either RDTs plus training , guidelines , and supervision ( TGS ) or TGS alone . Of 1,540 patients included in the analysis , 7 % had uncomplicated malaria . The provision of RDTs coupled with TGS emphasizing AL use only after laboratory confirmation of malaria reduced recommended treatment by 63%-points ( P = 0.04 ) , because diagnostic test use did not change ( -2%-points ) , but health workers significantly reduced presumptive treatment with AL for patients with a clinical diagnosis of malaria who did not undergo testing ( -36%-points ; P = 0.03 ) . Health workers generally adhered to RDT results when prescribing AL : 88 % of RDT-positive and 9 % of RDT-negative patients were treated with AL , respectively . Overtreatment was low in both arms and was not significantly reduced by the provision of RDTs ( -12%-points , P = 0.30 ) . RDTs could potentially improve malaria case management , but we urgently need to develop more effective strategies for implementing guidelines before large scale implementation Output:	Authors ' conclusions Algorithms incorporating RDTs can substantially reduce antimalarial prescribing if health workers adhere to the test results . Introducing RDTs has not been shown to improve health outcomes for patients , but adherence to the test result does not seem to result in worse clinical outcomes than presumptive treatment . Concentrating on improving the care of RDT negative patients could improve health outcomes in febrile children
MS2778	*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 present study aim ed to extend the literature on text messaging interventions involved in promoting healthy eating behaviours . The theoretical framework was the Theory of Planned Behaviour ( TPB ) . A r and omized controlled trial was used to test the impact of daily text messages compared to no message ( groups ) for reducing processed meat consumption ( PMC ) over a 2 week period , testing the sequential mediation role of anticipated regret and intention on the relationship between groups and PMC reduction . PMC and TPB variables were assessed both at Time 1 and Time 2 . Participants were Italian undergraduates ( at Time 1 N = 124 ) r and omly allocated to control and message condition groups . Undergraduates in the message condition group received a daily SMS , which focused on anticipated regret and urged them to self-monitor PMC . Participants in the control group did not receive any message . Those who completed all measures at both time points were included in the analyses ( N = 112 ) . Findings showed that a daily messaging intervention , controlling for participants ' past behaviour , reduced self-reported consumption of PMC . Mediation analyses indicated partial serial mediation via anticipated regret and intentions . The current study provided support for the efficacy of a daily messaging intervention targeting anticipated regret and encouraging self-monitoring in decreasing PMC . Outcomes showed the important mediating role of anticipated regret and intentions for reducing PMC RATIONALE The present studies aim ed to contribute to the literature on psychological variables involved in reducing red meat consumption ( RMC ) . OBJECTIVE Study 1 investigated whether the theory of planned behaviour ( TPB ) , plus healthy-eating and meat-eating identities , could explain intentions to reduce RMC . Study 2 evaluated the effectiveness of an SMS text message intervention on self-monitoring to reduce RMC . METHODS In Study 1 , data were collected daily using online food diaries for one week and a TPB question naire . Study 2 was a r and omised controlled trial assessing pre- and post-RMC and TPB constructs by online food diaries and question naires over a one-week period . Participants were Italian undergraduates in each study ( Study 1 : N = 405 ; Study 2 : N = 244 ) . In Study 2 , participants were r and omly allocated to control and message condition groups . Participants in the message condition group received a daily SMS , which reminded them to monitor RMC , while participants in the control group did not receive any message . Only students who completed all measures were considered in the analyses ( Study 1 : N = 342 ; Study 2 : N = 228 ) . RESULTS Study 1 showed that affective and instrumental attitudes , perceived behavioural control , and meat-eating identity explained intentions to reduce RMC , while subjective norm , past behaviour , and healthy-eating identity did not . Study 2 showed that an SMS intervention was effective in increasing intentions and reducing RMC . Mediation analyses indicated partial serial mediation through healthy-eating and meat-eating identities and intentions . CONCLUSION The present studies provide support for the predictive validity of TPB in explaining intentions to reduce RMC and for the efficacy of an SMS intervention targeting self-monitoring in reducing RMC . Findings confirmed the important role of eating identities in explaining intentions to reduce RMC and in changing this behaviour Disease risk factors identified in epidemiological studies serve as important public health tools , helping clinicians identify individuals who may benefit from more aggressive screening or risk-modification procedures , allowing policymakers to prioritize intervention programs , and encouraging at-risk individuals to modify behavior and improve their health . These factors have been based primarily on evidence from cross-sectional and prospect i ve studies , as most do not lend themselves to r and omized trials . While some risk factors are not modifiable , eating habits are subject to change through both individual action and broader policy initiatives . Meat consumption has been frequently investigated as a variable associated with diabetes risk , but it has not yet been described as a diabetes risk factor . In this article , we evaluate the evidence supporting the use of meat consumption as a clinical ly useful risk factor for type 2 diabetes , based on studies evaluating the risks associated with meat consumption as a categorical dietary characteristic ( i.e. , meat consumption versus no meat consumption ) , as a scalar variable ( i.e. , gradations of meat consumption ) , or as part of a broader dietary pattern With growing awareness that sustainable consumption is important for quality of life on earth , many individuals intend to act more sustainably . In this regard , interest in reducing meat consumption is on the rise . However , people often do not translate intentions into actual behavior change . To address this intention-behavior gap , we tested the self-regulation strategy of mental contrasting with implementation intentions ( MCII ) . Here , people identify and imagine a desired future and current obstacles st and ing in its way . They address the obstacles with if-then plans specifying when , where , and how to act differently . In a 5-week r and omized controlled experimental study , we compared an information + MCII intervention with an information-only control intervention . As hypothesized , only MCII participants ’ intention of reducing their meat consumption was predictive of their actual reduction , while no correspondence between intention and behavior change was found for control participants . Participants with a moderate to strong intention to reduce their meat consumption reduced it more in the MCII than in the control condition . Thus , MCII helped to narrow the intention-behavior gap and supported behavior change for those holding moderate and strong respective intentions Background Swaps are often used to encourage healthier food choices , but there is little evidence of their effectiveness . The current study assessed the impact of offering swaps on groceries purchased within a bespoke online supermarket ; specifically the objective was to measure the impact on energy density ( ED ) of food purchases following the offer of lower ED alternatives ( a ) at point of selection or at checkout , and ( b ) with or without explicit consent to receive swap prompts . Method Participants were asked to complete a 12-item shopping task within an online shopping platform , developed for study ing food purchasing . 1610 adults were r and omly assigned to a no swap control condition or to one of four interventions : consented swaps at selection ; consented swaps at checkout ; imposed swaps at selection ; or imposed swaps at checkout . Each swap presented two lower ED options from the same category as the participant ’s chosen food . Swap acceptance rate and purchased food ED were the primary outcomes . Results Of the mean 12.36 ( SD 1.26 ) foods purchased , intervention participants were offered a mean of 4.1 ( SD 1.68 ) swaps , with the potential to reduce the ED of purchased food ( effect ( 95 % CI ) : −83 kJ/100 g ( −110 – -56 ) , p = < 0.0001 ) . A median of one swap ( IQR 0 to 2 ) was accepted , not significantly reducing the purchased food ED ( effect ( 95 % CI ) : −24 kJ/100 g ( 4 – -52 ) , p = 0.094 ) . More swaps were accepted when offered at selection than at checkout ( OR ( 95 % CI ) = 1.224 ( 1.11 – 1.35 ) , p < 0.0001 ) , but no differences were seen with consent . Purchased food ED was unaffected by point of swap or consent , but reduced with number of swaps accepted ( effect per swap ( 95 % CI ) = −24 kJ/100 g ( −35 – -14 ) , p < 0.0001 ) . Conclusion Within category swaps did not reduce the ED of food purchases reflecting the observation that the use of swaps within an on-line shopping platform offered small potential gains in ED and a minority was accepted OBJECTIVE To investigate the feasibility and short-term effectiveness of a lifestyle intervention for colorectal cancer ( CRC ) survivors . METHODS CanChange was telephone-delivered to 20 CRC survivors by health coaches over 6 weeks supported by an interactive participant h and book . We assessed program feasibility ( program retention and satisfaction ) and health outcomes [ CRC-specific symptoms ( fatigue , nausea , diarrhoea ) , quality of life ( QOL ) , and lifestyle variables ( physical activity , dietary intake , alcohol intake , smoking , body mass index ( BMI ) ) ] at baseline and post-intervention . RESULTS Post-intervention , 76 % of participants rated the program as excellent , 100 % rated the health coach as excellent , and 75 % rated the h and book as excellent . In addition , 80 % said that CanChange addressed their issues , 72 % said that CanChange helped them deal more effectively with their problems , and 100 % said that CanChange made them more motivated to make positive life changes . Finally , all participants said that they would recommend CanChange to other CRC survivors . From baseline to post-intervention we observed : non-significant improvements in all CRC-specific symptoms and QOL ; a significant decrease in processed meat intake [ median ( interquartile range ) : 1.0 ( 3.0 ) vs 0.0 ( 1.0 ) , p=0.01 ] ; as well as non-significant improvements in sedentary behaviour , and the proportion of participants meeting the national guidelines for fruit and vegetable intake . We observed no change in smoking status , while the results for alcohol intake , physical activity , and BMI were variable . CONCLUSIONS CanChange was a feasible and potentially effective lifestyle intervention to improve health outcomes for CRC survivors . A large r and omised controlled trial will follow to test the longer-term effects of this approach Background : This report examines the outcome data for Project PREVENT , a two-site r and omized control trial design ed to reduce behavioral risk factors for colorectal cancer among individuals who have been diagnosed with adenomatous colon polyps . Methods : The study sample included 1,247 patients with recent diagnosis of adenomatous colorectal polyps . Within 4 weeks following the polypectomy , participants completed a baseline survey by telephone , and were r and omized to either Usual Care ( UC ) or the PREVENT intervention , which was design ed to target multiple risk factors . The intervention consisted of a telephone-delivered intervention plus tailored material s , and focused on the six primary behavioral risk factors for colorectal cancer , including red meat consumption , fruit and vegetable intake , multivitamin intake , alcohol , smoking , and physical inactivity . Results : Participation in the PREVENT intervention was associated with a significantly greater reduction in prevalence of multiple risk factors for colorectal cancer compared with UC . Only about one third of UC participants dropped any risk factors during the study period , compared with almost half of the PREVENT participants . PREVENT participants were also significantly more likely to change more than one behavior than UC participants . Conclusions : The PREVENT intervention was effective in helping patients change multiple risk factors . These results provide further support that more comprehensive interventions that move beyond emphasis on a single risk factor are acceptable to patient population s , can result in improvements , and are cost effective OBJECTIVES We analyzed outcomes from a study that examined social- context ual factors in cancer prevention interventions for working class , multiethnic population s. METHODS Ten community health centers were r and omized to intervention or to control . Patients who resided in low-income , multiethnic neighborhoods were eligible ; the intervention targeted fruit and vegetable consumption , red meat consumption , multivitamin intake , and physical activity . Outcomes were measured at 8 months . RESULTS The intervention led to significant increases in fruit and vegetable consumption and multivitamin intake and reductions in red meat consumption ; no change was found in physical activity levels . The intervention effect was not changed when context ual variables that may function as confounders or effect modifiers ( e.g. , gender , education , race/ethnicity , respondent and parents ' country of birth , and poverty status ) were included in the analyses . CONCLUSIONS The intervention led to significant improvements in health behaviors among a working class , multiethnic population , regardless of race/ ethnicity and socioeconomic status . Interventions that respond to the social context of working class individuals across racial/ethnic categories hold promise for improving cancer-related risk behaviors BACKGROUND The Cochrane Collaboration is strongly encouraging the use of a newly developed tool , the Cochrane Collaboration Risk of Bias Tool ( CCRBT ) , for all review groups . However , the psychometric properties of this tool to date have yet to be described . Thus , the objective of this study was to add information about psychometric properties of the CCRBT including inter-rater reliability and concurrent validity , in comparison with the Effective Public Health Practice Project Quality Assessment Tool ( EPHPP ) . METHODS Both tools were used to assess the method ological quality of 20 r and omized controlled trials included in our systematic review of the effectiveness of knowledge translation interventions to improve the management of cancer pain . Each study assessment was completed independently by two review ers using each tool . We analysed the inter-rater reliability of each tool 's individual domains , as well as final grade assigned to each study . RESULTS The EPHPP had fair inter-rater agreement for individual domains and excellent agreement for the final grade . In contrast , the CCRBT had slight inter-rater agreement for individual domains and fair inter-rater agreement for final grade . Of interest , no agreement between the two tools was evident in their final grade assigned to each study . Although both tools were developed to assess ' quality of the evidence ' , they appear to measure different constructs . CONCLUSIONS Both tools performed quite differently when evaluating the risk of bias or method ological quality of studies in knowledge translation interventions for cancer pain . The newly introduced CCRBT assigned these studies a higher risk of bias . Its psychometric properties need to be more thoroughly vali date d , in a range of research fields , to underst and fully how to interpret results from its application OBJECTIVES To assess the effect of a nutrition education intervention on nutritional factors and oxidative stress during treatment of breast cancer . DESIGN Nonr and omized clinical trial conducted in 2010 - 2011 , including an evaluation at baseline and after 12 months . PARTICIPANTS Women from Brazil who had breast cancer , divided into an intervention group ( Output:	Self-monitoring interventions and individual lifestyle counselling led to , or were associated with reduced meat consumption . Providing information about the health or environmental consequences of eating meat was associated with reduced intentions to consume and select meat in virtual environments , but there was no evidence to suggest this approach influenced actual behaviour . Education about the animal welfare consequences of eating meat was associated with reduced intentions to consume meat , while interventions implicitly highlighting animal suffering were not . Education on multiple consequences of eating meat led to mixed results . Tailored education was not found to reduce actual or intended meat consumption , though few studies assessed this approach . ConclusionS ome interventions targeting conscious determinants of human behaviour have the potential to reduce the dem and for meat . In particular , self-monitoring interventions and individual lifestyle counselling can help to reduce meat consumption . There was evidence of effectiveness of some educational messages in reducing intended consumption and selection of meat in virtual environments .
MS2779	*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 early results in patients with incision lines closed only along the skin and subcutaneous tissue after removal of the great saphenous vein during coronary artery bypass surgery . Material s and Methods : We enrolled 82 patients who underwent elective operations in our clinic between December 2008 and April 2009 . The patients had similar demographic characteristics , and the method of incision closure was chosen r and omly . Three patients were excluded due to in-hospital mortality . The saphenous incision lines were closed using continuous skin sutures in 41 patients ( Group 1 ) or using continuous subcutaneous sutures followed by continuous skin sutures in 38 patients ( Group 2 ) . Patients were followed every day that they were in the hospital , in the first week after being discharged , and at the end of the second month after discharge . The incision lines were evaluated for hematomas , infection , edema , pain and numbness . Results : During the follow-up performed in-hospital and in the first week after discharge , infection , edema and numbness were observed significantly more often in Group 2 than in Group 1 . Hematoma was observed more often in Group 1 , and pain was observed more often in Group 2 , but neither of these findings reached statistical significance . During the follow-up at the end of the second month after discharge , infection , edema , and numbness were observed significantly more frequently in Group 2 . Conclusion : In patients undergoing saphenous removal using st and ard procedures , it is sufficient to close the incision line using only skin sutures OBJECTIVE This study was undertaken to determine the most appropriate management of the subcutaneous tissue of midline vertical incisions with 3 cm or more of subcutaneous fat . STUDY DESIGN Patients undergoing surgery within the Division of Gynecologic Oncology at University of South Florida and East Tennessee State University with 3 cm or more of subcutaneous fat were r and omly assigned to 1 of 3 groups : suture approximation of Camper 's fascia , closed suction drainage of the subcutaneous space , or no intervention as a control group . Participants were evaluated daily during postoperative hospitalization and at 2 and 6 weeks postoperatively as an outpatient . Demographic information , perioperative data , and wound complications were recorded and then analyzed with chi2 , t test , analysis of variance , and logistic regression where appropriate . RESULTS Two hundred twenty-five patients were enrolled with 222 eligible for evaluation . Wound complications were observed in 34 ( 15.3 % ) patients , and 25 of these women also had wound disruption . Overall wound complication and wound disruption rates were not significantly different between groups : suture ( 12.8 % , 7.7 % ) , drain ( 17.9 % , 14.9 % ) , control ( 15.6 % , 11.7 % ) ; P = .70 and P = .39 , respectively . CONCLUSION Suture approximation or drainage of the subcutaneous tissues of women with 3 cm or more subcutaneous fat measured in midline vertical incisions result ed in no significant change in the incidence of overall wound complications or superficial wound disruption OBJECTIVE The aim of this study was to determine the effect of the depth of subcutaneous tissue at the operative site and the closure of subcutaneous tissue on abdominal wound disruption after cesarean delivery . METHODS 164 women divided into two groups : 70 with subcutaneous tissue thickness of at least 2 cm and 94 with subcutaneous tissue thickness more than 2 cm . These groups were r and omized to closure of the subcutaneous fat tissue or no closure with cesarean delivery . RESULTS In the 68 women with subcutaneous tissue thickness of at least 2 cm who completed the study , there was no difference between closure and no closure subgroups in terms of incidence of wound disruption . In 91 women with subcutaneous tissue thickness more than 2 cm who completed the study , the incidence of wound disruption was significantly higher in the no closure subgroup . In the no closure subgroup of 91 women with subcutaneous fat thickness more than 2 cm , the incidence of wound disruption was significantly higher than that of the 68 women with subcutaneous tissue thickness at least 2 cm . CONCLUSIONS Subcutaneous tissue approximation with absorbable suture at closure of the abdominal incision during cesarean delivery appears to reduce the rate of postoperative wound disruption in patients with more than 2 cm of subcutaneous tissue Background : The objective of this study was to compare the cosmetic outcome of facial lacerations closed with a single or double layer of sutures . Methods : Patients aged 1 year or older presenting to a university-based emergency department with nongaping ( width , < 10 mm ) , simple , nonbite , facial lacerations were r and omized to closure with a single layer of simple interrupted 6 - 0 polypropylene sutures or a double layer of simple interrupted 6 - 0 polypropylene plus inverted deep dermal 5 - 0 polyglactin sutures . At 90 days , the scar width and cosmetic appearance were determined using a vali date d 100-mm visual analogue scale ranging from 0 ( worst ) to 100 ( best ) and a vali date d wound evaluation score ranging from 0 ( worst ) to 6 ( best ) . Results : Sixty-five patients were r and omized to single-layer ( n = 32 ) or double-layer ( n = 33 ) closure . Mean age ( SD ) was 18.5 years ( 20.0 ) , and 14 percent were female . Groups were similar in baseline patient and wound characteristics . Length of single-layer closure was 7 minutes shorter ( 95 percent CI , 2 to 11 minutes ) than double-layer closure . There were no infections or dehiscences in either group . There were no between-group differences in patient ( mean difference , 0.5 mm ; 95 percent CI , –5.7 to 6.6 mm ) or practitioner ( mean difference , 1.0 mm ; 95 percent CI , –4.8 to 6.7 mm ) visual analogue scale scores . All but one patient had an optimal wound evaluation score of 6 ( p = not significant ) . Scar width was similar at 90 days ( mean difference , 0.2 mm ; 95 percent CI , –0.05 to 0.5 ) . Conclusions : Single-layer closure of nongaping , minor ( <3 cm ) facial lacerations is faster than double-layer closure . Cosmetic outcome and scar width are similar in sutured wounds whether or not deep dermal sutures are used Purpose : The aim of this prospect i ve r and omized study was to investigate the necessity of suturing subcutaneous fat tissue in elective abdominal surgery . Methods : 415 patients undergoing elective abdominal surgery were admitted to the trial . The patients were divided into two basic groups according to wound contamination : clean operations ( n = 201 ) and clean-contaminated operation ( n = 214 ) . Subcutaneous suturing of the subcutaneous fat tissue was performed in half of the patients in each group , determined using the envelope method ( ‘ Suture Yes ’ or ‘ Suture No ’ ) . Wounds were checked on postoperative days 3 , 7 , 14 , and 30 . Infectious and non-infectious wound complications were charted in the records . Data were statistically analyzed . The percentages of complications in groups with and without subcutaneous suturing were statistically compared using Yates ’ corrected χ2 two-tailed test . Results : There were no statistically significant group differences in infectious and non-infectious wound complications . Conclusion : These results suggest that omission of subcutaneous fat tissue suturing does not increase the occurrence of infectious or non-infectious wound complications Purpose Surgical site infections ( SSI ) cause excess morbidity and mortality in modern surgery . Several different approaches to reduce the incidence of SSI have been investigated with variable results . Method This is to our knowledge the first systematic r and omized evaluation in patients undergoing laparotomy in visceral surgery to clarify whether widely used subcutaneous drains ( Redon ) affect wound infection as the primary outcome measure . Results In 200 patients , we were unable to show a statistically significant impact on the postoperative healing process in patients with the full variety of abdominal surgical interventions . Overall , we observed surgical site infection in 9.5 % of all patients ( n = 19 ) , of these n = 9 ( 47.4 % ) were in the control group without a drain , and 10 ( 52.6 % ) were in the experimental group with a Redon drain ( not significant ) . Conclusion As this study could not demonstrate a reduction of SSI by the use of Redon drains , there is no indication for prophylactic subcutaneous suction drains after laparotomy AIMS To evaluate the role of subcutaneous tissue closure in relation to wound disruption after abdominal hysterectomy in obese patients . MATERIAL AND METHODS In a prospect i ve study at a tertiary referral centre in Mumbai , India , 60 obese patients with subcutaneous fat more than 2.5 cms were included in the study . In 30 patients , subcutaneous tissue was closed using synthetic suture ( dexon ) while in 30 control patients subcutaneous tissue was not closed . Average weight in the study and control groups were 69 -/+ 9.2 kg and 63.3 -/+ 11.2 kg respectively . RESULTS The wound disruption occurred in 5 patients in non-closure group as compared to only one in the closure group . Incidence of seroma , haematoma formation and other wound complications were higher in the non-closure group . CONCLUSIONS Closure of the subcutaneous tissue after abdominal hysterectomy of women with at least 2.5 cms of subcutaneous tissue lowers the overall rate of complications leading to disruption of the incision Methods for combining data from several studies exist and appear to be quite useful . None satisfactorily addresses the question of what studies should be combined . This issue is the most serious method ological limitation . Even studies with statistically significant interaction might still be combined if the effect were in the same direction . Thus , substantial scientific input is required as to what criteria must be met by each potential study . Much can be learned from combining or pooling data but it must be done cautiously . Pooling exercises do not replace well design ed prospect i ve clinical trials . Efforts for establishing basic design criteria to allow for multicentre and multicountry trials to be more easily combined might be useful . BACKGROUND Wound infection and dehiscence are both major contributors to postoperative morbidity . One potential cause or co-factor is the use of suture material . A recently introduced subcutaneous suture is coated with triclosan ( TC ) , an antiseptic drug . It is suggested to reduce wound complications . METHODS To investigate the effect of TC on wound healing a double blind prospect i ve pilot study in women undergoing a breast reduction was performed . Each patient was her own control . After r and omisation the TC-coated sutures were used either on the left or right side . The contralateral side was used as the control . The incidence of dehiscence was studied . RESULTS Twenty-six patients were included . In the TC breasts there was a wound dehiscence in 16 cases , whereas in the control breasts in seven cases a dehiscence was observed ( P=0.023 ) . CONCLUSION These results suggest that TC-coated sutures should be used with caution . These sutures have already been introduced on to the market without good clinical studies and might have potential adverse effects as shown by these data Wound haematoma is an undesirable complication of surgery . We report a prospect i ve trial to establish whether a subcutaneous fat stitch affects haematoma formation in hip surgery . A series of 50 patients undergoing hip surgery were r and omised to have either a fat stitch or no fat stitch during wound closure . The wounds were assessed clinical ly with a minimum follow-up of 5 weeks . Subcutaneous haematomas were seen more easily with the patient st and ing . As clinical assessment for haematoma formation may be unreliable , each patient also had an ultrasound scan . Although the incidence of subcutaneous haematoma was slightly higher in the no fat stitch group ( 36 % compared with 24 % in the fat stitch group ) this difference was not statistically significant ( chi 2 test , P < 0.5 ) . There were no significant differences in the incidence of wound infection and healing rate . From our study we also showed that ultrasound examination was twice as sensitive as clinical examination in diagnosing subcutaneous haematomas and that subcutaneous haematomas are common after hip surgery We report a prospect i ve trial to establish whether a subcutaneous fat stitch reduces the incidence of haematoma formation , infection and wound dehiscence following saphenous vein excision for coronary revascularization . Two groups of patients undergoing coronary revascularization were studied . In the first group of 100 patients the saphenous vein was harvested from both legs . Legs were r and omized to have either a fat stitch or no fat stitch during wound closure . By using both legs of each patient we eliminated the effect of general factors on wound healing , thus the patients acted as their own controls . In the second group of 200 patients , the saphenous vein was harvested from the thigh , and patients r and omly allocated to either a fat stitch or no fat stitch during wound closure . The wounds were examined daily for 7 days , and again after 6 weeks at the follow-up . There was no difference in the rate of wound complication in the fat stitch groups ( 9 % ) compared with the no fat stitch groups ( 8 % ) , however , the fat stitch groups required more surgical intervention for skin edge necrosis . It appears that closure of the subcutaneous fat following saphenectomy is unnecessary , and may be detrimental to skin healing Objective . The aim of the study was to evaluate the impact of an Output:	There is currently evidence of very low quality which is insufficient to support or refute subcutaneous closure after non-caesarean operations . The use of subcutaneous closure has the potential to affect patient outcomes and utilisation of healthcare re sources .
MS2780	*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 Identifying true therapeutic progress in patients with acute myeloid leukemia ( AML ) requires a comparison of treatment strategies and results on the basis of uniform patient selection . To foster comparability across five clinical studies , we introduced a common st and ard arm combined with a general upfront r and omization and performed prospect i ve analyses with adjustment for differences in prognostic baseline characteristics . PATIENTS AND METHODS Whereas the studies ' own regimens differed in chemotherapies , risk adaption , and guidelines for allogeneic stem-cell transplantation , the st and ard arm contained uniform cytarabine- and anthracycline-based st and ard-dose remission induction and high-dose consolidation courses . RESULTS Of 2,995 evaluable patients aged 16 to 60 years , 290 patients were r and omly assigned to the common st and ard arm . Seventy percent of the 290 achieved complete remissions ( 62 % with complete recovery , 8 % with incomplete recovery ; 95 % CI , 65 % to 76 % ) . Five-year survival probabilities were 44.3 % ( 95 % CI , 37.7 % to 50.7 % ) for overall survival , 44.8 % ( 95 % CI , 37.0 % to 52.2 % ) for relapse-free survival , and 31.5 % ( 95 % CI , 25.7 % to 37.4 % ) for event-free survival . Neither the unadjusted survival probabilities of the Kaplan-Meier method nor their adjustment for prognostic variables in multiple Cox regression models led to statistically significant different results in the three survival end points when the outcomes of each study were compared with the st and ard arm . CONCLUSION A strictly prospect i ve comparison of different treatment strategies in patients with AML did not show clinical ly relevant outcome differences when compared through a common st and ard treatment arm . The results provide a representative basis for further therapeutic approaches The optimal induction for older adults with acute myeloid leukemia ( AML ) is unknown . Several anthracyclines have been proposed , but the data remain equivocal . Additionally , few prospect i ve trials of priming with hematopoietic growth factors to cycle leukemia cells prior to induction chemotherapy have been conducted . Three hundred and sixty-two older adults with previously untreated AML were r and omized to either daunorubicin , idarubicin or mitoxantrone with a st and ard dose of cytarabine as induction therapy . In addition , 245 patients were also r and omized to receive granulocyte-macrophage colony-stimulating factor ( GM-CSF ) or placebo beginning 2 days prior to induction chemotherapy and continuing until marrow aplasia . No difference was observed in the disease-free overall survival or in toxicity among patients receiving any of the 3 induction regimens or among those receiving growth factor or placebo for priming . However , the complete remission rate for the first 113 analyzable patients , who did not participate in the priming study and started induction therapy 3 to 5 days earlier than those who did , was significantly higher ( 50 % versus 38 % ; P = .03 ) . None of the anthracyclines is associated with improved outcome in older adults . Priming with hematopoietic growth factor did not improve response when compared with placebo . Furthermore , delaying induction therapy in older adults may lead to a lower complete remission rate The first EORTC ( European Organization of Research and Treatment of Cancer ) acute myeloblastic leukemia ( AML ) pilot study ( 58872 ) was conducted between January 1988 and December 1991 . Out of 108 patients , 78 % achieved complete remission ( CR ) , and event-free survival ( EFS ) and survival rates ( s.e . , % ) at 7 years were 40 ( 5 ) and 51 % ( 6 % ) , respectively . It indicated that mitoxantrone could be substituted for conventional anthracyclines in the treatment of childhood AML without inducing cardiotoxicity . The aim of the next EORTC 58921 trial was to compare the efficacy and toxicity of idarubicin vs mitoxantrone in initial chemotherapy courses , further therapy consisting of allogeneic bone marrow transplantation ( alloBMT ) in patients with an HLA-compatible sibling donor or chemotherapy in patients without a donor . Out of 177 patients , recruited between October 1992 and December 2002 , 81 % reached CR . Overall 7-year EFS and survival rates were 49 ( 4 ) and 62 % ( 4 % ) , respectively . Out of 145 patients who received the first intensification , 39 had a sibling donor . In patients with or without a donor , the 7-year disease-free survival ( DFS ) rate was 63 ( 8) and 57 % ( 5 % ) and the 7-year survival rate was 78 ( 7 ) and 65 % ( 5 % ) , respectively . Patients with favorable , intermediate and unfavorable cytogenetic features had a 5-year EFS rate of 57 , 45 and 45 % and a 5-year survival rate of 89 , 67 and 53 % , respectively CCG-2961 incorporated 3 new agents , idarubicin , fludarabine and interleukin-2 , into a phase 3 AML trial using intensive-timing remission induction/consolidation and related donor marrow transplantation or high-dose cytarabine intensification . Among 901 patients under age 21 years , 5-year survival was 52 % , and event-free survival was 42 % . Survival improved from 44 % between 1996 and 1998 to 58 % between 2000 and 2002 ( P = .005 ) , and treatment-related mortality declined from 19 % to 12 % ( P = .025 ) . Partial replacement of daunomycin with idarubicin in the 5-drug induction combination achieved a remission rate of 88 % , similar to historical controls . Postremission survival was 56 % in patients r and omized to either 5-drug reinduction or fludarabine/cytarabine/idarubicin . For patients with or without a related donor , respective 5-year disease-free survival was 61 % and 50 % ( P = .021 ) ; respective survival was 68 % and 62 % ( P = .425 ) . Donor availability conferred no benefit on those with inv(16 ) or t(8;21 ) cytogenetics . After cytarabine intensification , patients r and omized to interleukin-2 or none experienced similar outcomes . Factors predictive of inferior survival were age more than 16 years , non-white ethnicity , absence of related donor , obesity , white blood cell count more than 100 000 x 10(9)/L , -7/7q- , -5/5q- , and /or complex karyotype . No new agent improved outcomes ; experience may have contributed to better results time PURPOSE To compare the antitumor efficacy of three different anthracyclines in combination with cytarabine and etoposide in adult patients with newly diagnosed acute myeloid leukemia ( AML ) . PATIENTS AND METHODS We r and omly assigned 2,157 patients ( age range , 15 to 60 years ) to receive intensive induction-consolidation chemotherapy containing either daunorubicin , idarubicin , or mitoxantrone . After achieving complete remission ( CR ) , patients were assigned to undergo either allogeneic or autologous stem-cell transplantation ( SCT ) , depending on the availability of a sibling donor . RESULTS The overall CR rate ( 69 % ) was similar in the three groups . Autologous SCT was performed in 37 % of cases in the daunorubicin arm versus only 29 % and 31 % in mitoxantrone and idarubicin , respectively ( P < .001 ) . However , the disease-free survival ( DFS ) and survival from CR were significantly shorter in the daunorubicin arm : the 5-year DFS was 29 % versus 37 % and 37 % in mitoxantrone and idarubicin , respectively . The proportion of patients who underwent allogeneic SCT ( 22 % ) was equivalent in the three treatment groups , and the outcome was similar as well . The [ corrected ] 5-year overall survival rates were 31 % , 34 % , and 34 % , [ corrected ] respectively . CONCLUSION In adult patients with AML who do not receive an allogeneic SCT , the use of mitoxantrone or idarubicin instead of daunorubicin enhances the long-term efficacy of chemotherapy BACKGROUND A complete remission is essential for prolonging survival in patients with acute myeloid leukemia ( AML ) . Daunorubicin is a cornerstone of the induction regimen , but the optimal dose is unknown . In older patients , it is usual to give daunorubicin at a dose of 45 to 50 mg per square meter of body-surface area . METHODS Patients in whom AML or high-risk refractory anemia had been newly diagnosed and who were 60 to 83 years of age ( median , 67 ) were r and omly assigned to receive cytarabine , at a dose of 200 mg per square meter by continuous infusion for 7 days , plus daunorubicin for 3 days , either at the conventional dose of 45 mg per square meter ( 411 patients ) or at an escalated dose of 90 mg per square meter ( 402 patients ) ; this treatment was followed by a second cycle of cytarabine at a dose of 1000 mg per square meter every 12 hours [ DOSAGE ERROR CORRECTED ] for 6 days . The primary end point was event-free survival . RESULTS The complete remission rates were 64 % in the group that received the escalated dose of daunorubicin and 54 % in the group that received the conventional dose ( P=0.002 ) ; the rates of remission after the first cycle of induction treatment were 52 % and 35 % , respectively ( P<0.001 ) . There was no significant difference between the two groups in the incidence of hematologic toxic effects , 30-day mortality ( 11 % and 12 % in the two groups , respectively ) , or the incidence of moderate , severe , or life-threatening adverse events ( P=0.08 ) . Survival end points in the two groups did not differ significantly overall , but patients in the escalated-treatment group who were 60 to 65 years of age , as compared with the patients in the same age group who received the conventional dose , had higher rates of complete remission ( 73 % vs. 51 % ) , event-free survival ( 29 % vs. 14 % ) , and overall survival ( 38 % vs. 23 % ) . CONCLUSIONS In patients with AML who are older than 60 years of age , escalation of the dose of daunorubicin to twice the conventional dose , with the entire dose administered in the first induction cycle , effects a more rapid response and a higher response rate than does the conventional dose , without additional toxic effects . ( Current Controlled Trials number , IS RCT N77039377 ; and Netherl and s National Trial Register number , NTR212 . Between 1990 and 1996 , we conducted a r and omized trial in adults with newly diagnosed acute myeloid leukemia ( AML ) in order to compare relapse-free interval ( RFI ) after double induction ( arm B ) , timed-sequential induction ( arm C ) , or control " 3 + 7 " induction ( arm A ) . Patients achieving complete remission ( CR ) after induction + /- salvage received the same consolidation chemotherapy , which included a dosage stratification according to patient 's age ( younger or older than 50 years ) . This long-term analysis was performed in 592 patients ( arm A/B/C , 197/198/197 patients ) . Overall CR rate was 76 % without differences between the 3 arms , even if a salvage course was less frequently needed in arm B. Treatment-related mortality , either during the induction or the postremission phase , was not significantly higher in arms B and C than in arm A. Among the 449 CR patients , 250 relapsed ( arm A/B/C , 90/87/73 patients ) without significant differences in RFI in arms B and C versus arm A ( P = .39 and .15 , by the Gray test ) . However , when analyzing the 345 patients younger than 50 , RFI was significantly improved in younger patients receiving timed-sequential induction ( P = .038 by the Gray test ) , while not in those receiving double induction . Event-free survival and overall survival were similar in the 3 r and omization arms PURPOSE In patients with acute myeloid leukemia ( AML ) , induction chemotherapy is based on st and ard doses of anthracyclines and cytarabine . High doses of cytarabine have been reported as being too toxic for patients older than age 50 years , but few studies have evaluated intensified doses of anthracyclines . PATIENTS AND METHODS In this r and omized Acute Leukemia French Association 9801 ( ALFA-9801 ) study , high doses of daunorubicin ( DNR ; 80 mg/m(2)/d x 3 days ) or idarubicin ( ID Output:	Neither study reported on QoL. AUTHORS ' CONCLUSIONS Compared with DNR in induction therapy of newly diagnosed AML , IDA prolongs OS and DFS , increases CR rate and reduces relapse rate , although increases the risks of death on induction therapy and grade 3/4 mucositis . The currently available evidence does not show any difference between IDA and MIT used in induction therapy of newly diagnosed AML . Additionally , there is no evidence for difference on the effect of IDA compared with DNR , MIT , DOX or ZRB on
MS2781	*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 effects of goldenseal ( Hydrastis canadensis ) and kava kava ( Piper methysticum ) supplementation on human CYP3A activity were evaluated using midazolam ( MDZ ) as a phenotypic probe . Sixteen healthy volunteers were r and omly assigned to receive either goldenseal or kava kava for 14 days . Each supplementation phase was followed by a 30‐day washout period . MDZ ( 8 mg , per os ) was administered before and after each phase , and pharmacokinetic parameters were determined using st and ard non‐compartmental methods . Comparisons of pre‐ and post‐supplementation MDZ pharmacokinetic parameters revealed significant inhibition of CYP3A by goldenseal ( AUC(0–∞ ) , 107.9±43.3 vs 175.3±74.8 ng·h/ml ; Cl/F/kg , 1.26±0.59 vs 0.81±0.45 l/h/kg ; T1/2 , 2.01±0.42 vs 3.15±1.12 h ; Cmax , 50.6±26.9 vs 71.2±50.5 ng/ml ) . MDZ disposition was not affected by kava kava supplementation . These findings suggest that significant herb – drug interactions may result from the concomitant ingestion of goldenseal and CYP3A substrates Phytochemical‐mediated modulation of cytochrome P450 ( CYP ) activity may underlie many herb‐drug interactions . Single‐time point phenotypic metabolic ratios were used to determine whether long‐term supplementation of Citrus aurantium , Echinacea purpurea , milk thistle ( Silybum marianum ) , or saw palmetto ( Serenoa repens ) extracts affected CYP1A2 , CYP2D6 , CYP2E1 , or CYP3A4 activity Phytochemical-mediated modulation of P-glycoprotein ( P-gp ) and other drug transporters may give rise to many herb-drug interactions . Serial plasma concentration-time profiles of the P-gp substrate , digoxin , were used to determine whether supplementation with goldenseal or kava kava modified P-gp activity in vivo . Twenty healthy volunteers were r and omly assigned to receive a st and ardized goldenseal ( 3210 mg daily ) or kava kava ( 1227 mg daily ) supplement for 14 days , followed by a 30-day washout period . Subjects were also r and omized to receive rifampin ( 600 mg daily , 7 days ) and clarithromycin ( 1000 mg daily , 7 days ) as positive controls for P-gp induction and inhibition , respectively . Digoxin ( Lanoxin , 0.5 mg ) was administered p.o . before and at the end of each supplementation and control period . Serial digoxin plasma concentrations were obtained over 24 h and analyzed by chemiluminescent immunoassay . Comparisons of area under the curve (AUC)(0–3 ) , AUC(0–24 ) , Cmax , CL/F , and elimination half-life were used to assess the effects of goldenseal , kava kava , rifampin , and clarithromycin on digoxin pharmacokinetics . Rifampin produced significant reductions ( p < 0.01 ) in AUC(0–3 ) , AUC(0–24 ) , CL/F , t1/2 , and Cmax , whereas clarithromycin increased these parameters significantly ( p < 0.01 ) . With the exception of goldenseal 's effect on Cmax ( 14 % increase ) , no statistically significant effects on digoxin pharmacokinetics were observed following supplementation with either goldenseal or kava kava . When compared with rifampin and clarithromycin , supplementation with these specific formulations of goldenseal or kava kava did not appear to affect digoxin pharmacokinetics , suggesting that these supplements are not potent modulators of P-gp in vivo The effects of berberine ( BBR ) on the pharmacokinetics of ciclosporin A ( CsA ) were examined in healthy volunteers . Six healthy male volunteers were orally treated with 0.3 g BBR , twice daily for 10 days . Pharmacokinetic investigations on CsA at 6 mg/kg were done both before and at the end of the BBR treatment period . Another six healthy male volunteers were involved in the pharmacokinetic study with 3 mg CsA/kg , in which the subjects orally received the second single dose of 3 mg CsA/kg , followed by a single oral dose of 0.3 g BBR . The blood CsA concentrations were determined by fluorescence polarization immunoassay . In the pharmacokinetic study with 6 mg CsA/kg , BBR caused no significant changes in the pharmacokinetic parameters of CsA. However , in the trial with 3 mg CsA/kg , the average percentage increase in area under the blood concentration-time curve of CsA was 19.2 % ( P < 0.05 ) and the mean C12 increased to 123 microg/l from 104 microg/l ( P < 0.05 ) , without altering elimination half-life ( t(1/2 ) ) , maximum blood drug concentration ( Cmax ) , time to Cmax ( tmax ) , apparent oral clearance ( CL/F ) . The present results suggest that BBR can increase the oral bioavailability of CsA at the dosage of 3 mg/kg . The BBR-mediated increase in CsA bioavailability may be partly attributed to a decrease in liver and /or intestinal metabolism through the inhibition of CYP3A4 in the liver and /or gut wall . The BBR-induced increase in emptying time of stomach and small intestine might be another reason for the increase in CsA bioavailability . However , the speculation should be proved by further investigation Phytochemical-mediated modulation of P-glycoprotein ( P-gp ) and other drug transporters may underlie many herb-drug interactions . Serial serum concentration-time profiles of the P-gp substrate , digoxin , were used to determine whether supplementation with milk thistle or black cohosh modified P-gp activity in vivo . Sixteen healthy volunteers were r and omly assigned to receive a st and ardized milk thistle ( 900 mg daily ) or black cohosh ( 40 mg daily ) supplement for 14 days , followed by a 30-day washout period . Subjects were also r and omized to receive rifampin ( 600 mg daily , 7 days ) and clarithromycin ( 1000 mg daily , 7 days ) as positive controls for P-gp induction and inhibition , respectively . Digoxin ( Lanoxicaps , 0.4 mg ) was administered orally before and at the end of each supplementation and control period . Serial digoxin serum concentrations were obtained over 24 h and analyzed by chemiluminescent immunoassay . Comparisons of area under the serum concentration time curves from 0 to 3 h ( AUC(0–3 ) ) , AUC(0–24 ) , Cmax , apparent oral clearance of digoxin ( CL/F ) , and elimination half-life were used to assess the effects of milk thistle , black cohosh , rifampin , and clarithromycin on digoxin pharmacokinetics . Rifampin produced significant reductions ( p < 0.01 ) in AUC(0–3 ) , AUC(0–24 ) , and Cmax , whereas clarithromycin increased these parameters significantly ( p < 0.01 ) . Significant changes in digoxin half-life and CL/F were also observed with clarithromycin . No statistically significant effects on digoxin pharmacokinetics were observed following supplementation with either milk thistle or black cohosh , although digoxin AUC(0–3 ) and AUC(0–24 ) approached significance ( p = 0.06 ) following milk thistle administration . When compared with rifampin and clarithromycin , supplementation with these specific formulations of milk thistle or black cohosh did not appear to affect digoxin pharmacokinetics , suggesting that these supplements are not potent modulators of P-gp in vivo Phytochemical‐mediated modulation of cytochrome P450 ( CYP ) activity may underlie many herb‐drug interactions . Single‐time point phenotypic metabolic ratios were used to determine whether long‐term supplementation of goldenseal ( Hydrastis canadensis ) , black cohosh ( Cimicifuga racemosa ) , kava kava ( Piper methysticum ) , or valerian ( Valeriana officinalis ) extracts affected CYP1A2 , CYP2D6 , CYP2E1 , or CYP3A4/5 activity Purpose We assessed the human in vivo metabolic drug interaction profile of Ginkgo biloba extract EGb 761 ® with respect to the activities of major cytochrome P450 ( CYP ) enzymes . Methods A single-center , open-label , r and omized , three-fold crossover , cocktail phenotyping design was applied . In r and om order , the following treatments were administered to 18 healthy men and women for 8 days each : placebo twice daily , EGb 761 ® 120 mg twice daily , and EGb 761 ® 240 mg in the morning and placebo in the evening . In the morning of day 8 , administration was performed together with the orally administered phenotyping cocktail ( enzyme , metric ) : 150 mg caffeine ( CYP1A2 , paraxanthine/caffeine plasma ratio 6-h postdose ) , 125 mg tolbutamide ( CYP2C9 , plasma concentration 24-h postdose ) , 20 mg omeprazole ( CYP2C19 , omeprazole/5-hydroxy omeprazole plasma ratio 3-h postdose ) , 30 mg dextromethorphan ( CYP2D6 , dextromethorphan/dextrorphan plasma ratio 3-h postdose ) , and 2 mg of midazolam ( CYP3A , plasma concentration 6-h postdose ) . Formally , absence of a relevant interaction was assumed if the 90 % confidence intervals ( CIs ) for EGb 761 ® /placebo ratios of the metrics were within the 0.70–1.43 range . Results EGb 761 ® /placebo ratios for phenotyping metrics were close to unity for all CYPs . Furthermore , respective CIs were within the specified margins for all ratios except CYP2C19 for EGb 761 ® 120 mg twice daily ( 90 % CI 0.681–1.122 ) and for CYP2D6 for EGb 761 ® 240 mg once daily ( 90 % CI 0.667–1.281 ) . These findings were attributed to the intraindividual variability of the metrics used . All treatments were well tolerated . Conclusion EGb 761 ® has no relevant effect on the in vivo activity of the major CYP enzymes in humans and therefore has no relevant potential to cause respective metabolic drug – drug interactions BACKGROUND & AIMS Ginkgo biloba extract ( EGb 761 ) has been shown to ameliorate some defects associated with the insulin resistance syndrome and so patients with Type 2 diabetes mellitus ( T2DM ) may be inclined to co-ingest the herb with their medications , such as metformin . This study was design ed to determine if the co-ingestion of EGb 761 and metformin would alter the pharmacokinetic properties of metformin in T2DM patients and persons without diabetes , who may ingest it for other purpose s. METHOD Normal glucose tolerance ( NGT ) subjects ( n=10 ; age , 39.2+/-14.0 years ; fasting plasma glucose ( FPG ) , 90+/-7 mg/dl ; body mass index ( BMI ) , 24.1+/-3.7 kg/m(2 ) ) and 10 T2DM patients ( n=10 ; age , 51.7+/-8.9 years ; FPG , 150+/-7 mg/dl ; BMI , 33.7+/-5.7 kg/m(2 ) ) completed a r and omized , double-blind , placebo-controlled crossover study . They ingested either EGb 761 ( 12 0mg/day as a single dose ) or a vegetable-based placebo during each arm for 3 months . At the end of each arm , the NGT subject ingested a single 500 mg dose of metformin ( non-diabetics ) and the T2DM subject took his/her prescribed metformin dose ( 250 - 850 mg ) with 120 mg EGb 761 . Blood and urine sample s were collected over an 8-h period , and in the case of T2DM subjects , additionally over the first 2h of the subsequent 3 days . RESULTS Ingestion of EGb 761 produced no significant changes in diagnostic laboratory tests in either group , except reducing glycosylated hemoglobin A(1c ) levels ( from 7.7+/-1.2 to 7.2+/-0.9 % , P<0.05 ) in T2DM the Output:	Collectively , the available evidence indicates that , at commonly recommended doses , none of these herbs act as potent or moderate inhibitors or inducers of cytochrome P450 ( CYP ) enzymes or P-glycoprotein ( ABCB1 ) . Weak effects in terms of either induction or inhibition were found for GB ( presystemic/hepatic CYP3A4 induction/inhibition , CYP2C19 induction at high doses ) , milk thistle/silymarin ( CYP2C9 inhibition ) , GS/berberine ( CYP3A4 and CYP2D6 inhibition ) , Echinacea ( presystemic/hepatic CYP3A4 inhibition/induction , CYP1A2 and CYP2C9 inhibition at high doses ) . Information was found not always complete for the major drug metabolizing CYP enzymes in the less well-studied herbs and is largely limited to P-glycoprotein ( ABCB1 ) when effects on drug transporters have been investigated
MS2782	*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 : Transmuscular tubular diskectomy has been introduced to increase the rate of recovery , although evidence is lacking . OBJECTIVE : To evaluate the 2-year results of tubular diskectomy compared with conventional microdiskectomy . METHODS : Three hundred twenty-eight patients with persistent leg pain caused by lumbar disk herniation were r and omly assigned to undergo tubular diskectomy ( 167 patients ) or conventional microdiskectomy ( 161 patients ) . Main outcome measures were scores from Rol and -Morris Disability Question naire for Sciatica , Visual Analog Scale for leg pain and low-back pain , and Likert self-rating scale of global perceived recovery . RESULTS : On the basis of intention-to-treat analysis , there was no significant difference between tubular diskectomy and conventional microdiskectomy in Rol and -Morris Disability Question naire for Sciatica scores during 2 years after surgery ( between-group mean difference [ Δ ] = 0.6 ; 95 % confidence interval [ CI ] , −0.3 - 1.6 ) . Patients treated with tubular diskectomy reported more leg pain ( Δ = 3.3 mm ; 95 % CI , 0.2 - 6.2 ) and more low-back pain ( Δ = 3.0 mm ; 95 % CI , −0.2 - 6.3 ) than those patients treated with conventional microdiskectomy . At 2 years , 71 % of patients assigned to tubular diskectomy documented a good recovery vs 77 % of patients assigned to conventional microdiskectomy ( odds ratio , 0.76 ; 95 % CI , 0.45 - 1.28 ; P = .35 ) . Repeated surgery rates within 2 years after tubular diskectomy and conventional microdiskectomy were 15 % and 10 % , respectively ( P = .22 ) . CONCLUSION : Tubular diskectomy and conventional microdiskectomy result ed in similar functional and clinical outcomes . Patients treated with tubular diskectomy reported more leg pain and low-back pain , although the differences were small and not clinical ly relevant Objective Percutaneous endoscopic lumbar discectomy ( PELD ) and microdiscectomy with the microscope endoscopic tubular retractor system(METRx-MD ) are considered popular minimally invasive surgery ( MIS ) methods for the treatment of lumbar disc herniation . Many authors have also reported good clinical outcomes of these methods , but there are few comparative studies of them . This report compares the clinical outcomes of PELD and METRx-MD for lumbar disc herniation as MIS methods and discusses the efficacy of PELD . Methods Seventy-two patients who had undergone single-level unilateral discectomy using two different methods , PELD and METRx-MD , between 2009 and 2011 were given a follow-up examination prospect ively . Thirty-seven of these patients underwent discectomy using PELD , and the remaining 35 patients underwent discectomy using METRx-MD . In addition to the general parameters , clinical outcomes were assessed as specific parameters using the Visual Analogue Scale ( VAS ) score , the Oswestry Disability Index ( ODI ) , the Short-form 36 ( SF-36 ) , and the return-to-work time . Results Sixty-seven percent ( 25/37 ) of the patients in the PELD group and 74%(26/35 ) in the METRx-MD group were included in follow-up more than 6 months post-operatively . The mean improvements in the VAS scores for the back pain , leg pain , and ODI were 2.6 , 4.8 , and 30.1 % for the PELD group and 2.8 , 4.6 , and 33.2 % for the METRx-MD group , respectively . The SF-36 physical health component subscale score improved from 40.6 pre-operatively to 68.3 at the last follow-up for the PELD group post-operatively , and from 48.5 to 65.1 in the mental component subscale ( METRx-MD group : from 34.4 to 66.5 and from 44.87 to 56.7 ) . Complications occurred in 3/37 patients in the PELD group and in 2/35 patients in the METRx-MD group in the peri-operative period . The mean return-to-work times were 37.5 days in the PELD group and 42.5 days in the METRx-MD group . Conclusion The outcomes for the PELD group are comparable to those for the METRx-MD group . It can thus be concluded that PELD for lumbar disk herniations may be performed safely and effectively . Also , PELD can be considered one of the treatment modalities of lumbar disk herniation Background : Highly migrated intracanal disk herniation is not among the exclusion criteria of the interlaminar microendoscopic diskectomy ( MED ) procedure . The goal of this prospect i ve , r and omized , controlled study was to compare the effect of the size of the skin incision and the method of h and ling the multifidus muscle on the results of the interlaminar MED procedure versus conventional microdiskectomy in retrieving highly migrated intracanal disk herniations . Methods : Seventy-three patients with highly migrated intracanal lumbar disk herniations treated with either minimal incision , multifidus-sparing MED or conventional microdiskectomy were observed for 2 years . Primary ( clinical ) outcomes data included the results of the Numerical Rating Scale ( NRS ) for back and leg pain and the Oswestry Disability Index ( ODI ) to quantify pain and disability , respectively . Secondary objective outcomes data included surgical time , blood loss , postoperative analgesics , length of hospital stay , time to return to work , the rates of revision surgery complications , and the results of the patient satisfaction index ( PSI ) and the modified MacNab criteria . Results : At final follow-up , relief of leg pain was statistically significant for both groups . NRS back pain , ODI , PSI , and the modified MacNab criteria showed no improvement in the conventional microdiskectomy group . Secondary outcomes data in the MED group were significantly better than those for the control group . Conclusions : Highly migrated intracanal lumbar disk herniations can be sufficiently retrieved using minimal incision , multifidus-sparing MED , which is an effective alternative to conventional microdiskectomy . The minimal skin incision and multifidus-sparing approach of the MED had a positive effect on clinical outcomes , which were stable throughout the 2-year follow-up period . Level of Evidence : Therapeutic level In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias Study Design . Prospect i ve , r and omized , controlled study of patients with lumbar disc herniations , operated either in a full-endoscopic or microsurgical technique . Objective . Comparison of results of lumbar discectomies in full-endoscopic interlaminar and transforaminal technique with the conventional microsurgical technique . Summary of Background Data . Even with good results , conventional disc operations may result in subsequent damage due to trauma . Endoscopic techniques have become the st and ard in many areas because of the advantages they offer intraoperatively and after surgery . With the transforaminal and interlaminar techniques , 2 full-endoscopic procedures are available for lumbar disc operations . Methods . One hundred seventy-eight patients with full-endoscopic or microsurgical discectomy underwent follow-up for 2 years . In addition to general and specific parameters , the following measuring instruments were used : VAS , German version North American Spine Society Instrument , Oswestry Low-Back Pain Disability Question naire . Results . After surgery 82 % of the patients no longer had leg pain , and 14 % had occasional pain . The clinical results were the same in both groups . The recurrence rate was 6.2 % with no difference between the groups . The full-endoscopic techniques brought significant advantages in the following areas : back pain , rehabilitation , complications , and traumatization . Conclusion . The clinical results of the full-endoscopic technique are equal to those of the microsurgical technique . At the same time , there are advantages in the operation technique and reduced traumatization . With the surgical devices and the possibility of selecting an interlaminar or posterolateral to lateral transforaminal procedure , lumbar disc herniations outside and insidethe spinal canal can be sufficiently removed using the full-endoscopic technique , when taking the appropriate criteria into account . Full-endoscopic surgery is a sufficient and safe supplementation and alternative to microsurgical procedures OBJECTIVE Minimal access surgery as a less invasive alternative to st and ard macro- and microsurgical approaches is becoming increasingly popular in the management of traumatic and degenerative spine diseases . However , data is lacking if minimal access spine surgery is indeed beneficial . This prospect i ve r and omized study was conducted to compare efficiency , safety , and outcome of st and ard open microsurgical discectomy ( SOMD ) for lumbar disc herniation with microsurgical discectomy using an 11.5 mm trocar system for minimal access to the spine . METHODS Sixty patients were r and omized to two groups of 30 patients each . Group 1 was treated by SOMD , and Group 2 was treated by minimal access microsurgical discectomy ( MAMD ) . Perioperative parameters and pre- and postoperative clinical findings including sensory or motor deficits and pain according to the visual analog scale , Oswestry Disability Index scores , and Short Form-36 results were assessed . All patients were followed for at least 6 months postoperatively ( mean , 16 mo ) . RESULTS Preoperatively , no statistically significant intergroup differences could be detected proving the comparability of both groups . Postoperatively , significant improvement of neurological symptoms and pain as measured by the visual analog scale , Oswestry Disability Index , and Short Form-36 scores could be achieved in both groups . In regard to operative time , intraoperative blood loss , and complication rate , slightly better results were observed in the MAMD group . CONCLUSIONS OMD and MAMD allow achievement of significant improvement of pain and neurological deficits in patients with lumbar disc herniations . Differences in operative time , blood loss , and complication rates were statistically not significant in MAMD compared with SOMD , indicating that , at least in lumbar disc surgery , minimal access trocar techniques are a viable alternative to st and ard spinal approaches Background : Intervertebral disc herniation is a major cause of low back pain . Several treatment methods are available for lumbar disc herniation including Chemonucleolysis , open surgery , nucleoplasty , laser disc decompression , and intradiscal electrothermal therapy . The high prevalence of lumbar disc herniation necessitates a minimally invasive yet effective treatment method . In this study , we compared the outcomes of open surgery and nucleoplasty method in patients with single lumbar disc herniation . Material s and Methods : This study was a noninferiority r and omized clinical trial conducted in one of the University Hospitals of Isfahan Medical University ; The Alzahra Hospital . About 200 patients with the diagnosis of lumbar disc herniation were recruited and were assigned to either the treatment or control groups using block r and omization . One group received open surgery and the other group received nucleoplasty as the method of treatment . Patients were revisited at 14 days , 1 , 2 , 3 months , and 1-year after surgery and were assessed for the following variables : Lower back pain , lower limb pain , common complications of surgery ( e.g. , discitis , infection and hematoma ) and recurrence of herniation . Results : The mean ( st and ard deviation ) severity of low back pain was reduced from 6.92 ( 2.5 ) to 3.43 ( 2.3 ) in the nucleoplasty group ( P = 0.04 ) and from 7.5 ( 2.2 ) to 3.04 ( 1.61 ) in the discectomy group ( P = 0.73 ) . Between group difference was not statistically significant ( P = 0.44 ) , however , time and treatment interaction was significant ( P = 0.001 ) . The level of radicular pain evaluated 1 year after treatment was reduced from 8.1 ( 1.2 ) to 2.9 ( 1.2 ) ( P = 0.004 ) and from 7.89 ( 2.1 ) to 3.6 ( 2.5 ) ( P = 0.04 ) in the discectomy and the nucleoplasty groups respectively , significant interaction between time and treatment options was observed ( P < 0.001 ) while there was no significant difference between two treatment groups ( P = 0.82 ) . Conclusion : Our results show that while nucleoplasty is as effective as open discectomy in the treatment of lumbar disc herniation , it is also less invasive with higher patient compliance . T Output:	Compared with the OD/MD , results of this meta- analysis suggest that PELD has a lower risk of overall complications and a lower risk of complications necessitating conservative treatment .
MS2783	*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 Preliminary evidence suggests that meditative exercise may have benefits for patients with chronic systolic heart failure ( HF ) ; this has not been rigorously tested in a large clinical sample . We sought to investigate whether tai chi , as an adjunct to st and ard care , improves functional capacity and quality of life in patients with HF . METHODS A single-blind , multisite , parallel-group , r and omized controlled trial evaluated 100 out patients with systolic HF ( New York Heart Association class I-III , left ventricular ejection fraction ≤40 % ) who were recruited between May 1 , 2005 , and September 30 , 2008 . A group-based 12-week tai chi exercise program ( n = 50 ) or time-matched education ( n = 50 , control group ) was conducted . Outcome measures included exercise capacity ( 6- minute walk test and peak oxygen uptake ) and disease-specific quality of life ( Minnesota Living With Heart Failure Question naire ) . RESULTS Mean ( SD ) age of patients was 67 ( 11 ) years ; baseline values were left ventricular ejection fraction , 29 % ( 8 % ) and peak oxygen uptake , 13.5 mL/kg/min ; the median New York Heart Association class of HF was class II . At completion of the study , there were no significant differences in change in 6-minute walk distance and peak oxygen uptake ( median change [ first quartile , third quartile ] , 35 [ -2 , 51 ] vs 2 [ -7 , 54 ] meters , P = .95 ; and 1.1 [ -1.1 , 1.5 ] vs -0.5 [ -1.2 , 1.8 ] mL/kg/min , P = .81 ) when comparing tai chi and control groups ; however , patients in the tai chi group had greater improvements in quality of life ( Minnesota Living With Heart Failure Question naire , -19 [ -23 , -3 ] vs 1 [ -16 , 3 ] , P = .02 ) . Improvements with tai chi were also seen in exercise self-efficacy ( Cardiac Exercise Self-efficacy Instrument , 0.1 [ 0.1 , 0.6 ] vs -0.3 [ -0.5 , 0.2 ] , P < .001 ) and mood ( Profile of Mood States total mood disturbance , -6 [ -17 , 1 ] vs -1 [ -13 , 10 ] , P = .01 ) . CONCLUSION Tai chi exercise may improve quality of life , mood , and exercise self-efficacy in patients with HF . Trial Registration clinical trials.gov Identifier : NCT00110227 Objectives : To study the effect of unsupported upper limb and lower limb exercise training and their combined influence on the exercise performance and health-related quality of life in COPD patients . Material s and Methods : Thirty patients were r and omly assigned to one of the three groups , through block r and omization . Of the three groups , group A received upper limb training , group B received lower limb training , and group C received both upper and lower limb training . Patients in group A , B , and C underwent exercise training five times a week for four weeks . The outcome measures used in the study were unsupported upper limb endurance test ( UULEX ) , Six-Minute Walk Test ( 6-MWT ) , and a Chronic Respiratory Question naire . Statistical analysis was performed with analysis of variance , Wilcoxon scale , and a Kruskal Wallis one way ANOVA test , and a P value of .05 was used in the study . Conclusion : The combined upper limb and lower limb training group showed a significant improvement in the exercise performance and health-related quality of life BACKGROUND Although the benefits of exercise on the health of patients with chronic obstructive pulmonary disease ( COPD ) have been widely reported , the effect of Tai Chi as an alternative exercise has not been thoroughly evaluated in patients with COPD . This study reported a r and omised controlled trial , which investigated the effects of Tai Chi on lung function , exercise capacity , and diaphragm strength in patients with COPD . TRIAL DESIGN Single blind r and omised controlled study . SETTING Department of Respiratory Medicine , Xiangya Hospital , Central South University . METHODS Forty patients with COPD were r and omised into either a control group or Tai Chi intervention group . Participants in the control group received only routine care , while participants in the Tai Chi group received routine care and completed a six-month Tai Chi exercise program . OUTCOMES Lung function parameters , blood gas parameters , 6-min walking distance ( 6MWD ) , and diaphragm strength parameters . RESULTS Lung function parameters ( FEV1 : 1.43 ± 0.08 and FEV1 ( % ) predicted : 47.6 ± 4.76 ) , 6MWD ( 476 ± 15 ) and diaphragm strength parameters ( TwPes : 1.17 ± 0.07 , TwPga : -1.12 ± 0.06 , and TwPdi : 1.81 ± 0.09 ) were found to be significantly increased in participants who successfully completed the six-month Tai Chi program compared to participants in the control group who only received routine care ( p<0.05 ) . These parameters were also found to be significantly increased in participants who completed the Tai Chi exercise program compared to the baseline ( p<0.05 ) . In contrast , no significant differences in PaO2 and PaCO2 were observed in participants before or after completing a Tai Chi program or between Tai Chi group and control group ( p>0.05 ) . CONCLUSIONS Tai Chi enhances lung function , exercise capacity , and diaphragm strength . However , this is only preliminary research data and a larger trial is needed for more detailed results OBJECTIVE To determine the feasibility of a r and omized controlled trial of the effect of a tai chi program on quality of life and exercise capacity in patients with COPD . METHODS We r and omized 10 patients with moderate to severe COPD to 12 weeks of tai chi plus usual care ( n = 5 ) or usual care alone ( n = 5 ) . The tai chi training consisted of a 1-hour class , twice weekly , that emphasized gentle movement , relaxation , meditation , and breathing techniques . Exploratory outcomes included disease-specific symptoms and quality -of-life , exercise capacity , pulmonary function tests , mood , and self-efficacy . We also conducted qualitative interviews to capture patient narratives regarding their experience with tai chi . RESULTS The patients were willing to be r and omized . Among 4 of the 5 patients in the intervention group , adherence to the study protocol was excellent . The cohort 's baseline mean ± SD age , percent-of-predicted FEV₁ , and ratio of FEV₁ to forced vital capacity were 66 ± 6 y , 50 ± 12 % , and 0.63 ± 0.14 , respectively . At 12 weeks there was significant improvement in Chronic Respiratory Question naire score among the tai chi participants ( 1.4 ± 1.1 ) , compared to the usual-care group ( -0.1 ± 0.4 ) ( P = .03 ) . There were nonsignificant trends toward improvement in 6-min walk distance ( 55 ± 47 vs -13 ± 64 m , P = .09 ) , Center for Epidemiologic Studies Depression Scale ( -9.0 ± 9.1 vs -2.8 ± 4.3 , P = .20 ) , and University of California , San Diego Shortness of Breath score ( -7.8 ± 3.5 vs -1.2 ± 11 , P = .40 ) . There were no significant changes in either group 's peak oxygen uptake . CONCLUSIONS A r and omized controlled trial of tai chi is feasible in patients with moderate to severe COPD . Tai chi exercise as an adjunct to st and ard care warrants further investigation BACKGROUND Patients with Parkinson 's disease have substantially impaired balance , leading to diminished functional ability and an increased risk of falling . Although exercise is routinely encouraged by health care providers , few programs have been proven effective . METHODS We conducted a r and omized , controlled trial to determine whether a tailored tai chi program could improve postural control in patients with idiopathic Parkinson 's disease . We r and omly assigned 195 patients with stage 1 to 4 disease on the Hoehn and Yahr staging scale ( which ranges from 1 to 5 , with higher stages indicating more severe disease ) to one of three groups : tai chi , resistance training , or stretching . The patients participated in 60-minute exercise sessions twice weekly for 24 weeks . The primary outcomes were changes from baseline in the limits-of-stability test ( maximum excursion and directional control ; range , 0 to 100 % ) . Secondary outcomes included measures of gait and strength , scores on functional-reach and timed up- and -go tests , motor scores on the Unified Parkinson 's Disease Rating Scale , and number of falls . RESULTS The tai chi group performed consistently better than the resistance-training and stretching groups in maximum excursion ( between-group difference in the change from baseline , 5.55 percentage points ; 95 % confidence interval [ CI ] , 1.12 to 9.97 ; and 11.98 percentage points ; 95 % CI , 7.21 to 16.74 , respectively ) and in directional control ( 10.45 percentage points ; 95 % CI , 3.89 to 17.00 ; and 11.38 percentage points ; 95 % CI , 5.50 to 17.27 , respectively ) . The tai chi group also performed better than the stretching group in all secondary outcomes and outperformed the resistance-training group in stride length and functional reach . Tai chi lowered the incidence of falls as compared with stretching but not as compared with resistance training . The effects of tai chi training were maintained at 3 months after the intervention . No serious adverse events were observed . CONCLUSIONS Tai chi training appears to reduce balance impairments in patients with mild-to-moderate Parkinson 's disease , with additional benefits of improved functional capacity and reduced falls . ( Funded by the National Institute of Neurological Disorders and Stroke ; Clinical Trials.gov number , NCT00611481 . ) The aims of the study were to determine the effect of short-form Sun-style t’ai chi ( SSTC ) ( part A ) and investigate exercise intensity of SSTC ( part B ) in people with chronic obstructive pulmonary disease ( COPD ) . Part A : after confirmation of eligibility , participants were r and omly allocated to either the t’ai chi group or control group ( usual medical care ) . Participants in the t’ai chi group trained twice weekly for 12 weeks . Part B : participants who had completed training in the t’ai chi group performed a peak exercise test ( incremental shuttle walk test ) and SSTC while oxygen consumption ( VO2 ) was measured . Exercise intensity of SSTC was determined by the per cent of VO2 reserve . Of 42 participants ( mean±sd forced expiratory volume in 1 s 59±16 % predicted ) , 38 completed part A and 15 completed part B. Compared to control , SSTC significantly increased endurance shuttle walk time ( mean difference 384 s , 95 % CI 186–510 ) ; reduced medial-lateral body sway in semi-t and em st and ( mean difference -12.4 mm , 95 % CI -21– -3 ) ; and increased total score on the chronic respiratory disease question naire ( mean difference 11 points , 95 % CI 4–18 ) . The exercise intensity of SSTC was 53±18 % of VO2 reserve . SSTC was an effective training modality in people with COPD achieving a moderate exercise intensity which meets the training recommendations Our aim was to determine the minimal important difference ( MID ) for 6-min walk distance ( 6MWD ) and maximal cycle exercise capacity ( MCEC ) in patients with severe chronic obstructive pulmonary disease ( COPD ) . 1,218 patients enrolled in the National Emphysema Treatment Trial completed exercise tests before and after 4–6 weeks of pre-trial rehabilitation , and 6 months after r and omisation to surgery or medical care . The St George 's Respiratory Question naire ( domain and total scores ) and University of California San Diego Shortness of Breath Question naire ( total score ) served as anchors for anchor-based MID estimates . In order to calculate distribution-based estimates , we used the st and ard error of measurement , Cohen 's effect size and the empirical rule effect size . Anchor-based estimates for the 6MWD were 18.9 m ( 95 % CI 18.1–20.1 m ) , 24.2 m ( 95 % CI 23.4–25.4 m ) , 24.6 m ( 95 % CI 23.4–25.7 m ) and 26.4 m ( 95 % CI 25.4–27.4 m ) , which were similar to distribution-based MID estimates of 25.7 , 26.8 and 30.6 m. For MCEC , anchor-based estimates for the MID were 2.2 W ( 95 % CI 2.0–2.4 W ) , 3.2 W ( 95 % CI 3.0–3.4 W ) , 3.2 W ( 95 % CI 3.0–3.4 W ) and 3.3 W ( 95 % CI 3.0–3.5 W ) , while distribution-based estimates were 5.3 and 5.5 W. We suggest a MID of 26±2 m for 6MWD and 4±1 W for MCEC for patients with severe COPD BACKGROUND Exercise tolerance is an important clinical aspect of chronic obstructive pulmonary disease that can be easily and reli Output:	CONCLUSION Preliminary evidence suggests that Tai Chi has beneficial effects on exercise capacity and HRQoL in COPD patients . This exercise can be recommended as an effective alternative training modality in pulmonary rehabilitation programs .
MS2784	*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 Tonsillectomy has been described using a number of techniques . Recently Coblation Technology has been used to remove tonsils with anecdotal evidence of a reduction in post-operative morbidity . In this study we aim to see if there is any difference in post-operative pain , tonsillar fossae healing and return to a normal diet performing tonsillectomy , using tissue coblation compared with st and ard bipolar dissection . METHODS A double blind r and omised control trial to compare the technique of tissue coblation with st and ard bipolar dissection to remove tonsils in 38 children on the waiting list for tonsillectomy , with a history of chronic tonsillitis or obstructive tonsils . RESULTS A significant reduction in post-operative pain was found in the children whose tonsils were removed by tissue coblation ( P<0.0001 ) . More rapid healing of the tonsillar fossae was found in the coblation group . Children who had their tonsils removed by coblation were found to return to their normal diet far sooner than those who underwent bipolar dissection . There were no episodes of primary or secondary haemorrhage in either group . CONCLUSIONS This new technique using tissue coblation for tonsil removal offers significant advantages in the post-operative period , with rapid return to a normal diet and a drastic reduction in analgesic requirements following the surgery Objectives : The purpose of this study was to establish if children experienced any difference in pain , between coblation tonsillectomy and coblation tonsillotomy OBJECTIVES : The objective of this study was to compare the safety , difficulty of removal , and postoperative pain profile of radiofrequency ablation versus st and ard electrocautery removal of tonsils . STUDY DESIGN AND SETTING : A prospect i ve , blinded study was design ed to remove 1 tonsil with each of the 2 methods . Time of operation , estimated blood loss , difficulty of operation , postoperative pain , rate of postoperative hemorrhage , and the patient 's preferred technique were evaluated . RESULTS : The operating time was significantly longer ( P < 0.007 ) and the patients reported significantly less pain ( P < 0.001 ) with radiofrequency ablation . There were no differences in blood loss , difficulty of operation , or postoperative hemorrhage rates . The patients preferred the radiofrequency ablation technique ( P < 0.001 ) . CONCLUSION : Radiofrequency ablation is a viable method to remove tonsillar tissue . Operating time for this procedure will likely decrease with experience . There was significantly less pain reported with radiofrequency ablation compared with st and ard electrocautery . ( Otolaryngol Head Neck Surg 2004;130:300–5 . Tonsillectomy has been performed by a number of techniques . This double blind r and omized controlled study compares the technique of tissue coblation with bipolar dissection for the removal of tonsils in 10 adult patients with a history of chronic tonsillitis . A significant reduction in post-operative pain and more rapid healing of the tonsillar fossae were found in the side removed by tissue coblation . There were no episodes of primary or secondary haemorrhage on either side . This new technique for tonsil removal warrants further study OBJECTIVE To determine the efficacy of intracapsular tonsillectomy using low-temperature plasma excision for improving the quality of the postoperative experience and for treating obstructive symptoms through 12 months postoperatively . DESIGN Prospect i ve , r and omized , controlled , single-blind study . SETTING Multiple private or institutional otolaryngology clinics . PATIENTS Fifty-five children ( aged 3 - 12 years ) with obstructive tonsillar hypertrophy . INTERVENTION Patients were r and omly assigned and blinded to undergo either intracapsular tonsillectomy using low-temperature plasma excision ( n = 27 ) or total tonsillectomy using conventional electrosurgery ( n = 28 ) . MAIN OUTCOME MEASURES Operative data , 14-day recovery variables , and obstructive symptoms were prospect ively collected through 12 months . RESULTS During the first 14 days , significantly fewer children in the intracapsular group reported nausea ( P = .01 ) or lost weight ( P = .003 ) . The intracapsular group had a significantly faster resolution of pain ( P = .01 ) , had an earlier return to a normal diet ( P = .004 ) , ceased taking pain medication sooner ( P = .002 ) , and returned to normal activity sooner ( P = .04 ) . Postoperatively , the intracapsular group had more residual tonsil tissue than the total tonsillectomy group ( P = .002 for the 3- and 12-month visits ) . However , the incidence of recurring obstructive symptoms , pharyngitis , and antibiotic use was similar in both treatment groups during the 12 months . CONCLUSIONS Postoperative morbidity normally associated with traditional ( total ) tonsillectomy was significantly reduced after intracapsular tonsillectomy using low-temperature plasma excision . The residual tonsillar tissue associated with this technique was of no clinical consequence Coblation tonsillectomy has shown promising results with respect to postoperative pain when compared with other techniques . Our study was design ed to compare this technique with bipolar scissor tonsillectomy . Forty adult patients with a history of chronic or recurrent tonsillitis referred for st and ard tonsillectomy were recruited and r and omized into two groups . Twenty were operated with Coblator and 20 with bipolar scissors . Exclusion criteria were a history of quinsy , bleeding disorder , or any major health problems . All participants completed the study . Postoperative pain , return to normal diet , and estimated need for sick leave were utilized as parameters . Data on operative time , difficulty of tissue removal , and hemostasis were also analyzed . Operative time was longer ( P < 0.001 ) and tissue removal as well as hemostasis control were more difficult ( P = 0.005 , P = 0.013 ) with Coblator than with bipolar scissors . Participants in Coblator group assessed higher pain scores 1 and 3 h postoperatively ( P = 0.044 , P = 0.036 ) . From the time of extubation , patients had access to an opioid ( fentanyl ) via a self-controlled analgesia device . The number of doses of analgesics needed during the hospital stay was significantly higher in the Coblator group ( P = 0.020 ) . During the 14-day follow-up , no significant differences were found in pain scores , return to solid food or subjective working ability between the groups . Considering the overall outcome of the patients the results did not favor coblation technique over bipolar scissors BACKGROUND Quantum molecular resonance coagulation is an innovative technology that uses molecular resonance to cut and coagulate precisely , cleanly , and hemostatically at low tissue temperature levels . This technology offers a new possibility for tonsillectomy . OBJECTIVES To compare molecular resonance ( MRT ) with coblation ( CAT ) devices for pediatric tonsillectomy . STUDY DESIGN Prospect i ve , two-group , r and omized trial in a tertiary care pediatric institution . One hundred fifty-seven children for whom tonsillectomy was indicated were r and omly assigned to receive MRT ( n = 79 ) or CAT ( n = 78 ) . Main outcome measures included intraoperative time , blood loss , postoperative pain , and weight loss . Histopathologic examination was performed on all excised tonsils . Patients , parents , and pathologist were blinded to surgical modality . RESULTS Histopathologic evaluation revealed significantly reduced thermal injury with MRT than with CAT ( 43 microns vs. 126 , respectively , P < .001 ) , and was statistically associated with reduced muscular , blood vessel , and nerve fiber damage . No intraoperative blood loss was observed in patients following MRT . Statistically significant reduced pain scores were related to the MRT ( P < .002 ) . In addition , the MRT method showed a quick return to normal diet with even weight gain during the 10-day postoperative period . One child in the CAT group experienced delayed bleeding and required readmission . CONCLUSIONS Molecular resonance for pediatric tonsillectomy result ed in significantly reduced histopathologic thermal injury and lower pain scores compared with coblation . Further studies are advised to support these data OBJECTIVE : To compare the postoperative recovery of patients who undergo intracapsular to subcapsular Coblation tonsillectomy . STUDY DESIGN AND SETTING : This was a prospect i ve , r and omized , double-blinded study . A total of 69 children , aged 2 to 16 years , were r and omized to intracapsular ( n = 34 ) or subcapsular ( n = 35 ) tonsillectomy . The Coblation technique was used with both groups . Outcomes measures were assessed on postoperative day 1 or 2 and 5 or 6 . These included child and parental rating of pain with the Wong Faces pain scale , analgesic use , oral intake , and activity level . RESULTS : Intracapsular tonsillectomy patients had similar levels of pain to subcapsular tonsillectomy patients on day 1 or 2 . However , at day 5 or 6 , intracapsular tonsillectomy patients had significantly less pain than the subcapsular tonsillectomy patients . Intracapsular patients ate more and were more active at both time points . CONCLUSION AND SIGNIFICANCE : Children with obstructive sleep apnea who undergo tonsillectomy demonstrate better postoperative recovery after intracapsular tonsillectomy . The intracapsular versus subcapsular difference may be best appreciated at a delayed time point ( day 5 or 6 ) rather than early ( day 1 or 2 ) OBJECTIVE To compare plasma-mediated ablation ( PMA ) with monopolar electrosurgery ( MES ) for pediatric tonsillectomy . DESIGN Prospect i ve , r and omized , blinded study . SETTING Academic children 's hospital . PARTICIPANTS Thirty-four children , aged 4 to 7 years . INTERVENTIONS Tonsillectomy by means of PMA ( n = 17 ) or MES ( n = 17 ) . OUTCOME MEASURES We measured surgical efficacy , estimated blood loss , and surgical time during tonsillectomy and morphine use , immediate postoperative pain , and recovery scores after tonsillectomy . Parents recorded recovery of normal diet and activity and their own return to work for 10 days after surgery . Histopathologic evaluation of excised tonsils was performed . We review ed medical records and attempted follow-up telephone contact . RESULTS With no significant difference in blood loss compared with MES , PMA was effective for tonsillectomy . Performance of PMA took longer ( 24 vs 16 minutes ; P = .002 ) . Results of histopathologic evaluation showed less thermal injury with PMA than with MES ( P = .03 ) . Morphine consumption , pain , and recovery scores were equivalent between groups . We found no significant difference in recovery of normal diet and activity or parental return to work . Patients undergoing PMA had a greater number of perioperative complications than those undergoing MES , including 2 patients in the PMA group ( compared with none in the MES group ) who required unplanned admission for postoperative airway obstruction . CONCLUSIONS Plasma-mediated ablation for pediatric tonsillectomy result ed in less histopathologic thermal injury than MES , but did not show a statistically faster recovery to normal activity and diet or parental return to work . In addition , PMA took longer to perform , and had more complications . Therefore , PMA should not replace MES for pediatric tonsillectomy . The reduced thermal injury with PMA supports investigation into other means of using plasma ablation to treat tonsillar hypertrophy OBJECTIVES To determine if the coblation tonsillectomy ( subcapsular dissection ) results in less postoperative pain , equivalent intraoperative blood loss , equivalent postoperative hemorrhage rates , and faster healing compared with tonsillectomy was performed using unipolar electrocautery in adult patients . STUDY DESIGN The authors conducted a prospect i ve clinical trial . METHODS Forty-eight patients underwent tonsillectomy and were r and omly assigned to have one tonsil removed with coblation and the other with unipolar electrocautery . Outcome measures included time to remove each tonsil , intraoperative blood loss , patient-reported pain , postoperative hemorrhage , and amount of healing 2 weeks after surgery . RESULTS Mean time to remove a single tonsil with coblation and electrocautery was 8.22 minutes and 6.33 minutes , respectively ( P = .011 ) . Mean intraoperative blood loss for each technique was less than 10 mL. Postoperative pain was significantly less with coblation as compared with electrocautery : 18.6 % less painful during the first week of recovery . Seventy percent of blinded patients identified the coblation side as less painful during the overall 14-day convalescent period . Postoperative hemorrhage rates ( 2.1 % for coblation and 6.2 % for electrocautery ) were not significantly different . No difference in tonsillar fossa healing was observed between the two techniques 2 weeks after surgery . During nine of the 48 surgeries , wires on the tip of the coblation h and piece experienced thinning to the point of discontinuity while removing a single tonsil . CONCLUSIONS Coblation subcapsular tonsillectomy was less painful than electrocautery tonsillectomy in this 48-patient group . On average , intraoperative blood loss was less than 10 mL for both techniques . Postoperative hemorrhage rates and the degree of tonsillar fossa healing were similar between the two techniques . The coblation h and piece experienced degradation of vital wires in 18 % of cases necessitating the use of a second , new h and piece Objectives : The aim of this study was to compare postoperative symptoms Output:	The overall hemorrhage rate of 4.1 % found in this meta- analysis shows that coblation is a safe and effective technique for tonsillectomies with a secondary bleeding rate similar to what is reported for comparable techniques such as bipolar diathermia
MS2785	*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 Laparoscopic surgery as an alternative to open surgery in patients with rectal cancer has not yet been shown to be oncologically safe . The aim in the COlorectal cancer Laparoscopic or Open Resection ( COLOR II ) trial was to compare laparoscopic and open surgery in patients with rectal cancer . METHODS A non-inferiority phase 3 trial was undertaken at 30 centres and hospitals in eight countries . Patients ( aged ≥18 years ) with rectal cancer within 15 cm from the anal verge without evidence of distant metastases were r and omly assigned to either laparoscopic or open surgery in a 2:1 ratio , stratified by centre , location of tumour , and preoperative radiotherapy . The study was not masked . Secondary ( short-term ) outcomes -including operative findings , complications , mortality , and results at pathological examination-are reported here . Analysis was by modified intention to treat , excluding those patients with post-r and omisation exclusion criteria and for whom data were not available . This study is registered with Clinical Trials.gov , number NCT00297791 . FINDINGS The study was undertaken between Jan 20 , 2004 , and May 4 , 2010 . 1103 patients were r and omly assigned to the laparoscopic ( n=739 ) and open surgery groups ( n=364 ) , and 1044 were eligible for analyses ( 699 and 345 , respectively ) . Patients in the laparoscopic surgery group lost less blood than did those in the open surgery group ( median 200 mL [ IQR 100 - 400 ] vs 400 mL [ 200 - 700 ] , p<0·0001 ) ; however , laparoscopic procedures took longer ( 240 min [ 184 - 300 ] vs 188 min [ 150 - 240 ] ; p<0·0001 ) . In the laparoscopic surgery group , bowel function returned sooner ( 2·0 days [ 1·0 - 3·0 ] vs 3·0 days [ 2·0 - 4·0 ] ; p<0·0001 ) and hospital stay was shorter ( 8·0 days [ 6·0 - 13·0 ] vs 9·0 days [ 7·0 - 14·0 ] ; p=0·036 ) . Macroscopically , completeness of the resection was not different between groups ( 589 [ 88 % ] of 666 vs 303 [ 92 % ] of 331 ; p=0·250 ) . Positive circumferential resection margin ( < 2 mm ) was noted in 56 ( 10 % ) of 588 patients in the laparoscopic surgery group and 30 ( 10 % ) of 300 in the open surgery group ( p=0·850 ) . Median tumour distance to distal resection margin did not differ significantly between the groups ( 3·0 cm [ IQR 2·0 - 4·8 ] vs 3·0 cm [ 1·8 - 5·0 ] , respectively ; p=0·676 ) . In the laparoscopic and open surgery groups , morbidity ( 278 [ 40 % ] of 697 vs 128 [ 37 % ] of 345 , respectively ; p=0·424 ) and mortality ( eight [ 1 % ] of 699 vs six [ 2 % ] of 345 , respectively ; p=0·409 ) within 28 days after surgery were similar . INTERPRETATION In selected patients with rectal cancer treated by skilled surgeons , laparoscopic surgery result ed in similar safety , resection margins , and completeness of resection to that of open surgery , and recovery was improved after laparoscopic surgery . Results for the primary endpoint-locoregional recurrence-are expected by the end of 2013 . FUNDING Ethicon Endo-Surgery Europe , Swedish Cancer Foundation , West Gothia Region , Sahlgrenska University Hospital Introduction Total mesorectal excision ( TME ) is an essential component of surgical management of rectal cancer . Both open and laparoscopic TME have been proven to be oncologically safe . However , it remains a challenge to achieve complete TME with clear circumferential resections margin ( CRM ) with the conventional transabdominal approach , particularly in mid and low rectal tumours . Transanal TME ( TaTME ) was developed to improve oncological and functional outcomes of patients with mid and low rectal cancer . Methods An international , multicentre , superiority , r and omised trial was design ed to compare TaTME and conventional laparoscopic TME as the surgical treatment of mid and low rectal carcinomas . The primary endpoint is involved CRM . Secondary endpoints include completeness of mesorectum , residual mesorectum , morbidity and mortality , local recurrence , disease-free and overall survival , percentage of sphincter-saving procedures , functional outcome and quality of life . A Quality Assurance Protocol including central ised MRI review , histopathology re-evaluation , st and ardisation of surgical techniques , and monitoring and assessment of surgical quality will be conducted . Discussion The difference in involvement of CRM between the two treatment strategies is thought to be in favour of the TaTME . TaTME is therefore expected to be superior to laparoscopic TME in terms of oncological outcomes in case of mid and low rectal carcinomas Circumferential resection margin ( CRM ) appears as a new powerful prognostic factor of survival after surgery for rectal cancer . We aim ed to evaluate predictive factors of positive CRM following preoperative radiochemotherapy in a French trial . Patients with rectal cancer were r and omised in long course preoperative radiotherapy 45 Gy plus capecitabine versus 50 Gy plus capecitabine and oxaliplatin . Mesorectal excision was performed 6 weeks after treatment . Impact of clinical , pathological and surgical variables on positive CRM ( ≤1 mm ) were analysed by multivariate analysis . Of 565 r and omised patients , CRM was recorded in 390 cases and was positive in 8 % ( 30/390 ) . Patients with 50 Gy plus capecitabine and oxaliplatin had a 6 % rate of positive CRM while those treated by 45 Gy plus capecitabine had a 10 % rate ( p=0.128 ) . Three independent predictive factors of positive CRM were identified : abdominoperineal resection ( APR ) ( odds ratio OR=3.24 ; p=0.004 ) , vascular tumour invasion ( OR=2.78 ; p=0.026 ) and poor histological response ( modified Dworak 0 - 2 ) ( OR=9.01 ; p=0.003 ) . Significant predictive factors of positive CRM are related to type of surgery , especially APR , and poor histological prognostic factors . Intensification of neoadjuvant radiochemotherapy does not seem to have a major role in this study Background : The aim of the study was to evaluate quality of life ( QOL ) outcomes after colorectal surgery for cancer from a 6-month perspective at a single institution . Methods : Cohort study to prospect ively assess postoperative QOL in patients who underwent elective colorectal resection at the University Hospital Ostrava . QOL was assessed using the vali date d Short Form 36 ( SF-36v2 ™ ) question naire at fixed time points . Results : A total of 148 patients were enrolled in the study ( 83 and 65 patients underwent laparoscopic and open colorectal resection , respectively ) . Operative time was significantly longer ( 161 vs. 133 min ; p = 0.0073 ) and length of hospital stay was significantly shorter ( 10.7 vs. 13.1 days ; p = 0.0451 ) in the laparoscopic group . Overall 30-day morbidity rates were lower in the laparoscopic group , but the difference was not significant ( 27.7 vs. 33.8 % ; p = 0.2116 ) . QOL scores were comparable in both study groups before surgery ( p ≥ 0.05 ) . QOL was statistically significantly lower 2 days and 1 week after open colorectal surgery compared with laparoscopic surgery . One month and 6 months after surgery , there were no statistically significant differences between groups . Conclusion : The present study suggests a higher postoperative QOL during the first month after laparoscopic colorectal resection could be one of the benefits of laparoscopy BACKGROUND Laparoscopic resection of colorectal cancer is widely used . However , robust evidence to conclude that laparoscopic surgery and open surgery have similar outcomes in rectal cancer is lacking . A trial was design ed to compare 3-year rates of cancer recurrence in the pelvic or perineal area ( locoregional recurrence ) and survival after laparoscopic and open resection of rectal cancer . METHODS In this international trial conducted in 30 hospitals , we r and omly assigned patients with a solitary adenocarcinoma of the rectum within 15 cm of the anal verge , not invading adjacent tissues , and without distant metastases to undergo either laparoscopic or open surgery in a 2:1 ratio . The primary end point was locoregional recurrence 3 years after the index surgery . Secondary end points included disease-free and overall survival . RESULTS A total of 1044 patients were included ( 699 in the laparoscopic-surgery group and 345 in the open-surgery group ) . At 3 years , the locoregional recurrence rate was 5.0 % in the two groups ( difference , 0 percentage points ; 90 % confidence interval [ CI ] , -2.6 to 2.6 ) . Disease-free survival rates were 74.8 % in the laparoscopic-surgery group and 70.8 % in the open-surgery group ( difference , 4.0 percentage points ; 95 % CI , -1.9 to 9.9 ) . Overall survival rates were 86.7 % in the laparoscopic-surgery group and 83.6 % in the open-surgery group ( difference , 3.1 percentage points ; 95 % CI , -1.6 to 7.8 ) . CONCLUSIONS Laparoscopic surgery in patients with rectal cancer was associated with rates of locoregional recurrence and disease-free and overall survival similar to those for open surgery . ( Funded by Ethicon Endo-Surgery Europe and others ; COLOR II Clinical Trials.gov number , NCT00297791 . ) Purpose This study was design ed to evaluate the impact of laparoscopic rectal resection on short-term postoperative morbidity and costs . Methods A total of 168 patients with rectal cancer were r and omly assigned to laparoscopic ( n = 83 ) or open ( n = 85 ) resection . Outcome parameters were : postoperative morbidity , length of hospital stay , quality of life , long-term survival , and local recurrences . The mean follow-up period was 53.6 months . Cost-benefit analysis was based on hospital costs . Results Operative time was 53 minutes longer in the laparoscopic group ( P < 0.0001 ) . Postoperative morbidity rate was 28.9 percent in the laparoscopic vs. 40 percent in the open group ( P = 0.18 ) . The mean length of hospital stay was 10 ( 4.9 ) days in the laparoscopic group and 13.6 ( 10 ) days in the open group ( P = 0.004 ) . Local recurrence rate and five-year survival were similar in both groups ; however , the limited number of patients does not allow firm conclusions . Quality of life was better in the laparoscopic group only in the first year after surgery ( P < 0.0001 ) . The additional charge in the laparoscopic group was $ 1,748 per patient r and omized ( $ 1,194 the result of surgical instruments and $ 554 the result of longer operative time ) . The saving in the laparoscopic group was $ 1,396 per patient r and omized ( $ 647 the result of shorter length of hospital stay and $ 749 the result of the lower cost of postoperative complications ) . The net balance result ed in $ 351 extra cost per patient r and omly allocated to the laparoscopic group . Conclusions Short-term postoperative morbidity was similar in the two groups . Laparoscopic resection reduced length of hospital stay , improved first-year quality of life , and slightly increased hospital costs IMPORTANCE Evidence about the efficacy of laparoscopic resection of rectal cancer is incomplete , particularly for patients with more advanced-stage disease . OBJECTIVE To determine whether laparoscopic resection is noninferior to open resection , as determined by gross pathologic and histologic evaluation of the resected proctectomy specimen . DESIGN , SETTING , AND PARTICIPANTS A multicenter , balanced , noninferiority , r and omized trial enrolled patients between October 2008 and September 2013 . The trial was conducted by credentialed surgeons from 35 institutions in the United States and Canada . A total of 486 patients with clinical stage II or III rectal cancer within 12 cm of the anal verge were r and omized after completion of neoadjuvant therapy to laparoscopic or open resection . INTERVENTIONS St and ard laparoscopic and open approaches were performed by the credentialed surgeons . MAIN OUTCOMES AND Output:	Conclusions Laparoscopic surgery for rectal cancer is associated with similar short-term and long-term oncologic outcomes compared to open surgery . The oncologic quality of extracted specimens seems comparable regardless of the approach used
MS2786	*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 A system for screening of nutritional risk is described . It is based on the concept that nutritional support is indicated in patients who are severely ill with increased nutritional requirements , or who are severely undernourished , or who have certain degrees of severity of disease in combination with certain degrees of undernutrition . Degrees of severity of disease and undernutrition were defined as absent , mild , moderate or severe from data sets in a selected number of r and omized controlled trials ( RCTs ) and converted to a numeric score . After completion , the screening system was vali date d against all published RCTs known to us of nutritional support vs spontaneous intake to investigate whether the screening system could distinguish between trials with a positive outcome and trials with no effect on outcome . METHODS The total number of r and omized trials identified was 128 . In each trial , the group of patients was classified with respect to nutritional status and severity of disease , and it was determined whether the effect of nutritional intervention on clinical outcome was positive or absent . RESULTS Among 75 studies of patients classified as being nutritionally at-risk , 43 showed a positive effect of nutritional support on clinical outcome . Among 53 studies of patients not considered to be nutritionally at-risk , 14 showed a positive effect ( P=0.0006 ) . This corresponded to a likelihood ratio ( true positive/false positive ) of 1.7 ( 95 % CI : 2.3 - 1.2 ) . For 71 studies of parenteral nutrition , the likelihood ratio was 1.4 ( 1.9 - 1.0 ) , and for 56 studies of enteral or oral nutrition the likelihood ratio was 2.9 ( 5.9 - 1.4 ) . CONCLUSION The screening system appears to be able to distinguish between trials with a positive effect vs no effect , and it can therefore probably also identify patients who are likely to benefit from nutritional support Abstract Wasting is a major complication of advanced head and neck cancer and the aim of this study was to compare nasogastric tube feeding ( NG ) and percutaneous fluoroscopic gastrostomy ( PFG ) in these patients . The goal of these two methods of nutritional support was to improve or maintain the initial nutritional status during treatment . A total of 90 patients , all stage IV oropharynx or hypopharynx tumor , were review ed from a prospect i ve data bank . All these patients were treated by concomitant chemotherapy and twice-daily continuous radiotherapy with no acceleration . Fifty patients were managed by PFG , and the rest by NG . Mechanical failure , duration of feeding , complications , nutritonal evaluation and quality of life were analysed . Mechanical failure occurred in 32 of the 40 NG patients and in seven of the gastrostomy group . In the PFG group , 80 % of patients conserved their nutritional support after the end of the radiotherapy , none patient in the NG group . In the PFG group , two presented a wound infection and six had aspiration pneumonia while in the NG group , 21 had aspiration pneumonia probably due to the NG tube ( gastroesophageal reflux ) . The feeding methods were found to be equally effective at maintaining body weight and body mass index at time 1 ( 3 weeks ) and at time 2 ( 6 weeks ) . Advantages were associated with PFG cosmesis , mobility and quality of life . PFG is a safe and effective method of providing enteral nutrition during treatment to patients with advanced head and neck cancer and offers important advantages over NG Malnutrition occurs frequently in patients with cancer of the gastrointestinal ( GI ) or head and neck area and can lead to negative outcomes . The aim of this study is to determine the impact of early and intensive nutrition intervention ( NI ) on body weight , body composition , nutritional status , global quality of life ( QoL ) and physical function compared to usual practice in oncology out patients receiving radiotherapy to the GI or head and neck area . Out patients commencing at least 20 fractions of radiotherapy to the GI or head and neck area were r and omised to receive intensive , individualised nutrition counselling by a dietitian using a st and ard protocol and oral supplements if required , or the usual practice of the centre ( general advice and nutrition booklet ) . Outcome parameters were measured at baseline and 4 , 8 and 12 weeks after commencing radiotherapy using valid and reliable tools . A total of 60 patients ( 51 M : 9F ; mean age 61.9±14.0 years ) were r and omised to receive either NI ( n=29 ) or usual care ( UC ) ( n=31 ) . The NI group had statistically smaller deteriorations in weight ( P<0.001 ) , nutritional status ( P=0.020 ) and global QoL ( P=0.009 ) compared with those receiving UC . Clinical ly , but not statistically significant differences in fat-free mass were observed between the groups ( P=0.195 ) . Early and intensive NI appears beneficial in terms of minimising weight loss , deterioration in nutritional status , global QoL and physical function in oncology out patients receiving radiotherapy to the GI or head and neck area . Weight maintenance in this population leads to beneficial outcomes and suggests that this , rather than weight gain , may be a more appropriate aim of NI Background Dysphagia occurs in up to 50 % of patients admitted to hospital with acute strokes with up to 27 % remaining by seven days . Up to 8 % continue to have swallowing problems six months after their stroke with 1.7 % still requiring enteral feeding . Nasogastric tubes ( NGT ) are the most commonly used method for providing enteral nutrition in early stroke , however they are easily and frequently removed leading to inadequate nutrition , early PEG ( Percutaneous Endoscopic Gastrostomy ) insertion or ab and oning of feeding attempts . Looped nasogastric tube feeding may improve the delivery of nutrition to such patients . Methods Three centre , two arm r and omised controlled trial , with 50 participants in each arm comparing loop ( the intervention ) versus conventional nasogastric tube feeding . The primary outcome measure is proportion of intended feed delivered in the first 2 weeks . The study is design ed to show a mean increase of feed delivery of 16 % in the intervention group as compared with the control group , with 90 % power at a 5 % significance level . Secondary outcomes are treatment failures , mean volume of feed received , adverse events , cost-effectiveness , number of chest x-rays , number of nasogastric tubes and tolerability . Trial Registration IS RCT N Number : IS RCT This is a prospect i ve case-control study to assess nutritional supplementation in limiting weight loss and its impact on daily set-up variations and planning target volume ( PTV ) margins in head and neck ( H&N ) radiotherapy ( RT ) . Twenty sequential H&N patients were recruited for this study . Ten patients had a percutaneous endoscopic gastrostomy ( PEG ) tube inserted prior to RT and 10 did not . PEG use was determined by departmental guidelines for patients considered at high risk for weight loss . Daily 2D electronic portal images were taken for orthogonal verification . Set-up variations were determined for both PEG and non-PEG patients by calculating systematic ( Sigma ) and r and om ( sigma ) errors , and PTV margins were derived . PEG patients lost less weight ( P = 0.04 ) over the course of RT and had a reduction in set-up variation in the superior-inferior ( SI ) and anterior-posterior ( AP ) planes compared to those without . Mean correctional shifts in mm ( range ) for PEG patients were : Right-Left ( RL ) 0.1 ( -1.9 - 2.1 ) , SI -1.7 ( -2.9 - 0.0 ) , AP -0.4 ( -2.0 - 0.8 ) , and for non-PEG patients were : RL -0.2 ( -2.7 - 1.3 ) , SI -1.3 ( -3.1 - 1.0 ) , AP 0.4 ( -1.5 - 2.8 ) . The adapted PTV margins ( mm ) in the RL , SI and AP planes , respectively , for PEG patients were 4.1 , 3.3 and 3.6 , and for non-PEG were 3.9 , 4.9 and 4.8 . Intensive enteral support maintained weight stability in H&N patients considered at risk of weight loss during RT and this was associated with reduced set-up variation OBJECTIVES /HYPOTHESIS Percutaneous endoscopic gastrostomy tube ( PEG ) placement by means of the " pull " method has been reported to result in a significantly higher complication rate when compared with " push " PEG placement . These findings have led to a renewed interest in the push , or Russell introducer , method of PEG placement at the authors ' institution when PEG is required before definitive treatment of advanced head and neck cancer . The authors sought to determine whether the push method of PEG placement is associated with a lower incidence of complications in this patient population . STUDY DESIGN Nonr and omized , retrospective patient analysis . METHODS The medical records of all patients presenting to the Medical College of Georgia ( Augusta , GA ) who received a diagnosis of squamous cell carcinoma of the head and neck between 1999 to 2001 were retrospectively review ed . Patients who required PEG placement as part of their treatment comprised the study population . RESULTS The push PEG technique was used in 29 patients , and the pull technique was used in 50 patients . There was a statistically significant difference in the complication rate between the two techniques . Patients who underwent placement by means of the pull technique had an overall complication rate of 30 % ( 15 of 50 ) versus a 0 % ( 0 of 29 ) complication rate in patients undergoing the push technique ( P = .0006 , Fisher 's Exact test ) . CONCLUSION The push PEG technique appears to have a significantly lower risk of complications compared with the pull technique in patients with advanced head and neck cancer . The authors recommend considering the use of the push method when PEG placement is required ABSTRACT To compare the efficacy of percutaneous endoscopic gastrostomy ( PEG ) and nasogastric ( NGT ) tube administration of enteral nutrition in head and neck cancer patients undergoing curative treatment , the authors conducted a prospect i ve study to compare nutritional outcomes , complications , and patient satisfaction . PEG patients sustained significantly less reduction in nutritional parameters , measured at 6 weeks post insertion , as compared with NGT patients . There was also a statistically significant difference between the two groups in patient 's quality of life scores and complications . Comparison could not be done at 6 months because all patients were converted to PEG feeding due to the earlier findings . The authors conclude that PEG is more efficacious than NGT as a channel for nutrition in advanced head and neck cancer patients over a short duration The aim of this prospect i ve two year study was to compare the outcome of two methods of nutritional support , namely nasogastric [ NG ] and percutaneous endoscopic gastrostomy [ PEG ] feeding implemented for head and neck cancer patients unable to maintain their nutritional status whilst receiving radiotherapy treatment at a regional oncology unit . The nutritional requirements of the 100 patients included in the study were calculated and an enteral feeding regime implemented to ensure the nutritional requirements of each individual patient were met . Any changes in the weight and body mass index [ BMI ] of each patient during the study period were documented . The method of delivery , composition of feed and duration of nutritional support of each feeding method were determined . The feeding methods were found to be equally effective at maintaining body weight . Patients with NG tubes in situ were more frequently prescribed a st and ard 1 kcal/ml feed administered via an enteral feeding pump , whereas patients with PEG tubes in situ were more frequently prescribed a high energy 1.5 Kcal/ ml feed administered by the bolus method . A number of advantages are associated with PEG feeding including greater mobility , cosmesis and quality of life . Evidence indicates the outcome of radiotherapy treatment is not as favourable if interrupted , therefore , it is essential PEG tubes are sited prior to commencing treatment , illustrating the necessity for dietetic intervention for every patient to be addressed and incorporated into the treatment plan on diagnosis of head and neck cancer before definitive management commences BACKGROUND Percutaneous endoscopic gastrostomy ( PEG ) tubes have largely replaced nasogastric tubes ( NGTs ) for nutritional support of patients with head and neck cancer undergoing curative ( chemo ) radiotherapy without any good scientific basis . METHODS A prospect i ve study was conducted to compare PEG tubes and NGTs in terms of nutritional outcomes , complications , patient satisfaction , and cost . RESULTS There were 32 PEG and 73 NGT patients . PEG patients sustained significantly less weight loss at 6 weeks post-treatment ( median 0.8 kg gain vs 3.7 kg loss , p < .001 ) , but had a high insertion site infection rate ( 41 % ) , longer median duration of use ( 146 vs 57 days , p < .001 ) , and more grade 3 dysphagia in disease-free survivors at 6 months ( 25 % vs 8 % , p = .07 ) . Patient self-assessed general physical condition and overall quality of life scores were similar in both groups . Overall costs were significantly higher for PEG patients . CONCLUSION PEG tube use should be selective , not routine , in this patient population BACKGROUND AND STUDY AIMS Infection of the gastrostomy opening after placement of a percutaneous endoscopic gastrostomy ( PEG ) catheter has been reported to occur quite often , especially when the pull method is used . We therefore compared complications occurring with the pull and push methods , and evaluated the role of antibiotic prophylaxis . PATIENTS AND METHODS In a prospect i ve study , 100 consecutive patients Output:	It became apparent from our studies that both feeding strategies have advantages and disadvantages
MS2787	*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: Reports of cluster r and omised trials require additional information to allow readers to interpret them accurately The effective reporting of r and omised controlled trials has received useful attention in recent years . Many journals now require that reports conform to the guidelines in the Consoli date d St and ards of Reporting Trials ( CONSORT ) statement , first published in 1996 and revised in 2001 . The statement includes a checklist of items that should be included in the trial report . These items are evidence based whenever possible and are regularly review ed . The statement also recommends including a flow diagram to show the flow of participants from group assignment through to the final analysis . The CONSORT statement focused on reporting parallel group r and omised trials in which individual participants are r and omly assigned to study groups . However , in some situations it is preferable to r and omly assign groups of individuals ( such as families or medical practice s ) rather than individuals . Reasons include the threat of contamination of some interventions ( such as dietary interventions ) if individual r and omisation is used . 5 Also , in certain setting s r and omisation by group may be the only feasible method of conducting a trial . Trials with this design are variously known as field trials , community based trials , place based trials , or ( as in this paper ) cluster r and omised trials . In an earlier discussion paper we considered the implication s of the CONSORT statement for the reporting of cluster r and omised trials . Here we present up date d guidance , based on the 2001 revision of the CONSORT statement This study reports the evaluation of an intervention design edto reinforcetobacco abstinence amongelementary schoolchildren in a school transition period . This intervention was developed according to the principles of Intervention Mapping . A total of 765 grade 5 students ( ages 10 - 12 ) was recruited in 32 elementary schools . A quasi-experimental longitudinal design was used to evaluate the outcomes . Results observed 2 and 8 months postintervention are reported here . It is shown that although the behavior remained largely unchanged by the intervention , some of its determinants were modified . Behavioral intention , behavioral and normative beliefs , perceived self-efficacy , and role beliefs were changed at one or both postintervention measures . An interesting feature of these results relates to the fact that the most positive outcomes were seen among at-risk children . Discussion considers the advisability to develop , implement , and evaluate evidence -based interventions targeting the psychosocial factors underlying maintenance of tobacco smoking abstinence in elementary school Most school-based smoking prevention studies employ design s in which schools or classrooms are assigned to different treatment conditions while observations are made on individual students . This design requires that the treatment effect be assessed against the between-school variance . However , the between-school variance is usually larger than the variance that would be obtained if students were individually r and omized to different conditions . Consequently , the power of the test for a treatment effect is reduced , and it becomes difficult to detect important treatment effects . To assess the potential loss of power or to calculate appropriate sample sizes , investigators need good estimates of the intraclass correlations for the variables of interest . The authors calculated intraclass correlations for some common outcome variables in a school-based smoking prevention study , using a three-level model-i.e . , students nested within classrooms and classrooms nested within schools . The authors present the intraclass correlation estimates for the entire data set , as well as separately by sex and ethnicity . They also illustrate the use of these estimates in the planning of future studies Bruno Giraudeau and Philippe Ravaud discuss the difficulties in preventing selection bias and applying intention-to-treat analysis in cluster r and omized trials , and propose some solutions BACKGROUND The 1985 Minnesota Legislature established guidelines for school-based tobacco-use prevention programming and provided financial incentives to school districts to encourage them to adopt a broad range of preventive measures . The Minnesota-Wisconsin Adolescent Tobacco-Use Research Project was funded by the National Cancer Institute in 1986 to evaluate the Minnesota initiative through two parallel studies . METHODS The Four Group Comparison Study was a prospect i ve study of 48 school " units " which were r and omly assigned to one of four conditions in 1987 . Baseline observations were taken in the sixth grade in 1987 , interventions were delivered in the seventh grade , and follow-up observations were taken in the seventh , eighth , and ninth grade s. The Four Group Comparison Study was design ed to evaluate the three middle-school interventions that were most widely adopted by Minnesota school districts as a result of the 1985 legislation . The Two State Comparison Study was a serial cross-sectional study of representative districts in Minnesota and Wisconsin . Annual surveys of ninth grade rs were conducted from 1986 - 1990 . The Two State Comparison Study was design ed to determine whether tobacco-use patterns changed in Minnesota relative to Wisconsin following the Minnesota legislation . RESULTS The prospect i ve study indicated that none of the interventions was more effective in reducing adolescent tobacco use compared with a r and omized control group . The serial cross-sectional study revealed that there was a modest net decline in Minnesota relative to Wisconsin from 1986 to 1990 , but that it was within the range of chance variation . CONCLUSIONS Taken together , these results indicate that this legislative initiative was insufficient to reduce adolescent tobacco use statewide during the 5-year study period . Together with results from other recent studies , they suggest that even more intensive efforts may be required to effect widespread reductions in adolescent tobacco use BACKGROUND Smoking is the leading preventable cause of premature death in the United States . Previous studies of financial incentives for smoking cessation in work setting s have not shown that such incentives have significant effects on cessation rates , but these studies have had limited power , and the incentives used may have been insufficient . METHODS We r and omly assigned 878 employees of a multinational company based in the United States to receive information about smoking-cessation programs ( 442 employees ) or to receive information about programs plus financial incentives ( 436 employees ) . The financial incentives were $ 100 for completion of a smoking-cessation program , $ 250 for cessation of smoking within 6 months after study enrollment , as confirmed by a biochemical test , and $ 400 for abstinence for an additional 6 months after the initial cessation , as confirmed by a biochemical test . Individual participants were stratified according to work site , heavy or nonheavy smoking , and income . The primary end point was smoking cessation 9 or 12 months after enrollment , depending on whether initial cessation was reported at 3 or 6 months . Secondary end points were smoking cessation within the first 6 months after enrollment and rates of participation in and completion of smoking-cessation programs . RESULTS The incentive group had significantly higher rates of smoking cessation than did the information-only group 9 or 12 months after enrollment ( 14.7 % vs. 5.0 % , P<0.001 ) and 15 or 18 months after enrollment ( 9.4 % vs. 3.6 % , P<0.001 ) . Incentive-group participants also had significantly higher rates of enrollment in a smoking-cessation program ( 15.4 % vs. 5.4 % , P<0.001 ) , completion of a smoking-cessation program ( 10.8 % vs. 2.5 % , P<0.001 ) , and smoking cessation within the first 6 months after enrollment ( 20.9 % vs. 11.8 % , P<0.001 ) . CONCLUSIONS In this study of employees of one large company , financial incentives for smoking cessation significantly increased the rates of smoking cessation . ( Clinical Trials.gov number , NCT00128375 . Objective : To assess the effect of an antismoking intervention focusing on adolescents in lower education . Students with lower education smoke more often and perceive more positive norms , and social pressure to smoke , than higher educated students . An intervention based on peer group pressure and social influence may therefore be useful to prevent smoking among these students . Design : Group r and omised controlled trial . Setting : 26 Dutch schools that provided junior secondary education . Subjects : 1444 students in the intervention and 1118 students in the control group , all in the first grade , average age 13 years . Intervention : Three lessons on knowledge , attitudes , and social influence , followed by a class agreement not to start or to stop smoking for five months and a class based competition . Main outcome measures : Comparison of smoking status before and immediately after and one year after the intervention , using multilevel analysis . Results : In the intervention group , 9.6 % of non-smokers started to smoke , in the control group 14.2 % . This leads to an odds ratio of 0.61 ( 95 % CI= 0.41 to 0.90 ) to uptake smoking in the intervention group compared with the control group . One year after the intervention , the effect was no longer significant . Conclusions : In the short-term , an intervention based on peer pressure decreases the proportion of adolescents with lower education who start smoking . Influencing social norms and peer pressure would therefore be a promising strategy in terms of preventing smoking among adolescents . The results also suggest that additional interventions in later years are needed to maintain the effect OBJECTIVES This study examined the effect of an orthodontist-delivered tobacco-use prevention program for adolescents . METHODS Southern California orthodontic offices were r and omly assigned to experimental ( n = 77 ) and control ( n = 77 ) groups . R and omly selected adolescents were interviewed at baseline and 2 years later ( n = 15,644 ) . Experimental offices received tobacco prevention training , anti-tobacco material s , and 50 cents for each anti-tobacco " prescription " written . RESULTS The 30-day tobacco use 2-year incidence rates for the control and experimental groups were 12.6 % and 12.0 % , respectively ; incidence rates for using tobacco more than 100 times were 7.6 % and 6.8 % . Differences between the groups did not reach significance . Mean prescription compliance was 64.4 % . A multivariate logistic model , showed a significant dose response : patients who received more prescriptions had lower incidence rates than those who received few or none ( 10 % vs 14 % ) . CONCLUSIONS Training , payment , and support did not ensure clinician compliance with prevention services . The dose effect suggests that replication under conditions that would ensure clinician compliance and statistical power would more thoroughly test clinicians ' ability to prevent tobacco use OBJECTIVES We assessed the effectiveness of a 2-year multicomponent , school-based intervention design ed to reduce tobacco use rates among adolescents in an urban area of India . METHODS Students from 32 schools in Delhi and Chennai , India , were recruited and r and omly assigned to an intervention or control group . Baseline , intermediate , and outcome data were collected from 2 cohorts of 6th- and 8th- grade students in 2004 ; 14,063 students took part in the study and completed a survey in 2004 , 2005 , or 2006 . The intervention consisted of behavioral classroom curricula , school posters , a parental involvement component , and peer-led activism . The main outcome measures were self-reported use of cigarettes , bidis ( small h and -rolled , often flavored , cigarettes ) , and chewing tobacco and future intentions to smoke or use chewing tobacco . RESULTS Findings showed that students in the intervention group were significantly less likely than were students in the control group to exhibit increases in cigarette smoking or bidi smoking over the 2-year study period . They were also less likely to intend to smoke or chew tobacco in the future . CONCLUSIONS School-based programs similar to the intervention examined here should be considered as part of a multi strategy approach to reducing tobacco use among young people in India BACKGROUND This paper examines the effectiveness of the " Smokefree Class Competition " with regard to primary and secondary prevention of smoking in adolescents . Each participating class has to decide if they want to be a " Smokefree Class " for the six-month period from fall to spring . Classes monitor their (non-)smoking behaviour and report it to the teacher regularly . Classes in which pupils refrain from smoking for this period of time participate in a prize draw , where they can win a number of attractive prizes . METHODS A control group study with repeated measurements was carried out in order to evaluate the effectiveness of the competition . The sample consisted of 131 participating and non-participating classes ( N of the pupils = 2,142 ; mean age 12.9 years , SD = 0.98 ) . Smoking status was assessed on two occasions : ( a ) prior to the beginning of the competition , and ( b ) 6 month after the end of the competition . RESULTS With regard to the smoking status at baseline no differences could be found between the experimental and the control group ( 15.2 % vs. 18.5 % smoking pupils ) . In the follow-up measurement , pupils in the control group showed significantly higher prevalences of smoking than the experimental group in the post-measurement period ( 32.9 % vs. 25.5 % smoking pupils ) . More pupils in the experimental group stayed smokefree compared to the control group . No differential effects on smoking cessation could be found . CONCLUSIONS The results show that participation in the competition could delay the onset of smoking in adolescents ( primary prevention ) . The competition is not effective in smoking cessation in youth OBJECTIVES Previous research has suggested that early smoking initiation predicts longer duration of smoking , heavier daily consumption , and increased chances of nicotine dependence . This report set out to estimate the relationship between smoking cessation and age of initiation , as well as nicotine dependence , sex , race , and education . METHODS A sample of 1007 young adults was r and omly Output:	There is little robust evidence to suggest that unintended consequences ( such as youth making false cl aims about their smoking status and bullying of smoking students ) are consistently associated with such interventions , although this has not been the focus of much research .
MS2788	*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 — Among patients with acute stroke , high blood pressure is often associated with poor outcome , although the reason is unclear . We analyzed data from the International Stroke Trial ( IST ) to explore the relationship between systolic blood pressure ( SBP ) , subsequent clinical events over the next 2 weeks , and functional outcome at 6 months in patients with acute stroke . Methods — We included in the analysis 17 398 patients from IST with confirmed ischemic stroke . A single measurement of SBP was made immediately before r and omization . Clinical events within 14 days of r and omization were recorded : recurrent ischemic stroke , symptomatic intracranial hemorrhage , death result ing from presumed cerebral edema , fatal coronary heart disease , and death . Survival and dependency were assessed at 6 months . Outcomes were adjusted for age , sex , clinical stroke syndrome , time to r and omization , consciousness level , atrial fibrillation , and treatment allocation ( aspirin , unfractionated heparin , both , or neither ) . Results — A U-shaped relationship was found between baseline SBP and both early death and late death or dependency : early death increased by 17.9 % for every 10 mm Hg below 150 mm Hg ( P < 0.0001 ) and by 3.8 % for every 10 mm Hg above 150 mm Hg ( P = 0.016 ) . The rate of recurrent ischemic stroke within 14 days increased by 4.2 % for every 10–mm Hg increase in SBP ( P = 0.023 ) ; this association was present in both fatal and nonfatal recurrence . Death result ing from presumed cerebral edema was independently associated with high SBP ( P = 0.004 ) . No relationship between symptomatic intracranial hemorrhage and SBP was seen . Low SBP was associated with a severe clinical stroke ( total anterior circulation syndrome ) and an excess of deaths from coronary heart disease ( P = 0.002 ) . Conclusions — Both high blood pressure and low blood pressure were independent prognostic factors for poor outcome , relationships that appear to be mediated in part by increased rates of early recurrence and death result ing from presumed cerebral edema in patients with high blood pressure and increased coronary heart disease events in those with low blood pressure . The occurrence of symptomatic intracranial hemorrhage within 14 days was independent of SBP Background and Purpose — The practicalities of doing ambulance-based trials where paramedics perform all aspects of a clinical trial involving patients with ultra-acute stroke have not been assessed . Methods — We performed a r and omized controlled trial with screening , consent , r and omization , and treatment performed by paramedics prior to hospitalization . Patients with probable ultra-acute stroke ( < 4 hours ) and systolic blood pressure ( SBP ) > 140 mm Hg were r and omized to transdermal glyceryl trinitrate ( GTN ; 5 mg/24 hours ) or none ( blinding under gauze dressing ) for 7 days with the first dose given by paramedics . The primary outcome was SBP at 2 hours . Results — Of a planned 80 patients , 41 ( 25 GTN , 16 no GTN ) were enrolled > 22 months with median age [ interquartile range ] 79 [ 16 ] years ; men 22 ( 54 % ) ; SBP 168 [ 46 ] ; final diagnosis : stroke 33 ( 80 % ) and transient ischemic attack 3 ( 7 % ) . Time to r and omization was 55 [ 75 ] minutes . After treatment with GTN versus no GTN , SBP at 2 hours was 153 [ 31 ] versus 174 [ 27 ] mm Hg , respectively , with difference −18 [ 30 ] mm Hg ( P=0.030 ) . GTN improved functional outcome with a shift in the modified Rankin Scale by 1 [ 3 ] point ( P=0.040 ) . The rates of death , 4 ( 16 % ) versus 6 ( 38 % ; P=0.15 ) , and serious adverse events , 14 ( 56 % ) versus 10 ( 63 % ; P=0.75 ) , did not differ between GTN and no GTN . Conclusions — Paramedics can successfully enroll patients with ultra-acute stroke into an ambulance-based trial . GTN reduces SBP at 2 hours and seems to be safe in ultra-acute stroke . A larger trial is needed to assess whether GTN improves functional outcome . Clinical Trial Registration — URL : http://www.controlled-trials.com/IS RCT N66434824/66434824 . Unique identifier : 66434824 High blood pressure ( BP ) , pulse pressure ( PP ) , and rate pressure product ( RPP ) are each associated independently with a poor outcome in acute ischemic stroke . Whereas nitric oxide ( NO ) donors , such as glyceryl trinitrate ( GTN ) , lower blood pressure in acute ischemic stroke , their effect on other hemodynamic measures is not known . We performed a systematic review of the effects of NO donors on systemic hemodynamic measures in patients with acute/subacute stroke . R and omized controlled trials were identified from search es of the Cochrane Library , Pubmed , and Embase . Information on hemodynamic measures , including systolic BP ( SBP ) , diastolic BP ( DBP ) , and heart rate , were assessed , and hemodynamic derivatives of these were calculated : PP ( PP = SBP - DBP ) , mean arterial pressure ( MAP = DBP + PP/3 ) , mid blood pressure ( MBP = ( SBP + DBP)/2 ) , pulse pressure index ( PPI = PP/MAP ) , and RPP ( RPP = SBP x HR ) . The effect of treatment on hemodynamic measures was calculated as the weighted mean difference ( WMD ) between treated and control groups with adjustment for baseline . Three trials involving 145 patients were identified ; 93 patients received the NO donor , GTN , and 52 patients composed the control group . Compared with placebo , GTN significantly reduced SBP ( WMD , -9.80 mm Hg ; P < .001 ) , DBP ( WMD , -4.43 mm Hg ; P < .001 ) , MAP ( WMD , - 6.41 mm Hg ; P < .001 ) , MBP ( WMD , -7.33 mm Hg ; P < .001 ) , PP ( WMD , -6.11 mm Hg ; P < .001 ) , and PPI ( WMD , -0.03 ; P = .04 ) . GTN increased HR ( WMD , + 3.87 bpm ; P < .001 ) and lowered RPP insignificantly ( WMD , -323 mm Hg.bpm ; P = .14 ) . Our findings indicate that the NO donor GTN reduces BP , PP , and other derivatives in acute and subacute stroke while increasing HR High blood pressure is common during the acute phase of stroke and is associated with a poor outcome . However , the management of high blood pressure remains unclear . The ‘ Efficacy of Nitric Oxide in Stroke ’ trial tested whether transdermal glyceryl trinitrate , a nitric oxide donor that lowers blood pressure , is safe and effective in improving outcome after acute stroke . Efficacy of Nitric Oxide in Stroke is an international multicenter , prospect i ve , r and omized , single-blind , blinded endpoint trial , with funding from the UK Medical Research Council . Patients with acute ischemic stroke or intracerebral hemorrhage and systolic blood pressure 140–220 mmHg were r and omized to glyceryl trinitrate or no glyceryl trinitrate and , where relevant , to continue or stop prestroke antihypertensive therapy . The primary outcome is shift in modified Rankin Scale at three-months . Patients or relatives gave written informed ( proxy ) consent , and all sites had research ethics approval . Analyses will be done by intention to treat . This paper and attachment describe the trial 's statistical analysis plan , developed prior to unblinding of date . The statistical analysis plan contains design and methods for analyses , and unpopulated tables and figures for the two primary publications and some secondary publications . The data base will be locked in late February 2014 in preparation for presentation of the results in May 2014 . The data from the trial will improve the precision of the estimates of the overall treatment effects ( efficacy and safety ) of results from completed trials of blood pressure management in acute stroke , and provide the first large-scale r and omized evidence on transdermal glyceryl trinitrate , and of continuing ( vs. stopping ) prestroke antihypertensive medications , in acute stroke High blood pressure in acute stroke is common and appears to be associated with a poor outcome . Lowering blood pressure might therefore improve outcome , provided that cerebral perfusion is not compromised . We assessed the effects of glyceryl trinitrate ( GTN ) on cerebral and systemic hemodynamic measures in acute stroke . Ninety patients with acute ischemic or hemorrhagic stroke were r and omized within 72 hours of ictus to transdermal GTN given daily for 10 days ( either 5 mg , 5 mg for 4 days then 10 mg , or 10 mg ) or control . Twenty-four hour blood pressure monitoring , middle cerebral artery blood velocity , cardiac output , augmentation index , and plasma nitric oxide levels were each measured at baseline and then on days 1 , 4 , 5 , and 10 . The primary outcome was blood pressure on day 1 . We found that GTN lowered mean peripheral arterial blood pressure on day 1 by 5.3 % to 6.7 % in a dose dependent manner as compared with control ( mean , SD ) : control , 108.8 ( 15.1 ) mmHg ; 5 mg , 102.5 ( 13.9 ) mmHg ; 5/10 mg , 103.4 ( 14.9 ) mmHg ; 10 mg , 101.5 ( 12.6 ) mmHg ; ( P = .005 ) . Increasing the dose from 5 to 10 mg on day 5 result ed in an overall reduction in blood pressure of 11.4 % as compared with leaving the dose at 5 mg ( P = .006 ) . GTN reduced peripheral pulse pressure , central aortic blood pressure , pulse pressure , and augmentation index on day 1 . Middle cerebral artery blood velocity and pulsatility index in the affected hemisphere , cardiac output , systemic peripheral resistance , and plasma nitric oxide levels were not altered by GTN . Treatment with GTN was associated with headache : control 0 ( 0 % ) , GTN 9 ( 15 % ) ( P = .027 ) ; no negative effect on end-of-treatment death or deterioration , or 3 month death or dependency was discernable . GTN reduced peripheral blood pressure in a dose-dependent fashion in patients with acute stroke at day 1 and also reduced central blood pressure and augmentation index . In contrast , GTN did not alter middle cerebral artery blood velocity or pulsatility index in the affected hemispheres , suggesting that cerebral blood flow did not change . A trial assessing the effect of lowering blood pressure with GTN on safety and functional outcome in patients with acute stroke is now warranted Background : Cellular phone conversations between on-scene patients or their legally authorized representatives ( LARs ) and off-scene enrolling physician-investigators require immediate and reliable connection systems to obtain explicit informed research consent in prehospital treatment trials . Methods : The NIH Field Administration of Stroke Therapy – Magnesium ( FAST-MAG ) Trial implemented a voice-over-internet protocol ( VOIP ) simultaneous ring system ( multiple investigator cell phones called simultaneously and first responder connected to call ) to enable physician-investigators to elicit consent immediately from competent patients or LARs encountered by 228 ambulances enrolling patients in a multicenter prehospital stroke trial . For 1 month , the number , origin , duration , and yield of enrolling line calls were monitored prospect ively . Results : Six investigators were connected to 106 enrolling line calls , with no identified unanswered calls . Thirty-five percent of new patient calls yielded an enrollment . The most common reasons for non-enrollment were last known well > 2 h ( n = 7 ) and uncon sentable patient without LAR available ( n = 7 ) . No non-enrollments were directly attributable to the VOIP system . In enrollments , consent was provided by the patient in 67 % and a LAR in 33 % . The duration of enrollment calls ( mean ± SD : 8.4 ± 2.5 min , range 6–14 ) was longer than non-enrollment calls ( 5.5 ± 3.5 , range 2–13 ; p < 0.001 ) . The median interval from last known well to study agent start was 46 min , and 70 % were enrolled within 60 min of onset . Conclusions : The simultaneous ring system was reliable and effective , permitting enrollment of a substantial number of patients within the first hour after stroke onset . VOIP cellular networks with simultaneous ring are a preferred means of facilitating consent in prehospital treatment trials High blood pressure ( BP ) is common in acute stroke and is independently associated with a poor outcome . Lowering BP might improve outcome if it did not adversely affect cerebral blood flow ( CBF ) or cerebral perfusion pressure . We investigated the effect of glyceryl trinitrate ( [ GTN ] an NO donor ) on quantitative CBF , BP , and cerebral perfusion pressure in patients with recent stroke . Eighteen patients with recent ( < 5 days ) ischemic ( n=16 ) Output:	ENOS is a large completed international trial of blood pressure management in acute stroke and includes patients representative of many stroke services worldwide
MS2789	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Abstract Objective : To evaluate the effectiveness of combinations of three methods to promote physical activity . Design : R and omised controlled trial . Baseline assessment with post-intervention follow up at 12 weeks and 1 year . Setting : One urban general practice , 1995 - 7 . Participants : 523 adults aged 40 to 64 years , r and omised to four intervention groups and a control group . Interventions : Brief ( one interview ) or intensive ( six interviews over 12 weeks ) motivational interviewing based on the stages of change model of behaviour change , with or without financial incentive ( 30 vouchers entitling free access to leisure facilities ) . Main outcome measures : Physical activity score ; sessions of moderate and vigorous activity in the preceding four weeks . Results : Response rate was 81 % at 12 weeks and 85 % at one year . More participants in the intervention group reported increased physical activity scores at 12 weeks than controls ( 38 % v 16 % , difference 22 % , 95 % confidence interval for difference 13 % to 32 % ) , with a 55 % increase observed in those offered six interviews plus vouchers . Vigorous activity increased in 29 % of intervention participants and 11 % of controls ( difference 18 % , 10 % to 26 % ) , but differences between the intervention groups were not significant . Short term increases in activity were not sustained , regardless of intensity of intervention . Conclusions : The most effective intervention for promoting adoption of exercise was the most intensive . Even this did not promote long term adherence to exercise . Brief interventions promoting physical activity that are used by many schemes in the United Kingdom are of question able effectiveness . Key messages Schemes promoting physical activity are currently popular in general practice in Britain , but few have been rigorously evaluated and their effectiveness is unknown . In this study , the most effective intervention for promoting adoption of physical activity was the most intensive , involving six motivational interviews and a financial incentive A comparatively brief intervention ( one interview ) was only effective in the short term in around a third of participants Short term increases in physical activity were not maintained at one year follow up and even the most intensive intervention was ineffective in promoting long term adherence to increased physical activity . National and local government , health authorities , and primary healthcare teams should be cautious about current and future expenditure on , and implementation of , exercise prescription or referral Background and Purpose — A new gait training strategy for patients with stroke seeks to increase walking speed through treadmill training . This study compares the effects of structured speed-dependent treadmill training ( STT ) ( with the use of an interval paradigm to increase the treadmill speed stepwise according to principles of sport physiology ) with limited progressive treadmill training ( LTT ) and conventional gait training ( CGT ) on clinical outcome measures for patients with hemiparesis . Methods — Sixty ambulatory poststroke patients were each r and omly selected to receive 1 of the 3 different gait therapies : 20 subjects were treated with STT , 20 subjects were trained to walk on a treadmill with a 20 % increase of belt speed over the treatment period ( LTT ) , and 20 subjects were treated with CGT . Treatment outcomes were assessed on the basis of overground walking speed , cadence , stride length , and Functional Ambulation Category scores . Results — After a 4-week training period , the STT group scored significantly higher than the LTT and CGT groups for overground walking speed ( STT versus LTT , P < 0.001 ; STT versus CGT , P < 0.001 ) , cadence ( STT versus LTT , P = 0.007 ; STT versus CGT , P < 0.001 ) , stride length ( STT versus LTT , P < 0.001 ; STT versus CGT , P < 0.001 ) , and Functional Ambulation Category scores ( STT versus LTT , P = 0.007 ; STT versus CGT , P < 0.001 ) . Conclusions — Structured STT in poststroke patients result ed in better walking abilities than LTT or CGT . This gait training strategy provides a dynamic and integrative approach for the treatment of gait dysfunction after stroke Abstract The evaluation of a 13-month maintenance program ( MP ) for 39 severe COPD patients with FEV1%pred 44(7)% who , as result of two different 8-week leg exercise training ( LET ) programs , one supervised at the hospital ( group S ; n = 20 ) and the other self-monitored ( SM ; n = 19 ) , had achieved different levels of exercise tolerance . After LET , patients in group S had a higher maximal oxygen uptake and endurance time than patients in the SM group [ O2max 1.43(0.30 ) l · min−1 ] vs l.25(0.27 ) l · min−1 and endurance-time 16(4 ) min vs 12 ( 5 ) min , respectively ) . During the MP patients were advised to walk vigorously at least 4 km/day , 4 times/wk . After the MP , while endurance time remained higher than at baseline , it had decreased ( p < 0.01 ) immediately after LET in both groups and no differences were evident between groups ( 11(4 ) min and 10(4 ) , respectively ) . In contrast , Chronic Respiratory Diseases Question naire scores , which had improved significantly after LET in both groups , remained high . Long-term effects of MP were independent of the training strategy or whether physiological improvements had been obtained with the initial LET . SM exercise programs do not seem capable of maintaining physiological improvements in exercise tolerance , though “ quality of life ” can be maintained The purpose of this study was to determine the effect of intensity-controlled , grade d dance exercise and selected components of behavior modification on exercise adherence in overweight middle-aged women . Thirty-eight moderately overweight women , aged 35 to 58 , participated in a 16 1/2-week dance exercise program . Participants were r and omly assigned to an experimental group ( n = 20 ) that received intensity-controlled , grade d exercise and individual and group reinforcement , or to a control group ( n - 18 ) that exercised at a moderate intensity typical of commercial fitness classes and received no special reinforcement . Before exercise training began and at the completion of 16 1/2 weeks , a structured , open-ended interview was conducted . Ninety-four percent of the women in both groups adhered to the program , an exceptionally high adherence rate for this population . Eight participantidentified factors seemed to have influenced exercise adherence : group homogeneity , carpooling and social networks , pleasurable feelings associated with increased energy and fitness , leader with a health-related background , time limitation of exercise program , commitment to an established goal , desire to change body image , and desire to change health status and improve physical health BACKGROUND In patients with intermittent claudication , a supervised walking exercise program increases peak exercise performance and community-based functional status . Patients with peripheral arterial disease also have muscle weakness in the affected extremity that may contribute to the walking impairment . However , the potential benefits of training modalities other than walking exercise , such as strength training , have not been critically evaluated in this patient population . The present study tested the hypothesis that a strength training program would be as effective as treadmill walking exercise and that combinations of strengthening and walking exercise would be more effective than either alone in improving exercise performance . METHODS AND RESULTS Twenty-nine patients with disabling claudication were r and omized to 12 weeks of supervised walking exercise on a treadmill ( 3 h/wk at a work intensity sufficient to produce claudication ) , strength training ( 3 h/wk of resistive training of five muscle groups of each leg ) , or a nonexercising control group . Grade d treadmill testing was performed to maximally tolerated claudication pain to define changes in peak exercise performance . After 12 weeks , patients in the treadmill training program had a 74 + /- 58 % increase in peak walking time as well as improvements in peak oxygen consumption ( VO2 ) and the onset of claudication pain . Patients in the strength-trained group had a 36 + /- 48 % increase in peak walking time but no change in peak VO2 or claudication onset time . Control subjects had no changes in any of these measures over the 12-week period . After the first 12 weeks , patients in the initial walking exercise group continued for 12 more weeks of supervised treadmill training . This result ed in an additional 49 + /- 53 % increase in peak walking time ( total of 128 + /- 99 % increase over the 24 weeks ) . After the initial 12 weeks , patients in the strength-trained group began 12 weeks of supervised treadmill training , and patients in the control group participated in a 12-week combined program of strengthening and treadmill walking exercise . The combined strength and treadmill training program and treadmill training after 12 weeks of strength training result ed in increases in peak exercise performance similar to those observed with 12 weeks of treadmill training alone . CONCLUSIONS A supervised treadmill walking exercise program is an effective means to improve exercise performance in patients with intermittent claudication , with continued improvement over 24 weeks of training . In contrast , 12 weeks of strength training was less effective than 12 weeks of supervised treadmill walking exercise . Finally , strength training , whether sequential or concomitant , did not augment the response to a walking exercise program BACKGROUND Project ACTIVE was a r and omized clinical trial comparing two physical activity interventions , lifestyle and traditional structured exercise . The two interventions were evaluated and compared in terms of cost effectiveness and ability to enhance physical activity among sedentary adults . DESIGN This was a r and omized clinical trial . SETTING / PARTICIPANTS The study included 235 sedentary but healthy community-dwelling adults . INTERVENTION A center-based lifestyle intervention that consisted of behavioral skills training was compared to a structured exercise intervention that included supervised , center-based exercise . MAIN OUTCOME MEASURES The main outcome measures of interest included cost , cardiorespiratory fitness , and physical activity . RESULTS Both interventions were effective in increasing physical activity and fitness . At 6 months , the costs of the lifestyle and structured interventions were , respectively , $ 46.53 and $ 190.24 per participant per month . At 24 months these costs were $ 17.15 and $ 49.31 per participant per month . At both 6 months and 24 months , the lifestyle intervention was more cost-effective than the structured intervention for most outcomes measures . CONCLUSIONS A behaviorally-based lifestyle intervention approach in which participants are taught behavioral skills to increase their physical activity by integrating moderate-intensity physical activity into their daily lives is more cost-effective than a structured exercise program in improving physical activity and cardiorespiratory health . This study represents one of the first attempts to compare the efficiency of intervention alternatives for improving physical activity among healthy , sedentary adults STUDY OBJECTIVES To determine whether long-term treatment with exercise therapy results in more favorable , disease-specific , health-related quality of life ( HRQL ) compared with short-term treatment with exercise therapy ; and to determine whether there are gender differences in disease-specific HRQL among individuals r and omized into the two treatment groups . DESIGN R and omized clinical trial . SETTING Center-based exercise therapy unit at a university . PARTICIPANTS One hundred forty patients with COPD ; 118 completed trial . INTERVENTIONS Short-term exercise therapy ( 3 months ) ; long-term exercise therapy ( 18 months ) . MEASUREMENTS Chronic Disease Respiratory Question naire ( CRQ ) . RESULTS After 3 months of treatment , there were significant improvements in all CRQ scores for men and women ( p < 0.01 ) , and for the total sample ( p < 0.01 ) . At 18 months , individuals r and omized into the long-term group had significantly more favorable scores than the short-term group for dyspnea ( p = 0.03 ) , fatigue ( p < 0.01 ) , emotional function ( p = 0.04 ) , and mastery ( p = 0.04 ) . However , these effects were moderated by gender . That is , men in the long-term group reported significantly more favorable scores than men in the short-term group for dyspnea ( 0.04 ) , fatigue ( p < 0.001 ) , emotional function ( p = 0.02 ) , and mastery ( p = 0.02 ) . At the 18-month assessment , there were no differences between long-term and short-term exercise therapy for women on any of the subscales of the CRQ . CONCLUSIONS Taken collectively , the CRQ data demonstrate that long-term exercise therapy has little added benefit for women over short-term exercise therapy ; however , men derive significant benefits from extended training Objectives 1 . To assess the long-term effectiveness of a comprehensive cardiac rehabilitation programme on quality of life and survival in patients with a large spectrum of cardiovascular diseases ( myocardial infa rct ion , acute coronary syndrome , percutaneous transluminal coronary angioplasty and coronary artery bypass grafting ) . 2 . To establish the degree of correlation between expected improvement of health-related quality of life and improvement in physical function attributable to rehabilitation in the intervention group , in comparison with similar changes in the conventional care group . Design R and omized , controlled , parallel-group design ( intervention/conventional care ) . Setting Akershus County , southeast of Oslo City , Norway . Participants 500 patients , men and women , aged 40 - 85 years , who have sustained at least one of the above-mentioned cardiovascular diseases . Interventions 8 weeks of supervised , structured physical training of three periods of 20 min per week , targeting a heart rate of 60 - 70 % of the individual 's maximum ; home-based physical exercise training with the same basic schedule as in the supervised period ; quantification of patients ' compliance with the exercise programme by the use of wristwatches , information Output:	Notably home based programs appeared to have a significantly higher adherence rate than center based programs . AUTHORS ' CONCLUSIONS In the short-term , center based programs are superior to home based programs in patients with PVD . There is a high possibility of a training effect however as the center based groups were trained primarily on treadmills ( and the home based were not ) and the outcome measures were treadmill based . There is conflicting evidence which is better in patients with COPD . Home based programs appear to be superior to center based programs in terms of the adherence to exercise ( especially in the long-term )
MS2790	*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 Increasing access to psychotherapy for posttraumatic stress disorder ( PTSD ) is a primary focus of the Department of Veterans Affairs ( VA ) healthcare system . Delivery of treatment via video telehealth can exp and availability of treatment and be equally effective as in-person treatment . Despite VA efforts , barriers to establishing telehealth services remain , including both provider acceptance and organizational obstacles . Thus , development of specific strategies is needed to implement video telehealth services in complex healthcare systems , like the VA . MATERIAL S AND METHODS This project was guided by the Promoting Action on Research Implementation in Health Services framework and used external facilitation to increase access to psychotherapy via video telehealth . The project was conducted at five VA Medical Centers and their associated community clinics across six states in the South Central United States . RESULTS Over a 21-month period , 27 video telehealth clinics were established to provide greater access to evidence -based psychotherapies for PTSD . Examination of change scores showed that participating sites averaged a 3.2-fold increase in unique patients and a 6.5-fold increase in psychotherapy sessions via video telehealth for PTSD . Differences between participating and nonparticipating sites in both unique patients and encounters were significant ( p=0.041 and p=0.009 , respectively ) . Two groups emerged , separated by degree of engagement in the facilitation intervention . Facilitation was perceived as useful by providers . CONCLUSIONS To our knowledge , this is the first prospect i ve study of external facilitation as an implementation strategy for telehealth . Our findings suggest that external facilitation is an effective and acceptable strategy to support providers as they establish clinics and make complex practice changes , such as implementing video telehealth to deliver psychotherapy Store- and -forward telepsychiatry , or asynchronous telepsychiatry ( ATP ) , which allows clinical data , including video to be collected to be review ed at a later time by a specialist , has been described as a feasible alternative to real-time telepsychiatry , or synchronous telepsychiatry ( STP ) , as a consultation model for primary care . In theory , ATP should be economically more cost-effective than STP due to the increased flexibility of patient data collection and the substitution of the time of specialists with that of lower-cost providers . The aim of this study was to conduct a retrospective cost- analysis comparing ATP with STP and traditional in-person psychiatric consultations in the primary care setting . One hundred and twenty five ATP consultations were performed and fixed and marginal costs were calculated for each model using inputs such as equipment costs , time spent by providers and support staff , and hourly salaries . The fixed costs were $ 7,000 and $ 20,000 for ATP and STP and marginal costs were $ 68.18 , $ 107.50 , and $ 96.36 , respectively , for the three groups . STP was the most expensive of the three types of consultations . ATP became the most cost-effective of the three models beyond 249 consultations . The marginal cost savings of ATP were due to substitution of low-cost providers for specialists . ATP represents a potential disruptive healthcare process that could allow more affordable care to be delivered to a larger population of patients . A full accounting of ATP 's efficiency will require further studies , including prospect i ve cost-benefit analyses from the perspectives of the patient , provider , and society The provision of mental health services via videoconferencing tele-mental health has become an increasingly routine component of mental health service delivery throughout the world . Emphasizing the research literature since 2003 , we examine : 1 ) the extent to which the field of tele-mental health has advanced the research agenda previously suggested ; and 2 ) implication s for tele-mental health care delivery for special clinical population s. Previous findings have demonstrated that tele-mental health services are satisfactory to patients , improve outcomes , and are probably cost effective . In the very small number of r and omized controlled studies that have been conducted to date , tele-mental health has demonstrated equivalent efficacy compared to face-to-face care in a variety of clinical setting s and with specific patient population s. However , method ologically flawed or limited research studies are the norm , and thus the research agenda for tele-mental health has not been fully maximized . Implication s for future research and practice are discussed Background : We conducted a r and omised study to investigate whether providing a self-guided Internet support group to cancer patients affected mood disturbance and adjustment to cancer . Methods : Baseline and 1- , 6- and 12-month assessment s were conducted from 2004 to 2006 at a national rehabilitation centre in Denmark . A total of 58 rehabilitation course weeks including 921 survivors of various cancers were r and omly assigned to a control or an intervention group by cluster r and omisation . The intervention was a lecture on the use of the Internet for support and information followed by participation in an Internet support group . Outcome measures included self-reported mood disturbance , adjustment to cancer and self-rated health . Differences in scores were compared between the control group and the intervention group . Results : The effect of the intervention on mood disturbance and adjustment to cancer showed a transient difference at the 6-month follow-up , where the intervention group reported less reduction in anxious preoccupation ( P=0.04 ) , helplessness ( P=0.002 ) , confusion ( P=0.001 ) and depression ( P=0.04 ) . Otherwise no significant effects were observed . Conclusion : We conclude that use of Internet-based support groups in cancer patients still needs to confirm long-lasting psychological effects BACKGROUND This study investigated the efficacy of an Internet-based self-help program with minimal therapist contact via e-mail for Swedish university students with social phobia and public speaking fears . The main objective was to test if the Internet-based self-help program would be more effective if five live group exposure sessions were added . METHODS Thirty-eight students meeting the diagnostic and statistical manual of mental disorders , 4th edition criteria for social phobia were r and omized into two different treatment groups : Internet delivered cognitive behavior therapy combined with five group exposure sessions ( ICBT+ exp ) or the Internet program alone ( ICBT ) . RESULTS Results were analyzed on an intention-to-treat basis . Both treatment groups showed significant improvement from pre- to post-test , and from pre-test to 1-year follow-up , on all measured dimensions ( social anxiety , general anxiety , depression levels , and quality of life ) . For both the groups , the average within-group effect sizes for the primary social anxiety scales , expressed as Cohen 's d , were comparable to those seen in traditionally administered cognitive behavioral therapy both at post-test and at 1- year follow-up . CONCLUSIONS The results suggest that the Internet-based self-help program on its own is efficient in the treatment of university students with social phobia . Adding group exposure sessions did not improve the outcome significantly Trends over the past decade have shown that online counseling has grown in terms of popularity among consumers and clinicians alike ; however , little , if any empirical evidence exists that examines client attitudes towards online counseling as alternative to traditional face-to-face therapy . Therefore , this study investigated client attitudes towards online counseling . Data was collected from 48 e-clients who received online counseling at the Center for Online Addiction . Variables such as client perceptions and concerns about using online counseling , clients ' reasons for seeking online counseling over in-office treatment , and demographic profiles of e-clients were assessed . Results suggested that Caucasian , middle-aged males , with at least a four-year bachelors degree were most likely to use online counseling and anonymity , convenience , and counselor credentials were the most cited reasons they sought online counseling over in-office treatment . The lack of perceived privacy and security during online chat sessions and the fear of being caught while conducting online sessions were the main concerns reported by e-clients . A better underst and ing of client motives and perceptions towards online counseling helps to guide treatment in using the Internet as a clinical tool , especially as the Internet becomes increasingly more available in previously remote markets and the field of online counseling continues to grow This method ological article provides a description of the design , methods , and rationale of the first prospect i ve , noninferiority design ed r and omized clinical trial evaluating the clinical and cost implication s of delivering an evidence -based cognitive-behavioral group intervention specifically treating posttraumatic stress disorder ( PTSD ) with a trauma-focused intervention via video teleconferencing ( VTC ) . PTSD is a prevalent mental health problem found among returning Operation Iraqi Freedom/Operation Enduring Freedom ( OIF/OEF ) military population s. These returning military personnel often live in rural areas and therefore have limited access to care and specialized psychological treatments . In the field of mental health , telemental health ( TMH ) technology has introduced a potential solution to the persistent problem of access to care in remote areas . This study is enrolling approximately 126 returning veterans with current combat-related PTSD who are receiving services through the Veteran Administration ( VA ) mental health care clinics on 4 Hawaiian Isl and s. Cognitive Processing Therapy ( CPT ) , an empirically supported manualized treatment for PTSD , is being delivered across 9 cohorts . Participants are assigned to either the experimental VTC condition or the in-person control condition . Assessment s measuring clinical , process , and cost outcomes are being conducted at baseline , mid-treatment , post-treatment , and 3 and 6 months post-treatment . The study employs a noninferiority design to determine if the group treatment delivered via VTC is as good as the traditional in-person modality . In addition , a cost analysis will be performed in order to compare the cost of the 2 modalities . Novel aspects of this trial and specific challenges are discussed Output:	Results : The findings revealed that telemental health care is an extended domain supportive of conventional mental health services . Currently , telemental health care has multiple capabilities and technologies for providing effective interventions to patients with various mental illnesses . It provides clinicians with a wide variety of innovative choices and strategies for mental interventions , in addition to significant future potentials . Conclusions : Telemental health care can provide effective and adaptable solutions to the care of mental illnesses universally . While being comparable to in-person services , telemental health care is particularly advantageous and inexpensive through the use of current technologies and adaptable design s , especially in isolated communities
MS2791	*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 " obesity paradox " is defined as an inverse association of good health , survival and obesity . Usually in healthy persons the more obese you are the more metabolic complications you have ; however , thin patients with chronic obstructive pulmonary disease ( COPD ) have more cardiovascular complications and a higher mortality rate . OBJECTIVES To explore whether atherosclerosis and peripheral artery disease ( PAD ) contribute to the higher morbidity and mortality of patients with COPD . METHODS This prospect i ve study included 87 patients with chronic COPD who were treated in the pulmonary outpatient clinic ; all signed a consent form before enrollment . We documented their lung function ( FEV1 % ) , body mass index ( BMI ) and ankle brachial index ( ABI ) . The primary endpoints were to find an association between atherosclerosis and BMI in patients with COPD , and between atherosclerosis and severity of lung disease . RESULTS Average ABI was 1.01 + /- 0.20 , BMI was 29.33 + /- 7.48 kg/m2 , and the abdominal circumference was 107.34 + /- 18.87 cm . A positive correlation was found between BMI and ABI ( P=0.001 ) and between abdominal circumference and ABI ( P=0.000 ) . Patients with peripheral artery disease were older ( 73.6 + /- 11.5 vs. 68.1 + /- 11.6 years old , P= 0.04 ) , were thinner ( average BMI 25.5 + /- 6.2 vs. 31.06 + /- 7.3 , P= 0.001 ) , and had a lower abdominal circumference ( 97.7 + /- 18.3 vs. 111.7 + /- 17.5 cm , P=0.001 ) . No such difference was observed for years of smoking . Male PAD patients with COPD had a lower BMI ( 25.2 + /- 5.6 vs. 29.9 + /- 7.4 , P = 0.016 ) , and their abdominal circumference was smaller ( 96.1 + /- 18.0 vs. 110.2 + /- 16.5 cm , P=0.004 ) . Female PAD patients with COPD had a lower BMI ( 26.3 + /- 8.2 vs. 33.1 + /- 7.0 , P=0.045 ) , but their abdominal circumference was not different from females without PAD ( 102.0 + /- 19.7 vs. 114.0 + /- 19.4 cm , P=0.162 ) . Patients with PAD had a worse lung disease ( FEV1 % 34 + /- 8 % vs. 45 + /- 16 % , P=0.01 ) . During the 1 year of follow-up five patients died : two PAD patients due to acute myocardial infa rct ion and three non-PAD patients died from pulmonary insufficiency ( two patients ) and pulmonary emboli ( one patient ) . DISCUSSION We found that COPD patients with PAD were older and thinner and had a lower abdominal circumference and a more progressive lung disease . Extensive atherosclerosis in patients with COPD may partly explain the " obesity paradox " observed in patients with COPD Background The association between change in weight or body mass index , and mortality is widely reported , however , both measures fail to account for fat distribution . Change in waist circumference , a measure of central adiposity , in relation to mortality has not been studied extensively . Methods We investigated the association between mortality and changes in directly measured waist circumference , hips circumference and weight from baseline ( 1990–1994 ) to wave 2 ( 2003–2007 ) in a prospect i ve cohort study of people aged 40–69 years at baseline . Cox regression , with age as the time metric and follow-up starting at wave 2 , adjusted for confounding variables , was used to estimate hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) for change in body size in relation to mortality from all causes , cardiovascular disease and cancer . Results There were 1465 deaths ( 109 cancer , 242 cardiovascular disease ) identified during an average 7.7 years of follow-up from 21 298 participants . Compared to minimal increase in body size , loss of waist circumference ( HR : 1.26 ; 95 % CI : 1.09–1.47 ) , weight ( 1.80 ; 1.54–2.11 ) , or hips circumference ( 1.35 ; 1.15–1.57 ) were associated with an increased risk of all-cause mortality , particularly for older adults . Weight loss was associated with cardiovascular disease mortality ( 2.40 ; 1.57–3.65 ) but change in body size was not associated with obesity-related cancer mortality . Conclusion This study confirms the association between weight loss and increased mortality from all-causes for older adults . Based on evidence from observational cohort studies , weight stability may be the recommended option for most adults , especially older adults Conflicting results have been reported concerning the association between body weight and longevity . The shape of the curve relating weight to all-cause mortality has been variously described as linear , J-shaped , and even U-shaped . To assess the validity of the evidence for optimal weight recommendations , we examined the 25 major prospect i ve studies on the subject . Each study had at least one of three major biases : failure to control for cigarette smoking , inappropriate control of biologic effects of obesity , such as hypertension and hyperglycemia , and failure to control for weight loss due to sub clinical disease . The presence of these biases leads to a systematic underestimate of the impact of obesity on premature mortality . Although these biases preclude a valid assessment of optimal weight from existing data , available evidence suggests that minimum mortality occurs at relative weights at least 10 % below the US average BACKGROUND AND OBJECTIVES A high body mass index ( BMI ) is associated with lower mortality in patients undergoing hemodialysis . Short-term weight gains and losses are also related to lower and higher mortality risk , respectively . The implication s of weight gain or loss may , however , differ between obese individuals and their nonobese counterparts . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS The Current Management of Secondary Hyperparathyroidism : A Multicenter Observational Study ( COSMOS ) is an observational study including 6797 European hemodialysis patients recruited between February 2005 and July 2007 , with prospect i ve data collection every 6 months for 3 years . Time-dependent Cox proportional hazard regressions assessed the effect of BMI and weight changes on mortality . Analyses were performed after patient stratification according to their starting BMI . RESULTS Among 6296 patients with complete data , 1643 died . At study entry , 42 % of patients had a normal weight ( BMI , 20 - 25 kg/m(2 ) ) , 11 % were underweight , 31 % were overweight , and 16 % were obese ( BMI ≥ 30 kg/m(2 ) ) . Weight loss or gain ( < 1 % or > 1 % of body weight ) was strongly associated with higher rates of mortality or survival , respectively . After stratification by BMI categories , this was true in nonobese categories and especially in underweight patients . In obese patients , however , the association between weight loss and mortality was attenuated ( hazard ratio , 1.28 [ 95 % confidence interval ( CI ) , 0.74 to 2.14 ] ) , and no survival benefit of gaining weight was seen ( hazard ratio , 0.98 [ 95 % CI , 0.59 to 1.62 ] ) . CONCLUSIONS Assuming that these weight changes were unintentional , our study brings attention to rapid weight variations as a clinical sign of health monitoring in hemodialysis patients . In addition , a patient 's BMI modifies the strength of the association between weight changes with mortality BACKGROUND Although weight loss reduces risk for comorbid diseases , many observational studies suggest that weight loss is associated with increased mortality risk , leading to reluctance by clinicians to consider weight reduction as a strategy to maintain health and independence in older adults . However , whether the observed weight loss is intentional is difficult to determine and may not accurately represent the mortality risk associated with intentional weight reduction . Data from the Arthritis , Diet , and Activity Promotion Trial ( ADAPT ) were used to determine whether r and omization to a weight reduction program was associated with total mortality in overweight/obese older adults . METHODS ADAPT ( n = 318 ; mean age 69 + /- 6 years , body mass index 34 + /- 5 kg/m2 , 72 % female ) assessed the influence of weight loss ( achieved through dietary counseling and lifestyle modification ) and /or exercise on function in overweight/obese older adults with knee osteoarthritis . ADAPT ended in December 1999 . Participant vital was ascertained status through December 2006 using the National Death and Social Security Indexes . RESULTS The mortality rate for those r and omized to the 18-month weight loss intervention ( n = 159 , mean weight loss = -4.8 kg , 15 deaths ) was lower than that for those not r and omized to the weight loss intervention ( n = 159 , mean weight loss = -1.4 kg , 30 deaths ; hazard rate ratio = 0.5 , 95 % confidence interval 0.3 - 1.0 ) . Results were not appreciably changed when analyses were stratified by age , gender , baseline weight status , or magnitude of weight loss . CONCLUSIONS In older adults , intentional weight loss was not associated with increased total mortality and may reduce mortality risk . Observational studies of weight loss , especially when intentionality can not be rigorously established , may be misleading with respect to the effect of weight loss on mortality Although 25 % of US men indicate that they are trying to lose weight , the association between intentional weight loss and longevity in men is unknown . The authors analyzed prospect i ve data from 49,337 overweight ( initial body mass index > or = 27 ) white men aged 40 - 64 years who , in 1959 - 1960 , answered questions on weight change direction , amount , time interval , and intent . Vital status was determined in 1972 . Proportional hazards regression estimated mortality rate ratios for men who intentionally lost weight compared with men with no weight change . Analyses were stratified by health status and adjusted for age , initial body mass index , smoking status , alcohol intake , education , physical activity , health history , and physical symptoms . Among men with no reported health conditions ( n = 36,280 ) , intentional weight loss was not associated with total , cardiovascular ( CVD ) , or cancer mortality , but diabetes-associated mortality was increased 48 % ( 95 % confidence interval ( CI ) -7 % to + 133 % ) among those who lost 20 pounds ( 9.1 kg ) or more ; this increase was largely related to non-CVD mortality . Among men with reported health conditions ( n = 13,057 ) , intentional weight loss had no association with total or CVD mortality , but cancer mortality increased 25 % ( 95 % confidence interval -4 % to + 63 % ) among those who lost 20 pounds or more . Diabetes-associated mortality was reduced 32 % ( 95 % confidence interval -52 % to -5 % ) among those who lost less than 20 pounds and 36 % ( 95 % confidence interval -49 % to -20 % ) among those who lost more than 20 pounds . These results and those from our earlier study in women ( Williamson et al. , Am J Epidemiol 1995;141:1128 - 41 ) suggest that intentional weight loss may reduce the risk of dying from diabetes , but not from CVD . In observational studies , however , it is difficult to separate intentional weight loss from unintentional weight loss due to undiagnosed , underlying disease . Well- design ed observational studies , as well as r and omized controlled trials , are needed to determine whether intentional weight loss reduces CVD mortality The relation between relative weight and health differs between young and old . In older population s , weight change may cloud the association between a single relative weight and health outcomes . To determine whether weight or weight change is a more important determinant of mortality in a population of older adults , the authors analyzed data from the Systolic Hypertension in the Elderly Program ( 1984 - 1990 ) , a r and omized clinical trial testing the efficacy of antihypertensive drug treatment to reduce the risk of stroke in older adults ( aged 60 years or more ) with isolated systolic hypertension . After adjustment for covariates , an average annualized weight loss of at least 1.6 kg/year ( odds ratio = 4.9 ) , a weight loss between 1.6 and 0.7 kg/year ( odds ratio = 1.7 ) , a weight gain of more than 0.5 kg/year ( odds ratio = 2.4 ) , and a baseline body mass index of less than 23.6 ( odds ratio = 1.4 ) all had a significant ( p < 0.05 ) association with all-cause mortality compared with a referent group that was weight stable and of intermediate body mass index ( 23.6 to < 28.0 kg/m(2 ) ) and weight change ( -0.7 to < 0.5 kg/year ) . The authors Output:	Unintentional weight loss had a significant impact on all-cause mortality . We found no protective effect of being overweight or obese for unintentional weight loss and MACE
MS2792	*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 this paper are reported the basal results of a multidisciplinary , multicenter study design ed to explore in a population with ischemic disease the relation between hemostatic variables , conventional risk factors and atherothrombotic sequelae . 953 patients less than or equal to 69 yrs with documented coronary , cerebral or peripheral atherosclerotic disease were studied and followed-up for 24 months . Examinations included hemostatic and lipid laboratory assays , arterial Doppler examination , cerebral computerized tomography and nuclear magnetic resonance , exercise electrocardiogram and coronary angiography . Fibrinogen ( 301.4 + /- 71.52 mg/dl ) correlated positively with antithrombin III ( r = 0.27 ) and leukocytes ( r = 0.25 ) , negatively with HDL-cholesterol ( r = 0.18 ) and tended to increase with smoking . Heavy smokers had higher leukocyte counts than non-smokers ( 8.0 + /- 2.0 vs. 7.2 + /- 2.1 x 10(3)/microliters ) , higher triglycerides ( 1.87 + /- 1.12 vs. 1.53 + /- 1.35 mmol/l ) and lower HDL-cholesterol ( 0.93 + /- 0.27 vs. 1.00 + /- 0.25 mmol/l ) . FVII correlated positively with triglycerides ( r = 0.16 ) and protein C ( r = 0.45 ) . vWF : Ag ( 145.4 + /- 70.58 % ) ad FVII : C ( 139.7 + /- 59.10 % ) were positively correlated ( r = 0.44 ) . FVIII : C correlated positively with fibrinogen ( r = 0.21 ) . Myocardial infa rct ion survivors with associated cerebral and peripheral vascular lesions had higher FVIII : C , FVII , fibronogen and vWF : Ag . These findings suggest that hemostatic factors may enhance and /or mediate the effects of conventional risk factors in atherothrombotic ischemic events BACKGROUND AND METHODS The use of oral anticoagulation in the long-term treatment of survivors of acute myocardial infa rct ion has been highly controversial . We therefore r and omly assigned 1214 patients who had recovered from acute myocardial infa rct ion ( mean interval from the onset of symptoms to r and omization , 27 days ) to treatment with warfarin ( 607 patients ) or placebo ( 607 patients ) for an average of 37 months ( range , 24 to 63 ) . RESULTS At the end of the treatment period , there had been 123 deaths in the placebo group and 94 in the warfarin group -- a reduction in risk of 24 percent ( 95 percent confidence interval , 4 to 44 percent ; P = 0.027 ) . A total of 124 patients in the placebo group had reinfa rct ions , as compared with 82 in the warfarin group -- a reduction of 34 percent ( 95 percent confidence interval , 19 to 54 percent ; P = 0.0007 ) . Furthermore , we observed a reduction of 55 percent ( 95 percent confidence interval , 30 to 77 percent ) in the number of total cerebrovascular accidents in the warfarin group as compared with the placebo group ( 44 vs. 20 ; P = 0.0015 ) . Serious bleeding was noted in 0.6 percent of the warfarin-treated patients per year . CONCLUSIONS Long-term therapy with warfarin has an important beneficial effect after myocardial infa rct ion and can be recommended in the treatment of patients who survive the acute phase Background —Reinfa rct ion after primary percutaneous coronary intervention in patients with ST-segment – elevation myocardial infa rct ion has negative consequences . Little is known about reinfa rct ion after drug-eluting stents and bivalirudin anticoagulation . We , therefore , sought to determine the incidence , predictors , and implication s of reinfa rct ion after primary percutaneous coronary intervention in the contemporary era . Methods and Results — Outcomes were assessed in 3202 patients undergoing stent implantation for ST-segment – elevation myocardial infa rct ion in the Harmonizing Outcomes with RevascularIZatiON and Stents in Acute Myocardial Infa rct ion ( HORIZONS-AMI ) trial . Independent predictors of reinfa rct ion and mortality were identified by Cox proportional hazards modeling . The cumulative incidence of reinfa rct ion was 1.8 % at 30 days , 4.0 % at 1 year , and 6.9 % at 3 years . Definite stent thrombosis was responsible for 76.3 % of reinfa rct ions occurring within 30 days and 52.0 % of all reinfa rct ions within 3 years . Independent predictors of reinfa rct ion were current smoking , Killip class ≥2 , baseline thrombocytosis , multivessel disease , symptom onset-to-balloon time , and total stent length . R and omization to bivalirudin versus heparin plus a glycoprotein IIb/IIIa inhibitor and use of drug-eluting versus bare metal stents were not significant predictors of reinfa rct ion . Reinfa rct ion was a powerful independent predictor of subsequent cardiac mortality ( hazard ratio [ 95 % confidence interval]=7.65 [ 4.47–13.09 ] ; P<0.0001 ) and all-cause mortality ( hazard ratio [ 95 % confidence interval]=2.88 [ 1.74–4.78 ] ; P<0.0001 ) . Conclusions —Despite advances in pharmacotherapy and stents , reinfa rct ion after primary percutaneous coronary intervention is not infrequent , in the contemporary era is most often attributable to stent thrombosis , and is strongly associated with subsequent cardiac and all-cause mortality . Further enhancements in drugs and devices to prevent reinfa rct ion are needed to improve outcomes in high-risk patients with ST-segment – elevation myocardial infa rct ion . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NCT00433966 OBJECTIVES --To assess the incidence and significance of anticardiolipin antibodies after myocardial infa rct ion and in unstable angina . DESIGN --A prospect i ve study of all patients under 60 admitted to the coronary care unit over a 12 month period with a diagnosis of acute myocardial infa rct ion who were followed up for a further 12 months . Patients admitted with unstable angina were similarly assessed but not followed up . Anticardiolipin antibody concentrations were compared with those of age matched controls . SETTING --A district general hospital . PATIENTS --307 patients with acute myocardial infa rct ion and 160 patients with unstable angina . RESULTS --Anticardiolipin antibody concentrations in the two patient groups did not differ significantly from those in the control groups . Antibody concentrations were not related to a history of angina or myocardial infa rct ion nor were they related to subsequent cardiovascular complications . CONCLUSION --This study shows no significant association between anticardiolipin antibody concentrations and either myocardial infa rct ion or unstable angina Antiphospholipid antibodies have been suggested as markers for a high risk of recurrent cardiovascular events in young survivors of an acute myocardial infa rct ion . However , there are few data to confirm or refute this hypothesis . In a cohort study , we have measured anticephalin ( aCEPHA ) and anticardiolipin ( aCL ) antibodies in a group of patients surviving an acute infa rct . Of 597 patients studied , 13.2 % were IgG or IgM aCEPHA positive compared with 4.4 % of a reference population ( n = 158 ; p = 0.002 ) . In a multivariate analysis , adjusted for major cardiovascular risk factors , neither aCEPHA ( IgG or IgM ) nor a CL ( IgG or IgM ) was an independent risk factor for mortality , reinfa rct ion , or non-haemorrhagic stroke . Although an increased proportion of survivors of a myocardial infa rct ion have antiphospholipid antibodies , the presence of such antibodies is not a risk factor for subsequent coronary or cerebrovascular thrombosis BACKGROUND Acute coronary syndromes arise from coronary atherosclerosis with superimposed thrombosis . Since factor Xa plays a central role in thrombosis , the inhibition of factor Xa with low-dose rivaroxaban might improve cardiovascular outcomes in patients with a recent acute coronary syndrome . METHODS In this double-blind , placebo-controlled trial , we r and omly assigned 15,526 patients with a recent acute coronary syndrome to receive twice-daily doses of either 2.5 mg or 5 mg of rivaroxaban or placebo for a mean of 13 months and up to 31 months . The primary efficacy end point was a composite of death from cardiovascular causes , myocardial infa rct ion , or stroke . RESULTS Rivaroxaban significantly reduced the primary efficacy end point , as compared with placebo , with respective rates of 8.9 % and 10.7 % ( hazard ratio in the rivaroxaban group , 0.84 ; 95 % confidence interval [ CI ] , 0.74 to 0.96 ; P=0.008 ) , with significant improvement for both the twice-daily 2.5-mg dose ( 9.1 % vs. 10.7 % , P=0.02 ) and the twice-daily 5-mg dose ( 8.8 % vs. 10.7 % , P=0.03 ) . The twice-daily 2.5-mg dose of rivaroxaban reduced the rates of death from cardiovascular causes ( 2.7 % vs. 4.1 % , P=0.002 ) and from any cause ( 2.9 % vs. 4.5 % , P=0.002 ) , a survival benefit that was not seen with the twice-daily 5-mg dose . As compared with placebo , rivaroxaban increased the rates of major bleeding not related to coronary-artery bypass grafting ( 2.1 % vs. 0.6 % , P<0.001 ) and intracranial hemorrhage ( 0.6 % vs. 0.2 % , P=0.009 ) , without a significant increase in fatal bleeding ( 0.3 % vs. 0.2 % , P=0.66 ) or other adverse events . The twice-daily 2.5-mg dose result ed in fewer fatal bleeding events than the twice-daily 5-mg dose ( 0.1 % vs. 0.4 % , P=0.04 ) . CONCLUSIONS In patients with a recent acute coronary syndrome , rivaroxaban reduced the risk of the composite end point of death from cardiovascular causes , myocardial infa rct ion , or stroke . Rivaroxaban increased the risk of major bleeding and intracranial hemorrhage but not the risk of fatal bleeding . ( Funded by Johnson & Johnson and Bayer Healthcare ; ATLAS ACS 2-TIMI 51 Clinical Trials.gov number , NCT00809965 . ) CONTEXT The presence of antiphospholipid antibodies ( aPL ) has been associated with vascular occlusive events . However , the role of aPL in predicting ischemic events , particularly recurrent ischemic stroke , is controversial . OBJECTIVE To evaluate the effect of baseline aPL positivity ( ie , positivity for anticardiolipin antibodies [ aCL ] , lupus anticoagulant antibodies [ LA ] , or both ) on subsequent thrombo-occlusive events , including recurrent stroke . DESIGN , SETTING , AND PARTICIPANTS The Antiphospholipid Antibodies and Stroke Study ( APASS ) , a prospect i ve cohort study within the Warfarin vs Aspirin Recurrent Stroke Study ( WARSS ) , a r and omized double-blind trial ( N = 2206 ) conducted at multiple US clinical sites from June 1993 through June 2000 and comparing adjusted-dose warfarin ( target international normalized ratio , 1.4 - 2.8 ) and aspirin ( 325 mg/d ) for prevention of recurrent stroke or death . APASS participants were 1770 ( 80 % ) WARSS participants who consented to enroll in the APASS , with usable baseline blood sample s drawn prior to r and omization to the WARSS and analyzed for aPL status within 90 days of index stroke by a central independent laboratory . Quality assurance was performed on approximately 10 % of sample s by a second independent laboratory . MAIN OUTCOME MEASURE Two-year rate of the composite end point of death from any cause , ischemic stroke , transient ischemic attack , myocardial infa rct ion , deep vein thrombosis , pulmonary embolism , and other systemic thrombo-occlusive events . The primary analysis assessed the outcome associated with aPL positivity within each WARSS treatment group separately , after risk-factor adjustment ( since these aPL Output:	CONCLUSION Patients with CAD and elevated IgG aCL have a doubled risk of recurrent MACE at 12 and 24 months .
MS2793	*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: Managing children with influenza-like illness is associated with costly and painful interventions because , in order to distinguish viral from bacterial infections , diagnostic tests ( including routine blood examinations and chest radiographs ) are frequently performed,1,2 and the empirical use of antimicrobial agents is common.3 Various rapid diagnostic techniques for the detection of influenza viruses have been developed , but few data are available on their impact on child care.2,4,5 The aim of this study was to assess the effect of a rapid diagnosis of influenza infection on the management of children with influenza-like illness in an emergency department . All patients seen for influenza-like illness from 6 January to 27 February 2002 , at the paediatric emergency department of the University of Milan , Italy , were enrolled and blindly r and omly assigned in a 1:1 ratio to undergo a rapid test for the detection of influenza viruses or no rapid test . Influenza-like illness was defined as an axillary temperature of ⩾37.8 ° C and at least one symptom of acute upper or lower respiratory tract disease.6 The patients who underwent the test had their throats swabbed after vigorously rubbing both tonsillar surfaces and the posterior pharynx ; the swab was then immediately su bmi tted to the Quickvue influenza test ( Quidel , Milan , Italy ) for the rapid detection of influenza A and B viruses . The test , which has an overall sensitivity of 74–95 % and an overall specificity of 76–98%,5,7,8 was performed by a postgraduate student in accordance with the manufacturer ’s recommendations . The results were available after 10 Recent empirical evidence supports the importance of adequate r and omization in controlled trials . Trials with inadequate allocation concealment have been associated with larger treatment effects compared with trials in which authors reported adequate allocation concealment . While that provides empirical evidence of bias being interjected into trials , trial investigators rarely document the sensitive details of subverting the intended purpose of r and omization . This article relates anonymous accounts run the gamut from simple to intricate operations , from transillumination of envelopes to search ing for code in the office files of the principal investigator . They indicate that deciphering is something more frequent than a rate occurrence . These accounts prompt some method ological recommendations to help prevent deciphering . R and omized controlled trials appear to annoy human nature -- if properly conducted , indeed they should OBJECTIVE To determine the impact of the rapid diagnosis of influenza on physician decision-making and patient management , including laboratory tests and radiographs ordered , patient charges associated with these tests , antibiotics/antivirals prescribed , and length of time to patient discharge from the emergency department . METHODS Patients aged 2 months to 21 years presenting to an urban children 's teaching hospital emergency department were screened for fever and cough , coryza , myalgias , headache , and /or malaise . After obtaining informed consent , patients were r and omized to 1 of 2 groups : 1 ) physician receives ( physician aware of ) the rapid influenza test result ; or 2 ) physician does not receive ( physician unaware of ) the result . For patients in the physician aware group , nasopharyngeal swabs were obtained , immediately tested with the FluOIA test for influenza A and B , and the result was placed on the chart before patient evaluation by the attending physician . For the physician unaware group , nasopharyngeal swabs were obtained , stored according to manufacturer 's directions , and tested within 24 hours . Results for the physician unaware group were not disclosed to the treating physicians at any time . The 2 result ant influenza-positive groups ( aware and unaware ) were compared for laboratory and radiograph studies and their associated patient charges , antibiotic/antiviral prescriptions , and length of stay in the emergency department . RESULTS A total of 418 patients were enrolled , and 391 completed the study . Of these , 202 tested positive for influenza . Comparison of the 96 influenza-positive patients whose physician was aware of the result with the 106 influenza-positive patients whose physician was unaware of the result revealed significant reductions among the former group in : 1 ) numbers of complete blood counts , blood cultures , urinalyses , urine cultures , and chest radiographs performed ; 2 ) charges associated with these tests ; 3 ) antibiotics prescribed ; and 4 ) length of stay in the emergency department . The number of influenza-positive patients who received prescriptions for antiviral drugs was significantly higher among those whose physician was aware of the result . CONCLUSIONS Physician awareness of a rapid diagnosis of influenza in the pediatric emergency department significantly reduced the number of laboratory tests and radiographs ordered and their associated charges , decreased antibiotic use , increased antiviral use , and decreased length of time to discharge OBJECTIVES Acute respiratory tract infections represent a significant burden on pediatric emergency departments ( ED ) and families . We hypothesized that early and rapid diagnosis of a viral infection alleviates the need for ancillary testing and antibiotic treatment . STUDY DESIGN We conducted a r and omized , controlled trial of children 3 to 36 months of age with febrile acute respiratory tract infections at a pediatric ED . Two hundred four subjects were r and omly assigned to receive rapid respiratory viral testing on admission or a routine ED admission protocol . Outcome measures were : mean length of visits , rate of ancillary tests , and antibiotic prescription in the ED . A follow-up call was made to all study subjects to inquire about further healthcare visits , ancillary testing , and antibiotic prescription after ED discharge . RESULTS We did not find a statistically significant difference in ED length of visits , rate of ancillary testing , or antibiotic prescription rate in the ED between the study groups . There was , however , a significant reduction in antibiotic prescription after ED discharge ( in the group who had rapid viral testing RR = 0.36 ; 95 % CI = 0.14 , 0.95 ) . CONCLUSIONS Rapid multi-viral testing in the ED did not significantly affect ED patient treatment but may reduce antibiotic prescription in the community after discharge from the ED , suggesting a novel strategy to alter community physician antibiotic prescription patterns BACKGROUND Evidence shows that the rapid detection of influenza using an enzyme-linked immunosorbent assay decreases antibiotic use in the treatment of pediatric patients . To our knowledge , the effect on other diagnostic testing in an emergency department ( ED ) has not been examined . OBJECTIVE To determine the effect of rapid diagnosis of influenza virus type A on the clinical management of febrile infants and toddlers in a pediatric ED at an urban children 's hospital . MATERIAL S AND METHODS A retrospective review of ED records from an electronic data base was performed . All children 2 to 24 months of age , with a temperature higher than 39 degrees C who had a positive influenza virus type A test result using an enzyme-linked immunosorbent assay from November 1 , 1998 , through April 30 , 2000 ( n = 72 ) , were included in this study . Two groups were compared-those who had positive test results reported before discharge from the ED ( early diagnosis ) and those who had positive test results after discharge ( late diagnosis ) . RESULTS Forty-seven patients ( 65 % ) were in the early diagnosis group and 25 ( 35 % ) in the late diagnosis group . The groups were similar for age , temperature , and triage category . Fewer patients in the early diagnosis group received ceftriaxone sodium compared with those in the late diagnosis group ( 2 % vs 24 % , P = .006 ) ; there were fewer urinalyses ( 2 % vs 24 % , P = .006 ) and complete blood cell counts performed ( 17 % vs 44 % , P = .02 ) . CONCLUSIONS Rapid confirmation of influenza virus type A infection seems to decrease ancillary tests and antibiotic use in febrile infants and toddlers in the ED . A prospect i ve study with a larger group is needed to confirm these findings BACKGROUND The evaluation of young febrile infants is controversial , in part because it is unclear whether clinical evidence of a viral infection significantly reduces the risk of serious bacterial infections ( SBIs ) . Specifically , it remains unclear whether the risk of SBI is altered in a meaningful way in the presence of respiratory syncytial virus ( RSV ) infections . OBJECTIVE The objective of this study was to determine the risk of SBI in young febrile infants who are infected with RSV compared with those without RSV infections . METHODS We conducted a 3-year multicenter , prospect i ve , cross-sectional study . All febrile ( > or = 38 degrees C ) infants who were < or = 60 days of age and presented to any of 8 pediatric emergency departments from October through March 1998 - 2001 were eligible . General clinical appearance was evaluated using the Yale Observational Scale . We determined RSV status by antigen testing of nasopharyngeal secretions . We defined bronchiolitis as either wheezing alone or chest retractions in association with an upper respiratory infection . We evaluated infants with blood , urine , cerebrospinal fluid , and stool cultures . Urinary tract infection ( UTI ) was defined by single pathogen growth of > or = 5 x 10(4 ) cfu/mL , or > or = 10(4 ) cfu/mL in association with a positive urinalysis in a catheterized specimen , or > or = 10(3 ) cfu/mL in a suprapubic aspirate . Bacteremia , bacterial meningitis , and bacterial enteritis were defined by growth of a known bacterial pathogen . SBI was defined as any of the above-mentioned 4 bacterial infections . RESULTS We enrolled 1248 patients , including 269 ( 22 % ) with RSV infections . The overall SBI status could be determined in 1169 ( 94 % ) of the 1248 patients , and the rate of SBIs was 11.4 % ( 133 of 1169 ; 95 % confidence interval [ CI ] : 9.6%-13.3 % ) . The rate of SBIs in the RSV-positive infants was 7.0 % ( 17 of 244 ; 95 % CI : 4.1%-10.9 % ) compared with 12.5 % ( 116 of 925 ; 95 % CI : 10.5%-14.8 % ) in the RSV-negative infants ( risk difference : 5.5 % ; 95 % CI : 1.7%-9.4 % ) . The rate of UTI in the RSV-positive infants was 5.4 % ( 14 of 261 ; 95 % CI : 3.0%-8.8 % ) compared with 10.1 % ( 98 of 966 ; 95 % CI : 8.3%-12.2 % ) in the RSV-negative infants ( risk difference : 4.7 % ; 95 % CI : 1.4%-8.1 % ) . The RSV-positive infants had a lower rate of bacteremia than the RSV-negative infants ( 1.1 % vs 2.3 % ; risk difference : 1.2 % ; 95 % CI : -0.4 % to 2.7 % ) . No RSV-positive infant had bacterial meningitis ( 0 of 251 ; 95 % CI : 0%-1.2 % ) ; however , the differences between the 2 groups with regard to bacteremia and bacterial meningitis did not achieve statistical significance . CONCLUSIONS Febrile infants who are < or = 60 days of age and have RSV infections are at significantly lower risk of SBI than febrile infants without RSV infection . Nevertheless , the rate of SBIs , particularly as a result of UTI , remains appreciable in febrile RSV-positive infants OBJECTIVES To determine the effect of point-of-care testing ( POCT ) for influenza on the physician management of febrile children who are at risk for serious bacterial illness ( SBI ) on the basis of age and temperature and who are presenting to a pediatric emergency department ( ED ) during an influenza outbreak . METHODS Patients 2 - 3 months of age with temperature of > or = 38 degrees C and patients 3 - 24 months of age with temperature of > or = 39 degrees C who were presenting to a pediatric ED during an influenza outbreak were enrolled into a prospect i ve , quasi-r and omized , controlled trial . Influenza testing was performed on enrolled patients by either the POCT or the st and ard-testing ( ST ) methods . The two groups were compared in terms of laboratory testing , chest radiography , antibiotic use , visit-associated costs , pediatric ED lengths of stay , inpatient admission , and return visits to the pediatric ED . Similar analyses also were performed on the result ing subgroups of patients on the basis of method of testing ( POCT or ST ) and test result ( positive or negative ) . RESULTS Of 767 eligible patients , 700 ( 91 % ) completed the study . No significant differences were demonstrated between the POCT and ST groups with respect to laboratory tests ordered , chest radiographs obtained , antibiotic administration , inpatient admission , return visits to the pediatric ED , lengths of stay , or visit-associated costs . In the subgroup analysis , the adjusted odds ratios ( ORs ) for blood culture in influenza test-positive to -negative patients were 0.59 and 0.71 in the POCT and ST groups , respectively ( p = 0.088 ) . The adjusted ORs for urine culture in influenza test-positive to -negative patients were 0.46 and 0 Output:	None of the studies definitively blinded participants .Rapid viral testing result ed in a trend toward decreased antibiotic use in the ED , but this was not statistically significant . There is insufficient evidence to support routine rapid viral testing to reduce antibiotic use in pediatric EDs . However , rapid viral testing does reduce the rate of chest X-rays in the ED .
MS2794	*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 We examined the metabolic , performance and gastrointestinal ( GI ) effects of supplementation with a natural food product ( raisins ) compared to a commercial product ( sport chews ) . Methods Eleven male ( 29.3 ± 7.9 yrs ; mean and SD ) runners completed three r and omized trials ( raisins , chews and water only ) separated by seven days . Each trial consisted of 80-min ( 75%VO2max ) treadmill running followed by a 5-km time trial ( TT ) . Heart rate ( HR ) , respiratory exchange ratio ( RER ) , blood lactate , serum free fatty acids ( FFA ) , glycerol and insulin , plasma glucose and creatine kinase , GI symptoms and rating of perceived exertion ( RPE ) were recorded every 20-min . We employed a within-subject two-way analysis of variance ( ANOVA ) for repeated measures with a Fisher ’s post hoc analysis to determine significant differences . Results VO2 , HR , lactate , glycerol and RPE did not differ due to treatment . Average plasma glucose was maintained at resting levels ( 5.3 ± 0.4 mmol·L-1 ) during the sub-maximal exercise bout ( 5.9 ± 0.6 , 5.7 ± 0.6 and 5.5 ± 0.5 mmol·L-1 for chews , raisins and water respectively ) , and was significantly higher with chews than water only . RER and % of non-protein macronutrient oxidation derived from carbohydrate was highest with chews , followed by raisins and water was the lowest ( 74.4 ± 6.4 , 70.0 ± 7.0 and 65.1 ± 8.7 % for chews , raisins and water respectively ) during the sub-maximal exercise period . Serum FFA was higher in the water treatment versus both raisins and chews at 80 min of sub-maximal exercise . Serum insulin was higher with the chews than both raisins and water ( 5.1 ± 2.0 , 3.1 ± 0.8 , 1.9 ± 0.6 uU·ml-1 for chews , raisins and water respectively ) . Plasma creatine kinase , corrected for baseline values , for the last 40 min of the sub-maximal exercise bout , was higher with raisins compared to other treatments . The TT was faster for both carbohydrate supplements ( 20.6 ± 2.6 , 20.7 ± 2.5 , 21.6 ± 2.7 min for raisin , chews and water respectively ) . GI disturbance was mild for all treatments . Conclusion Raisins and chews promoted higher carbohydrate oxidation and improved running performance compared to water only . Running performance was similar between the raisins and chews , with no significant GI differences On three occasions cyclists completed , as fast as possible , two exercise tasks ( T1 and T2 ) separated by 30 min rest . T1 and T2 were equivalent to the work performed during 2 h cycling at 75 % VO2max and 30 min at 75 % VO2max , respectively . Every 20 min subjects drank 275 mL of a 6 % ( MC ) or 2.5 % ( LC ) carbohydrate-electrolyte beverage or a water placebo ( P ) . The initial drink during both T1 and the rest period contained 20 g D2O as a marker for entry of ingested fluid into blood . No differences in drink effects were found for heart rate , sweat rate , change in plasma volume , rectal temperature , or D2O accumulation in blood . Blood glucose and respiratory exchange ratios were higher and T2 was performed faster with MC than with P. Ingestion of MC can help maintain blood glucose and enhance performance of prolonged cycling exercise without compromising fluid replenishment Summary The purpose of these experiments was to examine the influence of various fluid replacement drinks on exercise-induced disturbances in homeostasis during heavy exercise . Nine trained cyclists performed constant load exercise on a cycle ergometer to fatigue on three occasions with 1-week separating experiments . The work rate was set initially at ∼ 85 % of $ $ \dot V_{o_{2{\text { } } max } } $ $ ( range 82–88 % ) with fatigue being defined as a 10 % decline in power output below the initial value . During each experiment subjects consumed one of the following three beverages prior to and every 15 min during exercise : ( 1 ) non-electrolyte placebo ( NEP ; 31 mosmol · kg−1 ) ; ( 2 ) glucose polymer drink containing electrolytes ( GP ; 7 % CHO , 231 mosmol · kg−1 ) , and ( 3 ) electrolyte placebo drink without carbohydrate ( EP ; 48 mosmol · kg−1 ) . Both the GP and EP beverage contained sodium citrate/citric acid ( C ) as a flavoring agent while C was not contained in the NEP drink . Although seven of nine subjects worked longer during the GP and EP treatment when compared with the NEP trial , the difference was not significant ( P>0.05 ) . No differences ( P>0.05 ) existed between the GP and EP treatments in performance time . Exercise changes in rectal temperature , heart rate , Δ % plasma volume and plasma concentrations of total protein , free fatty acids , glucose , lactate , potassium , chloride , calcium , and sodium did not differ ( P>0.05 ) between trials . In contrast , blood hydrogen ion concentration [ H+ ] was significantly lower ( P<0.05 ) at 30 min of exercise during the GP and EP treatment when compared with the NEP run . These data provide evidence that electrolyte drinks do not minimize exercise-induced disturbances in blood-electrolyte concentrations during heavy execrcise when compared with nonelectrolyte drinks ; however , these results suggest that fluid replacement beverages containing buffers ( i.e. C ) and /or electrolytes may minimize blood alterations in [ H+ ] during intense exercise . Additional research is required to determine if the buffering influence of these beverages has an ergogenic benefit during heavy exercise In an effort to determine the effects of carbohydrate ( CHO ) feedings immediately before exercise in both the fasted and fed state , 10 well-trained male cyclists [ maximum O2 consumption ( VO2 max ) , 4.35 + /- 0.11 l/min ) ] performed 45 min of cycling at 77 % VO2 max followed by a 15-min performance ride on an isokinetic cycle ergometer . After a 12-h fast , subjects ingested 45 g of liquid carbohydrate ( LCHO ) , solid carbohydrate confectionery bar ( SCHO ) , or placebo ( P ) 5 min before exercise . An additional trial was performed in which a high-CHO meal ( 200 g ) taken 4 h before exercise was combined with a confectionery bar feeding ( M + SCHO ) immediately before the activity . At 10 min of exercise , serum glucose values were elevated by 18 and 24 % during SCHO and LCHO , respectively , compared with P. At 0 and 45 min no significant differences were observed in muscle glycogen concentration or total use between the four trials . Total work produced during the final 15 min of exercise was significantly greater ( P less than 0.05 ) during M + SCHO ( 194,735 + /- 9,448 N X m ) , compared with all other trials and significantly greater ( P less than 0.05 ) during LCHO and SCHO ( 175,204 + /- 11,780 and 176,013 + /- 10,465 N X m , respectively ) than trial P ( 159,143 + /- 11,407 N X m ) . These results suggest that , under conditions when CHO stores are less than optimal , exercise performance is enhanced with the ingestion of 45 g of CHO 5 min before 1 h of intense cycling . ( ABSTRACT TRUNCATED AT 250 WORDS It is presently unclear whether the reported ergogenic effect of a carbohydrate ( CHO ) mouth rinse on cycling time-trial performance is affected by the acute nutritional status of an individual . Hence , the aim of this study was to investigate the effect of a CHO mouth rinse on a 60-min simulated cycling time-trial performance commenced in a fed or fasted state . Twelve competitive male cyclists each completed 4 experimental trials using a double-blinded Latin square design . Two trials were commenced 2 h after a meal that contained 2.5 g·kg(-1 ) body mass of CHO ( FED ) and 2 after an overnight fast ( FST ) . Prior to and after every 12.5 % of total time during a performance ride , either a 10 % maltodextrin ( CHO ) or a taste-matched placebo ( PLB ) solution was mouth rinsed for 10 s then immediately expectorated . There were significant main effects for both pre-ride nutritional status ( FED vs. FST ; p < 0.01 ) and CHO mouth rinse ( CHO vs. PLB ; p < 0.01 ) on power output with an interaction evident between the interventions ( p < 0.05 ) . The CHO mouth rinse improved mean power to a greater extent after an overnight fast ( 282 vs. 273 W , 3.4 % ; p < 0.01 ) compared with a fed state ( 286 vs. 281 W , 1.8 % ; p < 0.05 ) . We concluded that a CHO mouth rinse improved performance to a greater extent in a fasted compared with a fed state ; however , optimal performance was achieved in a fed state with the addition of a CHO mouth rinse Summary The availability of carbohydrate ( CHO ) as a substrate for the exercising muscles is known to be a limiting factor in the performance of prolonged cycle exercise , and provision of exogenous CHO in the form of glucose can increase endurance capacity . The present study examined the effects of ingestion of fluids and of CHO in different forms on exercise performance . Six male volunteers exercised to exhaustion on a cycle ergometer at a workload which required approximately 70 % of $ $ \dot V_{O_2 \max } $ $ . After one preliminary trial , subjects performed this exercise test on six occasions , one week apart . Immediately before exercise , and at 10-min intervals throughout , subjects ingested 100 ml of one of the following : control ( no drink ) , water , glucose syrup , fructose syrup , glucose-fructose syrup or a dilute glucose-electrolyte solution . Each of the syrup solutions contained approximately 36 g CHO per 100 ml ; the isotonic glucose-electrolyte solution contained 4 g glucose per 100 ml . A r and omised Latin square order of administration of trials was employed . Expired air sample s for determination of $ $ \dot V_{O_2 } $ $ , respiratory exchange ratio and rate of CHO oxidation were collected at 15-min intervals . Venous blood sample s were obtained before and after exercise . Subjects drinking the isotonic glucose-electrolyte solution exercised longer ( 90.8 ( 12.4 ) min , mean ( SEM ) ) than on the control test ( 70.2 ( 8.3 ) min ; p<0.05 ) . Endurance capacity was not affected by any of the other drinks . Blood glucose concentration at exhaustion was higher when concentrated sugar solutions were given , but no instance of hyperglycaemia or hypoglycaemia was observed in any trial . Neither the rate of CHO oxidation nor the total amount of CHO oxidised was influenced by the ingestion of large quantities of glucose or fructose The effects of a commercial sports drink on performance in high-intensity cycling was investigated . Nine well-trained subjects were asked to complete a set amount of work as fast as possible ( time trial ) following 24 h of dietary ( subjects were provided with food , energy 57.4+/-2.4 kcal/kg and carbohydrate 9.1+/-0.4 g/kg ) and exercise control . During exercise , subjects were provided with 14 mL/kg of either 6 % carbohydrate-electrolyte ( CHO-E ) solution or carbohydrate-free placebo ( P ) . Results showed that subjects ' performances did not greatly improve ( time , 62:34+/-6:44 min : sec ( CHO-E ) vs. 62:40+/-5:35 min : sec ( P ) ; average power output , 283.0+/-25.0 W ( CHO-E ) vs. 282.9+/-29.3 W ( P ) , P > 0.05 ) while consuming the sports drink . It was concluded that CHO-E consumption throughout a 1-h time trial , following a pre-exercise dietary regimen design ed to optimize glucose availability , did not improve time or power output to a greater degree than P in well-trained cyclists Solutions containing multiple carbohydrates utilizing different intestinal transporters ( glucose and fructose ) show enhanced absorption , oxidation , and performance compared with single-carbohydrate solutions , but the impact of the ratio of these carbohydrates on outcomes is unknown . In a r and omized double-blind crossover , 10 cyclists rode 150 min at 50 % peak power , then performed an incremental test to exhaustion , while ingesting artificially sweetened water or one of three carbohydrate-salt solutions comprising fructose and maltodextrin in the respective following concentrations : 4.5 and 9 % ( 0.5-Ratio ) , 6 and 7.5 % ( 0.8-Ratio ) , and Output:	While not mutually exclusive , the primary mechanism(s ) for performance enhancement likely differs depending on the duration of the exercise . In short duration exercise situations ( ∼1 h ) , oral receptor exposure to CHO , via either mouthwash or oral consumption ( with enough oral contact time ) , which then stimulates the pleasure and reward centers of the brain , provide a central nervous system-based mechanism for enhanced performance . Thus , the type and ( or ) amount of CHO and its ability to be absorbed and oxidized appear completely irrelevant to enhancing performance in short duration exercise situations . For longer duration exercise ( > 2 h ) , where muscle glycogen stores are stressed , the primary mechanism by which carbohydrate supplementation enhances performance is via high rates of CHO delivery ( > 90 g/h ) , result ing in high rates of CHO oxidation .
MS2795	*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: Kidney transplant recipients receiving calcineurin inhibitor-based immunosuppression incur increased long-term risks of cancer and kidney fibrosis . Switch to mammalian target of rapamycin ( mTOR ) inhibitors may reduce these risks . Steroid or Cyclosporin Removal After Transplant using Everolimus ( SOCRATES ) , a 36-month , prospect i ve , multinational , open-label , r and omized controlled trial for de novo kidney transplant recipients , assessed whether everolimus switch could enable elimination of mycophenolate plus either steroids or CNI without compromising efficacy . Patients received cyclosporin , mycophenolate and steroids for the first 14 days then everolimus with mycophenolate and CNIwithdrawal ( CNI-WD ) ; everolimus with mycophenolate and steroid withdrawal ( steroid-WD ) ; or cyclosporin , mycophenolate and steroids ( control ) . 126 patients were r and omized . The steroid WD arm was terminated prematurely because of excess discontinuations . Mean eGFR at month 12 for CNI-WD versus control was 65.1 ml/min/1.73 m2 vs. 67.1 ml/min/1.73 m2 by ITT , which met predefined noninferiority criteria ( P = 0.026 ) . The CNI-WD group experienced a higher rate of BPAR(31 % vs. control 13 % , P = 0.048 ) and showed a trend towards higher composite treatment failure ( BPAR , graft loss , death , loss to follow-up ) . The 12 month results from SOCRATES show noninferiority in eGFR , but a significant excess of acute rejection when everolimus was commenced at week 2 to enable a progressive withdrawal of mycophenolate and cyclosporin in kidney transplant recipients The glomerular filtration rate ( GFR ) is traditionally considered the best overall index of renal function in health and disease ( 1 ) . Because GFR is difficult to measure in clinical practice , most clinicians estimate the GFR from the serum creatinine concentration . However , the accuracy of this estimate is limited because the serum creatinine concentration is affected by factors other than creatinine filtration ( 2 , 3 ) . To circumvent these limitations , several formulas have been developed to estimate creatinine clearance from serum creatinine concentration , age , sex , and body size ( 4 - 12 ) . Despite more recent studies that have related serum creatinine concentration to GFR ( 13 - 24 ) , no formula is more widely used to predict creatinine clearance than that proposed by Cockcroft and Gault ( 4 ) . This formula is used to detect the onset of renal insufficiency , to adjust the dose of drugs excreted by the kidney , and to evaluate the effectiveness of therapy for progressive renal disease . More recently , it has been used to document eligibility for reimbursement from the Medicare End Stage Renal Disease Program ( 25 ) and for accrual of points for patients on the waiting list for cadaveric renal transplantation ( 26 ) . Major clinical decisions in general medicine , geriatrics , and oncology ( as well as nephrology ) are made by using the Cockcroft-Gault formula and other formulas to predict the level of renal function . Therefore , these formulas must predict GFR as accurately as possible . The Modification of Diet in Renal Disease ( MDRD ) Study , a multicenter , controlled trial , evaluated the effect of dietary protein restriction and strict blood pressure control on the progression of renal disease ( 27 - 30 ) . During the baseline period , GFR , serum creatinine , and several variables that affect the relation between them were measured in patients with chronic renal disease . The purpose of our study was to develop an equation from MDRD Study data that could improve the prediction of GFR from serum creatinine concentration . Methods Baseline Cohort and Measurement Methods in the Modification of Diet in Renal Disease Study The overall study design and methods of recruitment for the MDRD Study have been described elsewhere ( 31 , 32 ) . A total of 1785 patients entered the baseline period . Of these patients , 1628 ( 91 % ) also underwent measurement of GFR and the other variables described below ; these patients constitute the study group for these analyses . Glomerular filtration rate was measured as the renal clearance of 125I-iothalamate ( 33 , 34 ) . Creatinine clearance was computed from creatinine excretion in a 24-hour urine collection and a single measurement of serum creatinine . Serum and urine creatinine were measured by using a kinetic alkaline picrate assay with a normal range in serum of 62 to 124 mol/L ( 0.7 to 1.4 mg/dL ) ( 35 ) . Glomerular filtration rate and creatinine clearance were expressed per 1.73 m2 of body surface area by multiplying measured values by 1.73/body surface area ( 36 ) . The serum and urine specimens were also used for other measurements , including serum albumin ( bromcresol green method [ 35 ] ) , serum urea nitrogen ( urease method [ 35 ] ) , and urine urea nitrogen ( urease method [ 35 ] ) . Protein intake ( g/d ) was estimated as 6.25 [ UUN ( g/d ) + 0.031 ( g/kg per day ) SBW ( kg ) ] , where UUN is urine urea nitrogen , SBW is st and ard body weight , and 0.031 g/kg per day is a constant reflecting the rate of excretion of nitrogen in compounds other than urine urea ( 37 , 38 ) . The diagnosis of diabetes and the cause of renal disease were assigned on the basis of chart review at the clinical center ( 39 ) . Statistical Analysis Descriptive Statistics The relation of renal function measurements to other baseline characteristics was assessed by using contingency tables , t-tests , analysis of variance , and linear regression , as appropriate . Nonparametric tests ( Wilcoxon rank-sum tests and Kruskal-Wallis tests ) gave consistent results . A P value less than 0.01 was considered statistically significant . Multivariable Analysis of Glomerular Filtration Rate We used stepwise multiple regression to determine a set of variables that jointly predicted GFR . The stepwise regression models were developed by using a training sample consisting of a r and om sample of 1070 of the 1628 patients . We found that the variability of the difference between the observed and predicted GFR values was greater for higher GFR values . This increase was eliminated by performing multiple regressions on log-transformed data . To facilitate clinical interpretation , the results were re-expressed in terms of the original units . Consequently , the prediction equation is a multiplicative model ; regression coefficients refer to the change in geometric mean GFR associated with unit changes in the independent variable . Predicted GFR is expressed in mL/min per 1.73 m2 . The following variables were considered for possible inclusion in the regression model : weight , height , sex , ethnicity , age , diagnosis of diabetes , serum creatinine concentration , serum urea nitrogen level , serum albumin level , serum phosphorus level , serum calcium level , mean arterial pressure , urine creatinine level , urine urea nitrogen level , urine protein level , and urine phosphorus level . The cause of renal disease was not included because in clinical practice , the cause may be unknown or clinicians may not use the same classification method as the investigators in the MDRD Study . A P value less than 0.001 was used as the criterion for entry of a variable into the model . Because of the difficulty in collecting complete 24-hour urine sample s in clinical practice , an additional stepwise regression was performed to develop a prediction model that did not include urine biochemistry variables . Finally , because of the interest in developing a prediction equation to assess eligibility for Medicare reimbursement and listing for cadaveric renal transplantation , we repeated the analysis restricting the population to the subgroup of patients with higher serum creatinine concentrations ( > 221 mol/L [ 2.5 mg/dL ] ; n=509 in the training sample ) . Methods for Comparing Equations To Predict Glomerular Filtration Rate We first developed coefficients for each prediction equation ( including the selection of the predictor variables for the stepwise regressions ) using the data from the training sample to predict log GFR . Each prediction equation also included a multiplicative constant to account for any consistent bias in the application of that equation in the MDRD Study Group . This was particularly important for equations that are intended to estimate creatinine clearance , which is known to be higher than GFR . The regression coefficients determined in the training sample were then applied to obtain predicted GFRs in a separate validation sample consisting of the remaining 558 patients ( 172 patients with serum creatinine concentration>221 mol/L [ 2.5 mg/dL ] ) . These predicted GFR values were compared with the actual GFRs in the validation sample to evaluate the performance of each prediction equation . In this way , separate data sets were used to construct the equations and assess their accuracy after removal of systematic bias . For each equation , we computed overall R 2 ( percentage of variability in log GFR explained by the regression model ) and the 50th , 75th , and 90th percentiles of the distribution of the percentage absolute difference between measured and predicted GFRs in the validation sample . The 50th percentiles indicate the typical size of the errors in prediction of GFR , and the 75th and 90th percentiles assess the sizes of the larger errors that occurred for each model . Development of Final Prediction Equations To improve the accuracy of the final MDRD Study prediction equations , the regression coefficients derived from the training sample were up date d on the basis of data from all 1628 patients . As a result , the st and ard errors of the regression coefficients in the final MDRD Study prediction equations are slightly smaller than those derived from the training sample ; thus , the accuracy of the final prediction equations may be slightly better ( by about 0.1 % to 0.2 % ) than their accuracy as assessed in the validation sample . Results Demographic and Clinical Characteristics The mean age ( SD ) of the cohort was 50.6 12.7 years . Sixty percent of patients were male , 88 % were white , and 6 % were diabetic . Causes of renal disease were glomerular disease ( 32 % ) , polycystic kidney disease ( 22 % ) , tubulointerstitial disease ( 7 % ) , and other or unknown renal diseases ( 40 % ) . Mean protein intake was 0.99 0.24 g/kg of body weight per day and mean arterial pressure was 99.4 12.2 mm Hg . Mean weight was 79.6 16.8 kg , body surface area was 1.91 0.23 m2 , serum urea nitrogen concentration was 11.4 5.7 mmol/L [ 32 16 mg/dL ] , and serum albumin concentration was 40.0 4.0 g/L [ 4.0 0.4 g/dL ] , respectively . Glomerular Filtration Rate , Creatinine Clearance , and Serum Creatinine Concentration Renal function measurements for the study group and for various subgroups are shown in Table 1 . Mean GFR for the population was 0.38 mL s 2 m 2 ( 39.8 mL/min per 1.73 m2 ) , with lower values in patients with lower protein intake , white patients compared with black patients , and older patients ( 55 years ) compared with younger patients ( P<0.01 ) . The mean value of creatinine clearance was 0.81 mL s 2 m 2 ( 48.6 mL/min per 1.73 m2 ) and was lower in older patients and patients with lower protein intake ( P 0.01 ) . The mean serum creatinine concentration was 203 mol/L ( 2.3 mg/dL ) and was higher in men , patients with lower protein intake , and patients with higher mean arterial pressure ( P 0.01 ) . Figure 1 shows the well-known reciprocal relation of serum creatinine concentration to GFR for subgroups based on sex and ethnicity . At any given GFR , the serum creatinine concentration is significantly higher in men than in women and in black persons than in white persons ( P<0.001 ) . Table 1 . Association of Renal BACKGROUND Non-nephrotoxic immunosuppressive strategies that allow reduction of calcineurin-inhibitor exposure without compromising safety or efficacy remain a goal in kidney transplantation . Immunosuppression based on the mammalian-target-of-rapamycin inhibitor everolimus was assessed as a strategy for elimination of calcineurin-inhibitor exposure and optimisation of renal-graft function while maintaining efficacy . METHODS In the ZEUS multicentre , open-label study , 503 patients ( aged 18 - 65 years ) who had received de-novo kidney transplants were enrolled . After initial treatment with ciclosporin , based on trough concentrations , and enteric-coated mycophenolate sodium ( 1440 mg/day , orally ) , corticosteroids ( ≥5 mg/day prednisolone or equivalent , orally ) , and basiliximab induction ( 20 mg , intravenously , on day 0 [ 2 h before transplantation ] , and on day 4 ) , 300 ( 60 % ) patients were r and omly assigned at 4·5 months in a 1:1 ratio to undergo calcineurin-inhibitor elimination ( everolimus-based regimen that was based on trough concentrations [ 6 - 10 ng/mL ] and enteric-coated mycophenolate sodium [ 1440 mg/day ] with corticosteroids ) , or continue st and Output:	Discontinuation secondary to adverse events was more common in patients on mTORi , whereas the incidence of skin cancers and cytomegalovirus infection was lower in patients on mTORi .
MS2796	*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 explores the usefulness of relaxation and gradual medication withdrawal in weaning insomniacs from sleep ( hypnotic ) medication . We recruited 40 volunteers from the community who had insomnia , half of whom were chronic users of hypnotics while the other half were nonmedicated . Half of all participants ( 10 medicated and 10 nonmedicated ) received progressive relaxation . All medicated participants received a st and ard gradual drug withdrawal program . Medicated participants reduced sleep medication consumption by nearly 80 % . Participants who received relaxation obtained additional benefits in sleep efficiency , rated quality of sleep , and reduced withdrawal symptoms . Medicated and nonmedicated participants attained comparable , improved sleep by posttreatment and follow-up . Hypnotic withdrawalwas accompanied by serious worsening of insomnia , but this dissipated by the end of the withdrawal period . The psychological treatment of hypnotic-dependent insomnia has high potential for making an important clinical contribution Forty-five adults with primary insomnia received cognitive-behavioral therapy ( CBT ) implemented in a group therapy format , in individual face-to-face therapy or through brief individual telephone consultations . The results indicate that CBT was effective in improving sleep parameters with all 3 methods of treatment implementation , and there was no significant difference across methods of implementation . All 3 treatment modalities produced improvements in sleep that were maintained for 6 months after treatment completion . These results suggest that group therapy and telephone consultations represent cost-effective alternatives to individual therapy for the management of insomnia Patients with primary insomnia overestimate their sleep onset latency ( SOL ) and underestimate their total sleep time ( TST ) . The present study aim ed to test the utility of a novel behavioural experiment design ed to correct distorted perception of sleep among patients diagnosed with primary insomnia . Individuals with primary insomnia were asked to wear an actigraph and keep a sleep diary for three nights . On the following day , half were shown the discrepancy between the data recorded on the actigraph and their sleep diary ( Shown-Discrepancy Group ) , the other half were not shown the discrepancy ( No-Demonstration Group ) . Participants were then asked to wear the actigraph and keep a sleep diary for three further nights . Following the behavioural experiment , the Shown-Discrepancy Group estimated their SOL more accurately and reported less anxiety and preoccupation about sleep compared to the No-Demonstration Group . The theoretical and clinical implication s of these findings are discussed Objective : To compare treatment outcomes associated with combined pharmacologic and non-pharmacologic treatments for psychophysiological insomnia . Background : Treatments for insomnia have included a variety of pharmacotherapy and cognitive-behavioral interventions , although few studies have investigated the combined efficacy of drug and non-drug therapy . Methods : Forty-one patients with primary insomnia were r and omly assigned to one of three treatment groups : ( i ) estazolam + muscle relaxation , ( ii ) estazolam + guided imagery , and ( iii ) estazolam + sleep education . After 4 weeks of active treatment , subjects were withdrawn from medication and followed for an additional 6 months . Results : Significant improvements were observed in self-report measures of total sleep time , sleep efficiency , and wakefulness after sleep onset in the combined drug and relaxation groups , compared to a significant improvement in total sleep time only in the educational control group . At follow-up , all three groups showed significant improvements across the major sleep measures . Positive changes were also observed in quality of life measures , including mood state and self- ratings of daytime arousal . Conclusions : These findings provide support for the value of combined pharmacotherapy and relaxation training in the treatment of psychophysiological insomnia Previous research suggests that self-defined insomniacs are distinguished from normals by high levels of anxiety and physiological arousal , which might be mitigated by muscle relaxation . This study assessed the relative effects of frontal EMG biofeedback , progressive relaxation , and a placebo set of “ relaxation ” exercises on the sleep of 18 onset insomniacs . Each subject was trained in one of these three methods for six half-hour sessions and slept in the laboratory for two consecutive nights before and after training . The experimental groups demonstrated significant decreases in physiological activity during training while changes in the control group were minimal . Reductions in sleep-onset time were : biofeedback group , 29.66 minutes ; progressive relaxation group , 22.92 minutes ; control group , 2.79 minutes . The experimental groups improved significantly(p<.05 ) more than the control group , but did not differ from each other . No significant relationships between physiological levels and sleep-onset time were found , which suggests that muscle relaxation alone was not responsible for subjects ' improvements . Since 20 minutes of daily practice were required to achieve an approximate 30-minute decrease in sleep-onset time , the practical utility of the methods is question ed Older adults with comorbid insomnia and medical illness have been excluded from behavioral treatment research , but recent evidence suggested that such treatments would be effective with this population . In this study , 38 older adults with comorbid insomnia were r and omized to 1 of 3 conditions : classroom cognitive-behavioral treatment ( CBT ) , home-based audio relaxation treatment ( HART ) , or delayed-treatment control . Compared to the control group , the CBT group had significant changes in 5 of 7 self-report measures of sleep at the 4-month follow-up . The HART group obtained significant outcomes on 3 of 7 measures . Wrist actigraphy measures and secondary - outcome measures did not yield significant findings for either treatment . Clinical ly significant changes at follow-up were obtained for 54 % of patients in CBT , 35 % in HART , and 6 % in the control group when treatment dropouts were included . Although not as effective as in-person CBT , home interventions may have utility as a first-line , low-cost treatment To assess the effect of progressive relaxation training on insomnia in institutionalised chronic alcoholic men , 22 subjects between the ages of 20 and 60 years , were r and omly allocated to treatment and control groups . The treatment group received 10 sessions of progressive relaxation training over a 2-wk . period after which both groups completed a postexperimental question naire . Analysis showed a significant improvement in the sleeping patterns of the treated group , but no changes in the sleeping patterns of the control group . In addition , a distribution-free two- sample permutation test to compare mean differences of the groups confirmed that a significantly greater change occurred in the quality of the sleeping patterns of the treated group This investigation compared progressive muscle relaxation plus cognitive distraction ( PMR/CD ) , hypothesized to better improve sleep onset , versus sleep restriction and stimulus control ( SR/SC ) , hypothesized to better improve sleep maintenance , versus a flurazepam ( Dalmane ) positive contrast condition ( MED ) and a sleep hygiene education minimal treatment control condition ( SHE ) . Participants with chronic insomnia ( N = 53 ) , completed 2 baseline weeks of sleep diaries , and were r and omly assigned to a treatment group for 2 more weeks . In the second phase , PMR/CD participants were assigned to 2 weeks of PMR/CD + SR/SC + SHE while SHE participants continued SHE . Results indicated that PMR/CD had greater effect upon sleep onset than SR/SC and SHE , SR/SC had greater effect on sleep maintenance than PMR/CD , and MED was better than the other treatments . In the second phase , the treatment package produced modest additional improvements and SHE performed superior to expectations OBJECTIVE The question addressed here is : Can a discrete sleep disordered breathing ( SDB ) play a role in the insomnia complaint of postmenopausal chronic insomniacs ? To respond to the query , two groups of individuals derived from a cohort of postmenopausal chronic insomniacs recruited mostly from the community were enlisted in a treatment protocol . These subjects were all individuals identified with normal breathing ( n=68 ) and all those recognized with Upper Airway Resistance Syndrome ( UARS ) ( n=62 ) pooled from a cohort of 349 postmenopausal insomniacs . TREATMENT PROTOCOL The 62 UARS were allocated to either treatment of chronic insomnia by behavioral approaches or treatment of SDB . Based on ENT evaluation , health professionals in charge of patients selected either treatment with nasal CPAP or treatment of nasal turbinates . A stratification correction was performed to obtain a near equal number of both treatment modalities in each of the two subgroups . The 68 individuals with normal breathing were r and omly allocated to immediate behavioral treatment of insomnia or delay treatment of insomnia . The delay treatment received a list of 10 sleep hygiene recommendations by mail . METHODOLOGY Question naires , visual analog scales ( VAS ) , Epworth Sleepiness Scale ( ESS ) , clinical interviews , clinical evaluation with oto-laryngologic clinical assessment of a presence/absence of narrow upper airway and location of narrowing . Actigraphy and polysomnography ( PSG ) with pressure transducer/ and nasal cannula system and esophageal manometry . DATA ANALYSES All recording data were scored blind to patient 's condition . RESULTS Two subjects in the SBD-CPAP treated group ( Group B ) and two subjects in the delayed treatment group ( Group D ) dropped out . Total sleep time was improved compared to baseline in all groups , including the delayed treatment group . One group was significantly better ( ANOVA , P=.05 ) with a more important delta score compared to baseline , and this was the behaviorally treated non-SDB . Sleep latency was significantly decreased in the behaviorally treated group ( with or without SBD ) , P=.05 , compared to SBD-treated and delayed treatment groups . Sleep latency was , however , improved in all groups . VAS for " quality of sleep " was higher at 6 months in all the groups when compared to " baseline " values . VAS for " daytime fatigue " showed significant differences among the four groups ( ANOVA , P=.01 ) ; the overall score at the end of treatment was significantly better in the SDB-treated group than the other three groups . SBD was treated either by radio frequency on nasal turbinate or by nasal CPAP . CPAP-treated patients had a lower VAS score than nasal turbinate treatment , but the difference was only a trend . The delta improvement ( 6-month baseline condition ) in " daytime fatigue " of each subgroup was calculated and compared within and between groups . Despite the small number of subjects , the turbinate-treated subgroup was significantly different from Groups B , C and D ( ANOVA , P=.05 ) . When a similar comparison was made with the nasal CPAP group , there was only a nonsignificant trend when compared to Groups B , C and D. CONCLUSION Abnormal breathing during sleep significantly enhanced complaints of daytime fatigue in postmenopausal chronic insomniacs and this complaint improved with SDB treatment . This improvement is significantly better compared to SDB insomniacs treated with a behavioral regimen . Behavioral treatment , however , gave the best response in the non-SDB chronic insomnia group and improved better long sleep latency even in the SDB group . These results suggest the need to find an appropriate treatment for SBD even if mild and to recognize the role of SDB in relation to symptoms seen with chronic insomnia OBJECTIVE To evaluate the clinical and cost impact of providing cognitive behaviour therapy ( CBT ) for insomnia ( comprising sleep hygiene , stimulus control , relaxation and cognitive therapy components ) to long-term hypnotic drug users in general practice . DESIGN A pragmatic r and omised controlled trial with two treatment arms ( a CBT treated ' sleep clinic ' group , and a ' no additional treatment ' control group ) , with post-treatment assessment s commencing at 3 and 6 months . SETTING Twenty-three general practice s in Sheffield , UK . PARTICIPANTS Two hundred and nine serially referred patients aged 31 - 92 years with chronic sleep problems who had been using hypnotic drugs for at least 1 month ( mean duration = 13.4 years ) . RESULTS At 3- and 6-month follow-ups patients treated with CBT reported significant reductions in sleep latency , significant improvements in sleep efficiency , and significant reductions in the frequency of hypnotic drug use ( all P<0.01 ) . Among CBT treated patients SF-36 scores showed significant improvements in vitality at 3 months ( P<0.01 ) . Older age presented no barrier to successful treatment outcomes . The total cost of service provision was 154.40 per patient , with a mean incremental cost per quality -adjusted life-year of 3416 ( at 6 months ) . However , there was evidence of longer term cost offsets owing to reductions in sleeping tablet use and reduced utilisation of primary care services . CONCLUSIONS In routine general practice setting s , psychological treatments for insomnia can improve sleep quality and reduce hypnotic consumption at a favourable cost among long-term hypnotic users with chronic sleep difficulties Psychological treatment of insomnia has focused on primary insomnia ( i.e. , having a psychological origin ) . Secondary insomnia , sleep disturbance caused by a psychiatric or medical disorder , although it is more common than primary insomnia , has received very little attention as a result of the belief that it would be refractory to treatment . The present study r and omly assigned older adults with secondary insomnia to a treatment group , 4 sessions composed of relaxation and stimulus control , or a no-treatment control group . Self-report assessment s conducted at pretreatment , posttreatment , and a 3-month follow-up revealed that treated participants showed significantly greater improvement on wake time during the night , sleep efficiency percentage , and sleep quality rating . The authors hypothesize that treatment success was probably due in part to difficulty in diagnostic discrimination between primary and secondary insomnia There is substantial experimental evidence that behavioral treatment of insomnia produces significant clinical improvement and that treatment gains tend to be maintained over time . Less clear is whether behavioral treatment is effective as it is plied in clinical setting s. In this clinical case series study , we evaluated 47 patients with primary insomnia . It was found that patients were , on average , 43 % improved . This average Output:	RESULTS Psychological and behavioral therapies produced reliable changes in several sleep parameters of individuals with either primary insomnia or insomnia associated with medical and psychiatric disorders . DISCUSSION These up date d findings provide additional evidence in support of the original review 's conclusions as to the efficacy and generalizability of psychological and behavioral therapies for persistent insomnia .
MS2797	*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 traditional and online teaching methods for educating anesthesiology residents in the principles and practice of difficult airway management . Design Prospect i ve , r and omized , controlled trial . Setting University hospital . Participants Two r and omly selected groups , each containing 28 physicians enrolled from among residents in Anesthesiology and Intensive Care Medicine in Italy . Interventions Residents in Group 1 took a traditional 5-h course on the principles and practice of airway management , which included lectures , slide projection , and dummy demonstrations . The same material was presented to Group 2 in an exclusively online format , which could be individually accessed for a period of 36 h. In the online course , student-instructor interaction was provided through threaded discussion forums during three 30-min real-time question - and -answer sessions . Measurements and results Differences in baseline and post-course scores on written tests and practical skills tests were measured . Knowledge gains in Group 2 were slightly , but not significantly , greater compared with Group 1 both in written ( P=0.228 ) and practical skills ( P=0.376 ) tests . Semi-quantitative ratings of learner satisfaction were significantly higher in the online group ( P=0.014 ) . Almost all online students ( 93 % ) were logged in for at least 45 of the 90 min of real-time question - and -answer sessions . The four instructors spent an average of 144±10 min preparing answers and interacting with online students . Conclusions Online teaching formats may be a valid alternative for teaching residents the principles and practice of difficult airway management . Interaction with instructors seems to be an important element , but it may require substantial time commitments by instructors AIMS AND OBJECTIVES To detect problems when classifying pressure ulcers and to examine whether an e-learning program is able to increase the classification skills of qualified nurses and nursing students . BACKGROUND Both the distinction between pressure ulcer grade s and the differentiation between moisture lesions is difficult . Misclassification and incorrect identification of the lesions results in inadequate preventive and therapeutic measures . Education and training are important for spreading evidence -based insights about this topic . DESIGN Repeated measure design , consisting of one pretest and three posttests . METHODS The experimental intervention consisted of a one-hour session during which the participants independently went over an e-learning program . The control intervention consisted of a one-hour lecture . Both interventions had the same learning contents . A convenience sample of 212 qualified nurses and 214 final-year nursing students was r and omly assigned to an experimental- and a control group . RESULTS In the pretest , the classification skills were low . After the intervention , these skills improved significantly in both groups . The nursing students achieved better results when using the e-learning program . Among the qualified nurses , there was no difference between the learning methods . Although the classification skills decreased in the posttests , they did not drop under the level of the pretest . CONCLUSION The actual classification system does not provide the necessary information about the severity of a pressure ulcer . The differential diagnosis between a moisture lesion was complicated . The classification skills of the qualified nurses and nursing students increased by both learning methods . Repetition remains , however , necessary . RELEVANCE TO CLINICAL PRACTICE Both instruction methods are adequate to acquire the knowledge about the differences between moisture lesions and pressure ulcers . E-learning allows study ing in one 's own time and place , and could therefore be very suitable for repetition of the training . How to organise this training could be a subject for further research Background Exercise is an effective intervention for the prevention of falls ; however , some forms of exercises have been shown to be more effective than others . There is a need to identify effective and efficient methods for training health professionals in exercise prescription for falls prevention . Objective The objective of our study was to compare two approaches for training clinicians in prescribing exercise to prevent falls . Methods This study was a head-to-head r and omized trial design . Participants were physiotherapists , occupational therapists , nurses , and exercise physiologists working in Victoria , Australia . Participants r and omly assigned to one group received face-to-face traditional education using a 1-day seminar format with additional video and written support material . The other participants received Web-based delivery of the equivalent educational material over a 4-week period with remote tutor facilitation . Outcomes were measured across levels 1 to 3 of Kirkpatrick ’s hierarchy of educational outcomes , including attendance , adherence , satisfaction , knowledge , and self-reported change in practice . Results Of the 166 participants initially recruited , there was gradual attrition from r and omization to participation in the trial ( n = 67 Web-based , n = 68 face-to-face ) , to completion of the educational content ( n = 44 Web-based , n = 50 face-to-face ) , to completion of the posteducation examinations ( n = 43 Web-based , n = 49 face-to-face ) . Participant satisfaction was not significantly different between the intervention groups : mean ( SD ) satisfaction with content and relevance of course material was 25.73 ( 5.14 ) in the Web-based and 26.11 ( 5.41 ) in the face-to-face group ; linear regression P = .75 ; and mean ( SD ) satisfaction with course facilitation and support was 11.61 ( 2.00 ) in the Web-based and 12.08 ( 1.54 ) in the face-to-face group ; linear regression P = .25 . Knowledge test results were comparable between the Web-based and face-to-face groups : median ( interquartile range [ IQR ] ) for the Web-based group was 90.00 ( 70.89–90.67 ) and for the face-to-face group was 80.56 ( 70.67–90.00 ) ; rank sum P = .07 . The median ( IQR ) scores for the exercise assignment were also comparable : Web-based , 78.6 ( 68.5–85.1 ) , and face-to-face , 78.6 ( 70.8–86.9 ) ; rank sum P = .61 . No significant difference was identified in Kirkpatrick ’s hierarchy domain change in practice : mean ( SD ) Web-based , 21.75 ( 4.40 ) , and face-to-face , 21.88 ( 3.24 ) ; linear regression P = .89 . Conclusion Web-based and face-to-face approaches to the delivery of education to clinicians on the subject of exercise prescription for falls prevention produced equivalent results in all of the outcome domains . Practical considerations should arguably drive choice of delivery method , which may favor Web-based provision for its ability to overcome access issues for health professionals in regional and remote setting s. Trial Registration Australian New Zeal and Clinical Trials Registry number : ACTRN12610000135011 ; http://www.anzctr.org.au/ACTRN12610000135011.aspx ( Archived by WebCite at http://www.webcitation.org/63MicDjPV OBJECTIVES : We report the results of a r and omized clinical trial of a 3-hour , web-based , tobacco cessation education program , the Web-Based Respiratory Education About Tobacco and Health ( WeBREATHe ) program , for practicing pediatric respiratory therapists ( RTs ) , registered nurses ( RNs ) , and nurse practitioners ( NPs ) . METHODS : Two hundred fifteen RTs ( n = 40 ) , RNs ( n = 163 ) , and NPs ( n = 12 ) employed at the Children ’s Hospital of Philadelphia and the Children ’s Hospital , University of Colorado at Denver , participated in this study . All study activities were completed online . After consenting , participants were r and omly assigned to either the training ( intervention ) or delayed training ( control ) condition . The training condition consisted of a 3-hour continuing education unit course plus ongoing online re sources . Participants were assessed at baseline , 1 week , and 3 months after enrollment . RESULTS : Participants in the training condition were more likely to increase their tobacco cessation intervention behaviors than their delayed training counterparts ( F[1 , 213 ] = 32.03 , P < .001 ) . Training participants showed significantly greater levels of advise ( F[1 , 213 ] = 7.22 , P < .001 ) ; assess ( F[1 , 213 ] = 19.56 , P < .001 ) ; and particularly assist/arrange ( F[1213 ] = 35.52 , P < .001 ) . In addition , training condition participants rated the program highly on measures of consumer satisfaction . CONCLUSIONS : The WeBREATHe program is the first evidence -based education program in tobacco cessation design ed specifically for pediatric RTs , RNs , and NPs . Engagement in WeBREATHe increased participants ’ tobacco cessation-related behaviors Background The introduction of Web-based education and open universities has seen an increase in access to professional development within the health professional education marketplace . Economic efficiencies of Web-based education and traditional face-to-face educational approaches have not been compared under r and omized controlled trial conditions . Objective To compare costs and effects of Web-based and face-to-face short courses in falls prevention education for health professionals . Methods We design ed two short courses to improve the clinical performance of health professionals in exercise prescription for falls prevention . One was developed for delivery in face-to-face mode and the other for online learning . Data were collected on learning outcomes including participation , satisfaction , knowledge acquisition , and change in practice , and combined with costs , savings , and benefits , to enable a break-even analysis from the perspective of the provider , cost-effectiveness analysis from the perspective of the health service , and cost-benefit analysis from the perspective of the participant . Results Face-to-face and Web-based delivery modalities produced comparable outcomes for participation , satisfaction , knowledge acquisition , and change in practice . Break-even analysis identified the Web-based educational approach to be robustly superior to face-to-face education , requiring a lower number of enrollments for the program to reach its break-even point . Cost-effectiveness analyses from the perspective of the health service and cost-benefit analysis from the perspective of the participant favored face-to-face education , although the outcomes were contingent on the sensitivity analysis applied ( eg , the fee structure used ) . Conclusions The Web-based educational approach was clearly more efficient from the perspective of the education provider . In the presence of relatively equivocal results for comparisons from other stakeholder perspectives , it is likely that providers would prefer to deliver education via a Web-based medium . Trial Registration Australian New Zeal and Clinical Trials Registry ( ACTRN ) : 12610000135011 ; http://www.anzctr.org.au/trial_view.aspx?id=335135 ( Archived by WebCite at http://www.webcitation.org/668POww4L The end of the twentieth century and the beginning of the twenty-first century are marked by technology revolution and strategic changes in organizations . Strategies such as the e-learning , has been used for training human re sources . This study aim ed to compare the knowledge acquired among groups of nurses who used e-learning and those who undergone a traditional classroom training . The true-experimental design was used followed by a quantitative analysis . This study was performed at the Hospital and Maternity São Luiz . The study population was composed by 60 nurses , r and omly assigned to two groups , named A and B. Group A received the traditional classroom training and group B received the computer-assisted training . In the data collection , participants filled in a question naire before and after the training to evaluate their knowledge and to characterize the population . Results showed there was an equal acquisition of knowledge in both groups ; confirming the efficacy of both methods Objective To examine the prevalence of outcome reporting bias — the selection for publication of a subset of the original recorded outcome variables on the basis of the results — and its impact on Cochrane review s. Design A nine point classification system for missing outcome data in r and omised trials was developed and applied to the trials assessed in a large , unselected cohort of Cochrane systematic review s. Research ers who conducted the trials were contacted and the reason sought for the non-reporting of data . A sensitivity analysis was undertaken to assess the impact of outcome reporting bias on review s that included a single meta- analysis of the review primary outcome . Results More than half ( 157/283 ( 55 % ) ) the review s did not include full data for the review primary outcome of interest from all eligible trials . The median amount of review outcome data missing for any reason was 10 % , whereas 50 % or more of the potential data were missing in 70 ( 25 % ) review s. It was clear from the publications for 155 ( 6 % ) of the 2486 assessable trials that the research ers had measured and analysed the review primary outcome but did not report or only partially reported the results . For reports that did not mention the review primary outcome , our classification regarding the presence of outcome reporting bias was shown to have a sensitivity of 88 % ( 95 % CI 65 % to 100 % ) and specificity of 80 % ( 95 % CI 69 % to 90 % ) on the basis of responses from 62 trialists . A third of Cochrane review s ( 96/283 ( 34 % ) ) contained at least one trial with high suspicion of outcome reporting bias for the review primary outcome . In a sensitivity analysis undertaken for 81 review s with a single meta- analysis of the primary outcome of interest , the treatment effect estimate was reduced by 20 % or more in 19 ( 23 % ) . Of the 42 meta-analyses with a statistically significant result only , eight ( 19 % ) became non-significant after adjustment for outcome reporting bias and 11 ( 26 % ) would have overestimated the treatment effect by 20 % or more . Conclusions Outcome reporting bias is an under-recognised problem that affects the conclusions in a substantial proportion of Cochrane review s Output:	When compared to traditional learning , e-learning may make little or no difference in patient outcomes or health professionals ' behaviours , skills or knowledge . Even if e-learning could be more successful than traditional learning in particular medical education setting s , general cl aims of it as inherently more effective than traditional learning may be misleading
MS2798	*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 aim ed at exploring nurses ' views of the characteristics of severely demented patients , the difficulties these characteristics produced and the emotional reactions they evoked during the provision of care . Also , it aim ed at exploring any changes in these aspects during a year of regular systematic clinical supervision combined with the implementation of individualized care at an experimental ward ( EW ) ( n = 19 ) and at a control ward ( CW ) ( n = 19 ) . Data were collected by means of the Strain in Nursing Care scale , assessing the presence of certain characteristics in the patients , and how difficult each characteristic can be to h and le . The Emotional Reactions in Nursing Care scale was also used , assessing 18 pairs of emotions . The analysis showed that agitation , not being responsive and unruly behaviour were the most common features while emptiness and agony turned out to be the most difficult problems to h and le in the provision of care . Feelings of defeat and dissociation were reported to be almost as common as feelings of control and association . The EW nurses saw the patients as significantly more responsive , and victims of nihilation to a lesser degree and also patients ' willfulness and emptiness was significantly easier to h and le during the year of intervention . There were no significant changes on the CW . The mean values improved significantly in several aspects on the EW in comparison to the CW ; patients seen as victims of nihilation , easier to h and le agony , obediency , willfulness , evaluation and improved feelings of devotion and beneficence in the nurses . Thus the intervention seemed to improve the nurse-patient relationship and to decrease the experience of strain in the nurses The purpose of the study was to examine the effectiveness of assertiveness training in improving self-perceived levels of stress and assertiveness among nurses in Taiwan , Republic of China . The two-group experimental design was conducted in a 2,000-bed veteran general hospital . A sample of 60 volunteer Chinese-speaking nurses participated in the study . Subjects were r and omly assigned to one of two treatments : assertiveness training ( AT ) or alternate treatment control ( ATC ) , which served as a control and contained up date d knowledge of new computer technology for in patient setting s. Subjects in each group participated in six 2-hour workshops in the same two-week period . All subjects were pre- , post- , and follow-up posttested for stress and assertiveness with the Perceived Stress Scale ( PSS ) and Rathus Assertiveness Schedule ( RAS ) , respectively . Results revealed the following : ( 1 ) subjects in both groups of pretest were clearly subassertive and under considerable stress ; ( 2 ) by the end of training , the AT group scored significantly higher on the rating of assertiveness than those in the ATC group , and had successfully maintained their improvement by the 4-week follow-up ; and ( 3 ) by the end of training , the AT group reported significantly lower levels of stress than the ATC group as indicated on the PSS , and successfully maintained their improvements at the 4-week follow-up . Overall , the results indicate clear support for the effectiveness of assertiveness training for treating subassertive behaviors and stress in a population of professional nurses in Taiwan The usefulness of psychological training programs ( P.T.P. ) in health care setting s devoted to cancer care is beginning to be recognised but their content , form and effectiveness need further investigation . Seventy-two oncology nurses were r and omly assigned to a 24-h P.T.P. or to a waiting list period . Attitudes were assessed by a semantic differential question naire , occupational stress was assessed by the Nursing Stress Scale and communication skills were assessed by st and ardised videotaped role-playing exercises . These were used to compare trained ( T.S. ) and control subjects ( C.S. ) . The results show a significant training effect on attitudes ( P = 0.05 ) , especially on those related to self concept ( P = 0.004 ) , and on the level of occupational stress related to inadequate preparation ( P = 0.02 ) . Limited changes were found regarding post-training communication skills . T.S. were significantly more in control of the interview than C.S. ( P = 0.02 ) . The results indicate that 24-h P.T.P. assessed here are effective . The data also demonstrate the need to consoli date the skills acquired by regular post-training sessions The aim of this study was to study creativity and innovative climate , tedium and burnout among the nurses on two wards during 1 year of systematic clinic supervision combined with the implementation of individualized care on an experimental ward ( EW ) for severely demented patients , as compared with a similar control ward ( CW ) . EW nurses had systematic clinic supervision and each patient had his/her nursing care carefully planned , documented and evaluated . The intervention was evaluated by means of the Creative Climate Question naire , Burnout Measure and the Maslach Burnout Inventory . Creativity and innovative climate improved significantly among the EW nurses ( n = 19 ) in eight out of 10 factors during the year of intervention while there was no change on the control ward ( n = 20 ) . Tedium and burnout decreased significantly among the EW nurses while no change was seen in this respect among the CW nurses . It seems reasonable to assume that systematic clinical supervision and individualized planned care decreases the negative outcome of stress caused by the psychological burden imposed by nursing care . It also increases nurses ' creativity , which , in turn , may benefit patient care . The findings of this study point to the necessity for a support system that focuses on the work itself , i.e. the nursing care . Individualized planned care and systematic clinical supervision may offer this kind of support This study was set up to test the effectiveness of primary nursing on the burnout level of psychiatric nurses . It was expected that , under certain conditions , such as a primary nursing care delivery with an adequate feedback system , the burnout level would decrease . In a quasi-experimental research design , a cohort of 161 psychiatric nurses was followed for 2.5 years . Results showed that although the burnout level did not change as a result of primary nursing , psychiatric nurses and the practical nurses seemed able to work according to the principles of primary nursing . Strong indications were found that the job turnover decreased as a result of the introduction of primary nursing . Because two main problems were encountered in this study , a high drop-out due to job turnover among nurses and the imitation of the intervention by the control group , several additional analyses were performed The purpose of this study was to test the effectiveness of relaxation training , which was based on the cognitive-behavioral model and specifically focused on helping Chinese registered nurses employed in large teaching hospitals to reduce their work stress in Taiwan , Republic of China . The study design was a pretest-posttest control design with two posttest points . The 137 subjects were selected r and omly from three first-ranked teaching hospitals . Twenty-three subjects in the experimental group and 23 in the control group from each hospital participated in the study . The treatment of the experimental group consisted of two sessions of relaxation training based on Smith 's ( 1988 ) cognitive behavioral model of relaxation at weeks 1 and 2 , with a follow-up session in the fifth week . The control group had the same sequence of sessions with a presentation by the research er on theory analysis in nursing . The mean scores on the Nurse Stress Checklist ( NSC ) and the Chinese General Health Question naire ( CGHQ ) differed significantly between the experimental and control group in posttest 2 at week 5 . These results supported the hypotheses that the relaxation training decreased the Chinese nurses ' self-reported work stress as measured by NSC and increased the Chinese nurses ' self-reported psychophysiologic health as measured by CGHQ . The significant difference on means of the CGHQ in posttest 1 at week 2 showed that the self-reported psychophysiologic health level responded to the relaxation training earlier than to the self-reported work stress level . In the relaxation treatment , duration of practice was an important factor of the effectiveness of the treatment on the dependent variable of NSC . It is suggested that even brief teaching of relaxation techniques may reduce work stress levels and promote a sense of psychophysiologic health in Chinese nurses who are employed in large teaching hospitals in Taiwan Output:	There is more evidence for the effectiveness of programmes based on providing personal support than environmental management to reduce stressors .
MS2799	*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 investigate the potential c and i date microRNA ( miRNA ) biomarkers for the clinical diagnosis , classification , and prognosis of gastric cancer ( GC ) . Methods We use bioinformatics overlapping subclasses analysis to find the tumor grade and lymphatic metastasis-related GC specific miRNAs from the Cancer Genome Atlas ( TCGA ) data base . Then , we further investigated these GC specific miRNAs distributions in different GC clinical features and their correlations overall survival on the basis of GC patients ’ information and their related RNA sequencing profile from TCGA . Finally , we r and omly selected some of key miRNAs use qRT-PCR to confirm the reliability and validity . Results 22 GC specific key miRNAs were identified ( Fold-change > 2 , P < 0.05 ) , 11 of them were discriminatively expressed with tumor size , grade , TNM stage and lymphatic metastasis ( P < 0.05 ) . In addition , nine miRNAs ( miR-196b-5p , miR-135b-5p , miR-183 - 5p , miR-182 - 5p , miR-133a-3p , miR-486 - 5p , miR-144 - 5p , miR-129 - 5p and miR-145 - 5p ) were found to be significantly associated with overall survival ( log-rank P < 0.05 ) . Finally , four key miRNAs ( miR-183 - 5p , miR-486 - 5p , miR-30c-2 - 3p and miR-133a-3p ) were r and omly selected to validation and their expression levels in 53 newly diagnosed GC patients by qRT-PCR . Results showed that the fold-changes between TCGA and qRT-PCR were 100 % in agreement . We also found miR-183 - 5p and miR-486 - 5p were significantly correlated with tumor TNM stage ( P < 0.05 ) , and miR-30c-2 - 3p and miR-133a-3p were associated with tumor differentiation degree and lymph-node metastasis ( P < 0.05 ) . These verified miRNAs clinical ly relevant , and the bioinformatics analysis results were almost the same . Conclusion These key miRNAs may functions as potential c and i date biomarkers for the clinical diagnosis , classification and prognosis for GC Background MicroRNAs are aberrantly expressed and correlate with tumourigenesis and the progression of solid tumours . The miR-200 family determines the epithelial phenotype of cancer cells and regulates invasiveness and migration . Thus , we hypothesised that the quantitative detection of the miR-200 family as epithelial-specific microRNAs in the blood could be a useful clinical biomarker for gastric cancer ( GC ) . Methods We initially vali date d the expression levels of miR-200a , 200b , 200c and 141 in GC cell lines ( n = 2 ) and blood from healthy controls ( n = 19 ) using real-time quantitative reverse transcription PCR ( qRT-PCR ) . The microarray expression profiles of the miR-200 family in 160 paired sample s of non-tumour gastric mucosae and GC were downloaded through ArrayExpress and analysed . MiR-200c was selected for clinical validation . The qRT-PCR prospect i ve assessment of miR-200c was performed using 67 blood sample s ( 52 stage I-IV GC patients and 15 controls ) ; the area under the receiver operating characteristic curve ( AUC-ROC ) was estimated . The Kaplan-Meier and Breslow-Wilcoxon tests were used to assess the correlation of miR-200c with overall and progression-free survival ( OS and PFS ) . Multivariate analyses were performed using the Cox model . Results The miR-200c blood expression levels in GC patients were significantly higher than in normal controls ( p = 0.018 ) . The AUC-ROC was 0.715 ( p = 0.012 ) . The sensitivity , specificity and accuracy rates of 65.4 % , 100 % and 73.1 % , respectively , were observed . The levels of miR-200c in the blood above the cutoff defined by the ROC curve was found in 17.6 % of stage I-II GC patients , 20.6 % of stage III patients and 67.7 % of stage IV patients ( p < 0.001 ) . The miR-200c expression levels were not associated with clinical or pathological characteristics or recent surgical procedures . There was a correlation ( p = 0.016 ) with the number of lymph node metastases and the increased expression levels of miR-200c in blood were significantly associated with a poor OS ( median OS , 9 vs 24 months ; p = 0.016 ) and PFS ( median PFS , 4 vs 11 months ; p = 0.044 ) . Multivariate analyses confirmed that the upregulation of miR-200c in the blood was associated with OS ( HR = 2.24 ; p = 0.028 ) and PFS ( HR = 2.27 ; p = 0.028 ) , independent of clinical covariates . Conclusions These data suggest that increased miR-200c levels are detected in the blood of gastric cancer patients . MiR-200c has the potential to be a predictor of progression and survival The occurrence of lymph node metastases ( LNM ) after endoscopic submucosal dissection ( ESD ) in patients with gastric cancer ( GC ) leads to poor prognosis . However , few biomarkers are available to predict LNM in GC patients . Thus , we measured expression of 6 cancer-related miRNAs using real-time RT-PCR in 102 GC sample s that were r and omized into a training set and a testing set ( each , 51 cases ) . Using logistic regression , we identified 4-miRNA ( miR-27b , miR-128 , miR-100 and miR-214 ) signatures for predicting LNM in GC patients . Patients with high-risk scores for the 4-miRNA signature tended to have higher LNM than those with low-risk scores . Meanwhile , the ROC curve of the 4-miRNA signature was better for predicting LNM in GC patients . In addition , Cox regression analysis indicated that a 2-miRNA signature ( miR-27b and miR-214 ) or a miR-214/N stage signature was predictive of survival for GC patients . This work describes a previously unrecognized 4-miRNA signature involved in LNM and a 2-miRNA signature or miR-214/N stage signature related to GC patients ’ survival Output:	In summary , miR-20b , 21 , 106b , 125a , 137 , 141 , 145 , 146a , 196a , 196b , 206 , 214 , 218 , 451 , 486 - 5p and 506 demonstrate significantly prognostic value . Among them , miR-20b , 125a , 137 , 141 , 146a , 196a , 206 , 218 , 486 - 5p and 506 are strong biomarkers of prognosis in GC

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