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MS21300	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Since the patient 's skin is a major source of pathogens that cause surgical-site infection , optimization of preoperative skin antisepsis may decrease postoperative infections . We hypothesized that preoperative skin cleansing with chlorhexidine-alcohol is more protective against infection than is povidone-iodine . METHODS We r and omly assigned adults undergoing clean-contaminated surgery in six hospitals to preoperative skin preparation with either chlorhexidine-alcohol scrub or povidone-iodine scrub and paint . The primary outcome was any surgical-site infection within 30 days after surgery . Secondary outcomes included individual types of surgical-site infections . RESULTS A total of 849 subjects ( 409 in the chlorhexidine-alcohol group and 440 in the povidone-iodine group ) qualified for the intention-to-treat analysis . The overall rate of surgical-site infection was significantly lower in the chlorhexidine-alcohol group than in the povidone-iodine group ( 9.5 % vs. 16.1 % ; P=0.004 ; relative risk , 0.59 ; 95 % confidence interval , 0.41 to 0.85 ) . Chlorhexidine-alcohol was significantly more protective than povidone-iodine against both superficial incisional infections ( 4.2 % vs. 8.6 % , P=0.008 ) and deep incisional infections ( 1 % vs. 3 % , P=0.05 ) but not against organ-space infections ( 4.4 % vs. 4.5 % ) . Similar results were observed in the per- protocol analysis of the 813 patients who remained in the study during the 30-day follow-up period . Adverse events were similar in the two study groups . CONCLUSIONS Preoperative cleansing of the patient 's skin with chlorhexidine-alcohol is superior to cleansing with povidone-iodine for preventing surgical-site infection after clean-contaminated surgery . ( Clinical Trials.gov number , NCT00290290 . Abstract Povidone-iodine and chlorhexidine surgical scrub and skin preparation solutions were assessed by comparing postoperative wound infection rates in a prospect i ve , r and omized study of 866 patients . The frequency of wound infection overall , as agreed by two observers , was 14·8 per cent in the povidone-iodine group and 9·7 per cent in the chlorhexidine group ( P = 0·03 ) at the time of patients ' discharge from hospital . The difference between the compounds was not significant at a ‘ st and ard ' observation period of three to four days after operation . There were significantly fewer infections with chlorhexidine than with povidone-iodine in operations on the biliary tract and in ‘ clean ' non-abdominal operations , but there were more infections ( not significantly so ) with chlorhexidine than with povidoneiodine in large bowel surgery , other laparotomies and in operations on hernia , genitalia and varicose veins . The differences in bacterial isolates from wounds tended to follow the above patterns . We conclude that , on the evidence of this study , there is no overwhelming case for using one compound rather than the other as an all- purpose preparation and scrub OBJECTIVE We estimated the impact of hip replacement-associated surgical site infection ( SSI ) on morbidity and length of stay . METHODS This was a pairwise matched ( 1 : 1 ) case-control study nested in a cohort . All patients who underwent hip replacement from January 1 , 2000 , to June 30 , 2004 , were prospect ively enrolled for the nested case-control design analysis and were monitored from the time of surgery until hospital discharge , including any patients readmitted because of infection . RESULTS Among the 1,260 hip replacements performed , 28 SSIs were detected , yielding a crude SSI rate of 2.2 % . The median excess length of stay attributable to SSI was 32.5 days ( P<.001 ) , whereas the median prolonged postoperative stay due to SSI was 31 days ( P<.001 ) . Deep-wound SSI was the type that prolonged hospital stay the most ( up to 49 days ) . Of the patients who developed an SSI , 4 required revision surgery , for an SSI-related morbidity rate of 14.3 % . CONCLUSION SSI prolongs hospital stay ; however , although hospital stay is a rough indicator of the cost of this complication , to accurately estimate the costs of SSI , we would need to consider individual costs in a linear regression model adjusted for all possible confounding factors OBJECTIVE To analyze the incidence of surgical site infection when the preoperative skin preparation was performed with 10 % povidone-iodine and 0.5 % chlorhexidine-alcohol . METHODS We conducted a r and omized , longitudinal study based on variables obtained from patients undergoing clean and potentially contaminated operations . Those involved were divided into two groups . In group 1 ( G1 ) we included 102 patients with skin prepared with povidone-iodine , and in group 2 ( G2 ) , 103 , whose skin was prepared with chlorhexidine . In the third , seventh and 30th postoperative days we evaluated the surgical site , search ing for signs of infection . RESULTS Data related to clinical profile , such as diabetes mellitus , smoking , alcoholism , haematological data ( Hb , VG and leukocytes ) , age and gender , and the related variables , such as number of days of preoperative hospitalization , shaving , topography of incision , antibiotic prophylaxis and resident participation in the operation were not predisposing factors for surgical site infection . Two patients in G1 and eight in G2 undergoing clean operations had some type of infection ( p = 0.1789 ) , five in G1 and three in G2 undergoing potentially contaminated operations had some type of infection ( p = 0.7205 ) . CONCLUSION The incidence of surgical site infection in operations classified as clean and as potentially contaminated for which skin preparation was done with 10 % povidone-iodine and 0.5 % chlorhexidine-alcohol was similar Abstract Background / Aims : To compare the prevalence of positive bacterial cultures at the cesarean delivery ( CD ) incision site in patients with pre-operative application of chlorhexidine gluconate ( CG ) versus povidone iodine ( PI ) . Methods : Women undergoing a scheduled CD at ≥36 gestational weeks were r and omly assigned to receive CG or PI . A swab of the incision site was performed at 3 min after disinfectant application and at 18 post-operative hours , and the prevalence of cultures with any detected bacterial growth was compared for the two groups . Results : Of the 60 participants , 33 ( 55.0 % ) were in the PI group . There were no differences detected at 3 min , with 9.1 % positive in the PI group versus 0 % positive in the CG group ( p = 0.2499 ) . However , at 18 h , women in the PI group were seven times more likely than women in the CG group to have a positive culture ( 16/33 [ 48.5 % ] versus 3/27 [ 11.1 % ] , OR = 7.53 [ 95 % CI 1.67–38.83 ] , p = 0.0023 ) . Multivariate logistic regression demonstrated similar results : OR = 7.33 ( 95 % CI 1.77–30.35 ) , p = 0.0060 . Conclusion : The prevalence of positive bacterial cultures obtained at the site of the skin incision 18 h after CD was higher in the PI versus the CG group BACKGROUND Postoperative spinal wound infections are relatively common and are often associated with increased morbidity and poor long-term patient outcomes . The purpose s of this study were to identify the common bacterial flora on the skin overlying the lumbar spine and evaluate the efficacy of readily available skin-preparation solutions in the elimination of bacterial pathogens from the surgical site following skin preparation . METHODS A prospect i ve r and omized study was undertaken to evaluate 100 consecutive patients undergoing elective lumbar spine surgery . At the time of surgery , the patients were r and omized to be treated with one of two widely used , and Food and Drug Administration ( FDA ) -approved , surgical skin-preparation solutions : ChloraPrep ( 2 % chlorhexidine gluconate and 70 % isopropyl alcohol ) or DuraPrep ( 0.7 % available iodine and 74 % isopropyl alcohol ) . Specimens for aerobic and anaerobic cultures were obtained prior to skin preparation ( pre-preparation ) , after skin preparation ( post-preparation ) , and after wound closure ( post-closure ) . A vali date d neutralization solution was used for each culture to ensure that the antimicrobial activity was stopped immediately after the sample was taken . Positive cultures and specific bacterial pathogens were recorded . RESULTS Coagulase-negative Staphylococcus , Propionibacterium acnes , and Corynebacterium were the most commonly isolated organisms prior to skin preparation . The overall rate of positive cultures prior to skin preparation was 82 % . The overall rate of positive cultures after skin preparation was 0 % ( zero of fifty ) in the ChloraPrep group and 6 % ( three of fifty ) in the DuraPrep group ( p = 0.24 , 95 % confidence interval [ CI ] = 0.006 to 0.085 ) . There was an increase in positive cultures after wound closure , but there was no difference between the ChloraPrep group ( 34 % , seventeen of fifty ) and the DuraPrep group ( 32 % , sixteen of fifty ) ( p = 0.22 , 95 % CI = 0.284 to 0.483 ) . Body mass index ( BMI ) , duration of surgery , and estimated blood loss did not a show significant association with post-closure positive culture results . CONCLUSIONS ChloraPrep and DuraPrep are equally effective skin-preparation solutions for eradication of common bacterial pathogens on the skin overlying the lumbar spine OBJECTIVE The purpose of this study was to compare the efficacy of chlorhexidine and povidone iodine for cleansing the operative field for vaginal surgery . STUDY DESIGN This was a r and omized controlled trial that compared 10 % povidone iodine and 4 % chlorhexidine gluconate as surgical scrubs . Our primary end point was the proportion of contaminated specimens ( defined as total bacterial colony counts of > /=5000 colony-forming units ) per group found throughout the surgical procedures . All patients received st and ard infection prophylaxis that included preoperative intravenous antibiotics . Immediately before antibiotic administration and baseline aerobic and anaerobic cultures of the vaginal flora were obtained , which were followed by cultures at 30 minutes after the surgical scrub and hourly thereafter throughout each patient 's surgery . RESULTS A total of 50 patients were enrolled between October 2002 and September 2003 . There were no differences between the povidone iodine ( n = 27 ) and chlorhexidine ( n = 23 ) groups with respect to age , race , exogenous hormone use , body mass index , gravity , parity , preoperative mean colony counts , or operative time . Among the first set of intraoperative specimens ( which were obtained 30 minutes after the surgical scrub ) , 63 % of the cultures ( 17/27 ) from the povidone iodine group and 22 % of the cultures ( 5/23 ) from the chlorhexidine group were classified as contaminated ( P = .003 ; relative risk , 6.12 ; 95 % CI , 1.7 , 21.6 ) . Subsequent cultures failed to demonstrate significant differences . CONCLUSION Chlorhexidine gluconate was more effective than povidone iodine in decreasing the bacterial colony counts that were found in the operative field for vaginal hysterectomy Background Surgical site infections ( SSI ) remain a major clinical problem in terms of morbidity , mortality , and hospital costs . Nearly 60 % of SSI diagnosis occur in the postdischarge period . However , literature provides little information on risk factors associated to in-hospital and postdischarge SSI occurrence . A national prospect i ve multicenter study was conducted with the aim of assessing the incidence of both in-hospital and postdisharge SSI , and the associated risk factors . Methods In 2002 , a one-month , prospect i ve national multicenter surveillance study was conducted in General and Gynecological units of 48 Italian hospitals . Case ascertainment of SSI was carried out using st and ardized surveillance methodology . To assess potential risk factors for SSI we used a conditional logistic regression model . We also reported the odds ratios of in-hospital and postdischarge SSI . Results SSI occurred in 241 ( 5.2 % ) of 4,665 patients , of which 148 ( 61.4 % ) during in-hospital , and 93 ( 38.6 % ) during postdischarge period . Of 93 postdischarge SSI , sixty-two ( 66.7 % ) and 31 ( 33.3 % ) were detected through telephone interview and question naire survey , respectively . Higher SSI incidence rates were observed in colon surgery ( 18 Output:	Conclusions : There is moderate‐ quality evidence supporting the use of chlorhexidine for preoperative skin antisepsis and high‐ quality evidence that the use of chlorhexidine is associated with fewer positive skin cultures .
MS21301	*TASK* the task is to summarize an input biomedical literature in six sentences *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 We conducted an open-label , r and omized trial to determine whether ICRF-187 would reduce doxorubicin-induced cardiotoxicity in pediatric sarcoma patients . METHODS Thirty-eight patients were r and omized to receive doxorubicin-containing chemotherapy ( given as an intravenous bolus ) with or without ICRF-187 . Resting left ventricular ejection fraction ( LVEF ) was monitored serially with multigated radionuclide angiography ( MUGA ) scan . The two groups were compared for incidence and degree of cardiotoxicity , response rates to four cycles of chemotherapy , event-free and overall survival , and incidence and severity of noncardiac toxicities . RESULTS Eighteen ICRF-187-treated and 15 control patients were assessable for cardiac toxicity . ICRF-187-treated patients were less likely to develop sub clinical cardiotoxicity ( 22 % v 67 % , P < .01 ) , had a smaller decline in LVEF per 100 mg/m2 of doxorubicin ( 1.0 v 2.7 percentage points , P = .02 ) , and received a higher median cumulative dose of doxorubicin ( 410 v 310 mg/m2 , P < .05 ) than did control patients . Objective response rates were identical in the two groups , with no significant differences seen in event-free or overall survival . ICRF-187-treated patients had a significantly higher incidence of transient grade 1 serum transaminase elevations and a trend toward increased hematologic toxicity . CONCLUSION ICRF-187 reduces the risk of developing short-term sub clinical cardiotoxicity in pediatric sarcoma patients who receive up to 410 mg/m2 of doxorubicin . Response rates to chemotherapy , event-free and overall survival , and noncardiac toxicities appear to be unaffected by the use of ICRF-187 . Additional clinical trials with larger numbers of patients are needed to determine if the short-term cardioprotection afforded by ICRF-187 will reduce the incidence of late cardiac complications in long-term survivors of childhood cancer Anthracyclines are a group of drugs that are useful in the treatment of Hodgkin 's disease , but have been associated with severe , and in some cases lethal , cardiac toxicity . Apparently , cardiac toxicity is more frequent after 10 years of anthracycline therapy , but no longer studies of cardiac toxicity have been reported . Four hundred and seventy-six patients with Hodgkin 's disease , stages III and IV , were r and omly assigned to receive ABVD ( doxorubicin , bleomycin , vinblastine and dacarbazine ) compared with EBVD ( epirubicin instead of doxorubicin ) and MBVD ( mitoxantrone instead of doxorubicin ) at st and ard doses . The endpoint was the presence of a clinical cardiac event ( CCE ) or abnormalities in equilibrium radionuclide angiocardiography ( ERNA ) and echocardiogram . The patients did not receive radiation therapy and when relapsed they were censored from cardiac toxicity . The median follow-up was 11.5 years ( range 7.5 - 14.8 years ) . CCE was observed in 17 % in the MBVD arm , 9 % in the ABVD arm and 6 % in the EBVD arm ( P < 0.001 ) . Mortality associated with CCE was 12 % with MBVD , 7 % with ABVD and 2 % with EBVD . Abnormalities in ERNA and echocardiogram were observed 6 - 36 months before the presence of a CCE . An excess in the st and ard mortality ratio was observed with the 3 regimens when compared with the general population : 19.4 for EBVD , 46.0 for ABVD and 67.8 for MBVD , which was confirmed with an increase in absolute excess risk/10,000 person-years of 15.6 , 39.0 and 58.7 , respectively . Overall survival was better in patients treated with EBVD because less cardiac events were observed . The use of mitoxantrone was associated with a high rate of relapse and cardiac events . Thus , we would not recommend use of the drug in Hodgkin 's disease . ERNA and echocardiogram are early detection tests for cardiac toxicity and can be employed in surveillance studies BACKGROUND Doxorubicin chemotherapy is very effective in children with acute lymphoblastic leukemia ( ALL ) but also injures myocardial cells . Dexrazoxane , a free-radical scavenger , may protect the heart from doxorubicin-associated damage . METHODS To determine whether dexrazoxane decreases doxorubicin-associated injury of cardiomyocytes , we r and omly assigned 101 children with ALL to receive doxorubicin alone ( 30 mg per square meter of body-surface area every three weeks for 10 doses ) and 105 to receive dexrazoxane ( 300 mg per square meter ) followed immediately by doxorubicin . Serial measurements of serum cardiac troponin T were obtained in 76 of 101 patients in the doxorubicin group and 82 of 105 patients in the group given dexrazoxane and doxorubicin . A total of 2377 serum sample s ( mean , 15.1 sample s per patient ) were obtained before , during , and after treatment with doxorubicin . Troponin T levels were evaluated in a blinded fashion to determine whether they were elevated ( > 0.01 ng per milliliter)--the primary end point -- or extremely elevated ( > 0.025 ng per milliliter ) . RESULTS Elevations of troponin T occurred in 35 percent of the patients ( 55 of 158 ) . Patients treated with doxorubicin alone were more likely than those who received dexrazoxane and doxorubicin to have elevated troponin T levels ( 50 percent vs. 21 percent , P<0.001 ) and extremely elevated troponin T levels ( 32 percent vs. 10 percent , P<0.001 ) . The median follow-up was 2.7 years . The rate of event-free survival at 2.5 years was 83 percent in both groups ( P=0.87 by the log-rank test ) . CONCLUSIONS Dexrazoxane prevents or reduces cardiac injury , as reflected by elevations in troponin T , that is associated with the use of doxorubicin for childhood ALL without compromising the antileukemic efficacy of doxorubicin . Longer follow-up will be necessary to determine the influence of dexrazoxane on echocardiographic findings at four years and on event-free survival Doxorubicin has been used in the the treatment of malignant tumors in children . Its use is limited by cardiotoxic effects beyond a cumulative dose of 450 mg/m2 . To detect cardiotoxicity at an early stage and identify patients at risk for development of cardiotoxicity are matters of concern . Recently , cardiac troponin I ( cTnI ) has been reported to be useful for detecting minor myocardial damage . In the present study , we investigated whether cumulative doxorubicin-related myocardial cell damage can potentially increase cTnI levels above the expected values in 22 patients treated with cumulative doxorubicin doses of 120 to 450 mg/m2 . Impaired cardiac functions were found in three patients by echocardiography , but serum CTnI levels were within the ranges expected in healthy individuals both in patients with cumulative doxorubicin doses > or = 400 mg/m2 and in patients with disturbed cardiac functions . We found no relationship between serum cTnI , cumulative dose of doxorubicin , and echocardiographical findings Two hundred fourteen eligible patients with previously untreated , localized Ewing 's sarcoma of bone were r and omized on IESS-II to receive Adriamycin ( ADR ; doxorubicin ; Adria Laboratories , Columbus , OH ) , cyclophosphamide , vincristine , and dactinomycin by either a high-dose intermittent method ( treatment [ trt ] 1 ) or a moderate-dose continuous method ( trt 2 ) similar to the four-drug arm of IESS-I. Patient characteristics ( sex , primary site , type of surgery ) were stratified at the time of registration ; these and other patient characteristics ( age , time from symptoms to diagnosis , race ) were distributed similarly between treatments . Surgical resection was encouraged , but not m and atory . Local radiation therapy was the same as for IESS-I. The median follow-up time is 5.6 years . The overall outcome was significantly better on trt 1 than on trt 2 . At 5 years , the estimated percentages of patients who were disease-free , relapse-free , and surviving were 68 % , 73 % , and 77 % for trt 1 and 48 % , 56 % , and 63 % for trt 2 ( P = .02 , .03 , and .05 , respectively ) . The major reason for treatment failure for both treatment groups was the development of metastatic disease . The lung was the most common site of metastases followed by bone sites . The combined incidence of severe or worse toxicity ( 67 % ) was comparable between the treatments ; however , severe or worse cardiovascular toxicity was significantly greater on trt 1 . Tne only treatment-associated deaths ( N = 3 ) were on trt 1 and were cardiac-related The objective of this study is to assess the efficacy of ICRF-187 as a protective agent against anthracycline cardiotoxicity . Cardiac function was evaluated by echocardiography before and after each cycle of anthracycline chemotherapy associated with ICRF-187 and compared with that of a second group receiving anthracycline chemotherapy without ICRF-187 . The patients were a group of 15 consecutive children affected with various types of solid tumors who were treated with either doxorubicin-daunomycin or epirubicin ( average doses 340 and 280 mg/m2 , respectively ) , and treatment was associated with ICRF-187 . A second group of 15 consecutive children affected with different malignancies were simultaneously treated with either doxorubicin-daunomycin or epirubicin ( average doses 309 and 270 mg/m2 , respectively ) , but without ICRF-187 association . None of the patients treated with anthracyclines and ICRF-187 association showed abnormalities on echocardiographic examination . In the second group of patients treated with anthracyclines but without ICRF-187 association , we observed a decrease in the left ventricular ejection fraction to < 55 % and a decrease in the left ventricular fractional shortening to < 28 % in two patients ( 13.3 % ) . One of these ( 6.6 % ) showed a dilatative cardiomyopathy . Both groups of patients were treated with low doses of anthracyclines . Although this study was not r and omized , in patients without ICRF-87 cardioprotection , there was a trend for a worse evolution with one case of clinical cardiomyopathy as well as sub clinical cardiac abnormalities Doxorubicin is one of the most effective anticancer drug , but its usefulness is limited by the risk of developing cardiomyopathy , cardiac dysfunction and ventricular arrhythmias . Dexrazoxane is used to protect against doxorubicin cardiotoxicity . It is uncertain whether the dexrazoxane-mediated cardioprotective effect will be reflected in electrophysiological properties of the heart . The aim of the present study was to evaluate the occurrence of frequency-domain signal-averaged electrocardiographic ( SAECG ) abnormalities of the QRS complex and the initial ST segment in patients treated with and without dexrazoxane . Thirty children and young adults 2 months - 15 years after completion of doxorubicin-containing therapy for Hodgkin 's disease were evaluated with SAECG . Patients from group I ( n = 13 ) received combined therapy with doxorubicin and dexrazoxane ( DOX/DZX ) , patients from group II ( n = 17 ) received doxorubicin without dexrazoxane ( DOX ) . Using fast Fourier transformation within the QRS complex and the initial ST segment , area ratio ( AR ) values 40 - 100/0 - 40 Hz were calculated . Significant differences in these frequency parameters in the QRS complex between DOX/DZX group and DOX group ( 19.45+/-12.72 vs 46.18+/-43.06 ; p = 0.03 ) might indicate protective effect of dexrazoxane on electrophysiological myocardial properties Doxorubicin is an anthracycline antibiotic with a broad spectrum of antineoplastic activity . Cardiotoxicity is a serious long-term complication of the drug . Simultaneous administration of carnitine has been proposed to prevent cardiotoxicity . We aim ed to monitor the serum carnitine levels during the treatment of doxorubicin and to determine a relationship between serum carnitine levels and cardiac dysfunction . Fifteen patients were evaluated prospect ively . Measurement of carnitine levels and evaluation of cardiac function were performed prior to treatment , and after cumulative doses of 180 and 300 mg/m2 of doxorubicin . A group of 20 healthy children served as control group to obtain reference values . We found sub clinical abnormalities in cardiac function , while the cum Output:	Two cohort studies considering atrial natriuretic peptide and two considering brain ( B-type ) natriuretic peptide suggested that these chemicals are elevated in some subgroups of children treated with anthracyclines for cancer . This will have an impact on cardiac services and costs .
MS21302	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Perioperative anemia leads to increased morbidity and mortality and potentially inhibits rehabilitation after hip fracture surgery . As such , the optimum transfusion threshold after hip fracture surgery is unknown . PATIENTS AND METHODS A total of 120 elderly , cognitively intact hip fracture patients admitted from their own home were r and omly assigned to receive transfusion at a hemoglobin threshold of 10.0 g per dL ( liberal ) versus 8.0 g per dL ( restrictive ) in the entire perioperative period . Patients were treated according to a well-defined multimodal rehabilitation program . Primary outcome was postoperative functional mobility measured with the cumulated ambulation score ( CAS ) . RESULTS Patients in the liberal group received transfusions more frequently than those in the restrictive group ( 44 patients vs. 22 patients ; p < 0.01 ) and received more transfusions during hospitalization ( median , 2 units [ interquartile range , 1 - 2 ] vs. 1 [ 1 - 2 ] ; p < 0.0001 ) . There were no significant differences in postoperative rehabilitation scores ( CAS : median , 9 [ 9 - 15 ] vs. 9 [ 9 - 13.5 ] ; p = 0.46 ) or in length of stay ( median , 18 days vs. 16 days , respectively ; p = 0.46 ) . There were fewer patients in the liberal transfusion group with cardiovascular complications ( 2 % vs. 10 % ; p = 0.05 ) and a lower mortality ( 0 % vs. 8 % ; p = 0.02 ) . CONCLUSION Although a liberal transfusion trigger did not result in increased ambulation scores , restrictive transfusion thresholds should be treated with caution in elderly high-risk hip fracture patients , until their safety has been proved in larger r and omized studies BACKGROUND AND OBJECTIVES Red cell transfusion is commonly used in orthopaedic surgery . Evidence suggests that a restrictive transfusion strategy may be safe for most patients . However , concern has been raised over the risks of anaemia in those with ischaemic cardiac disease . Perioperative silent myocardial ischaemia ( SMI ) has a relatively high incidence in the elderly population undergoing elective surgery . This study used Holter monitoring to compare the effect of a restrictive and a liberal red cell transfusion strategy on the incidence of SMI in patients without signs or symptoms of ischaemic heart disease who were undergoing lower limb arthroplasty . MATERIAL S AND METHODS We performed a multicentre , controlled trial in which 260 patients undergoing elective hip and knee replacement surgery were enrolled and r and omized to transfusion triggers that were either restrictive ( 8 g/dl ) or liberal ( 10 g/dl ) . Participants were monitored with continuous ambulatory electrocardiogram ( ECG ) ( Holter monitoring ) , preoperatively for 12 h and postoperatively for 72 h. The tapes were analysed for new ischaemia by technicians blinded to treatment . The total ischaemia time in minutes was divided by the recording time in hours and an ischaemic load in min/h was calculated . Haemoglobin levels were measured preoperatively , postoperatively in the recovery room , and on days one , three and five after surgery . RESULTS The mean postoperative haemoglobin concentration was 9.87 g/dl in the restrictive group and 11.09 g/dl in the liberal group . In the restrictive group , 34 % were transfused a total of 89 red cell units , and in the liberal group 43 % were given a total of 119 red cell units . A postoperative episode of silent ischaemia was experienced by 21/109 ( 19 % ) patients in the restrictive group and by 26/109 ( 24 % ) patients in the liberal group [ mean difference -4.6 % ; 95 % confidence interval ( CI ) : -15.5 % to 6 % , P = 0.41 ) . There was no significant difference ( P = 0.53 ) between the overall ischaemic load in the restrictive group ( median 0 min/h , range 0 - 4.18 ) and the liberal group ( median 0 min/h , range 0 - 19.48 ) . In those patients who did experience postoperative SMI , the mean ischaemic load was 0.48 min/h in the restrictive group and 1.51 min/h in the liberal group ( ratio 0.32 , 95 % CI : 0.14 - 0.76 , P = 0.011 ) . The median postoperative length of hospital stay in the restrictive group was 7.3 days [ range 5 - 11 ; interquartile range ( IQR ) 6 - 8 ] compared with 7.5 days ( range 5 - 13 ; IQR 7 - 8 ) in the liberal group . The numbers were not large enough to conclude equivalence . CONCLUSIONS In patients without preoperative evidence of myocardial ischaemia undergoing elective hip and knee replacement surgery , a restrictive transfusion strategy seems unlikely to be associated with an increased incidence of SMI . A proportion of these patients experience moderate SMI , regardless of the transfusion trigger . Use of a restrictive transfusion strategy did not increase length of hospital stay , and use of this strategy would lead to a significant reduction in red cell transfusion in orthopaedic surgery . Our data did not indicate any potential for harm in employing such a strategy in patients with no prior evidence of cardiac ischaemia who were undergoing elective orthopaedic surgery Objective To evaluate the immediate effects of red blood cell transfusion on central venous oxygen saturation and lactate levels in septic shock patients with different transfusion triggers . Methods We included patients with a diagnosis of septic shock within the last 48 hours and hemoglobin levels below 9.0g/dL Patients were r and omized for immediate transfusion with hemoglobin concentrations maintained above 9.0g/dL ( Group Hb9 ) or to withhold transfusion unless hemoglobin felt bellow 7.0g/dL ( Group Hb7 ) . Hemoglobin , lactate , central venous oxygen saturation levels were determined before and one hour after each transfusion . Results We included 46 patients and 74 transfusions . Patients in Group Hb7 had a significant reduction in median lactate from 2.44 ( 2.00 - 3.22 ) mMol/L to 2.21 ( 1.80 - 2.79 ) mMol/L , p = 0.005 , which was not observed in Group Hb9 [ 1.90 ( 1.80 - 2.65 ) mMol/L to 2.00 ( 1.70 - 2.41 ) mMol/L , p = 0.23 ] . Central venous oxygen saturation levels increased in Group Hb7 [ 68.0 ( 64.0 - 72.0)% to 72.0 ( 69.0 - 75.0)% , p < 0.0001 ] but not in Group Hb9 [ 72.0 ( 69.0 - 74.0)% to 72.0 ( 71.0 - 73.0)% , p = 0.98 ] . Patients with elevated lactate or central venous oxygen saturation < 70 % at baseline had a significant increase in these variables , regardless of baseline hemoglobin levels . Patients with normal values did not show a decrease in either group . Conclusion Red blood cell transfusion increased central venous oxygen saturation and decreased lactate levels in patients with hypoperfusion regardless of their baseline hemoglobin levels . Transfusion did not appear to impair these variables in patients without hypoperfusion . Clinical Trials.gov OBJECTIVE In elective orthopaedic hip- and knee replacement surgery patients , we studied the effect of implementation of a uniform transfusion policy on RBC usage . STUDY DESIGN AND METHODS A r and omized , controlled study . A new uniform , restrictive transfusion policy was compared with st and ard care , which varied among the three participating hospitals . Only prestorage leucocyte-depleted RBC(s ) were used . Primary end-point was RBC usage , related to length of hospital stay . Secondary end-points were Hb levels , mobilization delay and postoperative complications . RESULTS Six hundred and three patients were evaluated . Adherence to the protocol was over 95 % . Overall mean RBC usage was 0.78 U/patient in the new policy group and 0.86 U/patient in the st and ard care policy group ( mean difference 0.08;95 % CI [ -0.3 ; 0.2 ] ; P = 0.53 ) . In two hospitals , the new transfusion policy result ed in a RBC reduction of 30 % ( 0.58U RBC/patient ) ( P = 0.17 ) and 41 % ( 0.29 U RBC/patient ) ( P = 0.05 ) respectively . In the third hospital , however , RBC usage increased by 39 % ( 0.31 U RBC/patient ) ( P = 0.02 ) with the new policy , due to a more restrictive st and ard care policy in that hospital . Length of hospital stay was not influenced by either policy . CONCLUSIONS Implementation of a uniform transfusion protocol for elective lower joint arthroplasty patients is feasible , but does not always lead to a RBC reduction . Length of hospital stay was not affected Background : Several studies have indicated that a restrictive erythrocyte transfusion strategy is as safe as a liberal one in critically ill patients , but there is no clear evidence to support the superiority of any perioperative transfusion strategy in patients with cancer . Methods : In a r and omized , controlled , parallel-group , double-blind ( patients and outcome assessors ) superiority trial in the intensive care unit of a tertiary oncology hospital , the authors evaluated whether a restrictive strategy of erythrocyte transfusion ( transfusion when hemoglobin concentration < 7 g/dl ) was superior to a liberal one ( transfusion when hemoglobin concentration < 9 g/dl ) for reducing mortality and severe clinical complications among patients having major cancer surgery . All adult patients with cancer having major abdominal surgery who required postoperative intensive care were included and r and omly allocated to treatment with the liberal or the restrictive erythrocyte transfusion strategy . The primary outcome was a composite endpoint of mortality and morbidity . Results : A total of 198 patients were included as follows : 101 in the restrictive group and 97 in the liberal group . The primary composite endpoint occurred in 19.6 % ( 95 % CI , 12.9 to 28.6 % ) of patients in the liberal- strategy group and in 35.6 % ( 27.0 to 45.4 % ) of patients in the restrictive- strategy group ( P = 0.012 ) . Compared with the restrictive strategy , the liberal transfusion strategy was associated with an absolute risk reduction for the composite outcome of 16 % ( 3.8 to 28.2 % ) and a number needed to treat of 6.2 ( 3.5 to 26.5 ) . Conclusion : A liberal erythrocyte transfusion strategy with a hemoglobin trigger of 9 g/dl was associated with fewer major postoperative complications in patients having major cancer surgery compared with a restrictive strategy Background : Due to the floating of the guideline , there is no evidence -based evaluation index on when to start the blood transfusion for patients with hemoglobin ( Hb ) level between 7 and 10 g/dl . As a result , the trigger point of blood transfusion may be different in the emergency use of the existing transfusion guidelines . The present study was design ed to evaluate whether the scheme can be safely and effectively used for emergency patients , so as to be supported by multicenter and large sample data in the future . Methods : From June 2013 to June 2014 , patients were r and omly divided into the experimental group ( Peri-operative Transfusion Trigger Score of Emergency [ POTTS-E ] group ) and the control group ( control group ) . The between-group differences in the patients ’ demography and baseline information , mortality and blood transfusion-related complications , heart rate , resting arterial pressure , body temperature , and Hb values were compared . The consistency of red blood cell ( RBC ) transfusion st and ards of the two groups of patients with the current blood transfusion guideline , namely the compliance of the guidelines , utilization rate , and per-capita consumption of autologous RBC were analyzed . Results : During the study period , a total of 72 patients were recorded , and 65 of them met the inclusion criteria , which included 33 males and 32 females with a mean age of ( 34.8 ± 14.6 ) years . 50 underwent abdomen surgery , 4 underwent chest surgery , 11 underwent arms and legs surgery . There was no statistical difference between the two groups for demography and baseline information . There was also no statistical differences between the two groups in anesthesia time , intraoperative rehydration , staying time in postanesthetic care unit , emergency hospitalization , postoperative 72 h Acute Physiologic Assessment and Chronic Health Evaluation II scores , blood transfusion-related complications and mortality . Only the POTTS-E group on the 1st postoperative day Hb was lower than group control , P < 0.05 . POTTS-E group was totally ( 100 % ) conformed to the requirements of the transfusion guideline to RBC infusion , which was higher than that of the control group ( 81.25 % ) , P < 0.01 . There were no statistical differences in utilization rates of autologous blood of Output:	The results show that it may not be safe to use a restrictive transfusion threshold of less than 80 g/L in patients with ongoing acute coronary syndrome or chronic cardiovascular disease . Effects on mortality and other outcomes are uncertain .
MS21303	*TASK* the task is to summarize an input biomedical literature in six sentences *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 increasing recognition of the importance of involving patients in decisions on preventive healthcare interventions , little is known about how well patients underst and and utilise information provided on the relative benefits from these interventions . The aim of this study was to explore whether lay people can discriminate between preventive interventions when effectiveness is presented in terms of relative risk reduction ( RRR ) , and whether such discrimination is influenced by presentation of baseline risk . Methods The study was a r and omised cross-sectional interview survey of a representative sample ( n = 1,519 ) of lay people with mean age 59 ( range 40–98 ) years in Denmark . In addition to demographic information , respondents were asked to consider a hypothetical drug treatment to prevent heart attack . Its effectiveness was r and omly presented as RRR of 10 , 20 , 30 , 40 , 50 or 60 percent , and half of the respondents were presented with quantitative information on the baseline risk of heart attack . The respondents had also been asked whether they were diagnosed with hypercholesterolemia or had experienced a heart attack . Results In total , 873 ( 58 % ) of the respondents consented to the hypothetical treatment . While 49 % accepted the treatment when RRR = 10 % , the acceptance rate was 58–60 % for RRR>10 . There was no significant difference in acceptance rates across respondents irrespective of whether they had been presented with quantitative information on baseline risk or not . Conclusion In this study , lay people 's decisions about therapy were only slightly influenced by the magnitude of the effect when it was presented in terms of RRR . The results may indicate that lay people have difficulties in discriminating between levels of effectiveness when they are presented in terms of RRR BACKGROUND It is important that patients are well-informed about risks and benefits of therapies to help them decide whether to accept medical therapy . Different numerical formats can be used in risk communication but It remains unclear how the different formats affect decisions made by real-life patients . AIM To compare the impact of using Prolongation Of Life ( POL ) and Absolute Risk Reduction ( ARR ) information formats to express effectiveness of cholesterol-lowering therapy on patients ' redemptions of statin prescriptions , and on patients ' confidence in their decision and satisfaction with the risk communication . DESIGN AND SETTING Cluster-r and omised clinical trial in general practice s. Thirty-four Danish GPs from 23 practice s participated in a primary care-based clinical trial concerning use of quantitative effectiveness formats for risk communication in health prevention consultations . METHOD GPs were cluster-r and omised ( treating practice s as clusters ) to inform patients about cardiovascular mortality risk and the effectiveness of statin treatment using either POL or ARR formats . Patients ' redemptions of statin prescriptions were obtained from a regional prescription data base . The COMRADE question naire was used to measure patients ' confidence in their decision and satisfaction with the risk communication . RESULTS Of the 240 patients included for analyses , 112 were allocated to POL information and 128 to ARR . Patients redeeming a statin prescription totalled six ( 5.4 % ) when informed using POL , and 32 ( 25.0 % ) when using ARR . The level of confidence in decision and satisfaction with risk communication did not differ between the risk formats . CONCLUSION Patients redeemed statin prescriptions less often when their GP communicated treatment effectiveness using POL compared with ARR Background Different presentations of treatment effects can affect decisions . However , previous studies have not evaluated which presentations best help people make decisions that are consistent with their own values . We undertook a pilot study to compare different methods for doing this . Methods and Findings We conducted an Internet-based r and omized trial comparing summary statistics for communicating the effects of statins on the risk of coronary heart disease ( CHD ) . Participants rated the relative importance of treatment consequences using visual analogue scales ( VAS ) and category rating scales ( CRS ) with five response options . We r and omized participants to either VAS or CRS first and to one of six summary statistics : relative risk reduction ( RRR ) and five absolute measures of effect : absolute risk reduction , number needed to treat , event rates , tablets needed to take , and natural frequencies ( whole numbers ) . We used logistic regression to determine the association between participants ' elicited values and treatment choices . 770 participants age 18 or over and literate in English completed the study . In all , 13 % in the VAS-first group failed to complete their VAS rating , while 9 % of the CRS-first group failed to complete their scoring ( p = 0.03 ) . Different ways of weighting the elicited values had little impact on the analyses comparing the different presentations . Most ( 51 % ) preferred the RRR compared to the other five summary statistics ( 1 % to 25 % , p = 0.074 ) . However , decisions in the group presented the RRR deviated substantially from those made in the other five groups . The odds of participants in the RRR group deciding to take statins were 3.1 to 5.8 times that of those in the other groups across a wide range of values ( p = 0.0007 ) . Participants with a scientific background , who were more numerate or had more years of education were more likely to decide not to take statins . Conclusions Internet-based trials comparing different presentations of treatment effects are feasible , but recruiting participants is a major challenge . Despite a slightly higher response rate for CRS , VAS is preferable to avoid approximation of a continuous variable . Although most participants preferred the RRR , participants shown the RRR were more likely to decide to take statins regardless of their values compared with participants who were shown any of the five other summary statistics . Trial Registration Controlled-Trials.com IS RCT # # # # Summary box Measurement of blood pressure is an iconic part of modern medicine . Over the past century , life insurers , public health organisations , and prospect i ve studies , including the Framingham Heart Study , have established the relation between increased blood pressure and long term morbidity and mortality.1 About Graphic representation was used to explore to what extent the number needed to treat ( NNT ) conveys the appropriate notion of benefit for the individual patient in interventions aim ed at delaying adverse events . A sample of the Danish population ( n = 675 ) was interviewed face to face , and asked whether they would consent to a hypothetical drug that reduces the risk of heart attack . The benefit of the drug was expressed in terms of NNT and was r and omly set at 10 , 25 , 50 , 100 , 200 , and 400 . NNT does not convey information on the proportion of patients being helped by an intervention or the size of the delay of the adverse event intended to be prevented . The proportion of people consenting to the hypothetical drug was about 80 % , irrespective of NNT , and some of those who rejected the drug misinterpreted the meaning of NNT . Lay people may have difficulties in underst and ing the meaning of NNT , and clinicians may do well to use the NNT with caution until more is known about how patients comprehend it Background Shared decision-making and patients ’ choice of interventions are areas of increasing importance , not least seen in the light of the fact that chronic conditions are increasing , interventions considered important for public health , and still non-acceptance of especially risk-reducing treatments of cardiovascular diseases ( CVD ) is prevalent . A better underst and ing of patients ’ medication-taking behavior is needed and may be reached by study ing the reasons why people accept or decline medication recommendations . The aim of this paper was to identify factors that may influence people ’s decisions and reasoning for accepting or declining a cardiovascular preventive medication offer . Methods From a r and om sample of 4,000 people aged 40–59 years in a Danish population , 1,169 participants were asked to imagine being at increased risk of cardiovascular disease and being offered a preventive medication . After receiving ‘ complete ’ information about effectiveness of the medication they were asked whether they would accept medication . Finally , they were asked about reasons for the decision . Results A total of 725 ( 67 % ) of 1,082 participants accepted the medication offer . Even quite large effects of medication ( up to 8 percentage points absolute risk reduction ) had a smaller impact on acceptance to medication than personal experience with cardiovascular disease . Furthermore , increasing age of the participant and living with a partner were significantly associated with acceptance . Some 45 % of the respondents accepting justified their choice as being for health reasons , and they were more likely to be women , live alone , have higher income and higher education levels . Among those who did not accept the medication offer , 56 % indicated that they would rather prefer to change lifestyle . Conclusions Medication effectiveness seems to have a moderate influence on people ’s decisions to accept preventive medication , while factors such as personal experience with cardiovascular disease may have an equally strong or stronger influence , indicating that practitioners could do well to carefully identify the reasons for their patients ’ treatment decisions Background For shared decision making doctors need to communicate the effectiveness of therapies such that patients can underst and it and discriminate between small and large effects . Previous research indicates that patients have difficulties in underst and ing risk measures . This study aim ed to test the hypothesis that lay people may be able to discriminate between therapies when their effectiveness is expressed in terms of postponement of an adverse disease event . Methods In 2004 a r and om sample of 1,367 non-institutionalized Danes aged 40 + was interviewed in person . The participants were asked for demographic information and asked to consider a hypothetical preventive drug treatment . The respondents were r and omized to the magnitude of treatment effectiveness ( heart attack postponement of 1 month , 6 months , 12 months , 2 years , 4 years and 8 years ) and subsequently asked whether they would take such a therapy . They were also asked whether they had hypercholesterolemia or had experienced a heart attack . Results In total 58 % of the respondents consented to the hypothetical treatment . The proportions accepting treatment were 39 % , 52 % , 56 % , 64 % , 67 % and 73 % when postponement was 1 month , 6 months , 12 months , 2 years , 4 years and 8 years respectively . Participants who thought that the effectiveness information was difficult to underst and , were less likely to consent to therapy ( p = 0.004 ) . Conclusion Lay people can discriminate between levels of treatment effectiveness when they are presented in terms of postponement of an adverse event . The results indicate that such postponement is a comprehensible measure of effectiveness Background There is uncertainty about how GPs should convey information about treatment effectiveness to their patients in the context of cardiovascular disease . Hence we study the concordance of decisions based on one of four single information formats for treatment effectiveness with subsequent decisions based on all four formats combined with a pictorial representation . Methods A r and omized study comprising 1,169 subjects aged 40–59 in Odense , Denmark . Subjects were r and omized to receive information in terms of absolute risk reduction ( ARR ) , relative risk reduction ( RRR ) , number needed to treat ( NNT ) , or prolongation of life ( POL ) without heart attack , and were asked whether they would consent to treatment . Subsequently the same information was conveyed with all four formats jointly accompanied by a pictorial presentation of treatment effectiveness . Again , subjects should consider consent to treatment . Results After being informed about all four formats , 52%–79 % of the respondents consented to treatment , depending on level of effectiveness and initial information format . Overall , ARR gave highest concordance , 94 % ( 95 % confidence interval ( 91 % ; 97 % ) ) between initial and final decision , but ARR was not statistically superior to the other formats . Conclusion Decisions based on ARR had the best concordance with decisions based on all four formats and pictorial representation , but the difference in concordance between the four formats was small , and it is unclear whether respondents fully understood the information they received BACKGROUND The number needed to treat ( NNT ) has been promoted as the preferred effect measure when patients and physicians share decision making . Our aim was to explore the impact of the NNT on laypeople 's decisions about preventive drug therapies . METHODS Two thous and subjects were selected for the survey ; 1201 ( 60 % ) responded for a representative sample of the Norwegian population . Respondents were allocated to scenarios with r and om combinations of a disease to be prevented , drug treatment costs , and effect size in terms of NNT . They were interviewed about their hypothetical consent to the therapy , then r and omized to different interpretations of NNT and asked to reconsider their initial responses . RESULTS The proportions consenting varied from 76 % when the NNT was 50 to 67 % when the NNT was 1600 ( P for trend = .06 ) . When faced with the prospect of avoiding lethal disease , stroke , myocardial infa rct ion , or hip fracture , the proportions consenting were 84 % , 76 % , 68 % , and 53 % , respectively ( P<.01 ) . Across different treatment costs ( $ 37 , $ 68 , $ 162 , and $ 589 ) the proportions consenting varied from 78 % to 61 % ( P for trend < .01 ) . Twenty-four percent of the respondents changed their decision when informed about how to interpret the NNT , and 93 % of those switched from positive to negative decisions , regardless of the magnitude of NNT . CONCLUSIONS Respondents ' decisions were influenced by the type of disease to be prevented and the cost of the intervention , but not by the effect size in terms of NNT . This suggests that NNT is difficult to underst and and that other effect formats should be considered for shared decision making Background We conducted an Internet-based r and omized trial comparing three valence framing presentations of the benefits of antihypertensive medication in preventing cardiovascular disease ( CVD ) for people with newly diagnosed hypertension to determine which framing presentation result ed in choices most consistent with participants ' values . Methods and Findings In this second in a series of televised trials in cooperation with the Norwegian Broadcasting Company , adult volunteers rated the relative importance of the consequences of taking antihypert Output:	Conclusions Many patients require a substantial risk reduction before they consider taking a daily medication worthwhile , even when the medication is described as being side effect free and costless
MS21304	*TASK* the task is to summarize an input biomedical literature in six sentences *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 develop a short cognitive test for screening mild cognitive impairment ( MCI ) in Hong Kong Chinese older adults . Methods : The Chinese Abbreviated MCI ( CAMCI ) test was developed with a multistage process . In phase 1 , a short version of the cognitive test comprising a 1-min animal fluency test and a 10-min delayed word list recall was developed and tested in 578 volunteers ( community-dwelling active elderly persons ) . In phase 2 , the CAMCI test was vali date d in an independent and r and omly recruited sample of 459 participants in a community survey . Additionally , the predictive significance of the CAMCI test was evaluated in a group of 196 subjects assessed in phase 1 for conversion to clinical dementia at 20 months ’ follow-up . The discriminating power of the CAMCI test in differentiating MCI from normal control ( NC ) and mildly demented subjects was compared with Mini Mental State Examination ( MMSE ) and Alzheimer ’s Disease Assessment Scale-Cognitive ( ADAS-Cog ) subscales . Results : The CAMCI test was found to have high discriminating power in differentiating NC from MCI and mildly demented subjects in the phase 1 volunteer sample . The receiver operating characteristics ( ROC ) revealed an area under the curve ( AUC ) of 0.91 . The ROC were further vali date d in the phase 2 sample . The AUC of the CAMCI test was compared with MMSE and ADAS-Cog subscales . The short MCI test was comparable to the ADAS-Cog subscale in discriminating NC from MCI and demented subjects ( χ2 test , p = n.s . ) . Logistic regression analysis was carried out to determine significant baseline predictors for conversion to dementia at phase 3 follow-up . Both ADAS-Cog total [ Exp(B ) = 1.115 , p = 0.028 ] and CAMCI [ Exp(B ) = 0.88 , p = 0.045 ] scores were significant predictors for dementia status at follow-up . Conclusion : The CAMCI test is able to discriminate NC from MCI and mild dementia in Hong Kong Chinese older adults . Its potential for large-scale community screening for early detection of cognitive impairment in late life should be emphasized and explored Background / Aims : To prospect ively follow up a group of amnesic patients at risk for Alzheimer ’s disease ( AD ) , to characterize a group of patients whose features were intermediate between amnesic mild cognitive impairment ( aMCI ) and probable AD , prodromal AD ( Prd-AD ) , and to investigate if these patients were at higher risk for AD conversion . Methods : A total of 109 subjects were assessed by neuropsychological evaluation and by 1H magnetic resonance spectroscopy ( 1H-MRS ) : 27 controls , and 16 aMCI , 34 probable AD and 32 Prd-AD patients . Results : Episodic memory and frontal test scores result ed lower in Prd-AD compared to aMCI patients . Prd-AD patients obtained significantly higher scores than AD ones in language , perception , praxis and frontal functions . Although Prd-AD and AD patients had distinct 1H-MRS features from aMCI ones , there were no 1H-MRS differences between Prd-AD and AD patients . The AD annual conversion rate after 1 year of follow-up for Prd-AD ( 57.1 % ) was higher than in aMCI patients ( 20 % ; p < 0.01 ) . A logistic regression , in which all amnesic patients were treated as a single group , showed that the Visual Memory Test was a significant neuropsychological predictor for AD conversion . Conclusions : Prd-AD patients are a clinical ly distinguishable group , with distinct neuropsychological and 1H-MRS features and a higher conversion rate to probable AD than aMCI patients BACKGROUND Subjects with a mild cognitive impairment ( MCI ) have a memory impairment beyond that expected for age and education yet are not demented . These subjects are becoming the focus of many prediction studies and early intervention trials . OBJECTIVE To characterize clinical ly subjects with MCI cross-sectionally and longitudinally . DESIGN A prospect i ve , longitudinal inception cohort . SETTING General community clinic . PARTICIPANTS A sample of 76 consecutively evaluated subjects with MCI were compared with 234 healthy control subjects and 106 patients with mild Alzheimer disease ( AD ) , all from a community setting as part of the Mayo Clinic Alzheimer 's Disease Center/Alzheimer 's Disease Patient Registry , Rochester , Minn. MAIN OUTCOME MEASURES The 3 groups of individuals were compared on demographic factors and measures of cognitive function including the Mini-Mental State Examination , Wechsler Adult Intelligence Scale-Revised , Wechsler Memory Scale-Revised , Dementia Rating Scale , Free and Cued Selective Reminding Test , and Auditory Verbal Learning Test . Clinical classifications of dementia and AD were determined according to the Diagnostic and Statistical Manual of Mental Disorders , Revised Third Edition and the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer 's Disease and Related Disorders Association criteria , respectively . RESULTS The primary distinction between control subjects and subjects with MCI was in the area of memory , while other cognitive functions were comparable . However , when the subjects with MCI were compared with the patients with very mild AD , memory performance was similar , but patients with AD were more impaired in other cognitive domains as well . Longitudinal performance demonstrated that the subjects with MCI declined at a rate greater than that of the controls but less rapidly than the patients with mild AD . CONCLUSIONS Patients who meet the criteria for MCI can be differentiated from healthy control subjects and those with very mild AD . They appear to constitute a clinical entity that can be characterized for treatment interventions Background : Magnetic resonance diffusion tensor imaging ( DTI ) shows promise in the early detection of microstructural pathophysiological changes in the brain . Objectives : To measure microstructural differences in the brains of participants with amnestic mild cognitive impairment ( MCI ) compared with an age-matched control group using an optimised DTI technique with fully automated image analysis tools and to investigate the correlation between diffusivity measurements and neuropsychological performance scores across groups . Methods : 34 participants ( 17 participants with MCI , 17 healthy elderly adults ) underwent magnetic resonance imaging (MRI)-based DTI . To control for the effects of anatomical variation , diffusion images of all participants were registered to st and ard anatomical space . Significant statistical differences in diffusivity measurements between the two groups were determined on a pixel-by-pixel basis using gaussian r and om field theory . Results : Significantly raised mean diffusivity measurements ( p<0.001 ) were observed in the left and right entorhinal cortices ( BA28 ) , posterior occipital – parietal cortex ( BA18 and BA19 ) , right parietal supramarginal gyrus ( BA40 ) and right frontal pre central gyri ( BA4 and BA6 ) in participants with MCI . With respect to fractional anisotropy , participants with MCI had significantly reduced measurements ( p<0.001 ) in the limbic parahippocampal subgyral white matter , right thalamus and left posterior cingulate . Pearson ’s correlation coefficients calculated across all participants showed significant correlations between neuropsychological assessment scores and regional measurements of mean diffusivity and fractional anisotropy . Conclusions : DTI-based diffusivity measures may offer a sensitive method of detecting subtle microstructural brain changes associated with pre clinical Alzheimer ’s disease Summary OBJECTIVE : The goals of this study were to determine the annual conversion rate to Alzheimer disease ( AD ) among patients reporting memory problems , including a subgroup with amnestic mild cognitive impairment ( aMCI ) , and to investigate the predictive value of neurocognitive testing for future dementia . METHODS : A prospect i ve study was carried out in an outpatient memory clinic . One hundred and seven patients underwent a clinical examination and completed a battery of st and ard cognitive tests at study entry and two years later . The conversion rate to clinical ly manifested AD two years later was investigated , and sensitivity , specificity , receiver operating characteristics ( AUC ) , positive predictive value and negative predictive value for each neuropsychological test were determined . RESULTS : We found an annual rate of conversion to AD of 6.5 % among patients reporting memory decline in the setting of our clinic . Specifically , patients with aMCI had an annual conversion rate of approximately 20 % . The annual conversion rate for patients reporting memory problems but showing no memory deficit at memory testing was approximately 3 % . Receiver operating characteristics ( AUC ) of the neuropsychological tests ranged from 0.60 to 0.94 . CONCLUSIONS : Patients with aMCI have 8.6-fold higher odds of developing AD compared with patients without evident memory impairment on neuropsychological testing . Although the risk of developing AD among patients without objective memory decline is small , some patients in this group still convert to AD , and therefore , close clinical monitoring of patients is necessary . ZusammenfassungZIEL : Ziel der vorliegenden Studie war die Bestimmung der jährlichen Konversionsrate von Patienten mit subjektiver Gedächtnisbeeinträchtigung zur Alzheimerkrankheit unter Berücksichtigung der amnestischen Milden Kognitiven Störung ( aMCI ) . Die Wertigkeit zur Vorhersage der Konversion durch einzelne neuropsychologische Testverfahren wurde ebenfalls untersucht . METHOD IK : I m Rahmen einer Gedächtnisambulanz wurde eine prospektive Studie durchgeführt . 107 Patienten wurden in die Studie inkludiert . Alle Patienten durchliefen eine neurologische und eine neuropsychologische Untersuchung am Beginn der Studie und nach zwei Jahren am Ende der Studie . Einerseits wurde die Konversionsrate zur Alzheimerkrankheit untersucht , und and erseits wurden einige Kennwerte der Kriteriumsvalidität ( Sensitivität , Spezifität , Receiver Operating Characteristics [ AUC ] , Positive Predictive Value , Negative Predictive Value ) einzelner neuropsychologischer Testverfahren zur Vorhersage der Alzheimerkrankheit bestimmt . RESULT AT : Wir f and en eine jährliche Konversionsrate von 6,5 % für Patienten , die eine Beeinträchtigung der Gedächtnisfunktionen berichteten . Patienten mit aMCI hatten eine jährliche Konversionsrate von ungefähr 20 % . Die jährliche Konversionsrate von Patienten mit subjektiver Gedächtnisbeeinträchtigung ohne testpsychologisch nachweisbare Gedächtnistörung lag bei ungefähr 3 % . Receiver operating characteristics ( AUC ) für einzelne neuropsychologische Verfahren lagen zwischen 0,60 und 0,94 . KONKLUSION : Patienten mit aMCI haben , i m Vergleich zu Patienten ohne neuropsychologisch fassbare Gedächtnisstörung , eine 8,6-fache Wahrscheinlichkeit , innerhalb von zwei Jahren eine klinisch manifeste Alzheimerkrankheit zu entwickeln . Obwohl die Wahrscheinlichkeit für Patienten ohne neuropsychologisch fassbare Gedächtnisstörung , innerhalb von zwei Jahren eine Alzheimerkrankheit zu entwickeln , gering ist , konvertieren einige wenige Patienten doch zur Alzheimerkrankheit . Engmaschige Kontrolluntersuchungen sind deshalb notwendig Objective . To design a brief cognitive screener with acceptable sensitivity and specificity for identifying subjects with cognitive impairment Design . Cohort one is assembled from a community-based survey coupled with a second-stage diagnostic evaluation using formal diagnostic criteria for dementia . Cohort two is assembled from referrals to a specialty clinic for dementing disorders that completed the same diagnostic evaluation . Setting . Urban neighborhoods in Indianapolis , Indiana and the Indiana Alzheimer Disease Center . Patients . Cohort one consists of 344 community-dwelling black persons identified from a r and om sample of 2212 black persons aged 65 and older residing in Indianapolis ; cohort two consists of 651 subject referrals to the Alzheimer Disease Center . Measurements . Formal diagnostic clinical assessment s for dementia including scores on the Mini-mental state examination ( MMSE ) , a six-item screener derived from the MMSE , the Blessed Dementia Rating Scale ( BDRS ) , and the Word List Recall . Based on clinical evaluations , subjects were categorized as no cognitive impairment , cognitive impairment-not demented , or demented . Results . The mean age of the community-based sample was 74.4 years , 59.4 % of the sample were women , and the mean years of education was 10.1 . The prevalence of dementia in this sample was 4.3 % and the prevalence of cognitive impairment was 24.6 % . Using a cut-off of three or more errors , the sensitivity and specificity of the six-item screener for a diagnosis of dementia was 88.7 and 88.0 , respectively . In the same sample , the corresponding sensitivity and specificity for the MMSE using a cut-off score of 23 was 95.2 and 86.7 . The performance of the two scales was comparable across the two population s studied and using either cognitive impairment or dementia as the gold st and ard . An increasing number of errors on the six-item screener is highly correlated with poorer scores on longer measures of cognitive impairment . Conclusions . The six-item screener is a brief and reliable instrument for identifying subjects with cognitive impairment and its diagnostic properties are comparable to the full MMSE . It can be administered by telephone or face-to-face interview and is easily scored by a simple summation of errors BACKGROUND Mild cognitive impairment ( MCI ) is considered to be a transitional Output:	Sensitivities of the full domain measures were universally high , but information about their specificity against psychiatric and non-progressive neurological conditions and predictive validity is lacking . Several cognitive screening instruments afford the clinician the ability to detect MCI , early AD , and in some cases non-AD dementia , but they can not currently be used to make reliable inferences about the course and eventual outcome of MCI
MS21305	*TASK* the task is to summarize an input biomedical literature in six sentences *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 compared the rate of leg ulcer recurrence using two types of compression stockings and examined the factors underlying Patients with recently healed leg ulceration were entered into a study of leg ulcer recurrence . In all , 188 patients [ 69 % women , mean age = 72 ( SD = 12 ) years ] were entered into the study , of whom 166 were considered suitable for ready-made stockings and were r and omized to one of two class II below-knee compression stockings and followed for at least 18 months . The remaining patients required either made-to-measure stockings ( 5 ) or could not tolerate stockings owing to friable skin and were treated by other methods ( 17 ) . Overall cumulative recurrence rate was 26 % after 1 year and 31 % at 18 months . Independent risk factors for ( RR = 2.34 , p = 0.021 ) and unsuitability for stockings ( RR = 2.52 , p = 0.013 ) . The r and omized groups had similar stockings , 25 ( 15 % ) could not put their stockings on at all and 43 ( 26 % ) were only able to put them on with great difficulty . The two stocking types differed significantly in this regard when analysed for trend The effect of elastic compression on venous flow in the legs provided by carefully fitted stockings has been measured by a venographic technic . The stocking used provides a gradually decreasing compression from ankle to groin . Clearance of stagnant blood from behind venous valves is clearly improved and the differences observed are statistically highly significant . These data suggest that the routine use of carefully fitted compression stockings will result in a decreased incidence of deep vein thrombosis ( DVT ) and provide a singularly safe , convenient , and noninvasive method of prophylaxis . Evidence presented suggests that at least two investigators have failed to show a decreased incidence of DVT in limbs subjected to elastic compression because the method of compression was inadequate Output:	Both trials reported that not wearing compression hosiery was strongly associated with ulcer recurrence and this is circumstantial evidence that compression reduces ulcer recurrence . This is circumstantial evidence of the benefit of compression in reducing recurrence . Recurrence rates may be lower in high compression hosiery than in medium compression hosiery and therefore patients should be offered the strongest compression with which they can comply .
MS21306	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Benefits of community-based whole-body vibration ( WBV ) as a mode of exercise training for people with chronic obstructive pulmonary disease ( COPD ) have not been investigated . The low skill dem and of WBV may enhance habitual sustainability to physical activity by people with COPD , provided efficacy of WBV can be established . The purpose of this trial was to compare a community-based WBV intervention with a sham WBV ( SWBV ) intervention and monitor exacerbations , exercise tolerance , and functional performance of the lower limbs of people with COPD . Methods Community-dwelling adults with a GOLD clinical diagnosis of COPD were recruited to the trial . This was a Phase II efficacy trial with crossover to sham intervention interspersed with two-week washout . Each six-week intervention consisted of two sessions per week of either WBV or SWBV . The interventions were completed in the home of each participant under supervision . The outcome measures were selected psychological ( perceived dyspnoea ) and physiological ( heart rate and oxygen saturation ) responses to exercise , simulated activities of daily living ( timed-up- and got test and 5-chair st and s test ) , and selected kinematic variables of gait across the 14-week trial . Results Sixteen adults with stable COPD were recruited to the trial . No exacerbations were reported during the WBV or SWBV interventions . After WBV , performance of activities of daily living ( ADLs ) and gait improved ( p ≤ 0.05 ) , while there was no change after SWBV ( p > 0.05 ) . Despite five withdrawals during the washout period , a 100 % compliance to each six-week intervention was noted . Conclusions Results showed that WBV did not exacerbate symptoms of COPD that can be associated with physical inactivity . The WBV intervention improved tests to simulate ADLs such as rising from a chair , turning , and walking gait with greater effect than a SWBV intervention . If a placebo effect was systemic to the WBV intervention , the effect was negligible . As a st and alone community-based intervention , WBV was an efficacious mode of exercise training for people with stable COPD that did not negatively effect exercise tolerance or exacerbate the disease , while concurrently improving functional performance of the lower limbs . Trial registration Australian and New Zeal and Clinical Trials Registry ACTRN12612000508875 Background Exercise intolerance is a common development in patients with chronic obstructive pulmonary disease ( COPD ) . There is little data on the use of an isolated program using vibration platform training on functional capacity in these patients , which is an area that deserves investigation . Aim To investigate the effect of training on a vibrating platform ( whole-body vibration [ WBV ] ) on functional performance and quality of life of subjects with COPD . Methods A r and omized controlled crossover pilot study with eleven subjects with COPD ( forced expiratory volume in 1 second [FEV1]% predicted = 14.63±11.14 ; forced vital capacity [FVC]% predicted = 48.84±15.21 ; FEV1/FVC = 47.39±11.63 ) underwent a 12-week WBV training program . Participants were r and omized into the intervention group ( IG ) undergoing three sessions per week for a total of 12 weeks and control group ( CG ) without intervention . We evaluated the 6-minute walk test ( 6MWT ) , distance walked ( DW ) , duration of the walk ( TW ) , and index of perceived exertion ( IPE ) , quality of life using St George ’s Respiratory Question naire ( SGRQ ) and developed a 12-week program of training on a vibrating platform . Results The mean age was 62.91±8.82 years old ( 72.7 % male ) . The DW increased at the end of training with a difference between groups of 75 m ; all domains of the SGRQ improved at the end of training . The effect size Cohen ’s d ranged from small to large for all the measured results . Conclusion These preliminary results suggest that WBV may potentially be a safe and feasible way to improve functional capacity in the 6MWT of patients with COPD undergoing a training program on the vibrating platform as well as in all domains of the SGRQ quality of life . However , further studies with a larger number of patients are needed to establish the long-term effect on functional capacity and quality of life in these patients Background The potential of whole-body vibration ( WBV ) as a mode of dyspnoea free physical activity for people with chronic obstructive pulmonary disease ( COPD ) is unknown among community-based setting s. Furthermore , the acute effects of WBV on people with COPD have not been profiled in community-based setting s. The aim of this community-based proof-of-concept trial was to describe acute effects of WBV by profiling subjective and objective responses to physical activity . Findings Seventeen community-dwelling older adults with COPD were recruited to participate in two sessions ; WBV and sham WBV ( SWBV ) . Each session consisted of five one-minute bouts interspersed with five one-minute passive rest periods . The gravitational force was ~2.5 g for WBV and ~0.0 g for SWBV . Reliability of baseline dyspnoea , heart rate , and oxygen saturation was first established and then profiled for both sessions . Acute responses to both WBV and SWBV were compared with repeated measures analysis of variance and repeated contrasts . Small changes in dyspnoea and oxygen saturation lacked subjective and clinical meaningfulness . One session of WBV and SWBV significantly increased heart rate ( p ≤ 0.02 ) , although there was no difference among WBV and SWBV ( p = 0.67 ) . Conclusions This community-based proof-of-concept trial showed that a session of WBV can be completed with the absence of dyspnoea for people with COPD . Furthermore , there were no meaningful differences among WBV and SWBV for heart rate and oxygen saturation . There is scope for long-term community-based intervention research using WBV given the known effects of WBV on peripheral muscle function and functional independence BACKGROUND Patients with chronic obstructive pulmonary disease ( COPD ) often present with severe acute exacerbations requiring hospital treatment . However , little is known about the prognostic consequences of these exacerbations . A study was undertaken to investigate whether severe acute exacerbations of COPD exert a direct effect on mortality . METHODS Multivariate techniques were used to analyse the prognostic influence of acute exacerbations of COPD treated in hospital ( visits to the emergency service and admissions ) , patient age , smoking , body mass index , co-morbidity , long term oxygen therapy , forced spirometric parameters , and arterial blood gas tensions in a prospect i ve cohort of 304 men with COPD followed up for 5 years . The mean ( SD ) age of the patients was 71 ( 9 ) years and forced expiratory volume in 1 second was 46 (17)% . RESULTS Only older age ( hazard ratio ( HR ) 5.28 , 95 % CI 1.75 to 15.93 ) , arterial carbon dioxide tension ( HR 1.07 , 95 % CI 1.02 to 1.12 ) , and acute exacerbations of COPD were found to be independent indicators of a poor prognosis . The patients with the greatest mortality risk were those with three or more acute COPD exacerbations ( HR 4.13 , 95 % CI 1.80 to 9.41 ) . CONCLUSIONS This study shows for the first time that severe acute exacerbations of COPD have an independent negative impact on patient prognosis . Mortality increases with the frequency of severe exacerbations , particularly if these require admission to hospital Disease progression in cystic fibrosis ( CF ) leads to muscle wasting and loss of muscle function . The aim of this prospect i ve pilot study was to evaluate the effects of whole body vibration ( WBV ) on muscle function in adult patients with CF . Ten patients ( three males ; seven females ) of the CF Center Cologne , Germany , have completed the 3-month study ( age : 24–47 years ; forced expiratory volume in 1 s ( FEV1 ) 17–109 % predicted ( 49±29 ) and body mass index ( BMI ) 16.6–24.4 kg/m2 ( 19.3±2.5 ) . WBV was provided by a vibration platform ( Galileo 2000 ) . The patients were st and ing in an upright position receiving vertical vibration of frequencies between 20 and 25 Hz . The vibration exercise evokes muscle contractions via stretch reflexes improving muscular activity . The training schedule consisted of three 3-min sessions twice a day , 5 days per week for 3 months . Every 4 weeks the following tests were carried out : FEV1 , forced vital capacity ( FVC ) , BMI , chair-rising test ( CRT ) , one-leg and two-leg jump test as well as maximal isometric grip force . The study has been approved by the local ethics committee . After 3 months of WBV all parameters in the CRT significantly improved : chair-rising time ( P=0.03 ) , maximal force ( P=0.02 ) , maximal power ( P=0.01 ) as well as velocity ( P=0.02 ) . The peak jump force ( P=0.02 ) and velocity ( P=0.01 ) of the two-leg jump significantly improved . Parameters in the one-leg jump as well as maximal isometric grip force showed no significant improvement . Weight and BMI showed a slightly positive trend whereas FEV1 and FVC did not significantly change . Any change in mechanographic parameters did not correlate with FEV1 or FVC in this study . These results demonstrate that WBV can improve muscle function in CF patients Background Patients with stable COPD show improvements in exercise capacity and muscular function after the application of whole body vibration . We aim ed to evaluate whether this modality added to conventional physiotherapy in exacerbated hospitalised COPD patients would be safe and would improve exercise capacity and quality of life . Methods 49 hospitalised exacerbated COPD patients were r and omized ( 1:1 ) to undergo physiotherapy alone or physiotherapy with the addition of whole body vibration . The primary endpoint was the between-group difference of the 6-minute walking test ( day of discharge – day of admission ) . Secondary assessment s included chair rising test , quality of life , and serum marker analysis . Results Whole body vibration did not cause procedure-related adverse events . Compared to physiotherapy alone , it led to significantly stronger improvements in 6-minute walking test ( 95.55 ± 76.29 m vs. 6.13 ± 81.65 m ; p = 0.007 ) and St. Georges Respiratory Question naire ( -6.43 ± 14.25 vs. 5.59 ± 19.15 , p = 0.049 ) . Whole body vibration increased the expression of the transcription factor peroxisome proliferator receptor gamma coactivator-1-α and serum levels of irisin , while it decreased serum interleukin-8 . Conclusion Whole body vibration during hospitalised exacerbations did not cause procedure-related adverse events and induced clinical ly significant benefits regarding exercise capacity and health-related quality of life that were associated with increased serum levels of irisin , a marker of muscle activity . Trial registration German Clinical Trials Register DRKS00005979 . Registered 17 March 2014 Background Chronic obstructive pulmonary disease ( COPD ) is a respiratory condition characterised by dyspnoea , excessive sputum production , chronic cough , bronchitis and emphysema . Functionally , exercise tolerance is poor for people with COPD and is linked to difficulty in performing daily tasks . More specifically , exercise difficulties are due partly to dyspnoea and lower limb skeletal muscle dysfunction . The benefit of exercise that does not exacerbate the disease while improving exercise tolerance is salient . Whole-body vibration ( WBV ) is a mode of physical activity known to improve muscular function of the lower limbs , yet efficacy has not been investigated for a WBV intervention conducted in a home-based setting for people with COPD . Methods / design This clinical ly registered trial is a non-r and omised placebo cross-over intervention based in the home of each participant ( ACTRN12612000508875 ) . Participants diagnosed with COPD will complete a six-week WBV intervention and then after a two-week washout period , will complete a six-week placebo training intervention . Participants will complete sessions twice a week . The duration of the trial is 14 weeks . Community-dwelling older adults with COPD will provide informed voluntary consent to participate . Outcome measures will include immediate , acute , and long-term responses to exercise . Discussion Quantifying responses to WBV among people with COPD will allow discussion of efficacy of WBV as a mode of physical activity . The skill required by the participant to perform physical activity with WBV is not dem and ing and may enhance habitual sustainability . The results of this trial could be used to support further research in both clinical and community setting s . Trial registration Australian New Zeal and Clinical Trials Registry ( ANZCTR12612000508875 Background To examine the effects of whole body vibration ( WBV ) exposure on muscle function in children with Cystic Fibrosis ( CF ) . Non-r and omised controlled cross-over trial . Methods The setting was home-based WBV exposure . The participants were children ( 8 - 15 years ) with CF ( n = 7 ) . Output:	Whole body vibration led to significant improvements in functional exercise capacity measured with six minutes walking test . Nearly no adverse events were observed . Conclusion : Whole body vibration may improve functional exercise capacity and quality of life in people with chronic obstructive pulmonary disease . There was insufficient evidence to prove the effects of whole body vibration on pulmonary function
MS21307	*TASK* the task is to summarize an input biomedical literature in six sentences *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 ] This study investigates whether cognition , balance and dual task performance in institutionalized older adults improves by a virtual reality dual task training . [ Subjects and Methods ] R and omized controlled trial ; Twenty institutionalized older adults with mild cognitive impairment ( 13 female , 7 male ; average age , 87.2 ± 5.96 years ) were r and omized to the intervention ( i.e. Virtual reality dual-task training using the BioRescue ) or control group ( no additional training ) . The intervention group took part in a 6-week training program while the elderly in the control group maintained their daily activities . Balance was measured with the Instrumented Timed Up- and -Go Test with and without a cognitive task . The Observed Emotion Rating Scale and Intrinsic Motivation Inventory were administered to evaluate the emotions and motivation regarding the exergaming program . [ Results ] The intervention group improved significantly on the total Timed Up- and -Go duration and the turn-to-sit duration during single-task walking in comparison to the control group who received no additional training . Participants found the virtual reality dual task training pleasant and useful for their concentration , memory and balance . Pleasure and alertness were the two emotions which were mostly seen during the intervention . [ Conclusion ] The BioRescue is a pleasant and interesting treatment method , well suited for institutionalized older adults in need of lifelong physical therapy The aim of the current study was to compare the effectiveness of two types of cognitive training in 60 older adults with mild cognitive impairment by assessing the impact on functional activities , quality of life ( QOL ) , and various cognitive functions . The primary outcomes were functional activity level and QOL . The secondary outcome was cognitive examination . Group assignment was r and om . Group A ( n = 30 ) underwent CogniPlus , a computer-based , cognitive training . Group B ( n = 30 ) underwent classical group-based cognitive training . Both programs comprised two 30-minute sessions per week for 10 weeks . After training , group A had better QOL ( p < 0.001 , effect size [ ES ] = 0.69 ) and better attention ( increased load score , p < 0.05 , ES = -0.23 ; errors , p < 0.001 , ES = -0.47 ) ; however , there were no group differences in functional activity level . Group A demonstrated larger improvements in QOL and attention than group B ( i.e. , classical cognitive training ) , but the transfer to functional activities was the same between groups . [ Res Gerontol Nurs . 2017 ; 10(4):172 - 180 . ] Abstract Background Cognitive training is effective in patients with mild cognitive impairment but does not typically address the motivational deficits associated with older population s with memory difficulties . Methods We conducted a r and omized controlled trial of cognitive training using a novel memory game on an iPad in 42 patients with a diagnosis of amnestic mild cognitive impairment assigned to either the cognitive training ( n=21 ; 8 hours of gameplay over 4 weeks ) or control ( n=21 ; clinic visits as usual ) groups . Results Significant time-by-pattern-by-group interactions were found for cognitive performance in terms of the number of errors made and trials needed on the Cambridge Neuropsychological Test Automated Battery Paired Associates Learning task ( P=.044 ; P=.027 ) . Significant time-by-group interactions were also found for the Cambridge Neuropsychological Test Automated Battery Paired Associates Learning first trial memory score ( P=.002 ) , Mini-Mental State Examination ( P=.036 ) , the Brief Visuospatial Memory Test ( P=.032 ) , and the Apathy Evaluation Scale ( P=.026 ) . Within-group comparisons revealed highly specific effects of cognitive training on episodic memory . The cognitive training group maintained high levels of enjoyment and motivation to continue after each hour of gameplay , with self-confidence and self-rated memory ability improving over time . Conclusions Episodic memory robustly improved in the cognitive training group . “ Gamified ” cognitive training may also enhance visuospatial abilities in patients with amnestic mild cognitive impairment . Gamification maximizes engagement with cognitive training by increasing motivation and could complement pharmacological treatments for amnestic mild cognitive impairment and mild Alzheimer ’s disease . Larger , more controlled trials are needed to replicate and extend these findings ABSTRACT Objectives : Deficits in working memory ( WM ) are associated with age-related decline . We report findings from a clinical trial that examined the effectiveness of Cogmed , a computerized program that trains WM . We compare this program to a Sham condition in older adults with Mild Cognitive Impairment ( MCI ) . Methods : Older adults ( N = 68 ) living in the community were assessed . Participants reported memory impairment and met criteria for MCI , either by poor delayed memory or poor performance in other cognitive areas . The Repeatable Battery for the Assessment of Neuropsychological Status ( RBANS , Delayed Memory Index ) and the Clinical Dementia Rating scale ( CDR ) were utilized . All presented with normal Mini Mental State Exams ( MMSE ) and activities of daily living ( ADLs ) . Participants were r and omized to Cogmed or a Sham computer program . Twenty-five sessions were completed over five to seven weeks . Pre , post , and follow-up measures included a battery of cognitive measures ( three WM tests ) , a subjective memory scale , and a functional measure . Results : Both intervention groups improved over time . Cogmed significantly outperformed Sham on Span Board and exceeded in subjective memory reports at follow-up as assessed by the Cognitive Failures Question naire ( CFQ ) . The Cogmed group demonstrated better performance on the Functional Activities Question naire ( FAQ ) , a measure of adjustment and far transfer , at follow-up . Both groups , especially Cogmed , enjoyed the intervention . Conclusions : Results suggest that WM was enhanced in both groups of older adults with MCI . Cogmed was better on one core WM measure and had higher ratings of satisfaction . The Sham condition declined on adjustment ABSTRACT Cognitive rehabilitation for mild cognitive impairment ( MCI ) and early Alzheimer 's disease is readily available to the geriatric population . Initial evidence suggests that techniques incorporating motivational strategies to enhance treatment engagement may provide more benefit than computerised training alone . Seventy four adults with sub clinical cognitive decline were r and omly assigned to computerised cognitive training ( CCT ) , Cognitive Vitality Training ( CVT ) , or an Active Control Group ( ACG ) , and underwent neuropsychological evaluations at baseline and four-month follow-up . Significant differences were found in changes in performance on the Modified Mini Mental State Examination ( mMMSE ) and measures of verbal learning and memory across treatment groups . Experimental groups showed greater preservation of functioning on the mMMSE than the ACG group , the CVT group performed better than the ACG group on one measure of verbal learning and both measures of verbal memory , and the CCT group performed better than the ACG group on one measure of verbal learning and one measure of verbal memory . There were no significant group differences between the CVT and CCT groups on measures of verbal learning or memory . It was concluded that computerised cognitive training may offer the most benefit when incorporated into a therapeutic milieu rather than administered alone , although both appear superior to more generic forms of cognitive stimulation We performed a pilot r and omized , controlled trial of intensive , computer-based cognitive training in 47 subjects with mild cognitive impairment . The intervention group performed exercises specifically design ed to improve auditory processing speed and accuracy for 100 min/d , 5 d/wk for 6 weeks ; the control group performed more passive computer activities ( reading , listening , visuospatial game ) for similar amounts of time . Subjects had a mean age of 74 years and 60 % were men ; 77 % successfully completed training . On our primary outcome , Repeatable Battery for Assessment of Neuropsychological Status total scores improved 0.36 st and ard deviations ( SD ) in the intervention group ( P=0.097 ) compared with 0.03 SD in the control group ( P=0.88 ) for a nonsignificant difference between the groups of 0.33 SD ( P=0.26 ) . On 12 secondary outcome measures , most differences between the groups were not statistically significant . However , we observed a pattern in which effect sizes for verbal learning and memory measures tended to favor the intervention group whereas effect sizes for language and visuospatial function measures tended to favor the control group , which raises the possibility that these training programs may have domain-specific effects . We conclude that intensive , computer-based mental activity is feasible in subjects with mild cognitive impairment and that larger trials are warranted A r and omized pilot experiment examined the neural substrates of response to cognitive training in participants with mild cognitive impairment ( MCI ) . Participants performed exercises previously demonstrated to improve verbal memory and an active control group performed other computer activities . An auditory-verbal fMRI task was conducted before and after the two-month training program . Verbal memory scores improved significantly and left hippocampal activation increased significantly in the experimental group ( gains in 5 of 6 participants ) relative to the control group ( reductions in all 6 participants ) . Results suggest that the hippocampus in MCI may retain sufficient neuroplasticity to benefit from cognitive training Objective : To investigate the 10-year risk of dementia in subjects with mild cognitive impairment ( MCI ) ages 40 to 85 years . Methods : We selected subjects from a memory clinic if they met one of the following definitions of MCI : cognitive complaints ( n = 181 ) , aging-associated cognitive decline ( AACD ) ( n = 163 ) , mild functional impairment ( n = 86 ) , or amnestic MCI ( n = 64 ) . Subjects were reassessed after 2 , 5 , and 10 years . The risk of dementia was calculated with Kaplan-Meier statistics . Analyses were conducted in the entire sample and in subgroups of subjects aged 40 to 54 years , 55 to 69 years , and 70 to 85 years . Results : The 10-year risk of dementia was 0.27 ( 95 % CI 0.20 to 0.34 ) in subjects with cognitive complaints , 0.28 ( 95 % CI 0.21 to 0.35 ) in subjects with AACD , 0.44 ( 95 % CI 0.32 to 0.56 ) in subjects with mild functional impairment , and 0.48 ( 95 % CI 0.35 to 0.61 ) in subjects with amnestic MCI . Ninety-one percent of the demented subjects had probable AD . The risk of dementia increased with increasing age for all MCI definitions ( p < 0.001 ) . Depending on the MCI definition used , the risk for dementia ranged from 0 to 0.06 in subjects aged 40 to 54 years , from 0.37 to 0.52 in subjects aged 55 to 69 years , and from 0.77 to 1.0 in subjects aged 70 to 85 years . Conclusions : The majority of subjects with MCI do not progress to dementia at the long term . Age strongly influences the dementia risk . MCI often represents the predementia stage of a neurodegenerative disorder in elderly subjects but rarely in younger subjects This study evaluated the efficacy of a cognitive intervention for attentional control in older adults with mild cognitive impairment ( MCI ) with an executive deficit . It also sought to verify if the benefits of training generalised to primary and secondary outcome measures . Participants ( n = 24 ) were r and omly assigned to a training programme or active control condition . The experimental group completed a computer-based training programme involving Variable Priority ( VP ) coordination of both components of a dual task , to which was added a self-regulatory strategy design ed to augment meta-cognition . The active control group performed Fixed Priority ( FP ) training : rote practice of the same dual task involving a visual detection task combined with an alpha-arithmetic task . Six one-hour training sessions were held three times a week for two weeks . Participants were tested pre- and post-training to detect improvement and transfer effects . Both groups improved on the visual detection and alpha-arithmetic tasks completed in focused attention , but only participants receiving VP training significantly improved their dual-task cost in accuracy for the visual detection task . As for transfer effects , both FP and VP training produced improvements on select outcome measures : focused attention , speed of processing , and switching abilities . No reliable advantage for generalisability of VP over FP training was found . Overall , these findings indicate that cognitive intervention may improve attentional control in persons with MCI and an executive deficit BACKGROUND Mild cognitive impairment ( MCI ) increases dementia risk with no pharmacologic treatment available . METHODS The Study of Mental and Resistance Training was a r and omized , double-blind , double-sham controlled trial of adults with MCI . Participants were r and omized to 2 supervised interventions : active or sham physical training ( high intensity progressive resistance training vs seated calisthenics ) plus active or sham cognitive training ( computerized , multidomain cognitive training vs watching videos/quizzes ) , 2 - 3 days/week for 6 months with 18-month follow-up . Primary outcomes were global cognitive function ( Alzheimer 's Disease Assessment Scale-cognitive subscale ; ADAS-Cog ) and functional independence ( Bayer Activities of Daily Living ) . Secondary outcomes included executive function , memory , and speed/attention tests , and cognitive domain scores . RESULTS One hundred adults with MCI [ 70.1 ( 6.7 ) years ; 68 % women ] were enrolled and analyzed . Resistance training significantly improved the primary outcome ADAS-Cog ; [ relative effect size ( 95 % confidence interval ) -0.33 ( -0.73 , 0. Output:	Some cognitive interventions improved non-cognitive symptoms such as anxiety , depression , and ADLs .
MS21308	*TASK* the task is to summarize an input biomedical literature in six sentences *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 series of 100 consecutive patients with unstable intertrochanteric fractures were treated by compression hip screw fixation ; 55 patients had an anatomical reduction ( Group 1 ) and 45 patients a Sarmiento osteotomy and valgus reduction ( Group 2 ) . Group 1 spent an average of 10 days less in hospital than Group 2 ( 21 days compared with 31 days ) ( P less than 0.02 ) . They also had a greater chance of returning to their pre-injury accommodation and of achieving their pre-injury walking capability . Radiological failure of fracture fixation , with varus angulation of the femoral head by cutting out of the screw , was seen seven times in Group 1 but only once in Group 2 . Anatomical reduction provides better clinical results than valgus osteotomy in the patient with an unstable intertrochanteric fracture stabilized by a compression hip screw . The capacity for failure of fracture fixation is greater , however , in the former . Valgus osteotomy provides a simple means of securing a stable reduction of the fracture which can not be satisfactorily reduced by closed means Osteotomy has been used in the treatment of unstable intertrochanteric hip fractures in an attempt to increase the stability of the fracture fragments . We have assessed this stability in a r and omised prospect i ve trial on 100 consecutive patients , all having fixation by an AO dynamic hip screw , comparing anatomical reduction with two types of osteotomy . The groups were similar in terms of age , gender , mental test score , and fracture configuration . There were more failures of fixation in the osteotomy groups , and the operations took longer . We found no clear benefit from osteotomy and therefore recommend anatomical reduction and fixation by a sliding hip screw in most cases . Rarely , a fracture configuration which does not allow load-sharing between the fracture fragments and the device may benefit from an osteotomy or the use of an alternative implant Objective This study evaluates the safety and outcome of a minimally invasive technique for inserting a st and ard dynamic hip screw for intertrochanteric fractures . Hypothesis The use of st and ard plate in a minimally invasive technique is both possible and advantageous to patient outcome . Design and Methods Prospect i ve surgeon-r and omized blinded outcome clinical study comparing new technique to conventional technique . Main Outcome Measure Pain , operative time and mean hemoglobin drop in percutaneous hip fixation . Results The minimally invasive technique had significantly less blood loss ( P < 0.001 ) , operative time ( P < 0.001 ) and a trend to less morphine use . Conclusions Minimal invasive technique significantly reduces blood loss and operative time for fixation of intertrochanteric hip fractures without sacrifice of fixation stability or bone healing The triple reamer is a convenient tool for reaming the proximal femur when using a sliding screw and plate device , but unnecessarily high temperatures may be generated within the femoral head while the lateral cortex is being reamed . Nineteen female patients over 60 years old were r and omized to either the st and ard or a modified reaming technique with the triple reamer during internal fixation of proximal femoral fractures . Temperatures generated within the femoral head were measured . Results showed a mean peak temperature of 51.9 degrees C ( range 42 - 66 ) using the st and ard method and 46.3 degrees C ( range 40 - 52 ) using the modified method ( P = 0.07 ) . A significant difference ( P < 0.05 ) was found in the duration of temperature elevation above the critical 44 degrees C ( 17.4s vs 5.7s ) , it being prolonged in the st and ard group . Even in this osteoporotic patient group , damaging temperatures which may contribute to the mechanical failure of fixation , are generated within the femoral head . A simple method to avoid this problem is described We undertook a multicentre , prospect i ve study of a series of 112 unstable trochanteric fractures in order to evaluate if internal fixation with a sliding screw device combined with augmentation using a calcium phosphate degradable cement ( Norian SRS ) could improve the clinical , functional and radiological outcome when compared with fractures treated with a sliding screw device alone . Pain , activities of daily living , health status ( SF-36 ) , the strength of the hip abductor muscles and radiological outcome were analysed . Six weeks after surgery , the patients in the augmented group had significantly lower global and functional pain scores ( p < 0.003 ) , less pain after walking 50 feet ( p < 0.01 ) , and a better return to the activities of daily living ( p < 0.05 ) . At follow-up at six weeks and six months , those in the augmented group showed a significant improvement compared with the control group in the SF-36 score . No other significant differences were found between the groups . We conclude that augmentation with calcium phosphate cement in unstable trochanteric fractures provides a modest reduction in pain and a slight improvement in the quality of life during the course of healing when compared with conventional fixation with a sliding screw device alone We report a prospect i ve clinical trial of 150 cases for the treatment of unstable intertrochanteric fracture of the neck of the femur . Three methods were tested in our series -- skeletal traction with a tibial pin , medial displacement osteotomy and valgus osteotomy -- with 50 patients in each group . Our results showed no significant difference between those treated with the Dimon and Hughston osteotomy and those treated by the Sarmiento osteotomy . Conservative treatment of skeletal traction for unstable fracture was found to be well tolerated by the Chinese patient . A low mortality and morbidity rate was found in this series with an overall infection rate of 4 per cent 153 patients with a trochanteric hip fracture were operated on with a compression hip screw ( CHS ) and followed for 4 months . They were r and omized into 2 groups , with or without a key and compression of the lag screw . Greater sliding of the lag screw was noted in cases where the compression screw and the key were used , especially in women over 80 years of age and in patients with a previous fracture indicating osteoporotic bone . Use of a key and compression of the lag screw gave no advantage , and we do not recommend this for treatment of trochanteric hip fractures This study was done to determine if elderly patients with trochanteric fractures and with osteoporosis could benefit from treatment with a dynamic hip screw fixed with HA-coated AO/ASIF screws . One hundred twenty patients with AO , A1 , or A2 trochanteric fractures were selected . Patients were divided into two groups and r and omized to receive a 135 ° -four – hole dynamic hip screw fixed with either st and ard lag and cortical AO/ASIF screws ( Group A ) , or HA-coated lag and cortical AO/ASIF screws ( Group B ) . Lag screw cutout occurred in four patients in Group A , but not in any patients in Group B. In Group A , the femoral neck shaft angle was 134 ° ± 5 ° postoperatively and 127 ° ± 12 ° at 6 months . In Group B , the femoral neck shaft angle was 134 ° ± 7 ° postoperatively and 133 ° ± 7 ° at 6 months . The Harris hip score at 6 months was 60 ± 25 in Group A and 71 ± 18 in Group B. The superior results of Group B can be attributed to the increased screw fixation provided by the HA-coated screws . We recommend lag screws coated with HA for dynamic hip screw fixation , especially in osteoporotic bone Sliding hip screws have improved the treatment of unstable intertrochanteric hip fractures and their success , compared with fixed devices , is in large part due to the sharing of load between the implant and the fracture fragments . In a prospect i ve study of 100 patients with such fractures , five factors concerned with the fracture and its fixation were studied and odds ratios calculated of their relative importance in prediction of failure . The most important factor affecting the load borne by the fracture fragments was the amount of slide available within the device , and that affecting the load carried by the device was the position of the screw in the femoral head . For fractures fixed with a device allowing less than 10 mm of slide , and those with superior screw position , the risk of failure was increased by factors of 3.2 and 5.9 , respectively . Anatomical reduction alone , rather than osteotomy , together with sliding hip screw fixation , has been recommended for these fractures in three prospect i ve r and omized trials . It is calculated here that to allow sufficient slide when employing this technique , it is essential to use a short barrel device when using dynamic screws of 85 mm or less . This has not been demonstrated before We conducted a prospect i ve r and omised trial to compare the results of anatomical reduction and medial displacement osteotomy in 127 consecutive patients with unstable intertrochanteric fractures , of whom 109 completed the study . After an average follow-up of 11 months , we found no significant differences in walking ability , social status or failure of fixation in the two groups . Postoperative complication rates and the early mortality rate were not significantly different , but operating time and blood loss were significantly higher in the osteotomy group . With the use of modern sliding hip screws , medial displacement osteotomy is rarely indicated for unstable intertrochanteric fractures A total of 62 patients with unstable pertrochanteric fractures of the neck of the femur was subjected to either nail plating with 130 degrees neck-shaft angle or valgus osteotomy using a neck-shaft angle of at least 140 degrees . The patients were assessed in terms of ability to walk and stability of fracture fixation . A clear superiority of valgus osteotomy over the controls was demonstrated in terms of fracture fixation , but the difference in terms of ability to walk was less remarkable BACKGROUND Animal studies have demonstrated the efficacy of the use of bisphosphonates to enhance screw fixation in bone . In this prospect i ve , r and omized study of pertrochanteric fractures treated with external fixation , we tested whether systemic administration of bisphosphonates would improve the fixation of hydroxyapatite-coated screws implanted in osteoporotic bone . METHODS Sixteen consecutive patients with a pertrochanteric fracture were selected . Inclusion criteria were female gender , an age of at least sixty-five years , and a bone mineral density T-score of less than -2.5 st and ard deviations . Exclusion criteria included bisphosphonate treatment during the two-year period prior to the fracture . Fractures were fixed with a pertrochanteric fixator and four hydroxyapatite-coated pins . Two pins were implanted in the femoral head ( pin positions 1 and 2 ) , and two were placed in the femoral diaphysis ( pin positions 3 and 4 ) . The patients were r and omized either to therapy with alendronate for a three-month postoperative period ( Group A ) or to no therapy ( Group B ) . The Group-A patients received an oral dose of 70 mg of alendronate per week . The fixators were removed after three months . RESULTS All of the fractures healed , and no loss of reduction , nonunion , or delayed union was observed . The combined mean extraction torque ( and st and ard deviation ) of the pins implanted at positions 1 and 2 ( cancellous bone ) was 2558 + /- 1103 N/mm in Group A and 1171 + /- 480 N/mm in Group B ( p < 0.0005 ) . The combined mean extraction torque of the pins implanted at positions 3 and 4 ( cortical bone ) was 4327 + /- 1720 N/mm in Group A and 4075 + /- 1022 N/mm in Group B. CONCLUSIONS These data show that weekly systemic administration of alendronate improves pin fixation in cancellous bone in elderly female patients with osteoporosis . We observed a twofold increase in extraction torque with the pins implanted in cancellous bone . These results support the use of alendronate in the treatment of osteoporotic pertrochanteric fractures to improve screw fixation in the femoral head Output:	Osteotomy was associated with an increased operative blood loss and length of surgery . There were no statistically significant differences for mortality , morbidity or measures of anatomical deformity . The cement group had significantly better quality of life scores at six months . There is inadequate evidence to support the use of osteotomy for internal fixation of a trochanteric hip fracture . Similarly , there is insufficient evidence to support the use of the other techniques examined in the trials included in this review
MS21309	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Throughout the literature , drug-related problems ( DRPs ) , such as medication reconciliation issues and potentially inappropriate prescribing , have been reported to be associated with adverse outcomes in older individuals . Both structured pharmacist review of medication ( SPRM ) interventions and computerized decision support systems ( CDSSs ) have been shown to reduce DRPs . Objective The objectives of this study were to ( i ) evaluate the impact of a specially developed SPRM/CDSS intervention on the appropriateness of prescribing in older Irish hospital in patients , and ( ii ) examine the acceptance rates of these recommendations . Methods We prospect ively review ed 361 patients , aged ≥65 years who were admitted to an Irish university teaching hospital over a 12-month period . At the point of admission , the patients received a SPRM/CDSS intervention , which screened for DRPs . Any DRPs that were identified were then communicated in writing to the attending medical team . The patient ’s medical records were review ed again at 7–10 days , or at the point of discharge ( whichever came first ) . Results Of the 361 patients review ed , 181 ( 50.1 % ) were female ; the median age was 77 years [ interquartile range ( IQR ) 71–83 years ) . A total of 3,163 ( median 9 , IQR 6–12 ) and 4,192 ( median 12 , IQR 8–15 ) medications were prescribed at admission and discharge , respectively . The SPRM generated 1,000 recommendations in 296 patients . Of the 1,000 recommendations , 548 ( 54.8 % ) were implemented by the medical teams accordingly . The SPRM/CDSS intervention result ed in an improvement in the appropriateness of prescribing as defined by the medication appropriateness index ( MAI ) , with a statistically significant difference in the median summated MAI at admission ( 15 , IQR : 7–21 ) and follow-up ( 12 , IQR : 6–18 ) ; p < 0.001 . However , the SPRM did not result in an improvement in appropriateness of underprescribing as defined by a modified set assessment of care of vulnerable elders ( ACOVE ) criteria . Conclusion This study indicated that DRPs are prevalent in older Irish hospitalized in patients and that a specially developed SPRM intervention supported by a CDSS can improve both the appropriateness and accuracy of medication regimens of older hospitalized in patients BACKGROUND Falls are the leading cause of both fatal and nonfatal injuries among older adults in the United States . Medications that affect the central nervous system are known to increase the risk of falling . OBJECTIVE The purpose of this study was to assess the effects of a community pharmacy-based falls-prevention program targeting high-risk older adults on the rates of recurrent falls , injurious falls , and filling prescriptions for medications that have been associated with an increased risk of falling . METHODS This was a r and omized controlled trial of participants recruited through a community pharmacy chain in North Carolina . The 2-year study consisted of a 1-year " look-back " period before r and omization and a 1-year follow-up period after r and omization . Patients were eligible to participate if they were ≥65 years of age , had fallen at least once during the 1-year period preceding enrollment , and were taking medications associated with an increased risk of falling . Medications classified as high risk included benzodiazepines , antidepressants , anticonvulsants , sedative hypnotics , opioid analgesics , antipsychotics , and skeletal muscle relaxants . Participants were assigned to either the intervention arm or the control arm ; participants in the intervention arm were invited to attend a face-to-face medication consultation conducted by a community pharmacy resident , whereas those in the control arm received no medication consultation . The primary end point was the rate of recurrent falls during the 1-year followup period . Secondary end points were the total number of prescriptions for high-risk medications filled during the follow-up period and either discontinued use or a reduction in the dosage of a high-risk medication during the follow-up period . RESULTS One hundred eighty-six patients ( 132 women , 54 men ; 88.7 % white ) were enrolled . Intention-to-treat ( ITT ) analyses revealed no significant differences in the rates of recurrent falls , injurious falls , or filling prescriptions for high-risk medications . However , 13 patients in the intervention group either discontinued use of a high-risk medication or had the dosage reduced during the follow-up period , compared with 5 patients in the control group ( χ(2 ) = 3.94 ; P < 0.05 ) . As-treated analyses revealed numeric reductions in the rates of falls ( rate ratio [ RR ] = 0.76 ; 95 % CI , 0.53 - 1.09 ) , injurious falls ( RR= 0.67 ; 95 % CI , 0.43 - 1.05 ) , and filling prescriptions for high-risk medications ( RR= 0.85 ; 95 % CI , 0.72 - 1.03 ) after receipt of the intervention , but the differences were not statistically significant . CONCLUSIONS Results of this study support the feasibility of using community pharmacies to deliver a falls-prevention program targeting high-risk older adults . Although the ITT analyses revealed no significant reduction in the rate of recurrent falls , injurious falls , or overall use of high-risk medications , individuals in the intervention group were more likely than those in the control group to discontinue use of a high-risk medication or have the dosage reduced during the 1-year follow-up period . More work is needed to evaluate the intervention using a larger sample size that provides greater power to detect clinical ly meaningful effects of reduction in the use of high-risk medications on preventing or reducing falls in the high-risk population OBJECTIVES to investigate the effectiveness of a pharmacy discharge plan in elderly hospitalized patients . DESIGN r and omized controlled trial . SUBJECTS AND SETTING S we r and omized patients aged 75 years and older on four or more medicines who had been discharged from three acute general and one long-stay hospital to a pharmacy intervention or usual care . INTERVENTIONS the hospital pharmacist developed discharge plans which gave details of medication and support required by the patient . A copy was given to the patient and to all relevant professionals and carers . This was followed by a domiciliary assessment by a community pharmacist . In the control group , patients were discharged from hospital following st and ard procedures that included a discharge letter to the general practitioner listing current medications . OUTCOMES the primary outcome was re-admission to hospital within 6 months . Secondary outcomes included the number of deaths , attendance at hospital outpatient clinics and general practice and proportion of days in hospital over the follow-up period , together with patients ' general well-being , satisfaction with the service and knowledge of and adherence to prescribed medication . RESULTS we recruited 362 patients , of whom 181 were r and omized to each group . We collected hospital and general practice data on at least 91 and 72 % of patients respectively at each follow-up point and interviewed between 43 and 90 % of the study subjects . There were no significant differences between the groups in the proportion of patients re-admitted to hospital between baseline and 3 months or 3 and 6 months . There were no significant differences in any of the secondary outcomes . CONCLUSIONS we found no evidence to suggest that the co-ordinated hospital and community pharmacy care discharge plans in elderly patients in this study influence outcomes OBJECTIVES To evaluate the effect of pharmaceutical care provided in addition to acute Geriatric Evaluation and Management ( GEM ) care on the appropriateness of prescribing . DESIGN R and omized , controlled trial , with the patient as unit of r and omization . SETTING Acute GEM unit . PARTICIPANTS Two hundred three patients aged 70 and older . INTERVENTION Pharmaceutical care provided from admission to discharge by a specialist clinical pharmacist who had direct contacts with the GEM team and patients . MEASUREMENTS Appropriateness of prescribing on admission , at discharge , and 3 months after discharge , using the Medication Appropriateness Index ( MAI ) , Beers criteria , and Assessing Care of Vulnerable Elders ( ACOVE ) underuse criteria and mortality , readmission , and emergency visits up to 12 months after discharge . RESULTS Intervention patients were significantly more likely than control patients to have an improvement in the MAI and in the ACOVE underuse criteria from admission to discharge ( odds ratio (OR)=9.1 , 95 % confidence interval (CI)=4.2 - 21.6 and OR=6.1 , 95 % CI=2.2 - 17.0 , respectively ) . The control and intervention groups had comparable improvements in the Beers criteria . CONCLUSION Pharmaceutical care provided in the context of acute GEM care improved the appropriate use of medicines during the hospital stay and after discharge . This is an important finding , because only limited data exist on the effect of various strategies to improve medication use in elderly in patients . The present approach has the potential to minimize risk and improve patient outcomes Objective To examine the prevalence of outcome reporting bias — the selection for publication of a subset of the original recorded outcome variables on the basis of the results — and its impact on Cochrane review s. Design A nine point classification system for missing outcome data in r and omised trials was developed and applied to the trials assessed in a large , unselected cohort of Cochrane systematic review s. Research ers who conducted the trials were contacted and the reason sought for the non-reporting of data . A sensitivity analysis was undertaken to assess the impact of outcome reporting bias on review s that included a single meta- analysis of the review primary outcome . Results More than half ( 157/283 ( 55 % ) ) the review s did not include full data for the review primary outcome of interest from all eligible trials . The median amount of review outcome data missing for any reason was 10 % , whereas 50 % or more of the potential data were missing in 70 ( 25 % ) review s. It was clear from the publications for 155 ( 6 % ) of the 2486 assessable trials that the research ers had measured and analysed the review primary outcome but did not report or only partially reported the results . For reports that did not mention the review primary outcome , our classification regarding the presence of outcome reporting bias was shown to have a sensitivity of 88 % ( 95 % CI 65 % to 100 % ) and specificity of 80 % ( 95 % CI 69 % to 90 % ) on the basis of responses from 62 trialists . A third of Cochrane review s ( 96/283 ( 34 % ) ) contained at least one trial with high suspicion of outcome reporting bias for the review primary outcome . In a sensitivity analysis undertaken for 81 review s with a single meta- analysis of the primary outcome of interest , the treatment effect estimate was reduced by 20 % or more in 19 ( 23 % ) . Of the 42 meta-analyses with a statistically significant result only , eight ( 19 % ) became non-significant after adjustment for outcome reporting bias and 11 ( 26 % ) would have overestimated the treatment effect by 20 % or more . Conclusions Outcome reporting bias is an under-recognised problem that affects the conclusions in a substantial proportion of Cochrane review s. Individuals conducting systematic review s need to address explicitly the issue of missing outcome data for their review to be considered a reliable source of evidence . Extra care is required during data extraction , review ers should identify when a trial reports that an outcome was measured but no results were reported or events observed , and contact with trialists should be encouraged Aim : To measure the outcomes of a harmonised , structured pharmaceutical care programme provided to elderly patients by community pharmacists . Method : A r and omised , controlled , longitudinal , clinical trial with repeated measures was performed over an 18‐month period , involving community pharmacies ( 5 intervention and 5 control ) in Northern Irel and . Elderly , ambulatory patients ( ≥ 65 years ) , taking 4 or more prescribed medications were eligible for participation . Patients attending an intervention pharmacy received education on medical conditions , implementation of compliance strategies , rationalising of drug regimens and appropriate monitoring ; patients attending control sites received normal services . A battery of clinical , humanistic and economic outcomes were assessed . Results : A significantly higher proportion of intervention patients were compliant at the end of the 18‐month study and experienced fewer problems with medication compared to control patients ( P < 0.05 ) . There was little impact on quality of life and health care utilisation . Conclusions : Pharmaceutical care provision to community‐dwelling patients result ed in an improvement in medication compliance and evidence of cost‐savings . Future pharmaceutical care studies may benefit from a more focussed selective approach to data collection and outcomes measurement OBJECTIVES to evaluate specialist geriatric input and medication review in patients in high-dependency continuing care . DESIGN prospect i ve , r and omised , controlled trial . SETTING two residential continuing care hospitals . PARTICIPANTS two hundred and twenty-five permanent patients . INTERVENTION patients were r and omised to either specialist geriatric input or regular input . The specialist group had a medical assessment by a geriatrician and medication review by a multidisciplinary expert panel . Regular input consisted of review as required by a medical officer attached to each ward . Re assessment occurred after 6 months . RESULTS one hundred and ten patients were r and omised to specialist input and 115 to regular input . These were comparable for age , gender , dependency levels and cognition . After 6 months , the total number of medications per patient per day fell from 11.64 to 11.09 in the specialist group ( P = Output:	Conclusion Outcome reporting from RCTs concerning medication review in older patients is heterogeneous .
MS21310	*TASK* the task is to summarize an input biomedical literature in six sentences *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 We aim ed to reduce unnecessary prostatic biopsy in patients with high prostate-specific antigen ( PSA ) by consideration of prostatic inflammation . Material s and Methods The investigation was conducted prospect ively in 413 patients with a PSA level of 4 to 10 ng/ml from January 2004 to December 2009 . All patients underwent the expressed prostatic secretion ( EPS ) or voided bladder urine 3 ( VB3 ) test to be classified into two groups : positive group and negative group . Patients with a positive result on the EPS or VB3 test were treated with antibiotics for 2 months , and in cases in which the PSA level remained high , we performed prostate biopsy . In patients with a negative result on the VB3 test , we performed prostate biopsy directly . Results Of the 413 study patients , 215 ( 52 % ) patients had positive findings on the EPS or VB3 test . After 8 weeks of antibiotics therapy , 53 of the 215 men avoided prostate biopsy because their PSA level was normalized . The other patients ( 162 of 215 ) still had elevated PSA levels of more than 4 ng/ml , including 7 patients in whom the biopsy revealed cancer . Patients with negative findings ( 198 of 413 ) underwent prostate biopsy . Of the 198 patients , 41 were diagnosed with prostate cancer . The total prostate cancer detection rate was 11.6 % in our subjects , where as it was 20.7 % in the patients with negative findings on the EPS or VB3 and 3.3 % in the patients with positive findings , respectively . Conclusions In cases in which the PSA level is increasing , if we first exclude prostatitis and carry out a serial diagnostic procedure , it may help to reduce unnecessary prostatic biopsy Purpose We investigated the effect of antibiotics on PSA in asymptomatic patients with mild PSA elevation . Material s and Methods We prospect ively evaluated , in a non-r and omized design , 106 asymptomatic patients with PSA of 4 - 10ng/mL , with a negative digital rectal examination and with no urinary tract infection evidence for 2 years . Patients were divided into two groups : those treated with antibiotics for 3 weeks ( G1 ) and those who were not treated ( G2 ) . PSA was taken six weeks after and prostate biopsy was performed in all patients . Results PCa was diagnosed in 25 of 106 patients ( 23.6 % ) : 16 ( 25.0 % ) in G1 and 9 ( 21.4 % ) in G2 ( p>0.05 ) . PSA normalization was experienced in 24.5 % . In G1 , PSA returned to < 4ng/mL in 15 ( 23.4 % ) patients compared to 11 ( 26 % ) patients in G2 . In the patients with a positive biopsy , no significant variation was noted in PSA , fPSA , % fPSA and DPSA after antibiotic treatment . A significantly lower cancer detection rate was noted with decreased PSA , fPSA , and DPSA after antibiotic use . A PSA reduction rate of ≥10 % occurred in 58.5 % , and this was similar in both G1 and G2 groups . The sensibility , specificity and accuracy of PSA reduction of ≥10 % were 31 % , 23 % and 25 % , respectively . Conclusion Empirical antibiotic therapy in asymptomatic male patients is not related to PSA reduction . The greater than 10 % PSA reduction after antibiotic in this population can not postpone prostate biopsy PURPOSE This controlled prospect i ve study aims to investigate the possible effects of antibiotic treatment on prostate-specific antigen ( PSA ) and its derivatives , and consequently on the transrectal biopsy rates , in the diagnosis of prostate cancer . PATIENTS AND METHODS One hundred and forty patients aged 45 to 70 years old , with a PSA level between 2.5 and 10 ng/mL and normal digital rectal examinations ( DRE ) , were included in this study between June 2009 and November 2010 . The patients were r and omly assigned into two groups . The first group received oral levofloxacin 500 mg 1 * 1 for 21 days ; the second , the control group , was given no treatment . Initially , total PSA , free PSA , a DRE , urinary ultrasonography ( including prostate volume , postvoiding residual urine ) , uroflowmetry , International Prostate Symptom Score , National Institutes of Health Chronic Prostatitis Symptom Index , and International Index of Erectile Function tests were performed . All of these were repeated at the end of 3 weeks of antibiotic treatment . An additional PSA measurement was also performed at day 10 of the treatment . All patients underwent transrectal ultrasonography ( TRUS ) guided prostate biopsy at day 21 , just the day after the final ( third ) PSA sampling . RESULTS The mean age of the patients was 59.6 years . Overall , in 23 patients , prostate cancer was detected , including those found in the rebiopsies . Statistically , there were significant changes in values of PSA and its derivatives in the treatment group ( from 5.31 to 4.69 and 4.58 ng/mL , consecutively ) . Focusing on prostate cancer patients in both the treatment and control groups , however , we did not detect any significant change in the same parameters . CONCLUSION Antibiotic treatment given to the patients with a PSA level between 2.5 and 10 ng/mL can be beneficial , before a decision for TRUS guided prostate biopsy , just in a limited subgroup , by reducing the PSA levels below the threshold value . Considering the large population of patients in the gray zone , however , it still does not provide clear solid evidence for avoiding unnecessary prostate biopsies INTRODUCTION We investigated if antibiotherapy has any role on total PSA ( tPSA ) , free PSA ( fPSA ) and fPSA/tPSA ratio in patients with tPSA higher than 2.5ng/ml . We also analyzed if it has any relation with prostate cancer diagnosis rate . MATERIAL AND METHODS A total 108 patients older than 50 years of age with lower urinary system sypmtoms and tPSA > 2.5ng/ml were included in this study . Antibiotherapy was given to all the cases for three weeks . After that , transrectal ultrasound-guided prostate biopsies were taken from all the patients . Before and after antibiotherapy , " The International Prostate Symptom Score " ( IPSS ) and " National Institutes of Health Chronic Prostatitis Symptom Index " ( NIH-CPSI ) questinories are performed and serum tPSA , fPSA and fPSA/tPSA values were obtained . RESULTS TPSA , fPSA and fPSA/tPSA ratio alterations prior to and after antibiotherapy did not show any statistically significant difference ( p>0.05 ) . When prostate adenocarcinoma was excluded , an statistically significant decrease was found in IPSS and NIH-CPSI scores for all cases . CONCLUSIONS Antibiotherapy given to patients with PSA levels higher than threshold value has not led to significant change in prostate needle biopsy decision . Prostate biopsy should be considered without trying antibiotherapy in patients with high PSA values if a suspicion of prostatitis does not exist PURPOSE We compared baseline and post-therapy prostate specific antigen ( PSA ) in patients with chronic bacterial prostatitis who were treated with levofloxacin or ciprofloxacin . MATERIAL S AND METHODS Subset analysis was done using a r and omized , multicenter , double-blind , active control trial of 500 mg levofloxacin daily for 28 days vs 500 mg ciprofloxacin twice daily in 28 days in men with chronic bacterial prostatitis . RESULTS Of the 377 men in the intent to treat population , including 197 treated with levofloxacin and 180 treated with ciprofloxacin , 35 on levofloxacin and 37 on ciprofloxacin with baseline PSA greater than 4 ng/ml were included in this analysis . Excluded from analysis were 2 levofloxacin treated patients with extremely high PSA at baseline ( 62 and 103 ng/ml , respectively ) . Mean baseline PSA + /- SD in the patients analyzed was 8.33 + /- 4.46 ng/ml , which decreased to 5.36 + /- 3.82 ng/ml after therapy . There was no significant difference in the mean change in PSA between the levofloxacin and ciprofloxacin groups . Approximately 42 % of patients with increased baseline PSA had a post-therapy PSA of 4 ng/ml or less . Of patients who were microbiologically evaluable and had normalized PSA after therapy levofloxacin eradicated the pathogen in 90.9 % ( 10 of 11 ) . However , of patients in whom post-therapy PSA remained increased the microbiological eradication rate was 69.2 % ( 9 of 13 ) . Similarly 93.3 % of the ciprofloxacin group ( 14 of 15 patients ) with normalized post-therapy PSA experienced microbiological eradication compared with 61.5 % ( 8 of 13 ) with continued increased PSA after therapy . CONCLUSIONS Approximately 20 % of patients diagnosed with chronic bacterial prostatitis had increased PSA . A significant decrease in PSA was observed in these patients after treatment with levofloxacin or ciprofloxacin . An association was observed between bacterial persistence and the likelihood that PSA would return to normal PURPOSE We attempted to identify morphological parameters of benign prostatic hyperplastic inflammation that correlate with pre-biopsy prostate specific antigen ( PSA ) concentrations . MATERIAL S AND METHODS Patients undergoing prostate biopsy at our department were prospect ively studied between January 1995 and January 1996 . preoperative blood and 24-hour urine sample s were measured for PSA . Biopsy sample s harboring exclusively benign prostatic tissue were grade d on a 4-point scale for inflammation ( 0-no inflammatory cells , 1-scattered inflammatory cell infiltrate , 2-nonconfluent lymphoid nodules and 3-large inflammatory areas with confluence of infiltrate ) and aggressiveness ( 0-no contact between inflammatory cells and gl and ular epithelium ; 1-contact between inflammatory cell infiltrate and gl and ular epithelium ; 2-clear but limited , that is less than 25 % of the examined material , gl and ular epithelium disruption , and 3-gl and ular epithelium disruption on more than 25 % of the examined material ) . RESULTS A total of 66 patients with exclusively benign prostatic tissue on prostate biopsies was analyzed . Difference between inflammation grade d groups was not significant when considering serum or urinary PSA . There was a significant correlation between aggressiveness grading and serum PSA ( rho = 0.51 , p < 0.0001 ) , whereas aggressiveness grading and urinary PSA did not correlate ( rho = -0.06 , p = 0.6 ) . CONCLUSIONS Prostatic sub clinical inflammation is not associated with high urinary PSA . Unless associated with gl and ular epithelial disruption , density of prostatic interstitial inflammatory cell infiltrate is not significantly correlated with serum PSA concentration . We believe that this issue should be considered when interpreting a prostate biopsy Purpose We evaluated men with documented chronic prostatitis and elevated serum prostate-specific antigen ( PSA ) to determine whether treatment with antibiotics and anti-inflammatory drugs can lower serum PSA and the cancer detection rate in patients with post-treatment PSA < 4 ng/ml . Material s and Methods Eighty-six men who presented with serum PSA greater than 4 ng/ml and who were subsequently diagnosed with chronic prostatitis with greater than 10 white blood cells per high power field in expressed prostatic excretions were included in this prospect i ve study . Patients meeting these criteria underwent treatment with a 4-week course of antibiotics and nonsteroidal anti-inflammatory agents . Follow-up PSA and transrectal ultrasonography-guided prostate biopsy were performed within 2 months of treatment for all patients . Results Mean patient age was 56.2 years ( range , 37 - 72 years ) . Mean PSA ( ng/ml ) decreased by 33.8 % , from 8.12 ( range , 4.02 - 24.8 ) to 5.37 ( range , 1.35 - 12.94 ) , after treatment ( p=0.001 ) . Pathological studies revealed prostate cancer in 18 cases ( 20.9 % ) , chronic inflammation in 64 ( 74.4 % ) , and benign prostatic hypertrophy in 4 ( 4.7 % ) . The prostate cancer detection rate according to the follow-up PSA level , below 2.5 , from 2.5 to 4.0 , and above 4.0 , was 13.3 % ( 2/15 ) , 13.6 % ( 3/22 ) , and 26.5 % ( 13/49 ) , respectively . Conclusions When chronic prostatitis with elevated PSA is identified , antibiotic and anti-inflammatory treatment can lower these PSA levels . However , the possibility of prostate Output:	No cancer was detected if the PSA level decreased to < 4 ng/mL. Conclusion : Antibiotic therapy is clinical ly beneficial in patients with high PSA levels . PSA reduction or normalisation after medical therapy , either antibiotic and /or NSAID , for ≥ 2 weeks can avoid unnecessary PBx .
MS21311	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Summary Background Although structured psychological treatments are recommended as first-line interventions for depression , only a small fraction of people globally receive these treatments because of poor access in routine primary care . We assessed the effectiveness and cost-effectiveness of a brief psychological treatment ( Healthy Activity Program [ HAP ] ) for delivery by lay counsellors to patients with moderately severe to severe depression in primary health-care setting s. Methods In this r and omised controlled trial , we recruited participants aged 18–65 years scoring more than 14 on the Patient Health Question naire 9 ( PHQ-9 ) indicating moderately severe to severe depression from ten primary health centres in Goa , India . Pregnant women or patients who needed urgent medical attention or were unable to communicate clearly were not eligible . Participants were r and omly allocated ( 1:1 ) to enhanced usual care ( EUC ) alone or EUC combined with HAP in r and omly sized blocks ( block size four to six [ two to four for men ] ) , stratified by primary health centre and sex , and allocation was concealed with use of sequential numbered opaque envelopes . Physicians providing EUC were masked . Primary outcomes were depression symptom severity on the Beck Depression Inventory version II and remission from depression ( PHQ-9 score of < 10 ) at 3 months in the intention-to-treat population , assessed by masked field research ers . Secondary outcomes were disability , days unable to work , behavioural activation , suicidal thoughts or attempts , intimate partner violence , and re source use and costs of illness . We assessed serious adverse events in the per- protocol population . This trial is registered with the IS RCT N registry , number IS RCT N95149997 . Findings Between Oct 28 , 2013 , and July 29 , 2015 , we enrolled and r and omly allocated 495 participants ( 247 [ 50 % ] to the EUC plus HAP group [ two of whom were subsequently excluded because of protocol violations ] and 248 [ 50 % ] to the EUC alone group ) , of whom 466 ( 95 % ) completed the 3 month primary outcome assessment ( 230 [ 49 % ] in the EUC plus HAP group and 236 [ 51 % ] in the EUC alone group ) . Participants in the EUC plus HAP group had significantly lower symptom severity ( Beck Depression Inventory version II in EUC plus HAP group 19·99 [ SD 15·70 ] vs 27·52 [ 13·26 ] in EUC alone group ; adjusted mean difference −7·57 [ 95 % CI −10·27 to −4·86 ] ; p<0·0001 ) and higher remission ( 147 [ 64 % ] of 230 had a PHQ-9 score of < 10 in the HAP plus EUC group vs 91 [ 39 % ] of 236 in the EUC alone group ; adjusted prevalence ratio 1·61 [ 1·34–1·93 ] ) than did those in the EUC alone group . EUC plus HAP showed better results than did EUC alone for the secondary outcomes of disability ( adjusted mean difference −2·73 [ –4·39 to −1·06 ] ; p=0·001 ) , days out of work ( −2·29 [ –3·84 to −0·73 ] ; p=0·004 ) , intimate partner physical violence in women ( 0·53 [ 0·29–0·96 ] ; p=0·04 ) , behavioural activation ( 2·17 [ 1·34–3·00 ] ; p<0·0001 ) , and suicidal thoughts or attempts ( 0·61 [ 0·45–0·83 ] ; p=0·001 ) . The incremental cost per quality -adjusted life-year gained was $ 9333 ( 95 % CI 3862–28 169 ; 2015 international dollars ) , with an 87 % chance of being cost-effective in the study setting . Serious adverse events were infrequent and similar between groups ( nine [ 4 % ] in the EUC plus HAP group vs ten [ 4 % ] in the EUC alone group ; p=1·00 ) . Interpretation HAP delivered by lay counsellors plus EUC was better than EUC alone was for patients with moderately severe to severe depression in routine primary care in Goa , India . HAP was readily accepted by this previously untreated population and was cost-effective in this setting . HAP could be a key strategy to reduce the treatment gap for depressive disorders , the leading mental health disorder worldwide . Funding Wellcome Trust Background Experiencing systematic violence and trauma increases the risk of poor mental health outcomes ; few interventions for these types of exposures have been evaluated in low re source context s. The objective of this r and omized controlled trial was to assess the effectiveness of two psychotherapeutic interventions , Behavioral Activation Treatment for Depression ( BATD ) and Cognitive Processing Therapy ( CPT ) , in reducing depression symptoms using a locally adapted and vali date d version of the Hopkins Symptom Checklist and dysfunction measured with a locally developed scale . Secondary outcomes included posttraumatic stress , anxiety , and traumatic grief symptoms . Methods Twenty community mental health workers , working in rural health clinics , were r and omly assigned to training in one of the two interventions . The community mental health workers conducted baseline assessment s , enrolled survivors of systematic violence based on severity of depression symptoms , and r and omly assigned them to treatment or waitlist-control . Blinded community mental health workers conducted post-intervention assessment s on average five months later . Results Adult survivors of systematic violence were screened ( N = 732 ) with 281 enrolled in the trial ; 215 r and omized to an intervention ( 114 to BATD ; 101 to CPT ) and 66 to waitlist-control ( 33 to BATD ; 33 to CPT ) . Nearly 70 % ( n = 149 ) of the intervention participants completed treatment and post-intervention assessment s ; 53 ( 80 % ) waitlist-controls completed post-intervention assessment s. Estimated effect sizes for depression and dysfunction were 0.60 and 0.55 respectively , comparing BATD participants to all controls and 0.84 and 0.79 respectively , compared to BATD controls only . Estimated effect sizes for depression and dysfunction were 0.70 and 0.90 respectively comparing CPT participants to all controls and 0.44 and 0.63 respectively compared to CPT controls only . Using a permutation-based hypothesis test that is robust to the model assumptions implicit in regression models , BATD had significant effects on depression ( p = .003 ) and dysfunction ( p = .007 ) , while CPT had a significant effect on dysfunction only ( p = .004 ) . Conclusions Both interventions showed moderate to strong effects on most outcomes . This study demonstrates effectiveness of these interventions in low re source environments by mental health workers with limited prior experience . Trial Registration Clinical Trials . Gov NCT00925262 . Registered June 3 , 2009 Providing survivors of torture , imprisonment , and /or military attacks with a counseling program that includes support , skills and psychoeducation by well-trained and supervised community mental health workers can result in moderate yet meaningful improvements in depression and dysfunction . Providing survivors of torture , imprisonment , and /or military attacks with a counseling program that includes support , skills and psychoeducation by well-trained and supervised community mental health workers can result in moderate yet meaningful improvements in depression and dysfunction . ABSTRACT Supportive counseling type interventions are frequently provided to meet the mental health needs of population s in emergency and post-conflicts context s , but it has seldom been rigorously evaluated . Existing evaluations from low- and middle-income countries provide mixed evidence of effectiveness . While Iraqi Kurdistan experienced relative stability following the fall of Saddam Hussein ’s government , the population in the northern Dohuk region has continued to experience periodic violence due to conflicts with neighboring Turkey as well as more recent ISIS-associated violence . We evaluated the impact of a trauma-informed support , skills , and psychoeducation intervention provided by community mental health workers ( CMHWs ) on depressive symptoms and dysfunction ( primary outcomes ) as well as post-traumatic stress , traumatic grief , and anxiety symptoms ( secondary outcomes ) . Between June 2009 and June 2010 , 295 adults were screened ; 209 ( 71 % ) met eligibility criteria ( trauma exposure and a symptom severity score indicating significant distress and functional impairment , among others ) and consented to participate . Of these , 159 were r and omized to supportive counseling while 50 were r and omized to a waitlist control condition . Comparing average symptom severity scores post-treatment among those in the intervention group with those in the waitlist control group , the supportive counseling program had statistically and clinical ly significant impacts on the primary outcomes of depression ( Cohen ’s d , 0.57 ; P = .02 ) and dysfunction ( Cohen ’s d , 0.53 ; P = .03 ) and significant but smaller impacts on anxiety . Although studies by the same research team of psychotherapeutic interventions in other parts of Kurdistan and in southern Iraq found larger effects , this study adds to the global research literature on mental health and psychosocial support and shows that a well-trained and supervised program of trauma-informed support , skills , and psychoeducation that emphasizes the therapeutic relationship can also be effective Background Personalized healthcare relies on the identification of factors explaining why individuals respond differently to the same intervention . Analyses identifying such factors , so called predictors and moderators , have their own set of assumptions and limitations which , when violated , can result in misleading cl aims , and incorrect actions . The aim of this study was to develop a checklist for critically appraising the results of predictor and moderator analyses by combining recommendations from published guidelines and experts in the field . Methods C and i date criteria for the checklist were retrieved through systematic search es of the literature . These criteria were evaluated for appropriateness using a Delphi procedure . Two Delphi rounds yielded a pilot checklist , which was tested on a set of papers included in a systematic review on reinforced home-based palliative care . The results of the pilot informed a third Delphi round , which served to finalize the checklist . Results Forty-nine appraisal criteria were identified in the literature . Feedback was obtained from fourteen experts from (bio)statistics , epidemiology and other associated fields elicited via three Delphi rounds . Additional feedback from other research ers was collected in a pilot test . The final version of our checklist included seventeen criteria , covering the design ( e.g. a priori plausibility ) , analysis ( e.g. use of interaction tests ) and results ( e.g. complete reporting ) of moderator and predictor analysis , together with the transferability of the results ( e.g. clinical importance ) . There are criteria both for individual papers and for bodies of evidence . Conclusions The proposed checklist can be used for critical appraisal of reported moderator and predictor effects , as assessed in r and omized or non-r and omized studies using individual participant or aggregate data . This checklist is accompanied by a user ’s guide to facilitate implementation . Its future use across a wide variety of research domains and study types will provide insights about its usability and feasibility Background Gender-based violence ( GBV ) represents a major cause of psychological morbidity worldwide , and particularly in low- and middle-income countries ( LMICs ) . Although there are effective treatments for common mental disorders associated with GBV , they typically require lengthy treatment programs that may limit scaling up in LMICs . The aim of this study was to test the effectiveness of a new 5-session behavioural treatment called Problem Management Plus ( PM+ ) that lay community workers can be taught to deliver . Methods and findings In this single-blind , parallel , r and omised controlled trial , adult women who had experienced GBV were identified through community screening for psychological distress and impaired functioning in Nairobi , Kenya . Participants were r and omly allocated in a 1:1 ratio either to PM+ delivered in the community by lay community health workers provided with 8 days of training or to facility-based enhanced usual care ( EUC ) provided by community nurses . Participants were aware of treatment allocation , but research assessors were blinded . The primary outcome was psychological distress as measured by the total score on the 12-item General Health Question naire ( GHQ-12 ) assessed at 3 months after treatment . Secondary outcomes were impaired functioning ( measured by the WHO Disability Adjustment Schedule [ WHODAS ] ) , symptoms of posttraumatic stress ( measured by the Posttraumatic Stress Disorder Checklist [ PCL ] ) , personally identified problems ( measured by Psychological Outcome Profiles [ PSYCHLOPS ] ) , stressful life events ( measured by the Life Events Checklist [ LEC ] ) , and health service utilisation . Between 15 April 2015 and 20 August 2015 , 1,393 women were screened for eligibility on the basis of psychological distress and impaired functioning . Of these , 518 women ( 37 % ) screened positive , of whom 421 ( 81 % ) were women who had experienced GBV . Of these 421 women , 209 were assigned to PM+ and 212 to EUC . Follow-up assessment s were completed on 16 January 2016 . The primary analysis was intention to treat and included 53 women in PM+ ( 25 % ) and 49 women in EUC ( 23 % ) lost to follow-up . The difference between PM+ and EUC in the change from baseline to 3 months on the GHQ-12 was Output:	INTERPRETATION Psychological interventions treat anxiety effectively in women with current or recent intimate partner violence exposure in LMICs when delivered by appropriately trained and supervised health-care staff , even when not tailored for this population or targeting intimate partner violence directly .
MS21312	*TASK* the task is to summarize an input biomedical literature in six sentences *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 PURPOSE A traditional end point for colon adjuvant clinical trials is overall survival ( OS ) , with 5 years demonstrating adequate follow-up . A shorter-term end point providing convincing evidence to allow treatment comparisons could significantly speed the translation of advances into practice . METHODS Individual patient data were pooled from 18 r and omized phase III colon cancer adjuvant clinical trials . Trials included 43 arms , with a pooled sample size of 20,898 patients . The primary hypothesis was that disease-free survival ( DFS ) , with 3 years of follow-up , is an appropriate primary end point to replace OS with 5 years of follow-up . RESULTS The recurrence rates for years 1 through 5 were 12 % , 14 % , 8 % , 5 % , and 3 % , respectively . Median time from recurrence to death was 12 months . Eighty percent of recurrences were in the first 3 years ; 91 % of patients with recurrence by 3 years died before 5 years . Correlation between 3-year DFS and 5-year OS was 0.89 . Comparing control versus experimental arms within each trial , the correlation between hazard ratios for DFS and OS was 0.92 . Within-trial log-rank testing using both DFS and OS provided the same conclusion in 23 ( 92 % ) of 25 cases . Formal measures of surrogacy were satisfied . CONCLUSION In patients treated on phase III adjuvant colon clinical trials , DFS and OS are highly correlated , both within patients and across trials . These results suggest that DFS after 3 years of median follow-up is an appropriate end point for adjuvant colon cancer clinical trials of fluorouracil-based regimens , although marginally significant DFS improvements may not translate into significant OS benefits PURPOSE We performed this phase III study to compare the irinotecan , leucovorin ( LV ) , and fluorouracil ( FU ) regimen ( FOLFIRI ) versus the oxaliplatin , LV , and FU regimen ( FOLFOX4 ) in previously untreated patients with advanced colorectal cancer . PATIENTS AND METHODS A total of 360 chemotherapy-naive patients were r and omly assigned to receive , every 2 weeks , either arm A ( FOLFIRI : irinotecan 180 mg/m(2 ) on day 1 with LV 100 mg/m(2 ) administered as a 2-hour infusion before FU 400 mg/m(2 ) administered as an intravenous bolus injection , and FU 600 mg/m(2 ) as a 22-hour infusion immediately after FU bolus injection on days 1 and 2 [ LV5FU2 ] ) or arm B ( FOLFOX4 : oxaliplatin 85 mg/m(2 ) on day 1 with LV5FU2 regimen ) . RESULTS One hundred sixty-four and 172 patients were assessable in arm A and B , respectively . Overall response rates ( ORR ) were 31 % in arm A ( 95 % CI , 24.6 % to 38.3 % ) and 34 % in arm B ( 95 % CI , 27.2 % to 41.5 % ; P = .60 ) . In both arms A and B , median time to progression ( TTP ; 7 v 7 months , respectively ) , duration of response ( 9 v 10 months , respectively ) , and overall survival ( OS ; 14 v 15 months , respectively ) were similar , without any statistically significant difference . Toxicity was mild in both groups : alopecia and gastrointestinal disturbances were the most common toxicities in arm A ; thrombocytopenia and neurosensorial were the most common toxicities in arm B. Grade 3 to 4 toxicities were uncommon in both arms , and no statistical significant difference was observed . CONCLUSION There is no difference in ORR , TTP , and OS for patients treated with the FOLFIRI or FOLFOX4 regimen . Both therapies seemed effective as first-line treatment in these patients . The difference between these two combination therapies is mainly in the toxicity profile Output:	BRAF mutation decreases tumor response in first-line treatment whether cetuximab was given or not in patients with KRAS wild-type , and anti-EGFR MoAb produces a clear benefit in response rate in patients with BRAF and KRAS wild-type
MS21313	*TASK* the task is to summarize an input biomedical literature in six sentences *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 : Pathophysiological mechanisms underlying spinal cord injury ( SCI ) partially involve edema and formation of a hematoma . Myelotomy seems to be a promising intervention . However , the appropriate timing of myelotomy is still unknown in SCI . Here we aim ed to determine the timing of microsurgical myelotomy in an animal model of SCI . Methods : The SCI model was contusion-induced with a new york university impactor . Sixty-five adult female rats were r and omly divided into the following groups : laminectomy alone ( the ‘ sham group ’ , SG ) , laminectomy plus contusion ( the ‘ contusion group ’ , CG ) or laminectomy plus contusion followed by myelotomy at 8 , 24 or 48 h ( 8 h-MTG [ myelotomy-treated group ] , 24 h-MTG or 48 h-MTG ) . Functional recovery was evaluated via the open field test and the inclined plane test every week after SCI . The percentage of spared white matter area ( SWMA ) and ultrastructure characteristics of the injured dorsolateral spinal cord were determined on the 42nd day after SCI . Results : Compared with the CG , myelotomy at 8 h-MTG or 24 h-MTG greatly improved the BASSO-BEATTIE- BRESNAHAN scores ( P<0.008 ) , whereas the 48 h-MTG showed less efficacy ( P=0.023 ) . All myelotomy groups showed higher mean angle values in an inclined plane test ( P<0.005 ) and had greater percentages of SWMA than the CG . Rats in the 24 h-MTG showed a higher intra-axonal fraction and myelin fraction than those in 48 h-MTG ( P<0.005 ) . Conclusion : Myelotomy up to 48 h after SCI improves recovery in rats . The potential time window of myelotomy may be between 8 and 24 h after SCI Background There is convincing pre clinical evidence that early decompression in the setting of spinal cord injury ( SCI ) improves neurologic outcomes . However , the effect of early surgical decompression in patients with acute SCI remains uncertain . Our objective was to evaluate the relative effectiveness of early ( < 24 hours after injury ) versus late ( ≥24 hours after injury ) decompressive surgery after traumatic cervical SCI . Methods We performed a multicenter , international , prospect i ve cohort study ( Surgical Timing in Acute Spinal Cord Injury Study : STASCIS ) in adults aged 16–80 with cervical SCI . Enrolment occurred between 2002 and 2009 at 6 North American centers . The primary outcome was ordinal change in ASIA Impairment Scale ( AIS ) grade at 6 months follow-up . Secondary outcomes included assessment s of complications rates and mortality . Findings A total of 313 patients with acute cervical SCI were enrolled . Of these , 182 underwent early surgery , at a mean of 14.2(±5.4 ) hours , with the remaining 131 having late surgery , at a mean of 48.3(±29.3 ) hours . Of the 222 patients with follow-up available at 6 months post injury , 19.8 % of patients undergoing early surgery showed a ≥2 grade improvement in AIS compared to 8.8 % in the late decompression group ( OR = 2.57 , 95 % CI:1.11,5.97 ) . In the multivariate analysis , adjusted for preoperative neurological status and steroid administration , the odds of at least a 2 grade AIS improvement were 2.8 times higher amongst those who underwent early surgery as compared to those who underwent late surgery ( OR = 2.83 , 95 % CI:1.10,7.28 ) . During the 30 day post injury period , there was 1 mortality in both of the surgical groups . Complications occurred in 24.2 % of early surgery patients and 30.5 % of late surgery patients ( p = 0.21 ) . Conclusion Decompression prior to 24 hours after SCI can be performed safely and is associated with improved neurologic outcome , defined as at least a 2 grade AIS improvement at 6 months follow-up Using data from the Second National Acute Spinal Cord Injury Study ( NASCIS II ) , the authors sought to characterize the role of surgery in the management of traumatic spinal cord injury and to examine the interaction between pharmacological treatment and surgery . Patients who did not undergo surgery had more severe spinal cord injuries initially than those who had surgery . However , no differences in neurological improvement at 1-year follow-up were found between those who underwent surgery and those who did not . The results suggest that either early surgery ( < or = 25 hours after injury ) or late surgery ( > 200 hours ) may be associated with increased neurological recovery , particularly motor function , but these results are equivocal . Surgery was not shown to interact with pharmacological treatments , indicating that the effect of drug treatment in NASCIS II , reported elsewhere , is not influenced by surgery . Other independent variables that best predicted improvement in motor score were age of 25 years or younger , incomplete injury , and lower baseline emergency department neurological scores . This study does not provide clinical ly relevant evidence concerning the efficacy of timing or the value of surgery in treating patients with spinal cord injuries . A r and omized study on the timing and efficacy of spinal cord surgery is needed to obtain valid comparisons of the efficacy of surgical treatments BACKGROUND CONTEXT Surgical treatment in the setting of central cord syndrome ( CCS ) has become safer since Schneider 's original description . It is generally accepted that a decompressive surgical intervention is a valid treatment option in a patient with CCS and radiographic evidence of spinal cord compression . The optimal timing of surgical intervention for CCS remains controversial . PURPOSE To review a single institution 's experience managing CCS , with particular emphasis on surgical versus medical management , timing of surgery , neurologic outcomes , hospital length of stay , and complications . STUDY DESIGN Retrospective review . PATIENT SAMPLE One hundred twenty-six patients diagnosed with CCS were treated at Wake Forest University Baptist Medical Center between June 1985 and September 2006 . OUTCOME MEASURES Neurological outcomes were measured using the Frankel grading scale . Other outcome measures included hospital and intensive care unit ( ICU ) length of stay and complication profiles . METHODS A retrospective chart review was performed on patients admitted to Wake Forest University Baptist Medical Center with the diagnosis of traumatic central cord injury from June 1985 to September 2006 with institutional review board approval . Neurologic status was recorded on presentation and at maximum follow-up using the Frankel classification . The surgical cohort was stratified into three subgroups with regard to the timing of surgical intervention after injury : surgery less than 24 hours after injury , surgery greater than 24 hours after injury but during the initial admission , and delayed operative intervention on a second hospital admission . Other variables collected included ICU and hospital length of stay and complication profiles . Data analyses were performed using SPSS ( SPSS , Chicago , IL , USA ) and Excel 2002 ( Microsoft , Seattle , WA , USA ) . RESULTS A total of 126 patients treated for CCS were review ed . Sixty-seven patients received surgery compared with 59 patients managed nonoperatively . Of those managed operatively , 16 patients received surgery within 24 hours of the time of injury . There were 34 patients who received surgery greater than 24 hours after the time of injury but during their initial admission with a mean time to surgery of 6.4 days ( 5 - 52 days ) . There were 17 patients who received their operation on a second hospital admission with a mean time interval of 137 days between injury and surgery ( 3 - 209 ) . Mean follow-up was 32 months ( 1 - 210 months ) . An improvement in Frankel grade was seen in the overall operative cohort compared with those patients who received medical management alone . No statistically significant difference in neurologic outcome using Frankel grade s was identified between the surgical subgroups with regard to timing of surgery . A trend toward decreased length of stay was seen in the surgical subgroup that received surgery during their initial admission . No statistically significant difference was identified between complication rates for the operative and nonoperative groups ; however , a trend toward fewer complications and deaths was seen in those who received surgery in the first 24 hours or during the initial hospitalization . CONCLUSIONS Surgical treatment in the setting of CCS has become safer since Schneider 's original description . Acknowledging its numerous limitations , this retrospective study supports surgical intervention in the setting of CCS as a safe effective management option . Improved Frankel grade s were identified in those patients managed surgically compared with those receiving medical management alone . The data further shed light on the safety and potential benefits of early operative intervention for acute CCS compared with delayed surgical treatment . A prospect i ve r and omized controlled trial is needed to definitively compare surgical versus medical management and /or early versus delayed surgical treatment in the setting of traumatic CCS Study Design Prospect i ve observational study . Purpose To assess the clinical outcome after early versus late decompression for traumatic cervical cord injury . Overview of Literature Traumatic spinal cord injury is common globally with the most tragic outcomes in the cervical spine . Although recent studies have shown that early decompression results in more favourable outcome , its authority is yet to be established . Methods Study on 98 patients with a traumatic cervical cord injury was conducted over a period of 5 years . The patients who were operated on within 24 hours of the onset of the primary injury ( n=34 ) were classified as the early group , and those who were operated on after 24 hours of the onset of the injury ( n=64 ) were categorized as the late group . The outcome of both the groups was assessed using the American Spinal Injury Association ( ASIA ) Impairment Scale ( AIS ) at the 6-month follow-up . Results The patients in the early group were operated on at a mean time of 18.4 hours ( range , 13 - 24 hours ) while patients were operated on at a mean time of 52.7 hours ( range , 31 - 124 hours ) in the late group . At the 6-month follow-up , 7 ( 23.3 % ) in the early group and 5 ( 8.7 % ) in the late group showed > 2 grade improvement in the AIS . Conclusions The results of patients undergoing decompression within 24 hours of the injury are better than those who are operated on later . An attempt should be made to decompress the traumatic cervical spine early in all possible cases STUDY DESIGN A prospect i ve , longitudinal study of multiply injured patients treated with segmental instrumentation for spinal fractures with a minimum 2-year follow-up . OBJECTIVES To determine whether urgent stabilization of spinal fractures in severely injured patients increases the risk of surgery compared with early treatment and historical results . SUMMARY AND BACKGROUND DATA Opinion in clinical studies is divided about whether operative treatment offers an advantage over nonoperative treatment in isolated spine fractures . Concomitant trauma is rarely discussed relative to decision making or surgical timing . Urgent stabilization of long-bone fractures improves survival and outcome in polytrauma patients . To date , urgent treatment of spine fractures in polytrauma patients has not been considered in the literature . METHODS Seventy-five consecutive patients treated with segmental instrumentation for spinal trauma were observed prospect ively to assess perioperative and longterm outcome . Twenty-seven patients with severe polytrauma ( injury severity score , > 26 ) were separately analyzed . Perioperative and postoperative results were analyzed relative to timing of surgery , injury severity score , and surgical approach . Urgent treatment was defined as that provided within 24 hours of the spinal injury , and early treatment was defined as that provided between 24 and 72 hours after injury . RESULTS Twenty-five patients ( 93 % ) sustained two or more major injuries in addition to the spine fracture , and 17 of 27 ( 63 % ) had neurologic injury . The mean injury severity score approached or exceeded the LD50 ( 50 % expected mortality ) in each group--36.0 for the early-treatment group and 42.0 for the urgent group -- but only one patient in each group died . There were no deep venous thromboses , pulmonary emboli , neurologic injuries , decubiti , deep wound infections , or episodes of sepsis in either group . Blood loss for anterior procedures was significantly higher in the urgent group , but estimated blood loss for posterior procedures was similar for both groups . At 49 months ' mean follow-up , no revisions were necessitated by the urgent spinal treatment . CONCLUSIONS Urgent spinal stabilization is safe and appropriate in polytrauma patients when progressive neurologic deficit , thoracoabdominal trauma , or fracture instability increase the risks of delayed treatment Study Design . A prospect i ve analysis evaluating neurologic outcome after early versus late surgery for cervical spinal cord trauma . Objectives . The study was conducted to determine whether neurologic and functional outcome is improved in traumatic cervical spinal cord‐injured patients ( C3‐T1 , American Spinal Injury Association grade s A‐D ) who had early surgery ( < 72 hours after spinal cord injury ) compared with those patients who had late surgery ( > 5 days after spinal cord injury ) . Summary of Background Data . There is considerable controversy as to the appropriate timing of surgical decompression and stabilization for cervical spinal cord trauma . There have been numerous retrospective studies , but no prospect i ve studies , to determine whether neurologic outcome is best after early versus late surgical treatment for cervical spinal cord injury . Methods . Patients meeting appropriate inclusion criteria were r and omized to an early ( < 72 hours after spinal cord injury ) or late ( > 5 days after spinal cord injury ) surgical treatment protocol . The neuro Output:	There was significant variability in the definition of early and late decompression in both clinical and pre clinical studies . Pre clinical data were in favor of early decompression . From a clinical st and point , there was only level II evidence proving safety and feasibility of early decompression with no definite evidence of improved outcome for any of the two groups . There is growing evidence in favor of early decompression following SCI . Early decompression was proven to be clinical ly safe and feasible , but there is still no definite proof that early decompression leads to improved outcomes .
MS21314	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Effective internet-based programs for depression usually incorporate a component that provides telephone or email contact . Open access websites , without such contact , show high rates of attrition and poorer outcomes . The present study was design ed as an exploratory investigation of the parameters that influence the effectiveness and retention of users on open access websites . We investigated whether brief cognitive behaviour therapy ( CBT ) was as effective as an extended version , whether add-on components of behaviour therapy or stress management contributed to positive outcomes , and whether longer programs were associated with greater attrition . METHOD An online r and omized controlled trial ( RCT ) was conducted between 13 January 2005 and 26 May 2005 ( 19 weeks ) . A total of 2794 registrants ( 1846 women and 948 men ; median age category 35 - 44 years ) with elevated scores on the Goldberg Depression Scale of 5.96 ( S.D.=2.09 ) elected online to be r and omized to one of six versions of a CBT website . The versions were compiled consisting of various components of brief CBT , extended CBT , behaviour strategies , stress management and problem solving . RESULTS A total of 20.4 % of participants completed the assigned intervention . The interaction of measurement occasion and treatment version was significant [ F(13,131)=2.20 , p=0.01 ] . A single module of brief introductory CBT was not effective in reducing depression symptoms . However , extended CBT with or without the addition of behaviour strategies result ed in the reduction of depression . CONCLUSIONS Brief CBT-based interventions are not as effective as extended interventions . However , longer programs are associated with higher rates of dropout Background Research increasingly supports the conclusion that well- design ed programs delivered over the Internet can produce significant weight loss compared to r and omized controlled conditions . Much less is known about four important issues addressed in this study : ( 1 ) which recruitment methods produce higher eHealth participation rates , ( 2 ) which patient characteristics are related to enrollment , ( 3 ) which characteristics are related to level of user engagement in the program , and ( 4 ) which characteristics are related to continued participation in project assessment s. Methods We recruited overweight members of three health maintenance organizations ( HMOs ) to participate in an entirely Internet-mediated weight loss program developed by HealthMedia , Inc. Two different recruitment methods were used : personal letters from prevention directors in each HMO , and general notices in member newsletters . The personal letters were sent to members diagnosed with diabetes or heart disease and , in one HMO , to a general membership sample in a particular geographic location . Data were collected in the context of a 2 × 2 r and omized controlled trial , with participants assigned to receive or not receive a goal setting intervention and a nutrition education intervention in addition to the basic program . Results A total of 2311 members enrolled . Bivariate analyses on aggregate data revealed that personalized mailings produced higher enrollment rates than member newsletters and that members with diabetes or heart disease were more likely to enroll than those without these diagnoses . In addition , males , those over age 60 , smokers , and those estimated to have higher medical expenses were less likely to enroll ( all P < .001 ) . Males and those in the combined intervention were less likely to engage initially , or to continue to be engaged with their Web program , than other participants . In terms of retention , multiple logistic regressions revealed that enrollees under age 60 ( P < .001 ) and those with higher baseline self-efficacy were less likely to participate in the 12-month follow-up ( P = .03 ) , but with these exceptions , those participating were very similar to those not participating in the follow-up . Conclusions A single personalized mailing increases enrollment in Internet-based weight loss . eHealth programs offer great potential for recruiting large numbers of participants , but they may not reach those at highest risk . Patient characteristics related to each of these important factors may be different , and more comprehensive analyses of determinants of enrollment , engagement , and retention in eHealth programs are needed BACKGROUND Subthreshold depression is a highly prevalent condition and a risk factor for developing a major depressive episode . Internet-based cognitive behaviour therapy may be a promising approach for the treatment of subthreshold depression . The current study had two aims : ( 1 ) to determine whether an internet-based cognitive behaviour therapy intervention and a group cognitive behaviour therapy intervention are more effective than a waiting-list control group ; and ( 2 ) to determine whether the effect of the internet-based cognitive behaviour therapy differs from the group cognitive behaviour therapy intervention . METHOD A total of 191 women and 110 men with subthreshold depression were r and omized into internet-based treatment , group cognitive behaviour therapy ( Lewinsohn 's Coping With Depression course ) , or a waiting-list control condition . The main outcome measure was treatment response after 10 weeks , defined as the difference in pre- and post-treatment scores on the Beck Depression Inventory ( BDI ) . Missing data , a major limitation of this study , were imputed using the Multiple Imputation ( MI ) procedure Data Augmentation . RESULTS In the waiting-list control group , we found a pre- to post-improvement effect size of 0.45 , which was 0.65 in the group cognitive behaviour therapy condition and 1.00 within the internet-based treatment condition . Helmert contrasts showed a significant difference between the waiting-list condition and the two treatment conditions ( p=0.04 ) and no significant difference between both treatment conditions ( p=0.62 ) . CONCLUSIONS An internet-based intervention may be at least as effective as a commonly used group cognitive behaviour therapy intervention for subthreshold depression in people over 50 years of age The Coronary Drug Project was carried out to evaluate the efficacy and safety of several lipid-influencing drugs in the long-term treatment of coronary heart disease . The five-year mortality in 1103 men treated with clofibrate was 20.0 per cent , as compared with 20.9 per cent in 2789 men given placebo ( P = 0.55 ) . Good adherers to clofibrate , i.e. , patients who took 80 per cent of more of the protocol prescription during the five-year follow-up period , had a substantially lower five-year mortality than did poor adherers to clofibrate ( 15.0 vs. 24.6 per cent ; P = 0.00011 ) . However , similar findings were noted in the placebo group , i.e. , 15.1 per cent mortality for good adherers and 28.3 per cent for poor adherers ( P = 4.7x10 - 16 ) . These findings and various other analyses of mortality in the clofibrate and placebo groups of the project show the serious difficulty , if not impossibility , of evaluating treatment efficacy in subgroups determined by patient responses ( e.g. , adherence or cholesterol change ) to the treatment protocol after r and omization CONTEXT Rapid increases in access to the Internet have made it a viable mode for public health intervention . No controlled studies have evaluated this re source for weight loss . OBJECTIVE To determine whether a structured Internet behavioral weight loss program produces greater initial weight loss and changes in waist circumference than a weight loss education Web site . DESIGN R and omized , controlled trial conducted from April to December 1999 . SETTING AND PARTICIPANTS Ninety-one healthy , overweight adult hospital employees aged 18 to 60 years with a body mass index of 25 to 36 kg/m(2 ) . Analyses were performed for the 65 who had complete follow-up data . INTERVENTIONS Participants were r and omly assigned to a 6-month weight loss program of either Internet education ( education ; n = 32 with complete data ) or Internet behavior therapy ( behavior therapy ; n = 33 with complete data ) . All participants were given 1 face-to-face group weight loss session and access to a Web site with organized links to Internet weight loss re sources . Participants in the behavior therapy group received additional behavioral procedures , including a sequence of 24 weekly behavioral lessons via e-mail , weekly online su bmi ssion of self-monitoring diaries with individualized therapist feedback via e-mail , and an online bulletin board . MAIN OUTCOME MEASURES Body weight and waist circumference , measured at 0 , 3 , and 6 months , compared the 2 intervention groups . RESULTS Repeated- measures analyses showed that the behavior therapy group lost more weight than the education group ( P = .005 ) . The behavior therapy group lost a mean ( SD ) of 4.0 ( 2.8 ) kg by 3 months and 4.1 ( 4.5 ) kg by 6 months . Weight loss in the education group was 1.7 ( 2.7 ) kg at 3 months and 1.6 ( 3.3 ) kg by 6 months . More participants in the behavior therapy than education group achieved the 5 % weight loss goal ( 45 % vs 22 % ; P = .05 ) by 6 months . Changes in waist circumference were also greater in the behavior therapy group than in the education group at both 3 months ( P = .001 ) and 6 months ( P = .005 ) . CONCLUSIONS Participants who were given a structured behavioral treatment program with weekly contact and individualized feedback had better weight loss compared with those given links to educational Web sites . Thus , the Internet and e-mail appear to be viable methods for delivery of structured behavioral weight loss programs BACKGROUND Major depression can be treated by means of cognitive-behavioural therapy , but as skilled therapists are in short supply there is a need for self-help approaches . Many individuals with depression use the internet for discussion of symptoms and to share their experience . AIMS To investigate the effects of an internet-administered self-help programme including participation in a monitored , web-based discussion group , compared with participation in web-based discussion group only . METHOD A r and omised controlled trial was conducted to compare the effects of internet-based cognitive-behavioural therapy with minimal therapist contact ( plus participation in a discussion group ) with the effects of participation in a discussion group only . RESULTS Internet-based therapy with minimal therapist contact , combined with activity in a discussion group , result ed in greater reductions of depressive symptoms compared with activity in a discussion group only ( waiting-list control group ) . At 6 months ' follow-up , improvement was maintained to a large extent . CONCLUSIONS Internet-delivered cognitive cognitive-behavioural therapy should be pursued further as a complement or treatment alternative for mild-to-moderate depression Proper r and omisation means little if investigators can not include all r and omised participants in the primary analysis . Participants might ignore follow-up , leave town , or take aspartame when instructed to take aspirin . Exclusions before r and omisation do not bias the treatment comparison , but they can hurt generalisability . Eligibility criteria for a trial should be clear , specific , and applied before r and omisation . Readers should assess whether any of the criteria make the trial sample atypical or unrepresentative of the people in which they are interested . In principle , assessment of exclusions after r and omisation is simple : none are allowed . For the primary analysis , all participants enrolled should be included and analysed as part of the original group assigned ( an intent-to-treat analysis ) . In reality , however , losses frequently occur . Investigators should , therefore , commit adequate re sources to develop and implement procedures to maximise retention of participants . Moreover , research ers should provide clear , explicit information on the progress of all r and omised participants through the trial by use of , for instance , a trial profile . Investigators can also do secondary analyses on , for instance , per- protocol or as-treated participants . Such analyses should be described as secondary and non-r and omised comparisons . Mish and ling of exclusions causes serious method ological difficulties . Unfortunately , some explanations for mish and ling exclusions intuitively appeal to readers , disguising the seriousness of the issues . Creative mismanagement of exclusions can undermine trial validity BACKGROUND Computerised cognitive-behavioural therapy ( CCBT ) might offer a solution to the current undertreatment of depression . AIMS To determine the clinical effectiveness of online , unsupported CCBT for depression in primary care . METHOD Three hundred and three people with depression were r and omly allocated to one of three groups : Colour Your Life ; treatment as usual ( TAU ) by a general practitioner ; or Colour Your Life and TAU combined . Colour Your Life is an online , multimedia , interactive CCBT programme . No assistance was offered . We had a 6-month follow-up period . RESULTS No significant differences in outcome between the three interventions were found in the intention-to-treat and per protocol analyses . CONCLUSIONS Online , unsupported CCBT did not outperform usual care , and the combination of both did not have additional effects . Decrease in depressive symptoms in people with moderate to severe depression was moderate in all three interventions . Online CCBT without support is not beneficial for all individuals with depression In this paper we document the experience of participating in novel r and omised controlled trials for panic disorder - where face-to-face and Internet delivery of cognitive behavioural therapy are compared . Our analysis is based on 18 months of observation and in-depth interviews with 10 trial participants and 8 trialists in Victoria , Australia . We argue that the participants are positioned as active health consumers and approach the trial as they would other self-help practice s. High levels of individual responsibility are assumed of participants in these trials , which they accept by approaching the trials reflexively and search ing for information and strategies they can employ while building their health literacy on panic disorder . Although the research ers set the parameters of the treatment and interaction , increasingly the participants choose the extent to which they will comply with their defined role . For the participants the trial is one of the ' pick and mix ' options of available treatment and we suggest it is a compelling example of contemporary health consumption Background Psychoeducational programs are increasingly being delivered over the Internet . We created an Internet-based , cognitive therapy , self-help program to be used as a st and -alone intervention for mild-to-moderate Output:	However , logins appeared to be the measure of adherence most consistently related to outcomes in physical health interventions , while module completion was found to be most related to outcomes in psychological health interventions . There is large variation in the reporting of adherence and the association of adherence with outcomes . Physical and psychological outcomes seem influenced by different types of adherence . A composite measure encompassing time online , activity completion , and active engagements with the intervention may be the best measure of adherence .
MS21315	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Aims : Assess the efficacy and safety of saxagliptin added to a submaximal sulphonylurea dose vs. uptitration of sulphonylurea monotherapy in patients with type 2 diabetes and inadequate glycaemic control with sulphonylurea monotherapy . Methods and patients : A total of 768 patients ( 18–77 years ; HbA1c screening ≥ 7.5 to ≤ 10.0 % ) were r and omised and treated with saxagliptin 2.5 or 5 mg in combination with glyburide 7.5 mg vs. glyburide 10 mg for 24 weeks . Blinded uptitration glyburide was allowed in the glyburide-only arm to a maximum total daily dose of 15 mg . Efficacy analyses were performed using ANCOVA and last-observation-carried-forward methodology . Results : At week 24 , 92 % of glyburide-only patients were uptitrated to a total glyburide dose of 15 mg/day . Saxagliptin 2.5 and 5 mg provided statistically significant adjusted mean decreases from baseline to week 24 vs. uptitrated glyburide , respectively , in HbA1c ( −0.54 % , −0.64 % vs. + 0.08 % ; both p < 0.0001 ) and fasting plasma glucose ( −7 , −10 vs. + 1 mg/dl ; p = 0.0218 and p = 0.002 ) . The proportion of patients achieving an HbA1c < 7 % was greater for saxagliptin 2.5 and 5 mg vs. uptitrated glyburide ( 22.4 % and 22.8 % vs. 9.1 % ; both p < 0.0001 ) . Postpr and ial glucose area under the curve was reduced for saxagliptin 2.5 and 5 mg vs. uptitrated glyburide ( −4296 and −5000 vs. + 1196 mg·min/dl ; both p < 0.0001 ) . Adverse event occurrence was similar across all groups . Reported hypoglycaemic events were not statistically significantly different for saxagliptin 2.5 ( 13.3 % ) and 5 mg ( 14.6 % ) vs. uptitrated glyburide ( 10.1 % ) . Conclusion : Saxagliptin added to submaximal glyburide therapy led to statistically significant improvements vs. uptitration of glyburide alone across key glycaemic parameters and was generally well tolerated Abstract Background : The lack of adequate glycaemic control for patients with type 2 diabetes mellitus ( T2DM ) , especially with existing second-line therapies , represents an unmet medical need . Of the newer therapies , the incretin-based medicines , such as saxagliptin , look promising to consoli date second-line pharmacotherapy . Objective : This study evaluates the long-term economic consequences of saxagliptin versus sulfonylurea ( glipizide ) as second-line therapy when used in combination with metformin after failure of monotherapy treatment with metformin , in patients with T2DM in Germany . Methods : A published discrete event simulation model with a fixed-time increment was used to model the effects of different treatment scenarios over a 40-year ( life- ) time horizon . Disease progression was modelled using evidence from the United Kingdom Prospect i ve Diabetes Study ( UKPDS ) 68 . The treatment sequence matched that of published German guidelines , and efficacy and safety data were derived from published sources . The model assumes that quality -adjusted life-years ( QALYs ) are affected by complications , hypoglycaemic events and weight change over a lifetime . Costs were specific to the German setting , where sulfonylureas are generic . Costs and effects were discounted annually at 3 % . The extended perspective of the national sick funds was adopted , and recommendations from the Institute for Quality and Efficiency in Health Care ( IQWiG ) were considered . Results : In the base-case analysis , treatment with saxagliptin plus metformin was associated with a lower incidence of both symptomatic and severe hypoglycaemic events , result ing in an incremental benefit of 0.12 QALYs and an incremental cost-effectiveness ratio ( ICER ) of € 13 931 per QALY gained compared with sulfonylurea plus metformin ( year of costing 2009 ) . Modest reductions in all macro- and microvascular complications were seen in those receiving saxagliptin plus metformin compared with sulfonylurea plus metformin . Sensitivity analysis showed that treatment-related weight changes , as a risk factor for complications , represent the most influential driver of cost effectiveness . Conclusion : The study demonstrated improved outcomes with saxagliptin at a cost that would likely be considered acceptable in the German setting . Furthermore , the findings of the sensitivity analysis suggest that the results are robust to various assumptions concerning input variables and modelling assumptions AIM To assess the efficacy and safety of a 24-week treatment with sitagliptin , a highly selective once-daily oral dipeptidyl peptidase-4 ( DPP-4 ) inhibitor , in patients with type 2 diabetes who had inadequate glycaemic control [ glycosylated haemoglobin ( HbA(1c ) ) > or=7.5 % and < or=10.5 % ] while on glimepiride alone or in combination with metformin . METHODS After a screening , diet/exercise run-in and drug wash-off period , a glimepiride + /- metformin dose titration/stabilization period and a 2-week , single-blind placebo run-in , 441 patients ( of ages 18 - 75 years ) were r and omized to receive the addition of sitagliptin 100 mg once daily or placebo in a 1 : 1 ratio for 24 weeks . Of these patients , 212 were on glimepiride ( > or=4 mg/day ) monotherapy and 229 were on glimepiride ( > or=4 mg/day ) plus metformin ( > or=1,500 mg/day ) combination therapy . Patients exceeding pre-specified glycaemic thresholds during the double-blind treatment period were provided open-label rescue therapy ( pioglitazone ) until study end . The primary efficacy analysis evaluated the change in HbA(1c ) from baseline to Week 24 . Secondary efficacy endpoints included fasting plasma glucose ( FPG ) , 2-h post-meal glucose and lipid measurements . RESULTS Mean baseline HbA(1c ) was 8.34 % in the sitagliptin and placebo groups . After 24 weeks , sitagliptin reduced HbA(1c ) by 0.74 % ( p < 0.001 ) relative to placebo . In the subset of patients on glimepiride plus metformin , sitagliptin reduced HbA(1c ) by 0.89 % relative to placebo , compared with a reduction of 0.57 % in the subset of patients on glimepiride alone . The addition of sitagliptin reduced FPG by 20.1 mg/dl ( p < 0.001 ) and increased homeostasis model assessment -beta , a marker of beta-cell function , by 12 % ( p < 0.05 ) relative to placebo . In patients who underwent a meal tolerance test ( n = 134 ) , sitagliptin decreased 2-h post-pr and ial glucose ( PPG ) by 36.1 mg/dl ( p < 0.001 ) relative to placebo . The addition of sitagliptin was generally well tolerated , although there was a higher incidence of overall ( 60 vs. 47 % ) and drug-related adverse experiences ( AEs ) ( 15 vs. 7 % ) in the sitagliptin group than in the placebo group . This was largely because of a higher incidence of hypoglycaemia AEs ( 12 vs. 2 % , respectively ) in the sitagliptin group compared with the placebo group . Body weight modestly increased with sitagliptin relative to placebo ( + 0.8 vs. -0.4 kg ; p < 0.001 ) . CONCLUSIONS Sitagliptin 100 mg once daily significantly improved glycaemic control and beta-cell function in patients with type 2 diabetes who had inadequate glycaemic control with glimepiride or glimepiride plus metformin therapy . The addition of sitagliptin was generally well tolerated , with a modest increase in hypoglycaemia and body weight , consistent with glimepiride therapy and the observed degree of glycaemic improvement AIM To assess the efficacy and safety of saxagliptin vs. glipizide as add-on therapy to metformin in patients with type 2 diabetes mellitus and inadequate glycaemic control on metformin alone . METHODS AND PATIENTS A total of 858 patients [ age ≥ 18 years ; glycated haemoglobin ( HbA(1c ) ) > 6.5 - 10.0 % ; on stable metformin doses ≥ 1500 mg/day ] were r and omised 1 : 1 to saxagliptin 5 mg/day or glipizide up-titrated as needed from 5 to 20 mg/day for 52 weeks . The primary objective was to assess if the change from baseline HbA(1c ) achieved with saxagliptin plus metformin was non-inferior to glipizide plus metformin . RESULTS The per- protocol analysis demonstrated non-inferiority of saxagliptin vs. glipizide ; adjusted mean changes from baseline HbA(1c ) were -0.74 % vs. -0.80 % , respectively ; the between-group difference was 0.06 % ( 95 % CI , -0.05 % to 0.16 % ) . Treatment with saxagliptin vs. glipizide was associated with a significantly smaller proportion of patients with hypoglycaemic events ( 3.0 % vs. 36.3 % ; p < 0.0001 ) and a divergent impact on body weight ( adjusted mean change from baseline -1.1 kg with saxagliptin vs. 1.1 kg with glipizide ; p < 0.0001 ) . There was a significantly smaller rise in HbA(1c ) ( % /week ) from week 24 to 52 with saxagliptin vs. glipizide ( 0.001 % vs. 0.004 % ; p = 0.04 ) indicating a sustained glycaemic effect beyond week 24 . Excluding hypoglycaemic events , the proportion of patients experiencing adverse events ( AEs ) was similar ( 60.0 % saxagliptin vs. 56.7 % glipizide ) ; treatment-related AEs were less common with saxagliptin vs. glipizide ( 9.8 % vs. 31.2 % ) , attributable to the higher frequency of hypoglycaemia in glipizide patients . Discontinuation rates result ing from AEs were similar ( ∼4 % ) . CONCLUSION Saxagliptin plus metformin was well tolerated , provided a sustained HbA(1c ) reduction over 52 weeks , and was non-inferior to glipizide plus metformin , with reduced body weight and a significantly lower risk of hypoglycaemia BACKGROUND Severe hypoglycemia may increase the risk of a poor outcome in patients with type 2 diabetes assigned to an intensive glucose-lowering intervention . We analyzed data from a large study of intensive glucose lowering to explore the relationship between severe hypoglycemia and adverse clinical outcomes . METHODS We examined the associations between severe hypoglycemia and the risks of macrovascular or microvascular events and death among 11,140 patients with type 2 diabetes , using Cox proportional-hazards models with adjustment for covariates measured at baseline and after r and omization . RESULTS During a median follow-up period of 5 years , 231 patients ( 2.1 % ) had at least one severe hypoglycemic episode ; 150 had been assigned to intensive glucose control ( 2.7 % of the 5571 patients in that group ) , and 81 had been assigned to st and ard glucose control ( 1.5 % of the 5569 patients in that group ) . The median times from the onset of severe hypoglycemia to the first major macrovascular event , the first major microvascular event , and death were 1.56 years ( interquartile range , 0.84 to 2.41 ) , 0.99 years ( interquartile range , 0.40 to 2.17 ) , and 1.05 years ( interquartile range , 0.34 to 2.41 ) , respectively . During follow-up , severe hypoglycemia was associated with a significant increase in the adjusted risks of major macrovascular events ( hazard ratio , 2.88 ; 95 % confidence interval [ CI ] , 2.01 to 4.12 ) , major microvascular events ( hazard ratio , 1.81 ; 95 % CI , 1.19 to 2.74 ) , death from a cardiovascular cause ( hazard ratio , 2.68 ; 95 % CI , 1.72 to 4.19 ) , and death from any cause ( hazard ratio , 2.69 ; 95 % CI , 1 Output:	Conclusions and Implication s of Key Findings This study provides the first systematic evaluation of DPP-4 inhibitors for patients with type 2 diabetes . It found that , in patients with type 2 diabetes who do not achieve glycemic targets with antidiabetic monotherapy , DPP-4 inhibitors as add-on treatment may represent a cost-effective option compared with sulfonylureas and insulin .
MS21316	*TASK* the task is to summarize an input biomedical literature in six sentences *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 paper reports the results of a study to determine whether pulsed electromagnetic stimulation , applied over the mastoid bone , caused an improvement in the level of tinnitus in long-st and ing tinnitus sufferers . Fifty-eight patients from the Liverpool Tinnitus Association volunteered to take part in a double-blind placebo controlled trial . Active and placebo devices were r and omly allocated to these patients on their first visit . At the end of one week of treatment , each patient noted whether their tinnitus had completely disappeared , was improved , unchanged or made worse by the treatment Forty-five per cent of the patients who completed the trial were improved by the active device , but only 9 % by placebo ( P = 0.0013 , Mann-Whitney test ) . We suggest that electromagnetic stimulation may be an effective treatment in some tinnitus sufferers Background Tinnitus , the perception of sound and noise in absence of an auditory stimulus , has been shown to be associated with maladaptive neuronal reorganization and increased activity of the temporoparietal cortex . Transient modulation of tinnitus by repetitive transcranial magnetic stimulation ( rTMS ) indicated that these areas are critically involved in the pathophysiology of tinnitus and suggested new treatment strategies . However , the therapeutic efficacy of rTMS in tinnitus is still unclear , individual response is variable , and the optimal stimulation area disputable . Recently , continuous theta burst stimulation ( cTBS ) has been put forward as an effective rTMS protocol for the reduction of pathologically enhanced cortical excitability . Methods 48 patients with chronic subjective tinnitus will be included in this r and omized , placebo controlled , three-arm trial . The treatment consists of two trains of cTBS applied bilaterally to the secondary auditory cortex , the temporoparietal associaction cortex , or to the lower occiput ( sham condition ) every working day for four weeks . Primary outcome measure is the change of tinnitus distress as quantified by the Tinnitus Question naire ( TQ ) . Secondary outcome measures are tinnitus loudness and annoyance as well as tinnitus change during and after treatment . Audiologic and speech audiometric measurements will be performed to assess potential side effects . The aim of the present trail is to investigate effectiveness and safety of a four weeks cTBS treatment on chronic tinnitus and to compare two areas of stimulation . The results will contribute to clarify the therapeutic capacity of rTMS in tinnitus . Trial registration The trial was registered with the clinical trials register of http://www . clinical trials.gov ( NCT00518024 ) Background The heterogeneity statistic I2 , interpreted as the percentage of variability due to heterogeneity between studies rather than sampling error , depends on precision , that is , the size of the studies included . Methods Based on a real meta- analysis , we simulate artificially ' inflating ' the sample size under the r and om effects model . For a given inflation factor M = 1 , 2 , 3 , ... and for each trial i , we create a M-inflated trial by drawing a treatment effect estimate from the r and om effects model , using si2MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi = xH8viVGI8Gi = hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY = rqGqVepae9pg0db9vqaiVgFr0xfr = xfr = xc9adbaqaaeGaciGaaiaabeqaaeqabiWaaaGcbaGaem4Cam3aa0baaSqaaiabdMgaPbqaaiabikdaYaaaaaa@2FBE@/M as within-trial sampling variance . Results As precision increases , while estimates of the heterogeneity variance τ2 remain unchanged on average , estimates of I2 increase rapidly to nearly 100 % . A similar phenomenon is apparent in a sample of 157 meta-analyses . Conclusion When deciding whether or not to pool treatment estimates in a meta- analysis , the yard-stick should be the clinical relevance of any heterogeneity present . τ2 , rather than I2 , is the appropriate measure for this purpose Background Supporting 21st century health care and the practice of evidence -based medicine ( EBM ) requires ubiquitous access to clinical information and to knowledge-based re sources to answer clinical questions . Many questions go unanswered , however , due to lack of skills in formulating questions , crafting effective search strategies , and accessing data bases to identify best levels of evidence . Methods This r and omized trial was design ed as a pilot study to measure the relevancy of search results using three different interfaces for the PubMed search system . Two of the search interfaces utilized a specific framework called PICO , which was design ed to focus clinical questions and to prompt for publication type or type of question asked . The third interface was the st and ard PubMed interface readily available on the Web . Study subjects were recruited from interns and residents on an inpatient general medicine rotation at an academic medical center in the US . Thirty-one subjects were r and omized to one of the three interfaces , given 3 clinical questions , and asked to search PubMed for a set of relevant articles that would provide an answer for each question . The success of the search results was determined by a precision score , which compared the number of relevant or gold st and ard articles retrieved in a result set to the total number of articles retrieved in that set . Results Participants using the PICO templates ( Protocol A or Protocol B ) had higher precision scores for each question than the participants who used Protocol C , the st and ard PubMed Web interface . ( Question 1 : A = 35 % , B = 28 % , C = 20 % ; Question 2 : A = 5 % , B = 6 % , C = 4 % ; Question 3 : A = 1 % , B = 0 % , C = 0 % ) 95 % confidence intervals were calculated for the precision for each question using a lower boundary of zero . However , the 95 % confidence limits were overlapping , suggesting no statistical difference between the groups . Conclusion Due to the small number of search es for each arm , this pilot study could not demonstrate a statistically significant difference between the search protocol s. However there was a trend towards higher precision that needs to be investigated in a larger study to determine if PICO can improve the relevancy of search results Objective Pathophysiology of tinnitus known to accompany nearly all disorders in hearing system has not been fully understood , and therefore , there are some difficulties in evaluation and treatment thereof . The objective of the current study is to research the effectiveness of transcranial magnetic stimulation ( TMS ) application in treatment of tinnitus . Material s and Methods Sixty patients aged between 15 and 70 years who applied to a polyclinic of Ear-Nose-Throat Department , Cerrahpasa Medical Faculty , Istanbul University , because of the complaint of tinnitus between January 2009 and July 2009 were selected using simple r and om sampling method . The treatment group and the placebo group were separated r and omly as to include 30 patients . The tinnitus loudness , tinnitus frequency , tinnitus subjective score , and tinnitus h and icap inventory results were compared before application of TMS and after 1 month . Findings It was found that the difference of tinnitus h and icap inventory score within the TMS group ( before the treatment : mean , 52.76 ; SD , 15.8 ; after the treatment : mean , 44.4 ; SD , 13.57 ) was statistically significant ( P < 0.0001 ) and the difference of tinnitus h and icap inventory score within the placebo group ( before the treatment : mean , 51.46 ; SD , 15.41 ; after the treatment : mean , 51.13 ; SD , 16.86 ) was significantly insignificant ( P = 0.848 ) . When tinnitus severities determined at the beginning and end of the treatment were evaluated within each group , it was found that the difference of loudness within the group subjected to TMS was statistically significant ( P < 0.0001 ) but the difference of loudness within the placebo group was statistically insignificant ( P = 0.490 ) . When tinnitus subjective scores were evaluated within each group before and after the treatment , the difference of subjective score within the group subjected to transcranial magnetic stimulation was statistically significant ( P < 0.0001 ) , and the difference of subjective score within the placebo group was statistically significant ( P = 0.168 ) . Conclusions The studies showed that low-frequency repeating TMS is useful in the treatment of chronic tinnitus . In the current study performed on the patients with chronic tinnitus , it was shown that low-frequency repeating TMS has a statistically significant success when compared with the placebo group Objectives : Repetitive transcranial magnetic stimulation ( rTMS ) , a noninvasive method for altering cortical excitability , is becoming a therapeutic strategy in auditory research institutions worldwide . Application of inhibiting rTMS on these overactive cortical regions can result in effective tinnitus suppression . The aim of this study is to investigate the efficacy of theta-burst rTMS in patients with chronic tinnitus . Study Design : Parallel r and omized control study . Setting : Tertiary referral center . Patients : We enrolled 2 female and 20 male patients in this study . The evaluative tools included tinnitus frequency- and loudness-matching , tinnitus question naires ( TQ ) , and the Tinnitus H and icap Inventory ( THI ) . Methods : The orthogonal projection of the auditory cortex on the scalp was focalized . A figure-eight coil was placed on the surface of the skull over the targeted region with the intensity setting at 80 % of the resting motor threshold . We delivered 900 pulses of theta-burst rTMS daily for 10 business days . Main Outcome Measures : Nine of twelve patients ( 75 % ) in the active-stimulation group reported tinnitus suppression following treatment with rTMS . The treatment led to reductions of 8.58 and 8.33 in the mean TQ global and THI scores , respectively . Tinnitus loudness also decreased significantly after delivering rTMS . Results : Descriptive analysis of the TQs revealed that patients experienced significant improvements in emotional distress levels and somatic symptoms . Conclusions : Our preliminary results demonstrate that theta-burst rTMS treatments offer a method of modulating tinnitus . Patients could benefit from emotional improvements , even more than auditory perceptive relief . Further studies are needed to establish a st and ard protocol and to clarify nervous propagation along the auditory and psychological projection following treatment with rTMS We used PET to examine the pattern and time course of changes produced by repetitive transcranial magnetic stimulation ( rTMS ) over the dorsal premotor cortex ( PMd ) in healthy subjects and in patients with primary focal dystonia . Subjects received 1800 stimuli of subthreshold 1 Hz rTMS or sham stimulation to the left PMd . Afterwards , we measured regional cerebral blood flow ( rCBF ) as a marker of synaptic activity at rest and during performance of freely selected r and om finger movement . In both groups of subjects , real rTMS caused widespread bilateral decreases in neuronal activity in prefrontal , premotor , primary motor cortex , and left putamen . Conversely , rCBF in the cerebellum increased . Effects were equivalent at rest and during movement , indicating that the pattern of movement-related activation did not change . rTMS-induced changes in neuronal activity lasted for at least 1 h except in the medial aspect of the left globus pallidus . Conditioning effects on neuronal activity were larger in the patients than in the healthy subjects : there was a greater decrease of rCBF in lateral and medial premotor areas , putamen , and thalamus , including the stimulated premotor cortex , and a larger increase in cerebellar rCBF . Our findings indicate that , in healthy subjects and patients with dystonia , a single session of rTMS can produce powerful and widespread changes in regional synaptic activity as indexed by rCBF . Since the greater effects of premotor rTMS were not related to any differences in task performance , increased responsiveness of the motor system to rTMS reveals a physiological trait that characterizes patients with focal arm dystonia Background Chronic tinnitus is a frequent condition , which can have enormous impact on patient 's life and which is very difficult to treat . Accumulating data indicate that chronic tinnitus is related to dysfunctional neuronal activity in the central nervous system . Repetitive transcranial magnetic stimulation ( rTMS ) is a non-invasive method which allows to focally modulate neuronal activity . An increasing amount of studies demonstrate reduction of tinnitus after repeated sessions of low-frequency rTMS and indicate that rTMS might represent a new promising approach for the treatment of tinnitus . However available studies have been mono-centric and are characterized by small sample sizes . Therefore , this multi-center trial will test the efficacy of rTMS treatment in a large sample of chronic tinnitus patients . Methods / Design This is a r and omized , placebo-controlled , double-blind multi-center trial of two weeks 1 Hz rTMS-treatment in chronic tinnitus patients . Eligible patients will be r and omized to either 2 weeks real or sham rTMS treatment . Main eligibility criteria : male or female individuals aged 18–70 years with chronic tinnitus ( duration > 6 months ) , tinnitus-h and icap-inventory-score ≥ 38 , age-adjusted normal sensorineural hearing ( i.e. not more than 5 dB below the 10 % percentile of the appropriate age and gender group ( DIN EN ISO 7029 ) , conductive hearing loss ≤ 15dB. The primary endpoint is a change of tinnitus severity according to Output:	These data underscore the clinical effect of rTMS in the treatment of tinnitus .
MS21317	*TASK* the task is to summarize an input biomedical literature in six sentences *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 carried out a pilot study comparing satisfaction levels between psychiatric patients seen face to face ( FTF ) and those seen via videoconference . Patients who consented were r and omly assigned to one of two groups . One group received services in person ( FTF from the visiting psychiatrist ) while the other was seen using videoconferencing at 128 kbit/s . One psychiatrist provided all the FTF and videoconferencing assessment and follow-up visits . A total of 24 subjects were recruited . Three of the subjects ( 13 % ) did not attend their appointments and two subjects in each group were lost to follow-up . Thus there were nine in the FTF group and eight in the videoconferencing group . The two groups were similar in most respects . Patient satisfaction with the services was assessed using the Client Satisfaction Question naire ( CSQ-8 ) , completed four months after the initial consultation . The mean scores were 25.3 in the FTF group and 21.6 in the videoconferencing group . Although there was a trend in favour of the FTF service , the difference was not significant . Patient satisfaction is only one component of evaluation . The efficacy of telepsychiatry must also be measured relative to that of conventional , FTF care before policy makers can decide how extensively telepsychiatry should be implemented Background Evidence -based practice s design ed for large urban clinics are not necessarily portable into smaller isolated clinics . Implementing practice -based collaborative care for depression in smaller primary care clinics presents unique challenges because it is often not feasible to employ on-site psychiatrists . Objective The purpose of the Telemedicine Enhanced Antidepressant Management ( TEAM ) study was to evaluate a telemedicine-based collaborative care model adapted for small clinics without on-site psychiatrists . Design Matched sites were r and omized to the intervention or usual care . Participants Small VA Community-based outpatient clinics with no on-site psychiatrists , but access to telepsychiatrists . In 2003–2004 , 395 primary care patients with PHQ9 depression severity scores ≥12 were enrolled , and followed for 12 months . Patients with serious mental illness and current substance dependence were excluded . Measures Medication adherence , treatment response , remission , health status , health-related quality of life , and treatment satisfaction . Results The sample comprised mostly elderly , white , males with substantial physical and behavioral health comorbidity . At baseline , subjects had moderate depression severity ( Hopkins Symptom Checklist , SCL-20 = 1.8 ) , 3.7 prior depression episodes , and 67 % had received prior depression treatment . Multivariate analyses indicated that intervention patients were more likely to be adherent at both 6 ( odds ratio [ OR ] = 2.1 , p = .04 ) and 12 months ( OR = 2.7 , p = .01 ) . Intervention patients were more likely to respond by 6 months ( OR = 2.0 , p = .02 ) , and remit by 12 months ( OR = 2.4 , p = .02 ) . Intervention patients reported larger gains in mental health status and health-related quality of life , and reported higher satisfaction . Conclusions Collaborative care can be successfully adapted for primary care clinics without on-site psychiatrists using telemedicine technologies BACKGROUND Mental illness has become a significant worldwide health issue in recent years . There is presently insufficient evidence to definitively determine the clinical effectiveness and cost-effectiveness of different health care models . The objective of this study was to evaluate the effectiveness of videoconferencing in mental illness . DATA SOURCES Literature search es were performed in Medline , EMBASE , PsycINFO , Centre for Review s and Dissemination , and The Cochrane Library Controlled Trial Registry data bases ( 1997-May 2008 ) . A search of the following terms was used : e-health , mental disorders ( MeSH term ) , mental health ( MeSH term ) , mental health services ( MeSH term ) , telecare , teleconsultation , telehome , telemedical , telemedicine , telemental , telepsychiatric , telepsychiatry , televideo , videoconference , and videophone . STUDY SELECTION Type of disease , interventions , and clinical outcomes or patient satisfaction were identified . Exclusion criteria included studies that did not analyze intervention outcomes and studies with a sample size of fewer than 10 cases . Peer review and quality assessment according to Cochrane recommendations were required for inclusion . DATA EXTRACTION / SYNTHESIS Of 620 identified articles , 10 r and omized controlled trials are included ( 1,054 patients with various mental disorders ) . There were no statistically significant differences between study groups for symptoms , quality of life , and patient satisfaction . CONCLUSIONS There is insufficient scientific evidence regarding the effectiveness of telepsychiatry in the management of mental illness , and more research is needed to further evaluate its efficiency . However , there is a strong hypothesis that videoconference-based treatment obtains the same results as face-to-face therapy and that telepsychiatry is a useful alternative when face-to-face therapy is not possible Therapist adherence to a manualized cognitive-behavioral anger management group treatment ( AMT ) was compared between therapy delivered via videoconference ( VC ) and the traditional in-person modality , using data from a large , r and omized controlled trial comparing the effectiveness of AMT for veterans with combat-related posttraumatic stress disorder . Therapist adherence was rated for the presence or absence of process and content treatment elements . Secondary analyses were conducted using a repeated measures ANOVA . Overall adherence to the protocol was excellent ( M = 96 % , SD = 1 % ) . Findings indicate that therapist adherence to AMT is similar across delivery modalities and VC is a viable service delivery strategy that does not compromise a therapist 's ability to effectively structure sessions and manage patient care We compared the efficacy of telepsychiatry and same-room treatment of combat-related post-traumatic stress disorder ( PTSD ) using cognitive behavioural therapy in 14 weekly , 90-min treatment sessions . Of 97 patients referred for study participation , 38 were r and omized ( 17 into telepsychiatry , 21 into same-room ) , and approximately 25 ( the number differed by instrument ) had at least one post-baseline assessment . Measures of clinical and process outcomes were examined . No group differences were found on clinical outcomes at three-month follow-up . Satisfaction with treatment ratings was similar in both groups , with ' strong satisfaction ' indicated by veterans in both modalities . Attendance and drop-out were similar in the two groups . The same-room group reported more comfort in talking with their therapist at post-treatment and had better treatment adherence . The results provide preliminary support for the use of telepsychiatry in the treatment of PTSD to improve access to care Little is known about whether the recommendations made during telepsychiatry are actually implemented . We review ed 100 telepsychiatry consultations , chosen r and omly from a paediatric telepsychiatry programme serving rural communities in Ontario . Treatment recommendations had been made for each case review ed and up to nine recommendations had been made for a single case . Twenty-seven percent of recommendations revolved around monitoring ( 10 % ) , changing ( 9 % ) , starting ( 4 % ) , continuing ( 3 % ) and stopping ( 1 % ) medication . Case managers associated with 54 of the cases were interviewed to determine whether the recommendations had been implemented and to examine the barriers and facilitators to implementation . The results indicated that cooperation of both child and parent , clear communication of recommendations , involvement of the school and local health providers , stability of the agencies and availability of services were key components in the successful implementation of recommendations . The matter of technology or technological difficulties acting as a barrier to telepsychiatric consultations was not mentioned by case managers , suggesting that it was not a problem We used a PC-based videoconferencing system to conduct child psychiatry assessment s. The telecommunications link was six digital lines , giving a total b and width of 336 kbit s. Twenty-three patients aged 4 - 16 years , accompanied by their parents , completed two psychiatric assessment s , one via videoconferencing and another face to face FTF . The order of assessment s was r and omized . Question naires were used to record the diagnosis , treatment recommendations and the psychiatrists ' , patients ' and their parents ' satisfaction with each assessment . An independent evaluator concluded that in 22 cases 96 the diagnosis and treatment recommendations made via the videoconferencing system were the same as those made FTF . The psychiatrists stated that videoconferencing assessment s were an adequate alternative to FTF assessment s and did not interfere with diagnosis . However , the responses from the psychiatrist satisfaction question naire showed that they preferred FTF assessment s. No significant difference was found in the patients ' or parents ' satisfaction responses after the two types of assessment . The majority of children 82 liked ' using the telepsychiatry system and six 26 preferred it to a FTF assessment . Most parents 91 indicated that they would prefer to use the videoconferencing system than to travel a long distance to see a psychiatrist in person To investigate whether forensic evaluations can be performed reliably using telemedicine , we compared the results on a st and ard competency assessment instrument using telemedicine ( TM ) and live interviews ( LI ) . Two board-certified forensic psychiatrists used the Georgia Court Competency Test ( GCCT ) to evaluate 21 forensic psychiatric in patients . Half of the patients were r and omly assigned to a telemedicine interview and half were assigned to a live interview . Total scores on the GCCT were similar for both raters , indicating high levels of agreement between telemedicine and live interviews . Patient and provider satisfaction were measured and indicated that , although patients did not express a preference for a particular interview modality , providers reported greater satisfaction with live interviews . Findings suggest that one aspect of competency to st and trial can be reliably evaluated using telemedicine and that patients perceive telemedicine as an acceptable alternative to a st and ard live interview . The limited sample size precludes definite conclusions and further studies involving a larger forensic study population are warranted OBJECTIVE A major problem in the delivery of mental health services is the lack of availability of empirically supported treatment , particularly in rural areas . To date no studies have evaluated the administration of an empirically supported manual-based psychotherapy for a psychiatric condition via telemedicine . The aim of this study was to compare the relative efficacy and acceptability of a manual-based cognitive-behavioral therapy ( CBT ) for bulimia nervosa ( BN ) delivered in person to a comparable therapy delivered via telemedicine . METHOD One hundred twenty-eight adults meeting DSM-IV criteria for BN or eating disorder-not otherwise specified with binge eating or purging at least once per week were recruited through referrals from clinicians and media advertisements in the targeted geographical areas . Participants were r and omly assigned to receive 20 sessions of manual-based , CBT for BN over 16 weeks delivered either face-to-face ( FTF-CBT ) or via telemedicine ( TV-CBT ) by trained therapists . The primary outcome measures were binge eating and purging frequency as assessed by interview at the end of treatment , and again at 3- and 12-month follow-ups . Secondary outcome measures included other bulimic symptoms and changes in mood . RESULTS Retention in treatment was comparable for TV-CBT and FTF-CBT . Abstinence rates at end-of-treatment were generally slightly higher for FTF-CBT compared with TV-CBT , but differences were not statistically significant . FTF-CBT patients also experienced significantly greater reductions in eating disordered cognitions and interview-assessed depression . However , the differences overall were few in number and of marginal clinical significance . CONCLUSIONS CBT for BN delivered via telemedicine was both acceptable to participants and roughly equivalent in outcome to therapy delivered in person Background Older adults who live in rural areas experience significant disparities in health status and access to mental health care . " Telepsychology , " ( also referred to as " telepsychiatry , " or " telemental health " ) represents a potential strategy towards addressing this longst and ing problem . Older adults may benefit from telepsychology due to its : ( 1 ) utility to address existing problematic access to care for rural residents ; ( 2 ) capacity to reduce stigma associated with traditional mental health care ; and ( 3 ) utility to overcome significant age-related problems in ambulation and transportation . Moreover , preliminary evidence indicates that telepsychiatry programs are often less expensive for patients , and reduce travel time , travel costs , and time off from work . Thus , telepsychology may provide a cost-efficient solution to access-to-care problems in rural areas . Methods We describe an ongoing four-year prospect i ve , r and omized clinical trial comparing the effectiveness of an empirically supported treatment for major depressive disorder , Behavioral Activation , delivered either via in-home videoconferencing technology ( " Telepsychology " ) or traditional face-to-face services ( " Same-Room " ) . Our hypothesis is that in-homeTelepsychology service delivery will be equally effective as the traditional mode ( Same-Room ) . Two-hundred twenty-four ( 224 ) male and female elderly participants will be administered protocol -driven individual Behavioral Activation therapy for depression over an 8-week period ; and subjects will be followed for 12-months to ascertain longer-term effects of the treatment on three outcomes domains : ( 1 ) clinical outcomes ( symptom severity , social functioning ) ; ( 2 ) process variables ( patient satisfaction , treatment credibility , attendance , adherence , dropout ) ; and ( 3 ) economic outcomes ( cost and re source use ) . Discussion Results from the proposed study will provide important insight into whether telepsychology service delivery is as effective as the traditional mode of service delivery , defined in terms of clinical , process , and economic outcomes , for elderly patients with depression residing in rural areas without adequate access to mental health services . Trial registration National Institutes of Health Clinical Trials Registry ( Clinical Trials.gov identifier # NCT0 Output:	Despite the method ological limitations and heterogeneity of the systematic review s , there appears to be good evidence of effectiveness ( reliability and improved outcomes ) and feasibility ( use , satisfaction , acceptability and cost ) for videoconference-based telepsychiatry internationally .
MS21318	*TASK* the task is to summarize an input biomedical literature in six sentences *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 : Several studies have evaluated whether evidence -based medicine ( EBM ) training courses can improve skills such as literature search ing and critical appraisal but to date , few data exist on whether teaching EBM skills and providing evidence -based re sources result in change in behavior or clinical outcomes . This study was conducted to evaluate whether a multifaceted EBM intervention consisting of teaching EBM skills and provision of electronic evidence re sources changed clinical practice . DESIGN : Before/after study . SETTING : The medical inpatient units at a district general hospital . PARTICIPANTS : Thirty-five attending physicians and 12 medicine residents . INTERVENTION : A multicomponent EBM intervention was provided including an EBM training course of seven 1-hour sessions , an EBM syllabus and textbook , and provision of evidence -based re sources on the hospital network . MEASUREMENTS AND MAIN RESULTS : The primary outcome of the study was the quality of evidence in support of therapies initiated for the primary diagnoses in 483 consecutive patients admitted during the month before and the month after the intervention . Patients admitted after implementation of the EBM intervention were significantly more likely to receive therapies proven to be beneficial in r and omized controlled trials ( 62 % vs 49 % ; P=.016 ) . Of these trial-proven therapies , those offered after the EBM intervention were significantly more likely to be based on high- quality r and omized controlled trials ( 95 % vs 87 % ; P=.023 ) . CONCLUSIONS : A multifaceted intervention design ed to teach and support EBM significantly improved evidence -based practice patterns in a district general hospital Abstract OBJECTIVE : To determine if a simple educational intervention can increase resident physician literature search activity . DESIGN : R and omized controlled trial . SETTING : University hospital-based internal medicine training program . PATIENTS / PARTICIPANTS : Forty-eight medical residents rotating on the general internal medicine service . INTERVENTIONS : One-hour didactic session , the use of well-built clinical question cards , and practical sessions in clinical question building . MEASUREMENTS AND MAIN RESULTS : Objective data from the library information system that included the number of log-ons to MEDLINE , search ing volume , abstract s viewed , full-text articles viewed , and time spent search ing . Median search activity as measured per person per week ( control vs intervention ) : number of log-ons to MEDLINE ( 2.1 vs 4.4 , P<.001 ) ; total number of search sets ( 24.0 vs 74.2 , P<.001 ) ; abstract s viewed ( 5.8 vs 17.7 , P=.001 ) ; articles viewed ( 1.0 vs 2.6 , P=.005 ) ; and hours spent search ing ( 0.8 vs 2.4 , P<.001 ) . CONCLUSIONS : A simple educational intervention can markedly increase resident search ing activity Background Previous studies have shown that Norwegian public health physicians do not systematic ally and explicitly use scientific evidence in their practice . They work in an environment that does not encourage the integration of this information in decision-making . In this study we investigate whether a theoretically grounded tailored intervention to diffuse evidence -based public health practice increases the physicians ' use of research information . Methods 148 self-selected public health physicians were r and omised to an intervention group ( n = 73 ) and a control group ( n = 75 ) . The intervention group received a multifaceted intervention while the control group received a letter declaring that they had access to library services . Baseline assessment s before the intervention and post-testing immediately at the end of a 1.5-year intervention period were conducted . The intervention was theoretically based and consisted of a workshop in evidence -based public health , a newsletter , access to a specially design ed information service , to relevant data bases , and to an electronic discussion list . The main outcome measure was behaviour as measured by the use of research in different documents . Results The intervention did not demonstrate any evidence of effects on the objective behaviour outcomes . We found , however , a statistical significant difference between the two groups for both knowledge scores : Mean difference of 0.4 ( 95 % CI : 0.2–0.6 ) in the score for knowledge about EBM-re sources and mean difference of 0.2 ( 95 % CI : 0.0–0.3 ) in the score for conceptual knowledge of importance for critical appraisal . There were no statistical significant differences in attitude- , self-efficacy- , decision-to-adopt- or job-satisfaction scales . There were no significant differences in Cochrane library search ing after controlling for baseline values and characteristics . Conclusion Though demonstrating effect on knowledge the study failed to provide support for the hypothesis that a theory-based multifaceted intervention targeted at identified barriers will change professional behaviour BACKGROUND AND OBJECTIVES Medical education experts have called for improved training in evidence -based medicine ( EBM ) and the increased use of e-learning technologies in medical education . In response , we developed an interactive , Web-based curriculum on key aspects of EBM in family medicine . METHODS Students participating in a 6-week family medicine clerkship ( n=238 ) were r and omly assigned to intervention ( n=134 ) or control ( n=104 ) groups . Both groups participated in the traditional clerkship experience , but intervention group students received additional training via an on-line curriculum that included learning modules in MEDLINE search ing skills , EBM skills , and the calculation of the number needed to treat ( NNT ) statistic . The on-line curriculum was evaluated using a case-control design with a test case at the clerkship 's end . RESULTS Results suggested that the on-line curriculum was effective , with experimental group students outperforming control group participants on a variety of measures , including the number of MEDLINE search es conducted during the clerkship ( 13 search es versus 3 search es ) and the quality of literature search strategies on an evaluation patient case study ( 2.9 versus 2.1 on a 1=poor to 4=excellent scale ) . Intervention group students reported greater confidence and enjoyment in search ing the biomedical journal literature via MEDLINE and were more likely to identify the best articles ( r and omized controlled trials or meta-analyses ) for the evaluation case from among those retrieved ( 60 % versus 34 % ) . In addition , intervention group students ' abilities to correctly calculate the NNT were significantly higher than those of control group participants ( 73 % versus 27 % ) . Intervention group students were more likely than control subjects to report learning from other students during the clerkship . CONCLUSIONS This study demonstrates that an e-learning approach to educating medical students to effectively search MEDLINE for articles meeting the criteria for evidence -based practice can result in higher- quality literature search strategies , identification of higher- quality evidence , and improved confidence in information retrieval and analysis skills OBJECTIVE To determine if a preceptor and individualized feedback improves the performance of physicians in search ing MEDLINE in clinical setting s. DESIGN R and omized controlled trial with 2 to 10 months follow-up . SETTING A 300-bed teaching hospital . PARTICIPANTS All 392 physicians and physicians-in-training from 6 major clinical departments were invited to participate if they made patient-care decisions during the study period ; 79.4 % agreed . INTERVENTIONS All participants were given 2 hours of basic training , then r and omized to a control group ( no further intervention ) or an intervention group in which each person chose a clinical preceptor experienced in MEDLINE search ing and received individualized feedback from a study librarian on each of their 1st 10 search es . MAIN OUTCOME MEASURES The number and proportion of relevant and irrelevant references retrieved for 1st , 4th , and 8th search es of participants were compared with independent librarian search es on the same topics . RESULTS Intervention group members did not search more often than controls ( 5.9 search es per month versus 4.7 , respectively ; P = 0.26 ) and there were no significant differences in the quality of search es . Rather , search performance for both groups improved , with the average number of relevant references retrieved per search increasing from 4.5 to 7.4 ( P < 0.01 ) . The librarian retrieved more relevant citations than participants for the 1st search ( P = 0.001 ) but not for the 4th ( P = 0.60 ) or 8th ( P = 0.76 ) search es . CONCLUSIONS A program of assigning preceptors and providing feedback on individual search es did not enhance the quantity or quality of search es . Soon after a basic introduction to search ing , however , clinicians in both groups improved their search performance Objective To determine whether fellowship training in critical care medicine with critical appraisal exercises improves the ability and confidence of fellows to evaluate the medical literature . Design Prospect i ve , interventional pilot study . Setting Multidisciplinary critical care medicine training program at a large university hospital . InterventionFellows were given three didactic sessions covering study design , analysis , and critical appraisal techniques . During the course of the year , each fellow was required to review one article from the literature and present a critique of this article to the group and faculty ( Journal Club ) . Fellows were guided in the preparation of this presentation by one of the critical care medicine faculty . Finally , a written analysis and critique of the article was performed by each fellow . Measurements and Main Results A test was given to each fellow at the beginning and end of the academic year . This test consisted of two pairs of articles on therapy for acute lung injury . For the pretest , each fellow was assigned , at r and om , one pair of articles . Fellows were given 1 hr to review both articles and to fill out a six-point test to assess their ability and confidence to appraise each article . At the end of the year , each fellow was tested on the opposite pair , the tests were grade d in a blinded fashion and the results of each test were compared . Six fellows completed both pre- and posttests . These paired results were analyzed separately , whereas results for another six fellows were conducted as an unpaired analysis . Mean scores increased both for the paired analysis ( 4.1 ± 0.7 vs. 5.1 ± 0.5;p = .015 ) and for the unpaired analysis ( 4.3 ± 0.6 vs. 5.0 ± 0.5;p = .012 ) . Self-reported confidence in critical appraisal also increased ( 2.5 ± 0.5 vs. 3.9 ± 0.7;p = .004 and 2.6 ± 0.5 vs. 3.9 ± 0.6;p < .001 , respectively ) . Conclusion Critical appraisal exercises used in the training of critical care medicine fellows appear to improve both ability and confidence to appraise relevant medical literature Introduction Critical appraisal skills are believed to play a central role in an evidence -based approach to health practice . The aim of this study was to evaluate the effectiveness and costs of a critical appraisal skills educational intervention aim ed at health care professionals . Methods This prospect i ve controlled trial r and omized 145 self-selected general practitioners , hospital physicians , professions allied to medicine , and healthcare managers/administrators from the South West of Engl and to a half-day critical appraisal skills training workshop ( based on the model of problem-based small group learning ) or waiting list control . The following outcomes were assessed at 6-months follow up : knowledge of the principles necessary for appraising evidence ; attitudes towards the use of evidence about healthcare ; evidence seeking behaviour ; perceived confidence in appraising evidence ; and ability to critically appraise a systematic review article . Results At follow up overall knowledge score [ mean difference : 2.6 ( 95 % CI : 0.6 to 4.6 ) ] and ability to appraise the results of a systematic review [ mean difference : 1.2 ( 95 % CI : 0.01 to 2.4 ) ] were higher in the critical skills training group compared to control . No statistical significant differences in overall attitude towards evidence , evidence seeking behaviour , perceived confidence , and other areas of critical appraisal skills ability ( methodology or generalizability ) were observed between groups . Taking into account the workshop provision costs and costs of participants time and expenses of participants , the average cost of providing the critical appraisal workshops was approximately £ 250 per person . Conclusions The findings of this study challenge the policy of funding ' one-off ' educational interventions aim ed at enhancing the evidence -based practice of health care professionals . Future evaluations of evidence -based practice interventions need to take in account this trial 's negative findings and method ological difficulties Background The specificity of clinical questions is gauged by explicit descriptions of four dimensions : subjects , interventions , comparators and outcomes of interest . This study determined whether adding simple instructions and examples on clinical question formulation would increase the specificity of the su bmi tted question compared to using a st and ard form without instructions and examples . Methods A r and omised controlled trial was conducted in an evidence - search and appraisal service . New participants were invited to reformulate clinical queries . The Control Group was given no instructions . The Intervention Group was given a brief explanation of proper formulation , written instructions , and diagrammatic examples . The primary outcome was the change in the proportion of reformulated questions that described each the dimensions of specificity . Results Fifty-two subjects agreed to participate in the trial of which 13 were lost to follow-up . The remaining 17 Intervention Group and 22 Control Group participants were analysed . Baseline characteristics were comparable . Overall , 20 % of initially su bmi tted questions from both groups were properly specified ( defined as an explicit statement describing all dimensions of specificity ) . On follow-up , 7/14 questions previously rated as mis-specified in the Intervention Group had all dimensions described at follow-up ( p = 0.008 ) while the Control Group did not show any changes from baseline . Participants in the Intervention Group were also more likely to explicitly describe patients ( p = 0.028 ) , comparisons ( p = 0.014 ) , and outcomes ( p = 0.008 ) . Conclusions This trial demonstrated the positive impact of specific instructions on the proportion of properly-specified clinical queries . The evaluation of the long-term impact of such changes is an area of continued research A double-blind r and omised controlled trial was conducted on a group of Output:	ConclusionS mall improvements in knowledge , skills , attitudes or behavior are noted when measured alone . A large improvement in skills and knowledge in EBP is noted when measured together in a total test score .
MS21319	*TASK* the task is to summarize an input biomedical literature in six sentences *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 age-specific mortality rates and total deaths from specific cancers have not been documented for the various regions and sub population s of India . We therefore assessed the cause of death in 2001 - 03 in homes in small areas that were chosen to be representative of all the parts of India . METHODS At least 130 trained physicians independently assigned causes to 122,429 deaths , which occurred in 1·1 million homes in 6671 small areas that were r and omly selected to be representative of all of India , based on a structured non-medical surveyor 's field report . FINDINGS 7137 of 122,429 study deaths were due to cancer , corresponding to 556,400 national cancer deaths in India in 2010 . 395,400 ( 71 % ) cancer deaths occurred in people aged 30 - 69 years ( 200,100 men and 195,300 women ) . At 30 - 69 years , the three most common fatal cancers were oral ( including lip and pharynx , 45,800 [ 22·9 % ] ) , stomach ( 25,200 [ 12·6 % ] ) , and lung ( including trachea and larynx , 22,900 [ 11·4 % ] ) in men , and cervical ( 33,400 [ 17·1 % ] ) , stomach ( 27,500 [ 14·1 % ] ) , and breast ( 19,900 [ 10·2 % ] ) in women . Tobacco-related cancers represented 42·0 % ( 84,000 ) of male and 18·3 % ( 35,700 ) of female cancer deaths and there were twice as many deaths from oral cancers as lung cancers . Age-st and ardised cancer mortality rates per 100,000 were similar in rural ( men 95·6 [ 99 % CI 89·6 - 101·7 ] and women 96·6 [ 90·7 - 102·6 ] ) and urban areas ( men 102·4 [ 92·7 - 112·1 ] and women 91·2 [ 81·9 - 100·5 ] ) , but varied greatly between the states , and were two times higher in the least educated than in the most educated adults ( men , illiterate 106·6 [ 97·4 - 115·7 ] vs most educated 45·7 [ 37·8 - 53·6 ] ; women , illiterate 106·7 [ 99·9 - 113·6 ] vs most educated 43·4 [ 30·7 - 56·1 ] ) . Cervical cancer was far less common in Muslim than in Hindu women ( study deaths 24 , age-st and ardised mortality ratio 0·68 [ 0·64 - 0·71 ] vs 340 , 1·06 [ 1·05 - 1·08 ] ) . INTERPRETATION Prevention of tobacco-related and cervical cancers and earlier detection of treatable cancers would reduce cancer deaths in India , particularly in the rural areas that are underserved by cancer services . The substantial variation in cancer rates in India suggests other risk factors or causative agents that remain to be discovered . FUNDING Bill & Melinda Gates Foundation and US National Institutes of Health BACKGROUND National malaria death rates are difficult to assess because reliably diagnosed malaria is likely to be cured , and deaths in the community from undiagnosed malaria could be misattributed in retrospective enquiries to other febrile causes of death , or vice-versa . We aim ed to estimate plausible ranges of malaria mortality in India , the most populous country where the disease remains common . METHODS Full-time non-medical field workers interviewed families or other respondents about each of 122,000 deaths during 2001 - 03 in 6671 r and omly selected areas of India , obtaining a half-page narrative plus answers to specific questions about the severity and course of any fevers . Each field report was sent to two of 130 trained physicians , who independently coded underlying causes , with discrepancies resolved either via anonymous reconciliation or adjudication . FINDINGS Of all coded deaths at ages 1 month to 70 years , 2681 ( 3·6 % ) of 75,342 were attributed to malaria . Of these , 2419 ( 90 % ) were in rural areas and 2311 ( 86 % ) were not in any health-care facility . Death rates attributed to malaria correlated geographically with local malaria transmission ratesderived independently from the Indian malaria control programme . The adjudicated results show 205,000 malaria deaths per year in India before age 70 years ( 55,000 in early childhood , 30,000 at ages 5 - 14 years , 120,000 at ages 15 - 69 years ) ; 1·8 % cumulative probability of death from malaria before age 70 years . Plausible lower and upper bounds ( on the basis of only the initial coding ) were 125,000 - 277,000 . Malaria accounted for a substantial minority of about 1·3 million unattended rural fever deaths attributed to infectious diseases in people younger than 70 years . INTERPRETATION Despite uncertainty as to which unattended febrile deaths are from malaria , even the lower bound greatly exceeds the WHO estimate of only 15,000 malaria deaths per year in India ( 5000 early childhood , 10 000 thereafter ) . This low estimate should be reconsidered , as should the low WHO estimate of adult malaria deaths worldwide . FUNDING US National Institutes of Health , Canadian Institute of Health Research , Li Ka Shing Knowledge Institute Background Physician-coded verbal autopsy ( PCVA ) is the most widely used method to determine causes of death ( CODs ) in countries where medical certification of death is uncommon . Computer-coded verbal autopsy ( CCVA ) methods have been proposed as a faster and cheaper alternative to PCVA , though they have not been widely compared to PCVA or to each other . Methods We compared the performance of open- source r and om forest , open- source tariff method , InterVA-4 , and the King-Lu method to PCVA on five data sets comprising over 24,000 verbal autopsies from low- and middle-income countries . Metrics to assess performance were positive predictive value and partial chance-corrected concordance at the individual level , and cause-specific mortality fraction accuracy and cause-specific mortality fraction error at the population level . Results The positive predictive value for the most probable COD predicted by the four CCVA methods averaged about 43 % to 44 % across the data sets . The average positive predictive value improved for the top three most probable CODs , with greater improvements for open- source r and om forest ( 69 % ) and open- source tariff method ( 68 % ) than for InterVA-4 ( 62 % ) . The average partial chance-corrected concordance for the most probable COD predicted by the open- source r and om forest , open- source tariff method and InterVA-4 were 41 % , 40 % and 41 % , respectively , with better results for the top three most probable CODs . Performance generally improved with larger data sets . At the population level , the King-Lu method had the highest average cause-specific mortality fraction accuracy across all five data sets ( 91 % ) , followed by InterVA-4 ( 72 % across three data sets ) , open- source r and om forest ( 71 % ) and open- source tariff method ( 54 % ) . Conclusions On an individual level , no single method was able to replicate the physician assignment of COD more than about half the time . At the population level , the King-Lu method was the best method to estimate cause-specific mortality fractions , though it does not assign individual CODs . Future testing should focus on combining different computer-coded verbal autopsy tools , paired with PCVA strengths . This includes using open- source tools applied to larger and varied data sets ( especially those including a r and om sample of deaths drawn from the population ) , so as to establish the performance for age- and sex-specific CODs Background Computer-coded verbal autopsy ( CCVA ) is a promising alternative to the st and ard approach of physician-certified verbal autopsy ( PCVA ) , because of its high speed , low cost , and reliability . This study introduces a new CCVA technique and vali date s its performance using defined clinical diagnostic criteria as a gold st and ard for a multisite sample of 12,542 verbal autopsies ( VAs ) . Methods The R and om Forest ( RF ) Method from machine learning ( ML ) was adapted to predict cause of death by training r and om forests to distinguish between each pair of causes , and then combining the results through a novel ranking technique . We assessed quality of the new method at the individual level using chance-corrected concordance and at the population level using cause-specific mortality fraction ( CSMF ) accuracy as well as linear regression . We also compared the quality of RF to PCVA for all of these metrics . We performed this analysis separately for adult , child , and neonatal VAs . We also assessed the variation in performance with and without household recall of health care experience ( HCE ) . Results For all metrics , for all setting s , RF was as good as or better than PCVA , with the exception of a nonsignificantly lower CSMF accuracy for neonates with HCE information . With HCE , the chance-corrected concordance of RF was 3.4 percentage points higher for adults , 3.2 percentage points higher for children , and 1.6 percentage points higher for neonates . The CSMF accuracy was 0.097 higher for adults , 0.097 higher for children , and 0.007 lower for neonates . Without HCE , the chance-corrected concordance of RF was 8.1 percentage points higher than PCVA for adults , 10.2 percentage points higher for children , and 5.9 percentage points higher for neonates . The CSMF accuracy was higher for RF by 0.102 for adults , 0.131 for children , and 0.025 for neonates . Conclusions We found that our RF Method outperformed the PCVA method in terms of chance-corrected concordance and CSMF accuracy for adult and child VA with and without HCE and for neonatal VA without HCE . It is also preferable to PCVA in terms of time and cost . Therefore , we recommend it as the technique of choice for analyzing past and current verbal autopsies Background Physician review of a verbal autopsy ( VA ) and completion of a death certificate remains the most widely used approach for VA analysis . This study provides new evidence about the performance of physician-certified verbal autopsy ( PCVA ) using defined clinical diagnostic criteria as a gold st and ard for a multisite sample of 12,542 VAs . The study was also design ed to analyze issues related to PCVA , such as the impact of a second physician reader on the cause of death assigned , the variation in performance with and without household recall of health care experience ( HCE ) , and the importance of local information for physicians reading VAs . Methods The certification was performed by 24 physicians . The assignment of VA was r and om and blinded . Each VA was certified by one physician . Half of the VAs were review ed by a different physician with household recall of health care experience included . The completed death certificate was processed for automated ICD-10 coding of the underlying cause of death . PCVA was compared to gold st and ard cause of death assignment based on strictly defined clinical diagnostic criteria that are part of the Population Health Metrics Research Consortium ( PHMRC ) gold st and ard verbal autopsy study . Results For individual cause assignment , the overall chance-corrected concordance for PCVA against the gold st and ard cause of death is less than 50 % , with substantial variability by cause and physician . Physicians assign the correct cause around 30 % of the time without HCE , and addition of HCE improves performance in adults to 45 % and slightly higher in children to 48 % . Physicians estimate cause-specific mortality fractions ( CSMFs ) with considerable error for adults , children , and neonates . Only for neonates for a cause list of six causes with HCE is accuracy above 0.7 . In all three age groups , CSMF accuracy improves when household recall of health care experience is available . Conclusions Results show that physician coding for cause of death assignment may not be as robust as previously thought . The time and cost required to initially collect the verbal autopsies must be considered in addition to the analysis , as well as the impact of diverting physicians from servicing immediate health needs in a population to review VAs . All of these considerations highlight the importance and urgency of developing better methods to more reliably analyze past and future verbal autopsies to obtain the highest quality mortality data from population s without reliable death certification Background Verbal autopsy is important for detecting causes of death including HIV in areas with inadequate vital registration systems . Before antiretroviral therapy ( ART ) introduction , a verbal autopsy study in rural Ug and a found that half of adult deaths assessed were in HIV-positive individuals . We used verbal autopsy to compare the proportion of HIV-positive adult deaths in the periods before and after ART introduction . Methods Between 2006 and 2008 , all adult ( ≥ 13 years ) deaths in a prospect i ve population -based cohort study were identified by monthly death registration , and HIV serostatus was determined through annual serosurveys . A clinical officer interviewed a relative of the deceased using a verbal autopsy question naire . Two clinicians independently review ed the question naires and classified the deaths as HIV-positive or not . A third clinician was the tie-breaker in case of nonagreement . The performance of the verbal autopsy tool was assessed using HIV serostatus as the gold st and ard of comparison . We Output:	Sensitivity of PCVA versus hospital-assigned COD varied widely by cause , but showed consistently high specificity . At the population level , the relative CSMF error between PCVA and hospital-based deaths indicated good performance for most CODs . R and om Forest had the best CSMF accuracy performance , followed closely by PCVA and the other CCVA methods , but with lower values for InterVA-3 . Conclusions There is no single best-performing coding method for verbal autopsies across various studies and metrics . There is little current justification for CCVA to replace PCVA , particularly as physician diagnosis remains the worldwide st and ard for clinical diagnosis on live patients .
MS21320	*TASK* the task is to summarize an input biomedical literature in six sentences *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 hospital readmission rate has been proposed as an important outcome indicator computable from routine statistics . However , most commonly used measures raise conceptual issues . Objectives : We sought to evaluate the usefulness of the computerized algorithm for identifying avoidable readmissions on the basis of minimum bias , criterion validity , and measurement precision . Research Design and Subjects : A total of 131,809 hospitalizations of patients discharged alive from 49 hospitals were used to compare the predictive performance of risk adjustment methods . A subset of a r and om sample of 570 medical records of discharge/readmission pairs in 12 hospitals were review ed to estimate the predictive value of the screening of potentially avoidable readmissions . Measures : Potentially avoidable readmissions , defined as readmissions related to a condition of the previous hospitalization and not expected as part of a program of care and occurring within 30 days after the previous discharge , were identified by a computerized algorithm . Unavoidable readmissions were considered as censored events . Results : A total of 5.2 % of hospitalizations were followed by a potentially avoidable readmission , 17 % of them in a different hospital . The predictive value of the screen was 78 % ; 27 % of screened readmissions were judged clearly avoidable . The correlation between the hospital rate of clearly avoidable readmission and all readmissions rate , potentially avoidable readmissions rate or the ratio of observed to expected readmissions were respectively 0.42 , 0.56 and 0.66 . Adjustment models using clinical information performed better . Conclusion : Adjusted rates of potentially avoidable readmissions are scientifically sound enough to warrant their inclusion in hospital quality surveillance BACKGROUND the usefulness of geriatric evaluation and management ( GEM ) approaches in the care of frail elderly patients remains uncertain . We examined whether an inpatient geriatric consultation service might be beneficial in a country with a social welfare system . METHODS we conducted a r and omised trial with 345 patients from five centres . Ninety additional patients from four separate centres without GEM teams served as an external comparison . All patients were hospitalised , at least 65 years and frail . Patients were r and omly assigned to either comprehensive geriatric assessment and management in the form of consultations and follow-up or usual care . Primary outcomes were rehospitalisation and nursing home placement 1 year after r and omisation . Secondary outcomes were survival , functional , emotional and cognitive status , social situation and quality of life . FINDINGS at 12 months , the groups did not differ in the rate of rehospitalisation ( intervention 67 % , control 60 % , P=0.30 ) , nursing home placement ( intervention 19 % , control 14 % , P=0.27 ) , survival ( intervention 81 % , control 85 % , P=0.56 ) or any of the other secondary measures . The external comparison groups were also similar in nursing home placement ( 16 % , P=0.40 ) , survival ( 80 % , P=0.88 ) and all the secondary variables , but rehospitalisation was less ( 48 % , P=0.04 ) . No subgroup benefited from the intervention . INTERPRETATION care provided by consultation teams did not improve the rates of rehospitalisation or nursing home placement . This is not due to carry-over effects of geriatric knowledge into the control group Research is needed to help identify interventions that will improve the capacity or functioning of health systems and thereby contribute to achieving global health goals . Well conducted , r and omized controlled trials ( RCTs ) , insofar as they reduce bias and confounding , provide the strongest evidence for identifying which interventions delivered directly to individuals are safe and effective . When ethically feasible , they can also help reduce bias and confounding when assessing interventions targeting entire health systems . However , additional challenges emerge when research focuses on interventions that target the multiple units of organization found within health systems . Hence , one can not complacently assume that r and omization can reduce or eliminate bias and confounding to the same degree in every instance . While others have articulated arguments in favour of alternative design s , this paper is intended to help people underst and why the potential value afforded by RCTs may be threatened . Specifically , it suggests six points to be borne in mind when exploring the challenges entailed in design ing or evaluating RCTs on health system interventions : ( i ) the number of units available for r and omization ; ( ii ) the complexity of the organizational unit under study ; ( iii ) the complexity of the intervention ; ( iv ) the complexity of the cause-effect pathway , ( v ) contamination ; and ( vi ) outcome heterogeneity . The authors suggest that the latter may be informative and that the reasons behind it should be explored and not ignored . Based on improved underst and ing of the value and possible limitations of RCTs on health system interventions , the authors show why we need broader platforms of research to complement RCTs OBJECTIVES To evaluate an interdisciplinary intervention program for older people with hip fracture in Taiwan . DESIGN R and omized experimental design . SETTING A 3,800-bed medical center in northern Taiwan . PARTICIPANTS Elderly patients with hip fracture ( N=137 ) were r and omly assigned to an experimental ( n=68 ) or control ( n=69 ) group . INTERVENTION An interdisciplinary program of geriatric consultation , continuous rehabilitation , and discharge planning . MEASUREMENTS Demographic and outcome variables were measured . Outcome variables included service utilization , clinical outcomes , self-care abilities , health-related quality -of-life ( HRQOL ) outcomes , and depressive symptoms . RESULTS Subjects in the experimental group improved significantly more than those in the control group in the following outcomes : ratio of hip flexion 1 month after discharge ( P=.02 ) , recovery of previous walking ability at 1 month ( P=.04 ) and 3 months ( P=.001 ) after discharge , and activities of daily living at 1 month ( P=.01 ) and 2 months ( P=.001 ) after discharge . Three months after discharge , the experimental group showed significant improvement in peak force of the fractured limb 's quadriceps ( P=.04 ) and the following health outcomes : bodily pain ( P=.03 ) , vitality ( P<.001 ) , mental health ( P=.02 ) , physical function ( P<.001 ) , and role physical ( P=.006 ) . They also had fewer depressive symptoms ( P=.008 ) 3 months after discharge . CONCLUSION This intervention program may benefit older people with hip fractures in Taiwan by improving their clinical outcomes , self-care abilities , and HRQOL and by decreasing depressive symptoms within 3 months after discharge OBJECTIVE To test the impact of a geriatric evaluation and management model on the costs of acute hospital management of emergently admitted older adults . DESIGN R and omized controlled trial . Patients were followed in the acute hospital from admission through discharge . Results based on both univariate and multiple regression analyses . SETTING Private , nonprofit , academic medical center in a densely populated urban area . PATIENTS Adults 70 years of age and older admitted from the Emergency Department to the medicine service ( non-ICU admission ) who did not have an internist on staff at the admitting hospital . Of 141 r and omized patients , 111 ( 78.7 % ) met eligibility criteria . INTERVENTION Assignment of a geriatrician and a social worker as the primary managing team during the hospital stay . MAIN OUTCOME MEASURES Length of stay , total cost of acute hospital care , cost of laboratory , pharmacy , and rehabilitation services . RESULTS Patients in the intervention group had 2.1 fewer days of hospitalization , but this shorter length of stay was not statistically significant ( P = 0.108 ) . There were no differences in mortality or discharge disposition . In risk-adjusted , multiple regression analysis the intervention group had a statistically significant lower predicted total cost per patient than the usual care group ( -$2,544 , P = 0.029 ) ; assignment to the intervention group was associated with a lower predicted cost per patient for laboratory ( including cardiology graphics ) services ( P = 0.007 ) and pharmacy costs ( P = 0.047 ) . CONCLUSIONS When controlled for important predictors of expected re source use , care provided by a geriatric management team result ed in a significant reduction in the cost of hospitalization . A reduction in the cost of laboratory , cardiographic , and pharmacy services is consistent with the team 's philosophy of defining the services needed based on goals related to functional outcomes OBJECTIVES To develop a self-report screening tool to identify older people in the emergency department ( ED ) of a hospital at increased risk of adverse health outcomes , including : death , admission to a nursing home or long-term hospitalization , or a clinical ly significant decrease in functional status . DESIGN Prospect i ve ( 6-month ) follow-up study of a cohort of ED patients aged 65 and older . SETTING The EDs of four acute-care hospitals in Montreal , Quebec , Canada . PARTICIPANTS Community-dwelling patients aged 65 and older who came to the EDs during the weekday shift over a 3-month recruitment period . Patients were excluded if they could not be interviewed either because of their medical condition or because of cognitive impairment and no other informant was available . MEASUREMENTS Measures ascertained at the ED visit included : 27 self-report screening questions on social , physical , and mental risk factors ; medical history ; use of hospital services , medications , and alcohol ; and the Older American Re sources and Services ( OARS ) activities of daily living ( ADL ) scale . At follow-up , the OARS scale was readministered by telephone , and other adverse health outcomes were ascertained . RESULTS Among 1673 patients who completed the follow-up measures , 488 ( 29.2 % ) had an adverse health outcome . Scale development and selection methods included logistic regression , receiver operating characteristic curves , and expert judgment . The proposed screening tool ( ISAR ) comprises six self-report questions on functional dependence ( premorbid and acute change ) , recent hospitalization , impaired memory and vision , and polymedication . The tool performed well in the total cohort aged 65 and older , and in sub-groups defined by disposition ( admitted or released from ED ) , language of question naire administration ( French or English ) , information source ( patient or other ) , and other characteristics . CONCLUSIONS The ISAR is a short self-report question naire that can quickly identify older patients in the ED at increased risk of several adverse health outcomes and those with current disability OBJECTIVES To evaluate whether an early multidisciplinary geriatric intervention in elderly patients with hip fracture reduced length of stay , morbidity , and mortality and improved functional evolution . DESIGN R and omized , controlled intervention trial . SETTING Orthopedic ward in a university hospital . PARTICIPANTS Three hundred nineteen patients aged 65 and older hospitalized for hip fracture surgery . INTERVENTION Participants were r and omly assigned to a daily multidisciplinary geriatric intervention ( n=155 ) or usual care ( n=164 ) during hospitalization in the acute phase of hip fracture . MEASUREMENTS Primary endpoints were in-hospital length of stay and incidence of death or major medical complications . Secondary endpoints were the rate of recovery of previous activities of daily living and ambulation ability at 3 , 6 , and 12 months . RESULTS Median length of stay was 16 days in the geriatric intervention group and 18 days in the usual care group ( P=.06 ) . Patients assigned to the geriatric intervention showed a lower in-hospital mortality ( 0.6 % vs 5.8 % , P=.03 ) and major medical complications rate ( 45.2 % vs 61.7 % , P=.003 ) . After adjustment for confounding variables , geriatric intervention was associated with a 45 % lower probability of death or major complications ( 95 % confidence interval=7 - 68 % ) . More patients in the geriatric intervention group achieved a partial recovery at 3 months ( 57 % vs 44 % , P=.03 ) , but there were no differences between the groups at 6 and 12 months . CONCLUSION Early multidisciplinary daily geriatric care reduces in-hospital mortality and medical complications in elderly patients with hip fracture , but there is not a significant effect on length of hospital stay or long-term functional recovery Background and aims : Older hospitalized patients are at risk of functional decline , which is associated with several negative outcomes . The aim of this study was to compare the predictive accuracy of the Identification of Seniors At Risk ( ISAR ) , Variable Indicative for Placement risk ( VIP ) and the Flemish version of the Triage Risk Screening Tool ( TRST ) in predicting functional decline . Methods : A prospect i ve cohort study with 30 days follow-up in geriatric , medical and surgical wards in 25 hospitals was conducted . 752 participants aged 75 years or older were eligible for inclusion . Baseline data were gathered within 72 hours of admission . Functional decline was defined as an increase of one point or more from the premorbid Katz score to the score 30 days post-discharge . Positive predictive value ( PPV ) and negative predictive value ( NPV ) were calculated on 2 × 2 tables as well as by Bayes ’ theorem . Results : Functional decline at 30 days postdischarge was observed in 279 participants ( 39 % ) . ISAR and Flemish TRST showed high sensitivity ( 88%–78 % ) and fair NPV ( 62%–67 % ) , but low specificity ( 19%–30 % ) and low PPV ( 47%–48 % ) using the original cut-off of ≥2 . The sensitivity of VIP with cut-off ≥2 was too low ( 62 % ) , but could be optimized with cut-off ≥1 , showing sensitivity , specificity , PPV and NPV of 8 Output:	Results The individual studies show that an inpatient geriatric consultation team intervention has favorable effects on functional status , readmission and mortality rate . None of the studies found an effect on the length of the hospital stay . Conclusions Inpatient geriatric consultation team interventions have a significant impact on mortality rate at 6 and 8 months postdischarge , but have no significant impact on functional status , readmission or length of stay . The reason for the lack of effect on these latter outcomes may be due to insufficient statistical power or the insensitivity of the measuring method for , for example , functional status .
MS21321	*TASK* the task is to summarize an input biomedical literature in six sentences *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 present the 3-year outcomes of a double-blind , multicenter , r and omized trial comparing vaginal prolapse repair with and without mesh . METHODS : This was a planned final analysis of women with Pelvic Organ Prolapse Quantification ( POP-Q ) stage 2–4 prolapse r and omized to traditional vaginal prolapse surgery without mesh and vaginal colpopexy repair with mesh . We evaluated anatomic , symptomatic , and combined cure rates for those with at least 3-year vali date d quality -of-life question naires and 2- or 3-year postoperative blinded POP-Q examination . Participants undergoing reoperation for recurrent prolapse were removed for anatomic and subjective outcomes analysis and considered failures for combined outcomes analysis . RESULTS : Sixty-five women were enrolled ( 33 mesh , 32 no mesh ) before the study was prematurely halted as a result of a 15.6 % mesh exposure rate . At 3 years , 51 of 65 ( 78 % ) had quality -of-life question naires ( 25 mesh , 26 no mesh ) and 41 ( 63 % ) had examinations . Three participants died , three required reoperation for recurrent prolapse ( all in mesh group ) , and eight were lost to follow-up . No differences were observed between groups at 3 years for prolapse stage or individual prolapse points . Stage improved for each group ( 90 % and 86 % ) from baseline to 3 years ( P<.01 ) . Symptomatic improvement was observed with no differences in scores between groups . Cure rates did not differ between groups using a variety of definitions , and anatomic cure was lowest for the anterior compartment . CONCLUSION : There was no difference in 3-year cure rates when comparing patients undergoing traditional vaginal prolapse surgery without mesh with those undergoing vaginal colpopexy repair with mesh . CLINICAL TRIAL REGISTRATION : Clinical trials.gov , www . clinical trials.gov , NCT00475540 . LEVEL OF EVIDENCE : 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 AIMS To compare efficacy and safety of the traditional colporraphy and transvaginal polypropylene mesh for the treatment of advanced anterior vaginal prolapse according to different success criteria in two-year follow-up . METHODS In this r and omized controlled trial , women with anterior prolapse stage II or greater , with Ba point ≥ + 1 ( POP-Q quantification ) , were r and omly assigned to have either anterior colporraphy ( n = 43 ) or transvaginal mesh repair ( n = 43 ) . The primary outcome was to compare objective success rate under two success definitions : prolapse stage I ( Ba < -1 ) and stage II ( Ba < 0 ) . Secondary outcomes included complications and prolapse symptoms , satisfaction and quality of life ( QoL ) . Intention to treat was used for the primary endpoint and per protocol analysis for the secondary outcomes . RESULTS The groups presented similar preoperative data . Thirty three patients from the colporraphy and 37 from the mesh groups completed two-year follow-up . Under Ba < -1 definition , success rate was 39.53 % for both groups ( P = 1.00 ) . Considering success as Ba < 0 , analysis favored the mesh group by 23 % ( 51.16 % and 74.42 % ; 95 % CI for difference : 3 - 43 % ; P = 0.022 ) . Patients from the mesh group were more satisfied after two years ( 81.8 % and 97.3 % for colporraphy and mesh , respectively , 15.5 % difference ; 95 % CI for difference 1 - 29 % ; P = 0.032 ) . Both procedures similarly improved women 's symptoms and QoL. Some complications were observed , one being a 13.5 % mesh exposure rate . CONCLUSIONS Transvaginal synthetic mesh repair for advanced anterior vaginal prolapse provided higher anatomical success and satisfaction rates compared with traditional colporraphy . Both procedures equally improved quality of life . Neurourol . Urodynam . 35:509 - 514 , 2016 . © 2015 Wiley Periodicals , Introduction and hypothesisEstimation on prevalence and distribution of pelvic organ prolapse ( POP ) signs in a general female population is difficult . We therefore developed and vali date d a prediction model and prognostic instrument . Methods Question naires were sent to a general female population ( 45–85 years ) . A r and om sample underwent vaginal examination for POP ( POPQ ) . A prediction model was developed using multivariate analysis and vali date d in a subgroup of participants . Results Positive question naire-response rate was 46.8 % ( 1,397 of 2,979 ) . From the question naire group , 649 women were vaginally examined ( 46.5 % ) . Prevalence of clinical ly relevant POP was 21 % . Multivariate analysis demonstrated significantly higher odds ratios on the report of vaginal bulging , parity ≥2 and a mother with POP . The receiver operating characteristic curve showed areas under the curve of 0.672 and 0.640 . Conclusions The prevalence of POP at or beyond the hymen could be estimated in a general female population using our prediction model with 17 questions and our POP score chart with eight questions Objective To compare the effects of vaginal hysterectomy ( combined with anterior and /or posterior colporraphy ) and abdominal sacro‐colpopexy ( with preservation of the uterus ) on urogenital function OBJECTIVE To compare the efficacy of two st and ard surgical procedures for post-hysterectomy vaginal vault prolapse in patients with levator ani avulsion . METHODS This was a single-center , r and omized interventional trial , of two st and ard surgical procedures for post-hysterectomy vaginal vault prolapse : Prolift Total vs unilateral vaginal sacrospinous colpopexy with native tissue vaginal repair ( sacrospinous fixation , SSF ) , during the period from 2008 to 2011 . Entry criteria included at least two-compartment prolapse , as well as complete unilateral or bilateral levator ani avulsion injury . The primary outcome was anatomical failure based on clinical and ultrasound assessment . Failure was defined clinical ly , according to the Pelvic Organ Prolapse Quantification system , as Ba , C or Bp at the hymen or below , and on translabial ultrasound as bladder descent to 10 mm or more below the lower margin of the symphysis pubis on maximum Valsalva maneuver . Secondary outcomes were evaluation of continence , sexual function and prolapse symptoms based on vali date d question naires . RESULTS During the study period , 142 patients who were post-hysterectomy underwent surgery for prolapse in our unit ; 72 of these were diagnosed with an avulsion injury and were offered participation in the study . Seventy patients were r and omized into two groups : 36 in the Prolift group and 34 in the SSF group . On clinical examination at 1-year follow-up , we observed one ( 3 % ) case of anatomical failure in the Prolift group and 22 ( 65 % ) in the SSF group ( P < 0.001 ) . Using ultrasound criteria , there was one ( 2.8 % ) failure in the Prolift group compared with 21 ( 61.8 % ) in the SSF group ( P < 0.001 ) . The postoperative POPDI ( Pelvic Organ Prolapse Distress Inventory ) score for subjective outcome was 15.3 in the Prolift group vs 21.7 in the SSF group ( P = 0.16 ) . CONCLUSION In patients with prolapse after hysterectomy and levator ani avulsion injury , SSF has a higher anatomical failure rate than does the Prolift Total procedure at 1-year follow-up BACKGROUND The use of st and ardized mesh kits for repair of pelvic-organ prolapse has spread rapidly in recent years , but it is unclear whether this approach results in better outcomes than traditional colporrhaphy . METHODS In this multicenter , parallel-group , r and omized , controlled trial , we compared the use of a trocar-guided , transvaginal polypropylene-mesh repair kit with traditional colporrhaphy in women with prolapse of the anterior vaginal wall ( cystocele ) . The primary outcome was a composite of the objective anatomical design ation of stage 0 ( no prolapse ) or 1 ( position of the anterior vaginal wall more than 1 cm above the hymen ) , according to the Pelvic Organ Prolapse Quantification system , and the subjective absence of symptoms of vaginal bulging 12 months after the surgery . RESULTS Of 389 women who were r and omly assigned to a study treatment , 200 underwent prolapse repair with the transvaginal mesh kit and 189 underwent traditional colporrhaphy . At 1 year , the primary outcome was significantly more common in the women treated with transvaginal mesh repair ( 60.8 % ) than in those who underwent colporrhaphy ( 34.5 % ) ( absolute difference , 26.3 percentage points ; 95 % confidence interval , 15.6 to 37.0 ) . The surgery lasted longer and the rates of intraoperative hemorrhage were higher in the mesh-repair group than in the colporrhaphy group ( P<0.001 for both comparisons ) . Rates of bladder perforation were 3.5 % in the mesh-repair group and 0.5 % in the colporrhaphy group ( P=0.07 ) , and the respective rates of new stress urinary incontinence after surgery were 12.3 % and 6.3 % ( P=0.05 ) . Surgical reintervention to correct mesh exposure during follow-up occurred in 3.2 % of 186 patients in the mesh-repair group . CONCLUSIONS As compared with anterior colporrhaphy , use of a st and ardized , trocar-guided mesh kit for cystocele repair result ed in higher short-term rates of successful treatment but also in higher rates of surgical complications and postoperative adverse events . ( Funded by the Karolinska Institutet and Output:	In the anterior compartment , mesh repairs seem to offer clearly superior efficacy and durability of results compared to native tissue repairs , but with an equally clear increase in complication rates . As far as the apical compartment is concerned , sacrocolpopexy is the most efficacious , yet the most invasive procedure .
MS21322	*TASK* the task is to summarize an input biomedical literature in six sentences *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 COPD is a major cause of disability , but little is known about how disability develops in this condition . Methods The authors analysed data from the Function , Living , Outcomes and Work ( FLOW ) Study which enrolled 1202 Kaiser Permanente Northern California members with COPD at baseline and re-evaluated 1051 subjects at 2-year follow-up . The authors tested the specific hypothesis that the development of specific non-respiratory impairments ( abnormal body composition and muscle strength ) and functional limitations ( decreased lower extremity function , poor balance , mobility-related dyspnoea , reduced exercise performance and decreased cognitive function ) will determine the risk of disability in COPD , after controlling for respiratory impairment ( FEV1 and oxygen saturation ) . The Valued Life Activities Scale was used to assess disability in terms of a broad range of daily activities . The primary disability outcome measure was defined as an increase in the proportion of activities that can not be performed of 3.3 % or greater from baseline to 2-year follow-up ( the estimated minimal important difference ) . Multivariable logistic regression was used for analysis . Results Respiratory impairment measures were related to an increased prospect i ve risk of disability ( multivariate OR 1.75 ; 95 % CI 1.26 to 2.44 for 1 litre decrement of FEV1 and OR 1.57 per 5 % decrement in oxygen saturation ; 95 % CI 1.13 to 2.18 ) . Non-respiratory impairment ( body composition and lower extremity muscle strength ) and functional limitations ( lower extremity function , exercise performance , and mobility-related dyspnoea ) were all associated with an increased longitudinal risk of disability after controlling for respiratory impairment ( p<0.05 in all cases ) . Non-respiratory impairment and functional limitations were predictive of prospect i ve disability , above- and -beyond sociodemographic characteristics , smoking status and respiratory impairment ( area under the receiver operating characteristic curve increased from 0.65 to 0.75 ; p<0.001 ) . Conclusions Development of non-respiratory impairment and functional limitations , which reflect the systemic nature of COPD , appear to be critical determinants of disablement . Prevention and treatment of disability require a comprehensive approach to the COPD patient BACKGROUND Use of nutritional supplements in depleted patients with chronic obstructive pulmonary disease ( COPD ) requires optimization between positive effects on outcome and potential acute adverse effects on metabolism and exercise performance . OBJECTIVE The aim of this study was to investigate the acute effects of nutritional supplements on metabolism and exercise capacity in stable COPD patients . DESIGN In part 1 , the effects of 3 different energy loads ( placebo , 1046 kJ , and 2092 kJ ) with a normal distribution of macronutrients were investigated in 14 COPD patients . In part 2 , the effects of a fat-rich compared with a carbohydrate-rich supplement ( both 1046 kJ ) were studied in 11 COPD patients . The study was performed in a r and omized , double-blind , crossover fashion . Metabolic and ventilatory variables were measured postpr and ially and during a submaximal cycle endurance exercise test . RESULTS Overall , no immediate negative effects of the supplements were found in part 1 . A slight but significant postpr and ial increase in respiratory quotient was found after the 1046-kJ and 2092-kJ supplements compared with placebo . There was no significant difference in metabolism or exercise capacity after a fat-rich or carbohydrate-rich supplement . Surprisingly , the change in shortness of breath ( postpr and ial compared with prepr and ial ) was significantly greater after the fat-rich supplement . CONCLUSIONS An energy load up to 2092 kJ had no adverse immediate effect in COPD patients compared with placebo . The subjects who consumed the fat-rich supplement experienced more shortness of breath than did the subjects who consumed the carbohydrate-rich supplement The impact of oral nutritional supplementation during an acute exacerbation of COPD on functional status was assessed through measuring change in lung function , strength testing , and general well-being . Subjects hospitalized for an acute exacerbation of COPD ( n = 33 ) were r and omized to extra nutritional support or the regular hospital care . They consumed an additional 10 kcal/kg/d . Outcome measures were measured at 2 wk as change scores . Forced vital capacity ( % predicted ) improved in the treatment group as compared with the control group ( + 8.7 % versus -3.5 % , p = 0.015 ) , and change in FEV1 was in the same direction but not significantly different ( p = 0.099 ) . There were no changes in h and grip strength or respiratory muscle strength , but there was a trend towards more improvement in the general well-being score ( + 11.96 versus -10.25 , p = 0.066 ) . Almost all subjects were in negative nitrogen balance , indicating muscle wasting . The degree of muscle wasting was strongly correlated with the dose of corticosteroids ( r = 0.73 , p < 0.005 ) . In conclusion , it is difficult to prevent important muscle wasting in patients with COPD treated with corticosteroids , but some small gains were observed with increased dietary intake Background In chronic respiratory failure ( CRF ) , body composition strongly predicts survival . Methods A prospect i ve r and omised controlled trial was undertaken in malnourished patients with CRF to evaluate the effects of 3 months of home rehabilitation on body functioning and composition . 122 patients with CRF on long-term oxygen therapy and /or non-invasive ventilation ( mean ( SD ) age 66 ( 10 ) years , 91 men ) were included from eight respiratory units ; 62 were assigned to home health education ( controls ) and 60 to multimodal nutritional rehabilitation combining health education , oral nutritional supplements , exercise and oral testosterone for 90 days . The primary endpoint was exercise tolerance assessed by the 6-min walking test ( 6MWT ) . Secondary endpoints were body composition , quality of life after 3 months and 15-month survival . Results Mean ( SD ) baseline arterial oxygen tension was 7.7 ( 1.2 ) kPa , forced expiratory volume in 1 s 31 (13)% predicted , body mass index ( BMI ) 21.5 ( 3.9 ) kg/m2 and fat-free mass index ( FFMI ) 15.5 ( 2.4 ) kg/m2 . The intervention had no significant effect on 6MWT . Improvements ( treatment effect ) were seen in BMI ( + 0.56 kg/m2 , 95 % CI 0.18 to 0.95 , p=0.004 ) , FFMI ( + 0.60 kg/m2 , 95 % CI 0.15 to 1.05 , p=0.01 ) , haemoglobin ( + 9.1 g/l , 95 % CI 2.5 to 15.7 , p=0.008 ) , peak workload ( + 7.2 W , 95 % CI 3.7 to 10.6 , p<0.001 ) , quadriceps isometric force ( + 28.3 N , 95 % CI 7.2 to 49.3 , p=0.009 ) , endurance time ( + 5.9 min , 95 % CI 3.1 to 8.8 , p<0.001 ) and , in women , Chronic Respiratory Question naire ( + 16.5 units , 95 % CI 5.3 to 27.7 , p=0.006 ) . In a multivariate Cox analysis , only rehabilitation in a per- protocol analysis predicted survival ( HR 0.27 , 95 % CI 0.07 to 0.95 , p=0.042 ) . Conclusions Multimodal nutritional rehabilitation aim ed at improving body composition increased exercise tolerance , quality of life in women and survival in compliant patients , supporting its incorporation in the treatment of malnourished patients with CRF . Clinical Trial number NCT00230984 Nutritional depletion commonly occurs in patients with COPD , causing muscle wasting and impaired physiologic function . Two hundred seventeen patients with COPD participated in a placebo-controlled , r and omized trial investigating the physiologic effects of nutritional intervention alone ( N ) for 8 wk or combined with the anabolic steroid n and rolone decanoate ( N + A ) . N and rolone decanoate or placebo ( P ) was injected intramuscularly ( women , 25 mg ; men , 50 mg ) in a double-blind fashion on Days 1 , 15 , 29 , and 43 . Nutritional intervention consisted of a daily high caloric supplement ( 420 kcal ; 200 ml ) . Also , all patients participated in an exercise program . In the depleted patients , both treatment regimens induced a similar significant body weight gain ( 2.6 kg ) but different body compositional changes . Particularly in the last 4 wk of treatment , weight gain in the N group was predominantly due to an expansion of fat mass ( p < 0.03 versus P and N + A ) , whereas the relative changes in fat-free mass ( FFM ) and other measures of muscle mass were more favorable in the N + A group ( p < 0.03 versus P ) . Maximal inspiratory mouth pressure improved within both treatment groups in the first 4 wk of treatment , but after 8 wk only N + A was significantly different from P ( p < 0.03 ) . Nutritional supplementation in combination with a short course of anabolic steroids may enhance the gain in FFM and respiratory muscle function in depleted patients with COPD without causing adverse side effects The objective of the study was to further unravel the prognostic significance of body weight changes in patients with COPD . Two survival analyses were performed : ( 1 ) a retrospective study , including 400 patients with COPD none of whom had received nutritional therapy ; ( 2 ) a post hoc analysis of a prospect i ve study , including 203 patients with COPD who had participated in a r and omized placebo-controlled trial . There was no overlap between the patient groups . Baseline characteristics of all patients were collected on admission to a pulmonary rehabilitation center in stable clinical condition . In the prospect i ve r and omized placebo-controlled trial , the physiologic effects of nutritional therapy alone ( n = 71 ) or in combination with anabolic steroid treatment ( n = 67 ) after 8 wk was studied in patients with COPD prestratified into a depleted group and a nondepleted group . Mortality was assessed as overall mortality . The Cox proportional hazards model was used to quantify the relationship between the baseline variables age , sex , spirometry , arterial blood gases , body mass index ( BMI ) , smoking , and subsequent overall mortality . Additionally , the influence of treatment response on mortality was investigated in the prospect i ve study . The retrospective study revealed that low BMI ( p < 0.001 ) , age ( p < 0.0001 ) and low PaO2 ( p < 0.05 ) were significant independent predictors of increased mortality . After stratification of the group into BMI quintiles a threshold value of 25 kg/m2 was identified below which the mortality risk was clearly increased . In the prospect i ve study , weight gain ( > 2 kg/8 wk ) in depleted and nondepleted patients with COPD , as well as increase in maximal inspiratory mouth pressure during the 8-wk treatment , were significant predictors of survival . On Cox regression analysis weight change entered as a time-dependent covariate remained an independent predictor of mortality in addition to all variables that were entered in the retrospective study . The combined results of the two survival analyses provide evidence to support the hypothesis that body weight has an independent effect on survival in COPD . Moreover the negative effect of low body weight can be reversed by appropriate therapy in some of the patients with COPD Study objectives Patients with chronic obstructive pulmonary disease ( COPD ) have low exercise capacity and low content of high energetic phosphates in their skeletal muscles . The aim of the present study was to investigate whether creatine supplementation together with exercise training may increase physical performance compared with exercise training in patients with COPD . Design In a r and omized , double-blind , placebo-controlled study , 23 patients with COPD ( forced expiratory volume in one second [ FEV1 ] < 70 % of predicted ) were r and omized to oral creatine ( n = 13 ) or placebo ( n = 10 ) supplementation during an 8-week rehabilitation programme including exercise training . Physical performance was assessed by Endurance Shuttle Walking Test ( ESWT ) , dyspnea and leg fatigue with Borg CR-10 , quality of life with St George ’s Respiratory Question naire ( SGRQ ) . In addition , lung function test , artery blood gases , grip strength test , muscle strength and fatigue in knee extensors were measured . Results COPD patients receiving creatine supplementation increased their average walking time by 61 % ( ESWT ) ( p < 0.05 ) after the training period compared with 48 % ( p = 0.07 ) in the placebo group . Rated dyspnea directly after the ESWT decreased significantly from 7 to 5 ( p < 0.05 ) in the creatine group . However , the difference between the groups was not statistically significant neither in walking time nor in rated dyspnea . Creatine supplementation did not increase the health related quality of life , lung function , ar Output:	It also led to improved exercise performance and enhancement of exercise rehabilitation programmes . This systematic review and meta- analysis demonstrates that nutritional support in COPD results in significant improvements in a number of clinical ly relevant functional outcomes , complementing a previous review showing improvements in nutritional intake and weight
MS21323	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Environmental stimulus , especially noise and light , is thought to disrupt sleep in patients in the intensive care unit ( ICU ) . This study aim ed to determine the physiological and psychological effects of ICU noise and light , and of earplugs and eye masks , used in these conditions in healthy subjects . Methods Fourteen subjects underwent polysomnography under four conditions : adaptation , baseline , exposure to recorded ICU noise and light ( NL ) , and NL plus use of earplugs and eye masks ( NLEE ) . Urine was analyzed for melatonin and cortisol levels . Subjects rated their perceived sleep quality , anxiety levels and perception of environmental stimuli . Results Subjects had poorer perceived sleep quality , more light sleep , longer rapid eye movement ( REM ) latency , less REM sleep when exposed to simulated ICU noise and light ( P < 0.05 ) . Nocturnal melatonin ( P = 0.007 ) and cortisol secretion levels ( P = 0.004 ) differed significantly by condition but anxiety levels did not ( P = 0.06 ) . Use of earplugs and eye masks result ed in more REM time , shorter REM latency , less arousal ( P < 0.05 ) and elevated melatonin levels ( P = 0.002 ) . Conclusions Earplugs and eye masks promote sleep and hormone balance in healthy subjects exposed to simulated ICU noise and light , making their promotion in ICU patients reasonable BACKGROUND Post-anaesthesia care units ( PACUs ) with 24/7 activity and consequently artificial light and noise may disturb the sleep of patients who require prolonged medical supervision . After one postoperative night , we compared sleep quality in patients with and without noise ( earplug ) and light ( eye mask ) protection . METHODS After ethical board approval , 46 patients without any neurological or respiratory failure undergoing major non-cardiac surgery were prospect ively included . They were r and omized to sleep with or without protective devices during the first postoperative night in the PACU . Sleep quality was simultaneously measured by sleep- quality scales ( Spiegel score and Medical Outcomes Study Sleep ) , nurses ' assessment , and through a wrist actigraph ( Actiwatch ) . Secondary outcomes such as pain control and nocturnal activity were recorded . Comparisons between groups were made by Student 's t-test or non-parametric test for repeated measures as appropriate ( SPSS 10.0 ) . A P-value < 0.05 was considered significant . RESULTS Data from 41 patients were analysed . Protective devices during the first postoperative night prevented a decrease in sleep quality compared with st and ard care , as evaluated by the Spiegel scale : 20 ( 4 ) vs 15 ( 5 ) , P=0.006 . These devices significantly decreased the need for a nap [ 50 % 95 % confidence interval ( CI ) ( 20 - 80 ) vs 95 % 95 % CI ( 85 - 100 ) , P<0.001 ] , but had no effect on sleep length evaluated by Actiwatch . The total consumption of morphine was significantly reduced in the first 24 h [ respectively , 15(12 ) mg and 27(17 ) mg , P=0.02 ] . CONCLUSIONS Earplugs and eye masks applied in the PACU during the first postoperative night significantly preserve sleep quality . Such non-invasive and cheap devices may be generalized in the PACU or in intensive care units Abstract Background : Poor sleep quality ( SQ ) is common among patients after coronary artery bypass graft surgery ( CABG ) . This study attempted to determine the status of SQ following an intervention based on the PRECEDE-PROCEED model in patients with poor SQ after CABG . Methods : This study was a r and omized clinical trial . The study sample , including 100 patients referred to the Cardiac Rehabilitation Clinic of Tehran Heart Center , was assigned either to the intervention ( recipient of exercise and lifestyle training plus design ed intervention based on the PRECEDE-PROCEED model ) or to the control group ( recipient of exercise and lifestyle training ) . Eight training sessions over 8 weeks were conducted for the intervention group . Predisposing , enabling , and reinforcing factors as well as social support and SQ were measured in the intervention group before and one month after the intervention and compared to those in the control group at the same time points . Results : The mean age of the patients in the intervention ( 24 % women ) and control ( 24 % women ) groups was 59.3 ± 7.3 and 59.5 ± 9.3 years , respectively . The results showed that the mean scores of SQ ( p value < 0.001 ) , knowledge ( p value < 0.001 ) , beliefs ( p value < 0.001 ) , sleep self-efficacy ( p value < 0.001 ) , enabling factors ( p value < 0.001 ) , reinforcing factors ( p value < 0.001 ) , and social support ( p value < 0.001 ) were significantly different between the intervention and control groups after the intervention . Conclusion : Adding an intervention based on the PRECEDE-PROCEED model to the cardiac rehabilitation program may further improve the SQ of patients INTRODUCTION : Poor sleep quality is common among patients following cardiopulmonary artery bypass graft surgery . Pain , stress , anxiety and poor sleep quality may be improved by massage therapy . OBJECTIVE : This study evaluated whether massage therapy is an effective technique for improving sleep quality in patients following cardiopulmonary artery bypass graft surgery . METHOD : Participants included cardiopulmonary artery bypass graft surgery patients who were r and omized into a control group and a massage therapy group following discharge from the intensive care unit ( Day 0 ) , during the postoperative period . The control group and the massage therapy group comprised participants who were subjected to three nights without massage and three nights with massage therapy , respectively . The patients were evaluated on the following mornings ( i.e. , Day 1 to Day 3 ) using a visual analogue scale for pain in the chest , back and shoulders , in addition to fatigue and sleep . Participants kept a sleep diary during the study period . RESULTS : Fifty-seven cardiopulmonary artery bypass graft surgery patients were enrolled in the study during the preoperative period , 17 of whom were excluded due to postoperative complications . The remaining 40 participants ( male : 67.5 % , age : 61.9 years ± 8.9 years , body mass index : 27.2 kg/m2 ± 3.7 kg/m2 ) were r and omized into control ( n = 20 ) and massage therapy ( n = 20 ) groups . Pain in the chest , shoulders , and back decreased significantly in both groups from Day 1 to Day 3 . The participants in the massage therapy group had fewer complaints of fatigue on Day 1 ( p = 0.006 ) and Day 2 ( p = 0.028 ) in addition , they reported a more effective sleep during all three days ( p = 0.019 ) when compared with the participants in the control group . CONCLUSION : Massage therapy is an effective technique for improving patient recovery from cardiopulmonary artery bypass graft surgery because it reduces fatigue and improves sleep Introduction Intensive care unit ( ICU ) environmental factors such as noise and light have been cited as important causes of sleep deprivation in critically ill patients . Previous studies indicated that using earplugs and eye masks can improve REM sleep in healthy subjects in simulated ICU environment , and improve sleep quality in ICU patients . This study aim ed to determine the effects of using earplugs and eye masks with relaxing background music on sleep , melatonin and cortisol levels in ICU patients . Methods Fifty patients who underwent a scheduled cardiac surgery and were expected to stay at least 2 nights in Cardiac Surgical ICU ( CSICU ) were included . They were r and omized to sleep with or without earplugs and eye masks combined with 30-minute relaxing music during the postoperative nights in CSICU . Urine was analyzed for nocturnal melatonin and cortisol levels . Subjective sleep quality was evaluated using the Chinese version of Richards-Campbell Sleep Question naire ( a visual analog scale , ranging 0–100 ) . Results Data from 45 patients ( 20 in intervention group , 25 in control group ) were analyzed . Significant differences were found between groups in depth of sleep , falling asleep , awakenings , falling asleep again after awakening and overall sleep quality ( P < 0.05 ) . Perceived sleep quality was better in the intervention group . No group differences were found in urinary melatonin levels and cortisol levels for the night before surgery , and the first and second nights post-surgery ( P > 0.05 ) . The urinary melatonin levels of the first and second postoperative nights were significantly lower than those of the night before surgery ( P = 0.01 ) . The opposite pattern was seen with urinary cortisol levels ( P = 0.00 ) . Conclusion This combination of non-pharmacological interventions is useful for promoting sleep in ICU adult patients ; however , any influence on nocturnal melatonin levels and cortisol level may have been masked by several factors such as the timing of surgery , medication use and individual differences . Larger scale studies would be needed to examine the potential influences of these factors on biological markers and intervention efficacy on sleep . Trial registration Chinese Clinical Trial Registry : ChiCTR-IOR-14005511 . Registered 21 November 2014 Background : Coronary artery bypass grafting ( CABG ) in high-risk patients is associated with significant perioperative complications and anxiety . Prevention of these postoperative complications and anxiety is important in the improvement of clinical outcomes following CABG . Objective : The objective of the study was to evaluate the effect of nurse-initiated preoperative education and counseling on postoperative complications and anxiety symptoms following CABG . Methods : In this prospect i ve and r and omized trial , 40 patients were divided into the study and control groups . All patients received st and ard preoperative and postoperative care , but the study group patients also completed a structured education and counseling course supervised by design ated nurses 3 days before the surgery . Anxiety symptoms were assessed by Zung ’s self-rating anxiety scale ( SAS ) on the day of admission and at 3 days after the surgery . Results : There was no statistically significant difference in the baseline characteristics or operational data between the 2 groups ( P > .05 ) . Following the surgery , the rate of complications such as lower extremity edema , urinary retention , constipation , respiratory infection , and deep venous thrombosis in the study group was lower than in the control group ( P < .05 ) . The mean postoperative SAS scores in the study group was lower than in the control group ( 40.1 [ SD , 6.5 ] vs 48.9 [ SD , 7.3 ] ; P = .01 ) , and the proportion of patients with a SAS score greater than 40 in the study group was also lower than in the control group ( 15 % vs 45 % , P = .041 ) . Conclusions : Nurse-initiated preoperational education and counseling were associated with a reduced rate of perioperative complications and a reduced level of anxiety following CABG AIMS AND OBJECTIVES To evaluate the effectiveness of an individualised programme to promote self-care in sleep-activity in patients with coronary artery disease . BACKGROUND Recent scientific findings have shown that low physical exercise and stress interfere with coronary artery disease patients ' sleep quality and sleep efficiency independent of gender , age and co-morbidity . DESIGN A r and omised pretest-post-test control design . METHODS Forty-seven patients who had undergone a coronary revascularisation procedure and /or pharmacological treatment three to seven weeks earlier at a general hospital were r and omised to either an intervention group or a control group . Data collection was carried out by question naires , a study -specific sleep diary and actigraphy registration for 10 consecutive 24-hour periods , with a follow-up after three to four months . The intervention group underwent a nurse-led individualised education programme to promote self-care of sleep-activity . Sleep habits and sleep-related lifestyle together formed the basis for setting up individual goals together with the nurse . Individual advice on physical training , relaxation exercise and a CD-based relaxation programme was provided by a physiotherapist . Both groups received a brochure about sleep and stress . RESULTS At a three- to four-month follow-up , the main improvements were seen in the intervention group regarding sleep quality , sleep duration and sleep efficiency in the sleep diary and sleep efficiency in actigraphy . Statistical improvements in health-related quality of life were revealed . This was not so obvious in the control group . CONCLUSIONS An individualised intervention programme to promote self-care of sleep-activity including relaxation in patients with coronary artery disease led by a nurse may improve sleep quality . However , a longitudinal study to promote self-care in sleep-activity should be performed using a larger sample and multiple sites with continuous follow-ups to determine whether any positive effects remain stable over time . RELEVANCE TO CLINICAL PRACTICE Implementation of a multiprofessional individualised programme to promote self-care of sleep-activity including relaxation based on patients ' needs , supported by a healthcare team and led by nurses , is important in clinical practice Disturbed sleep and sleep deprivation is common in patients in critical care setting s. Noise and inappropriate use of light/dark cycles are two of the causes of sleep interruptions . The purpose of the study was to evaluate eye masks and earplugs to help control patients ' exposure to noise and light within the critical care environment . An intervention study using a two group post-test quasi-experimental design of high dependency patients within a cardiothoracic critical care unit was undertaken by a group of critical care n Output:	Significant improvement was found in the scores assessing sleep quality among studies testing interventions such as earplugs , sleeping masks , muscle relaxation , posture and relaxation training , white noise , and educational strategies . Conclusion : significant improvement was found among the scores assessing sleep in the studies testing interventions such as earplugs , sleeping masks , muscle relaxation , posture and relaxation training , white noise and music , and educational strategies
MS21324	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Our goal was to investigate whether ambulatory smoking cessation among patients in a cardiologic department would ( 1 ) reduce the number of smokers by at least 25 % after 12 months compared to a control group and ( 2 ) influence whether the individual patient was readmitted to hospital . We used a r and omised , controlled , prospect i ve intervention project design . MATERIAL S AND METHODS Everyone hospitalised during the project period was screened . Those who fulfilled the criteria for inclusion were r and omised for inclusion in either the intervention group or the control group . Both groups were given the department 's smoking cessation information . In addition , the intervention group attended five ambulatory smoking cessation intervention sessions . Each patient 's smoking status was registered after 12 months . chi2-test and logistic regression analysis were used to test differences , associations and control of confounders . RESULTS In all , 3,982 patients were screened , 29.5 % of whom were smokers . The study included 105 patients : 54 in the intervention group and 51 in the control group . After 12 months , 52 % of those in the intervention group compared to 39 % in the control group had become non-smokers , which was non-significant ( p = 0,14 ) . Ischemic heart disease ( IHS ) was significantly associated with smoking cessation . After adjustment for this confounder , the result was enhanced ( p = 0,06 ) . Readmission to hospital was not affected by smoking cessation ( p = 0,73 ) . DISCUSSION Ambulatory smoking cessation intervention had no significant effect on smoking cessation on an unselected group of patients in a cardiologic hospital department . The project does indicate that ambulatory smoking cessation interventions could have an effect on patients with IHS BACKGROUND This study examined the 1-year effects of a minimal-contact smoking cessation intervention for cardiac in patients . METHODS The multicenter study included cardiac in patients who had smoked prior to hospitalization . A pretest-posttest quasi-experimental design was used . Patients ' experimental condition depended on the hospital they were assigned to . The design was partially r and omized : 4 of the 11 hospitals selected the experimental condition themselves ( 2 experimental , 2 control ) , while the remaining 7 hospitals were r and omly assigned . The experimental group consisted of patients of 5 hospitals ( N = 388 ) . Patients of 6 other hospitals served as the control group ( N = 401 ) . The intervention included stop-smoking advice by the cardiologist , brief counseling by the nurse , the provision of self-help material s , and aftercare by the cardiologist . RESULTS Logistic regression analyses controlling for baseline differences and covariates did not show significant intervention effects on point prevalence and continuous abstinence . The study also showed that the outcomes were not significantly related to the way hospitals were assigned to the experimental condition . CONCLUSIONS While short-term effects were found , the minimal-contact intervention did not result in significant effects after 12 months , at least if patients lost to follow-up were treated as posttest smokers . Efforts should be made to improve the intervention , especially the aftercare BACKGROUND Although smoking cessation is essential for prevention of secondary cardiovascular disease ( CVD ) , many smokers do not stop smoking after hospitalization . Mild depressive symptoms are common during hospitalization for CVD . We hypothesized that depressive symptoms measured during hospitalization for acute CVD would predict return to smoking after discharge from the hospital . METHODS This was a planned secondary analysis of data from a placebo-controlled , double-blind , r and omized trial of bupropion hydrochloride therapy in 245 smokers hospitalized for acute CVD . All subjects received smoking counseling in the hospital and for 12 weeks after discharge . Depressive symptoms were measured during hospitalization with the Beck Depression Inventory ( BDI ) , and smoking cessation was biochemically vali date d at 2-week , 12-week , and 1-year follow-up . The effect of depressive symptoms on smoking cessation was assessed using multiple logistic regression and survival analyses . RESULTS Twenty-two percent of smokers had moderate to severe depressive symptoms ( BDI > or= 16 ) during hospitalization . These smokers were more likely to resume smoking by 4 weeks after discharge ( P= .007 ; incidence rate ratio , 2.40 ; 95 % confidence interval , 1.48 - 3.78 ) than were smokers with lower BDI scores . Smokers with low BDI scores were more likely to remain abstinent than were those with high BDI scores at 3-month follow-up ( 37 % vs 15 % ; adjusted odds ratio , 3.02 ; 95 % confidence interval , 1.28 - 7.09 ) and 1-year follow-up ( 27 % vs 10 % ; adjusted odds ratio , 3.77 ; 95 % confidence interval , 1.31 - 10.82 ) . We estimate that 27 % of the effect of the BDI score on smoking cessation was mediated by nicotine withdrawal symptoms . CONCLUSIONS Moderate to severe depressive symptoms during hospitalization for acute CVD are independently associated with rapid relapse to smoking after discharge and lower rates of smoking cessation at long-term follow-up . The relationship was mediated in part by the stronger nicotine withdrawal symptoms experienced by smokers with higher depressive symptoms Background : Guidelines recommend that smoking cessation interventions are offered in all clinical setting s to all smokers willing to make a quit attempt . Since the effectiveness of routine provision of behavioural counselling and nicotine replacement therapy ( NRT ) to smokers admitted to hospital has not been established , a r and omised controlled trial of these interventions given together compared with counselling alone or minimal intervention was performed in hospital in patients . Methods : Medical and surgical in patients who were current smokers at the time of admission were r and omised to receive either usual care ( no additional advice at admission ) , counselling alone ( 20 minute intervention with written material s ) , or NRT plus counselling ( counselling intervention with a 6 week course of NRT ) . Continuous and point prevalence abstinence from smoking ( vali date d by exhaled carbon monoxide < 10 ppm ) was measured at discharge from hospital and at 3 and 12 months , and self-reported reduction in cigarette consumption in smokers was assessed at 3 and 12 months . Results : 274 inpatient smokers were enrolled . Abstinence was higher in the NRT plus counselling group ( n=91 ) than in the counselling alone ( n=91 ) or usual care ( n=92 ) groups . The difference between the groups was significant for vali date d point prevalence abstinence at discharge ( 55 % , 43 % , 37 % respectively , p=0.045 ) and at 12 months ( 17 % , 6 % , 8 % , p=0.03 ) . The respective differences in continuous vali date d abstinence at 12 months were 11 % , 4 % , 8 % ( p=0.25 ) . There was no significant difference between counselling alone and usual care , or in reduction in cigarette consumption between the treatment groups . Conclusions : NRT given with brief counselling to hospital in patients is an effective routine smoking cessation intervention Recent findings suggest that smokers who are hospitalized experience significant craving for cigarettes . Thus , nicotine replacement therapy ( NRT ) may be a particularly important tool for use during hospitalization . The goal of this study is to evaluate the utilization of the transdermal nicotine patch and /or nicotine gum by hospitalized smokers . The data represented in this article are from 580 smokers who participated in a study of a motivational intervention for smoking cessation that was delivered during hospitalization . The primary outcome for this analysis was use of NRT during hospitalization . The results revealed that , among the entire sample , only 7.1 % of the overall sample used NRT during hospitalization ; 6 % of the hospitalized smokers used the transdermal nicotine patch , and 1.1 % used nicotine gum . Use of NRT was significantly greater among patients who reported that they were doing anything to help themselves quit smoking at the time of admission ( OR=4.1 ) , those who were seriously planning to quit smoking within the next 30 days ( OR=2.36 ) , those who were nicotine dependent ( OR=2.81 ) , and those for whom a physician had ever offered to prescribe NRT (OR=1.9).The finding that there is a very low rate of NRT use during hospitalization provides important information to hospital-based care providers and smoking cessation intervention planners . Barriers to NRT use among hospitalized patients should be identified , and strategies design ed to maximize use when appropriate . TheAHCPR Guideline on Smoking Cessation recommends routine use of NRT in health care setting s. Further research is needed to determine why NRT use was so low . In addition , these data suggest that efforts to increase NRT use during hospitalization are needed Cigarette smoking is a major risk factor for head and neck cancer , and individuals who continue to smoke past diagnosis and treatment are at elevated risk for further disease . In a r and omized controlled trial , a state of the art provider-delivered smoking cessation intervention was compared to a usual care advice control condition . The intervention consisted of surgeon- or dentist-delivered advice to stop smoking , a contracted quit date , tailored written material s , and booster advice sessions . Subjects were 186 patients with newly diagnosed first primary squamous cell carcinomas of the upper aerodigestive tract who had smoked cigarettes within the past year . At r and omization , 88.2 % of subjects were current smokers . At 12-month follow-up , 70.2 % of subjects completing the trial ( n = 114 ) were continuous abstainers ; among baseline smokers alone the continuous abstinence ( CA ) rate was 64.6 % . The cotinine validation rate at 12 months was 89.6 % . Modeling techniques were utilized in order to derive expected CA rates , which included noncompleter subjects ( n = 72 ) . The CA rate expected at 1 year for the entire patient population was 64.2 % , and for smokers alone the expected CA rate was 59.4 % . Logistic regression analysis carried out on baseline smokers identified predictors of 12-month CA status . These included medical treatment , stage of change , age , nicotine dependence , and race . The intervention effect was not significant , although the sign of the effect was positive . Based on these findings , we recommend systematic brief advice to stop smoking for head and neck cancer patients , with a stepped care approach for patients less able to quit A controlled evaluation of a minimal-contact smoking cessation intervention was conducted with 213 in patients and out patients at a Veterans Administration Medical Center ( VAMC ) . The intervention had three components : Brief consultation from a health practitioner ; administration of a self-help smoking cessation manual ; and provision of an incentive to adhere to recommendations in the manual . Enrollment procedures differed from those of many other smoking-intervention trials in that , instead of enrolling only smokers who were motivated to quit , all patients who smoked and who would normally be considered eligible for a smoking-cessation intervention were included . The evaluation examined acceptability of the program to patients who smoked , overall effectiveness of the intervention , and efficacy of the intervention for specific patient demographic , social status , and health status groups . The program had a high degree of acceptance by patients who smoked , with over 60 % agreeing to participate and take home the self-help smoking-cessation manual . The program was effective in getting patients to reduce their daily smoking , and marginally effective in influencing smoking cessation , with some patient groups exhibiting higher cessation rates than others . Special problems to be considered when attempting to influence groups of smokers at high levels of psychological stress and with low levels of education and income -- factors normally associated with high rates of smoking and failure in traditional smoking-cessation programs -- are discussed in light of the results obtained BACKGROUND Cessation rates in smokers attending special clinics or their General Practitioners can be increased by transdermal nicotine ( TNS ) . This study assesses the efficacy of TNS as an adjunct to advice and support in helping patients attending hospital with smoking-related diseases to stop smoking . METHODS In a double-blind , placebo-controlled , r and omized manner , 234 in patients and out patients with smoking-related respiratory or cardiovascular disease , aged 18 - 75 years , who were willing to try to stop smoking , were advised by their hospital doctor to stop smoking . This was reinforced by repeated advice and encouragement from the Smoking Cessation Counsellor initially and at 2 , 4 , 8 and 12 weeks , supplemented by a 24 h patch in adjusted doses over that period . Those not smoking at 12 weeks were followed up at 26 and 52 weeks . Self-reported complete abstinence from 12 to 52 weeks was vali date d by expired air carbon monoxide measurement at 12 , 26 and 52 weeks . RESULTS Twenty-four ( 21 % ) of 115 TNS patients were verified as non-smokers at 12 , 26 and 52 weeks and cl aim ed continued abstinence , compared with 17 ( 14 % ) of 119 in the placebo ( P ) group ( P = 0 center dot 15 ) -5 % confidence limits for odds ratio of abstinence on TNS compared to P : 0 center dot 83 , 3 center dot 37 . Cessation was related to increasing age ( P = 0 center dot 02 ) and lower Output:	High intensity behavioural interventions that begin during a hospital stay and include at least one month of supportive contact after discharge promote smoking cessation among hospitalised patients . These interventions are effective regardless of the patient 's admitting diagnosis . lnterventions of lower intensity or shorter duration have not been shown to be effective in this setting . There is insufficient direct evidence to conclude that adding NRT or bupropion to intensive counselling increases cessation rates over what is achieved by counselling alone , but the evidence of benefit for NRT has strengthened in this up date and the point estimates are compatible with research in other setting s showing that NRT and bupropion are effective
MS21325	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Previous studies showed that decreased cerebral saturation during cardiac surgery is related to adverse postoperative outcome . Therefore , we investigated the influence of intraoperative events on cerebral tissue saturation in patients undergoing cardiac surgery with cardiopulmonary bypass ( CPB ) . A total of 52 adult patients who underwent cardiac surgery using pulsatile CPB were included in this prospect i ve explorative study . Cerebral tissue oxygen saturation ( SctO2 ) was measured in both the left and right cerebral hemisphere . Intraoperative events , involving interventions performed by anesthesiologist , surgeon , and clinical perfusionist , were documented . Simultaneously , in-line hemodynamic parameters ( partial oxygen pressure , partial carbon dioxide pressure , hematocrit , arterial blood pressure , and CPB flow rates ) were recorded . Cerebral tissue saturation was affected by anesthetic induction ( p < .001 ) , placement of the sternal retractor ( p < .001 ) , and initiation ( p < .001 ) as well as termination of CPB ( p < .001 ) . Placement ( p < .001 ) and removal of the aortic cross-clamp ( p = .026 for left hemisphere , p = .048 for right hemisphere ) led to changes in cerebral tissue saturation . In addition , when placing the aortic crossclamp , hematocrit ( p < .001 ) as well as arterial ( p = .007 ) and venous ( p < .001 ) partial oxygen pressures changed . Cerebral tissue oximetry effectively identifies changes related to surgical events or vulnerable periods during cardiac surgery . Future studies are needed to identify methods of mitigating periods of reduced cerebral saturation Background Blood transfusions are common in cardiac surgery , but have been associated with increased morbidity and long-term mortality . Efforts to reduce blood product use during cardiac surgery include fluid restriction to minimize hemodilution , and protocol s to guide transfusion decisions . INVOS is a modality that monitors brain tissue oxygen saturation , and could be useful in guiding decisions to transfuse . However , the role of INVOS ( brain tissue oxygen saturation ) as part of an algorithm to direct blood transfusions during cardiac surgery has not been evaluated . This study was conducted to investigate the value of INVOS as part of a protocol for blood transfusions during cardiac surgery . Methods Prospect i ve , r and omized , blinded clinical trial , on 150 ( 75 per group ) elective cardiac surgery patients . The study was approved by the Institution Ethics committee and all patients gave written informed consent . Data were initially analyzed based on “ intention to treat ” , but subsequently were also analyzed “ per protocol ” . Results When protocol was strictly followed ( “ per protocol analysis ” ) , compared to the control group , significantly fewer patients monitored with INVOS received any blood transfusions ( 46 of 70 patients in INVOS group vs. 55 of 67 patients in the control group , p = 0.029 ) . Similarly , patients monitored with INVOS received significantly fewer units of red blood cell transfusions intraoperatively ( 0.20 ± 0.50 vs. 0.52 ± 0.88 , p = 0.008 ) and overall during hospital stay ( 1.31 ± 1.20 vs. 1.82 ± 1.46 , p = 0.024 ) . When data from all patients ( including patient with protocol violation ) were analyzed together ( “ intention to treat analysis ” ) , the observed reduction of blood transfusions in the INVOS group was still significant ( 51 of 75 patients transfused in the INVOS group vs. 63 of 75 patients transfused in the control group , p = 0.021 ) , but the overall number of units transfused per patient did not differ significantly between the groups ( 1.55 ± 1.97 vs. 1.84 ± 1.41 , p = 0.288 ) . Conclusions Our data suggest that INVOS could be a useful tool as part of an algorithm to guide decisions for blood transfusion in cardiac surgery . Additional data from rigorous , well design ed studies are needed to further evaluate the role of INVOS in guiding blood transfusions in cardiac surgery , and circumvent the limitations of this study .Trial registration Clinical Trials.gov : Background We assessed whether a near-infrared spectroscopy (NIRS)-based algorithm for the personalized optimization of cerebral oxygenation during cardiopulmonary bypass combined with a restrictive red cell transfusion threshold would reduce perioperative injury to the brain , heart , and kidneys . Methods In a r and omized controlled trial , participants in three UK centres were r and omized with concealed allocation to a NIRS ( INVOS 5100 ; Medtronic Inc. , Minneapolis , MN , USA)-based ' patient-specific ' algorithm that included a restrictive red cell transfusion threshold ( haematocrit 18 % ) or to a ' generic ' non-NIRS-based algorithm ( st and ard care ) . The NIRS algorithm aim ed to maintain cerebral oxygenation at an absolute value of > 50 % or at > 70 % of baseline values . The primary outcome for the trial was cognitive function measured up to 3 months postsurgery . Results The analysis population comprised eligible r and omized patients who underwent valve or combined valve surgery and coronary artery bypass grafts using cardiopulmonary bypass between December 2009 and January 2014 ( n = 98 patient-specific algorithm ; n = 106 generic algorithm ) . There was no difference between the groups for the three core cognitive domains ( attention , verbal memory , and motor coordination ) or for the non-core domains psychomotor speed and visuo-spatial skills . The NIRS group had higher scores for verbal fluency ; mean difference 3.73 ( 95 % confidence interval 1.50 , 5.96 ) . Red cell transfusions , biomarkers of brain , kidney , and myocardial injury , adverse events , and health-care costs were similar between the groups . Conclusions These results do not support the use of NIRS-based algorithms for the personalized optimization of cerebral oxygenation in adult cardiac surgery . Clinical trial registration http://www.controlled-trials.com , IS RCT N 23557269 OBJECTIVES The aim of this study is the assessment of the regional cerebral oximetry - NIRS ( near infrared spectroscopy ) as an intraoperative monitoring system to protect the patient against the incidents of brain desaturations . We hypothesize that patients monitored with NIRS present a smaller range of postoperative cognitive dysfunctions ( POCD ) in comparison with those without NIRS monitoring during lumbar spine surgery in a prone position . SETTING S This study was performed at the Clinical Department of Neurosurgery and Oncology of the Central Nervous System , Medical University of Lodz , Pol and . PARTICIPANTS The study completed 43 adult patients qualified for the surgical treatment of lumbar spondylosis . Before the procedures they were r and omized into two subgroups : one monitored intraoperatively by means of NIRS cerebral oximetry ( INVOS 5100 ) , which numbered 13 patients – 30.2 % ( 13 NIRS devices were made available to the authors ) and the other without NIRS intraoperative monitoring , totaling 30 people – 69.8 % . The patients who presented a history of psychiatric , neurological and cardiovascular disorders which impair cognitive processes were disqualified from the study . PRIMARY AND SECONDARY OUTCOME MEASURES A comprehensive battery of neuropsychological tests was preoperatively performed on all patients . The subjects were then divided into two groups : with and without NIRS monitoring . Both groups were statistically homogeneous . Computerized anesthesia records were used to obtain intraoperative data : mean arterial pressure , heart rate , pulsoximetry and cerebral regional oxygenation . The depth of anesthesia monitor was not used . Besides , all the patients passed the same battery of neurocognitive tests 7 days and 1 month postoperatively . The Mann-Whitney test was performed to compare POCD and therefore assess the usefulness of NIRS as a monitoring mechanism during anesthesia in the prone position . RESULTS There was a significant ( p < 0.05 ) difference in the presence of cognitive deficiencies between the subgroup monitored with NIRS and the subgroup without NIRS . It included : Digit Span Test overall score and forward repetition score 7 days after operation , N- back Test results after 30 days in version 0 " back " - time , N-back Test version 1 " back " results in the number of correct answers and the number of errors . CONCLUSIONS NIRS cerebral oximetry may be useful in reducing postoperative cognitive complications in patients operated on in the prone positioning . TRIAL REGISTRATION RNN/556/08/KB – approval of the ethics committee at Medical University of Lodz , Pol and The use of cerebral oximetry to guide intraoperative management has been shown to improve patient outcomes in cardiac surgery . This pilot trial assessed the feasibility of performing a similar study of outcome in patients over the age of 70 years undergoing non-cardiac surgery . Patients over the age of 70 years undergoing total knee or hip arthroplasty or bowel resection surgery were r and omly assigned to have cerebral oximetry values monitored ( intervention group ) or not monitored ( control ) while under general anaesthesia . Indicators of proof of concept were : rate of complications , rate of cerebral desaturation , relationship between cerebral desaturation and complications , and anaesthetist response to cerebral desaturation . Forty patients were recruited and r and omised to a control group ( n=20 ) or an intervention group ( n=20 ) . The proportion of the study population who had a complication was 40 % ( 95 % confidence interval [ CI ] 26 % to 55 % ) . Cerebral desaturation ( < 75 % of baseline ) occurred in only two patients ( 5.0 % ( CI 1.4 % to 16 % ) ) , one in each group , and neither of those patients recorded a complication . Changes to anaesthetic management on the basis of cerebral oximetry values occurred in only two patients in the intervention group ( 10 % ( CI 2.8 % to 30 % ) ) . Maintenance of cerebral oximetry values appeared to be closer to baseline in the intervention group than in the control group but this difference was not significant ( P=0.15 ) . Our results indicated that complications occurred frequently in the study population but did not appear to be associated with cerebral desaturation events . These findings do not support a larger intervention study using the current study population OBJECTIVE The aim of this study was to compare the effect of sevoflurane and propofol on cerebral oxygenation , using regional cerebral oxygen saturation ( SrO2 ) measured by near-infrared spectroscopy ( NIRS ) . STUDY DESIGN Prospect i ve , r and omized , controlled study . PATIENTS AND METHODS Fifty-four patients aged between 18 and 65 years who underwent elective minor surgery ( tumorectomy for breast cancer or inguinal hernia repair ) were r and omly assigned to receive sevoflurane or propofol anaesthesia . Exclusion criteria included pre-existing cerebrovascular diseases , anaemia , ASA > III , blood loss ≥200 mL , arterial hypotension , baseline pulse oximetry < 97 % , sign of sensor low quality of SrO2 or bispectral index , and patients with a forehead area < 6.5 cm . SrO2 , bispectral index , haemodynamic data and anaesthetic doses were recorded during surgery . RESULTS A total of 48 patients were included in the final analysis ( 24 in each group ) . There were no significant differences in mean , minimum and maximum SrO2 between sevoflurane and propofol groups . The relative maximum decrease was higher in propofol anaesthesia than sevoflurane anaesthesia ( 9.6±10.7 versus 4.2±7.2 % ; P=0.048 ) . Cerebral desaturation ( 20 % reduction from SrO2 baseline during 15 seconds ) occurred in 4 patients in propofol group exclusively ( P=0.109 ) . SrO2 adjusted for baseline was higher in the sevoflurane group than in the propofol group ( 67.3±1.8 % versus 64.2±1.7 % ; P=0.018 ) . There were no significant differences in haemodynamic parameters between the two groups . CONCLUSIONS Cerebral cortical oxygenation measured by NIRS may be better preserved with sevoflurane than with propofol . These findings suggest that sevoflurane anaesthesia could be a good option in patients with compromised cerebral oxygenation , given the absence of intracranial hypertension . Further studies with larger sample sizes are required to support our results Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Background The study determined the one year incidence of post operative cognitive decline ( POCD ) and evaluated the effectiveness of an intra-operative anaesthetic intervention in reducing post-operative cognitive impairment in older adults ( over 60 years of age ) undergoing elective orthopaedic or ab Output:	Conclusions Intraoperative cerebral oximetry appears to be associated with a reduction in POCD , although this result should be interpreted with caution given the significant heterogeneity in the studies examined .
MS21326	*TASK* the task is to summarize an input biomedical literature in six sentences *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 energy density ( ED ; kcal/g ) of an entrée influences children 's energy intake ( EI ) , but the effect of simultaneously changing both ED and portion size of an entrée on preschool children 's EI is unknown . In this within-subject crossover study , 3- to 5-year-old children ( 30 boys , 31 girls ) in a daycare facility were served a test lunch once/week for 4 weeks . The amount and type of vegetables and cheeses incorporated into the sauce of a pasta entrée were manipulated to create two versions that varied in ED by 25 % ( 1.6 or 1.2 kcal/g ) . Across the weeks , each version of the entrée was served to the children in each of two portion sizes ( 400 or 300 g ) . Lunch , consumed ad libitum , also included carrots , applesauce , and milk . Decreasing ED of the entrée by 25 % significantly ( P<0.0001 ) reduced children 's EI of the entrée by 25 % ( 63.1+/-8.3 kcal ) and EI at lunch by 17 % ( 60.7+/-8.9 kcal ) . Increasing the proportion of vegetables in the pasta entrée increased children 's vegetable intake at lunch by half of a serving of vegetables ( P<0.01 ) . Decreasing portion size of the entrée by 25 % did not significantly affect children 's total food intake or EI at lunch . Therefore , reducing the ED of a lunch entrée result ed in a reduction in children 's EI from the entrée and from the meal in both portion size conditions . Decreasing ED by incorporating more vegetables into recipes is an effective way of reducing children 's EI while increasing their vegetable intake Summary Background Increases in portion size are thought by many to promote obesity in children . However , this relationship remains unclear . Here , we explore the extent to which a child 's BMI is predicted both by parental beliefs about their child 's ideal and maximum portion size and /or by the child 's own beliefs . Methods Parent – child ( 5–11 years ) dyads ( N = 217 ) were recruited from a r and omized controlled trial ( n = 69 ) and an interactive science centre ( n = 148 ) . For a range of main meals , parents estimated their child 's ‘ ideal ’ and ‘ maximum tolerated ’ portions . Children completed the same tasks . Results An association was found between parents ' beliefs about their child 's ideal ( β = .34 , p < .001 ) and maximum tolerated ( β = .30 , p < .001 ) portions , and their child 's BMI . By contrast , children 's self‐reported ideal ( β = .02 , p = .718 ) and maximum tolerated ( β = −.09 , p = .214 ) portions did not predict their BMI . With increasing child BMI , parents ' estimations aligned more closely with their child 's own selected portions . Conclusions Our findings suggest that when a parent selects a smaller portion for their child than their child self‐selects , then the child is less likely to be obese . Therefore , public health measures to prevent obesity might include instructions to parents on appropriate portions for young children BACKGROUND Informed and engaged parents and healthful home environments are essential for the health of youth . Although research has shown health benefits associated with family meals , to date , no r and omized controlled trial ( RCT ) has been developed to examine the impact of a family meals intervention on behavioral and health outcomes . METHODS / DESIGN The Healthy Home Offerings via the Mealtime Environment ( HOME ) Plus study is a two-arm ( intervention versus attention-only control ) RCT being conducted in Minneapolis/St . Paul . Built on previous pilot research , HOME Plus aims to increase the frequency and healthfulness of family meals and snacks and reduce children 's sedentary behavior , particularly screen time , to promote healthier eating and activity behaviors and prevent obesity . HOME Plus is delivered to families in community setting s. The program includes 10 monthly sessions focused on nutrition and activity education , meal planning and preparation skill development . In addition , five motivational goal - setting phone calls are conducted with parents . The primary outcome measure is age- and gender-adjusted child BMI -z score at post-intervention by treatment group . Secondary household-level outcomes include family meal frequency , home availability of healthful foods ( fruits/vegetables ) and unhealthful foods ( high-fat/sugary snacks ) and beverages ( sugar-sweetened beverages ) , and the quality of foods served at meals and snacks . Secondary child outcomes include dietary intake of corresponding foods and beverages and screen time . CONCLUSIONS The HOME Plus RCT actively engages whole families of 8 - 12 year old children to promote healthier eating and activity behaviors and prevent obesity through promotion of family meals and snacks and limited media use BACKGROUND Previous portion size research in children has focused on the impact of large entrée portions on children 's intake , but less attention has been given to how intake at a meal is affected across a broader range of entrée portions . OBJECTIVE The objective was to assess the effect of serving a range of entrée portions on children 's ad libitum intake and energy density consumed at the meal . DESIGN A within-subject design was used to examine the effect of varying entrée portions ( ie , 100 , 160 , 220 , 280 , 340 , and 400 g ) on children 's ad libitum energy intake of macaroni and cheese and fixed portions of unsweetened applesauce , green beans , and whole-wheat roll served with the entree . Seventeen children ( 10 girls ) , aged 3 to 6 y , were served a series of 6 lunches , which varied only in entrée portion size , once per week . Weight , height , and weighed food intake were measured . RESULTS Increasing portion size increased children 's entrée intake ( P < 0.01 ) and decreased intake of other foods served with the entrée , including fruit and vegetables ( P < 0.0001 ) . As a result , children consumed a more-energy-dense ( kcal/g ) lunch as portion size increased ( P < 0.0001 ) . Further examination showed that BMI percentile moderated the positive association between portion size and entrée intake ( P < 0.01 ) ; overweight children showed greater increases in entree intake with increasing entrée portion . CONCLUSION Serving smaller age-appropriate entrée portions may be one strategy to improve children 's nutritional profile by decreasing intake of energy-dense foods and by promoting intake of fruit and vegetables served with the entree BACKGROUND Research has demonstrated a significant positive association between frequent family meals and children 's dietary intake ; however , the promotion of healthful family meals has not been rigorously tested for key food environment and nutrition-related behavioral outcomes in a r and omized trial . OBJECTIVE To describe family home food environment and nutrition-related parent and child personal and behavioral outcomes of the Healthy Home Offerings via the Mealtime Environment Plus program , the first rigorously tested family meals intervention targeting childhood obesity prevention . DESIGN R and omized controlled trial . Baseline , postintervention ( 12 months , 93 % retention ) , and follow-up ( 21 months , 89 % retention ) data ( surveys and dietary recalls ) were collected . PARTICIPANTS / SETTING Children aged 8 to 12 years ( N=160 ) and their parents were r and omized to intervention ( n=81 ) or control ( n=79 ) groups . INTERVENTION The intervention included five parent goal - setting calls and 10 monthly sessions delivered to families in community setting s that focused on experiential nutrition activities and education , meal planning , cooking skill development , and reducing screen time . MAIN OUTCOME MEASURES Family home food environment outcomes and nutrition-related child and parent personal and behavioral outcomes . STATISTICAL ANALYSES PERFORMED Analyses used generalized linear mixed models . Primary comparisons were contrasts between intervention and control groups at postintervention and follow-up , with adjustments for child age and parent education . RESULTS Compared with control parents , intervention parents showed greater improvement over time in scores of self-efficacy for identifying appropriate portion sizes , with significant differences in adjusted means at both post-intervention ( P=0.002 ) and follow-up ( P=0.01 ) . Intervention children were less likely to consume at least one sugar-sweetened beverage daily at post-intervention than control children ( P=0.04 ) . CONCLUSIONS The Healthy Home Offerings via the Mealtime Environment Plus program involved the entire family and targeted personal , behavioral , and environment factors important for healthful changes in the home food environment and children 's dietary intake . The intervention improved two nutrition-related behaviors and this may inform the design of future family meal interventions Output:	Thematic synthesis of 14 qualitative studies found that parents serve the portion sizes they learn to be appropriate for their child to be fed . Portioning is influenced by parents ' desires for a healthy child with a balanced diet .
MS21327	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Intermittent preventive treatment in pregnancy has not been evaluated outside of Africa . Low birthweight ( LBW , < 2,500 g ) is common in Papua New Guinea ( PNG ) and contributing factors include malaria and reproductive tract infections . Methods From November 2009 to February 2013 , we conducted a parallel group , r and omised controlled trial in pregnant women ( ≤26 gestational weeks ) in PNG . Sulphadoxine-pyrimethamine ( 1,500/75 mg ) plus azithromycin ( 1 g twice daily for 2 days ) ( SPAZ ) monthly from second trimester ( intervention ) was compared against sulphadoxine-pyrimethamine and chloroquine ( 450 to 600 mg , daily for three days ) ( SPCQ ) given once , followed by SPCQ placebo ( control ) . Women were assigned to treatment ( 1:1 ) using a r and omisation sequence with block sizes of 32 . Participants were blinded to assignments . The primary outcome was LBW . Analysis was by intention-to-treat . Results Of 2,793 women r and omised , 2,021 ( 72.4 % ) were included in the primary outcome analysis ( SPCQ : 1,008 ; SPAZ : 1,013 ) . The prevalence of LBW was 15.1 % ( 305/2,021 ) . SPAZ reduced LBW ( risk ratio [ RR ] : 0.74 , 95 % CI : 0.60–0.91 , P = 0.005 ; absolute risk reduction ( ARR ) : 4.5 % , 95 % CI : 1.4–7.6 ; number needed to treat : 22 ) , and preterm delivery ( 0.62 , 95 % CI : 0.43–0.89 , P = 0.010 ) , and increased mean birthweight ( 41.9 g , 95 % CI : 0.2–83.6 , P = 0.049 ) . SPAZ reduced maternal parasitaemia ( RR : 0.57 , 95 % CI : 0.35–0.95 , P = 0.029 ) and active placental malaria ( 0.68 , 95 % CI : 0.47–0.98 , P = 0.037 ) , and reduced carriage of gonorrhoea ( 0.66 , 95 % CI : 0.44–0.99 , P = 0.041 ) at second visit . There were no treatment-related serious adverse events ( SAEs ) , and the number of SAEs ( intervention 13.1 % [ 181/1,378 ] , control 12.7 % [ 174/1,374 ] , P = 0.712 ) and AEs ( intervention 10.5 % [ 144/1,378 ] , control 10.8 % [ 149/1,374 ] , P = 0.737 ) was similar . A major limitation of the study was the high loss to follow-up for birthweight . Conclusions SPAZ was efficacious and safe in reducing LBW , possibly acting through multiple mechanisms including the effect on malaria and on sexually transmitted infections . The efficacy of SPAZ in the presence of resistant parasites and the contribution of AZ to bacterial antibiotic resistance require further study . The ability of SPAZ to improve pregnancy outcomes warrants further evaluation . Trial registration Clinical Trials.gov NCT01136850 ( 06 April 2010 ) Because sub clinical genital tract infection may play a major role in preterm birth , the efficacy of adjunctive antibiotic therapy in combination with st and ard parenteral tocolysis was examined in a r and omized , blinded study of patients with idiopathic preterm labor . Labor was documented by three contractions in 20 minutes , cervical dilation of 1 cm or more , and the need for parenteral tocolysis . Enrollment was restricted to patients with intact membranes and without known causes for preterm labor . One hundred three patients at 24–34 weeks ' gestation were r and omized to intravenous ampicillin plus oral erythromycin or corresponding placebos . Compared with the placebo group , the adjunctive antibiotic group had a similar frequency of preterm birth ( 38 versus 44 % ) , time to delivery ( 34 versus 34 days ) , birth weight ( 2847 versus 2855 g ) , and episodes of recurrent labor requiring parenteral tocolysis ( 0.43 versus 0.49 ) . In our population , we found no benefit to the adjunctive use of ampicillin plus erythromycin . Significant differences in genital microflora between our patients and those of other studies may explain our results Low birth-weight is a leading health problem in developing countries . In a r and omized controlled trial , the effect of antimicrobials in pregnant women on improving birth-weight and duration of gestation was evaluated . Two hundred twenty-four pregnant women in their second trimester were r and omized to receive metronidazole ( 200 mg 3 times daily for 7 days ) and cephalexin ( 500 mg twice daily for 5 days ) orally by one group . The mean ( + /-SD ) birth-weights were 2,545 g ( + /-374 ) and 2584 g ( + /-358 , p=0.51 ) , the low birth-weight rates ( < 2.5 kg ) were 40 % and 36 % ( p = 0.28 ) , and the prematurity rates were 8 % and 11 % ( p = 0.6 ) in the treated group and the control group respectively . Due to small sample size , it is cautiously concluded that routine antimicrobials for genital and urinary tract infections of pregnant women do not improve birth-weight or duration of gestation . Rather an unexpected observation was the proportion requiring caesarian section or forceps , which was five-fold higher in the treated group ( p = 0.001 ) , and given no plausible explanations , this finding needs confirmation . Stunted mothers ( < 25th centile or 146.4 cm ) had two-fold higher risk for low birth-weight ( p = 0.04 ) and assisted delivery ( p = 0.1 ) . Low maternal body mass index ( < 25th centile or 18 ) had six-fold higher risk for stillbirth or abortion ( p = 0.007 ) , and high body mass index ( > 75th centile or 21.2 ) had three-fold higher risk for assisted delivery ( p = 0.003 ) OBJECTIVE The purpose of this study was to assess the association of presumptive Trichomonas vaginalis treatment during pregnancy and birth outcomes . STUDY DESIGN A community-r and omized trial of presumptive sexually transmitted disease treatment during pregnancy was conducted between 1994 and 1999 in Rakai district , Ug and a. A sub analysis of a trial of presumptive therapy with azithromycin , cefixime , and metronidazole assessed Trichomonas vaginalis treatment in pregnant women . RESULTS Children of 94 women with Trichomonas who were treated had increased low birth weight ( relative risk , 2.49 ; 95 % CI , 1.12 - 5.50 ) , preterm birth rate ( relative risk , 1.28 ; 95 % CI , 0.81 - 2.02 ) , and 2-year mortality rate ( relative risk , 1.58 ; 95 % CI , 0.99 - 2.52 ) , compared with children of 112 women with Trichomonas who were not treated . CONCLUSION Treatment of Trichomonas vaginalis during pregnancy may be deleterious , and we infer that this may be due to metronidazole . This is consistent with a National Institute for Child Health and Human Development trial that found an excess of preterm births in children of women with Trichomonas vaginalis infection who were treated with metronidazole BACKGROUND Pregnant women with bacterial vaginosis may be at increased risk for preterm delivery . We investigated whether treatment with metronidazole and erythromycin during the second trimester would lower the incidence of delivery before 37 weeks ' gestation . METHODS In 624 pregnant women at risk for delivering prematurely , vaginal and cervical cultures and other laboratory tests for bacterial vaginosis were performed at a mean of 22.9 weeks ' gestation . We then performed a 2:1 double-blind r and omization to treatment with metronidazole and erythromycin ( 433 women ) or placebo ( 191 women ) . After treatment , the vaginal and cervical tests were repeated and a second course of treatment was given to women who had bacterial vaginosis at that time ( a mean of 27.6 weeks ' gestation ) . RESULTS A total of 178 women ( 29 percent ) delivered infants at less than 37 weeks ' gestation . Eight women were lost to follow-up . In the remaining population , 110 of the 426 women assigned to metronidazole and erythromycin ( 26 percent ) delivered prematurely , as compared with 68 of the 190 assigned to placebo ( 36 percent , P = 0.01 ) . However , the association between the study treatment and lower rates of prematurity was observed only among the 258 women who had bacterial vaginosis ( rate of preterm delivery , 31 percent with treatment vs. 49 percent with placebo ; P = 0.006 ) . Of the 358 women who did not have bacterial vaginosis when initially examined , 22 percent of those assigned to metronidazole and erythromycin and 25 percent of those assigned to placebo delivered prematurely ( P = 0.55 ) . The lower rate of preterm delivery among the women with bacterial vaginosis who were assigned to the study treatment was observed both in women at risk because of previous preterm delivery ( preterm delivery in the treatment group , 39 percent ; and in the placebo group , 57 percent ; P = 0.02 ) and in women who weighed less than 50 kg before pregnancy ( preterm delivery in the treatment group , 14 percent ; and in the placebo group , 33 percent ; P = 0.04 ) . CONCLUSIONS Treatment with metronidazole and erythromycin reduced rates of premature delivery in women with bacterial vaginosis and an increased risk for preterm delivery OBJECTIVE The purpose of this study was to determine the impact of persistent bacterial vaginosis ( BV ) on the occurrence of spontaneous preterm birth ( SPB ) in women who test positive for fetal fibronectin . STUDY DESIGN This is a secondary analysis of a subset of pregnant women who tested positive for BV and fetal fibronectin between 16(0/7 ) and 25(6/7 ) weeks of gestation and who participated in r and omized placebo controlled trials of antibiotic therapy . Nugent 's criteria were used for the diagnosis of BV . Patients were reassessed for the presence of BV after treatment . The rate of SPB at < 34 weeks of gestation was analyzed on the basis of treatment mode and BV status at the follow-up visit . RESULTS The primary studies included a total of 3285 women . A subset of 215 women met the criteria for this analysis . Seventy-seven of 100 patients ( 77 % ) in the antibiotics group vs 33 of the 115 patients ( 28.7 % ) in the placebo group became BV negative ( P < .0001 ) . The rate of SPB at < 34 weeks of gestation was lower for BV resolution compared with persistent BV ( 0 vs 5.7 % , respectively ; P = .01 ) . CONCLUSION In women who tested positive for fetal fibronectin and BV , resolution of BV is associated with less SPB before 34 weeks of gestation BACKGROUND The ORACLE II trial compared the use of erythromycin and /or amoxicillin-clavulanate ( co-amoxiclav ) with that of placebo for women in spontaneous preterm labour and intact membranes , without overt signs of clinical infection , by use of a factorial r and omised design . The aim of the present study --the ORACLE Children Study II -- was to determine the long-term effects on children after exposure to antibiotics in this clinical situation . METHODS We assessed children at age 7 years born to the 4221 women who had completed the ORACLE II study and who were eligible for follow-up with a structured parental question naire to assess the child 's health status . Functional impairment was defined as the presence of any level of functional impairment ( severe , moderate , or mild ) derived from the mark III Multi-Attribute Health Status classification system . Educational outcomes were assessed with national curriculum test results for children resident in Engl and . FINDINGS Outcome was determined for 3196 ( 71 % ) eligible children . Overall , a greater proportion of children whose mothers had been prescribed erythromycin , with or without co-amoxiclav , had any functional impairment than did those whose mothers had received no erythromycin ( 658 [ 42.3 % ] of 1554 children vs 574 [ 38.3 % ] of 1498 ; odds ratio 1.18 , 95 % CI 1.02 - 1.37 ) . Co-amoxiclav ( with or without erythromycin Output:	Regarding the route of antibiotic administration , vaginal antibiotic prophylaxis during pregnancy did not prevent infectious pregnancy outcomes . Antibiotic prophylaxis did not reduce the risk of preterm prelabour rupture of membranes or preterm delivery ( apart from in the subgroup of women with a previous preterm birth who had bacterial vaginosis ) . Antibiotic prophylaxis given during the second or third trimester of pregnancy reduced the risk of postpartum endometritis , term pregnancy with pre-labour rupture of membranes and gonococcal infection when given routinely to all pregnant women . Therefore , we conclude that there is not enough evidence to support the use of routine antibiotics during pregnancy to prevent infectious adverse effects on pregnancy outcomes
MS21328	*TASK* the task is to summarize an input biomedical literature in six sentences *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 estimate the prevalence of wounds managed by the UK 's National Health Service ( NHS ) in 2012/2013 and the annual levels of healthcare re source use attributable to their management and corresponding costs . Methods This was a retrospective cohort analysis of the records of patients in The Health Improvement Network ( THIN ) Data base . Records of 1000 adult patients who had a wound in 2012/2013 ( cases ) were r and omly selected and matched with 1000 patients with no history of a wound ( controls ) . Patients ’ characteristics , wound-related health outcomes and all healthcare re source use were quantified and the total NHS cost of patient management was estimated at 2013/2014 prices . Results Patients ’ mean age was 69.0 years and 45 % were male . 76 % of patients presented with a new wound in the study year and 61 % of wounds healed during the study year . Nutritional deficiency ( OR 0.53 ; p<0.001 ) and diabetes ( OR 0.65 ; p<0.001 ) were independent risk factors for non-healing . There were an estimated 2.2 million wounds managed by the NHS in 2012/2013 . Annual levels of re source use attributable to managing these wounds and associated comorbidities included 18.6 million practice nurse visits , 10.9 million community nurse visits , 7.7 million GP visits and 3.4 million hospital outpatient visits . The annual NHS cost of managing these wounds and associated comorbidities was £ 5.3 billion . This was reduced to between £ 5.1 and £ 4.5 billion after adjusting for comorbidities . Conclusions Real world evidence highlights wound management is predominantly a nurse-led discipline . Approximately 30 % of wounds lacked a differential diagnosis , indicative of practical difficulties experienced by non-specialist clinicians . Wounds impose a substantial health economic burden on the UK 's NHS , comparable to that of managing obesity ( £ 5.0 billion ) . Clinical and economic benefits could accrue from improved systems of care and an increased awareness of the impact that wounds impose on patients and the NHS Leg ulcers are a chronic manifestation of sickle-cell disease ( SCD ) and are often painful , disabling , and difficult to treat . RGD peptide matrix treatment is a novel therapy design ed to provide a topical synthetic extracellular matrix that can act as a temporary substitute for the damaged natural matrix at the ulcer site . In this r and omized , placebo-controlled , double-blind , prospect i ve , multicenter investigation , SCD patients with full-thickness leg ulcers were treated with st and ard therapy plus RGD peptide matrix or saline placebo once weekly for up to 10 weeks . Healing in patients with chronic ulcers ( 2 months or greater in duration ) was significantly accelerated ( P = .0085 ) in RGD peptide matrix recipients compared with the placebo group . In these chronic ulcer cases , the average percent ulcer closure ( decrease in ulcer surface area ) in the RGD peptide matrix group ( 54.4 % + /- 8.9 % ) exceeded that in the placebo group ( 19.0 % + /- 24.3 % ) nearly threefold by study endpoint . Furthermore , RGD peptide matrix was equally effective in promoting healing of long persistent ulcers and ulcers of shorter duration . In contrast , st and ard therapy plus placebo was significantly less effective ( P = .001 ) in promoting healing for ulcers of progressively greater duration . The results of this study provide preliminary evidence that RGD peptide matrix treatment may significantly accelerate healing of chronic sickle-cell leg ulcers OBJECTIVE Comparison of desloughing efficacy after four weeks and healing outcomes after 12 weeks in sloughy venous leg ulcers treated with Manuka honey ( Woundcare 18 + ) vs. st and ard hydrogel therapy ( IntraSite Gel ) . BACKGROUND Expert opinion suggests that Manuka honey is effective as a desloughing agent but clinical evidence in the form of a r and omised controlled trial is not available . There is a paucity of research which uses Manuka honey in venous ulcers . DESIGN Prospect i ve , multicentre , open label r and omised controlled trial . METHOD R and omisation was via remote telephone . One hundred and eight patients with venous leg ulcers having > or=50 % wound area covered in slough , not taking antibiotics or immunosuppressant therapy were recruited from vascular centres , acute and community care hospitals and leg ulcer clinics . The efficacy of WoundCare 18 + to deslough the wounds after four weeks and its impact on healing after 12 weeks when compared with IntraSite Gel control was determined . Treatment was applied weekly for four weeks and follow-up was made at week 12 . RESULTS At week 4 , mean % reduction in slough was 67 % WoundCare 18 + vs. 52.9 % IntraSite Gel ( p = 0.054 ) . Mean wound area covered in slough reduced to 29 % and 43 % , respectively ( p = 0.065 ) . Median reduction in wound size was 34 % vs. 13 % ( p = 0.001 ) . At 12 weeks , 44 % vs. 33 % healed ( p = 0.037 ) . Wounds having > 50 % reduction in slough had greater probability of healing at week 12 ( 95 % confidence interval 1.12 , 9.7 ; risk ratio 3.3 ; p = 0.029 ) . Infection developed in 6 of the WoundCare 18 + group vs. 12 in the IntraSite Gel group . CONCLUSION The WoundCare 18 + group had increased incidence of healing , effective desloughing and a lower incidence of infection than the control . Manuka honey has therapeutic value and further research is required to examine its use in other wound aetiologies . RELEVANCE TO CLINICAL PRACTICE This study confirms that Manuka honey may be considered by clinicians for use in sloughy venous ulcers . Additionally , effective desloughing significantly improves healing outcomes Summary .— The results of a double‐blind trial of zinc sulphate in patients with chronic venous leg ulceration are reported . No significantly increased rate of healing was observed in the zinc‐treated group In order to assess the reported efficacy of natural honey in the healing of chronic ulcers , the efficacy of locally applied natural honey was compared to that of Eusol solution in an open trial involving 20 patients with sickle cell anaemia ( SS ) who were in steady clinical states and had chronic leg ulceration . All patients were admitted to hospital for the 4 week duration of the trial for bed rest , daily aseptic dressings , and weekly measurement of the size of the ulcer . Fifteen patients with a total of 19 leg ulcers were evaluable at the end of the trial . Eleven ulcers were dressed with honey while 8 were dressed with Eusol . No significant differences were found in rates of healing of the ulcers in either treatment groups . This trial does not support the suggestion that natural honey is superior to Eusol in the healing of chronic sickle cell leg ulceration A double-blind , placebo-controlled study was carried out in 12 patients suffering from chronic venous insufficiency and persistent leg ulcers to assess the efficacy of pentoxifylline treatment as an adjunct to compression b and aging in the conservative management of venous leg ulcers . Six patients were allocated at r and om to receive twice-daily infusions of 200 mg pentoxifylline intravenously and 400 mg pentoxifylline orally 3-times daily for 7 days then 400 mg oral doses 3-times daily for a further 60 days . The control group received matching placebo in an identical regimen . Treatment outcome was assessed by changes between the start and end of the study in venous ulcer surface area , and continuous wave Doppler ultrasound was used to monitor ankle/arm systolic pressure ratio , venous pressure at the ankle , valvular competence and possible venous reflux at intervals throughout the study period . The results showed that in the patients treated with pentoxifylline complete ulcer healing took place in 4 out of 6 and there was a significant reduction in mean ulcer surface area . In the control group , complete ulcer healing was recorded in 1 out of 6 patient only and the ulcer area was only moderately reduced in the others . There was no statistically significant differences between the two groups in the variables monitored by Doppler ultrasound but the difference between treatment outcome was significant . Treatment was well-tolerated Abstract Objective : To determine whether pentoxifylline 400 mg ( Trental 400 ) taken orally three times daily , in addition to ambulatory compression b and ages and dressings , improves the healing rate of pure venous ulcers . Design : R and omised , double blind placebo controlled trial , parallel group study of factorial design , permitting the simultaneous evaluation of alternative pharmaceutical , b and aging , and dressings material s. Setting : Leg ulcer clinics of a teaching and a district general hospital in southern Scotl and . Participants : 200 patients with confirmed venous ulcers and in whom other major causal factors were excluded . Interventions : Pentoxifylline 400 mg three times daily or placebo . Main outcome measure : Complete healing ( full epithelialisation ) of all ulcers on the trial leg . Results : Complete healing occurred in 65 of the 101 ( 64 % ) patients receiving pentoxifylline and 52 of the 99 ( 53 % ) patients receiving placebo . Conclusions : The difference in the healing rates between patients taking pentoxifylline and those taking placebo did not reach statistical significance . Key messages Leg ulcers cost the NHS around £ 400 million per annum 50%-75 % of venous leg ulcers can be succesfully treated with dressings and compression b and ages but take many months to heal A drug that reduced the healing time of venous ulcers would be useful , although no agent has been proved to be effective to date Trials with pentoxifylline , a vasoactive drug used in the treatment of peripheral vascular diseases , as an adjunct to the treatment of venous ulcers have been inconclusive At the 5 % level , pentoxifylline had a non-significant effect on healing rates of pure venous AIM Epidemiological data show that st and ard compression therapy for leg ulceration in chronic venous insufficiency ( CVI ) often fails to effectively improve patients ' condition . This study assesses the contribution of Daflon 500 mg added to conventional therapy in the healing of hypostatic ulcers of CVI patients . METHODS Patients of about 65 years were included , with ulcers > or = 2 and > or = 10 cm diameter on 1 or 2 limbs , Doppler ankle/arm pressure index > 0.9 , and no recent history of skin graft . Controls ( n=68 ) remained on compression alone while the tested group ( n=82 ) also received Daflon 500 mg 2 tablets/day during 6 months . Treatment could be stopped as soon as the reference ulcer appeared fully healed . Primary endpoints were the rate of healed ulcers and the time to complete healing assessed by planimetry/photography and clinical examination . Variations of the ulcer surface , appearance of the skin , and clinical symptoms of CVI were the secondary criteria . RESULTS Only 7 % of Daflon 500 mg patients necessitated the full 6 month therapy . Whatever the lesion size , from W8 significantly more healed ulcers were observed under Daflon 500 mg ( p=0.004 ) , and the ulcer surface was more reduced ( p=0.012 ) . For large ulcers , the rate of healing was approximately 2-fold higher with Daflon 500 mg , and the percentage of ulcers healed before W24 was significantly higher ( p=0.008 ) . Heavy leg sensation was significantly improved by Daflon 500 mg from W4 ( p < 0.05 ) . No treatment-related side effects were reported and the acceptability was considered excellent by 85 % of Daflon 500 mg patients . CONCLUSION Six months of Daflon 500 mg in addition to compression significantly improve some clinical symptoms and accelerate the healing process in patients with ulcerous complications of CVI , with a good acceptability We performed a r and omized , double‐blind study of the efficacy of locally applied zinc oxide on the healing of leg ulcers . Thirty‐seven geriatric patients , nineteen with arterial and eighteen with venous leg ulcers , were treated either with a gauze compress medicated with zinc oxide ( 400 μg ZnO/cm2 ) or with an identical compress without zinc oxide . The treatment was assessed from ulcer size measurements and the presence or abscncc of granulation and ulcer debridement over a period of 8 weeks . The zinc‐treated patients ( 83 % success rate ) responded significantly better ( P < 0·05 ) than the placebo‐treated patients ( 42 % success rate ) . The results suggest that healing of leg ulcers is improved after the addition of zinc oxide to the local regimen Several small studies have indicated that the systemic administration of pentoxifylline may accelerate healing of venous leg ulcers . The goal of this study was to further evaluate these findings in a larger scale placebo controlled trial and to explore the effect of the dose of pentoxifylline on healing . The study used a prospect i ve , r and omized , double-blind , parallel group placebo controlled design in a multicenter outpatient setting . Patients with one or more venous ulcer were enrolled , with all patients receiving st and ardized compression b and aging for treatment for their ulcers . Patients were Output:	These data permit the inferences that nutritional supplementation in the population s studied showed significant benefits in the healing of venous ulcers and tendency ( nonsignificant trends ) in the healing of diabetic and sickle cell ulcers
MS21329	*TASK* the task is to summarize an input biomedical literature in six sentences *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 examined 6-month treatment outcomes among 428 cocaine-dependent out patients with ( n = 34 ) and without ( n = 394 ) posttraumatic stress disorder ( PTSD ) in a r and omized controlled multisite clinical trial of manual-based psychotherapies for substance use disorder ( SUD ) . METHOD Assessment s were completed at baseline and monthly during the 6-month treatment . With longitudinal mixed-effects models , we compared outcomes between SUD-PTSD and SUD-only patients and also examined rates of within-group change . RESULTS Results indicated a highly consistent pattern : the SUD-PTSD patients were more impaired to begin with and remained so across time compared with SUD-only patients ( with the exception of substance use and addiction-related legal and employment problems , which did not differ between groups ) . Also , the SUD-PTSD patients improved less than SUD-only patients in alcohol use and the majority of addiction-related psychosocial problems . However , the two groups did not differ significantly in improvement over time on drug use or global psychological severity . CONCLUSIONS The greater impairment and relative lack of improvement of SUD-PTSD patients , compared with those with SUD-only , suggest a need for dual-diagnosis treatments that more directly target their areas of difficulty OBJECTIVE This study examined the prevalence of lifetime traumatic events and current symptoms of posttraumatic stress disorder ( PTSD ) among treatment-seeking cocaine-dependent out patients and compared patients with and without PTSD on current substance use , psychopathology , and sociodemographic characteristics . METHOD The subjects were 122 adult cocaine-dependent out patients participating in a treatment outcome study of psychosocial therapy . In addition to st and ard self-report and interview measures of psychopathology and substance use , the subjects completed the Trauma History Question naire and the PTSD Checklist before entering treatment . RESULTS These patients experienced a large number of lifetime traumatic events ( mean = 5.7 ) ; men experienced more general disasters and crime-related traumas than women , and women experienced more physical and sexual abuse than men . According to self-report measures , 20.5 % of the subjects currently met the DSM-III-R criteria for PTSD ; the rate of PTSD was 30.2 % among women and 15.2 % among men . Patients with PTSD had significantly higher rates of co-occurring axis I and axis II disorders , interpersonal problems , medical problems , resistance to treatment , and psychopathology symptoms than patients without PTSD . Psychopathology symptoms represented the most consistent difference between the two groups and provided the best prediction of PTSD status in a logistic regression . However , the groups did not differ significantly in current substance use or sociodemographic characteristics . CONCLUSIONS These findings underscore the value of screening substance abusers for PTSD , because it can identify a small but substantial number who might require additional treatment . Further studies of the relationship between PTSD and substance abuse appear warranted 424 BMJ \| 24 FEBRUARY 2007 \| VOLUME 334 Almost all studies have some missing observations . Yet textbooks and software commonly assume that data are complete , and the topic of how to h and le missing data is not often discussed outside statistics journals . There are many types of missing data and different reasons for data being missing . Both issues affect the analysis . Some examples are : ( 1 ) In a postal question naire survey not all the selected individuals respond ; ( 2 ) In a r and omised trial some patients are lost to follow-up before the end of the study ; ( 3 ) In a multicentre study some centres do not measure a particular variable ; ( 4 ) In a study in which patients are assessed frequently some data are missing at some time points for unknown reasons ; ( 5 ) Occasional data values for a variable are missing because some equipment failed ; ( 6 ) Some laboratory sample s are lost in transit or technically unsatisfactory ; ( 7 ) In a magnetic resonance imaging study some very obese patients are excluded as they are too large for the machine ; ( 8) In a study assessing quality of life some patients die during the follow-up period The present study evaluated whether Posttraumatic Stress Disorder ( PTSD ) symptom severity was associated with participation and treatment outcomes comparing a Vipassana meditation course to treatment as usual in an incarcerated sample . This study utilizes secondary data . The original study demonstrated that Vipassana meditation is associated with reductions in substance use . The present study found that PTSD symptom severity did not differ significantly between those who did and did not volunteer to take the course . Participation in the Vipassana course was associated with significantly greater reductions in substance use than treatment as usual , regardless of PTSD symptom severity levels . These results suggest that Vipassana meditation is worthy of further study for those with comorbid PTSD and substance use problems The present study investigates the prevalence of comorbid posttraumatic stress disorder ( PTSD ) in a sample of Polish alcohol dependent patients and examines the relationship between comorbid PTSD and alcohol use-related problems . Patients ( n=458 ) were recruited from r and omly chosen clinical setting s and were administered self-report measures of trauma exposure , PTSD symptomatology , and alcohol use-related problems . From this sample , 67 % of the patients reported having experienced at least one criterion A traumatic event , and 60 % of them reported multiple traumas . Approximately 25 % of them met the criteria for current PTSD . The only significant difference between the PTSD and non-PTSD groups was abuse/dependence of other psychoactive substances . However , patients reporting physical assaults committed by a non-stranger reported more frequent PTSD diagnosis , more extensive symptomatology , more conflicts with the law and more physical injuries due to drinking . The findings of the study confirm the importance of assessing trauma and PTSD in alcohol dependent patients Psychological trauma and post-traumatic stress disorder ( PTSD ) may complicate and reduce the effectiveness of treatment for substance use disorders ( SUDs ) . This study assessed trauma history and symptoms of simple and complex PTSD at baseline in a r and omized trial of contingency management ( CM ) compared to st and ard treatment ( ST ) with 142 cocaine- or heroin-dependent out patients . History of exposure to each of eight types of psychological trauma was unrelated to treatment outcome , except for witnessed assaults and emotional abuse . Complex PTSD symptoms were inversely associated with short-term treatment outcomes , and PTSD symptoms were positively related to long-term outcome , independent of the effects of demographics , psychological distress , baseline substance use status , and treatment modality . Complex PTSD symptoms warrant further study as a potential negative prognostic factor in SUD interventions AIMS To assess the utility of biological testing in a general population survey for estimating prevalence and evaluating self-report data quality . DESIGN An audio computer-assisted interview was administered to subjects from June 2001 to January 2002 . Immediately following the interview , subjects were requested to participate in hair , oral fluid and urine testing . SETTING Subjects were from r and omly selected households in the City of Chicago using multi-stage sampling methods . Interviews were conducted in subjects ' homes . PARTICIPANTS The data represent 627 r and omly selected adult participants , ages 18 - 40 years . MEASUREMENTS Prevalance , kappa , conditioned kappa , sensitivity , specificity , under-reporting , ' mixed model ' and logistic regression . FINDINGS Higher rates of marijuana use were generated from survey reports than from drug testing . Drug testing generated higher prevalence rates than survey reports for recent use of cocaine and heroin . Under-reporting of recent drug use was apparent for all three substances . Sensitivity was particularly low for cocaine and heroin . Race was related to under-reporting , with African Americans less likely to report marijuana use despite a positive test result . CONCLUSIONS The utility of drug testing for surveys depends on the type of substance examined as well as on the type of test employed . Multiple tests have more utility than a single test . Drug testing is useful for identifying the levels and sources of under-reporting in a survey and provides a basis for adjusting prevalence estimates based on self-reports This study examined concurrent and prospect i ve associations between substance use disorder ( SUD ) and posttraumatic stress disorder ( PTSD ) diagnosis and symptoms and mechanisms underlying these associations . Participants ( n = 133 ) were assessed at intake and 6 months following inpatient SUD treatment . Patients differed by baseline PTSD status on psychiatric comorbidity and substance use history but not on current substance use symptoms . Participants with alcohol use disorders reported a greater number of reexperiencing symptoms . Baseline PTSD status did not predict substance use outcome . However , change in PTSD status over follow-up predicted substance use outcomes ; those with unremitted PTSD demonstrated poorer SUD outcome than those with remitted PTSD . General psychiatric distress at follow-up was associated with poorer outcomes , and such distress mediated the association between PTSD change status and substance use outcome . Findings suggest that clinicians should assess for PTSD among those with SUD and , during treatment , should monitor PTSD and other psychological symptoms , which may be risk factors for relapse to substance abuse Objective To present lifetime rates of service use for psychological and substance use related problems among regular substance users and to examine factors associated with service use . Method Data come from a prospect ive-longitudinal , epidemiological study of a community sample of adolescents and young adults ( n = 2548 , age 14–24 years at baseline ) in Munich , Germany . The Munich-Composite International Diagnostic Interview ( M-CIDI ) was used at baseline and at two follow-ups to assess substance use and service use . Results Cumulated lifetime incidence of any substance abuse or dependence was 43.7 % . Of those with abuse and dependence 23 % had ever used any services for psychological or substance use related problems . Illicit substance users especially those with dependence had the highest rates of lifetime service use ( 52.1 % ) . Psychotherapists and counseling services were contacted most frequently among regular substance users over their lifetimes . Utlilisation rates of substance abuse services were low ( 2 % ) . Comorbid anxiety disorders and distressing life events were associated with increased lifetime service use . Conclusions Only a minority of adolescents and young adults with substance use disorders have ever sought professional help . Specialized substance abuse services play only a minor role . The core role of psychotherapists and non-substance abuse specialized services needs critical research attention . Linkages between psychotherapists and the substance use service system should be strengthened to detect and intervene at early developmental stages of abuse and dependence BACKGROUND Although disulfiram and naltrexone have been approved by the Food and Drug Administration for the treatment of alcoholism , the effect of these medications on alcohol use outcomes and on psychiatric symptoms is still unknown in patients with co-occurring disorders post-traumatic stress disorder ( PTSD ) . METHODS Patients ( n = 254 ) with a major Axis I psychiatric disorder and comorbid alcohol dependence were treated for 12 weeks in a medication study at three Veterans Administration outpatient clinics . R and omization included ( 1 ) open r and omization to disulfiram or no disulfiram ; and ( 2 ) double-blind r and omization to naltrexone or placebo . This result ed in four groups : ( 1 ) naltrexone alone ; ( 2 ) placebo alone ; ( 3 ) disulfiram and naltrexone ; or ( 4 ) disulfiram and placebo . Outcomes were measures of alcohol use , PTSD symptoms , alcohol craving , GGT levels and adverse events . RESULTS 93 individuals ( 36.6 % ) met DSM-IV criteria for PTSD . Subjects with PTSD had better alcohol outcomes with active medication ( naltrexone , disulfiram or the combination ) than they did on placebo ; overall psychiatric symptoms of PTSD improved . Individuals with PTSD were more likely to report some side effects when treated with the combination . CONCLUSIONS The results of this study suggest that disulfiram and naltrexone are effective and safe for individuals with PTSD and comorbid alcohol dependence OBJECTIVE The purpose of this study was to determine whether opioid-dependent patients with diagnosed posttraumatic stress disorder ( PTSD ) have poorer long-term outcomes in opioid substitution treatment than do patients without PTSD . METHOD This prospect i ve observational study examined outcomes of 255 opioid-dependent patients ( men = 248 ) entering opioid substitution treatment at eight clinics in the Veterans Health Administration ( VHA ) . Subjects were interviewed at treatment entry , 6 months , and 1 year about substance use and related problems , health status , treatment satisfaction , and non-VHA health care utilization . Medical records were review ed to obtain toxicology results , health care utilization data , and diagnoses . Medical record review identified a diagnosis of PTSD in 71 ( 28 % ) patients . Substance-use and mental-health outcomes and health care utilization in the first year following treatment entry were compared between patients with and without a diagnosis of PTSD . RESULTS Patients with and without PTSD had similar treatment responses . Although patients with PTSD had longer histories of drug use at intake , at 1-year follow-up they showed reductions in heroin , cocaine , and alcohol use , comparable to patients without the disorder . PTSD patients received higher doses of opiate medication , attended more psychosocial treatment sessions for substance-use disorder , and had better treatment retention . Psychiatric symptoms for patients with PTSD were more severe at intake and showed little improvement throughout treatment . CONCLUSIONS Opioid substitution therapy is as effective at reducing substance use in PTSD patients as it is in patients without the disorder , but additional services are needed for treatment of psychological problems that are Output:	Remarkably , no consistent indication of a negative effect of CO-PTSD on the reported SUD treatment outcome was found .
MS21330	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Anemia , one of the most common complications of cancer chemotherapy , has been managed with red blood cell ( RBC ) transfusions . As an alternative , the agent epoetin alfa has the potential to reduce the transfusion requirements of patients receiving cancer chemotherapy . To estimate the value that cancer patients place on the drug , an economic analysis using the concept of willingness to pay ( WTP ) was conducted Health-related quality of life ( HrQOL ) assessment s are gaining importance as outcome measures in cancer clinical trials . A recently published clinical trial reported statistically significant ( P<0.001 ) increases in haemoglobin ( Hb ) levels and significantly ( P<0.01 ) increased HrQOL scores following the administration of recombinant human erythropoietin ( r-HuEPO , epoetin alfa ) versus placebo to anaemic cancer patients who received non-platinum chemotherapy . This study employed five cancer-specific HrQOL instruments . Hb and HrQOL data from this trial were analysed to estimate the minimally important difference ( MID ) in HrQOL measures that could be interpreted as clinical ly meaningful , with Hb level selected as the best external st and ard . Patients were assigned to two groups : improved ( Hb increases of > /=1 g/dL ) or stable ( change in Hb of-1 g/dL to < 1 g/dL ) . The MID was first determined as the difference between the mean changes in HrQOL in the improved group versus the stable group . By this analysis , the differences in HrQOL scores between the epoetin alfa group and the placebo group were clinical ly important for all Hb-sensitive , cancer-specific HrQOL evaluations . Linear regression analyses performed to provide estimates of the MID for specific values of Hb change confirmed that the differences in HrQOL scores between patient groups were clinical ly significant . These analyses were repeated using a data set from a separate clinical trial , which further supported the conclusion that observed HrQOL changes demonstrated in the multicentre , double-blind study were clinical ly important . These methods provide one means for interpreting the clinical relevance of changes in HrQOL evaluated in clinical trials PURPOSE To determine whether weekly epoetin alfa could improve hemoglobin ( HgB ) levels , reduce RBC transfusions , and improve quality of life ( QOL ) in patients with advanced cancer and with anemia after receiving myelosuppressive chemotherapy . PATIENTS AND METHODS This double-blind , placebo-controlled study r and omly assigned patients to placebo or epoetin alfa ( Ortho Biotech , Bridgewater , NJ ) 40,000 U subcutaneous weekly for 16 weeks . QOL , HgB , and RBC transfusions were measured pretreatment and monthly . RESULTS The study accrued 344 patients ; 330 were assessable for efficacy and 305 were assessable for QOL . Placebo-treated patients had a mean increase in HgB of 0.9 g/dL ( range , -3.8 to + 5.3 ) compared with 2.8 g/dL ( range , -2.2 to + 7.5 ) for epoetin-treated patients ( P < .0001 ) . During the study , 31.7 % of placebo-treated patients achieved a > or = 2 g/dL HgB increase compared with 72.7 % of epoetin-treated patients ( P < .0001 ) . The incidence of RBC transfusion for placebo and epoetin treatment arms was 39.6 % and 25.3 % ( P = .005 ) , respectively . The placebo group received 256 units of RBCs compared with 127 units in the epoetin group ( P < .0001 ) . The incidence of toxicity in the groups was similar . Changes in the average QOL scores from baseline to the end of the study were similar in the two groups ( P = not significant ) . The HgB responders ( irrespective of treatment arm ) had a mean change in Functional Assessment of Cancer Therapy ( FACT ) fatigue score from a baseline of + 5.1 compared with -2.1 for the nonresponders ( P = .006 ) . CONCLUSION Epoetin alfa significantly improved HgB and reduced transfusions in this patient population . These results support the use of weekly epoetin alfa as an ameliorative agent for cancer-related anemia PURPOSE The efficacy and safety of darbepoetin alpha ( DA ) for treating patients with active cancer and anemia not receiving or planning to receive cytotoxic chemotherapy or myelosuppressive radiotherapy was evaluated . PATIENTS AND METHODS Patients with active cancer and anemia not receiving or planning to receive chemotherapy or radiotherapy were enrolled onto a phase III , multicenter , r and omized , placebo-controlled study and administered placebo or DA 6.75 microg/kg every 4 weeks ( Q4W ) for up to 16 weeks with a 2-year follow-up for survival . Patients who completed 16 weeks of treatment could receive the same treatment as r and omized Q4W for an additional 16 weeks . The primary end point was all occurrences of transfusions from weeks 5 through 17 ; safety end points included incidence of adverse events and survival . RESULTS The incidence of transfusions between weeks 5 and 17 was lower in the DA group but was not statistically significantly different from that of placebo . DA was associated with an increased incidence of cardiovascular and thromboembolic events and more deaths during the initial 16-week treatment period . Long-term survival data demonstrated statistically significantly poorer survival in patients treated with DA versus placebo ( P = .022 ) . This effect varied by baseline covariates including , sex , tumor type , and geographic region ; statistical significance diminished ( P = .12 ) when the analysis was adjusted for baseline imbalances or known prognostic factors . CONCLUSION DA was not associated with a statistically significant reduction in transfusions . Shorter survival was observed in the DA arm ; thus , this study does not support the use of erythropoiesis-stimulating agents in this subset of patients with anemia of cancer PURPOSE To determine whether maintaining HGB levels > or = 12.0 g/dL with recombinant human erythropoietin ( R-HUEPO ) compared to " st and ard " treatment ( transfusion for HGB < or = 10.0 g/dL ) improves progression-free survival ( PFS ) , overall survival ( OS ) and local control ( LC ) in women receiving concurrent weekly cisplatin and radiation ( CT/RT ) for carcinoma of the cervix . In addition , to determine whether platinum-DNA adducts were associated with clinical characteristics or outcome . METHODS Patients with stage IIB-IVA cervical cancer and HGB < 14.0 g/dL were r and omly assigned to CT/RT+/-R-HUEPO ( 40,000 units s.c . weekly ) . R-HUEPO was stopped if HGB > 14.0 g/dL. Endpoints were PFS , OS and LC . Platinum-DNA adducts were quantified using immunocytochemistry assay in buccal cells . RESULTS Between 08/01 and 09/03 , 109 of 114 patients accrued were eligible . Fifty-two received CT/RT and 57 CT/RT+R-HUEPO . The study closed prematurely , with less than 25 % of the planned accrual , due to potential concerns for thromboembolic event ( TE ) with R-HUEPO . Median follow-up was 37 months ( range 9.8 - 50.4 months ) . PFS and OS at 3 years should be 65 % and 75 % for CT/RT and 58 % and 61 % for CT/RT+R-HUEPO , respectively . TE occurred in 4/52 receiving CT/RT and 11/57 with CT/RT+R-HUEPO , not all considered treatment related . No deaths occurred from TE . High-platinum adducts were associated with inferior PFS and LC . CONCLUSION TE is common in cervical cancer patients receiving CT/RT . Difference in TE rate between the two treatments was not statistically significant . The impact of maintaining HGB level > 12.0 g/dL on PFS , OS and LC remains undetermined Darbepoetin alfa is an erythropoiesis-stimulating agent ( ESA ) approved for treating chemotherapy-induced anemia . This phase II , double-blind , placebo-controlled study examined the efficacy of darbepoetin alfa for treating anemia of cancer ( AoC ) in patients not receiving chemotherapy or radiotherapy . Patients were r and omized 3:1 to receive darbepoetin alfa ( 6.75 microg/kg ) or placebo every 4 weeks ; the end of the study was at week 17 . The primary endpoint was the percentage of patients with a hematopoietic response . Secondary endpoints included transfusion incidence and safety parameters . Efficacy analyses were performed on 162 patients in the darbepoetin alfa group and 56 patients in the placebo group . The Kaplan-Meier percentages of patients who achieved a hematopoietic response ( darbepoetin alfa , 69 % ; placebo , 24 % ) or achieved the target hemoglobin ( darbepoetin alfa , 85 % ; placebo , 50 % ) differed significantly between treatment groups . The transfusion incidence did not differ between treatment groups probably because of the low baseline transfusion rates in AoC patients . The incidence of adverse events ( including on- study deaths ) was similar in both groups . In conclusion , darbepoetin alfa appeared to be well tolerated and significantly increased hemoglobin levels in these AoC study patients OBJECTIVES Mathematical modeling is used widely in economic evaluations of pharmaceuticals and other health-care technologies . Users of models in government and the private sector need to be able to evaluate the quality of models according to scientific criteria of good practice . This report describes the consensus of a task force convened to provide modelers with guidelines for conducting and reporting modeling studies . METHODS The task force was appointed with the advice and consent of the Board of Directors of ISPOR . Members were experienced developers or users of models , worked in academia and industry , and came from several countries in North America and Europe . The task force met on three occasions , conducted frequent correspondence and exchanges of drafts by electronic mail , and solicited comments on three drafts from a core group of external review ers and more broadly from the membership of ISPOR . RESULTS Criteria for assessing the quality of models fell into three areas : model structure , data used as inputs to models , and model validation . Several major themes cut across these areas . Models and their results should be represented as aids to decision making , not as statements of scientific fact ; therefore , it is inappropriate to dem and that models be vali date d prospect ively before use . However , model assumptions regarding causal structure and parameter estimates should be continually assessed against data , and models should be revised accordingly . Structural assumptions and parameter estimates should be reported clearly and explicitly , and opportunities for users to appreciate the conditional relationship between inputs and outputs should be provided through sensitivity analyses . CONCLUSIONS Model-based evaluations are a valuable re source for health-care decision makers . It is the responsibility of model developers to conduct modeling studies according to the best practicable st and ards of quality and to communicate results with adequate disclosure of assumptions and with the caveat that conclusions are conditional upon the assumptions and data on which the model is built Impaired cognition , fatigue , and diminished quality of life ( QOL ) are commonly associated with breast cancer chemotherapy . This r and omized , double-blind , placebo-controlled pilot trial assessed the feasibility of quantifying the effects of epoetin alfa on cognitive function and mood , and evaluated its effects on fatigue and QOL in patients with breast cancer treated with anthracycline-based adjuvant or neoadjuvant chemotherapy . Patients were r and omized to receive epoetin alfa 40,000 U subcutaneously once weekly or placebo at the beginning of 4 cycles of chemotherapy administered over 12 weeks . Cognitive function was assessed by Executive Interview ( EXIT25 ) and Clock Drawing Tasks ; mood by Profile of Mood States ; anemia-related symptoms , including fatigue , by the Functional Assessment of Cancer Therapy-Anemia ( FACT-An ) subscale ; and QOL by Linear Analog Scale Assessment . Ninety-four patients were evaluable for efficacy and safety . Mean change in EXIT25 scores from baseline to cycle 4 in the epoetin alfa group was 1.3 + /- 3.3 ; the mean change was 0.3 + /- 2.4 in the placebo group ( a negative change indicates improved executive function ) . There was no difference between groups in mean change in EXIT25 score from baseline to 6-month follow-up assessment . Mean hemoglobin levels were higher in the epoetin alfa group compared with the placebo group after 4 cycles of chemotherapy . Epoetin alfa recipients had less of a decrease in FACT-An subscale scores from baseline to cycle 4 and improvement in FACT-An subscale scores at 6-month follow-up assessment compared with placebo . Epoetin alfa therapy was well tolerated . These data suggest that epoetin alfa may have attenuated the cognitive impairment and fatigue that occurred during adjuvant breast cancer chemotherapy This r and omized , controlled trial evaluated the effect of darbepoetin alfa on hospitalization days , transfusion requirements , hemoglobin levels , and fatigue in patients with anemia of cancer ( AOC ) . Eligible patients were anemic ( hemoglobin < or=11 g/dl ) due to cancer , > or=18 years old , and had not received chemotherapy or radiotherapy within 4 weeks of study screening . Patients were r and omized 4:1 to receive darbepoetin alfa Output:	During a 1.3-year time horizon , ESA was associated with higher costs and worse clinical outcomes . Use of ESA for anemia related to cancer is associated with incremental cost-effectiveness ratios that are not economically attractive , even when used in a conservative fashion recommended by current guidelines
MS21331	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Onychomycosis is a prevalent infection of the nail caused primarily by dermatophytes . Fluconazole is active in vitro against the most common pathogens of onychomycosis , penetrates into the nail bed , and is clinical ly effective in the treatment of a wide variety of superficial fungal infections . OBJECTIVE The purpose of this study was to compare the efficacy and safety of three different doses of fluconazole ( 150 , 300 , and 450 mg ) given orally once weekly to that of placebo in the treatment of distal subungual onychomycosis of the toenail caused by dermatophytes . METHODS In this multicenter , double-blind study , 362 patients with mycologically confirmed onychomycosis were r and omized to treatment with fluconazole , 150 , 300 , or 450 mg once weekly , or placebo once weekly for a maximum of 12 months . To enter the study , patients were required to have at least 25 % involvement of the target nail with at least 2 mm of healthy nail from the nail fold to the proximal onychomycotic border . Patients who were clinical ly cured or improved at the end of treatment were further evaluated over a 6 month follow-up period . At both the end of therapy and the end of follow-up , clinical success of the target nail was defined as reduction of the affected area to less than 25 % or cure . RESULTS At the end of therapy , 86 % to 89 % of patients in the fluconazole treatment groups were judged clinical successes as defined above compared with 8 % of placebo-treated patients . Clinical cure ( completely healthy nail ) was achieved in 28 % to 36 % of fluconazole-treated patients compared with 3 % of placebo-treated patients . Fluconazole demonstrated mycologic eradication rates of 47 % to 62 % at the end of therapy compared with 14 % for placebo . The rates at the end of follow-up were very similar , indicating that eradication of the dermatophyte was maintained over the 6-month period . All efficacy measures for the fluconazole groups were significantly superior to placebo ( p=0.0001 ) ; there were no significant differences between the fluconazole groups on these efficacy measures . The clinical relapse rate among cured patients over 6 months of follow-up was low at 4 % . Fluconazole was well tolerated at all doses over the 12-month treatment period , with the incidence and severity of adverse events being similar between the fluconazole and placebo treatment groups . Mean time to clinical success in the fluconazole treatment groups was 6 to 7 months . This time frame may be used as a guideline for fluconazole treatment duration . CONCLUSION The results of this study support the use of fluconazole in the treatment of distal subungual onychomycosis of the toenail caused by dermatophytes . Doses between 150 to 450 mg weekly for 6 months were clinical ly and mycologically effective as well as safe and well tolerated In a multicentre , r and omised , double-blind , 48-week clinical trial , 118 patients with toe-nail onychomycosis were given terbinafine ( 250 mg daily ) or placebo for 12 weeks , followed by 12 weeks of observation . Non-responders were offered 12 further weeks of terbinafine ( 250 mg daily ) from week 28 . Each patient had 8 - 12 consecutive nail specimens collected from the same nail , allowing for an assessment of the fungal nail flora from 1,321 nail specimens . By week 48 , the overall mycological cure rate for terbinafine patients was 94 % . 64 % of patients had an underlying dermatophyte infection with at least 1 non-dermatophyte mould or yeast isolated from at least 1 specimen . These contaminants often overgrow or mask the presence of a dermatophyte . In only 2.5 % of all patients was the same non-dermatophyte isolated from 2 or more consecutive specimens , probably representing secondary colonisation which exploits nutrients released by the underlying dermatophyte . The presence of incidental non-dermatophyte contaminants or secondary colonisers did not affect treatment outcome , and in this study treatment of the primary dermatophyte pathogen with terbinafine cleared the nails from infection in all cases . 80 % of patients remained mycologically negative after 2 years BACKGROUND Current treatment of onychomycosis of the toenail is poor and relapse is common . OBJECTIVE Our purpose was to assess the efficacy and safety of oral terbinafine and placebo in onychomycosis of the toenail with the use of a novel treatment protocol . METHODS This was a r and omized , double-blind , 48-week study . Twelve weeks of terbinafine ( 250 mg daily ) or placebo was followed by 12 weeks of observation . Responders received no further treatment and nonresponders were offered 12 weeks of terbinafine ( 250 mg daily ) from week 28 . RESULTS Of 111 evaluable patients , 88 % ( 49 of 56 ) of the patients given terbinafine and 29 % ( 16 of 55 ) of the patients given placebo had a negative mycologic culture at week 24 ( p < 0.001 ) , 57 % ( 32 of 56 ) of the terbinafine group and 6 % ( 3 of 55 ) of the placebo group were responders ( p < 0.001 ) . By week 48 , after the terbinafine nonresponders were given a second 12-week course of terbinafine , the overall mycologic cure rate for the patients given terbinafine was 94 % . CONCLUSION High mycologic cure rates in onychomycosis of the toenail can be achieved by terbinafine by this novel treatment regimen BACKGROUND Griseofulvin has been used in the treatment of toenail onychomycosis with limited success . Evidence suggests that terbinafine may be more effective . OBJECTIVE In a double-blind , parallel-group study we compared 250 mg/day terbinafine for 16 weeks with 500 mg/day griseofulvin for 52 weeks ( or for shorter periods in cured patients ) in patients with toenail onychomycosis . METHODS Eighty-nine patients with culture-proved tinea unguium were included , and 43 in the terbinafine group and 41 in the griseofulvin group were assessable for efficacy . Patients who had not improved after 16 weeks were entered into an open study and were given 250 mg/day terbinafine for 16 weeks with the study code still blinded and were then followed up for 20 weeks . RESULTS Terbinafine was significantly more effective than griseofulvin , with 42 % being completely cured and 84 % mycologically cured compared with only 2 % with total cure and 45 % with mycologic cure in the griseofulvin-treated group . The number of side effects was significantly lower in the terbinafine group ( 11 % ) compared with the griseofulvin group ( 29 % ) . CONCLUSION Terbinafine is significantly more effective than griseofulvin in the treatment of toenail onychomycosis BACKGROUND Dermatophyte infections of the toenail have been difficult to treat , requiring long courses of therapy and having high recurrence rates . New oral antifungal agents with better outcomes and minimal adverse events are needed . OBJECTIVE The purpose of this study was to compare two newer antifungal compounds , terbinafine and itraconazole , for efficacy and safety in toenail onychomycosis caused by dermatophytes . METHODS The study was r and omized and double-blind . It compared 12 weeks of continuous oral treatment with terbinafine 250 mg/day or itraconazole 200 mg/day for confirmed toenail dermatophyte onychomycosis . Clinical symptoms and mycologic outcome were assessed at weeks 4 , 8 , 12 , 24 , 36 , and 48 . A total of 372 patients ( 186 in each group ) with dermatophyte infection confirmed by microscopy and culture were included in the intent-to-treat analysis . RESULTS At week 48 , a statistically significantly greater percentage of the terbinafine group than itraconazole group showed negative mycology ( 73 % [ 119 of 163 ] vs 45.8 % [ 77 of 168 ] ; p < 0.0001 ) ( difference = 27.2 % ; 95 % CI = [ 17.0 % , 37.3 % ] ) . The difference was also confirmed clinical ly ( p = 0.001 ) in the patients who were clinical ly cured or had only minimal symptoms at the end of the study ( 76.2 % [ 125 of 164 ] vs 58.1 % [ 100 of 172 ] ) ( difference = 18.1 % ; 95 % CI = [ 8.24 % , 27.9 % ] ) . The geometric mean length of healthy nail of the big toe was significantly greater in the terbinafine than itraconazole group ( 8.1 vs 6.4 mm ; p = 0.026 ) . Tolerability was good to very good in almost 90 % of patients in both groups , and all reported adverse events were known for these compounds . CONCLUSION Terbinafine produced higher rates of clinical and mycologic cure at follow-up than did itraconazole Toenail tinea is a very recalcitrant dermatosis . Griseofulvin at > or = 500 mg/day is the current medication of choice , but it is minimally successful . In a controlled open trial ultramicrosize griseofulvin ( UMSG ) at doses of 660 and 990 mg/day was compared with itraconazole at 100 mg/day in 109 patients . At 4-week intervals , the patients were evaluated for their clinical and mycological statuses and adverse reactions . Treatment was given for up to 18 months . Compliance was checked by tablet counting . Response ( cure , partial cure , marked improvement ) was analyzed by the intent-to-treat method . Cured and partially cured patients were followed up . Except for one early dropout , the toenails ( mean , 6 to 7 ) were involved . Cure or partial cure was found in 6 % ( UMSG at 660 mg ) , 14 % ( UMSG at 990 mg ) , and 19 % ( itraconazole at 100 mg ) of patients ( P = 0.2097 ) ; marked improvement was found in 36 , 44 , and 39 % of patients in the three treatment groups , respectively . Most patients had to be treated for 18 months . Failure was related to short medication periods ( adverse drug reactions , dropout ) . While stable cure was not obtained with UMSG at 660 mg , the higher dose of UMSG and itraconazole gave stable cures in the other patients . Side effects of nausea , diarrhea , and headache were found in 20 , 26 , and 11 patients , respectively ( P = 0.0028 ) , and the numbers in whom medication had to be discontinued differed , too ( P = 0.0137 ) . While there was no major difference with glutamic-pyruvic transaminase and gamma-GT , total and low-density lipoprotein cholesterol levels declined slightly in the itraconazole group ( P = 0.0357 and P = 0.0639 , respectively , at 3 months ) . More than 70 % of the patients had an average compliance of > or = 90 % ; four patients ( two dropouts ) were poor compliers . In conclusion , it appears question able whether griseofulvin can continue to be considered the " gold st and ard " in the treatment of toenail tinea . At present , itraconazole at 100 mg shows better efficacy and is better tolerated Lamisil ® ( terbinafine ) 250 mg daily and itraconazole 200 mg daily were compared in the treatment of dermalophyte toe onychomycosis over 12 weeks in a double‐blind r and omized clinical trial . At the end of follow‐up ( week 48 ) treatment with Lamisil ® led to negative mycology in 7 3 % of patients compared with 45–8 % in the itraconazole group ( P < 00001 ) , Globally the clinical symptoms of the target nail improved , a response which was in favour of Lamisil ® ( P=0·001 ) , The percentages of patients who were clinical ly totally cured or who presented with only minimal symptoms were 76′3 ' ) ( ) for the Lamisil ® ‐treated group compared with 58–1 % in the itraconazole group . The unaffected nail length for big toes was significantly higher in the Lamisil ® ‐treated group ( 9·1 mm vs , 7·7 mm ; P= 0·0298 ) . Onycholysis was also less in the Lamisil ® group ( P = 0·001 ) . We conclude that 12 weeks ” conlinitous oral therapy leads to higher cure rates with Lamisil ® than with itraconazole and that both drugs are equally well toler Output:	There is good evidence that a continuous regimen of terbinafine ( 250 mg/d ) for 3 months is the most effective oral treatment for fungally infected toenails .
MS21332	*TASK* the task is to summarize an input biomedical literature in six sentences *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 We tested the hypothesis that local anesthetic administered before skin incision , an example of preemptive analgesia , reduces postoperative pain for women undergoing laparoscopy , as compared with postincisional local anesthetic or placebo . Methods Patients undergoing diagnostic laparoscopy were r and omized to one of three blinded treatment groups . Treatment group A patients received local infiltration of 0.5 % bupivacaine at the surgical site before incision and a saline placebo infiltration before incision closure . Treatment group B received the saline placebo before skin incision and bupivacaine after laparoscopy but before closure of the skin incisions . For treatment group C patients , saline was infiltrated as a placebo before and after laparoscopy . All patients underwent a st and ardized general anesthetic induction and maintenance . Postoperative pain was evaluated using the modified McGill Present Pain Intensity scale . Pain and supplementary analgesic use was compared among the three treatment groups . Results A total of 57 patients completed the study for analysis . Age , weight , height , race , indication , and operating time did not vary significantly between the three groups . By 24 hours after surgery , patients in treatment group A reported significantly lower pain scores ( McGill Present Pain Intensity Scale : 0.5 ± 0.9 ) than either treatment group B ( 1.6 ± 1.3 ) or C ( 1.3 ± 1.2 ) . Group A patients also could tolerate a significantly longer time delay to their first analgesic medication than patients who received postincisional bupivacaine or than control patients who received no bupivacaine . Conclusion The preemptive administration of bupivacaine before laparoscopy results in decreased postoperative pain and should allow a more rapid return to normal activities . The popular practice of infiltrating bupivacaine at time of incision closure does not offer any benefit in the control of pain after laparoscopy Following 189 laparoscopic sterilizations with the Falope-ring , 33 cases of peroperative complications were registered . Laparotomy was required in one case . Sterilization undertaken in connection with termination of pregnancy was not associated with more peroperative complications than sterilization performed during an interval phase . In a r and omized trial comprising 100 women it was not possible to demonstrate that application of lidocaine to the tube reduced the incidence of immediate postoperative abdominal pain which occurred in 18 % of the women in the control group . A follow-up investigation of 91 women revealed change in bleeding pattern in 32 % and low abdominal pain de novo in 40 % . The frequencies of changes in bleeding pattern and of low abdominal pain were greater in women who had previously employed oral contraception than in women who had not done so . A question naire investigation comprising 169 women revealed that 38 % had developed one or more of the following symptoms : hot flushes , tendency to depression and irritability , and tachycardia . Alterations in libido were found in 26 % . 2 % regretted the sterilization . One pregnancy occurred in 172 sterilized women after an average observation period of 13 months Approximately 200 women of American Society of Anesthesiologists class I and II physical status electing outpatient laparoscopic tubal sterilization with Yoon rings were involved in a double-blind study to evaluate postoperative pain relief after intraoperative suprapubic infiltration of the fallopian mesosalpinx . The postoperative pain levels were lower after bilateral infiltration of 0.5 % bupivacaine beneath the site of ring application . Postoperative , suprapubic infiltration provided safe , prolonged and effective pain relief , allowed prompt ambulation and early discharge , and reduced the need for narcotic analgesics and postoperative analgesia Narcotic requirements in 51 day-surgery patients following laparoscopic tubal occlusion were significantly reduced ( P less than .01 ) by the use of 1 % etidocaine 5 mL , dropped on each fallopian tube from uterus to fimbrias before tubal b and ing when compared with a control group of 51 day-surgery patients who had no topical anesthetic agent . All patients received general anesthesia . Although there was no significant difference in nausea rate , the incidence of vomiting was decreased . Eight of 51 patients ( 16 % ) having topical etidocaine and 19 of 51 ( 37 % ) who had no etidocaine vomited during the postoperative period . The frequency of overnight stay was significantly reduced in the topical etidocaine group of patients ( P less than or equal to .01 ) Objective To investigate the efficacy of applying 10 ml bupivacaine 0.5%versus normal saline to the fallopian tubes under direct vision during day case laparoscopic sterilisation under general anaesthesia After laparoscopic cholecystectomy , CO2 remains within the peritoneal cavity , commonly causing pain . This prospect i ve r and omized study was performed to determine the efficacy of intraperitoneal normal saline and bupivacaine infusion on postoperative pain after laparoscopic cholecystectomy . Three hundred patients were r and omly assigned to one of six groups of 50 patients each . Group A patients served as controls . In group B patients , normal saline was infused under the right hemidiaphragm and suctioned after the pneumoperitoneum was deflated . After suction , a subhepatic closed drain was left for 24 h. In group C patients , bupivacaine 1.5 mg/kg in solution 2.5 mg/ml , minus 15 ml of this solution , which was infiltrated in the trocar wounds , was infused under the right hemidiaphragm at the end of the cholecystectomy . In group D patients , bupivacaine was given as in group C , but a subhepatic drain was left for 24 h. In group E patients , normal saline was used as in group B plus bupivacaine as in group C. Group F patients were treated as in group E , but a subhepatic drain was left for 24 h. In all groups , 15 ml of a 2.5 mg/ml bupivacaine solution was infiltrated in the trocar wounds . Postoperatively , analgesic medication usage , nausea , vomiting , and pain scores were recorded at 2 , 6 , 12 , 24 , 36 , 48 , and 72 h. Postoperative pain was reduced significantly in the patients of the treatment groups vs. the controls . Between treatment groups , patients in groups B , E , and F had the best results , while those in groups C and D had significantly greater pain than those in groups B , E , and F. It is concluded that postoperative pain after laparoscopic cholecystectomy can be significantly reduced by intraperitoneal normal saline infusion subdiaphragmatically and after its postdeflation suction , bupivacaine infusion in the same area , or without bupivacaine in case a subhepatic drainage has been needed This r and omized double-blind placebo-controlled study was design ed to evaluate the effects on postoperative pain of the local anesthetic , 0.5 % bupivacaine with epinephrine , sprayed hepatodiaphragmatically under the surgeon 's direct view during laparoscopic cholecystectomy . Metabolic endocrine responses to surgery ( glucose and cortisol ) and nonsteroidal anti-inflammatory drug requirements were investigated , as well as the presence of nausea , vomiting , and sweating . Local anesthetics or placebo solutions were given as follows . Immediately following the creation of a pneumoperitoneum , surgeons sprayed the first 20 mL of solution ( S1 ) , and an additional 20 mL of solution ( S2 ) was sprayed at the end of the operation . Patients were classified into three groups ( 14 patients per group ) . Group A received 20 mL of saline during both S1 and S2 , group B received 20 mL of saline during S1 and 20 mL of bupivacaine during S2 , and group C received 20 mL of bupivacaine during both S1 and S2 . The degree of postoperative pain was assessed using the visual analogue scale ( VAS ) and the verbal rating scale ( VRS ) on arrival in the recovery room and subsequently at time intervals of 4 h , 8 h , 12 h , and 24 h. The results of this study indicate a significant decrease of postoperative pain in patients treated with local anesthetic . VAS and VRS pain scores , as well as respiratory rate and analgesic requirements , were significantly lower in group C. The postoperative plasma cortisol level in group C was significantly lower than in groups A and We investigated , in a double-blind study , the effects of intraperitoneal local anesthetics during laparoscopic cholecystectomy . In Part A of the study 30 patients received 50 mL saline 0.9 % ( A 0 ) , bupivacaine 0.125 % ( A 125 ) , or bupivacaine 0.25 % ( A 25 ) intraperitoneally at the end of surgery . Mean maximum plasma concentrations of bupivacaine reached 0.48 mg/L ( range 0.15 - 0.90 mg/L ) in Group A 125 and 1.0 mg/L ( 0.35 - 2.10 mg/L ) in Group A 25 within 15 min ( range , 5 - 30 min ) . There was no significant difference in pain scores or opioid consumption ( patient-controlled analgesia with piritramid ) : 24 , 28 , and 13 mg/24 h among the study groups , respectively ( not significant ) . Postoperative respiratory function deteriorated in comparison to preoperative values in all study groups , but the forced vital capacity was significantly more impaired in Group A.25 . In Part B , 24 patients received placebo ( B 0 ) or bupivacaine 0.25 % ( B 25 ) . Postoperative hypoxemic periods ( oxygen saturation < 92 % ) were significantly more frequent in Group B 25 . Considering the question able benefits and the potential risks , we would not recommend the application of intraperitoneal bupivacaine during laparoscopic cholecystectomy . ( Anesth Analg 1995;81:967 - 72 OBJECTIVE To evaluate the efficacy of intraperitoneal subdiaphragmatic instillation of lidocaine and trocar site infiltration of bupivacaine to minimize postoperative pain after diagnostic microlaparoscopy performed under local anesthesia with conscious sedation . DESIGN Prospect i ve r and omized study . SETTING Day-surgery unit of Endogyn Service , Naples , and Department of Gynecologic and Pediatric Sciences , Reggio Calabria University , Catanzaro , Italy . PATIENT(S ) Sixty-one women with infertility . INTERVENTION(S ) All patients received local anesthesia and conscious sedation before surgery . After the microlaparoscopy , the treatment group was given 40 mL of intraperitoneal subdiaphragmatic 0.5 % lidocaine and 5 mL of 0.5 % bupivacaine that was infiltrated into the trocar insertion sites . The control group received no treatment . When necessary , ketoprofene or ketorolac were administered IM after surgery . MAIN OUTCOME MEASURE(S ) Postoperative pain was evaluated with the use of a visual analog scale with scores ranging from 1 - 10 immediately after surgery and over the next 48 hours . The rate at which patients were discharged from the hospital 2 hours after surgery also was recorded . RESULT ( S ) The treatment group had significantly lower pain scores both immediately after surgery and 1 , 3 , and 6 hours afterward . The need for postoperative analgesics also was significantly lower in the treatment group . The rate at which patients were discharged 2 hours after surgery was significantly higher in the treatment group . CONCLUSION ( S ) Postoperative intraperitoneal lidocaine administration and bupivacaine infiltration of the trocar sites is beneficial for patients undergoing microlaparoscopy . The effect of these drugs is temporary , but they can significantly decrease postoperative pain for approximately 6 hours and reduce the need for additional analgesics . Most important , the rate at which patients can be discharged from the hospital only 2 hours after surgery is increased significantly After laparoscopic cholecystectomy , residual gas is inevitably retained in the peritoneal cavity . An active attempt is not always made to remove it . Using a double-blind prospect i ve protocol in 40 healthy patients , we evaluated the effect of residual pneumoperitoneum on post-laparoscopic cholecystectomy pain intensity . On completion of surgery , prior to removal of the surgical instruments , the patients were r and omly divided into two groups : in the active aspiration ( AA ) group an active attempt was made to remove as much gas as possible from the peritoneal cavity , while in the nonactive aspiration ( NAA ) group no such effort was made . Postoperative pain was assessed hourly over a 4-h period with a visual analog scale ( VAS ) and a patient-controlled analgesia ( PCA ) device . During the first postoperative hour , the NAA patients made significantly ( P < 0.05 ) more dem and s ( mean ± SD ) for morphine than those in the AA group ( 31.3 ± 26.2 VS 15.3 ± 15.7 ) and also received a borderline significantly ( P = 0.056 ) larger dose ( mean ± SD ) of PCA morphine ( 3.9 ± 1.9 mg VS 2. Output:	We conclude that there was evidence for a statistically significant but clinical ly question able , important effect of intraperitoneal LA for postoperative pain control . There was evidence for a significant but short-lasting effect of mesosalpinx/fallopian tube block after sterilization , but there was a lack of evidence for any important effect of port-site infiltration . This systematic review confirms intraperitoneal and mesosalpinx local anesthetic block , not port-site infiltration , to have some impact on postoperative pain after laparoscopy
MS21333	*TASK* the task is to summarize an input biomedical literature in six sentences *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 : Investigation on anxiety , stress , depression , and quality of life ( QoL ) within STACCATO , a r and omised trial of two treatment strategies : CD4 guided scheduled treatment interruption ( STI ) compared to continuous treatment ( CT ) . Participants : Thai patients with HIV-infection enrolled in the STACCATO trial . Methods : Anxiety , depression assessed by the question naires Hospital Anxiety and Depression Scale ( HADS ) and DASS , stress assessed by the Depression Anxiety Stress Scale ( DASS ) , and QoL evaluated by the HIV Medical Outcome Study ( MOS-HIV ) question naires . Answers to question naires were evaluated at 4 time-points : baseline , 24 weeks , 48 weeks and at the end of STACCATO . Results : A total of 251 patients answered the HADS/DASS and 241 answered the MOS-HIV of the 379 Thai patients enrolled into STACCATO ( 66.2 and 63.6 % respectively ) . At baseline 16.3 % and 7.2 % of patients reported anxiety and depression using HADS scale . Using the DASS scale , 35.1 % reported mild to moderate and 9.6 % reported severe anxiety ; 8.8 % reported mild to moderate and 2.0 % reported severe depression ; 42.6 % reported mild to moderate and 4.8 % reported severe stress . We showed a significant improvement of the MHS across time ( p=0.001 ) , but no difference between arms ( p=0.17 ) . The summarized physical health status score ( PHS ) did not change during the trial ( p=0.15 ) nor between arm ( p=0.45 ) . There was no change of MHS or PHS in the STI arm , taking into account the number of STI cycle ( p=0.30 and 0.57 ) but MHS significant increased across time-points ( p=0.007 ) . Conclusion : Antiretroviral therapy improved mental health and QOL , irrespective of the treatment strategy BACKGROUND Zidovudine , the first antiretroviral agent , has short-term haematological toxicity . However , it is unclear whether patients tolerating long-term zidovudine-containing regimens will benefit from a switch to non-zidovudine-containing regimens . METHODS One hundred and fifty-eight patients enrolled in the ALIZE trial receiving zidovudine at baseline were analysed . These patients were r and omized to continue their regimen or to switch to a combination of emtricitabine , didanosine and efavirenz for 48 weeks . Changes from baseline in haemoglobin ( Hb ) , neutrophil and platelet counts were compared between arms as well as the occurrence of cardiovascular events , bacterial infections , use of haematopoietic growth factors , blood transfusion and quality of life using the Medical Outcome Study HIV ( MOS-HIV ) health survey . RESULTS Eighty-one patients continued their regimen and 77 switched . At 48 weeks , mean change from baseline in Hb were + 0.73 and -0.37 g/dL in the switch and maintenance groups , respectively ( P < 0.01 ) . Mean neutrophil counts increased by 592 and 51 cells/mm(3 ) in the switch and maintenance groups , respectively ( P = 0.02 ) . The occurrence of cardiovascular events or bacterial infections was similar in both treatment arms with no use of haematopoietic growth factors or blood transfusion . Also , mean change from baseline in MOS-HIV physical and mental health summary scores was similar in both arms . CONCLUSIONS A switch from a long-st and ing zidovudine- to a non-zidovudine-containing regimen modestly improves haematological parameters and is not associated with obvious clinical benefit Anemia , a common hematological abnormality in HIV , contributes to decreased quality of life ( QOL ) . This study assessed once-every-2-week epoetin alfa on maintaining QOL and hemoglobin ( Hb ) in anemic HIV-infected patients in a 24-week , open-label , multicenter study . HIV-infected patients ( Hb < or = 12 g/dl ) received epoetin alfa 40,000 units subcutaneously once weekly , until reaching Hb > or = 13 g/dl . Patients then entered a maintenance phase ( MP ) , in which epoetin alfa was administered every other week or at longer intervals . The trial objectives were to determine if QOL , as measured by the Medical Outcomes Study -HIV ( MOS-HIV ) general health perceptions ( GHP ) domain and Hb , was maintained . Safety was also assessed . A total of 292 patients were enrolled ( 72 % on HAART ) . Mean baseline laboratory values were Hb = 10.8 g/dl , CD4(+ ) count = 280 cells/microl , and HIV RNA = 51,867 copies/ml . In all , 81 % of patients reached Hb > or = 13 g/dl and 92 % reached Hb > or = 12 g/dl . QOL was maintained from the beginning ( GHP = 44.2 points ) to the end of MP ( GHP = 43.4 points ) with every other week or longer dosing . Mean Hb at the beginning of MP was 13.4 + /- 0.5 g/dl and was 12.8 + /- 1.4 g/dl at study end . Epoetin alfa was well tolerated ; adverse events were consistent with those reported in previous studies of epoetin alfa in HIV-infected patients . Although the clinical approach tested in this study is not consistent with current prescribing recommendations , the results confirm the efficacy of prolonged dosing intervals ( every 2 - 4 weeks ) in maintaining optimal Hb levels and QOL in anemic HIV-infected patients BACKGROUND Antiretroviral therapy including tipranavir boosted with ritonavir ( TPV/r ) has shown superior viral suppression and immunological response compared with comparator ritonavir-boosted protease inhibitor ( CPI/r ) regimens in treatment-experienced HIV-1-infected patients . This study assesses the influence of adverse events ( AEs ) on health-related quality of life ( HRQOL ) and change in HRQOL in patients treated with TPV/r versus CPI/r regimens . METHODS Changes in HRQOL over 48 weeks were assessed using Medical Outcomes Study HIV Health Survey ( MOS-HIV ) data combined from two r and omized , open-label , Phase III studies ( RESIST-1 and RESIST-2 ) . Generalized estimating equations ( GEE ) were used to compare physical health and mental health summary scores and 10 subscale scores , and to compare scores of patients with and without AEs . To compare AE incidences in the two treatment groups , AEs were exposure-adjusted . RESULTS There were 984 patients in the HRQOL analysis . AE occurrence and severity result ed in significantly lower MOS-HIV scores across both treatment arms ( P<0.05 ) . Overall incidence of AEs was higher in the CPI/r versus TPV/r group ( 562.8 versus 514.4 per 100 patient-exposure years ) ; treatment-related AEs were more frequent in the TPV/r group ( 75.0 versus 56.6 per 100 patient-exposure years ) . HRQOL was maintained in patients on TPV/r over 48 weeks of treatment across all summary and subscale scores . Compared with CPI/r , TPV/r was associated with a significant but small ( SD<0.2 ) improvement in pain scores ( + 4.8 points ; P<0.05 ) . CONCLUSIONS HRQOL was maintained across both summary and all subscale scores from baseline to 48 weeks in the TPV/r and CPI/r treatment arms , despite the incidence of treatment-related AEs Objective : To examine the effect of repeated , long-cycle structured intermittent versus continuous HAART on health-related quality of life ( HRQL ) and symptom distress in patients with chronic HIV infection and plasma HIV RNA of less than 50 copies/ml . Design : Prospect i ve survey of adult patients ( n = 46 ) enrolled in a r and omized clinical trial evaluating intermittent versus continuous HAART on immunological and virologic parameters . Patients ( n = 23 ) r and omized to structured intermittent therapy received serial cycles of 4 weeks on/8 weeks off HAART . Outcome measures : HRQL was measured by the physical and mental health summary scores of the Medical Outcomes Study HIV Health Survey ( MOS-HIV ) . Symptom distress was measured by the Symptom Distress Scale . Patients completed initial question naires prior to r and omization and at weeks 4 , 12 , and 40 of the trial via a touch screen computer in an outpatient clinic . Results : Baseline demographic and clinical characteristics were equivalent in both treatment groups . Although the mental health summary score declined significantly over time for the structured intermittent group , linear mixed modeling ANOVA indicated no significant difference across time for MOS-HIV summary and Symptom Distress Scale scores between the two treatment arms . Conclusion : In this small sample , repeated long-cycle structured intermittent therapy may not provide HRQL or symptom distress advantage compared to continuous HAART in patients with chronic HIV infection over 10 months of treatment . Further research in a heterogenous chronic HIV population and longer follow-up period is warranted Objective : To investigate the relative magnitude and duration of impact of AIDS-defining events ( ADEs ) and non-AIDS serious adverse events ( SAEs ) on health-related quality of life ( HRQoL ) among patients with advanced HIV/AIDS . Methods : We use data from OPTIMA ( OPTions In Management with Antiretrovirals ) , a multinational , r and omized , open , control , clinical management trial of treatment strategies for patients with multidrug-resistant HIV and advanced immune disease . Longitudinal models were used to determine the effects of ADEs and SAEs on HRQoL across periods before , during , and after event onset . The Medical Outcomes Study HIV Health Survey ( MOS-HIV ) physical and mental health summary scores ( MOS-PHS and MOS-MHS ) , EQ-5D , and the Health Utilities Index Mark 3 HRQoL measures were all assessed at regular follow-up intervals during the trial . Results : ADEs occurred much less frequently than SAEs ( n = 147 vs. n = 821 ) in the study sample population of 368 patients , during median follow-up of 3.96 years . Although both ADEs and SAEs had significant negative impacts on HRQoL , SAEs had at least as large an impact upon HRQoL as ADEs when both were included in a multivariate linear regression model , controlling for other covariates . However , the effect of ADEs on HRQoL was more persistent , with larger magnitude of effect across all instruments in time intervals further from the onset of the event . Conclusions : Non-AIDS SAEs occurring in patients with late-stage HIV/AIDS seem to have at least as important an immediate impact on patient HRQoL as ADEs ; however , the impact of ADEs seems to be more persistent . Our findings call for a greater emphasis on the detection and active prevention of non-AIDS SAEs in patients with late-stage HIV/AIDS This 6-month r and omized controlled trial evaluated the impact on quality of life ( QOL ) of a medication reminder device for patients with HIV . Patients were eligible if they had taken three or fewer highly active antiretroviral therapy ( HAART ) regimens or were treatment naïve . The intervention group received the Disease Management Assistance System ( DMAS ) , a prompting device that verbally reminds patients at medication times and electronically records doses , and a monthly 30 minute adherence educational session . Controls received education only . QOL was measured at baseline and 6 months using the Centers for Epidemiologic Studies Depression Scale ( CES-D ) , Instrumental Activities of Daily Living ( IADLs ) , and the Medical Outcomes Study HIV Health Survey ( MOS-HIV ) . At baseline , 62 patients completed surveys ( 31 control , 31 DMAS ) ; at month 6 , 48 patients completed surveys ( 23 control , 25 DMAS ) . At month 6 , controls had improved QOL scores for CES-D , IADLs , physical health , general health , pain , QOL , and role functioning , while participants in the DMAS arm had some deterioration in QOL scores . These differences persisted after controlling for demographics , baseline CD4 , and adherence . DMAS was associated with improved adherence but decreased QOL OBJECTIVES Treatment advances have transformed human immunodeficiency virus/acquired immune deficiency syndrome ( HIV/AIDS ) into a chronic manageable disease ; quality of life ( QoL ) has become an important health outcome . Some studies have shown the individual effects of acupuncture and the relaxation response ( RR ) in improving QoL of patients with HIV/AIDS . In light of the presumed shared features of acupuncture and the RR , we conducted a pilot study to examine the effects of adding the RR to usual acupuncture treatment on improving the QoL of HIV/AIDS patients . DESIGN Two-arm double-blind r and omized controlled trial . SETTING S/LOCATION AND SUBJECTS : We enrolled 119 patients with HIV/AIDS ( mean age 46 years , 85 % male ) who had at least 1 of the highly prevalent HIV-related symptoms and who were receiving acupuncture treatment in an acup Output:	Conclusions A systematic review of PRO study results showed both the MOS-HIV and EQ-5D were responsive to changes between groups and /or over time in treatment-naïve HIV-infected patients . These instruments may be used either individually or together in clinical trials to measure changes in HRQL
MS21334	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: There is indirect evidence for a gender difference in nitric oxide ( NO ) synthesis from vascular endothelium . The aim of the present study was to determine NO production more directly in healthy women and men by the measurement of 15N nitrate excreted in urine after the intravenous administration of L-[15N]2-guanidino arginine . Twenty-four healthy volunteers ( 13 men aged 22 to 40 years and 11 women aged 23 to 42 years ) participated in this study . No subjects were receiving any medication . Women were studied between the 7th and 14th days of their menstrual cycles . Arterial blood pressure was measured oscillometrically , and 1.13 micromol L-[15N]2 arginine was administered intravenously after an overnight fast . Urine was collected for the next 36 hours in separate 12-hour periods . Urinary 15N/14N nitrate ratio was assessed by dry combustion in an isotope ratio mass spectrometer . Mean 36-hour urinary 15N nitrate excretion was greater in women than in men ( 2111+/-139 versus 1682+/-87 etamol ; P<0.05 ) . Furthermore , total urinary 15N nitrate excretion was associated inversely with the mean arterial blood pressure in the whole group of subjects ( coefficient of correlation , 0.47 ; P=0.022 ) . The present data show that whole-body production of NO is greater in healthy premenopausal women than in men under ambulatory conditions . The cellular origin of NO measured in this study is unknown , but differences in endothelial production could underlie differences in vascular function between men and women & NA ; Current methods for assessing vasomotor endothelial function are impractical for use in large studies . We tested the hypothesis that pulse‐wave analysis ( PWA ) combined with provocative pharmacological testing might provide an alternative method . Radial artery waveforms were recorded and augmentation index ( AIx ) was calculated from derived aortic waveforms . Thirteen subjects received sublingual nitroglycerin ( NTG ) , inhaled albuterol , or placebo . Twelve subjects received NTG , albuterol , and placebo separately during an infusion of NG‐monomethyl‐L‐arginine ( LNMMA ) or norepinephrine . Twenty‐seven hypercholesterolemic subjects and 27 controls received NTG followed by albuterol . Endothelial function was assessed by PWA and forearm blood flow in 27 subjects . Albuterol and NTG both significantly and repeatably reduced AIx ( P<0.001 ) . Only the response to albuterol was inhibited by LNMMA ( −9.8±5.5 % vs −4.7±2.7 % ; P=0.02 ) . Baseline AIx was higher in the hypercholesterolemic subjects , who exhibited a reduced response to albuterol ( P=0.02 ) but not to NTG when compared with matched controls . The responses to albuterol and acetylcholine were correlated ( r=0.5 , P= 0.02 ) . Consistent with an endothelium‐dependent effect , the response to albuterol was substantially inhibited by LNMMA . Importantly , the response to albuterol was reduced in subjects with hypercholesterolemia and was correlated to that of intra‐arterial acetylcholine . This methodology provides a simple , repeatable , noninvasive means of assessing endothelial function in vivo We investigated the effects of a high dietary supplement of arginine on plasma arginine , ornithine , and leucine kinetics and on urea production and excretion in five healthy young adult men . Subjects received either 56 or 561 mg arginine.kg-1.day-1 for 6 days via a complete L-amino acid diet , and on day 7 a tracer protocol ( first 3 h fasted ; next 5 h fed ) was conducted , involving primed constant intragastric infusions of L-[15N2-guanidino,5,5 - 2H2]arginine , L-[5 - 13C]ornithine , L-[5,5,5 - 2H3]leucine , and [15N2]urea , with a prime of H13CO3 . Plasma arginine and ornithine fluxes increased significantly ( P < 0.05 ) with arginine supplementation , as did the rate of conversion of plasma labeled arginine to ornithine ( P < 0.05 ) and rate of ornithine oxidation ( P < 0.001 ) . However , absolute changes in ornithine kinetics were less than those for arginine or those based on changes expected from the change in arginine intake , implying a complex compartmentation in both whole body arginine and ornithine metabolism . The plasma NO3 concentration , daily output of total NO3 , and conversion of [15N]arginine to NO3 did not differ between the diets . Urea production and excretion were reduced significantly with arginine supplementation , suggesting an anabolic effect on the whole body nitrogen economy , possibly via the raised plasma insulin levels ( P = 0.013 ) during the pr and ial phase OBJECTIVE A reduced bioactivity of endothelial nitric oxide ( NO ) has been implicated in the pathogenesis of atherosclerosis . In humans , the endothelial L-arginine-NO pathway has been indirectly assessed via the flow response to endothelium-dependent vasodilators locally administered into the coronary , pulmonary or forearm circulation . However , biochemical quantification of endothelial NO formation in these organ circulations has been hampered so far because of the rapid metabolism of NO . Therefore , we aim ed to work out a reliable biochemical index to assess endothelial NO formation in human circulation . METHODS In 33 healthy volunteers , forearm blood flow ( FBF ) was measured by st and ard techniques of venous occlusion plethysmography at rest , after local application of the endothelium-dependent vasodilator acetylcholine ( ACH ) , the endothelium-independent vasodilator papaverine ( PAP ) , the stereospecific inhibitor of endothelial NO synthase ( eNOS ) L-NMMA , and L-arginine ( ARG ) , the natural substrate of eNOS . In parallel , nitrite and nitrate concentrations in blood sample s taken from the antecubital vein were measured by HPLC using anion-exchange chromatography in combination with electrochemical and ultraviolet detection following a specific sample preparation method . RESULTS ACH dose-dependently increased resting FBF ( from 3.0 + /- 0.3 to 10.4 + /- 0.9 ml/min per 100 ml tissue ) and serum nitrite concentration ( from 402 + /- 59 to 977 + /- 82 nmol/l , both p < 0.05 , n = 12 ) . A significant correlation was observed between the changes in FBF and the serum nitrite concentration ( r = 0.61 , p < 0.0001 ) . L-NMMA reduced resting FBF and endothelium-dependent vasodilation by 30 % and this was paralleled by a significant reduction in serum nitrite concentration at the highest dose of ACH ( n = 9 , p < 0.001 ) . PAP increased FBF more than fourfold , but did not affect serum nitrite concentration ( n = 11 ) , whereas ARG significantly increased both FBF and nitrite . Basal serum nitrate amounted to 25 + /- 4 mumol/l and remained constant during the application of ACH , PAP and L-NMMA . CONCLUSIONS The concentration of serum nitrite sensitively reflects changes in endothelial NO formation in human forearm circulation . This biochemical measure may help to characterize the L-arginine-NO pathway in disease states associated with endothelial dysfunction and to further eluci date its pathophysiological significance for the development of atherosclerosis in humans In humans , the role of nitric oxide ( NO ) in host defence is controversial . We prospect ively studied plasma levels of nitrate , the stable end-product of NO formation , during acute infection in 43 patients controlled with regard to dietary nitrate/nitrite . During acute gastroenteritis the mean plasma nitrate level was significantly increased compared with at recovery 4 - 5 weeks later ( 118 vs. 32.5 micromol/l ; p < 0.001 ) , in contrast with the findings in patients with acute pneumonia ( PN ; 34.6 vs. 42.8 micromol/l ) or febrile urinary tract infection ( UTI ; 27.7 vs. 31.3 micromol/l ) . In a second group of 20 retrospectively studied patients with severe PN or UTI , of whom 70 % were bacteraemic , no significantly increased nitrate levels could be demonstrated during the acute stage of infection . These findings indicate that increased NO production , as measured by plasma nitrate , is not a general finding in patients with acute infectious diseases , but may rather be associated with certain pathogens or sites of infection Output:	Three protocol s were identified , including the arginine-citrulline , the arginine-nitrate , and the oxygen-nitrate protocol s. The arginine-citrulline protocol showed a wider variability compared to the arginine-nitrate and oxygen-nitrate protocol s. The direction of the association between disease state and rate of NO production was essentially determined by the etiopathogenesis of the disorder ( inflammatory , metabolic , vascular ) . The precision of several aspects of the techniques and the validity of some assumptions made remain unknown , and there is a paucity of information about physiological rates of NO production from childhood over adolescence to old age
MS21335	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Significance MicroRNAs ( miRNAs ) are small ∼22-nt RNAs that are important regulators of posttranscriptional gene expression . Since their initial discovery , they have been shown to be involved in many cellular processes , and their misexpression is associated with disease etiology . Currently , nearly 2,800 human miRNAs are annotated in public repositories . A key question in miRNA research is how many miRNAs are harbored by the human genome . To answer this question , we examined 1,323 short RNA sequence sample s and identified 3,707 novel miRNAs , many of which are human-specific and tissue-specific . Our findings suggest that the human genome expresses a greater number of miRNAs than has previously been appreciated and that many more miRNA molecules may play key roles in disease etiology . Two decades after the discovery of the first animal microRNA ( miRNA ) , the number of miRNAs in animal genomes remains a vexing question . Here , we report findings from analyzing 1,323 short RNA sequencing sample s ( RNA-seq ) from 13 different human tissue types . Using stringent thresholding criteria , we identified 3,707 statistically significant novel mature miRNAs at a false discovery rate of ≤0.05 arising from 3,494 novel precursors ; 91.5 % of these novel miRNAs were identified independently in 10 or more of the processed sample s. Analysis of these novel miRNAs revealed tissue-specific dependencies and a commensurate low Jaccard similarity index in intertissue comparisons . Of these novel miRNAs , 1,657 ( 45 % ) were identified in 43 data sets that were generated by cross-linking followed by Argonaute immunoprecipitation and sequencing ( Ago CLIP-seq ) and represented 3 of the 13 tissues , indicating that these miRNAs are active in the RNA interference pathway . Moreover , experimental investigation through stem-loop PCR of a r and om collection of newly discovered miRNAs in 12 cell lines representing 5 tissues confirmed their presence and tissue dependence . Among the newly identified miRNAs are many novel miRNA clusters , new members of known miRNA clusters , previously unreported products from uncharacterized arms of miRNA precursors , and previously unrecognized paralogues of functionally important miRNA families ( e.g. , miR-15/107 ) . Examination of the sequence conservation across vertebrate and invertebrate organisms showed 56.7 % of the newly discovered miRNAs to be human-specific whereas the majority ( 94.4 % ) are primate lineage-specific . Our findings suggest that the repertoire of human miRNAs is far more extensive than currently represented by public repositories and that there is a significant number of lineage- and /or tissue-specific miRNAs that are uncharacterized Neurofibrillary tangles ( NFT ) constitute one of the cardinal histopathological features of Alzheimer 's disease ( AD ) . To explore in vivo molecular processes involved in the development of NFTs , we compared gene expression profiles of NFT-bearing entorhinal cortex neurons from 19 AD patients , adjacent non-NFT-bearing entorhinal cortex neurons from the same patients , and non-NFT-bearing entorhinal cortex neurons from 14 non-demented , histopathologically normal controls ( ND ) . Of the differentially expressed genes , 225 showed progressively increased expression ( AD NFT neurons > AD non-NFT neurons > ND non-NFT neurons ) or progressively decreased expression ( AD NFT neurons < AD non-NFT neurons < ND non-NFT neurons ) , raising the possibility that they may be related to the early stages of NFT formation . Immunohistochemical studies confirmed that many of the implicated proteins are dysregulated and preferentially localized to NFTs , including apolipoprotein J , interleukin-1 receptor-associated kinase 1 , tissue inhibitor of metalloproteinase 3 , and casein kinase 2 , beta . Functional validation studies are underway to determine which c and i date genes may be causally related to NFT neuropathology , thus providing therapeutic targets for the treatment of AD Since 1992 , the amyloid cascade hypothesis has played the prominent role in explaining the etiology and pathogenesis of Alzheimer 's disease ( AD ) . It proposes that the deposition of β-amyloid ( Aβ ) is the initial pathological event in AD leading to the formation of senile plaques ( SPs ) and then to neurofibrillary tangles ( NFTs ) , neuronal cell death , and ultimately dementia . While there is substantial evidence supporting the hypothesis , there are also limitations : ( 1 ) SP and NFT may develop independently , and ( 2 ) SPs and NFTs may be the products rather than the causes of neurodegeneration in AD . In addition , r and omized clinical trials that tested drugs or antibodies targeting components of the amyloid pathway have been inconclusive . This paper provides a critical overview of the evidence for and against the amyloid cascade hypothesis in AD and provides suggestions for future directions There has been a plausible link between human exposure to aluminum and Alzheimer 's disease for several decades . We contend that the only direct and ethically acceptable experimental test of the ' aluminum hypothesis ' , which would provide unequivocal data specific to the link , is to test the null hypothesis that a reduction in the body burden of aluminum to its lowest practical limit would have no influence upon the incidence , progression , or severity of Alzheimer 's disease . Herein we are testing the hypothesis that silicon-rich mineral waters can be used as non-invasive methods to reduce the body burden of aluminum in individuals with Alzheimer 's disease and a control group consisting of their carers and partners . We have shown that drinking up to 1 L of a silicon-rich mineral water each day for 12 weeks facilitated the removal of aluminum via the urine in both patient and control groups without any concomitant affect upon the urinary excretion of the essential metals , iron and copper . We have provided preliminary evidence that over 12 weeks of silicon-rich mineral water therapy the body burden of aluminum fell in individuals with Alzheimer 's disease and , concomitantly , cognitive performance showed clinical ly relevant improvements in at least 3 out of 15 individuals . This is a first step in a much needed rigorous test of the ' aluminum hypothesis of Alzheimer 's disease ' and a longer term study involving many more individuals is now warranted The formation of 5-hydroxymethylcytosine ( 5hmC ) , a key intermediate of DNA demethylation , is driven by the ten eleven translocation ( TET ) family of proteins that oxidize 5-methylcytosine ( 5mC ) to 5hmC. To determine whether methylation/demethylation status is altered during the progression of Alzheimer 's disease ( AD ) , levels of TET1 , 5mC and subsequent intermediates , including 5hmC , 5-formylcytosine ( 5fC ) and 5-carboxylcytosine ( 5caC ) were quantified in nuclear DNA from the hippocampus/parahippocampal gyrus ( HPG ) and the cerebellum of 5 age-matched normal controls , 5 subjects with pre clinical AD ( PCAD ) and 7 late-stage AD ( LAD ) subjects by immunochemistry . The results showed significantly ( p < 0.05 ) increased levels of TET1 , 5mC , and 5hmC in the HPG of PCAD and LAD subjects . In contrast , levels of 5fC and 5caC were significantly ( p < 0.05 ) decreased in the HPG of PCAD and LAD subjects . Overall , the data suggest altered methylation/demethylation patterns in vulnerable brain regions prior to the onset of clinical symptoms in AD suggesting a role in the pathogenesis of the disease BACKGROUND Memory declines more rapidly with age in apolipoprotein E ( APOE ) epsilon4 carriers than in APOE epsilon4 noncarriers , and APOE epsilon4 homozygotes ' cognitive performances correlate with stressors . These changes could represent presymptomatic disease in some , despite their youth . OBJECTIVE To show that presymptomatic APOE epsilon4 homozygotes experience greater psychometric decline at a younger age than APOE epsilon4 heterozygotes and noncarriers before the diagnosis of mild cognitive impairment ( MCI ) and Alzheimer disease ( AD ) . DESIGN Prospect i ve observational study SETTING Academic medical center . PARTICIPANTS A total of 43 APOE epsilon4 homozygotes , 59 APOE epsilon4 heterozygotes , and 112 APOE epsilon4 noncarriers aged 50 to 69 years were cognitively healthy and matched at entry according to age , educational level , and sex . INTERVENTION Neuropsychological battery given every 2 years . MAIN OUTCOME MEASURES Predefined test and cognitive domain decline criteria applied to consecutive epochs . RESULTS Of 214 participants , 48 showed no decline on any test , 126 showed decline on only 1 test in 1 or more domains , and 40 showed decline on 2 or more tests in 1 or more domains . Cognitive domain decline occurred in 4 of 10 APOE epsilon4 homozygotes 60 years and older at entry ( 40.0 % ) compared with 5 of 66 APOE epsilon4 heterozygotes and noncarriers ( 7.6 % ) ( P = .02 ) and was more predictive of subsequent decline than nondomain decline ( 17 of 24 [ 70.8 % ] vs 29 of 70 [ 41.4 % ] ; P = .01 ) . Decline on any memory test was predictive of further decline ( P < .001 ) , as was memory domain decline ( P = .006 ) in all genetic subgroups . Seven participants developed MCI ( in 6 ) or AD ( in 1 ) , of whom 5 were APOE epsilon4 homozygotes ( P = .008 ) . Retrospective comparison showed that those who experienced multidomain , memory , and language domain decline had lower spatial and memory scores at entry than those who experienced no decline . CONCLUSIONS APOE epsilon4 homozygotes in their 60s have higher rates of cognitive domain decline than APOE epsilon4 heterozygotes or noncarriers before the diagnosis of MCI and AD , thus confirming and characterizing the existence of a pre-MCI state in this genetic subset We present here both linear regressions and multivariate analyses correlating three global neuropsychological tests with a number of structural and neurochemical measurements performed on a prospect i ve series of 15 patients with Alzheimer 's disease and 9 neuropathologically normal subjects . The statistical data show only weak correlations between psychometric indices and plaques and tangles , but the density of neocortical synapses measured by a new immunocytochemical/densitometric technique reveals very powerful correlations with all three psychological assays . Multivariate analysis by stepwise regression produced a model including midfrontal and inferior parietal synapse density , plus inferior parietal plaque counts with a correlation coefficient of 0.96 for Mattis 's Dementia Rating Scale . Plaque density contributed only 26 % of that strength Positional cloning studies to identify disease genes are being carried out for many human genetic diseases . Such studies often include a genome-scan linkage analysis to identify the rough chromosomal location of a disease gene , fine structure genetic mapping to define and narrow the chromosomal interval in which the disease gene may be located , and physical mapping and gene identification in the genetically defined interval to clone the disease gene . During the planning of a positional cloning study , it is important to know that , if linkage is found , the genetic interval identified is likely to be sufficiently narrow to be dissected efficiently by methods of physical mapping and gene identification . Thus , we wish to know the limits of resolution of a genetic linkage study . In this paper , I determine for Mendelian diseases the distributions and moments of three measures of linkage resolution : ( 1 ) in a set of N chromosomes , the distance between the nearest crossovers that flank a disease locus , ( 2 ) the distance between the nearest genetic markers that flank the pair of flanking crossovers after a genome scan , and ( 3 ) the distance between the nearest flanking markers after additional r and omly placed markers are generated and typed in an identified interval . These results provide explicit sample -size guidelines for future positional cloning studies of Mendelian diseases and make possible a more objective evaluation of whether a proposed positional cloning study is likely to be successful . I also briefly discuss the more difficult problem of linkage resolution for complex genetic diseases BACKGROUND Imaging with amyloid-β PET can potentially aid the early and accurate diagnosis of Alzheimer 's disease . Florbetaben ( ¹⁸F ) is a promising ¹⁸F-labelled amyloid-β-targeted PET tracer in clinical development . We aim ed to assess the sensitivity and specificity of florbetaben ( ¹⁸F ) PET in discriminating between patients with probable Alzheimer 's disease and elderly healthy controls . METHODS We did a multicentre , open-label , non-r and omised phase 2 study in 18 centres in Australia , Germany , Switzerl and , and the USA . Imaging with florbetaben ( ¹⁸F ) PET was done on patients with probable Alzheimer 's disease ( age 55 years or older , mini-mental state examination [ MMSE ] score=18 - 26 , clinical dementia rating [CDR]=0·5 - 2·0 ) and age-matched healthy controls ( MMSE ≥ 28 , CDR=0 ) . Our primary objective was to establish the diagnostic efficacy of the scans in differentiating between patients with probable disease and age-matched health Output:	The promising newer approaches may provide reliable means of early and more specific diagnosis and help identify therapeutic interventions for LOAD
MS21336	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Recognizing the need to offer alternative methods of brief interventions , this study developed correspondence treatments for low-dependent problem drinkers and evaluated their impact . One hundred and twenty-one problem drinkers were recruited by media advertisements and were r and omly allocated to a full cognitive-behavioural treatment programme ( CBT ) or to a minimal intervention condition ( MI ) that gave information regarding alcohol misuse and instructions to record drinking++ . As predicted , CBT was more effective than MI in reducing alcohol consumption over the 4-month controlled trial period . CBT produced a 50 % fall in consumption , bringing the average intake of subjects within recommended maximum levels . Treatment gains at 6 months were well maintained to 12 months . High levels of consumer satisfaction , a high representation of women and a substantial participation from isolated rural areas attested to the feasibility of the correspondence programme as an alternative treatment . However , some drinking occasions still involved high intake for a significant subgroup of subjects , and this issue will be addressed in future programmes . The results supported the use of correspondence delivery as a means of promoting early engagement and equity of access between city and country areas Alcoholics from two hospital-based treatment centers participated in an experimental test of the effects of extended aftercare on inpatient recovery rates . At discharge from inpatient treatment , subjects were r and omly assigned either to an experimental group scheduled to be called by a center counselor every 2 weeks for 1 year or to a control group that experienced only the usual treatment . Follow-up interviews conducted approximately 12 months after hospital discharge found that the experimental group had no higher recovery rates than the control group . There was weak evidence that the calls reduced the burden that alcoholics place on community control and service agencies . There was no evidence that either the phone calls were more effective for some patients than for others or that some kinds of phone calls were more effective than others . Although most subjects said they liked the calls , wanted them to continue and perceived them as " good treatment , " only one subject gave the calls credit for helping him maintain sobriety The mortality experience of convicted drinking drivers ( second offenders ) ( N = 347 ) r and omly assigned to rehabilitation and control groups in two Ontario cities was examined . Over a follow-up period ranging between 8 and 13 years , 14 ( 11.0 % ) of the controls and 17 ( 7.7 % ) of the rehabilitation group died . Direct comparisons of the r and omly assigned control and treatment groups revealed a tendency for lower total mortality and significantly lower mortality from accidental and violent death in those assigned to rehabilitation . Additional comparisons involving a combined rehabilitation group ( N = 487 ) ( rehabilitation participants r and omly and not r and omly assigned ) confirmed these observations BACKGROUND Employee-assistance programs sponsored by companies or labor unions identify workers who abuse alcohol and refer them for care , often to inpatient rehabilitation programs . Yet the effectiveness of inpatient treatment , as compared with a variety of less intensive alternatives , has repeatedly been called into question . In this study , anchored in the work site , we compared the effectiveness of m and atory in-hospital treatment with that of required attendance at the meetings of a self-help group and a choice of treatment options . METHODS We r and omly assigned a series of 227 workers newly identified as abusing alcohol to one of three rehabilitation regimens : compulsory inpatient treatment , compulsory attendance at Alcoholics Anonymous ( AA ) meetings , and a choice of options . Inpatient backup was provided if needed . The groups were compared in terms of 12 job-performance variables and 12 measures of drinking and drug use during a two-year follow-up period . RESULTS All three groups improved , and no significant differences were found among the groups in job-related outcome variables . On seven measures of drinking and drug use , however , we found significant differences at several follow-up assessment s. The hospital group fared best and that assigned to AA the least well ; those allowed to choose a program had intermediate outcomes . Additional inpatient treatment was required significantly more often ( P less than 0.0001 ) by the AA group ( 63 percent ) and the choice group ( 38 percent ) than by subjects assigned to initial treatment in the hospital ( 23 percent ) . The differences among the groups were especially pronounced for workers who had used cocaine within six months before study entry . The estimated costs of inpatient treatment for the AA and choice groups averaged only 10 percent less than the costs for the hospital group because of their higher rates of additional treatment . CONCLUSIONS Even for employed problem drinkers who are not abusing drugs and who have no serious medical problems , an initial referral to AA alone or a choice of programs , although less costly than inpatient care , involves more risk than compulsory inpatient treatment and should be accompanied by close monitoring for signs of incipient relapse The ' Pressures to Change ' approach to working with the partners of drinkers is a structured procedure for promoting change in resistant drinkers . In this study 22 women and one man were r and omly allocated to two treatment conditions and one no-treatment waiting list control condition in an experimental evaluation of the procedure . Group 1 was treated individually and Group 2 was treated as a group . Almost two-thirds of the drinking partners of clients in treatment made a significant move towards change , compared with none of the drinkers in the waiting list control condition Patients ( N = 114 ) consecutively entering a medical service with ulcer , cirrhosis or pancreatitis , currently drinking and not currently active in alcoholism treatment were r and omly assigned to motivational intervention ( MI ) or to a control group . Increased utilization of alcoholism programs and self-reported sobriety at 10 weeks were assessed . MI consisted of three separate discussion s of the relationship of the patient 's disease to continued drinking and the compassionate offer of treatment . Two persons skilled in treatment also met with each MI subject and discussed treatment possibilities for them , facilitating entrance if desired . Patients in both the MI and control group were treated for their medical condition by a medical team and alcoholism treatment was always recommended . Outcome was evaluated for the period from the 10th to the 16th week after return to the community by interview of patient and household contacts and by the keeping of appointments . There were no differences between the control and MI groups , with at least 38 % remaining sober for the 10-week interval ; the study size was sufficient to detect reliably a 30 % improvement . We conclude that additional motivational intervention to this level was not beneficial to the hospitalized alcoholic with disease . There was a statistically significant increase in sobriety among patients who either undertook alcoholism therapy , accepted all parts of the study or kept clinical appointments 151 problem drinkers ( 105 men and 46 women ) were recruited from the general medical and psychiatric services of a district general hospital and were allocated r and omly to a community-based day centre ( ACCEPT ) or st and ard hospital inpatient and outpatient services . 115 patients ( 79 % ) were followed up at 12 months . The group as a whole showed improvement in all outcome indices at the 3-month follow-up , and this was maintained at 6 and 12 months . Patients assigned to ACCEPT services cl aim ed to have reduced their alcohol intake ( 55 % ) more than their hospital counterparts ( 37 % ) , and this was confirmed by their informants . Patients referred from the psychiatric services reduced their alcohol intake more than those from general medical services . It is concluded that treatment at a community day centre is at least as cost effective as hospital treatment of alcohol abuse The objective of the study was to determine the effectiveness of advice from general practitioners to heavy drinking men ( consuming 350 - 1050 grams of alcohol per week ) to reduce their alcohol consumption . One hundred and fifty-four men recruited from eight general practice s were allocated r and omly to treatment and control groups . Men in the treatment group received advice from their own general practitioner . At one year follow-up , when analyzed according to intention to treat , the treatment group had reduced their consumption by an excess of 65 grams of alcohol per week when compared with the control group ( p less than 0.05 ) . General practitioners should be recommended to screen for alcohol consumption amongst their patients and to give advice to those found to be at risk because of their drinking The importance of previous suicidal behavior for the treatment of alcoholics was analyzed in a long-term outpatient treatment study . In a series of 72 patients , 21 patients , ( 29 % ) , 17 men and 4 women , had previously made at least one suicide attempt or had seriously threatened to kill themselves ( 3 cases ) . In comparison with the other alcoholics , those with previous suicidal behavior had a similar attrition rate , they were not more troublesome in treatment , and they had the same rate of favorable outcome during the third year after start of treatment . They differed from the other alcoholics in having a more severe abuse and a less favorable outcome during the initial part of the treatment . In conclusion , our results support the possibility of a long-term outpatient treatment strategy in alcoholics with previous suicide attempts To date , the published controlled trials on exposure to alcohol cues have had an abstinence treatment goal . A modification of cue exposure ( CE ) for moderation drinking , which incorporated priming doses of alcohol , could train participants to stop drinking after 2 to 3 drinks . This study examined the effects of modified CE within sessions , combined with directed homework practice . Nondependent problem drinkers who requested a moderation drinking goal were r and omly allocated to modified CE or st and ard cognitive-behavior therapy ( CBT ) for alcohol abuse . Both interventions were delivered in 6 90-min group sessions . Eighty-one percent of eligible participants completed treatment and follow-up assessment . Over 6 months , CE produced significantly greater reductions than CBT in participants ' reports of drinking frequency and consumption on each occasion . No pretreatment variables significantly predicted outcome . The modified CE procedure appears viable for nondependent drinkers who want to adopt a moderate drinking goal Output:	Interventions among convicted drunk drivers reduced motor vehicle crashes and injuries . The results suggest that treatment for problem drinking may reduce injuries and their antecedents .
MS21337	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: HYPOTHESIS Laparoscopic anterior 90 degrees partial fundoplication for gastroesophageal reflux is associated with a lower incidence of postoperative dysphagia and other adverse effects compared with laparoscopic Nissen fundoplication . DESIGN A multicenter , prospect i ve , double-blind , r and omized controlled trial . SETTING Nine university teaching hospitals in 6 major cities in Australia and New Zeal and . PARTICIPANTS One hundred twelve patients with proven gastroesophageal reflux disease presenting for laparoscopic fundoplication were r and omized to undergo either a Nissen ( 52 patients ) or an anterior 90 degrees partial procedure ( 60 patients ) . Patients with esophageal motility disorders , patients requiring a concurrent abdominal procedure , and patients who had undergone previous antireflux surgery were excluded from this study . INTERVENTIONS Laparoscopic Nissen fundoplication with division of the short gastric vessels or laparoscopic anterior 90 degrees partial fundoplication . MAIN OUTCOME MEASURES Independent assessment of dysphagia , heartburn , and overall satisfaction 1 , 3 , and 6 months after surgery using multiple clinical grading systems . Objective measurement of esophageal manometric parameters , esophageal acid exposure , and endoscopic assessment . RESULTS Postoperative dysphagia , and wind-related adverse effects were less common after a laparoscopic anterior 90 degrees partial fundoplication . Relief of heartburn was better following laparoscopic Nissen fundoplication . Overall satisfaction was better after anterior 90 degrees partial fundoplication . Lower esophageal sphincter pressure , acid exposure , and endoscopy findings were similar for both procedures . CONCLUSIONS At the 6-month follow-up , laparoscopic anterior 90 degrees culine partial fundoplication is followed by fewer adverse effects than laparoscopic Nissen fundoplication with full fundal mobilization , and it achieves a higher rate of satisfaction with the overall outcome . However , this is offset to some extent by a greater likelihood of recurrent gastroesophageal reflux symptoms BACKGROUND Total fundoplication for gastro-oesophageal reflux disease may be followed by unwanted side-effects . A r and omized trial demonstrated that an anterior 180 degrees partial fundoplication achieved effective reflux control and was associated with fewer side-effects in the short term than total fundoplication . This paper reports longer-term ( 5 year ) outcomes from that trial . METHODS Between December 1995 and June 1997 , 107 patients were r and omized to undergo either laparoscopic total fundoplication or a laparoscopic anterior 180 degrees fundoplication . After 5 years , 101 of 103 eligible patients ( 51 total , 50 anterior ) were available for follow-up . Each patient was interviewed by a single blinded investigator and a st and ardized question naire was completed . The question naire focused on symptoms and overall satisfaction with the results of fundoplication . RESULTS There were no significant differences between the two groups with regard to control of heartburn or patient satisfaction with the overall outcome . Dysphagia , measured by a visual analogue score for solid food and a composite dysphagia score , was worse at 5 years after total fundoplication . Symptoms of bloating , inability to belch and flatulence were also more common after total fundoplication . Reoperation was required for dysphagia in three patients after total fundoplication and for recurrent reflux in three patients after anterior fundoplication . CONCLUSION Anterior 180 degrees partial fundoplication was as effective as total fundoplication for managing the symptoms of gastro-oesophageal reflux in the longer term . It was associated with a lower incidence of side-effects , although this was offset by a slightly higher risk of recurrent reflux symptoms In Barrett ’s esophagus , total abolition of reflux may give maximum protection against the development of malignancy . To determine whether laparoscopic anterior fundoplication gives the same degree of antireflux control as a total fundoplication , we analyzed a prospect ively followed cohort of patients from r and omized controlled trials of laparoscopic antireflux surgery . There were 167 patients who returned for routine esophageal pH studies within 6 months of surgery ( 123 laparoscopic total fundoplications and 44 anterior fundoplications ) . There was no difference in percentage time pH < 4 between fundoplication groups , but the total number of reflux episodes was significantly different ( total fundoplication , four reflux events vs. partial fundoplication , six reflux events ; p = 0.03 ) . It is difficult to believe that this difference is either biologically or clinical ly important . In patients with a second esophageal pH study more than 5 years later , both the percentage time pH < 4 ( 0.1 % total fundoplication vs. 2.7 % partial fundoplication ; p = 0.004 ) and total number of reflux episodes ( three total fundoplication vs. 24 partial fundoplication ; p = 0.002 ) were significantly different . However , the postoperative esophageal acid exposure was within the normal range for both total and partial fundoplication , so whether the statistical difference is clinical ly important , remains a moot point Objective : To compare 10 years outcome of a multicenter r and omized controlled trial on laparoscopic ( LNF ) and conventional Nissen fundoplication ( CNF ) , with focus on effectiveness and reoperation rate . Summary of Background Data : LNF has replaced CNF as surgical treatment for gastroesophageal reflux disease ( GERD ) . Decisions are based on equal short-term effectiveness and reduced morbidity , but confirmation by long-term level 1 evidence is lacking . Methods : From 1997 to 1999 , 177 proton pump inhibitor (PPI)-refractory GERD patients were r and omized to undergo LNF or CNF . The 10 years results of surgery on reflux symptoms , general health , PPI use , and reoperation rates , are described . High-resolution manometry , 24-hour pH-impedance monitoring and barium swallow were performed in symptomatic patients only . Results : A total of 148 patients ( 79 LNF , 69 CNF ) participated in this 10-year follow-up study . GERD symptoms were relieved in 92.4 % and 90.7 % ( NS ) after LNF and CNF , respectively . Severity of heartburn and dysphagia were similar , but slightly more patients had relief of regurgitation after LNF ( 98.7 % vs. 91.0 % ; P = 0.030 ) . The percentage of patients using PPIs slowly increased with time in both groups to 26.6 % for LNF and 22.4 % for CNF ( NS ) . General health ( 74.7 % vs. 72.7 % ; NS ) and quality of life ( visual analogue scale score : 65.3 vs. 61.4 ; NS ) improved similarly in both groups . The percentage of patients who would have opted for surgery again was similar as well ( 78.5 % vs. 72.7 % ; NS ) . Twice as many patients underwent reoperation after CNF compared with LNF ( 12 [ 15.2 % ] vs. 24 [ 34.8 % ] ; P = 0.006 ) , including a higher number of incisional hernia corrections ( 2 vs. 9 ; P = 0.015 ) . Mean interval between operation and reintervention was longer after CNF ( 22.9 vs. 50.6 months ; P = 0.047 ) . Of the patients who were dependent on daily PPI therapy at 10 years ( LNF 10 , CNF 10 ) , 7 patients ( LNF 3 , CNF 4 ) had recurrent GERD on pH-impedance monitoring , 5 of them with some form of anatomic recurrence . A total of 13 of 20 ( 65.0 % ) patients did not have recurrent GERD . Fourteen patients had an abnormal high-resolution manometry . Conclusions : CNF carries a higher risk for surgical reintervention compared with LNF , mainly due to incisional hernia corrections . The 10-year effectiveness of LNF and CNF is comparable in terms of improvement of GERD symptoms , PPI use , quality of life , and objective reflux control . Consequently , the long-term results from this trial lend level 1 support to the use of LNF as the surgical procedure of choice for GERD BACKGROUND The effect of total ( Nissen ) and anterior partial fundoplication ( APF ) for the surgical treatment of gastroesophageal reflux disease ( GERD ) on the motor behavior of the esophagogastric axis has not been fully assessed . The purpose of this study was to assess any alterations in lower esophageal sphincter ( LES ) and gastric fundus motor parameters in GERD patients after Nissen or APF fundoplication . METHODS Twenty four patients with documented GERD underwent either laparoscopic Nissen fundoplication ( n = 12 ) or laparoscopic APF ( n = 12 ) . Preoperative and postoperative stationary esophageal manometry included assessment of LES resting and postdeglutition relaxation pressures , intragastric pressure , and LES transient relaxations in the left lateral and upright positions and after gastric distension . RESULTS Both types of fundoplication result ed in significant increases in LES resting ( P < 0.001 ) and postdeglutition relaxation pressure ( P < 0.001 ) in both positions and after gastric distention . Intragastric pressure increased only after Nissen fundoplication in the postgastric distention state ( P = 0.01 ) . Transient LES relaxations were equally abolished after both procedures . All postoperative changes were to a similar level after either procedure with the exception of intragastric pressure after gastric distention , which was significantly higher after total than after partial fundoplication ( P = 0.04 ) . CONCLUSIONS Both procedures equally increase LES resting and postdeglutition relaxation pressures and abolish transient LES relaxations at all states . The significantly higher intragastric pressure at the postgastric distention state after Nissen fundoplication could possibly explain the higher incidence of epigastric fullness and discomfort after this type of antireflux surgery In the operative management of gastro‐oesophageal reflux , a balance must be achieved between adequate control of reflux and excessive dysphagia . The ideal technique is not known . A r and omized study was performed to determine whether laparoscopic anterior fundoplication is associated with a lower incidence of postoperative dysphagia than laparoscopic Nissen fundoplication , while achieving equivalent control of reflux How best to surgically treat GERD is an unresolved issue . To increase our insights into the fundoplication procedures , functional consequences for the gastroesophageal junction of an anterior or a posterior partial fundoplication were studied by manometry . Patients were r and omly selected from a larger study in a r and omised comparison between posterior and anterior partial fundoplications . The manometric studies were done 12 months after respective procedures in 24 patients . The motor characteristics of the esophagus and lower esophageal sphincter ( LES ) function were determined by use of sleeve catheter manometry . The manometric characteristics of the esophageal body were similar in the study groups except for the ramp pressure . This was significantly higher in patients with posterior partial fundoplications . The posterior group had significantly longer total length ( P < 0.02 ) as well as longer intra-abdominal portions ( P = 0.07 ) of the LES while the basal tone , albeit numerically higher , did not reach statistical significance . Water-swallow induced LES relaxations reached lower nadir values in the anterior group ( 1.7 vs 2.7 mmHg ) . Gas distension triggered few transient LES relaxations in both study groups while common cavities were more frequently observed in those having an anterior partial wrap ( P < 0.01 ) . A posterior partial fundoplication is followed by manometric characteristics suggesting a well functioning antireflux barrier with some obstruction to bolus passage as well as restricted venting of air from the stomach . The manometric mechanisms behind the inferior reflux control achieved by a Watson type of anterior partial wrap has now been further eluci date BACKGROUND AND AIMS The purpose of this study was to determine whether esophageal dysmotility affects symptoms of gastroesophageal reflux disease or clinical outcome after laparoscopic fundoplication and whether esophagus motor function changes postoperatively . METHODS Two hundred patients with a history of long-st and ing gastroesophageal reflux disease were investigated by clinical assessment , upper gastrointestinal endoscopy , esophageal manometry , and 24-hour pH monitoring between May 1999 and May 2000 . Patients were stratified according to presence or absence of esophageal dysmotility ( each n = 100 ) and r and omized to either 360 degrees ( Nissen ) or 270 degrees ( Toupet ) fundoplication . At a 4-month postoperative follow-up , preoperative tests were repeated . RESULTS Preoperative esophageal dysmotility was associated with more severe reflux symptoms , more frequent resistance to medical treatment ( 64 % vs. 49 % ; P < 0.05 ) , and greater decrease in lower esophageal sphincter pressure ( 9.5 + /- 5.3 vs. 12.4 + /- 6.7 mm Hg ; P < 0.0005 ) compared with normal motility . Postoperatively , clinical outcome and reflux recurrence ( 21 % vs. 14 % ) were similar . Esophageal Output:	Esophageal acid exposure time and the prevalence of heartburn are higher after LAF compared with LPF . In the short-term this is counterbalanced by less severe dysphagia . However , dysphagia scores become similar in the long-term , with a persistent substantial increase in prevalence of heartburn and PPI use after LAF . The reoperation rate is twice as high after LAF as well , mainly due to re interventions for recurrent GERD .
MS21338	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND In ROCKET AF ( Rivaroxaban Once-Daily , Oral , Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation ) , a large r and omized , clinical trial , rivaroxaban was noninferior to warfarin in preventing stroke or systemic embolism in patients with atrial fibrillation . OBJECTIVE To determine the efficacy and safety of rivaroxaban compared with warfarin among vitamin K antagonist (VKA)-naive and VKA-experienced patients . DESIGN Prespecified subgroup analysis . ( Clinical Trials.gov : NCT00403767 ) . SETTING Global . PATIENTS 14,264 persons with atrial fibrillation . MEASUREMENTS Interaction of the relative treatment effect of rivaroxaban and warfarin on stroke or systemic embolism among VKA-naive and VKA-experienced patients . RESULTS Overall , 7897 ( 55.4 % ) patients were VKA-experienced and 6367 ( 44.6 % ) were VKA-naive . The effect of rivaroxaban versus warfarin on stroke or systemic embolism was consistent : Rates per 100 patient-years of follow-up were 2.32 versus 2.87 for VKA-naive patients ( hazard ratio [ HR ] , 0.81 [ 95 % CI , 0.64 to 1.03 ] ) and 1.98 versus 2.09 for VKA-experienced patients ( HR , 0.94 [ CI , 0.75 to 1.18 ] ; interaction P = 0.36 ) . During the first 7 days , rivaroxaban was associated with more bleeding than warfarin ( HR in VKA-naive patients , 5.83 [ CI , 3.25 to 10.44 ] , and in VKA-experienced patients , 6.66 [ CI , 3.83 to 11.58 ] ; interaction P = 0.53 ) . After 30 days , rivaroxaban was associated with less bleeding than warfarin in VKA-naive patients ( HR , 0.84 [ CI , 0.74 to 0.95 ] ) and similar bleeding in VKA-experienced patients ( HR , 1.06 [ CI , 0.96 to 1.17 ] ; interaction P = 0.003 ) . LIMITATION The trial was not design ed to detect differences in these subgroups . CONCLUSION The efficacy of rivaroxaban in VKA-experienced and VKA-naive patients was similar to that of the overall trial . There were more bleeding events within 7 days of study drug initiation with rivaroxaban , but after 30 days , rivaroxaban was associated with less bleeding in VKA-naive patients and similar bleeding in VKA-experienced patients . This information may be useful to clinicians considering a transition to rivaroxaban for patients receiving VKA therapy . PRIMARY FUNDING SOURCE Johnson & Johnson and Bayer HealthCare BACKGROUND Warfarin reduces the risk of stroke in patients with atrial fibrillation but increases the risk of hemorrhage and is difficult to use . Dabigatran is a new oral direct thrombin inhibitor . METHODS In this noninferiority trial , we r and omly assigned 18,113 patients who had atrial fibrillation and a risk of stroke to receive , in a blinded fashion , fixed doses of dabigatran--110 mg or 150 mg twice daily -- or , in an unblinded fashion , adjusted-dose warfarin . The median duration of the follow-up period was 2.0 years . The primary outcome was stroke or systemic embolism . RESULTS Rates of the primary outcome were 1.69 % per year in the warfarin group , as compared with 1.53 % per year in the group that received 110 mg of dabigatran ( relative risk with dabigatran , 0.91 ; 95 % confidence interval [ CI ] , 0.74 to 1.11 ; P<0.001 for noninferiority ) and 1.11 % per year in the group that received 150 mg of dabigatran ( relative risk , 0.66 ; 95 % CI , 0.53 to 0.82 ; P<0.001 for superiority ) . The rate of major bleeding was 3.36 % per year in the warfarin group , as compared with 2.71 % per year in the group receiving 110 mg of dabigatran ( P=0.003 ) and 3.11 % per year in the group receiving 150 mg of dabigatran ( P=0.31 ) . The rate of hemorrhagic stroke was 0.38 % per year in the warfarin group , as compared with 0.12 % per year with 110 mg of dabigatran ( P<0.001 ) and 0.10 % per year with 150 mg of dabigatran ( P<0.001 ) . The mortality rate was 4.13 % per year in the warfarin group , as compared with 3.75 % per year with 110 mg of dabigatran ( P=0.13 ) and 3.64 % per year with 150 mg of dabigatran ( P=0.051 ) . CONCLUSIONS In patients with atrial fibrillation , dabigatran given at a dose of 110 mg was associated with rates of stroke and systemic embolism that were similar to those associated with warfarin , as well as lower rates of major hemorrhage . Dabigatran administered at a dose of 150 mg , as compared with warfarin , was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage . ( Clinical Trials.gov number , NCT00262600 . BACKGROUND Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects . The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known . METHODS We conducted a r and omized , double-blind , double-dummy trial comparing two once-daily regimens of edoxaban with warfarin in 21,105 patients with moderate-to-high-risk atrial fibrillation ( median follow-up , 2.8 years ) . The primary efficacy end point was stroke or systemic embolism . Each edoxaban regimen was tested for noninferiority to warfarin during the treatment period . The principal safety end point was major bleeding . RESULTS The annualized rate of the primary end point during treatment was 1.50 % with warfarin ( median time in the therapeutic range , 68.4 % ) , as compared with 1.18 % with high-dose edoxaban ( hazard ratio , 0.79 ; 97.5 % confidence interval [ CI ] , 0.63 to 0.99 ; P<0.001 for noninferiority ) and 1.61 % with low-dose edoxaban ( hazard ratio , 1.07 ; 97.5 % CI , 0.87 to 1.31 ; P=0.005 for noninferiority ) . In the intention-to-treat analysis , there was a trend favoring high-dose edoxaban versus warfarin ( hazard ratio , 0.87 ; 97.5 % CI , 0.73 to 1.04 ; P=0.08 ) and an unfavorable trend with low-dose edoxaban versus warfarin ( hazard ratio , 1.13 ; 97.5 % CI , 0.96 to 1.34 ; P=0.10 ) . The annualized rate of major bleeding was 3.43 % with warfarin versus 2.75 % with high-dose edoxaban ( hazard ratio , 0.80 ; 95 % CI , 0.71 to 0.91 ; P<0.001 ) and 1.61 % with low-dose edoxaban ( hazard ratio , 0.47 ; 95 % CI , 0.41 to 0.55 ; P<0.001 ) . The corresponding annualized rates of death from cardiovascular causes were 3.17 % versus 2.74 % ( hazard ratio , 0.86 ; 95 % CI , 0.77 to 0.97 ; P=0.01 ) , and 2.71 % ( hazard ratio , 0.85 ; 95 % CI , 0.76 to 0.96 ; P=0.008 ) , and the corresponding rates of the key secondary end point ( a composite of stroke , systemic embolism , or death from cardiovascular causes ) were 4.43 % versus 3.85 % ( hazard ratio , 0.87 ; 95 % CI , 0.78 to 0.96 ; P=0.005 ) , and 4.23 % ( hazard ratio , 0.95 ; 95 % CI , 0.86 to 1.05 ; P=0.32 ) . CONCLUSIONS Both once-daily regimens of edoxaban were noninferior to warfarin with respect to the prevention of stroke or systemic embolism and were associated with significantly lower rates of bleeding and death from cardiovascular causes . ( Funded by Daiichi Sankyo Pharma Development ; ENGAGE AF-TIMI 48 Clinical Trials.gov number , NCT00781391 . ) BACKGROUND Stroke and systemic thromboembolism are serious problems for patients with atrial fibrillation ( AF ) , but their incidence can be substantially reduced by appropriate anticoagulation . Bleeding is the major complication of anticoagulant treatment , and the relative risks for bleeding vs stroke must be considered when starting anticoagulation . METHODS The AFFIRM trial included patients with AF and at least one risk factor for stroke , r and omly assigning them to either a rate-control or rhythm-control strategy . All patients were initially treated with warfarin . The incidence of protocol -defined major and minor bleeding was documented during follow-up . Variables associated with bleeding were determined using a Cox proportional hazards model , using baseline and time-dependent covariates . RESULTS The 4060 patients in the AFFIRM trial were followed for an average of 3.5 years . Major bleeding occurred in 260 patients , an annual incidence of approximately 2 % per year , with no significant difference between the rate-control and rhythm-control groups . Increased age , heart failure , hepatic or renal disease , diabetes , first AF episode , warfarin use , and aspirin use were significantly associated with major bleeding . Minor bleeding was common in both treatment arms , with 738 patients reporting this problem in one or more visits . CONCLUSIONS Bleeding is a significant problem that complicates management of patients with AF . Risk factors for bleeding can be identified , and knowledge of these risk factors can be used to plan therapy CONTEXT In patients with nonvalvular atrial fibrillation , warfarin prevents ischemic stroke , but dose adjustment , coagulation monitoring , and bleeding limit its use . OBJECTIVE To compare the efficacy of the oral direct thrombin inhibitor ximelagatran with warfarin for prevention of stroke and systemic embolism . DESIGN , SETTING , AND PARTICIPANTS Double-blind , r and omized , multicenter trial ( 2000 - 2001 ) conducted at 409 North American sites , involving 3922 patients with nonvalvular atrial fibrillation and additional stroke risk factors . INTERVENTIONS Adjusted-dose warfarin ( aim ing for an international normalized ratio [ INR ] 2.0 to 3.0 ) or fixed-dose oral ximelagatran , 36 mg twice daily . MAIN OUTCOME MEASURES The primary end point was all strokes ( ischemic or hemorrhagic ) and systemic embolic events . The primary analysis was based on demonstrating noninferiority within an absolute margin of 2.0 % per year according to the intention-to-treat model . RESULTS During 6405 patient-years ( mean 20 months ) of follow-up , 88 patients experienced primary events . The mean ( SD ) INR with warfarin ( 2.4 [ 0.8 ] ) was within target during 68 % of the treatment period . The primary event rate with ximelagatran was 1.6 % per year and with warfarin was 1.2 % per year ( absolute difference , 0.45 % per year ; 95 % confidence interval , -0.13 % to 1.03 % per year ; P<.001 for the predefined noninferiority hypothesis ) . When all-cause mortality was included in addition to stroke and systemic embolic events , the rate difference was 0.10 % per year ( 95 % confidence interval , -0.97 % to 1.2 % per year ; P = .86 ) . There was no difference between treatment groups in rates of major bleeding , but total bleeding ( major and minor ) was lower with ximelagatran ( 37 % vs 47 % per year ; 95 % confidence interval for the difference , -14 % to -6.0 % per year ; P<.001 ) . Serum alanine aminotransferase levels rose to greater than 3 times the upper limit of normal in 6. Output:	In conclusion , use of dabigatran in prior VKA users in clinical practice was associated with a slightly increased risk of arterial thromboembolism and gastrointestinal bleeding , but a decreased risk of intracranial bleeding .
MS21339	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: PURPOSE To evaluate the clinical performance of Helioseal-F , a fluoride-containing fissure sealant , in school children at caries risk . MATERIAL S AND METHODS A caries risk assessment based on past caries experience , saliva microbial tests , buffer capacity and frequency of sugar intake was carried out in 204 healthy children , 6 - 7 years of age . Children exhibiting one or more risk factors were considered at caries risk ( n = 121 ) and their permanent molars were sealed with a fluoride-containing fissure sealant , thus forming a fissure sealant group ( FSG ) . The remaining 83 children with low caries risk received no fissure sealants and constituted a reference group ( RG ) . Both groups were followed for 2 years . From 15 children of both groups , unstimulated whole saliva was collected 1 month after sealant placement in order to determine fluoride levels . In another 20 children , a split-mouth study design was utilized to compare the colonization of mutans streptococci adjacent to and on F-containing sealants and conventional controls . The sealants were placed by dental hygienists according to the manufacturers ' instructions . RESULTS A total of 431 fissure sealants were placed at baseline . Complete retention was found in 76.6 % during the study period while 22.0 % were partially lost . Six sealants ( 1.4 % ) were completely lost . The enamel caries incidence was 45 % lower ( P < 0.05 ) in the permanent molars of the caries risk FSG compared with the low risk RG . There was no significant increase in saliva fluoride concentration following placement of the sealants and the proportion of mutans streptococci in relation to total viable counts was unaffected by type of material . The levels of salivary mutans streptococci were mainly unchanged in both groups during the study period , while the levels of salivary lactobacilli decreased in the FSG The aim of this study was to compare the retention and caries preventive efficacy of glass ionomer ( Fuji III ; GIC ) and light-cured resin-based ( Delton ; LCR ) fissure sealants . One hundred and sixty-six 5 - 14-year-old schoolchildren received sealants on their newly erupted first or second molars ; a split mouth design was used . Previously reported 2-year results showed low retention rates for GIC sealants , but no difference in the caries increment between the groups . The same persons were invited to a dental check-up 6.1 to 7.8 ( mean 7.1 ) years after the application of sealants ; 111 persons ( 66.8 % of the original group ) participated in the study . The retention of sealants , and the caries status of occlusal surfaces and adjacent proximal surfaces was recorded . On the sealed occlusal surfaces , 10 % of GIC and 45 % of LCR sealants were totally and 9 % of GIC and 20 % of LCR sealants partially present . Twenty-three ( 23.5 % ) of the occlusal surfaces sealed with GIC and 16 ( 16.5 % ) of those sealed with LCR were carious or filled . Compared to LCR sealants , the effectiveness of GIC sealants was -44 % ( 95 % CI -71 % , -16 % ) and net gain -7 % ( 95 % CI -18 % , 4 % ) . The relative risk of caries occurring was 1.44 ( 95 % CI 0.96 , 2.14 ) Output:	Sealing is a recommended procedure to prevent caries of the occlusal surfaces of permanent molars .
MS21340	*TASK* the task is to summarize an input biomedical literature in six sentences *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 compare the efficacy and safety of fluconazole and amphotericin B as empiric antifungal therapy of febrile neutropenic patients with cancer . PATIENTS AND METHODS A total of 317 neutropenic patients ( < 500 cells/mm3 ) with persistent or recrudescent fever despite 4 or more days of antibacterial therapy were r and omly assigned to receive either fluconazole ( 400 mg intravenously once daily ) or amphotericin B ( 0.5 mg/kg once daily ) . Patients were evaluated for the efficacy and safety of each drug by clinical criteria , frequent cultures and radiological procedures , and laboratory values . A response was classified as satisfactory at the end of therapy if the patient was afebrile , had no clinical or microbiological evidence of fungal infection , and did not require study termination due to lack of efficacy , drug toxicity , or death . RESULTS A satisfactory response occurred in 68 % of the patients treated with fluconazole ( 107 of 158 patients ) and in 67 % of patients treated with amphotericin B ( 106 of 159 patients ) . Progressive or new fungal infections during therapy occurred in 13 ( 8 % ) patients treated with fluconazole ( 8 with C and ida , 5 with Aspergillus ) and in 10 ( 6 % ) patients treated with amphotericin B ( 5 with C and ida , 3 with Aspergillus , 2 with other fungi ) . Adverse events related to study drug ( especially fever , chills , renal insufficiency , electrolyte disturbances , and respiratory distress ) occurred more often in patients treated with amphotericin B ( 128 [ 81 % ] of 159 patients ) than patients treated with fluconazole ( 20 [ 13 % ] of 158 patients , P = 0.001 ) . Eleven ( 7 % ) patients treated with amphotericin B but only 1 ( 1 % ) patient treated with fluconazole were terminated from the study owing to an adverse event ( P = 0.005 ) . Overall mortality ( 27 [ 17 % ] patients treated with fluconazole versus 34 [ 21 % ] patients treated with amphotericin B ) and mortality from fungal infection ( 7 [ 4 % ] patients treated with fluconazole versus 5 [ 3 % ] patients treated with amphotericin B ) were similar in each study group . CONCLUSIONS Intravenous fluconazole can be an effective and safe alternative to amphotericin B for empiric antifungal therapy in many febrile neutropenic patients . However , because fluconazole may be ineffective in the treatment of Aspergillus , patients at risk for that infection should be evaluated by chest radiograph , computed tomographic scanning , and cultures before the use of empiric fluconazole therapy BACKGROUND Voriconazole is a broad-spectrum triazole that is active against aspergillus species . We conducted a r and omized trial to compare voriconazole with amphotericin B for primary therapy of invasive aspergillosis . METHODS In this r and omized , unblinded trial , patients received either intravenous voriconazole ( two doses of 6 mg per kilogram of body weight on day 1 , then 4 mg per kilogram twice daily for at least seven days ) followed by 200 mg orally twice daily or intravenous amphotericin B deoxycholate ( 1 to 1.5 mg per kilogram per day ) . Other licensed antifungal treatments were allowed if the initial therapy failed or if the patient had an intolerance to the first drug used . A complete or partial response was considered to be a successful outcome . RESULTS A total of 144 patients in the voriconazole group and 133 patients in the amphotericin B group with definite or probable aspergillosis received at least one dose of treatment . In most of the patients , the underlying condition was allogeneic hematopoietic-cell transplantation , acute leukemia , or other hematologic diseases . At week 12 , there were successful outcomes in 52.8 percent of the patients in the voriconazole group ( complete responses in 20.8 percent and partial responses in 31.9 percent ) and 31.6 percent of those in the amphotericin B group ( complete responses in 16.5 percent and partial responses in 15.0 percent ; absolute difference , 21.2 percentage points ; 95 percent confidence interval , 10.4 to 32.9 ) . The survival rate at 12 weeks was 70.8 percent in the voriconazole group and 57.9 percent in the amphotericin B group ( hazard ratio , 0.59 ; 95 percent confidence interval , 0.40 to 0.88 ) . Voriconazole-treated patients had significantly fewer severe drug-related adverse events , but transient visual disturbances were common with voriconazole ( occurring in 44.8 percent of patients ) . CONCLUSIONS In patients with invasive aspergillosis , initial therapy with voriconazole led to better responses and improved survival and result ed in fewer severe side effects than the st and ard approach of initial therapy with amphotericin BACKGROUND Aspergillosis therapy with amphotericin , azoles , or echinoc and ins is associated with substantial mortality , ranging from 30 % to 80 % , depending on the stage of infection and the host 's underlying disease . The results of in vitro studies and animal models suggest that combination therapy with azoles and echinoc and ins may have additive activity against Aspergillus species . METHODS We evaluated the outcomes of patients with aspergillosis who experienced failure of initial therapy with amphotericin B formulations and received either voriconazole ( n=31 ) or a combination of voriconazole and caspofungin ( n=16 ) for salvage therapy . RESULTS The combination of voriconazole and caspofungin was associated with improved 3-month survival rate , compared with voriconazole alone ( hazard ratio [ HR ] , 0.42 ; 95 % confidence interval [ CI ] , 0.17 - 1.1 ; P=.048 ) . In multivariable models , salvage therapy with the combination of voriconazole and caspofungin was associated with reduced mortality , compared with therapy with voriconazole ( HR , 0.28 ; 95 % CI , 0.28 - 0.92 ; P=.011 ) , independent of other prognostic variables ( e.g. , receipt of transplant and type of conditioning therapy ) . The probability of death due to aspergillosis was lowest in patients who received the combination regimen . CONCLUSIONS R and omized trials are warranted to determine whether this combination should be used as primary therapy for aspergillosis Background : Invasive c and idiasis is increasingly prevalent in premature infants and seriously ill children , and pediatric data on available antifungal therapies are lacking . Methods : We conducted a pediatric sub study as part of a double-blind , r and omized , multinational trial to compare micafungin ( 2 mg/kg ) with liposomal amphotericin B ( 3 mg/kg ) as first-line treatment of invasive c and idiasis . Treatment success was defined as clinical and mycologic response at the end of therapy . Statistical analyses were descriptive , as the sample size meant that the study was not powered for hypothesis testing . Results : One hundred six patients were included in the intent-to-treat population ; and 98 patients —48 patients in the micafungin group and 50 patients in the liposomal amphotericin B group — in the modified intent-to-treat population . Baseline characteristics were balanced between treatment groups . Overall , 57 patients were < 2 years old including 19 patients who were premature at birth ; and 41 patients were 2 to < 16 years old . Most patients ( 91/98 , 92.9 % ) had c and idemia , and 7/98 ( 7.1 % ) patients had other forms of invasive c and idiasis . Treatment success was observed for 35/48 ( 72.9 % ) patients treated with micafungin and 38/50 ( 76.0 % ) patients treated with liposomal amphotericin B. The difference in proportions adjusted for neutropenic status was −2.4 % [ 95 % CI : ( −20.1 to 15.3 ) ] . Efficacy findings were consistent , independent of the neutropenic status , the age of the patient , and whether the patient was premature at birth . Both treatments were well tolerated , but with a lower incidence of adverse events that led to discontinuation in the micafungin group ( 2/52 , 3.8 % ) compared with the liposomal amphotericin B group ( 9/54 , 16.7 % ) ( P = 0.05 , Fisher exact test ) . Conclusions : Micafungin seems to be similarly effective and as safe as liposomal amphotericin B for the treatment of invasive c and idiasis in pediatric patients . ( Clinical Trials.gov number , NCT00106288 ) The epidemiology , management , and long-term survival of invasive aspergillosis was assessed in a prospect i ve , 5-year observational study in 346 unselected paediatric cancer patients receiving dose-intensive chemotherapy for newly diagnosed or recurrent malignancies . Invasive aspergillosis occurred exclusively in the context of haematological malignancies , where it accounted for an incidence of 6.8 % ( n = 13 of 189 ) . The lung was the primary site in 12 cases , and dissemination was present in three of those . Prior to diagnosis , the overwhelming majority of patients had been profoundly neutropenic for at least 14 days ( n = 11 of 13 ) and were receiving systemic antifungal agents ( n = 10 of 13 ) . Clinical signs and symptoms were nonspecific but always included fever . All 11 patients who were diagnosed and treated during lifetime for a minimum of 10 days responded to either medical or combined medical and surgical treatment , and seven were cured ( 64 % ) . Nevertheless , the overall long-term survival was merely 31 % after a median follow-up of 5.68 years after diagnosis . Apart from refractory or recurrent cancer , the main obstacles to successful outcome were failure to diagnose IA during lifetime and bleeding complications in patients with established diagnosis . The frequency of invasive aspergillosis of greater than 15 % in paediatric patients with acute myeloblastic leukaemia and recurrent leukaemias warrants the systematic investigation of preventive strategies in these highly vulnerable subgroups Coccidioidomycosis is a systemic fungal infection caused by Coccidioides immitis . Typically , infection stimulates a protective immune response that limits the initial illness and confers lifelong resistance to subsequent infections ( 1 ) . Occasionally , however , illness progresses , either as a fibrocavitary chronic pneumonia or hematogenously , with dissemination of infection to such extrathoracic sites as the skin , bones , or joints ( 2 , 3 ) . If these complications occur , antifungal therapy is warranted to prevent further tissue destruction and associated morbidity ( 4 ) . Azole antifungal agents have become valuable in treating progressive forms of coccidioidomycosis , especially when disease manifestations are not fulminant or immediately life-threatening . Originally , the U.S. Food and Drug Administration approved intravenous miconazole and oral ketoconazole for this indication on the basis of their efficacy and safety ( 5 - 14 ) . The lack of an oral form of miconazole and untoward effects or drug intolerance related to both agents led to the development of fluconazole , itraconazole , and related congeners . These new drugs have shown therapeutic efficacy against coccidioidomycosis in experimental infections of animals ( 15 - 20 ) and in subsequent clinical trials ( 21 - 30 ) . Our current underst and ing of optimal management of coccidioidal infections is severely limited by the absence of r and omized comparative trials that evaluate the different forms of therapy . Multicenter comparative trials are now possible because over the past decade , the evaluation of patients treated for coccidioidomycosis has become st and ardized . In addition , because of the development of a collaborative group during the same period , trials can now enroll enough patients to support clinical ly applicable results . In this report , we present the findings from Mycoses Study Group Protocol 20 , a comparative trial sponsored by the National Institute of Allergy and Infectious Diseases that compares two antifungal agents , fluconazole and itraconazole , in the treatment of coccidioidomycosis . Methods Patient Eligibility Patients were considered for enrollment if C. immitis was identified by culture , by microscopic examination of infected tissue from outside the lungs , or from respiratory specimens , if a pulmonary infection had persisted for more than 3 months . Patients with HIV infection and pulmonary coccidioidomycosis of shorter duration were eligible if their CD4 count was less than or equal to 0.25 109 cells/L or if they had diffuse bilateral pneumonia . Enrollees had to be able to take oral medications . Pregnant women were excluded , and women of childbearing potential were required to practice an effective method of birth control Output:	No difference in breakthrough fungal infection was observed in children with prolonged fever and neutropenia . Limited paediatric data are available comparing antifungal agents in children with proven , probable or suspected invasive fungal infection . No differences in mortality or treatment efficacy were observed when antifungal agents were compared .
MS21341	*TASK* the task is to summarize an input biomedical literature in six sentences *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 evaluated the contribution of sentinel-node biopsy to outcomes in patients with newly diagnosed melanoma . METHODS Patients with a primary cutaneous melanoma were r and omly assigned to wide excision and postoperative observation of regional lymph nodes with lymphadenectomy if nodal relapse occurred , or to wide excision and sentinel-node biopsy with immediate lymphadenectomy if nodal micrometastases were detected on biopsy . RESULTS Among 1269 patients with an intermediate-thickness primary melanoma , the mean ( + /-SE ) estimated 5-year disease-free survival rate for the population was 78.3+/-1.6 % in the biopsy group and 73.1+/-2.1 % in the observation group ( hazard ratio for recurrence[corrected ] , 0.74 ; 95 % confidence interval [ CI ] , 0.59 to 0.93 ; P=0.009 ) . Five-year melanoma-specific survival rates were similar in the two groups ( 87.1+/-1.3 % and 86.6+/-1.6 % , respectively ) . In the biopsy group , the presence of metastases in the sentinel node was the most important prognostic factor ; the 5-year survival rate was 72.3+/-4.6 % among patients with tumor-positive sentinel nodes and 90.2+/-1.3 % among those with tumor-negative sentinel nodes ( hazard ratio for death , 2.48 ; 95 % CI , 1.54 to 3.98 ; P<0.001 ) . The incidence of sentinel-node micrometastases was 16.0 % ( 122 of 764 patients ) , and the rate of nodal relapse in the observation group was 15.6 % ( 78 of 500 patients ) . The corresponding mean number of tumor-involved nodes was 1.4 in the biopsy group and 3.3 in the observation group ( P<0.001 ) , indicating disease progression during observation . Among patients with nodal metastases , the 5-year survival rate was higher among those who underwent immediate lymphadenectomy than among those in whom lymphadenectomy was delayed ( 72.3+/-4.6 % vs. 52.4+/-5.9 % ; hazard ratio for death , 0.51 ; 95 % CI , 0.32 to 0.81 ; P=0.004 ) . CONCLUSIONS The staging of intermediate-thickness ( 1.2 to 3.5 mm ) primary melanomas according to the results of sentinel-node biopsy provides important prognostic information and identifies patients with nodal metastases whose survival can be prolonged by immediate lymphadenectomy . ( Clinical Trials.gov number , NCT00275496 [ Clinical Trials.gov ] . ) PURPOSE Low-dose ( LD ) interferon ( IFN ) alfa ( LDI ) has demonstrated a consistent disease-free survival benefit for patients with clinical ly lymph node-negative melanoma in clinical trials . However , the optimal duration of treatment is still under discussion , and no previous trial has evaluated this question specifically . A prolongation of LDI from 18 months to 60 months might be of clinical benefit for patients with intermediate or high-risk melanoma . PATIENTS AND METHODS Eight hundred fifty patients with resected cutaneous melanoma of at least 1.5 mm tumor thickness were included in this prospect i ve r and omized , multicenter trial in Germany and Austria . Patients had to be clinical ly lymph node-negative , and sentinel node biopsy ( SLNB ) was performed in a majority of cases . They were r and omly assigned to receive 3 MU IFNalpha2a three times a week subcutaneously for either 18 months ( arm A ) or 60 months ( arm B ) . Results Of 850 r and omly assigned patients , 840 were eligible for evaluation after a median follow-up of 4.3 years . Tumor thickness and other relevant prognostic factors were well balanced between both groups . SLNB was performed in 635 patients ( 75.6 % ) , with a positivity rate of 18.0 % in arm A and 17.5 % in arm B. Neither relapse-free survival ( arm A , 75.6 % v arm B , 72.6 % ; P = .72 ; hazard ratio , 1.05 ; 95 % CI , 0.80 to 1.39 ) nor distant-metastasis-free survival ( 81.9 % v 79.7 % ; P = .56 ; HR , 1.10 ; 95 % CI , 0.80 to 1.52 ) or overall survival ( 85.9 % v 84.9 % ; P = .86 ; HR , 1.03 ; 95 % CI , 0.71 to 1.50 ) showed significant differences . CONCLUSION A prolongation of conventional LDI therapy from 18 to 60 months showed no clinical benefit in patients with intermediate and high-risk primary melanoma The propensity score is the probability of treatment assignment conditional on observed baseline characteristics . The propensity score allows one to design and analyze an observational ( nonr and omized ) study so that it mimics some of the particular characteristics of a r and omized controlled trial . In particular , the propensity score is a balancing score : conditional on the propensity score , the distribution of observed baseline covariates will be similar between treated and untreated subjects . I describe 4 different propensity score methods : matching on the propensity score , stratification on the propensity score , inverse probability of treatment weighting using the propensity score , and covariate adjustment using the propensity score . I describe balance diagnostics for examining whether the propensity score model has been adequately specified . Furthermore , I discuss differences between regression-based methods and propensity score-based methods for the analysis of observational data . I describe different causal average treatment effects and their relationship with propensity score analyses Objective : The objective of this study was to evaluate , in an international multicenter phase III trial , the accuracy , use , and morbidity of intraoperative lymphatic mapping and sentinel node biopsy ( LM/SNB ) for staging the regional nodal basin of patients with early-stage melanoma . Summary Background Data : Since our introduction of LM/SNB in 1990 , this technique has been widely adopted and has become part of the American Joint Committee on Cancer ( AJCC ) staging system . Eleven years ago , the authors began the international Multicenter Selective Lymphadenectomy Trial ( MSLT-I ) to compare 2 treatment approaches : wide excision ( WE ) plus LM/SNB with immediate complete lymphadenectomy ( CLND ) for sentinel node ( SN ) metastases , and WE plus postoperative observation with CLND delayed until the subsequent development of clinical ly evident nodal metastases . Methods : After each center achieved 85 % accuracy of SN identification during a 30-case learning phase , patients with primary cutaneous melanoma ( ≥1 mm with Clark level ≥III , or any thickness with Clark level ≥IV ) were r and omly assigned in a 4:6 ratio to WE plus observation ( WEO ) with delayed CLND for nodal recurrence , or to WE plus LM/SNB with immediate CLND for SN metastasis . The accuracy of LM/SNB was determined by comparing the rates of SN identification and the incidence of SN metastases in the LM/SNB group versus the subsequent development of nodal metastases in the regional nodal basin of those patients with tumor-negative SNs . Early morbidity of LM/SNB was evaluated by comparing complication rates between the 2 treatment groups . Trial accrual was completed on March 31 , 2002 , after enrollment of 2001 patients . Results : Initial SN identification rate was 95.3 % overall : 99.3 % for the groin , 95.3 % for the axilla , and 84.5 % for the neck basins . The rate of false-negative LM/SNB during the trial phase , as measured by nodal recurrence in a tumor-negative dissected SN basin , decreased with increasing case volume at each center : 10.3 % for the first 25 cases versus 5.2 % after 25 cases . There were no operative mortalities . The low ( 10.1 % ) complication rate after LM/SNB increased to 37.2 % with the addition of CLND ; CLND also increased the severity of complications . Conclusions : LM/SNB is a safe , low-morbidity procedure for staging the regional nodal basin in early melanoma . Even after a 30-case learning phase and 25 additional LM/SNB cases , the accuracy of LM/SNB continues to increase with a center 's experience . LM/SNB should become st and ard care for staging the regional lymph nodes of patients with primary cutaneous melanoma Background In the United Kingdom ( UK ) , there is an extensive market for the class ' A ' drug heroin . Many heroin users spend time in prison . People addicted to heroin often require prescribed medication when attempting to cease their drug use . The most commonly used detoxification agents in UK prisons are buprenorphine , dihydrocodeine and methadone . However , national guidelines do not state a detoxification drug of choice . Indeed , there is a paucity of research evaluating the most effective treatment for opiate detoxification in prisons . This study seeks to address the paucity by evaluating routinely used interventions amongst drug using prisoners within UK prisons . Methods / Design The Leeds Evaluation of Efficacy of Detoxification Study ( LEEDS ) Prisons Pilot Study will use r and omised controlled trial methodology to compare the open use of buprenorphine and dihydrocodeine for opiate detoxification , given in the context of routine care , within HMP Leeds . Prisoners who are eligible and give informed consent will be entered into the trial . The primary outcome measure will be abstinence status at five days post detoxification , as determined by a urine test . Secondary outcomes during the detoxification and then at one , three and six months post detoxification will be recorded 9603 Background : Emotional state has been linked to cancer survival , but its influence on the outcome of early melanoma is unclear . The Multicenter Selective Lymphadenectomy Trial ( MSLT-I ) r and omized patients with clinical ly localized cutaneous melanoma to wide local excision ( WEX ) plus observation or to WEX plus sentinel lymph node biopsy ( SNB ) . Clinical endpoints included disease-specific and disease-free survival . A sub study of this phase III trial evaluated the impact of mood state on survival , and the impact of recurrence on mood state . METHODS Patients were asked to complete a 65- question form within 6 months of enrollment ( baseline ) and every 12 months thereafter . This question naire measured 6 identifiable mood states ( vigor-activity , tension-anxiety , depression , anger-hostility , fatigue-inertia , confusion-bewilderment ) of the Profile of Mood States ( POMS ) , a vali date d mood scale for assessing responses to therapy . Self-reported data from the question naires were linked to demographic and clinical variables . RESULTS Of 2,001 patients accrued to MSLT-I , 1,620 completed the question naire at baseline . The baseline distribution of POMS variables was similar in the two treatment arms ( data not shown ) . Patients with more vigor at baseline had a significantly longer disease-free and overall survival ( Table ) , even after adjusting for age , tumor thickness , site , and ulceration status ( p < 0.001 ) . Among 136 patients who completed a question naire within 6 months after recurrence , comparison of baseline and post-recurrence responses revealed significant changes in mood state : tension , fatigue and confusion increased , whereas vigor decreased ( p = 0.0004 , 0.0171 , 0.0089 , and 0.0028 , respectively ) . CONCLUSIONS Vigor , a measure of energy and optimism , is directly correlated with disease-free and overall survival in early melanoma . The negative impact of recurrence on mood state suggests that SNB as a tool for preventing recurrence might also improve mood state and psychological well-being . Supported by NIH CA29605 . [ Table : see text ] No significant financial relationships to disclose BACKGROUND Sentinel-node biopsy , a minimally invasive procedure for regional melanoma staging , was evaluated in a phase 3 trial . METHODS We evaluated outcomes in 2001 patients with primary cutaneous melanomas r and omly assigned to undergo wide excision and nodal observation , with lymphadenectomy for nodal relapse ( observation group ) , or wide excision and sentinel-node biopsy , with immediate lymphadenectomy for nodal metastases detected on biopsy ( biopsy group ) . Results No significant treatment-related difference in the 10-year melanoma-specific survival rate was seen in the overall study population ( 20.8 % with and 79.2 % without nodal metastases ) . Mean ( ± SE ) 10-year disease-free survival rates were significantly improved in the biopsy group , as compared with the observation group , among patients with intermediate-thickness melanomas , defined as 1.20 to 3.50 mm ( 71.3 ± 1.8 % vs. 64.7 ± 2.3 % ; hazard ratio for recurrence or metastasis , 0.76 ; P=0.01 ) , and those with thick melanomas , defined as > 3.50 mm ( 50.7 ± 4.0 % vs. 40.5 ± 4.7 % ; hazard ratio , 0 Output:	We expect that overall survival data will be available in a future up date of this review .Disease-free survival and rate of local and regional recurrence favoured SLNB in both groups of participants with intermediate-thickness and thick melanomas but short-term surgical morbidity was higher in the SLNB group , especially with regard to complications in the nodal basin . Currently this evidence is not sufficient to document a benefit of SLNB when compared to observation in individuals with primary localised cutaneous melanoma
MS21342	*TASK* the task is to summarize an input biomedical literature in six sentences *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 : A prospect i ve r and omized trial was conducted to study the timing of high-dose intravenous melphalan and autologous stem cell transplantation ( HDM/SCT ) in AL amyloidosis . In all , 100 newly diagnosed patients were r and omized to receive HDM/SCT , either as initial therapy ( Arm-1 ) or following two cycles of oral melphalan and prednisone ( Arm-2 ) . The objectives of the trial were to compare survival and hematologic and clinical responses . With a median follow-up of 45 months ( range 24–70 ) , the overall survival was not significantly different between the two treatment arms ( P=0.39 ) . The hematologic response and organ system improvements after treatment did not differ between the two groups . Fewer patients received HDM/SCT in Arm-2 because of disease progression during the oral chemotherapy phase of the study , rendering them ineligible for subsequent high-dose therapy . This affected patients with cardiac involvement particularly , and led to a trend for an early survival disadvantage in Arm-2 . Hence , newly diagnosed patients with AL amyloidosis eligible for HDM/SCT did not benefit from initial treatment with oral melphalan and prednisone , and there was a survival disadvantage for patients with cardiac involvement if HDM/SCT was delayed by initial oral chemotherapy One hundred sixty-eight patients with primary systemic amyloidosis ( AL ) were identified . Median survival after diagnosis was 12 months and ranged from 4 months for patients presenting with congestive heart failure to 50 months for those presenting with peripheral neuropathy only . Utilizing the proportional-hazards model in a stepwise multivariate fashion to evaluate the simultaneous influence of putative risk factors as of diagnosis revealed that congestive heart failure , urine light chain , hepatomegaly , and multiple myeloma were the major factors adversely affecting survival during the first year after diagnosis . Serum creatinine , multiple myeloma , orthostatic hypotension , and monoclonal serum protein were the most important variables adversely affecting survival for patients surviving 1 year . These models were used to categorize patients according to the variables in the models into low- , moderate- , and high-risk groups for the first year after diagnosis and separately for subsequent years . The influence of these variables on survival is important in stratification of patients r and omized to prospect i ve clinical trials High‐dose melphalan ( MEL ) with autologous stem cell transplant ( SCT ) is an effective therapy for systemic AL amyloidosis ( AL ) , but treatment‐related mortality ( TRM ) has historically been high . We performed a phase II trial of risk‐adapted SCT followed by adjuvant dexamethasone ( dex ) and thalidomide ( thal ) in an attempt to reduce TRM and improve response rates . Patients ( n = 45 ) with newly diagnosed AL involving ≤2 organ systems were assigned to MEL 100 , 140 , or 200 mg/m2 with SCT , based on age , renal function and cardiac involvement . Patients with persistent clonal plasma cell disease 3 months post‐SCT received 9 months of adjuvant thal/dex ( or dex if there was a history of deep vein thrombosis or neuropathy ) . Organ involvement was kidney ( 67 % ) , heart ( 24 % ) , liver/GI ( 22 % ) and peripheral nervous system ( 18 % ) , with 31 % having two organs involved . TRM was 4·4 % . Thirty‐one patients began adjuvant therapy , with 16 ( 52 % ) completing 9 months of treatment and 13 ( 42 % ) achieving an improvement in haematological response . By intention‐to‐treat , overall haematological response rate was 71 % ( 36 % complete response ) , with 44 % having organ responses . With a median follow‐up of 31 months , 2‐year survival was 84 % ( 95 % confidence interval : 73 % , 94 % ) . Risk‐adapted SCT with adjuvant thal/dex is feasible and results in low TRM and high haematological and organ response rates in AL patients PURPOSE Based on the success of hematopoietic stem-cell transplantation ( HSCT ) for multiple myeloma , HSCT is being used to treat patients with primary systemic amyloidosis ( AL ) . This article addresses the extent to which eligibility to undergo HSCT is a favorable prognostic feature and explores prognostic factors within the subset of eligible patients . PATIENTS AND METHODS The Mayo Clinic amyloid data base was queried for all patients with AL seen at the Mayo Clinic from 1983 through 1997 who would have been eligible for peripheral-blood stem-cell transplantation . Inclusion criteria included biopsy-proven amyloid , symptomatic disease , absence of a clinical diagnosis of multiple myeloma , age < or = 70 years , cardiac interventricular septal thickness < or = 15 mm , cardiac ejection fraction more than 55 % , serum creatinine < or = 2 mg/dL , and direct bilirubin < or = 2.0 mg/dL. RESULTS Median age was 56 years ( range , 25 to 70 ) with 79 ( 34 % ) older than 60 years . One hundred patients had early cardiac involvement ; 41 , hepatic involvement ; 167 , renal involvement ; and 39 , nerve involvement . The 229 patients have had a median follow-up of 52 months , and 151 have died . The median survival was 42 months with 5- and 10-year survival rates of 36 % and 15 % , respectively . Important predictors of survival were size of M-component in 24-hour urine , number of involved organs , alkaline phosphatase , performance score , and weight loss . CONCLUSION The same patients who are eligible for HSCT are a good-risk population who do relatively well with chemotherapy ( median survival , 42 months ) , substantially better than the expected median survival of 18 months for all patients with AL . A r and omized trial is needed to assess the true effect of HSCT Current therapy of primary systemic ( AL ) amyloidosis with oral melphalan and prednisone remains unsatisfactory , with a median survival of only 13 months . Between 1996 and 2003 , 93 patients with biopsy-proven AL amyloidosis were enrolled in a prospect i ve US national cooperative group trial . Treatment schema consisted of induction therapy with pulse dexamethasone ( DEX ) , followed by maintenance therapy with DEX and alpha interferon . Hematologic complete remissions were observed in 24 % and improvement in AL amyloidosis-related organ dysfunction occurred in 45 % of patients evaluable for response . Median survival of the entire cohort is 31 months , with an estimated 2-year overall survival ( OS ) and event-free survival ( EFS ) of 60 % and 52 % , respectively . Presence of congestive heart failure and increased level of serum beta2 microglobulin ( > /= 0.0035 g/L [ 3.5 mg/L ] ) were dominant predictors of adverse outcome . Estimated 2-year OS in patients who are eligible to receive transplants with this approach was 78 % . These data demonstrate for the first time in the context of a US multicenter prospect i ve clinical trial that front-line therapy with a DEX-based regimen in AL amyloidosis can lead to durable reversal of AL amyloidosis-related organ dysfunction and prolonged survival This study investigated the response rate and toxicity of blood cell transplantation as treatment for primary amyloidosis ( AL ) . Twenty-three patients had stem cells collected between November 1995 and September 1998 . Conditioning included melphalan and total body irradiation in 16 and melphalan alone in 4 . Three patients did not undergo stem cell infusion because of poor performance status . Two died of progressive amyloid at 1 and 3 months . One patient is alive on hemodialysis . Fourteen males and six females ( median age , 57 years ) underwent transplantation . Renal , cardiac ( by echocardiography ) , peripheral neuropathy or liver amyloidosis occurred in 14 , 12 , 3 , and 1 , respectively . Echocardiography demonstrated an interventricular septal thickness ⩾15 mm in six patients , five of whom died post transplantation . Three patients died of progressive amyloidosis at 7 , 7 , and 21 months . Thirteen patients are alive with a follow-up of 3 to 26 months . Twelve ( 60 % ) fulfilled the criteria of a hematologic or organ response . Severe gastrointestinal tract toxicity was seen in five ( 25 % ) . We conclude that blood cell transplantation for amyloidosis had a much higher morbidity and mortality compared with transplantation for myeloma . The best results appear to occur in patients with nephrotic syndrome as the only manifestation of their disease . Bone Marrow Transplantation ( 2000 ) 26 , 963–969 Context AL amyloidosis responds poorly to oral chemotherapy and rarely leads to elimination of plasma cell dyscrasia . Amyloid cardiomyopathy is a particularly fatal complication of the disease . Contribution Analysis of consecutive patients with AL amyloidosis from 6 separate trials over 8 years shows that high-dose intravenous melphalan therapy combined with autologous stem-cell transplantation greatly improves duration of survival and ameliorates organ dysfunction . Implication s Intravenous melphalan therapy combined with stem-cell transplantation represents a clinical ly significant improvement in treating AL amyloidosis and shows promise in reversing amyloid cardiomyopathy . The Editors The most common form of systemic amyloidosis in the United States is AL ( or primary ) amyloidosis . In this disease , amyloid fibrils are derived from monoclonal immunoglobulin light chains that are produced by an underlying clonal plasma cell dyscrasia . Although the burden of plasma cells is generally low , accumulation of amyloid deposits in vital organs leads to progressive disability and death . The median survival of untreated patients after diagnosis is 12 months and less than 5 months for those with cardiomyopathy ( 1 - 5 ) . AL amyloidosis is reported to occur in 5 to 12 persons per million per year in the United States ; however , death records and autopsy results suggest that the incidence may be higher ( 6 , 7 ) . Treatment with oral melphalan results in a modest increase in median survival but rarely eliminates the plasma cell dyscrasia and is not effective for rapidly progressive disease ( 8 - 10 ) . Alternative chemotherapy regimens have not improved survival further ( 11 - 15 ) . Promising treatment outcomes observed with high-dose intravenous melphalan and autologous stem-cell transplantation in multiple myeloma ( 16 - 19 ) provided a rationale for testing the hypothesis that this treatment would improve survival for patients with AL amyloidosis . Favorable responses to high-dose melphalan and stem-cell transplantation in patients with AL amyloidosis have been reported in case reports and in small series ; however , treatment-related mortality was high in multicenter trials ( 20 - 28 ) . Our initial experience with treatment in AL amyloidosis indicated that selected patients can tolerate treatment and that hematologic responses and reversal of amyloid-related organ dysfunction can be achieved ( 29 - 32 ) . Since 1994 , we have evaluated 701 patients with AL amyloidosis , 312 of whom initiated high-dose melphalan treatment and stem-cell transplantation . This longitudinal study examines survival , hematologic response , and improvement of amyloid-related organ disease in patients who were treated with high-dose melphalan and stem-cell transplantation . We contrast these data with features and survival of a simultaneous cohort of patients who were not eligible for treatment . Methods Patients Between July 1994 and June 2002 , 701 consecutive patients with AL amyloidosis were evaluated and clinical data were collected with the approval of the Institutional Review Board of Boston University Medical Center . All patients had biopsy-proven amyloid disease and a documented plasma cell dyscrasia , which was diagnosed by the presence of clonal plasma cells in the bone marrow or a monoclonal gammopathy detected by immunofixation electrophoresis of serum or urine proteins ( Figure 1 ) . To exclude another type of systemic amyloidosis and a monoclonal gammopathy of unknown significance , all patients with findings compatible with familial or secondary ( AA ) amyloidosis were tested by DNA analysis for gene mutations in transthyretin , apolipoprotein A1 , fibrinogen , and lysozyme known to be associated with amyloidosis and by immunohistochemistry of the biopsy tissue for AA amyloid fibril deposits ( 33 ) . Patients with multiple myeloma ( bone marrow plasmacytosis 30 % or lytic bone lesions ) were excluded . In patients older than 70 years of age with cardiomyopathy only , a diagnosis of senile cardiac amyloidosis ( caused by wild-type transthyretin ) was excluded by immunohistochemical examination of a tissue biopsy specimen using antiserum to transthyretin . All patients were evaluated for degree of organ involvement by physical examination , st Output:	In the controlled studies , there was no heterogeneity for any outcome ; however , in the single-arm studies , there was a significant heterogeneity for the outcomes of OS , CHR , renal response , and partial hematologic response . Our findings indicate that AHCT does not appear to be superior to CC in improving OS in patients with AL amyloidosis .
MS21343	*TASK* the task is to summarize an input biomedical literature in six sentences *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 investigation was to examine selected psychobiological responses to acute bouts of resistance exercise ( RE ) of different intensities . METHODS Eighty-four participants were classified as experienced or inexperienced and then r and omly assigned to three conditions : 1 ) 50 % of one repetition maximum(1RM ) , 2 ) 80 % 1RM , or 3 ) control condition . RE consisted of performing three sets of four exercises between 12 to 20 reps in the 50 % 1RM condition and four to eight reps in the 80 % 1RM condition . Dependent variables consisted of state anxiety ( SA ) , mood states ( POMS ) , systolic BP ( SBP ) , diastolic BP ( DBP ) , and heart rate ( HR ) . These variables were assessed before as well as 1 , 20 , 60 , 120 , and 180-min following the conditions . Data were analyzed with a 2 ( experience ) x 3 ( conditions ) x 6 ( trials ) mixed model ANOVA and Tukey post-hoc tests . RESULTS Results indicated that SA decreased significantly ( P < 0.05 ) 180 min following the 50 % 1RM condition . A significant decrease ( P < 0.05 ) in vigor occurred immediately following the 50 % IRM condition and persisted for 20 min . SBP increased significantly ( P < 0.05 ) immediately following the 80 % 1RM condition . HR increased significantly ( P < 0.05 ) following both RE conditions . No significant differences were found between the experienced or inexperienced participants . CONCLUSIONS An acute bout of RE at 50 % 1RM is associated with an immediate reduction in vigor followed by a significant decrease in SA that emerged 180 min following exercise This study compared the physical and psychological effects of running to those of the normal physical education program of activities among 154 fourth , fifth , and sixth grade rs who were r and omly assigned to conditions within a true experimental design . The running program consisted of three 30-min sessions per week for 12 weeks in lieu of attendance in regular physical education classes . Findings showed that although boys tended to run faster than girls overall and that older children run faster than younger children , running-program participants performed better on an 800-m run , had lower pulse rates , and performed better on a test of creativity than did regular physical education participants . Running boys had less body fat , and running girls had more creative involvement in class . No differences were found on 50-m dash performance or perceptual skill . On total behavior , girls were more self-controlled than boys , and self-concept tended to become less positive with increased grade level . Running performance for 800 m persisted for 5 months among boys in the treatment , but not among girls . Running was judged effective for enhancing the cardiorespiratory health and creativity of school children Use of adventure as an intervention in traditional counseling was explored with 84 adolescent clients from two community-based counseling agencies and residents from two boys ' homes . The adolescents were assigned to conditions of counseling plus adventure experiences , counseling only , adventure only , or a control . Analysis indicated limited support for increasing self-esteem and social skills by adding adventure experiences to on-going counseling To determine whether participating in physical activity affects psychological well-being in an adolescent population , 147 adolescents completed self-reports of exercise and psychological stress and well-being . Analysis revealed that those who reported greater physical activity also reported less stress and lower levels of depression . Adolescents who experienced a higher incidence of life events also demonstrated a strong association between stress and anxiety/depression/hostility . To investigate the effects of exercise training on psychological well-being , adolescents were assigned to either high or moderate intensity aerobic training , flexibility training or a control group . The training groups met twice per week for 25 - 30 min . Aerobic fitness levels , heart rate , blood pressure and self-report of stress and well-being were measured prior to and following 10 weeks of training . Post-training fitness measures confirmed the effectiveness of the high intensity aerobic exercise and between groups differences for physiological and some psychological measures were found . Subjects undergoing high intensity exercise reported significantly less stress than subjects in the remaining three groups . The relationship between stress and anxiety/depression/hostility for the high intensity group was considerably weakened at the end of the training period . For the remaining subjects , however , this relationship was , if anything , strengthened . This experiment provides evidence to suggest that in an adolescent population , high intensity aerobic exercise has positive effects on well-being Aerobic exercise which result ed in a significant improvement in cardiovascular functioning had no more effect on psychological mood states than did the placebo control of participation in nonaerobic recreational games or no exercise and sport at all ( N = 430 college students ) . Beta-endorphin levels with the 41 depressed subjects were not a biochemical link that might explain the possible influence of physical activity on depression Abstract This study was design ed to assess the effects of a specifically design ed perceptual-motor training program on the level of perceptual-motor development , self-concept , and academic ability of kindergarten children . Subjects for the study were 40 kindergarten children r and omly assigned to 1 of 2 groups . Each group received the same kindergarten program with one exception , the experimental group was exposed to a specifically design ed perceptual-motor program 30 min daily for 5 mo , while the control group received a free play period for 30 min daily . Results of the study indicated that the data tended to support the specificity of training concept . The variables showing the greatest change were the perceptual-motor tests which measured changes on specific aspects of the training program . There appeared to be some immediate transfer to academic abilities but this was not pronounced enough to suggest that perceptual-motor training was of real benefit in developing academic abilities for normal kinderga The purpose of this study was to examine self-esteem changes in school aged children enrolled in weight management programs . The study group was comprised of 54 obese children ages 10 - 15 enrolled in a weight management program . The control group was comprised of 60 obese children who had never been enrolled in a weight management program . Each child was measured for body mass index ( BMI ) and weight . All the children filled out the Pier-Harris Children 's Self-Concept Scale at the beginning of the study and 12 weeks later following the study group 's completion of the weight management program . The groups were similar in average age , weight , BMI , and self-concept score at the beginning of the study . At the end of the 12 weeks , there was no significant change in the average weight or BMI in either the study or control group . There was a significant decrease in the self-concept score in the study group but not in the control group . The greatest score changes came from the physical appearance subscale . Participation in weight management programs may put children at risk for lower self-esteem ( self-concept ) while producing limited weight loss results OBJECTIVE This study examines the effect of an interactive , school-based , self-esteem education program on the body image and eating attitudes and behaviors of young male and female adolescents following the program and after 12 months . METHOD All 470 eligible students ( 63 % female ) aged 11 - 14 years volunteered to participate . The intervention group students participated in the program , whereas the control group students received their scheduled personal development and health class . RESULTS The program significantly improved the body satisfaction of the intervention students and significantly changed aspects of their self-esteem ; social acceptance , physical appearance , and athletic ability became less important for the intervention students and more important for control students . Female intervention students rated their physical appearance as perceived by others significantly higher than control students and allowed their body weight to increase appropriately by preventing the age increase in weight-losing behaviors of the control students . One year after the intervention , body image and attitude changes were still present . These findings also held for the 116 students ( 63 % females ) with low self-esteem and higher anxiety , who were considered at risk for the development of eating disorders . These students also had significantly lower drive for thinness and greater body satisfaction following the intervention and the decreased importance of physical appearance to their self-esteem was present at 12 months . Control at-risk students significantly decreased their body weight , whereas the weight of the intervention at-risk students significantly increased . The intervention program was effective , safe , having no effect on measures of students ' anxiety or depression , and was rated highly by students . DISCUSSION This is the first controlled educational intervention to successfully improve body image and to produce long-term changes in the attitudes and self-image of young adolescents . This new approach to prevent the development of eating disorders by improving self-esteem may be effective , particularly if reinforced by teachers and family Summary The purpose of this study was to investigate the effects of a cardiovascular fitness program on the self-concept and peer approval of seventh grade boys . Thirty-seven low self-esteem Ss were r and omly divided into a control group ( participated in no formal physical education activity ) and an experimental group ( participated in a special running training program ) . At the end of an 18 week training program the two groups were significantly different in cardiovascular endurance , indicating the efficacy of the experimental treatment . There was an increase in self-concept from pretest to posttest for the experimental group only . Neither group had a significant change in peer approval 36 boys and 36 girls in 4 fourth grade s were exposed to basketball movement conditions which included the skills of dribble , chest pass , lay-up , pivot , guarding , and two-h and set shot . Eight 1/2-hr . treatment periods were spread evenly over 4 wk . and took place within the regularly assigned school physical education period . Two class groups , which included 9 boys and 9 girls each , were r and omly assigned by class to an experimental group which received treatment while two class groups were assigned by class to the control group . No differences between changes in self-concept as estimated by the Piers-Harris scale for treatment and control conditions were significant Aerobic exercise has been associated with improvements in psychological status and physical fitness in adults , but its effects on children are less clear . The purpose of this study was to evaluate the effects of an aerobic exercise program on the self-concept , academic achievement , motor proficiency , and cardiovascular fitness of boys with learning disabilities . Fifty-four boys were r and omly assigned to one of two exercise programs lasting 20 weeks . One program emphasized aerobic exercise and the other consisted of similar but less vigorous activities . The self-concept , academic achievement , motor proficiency , and physical fitness of each subject was assessed before and after the exercise programs . The results from group comparisons demonstrated an association between the aerobic exercise program and improvement of self-concept and physical fitness . No effect on academic achievement or motor proficiency could be attributed to the aerobic exercise program . J Dev Behav Pediatr 8:274–277 , 1987 . Index terms : aerobic exercise , learning disabilities , sports , self-concept This study investigated a possible relationship between exercise intensity and mood alteration that commonly is associated with physical activity . 91 college students completed the Profile of Mood States before and after 20 min . of jogging at three intensities : 55 % , 75 % , and 79 % of age-adjusted maximum heart rate on different occasions . Exercisers also completed a demographic inventory , a Lie Scale , and the State-Trait Anxiety Inventory . Contrary to our expectations , the interaction between exercise intensity and pre-post mood benefits was not significant . Supporting the manipulation of exercise intensity , the univariate interaction between exercise intensity and pre-post exercise scores on Fatigue was significant . Joggers reported short-term mood benefits on the combined subscales of the Profile of Mood States , and each subscale contributed to the benefits . Thus , regardless of the low- or moderate-intensity , participants reported that they “ felt better ” after exercising The article examines whether participation in an aerobic exercise program ( AE ) , as compared with a traditional physical education class ( PE ) , significantly increased children 's perceived athletic competence , physical appearance , social acceptance , behavioral conduct , and global self-worth ; increased their figural creativity ; and improved aerobic power as measured by an 800-meter run around a track . Further research on the effects of different types of AE is discussed , as well as the need for aerobic conditioning in the elementary school This study investigated the relationship between improvement in Total Positive Self-concept scores and increase in sports skills before and after training of 10 weeks for 45 minutes daily by 12- to 14-yr.-old junior high school and 16- to 18-yr.-old senior high school boys and girls . The 288 subjects were selected using a stratified ( intact class ) r and om technique . Subjects were r and omly assigned to different sports , 96 to field-hockey and 96 to athletics ( 32 to discuss , 32 to long jump , and 32 to sprints ) . 96 control subjects were r and omly selected from one class of each age bracket . Analysis of covariance showed that the trained subjects scored significantly higher in total positive self . A positive correlation between gain in sports skill and increase in self-concept scores was noted for both boys and girls within each age group . Age and sex had no effect on this pattern . The result supports inclusion of success-oriented sports in the high school curriculum Aerobic exercise has been associated with improved psychological status and physical fitness in adults , but its effects in adolescents have been less clear . This study evaluated the effects of aerobic exercise on the self-concept , depression level , and physical fitness of juvenile delinquents . Ninety-eight incarcerated youths who volunteered to participate were assigned in a blind fashion to one of two exercise programs lasting three months . Sixty-nine completed all phases of the study and are the subjects of this report . One exercise program ( 32 subjects ) emphasized aerobic exercise ; the other ( 37 subjects ) , limited exertion . Before and after participating , each subject underwent measurement of self-concept , mood , and physical fitness . While the aerobic and comparison groups were initially similar , the data demonstrated an association between participation in the aerobic exercise program and improved self-concept , Output:	REVIEW ER 'S CONCLUSIONS The results indicate that exercise has positive short-term effects on self-esteem in children and young people . Since there are no known negative effects of exercise and many positive effects on physical health , exercise may be an important measure in improving children 's self-esteem .
MS21344	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Heart failure ( HF ) is an important cause of morbidity in patients with acute coronary syndromes ( ACS ) . C-reactive protein ( CRP ) has been implicated in experimental models as exacerbating myocardial injury , but data regarding the clinical relationship of high-sensitivity CRP ( hsCRP ) and B-type natriuretic peptide ( BNP ) concentrations with the risk of HF after ACS are few . METHODS PROVE IT-TIMI 22 r and omized 4162 patients who had been stabilized after ACS to either intensive or moderate statin therapy . hsCRP and BNP were measured 30 days after r and omization . Hospitalizations for HF and cardiovascular death occurring after day 30 were assessed for a mean follow-up of 24 months . RESULTS Patients who developed HF had higher concentrations of hsCRP ( 3.7 mg/L vs 1.9 mg/L , P < 0.001 ) and BNP ( 59 ng/L vs 22 ng/L , P < 0.0001 ) . HF increased in a stepwise manner with hsCRP quartile [ adjusted hazard ratio ( HR(adj ) ) for Q4 vs Q1 , 2.5 ; P = 0.01 ] and BNP quartile ( HR(adj ) for Q4 vs Q1 , 5.8 ; P < 0.001 ) , with similar results obtained for HF and cardiovascular death . In a multivariable analysis , higher concentrations of hsCRP and BNP were both independently associated with HF [ HR(adj ) , 1.9 for hsCRP > 2.0 mg/L ( P = 0.01 ) and 4.2 for BNP > 80 ng/L ( P < 0.001 ) ] . Patients with increases in both markers were at the greatest risk of HF , compared with patients without an increased marker concentration ( HR(adj ) , 8.3 ; P = 0.01 ) . The benefit of intensive statin therapy in reducing HF was consistent among all patients , regardless of hsCRP or BNP concentration . CONCLUSIONS Both hsCRP and BNP measured 30 days after ACS are independently associated with the risk of HF and cardiovascular death , with the greatest risk occurring when both markers are increased AIMS This study evaluated the predictive value of NT-proBNP for patients with diabetes mellitus and compared the prognostic aptitude of this neurohumoral marker to traditional markers of cardiovascular events . METHODS AND RESULTS A prospect i ve observational study was conducted in 631 diabetic patients . The composite endpoint consisted of unplanned hospitalization for cardiovascular events or death within the observation period of 12 months . Of all variables analysed ( age , gender , history of hypertension , ischaemic heart disease/any cardiac disease , smoking , duration of diabetes , body mass index , blood pressure , New York Heart Association-class , Dyspnoea score , Minnesota Living with Heart Failure Question naire , LDL-cholesterol , HbA(1c ) , creatinine , glomerular filtration rate ) , the logarithm of NT-proBNP gave the most potent information in a stepwise Cox regression analysis ( P < 0.0001 ) . Bootstrapping with 500 sample s supports this result in 95 % sample s. The negative predictive value of a normal value ( < 125 pg/mL ) of NT-proBNP for short-term cardiovascular events in diabetic patients is 98 % . CONCLUSION We have demonstrated a strong and independent correlation between NT-proBNP and short-term prognosis of cardiovascular events for patients with diabetes mellitus . With a high negative predictive value it can identify individuals who are not at intermediate risk for cardiovascular events . NT-proBNP proved to be of higher predictive value than traditional cardiovascular markers , in this unselected cohort CONTEXT Identification of individuals at high risk for cardiovascular events is important for the optimal use of primary and secondary prevention measures . OBJECTIVE To determine whether plasma levels of amino terminal fragment of the prohormone brain-type natriuretic peptide ( NT-proBNP ) predict cardiovascular events or death independent of other available prognostic tests . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study ( 2000 - 2002 ) of 987 individuals in California with stable coronary heart disease in the Heart and Soul Study , who were followed up for a mean of 3.7 ( range , 0.1 - 5.3 ) years . MAIN OUTCOME MEASURES The association of baseline NT-proBNP levels with death or cardiovascular events ( myocardial infa rct ion , stroke , or heart failure ) . Traditional clinical risk factors , echocardiographic measures , ischemia , other biomarkers , and New York Heart Association classification were adjusted for to determine whether NT-proBNP levels were independent of other prognostic factors . Receiver operating characteristic ( ROC ) curves were used to assess the incremental prognostic value of adding NT-proBNP level to these other measures . RESULTS A total of 256 participants ( 26.2 % ) had a cardiovascular event or died . Each increasing quartile of NT-proBNP level ( range of quartile 1 , 8.06 - 73.95 pg/mL ; quartile 2 , 74 - 174.5 pg/mL ; quartile 3 , 175.1 - 459 pg/mL ; quartile 4 , > or = 460 pg/mL ) was associated with a greater risk of cardiovascular events or death , ranging from 23 of 247 ( annual event rate , 2.6 % ) in the lowest quartile to 134 of 246 ( annual event rate , 19.6 % ) in the highest quartile ( unadjusted hazard ratio [ HR ] for quartile 4 vs quartile 1 , 7.8 ; 95 % confidence interval [ CI ] , 5.0 - 12.1 ; P<.001 ) . Each SD increase in log NT-proBNP level ( 1.3 pg/mL ) was associated with a 2.3-fold increased rate of adverse cardiovascular outcomes ( unadjusted HR , 2.3 ; 95 % CI , 2.0 - 2.6 ; P<.001 ) , and this association persisted after adjustment for all of the other prognostic measures ( adjusted HR , 1.7 ; 95 % CI , 1.3 - 2.2 ; P<.001 ) . The addition of NT-proBNP level to st and ard clinical assessment and complete echocardiographic parameters significantly improved the area under the ROC curves for predicting subsequent adverse cardiovascular outcomes ( 0.80 for clinical risk factors and echocardiographic parameters plus log NT-proBNP vs 0.76 for clinical risk factors and echocardiographic parameters only ; P = .006 ) . CONCLUSIONS Elevated levels of NT-proBNP predict cardiovascular morbidity and mortality , independent of other prognostic markers , and identify at-risk individuals even in the absence of systolic or diastolic dysfunction by echocardiography . Level of NT-proBNP may help guide risk stratification of high-risk individuals , such as those with coronary heart disease Aims /hypothesisRaised N-terminal pro-brain natriuretic peptide ( NT-proBNP ) is independently associated with an increased risk of death in chronic heart failure and acute coronary syndromes in nondiabetic population s. Diabetic nephropathy is characterised by an increased risk of cardiovascular morbidity and mortality . This study investigated the prognostic value of NT-proBNP in a large cohort of type 1 diabetic patients with and without diabetic nephropathy . Methods In a prospect i ve observational follow-up study , 198 type 1 diabetic patients with overt diabetic nephropathy ( 122 men , age [ mean±SD ] 41±10 years , duration of diabetes 28±8 years , GFR 74±33 ml min−1 ) and a matched control group of 188 patients with longst and ing type 1 diabetes and persistent normoalbuminuria ( 114 men , age 43±10 years , duration of diabetes 27±9 years ) were followed for 9.3 ( 0.0–9.5 ) years . Plasma NT-proBNP concentration was determined by immunoassay at baseline . Results In patients with diabetic nephropathy , plasma NT-proBNP concentration was elevated to ( median [ range ] ) 110 ( 5–79640 ) ng l−1 vs. 27 ( 5–455 ) ng l−1 in normoalbuminuric patients ( p<0.0001 ) . Among patients with nephropathy , 39 ( 39 % ) patients with plasma NT-proBNP concentrations above the median and 12 ( 12 % ) with values below the median died from any cause ( unadjusted hazard ratio 3.86 [ 95 % CI 2.02–7.37 ] , p<0.0001 ; covariate-adjusted hazard ratio 2.28 [ 1.04–4.99 ] , p=0.04 ) . This lower mortality rate was attributable to fewer cardiovascular deaths : 31 ( 31 % ) and 7 ( 7 % ) above and below the median NT-proBNP level respectively ( unadjusted hazard ratio 5.25 [ 2.31–11.92 ] , p<0.0001 ; covariate-adjusted hazard ratio 3.81 [ 1.46–9.94 ] , p=0.006 ) . Conclusions /interpretationElevated circulating NT-proBNP is a new independent predictor of the excess overall and cardiovascular mortality in diabetic nephropathy patients without symptoms of heart failure OBJECTIVES The purpose of this work was to assess the prognostic role of glomerular filtration rate ( GFR ) and NT-terminal pro-B-type natriuretic peptide ( NT-proBNP ) for mortality end points in the vascular population . BACKGROUND The GFR and NT-proBNP have been shown to predict mortality end points in free-living and limited vascular population s , independent of traditional risk factors . However , their prognostic power in an unrestricted vascular population is poorly understood . METHODS A total of 412 subjects from a vascular cohort with a history of either peripheral arterial disease ( PAD ) and /or other cardiovascular disease ( CVD ) were included in this prospect i ve cohort analysis and followed for an average of 6.7 years . Outcome variables were all-cause mortality , ischemic heart disease ( IHD ) mortality , and any cardiovascular mortality . The prognostic roles of GFR and NT-proBNP levels were determined using multivariate survival analysis . RESULTS Higher GFR ( per 10 ml/min/1.73 m2 ) was significantly protective for all-cause mortality ( hazard ratio [ HR ] 0.81 , p < 0.001 ) , IHD mortality ( HR 0.82 , p = 0.008 ) , and CVD mortality ( HR 0.84 , p = 0.005 ) . Conversely , NT-proBNP was not a significant predictor of any mortality end point . The GFR showed the strongest association in subjects with a history of other CVD . Although NT-proBNP did not demonstrate a significant prognostic role in any of the subgroups , the data were suggestive for patients with PAD alone . CONCLUSIONS Glomerular filtration rate was a robust predictor of all-cause , IHD , and cardiovascular mortality in the vascular population , particularly in those with a history of other CVD , while NT-proBNP showed a suggestive association limited to the group with PAD only . These findings suggest that these markers must be selectively applied in the vascular population for greatest clinical utility Objective : To evaluate N-terminal pro-brain natriuretic peptide ( NT-proBNP ) as a diagnostic and prognostic marker for systolic heart failure in the general population . Design : Study participants , r and omly selected to be representative of the background population , filled in a heart failure question naire and underwent pulse and blood pressure measurements , electrocardiography , echocardiography , and blood sampling and were followed up for a median ( range ) period of 805 ( 60−1171 ) days . Setting : Participants were recruited from four r and omly selected general practitioners and were examined in a Copenhagen university hospital . Patients : 382 women and 290 men in four age groups ( 50−59 ( n = 174 ) ; 60−69 ( n = 204 ) ; 70−79 ( n = 174 ) ; ⩾ 80 years ( n = 120 ) ) . Main outcome measures : Value of NT-proBNP in evaluating patients with symptoms of heart failure and impaired left ventricular ( LV ) systolic function ; prognostic value of NT-proBNP for mortality and hospital admissions . Results : In 38 ( 5.6 % ) participants LV ejection fraction ( LVEF ) was ⩽ 40 % . NT-proBNP identified patients Output:	Assay of BNP or NT-proBNP in addition to measurement of conventional CVD risk factors yielded generally modest improvements in risk discrimination . Available prospect i ve studies indicate strong associations between circulating concentration of natriuretic peptides and CVD risk under a range of different circumstances .
MS21345	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Few studies have analyzed intraclass differences in angiotensin II receptor blockers ( ARBs ) with respect to antidiabetic or metabolic effects . We design ed a prospect i ve r and omized study to compare a peroxisome proliferator-activated receptor-gamma (PPARgamma)-activating ARB with a nonactivating ARB to delineate the effects on metabolic factors associated with cardiovascular disease . Subjects initially comprised 153 hypertensive patients ( 72 men , 81 women ; mean age , 67.9 + /- 7.8 years ) with diagnosed glucose intolerance on the glucose loading test . Patients were r and omly assigned to receive 6-month administration of telmisartan 47.0 mg/d ( TEL ) or c and esartan 8.4 mg/d ( CAN ) , or to have no change in drug regimen ( control group , CTL ) . Fasting plasma glucose level was significantly reduced in TEL ( n = 46 ) compared with CTL ( n = 47 ) ( percentage of change from baseline , -1.7 % vs + 2.2 % ; P = .045 ) . Percentage of increase in adiponectin was significantly larger in TEL than in CTL ( + 10.5 % vs + 2.2 % , P = .025 ) , but not significantly larger in CAN ( n = 44 ) than in CTL ( + 4.9 % vs + 2.2 % ; P = .13 ) . Percentage of decrease in body weight from baseline was significantly enhanced in TEL compared with CTL ( -2.2 % vs -0.8 % , P = .023 ) and CAN ( -2.2 % vs -0.3 % , P = .007 ) . Telmisartan decreased body weight while increasing serum adiponectin levels in hypertensive patients with glucose intolerance . C and esartan did not achieve similar improvements in these patients . Among ARBs , telmisartan may have a larger impact on obesity-related diseases that can lead to cardiovascular disorders Aim . This study compared the effects of telmisartan and losartan on nonalcoholic fatty liver disease ( NAFLD ) and biochemical markers of insulin resistance in hypertensive NAFLD patients with type 2 diabetes mellitus . Methods . This was a r and omized , open-label , parallel-group comparison of therapy with telmisartan or losartan . Nineteen hypertensive NAFLD patients with type 2 diabetes were r and omly assigned to receive telmisartan at a dose of 20 mg once a day ( n = 12 ) or losartan at a dose of 50 mg once a day ( n = 7 ) for 12 months . Body fat area as determined by CT scanning and hepatic fat content based on the liver-to-spleen ( L/S ) ratio , as well as several parameters of glycemic and lipid metabolism , were compared before and after 12 months . Results . The telmisartan group showed a significant decline in serum free fatty acid ( FFA ) level ( from 0.87 ± 0.26 to 0.59 ± 0.22 mEq/L ( mean ± SD ) , P = 0.005 ) and a significant increase in L/S ratio ( P = 0.049 ) evaluated by CT scan , while these parameters were not changed in the losartan group . Conclusion . Although there was no significant difference in improvement in liver enzymes with telmisartan and losartan treatment in hypertensive NAFLD patients with type 2 diabetes after 12 months , it is suggested that telmisartan may exert beneficial effects by improving fatty liver To examine the effects of telmisartan on peroxisome proliferator – activated receptor γ activation , we compared the effects of telmisartan with those of c and esartan on adipocytokines and glucose and lipid metabolism in vivo and in vitro . In vivo , 56 patients with both type 2 diabetes and hypertension were enrolled and r and omized to receive either telmisartan ( 40 mg ) or c and esartan ( 8 mg ) for 3 months . Serum adiponectin , HbA1c levels , lipid profiles and blood pressure were recorded at the beginning and 3 months later . In vitro , differentiated 3T3-L1 adipocytes were treated with telmisartan , c and esartan , pioglitazone or vehicle for 24 h , and then adiponectin mRNA and protein levels were measured . The results showed that most of the metabolic parameters , including the lipid profiles , did not change significantly during the study in either group . However , the changes in serum adiponectin and plasma glucose over 3 months were significantly greater in the telmisartan group than in the c and esartan group . In vitro , although the protein level of adiponectin was not significantly elevated , the mRNA expression of adiponectin was elevated 1.5-fold by telmisartan in 3T3-L1 adipocytes . Our findings suggest that telmisartan may have beneficial effects in type 2 diabetes beyond its antihypertensive effect OBJECTIVE PPARgamma agonists are widely used in type 2 diabetic patients to reduce insulin resistance . Recently , telmisartan , an AT1 receptor antagonist , was reported to function as a partial agonist of PPARgamma based on in vitro experiments . The aim of the present study was to investigate whether the PPARgamma enhancing activity of telmisartan is exerted clinical ly in diabetic patients . METHODS We compared the effects of telmisartan with those of c and esartan , on insulin sensitivity , the serum levels of various adipocytokines and oxidative stress . PATIENTS In total , 85 Japanese type 2 diabetic patients with hypertension , maintained on 8 mg per day of c and esartan , were r and omly assigned to the TM group ( c and esartan switched to 40 mg of telmisartan , n=38 ) or the CD group ( no treatment change , n=47 ) . RESULTS After 3 months , oxidized lipids were significantly decreased only in the TM group . Although the homeostasis assessment model of insulin resistance ( HOMA-R ) tended to be improved and serum concentrations of HDL-cholesterol and HMW adiponectin tended to be increased only in the TM group , these alterations were too small to be significant by unpaired t-test . Interestingly , in subgroup analysis , the alterations of HOMA-R , serum concentrations of oxidized lipids , and HMW adiponectin were more apparent in obese TM group subjects and the changes reached statistical significance . CONCLUSION Switching from c and esartan to telmisartan in obese subjects increases serum adiponectin and improves both insulin resistance and oxidative stress , while these effects were not statistically apparent in the total patient population . These results support the idea that telmisartan exerts its PPARgamma enhancing activity clinical ly in obese type 2 diabetic patients Background : There is increasing evidence that inhibition of the renin-angiotensin system provides renoprotection independent of blood pressure lowering . The aim of the present study was to determine whether various angiotensin II receptor blockers ( ARBs ) affect urinary albumin excretion ( UAE ) , urinary liver-type fatty acid-binding protein ( L-FABP ) and 8-hydroxy-2′-deoxyguanosine ( 8-OHdG ) levels in early-stage diabetic nephropathy patients with microalbuminuria . Methods : Sixty-eight diabetic nephropathy patients with microalbuminuria were r and omly allocated to 1 of 4 treatment groups : losartan 100 mg/day ( group A ) , c and esartan 12 mg/day ( group B ) , olmesartan 40 mg/day ( group C ) , or telmisartan 80 mg/day ( group D ) . Treatment was continued for 12 months . UAE , L-FABP and 8-OHdG excretion , serum creatinine , and 24-hour creatinine clearance ( Ccr ) were measured . Results : The serum creatinine and 24-hour Ccr were not affected during the experimental period in any of the groups . Systolic and diastolic blood pressures , UAE , urinary L-FABP and 8-OHdG excretion were significantly reduced after 6 and 12 months compared with baseline in any of the groups . ΔL-FABP and Δ8-OHdG were significantly greater in group D than in the other 3 groups after 12 months . Conclusions : ARBs have renoprotection and this effect of telmisartan appears to be more potent than that of losartan , c and esartan , or olmesartan in early-stage diabetic nephropathy patients AIM To evaluate insulin resistance , cytolysis and non-alcoholic steatohepatitis ( NASH ) score ( NAS ) using the Kleiner and Brunt criteria in 54 patients with NASH and mild-to-moderate hypertension , treated with telmisartan vs valsartan for 20 mo . METHODS All patients met the NCEP-ATP III criteria for metabolic syndrome . Histology confirmed steatohepatitis , defined as a NAS greater than five up to 3 wk prior inclusion , using the current criteria . Patients with viral hepatitis , chronic alcohol intake , drug abuse or other significant immune or metabolic hepatic pathology were excluded . Subjects were r and omly assigned either to the valsartan ( V ) group ( st and ard dose 80 mg o.d . , n = 26 ) , or to the telmisartan ( T ) group ( st and ard dose 20 mg o.d . , n = 28 ) . Treatment had to be taken daily at the same hour with no concomitant medication or alcohol consumption allowed . Neither the patient nor the medical staff was aware of treatment group allocation . Paired liver biopsies obtained at inclusion ( visit 1 ) and end of treatment ( EOT ) were assessed by a single blinded pathologist , not aware of patient or treatment group . Blood pressure , BMI , ALT , AST , HOMA-IR , plasma triglycerides ( TG ) and total cholesterol ( TC ) were evaluated at inclusion and every 4 mo until EOT ( visit 6 ) . RESULTS At EOT we noticed a significant decrease in ALT levels vs inclusion in all patients and this decrease did not differ significantly in group T vs group V. HOMA-IR significantly decreased at EOT vs inclusion in all patients but in group T , the mean HOMA-IR decrease per month was higher than in group V. NAS significantly diminished at EOT in all patients with a higher decrease in group T vs group V. CONCLUSION Angiotensin receptor blockers seem to be efficient in hypertension-associated NASH . Telmisartan showed a higher efficacy regarding insulin resistance and histology , perhaps because of its specific PPAR-gamma lig and effect OBJECTIVE To investigate the effects of telmisartan on body fat distribution and insulin sensitivity in patients with hypertension and obesity . METHODS In this prospect i ve , r and omized study , out patients from the Sixth People 's Hospital affiliated to Shanghai Jiaotong University , Shanghai , China were treated with telmisartan ( n=23 ) , or losartan ( n=22 ) for 16 weeks between December 2009 to January 2011 . Parameters such as waist and hip circumference , body mass index , fasting blood glucose , insulin , lipids , serum adiponectin , and tumor necrosis factor-alpha ( TNF-alpha ) were measured before and after treatment . The abdominal visceral fat area ( VFA ) and subcutaneous fat area ( SFA ) were determined by magnetic resonance imaging . Insulin sensitivity was estimated by homeostasis model assessment ( HOMA-IR ) . RESULTS Compared with baseline , the systolic and diastolic blood pressure decreased significantly in both groups . However , the levels of HOMA-IR , serum adiponectin , and TNF-alpha only improved in the telmisartan group . Similarly , the VFA was reduced in the telmisartan group , while the SFA did not change in either group . CONCLUSION Telmisartan improves both hemodynamic and metabolic abnormalities found in hypertensive patients with obesity . The additional benefits may be partly due to visceral fat remodeling Introduction The number of patients with both hypertension and obesity has been increasing in Japan . Many of these patients may also have insulin resistance . Telmisartan , an angiotensin II receptor blocker ( ARB ) , selectively activates peroxisome proliferatoractivated receptor (PPAR)-gamma , and this effect is considered to markedly improve insulin resistance in obese patients with hypertension . We compared the antihypertensive and insulin resistance-improving effects of telmisartan with those of c and esartan and valsartan in this patient population . Methods Twenty-eight elderly patients with an average body mass index ( BMI ) of 27.1 kg/m2 were enrolled in this 6-month study . Patients were r and omly selected to either switch from c and esartan or valsartan to telmisartan or to continue with their current ARB . A 75 g oral glucose tolerance test ( OGTT ) was performed before and after switching , and the effect of telmisartan on the insulin response to glucose loading was investigated . Results There was no significant difference in blood pressure between the two groups after drug administration , but glucose tolerance significantly improved in the telmisartan group . The hyperinsulin response to glucose loading also significantly improved in those taking telmisartan , as well as homeostasis model assessment of insulin resistance ( HOMA Output:	Conclusion : Telmisartan can better improve IR compared with other ARBs
MS21346	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Studies of the use of anti-inflammatory asthma therapy have been limited to selected population s or have been unable to assess the appropriateness of therapy for individuals . OBJECTIVE We sought to describe the current use of asthma medication in the United States population and to examine the influence of symptoms and sociodemographics on medication use . METHODS This study was based on a cross-sectional , national , r and om-digit-dial household telephone survey in 1998 design ed to identify adult patients and parents of children with current asthma . Respondents were classified as having current asthma if they had a physician 's diagnosis of asthma and were either taking medication for asthma or had asthma symptoms during the past year . RESULTS One or more persons met the study criteria for current asthma in 3273 ( 7.8 % ) households in which a screening question naire was completed . Of these , 2509 persons ( 721 children < 16 years ) with current asthma were interviewed . Current use of anti-inflammatory medication was reported by 507 ( 20.1 % ) . Of these , most were using inhaled corticosteroids ( 72.5 % ) , with use of antileukotrienes reported by 11.4 % and use of cromolyn-nedocromil reported by 18.6 % . Of persons with persistent asthma symptoms in the past month , 26.2 % reported current use of some form of anti-inflammatory medication . In bivariate analysis persons reporting lower income , less education , and present unemployment , as well as smokers , were significantly ( P < .001 ) less likely to report current anti-inflammatory use than were other population s. In a multiple regression model nonsmokers and those of white , non-Hispanic ethnicity , as well as persons reporting less asthma control , were more likely to report current anti-inflammatory medication use . CONCLUSION In the United States use of appropriate asthma therapy remains inadequate . Strategies to increase use of anti-inflammatory therapy among patients with asthma are needed . These might include methods to increase access to asthma care for minorities and the socioeconomically disadvantaged Background In patients with prednisone-dependent asthma the dose of oral corticosteroids should be adjusted to the lowest possible level to reduce long-term adverse effects . However , the optimal strategy for tapering oral corticosteroids is unknown . Objective To investigate whether an internet-based management tool including home monitoring of symptoms , lung function and fraction of exhaled nitric oxide ( FENO ) facilitates tapering of oral corticosteroids and leads to reduction of corticosteroid consumption without worsening asthma control or asthma-related quality of life . Methods In a 6-month pragmatic r and omised prospect i ve multicentre study , 95 adults with prednisone-dependent asthma from six pulmonary outpatient clinics were allocated to two tapering strategies : according to conventional treatment ( n=43 ) or guided by a novel internet-based monitoring system ( internet strategy ) ( n=52 ) . Primary outcomes were cumulative sparing of prednisone , asthma control and asthma-related quality of life . Secondary outcomes were forced expiratory volume in 1 s ( FEV1 ) , exacerbations , hospitalisations and patient 's satisfaction with the tapering strategy . Results Median cumulative sparing of prednisone was 205 ( 25–75th percentile −221 to 777 ) mg in the internet strategy group compared with 0 ( −497 to 282 ) mg in the conventional treatment group ( p=0.02 ) . Changes in prednisone dose ( mixed effect regression model ) from baseline were −4.79 mg/day and + 1.59 mg/day , respectively ( p<0.001 ) . Asthma control , asthma-related quality of life , FEV1 , exacerbations , hospitalisations and satisfaction with the strategy were not different between groups . Conclusions An internet-based management tool including home monitoring of symptoms , lung function and FENO in severe asthma is superior to conventional treatment in reducing total corticosteroid consumption without compromising asthma control or asthma-related quality of life . Clinical trial registration number Clinical trial registered with http://www.trialregister.nl ( Netherl and s Trial Register number 1146 ) Background Internet-based self-management has shown to improve asthma control and asthma related quality of life , but the improvements were only marginally clinical ly relevant for the group as a whole . We hypothesized that self-management guided by weekly monitoring of asthma control tailors pharmacological therapy to individual needs and improves asthma control for patients with partly controlled or uncontrolled asthma . Methods In a 1-year r and omised controlled trial involving 200 adults ( 18 - 50 years ) with mild to moderate persistent asthma we evaluated the adherence with weekly monitoring and effect on asthma control and pharmacological treatment of a self-management algorithm based on the Asthma Control Question naire ( ACQ ) . Participants were assigned either to the Internet group ( n = 101 ) that monitored asthma control weekly with the ACQ on the Internet and adjusted treatment using a self-management algorithm supervised by an asthma nurse specialist or to the usual care group ( UC ) ( n = 99 ) . We analysed 3 subgroups : patients with well controlled ( ACQ ≤ 0.75 ) , partly controlled ( 0.75>ACQ ≤ 1.5 ) or uncontrolled ( ACQ>1.5 ) asthma at baseline . Results Overall monitoring adherence was 67 % ( 95 % CI , 60 % to 74 % ) . Improvements in ACQ score after 12 months were -0.14 ( p = 0.23 ) , -0.52 ( p < 0.001 ) and -0.82 ( p < 0.001 ) in the Internet group compared to usual care for patients with well , partly and uncontrolled asthma at baseline , respectively . Daily inhaled corticosteroid dose significantly increased in the Internet group compared to usual care in the first 3 months in patients with uncontrolled asthma ( + 278 μg , p = 0.001 ) , but not in patients with well or partly controlled asthma . After one year there were no differences in daily inhaled corticosteroid use or long-acting β2-agonists between the Internet group and usual care . Conclusions Weekly self-monitoring and subsequent treatment adjustment leads to improved asthma control in patients with partly and uncontrolled asthma at baseline and tailors asthma medication to individual patients ' needs . Trial registration Current Controlled Trials IS RCT OBJECTIVE : Asthma continues to be 1 of the most common chronic diseases of childhood and affects ∼6 million US children . Although National Asthma Education Prevention Program guidelines exist and are widely accepted , previous studies have demonstrated poor clinician adherence across a variety of population s. We sought to determine if clinical decision support ( CDS ) embedded in an electronic health record ( EHR ) would improve clinician adherence to national asthma guidelines in the primary care setting . METHODS : We conducted a prospect i ve cluster-r and omized trial in 12 primary care sites over a 1-year period . Practice s were stratified for analysis according to whether the site was urban or suburban . Children aged 0 to 18 years with persistent asthma were identified by International Classification of Diseases , Ninth Revision codes for asthma . The 6 intervention- practice sites had CDS alerts imbedded in the EHR . Outcomes of interest were the proportion of children with at least 1 prescription for controller medication , an up-to- date asthma care plan , and the performance of office-based spirometry . RESULTS : Increases in the number of prescriptions for controller medications , over time , was 6 % greater ( P = .006 ) and 3 % greater for spirometry ( P = .04 ) in the intervention urban practice s. Filing an up-to- date asthma care plan improved 14 % ( P = .03 ) and spirometry improved 6 % ( P = .003 ) in the suburban practice s with the intervention . CONCLUSION : In our study , using a cluster-r and omized trial design , CDS in the EHR , at the point of care , improved clinician compliance with National Asthma Education Prevention Program guidelines BACKGROUND Although computerized physician order entry reduces medication errors among in patients , little is known about the use of this system in primary care . METHODS We calculated the override rate among 3481 consecutive alerts generated at 5 adult primary care practice s that use a common computerized physician order entry system for prescription writing . For detailed review , we selected a r and om sample of 67 alerts in which physicians did not prescribe an alerted medication and 122 alerts that result ed in a written prescription . We identified factors associated with the physicians ' decisions to override a medication alert , and determined whether an adverse drug event ( ADE ) occurred . RESULTS Physicians overrode 91.2 % of drug allergy and 89.4 % of high-severity drug interaction alerts . In the multivariable analysis using the medical chart review sample ( n = 189 ) , physicians were less likely to prescribe an alerted medication if the prescriber was a house officer ( odds ratio [ OR ] , 0.26 ; 95 % confidence interval [ CI ] , 0.08 - 0.84 ) and if the patient had many drug allergies ( OR , 0.70 ; 95 % CI , 0.53 - 0.93 ) . They were more likely to override alerts for renewals compared with new prescriptions ( OR , 17.74 ; 95 % CI , 5.60 - 56.18 ) . We found no ADEs in cases where physicians observed the alert and 3 ADEs among patients with alert overrides , a nonsignificant difference ( P = .55 ) . Physician review ers judged that 36.5 % of the alerts were inappropriate . CONCLUSIONS Few physicians changed their prescription in response to a drug allergy or interaction alert , and there were few ADEs , suggesting that the threshold for alerting was set too low . Computerized physician order entry systems should suppress alerts for renewals of medication combinations that patients currently tolerate Purpose : Physicians and patients frequently miss opportunities to improve the quality of care of diabetes , primarily because of the complexity of managing many risk factors over many years with many other providers . Electronic decision support is a potential way to improve prescribing and quality of care . Shared care , meaning patients and physicians sharing access to the patient ’s status compared to recommended targets , is thought to improve outcomes as are supportive reminders . Our objective was to rigorously evaluate whether an electronic medical record (EMR)-linked , individualized electronic diabetes tracker with automated telephone reminders could improve the quality of diabetes management in primary care . Methods : Community-based family physicians across Ontario who were already using EMRs in their practice , were recruited . Patient and physician versions of a Web-based diabetes tracker , the ( COMPETE II Diabetes Tracker ( CIIDT ) system , were developed . The main tracker page showed all 13 monitoring variables – the patient ’s recent values , both process ( when last checked ) and outcome ( the result ) , target values for process and outcome , and short advisory messages , with red/yellow/green highlighting to indicate urgency of review . Links to best evidence guidelines and patient re sources were provided . The physician view appeared as an overlay in a corner of their own electronic medical record ( N = 6 EMR products ) . Intervention patients were linked to a voice biometric-enabled automated telephone reminder system ( ATRS ) for medications , labs and visits . Consenting patients with diabetes were r and omized to the CIIDT-ATRS intervention or usual care ( neither ) . Since the study was relatively short ( 6 months follow-up ) , the primary outcome was a composite score of process quality – the quality of monitoring the variables compared to target . Secondary outcomes included clinical outcomes plus evaluations of the tracker and ATRS , and impact on health information privacy . Results : Forty-eight physicians ( mean age ( SD ) = 45.2 ( 10.0 ) , 38.2 % female ) were recruited and 511 patients ( mean age ( SD ) = 60.3 ( 12.4 ) , 49.6 % female , 78 % completed high school ) were r and omized . Only 46.1 % of patients used the Internet at least monthly so print versions of their recent information were sent to them prior to their physician visits . There were frequent technical problems with the Web-based tracker and a lack of data integration between the various EMRs and the tracker . Despite problems , the primary outcome of composite score of physician visits , and checks of blood pressure ( BP ) , LDL cholesterol , HbA1C , microalbuminuria , BMI , feet and eyes , showed a highly statistically significant improvement in the intervention group compared to control ( p<0.0001 ) . There were also highly statistically significant improvements in actual blood pressure ( -2.68 mm diastolic BP , p=0.007 ) and in HbA1C ( -.2 % , p=0.001 ) . 75.9 % of intervention patients were as satisfied or more satisfied with their care since the use of the tracker system and 62.5 % voted to continue to receive ATRS reminders . 22.4 % of patients felt that , in general , the risk of possible loss of confidentiality outweighed the benefits that computers could bring to their health . Over the course of the study , physicians developed a more favourable attitude towards the benefits vs risks of computerized systems in healthcare . Discussion : Despite considerable technical challenges for both patients and physicians , we have demonstrated that the care of a complex chronic disease can be improved with electronic tracking and decision support for both physician and patient . Output:	Conclusion Evidence supports the effectiveness of CCDSS in the care of people with asthma . However there is very little information of its use in COPD care . Although there is considerable improvement in the health care process measures and clinical outcomes through the use of CCDSSs , its effects on user workload and efficiency , safety , costs of care , provider and patient satisfaction remain understudied
MS21347	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Treatment of glioblastoma ( GBM ) , the most common primary malignant brain tumor in adults , remains a significant unmet need in oncology . Historically , cytotoxic treatments provided little durable benefit , and tumors recurred within several months . This has spurred a substantial research effort to establish more effective therapies for both newly diagnosed and recurrent GBM . In this context , antiangiogenic therapy emerged as a promising treatment strategy because GBMs are highly vascular tumors . In particular , GBMs overexpress vascular endothelial growth factor ( VEGF ) , a proangiogenic cytokine . Indeed , many studies have demonstrated promising radiographic response rates , delayed tumor progression , and a relatively safe profile for anti-VEGF agents . However , r and omized phase III trials conducted to date have failed to show an overall survival benefit for antiangiogenic agents alone or in combination with chemoradiotherapy . These results indicate that antiangiogenic agents may not be beneficial in unselected population s of patients with GBM . Unfortunately , biomarker development has lagged behind in the process of drug development , and no vali date d biomarker exists for patient stratification . However , hypothesis-generating data from phase II trials that reveal an association between increased perfusion and /or oxygenation ( ie , consequences of vascular normalization ) and survival suggest that early imaging biomarkers could help identify the subset of patients who most likely will benefit from anti-VEGF agents . In this article , we discuss the lessons learned from the trials conducted to date and how we could potentially use recent advances in GBM biology and imaging to improve outcomes of patients with GBM who receive antiangiogenic therapy BACKGROUND Treatment options for recurrent glioblastoma are scarce , with second-line chemotherapy showing only modest activity against the tumour . Despite the absence of well controlled trials , bevacizumab is widely used in the treatment of recurrent glioblastoma . Nonetheless , whether the high response rates reported after treatment with this drug translate into an overall survival benefit remains unclear . We report the results of the first r and omised controlled phase 2 trial of bevacizumab in recurrent glioblastoma . METHODS The BELOB trial was an open-label , three-group , multicentre phase 2 study undertaken in 14 hospitals in the Netherl and s. Adult patients ( ≥18 years of age ) with a first recurrence of a glioblastoma after temozolomide chemoradiotherapy were r and omly allocated by a web-based program to treatment with oral lomustine 110 mg/m(2 ) once every 6 weeks , intravenous bevacizumab 10 mg/kg once every 2 weeks , or combination treatment with lomustine 110 mg/m(2 ) every 6 weeks and bevacizumab 10 mg/kg every 2 weeks . R and omisation of patients was stratified with a minimisation procedure , in which the stratification factors were centre , Eastern Cooperative Oncology Group performance status , and age . The primary outcome was overall survival at 9 months , analysed by intention to treat . A safety analysis was planned after the first ten patients completed two cycles of 6 weeks in the combination treatment group . This trial is registered with the Nederl and s Trial Register ( www.trialregister.nl , number NTR1929 ) . FINDINGS Between Dec 11 , 2009 , and Nov 10 , 2011 , 153 patients were enrolled . The preplanned safety analysis was done after eight patients had been treated , because of haematological adverse events ( three patients had grade 3 thrombocytopenia and two had grade 4 thrombocytopenia ) which reduced bevacizumab dose intensity ; the lomustine dose in the combination treatment group was thereafter reduced to 90 mg/m(2 ) . Thus , in addition to the eight patients who were r and omly assigned to receive bevacizumab plus lomustine 110 mg/m(2 ) , 51 patients were assigned to receive bevacizumab alone , 47 to receive lomustine alone , and 47 to receive bevacizumab plus lomustine 90 mg/m(2 ) . Of these patients , 50 in the bevacizumab alone group , 46 in the lomustine alone group , and 44 in the bevacizumab and lomustine 90 mg/m(2 ) group were eligible for analyses . 9-month overall survival was 43 % ( 95 % CI 29 - 57 ) in the lomustine group , 38 % ( 25 - 51 ) in the bevacizumab group , 59 % ( 43 - 72 ) in the bevacizumab and lomustine 90 mg/m(2 ) group , 87 % ( 39 - 98 ) in the bevacizumab and lomustine 110 mg/m(2 ) group , and 63 % ( 49 - 75 ) for the combined bevacizumab and lomustine groups . After the reduction in lomustine dose in the combination group , the combined treatment was well tolerated . The most frequent grade 3 or worse toxicities were hypertension ( 13 [ 26 % ] of 50 patients in the bevacizumab group , three [ 7 % ] of 46 in the lomustine group , and 11 [ 25 % ] of 44 in the bevacizumab and lomustine 90 mg/m(2 ) group ) , fatigue ( two [ 4 % ] , four [ 9 % ] , and eight [ 18 % ] ) , and infections ( three [ 6 % ] , two [ 4 % ] , and five [ 11 % ] ) . At the time of this analysis , 144/148 ( 97 % ) of patients had died and three ( 2 % ) were still on treatment . INTERPRETATION The combination of bevacizumab and lomustine met prespecified criteria for assessment of this treatment in further phase 3 studies . However , the results in the bevacizumab alone group do not justify further studies of this treatment . FUNDING Roche Nederl and and KWF Kankerbestrijding Significance This study demonstrates that antiangiogenic therapy increases tumor blood perfusion in a subset of newly diagnosed glioblastoma patients , and that it is these patients who survive longer when this expensive and potentially toxic therapy is combined with st and ard radiation and chemotherapy . This study provides fresh insights into the selection of glioblastoma patients most likely to benefit from antiangiogenic treatments . Antiangiogenic therapy has shown clear activity and improved survival benefit for certain tumor types . However , an incomplete underst and ing of the mechanisms of action of antiangiogenic agents has hindered optimization and broader application of this new therapeutic modality . In particular , the impact of antiangiogenic therapy on tumor blood flow and oxygenation status ( i.e. , the role of vessel pruning versus normalization ) remains controversial . This controversy has become critical as multiple phase III trials of anti-VEGF agents combined with cytotoxics failed to show overall survival benefit in newly diagnosed glioblastoma ( nGBM ) patients and several other cancers . Here , we shed light on mechanisms of nGBM response to cediranib , a pan-VEGF receptor tyrosine kinase inhibitor , using MRI techniques and blood biomarkers in prospect i ve phase II clinical trials of cediranib with chemoradiation vs. chemoradiation alone in nGBM patients . We demonstrate that improved perfusion occurs only in a subset of patients in cediranib-containing regimens , and is associated with improved overall survival in these nGBM patients . Moreover , an increase in perfusion is associated with improved tumor oxygenation status as well as with pharmacodynamic biomarkers , such as changes in plasma placenta growth factor and sVEGFR2 . Finally , treatment resistance was associated with elevated plasma IL-8 and sVEGFR1 posttherapy . In conclusion , tumor perfusion changes after antiangiogenic therapy may distinguish responders vs. nonresponders early in the course of this expensive and potentially toxic form of therapy , and these results may provide new insight into the selection of glioblastoma patients most likely to benefit from anti-VEGF treatments BACKGROUND Survival outcomes for patients with glioblastoma remain poor , particularly for patients with unmethylated O(6)-methylguanine-DNA methyltransferase ( MGMT ) gene promoter . This phase II , r and omized , open-label , multicenter trial investigated the efficacy and safety of 2 dose regimens of the selective integrin inhibitor cilengitide combined with st and ard chemoradiotherapy in patients with newly diagnosed glioblastoma and an unmethylated MGMT promoter . METHODS Overall , 265 patients were r and omized ( 1:1:1 ) to st and ard cilengitide ( 2000 mg 2 × /wk ; n = 88 ) , intensive cilengitide ( 2000 mg 5 × /wk during wk 1 - 6 , thereafter 2 × /wk ; n = 88 ) , or a control arm ( chemoradiotherapy alone ; n = 89 ) . Cilengitide was administered intravenously in combination with daily temozolomide ( TMZ ) and concomitant radiotherapy ( RT ; wk 1 - 6 ) , followed by TMZ maintenance therapy ( TMZ/RT→TMZ ) . The primary endpoint was overall survival ; secondary endpoints included progression-free survival , pharmacokinetics , and safety and tolerability . RESULTS Median overall survival was 16.3 months in the st and ard cilengitide arm ( hazard ratio [ HR ] , 0.686 ; 95 % CI : 0.484 , 0.972 ; P = .032 ) and 14.5 months in the intensive cilengitide arm ( HR , 0.858 ; 95 % CI : 0.612 , 1.204 ; P = .3771 ) versus 13.4 months in the control arm . Median progression-free survival assessed per independent review committee was 5.6 months ( HR , 0.822 ; 95 % CI : 0.595 , 1.134 ) and 5.9 months ( HR , 0.794 ; 95 % CI : 0.575 , 1.096 ) in the st and ard and intensive cilengitide arms , respectively , versus 4.1 months in the control arm . Cilengitide was well tolerated . CONCLUSIONS St and ard and intensive cilengitide dose regimens were well tolerated in combination with TMZ/RT→TMZ . Inconsistent overall survival and progression-free survival outcomes and a limited sample size did not allow firm conclusions regarding clinical efficacy in this exploratory phase II study PURPOSE This phase III open-label study compared the efficacy and safety of enzastaurin versus lomustine in patients with recurrent glioblastoma ( WHO grade 4 ) . PATIENTS AND METHODS Patients were r and omly assigned 2:1 to receive 6-week cycles of enzastaurin 500 mg/d ( 1,125-mg loading dose , day 1 ) or lomustine ( 100 to 130 mg/m(2 ) , day 1 ) . Assuming a 45 % improvement in progression-free survival ( PFS ) , 397 patients were required to provide 80 % power to achieve statistical significance at a one-sided level of .025 . RESULTS Enrollment was terminated at 266 patients ( enzastaurin , n = 174 ; lomustine , n = 92 ) after a planned interim analysis for futility . Patient characteristics were balanced between arms . Median PFS ( 1.5 v 1.6 months ; hazard ratio [ HR ] = 1.28 ; 95 % CI , 0.97 to 1.70 ) , overall survival ( 6.6 v 7.1 months ; HR = 1.20 ; 95 % CI , 0.88 to 1.65 ) , and 6-month PFS rate ( P = .13 ) did not differ significantly between enzastaurin and lomustine , respectively . Stable disease occurred in 38.5 % and 35.9 % of patients and objective response occurred in 2.9 % and 4.3 % of patients , respectively . Time to deterioration of physical and functional well-being and symptoms did not differ between arms ( HR = 1.12 ; P = .54 ) . Four patients discontinued enzastaurin because of drug-related serious adverse events ( AEs ) . Eleven patients treated with enzastaurin died on study ( four because of AEs ; one was drug-related ) . All four deaths that occurred in patients receiving lomustine were disease-related . Grade 3 to 4 hematologic toxicities were significantly higher with lomustine ( 46 events ) than with enzastaurin ( one event ; P < or = .001 ) . CONCLUSION Enzastaurin was well tolerated and had a better hematologic toxicity profile but did not have superior efficacy compared with lomustine in patients with recurrent glioblastoma PURPOSE To evaluate single-agent activity of bevacizumab in patients with recurrent glioblastoma . PATIENTS AND METHODS Patients with recurrent glioblastoma were treated with bevacizumab 10 mg/kg every 2 weeks . After tumor progression , patients were immediately treated with bevacizumab in combination with irinotecan 340 mg/m Output:	antiangiogenic drugs did not improve overall survival in glioblastoma patients , either as first or second-line treatment , and either as single agent or in combination with chemotherapy . Among antiangiogenic drugs , only bevacizumab improved progression-free survival regardless of treatment line , both as single agent or in combination with chemotherapy
MS21348	*TASK* the task is to summarize an input biomedical literature in six sentences *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 recent recognition that coronary-artery stenting has improved the short- and long-term outcomes of patients treated with angioplasty has made it necessary to reevaluate the relative benefits of bypass surgery and percutaneous interventions in patients with multivessel disease . METHODS A total of 1205 patients were r and omly assigned to undergo stent implantation or bypass surgery when a cardiac surgeon and an interventional cardiologist agreed that the same extent of revascularization could be achieved by either technique . The primary clinical end point was freedom from major adverse cardiac and cerebrovascular events at one year . The costs of hospital re sources used were also determined . RESULTS At one year , there was no significant difference between the two groups in terms of the rates of death , stroke , or myocardial infa rct ion . Among patients who survived without a stroke or a myocardial infa rct ion , 16.8 percent of those in the stenting group underwent a second revascularization , as compared with 3.5 percent of those in the surgery group . The rate of event-free survival at one year was 73.8 percent among the patients who received stents and 87.8 percent among those who underwent bypass surgery ( P<0.001 by the log-rank test ) . The costs for the initial procedure were $ 4,212 less for patients assigned to stenting than for those assigned to bypass surgery , but this difference was reduced during follow-up because of the increased need for repeated revascularization ; after one year , the net difference in favor of stenting was estimated to be $ 2,973 per patient . CONCLUSION As measured one year after the procedure , coronary stenting for multivessel disease is less expensive than bypass surgery and offers the same degree of protection against death , stroke , and myocardial infa rct ion . However , stenting is associated with a greater need for repeated revascularization Purpose : We sought to compare directly elicited valuations for EQ-5D health states between the US and UK general adult population s. Methods : We analyzed data from 2 EQ-5D valuation studies where , using similar time trade-off protocol s , values for 42 common health states were elicited from representative sample s of the US and UK general adult population s. First , US and UK population mean valuations were estimated and compared for each health state . Second , r and om-effect models were used to compare the US and UK valuations while adjusting for known predictors of EQ-5D valuations ( ie , age , sex , health state descriptors ) and to investigate whether and how the valuations differ . Results : Population mean valuations of the 42 health states ranged from −0.38 to 0.88 for the United States and from −0.54 to 0.88 for the United Kingdom , with the US mean scores being numerically higher than the UK for 39 health states ( mean difference : 0.11 ; range : −0.01 to 0.25 ) . After adjusting for the main effects of known predictors , the average difference in valuations was 0.10 ( P < 0.001 ) . The magnitude of the difference in the US and UK valuations was not constant across EQ-5D health states ; greater differences in valuations were present in health states characterized by extreme problems . Conclusions : Meaningful differences exist in directly elicited TTO valuations of EQ-5D health states between the US and UK general population s. Therefore , EQ-5D index scores generated using valuations from the US general population should be used for studies aim ing to reflect health state preferences of the US general public BACKGROUND The SF-6D is a new health state classification and utility scoring system based on 6 dimensions ( ' 6D ' ) of the Short Form 36 , and permits a " bridging " transformation between SF-36 responses and utilities . The Health Utilities Index , mark 3 ( HUI3 ) is a valid and reliable multi-attribute health utility scale that is widely used . We assessed within-subject agreement between SF-6D utilities and those from HUI3 . METHODS Patients at increased risk of sudden cardiac death and participating in a r and omized trial of implantable defibrillator therapy completed both instruments at baseline . Score distributions were inspected by scatterplot and histogram and mean score differences compared by paired t-test . Pearson correlation was computed between instrument scores and also between dimension scores within instruments . Between-instrument agreement was by intra-class correlation coefficient ( ICC ) . RESULTS SF-6D and HUI3 forms were available from 246 patients . Mean scores for HUI3 and SF-6D were 0.61 ( 95 % CI 0.60 - 0.63 ) and 0.58 ( 95 % CI 0.54 - 0.62 ) respectively ; a difference of 0.03 ( p<0.03 ) . Score intervals for HUI3 and SF-6D were ( -0.21 to 1.0 ) and ( 0.30 - 0.95 ) . Correlation between the instrument scores was 0.58 ( 95 % CI 0.48 - 0.68 ) and agreement by ICC was 0.42 ( 95 % CI 0.31 - 0.52 ) . Correlations between dimensions of SF-6D were higher than for HUI3 . CONCLUSIONS Our study casts doubt on the whether utilities and QALYs estimated via SF-6D are comparable with those from HUI3 . Utility differences may be due to differences in underlying concepts of health being measured , or different measurement approaches , or both . No gold st and ard exists for utility measurement and the SF-6D is a valuable addition that permits SF-36 data to be transformed into utilities to estimate QALYs . The challenge is developing a better underst and ing as to why these classification-based utility instruments differ so markedly in their distributions and point estimates of derived utilities The objective of this study is to evaluate the costs and health benefits of coronary artery bypass grafting ( CABG ) surgery with and without cardiopulmonary bypass ( CPB ) . R and omized controlled clinical trial is used as the design . The setting is in a single tertiary cardiothoracic center in Middlesex , UK . Participants were 168 patients ( 27 females ) requiring primary isolated CABG surgery . Patients were r and omized to have the procedure performed by a single surgeon either with CPB ( n = 84 ) or by an off-pump coronary artery bypass ( OPCAB ) surgery ( n = 84 ) . Health-related quality of life was assessed at baseline , 6 weeks , and 6 months using the World Health Organization Quality -of-Life ( WHOQOL-100 ) question naire . Mean total costs of patient management by either technique were calculated using different available key sources . A utility measure , derived from WHOQOL-100 , was used to calculate quality -adjusted life year ( QALY ) gained in each group , on basis of which a cost-effectiveness analysis was performed . The mean total costs of an OPCAB patient was 5859 pounds , whereas for a CPB patient it was 7431 pounds with a mean difference of 1572 pounds ( st and ard error [ SE ] 674 pounds ; P = 0.02 ) . Three patients died in the CPB group and two in the OPCAB group during the 6-month follow-up period . Mean QALYs over 6 months was 0.379 in the OPCAB group and 0.362 in the CPB group , but the difference was not significant ( mean difference 0.017 ; SE 0.016 ; P = 0.305 ) . OPCAB surgery offered patients in this r and omized trial similar health benefits to CPB over a 6-month period , but at a significantly less cost The Beaver Dam Health Outcomes Study ( BDHOS ) is an ongoing longitudinal cohort study of health status and health-related quality of life for a r and om sample of adults ( age range at interview was 45 to 89 years ; mean = 64.1 , SD = 10.8 ) in a community population . In a face-to-face interview lasting approximately an hour , each participant responds to several batteries of questions . Included are a history of chronic medical conditions , current medi cations , and past surgeries ; the SF-36 ( a general health-status question naire ) ; the Quality of Well-being index ; self-rated health status on a five-point scale from " excellent " to " poor " ; and evaluation of current health using the method of time tradeoffs . The authors present results from 1,356 interviews on these four principal measures , reporting mean scores by sex , by age , and for persons reporting being affected by various medical conditions . They believe data from the BDHOS will provide research ers and policy makers a reference col lection of vital statistics for health-related quality of life . Additionally , the data provide a way to compare results from studies that utilize different indices from among the four principal measures of the BDHOS . Key words : health status ; quality of life ( health-related ) ; population study ; cohort study . ( Med Decis Making 1993;13:89 - 102 OBJECTIVES To assess the acceptability and feasibility of functional tests as a gateway to angiography for management of coronary artery disease ( CAD ) , the ability of diagnostic strategies to identify patients who should undergo revascularisation , patient outcomes in each diagnostic strategy , and the most cost-effective diagnostic strategy for patients with suspected or known CAD . DESIGN A rapid systematic review of economic evaluations of alternative diagnostic strategies for CAD was carried out . A pragmatic and generalisable r and omised controlled trial was undertaken to assess the use of the functional cardiac tests : angiography ( controls ) ; single photon emission computed tomography ( SPECT ) ; magnetic resonance imaging ( MRI ) ; stress echocardiography . SETTING The setting was Papworth Hospital NHS Foundation Trust , a tertiary cardiothoracic referral centre . PARTICIPANTS Patients with suspected or known CAD and an exercise test result that required non-urgent angiography . INTERVENTIONS Patients were r and omised to one of the four initial diagnostic tests . MAIN OUTCOME MEASURES Eighteen months post-r and omisation : exercise time ( modified Bruce protocol ) ; cost-effectiveness compared with angiography ( diagnosis , treatment and follow-up costs ) . The aim was to demonstrate equivalence in exercise time between those r and omised to functional tests and those r and omised to angiography [ defined as the confidence interval ( CI ) for mean difference from angiography within 1 minute ] . RESULTS The 898 patients were r and omised to angiography ( n = 222 ) , SPECT ( n = 224 ) , MRI ( n = 226 ) or stress echo ( n = 226 ) . Initial diagnostic tests were completed successfully with unequivocal results for 98 % of angiography , 94 % of SPECT ( p = 0.05 ) , 78 % of MRI ( p < 0.001 ) and 90 % of stress echocardiography patients ( p < 0.001 ) . Some 22 % of SPECT patients , 20 % of MRI patients and 25 % of stress echo patients were not subsequently referred for an angiogram . Positive functional tests were confirmed by positive angiography in 83 % of SPECT patients , 89 % of MRI patients and 84 % of stress echo patients . Negative functional tests were followed by positive angiograms in 31 % of SPECT patients , 52 % of MRI patients and 48 % of stress echo patients tested . The proportions that had coronary artery bypass graft surgery were 10 % ( angiography ) , 11 % ( MRI ) and 13 % ( SPECT and stress echo ) and percutaneous coronary intervention 25 % ( angiography ) , 18 % ( SPECT ) and 23 % ( MRI and stress echo ) . At 18 months , comparing SPECT and stress echo with angiography , a clinical ly significant difference in total exercise time can be ruled out . The MRI group had significantly shorter mean total exercise time of 35 seconds and the upper limit of the CI was 1.14 minutes less than in the angiography group , so a difference of at least 1 minute can not be ruled out . At 6 months post-treatment , SPECT and angiography had equivalent mean exercise time . Compared with angiography , the MRI and stress echo groups had significantly shorter mean total exercise time of 37 and 38 seconds , respectively , and the upper limit of both CIs was 1.16 minutes , so a difference of at least 1 minute can not be ruled out . The differences were mainly attributable to revascularised patients . There were significantly more non-fatal adverse events in the stress echo group , mostly admissions for chest pain , but no significant difference in the number of patients reporting events . Mean ( 95 % CI ) total additional costs over 18 months , compared with angiography , were 415 pounds ( -310 pounds to 1084 pounds ) for SPECT , 426 pounds ( -247 pounds to 1088 pounds ) for MRI and 821 pounds ( 10 pounds to 1715 pounds ) for stress echocardiography , with very little difference in quality -adjusted life-years ( QALYs ) amongst the groups ( less than 0.04 QALYs over 18 months ) . Cost-effectiveness was mainly influenced by test costs , clinicians ' willingness to trust negative functional tests and by a small number of patients who had a particularly difficult clinical course . CONCLUSIONS Between 20 and 25 % of patients can avoid invasive testing using functional testing as a gateway to angiography , without substantial effects on outcomes . The SPECT strategy was as useful as angiography in identifying patients who should undergo revascularisation and the additional cost was not significant , in fact it would be reduced further by restricting the rest test to patients who have a positive stress test . MRI had the largest number of test failures and , in this study , had the least practical use in screening patients with suspected CAD , although it had similar outcomes to stress echo and is still an evolving technology . Stress echo patients had a 10 % test failure Output:	Similar findings were observed in estimates applying to general CHD . No significant improvement in model fit was found after adjusting for study -level covariates . Large between- study heterogeneity was observed in all the models investigated . The main finding of our study is the presence of large heterogeneity both within and between instrument-specific HRQoL values .
MS21349	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Engaging practicing physicians in educational strategies that reinforce guideline adoption and improve the quality of healthcare may be difficult . Push technologies such as email offer new opportunities to engage physicians in online educational reinforcing strategies . The objectives are to investigate 1 ) the effectiveness of email announcements in engaging recruited community-based primary care physicians in an online guideline reinforcement strategy design ed to promote Chlamydia screening , 2 ) the characteristics of physicians who respond to email announcements , as well as 3 ) how quickly and when they respond to email announcements . Methods Over a 45-week period , 445 recruited physicians received up to 33 email contacts announcing and reminding them of an online women 's health guideline reinforcing CME activity . Participation was defined as physician log-on at least once to the website . Data were analyzed to determine participation , to compare characteristics of participants with recruited physicians who did not participate , and to determine at what point and when participants logged on . Results Of 445 recruited physicians with accurate email addresses , 47.2 % logged on and completed at least one module . There were no significant differences by age , race , or specialty between participants and non- participants . Female physicians , US medical graduates and MDs had higher participation rates than male physicians , international medical graduates and DOs . Physicians with higher baseline screening rates were significantly more likely to log on to the course . The first 10 emails were the most effective in engaging community-based physicians to complete the intervention . Physicians were more likely to log on in the afternoon and evening and on Monday or Thursday . Conclusions Email course reminders may enhance recruitment of physicians to interventions design ed to reinforce guideline adoption ; physicians ' response to email reminders may vary by gender , degree , and country of medical training . Repetition of email communications contributes to physician online participation Introduction Critical care physicians may benefit from immediate access to medical reference material . We evaluated the feasibility and potential benefits of a h and held computer based knowledge access system linking a central academic intensive care unit ( ICU ) to multiple community-based ICUs . Methods Four community hospital ICUs with 17 physicians participated in this prospect i ve interventional study . Following training in the use of an internet-linked , up date able h and held computer knowledge access system , the physicians used the h and held devices in their clinical environment for a 12-month intervention period . Feasibility of the system was evaluated by tracking use of the h and held computer and by conducting surveys and focus group discussion s. Before and after the intervention period , participants underwent simulated patient care scenarios design ed to evaluate the information sources they accessed , as well as the speed and quality of their decision making . Participants generated admission orders during each scenario , which were scored by blinded evaluators . Results Ten physicians ( 59 % ) used the system regularly , predominantly for nonmedical applications ( median 32.8/month , interquartile range [ IQR ] 28.3–126.8 ) , with medical software accessed less often ( median 9/month , IQR 3.7–13.7 ) . Eight out of 13 physicians ( 62 % ) who completed the final scenarios chose to use the h and held computer for information access . The median time to access information on the h and held h and held computer was 19 s ( IQR 15–40 s ) . This group exhibited a significant improvement in admission order score as compared with those who used other re sources ( P = 0.018 ) . Benefits and barriers to use of this technology were identified . Conclusion An up date able h and held computer system is feasible as a means of point-of-care access to medical reference material and may improve clinical decision making . However , during the study , acceptance of the system was variable . Improved training and new technology may overcome some of the barriers we identified Abstract Objective : To underst and the factors influencing the adoption of a computerised clinical decision support system for two chronic diseases in general practice . Design : Practice based , longitudinal , qualitative interview study . Setting : Five general practice s in north east Engl and . Participants : 13 respondents ( two practice managers , three nurses , and eight general practitioners ) gave a total of 19 semistructured interviews . 40 people in practice s included in the r and omised controlled trial ( 34 doctors , three nurses ) and interview study ( three doctors , one previously interviewed ) gave feedback . Results : Negative comments about the decision support system significantly outweighed the positive or neutral comments . Three main areas of concern among clinicians emerged : timing of the guideline trigger , ease of use of the system , and helpfulness of the content . Respondents did not feel that the system fitted well within the general practice context . Experience of “ on-dem and ” information sources , which were generally more positively viewed , informed the comments about the system . Some general practitioners suggested that nurses might find the guideline content more clinical ly useful and might be more prepared to use a computerised decision support system , but lack of feedback from nurses who had experienced the system limited the ability to assess this . Conclusions : Significant barriers exist to the use of complex clinical decision support systems for chronic disease by general practitioners . Key issues include the relevance and accuracy of messages and the flexibility to respond to other factors influencing decision making in primary care . What is already known on this topic R and omised controlled trials of complex computerised decision support systems have found low rates of use and no effects on process and outcomes of care What this study adds Clinicians found a computerised decision support system for chronic disease in general practice to be difficult to use and unhelpful clinical ly It did not fit well into a general practice consultation and compared unfavourably with “ on-dem and ” information “ Active ” decision support can make clinicians aware of gaps between their own practice and “ best ” practice , but computer prompts need to be relevant and A double-blind r and omised controlled trial was conducted on a group of Hong Kong hospital clinicians . The objective was to test if a three-hour educational workshop ( with supervised h and s-on practice ) is more effective ( than no training ) to improve clinical question formulation , information-seeking skills , knowledge , attitudes , and search outcomes . The design was a post-test-only control group ; recruitment by stratified r and omization ( by profession ) , blocked at 800 . End-user training was more effective than no training in improving clinical question formulation , in raising awareness , knowledge , confidence and use of data bases , but had made no impact on preference for secondary data bases . It changed the attitude of clinicians to become more positive towards the use of electronic information services ( EIS ) . Participants had higher search performance and outcomes ( satisfaction with information obtained ( NNT = 3 ) , EIS satisfaction ( NNT = 3 ) and success in problem solving ( NNT = 4 ) ) . The workshop improved knowledge and skills in evidence -based search ing , but this effect gradually eroded with time . Search logs confirmed that follow-up is required if effects are to be sustained . Longer effects on search behaviours appear to be positive . A r and omised controlled trial is valuable in identifying cause- and -effect relations and to quantify the magnitude of the effects for management decision-making An ethnographic ( participant observation ) study was undertaken of the socio-technical processes involved in the implementation , within a r and omized controlled trial , of a home telehealth nursing service for patients with chronic obstructive pulmonary disease ( COPD ) . Ethnographic field notes were taken about technology-related tasks and the interplay between the research team and the 12 nurses who were to use the telehealth equipment . Views of the technology were linked to views of professional self-image and status . The technology was sometimes seen as unhelpful in establishing effective relationships with patients . Considerable work by all participants , over a period of months , was required to develop the technology in ways that minimized the risk to the stability of the specialist service and existing nurse – patient relationships . Our work highlights the complex problems that health professionals encounter when they try to integrate new technologies into routine service delivery . The concerns arising from the interplay of new technology with existing professional practice s and relationships go beyond simple issues of training OBJECTIVE Usage of computer re sources at the point of care has a positive effect on physician decision making . Pediatricians ' information-seeking behaviors are not well characterized . The goal of this study was to characterize quantitatively the information-seeking behaviors of general pediatricians and specifically compare their use of computers , including digital libraries , before and after an educational intervention . METHODS General pediatric residents and faculty at a US Midwest children 's hospital participated . A control ( year 1 ) versus intervention group ( year 2 ) research design was implemented . Eligible pediatrician pools overlapped , such that some participated first in the control group and later as part of the intervention . The intervention group received a 10-minute individual training session and h and out on how to use a pediatric digital library to answer professional questions . A general medical digital library was also available . Pediatricians in both the control and the intervention groups were surveyed using the critical incident technique during 2 6-month time periods . Both groups were telephoned for 1- to 2-minute interviews and were asked , " What pediatric question ( s ) did you have that you needed additional information to answer ? " The main outcome measures were the differences between the proportion of pediatricians who use computers and digital libraries and a comparison of the number of times that pediatricians use these re sources before and after intervention . RESULTS A total of 58 pediatricians were eligible , and 52 participated ( 89.6 % ) . Participant demographics between control ( N = 41 ; 89.1 % ) and intervention ( N = 31 ; 70.4 % ) were not statistically different . Twenty pediatricians were in both groups . Pediatricians were slightly less likely to pursue answers after the intervention ( 94.7 % vs 89.2 % ) ; the primary reason cited for both groups was a lack of time . The pediatricians were as successful in finding answers in each group ( 95.7 % vs 92.7 % ) , but the intervention group took significantly less time ( 8.3 minutes vs 19.6 minutes ) . After the intervention , pediatricians used computers and digital libraries more to answer their questions and spent less time using them . CONCLUSION This study showed higher rates of physician questions pursued and answered and higher rates of computer use at baseline and after intervention compared with previous studies . Pediatricians who seek answers at the point of care therefore should begin to shift their information-seeking behaviors toward computer re sources , as they are as effective but more time-efficient OBJECTIVES Information technology is a rapidly exp and ing branch of science which has affected other sciences . One example of using information technology in medicine is the Electronic Medical Records system . One medical university in Iran decided to introduce such system in its hospital . This study was design ed to identify the factors which influence the quality of medical documentation when paper-based records are replaced with electronic records . METHODS A set of 300 electronic medical records was r and omly selected and evaluated against eleven checklists in terms of documentation of medical information , availability , accuracy and ease of use . To get the opinion of the care-providers on the electronic medical records system , ten physicians and ten nurses were interviewed by using of semi-structured guidelines . The results were also compared with a prior study with 300 paper-based medical records . RESULTS The quality of documentation of the medical records was improved in areas where nurses were involved , but those parts which needed physicians ' involvement were actually worse . High workloads , shortage of bedside hardware and lack of software features were prominent influential factors in the quality of documentation . The results also indicate that the retrieval of information from the electronic medical records is easier and faster , especially in emergency situations . CONCLUSIONS The electronic medical records system can be a good substitute for the paper-based medical records system . However , according to this study , some factors such as low physician acceptance of the electronic medical record system , lack of administrative mechanisms ( for instance supervision , neglecting physicians and /or nurses in the development and implementation phases and also continuous training ) , availability of hardware as well as lack of specific software features can negatively affect transition from a paper-based system to an electronic system STUDY OBJECTIVE We introduced self-service access to the medical literature data base , MEDLINE , into clinical setting s to assess the frequency , patterns , purpose s , and success of use . DESIGN Longitudinal descriptive study . SETTING Inpatient and outpatient services of a university medical center . PARTICIPANTS All trainees and attending staff working at the service sites were invited to participate ; 158 ( 84 % ) did so . INTERVENTIONS Free online access was provided to MEDLINE through GRATEFUL MED software . Participants were offered a 2-hour introduction to online search ing and 2 hours of free search time . MEASUREMENTS AND MAIN RESULTS For each search , a computer program requested identification of the user and the question to be addressed . Search transactions were recorded automatically . Interviews were conducted after a r and om sample of search es , and search questions were given to more expert search ers to run for comparison with the original . Eighty-one percent of participants did search es on study computers , at a mean rate of 2.7 search es per month . On comparison search es , participants retrieved 55 % of the number of relevant articles retrieved by reference librarians ( P = 0.024 ) and 50 % more irrelevant articles ( P less than 0.001 ) . Forty-seven percent of search es on patient problems affected clinical decisions , but often on scanty information . CONCLUSIONS MEDLINE search ing from clinical setting s is feasible with brief training and affects clinical decisions . However , inexperienced search ers miss many relevant citations and search inefficiently . Further studies are needed to assess the impact of search ing on physician performance and patient care Background With the public ’s increased use of the Internet , the use of email as a means of communication between patients and physicians will likely increase . Yet , despite evidence of increased interest by patients , email use by physicians for clinical care has been slow . Objective To examine the factors associated with physician-patient email , and report on the physicians ’ adherence to recognized guidelines for email communication . Methods Cross-sectional survey ( March – May , 2005 ) of all primary care physicians ( n = 10253 ) , and a 25 % stratified , r and om sample of all ambulatory clinical specialists ( n = Output:	Perception of the benefits of the innovation ( system usefulness ) was the most common facilitating factor , followed by ease of use . Issues regarding design , technical concerns , familiarity with ICT , and time were the most frequent limiting factors identified .
MS21350	*TASK* the task is to summarize an input biomedical literature in six sentences *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 common question in clinical consultations is : “ For this person , what are the likely effects of one treatment compared with another ? ” The central tenet of evidence based medicine is that this task is achieved by using the best evidence combined with consideration of that person 's individual needs.1 A further question then arises : “ What is the best evidence ? ” Two recent studies in the New Engl and Journal of Medicine have caused uproar in the research community by finding no difference in estimates of treatment effects between r and omised controlled trials and non-r and omised trials . The r and omised controlled trial and , especially , systematic review s of several of these trials are traditionally the gold st and ards for judging the benefits of treatments , mainly because it is conceptually easier to attribute any observed effect to the treatments being compared . The role of non-r and omised ( observational ) studies in evaluating treatments is contentious : deliberate choice of the treatment for each person implies that observed outcomes may be caused by differences among people being given the two treatments , rather than the treatments alone . Unrecognised confounding factors can always interfere with attempts to correct for identified differences between groups . These considerations have supported a hierarchy of evidence , with r and omised controlled trials and derivatives at the top , controlled 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 A controlled intervention trial , with the purpose of testing the hypothesis that the incidence of coronary heart disease ( CHD ) could be decreased by the use of a serum-cholesterol-lowering ( SCL ) diet , was carried out in two mental hospitals near Helsinki in 1959 - 71 . The subjects were hospitalized middle-aged women . One of the hospitals received the SCL diet , ie a diet low in saturated fats and cholesterol and relatively high in poly-unsaturated fats , while the other served as the control with a normal hospital diet . Six years later the diets were reversed , and the trial was continued another six years . The use of the SCL diet was associated with markedly lowered serum cholesterol values . The incidence of CHD , as measured by the appearance of certain electrocardiographic patterns and by the occurrence of coronary deaths , was in both hospitals during the SCL-diet periods lower than during the normal-diet periods . The differences , however , failed to reach statistical significance . An examination of a number of potential confounding variables indicated that the changes in them were small and failed to account for the reduction in the incidence of CHD . Although the results of this trial do not permit firm conclusions , they support the idea that also among female population s the SCL diet exerts a preventive effect on CHD A controlled intervention trial , with the purpose of testing the hypothesis that the incidence of coronary heart disease ( CHD ) could be decreased by the use of serum-cholesterol-lowering ( SCL ) diet , was carried out in 2 mental hospitals near Helsinki in 1959 - -71 . The subjects were hospitalized middle-aged men . One of the hospitals received the SCL diet , i.e. a diet low in saturated fats and cholesterol and relatively high in polyunsaturated fats , while the other served as the control with a normal hospital diet . Six years later the diets were reversed , and the trial was continued another 6 years . The use of the SCL diet was associated with markedly lowered serum-cholesterol values . The incidence of CHD , as measured by the appearance of certain electrocardiographic patterns and by the occurrence of coronary deaths , was in both hospitals during the SCL-diet periods about half that during the normal-diet periods . An examination of a number of potential confounding variables indicated that the changes in them were small and failed to account for the considerable reduction in the incidence of CHD . It is concluded that the use of the serum-cholesterol-lowering diet exerted a substantial preventive effect on CHD Output:	There were no differences in all-cause mortality and non-significant differences in CHD mortality , result ing from the dietary interventions . The reductions in mean serum cholesterol levels were significantly higher in the intervention groups ; this did not result in significant differences in CHD or all-cause mortality . Dietary recommendations were introduced for 220 million US and 56 million UK citizens by 1983 , in the absence of supporting evidence from RCTs
MS21351	*TASK* the task is to summarize an input biomedical literature in six sentences *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 therapeutic options for patients with polymyositis or dermatomyositis that is resistant to corticosteroids are limited , unproved , and often toxic . Uncontrolled trials concluded that both plasma exchange and leukapheresis are beneficial , but despite the considerable use of these approaches , proof of their efficacy is lacking . METHODS Thirty-nine patients with definite polymyositis or dermatomyositis were r and omly assigned to receive plasma exchange ( replacement of one volume of plasma with 5 percent albumin in saline ) , leukapheresis ( removal of 5 x 10(9 ) to 10 x 10(9 ) lymphocytes ) , or sham apheresis in a double-blind manner , with 12 treatments given over a one-month period . Muscle strength , functional capacity , and serum levels of muscle-associated enzymes were measured before and after the 12 procedures . RESULTS In each group 3 of 13 patients had improvements in strength and functional capacity . The condition of 3 patients treated with leukapheresis and 1 treated with plasma exchange deteriorated , and it was unchanged in the other 26 patients . Adverse effects of apheresis included the need for a central venous catheter ( 9 patients ) , major vasovagal episodes ( 3 patients ) , and severe citrate reactions ( 2 patients ) . Despite the occurrence of significant reductions in the serum levels of muscle enzymes with plasma exchange ( P less than 0.001 ) and significant decreases in lymphocyte counts with leukapheresis ( P = 0.002 ) , there were no significant differences among the three treatment groups in the final muscle strength or functional capacity of the patients . CONCLUSIONS As treatments for corticosteroid-resistant polymyositis or dermatomyositis , leukapheresis and plasma exchange are no more effective than sham apheresis BACKGROUND Dermatomyositis is a clinical ly distinct myopathy characterized by rash and a complement-mediated microangiopathy that results in the destruction of muscle fibers . In some patients the condition becomes resistant to therapy and causes severe physical disabilities . METHODS We conducted a double-blind , placebo-controlled study of 15 patients ( age , 18 to 55 years ) with biopsy-proved , treatment-resistant dermatomyositis . The patients continued to receive prednisone ( mean daily dose , 25 mg ) and were r and omly assigned to receive one infusion of immune globulin ( 2 g per kilogram of body weight ) or placebo per month for three months , with the option of crossing over to the alternative therapy for three more months . Clinical response was gauged by assessing muscle strength , neuromuscular symptoms , and changes in the rash . Changes in immune-mediated muscle abnormalities were determined by repeated muscle biopsies . RESULTS The eight patients assigned to immune globulin had a significant improvement in sores of muscle strength ( P < 0.018 ) and neuromuscular symptoms ( P < 0.035 ) , whereas the seven patients assigned to placebo did not . With crossovers a total of 12 patients received immune globulin . Of these , nine with severe disabilities had a major improvement to nearly normal function . Their mean muscle-strength scores increased from 74.5 to 84.7 , and their neuromuscular symptoms improved . Two of the other three patients had mild improvement , and one had no change in his condition . Of 11 placebo-treated patients , none had a major improvement , 3 had mild improvement , 3 had no change in their condition , and 5 had worsening of their condition . Repeated biopsies in five patients of muscles whose strength improved to almost normal showed an increase in muscle-fiber diameter ( P < 0.04 ) , an increase in the number and a decrease in the diameter of capillaries ( P < 0.01 ) , resolution of complement deposits on capillaries , and a reduction in the expression of intercellular adhesion molecule 1 and major-histocompatibility-complex class I antigens . CONCLUSIONS High-dose intravenous immune globulin is a safe and effective treatment for refractory dermatomyositis High-dose intravenous immunoglobulin ( IVIG ) therapy has been effective in treating various autoimmune and systemic inflammatory diseases . Here , we assessed the efficacy and safety of IVIG therapy with polyethylene glycol-treated human IgG ( drug code GB-0998 ) for patients with corticosteroid-refractory polymyositis ( PM ) and dermatomyositis ( DM ) by means of a r and omized , double-blind , placebo-controlled study . We r and omly assigned 26 subjects ( 16 PM and 10 DM ) to receive either GB-0998 or placebo . Intragroup comparison in the GB-0998 group showed statistically significant improvements due to GB-0998 administration in the primary endpoint ( manual muscle test score ) and secondary endpoints ( serum creatine kinase level and activities of daily living score ) . However , significant improvements were also found in the placebo group , and comparison of the GB-0998 group with the placebo group did not show any significant difference between the groups . We discuss possible reasons for the absence of a clear intergroup difference in efficacy . Nineteen adverse drug reactions were observed in 11 of 26 subjects ( 42.3 % ) , of which 2 events ( decreased muscle strength and increased serum creatine kinase ) were assessed as serious ; however , they are previously known events . These results indicate that GB-0998 can be safely used with the same pre caution s as other current IVIG therapy Objective . Ciclosporin and MTX are used in idiopathic inflammatory myopathies ( DM and PM ) when patients incompletely respond to glucocorticoids . Their effectiveness is unproved in r and omized controlled trials ( RCTs ) . We evaluated their benefits in a placebo-controlled factorial RCT . Methods . A 56-week multicentre factorial- design double-blind placebo-controlled RCT compared steroids alone , MTX ( 15–25 mg weekly ) plus steroids , ciclosporin ( 1–5 mg/kg/day ) plus steroids and all three treatments . It enrolled adults with myositis ( by Bohan and Peter criteria ) with active disease receiving corticosteroids . Results . A total of 359 patients were screened and 58 r and omized . Of the latter , 37 patients completed 12 months of treatment , 7 were lost to follow-up and 14 discontinued treatment . Patients completing 12 months of treatment showed significant improvement ( P < 0.001 on paired t-tests ) in manual muscle testing ( 14 % change ) , walking time ( 22 % change ) and function ( 9 % change ) . Intention to treat and completer analyses indicated that ciclosporin monotherapy , MTX monotherapy and ciclosporin/MTX combination therapy showed no significant treatment effects in comparison with placebo . Conclusion . Neither MTX nor ciclosporin ( by themselves or in combination ) improved clinical features in myositis patients who had incompletely responded to glucocorticoids . Trial Registration : International St and ard R and omized Controlled Trial Number Register ; http://www.controlled-trials.com/ ; IS RCT OBJECTIVES To test the utility of a new , easy to administer instrument for assessing activities of daily living in patients with amyotrophic lateral sclerosis ( ALS ) , to vali date its accuracy , and to assess its ability to record disease progression in patients with ALS against other functional scales , quantitative isometric muscle testing , and global assessment scales . DESIGN Serial assessment s of patients who presented to four ALS treatment centers in two multicenter studies . PATIENTS Study 1 ( cross-sectional ) evaluated 75 consecutive patients who presented to four ALS treatment centers during a 2-month period . Study 2 ( longitudinal ) evaluated the progression of 53 patients who were enrolled in a multicenter , phase I-II clinical trial of recombinant human ciliary neurotrophic factor for treatment of ALS . OUTCOME MEASURES The ALS Functional Rating Scale ( ALSFRS ) was compared with quantitative myometry and with other measures of daily function in patients with ALS both cross-sectionally and longitudinally . RESULTS The first study of 75 patients evaluated the internal consistency , the test-retest reliability , and the construct validity of the ALSFRS . Internal consistency and test-retest reliability were high . Patient self-rating of upper- and lower-extremity-dependent tasks were highly correlated with measures of upper- and lower-extremity strength , respectively . Thus , the ALSFRS has good construct validity . In the second study , ALSFRS scores declined in t and em with deterioration in motor and pulmonary function , indicating its sensitivity to change . CONCLUSIONS The ALSFRS is a useful instrument for evaluation of functional status and functional change in patients with ALS . Its results are in close agreement with objective measures of muscle strength and pulmonary function . The ALSFRS may be used as a screening measure for entry into clinical trials , as a surrogate measure of function in situations in which muscle strength can not be measured directly , or as an adjunct to myometry To determine if high-dose pulsed dexamethasone is more effective and safer than daily high-dose prednisolone in treatment-naive adult patients with inflammatory myopathies ( sporadic inclusion body myositis excluded ) we performed a multicenter , double-blind r and omised controlled clinical trial with 18 months follow-up . Sixty-two patients were r and omised into 28-day cycles of oral high-dose dexamethasone or daily high-dose prednisolone . Primary outcome measures included ( 1 ) seven point composite score of six clinical ly relevant outcomes and ( 2 ) ( time-to ) remission and ( time-to ) relapse . No difference between both treatment groups on the composite score was found . Side-effects occurred significantly less frequently in the dexamethasone group . Median time to relapse was 60 ( 2.9 ) weeks in the prednisolone and 44 ( 4.7 ) weeks in the dexamethasone group ( log-rank test p=0.03 ) . In conclusion , pulsed high-dose oral dexamethasone is not superior to daily prednisolone as first-line treatment of idiopathic inflammatory myopathies , but is a good alternative by causing substantially fewer side-effects Two groups of patients with polymyositis have been followed for approximately 3 years . One group was treated with prednisone alone and the other with prednisone plus azathioprine . Although the polymyositis of both groups has improved , no statistically significant difference was noted at the end of 3 months , as previously reported . Longer followup , however , has shown that the group given prednisone plus azathioprine has improved more with respect to functional disability ; this group also requires less prednisone for disease control A controlled , prospect i ve , double-blind , therapeutic trial of azathioprine was conducted in the initial therapy of polymyositis . Sixteen patients received 60 mg prednisone per day plus either azathioprine ( 2 mg/kg of body weight per day ) or placebo for a period of 3 months . Creatine phosphokinase ( CPK ) levels fell to normal slightly sooner in the placebo group , but not significantly so . The azathioprine group did not become significantly stronger ( P = 0.58 ) and did not manifest significantly greater improvement of histopathologic features of muscle ( P = 0.80 ) than the placebo group . Initial CPK elevations were significantly related to the degree of muscle inflammation ( P = 0.037 ) , but this was not the case at 3 months ( P greater than 0.05 ) . Normalization of the CPK could not be equated with disease control . Type II fiber atrophy , attributed to steroid therapy , was more marked in women than in men ( P less than 0.03 ) OBJECTIVE To assess the safety and efficacy of rituximab in a r and omized , double-blind , placebo-phase trial in adult and pediatric myositis patients . METHODS Adults with refractory polymyositis ( PM ) and adults and children with refractory dermatomyositis ( DM ) were enrolled . Entry criteria included muscle weakness and ≥2 additional abnormal values on core set measures ( CSMs ) for adults . Juvenile DM patients required ≥3 abnormal CSMs , with or without muscle weakness . Patients were r and omized to receive either rituximab early or rituximab late , and glucocorticoid or immunosuppressive therapy was allowed at study entry . The primary end point compared the time to achieve the International Myositis Assessment and Clinical Studies Group preliminary definition of improvement ( DOI ) between the 2 groups . The secondary end points were the time to achieve ≥20 % improvement in muscle strength and the proportions of patients in the early and late rituximab groups achieving the DOI at week 8 . RESULTS Among 200 r and omized patients ( 76 with PM , 76 with DM , and 48 with juvenile DM ) , 195 showed no difference in the time to achieving the DOI between the rituximab late ( n = 102 ) and rituximab early ( n = 93 ) groups ( P = 0.74 by log rank test ) , with a median time to achieving a DOI of 20.2 weeks and 20.0 weeks , respectively . The secondary end points also did not significantly differ between the 2 treatment groups . However , 161 ( 83 % ) of the r and omized patients met the DOI , and individual CSMs improved in both groups throughout the 44-week trial . CONCLUSION Although there were no significant differences in the 2 treatment arms for the primary and secondary end points , 83 % of adult Output:	Although no treatment can be recommended on the basis of this review , improved outcomes were demonstrated with a number of agents including methotrexate , azathioprine , ciclosporin , rituximab , and intravenous immunoglobulin . Plasmapheresis and leukapheresis were of no apparent benefit .
MS21352	*TASK* the task is to summarize an input biomedical literature in six sentences *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 sought to compare two methods of notifying sex partners of subjects infected with the human immunodeficiency virus ( HIV ) or persons who had shared needles with them ( needle-sharing partners ) : " patient referral , " in which the responsibility for notifying partners was left to the patient , and " provider referral , " in which providers attempted to notify partners . METHODS Names of sex partners and needle-sharing partners and information on how to locate them were obtained from consenting HIV-infected subjects identified in the HIV-testing programs at three public health departments in North Carolina . The subjects were r and omly assigned to a patient-referral group ( in which patients had the initial responsibility for notifying their partners ) or a provider-referral group ( in which the study counselor notified the partners ) . The success of attempts to notify partners was monitored by means of interviews with counselors conducted both in the field and at the health department . RESULTS Of 534 HIV-positive persons identified at the health departments , 247 ( 46 percent ) did not return for counseling after the test , 8 were counseled outside the study , and 117 ( 22 percent ) were ineligible . Of the 162 invited to participate , 88 ( 54 percent ) declined and 74 ( 46 percent ) agreed . The subjects were mostly male ( 69 percent ) , black ( 87 percent ) , homosexual or bisexual ( 76 percent of the men ) , and had a median age of 30 years . Thirty-nine were assigned to the provider-referral group and 35 to the patient-referral group . In the provider-referral group 78 of 157 partners ( 50 percent ) were successfully notified , whereas in the patient-referral group only 10 of 153 ( 7 percent ) were notified . Of the partners notified by the counselors , 94 percent were not aware that they had been exposed to HIV . Overall , 23 percent of the partners notified and tested were HIV-positive . CONCLUSIONS In this trial , leaving the notification of partners up to the subjects ( patient referral ) was quite ineffective , despite the North Carolina law requiring that partners be notified . Partner notification by public health counselors ( provider referral ) was significantly more effective . Although the effectiveness of notification procedures is constrained by the accuracy of the information provided by HIV-infected patients , counselors who notify the partners of an infected patient can refer them to educational , medical , and support services targeted to persons at high risk for HIV infection and may encourage the adoption of less risky behavior OBJECTIVE This analysis describes the Outreach-Assisted Model of Partner Notification , an innovative strategy for encouraging seropositive injecting drug users ( IDUs ) to inform their partners of shared human immunodeficiency virus ( HIV ) exposure . The analysis focuses on two core components of the notification process : the identification of at-risk partners and preferences for self-tell vs. outreach assistance in informing partners of possible exposure to the virus . METHODS Using community outreach techniques , 386 IDUs were recruited for HIV pretest counseling , testing , and partner notification over a 12-month period . Of these , 63 tested HIV seropositive , and all but three returned for their test results . The 60 who were informed of their serostatus were r and omly assigned to either a minimal or an enhanced intervention condition . Participants assigned to the minimal ( self-tell ) group were strongly encouraged to inform their partners of possible exposure . Those assigned to the enhanced ( outreach-assisted ) group had the option of either informing one or more of their partner(s ) themselves or choosing to have the project 's outreach team do so . RESULTS Together , the 60 index persons who received their results provided names or at least one piece of locating information for a total of 142 partners with whom they perceived having shared possible exposure to the virus within the past five years . By itself , drug use accounted for half of all partners named . Sexual behavior alone accounted for 25 % of named partners . Eighty-two percent of the enhanced group preferred to have the outreach team tell at least one partner ; the team was requested to notify 71 % of the total number of partners whom this group named . CONCLUSIONS Findings suggest that IDUs want to notify their partners of shared HIV exposure . Outreach assistance was the preferred mode in the majority of cases . Exp and ing traditional community-based HIV outreach activities to include delivering street-based counseling , test , a partner notification appears to be a positive and workable prevention strategy Urogenital infections with Chlamydia trachomatis are widespread and usually asymptomatic . Major complications from infection include ectopic pregnancies and female infertility.1 Although contact tracing reduces the prevalence of chlamydia infection,2 the test rate among partners is often low , partly because male contacts have to have a urethral swab taken by a doctor . As the polymerase chain reaction can successfully detect infection in urine sample s,3 we investigated whether the test rate could be increased by asking the male contacts of infected women to send a urine sample directly from home to a laboratory instead of having a doctor take a urethral swab . Ninety six women with C trachomati s infection seen in general practice s in Aarhus County , Denmark , were r and omly divided according to their date of birth into an intervention group ( 45 patients ) and a Objective : To determine the cost and effectiveness of three approaches to partner notification for infectious syphilis . Study Design : People with syphilis were r and omly assigned to : ( 1 ) notification of partners by patients themselves within 2 days or disease intervention specialists would notify them ; ( 2 ) immediate notification by intervention specialist ; or ( 3 ) immediate notification by intervention specialists , who had the option of drawing blood in the field . Costs of intervention specialists ' time , travel , and overhead were measured . Intention‐to‐treat analysis measured outcomes per r and omized index patient . Results : From December , 1990 through March , 1993 , 1,966 index patients with syphilis ( primary 9 % ; secondary 18 % ; and early latent 73 % ) were r and omized in Broward County ( Ft . Lauderdale ) , Florida ( 1,191 ) ; Tampa , Florida ( 569 ) ; and Paterson , New Jersey ( 206 ) . Index patients reported 11,272 potentially exposed partners and sufficient information to initiate investigations for 2,761 . Of these , 2,236 were located , 367 had newly identified infections , and 870 others received preventive treatment . The three partner notification approaches had similar success locating partners ( 1.1–1.2 per index patient ) and treating partners ( 0.61–0.67 per index ) . The cost was $ 317 to $ 362 per partner treated ; the optimal strategy differed by study site . Conclusions : Partner notification identified many infected and potentially infected people . The cost and effectiveness of the three types of provider notification were similar . Alternative approaches are needed to reach infected partners who could not be notified Background : Sexually transmitted diseases ( STD ) are a major health problem in Zambia . Partner notification , which is a recommended strategy to decrease STD , must be improved . Goal : To assess whether individual counseling of patients with STD , combined with contact slip(s ) , had any impact on the proportion of sex partners traced in an urban setting in Zambia . Study Design : A r and omized trial comprised of 94 women and 302 men with STD . Results : Women and men in the intervention group informed more partners than did those in the control group . In the intervention group , 1.8 partners per man was treated compared to 1.2 in the control group ( P < 0.001 ) . There was no difference between the two groups of women . There was a gradual decline from numbers of partners informed to numbers of partners treated according to the patient to number of contact slips filed . Conclusions : Individual counseling of men with STD improved partner notification Introduction Gonorrhea has emerged recently as an epidemic disease of major proportions in the United States , with more than one million cases reported to state and local health departments in 1975.1 True incidence is unknown , but significant under-reporting is likely . A control program facing over a million cases per year must choose the general focus and specific techniques that best utilize its limited re sources . Except in some special geographic areas , interviewing and contact investigation of a significant proportion of the infected population appears to be an insurmountable task . Our purpose was to examine the efficacy of an alternative to the st and ard case interview and investigation . Although we recognized from the outset that a short-term evaluation could not provide data on disease control , we were able to evaluate the ability of the alternative to detect new cases , and on that basis we developed a sense of its comparative effectiveness and cost The impact of a ten-minute , soap opera-style videotape on knowledge and treatment behavior of black men with gonorrhea was tested in r and omized clinical trials . The videotape , shown to individual patients after diagnosis , produced a sizeable increase in the percentage of patients who returned for their test-of-cure examination : while only 43.3 % of control group patients returned , 53.5 % of those in the videotape group did so ; chi 2(1 ) = 9.0 ; P less than 0.003 . In a follow-up study , similar results were found : videotape group ( 59.0 % ) , control group ( 39.1 % ) ; chi 2(1 ) = 6.2 ; P less than 0.015 . The videotape also produced large , significant increases in patient knowledge , as measured by a test administered during patients ' clinic visit ( P less than 0.0001 ) . No measureable effect of the videotape was detected on patients ' willingness to refer sexual contacts for treatment . The findings suggest that clinic-based educational material s , particularly soap opera-style videotapes that engender audience identification , create emotional significance for the viewer , and model requisite communication skills , may have a significant role to play in control of sexually transmitted diseases Output:	The review found moderately strong evidence that : ( 1 ) provider referral alone , or the choice between patient and provider referral , when compared with patient referral among patients with HIV or any STD , increases the rate of partners presenting for medical evaluation ; ( 2 ) contract referral , when compared with patient referral among patients with gonorrhoea , results in more partners presenting for medical evaluation ; ( 3 ) verbal , nurse-given health education together with patient-centred counselling by lay workers , when compared with st and ard care among patients with any STD , results in small increases in the rate of partners treated .
MS21353	*TASK* the task is to summarize an input biomedical literature in six sentences *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 compare the efficacy of cediranib ( a vascular endothelial growth factor receptor tyrosine kinase inhibitor [ VEGFR TKI ] ) with that of bevacizumab ( anti-VEGF-A monoclonal antibody ) in combination with chemotherapy as first-line treatment for advanced metastatic colorectal cancer ( mCRC ) . PATIENTS AND METHODS HORIZON III [ Cediranib Plus FOLFOX6 Versus Bevacizumab Plus FOLFOX6 in Patients With Untreated Metastatic Colorectal Cancer ] had an adaptive phase II/III design . Patients r and omly assigned 1:1:1 received mFOLFOX6 [ oxaliplatin 85 mg/m(2 ) and leucovorin 400 mg/m(2 ) intravenously followed by fluorouracil 400 mg/m(2 ) intravenously on day 1 and then continuous infusion of 2,400 mg/m(2 ) over the next 46 hours every 2 weeks ] with cediranib ( 20 or 30 mg per day ) or bevacizumab ( 5 mg/kg every 14 days ) . An independent end-of-phase II analysis concluded that mFOLFOX6/cediranib 20 mg met predefined criteria for continuation ; subsequent patients received mFOLFOX6/cediranib 20 mg or mFOLFOX6/bevacizumab ( r and omly assigned 1:1 ) . The primary objective was to compare progression-free survival ( PFS ) . RESULTS In all , 1,422 patients received mFOLFOX6/cediranib 20 mg ( n = 709 ) or mFOLFOX6/bevacizumab ( n = 713 ) . Primary analysis revealed no significant difference between arms for PFS ( hazard ratio [ HR ] , 1.10 ; 95 % CI , 0.97 to 1.25 ; P = .119 ) , overall survival ( OS ; HR , 0.95 ; 95 % CI , 0.82 to 1.10 ; P = .541 ) , or overall response rate ( 46.3 % v 47.3 % ) . Median PFS and OS were 9.9 and 22.8 months for mFOLFOX6/cediranib and 10.3 and 21.3 months for mFOLFOX6/bevacizumab . The PFS upper 95 % CI was outside the predefined noninferiority limit ( HR < 1.2 ) . Common adverse events with more than 5 % incidence in the cediranib arm included diarrhea , neutropenia , and hypertension . Cediranib-treated patients completed fewer chemotherapy cycles than bevacizumab-treated patients ( median 10 v 12 cycles ) . Patient-reported outcomes ( PROs ) were significantly less favorable in cediranib-treated versus bevacizumab-treated patients ( P < .001 ) . CONCLUSION Cediranib activity , in terms of PFS and OS , was comparable to that of bevacizumab when added to mFOLFOX6 ; however , the predefined boundary for PFS noninferiority was not met . The cediranib safety profile was consistent with previous studies but led to less favorable PROs compared with bevacizumab . Investigation of oral TKIs in CRC continues BACKGROUND A week on/week off capecitabine schedule with oxaliplatin/bevacizumab was evaluated in patients with metastatic colorectal cancer ( mCRC ) . PATIENTS AND METHODS Forty patients were required . The projected median progression-free survival ( PFS ) was 12 months ( 81 % power , 1-sided level 0.1 log-rank test ) . Capecitabine dose was 2500 mg/m(2)/day on days 1 - 7 ( n = 11 ) and was increased to 3000 mg/m(2)/day ( n = 29 ) in combination with oxaliplatin ( 85 mg/m(2 ) ) and bevacizumab ( 5 mg/kg ) . Cycles were repeated every 2 weeks . RESULTS Patient characteristics included Eastern Cooperative Oncology Group ( ECOG ) performance status 0 ( n = 24 ) or 1 ( n = 15 ) ; median age of 62 years ( range , 38 - 81 years ) . Median cycles administered were 7 ( range , 125 ) , corresponding to 3.5 months ' treatment duration . Pertinent grade 3/4 toxicities seen were diarrhea ( 18 % ) , h and -foot syndrome ( 10 % ) , and peripheral neuropathy ( 10 % ) . Bowel perforation in 1 patient ( 3 % ) and 1 death due to a cerebral hemorrhage ( 3 % ) were noted . Response rate ( RR ) was 38 % ( 1 complete and 14 partial responses ) . Median PFS was 8.6 months ( 95 % confidence interval [ CI ] , 4.7 - 10.2 months ) . Median overall survival was 17.2 months ( 95 % CI , 10.4 - 24.2 months ) . CONCLUSION The first US experience of capecitabine to our knowledge ( 3000 mg/m(2 ) on days 1 - 7 ) in combination with oxaliplatin/bevacizumab in mCRC does not appear to have advantages compared with current st and ard first-line mCRC treatment regimens Purpose The addition of bevacizumab to oxaliplatin-based chemotherapy significantly improved progression-free survival ( PFS ) in patients with metastatic colorectal cancer ( CRC ) . An increased risk of arterial thromboembolic events has been observed in some trials in older patients , and the potential benefit of a maintenance therapy with bevacizumab alone has not been clearly demonstrated . This phase II study was design ed to evaluate the efficacy and safety of XELOX ( capecitabine plus oxaliplatin ) plus bevacizumab followed by bevacizumab alone in elderly patients with advanced CRC . Methods Treatment consisted of bevacizumab 7.5 mg/kg and oxaliplatin 130 mg/m2 on day 1 , plus capecitabine 1,000 mg/m2 twice daily on days 1–14 , every 3 weeks up to a maximum of 8 cycles . Patients then received maintenance therapy consisting of bevacizumab alone ( 7.5 mg/kg ) once every 3 weeks up to disease progression . The primary study end-points were safety and response rate . Results A total of 44 patients were recruited . In an intention-to-treat analysis , the overall response rate was 52 % [ 95 % confidence interval ( CI ) 37 to 68 % ] , with 86 % of patients achieving disease control . Median PFS and overall survival were 11.5 months ( 95 % CI 10.0–12.9 months ) and 19.3 months ( 95 % CI 16.5–22.1 months ) , respectively . In all , 10 patients ( 23 % ) had grade 3/4 adverse events ( AEs ) , the most common being diarrhea ( 9 % ) , neutropenia ( 7 % ) , peripheral neuropathy ( 7 % ) , and stomatitis ( 7 % ) . No patients died because of treatment-related AEs . The rate of bevacizumab-related AEs ( hypertension , thromboembolic events , and gastrointestinal perforation ) was consistent with that reported earlier in the general CRC population . Conclusion The combination of XELOX and bevacizumab is effective and has a manageable tolerability profile when administered to elderly patients with advanced CRC . Maintenance therapy with single-agent bevacizumab may be considered to extend PFS in this setting of patients Summary Purpose To assess safety and efficacy of folinic acid , 5-fluorouracil , gemcitabine ( FFG ) and folinic acid , fluorouracil , oxaliplatin ( FOLFOX4 ) regimens with added bevacizumab as first-line treatment in patients with advanced colorectal cancer ( CRC ) . Patients and Methods Patients with Stage III unresectable or Stage IV adenocarcinoma of the colon or rectum were r and omly assigned to either FFG weekly for 6 weeks of an 8-week cycle or FOLFOX4 every 2 weeks . After FDA approval , bevacizumab 5 mg/kg was added every 2 weeks . Treatment continued until disease progression . Planned enrollment was 190 patients . Primary endpoint was overall response rate ( ORR ) ; secondary endpoints included evaluation of adverse events , time to progression ( TTP ) , and overall survival ( OS ) . Disease Control Rate ( DCR ; % of patients with complete or partial responses or stable disease ) was a post hoc analysis . Results The trial was stopped prematurely due to low enrollment . Of 84 enrolled patients ( 42 to each arm ) , 36 patients ( 18 in each arm ) received bevacizumab . ORR was greater ( P = .002 ) for FOLFOX4 ( 17/42 ; 40.5 % ) than for FFG ( 4/42 ; 9.5 % ) ; however , TTP , OS , and DCR results were not statistically different comparing FOLFOX4 and FFG . Peripheral neuropathy was more frequent ( P = < .001 ) with FOLFOX4 ( 18/42 ; 42.9 % ) than with FFG ( 1/42 ; 2.4 % ) . Conclusions FFG and FOLFOX4 were generally well tolerated . Based on ORR , FOLFOX4 was superior to FFG . However , differences in TTP and OS comparing regimens were inconclusive . General use of gemcitabine as a biomodulator of 5-fluorouracil in CRC can not be recommended at this time and the regimen remains investigational BACKGROUND Cetuximab ( C ) , alone or with irinotecan , demonstrates activity in irinotecan-refractory colorectal cancer ( CRC ) . Activity of 5-fluorouracil ( 5-FU ) , leucovorin ( L ) , and bevacizumab ( B ) , and preliminary data of cetuximab + bevacizumab , and toxicity profiles suggests that FOLF-CB ( 5-FU , L , C+B ) may have activity with a favorable toxicity profile as first-line therapy . METHODS Eligible patients were r and omized at registration to either arm A ( mFOLFOX6-B ) ( modified , 5-FU . L ( folinic acid ) , oxaliplatin ( O ) + bevacizumab ) , administered days 1 and 15 of each 28-day cycle as bevacizumab 5 mg/kg , oxaliplatin 85 mg/m(2 ) , leucovorin 400 mg/m(2 ) , and 5-FU 400 mg/m(2 ) then 1200 mg/m(2)/day for 48 hours , or arm B ( FOLF-CB ) , which included bevacizumab , leucovorin , and 5-FU as in arm A and cetuximab 400 mg/m(2 ) day 1 cycle 1 ; all other weekly cetuximab doses were 250 mg/m(2 ) . RESULTS Two hundred forty-seven patients ( arm A/arm B 124/123 ) were enrolled , and 239 were treated ( 118/121 ) . Twelve-month progression-free survival ( PFS ) was 45%/32 % , objective response rates ( ORR ) ( complete response [ CR ] + partial response [ PR ] ) were 52%/41 % , disease control rates ( CR+PR+stable disease [ SD ] ) were 87%/83 % , and median overall survival ( OS ) was 21/19.5 months , respectively . Grade 3 - 4 neutropenia was higher in arm A ( 28%/7 % ) , as was grade 3 fatigue ( 12%/3 % ) , and grade 3 neuropathy ( 11%/ < 1 % ) , whereas acneiform rash was confined to arm B. Retrospective analysis of KRAS mutational status did not demonstrate KRAS as a meaningful determinant of activity , except in arm B patients with KRAS-mutated tumors , which result ed in inferior PFS . Patient satisfaction favored the control ( mFOLFOX6-B ) . CONCLUSION FOLF-CB was not superior to mFOLFOX6-B in terms of 12-month PFS and ORR , and was not more acceptable to patients . This trial supports the conclusion of other recently reported trials that concurrent cetuximab+bevacizumab should not be routinely used in metastatic CRC Output:	XELOX + B and FOLFOX + B are active combinations as first-line treatment of advanced CRC . Both the XELOX + B and the FOLFOX + B arms represent 2 of the cornerstone combinations when B is used as first-line therapy
MS21354	*TASK* the task is to summarize an input biomedical literature in six sentences *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 r and omized clinical trial was design ed to compare the effects of a theory-based coping effectiveness training ( CET ) intervention with an active informational control ( HIV-Info ) condition and a waiting-list control ( WLC ) condition on psychological distress and positive mood in HIV-seropositive gay men . Material s and Methods The authors recruited 149 self-identified gay or bisexual men who were 21 to 60 years of age , reported depressed mood , and had CD4 levels of 200 to 700 cells/mm3 . CET and HIV-Info participants attended 10 90-minute group sessions during the 3-month intervention phase and six maintenance sessions over the remainder of the year . Participants were assessed at baseline and at 3 , 6 , and 12 months . Data were collected 1992 to 1994 , before the introduction of HAART . Analyses were based on the 128 participants who completed the 3-month assessment . Results After the 3-month intervention phase , when compared with HIV-Info , CET participants showed significantly greater decreases in perceived stress and burnout , and regression analyses indicated that significant increases in coping self-efficacy mediated the improvements in perceived stress and burnout . Compared with WLC , CET participants also showed significantly greater decreases in anxiety , and regression analyses indicated that significant increases in positive states of mind mediated the improvements in anxiety . Significant treatment group differences for positive morale were maintained at 6 and 12 months . In addition , optimism continued to increase in the CET and HIV-Info treatment groups during the maintenance phase . Conclusions CET can be an effective strategy for managing psychological distress and improving positive psychological states in patients confronting chronic illness Mounting evidence suggests that smokers living with HIV/AIDS have a significantly increased risk of numerous adverse health outcomes ( both AIDS- and non-AIDS-related ) compared with HIV-positive nonsmokers . Therefore , efforts to design and implement effective cessation programs for this ever-growing special population are warranted . The present study assessed the effects of a cell phone intervention ( CPI ) on hypothesized mediators ( i.e. , changes in depression , anxiety , social support , and self-efficacy ) demonstrated to influence cessation outcomes in other population s. Ninety-five participants from an inner-city AIDS clinic were r and omized to receive either the CPI or recommended st and ard of care ( RSOC ) smoking cessation treatment . Participants r and omized to the RSOC group ( n=47 ) received brief advice to quit , a 10-week supply of nicotine patches , and self-help material s. Participants r and omized to the CPI group ( n=48 ) received RSOC components plus a series of eight proactive counseling sessions delivered via cell phones . A series of regression analyses ( linear and logistic ) was used to assess the relationships between treatment group , the hypothesized mediators , and biochemically confirmed smoking cessation outcomes . Results indicated that the CPI group experienced greater reductions in anxiety and depression , and increases in self-efficacy compared with the RSOC group . Further , changes in depression , anxiety , and self-efficacy weakened the association between treatment group and cessation outcome . The mediator hypothesis , however , for social support was rejected , as the difference score was not significantly associated with treatment group . These results suggest that the efficacy of the CPI is at least partially mediated by its ability to decrease symptoms of distress while increasing self-efficacy We wished to determine the short-term safety and efficacy of a Chinese medicinal herb preparation in treating symptoms of human immunodeficiency virus ( HIV ) infection in a 12-week r and omized , double-blind , placebo-controlled clinical trial in a University-affiliated acquired immunodeficiency syndrome ( AIDS ) clinic at a public general hospital . Thirty adults with symptomatic HIV infection , no previous AIDS-defining diagnosis , and CD4 + counts of 0.200 - 0.499 x 10(9)/L ( 200 - 499/mm3 ) received 28 tablets each day of either a st and ardized oral preparation of 31 Chinese herbs or a cellulose placebo . Primary outcome measures were changes in life satisfaction , perceived health , and number and severity of symptoms . Other outcomes included adherence , and changes in weight , CD4 + count , depression , anxiety , physical and social function , and mental health . Two placebo- and no herb-treated subjects had mild adverse events ( AE ) . Subjects on both arms reported taking 94 % of prescribed tablets . No differences between treatment groups reached the p < 0.05 level . Life satisfaction improved in herb-treated [ + 0.86 , 95 % confidence interval ( CI ) : + 0.29 , + 1.43 ] but not in placebo-treated subjects ( + 0.20 , 95 % CI -0.35 , + 0.75 ) . Number of symptoms was reduced in subjects receiving herbs ( -2.2 , 95 % CI -4.1 , -0.3 ) but not in those receiving placebo ( -0.3 , 95 % CI -3.2 , + 2.7 ) . There were trends toward greater improvements among herb-treated subjects on all symptom subscales except dermatologic . Believing that one was receiving herbs was strongly associated with reporting that the treatment had helped ( p < 0.005 ) , but not with changes in life satisfaction or symptoms . There were improvements in life satisfaction and symptoms among subjects receiving the herbal therapy . Whether Chinese herbs are effective in the management of symptomatic HIV infection can be adequately addressed only by larger trials of longer duration Background People who are HIV-positive now live longer when they have contracted AIDS , and nursing interventions can help improve their quality of life . Objectives To test the effects of an intervention based on developing cognitive coping skills as compared to one focused on facilitating the expression of emotions . Both interventions were intended to help regulate emotional response to an exacerbation of HIV-related symptoms . Method In a r and omized , controlled trial , 90 hospitalized HIV-positive men were r and omly assigned to one of three groups : cognitive , expression , or control . The intervention was administered on three consecutive days in 20–30 minute sessions . Preintervention and postintervention data were gathered on mood , distress , and anxiety . Results Both interventions produced a beneficial effect on negative affect ( cognitive group p = .002 , expression group p = .011 ) , and immediately following the first daily session ( p = .001 ) . No change in positive affect was produced by either intervention . Paired t tests indicated a decrease in distress ( p = .039 ) , specifically , of intrusive ideation ( p = .03 ) , for the cognitive group , which also experienced a decrease in anxiety from immediately before to immediately after each session . Conversely , the expression group experienced an increase in anxiety ( p = .018 ) . Discussion The cognitive coping skills nursing intervention was effective in helping to regulate HIV-positive persons ’ emotional responses to advanced disease . This nursing intervention is feasible for use by skilled practitioners providing daily care We examined the efficacy of a psycho-spiritual intervention of mantram repetition -- a word or phrase with spiritual associations repeated silently throughout the day -- on psychological distress ( intrusive thoughts , stress , anxiety , anger , depression ) , quality of life enjoyment and satisfaction , and existential spiritual well-being in HIV-infected adults . Using a 2-group by 4-time repeated measures design , 93 participants were r and omly assigned to mantram ( n = 46 ) or attention control group ( n = 47 ) . Over time , the mantram group improved significantly more than the control group in reducing trait-anger and increasing spiritual faith and spiritual connectedness . Actual mantram practice measured by wrist counters was inversely associated with non-HIV related intrusive thoughts and positively associated with quality of life , total existential spiritual well-being , meaning/peace , and spiritual faith . Intent-to-treat findings suggest that a mantram group intervention and actual mantram practice each make unique contributions for managing psychological distress and enhancing existential spiritual well-being in adults living with HIV/AIDS Objective : To determine the impact of nutritional ( selenium ) chemo-prevention on levels of psychological burden ( anxiety , depression , and mood state ) in HIV/AIDS . Method : A r and omized , double-blind , placebo-controlled selenium therapy ( 200 μ/day ) trial was conducted in HIV+ drug users from 1998–2000 . Psychosocial measures ( STAI-State and Trait anxiety , BDI-depression , and POMS- mood state ) , clinical status ( CD4 cell count , viral load ) , and plasma selenium levels were determined at baseline and compared with measurements obtained at the 12-month evaluation in 63 participants ( 32 men , 31 women ) . Results : The majority of the study participants reported elevated levels of both State ( 68 % ) and Trait ( 70 % ) anxiety . Approximately 25 % reported overall mood distress ( POMS > 60 ) and moderate depression ( BDI > 20 ) . Psychological burden was not influenced by current drug use , antiretroviral treatment , or viral load . At the 12-month evaluation , participants who received selenium reported increased vigor ( p = 0.004 ) and had less anxiety ( State , p = 0.05 and Trait , p = 0.02 ) , compared to the placebo-treated individuals . No apparent selenium-related affect on depression or distress was observed . The risk for state anxiety was almost four times higher , and nearly nine times greater for trait anxiety in the placebo-treated group , controlling for antiretroviral therapy , CD4 cell decline ( > 50 cells ) and years of education . Conclusions : Selenium therapy may be a beneficial treatment to decrease anxiety in HIV+ drug users who exhibit a high prevalence of psychological burden Psychological effects of participation in Protocol 019 , a zidovudine placebo-controlled clinical trial , were investigated . Forty-six Protocol 019 subjects and 27 control asymptomatic human immunodeficiency virus-seropositive subjects were assessed at entry , 2 months , 6 months , and after trial modification . At baseline there were no psychological differences . Most Protocol 019 and control subjects were depressed on at least one psychological measure ; fewer were anxious . Both groups had improvement over time . By 6 months , Protocol 019 subjects had decreased Beck Depression Inventory ( BDI ) scores , state anxiety , stress reaction , and symptoms of depression and anxiety . Controls had decreased scores on only the BDI . Over time , the percentage meeting modified DSM III-R criteria for anxiety decreased in both groups and the proportion of Protocol 019 subjects meeting DSM III-R depression criteria decreased . After protocol modification , study subjects were less depressed and distressed than controls . Protocol 019 subjects reduced depression symptoms but controls did not . Clinical trial participation was not deleterious and may have yielded some relative psychological benefit & NA ; We investigated the effects of two behavioral interventions —aerobic exercise and cognitive behavioral stress management (CBSM)—on Epstein‐Barr virus viral capsid antigen ( EBV‐VCA ) and human herpesvirus type‐6 ( HHV‐6 ) antibody modulation in 65 asymptomatic gay men measured at several time points in the 5 weeks preceding and following notification of their human immunodeficiency virus‐type 1 ( HIV‐1 ) serostatus . After accounting for potential immunomodulatory confounds , we found that HIV‐1 seropositive men had higher EBV‐VCA antibody titers than those diagnosed as seronegative at every time point during the study ; however , no significant differences were found with respect to HHV‐6 . Among HIV‐1 seropositive and seronegative subjects , respectively , those r and omized to either behavioral intervention had significant decreases in both EBV‐VCA and HHV‐6 antibody titers over the course of the intervention as compared with assessment ‐only controls ( of HIV‐1 seropositive and seronegative status ) whose antibody titers did not significantly change and which remained consistently higher than either serostatus‐matched intervention group over subsequent time points , independent of total immunoglobulin G levels and degree of polyclonal B cell activation . In attempting to explain serostatus differences in EBV and HHV‐6 values , it was found that HIV‐1 seropositive men had significantly lower CD4 cells , CD4:CD8 ratio , and blastogenic response to phytohemagglutinin ( PHA ) , as well as significantly higher CD8 cells at baseline . No significant differences were found between the HIV‐1 seropositive and seronegative men with respect to anxiety and depression at baseline . Since the greatest changes in EBV and HHV‐6 occurred between baseline and week 10 , we correlated changes in immune ( CD4 , CD8 , CD4:CD8 ratio , PHA stimulation ) and distress‐related markers ( state depression and anxiety ) with EBV and HHV‐6 change scores over this time period . No significant correlations were found between any of these immune‐ or distress‐related variable and the antibody change scores suggesting that the mechanisms by which EBV and HHV‐6 antibodies are being modulated by these interventions possibly involve other , yet to be determined , immune , neuroendocrine , and /or psychologic variables Objective : To evaluate the safety and efficacy of polyalkylimide gel ( PAIG ) in the treatment of HIV-associated facial lipoatrophy . Design : A r and omized , open-label , single-centre study . Methods : HIV-positive individuals with facial lipoatrophy ( based on physician assessment ) were r and omly assigned to immediate Output:	Psychological interventions ( especially cognitive behavioural stress management interventions and cognitive behavioural therapy ) were generally more effective than pharmacological interventions . Our detailed data suggest that interventions are both effective and available , although further research into enhancing efficacy would be valuable .
MS21355	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Diabetes self-management education interventions in community gathering places have been moderately effective , but very few studies of intervention effectiveness have been conducted among African Americans with type 2 diabetes . This paper describes a church-based diabetes self-management education intervention for African Americans , a r and omized controlled trial to evaluate the intervention , and baseline characteristics of study participants . Methods A New DAWN : Diabetes Awareness & Wellness Network was conducted among 24 churches of varying size in North Carolina . Each church recruited congregants with type 2 diabetes and design ated a diabetes advisor , or peer counselor , to be part of the intervention team . Participants were enrolled at each church and r and omized as a unit to either the special intervention or the minimal intervention . The special intervention included one individual counseling visit , twelve group sessions , three postcard messages from the participant 's diabetes care provider , and twelve monthly telephone calls from a diabetes advisor . Baseline data included measures of weight , hemoglobin A1c , blood pressure , physical activity , dietary and diabetes self-care practice s , and psychosocial factors . The study to evaluate the intervention ( from enrollment visit to last follow-up ) began in February 2001 and ended in August 2003 . Results Twenty-four churches ( with 201 total participants ) were r and omized . Sixty-four percent of the participants were women . On average , the participants were aged 59 years and sedentary . They had an average of 12 years of education , had been diagnosed with diabetes for 9 years , had a body mass index of 35 , had a hemoglobin A1c level of 7.8 % , and had a reported dietary intake of 39 % of calories from fat . Conclusion A New DAWN is a culturally sensitive , church-based diabetes self-management education program for African Americans with type 2 diabetes that is being evaluated for effectiveness in a r and omized controlled trial . The outcomes of A New DAWN will contribute to the literature on community-based interventions for minority population s and help to inform the selection of approaches to improve diabetes care in this population Existing st and ards of the management of the diabetic patients are not efficient enough , and further improvement is needed . The major objective of this paper is to present and discuss the therapeutic effectiveness of an intensive care telematic system design ed and applied for intensive treatment of pregnant type 1 diabetic women . The developed system operates automatically , every night transferring all the data recorded during the day in the patient 's glucometer memory to a central clinical unit . In order to assess the efficiency of the design ed and developed system , a 3-year r and omized prospect i ve clinical trial was conducted , using the study group and the control group , each consisting of 15 pregnant type 1 diabetic women . All patients were treated by the same diabetologist . In the presented analysis , two indices calculated weekly were used for the assessment of glycemic control : MBG represents mean blood glucose level , and the universal J-index is sensitive to the glycemic level and glycemic variations . The most important results from the study concern : ( a ) better glycemic control in the study group in comparison with the control group during the course of treatment , as assessed by the average differences of the MBG and J indices calculated weekly ( n = 24 ) ( deltaMBG = -3.2 + /- 4.3 mg/dL , p = 0.0016 , deltaJ = -1.4 + /- 2.3 , p = 0.0065 ) ; ( b ) much more similar results in glycemic control among members of the study group compared to each other , than among members of the control group compared to each other , as indicated by significantly lower variations of the applied glycemic control indices ( SDMBG : 11.9 vs. 18.7 mg/dL , p = 0.0498 ; SDJ : 6.5 vs. 10.9 , p = 0.0318 ) ; ( c ) the observed tendency of a better glycemic control for patients with a lower level of intelligence ( IQ < 100 ) supported by the telematic system in comparison with all other assessed groups of patients . The last result was not statistically significant ( p > 0.05 ) . This telematic intensive care system improved the effectiveness of diabetes treatment during pregnancy . It also allows the diabetologist 's strategy to be much more precise than if it were conducted without telematic support . This telematic system is inexpensive and simple in use CONTEXT Level of acuity and number of referrals for home health care have been escalating exponentially . As referrals continue to increase , health care organizations are encouraged to find more effective methods for providing high- quality patient care with cost savings . OBJECTIVE To evaluate the use of remote video technology in the home health care setting as well as the quality , use , patient satisfaction , and cost savings from this technology . DESIGN Quasi-experimental study conducted from May 1996 to October 1997 . SETTING Home health department in the Sacramento , Calif , facility of a large health maintenance organization . PARTICIPANTS Newly referred patients diagnosed as having congestive heart failure , chronic obstructive pulmonary disease , cerebral vascular accident , cancer , diabetes , anxiety , or need for wound care were eligible for r and om assignment to intervention ( n = 102 ) or control ( n = 110 ) groups . INTERVENTION The control and intervention groups received routine home health care ( home visits and telephone contact ) . The intervention group also had access to a remote video system that allowed nurses and patients to interact in real time . The video system included peripheral equipment for assessing cardiopulmonary status . MAIN OUTCOME MEASURES Three quality indicators ( medication compliance , knowledge of disease , and ability for self-care ) ; extent of use of services ; degree of patient satisfaction as reported on a 3-part scale ; and direct and indirect costs of using the remote video technology . RESULTS No differences in the quality indicators , patient satisfaction , or use were seen . Although the average direct cost for home health services was $ 1830 in the intervention group and $ 1167 in the control group , the total mean costs of care , excluding home health care costs , were $ 1948 in the intervention group and $ 2674 in the control group . CONCLUSIONS Remote video technology in the home health care setting was shown to be effective , well received by patients , capable of maintaining quality of care , and to have the potential for cost savings . Patients seemed pleased with the equipment and the ability to access a home health care provider 24 hours a day . Remote technology has the potential to effect cost savings when used to substitute some in-person visits and can also improve access to home health care staff for patients and caregivers . This technology can thus be an asset for patients and providers OBJECTIVE The study 's objective was to assess the effects of automated telephone outreach with speech recognition ( ATO-SR ) on diabetes-related testing . RESEARCH DESIGN AND METHODS We identified 1,200 health plan members who were overdue for diabetes-related testing and r and omly allocated 600 to ATO-SR and 600 to usual care ( no intervention ) . The intervention included three interactive calls encouraging recommended testing . The primary outcome was retinopathy testing , since this was the health plan 's principal goal . Tests for glycemia , hyperlipidemia , and nephropathy were secondary outcomes . RESULTS In total , 232 participants ( 39 % ) verbally responded to the calls . There was no difference between the intervention and the usual care groups in the primary outcome ( adjusted hazard ratio 0.93 [ 95 % CI 0.71–1.22 ] ) and no effect of the intervention on any of the secondary outcomes . CONCLUSIONS Fewer than 40 % of the patients r and omized to ATO-SR interacted verbally with the system . The intervention had no effect on the study 's outcomes OBJECTIVE To report results from YourWay , an Internet-based self-management intervention for adolescents with type 1 diabetes . RESEARCH DESIGN AND METHODS A total of 72 adolescents with type 1 diabetes , ages 13–17 years , were r and omized to a usual-care-plus-Internet support or a usual-care group . The intervention was design ed to enhance problem-solving barriers to self-management . A1C was obtained from medical records , and problem-solving and self-management were obtained via adolescent report . RESULTS Group differences were not statistically significant using intent-to-treat analyses . Using as-treated analyses , adolescents in the treatment condition showed statistically significant improvement in self-management ( d = 0.64 ; P = 0.02 ) and important improvements in problem-solving ( d = 0.30 ; P = 0.23 ) and A1C ( d = −0.28 ; P = 0.27 ) . Mean A1C for the intervention group remained constant ( −0.01 % ) , while the control group increased ( 0.33 % ) . CONCLUSIONS This brief trial suggests that self-management support delivered through a secure website may improve self-management and offset typical decreases in adolescent glycemic control OBJECTIVE We evaluated automated telephone disease management ( ATDM ) with telephone nurse follow-up as a strategy for improving diabetes treatment processes and outcomes in Department of Veterans Affairs ( VA ) clinics . We also compared the results with those of a prior ATDM trial conducted in a county health care system . RESEARCH DESIGN AND METHODS A total of 272 VA patients with diabetes using hypoglycemic medications were r and omized . During the 1-year study period , intervention patients received biweekly ATDM health assessment and self-care education calls , and a nurse educator followed up with patients based on their ATDM assessment reports . Telephone surveys were used to measure patients ' self-care , symptoms , and satisfaction with care . Outpatient service use was evaluated using electronic data bases and self-reports , and glycemic control was measured by HbA1c and serum glucose testing . RESULTS At 12 months , intervention patients reported more frequent glucose self-monitoring and foot inspections than patients receiving usual care and were more likely to be seen in podiatry and diabetes specialty clinics . Intervention patients also were more likely than control patients to have had a cholesterol test . Among patients with baseline HbA1c levels > or = 8 % , mean end-point values were lower among intervention patients than control patients ( 8.7 vs. 9.2 % , respectively ; P = 0.04 ) . Among intervention and control patients with baseline values > or = 9 % , mean end-point values were 9.1 and 10.2 % , respectively ( P = 0.04 ) . At follow-up , intervention patients reported fewer symptoms of poor glycemic control than control patients and greater satisfaction with their health care . CONCLUSIONS This intervention improved the quality of VA diabetes care . Intervention effects for most end points replicated findings from the prior county clinic trial , although intervention-control differences in the current study were smaller because of the relatively good self-care and health status among the current study 's enrollees OBJECTIVE Internet and other interactive technology-based programs offer great potential for practical , effective , and cost-efficient diabetes self-management ( DSM ) programs capable of reaching large numbers of patients . This study evaluated minimal and moderate support versions of an Internet-based diabetes self-management program , compared to an enhanced usual care condition . RESEARCH DESIGN AND METHODS A three-arm practical r and omized trial was conducted to evaluate minimal contact and moderate contact versions of an Internet-based diabetes self-management program , offered in English and Spanish , compared to enhanced usual care . A heterogeneous sample of 463 type 2 patients was r and omized and 82.5 % completed a 4-month follow-up . Primary outcomes were behavior changes in healthy eating , physical activity , and medication taking . Secondary outcomes included hemoglobin A1c , body mass index , lipids , and blood pressure . RESULTS The Internet-based intervention produced significantly greater improvements than the enhanced usual care condition on three of four behavioral outcomes ( effect sizes [ d ] for healthy eating = 0.32 ; fat intake = 0.28 ; physical activity= 0.19 ) in both intent-to-treat and complete-cases analyses . These changes did not translate into differential improvements in biological outcomes during the 4-month study period . Added contact did not further enhance outcomes beyond the minimal contact intervention . CONCLUSIONS The Internet intervention meets several of the RE- AIM criteria for potential public health impact , including reaching a large number of persons , and being practical , feasible , and engaging for participants , but with mixed effectiveness in improving outcomes , and consistent results across different subgroups . Additional research is needed to evaluate longer-term outcomes , enhance effectiveness and cost-effectiveness , and underst and the linkages between intervention processes and outcomes OBJECTIVE We evaluated the impact of automated telephone disease management ( ATDM ) calls with telephone nurse follow-up as a strategy for improving outcomes such as mental health , self-efficacy , satisfaction with care , and health-related quality of life ( HRQL ) among low-income patients with diabetes mellitus . RESEARCH DESIGN This was a r and omized , controlled trial . SUBJECTS Two hundred forty-eight primarily English- and Spanish-speaking adults with diabetes enrolled at the time of visits to a county health care system . INTERVENTION In addition to usual care , intervention patients received biweekly ATDM calls with telephone follow-up by a diabetes nurse educator . Patients used the ATDM calls to report information about their health and self-care and to access self-care education . The nurse used patients ' ATDM reports to allocate her time according to their needs . MEASURES Patient-centered outcomes were measured at 12 months via telephone interview . RESULTS Compared with patients receiving usual care , intervention patients at follow-up reported fewer symptoms of depression ( P = 0.023 ) , greater Output:	Nevertheless , it would probably not change the overall conclusion of the review , that “ telemedicine is a promising alternative to conventional therapy ” and that “ behavioural therapy enhanced by telemonitoring appears to be the most suitable mode of intervention ”
MS21356	*TASK* the task is to summarize an input biomedical literature in six sentences *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 was design ed to evaluate the effect of combining fractional CO2 laser with narrow-b and ultraviolet B ( NB-UVB ) versus NB-UVB in the treatment of non-segmental vitiligo . The study included 20 patients with non-segmental stable vitiligo . They were divided into two groups . Group I received a single session of fractional CO2 laser therapy on the right side of the body followed by NB-UVB phototherapy twice per week for 8 weeks . Group II received a second session of fractional CO2 laser therapy after 4 weeks from starting treatment with NB-UVB . The vitiligo lesions were assessed before treatment and after 8 weeks of treatment by VASI . At the end of the study period , the vitiligo area score index ( VASI ) in group I decreased insignificantly on both the right ( −2.6 % ) and left ( −16.4 % ) sides . In group II , VASI increased insignificantly on the right ( + 14.4 % ) and left ( + 2.5 % ) sides . Using Adobe Photoshop CS6 extended program to measure the area of vitiligo lesions , group I showed a decrease of −1.02 and −6.12 % in the mean area percentage change of vitiligo lesions on the right and left sides , respectively . In group II the change was + 9.84 and + 9.13 % on the right and left sides , respectively . In conclusion , combining fractional CO2 laser with NB-UVB for the treatment of non-segmental vitiligo did not show any significant advantage over treatment with NB-UVB alone . Further study of this combination for longer duration s in the treatment of vitiligo is recommended Resistant non-segmental vitiligo is difficult to be treated . Ablative erbium-YAG ( Er : YAG ) laser has been used in the treatment of vitiligo , but the ablation of entire epidermis frustrated the compliance of patients . The purpose of this study is to investigate the effects of fractional Er : YAG laser followed by topical betamethasone and narrow b and ultraviolet B ( NB-UVB ) therapy in the treatment of resistant non-segmental vitiligo . The vitiligo lesions of each enrolled patient were divided into four treatment parts , which were all irradiated with NB-UVB . Three parts were , respectively , treated with low , medium , or high energy of Er : YAG laser , followed by topical betamethasone solution application . A control part was spared with laser treatment and topical betamethasone . The treatment period lasted 6 months . The efficacy was assessed by two blinded dermatologists . Treatment protocol with high energy of 1800 mJ/P of fractional Er : YAG laser followed by topical betamethasone solution and in combination with NB-UVB made 60 % patients achieve marked to excellent improvement in white patches . The protocol with medium energy of 1200 mJ/P of laser assisted approximate 36 % patients achieve such improvement . The two protocol s , respectively , showed better efficacies than NB-UVB only protocol . However , fractional Er : YAG laser at low energy of 600 mJ/P did not provide such contributions to the treatment of vitiligo . The fractional Er : YAG laser in combination with topical betamethasone solution and NB-UVB was suitable for resistant non-segmental vitiligo . The energy of laser was preferred to be set at relatively high level BACKGROUND Vitiligo is a pigmentary disorder of skin affecting at least 1 % of the world population of all races in both sexes . Its importance is mainly due to subsequent social and psychological problems rather than clinical complications . Various treatment choices are available for vitiligo ; however , laser-based courses have shown to give more acceptable results . OBJECTIVE The aim of this trial was to evaluate the efficacy of Er : YAG laser as a supplementary medicine to topical 5FU and clobetasol in vitiligo patients . METHODS Two comparable vitiligo patches from 38 eligible patients were r and omized to receive topical 5FU and clobetasol in control group and additional Er : YAG laser in intervention group . Major outcomes of interest were the size of patch and pigmentation score at r and omization and 2 and 4 months after therapy . RESULTS Final sample included 18 ( 47 % ) male patients and age of 35.66±8.04 . The performance Er : YAG group was superior in all sites . Reduction in the size of patches was greater in Er : YAG group ( p-value=.004 ) . Also , this group showed a higher pigmentation scores in the trial period than control group ( p-value<.001 ) . CONCLUSIONS Greater reduction in the size and increase in pigmentation score was seen in Er : YAG group especially for short periods after therapy and repeating laser sessions may help improving final outcomes . Er : AYG could help in reducing complications of long-term topical treatments , achieving faster response , and improving patient adherence Facial vitiligo is associated with considerable psychological impact . The management is challenging and requires multidisciplinary treatment . Adding fractional carbon dioxide ( CO2 ) to the conventional treatment has been reported as an effective modality . This study aim ed to evaluate the efficacy of combined fractional CO2 laser , targeted ultraviolet B ( UVB ) phototherapy , and topical steroid on facial vitiligo . A prospect i ve , r and omized , split face study was conducted on 14 patients with symmetrical non-segmental facial vitiligo . Ten sessions of fractional CO2 laser was performed on the lesions on one side of face with 2-week interval . Immediately after laser , the lesions on both side of face were treated with 10 sessions of 2-week interval targeted UVB phototherapy and twice daily application of topical 0.05 % clobetasol propionate cream . The patients were followed up for 12 weeks after the last treatment . Clinical improvement was grade d by blinded dermatologists and patients using a quartile grading scale . Twelve out of 14 patients completed the study . The degree of improvement was not different between both sides in nine patients . One patient showed more improvement on the combined laser side , and two patients showed inferior results on the combined laser side . Two patients with lesser improvement on the laser-treated side had positive Koebner phenomenon on the non-facial area . The combined treatment with laser , targeted UVB , and topical steroids are not superior to targeted UVB and topical steroids in facial vitiligo . Furthermore , laser may retard the response to the st and ard treatment in patients with Koebner phenomenon on non-treated areas Despite the multiple treatment modalities available for vitiligo , none of them gives satisfactory results in the periungual type . In this study we tried to explore and evaluate the effects of the combination treatment of erbium : YAG laser resurfacing and topical 5-flurouracil in periungual vitiligo . Nine adult patients presenting with periungual vitiligo lesions were included in this prospect i ve left-right comparative study . The desirable inflammation was achieved after a mean of 4.7 days of 5-flurouracil application . The mean re-epithelization time in the treatment sessions was 11.3 days . The patients received a mean of 3.4 sessions in a mean duration of 7.6 months . The mean overall response to therapy in the treated group was 47.8 % while in the control group it was 1.1 % ( P < 0.0001 ) . No side effects necessitated the stoppage of treatment . This study points to the efficacy and safety of this combination in the treatment of periungual vitiligo BACKGROUND Fractional CO2 laser and autologous hair transplantation are independently effective in the treatment of refractory and stable vitiligo . OBJECTIVE The authors ' purpose was to evaluate the therapeutic efficacy of fractional CO2 laser pretreatment compared with autologous hair transplantation and phototherapy alone for refractory and stable vitiligo . METHODS A total of 20 patients with refractory and stable vitiligo were enrolled from our clinic . Resistant lesions r and omly divided into 2 regions as follows : ( 1 ) Part A : fractional CO2 laser pretreatment followed by autologous transplantation and phototherapy , and ( 2 ) Part B : autologous transplantation and phototherapy alone . Five days after fractional CO2 laser application to Part A , both treatment regions received a transplant of scalp grafts . On Day 11 , the entire lesion was exposed to narrow-b and UVB phototherapy , twice a week for 12 weeks . The diameter of perifollicular repigmentation was measured monthly with a caliper . RESULTS Perifollicular repigmentation was detectable surrounding 74 % of grafted hair follicles by Month 3 . Furthermore , Part A demonstrated a significantly greater diameter of repigmentation with 6.6 ± 5.8 mm in Part A compared with 4.3 ± 1.8 mm in Part B ( p = < .001 ) . CONCLUSION In this study , our results demonstrate improved efficacy of autologous hair transplantation and narrow-b and UVB with fractional CO2 laser pretreatment in refractory and stable vitiligo OBJECTIVE To compare the efficacy and safety of using a combination of fluticasone propionate ( FP ) and UV-A with that of either drug used alone in the long-term treatment of vitiligo . DESIGN Prospect i ve , r and omized , controlled , left-right comparison study . Repigmentation was judged by a single dermatologist ( L.N.-K. ) and skin thickness was scored by a pathologist ( using biopsy sample s ) , a dermatologist ( L.N.-K. ) ( visually ) , and patients ( using a st and ard question naire ) . SETTING Netherl and s Institute for Pigmentary Disorders , Amsterdam . PATIENTS Patients with lesions on arms , legs , and trunk were treated on 2 symmetrical lesions for 9 months with FP alone and a combination of FP and UV-A ( FP group ) or with UV-A alone and a combination of FP and UV-A ( UV-A group ) . Fluticasone propionate cream was applied once daily at about bedtime , and UV-A ( 10 J/cm2 ) exposure was twice a week . Patients attended the clinic at 3-month intervals . RESULTS One hundred thirty-five patients were included , 96 of whom were evaluable after 9 months . Patients not reaching the end point withdrew because of insufficient repigmentation ( n = 23 ) , decreased motivation ( n = 11 ) , or protocol violations ( n = 5 ) . No patient ( irrespective of whether they withdrew ) experienced any adverse effects . The FP and UV-A groups were comparable with respect to sex , age , and location of lesions . On average , combination treatment was 3 times more effective than either UV-A or FP treatment alone . In the FP group , no atrophy was seen after 9 months with either treatment . In the UV-A group , a little atrophy was detected twice : as well during UV-A treatment alone as during combination treatment . CONCLUSIONS Combination treatment with FP and UV-A is much more effective in reaching complete repigmentation than are FP and UV-A used alone , but large inter-individual differences occur . Fluticasone propionate , UV-A , and a combination of FP and UV-A seem to be safe for long-term treatment of vitiligo BACKGROUND AND OBJECTIVE Conventional treatment of vitiligo on h and s and feet often produces an unsatisfactory result . Various ablative treatment methods were tried with favorable results in facial , neck , and truncal areas . The aim of this study is to evaluate the efficacy and safety of combined fractional CO2 laser , narrowb and UVB ( NB-UVB ) phototherapy , and topical clobetasol propionate in managing stable vitiligo in difficult-to-treat areas . STUDY DESIGN A prospect i ve r and omized-intraindividual study was conducted on 27 patients with 27 pair-lesions of non-segmental vitiligo on both h and s. The lesions were r and omized to receive treatment with fractional CO2 laser , NB-UVB phototherapy , and 0.05 % clobetasol propionate cream ( Group A ) or NB-UVB phototherapy and 0.05 % clobetasol propionate cream ( Group B ) . Fractional CO2 laser was performed at 1-week interval for 10 sessions . NB-UVB phototherapy was administered twice weekly for 20 sessions . Patients were evaluated 12 weeks after the last treatment . Outcome was evaluated objective ly based on st and ard digital photographs , patient satisfaction , and adverse events . RESULTS Twenty-six patients completed the study . Six vitiligious lesions ( 23.1 % ) in group A achieved good to excellent repigmentation compared with one lesion ( 3.9 % ) in group B ( P = 0.065 ) . The overall mean improvement score was 1.35 ( ± 1.38 ) in group A and 0.50 ( ± 0.95 ) in group B ( P = 0.0004 ) . Patients ' satisfaction score was significantly higher for the lesions in group A than group B. Lesions on the dorsum of the h and showed a higher response rate than those on the fingers . No serious side-effects were noted . CONCLUSION This study demonstrates that adding fractional CO2 laser treatment to NB-UVB phototherapy and topical steroids improves the repigmentation rate of vitiliginous lesions on h and s in some patients . This technique may be offered to vitiligo patients who are unresponsive to other treatments The aim of this study is to evaluate the use of fractional carbon dioxide laser ( CO2 ) with betamethasone and salicylic acid solution in the treatment of patients with refractory vitiligo in h and s. Each h and of the patient was r and omly assigned to one of Output:	Subgroup analysis showed that the erbium laser group , CO2 laser group and fractional CO2 laser group achieved significantly better repigmentation than the control groups . According to objective and subjective evaluations , treatments for vitiligo are more effective when combined with ablation therapy than when used alone
MS21357	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Tofacitinib is an oral Janus kinase ( JAK ) inhibitor for the treatment of rheumatoid arthritis ( RA ) . The pathways affected by tofacitinib and the effects on gene expression in situ are unknown . Therefore , tofacitinib effects on synovial pathobiology were investigated . Methods A r and omised , double-blind , phase II serial synovial biopsy study ( A3921073 ; NCT00976599 ) in patients with RA with an inadequate methotrexate response . Patients on background methotrexate received tofacitinib 10 mg twice daily or placebo for 28 days . Synovial biopsies were performed on Days -7 and 28 and analysed by immunoassay or quantitative PCR . Clinical response was determined by disease activity score and European League Against Rheumatism ( EULAR ) response on Day 28 in A3921073 , and at Month 3 in a long-term extension study ( A3921024 ; NCT00413699 ) . Results Tofacitinib exposure led to EULAR moderate to good responses ( 11/14 patients ) , while placebo was ineffective ( 1/14 patients ) on Day 28 . Tofacitinib treatment significantly reduced synovial mRNA expression of matrix metalloproteinase (MMP)-1 and MMP-3 ( p<0.05 ) and chemokines CCL2 , CXCL10 and CXCL13 ( p<0.05 ) . No overall changes were observed in synovial inflammation score or the presence of T cells , B cells or macrophages . Changes in synovial phosphorylation of signal transducer and activator of transcription 1 ( STAT1 ) and STAT3 strongly correlated with 4-month clinical responses ( p<0.002 ) . Tofacitinib significantly decreased plasma CXCL10 ( p<0.005 ) at Day 28 compared with placebo . Conclusions Tofacitinib reduces metalloproteinase and interferon-regulated gene expression in rheumatoid synovium , and clinical improvement correlates with reductions in STAT1 and STAT3 phosphorylation . JAK1-mediated interferon and interleukin-6 signalling likely play a key role in the synovial response . Trial registration number NCT00976599 Introduction Rheumatoid arthritis ( RA ) is a complex and clinical ly heterogeneous autoimmune disease . Currently , the relationship between pathogenic molecular drivers of disease in RA and therapeutic response is poorly understood . Methods We analyzed synovial tissue sample s from two RA cohorts of 49 and 20 patients using a combination of global gene expression , histologic and cellular analyses , and analysis of gene expression data from two further publicly available RA cohorts . To identify c and i date serum biomarkers that correspond to differential synovial biology and clinical response to targeted therapies , we performed pre-treatment biomarker analysis compared with therapeutic outcome at week 24 in serum sample s from 198 patients from the ADACTA ( ADalimumab ACTemrA ) phase 4 trial of tocilizumab ( anti-IL-6R ) monotherapy versus adalimumab ( anti-TNFα ) monotherapy . Results We documented evidence for four major phenotypes of RA synovium – lymphoid , myeloid , low inflammatory , and fibroid - each with distinct underlying gene expression signatures . We observed that baseline synovial myeloid , but not lymphoid , gene signature expression was higher in patients with good compared with poor European league against rheumatism ( EULAR ) clinical response to anti-TNFα therapy at week 16 ( P = 0.011 ) . We observed that high baseline serum soluble intercellular adhesion molecule 1 ( sICAM1 ) , associated with the myeloid phenotype , and high serum C-X-C motif chemokine 13 ( CXCL13 ) , associated with the lymphoid phenotype , had differential relationships with clinical response to anti-TNFα compared with anti-IL6R treatment . sICAM1-high/CXCL13-low patients showed the highest week 24 American College of Rheumatology ( ACR ) 50 response rate to anti-TNFα treatment as compared with sICAM1-low/CXCL13-high patients ( 42 % versus 13 % , respectively , P = 0.05 ) while anti-IL-6R patients showed the opposite relationship with these biomarker subgroups ( ACR50 20 % versus 69 % , P = 0.004 ) . Conclusions These data demonstrate that underlying molecular and cellular heterogeneity in RA impacts clinical outcome to therapies targeting different biological pathways , with patients with the myeloid phenotype exhibiting the most robust response to anti-TNFα . These data suggest a path to identify and vali date serum biomarkers that predict response to targeted therapies in rheumatoid arthritis and possibly other autoimmune diseases . Trial registration Clinical Trials.gov BACKGROUND Effective new therapies are needed for rheumatoid arthritis . Current therapies target the products of activated macrophages ; however , T cells also have an important role in rheumatoid arthritis . A fusion protein -- cytotoxic T-lymphocyte-associated antigen 4-IgG1 (CTLA4Ig)--is the first in a new class of drugs known as costimulation blockers being evaluated for the treatment of rheumatoid arthritis . CTLA4Ig binds to CD80 and CD86 on antigen-presenting cells , blocking the engagement of CD28 on T cells and preventing T-cell activation . A preliminary study showed that CTLA4Ig may be effective for the treatment of rheumatoid arthritis . METHODS We r and omly assigned patients with active rheumatoid arthritis despite methotrexate therapy to receive 2 mg of CTLA4Ig per kilogram of body weight ( 105 patients ) , 10 mg of CTLA4Ig per kilogram ( 115 patients ) , or placebo ( 119 patients ) for six months . All patients also received methotrexate therapy during the study . The clinical response was assessed at six months with use of the criteria of the American College of Rheumatology ( ACR ) , which define the response according to its extent : 20 percent ( ACR 20 ) , 50 percent ( ACR 50 ) , or 70 percent ( ACR 70 ) . Additional end points included measures of the health-related quality of life . RESULTS Patients treated with 10 mg of CTLA4Ig per kilogram were more likely to have an ACR 20 than were patients who received placebo ( 60 percent vs. 35 percent , P<0.001 ) . Significantly higher rates of ACR 50 and ACR 70 responses were seen in both CTLA4Ig groups than in the placebo group . The group given 10 mg of CTLA4Ig per kilogram had clinical ly meaningful and statistically significant improvements in all eight subscales of the Medical Outcomes 36-Item Short-Form General Health Survey . CTLA4Ig was well tolerated , with an overall safety profile similar to that of placebo . CONCLUSIONS In patients with active rheumatoid arthritis who were receiving methotrexate , treatment with CTLA4Ig significantly improved the signs and symptoms of rheumatoid arthritis and the health-related quality of life . CTLA4Ig is a promising new therapy for rheumatoid arthritis Objective Despite the fact that rituximab depletes B cells in all treated patients with RA , not all patients show a favourable clinical response . The goal of this study was to provide insight into pharmacological changes in peripheral blood that are associated with clinical response to rituximab . Methods Gene expression profiling was performed on peripheral blood RNA of 13 patients with RA ( test group ) using Illumina HumanHT beadchip microarrays . An independent group of nine patients was used for validation using TaqMan quantitative PCR . Clinical responder status was determined after 6 months using change in 28-joint Disease Activity Score ( ΔDAS28 ) and European League Against Rheumatism ( EULAR ) response criteria . Significance analysis of microarrays and ontology analysis were used for data analysis and interpretation . Results Pharmacogenomic analyses demonstrated marked interindividual differences in the pharmacological responses at 3 and 6 months after start of treatment with rituximab . Interestingly , only differences in the regulation of type I interferon (IFN)-response genes after 3 months correlated with the ΔDAS28 response . Good responders ( ∆DAS>1.2 ; n=7 ) exhibited a selective increase in the expression of type I IFN-response genes , whereas this activity was unchanged or hardly changed in non-responders ( ∆DAS<1.2 ; n=6 ) ( p=0.0040 at a cut-off of 1.1-fold induction ) . Similar results were obtained using EULAR response criteria . These results were vali date d in an independent cohort of nine patients ( five non-responders and four responders , p=0.0317 ) . Conclusions A good clinical response to rituximab in RA is associated with a selective drug-induced increase in type I IFN-response activity in patients with RA . This finding may provide insight in the biological mechanism underlying the therapeutic response to rituximab The aim of this prospect i ve multicenter study was to identify biomarkers that can be used to predict therapeutic responses to tocilizumab in patients with rheumatoid arthritis ( RA ) Output:	Many studies report the association between type I interferon signature gene expression and response to therapy
MS21358	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objective The aim of this prospect i ve , r and omized , clinical study was to assess the effect of photobiomodulation therapy ( PBM ) with low-level laser irradiation ( LLLI ) on postoperative pain after endodontic treatment . Material s and methods Sixty patients , diagnosed with irreversible pulpitis in lower molar teeth , participated in the study . All treatments were performed by a single operator . Participants were r and omly divided into two groups : in the experimental group ( EG ) , endodontic treatment was performed with a reciprocating system , immediately followed by PBM with LLLI ; and only endodontic treatment was performed in the control group ( CG ) . Postoperative pain was assessed by a second examiner , who was blinded , using two scales : verbal rating scale ( VRS ) and numerical rating scale ( NRS ) . Assessment was carried out at 6 , 12 , and 24 h after treatment . Data were analyzed using chi-squared , Fisher ’s exact , Mann-Whitney tests , ordinal , and non-parametric regression analyses . Results For the prevalence of pain , the difference between the groups was significant for the evaluations performed after 6 h ( p = 0.04 ) and 24 h ( p = 0.02 ) . The difference after 24 h remained significant after stratification by sex and extrusion of filling material . Increased pain intensity was associated with extrusion of root canal filling material to the periapical region in the two scales used . Conclusion The effect of PBM therapy after endodontic treatment showed a significant decreasein prevalence of postoperative pain . Clinical relevance The PBM reduces the prevalence of postoperative pain and may benefit patients who need endodontic treatment Introduction : The aim of this r and omized clinical trial was to evaluate the influence of rotary or reciprocating retreatment techniques on the incidence , intensity , duration of postoperative pain , and medication intake . Methods : After power analysis calculations , 65 patients who needed endodontic retreatment were r and omly assigned to 1 of 2 groups according to the instrumentation system used : Mtwo ( VDW , Munich , Germany ) or Reciproc ( VDW ) . Retreatments were performed in a single visit by an endodontic specialist . Participants were asked to rate the incidence and intensity of the postoperative pain on a verbal rating scale 24 , 48 , and 72 hours after treatment . Patients were also asked to record the number of prescribed analgesic medication tablets ( ibuprofen 400 mg ) taken . A logistic regression analysis was used to assess both the incidence and duration of pain . Differences in the intensity of pain were analyzed using the ordinal ( linear ) chi‐square test , and the Mann‐Whitney U test was used to assess differences in the intake of analgesic medication between groups . Results : No statistically significant difference was found among the 2 groups in relation to postoperative pain or analgesic medication intake at the 3 time points assessed ( P > .05 ) . Multivariate analysis showed a significantly higher incidence of pain after 24 hours when preoperative pain was present and a significantly longer duration of pain for men than women independently of the retreatment technique used . Conclusions : The reciprocating system and the continuous rotary system were found to be equivalent regarding the incidence , intensity , duration of postoperative pain , and intake of analgesic medication OBJECTIVES The aim of this prospect i ve study was to investigate the correlation between the intensity of preoperative pain and the presence of postoperative pain , taking into account the variables sex , tooth type , arch , and tooth vitality . METHODS Two hundred and seventy patients with pulpal pathology who were scheduled for routine endodontic treatment were enrolled in this study . Conventional endodontic treatment was carried out in a single visit . The chemomechanical preparation of root canals was performed with ProTaper instruments , and canals were obturated with a warm gutta-percha obturation technique . A structured question naire was used to record data on sex , age , type of tooth , location and pulp diagnosis . Patients were asked to record their preoperative and postoperative pain using a 10-cm visual analogue scale ( VAS ) . Postoperative pain and the need for analgesic consumption were assessed at 4 , 8 , 16 , 24 , 48 and 72h post-treatment . The data were analyzed using the Mann-Whitney U and chi-square test , and the significance was set at P<.05 . RESULTS The mean level of pain after root canal treatment was 2.58±2.80 on a VAS between 0 and 10 . Variables that were associated with a higher preoperative pain intensity ( female , m and ible and molar ) also had a higher value of postoperative pain ( P>.05 ) . CONCLUSIONS Within the limitations of this study , it can be concluded that the presence of preoperative pain is the variable that most influences the prevalence of postoperative pain . CLINICAL SIGNIFICANCE Pain management should be an integral part of dental treatment . The present study analyses the incidence of postoperative pain that should be expected by patients with different intensity of pain before root canal treatment Some patients experience severe pain following root canal therapy ( RCT ) despite advancements in care . We sought to identify factors , which can be measured preoperatively , that predict this negative outcome so that future research may focus on preemptive steps to reduce postoperative pain intensity . Sixty-two practitioners ( 46 general dentists and 16 endodontists ) who are members of the National Dental Practice -Based Research Network enrolled patients receiving RCT for this prospect i ve observational study . Baseline data collected from patients and dentists were obtained before treatment . Severe postoperative pain was defined based on a rating of ≥7 on a scale from 0 ( no pain ) to 10 ( pain as bad as can be ) for the worst pain intensity experienced during the preceding week , and this was collected 1 wk after treatment . Multiple logistic regression analyses were used to develop and vali date the model . A total of 708 patients were enrolled during a 6-m period . Pain intensity data were collected 1 wk postoperatively from 652 patients ( 92.1 % ) , with 19.5 % ( n = 127 ) reporting severe pain . In multivariable modeling , baseline factors predicting severe postoperative pain included current pain intensity ( odds ratio [ OR ] , 1.15 ; 95 % confidence interval [ CI ] , 1.07 to 1.25 ; P = 0.0003 ) , number of days in the past week that the subject was kept from their usual activities due to pain ( OR , 1.32 ; 95 % CI , 1.13 to 1.55 ; P = 0.0005 ) , pain made worse by stress ( OR , 2.55 ; 95 % CI , 1.22 to 5.35 ; P = 0.0130 ) , and a diagnosis of symptomatic apical periodontitis ( OR , 1.63 ; 95 % CI , 1.01 to 2.64 ; P = 0.0452 ) . Among the factors that did not contribute to predicting severe postoperative pain were the dentist ’s specialty training , the patient ’s age and sex , the type of tooth , the presence of swelling , or other pulpal and apical endodontic diagnoses . Factors measured preoperatively were found to predict severe postoperative pain following RCT . Practitioners could use this information to better inform patients about RCT outcomes and possibly use different treatment strategies to manage their patients ( Clinical trials.gov NCT01201681 ) BACKGROUND To investigate and compare the post-obturation pain after one-visit and two-visit root canal treatment in non-vital anterior teeth . MATERIAL S & METHODS One hundred forty eight patients requiring root canal therapy on permanent anterior non-vital teeth with single root were included in this study . Patients were r and omly assigned to either the one-appointment or the twoappointment group . The st and ardized protocol for all the teeth involved local anesthesia , isolation and access , engine-driven rotary nickel-titanium canal instrumentation with 2.5 % NaOCl irrigation and obturation . Teeth in group 1 ( n = 74 ) were obturated during the first appointment by using laterally condensed gutta-percha and resin sealer . Teeth in group 2 ( n = 74 ) were given closed dressing and were obturated during the second appointment , 7 to 14 days later . A modified Visual Analogue Scale was used to measure pain after 6 hours , 24 hours , 48 hours and 7 days after the treatment . Statistical analysis was done to compare groups at each interval by using an independent- sample s t test . RESULTS The incidence and intensity of post-obturation pain in both Group ' A ' and Group ' B ' gradually reduced over the study period . When the incidence of pain was compared in the single and two visit group , it was found that the single-visit group experienced slightly less pain than the two-visit group during all study intervals , but the difference found was not statistically significant . CONCLUSION There was no difference in postoperative pain between patients treated in only one appointment and patients treated in two appointments . The majority of patients in both groups reported no pain or only minimal pain after 7 days of treatment . How to cite the article : Rao KN , K and aswamy R , Umashetty G , Rathore VP , Hotkar C , Patil BS . Post-Obturation pain following one-visit and two-visit root canal treatment in necrotic anterior teeth . J Int Oral Health 2014;6(2):28 - 32 Aim The aim of this study was to evaluate the effect of simultaneous length control during root canal preparation on postoperative pain compared with separate working length determination and root canal preparation . The design was a parallel‐group , r and omized , controlled trial with 2 arms . Methods Forty‐four molar teeth were r and omly divided into 2 groups ( n = 22 ) , a control group ( separate length determination and root canal preparation ) and a simultaneous length control during root canal preparation group . The following variables were recorded : age ; gender ; tooth number ; preoperative pain on the visual analog scale ; pain level on days 1 , 3 , 5 , and 7 ; and analgesic intake after the procedure and initial/final percussion pain . The data were analyzed with the χ2 test , independent sample s t test , and Mann‐Whitney U test . Results The simultaneous length control during root canal preparation group result ed in lower postoperative pain levels on day 1 than did the control group ( P < .05 ) . Despite 2 patients ’ intake of postoperative analgesics in the control group , no patient needed to use postoperative analgesics in the simultaneous length control during root canal preparation group ( P > .05 ) . Conclusions Simultaneous length control during root canal preparation as a non‐pharmacologic strategy for reducing postoperative pain is a beneficial technique for preventing postoperative pain Phototherapy with low-level laser therapy ( LLLT ) and light-emitting diode therapy ( LEDT ) has arisen as an interesting alternative to drugs in treatments of musculoskeletal disorders . However , there is a lack of studies investigating the effects of combined use of different wavelengths from different light sources like lasers and light-emitting diodes ( LEDs ) in skeletal muscle disorders . With this perspective in mind , this study aim ed to investigate the effects of phototherapy with combination of different light sources on nonspecific knee pain . It was performed a r and omized , placebo-controlled , double-blinded clinical trial . Eighty-six patients rated 30 or greater on the pain visual analogue scale ( VAS ) were recruited and included in study . Patients of LLLT group received 12 treatments with active phototherapy ( with 905 nm super-pulsed laser and 875 and 640 nm LEDs , Manufactured by Multi Radiance Medical , Solon , OH , USA ) and conventional treatment ( physical therapy or chiropractic care ) , and patients of placebo group were treated at same way but with placebo phototherapy device . Pain assessment s ( VAS ) were performed at baseline , 4th , 7th , and 10th treatments , after the completion of treatments and at 1-month follow-up visit . Quality of life assessment s ( SF-36 ® ) were performed at baseline , after the completion of treatments and at 1-month follow-up visit . Our results demonstrate that phototherapy significantly decreased pain ( p < 0.05 ) from 10th treatment to follow-up assessment s and significantly improved ( p < 0.05 ) SF-36 ® physical component summary at posttreatments and follow-up assessment s compared to placebo . We conclude that combination of super-pulsed laser , red and infrared LEDs is effective to decrease pain and improve quality of life in patients with knee pain The purpose of this prospect i ve study was to assess the incidence of flare-ups ( a severe problem requiring an unscheduled visit and treatment ) among patients who received endodontic treatment by the two authors in their respective practice s during a period of one year , and also to examine the correlation with pre-operative and operative variables . The results showed an incidence of 1.58 % for flare-ups from 1012 endodontically treated teeth . Statistical analysis using the chi-square test ( P<0.05 ) indicated that flare-ups were found to be positively correlated with multiple appointments , retreatment cases , periradicular pain prior to treatment , presence of radiolucent lesions , and patients taking analgesic or anti-inflammatory drugs . In contrast , there was no correlation between flare-up , and age , sex , different arch/tooth groups and the status of the pulp Introduction : In this clinical trial , we evaluated the effect of low‐level laser therapy ( LLLT ) on postoperative pain in m and ibular molar teeth with symptomatic apical periodontitis . Methods : Forty‐two patients were included in the study according to the inclusion and exclusion criteria . Root canal treatment was conducted using reciprocating instruments . The patients were r and om Output:	Based on the current evidence , the use of LLLT for pain control in postendodontic therapy may be promising .
MS21359	*TASK* the task is to summarize an input biomedical literature in six sentences *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 several face-to-face programs are dedicated to informal caregivers of persons with dementia , they are not always accessible to overburdened or isolated caregivers . Based on a face-to-face intervention program , we adapted and design ed a Web-based fully automated psychoeducational program ( called Diapason ) inspired by a cognitive approach . Objective This study aim ed to evaluate through a pilot unblinded r and omized controlled trial the efficacy and acceptability of a Web-based psychoeducational program for informal caregivers of persons with Alzheimer ’s disease ( PWAD ) based on a mixed methods research design . Methods We recruited and r and omized offline 49 informal caregivers of a PWAD in a day care center in Paris , France . They either received the Web-based intervention and usual care for 3 months ( experimental group , n=25 ) or only usual care ( control group , n=24 ) . Caregivers ’ perceived stress ( PSS-14 , primary outcome ) , self-efficacy , burden , perceived health status , and depression ( secondary outcomes ) were measured during 3 face-to-face on-site visits : at baseline , at the end of the program ( month 3 ) , and after follow-up ( month 6 ) . Additionally , semistructured interviews were conducted with experimental group caregivers at month 6 and examined with thematic analysis . Results Intention-to-treat analysis did not show significant differences in self-perceived stress between the experimental and control groups ( P=.98 ) . The experimental group significantly improved their knowledge of the illness ( d=.79 , P=.008 ) from baseline to month 3 . Of the 25 participants allocated to the experimental group , 17 ( 71 % ) finished the protocol and entirely viewed at least 10 of 12 online sessions . On average , participants used the website 19.72 times ( SD 12.88 ) and were connected for 262.20 minutes ( SD 270.74 ) . The results of the satisfaction question naire showed that most participants considered the program to be useful ( 95 % , 19/20 ) , clear ( 100 % , 20/20 ) , and comprehensive ( 85 % , 17/20 ) . Significant correlations were found between relationship and caregivers ’ program opinion ( P=.01 ) . Thus , positive opinions were provided by husb and s and sons ( 3/3 ) , whereas qualified opinions were primarily reported by daughters ( 8/11 ) . Female spouses expressed negative ( 2/3 ) or neutral opinions ( 1/3 ) . Caregivers expected more dynamic content and further interaction with staff and peers . Conclusions In this study , quantitative results were inconclusive owing to small sample size . Qualitative results indicated/showed little acceptance of the program and high expectations from caregivers . Caregivers did not rule out their interest in this kind of intervention provided that it met their needs . More dynamic , personalized , and social interventions are desirable . Our recruitment issues pointed out the necessity of in-depth studies about caregivers ’ help-seeking behaviors and readiness factors . Trial Registration Clinical trials.gov NCT01430286 ; http:// clinical trials.gov/ct2/show/NCT01430286 ( Archived by WebCite at http://www.webcitation/6KxHaRspL ) OBJECTIVES To examine whether activity restriction specifically induced by fear of falling ( FF ) contributes to greater risk of disability and decline in physical function . DESIGN Prospect i ve cohort study . SETTING Population -based older cohort . PARTICIPANTS Six hundred seventy-three community-living elderly ( > or = 65 ) participants in the Invecchiare in Chianti Study who reported FF . MEASUREMENTS FF , fear-induced activity restriction , cognition , depressive symptoms , comorbidities , smoking history , and demographic factors were assessed at baseline . Disability in activities of daily living ( ADLs ) and instrumental activities of daily living ( IADLs ) and performance on the Short Performance Physical Battery ( SPPB ) were evaluated at baseline and at the 3-year follow-up . RESULTS One-quarter ( 25.5 % ) of participants did not report any activity restriction , 59.6 % reported moderate activity restriction ( restriction or avoidance of < 3 activities ) , and 14.9 % reported severe activity restriction ( restriction or avoidance of > or = 3 activities ) . The severe restriction group reported significantly higher IADL disability and worse SPPB scores than the no restriction and moderate restriction groups . Severe activity restriction was a significant independent predictor of worsening ADL disability and accelerated decline in lower extremity performance on SPPB over the 3-year follow-up . Severe and moderate activity restriction were independent predictors of worsening IADL disability . Results were consistent even after adjusting for multiple potential confounders . CONCLUSION In an elderly population , activity restriction associated with FF is an independent predictor of decline in physical function . Future intervention studies in geriatric preventive care should directly address risk factors associated with FF and activity restriction to substantiate long-term effects on physical abilities and autonomy of older persons 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 People with cognitive impairment and dementia have a poor outcome after a hip fracture surgery , about 30 - 50 % of all those who sustain a hip fracture have dementia . Therefore the aim was to investigate whether a multidisciplinary postoperative intervention program could reduce postoperative complications and improve functional recovery among people with dementia . METHODS A r and omized controlled trial with subgroup analyses among patients with dementia . Sixty-four patients with femoral neck fracture , aged ≥70 years at Umeå University Hospital , Sweden . The intervention consisted of staff education , individualized care planning and rehabilitation , active prevention , detection and treatment of postoperative complications , especially delirium . The staff worked in teams to apply comprehensive geriatric assessment , management and rehabilitation , including a follow-up at 4 months postoperatively . The control group followed conventional postoperative routines . RESULTS There were fewer postoperative complications in the intervention group such as urinary tract infections , p=0.001 ; nutritional problems , p=0.025 ; postoperative delirium , p=0.002 ; falls , p=0.006 . At 4 months a larger proportion in the intervention group had regained their previous independent indoor walking ability performance , p=0.005 . At 12 months a larger proportion in the intervention group had regained the activities of daily living ( ADL ) performance level they had before the fracture , p=0.027 . CONCLUSION This study demonstrates that patients with dementia who suffer a hip fracture can benefit from multidisciplinary geriatric assessment and rehabilitation and should not be excluded from rehabilitation programs INTRODUCTION Family carers play an important role in providing care for frail older Australians . Carers have increased rates of depression , burden and poor physical health compared with non-carers . Physical activity has been shown to improve outcomes ; however there is limited research investigating outcomes in older carers and less on physical activity for both the carer and care recipient . RESEARCH QUESTION Does a home-based individualised physical activity intervention design ed for both the carer and care recipient improve depression severity in older carers ? PARTICIPANTS AND SETTING 273 community-dwelling carers with depressive symptoms and their care recipients will be recruited for a r and omised controlled trial . Baseline assessment will consist of functional , psychological , and physical measures and information about service use . INTERVENTION AND CONTROL : Participants will be r and omised to receive either a physical activity program ( intervention ) , a social support program ( social control ) , or usual care ( control ) . The intervention and social control groups will have five home visits over six months . MEASUREMENTS All participants will be re-assessed after completion of the program and then six months later to evaluate sustainability of outcomes . The primary outcome measure is the 15-item Geriatric Depression Scale for carers . Secondary outcomes include physical measures for carers and care recipients , carer burden , carer satisfaction , care recipient depression , and cost-effectiveness . All assessors will be blind to group allocation . DISCUSSION This study has the potential to demonstrate that physical activity interventions can be delivered simultaneously to older carers and care recipients to improve mental and physical outcomes Abstract Objective : To evaluate the effect of intensive geriatric rehabilitation on demented patients with hip fracture . Design : Preplanned sub analysis of r and omised intervention study . Settting : Jyväskylä Central Hospital , Finl and . Participants : 243 independently living patients aged 65 years or older admitted to hospital with hip fracture . Intervention : After surgery patients in the intervention group ( n=120 ) were referred to the geriatric ward whereas those in the control group were discharged to local hospitals . Main outcome measures : Length of hospital stay , mortality , and place of residence three months and one year after surgery for hip fracture . Results : The median length of hospital stay of hip fracture patients with moderate dementia ( mini mental state examination score 12 - 17 ) was 47 days in the intervention group ( n=24 ) and 147 days in the control group ( n=12 , P=0.04 ) . The corresponding figures for patients with mild dementia ( score 18 - 23 ) were 29 days in the intervention group ( n=35 ) and 46.5 days in the control group ( n=42 , P=0.002 ) . Three months after the operation , in the intervention group 91 % ( 32 ) of the patients with mild dementia and 63 % ( 15 ) of the patients with moderate dementia were living independently . In the control group , the corresponding figures were 67 % ( 28 ) and 17 % ( 2 ) . There were no significant differences in mortality or in the lengths of hospital stay of severely demented patients and patients with normal mini mental state examination scores . Conclusions : Hip fracture patients with mild or moderate dementia can often return to the community if they are provided with active geriatric rehabilitation Background People with dementia progressively lose abilities and are prone to falling . Exercise- and activity-based interventions hold the prospect of increasing abilities , reducing falls , and slowing decline in cognition . Current falls prevention approaches are poorly suited to people with dementia , however , and are of uncertain effectiveness . We used multiple sources , and a co-production approach , to develop a new intervention , which we will evaluate in a feasibility r and omised controlled trial ( RCT ) , with embedded adherence , process and economic analyses . Methods We will recruit people with mild cognitive impairment or mild dementia from memory assessment clinics , and a family member or carer . We will r and omise participants between a therapy programme with high intensity supervision over 12 months , a therapy programme with moderate intensity supervision over 3 months , and brief falls assessment and advice as a control intervention . The therapy programmes will be delivered at home by mental health specialist therapists and therapy assistants . We will measure activities of daily living , falls and a battery of intermediate and distal health status outcomes , including activity , balance , cognition , mood and quality of life . The main aim is to test recruitment and retention , intervention delivery , data collection and other trial processes in advance of a planned definitive RCT . We will also study motivation and adherence , and conduct a process evaluation to help underst and why results occurred using mixed methods , including a qualitative interview study and scales measuring psychological , motivation and communication variables . We will undertake an economic study , including modelling of future impact and cost to end-of-life , and a social return on investment analysis . Discussion In this study , we aim Output:	The study suggested that the intervention is both feasible and acceptable to stakeholders . A number of modifications were recommended to address some of the issues arising during feasibility testing . The measurement of outcome measures was successful . The study has highlighted the feasibility of delivering a creative , tailored , individual approach to intervention for people with dementia following a fall . Although the intervention required greater investment of time than usual practice , many staff valued the opportunity to work more closely with people with dementia and their carers .
MS21360	*TASK* the task is to summarize an input biomedical literature in six sentences *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 predictive value of r and om urine sample during outpatient visit to predict persistent microalbuminuria was studied in 76 Type 1 , insulin-dependent diabetic subjects , 61 Type 2 , non-insulin-dependent diabetic subjects , and 72 Type 2 , insulin-treated diabetic subjects . Seventy-six patients attended outpatient clinic during morning , and 133 during afternoon . Microalbuminuria was suspected if Urinary Albumin Excretion ( UAE ) exceeded 20 mg/l . All patients were hospitalized within 6 months following outpatient visit , and persistent microalbuminuria was assessed then if UAE was between 30 and 300 mg/24 h on 2 - 3 occasions in 3 urines sample s. Of these 209 subjects eighty-three were also screened with Microbumintest ( Ames-Bayer ) , a semi-quantitative method . Among the 209 subjects , 71 were positive both for microalbuminuria during outpatient visit and a persistent microalbuminuria during hospitalization : sensitivity 91.0 % , specificity 83.2 % , concordance 86.1 % , and positive predictive value 76.3 % ( chi-squared test : 191 ; p less than 10(-4 ) ) . Data were not different for subjects examined on morning , or on afternoon . Among the 83 subjects also screened with Microbumintest , 22 displayed both a positive reaction and a persistent microalbuminuria : sensitivity 76 % , specificity 81 % , concordance 80 % , and positive predictive value 69 % ( chi-squared test : 126 ; p less than 10(-4 ) ) . Both types of screening appeared equally effective during outpatient visit . Hence , a persistent microalbuminuria can be predicted during an outpatient visit in a diabetic clinic BACKGROUND The first step in the diagnosis of diabetic nephropathy is to measure albumin in a spot urine sample . The aim of this study was to assess the accuracy of urinary albumin concentration ( UAC ) , urinary albumin-to-creatinine ratio ( UACR ) , and the Micral-Test II in a r and om urine specimen ( RUS ) for microalbuminuria screening in diabetes mellitus . METHODS Two hundred and seventy-eight patients collected 24 h timed urine specimens followed by RUS . Albumin ( immunoturbidimetry ) and creatinine were measured in protein-negative ( Combur-Test ) urine sample s. Sample s were classified as normoalbuminuric [ 24 h urinary albumin excretion rate ( UAER ) < 20 microg/min ; n = 189 ] and microalbuminuric ( UAER = 20 - 199 microg/min ; n = 89 ) . Micral-Test II readings were performed in 130 RUS . Receiver operating characteristics ( ROC ) curves were constructed using UAER as the reference st and ard . RESULTS The areas under the ROC curves were similar for UAC ( 0.934+/-0.032 ) and UACR ( 0.920+/-0.035 ; P = 0.626 ) , but the Micral-Test II had lower accuracy to diagnose microalbuminuria ( area = 0.846+/-0.047 ) than UAC ( P = 0.014 ) . The first cutoff point with 100 % sensitivity for UAC was 14.4 mg/l ( specificity = 77.2 % ) , and 15.7 mg/g for UACR ( specificity = 73.0 % ) . Concerning the Micral-Test II , sensitivity and specificity for the 20 mg/l cutoff point were 90.0 and 46.0 % , respectively . The agreement between UAER and the Micral-Test II for microalbuminuria diagnosis was 55.8 % ( kappa = 0.22 ; P < 0.001 ) . The cost of diagnosing microalbuminuria was 1.74 dollars(UAC ) , 2.00 dollars ( UACR ) and 4.09 dollars ( Micral-Test II ) per patient . CONCLUSIONS Measurement of UAC in a RUS was the best choice for the diagnosis screening of microalbuminuria in diabetic patients , considering cost and accuracy BACKGROUND Accurate measurement of proteinuria is important in the diagnosis and management of chronic kidney disease ( CKD ) . The reference st and ard test , 24-hour urinary protein excretion , is inconvenient and vulnerable to collection errors . Spot urine protein-creatinine ratio ( PCR ) is a convenient alternative and is in widespread use . However , day-to-day variability in PCR measurements has not been evaluated . STUDY DESIGN Prospect i ve cohort study of day-to-day variability in spot urine PCR measurement . SETTING & PARTICIPANTS Clinical ly stable out patients with CKD ( n = 145 ) attending a university hospital CKD clinic in Australia between July 2007 and April 2010 . INDEX TEST Spot urine PCR . OUTCOMES Spot PCR variability was assessed and repeatability limits were determined using fractional polynomials . MEASUREMENTS Spot PCRs were measured from urine sample s collected at 9:00 am on consecutive days and 24-hour urinary protein excretion was collected concurrently . RESULTS Paired results were analyzed from 145 patients : median age , 56 years ; 59 % men ; and median 24-hour urinary protein excretion , 0.7 ( range , 0.06 - 35.7 ) g/d . Day-to-day variability was substantial and increased in absolute terms , but decreased in relative terms with increasing baseline PCR . For patients with a low baseline PCR ( 20 mg/mmol [ 177 mg/g ] ) , a change greater than ±160 % ( repeatability limits , 0 - 52 mg/mmol [ 0 - 460 mg/g ] ) is required to indicate a real change in proteinuria status with 95 % certainty , whereas for those with a high baseline PCR ( 200 mg/mmol [ 1,768 mg/g ] ) , a change of ±50 % ( decrease to < 100 mg/mmol [ < 884 mg/g ] or increase to > 300 mg/mmol [ > 2,652 mg/g ] ) represents significant change . LIMITATIONS These study results need to be replicated in other ethnic groups . CONCLUSIONS Changes in PCR observed in patients with CKD , ranging from complete resolution to doubling of PCR values , could be due to inherent biological variation and may not indicate a change in disease status . This should be borne in mind when using PCR in the diagnosis and management of CKD The effectiveness of four urine screening tests-microalbumin ( MAlb ) , total protein ( TProt ) , total protein/creatinine ratio ( TProt/Cr R ) , and dipstick ( DPalb ) test for albumin-were evaluated for the detection of MAlb in r and om urine specimens . The following criteria were used to assess the effectiveness of each urine screening test : 100 % specificity ( no false positive results ) ; cost effectiveness ; rapidity and ease of performing the screening test ; and increased laboratory efficiency . A " gold st and ard " for presence of MAlb in r and om urine sample s was defined as a microalbumin/creatinine ratio ( MAlb/Cr R ) of > or = 30 mg/g . The least costly urine screening test was the DPalb , which , if assigned a value of 1.0 , allowed a cost ranking order for the screening tests-DPalb ( 1.0 ) < urine TProt ( 1.03 ) < urine TProt/Cr R ( 2.1 ) < urine MAlb ( 7.0 ) . Two hundred urine sample s from diabetic in patients and out patients were tested . Only two screening tests -- MAlb and DPalb -- achieved 100 % specificity without increasing laboratory costs ( small net savings ) , whereas the other two screening tests -- TProt and TProt/Cr R-only achieved 100 % specificity with increased laboratory costs . Theoretical prevalence rate analysis showed that urine MAlb screening would be effective at all prevalence rates for overt nephropathy . TProt and DPalb urine screening testing would be most effective in population s with prevalence rates of > or = 15 % for overt nephropathy . The TProt/Cr R ratio would only be effective in population s with prevalence rates of > or = 30 % . Of the four urine screening tests , only DPalb would significantly streamline the process of measuring urine MAlb . The dipstick test is inexpensive , easy and rapid to perform , does not delay measuring the ratio , since there is no wait for the screening test result , and can be used by referring laboratories to screen urine specimens before they are su bmi tted to a central laboratory , thereby reducing laboratory workload OBJECTIVE To evaluate single- sample urine collection s to determine their ability to screen patients for the presence of microalbuminuria . Microalbuminuria in patients with type I diabetes predicts the development of diabetic renal disease . RESEARCH DESIGN AND METHODS Cross-sectional analysis of single- sample urine collection techniques ( first morning void , r and om upright void ) and methods of albumin analysis ( RIA , reagent tablet ) were compared with conventional 24-h urine collection s ( RIA ) . The study included 94 patients ( 45 males , 49 females ; mean serum creatinine 88 μM ) with type I diabetes , selected from a screened population of 301 patients from the University Hospital Subspecialty Clinics . RESULTS A 24-hour urine collection RIA analysis for albumin revealed 36 normal patients ( < 30 mg ) , 27 with microalbuminuria ( 30–300 mg ) , and 31 with albuminuria ( > 300 mg ) . R and om upright urine sample s were more sensitive ( RIA 89 % , tablets 78 % ) for the detection of microalbuminuria than first morning void specimens ( RIA 70 % , tablets 60 % ) . Specificity was > 80 % with both r and om and first morning voids . CONCLUSIONS Screening for microalbuminuria can be performed in the clinic by r and om upright single- sample urine collection s. When reagent tablets were used , these results are available immediately . Patients who screen positive should be confirmed by 24-h or other timed urine collection OBJECTIVE To assess the performance of measurements of urinary albumin concentration ( UAC ) and urinary albumin : creatinine ratio ( UACR ) in a diurnal r and om urine specimen ( RUS ) for the screening of diabetic nephropathy . RESEARCH DESIGN AND METHODS A total of 95 ambulatory NIDDM patients ( 49 women , ages 40–75 years ) collected 123 RUSs during the morning after completing a timed 24-h urine collection . Albumin was measured by immunoturbidimetry . According to timed urinary albumin excretion rate ( UAER ) measured in the 24-h collection ( criterion st and ard ) , sample s were classified as normoalbuminuric ( UAER < 20 μg/min ; n = 54 ) , microalbuminuric ( UAER 20–200 μg/min ; n = 44 ) , and macroalbuminuric ( UAER > 200 μg/min ; n = 25 ) . The receiver operating characteristics ( ROC ) curve approach was used . The ROC curves of UAC and UACR in RUS for screening of microalbuminuria ( normo- and microalbuminuric sample s ; n = 98 ) and macroalbuminuria ( micro- and macroalbuminuric sample s ; n = 69 ) were plotted . RESULTS Spearman 's coefficients of correlation of 24-h UAER vs. UAC and UACR were 0.91 and 0.92 , respectively ( P < 0.001 ) . The calculated areas ( ± SE ) under the ROC curves to screen microalbuminuria for UAC ( 0.9766 ± 0.015 ) and UACR ( 0.9689 ± 0.014 ) were similar ( P > 0.05 ) as were the corresponding areas for macroalbuminuria ( 0.9868 ± 0.0094 and 0.9614 ± 0.0241 , respectively ; P > 0.05 ) . The first point with 100 % sensitivity and the point of intersection with a 100%-to-100 % diagonal for microalbuminuria were as follows : 16.9 and 33.6 mg/l for UAC and 15.0 and 26.8 mg/g for UACR ; for macroalbuminuria 174.0 and 296.2 mg/l for UAC and 116.0 and 334.3 mg/g for UACR , respectively . CONCLUSIONS Albumin measurements ( UAC and UACR ) in an RUS presented almost perfect accuracy for the screening of micro- and macroalbuminuria and UAC measured in an RUS is simpler and less expensive than UACR and UAER . It is suggested as a valid test for use in screening for diabetic nephropathy To assess the validity of urine albumin concentration ( UAC ) and the urine albumin : creatine ratio ( UACR ) in a r and om urine specimen ( Output:	The time point of urine collection did not affect the diagnostic performance of either test . AND RELEVANCE The UAC and the ACR yielded high sensitivity and specificity for the detection of microalbuminuria .
MS21361	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Continuous subcutaneous insulin infusion ( CSII ) is believed to decrease glycemic variability and clinical hypoglycemia compared with the multiple daily insulin ( MDI ) regimen . To compare the indices of glycemic instability between CSII and MDI , we analyzed the continuous glucose monitoring system ( CGMS ) ( Medtronic MiniMed , Northridge , CA ) profiles of a group of children with type 1 diabetes mellitus with history of frequent blood glucose ( BG ) fluctuations and hypoglycemia . PATIENTS AND METHODS Data from 14 ( nine girls , five boys ) patients ( 3.9 - 16.8 years old ) on CSII and 14 age- and sex-matched ( nine girls , five boys ) patients ( 3.9 - 16.0 years old ) on MDI with similar glycemic control ( hemoglobin A1c : 7.9 + /- 1.0 % vs. 7.9 + /- 1.5 % ) and body mass index ( BMI ) ( 20.1 + /- 4.3 vs. 19.9 + /- 4.1 kg/m(2 ) ) were evaluated by the CGMS . Mean BG ( MBG ) , absolute means of daily differences ( MODD ) , mean amplitude of glycemic excursion ( MAGE ) , and number of hypoglycemic events ( BG < 60 mg/dL ) for 48 h were calculated . RESULTS The MBG , MODD , MAGE , and number and mean duration of hypoglycemia events in the CSII group were similar to those in the MDI group . The MAGE had an inverse correlation with age ( CSII : r ( 2 ) = 0.52 , P = 0.003 ; MDI : r ( 2 ) = 0.29 , P < 0.04 ) and BMI ( CSII : r ( 2 ) = 0.38 , P < 0.02 ; MDI : r ( 2 ) = 0.71 , P < 0.0002 ) . However , there was a positive relationship between MAGE and bolus : basal insulin ratio in the CSII ( r ( 2 ) = 0.28 , P < 0.05 ) and MDI ( r ( 2 ) = 0.33 , P < 0.03 ) groups . Also , the MAGE had a positive correlation with frequency of hypoglycemic events in the CSII ( r ( 2 ) = 0.44 , P < 0.01 ) and MDI ( r ( 2 ) = 0.35 , P < 0.03 ) groups . CONCLUSIONS The CSII and MDI regimens in children and adolescents with comparable glycemic control displayed similar patterns of glycemic excursions , implying that factors influencing glycemic instability in pediatric type 1 diabetes mellitus appear to be independent of treatment modality OBJECTIVE To compare the efficacy of 2 intensified insulin regimens , continuous subcutaneous insulin infusion ( CSII ) and multiple daily injections ( MDI ) , by using the short-acting insulin analog lispro in type 1 diabetic patients . RESEARCH DESIGN AND METHODS A total of 41 C-peptide-negative type 1 diabetic patients ( age 43.5+/-10.3 years ; 21 men and 20 women , BMI 24.0+/-2.4 kg/m2 , diabetes duration 20.0+/-11.3 years ) on intensified insulin therapy ( MDI with regular insulin or lispro , n = 9 , CSII with regular insulin , n = 32 ) were included in an open-label r and omized crossover study comparing two 4-month periods of intensified insulin therapy with lispro : one period by MDI and the other by CSII . Blood glucose ( BG ) was monitored before and after each of the 3 meals each day . RESULTS The basal insulin regimen had to be optimized in 75 % of the patients during the MDI period ( mean number of NPH injections per day = 2.65 ) . HbA1c values were lower when lispro was used in CSII than in MDI ( 7.89+/-0.77 vs. 8.24+/-0.77 % , P<0.001 ) . BG levels were lower with CSII ( 165+/-27 vs. 175+/-33 mg/dl , P<0.05 ) . The SD of all the BG values ( 73+/-15 vs. 82+/-18 mg/dl , P<0.01 ) was lower with CSII . The frequency of hypoglycemic events , defined as BG levels < 60 mg/dl , did not differ significantly between the 2 modalities ( CSII 3.9+/-4.2 per 14 days vs. MDI 4.3+/-3.9 per 14 days ) . Mean insulin doses were significantly lower with CSII than with MDI ( 38.5+/-9.8 vs. 47.3+/-14.9 U/day . respectively , P < 0.0001 ) . CONCLUSIONS When used with external pumps versus MDI , lispro provides better glycemic control and stability with much lower doses of insulin and does not increase the frequency of hypoglycemic episodes OBJECTIVE This study assesses the effects of insulin pump therapy on diabetes control and family life in children 1 - 6 years old with type 1 diabetes . RESEARCH DESIGN AND METHODS Twenty-six children with type 1 diabetes for > /=6 months were r and omly assigned to current therapy ( two or three shots per day using NPH insulin and rapid-acting analog ) or continuous subcutaneous insulin infusion ( CSII ) for 6 months . After 6 months , current therapy subjects were offered CSII . Changes in HbA(1c ) , mean blood glucose ( MBG ) , hypoglycemia frequency , diabetes-related quality of life ( QOL ) , and parental adjustment were recorded . RESULTS Eleven subjects from each group completed the trial ( age 46.3 + /- 3.2 months [ means + /- SE ] ) . At baseline , there were no differences between groups in HbA(1c ) , MBG , age , sex , diabetes duration , or parental QOL . Mean HbA(1c ) , MBG , and parental QOL were similar between groups at 6 months . Mean HbA(1c ) and MBG did not change from baseline to 6 months in either group . The frequency of severe hypoglycemia , ketoacidosis , or hospitalization was similar between groups at any time period . Subjects on CSII had more fasting and predinner mild/moderate hypoglycemia at 1 and 6 months . Diabetes-related QOL improved in CSII fathers from baseline to 6 months . Psychological distress increased in current therapy mothers from baseline to 6 months . All subjects continued CSII after study completion . CONCLUSIONS CSII is safe and well tolerated in young children with diabetes and may have positive effects on QOL . CSII did not improve diabetes control when compared with injections , despite more mild/moderate hypoglycemia . The benefits and realistic expectations of CSII should be thoroughly examined before starting this therapy in very young children OBJECTIVE To compare glycemic patterns by mode of therapy in children with type 1 diabetes mellitus using the Continuous Glucose Monitoring System ( CGMS ) . DESIGN Open r and omized crossover comparing 3(1/2 ) months of multiple daily injections ( MDI ) and continuous subcutaneous insulin infusion ( CSII ) . SETTING Tertiary care , university-affiliated medical center . Patients Twenty-three children and adolescents with type 1 diabetes mellitus . INTERVENTIONS The CGMS was applied for 72 hours after 1 month and at the end of each study arm . MAIN OUTCOME MEASURES Hemoglobin A(1c ) levels and glucose level profiles were compared between the 2 study arms and the 2 sensor applications for each arm . RESULTS The arms were similar for mean ( SD ) hemoglobin A(1c ) levels ( CSII , 8.0 % [ 0.8 % ] ; and MDI , 8.2 % [ 0.8 % ] ) and glucose levels . Areas under the curve were significantly larger during MDI for nocturnal and 24-hour hypoglycemia ( P = .01 and .04 , respectively ) and for postpr and ial hypoglycemia and hyperglycemia ( P = .03 and .05 , respectively ) . The rate of hyperglycemia increased during CSII ( P = .03 ) , but 24-hour duration and area under the curve for hyperglycemia were similar . Compared with the first CGMS reading in each arm , the second had a longer mean duration of postpr and ial within-target glucose levels ( P = .04 ) , tendency for lower rate of diurnal hypoglycemic events ( P = .1 ) , shorter duration of nocturnal hypoglycemia ( P = .05 ) , and smaller 24-hour area under the curve for hypoglycemia ( P = .04 ) . CONCLUSIONS Intensive treatment with CSII seemed to be associated with slightly better prebreakfast , postpr and ial , and within-target glucose profiles than MDI , as well as a smaller area under the curve for hypoglycemia . Lower hypoglycemia-related variables in the second sensor reading in each arm indicate that the CGMS may serve as an educational tool to decrease the rate and magnitude of hypoglycemia OBJECTIVE The efficacy of the insulin analogs now available for multiple daily injection ( MDI ) and continuous subcutaneous insulin infusion ( CSII ) therapy in type 1 diabetes has not yet been established in pediatric patients . Our principal aim in this short-term study was to compare the efficacy of CSII to MDI with glargine in lowering HbA(1c ) levels in children and adolescents with type 1 diabetes . RESEARCH DESIGN AND METHODS Thirty-two youth with type 1 diabetes ( age 8 - 21 years ) were r and omly assigned to receive either MDI treatment with once-daily glargine and premeal/snack insulin aspart or CSII with insulin aspart . Dose titration in both groups was based on home self-monitored blood glucose measurements and monthly HbA(1c ) . HbA(1c ) , total daily insulin dose ( TDD ) , self-monitored blood glucose readings , and adverse events were compared after 16 weeks of therapy . RESULTS While there was no significant change in the glargine group ( HbA(1c ) 8.2 % at baseline vs. 8.1 % at 16 weeks ) , youth r and omized to CSII had a sharp reduction in HbA(1c ) levels , from 8.1 to 7.2 % after 16 weeks of therapy ( P < 0.02 vs. baseline and < 0.05 vs. glargine group ) . TDD was unchanged in the glargine group , but significantly dropped with CSII ( 1.4 units/kg at baseline vs. 0.9 units/kg at 16 weeks , P < 0.01 ) . Both groups had similar basal doses and insulin-to-carbohydrate ratios . Fasting self-monitored blood glucose was similar in both groups , but lunch , dinner , and bedtime readings were significantly lower in the CSII group ( P < 0.01 ) . CONCLUSIONS Lower HbA(1c ) and premeal glucose levels were more achievable in this short-term study with CSII than with glargine-based MDI treatment . CSII is an efficacious treatment to improve metabolic control in youth with type 1 diabetes OBJECTIVE To examine the efficacy and safety of using continuous subcutaneous insulin infusion ( CSII ) therapy in a large group of patients 18 months to 18 yr from a single pediatric diabetes program . RESEARCH DESIGN AND METHODS All patients < or = 18 yr of age starting on CSII from 1 January 1997 to 31 March 2000 at the Yale Children 's Diabetes Program were included . Clinical data were collected prospect ively before and during pump treatment . HbA1c was the primary efficacy outcome and rates of diabetes-related adverse events were the primary safety measures . RESULTS One hundred and sixty-one children ranging in age from 18 months to 18 yr received CSII for an average of 32 + /- 9 months when data collection was closed on 31 October 2001 , including 26 preschoolers ( < 7 yr ) , 76 school-agers ( 7 - 11 yr ) and 59 adolescents ( 12 - 18 yr ) . Mean HbA1c levels were 7.1 % in the preschoolers , 7.8 % in the school-agers and 8.1 % in the adolescents prior to the start of CSII . There was a significant and consistent reduction in mean HbA1c levels after 12 months of CSII ( to 6.5 % in preschoolers , 7.3 % in school-agers and 7.4 % in adolescents , p < 0.02 vs. prepump ) that was maintained at the most recent visit . Improved diabetes control was achieved with CSII without increasing daily insulin doses and in association with a decrease in the frequency of severe hypoglycemic events ( p < 0.05 vs. prepump , all three age groups combined ) . CONCLUSIONS CSII is an effective alternative to injection therapy in a large pediatric diabetes clinic setting . Even very young Output:	Combined data from all trials showed that the CSII group compared with the MDI group experienced a significant reduction in the level of glycosylated hemoglobin . In short-term insulin therapy , CSII compared with MDI is a more effective form of metabolic control and allows reducing the daily insulin requirement . Yet , no conclusions have been made so far whether this effect holds in later years .
MS21362	*TASK* the task is to summarize an input biomedical literature in six sentences *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 cardiovascular outcome data are available for blacks with hypertension treated with angiotensin-converting enzyme ( ACE ) inhibitors or calcium channel blockers ( CCBs ) . OBJECTIVE To determine whether an ACE inhibitor or CCB is superior to a thiazide-type diuretic in reducing cardiovascular disease ( CVD ) incidence in racial subgroups . DESIGN , SETTING , AND PARTICIPANTS Prespecified subgroup analysis of ALLHAT , a r and omized , double-blind , active-controlled , clinical outcome trial conducted between February 1994 and March 2002 in 33,357 hypertensive US and Canadian patients aged 55 years or older ( 35 % black ) with at least 1 other cardiovascular risk factor . INTERVENTIONS Antihypertensive regimens initiated with a CCB ( amlodipine ) or an ACE inhibitor ( lisinopril ) vs a thiazide-type diuretic ( chlorthalidone ) . Other medications were added to achieve goal blood pressures ( BPs ) less than 140/90 mm Hg . MAIN OUTCOME MEASURES The primary outcome was combined fatal coronary heart disease ( CHD ) or nonfatal myocardial infa rct ion ( MI ) , analyzed by intention-to-treat . Secondary outcomes included all-cause mortality , stroke , combined CVD ( CHD death , nonfatal MI , stroke , angina , coronary revascularization , heart failure [ HF ] , or peripheral vascular disease ) , and end-stage renal disease . RESULTS No significant difference was found between treatment groups for the primary CHD outcome in either racial subgroup . For amlodipine vs chlorthalidone only , HF was the only prespecified clinical outcome that differed significantly ( overall : relative risk [ RR ] , 1.37 ; 95 % confidence interval [ CI ] , 1.24 - 1.51 ; blacks : RR , 1.46 ; 95 % CI , 1.24 - 1.73 ; nonblacks : RR , 1.32 ; 95 % CI , 1.17 - 1.49 ; P<.001 for each comparison ) with no difference in treatment effects by race ( P = .38 for interaction ) . For lisinopril vs chlorthalidone , results differed by race for systolic BP ( greater decrease in blacks with chlorthalidone ) , stroke , and combined CVD outcomes ( P<.001 , P = .01 , and P = .04 , respectively , for interactions ) . In blacks and nonblacks , respectively , the RRs for stroke were 1.40 ( 95 % CI , 1.17 - 1.68 ) and 1.00 ( 95 % CI , 0.85 - 1.17 ) and for combined CVD were 1.19 ( 95 % CI , 1.09 - 1.30 ) and 1.06 ( 95 % CI , 1.00 - 1.13 ) . For HF , the RRs were 1.30 ( 95 % CI , 1.10 - 1.54 ) and 1.13 ( 95 % CI , 1.00 - 1.28 ) , with no significant interaction by race . Time-dependent BP adjustment did not significantly alter differences in outcome for lisinopril vs chlorthalidone in blacks . CONCLUSIONS In blacks and nonblack subgroups , rates were not lower in the amlodipine or lisinopril groups than in the chlorthalidone group for either the primary CHD or any other prespecified clinical outcome , and diuretic-based treatment result ed in the lowest risk of heart failure . While the improved outcomes with chlorthalidone were more pronounced for some outcomes in blacks than in nonblacks , thiazide-type diuretics remain the drugs of choice for initial therapy of hypertension in both black and nonblack hypertensive patients ABSTRACT Introduction : The use of herbal medicines including different types of tea is among the different strategies for preventing and controlling the side-effects of diabetes . The aim of the present study was to compare the effect of sour tea and green tea on mildly hypertensive patients with diabetes . Methods : The present study was a r and omized clinical trial in which 100 mildly hypertensive patients with diabetes were r and omly assigned into sour tea group ( ST ) and green tea group ( GT ) . They were instructed to drink sour tea and green tea infusion , respectively , three times a day 2 hr after each meal for 4 weeks . The participants ’ blood pressure was measured at days 1 , 15 , and at the end of study . Results : The systolic pressure of both groups statistically decreased at the end of the study ; it decreased from 123.1 ± 15.5 to 116.8 ± 16.3 mmHg in the ST and from 119.4 ± 15.1 to 114.8 ± 15.9 mmHg in the GT . The diastolic pressure of both groups statistically decreased by the end of the study ; it decreased from 79.4 ± 11.1 to 74.5 ± 9.3 mmHg in the ST and from 78.9 ± 8.3 to 75.3 ± 7.7 mmHg in the GT . The therapeutic effectiveness of tea drinking by the end of intervention was 43.5 % in the ST and 39.6 % in the GT compared to the beginning . Conclusions : The present study revealed that mildly hypertensive type 2 diabetic individuals who drink three glasses of green or sour tea daily for 4 weeks show significant decreased systolic and diastolic blood pressures Evidence suggests that berries contain bioactive compounds , which reduce certain cancers and hypertension . Our hypothesis was that daily blueberry ( BB ) consumption would increase natural killer ( NK ) cells and plasma redox capacity and reduce blood pressure , augmentation index ( AIx ) , central pulse wave velocity , and aortic systolic pressures ( ASPs ) . Twenty-five men and postmenopausal women aged 18 to 50 years were recruited and r and omized to BB ( n , 13 ) or placebo groups ( n , 12 ) . Participants were provided with BB ( equivalent to 250 g berries ) or placebo powders each day for 6 weeks . Blood pressure , vascular performance testing , and blood sample s were taken at baseline ( presupplementation ) . Participants returned after 6 weeks and repeated all procedures . Presupplementation to postsupplementation comparisons for the main effects of treatment , time , and treatment-time interaction were made using a 2 ( treatment ) × 2 ( times ) repeated- measures analysis of variance for all vascular measures , redox status , and NK cell counts . Anthropometric measures were compared using t tests . Body mass , composition , and overall blood pressures were not affected in either group . Overall , AIx and ASPs were decreased in BB ( treatment effect , P = .024 and P = .046 , respectively ) . Plasma redox was not affected . Absolute NK cells were increased in BB ( time , P = .001 and interaction , P = .012 ) . Subjects ( n , 9 ) with prehypertensive pressures ( ≥120/80 mm Hg , respectively ) were examined as a subset using t tests and exhibited significant reductions in diastolic pressure ( P = .038 ) from presupplementation to postsupplementation in BB . We conclude that BB ingestion for 6 weeks increases NK cells and reduces AIx , ASP , and diastolic pressures in sedentary males and females Dietary supplementation with whole blueberries in a pre clinical study result ed in a reduction in glucose concentrations over time . We sought to evaluate the effect of daily dietary supplementation with bioactives from blueberries on whole-body insulin sensitivity in men and women . A double-blinded , r and omized , and placebo-controlled clinical study design was used . After screening to resolve study eligibility , baseline ( wk 0 ) insulin sensitivity was measured on 32 obese , nondiabetic , and insulin-resistant subjects using a high-dose hyperinsulinemic-euglycemic clamp ( insulin infusion of 120 mU(861 pmol)⋅m(-2)⋅min(-1 ) ) . Serum inflammatory biomarkers and adiposity were measured at baseline . At the end of the study , insulin sensitivity , inflammatory biomarkers , and adiposity were reassessed . Participants were r and omized to consume either a smoothie containing 22.5 g blueberry bioactives ( blueberry group , n = 15 ) or a smoothie of equal nutritional value without added blueberry bioactives ( placebo group , n = 17 ) twice daily for 6 wk . Both groups were instructed to maintain their body weight by reducing ad libitum intake by an amount equal to the energy intake of the smoothies . Participants ' body weights were evaluated weekly and 3-d food records were collected at baseline , the middle , and end of the study . The mean change in insulin sensitivity improved more in the blueberry group ( 1.7 ± 0.5 mg⋅kg FFM(-1)⋅min(-1 ) ) than in the placebo group ( 0.4 ± 0.4 mg⋅kg FFM(-1)⋅min(-1 ) ) ( P = 0.04 ) . Insulin sensitivity was enhanced in the blueberry group at the end of the study without significant changes in adiposity , energy intake , and inflammatory biomarkers . In conclusion , daily dietary supplementation with bioactives from whole blueberries improved insulin sensitivity in obese , nondiabetic , and insulin-resistant participants BACKGROUND Dietary flavonoids have beneficial effects on blood pressure in intervention setting s , but there is limited information on habitual intake and risk of hypertension in population -based studies . OBJECTIVE We examined the association between habitual flavonoid intake and incident hypertension in a prospect i ve study in men and women . DESIGN A total of 87,242 women from the Nurses ' Health Study ( NHS ) II , 46,672 women from the NHS I , and 23,043 men from the Health Professionals Follow-Up Study ( HPFS ) participated in the study . Total flavonoid and subclass intakes were calculated from semiquantitative food-frequency question naires collected every 4 y by using an up date d and extended US Department of Agriculture data base . RESULTS During 14 y of follow-up , 29,018 cases of hypertension in women and 5629 cases of hypertension in men were reported . In pooled multivariate-adjusted analyses , participants in the highest quintile of anthocyanin intake ( predominantly from blueberries and strawberries ) had an 8 % reduction in risk of hypertension [ relative risk ( RR ) : 0.92 ; 95 % CI : 0.86 , 0.98 ; P < 0.03 ] compared with that for participants in the lowest quintile of anthocyanin intake ; the risk reduction was 12 % ( RR : 0.88 ; 95 % CI : 0.84 , 0.93 ; P < 0.001 ) in participants ≤60 y of age and 0.96 ( 0.91 , 1.02 ) in participants > 60 y of age ( P for age interaction = 0.02 ) . Although intakes of other subclasses were not associated with hypertension , pooled analyses for individual compounds suggested a 5 % ( 95 % CI : 0.91 , 0.99 ; P = 0.005 ) reduction in risk for the highest compared with the lowest quintiles of intake of the flavone apigenin . In participants ≤60 y of age , a 6 % ( 95 % CI : 0.88 , 0.97 ; P = 0.002 ) reduction in risk was observed for the flavan-3-ol catechin when the highest and the lowest quintiles were compared . CONCLUSIONS Anthocyanins and some flavone and flavan-3-ol compounds may contribute to the prevention of hypertension . These vasodilatory properties may result from specific structural similarities ( including the B-ring hydroxylation and methyoxylation pattern ) OBJECTIVE Evaluation of the vitro antioxidant activity of green and black tea , their in vivo effect on plasma antioxidant potential in man and the effect of milk addition . DESIGN The antioxidant activity of the tea , with and without milk , was tested in vitro by measuring the length of the peroxyl radical induced lag-phase . The in vivo activity was tested on two groups of five healthy adults . Each group ingested 300 ml of either black or green tea , after overnight fast . The experiment was repeated on a separate day , adding 100 ml whole milk to the tea ( ratio 1:4 ) . Five subjects acted as controls . The human plasma antioxidant capacity ( TRAP ) was measured before and 30 , 50 and 80 min from the ingestion of tea . RESULTS Both teas inhibited the in vitro peroxidation in a dose-dependent manner . Green tea was sixfold more potent than black tea . The addition of milk to either tea did not appreciably modify their in vitro antioxidant potential . In vivo , the ingestion of tea produced a significant increase of TRAP ( P < 0.05 ) , similar in both teas , which peaked at 30 - 50 min . When tea was consumed with milk , their in vivo activity was totally inhibited . CONCLUSIONS The paper shows that tea possesses a Output:	In summary , the results from this meta- analysis do not favor any clinical efficacy of blueberry supplementation in improving BP .
MS21363	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Muscle mass decreases with age , leading to " sarcopenia , " or low relative muscle mass , in elderly people . Sarcopenia is believed to be associated with metabolic , physiologic , and functional impairments and disability . Methods of estimating the prevalence of sarcopenia and its associated risks in elderly population s are lacking . Data from a population -based survey of 883 elderly Hispanic and non-Hispanic white men and women living in New Mexico ( the New Mexico Elder Health Survey , 1993 - 1995 ) were analyzed to develop a method for estimating the prevalence of sarcopenia . An anthropometric equation for predicting appendicular skeletal muscle mass was developed from a r and om sub sample ( n = 199 ) of participants and was extended to the total sample . Sarcopenia was defined as appendicular skeletal muscle mass (kg)/height2 ( m2 ) being less than two st and ard deviations below the mean of a young reference group . Prevalences increased from 13 - 24 % in persons under 70 years of age to > 50 % in persons over 80 years of age , and were slightly greater in Hispanics than in non-Hispanic whites . Sarcopenia was significantly associated with self-reported physical disability in both men and women , independent of ethnicity , age , morbidity , obesity , income , and health behaviors . This study provides some of the first estimates of the extent of the public health problem posed by sarcopenia Exercise training improves vascular function in subjects with cardiovascular disease and risk factors , but there is mounting evidence these vascular adaptations may be vessel bed specific . We have therefore examined the hypothesis that exercise-induced improvements in conduit vessel function are related to changes in resistance vessel function . Endothelium-dependent and -independent conduit vessel function were assessed by using wall-tracking of high-resolution brachial artery ultrasound images of the response to flow-mediated dilation ( FMD ) and nitroglycerine [ glyceryl trinitrate ( GTN ) ] administration . Resistance vessel endothelium-dependent and -independent function were assessed using intrabrachial administration of acetylcholine ( ACh ) and nitroprusside ( SNP ) . R and omized crossover studies of 8-wk exercise training were undertaken in untreated hypercholesterolemic ( n = 10 ) , treated hypercholesterolemic ( n = 10 ) , coronary artery disease ( n = 8) , and Type 2 diabetic subjects ( n = 15 ) . Exercise training significantly enhanced responses to ACh ( P < 0.05 ) and FMD ( P < 0.0001 ) . There were no significant changes in either SNP or GTN responses . The correlation between ACh and FMD responses at entry was not significant ( r = 0.186 ; P = 0.231 ) , and training-induced changes in the ACh did not correlate with those in FMD ( r = -0.022 ; P = 0.890 ) . Similarly , no correlation was evident between the SNP and GTN responses at entry ( r = -0.010 ; P = 0.951 ) or between changes in these variables with training ( r = -0.211 ; P = 0.191 ) . We conclude that , although short-term exercise training improves endothelium-dependent nitric oxide-mediated vascular function in both conduit and resistance vessels , the magnitude of these improvements are unrelated BACKGROUND Exercise training improves physical fitness , insulin resistance , and endothelial function in type 2 diabetes . Hypoxia may further optimize these beneficial effects . The aim of this study was to compare the effects of hypoxic versus normoxic exercise training on physical fitness , endothelial function , and insulin resistance in type 2 diabetes . METHODS Peak oxygen consumption , flow mediated dilation ( endothelial function ) , and glucose homeostasis were assessed in 19 patients ( 55±7 years ) before and after an 8-week intervention . Subjects were r and omly allocated to normoxic ( 21 % O2 , n=9 ) or hypoxic ( 16.5 % O2 , n=10 ) exercise training . Endothelium-independent dilation was examined using sublingual administration of glyceryl trinitrate , and used to calculate the ratio between endothelium-dependent and -independent dilation . RESULTS Exercise training improved physical fitness and brachial artery ratio between endothelium-dependent and -independent dilation ( both p<0.05 ) , whilst these exercise training-induced changes were similar in both groups ( interaction-effects p>0.05 ) . Exercise training did not significantly change brachial artery flow-mediated dilation or glyceryl trinitrate-response , superficial femoral artery flow-mediated dilation , or glucose homeostasis , whilst hypoxia did not alter the impact of exercise training . CONCLUSION Contrary to our hypothesis , hypoxia does not potentiate the effect of exercise training on physical fitness , vascular function , or glucose homeostasis in type 2 diabetes OBJECTIVE To investigate the effect of an exercise intervention on flow-mediated dilation ( FMD ) and circulating endothelial biomarkers in adults with type 2 diabetes ( T2DM ) . METHODS Sedentary adults ( n = 140 ) , aged 40 - 65 , with T2DM and untreated pre or Stage I hypertension or treated hypertension were r and omized to a 6-month , supervised , exercise program ( 3 × week ) or a sedentary control . Assessment s included BMI , body and visceral fat , blood pressure , lipids , HbA1c , insulin sensitivity ( QUICKI ) , fitness , FMD , E-selectin , P-selectin , intracellular and vascular cellular adhesion molecules ( ICAM , VCAM ) , and tissue plasminogen activator ( tPA ) . Intervention effects were compared by t-tests . Pearson 's correlations were calculated between changes in cardiovascular risk factors and endothelial outcomes . RESULTS Exercisers significantly improved BMI ( -0.6 kg/m(2 ) ) , body fat % ( -1.4 % ) , HbA1c ( -0.5 % ) , and fitness ( 2.9 mL/kg min ) vs. controls ( p < 0.05 ) . However , there were no differences between groups in changes in FMD , E-selectin , P-selectin , ICAM , VCAM , or tPA . Among exercisers , changes in cardiovascular risk factors correlated with several biomarkers . Decreased P-selectin correlated with decreased BMI ( r = 0.29 , p = 0.04 ) and increased HDL cholesterol ( r = -0.36 , p = 0.01 ) . Decreased ICAM correlated with decreased triglycerides and HbA1c ( r = 0.30 , p = 0.04 ; r = 0.31 , p = 0.03 ) and increased QUICKI ( r = - 0.28 , p = 0.05 ) . Decreased tPA correlated with decreased total body and visceral fat ( r = 0.28 , p = 0.05 ; r = 0.38 , p = 0.008 ) and increased QUICKI ( r = -0.38 , p = 0.007 ) . CONCLUSIONS While exercise result ed in improved fitness , body composition , and glycemic control , there were no changes in FMD or circulating endothelial biomarkers . The associations of changes in cardiovascular risk factors and endothelial biomarkers suggest that improvement in risk factors could mediate the exercise-induced improvements in endothelial function seen in prior studies BACKGROUND AND AIMS Very-low carbohydrate diets can improve glycaemic control in patients with type 2 diabetes ( T2DM ) . However , compared to traditional higher carbohydrate , low fat ( HighCHO ) diets , they have been associated with impaired endothelial function ( measured by flow mediated dilatation [ FMD ] ) that is possibly related to saturated fat . This study aim ed to examine the effects of a 12-month hypocaloric very-low carbohydrate , low saturated fat ( LowCHO ) diet compared to an isocaloric HighCHO diet . METHODS One hundred and fifteen obese patients with T2DM ( age:58.4 ± 0.7 [ SEM ] yr , BMI : 34.6 ± 0.4 kg/m(2 ) , HbA1c:7.33 [ 56.3 mmol/mol ] ± 0.10 % ) were r and omised to consume an energy restricted LowCHO diet ( Carb : Pro : Fat : Sat-Fat 14:28:58 : < 10 % energy ; n = 58 ) or isocaloric HighCHO diet ( 53:17:30 : < 10 % ; n = 57 ) whilst undertaking exercise ( 60 min , 3/wk ) . Bodyweight , HbA1c and FMD were assessed . RESULTS Seventy eight participants completed the intervention ( LowCHO = 41 , HighCHO = 37 ) . Both groups experienced similar reductions in weight and HbA1c ( -10.6 ± 0.7 kg , -1.05 ± 0.10 % ; p < 0.001 time , p ≥ 0.48 time × diet ) . FMD did not change ( p = 0.11 time , p = 0.20 time × diet ) . CONCLUSIONS In patients with obesity and T2DM , HighCHO diet and LowCHO diet have similar effects on endothelial function To determine the effects of continuous aerobic exercise training ( CON ) vs interval aerobic exercise training ( INT ) on glycemic control and endothelium-dependent vasodilatation , 43 participants with type 2 diabetes were r and omly allocated to the sedentary , CON , and INT groups . The CON and INT exercise training programs were design ed to yield the same energy expenditure/exercise session and included walking on treadmill for 30 and 40 min/day , 3 times/week for 12 weeks . Body fatness and heart rate at rest decreased and leg muscle strength increased ( all P < 0.05 ) in both the CON and INT groups . Fasting blood glucose levels decreased ( P < 0.05 ) in both exercise groups but glycosylated hemoglobin levels decreased ( P < 0.05 ) only in the INT group . Maximal aerobic capacity , flow-mediated dilation , and cutaneous reactive hyperemia increased significantly in both exercise groups ; however , the magnitude of improvements was greater in the INT group . Only the INT group experienced reductions in erythrocyte malondialdehyde and serum von Willebr and factor and increases in plasma glutathione peroxidase and nitric oxide ( all P < 0.05 ) . We concluded that both continuous and interval training were effective in improving glycemic control , aerobic fitness , and endothelium-dependent vasodilation , but the interval training program appears to confer greater improvements than the continuous training program AIMS To determine if type 2 diabetes mellitus ( T2D ) differentiates endothelial function and plasma nitrite response ( a marker of nitric oxide bioavailability ) during exercise in peripheral arterial disease ( PAD ) subjects prior to and following 3 months supervised exercise training ( SET ) . METHODS In subjects with T2D+PAD ( n = 13 ) and PAD-only ( n = 14 ) , endothelial function was measured using brachial artery flow-mediated dilation . On a separate day , venous blood draws were performed at rest and 10 min following a symptom-limited grade d treadmill test ( SL-GXT ) . Plasma sample s were snap-frozen for analysis of nitrite by reductive chemiluminescence . All testing was repeated following 3 months of SET . RESULTS Prior to training both groups demonstrated endothelial dysfunction , which was correlated with a net decrease in plasma nitrite following a SL-GXT ( p ≤ 0.05 ) . Following SET , the PAD-only group demonstrated an improvement in endothelial function ( p ≤ 0.05 ) and COT ( p ≤ 0.05 ) , which was related to a net increase in plasma nitrite following the SL-GXT ( both p ≤ 0.05 ) . The T2D+PAD group had none of these increases . CONCLUSIONS T2D in the presence of PAD attenuated improvements in endothelial function , net plasma nitrite , and COT following SET . This suggests that T2D maybe associated with an inability to endogenously increase vascular NO bioavailability to SET Background : Resistance training has been increasingly incorporated into the overall exercise programme because of its effect on muscle strength , functional capacity and osteoporosis . High-intensity resistance training increases arterial stiffness . However , the effect of moderate-intensity resistance training on arterial stiffness is unknown . Objective : To determine whether 12 weeks of moderate-intensity resistance training increases arterial stiffness in middle-aged women . Methods : 35 middle-aged women ( age range 32 to 59 years ) volunteered to participate . The subjects were r and omly assigned to one of three groups : resistance training ( RT ) group , aerobic exercise training ( AET ) group or control group . The RT and AET groups performed 12 weeks of moderate-intensity resistance training or aerobic exercise training ( two days/week ) . Results : In the RT group , one-repetition maximum strength significantly increased after the intervention . Interestingly , aortic ( carotid Output:	Conclusion Our results suggest that in patients with T2D , lower intensity exercise has physiological meaningful effects on EF , in support of the emerging concept that the lower efforts of exercise are not necessarily less cardioprotective than higher intensity training
MS21364	*TASK* the task is to summarize an input biomedical literature in six sentences *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 studied the effect on tumour response to neoadjuvant therapy of the substitution of lapatinib for trastuzumab in combination with weekly paclitaxel after doxorubicin plus cyclophosphamide treatment , and of the addition of lapatinib and trastuzumab combined after doxorubicin plus cyclophosphamide treatment in patients with HER2-positive operable breast cancer to determine whether there would be a benefit of dual HER2 blockade in these patients . METHODS For this open-label , r and omised phase 3 trial we recruited women aged 18 years or older with an ECOG performance status of 0 or 1 with operable HER2-positive breast cancer . Each received four cycles of st and ard doxorubicin 60 mg/m(2 ) and cyclophosphamide 600 mg/m(2 ) intravenously on day 1 every 3 weeks followed by four cycles of weekly paclitaxel ( 80 mg/m(2 ) ) intravenously on days 1 , 8 , and 15 , every 4 weeks . Concurrently with weekly paclitaxel , patients received either trastuzumab ( 4 mg/kg load , then 2 mg/kg intravenously ) weekly until surgery , lapatinib ( 1250 mg orally ) daily until surgery , or weekly trastuzumab plus lapatinib ( 750 mg orally ) daily until surgery . After surgery , all patients received trastuzumab to complete 52 weeks of HER2-targeted therapy . R and omisation ( ratio 1:1:1 ) was done central ly with stratification by clinical tumour size , clinical nodal status , hormone-receptor status , and age . The primary endpoint was the pathological complete response in the breast , and analysis was performed on an intention-to-treat population . FINDINGS Patient accrual started on July 16 , 2007 , and was completed on June 30 , 2011 ; 529 women were enrolled in the trial . 519 patients had their pathological response determined . Breast pathological complete response was noted in 93 ( 52·5 % , 95 % CI 44·9 - 59·5 ) of 177 patients in the trastuzumab group , 91 ( 53·2 % , 45·4 - 60·3 ) of 171 patients in the lapatinib group ( p=0·9852 ) ; and 106 ( 62·0 % , 54·3 - 68·8 ) of 171 patients in the combination group ( p=0·095 ) . The most common grade 3 and 4 toxic effects were neutropenia ( 29 [ 16 % ] patients in the trastuzumab group [ grade 4 in five patients ( 3 % ) , 28 [ 16 % ] in the lapatinib group [ grade 4 in eight patients ( 5 % ) ] , and 29 [ 17 % ] in the combination group [ grade 4 in nine patients ( 5 % ) ] ) and grade 3 diarrhoea ( four [ 2 % ] patients in the trastuzumab group , 35 [ 20 % ] in the lapatinib group , and 46 [ 27 % ] in the combination group ; p<0·0001 ) . Symptomatic congestive heart failure defined as New York Heart Association Class III or IV events occurred in seven ( 4 % ) patients in the trastuzumab group , seven ( 4 % ) in the lapatinib group , and one ( < 1 % ) in the combination group ; p=0·185 ) . INTERPRETATION Substitution of lapatinib for trastuzumab in combination with chemotherapy result ed in similar high percentages of pathological complete response . Combined HER2-targeted therapy produced a numerically but insignificantly higher pathological complete response percentage than single-agent HER2-directed therapy ; these findings are consistent with results from other studies . Trials are being undertaken to further assess these findings in the adjuvant setting BACKGROUND In metastatic breast cancer , nab-paclitaxel has been shown to significantly increase progression-free survival compared with solvent-based paclitaxel . The GeparSepto ( GBG 69 ) trial assessed whether weekly nab-paclitaxel could increase the proportion of patients achieving pathological complete response compared with weekly solvent-based paclitaxel , both followed by epirubicin plus cyclophosphamide as neoadjuvant treatment . METHOD In a phase 3 r and omised trial , we enrolled patients with previously untreated unilateral or bilateral primary invasive breast cancer and r and omly assigned them in a 1:1 ratio using dynamic allocation and Pocock minimisation by breast cancer subtype , Ki67 and SPARC expression . Patients were treated for 12 weeks with either intravenous nab-paclitaxel 150 mg/m(2 ) ( after study amendment , 125 mg/m(2 ) ) on days 1 , 8 , and 15 for four 3-week cycles , or solvent-based intravenous paclitaxel 80 mg/m(2 ) on days 1 , 8 , and 15 for four 3-week cycles . Taxane treatment was followed in both groups by intravenous epirubicin 90 mg/m(2 ) plus intravenous cyclophosphamide 600 mg/m(2 ) on day 1 for four 3-week cycles . Patients with HER2-positive tumours received concurrent trastuzumab 6 mg/kg ( loading dose 8 mg/kg ) and pertuzumab 420 mg ( loading dose 840 mg ) on day 1 of every 3-week cycle . Trastuzumab and pertuzumab were given every 3 weeks concomitantly with chemotherapy for all cycles . This report is the final analysis of the primary endpoint , pathological complete response ( ypT0 ypN0 ) , analysed for all patients who started treatment ( modified intention to treat ) . We used a closed test procedure to test for non-inferiority , with the nab-paclitaxel group calculated as non-inferior to the solvent-based paclitaxel group if the lower 95 % CI for the OR was above 0·858 ( OR equivalent to pathological complete response [ 33 % ] minus a 10 % non-inferiority margin [ 3·3 % ] ; 29·7 % ) . We planned to test for superiority only in case of a positive non-inferiority test , using an α of 0·05 . Safety was assessed in all patients who received study drug . The trial is registered with Clinical Trials.gov , number NCT01583426 . FINDINGS Between July 30 , 2012 , and Dec 23 , 2013 , we r and omly assigned 1229 women , of whom 1206 started treatment ( 606 with nab-paclitaxel and 600 with solvent-based paclitaxel ) . The nab-paclitaxel dose was reduced after enrolment of 464 participants to 125 mg/m(2 ) due to increased treatment discontinuation and sensory neuropathy in this group . Pathological complete response occurred more frequently in the nab-paclitaxel group ( 233 [ 38 % , 95 % CI 35 - 42 ] patients ) than in the solvent-based paclitaxel group ( 174 [ 29 % , 25 - 33 ] patients ; OR 1·53 , 95 % CI 1·20 - 1·95 ; unadjusted p=0·00065 ) . The incidence of grade 3 - 4 anaemia ( 13 [ 2 % ] of 605 patients in the nab-paclitaxel group vs four [ 1 % ] of patients in the solvent-based paclitaxel group ; p=0·048 ) and peripheral sensory neuropathy grade 3 - 4 ( 63 [ 10 % ] patients receiving any nab-paclitaxel dose ; 31 [ 8 % ] of patients starting with 125 mg/m(2 ) and 32 [ 15 % ] of patients starting with 150 mg/m(2 ) ; vs 16 [ 3 % ] in the solvent-based paclitaxel group , p<0·001 ) was significantly higher for nab-paclitaxel than for solvent-based paclitaxel . Overall , 283 ( 23 % ) patients were noted to have at least one serious adverse event ( based on study drug received ) , 156 ( 26 % ) in the nab-paclitaxel group and 127 ( 21 % ) in the solvent-based paclitaxel group ( p=0·057 ) . There were three deaths ( during epirubicin plus cyclophosphamide treatment ) in the nab-paclitaxel group ( due to sepsis , diarrhoea , and accident unrelated to the trial ) versus one in the solvent-based paclitaxel group ( during paclitaxel treatment ; cardiac failure ) . INTERPRETATION Substituting solvent-based paclitaxel with nab-paclitaxel significantly increases the proportion of patients achieving a pathological complete response rate after anthracycline-based chemotherapy . These results might lead to an exchange of the preferred taxane , solvent-based paclitaxel , for nab-paclitaxel in therapy for primary breast cancer . FUNDING Celgene , Roche BACKGROUND Pertuzumab ( P ) combined with trastuzumab (H)-based chemotherapy improves efficacy in early and advanced HER2-positive breast cancer . We assessed the tolerability , with particular focus on cardiac safety , of H and P with chemotherapy in the neoadjuvant treatment of HER2-positive early breast cancer . PATIENTS AND METHODS In this multicenter , open-label phase II study , patients with operable , locally advanced , or inflammatory breast cancer were r and omized 1 : 1 : 1 to receive six neoadjuvant cycles q3w ( Arm A : 5-fluorouracil , epirubicin , cyclophosphamide [ FEC ] + H + P ×3 → docetaxel [ T ] + H + P ×3 ; Arm B : FEC ×3 → T + H + P ×3 ; Arm C : T + carboplatin + H [TCH]+P ×6 ) . pCR was assessed at surgery and adjuvant therapy given to complete 1 year of H. RESULTS Two hundred twenty-five patients were r and omized . During neoadjuvant treatment , two patients ( 2.7 % ; Arm B ) experienced symptomatic left ventricular systolic dysfunction ( LVSD ) and 11 patients ( Arm A : 4 [ 5.6 % ] ; Arm B : 4 [ 5.3 % ] ; Arm C : 3 [ 3.9 % ] ) had declines in left ventricular ejection fraction of ≥10 % points from baseline to < 50 % . Diarrhea was the most common adverse event . pCR ( ypT0/is ) was reported for 61.6 % ( Arm A ) , 57.3 % ( Arm B ) , and 66.2 % ( Arm C ) of patients . CONCLUSION The combination of P with H and st and ard chemotherapy result ed in low rates of symptomatic LVSD BACKGROUND If treatment of the axilla is indicated in patients with breast cancer who have a positive sentinel node , axillary lymph node dissection is the present st and ard . Although axillary lymph node dissection provides excellent regional control , it is associated with harmful side-effects . We aim ed to assess whether axillary radiotherapy provides comparable regional control with fewer side-effects . METHODS Patients with T1 - 2 primary breast cancer and no palpable lymphadenopathy were enrolled in the r and omised , multicentre , open-label , phase 3 non-inferiority EORTC 10981 - 22023 AMAROS trial . Patients were r and omly assigned ( 1:1 ) by a computer-generated allocation schedule to receive either axillary lymph node dissection or axillary radiotherapy in case of a positive sentinel node , stratified by institution . The primary endpoint was non-inferiority of 5-year axillary recurrence , considered to be not more than 4 % for the axillary radiotherapy group compared with an expected 2 % in the axillary lymph node dissection group . Analyses were by intention to treat and per protocol . The AMAROS trial is registered with Clinical Trials.gov , number NCT00014612 . FINDINGS Between Feb 19 , 2001 , and April 29 , 2010 , 4823 patients were enrolled at 34 centres from nine European countries , of whom 4806 were eligible for r and omisation . 2402 patients were r and omly assigned to receive axillary lymph node dissection and 2404 to receive axillary radiotherapy . Of the 1425 patients with a positive sentinel node , 744 had been r and omly assigned to axillary lymph node dissection and 681 to axillary radiotherapy ; these patients constituted the intention-to-treat population . Median follow-up was 6·1 years ( IQR 4·1 - 8·0 ) for the patients with positive sentinel lymph nodes . In the axillary lymph node dissection group , 220 ( 33 % ) of 672 patients who underwent axillary lymph node dissection had additional positive nodes . Axillary recurrence occurred in four of 744 patients in the axillary Output:	Breast surgery performed after NAT does not reflect tumour response , result ing in potentially unnecessary radical surgery , especially mastectomy .
MS21365	*TASK* the task is to summarize an input biomedical literature in six sentences *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 developed a Dutch outpatient multidisciplinary group treatment ( Go4it ) for obese adolescents , including cognitive behavioural therapy and education on healthy dietary and physical activity behaviour . This study examined the effect of Go4it on Health Related Quality of Life ( HRQoL ) . Methods At our outpatient paediatric obesity clinic , obese adolescents ( n = 122 , 11–18 years ) were r and omly assigned to 1 ) Go4it , 7 sessions with an interval of 2 weeks or 2 ) current regular care consisting of referral to a dietician in the home care setting ( controls ) . Linear mixed model analysis was performed to evaluate the intervention effects on HRQoL at 6 and 18-month follow-ups . HRQoL indicators included the Child Health Question naire , the Paediatric Quality of Life Inventory ™ Version 4.0 ( PedsQL ™ 4.0 ) , and the Body Esteem Scale ( BES ) . Results In total , 95 adolescents ( Go4it 57 , controls 38 ) were included in the current analysis with a mean age of 14.5 ± 1.7 and mean BMI -SDS of 2.9 ± 0.5 . At baseline , all participants experienced lower levels of physical and psychosocial well-being compared to a normal weight reference group . At the 18 month follow-up , we found small but beneficial intervention effects on all subscales of the PedsQL ™ 4.0 and BES question naires . Two subscales improved significantly ; i.e. , physical health ( between group difference 5.4 ; 95%CI : 0.3 ; 10.6 ) , and school functioning ( between group difference 7.4 ; 95%CI : 1.6 ; 13.2 ) . Conclusion Obese adolescents experienced lower HRQoL than their healthy peers . The Go4it intervention had small beneficial effects on HRQoL compared to the current regular care practice s for obese adolescents . Trial registration Netherl and s Trial Register : IS RCT N27626398 , METC number : 05.134 ( WMO , monocenter ) Background There is an urgent need for innovative and developmentally appropriate lifestyle interventions to promote healthy lifestyle behaviors and to prevent the early onset of type 2 diabetes and cardiovascular disease risk in obese Latino adolescents . Guided imagery offers promise to reduce stress and promote lifestyle behavior change to reduce disease risk in obese adolescents . Our objectives were : 1 ) To pilot test a new 12-wk lifestyle intervention using a r and omized trial design in obese Latino adolescents , in order to determine the effects of the mind-body modality of Interactive Guided ImagerySM ( IGI ) , over and above those of a didactic lifestyle education , on insulin resistance , eating and physical activity behaviors , stress and stress biomarkers ; and 2 ) To explore the role of intervention-related changes in stress and stress biomarkers on changes in metabolic outcomes , particularly insulin resistance . Methods Obese ( BMI > 95th percentile ) , Latino adolescents ( n = 35 , age 14 - 17 ) were r and omized to receive either 12 weekly sessions of a lifestyle education plus guided imagery program ( GI ) , or lifestyle education plus a digital storytelling computer program ( DS ) . Between-group differences in behavioral , biological , and psychological outcomes were assessed using unpaired T-tests and ANCOVA in the 29 subjects who completed the intervention . Results The GI group demonstrated significant reductions in leisure sedentary behavior ( p < .05 ) and increases in moderate physical activity ( p < .05 ) compared to DS group , and a trend toward reduced caloric intake in GI vs DS ( p = .09 ) . Salivary cortisol was acutely reduced by stress-reduction guided imagery ( p < .01 ) . There were no group differences in adiposity , insulin resistance , perceived stress , or stress biomarkers across the 12-week intervention , though decrease in serum cortisol over the course of the intervention was associated with improved insulin sensitivity ( p = .03 ) independent of intervention group and other relevant co-variates . Conclusions The improvements in physical activity and stress biomarkers following this pilot intervention support the role of guided imagery in promoting healthy lifestyle behavior change and reducing metabolic disease risk in obese Latino adolescent population s. Future investigations will be needed to determine the full effects of the Imagine HEALTH intervention on insulin resistance , stress , and stress biomarkers . Trial registration Clinical trials.gov Registry # : Background The prevalence of overweight and obesity in children has at least doubled in the past 25 years with a major impact on health . In 2005 a prevention protocol was developed applicable within Youth Health Care . This study aims to assess the effects of this protocol on prevalence of overweight and health behaviour among children . Methods and design A cluster r and omised controlled trial is conducted among 5-year-old children included by 44 Youth Health Care teams r and omised within 9 Municipal Health Services . The teams are r and omly allocated to the intervention or control group . The teams measure the weight and height of all children . When a child in the intervention group is detected with overweight according to the international age and gender specific cut-off points of BMI , the prevention protocol is applied . According to this protocol parents of overweight children are invited for up to three counselling sessions during which they receive personal advice about a healthy lifestyle , and are motivated for and assisted in behavioural change . The primary outcome measures are Body Mass Index and waist circumference of the children . Parents will complete question naires to assess secondary outcome measures : levels of overweight inducing/reducing behaviours ( i.e. being physically active , having breakfast , drinking sweet beverages and watching television/playing computer games ) , parenting styles , parenting practice s , and attitudes of parents regarding these behaviours , health-related quality of life of the children , and possible negative side effects of the prevention protocol . Data will be collected at baseline ( when the children are aged 5 years ) , and after 12 and 24 months of follow-up . Additionally , a process and a cost-effectiveness evaluation will be conducted . Discussion In this study called ' Be active , eat right ' we evaluate an overweight prevention protocol for use in the setting of Youth Health Care . It is hypothesized that the use of this protocol will result in a healthier lifestyle of the children and an improved BMI and waist circumference . Trial registration Current Controlled Trials IS RCT Objective To determine whether modifying eating behaviour with use of a feedback device facilitates weight loss in obese adolescents . Design R and omised controlled trial with 12 month intervention . Setting Hospital based obesity clinic . Participants 106 newly referred obese young people aged 9 - 17 . Interventions A computerised device , M and ometer , providing real time feedback to participants during meals to slow down speed of eating and reduce total intake ; st and ard lifestyle modification therapy . Main outcome measures Change in body mass index ( BMI ) st and ard deviation score ( SDS ) over 12 months with assessment 18 months after the start of the intervention . Secondary outcomes were body fat SDS , metabolic status , quality of life evaluation , change in portion size , and eating speed . Results Using the last available data on all participants ( n=106 ) , those in the M and ometer group had significantly lower mean BMI SDS at 12 months compared with st and ard care ( baseline adjusted mean difference 0.24 , 95 % confidence interval 0.11 to 0.36 ) . Similar results were obtained when analyses included only the 91 who attended per protocol ( baseline adjusted mean difference 0.27 , 0.14 to 0.41 ; P<0.001 ) , with the difference maintained at 18 months ( 0.27 , 0.11 to 0.43 ; P=0.001 ) ( n=87 ) . The mean meal size in the M and ometer group fell by 45 g ( 7 to 84 g ) . Mean body fat SDS adjusted for baseline levels was significantly lower at 12 months ( 0.24 , 0.10 to 0.39 ; P=0.001 ) . Those in the M and ometer group also had greater improvement in concentration of high density lipoprotein cholesterol ( P=0.043 ) . Conclusions Retraining eating behaviour with a feedback device is a useful adjunct to st and ard lifestyle modification in treating obesity among adolescents . Trial registration Clinical Trials.gov NCT00407420 BACKGROUND AND OBJECTIVE : Most clinic-based weight control treatments for youth have been design ed for preadolescent children by using family-based care . However , as adolescents become more autonomous and less motivated by parental influence , this strategy may be less appropriate . This study evaluated a primary care – based , multicomponent lifestyle intervention specifically tailored for overweight adolescent females . METHODS : Adolescent girls ( N = 208 ) 12 to 17 years of age ( mean ± SD : 14.1 ± 1.4 years ) , with a mean ± SD BMI percentile of 97.09 ± 2.27 , were assigned r and omly to the intervention or usual care control group . The gender and developmentally tailored intervention included a focus on adoptable healthy lifestyle behaviors and was reinforced by ongoing feedback from the teen ’s primary care physician . Of those r and omized , 195 ( 94 % ) completed the 6-month posttreatment assessment , and 173 ( 83 % ) completed the 12-month follow-up . The primary outcome was reduction in BMI z score . RESULTS : The decrease in BMI z score over time was significantly greater for intervention participants compared with usual care participants ( −0.15 in BMI z score among intervention participants compared with −0.08 among usual care participants ; P = .012 ) . The 2 groups did not differ in secondary metabolic or psychosocial outcomes . Compared with usual care , intervention participants reported less reduction in frequency of family meals and less fast-food intake . CONCLUSIONS : A 5-month , medium-intensity , primary care – based , multicomponent behavioral intervention was associated with significant and sustained decreases in BMI z scores among obese adolescent girls compared with those receiving usual care INTRODUCTION The present study describes a r and omised controlled trial ( RCT ) based on a novel , generalisable intervention for childhood obesity , comparing the intervention with a no-treatment control group . METHOD The Malaysian Childhood Obesity Treatment Trial ( MASCOT ) was a single-blind RCT of a dietetic treatment for childhood obesity in children of primary school age ( 7 to 11 years old ) in Kuala Lumpur , Malaysia . The MASCOT comprising eight sessions , of an 8-hour family-centred group treatment programme is described , based on behavioural change techniques . The study sample was characterised by BMI z-score , health related quality of life reported by participants and their parents ( PedsQL question naire ) , objective ly measured habitual physical activity and sedentary behaviour ( Actigraph accelerometry ) RESULTS The MASCOT sample of 107 children was characterised by a low quality of life , mean total score on PedsQL 67.7 ( 4.5 ) as reported by the children , and 66.0 ( 16.4 ) as reported by their parents . The children spent , on average , 89 % of their waking day on sedentary activity , and 1 % of the day in moderate-vigorous intensity physical activity , equivalent to only around 8 minutes/day . CONCLUSION Obese children in the MASCOT study had an impaired quality of life , high levels of sedentary behaviour and very low levels of physical activity OBJECTIVE The objective was to compare targeting increased eating of healthy foods vs. reducing intake of high energy-dense foods within the context of a family-based behavioral weight control program . METHODS AND PROCEDURES Forty-one 8 - 12 year-old children > 85th BMI percentile were r and omly assigned to a 24-month family-based behavioral treatment that targeted increasing fruits and vegetables and low-fat dairy vs. reducing intake of high energy-dense foods . RESULTS Children in the increase healthy food group showed greater reduction in z BMI compared to children in the reduce high energy-dense food group at 12- ( -0.30 z BMI units vs. -0.15 z BMI units , P = 0.01 ) and 24- ( -0.36 z BMI units vs -0.13 z BMI units , P = 0.04 ) month follow-up . Parents in the increase healthy food group showed greater reductions in concern about child weight ( P = 0.007 ) , and these changes were associated with child z BMI change ( P = 0.008 ) . Children in the reduce high energy-dense group showed larger sustained reductions in high energy-dense foods ( P < 0.05 ) . Baseline levels of high energy-dense foods ( P < 0.05 ) , parent food restraint ( P = 0.01 ) , parent concern over parent weight ( P = 0.01 ) and parent acceptance of the child ( P < 0.05 ) moderated child z BMI change , with greater sustained reductions in z BMI for children in the increase healthy food group for each measure . Parent z BMI change followed the same pattern as child changes , and parent and child z BMI changes were correlated ( P < 0.001 ) . DISCUSSION Focusing on healthy food choices within an energy restricted diet may be useful in family-based weight control programs OBJECTIVE To assess the process variables involved in a weight loss program for African-American ad Output:	Conclusions This systematic review identified wide variation in the dose of behavioral interventions to prevent and treat pediatric obesity , but was unable to detect a clear relationship between dose and weight-related outcomes .
MS21366	*TASK* the task is to summarize an input biomedical literature in six sentences *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 summarize the evidence for curative and health enhancement effects through forest therapy and to assess the quality of studies based on a review of r and omized controlled trials ( RCTs ) . Study design A systematic review based on RCTs . Methods Studies were eligible if they were RCTs . Studies included one treatment group in which forest therapy was applied . The following data bases – from 1990 to November 9 , 2010 – were search ed : MEDLINE via PubMed , CINAHL , Web of Science , and Ichushi- Web . All Cochrane data bases and Campbell Systematic Review s were also search ed up to November 9 , 2010 . Results Two trials met all inclusion criteria . No specific diseases were evaluated , and both studies reported significant effectiveness in one or more outcomes for health enhancement . However , the results of evaluations with the CONSORT ( Consoli date d St and ards of Reporting Trials ) 2010 and CLEAR NPT ( A Checklist to Evaluate a Report of a Nonpharmacological Trial ) checklists generally showed a remarkable lack of description in the studies . Furthermore , there was a problem of heterogeneity , thus a meta- analysis was unable to be performed . Conclusion Because there was insufficient evidence on forest therapy due to poor method ological and reporting quality and heterogeneity of RCTs , it was not possible to offer any conclusions about the effects of this intervention . However , it was possible to identify problems with current RCTs of forest therapy , and to propose a strategy for strengthening study quality and stressing the importance of study feasibility and original check items based on characteristics of forest therapy as a future research agenda Objective To compare the pain-reducing effect of forest bathing alone versus forest bathing in combination with stretching and strengthening exercises in patients with chronic posterior neck pain . Methods Sixty-four subjects with posterior neck pain that had lasted more than 3 months were enrolled . They were r and omly divided into a forest bathing alone ( FBA ) group and a forest bathing with exercise ( FBE ) group ; each group included 32 subjects . All subjects from both groups walked every morning in the forest for about 2 hours for 5 days . In the afternoon , the FBE group did a stretching and strengthening exercise for about 4 hours ; the FBA group had free time in the woods . Visual analog scale ( VAS ) on one day , VAS over the previous week , neck disability index ( NDI ) , EuroQol 5D-3L VAS ( EQ VAS ) and index ( EQ index ) , McGill pain question naire ( MPQ ) , the number of trigger points in the posterior neck region ( TRPs ) , and the range of motion of the cervical spine were evaluated on the first and last day of the program and compared between the two groups . Results The number of TRPs were significantly reduced in the FBE group compared with the FBA group ( p=0.013 ) . However , the other scales showed no significant difference between the two groups . Conclusion When patients with chronic posterior neck pain underwent a short-term forest bathing ( less than 7 days ) program , FBE was more effective in the reduction of the number of TRPs than FBA . However , all other pain measurement scales we evaluated showed no statistically significant difference between the two protocol OBJECTIVE To provide scientific evidence supporting the efficacy of forest bathing as a natural therapy for human hypertension . METHODS Twenty-four elderly patients with essential hypertension were r and omly divided into two groups of 12 . One group was sent to a broad-leaved evergreen forest to experience a 7-day/7-night trip , and the other was sent to a city area in Hangzhou for control . Blood pressure indicators , cardiovascular disease-related pathological factors including endothelin-1 , homocysteine , renin , angiotensinogen , angiotensin II , angiotensin II type 1 receptor , angiotensin II type 2 receptor as well as inflammatory cytokines interleukin-6 and tumor necrosis factor α were detected . Meanwhile , profile of mood states ( POMS ) evaluation was used to assess the change of mood state of subjects . In addition , the air quality in the two experimental sites was monitored during the 7-day duration , simultaneously . RESULTS The baselines of the indicators of the subjects were not significantly different . Little alteration in the detected indicators in the city group was observed after the experiment . While subjects exposed to the forest environment showed a significant reduction in blood pressure in comparison to that of the city group . The values for the bio-indicators in subjects exposed to the forest environment were also lower than those in the urban control group and the baseline levels of themselves . POMS evaluation showed that the scores in the negative subscales were lowered after exposure to the forest environment . Besides , the air quality in the forest environment was much better than that of the urban area evidence d by the quantitative detection of negative ions and PM10 ( particulate matter < 10 μm in aerodynamic diameter ) . CONCLUSION Our results provided direct evidence that forest bathing has therapeutic effects on human hypertension and induces inhibition of the renin-angiotensin system and inflammation , and thus inspiring its preventive efficacy against cardiovascular disorders Forest bathing trip is a short , leisurely visit to forest . In this study we determined the health effects of forest bathing trip on elderly patients with chronic obstructive pulmonary disease ( COPD ) . The patients were r and omly divided into two groups . One group was sent to forest , and the other was sent to an urban area as control . Flow cytometry , ELISA , and profile of mood states ( POMS ) evaluation were performed . In the forest group , we found a significant decrease of perforin and granzyme B expressions , accompanied by decreased levels of pro-inflammatory cytokines and stress hormones . Meanwhile , the scores in the negative subscales of POMS decreased after forest bathing trip . These results indicate that forest bathing trip has health effect on elderly COPD patients by reducing inflammation and stress level BACKGROUND Psycho-oncological care , including spiritual care , is essential for cancer patients . Integrated medicine , a therapy combining modern western medicine with various kinds of complementary and alternative medicine , can be appropriate for the spiritual care of cancer because of the multidimensional characteristics of the spirituality . In particular , therapies that enable patients to establish a deeper contact with nature , inspire feelings of life and growth of plants , and involve meditation may be useful for spiritual care as well as related aspects such as emotion . The purpose of the present study was to examine the effect of spiritual care of cancer patients by integrated medicine in a green environment . METHODS The present study involved 22 cancer patients . Integrated medicine consisted of forest therapy , horticultural therapy , yoga meditation , and support group therapy , and sessions were conducted once a week for 12 weeks . The spirituality ( the Functional Assessment of Chronic Illness Therapy-Spiritual well-being ) , quality of life ( Short Form-36 Health Survey Question naire ) , fatigue ( Cancer Fatigue Scale ) , psychological state ( Profile of Mood States , short form , and State-Trait Anxiety Inventory ) and natural killer cell activity were assessed before and after intervention . RESULTS In Functional Assessment of Chronic Illness Therapy-Spiritual well-being , there were significant differences in functional well-being and spiritual well-being pre- and postintervention . This program improved quality of life and reduced cancer-associated fatigue . Furthermore , some aspects of psychological state were improved and natural killer cell activity was increased . CONCLUSIONS It is indicated that integrated medicine performed in a green environment is potentially useful for the emotional and spiritual well-being of cancer patients BACKGROUND Clinical trials have not been reported concerning the health benefits of viewing indoor plants on stress and recovery of surgical patients within a hospital setting . Using various medical and psychologic measurements , this study performed a r and omized clinical trial with surgical patients to evaluate whether plants in hospital rooms have therapeutic influences . METHODS Ninety ( 90 ) patients recovering from a hemorrhoidectomy were r and omly assigned to either control or plant rooms . With half the patients , live plants were placed in their rooms during postoperative recovery periods . Data collected for each patient included length of hospitalization , analgesics used for postoperative pain control , vital signs , ratings of pain intensity , pain distress , anxiety and fatigue , the State-Trait Anxiety Inventory Form Y-1 , the Environmental Assessment Scale , and the Patient 's Room Satisfaction Question naire . RESULTS Viewing plants during the recovery period had a positive influence linking directly to health outcomes of surgical patients . Patients in hospital rooms with plants and flowers had significantly more positive physiologic responses evidence d by lower systolic blood pressure , and lower ratings of pain , anxiety , and fatigue than patients in the control room . Patients with plants also felt more positively about their rooms and evaluated them with higher satisfaction when compared with patients in similar rooms without plants . Based on patients ' comments , plants brightened up the room environment , reduced stress , and also conveyed positive impressions of hospital employees caring for patients . CONCLUSIONS Findings of this study confirmed the therapeutic value of plants in the hospital environment as a noninvasive , inexpensive , and effective complementary medicine for surgical patients . Health care professionals and hospital administrators need to consider the use of plants and flowers to enhance healing environments for patients Objective : This article aim ed to develop the “ forest therapy ” program , which is a cognitive behavior therapy (CBT)-based intervention program using forest environment , and investigate its effects on blood pressure ( BP ) , salivary cortisol , and quality of life ( QoL ) measures in patients with hypertension . Methods : A total of 56 men and women were enrolled for this study , being referred from local health centers in Republic of Korea , from April to October 2009 . They were conveniently assigned to either “ forest ” group participating in the forest therapy program or control group doing self-monitoring of BP . Measurements of salivary cortisol level and QoL were done at initial visits and at 8-week final visits . Results : Both groups did not differ significantly in baseline clinical characteristics . The BP change at week 4 and week 8 did not differ between the two groups . Salivary cortisol level reduction was significantly larger and QoL measures improved significantly more in the forest group at week 8 compared with the control group . Conclusions : The forest therapy program did not induce prolonged systolic blood pressure ( SBP ) reduction . However , considering the significant decrease in cortisol level and improvement in QoL measures , this may be a useful model of community hypertension management program Output:	Conclusion Forest therapy may play an important role in health promotion and disease prevention .
MS21367	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Prior research has suggested that the latent structure of the schizotypy construct ( P. E. Meehl , 1990 ) may be qualitative in nature and have a low base rate ( L. Korfine & M. F. Lenzenweger , 1995 ; M. F. Lenzenweger & L. Korfine , 1992 ) . These studies relied on the application of maximum covariance analysis ( MAXCOV ) to 8 true-false format items from a schizotypy measure . The current study sought to examine the robustness of those prior findings through MAXCOV analysis of fully quantitative measures of schizotypy . Measures of perceptual aberration , magical ideation , and referential thinking were analyzed using MAXCOV in a sample of 429 persons . The results of these analyses strongly support a latent taxonic structure for schizotypy and a low base rate for the schizotypy taxon . Furthermore , the members of the putative taxon reveal an increased level of deviance on a psychometric measure known to be associated with schizophrenia liability . The possibility that the dichotomous item format of those items analyzed previously with MAXCOV lead to spurious pseudotaxonicity is greatly diminished in light of these results Classical descriptions of mania subtypes extend back to Kraepelin ; however , in marked contrast to the study of depression subtypes , validation of mania subtypes by multivariate statistical methods has seldom been attempted . We applied Grade of Membership ( GOM ) analysis to the rated clinical features of 327 in patients with DSM-III-R mania diagnoses . GOM is a type of latent structure multivariate analysis , which differs from others of this type in making no a priori distributional assumptions about groupings . We obtained 5 GOM Pure Types with good face validity . The major Kraepelinian forms of “ hypomania , ” “ acute mania , ” “ delusional mania , ” and “ depressive or anxious mania ” were vali date d. The major new finding is of two mixed mania presentations , each with marked lability of mood . The first of these displayed a dominant mood of severe depression with labile periods of pressured , irritable hostility and paranoia , and the complete absence of euphoria or humor . The second mixed mania Pure Type displayed a true , incongruous mixture of affects : periods of classical manic symptoms with euphoria , elation , humor , gr and iosity , psychosis , and psychomotor activation , switching frequently to moderately depressed mood with pressured anxiety and irritability . This multivariate analysis vali date d classical clinical descriptions of the major subtypes of mania . Two distinct forms of mixed manic episodes were identified . DSM-III-R criteria did not reliably identify either of these two natural groups of mixed bipolar patients . As occurs in depression , this clinical heterogeneity of mania may influence response to drug treatments Objective : To describe patients included in the European Mania in Bipolar Longitudinal Evaluation of Medication ( EMBLEM ) study and to assess and clinical ly vali date the presence of clinical subtypes of patients with acute mania P.E. Meehl 's model ( 1962 , 1990 ) of schizotypy and the development of schizophrenia implies that the structure of liability for schizophrenia is dichotomous , hypothesizing that a " schizogene " determines one 's membership in a latent class ( or taxon ; P.E. Meehl & R. R. Golden , 1982 ) . The present study sought to replicate earlier findings concerning the taxonic latent structure and general population base rate of schizotypy ( M. F. Lenzenweger & L. Korfine , 1992 ) . P.E. Meehl 's ( 1973 ; P.E. Meehl & R. R. Golden , 1982 ) MAXCOV-HITMAX taxometric analytic procedures were applied to a subset of items from the Perceptual Aberration Scale ( PAS ; L. J. Chapman , J. P. Chapman , & M. L. Raulin , 1978 ) , a prominent psychometric index of schizotypy , derived from a new r and omly ascertained non clinical university sample ( N = 1,646 ) . Consistent with the authors ' previous results as well as Meehl 's conjectures , the data strongly suggest that schizotypy , as assessed by the PAS , is taxonic at the latent level with a low general population taxon base rate ( i.e. , < .10 ) . Moreover , individuals falling within the putative schizo-taxon underlying the PAS present greater levels of schizotypic phenomenology than nontaxon members . The taxometric analysis of the psychological trait of femininity also reveals that the MAXCOV-HITMAX procedure can detect a latent dimension , when one is hypothesized to exist , and the procedure does not appear to generate " spurious " evidence for taxonicity as a function of the psychometric format ( e.g. , true-false ) of the data under analysis . The statistical implication of a taxonic entity occurring at a low base is discussed with respect to results obtained using the MAXCOV-HITMAX technique BACKGROUND Several studies have found an association between duration of untreated psychosis ( DUP ) and clinical outcomes . However , there is inconsistency concerning the association between outcome on negative symptoms and DUP with some studies having found a correlation between DUP and negative symptoms , while other studies did not find such an association . OBJECTIVE The aim of the present study was to investigate the role of heterogeneity associated with the relationship between DUP and negative symptoms in a sample of first episode psychosis ( FEP ) patients from a multicentre treatment study and a replication sample of subjects from a specialized service in a different jurisdiction . METHOD FEP patients ( n=116 ) treated in specialized programs in two medium sized and one large urban centre were evaluated . Latent class regression was employed to simultaneously classify respondents and estimate the effect of DUP on negative symptoms after one year . The process was repeated on 59 consecutive FEP patients in a specialized service in Montreal . RESULTS The final model reflected three distinct sub-groups with different associations between DUP and negative symptoms : ( a ) for one fourth of the subjects there was a positive association between DUP and negative symptoms , indicating that long DUP was associated with poor negative symptoms outcome ; ( b ) an opposite effect was observed for another sub-group of patients : patients with short DUP scored high on the negative symptoms scale and patients with long DUP reported only a few negative symptoms ; ( c ) there was no association between DUP and negative symptoms outcome for nearly half of the patients . These models were replicated in the Montreal sample . CONCLUSIONS The association between DUP and negative symptoms outcome might differ among sub-groups of first episode patients . Latent class regression analysis offers a flexible way to include unmeasured heterogeneity in outcome analyses Taxometric procedures such as mean above minus below a cut and maximum covariance can determine whether a trait is distributed as a discrete latent class . These methods have been used to infer taxonic structure in several personality and psychopathology constructs , often from analyses of rating scale data . This is problematic given ( a ) well established biases in ratings , ( b ) the human tendency to think categorically , and ( c ) implicit typological models of personality and psychopathology among expert raters . Using an experimental method in which the cognitive sets of raters were manipulated as dimensional versus categorical , it is demonstrated that pseudotaxonicity can be created readily with rating scale measures . This suggests that research ers avoid an exclusive reliance on rating scales when conducting taxometrics investigations Output:	Virtually all analyses yielded results that , on first impression , favored taxonic over dimensional interpretations of the latent structure of schizophrenia . We conclude that there is no reason to seriously doubt a single-distribution model of schizophrenia because there is no evidence that provides a serious test of this null hypothesis .
MS21368	*TASK* the task is to summarize an input biomedical literature in six sentences *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 performed a r and omized controlled study to evaluate computer-based cognitive behavioral therapy in 36 patients who met Research Diagnostic Criteria for major or minor depression . Patients were r and omly assigned to the computer , to a therapist , or to a control group placed on a waiting list . As determined by three measures of depression ( the Beck inventory , the Hamilton rating scale , and the Symptom Checklist-90-R ) , both treated groups had improved significantly more than the control group at the end of the treatment period and 2 months later . The treated groups did not differ from each other at either time BACKGROUND Counselling in primary care setting s remains largely unevaluated . Such evaluation has been strongly recommended . AIM To determine the relative effectiveness and cost-effectiveness of generic counselling and usual general practitioner ( GP ) care for patients with minor mental health problems . METHOD A r and omized controlled trial and health economic evaluation were carried out in nine general practice s. Access to generic counselling ( brief counselling , generally involving up to six 50-minute sessions ) was compared with usual GP care . A total of 162 patients aged 16 years and over with diverse mental health problems ( excluding phobic conditions and psychoses ) were r and omized . The Hospital Anxiety and Depression ( HAD ) scale , COOP/WONCA ( World Organization of Family Doctors ) functional health assessment charts , and the delighted-terrible faces scale were used to assess outcome four months after r and omization . RESULTS The two groups were similar at baseline . There were significant improvements in both groups between r and omization and follow-up for most outcome measures , but no significant differences between the study arms . The 95 % confidence limits were narrow and excluded clinical ly significant effects . Under various assumptions concerning the cost of secondary care referrals and of counselling time , no clear cost advantage was associated with either intervention . CONCLUSIONS This pragmatic trial demonstrates no difference in functional or mental health outcome at four months between subjects offered access to counselling and those given usual care by their GP . There is no clear difference in the cost-effectiveness of the two interventions . Purchasers should take account of these findings in allocating re sources within primary care Abstract Objective : To compare the clinical effectiveness of general practitioner care and two general practice based psychological therapies for depressed patients . Design : Prospect i ve , controlled trial with r and omised and patient preference allocation arms . Setting : General practice s in London and greater Manchester . Participants : 464 of 627 patients presenting with depression or mixed anxiety and depression were suitable for inclusion . Interventions : Usual general practitioner care or up to 12 sessions of non-directive counselling or cognitive-behaviour therapy provided by therapists . Main outcome measures : Beck depression inventory scores , other psychiatric symptoms , social functioning , and satisfaction with treatment measured at baseline and at 4 and 12 months . Results : 197 patients were r and omly assigned to treatment , 137 chose their treatment , and 130 were r and omised only between the two psychological therapies . All groups improved significantly over time . At four months , patients r and omised to non-directive counselling or cognitive-behaviour therapy improved more in terms of the Beck depression inventory ( mean ( SD ) scores 12.9 ( 9.3 ) and 14.3 ( 10.8 ) respectively ) than those r and omised to usual general practitioner care ( 18.3 ( 12.4 ) ) . However , there was no significant difference between the two therapies . There were no significant differences between the three treatment groups at 12 months ( Beck depression scores 11.8 ( 9.6 ) , 11.4 ( 10.8 ) , and 12.1 ( 10.3 ) for non-directive counselling , cognitive-behaviour therapy , and general practitioner care ) . Conclusions : Psychological therapy was a more effective treatment for depression than usual general practitioner care in the short term , but after one year there was no difference in outcome The aim of this study was to evaluate the effectiveness of 2 methods of administering a cognitive-behavioral self-help program for binge eating disorder . The study was design ed to reproduce many of the conditions that apply in setting s in which self-help interventions are most relevant . Seventy-two women with binge eating disorder were r and omly assigned to 1 of 3 conditions for 12 weeks : pure self-help ( PSH ) , guided self-help ( GSH ) , or a waiting list ( WL ) control condition ( followed by PSH or GSH ) . They were then followed up for 6 months . Both PSH and GSH had a substantial and sustained impact with almost half the participants ceasing to binge eat . There was little change in the WL condition . Cognitive-behavioral self-help may be of value both as an initial treatment for binge eating disorder and as a form of secondary prevention Behavioural methods of treating anxiety have been shown to be highly effective but are not widely available in general practice where most people suffering from anxiety are treated . This study reports a development in service delivery which is simple , inexpensive and does not make great time dem and s on general practitioners or require them to extend their training and expertise . The study shows that for patients suffering from panic disorder or generalized anxiety disorder the use of an anxiety management booklet in addition to their usual treatment from their general practitioner produces clinical ly and statistically significant improvements . Of particular importance is the speed of response to the booklet . Within the first two weeks those patients who received the booklet were significantly less anxious than the controls . The booklet was acceptable to patients and recommendations are made about how to incorporate it into clinical practice The efficacy of a self-help package in treating chronic anxiety was evaluated in a r and omized controlled trial in which the intervention group received self-help material s in the form of an audiotape and booklet , in addition to their current treatment . The intervention was successful in terms of mean depression scores ( P = 0.01 ) , anxiety scores ( P = 0.04 ) and general health question naire scores ( P = 0.02 ) which were significantly lower for the intervention group than for the controls . In addition , the depression scores fell faster for the intervention group than for the controls . The overall mean reduction in three months in adjusted depression scores was approximately two points greater for the intervention group than for the controls ( P = 0.02 ) . Clinicians welcomed the package as a valuable addition to the therapies available for managing chronic anxiety problems . Further studies should include larger sample sizes , taking into account the non-response to postal question naires over time The efficacy of cognitive bibliotherapy for adolescents experiencing mild and moderate depressive symptomatology was examined with a group of 22 community-dwelling adolescents . Cognitive bibliotherapy was determined to be superior to a delayed-treatment control condition . The treatment produced both statistically and clinical ly significant improvements in depressive symptoms . Treatment gains were maintained at 1-month follow-up . A significant decrease in dysfunctional thoughts , but not in negative automatic thoughts , was found after treatment . These results contribute to converging evidence on the efficacy of cognitive-behavioral treatments for adolescents experiencing depressive symptoms A controlled trial study which examined the clinical effectiveness of a stress self-help package administered by general practitioners to patients presenting with psychological problems which were potentially stress-related is described . Patients were r and omly allocated to one of two groups : existing general practitioner treatment with or without the use of the package . Significant advantages were found for patients who received the package compared with controls in both their level of symptoms at three-month follow-up and their rate of consulting for psychological problems in the three-month post-treatment period compared with the three-month pre-treatment period . The potential use of such packages in the treatment of psychological problems in primary care is discussed OBJECTIVE This study assessed relationships among psychological symptoms , past and current psychiatric disorder , functional impairment , somatic symptoms , chronic fatigue , and chronic fatigue syndrome . METHOD A prospect i ve cohort study was followed by a nested case-control study . The subjects , aged 18 - 45 years , had been in primary care for either clinical viral infections or a range of other problems . Question naire measures of fatigue and psychological symptoms were completed by 1,985 subjects 6 months later ; 214 subjects with chronic fatigue were then compared with 214 matched subjects without fatigue . Assessment s were made with question naires , interviews , and medical records of fatigue , somatic symptoms , psychiatric disorder , and functional impairment . RESULTS Subjects with chronic fatigue were at greater risk than those without chronic fatigue for current psychiatric disorder assessed by st and ardized interview ( 60 % versus 19 % ) or by question naire ( 71 % versus 31 % ) . Chronic fatigue subjects were more likely to have received psychotropic medication or experienced psychiatric disorder in the past . There was a trend for previous psychiatric disorder to be associated with comorbid rather than noncomorbid chronic fatigue . Most subjects with chronic fatigue syndrome also had current psychiatric disorder when assessed by interview ( 75 % ) or question naire ( 78 % ) . Both the prevalence and incidence of chronic fatigue syndrome were associated with measures of previous psychiatric disorder . The number of symptoms suggested as characteristics of chronic fatigue syndrome was closely related to the total number of somatic symptoms and to measures of psychiatric disorder . Only postexertion malaise , muscle weakness , and myalgia were significantly more likely to be observed in chronic fatigue syndrome than in chronic fatigue . CONCLUSIONS Most subjects with chronic fatigue or chronic fatigue syndrome in primary care also meet criteria for a current psychiatric disorder . Both chronic fatigue and chronic fatigue syndrome are associated with previous psychiatric disorder , partly explained by high rates of current psychiatric disorder . The symptoms thought to represent a specific process in chronic fatigue syndrome may be related to the joint experience of somatic and psychological distress Output:	There were no data concerning long-term clinical benefits or cost-effectiveness . In conclusion , self-help treatments may have the potential to improve the overall cost-effectiveness of mental health service provision .
MS21369	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Obese children ( 8 - 13 years old ) and at least one of their parents participated in a behaviorally oriented treatment program . Participants in a st and ard treatment condition experienced a multicomponent intervention in which parents were given primary responsibility for following program prescriptions . An enhanced child involvement condition provided the same basic intervention but with greater emphasis on , and training in , child self-regulation . Children in both conditions achieved a significant reduction in percentage overweight and triceps skin-fold during the 6-month treatment period . Overall , the follow-up period of 3 years was characterized by increases above posttreatment levels . There was , however , some suggestion in the 3-year follow-up results and the long-term patterns over a 6 1/2-year period of the benefits of the enhanced child involvement approach . Findings are discussed in terms of suggestions for reconsideration of treatment goals , improved interventions , and refinements in the assessment of self-regulatory behavior Weight and blood pressure changes were evaluated in a 16-month controlled trial comparing three methods of involving mothers in the treatment of their obese adolescents ( aged 12 to 16 years ) . The treatments were : ( 1 ) Mother-Child Separately -- children and mothers attended separate groups ; ( 2 ) Mother-Child Together -- the children and mothers met together in the same group ; and ( 3 ) Child Alone -- the children met in groups and mothers were not involved . The program consisted of behavior modification , social support , nutrition , and exercise . The Mother-Child Separately group lost more weight ( 8.4 kg ) during treatment than did the other two groups ( 5.3 and 3.3 kg ) . Differences between the groups increased at the 1-year follow-up : compared to pretreatment weight , the Mother-Child Separately group lost 7.7 kg compared with gains of approximately 3 kg in the other two groups . Blood pressures of children with the highest initial pressures decreased by 16/9 mm Hg at the end of treatment and by 16/5 mm Hg at the 1-year follow-up . These results suggest that a program of behavior modification and parent involvement can lead to significant weight losses in obese children , and that the nature of parent involvement may be important Two types of goal - setting ( daily vs weekly ) and two levels of spouse involvement ( couples vs individual treatment ) were evaluated in a 19-week behavioral weight-control program . Forty-seven married Ss with spouses willing to participate were r and omly assigned to one of four treatments : Couples/Weekly Goals , Couples/Daily Goals , Individual/Weekly Goals , Individual/Daily Goals . At posttreatment , Ss had lost an average of 171b and reduced their percent over ideal weight from 49 to 36 % . Losses were maintained at the 6-month clinic follow-up . Weight losses for the two goal - setting conditions and the two spouse treatments did not differ . Improvements were observed in resting pulse , blood pressure and step-test time , and these were maintained at the 6-month follow-up . Adherence to caloric self-monitoring , self-reported exercise adherence and marital satisfaction were significantly correlated with weight loss . Decreases in depression and improvements in body-image satisfaction were also observed . Mail and telephone follow-up at 12 and 30 months posttreatment indicated satisfactory maintenance for the majority of Ss . Factors associated with maintenance and relapse during long-term follow up are discussed STUDY OBJECTIVE To evaluate the effect of family therapy on childhood obesity . DESIGN Clinical trial . One year follow-up . SETTING Referral from school after screening . PARTICIPANTS Of 1774 children ( aged 10 to 11 ) , screened for obesity , 44 obese children were divided into two treatment groups . In an untreated control group of 50 obese children , screened in the same manner , body mass index ( BMI ) values were recorded twice , at 10 to 11 and at 14 years of age . INTERVENTION Both treatment groups received comparable dietary counseling and medical checkups for a period of 14 to 18 months , while one of the groups also received family therapy . RESULTS At the 1-year follow-up , when the children were 14 years of age , intention-to-treat analyses were made of the weight and height data for 39 of 44 children in the two treatment groups and for 48 of the 50 control children . The increase of BMI in the family therapy group was less than in the conventional treatment group at the end of treatment , and less than in the control group ( P = .04 and P = .02 , respectively ) . Moreover , mean BMI was significantly lower in the family therapy group than in the control group ( P < .05 ) , and the family therapy group also had fewer children with BMI > 30 than the control group ( P = .02 ) . The reduction of triceps , subscapular , and suprailiac skinfold thicknesses , expressed as percentages of the initial values , was significantly greater in the family therapy group than in the conventional treatment group ( P = .03 , P = .005 and P = .002 , respectively ) , and their physical fitness was significantly better ( P < .05 ) . CONCLUSIONS Family therapy seems to be effective in preventing progression to severe obesity during adolescence if the treatment starts at 10 to 11 years of age Abstract The present study was conducted to determine if husb and attendance at treatment sessions and participation in behavioral contracting would produce greater weight losses than two other levels of spouse involvement . The three treatment groups investigated did not significantly differ at post-treatment but by 1-yr follow-up female S s who attended treatment sessions alone and contracted with the counselor ( HA ) lost significantly more weight than women who attended sessions with their husb and s and also contracted with the counselor ( HNC ) . The S s who attended sessions with their husb and s and contracted with them ( HC ) did not significantly differ from S s in the other two conditions . The total amount lost by S s in the HA , HNC and HC conditions by 1-yr follow-up was 16.4 , 4.4 and 15.5 lb , respectively . The study was also conducted to collect preliminary data about procedures S s used during long-term follow-up to ascertain if weight losses during follow-up could be attributed to the behavioral weight-loss techniques learned during the treatment program . At all follow-up periods , many S s reported using behavioral weight-loss techniques but 4 of the 36 S s ( 11.1 % ) at 1-yr follow-up , 15 of the 23 ( 65.2 % ) and 24 of the 25 ( 96.0 % ) who responded , respectively , at 3- and 4-yr follow-up had used other weight-loss programs or methods . A possible confound for follow-up data was identified and suggestions for future research were presented OBJECTIVE To compare the effectiveness of behavioral family systems therapy ( BFST ) with that of ego-oriented individual therapy ( EOIT ) as treatments for adolescents with anorexia nervosa . METHOD Thirty-seven adolescents meeting DSM-III-R criteria for anorexia nervosa were r and omly assigned to receive BFST or EOIT , in addition to a common medical and dietary regimen . In BFST , the family was seen conjointly , the parents were placed in control of the adolescent 's eating , distorted beliefs were targeted through cognitive restructuring , and strategic/behavioral interventions were used to change family interactions . In EOIT , the adolescent was seen individually , with an emphasis on building ego strength and uncovering the dynamics blocking eating ; parents were seen collaterally . Measures administered before , after , and at 1-year follow-up tapped body mass index , menstruation , eating attitudes , ego functioning , depression , and family interactions . RESULTS BFST produced greater weight gain and higher rates of resumption of menstruation than EOIT . Both treatments produced comparably large improvements in eating attitudes , depression , and eating-related family conflict , but very few changes occurred on ego functioning . CONCLUSIONS BFST and EOIT proved to be effective treatments for adolescents with anorexia nervosa , but BFST produced a faster return to health Using a prospect i ve , r and omized , controlled design , we examined the effects of behavioral family-based treatment on percent overweight and growth over 10 years in obese 6- to 12-year-old children . Obese children and their parents were r and omized to three groups that were provided similar diet , exercise , and behavior management training but differed in the reinforcement for weight loss and behavior change . The child and parent group reinforced parent and child behavior change and weight loss , the child group reinforced child behavior change and weight loss , and the nonspecific control group reinforced families for attendance . Children in the child and parent group showed significantly greater decreases in percent overweight after 5 and 10 years ( -11.2 % and -7.5 % , respectively ) than children in the nonspecific control group ( + 7.9 % and + 14.3 % , respectively ) . Children in the child group showed increases in percent overweight after 5 and 10 years ( + 2.7 % and + 4.5 % , respectively ) that were midway between those for the child and parent and nonspecific groups and not significantly different from either . At 10 years , child height was related strongly to the height of the parent of the same sex ( r = .78 children were 1.8 cm taller than their parents , with no differences in height between groups This study tested the effects of mastery criteria and contingent reinforcement in a family-based behavioral weight control program for obese children and their parents over two years . Families with obese children were r and omized to one of two groups . The experimental group was targeted and reinforced for mastery of diet , exercise , weight loss , and parenting skills . The control group was taught behavior-change strategies and provided noncontingent reinforcement at a pace yoked to the experimental group . Both groups received the same behavioral family-based educational components over 6 months of weekly meetings and six monthly follow-up meetings . Results showed significantly better relative weight change at 6 months and 1 year for children in the experimental compared to the control group , but these effects were not maintained at 2 years . These results suggest the introduction of mastery criteria and contingent reinforcement for mastery can improve outcome during treatment in behavioral treatments for childhood obesity Forty-nine obese diabetic patients with obese spouses ( diabetic or nondiabetic ) were r and omly assigned to an alone or together condition . Patients in the alone group participated by themselves in a 20-week behavioral weight control program ; their spouses attended assessment sessions only . Patients in the together group attended the program with their spouses ; both were targeted for weight loss and taught social support strategies . Weight losses of patients treated alone and together did not differ significantly at posttreatment ( 19.9 vs. 19.1 lb ) or 1-year follow-up ( 11.6 vs. 7.0 lb ) . However , there was a significant interaction of treatment and gender ; women did better when treated with their spouses , whereas men did better when treated alone . A " family-based " approach was not effective for these obese Type II diabetic patients as a whole but may be helpful for women This study investigated whether husb and participation would augment the effectieness of the Sturart & Davis ( 1972 ) weight-reduction program for 37 obese women . Following a five-week baseline period , participants were taught behavioral weight-control techniques in eight 90-minute sessions over a 16-week period . R and om assignment was made to conditions that required husb and s to participate in all treatment sessions , the first four sessions , or not at all . Results indicated that although women in all three conditions lost significant amounts of weight and developed more adaptive eating habits , husb and involvement fostered reliably greater weight loss , which was maintained through a six-week post-treatment assessment . Participant husb and s became more accurate observers of changes in their wives ' eating habits and were viewed as being more helpful than were noninvolved husb and s. A three-year follow-up indicated that the wives had maintained their initial weight losses and reported changes in eating habits , while the effects engendered by husb and involvement had dissipated Two groups of cerebral palsied , mentally retarded , overweight adults received training in seven behavioral self-control techniques for reducing caloric intake and increasing activity levels over the course of 19 weeks . One group 's parents/caretakers had frequent contacts from the diet leader , ( Home-Help Group ) ; the other group , balanced with the first for degree of h and icap , had no caretaker-directed communications other than initial notification ( No Help Group ) . Measures of adherence were included to assess the process of behavioral change during the diet program . A significant treatment effect accrued for all participants in the diet program , with the Home-Help Group of dieters showing clinical ly , though not statistically superior weight loss at treatment end and at follow-ups through one year . Specific behaviors taught , such as replacing utensils after each bite and eating slowly , showed significant changes in the expected directions with weight change . Implication s of the data for future treatment programs are discussed Output:	There was a suggestion that spouse involvement increased effectiveness but that adolescents achieved greater weight loss when treated alone . In studies including children , beneficial effects were seen when greater numbers of behaviour change techniques were taught to both parents and children . : Relatively few intervention studies exist in this important area , particularly studies targeting adolescents , and they highlight continued uncertainty about how best to involve family members . The studies provide limited support for the involvement of spouses . They suggest that parental involvement is associated with weight loss in children , and that use of a greater range of behaviour change techniques improves weight outcomes for both parents and children .
MS21370	*TASK* the task is to summarize an input biomedical literature in six sentences *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 identify factors that have contributed to reduced rates of death and complications after esophageal resection in a 17-year period at a tertiary referral center . Summary Background Data There has been an evolving refinement in surgical technique and perioperative management of patients undergoing esophageal resection at Queen Mary Hospital during the past two decades . As of the end of 1998 , there had been no hospital deaths among the last 105 consecutive resections performed for esophageal squamous cancer . Methods The results of esophageal resection for squamous cell carcinoma were analyzed using a prospect i ve esophageal data base . A longitudinal study was performed to compare and analyze rates of death and complications for three consecutive time periods . Results The study group comprised 710 patients who underwent one-stage esophageal resection between 1982 and 1998 . A transthoracic esophagectomy was the preferred approach in 590 patients ( 83 % ) . The overall hospital death rate was 11 % . The leading causes of hospital death were pulmonary complications ( 45.5 % ) and progression of malignant disease ( 21.5 % ) ; anastomotic leakage accounted for 9 % of deaths . During the study period , the hospital death rate decreased from 16 % to 3.2 % , and the incidence of postoperative respiratory failure decreased from 15.5 % to 6.5 % . Perioperative factors that correlated with the decreased death rate over time were the increased postoperative use of epidural analgesia and bronchoscopy ( for clearance of pulmonary secretions ) , a decrease in history of smoking , and a decrease in surgical blood loss of more than 1,000 mL. Conclusions In this series of predominantly transthoracic esophagectomies , there has been a decline in the hospital death rate to less than 5 % . These results are largely attributable to factors aim ed at reducing postoperative pulmonary complications Background We clarified the incidence of adenocarcinoma of the esophagogastric junction ( AEG ) at a Japanese high-volume cancer center and its clinicopathological features between the Siewert subtypes . Methods Patients with AEG were selected from a prospect i ve data base of gastric and esophageal tumors established by Kanagawa Cancer Center . The Siewert subtypes were determined retrospectively by examining pathological pictures of the resected specimens and by evaluating the pathology and endoscopy findings . Results From January 1986 to December 2005 , 147 ( 4.0 % ) patients were determined to have AEG ; 2,794 ( 75.8 % ) were diagnosed to be true gastric cancer , whereas 745 ( 20.2 % ) were true esophageal cancer . Of these 147 patients with AEG , 5 ( 3.4 % ) were classified as type I , 82 ( 55.8 % ) as type II , and 60 ( 40.8 % ) as type III tumors . The depth of tumor invasion was deeper and the nodal metastases were more frequent in type III compared with type II . The risk factors for nodal metastases included the depth and size of the tumor , but not the Siewert subtypes itself . Mediastinal nodal metastases were strongly influenced by a thoracotomy and the extent of the dissection . The pathological grade was higher in type III than in type II . Although the 5-year survival rate was significantly higher in type II than in type III tumors , the survival difference disappeared when the patients were restricted to an R0 resection , even though type III patients demonstrated a more advanced stage . Conclusions The proportions of AEG were strikingly different between Japan and western countries . Although each Siewert subtype had some different characteristics , nodal metastases were determined by both the tumor progression and the extent of the nodal dissection . An R0 resection was a key for the survival in AEG Purpose : To investigate the importance of lymph node yield ( LNY ) and the ratio of afflicted lymph nodes in esophageal carcinoma patients . Patients and Methods : Between 1992 and 2004 , 368 patients with esophageal carcinoma underwent surgery . Esophagectomy with curative intent was performed in 255 patients . Subtotal esophagectomy was performed either by thoracoabdominal ( 104 patients , 40.8 % ) or by transhiatal approach ( 151 patients , 59.2 % ) . Results : According to the LNY , patients were grouped into 3 groups . Twenty-six patients had ≤5 , 96 had 6 to 18 , and 113 had ≥19 dissected lymph nodes . In patients with nodal involvement ( pN1 ) , no significant overall survival differences were identified when stratifying subgroups according to the LNY . However , LNY had striking prognostic relevance in pN0 patients . The median overall survival was 23 ( ≤5 LN ) , 36 ( 6–18 LN ) , and 88 months ( ≥19 ) . Even for patients with tripled LNY than the proposed minimum by the International Union Against Cancer ( UICC ) ( 18 LN ) , the rate of patients with detected lymph node metastases was only 46 % , compared with 61 % for patients with a LNY of ≥19 ( P = 0.002 ) . In pN1 patients classified according to the ratio of afflicted lymph nodes , median overall survival was 27 months in patients with a ratio < 11 % , compared with 15 and 13 months in patients with a ratio of 11 % to 33 % and > 33 % , respectively ( P < 0.001 ) . Multivariate Cox regression modeling identified ratio as the strongest independent prognostic factor for overall survival in pN1 and the LNY in pN0 patients . Conclusions : The minimal regional LNY of 6 lymph nodes as recommended by the UICC for esophageal carcinoma is far too low to appropriately stage the disease . The LNY and the ratio should be reflected in the next version of the UICC classification OBJECTIVE To study survival , morbidity , and ability to swallow , after oesophagectomy for cancer of the oesophagus and cardia . DESIGN Prospect i ve open study . SETTING University hospital , Norway . SUBJECTS 83 patients , 38 with squamous cell carcinoma and 45 with adenocarcinoma of the oesophagus and cardia . INTERVENTIONS Transhiatal ( n = 51 ) and transthoracic ( n = 32 ) oesophagectomy . Oesophageal replacement was by either stomach ( n = 80 ) or colon ( n = 3 ) . Cervical anastomosis was used in all but 2 . MAIN OUTCOME MEASURES Early and late morbidity and mortality , length of stay in intensive care unit and in hospital , and survival analysis . RESULTS 30 Day and in hospital mortality were 0 and 4 % for transhiatal , and 6 % and 9 % for transthoracic , oesophagectomy . Complications included recurrent nerve palsy ( n = 7 ) , anastomotic leaks ( n = 5 ) , and chylothorax ( n = 4 ) . 17 Patients ( 22 % ) needed dilatations for stenosis of the anastomosis , and 71 ( 85 % ) of the patients left hospital within four weeks of operation . Survival analysis showed a 5 year survival rate of 33 % for patients with adenocarcinoma operated on for cure and a 2 year survival of 28 % for patients with squamous cell carcinoma . CONCLUSIONS Oesophagectomy for cure is worthwhile as some patients are cured and most of the remainder have prolonged relief of their dysphagia . Palliative resections should not be done in patients with distant metastases or invasion of adjacent organs by the tumour because of long stay in hospital , appreciable morbidity , and short life expectancy Objective : “ Rediscovered ” in 1976 , transhiatal esophagectomy ( THE ) has been applicable in most situations requiring esophageal resection and reconstruction . The objective of this study was to review the authors ’ 30-year experience with THE and changing trends in its use . Methods : Using the authors ’ prospect i ve Esophagectomy Data base , this single institution experience with THE was analyzed retrospectively . Results : Two thous and and seven THEs were performed—1063 ( previously reported ) between 1976 and 1998 ( group I ) and 944 from 1998 to 2006 ( group II ) , 24 % for benign disease , 76 % , cancer . THE was possible in 98 % . Stomach was the esophageal substitute in 97 % . Comparing outcomes between group I and group II , statistically significant differences ( P < 0.001 ) were observed in hospital mortality ( 4 % vs. 1 % ) ; adenocarcinoma histology ( 69 % vs. 86 % ) ; use of neoadjuvant chemoradiation ( 28 % vs. 52 % ) ; mean blood loss ( 677 vs. 368 mL ) ; anastomotic leak ( 14 % vs. 9 % ) ; and discharge within 10 days ( 52 % vs. 78 % ) . Major complications remain infrequent : wound infection/dehiscence , 3 % , atelectasis/pneumonia , 2 % , intrathoracic hemorrhage , recurrent laryngeal nerve paralysis , chylothorax , and tracheal laceration , < 1 % each . Late functional results have been good or excellent in 73 % . Aggressive preoperative conditioning , avoiding the ICU , improved pain management , and early ambulation reduce length of stay , with 50 % in group II discharged within 1 week . Conclusion : THE refinements have reduced the historic morbidity and mortality of esophageal resection . This largest reported THE experience reinforces the value of consistent technique and a clinical pathway in managing these high acuity esophageal patients Objective : Using Worldwide Esophageal Cancer Collaboration data , we sought to ( 1 ) characterize the relationship between survival and extent of lymphadenectomy , and ( 2 ) from this , define optimum lymphadenectomy . Summary Background Data : What constitutes optimum lymphadenectomy to maximize survival is controversial because of variable goals , analytic methodology , and generalizability of the underpinning data . Methods : A total of 4627 patients who had esophagectomy alone for esophageal cancer were identified from the Worldwide Esophageal Cancer Collaboration data base . Patient-specific risk-adjusted survival was estimated using r and om survival forests . Risk-adjusted 5-year survival was averaged for each number of lymph nodes resected and its relation to cancer characteristics explored . Optimum number of nodes that should be resected to maximize 5-year survival was determined by r and om forest multivariable regression . Results : For pN0M0 moderately and poorly differentiated cancers , and all node-positive ( pN+ ) cancers , 5-year survival improved with increasing extent of lymphadenectomy . In pN0M0 cancers , no optimum lymphadenectomy was defined for pTis ; optimum lymphadenectomy was 10 to 12 nodes for pT1 , 15 to 22 for pT2 , and 31 to 42 for pT3/T4 , depending on histopathologic cell type . In pN+M0 cancers and 1 to 6 nodes positive , optimum lymphadenectomy was 10 for pT1 , 15 for pT2 , and 29 to 50 for pT3/T4 . Conclusions : Greater extent of lymphadenectomy was associated with increased survival for all patients with esophageal cancer except at the extremes ( TisN0M0 and ≥7 regional lymph nodes positive for cancer ) and well-differentiated pN0M0 cancer . Maximum 5-year survival is modulated by T classification : resecting 10 nodes for pT1 , 20 for pT2 , and ≥30 for pT3/T4 is recommended CONTEXT Hospitals that treat a relatively high volume of patients for selected surgical oncology procedures report lower surgical in-hospital mortality rates than hospitals with a low volume of the procedures , but the reports do not take into account length of stay or adjust for case mix . OBJECTIVE To determine whether hospital volume was inversely associated with 30-day operative mortality , after adjusting for case mix . DESIGN AND SETTING Retrospective cohort study using the Surveillance , Epidemiology , and End Results (SEER)-Medicare linked data base in which the hypothesis was prospect ively specified . Surgeons determined in advance the surgical oncology procedures for which the experience of treating a larger volume of patients was most likely to lead to the knowledge or technical expertise that might offset surgical fatalities . PATIENTS All 5013 patients in the SEER registry aged 65 years or older at cancer diagnosis who underwent pancreatectomy , esophagectomy , pneumonectomy , liver resection , or pelvic exenteration , using incident cancers of the pancreas , esophagus , lung , colon , and rectum , and various genitourinary cancers diagnosed between 1984 and 1993 . MAIN OUTCOME MEASURE Thirty-day mortality in relation to procedure volume , adjusted for comorbidity , patient age , and cancer stage . RESULTS Higher volume was linked with lower mortality for pancreatectomy ( P=.004 ) , esophagectomy ( P<.001 ) , liver resection ( P=.04 ) , and pelvic exenteration Output:	There was no difference in blood loss . Analysis of 5-year survival showed no significant difference between the groups and was subject to significant heterogeneity . This meta- analysis of studies comparing transthoracic with transhiatal esophagectomy for cancer demonstrates no difference in 5-year survival , however lymphadenectomy and reported surgical quality was suboptimal in both groups and the transthoracic group had significantly more advanced cancer .
MS21371	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background A prospect i ve study including 272 patients with suspected appendicitis was performed . The aims were to evaluate the representativity of the study group and to compare diagnostic and therapeutic laparoscopy with conventional appendicectomy Abstract . A prospect i ve , r and omized trial was performed to compare open appendectomy with laparoscopic appendectomy in men with a clinical diagnosis of acute appendicitis . Sixty-four patients with a median age of 25 years ( range 18–84 years ) were r and omized to open appendectomy ( n = 31 ) or laparoscopic ( n = 33 ) appendectomy . Of the 64 men , 56 ( 87.5 % ) had appendicitis ( 27 open , 29 laparoscopic procedures ) . The mean operating times were 50.6 ± 3.7 minutes ( ± SEM ) for open and 58.9 ± 4.0 minutes for laparoscopic appendectomy ( p = 0.13 ) . Five ( 15 % ) patients r and omized to laparoscopic appendectomy had an open operation . The mean postoperative hospital stay was significantly longer for open appendectomy ( 3.8 ± 0.4 days ) than for laparoscopic appendectomy ( 2.9 ± 0.3 days ) ( t = 2.05,df = 62,p = 0.045 ) . The complication rate after open appendectomy ( 25.8 % ) was not significantly different from that after laparoscopic appendectomy ( 12.1 % ) . There was a single postoperative death due to a pulmonary embolus in the laparoscopic group and a single death due to cardiac and renal failure in the open group . The mean time to return to normal activities was significantly longer following open appendectomy ( 19.7 ± 2.4 days ) than after laparoscopic appendectomy ( 10.4 ± 0.9 days ) , ( t = 3.75,df = 49,p = 0.001 ) . In conclusion , laparoscopic appendectomy in men has significant advantages in terms of a more rapid recovery compared to open appendectomy . There were no significant disadvantages to laparoscopic appendectomy compared to open appendectomy Aim : To see whether laparoscopy improves the accuracy of a clinical diagnosis of acute appendicitis in women of reproductive age , and to determine what the long-term sequelae are of not removing an appendix deemed at laparoscopy to be normal . Method : The initial part of the study was undertaken during 1991–1992 . Female patients between 16 and 45 years were eligible for inclusion once a clinical decision had been made to perform an appendicectomy for suspected acute appendicitis . Following consent , patients were r and omized into two groups . One group had open appendicectomy , as planned . The other group had laparoscopy , followed by open appendicectomy only if the appendix was seen to be inflamed or was not visualized . The end points for the study were the clinical outcomes of all patients , and the results of histology , where appropriate . An attempt was made to contact all patients at 10 years to determine whether they had had a subsequent appendicectomy , or had been diagnosed with another abdominal condition that might be relevant to the initial presentation in 1991–1992 . Results : Laparoscopic assessment was correct in all cases in which the appendix was visualized . Diagnostic accuracy was improved from 75 % to 97 % . Laparoscopy was associated with no added complications , no increase in hospital stay in patients who went on to appendicectomy , and a reduction in hospital stay for those who underwent laparoscopy alone . No patients developed a problem over the 10-year follow-up period from having a normal-looking appendix not removed at laparoscopy . Conclusion : Laparoscopic assessment of the appendix is reliable , and to leave a normal-looking appendix at laparoscopy does not appear to cause any long-term problems INTRODUCTION The aim of the study is to analyse the own data and try to discuss if laparoscopic appendectomy offers any advantages in treating young women suffering from pain in right lower abfdominal quadrant . MATERIAL S AND METHODS The study was conducted on 148 patients admitted from October 1993 to December 1998 with diagnosis of of pain in right iliac fossa and operated on with a laparoscopic ( LA group : 75 cases ) or open approach ( OA group : 73 cases ) . Patients were prospect ively r and omized on the surgical approach adopted , following a r and omized list . RESULTS The operative time in LA group was significantly ( p < 0.001 ) longer ( 87.2 minutes ) than for OA group ( 65.2 minutes ) . In 2 patients ( 2.7 % ) the operation had to be converted . Diagnosis had remained unknown in 16 patients ( 21.9 % ) of OA group , in spite of only one case ( 1.4 % ) with laparoscopic technique . We did n't observed intraoperative complications . Pain in the first and second postoperative days , evaluated on the use of pain medication , was significantly less in patients in group LA ( p < 0.01 ) . There were no deaths . Postoperative complications occurred in 4 patients ( 5.5 % ) of group LA , and in 8 patients ( 10.9 % ) of group OA . Hospital stay was significantly shorter for those having laparoscopic appendectomy ( p < 0.001 ) . DISCUSSION The main advantages of laparoscopic appendectomy consist more in diagnostic accuracy , than in less postoperative pain , less hospital stay and less postoperative complications . CONCLUSION Laparoscopic appendectomy is a safe and accurate approach The benefits of laparoscopic appendectomy appear to be controversial . Since 1994 , several abdominal procedures have been completed by using the needlescopic technique , but there appear to be no prospect i ve studies to demonstrate the perceived benefits of needlescopic appendectomy . The authors compared open , laparoscopic , and needlescopic appendectomy in a r and omized fashion with regard to duration of surgery , length of hospitalization , analgesic dosage , and surgery-associated complications . From March to July 1998 , 75 patients admitted at the emergency station of the authors ' hospital with a final diagnosis of acute appendicitis without tumor formation were r and omized to receive one of the three treatment categories : open ( OA ) , laparoscopic ( LA ) , and needlescopic ( nLA ) appendectomy . Laparoscopic and needlescopic appendectomy were performed by using a three-port technique , although the size of the trocar used varied . There were 26 patients in the OA group , 23 in the LA group , and 26 in the nLA group . The mean operation duration s for the OA , LA , and nLA groups were 55.4 ± 28.0 minutes , 69.1 ± 48.8 minutes , and 62.3 ± 26.3 minutes , respectively , and these were not significantly different from one another . The mean number of the analgesic doses ( Pethidine 1 mg/kg ) required was 1.3 ± 1.2 mg/kg , 0.5 ± 0.8 mg/kg , and 0.2 ± 0.6 mg/kg , respectively . Significant differences were noted when comparing the OA with the LA or nLA groups ( OA vs. LA , P = 0.02 ; OA vs. nLA , P = 0.0002 ; LA vs. nLA , P = 0.06 ) . The mean oral intake duration s were 32.2 ± 16.9 hours , 21.0 ± 14.6 hours , and 20.8 ± 16.4 hours , respectively , after surgery for the OA , LA , and nLA groups , and the between-group differences were statistically significant for the OA versus LA group ( P = 0.004 ) and for the OA versus nLA group ( P = 0.003 ) . The mean duration s of hospitalization for the OA , LA , and nLA groups were 3.6 ±1.8 days , 2.8 ± 1.4 days , and 2.4 ± 0.9 days , and difference was detected between the OA and the nLA groups ( P = 0.02 ) . The OA group rendered a greater wound-complication rate and ileus than did the other two groups , but the differences were not detected between the three categories ( P = 0.065 , 0.6935 ) . The result of the current study confirmed that the nLA procedure is a feasible and safe one . The nLA procedure provided substantial advantages over the OA procedure in the context s of diminished postoperative pain and shorter hospital stay without significant increases in postoperative complication rate or surgical time BACKGROUND Laparoscopic appendectomy is feasible , but whether it confers any advantage to patients with acute appendicitis is not known . We performed a r and omized controlled trial to compare results of laparoscopic and open appendectomy in patients with signs and symptoms suggesting acute appendicitis who were seen by one surgical team . METHODS Sixty-two consecutive patients were r and omized , 30 to laparoscopy and 32 to a classical open appendectomy . Postoperative recovery , complications , and return to normal activities were compared in the two groups . RESULTS The laparoscopy group were discharged earlier ( 2.5 vs 3.8 days , p less than 0.01 ) . Postoperative complications were more frequent after open appendectomy . Follow-up showed less pain , shorter bed stay at home , and faster return to work and sport after laparoscopic appendectomy . CONCLUSIONS This prospect i ve r and omized study shows that laparoscopic appendectomy is superior to open appendectomy in terms of hospital stay , postoperative complications , and return to normal activities and is recommended as the approach of choice in the management of acute appendicitis Hyperkalaemia with ECG changes had been noted during prolonged carbon dioxide pneumoperitoneum in pigs . We have compared plasma potassium concentrations during surgery in 11 patients allocated r and omly to undergo either laparoscopic or open appendectomy and in another 17 patients allocated r and omly to either carbon dioxide pneumoperitoneum or abdominal wall lifting for laparoscopic colectomy . Despite an increasing metabolic acidosis , prolonged carbon dioxide pneumoperitoneum result ed in only a slight increase in plasma potassium concentrations , which was both statistically and clinical ly insignificant . Thus hyperkalaemia is unlikely to develop in patients with normal renal function undergoing carbon dioxide pneumoperitoneum for laparoscopic surgery Background The aim of this study was to study the value of diagnostic laparoscopy prospect ively in fertile women scheduled for acute appendectomy . Methods For this study , 110 women , with acute abdominal pain ages 15 to 47 years , in whom the surgeon had decided to perform an appendectomy , were r and omized to either open appendectomy or diagnostic laparoscopy , then open appendectomy if necessary . Results Appendicitis was diagnosed in 66 % of the women after open surgery , and in 73 % after laparoscopy . During laparoscopy , was appendicitis misdiagnosed in only 7 % of the women , from whom the appendix unnecessarily removed , whereas 34 % in the open surgery group had a healthy appendix removed . No appendicitis was missed in the laparoscopic group . The relative risk of removing a healthy appendix in open surgery was 6.6 relative risk ( range , 2–21 C.I. ) as compared with laparoscopy . Among the women with a healthy appendix , a gynecologic diagnosis was found in 73 % after laparoscopy , as compared with 17 % after open surgery . Conclusions Laparoscopy reduces unnecessary appendectomies and improves diagnosis in fertile women BACKGROUND Laparoscopic appendectomy has now gained wider acceptance in clinical practice , particularly in the treatment of women with right iliac fossa pain . However , the precise role of laparoscopic appendectomy in men is unclear , and this study was therefore undertaken to examine this specific issue in a prospect i ve r and omized trial . METHODS One hundred men between the ages of 16 and 65 years who had suspected appendicitis were recruited and r and omized to undergo either open or laparoscopic appendectomy . Both groups were compared in terms of their clinical parameters , duration of anesthetic and operation times , postoperative pain , duration of ileus , and length of hospital stay . RESULTS The histologic confirmation of appendicitis was present in 94 % of the cases for both groups of patients . Laparoscopic appendectomy required significantly longer anesthetic time ( 72.5 minutes versus 55 minutes ) and actual operating time ( 45 minutes versus 25 minutes ) compared with open appendectomy . Postoperative pain as measured by visual analog scale on postoperative days 1 and 2 were not significantly different between the patients who underwent laparoscopic and open surgery with values of 4.7 versus 4.4 and 2.1 versus 2.2 , respectively . Also no significant difference was seen between the laparoscopic and open appendectomy groups in the recovery of bowel function ( 24.7 hours versus 21 hours ) and in the length of hospital stay ( 4.9 days versus 5.3 days ) . CONCLUSIONS The results of this prospect i ve r and omized trial showed that there were no significant advantages of laparoscopic appendectomy over open appendectomy for the treatment of male patients with suspected appendicitis . We recommend that the use of laparoscopy Output:	We found that laparoscopy in women with acute lower abdominal pain , non-specific lower abdominal pain or suspected appendicitis led to a higher rate of specific diagnoses being made and a lower rate of removal of normal appendices compared with open appendicectomy only . Hospital stays were shorter . No evidence showed an increase in adverse events when any of these strategies were used
MS21372	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Abstract A four-month , double-blind , crossover study of 22 patients with familial Mediterranean fever was undertaken to study the effect of colchicine in decreasing acute attacks of that disease . T Background Supporting 21st century health care and the practice of evidence -based medicine ( EBM ) requires ubiquitous access to clinical information and to knowledge-based re sources to answer clinical questions . Many questions go unanswered , however , due to lack of skills in formulating questions , crafting effective search strategies , and accessing data bases to identify best levels of evidence . Methods This r and omized trial was design ed as a pilot study to measure the relevancy of search results using three different interfaces for the PubMed search system . Two of the search interfaces utilized a specific framework called PICO , which was design ed to focus clinical questions and to prompt for publication type or type of question asked . The third interface was the st and ard PubMed interface readily available on the Web . Study subjects were recruited from interns and residents on an inpatient general medicine rotation at an academic medical center in the US . Thirty-one subjects were r and omized to one of the three interfaces , given 3 clinical questions , and asked to search PubMed for a set of relevant articles that would provide an answer for each question . The success of the search results was determined by a precision score , which compared the number of relevant or gold st and ard articles retrieved in a result set to the total number of articles retrieved in that set . Results Participants using the PICO templates ( Protocol A or Protocol B ) had higher precision scores for each question than the participants who used Protocol C , the st and ard PubMed Web interface . ( Question 1 : A = 35 % , B = 28 % , C = 20 % ; Question 2 : A = 5 % , B = 6 % , C = 4 % ; Question 3 : A = 1 % , B = 0 % , C = 0 % ) 95 % confidence intervals were calculated for the precision for each question using a lower boundary of zero . However , the 95 % confidence limits were overlapping , suggesting no statistical difference between the groups . Conclusion Due to the small number of search es for each arm , this pilot study could not demonstrate a statistically significant difference between the search protocol s. However there was a trend towards higher precision that needs to be investigated in a larger study to determine if PICO can improve the relevancy of search results BACKGROUND About a quarter of familial Mediterranean fever ( FMF ) patients are partially or totally resistant to colchicine . A previous observation reported that acute attacks may be shortened by administration of interferon alpha ( IFN ) . OBJECTIVE We design ed a double-blind , placebo-controlled trial to test our initial observations of a beneficial response with IFN in FMF attacks . METHODS We treated 34 acute abdominal attacks with IFN 5 million IU or placebo sc in the early phase of the attack . Leucocytes , thrombocytes , the erythrocyte sedimentation rate , fibrinogen , C-reactive protein ( CRP ) , serum amyloid A protein ( SAA ) , haptoglobin , transferrin , IL-1beta and TNF-alpha were measured at hours 0 , 6 , 12 , 24 and 48 . RESULTS The median time to recovery in those treated with IFN and placebo was not significantly different , while the leucocytosis and high levels of fibrinogen were significantly more prolonged in placebo-treated patients . CRP and SAA were extremely elevated and peaked at 24h , remaining less marked in the IFN-treated patients but the difference was not statistically significant . Observations regarding the other parameters were unremarkable . CONCLUSIONS Although there were some clues indicating a depressed inflammatory response with IFN , we could not demonstrate a definitive effect of this agent in this double-blind trial . The drug may suppress the acute inflammation of FMF only if administered at the earliest phase . CRP and SAA may be more sensitive indicators of an attack than ESR or fibrinogen Familial Mediterranean fever ( FMF ) , the most common monogenic autoinflammatory disease , is characterized by recurrent self-limited attacks of fever and serositis . Between 5 % and 10 % of patients are resistant to or intolerant of colchicine , the current st and ard of care ( 1 ) . Pyrin , the mutated protein in FMF , has an important role in the regulation of interleukin-1 ( IL-1 ) activation . This knowledge has led to the effective use of IL-1 inhibitors in 50 reported patients with colchicine-resistant FMF , including in one controlled study ( 2,3 ) . In the present study we assessed the efficacy and safety of canakinumab , a selective , fully human anti – IL-1 monoclonal antibody with a terminal half-life of 26 days , in the treatment of children with colchicine-resistant FMF . This 6-month , phase II , open-label , single-arm study ( clinical trials.gov identifier NCT01148797 ) was conducted in 7 Caucasian children with FMF ( 5 boys and 2 girls ; median age 9.5 years [ range 6.8–14.9 ] ) at 2 centers in Israel ( Rambam Medical Center and Shaare Zedek Medical Center ) . The study was approved by the ethics committees at both hospitals , and informed consent was obtained from the parents/legal guardians of the participants . Patients were diagnosed according to the Tel-Hashomer criteria ( 4 ) , with 2 exon 10 mutations on the MEFV gene ( M694V/M694V in 5 , M694V/ V726A in 1 , and M694V/M680I in 1 ) . Participants were all colchicine resistant , having had 3 well-documented acute FMF attacks during the 3 months prior to screening despite treatment with colchicine at 1–2 mg/day ( based on age ) for at least 3 months . Following successful screening , participants were enrolled in a 30-day run-in period . Those who experienced 1 investigator-confirmed FMF attack during this time were eligible for treatment . In addition to continuing daily colchicine treatment at the usual dosage , participants received 3 subcutaneous injections ( 4 weeks apart ) of canakinumab 2 mg/kg ( maximum 150 mg ) , with the first injection ( day 1 ) administered during the next attack following the run-in period . The dose was doubled to 4 mg/kg ( maximum 300 mg ) if an attack occurred between the day 1 and day 29 visits . Day 86 was considered the end of the treatment period ( 4 weeks after administration of the last dose of canakinumab ) . Participants were followed up for another 2 visits ( that occurred between day 126 and 160 ) or until an attack occurred ( whichever occurred first ) . Attacks were then treated with acetaminophen and /or nonsteroidal antiinflammatory drugs only . The primary outcome measure was the proportion of participants with 50 % reduction in the frequency of FMF attacks during the treatment period versus the pretreatment period . Secondary outcome measures included acute-phase reactant levels , health-related quality of life ( Child Health Question naire— Parent Form 50 [ CHQ-PF50 ] ) ( 5 ) , physician ’s global assessment of FMF control , time to attack following the last canakinumab injection ( day 57 ) , and safety and tolerability of canakinumab . Six participants met the primary outcome measure with a 50 % reduction ( range 76–100 % ) in the rate of FMF attacks ( Figure 1 ) . The median 28-day time-adjusted attack rate decreased from 2.7 to 0.3 ( 89 % ) . Three participants did not experience any attacks during the treatment phase . The canakinumab dose was doubled for the second and third injections in 2 participants : a responder who experienced 1 additional brief attack after dose escalation and the single nonresponder , who experienced 3 additional attacks ( 4 attacks overall ) . Compared with 34 attacks over 374 patient-days of followup during the pretreatment phase , only 8 attacks in 601 patient-days were reported during the treatment phase . The proportion of days that participants were experiencing an attack decreased from 24.2 % to 3.6 % . Eighteen of 34 attacks ( 53 % ) were rated as severe or very severe during the pretreatment phase , compared with 0 of 8 during the treatment phase . Following the first injection , clinical manifestations resolved the same day in 4 participants and within 24 hours in 3 . Five participants developed an attack after the last canakinumab injection , within a median of 25 days ( range 5–34 ) . Median C-reactive protein levels normalized by day 8 ( from 74 mg/liter at baseline to 2 mg/liter on day 8 and 1.3 mg/liter on day 86 ) , the erythrocyte sedimentation rate by day 29 ( from 83 mm/hour at baseline to 17 mm/hour on days 29 and 86 ) , and serum amyloid A levels by day 57 ( from 500 mg/liter at baseline to 2.5 mg/liter on day 57 and 12.2 mg/liter on day 86 ) . Health-related quality of life also improved , with an increase in CHQ-PF50 summary scores for both the physical domain ( from a median of 21 at baseline to 46 on day 86 [ mean 50 in the healthy population ] ) and the psychosocial domain ( 31 to 40 ) . The physician ’s global assessment of FMF control at baseline was rated as very poor in 3 participants , poor in 3 , and fair in 1 . By day 86 this had improved to very good in 4 participants and good in 3 . Eleven adverse events ( AEs ) were reported in 4 participants ; 2 were infections . All were mild except for 1 moderate streptococcal throat infection . There were no serious AEs , opportunistic infections , malignancies , or deaths . No significant laboratory abnormalities occurred , and formation of neutralizing antibodies to canakinumab was not observed . No participants discontinued the study or missed a treatment dose because of an AE . The major limitation of this study , which was primarily a proof-of-concept study , was the small sample size . Of note , the proportion of complete responders ( with no attacks ) was lower than has been reported in studies of other autoinflammatory conditions treated with canakinumab , such as cryopyrin-associated periodic syndrome ( 6 ) and tumor necrosis factor receptor – associated periodic syndrome ( 7 ) , but higher than has been reported in systemic juvenile idiopathic arthritis ( 8) . This may be due in part to the selection , for the present study , of patients whose FMF was severe and resistant to colchicine treatment . The proportion of complete responders was slightly greater in this study than in a r and omized trial of rilonacept treatment in a similar FMF population ( 3 ) OBJECTIVES Modified adult disease severity scoring systems are being used for childhood FMF . We aim to test the clinical consistency of two common severity scoring systems and to evaluate the correlation of scores with the type of FMF mutations in paediatric FMF patients since certain mutations are prone to severe disease . METHODS Two hundred and fifty-eight children with FMF were cross-sectionally studied . Assessment of the disease severity was performed by using the modified scoring systems of Mor et al. and Pras et al. Genetic analysis was performed using PCR and restriction endonuclease digestion methods for the presence of 15 FMF gene mutations . FMF mutations were grouped into three based on well-known genotypic-phenotypic associations . Correlation between the mutation groups and the severity scoring systems was assessed . The consistency of the severity scoring systems was evaluated . RESULTS The results of two scoring systems were not statistically consistent with each other ( κ = 0.171 ) . This inconsistency persisted even in a more homogeneous subgroup of patients with only homozygote mutations of M694V , M680I and M694I ( κ = 0.125 ) . There was no correlation between the mutation groups and either of the scoring systems ( P = 0.002 , r = 0,196 for scoring systems of Mor et al. ; P = 0.009 , r = 0.162 for Pras et al. ) . CONCLUSIONS The inconsistency of the two scoring systems and lack of correlation between the scoring systems and mutation groups raises concerns about the reliability of these scoring systems in children . There is a need to develop a scoring system in children based on a prospect i ve registry Nine patients with familial Mediterranean fever ( FMF ) were admitted to a controlled , double-blind trial to determine if there are patients with this disease who are able to abort their acute episodes of pain and fever with short courses of colchicine taken at the onset of attacks . Five patients completed their treatment assignments , and colchicine was significantly effective in aborting the attacks of three but was ineffective in two . The remaining four patients could not be assessed because of insufficient numbers of courses . During the 10 months of the trial , 28 courses of colchicine and 31 of placebo were taken during the early stages of FMF attacks . Twenty-one ( 75 % ) colchicine courses were followed by attacks considered to have been aborted , compared to only three ( 10 % ) placebo courses . This trial shows that patients can recognize the prodrome of their FMF attacks and that some patients can consistently abort their attacks with short courses of colchicine taken at the very onset of symptoms Double blind , r and omized , placebo controlled pilot study of ImmunoGuard -- a st and ardized fixed combination of And rographis paniculata Nees . , Eleutherococcus senticosus Maxim . , Schiz and ra chinensis Bail . , and Glycyrrhiza glabra L. special extracts st and ardized for the content of And rographolide ( 4 m Output:	Colchicine is an effective treatment in FMF
MS21373	*TASK* the task is to summarize an input biomedical literature in six sentences *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 new patient-initiated , pharmacy-based postmarketing surveillance system is described . At the time a new prescription for a targeted drug was filled , 2705 out patients ( experimentals ) r and omly assigned to the new system had a printed notice attached to their medication bags : the information requested them to report any " new or unusual symptoms " during the next 2 weeks by a toll-free telephone number to a trained nonprofessional who conducted a st and ardized adverse drug reaction ( ADR ) interview . To help vali date the new system , another sample of 1109 patients ( controls ) did not receive a request for self-monitoring but were interviewed by telephone 2 weeks later . Target drugs were chosen from two classes for which side effect profiles are well identified : oral antibiotics and tricyclic antidepressants . Results show that within both drug classes , all patient-initiated reports closely matched those obtained from controls ; the experimental and control groups also reported predictably high relative frequencies for the most commonly expected ADRs . Additional analyses suggest that a patient-initiated monitoring system could prove to be a promising complement to existing physician-based surveillance systems BACKGROUND Hospitalization and subsequent discharge home often involve discontinuity of care , multiple changes in medication regimens , and inadequate patient education , which can lead to adverse drug events ( ADEs ) and avoidable health care utilization . Our objectives were to identify drug-related problems during and after hospitalization and to determine the effect of patient counseling and follow-up by pharmacists on preventable ADEs . METHODS We conducted a r and omized trial of 178 patients being discharged home from the general medicine service at a large teaching hospital . Patients in the intervention group received pharmacist counseling at discharge and a follow-up telephone call 3 to 5 days later . Interventions focused on clarifying medication regimens ; review ing indications , directions , and potential side effects of medications ; screening for barriers to adherence and early side effects ; and providing patient counseling and /or physician feedback when appropriate . The primary outcome was rate of preventable ADEs . RESULTS Pharmacists observed the following drug-related problems in the intervention group : unexplained discrepancies between patients ' preadmission medication regimens and discharge medication orders in 49 % of patients , unexplained discrepancies between discharge medication lists and postdischarge regimens in 29 % of patients , and medication nonadherence in 23 % . Comparing trial outcomes 30 days after discharge , preventable ADEs were detected in 11 % of patients in the control group and 1 % of patients in the intervention group ( P = .01 ) . No differences were found between groups in total ADEs or total health care utilization . CONCLUSIONS Pharmacist medication review , patient counseling , and telephone follow-up were associated with a lower rate of preventable ADEs 30 days after hospital discharge . Medication discrepancies before and after discharge were common targets of intervention Eighty anxious and eighty depressed patients were assigned r and omly to receiving one of three versions of an information leaflet about their medication , or to receiving no leaflet at all . Mean medication errors were reduced from 15 to 4 % by provision of suitably constructed leaflets . The results show the practical importance of informing patients about their medication and of paying attention to the difficulty level of any leaflets issued The 24.89 % of Mastomys spp of the total rodents caught in this study is an indication that the number ofMastomys spp in this locality is on the increase compared to the report by Agbonlahor1 who stated that Mastomys spp accounts for about 17.5 % rodents in this locality . The fact that 46.76 % of these were positive for LVCFA is an indication that the spread of the virus is on the increase , especially relative to the high number of Mastomys spp circulating in Ekpoma and its environs . This may account for persistent outbreaks of Lassa fever in Ekpoma . It is believed that these rodents may find their way into homes when their natural habitat is disturbed by farmers operating bush clearing and through indiscriminate bush burning – factors which were suggested to have caused the 1989 outbreak in Ekpoma1 . The fact that non-Mastomys spp in the study were negative for LVCFA shows that only M. natalensis is responsible for the transmission of the virus . The findings of a high ( 46.79 % ) circulating antibody to Lassa virus amongst an increasing prevalence ( 24.89 % ) of M. natalensis in Ekpoma and its environs is of great importance . This disease can be prevented by clearing the bushes around the homes and by maintaining good hygiene when h and ling food An interactive computer program ( Personal Education Program [ PEP ] ) design ed for the learning styles and psychomotor skills of older adults was used to teach older adults about potential drug interactions that can result from self-medication with over-the-counter ( OTC ) agents and alcohol . Subjects used the PEP on notebook computers equipped with infrared sensitive touchscreens . Subjects were recruited from senior centers . Those who met age , vision , literacy , independence , and medication use criteria were r and omly assigned to one of three groups : ( 1 ) PEP plus information booklet ; ( 2 ) information booklet only ; or ( 3 ) control . A repeated measures ( three time periods 2 weeks apart ) , three-group design was used . Users of PEP had significantly greater knowledge and self-efficacy scores than both the conventional and control groups at all three time points . The PEP group reported fewer adverse self-medication behaviors over time . Reported self-medication behaviors did not change over time for either the conventional or control groups . Subjects indicated a high degree of satisfaction with the PEP and reported their intent to make specific changes in self-medication behaviors BACKGROUND Patient safety ' best practice s ' that call for patient participation to prevent adverse drug events have not been rigorously evaluated . OBJECTIVE To consider lessons learned from a patient partnership intervention to prevent adverse drug events among medical in- patients . DESIGN Prospect i ve r and omized , controlled pilot trial . SETTING Boston teaching hospital . Patients . Two hundred and nine adult in- patients on a general medicine unit . INTERVENTION Intervention patients ( n = 107 ) received drug safety information and their medication list ; controls ( n = 102 ) received drug safety information only . Measurements . Adverse drug events and close-call drug errors were identified using chart review and incident reports from nurses , pharmacists , and physicians . Patients and clinicians were surveyed about the intervention . RESULTS In 1053 patient-days at risk , 11 patients experienced 12 adverse drug events and 16 patients experienced 18 close calls . There was a non-significant difference between intervention patients and controls in survey responses and in the adverse drug event rate ( 8.4 % versus 2.9 % , P = 0.12 ) and close-call rate ( 7.5 % versus 9.8 % , P = 0.57 ) . Eleven percent of patients were aware of drug-related mistakes during the hospitalization . Among nurse respondents , 29 % indicated that at least one medication error was prevented when a patient or family member identified a problem . CONCLUSION Partnering with in- patients to prevent adverse drug events is a promising strategy but requires further study to document its efficacy OBJECTIVE To determine the effect of an inpatient self-medication program ( SMP ) on the ability to self-medicate , patient medication knowledge , compliance , and patient morale . DESIGN R and omized controlled clinical trial . POPULATION One hundred seven consecutive patients admitted to a geriatric assessment and rehabilitation program were r and omized to either participate in the SMP or to receive st and ard care . INTERVENTION The SMP was a three-stage program in which patients were given increasing responsibility for the administration of their own medications . MEASUREMENTS Ability to self-medicate on discharge from hospital ; medication compliance at 1 month ; patient medication knowledge ; Philadelphia Morale Scale . MAIN RESULTS Participation in the self-medication program did not increase the proportion of patients who were able to self-medicate on discharge from hospital . Compliance was improved by the program . On a proportional basis , the self-medication group made significantly fewer medication errors than the control group at 1-month follow-up ( 0.045 vs 0.086 , P < .001 ) . There were no significant differences in morale or medication knowledge between the SMP and control groups , although both groups made significant gains in knowledge about the names , administration times , and purpose s of their medications from admission to follow-up ( P < .001 ) . CONCLUSIONS A SMP can improve compliance in geriatric patients who are discharged to the community . Participation in a SMP does not improve patients ' morale nor does it improve their medication knowledge more than pharmacy counselling alone . Participation in a SMP is unlikely to increase the probability that patients will be able to self-medicate on discharge . Cognitive factors limit patients ' ability to self-medicate BACKGROUND A systematic study into outpatient medication reconciliation was conducted to determine if a multifaceted intervention influencing providers and patients reduced discrepancies related to inadequate prescription medication reconciliation in an outpatient setting . METHODS A prospect i ve trial was conducted on 104 primary care patients at the Mayo Clinic . Patients in Phase I received st and ard care . Patients in Phase II received the intervention reconciliation process , which consisted of ( 1 ) mailed letters before appointments to remind patients to bring medication bottles or up date d medication lists to their visits , ( 2 ) verification , and ( 3 ) correction of the medication list in the electronic medical record by the patient , and academic detailing and weekly audit and feedback of performance . RESULTS Interventions result ed in a decrease in prescription medication errors from 88.9 % of the visits in Phase 1 to 66 % of the visits in Phase II ( p = .005 ) and from 98.2 % of the visits in Phase I to 84 % of the visits in Phase II ( p = .0134 ) when all medications were considered . The average number of discrepancies per patient decreased by more than 50 % from 5.24 in Phase I to 2.46 in Phase II . The majority of discrepancies were minor . DISCUSSION A multifaceted intervention including various members of the health care provider team ( and the patient ) is crucial to enhancing medication reconciliation OBJECTIVE To determine whether parental errors in dosing liquid medication can be decreased through education . DESIGN R and omized convenience sample stratified to three study groups . SETTING General pediatric clinic , largely indigent and Latino . PATIENTS A total of 45 English-speaking and 45 Spanish-speaking children diagnosed with otitis media and treated with an antibiotic suspension . INTERVENTION Group 1 patients received the prescription and verbal instructions . Group 2 patients received the prescription and a syringe , then the correct dose was demonstrated . Group 3 patients received the prescription , a syringe with a line marked at the correct dose , and a demonstration . After returning from the pharmacy , parents administered the medication under observation . Parents in group 1 used a dispensing device similar to that planned for home use . The other groups used the syringe . After observation but before discharge , everyone received a syringe with a line marked at the correct dose . Patients were seen again at approximately 1 month , and parents demonstrated how much medication they had administered . MAIN OUTCOME MEASURE Percent of parents who administered the correct dose . RESULTS Patients in group 1 received between 32 % and 147 % of the correct dose , with only 11 of 30 ( 37 % ) receiving the correct dose ( + /-0.2 mL ) . In group 2 , 25 of 30 ( 83 % ) parents administered the correct dose , and in group 3 , 30 of 30 ( 100 % ) gave the correct dose . Simultaneous logistic regression indicated that accuracy of dosage differed across instructional groups and language . At follow-up , 23 of 26 parents demonstrated the correct dose . CONCLUSION Education can decrease medication dosing errors made by both Spanish-speaking and English-speaking parents . Effectiveness was also shown at follow-up Objectives : To estimate the extent , nature and consequences of adverse events in a large National Health Service ( NHS ) hospital , and to evaluate the reliability of a two-stage casenote review method in identifying adverse events . Design : A two-stage structured retrospective patient casenote review . Setting : A large NHS hospital in Engl and . Population : A r and om sample of 1006 hospital admissions between January and May 2004 : surgery ( n = 311 ) , general medicine ( n = 251 ) , elderly ( n = 184 ) , orthopaedics ( n = 131 ) , urology ( n = 61 ) and three other specialties ( n = 68 ) . Main outcome measures : Proportion of admissions with adverse events , the proportion of preventable adverse events , and the types and consequences of adverse events . Results : 8.7 % ( n = 87 ) of the 1006 admissions had at least one adverse event ( 95 % CI 7.0 % to 10.4 % ) , of which 31 % ( n = 27 ) were preventable . 15 % of adverse events led to impairment or disability which lasted more than 6 months and another 10 % contributed to patient death . Adverse events led to a mean increased length of stay of 8 days ( 95 % CI 6.5 to 9 ) . The sensitivity of the screening criteria in identifying adverse events was 92 % ( 95 % CI 87 % to 96 % ) and the specificity was 62 % ( 95 % CI 53 Output:	Existing evidence is confined to the promotion of safe self-management of medication , most notably relating to the self-management of oral anticoagulants
MS21374	*TASK* the task is to summarize an input biomedical literature in six sentences *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 We investigated the efficacy and safety of the sodium glucose cotransporter 2 inhibitor , empagliflozin , added to multiple daily injections of insulin ( MDI insulin ) in obese patients with type 2 diabetes mellitus ( T2DM ) . RESEARCH DESIGN AND METHODS Patients inadequately controlled on MDI insulin ± metformin ( mean HbA1c 8.3 % [ 67 mmol/mol ] ; BMI 34.8 kg/m2 ; insulin dose 92 international units/day ) were r and omized and treated with once-daily empagliflozin 10 mg ( n = 186 ) , empagliflozin 25 mg ( n = 189 ) , or placebo ( n = 188 ) for 52 weeks . Insulin dose was to remain stable in weeks 1–18 , adjusted to meet glucose targets in weeks 19–40 , then stable in weeks 41–52 . The primary end point was change from baseline in HbA1c at week 18 . Secondary end points were changes from baseline in insulin dose , weight , and HbA1c at week 52 . RESULTS Adjusted mean ± SE changes from baseline in HbA1c were −0.50 ± 0.05 % ( −5.5 ± 0.5 mmol/mol ) for placebo versus −0.94 ± 0.05 % ( −10.3 ± 0.5 mmol/mol ) and −1.02 ± 0.05 % ( −11.1 ± 0.5 mmol/mol ) for empagliflozin 10 mg and empagliflozin 25 mg , respectively , at week 18 ( both P < 0.001 ) . At week 52 , further reductions with insulin titration result ed in changes from baseline in HbA1c of −0.81 ± 0.08 % ( −8.9 ± 0.9 mmol/mol ) , −1.18 ± 0.08 % ( −12.9 ± 0.9 mmol/mol ) , and −1.27 ± 0.08 % ( −13.9 ± 0.9 mmol/mol ) with placebo , empagliflozin 10 mg , and empagliflozin 25 mg , respectively , and final HbA1c of 7.5 % ( 58 mmol/mol ) , 7.2 % ( 55 mmol/mol ) , and 7.1 % ( 54 mmol/mol ) , respectively . More patients attained HbA1c < 7 % ( < 53 mmol/mol ) with empagliflozin ( 31–42 % ) versus placebo ( 21 % ; both P < 0.01 ) . Empagliflozin 10 mg and empagliflozin 25 mg reduced insulin doses ( −9 to −11 international units/day ) and weight ( −2.4 to −2.5 kg ) versus placebo ( all P < 0.01 ) at week 52 . CONCLUSIONS In obese , difficult-to-treat patients with T2DM inadequately controlled on high MDI insulin doses , empagliflozin improved glycemic control and reduced weight without increasing the risk of hypoglycemia and with lower insulin requirements Aims /hypothesisType 2 diabetes is difficult to manage in patients with a long history of disease requiring insulin therapy . Moreover , addition of most currently available oral antidiabetic agents increases the risk of hypoglycaemia . Vildagliptin is a dipeptidyl peptidase-IV inhibitor , which improves glycaemic control by increasing pancreatic beta cell responsiveness to glucose and suppressing inappropriate glucagon secretion . This study assessed the efficacy and tolerability of vildagliptin added to insulin therapy in patients with type 2 diabetes . Material s and methods This was a multicentre , 24-week , double-blind , r and omised , placebo-controlled , parallel-group study in patients with type 2 diabetes that was inadequately controlled ( HbA1c = 7.5–11 % ) by insulin . Patients received vildagliptin ( n = 144 ; 50 mg twice daily ) or placebo ( n = 152 ) while continuing insulin therapy . Results Baseline HbA1c averaged 8.4 ± 0.1 % in both groups . The adjusted mean change from baseline to endpoint ( AMΔ ) in HbA1c was −0.5 ± 0.1 % and −0.2 ± 0.1 % in patients receiving vildagliptin or placebo , respectively , with a significant between-treatment difference ( p = 0.01 ) . In patients aged ≥65 years , the AMΔ HbA1c was −0.7 ± 0.1 % in the vildagliptin group vs −0.1 ± 0.1 % in the placebo group ( p < 0.001 ) . The incidence of adverse events was similar in the vildagliptin ( 81.3 % ) and placebo ( 82.9 % ) groups . However , hypoglycaemic events were less common ( p < 0.001 ) and less severe ( p < 0.05 ) in patients receiving vildagliptin than in those receiving placebo . Conclusions /interpretationVildagliptin decreases HbA1c in patients whose type 2 diabetes is poorly controlled with high doses of insulin . Addition of vildagliptin to insulin therapy is also associated with reduced confirmed and severe hypoglycaemia . Clinical Trials.gov ID no. : NCT 00099931 Aims To investigate the efficacy and tolerability of empagliflozin added to basal insulin‐treated type 2 diabetes . Methods Patients inadequately controlled [ glycated haemoglobin ( HbA1c ) > 7 to ≤10 % ( > 53 to ≤86 mmol/mol ) ] on basal insulin ( glargine , detemir , NPH ) were r and omized to empagliflozin 10 mg ( n = 169 ) , empagliflozin 25 mg ( n = 155 ) or placebo ( n = 170 ) for 78 weeks . The baseline characteristics were balanced among the groups [ mean HbA1c 8.2 % ( 67 mmol/mol ) , BMI 32.2 kg/m2 ] . The basal insulin dose was to remain constant for 18 weeks , then could be adjusted at investigator 's discretion . The primary endpoint was change from baseline in HbA1c at week 18 . Key secondary endpoints were changes from baseline in HbA1c and insulin dose at week 78 . Results At week 18 , the adjusted mean ± st and ard error changes from baseline in HbA1c were 0.0 ± 0.1 % ( −0.1 ± 0.8 mmol/mol ) for placebo , compared with −0.6 ± 0.1 % ( −6.2 ± 0.8 mmol/mol ) and −0.7 ± 0.1 % ( −7.8 ± 0.8 mmol/mol ) for empagliflozin 10 and 25 mg , respectively ( both p < 0.001 ) . At week 78 , empagliflozin 10 and 25 mg significantly reduced HbA1c , insulin dose and weight vs placebo ( all p < 0.01 ) , and empagliflozin 10 mg significantly reduced systolic blood pressure vs placebo ( p = 0.004 ) . Similar percentages of patients had confirmed hypoglycaemia in all groups ( 35–36 % ) . Events consistent with urinary tract infection were reported in 9 , 15 and 12 % of patients on placebo , empagliflozin 10 and 25 mg , and events consistent with genital infection were reported in 2 , 8 and 5 % , respectively . Conclusions Empagliflozin for 78 weeks added to basal insulin improved glycaemic control and reduced weight with a similar risk of hypoglycaemia to placebo OBJECTIVE To evaluate the efficacy and tolerability of sitagliptin when added to insulin therapy alone or in combination with metformin in patients with type 2 diabetes . METHODS After a 2 week placebo run-in period , eligible patients inadequately controlled on long-acting , intermediate-acting or premixed insulin ( HbA1c > or = 7.5 % and < or = 11 % ) , were r and omised 1:1 to the addition of once-daily sitagliptin 100 mg or matching placebo over a 24-week study period . The study capped the proportion of r and omised patients on insulin plus metformin at 75 % . Further , the study capped the proportion of r and omised patients on premixed insulin at 25 % . The metformin dose and the insulin dose were to remain stable throughout the study . The primary endpoint was HbA1c change from baseline at week 24 . RESULTS Mean baseline characteristics were similar between the sitagliptin ( n = 322 ) and placebo ( n = 319 ) groups , including HbA1c ( 8.7 vs. 8.6 % ) , diabetes duration ( 13 vs. 12 years ) , body mass index ( 31.4 vs. 31.4 kg/m(2 ) ) , and total daily insulin dose ( 51 vs. 52 IU ) , respectively . At 24 weeks , the addition of sitagliptin significantly ( p < 0.001 ) reduced HbA1c by 0.6 % compared with placebo ( 0.0 % ) . A greater proportion of patients achieved an HbA1c level < 7 % while r and omised to sitagliptin as compared with placebo ( 13 vs. 5 % respectively ; p < 0.001 ) . Similar HbA1c reductions were observed in the patient strata defined by insulin type ( long-acting and intermediate-acting insulins or premixed insulins ) and by baseline metformin treatment . The addition of sitagliptin significantly ( p < 0.001 ) reduced fasting plasma glucose by 15.0 mg/dl ( 0.8 mmol/l ) and 2-h postmeal glucose by 36.1 mg/dl ( 2.0 mmol/l ) relative to placebo . A higher incidence of adverse experiences was reported with sitagliptin ( 52 % ) compared with placebo ( 43 % ) , due mainly to the increased incidence of hypoglycaemia ( sitagliptin , 16 % vs. placebo , 8 % ) . The number of hypoglycaemic events meeting the protocol -specified criteria for severity was low with sitagliptin ( n = 2 ) and placebo ( n = 1 ) . No significant change from baseline in body weight was observed in either group . CONCLUSION In this 24-week study , the addition of sitagliptin to ongoing , stable-dose insulin therapy with or without concomitant metformin improved glycaemic control and was generally well tolerated in patients with type 2 diabetes OBJECTIVE To evaluate the efficacy and long-term safety of linagliptin added to basal insulins in type 2 diabetes inadequately controlled on basal insulin with or without oral agents . RESEARCH DESIGN AND METHODS A total of 1,261 patients ( HbA1c ≥7.0 % [ 53 mmol/mol ] to ≤10.0 % [ 86 mmol/mol ] ) on basal insulin alone or combined with metformin and /or pioglitazone were r and omized ( 1:1 ) to double-blind treatment with linagliptin 5 mg once daily or placebo for ≥52 weeks . The basal insulin dose was kept unchanged for 24 weeks but could thereafter be titrated according to fasting plasma glucose levels at the investigators ’ discretion . The primary end point was the mean change in HbA1c from baseline to week 24 . The safety analysis incorporated data up to a maximum of 110 weeks . RESULTS At week 24 , HbA1c changed from a baseline of 8.3 % ( 67 mmol/mol ) by −0.6 % ( −6.6 mmol/mol ) and by 0.1 % ( 1.1 mmol/mol ) with linagliptin and placebo , respectively ( treatment difference −0.65 % [ 95 % CI −0.74 to −0.55 ] [ −7.1 mmol/mol ] ; P < 0.0001 ) . Despite the option to uptitrate basal insulin , it was adjusted only slightly upward ( week 52 , linagliptin 2.6 IU/day , placebo 4.2 IU/day ; P < 0.003 ) , result ing in no further HbA1c improvements . Frequencies of hypoglycemia ( week 24 , linagliptin 22.0 % , placebo 23.2 % ; treatment end , linagliptin 31.4 % , placebo 32.9 % ) and adverse events ( linagliptin 78.4 % , placebo 81.4 % ) were similar between groups . Output:	Without increasing hypoglycaemia , SGLT2 inhibitors showed better glycaemic control and greater weight reduction than DPP4 inhibitors in patients with T2DM inadequately controlled with insulin .
MS21375	*TASK* the task is to summarize an input biomedical literature in six sentences *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 review the literature on strategies to optimize medication adherence in community-dwelling older adults and to make recommendations for clinical practice . METHODS : A systematic literature search was conducted using the MEDLINE , CINAHL , PsycINFO , International Pharmaceutical Abstract s , and EMBASE data bases for r and omized controlled trials examining strategies to optimize medication adherence in patients aged 65 or older prescribed long-term medication regimens . Additional studies were found by examining the reference lists of systematic review s and selected papers . 34 papers reporting on 33 studies met the eligibility criteria and were included in this review . RESULTS : Improvement in adherence was mixed across the studies examining educational interventions , with only 12 of the 28 studies showing improvement in adherence ; most were delivered by pharmacists . Effect sizes for the statistically significant educational interventions ranged from Cohen 's d = 0.14 to 4.93 . Four of the 5 interventions using memory aids and cues , some in conjunction with newer technologies , improved adherence . Effect sizes for the statistically significant interventions using memory aids and cues ranged from Cohen 's d = 0.26 to 2.72 . CONCLUSION : The evidence from this review does not clearly support one single intervention to optimize medication adherence in older patients . Future studies should explore suggestive strategies , such as tailored interventions involving ongoing contact , and should endeavor to correct method ologic weaknesses found in the literature Objective This study examined the psychometric properties of the Korean version of the eight-item Morisky Medication Adherence Scale ( MMAS-8 ) to measure adherence to diabetes medication in patients with type 2 diabetes mellitus . Methods The English version of the MMAS-8 was translated into Korean and administered to patient with type 2 diabetes mellitus via face-to-face interviews , conducted by an independent interviewer . Patient characteristics and glycosylated haemoglobin ( HbA1c ) levels were assessed at the same clinic visit . A proportion of patients was r and omly selected for 2-week test-retest reliability via telephone interviews . Convergent validity of the MMAS-8 against a four-item MMAS , correlations with HbA1c levels and construct validity of the MMAS-8 were evaluated . Results In total , 317 patients were included ; 70 completed the 2-week test – retest interview . Internal consistency reliability was moderate and test – retest reliability of the MMAS-8 was excellent , although a ceiling effect was detected . Good convergent validity was shown by the high correlation of the new scale scores with the original MMAS-4 . A significant association was found between MMAS-8 scores and HbA1c levels . Using glycaemic control as a gold st and ard , sensitivity was 74.1 % and specificity was 38.3 % . Explanatory factor analysis identified three dimensions of the scale . Conclusions In light of acceptable reliability and validity , the MMAS-8 is a simple and quick method for the assessment of medication adherence among patient with type 2 diabetes mellitus , in a busy clinic setting Background The clinical benefits of any new treatment depend substantially on patient acceptance and treatment satisfaction , because only well-accepted treatments will be widely used . Thus , it is important to underst and how patients experience a new treatment . Objective This study assessed the psychometric properties of a question naire ( PRAM-TSQ ) design ed to measure treatment satisfaction in patients using pramlintide ( an analog of amylin , a glucoregulatory hormone co-secreted with insulin ) , which is design ed to improve glucose control . Methods Patients with diabetes completed the 14-item PRAM-TSQ at the end of 2 separate placebo-controlled , double-blind , r and omized clinical trials in which they added active or placebo pramlintide to their established insulin regimen . Factor analysis was used to assess item clustering for the PRAM-TSQ , and the Cronbach 's α measure of inter-item agreement was used to assess scale reliability . PRAM-TSQ validity was assessed by comparing scores between treatment arms , and effect sizes were measured by the η statistic . Validity was also assessed by associations ( Pearson correlations ) between the PRAM-TSQ and clinical study outcomes ( end of study values and during study changes in clinical measures : postpr and ial glucose [ PPG ] , A1C , weight , and insulin requirements ) . Results Scaling revealed 4 PRAM-TSQ components : Global Benefits , Specific Benefits , Absence of Side Effects , Treatment Preference . The total composite PRAM-TSQ had good reliability in both studies ( type 1 α = .93 ; type 2 α = .94 ) ; subscale reliabilities ranged from .65 to 94 . Composite scores differed for pramlintide-treated and placebo-treated patients ( type 1 P < .01 ; type 2 P < .05 ) , and were associated with lower PPG , weight , and insulin requirements ( all P < .05 ) . Results were similar for PRAM-TSQ subscales assessing Global Benefits and Treatment Preference ; Specific Benefits subscale scores were associated with lower PPG and weight ( all P < .05 ) . Conclusions The PRAM-TSQ shows evidence of being a valid , reliable instrument for assessing treatment satisfaction in patients using pramlintide . The subscales are comprehensive and sensitive to the known potential effects of pramlintide treatment . Diabetes educators can use patient responses to the PRAM-TSQ to facilitate treatment adherence by reminding patients of treatment benefits they experience and by helping patients overcome negative effects they report Background We examined the psychometric properties of the Korean version of the 8-item Morisky Medication Adherence Scale ( MMAS-8 ) among adults with hypertension . Methods A total of 373 adults with hypertension were given face-to-face interviews in 2 cardiology clinics at 2 large teaching hospitals in Seoul , South Korea . Blood pressure was measured twice , and medical records were review ed . About one-third of the participants ( n = 109 ) were r and omly selected for a 2-week test-retest evaluation of reliability via telephone interview . Results Internal consistency reliability was moderate ( Cronbach α = 0.56 ) , and test-retest reliability was excellent ( intraclass correlation = 0.91 ; P < 0.001 ) , although a ceiling effect was detected . The correlation of MMAS-8 scores with scores for the original 4-item scale indicated that convergent validity was good ( r = 0.92 ; P < 0.01 ) . A low MMAS-8 score was significantly associated with poor blood pressure control ( χ2 = 29.86 ; P < 0.001 ; adjusted odds ratio = 5.08 ; 95 % CI , 2.56–10.08 ) . Using a cut-off point of 6 , sensitivity and specificity were 64.3 % and 72.9 % , respectively . Exploratory factor analysis identified 3 dimensions of the scale , with poor fit for the 1-dimensional construct using confirmatory factory analysis . Conclusions The MMAS-8 had satisfactory reliability and validity and thus might be suitable for assessment and counseling regarding medication adherence among adults with hypertension in a busy clinical setting in Korea Background : The ASK-20 survey is a previously vali date d patient-report measure of barriers to medication adherence and adherence-related behavior . Objective : To derive and vali date a shorter version of the ASK-20 scale . Methods : Patients with asthma , diabetes , and congestive heart failure were recruited from a university medical center . Participants completed the ASK-20 survey and other question naires . Approximately one-third of participants were r and omized to a 2-week retest administration . Item performance and results of an exploratory factor analysis were examined for item reduction and subscale identification . Subsequent analyses examined reliability and validity of the shorter version of the ASK . Results : A total of 112 patients participated ( 75.9 % female ; mean age 46.7 y ; 53.6 % African American ) . Eight items were dropped from the ASK-20 based on factor loadings , floor effects , Cronbach 's α , and the ability of each item to discriminate between groups of patients differing in self-reported adherence . The new total score ( ASK-12 ) had good internal consistency reliability ( Cronbach 's α 0.75 ) and test-retest reliability ( intraclass correlation 0.79 ) . Convergent validity was demonstrated through correlations with the Morisky Medication Adherence Scale ( r -0.74 ; p < 0.001 ) , condition-specific measures , the SF-12 Mental Component Score ( r –.32 ; p < 0.01 ) , and proportion of days covered by tilled medication prescriptions in the past 6 months as indicated by pharmacy cl aims data ( r -0.20 ; p = 0.059 ) . The ASK-12 total score also discriminated among groups of patients who differed in self-reported adherence indicators , including whether a dose was missed in the past week , the number of days medication was not taken as directed , and treatment satisfaction . Three subscales were identified ( adherence behavior , health beliefs , inconvenience/forgetfulness ) , and results provided initial support for their validity . Conclusions : The ASK-12 demonstrated adequate reliability and validity , and it may be a useful brief measure of adherence behavior and barriers to treatment adherence The Hill-Bone Compliance to High Blood Pressure Therapy Scale assesses patient behaviors for three important behavioral domains of high blood pressure treatment : 1 ) reduced sodium intake ; 2 ) appointment keeping ; and 3 ) medication taking . This scale is comprised of 14 items in three subscales . Each item is a four point Likert type scale . The content validity of the scale was assessed by a relevant literature review and an expert panel , which focused on cultural sensitivity and appropriateness of the instrument for low literacy . Internal consistency reliability and predictive validity of the scale were evaluated using two community based sample s of hypertensive adults enrolled in clinical trials of high blood pressure care and control . The st and ardized alpha for the total scale were 0.74 and 0.84 , and the average interitem correlations of the 14 items were 0.18 and 0.28 , respectively . The construct and predictive validity of the scale was assessed by factor analysis and by testing of theoretically derived hypotheses regarding whether the scale demonstrated consistent and expected relationships with related variables . In this study , high compliance scale scores predicted significantly lower levels of blood pressure and blood pressure control . Moreover , high compliance scale scores at the baseline were significantly associated with blood pressure control at both baseline and at follow up in the two independent sample s. This brief instrument provides a simple method for clinicians in various setting s to use to assess patients ' self reported compliance levels and to plan appropriate interventions Background : Patient self-report is a practical method for measuring adherence , but little is known about its optimal use . Objectives : To examine the retest reliability and predictive validity of 3 different types of self-report adherence measures among patients with common chronic illnesses . Research Design : Correlation and regression analyses of data from an ongoing r and omized controlled trial . Subjects : Patients ( N = 415 ) aged ≥40 years recruited from a primary care network with arthritis , asthma , chronic lung disease , congestive heart failure , depression , and /or diabetes mellitus , plus impairment in ≥1 basic activity and /or a score of ≥4 on the 10-item Center for Epidemiologic Studies Depression Scale . Measures : Self-report adherence ( administered variously at baseline , 2 , 4 , and 6 weeks , and 6 months ) : number of pills taken/number of pills prescribed ( PT/PP ) , using 1–7 days recall , and global reports of medication adherence and overall adherence tendencies . Six-month functional outcomes : Health Assessment Question naire ( HAQ ) and Short Form-36 ( SF-36 ) . Results : Correlation coefficients among contemporaneously administered 1–7 days PT/PP measures were ≥0.78 . Correlations among PT/PP measures and global adherence measures , and among PT/PP measures at 2 and 4 weeks , ranged from 0.11 to 0.54 . PT/PP measures using ≥3–4 days recall significantly predicted adjusted 6-month HAQ but not SF-36 score . Conclusions : Self-report PT/PP and general medication adherence measures tap different behavioral constructs . Self-reported PT/PP at a given point in time is not necessarily representative of medication adherence over time . Among chronically ill patients , 3–4 days recall of PT/PP yield adherence estimates , which are practically as reliable and valid as longer intervals and which predict functional outcomes Output:	The MMAS-8 ( Morisky Medication Adherence Scale–8 items ) and the Hill-Bone scale were the most frequently used instruments . They were found to be well vali date d , with strong evidence for internal consistency and strong positive evidence for reliability , structural validity , hypothesis testing , and criterion validity . Conclusions The MMAS-8 and Hill-Bone scale seem to be well-vali date d instruments for assessing medication adherence in adults at risk for metabolic syndrome .
MS21376	*TASK* the task is to summarize an input biomedical literature in six sentences *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 It is unclear whether cemented or uncemented hemiarthroplasty is the best treatment option in elderly patients with displaced femoral neck fractures . Previous r and omized trials comparing cemented and uncemented hemiarthroplasty have conflicting results . We conducted a r and omized controlled trial to compare cemented and uncemented hemiarthroplasty . Methods This multicenter parallel-r and omized controlled trial included patients of 70 years and older with a displaced femoral neck fracture ( Garden type III or IV ) . Inclusion was between August 2008 and June 2012 . Patients were r and omized between a cemented hemiarthroplasty , type Müller Straight Stem or an uncemented hemiarthroplasty , type DB-10 . Primary outcomes were complications , operation time , functional outcome ( measured by Timed-Up- and -Go ( TUG ) and Groningen Activity Restriction Scale ( GARS ) ) and mid-thigh pain . Health Related Quality of Life ( HRQoL , expressed with the SF-12 ) was measured as an secondary outcome . Follow up was 1 year . Results In total 201 patients were included in the study ( 91 uncemented , 110 cemented hemiarthroplasties ) The uncemented group showed more major local complications ( intra- and postoperative fractures and dislocations ) odds ratio ( 95 % confidence interval ) 3.36 ( 1.40 to 8.11 ) . There was no difference in mean operation time ( 57.3 vs 55.4 min ) . There were no differences in functional outcomes ( TUG 12.8 ( 9.4 ) vs. 13.9 ( 9.0 ) , GARS 43.2 ( 19.7 ) vs. 39.2 ( 16.5 ) ) and mid-thigh pain ( 18.6 vs 21.6 % ) . Physical component SF-12 HRQoLwas lower in the uncemented group ( 30.3 vs. 35.3 p < 0.05 after six weeks , 33.8 vs 38.5 p < 0.05 after 12 weeks ) . Conclusion A cemented hemiarthroplasty in elderly patients with a displaced femoral neck fracture results in less complications compared to an uncemented hemiarthroplasty . Trial registration Netherl and s Trial Registry ; NTR 1508 , accepted date 27 okt Objective : To prospect ively compare the functional outcome associated with cemented and uncemented hemiarthroplasty . Design : Prospect i ve r and omized control trial . Setting : University-affiliated level 1 trauma center . Patients / Participants : All individuals design ated for hemiarthroplasty , older than 55 years , with a nonpathologic displaced femoral neck fracture and the ability to ambulate 10 feet independently before injury [ 269 patients ( 274 hips ) presented with displaced femoral neck fracture , 130 patients ( 48.3 % ) enrolled , and 5 patients ( 3.8 % ) withdrew ] . Intervention : Hip hemiarthroplasty with a cemented femoral prosthesis ( VerSys LD/Fx ; Zimmer , Warsaw , IN ) or an uncemented component ( VerSys Beaded FullCoat ; Zimmer , Warsaw , IN ) . Main Outcome Measures : Instrumental Activities of Daily Living and Physical Activities of Daily Living scales ( Older Americans Re sources and Services Instrument ) and the Energy/Fatigue Scale . Results : No statistically significant differences were present in the groups ' preoperative or intraoperative characteristics , including American Society of Anesthesiologists grade , operative time , anesthesia time , use of perioperative & bgr;-blockers , estimated blood loss , or the rate of intraoperative fracture . Postoperatively , no difference was found in hemoglobin level , transfusion rate , discharge disposition , or acute complication rate . At 30-day , 60-day , and 1-year follow-ups , no clinical ly or statistically significant differences were found in mortality , disposition , need for assistance with ambulation , Older Americans Re sources and Services Activities of Daily Living subscales , or the Energy/Fatigue Scale . Conclusions : In the treatment of nonpathologic displaced femoral neck fractures , the use of cemented and uncemented femoral components is associated with similar functional outcome at 1 year . Practitioners may inform their clinical decisions using these equally good results . Level of Evidence : Therapeutic Level II . See page 128 for a complete description of levels of evidence Background Displaced femoral neck fractures usually are treated with hemiarthroplasty . However , the degree to which the design of the implant used ( cemented or uncemented ) affects the outcome is not known and may be therapeutically important . Questions / purpose sIn this r and omized controlled trial , we sought to compare cemented with cementless fixation in bipolar hemiarthroplasties at 5 years in terms of ( 1 ) Harris hip scores ; ( 2 ) femoral fractures ; ( 3 ) overall health outcomes using the Barthel Index and EQ-5D scores ; and ( 4 ) complications , reoperations , and mortality since our earlier report on this cohort at 1-year followup . Methods We present followup at a median of 5 years after surgery ( range , 56–65 months ) from a r and omized trial comparing a cemented hemiarthroplasty ( 112 hips ) with an uncemented , hydroxyapatite-coated hemiarthroplasty ( 108 hips ) , both with a bipolar head . Results were previously reported at 1-year followup . Harris hip scores , Barthel Index , and EQ-5D scores were assessed by one research nurse and one orthopaedic surgeon . Complications and reoperations were determined by chart review and radiographs examined by three orthopaedic surgeons . Sixty patients ( 56 % ) had died in the cemented group and 63 ( 60 % ) in the uncemented group . Respectively , three and two patients ( 2.7 % and 1.9 % ) were completely lost to followup . Results Harris hip scores at 5 years were higher in the uncemented group than in the cemented group ( 86.2 versus 76.3 ; mean difference 9.9 ; 95 % confidence interval [ CI ] , 1.9–17.9 ) . The prevalence of postoperative periprosthetic femoral fractures was 7.4 % in the uncemented group and 0.9 % in the cemented group ( hazard ratio [ HR ] , 9.3 ; 95 % CI , 1.16–74.5 ) . Barthel Index and EQ-5D scores were not different between the groups . Between 1 and 5 years , we found no additional infections or dislocations . The mortality rate was not different between the groups ( HR , 1.2 ; 95 % CI , 0.82–1.7 ) . Conclusions Both arthroplasties may be used with good medium-term results after displaced femoral neck fractures . The uncemented hemiarthroplasty may result in higher hip scores but appears to carry an unacceptably high risk of later femoral fractures . Level of Evidence Level I , therapeutic study . See the Guidelines for Authors for a complete description of levels of evidence Objective To compare the functional results after displaced fractures of the femoral neck treated with internal fixation or hemiarthroplasty . Design R and omised trial with blinding of assessment s of functional results . Setting University hospital . Participants 222 patients ; 165 ( 74 % ) women , mean age 83 years . Inclusion criteria were age above 60 , ability to walk before the fracture , and no major hip pathology , regardless of cognitive function . Interventions Closed reduction and two parallel screws ( 112 patients ) and bipolar cemented hemiarthroplasty ( 110 patients ) . Follow-up at 4 , 12 , and 24 months . Main outcome measures Hip function ( Harris hip score ) , health related quality of life ( Eq-5d ) , activities of daily living ( Barthel index ) . In all cases high scores indicate better function . Results Mean Harris hip score in the hemiarthroplasty group was 8.2 points higher ( 95 % confidence interval 2.8 to 13.5 points , P=0.003 ) at four months and 6.7 points ( 1.5 to 11.9 points , P=0.01 ) higher at 12 months . Mean Eq-5d index score at 24 months was 0.13 higher in the hemiarthroplasty group ( 0.01 to 0.25 , P=0.03 ) . The Eq-5d visual analogue scale was 8.7 points higher in the hemiarthroplasty group after 4 months ( 1.9 to 15.6 , P=0.01 ) . After 12 and 24 months the percentage scoring 95 or 100 on the Barthel index was higher in the hemiarthroplasty group ( relative risk 0.67 , 0.47 to 0.95 , P=0.02 . and 0.63 , 0.42 to 0.94 , P=0.02 , respectively ) . Complications occurred in 56 ( 50 % ) patients in the internal fixation group and 16 ( 15 % ) in the hemiarthroplasty group ( 3.44 , 2.11 to 5.60 , P<0.001 ) . In each group 39 patients ( 35 % ) died within 24 months ( 0.98 , 0.69 to 1.40 , P=0.92 ) Conclusions Hemiarthroplasty is associated with better functional outcome than internal fixation in treatment of displaced fractures of the femoral neck in elderly patients . Trial registration NCT00464230 BACKGROUND Controversy exists regarding the use of cement for hemiarthroplasty to treat a displaced subcapital femoral neck fracture in elderly patients . The primary hypothesis of this study was that use of cement would provide better visual analog pain scores following this procedure in an elderly patient population . METHODS Elderly patients ( at least seventy years of age ) without severe cardiopulmonary compromise who presented to one institution with a displaced subcapital femoral neck fracture were offered inclusion in the study . One hundred and sixty patients ( mean age , eighty-five years ) with an acute displaced femoral neck fracture were r and omly allocated to hemiarthroplasty with either a cemented Exeter or an uncemented Zweymüller Alloclassic component . Clinical and radiographic follow-up was performed for two years and the outcomes were recorded by a blinded assessor . The main clinical outcome measures were pain , mortality , mobility , complications , reoperations , and quality of life measured with use of vali date d instruments . RESULTS The mean visual analog pain score at rest did not differ significantly between the groups . The total number of complications was greater in the uncemented group ( sixty-three compared with twenty-eight in the cemented group ) . Subsidence was significantly more common in the uncemented group ( eighteen compared with one in the cemented group ) . Intraoperative or postoperative fracture was also significantly more common in the uncemented group ( eighteen compared with one in the cemented group ) . The mortality rate did not differ significantly between the groups at any time point ( thirty-five deaths in the uncemented group compared with thirty-two in the cemented group at two years ) . The Oxford hip score was significantly poorer in the uncemented group at six weeks ( 38.8 compared with 35.7 in the cemented group ) , and it was also poorer or similar at later follow-up time points although the differences were not significant . There was also a trend toward poorer mobility and greater dependence on walking aids in the cemented group . The postoperative Short Musculoskeletal Function Assessment and Mini-Mental State Examination scores did not differ significantly between the groups . CONCLUSIONS In elderly patients ( seventy years or older ) without severe cardiopulmonary compromise who were treated with hemiarthroplasty for a displaced femoral neck fracture , use of a cemented Exeter implant and use of an uncemented Alloclassic implant provided a comparable outcome with regard to pain . However , implant-related complication rates were significantly lower in the group treated with a cemented implant . Trends toward better function and better mobility in the cemented group were observed . These trends reached significance in particular functional scores at some postoperative time points . LEVEL OF EVIDENCE Therapeutic Level II . See Instructions for Authors for a complete description of levels of evidence In a prospect i ve , controlled study , we measured the effect on cardiac output of the introduction of methylmethacrylate during hemiarthroplasty for displaced fractures of the femoral neck . We treated 20 elderly patients who were similar in age , height , weight and preoperative left ventricular function with either cemented or uncemented hemiarthroplasty . Using a transoesophageal Doppler probe , we measured cardiac output before incision and at six stages of the procedure : during the surgical approach , reaming and lavage of the femoral canal , the introduction of cement , the insertion of the prosthesis , and in reduction and closure . We found that before the cement was introduced , there was no difference in stroke volume or cardiac output ( p > 0.25 ) . Cementation produced a transient but significant reduction in cardiac output of 33 % ( p < 0.01 ) and a reduction in stroke volume of 44 % ( p < 0.02 ) . The introduction of cement did not affect the heart Output:	Prosthesis-related complications like fractures and subsidence and general complications like lung complications were more in uncemented group . Mortality at 1 year was more in cemented group . Secondary outcomes Mean surgical time was lesser in uncemented cases . There was no difference in blood loss and re-operation rates . Conclusion Cementing techniques are here to stay , until a better , durable and more stable uncemented stem evolves , that could lessen the complications related to uncemented surgeries and match the cemented implants in pain relief and ambulation
MS21377	*TASK* the task is to summarize an input biomedical literature in six sentences *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 prospect ively study the effects of an incentivized exercise program on physical activity ( PA ) , quality of life ( QOL ) , and burnout among residents and fellows ( RFs ) in a large academic medical center . PARTICIPANTS AND METHODS In January 2011 , all RFs at Mayo Clinic in Rochester , Minnesota ( N=1060 ) , were invited to participate in an elective , team-based , 12-week , incentivized exercise program . Both participants and non participants had access to the same institutional exercise facilities . Regardless of participation , all RFs were invited to complete baseline and follow-up ( 3-month ) assessment s of PA , QOL , and burnout . RESULTS Of the 628 RFs who completed the baseline survey ( 59 % ) , only 194 ( 31 % ) met the US Department of Health and Human Services recommendations for PA . Median reported QOL was 70 on a scale of 1 to 100 , and 182 ( 29 % ) reported at least weekly burnout symptoms . A total of 245 individuals ( 23 % ) enrolled in the exercise program . No significant differences were found between program participants and non participants with regard to baseline demographic characteristics , medical training level , PA , QOL , or burnout . At study completion , program participants were more likely than non participants to meet the Department of Health and Human Services recommendations for exercise ( 48 % vs 23 % ; P<.001 ) . Quality of life was higher in program participants than in non participants ( median , 75 vs 68 ; P<.001 ) . Burnout was lower in participants than in non participants , although the difference was not statistically significant ( 24 % vs 29 % ; P=.17 ) . CONCLUSION A team-based , incentivized exercise program engaged 23 % of RFs at our institution . After the program , participants had higher PA and QOL than non participants who had equal exercise facility access . Residents and fellows may be much more sedentary than previously reported BACKGROUND Informed consent is required for both st and ard cancer treatments and experimental cancer treatments in a clinical trial . Effective and sensitive physician-patient communication about informed consent is difficult to achieve . Our aim was to train doctors in clear , collaborative and ethical communication about informed consent and evaluate the impact of training on doctor behaviour , stress and satisfaction . PARTICIPANTS AND METHODS Participants were 21 oncologists from 10 Australian/New Zeal and ( ANZ ) centres and 41 oncologists from 10 Swiss/German/Austrian ( SGA ) centres . Oncologists were r and omized to participate in a 1-day workshop or not . Patients were recruited before and after the training . Doctors were asked to su bmi t 1 - 2 audiotaped consultations before and after training . Doctors completed outcome measures before and after completing the post-training cohort recruitment . RESULTS Ninety-five consultation interactions were audiotaped . Doctors strongly endorsed the training . ANZ intervention doctors demonstrated a significant increase in collaborative communication ( P = 0.03 ) . There was no effect of training on other doctor behaviours . Trained doctors did not demonstrate reduced stress and burnout . Patient outcomes are presented elsewhere . CONCLUSIONS Training can improve some aspects of the process of obtaining informed consent . Methods to increase the impact of training are required and may include longer training and more intensive follow-up OBJECTIVES To estimate burnout prevalence among pediatric residents and to evaluate the impact of a brief intervention aim ed at controlling burnout . METHODS A r and omized controlled trial was conducted on 74 pediatric residents . The Maslach Burnout Inventory was administered to all subjects , and demographic information was gathered ( age , gender , children , cohabitants , and residency year ) . The experimental group ( n = 37 ) participated in self-care workshops over the course of 2 months , and the control group ( n = 37 ) did not receive any intervention . After the intervention , the Maslach Burnout Inventory was administered again to all participants . All potential predictors of burnout were included in a logistic regression model . The efficacy of the intervention was evaluated by the chi-square test . P values < 0.05 were considered significant . RESULTS The burnout prevalence among pediatric residents was 66 % . After controlling for age , gender , children , and cohabitants , the prevalence of burnout was significantly higher among third-year residents ( odds ratio = 11.8 ; 95 % confidence interval 2.3 - 59.3 ; p = 0.003 ) . There were no significant differences regarding burnout prevalence in the experimental group between the baseline and post-intervention periods ( p = 0.8 ) or between the two groups after intervention ( p = 0.8 ) . The only difference observed was an improvement regarding " depersonalization " in the experimental group ( p = 0.031 ) . CONCLUSIONS The burnout prevalence among pediatric residents was 66 % and was higher among third-year residents . A brief intervention was not effective in reducing burnout prevalence , despite the achievement of an improvement in " depersonalization . CONTEXT Data are sparse on the effect of varying the duration s of internal medicine attending physician ward rotations . OBJECTIVE To compare the effects of 2- vs 4-week inpatient attending physician rotations on unplanned patient revisits , attending evaluations by trainees , and attending propensity for burnout . DESIGN , SETTING , AND PARTICIPANTS Cluster r and omized crossover noninferiority trial , with attending physicians as the unit of crossover r and omization and 4-week rotations as the active control , conducted in a US university-affiliated teaching hospital in academic year 2009 . Participants were 62 attending physicians who staffed at least 6 weeks of inpatient service , the 8892 unique patients whom they discharged , and the 147 house staff and 229 medical students who evaluated their performance . INTERVENTION Assignment to r and om sequences of 2- and 4-week rotations . MAIN OUTCOME MEASURES Primary outcome was 30-day unplanned revisits ( visits to the hospital 's emergency department or urgent ambulatory clinic , unplanned readmissions , and direct transfers from neighboring hospitals ) for patients discharged from 2- vs 4-week within-attending-physician rotations . Noninferiority margin was a 2 % increase ( odds ratio [ OR ] of 1.13 ) in 30-day unplanned patient revisits . Secondary outcomes were length of stay ; trainee evaluations of attending physicians ; and attending physician reports of burnout , stress , and workplace control . RESULTS Among the 8892 patients , there were 2437 unplanned revisits . The percentage of 30-day unplanned revisits for patients of attending physicians on 2-week rotations was 21.2 % compared with 21.5 % for 4-week rotations ( mean difference , -0.3 % ; 95 % CI , -1.8 % to + 1.2 % ) . The adjusted OR of a patient having a 30-day unplanned revisit after 2- vs 4-week rotations was 0.97 ( 1-sided 97.5 % upper confidence limit , 1.07 ; noninferiority P = .007 ) . Average length of stay was not significantly different ( geometric means for 2- vs 4-week rotations were 67.2 vs 67.5 hours ; difference , -0.9 % ; 95 % CI , -4.7 % to + 2.9 % ) . Attending physicians were more likely to score lower in their ability to evaluate trainees after 2- vs 4-week rotations by both house staff ( 41 % vs 28 % rated less than perfect ; adjusted OR , 2.10 ; 95 % CI , 1.50 - 3.02 ) and medical students ( 82 % vs 69 % rated less than perfect ; adjusted OR , 1.41 ; 95 % CI , 1.06 - 2.10 ) . They were less likely to report higher scores of both burnout severity ( 16 % vs 35 % ; adjusted OR , 0.39 ; 95 % CI , 0.26 - 0.58 ) and emotional exhaustion ( 19 % vs 37 % ; adjusted OR , 0.45 ; 95 % CI , 0.31 to 0.64 ) after 2- vs 4-week rotations . CONCLUSIONS The use of 2-week inpatient attending physician rotations compared with 4-week rotations did not result in an increase in unplanned patient revisits . It was associated with better self-rated measures of attending physician burnout and emotional exhaustion but worse evaluations by trainees . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00930111 Background : Shorter resident duty periods are increasingly m and ated to improve patient safety and physician well-being . However , increases in continuity-related errors may counteract the purported benefits of reducing fatigue . We evaluated the effects of 3 resident schedules in the intensive care unit ( ICU ) on patient safety , resident well-being and continuity of care . Methods : Residents in 2 university-affiliated ICUs were r and omly assigned ( in 2-month rotation-blocks from January to June 2009 ) to in-house overnight schedules of 24 , 16 or 12 hours . The primary patient outcome was adverse events . The primary resident outcome was sleepiness , measured by the 7-point Stanford Sleepiness Scale . Secondary outcomes were patient deaths , preventable adverse events , and residents ’ physical symptoms and burnout . Continuity of care and perceptions of ICU staff were also assessed . Results : We evaluated 47 ( 96 % ) of 49 residents , all 971 admissions , 5894 patient-days and 452 staff surveys . We found no effect of schedule ( 24- , 16- or 12-h shifts ) on adverse events ( 81.3 , 76.3 and 78.2 events per 1000 patient-days , respectively ; p = 0.7 ) or on residents ’ sleepiness in the daytime ( mean rating 2.33 , 2.61 and 2.30 , respectively ; p = 0.3 ) or at night ( mean rating 3.06 , 2.73 and 2.42 , respectively ; p = 0.2 ) . Seven of 8 preventable adverse events occurred with the 12-hour schedule ( p = 0.1 ) . Mortality rates were similar for the 3 schedules . Residents ’ somatic symptoms were more severe and more frequent with the 24-hour schedule ( p = 0.04 ) ; however , burnout was similar across the groups . ICU staff rated residents ’ knowledge and decision-making worst with the 16-hour schedule . Interpretation : Our findings do not support the purported advantages of shorter duty schedules . They also highlight the trade-offs between residents ’ symptoms and multiple secondary measures of patient safety . Further delineation of this emerging signal is required before widespread system change . Trial registration : Clinical Trials.gov , no. NCT00679809 RATIONALE Around-the-clock intensivist presence in intensive care units ( ICUs ) has been promoted as necessary to optimize outcomes . Little data have addressed how it affects the multiple stakeholders in such care . OBJECTIVES To assess effects of around-the-clock intensivist presence on intensivists , patients , families , housestaff , and nurses . METHODS This 32-week , crossover pilot trial of two intensivist staffing models , performed in two Canadian ICUs , alternated 8-week blocks of two staffing models : the st and ard model , where one intensivist worked for 7 days , taking night call from home ; and the shift work model , where one intensivist worked 7 day shifts , while other intensivists remained in the ICU at night . MEASUREMENTS AND MAIN RESULTS Surveys scaled from 0 - 100 points assessed outcomes for 24 intensivists ( primary outcome : burnout ) ; 119 families ( satisfaction ) ; 74 nurses ( satisfaction with collaboration and communications , role conflict ) ; and 34 housestaff ( autonomy , supervision , and learning opportunities ) . Outcomes for 501 patients included mortality , length of stay , and re source use . Intensivists doing shift work experienced less burnout ( -6.9 points ; P = 0.04 ) . Adjusted hospital mortality ( odds ratio , 1.22 ; P = 0.44 ) , ICU length of stay ( -6 h ; P = 0.46 ) , and family satisfaction ( 0.9 points ; P = 0.79 ) did not differ between staffing models . Under shift work staffing , nurses reported more role conflict ( 9 points ; P < 0.001 ) , whereas nighttime housestaff reported less autonomy , more supervision , but no difference in learning opportunities . CONCLUSIONS Shiftwork staffing was better for intensivists and most were receptive once they had experienced it . Although there were no evident negative outcomes for patients or families , further evaluation is needed to clarify how around-the-clock intensivist staffing influences the various stakeholders in ICU care , given power considerations in this study . Clinical trial registered with www . clinical trials.gov ( NCT 01146691 ) Background Internship and residency are difficult times with novice practitioners facing new challenges and stressors . Junior doctors may experience burnout , a syndrome that encompasses three dimensions : emotional exhaustion , depersonalisation and reduced personal accomplishment . While there is some existing literature on the prevalence of burnout in junior doctors , there are few studies on interventional strategies . Output:	This systematic review and meta- analysis showed that ( 1 ) organization-directed interventions were associated with moderate reduction in burnout score , ( 2 ) physician-directed interventions were associated with small reduction in burnout score , ( 3 ) organization-directed interventions reduced more the depersonalization than physician-directed interventions , ( 4 ) organization-directed interventions were related to a more improvement of the personal accomplishment than physician-directed interventions . This meta analysis found that physicians could gain important benefits from interventions to reduce burnout , especially from organizational strategies , by viewing burnout rooted in issues related to the working environment and organizational culture
MS21378	*TASK* the task is to summarize an input biomedical literature in six sentences *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 effects of growth hormone ( GH ) on the luminal transport of amino acids and glucose by the human small intestine were investigated . Summary Background Data The anabolic effect of growth hormone administration is associated with nitrogen retention and an increase muscle strength , but the impact of growth hormone on nutrient uptake from the gut lumen has not been examined . Methods Twelve healthy patients received a daily subcutaneous dose of low-dose GH ( 0.1 mg/kg ) , high-dose GH ( 0.2 mg/kg ) , or no treatment ( controls ) for 3 days before surgery . At operation , ileum ( 8 patients ) or jejunum ( 4 patients ) was resected , and brush border membrane vesicles ( BBMVs ) were prepared by differential centrifugation . Vesicle purity was confirmed by a 16-fold enrichment of marker enzymes . The carrier-mediated transport of glutamine ( System B ) , leucine ( System L ) , alanine ( System B ) , arginine ( System y+ ) , MeAIB ( methyl α-aminoisobutyric acid [ System A ] ) , and glucose ( Na+-dependent glucose transporter ) by BBMVs was measured by a rapid mixing/filtration technique . Results Treatment with low-dose GH result ed in a statistically insignificant increase in amino acid transport rates in jejunal and ileal BBMVs . High-dose GH result ed in a generalized 20%- to 70%- stimulation of amino acid transport , whereas glucose transport was not affected . The effects of GH were similar in ileum and jejunum . Kinetic analysis of the transport of glutamine ( the most abundant amino acid in the body and the principal gut fuel ) and the essential amino acid leucine revealed that the increase in transport was caused by a 50 % increase in carrier Vmax , consistent with an increase in the number of functional carriers in the brush border membrane . Pooled analysis of transport velocities demonstrated that total rates of amino acid uptake from the gut lumen were increased significantly by 35 % in GH-treated patients . Conclusions The ability of GH to enhance amino acid uptake from the gut lumen provides energy and precursors for protein synthesis in the gut mucosa , as well as additional substrate for anabolism in other organs This study was design ed to determine whether alanyl glutamine-containing total parental nutrition ( TPN ) can restore the impaired adaptive process of the remaining intestine , observed with administration of conventional TPN , after massive small-bowel resection . Seventy-four male Sprague-Dawley rats weighing 250 g were r and omly divided into seven groups . Group I rats ( n = 10 ) were killed after overnight fasting . Group II animals ( n = 32 ) underwent massive small bowel resection ( 85 % ) with preservation of the first 15 cm of jejunum . Group III animals ( n = 32 ) were also su bmi tted to massive small-bowel resection with preservation of 15 cm of terminal ileum . Three different TPN solutions were prepared . Solution A was a conventional formulation that did not contain glutamine . Solution B contained 1.88 times the amino acid concentration of solution A. Solution C was prepared by adding alanyl glutamine ( 2 g/100 mL ) to solution A. Solutions B and C were isonitrogenous and isocaloric . Each solution was infused to groups II and III , which were subdivided into groups IIA ( n = 10 ) , IIB ( n = 11 ) , IIC ( n = 11 ) , IIIA ( n = 10 ) , IIIB ( n = 11 ) , and IIIC ( n = 11 ) . After 1 week of TPN ( 270 kcal/kg per day ) , the experimental animals were killed and the intestine was taken for examination . Final body weight did not differ significantly among the groups , and there was no difference in nitrogen balance among the animals that received solution B or C. ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND & AIMS The effects of parenteral growth hormone , glutamine supplementation , and a high carbohydrate-low fat ( HCLF ) diet on gut adaptation in short-bowel syndrome are unclear . The aim of this study was to compare effects of this treatment regimen and placebo in patients with short-bowel syndrome . METHODS A r and omized , 6-week , double-blind , placebo-controlled , crossover study in 8 patients with short-bowel syndrome ( average small bowel length , 71 cm ; mean duration , 12.9 years ) was performed . Active treatment was growth hormone ( 0.14 mg.kg-1.day-1 ) , oral glutamine ( 0.63 g.kg-1.day-1 ) , and the HCLF diet for 21 days . The weight , basal metabolic rate , nutrient and electrolyte balance , serum insulin-like growth factor I levels , D-xylose absorption , morphology and DNA proliferation of small intestinal mucosa , and gastrointestinal transit were evaluated . Treatments were compared by paired t test . RESULTS Active treatment transiently increased body weight , significantly but modestly increased the absorption of sodium and potassium , and decreased gastric emptying . The assimilation of macronutrients , stool volumes , and morphometry of small bowel mucosa were not statistically different in the two treatment arms . CONCLUSIONS Although treatment with growth hormone , glutamine , and HCLF diet for 3 weeks result ed in modest improvements in electrolyte absorption and delayed gastric emptying , there were no improvements in small bowel morphology , stool losses , or macronutrient absorption BACKGROUND A previous controlled study of ten patients with short bowel syndrome ( SBS ) reported human recombinant growth hormone result ed in a significant increase in body weight and lean body mass ( LBM ) without clinical edema . The aim of this study was to assess the effect of growth hormone , glutamine , and diet on body composition . METHODS A r and omized , 6-week , double-blind , placebo-controlled , crossover study was performed in eight patients . Active treatment was 21 days of growth hormone , oral glutamine , and a high-carbohydrate-low-fat ( HCLF ) diet . Body composition was determined by dual-energy x-ray absorptiometry ( DEXA ) scan . Treatments were compared by paired t test . RESULTS Active treatment result ed in significant increases in body weight ( mean 3.02 + /- 0.7 kg , p < .05 ) and lean body mass , ( mean 3.96 + /- 0.5 kg , p < .001 ) . Percent body fat was significantly reduced in the actively treated group ( mean -2.51 % + /- 0.4 , p < .001 ) . Body weight returned to base-line within 2 weeks of discontinuing active treatment . Macronutrient and fluid absorption did not increase with active treatment . CONCLUSIONS Treatment with growth hormone , glutamine , and HCLF diet result ed in decreased percent body fat and increased body weight and LBM in patients with SBS , without an increase in macronutrient or fluid absorption . The positive findings are most likely a reflection of increased extracellular fluid because all eight patients developed peripheral edema on active treatment . Furthermore , the positive effect of active treatment does not appear to be sustained once discontinued BACKGROUND Positive effects of high dose growth hormone and glutamine ( GH + GLN ) on body composition in short bowel patients have been described . Lack of effects on intestinal absorption found in some studies has been ascribed to concomitant essential fatty acid ( EFA ) deficiency . This study describes changes in body weight ( BW ) and composition , 24-h urine creatinine excretion , intestinal fatty acid absorption ( total , saturated , unsaturated and EFA ) , and EFA status in relation to treatment with GH + GLN in 8 short bowel patients . METHODS A double-blind , crossover study between placebo and growth hormone ( mean , 0.12 mg/kg/day ) plus oral ( mean , 28 g/day ) and parenteral glutamine ( mean , 5.2 g/day ) for 28 days . Body composition was measured by dual-energy absorptiometry ( DEXA ) scans . Intestinal fatty acid absorption was evaluated in balance studies , and EFAs were measured in plasma phospholipids by gas liquid chromatography . RESULTS Active treatment did not increase BW , lean body mass ( LBM ) , fat mass ( FM ) and bone mass significantly compared with placebo treatment , but BW increased 1.03 kg ( 1.7 % , P < 0.05 ) , LBM 2.93 kg ( 8.7 % , P < 0.001 ) and FM decreased 2.41 kg ( 10.6 % , P < 0.001 ) in comparison with baseline . Twenty-four-hour urine creatinine excretion did not differ between study periods . No changes in intestinal absorption of fatty acids were seen , and no changes in EFAs measured in plasma phospholipids were observed . Only 1 of 8 patients , who did not receive parenteral lipids , had a Holman index above 0.2 , indicative of EFA deficiency . All developed peripheral oedema . CONCLUSIONS Combined high dose growth hormone and glutamine administered for 4 weeks , did not improve absorption of fatty acids or EFA status in short bowel patients . No changes in BW or composition were seen when comparing treatment to placebo periods . The increase in LBM measured by DEXA scan , comparing treatment and baseline periods , was not accompanied by an increase in the 24-h urinary creatinine excretion and is suspected to be associated with an accumulation in extracellular fluids BACKGROUND Massive loss of intestinal surface area results in the short bowel syndrome characterized by malabsorption of fluid , electrolytes , and other nutrients . Although the remaining bowel undergoes morphological and functional adaptation , often these changes are inadequate to support the individual by enteral feedings , and parenteral nutrition is required to prevent dehydration , electrolyte disturbances , and malnutrition . Substances such as growth hormone , glutamine , and fiber exert bowel-specific trophic effects and either directly or indirectly influence nutrient absorption . This study was undertaken to determine whether the co-administration of exogenous growth hormone , supplemental glutamine , and a modified fiber-containing diet could enhance nutrient absorption in patients who had undergone massive intestinal resection . METHODS Ten patients ( 5 men , 5 women , aged 43 + /- 4 years ) with short bowel syndrome were studied 6 + /- 1 years after surgical resection . All patients were admitted to the Clinical Research Center for a 28-day period ; the first week served as a control period when nutritional ( enteral and parenteral ) and medical management simulated usual home therapy . Thereafter , eight patients received exogenous growth hormone , supplemental glutamine , and a modified high-carbohydrate , high-fiber diet . Two patients were treated with the modified diet alone . The efficiency of net nutrient absorption ( percent absorbed ) for total calories , protein , fat , carbohydrate , water , and sodium was calculated from the measured nutrient intake and stool losses . RESULTS Three weeks of treatment with growth hormone , glutamine , and a modified diet increased total caloric absorption from 60.1 + /- 6.0 % to 74.3 + /- 5.0 % ( p < or = .003 ) , protein absorption from 48.8 + /- 4.8 % to 63.0 + /- 5.4 % ( p < or = .006 ) , and carbohydrate absorption from 60.0 + /- 9.8 % to 81.5 + /- 5.3 % ( p < or = .02 ) . Fat absorption did not change ( 61.0 + /- 5.3 % to 60.3 + /- 7.9 % , p = NS ) . Water and sodium absorption increased from 45.7 + /- 6.7 % to 65.0 + /- 7.3 % ( p < or = .002 ) and from 49.0 + /- 9.8 % to 69.6 + /- 6.5 % ( p < or = .04 ) , respectively . These absorptive changes result ed in a decrease in stool output ( 1,783 + /- 414 g/d control period vs 1,308 + /- 404 g/d third week of treatment , p < or = .05 ) . Treatment with diet alone did not influence nutrient absorption or stool output . CONCLUSIONS The combined administration of growth hormone , glutamine , and a modified diet enhanced nutrient absorption from the remnant bowel after massive intestinal resection . These changes occurred in a group of patients that had previously failed to adapt to the provision of enteral nutrients . This therapy may offer an alternative to long-term dependence on total parenteral nutrition for patients with severe short bowel syndrome BACKGROUND AND AIMS Animal studies have reported positive effects of glutamine on intestinal absorption and morphology ; human studies have been less convincing . The aim of this study was to evaluate the effects of glutamine and diet on intestinal morphology , motility , and absorption . METHODS A r and omized , double blind , placebo-controlled crossover study in 8 patients with short- Output:	The results suggest a positive effect of human growth hormone on weight gain and energy absorption . However , in the majority of trials , the effects are short-lived returning to baseline shortly after cessation of therapy . To date , the evidence is inconclusive to recommend this therapy .
MS21379	*TASK* the task is to summarize an input biomedical literature in six sentences *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 : There exists few pediatric data on the safety and efficacy of prophylactic antibiotics during chemotherapy-induced agranulocytosis . Methods : We prospect ively studied the incidence of infection-related fever in 38 children , aged 2 - 16 years , with acute myeloid leukemia ( AML ) over 121 chemotherapy treatment cycles . A prophylactic group ( n = 18 ) was given either vancomycin/cefepime ( 400 mg/m2 , q12 h/50 mg/kg , q12 h ) or piperacillin/tazobactam ( 110 mg/kg , q12 h ) . Control patients ( n = 20 ) received no preventive antibiotics . Results : The prophylactic group ( 59 treatment cycles ) experienced fever less frequently than the control group ( 0.4 vs. 0.9 events ; p < 0.001 ) , had a longer interval between agranulocytosis and fever ( 6.4 vs. 3.8 days ; p = 0.007 ) , had a shorter duration of hospitalization ( 21.5 vs. 28.5 days ; p < 0.001 ) , and had a lower rate of lung infection ( 38.8 vs. 80.0 % ; p < 0.001 ) . One patient taking vancomycin experienced a skin rash and 3 patients taking piperacillin/tazobactam had diarrhea ; these side effects subsided after antibiotics were discontinued . Conclusions : In children with AML , prophylactic antibiotics during the period of chemotherapy-induced agranulocytosis can effectively reduce the incidence of infectious fever and can shorten the average length of hospital stay , improving treatment success and quality of life PURPOSE To develop a score predicting the risk of adverse events ( AEs ) in pediatric patients with cancer who experience fever and neutropenia ( FN ) and to evaluate its performance . PATIENTS AND METHODS Pediatric patients with cancer presenting with FN induced by nonmyeloablative chemotherapy were observed in a prospect i ve multicenter study . A score predicting the risk of future AEs ( ie , serious medical complication , microbiologically defined infection , radiologically confirmed pneumonia ) was developed from a multivariate mixed logistic regression model . Its cross-vali date d predictive performance was compared with that of published risk prediction rules . Results An AE was reported in 122 ( 29 % ) of 423 FN episodes . In 57 episodes ( 13 % ) , the first AE was known only after re assessment after 8 to 24 hours of inpatient management . Predicting AE at re assessment was better than prediction at presentation with FN . A differential leukocyte count did not increase the predictive performance . The score predicting future AE in 358 episodes without known AE at re assessment used the following four variables : preceding chemotherapy more intensive than acute lymphoblastic leukemia maintenance ( weight = 4 ) , hemoglobin > or = 90 g/L ( weight = 5 ) , leukocyte count less than 0.3 G/L ( weight = 3 ) , and platelet count less than 50 G/L ( weight = 3 ) . A score ( sum of weights ) > or = 9 predicted future AEs . The cross-vali date d performance of this score exceeded the performance of published risk prediction rules . At an overall sensitivity of 92 % , 35 % of the episodes were classified as low risk , with a specificity of 45 % and a negative predictive value of 93 % . CONCLUSION This score , based on four routinely accessible characteristics , accurately identifies pediatric patients with cancer with FN at risk for AEs after re assessment PURPOSE To compare outcome and cost of ambulatory versus hospitalized management among febrile neutropenic children at low risk for invasive bacterial infection ( IBI ) . PATIENTS AND METHODS Children presenting with febrile neutropenia at six hospitals in Santiago , Chile , were categorized as high or low risk for IBI . Low-risk children were r and omly assigned after 24 to 36 hours of hospitalization to receive ambulatory or hospitalized treatment and monitored until episode resolution . Outcome and cost were determined for each episode and compared between both groups using predefined definitions and question naires . RESULTS A total of 161 ( 41 % ) of 390 febrile neutropenic episodes evaluated from June 2000 to February 2003 were classified as low risk , of which 149 were r and omly assigned to ambulatory ( n = 78 ) or hospital-based ( n = 71 ) treatment . In both groups , mean age ( ambulatory management , 55 months ; hospital-based management , 66 months ) , sex , and type of cancer were similar . Outcome was favorable in 74 ( 95 % ) of 78 ambulatory-treated children and 67 ( 94 % ) of 71 hospital-treated children ( P = NS ) . Mean cost of an episode was US 638 dollars ( 95 % CI , 572 dollars to 703 dollars ) and US 903 dollars ( 95 % CI , 781 dollars to 1,025 dollars ) for the ambulatory and hospital-based groups , respectively ( P = .003 ) . CONCLUSION For children with febrile neutropenia at low risk for IBI , ambulatory management is safe and significantly cost saving compared with st and ard hospitalized therapy A risk prediction model for invasive bacterial infection ( IBI ) was prospect ively evaluated among children presenting with cancer , fever , and neutropenia . The model incorporated assessment of 5 previously identified risk factors : serum level of C-reactive protein ( CRP ) > /=90 mg/L , hypotension , identification of relapse of leukemia as the cancer type , platelet count of < /=50,000 platelets/mm(3 ) , and recent receipt of chemotherapy [ 16 ] . Children were uniformly evaluated at enrollment and were classified as having high or low risk for IBI according to a model that considers the number and type of variables present . Of the 263 febrile episodes evaluated during a 17-month period , 140 ( 53 % ) were in IBI-positive children . The sensitivity , specificity , and positive and negative predictive values of the model were 92 % , 76 % , 82 % , and 90 % , respectively . Identification of these 5 risk factors during the first 24 h of hospitalization was helpful in discriminating between children with a high or low risk for IBI BACKGROUND Febrile neutropenia ( FN ) is a frequent , serious complication of intensive pediatric chemotherapy regimens . The aim of this trial was to compare quality of life ( QOL ) between inpatient and outpatient intravenous antibiotic management of children and adolescents with low risk febrile neutropenia ( LRFN ) . PROCEDURE In this r and omised non-blinded trial , patients between 1 and 21 years old , receiving low/moderate intensity chemotherapy were pre-consented and , on presentation to emergency ( ED ) with FN satisfying low risk criteria , r and omised to either outpatient or inpatient care with intravenous cefepime 50 mg/kg ( 12 hourly ) . All patients continued antibiotics for at least 48 hours , until afebrile for 24 hours and demonstrating a rising absolute neutrophil count ≥200/mm(3 ) . Several domains of QOL were examined by daily question naire . RESULTS Eighty-one patients presented to ED with 159 episodes of fever . Thirty-seven FN presentations involving 27 patients were r and omised to inpatient ( 18 ) and outpatient ( 19 ) management . Combined QOL mean scores for parents were higher for the outpatient group and scores for three specific parent variables ( keeping up with household tasks/time spent with partner/time spent with other children ) were higher among out patients . There was no difference in parent confidence/satisfaction in care between groups . Patients scored better in the outpatient group overall and for sleep and appetite . The mean length of fever was equivalent between groups and there were no serious adverse events attributable to cefepime or outpatient care . CONCLUSION Outpatient cefepime management of LRFN provided significant benefit to parents and patients across several QOL domains and appeared both feasible and safe During a 2-year period , all children with cancer , neutropenia , and fever who were admitted to Hospital de Niños Luis Calvo Mackenna ( Santiago , Chile ) were enrolled in a study of the safety of stopping antibiotic therapy on day 3 of treatment . Children who met predefined criteria for nonbacterial fever were r and omized on day 3 to stop ( group A ) or continue ( group B ) antibiotic therapy . A total of 220 children with cancer had 238 episodes of fever and neutropenia ; 68 children with 75 episodes met entry criteria for nonbacterial fever ( group A , 36 ; group B , 39 ) . Both groups were comparable in terms of age , gender , oncological disease , chemotherapy status , and initial neutrophil count . Resolution of symptoms occurred in 34 of 36 episodes in group A and 36 of 39 episodes in group B ( P > .05 ) . No deaths occurred , and bacterial superinfections were uncommon . For children with cancer as well as episodes of fever and neutropenia without an identifiable bacterial etiology at admission , stopping antibiotic therapy on day 3 was safe and not associated with a higher risk of bacterial superinfections Febrile neutropenia is a heterogeneous condition . Recently , several risk factors have been defined , permitting the definition of a lower risk group of patients who may benefit form less aggressive therapy . The use of an oral antibiotic approach was tested in the current trial AIM Empirical therapy for children with febrile neutropenia has traditionally consisted of combination antibiotics , usually a beta-lactam and an aminoglycoside . However , recent trends and international guidelines have now made monotherapy a feasible option in the management of this group of patients . We prospect ively evaluated the efficacy and safety of cefepime monotherapy in our population of paediatric cancer patients with febrile neutropenia . METHODS An audit was performed on children aged 16 years and younger presenting with fever and neutropenia who were managed with empirical single-agent cefepime . The patients were analysed for clinical outcome , documented infections and side-effects of the study drug . Success was defined as clinical improvement without treatment modification . Death or any change to the empirical antibiotic was considered as failure . RESULTS In this study 79 children ( median age 5.2 years ) with 133 episodes of febrile neutropenia were prospect ively studied between August 2004 and August 2005 . A microbiologically documented infection was seen in 26 episodes . The success rate of cefepime monotherapy was 60 % . The rate of survival through neutropenia ( with or without modification ) was 98 % . No significant adverse effects were seen . CONCLUSION Cefepime monotherapy is a safe and feasible option for treatment of childhood cancer patients with febrile neutropenia BACKGROUND The st and ard treatment of fever in chemotherapy-induced neutropenia ( FN ) includes emergency hospitalization and empirical intravenous antimicrobial therapy . This study determined if first-day step-down to oral outpatient treatment is not inferior to continued st and ard regarding safety and efficacy in children with low-risk FN . PROCEDURE In a r and omized controlled non-blinded multicenter study , pediatric patients with FN after non-myeloablative chemotherapy were reassessed after 8 - 22 hours of inpatient intravenous antimicrobial therapy . Low-risk patients were r and omized to first-day step-down to experimental ( outpatient , oral amoxicillin plus ciprofloxacin ) versus continued st and ard treatment . Exact non-inferiority tests were used for safety ( no serious medical complication ; non-inferiority margin of difference , 3.5 % ) and efficacy ( resolution of infection without recurrence , no modification of antimicrobial therapy , no adverse event ; 10 % ) . RESULTS In 93 ( 26 % ) of 355 potentially eligible FN episodes low-risk criteria were fulfilled , and 62 were r and omized , 28 to experimental ( 1 lost to follow-up ) and 34 to st and ard treatment . In intention-to-treat analyses , non-inferiority was not proven for safety [ 27 of 27 ( 100 % ) vs. 33 of 34 ( 97 % ; 1 death ) episodes ; 95 % upper confidence border , 6.7 % ; P = 0.11 ] , but non-inferiority was proven for efficacy [ 23 of 27 ( 85 % ) vs. 26 of 34 ( 76 % ) episodes ; 95 % upper confidence border , 9.4 % ; P = 0.045 ] . Per- protocol analyses confirmed these results . CONCLUSIONS In children with low-risk FN , the efficacy of first-day step-down to oral antimicrobial therapy with amoxicillin and ciprofloxacin in an outpatient setting was non-inferior to continued hospitalization and intravenous antimicrobial therapy . The safety of this procedure , however , was not assessable with sufficient power BACKGROUND Hospitalization with single or multi-agent antibiotic therapy has been the st and ard of care for treatment of febrile neutropenia in cancer patients . We hypothesized that an empiric antibiotic regimen that is effective and that can be administered once Output:	Evidently , there are still profound gaps regarding very early and early discharge in children with cancer and febrile neutropenia .
MS21380	*TASK* the task is to summarize an input biomedical literature in six sentences *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 efficacy of self-recording of blood pressure in the management of hypertension was assessed in a r and omized clinical trial involving 140 persons who had been receiving antihypertensive therapy for a year or more , but whose diastolic blood pressure had remained at 95 mm Hg or higher . To control for the increased attention implicit in self-recording , which might affect blood pressure , the patients were assigned at r and om to one of the four groups : self-recording and monthly home visits , self-recording only , monthly home visits only , and neither self-recording nor monthly home visits . This design also permitted assessment of the effect of home visits . During the 6-month experiment no significant differences were apparent between the groups in either compliance or diastolic blood pressure . However , both self-recording and monthly home visits produced a reduction in blood pressure among patients who admitted to difficulty remembering to take their pills ; a reduction was not seen among patients who said they had no such difficulty . This confirmed an earlier observation suggesting that this easily identified group of patients may be the most responsive to intervention programs Background —Hypertension is a leading mortality risk factor yet inadequately controlled in most affected subjects . Effective programs to address this problem are lacking . We hypothesized that an information technology – supported management program could help improve blood pressure ( BP ) control . Methods and Results —This r and omized controlled trial included 223 primary care hypertensive subjects with mean 24-hour BP > 130/80 and daytime BP > 135/85 mm Hg measured with ambulatory monitoring ( ABPM ) . Intervention subjects received a BP monitor and access to an information technology – supported adherence and BP monitoring system providing nurses , pharmacists , and physicians with monthly reports . Control subjects received usual care . The mean ( ±SD ) follow-up was 348 ( ±78 ) and 349 ( ±84 ) days in the intervention and control group , respectively . The primary end point of the change in the mean 24-hour ambulatory BP was consistently greater in intervention subjects for both systolic ( −11.9 versus −7.1 mm Hg ; P<0.001 ) and diastolic BP ( −6.6 versus −4.5 mm Hg ; P=0.007 ) . The proportion of subjects that achieved Canadian Guideline target BP ( 46.0 % versus 28.6 % ) was also greater in the intervention group ( P=0.006 ) . We observed similar BP declines for ABPM and self-recorded home BP suggesting the latter could be an alternative for confirming BP control . The intervention was associated with more physician-driven antihypertensive dose adjustments or changes in agents ( P=0.03 ) , more antihypertensive classes at study end ( P=0.007 ) , and a trend toward improved adherence measured by prescription refills ( P=0.07 ) . Conclusions —This multidisciplinary information technology – supported program that provided feedback to patients and healthcare providers significantly improved blood pressure levels in a primary care setting OBJECTIVE : To evaluate the effectiveness of a community pharmacist-based home blood pressure ( BP ) monitoring program . DESIGN : Trial of a high-intensity ( HI ) versus low-intensity ( LI ) intervention r and omized in 12 community pharmacies . The HI intervention comprised 4 face-to-face visits with a trained pharmacist . Pharmacists provided patient-specific education about hypertension . Following the first and third visits , patients were provided with a home BP monitoring device and instructed to measure their BP at least once daily for the next month . Home BP readings were used by the pharmacists to develop treatment recommendations for the patient ’s physician . Recommendations were discussed with the physician and , if approved , implemented by the pharmacist . In the LI intervention , pharmacists measured patients BP in the pharmacy and referred them to their physician for evaluation . PARTICIPANTS : Patients with uncontrolled BP at baseline . MEASUREMENTS : The main outcomes were the differences in systolic and diastolic BP ( SBP and DBP ) from baseline to follow-up between the HI and LI patients . RESULTS : The study enrolled 125 patients , 64 in the HI and 61 in the LI group . From baseline , SBP declined 13.4 mmHg in the HI group and 9.0 mmHg in the LI group . At the final visit , the difference in SBP/DBP change between the HI and LI group was −4.5/−3.2 mmHg ( P=.12 for SBP and P=.03 for DBP ) . CONCLUSIONS : The HI intervention achieved a lower DBP and this model could be a strategy for patients with hypertension Home blood pressure monitoring ( HBPM ) overcomes many of the limitations of traditional office blood pressure ( BP ) measurement and is both cheaper and easier to perform than ambulatory BP monitoring . Monitors that use the oscillometric method are currently available that are accurate , reliable , easy to use , and relatively inexpensive . An increasing number of patients are using them regularly to check their BP at home , but although this has been endorsed by national and international guidelines , detailed recommendations for their use have been lacking . There is a rapidly growing literature showing that measurements taken by patients at home are often lower than readings taken in the office and closer to the average BP recorded by 24-hour ambulatory monitors , which is the BP that best predicts cardiovascular risk . Because of the larger numbers of readings that can be taken by HBPM than in the office and the elimination of the white-coat effect ( the increase of BP during an office visit ) , home readings are more reproducible than office readings and show better correlations with measures of target organ damage . In addition , prospect i ve studies that have used multiple home readings to express the true BP have found that home BP predicts risk better than office BP ( class IIa ; level of evidence A ) . This call-to-action article makes the following recommendations : 1 ) It is recommended that HBPM should become a routine component of BP measurement in the majority of patients with known or suspected hypertension ; 2 ) Patients should be advised to purchase oscillometric monitors that measure BP on the upper arm with an appropriate cuff size and that have been shown to be accurate according to st and ard international protocol s. They should be shown how to use them by their healthcare providers ; 3 ) Two to three readings should be taken while the subject is resting in the seated position , both in the morning and at night , over a period of 1 week . A total of > /=12 readings are recommended for making clinical decisions ; 4 ) HBPM is indicated in patients with newly diagnosed or suspected hypertension , in whom it may distinguish between white-coat and sustained hypertension . If the results are equivocal , ambulatory BP monitoring may help to establish the diagnosis ; 5 ) In patients with prehypertension , HBPM may be useful for detecting masked hypertension ; 6 ) HBPM is recommended for evaluating the response to any type of antihypertensive treatment and may improve adherence ; 7 ) The target HBPM goal for treatment is < 135/85 mm Hg or < 130/80 mm Hg in high-risk patients ; 8) HBPM is useful in the elderly , in whom both BP variability and the white-coat effect are increased ; 9 ) HBPM is of value in patients with diabetes , in whom tight BP control is of paramount importance ; 10 ) Other population s in whom HBPM may be beneficial include pregnant women , children , and patients with kidney disease ; and 11 ) HBPM has the potential to improve the quality of care while reducing costs and should be reimbursed It is still uncertain whether one can safely base treatment decisions on self-measurement of blood pressure . In the present study , we investigated whether antihypertensive treatment based on self-measurement of blood pressure leads to the use of less medication without the loss of blood pressure control . We r and omly assigned 430 hypertensive patients to receive treatment either on the basis of self-measured pressures ( n=216 ) or office pressures ( OPs ; n=214 ) . During 1-year follow-up , blood pressure was measured by office measurement ( 10 visits ) , ambulatory monitoring ( start and end ) , and self-measurement ( 8 times , self-pressure group only ) . In addition , drug use , associated costs , and degree of target organ damage ( echocardiography and microalbuminuria ) were assessed . The self-pressure group used less medication than the OP group ( 1.47 versus 2.48 drug steps ; P<0.001 ) with lower costs ( $ 3222 versus $ 4420 per 100 patients per month ; P<0.001 ) but without significant differences in systolic and diastolic OP values ( 1.6/1.0 mm Hg ; P=0.25/0.20 ) , in changes in left ventricular mass index ( -6.5 g/m(2 ) versus -5.6 g/m(2 ) ; P=0.72 ) , or in median urinary microalbumin concentration ( -1.7 versus -1.5 mg per 24 hours ; P=0.87 ) . Nevertheless , 24-hour ambulatory blood pressure values at the end of the trial were higher in the self-pressure than in the OP group : 125.9 versus 123.8 mm Hg ( P<0.05 ) for systolic and 77.2 versus 76.1 mm Hg ( P<0.05 ) for diastolic blood pressure . These data show that self-measurement leads to less medication use than office blood pressure measurement without leading to significant differences in OP values or target organ damage . Ambulatory values , however , remain slightly elevated for the self-pressure group BACKGROUND St and ard office-based approaches to controlling hypertension show limited success . Such suboptimal hypertension control reflects in part the absence of both an infrastructure for patient education and frequent , regular blood pressure ( BP ) monitoring . We tested the efficacy of a physician-directed , nurse-managed , home-based system for hypertension management with st and ardized algorithms to modulate drug therapy , based on patients ' reports of home BP . METHODS We r and omized out patients requiring drug therapy for hypertension according to the Joint National Committee on Prevention , Detection , Evaluation , and Treatment of High Blood Pressure ( JNC VI ) criteria to receive usual medical care only ( UC , n = 76 ) or usual care plus nurse care management intervention ( INT , n = 74 ) over a 6-month period . RESULTS Patients receiving INT achieved greater reductions in office BP values at 6 months than those receiving UC : 14.2 + /- 18.1 versus 5.7 + /- 18.7 mm Hg systolic ( P < .01 ) and 6.5 + /- 10.0 versus 3.4 + /- 7.9 mm Hg diastolic , respectively ( P < .05 ) . At 6 months , we observed one or more changes in drug therapy in 97 % of INT patients versus 43 % of UC patients , and 70 % of INT patients received two or more drugs versus 46 % of UC . Average daily adherence to medication , measured by electronic drug event monitors , was superior among INT subjects ( mean + /- SD , 80.5 % + /- 23.0 % ) than among UC subjects ( 69.2 + /- 31.1 % ; t(113 ) = 2.199 , P = .03 ) . There were no significant adverse drug reactions in either group . CONCLUSIONS Telephone-mediated nurse management can successfully address many of the systems-related and patient-related issues that limit pharmacotherapeutic effectiveness for hypertension BACKGROUND Telemedicine is a promising but largely unproven technology for providing case management services to patients with chronic conditions who experience barriers to access to care or a high burden of illness . METHODS The authors conducted a r and omized , controlled trial comparing telemedicine case management to usual care , with blinding of those obtaining outcome data , in 1,665 Medicare recipients with diabetes , aged 55 years or greater , and living in federally design ated medically underserved areas of New York State . The primary endpoints were HgbA1c , blood pressure , and low-density lipoprotein ( LDL ) cholesterol levels . RESULTS In the intervention group ( n = 844 ) , mean HgbA1c improved over one year from 7.35 % to 6.97 % and from 8.35 % to 7.42 % in the subgroup with baseline HgbA1c > or = 7 % ( n = 353 ) . In the usual care group ( n = 821 ) mean HgbA1c improved over one year from 7.42 % to 7.17 % . Adjusted net reductions ( one-year minus baseline mean values in each group , compared between groups ) favoring the intervention were as follows : HgbA1c , 0.18 % ( p = 0.006 ) , systolic and diastolic blood pressure , 3.4 ( p = 0.001 ) and 1.9 mm Hg ( p < 0.001 ) , and LDL cholesterol , 9.5 mg/dL ( p < 0.001 ) . In the subgroup with baseline HgbA1c > or = 7 % , net adjusted reduction in HgbA1c favoring the intervention group was 0.32 % ( p = 0.002 ) . Mean LDL cholesterol level in the intervention group at one year was 95.7 mg/dL. The intervention effects were similar in magnitude in the subgroups living in New York City and upstate New York . CONCLUSION Telemedicine case management improved glycemic control , blood pressure levels , and total and LDL cholesterol levels at one year of follow-up African Americans have a higher prevalence of hypertension and poorer cardi Output:	For SMBP monitoring plus additional support versus SMBP monitoring alone or with less intense additional support ( 13 comparisons ) , low-strength evidence fails to support a difference . Across all comparisons , evidence for clinical outcomes is insufficient . For other surrogate or intermediate outcomes , low-strength evidence fails to show differences . Self-measured BP monitoring with or without additional support lowers BP compared with usual care , but the BP effect beyond 12 months and long-term benefits remain uncertain . Additional support enhances the BP-lowering effect .
MS21381	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Summary Background We design ed the EURAMOS-1 trial to investigate whether intensified postoperative chemotherapy for patients whose tumour showed a poor response to preoperative chemotherapy ( ≥10 % viable tumour ) improved event-free survival in patients with high- grade osteosarcoma . Methods EURAMOS-1 was an open-label , international , phase 3 r and omised , controlled trial . Consenting patients with newly diagnosed , resectable , high- grade osteosarcoma aged 40 years or younger were eligible for r and omisation . Patients were r and omly assigned ( 1:1 ) to receive either postoperative cisplatin , doxorubicin , and methotrexate ( MAP ) or MAP plus ifosfamide and etoposide ( MAPIE ) using concealed permuted blocks with three stratification factors : trial group ; location of tumour ( proximal femur or proximal humerus vs other limb vs axial skeleton ) ; and presence of metastases ( no vs yes or possible ) . The MAP regimen consisted of cisplatin 120 mg/m2 , doxorubicin 37·5 mg/m2 per day on days 1 and 2 ( on weeks 1 and 6 ) followed 3 weeks later by high-dose methotrexate 12 g/m2 over 4 h. The MAPIE regimen consisted of MAP as a base regimen , with the addition of high-dose ifosfamide ( 14 g/m2 ) at 2·8 g/m2 per day with equidose mesna uroprotection , followed by etoposide 100 mg/m2 per day over 1 h on days 1–5 . The primary outcome measure was event-free survival measured in the intention-to-treat population . This trial is registered with Clinical Trials.gov , number NCT00134030 . Findings Between April 14 , 2005 , and June 30 , 2011 , 2260 patients were registered from 325 sites in 17 countries . 618 patients with poor response were r and omly assigned ; 310 to receive MAP and 308 to receive MAPIE . Median follow-up was 62·1 months ( IQR 46·6–76·6 ) ; 62·3 months ( IQR 46·9–77·1 ) for the MAP group and 61·1 months ( IQR 46·5–75·3 ) for the MAPIE group . 307 event-free survival events were reported ( 153 in the MAP group vs 154 in the MAPIE group ) . 193 deaths were reported ( 101 in the MAP group vs 92 in the MAPIE group ) . Event-free survival did not differ between treatment groups ( hazard ratio [ HR ] 0·98 [ 95 % CI 0·78–1·23 ] ) ; hazards were non-proportional ( p=0·0003 ) . The most common grade 3–4 adverse events were neutropenia ( 268 [ 89 % ] patients in MAP vs 268 [ 90 % ] in MAPIE ) , thrombocytopenia ( 231 [ 78 % in MAP vs 248 [ 83 % ] in MAPIE ) , and febrile neutropenia without documented infection ( 149 [ 50 % ] in MAP vs 217 [ 73 % ] in MAPIE ) . MAPIE was associated with more frequent grade 4 non-haematological toxicity than MAP ( 35 [ 12 % ] of 301 in the MAP group vs 71 [ 24 % ] of 298 in the MAPIE group ) . Two patients died during postoperative therapy , one from infection ( although their absolute neutrophil count was normal ) , which was definitely related to their MAP treatment ( specifically doxorubicin and cisplatin ) , and one from left ventricular systolic dysfunction , which was probably related to MAPIE treatment ( specifically doxorubicin ) . One suspected unexpected serious adverse reaction was reported in the MAP group : bone marrow infa rct ion due to methotrexate . Interpretation EURAMOS-1 results do not support the addition of ifosfamide and etoposide to postoperative chemotherapy in patients with poorly responding osteosarcoma because its administration was associated with increased toxicity without improving event-free survival . The results define st and ard of care for this population . New strategies are required to improve outcomes in this setting . Funding UK Medical Research Council , National Cancer Institute , European Science Foundation , St Anna Kinderkrebsforschung , Fonds National de la Recherche Scientifique , Fonds voor Wetenschappelijk Onderzoek-Vla and eren , Parents Organization , Danish Medical Research Council , Academy of Finl and , Deutsche Forschungsgemeinschaft , Deutsche Krebshilfe , Federal Ministry of Education and Research , Semmelweis Foundation , ZonMw ( Council for Medical Research ) , Research Council of Norway , Sc and inavian Sarcoma Group , Swiss Paediatric Oncology Group , Cancer Research UK , National Institute for Health Research , University College London Hospitals , and Biomedical Research Centre The case histories of all patients with osteosarcoma of the trunk entered into the consecutive studies COSS 80 through COSS 86 of the Cooperative German/Austrian Osteosarcoma Study Group ( COSS ) were analyzed in order to evaluate their clinical characteristics and the impact of modern neoadjuvant therapy on prognosis . They were compared to those of all patients with extremity osteosarcoma treated according to the same protocol s. While tumors of the trunk comprised only 32 ( 4.8 % ) of 665 primary classical osteosarcomas , secondary osteosarcomas were much more likely to be located in bones of the axial skeleton ( 6 of 18 , 33 % ) . Patients with primary osteosarcoma of the axial skeleton were older ( mean : 20.8 vs. 15.2 years , P < 0.01 ) and were more likely to present with metastases at diagnosis ( 34 % vs 12 % , P < 0.001 ) than those with primary extremity osteosarcoma . In contrast to extremity tumors , local surgical treatment failure was very common in osteosarcomas of the trunk . Complete tumor removal was achieved in less than half of all evaluable cases . The prognosis of eight patients with localized primary axial osteosarcoma and effective surgical local control was not inferior to that of 483 equally evaluable patients with extremity tumors . In conclusion , while secondary systemic spread of axial osteosarcoma may be avoided in patients treated with multiagent chemotherapy , successful treatment is often barred by primary metastatic disease and inability to control the local tumor site PURPOSE To determine whether the addition of ifosfamide and /or muramyl tripeptide ( MTP ) encapsulated in liposomes to cisplatin , doxorubicin , and high-dose methotrexate ( HDMTX ) could improve the probability for event-free survival ( EFS ) in newly diagnosed patients with osteosarcoma ( OS ) . PATIENTS AND METHODS Six hundred seventy-seven patients with OS without clinical ly detectable metastatic disease were treated with one of four prospect ively r and omized treatments . All patients received identical cumulative doses of cisplatin , doxorubicin , and HDMTX and underwent definitive surgical resection of the primary tumor . Patients were r and omly assigned to receive or not to receive ifosfamide and /or MTP in a 2 double dagger 2 factorial design . The primary end point for analysis was EFS . RESULTS Patients treated with the st and ard arm of therapy had a 3-year EFS of 71 % . We could not analyze the results by factorial design because we observed an interaction between the addition of ifosfamide and the addition of MTP . The addition of MTP to st and ard chemotherapy achieved a 3-year EFS rate of 68 % . The addition of ifosfamide to st and ard chemotherapy achieved a 3-year EFS rate of 61 % . The addition of both ifosfamide and MTP result ed in a 3-year EFS rate of 78 % . CONCLUSION The addition of ifosfamide in this dose schedule to st and ard chemotherapy did not enhance EFS . The addition of MTP to chemotherapy might improve EFS , but additional clinical and laboratory investigation will be necessary to explain the interaction between ifosfamide and MTP We conducted a r and omized controlled trial to determine whether intensive multi-agent adjuvant chemotherapy improves the chances of relapse-free survival in patients with nonmetastatic high- grade osteosarcoma of the extremity , as compared with concurrent controls . After undergoing definitive surgery , 36 patients were r and omly assigned to adjuvant chemotherapy or to observation without adjuvant treatment . At two years the actuarial relapse-free survival was 17 percent in the control group , similar to that found in studies before 1970 , and 66 percent in the adjuvant-chemotherapy group ( P less than 0.001 ) . Similar results were observed among 77 additional patients who declined to undergo r and omization but who elected observation or chemotherapy . We conclude that the natural history of osteosarcoma of the extremity has remained stable over the past two decades , that adjuvant chemotherapy increases the chances of relapse-free survival of patients with high- grade osteosarcoma , and that it should be given to all such patients PURPOSE To define prognostic factors for response and long-term outcome for a wide spectrum of osteosarcomas , extending well beyond those of the typical young patient with seemingly localized extremity disease . PATIENTS AND METHODS A total of 1,702 consecutive newly diagnosed patients with high- grade osteosarcoma of the trunk or limbs registered into the neoadjuvant studies of the Cooperative Osteosarcoma Study Group before July 1998 were entered into an analysis of demographic , tumor-related , and treatment-related variables , response , and survival . The intended therapeutic strategy included preoperative and postoperative chemotherapy with multiple agents as well as surgery of all operable lesions . RESULTS Axial tumor site , male sex , and a long history of symptoms were associated with poor response to chemotherapy in univariate and multivariate analysis . Actuarial 10-year overall and event-free survival rates were 59.8 % and 48.9 % . Among the variables assessable at diagnosis , patient age ( actuarial 10-year survival > or = 40 , 41.6 % ; < 40 , 60.2 % ; P = .012 ) , tumor site ( axial , 29.2 % ; limb , 61.7 % ; P < .0001 ) , and primary metastases ( yes , 26.7 % ; no , 64.4 % ; P < .0001 ) , and for extremity osteosarcomas , also size ( > or = one third , 52.5 % ; < one third , 66.7 % ; P < .0001 ) and location within the limb ( proximal , 49.3 % ; other , 63.9 % ; P < .0001 ) , had significant influence on outcome . Two additional important prognostic factors were treatment related : response to chemotherapy ( poor , 47.2 % ; good , 73.4 % ; P < .0001 ) and the extent of surgery ( incomplete , 14.6 % ; macroscopically complete , 64.8 % ; P < .0001 ) . All factors except age maintained their significance in multivariate testing , with surgical remission and histologic response emerging as the key prognostic factors . CONCLUSION Tumor site and size , primary metastases , response to chemotherapy , and surgical remission are of independent prognostic value in osteosarcoma Background High- grade osteosarcoma is a primary malignant bone tumour mainly affecting children and young adults . The European and American Osteosarcoma Study (EURAMOS)-1 is a collaboration of four study groups aim ing to improve outcomes of this rare disease by facilitating r and omised controlled trials . Methods Patients eligible for EURAMOS-1 were aged ≤40 years with M0 or M1 skeletal high- grade osteosarcoma in which case complete surgical resection at all sites was deemed to be possible . A three-drug combination with methotrexate , doxorubicin and cisplatin was defined as st and ard chemotherapy , and between April 2005 and June 2011 , 2260 patients were registered . We report survival outcomes and prognostic factors in the full cohort of registered patients . Results For all registered patients at a median follow-up of 54 months ( interquartile range : 38–73 ) from biopsy , 3-year and 5-year event-free survival were 59 % ( 95 % confidence interval [ CI ] : 57–61 % ) and 54 % ( 95 % CI : 52–56 % ) , respectively . Multivariate analyses showed that the most adverse factors at diagnosis were pulmonary metastases ( hazard ratio [ HR ] = 2.34 , 95 % CI : 1.95–2.81 ) , non-pulmonary metastases ( HR = 1.94 , 95 % CI : 1.38–2.73 ) or an axial skeleton tumour site ( HR = 1.53 , 95 % CI : 1.10–2.13 ) . The histological subtypes telangiectatic ( HR Output:	Age , tumor location , tumor size/volume , and histologic response carried independent prognostic value in the majority of the studies .
MS21382	*TASK* the task is to summarize an input biomedical literature in six sentences *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 benefit of chemotherapy in patients with symptomatic hormone-resistant prostate cancer using relevant end points of palliation in a r and omized controlled trial . PATIENTS AND METHODS We r and omized 161 hormone-refractory patients with pain to receive mitoxantrone plus prednisone or prednisone alone ( 10 mg daily ) . Nonresponding patients on prednisone could receive mitoxantrone subsequently . The primary end point was a palliative response defined as a 2-point decrease in pain as assessed by a 6-point pain scale completed by patients ( or complete loss of pain if initially 1 + ) without an increase in analgesic medication and maintained for two consecutive evaluations at least 3 weeks apart . Secondary end points were a decrease of > or = 50 % in use of analgesic medication without an increase in pain , duration of response , and survival . Health-related quality of life was evaluated with a series of linear analog self- assessment scales ( LASA and the Prostate Cancer-Specific Quality -of-Life Instrument [ PROSQOLI ] ) , the core question naire of the European Organization for Research and Treatment of Cancer ( EORTC ) , and a disease-specific module . RESULTS Palliative response was observed in 23 of 80 patients ( 29 % ; 95 % confidence interval , 19 % to 40 % ) who received mitoxantrone plus prednisone , and in 10 of 81 patients ( 12 % ; 95 % confidence interval , 6 % to 22 % ) who received prednisone alone ( P = .01 ) . An additional seven patients in each group reduced analgesic medication > or = 50 % without an increase in pain . The duration of palliation was longer in patients who received chemotherapy ( median , 43 and 18 weeks ; P < .0001 , log-rank ) . Eleven of 50 patients r and omized to prednisone treatment responded after addition of mitoxantrone . There was no difference in overall survival . Treatment was well tolerated , except for five episodes of possible cardiac toxicity in 130 patients who received mitoxantrone . Most responding patients had an improvement in quality -of-life scales and a decrease in serum prostate-specific antigen ( PSA ) level . CONCLUSION Chemotherapy with mitoxantrone and prednisone provides palliation for some patients with symptomatic hormone-resistant prostate cancer The Qualitator is a daily diary card to measure Quality of Life , developed for use in chemotherapy trials for patients with advanced breast cancer . In a trial at King 's College Hospital , 29 patients completed the Qualitator and their scores were compared with scores in the Linear Analogue Self- Assessment and Nottingham Health Profile taken four-weekly . In a separate study at Guy 's Hospital , 31 patients completed the diary . The Qualitator offers accurate prognostic data regarding subsequent UICC response and survival and is simple to use The objective of this study is to evaluate whether patient-reported baseline health-related quality of life ( HRQL ) measured by the Functional Assessment of Cancer Therapy-General ( FACT-G ) instrument is predictive of survival for patients with advanced lung cancer . Methods : Consecutive patients with advanced lung cancer planning to undergo palliative chemotherapy in the outpatient clinics of a Canadian tertiary care cancer centre were enrolled on study . FACT-G total scores and clinical predictors of survival ( age , sex , histology , stage of disease , previous weight loss , presence of liver metastases and performance status ) were prospect ively collected at baseline . Survival data was subsequently collected retrospectively from the Alberta Cancer Registry . Stratified Cox Proportional Hazards analysis was done examining the influence of baseline total FACT-G scores on survival , controlling for potential clinical confounders . Results : Median survival of the 42 patient cohort was 9.9 months with a 2-year survival of 16.7 % . Multivariate analysis indicated that baseline FACT-G total score is significantly associated with survival ( p= 0.004 ) . Conclusion : Baseline HRQL is a statistically significant predictor of survival for patients with advanced lung cancer . When used along with traditional clinical factors , patient-reported baseline HRQL assessment using the FACT-G provides additional prognostic information to the patient and clinician BACKGROUND The psychological response to breast cancer , such as a fighting spirit or an attitude of helplessness and hopelessness toward the disease , has been suggested as a prognostic factor with an influence on survival . We have investigated the effect of psychological response on disease outcome in a large cohort of women with early-stage breast cancer . METHODS 578 women with early-stage breast cancer were enrolled in a prospect i ve survival study . Psychological response was measured by the mental adjustment to cancer ( MAC ) scale , the Courtauld emotional control ( CEC ) scale , and the hospital anxiety and depression ( HAD ) scale 4 - 12 weeks and 12 months after diagnosis . The women were followed up for at least 5 years . Cox 's proportional-hazards regression was used to obtain the hazard ratios for the measures of psychological response , with adjustment for known clinical factors associated with survival . FINDINGS At 5 years , 395 women were alive and without relapse , 50 were alive with relapse , and 133 had died . There was a significantly increased risk of death from all causes by 5 years in women with a high score on the HAD scale category of depression ( hazard ratio 3.59 [ 95 % CI 1.39 - 9.24 ] ) . There was a significantly increased risk of relapse or death at 5 years in women with high scores on the helplessness and hopelessness category of the MAC scale compared with those with a low score in this category ( 1.55 [ 1.07 - 2.25 ] ) . There were no significant results found for the category of " fighting spirit " . INTERPRETATION For 5-year event-free survival a high helplessness/hopelessness score has a moderate but detrimental effect . A high score for depression is linked to a significantly reduced chance of survival ; however , this result is based on a small number of patients and should be interpreted with caution Measurement of health-related quality of life was integrated into a r and omized trial ( NMSG 4/90 ) comparing melphalan/prednisone to melphalan/prednisone + interferon alpha-2b in newly diagnosed multiple myeloma . One of the aims of the study was to assess the prognostic significance of quality -of-life scores , using the EORTC QLQ-C30 question naire . Univariate analysis showed a highly significant association with survival from the start of therapy for physical functioning as well as role and cognitive functioning , global quality of life , fatigue and pain . In multivariate analysis , physical functioning and W.H.O. performance status were independent prognostic factors ( P values = 0.001 for both ) when analysed in a Cox regression model with the somatic variables beta-2 microglobulin , skeletal disease and age . The best prediction for survival from the start of therapy was obtained by combining the beta-2 microglobulin and physical functioning scores in a variable consisting of three risk factor levels with an estimated median survival of 17 , 29 and 49 months , respectively . At a 12 months l and mark analysis , the relative risk for patients with physical functioning score 0 - 20 v 80 - 100 was 5.63 ( 99 % CI 2.76 - 11.49 ) , whereas the relative risk for patients without an objective response to chemotherapy compared to those with at least a minor response was 2.32 ( 99 % CI 1.44 - 3.74 ) . Quality -of-life assessment may be an independent and valuable addition to the known prognostic factors in multiple myeloma PURPOSE Evidence that psychosocial status and health-related quality of life ( HRQOL ) are associated with breast cancer ( BC ) outcomes is weak and inconsistent . We examined prognostic effects of these factors in a prospect i ve cohort study . PATIENTS AND METHODS Three hundred ninety-seven women with surgically resected T1 to T3 , N0/N1 , M0 BC completed the European Organization for Research and Treatment of Cancer Quality of Life Question naire ( Core 30 items ) , Profile of Mood States , Psychosocial Adjustment to Illness Scale , Impact of Events Scale , Mental Adjustment to Cancer Scale , and the Courtauld Emotional Control Scale 2 months after diagnosis and 1 year later . Data on tumor-related factors , treatment , and outcomes were obtained prospect ively from medical records , and Cox survival analyses were performed . RESULTS Mean age was 52.0 + /- 9.9 years . Two hundred twenty-five women had T1 , 136 women had T2 , 16 women had T3 , and 20 women had TX tumors ; 127 were N1 . One hundred thirteen women received adjuvant chemotherapy , 130 received hormone therapy , 45 received both , and 109 received neither . We investigated 140 prognostic associations ; four were found to be statistically significant at a P value of < /= .05 ( three fewer than expected by chance ) . Two were in the hypothesized direction of effect , and two were in the opposite direction . All arose from measurements 1 year after diagnosis , which were most susceptible to confounding by treatment . There was no evidence of consistency of associations across outcomes or question naires . These results are in keeping with chance as the explanation for our statistically significant findings . CONCLUSION HRQOL and psychosocial status at diagnosis and 1 year later are not associated with medical outcome in women with early-stage BC PURPOSE We observed that quality -of-life ( QL ) scores , collected to evaluate treatment in a r and omized trial in advanced breast cancer , predicted survival duration . This report explores the prognostic associations between QL and survival in more detail . PATIENTS AND METHODS In a r and omized clinical trial comparing intermittent and continuous therapy policies for patients with advanced breast cancer , QL was measured by linear analog self- assessment ( LASA ) and the Quality -of-Life Index ( QLI ) . Baseline scores and subsequent changes were included in statistical models of survival duration , with and without other prognostic factors . RESULTS Physician assessment of QLI and patient LASA scores for physical well-being ( PWB ) , mood , nausea and vomiting , appetite , and overall QL ( but not pain ) at the commencement of treatment were significant predictors of subsequent survival . Scores for PWB and QLI were independent of other prognostic factors . Changes in scores were also prognostically important . Both baseline and change in scores for PWB , mood , pain , and QLI after the first three treatment cycles , but before an arbitrary 180-day time point , were significantly predictive of survival beyond that time . Both QLI and PWB were prognostically independent of tumor response . Although QL improvement was correlated with tumor response , continuous therapy yielded significantly better QL scores , even in nonresponders . CONCLUSION These findings support the validity of the simple QL measures used in the trial . They are compatible with the simple explanation that patients perceive disease progression before it is clinical ly evident , but also with a causal relationship between QL and survival duration Background This paper describes the ethnic and socioeconomic correlates of functioning in a cohort of long-term nonrecurring breast cancer survivors . Methods Participants ( n = 804 ) in this study were women from the Health , Eating , Activity , and Lifestyle ( HEAL ) Study , a population -based , multicenter , multiethnic , prospect i ve study of women newly diagnosed with in situ or Stages I to IIIA breast cancer . Measurements occurred at three timepoints following diagnosis . Outcomes included st and ardized measures of functioning ( MOS SF-36 ) . Results Overall , these long-term survivors reported values on two physical function subscales of the SF-36 slightly lower than population norms . Black women reported statistically significantly lower physical functioning ( PF ) scores ( P = 0.01 ) , compared with White and Hispanic women , but higher mental health ( MH ) scores ( P < 0.01 ) compared with White and Hispanic women . In the final adjusted model , race was significantly related to PF , with Black participants and participants in the “ Other ” ethnic category reporting poorer functioning compared to the White referent group ( P < 0.01 , 0.05 ) . Not working outside the home , being retired or disabled and being unemployed ( on leave , looking for work ) were associated with poorer PF compared to currently working ( both P < 0.01 ) . Conclusion These data indicate that race/ethnicity influences psychosocial functioning in breast cancer survivors and can be used to identify need for targeted interventions to improve functioning Aim The aims of our study were to assess quality of life ( QoL ) as a prognostic factor of overall survival ( OS ) and to determine whether QoL data improved three prognostic classifications among French patients with advanced hepatocellular carcinoma ( HCC ) . Methods We pooled two r and omized clinical trials conducted by the Fédération Francophone de Cancérologie Digestive in a palliative setting . In each trial QoL was assessed at baseline using the Spitzer QoL Index ( 0–10 ) . Three prognostic classifications were calculated : Okuda , Cancer of the Liver Italian Program ( CLIP ) , and Barcelona Clinic Liver Cancer group ( BCLC ) scores . To explore whether the scores could be improved by including QoL , univariate Cox analyses of all potential baseline predictors were performed . A final multivariate Cox model was constructed including only significant multivariate baseline variables likely to result in improvement of each scoring system . In order to retain the best prognostic variable to add for each score , we compared Akaike information criterion , likelihood ratio , and Output:	With few exceptions , the findings showed that quality of life data or some aspects of quality of life measures were significant independent predictors of survival duration . Global quality of life , functioning domains and symptom scores - such as appetite loss , fatigue and pain - were the most important indicators , individually or in combination , for predicting survival times in cancer patients after adjusting for one or more demographic and known clinical prognostic factors . Conclusion This review provides evidence for a positive relationship between quality of life data or some quality of life measures and the survival duration of cancer patients . Pre-treatment ( baseline ) quality of life data appeared to provide the most reliable information for helping clinicians to establish prognostic criteria for treating their cancer patients . This strategy is likely to yield more accurate and specific quality of life-related prognostic variables for specific cancers
MS21383	*TASK* the task is to summarize an input biomedical literature in six sentences *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 prospect ively evaluate health-related quality of life ( HRQOL ) outcomes for uterine artery embolization ( UAE ) and hysterectomy up to 24 months after the intervention in terms of mental and physical health , urinary and defecatory function , and overall patient satisfaction . MATERIAL S AND METHODS Ethics committee approval and informed consent were obtained for the Embolisation versus Hysterectomy Trial . Women ( n = 177 ) with uterine fibroids and heavy menstrual bleeding who were scheduled to undergo hysterectomy were r and omly assigned to undergo UAE ( n = 88 ) or hysterectomy ( n = 89 ) . HRQOL was measured six times during a 24-month follow-up period with the following vali date d question naires : Medical Outcome Study Short Form 36 ( SF-36 ) mental component summary ( MCS ) and physical component summary ( PCS ) , Health Utilities Index Mark 3 , EuroQol 5D , urogenital distress inventory ( UDI ) , incontinence impact question naire , and defecation distress inventory ( DDI ) . Satisfaction was assessed with a seven-point Likert scale . Repeated measurement analysis was performed for between-group analysis . Paired t tests were performed for within-group analysis . Satisfaction was analyzed with the Fisher exact test . RESULTS The SF-36 MCS and PCS , Health Utilities Index Mark 3 , EuroQol 5D , and UDI scores were improved significantly in both groups at 6 months and afterward ( P < .05 ) . The DDI score was improved significantly in only the UAE group at 6 months and afterward ( P < .05 ) . No differences between groups were observed , with the exception of PCS scores at 6-week follow-up : Patients in the UAE group had significantly better scores than did patients in the hysterectomy group ( P < .001 ) . Improvement in PCS score at 24-month follow-up was significantly higher for patients who were employed at baseline ( P = .035 ) . At 24-month follow-up , patients in the hysterectomy group were significantly more satisfied than those in the UAE group ( P = .02 ) . CONCLUSION Both UAE and hysterectomy improved HRQOL . No differences were observed between groups regarding HRQOL at 24-month follow-up . On the basis of HRQOL results , the authors determined that UAE is a good alternative to hysterectomy OBJECTIVE The purpose of this study was to evaluate the long-term outcomes of uterine artery embolization using only gelatin sponge particles for symptomatic fibroids . MATERIAL S AND METHODS As part of an ongoing study of the procedure for fibroids , prospect i ve data of the initial 96 consecutive women treated between December 1997 and December 2001 , were collected in January 2005 . It had been more than 3 years since embolization in all cases . The follow-up period ranged from 4 to 60 months ( mean , 37.4 months ) . On the basis of serial question naires , we investigated the cumulative rates of symptom control , gynecologic interventions , and overall failure , using the Kaplan-Meier product limit estimator . Symptom control was defined as meaning patients whose symptoms had improved as indicated on the last question naire and who had not undergone any further gynecologic intervention because of symptoms . Overall failure was defined as meaning the patients who indicated that there had been no symptom improvement or recurrence or that they had undergone further gynecologic interventions . RESULTS Of all 96 women , 16 ( 17 % ) were lost to follow-up during the period . Cumulative rates of symptom control were 96.9 % at 1 year , 89.5 % at 3 years , and 89.5 % at 5 years . Cumulative rates of complications related to the gynecologic intervention and overall gynecologic interventions were 2.1 % and 4.2 % , respectively , at 1 year , 2.1 % and 5.4 % at 3 years , and 2.1 % and 10.5 % at 5 years . Cumulative rates of overall failure were 4.2 % at 1 year , 12.7 % at 3 years , and 12.7 % at 5 years . Major complications were noted in 3.1 % ( 3/96 ) . Of these three women , two required hospitalization for transvaginal resection of sloughing fibroids and one developed sexual dysfunction . Two women became pregnant , but both pregnancies result ed in miscarriage . CONCLUSION Uterine artery embolization using gelatin sponge particles alone can achieve long-term symptom control for fibroids in most cases AIM The purpose of this study was to compare the depth of vascular penetration of non-spherical polyvinyl alcohol ( PVA ) versus trisacryl gelatin microspheres ( MS ) in women undergoing uterine artery embolization ( UAE ) immediately before transabdominal myomectomy . MATERIAL S AND METHODS A total of 17 patients who had been referred for embolization before myomectomy underwent bilateral uterine artery embolization using either 355 - 500 microm PVA ( group A ) or 700 - 900 microm MS ( group B ) . The depth of penetration of the particles was assessed by identifying their presence and location in the resected specimen . RESULTS Of the 17 women enrolled in this study , 10 were in group A and 6 in group B. One woman underwent embolization using both types of particle and was excluded from the analysis . Embolic particles were significantly ( p = 0.048 ) more frequently located within the fibroid ( 4/6 , 67 % ) in Group B than Group A ( 1/10 , 10 % ) . Particles were also identified in the perifibroid tissues in 4/6 ( 67 % ) in Group B and 4/10 ( 40 % ) in Group A , with no statistical difference . There were no procedural complications . CONCLUSION MS particles ( 700 - 900 microm ) penetrate significantly deeper into leiomyomata compared with non-spherical PVA ( 355 - 500 microm ) . MS may therefore confer advantages in UAE , as they may more specifically target the fibroid , allowing an earlier end-point to embolization and minimizing ischaemic damage to normal myometrium and ovaries BACKGROUND The efficacy and safety of uterine-artery embolization , as compared with st and ard surgical methods , for the treatment of symptomatic uterine fibroids remain uncertain . METHODS We conducted a r and omized trial comparing uterine-artery embolization and surgery in women with symptomatic uterine fibroids . The primary outcome was quality of life at 1 year of follow-up , as measured by the Medical Outcomes Study 36-Item Short-Form General Health Survey ( SF-36 ) . RESULTS Patients were r and omly assigned in a 2:1 ratio to undergo either uterine-artery embolization or surgery , with 106 patients undergoing embolization and 51 undergoing surgery ( 43 hysterectomies and 8 myomectomies ) . There were no significant differences between groups in any of the eight components of the SF-36 scores at 1 year . The embolization group had a shorter median duration of hospitalization than the surgical group ( 1 day vs. 5 days , P<0.001 ) and a shorter time before returning to work ( P<0.001 ) . At 1 year , symptom scores were better in the surgical group ( P=0.03 ) . During the first year of follow-up , there were 13 major adverse events in the embolization group ( 12 % ) and 10 in the surgical group ( 20 % ) ( P=0.22 ) , mostly related to the intervention . Ten patients in the embolization group ( 9 % ) required repeated embolization or hysterectomy for inadequate symptom control . After the first year of follow-up , 14 women in the embolization group ( 13 % ) required hospitalization , 3 of them for major adverse events and 11 for reintervention for treatment failure . CONCLUSIONS In women with symptomatic fibroids , the faster recovery after embolization must be weighed against the need for further treatment in a minority of patients . ( IS RCT N.org number , IS RCT N23023665 [ controlled-trials.com ] . PURPOSE To compare tris-acryl microspheres and polyvinyl alcohol ( PVA ) microspheres as embolic agents in uterine artery embolization ( UAE ) for uterine leiomyomas in terms of clinical outcome , inflammatory response , and adverse reactions . MATERIAL S AND METHODS A double-blinded r and omized controlled trial was performed , with 27 patients in the tris-acryl microsphere group and 29 in the PVA microsphere group . The primary endpoint was clinical success , defined as a 2-year freedom from subsequent surgery as a result of persistent or deteriorated symptoms . Secondary endpoints included ( i ) posttreatment leiomyoma enlargement , ( ii ) leiomyoma volume reduction at 3 and 9 months , ( iii ) significant residual intratumoral perfusion , ( iv ) increase in inflammatory and stress markers , ( v ) incidence of complications , and ( vi ) duration of hospital stay . RESULTS There was no statistically significant difference between the two groups in patient demographics , clinical presentation , initial tumor findings , change in inflammatory and stress markers after treatment , incidence of complications , and duration of hospital stay . Tris-acryl microspheres were associated with a higher rate of clinical success than PVA microspheres ( 96.3 % [ 26 of 27 ] vs 69 % [ 20 of 29 ] ; P = .012 ) , a lower incidence of posttreatment leiomyoma enlargement ( P = .030 ) , and a lower incidence of significant residual intratumoral perfusion ( P = .030 ) . CONCLUSIONS In the treatment of uterine leiomyomas , UAE with tris-acryl microspheres was associated with a higher clinical success rate , a lower incidence of tumor enlargement , and no significant differences in adverse reactions and inflammatory response compared with the use of PVA microspheres . Tris-acryl microspheres therefore represent the preferred agent for UAE of uterine leiomyomas Objective To evaluate the efficacy of acrylamido polyvinyl alcohol microspheres ( a-PVAM ) as an embolic agent for uterine artery embolization ( UAE ) compared with Tris-acryl gelatin microspheres ( TAGM ) . Design , Setting , Participants Prospect i ve r and omized double-blind noninferiority trial . Conducted at two sites both with regional UAE practice s. Forty-six women with symptomatic leiomyomas . InterventionUAE procedure was performed with either of the two embolic agents . Either 700–900-μm a-PVAM or 500–700-μm TAGM was used . Main Outcome Measures Changes in leiomyoma perfusion , overall uterine volume , and dominant leiomyomas volume measured by contrast-enhanced magnetic resonance imaging at 1 week , 3 months , and 6 months after UAE by a reader blinded to the embolic agent used . Changes in Uterine Fibroid Symptoms and Quality of Life question naire scores were measured at 3 , 6 , and 12 months after UAE . Results Forty-six patients were r and omized and treated under the study protocol ( a-PVAM n = 22 , TAGM n = 24 ) . There were no procedure-related complications . Two patients were excluded from analysis ( one technical failure of the procedure , one withdrawal from study ) . Successful ( > 90 % ) leiomyoma devascularization was observed in 81 % of subjects at 1 week after UAE , 97 % at 3 months after UAE , and 95 % at 6 months after UAE . No significant differences were observed in 14 of 15 outcome measurements , consistent with noninferiority . TAGM was slightly superior to a-PVAM on one comparison ( overall quality of life at 3 months after UAE ) PURPOSE To report the 12-month clinical and magnetic resonance ( MR ) imaging results of an ongoing two-center registry involving acrylamido polyvinyl alcohol ( PVA ) microspheres for uterine artery embolization ( UAE ) for leiomyomas . MATERIAL S AND METHODS A total of 69 patients underwent UAE with 500 - 700-microm , 700 - 900-microm , and 900 - 1,200-mum acrylamido PVA microspheres ( BeadBlock ) . Thirty-three patients underwent UAE with a limited embolization ( protocol A ) and 36 patients underwent UAE with stasis as the angiographic endpoint ( protocol B ) . Primary objectives were clinical efficacy measured by a leiomyoma-specific quality of life ( QOL ) question naire and infa rct ion rate of leiomyomas on early contrast agent-enhanced MR imaging . Secondary objectives were in-hospital complications , patient satisfaction , and frequency of clinical failure . RESULTS Bilateral embolization was technically successful in 68 of 69 patients . A significant decrease ( P < .001 ) in symptom severity and increase in health-related QOL was observed at 3 and 12 months with no significant differences between embolization protocol s. However , contrast agent-enhanced MR imaging showed a significantly lower rate of completely infa rct ed leiomyomas in protocol A compared with protocol B ( P < Output:	Results No evidence of superiority of any embolic agent was demonstrated . Conclusions This study confirms that the current evidence demonstrates superiority of Embospheres over spherical PVA but no reported differences in outcomes between any of the other agents .
MS21384	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Because neuroimaging studies have shown that cue-provoked smoking craving is associated with changes in the activity of the bilateral dorsolateral prefrontal cortex ( DLPFC ) , we aim ed to investigate whether a powerful technique of noninvasive brain stimulation , transcranial direct current stimulation ( tDCS ) , reduces cue-provoked smoking craving as indexed by a visual analog scale . METHOD We performed a r and omized , sham-controlled crossover study in which 24 subjects received sham and active tDCS ( anodal tDCS of the left and right DLPFC ) in a r and omized order . Craving was induced by cigarette manipulation and exposure to a smoking video . The study ran from January 2006 to October 2006 . RESULTS Smoking craving was significantly increased after exposure to smoking-craving cues ( p < .0001 ) . Stimulation of both left and right DLPFC with active , but not sham , tDCS reduced craving significantly when comparing craving at baseline and after stimulation , without ( p = .007 ) and with ( p = .005 ) smoking-craving cues . There were no significant mood changes in any of the conditions of stimulation . Adverse events were mild and distributed equally across all treatment conditions . CONCLUSIONS Our findings extend the results of a previous study on the use of brain stimulation to reduce craving , showing that cortical stimulation with tDCS is beneficial for reducing cue-provoked craving , and thus support the further exploration of this technique for smoking cessation BACKGROUND Functional neuroimaging studies have shown that specific brain areas are associated with alcohol craving including the dorsolateral prefrontal cortex ( DLPFC ) . We tested whether modulation of DLPFC using transcranial direct current stimulation ( tDCS ) could alter alcohol craving in patients with alcohol dependence while being exposed to alcohol cues . METHODS We performed a r and omized sham-controlled study in which 13 subjects received sham and active bilateral tDCS delivered to DLPFC ( anodal left/cathodal right and anodal right/cathodal left ) . For sham stimulation , the electrodes were placed at the same positions as in active stimulation ; however , the stimulator was turned off after 30s of stimulation . Subjects were presented videos depicting alcohol consumption to increase alcohol craving . RESULTS Our results showed that both anodal left/cathodal right and anodal right/cathodal left significantly decreased alcohol craving compared to sham stimulation ( p<0.0001 ) . In addition , we found that following treatment , craving could not be further increased by alcohol cues . CONCLUSIONS Our findings showed that tDCS treatment to DLPFC can reduce alcohol craving . These findings extend the results of previous studies using noninvasive brain stimulation to reduce craving in humans . Given the relatively rapid suppressive effect of tDCS and the highly fluctuating nature of alcohol craving , this technique may prove to be a valuable treatment strategy within the clinical setting We aim ed to assess whether modulation of the dorsolateral prefrontal cortex ( DLFPC ) with noninvasive brain stimulation , namely transcranial direct current stimulation ( tDCS ) , modifies food craving in healthy subjects . We performed a r and omized sham-controlled cross-over study in which 23 subjects received sham and active tDCS ( anode left/cathode right and anode right/cathode left ) of the DLPFC . Subjects were exposed to food and also watched a movie of food associated with strong craving . Desire for food consumption was evaluated by visual analogue scales ( VAS ) and food consumption before and after treatment . In addition we measured visual attention to food using an eye tracking system . Craving for viewed foods as indexed by VAS was reduced by anode right/cathode left tDCS . After sham stimulation , exposure to real food or food-related movie increased craving ; whereas after anode left/cathode right tDCS , the food-related stimuli did not increase craving levels , as revealed by the VAS scale . Moreover , compared with sham stimulation , subjects fixated food-related pictures less frequently after anode right/cathode left tDCS and consumed less food after both active stimulation conditions . These changes were not related to mood changes after any type of tDCS treatment . The effects of tDCS on food craving might be related to a modulation of neural circuits associated with reward and decision-making Drug-related cues induce craving , which may perpetuate drug use or trigger relapse in addicted individuals . Craving is also under the influence of other factors in daily life , such as drug availability and self-control . Neuroimaging studies using drug cue paradigms have shown frontal lobe involvement in this context ual influence on cue reactivity , but have not clarified how and which frontal area accounts for this phenomenon . We explored frontal lobe contributions to cue-induced drug craving under different intertemporal drug availability conditions by combining transcranial magnetic stimulation and functional magnetic resonance imaging in smokers . We hypothesized that the dorsolateral prefrontal cortex ( DLPFC ) regulates craving during changes in intertemporal availability . Subjective craving was greater when cigarettes were immediately available , and this effect was eliminated by transiently inactivating the DLPFC with transcranial magnetic stimulation . Functional magnetic resonance imaging demonstrated that the signal most proportional to subjective craving was located in the medial orbitofrontal cortex across all context s , whereas the DLPFC most strongly encoded intertemporal availability information . The craving-related signal in the medial orbitofrontal cortex was attenuated by inactivation of the DLPFC , particularly when cigarettes were immediately available . Inactivation of the DLPFC also reduced craving-related signals in the anterior cingulate and ventral striatum , areas implicated in transforming value signals into action . These findings indicate that DLPFC builds up value signals based on knowledge of drug availability , and support a model wherein aberrant circuitry linking dorsolateral prefrontal and orbitofrontal cortices may underlie addiction BACKGROUND Modulation of the serotonergic system affects long-term potentiation ( LTP ) and long-term depression ( LTD ) , the likely neurophysiologic derivates of learning and memory formation , in animals and slice preparations . Serotonin-dependent modulation of plasticity has been proposed as an underlying mechanism for depression . However , direct knowledge about the impact of serotonin on neuroplasticity in humans is missing . Here we explore the impact of the serotonin reuptake blocker citalopram on plasticity induced by transcranial direct current stimulation ( tDCS ) in humans in a single-blinded , placebo-controlled , r and omized crossover study . METHODS In 12 healthy subjects , anodal excitability-enhancing or cathodal excitability-diminishing tDCS was applied to the motor cortex under a single dose of 20-mg citalopram or placebo medication . Motor cortex excitability was monitored by single-pulse transcranial magnetic stimulation ( TMS ) . RESULTS Under placebo medication , anodal tDCS enhanced , and cathodal tDCS reduced , excitability for about 60 - 120 min . Citalopram enhanced and prolonged the facilitation induced by anodal tDCS , whereas it turned cathodal tDCS-induced inhibition into facilitation . CONCLUSIONS Serotonin has a prominent impact on neuroplasticity in humans , which is in favor for facilitatory plasticity . Taking into account serotonergic hypoactivity in depression , this might explain deficits of learning and memory formation . Moreover , the results suggest that for therapeutic brain stimulation in depression and other neuropsychiatric diseases ( e.g. , in neurorehabilitation ) , serotonergic reinforcement may enhance facilitatory aftereffects and thereby increase the efficacy of these tools Food craving can be defined as the " urge to eat a specific food " . Previous findings suggest impairment of inhibitory control , specifically a regulatory deficit in the lateral prefrontal circuitry that is associated with a compulsion for food . As demonstrated by three previous studies , bilateral transcranial direct current stimulation ( tDCS ) of the dorsolateral prefrontal cortex ( DLPFC ) ( anode right/cathode left ) reduces food craving and caloric intake . We design ed the present study to evaluate the neural mechanisms that underlie these effects . We replicated the design of one of these previous studies but included electroencephalographic assessment s to register evoked potentials in a Go/No-go task that contained pictures of food and furniture ( a control visual stimulus ) . We collected data from nine women ( mean age = 23.4 ± 2 years ) in a crossover experiment . We observed that active DLPFC tDCS ( anode right/cathode left ) , compared with sham stimulation , reduced the frontal N2 component and enhanced the P3a component of responses to No-go stimuli , regardless of the stimulus condition ( food or furniture ) . Active tDCS was also associated with a reduction in caloric intake . We discuss our findings in the context of cortico-subcortical processing of craving and tDCS effects on inhibitory control neural circuitry Bulimia nervosa , binge-eating disorder , and some forms of obesity are characterised by compulsive overeating that is often precipitated by food craving . Transcranial direct current stimulation ( tDCS ) has been used to suppress food cravings , but there is insufficient evidence to support its application in clinical practice . Furthermore , the potential moderating role of impulsivity has not been considered . This study used a r and omised within-subjects crossover design to examine whether a 20-minute session of sham-controlled bilateral tDCS to the dorsolateral prefrontal cortex ( anode right/cathode left ) would transiently modify food cravings and temporal discounting ( TD ; a measure of choice impulsivity ) in 17 healthy women with frequent food cravings . Whether the effects of tDCS on food craving were moderated by individual differences in TD behaviour was also explored . Participants were exposed to food and a film of people eating , and food cravings and TD were assessed before and after active and sham stimulation . Craving for sweet but not savoury foods was reduced following real tDCS . Participants that exhibited more reflective choice behaviour were more susceptible to the anti-craving effects of tDCS than those that displayed more impulsive choice behaviour . No differences were seen in TD or food consumption after real versus sham tDCS . These findings support the efficacy of tDCS in temporarily lowering food cravings and identify the moderating role of TD behaviour Study ing social behavior often requires the simultaneous interaction of many subjects . As yet , however , no painless , noninvasive brain stimulation tool existed that allowed the simultaneous affection of brain processes in many interacting subjects . Here we show that transcranial direct current stimulation ( tDCS ) can overcome these limits . We apply right prefrontal cathodal tDCS and show that subjects ' propensity to punish unfair behavior is reduced significantly BACKGROUND The dorsolateral prefrontal cortex ( DLPFC ) plays an important role in appetite and food intake regulation . OBJECTIVE Because previous data revealed that transcranial direct current stimulation ( tDCS ) of the DLPFC reduces food cravings , we hypothesized that repetitive electric stimulation of the right DLPFC would lower food intake behavior in humans . DESIGN In a single-blind , code-based , placebo-controlled , counterbalanced , r and omized crossover experiment , 14 healthy young men with body mass index ( in kg/m(2 ) ) from 20 to 25 were examined during 8 d of daily tDCS or a sham stimulation . After tDCS or sham stimulation on the first and the last day of both experimental conditions , participants consumed food ad libitum from a st and ardized test buffet . RESULTS One week of daily anodal tDCS reduced overall caloric intake by 14 % in comparison with sham stimulation . Moreover , repetitive tDCS diminished self-reported appetite scores . CONCLUSION Our study implies that the application of anodal direct currents to the right DLPFC represents a promising option for reducing both caloric intake and appetite in humans . This trial was registered at the German Clinical Trials Register ( www.germanctr.de ) as DRKS00005811 OBJECTIVE Brain polarization in the form of transcranial direct current stimulation ( tDCS ) , which influences motor function and learning processes , has been proposed as an adjuvant strategy to enhance training effects in Neurorehabilitation . Proper testing in Neurorehabilitation requires double-blind sham-controlled study design s. Here , we evaluated the effects of tDCS and sham stimulation ( SHAM ) on healthy subjects and stroke patients ' self-report measures of attention , fatigue , duration of elicited sensations and discomfort . METHODS tDCS or SHAM was in all cases applied over the motor cortex . Attention , fatigue , and discomfort were self rated by study participants using visual analog scales . Duration of perceived sensations and the ability to distinguish tDCS from Sham sessions were determined . Investigators question ing the patients were blind to the intervention type . RESULTS tDCS and SHAM elicited comparably minimal discomfort and duration of sensations in the absence of differences in attention or fatigue , and could not be distinguished from SHAM by study participants nor investigators . CONCLUSIONS Successful blinding of subjects and investigators and ease of application simultaneously with training protocol s supports the feasibility of using tDCS in double-blind , sham-controlled r and omized trials in clinical Neurorehabilitation . SIGNIFICANCE tDCS could evolve into a useful tool , in addition to TMS , to modulate cortical activity in Neurorehabilitation This study examined whether a 20-min session of prefrontal transcran Output:	So far focusing essentially on abnormal eating , these studies suggest that tDCS ( right prefrontal anode/left prefrontal cathode ) reduces food craving induced by visual stimuli . Conclusions : Despite method ological and technical differences between studies , the results are promising .
MS21385	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: STUDY DESIGN Prospect i ve 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 In a prospect i ve study of 321 consecutive cases of dislocation ankle fractures , operatively treated according to the AO ( ASIF ) principles , 306 cases ( 95 % ) were followed up two to six years after surgery . The infection rate was 1.8 % with no septic arthritis . The clinical results were " excellent and good " in 82 % , " acceptable " in 8 % , and " poor " in 10 % . Posttraumatic arthritis occurred in 14 % and was significantly more common among middle-aged women . There was a strong correlation between the degree of arthritis and the clinical result . A computer analysis ( AID ) revealed that the most decisive factors influencing the clinical result were the type of fracture , the accuracy of the reduction , and the sex of the patient . Exact reduction , rigid internal fixation , early postoperative joint exercises , and subsequent full weight-bearing in a below-the-knee walking plaster are essential for a good end result of fracture-dislocations of the ankle joint BACKGROUND AND PURPOSE Passive joint mobilization is commonly used by physical therapists as an intervention for acute ankle inversion sprains . A r and omized controlled trial with blinded assessors was conducted to investigate the effect of a specific joint mobilization , the anteroposterior glide on the talus , on increasing pain-free dorsiflexion and 3 gait variables : stride speed ( gait speed ) , step length , and single support time . SUBJECTS Forty-one subjects with acute ankle inversion sprains ( < 72 hours ) and no other injury to the lower limb entered the trial . METHODS Subjects were r and omly assigned to 1 of 2 treatment groups . The control group received a protocol of rest , ice , compression , and elevation ( RICE ) . The experimental group received the anteroposterior mobilization , using a force that avoided incurring any increase in pain , in addition to the RICE protocol . Subjects in both groups were treated every second day for a maximum of 2 weeks or until the discharge criteria were met , and all subjects were given a home program of continued RICE application . Outcomes were measured before and after each treatment . RESULTS The results showed that the experimental group required fewer treatment sessions than the control group to achieve full pain-free dorsiflexion . The experimental group had greater improvement in range of movement before and after each of the first 3 treatment sessions . The experimental group also had greater increases in stride speed during the first and third treatment sessions . DISCUSSION AND CONCLUSION Addition of a talocrural mobilization to the RICE protocol in the management of ankle inversion injuries necessitated fewer treatments to achieve pain-free dorsiflexion and to improve stride speed more than RICE alone . Improvement in step length symmetry and single support time was similar in both groups OBJECTIVE To test the efficacy of low-level laser therapy on lateral ankle sprains as an addition to a st and ardized treatment regimen , a trial was conducted in which high-dose laser ( 5J/cm2 ) , low-dose laser ( 0.5J/cm2 ) , and placebo laser therapy ( 0J/cm2 ) at skin level were compared . DESIGN R and omized , double-blind , controlled clinical trial with a follow-up of 1 year . Patients , therapists , assessors , and analysts were blinded to the assigned treatment . SETTING An ambulatory care setting . PATIENTS After informed consent and verification of exclusion criteria , 217 patients with acute lateral ankle sprains were r and omized to three groups from September 1 , 1993 , through December 31 , 1995 . INTERVENTIONS Twelve treatments of 904 nm laser therapy in 4 weeks as an adjunct to a st and ardized treatment regimen of 4 weeks of brace therapy combined with st and ardized home exercises and advice . The laser therapy device used was a 904 nm Ga-As laser , with 25-watt peak power and 5,000 or 500Hz frequency , a pulse duration of 200nsec , and an irradiated area of 1cm2 . PRIMARY OUTCOME MEASURES Pain and function as reported by the patient . RESULTS Intention-to-treat analysis of the short-term results showed no statistically significant difference on the primary outcome measure , pain ( p = .41 ) , although the placebo group showed slightly less pain . Function was significantly better in the placebo group at 10 days ( p = .01 ) and 14 days ( p = .03 ) after r and omization . The placebo group also performed significantly better on days of sick leave ( p = .02 ) and at some points for hindrance in activities in daily life and pressure pain , as well as subjective recovery ( p = .05 ) . Intention-to-treat analysis showed that total days of absenteeism from work and sports were remarkably lower in the placebo group than in the laser groups , ranging from 3.7 to 5.3 and 6 to 8 days , respectively . The total number of relapses at 1 year in the low-dose laser group ( n = 22 ) was significantly higher ( p = .04 ) than in the other two groups ( high laser , n = 13 ; placebo , n = 13 ) . Subgroup analysis to correct for possible confounders did not alter these findings . CONCLUSIONS Neither high- nor low-dose laser therapy is effective in the treatment of lateral ankle sprains BACKGROUND During the recovery period after acute ankle sprain , it is unclear whether conventional treatment should be supported by supervised exercise . AIM To evaluate the short- and long-term effectiveness of conventional treatment combined with supervised exercises compared with conventional treatment alone in patients with an acute ankle sprain . DESIGN R and omised controlled clinical trial . SETTING A total of 32 Dutch general practice s and the hospital emergency department . METHOD Adults with an acute lateral ankle sprain consulting general practice s or the hospital emergency department were allocated to either conventional treatment combined with supervised exercises or conventional treatment alone . Primary outcomes were subjective recovery ( 0 - 10 point scale ) and the occurrence of a resprain . Measurements were carried out at intake , 4 weeks , 8 weeks , 3 months , and 1 year after injury . Data were analysed using intention-to-treat analyses . RESULTS A total of 102 patients were enrolled and r and omised to either conventional treatment alone or conventional treatment combined with supervised exercise . There was no significant difference between treatment groups concerning subjective recovery or occurrence of resprains after 3 months and 1-year of follow-up . CONCLUSION Conventional treatment combined with supervised exercises compared to conventional treatment alone during the first year after an acute lateral ankle sprain does not lead to differences in the occurrence of resprains or in subjective recovery The sport and leisure industry is one of the fastest growing sectors of the business market . It has been estimated that each year 1–1.5 million people attend accident and emergency ( A&E ) departments in Britain,1 and 3.7 million people present to emergency departments in the USA,2 with an injury related to sport and exercise . With these levels of presentation A&E departments can provide valuable research into the demographics of sports related injuries . There are numerous studies regarding the incidence of sports injuries within a community or defined population , however , there is little modern research investigating specifically the nature of sports injuries presenting to an A&E department in Britain.3–6 Other studies have been published from Irel and , 7,8 Europe,9–11 Australasia,12,13 Asia,14 and more recently North America.2,15 This observational study aim ed to determine the incidence of attendance , types of injuries , nature of the sport involved , and the arrangements for follow up management in patients presenting , with an injury related to sport , to the A&E department of Crosshouse Hospital , Kilmarnock . The study took place prospect ively over a period of three months from February to April 1999 and included people 16 years of age or over . Any patient presenting with an injury attributable to participation in organised sport or recreational activity had their details and A&E number noted by the triage nurse on duty . Only new attendances were included . Relevant A&E cards Background : Lateral ligament ankle sprains are the single most common sports injury . Objective : To determine the functional outcome of the ankle joint after a moderate or severe inversion injury , comparing st and ard treatment with an elastic support b and age against an Aircast ankle brace . Design : Prospect i ve , r and omised controlled trial . Setting : Two accident and emergency departments . Method : Fifty patients presenting consecutively were r and omised into two equal groups : one group was treated with an elastic support b and age and the other with an Aircast ankle brace . All patients were given a st and ardised advice sheet referring to rest , ice , compression , and elevation . Patients were review ed after 48–72 hours , 10 days , and one month . Primary outcome measure : Ankle joint function assessed at 10 days and one month using the modified Karlsson scoring method ( maximum score 90 ) . Secondary outcome measure : The difference in ankle girth ( swelling ) and pain score at 10 days . Results : Seventeen patients in the elastic support b and age group ( six defaulted , two excluded ) and 18 patients in the Aircast ankle brace group ( six defaulted , one excluded ) completed the study . There were no significant differences between the two groups at presentation in terms of age ( mean 35.3 and 32.6 years respectively ) , sex , dominant leg , left or right ankle injured , previous injury , time to presentation ( median three and four hours respectively ) , difference in ankle girth ( mean 14.5 and 14.3 mm respectively ) , and pain scores ( mean 6.2 and 5.8 respectively ) . The Karlsson score was significantly higher in the Aircast ankle cast group than in the elastic b and age group at 10 days ( mean 50 v 35 , p = 0.028 , 95 % confidence interval ( CI ) 1.7 to 27.7 ) and one month ( mean 68 v 55 , p = 0.029 , 95 % CI 1.4 to 24.8 ) ( Student ’s t test ) . There was no difference between the groups in the secondary outcome measures ( swelling , p = 0.09 ; pain , p = 0.07 ) . When hierarchical multiple regression analysis was used to correct for possible baseline confounding factors , the Aircast ankle brace group was significantly associated with higher Karlsson scores at 10 days ( p = 0.009 ) and one month ( p = 0.024 ) . Conclusion : The use of an Aircast ankle brace for the treatment of lateral ligament ankle sprains produces a significant improvement in ankle joint function at both 10 days and one month compared with st and ard management with an elastic support b and age 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 -adjust Output:	After ankle sprain , there is evidence for the use of functional support and non-steroidal anti-inflammatory drugs . There is weak evidence suggesting that the use of manual therapy may lead to positive short-term effects . Electro-physical agents do not appear to enhance outcomes and are not recommended . Exercise may reduce the occurrence of recurrent ankle sprains and may be effective in managing chronic ankle instability . After surgical fixation for ankle fracture , an early introduction of activity , administered via early weight-bearing or exercise during the immobilization period , may lead to better outcomes . However , the use of a brace or orthosis to enable exercise during the immobilization period may also lead to a higher rate of adverse events , suggesting that this treatment regimen needs to be applied judiciously .
MS21386	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Study Design . Thromboembolic disease ( TED ) after anterior/posterior spinal reconstructions was prospect ively evaluated in 66 consecutive patients . Objective . Determine the incidence of TED after anterior/posterior spinal reconstruction . Summary of Background Data . Few studies have examined the rate of TED after potentially high-risk combined anterior/posterior reconstructions . Magnetic resonance venography ( MRV ) is more effective at detecting pelvic deep venous thrombosis ( DVT ) than conventional screening , but has not been used in these patients . Methods . We undertook a prospect i ve cohort study of 66 consecutive adult patients ( mean , 52.7 ± 9.6 years ) undergoing combined anterior/posterior spinal reconstructions for spinal deformity . All patients received only mechanical DVT prophylaxis . After surgery , MRV and bilateral lower extremity Doppler ultrasounds were obtained to screen for DVT , and contrast-enhanced spiral computed tomography scans were obtained for clinical suspicion of pulmonary embolism ( PE ) . Results . The total incidence of postoperative TED was 13.6 % ( 9 patients ) . The overall rate of DVT was 9.1 % ( 6 patients ) , one-third occurring in the pelvis . PE developed in 7.6 % ( 5 patients ) . In 2 patients , PE developed less than 48 hours after positive dopplers . In 3 patients , PE developed despite negative screening studies . Right-sided thoracoabdominal approaches were associated with an increased risk of developing DVT ( P = 0.03 , Odds Ratio 9.8 ) , PE ( P = 0.01 , Odds Ratio 20 ) , and TED ( P = 0.004 , Odds Ratio 12 ) . Conclusion . We report a high rate of TED after extensive anterior/posterior spinal reconstructions , for which a right-sided thoracoabdominal approach is an independent risk factor and screening ineffective at preventing PE . These patients should be considered at high risk for postoperative TED In a prospect i ve , r and omized , double-blind investigation of anticoagulant agents for prevention of deep vein thrombosis in patients undergoing operations at the lumbar-vertebral disc , 179 patients were r and omly allocated to two groups . 87 patients received a fixed combination of low-molecular weight heparin 1,500 U-aPTT plus dihydroergotamine 0.5 mg ( LMWH/DHE ) once a day and additionally one injection of placebo per day , 92 patients received a fixed combination of sodium heparin 5,000 U plus dihydroergotamine 0.5 mg ( HDHE ) twice a day . Treatment was initiated two hours preoperatively in both groups and continued for at least seven days . Deep vein thrombosis ( DVT ) , detected by the 125Iodine-labelled fibrinogen uptake-test , occurred in four patients treated with LMWH/DHE and in three patients with HDHE . In all seven patients phlebography was performed , confirming the diagnosis of DVT in one patient of the LMWH/DHE group and in two patients of the HDHE group , only . No increased bleeding was found in either group . Especially no neurological complications caused by epidural bleeding were observed . We therefore recommended to treat routineously all patients undergoing operations at the vertebral disc with antithrombotic agents . The advantages of the once daily regimen with low-molecular weight heparin include better patients ' acceptance and less nursing time We performed a prospect i ve study of 317 patients in order to determine the prevalence of deep venous thrombosis after reconstructive operations on the spine ; 126 of the patients were examined with duplex ultrasound assessment s of the lower extremities to ensure that no asymptomatic thrombi were being missed . Thigh-high stockings and sequential pneumatic compression of the lower extremities were used , in all patients , for prophylaxis against venous thrombosis . No antiplatelet agents or anticoagulant medications were administered . There was no evidence of thrombosis on any of the duplex ultrasound studies . Subsequently , venous thrombosis developed and was treated successfully in one of the 126 tested patients and in one of the 191 untested patients , and a fatal pulmonary embolus developed in one of the untested patients . The over-all clinical prevalence of thrombotic complications was 0.9 per cent ( three complications in 317 patients ) . All three of the patients who had clinical evidence of thrombosis had had an anterior lumbar procedure because of a degenerative disorder or trauma ; however , we could not prove that this approach or these diagnoses were significant risk factors for thrombosis ( p < 0.05 ) . While it is possible that some thrombi may have escaped both clinical and ultrasonic detection , such thrombi apparently were not enough of a danger to warrant the use of intensive prophylactic procedures that are associated with more risk . On the basis of this prospect i ve study , therefore , we think that routine screening for the detection of asymptomatic thrombosis in patients who have had a procedure on the spine is unwarranted We prospect ively studied the incidence of deep vein thrombosis ( DVT ) of the thigh in 117 patients having posterior lumbar spinal fusion with instrumentation and bone grafting for degenerative disk disease or spondylolisthesis . Patients with neoplasm , infection , trauma , or history of DVT were excluded . Patients were r and omized into two groups . In the operating room , group 1 patients were placed in thigh-high antiembolic compression stockings ( TED hose ) , and group 2 patients were placed in antiembolic stockings and pneumatic compression stockings . In both groups , the stockings were used until discharge . Postoperatively , patients in both groups received 600 mg buffered aspirin twice daily . Comparative analysis of the two groups showed no difference in operative time , blood loss , number of levels of lumbar vertebrae fused , time to mobilization , weight , age , or sex . All patients had duplex scanning of the thigh postoperatively . No patient in the series was observed to have acute DVT by clinical examination or by ultrasonography Summary We have evaluated the incidence of bleeding complications using miniheparin(2 × 2500IU daily)-dihydroergotamine starting preoperatively in a r and omized , controlled , prospect i ve , double-blind study in 50 patients undergoing herniated lumbar disc operations . There was no difference in the incidence of intraoperative bleeding problems between the two groups . Preoperatively , 13 patients have been treated in another hospital with conventional low-dose heparin , and of these 13 patients , 7 developed bleeding complications . There were two deep wound hematomas in the placebo group . Early removal of stitches or operative revision of the wound was not necessary in either group . We conclude that the use of minidose heparin-dihydroergotamine is feasible for the prevention of thromboembolic complications in patients undergoing herniated lumbar disc operations , since an increased incidence of bleeding complications was not observed . This preventive method should therefore be further clinical ly evaluated Study Design . Intermittent pneumatic compression stockings ( IPC ) alone were prospect ively used to avoid deep venous thrombosis ( DVT ) and pulmonary embolism ( PE ) in 100 consecutive patients undergoing single-level anterior corpectomy/fusion ( ACF ) and in 100 patients having multilevel ACF/posterior fusion . Objectives . To determine the optimal prophylaxis against DVT and PE for patients undergoing anterior cervical spinal surgery . Background Data . Mini-heparin and low-dose heparin prophylaxis in neurosurgery poses a 2 % to 4 % risk of major postoperative hemorrhage with result ant neurologic sequelae . Methods . Prophylaxis consisted of IPC alone . Doppler studies of the lower extremities were routinely obtained 2 days after surgery . Single-level ACF ( 100 patients ) addressed two-level disc disease , spondylostenosis , and ossification of the posterior longitudinal ligament ( OPLL ) . One hundred patients undergoing multilevel ACF ( 3 + levels ) with posterior fusion ( C2–T1 ) exhibited OPLL/spondylostenosis . Results . One patient undergoing single-level ACF developed DVT/PE 6 days after surgery ; she exhibited Factor V Leiden mutation ( hypercoagulability syndrome ) . Although 7 patients undergoing circumferential surgery developed DVT 2 to 14 days following surgery ( mean , 7.15 days ) , only two clots localized in the iliac veins result ed in PEs ( days 10 and 14 after surgery ) . Conclusions . IPCs were as effective for prophylaxis against DVT/PE for 100 patients undergoing single-level ACF and for 100 having circumferential procedures as existing therapies ( mini-heparin and low-dose heparin ) , without the risk of hemorrhage . However , the 1 % and 2 % respective rates of PE were comparable to frequencies of PE encountered in other cranial/spinal series using mini-heparin and /or low-dose heparin regimens but avoided the 2 % to 4 % risk of major postoperative hemorrhage There is a need to improve postoperative analgesia to support the trend to shorter hospitalization after minimally invasive spine surgeries . Ketorolac Tromethamine has proven efficacy in decreasing postoperative pain but there is concern with postoperative epidural bleeding after spine procedures . We prospect ively assessed the incidence of bleeding complications after microdiscectomy in patients treated with a single 30 mg intraoperative dose of Ketorolac subsequent to wound closure . Group 1 consisted of 44 patients , 24 women and 20 men with mean age of 35.7 years ( 20 to 68 y ) treated with Ketorolac . Group 2 consisted of 45 patients , 28 men and 17 women with mean age 46.8 years ( 32 to 74 y ) , who underwent discectomy without Ketorolac . Postoperative bleeding complications were monitored along with pain levels and time to discharge . We detected no significant postoperative changes in coagulation parameters or bleeding from the surgical site in either group . Both group 1 and 2 had averaged preoperative visual analog scale scores for leg pain of 8 . Group 1 had an average postoperative visual analog scale score of 2.6 compared with 4 for group 2 two hours after surgery . Single dose intravenous Ketorolac provided beneficial analgesia without significant increase in risk of bleeding after microdiscectomy , enabling us to consistently perform microdiscectomy as an ambulatory procedure . Meticulous hemostasis should be accomplished before closure . Prolonged postoperative use is a promising alternative to narcotics STUDY DESIGN Adult spinal surgery patients were studied prospect ively to determine the incidence of sub clinical deep venous thrombosis . An overlapping group of patients was review ed retrospectively for symptomatic thromboembolism . OBJECTIVES To determine the incidence of symptomatic and asymptomatic thromboembolism in spinal surgery patients . SUMMARY OF BACKGROUND DATA Although thromboembolic complications are known to occur after spinal operations , there are limited published data on the incidence of pulmonary embolus or deep venous thrombosis after major spinal surgery . METHODS One hundred sixteen adult spinal surgery patients were examined with duplex ultrasound to determine the incidence of deep venous thrombosis . Seventy-three of these patients also underwent lung perfusion scans to look for sub clinical pulmonary embolism . A retrospective review was conducted of symptomatic thromboembolic complications occurring in a 2-year period at the authors ' center . Three hundred and eighteen major spinal reconstructive procedures were performed during the period review ed , which included the period of the prospect i ve study and therefore the patients of the prospect i ve group . Thigh-length compression stockings and pneumatic compression leggings were used for prophylaxis in all patients . RESULTS One patient had an asymptomatic iliac vein thrombosis , and seven patients had symptomatic pulmonary embolism ( 2.2 % ) . Six of the symptomatic pulmonary emboli occurred after combined anterior/posterior spinal fusions ( 6 % ) , whereas only one occurred after posterior decompression and fusion ( 0.5 % ) . CONCLUSIONS Duplex ultrasound appeared insensitive for diagnosing clots before embolization in this patient group . Simple mechanical prophylaxis for thromboembolism , which may be adequate for patients undergoing posterior procedures , may not be as protective for patients undergoing combined anterior/posterior spine surgery Study Design . A prospect i ve clinical study using venography to evaluate deep venous thrombosis after posterior spinal surgery . Objectives . To demonstrate the prevalence of deep venous thrombosis after posterior spinal surgery with no prophylaxis . Summary of Background Data . There have been few studies about the occurrence of deep venous thrombosis after spinal surgery in which venography was used for screening . Methods . Of the enrolled 134 patients undergoing posterior spinal surgery , 110 ( 82.1 % ) were examined with complete surveillance for deep venous thrombosis by venography . There were 64 males and 46 females . The average age at operation was 59.0 years ( range , 14–86 years ) . The levels of the operation were cervical in 54 , thoracic in 7 , and lumbar in 49 . All procedures were performed with patients under general anesthesia . Neither mechanical methods nor anticoagulation medications were used Output:	Fatal pulmonary embolism was rare . CONCLUSION Venous thromboembolism is uncommon after elective spine surgery . Trauma patients are at increased risk , and chemical prophylaxis should be considered .
MS21387	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: 33 patients with refractory irritable bowel syndrome were treated with four 40-minute sessions of hypnotherapy over 7 weeks . 20 improved , 11 of whom lost almost all their symptoms . Short-term improvement was maintained for 3 months without further formal treatment . Hypnotherapy in groups of up to 8 patients was as effective as individual therapy OBJECTIVES : Irritable bowel syndrome is the most common gastrointestinal diagnosis . The symptoms of irritable bowel syndrome are similar to those of small intestinal bacterial overgrowth . The purpose of this study was to test whether overgrowth is associated with irritable bowel syndrome and whether treatment of overgrowth reduces their intestinal complaints . METHODS : Two hundred two subjects in a prospect i ve data base of subjects referred from the community undergoing a lactulose hydrogen breath test for assessment of overgrowth were Rome I criteria positive for irritable bowel syndrome . They were treated with open label antibiotics after positive breath test . Subjects returning for follow-up breath test to confirm eradication of overgrowth were also assessed . Subjects with inflammatory bowel disease , abdominal surgery , or subjects demonstrating rapid transit were excluded . Baseline and after treatment symptoms were rated on visual analog scales for bloating , diarrhea , abdominal pain , defecation relief , mucous , sensation of incomplete evacuation , straining , and urgency . Subjects were blinded to their breath test results until completion of the question naire . RESULTS : Of 202 irritable bowel syndrome patients , 157 ( 78 % ) had overgrowth . Of these , 47 had follow-up testing . Twenty-five of 47 follow-up subjects had eradication of small intestinal bacterial overgrowth . Comparison of those that eradicated to those that failed to eradicate revealed an improvement in irritable bowel syndrome symptoms with diarrhea and abdominal pain being statistically significant after Bonferroni correction ( p < 0.05 ) . Furthermore , 48 % of eradicated subjects no longer met Rome criteria ( χ2= 12.0 , p < 0.001 ) . No difference was seen if eradication was not successful . CONCLUSIONS : Small intestinal bacterial overgrowth is associated with irritable bowel syndrome . Eradication of the overgrowth eliminates irritable bowel syndrome by study criteria in 48 % of subjects BACKGROUND The cause of irritable bowel syndrome ( IBS ) is unknown . It may follow gastroenteritis and be associated with an abnormal gut flora and with food intolerance . Our study was design ed to assess whether these factors were associated with colonic malfermentation . METHODS We carried out a crossover controlled trial of a st and ard diet and an exclusion diet matched for macronutrients in six female IBS patients and six female controls . During the final 72 h on each diet , faecal excretion of fat , nitrogen , starch , and non-starch polysaccharide NSP was measured , and total excretion of hydrogen and methane collected over 24 h in a purpose -built 1.4 m3 whole-body calorimeter . Breath hydrogen and methane excretion were then measured for 3 h after 20 g oral lactulose . FINDINGS The maximum rate of gas excretion was significantly greater in patients than in controls ( 2.4 mL/min IQR 1.7 - 2.6 vs 0.6 , 0.4 - 1.1 ) . Although total gas production in patients was not greater than in controls ( median 527 mL/24 h IQR 387 - 660 vs 412 , 234 - 507 ) , hydrogen production was higher ( 332 , 318 - 478 vs 162 , 126 - 217 , p=0.009 ) . In patients , the exclusion diet reduced symptoms and produced a fall in maximum gas excretion ( 0.5 mL/min IQR 0.3 - 0.7 ) . After lactulose , breath hydrogen was greater on the st and ard than on the exclusion diet . INTERPRETATION Colonic-gas production , particularly of hydrogen , is greater in patients with IBS than in controls , and both symptoms and gas production are reduced by an exclusion diet . This reduction may be associated with alterations in the activity of hydrogen-consuming bacteria . Fermentation may be an important factor in the pathogenesis of IBS CONTEXT Irritable bowel syndrome ( IBS ) is a common functional bowel disorder for which there is no reliable medical treatment . OBJECTIVE To determine whether Chinese herbal medicine ( CHM ) is of any benefit in the treatment of IBS . DESIGN R and omized , double-blind , placebo-controlled trial conducted during 1996 through 1997 . SETTING Patients were recruited through 2 teaching hospitals and 5 private practice s of gastroenterologists , and received CHM in 3 Chinese herbal clinics . PATIENTS A total of 116 patients who fulfilled the Rome criteria , an established st and ard for diagnosis of IBS . INTERVENTION Patients were r and omly allocated to 1 of 3 treatment groups : individualized Chinese herbal formulations ( n = 38 ) , a st and ard Chinese herbal formulation ( n = 43 ) , or placebo ( n = 35 ) . Patients received 5 capsules 3 times daily for 16 weeks and were evaluated regularly by a traditional Chinese herbalist and by a gastroenterologist . Patients , gastroenterologists , and herbalists were all blinded to treatment group . MAIN OUTCOME MEASURES Change in total bowel symptom scale scores and global improvement assessed by patients and gastroenterologists and change in the degree of interference in life caused by IBS symptoms assessed by patients . RESULTS Compared with patients in the placebo group , patients in the active treatment groups ( st and ard and individualized CHM ) had significant improvement in bowel symptom scores as rated by patients ( P=.03 ) and by gastroenterologists ( P=.001 ) , and significant global improvement as rated by patients ( P=.007 ) and by gastroenterologists ( P=.002 ) . Patients reported that treatment significantly reduced the degree of interference with life caused by IBS symptoms ( P=.03 ) . Chinese herbal formulations individually tailored to the patient proved no more effective than st and ard CHM treatment . On follow-up 14 weeks after completion of treatment , only the individualized CHM treatment group maintained improvement . CONCLUSION Chinese herbal formulations appear to offer improvement in symptoms for some patients with IBS Twenty patients with irritable bowel syndrome ( IBS ) were r and omly assigned either to intensive , individualized cognitive therapy ( 10 sessions over 8 weeks ) or to 8 weeks of daily gastrointestinal ( GI ) symptom monitoring . Pre- to posttreatment evaluations showed significantly ( p = .005 ) greater GI symptom reduction for those receiving cognitive therapy than for those in symptom monitoring . At posttreatment , 80 % of the cognitive therapy group showed clinical ly significant improvement , whereas only 10 % of the monitoring group showed this . Results held up well at a 3-month follow-up . Within the cognitive therapy group , GI symptom reductions correlated significantly with increases in positive and reductions in negative automatic thoughts The aim of this study was to evaluate the effect of a novel laxative preparation , composed of cel and in , aloevera and psyllium in patients with chronic constipation . Thirty-five men and women were r and omized to receive capsules containing cel and in-aloevera-psyllium , or placebo , in a double-blind trial lasting 28 days . Symptoms in the last 2 weeks of the treatment period were compared to those in the 14-day pre-trial basal period . In the cel and in , aloevera and psyllium group , bowel movements became more frequent , the stools were softer and laxative dependence was reduced . In the placebo group , all these parameters were unchanged . Abdominal pain was not reduced in either group . The results of this study show that the preparation is an effective laxative in the treatment of constipation 30 patients with severe refractory irritable-bowel syndrome were r and omly allocated to treatment with either hypnotherapy or psychotherapy and placebo . The psychotherapy patients showed a small but significant improvement in abdominal pain , abdominal distension , and general well-being but not in bowel habit . The hypnotherapy patients showed a dramatic improvement in all features , the difference between the two groups being highly significant . In the hypnotherapy group no relapses were recorded during the 3-month follow-up period , and no substitution symptoms were observed A double-blind crossover trial of oligofructose ( Raftilose P95 ) 2 g three times daily against sucrose ( 1 g ) three times daily was performed in patients suffering from irritable bowel syndrome . Each treatment was followed for 4 wk . Patients consumed a st and ardized diet during the last 14 d of each treatment period , and symptoms were assessed using a previously vali date d question naire . Fecal weight and pH , whole-gut transit time and fasting breath hydrogen concentrations were measured at the start of the study and at the end of each treatment period . Oligofructose produced no significant change in any of these parameters even when patients were divided into those with predominant diarrhea ( n = 14 ) and those with predominant constipation ( n = 7 ) . Oligofructose at a dose of 6 g/d had no therapeutic value in patients with irritable bowel syndrome 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 In a double-blind , crossover study , wedetermined whether microencapusulated pancreatic enzymesreduce postpr and ial symptoms experienced by healthyvolunteers after ingestion of a high calorie , high fat meal . At 7 AM , 18 subjects ingested 185 g ofcookies ( 1196 calories and 72 g of fat ) with threepancrelipase capsules or a placebo . The severity ofgastrointestinal symptoms and flatus passages wererecorded for 15 - 17 hr , and end-alveolar sample s wereobtained hourly for 10 hr . Ingestion of pancreaticsupplements was associated with a significant ( P = 0.049 ) reduction in bloating over the entire recordingperiod , and with significant reductions in bloating , gas , and fullness during the dinner to bedtime period . Pancreatic supplements had no significant effect onbreath H2 or CH4 concentration . The finding that pancreatic supplements reduce postpr and ial symptoms inhealthy subjects suggests that these supplements alsomight be beneficial in irritable bowelsyndrome Previous research from the United Kingdom has shown hypnotherapy to be effective in the treatment of irritable bowel syndrome ( IBS ) . The current study provides a systematic replication of this work in the United States . Six matched pairs of IBS patients were r and omly assigned to either a gut-directed hypnotherapy ( n=6 ) or to a symptom monitoring wait-list control condition ( n=6 ) in a multiple baseline across subjects design . Those assigned to the control condition were later crossed over to the treatment condition . Subjects were matched on concurrent psychiatric diagnoses , susceptibility to hypnosis , and various demographic features . On a composite measure of primary IBS symptoms , treatment was superior ( p=.016 ) to symptom monitoring . Results from the entire treated sample ( n=11 ; one subject was removed from analysis ) indicate that the individual symptoms of abdominal pain , constipation , and flatulence improved significantly . State and trait anxiety scores were also seen to decrease significantly . Results at the 2-month follow-up point indicated good maintenance of treatment gains . No significant correlation was found between initial susceptibility to hypnosis and treatment gain . A positive relationship was found between the incidence of psychiatric diagnosis and overall level of improvement The effectiveness of ginger ( Zingiber officinale ) as an antiemetic agent was compared with placebo and metoclopramide in 60 women who had major gynaecological surgery in a double‐blind , r and omised study . There were statistically significantly fewer recorded incidences of nausea in the group that received ginger root compared with placebo ( p < 0.05 ) . The number of incidences of nausea in the groups that received either ginger root or metoclopramide were similar . The administration of antiemetic after operation was significantly greater in the placebo group compared to the other two groups ( p < 0.05 ) BACKGROUND Symptoms of at least a subgroup of patients with irritable bowel syndrome may be associated with an alteration in gut flora . Studies on bacterial based therapy have yielded mixed results . AIMS To determine if oral administration of the probiotic Lactobacillus casei strain GG under r and omized placebo controlled conditions improves symptoms in irritable bowel syndrome patients with bloating related symptoms . PATIENTS A total of 25 patients with clinical ly confirmed irritable bowel syndrome ( Rome criteria ) were enrolled in the study . METHODS This was a r and omised double-blind placebo-controlled crossover Output:	Oral cromolyn sodium may be useful in chronic unexplained diarrhea and appears as effective as and safer than elimination diets . Alterations of enteric flora may play a role in irritable bowel syndrome , but supporting evidence for bacterial overgrowth or probiotic therapy is lacking
MS21388	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background : A better underst and ing of factors that affect breast density , one of the strongest breast cancer risk indicators , may provide important clues about breast cancer etiology and prevention . This study evaluates the association of vitamin D and calcium , from food and /or supplements , to breast density in premenopausal and postmenopausal women separately . Methods : A total of 777 premenopausal and 783 post-menopausal women recruited at two radiology clinics in Quebec City , Canada , in 2001 to 2002 , completed a food frequency question naire to assess vitamin D and calcium . Breast density from screening mammograms was assessed using a computer-assisted method . Associations between vitamin D or calcium and breast density were evaluated using linear regression models . Adjusted means in breast density were assessed according to the combined daily intakes of the two nutrients using generalized linear models . Results : In premenopausal women , total intakes of vitamin D and calcium were inversely related to breast density ( β = −1.4 ; P = 0.004 for vitamin D ; β = −0.8 ; P = 0.0004 for calcium ) . In multivariate linear regression , simultaneous increments in daily total intakes of 400 IU vitamin D and 1,000 mg calcium were associated with an 8.5 % ( 95 % confidence interval , 1.8 - 15.1 ) lower mean breast density . The negative association between dietary vitamin D intake and breast density tended to be stronger at higher levels of calcium intake and vice versa . Among postmenopausal women , intakes of vitamin D and calcium were not associated with breast density . Conclusion : These findings show that higher intakes of vitamin D and calcium from food and supplements are related to lower levels of breast density among premenopausal women . They suggest that increasing intakes of vitamin D and calcium may represent a safe and inexpensive strategy for breast cancer prevention BACKGROUND Whether a change over time in clinical ly measured mammographic breast density influences breast cancer risk is unknown . METHODS From January 1993 to December 2003 , data that included American College of Radiology Breast Imaging Reporting and Data System ( BI-RADS ) breast density categories ( 1 - 4 in order of increasing density ) were collected prospect ively on 301,955 women aged 30 and older who were not using postmenopausal hormone replacement therapy and underwent at least two screening mammography examinations ; 2639 of the women were diagnosed with breast cancer within 1 year of the last examination . Women 's first and last BI-RADS breast density ( average 3.2 years apart ) and logistic regression were used to model the odds of having invasive breast cancer or ductal carcinoma in situ diagnosed within 12 months of the last examination by change in BI-RADS category . Rates of breast cancer adjusted for age , mammography registry , and time between screening examinations were estimated from this model . All statistical tests were two-sided . RESULTS The rate ( breast cancers per 1000 women ) of breast cancer was higher if BI-RADS breast density category increased from 1 to 2 ( 5.6 , 95 % confidence interval [ CI ] = 4.7 to 6.9 ) or 1 to 3 ( 9.9 , 95 % CI = 6.4 to 15.5 ) compared to when it remained at BI-RADS density of 1 ( 3.0 , 95 % CI = 2.3 to 3.9 ; P<.001 for trend ) . Similar and statistically significant trends between increased or decreased density and increased or decreased risk of breast cancer , respectively , were observed for women whose breast density category was initially 2 or 3 and changed categories . BI-RADS density of 4 on the first examination was associated with a high rate of breast cancer ( range 9.1 - 13.4 ) that remained high even if breast density decreased . CONCLUSION An increase in BI-RADS breast density category within 3 years may be associated with an increase in breast cancer risk and a decrease in density category with a decrease in risk compared to breast cancer risk in women in whom breast density category remains unchanged . Two longitudinal measures of BI-RADS breast density may better predict a woman 's risk of breast cancer than a single measure BACKGROUND Mammographic breast density is a strong risk factor for breast cancer . Tamoxifen , which reduces the risk of breast cancer in women at high risk , also reduces mammographic breast density . However , it is not known if tamoxifen-induced reductions in breast density can be used to identify women who will benefit the most from prophylactic treatment with this drug . METHODS We conducted a nested case-control study within the first International Breast Cancer Intervention Study , a r and omized prevention trial of tamoxifen vs placebo . Mammographic breast density was assessed visually and expressed as a percentage of the total breast area in 5 % increments . Case subjects were 123 women diagnosed with breast cancer at or after their first follow-up mammogram , which took place 12 - 18 months after trial entry , and control subjects were 942 women without breast cancer . Multivariable logistic regression was used to adjust for other risk factors . All statistical tests were two-sided . RESULTS In the tamoxifen arm , 46 % of women had a 10 % or greater reduction in breast density at their 12- to 18-month mammogram . Compared with all women in the placebo group , women in the tamoxifen group who experienced a 10 % or greater reduction in breast density had 63 % reduction in breast cancer risk ( odds ratio = 0.37 , 95 % confidence interval = 0.20 to 0.69 , P = .002 ) , whereas those who took tamoxifen but experienced less than a 10 % reduction in breast density had no risk reduction ( odds ratio = 1.13 , 95 % confidence interval = 0.72 to 1.77 , P = .60 ) . In the placebo arm , there was no statistically significant difference in breast cancer risk between subjects who experienced less than a 10 % reduction in mammographic density and subjects who experienced a greater reduction . CONCLUSION The 12- to 18-month change in mammographic breast density is an excellent predictor of response to tamoxifen in the preventive setting Background : Mammographic density is a risk factor for breast cancer . Mammographic density and breast magnetic resonance imaging ( MRI ) volume ( MRIV ) assess the amount of fibrogl and ular tissue in the breast . Mammographic density and MRIV can be modulated with hormonal interventions , suggesting that these imaging modalities may be useful as surrogate endpoint biomarkers for breast cancer chemoprevention trials . We evaluated the effect of raloxifene on mammographic density and MRIV in premenopausal women at increased risk for breast cancer . Methods : Mammograms and MRI were obtained at baseline and after 1 and 2 years of 60 mg raloxifene by mouth daily for 27 premenopausal women . Mammographic percent dense area was calculated using a semiquantitative thresholding technique . T1-weighted spoiled gradient-echo MRI with fat suppression was used to determine breast MRIV using a semiautomatic method . Mean change in mammographic density and median change in MRIV were assessed by the Wilcoxon signed-rank test . Results : No significant change in mammographic density was seen after treatment with raloxifene . Mean change after 1 year was 1 % [ 95 % confidence interval ( 95 % CI ) , −3 to + 5 ] and after 2 years was 1 % ( 95 % CI , −2 to + 5 ) . MRIV decreased on raloxifene . Median relative change in MRIV after 1 year was -17 % ( 95 % CI , -28 to -9 ; P = 0.0017 ) and after 2 years was -16 % ( 95 % CI , -31 to -4 ; P = 0.0004 ) . Conclusions : In high-risk premenopausal women , mammographic density did not change on raloxifene , whereas MRIV significantly declined . Our findings suggest that MRIV is a promising surrogate biomarker in premenopausal women at increased risk for breast cancer and should be investigated further in breast cancer prevention trials . ( Cancer Epidemiol Biomarkers Prev 2008;17(7):1696–701 Background : Calcium and vitamin D may be inversely related to breast cancer risk , in part by affecting mammographic density . However , results from previous , mostly cross-sectional studies have been mixed , and there have been few r and omized clinical trials of the effect of calcium and vitamin D supplementation on change in mammographic density . Methods : We assessed the effect of one year of supplementation on mammographic density in 330 postmenopausal women enrolled in the Women 's Health Initiative hormone therapy ( HT ) and calcium and vitamin D ( CaD ) trials . Women were r and omized to receive 1,000 mg/d of elemental calcium carbonate plus 400 IU/d of vitamin D3 or placebo . Results : After approximately one year , mammographic density decreased 2 % in the CaD supplementation group and increased 1 % in the placebo group ( ratio of means = 0.97 ; 95 % CI = 0.81–1.17 ) . Results suggested potential interaction by HT use ( P = 0.08 ) . Among women r and omized to HT placebo , the ratio of mean density comparing CaD supplementation and placebo groups was 0.82 ( 95 % CI = 0.61–1.11 ) vs. 1.16 ( 95 % CI = 0.92–1.45 ) in women r and omized to active HT . In sensitivity analyses limited to women taking ≥80 % of study supplements , ratios were 0.67 ( 95 % CI = 0.41–1.07 ) in women not assigned to HT and 1.07 ( 95 % CI = 0.79–1.47 ) women assigned to HT . Conclusions : We observed no overall effect of vitamin D and calcium supplementation on mammographic density after one year . Impact : Potential interaction between these nutrients and estrogen as related to mammographic density warrants further study . Cancer Epidemiol Biomarkers Prev ; 21(3 ) ; 462–73 . © 2012 AACR Mammographically detected breast density has been correlated with breast cancer risk . Breast density appears to be influenced by hormonal factors including increasing age , postmenopausal status , number of pregnancies , lower body weight , hormone replacement therapy , and tamoxifen therapy . The aromatase inhibitor letrozole profoundly reduces breast and circulating estrogen levels in postmenopausal women . We hypothesize that letrozole may reduce breast density and report here on its effects on mammographic breast density , bone mineral density ( BMD ) , bone biomarkers , plasma hormone , and serum lipid levels . MAP1 was a multicenter , r and omized , double-blind , placebo-controlled , feasibility trial in which postmenopausal women with or without prior invasive breast cancer were r and omized in a 2:1 ratio of letrozole ( 2.5 mg daily ) or placebo for 12 months and followed for a total of 24 months . Eligible women had an estimated > 25 % breast density on baseline mammogram . The primary endpoint was change in percent breast density ( PD ) between the baseline and 12-month mammograms as estimated by a computer-assisted thresholding program . Baseline and 12-month mammographic density was also assessed in a blinded manner by visual inspection . Secondary endpoints included changes in serum hormones , plasma lipid levels , bone biomarkers , and BMD . Data are available for 67 women ( 44 on letrozole and 23 on placebo ) . No significant changes in PD were noted between the treatment arms at either 12 or 24 months . No distinguishable difference in density measurements by visual inspection were noted between baseline and 12-month mammograms . A significant decrease in percentage change in T-score of the femoral neck at 12 months was noted in the letrozole arm without other significant changes in BMD parameters . Lipid values did not differ between treatment groups except for a borderline significant decrease in total cholesterol at 3 months among women treated with letrozole . Letrozole therapy was associated with a significant reduction in mean serum estradiol , estrone , and estrone sulfate levels at 12 months , but not at 24 months . A significant increase in serum IGF-1 levels was also noted in the letrozole group compared to the placebo group at both 12 and 24 months . To conclude , compared with placebo , 12 months of letrozole therapy does not appear to have a significant effect on mammographic PD . Twelve months of letrozole was associated with a decrease of uncertain clinical significance in the T-score of the femoral neck at 12 months which was reversible at 24 months with recovery of estrogen levels . Letrozole therapy was found to increase IGF-1 levels at 12 and 24 months Soy consumption may be related to lower breast cancer risk as assessed by breast density . The aims of this 2-y trial were to examine the effects of soy foods and lifetime soy intake on mammographic density . After 220 premenopausal women were r and omly assigned to the intervention or control group , the former group consumed 2 daily servings of soy foods equivalent to 50 mg of isoflavones and the latter consumed their regular diet . The respective dropout rates were 15.6 and 12.6 % ; adherence to the study regimen was high . We assessed lifetime soy intake with a question naire and measured breast density Output:	TAM induces BD reduction ; however , the effect of RLX , tibolone , and AIs on BD is unclear . Although data on association between diet and BD in adulthood are contradictory , intake of vegetables , vitamin D , and calcium appear to be associated with lower BD in premenopausal women
MS21389	*TASK* the task is to summarize an input biomedical literature in six sentences *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 objective was to assess the safety and efficacy of L-NMMA in the treatment of cardiogenic shock . METHODS We enrolled 11 consecutive patients with cardiogenic shock that persisted after > 24 hours from admission , despite coronary catheterization and primary percutaneous transluminal coronary revascularization , when feasible , and treatment with mechanical ventilation , intraaortic balloon pump ( IABP ) , and high doses of catecholamines . L-NMMA was administered as an IV bolus of 1 mg/kg and continuous drip of 1 mg . kg(-1 ) . h(-1 ) for 5 hours . Treatment with catecholamines , mechanical ventilation , and IABP was kept constant throughout the study . RESULTS Within 10 minutes of L-NMMA administration , mean arterial blood pressure ( MAP ) increased from 76+/-9 to 109+/-22 mm Hg ( + 43 % ) . Urine output increased within 5 hours from 63+/-25 to 156+/-63 cc/h ( + 148 % ) . Cardiac index decreased during the steep increase in MAP from 2 . 0+/-0.5 to 1.7+/-0.4 L/(min . m(2 ) ) ( -15 % ) ; however , it gradually increased to 1.85+/-0.4 L/(min . m(2 ) ) after 5 hours . The heart rate and the wedge pressure remained stable . Twenty-four hours after L-NMMA discontinuation , MAP ( + 36 % ) and urine output ( + 189 % ) remained increased ; however , cardiac index returned to pretreatment level . No adverse events were detected . Ten out of eleven patients could be weaned off mechanical ventilation and IABP . Eight patients were discharged from the coronary intensive care unit , and seven ( 64 % ) were alive at 1-month follow-up . CONCLUSIONS L-NMMA administration in patients with cardiogenic shock is safe and has favorable clinical and hemodynamic effects Background —Few data are available on the impact of heart failure ( HF ) across all types of acute coronary syndromes ( ACS ) . Methods and Results —The Global Registry of Acute Coronary Events ( GRACE ) is a prospect i ve study of patients hospitalized with ACS . Data from 16 166 patients were analyzed : 13 707 patients without prior HF or cardiogenic shock at presentation were identified . Of these , 1778 ( 13 % ) had an admission diagnosis of HF ( Killip class II or III ) . HF on admission was associated with a marked increase in mortality rates during hospitalization ( 12.0 % versus 2.9 % [ with versus without HF ] , P < 0.0001 ) and at 6 months after discharge ( 8.5 % versus 2.8 % , P < 0.0001 ) . Of note , HF increased mortality rates in patients with unstable angina ( defined as ACS with normal biochemical markers of necrosis ; mortality rates : 6.7 % with versus 1.6 % without HF at admission , P < 0.0001 ) . By logistic regression analysis , admission HF was an independent predictor of hospital death ( odds ratio , 2.2 ; P < 0.0001 ) . Admission HF was associated with longer hospital stay and higher readmission rates . Patients with HF had lower rates of catheterization and percutaneous cardiac intervention , and fewer received & bgr;-blockers and statins . Hospital development of HF ( versus HF on presentation ) was associated with an even higher in-hospital mortality rate ( 17.8 % versus 12.0 % , P < 0.0001 ) . In patients with HF , in-hospital revascularization was associated with lower 6-month death rates ( 14.0 % versus 23.7 % , P < 0.0001 ; adjusted hazard ratio , 0.5 ; 95 % CI , 0.37 to 0.68 , P < 0.0001 ) . Conclusions —In this observational registry , heart failure was associated with reduced hospital and 6-month survival across all ACS subsets , including patients with normal markers of necrosis . More aggressive treatment of these patients may be warranted to improve prognosis BACKGROUND Traditional and largely qualitative review s of evidence are now giving way to much more structured systematic overviews that use a quantitative method to calculate the overall effect of treatment . The latter approach is dependent on the quality of primary studies , which may introduce bias if they are of poor method ologic quality . OBJECTIVE To test the hypothesis that the inclusion of poor- quality trials in meta-analyses would bias the conclusions and produce incorrect estimates of treatment effect . METHODS An overview of r and omized trials of antiestrogen therapy in subfertile men with oligospermia was performed to test the hypothesis . Data sources included online search ing of MEDLINE and Science Citation Index data bases between 1966 and 1994 , scanning the bibliography of known primary studies and review articles , and contacting experts in the field . After independent , blind assessment , nine of 149 originally identified studies met the inclusion criteria and were selected . We assessed study quality independently . Outcome data from each study were pooled and statistically summarized . RESULTS There was a marginal improvement in pregnancy rate with antiestrogen treatment ( odds ratio , 1.6 ; 95 % confidence interval , 0.9 to 2.6 ) . Sensitivity analyses on the basis of method ologic quality demonstrated that poor- quality studies produced a positive effect with treatment , whereas no benefit was observed with high- quality studies . CONCLUSION The results of a meta- analysis are influenced by the quality of the primary studies included . Method ologically , poor studies tend to exaggerate the overall estimate of treatment effect and may lead to incorrect inferences The results of this study showed an advantage of nesiritide compared with high-dose nitroglycerin in the treatment of patients with decompensated heart failure . Nesiritide result ed in an early decrease in pulmonary capillary wedge pressure ( < or = 15 minutes ) , which was sustained throughout the study period ( 24 hours ) without the need for up-titration . In contrast , the onset of the nitroglycerin-mediated hemodynamic effect was delayed , and despite aggressive up-titration , the decrease in pulmonary capillary wedge pressure was gradually attenuated because of the early development of tolerance BACKGROUND To compare the safety and efficacy of nesiritide versus intravenous nitroglycerin ( NTG ) in patients with acute coronary syndromes enrolled in the Vasodilation in the Management of Acute Congestive heart failure trial . Methods and results Retrospective review of Vasodilation in the Management of Acute Congestive heart failure trial data for heart failure associated with prospect ively diagnosed acute coronary syndromes . Sixty-one patients were included ; 34 received nesiritide and 27 received NTG . Pulmonary capillary wedge pressure was measured in right heart-catheterized patients ( 11 nesiritide , 9 NTG ) . Death at 6 months occurred in 2 nesiritide and 5 NTG patients ( P>.2 ) . Hypotension occurred in 4 nesiritide and 3 NTG patients ( P>.6 ) . At 24 hours , pulmonary capillary wedge pressure improvements persisted ( P=.001 ) in the nesiritide group , whereas the NTG group had returned to baseline ( P>.1 ) . In non-right heart-catheterized patients , 24-hour dyspnea scores were at least moderately improved in all nesiritide and 71 % of NTG ( P=.031 ) . At least minimal dyspnea improvement was seen in 100 % of nesiritide versus 71 % of NTG patients ( P>.3 ) , and 6-hour global clinical scores were at least moderately better in 75 % of nesiritide versus 32 % of NTG ( P=.031 ) . In non-right heart-catheterized patients , there were no 30-day readmissions with nesiritide versus 17 % with NTG ( P>.2 ) . CONCLUSIONS Nesiritide is as safe as NTG in heart failure patients with acute coronary syndromes BACKGROUND The leading cause of death in patients hospitalized for acute myocardial infa rct ion is cardiogenic shock . We conducted a r and omized trial to evaluate early revascularization in patients with cardiogenic shock . METHODS Patients with shock due to left ventricular failure complicating myocardial infa rct ion were r and omly assigned to emergency revascularization ( 152 patients ) or initial medical stabilization ( 150 patients ) . Revascularization was accomplished by either coronary-artery bypass grafting or angioplasty . Intraaortic balloon counterpulsation was performed in 86 percent of the patients in both groups . The primary end point was mortality from all causes at 30 days . Six-month survival was a secondary end point . RESULTS The mean age of the patients was 66+/-10 years , 32 percent were women and 55 percent were transferred from other hospitals . The median time to the onset of shock was 5.6 hours after infa rct ion , and most infa rcts were anterior in location . Ninety-seven percent of the patients assigned to revascularization underwent early coronary angiography , and 87 percent underwent revascularization ; only 2.7 percent of the patients assigned to medical therapy crossed over to early revascularization without clinical indication . Overall mortality at 30 days did not differ significantly between the revascularization and medical-therapy groups ( 46.7 percent and 56.0 percent , respectively ; difference , -9.3 percent ; 95 percent confidence interval for the difference , -20.5 to 1.9 percent ; P=0.11 ) . Six-month mortality was lower in the revascularization group than in the medical-therapy group ( 50.3 percent vs. 63.1 percent , P=0.027 ) . CONCLUSIONS In patients with cardiogenic shock , emergency revascularization did not significantly reduce overall mortality at 30 days . However , after six months there was a significant survival benefit . Early revascularization should be strongly considered for patients with acute myocardial infa rct ion complicated by cardiogenic shock OBJECTIVE To determine the feasibility , safety and efficacy of bilevel positive airway ventilation ( BiPAP ) in the treatment of severe pulmonary edema compared to high dose nitrate therapy . BACKGROUND Although noninvasive ventilation is increasingly used in the treatment of pulmonary edema , its efficacy has not been compared prospect ively with newer treatment modalities . METHODS We enrolled 40 consecutive patients with severe pulmonary edema ( oxygen saturation < 90 % on room air prior to treatment ) . All patients received oxygen at a rate of 10 liter/min , intravenous ( IV ) furosemide 80 mg and IV morphine 3 mg . Thereafter patients were r and omly allocated to receive 1 ) repeated boluses of IV isosorbide-dinitrate ( ISDN ) 4 mg every 4 min ( n = 20 ) , and 2 ) BiPAP ventilation and st and ard dose nitrate therapy ( n = 20 ) . Treatment was administered until oxygen saturation increased above 96 % or systolic blood pressure decreased to below 110 mm Hg or by more than 30 % . Patients whose conditions deteriorated despite therapy were intubated and mechanically ventilated . All treatment was delivered by mobile intensive care units prior to hospital arrival . RESULTS Patients treated by BiPAP had significantly more adverse events . Two BiPAP treated patients died versus zero in the high dose ISDN group . Sixteen BiPAP treated patients ( 80 % ) required intubation and mechanical ventilation compared to four ( 20 % ) in the high dose ISDN group ( p = 0.0004 ) . Myocardial infa rct ion ( MI ) occurred in 11 ( 55 % ) and 2 ( 10 % ) patients , respectively ( p = 0.006 ) . The combined primary end point ( death , mechanical ventilation or MI ) was observed in 17 ( 85 % ) versus 5 ( 25 % ) patients , respectively ( p = 0.0003 ) . After 1 h of treatment , oxygen saturation increased to 96 + /- 4 % in the high dose ISDN group as compared to 89 + /- 7 % in the BiPAP group ( p = 0.017 ) . Due to the significant deterioration observed in patients enrolled in the BiPAP arm , the study was prematurely terminated by the safety committee . CONCLUSIONS High dose ISDN is safer and better than BiPAP ventilation combined with conventional therapy in patients with severe pulmonary edema The immediate haemodynamic effects of intravenous frusemide ( 1 mg/kg ) and intravenous isosorbide dinitrate ( 50 - 200 micrograms/kg/h ) were compared in a prospect i ve , r and omised , between-group study in 28 men with radiographic and haemodynamic evidence of left ventricular failure following acute myocardial infa rct ion . The diuresis induced by frusemide reduced the left heart filling pressure and cardiac output and transiently raised systemic blood-pressure . In contrast , isosorbide dinitrate was accompanied by a reduction in systemic blood-pressure and peripheral resistance with the result that the cardiac output was not decreased despite a large fall in the pulmonary vascular and left heart filling pressures . These results indicate that reduction of excessive preload by venodilatation may be haemodynamically superior to that induced by diuresis in terms of both Output:	There was no consistent evidence to support a difference in AHFS patients receiving intravenous nitrate vasodilator therapy or alternative interventions with regard to the following secondary outcome measures : SBP change after 30 and 60 minutes , heart rate change after 90 minutes , and PAOP change after 90 minutes . There appears to be no significant difference between nitrate vasodilator therapy and alternative interventions in the treatment of AHFS , with regard to symptom relief and haemodynamic variables . Nitrates may be associated with a lower incidence of adverse effects after three hours compared with placebo .
MS21390	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Acute renal failure ( ARF ) is associated with high mortality . Presently , no specific therapy for ARF exists . Therefore , early detection of ARF is critical to prevent its progression . However , serum creatinine , the st and ard marker to detect ARF , demonstrates major limitations . We prospect ively evaluated whether serum cystatin C detected ARF earlier than serum creatinine . METHODS In 85 patients at high risk to develop ARF , serum creatinine and cystatin C were determined daily . ARF was defined according to the Risk of renal dysfunction , Injury to the kidney , Failure of kidney function , Loss of kidney function , and ESRD ( RIFLE ) classification when creatinine increased by > /=50 % ( R- criteria ) , by > /=100 % ( I- criteria ) , or by > /=200 % ( F- criteria ) . In analogy , ARF was detected when cystatin C increased by > /=50 % , by > /=100 % , or by > /=200 % . RESULTS Forty-four patients developed ARF and 41 served as controls . In ARF by R- , I- , and F- criteria , the increase of cystatin C significantly preceded that of creatinine . Specifically , serum cystatin C increased already by > /=50 % 1.5 + /- 0.6 days earlier compared to creatinine . Serum cystatin C demonstrated a high diagnostic value to detect ARF as indicated by area under the curve of the ROC analysis of 0.82 and 0.97 on the two days before the R- criteria was fulfilled by creatinine . Cystatin C detected ARF according to the R- criteria with a sensitivity of 55 % and 82 % on these days , respectively . Cystatin C also performed excellently , detecting ARF defined by the I- and F- criteria two days prior to creatinine , and moderately well predicting renal replacement therapy in the further course of ARF . Additionally , low T(3)- or T(3)/T(4 ) syndrome , glucocorticoid deficiency and excess did not affect cystatin C levels , adding to its usefulness in critically ill patients with ARF . CONCLUSION Serum cystatin C is a useful detection marker of ARF , and may detect ARF one to two days earlier than creatinine We hypothesized that neutrophil gelatinase-associated lipocalin ( NGAL ) is an early predictive biomarker of contrast-induced nephropathy ( CIN ) . We prospect ively enrolled 91 children ( age 0–18 years ) with congenital heart disease undergoing elective cardiac catheterization and angiography with contrast administration ( CC ; Ioversol ) . Serial urine and plasma sample s were analyzed in a double-blind fashion by NGAL enzyme-linked immunosorbent assay ( ELISA ) . CIN , defined as a 50 % increase in serum creatinine from baseline , was found in 11 subjects ( 12 % ) , but detection using increase in serum creatinine was only possible 6–24 h after CC . In contrast , significant elevation of NGAL concentrations in urine ( 135 ± 32 vs. 11.6 ± 2 ng/ml without CIN , p < 0.001 ) and plasma ( 151 ± 34 vs. 36 ± 4 without CIN , p < 0.001 ) were noted within 2 h after CC in those subjects . Using a cutoff value of 100 ng/ml , sensitivity , specificity , and area under the receiver-operating characteristic ( ROC ) curve for prediction of CIN were excellent for the 2-h urine NGAL ( 73 % , 100 % , and 0.92 , respectively ) and 2-h plasma NGAL ( 73 % , 100 % , and 0.91 , respectively ) . By multivariate analysis , the 2-h NGAL concentrations in the urine ( R2 = 0.52 , p < 0.0001 ) and plasma ( R2 = 0.72 , p < 0.0001 ) were found to be powerful independent predictors of CIN . Patient demographics and contrast volume were not predictive of CIN Introduction Serum creatinine is a late marker of acute kidney injury ( AKI ) . Urine neutrophil gelatinase-associated lipocalin ( uNGAL ) is an early marker of AKI , where the timing of kidney injury is known . It is unknown whether uNGAL predicts AKI in the general critical care setting . We assessed the ability of uNGAL to predict AKI development and severity in critically ill children . Methods This was a prospect i ve cohort study of critically ill children . Children aged between 1 month and 21 years who were mechanically ventilated and had a bladder catheter inserted were eligible . Patients with end-stage renal disease or who had just undergone kidney transplantation were excluded . Patients were enrolled within 24 to 48 hours of initiation of mechanical ventilation . Clinical data and serum creatinine were collected daily for up to 14 days from enrollment , and urine was collected once daily for up to 4 days for uNGAL measurement . AKI was grade d using pRIFLE ( pediatric modified Risk , Injury , Failure , Loss , End Stage Kidney Disease ) criteria . Day 0 was defined as the day on which the AKI initially occurred , and pRIFLEmax was defined as the worst pRIFLE AKI grade recorded during the study period . The χ2 test was used to compare associations between categorical variables . Mann-Whitney and Kruskal-Wallis tests were used to compare continuous variables between groups . Diagnostic characteristics were evaluated by calculating sensitivity and specificity , and constructing receiver operating characteristic curves . Results A total of 140 patients ( 54 % boys , mean ± st and ard deviation Pediatric Risk of Mortality II score 15.0 ± 8.0 , 23 % sepsis ) were included . Mean and peak uNGAL concentrations increased with worsening pRIFLEmax status ( P < 0.05 ) . uNGAL concentrations rose ( at least sixfold higher than in controls ) in AKI , 2 days before and after a 50 % or greater rise in serum creatinine , without change in control uNGAL . The parameter uNGAL was a good diagnostic marker for AKI development ( area under the receiver operating characteristic curve [ AUC ] 0.78 , 95 % confidence interval [ CI ] 0.62 to 0.95 ) and persistent AKI for 48 hours or longer ( AUC 0.79 , 95 % CI 0.61 to 0.98 ) , but not for AKI severity , when it was recorded after a rise in serum creatinine had occurred ( AUC 0.63 , 95 % CI 0.44 to 0.82 ) . Conclusion We found uNGAL to be a useful early AKI marker that predicted development of severe AKI in a heterogeneous group of patients with unknown timing of kidney injury Introduction Acute kidney injury ( AKI ) is a frequent complication of cardiopulmonary bypass ( CPB ) . The lack of early biomarkers has impaired our ability to intervene in a timely manner . We previously showed in a small cohort of patients that plasma neutrophil gelatinase-associated lipocalin ( NGAL ) , measured using a research enzyme-linked immunosorbent assay , is an early predictive biomarker of AKI after CPB . In this study we tested whether a point-of-care NGAL device can predict AKI after CPB in a larger cohort . Methods First , in a cross-sectional pilot study including 40 plasma sample s ( NGAL range 60 to 730 ng/ml ) and 12 calibration st and ards ( NGAL range 0 to 1,925 ng/ml ) , NGAL measurements by enzyme-linked immunosorbent assay and by Triage ® NGAL Device ( Biosite Inc. , San Diego , CA , USA ) were highly correlated ( r = 0.94 ) . Second , in a subsequent prospect i ve uncontrolled cohort study , 120 children undergoing CPB were enrolled . Plasma was collected at baseline and at frequent intervals for 24 hours after CPB , and analyzed for NGAL using the Triage ® NGAL device . The primary outcome was AKI , which was defined as a 50 % or greater increase in serum creatinine . Results AKI developed in 45 patients ( 37 % ) , but the diagnosis using serum creatinine was delayed by 2 to 3 days after CPB . In contrast , mean plasma NGAL levels increased threefold within 2 hours of CPB and remained significantly elevated for the duration of the study . By multivariate analysis , plasma NGAL at 2 hours after CPB was the most powerful independent predictor of AKI ( β = 0.004 , P < 0.0001 ) . For the 2-hour plasma NGAL measurement , the area under the curve was 0.96 , sensitivity was 0.84 , and specificity was 0.94 for prediction of AKI using a cut-off value of 150 ng/ml . The 2 hour postoperative plasma NGAL levels strongly correlated with change in creatinine ( r = 0.46 , P < 0.001 ) , duration of AKI ( r = 0.57 , P < 0.001 ) , and length of hospital stay ( r = 0.44 , P < 0.001 ) . The 12-hour plasma NGAL strongly correlated with mortality ( r = 0.48 , P = 0.004 ) and all measures of morbidity mentioned above . Conclusion Accurate measurements of plasma NGAL are obtained using the point-of-care Triage ® NGAL device . Plasma NGAL is an early predictive biomarker of AKI , morbidity , and mortality after pediatric CPB BACKGROUND The epidemiologic characteristics of children and young adults with acute kidney injury have been described in single‐center and retrospective studies . We conducted a multinational , prospect i ve study involving patients admitted to pediatric intensive care units to define the incremental risk of death and complications associated with severe acute kidney injury . METHODS We used the Kidney Disease : Improving Global Outcomes criteria to define acute kidney injury . Severe acute kidney injury was defined as stage 2 or 3 acute kidney injury ( plasma creatinine level ≥2 times the baseline level or urine output < 0.5 ml per kilogram of body weight per hour for ≥12 hours ) and was assessed for the first 7 days of intensive care . All patients 3 months to 25 years of age who were admitted to 1 of 32 participating units were screened during 3 consecutive months . The primary outcome was 28‐day mortality . RESULTS A total of 4683 patients were evaluated ; acute kidney injury developed in 1261 patients ( 26.9 % ; 95 % confidence interval [ CI ] , 25.6 to 28.2 ) , and severe acute kidney injury developed in 543 patients ( 11.6 % ; 95 % CI , 10.7 to 12.5 ) . Severe acute kidney injury conferred an increased risk of death by day 28 after adjustment for 16 covariates ( adjusted odds ratio , 1.77 ; 95 % CI , 1.17 to 2.68 ) ; death occurred in 60 of the 543 patients ( 11.0 % ) with severe acute kidney injury versus 105 of the 4140 patients ( 2.5 % ) without severe acute kidney injury ( P<0.001 ) . Severe acute kidney injury was associated with increased use of mechanical ventilation and renal‐replacement therapy . A stepwise increase in 28‐day mortality was associated with worsening severity of acute kidney injury ( P<0.001 by log‐rank test ) . Assessment of acute kidney injury according to the plasma creatinine level alone failed to identify acute kidney injury in 67.2 % of the patients with low urine output . CONCLUSIONS Acute kidney injury is common and is associated with poor outcomes , including increased mortality , among critically ill children and young adults . ( Funded by the Pediatric Nephrology Center of Excellence at Cincinnati Children 's Hospital Medical Center and others ; AWARE Clinical Trials.gov number , NCT01987921 . Acute kidney injury ( AKI ) causes increased morbidity in critically ill children and damage to the kidney , a central mediator of homeostasis in the body , affects survival . The incidence of AKI in pediatrics is significant and despite alarming data , therapeutic interventions have failed to effect a meaningful difference in outcomes . In this review , we will discuss the epidemiology of AKI in pediatrics , treatment strategies attempted to date , experimental therapies targeting molecular patterns associated with AKI , and highlight the needed direction of AKI research and management . Prospect i ve trials in pediatrics are needed to test the validity of diagnostic tools , to identify the point of most efficacious intervention , and to underscore the therapies that can be effective in the different downstream effects of AKI Acute kidney injury ( AKI ) occurs commonly after pediatric cardiac surgery and associates with poor outcomes . Biomarkers may help the prediction or early identification of AKI , potentially increasing opportunities for therapeutic interventions . Here , we conducted a prospect i ve , multicenter cohort study involving 311 children undergoing surgery for congenital cardiac lesions to evaluate whether early postoperative measures of urine IL-18 , urine neutrophil gelatinase-associated lipocalin ( NGAL ) , or plasma NGAL Output:	Conclusion The data suggest that NGAL levels can be an important biomarker for the early detection of AKI in children
MS21391	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Since initial reports of its association with ischemic stroke appeared in 1988 , there has been continued controversy regarding the existence and strength of the association between patent foramen ovale ( PFO ) and ischemic stroke . Many case-control studies have reported an association between incident cryptogenic ischemic stroke and PFO , yet population -based studies have failed to confirm this association . Studies of the risk of recurrent stroke in patients with cryptogenic stroke with or without PFO have not shown an increased risk of recurrent stroke in patients with PFO . Meanwhile , use of devices to close PFOs and atrial septal defects percutaneously has increased dramatically since their introduction . Completion of the r and omized clinical trials of PFO closure currently in progress is vital to determine if the benefits of PFO closure in cryptogenic stroke outweigh its risks BACKGROUND Whether closure of a patent foramen ovale is effective in the prevention of recurrent ischemic stroke in patients who have had a cryptogenic stroke is unknown . We conducted a trial to evaluate whether closure is superior to medical therapy alone in preventing recurrent ischemic stroke or early death in patients 18 to 60 years of age . METHODS In this prospect i ve , multicenter , r and omized , event-driven trial , we r and omly assigned patients , in a 1:1 ratio , to medical therapy alone or closure of the patent foramen ovale . The primary results of the trial were analyzed when the target of 25 primary end-point events had been observed and adjudicated . RESULTS We enrolled 980 patients ( mean age , 45.9 years ) at 69 sites . The medical-therapy group received one or more antiplatelet medications ( 74.8 % ) or warfarin ( 25.2 % ) . Treatment exposure between the two groups was unequal ( 1375 patient-years in the closure group vs. 1184 patient-years in the medical-therapy group , P=0.009 ) owing to a higher dropout rate in the medical-therapy group . In the intention-to-treat cohort , 9 patients in the closure group and 16 in the medical-therapy group had a recurrence of stroke ( hazard ratio with closure , 0.49 ; 95 % confidence interval [ CI ] , 0.22 to 1.11 ; P=0.08 ) . The between-group difference in the rate of recurrent stroke was significant in the prespecified per- protocol cohort ( 6 events in the closure group vs. 14 events in the medical-therapy group ; hazard ratio , 0.37 ; 95 % CI , 0.14 to 0.96 ; P=0.03 ) and in the as-treated cohort ( 5 events vs. 16 events ; hazard ratio , 0.27 ; 95 % CI , 0.10 to 0.75 ; P=0.007 ) . Serious adverse events occurred in 23.0 % of the patients in the closure group and in 21.6 % in the medical-therapy group ( P=0.65 ) . Procedure-related or device-related serious adverse events occurred in 21 of 499 patients in the closure group ( 4.2 % ) , but the rate of atrial fibrillation or device thrombus was not increased . CONCLUSIONS In the primary intention-to-treat analysis , there was no significant benefit associated with closure of a patent foramen ovale in adults who had had a cryptogenic ischemic stroke . However , closure was superior to medical therapy alone in the prespecified per- protocol and as-treated analyses , with a low rate of associated risks . ( Funded by St. Jude Medical ; RESPECT Clinical Trials.gov number , NCT00465270 . ) Background and Purpose The etiology of ischemic stroke affects prognosis , outcome , and management . Trials of therapies for patients with acute stroke should include measurements of responses as influenced by subtype of ischemic stroke . A system for categorization of subtypes of ischemic stroke mainly based on etiology has been developed for the Trial of Org 10172 in Acute Stroke Treatment ( TOAST ) . Methods A classification of subtypes was prepared using clinical features and the results of ancillary diagnostic studies . “ Possible ” and “ probable ” diagnoses can be made based on the physician 's certainty of diagnosis . The usefulness and interrater agreement of the classification were tested by two neurologists who had not participated in the writing of the criteria . The neurologists independently used the TOAST classification system in their bedside evaluation of 20 patients , first based only on clinical features and then after review ing the results of diagnostic tests . Results The TOAST classification denotes five subtypes of ischemic stroke : 1 ) large-artery atherosclerosis , 2 ) cardioembolism , 3 ) small-vessel occlusion , 4 ) stroke of other determined etiology , and 5 ) stroke of undetermined etiology . Using this rating system , interphysician agreement was very high . The two physicians disagreed in only one patient . They were both able to reach a specific etiologic diagnosis in 11 patients , whereas the cause of stroke was not determined in nine . Conclusions The TOAST stroke subtype classification system is easy to use and has good interobserver agreement . This system should allow investigators to report responses to treatment among important subgroups of patients with ischemic stroke . Clinical trials testing treatments for acute ischemic stroke should include similar methods to diagnose subtypes of stroke In a prospect i ve study of 1,805 hospitalized patients in the Stroke Data Bank of the National Institute of Neurological and Communicative Disorders and Stroke , the 1,273 with infa rct ion were classified into diagnostic subtypes . Diagnosis was based on the clinical history , examination , and laboratory tests including computed tomography , noninvasive vascular imaging , and where safe and relevant , angiography . Five hundred and eight cases ( fully 40 % ) were labeled as infa rcts of undetermined cause ( IUC ) , of which 138 ( 27 % ) were evaluated with both computed tomography and angiography . The clinical syndrome and computed tomographic and angiographic findings in 91 ( 65.9 % ) of these 138 IUC cases were clearly not attributable to large‐artery thrombosis and could permit reclassification of the infa rct as due to some form of embolism . Failure to define a source of embolus kept them in the category of IUC . Thirty‐one cases ( 22.5 % ) could be reclassified as due to stenosis or thrombosis of a large artery , and 16 ( 11.6 % ) as lacunar infa rct ion . To determine if those selected for angiography among the IUC patients differed from those with other final diagnoses , a stepwise multiple logistic model was used . The most important characteristics were young age , presence of a superficial infa rct , prior transient ischemic attack , low weakness score , and presentation with a nonlacunar syndrome . The results of the model suggest that angiography use was determined by clinical characteristics uniformly across centers and not by final diagnosis . Continued use of the category IUC may help clarify risk factors and stroke subtypes , allow new mechanisms of ischemic stroke to be uncovered , and prevent classification categories of stroke used in clinical trials from becoming too broad Patients with patent foramen ovale ( PFO ) and paradoxical embolism are at increased risk for recurrent events . Percutaneous PFO closure is a new treatment modality aim ed at secondary prevention . We report the multicenter experience of interventional closure of PFO using two different devices in 272 patients . The mean age was 51 ± 14.2 years and 52.9 % were males . The implantation procedure result ed in an initial complete shunt closure rate of 74.3 % with a periprocedural complication rate of 6.6 % . There were no deaths or pericardial tamponade . The mean procedure time was less than 44 min under either conscious sedation , local or general anesthesia . This is the largest report to date demonstrating the procedural safety , reliability , and feasibility of the transcatheter PFO closure technique with the STARFlex and CardioSEAL septal implants . R and omized clinical trials are currently in progress to identify patients most likely to benefit from this intervention . Catheter Cardiovasc Interv 2004;62:512–516 . © 2004 Wiley‐Liss , OBJECTIVES We sought to assess the risk of ischemic stroke from a patent foramen ovale ( PFO ) in the multiethnic prospect i ve cohort of northern Manhattan . BACKGROUND Patent foramen ovale has been associated with increased risk of ischemic stroke , mainly in case-control studies . The actual PFO-related stroke risk in the general population is unclear . METHODS The presence of PFO was assessed at baseline by using transthoracic 2-dimensional echocardiography with contrast injection in 1,100 stroke-free subjects older than 39 years of age ( mean age 68.7 + /- 10.0 years ) from the Northern Manhattan Study ( NOMAS ) . The presence of atrial septal aneurysm ( ASA ) also was recorded . Subjects were followed annually for outcomes . We assessed PFO/ASA-related stroke risk after adjusting for established stroke risk factors . RESULTS We detected PFO in 164 subjects ( 14.9 % ) ; ASA was present in 27 subjects ( 2.5 % ) and associated with PFO in 19 subjects . During a mean follow-up of 79.7 + /- 28.0 months , an ischemic stroke occurred in 68 subjects ( 6.2 % ) . After adjustment for demographics and risk factors , PFO was not found to be significantly associated with stroke ( hazard ratio 1.64 , 95 % confidence interval [ CI ] 0.87 to 3.09 ) . The same trend was observed in all age , gender , and race-ethnic subgroups . The coexistence of PFO and ASA did not increase the stroke risk ( adjusted hazard ratio 1.25 , 95 % CI 0.17 to 9.24 ) . Isolated ASA was associated with elevated stroke incidence ( 2 of 8 , or 25 % ; adjusted hazard ratio 3.66 , 95 % CI 0.88 to 15.30 ) . CONCLUSIONS Patent foramen ovale , alone or together with ASA , was not associated with an increased stroke risk in this multiethnic cohort . The independent role of ASA needs further assessment in appositely design ed and powered studies BACKGROUND The options for secondary prevention of cryptogenic embolism in patients with patent foramen ovale are administration of antithrombotic medications or percutaneous closure of the patent foramen ovale . We investigated whether closure is superior to medical therapy . METHODS We performed a multicenter , superiority trial in 29 centers in Europe , Canada , Brazil , and Australia in which the assessors of end points were unaware of the study -group assignments . Patients with a patent foramen ovale and ischemic stroke , transient ischemic attack ( TIA ) , or a peripheral thromboembolic event were r and omly assigned to undergo closure of the patent foramen ovale with the Amplatzer PFO Occluder or to receive medical therapy . The primary end point was a composite of death , nonfatal stroke , TIA , or peripheral embolism . Analysis was performed on data for the intention-to-treat population . RESULTS The mean duration of follow-up was 4.1 years in the closure group and 4.0 years in the medical-therapy group . The primary end point occurred in 7 of the 204 patients ( 3.4 % ) in the closure group and in 11 of the 210 patients ( 5.2 % ) in the medical-therapy group ( hazard ratio for closure vs. medical therapy , 0.63 ; 95 % confidence interval [ CI ] , 0.24 to 1.62 ; P=0.34 ) . Nonfatal stroke occurred in 1 patient ( 0.5 % ) in the closure group and 5 patients ( 2.4 % ) in the medical-therapy group ( hazard ratio , 0.20 ; 95 % CI , 0.02 to 1.72 ; P=0.14 ) , and TIA occurred in 5 patients ( 2.5 % ) and 7 patients ( 3.3 % ) , respectively ( hazard ratio , 0.71 ; 95 % CI , 0.23 to 2.24 ; P=0.56 ) . CONCLUSIONS Closure of a patent foramen ovale for secondary prevention of cryptogenic embolism did not result in a significant reduction in the risk of recurrent embolic events or death as compared with medical therapy . ( Funded by St. Jude Medical ; Clinical Trials.gov number , NCT00166257 . ) Background : The optimal management of patients with cryptogenic ischemic stroke found to have a patent foramen ovale ( PFO ) at diagnostic workup remains unclear . The aims of this observational multicenter study were to evaluate : ( 1 ) the risk of recurrent cerebrovascular events in patients with cryptogenic minor ischemic stroke or transient ischemic attack ( TIA ) and PFO who either underwent percutaneous PFO closure or received only medical treatment , and ( 2 ) the risk factors associated with recurrent events . Methods : Consecutive patients ( aged 55 years or less ) with first-ever cryptogenic minor ischemic stroke or TIA and PFO were recruited in 13 Italian hospitals between January 2006 and September 2007 and followed up for 2 years . Results : 238 patients were included in the study ( mean age 42.2 ± 10.0 years ; 118 males ) ; 117 patients ( 49.2 % ) received only antithrombotic therapy while 121 patients underwent percut Output:	Safety analysis found that the overall risks for all-cause mortality and adverse events were similar in both the TDC and medical therapy groups . The combined data from recent RCTs have shown no statistically significant differences between TDC and medical therapy in the prevention of recurrent ischemic stroke . TDC closure was associated with an increased risk of atrial fibrillation but not with serious adverse events
MS21392	*TASK* the task is to summarize an input biomedical literature in six sentences *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 : The aim of this study was to evaluate the effect of combined resistance and home-based walking exercise on glycemic and metabolic control , depression and quality of life in type-2 diabetes patients . Methods : This prospect i ve study was conducted at a private hospital in Turkey . Thirty-six type-2 diabetic patients participated in the study . Subjects were r and omly distributed in one 8 week exercise intervention or in one control group . Exercise program consisted of resistance training and home-based walking . Before and after the training program , muscular strength , fasting blood glucose , hemoglobin A1C , ( HbA1C ) and plasma lipid values , quality of life and symptoms of depression of the patients were assessed . Results : Exercise group 's baseline HbA1C was significantly higher than the control groups ( p < 0.05 ) ; other blood parameters were similar between the two groups ( p>0.05 ) . At the baseline no significant differences were observed in the depression and four subscales ( physical function , physical role , bodily pain , and general health perceptions ) of the SF-36 between the exercise and control groups ( p>0.05 ) . The exercise group had higher scores of emotional role , vitality and mental health subscales than the control groups after the training programs ( p<0.05 ) . Conclusion : Exercise training which included resistance training and home- based walking could be safe , effective and beneficial in diabetic patients BACKGROUND Regular physical exercise may improve a variety of physiological and psychological factors in depressive persons . However , there is little experimental evidence to support this assumption for adolescent population s. We conducted a r and omized controlled trial to investigate the effect of physical exercise on depressive state , the excretions of stress hormones and physiological fitness variables in adolescent females with depressive symptoms . METHODS Forty-nine female volunteers ( aged 18 - 20 years ; mean 18.8 + /- 0.7 years ) with mild-to-moderate depressive symptoms , as measured by the Centre for Epidemiologic Studies Depression ( CES-D ) scale , were r and omly assigned to either an exercise regimen or usual daily activities for 8 weeks . The subjects were then crossed over to the alternate regimen for an additional 8-week period . The exercise program consisted of five 50-min sessions per week of a group jogging training at a mild intensity . The variables measured were CES-D rating scale , urinary cortisol and epinephrine levels , and cardiorespiratory factors at rest and during exercise endurance test . RESULTS After the sessions of exercise the CES-D total depressive score showed a significant decrease , whereas no effect was observed after the period of usual daily activities ( ANOVA ) . Twenty-four hour excretions of cortisol and epinephrine in urine were reduced due to the exercise regimen . The training group had a significantly reduced resting heart rate and increased peak oxygen uptake and lung capacity . CONCLUSIONS The findings of this study suggest that a group jogging exercise may be effective in improving depressive state , hormonal response to stress and physiological fitness of adolescent females with depressive symptoms Background Depression is a disabling , prevalent condition . Physical activity programs may assist depression management in older people , ameliorate co-morbid conditions and reduce the need for antidepressants . The UPLIFT pilot study assessed the feasibility of older depressed people attending a community-based progressive resistance training ( PRT ) program . The study also aim ed to determine whether PRT improves depressive status in older depressed patients . Methods A r and omised controlled trial was conducted . People aged ≥ 65 years with depressive symptoms were recruited via general practice s. Following baseline assessment , subjects were r and omly allocated to attend a local PRT program three times per week for 10 weeks or a brief advice control group . Follow-up assessment of depressive status , physical and psychological health , functional and quality of life status occurred post intervention and at six months . Results Three hundred and forty six people responded to the study invitation , of whom 22 % had depressive symptoms ( Geriatric Depression Scale , GDS-30 score ≥ 11 ) . Thirty two people entered the trial . There were no significant group differences on the GDS at follow-up . At six months there was a trend for the PRT intervention group to have lower GDS scores than the comparison group , but this finding did not reach significance ( p = 0.08 ) . More of the PRT group ( 57 % ) had a reduction in depressive symptoms post program , compared to 44 % of the control group . It was not possible to discern which specific components of the program influenced its impact , but in post hoc analyses , improvement in depressive status appeared to be associated with the number of exercise sessions completed ( r = -0.8 , p < 0.01 ) . Conclusion The UPLIFT pilot study confirmed that older people with depression can be successfully recruited to a community based PRT program . The program can be offered by existing community-based facilities , enabling its ongoing implementation for the potential benefit of other older people BACKGROUND Although exercise has been shown to relieve depression , little is known about its mechanism or dose-response characteristics . We hypothesized that high intensity progressive resistance training ( PRT ) would be more effective than either low intensity PRT or st and ard care by a general practitioner ( GP ) in depressed elderly persons , and that high intensity PRT would provide superior benefits in quality of life , sleep quality , and self-efficacy . METHODS Sixty community-dwelling adults > 60 years with major or minor depression were r and omized to supervised high intensity PRT ( 80 % maximum load ) or low intensity PRT ( 20 % maximum load ) 3 days per week for 8 weeks , or GP care . RESULTS A 50 % reduction in the Hamilton Rating Scale of Depression score was achieved in 61 % of the high intensity , 29 % of the low intensity , and 21 % of the GP care group ( p = .03 ) . Strength gain was directly associated with reduction in depressive symptoms ( r = 0.40 , p = .004 ) , as was baseline social support network type ( F = 3.52 , p = .015 ) , whereas personality type , self-efficacy , and locus of control were unrelated to the antidepressant effect . Vitality quality -of-life scale improved more in the high intensity group than in the others ( p = .04 ) . Sleep quality improved significantly in all participants ( p < .0001 ) , with the greatest relative change in high intensity PRT ( p = .05 ) . CONCLUSIONS High intensity PRT is more effective than is low intensity PRT or GP care for the treatment of older depressed patients Dance and movement therapy are consisted of music , easy exercises and sensorial stimulus and provide drugless treatment for the depression on low rates . In this study , it has been aim ed to examine the effect of dance over the depression . A total of 120 healthy male and female conservatory students ranged from 20 and 24 ages volunteered to participate in this study . They were divided r and omly into 1 of 2 groups : dance training group ( DTG ; N = 60 ) and control group ( CG ; N = 60 ) . A dance training program was applied to the subjects three days a week ( Tuesday , Thursday , and Saturday ) during 12 weeks . The subjects in the control group did not participate in the training and participated only in the pre and post test measurements . Beck Depression Scale was used for the pre and post test measurements of subjects . 12 weeks of dance training has been found to be effective on the depression levels of the subjects participating in the research as the training group ( p < 0.05 ) . The depression level of males and females before training has meaningfully decreased after 12 weeks of dance training ( p < 0.05 ) . When the depression levels of the subjects participated in research as the control group were separately evaluated for males and females , no meaningful change has been found in the depression levels during 12 weeks ( p > 0.05 ) . In conclusion , it has been seen that dance affects the depression levels of university students positively and decreases their depression levels CONTEXT Many observational studies have shown that physical activity reduces the risk of cognitive decline ; however , evidence from r and omized trials is lacking . OBJECTIVE To determine whether physical activity reduces the rate of cognitive decline among older adults at risk . DESIGN AND SETTING R and omized controlled trial of a 24-week physical activity intervention conducted between 2004 and 2007 in metropolitan Perth , Western Australia . Assessors of cognitive function were blinded to group membership . PARTICIPANTS We recruited volunteers who reported memory problems but did not meet criteria for dementia . Three hundred eleven individuals aged 50 years or older were screened for eligibility , 89 were not eligible , and 52 refused to participate . A total of 170 participants were r and omized and 138 participants completed the 18-month assessment . INTERVENTION Participants were r and omly allocated to an education and usual care group or to a 24-week home-based program of physical activity . MAIN OUTCOME MEASURE Change in Alzheimer Disease Assessment Scale-Cognitive Subscale ( ADAS-Cog ) scores ( possible range , 0 - 70 ) over 18 months . RESULTS In an intent-to-treat analysis , participants in the intervention group improved 0.26 points ( 95 % confidence interval , -0.89 to 0.54 ) and those in the usual care group deteriorated 1.04 points ( 95 % confidence interval , 0.32 to 1.82 ) on the ADAS-Cog at the end of the intervention . The absolute difference of the outcome measure between the intervention and control groups was -1.3 points ( 95 % confidence interval,-2.38 to -0.22 ) at the end of the intervention . At 18 months , participants in the intervention group improved 0.73 points ( 95 % confidence interval , -1.27 to 0.03 ) on the ADAS-Cog , and those in the usual care group improved 0.04 points ( 95 % confidence interval , -0.46 to 0.88 ) . Word list delayed recall and Clinical Dementia Rating sum of boxes improved modestly as well , whereas word list total immediate recall , digit symbol coding , verbal fluency , Beck depression score , and Medical Outcomes 36-Item Short-Form physical and mental component summaries did not change significantly . CONCLUSIONS In this study of adults with subjective memory impairment , a 6-month program of physical activity provided a modest improvement in cognition over an 18-month follow-up period . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12605000136606 The present study evaluated the effectiveness of a short-term mind-body intervention program on improving the depressive mood of an adult community sample . Forty adult volunteers with various degrees of depressive mood were r and omly assigned to the experimental group ( Dejian Mind-Body Intervention , DMBI ) and control group ( Cognitive-Behavioral Therapy , CBT ) . For each group , a total of four 90-min weekly sessions were conducted . Treatment-related changes were measured using the Beck Depression Inventory ( BDI-II ) , an electroencephalographic indicator of positive affect ( i.e. , prefrontal activation asymmetry ) , and self-report ratings on physical health . Results indicated that both the DMBI and the CBT group demonstrated significant reduction in depressive mood . However , among individuals with moderate to severe depressive mood at baseline , only those in the DMBI but not the CBT group showed significant reduction in depressive mood . Besides , only the DMBI group demonstrated a significant increase in prefrontal activation asymmetry , suggesting increase in positive affect . While most psychological therapies for depressive mood normally take several months to show treatment effect , the present findings provided initial data suggesting that the DMBI was effective in improving depressive mood of community adults after 1 month of training OBJECTIVES Based on the model by Tsang et al. ( 2002 ) which summarized the etiological factors and consequences of depression in elderly with chronic physical illnesses , a r and omized clinical trial of a special form of Qigong ( The Eight Section Brocades ) was conducted to assess if it improved the biopsychosocial health of participants . DESIGN 50 geriatric patients in sub-acute stage of chronic physical illnesses were recruited and r and omly assigned into the intervention and control group . The intervention group was given a 12-week period of Qigong practice while the control group was given traditional remedial rehabilitation activities . RESULTS The intervention group participants expressed improvement in physical health , ADL , psychological health , social relationship , and health in general as reflected by scores of the Perceived Benefit Question naire and informal feedback . CONCLUSION Although results are not significant in the generalization measures , it may be due to small effect size , small sample size , and short intervention period . Although not all of the hypotheses are supported , this report shows that Qigong ( the Eight Section Brocades ) is promising as an alternative intervention for elderly with chronic physical illness to improve their biopsychosocial health . More systematic evaluation with larger sample size and longer period of intervention is now underway in Hong Kong . Results will be reported once available We examined the effects of two physical activity modes on depressive symptoms over a 5-year period among older adults and change in physical self-esteem as a mediator of changes in depressive symptoms . Formerly sedentary , older adults ( N = 174 ) were r and omly assigned into 6-month conditions of either walking or low-intensity resistance/flexibility training . Depressive symptoms and physical self-esteem were measured before and after the 6-month intervention , and 12 and 60 months after intervention initiation . Depressive symptoms scores were decreased immediately after the intervention , followed by a sustained reduction for 12 and 60 months after intervention initiation ; there was no differential pattern of change between the physical activity modes . Change in physical self-esteem predicted change in Output:	Exercise is moderately more effective than a control intervention for reducing symptoms of depression , but analysis of method ologically robust trials only shows a smaller effect in favour of exercise . When compared to psychological or pharmacological therapies , exercise appears to be no more effective , though this conclusion is based on a few small trials
MS21393	*TASK* the task is to summarize an input biomedical literature in six sentences *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 minimum local analgesic concentration ( MLAC ) has been defined as the median effective local analgesic concentration ( EC50 ) in a 20-ml volume for epidural analgesia in the first stage of labor . The aim of this study was to determine the relative local anesthetic sparing efficacies of intravenous and epidural fentanyl by comparison of their effects on the MLAC of bupivacaine . Methods In this double-blind , r and omized , prospect i ve study , 84 parturients at ≤ 7-cm cervical dilation who requested epidural analgesia were allocated to one of two groups . After lumbar epidural catheter placement , 20 ml bupivacaine ( n = 44 ) or bupivacaine with 3 & mgr;g/ml ( 60 & mgr;g ) fentanyl ( n = 40 ) was administered . The plain bupivacaine group then received 60 & mgr;g intravenous fentanyl . The bupivacaine – fentanyl group received intravenous saline . The concentration of bupivacaine was determined by the response of the previous patient in that group to a higher or lower concentration using up – down sequential allocation . Analgesic efficacy was assessed using 100-mm visual analog pain scores , with ≤ 10 mm within 30 min defined as effective . Results The MLAC of bupivacaine – intravenous fentanyl was 0.064 % wt/vol ( 95 % confidence interval , 0.049–0.080 ) , and the MLAC of bupivacaine – epidural fentanyl was 0.034 % wt/vol ( 95 % confidence interval , 0.017–0.050 ) . Epidural fentanyl significantly increased the analgesic potency of bupivacaine by a factor of 1.88 ( 95 % confidence interval , 1.09–3.67 ) compared with intravenous fentanyl . The epidural fentanyl group demonstrated significantly higher dermatomal spread ( P = 0.0064 ) and increased pruritus ( P = 0.01 ) . Conclusions Epidural fentanyl significantly reduced the MLAC of bupivacaine when compared with intravenous fentanyl for the parturients in this study . The significantly enhanced local anesthetic sparing , dermatomal level , and pruritus with epidural fentanyl suggest a primarily spinal site of action Purpose Epidural analgesia is associated with hyperthermia during labor and presumably causes it , although no convincing mechanism has been postulated . It seems likely that fever associated with pyrogenic factors related to labor is suppressed by opioids , whereas it is expressed normally in patients given epidural analgesia . We examined this hypothesis and the possible etiology of temperature elevation in labor . Methods In this prospect i ve , r and omized , controlled study , we assessed 201 parturients during spontaneous labor . Analgesia was r and omly provided with one of four treatment groups : ( 1 ) epidural ropivacaine alone , ( 2 ) IV remifentanil alone , ( 3 ) epidural ropivacaine plus IV remifentanil , and ( 4 ) epidural ropivacaine plus IV acetaminophen . At r and omization , patients were normothermic . Intrapartum hyperthermia ( ≥38 ° C ) was correlated to the analgesic technique . Results The maximum increase in oral temperature was greatest in the ropivacaine group ( 0.7 ± 0.6 ° C ) and least in the remifentanil group ( 0.3 ± 0.4 ° C ; P = 0.013 ) . The percentage of patients who became hyperthermic ( ≥38 ° C ) during the first 6 h of labor was greatest in the ropivacaine group ( 14 % ) and least in the remifentanil-alone group ( 2 % ) , but the difference was not statistically significant . The maximum forearm-finger gradients were lower ( less vasoconstriction ) in the remifentanil group when compared to the gradients in patients with epidural analgesia ( 1.4 ± 1.8 vs 3.0 ± 1.7 , respectively ; P < 0.001 ) . Conclusion Our results are consistent with the theory that low-dose opioids inhibit fever in patients not given epidural analgesia . However , in view of the negative results , the hypothesis of epidural-induced hyperthermia may be question able BACKGROUND The pharmacokinetics of remifentanil suggests that it may be suitable for analgesia during labour . METHODS In an open pilot study , 36 women requesting meperidine for analgesia were recruited early in labour and r and omized to receive either meperidine i.m . or remifentanil given as patient-controlled analgesia ( PCA ) . Pain severity , sedation and anxiety were assessed with visual analogue scales and overall effective analgesia was assessed by the woman and midwife . RESULTS The pain scores were lower in the remifentanil group : median pain score at 60 min was 72 mm for meperidine and 48 mm for remifentanil ( P=0.004 ) and median maximum pain score during the first 2 h was 82.5 mm for the meperidine group and 66.5 mm for the remifentanil group ( P=0.009 ) . Both the midwives ' and the women 's assessment s of overall effective analgesia were higher in the remifentanil group [ Likert scale ( 5 = excellent to 1 = poor ) : chi2=12.10 , P=0.002 for mothers ' assessment ; chi2=12.80 , P=0.002 for midwives ' assessment ] . CONCLUSION In this pilot study , remifentanil by PCA gave better pain relief to mothers in labour than intramuscular meperidine . However , remifentanil is a potent respiratory depressant and adequate continuous monitoring is necessary Meptazinol and pethidine were compared in a double-blind r and omized trial with regard to analgesia during the first stage of labour . It was concluded that neither drug is effective for sustained pain relief , and that there is no advantage of one over the other . However , neither drug affected maternal condition as reflected by respiratory rate , pulse rate and blood pressure , nor was any detrimental effect noted on the condition of the newborn infant . The critical re assessment of traditional drugs for analgesia in labour is suggested Background Pain relief during labour is a topic of major interest in the Netherl and s. Epidural analgesia is considered to be the most effective method of pain relief and recommended as first choice . However its uptake by pregnant women is limited compared to other western countries , partly as a result of non-availability due to logistic problems . Remifentanil , a synthetic opioid , is very suitable for patient controlled analgesia . Recent studies show that epidural analgesia is superior to remifentanil patient controlled analgesia in terms of pain intensity score ; however there was no difference in satisfaction with pain relief between both treatments . Methods / design The proposed study is a multicentre r and omized controlled study that assesses the cost-effectiveness of remifentanil patient controlled analgesia compared to epidural analgesia . We hypothesize that remifentanil patient controlled analgesia is as effective in improving pain appreciation scores as epidural analgesia , with lower costs and easier achievement of 24 hours availability of pain relief for women in labour and efficient pain relief for those with a contraindication for epidural analgesia . Eligible women will be informed about the study and r and omized before active labour has started . Women will be r and omly allocated to a strategy based on epidural analgesia or on remifentanil patient controlled analgesia when they request pain relief during labour . Primary outcome is the pain appreciation score , i.e. satisfaction with pain relief . Secondary outcome parameters are costs , patient satisfaction , pain scores ( pain-intensity ) , mode of delivery and maternal and neonatal side effects . The economic analysis will be performed from a short-term healthcare perspective . For both strategies the cost of perinatal care for mother and child , starting at the onset of labour and ending ten days after delivery , will be registered and compared . Discussion This study , considering cost effectiveness of remifentanil as first choice analgesia versus epidural analgesia , could strongly improve the care for 180.000 women , giving birth in the Netherl and s yearly by giving them access to pain relief during labour , 24 hours a day . Trial registration numberDutch Trial Register NTR2551 , Background Whether epidural analgesia for labor prolongs the active-first and second labor stages and increases the risk of vacuum-assisted delivery is a controversial topic . Our study was conducted to answer the question : does lumbar epidural analgesia with lidocaine affect the progress of labor in our obstetric population ? Method 395 healthy , nulliparous women , at term , presented in spontaneous labor with a singleton vertex presentation . These patients were r and omized to receive analgesia either , epidural with bolus doses of 1 % lidocaine or intravenous , with meperidine 25 to 50 mg when their cervix was dilated to 4 centimeters . The duration of the active-first and second stages of labor and the neonatal apgar scores were recorded , in each patient . The total number of vacuum-assisted and cesarean deliveries were also measured . Results 197 women were r and omized to the epidural group . 198 women were r and omized to the single-dose intravenous meperidine group . There was no statistical difference in rates of vacuum-assisted delivery rate . Cesarean deliveries , as a consequence of fetal bradycardia or dystocia , did not differ significantly between the groups . Differences in the duration of the active-first and the second stages of labor were not statistically significant . The number of newborns with 1-min and 5-min Apgar scores less than 7 , did not differ significantly between both analgesia groups . Conclusion Epidural analgesia with 1 % lidocaine does not prolong the active-first and second stages of labor and does not increase vacuum-assisted or cesarean delivery rate A double-blind between-patient study was carried out comparing pentazocine with pethidine in 94 women in labour . Similar analgesic and sedative effects were obtained with the two drugs , and Apgar scores were similar for babies of both drug groups . Fewer emetic sequelae were reported after pentazocine injections , though there was no statistically significant difference between the two drug groups in incidence of other side-effects The perfect analgesic regimen is constantly sought , no matter how labor is conducted . The quest for an effective drug that will afford maximum relaxation and pain relief with minimum interruption of any natural homeostatic mechanism is a foremost subject in present obstetric analgesics research . Synthetic alternatives are being offered , promising perfect compatibility with the clinician 's dem and s. Nalbuphine , a semisynthetic narcotic agonist-antagonist analgesic of the penanthren series , is supposed not to be liable to cause respiratory depression and is expected to have fewer side effects . A double-blind , r and omised prospect i ve study of 137 patients who received 10 mg nalbuphine or 50 mg pethidine i.v . during the active phase of labor in term was carried out . Maternal cardiovascular variables , pain intensity , progress of labor and fetal heart rate during labor were related to side effect and neonatal outcome ( 1- and 5-min Apgar scores and umbilical venous pH ) . Neither regimen showed an advantage over the other . Data analysis points to a possible transient depressive effect induced by nalbuphine on the fetal or neonatal central nervous system Objective . To characterize different methods of monitoring neonatal effects associated with maternal opioid analgesia . Special focus was on the static-charge-sensitive bed ( SCSB ) , which could potentially serve as a non-invasive neonatal monitor . Methods . 12 healthy , term newborns from normal pregnancies were included in this prospect i ve , r and omized , controlled study . Maternal labor analgesia was either intravenous fentanyl ( n= 5 ) or paracervical bupivacaine blockade ( n= 7 ) . Neonatal recording from delivery to the age of 12 hours included continuous SCSB monitoring with ECG and oximeter for sleep states , respiration , oxygenation , heart rate , and body movements . In addition , umbilical blood pH , Apgar , Amiel-Tison 's Neurologic and Adaptive Capacity Scoring ( NACS ) , skin cyanosis scoring , blood pressure , rectal and skin temperatures , and skin blood flow measurements were performed . Results . The study was interrupted , because one baby in the fentanyl group had a significant decrease in oxyhemoglobin saturation ( SpO2 ) to 59 % . This was considered to be residual effect of fentanyl and was treated with naloxone . SpO2 was generally lower in the fentanyl group . Epochs with SpO2 < 90 % were more frequent in the fentanyl group , especially during active sleep ( mean ± SD11.9 ± 10.7 % vs. 2.0 ± 1.7 % of epochs , p= 0.034 ) . Mean heart rate values were lower in the fentanyl group ( 121.1 ± 6.4 vs. 132.6 ± 6.8 beats per minute , p= 0.02 ) , and this difference was seen during wake and all sleep states . Maximum heart rate values were lower in the fentanyl group , too . The opiate group had less quiet sleep than controls ( 9.6 ±2.8 % vs. 18.3 ± 8.3 % , p = 0.0 Output:	Pain scores ( reduction in visual analogue scale ( VAS ) score of at least 40 mm : 50 women ; 1 trial ; RR 25 , 95 % CI 1.56 to 400 , low- quality evidence ) and pain measured in labour ( women reporting pain relief to be " good " or " fair " within one hour of administration : 116 women ; 1 trial ; RR 1.75 , 95 % CI 1.24 to 2.47 , low- quality evidence ) were both reduced in the pethidine group , and fewer women requested any additional analgesia ( 50 women ; 1 trial ; RR 0.71 , 95 % CI 0.54 to 0.94 , low- quality evidence ) .There was limited information on adverse effects and harm to women and babies . There were few results that clearly showed that one opioid was more effective than another . Overall , findings indicated that parenteral opioids provided some pain relief and moderate satisfaction with analgesia in labour . Opioid drugs were associated with maternal nausea , vomiting and drowsiness , although different opioid drugs were associated with different adverse effects . There was no clear evidence of adverse effects of opioids on the newborn . We did not have sufficient evidence to assess which opioid drug provided the best pain relief with the least adverse effects . AUTHORS ' CONCLUSIONS Though most evidence is of low- or very-low quality , for healthy women with an uncomplicated pregnancy who are giving birth at 37 to 42 weeks , parenteral opioids appear to provide some relief from pain in labour but are associated with drowsiness , nausea , and vomiting in the woman . Effects on the newborn are unclear . Maternal satisfaction with opioid analgesia was largely unreported .
MS21394	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Aims : Severe preterm fetal growth restriction ( FGR ) remote from term is problematic . We aim ed to investigate the effect of maternally-administered antithrombin on maternal and neonatal outcomes . A prospect i ve , one-arm , pilot study was performed in 14 women with severe FGR ( ≤5th centile ) at < 28 weeks of gestation , without hypertensive disorders . Maternal plasma concentrations of soluble Feline McDonough Sarcoma (FMS)-like trypsin kinase-1 ( sFlt-1 ) and placental growth factor ( PlGF ) were measured and categorized into three groups : group 1 ; low sFlt-1 and high PlGF , group 2 ; moderate sFlt-1 and low PlGF , and group 3 ; high sFlt-1 and low PlGF . Antithrombin was administered for 3 days . The incidence of perinatal mortality , infant morbidity , and the period of pregnancy prolongation were compared . Results : In group 1 ( n=4 ) , their pregnancies were extended for longer periods and the maternal and infant outcomes were good . The prolongation periods were shorter in groups 2 ( n=3 ) and 3 ( n=7 ) , which result ed in poor maternal [ severe preeclampsia or hemolysis , elevated liver enzymes , and low platelet count ( HELLP ) syndrome ] and infant outcomes . Conclusions : The evaluation of the maternal sFlt-1 and PlGF at 21–27 weeks of gestation is useful in the managements of severe FGR . Antithrombin treatment could prolong the pregnancies with low sFlt-1 and high PlGF without negatively affecting maternal or fetal health BACKGROUND No consensus exists for the best way to monitor and when to trigger delivery in mothers of babies with fetal growth restriction . We aim ed to assess whether changes in the fetal ductus venosus Doppler waveform ( DV ) could be used as indications for delivery instead of cardiotocography short-term variation ( STV ) . METHODS In this prospect i ve , European multicentre , unblinded , r and omised study , we included women with singleton fetuses at 26 - 32 weeks of gestation who had very preterm fetal growth restriction ( ie , low abdominal circumference [ < 10th percentile ] and a high umbilical artery Doppler pulsatility index [ > 95th percentile ] ) . We r and omly allocated women 1:1:1 , with r and omly sized blocks and stratified by participating centre and gestational age ( < 29 weeks vs ≥29 weeks ) , to three timing of delivery plans , which differed according to antenatal monitoring strategies : reduced cardiotocograph fetal heart rate STV ( CTG STV ) , early DV changes ( pulsatility index > 95th percentile ; DV p95 ) , or late DV changes ( A wave [ the deflection within the venous waveform signifying atrial contraction ] at or below baseline ; DV no A ) . The primary outcome was survival without cerebral palsy or neurosensory impairment , or a Bayley III developmental score of less than 85 , at 2 years of age . We assessed outcomes in surviving infants with known outcomes at 2 years . We did an intention to treat study for all participants for whom we had data . Safety outcomes were deaths in utero and neonatal deaths and were assessed in all r and omly allocated women . This study is registered with IS RCT N , number 56204499 . FINDINGS Between Jan 1 , 2005 and Oct 1 , 2010 , 503 of 542 eligible women were r and omly allocated to monitoring groups ( 166 to CTG STV , 167 to DV p95 , and 170 to DV no A ) . The median gestational age at delivery was 30·7 weeks ( IQR 29·1 - 32·1 ) and mean birthweight was 1019 g ( SD 322 ) . The proportion of infants surviving without neuroimpairment did not differ between the CTG STV ( 111 [ 77 % ] of 144 infants with known outcome ) , DV p95 ( 119 [ 84 % ] of 142 ) , and DV no A ( 133 [ 85 % ] of 157 ) groups ( ptrend=0·09 ) . 12 fetuses ( 2 % ) died in utero and 27 ( 6 % ) neonatal deaths occurred . Of survivors , more infants where women were r and omly assigned to delivery according to late ductus changes ( 133 [ 95 % ] of 140 , 95 % , 95 % CI 90 - 98 ) were free of neuroimpairment when compared with those r and omly assigned to CTG ( 111 [ 85 % ] of 131 , 95 % CI 78 - 90 ; p=0.005 ) , but this was accompanied by a non-significant increase in perinatal and infant mortality . INTERPRETATION Although the difference in the proportion of infants surviving without neuroimpairment was non-significant at the primary endpoint , timing of delivery based on the study protocol using late changes in the DV waveform might produce an improvement in developmental outcomes at 2 years of age . FUNDING ZonMw , The Netherl and s and Dr Hans Ludwig Geisenhofer Foundation , Germany OBJECTIVE The objective of the study was to describe neurodevelopmental outcome at the age of 4.5 years in 216 children , born after expectant management of severe early-onset hypertensive complications of pregnancy . STUDY DESIGN This was a prospect i ve follow-up study until age 4.5 years from maternal admission onward . Developmental outcome measurements included child intelligence quotient and behavioral , motor , and neurological outcome . Abnormal composite outcome ( perinatal mortality or abnormal developmental outcome ) was studied in relation to gestational age ( GA ) , birthweight ( BW ) , and perinatal variables . RESULTS Fetal and neonatal mortality was 9 % and 8 % , respectively . Of the 178 survivors , 149 ( 84 % ) were seen for follow-up . Mean GA was 31.4 weeks and 90 % were born growth restricted . Abnormal developmental outcome occurred in 20 % and abnormal composite outcome in 37 % . CONCLUSION Perinatal mortality or abnormal child development occurs in one third of pregnancies with early-onset and severe hypertensive complications and is highest in the lowest GA and BW ranges OBJECTIVES Few data exist for counseling and perinatal management of women after an antenatal diagnosis of early-onset fetal growth restriction . Yet , the consequences of preterm delivery and its attendant morbidity for both mother and baby are far reaching . The objective of this study was to describe perinatal morbidity and mortality following early-onset fetal growth restriction based on time of antenatal diagnosis and delivery . METHODS We report cohort outcomes for a prospect i ve multicenter r and omized management study of fetal growth restriction ( Trial of R and omized Umbilical and Fetal Flow in Europe ( TRUFFLE ) ) performed in 20 European perinatal centers between 2005 and 2010 . Women with a singleton fetus at 26 - 32 weeks of gestation , with abdominal circumference < 10(th ) percentile and umbilical artery Doppler pulsatility index > 95(th ) percentile , were recruited . The main outcome measure was a composite of fetal or neonatal death or severe morbidity : survival to discharge with severe brain injury , bronchopulmonary dysplasia , proven neonatal sepsis or necrotizing enterocolitis . RESULTS Five-hundred and three of 542 eligible women formed the study group . Mean ± SD gestational age at diagnosis was 29 ± 1.6 weeks and mean ± SD estimated fetal weight was 881 ± 217 g ; 12 ( 2.4 % ) babies died in utero . Gestational age at delivery was 30.7 ± 2.3 weeks , and birth weight was 1013 ± 321 g. Overall , 81 % of deliveries were indicated by fetal condition and 97 % were by Cesarean section . Of 491 liveborn babies , outcomes were available for 490 amongst whom there were 27 ( 5.5 % ) deaths and 118 ( 24 % ) babies suffered severe morbidity . These babies were smaller at birth ( 867 ± 251 g ) and born earlier ( 29.6 ± 2.0 weeks ) . Death and severe morbidity were significantly related to gestational age , both at study entry and delivery and also with the presence of maternal hypertensive morbidity . The median time to delivery was 13 days for women without hypertension , 8 days for those with gestational hypertension , 4 days for pre-eclampsia and 3 days for HELLP syndrome . CONCLUSIONS Fetal outcome in this study was better than expected from contemporary reports : perinatal death was uncommon ( 8 % ) and 70 % survived without severe neonatal morbidity . The intervals to delivery , death and severe morbidity were related to the presence and severity of maternal hypertensive conditions OBJECTIVE To test the effect of aspirin and omega 3 on fetal weight as well as feto-maternal blood flow in asymmetrical intrauterine growth restriction ( IUGR ) . STUDY DESIGN This study is a clinical ly registered ( NCT02696577 ) , open , parallel , r and omized controlled trial , conducted at Assiut Woman 's Health Hospital , Egypt including 80 pregnant women ( 28 - 30 weeks ) with IUGR . They were r and omized either to group I : aspirin or group II : aspirin plus omega 3 . The primary outcome was the fetal weight after 6 weeks of treatment . Secondary outcomes included Doppler blood flow changes in both uterine and umbilical arteries , birth weight , time and method of delivery and admission to NICU . The outcome variables were analyzed using paired and unpaired t-test . RESULTS The estimated fetal weight increased significant in group II more than group I ( p=0.00 ) . The uterine and umbilical arteries blood flow increased significantly in group II ( p<0.05 ) . The birth weight in group II was higher than that observed in group I ( p<0.05 ) . CONCLUSION The using of aspirin with omega 3 is more effective than using aspirin only in increasing fetal weight and improving utero-placental blood flow in IUGR AIM We design ed a safety and dose-finding trial of tadalafil administered for fetal growth restriction ( FGR ) . METHODS Three cases were initially commenced on 10 mg/day and monitored for major adverse events . Should a major adverse event be observed in one or more of the three cases , an examination into its relation with tadalafil would be conducted by a safety evaluation committee . If one or more of these new cases exhibited the same adverse event , the trial would be stopped completely . If there were no harmful side-effects , the trial would be extended to three cases at 20 mg/day , and the protocol would continue as in the 10-mg/day dose . The 40-mg/day dosage was tried in six cases as the dosage was considered to be high . RESULTS The study population consisted of pregnant women with FGR . Maternal adverse events in all doses were recorded as least one grade 1 adverse events , as tadalafil was considered acceptable from the viewpoint of the mothers . However , a dose of 40 mg/day increased the number of grade 1 adverse events . The only fetal adverse event was a case of intrauterine fetal death related to the velamentous insertion of the umbilical cord . Neonatal adverse events showed no correlation to tadalafil dose , but were found more frequently in preterm births and , therefore , were correlated to infant prematurity . CONCLUSION This safety and dose-finding trial showed that tadalafil had a favorable safety profile for pregnant women and fetuses with FGR AIM The prognosis for severe fetal growth restriction ( FGR ) with severe oligohydramnios before 26 weeks ' gestation ( WG ) is currently poor ; furthermore , its management is controversial . We report the innovative new management of FGR , such as therapeutic amnioinfusion and tocolysis . MATERIAL AND METHODS For FGR and severe oligohydramnios before 26 WG complicated with absent or reversed umbilical artery end-diastolic flow velocity and /or deceleration by ultrasonography , we performed transabdominal amnioinfusion with tocolysis . Cases with multiple anomalies were excluded . Survival rate and long-term prognosis were analyzed . RESULTS Among 570 FGR cases , 18 were included in the study . Mean diagnosis and delivery were at 22.6 ± 2.0 and 28.7 ± 3.3 WG . Median birthweight was 625 g ( -4.2 st and ard deviation ) . Final survival rate was 11/13 ( 85 % ) . There were five fetal deaths . In seven cases , oligohydramnios improved . Growth was detected in 10/18 fetuses . Furthermore , 8/8 decelerations , 4/12 cases of reversed umbilical artery end-diastolic flow velocity , 7/14 cases of brain-sparing effect , and 6/13 venous Doppler abnormalities were improved . When we detected umbilical cord compression , 8/10 cases were rescued . Eleven infants were followed up for an average of 5 years ; one case of cerebral palsy with normal development and Output:	Neurodevelopmental impairment was assessed in a minority of surviving children .
MS21395	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objective : To assess the efficacy of an innovative smoking cessation intervention targeted to a multiethnic , economically disadvantaged HIV-positive population . Design : A two-group r and omized clinical trial compared a smoking cessation intervention delivered by cellular telephone with usual care approach . Methods : Current smokers from a large , inner city HIV/AIDS care center were recruited and r and omized to receive either usual care or a cellular telephone intervention . The usual care group received brief physician advice to quit smoking , targeted self-help written material s and nicotine replacement therapy . The cellular telephone intervention received eight counseling sessions delivered via cellular telephone in addition to the usual care components . Smoking-related outcomes were assessed at a 3-month follow-up . Results : The trial had 95 participants and 77 ( 81.0 % ) completed the 3-month follow-up assessment . Analyses indicated biochemically verified point prevalence smoking abstinence rates of 10.3 % for the usual care group and 36.8 % for the cellular telephone group ; participants who received the cellular telephone intervention were 3.6 times ( 95 % confidence interval , 1.3 - 9.9 ) more likely to quit smoking compared with participants who received usual care ( P = 0.0059 ) . Conclusions : These results suggest that individuals living with HIV/AIDS are receptive to , and can be helped by , smoking cessation treatment . In addition , smoking cessation treatment tailored to the special needs of individuals living with HIV/AIDS , such as counseling delivered by cellular telephone , can significantly increase smoking abstinence rates over that achieved by usual care Background Advances in technology allowed the development of a novel smoking cessation program delivered by video messages sent to mobile phones . This social cognitive theory-based intervention ( called “ STUB IT ” ) used observational learning via short video diary messages from role models going through the quitting process to teach behavioral change techniques . Objective The objective of our study was to assess the effectiveness of a multimedia mobile phone intervention for smoking cessation . Methods A r and omized controlled trial was conducted with 6-month follow-up . Participants had to be 16 years of age or over , be current daily smokers , be ready to quit , and have a video message-capable phone . Recruitment targeted younger adults predominantly through radio and online advertising . Registration and data collection were completed online , prompted by text messages . The intervention group received an automated package of video and text messages over 6 months that was tailored to self-selected quit date , role model , and timing of messages . Extra messages were available on dem and to beat cravings and address lapses . The control group also set a quit date and received a general health video message sent to their phone every 2 weeks . Results The target sample size was not achieved due to difficulty recruiting young adult quitters . Of the 226 r and omized participants , 47 % ( 107/226 ) were female and 24 % ( 54/226 ) were Maori ( indigenous population of New Zeal and ) . Their mean age was 27 years ( SD 8.7 ) , and there was a high level of nicotine addiction . Continuous abstinence at 6 months was 26.4 % ( 29/110 ) in the intervention group and 27.6 % ( 32/116 ) in the control group ( P = .8 ) . Feedback from participants indicated that the support provided by the video role models was important and appreciated . Conclusions This study was not able to demonstrate a statistically significant effect of the complex video messaging mobile phone intervention compared with simple general health video messages via mobile phone . However , there was sufficient positive feedback about the ease of use of this novel intervention , and the support obtained by observing the role model video messages , to warrant further investigation . Trial registration Australian New Zeal and Clinical Trials Registry Number : ACTRN12606000476538 ; http://www.anzctr.org.au/trial_view.aspx?ID=81688 ( Archived by WebCite at http://www.webcitation.org/5umMU4sZi Summary We evaluated the effectiveness of a mobile phone text-messaging based smoking cessation intervention package among Chinese adolescent smokers . Students aged 16–19 years were recruited from six vocational high schools located in Shanghai . We assigned the six schools to an intervention group or a control group by cluster r and omization . The 92 participants in the intervention group were given tailored information via mobile phone text-messaging for 12 weeks . The 87 participants in the control group were provided with a self-help pamphlet about smoking cessation instead . After the intervention , attitudes towards the disadvantages of smoking were significantly improved , and the level of nicotine dependence and cigarette dependence significantly decreased in the intervention group . The intervention group had a relatively higher self-reported 7-day abstinence compared to the control group and 30-day abstinence , but the differences were not significant . However , the intervention group had a significantly higher rate of smoking reduction ( 66 % vs. 35 % ) and moving forward in quitting stages ( 52 % vs. 18 % ) compared to the control group . The interactive and tailored assistance provided by the mobile phone text-messaging was effective in smoking behaviour intervention in Chinese adolescent smokers Mounting evidence suggests that smokers living with HIV/AIDS have a significantly increased risk of numerous adverse health outcomes ( both AIDS- and non-AIDS-related ) compared with HIV-positive nonsmokers . Therefore , efforts to design and implement effective cessation programs for this ever-growing special population are warranted . The present study assessed the effects of a cell phone intervention ( CPI ) on hypothesized mediators ( i.e. , changes in depression , anxiety , social support , and self-efficacy ) demonstrated to influence cessation outcomes in other population s. Ninety-five participants from an inner-city AIDS clinic were r and omized to receive either the CPI or recommended st and ard of care ( RSOC ) smoking cessation treatment . Participants r and omized to the RSOC group ( n=47 ) received brief advice to quit , a 10-week supply of nicotine patches , and self-help material s. Participants r and omized to the CPI group ( n=48 ) received RSOC components plus a series of eight proactive counseling sessions delivered via cell phones . A series of regression analyses ( linear and logistic ) was used to assess the relationships between treatment group , the hypothesized mediators , and biochemically confirmed smoking cessation outcomes . Results indicated that the CPI group experienced greater reductions in anxiety and depression , and increases in self-efficacy compared with the RSOC group . Further , changes in depression , anxiety , and self-efficacy weakened the association between treatment group and cessation outcome . The mediator hypothesis , however , for social support was rejected , as the difference score was not significantly associated with treatment group . These results suggest that the efficacy of the CPI is at least partially mediated by its ability to decrease symptoms of distress while increasing self-efficacy The psychological construct , readiness to change , is established as a central construct within behavioral change theories such as motivational interviewing ( MI ) . Less is known about the interplay of mechanisms for change within adolescent treatment population s. Underst and ing the timing and interactive influence that adolescents ' readiness to stop smoking and peer smoking have on subsequent tobacco use is important to advance intervention research . Toward this end , we used ecological momentary assessment ( EMA ) data from an automated texting smoking intervention r and omized controlled trial to model the interactive effects of readiness to stop smoking and friends smoking on adolescent tobacco use . Two hundred adolescents were r and omized into experimental treatment or attention control conditions , provided smart phones , and were followed for 6 months . African American youth represented the majority of the sample . We collected monthly EMA data for 6 months on friends smoking and readiness to stop smoking as well as survey outcome data . We tested a moderated mediation model using bias corrected bootstrapping to determine if the indirect effect of treatment on cigarettes smoked through readiness to stop smoking was moderated by friends smoking . Findings revealed that readiness to stop smoking mediated the effects of treatment on cigarettes smoked for those adolescents with fewer friends smoking , but not for those with more friends smoking . These results support importance of peer-focused interventions with urban adolescents and provide target mechanisms for future research Background Although supporting lifestyle change is an effective way of preventing further events in people with cardiovascular disease , providing access to such interventions is a major challenge . This study aims to investigate whether simple reminders about behaviour change sent via mobile phone text message decrease cardiovascular risk . Methods and analysis R and omised controlled trial with 6 months of follow-up to evaluate the feasibility , acceptability and effect on cardiovascular risk of repeated lifestyle reminders sent via mobile phone text messages compared to usual care . A total of 720 patients with coronary artery disease will be r and omised to either st and ard care or the TEXT ME intervention . The intervention group will receive multiple weekly text messages that provide information , motivation , support to quit smoking ( if relevant ) and recommendations for healthy diets and exercise . The primary end point is a change in plasma low-density lipoprotein cholesterol at 6 months . Secondary end points include a change in systolic blood pressure , smoking status , quality of life , medication adherence , waist circumference , physical activity levels , nutritional status and mood at 6 months . Process outcomes related to acceptability and feasibility of TEXT ME will also be collected . Ethics and dissemination Primary ethics approval was received from Western Sydney Local Health Network Human Research Ethics Committee — Westmead . Results will be disseminated via the usual scientific forums including peer- review ed publications and presentations at international conferences . Clinical trials registration number ACTRN12611000161921 INTRODUCTION Substantial evidence indicates that cigarette smoking among people living with HIV/AIDS ( PLWHA ) represents a significant public health concern . However , few efforts to assess smoking cessation interventions targeting this population have been reported . In this brief report , 3-month outcomes from an ongoing treatment trial for PLWHA who smoke are described . METHODS Study participants were recruited from a large HIV care center serving a diverse population of PLWHA . A two-group r and omized design was used to compare the efficacy of usual-care ( UC ) smoking cessation treatment versus a cell phone intervention ( CPI ) . Follow-ups were conducted at the HIV clinic 3 months postenrollment . Using an intent-to-treat approach , a series of multiple regression models were used to compare smoking outcomes in the 2 groups . RESULTS Four hundred and seventy-four participants were enrolled and r and omized , UC ( n = 238 ) and CPI ( n = 236 ) . Mean age in the sample was 44.8 ( SD = 8.1 ) years , and the majority were male ( 70.0 % ) , Black ( 76.6 % ) , and had an education level of high school or less ( 77.5 % ) . At follow-up , participants in the CPI group were 4.3 ( 95 % CI = 1.9 , 9.8 ) times more likely to be abstinent ( 7 day ) compared with those in the UC group . Similarly , significant point estimates were observed for the other smoking outcomes of interest . CONCLUSIONS Findings from this preliminary report indicate that a smoking cessation intervention for PLWHA consisting of cell phone-delivered proactive counseling results in significantly higher abstinence rates compared with a st and ard care approach . Evaluation of the long-term ( 6-month and 12-month ) efficacy of the CPI approach is ongoing Background The study aims to test the differential effects of a web-based text and a web-based video-driven computer-tailored approach for lower socio-economic status ( LSES ) and higher socio-economic status ( HSES ) smokers which incorporate multiple computer-tailored feedback moments . The two programs differ only in the mode of delivery ( video- versus text-based messages ) . The paper aims to describe the development and design of the two computer-tailored programs . Methods / design Respondents who smoked at the time of the study inclusion , who were motivated to quit within the following six months and who were aged 18 or older were included in the program . The study is a r and omized control trial with a 2 ( video/text ) * 2(LSES/HSES ) design . Respondents were assigned either to one of the intervention groups ( text versus video tailored feedback ) or to the control group ( non-tailored generic advice ) . In all three conditions participants were asked to fill in the baseline question naire based on the I-Change model . The question naire assessed socio-demographics , attitude towards smoking , knowledge , self-efficacy , social influence , depression , level of addiction , action planning , goal actions , intention to quit smoking , seven-day point prevalence and continued abstinence . Follow-up measurements were conducted at six and twelve months after baseline . Discussion The present paper describes the development of the two computer-tailored smoking cessation programs , their components and the design of the study . The study results reveal different working mechanisms of multiple tailored smoking cessation interventions and will help us to gain more insight into effective strategies to target different subgroups , especially smokers with a lower socio-economic status . Trial registration Dutch Trial Register Background Despite promising data in Western countries , there is a dearth of research into the efficacy of text messaging-based smoking cessation programs in other setting s , including the Middle East , where smoking prevalence rates are higher . Objective This paper reports cessation rates observed in SMS Turkey , a text messaging-based smoking cessation program for adult smokers in Ankara , Turkey . Methods This study was a small-scale , parallel-group r and omized controlled trial ( RCT ) conducted in Ankara , Turkey . Particip Output:	There is moderate-certainty evidence that automated text message-based smoking cessation interventions result in greater quit rates than minimal smoking cessation support . There is moderate-certainty evidence of the benefit of text messaging interventions in addition to other smoking cessation support in comparison with that smoking cessation support alone .
MS21396	*TASK* the task is to summarize an input biomedical literature in six sentences *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 use of a stent to deliver a drug may reduce in-stent restenosis . Paclitaxel interrupts the smooth muscle cell cycle by stabilizing microtubules , thereby arresting mitosis . Methods and Results —On the basis of prior animal studies , the European evaLUation of the pacliTaxel Eluting Stent ( ELUTES ) pilot clinical trial ( n=190 ) investigated the safety and efficacy of V-Flex Plus coronary stents ( Cook Inc ) coated with escalating doses of paclitaxel ( 0.2 , 0.7 , 1.4 , and 2.7 & mgr;g/mm2 stent surface area ) applied directly to the abluminal surface of the stent in de novo lesions compared with bare stent alone . The primary efficacy end point was angiographic percent diameter stenosis at 6 months . At angiographic follow-up , percent diameter stenosis was 33.9±26.7 % in controls ( n=34 ) and 14.2±16.6 % in the 2.7-&mgr;g/mm2 group ( n=31 ; P = 0.006 ) . Late loss decreased from 0.73±0.73 to 0.11±0.50 mm ( P = 0.002 ) . Binary restenosis ( ≥50 % at follow-up ) decreased from 20.6 % to 3.2 % ( P = 0.056 ) , with no significant benefit from intermediate paclitaxel doses . Freedom from major adverse cardiac events in the highest ( effective ) dose group was 92 % , 89 % , and 86 % at 1 , 6 , and 12 months , respectively ( P = NS versus control ) . No late stent thromboses were seen in any treated group despite clopidogrel treatment for 3 months only . Conclusions —Paclitaxel applied directly to the abluminal surface of a bare metal coronary stent , at a dose density of 2.7 & mgr;g/mm2 , reduced angiographic indicators of in-stent restenosis without short- or medium-term side effects Background —The safety and efficacy of sirolimus-eluting stenting have been demonstrated , but the outcome of patients treated with this novel technology beyond the first year remains unknown . We sought to evaluate the angiographic , intravascular ultrasound ( IVUS ) , and clinical outcomes of patients treated with sirolimus-eluting stents 2 years after implantation . Methods and Results —This study included 30 patients treated with sirolimus-eluting Bx Velocity stenting ( slow release [ SR ] , n=15 , and fast release [ FR ] , n=15 ) in São Paulo , Brazil . Twenty-eight patients underwent 2-year angiographic and IVUS follow-up . No deaths occurred during the study period . In-stent late loss was slightly greater in the FR group ( 0.28±0.4 mm ) than in the SR group ( −0.09±0.23 mm , P = 0.007 ) . No patient had in-stent restenosis . At 2-year follow-up , only 1 patient ( FR group ) had a 52 % diameter stenosis within the lesion segment , which required repeat revascularization . The target-vessel revascularization rate for the entire cohort was 10 % ( 3/30 ) at 2 years . All other patients had ≤35 % diameter stenosis . Angiographic lumen loss at the stent edges was also minimal ( in-lesion late loss was 0.33±0.42 mm [ FR ] and 0.13±0.29 mm [ SR ] ) . In-stent neointimal hyperplasia volume , as detected by IVUS , remained minimal after 2 years ( FR= 9.90±9 mm3 and SR=10.35±9.3 mm3 ) . Conclusions —This study demonstrates the safety and efficacy of sirolimus-eluting Bx Velocity stents 2 years after implantation in humans . In-stent lumen dimensions remained essentially unchanged at 2-year follow-up in the 2 groups , although angiographic lumen loss was slightly higher in the FR group . Restenosis “ catch-up ” was not found in our patient population Composite outcomes , in which multiple end points are combined , are frequently used as primary outcome measures in r and omized trials and are often associated with increased statistical efficiency . However , such measures may prove challenging for the interpretation of results . In this article , we examine the use of composite outcomes in major clinical trials , assess the arguments for and against them , and provide guidance on their application and reporting . To assess incidence and quality of reporting , we systematic ally review ed the use of composite end points in clinical trials in Annals of Internal Medicine , BMJ , Circulation , Clinical Infectious Diseases , Journal of the American College of Cardiology , JAMA , Lancet , New Engl and Journal of Medicine , and Stroke from 1997 through 2001 using a sensitive search strategy . We selected for review 167 original reports of r and omized trials ( with a total of 300 276 patients ) that included a composite primary outcome that incorporated all-cause mortality . Sixty-three trials ( 38 % ) were neutral both for the primary end point and the mortality component . Sixty trials ( 36 % ) reported significant results for the primary outcome measure but not for the mortality component . Only 6 trials ( 4 % ) were significant for the mortality component but not for the primary composite outcome , whereas 19 trials ( 11 % ) were significant for both . Twenty-two trials ( 13 % ) were inadequately reported . Our review suggests that reporting of composite outcomes is generally inadequate , implying that the results apply to the individual components of the composite outcome rather than only to the overall composite . Current guidelines for the undertaking and reporting of clinical trials could be revised to reflect the common use of composite outcomes in clinical trials BACKGROUND The placement of stents in coronary arteries has been shown to reduce restenosis in comparison to balloon angioplasty . However , clinical use of intracoronary stents is impeded by the risk of subacute stent thrombosis and complications associated with the anticoagulant regimen . To reduce these complications , the hypothesis that systemic anticoagulation is not necessary when adequate stent expansion is achieved was prospect ively evaluated on a consecutive series of patients who received intracoronary stents . METHODS AND RESULTS From March 1993 to January 1994 , 359 patients underwent Palmaz-Schatz coronary stent insertion . After an initial successful angiographic result with < 20 % stenosis by visual estimation had been achieved , intravascular ultrasound imaging was performed . Further balloon dilatation of the stent was guided by observation of the intravascular ultrasound images . All patients with adequate stent expansion confirmed by ultrasound were treated only with antiplatelet therapy ( either ticlopidine for 1 month with short-term aspirin for 5 days or only aspirin ) after the procedure . Clinical success ( procedure success without early postprocedural events ) at 2 months was achieved in 338 patients ( 94 % ) . With an inflation pressure of 14.9 + /- 3.0 atm and a balloon-to-vessel ratio of 1.17 + /- 0.19 , optimal stent expansion was achieved in 321 of the 334 patients ( 96 % ) who underwent intravascular ultrasound evaluation , with these patients receiving only antiplatelet therapy after the procedure . Despite the absence of anticoagulation , there were only two acute stent thromboses ( 0.6 % ) and one subacute stent thrombosis ( 0.3 % ) at 2-month clinical follow-up . Follow-up angiography at 3 to 6 months documented two additional occlusions ( 0.6 % ) at the stent site . At 6-month clinical follow-up , angiographically documented stent occlusion had occurred in 5 patients ( 1.6 % ) . At 6-month clinical follow-up , there was a 5.7 % incidence of myocardial infa rct ion , a 6.4 % rate of coronary bypass surgery , and a 1.9 % incidence of death . Emergency intervention ( emergency angioplasty or bailout stent ) for a stent thrombosis event was performed in 3 patients ( 0.8 % ) . The overall event rate was relatively high because of intraprocedural complications that occurred in 16 patients ( 4.5 % ) . Intraprocedural complications , however , decreased to 1 % when angiographically appropriately sized balloons were used for final stent dilations . There was one ischemic vascular complication that occurred at the time of the procedure and one ischemic vascular complication that occurred at the time of angiographic follow-up . By 6 months , repeat angioplasty for symptomatic restenosis was performed in 47 patients ( 13.1 % ) . CONCLUSIONS The Palmaz-Schatz stent can be safely inserted in coronary arteries without subsequent anticoagulation provided that stent expansion is adequate and there are no other flow-limiting lesions present . The use of high-pressure final balloon dilatations and confirmation of adequate stent expansion by intravascular ultrasound provide assurance that anticoagulation therapy can be safely omitted . This technique significantly reduces hospital time and vascular complications and has a low stent thrombosis rate Background —We have previously reported the safety and effectiveness of sirolimus-eluting stents for the treatment of de novo coronary lesions . The present investigation explored the potential of this technology to treat in-stent restenosis . Methods and Results —Twenty-five patients with in-stent restenosis were successfully treated with the implantation of 1 or 2 sirolimus-eluting Bx VELOCITY stents in São Paulo , Brazil . Nine patients received 2 stents ( 1.4 stents per lesion ) . Angiographic and volumetric intravascular ultrasound ( IVUS ) images were obtained after the procedure and at 4 and 12 months . All vessels were patent at the time of 12-month angiography . Angiographic late loss averaged 0.07±0.2 mm in-stent and −0.05±0.3 mm in-lesion at 4 months , and 0.36±0.46 mm in-stent and 0.16±0.42 mm in-lesion after 12 months . No patient had in-stent or stent margin restenosis at 4 months , and only one patient developed in-stent restenosis at 1-year follow-up . Intimal hyperplasia by 3-dimensional IVUS was 0.92±1.9 mm3 at 4 months and 2.55±4.9 mm3 after 1 year . Percent volume obstruction was 0.81±1.7 % and 1.76±3.4 % at the 4- and 12-month follow-up , respectively . There was no evidence of stent malapposition either acutely or in the follow-up IVUS images , and there were no deaths , stent thromboses , or repeat revascularizations . Conclusion —This study demonstrates the safety and the potential utility of sirolimus-eluting Bx VELOCITY stents for the treatment of in-stent restenosis Background —We have previously reported a virtual absence of neointimal hyperplasia 4 months after implantation of sirolimus-eluting stents . The aim of the present investigation was to determine whether these results are sustained over a period of 1 year . Methods and Results —Forty-five patients with de novo coronary disease were successfully treated with the implantation of a single sirolimus-eluting Bx VELOCITY stent in São Paulo , Brazil ( n=30 , 15 fast release [ group I , GI ] and 15 slow release [ GII ] ) and Rotterdam , The Netherl and s ( 15 slow release , GIII ) . Angiographic and volumetric intravascular ultrasound ( IVUS ) follow-up was obtained at 4 and 12 months ( GI and GII ) and 6 months ( GIII ) . In-stent minimal lumen diameter and percent diameter stenosis remained essentially unchanged in all groups ( at 12 months , GI and GII ; at 6 months , GIII ) . Follow-up in-lesion minimal lumen diameter was 2.28 mm ( GIII ) , 2.32 mm ( GI ) , and 2.48 mm ( GII ) . No patient approached the ≥50 % diameter stenosis at 1 year by angiography or IVUS assessment , and no edge restenosis was observed . Neointimal hyperplasia , as detected by IVUS , was virtually absent at 6 months ( 2±5 % obstruction volume , GIII ) and at 12 months ( GI=2±5 % and GII=2±3 % ) . Conclusions —This study demonstrates a sustained suppression of neointimal proliferation by sirolimus-eluting Bx VELOCITY stents 1 year after implantation Background —Early clinical studies demonstrated the feasibility of local paclitaxel delivery in reducing restenosis after treatment of de novo coronary lesions in small patient population s. Methods and Results —We conducted a r and omized , double-blind trial of 536 patients at 38 medical centers evaluating slow-release ( SR ) and moderate-release ( MR ) formulations of a polymer-based paclitaxel-eluting stent ( TAXUS ) for revascularization of single , primary lesions in native coronary arteries . Cohort I compared TAXUS-SR with control stents , and Cohort II compared TAXUS-MR with a second control group . The primary end point was 6-month percent in-stent net volume obstruction measured by intravascular ultrasound . Secondary end points were 6-month angiographic restenosis and 6- and 12-month inc Output:	At 12-month follow-up , sirolimus- or paclitaxel-eluting stents were effective and safe in patients with de novo lesions and low or medium risk of restenosis . At current market prices , the widespread use of these stents would involve an increase in health care expenditure for the different sensitivity scenarios we evaluated .
MS21397	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To describe posttraumatic growth ( PTG ) following childhood cancer survival and its association with demographic and disease/treatment variables , perceived treatment severity and life threat , and posttraumatic stress symptoms ( PTSS ) . METHOD Adolescent survivors of cancer ( N = 150 , ages 11 - 19 ) , at least 1 year after treatment , and their mothers ( N = 146 ) and fathers ( N = 107 ) completed self-report measures of perceived treatment intensity and PTSS and a semistructured interview design ed to identify posttraumatic responses and indicators of PTG including perceived positive changes for self , relationships , and life goals . RESULTS A majority of adolescents and their mothers and fathers reported PTG . Greater perceived treatment severity and life threat , but not objective disease severity , was associated with PTG . PTG and PTSS were positively associated for the adolescent cancer survivors . Diagnosis after age 5 result ed in more perceived benefit and greater PTSS for adolescent survivors . CONCLUSION Clarification of the concept and measurement of PTG after childhood cancer is warranted , as are prospect i ve studies of the association of PTG and PTSS and the role of demographic variables and illness-specific appraisal The correlates and consequences of benefit finding on quality of life were examined for 364 women ( 93 % Caucasian , 6 % African American , and 1 % Hispanic ) diagnosed with Stage I , II , and III breast cancer . Benefit finding and quality of life were measured 4 months postdiagnosis ( Tl ) , 3 months after Tl ( T2 ) , and 6 months after T2 ( T3 ) . Women with lower socioeconomic status , minorities , and those with more severe disease perceived more benefits at baseline . Benefit finding was associated with more negative affect at baseline and also interacted with stage of disease , such that negative relations to quality of life across time were limited to those with more severe disease . Findings suggest there are qualifiers as to whether " finding something good in the bad " is good or bad CONTEXT Adult survivors of childhood cancer are at risk for medical and psychosocial sequelae that may adversely affect their health status . OBJECTIVES To compare the health status of adult survivors of childhood cancer and siblings and to identify factors associated with adverse outcomes . DESIGN , SETTING , AND PARTICIPANTS Health status was assessed in 9535 adult participants of the Childhood Cancer Survivor Study , a cohort of long-term survivors of childhood cancer who were diagnosed between 1970 and 1986 . A r and omly selected cohort of the survivors ' siblings ( n = 2916 ) served as a comparison group . MAIN OUTCOME MEASURES Six health status domains were assessed : general health , mental health , functional status , activity limitations , cancer-related pain , and cancer-related anxiety/fears . The first 4 domains were assessed in the control group . RESULTS Survivors were significantly more likely to report adverse general health ( odds ratio [ OR ] , 2.5 ; 95 % confidence interval [ CI ] , 2.1 - 3.0 ; P<.001 ) , mental health ( OR , 1.8 ; 95 % CI , 1.6 - 2.1 ; P<.001 ) , activity limitations ( OR , 2.7 ; 95 % CI , 2.3 - 3.3 ; P<.001 ) , and functional impairment ( OR , 5.2 ; 95 % CI , 4.1 - 6.6 ; P<.001 ) , compared with siblings . Forty-four percent of survivors reported at least 1 adversely affected health status domain . Sociodemographic factors associated with reporting at least 1 adverse health status domain included being female ( OR , 1.4 ; 95 % CI , 1.3 - 1.6 ; P<.001 ) , lower level of educational attainment ( OR , 2.0 ; 95 % CI , 1.8 - 2.2 ; P<.001 ) , and annual income less than 20 000 dollars ( OR , 1.8 ; 95 % CI , 1.6 - 2.1 ; P<.001 ) . Relative to those survivors with childhood leukemia , an increased risk was observed for at least 1 adverse health status domain among those with bone tumors ( OR , 2.1 ; 95 % CI , 1.8 - 2.5 ; P<.001 ) , central nervous system tumors ( OR , 1.7 ; 95 % CI , 1.5 - 2.0 ; P<.001 ) , and sarcomas ( OR , 1.2 ; 95 % CI , 1.1 - 1.5 ; P = .01 ) . CONCLUSION Clinicians caring for adult survivors of childhood cancer should be aware of the substantial risk for adverse health status , especially among females , those with low educational attainment , and those with low household incomes OBJECTIVE In order to broaden the view beyond posttraumatic stress disorder ( PTSD ) in children , we examined to what extent posttraumatic stress reactions , posttraumatic growth , and quality of life were related to each other and to traumatic exposure in the general population . METHOD 1770 children of 36 r and omly selected primary schools ( mean age = 10.24 years , 50 % boys ) reported in October/November 2006 on their worst experience ( traumatic exposure was considered present when the described event fulfilled the A1 criterion for PTSD of the DSM-IV-TR ) and filled out the Children 's Responses to Trauma Inventory , the Posttraumatic Growth Inventory for Children , and the KIDSCREEN-27 . Correlational and hierarchical linear regression analyses were carried out in a multiple imputation format . RESULTS Posttraumatic stress reactions were strongly related to posttraumatic growth ( r = 0.41 , p < .01 ) and quality of life ( r = -0.47 , p < .01 ) . The latter 2 variables were weakly related ; positively when controlling for posttraumatic stress reactions ( r = 0.09 , p < .01 ) , negatively when not ( r = -0.12 , p < .01 ) . Children who were exposed to trauma reported more posttraumatic stress reactions ( β = .12 , p < .01 ) , more posttraumatic growth ( β = .09 , p < .01 ) , and less quality of life ( β = -.08 , p < .01 ) than nonexposed children ( effect sizes were small ) . CONCLUSIONS Negative and positive psychological sequelae of trauma can coexist in children , and extend to broader areas of life than specific symptoms only . Clinicians should look further than PTSD alone and pay attention to the broad range of posttraumatic stress reactions that children show , their experience of posttraumatic growth , and their quality of life Psychological reactions to having had childhood cancer often continue after treatment ends , for survivors and their parents . Based on our previous research , we developed an intervention program for adolescent survivors of childhood cancer , their parents , and siblings . Surviving Cancer Competently : An Intervention Program -- SCCIP -- is a one-day family group intervention that combines cognitive-behavioral and family therapy approaches . The goals of SCCIP are to reduce symptoms of distress and to improve family functioning and development . SCCIP is described and data from a pilot study of 19 families are presented . Program evaluation data indicated that all family members found SCCIP helpful . St and ardized measures administered before the intervention and again at 6 months after SCCIP showed that symptoms of posttraumatic stress and anxiety decreased . Changes in family functioning were more difficult to discern . Overall , the results were promising with regard to the feasibility of the program and its potential for reducing symptoms of distress for all family members Output:	Several findings were consistent with a comparable meta- analysis in adult oncology population s. Targeted social support , clinical intervention , and education may facilitate post-traumatic growth .
MS21398	*TASK* the task is to summarize an input biomedical literature in six sentences *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 address the lack of a simple and st and ardized instrument to assess overall panic disorder severity , the authors developed a scale for the measurement of panic disorder severity . METHOD Ten independent evaluators used the seven-item Panic Disorder Severity Scale to assess 186 patients with principal DSM-III-R diagnoses of panic disorder ( with no or mild agoraphobia ) who were participating in the Multicenter Collaborative Treatment Study of Panic Disorder . In addition , 89 of these patients were reevaluated with the same scale after short-term treatment . A subset of 24 patients underwent two independent assessment s to establish interrater reliability . Internal consistency , convergent and discriminant validity , and sensitivity to change were also determined . RESULTS The Panic Disorder Severity Scale was associated with excellent interrater reliability , moderate internal consistency , and favorable levels of validity and sensitivity to change . Individual items showed good convergent and discriminant validity . Analysis suggested a two-factor model fit the data best . CONCLUSIONS The Panic Disorder Severity Scale is a simple , efficient way for clinicians to rate severity in patients with established diagnoses of panic disorder . However , further research with more diverse groups of panic disorder patients and with a broader range of convergent and discriminant validity measures is needed OBJECTIVE Recent studies have suggested that most patients treated for panic disorder receive forms of psychotherapy other than cognitive behavior therapy , even though there is little information about the efficacy of such treatments or how they compare to proven active treatments . The authors compared one of these other forms , emotion-focused psychotherapy ( given to 30 patients with panic disorder ) , to results obtained with recommended st and ard treatment ( either cognitive behavior therapy [ N=36 ] or imipramine [ N=22 ] ) . The authors also compared emotion-focused psychotherapy to results obtained in subjects given pill placebo ( N=24 ) . METHOD Subjects met DSM-IV criteria for panic disorder with no more than mild agoraphobia . Treatment consisted of approximately 3 months of weekly visits followed by 6 monthly maintenance visits . Assessment s were conducted after each treatment phase and at a follow-up visit after 6 months of no treatment . RESULTS Emotion-focused psychotherapy was less effective for symptoms of panic disorder than treatment with either cognitive behavior therapy or imipramine ; results obtained with emotion-focused psychotherapy after the acute and maintenance phases were similar to those seen with placebo . Treatment expectations were not different among the different groups . Patients receiving emotion-focused psychotherapy had the highest completion rate . CONCLUSIONS The results suggest that emotion-focused psychotherapy ( a supportive form of psychotherapy ) has low efficacy for the treatment of panic disorder . However , emotion-focused psychotherapy may be superior to medical management in helping patients stay in treatment CONTEXT Panic disorder ( PD ) may be treated with drugs , psychosocial intervention , or both , but the relative and combined efficacies have not been evaluated in an unbiased fashion . OBJECTIVE To evaluate whether drug and psychosocial therapies for PD are each more effective than placebo , whether one treatment is more effective than the other , and whether combined therapy is more effective than either therapy alone . DESIGN AND SETTING R and omized , double-blind , placebo-controlled clinical trial conducted in 4 anxiety research clinics from May 1991 to April 1998 . PATIENTS A total of 312 patients with PD were included in the analysis . INTERVENTIONS Patients were r and omly assigned to receive imipramine , up to 300 mg/d , only ( n=83 ) ; cognitive-behavioral therapy ( CBT ) only ( n=77 ) ; placebo only ( n=24 ) ; CBT plus imipramine ( n=65 ) ; or CBT plus placebo ( n=63 ) . Patients were treated weekly for 3 months ( acute phase ) ; responders were then seen monthly for 6 months ( maintenance phase ) and then followed up for 6 months after treatment discontinuation . MAIN OUTCOME MEASURES Treatment response based on the Panic Disorder Severity Scale ( PDSS ) and the Clinical Global Impression Scale ( CGI ) by treatment group . RESULTS Both imipramine and CBT were significantly superior to placebo for the acute treatment phase as assessed by the PDSS ( response rates for the intent-to-treat [ ITT ] analysis , 45.8 % , 48.7 % , and 21.7 % ; P=.05 and P=.03 , respectively ) , but were not significantly different for the CGI ( 48 . 2 % , 53.9 % , and 37.5 % , respectively ) . After 6 months of maintenance , imipramine and CBT were significantly more effective than placebo for both the PDSS ( response rates , 37.8 % , 39.5 % , and 13.0 % , respectively ; P=.02 for both ) and the CGI ( 37.8 % , 42.1 % , and 13.0 % , respectively ) . Among responders , imipramine produced a response of higher quality . The acute response rate for the combined treatment was 60.3 % for the PDSS and 64.1 % for the CGI ; neither was significantly different from the other groups . The 6-month maintenance response rate for combined therapy was 57.1 % for the PDSS ( P=.04 vs CBT alone and P=.03 vs imipramine alone ) and 56.3 % for the CGI ( P=.03 vs imipramine alone ) , but not significantly better than CBT plus placebo in either analysis . Six months after treatment discontinuation , in the ITT analysis CGI response rates were 41.0 % for CBT plus placebo , 31.9 % for CBT alone , 19.7 % for imipramine alone , 13 % for placebo , and 26.3 % for CBT combined with imipramine . CONCLUSIONS Combining imipramine and CBT appeared to confer limited advantage acutely but more substantial advantage by the end of maintenance . Each treatment worked well immediately following treatment and during maintenance ; CBT appeared durable in follow-up . JAMA . 2000;283:2529 - OBJECTIVE The purpose of this comparative outcome study was to investigate whether the effects of exposure in vivo treatment for panic disorder with agoraphobia could be enhanced by adding interventions specifically for panic attacks before the start of exposure treatment . The additional effect of two types of treatment for panic attacks -- pharmacological ( fluvoxamine ) and psychological ( repeated hyperventilation provocations and respiratory training)--was examined . Thus , the combined treatment of panic interventions with exposure in vivo could be compared to exposure in vivo alone . METHOD Ninety-six patients were r and omly assigned to four treatment conditions : double-blind , placebo-controlled fluvoxamine followed by exposure in vivo , psychological panic management followed by exposure , and exposure in vivo alone . Outcome was assessed by self-report measures , a st and ardized multitask behavioral avoidance test , and continuous monitoring of panic attacks . Seventy-six patients completed the study . RESULTS All four treatments were effective and result ed in a significant decrease of agoraphobic avoidance . Moreover , the combination of fluvoxamine and exposure in vivo demonstrated efficacy superior to that of the other treatments and had twice as large an effect size ( difference between pre- and posttreatment scores ) on self-reported agoraphobic avoidance . The other treatments did not differ among each other in effectiveness . CONCLUSIONS Results of the study indicate that the short-term outcome of exposure in vivo treatment can be enhanced by adding fluvoxamine treatment . Psychological panic management combined with exposure was not superior to exposure alone of equal duration Output:	Conclusion The act of taking a pill placebo may enhance the placebo effect already contained in the effective psychotherapeutic intervention during the acute phase treatment . Theoretically this is an argument against the recently cl aim ed null hypothesis of placebo effect in general and clinical ly it may point to some further room for enhancing the psychotherapeutic approach for panic disorder
MS21399	*TASK* the task is to summarize an input biomedical literature in six sentences *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 high platelet turnover rate produce a population of immature reticulated platelets ( RP ) that could confer , despite of antiplatelet drugs , a residual platelet reactivity ( RPR ) in coronary artery disease ( CAD ) patients . To assess the influence of RP on platelet reactivity in CAD patients on dual antiplatelet therapy we measured RP in 372 patients by using the Sysmex XE-2100 haematology analyzer and platelet function by optical platelet aggregometry ( PA ) on platelet-rich-plasma induced by 1 mmol arachidonic acid ( AA-PA ) and 10 microM ADP ( ADP-PA ) . RPR was defined as either AA-PA>20 % or ADP-PA>70 % . RP were expressed as a percentage of RP of the total optical platelet count ( immature platelet fraction ; IPF ) and as the percentage of RP highly fluorescent ( highly fluorescent immature platelet fraction ; H-IPF ) . Moderate but significant positive correlations between PA , IPF , H-IPF , and mean platelet volume ( MPV ) were found . According to tertiles of IPF , H-IPF and MPV , a significant trend for an increase of platelet aggregation by AA and ADP was evidence d. Furthermore , a significant difference for IPF , H-IPF and MPV between patients with and without RPR was observed . A linear regression analysis showed that IPF , H-IPF and MPV significantly affected PA measured by AA and ADP . At multivariate linear regression analysis these associations were confirmed . Moreover , a logistic regression analysis demonstrated that IPF , H-IPF and MPV significantly influenced the risk of RPR , and in the multivariate model these results remained significant . This study indicates that a high rate of platelet turnover is a new mechanism associated with platelet reactivity in high risk CAD patients on dual antiplatelet therapy BACKGROUND Mean platelet volume ( MPV ) is a strong predictor of impaired angiographic reperfusion and 6-month mortality in ST-elevation myocardial infa rct ion ( MI ) treated with primary percutaneous coronary intervention ( PCI ) . No data is available for other platelet volume indices : platelet distribution width ( PDW ) and platelet large cell ratio ( P-LCR ) . The aim was to assess the impact of 3 platelet volume indices on long-term prognosis in patients treated with primary PCI in acute MI . METHODS This prospect i ve study enrolled 538 patients who underwent primary PCI in acute MI . Admission blood sample s were measured for MPV , PDW , and P-LCR . The patients were followed-up a mean period of 26 ± 11 months with regard to cardiac death , non-fatal reinfa rct ion , re-PCI or coronary artery bypass grafting . RESULTS Kaplan-Meier survival analysis showed a significantly higher 26-month mortalityrate in patients with high MPV ( ≥ 11.7 fL ) than in those with low MPV ( < 11.7 fL ) ( 14.6 % vs. 5.5 % , p = 0.0008 ) . Similar findings were related to high P-LCR ( ≥ 38.1 % ) vs. low P-LCR ( < 38.1 % ) - mortality 13.8 % vs. 5.8 % , p = 0.0025 . Higher PDW values ( ≥ 16 fL ) correlated with higher mortality rate as compared to PDW < 16 fL ( 17.4 % vs. 6.3 % , p = 0.0012 ) . PDW was found to be an independent prognostic factor for cardiac mortality and composite endpoint . CONCLUSIONS Mean platelet volume , platelet distribution width and platelet large cell ratio measured on admission are strong , independent prognostic factors in PCI-treated acute MI CONTEXT Patients with unstable angina/non-ST-segment elevation myocardial infa rct ion ( MI ) ( UA/NSTEMI ) present with a wide spectrum of risk for death and cardiac ischemic events . OBJECTIVE To develop a simple risk score that has broad applicability , is easily calculated at patient presentation , does not require a computer , and identifies patients with different responses to treatments for UA/NSTEMI . DESIGN , SETTING , AND PATIENTS Two phase 3 , international , r and omized , double-blind trials ( the Thrombolysis in Myocardial Infa rct ion [ TIMI ] 11B trial [ August 1996-March 1998 ] and the Efficacy and Safety of Subcutaneous Enoxaparin in Unstable Angina and Non-Q-Wave MI trial [ ESSENCE ; October 1994-May 1996 ] ) . A total of 1957 patients with UA/NSTEMI were assigned to receive unfractionated heparin ( test cohort ) and 1953 to receive enoxaparin in TIMI 11B ; 1564 and 1607 were assigned respectively in ESSENCE . The 3 validation cohorts were the unfractionated heparin group from ESSENCE and both enoxaparin groups . MAIN OUTCOME MEASURES The TIMI risk score was derived in the test cohort by selection of independent prognostic variables using multivariate logistic regression , assignment of value of 1 when a factor was present and 0 when it was absent , and summing the number of factors present to categorize patients into risk strata . Relative differences in response to therapeutic interventions were determined by comparing the slopes of the rates of events with increasing score in treatment groups and by testing for an interaction between risk score and treatment . Outcomes were TIMI risk score for developing at least 1 component of the primary end point ( all-cause mortality , new or recurrent MI , or severe recurrent ischemia requiring urgent revascularization ) through 14 days after r and omization . RESULTS The 7 TIMI risk score predictor variables were age 65 years or older , at least 3 risk factors for coronary artery disease , prior coronary stenosis of 50 % or more , ST-segment deviation on electrocardiogram at presentation , at least 2 anginal events in prior 24 hours , use of aspirin in prior 7 days , and elevated serum cardiac markers . Event rates increased significantly as the TIMI risk score increased in the test cohort in TIMI 11B : 4.7 % for a score of 0/1 ; 8.3 % for 2 ; 13 . 2 % for 3 ; 19.9 % for 4 ; 26.2 % for 5 ; and 40.9 % for 6/7 ( P<.001 by chi(2 ) for trend ) . The pattern of increasing event rates with increasing TIMI risk score was confirmed in all 3 validation groups ( P<.001 ) . The slope of the increase in event rates with increasing numbers of risk factors was significantly lower in the enoxaparin groups in both TIMI 11B ( P = .01 ) and ESSENCE ( P = .03 ) and there was a significant interaction between TIMI risk score and treatment ( P = . 02 ) . CONCLUSIONS In patients with UA/NSTEMI , the TIMI risk score is a simple prognostication scheme that categorizes a patient 's risk of death and ischemic events and provides a basis for therapeutic decision making . JAMA . 2000;284:835 - Data from the Diet and Reinfa rct ion Trial were examined to check the prognostic effects of plasma fibrinogen , plasma viscosity , white blood cell count , haemoglobin and mean platelet volume in 92 deaths among 1755 men who had recently recovered from acute myocardial infa rct ion . All these variables were significantly associated with all-cause mortality over the following 18 months ( haemoglobin negatively , the others positively ) . Those who gave up smoking following their infa rct had a lower mortality than those who continued to smoke ( 4.1 % and 7.9 % respectively ) , and this effect appeared to be mediated by fibrinogen levels . Smoking habit accounted for only part of the prognostic effect of fibrinogen and white blood cell count . Haematological variables have an important prognostic significance after myocardial infa rct ion . Cessation of smoking after myocardial infa rct ion is worthwhile and has a favourable effect on plasma fibrinogen Mean platelet volume ( MPV ) has been proposed as a marker of platelet reactivity and cardiovascular risk . Its prognostic significance has not been thoroughly investigated in patients with non-ST elevation acute coronary syndrome ( NSTE-ACS ) . We included 1,041 consecutive patients with NSTE-ACS . Patients were divided in quartiles according to the MPV value on admission ( fl ) i.e. Q1<7.5 ; Q2=7.5 - 8.0 ; Q3=8.1 - 8.8 ; Q4≥8.9 . The primary study endpoint was the composite of cardiovascular death and re-myocardial infa rct ion ( MI ) at one year . Secondary study endpoints were individual cardiovascular death and re-MI . Patients in Q4 were older , had a higher prevalence of previous MI , peripheral artery disease and advanced Killip class compared to patients in Q1-Q3 . Elevated MPV levels ( Q4 ) was independently associated with gender , smoking status , platelet count and creatinine level . Overall , 210 patients ( 20.2 % ) reached the primary endpoint , 124 ( 12.1 % ) died from cardiovascular causes and 125 ( 12.0 % ) suffered from re-MI . On multivariable analysis patients in Q4 were at higher risk of primary endpoint ( HR=1.41 ; 95%CI 1.06 - 1.89 ; p=0.02 ) whilst the association with cardiovascular death and re-MI was attenuated . MPV as continuous variable was independently associated with both primary endpoint ( HR=1.19 ; 95%CI 1.06 - 1.33 ; p=0.003 ) and cardiovascular death ( HR=1.23 ; 95%CI 1.06 - 1.42 , p=0.006 ) . The incorporation of MPV into a comprehensive model of risk significantly increased the likelihood ratio chi-square for prediction of both the composite endpoint ( p=0.004 ) and cardiovascular death ( p=0.009 ) . Therefore , MPV may be useful to improve risk stratification in NSTE-ACS patients and should be included in future prospect i ve studies evaluating the role of platelet function in promoting cardiovascular events BACKGROUND Appropriate treatment policies should include an accurate estimate of a patient 's baseline risk . Risk modeling to date has been underutilized in patients with acute coronary syndromes without persistent ST-segment elevation . METHODS AND RESULTS We analyzed the relation between baseline characteristics and the 30-day incidence of death and the composite of death or myocardial (re)infa rct ion in 9461 patients with acute coronary syndromes without persistent ST-segment elevation enrolled in the PURSUIT trial [ Platelet glycoprotein IIb/IIIa in Unstable angina : Receptor Suppression Using Integrilin ( eptifibatide ) Therapy ] . Variables examined included demographics , history , hemodynamic condition , and symptom duration . Risk models were created with multivariable logistic regression and vali date d by bootstrapping techniques . There was a 3.6 % mortality rate and 11.4 % infa rct ion rate by 30 days . More than 20 significant predictors for mortality and for the composite end point were identified . The most important baseline determinants of death were age ( adjusted chi(2)=95 ) , heart rate ( chi(2)=32 ) , systolic blood pressure ( chi(2)=20 ) , ST-segment depression ( chi(2)=20 ) , signs of heart failure ( chi(2)=18 ) , and cardiac enzymes ( chi(2)=15 ) . Determinants of mortality were generally also predictive of death or myocardial (re)infa rct ion . Differences were observed , however , in the relative prognostic importance of predictive variables for mortality alone or the composite end point ; for example , sex was a more important determinant of the composite end point ( chi(2)=21 ) than of death alone ( chi(2)=10 ) . The accuracy of the prediction of the composite end point was less than that of mortality ( C-index 0.67 versus 0.81 ) . CONCLUSIONS The occurrence of adverse events after presentation with acute coronary syndromes is affected by multiple factors . These factors should be considered in the clinical decision-making process A prospect i ve study was performed to investigate the role of the endogenous fibrinolytic system and platelet function for the occurrence of reocclusion after successful recanalization of chronic coronary occlusions . At control coronary angiography 8 + /- 2 weeks after recanalization , reocclusion was found in 10 ( 21 % ) of 47 patients . After correction for angiographic and clinical confounding factors , endogenous concentrations of tissue plasminogen activator ( TPA ) were lower in patients with reocclusion than in patients without . In contrast , plasma levels of plasminogen activator inhibitor-1 and alpha 2-antiplasmin were similar in the two groups . The mean platelet volume was significantly higher in patients with reocclusion than in patients without . In addition , agonist-induced platelet aggregation in platelet-rich plasma was enhanced in the patients with reocclusion . Decreased endogenous plasma TPA concentrations and enhanced platelet reactivity may contribute to the occurrence of reocclusion after primarily successful coronary artery recanalization Mean platelet volume ( MPV ) is a value that is available from st and ard blood count . Increased Output:	These findings suggest that MPV may be a useful prognostic marker in patients with CAD

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