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MS21200	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Norfolk Quality of Life Question naire-Diabetic Neuropathy ( Norfolk QOL-DN ) is a vali date d comprehensive question naire design ed to capture the entire spectrum of DN related to large fiber , small fiber , and autonomic neuropathy not captured in existing instruments . We aim ed to determine if the Norfolk QOL-DN could be used to capture changes in QOL that correlate with nerve fiber-specific objective measures in a placebo-controlled trial of two agents that affect different nerve fibers . Methods : Sixty patients with DN were allocated to treatment on ruboxistaurin ( RBX ) ( n = 18 ) , topiramate ( TPX ) ( n = 18 ) , or placebo ( n = 18 ) . QOL-DN was administered and objective measures of nerve function were performed at entry and end of the study period . Results : Total QOL scores improved significantly in the active treatment groups ( RBX −9.56 ± 4.13 ; TPX −12.22 ± 2.76 ) but not in placebo ( −5.56 ± 3.49 ) . There were differences in nerve function improvement between treatments . Neurological symptom scores ( NSS ) improved with TPX from 5.5 ( 2.3 ) to 4.3 ( 0.65 ) ( p = .007 ) , sensory scores improved with TPX from 15.5 ( 1.79 ) to 8.3 ( 1.19 ) ( p < .001 ) , motor scores did not change , and sensory and motor impairment scores improved with TPX from 18.8 ( 2.15 ) to 12.1 ( 1.71 ) ( p = .003 ) . Total neuropathy scores ( TNS ) improved with TPX from 24.35 ( 2.61 ) to 16.35 ( 2.02 ) ( p = .001 ) . Neuropathy total symptom score−6 ( NTSS−6 ) changes were significant for both treatments : RBX 4.38 ( 0.75 ) to 1.49 ( 0.38 ) ( p < .001 ) and TPX 7.57 ( 1.3 ) to 4.26 ( 0.95 ) ( p = .036 ) . Changes in QOL-DN large fiber subscores correlated ( Spearman 's rank ) significantly with changes in NTSS-6 ( r = 0.55 ; p < .0001 ) , NSS ( r = 0.31 ; p < .04 ) , neuropathy impairment score ( NIS ) ( r = 0.35 ; p < .02 ) , and TNS ( r = 0.48 ; p < .0006 ) . Changes in QOL-DN small fiber subscores correlated significantly with changes in NTSS-6 total scores ( r = 0.40 ; p < .005 ) and intraepidermal nerve fiber density ( IENFD ) ( r = −0.29 ; p < .05 ) . Conclusion : Ruboxistaurin produced significant improvement in large fiber measures while TPX produced significant changes in small fiber measures . The Norfolk QOL-DN tool differentiated between these changes captured in the fiber-specific domains . Correlations were found between objective measures of neuropathy and total QOL , but those with nerve fiber domain scores were modest and reinforce the need to quantify QOL as an endpoint in neuropathy independent of other measures Background / Aims : Bardoxolone methyl , a novel synthetic triterpenoid , induces Nrf2 , a transcription factor known to play a key role in decreasing oxidative stress and the production of pro-inflammatory molecules . Methods : This exploratory multi-center , open-label study assessed the clinical activity and safety of bardoxolone methyl in 20 patients with moderate to severe chronic kidney disease and type 2 diabetes . Patients received 25 mg of bardoxolone methyl daily for 28 days , followed by 75 mg daily for another 28 days . Results : The study achieved its primary efficacy endpoint , as demonstrated by a significant increase from baseline in estimated glomerular filtration rate ( eGFR ) of 7.2 ml/min/1.73 m2 ( p < 0.001 ) . Improvements were seen in approximately 90 % of patients and showed a dose- and time-dependent increase in eGFR . The eGFR change paralleled a significant reduction in serum creatinine ( –0.3 mg/dl ) and blood urea nitrogen ( –4.9 mg/dl ) , along with an increase in creatinine clearance ( + 14.6 ml/min/1.73 m2 ) , without a change in the 24-hour creatinine excretion rate . Markers of vascular injury and inflammation were improved by treatment with bardoxolone . No life-threatening adverse events or drug-related serious adverse events were reported . Conclusions : The results describe an apparent increase in kidney function following relatively short-term treatment with bardoxolone methyl , a promising new agent that warrants placebo-controlled studies to define its long-term effects on renal function Prior research has shown that in experimental diabetes mellitus , green tea reduces albuminuria by decreasing podocyte apoptosis through activation of the WNT pathway . We investigated the effect of green tea polyphenols ( GTP ) on residual albuminuria of diabetic subjects with nephropathy . We conducted a r and omised , double-blind study in 42 diabetic subjects with a urinary albumin-creatinine ratio ( UACR ) > 30 mg/g , despite administration of the maximum recommended dose of renin-angiotensin ( RAS ) inhibition . Patients were r and omly assigned to two equal groups to receive either GTP ( containing 800 mg of epigallocatechin gallate , 17 with type 2 diabetes and 4 with type 1 diabetes ) or placebo ( 21 with type 2 diabetes ) for 12 weeks . Treatment with GTP reduced UACR by 41 % , while the placebo group saw a 2 % increase in UACR ( p = 0.019 ) . Podocyte apoptosis ( p = 0.001 ) and in vitro albumin permeability ( p < 0.001 ) were higher in immortalized human podocytes exposed to plasma from diabetic subjects compared to podocytes treated with plasma from normal individuals . In conclusion , GTP administration reduces albuminuria in diabetic patients receiving the maximum recommended dose of RAS . Reduction in podocyte apoptosis by activation of the WNT pathway may have contributed to this effect Background / Aims : Treatments of diabetic nephropathy ( DN ) delay the onset of end-stage renal disease . We report the results of safety/tolerability studies in patients with overt nephropathy and type 1/type 2 diabetes treated with pyridoxamine , a broad inhibitor of advanced glycation . Methods : The two 24-week studies were multicenter Phase 2 trials in patients under st and ard-of-care . In PYR-206 , patients were r and omized 1:1 and had baseline serum creatinine ( bSCr ) ≤2.0 mg/dl . In PYR-205/207 , r and omization was 2:1 and bSCr was ≤2.0 for PYR-205 and ≧2.0 but ≤3.5 mg/dl for PYR-207 . Treated patients ( 122 active , 90 placebo ) received 50 mg pyridoxamine twice daily in PYR-206 ; PYR-205/207 patients were escalated to 250 mg twice daily . Results : Adverse events were balanced between the groups ( p = NS ) . Slight imbalances , mainly in the PYR-205/207 groups , were noted in deaths ( from diverse causes , p = NS ) and serious adverse events ( p = 0.05 ) that were attributed to pre-existing conditions . In a merged data set , pyridoxamine significantly reduced the change from baseline in serum creatinine ( p < 0.03 ) . In patients similar to the RENAAL/IDNT studies ( bSCr ≧1.3 mg/dl , type 2 diabetes ) , a treatment effect was observed on the rise in serum creatinine ( p = 0.007 ) . No differences in urinary albumin excretion were seen . Urinary TGF-β1 also tended to decrease with pyridoxamine ( p = 0.049 ) as did the CML and CEL AGEs . Conclusion : These data provide a foundation for further evaluation of this AGE inhibitor in DN Inflammation is a central component of progressive chronic kidney disease ( CKD ) . Iron promotes oxidative stress and inflammatory response in animals and promotes progressive CKD . Parenteral iron provokes oxidative stress in patients with CKD ; however , its potential to provoke an inflammatory response is unknown . In 20 veterans with CKD , 100 mg iron sucrose was administered intravenously over 5 min and urinary excretion rate and plasma concentration of monocyte chemoattractant protein-1 ( MCP-1 ) were measured at timed intervals over 24 h. Patients were then r and omized to placebo or N-acetyl cysteine ( NAC ) 600 mg b.i.d . and the experiment was repeated at 1 week . Iron sucrose markedly increased plasma concentration and urinary excretion rate of MCP-1 at baseline and at 1 week visits ( P < 0.0001 for time effect ) . Urinary excretion peaked at 30 min and plasma concentration at 15 min . Plasma MCP-1 concentration fell from 164 + /- 17.7 to 135 + /- 17.7 pg/ml with NAC , whereas it remained unchanged from 133 + /- 12.5 to 132 + /- 17.7 pg/ml with placebo ( P=0.001 for visit x antioxidant drug interaction ) . There was a reduction in MCP-1 urinary excretion rate from visit 1 to 2 . At the baseline visit , the urinary excretion rate averaged 305 + /- 66 pg/min and at the second visit 245 + /- 67 pg/min ( mean difference 60 + /- 28 pg/min , P = 0.030 ) . There was no improvement in urinary MCP-1 excretion with NAC . In conclusion , iron sucrose causes rapid and transient generation and /or release of MCP-1 plasma concentration and increases urinary excretion rate , and systemic MCP-1 level but the urinary excretion rate is not abrogated with the antioxidant NAC . These results may have implication s for the progression of CKD with parenteral iron Background Arterial stiffness is increased in patients with CKD and is a powerful predictor of cardiovascular morbidity and mortality . Use of the xanthine oxidase inhibitor allopurinol has been shown to improve endothelial function , reduce left ventricular hypertrophy and possibly improve cardiovascular outcome . We explored the relationship between use of allopurinol and arterial stiffness in patients with chronic kidney disease ( CKD ) . Methods Cross-sectional observational study of 422 patients with CKD with evidence of , or at high risk of , renal disease progression . Arterial stiffness was determined by carotid-femoral pulse wave velocity ( PWV ) . Results The mean age was 63±16 years , median estimated glomerular filtration rate was 25 ( interquartile range : 19–31 ) ml/min/1.73 m2 and mean PWV was 10.2±2.4 m/s . Seventy-seven patients ( 18 % ) were receiving regular allopurinol , 61 % at a dose of 100 mg/day ( range : 50–400 mg/day ) . Patients receiving allopurinol had significantly lower peripheral pulse pressure , central pulse pressure , central systolic blood pressure , serum uric acid level tissue advanced glycation end product levels but comparable high-sensitivity C-reactive protein levels . Use of allopurinol was associated with lower PWV . After adjusting for age , gender , ethnicity , tissue advanced glycation end product level , peripheral pulse pressure , smoking pack years , presence of diabetes mellitus and use of angiotensin converting enzyme inhibitor or angiotensin II receptor blocker , the use of allopurinol remained a significant independent determinant of PWV ( mean difference : −0.63 m/s ; 95 % CI , −0.09 to −1.17 m/s , p = 0.02 ) . Conclusion In patients with CKD , use of allopurinol is independently associated with lower arterial stiffness . This study provides further justification for a large definitive r and omised controlled trial examining the therapeutic potential of allopurinol to reduce cardiovascular risk in people with CKD Pyridoxamine dihydrochloride ( Pyridorin , NephroGenex ) inhibits formation of advanced glycation end products and scavenges reactive oxygen species and toxic carbonyls , but whether these actions translate into renoprotective effects is unknown . In this double-blind , r and omized , placebo-controlled trial , we r and omly assigned 317 patients with proteinuric type 2 diabetic nephropathy to twice-daily placebo ; Py Output:	The findings of this investigation indicate that antioxidant treatment is effective clinical ly for DN treatment in T2DM patient .
MS21201	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVES The aim of the present case series was to evaluate the 2-year results obtained following treatment of peri-implantitis lesions using either a nanocrystalline hydroxyapatite ( NHA ) or a natural bone mineral in combination with a collagen membrane ( NBM+CM ) . MATERIAL AND METHODS Twenty-two patients suffering from moderate peri-implantitis ( n=22 intra-bony defects ) were r and omly treated with ( i ) access flap surgery ( AFS ) and the application of NHA , or with AFS and the application of NBM+CM . Clinical parameters were recorded at baseline and after 12 , 18 , and 24 months of non-submerged healing . RESULTS Two patients from the NHA group were excluded from the study due to severe pus formation at 12 months . At 24 months , both groups revealed clinical ly important probing depth ( PD ) reductions ( NHA : 1.5+/-0.6 mm ; NBM+CM : 2.4+/-0.8 mm ) and clinical attachment level ( CAL ) gains ( NHA : 1.0+/-0.4 mm ; NBM+CM : 2.0+/-0.8 mm ) . However , these clinical improvements seemed to be better in the NBM+CM group ( difference between groups : PD reduction : 0.9+/-0.2 mm ; CAL gain : 1.0+/-0.3 mm ) . CONCLUSION Both treatment procedures have shown efficacy over a period of 24 months , however , the application of NBM+CM may result in an improved outcome of healing AIM This r and omized clinical trial presents a 12-month follow-up of the clinical and microbiological results after application of minocycline microspheres as an adjunct to mechanical treatment of incipient peri-implant infections compared with an adjunctive treatment using 1 % chlorhexidine gel application . MATERIAL AND METHODS Thirty-two subjects with probing depth > or = 4 mm , combined with bleeding and /or exu date on probing and presence of putative pathogenic bacteria were given oral hygiene instructions and mechanical treatment of infected areas adjacent to implants . The subjects were then r and omly assigned adjunctive subgingival antimicrobial treatment using either chlorhexidine gel or minocycline microspheres . Sixteen patients in the minocycline group and 14 in the chlorhexidine group completed the study . Follow-up examinations were carried out after 10 days , 1 , 2 , 3 , 6 , 9 and 12 months . RESULTS The adjunctive use of minocycline microspheres result ed in improvements of probing depths and bleeding scores , whereas the adjunctive use of chlorhexidine only result ed in limited reduction of bleeding scores . For the deepest sites of the treated implants in the minocycline group , the mean probing depth was reduced from 5.0 to 4.4 mm at 12 months . This study could not show any significant difference in the levels of bacterial species or groups at any time point between the two antimicrobial agents tested . The present findings encourage further studies on adjunctive use of minocycline microspheres in the treatment of peri-implant lesions . CONCLUSIONS The use of a local antibiotic as an adjunct to mechanical treatment of incipient peri-implantitis lesions demonstrated improvements in probing depths that were sustained over 12 months This report presents the clinical results three months after application of minocycline microspheres as an adjunct to mechanical treatment of incipient peri-implant infections compared to adjunctive treatment employing 1 % chlorhexidine gel application . Sixteen patients in the minocycline group and 14 in the chlorhexidine group completed the study . Each patient had one or more implants with probing depth > or = 4 mm combined with bleeding and /or exu date on probing and presence of putative pathogenic bacteria . At baseline , patients were r and omly assigned to minocycline or chlorhexidine treatment . Follow-up examinations were carried out after 10 , 30 , 60 and 90 days . The combined mechanical/antimicrobial treatment for the chlorhexidine group did not result in any reduction in probing depth and only limited reduction of bleeding scores . The adjunctive use of minocycline microspheres , on the other h and , result ed in improvements in both probing depths and bleeding scores . For the deepest sites of the treated implants , mean probing depth was reduced from 5.0 mm to 4.1 mm . The reductions in bleeding scores , although greater than for the chlorhexidine group , were modest . Thus , the question as to what extent the combined mechanical/minocycline treatment could be considered adequate for the treated lesions remains to be answered . The present short-term findings , however , encourage further studies with longer observation intervals on adjunctive use of minocycline microspheres in the treatment of periimplant lesions & NA ; Between 1994 and 1999 , 50 patients were treated with either profound parodontopathy ( 30 ) or periimplantitis ( 20 ) . Half of each of the two groups of patients was treated conventionally , and the other half was treated with laser support . Before the operation , microbiological examinations were carried out , in addition to registering the clinical findings and taking x‐rays . These procedures were repeated after the operation , and again after 6 , 12 , 24 , 36 , 48 , and 60 months . The surgical part of therapy for each half of the patient groups included surface decontamination with diode laser light ( 1‐watt output , maximum of 20 seconds ) in addition to conventional procedures . The values of the laser‐supported therapy were lower than those specified in the relevant literature . The relapse rate of the two diseases ( 13 % for the periimplantitis and 23 % for the parodontopathy group ) after 5 years was lower than the comparative values of research ed literature where decontamination was not included in the therapy . We think that integrating diode laser light decontamination in the approved treatment schemes for periimplantitis and parodontitis contributes considerably to the success of this therapy . ( Implant Dent 2000;9:247‐251 OBJECTIVES The study aim ed at investigating the impact of two surface debridement/decontamination ( DD ) methods on the clinical outcomes of combined surgical treatment of peri-implantitis . MATERIAL AND METHODS Thirty-two patients suffering from advanced peri-implantitis ( n=38 combined supra- and intra-bony defects ) were treated with flap surgery , granulation tissue removal , and implantoplasty at buccally and supracrestally exposed implant parts . The intra-bony aspects were r and omly allocated to surface DD using either ( i ) an Er : YAG laser ( ERL ) device , or ( ii ) plastic curets+cotton pellets+sterile saline ( CPS ) . In both groups , the intra-bony component was augmented with a natural bone mineral and covered with a collagen membrane . Clinical and radiographic parameters were recorded at baseline and after 6 months of non-submerged healing . RESULTS Two patients were lost during follow-up . At 6 months , ERL-treated sites failed to reveal higher reductions in mean bleeding on probing ( ERL : 47.8 ± 35.5 versus CPS : 55.0 ± 31.1 % ) and CAL values ( ERL : 1.5 ± 1.4 versus CPS : 2.2 ± 1.4 mm ) when compared with the CPS group . Both groups exhibited a comparable radiographic bone fill at the intra-bony defect component . CONCLUSION The study failed to demonstrate a significant impact of the method of surface DD on the clinical outcome following combined surgical therapy of advanced peri-implantitis lesions AIM To compare the effectiveness of treatment of peri-implantitis with a novel ultrasonic device , the Vector system , with that of subgingival debridement with carbon fiber curettes . MATERIAL AND METHODS The study , comprising 11 patients with at least two screw type implants with bleeding on probing ( BOP ) , probing pocket depth ( PPD ) > or = 5 mm , and at least 1.5 mm radiographic bone loss and exposed implant threads , was carried out as a single blind r and omized clinical trial . At baseline one r and omly chosen implant in each patient was treated by the Vector system ( test ) while the other implant ( control ) was treated by submucosal debridement with a carbon fiber curette . After 3 months , the same treatments were repeated . Plaque , BOP , and PPD were recorded on all implant surfaces at baseline , and after 3 and 6 months . Bone levels were recorded on radiographs taken prior to the start of the study , and after 6 months . RESULTS Oral hygiene around both test and control implants was improved at 3 and 6 months compared with baseline . At 6 months , four of the Vector-treated sites , and only one site treated with curettes , had stopped to bleed . In neither the test nor the control group , were there any differences between baseline and 6 months regarding PPD and bone levels . CONCLUSION Although there was a greater reduction in the number of sites with BOP following treatment with the Vector system than following instrumentation with carbon fiber curettes , there was no significant difference between the two methods This clinical study reports on the results of a new method in the treatment of peri-implantitis . The surfaces of 24 plasma flame-sprayed cylindric implants in 17 patients who were diagnosed with peri-implantitis were decontaminated with a combination of toluidine blue ( 100 micrograms/mL ) and laser irradiation at a wavelength of 906 nm . Bone defects were filled with autogenous bone using e-PTFE membranes for retention of the grafting material . Premature membrane exposure occurred in all patients after an average of 3 weeks ( + /- 10 days ) , which required immediate removal of the exposed membrane in 1 patient . Since the soft tissue showed minimal signs of inflammation , the membranes were left in situ for another 6 weeks in all other patients . The mean radiographic peri-implant bone gain was 2 mm + /- 1.90 mm after 9.5 months ( maxilla 2.5 mm + /- 2.38 mm ; m and ible 1.9 mm + /- 1.87 mm ) . Two implants around which the initial bone defect had already reached the basket had to be removed after 10 months and 35 months , respectively , despite radiographic evidence of improvement of the peri-implant defect . The longer the membrane stayed in situ , the more bone was gained , as long as the membrane was covered by soft tissue ( P = .01 ) . However , the longer an exposed membrane was left in place , the smaller the result ant bone gain ( P = .0001 ) . Therefore , despite the absence of clinical signs of inflammation , exposed membranes should be removed immediately . The short-term results of this study corroborate the efficacy of the applied treatment method in prolonging the service time of dental implants involved with peri-implantitis OBJECTIVES The aim of this prospect i ve cohort study was to compare two regenerative surgical treatment modalities for peri-implantitis . MATERIAL AND METHODS Thirty-six patients having a minimum of one osseointegrated implant , with a progressive loss of bone amounting to > or =3 threads ( 1.8 mm ) following the first year of healing , combined with bleeding and /or pus on probing , were involved in this study . The patients were assigned to two different treatment strategies . After surgical exposure of the defect , granulomatous tissue was removed and the infected implant surface was treated using 3 % hydrogen peroxide . The bone defects were filled with a bone substitute ( Algipore ) . In 17 patients ( Group 1 ) , a resorbable membrane ( Osseoquest ) was placed over the grafted defect before suturing . In 19 patients ( Group 2 ) , the graft was used alone . RESULTS One-year follow-up demonstrated clinical and radiographic improvements . Probing depths were reduced by 2.9 mm in Group 1 and by 3.4 mm in Group 2 . Defect fill amounted to 1.5 and 1.4 mm , respectively . There was no significant difference between the groups . CONCLUSION It is possible to treat peri-implant defects with a bone substitute , with or without a resorbable membrane OBJECTIVES The aim of this prospect i ve , parallel group design ed , r and omized controlled clinical study was to evaluate the effectiveness of an air-abrasive device ( AAD ) for non-surgical treatment of peri-implantitis . MATERIAL AND METHODS Thirty patients , each of whom displayed at least one implant with initial to moderate peri-implantitis , were enrolled in an oral hygiene program ( OHI ) and r and omly instrumented using either ( 1 ) AAD ( amino acid glycine powder ) or ( 2 ) mechanical debridement using carbon curets and antiseptic therapy with chlorhexidine digluconate ( MDA ) . Clinical parameters were measured at baseline , 3 and 6 months after treatment [ e.g. bleeding on probing ( BOP ) , probing depth ( PD ) , clinical attachment level ( CAL ) ] . RESULTS At 6 months , AAD group revealed significantly higher ( p<0.05 ; unpaired t-test ) changes in mean BOP scores when compared with MDA-treated sites ( 43.5 ± 27.7%versus 11.0 ± 15.7 % ) . Both groups exhibited comparable PD reductions ( AAD : 0.6 ± 0.6 mm versus MDA : 0.5 ± 0.6 mm ) and CAL gains ( AAD : 0.4 ± 0.7 mm versus MDA Output:	AUTHORS ' CONCLUSIONS There is no reliable evidence suggesting which could be the most effective interventions for treating peri-implantitis . This is not to say that currently used interventions are not effective . Follow-up longer than 1 year suggested recurrence of peri-implantitis in up to 100 % of the treated cases for some of the tested interventions . As this can be a chronic disease , re-treatment may be necessary .
MS21202	*TASK* the task is to summarize an input biomedical literature in six sentences *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 : Little is known about missed rates of upper gastrointestinal cancer ( UGC ) in Western population s , with most data originating from Japanese centers quoting high missed rates of 23.5–25.8 % . The objective of this study was to better define missed rates of esophagogastroduodenoscopy ( EGD ) and the natural history of UGC in a Western population that underwent an initial EGD without cancer , but were subsequently diagnosed with a UGC . Our hypothesis was that a normal EGD rarely misses the detection of UGC . METHODS : This is a retrospective cohort study . A prospect ively maintained electronic data base was used to identify all patients who underwent EGD between 1990 and 2004 at the study institution . Patients in this cohort who were diagnosed with UGC before 2006 were identified through the Western Australian Cancer Registry . We defined missed cancers as those diagnosed within 1 year of EGD , possible missed cancers as those diagnosed 1–3 years after EGD , and new cancers as those diagnosed more than 3 years after EGD . This study had no interventions and was conducted at a tertiary referral center . The main outcome measurement included UGC . RESULTS : Of the 28,064 EGDs performed , UGC was diagnosed subsequent to the procedure in 116 cases ( 0.41 % ) . There were 29 missed cancers , 26 possible missed cancers , and 75 new cancers . Of the missed cancers , 11 were esophageal , 15 were gastric , and 3 were duodenal . In 69 % ( n=20 ) of the missed cancers , an abnormality was described at the site of malignancy . In 59 % ( n=17 ) of the missed cancers , the indication for EGD was an alarm symptom of dysphagia or suspected blood loss . In an univariate analysis , the presence of an alarm symptom was related to missed cancers , whereas operator experience , trainee participation , and usage of newer equipment were not . One of the main limitations of this study is that it was a retrospective review . CONCLUSIONS : UGC is rare after normal EGD , confirming the high accuracy of EGD . Institutional approval was granted for the conduct of this study A system has been constructed to evaluate the design , implementation , and analysis of r and omized control trials ( RCT ) . The degree of quadruple blinding ( the r and omization process , the physicians and patients as to therapy , and the physicians as to ongoing results ) is considered to be the most important aspect of any trial . The analytic techniques are scored with the same emphasis as is placed on the control of bias in the planning and implementation of the studies . Description of the patient and treatment material s and the measurement of various controls of quality have less weight . An index of quality of a RCT is proposed with its pros and cons . If published papers were to approximate these principles , there would be a marked improvement in the quality of r and omized control trials . Finally , a reasonable st and ard design and conduct of trials will facilitate the interpretation of those with conflicting results and help in making valid combinations of undersized trials BACKGROUND AND AIM Upper GI endoscopy ( UGE ) is essential for the diagnosis of gastrointestinal diseases . Mucus and bubbles may decrease mucosal visibility . The use of mucolytics could improve visualization . Our aim was to determine whether premedication with simethicone or simethicone plus N-acetylcysteine is effective in improving visibility during UGE . METHODS This was a r and omized , double-blinded , placebo-controlled trial with 2 control groups : no intervention and water 100 mL ( W ) ; and 3 intervention groups : simethicone 200 mg ( S ) ; S + N-acetylcysteine ( NAC ) 500 mg ( S+NAC500 ) ; and S + NAC 1000 mg ( S+NAC1000 ) . The solution was ingested 20 minutes before UGE . Gastric visibility was evaluated in 4 segments with a previously described scale . A score of less than 7 points was defined as adequate visibility ( AV ) . Water volume was used to improve visibility , and adverse reactions were evaluated as a secondary outcome . Multiple group comparison was performed using non-parametric one-way analysis of variance ( ANOVA ) . RESULTS Two hundred thirty patients were included in the study , 68 % female , mean age 49 years . The most common indication for UGE was epigastric pain/dyspepsia ( 33 % ) . AV was more frequent in the S+NAC500 and S+NAC1000 groups ( 65 % and 67 % ) compared with no intervention ( 44 % , P = .044 ) and water ( 41 % , P = .022 ) . The gastric total visibility scale ( TVS ) was significantly better in the S+NAC500 and S+NAC1000 groups compared with water ( P = .03 and P = .008 ) . Simethicone was not different from no intervention and water . S+NAC1000 required less water volume to improve visibility . No adverse reactions from the study drugs were observed . CONCLUSIONS Premedication with S+NAC500 and S+NAC1000 improves visibility during UGE . The use of simethicone did not show improvements in gastric visibility . TVS was worse in patients using water alone . ( Clinical trial registration number : NCT 01653171 . ) Background and study aim Upper endoscopy is the most common method for the diagnosis of upper gastrointestinal tract diseases . The aim of this study was to determine whether premedication with simethicone or N-acetylcysteine improves mucosal visualization during upper endoscopy . Patients and methods This was a r and omized , double-blind , placebo-controlled study of 297 patients scheduled for upper endoscopy who were premedicated 15 - 30 minutes before the procedure with : 100 mL of water ( placebo , group A ) ; water plus 100 mg simethicone ( group B ) ; water plus 100 mg simethicone plus 600 mg N-acetylcysteine ( group C ) . The primary outcome measure was the quality of mucosal visualization ( score : excellent , adequate or inadequate ) . Results The addition of simethicone ( group B ) or simethicone plus N-acetylcysteine to the water ( group C ) improved the visualization scores of endoscopies compared with water alone ( group A ) . In particular , groups B and C produced a significantly higher percentage of endoscopies with excellent visualization for the esophagus ( 91.1 % and 86.7 % , respectively , vs. 71.4 % in group A ; P < 0.001 ) and stomach ( 76.2 % and 74.5 % vs. 38.8 % in group A ; P < 0.001 ) . For the duodenum , the use of simethicone also showed an increase in the endoscopies with excellent visualization compared with water alone ( 85.1 % vs. 73.5 % ; P = 0.042 ) . There were no significant differences in scores between groups B and C or between gastric scores in patients with previous subtotal gastrectomy ( B and C vs. A ) : 60.0 % and 42.1 % vs. 28.6 % ( P = 0.14 ) . The rate of reported lesions was higher in group B but without statistical significance . Conclusions Premedication with simethicone result ed in better mucosal visibility . Such premedication might improve diagnostic yield , and should be considered for st and ard practice . Trial registered at Clinical Trials.gov ( NCT02357303 ) BACKGROUND Simethicone improves endoscopic visibility and diagnostic accuracy during colonoscopy and capsule endoscopy . Nevertheless , there have been limited data on its usefulness in esophagogastroduodenoscopy ( EGD ) . OBJECTIVE To evaluate the effectiveness of simethicone on enhancing endoscopic visibility in patients undergoing EGD . MATERIAL AND METHOD 121 patients were r and omized to take 2 ml ofeither liquid simethicone or placebo in 60 ml of water at 15 - 30 minutes before EGD . The severity scores of foam and bubbles at the esophagus , stomach and duodenum were compared . RESULTS Simethicone improved endoscopic visibility by diminishing mean cumulative ( 6.83 + /- 2.4 vs. 11.05 + /- 2.6 , p < 0.001 ) and local scores offoam and bubbles at all areas , and decreased the number and timing ofadjunctive simethicone washing ( 17.5 % vs. 74.1 % , p < 0.001 and 0 vs. 19 seconds , p < 0.001 ) . Simethicone increased endoscopist and patient satisfaction significantly without having adverse effects . CONCLUSION Using simethicone before EGD enhances endoscopic visibility , reduces adjunctive simethicone washing and increases endoscopist and patient satisfaction AIM To evaluate the efficacy of 5 mL simethicone solution in decreasing gastric foam if given at least 30 min before gastroscopy . METHODS This was a r and omized , placebo controlled , endoscopist blinded study performed at Changi General Hospital . Patients were at least 21 years old , had no prior surgical resection of the upper gastrointestinal tract , and scheduled for elective diagnostic gastroscopies . The primary outcome was the total mucosal visibility score ( TMVS ) which was evaluated using McNally score . The sample size was calculated to be 24 per group ( SD 2.4 , 80 % power , P < 0.05 , 2- sample t test ) . RESULTS Fifty-four patients were r and omised to receive either simethicone [ 1 mL liquid simethicone ( 100 mg ) in 5 mL of water ] or placebo ( 5 mL of water ) at least 30 min before their gastroscopy . Six accredited consultants conducted the gastroscopy , and the interobserver agreement of scoring TMVS was good with a Kappa statistic of 0.73 . The simethicone group had significantly better mean TMVS compared to placebo ( 5.78 ± SD 1.65 vs 8.89 ± SD 1.97 , P < 0.001 ) . The improvement was statistically significant for the duodenum and the gastric antrum , angularis , body , and fundus . Percent 51.9 of patients in the simethicone group had a TMVS of 4 ( no bubbles at all ) to 5 ( only 1 area with minimal bubbles ) , while in the placebo group 3.7 % of patients had TMVS of 4 or 5 . The number needed to treat was 2.1 to avoid a TMVS of 6 and more . The simethicone group also had a significantly shorter procedure time with less volume of additional flushes required during gastroscopy to clear away obscuring gastric foam . CONCLUSION With a premedication time of at least 30 min , 5 mL simethicone can significantly decrease gastric foam , decrease the volume of additional flushes , and shorten gastroscopy time OBJECTIVES To investigate whether a 360-degree horizontal turn after oral premedication with simethicone improves the mucosal visibility during gastroendoscopic examination , and to determine the proper time to turn over the patient . METHODS This study involved 993 patients scheduled for gastroendoscopy . Just before gastroendoscopy , after oral premedication with simethicone , patients were r and omly assigned to three groups : in Group A , patients waited for 20 min before gastroendoscopy ; in Group B , patients were separately waited for 5/10/15/20 min and were then turned 360 degrees just before gastroendoscopy ; in Group C , patients were immediately turned 360 degrees and then separately waited for 5/10/15/20 min before examination . The sum of the gastric mucosal visibility scores ( MVS ) was calculated after the examination . The MVS and proportion of images with higher visibility scores for the mucosal surface . Lower scores indicate better visibility of the mucosal surface . RESULTS In Groups B and Groups C , when waiting time more than 10 min had lower mean total MVS than Group A. The MVS of four subgroups of Group B were not different from those of Group C. CONCLUSION Oral premedication with simethicone and immediately make a body posture change ( turning over 360 degrees ) then waiting for 10min can increase the image quality during gastroendoscopy and effectively decrease the premedication time AIM : To evaluate the effects of the various methods of small bowel preparation on the quality of visualization of the small bowel and the gastrointestinal transit time of capsule endoscopy ( CE ) . METHODS : Ninety patients referred for CE were prospect ively r and omized to three equal groups according to the preparation used : ( a ) a control group , in which patients were requested to drink 1 L of clear liquids only , 12 h before the examination ; ( b ) a purgative group , in which patients were requested to ingest 1 L of a polyethylene glycol (PEG)/electrolyte solution only , 12 h before the examination ; or ( c ) a purgative combined with simethicone group ( P-S group ) , in which patients were requested to ingest 1 L of PEG , 12 h before the examination , and 300 mg of simethicone , 20 min before the examination . Effects of the different bowel preparations on the gastric transit time ( GTT ) , small bowel trans Output:	Conclusions The findings of current study on 1,099 patients successfully demonstrate that the pre-procedure oral administration of Simethicone ± N-acetylcysteine improves mucosal visualization and mucosal visualization score during OGD
MS21203	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The effects of long-term functional electrical stimulation (FES)-assisted walking on ankle dynamic stiffness were examined in spinal cord-injured ( SCI ) subjects with incomplete motor function loss . A parallel-cascade system identification method was used to identify intrinsic and reflex contributions to dynamic ankle stiffness at different ankle positions while subjects remained relaxed . Intrinsic stiffness dynamics were well modeled by a linear second-order model relating intrinsic torque to joint position . Reflex stiffness dynamics were accurately described by a linear third-order model relating halfwave rectified velocity to reflex torque . We examined four SCI subjects before and after long-term FES-assisted walking ( > 16 mo ) . Another SCI subject , who used FES for only five months was examined 12 mo latter to serve as a non-FES , SCI control . Reflex stiffness decreased in FES subjects by an average of 53 % following FES-assisted walking , intrinsic stiffness also dropped by 45 % . In contrast , both reflex and intrinsic stiffness increased in the non-FES , SCI control . These findings suggest that FES-assisted walking may have therapeutic effects , helping to reduce abnormal joint stiffness Among the objectives of spinal cord injury ( SCI ) rehabilitation , ( i ) prevention of bony , muscular and joint trophism and ( ii ) limitation of spastic hypertone represent important goals to be achieved . The aim of this study is to use functional electrical stimulation ( FES ) to activate pedaling on cycle-ergometer and analyse effects of this technique for a rehabilitation training in SCI persons . Five spinal cord injured subjects were recruited and underwent a two months FES-cycling training . Our results show an increase of thigh muscular area and endurance after the FES-cycling training , without any increase of spasticity . This approach , which is being vali date d on a larger pool of patients , represents a potential tool for improving the rehabilitation outcome of complete and incomplete SCI persons The goal of this research was to determine if cutaneous electrotherapy would temporarily reduce muscle spasticity . Five traumatically brain injured ( TBI ) and five spinal cord injured ( SCI ) subjects , all with clinical ly evident spasticity , received surface electrical stimulation over the tibialis anterior muscle . Using the Spasticity Measurement System , stiffness around the ankle was measured before , immediately after , and 24 hours after treatment . With stimulation , ipsilateral ankle viscoelastic stiffness immediately decreased in 9 of 10 subjects and remained significantly depressed for up to 24 hours . Contralateral ankle spasticity did not significantly change . Using the same subjects under sham conditions , no significant decrements in spasticity occurred . In a subjective survey , only SCI participants reported functionally evident spasticity reductions . Also within this subgroup , efficacy of treatment was directly proportional to the severity of pre-stimulation clonus . We conclude that ( 1 ) cutaneous electrotherapy transiently decreases both TBI and SCI related spasticity and ( 2 ) pre-stimulation clonus may function as a clinical indicator of SCI patients most likely to benefit from this process This study examined the effects of altering surface neuromuscular electrical stimulation ( SNMES ) parameters on the specific tension of the quadriceps femoris muscle . Seven able-bodied subjects had magnetic resonance images taken of both thighs prior to and immediately after four SNMES protocol s to determine the activated muscle cross-sectional area ( CSA ) . The four protocol s were : ( 1 ) research ( RES , 100 Hz , 450 μs , and amplitude set to evoke 75 % of maximal voluntary isometric torque , MVIT ) ; ( 2 ) pulse duration ( PD , 100 Hz , 150 μs , same current as in RES ) ; ( 3 ) frequency ( FREQ , 25 Hz , 450 μs , and same current as in RES ) ; ( 4 ) amplitude ( AMP , 100 Hz , 450 μs , and current set to evoke the average of the initial torques of PD and FREQ , 45 ± 9 % of MVIT ) . Reducing the amplitude of the current from 75 to 45 % of MVIT did not alter specific tension , 25 ± 8 N/cm2 , suggesting that the amplitude probably affects torque and the area of activated muscle proportionally . Shortening the pulse duration from 450 to 150 μs caused specific tension to drop from 25 ± 6 to 20 ± 6 N/cm2 ( P < 0.05 ) , indicating that pulse duration increased torque and the activated CSA disproportionally . Alternatively , reducing the frequency from 100 to 25 Hz decreased specific tension from 25 ± 6 to 17 ± 4 N/cm2 ( P < 0.05 ) , suggesting that the frequency increased torque without affecting the activated CSA . Clinicians who administer SNMES should be aware of the magnitude of adaptations to a given amplitude , pulse duration , and frequency The objective of this prospect i ve cohort study was to investigate alterations in body composition variables and spasticity following subtetanic neuromuscular electrical stimulation ( NMES ) training in an adult population with spinal cord injury ( SCI ) . Fourteen sedentary adults with SCI ( thoracic [T]4-T11 ; American Spinal Injury Association Impairment Scale A/B ; time since injury : 10.17 + /- 11.17 yr ) were recruited from the National SCI data base . Four adhesive electrodes ( 175 cm2 each ) were placed bilaterally on the proximal and distal quadriceps and hamstrings muscle groups and subtetanic contractions were elicited using a h and held NMES device . Lean body mass ( LBM ) and other body composition variables were measured using dual-energy X-ray absorptiometry . Spasticity was measured using the Spinal Cord Assessment Tool for Spastic Reflexes ( SCATs ) and visual analog scales . Verbal and written feedback was obtained to subjectively evaluate spasticity . LBM and spasticity measurements were taken before and after an 8 wk NMES training program in order to assess change . A statistically significant increase in lower-limb LBM , i.e. , muscle tissue ( p > 0.001 ) , and a reduction in SCATs ( p < 0.001 ) score , indicating reduced spasticity , was observed . Subjective responses were positive . Improvements in body composition and SCATs scores indicate that subtetanic NMES training elicits favorable responses and may have important clinical implication s for an SCI population OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity QUESTION Does functional electrical stimulation ( FES ) cycling increase urine output and decrease lower limb swelling and spasticity in people with recent spinal cord injury ? DESIGN R and omised cross-over trial . PARTICIPANTS Fourteen participants with a recent motor complete spinal cord injury were consecutively recruited from two spinal cord injury units in Sydney . INTERVENTION Participants were r and omised to an experimental phase followed by a control phase or vice versa , with a 1-week washout period in between . The experimental phase involved FES cycling four times a week for two weeks and the control phase involved st and ard rehabilitation for two weeks . Assessment s by a blinded assessor occurred at the beginning and end of each phase . Allocation was concealed and an intention-to-treat analysis was performed . OUTCOME MEASURES The primary outcome was urine output ( mL/hr ) and the secondary outcomes were lower limb circumference , and spasticity using the Ashworth Scale , and the Patient Reported Impact of Spasticity Measure ( PRISM ) . In addition , participants were asked open-ended questions to explore their perceptions about treatment effectiveness . RESULTS All participants completed the study . The mean between-group difference ( 95 % CI ) for urine output was 82mL/hr ( -35 to 199 ) . The mean between-group differences ( 95 % CI ) for lower limb swelling , spasticity ( Ashworth ) , and PRISM were -0.1 cm ( -1.5 to 1.2 ) , -1.9 points ( -4.9 to 1.2 ) and -5 points ( -13 to 2 ) , respectively . All point estimates of treatment effects favoured FES cycling . Participants reported many benefits from FES cycling . CONCLUSION There were no clear effects of FES cycling on urine output , swelling and spasticity even though all point estimates of treatment effects favoured FES cycling and participants perceived therapeutic effects . TRIAL REGISTRATION ACTRN12611000923965 Objective : Spasticity following spinal cord injury ( SCI ) can impair function and affect quality of life . This study compared the effects of transcutaneous electrical nerve stimulation ( TENS ) and functional electrical stimulation ( FES ) on lower limb spasticity in patients with SCI . Design : Double blind r and omized crossover design . Setting : Neuro-rehabilitation unit , Manipal University , India . Participants : Ten participants ( age : 39 ± 13.6 years , C1–T11 , 1–26 months post SCI ) with lower limb spasticity were enrolled in this study . Interventions : Participants were administered electrical stimulation with TENS and FES ( duration - 30 minutes ) in a cross over manner separated by 24 hours . Outcome Measures : Spasticity was measured using modified Ashworth scale ( MAS ) [ for hip abductors , knee extensors and ankle plantar flexors ] and spinal cord assessment tool for spastic reflexes ( SCATS ) . Assessment s were performed at baseline , immediately , 1 hour , 4 hours , and 24 hours post intervention . Results : A between group analysis did not show statistically significant differences between FES and TENS ( P > 0.05 ) . In the within group analyses , TENS and FES significantly reduced spasticity up to 4 hours in hip adductors and knee extensors ( P < 0.01 ) . SCATS values showed significant reductions at 1 hour ( P = 0.01 ) following TENS and 4 hours following FES ( P = 0.01 ) . Conclusion : A single session of electrical stimulation with FES and TENS appears to have similar anti-spasticity effects that last for 4 hours . The findings of this preliminary study suggest that both TENS and FES have the potential to be used as therapeutic adjuncts to relieve spasticity in the clinic . In addition , FES may have better effects on patients presenting with spastic reflexes STUDY DESIGN Experimental laboratory study . OBJECTIVES The primary purpose was to investigate the independent effects of current amplitude , pulse duration , and current frequency on muscle fatigue during neuromuscular electrical stimulation ( NMES ) . A second purpose was to determine if the ratio of the evoked torque to the activated area could explain muscle fatigue . BACKGROUND Parameters of NMES have been shown to differently affect the evoked torque and the activated area . The efficacy of NMES is limited by the rapid onset of muscle fatigue . METHODS AND MEASURES Seven healthy participants underwent 4 NMES protocol s that were r and omly applied to the knee extensor muscle group . The NMES protocol s were as follows : st and ard protocol ( Std ) , defined as 100-Hz , 450-micros pulses and amplitude set to evoke 75 % of maximal voluntary isometric torque ( MVIT ) ; short pulse duration protocol ( SP ) , defined as 100-Hz , 150-micros pulses and amplitude set to evoke 75 % of MVIT ; low-frequency protocol ( LF ) Output:	The identified stimulation parameters were frequency of 20–30 Hz , pulse duration of 300–350 & mgr;s , and amplitude of the current greater than 100 mA. Neuromuscular electrical stimulation/functional electrical stimulation provides an effective rehabilitation strategy in managing spasticity .
MS21204	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background To investigate the risk of first-time acute coronary syndrome ( ACS ) , stroke and venous thromboembolism ( VTE ) in patients with ankylosing spondylitis ( AS ) , psoriatic arthritis ( PsA ) and undifferentiated spondyloarthritis ( uSpA ) , compared to each other and to the general population ( GP ) . Methods This is a prospect i ve nationwide cohort study . Cohorts with AS ( n = 6448 ) , PsA ( n = 16,063 ) and uSpA ( n = 5190 ) patients and a GP ( n = 266,435 ) cohort , were identified 2001–2009 in the Swedish National Patient and Population registers . The follow-up began 1 January 2006 , or 6 months after the first registered spondyloarthritis ( SpA ) diagnosis thereafter , and ended at ACS/stroke/VTE event , death , emigration or 31 December 2012 . Crude and age- and sex-st and ardized incidence rates ( SIRs ) and hazard ratios ( HRs ) were calculated for incident ACS , stroke or VTE , respectively . Results St and ardized to the GP cohort , SIRs for ACS were 4.3 , 5.4 and 4.7 events per 1000 person-years at risk in the AS , PsA and uSpA cohort , respectively , compared to 3.2 in the GP cohort . SIRs for stroke were 5.4 , 5.9 and 5.7 events per 1000 person-years at risk in the AS , PsA and uSpA cohort compared to 4.7 in the GP cohort . Corresponding SIRs for VTE were 3.6 , 3.2 and 3.5 events per 1000 person-years at risk compared to 2.2 in the GP cohort . Age- and sex-adjusted HRs ( 95 % CI ) for ACS events were significantly increased in AS ( 1.54 ( 1.31–1.82 ) ) , PsA ( 1.76 ( 1.59–1.95 ) ) and uSpA ( 1.36 ( 1.05–1.76 ) ) compared to GP . Age-adjusted HRs for ACS was significantly decreased in female AS patients ( 0.59 ( 0.37–0.97 ) ) compared to female PsA patients . Age- and sex-adjusted HRs for stroke events were significantly increased in AS ( 1.25 ( 1.06–1.48 ) ) and PsA ( 1.34 ( 1.22–1.48 ) ) , and nonsignificantly increased in uSpA ( 1.16 ( 0.91–1.47 ) ) compared to GP . For VTE the age- and sex-adjusted HRs for AS , PsA and uSpA were equally and significantly increased with about 50 % compared to GP . Conclusions Patients with AS , PsA and uSpA are at increased risk for ACS and stroke events , which emphasizes the importance of identification of and intervention against cardiovascular risk factors in SpA patients . Increased alertness for VTE is warranted in patients with STUDY OBJECTIVES To underst and reasons for compliance and non-compliance with a home based exercise regimen by patients with osteoarthritis of the knee . DESIGN A qualitative study , nested within a r and omised controlled trial , examining the effectiveness of physiotherapy in reducing pain and increasing mobility in knee osteoarthritis . In the intervention arm , participants undertook a series of simple exercises and repositioning of the kneecap using tape . In depth interviews were conducted with a subset of participants in the intervention arm using open ended questions , guided by a topic schedule , to encourage patients to describe their experiences and reflect on why they did or did not comply with the physiotherapy . Interviews were audiotaped , fully transcribed and analysed thematically according to the method of constant comparison . A model explaining factors influencing compliance was developed . SETTING Patients were interviewed at home . The study was nested within a pragmatic r and omised controlled trial . PARTICIPANTS Twenty participants in the intervention arm of the r and omised trial were interviewed three months after they had completed the physiotherapy programme . Eight were interviewed again one year later . MAIN RESULTS Initial compliance was high because of loyalty to the physiotherapist . Reasoning underpinning continued compliance was more complex , involving willingness and ability to accommo date exercises within everyday life , the perceived severity of symptoms , attitudes towards arthritis and comorbidity and previous experiences of osteoarthritis . A necessary precondition for continued compliance was the perception that the physiotherapy was effective in ameliorating unpleasant symptoms . CONCLUSIONS Non-compliance with physiotherapy , as with drug therapies , is common . From the patient 's perspective , decisions about whether or not to comply are rational but often can not be predicted by therapists or research ers . Ultimately , this study suggests that health professionals need to underst and reasons for non-compliance if they are to provide supportive care and trialists should include qualitative research within trials whenever levels of compliance may have an impact on the effectiveness of the intervention Fernández-de-las-Peñas C , Alonso-Blanco C , Alguacil-Diego IM , Miangolarra-Page JC : One-year follow-up of two exercise interventions for the management of patients with ankylosing spondylitis : A r and omized controlled trial . Am J Phys Med Rehabil 2006;85:559–567 . Objective : To assess the long-term effects on functional and mobility outcomes of two exercise interventions for the management of patients with ankylosing spondylitis . Design : In an extended 12-mo follow-up of a r and omized controlled trial , 40 patients who were diagnosed with ankylosing spondylitis according to the modified criteria of New York , allocated to control or experimental groups using a r and om numbers table , and who performed their respective exercise program at least three times per month , were included in this long-term study . The control group was treated during 15 sessions with a conventional exercise regimen in ankylosing spondylitis , whereas the experimental group received 15 sessions of exercises based on the treatment of the shortened muscle chains following the guidelines described by the Global Posture Reeducation method . These patients were followed up and assessed again 1 yr after entering the study , reapplying the same vali date d indexes : BASMI ( Bath Ankylosing Spondylitis Metrology Index [ tragus to wall distance , modified Schober test , cervical rotation , lumbar side flexion , and intermalleolar distance ] ) , BASDAI ( Bath Ankylosing Spondylitis Disease Activity Index ) , and BASFI ( Bath Ankylosing Spondylitis Functional Index ) . Results : The intragroup comparison between follow-up and postintervention data showed that both groups decrease their clinical and functional measures during the follow-up period . This decrease was only significant for lumbar side flexion and intermalleolar distance measurements , being more significant in the control group ( P = 0.001 and P = 0.002 , respectively ) . Intragroup differences between follow-up and preintervention assessment s revealed that improvements in all mobility measures of the BASMI index and in the BASFI index were partially maintained at the 12-mo follow-up in the experimental group but not in the control group . The intergroup comparison ( unpaired t test analysis ) between changes on each outcome during the long-term follow-up ( post – follow-up ; and pre – follow-up ) showed no significant differences in the decrease between postintervention and follow-up data between the study groups . On the other h and , the intergroup comparison between preintervention and follow-up data revealed significant differences in almost all mobility measures of the BASMI index ( except for cervical rotation ) and in the BASFI index , in favor of the experimental group . Conclusions : An exercise regimen based on the Global Posture Reeducation method and focusing on specific strengthening and flexibility exercises of the shortened muscle chains offers promising short- and long-term results in the management of patients who have ankylosing spondylitis Background Evidence suggests people with axial spondyloarthritis ( axial SpA ) should exercise up to five times per week but lack of time , symptoms , cost and distance are barriers to regular exercise in axial SpA. Personalised exercise programmes delivered via the internet might support people with axial SpA to reach these exercise targets . The aim of this study is to investigate the effect of , and adherence to , a 12 month personalised web-based physiotherapy programme for people with axial SpA. Methods Fifty people with axial SpA will be recruited to this prospect i ve , interventional cohort study . Each participant will be assessed by a physiotherapist and an individualised exercise programme set up on www.webbasedphysio.com . Participants will be asked to complete their programme five times per week for 12 months . With the exception of adherence , data will be collected at baseline , 6 and 12 months . Discussion The primary outcome measure is adherence to the exercise programme over each four week cycle ( 20 sessions maximum per cycle ) and over the 12 months . Secondary measures include function ( BASFI ) , disease activity ( BASDAI ) , work impairment ( WPAI : SpA ) , quality of life ( ASQoL , EQ5D ) , attitude to exercise ( EMI-2 , EAQ ) , spinal mobility ( BASMI ) , physical activity and the six minute walk test . Participants will also be interviewed to explore their adherence , or otherwise , to the intervention . This study will determine the adherence and key clinical outcomes of a targeted web-based physiotherapy programme for axial SpA. This data will inform clinical practice and the development and implementation of similar programmes . Trial registration Clinical Trials.gov : NCT02666313 , 20th January Paper diaries are commonly used in health care and clinical research to assess patient experiences . There is concern that patients do not comply with diary protocol s , possibly invalidating the benefit of diary data . Compliance with paper diaries was examined with a paper diary and with an electronic diary that incorporated compliance-enhancing features . Participants were chronic pain patients and they were assigned to use either a paper diary instrumented to track diary use or an electronic diary that time-stamped entries . Participants were instructed to make three pain entries per day at predetermined times for 21 consecutive days . Primary outcome measures were reported vs actual compliance with paper diaries and actual compliance with paper diaries ( defined by comparing the written times and the electronically-recorded times of diary use ) . Actual compliance was recorded by the electronic diary . Participants su bmi tted diary cards corresponding to 90 % of assigned times ( + /-15 min ) . However , electronic records indicated that actual compliance was only 11 % , indicating a high level of faked compliance . On 32 % of all study days the paper diary binder was not opened , yet reported compliance for these days exceeded 90 % . For the electronic diary , the actual compliance rate was 94 % . In summary , participants with chronic pain enrolled in a study for research were not compliant with paper diaries but were compliant with an electronic diary with enhanced compliance features . The findings call into question the use of paper diaries and suggest that electronic diaries with compliance-enhancing features are a more effective way of collecting diary information OBJECTIVES To identify factors that are associated with older patients ' engagement in exercise in the 6 months after hospital discharge . DESIGN A prospect i ve observational study using qualitative and quantitative evaluation . SETTING Follow-up of hospital patients in their home setting after discharge from a metropolitan general hospital . PARTICIPANTS Participants ( N=343 ) were older patients ( mean age ± SD , 79.4 ± 8.5y ) discharged from medical , surgical , and rehabilitation wards and followed up for 6 months after discharge . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Self-perceived awareness and risk of falls measured at discharge with a survey that addressed elements of the Health Belief Model . Engagement and self-reported barriers to engagement in exercise measured at 6 months after discharge using a telephone survey . RESULTS Six months after discharge , 305 participants remained in the study , of whom 109 ( 35.7 % ) were engaging in a structured exercise program . Multivariable logistic regression analysis demonstrated participants were more likely to be engaging in exercise if they perceived they were at risk of serious injury from a fall ( odds ratio [ OR ] = .61 ; 95 % confidence interval [ CI ] , .48-.78 ; P<.001 ) , if exercise was recommended by the hospital physiotherapist ( OR=1.93 ; 95 % CI , 1.03 - 3.59 ; P=.04 ) , and if they lived with a partner ( OR=1.97 ; 95 % CI , 1.18 - 3.28 ; P=.009 ) . Barriers to exercise identified by 168 participants ( 55 % ) included low self-efficacy , low motivation , medical problems such as pain , and impediments to program delivery . CONCLUSIONS Older patients have low levels of engagement in exercise after hospital discharge . Research ers should design exercise programs that address identified barriers and facilitators , and provide education to enhance motivation and self-efficacy to exercise in this population OBJECTIVE To determine the extent to which measures of foot and ankle strength , range of motion , posture , and deformity are associated with performance in a battery of balance and functional ability tests in older adults . DESIGN Cross-sectional study of people over 65 years . SETTING Community . PARTICIPANTS Participants ( N=305 ; age range , 65 - 93y ) recruited for a r and omized trial investigating the efficacy of a podiatry intervention to prevent falls . IN Output:	Conflicting evidence was found as to whether supervision of exercise improved adherence . Adherence to prescribed exercise in SpA was poorly reported and predominately for people with AS . The levels of adherence and factors affecting prescribed exercise in SpA remain unclear .
MS21205	*TASK* the task is to summarize an input biomedical literature in six sentences *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 field trial was conducted in the Gezira , Sudan , to evaluate the acceptability and efficacy of praziquantel , a new schistosomicide . In one Arab village 350 patients with Schistosoma mansoni were r and omly assigned to two treatment groups and given 1 X 40 mg kg-1 ( Group A ) or 2 X 20 mg kg-1 given four to six hours apart ( Group B ) . In two small settlements ( camps ) 2 km distant from the Arab village 38 patients with S. mansoni and 43 with concurrent S. mansoni and S. haematobium infections were given 1 X 40 mg kg-1 . Side effects were mild and limited to the first 24 hours after treatment . The main complaints were abdominal pain , diarrhoea , urticaria and /or vomiting and were most common in the camp residents ( 79 % ) with 60 % of Group A and 45 % of Group B having one or more side effects . One month after treatment ' cure ' rates were : Camps 63 % , Group A 84 % and Group B 96 % , and the reduction in egg output was over 95 % . After 12 months re-infection was greater in the camps . As there was no significant difference in the egg output reduction between the two treatment regimes , praziquantel is recommended for mass chemotherapy in Gezira at the logistically simpler regimen of 1 X 40 mg kg-1 Background The Schistosomiasis Consortium for Operational Research and Evaluation ( SCORE ) has launched several large-scale trials to determine the best strategies for gaining and sustaining control of schistosomiasis and transitioning toward elimination . In Côte d’Ivoire , a 5-year cluster-r and omized trial is being implemented in 75 schools to sustain the control of schistosomiasis mansoni . We report Schistosoma mansoni infection levels in children one year after the initial school-based treatment ( SBT ) with praziquantel and compare with baseline results to determine the effect of the intervention . Methodology The baseline cross-sectional survey was conducted in late 2011/early 2012 and the first follow-up in May 2013 . Three consecutive stool sample s were collected from 9- to 12-year-old children in 75 schools at baseline and 50 schools at follow-up . Stool sample s were subjected to duplicate Kato-Katz thick smears . Directly observed treatment ( DOT ) coverage of the SBT was assessed and the prevalence and intensity of S. mansoni infection compared between baseline and follow-up . Principal Findings The S. mansoni prevalence in the 75 schools surveyed at baseline was 22.1 % ( 95 % confidence interval ( CI ) : 19.5–24.4 % ) . The DOT coverage was 84.2 % . In the 50 schools surveyed at baseline and one year after treatment , the overall prevalence of S. mansoni infection decreased significantly from 19.7 % ( 95 % CI : 18.5–20.8 % ) to 12.8 % ( 95 % CI : 11.9–13.8 % ) , while the arithmetic mean S. mansoni eggs per gram of stool ( EPG ) among infected children slightly increased from 92.2 EPG ( 95 % CI : 79.2–105.3 EPG ) to 109.3 EPG ( 95 % CI : 82.7–135.9 EPG ) . In two of the 50 schools , the prevalence increased significantly , despite a DOT coverage of > 75 % . Conclusions / Significance One year after the initial SBT , the S. mansoni prevalence had decreased . Despite this positive trend , an increase was observed in some schools . Moreover , the infection intensity among S. mansoni-infected children was slightly higher at the 1-year follow-up compared to the baseline situation . Our results emphasize the heterogeneity of transmission dynamics and provide a benchmark for the future yearly follow-up surveys of this multi-year SCORE intervention study Integrated control strategies are important for sustainable control of schistosomiasis and soil-transmitted helminthiasis , despite their challenges for their effective implementation . With the support of Good Neighbors International in collaboration with National Institute of Medical Research , Mwanza , Tanzania , integrated control applying mass drug administration ( MDA ) , health education using PHAST , and improved safe water supply has been implemented on Kome Isl and over 5 years for controlling schistosomiasis and soil-transmitted helminths ( STHs ) . Baseline surveys for schistosomiasis and STHs was conducted before implementation of any integrated control strategies , followed by 4 cross-sectional follow-up surveys on r and omly selected sample s of schoolchildren and adults in 10 primary schools and 8 villages , respectively , on Kome isl and s. Those follow-up surveys were conducted for impact evaluation after introduction of control strategies interventions in the study area . Five rounds of MDA have been implemented from 2009 along with PHAST and improved water supply with pumped wells as other control strategies for complementing MDA . A remarkable steady decline of schistosomiasis and STHs was observed from 2009 to 2012 with significant trends in their prevalence decline , and thereafter infection rate has remained at a low sustainable control . By the third follow-up survey in 2012 , Schistosoma mansoni infection prevalence was reduced by 90.5 % and hookworm by 93.3 % among schoolchildren while in adults the corresponding reduction was 83.2 % and 56.9 % , respectively . Integrated control strategies have successfully reduced S. mansoni and STH infection status to a lower level . This study further suggests that monitoring and evaluation is a crucial component of any large-scale STH and schistosomiasis intervention Background In Mozambique , schistosomiasis is highly endemic across the whole country . The Schistosomiasis Consortium for Operational Research and Evaluation ( SCORE ) coordinates a five-year study that has been implemented in various African countries , including Mozambique . The overall goal of SCORE was to better underst and how to best apply preventive chemotherapy with praziquantel ( PZQ ) for schistosomiasis control by evaluating the impact of alternative treatment approaches . Methods This was a cluster-r and omised trial that compared the impact of different treatment strategies in study areas with prevalence among school children of ≥21 % S. haematobium infection by urine dipstick . Each village was r and omly allocated to one of six possible combinations of community-wide treatment ( CWT ) , school-based treatment ( SBT ) , and /or drug holidays over a period of four years , followed by final data collection in the fifth year . The most intense intervention arm involved four years of CWT , while the least intensive arm involved two years of SBT followed by two consecutive years of PZQ holiday . Each study arm included 25 villages r and omly assigned to one of the six treatment arms . The primary outcome of interest was change in prevalence and intensity of S. haematobium among 100 children aged 9-to-12-years that were sample d each year in every village . In addition to children aged 9-to-12 years , 100 children aged 5–8 years in their first-year of school and 50 adults ( aged 20–55 years ) were tested in the first and final fifth year of the study . Prevalence and intensity of S. haematobium infection was evaluated by two filtrations , each of 10mL , from a single urine specimen . Principal findings In total , data was collected from 81,167 individuals across 149 villages in ten districts of Cabo Delgado province , Northern Mozambique . Overall PZQ treatment result ed in a significant reduction in the prevalence of S. haematobium infection from Year 1 to Year 5 , where the average prevalence went from 60.5 % to 38.8 % , across all age groups and treatment arms . The proportion of those heavily infected also reduced from 17.6 % to 11.9 % over five years . There was a significantly higher likelihood of males being infected than females at baseline , but no significant difference between the sexes in their response to treatment . The only significant response based on a study arm was seen in both the 9-to-12-year-old and first-year cross sections , where two consecutive treatment holidays result ed in a significantly higher final prevalence of S. haematobium than no treatment holidays . When the arms were grouped together , four rounds of treatment ( regardless of whether it was CWT or SBT ) , however , did result in a significantly greater reduction in S. haematobium prevalence than two rounds of treatment ( i.e. with two intermittent or consecutive holiday years ) over a five-year period . Conclusions Although PC was successful in reducing the burden of active infection , even among those heavily infected , annual CWT did not have a significantly greater impact on disease prevalence or intensity than less intense treatment arms . This may be due to extremely high starting prevalence and intensity in the study area , with frequent exposure to reinfection , or related to challenges in achieving high treatment coverage More frequent treatment had a greater impact on prevalence and intensity of infection when arms were grouped by number of treatments , however , cost efficiency was greater in arms only receiving two treatments . Finally , a significant reduction in prevalence of S. haematobium was seen in adults even in the SBT arms implying the rate of transmission in the community had been decreased , even where only school children have been treated , which has significant logistical and cost-saving implication s for a national control programme in justifying CWT A parasitological , clinical and ultrasonographic longitudinal study was undertaken in 1993 in a focus hyperendemic for Schistosoma mansoni infection in the central highl and s of Madagascar . All the inhabitants were systematic ally treated with praziquantel . A complete examination and treatment were repeated each year . Among the 289 villagers who underwent the complete 3 years ' follow up , 65.9 % excreted eggs at the initial survey and the mean egg count of infected individuals was 202 eggs/g . In 1996 , the prevalence of infection was 19.3 % with a mean egg count of 27 eggs/g and , among inhabitants aged > 44 years , only one was found to be infected . The proportion of individuals complaining of bloody stool decreased from 24.9 % in 1993 to 8.4 % in 1996 . Compared to the initial clinical examination , the age-adjusted prevalence of splenomegaly was significantly lower in 1996 , but remained high : 62 % in the 10 - 14 years age group and 59 % in individuals aged > 24 years . Ultrasonographic examination after 3 years of praziquantel therapy showed a marked decrease of the overall prevalence of schistosomal hepatic fibrosis , from 28 % in 1993 to 10.3 % in 1996 . This improvement had already been achieved during the second year of follow-up for most subjects . Usually , the reversal of morbidity affected individuals classified as stage 1 at the beginning of the study . Stage 3 was not observed in the last 2 surveys . One patient 's ascites disappeared during the follow-up , associated with a significant reversal of periportal fibrosis . Our results indicate that repeated praziquantel therapy can lead to improvement of liver morbidity and the prevention of the development of schistosomal hepatic fibrosis , even in an old-established hyperendemic focus OBJECTIVE In the course of performing systematic review s on the prevalence of low back and neck pain , we required a tool to assess the risk of study bias . Our objectives were to ( 1 ) modify an existing checklist and ( 2 ) test the final tool for interrater agreement . STUDY DESIGN AND SETTING The final tool consists of 10 items addressing four domains of bias plus a summary risk of bias assessment . Two research ers tested the interrater agreement of the tool by independently assessing 54 r and omly selected studies . Interrater agreement overall and for each individual item was assessed using the proportion of agreement and Kappa statistic . RESULTS Raters found the tool easy to use , and there was high interrater agreement : overall agreement was 91 % and the Kappa statistic was 0.82 ( 95 % confidence interval : 0.76 , 0.86 ) . Agreement was almost perfect for the individual items on the tool and moderate for the summary assessment . CONCLUSION We have addressed a research gap by modifying and testing a tool to assess risk of study bias . Further research may be useful for assessing the applicability of the tool across different conditions BACKGROUND In sub-Saharan Africa , 112 million people are infected with Schistosoma haematobium , with the most intense infections in children 5 - 15 years old . METHODS We describe a longitudinal epidemiological study that evaluates the relationship between S. haematobium infection and associated morbidity in children before and after the large-scale administration of praziquantel for schistosomiasis and albendazole for soil-transmitted helminths . RESULTS At baseline , higher intensities of S. haematobium infection were observed in children with anemia and /or severe microhematuria , but there was no apparent association between the risk of undernutrition and intensity of S. haematobium infection . Significant reductions in the prevalence and intensity of S. haematobium infection 1 year after treatment were , however , observed . Children who benefited the most from anthelmintic treatment in terms of increased hemoglobin concentrations were those who had anemia at baseline and those with highly positive microhematuria scores at baseline . CONCLUSIONS This study suggests that even a single round of mass chemotherapy can have a substantial impact on S. haematobium infection and its associated morbidity in children Although it is established that the treatment by praziquantel reduces the Output:	Box plots also showed no apparent differences in intensity reduction between the two treatment strategies . / SIGNIFICANCE The results of this meta- analysis do not support the hypothesis that community-wide treatment is more effective than targeted treatment at reducing schistosomiasis infections in children .
MS21206	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: An open field trial was conducted comparing desipramine and an active placebo in separate population s of chronic cocaine and phencyclidine ( PCP ) abusers , who discontinued their abuse . Subjects who received desipramine showed a decrease in depressive symptoms after a 20 - 40 day period regardless of whether they abused PCP or cocaine BACKGROUND The N-methyl-d-aspartate receptor antagonist ketamine has rapid antidepressant effects in major depression . Psychotomimetic symptoms , dissociation and hemodynamic changes are known side effects of ketamine , but it is unclear if these side effects relate to its antidepressant efficacy . METHODS Data from 108 treatment-resistant in patients meeting criteria for major depressive disorder and bipolar disorder who received a single subanesthetic ketamine infusion were analyzed . Pearson correlations were performed to examine potential associations between rapid changes in dissociation and psychotomimesis with the Clinician-Administered Dissociative States Scale ( CADSS ) and Brief Psychiatric Rating Scale ( BPRS ) , respectively , manic symptoms with Young Mania Rating Scale ( YMRS ) , and vital sign changes , with percent change in the 17-item Hamilton Depression Rating scale ( HDRS ) at 40 and 230min and Days 1 and 7 . RESULTS Pearson correlations showed significant association between increased CADSS score at 40min and percent improvement with ketamine in HDRS at 230min ( r=-0.35 , p=0.007 ) and Day 7 ( r=-0.41 , p=0.01 ) . Changes in YMRS or BPRS Positive Symptom score at 40min were not significantly correlated with percent HDRS improvement at any time point with ketamine . Changes in systolic blood pressure , diastolic blood pressure , and pulse were also not significantly related to HDRS change . LIMITATIONS Secondary data analysis , combined diagnostic groups , potential unblinding . CONCLUSIONS Among the examined mediators of ketamine׳s antidepressant response , only dissociative side effects predicted a more robust and sustained antidepressant . Prospect i ve , mechanistic investigations are critically needed to underst and why intra-infusion dissociation correlates with a more robust antidepressant efficacy of ketamine BACKGROUND Although significant evidence suggests that diminished monoamine function is associated with clinical depression , catecholamine or indoleamine depletion alone has not been associated with significant mood changes in unmedicated depressed subjects or never-depressed control subjects . This study assesses the integrated role of these monoamine systems in depressed patients . METHODS Unmedicated depressed subjects underwent a 2-week , double-blind , r and om-ordered crossover study consisting of the following active and control conditions respectively : indoleamine ( via tryptophan depletion ) plus catecholamine ( via alpha-methyl-paratyrosine administration ) depletion and , separately , indoleamine plus sham ( via diphenhydramine administration ) catecholamine depletion . Ten subjects completed both conditions ; two subjects were withdrawn after active testing and one after control testing . RESULTS Mean Hamilton Depression Rating Scale ( HDRS ) scores decreased progressively throughout the study days ( baseline 26.7 points + /- 1.7 SEM and termination 20.0 + /- 2.4 , active depletion ; baseline 26.1 points + /- 2.3 SEM and termination 23.2 + /- 2.6 , control testing ) but did not differ between groups . Only three patients demonstrated 20 % or greater increases from baseline HDRS at any point during the observation days . CONCLUSIONS Overall , results show that simultaneous disruptions of indoleamine and catecholamine function do not exacerbate symptoms in unmedicated depressed subjects , thus lending further support to the notion that monoamines regulate mood in actively depressed patients via indirect mechanisms A sample of placebo-controlled tricyclic antidepressant studies was examined retrospectively to determine whether there was any difference in the relative efficacy of the tricyclic when it was compared against an inert placebo as against an active ( atropine ) placebo with anticholinergic side effects . Fewer studies showed a significant difference between atropine placebo and drug than between inert placebo and drug . The possibilities that atropine has a specific antidepressant effect , or that side effects amplify placebo responses are considered BACKGROUND Although hypotheses about the therapeutic mechanism of action of light therapy have focused on serotonergic mechanisms , the potential role , if any , of catecholaminergic pathways has not been fully explored . METHODS Sixteen patients with seasonal affective disorder who had responded to a st and ard regimen of daily 10000-lux light therapy were enrolled in a double-blind , placebo-controlled , r and omized crossover study . We compared the effects of tryptophan depletion with catecholamine depletion and sham depletion . Ingestion of a tryptophan-free amino acid beverage plus amino acid capsules was used to deplete tryptophan . Administration of the tyrosine hydroxylase inhibitor alpha-methyl-paratyrosine was used to deplete catecholamines . Diphenhydramine hydrochloride was used as an active placebo during sham depletion . The effects of these interventions were evaluated with measures of depression , plasma tryptophan levels , and plasma catecholamine metabolites . RESULTS Tryptophan depletion significantly decreased plasma total and free tryptophan levels . Catecholamine depletion significantly decreased plasma 3-methoxy-4-hydroxyphenylethyleneglycol and homovanillic acid levels . Both tryptophan depletion and catecholamine depletion , compared with sham depletion , induced a robust increase ( P<.001 , repeated- measures analysis of variance ) in depressive symptoms as measured with the Hamilton Depression Rating Scale , Seasonal Affective Disorder Version . CONCLUSIONS The beneficial effects of light therapy in the treatment of seasonal affective disorder are reversed by both tryptophan depletion and catecholamine depletion . These findings confirm previous work showing that serotonin plays an important role in the mechanism of action of light therapy and provide new evidence that brain catecholaminergic systems may also be involved OBJECTIVE Ketamine , a glutamate N-methyl-d-aspartate ( NMDA ) receptor antagonist , has shown rapid antidepressant effects , but small study groups and inadequate control conditions in prior studies have precluded a definitive conclusion . The authors evaluated the rapid antidepressant efficacy of ketamine in a large group of patients with treatment-resistant major depression . METHOD This was a two-site , parallel-arm , r and omized controlled trial of a single infusion of ketamine compared to an active placebo control condition , the anesthetic midazolam . Patients with treatment-resistant major depression experiencing a major depressive episode were r and omly assigned under double-blind conditions to receive a single intravenous infusion of ketamine or midazolam in a 2:1 ratio ( N=73 ) . The primary outcome was change in depression severity 24 hours after drug administration , as assessed by the Montgomery-Åsberg Depression Rating Scale ( MADRS ) . RESULTS The ketamine group had greater improvement in the MADRS score than the midazolam group 24 hours after treatment . After adjustment for baseline scores and site , the MADRS score was lower in the ketamine group than in the midazolam group by 7.95 points ( 95 % confidence interval [ CI ] , 3.20 to 12.71 ) . The likelihood of response at 24 hours was greater with ketamine than with midazolam ( odds ratio , 2.18 ; 95 % CI , 1.21 to 4.14 ) , with response rates of 64 % and 28 % , respectively . CONCLUSIONS Ketamine demonstrated rapid antidepressant effects in an optimized study design , further supporting NMDA receptor modulation as a novel mechanism for accelerated improvement in severe and chronic forms of depression . More information on response durability and safety is required before implementation in clinical practice The mechanism of action of electroconvulsive therapy ( ECT ) in treating major depression is unknown . We studied two c and i date mechanisms through inhibiting simultaneously the synthesis of noradrenaline and serotonin in patients immediately after successful treatment with ECT using a r and omised , placebo-controlled , double-blind crossover design . There were no significant changes in depression scores under any experimental conditions , or between the amine-depleted and placebo groups despite reductions of 61 % in serum homovanillic acid , 47 % in 3-methoxy-4-hydroxyenylethyleneglycol , and 89 % in serum tryptophan . Catecholamine and serotonin availability may not be necessary for maintaining the initial antidepressant response to ECT Psychopharmacological studies usually attempt to eliminate " nonspecific " influences on outcome by double-blind design s. In a r and omized , double-blind comparison of alprazolam , imipramine , and placebo , the great majority of panic disorder patients ( N = 59 ) and their physicians were able to rate accurately whether active drug or placebo had been given . Moreover , physicians could distinguish between the two types of active drugs . Inasmuch as correct rating was possible halfway through treatment , concerns about the internal validity of the double-blind strategy arise TOC summary The 50 % likelihood of receiving a drug or placebo in clinical trials modifies the outcome , an effect strongly modulated if minor onset sensations are associated with drug intake . ABSTRACT The knowledge of having only a 50 % chance of receiving an active drug can result in reduced efficacy in blinded r and omized clinical trials ( RCTs ) compared to clinical practice ( reduced external validity ) . Moreover , minor onset sensations associated with the drug ( but not with an inert placebo ) can further challenge the attribution of group differences to drug‐specific efficacy ( internal validity ) . We used a r and omized experimental study with inert placebos ( inert substance ) vs active placebos ( inducing minor sensations ) , and different instructions about group allocation ( probability of receiving drug : 0 % , 50 % , 100 % ) . One hundred forty‐four healthy volunteers were informed that a new application method for a well‐known painkiller would be tested . Pain thresholds were assessed before and after receiving nasal spray . Half of the nasal sprays were inert placebos ( sesame oil ) , while the other half were active placebos inducing prickling nasal sensations ( sesame oil with 0.014 % capsaicin ) . The major outcome was pain threshold after placebo application . A substantial expectation effect was found for the inert placebo condition , with participants who believed they had received an active drug reporting the highest pain thresholds . Active placebos show substantial differences to passive placebos in the 50 % chance group . Therefore , patient expectations are significantly different in placebo‐controlled clinical trials ( 50 % chance ) vs clinical practice ( 100 % chance ) . Moreover , minor drug onset sensations can challenge internal validity . Effect sizes for these mechanisms are medium , and can substantially compete with specific drug effects . For clinical trials , new study design s are needed that better control for these effects As part of a study of drug treatment of aggressive behavior to be reported separately , we have evaluated the double‐blind procedure in a recently completed comparison of the efficacy of lithium carbonate versus placebo in modifying aggressive behavior in nonpsychotic incarcerated delinquents . We conclude that the side effects of lithium carbonate are sufficient to reveal the medication to most subjects receiving it . Thus , while the study staff could not identify lithium‐receivers at better than chance levels , and while subjects who received placebo could not identify their medication at better than chance levels , subjects who received lithium could accurately identify it . On a weekly symptom check list there was no difference between lithium and placebo groups on average lithium target symptoms reported during 4‐week pre‐ and postmedication control periods ; however , lithium‐receivers reported significantly more target symptoms every week medication was administered . Of 16 subjects who quit the study , 14 had received lithium and nearly all of those who gave reasons for quitting specified side effects , most often nausea . The method ological problems of using lithium in a double‐blind design might be overcome by employing a “ discontinuation ” design , or , speculatively , a double‐blind , cross‐over design utilizing an “ active placebo ” Objective : Although antidepressants are widely prescribed as analgesics in chronic back pain , their clinical pharmacology is not well established . Norepinephrine transporter blockade seems to be essential for analgesia , but optimal concentrations are unknown . Fixed-dose studies of serotonin reuptake inhibitors are generally negative , but such studies can not be interpreted clearly because efficacy might be detected if concentration-response relationships were known . We evaluated ( 1 ) the feasibility of conducting a controlled-concentration study of a norepinephrine ( desipramine ) and a serotonin reuptake ( fluoxetine ) inhibitor and ( 2 ) the relationship between achieved concentrations and analgesic response . Methods : This single-center , 12-week , double-blind , prospect i ve , controlled-concentration study r and omized 121 chronic back pain patients without major depression to active placebo ( benztropine mesylate ) or to predetermined low , medium , or high concentrations of desipramine ( targets were 50 , 110 , and Output:	The use of active placebos was clustered in specific research setting s and did not appear to reflect consistently the side effect profile of the experimental intervention , for example , selective serotonin reuptake inhibitors were compared with active placebos in pain trials but not in depression trials . The main argument for active placebo was to reduce risk of unblinding ; the main argument against was the risk of unintended therapeutic effect . Pharmacological active placebo control interventions are rarely used in r and omized clinical trials , but they constitute a method ological tool which merits serious consideration . We suggest that active placebos are used more often in trials of drugs with noticeable side effects , especially in situations where the expected therapeutic effects are modest and the risk of bias due to unblinding is high
MS21207	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: In a prospect i ve , r and omized study , 30 patients were evaluated after ankle fracture treated by means of open reduction and internal fixation . The patients were r and omized to either postoperative immobilization in a plaster cast for 6 weeks or early mobilization ( 1–2 weeks after surgery ) in an ankle brace . Both regimens allowed weightbearing . Evaluation after 10 weeks and after 12 months included clinical assessment and isokinetic muscle strength measurements . Patients with impaired ankle function , as shown by means of an ankle score at 12 months , were followed for 3 years . At 10 weeks , impaired muscle torque and restricted range of motion was found on the affected side . This impairment was significantly less in the brace group . At 12 months , range of motion of the ankle and subtalar joints was restored , but dorsiflexion was still better in the brace group . Score values from a functional score did not correlate with muscle strength The effect of early mobilization and unrestricted weight bearing on final ankle motion in 51 operatively stabilized ankle fractures was prospect ively investigated . Patients were treated with an ankle-foot orthosis ( AFO ) or a cast . Full weight bearing was unrestricted in both groups . Thirty-two fractures received an AFO and 19 received a cast . The follow-up period ranged from 2.3 to 66 months , with a median of eight months . At the final follow-up examination , the motion in the AFO-treated group was not functionally different from that of the cast-treated group . However , 72 % of the patients treated in an AFO compared with 37 % of patients treated in a cast had ankle dorsiflexion greater than 15 degrees ( p = 0.014 ) . No complications were directly related to the AFO . No loss of reduction occurred in any patient . The results of this series indicate that early motion of a fractured ankle treated operatively does not affect ankle motion . Early motion was not associated with increased morbidity or loss of reduction We r and omised prospect ively 60 consecutive patients who were undergoing internal fixation of similar fractures of the ankle into two groups , one of which was treated by immobilisation in a below-knee cast and the other by a functional brace with early movement . All were instructed to avoid weight-bearing on the affected side . They were seen at 6 , 12 , 26 and 52 weeks . The functional rating scale of Mazur et al was used to evaluate the patients at each follow-up and we recorded the time of return to work . After one year the patients completed the SF-36 question naire . By then 55 patients remained in the study , 28 ( mean age 45.5 years ) in group 1 and 27 ( mean age 39.5 years ) in group 2 . Those in group 2 had higher functional scores at each follow-up but only at six weeks was this difference significant ( p = 0.02 ) . They also had higher mean SF-36 scores , but this difference was significant only for two of the eight aspects investigated . For patients gainfully employed , not on workers ' compensation , the mean time from surgery to return to work was 53.3 days for group 2 and 106.5 days for group 1 ; this difference was significant ( p = 0.01 ) . No patient developed a problem with the wound or had loss of fixation . Our findings support the use of a functional brace and early movement after surgery for fractures of the ankle Fifty-three patients with dislocated lateral malleolar fractures were r and omly selected after operation for either active ankle movement and weight bearing in an orthosis or no ankle movement but weight bearing in a walking cast . At follow-up examinations after three , six , and 18 months , no differences were found between the groups except for a better linear analogue scale result at three months for the orthosis group . Active ankle movements do not improve the rehabilitation of surgically treated lateral malleolar fractures In a prospect i ve , r and omised study , 27 patients with internally fixed ankle fractures were treated post-operatively for a period of six weeks by application of either a new dynamic vacuum orthosis with permitted mobilisation to 10 ° –0 ° –10 ° at the ankle joint or a synthetic cast . Full weight bearing was allowed in both groups after two weeks . The cast group was prescribed four weeks of physiotherapy following six weeks of immobilisation . After ten weeks , the Olerud and Mol and er score showed a significant difference in favour of the orthosis . Early functional outcomes were significantly better for this group after six weeks and ten weeks . Patients in the orthosis group who were in formal employment returned to work 24 days earlier than those in the control group . Treatment of the orthosis patients took up three to four times less working time for the medical personnel . A saving of 38 euros on directly ascertainable costs could be evaluated . Rehabilitation of ankle fractures with a dynamic vacuum orthosis leads to better early functional results and greater patient satisfaction . The orthosis fulfils the conditions for early return to work . Treatment with an orthosis not only reduces working time for medical personnel but economises on expenditure for treatment and rehabilitation . RésuméUne étude r and omisée a été réalisée chez 27 patients présentant une fracture de la cheville et traités sur une période de six semaines soit par une orthèse dynamique permettant une mobilisation de 10 ° dans chaque secteur soit par une immobilisation plâtrée . Une marche avec appui complet a été autorisée dans les deux groupes , après 15 jours . Le groupe des patients plâtrés a bénéficié de 4 semaines de rééducation après six semaines d’immobilisation . Après 10 semaines , le score d’Olerud et de Mol and er montre une différence significative dans les résultats en faveur de l’orthèse . En effet , le devenir fonctionnel de ces patients a été de façon significative bien meilleur pour ce groupe après six semaines et après dix semaines . Ces patients sont retournés au travail 24 jours plus tôt que dans le groupe contrôle . Le traitement par orthèse permet d’économiser 38 euros et du temps médical . La rééducation de la fracture des chevilles grâce à l’orthèse dynamique permet un résultat fonctionnel excellent et relativement rapide . Cette orthèse met les patients dans de bonnes conditions pour un retour précoce à l’emploi , ce traitement permet également d’économiser le travail des médecins et permet également de faire des économies sur le temps de rééducation BACKGROUND AND PURPOSE The goal of this investigation was to study the recovery of ankle plantar-flexor peak torque , fatigue resistance , and functional ability ( stair climbing , walking ) following cast immobilization in patients with ankle fractures . SUBJECTS The participants were 10 patients who underwent open reduction-internal fixation and 8 weeks of cast immobilization following a fracture of the ankle mortise and 10 age- and sex-matched , noninjured comparison subjects . METHODS Plantar-flexor torque and fatigue resistance were measured at 1 , 5 , and 10 weeks of rehabilitation using an isokinetic dynamometer . Ankle plantar-flexor peak torque and fatigue resistance were correlated to timed ambulation , timed stair climbing , and unilateral heel-rises . RESULTS Following immobilization , plantar-flexor peak torque was decreased at all angular speeds and positions . The decrease in peak torque was associated with an increase in fatigue resistance . With rehabilitation , ankle plantar-flexor torque and fatigue resistance normalized . Regression analysis revealed a strong relationship between plantar-flexor peak torque and functional measures . By 10 weeks post-immobilization , peak torque , fatigue resistance , and all measures of functional performance had returned to control levels . CONCLUSION AND DISCUSSION The decrease in muscle performance , functional ability , and fatigue resistance induced by 8 weeks of cast immobilization can be reversed with 10 weeks of supervised physical therapy . In addition , this study demonstrated that ankle-plantar flexor torque is a good predictor of stair-climbing and walking performance in patients with ankle fractures Background : The aim of operative treatment for ankle fractures is to allow early movement after internal fixation . The hypothesis of this study was that early mobilization would improve functional recovery in patients after surgery for ankle fractures . Methods : In a prospect i ve r and omized controlled study , 66 consecutive patients with ankle fractures that required open reduction and internal fixation ( ORIF ) were assigned to one of two postoperative regimens : immobilization in a nonweightbearing below-knee cast or early mobilization in a removable cast . Four patients were excluded from the study , leaving 62 for review . Results : Patients who had early mobilization in a removable cast had higher functional scores ( Olerud-Mol and er and AOFAS ) at 9 and 12 weeks postoperatively . They also returned to work earlier ( 67 days ) compared with those treated in nonweightbearing below-knee cast ( 95 days ) , p < 0.05 . There was no statistical difference in Quality of Life ( SF-36 Question naire ) at 6 months between the two groups . We had an approximately 10 % postoperative infection trend ( one superficial and two deep ) in the early mobilization group . Conclusion : Despite the overall short-term benefit of early mobilization , we had three patients in the early mobilization group who had wound complications . Both the surgeon and patient should be aware of the higher risk of wound complications associated with this treatment , and thus the accelerated rehabilitation protocol should be individualized In a prospect i ve r and omized trial the early functional results after immobilisation in a cast were compared to those after using a vacuum stabilizing system . The vacuum stabilizing system Vacoped offers equivalent stability compared to a plaster cast . In contrast to the cast the Vacoped can be removed for body care and physical therapy . Additionally the range of motion for dorsal flexion/extention in the upper ankle joint can be adjusted . From 9/1996 to 7/1997 there were 40 patients included in the study with an operated ankle fracture as monotrauma . Six weeks postoperatively the patients with cast treatment showed significantly higher functional deficits for the upper ankle joint ( 20 % ) , the lower ankle joint ( 40 % ) and muscle atrophy ( 2.1 cm side difference ) than the group with the vacuum stabilizing system ( upper ankle joint 15 % , lower ankle joint 25 % , 1.4 cm muscle atrophy ) . Five patients out of the group with the vacuum system were already at work three weeks postoperatively . Three months postoperatively the functional results for both groups were approximating . The vacuum stabilizing system Vacoped offers better early functional results than conventional cast treatment after osteo synthesis of ankle fractures . Because of the increased patient comfort and the early ability for physical therapy the vacuum stabilizing system is preferable to cast treatment Fifty-six patients who had a displaced fracture of the ankle necessitating surgical fixation were r and omly assigned to one of three postoperative treatment regimens : no plaster cast or weight-bearing , and active exercises of the ankle ; a non-weight-bearing plaster cast ; or a plaster walking cast for the first six postoperative weeks . At follow-up with a duration of as much as two years , there were no consistent differences in the clinical results between the three groups . The time lost from work and the proportion of excellent and good clinical results were also uninfluenced by the postoperative regimen . No adverse effects could be detected as a result of the patient 's having walked before the syndesmosis screw had been removed . It was concluded that none of the three postoperative regimens has any advantage over the others in a patient who has a stable osteo synthesis of a fracture of the ankle Background : Controversy continues with regard to the optimal postoperative care after open reduction and internal fixation of an ankle fracture . The hypothesis of this study was that postoperative treatment of an ankle fracture with a brace that allows active and passive range-of-motion exercises would improve the functional recovery of patients compared with that after conventional treatment with a cast . Thus , the purpose of this prospect i ve , r and omized study was to compare the long-term subjective , objective , and functional outcome after conventional treatment with a cast and that after use of functional bracing in the first six weeks following internal fixation of an ankle fracture . Methods : One hundred patients with an unstable and /or displaced Weber type-A or B ankle fracture were treated operatively and then were r and omly allocated to two groups : immobilization in a below-the-knee cast ( fifty patients ) or early mobilization in a functional ankle brace ( fifty patients ) for the first six postoperative weeks . The follow-up examinations , which consisted of subjective and objective ( clinical , radiographic , and functional ) evaluations , were performed at two , six , twelve , and fifty-two weeks and at two years postoperatively . Results : There were no perioperative complications in either study group , but eight patients who were managed with a cast and thirty-three patients who were managed with a brace had postoperative complications , which were mainly related to wound-healing . Two patients in the group treated with a cast had deep-vein thrombosis . All fractures healed well in both groups . The difference between the two groups with respect to the complication rate was significant ( p = 0.0005 ) . No significant differences between the study groups were observed in the final subjective or objective ( clinical ) evaluation . At the two-year follow-up examination , the average score ( and st and ard deviation ) according to the ankle-rating scale of Kaikkonen et al. was 85 ± 9 points for the group treated with a cast and 83 ± 10 points for the group treated with a brace , and the average ankle score according to the system of Olerud and Mol and er was 87 ± 8 points and 87 ± 9 points , respectively . Conclusions : The long-term functional outcome Output:	Deep surgical site infection ( Peto odds ratio = 7.08 ; 95 % confidence interval : 1.39 , 35.99 ; P = .02 ; I(2 ) = 0 % ) , superficial surgical site infection , fixation failure , and reoperation to remove metalwork were more common after early ankle movement compared to immobilization . The effects of early movement after ankle surgery on short-term functional outcomes are unclear , but there is no observable difference in the longer term . There is a small reduction in risk of postoperative thromboembolism with early ankle movement . Current evidence suggests that deep and superficial surgical site infections , fixation failure , and the need to remove metalwork are more common after early ankle movement .
MS21208	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Although melatonin and cognitive-behavioural therapy have shown efficacy in treating sleep disorders in children with autism spectrum disorders , little is known about their relative or combined efficacy . One hundred and sixty children with autism spectrum disorders , aged 4 - 10 years , suffering from sleep onset insomnia and impaired sleep maintenance , were assigned r and omly to either ( 1 ) combination of controlled-release melatonin and cognitive-behavioural therapy ; ( 2 ) controlled-release melatonin ; ( 3 ) four sessions of cognitive-behavioural therapy ; or ( 4 ) placebo drug treatment condition for 12 weeks in a 1 : 1 : 1 : 1 ratio . Children were studied at baseline and after 12 weeks of treatment . Treatment response was assessed with 1-week actigraphic monitoring , sleep diary and sleep question naire . Main outcome measures , derived actigraphically , were sleep latency , total sleep time , wake after sleep onset and number of awakenings . The active treatment groups all result ed in improvements across all outcome measures , with moderate-to-large effect sizes from baseline to a 12-week assessment . Melatonin treatment was mainly effective in reducing insomnia symptoms , while cognitive-behavioural therapy had a light positive impact mainly on sleep latency , suggesting that some behavioural aspects might play a role in determining initial insomnia . The combination treatment group showed a trend to outperform other active treatment groups , with fewer dropouts and a greater proportion of treatment responders achieving clinical ly significant changes ( 63.38 % normative sleep efficiency criterion of > 85 % and 84.62 % , sleep onset latency < 30 min ) . This study demonstrates that adding behavioural intervention to melatonin treatment seems to result in a better treatment response , at least in the short term BACKGROUND Children with high-functioning autism spectrum disorders ( ASD ) are at high risk for developing significant anxiety . Anxiety can adversely impact functioning across school , home and community environments . Cognitive behavioral therapies ( CBT ) are frequently used with success for children with anxiety symptoms . Modified CBT interventions for anxiety in children with ASD have also yielded promising results . METHODS Fifty children with high-functioning ASD and anxiety were r and omizedto group CBT or treatment-as-usual ( TAU ) for 12 weeks . Independent clinical evaluators , blind to condition , completed structured interviews ( Anxiety Disorders Interview Schedule – Parent Version;ADIS-P ) pre- and post-intervention condition . RESULTS Forty-seven children completed either the CBT or TAU condition . Results indicated markedly better outcomes for the CBT group . Significant differences by group were noted in Clinician Severity Ratings , diagnostic status , and clinician ratings of global improvement . In the intent-to-treat sample , 10 of 20 children ( 50 % ) in the CBT group had a clinical ly meaningful positive treatment response , compared to 2 of 23 children ( 8.7 % ) in the TAU group . CONCLUSIONS Initial results from this r and omized , design ed treatment study suggest that agroup CBT intervention specifically developed for children with ASD may be effective in decreasing anxiety . Limitations of this study include small sample size , lack of an attention control group , and use of outcome measures normed with typically developing OBJECTIVE Better Nights/Better Days , a distance intervention for insomnia in school-aged children ( with and without attention-deficit/hyperactivity disorder [ ADHD ] ) , was evaluated to determine its effectiveness on children 's sleep and psychosocial functioning . METHODS A single center , parallel group design r and omized controlled trial ( stratified on ADHD diagnosis ) was conducted . Parents were r and omized to intervention ( n = 31 ) or waitlist control ( n = 30 ) , and completed question naires administered over the phone at baseline , postintervention ( 2 months ) , and follow-up ( 6 months ) . Actigraphy was also collected . The intervention consisted of a five-session manual and weekly telephone coach support . RESULTS The intervention group demonstrated a significant reduction in sleep problems and improved psychosocial functioning at postintervention and follow-up . Actigraphy results indicated improved sleep onset , but not sleep duration . Children with and without ADHD responded in a similar manner to this intervention . Parents provided high satisfaction ratings . CONCLUSIONS This intervention holds promise as an accessible , sustainable , and effective program to address insomnia in school-aged children Objective To examine whether behavioural strategies design ed to improve children ’s sleep problems could also improve the symptoms , behaviour , daily functioning , and working memory of children with attention deficit hyperactivity disorder ( ADHD ) and the mental health of their parents . Design R and omised controlled trial . Setting 21 general paediatric practice s in Victoria , Australia . Participants 244 children aged 5 - 12 years with ADHD attending the practice s between 2010 and 2012 . Intervention Sleep hygiene practice s and st and ardised behavioural strategies delivered by trained psychologists or trainee paediatricians during two fortnightly consultations and a follow-up telephone call . Children in the control group received usual clinical care . Main outcome measures At three and six months after r and omisation : severity of ADHD symptoms ( parent and teacher ADHD rating scale IV— primary outcome ) , sleep problems ( parent reported severity , children ’s sleep habits question naire , actigraphy ) , behaviour ( strengths and difficulties question naire ) , quality of life ( pediatric quality of life inventory 4.0 ) , daily functioning ( daily parent rating of evening and morning behavior ) , working memory ( working memory test battery for children , six months only ) , and parent mental health ( depression anxiety stress scales ) . Results Intervention compared with control families reported a greater decrease in ADHD symptoms at three and six months ( adjusted mean difference for change in symptom severity −2.9 , 95 % confidence interval −5.5 to −0.3 , P=0.03 , effect size −0.3 , and −3.7 , −6.1 to −1.2 , P=0.004 , effect size −0.4 , respectively ) . Compared with control children , intervention children had fewer moderate-severe sleep problems at three months ( 56 % v 30 % ; adjusted odds ratio 0.30 , 95 % confidence interval 0.16 to 0.59 ; P<0.001 ) and six months ( 46 % v 34 % ; 0.58 , 0.32 to 1.0 ; P=0.07 ) . At three months this equated to a reduction in absolute risk of 25.7 % ( 95 % confidence interval 14.1 % to 37.3 % ) and an estimated number needed to treat of 3.9 . At six months the number needed to treat was 7.8 . Approximately a half to one third of the beneficial effect of the intervention on ADHD symptoms was mediated through improved sleep , at three and six months , respectively . Intervention families reported greater improvements in all other child and family outcomes except parental mental health . Teachers reported improved behaviour of the children at three and six months . Working memory ( backwards digit recall ) was higher in the intervention children compared with control children at six months . Daily sleep duration measured by actigraphy tended to be higher in the intervention children at three months ( mean difference 10.9 minutes , 95 % confidence interval −19.0 to 40.8 minutes , effect size 0.2 ) and six months ( 9.9 minutes , −16.3 to 36.1 minutes , effect size 0.3 ) ; however , this measure was only completed by a subset of children ( n=54 at three months and n=37 at six months ) . Conclusions A brief behavioural sleep intervention modestly improves the severity of ADHD symptoms in a community sample of children with ADHD , most of whom were taking stimulant medications . The intervention also improved the children ’s sleep , behaviour , quality of life , and functioning , with most benefits sustained to six months post-intervention . The intervention may be suitable for use in primary and secondary care . Trial registration Current Controlled Trials IS RCT N68819261 OBJECTIVE Sleep difficulties are common reasons why parents seek medical intervention in children with autism spectrum disorders ( ASDs ) . We determined whether a pamphlet alone could be used by parents to help their child ’s insomnia . METHODS Thirty-six children with ASD , ages 2 to 10 years , were enrolled . All had prolonged sleep latency confirmed by actigraphy showing a mean sleep latency of 30 minutes or more . Parents were r and omly assigned to receive the sleep education pamphlet or no intervention . Children wore an actigraphy device to record baseline sleep parameters , with the primary outcome variable being change in sleep latency . Actigraphy data were collected a second time 2 weeks after the parent received the r and omization assignment and analyzed by using Student ’s t test . Parents were also asked a series of questions to gather information about the pamphlet and its usefulness . RESULTS Although participants r and omized to the 2 arms did not differ statistically in age , gender , socioeconomic status , total Children ’s Sleep Habits Question naire score , or actigraphy parameters , some differences may be large enough to affect results . Mean change in sleep-onset latency did not differ between the r and omized groups ( pamphlet versus no pamphlet ) . Parents commented that the pamphlet contained good information , but indicated that it would have been more useful to be given specific examples of how to take the information and put it into practice . CONCLUSIONS A sleep education pamphlet did not appear to improve sleep latency in children with ASDs Background : Settling and night waking problems are particularly prevalent , persistent , and generally considered difficult to treat in children with a learning disability , although intervention trials are few . Scarce re sources , however , limit access to proven behavioural treatments . Aims : To investigate the efficacy of a media based brief behavioural treatment of sleep problems in such children by comparing ( 1 ) face-to-face delivered treatment versus control and ( 2 ) booklet delivered treatment versus controls . Methods : The parents of 66 severely learning disabled children aged 2–8 years with settling and /or night waking problems took part in a r and omised controlled trial with a wait-list control group . Behavioural treatments were presented either conventionally face-to-face or by means of a 14 page easy to read illustrated booklet . A composite sleep disturbance score was derived from sleep diaries kept by parents . Results : Both forms of treatment were almost equally effective compared with controls . Two thirds of children who were taking over 30 minutes to settle five or more times per week and waking at night for over 30 minutes four or more times per week improved on average to having such settling or night waking problems for only a few minutes or only once or twice per week ( H = 34.174 , df = 2 , p<0.001 ) . These improvements were maintained after six months . Conclusions : Booklet delivered behavioural treatments for sleep problems were as effective as face-to-face treatment for most children in this population Abstract Objectives . We tested the hypothesis that sleep training would improve emotional , social and behavioural functioning in children with attention-deficit/hyperactivity disorder ( ADHD ) compared to children with ADHD without such intervention and to healthy controls . Methods . Forty children with ADHD were r and omly assigned to intervention and control conditions . Parents of 20 children with ADHD were instructed and thoroughly supervised in improving their children 's sleep schedules and sleep behaviour . Parents of the other 20 children with ADHD and parents of 20 healthy children received general information about sleep hygiene . At baseline and 12 weeks later , parents and children completed question naires related to children 's sleep and psychological functioning . Results . Relative to the control groups , children in the intervention group improved sleep quantitatively and qualitatively ( F values < 3.33 , P values < 0.05 ) . The intervention group children reported improvements in mood , emotions , and relationships ( F values < 2.99 , P values < 0.05 ) . Parents reported that their children improved in physical and psychological wellbeing , mood , emotions , relationships , and social acceptance ( F values < 3.02 , P values < 0.05 ) . Conclusions . Training and monitoring parents of children with ADHD in regulating and supervising children 's sleep schedules leads to positive changes in the emotions , behaviour and social lives of these children OBJECTIVE To examine associations between sleep problems during development and subsequent emotional and behavioral difficulties . DESIGN Prospect i ve longitudinal study . SETTING The Dutch province of Zuid-Holl and . PARTICIPANTS At time 1 of data collection , a representative sample of 2076 children aged 4 to 16 years participated in the study . OUTCOME MEASURES Parents rated their children 's ( 4 - 19 years old ) sleep at 5 assessment s by completing the Child Behavior Checklist . Participants reported on their own emotional and behavioral symptoms at a later assessment ( when aged 18 - 32 years ) by completing the Young Adult Self-Report . RESULTS After adjusting for sex , age , socioeconomic status , and parent-rated scores through development for the difficulty being predicted , having any parental reports of sleeping less than others was a risk indicator of high scores on the Anxious/Depressed scale ( odds ratio , 1.43 ; 95 % confidence interval , 1.07 - 1.90 ; P = .01 ) and the Aggressive Behavior scale ( odds ratio , 1.51 ; 95 % confidence interval , 1.13 - 2.02 ; P = .005 ) . There was some ( albeit less robust ) support for links between other reported sleep difficulties and later problems . Parental reports of sleeping more than others and nightmares were not associated with later difficulties . CONCLUSIONS Physicians should inquire about sleep problems during child development and should be aware that some , but perhaps not others , may constitute risk indicators of later difficulties Objective : Sleep problems are common in children with autism spectrum disorders ( ASD ) and ADHD and impact adversely on child and parent well-being . The study evaluated the efficacy of a brief behavioral sleep inter Output:	Changes in cognition and academic skills were not examined in any studies . CONCLUSIONS BSIs improve sleep , at least in the short-term , in children with NNDDs . Benefits may extend to functional improvements in behavior .
MS21209	*TASK* the task is to summarize an input biomedical literature in six sentences *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 chronic myeloid leukaemia ( CML ) with IFN-alpha ( IFN ) is known to confer significant survival benefit , but the drug 's impact on quality of life ( QoL ) in CML is unclear . We describe a cross-sectional comparison of QoL in patients r and omised to long-term treatment with IFN versus no IFN within the UK MRC CML 3 trial , assessing the long-term consequences and psychosocial side effects of IFN therapy . Patients completed the EORTC QoL QLQ-C30 , an in-house leukaemia/IFN question naire , a brief assessment of sexual functioning and demographic details . In total , 163 eligible patients completed question naires ( 85 % response ) . Patients receiving IFN reported significantly worse QoL for emotional , cognitive and social functioning , pain and dyspnoea ( P<0.01 ) , and marginally worse fatigue , nausea and vomiting ( P<0.05 ) . As expected from other IFN use , those on IFN experienced more flu-like and febrile symptoms and skin problems than those not on IFN . In all , 35 % of patients stopped IFN before question naire completion . This made no material difference to the results , except that those continuing on IFN had slightly better self-assessed Global health/QoL than those who had stopped ( P<0.03 ) . IFN treatment adversely affected sexual health after allowing for age and gender . In conclusion , IFN treatment has a significant adverse impact on QoL. Patient awareness of the survival benefits and these QoL effects should enable better-informed decision-making . The impact on QoL of IFN dose , and of imatinib therapy versus IFN in early CP CML , are being investigated . QoL will need evaluating in future studies of combination treatment ( IFN+imatinib ) PURPOSE We conducted a phase III trial to determine whether first-line treatment with raltitrexed , a thymidine synthase inhibitor , and cisplatin results in superior outcome compared with cisplatin alone in patients with malignant pleural mesothelioma ( MPM ) . PATIENTS AND METHODS Eligible patients with histologically proven advanced MPM , not pretreated with chemotherapy , WHO performance status ( PS ) 0 to 2 , and adequate hematological , renal , and hepatic function were r and omly assigned to receive cisplatin 80 mg/m2 IV on day 1 , alone ( arm A ) or combined with raltitrexed 3 mg/m2 ( arm B ) . In patients with measurable disease , response was monitored using the Response Evaluation Criteria in Solid Tumors criteria . Health related quality of life ( HRQOL ) was measured using the European Organisation for Research and Treatment of Cancer QLQ-C30 and Lung Module ( QLQ-LC13 ) . RESULTS Two hundred fifty patients were r and omized : 80 % male ; median age , 58 years ; and WHO PS , 0 , 1 , 2 in 25 , 62 , and 13 % of cases , respectively . There were no toxic deaths . The main grade 3 or 4 toxicities observed were neutropenia and emesis , reported twice as often in the combination arm . Among 213 patients with measurable disease , response rate was 13.6 % ( arm A ) versus 23.6 % ( arm B ; P = .056 ) . No difference in HRQOL was observed on any of the scales . Median overall and 1-year survival in arms A and B were 8.8 ( 95 % CI , 7.8 to 10.8 ) v 11.4 months ( 95 % CI , 10.1 to 15 ) , respectively , and 40 % v 46 % , respectively ( P = .048 ) . CONCLUSION A combination of raltitrexed and cisplatin improves overall survival compared with cisplatin alone . This study confirms that a combination of cisplatin and an antifolate is superior to cisplatin alone in patients with MPM , without harmful effect on HRQOL CONTEXT The Consoli date d St and ards for Reporting of Trials ( CONSORT ) statement was developed to help improve the quality of reports of r and omized controlled trials ( RCTs ) . To date , a paucity of data exists regarding whether it has achieved this goal . OBJECTIVE To determine whether use of the CONSORT statement is associated with improvement in the quality of reports of RCTs . DESIGN AND SETTING Comparative before- and -after evaluation in which reports of RCTs published in 1994 ( pre-CONSORT ) were compared with RCT reports from the same journals published in 1998 ( post-CONSORT ) . We included 211 reports from BMJ , JAMA , and The Lancet ( journals that adopted CONSORT ) as well as The New Engl and Journal of Medicine ( a journal that did not adopt CONSORT and was used as a comparator ) . MAIN OUTCOME MEASURES Number of CONSORT items included in a report , frequency of unclear reporting of allocation concealment , and overall trial quality score based on the Jadad scale , a 5-point quality assessment instrument . RESULTS Compared with 1994 , the number of CONSORT checklist items in reports of RCTs increased in all 4 journals in 1998 , and this increase was statistically significant for the 3 adopter journals ( pre-CONSORT , 23.4 ; mean change , 3.7 ; 95 % confidence interval [ CI ] , 2.1 - 5.3 ) . The frequency of unclear reporting of allocation concealment decreased for each of the 4 journals , and this change was statistically significant for adopters ( pre-CONSORT , 61 % ; mean change , -22 % ; 95 % CI , -38 % to -6 % ) . Similarly , 3 of the 4 journals showed an improvement in the quality score for reports of RCTs , and this increase was statistically significant for adopter journals overall ( pre-CONSORT , 2.7 ; mean change , 0.4 ; 95 % CI , 0.1 - 0.8 ) . CONCLUSION Use of the CONSORT statement is associated with improvements in the quality of reports of RCTs The increasing success of intensive consolidation chemotherapy ( CCT ) as an alternative to bone marrow transplant ( BMT ) in acute myeloid leukaemia ( AML ) necessitates comparison of the impact on quality of life ( QoL ) of these two treatment modalities . Most QoL studies following BMT involve small patient numbers and provide ambivalent results . The present study examines QoL in a large number of patients 1 year from the end of treatment within the United Kingdom Medical Research Council ( UK MRC ) AML10 trial of BMT versus CCT . Allogeneic-BMT ( Allo-BMT ) was observed to have an adverse impact on most QoL dimensions compared with Autologous-BMT ( A-BMT ) and CCT . More patients receiving BMT had mouth dryness problems and worse sexual and social relationships , professional and leisure activities than CCT patients . QoL in A-BMT patients was less impacted than Allo-BMT . Intention-to-treat analysis showed similar results . These results indicate that a reconsideration of treatment strategies is warranted , and that further , good prospect i ve studies are needed to evaluate more clearly the effects of these treatments in long-term survivors The objective of this study was to obtain age- and sex-specific reference values for the European Organization for Research and Treatment of Cancer ( EORTC ) Quality of Life Question naire QLQ-C30 . A r and omly selected sample of the German adult population ( 3015 subjects ) was used , 2081 subjects agreed to take part in the investigation . Most of the scales and symptom items of the question naire proved to be dependent on age and sex . Men reported fewer symptoms than women . Age differences were even more pronounced . Younger people reported better functioning and fewer symptoms . Compared with the results of a similar Norwegian study ( Hjermstad MJ , Fayers PM , Bjordal K , Kaasa S. Health related quality of life in the general Norwegian population assessed by the European Organization for research and treatment of cancer core quality -of-life question naire : The QLQ-C30(+3 ) . J Clin Oncol 1998 , 16 , 1188 - 1196 ) the prevalence of some symptoms was markedly less . Norm values for age and sex groups are given and regression analyses are performed which help to calculate expected mean scores . The results show that age and sex differences must be taken into consideration when different groups of cancer patients are compared . The norm values help to interpret quality of life data for clinicians PURPOSE To date , only a few studies have evaluated the health-related quality of life ( HRQOL ) of patients with chronic lymphocytic leukemia ( CLL ) receiving chemotherapy . Therefore , the German CLL Study Group assessed HRQOL in younger patients with advanced CLL receiving first-line chemotherapy with fludarabine or fludarabine plus cyclophosphamide ( FC ) . PATIENTS AND METHODS Three hundred seventy-five patients younger than 66 years with advanced CLL were r and omly assigned to receive either fludarabine alone ( fludarabine 25 mg/m2/d for 5 days intravenously [ IV ] , repeated every 28 days ) or FC ( fludarabine 30 mg/m2/d for 3 days IV plus cyclophosphamide 250 mg/m2/d for 3 days , repeated every 28 days ) . Six courses of treatment were planned to be administered . The European Organisation for Research and Treatment of Cancer Quality of Life Question naire C30 was sent to all patients at baseline and after 6 , 12 , and 24 months . RESULTS Eighty-nine percent of 362 included patients completed at least one question naire ( 163 fludarabine- and 158 FC-treated patients ) . Comparing the baseline levels of 249 CLL patients with the general German population , significant differences in nearly all HRQOL scales were assessed between the two groups . A multivariate analysis showed no significant differences in all HRQOL scales between both arms . In both treatment arms , symptoms such as fatigue , insomnia , and appetite loss improved to lower levels after the end chemotherapy . Except for lower physical status , no significant difference in HRQOL between male and female patients was evaluated . CONCLUSION Fludarabine-based treatment seems to improve HRQOL little to moderately in younger patients with advanced CLL . No significant difference between fludarabine- and FC-treated patients was observed A cross-sectional study of quality of life ( QOL ) was performed in 98 patients in continued first complete remission ( CR ) for 1–7.4 years , after inclusion in the AML 8A trial which prospect ively compared allogeneic bone marrow transplantation ( AlloBMT ) , autologous BMT ( ABMT ) and intensive consolidation chemotherapy . Several significant differences between the three treatment groups were observed , on the basis of patient self-reports , with regard to somatic symptoms ( mouth sores , cough , hair loss , headache ) , repeated acute medical problems , physical functioning , role functioning , leisure activities and , above all , sexual functioning . There were also significant differences for overall physical condition , and overall quality of life . For all these parameters , the ranking was uniformly AlloBMT lower than ABMT lower than chemotherapy . These differences remain significant after adjustment for time interval between CR and QOL evaluation , sex or age . These results , confirming a higher risk of permanent impairment of QOL after BMT , may have an impact on medical decisions and warrant further studies BACKGROUND Previous work highlighted a number of method ological constraints when reporting health-related quality of life ( HRQOL ) outcomes from r and omized controlled trials ( RCTs ) . Given this , the objective of this study was to investigate whether the quality of such HRQOL reports has improved over time . MATERIAL S AND METHODS On the basis of a predefined set of criteria , 159 RCTs with a HRQOL end point , published between 1990 and 2004 were identified and analyzed . Each study was evaluated by a number of issues ( e.g. sample size and industry sponsorship ) and by the " minimum st and ard checklist for evaluating HRQOL outcomes in cancer clinical trials " . RESULTS The quality of HRQOL reports , as measured by the overall checklist score , was independently related to more recently published studies ( P < 0.0001 ) . This relationship was independent of industry funded , HRQOL end point ( primary versus secondary ) , cancer disease site , size of the study and HRQOL difference between treatment arms . While only 39.3 % of studies published between 1990 and 2000 ( 89/159 RCTs ) were identified as being probably robust , thus likely to support clinical decision making , this percentage was 64.3 % for studies published after 2000 ( 70/159 RCTs ) . CONCLUSION Since we found a significant learning curve in HRQOL trial reporting since 1990 , it can be expected that HRQOL data will increasingly impact on clinical decision making and treatment policies in the near future Federal regulations provide 2 pathways for approval of new agents for the treatment of acute leukemia , regular and accelerated approval . Regular approval requires evidence of clinical benefit , which is generally defined as either prolongation of life or improved quality of life , or an effect on an end point established as a surrogate for clinical benefit . Accelerated approval can be obtained based on demonstration of an effect on a surrogate measure " reasonably likely " to predict clinical benefit , but requires demonstration of clinical benefit after approval as well . The acute leukemias are a heterogeneous and relatively uncommon group of diseases . The design and execution of prospect i ve r and omized clinical trials demonstrating prolongation of life or improved quality of life for patients with these disorders can be difficult and costly and require lengthy follow-up . Thus , the development of novel trial design and inclusion of vali date d surrogate markers for clinical benefit are needed Output:	Imatinib greatly improved HRQOL compared to interferon based treatments in CML patients and fludarabine plus cyclophosphamide does not seem to have a deleterious impact on patient 's HRQOL when compared to fludarabine alone or chlorambucil in CLL patients . This study revealed the paucity of HRQOL research in leukaemia patients . Nonetheless , HRQOL assessment is feasible in RCTs and has the great potential of providing valuable outcomes to further support clinical decision making
MS21210	*TASK* the task is to summarize an input biomedical literature in six sentences *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 conduct of r and omized , controlled trials of nonpharmacologic treatments presents specific challenges that are not adequately addressed in trial reports . OBJECTIVE To develop an extension of the CONSORT ( Consoli date d St and ards of Reporting Trials ) Statement for trials of nonpharmacologic treatments . DESIGN A consensus meeting was organized to develop an extension of the CONSORT Statement that addresses r and omized trials of nonpharmacologic treatments . To prepare for the meeting , a survey was conducted to identify the specific issues for discussion . SETTING Consensus meeting in Paris , France . PARTICIPANTS A total of 33 experts attended the meeting . The experts were method ologists ( n = 17 ) ; surgeons ( n = 6 ) ; editors ( n = 5 ) ; and clinicians involved in rehabilitation ( n = 1 ) , psychotherapy ( n = 2 ) , education ( n = 1 ) , and implantable devices ( n = 1 ) . MEASUREMENTS Experts indicated which of the 22 items on the CONSORT checklist should be modified or which additional items should be added specifically for nonpharmacologic treatments . During a 3-day consensus meeting , all items were discussed and additional method ological issues related to nonpharmacologic research were identified . RESULTS The consensus was that 11 items on the CONSORT checklist needed some modifications for nonpharmacologic trials : item 1 ( title and abstract ) , item 3 ( participants ) , item 4 ( interventions ) , item 7 ( sample size ) , item 8 ( r and omization ) , item 11 ( blinding ) , item 12 ( statistical methods ) , item 13 ( participant flow ) , item 15 ( baseline data ) , item 20 ( discussion : interpretation ) , and item 21 ( generalizability ) . In addition , the meeting participants added 1 item related to implementation of the intervention . LIMITATION Evidence was not always available to support the inclusion of each checklist item . CONCLUSION The methods and processes used to develop this extension could be used for other reporting guidelines . The use of this extension to the CONSORT Statement should improve the quality of reporting r and omized , controlled trials assessing nonpharmacologic treatments PURPOSE Early breast cancer survivors ( BCSs ) report high unmet care needs , and easily accessible care is not routinely available for this growing population . The Breast Cancer E-Health ( BREATH ) trial is a Web-based self-management intervention to support the psychological adjustment of women after primary treatment , by reducing distress and improving empowerment . PATIENTS AND METHODS This multicenter , r and omized , controlled , parallel-group trial evaluated whether care as usual ( CAU ) plus BREATH is superior to CAU alone . BREATH is delivered in sixteen fully automated weekly modules covering early survivorship issues . Two to 4 months post-treatment , BCSs were r and omly assigned to receive CAU + BREATH ( n = 70 ) or CAU alone ( n = 80 ) using a stratified block design ( ratio 1:1 ) . Primary outcomes were distress ( Symptom Checklist-90 ) and empowerment ( Cancer Empowerment Question naire ) , assessed before r and om assignment ( baseline , T0 ) and after 4 ( T1 ) , 6 ( T2 ) , and 10 months ( T3 ) of follow-up . Statistical ( analysis of covariance ) and clinical effects ( reliable change index ) were tested in an intention-to-treat analysis ( T0 to T1 ) . Follow-up effects ( T0 to T3 ) were assessed in assessment completers . RESULTS CAU + BREATH participants reported significantly less distress than CAU-alone participants ( -7.79 ; 95 % CI , -14.31 to -1.27 ; P = .02 ) with a small-to-medium effect size ( d = 0.33 ) , but empowerment was not affected ( -1.71 ; 95 % CI , 5.20 to -1.79 ; P = .34 ) . More CAU + BREATH participants ( 39 of 70 [ 56 % ] ; 95 % CI , 44.1 to 66.8 ) than CAU-alone participants ( 32 of 80 [ 40 % ] ; 95 % CI , 30.0 to 51.0 ) showed clinical ly significant improvement ( P = .03 ) . This clinical effect was most prominent in low-distress BCSs . Secondary outcomes confirmed primary outcomes . There were no between-group differences in primary outcomes during follow-up . CONCLUSION Access to BREATH reduced distress among BCSs , but this effect was not sustained during follow-up Background : Internet-based methods for provision of psychological support and intervention to cancer survivors hold promise for increasing the public impact of such treatments . Purpose : The goal of this controlled pilot study was to examine the effect and potential mechanisms of action of a self-guided , Internet-based coping-skills training group on quality of life outcomes in women with early-stage breast cancer . Methods : Sixty-two women completed baseline evaluations and were r and omized into either a small online coping group or a waiting-list control condition . Results : No main effects for treatment were observed at the 12-week follow up . However , there was a significant interaction between baseline self-reported health status and treatment , such that women with poorer self-perceived health status showed greater improvement in perceived health over time when assigned to the treatment condition . Linguistic analyses revealed that positive changes across quality of life variables were associated with greater expression of negative emotions such as sadness and anxiety , greater cognitive processing , and lower expression of health-related concerns . Conclusions : These results demonstrate the potential efficacy of self-guided Internet coping groups while highlighting the limitations of such groups The aims of this study were to ( a ) identify the predictors of attrition from a fully self-directed intervention , and ( b ) to test whether an intervention to increase gratitude is an effective way to reduce body dissatisfaction . Participants ( N=479 , from the United Kingdom ) aged 18 - 76 years took part in a self-help study via the Internet and were r and omized to receive one of two interventions , gratitude diaries ( n=130 ) , or thought monitoring and restructuring ( n=118 ) or a waitlist control ( n=231 ) for a two week body dissatisfaction intervention . The gratitude intervention ( n=40 ) was as effective as monitoring and restructuring ( n=22 ) in reducing body dissatisfaction , and both interventions were significantly more effective than the control condition ( n=120 ) . Participants in the gratitude group were more than twice as likely to complete the intervention compared to those in the monitoring and restructuring group . Intervention content , baseline expectancy and internal locus of control significantly predicted attrition . This study shows that a gratitude intervention can be as effective as a technique commonly used in cognitive therapy and is superior in retaining participants . Prediction of attrition is possible from both intervention content and psychological variables BACKGROUND The aim of this study was to evaluate the short-term effectiveness of the web-based computer-tailored intervention Kanker Nazorg Wijzer ( Cancer Aftercare Guide ) . The intervention aims to support cancer survivors with managing psychosocial and lifestyle-related issues . In this study , the impact on quality of life , anxiety , depression , and fatigue were evaluated . METHODS Cancer survivors were recruited through 21 Dutch hospitals ( November 2013-June 2014 ) . Outcome measures included quality of life ( European Organization for Research and Treatment of Cancer Quality of Life Question naire-C30 ) , anxiety and depression ( Hospital Anxiety and Depression Scale ) , and fatigue ( Checklist Individual Strength ) . In a r and omized controlled trial with an intervention group ( n = 231 ) and a waiting list control group ( n = 231 ) , the short-term effectiveness was evaluated through multilevel linear regression analyses , controlling for selective dropout , baseline differences , and several demographic and disease-related characteristics . RESULTS In total , 188 participants of the intervention group and 221 of the control group completed the 6-month measurement ( dropout = 11.5 % ) . The intervention was effective in reducing depression ( B = -0.63 , p = 0.007 , f2 = 0.019 , d = 0.21 ) and fatigue ( B = -4.36 , p = 0.020 , f2 = 0.013 , d = 0.21 ) . In addition , effects were found for emotional ( B = 3.47 , p = 0.022 , f2 = 0.013 , d = 0.15 ) and social functioning ( B = 3.95 , p = 0.011 , f2 = 0.017 , d = 0.15 ) , although this evidence was less strong . There were indications that the effects of fatigue and social functioning were influenced by module use . CONCLUSIONS While effect sizes were small , they can be considered as clinical ly relevant . With the Cancer Aftercare Guide being an effective , low-intensive , and easy accessible intervention , it could serve as a first step in stepped care for needs assessment and initial support for psychosocial problems that are present after cancer treatment . Copyright © 2016 John Wiley & Sons , Addressing psychosocial and quality of life needs is central to provision of excellent care for people with advanced cancer . This study tested a brief nurse-delivered intervention to address the needs of urban women with advanced breast cancer . This study was conducted at four large urban hospitals in Australia . One hundred and five women with advanced breast cancer were recruited and r and omised to receive the intervention or usual care , then asked to complete the European Organisation of Research and Treatment of Quality of life Q-C30 version ( 2.0 ) ( EORTC Q-C30 ) ( version 2 ) and Supportive Care Needs Survey ( SCNS ) at 1 month and 3 months postrecruitment . No significant differences were detected between intervention and usual care groups in the SCNS or the EORTC Q-C30 subscale scores . However , when the groups were divided into high needs ( score of above 50 ) and low baseline needs ( score of 50 or below ) for each SCNS subscale , a significant difference between intervention and usual care groups was found in the psychological/emotional subscale among women with high baseline needs . In conclusions , this study demonstrated that a face-to-face session and follow-up phone call with a breast care nurse significantly reduced the psychological and emotional needs of those with high initial needs . There was no evidence of the intervention influencing the quality of life ; or perceived needs of women with low initial psychological/emotional needs or perceived needs in other domains . Possibly , the intervention was not sufficiently intense to achieve an effect BACKGROUND Prostate cancer ( PCa ) poses many emotional and physical challenges for men following treatment . The unmet support needs of these men are well documented , and access to psychosocial support remains problematic . OBJECTIVES To assess the efficacy of an online psychological intervention for men who have localised PCa . DESIGN , SETTING , AND PARTICIPANTS We undertook a r and omised controlled trial to evaluate the intervention . Participants were r and omly allocated to one of three conditions : My Road Ahead ( MRA ) alone ( MRA Only ) , MRA plus access to an online forum ( MRA+Forum ) , and access to the forum alone ( Forum ) . INTERVENTION The intervention was a 10-week self-guided online psychological intervention called My Road Ahead that consisted of six themed modules design ed to facilitate improved emotional well-being in the context of PCa as well as a moderated peer forum . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Pre- and postintervention assessment s of psychological distress ( the 21- question Depression , Anxiety and Stress Scale ) [ 1 ] and the Prostate Cancer-related Quality of Life scale [ 2 ] were conducted . Multivariate analysis of variance , regression , and structural equation modelling were used to analyse the data . RESULTS AND LIMITATIONS In total , 142 participants were r and omly allocated to one of the three intervention arms . The mean age of participants was 61 yr of age ( st and ard deviation : 7 ) , and 88 % had undergone radical prostatectomy . A significant improvement in psychological distress was observed for participants who had access to the combined condition ( MRA+Forum ) with a moderate effect size ( p=0.02 ; partial η(2)=0.07 ) . In particular , the decline in the mean level of psychological distress was 8.8 units larger for the MRA+Forum group than the Forum group ( 95 % confidence interval [ CI ] , 0.9 - 16.7 ) . Although the decline in the mean level of psychological distress was 7.0 units larger for the MRA+Forum group than for the MRA Only group , this difference was not significant ( 95 % CI , 1.1 - 15.1 ) . Structural equation modelling indicated that reductions in health worry and regret contributed significantly to the reductions in psychological distress for the MRA+Forum condition . CONCLUSIONS This study is the first , to our knowledge , that has evaluated a self-guided online psychological intervention tailored to the specific needs of men who have PCa . The findings of this study indicate the potential for this programme to deliver support that men may not otherwise receive . PATIENT SUMMARY This study found that men who have localised prostate cancer who received access to the online psychological intervention called My Road Ahead combined with the online peer discussion forum had significantly improved reductions in distress compared with those who received access to the online intervention alone or the forum alone PURPOSE A first breast cancer recurrence creates considerable distress , yet few psychosocial interventions directed at this population have been reported . The Southwest Oncology Group conducted a phase III r and omized trial to evaluate the effectiveness of a brief telephone intervention . PATIENTS AND METHODS Three hundred five women experiencing a first Output:	No evidence of survival benefit was found . Group programs had the strongest evidence -base for efficacy ; individual and low-intensity therapy had insufficient evidence to form conclusions . Group interventions had longest intervention duration s and lowest uptake and adherence ; low-intensity interventions had shortest duration s and highest uptake and adherence . Disparities in uptake , adherence , and reach were evident , with the demographic profile of participants polarised to young , Caucasian , English-speaking , partnered women . CONCLUSIONS There remains a paucity of psychological interventions for women with metastatic breast cancer . Those that exist have an inconsistent evidence -base across the range of patient-reported outcomes .
MS21211	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background To determine the effectiveness of three different local injection modalities in the treatment of lateral epicondilitis . Methods In a prospect i ve r and omized study on lateral epicondilitis , 75 patients were divided into three equal groups A , B and C ( n = 25 ) and were treated using three different method of local injection . The patients in group A were treated with local injection of a steroid ( 1 mL triamcinolone ) combined with local anaesthetic ( 1 mL lidocaine ) , those in group B were treated with injection of local anaesthetic ( 1 mL lidocaine ) combined with peppering technique and those in group C with local injection of a steroid ( 1 mL triamcinolone ) combined with local anaesthetic ( 1 mL lidocaine ) and peppering technique . The outcome was defined by measuring the elbow pain during the activity using a 10-cm visual analogue scale ( VAS ) and satisfaction with the treatment using a scoring system based on the criteria of the Verhaar et al. at 3 weeks and 6 months after the injection and compared with the pre-treatment condition . Results There were significant ( P = 0.006 ) differences in the successful outcomes between the three groups at 6 months . In group C in which local steroid + peppering injection technique were used ; excellent results were obtained in 84 % of patients comparing to 36 % and 48 % for patients in groups A and B , respectively . The successful outcomes were statistically higher in group C comparing to group A ( P = 0.002 ) and group B ( P = 0.011 ) . In all groups , there was a significantly lower pain ( VAS ) at the 3-week and 6-month follow-ups comparing to the pre-treatment condition . VAS measured at 6-month follow-up were significantly lower in group C comparing to other groups ( P = 0.002 ) . Conclusion In the treatment of lateral epicondilitis , combination of corticosteroid injections with peppering is more effective than corticosteroid injections or peppering injections alone and produces better clinical results Background The aim of this prospect i ve r and omized clinical trial was to investigate the efficacy of a home-based program of isometric strengthening exercises for the treatment of the lateral epicondylitis ( LE ) of the distal humerus . We hypothesized that 1 ) use of isometric strengthening exercises would result in clinical benefits similar to those provided by medication and pain relief and 2 ) functional improvements after exercise would be time-dependent . Methods Patients were assigned to one of two groups : 1 ) an immediate physical therapy group ( group I ) , or 2 ) a delayed physical therapy group ( group D ) . Group I patients ( n = 16 ) were instructed how to do the exercises at their first clinic visit and immediately carried out the exercise program . Group D patients ( n = 15 ) learned and did the exercises after being on medications for 4 weeks . Results Outcomes at the 1-month clinic visit indicated that pain ( measured using a visual analogue scale [ VAS ] ) had been significantly reduced in group I compared to group D ( p < 0.01 ) . However , significant differences between groups were not found at 3- , 6- , and 12-month follow-up for either VAS scores or Mayo elbow performance scores . For modified Nirschl/Pettrone scores , a significant difference between groups was found only at the 1-month follow-up visit . By then , the number of participants who returned to all activities with no pain or occasional mild pain was six ( 37 % ) in Group I and two ( 13 % ) in Group D ( p = 0.031 ) . At the final follow-up visit , 88 % of all participants performed physical activities without pain . Conclusions Isometric strengthening exercises done early in the course of LE ( within 4 weeks ) provides a clinical ly significant improvement & NA ; Forty‐nine patients suffering from lateral humeral epicondylalgia were enrolled in a double‐blind study to observe the effects of Ga‐As laser applied to acupuncture points . The Mid 1500 IRRADIA laser machine was used , wavelength : 904 nm , mean power output : 12 mW , peak value : 8.3 W ; frequency : 70 Hz ( pulse train ) . Localization of points : LI 10 , 11 , 12 , Lu 5 and SJ 5 . Each point was treated for 30 sec result ing in a dose of treatment of 0.36 J/point . The patients were treated 2–3 times weekly with 10 treatments in all . Follow‐ups were done after 3 months and 1 year . No significant differences were observed between the laser and the placebo group in relation to the subjective or objective outcome after 10 treatments or at the follow‐ups Kazemi M , Azma K , Tavana B , Rezaiee Moghaddam F , Panahi A : Autologous blood versus corticosteroid local injection in the short-term treatment of lateral elbow tendinopathy : A r and omized clinical trial of efficacy . Objective : To compare local corticosteroid with autologous blood injections for the short-term treatment of lateral elbow tendinopathy . Design : A single blind , r and omized clinical trial was performed in an outpatient clinic at a university hospital . Sixty patients aged 27–64 yrs with a new episode of tennis elbow were recruited . Thirty patients were r and omized to methylprednisolone and 30 to autologous blood group over 1 yr . Severity of pain within last 24 hrs ; limb function ; pain and strength in maximum grip ; disabilities of the arm , shoulder , and h and quick question naire ( Quick DASH ) scores ; modified Nirschl scores ; and pressure pain threshold were evaluated before injection and at 4 and 8 wks after injection . We analyzed our data with the & khgr;2 and t test . Results : Within-group analyses showed better results for autologous blood ( all P values < 0.001 except for grip strength , P = 0.005 ) . In the corticosteroid group , differences in severity of pain ( P = 0.008 ) and grip strength ( P = 0.001 ) were significant . At 4 wks , between-group analyses showed superiority of autologous blood for severity of pain ( P = 0.001 ) , pain in grip ( P = 0.002 ) , pressure pain threshold ( P = 0.031 ) , and Quick DASH question naire score ( P = 0.004 ) . There were no significant differences in modified Nirschl score , grip strength , and limb function . At 8 wks , autologous blood was more effective in all the outcomes ( all P values < 0.001 ) . Conclusions : Autologous blood was more effective in short term than the corticosteroid injection Background There is conflicting evidence regarding extracorporeal shock wave treatment for chronic tennis elbow . Hypothesis Treatment with repetitive low-energy extracorporeal shock wave treatment is superior to repetitive placebo extracorporeal shock wave treatment . Methods Seventy-eight patients enrolled in a placebo-controlled trial . All patients were tennis players with recalcitrant MRIconfirmed tennis elbow of at least 12 months ’ duration . Patients were r and omly assigned to receive either active low-energy extracorporeal shock wave treatment given weekly for 3 weeks ( treatment group 1 ) or an identical placebo extracorporeal shock wave treatment ( sham group 2 ) . Main outcome measure was pain during resisted wrist extension at 3 months ; secondary measures were > 50 % reduction of pain and the Upper Extremity Function Scale . Results At 3 months , there was a significantly higher improvement in pain during resisted wrist extension in group 1 than in group 2 ( mean [ SD ] improvement , 3.5 [ 2.0 ] and 2.0 [ 1.9 ] ; P= .001 for between-group difference of improvement ) and in the Upper Extremity Function Scale ( mean [ SD ] improvement , 23.4 [ 14.8 ] and 10.9 [ 14.9 ] ; P < .001 for between-group difference of improvement ) . In the treatment group , 65 % of patients achieved at least a 50 % reduction of pain , compared with 28 % of patients in the sham group ( P= .001 for between-group difference ) . Conclusion Low-energy extracorporeal shock wave treatment as applied is superior to sham treatment for tennis elbow Abstract Objective To investigate the efficacy of physiotherapy compared with a wait and see approach or corticosteroid injections over 52 weeks in tennis elbow . Design Single blind r and omised controlled trial . Setting Community setting , Brisbane , Australia . Participants 198 participants aged 18 to 65 years with a clinical diagnosis of tennis elbow of a minimum six weeks ' duration , who had not received any other active treatment by a health practitioner in the previous six months . Interventions Eight sessions of physiotherapy ; corticosteroid injections ; or wait and see . Main outcome measures Global improvement , grip force , and assessor 's rating of severity measured at baseline , six weeks , and 52 weeks . Results Corticosteroid injection showed significantly better effects at six weeks but with high recurrence rates thereafter ( 47/65 of successes subsequently regressed ) and significantly poorer outcomes in the long term compared with physiotherapy . Physiotherapy was superior to wait and see in the short term ; no difference was seen at 52 weeks , when most participants in both groups reported a successful outcome . Participants who had physiotherapy sought less additional treatment , such as non-steroidal anti-inflammatory drugs , than did participants who had wait and see or injections . Conclusion Physiotherapy combining elbow manipulation and exercise has a superior benefit to wait and see in the first six weeks and to corticosteroid injections after six weeks , providing a reasonable alternative to injections in the mid to long term . The significant short term benefits of corticosteroid injection are paradoxically reversed after six weeks , with high recurrence rates , implying that this treatment should be used with caution in the management of tennis elbow OBJECTIVE The aim of this study was to evaluate the effectiveness of 904-nm low-level laser therapy ( LLLT ) in the management of lateral epicondylitis . BACKGROUND DATA Lateral epicondylitis is characterized by pain and tenderness over the lateral elbow , which may also result in reduction in grip strength and impairment in physical function . LLLT has been shown effective in its therapeutic effects in tissue healing and pain control . METHODS Thirty-nine patients with lateral epicondylitis were r and omly assigned to receive either active laser with an energy dose of 0.275 J per tender point ( laser group ) or sham irradiation ( placebo group ) for a total of nine sessions . The outcome measures were mechanical pain threshold , maximum grip strength , level of pain at maximum grip strength as measured by the Visual Analogue Scale ( VAS ) and the subjective rating of physical function with Disabilities of the Arm , Shoulder and H and ( DASH ) question naire . RESULTS Significantly greater improvements were shown in all outcome measures with the laser group than with the placebo group ( p < 0.0125 ) , except in the two subsections of DASH . CONCLUSION This study revealed that LLLT in addition to exercise is effective in relieving pain , and in improving the grip strength and subjective rating of physical function of patients with lateral epicondylitis Background : Chronic lateral elbow epicondylitis is a tendinosis with angiofibrolastic degeneration of the wrist extensors ’ origin . Healing of this lesion is reported with the use of autologous blood as well as with platelet-rich plasma ( PRP ) . Purpose : A comparative study of these 2 treatments was conducted in an effort to investigate the possible advantages of PRP . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : Twenty-eight patients were divided equally into 2 groups , after blocked r and omization . Group A was treated with a single injection of 3 mL of autologous blood and group B with 3 mL of PRP under ultrasound guidance . A st and ardized program of eccentric muscle strengthening was followed by all patients in both groups . Evaluation using a pain visual analog scale ( VAS ) and Liverpool elbow score was performed at 6 weeks , 3 months , and 6 months . Results : The VAS score improvement was larger in group B at every follow-up interval but the difference was statistically significant only at 6 weeks , when mean improvement was 3.8 points ( 95 % confidence interval [ CI ] , 3.1 - 4.5 ) in group B ( 61.47 % improvement ) and 2.5 points ( 95 % CI , 1.9 - 3.1 ) in group A ( 41.6 % improvement ) ( P < .05 ) . No statistically significant difference was noted between groups regarding Liverpool elbow score . Conclusion : Regarding pain reduction , PRP treatment seems to be an effective treatment for chronic lateral elbow epicondylitis and superior to autologous blood in the short term . Defining details of indications , best PRP concentration , number and time of injections , as well as rehabilitation protocol might increase the method ’s effectiveness . Additionally , the possibility of cost reduction of the method might justify the use of PRP over autologous whole blood for chronic or refractory tennis elbow Abstract Background . Chronic tennis elbow ( lateral epicondylosis ) is a common disorder . Like other chronic soft-tissue pain conditions it is often difficult to treat successfully . The effects of exercise have been discussed , but no convincing evidence has been put forward so far , and a simple protocol for exercise is lacking . Aims of the study . This study is a r and omized , controlled , clinical trial of the effect of exercise versus expectation ( wait-list ) on pain , muscle strength , function , and quality of life in patients with long-st and ing lateral epicondylosis . Methods . Eighty-one subjects with tennis elbow lasting for more than 3 months were r and omly allocated to an exercise group ( n = 40 ) or a reference group ( n Output:	There may be a short-term pain relief advantage found with the application of corticosteroids , but no demonstrable long-term pain relief . Injection of botulinum toxin A and prolotherapy are superior to placebo but not to corticosteroids , and botulinum toxin A is likely to produce concomitant extensor weakness . Platelet-rich plasma or autologous blood injections have been found to be both more and less effective than corticosteroid injections . Non-invasive treatment methods such as bracing , physical therapy , and extracorporeal shockwave therapy do not appear to provide definitive benefit regarding pain relief . Some studies of low-level laser therapy show superiority to placebo whereas others do not . Conclusions There are multiple r and omized controlled trials for non-surgical management of lateral epicondylitis , but the existing literature does not provide conclusive evidence that there is one preferred method of non-surgical treatment for this condition .
MS21212	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: UNLABELLED PSA-driven screening has been applied to a large part of the male population in many countries . An elevated PSA in secondary screens may indicate benign enlargement of the prostate rather than prostate cancer . In such cases the yearly rate of increase of PSA ( PSA velocity [ PSAV ] ) may improve the test characteristics of PSA . MATERIAL S AND METHODS Data from the European R and omized Study of Screening for Prostate Cancer Rotterdam are used to study the issue . Relative sensitivity , relative specificity , and positive predictive value ( PPV ) are calculated . Logistic regression analysis is used to compare odds ratios for positive biopsies . The relationship between PSAV and parameters of tumour aggressiveness is investigated . RESULTS Five hundred eighty-eight consecutive participants were identified who presented at their first screening with PSA values < 4.0 and who progressed to PSA values > 4.0 ng/ml four years later . None were biopsied in round one , all were biopsied in round two . Relative sensitivity and specificity depend strongly on PSAV cut-offs of 0.25 - 1.0 ng/ml/yr . The use of PSAV cut-offs does not improve the PPV of the PSA cut-off of 4.0 ng/ml , nor do any of the PSAV cut-offs improve the odds ratio for identifying prostate cancer with respect to the cut-off value of 4.0 ng/ml . The rate of aggressive cancers seems to increase with increasing PSAV . CONCLUSIONS PSAV does not improve the detection characteristics of a PSA cut-off of 4.0 ng/ml in secondary screening after four years BACKGROUND Several trials evaluating the effect of prostate-specific antigen ( PSA ) testing on prostate-cancer mortality have shown conflicting results . We up date d prostate-cancer mortality in the European R and omized Study of Screening for Prostate Cancer with 2 additional years of follow-up . METHODS The study involved 182,160 men between the ages of 50 and 74 years at entry , with a predefined core age group of 162,388 men 55 to 69 years of age . The trial was conducted in eight European countries . Men who were r and omly assigned to the screening group were offered PSA-based screening , whereas those in the control group were not offered such screening . The primary outcome was mortality from prostate cancer . RESULTS After a median follow-up of 11 years in the core age group , the relative reduction in the risk of death from prostate cancer in the screening group was 21 % ( rate ratio , 0.79 ; 95 % confidence interval [ CI ] , 0.68 to 0.91 ; P=0.001 ) , and 29 % after adjustment for noncompliance . The absolute reduction in mortality in the screening group was 0.10 deaths per 1000 person-years or 1.07 deaths per 1000 men who underwent r and omization . The rate ratio for death from prostate cancer during follow-up years 10 and 11 was 0.62 ( 95 % CI , 0.45 to 0.85 ; P=0.003 ) . To prevent one death from prostate cancer at 11 years of follow-up , 1055 men would need to be invited for screening and 37 cancers would need to be detected . There was no significant between-group difference in all-cause mortality . CONCLUSIONS Analyses after 2 additional years of follow-up consoli date d our previous finding that PSA-based screening significantly reduced mortality from prostate cancer but did not affect all-cause mortality . ( Current Controlled Trials number , IS RCT N49127736 . ) BACKGROUND The optimal upper limit of the normal range for prostate-specific antigen ( PSA ) is unknown . We investigated the prevalence of prostate cancer among men in the Prostate Cancer Prevention Trial who had a PSA level of 4.0 ng per milliliter or less . METHODS Of 18,882 men enrolled in the prevention trial , 9459 were r and omly assigned to receive placebo and had an annual measurement of PSA and a digital rectal examination . Among these 9459 men , 2950 men never had a PSA level of more than 4.0 ng per milliliter or an abnormal digital rectal examination , had a final PSA determination , and underwent a prostate biopsy after being in the study for seven years . RESULTS Among the 2950 men ( age range , 62 to 91 years ) , prostate cancer was diagnosed in 449 ( 15.2 percent ) ; 67 of these 449 cancers ( 14.9 percent ) had a Gleason score of 7 or higher . The prevalence of prostate cancer was 6.6 percent among men with a PSA level of up to 0.5 ng per milliliter , 10.1 percent among those with values of 0.6 to 1.0 ng per milliliter , 17.0 percent among those with values of 1.1 to 2.0 ng per milliliter , 23.9 percent among those with values of 2.1 to 3.0 ng per milliliter , and 26.9 percent among those with values of 3.1 to 4.0 ng per milliliter . The prevalence of high- grade cancers increased from 12.5 percent of cancers associated with a PSA level of 0.5 ng per milliliter or less to 25.0 percent of cancers associated with a PSA level of 3.1 to 4.0 ng per milliliter . CONCLUSIONS Biopsy-detected prostate cancer , including high- grade cancers , is not rare among men with PSA levels of 4.0 ng per milliliter or less -- levels generally thought to be in the normal range PURPOSE Prostate specific antigen is a glycoprotein found almost exclusively in normal and neoplastic prostate cells . Prostate specific antigen doubling time , or the change in prostate specific antigen over time , has emerged as a useful predictive marker for assessing disease outcome in patients with prostate cancer . It is important to agree on definitions and values for the calculation of prostate specific antigen doubling time , and to develop a common approach to outcome analysis and reporting . MATERIAL S AND METHODS In September 2006 a conference was held at the National Cancer Institute in Bethesda , Maryl and to define these parameters and develop guidelines for their use . RESULTS The Prostate Specific Antigen Working Group defined criteria regarding prostate specific antigen doubling time including the calculation of prostate specific antigen doubling time , evidence to support prostate specific antigen doubling time as a predictive factor in the setting of biochemical recurrence and the use of prostate specific antigen doubling time as a stratification factor in clinical trials . CONCLUSIONS We propose that investigators calculate prostate specific antigen doubling time before enrolling patients in clinical studies and calculate it as an additional measurement of therapeutic activity . We believe we have developed practical guidelines for the calculation of prostate specific antigen doubling time and its use as a measurement of prognosis and outcome . Furthermore , the use of common st and ards for prostate specific antigen doubling time in clinical trials is important as we determine which treatments should progress to r and omized trials in which " hard " end points such as survival will be used Prostate-specific antigen velocity ( PSAV ) is one of the oldest concepts in PSA screening , yet today it is one of the most controversial . Publication of a wide range of studies with different design s , study population s , and results has fueled uncertainty about the best way to use PSAV and confused the issue of its utility in the early detection setting . Studies of disease prognosis suggest that PSAV is strongly associated with lethal cancers . However , prospect i ve screening trials find that PSAV is at best a weak predictor of high-risk disease . In this commentary , we synthesize and reconcile the evidence about the value of PSAV in the early detection setting . We review recent studies of PSAV and determine a set of statistical considerations that we believe to be critical in study evaluation and interpretation . We explain why the association between PSAV and disease-specific survival does not necessarily imply that PSAV will be a useful screening tool . In addition , we argue that the st and ard concept of PSAV -- the absolute change in PSA per year -- confuses disease aggressiveness with the interval from disease onset to detection . We therefore recommend that other methods be explored to incorporate information about PSA kinetics that could ultimately improve-- and even transform -- how we detect and treat prostate cancer BACKGROUND Screening for prostate cancer advances the time of diagnosis ( lead time ) and detects cancers that would not have been diagnosed in the absence of screening ( overdetection ) . Both consequences have considerable impact on the net benefits of screening . METHODS We developed simulation models based on results of the Rotterdam section of the European R and omized Study of Screening for Prostate Cancer ( ERSPC ) , which enrolled 42,376 men and in which 1498 cases of prostate cancer were identified , and on baseline prostate cancer incidence and stage distribution data . The models were used to predict mean lead times , overdetection rates , and ranges ( corresponding to approximate 95 % confidence intervals ) associated with different screening programs . RESULTS Mean lead times and rates of overdetection depended on a man 's age at screening . For a single screening test at age 55 , the estimated mean lead time was 12.3 years ( range = 11.6 - 14.1 years ) and the overdetection rate was 27 % ( range = 24%-37 % ) ; at age 75 , the estimates were 6.0 years ( range = 5.8 - 6.3 years ) and 56 % ( range = 53%-61 % ) , respectively . For a screening program with a 4-year screening interval from age 55 to 67 , the estimated mean lead time was 11.2 years ( range = 10.8 - 12.1 years ) , and the overdetection rate was 48 % ( range = 44%-55 % ) . This screening program raised the lifetime risk of a prostate cancer diagnosis from 6.4 % to 10.6 % , a relative increase of 65 % ( range = 56%-87 % ) . In annual screening from age 55 to 67 , the estimated overdetection rate was 50 % ( range = 46%-57 % ) and the lifetime prostate cancer risk was increased by 80 % ( range = 69%-116 % ) . Extending annual or quadrennial screening to the age of 75 would result in at least two cases of overdetection for every clinical ly relevant cancer detected . CONCLUSIONS These model-based lead-time estimates support a prostate cancer screening interval of more than 1 year BACKGROUND The prostate component of the Prostate , Lung , Colorectal , and Ovarian ( PLCO ) Cancer Screening Trial was undertaken to determine whether there is a reduction in prostate cancer mortality from screening using serum prostate-specific antigen ( PSA ) testing and digital rectal examination ( DRE ) . Mortality after 7 - 10 years of follow-up has been reported previously . We report extended follow-up to 13 years after the trial . METHODS A total of 76 685 men , aged 55 - 74 years , were enrolled at 10 screening centers between November 1993 and July 2001 and r and omly assigned to the intervention ( organized screening of annual PSA testing for 6 years and annual DRE for 4 years ; 38 340 men ) and control ( usual care , which sometimes included opportunistic screening ; 38 345 men ) arms . Screening was completed in October 2006 . All incident prostate cancers and deaths from prostate cancer through 13 years of follow-up or through December 31 , 2009 , were ascertained . Relative risks ( RRs ) were estimated as the ratio of observed rates in the intervention and control arms , and 95 % confidence intervals ( CIs ) were calculated assuming a Poisson distribution for the number of events . Poisson regression modeling was used to examine the interactions with respect to prostate cancer mortality between trial arm and age , comorbidity status , and pretrial PSA testing . All statistical tests were two-sided . RESULTS Approximately 92 % of the study participants were followed to 10 years and 57 % to 13 years . At 13 years , 4250 participants had been diagnosed with prostate cancer in the intervention arm compared with 3815 in the control arm . Cumulative incidence rates for prostate cancer in the intervention and control arms were 108.4 and 97.1 per 10 000 person-years , respectively , result ing in a relative increase of 12 % in the intervention arm ( RR = 1.12 , 95 % CI = 1.07 to 1.17 ) . After 13 years of follow-up , the cumulative mortality rates from prostate cancer in the intervention and control arms were 3.7 and 3.4 deaths per 10 000 person-years , respectively , result ing in a non-statistically significant difference between the two arms ( RR = 1.09 , 95 % CI = 0.87 to 1.36 ) . No statistically significant interactions with respect to prostate cancer mortality were observed between trial arm and age ( P(interaction ) = .81 ) , pretrial PSA testing ( P(interaction ) = .52 ) , and comorbidity ( P(interaction ) = .68 ) . CONCLUSIONS After 13 years of follow-up , there was no evidence of a mortality benefit for organized annual screening in the PLCO trial compared with opportunistic screening , which forms part of usual care , and there was no apparent interaction with age , baseline comorbidity , or pretrial PSA testing PURPOSE Preoperative prostate-specific antigen ( PSA ) velocity ( PSAV ) , or the rate of PSA rise before diagnosis , predicts for risk of cancer death after Output:	The preponderance of evidence suggests that there is high collinearity between PSA and PSAV and therefore the calculation of PSAV adds little to the measurement of PSA level . PSAV calculation has been advocated by many investigators as a strategy to improve the screening and clinical management of patients with CaP. However , when PSAV definitions are rigorously applied , its calculation does not significantly enhance the clinical performance of PSA alone
MS21213	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE : The objective of this study was to identify the risk factors for delays in chemotherapy after rectal cancer surgery and evaluate the effects of delayed therapy on long-term outcomes . We also sought to clarify what time frame should be used to define delayed adjuvant chemotherapy . BACKGROUND : Postoperative complications have been found to influence the timing of chemotherapy in patients with colon cancer . Delays in chemotherapy have been shown to be associated with worse overall and disease-free survival in patients with colorectal cancer , although the timing of delay has not been agreed upon in the literature . STUDY DESIGN : We performed a retrospective review of a prospect ively maintained rectal cancer data base . Univariate analysis was used to identify risk factors for delayed chemotherapy . Kaplan-Meier curves were generated to compare overall and disease-free survival in patients based on complications and timing of chemotherapy . SETTING S : This study was performed at the University of Wisconsin Hospital , Madison , Wisconsin , between 1995 and 2012 . PATIENTS : Patients with rectal cancer who underwent proctectomy with curative intent were included in this study . OUTCOME MEASURES : Timing of chemotherapy , 30-day complications , and 30-day readmissions were the main outcome measures . RESULTS : Postoperative complications and 30-day readmissions were associated with delays in chemotherapy ≥8 weeks after surgery . Patients who received chemotherapy ≥8 weeks postoperatively were found to have worse local and distant recurrence rates and worse overall survival in comparison with patients who received chemotherapy within 8 weeks of surgery . LIMITATIONS : The limitations of this study include its retrospective nature and that it was performed at a single institution . CONCLUSIONS : We found complications and readmissions to be risk factors for delayed chemotherapy . Patients who received therapy ≥8 weeks postoperatively had worse disease-free and overall survival BACKGROUND Whether adjuvant chemotherapy improves survival of patients with non-small-cell lung cancer ( NSCLC ) is not known . We aim ed to compare the effect of adjuvant vinorelbine plus cisplatin versus observation on survival in patients with completely resected NSCLC . METHODS 840 patients with stage IB-IIIA NSCLC from 101 centres in 14 countries were r and omly assigned to observation ( n=433 ) or to 30 mg/m(2 ) vinorelbine plus 100 mg/m(2 ) cisplatin ( n=407 ) . Postoperative radiotherapy was not m and atory and was undertaken according to every centre 's policy . The primary endpoint was overall survival . Analysis was by intention to treat . This trial is registered as an International St and ard R and omised Controlled Trial , number IS RCT N95053737 . FINDINGS 367 patients in the chemotherapy group and 431 in the control group received their assigned treatment . 301 ( 36 % ) patients had stage IB disease , 203 ( 24 % ) had stage II disease , and 325 ( 39 % ) had stage IIIA disease . Tolerance to chemotherapy mainly included neutropenia in 335 ( 92 % ) patients and febrile neutropenia in 34 ( 9 % ) ; seven ( 2 % ) toxic deaths were also recorded . Compliance was greater with cisplatin than with vinorelbine ( median dose intensity 89 % [ range 17 - 108 ] vs 59 % [ 17 - 100 ] ) . After a median follow-up of 76 months ( range 43 - 116 ) , median survival was 65.7 months ( 95 % CI 47.9 - 88.5 ) in the chemotherapy group and 43.7 ( 35.7 - 52.3 ) months in the observation group . Adjusted risk for death was significantly reduced in patients assigned chemotherapy compared with controls ( hazard ratio 0.80 [ 95 % CI 0.66 - 0.96 ] ; p=0.017 ) . Overall survival at 5 years with chemotherapy improved by 8.6 % , which was maintained at 7 years ( 8.4 % ) . INTERPRETATION Adjuvant vinorelbine plus cisplatin extends survival in patients with completely resected NSCLC , better defining indication of adjuvant chemotherapy We report a single-centre prospect i ve audit of 29 lung cancer patients who were awaiting radical ( potentially curative ) radiotherapy . This was the total number assessed as suitable for radical treatment by one consultant during 1999 . At the time of assessment they had been newly diagnosed and staged with a computed tomographic ( CT ) scan of chest . They had a subsequent CT scan prior to starting treatment for the purpose of planning the radiation fields . We have now measured tumour size on the diagnostic scans and compared this with the size on the planning scans . We have documented the delay between diagnostic and planning CT scanning and the total time between first hospital visit and starting treatment . Two patients had progression of symptoms while on the waiting list , making them unfit for radical treatment , and another four had tumour progression on planning CT such that the tumour volume was too large for radical treatment . Therefore , 21 % of potentially curable patients became incurable on the waiting list . The delay between diagnostic and planning CT scans ranged from 18 to 131 days ( median 54 ) , with increases in the cross-sectional tumour size over that period ranging zero to 373 % . The delay between the first hospital visit and starting treatment was 35 - 187 days ( median 94 ) ; between the date of the radiotherapy request and the starting date for treatment it was 23 - 61 days ( median 44 ) . Limited access to specialists is the reason most often advanced for the poor performance of the UK in treating lung cancer . This study demonstrates that , even for the select minority of patients who have specialist referral and are deemed suitable for potentially curative treatment , the outcome is prejudiced by waiting times that allow tumour progression The purpose of this study was to examine the effect on survival of delaying the start of adjuvant chemotherapy for early breast cancer for up to 3 months after surgery . In the nation-wide clinical trials of the Danish Breast Cancer Cooperative Group , 7501 breast cancer patients received chemotherapy within 3 months of surgery between 1977 and 1999 : 352 with classical cyclofosfamide , metotrexate and 5-fluorouracil ( CMF ) ; 6065 with CMF i.v . and 1084 with cyclofosfamide , epirubicin and 5-fluorouracil . For the analysis , the time between surgery and the start of chemotherapy was divided into four strata ( 1–3 , 4 , 5 and 6–13 weeks ) . The results show that within the three groups of chemotherapy , there was an even distribution of known prognostic factors across the four strata of initiation of chemotherapy . There was no pattern indicating a benefit from early start of chemotherapy . No significant interactions were found for subgroups of patients with a poorer prognosis ( many involved lymph nodes , high- grade malignancies or hormone receptor negative disease ) . In conclusion , we have found no evidence for a survival benefit due to early initiation of adjuvant chemotherapy within the first 2–3 months after surgery PURPOSE Theoretically , patients with early breast cancer might benefit from starting adjuvant chemotherapy soon after surgery , and this would have important clinical implication s. We have addressed this question from a large , single-center data base in which the majority of patients received anthracyclines . PATIENTS AND METHODS A total of 1161 patients from a prospect ively maintained data base treated with adjuvant chemotherapy for early breast cancer at the Royal Marsden Hospital ( London , United Kingdom ) , including 686 ( 59 % ) receiving anthracyclines , were retrospectively analyzed . The disease-free survival ( DFS ) and overall survival ( OS ) of the 368 patients starting chemotherapy within 21 days of surgery ( group A ) were compared with those of the 793 patients commencing chemotherapy > or= 21 days after surgery ( group B ) . Median follow-up time was 39 months ( range , 12 to 147 months ) . RESULTS No significant difference in 5-year DFS was found between the two groups overall ( 70 % for group A v 72 % for group B ; P = .4 ) or in any subgroup . Likewise , there was no difference in 5-year OS ( 82 % for group A v 84 % for group B ; P = .2 ) or when the interval to the start of chemotherapy was considered as a continuous variable ( P = .4 ) . CONCLUSION We have been unable to identify any significant survival benefit from starting adjuvant chemotherapy early after surgery , either overall or in any subset of patients BACKGROUND Neither chemotherapy with a single-alkylating agent nor aggressive combination chemotherapy cures advanced stage low- grade non-Hodgkin lymphomas , even when combined with radiotherapy . Our aim was to compare administration of immediate chlorambucil treatment with a policy of delaying chlorambucil until clinical progression necessitated its use , in asymptomatic patients with advanced-stage , low- grade non-Hodgkin lymphoma . METHODS 309 patients with asymptomatic , advanced-stage , low- grade non-Hodgkin lymphomas were recruited from 44 UK centres between Feb 1 , 1981 , and July 31 , 1990 . 158 patients were r and omised to receive immediate systemic therapy with oral chlorambucil 10 mg per day continuously . The remaining 151 were r and omised to an initial policy of observation , with systemic therapy delayed until disease progression . In both groups , local radiotherapy to symptomatic nodes was allowed . FINDINGS Median length of follow-up was 16 years . Overall survival or cause-specific survival did not differ between the two groups ( median overall survival for oral chlorambucil 5.9 [ range 0 - 17.8 ] years and for observation 6.7 [ 0.5 - 18.9 ] years , p=0.84 ; median cause-specific survival 9 [ 0 - 17.8 ] years and 9.1 [ 0.67 - 18.9 ] years , respectively p=0.44 ) . In a multivariate analysis , age younger than 60 years , erythrocyte sedimentation rate ( ESR ) 20 mm/h or less , and stage III disease , conferred significant advantages in both overall survival ( p<0.0001 , 0.03 , and 0.03 , respectively ) and cause-specific survival ( p=0.002 , 0.008 , and 0.001 , respectively ) . In the observation group , at 10 years ' follow-up , 19 patients were alive and had not received chemotherapy . The actuarial chance of not needing chemotherapy ( non-lymphoma deaths censored ) at 10 years was 19 % ( 40 % if older than 70 years ) . INTERPRETATION An initial policy of watchful waiting in patients with asymptomatic , advanced stage low- grade non-Hodgkin lymphoma is appropriate , especially in patients older than age 70 years BACKGROUND Surgery is the primary treatment for patients with stage I , II , or IIIA non-small-cell lung cancer ( NSCLC ) . However , long-term survival of NSCLC patients after surgery alone is largely unsatisfactory , and the role of adjuvant chemotherapy in patient survival has not yet been established . METHODS Between January 1994 and January 1999 , 1209 patients with stage I , II , or IIIA NSCLC were r and omly assigned to receive mitomycin C ( 8 mg/m2 on day 1 ) , vindesine ( 3 mg/m2 on days 1 and 8) , and cisplatin ( 100 mg/m2 on day 1 ) every 3 weeks for three cycles ( MVP group ; n = 606 ) or no treatment ( control group ; n = 603 ) after complete resection . R and omization was stratified by investigational center , tumor size , lymph-node involvement , and the intention to perform radiotherapy . The primary endpoint was overall survival and secondary endpoints were progression-free survival and toxicity associated with adjuvant treatment . Survival curves were analyzed using the log-rank test . All statistical tests were two-sided . RESULTS After a median follow-up time of 64.5 months , there was no statistically significant difference between the two patient groups in overall survival ( hazard ratio = 0.96 , 95 % confidence interval = 0.81 to 1.13 ; P = .589 ) or progression-free survival ( hazard ratio = 0.89 , 95 % confidence interval = 0.76 to 1.03 ; P = .128 ) . Only 69 % of patients received the three planned cycles of MVP . Grade s 3 and 4 neutropenia occurred in 16 % and 12 % , respectively , of patients in the MVP arm . Radiotherapy was completed by 65 % of patients in the MVP arm and by 82 % of patients in the control group . In the multivariable analysis , only disease stage and sex were associated with survival . CONCLUSION This r and omized trial failed to prospect ively confirm a statistically significant role for adjuvant chemotherapy in completely resected NSCLC . Given the poor compliance with the MVP regimen used in this study , future studies should explore more effective treatments The data from two prospect i ve r and omised phase III trials that were initiated by the West Midl and s Ovarian Cancer Study Group ( WMOCSG ) in 1981 and 1986 , recruiting 167 and 195 patients respectively , have been pooled and the survival patterns of the 362 Output:	However , increased TTC may have a negative prognostic impact , and delays beyond 4 weeks should be avoided . Timing of chemotherapy for metastatic colorectal cancer does not influence survival . The optimal timing of chemotherapy in lung cancer is unclear ; however , rapid tumour growth and poor disease prognosis suggest that delays should be avoided wherever possible . The optimal timing of chemotherapy in ovarian cancer is unclear as available studies are of low level , report inconsistent results and are limited to the post-surgery setting ; however , increased TTC may have a negative prognostic impact ; therefore , delays beyond 4 weeks should be avoided
MS21214	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: A r and omised controlled trial has been conducted into the effects of discharging patients from hospital either 48 hours or six to seven days after operations for inguinal hernia and varicose veins . There was no statistically significant difference in major postoperative complications between the two lengths of stay for either of the two conditions . Similarly there was no difference between the two groups of hernia patients in relation to eventual recurrences . There was no significant difference in length of convalescence between long-stay and short-stay patients in full-time occupations . The savings to the statutory services of discharging patients early were estimated at 25.72 pounds per patient . Patients appeared to approve of the type of care they experienced , regardless of length of stay . However , the families of short-stay patients were significantly less enthusiastic in their attitudes towards the policy of early discharge than the families of long-stay patients All admissions to a 1,100-bed Department of Veterans Affairs ( VA ) hospital were screened to identify 171 terminally ill patients with informal caregivers who were then r and omly assigned to VA hospital-based team home care ( HBHC , N = 85 ) or customary care ( N = 86 ) . Patient functioning , and patient and caregiver morale and satisfaction with care were measured at baseline , one month , and six months . Health services utilization was monitored over the six-month study period and converted to cost . Findings included no differences in patient survival , activities of daily living ( ADL ) , cognitive functioning , or morale , but a significant increase in patient ( p = .02 ) and caregiver ( p = .005 ) satisfaction with care at one month . A substitution effect of HBHC was seen . Those in the experimental group used 5.9 fewer VA hospital days ( p = .03 ) , result ing in a $ 1,639 or 47 percent per capita saving in VA hospital costs ( p = .02 ) . As a result , total per capita health care costs , including HBHC , were $ 769 or 18 percent ( n.s . ) lower in the HBHC sample , indicating that expansion of VA HBHC to serve terminally ill veterans would increase satisfaction with care at no additional cost The community health services in Southern Derbyshire , in conjunction with an acute hospital , established a pilot scheme for the early discharge of fractured neck of femur patients from hospital to their own homes . The scheme was evaluated by prospect ively comparing a group of patients using Hospital at Home ( HAH ) and a group receiving hospital care only . The main outcomes measured were the proportion of hospital admissions for fractured neck of femur using HAH , length of stay , patient satisfaction , general health status at discharge as measured by the Nottingham Health Profile , and three-month mortality and readmission rates . Costs were calculated based on prices charged by providers of the services . In the first year of the scheme , 76 ( 18 per cent ) of the 432 hospital admissions for fractured neck of femur fitted the selection criteria and agreed to admission to HAH . Thirty-four patients were identified who were suitable for HAH but not admitted to it . The comparison of the 76 HAH patients and 34 hospital patients revealed that HAH patients were discharged from hospital an average of 7 days earlier ; patients in both groups were satisfied with the care they received ; the general health status of the two groups at discharge was similar , with the exception that HAH patients had better emotional health on discharge from care ; the three-month mortality rate was similar in both groups ( 5 per cent ) ; the readmission rate for HAH patients appeared higher than for hospital patients but this difference was not statistically significant ( 15.8 per cent versus 8.8 per cent , Fisher 's exact test , p = 0.187 ) . ( ABSTRACT TRUNCATED AT 250 WORDS The purpose of this study was to evaluate the impact of a primary home care intervention program on patient outcomes after selected patients were discharged from a short-stay hospital . R and om assignment of 249 frail , elderly patients was made to a group provided with physician-led primary home care , and home assistance service on a 24-hour basis , or to a control group given st and ard care . At r and omization , patients were considerably disabled , had a mean age of 80.5 years , and had a high likelihood of long-stay hospital care . Medical and functional data were essentially the same at baseline for both groups . At 6-months follow-up , significant improvement in instrumental activities of daily living ( P = 0.04 ) and outdoor walking ( P = 0.03 ) , and medical condition was found in the primary care intervention group compared with the controls and less utilization of long-stay hospital facilities was displayed in the team patients ( P < 0.001 ) than in the controls . A selection of elderly , dependent patients can be cared for in their homes after short-stay hospital discharge and benefit from this primary home care intervention program in terms of improved medical and functional outcomes and less long-stay hospitalization The rehabilitation of elderly patients after hip fractures is important : we report a prospect i ve study which compares supported home rehabilitation with management in hospital in two similar groups of patients . Our results show that early discharge from hospital and home rehabilitation produces substantial savings in bed days , and also provides quicker and more effective recovery In a controlled trial of a home-care service available for the first 6 months after acute stroke , 440 patients received the new service and 417 patients were in the control group . The trial group used more hospital bed days , had a slightly higher admission rate , and did not show better emotional adjustment to stroke than the control group . There was no difference between the 2 groups in stress on relatives . Functional recovery was equal in the 2 groups . A quarter of patients managed at home in each group were severely disabled . Providing a new service does not necessarily alter clinical decisions in the short term , and care should be taken before exp and ing domiciliary services to reduce hospital use The opinions of patients and of caring persons ( usually relatives ) were sought in this trial of different methods of providing care for 360 patients after operations for hernia or varicose veins . Analysis of patients ' opinions suggested that day care was the most acceptable of the three types of care examined . The reactions of caring persons did not reveal any major criticisms or disadvantages Alternative systems of care after operations for varicose veins or hernia were compared in a total of 360 selected patients , of whom 121 were allocated to be managed in an acute ward for 48 h , 122 in a convalescent hospital for 48 h and 117 to be discharged directly home to the care of the district nursing sister and general practitioner . There were no deaths or major complications . Anaesthetic or surgical problems caused 5 patients ( 3 convalescent and 2 day care ) to be retained in hospital on the day of operation . Minor complications were recorded in approximately one‐third of the patients . The majority of these were effectively dealt with by the district nursing sister and only one‐third of the complications needed the attention of the general practitioner . Two of the ward patients and 1 of the convalescent patients required readmission to hospital ( 1 per cent in all ) . No significant difference was demonstrated in the medical outcome between the three groups after operation . Day care was the most economical of the three systems of care . Inquiry into the patients ' opinions elicited the highest proportion of favourable responses in the day care group The Home Treatment Team ( HTT ) , a hospital discharge team for elderly patients , was created to provide practical help and promote independence of patients at home for up to 6 weeks after hospital discharge . Patients were those judged to be at particular risk of failing to resettle , and thus being readmitted to hospital or admitted to a residential or nursing home . An open r and omized controlled trial compared patients receiving the HTT ( n = 29 ) with controls ( n = 25 ) receiving appropriate conventional community services . Fewer HTT patients were readmitted ( four by 6 weeks and nine by 12 weeks ) than controls ( nine by 6 weeks and 14 by 12 weeks , p < 0.05 ) and more were at home at 6 weeks ( 24 , 83 % and 10 , 40 % , p < 0.05 ) , 12 weeks ( 21 , 72 % and 11 , 44 % , p < 0.05 ) and 12 months ( 17 , 58 % and 10 , 40 % , p < 0.05 ) . The HTT group spent fewer days in hospital than controls during 12 weeks ( median difference 34 days , 95 % confidence interval 0 - 75 , p < 0.05 ) and more days at home during 12 months ( 90 ; 247 - 0 , p = 0.02 ) . Neither group showed any significant change in mental state or functional abilities over 12 weeks . Potentially confounding factors were considered insufficient explanation for the difference in outcome between the groups . It is concluded that the HTT was of benefit but the mechanism of its effect was not identified Output:	Patients discharged early from hospital to hospital at home following elective surgery expressed greater satisfaction with care than those who remained in hospital . Carers , however , expressed less satisfaction with hospital at home compared with hospital care . No statistically significant difference was detected for overall net health costs . CONCLUSIONS This review does not support the widespread adoption of hospital at home , nor the discontinuation of existing schemes for elderly medical patients , patients who have had elective surgery , or those with a terminal illness . There is insufficient evidence to determine the effect of hospital at home on patient outcomes , or cost to the health service
MS21215	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Insulin pump therapy ( continuous subcutaneous insulin infusion [ CSII ] ) and multiple daily injections ( MDIs ) with insulin glargine as basal insulin and mealtime insulin lispro have not been prospect ively compared in people naïve to either regimen in a multicenter study . We aim ed to help close that deficiency . RESEARCH DESIGN AND METHODS People with type 1 diabetes on NPH-based insulin therapy were r and omized to CSII or glargine-based MDI ( both otherwise using lispro ) and followed for 24 weeks in an equivalence design . Fifty people were correctly r and omized , and 43 completed the study . RESULTS Total insulin requirement ( mean ± SD ) at end point was 36.2 ± 11.5 units/day on CSII and 42.6 ± 15.5 units/day on MDI . Mean A1C fell similarly in the two groups ( CSII −0.7 ± 0.7 % ; MDI −0.6 ± 0.8 % ) with a baseline-adjusted difference of −0.1 % ( 95 % CI −0.5 to 0.3 ) . Similarly , fasting blood glucose and other prepr and ial , postpr and ial , and nighttime self-monitored plasma glucose levels did not differ between the regimens , nor did measures of plasma glucose variability . On CSII , 1,152 hypoglycemia events were recorded by 23 of 28 participants ( 82 % ) and 1,022 in the MDI group by 27 of 29 patients ( 93 % ) ( all hypoglycemia differences were nonsignificant ) . Treatment satisfaction score increased more with CSII ; however , the change in score was similar for the groups . Costs were ∼3.9 times higher for CSII . CONCLUSIONS In unselected people with type 1 diabetes naïve to CSII or insulin glargine , glycemic control is no better with the more expensive CSII therapy compared with glargine-based MDI therapy OBJECTIVE Multiple daily injection ( MDI ) therapy of bolus insulin aspart and basal insulin glargine was compared with continuous subcutaneous insulin infusion ( CSII ) with aspart in type 1 diabetic patients previously treated with CSII . RESEARCH DESIGN AND METHODS One hundred patients were enrolled in a r and omized , multicenter , open-label , crossover study . After a 1-week run-in period with aspart by CSII , 50 subjects were r and omly assigned to MDI therapy ( aspart immediately before each meal and glargine at bedtime ) and 50 subjects continued CSII . After 5 weeks of the first treatment , subjects crossed over to the alternate treatment for 5 weeks . During the last week of each treatment period , subjects wore a continuous glucose monitoring system for 48 - 72 h. RESULTS Mean serum fructosamine levels were significantly lower after CSII therapy than after MDI therapy ( 343 + /- 47 vs. 355 + /- 50 micromol/l , respectively ; P = 0.0001 ) . Continuous glucose monitoring profiles over a 24-h time period showed that glucose exposure was 24 and 40 % lower for CSII than MDI as measured by area under the curve ( AUC ) glucose > /=80 mg/dl ( 1,270 + /- 742 vs. 1,664 + /- 1,039 mg . h . dl(-1 ) ; P < 0.001 ) and AUC glucose > /=140 mg/dl ( 464 + /- 452 vs. 777 + /- 746 mg . h . dl(-1 ) , CSII vs. MDI , respectively ; P < 0.001 ) . Similar percentages of subjects reported hypoglycemic episodes ( CSII : 92 % , MDI : 94 % ) and nocturnal ( 12:00 a.m. to 8:00 a.m. ) hypoglycemic episodes ( CSII : 73 % , MDI : 72 % ) . Major hypoglycemia was infrequent ( CSII : two episodes , MDI : five episodes ) . CONCLUSIONS In a trial of short duration , CSII therapy with insulin aspart result ed in lower glycemic exposure without increased risk of hypoglycemia , as compared with MDI with insulin aspart and glargine OBJECTIVE Effects of pump treatment vs. four times daily injections were explored in children with diabetes with regard to quality of life and impact of disease as well as adverse effects and parameters of metabolic control . METHODS An open , parallel , r and omized controlled prospect i ve comparative study lasting 14 months was completed by 38 type 1 children with diabetes ( age 4 - 16 yr ) following a 3.5-months run-in phase . St and ardized quality -of-life Pediatric Quality of life Inventory ( PedsQL ) and impact of disease scores were obtained every 3.5 months as well as regular medical parameters . Parallel treatment group data and longitudinal within-patient data were analysed for each treatment modality . RESULTS Within-patient comparisons of the two treatment modalities showed significant improvement in PedsQL and impact scores after pump treatment . Treatment group comparisons did not show significant improvement . Pump treatment result ed in decreased symptomatic hypoglycaemia and lowered haemoglobin A1c by 0.22 % after run in . CONCLUSIONS Within-patient comparison suggests that metabolic control , frequency of severe hypoglycaemia ( a threefold decrease ) , quality of life and impact of disease scores are improved by pump treatment in comparison to regular treatment with four daily insulin injections AIMS The goal of the study was to determine whether continuous subcutaneous insulin infusion ( CSII ) differs from a multiple daily injection ( MDI ) regimen based on neutral protamine hagedorn ( NPH ) as basal insulin with respect to glycaemic control and quality of life in people with Type 1 diabetes . METHODS The 5-Nations trial was a r and omized , controlled , crossover trial conducted in 11 European centres . Two hundred and seventy-two patients were treated with CSII or MDI during a 2-month run-in period followed by a 6-month treatment period , respectively . The quality of glycaemic control was assessed by HbA(1c ) , blood glucose values , and the frequency of hypoglycaemic events . For the evaluation of the quality of life , three different self-report question naires have been assessed . RESULTS CSII treatment result ed in lower HbA(1c ) ( 7.45 vs. 7.67 % , P < 0.001 ) , mean blood glucose level ( 8.6 vs. 9.4 mmol/l , P < 0.001 ) and less fluctuation in blood glucose levels than MDI ( + /- 3.9 vs. + /- 4.3 mmol/l , P < 0.001 ) . There was a marked reduction in the frequency of hypoglycaemic events using CSII compared with MDI , with an incidence ratio of 1.12 [ 95 % confidence interval ( CI ) : 1.08 - 1.17 ] and 2.61 ( 95 % CI : 1.59 - 4.29 ) for mild and severe hypoglycaemia , respectively . The overall score of the diabetes quality of life question naire was higher for CSII ( P < 0.001 ) , and an improvement in pump users ' perception of mental health was detected when using the SF-12 question naire ( P < 0.05 ) . CONCLUSION CSII usage offers significant benefits over NPH-based MDI for individuals with Type 1 diabetes , with improvement in all significant metabolic parameters as well as in patients ' quality of life . Additional studies are needed to compare CSII with glargine- and detemir-based MDI 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 Recently developed technologies for the treatment of type 1 diabetes mellitus include a variety of pumps and pumps with glucose sensors . METHODS In this 1-year , multicenter , r and omized , controlled trial , we compared the efficacy of sensor-augmented pump therapy ( pump therapy ) with that of a regimen of multiple daily insulin injections ( injection therapy ) in 485 patients ( 329 adults and 156 children ) with inadequately controlled type 1 diabetes . Patients received recombinant insulin analogues and were supervised by expert clinical teams . The primary end point was the change from the baseline glycated hemoglobin level . RESULTS At 1 year , the baseline mean glycated hemoglobin level ( 8.3 % in the two study groups ) had decreased to 7.5 % in the pump-therapy group , as compared with 8.1 % in the injection-therapy group ( P<0.001 ) . The proportion of patients who reached the glycated hemoglobin target ( < 7 % ) was greater in the pump-therapy group than in the injection-therapy group . The rate of severe hypoglycemia in the pump-therapy group ( 13.31 cases per 100 person-years ) did not differ significantly from that in the injection-therapy group ( 13.48 per 100 person-years , P=0.58 ) . There was no significant weight gain in either group . CONCLUSIONS In both adults and children with inadequately controlled type 1 diabetes , sensor-augmented pump therapy result ed in significant improvement in glycated hemoglobin levels , as compared with injection therapy . A significantly greater proportion of both adults and children in the pump-therapy group than in the injection-therapy group reached the target glycated hemoglobin level . ( Funded by Medtronic and others ; Clinical Trials.gov number , NCT00417989 . 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 Output:	There was no significant difference in minor or severe hypoglycemic events . Continuous subcutaneous insulin infusion was associated with lower incidence of nocturnal hypoglycemia . There was no significant difference in the time spent in hypoglycemia . In children and adults with type 1 diabetes and compared to multiple daily injections , continuous subcutaneous insulin infusion is associated with a modest reduction in glycosylated hemoglobin . There was no difference in severe or minor hypoglycemia , but likely a lower incidence of nocturnal hypoglycemia with continuous subcutaneous insulin infusion
MS21216	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Control of oral anticoagulation therapy has been reported to often be inadequate . Previous retrospective investigations suggest that patients ' self-adjustment of oral anticoagulants may lead to improved control . OBJECTIVE To investigate the effects of patients ' self-management of oral anticoagulation therapy on accuracy of control and measures of treatment-related quality of life . DESIGN R and omized , single-blind , multicenter trial . SETTING AND PARTICIPANTS A total of 179 patients receiving long-term oral anticoagulation treatment were enrolled at 5 referral centers in Germany . INTERVENTION Patients were r and omized to an oral anticoagulation self-management group based on a structured treatment and teaching program and international normalized ratio ( INR ) self-monitoring . The control group received conventional care as provided by family physicians , including referral to specialists if necessary . MAIN OUTCOME MEASURES Deviation of INR values from the individual INR target range ( squared ) and the 5 categories of treatment-related quality of life . RESULTS Deviation of INR value from the mean of the INR target range was significantly lower in the intervention group at 3-month ( squared INR deviation , 0.59 vs 0.95 ; P<.001 ) and 6-month follow-up ( 0.65 vs 0.83 ; P=.03 ) compared with the control group . Also , the intervention group had INR values within the target range more often ( repeated measurement analysis for categorical data , P=.006 ) . The results were mainly due to less frequent suboptimal INR values in the intervention group ( 32.8 % vs 50.0 % [ P=.03 ] at 3-month , and 33.7 % vs 48.2 % [ P=.08 ] at 6-month follow-up ) . Treatment-related quality -of-life measures , especially treatment satisfaction scores , were significantly higher in the intervention group compared with controls . CONCLUSIONS An anticoagulation education program that includes self-management of anticoagulation therapy results in improved accuracy of anticoagulation control and in treatment-related quality -of-life measures . Further studies are needed to describe whether the program will reduce risk of bleeding or thromboembolism AIMS In Belgium , general practitioners ( GPs ) mainly manage oral anticoagulation therapy . To improve the quality of oral anticoagulation management by GPs and to compare different models and interventions , a r and omized clinical trial was performed . METHODS AND RESULTS Stratified r and omization divided 66 GP- practice s into four groups . A 6-month retrospective analysis assessed the baseline quality . In the prospect i ve study , each group received education on oral anticoagulation , anticoagulation files , and patient information booklets ( groups A , B , C , and D ) . Group B additionally received feedback every 2 months on their anticoagulation performance ; group C determined the international normalized ratio ( INR ) with a CoaguChek device in the doctor 's office or at the patient 's home ; and group D received Dawn AC computer assisted advice for adapting oral anticoagulation . For the different groups , the time spent in target INR range ( Rosendaal 's method ) and adverse events related to anticoagulation were determined and compared with the same quality indicators at baseline . There was a significant increase in per cent of time within 0.5 INR from target , from 49.5 % at baseline to 60 % after implementing the different interventions . However , neither the per cent in target range nor the event rates differed among the four groups . CONCLUSION The interventions significantly improved the quality of management of oral anticoagulation by Belgian GPs , mainly as a result of an education and support programme Background : The increase in numbers of patients receiving warfarin treatment has led to the development of alternative models of service delivery for oral anticoagulant monitoring . Patient self management for oral anticoagulation is a model new to the UK . This r and omised trial was the first to compare routine primary care management of oral anticoagulation with patient self management . Aim : To test whether patient self management is as safe , in terms of clinical effectiveness , as primary care management within the UK , as assessed by therapeutic international normalised ratio ( INR ) control . Method : Patients receiving warfarin from six general practice s who satisfied study entry criteria were eligible to enter the study . Eligible patients were r and omised to either intervention ( patient self management ) or control ( routine primary care management ) for six months . The intervention comprised two training sessions of one to two hours duration . Patients were allowed to undertake patient self management on successful completion of training . INR testing was undertaken using a Coaguchek device and regular internal/external quality control tests were performed . Patients were advised to perform INR tests every two weeks , or weekly if a dose adjustment was made . Dosage adjustment was undertaken using a simple dosing algorithm . Results : Seventy eight of 206 ( 38 % ) patients were eligible for inclusion and , of these , 35 ( 45 % ) declined involvement or withdrew from the study . Altogether , 23 intervention and 26 control patients entered the study . There were no significant differences in INR control ( per cent time in range : intervention , 74 % ; control , 77 % ) . There were no serious adverse events in the intervention group , with one fatal retroperitoneal haemorrhage in the control group . Costs of patient self management were significantly greater than for routine care ( £ 90 v £ 425/patient/year ) . Conclusion : These are the first UK data to demonstrate that patient self management is as safe as primary care management for a selected population . Further studies are needed to eluci date whether this model of care is suitable for a larger population BACKGROUND Vitamin K antagonist treatment is effective for prevention and treatment of thromboembolic events but frequent laboratory control and dose-adjustment are essential . Small portable devices have enabled patient self-monitoring of anticoagulation and self-adjustment of the dose . We compared this self-management of oral anticoagulant therapy with conventional management by a specialist anticoagulation clinic in a r and omised cross-over study . METHODS 50 patients on long-term oral anticoagulant treatment were included in a r and omised controlled crossover study . Patients were self-managed or were managed by the anticoagulation clinic for a period of 3 months . After this period the alternative strategy was followed for each patient . Prothrombin time ( expressed as international normalised ratio [ INR ] ) were measured at intervals of 1 - 2 weeks in both periods without knowledge of type of management . The primary endpoint was the number of measurements within the therapeutic range ( therapeutic target value + /-50.5 INR units ) . FINDINGS There was no significant difference in the overall quality of control of anticoagulation between the two study periods . Patients were for 55 % and for 49 % of the treatment period within a range of + /-0.5 from the therapeutic target INR during self-management and anticoagulation clinic management , respectively ( p=0.06 ) . The proportion of patients who spent most time in the therapeutic target range was larger during self-management than during anticoagulation clinic-guided management . The odds ratio for a better control of anticoagulation ( defined as the period of time in the therapeutic target range ) during self-management compared with anticoagulation clinic-guided management was 4.6 ( 95 % CI 2.1 - 10.2 ) . A patient-satisfaction assessment showed superiority of self-management over conventional care . INTERPRETATION Self-management of INR in the population in this study is feasible and appears to result in control of anticoagulation that is at least equivalent to management by a specialist anticoagulation clinic . It is also better appreciated by patients . Larger studies are required to assess the effect of this novel management strategy on the incidence of thromboembolic or bleeding complications BACKGROUND Self-management ( SM ) of warfarin by patients is an attractive strategy , particularly if it improves anticoagulation control and can be done safely under minimal physician supervision . OBJECTIVE To compare the effect of SM with physician-management ( PM ) on the maintenance of therapeutic anticoagulation . METHODS A r and omized , open-label eight-month trial was performed . Patients 18 years of age and older were eligible if they were receiving warfarin for at least one month before enrolment and required anticoagulation for at least one year to a target international normalized ratio ( INR ) of 2.0 to 3.0 or 2.5 to 3.5 . Exclusion criteria were a known hypercoaguable disorder , mental incompetence , a language barrier or an inability to attend training sessions . Patients r and omly assigned to SM tested their INR using a point-of-care device ( Pro Time Microcogulation System , International Technidyne Corporation , USA ) and adjusted their warfarin doses using a nomogram . Patients r and omly assigned to PM received usual care from their general practitioner . The primary outcome was to demonstrate 20 % improvement in anticoagulation control by SM . RESULTS One hundred forty patients were r and omly assigned ( 70 per group ) . Thirteen patients dropped out of SM early due to an inability to self-manage . Based on intention-to-treat analysis , there was no difference in the proportion of INR in range ( SM 64.8 % versus PM 58.7 % , P=0.23 ) or time in target range ( SM 71.8 % versus PM 63.2 % , P=0.14 ) . Patients managing their own therapy spent less time below the therapeutic range ( 15.0 % versus 27.3 % , P=0.04 ) . There were three major complications of thrombosis or bleeding , all occurring in the PM arm . All patients who completed SM preferred to continue with that strategy . CONCLUSIONS SM was not significantly better than PM in maintaining therapeutic anticoagulation . SM was feasible and appeared safe in the present study population Background Antithrombotic treatment is a continuous therapy that is often performed in general practice and requires careful safety management . The aim of this study is to investigate whether a best- practice model that applies major elements of case management and patient education , can improve antithrombotic management in primary healthcare in terms of reducing major thromboembolic and bleeding events . Methods This 24-month cluster-r and omized trial will be performed with 690 adult patients from 46 practice s. The trial intervention will be a complex intervention involving general practitioners , healthcare assistants , and patients with an indication for oral anticoagulation . To assess adherence to medication and symptoms in patients , as well as to detect complications early , healthcare assistants will be trained in case management and will use the Coagulation-Monitoring List ( Co-MoL ) to regularly monitor patients . Patients will receive information ( leaflets and a video ) , treatment monitoring via the Co-MoL and be motivated to perform self-management . Patients in the control group will continue to receive treatment as usual from their general practitioners . The primary endpoint is the combined endpoint of all thromboembolic events requiring hospitalization and all major bleeding complications . Secondary endpoints are mortality , hospitalization , strokes , major bleeding and thromboembolic complications , severe treatment interactions , the number of adverse events , quality of anticoagulation , health-related quality of life , and costs . Further secondary objectives will be investigated to explain the mechanism by which the intervention is effective : patients ’ assessment of chronic illness care , self-reported adherence to medication , general practitioners ’ and healthcare assistants ’ knowledge , and patients ’ knowledge and satisfaction with shared decision making . Practice recruitment is expected to take place between July and December 2012 . Recruitment of eligible patients will start in July 2012 . Assessment will occur at three time points : baseline and follow-up after 12 months and after 24 months . Discussion The efficacy and effectiveness of individual elements of the intervention , such as antithrombotic interventions , self-management concepts in orally anticoagulated patients , and the method ological tool of case management , have already been extensively demonstrated . This project foresees the combination of several proven instruments , as a result of which we expect to profit from a reduction in the major complications associated with antithrombotic treatment . Trial registration Current Controlled Trials IS RCT Background Self management of oral anticoagulation ( OAC ) decreases complication rates and improves quality of life . Manual and cognitive abilities of patients and patient training in a structured format are a precondition for this concept . Up to now , there is no evidence about knowledge increase from teaching programs . Methods Seventy-six patients ( mean age , 57.4 years , 71 % male ) who started long-term OAC were included in the prospect i ve multi-center study at three teaching centers representing different population s of anticoagulation patients : a department of cardiovascular surgery , an inpatient rehabilitation center and an anticoagulation clinic . The patients were trained in a structured education program for two days . For the evaluation , the patients performed st and ardized tests including 16 questions prior to start ( T0 ) , after each training unit ( T1/T2 ) and 6 weeks later ( T3 ) . The primary endpoint was the percentage of > 75 % of patients who could answer > 50 % of questions correctly at T3 . Secondary endpoints were the overall and item-specific percentages of correct answers at the end of each training unit ( T1 , T2 ) and at T3 . In addition , the teaching program was rated by the patients on a six-point rating scale . Results Seventy-four out of 76 patients gave at least 50 % correct answers at T3 ( 97.4 % ; 95 % confidence interval , 90.8–99.7 % ) . The average rates of correct answers developed from 40 % ( T0 ) , 86 % ( T1 ) , 94 % ( T2 ) to 96 % ( T3 ) . The greatest increase of knowledge was observed with blood components , interpretation of International Normalized Ratio ( INR ) value , and the interaction of anticoagulation with other variables ( e.g. drugs or infection ) Output:	None of the review articles revealed any difference in the frequency of severe hemorrhagic events . Adults with an indication for long-term oral anticoagulation benefit from self-management , as compared to st and ard treatment with management of dosing by a physician .
MS21217	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND The effect of conventional allergen immunotherapy on allergen-specific T lymphocyte cytokine production is incompletely understood , particularly during the initial phase of treatment . OBJECTIVE The purpose of this study was to prospect ively follow the kinetics of change in CD4(+ ) T cell cytokine secretion during the course of conventional immunotherapy . METHODS Six allergic individuals were treated with extracts of Dermatophagoides farinae/Dermatophagoides pteronyssinus or with rye grass pollen ( Lolium perenne ) allergen , but not both , by using an internally controlled conventional immunotherapy protocol . CD4(+ ) T cells from peripheral blood were examined in vitro at varying intervals after the initiation of immunotherapy by stimulation with D farinae or L perenne group I antigen . The quantity of IL-4 and IFN-gamma produced and its relationship to clinical improvement was determined . RESULTS The ratio of allergen-specific IL-4/IFN-gamma production by CD4(+ ) T cells from 4 of 6 individuals receiving immunotherapy greatly increased during the period when the dose of allergen was increasing . However , after high-dose maintenance therapy was achieved , this ratio decreased in subjects responding clinical ly to , but not in those failing , immunotherapy . In addition , late-phase skin reactions and allergen-specific IgE levels in responding , but not in nonresponding , subjects diminished over the course of immunotherapy . CONCLUSION Conventional immunotherapy may initially exacerbate allergic disease by increasing allergen-specific IL-4 and allergen-specific IgE production . Later clinical improvement is associated with a reduction in allergen-specific IL-4 production and in allergen-specific serum Allergic rhinitis and asthma are examples of allergic airways disease . Despite their differing symptomatology , both disorders affect the mucosal lining of the respiratory tract and are linked by common underlying cellular processes , thus , using the ‘ united airways ’ approach , they can be considered part of the same allergic disease . The conditions are often comorbid , and there is evidence to suggest that allergic rhinitis in children is a significant risk factor for subsequent development of asthma . Management strategies that target the underlying cause of allergic rhinitis in children have the potential to offer additional symptom control above that of symptomatic medications , and prevent disease progression . Specific immunotherapy ( SIT ) is the only currently available treatment that is proven to target the disease in this way . SIT affects the underlying cause of allergic rhinitis , producing changes in antibody responses to allergens . It has been shown to be effective in the reduction of allergic rhinitis symptoms in both children and adults , with effects being sustained for several years after treatment completion . Furthermore , a number of trials provide evidence that SIT may prevent the development of new sensitisations and asthma in children and adults with allergic rhinitis . One such open-label , r and omised controlled study in children/adolescents ( the Preventive Allergy Treatment Study ) showed that significantly fewer patients who received 3 years of SIT for grass/birch pollen-induced allergic rhinitis had developed asthma 10 years after treatment initiation versus controls . Some clinical guidelines acknowledge this potential asthma preventive effect in children and the need for additional data from double-blind , placebo-controlled trials to support these findings Twenty‐seven patients with allergy to house‐dust mite and the clinical symptoms of perennial rhinitis and /or mild asthma were treated with specific immunotherapy ( SIT ) with st and ardized extracts of house‐dust mite for 3 years . The success of therapy was evaluated in yearly intervals OBJECTIVES This report presents health statistics from the 2001 National Health Interview Survey for the civilian noninstitutionalized adult population classified by sex , age , race and Hispanic origin , poverty status , and region of residence for chronic condition prevalence , health status and functional limitations , health care access and utilization , health behaviors , and human immunodeficiency virus ( HIV ) testing . Also , health statistics by education , income , health insurance coverage , marital status , and place of residence are presented for health status and limitations in activity , health care access and utilization , health behaviors , and knowledge and attitudes toward HIV . SOURCE OF DATA The National Health Interview Survey is a multistage probability sample survey conducted annually by interviewers of the U.S. Census Bureau for the Centers for Disease Control and Prevention 's National Center for Health Statistics and is representative of the civilian noninstitutionalized U.S. population . Sociodemographic data are collected for everyone in the family during face-to-face interviews with adults present at the time of the interview . The health information for adults in this report was obtained from one r and omly selected adult per family . HIGHLIGHTS In 2001 , 64 % of adults 18 years of age and over reported excellent or very good health . Fifty-eight percent of adults never participated in any type of vigorous leisure-time physical activity , and 13 % of adults did not have a usual place of health care . Twelve percent of adults had been told by a doctor or health professional that they had heart disease , and 21 % had been told on two or more visits that they had hypertension . Nearly a quarter of all adults were current smokers , and 22 % were former smokers . Based on estimates of body mass index , 36 % of adults were overweight and 23 % were obese INTRODUCTION In a double-blind , placebo-controlled trial ( EudraCT identifier : 2006 - 001795 - 20 ) , the st and ardised quality ( SQ ) house dust mite ( HDM ) sublingual immunotherapy (SLIT)-tablet ( ALK , Denmark ) was investigated . METHOD The trial included 604 subjects , ≥14 years , with mild-moderate HDM allergic asthma . Subjects were r and omised 1:1:1:1 to 1 , 3 or 6 SQ-HDM or placebo once daily . The primary endpoint was reduction in inhaled corticosteroid ( ICS ) after one year . ICS reduction , asthma quality of life question naire ( AQLQ ) and asthma control question naire ( ACQ ) score was analysed post hoc in a subgroup with daily ICS use of 400 - 800 μg and ACQ score of 1 - 1.5 , corresponding to partly controlled asthma ( N = 108 ) . RESULTS The trial met its primary endpoint . In the subgroup , the difference between placebo and 6 SQ-HDM in change from baseline in daily ICS use was 327 μg ( p < 0.0001 ) , while it was 0.52 ( p = 0.010 ) for AQLQ . The treatment effect on ICS reduction and AQLQ was increased for the subgroup versus the residual population ( ICS reduction : p < 0.001 ) ; AQLQ : p = 0.044 ) . CONCLUSION In this subgroup , including only patients with partly controlled asthma , the benefit of 1 year of treatment with SQ HDM SLIT-tablet was significantly higher than for the less severe full population , both in terms of increased asthma control and improved quality of life BACKGROUND Investigations meeting current st and ards are limited for the effect of house dust mite ( HDM ) allergy immunotherapy in asthmatic patients . OBJECTIVE This trial investigated the efficacy and safety of a st and ardized quality ( SQ ; allergen st and ardization method proprietary to the trial sponsor ) HDM SLIT-tablet ( ALK , Hørsholm , Denmark ) in adults and adolescents with HDM respiratory allergic disease . This publication reports the results of the endpoints related to asthma . METHODS Six hundred four subjects 14 years or older with HDM allergic rhinitis and mild-to-moderate asthma were r and omized 1:1:1:1 to double-blind daily treatment with one of 3 active doses ( 1 , 3 , or 6 SQ-HDM ) or placebo . Their use of inhaled corticosteroid ( ICS ) was st and ardized and adjusted at baseline and the end of treatment to the lowest dose providing asthma control . The primary end point was a reduction in ICS dose from the individual subject 's baseline dose after 1 year of treatment . RESULTS The primary analysis revealed a mean difference between 6 SQ-HDM and placebo in the reduction in daily ICS dose of 81 μg ( P = .004 ) . Relative mean and median reductions were 42 % and 50 % for 6 SQ-HDM and 15 % and 25 % for placebo , respectively . No statistically significant differences were observed for the other assessed asthma parameters , reflecting the intended controlled status of the trial subjects . The most common adverse events were local reactions in the mouth . The rate and severity of adverse events were higher for 3 and 6 SQ-HDM than for 1 SQ-HDM and placebo . CONCLUSION Efficacy in mild-to-moderate asthma of 6 SQ-HDM relative to placebo was demonstrated by a moderate statistically significant reduction in the ICS dose required to maintain asthma control . All active doses were well tolerated Although H1 antihistamine compounds ( H1 ) are highly effective in the treatment of allergic rhinitis ( AR ) , their role in the treatment of asthma is still controversial . Because a strong association between AR and bronchial hyperresponsiveness ( BHR ) has been reported , this study was design ed to assess the effect of a new H1 anti histamine , cetirizine ( C ) , on nonspecific BHR in patients with AR . Twelve patients were included in a double‐blind , crossover , placebo‐controlled trial . All patients had positive skin tests for common allergens and showed BHR to inhaled methacholine after specific nasal allergenic challenge . After a washout period of 1 week to ensure the stability of the BHR , the patients received , by crossover r and omization , C 10 mg daily or placebo ( P ) for 2 weeks . After each treatment period , BHR and nasal blocking index ( NBI ) were measured 1 and 6 h after nasal challenge . Bronchial responsiveness was expressed as methacholine PD20 , the provocation dose of methacholine causing a 20 % decrease in FEV1 . Measurements were then performed after 2 weeks of C and after 2 weeks of P. Baseline values of PD20 ( median ) measured before challenge showed no difference after cetirizine or after placebo ( 1.36 mg ) . Results 1 h after allergen did not show significant differences between C ( methacholine PD20=0.522 mg ) and placebo ( methacholine PD20=0.455 mg ) . By contrast , 6 h after challenge , methacholine PD20 was 0.918 mg for C and 0.483 mg for P ( P=0.042 ) . Similarly , NBI showed no change between C and P 1 h after challenge , whereas the difference was significant 6 h after challenge ( P=0.011 ) . These data demonstrate a protective nasal effect of C against BHR measured 6 h after nasal allergen challenge in patients with AR . They suggest that C may be useful in patients with asthma associated with AR The efficacy and safety of sublingual immunotherapy in house dust mite – induced asthma have yet to be firmly established . We report the results of a double‐blind , placebo‐controlled , r and omized clinical trial performed in mainl and China Output:	RECENT FINDINGS Recent clinical trials , systematic review s , and meta-analyses have demonstrated that allergen-specific immunotherapy ( ASI ) , especially sublingual immunotherapy for as short as 12 months , may help improve asthma symptoms and reduce medication usage . However , studies have not demonstrated overall improvement in pulmonary function tests despite improvement in symptoms . SUMMARY ASI may change the natural course of allergic asthma by reducing the risk of acute respiratory exacerbations and symptoms . Additional studies are necessary to examine whether early treatment of allergy sensitivities with ASI may ultimately prevent the progression to asthma
MS21218	*TASK* the task is to summarize an input biomedical literature in six sentences *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 U.S. Food and Drug Administration ( FDA ) is working to introduce new graphic warning labels for cigarette packages , the first change in cigarette warnings in more than 25 years . We sought to examine whether warnings discouraged participants from wanting to smoke and altered perceived likelihood of harms among adolescent males and whether these warning effects varied by age . Methods A national sample of 386 non-smoking American males ages 11–17 participated in an online experiment during fall 2010 . We r and omly assigned participants to view warnings using a 2 × 2 between-subjects design . The warnings described a harm of smoking ( addiction or lung cancer ) using text only or text plus an image used on European cigarette package warnings . Analyses tested whether age moderated the warnings ' impact on risk perceptions and smoking motivations . Results The warnings discouraged most adolescents from wanting to smoke , but lung cancer warnings discouraged them more than addiction warnings did ( 60 % vs. 34 % were “ very much ” discouraged , p<.001 ) . Including an image had no effect on discouragement . The warnings affected several beliefs about the harms from smoking , and age moderated these effects . Adolescents said addiction was easier to imagine and more likely to happen to them than lung cancer . They also believed that their true likelihood of experiencing any harm was lower than what an expert would say . Conclusions Our findings suggest that warnings focusing on lung cancer , rather than addiction , are more likely to discourage wanting to smoke among adolescent males and enhance their ability to imagine the harmful consequences of smoking . Including images on warnings had little effect on non-smoking male adolescents ' discouragement or beliefs , though additional research on the effects of pictorial warnings for this at-risk population is needed as the FDA moves forward with developing new graphic labels Objectives To compare adolescents ’ responses to three different styles of cigarette packaging : novelty ( br and ed packs design ed with a distinctive shape , opening style or bright colour ) , regular ( br and ed pack with no special design features ) and plain ( brown pack with a st and ard shape and opening and all br and ing removed , aside from br and name ) . Design Cross-sectional in-home survey . Setting UK . Participants R and om location quota sample of 1025 never smokers aged 11–16 years . Main outcome measures Susceptibility to smoking and composite measures of pack appraisal and pack receptivity derived from 11 survey items . Results Mean responses to the three pack types were negative for all survey items . However , ‘ novelty ’ packs were rated significantly less negatively than the ‘ regular ’ pack on most items , and the novelty and regular packs were rated less negatively than the ‘ plain ’ pack . For the novelty packs , logistic regressions , controlling for factors known to influence youth smoking , showed that susceptibility was associated with positive appraisal and also receptivity . For example , those receptive to the innovative Silk Cut Superslims pack were more than four times as likely to be susceptible to smoking than those not receptive to this pack ( AOR=4.42 , 95 % CI 2.50 to 7.81 , p<0.001 ) . For the regular pack , an association was found between positive appraisal and susceptibility but not with receptivity and susceptibility . There was no association with pack appraisal or receptivity for the plain pack . Conclusions Pack structure ( shape and opening style ) and colour are independently associated , not just with appreciation of and receptivity to the pack , but also with susceptibility to smoke . In other words , those who think most highly of novelty cigarette packaging are also the ones who indicate that they are most likely to go on to smoke . Plain packaging , in contrast , was found to directly reduce the appeal of smoking to adolescents Abstract Objective To compare the hazards of cigarette smoking in men who formed their habits at different periods , and the extent of the reduction in risk when cigarette smoking is stopped at different ages . Design Prospect i ve study that has continued from 1951 to 2001 . Setting United Kingdom . Participants 34 439 male British doctors . Information about their smoking habits was obtained in 1951 , and periodically thereafter ; cause specific mortality was monitored for 50 years . Main outcome measures Overall mortality by smoking habit , considering separately men born in different periods . Results The excess mortality associated with smoking chiefly involved vascular , neoplastic , and respiratory diseases that can be caused by smoking . Men born in 1900 - 1930 who smoked only cigarettes and continued smoking died on average about 10 years younger than lifelong non-smokers . Cessation at age 60 , 50 , 40 , or 30 years gained , respectively , about 3 , 6 , 9 , or 10 years of life expectancy . The excess mortality associated with cigarette smoking was less for men born in the 19th century and was greatest for men born in the 1920s . The cigarette smoker versus non-smoker probabilities of dying in middle age ( 35 - 69 ) were 42 % ν24 % ( a twofold death rate ratio ) for those born in 1900 - 1909 , but were 43 % ν 15 % ( a threefold death rate ratio ) for those born in the 1920s . At older ages , the cigarette smoker versus non-smoker probabilities of surviving from age 70 to 90 were 10 % ν 12 % at the death rates of the 1950s ( that is , among men born around the 1870s ) but were 7 % ν 33 % ( again a threefold death rate ratio ) at the death rates of the 1990s ( that is , among men born around the 1910s ) . Conclusion A substantial progressive decrease in the mortality rates among non-smokers over the past half century ( due to prevention and improved treatment of disease ) has been wholly outweighed , among cigarette smokers , by a progressive increase in the smoker ν non-smoker death rate ratio due to earlier and more intensive use of cigarettes . Among the men born around 1920 , prolonged cigarette smoking from early adult life tripled age specific mortality rates , but cessation at age 50 halved the hazard , and cessation at age 30 avoided almost all of it Cigarette package health warnings can be an important and low-cost means of communicating the health risks of smoking . We examined whether viewing health warnings in an experimental study influenced beliefs about the health effects of smoking , by conducting surveys with ~500 adult male smokers and ~500 male and female youth ( age 16–18 ) in Beijing , China ( n = 1070 ) , Mumbai area , India ( n = 1012 ) , Dhaka , Bangladesh ( n = 1018 ) , and Republic of Korea ( n = 1362 ) . Each respondent was r and omly assigned to view and rate pictorial health warnings for 2 of 15 different health effects , after which they reported beliefs about whether smoking caused 12 health effects . Respondents who viewed relevant health warnings ( vs. other warnings ) were significantly more likely to believe that smoking caused that particular health effect , for several health effects in each sample . Approximately three-quarters of respondents in China ( Beijing ) , Bangladesh ( Dhaka ) , and Korea ( which had general , text-only warnings ) thought that cigarette packages should display more health information , compared to approximately half of respondents in the Mumbai area , India ( which had detailed pictorial warnings ) . Pictorial health warnings that convey the risk of specific health effects from smoking can increase beliefs and knowledge about the health consequences of smoking , particularly for health effects that are lesser-known Objectives : To examine the impact of health warnings on smokers by comparing the short-term impact of new graphic ( 2006 ) Australian warnings with : ( i ) earlier ( 2003 ) United Kingdom larger text-based warnings ; ( ii ) and Canadian graphic warnings ( late 2000 ) ; and also to extend our underst and ing of warning wear-out . Methods : The International Tobacco Control Policy Evaluation Survey ( ITC Project ) follows prospect i ve cohorts ( with replenishment ) of adult smokers annually ( five waves : 2002–2006 ) , in Canada , United States , UK and Australia ( around 2000 per country per wave ; total n = 17 773 ) . Measures were of pack warning salience ( reading and noticing ) ; cognitive responses ( thoughts of harm and quitting ) ; and two behavioural responses : forgoing cigarettes and avoiding the warnings . Results : All four indicators of impact increased markedly among Australian smokers following the introduction of graphic warnings . Controlling for date of introduction , they stimulated more cognitive responses than the UK ( text-only ) changes , and were avoided more , did not significantly increase forgoing cigarettes , but were read and noticed less . The findings also extend previous work showing partial wear-out of both graphic and text-only warnings , but the Canadian warnings have more sustained effects than UK ones . Conclusions : Australia ’s new health warnings increased reactions that are prospect ively predictive of cessation activity . Warning size increases warning effectiveness and graphic warnings may be superior to text-based warnings . While there is partial wear-out in the initial impact associated with all warnings , stronger warnings tend to sustain their effects for longer . These findings support arguments for governments to exceed minimum FCTC requirements on warnings INTRODUCTION Cigarette packaging is among the most prominent forms of tobacco marketing . This study examined the impact of cigarette pack design among young women in the United States . METHOD A national sample of 18- to 19-year-old females in the United States completed an online survey in February 2010 . Participants were r and omized to view eight cigarette packs design ed according to one of four experimental conditions : fully br and ed female packs , same packs without descriptors ( e.g. , " slims " ) , same packs without br and imagery or descriptors ( " plain " packs ) , and br and ed non-female br and s. Participants rated packs on measures of appeal and health risk and completed a behavioral pack selection task . RESULTS Fully br and ed female packs were rated significantly more appealing than the same packs without descriptors , " plain " packs , and non-female-br and ed packs . Female-br and ed packs were associated with a greater number of positive attributes including glamour , slimness , and attractiveness and were more likely to be perceived as less harmful . Approximately 40 % of smokers and nonsmokers requested a pack at the end of the study ; female-br and ed packs were 3 times more likely to be selected than plain packs . CONCLUSION Plain packaging and removing descriptors such as " slims " from cigarette packs may reduce smoking susceptibility among young women CONTEXT There is no vali date d , theory-based tool for assessing the onset of nicotine dependence . However , the use of all addictive substances can result in a loss of autonomy . We propose that nicotine dependence begins when autonomy is lost , ie , when the sequelae of tobacco use , either physical or psychological , present a barrier to quitting . OBJECTIVES To test the autonomy theory of nicotine dependence , and to evaluate the Hooked on Nicotine Checklist ( HONC ) as a measure of the loss of autonomy over tobacco use . DESIGN The psychometric performance and concept validity of the HONC were evaluated in a 30-month prospect i ve longitudinal study of the natural history of tobacco use in a cohort of 679 seventh- grade students . RESULTS As hypothesized , endorsement of a single item on the HONC was associated with a failed attempt at smoking cessation ( odds ratio [ OR ] , 29 ; 95 % confidence interval [ CI ] , 13 - 65 ) , continued smoking until the end of follow-up ( OR , 44 ; 95 % CI , 17 - 114 ) , and daily smoking ( OR , 58 ; 95 % CI , 24 - 142 ) . Scores on the HONC correlated with the maximum amount smoked ( r = 0.65 ; P<.001 ) and the maximum frequency of smoking ( r = 0.79 ; P<.001 ) . Internal reliability was 0.94 . A 1-factor solution explained 66 % of the total variance . CONCLUSIONS The data support the autonomy theory that dependence begins with the loss of autonomy . The autonomy theory represents a potentially useful alternative to current concepts of nicotine dependence for adolescents , and the HONC appears to measure lost autonomy in adolescents . Construct validity was demonstrated by its utility in predicting failed cessation and the progression of tobacco use . In addition , the psychometric properties were excellent PURPOSE Cigarette packaging is the most prominent form of tobacco marketing remaining in countries such as the United Kingdom . The current study examined perceptions of cigarette packaging among female youth and the potential impact of " plain " cigarette packaging regulations . METHODS A national sample of 947 16- to 19-year-old female subjects in the United Kingdom completed an online survey . Participants were r and omized to view 10 cigarette packs design ed according to one of four experimental conditions : fully br and ed female packs , the same packs without descriptor words , the same packs without br and imagery or descriptors ( " plain " packs ) , and br and ed non-female br and s. Participants rated packs on measures of appeal and health risk , positive smoker image , and completed a behavioral pack selection task . RESULTS Plain packs were rated as the least appealing and worse tasting compared with all other conditions . Plain packs were also associated with fewer false beliefs about health risks compared with br and ed packs . Removing br and descriptors from packs significantly reduced measures of appeal and taste , particularly for br and s with flavor descriptors , such as cherry and vanilla . Plain packs were significantly less likely to Output:	Graphic health warnings were perceived as more effective than text-only warnings , with warnings depicting lung cancer , and oral diseases being perceived as particularly effective . Health warnings increased viewer fear , anxiety , shock , and guilt and were considered effective in preventing non-smokers from experimenting with tobacco and prompting current smokers to quit . Plain packaging reduced the attractiveness and other positive attributes of cigarette packaging , with darker colours found to be the most effective . When used in combination , plain packaging increased the visibility of graphic health warnings , with participants also perceiving them as having an increased tar content and having more serious health risks , and increased thoughts of quitting amongst smokers . Conclusions Graphic health warnings and plain packaging appear to increase adolescent awareness of the dangers of tobacco use .
MS21219	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: AIM : The seeds of the Nigella sativa plant have been used to promote health and fight disease for centuries , especially in the Middle East and in Southeast Asia . This plant has been a focus of much research . This clinical study was undertaken to know the adjuvant effect of N. sativa oil on various clinical and biochemical parameters of the insulin resistance syndrome . MATERIAL S AND METHODS : This prospect i ve study was conducted at a tertiary health care center in North India . After confirmation of diagnosis , 60 patients who fulfilled the inclusion and exclusion criteria were enrolled in this study . Written informed consent was taken from all the patients enrolled . Approval from the institutional ethical committee was also obtained . The patients were divided into two groups of 30 each . In group I ( the st and ard group ) , patients were advised tablet atorvastatin 10 mg once a day and tablet metformin 500 mg twice a day for a period of 6 weeks . In group II ( the N. sativa group ) , the patients were advised tablet atorvastatin 10 mg once a day , tablet metformin 500 mg twice a day , and N. sativa oil 2.5 ml twice daily for a period of 6 weeks . Fasting and postpr and ial blood glucose , fasting lipid profile , and waist circumference were recorded before therapy and after completion of therapy . RESULT : The treatment group showed significant ( P < 0.05 ) improvement with reference to total cholesterol , low density lipoprotein cholesterol ( LDL-C ) , and fasting blood glucose ( P < 0.05 ) . CONCLUSION : N. sativa oil was found to be effective as an add-on therapy in patients of insulin resistance syndrome . N. sativa oil has a significant activity in diabetic and dyslipidemic patients Abstract Objective : To determine the relation between exposure to glycaemia over time and the risk of macrovascular or microvascular complications in patients with type 2 diabetes . Design : Prospect i ve observational study . Setting : 23 hospital based clinics in Engl and , Scotl and , and Northern Irel and . Participants : 4585 white , Asian Indian , and Afro-Caribbean UKPDS patients , whether r and omised or not to treatment , were included in analyses of incidence ; of these , 3642 were included in analyses of relative risk . Outcome measures : Primary predefined aggregate clinical outcomes : any end point or deaths related to diabetes and all cause mortality . Secondary aggregate outcomes : myocardial infa rct ion , stroke , amputation ( including death from peripheral vascular disease ) , and microvascular disease ( predominantly retinal photo-coagulation ) . Single end points : non-fatal heart failure and cataract extraction . Risk reduction associated with a 1 % reduction in up date d mean HbA1c adjusted for possible confounders at diagnosis of diabetes . Results : The incidence of clinical complications was significantly associated with glycaemia . Each 1 % reduction in up date d mean HbA1c was associated with reductions in risk of 21 % for any end point related to diabetes ( 95 % confidence interval 17 % to 24 % , P<0.0001 ) , 21 % for deaths related to diabetes ( 15 % to 27 % , P<0.0001 ) , 14 % for myocardial infa rct ion ( 8 % to 21 % , P<0.0001 ) , and 37 % for microvascular complications ( 33 % to 41 % , P<0.0001 ) . No threshold of risk was observed for any end point . Conclusions : In patients with type 2 diabetes the risk of diabetic complications was strongly associated with previous hyperglycaemia . Any reduction in HbA1c is likely to reduce the risk of complications , with the lowest risk being in those with HbA1c values in the normal range ( < 6.0 % ) UNLABELLED Diabetes mellitus is a common chronic disease affecting millions of people world wide . St and ard treatment is failing to achieve required correction of blood glucose in many patients . Therefore , there is a need for investigating potential hypoglycemic drugs or herbs to improve glycemic control in diabetic patients . Nigella sativa seeds were used as an adjuvant therapy in patients with diabetes mellitus type 2 added to their anti-diabetic medications . A total of 94 patient were recruited and divided r and omly into three dose groups . Capsules containing Nigella sativa were administered orally in a dose of 1 , 2 and 3 gm/day for three months . The effect of Nigella sativa on the glycemic control was assessed through measurement of fasting blood glucose ( FBG ) , blood glucose level 2 hours postpr and ially ( 2 hPG ) , and glycosylated hemoglobin ( HbA1c ) . Serum C-peptide and changes in body weight were also measured . Insulin resistance and beta-cell function were calculated usin the homeostatic model assessment ( HOMA2 ) . Nigella sativa at a dose of 2 gm/day caused significant reductions in FBG , 2hPG , and HbA1 without significant change in body weight . Fasting blood glucose was reduced by an average of 45 , 62 and 56 mg/dl at 4 , 8 and 12 weeks respectively . HbAlC was reduced by 1.52 % at the end of the 12 weeks of treatment ( P<0.0001 ) . Insulin resistance calculated by HOMA2 was reduced significantly ( P<0.01 ) , while B-cell function was increased ( P<0.02 ) at 12 weeks of treatment . The use of Nigella sativa in a dose of 1 gm/day also showed trends in improvement in all the measured parameters but it was not statistically significant from the baseline . However , no further increment in the beneficial response was observed with the 3 gm/day dose . The three doses of Nigella sativa used in the study did not adversely affect either renal functions or hepatic functions of the diabetic patients throughout the study period . IN CONCLUSION the results of this study indicate that a dose of 2 gm/ day of Nigella sativa might be a beneficial adjuvant to oral hypoglycemic agents in type 2 diabetic patients Output:	Nigella sativa was shown to significantly improve laboratory parameters of hyperglycemia and diabetes control after treatment with a significant fall in fasting blood glucose , blood glucose level 2 h postpr and ial , glycated hemoglobin , and insulin resistance , and a rise in serum insulin . In conclusion , these findings suggested that Nigella sativa could be used as an adjuvant for oral antidiabetic drugs in diabetes control
MS21220	*TASK* the task is to summarize an input biomedical literature in six sentences *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 objective was to compare the effectiveness and safety of traditional Chinese moxibustion to that of sham moxibustion in patients with chronic knee osteoarthritis ( KOA ) pain . Methods We conducted a r and omized placebo-controlled trial involving 110 patients with KOA who met the inclusion criteria . These patients r and omly received either active moxibustion ( n = 55 ) or sham moxibustion control ( n = 55 ) at acupoints Dubi ( ST 35 ) , extra-point Neixiyan ( EX-LE 4 ) , and an Ashi ( tender ) point three times a week for 6 weeks . Effects were evaluated with Western Ontario and McMaster Universities ’ Osteoarthritis Index ( WOMAC VA 3.1 ) criteria at the end of the course of treatment and 3 , 12 , and 24 weeks after the initial treatment . Results The WOMAC pain scores showed greater improvement in the active treatment group than in control at weeks 3 ( P = 0.012 ) , 6 ( P < 0.001 ) , 12 ( P = 0.002 ) , and 24 ( P = 0.002 ) as did WOMAC physical function scores of the active treatment group at week 3 ( P = 0.002 ) , 6 ( P = 0.015 ) , and 12 ( P < 0.001 ) but not 24 ( P = 0.058 ) . Patients and practitioners were blinded successfully , and no significant adverse effects were found during the trial . Conclusions A 6-week course of moxibustion seems to relieve pain effectively and improve function in patients with KOA for up to 18 weeks after the end of treatment . Moxibustion treatment appears to be safe , and the usefulness of the novel moxa device was vali date d . Trial registration Current controlled trial : IS RCT N68475405 . Registered 4 April 2014 Objective . To observe the effects of traditional Chinese moxibustion , compared with sham moxibustion , on the quality of life ( QOL ) in patients with chronic knee osteoarthritis ( KOA ) . Methods . This is a r and omized double-blinded , placebo-controlled trial . 150 patients with KOA were r and omly allocated to either a true moxibustion treatment ( n = 77 ) or a sham moxibustion treatment ( n = 73 ) three times a week for six weeks . The QOL of patients was evaluated with SF-36 at baseline and 3 , 6 , and 12 weeks after baseline . Results . 136 patients were available for analysis . Participants in the true moxibustion group experienced statistically significantly greater improvement in GH ( general health ) scores than the sham group at week 6 ( P = 0.015 ) and week 12 ( P = 0.029 ) . Participants in the true moxibustion group experienced statistically significantly greater improvement in VT ( vitality ) scores than the sham group at week 12 ( P = 0.042 ) . No significant adverse effects were found during the trial . Conclusion . A 6-week moxibustion treatment seems to improve general health and vitality , which are associated with physical and mental quality of life , in patients with KOA up to 12 weeks , relative to credible sham moxibustion . This trial is registered with Clinical trials.gov IS RCT N68475405 Introduction This study tested the effectiveness of moxibustion on pain and function in chronic knee osteoarthritis ( KOA ) and evaluated safety . Methods A multi-centre , non-blinded , parallel-group , r and omised controlled trial compared moxibustion with usual care ( UC ) in KOA . 212 South Korean patients aged 40–70 were recruited from 2011–12 , stratified by mild ( Kellgren/Lawrence scale grade s 0/1 ) and moderate-severe KOA ( grade s 2/3/4 ) , and r and omly allocated to moxibustion or UC for four weeks . Moxibustion involved burning mugwort devices over acupuncture and Ashi points in affected knee(s ) . UC was allowed . Korean Western Ontario and McMaster Universities Question naire ( K-WOMAC ) , Short Form 36 Health Survey ( SF-36v2 ) , Beck Depression Inventory ( BDI ) , physical performance test , pain numeric rating scale ( NRS ) and adverse events were evaluated at 5 and 13 weeks . K-WOMAC global score at 5 weeks was the primary outcome . Results 102 patients ( 73 mild , 29 moderate-severe ) were allocated to moxibustion , 110 ( 77 mild , 33 moderate-severe ) to UC . K-WOMAC global score ( moxibustion 25.42+/−SD 19.26 , UC 33.60+/−17.91 , p<0.01 , effect size = 0.0477 ) , NRS ( moxibustion 44.77+/−22.73 , UC 56.23+/−17.71 , p<0.01 , effect size = 0.0073 ) and timed-st and test ( moxibustion 24.79+/−9.76 , UC 25.24+/−8.84 , p = 0.0486 , effect size = 0.0021 ) were improved by moxibustion at 5 weeks . The primary outcome improved for mild but not moderate-severe KOA . At 13 weeks , moxibustion significantly improved the K-WOMAC global score and NRS . Moxibustion improved SF-36 physical component summary ( p = 0.0299 ) , bodily pain ( p = 0.0003 ) , physical functioning ( p = 0.0025 ) and social functioning ( p = 0.0418 ) at 5 weeks , with no difference in mental component summary at 5 and 13 weeks . BDI showed no difference ( p = 0.34 ) at 5 weeks . After 1158 moxibustion treatments , 121 adverse events included first ( n = 6 ) and second degree ( n = 113 ) burns , pruritus and fatigue ( n = 2 ) . Conclusions Moxibustion may improve pain , function and quality of life in KOA patients , but adverse events are common . Limitations included no sham control or blinding . Trial Registration Clinical Research Information Service ( CRIS ) OBJECTIVE To observe the effect of Aconite cake-separated moxibustion on primary knee osteoarthritis of liver and kidney deficiency type . METHODS Fifty-six cases of such disease ( 80 knees ) were r and omly divided into a cake-separated moxibustion group ( 41 knees ) with Neixiyan ( EX-LE 5 ) , Dubi ( ST 35 ) , Yinlingquan ( SP 9 ) etc . selected , and a western medicine group ( 39 knees ) were treated with oral administration of Sodium Diclofenate Slow-released Tablet . RESULTS The cumulative score for symptoms and signs was ( 37.41 + /- 6.61 ) points before treatment and ( 9.37 + /- 8.15 ) points after treatment in the cake-separated moxibustion group and ( 37.64 - 6.00 ) points before treatment and ( 12.05 + /- 8.83 ) points after treatment in the western medicine group , with a very significant difference before and after treatment in the two groups ( P < 0.01 ) ; two months after treatment , it was ( 11.71 + /- 8.69 ) points in the cake-separated moxibustion group and ( 15.95 + /- 9.96 ) points in the western medicine group , the former being better than the latter ( P < 0.05 ) . After the end of treatment , there was no significant difference in the comprehensive therapeutic effect between the two groups ( P > 0.05 ) , the cured and markedly effective rate was 63.4 % in the cake-separated moxibustion group and 48.7 % in the western medicine group , but two months after treatment , the cured and markedly effective rate of 56.1 % in the cake-separated moxibustion group was better than 33.3 % in the western medicine group ( P < 0.05 ) . CONCLUSION Aconite cake-separated moxibustion has an ideal therapeutic effect on primary knee osteoarthritis of liver and kidney deficiency type , and the therapeutic effect at anaphase is better than that of Sodium Diclofenate Slow-released Tablet OBJECTIVE To investigate the role of adenosine tri-phosphate ( ATP ) purinergic signaling in mast cells ( MCs ) modulated by heat to further underst and the molecular mechanisms of moxibustion . METHODS Skin temperatures induced by monkshood cake moxibustion were evaluated by measuring the Neiguan acupoint ( PC 6 ) from 31 participants with a digital thermocouple thermometer . Temperatures of 43 ° C and 52 ° C were applied to cultured human leukemia mast cell line HMC-1 in vitro . Calcium fluorescence was applied to detect intracellular Ca2 + ( [ Ca2 + ] ) . Extracellular ATP contents were measured by luciferin-luciferase assay . RESULTS Maximum skin temperatures mostly ranged from 40 - 45 ° C , but some reached up to 50 ° C . Both 43 ° C and 52 ° C induced MC degranulation , which was accompanied by an increase in [ Ca2 + ] and ATP release . Complexing extracellular Ca2 + with 5 mM ethylene glycol-bis ( β-aminoethyl ether)-N , N , N',N'-tetraacetic acid ( EGTA ) inhibited the noxious , heat-induced elevation of [Ca2+]i and prevented the enhanced ATP secretion by those . cells at 52 ° C , but not 43 ° C . CONCLUSION Monkshood cake moxibustion can generate heat sufficient to trigger cellular events of MCs , including degranulation , [Ca2+]i elevation , and ATP release , suggesting that purinergic signals originating from MCs are possibly the initiating response of acupoints to moxibustion OBJECTIVE To evaluate the clinical efficacy of warm-needling moxibustion for knee osteoarthritis ( KOA ) , and to explore its effects on isokinetic strength of lower limb muscle . METHODS Fifty cases of KOA were r and omly divided into an observation group ( 25 cases ) and a control group ( 21 cases ) , but 4 cases lost contact . The observation group was treated with warm-needling moxibustion at Dubi ( ST 35 ) , Neixiyan ( EX-LE 4 ) , Xuehai ( SP 10 ) , Liangqiu ( ST 34 ) , Yinlingquan ( SP 9 ) , Yanglingquan ( GB 34 ) , Weizhong ( BL 40 ) , Heyang ( BL 55 ) and Fengshi ( GB 31 ) for 40 min per treatment . The first 6 treatments were given once a day , and the last 6 treatments were given once every other day . 12 treatments were taken as one course , and totally 3-week treatment was given . No treatment was given in the control group for 3 weeks . The isokinetic strength of extensor muscle and flexor muscle , including the total work , absolute peak torque ( aPT ) and relative peak torque ( rPT ) , and Western Ontario and McMaster Universities Arthritis Index ( WOMAC ) , and comprehensive efficacy were observed and compared in the two groups . RESULTS Compared before treatment , the total work , aPT and rPT of the extensor and flexor muscle increased significantly after treatment in the observation group ( P<0.01 , P<0.05 ) , but the flextion/extention ratio was lowered ( P<0.05 ) . In the control group , aPT and rPT of flexor muscle were reduced after treatment ( P<0.05 , P<0.01 ) . The total work , aPT and rPT of the extensor muscle in the observation group were higher than those in the control group after treatment ( P<0.05 , P<0.01 ) , but the flextion/extention ratio was lowered ( P<0.05 ) . The item score and total score of WOMAC were reduced in the observation group after treatment ( all P<0.01 ) , but no significant change was observed in the control group ( all P>0.05 ) . The pain score , stiffness scores and total score of WOMAC in the observation group were lower than those in the control group ( P<0.01 , P<0.05 ) ; the score of daily function activities was declined in the observation group , but not significantly different from that in the control group ( P>0.05 ) . The total effective rate was 88.0 % ( 22/25 ) in the observation group . CONCLUSIONS Warm-needling moxibustion could relieve pain , improve function and muscle balance , strengthen extensor and flexor muscle power , especially extensor , which has superior clinical efficacy OBJECTIVE To investigate hip or knee symptoms in older persons from a longitudinal , population perspective , and to determine the impact of persistent hip or knee pain on general health status over time . METHODS A postal question naire was sent to a r and om sample of 5,500 individuals Output:	Conclusion Moxibustion treatment for KOA is more effective than the positive control ( western medicine ) or negative control ( placebo moxibustion or no treatment or UC ) , and there were fewer adverse reactions to moxibustion .
MS21221	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background There is a burglar association between diabetes and periodontitis . Many studies has shown that periodontitis treatment can help improving glycemic control in diabetes patients but little evidence of non-surgical treatment benefit is available in sub Saharan african diabetes patients . We aim ed to assess the effects of non-surgical periodontal treatment ( NSPT ) of chronic periodontitis on glycaemic control in poorly controlled type 2 diabetes patients ( T2D ) in a sub-Saharan Africa urban setting . Methods A total of 34 poorly controlled T2D patients with chronic periodontitis aged 51.4 ± 8.8 years ( mean ± SD ) , with known duration of diabetes of 55.5 ± 42.6 months , and HbA1c of 9.3 ± 1.3 % were r and omly assigned to two groups . The treatment group ( Group 1 , n = 17 ) received immediate ultrasonic scaling , scaling and root planning along with subgingival 10 % povidone iodine irrigation , whereas the control group ( Group 2 , n = 17 ) was assigned to receive delayed periodontal treatment 3 months later . Pharmacological treatment was unchanged and all participants received the same st and ardized education session on diabetes management and dental hygiene . The primary outcome was the 3-month change in HbA1c from baseline . Plaque index ( PI ) , gingival bleeding index ( GBI ) , pocket depth ( PD ) , clinical attachment loss ( CAL ) were also assessed prior to , at 6 and 12 weeks after enrolment . Results Two subjects in each group were excluded from the study . Data were analyzed on thirty patients ( 15 per group ) . Non-surgical periodontal treatment with education for better dental hygiene ( group 1 ) significantly improved all periodontal parameters whereas education only ( group 2 ) improved only the plaque index among all periodontal parameters . Immediate non-surgical periodontal treatment induced a reduction of HbA1c levels by 3.0 ± 2.4 points from 9.7 ± 1.6 % at baseline to 6.7 ± 2.0 % 3 months after NSPT , ( p ˂ 0.001 ) but the change was not significant in group 2 , from mean 8.9 ± 0.9 % at baseline vs 8.1 ± 2.6 % after 3 months ( p = 0.24 ) . Conclusion Non-surgical periodontal treatment markedly improved glycaemic control with an attributable reduction of 2.2 points of HbA1c in poorly controlled T2D patients in a sub Saharan setting .Trial registration Clinical Trials.gov Identifier : NCT02745015 Date of registration : July 17 , 2016 ‘ Retrospectively registered ’ BACKGROUND Cytokine dysregulation plays an important role in Type 2 Diabetes Mellitus ( T2DM ) and Chronic Periodontitis ( CP ) with a commonality in pathogenic mechanisms . CP is considered the sixth complication of diabetes and may have an increased influence on systemic levels of cytokines in individuals with T2DM . OBJECTIVE This study investigated two pro- , and two presumed anti-inflammatory cytokines and their ratios in the serum of healthy individuals , in chronic periodontitis with and without T2DM with , and without CP and in CP alone aim ed at evaluating the systemic inflammatory burden of a local oral infection . METHODS Eighty participants were divided equally into four groups as healthy volunteers ( H ) and patients having T2DM with , and without CP ( T2DM+CP , and T2DM ) and only CP ( CP ) . Serum sample s were collected to measure glycated hemoglobin ( HbA1c ) , R and om Blood Sugar ( RBS ) and also Tumor Necrosis Factor (TNF)-α , Interleukin (IL)-4 , -6 - 10 were assessed using commercially available ELISA kits . RESULTS The cytokines were detected in all groups . Significant differences were observed between groups for all the clinical , biochemical parameters and cytokines . Cytokine levels and the ratios showed significant correlations . The ratios of the cytokines differed significantly amongst groups , were highest in T2DM+CP . CONCLUSION In this study , the cytokine ratios provided a qualitative profile along with the absolute levels in T2DM with periodontitis , indicative of an intensified systemic inflammatory state OBJECTIVE To evaluate the effectiveness of community periodontal care intervention in type 2 diabetic patients with chronic periodontitis who participated in community non-communicable diseases management service . METHODS The r and omized controlled and blinded community trial with a duration of six months was design ed to compare effects of " periodontal initial therapy " on group I(22 cases ) , of " professional mechanical tooth cleaning ( PMTC ) , i.e. coronal scaling " on group II(19 cases ) and of " non- clinical therapy " on the control group(25 cases ) . The clinical periodontal indexes , such as probing depth ( PD ) , attachment loss ( AL ) , modified bleeding index ( mBI ) , plaque index ( PLI ) were obtained with a Williams type periodontal probe ; Laboratory examinations including glycosylated haemoglobin A1(HbA1C ) , glucose assay , were conducted . RESULTS The reductions of PD in groups I and II were 0.71 and 0.70 mm , respectively , which was more significant than in control group ( 0.20 mm ) ; the reductions of AL in groups I , II , and control group were 0.86 , 0.57 , and 0.03 mm , respectively , which showed significance in all the three groups . The subjects of groups I and II had 0.56 % and 1.01 % reductions of HbA1C respectively , and the significance was observed in group II . In addition , the improvement of HbA1C values in group II was highly correlated with the decrease in gingivitis ( r=0.51 , P=0.03 ) . CONCLUSION The community periodontal care approaches implemented in the community health service centers have significantly improved periodontal health as well as reduced glycemic level , which could be regarded as basic health care strategies for the patients with diabetes AIM The aim of this r and omized controlled clinical trial was to evaluate the clinical effects of chlorhexidine ( CHX ) application in a full-mouth disinfection ( FMD ) protocol in poorly controlled type-2 diabetic subjects with generalized chronic periodontitis . MATERIAL AND METHODS Thirty-eight subjects were r and omly assigned into FMD group ( n=19 ) : full-mouth scaling and root planing ( FMSRP ) within 24 h + local application of CHX gel + CHX rinses for 60 days or Control group ( n = 19 ) : FMSRP within 24 h + local application of placebo gel + placebo rinses for 60 days . Clinical parameters , glycated haemoglobin and fasting plasma glucose were assessed at baseline , 3 , 6 and 12 months post-therapies . RESULTS All clinical parameters improved significantly at 3 , 6 and 12 months post-therapies for both groups ( p < 0.05 ) . There were no significant differences between groups for any clinical parameters , and glycemic condition at any time-point ( p > 0.05 ) . CONCLUSIONS The treatments did not differ with respect to clinical parameters , including the primary outcome variable ( i.e. changes in clinical attachment level in deep pockets ) , for up to 12 months post-treatments Background 40 subjects with type 2 diabetes and moderate to severe CP were r and omly distributed to groups receiving either NSPT or OHI . Periodontal parameters , glycosylated haemoglobin ( HbA1c ) and high-sensitivity C-reactive protein ( hs-CRP ) were evaluated at baseline , 2- and 3-months intervals . Methods 40 subjects with type 2 diabetes and moderate to severe CP were r and omly distributed to groups receiving either NSPT or OHI . Periodontal parameters , glycosylated haemoglobin ( HbA1c ) and high-sensitivity C-reactive protein ( hs-CRP ) were evaluated at baseline , 2- and 3-months intervals . Results 15 subjects from NSPT group and 17 from OHI group completed the study . The difference in plaque index ( PI ) between NSPT and OHI groups were significant at 2 months recall ( p = 0.013 ) . There was no significant difference between NSPT and OHI group for all other clinical periodontal parameters , HbA1c and CRP levels . At 3 months post-therapy , periodontal parameters improved significantly in both groups with sites with probing pocket depth ( PPD ) < 4 mm reported as 98 ± 1.8 % in NSPT group and 92 ± 14.9 % in OHI group . Mean PPD and mean probing attachment loss ( PAL ) within the NSPT group reduced significantly from baseline ( 2.56 ± 0.57 mm , 3.35 ± 0.83 mm ) to final visit ( 1.94 ± 0.26 mm , 2.92 ± 0.72 mm ) ( p = 0.003 , p < 0.001 ) . For OHI group , improvements in mean PPD and mean PAL were also seen from baseline ( 2.29 ± 0.69 mm , 2.79 ± 0.96 mm ) to final visit ( 2.09 ± 0.72 mm , 2.62 ± 0.97 mm ) ( p < 0.001 for both ) . Similarly , HbA1c levels decreased in both groups with NSPT group recording statistically significant reduction ( p = 0.038 ) . Participants who demonstrated ≥ 50 % reduction in PPD showed significant reductions of HbA1c and hs-CRP levels ( p = 0.004 and p = 0.012 ) . Conclusion NSPT significantly reduced PI at 2 months post-therapy as compared to OHI . Both NSPT and OHI demonstrated improvements in other clinical parameters as well as HbA1c and CRP levels . Trial registration Clinical Trials.gov : NCT01951547 BACKGROUND AND OBJECTIVE Several studies have shown that periodontitis can complicate the severity of diabetes by worsening the degree of glycemic control . The purpose of this study was to determine the effect of full-mouth tooth extraction on glycemic control among type 2 diabetic patients . MATERIAL AND METHODS A total of 58 patients with type 2 diabetes mellitus and advanced periodontitis who were requiring extraction of all remaining teeth were r and omized consecutively into treatment ( full-mouth tooth extraction ) and control groups ( no treatment ) . Eight patients were lost to follow-up or reported use of antibiotics , leaving 50 patients to be included in the analysis . All patients had all their remaining teeth in a hopeless condition . Relevant data were collected , and glycosylated hemoglobin ( HbA(1c ) ) and fasting blood glucose levels were measured at baseline and at follow-up times of 3 and 6 mo . RESULTS At baseline , the mean ( SD ) HbA(1c ) level was 8.6 % ( 1.24 ) in the treatment group and 7.7 % ( 0.87 ) in the control group . In the treatment group , the mean HbA(1c ) level decreased significantly from 8.6 % at baseline to 7.4 % after 3 mo of denture treatment , and continued to decrease to 7.3 % after 6 mo . In the control group , the mean HbA(1c ) decreased from 7.7 % at baseline to 7.5 % after 3 mo , and remained almost the same after 6 mo . After adjusting for the baseline HbA(1c ) , the mean reduction in HbA(1c ) after 3 mo in the treatment group [ 1.23 % ( 0.79 ) ] was significantly higher than the mean reduction in the control group [ 0.28 % ( 0.87 ) ] . CONCLUSION Full-mouth tooth extraction result ed in an improvement in glycemic control among diabetic patients . Large-scale multicentre clinical trials are needed to confirm the current evidence Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more OBJECTIVES Patients with diabetes have a poor oral health-related quality of life ( OHRQoL ) . It is not clear if this situation could be changed with effective periodontal treatment . This study examined both patients with diabetes and systemically healthy individuals to discover the impact of a gingivitis treatment protocol on OHRQoL and its relation to objective periodontal parameters . DESIGN After ultrasonic debridement , patients were r and omly assigned to an essential-oils ( EO ) or placebo mouthwash group . At baseline and 3 months , OHRQoL was assessed with the Oral Health and Quality of Life-United Kingdom question naire ( OHQoL-UK ) along with clinical , halitometric , microbiological and inflammatory objective parameters . The primary outcome was a change in OHQoL-UK scores . A factor analysis was performed and the impact of the extracted quality of life factor ( QLF ) and its interactions with diabetes , treatment , and time on the objective parameters , were tested by multiple linear regression models ( p < 0.05 ) . Chi-Square test compared question naire-answering profiles ( p<0.05 ) . RESULTS Combined treatment with EO provided OHQoL improvements in both systemic conditions . Positive effect Output:	CONCLUSIONS SRP has an impact on metabolic control and reduction of systemic inflammation of patients with T2D
MS21222	*TASK* the task is to summarize an input biomedical literature in six sentences *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 daily dose of aspirin in desensitization in aspirin‐sensitive asthmatics with nasal polyps is still a matter of debate INTRODUCTION Nasal polyposis associated with aspirin-intolerant asthma tends to be difficult to control , with frequent recurrences . We examined the effect of intranasal lysine-aspirin administration on resistant nasal polyps of asthmatic , aspirin-intolerant patients , when used in addition to routine therapy . PATIENTS AND METHODS Thirteen patients with asthma and intolerance to aspirin were recruited . All but one had undergone numerous polypectomies and were uncontrolled on st and ard therapy with intranasal corticosteroids , leukotriene receptor antagonists and nasal douching . Aspirin treatment involved one drop ( 100 microl ) of 30 mg/ml lysine-aspirin solution to each nostril , initially daily , increased every two or three days up to a maximal of 18 drops ( 54 mg lysine-aspirin ) a day . Nasal symptoms , nitric oxide level , nasal inspiratory peak flow rate , peak expiratory flow rate and nasendoscopic grading were assessed prior to therapy and three months later . We also compared the change in endoscopic polyp scores during three months of lysine-aspirin administration with the changes which had occurred during the three months prior to administration ( during which time other therapies had been identical ) . RESULTS Nasal blockage symptoms tended to decrease ; other nasal symptoms were unchanged . Significant changes were seen in nasal inspiratory peak flow rate ( 103.3 + /- 18.9 and 140.0 + /- 16.7 l/min before and after aspirin , respectively ; p = 0.014 ) , but not in peak expiratory flow rate ( 438.7 + /- 33.4 and 440.0 + /- 28.4 l/min before and after aspirin , respectively ; p = 0.700 ) . Nasal nitric oxide levels rose significantly ( in both sides , p = 0.028 ) . Expired chest nitric oxide levels did not change . Nasal polyp scores on nasendoscopic examination were significantly reduced ( right side , p = 0.027 ; left side , p = 0.018 ) . Compared with the preceding three months , adding intranasal lysine-aspirin application had the effect on decreasing nasal polyp volume ( right side , p = 0.031 ; left side , p = 0.016 ) . CONCLUSION This open study suggests that intranasal lysine-aspirin administration reduces nasal polyp volume in aspirin-intolerant patients , without any adverse affect on concomitant asthma . This was a preliminary study and should be followed by a placebo-controlled , double-blind trial BACKGROUND Patients with aspirin-sensitive rhinosinusitis , which is frequently associated with intrinsic bronchial asthma , can be desensitized by long-term treatment with oral aspirin . The exact mechanisms of this desensitization remain obscure , but modulations of the eicosanoid pathway occur and can be monitored with the help of a practicable in vitro assay on mixed leukocyte cultures . OBJECTIVE To monitor the effect of low-dose aspirin desensitization therapy , 100 mg/d , objective ly by an in vitro assay . DESIGN In a prospect i ve study , 30 patients with aspirin intolerance , who were treated following a desensitization protocol with a dose of oral aspirin of only 100 mg/d were followed up for 1 year and reassessed every 3 months clinical ly and in vitro . RESULTS Twenty-five patients showed a normalization of in vitro eicosanoid levels during this period , 4 showed some improvement , and 1 showed no therapeutic effect on eicosanoid release . Clinical follow-up revealed a low recurrence rate of nasal polyposis , with recurrent disease only in 4 individuals who also showed no normalization of eicosanoid release levels . Furthermore , a reduction of the average incidence of purulent episodes of sinusitis was seen after 1 year . Of 12 patients with asthma , 9 experienced marked improvement in pulmonary function . Of 16 individuals with a marked impairment of nasal breathing , 14 felt an increase of nasal patency , and 7 of 11 patients with pretreatment hyposmia had an improved sense of smell after 1 year . CONCLUSIONS Desensitization therapy in patients with aspirin-sensitive rhinosinusitis can be successfully performed with low oral doses of aspirin , and the individual course throughout the desensitization can be monitored with the help of an in vitro analysis of eicosanoid release from mixed leukocyte cultures OBJECTIVES /HYPOTHESIS Evidence is lacking to guide the postoperative management of Samter 's triad patients with chronic rhinosinusitis with polyposis ( CRSwP ) undergoing endoscopic sinus surgery ( ESS ) . The purpose of this study was to compare three different st and ardized medication regimens prescribed to these patients after ESS . STUDY DESIGN Three-arm , r and omized , double-blinded , controlled trial . METHODS Patients with Samter 's triad undergoing ESS were postoperatively r and omized into three medication regimens , those being saline irrigation alone ( control group A ) , saline irrigation plus separate budesonide nasal spray ( group B ) , and saline irrigation mixed with budesonide nasal spray ( group C ) . Outcome measures were Sino-Nasal Outcome Test scores , Lund-Mackay computed tomography scores , and Lund-Kennedy endoscopic scores taken at preoperative baseline , and then at 6 months and 1 year postoperatively . Side effect profiles were also measured ( adrenocorticotropic hormone blood level ranges and intraocular pressure at the same interval points ) . Analysis of variance and χ(2 ) analyses were conducted using a Bonferroni correction method and routine descriptive statistics . Inter- and intragroup comparisons were made . RESULTS Sixty subjects were recruited . All groups were equivalent at baseline in all outcomes . All intragroup analyses showed statistically and clinical ly significant improvement in disease status as compared to baseline ( P < .0167 ) , with a sustained but lessened improvement at 1 year . However , no statistically or clinical ly significant differences were observed between groups at any time point ( P > .05 ) . There was no treatment effect noted . CONCLUSIONS In this study , nasal steroids did not confer any additional benefit over saline alone as post-ESS care for the Samter 's triad CRSwP patient population OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity BACKGROUND Aspirin desensitization followed by daily aspirin therapy is effective add-on treatment for patients with aspirin-exacerbated respiratory disease . Prior studies used 650 mg of aspirin twice daily , but studies at lower dosages were inconclusive . OBJECTIVE We sought to determine the optimal daily dosage of aspirin treatment . METHODS We studied 137 patients who had undergone successful aspirin desensitization and r and omized them into 2 groups , 650 mg twice daily versus 325 mg twice daily . After 1 month , patients either increased or decreased their dosage based on their symptom control and continued that dosage for the remainder of the year . RESULTS Patients taking either 650 mg twice daily or 325 mg twice daily showed significant improvements in number of sinus infections , sinus operations , and hospitalizations for asthma ( all P < .0001 ) . Anosmia , nasal/sinus symptoms , and asthma symptoms also improved in both groups ( all P < .03 ) . Systemic corticosteroid dosages decreased by 3- and 4-fold in the 325 mg twice daily and 650 mg twice daily groups , respectively . Of the 137 patients , 32 had adverse effects from or discontinued aspirin therapy : 14 ( 44 % ) of 32 from the group r and omized to taking 650 mg twice daily and 18 ( 56 % ) of 32 from the group r and omized to 325 mg twice daily . The most common adverse effect was dyspepsia . CONCLUSION Both dosages were efficacious , and side effects occurred in both groups at similar frequencies . Some patients initially taking 325 mg twice daily required an increase to 650 mg twice daily for optimal symptom control . CLINICAL IMPLICATION S We recommend that patients begin daily aspirin therapy with 650 mg twice daily and subsequently decrease to the lowest effective dosage ( usually 325 mg twice daily ) BACKGROUND Aspirin (ASA)-exacerbated respiratory disease ( AERD ) is characterized by aggressive inflammation of the respiratory tract and often requires topical and /or systemic corticosteroids to maintain partial control of this disease . Previous studies have revealed that ASA desensitization and subsequent treatment with ASA is associated with clinical improvement in AERD . OBJECTIVE The aim of the present study was to determine the effect of daily ASA treatment for the first 4 weeks after ASA desensitization . METHODS Thirty-eight patients underwent ASA oral challenge followed by ASA desensitization and daily ASA therapy . Changes in nasal and asthma symptoms , combined with changes in oral prednisone , were recorded daily during 4 weeks before and after desensitization . Severity of symptoms ranged from a scale of 1 to 5 ( 1 = asymptomatic and 5 = most severe symptoms ) . For statistical analyses the sum of nasal symptoms and asthma symptoms was calculated . Olfactory scores were also analyzed . RESULTS Nasal and asthma symptom scores , as well as olfactory scores , improved significantly ( P < 0.0001 ) . For the 15 patients taking prednisone , their mean doses decreased from 10.7 to 5.9 mg daily ( P = 0.0003 ) . CONCLUSIONS Our study suggests that ASA desensitization treatment is effective during the first 4 weeks of daily treatment with ASA Nasal polyposis is a multifactorial disease with a complex and still not completely understood pathogenesis . In more than one third of cases it is associated with intolerance to acetylsalicylic acid ( aspirin , ASA ) or to other non-steroidal anti-inflammatory drugs (NSAIDs).1 In as many as 20 % of cases nasal polyposis is also associated with the presence of bronchial asthma and /or rhinitis , configuring the so-called ASA triad or aspirin disease.2 Nasal polyps may benefit from medical treatment ( corticosteroids ) and surgery,3 but they frequently relapse soon after surgery4 - 9 with significant morbidity and high social and medical costs . Unfortunately , the effect of treatment with steroids is also often temporary.3 10 - 16 In the last two decades it has been observed that , in aspirin sensitive patients , oral aspirin desensitisation ( followed by long term aspirin treatment ) often results in an improvement in the clinical course of nasal polyposis.17 - 21 We have shown that aspirin sensitive patients with nasal polyposis have a higher rate of positive nasal provocation tests ( rhinomanometric measure of nasal airflow reduction after exposure to the drug ) with lysine-acetylsalicylate ( LAS ) than aspirin sensitive patients without nasal polyps.22 - 24 Moreover , LAS has been found to have an in vitro non-specific antiproliferative , dose dependent effect on the growth of fib Output:	Overall , most studies reported a significant improvement in symptom scores , decrease in corticosteroid use , and decrease in revision surgery . Unlike traditional treatments for nasal polyposis , aspirin desensitization targets AERD etiology rather than phenotype and can be an effective therapeutic option .
MS21223	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: A r and omised trial in breast cancer patients was design ed to compare the number of peripheral blood progenitor cells collected after mobilisation with a single dose of 10 microg/kg/day granulocyte colony-stimulating factor ( G-CSF ) ( n=14 ) or a split dose of 5 microg/kg twice daily ( n=14 ) . Both groups were well balanced . No significant differences were observed between groups regarding aphereses parameters . The total number of CD34 + cells collected was higher in the split-dose group ( mean of 7.1 and median of 7.4 x 10(6)/kg ) than in the single-dose group ( 5.6 and 5.8 x 10(6)/kg , respectively ) ( P=0.26 ) . The mean of CD34 + cells collected after the first apheresis procedure was 3.9 x 10(6)/kg for the split dose group and 3.1 x 10(6)/kg for the single-dose group ( P=0.24 ) . Circulating CD34 + cells before the first apheresis were higher for the split-dose group ( mean 79.7 vs 59.2 x 10(6)/l ) ( P=0.14 ) . All bone pain scores applied were significantly higher for the split-dose group . Our primary end point of improving the mean of total CD34 + cells collected to 2.5 x 10(6)/kg was not achieved with twice-daily G-CSF administration . Further studies evaluating different mobilisation schedules with G-CSF are needed to determine the optimal regimen AIM To evaluate in a multicentre r and omised study the effect on duration of febrile neutropenia ( FN ) , the safety and cost-effectiveness of a single subcutaneous pegfilgrastim injection compared with daily injections of filgrastim after peripheral blood stem cell transplantation in patients receiving high dose chemotherapy for myeloma and lymphoma . METHODS Patients were r and omly assigned to a single dose of pegfilgrastim at day 5 ( D5 ) or daily filgrastim from D5 to the recovery of absolute neutrophil count ( ANC ) to 0.5 G/L. Duration of FN , of neutrophil and platelet recovery , transfusion and antibiotic requirements were the main end-points of the study . Costs were calculated from D0 until transplant unit discharge . The incremental cost-effectiveness ratio was expressed as the cost per day of FN prevented . Probabilistic sensitivity analysis was performed by non-parametric bootstrap methods . RESULTS Between October 2008 and September 2009 , 10 centres enrolled 151 patients : 80 patients with lymphoma and 71 patients with myeloma . The mean duration of FN was 3.07 days ( st and ard deviation ( SD ) 1.96 ) in the pegfilgrastin arm and 3.29 ( SD 2.54 ) in the filgrastim one . Mean total costs were 23,256 and 25,448 euros for pegfilgrastim and filgrastim patients , respectively . There was a 62 % probability that pegfilgrastim strictly dominates filgrastim . CONCLUDING STATEMENT Pegfilgrastim after PBSC transplantation in myeloma and lymphoma is safe , effective when compared with filgrastim and could represent a cost-effective alternative in this setting Purpose : To compare the effectiveness , tolerance , and pharmacokinetics of a single dose of pegfilgrastim to daily filgrastim in children and young adults with sarcomas treated with dose-intensive combination chemotherapy . Experimental Design : Patients were r and omized to receive a single dose of 100 mcg/kg of pegfilgrastim s.c . or 5 mcg/kg/day of filgrastim s.c . , daily until neutrophil recovery after two treatment cycles with vincristine , doxorubicin , and cyclophosphamide ( VDC ) and two cycles of etoposide and ifosfamide ( IE ) . The duration of severe neutropenia ( absolute neutrophil count , ≤500/mcL ) during cycles 1 to 4 and cycle duration for all cycles were compared . Pharmacokinetics of pegfilgrastim and filgrastim and CD34 + stem cell mobilization were studied on cycle 1 . Growth factor – related toxicity , transfusions , and episodes of fever and neutropenia and infections were collected for cycles 1 to 4 . Results : Thirty-four patients ( median age , 20 years ; range 3.8 - 25.8 ) were enrolled , and 32 completed cycles 1 to 4 . The median ( range ) duration of absolute neutrophil count of < 500/mcL was 5.5 ( 3 - 8 ) days for pegfilgrastim and 6 ( 0 - 9 ) days for filgrastim ( P = 0.76 ) after VDC , and 1.5 ( 0 - 4 ) days for pegfilgrastim and 3.75 ( 0 - 6.5 ) days for filgrastim ( P = 0.11 ) after IE . More episodes of febrile neutropenia and documented infections occurred on the filgrastim arm . Serum pegfilgrastim concentrations were highly variable . Pegfilgrastim apparent clearance ( 11 mL/h/kg ) was similar to that reported in adults . Conclusion : A single dose per cycle of pegfilgrastim was well tolerated and may be as effective as daily filgrastim based on the duration of severe neutropenia and number of episodes of febrile neutropenia and documented infections after dose-intensive treatment with VDC and IE . ( Clin Cancer Res 2009;15(23):7361–7 Patients with lymphoproliferative disorders , c and i date to autologous stem cell transplantation ( ASCT ) , require mobilization with chemotherapy and granulocyte colony -stimulating factor ( G-CSF ) . This study looked for differences in hematopoietic peripheral stem cells ( HPSCs ) mobilization in response to the three available G-CSFs , namely lenograstim , filgrastim , and pegfilgrastim . Between 2000 and 2012 , 146 patients ( 66 M and 80 F ) who underwent ASCT for multiple myeloma , non-Hodgkin ’s lymphoma or Hodgkin ’s lymphoma were studied . All patients received induction therapy and then a mobilization regimen with cyclophosphamide plus lenograstim , or filgrastim , or pegfilgrastim . From days 12 to 14 , HPSCs were collected by two to three daily leukaphereses . Our results show that high-dose cyclophosphamide plus lenograstim achieved adequate mobilization and the collection target more quickly and with fewer leukaphereses as compared to filgrastim and pegfilgrastim . No differences between the three regimens were observed regarding toxicity and days to WBC and platelet recovery . Thus , lenograstim may represent the ideal G-CSF for PBSC mobilization in patients with lymphoproliferative diseases . Further studies are needed to confirm these results and better underst and the biological bases of these differences Ro 25‐8315 is produced by conjugation of rhG‐CSF mutant with polyethylene glycol ( PEG ) . The purpose of this study was to examine the pharmacodynamics and pharmacokinetics of Ro 25‐8315 in comparison with Filgrastim ( rhG‐CSF ) . Subjects received single subcutaneous doses of Ro 25‐8315 ranging from 10 to 150 μg/kg using a double‐blind , r and omized , placebo‐controlled design . Filgrastim was administered as a single dose ( 5 or 10 μg/kg ) and , following a 14‐day washout period , daily for 7 days . Ro 25‐8315 increased absolute neutrophil count ( ANC ) by 6‐ to 8‐fold and CD34 + cell count more than 30‐fold at the highest doses tested . Single doses ( 60–150 μg/kg ) of Ro 25‐8315 and multiple doses of Filgrastim had similar effects on ANC and CD34 + , although Ro 25‐8315 had a greater effect on CFU‐GM . The pharmacokinetics of Ro 25‐8315 were dose‐dependent , with peak concentrations and area under the serum concentration – time curve ( AUC ) increasing 100‐fold over the range of doses studied . Time to reach peak concentration ( Tmax ) and half‐life of Ro 25‐8315 averaged 20–30 hr at all doses , approximately three times longer than with Filgrastim . Adverse events were not serious and occurred with similar frequency with both products . Pegylation of rhG‐CSF mutant results in more desirable pharmacokinetic properties and a longer duration of action with effective increases in ANC and measures of peripheral blood progenitor cell mobilization for at least 1 week . Am . J. Hematol . 66:245–251 , 2001 . © 2001 Wiley‐Liss , Goals of workRecently , 6 cycles of R-CHOP-14 have been recommended as the reference st and ard regimen for the treatment of elderly patients with diffuse large B-cell lymphoma ( DLBCL ) . Pegfilgrastim has been shown to facilitate dose-dense chemotherapy schedules with a single administration per chemotherapy cycle . The aims of this study were to evaluate the use of pegfilgrastim in combination with the R-CHOP-14 regimen in a homogenous group of previously untreated elderly patients with DLBCL and to assess the pharmacokinetics of pegfilgrastim within this patient population . Material s and methods Ten patients with DLBCL between 60 and 80 years of age received a single subcutaneous injection of 6 mg pegfilgrastim 24 h after administration of R-CHOP chemoimmunotherapy , which was repeated for 6 to 8 cycles in two-weekly intervals . A total of 348 blood sample s were collected . Pegfilgrastim plasma levels and absolute neutrophil counts were measured every other day during the first treatment cycle and twice weekly during all consecutive cycles . Main results Sixty-three of 72 cycles ( 87.5 % ) could be delivered on time and at the planned dose . Median absolute neutrophil nadir was 0.32 g/l on day 9 . Grade 3/4 granulocytopenia occurred in all patients . Febrile neutropenia occurred in two patients . Plasma levels of pegfilgrastim remained elevated during the neutropenic phase . At the start of hematologic recovery , plasma concentrations of pegfilgrastim decreased rapidly to baseline levels . Median pegfilgrastim trough plasma level was 0.43 ng/ml on the day preceding the next application . Conclusions A single fixed dose of 6 mg of pegfilgrastim given once per cycle of R-CHOP-14 is effective in supporting neutrophil recovery to allow two-weekly drug administration in previously untreated elderly patients with DLBCL . However , close monitoring for infectious complications is m and atory in this patient population BACKGROUND It is not known whether increasing the dose of filgrastim after mobilizing chemotherapy improves collection of peripheral blood progenitor cells ( PBPC ) and leads to faster hematopoietic engraftment after autologous transplantation . STUDY DESIGN AND METHODS A r and omized , open-label , multicenter trial was carried out in patients with breast cancer , multiple myeloma , and lymphoma , in which patients were r and omized to receive 5 or 10 microg per kg per day of filgrastim after st and ard chemotherapy to mobilize PBPCs . After high-dose chemotherapy , the components from the first two leukapheresis procedures were returned , and all patients received 5 microg per kg day of filgrastim after transplantation . RESULTS A total of 131 patients were r and omized , of whom 128 were mobilized ( Group A , 5 microg/kg , n = 66 ; Group B , 10 microg/kg , n = 62 ) and 112 were transplanted . Only six patients were not transplanted because of insufficient CD34 + cell numbers . The median number of CD34 + cells collected in the first two leukapheresis procedures tended to be higher in Group B than in Group A ( 12.0 vs. 7.2 x 10(6)/kg , NS ) , but after transplantation there was no significant difference in median times to platelet ( 9 days in both groups ) or neutrophil ( 8 days in both groups ) engraftment or the number of platelet transfusions ( three in both groups ) . A subsequent subgroup analysis separating patients transplanted after first- or second-line chemotherapy also showed no measurable impact of filgrastim dose on the median CD34 + cell yield or on platelet engraftment in either subgroup . CONCLUSION PBPC mobilization with chemotherapy and 5 microg per kg of filgrastim is very efficient , and 10 microg per kg of filgrastim does not provide additional clinical benefit Summary . To date , no r and omized study has compared different doses of recombinant human granulocyte colony‐stimulating factor ( rhG‐CSF ) following submyeloablative mobilization chemotherapy . Therefore , we evaluated the effect of different doses of rhG‐CSF following mobilization chemotherapy on yields of CD34 + peripheral blood stem cells ( PBSC ) . Fifty patients were r and omized to receive 8 ( n = 25 ) versus 16 µg/kg/d ( Output:	No difference found on the quantity of CD34 + cells collected , number of apheresis procedure in successful mobilization , level of peak PB CD34 + cells achieved , and day of neutrophil and platelet engraftment
MS21224	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Abstract Objective : To evaluate the use of a computerised support system for decision making for implementing evidence based clinical guidelines for the management of asthma and angina in adults in primary care . Design : A before and after pragmatic cluster r and omised controlled trial utilising a two by two incomplete block design . Setting : 60 general practice s in north east Engl and . Participants : General practitioners and practice nurses in the study practice s and their patients aged 18 or over with angina or asthma . Main outcome measures : Adherence to the guidelines , based on review of case notes and patient reported generic and condition specific outcome measures . Results : The computerised decision support system had no significant effect on consultation rates , process of care measures ( including prescribing ) , or any patient reported outcomes for either condition . Levels of use of the software were low . Conclusions : No effect was found of computerised evidence based guidelines on the management of asthma or angina in adults in primary care . This was probably due to low levels of use of the software , despite the system being optimised as far as was technically possible . Even if the technical problems of producing a system that fully supports the management of chronic disease were solved , there remains the challenge of integrating the systems into clinical encounters where busy practitioners manage patients with complex , multiple conditions 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 AIM To compare the degree of asthma control in 2001 and 2005 in a primary care setting in Sweden . METHOD Two similar question naire surveys were performed in 2001 and 2005 with 1,012 and 224 asthma patients aged 18 - 45 r and omly selected from 42 and 56 primary health care centres , respectively . A classification of asthma control similar to the GINA guidelines was made using information obtained from the question naire . RESULTS In 2001 , 36.6 % had achieved asthma control , 23.8 % were partly controlled and 39.6 % uncontrolled . In 2005 , the corresponding figures were 40.2 % , 26.8 % and 33.0 % , respectively , with no difference between the two surveys ( p=0.114 ) . Uncontrolled asthma was more common in women ( p<0.001 in the first and p<0.05 in the second survey ) and smokers ( p<0.01 in the first and p<0.01 in the second survey ) . The use of combination corticosteroid/long-acting bronchodilator inhalers had increased - 34.2 % and 48.2 % , respectively ( p<0.001 ) - and many patients used their inhaled corticosteroids periodically . CONCLUSION In spite of treatment guidelines many patients in Swedish primary care still have insufficient asthma control Objective To determine whether mobile phone based monitoring improves asthma control compared with st and ard paper based monitoring strategies . Design Multicentre r and omised controlled trial with cost effectiveness analysis . Setting UK primary care . Participants 288 adolescents and adults with poorly controlled asthma ( asthma control question naire ( ACQ ) score ≥1.5 ) from 32 practice s. Intervention Participants were central ly r and omised to twice daily recording and mobile phone based transmission of symptoms , drug use , and peak flow with immediate feedback prompting action according to an agreed plan or paper based monitoring . Main outcome measures Changes in scores on asthma control question naire and self efficacy ( knowledge , attitude , and self efficacy asthma question naire ( KASE-AQ ) ) at six months after r and omisation . Assessment of outcomes was blinded . Analysis was on an intention to treat basis . Results There was no significant difference in the change in asthma control or self efficacy between the two groups ( ACQ : mean change 0.75 in mobile group v 0.73 in paper group , mean difference in change −0.02 ( 95 % confidence interval −0.23 to 0.19 ) ; KASE-AQ score : mean change −4.4 v −2.4 , mean difference 2.0 ( −0.3 to 4.2 ) ) . The numbers of patients who had acute exacerbations , steroid courses , and unscheduled consultations were similar in both groups , with similar healthcare costs . Overall , the mobile phone service was more expensive because of the expenses of telemonitoring . Conclusions Mobile technology does not improve asthma control or increase self efficacy compared with paper based monitoring when both groups received clinical care to guidelines st and ards . The mobile technology was not cost effective . Trial registration Clinical Trials NCT00512837 OBJECTIVE Computer-based clinical decision support systems ( CDSSs ) vary greatly in design and function . Using a taxonomy that we had previously developed , we describe the characteristics of CDSSs reported in the literature . METHODS We search ed PubMed and the Cochrane Library for r and omized controlled trials ( RCTs ) published in English between 1998 and 2003 that evaluated CDSSs . We coded each CDSS using our taxonomy . RESULTS 58 studies met our inclusion criteria . The 74 reported CDSSs varied greatly in context of use , knowledge and data sources , nature of decision support offered , information delivery , and workflow impact . Two distinct subsets of CDSSs were seen : patient-directed systems that provided decision support for preventive care or health-related behaviors via mail or phone ( 38 % of systems ) , and inpatient systems targeting clinicians with online decision support and direct online execution of the recommendations ( 18 % ) . 84 % of the CDSSs required extra staffing for h and ling CDSS-related input or output . CONCLUSION Reported CDSSs are heterogeneous along many dimensions . Caution should be taken in generalizing the results of CDSS RCTs to different clinical or workflow setting Background Computerized clinical decision support systems are information technology-based systems design ed to improve clinical decision-making . As with any healthcare intervention with cl aims to improve process of care or patient outcomes , decision support systems should be rigorously evaluated before widespread dissemination into clinical practice . Engaging healthcare providers and managers in the review process may facilitate knowledge translation and uptake . The objective of this research was to form a partnership of healthcare providers , managers , and research ers to review r and omized controlled trials assessing the effects of computerized decision support for six clinical application areas : primary preventive care , therapeutic drug monitoring and dosing , drug prescribing , chronic disease management , diagnostic test ordering and interpretation , and acute care management ; and to identify study characteristics that predict benefit . Methods The review was undertaken by the Health Information Research Unit , McMaster University , in partnership with Hamilton Health Sciences , the Hamilton , Niagara , Haldim and , and Brant Local Health Integration Network , and pertinent healthcare service teams . Following agreement on information needs and interests with decision-makers , our earlier systematic review was up date d by search ing Medline , EMBASE , EBM Review data bases , and Inspec , and review ing reference lists through 6 January 2010 . Data extraction items were exp and ed according to input from decision-makers . Authors of primary studies were contacted to confirm data and to provide additional information . Eligible trials were organized according to clinical area of application . We included r and omized controlled trials that evaluated the effect on practitioner performance or patient outcomes of patient care provided with a computerized clinical decision support system compared with patient care without such a system . Results Data will be summarized using descriptive summary measures , including proportions for categorical variables and means for continuous variables . Univariable and multivariable logistic regression models will be used to investigate associations between outcomes of interest and study specific covariates . When reporting results from individual studies , we will cite the measures of association and p-values reported in the studies . If appropriate for groups of studies with similar features , we will conduct meta-analyses . Conclusion A decision-maker- research er partnership provides a model for systematic review s that may foster knowledge translation and uptake OBJECTIVE We developed AsthmaCritic , a non-inquisitive critiquing system integrated with the general practitioners ' electronic medical records . The system is based on the guidelines for asthma and chronic obstructive pulmonary disease ( COPD ) as issued by the Dutch College of General Practitioners . This paper assesses the effect of AsthmaCritic on monitoring and treatment of asthma and COPD by Dutch general practitioners in daily practice . METHODS A r and omized clinical trial in 32 practice s ( 40 Dutch general practitioners ) using electronic patient records . An intervention group was given the use of AsthmaCritic , a control group continued working in the usual manner . Both groups had the disposal of the asthma and COPD guidelines routinely distributed by the Dutch College of General Practitioners . We measured the average number of contacts , FEV 1 ( forced expiratory volume ) , and peak-flow measurements per asthma/ COPD patient per practice ; and , the average number of antihistamine , cromoglycate , deptropine , and oral bronchodilator prescriptions per asthma/ COPD patient per practice . RESULTS The number of contacts increased in the age group of 12 - 39 years . The number of FEV1 , peak-flow measurements , and the ratio of coded measurements increased , whereas the number of cromoglycate prescriptions decreased in the age group of 12 - 39 years . CONCLUSIONS Our study shows that the guideline -based critiquing system AsthmaCritic changed the manner in which the physicians monitored their patients and , to a lesser extent , their treatment behavior . In addition , the physicians changed their data -recording habits AIM To evaluate patient underst and ing of their asthma and determine patient preferences regarding the delivery of asthma care and treatment . METHODS Adults with asthma receiving treatment for mild to moderate asthma were recruited to a two-part study : a qualitative phase using a semi-structured interview schedule followed by a quantitative phase based on a structured interview schedule . All interviews were undertaken face-to-face . SETTING AND SUBJECTS A r and om sample of 40 patients with mild to moderate asthma from seven areas of the UK took part in the qualitative phase of the study . In the quantitative phase , 517 patients on treatment for mild to moderate asthma were interviewed in person by market research ers . This population was achieved using a quota sampling approach that also achieved a representative demographic profile . Initial contact was made in door-to-door calls . Interviews took place in 64 locations across the UK . RESULTS Ninety-one percent ( n=468 ) of respondents felt their asthma was under control , yet two-thirds ( n=339 ) experienced symptoms at least 2 - 3 times a week . Only 24 % ( n=123 ) felt their asthma could improve over time , and 71 % ( n=366 ) received no advice from healthcare professionals on how their asthma might change in the future . Fourteen percent ( n=74 ) of respondents had no ongoing contact with any healthcare professional regarding their asthma . Fifty-eight percent ( n=301 ) were very satisfied with their asthma care , but this dropped to 33 % ( n=173 ) when respondents were shown asthma guidelines regarding what to expect from treatment . Sixty-two percent ( n=318 ) of respondents said their asthma varied at different times of the day , and 86 % ( n=444 ) stated that their asthma varied at different times of the year . Eighty percent ( n=414 ) of respondents had never been provided with a written , personal asthma action plan recommending changes patients could make themselves to prescribed treatment according to symptom severity , though 68 % ( n=353 ) said they would feel comfortable following such a plan . CONCLUSIONS Most patients have low expectations of what can be achieved by asthma management and do not realise their condition can be improved . Many are resigned to the effects of poor asthma control until made aware that guidelines indicate this can be better . Given that many are receptive to the notion of written , personal asthma action plans , the implementation of these , supported by appropriate education , could help patients achieve improved asthma control OBJECTIVE It is difficult to control drug-prescribing behaviour in general practice , despite the development and distribution of guidelines . The purpose of this study was to assess the effect on drug-prescribing behaviour of implementing prescribing guidelines by means of a reactive computer reminder system ( CRS ) . DESIGN Cluster-r and omised controlled trial with an incomplete block design in the south of the Netherl Output:	Overall , CDSSs for professionals were ineffective . Usage of the systems was generally low : in the only trial at low risk of bias the CDSS was not used at all . When a CDSS was used , compliance with the advice offered was also low . However , if actually used , CDSSs could result in closer guideline adherence ( improve investigating , prescribing and issuing of action plans ) and could improve some clinical outcomes . The study at moderate risk of bias showed increased prescribing of inhaled steroids . Conclusions : The current generation of CDSSs is unlikely to result in improvements in outcomes for patients with asthma because they are rarely used and the advice is not followed .
MS21225	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: In a prospect i ve , r and omized , controlled trial , we compared sulbactam/cefoperazone with imipenem as empirical monotherapy for febrile , granulocytopenic patients ; 101 patients received sulbactam/cefoperazone ( 2 g/4 g every 12 hours ) and 102 patients received imipenem ( 500 mg every 6 hours ) . Documented infections were present in 40 % of patients treated with sulbactam/cefoperazone ( 40 of 101 ) and in 39 % of patients receiving imipenem ( 40 of 102 ) . The number of pretherapy gram-positive pathogens ( 52 isolates ) was twice the number of pretherapy gram-negative pathogens ( 26 isolates ) . The overall favorable clinical response rates for sulbactam/cefoperazone ( 91 of 103 patients , or 88 % ) and imipenem ( 84 of 104 patients , or 81 % ) were similar . Both drugs were generally well tolerated . However , diarrhea occurred more often in patients treated with sulbactam/cefoperazone ( 31 of 101 patients , or 31 % , vs. 15 of 102 patients , or 15 % ; P = .007 ) , while seizures developed only in patients receiving imipenem ( 0 of 101 patients vs. 3 of 102 patients , or 3 % ) . Superinfections developed in 16 % of patients in both study groups but were infrequently caused by beta-lactam-resistant gram-negative bacilli ( two cases with sulbactam/cefoperazone therapy and six cases with imipenem ) . These results support the efficacy and safety of either sulbactam/cefoperazone or imipenem as empirical monotherapy for febrile granulocytopenic patients OBJECTIVE : To compare the efficacies of cefepime and ceftazidime as empiric therapy during the management of fever in cancer patients with chemotherapy-induced neutropenia . METHODS : A prospect i ve , double-blind , r and omized study of cefepime 2 g every eight hours and ceftazidime 2 g every eight hours was performed in 276 adult neutropenic ( absolute neutrophil count < 500/mm3 ) cancer patients with fever . RESULTS : Median duration of neutropenia was five days . Sixty-one percent ( n = 188 ) of the patients were evaluable . Treatment was successful in 57 % ( 58/101 ) of cefepime-treated patients and 60 % ( 52/87 ) of ceftazidime-treated patients ( 95 % CI −18 to 12 ; p = 0.77 ) . Bacteremic clearance occurred in 71 % ( 12/17 ) of cefepime-treated patients and 40 % ( 6/15 ) of ceftazidime-treated patients ( p = 0.3 ) . Both drugs were well tolerated . CONCLUSIONS : Cefepime appears to be as effective as ceftazidime in the initial treatment of febrile episodes in adult cancer patients with chemotherapy-associated neutropenia of modest duration BACKGROUND With the availability of new broad-spectrum antibiotics , initial therapy with a single agent has become an alternative to classic combinations , especially beta-lactam antibiotics plus aminoglycosides , in the management of febrile neutropenic cancer patients . PROCEDURE Since January 1994 , monotherapy has been used for empiric initial treatment at our center . The aim of this prospect i ve r and omized study is to compare the efficacy of cefepime ( CFP ) , a new fourth-generation cephalosporin , and ceftazidime ( CFZ ) as empirical monotherapy of febrile neutropenic patients with solid tumors . From January 1998 to November 1998 , 63 episodes of fever and neutropenia occurring in 33 children with solid tumors including lymphomas , were r and omized to receive treatment with either CFP or CFZ . The patients were analyzed for leukocyte count and absolute neutrophil count ( ANC ) at entry , days in fever , neutropenia and hospitalization , and side effects of drugs . Success with or without modifications of the initial antibiotic was defined as survival through neutropenia ; failure was death due to infection . RESULTS In our study group , with a median age of 7 [ (1/12)-14 ] years , CFP was administered in 32 , and CFZ in 31 episodes . An infection was documented microbiologically in eight episodes ( 25 % ) in the CFP arm and in nine episodes ( 29 % ) in the CFZ arm . The success rate with initial empiric monotherapy was 62.5 % in the CFP arm and 61.3 % in the CFZ arm respectively ( P > 0.05 ) . The total success rate ( success with or without modification ) was 100 % in both arms . No major adverse effects were observed in either groups . CONCLUSION CFP is as effective and safe as CFZ for the empirical treatment of febrile episodes in neutropenic patients with solid tumors Abstract A total of 101 cancer patients with 121 febrile neutropenia episodes were r and omised to receive empirical treatment with i.v . meropenem ( 1 g/8 h ) or ceftazidime ( 2 g/8 h ) . After 3 days , 89 % of patients were on unmodified therapy in the meropenem group , compared with 83 % in the ceftazidime group . Of the evaluable episodes ( n=106 ) , the success rate with unmodified empirical therapy until the end of the treatment course was slightly higher with meropenem than with ceftazidime ( 48 % vs 38 % , P=0.39 ) . Furthermore , initial success with further infections was observed in 22 % of episodes treated with meropenem and in 13 % of episodes treated with ceftazidime . Glycopeptides were used as first modification in 28 % and 39 % of meropenem and ceftazidime recipients , respectively . Both treatments were well tolerated and there were no reports of drug-related nausea/vomiting or seizures . No significant differences in response rate or in tolerability were observed when analysing only the first febrile episodes . In conclusion , meropenem seems to be as efficacious and well tolerated as ceftazidime and may be associated with a lesser requirement for the addition of glycopeptides Serum procalcitonin ( PCT ) levels have been proposed as a new discriminative marker for bacterial and fungal infections . We analysed the diagnostic relevance of PCT in febrile episodes of neutropenic adult patients after haematopoietic stem cell transplantation ( HSCT ) . PCT was determined prospect ively in 92 febrile episodes , classified according to the final diagnosis as : neutropenic fever of unknown origin ( n = 51 ) , microbiological ( n = 26 ) or clinical ( n = 5 ) documented infection and non‐infectious febrile episodes ( n = 10 ) . On first day of fever , mean ( ±SD ) PCT level was 0·3 ng/ml ( 0·2 ) in neutropenic fever of unknown origin , 0·5 ng/ml ( 0·7 ) in microbiologically confirmed infections , 0·2 ng/ml ( 0·2 ) in clinical ly documented infections and 1·7 ( 4·2 ) in non‐infectious fever ( P = not significant ) . Five days after the antibiotic therapy was started , fever persisted in 29 neutropenic episodes ( 32 % ) . Cases that were eventually diagnosed with invasive aspergillosis had PCT values significantly higher [ 10·1 ng/ml ( 6·7 ) ] than all remaining groups ( P = 0·027 ; Kruskal – Wallis ) . Our analysis indicates that the PCT level on first day of fever did not facilitate the differential diagnosis of neutropenic febrile episode . However , when fever persisted for more than 5 d , PCT values ≥3 ng/ml had a high sensitivity and specificity for the diagnosis of invasive aspergillosis This open , comparative , r and omized , multicentre equivalence study compared cefepime 2 g bd and imipenem-cilastatin 1 g tds ( 50 mg/kg/day ) as empirical monotherapy for febrile episodes in a homogeneous cohort of cancer patients with short duration neutropenia following chemotherapy for solid tumour , lymphoma or myeloma . The study was conducted in 17 French anti-cancer centres in 1995 and 1996 . Response to monotherapy was assessed 7 days after treatment and was based on resolution of fever and signs and symptoms , eradication of pathogens , absence of new infection , relapse , and death of infectious origin , without addition of other antibiotics . Patients were treated for a minimum of 4 days . Of the 400 episodes r and omized , 344 ( 86 % ) were evaluable for efficacy . Patient characteristics were comparable between treatment groups . Success of monotherapy was observed in 79 % of episodes with cefepime and 72 % with imipenem-cilastatin ( equivalence , P < 0.0001 ) . The response rate for microbiologically documented infections was 66 % with cefepime and 61 % with imipenem-cilastatin ( bacteraemic episodes : 63 % for cefepime ; 44 % for imipenem-cilastatin ) . A second antibiotic ( usually a glycopeptide ) was added in 20 % and 21 % of the cases , respectively . Overall , the response to therapy , with or without an additional antibiotic , was 95 % ( cefepime ) and 90 % ( imipenem-cilastatin ) . Survival was similar in both groups ( 95 % and 98 % , respectively ) . Cefepime treatment was better tolerated , with 9 % of the patients experiencing related intercurrent events compared with 19 % in the imipenem-cilastatin group ( P = 0.003 ) . Nausea/vomiting was significantly more frequent in the imipenem-cilastatin group ( 15 % ) than in the cefepime group ( 5 % ; P = 0.001 ) . Cefepime monotherapy was as effective as , and better tolerated than , imipenem-cilastatin in the empirical treatment of fever during short duration neutropenia Background . Monotherapy with cefepime or ceftazidime is an effective alternative to combination therapy for the treatment of febrile neutropenic adult cancer patients . We compared the efficacy and safety of cefepime and ceftazidime as empiric monotherapy of febrile neutropenia in children with cancer . Material s and methods . A prospect i ve , open label , r and omized , comparative study in pediatric cancer patients was conducted at Chang Gung Children ’s Hospital from January 1 , 2000 , to April 15 , 2001 . Patients with fever and neutropenia ( absolute neutrophil count of ≤500/mm3 ) were r and omized to receive either intravenous cefepime or ceftazidime ( 50 mg/kg/dose as two or three doses daily ) . Febrile episodes were classified as microbiologically documented infection , clinical ly documented infection or unexplained fever . Clinical response to therapy was classified as success and failure . Results . Ninety-five pediatric cancer patients with 120 febrile neutropenic episodes were r and omized to receive empiric treatment with cefepime or ceftazidime . After 72 h of treatment , 82.8 % ( 48 of 58 ) of the eligible patients in the cefepime group continued with unmodified therapy , compared with 87.9 % ( 51 of 58 ) in the ceftazidime group . The neutrophil count was < 100/mm3 at r and omization for 76 % of the patients in the cefepime group and 83 % of those in the ceftazidime group ; the median duration s of neutropenia ( < 500/mm3 ) were 8.5 and 6.5 days , respectively . Of the 96 evaluable episodes the overall success rate with unmodified empiric therapy until the end of the treatment course in the cefepime group was comparable with that in the ceftazidime group ( 69%vs . 71 % , P = 0.95 ) . The response rate after glycopeptides were added to the regimens was 79.2 % for the cefepime group and 77.1 % for the ceftazidime group . The bacterial eradication rate was 33 % for the cefepime group and 20 % for the ceftazidime group ( P = 0.85 ) , and the rates of new infections were 10.4%vs . 4.2 % ( P = 0.67 ) , respectively . Both study drugs were well-tolerated . Three ( 6.4 % ) patients in the cefepime group and 2 ( 4.3 % ) patients in the ceftazidime group died . Conclusion . Cefepime appeared to be as effective and safe as ceftazidime for empiric treatment of febrile episodes in neutropenic pediatric cancer patients 1998 , a consensus meeting was held in Miyazaki , Japan , to develop an approach to management of febrile neutropenia ( FN ) . The K‐HOT study group decided to examine whether this proposal was applicable to clinical practice in a multicenter study . Patients who developed fever with neutrophil counts < 1,000/μL were r and omized to receive either a single antibiotic Output:	Carbapenems were associated with fewer treatment modifications , including addition of glycopeptides , than ceftazidime or other comparators . No significant differences were demonstrated with paucity of data for all-cause mortality . Empirical use of carbapenems entails fewer treatment modifications , but an increased rate of pseudomembranous colitis . Ceftazidime , piperacillin/tazobactam , imipenem/cilastatin and meropenem appear to be suitable agents for monotherapy
MS21226	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Cardiac-surgery-associated-acute-kidney-injury ( CSA-AKI ) is associated with increased morbidity and mortality . Recent data from patients undergoing on-pump coronary artery bypass grafting suggest that a perioperative infusion of sodium-bicarbonate may decrease the incidence of CSA-AKI . The present study aims to analyze the renoprotective effects of a 24h infusion of sodium-bicarbonate in a large , heterogeneous group of cardiac surgical patients Methods Starting in 4/2009 , all patients undergoing cardiac surgery at our institution were enrolled in a prospect i ve trial analyzing the relationship between preoperative cerebral oxygen saturation and postoperative organ dysfunction . We used this prospect ively sample d data set to perform a cohort analysis of the renoprotective efficiency of a 24h continuous perioperative infusion of sodium-bicarbonate on the incidence of CSA-AKI that was routinely introduced in 7/2009 . After exclusion of patients with endstage chronic kidney disease , off-pump procedures , and emergency cases , perioperative changes in renal function were assessed in 280 patients treated with a perioperative infusion of 4 mmol sodium-bicarbonate / kg body weight in comparison with a control cohort of 304 patients enrolled from April to June in this prospect i ve cohort study .Postoperative changes in urine flow , plasma creatinine , estimated creatinine clearance , and the need for renal replacement therapy were determined according to AKI injury network criteria . Concomitantly , hemodynamics , treatments , complications , and clinical outcomes were recorded . Univariate statistical analyses were performed para- and nonparametrically , as appropriate . Results With the exception of a lower prevalence of a history of myocardial infa rct ion and a lower preoperative use of intravenous heparin in the bicarbonate-group , no significant between group differences in patient demographics , surgical risk , type , and duration of surgery were observed . Patients in the bicarbonate group had a lower mean arterial blood pressure after induction of anesthesia , needed more fluids , more vasopressors , and a longer treatment time in the high dependency unit . Despite a higher postoperative diuresis , no differences in the incidence of AKI grade 1 to 3 and the need for renal replacement were observed . Conclusions Routine perioperative administration of sodium bicarbonate failed to improve postoperative renal function in a large population of cardiac surgical patients " Recommendations for the management of crush victims in mass disasters " aims to assist medics , paramedics and rescue team members who provide care during disasters . Development of the recommendations followed an explicit process of literature review and , also internet and face-to-face discussion s. The chapters cover medical and logistic measures , to be taken both at the disaster field and in the hospitals , to cope with the problems created by a catastrophe . Recommendations were based on retrospective analyses and case reports on past disasters , and also expert judgment or opinion . Since there are no r and omized controlled trials , no GRADE approach was used to develop the recommendations , and no strengths of recommendations or levels of evidence are provided CONTEXT Contrast-induced nephropathy remains a common complication of radiographic procedures . Pretreatment with sodium bicarbonate is more protective than sodium chloride in animal models of acute ischemic renal failure . Acute renal failure from both ischemia and contrast are postulated to occur from free-radical injury . However , no studies in humans or animals have evaluated the efficacy of sodium bicarbonate for prophylaxis against contrast-induced nephropathy . OBJECTIVE To examine the efficacy of sodium bicarbonate compared with sodium chloride for preventive hydration before and after radiographic contrast . DESIGN , SETTING , AND PATIENTS A prospect i ve , single-center , r and omized trial conducted from September 16 , 2002 , to June 17 , 2003 , of 119 patients with stable serum creatinine levels of at least 1.1 mg/dL ( > or = 97.2 micromol/L ) who were r and omized to receive a 154-mEq/L infusion of either sodium chloride ( n = 59 ) or sodium bicarbonate ( n = 60 ) before and after iopamidol administration ( 370 mg iodine/mL ) . Serum creatinine levels were measured at baseline and 1 and 2 days after contrast . INTERVENTIONS Patients received 154 mEq/L of either sodium chloride or sodium bicarbonate , as a bolus of 3 mL/kg per hour for 1 hour before iopamidol contrast , followed by an infusion of 1 mL/kg per hour for 6 hours after the procedure . MAIN OUTCOME MEASURE Contrast-induced nephropathy , defined as an increase of 25 % or more in serum creatinine within 2 days of contrast . RESULTS There were no significant group differences in age , sex , incidence of diabetes mellitus , ethnicity , or contrast volume . Baseline serum creatinine was slightly higher but not statistically different in patients receiving sodium bicarbonate treatment ( mean [ SD ] , 1.71 [ 0.42 ] mg/dL [ 151.2 [ 37.1 ] micromol/L ] for sodium chloride and 1.89 [ 0.69 ] mg/dL [ 167.1 [ 61.0 ] micromol/L ] for sodium bicarbonate ; P = .09 ) . The primary end point of contrast-induced nephropathy occurred in 8 patients ( 13.6 % ) infused with sodium chloride but in only 1 ( 1.7 % ) of those receiving sodium bicarbonate ( mean difference , 11.9 % ; 95 % confidence interval [ CI ] , 2.6%-21.2 % ; P = .02 ) . A follow-up registry of 191 consecutive patients receiving prophylactic sodium bicarbonate and meeting the same inclusion criteria as the study result ed in 3 cases of contrast-induced nephropathy ( 1.6 % ; 95 % CI , 0%-3.4 % ) . CONCLUSION Hydration with sodium bicarbonate before contrast exposure is more effective than hydration with sodium chloride for prophylaxis of contrast-induced renal failure In a double-blinded r and omized controlled trial , Anja Haase-Fielitz and colleagues find that an infusion of sodium bicarbonate during open heart surgery did not reduce the risk for acute kidney injury , compared with saline control Background Acute kidney injury ( AKI ) requiring renal replacement therapy ( RRT ) is associated with high in-hospital morbidity and mortality in critically ill patients . Long-term outcomes have received little attention . Methods The aim of this study was to characterize AKI – chronic kidney disease ( CKD ) nexus in critically ill patients with AKI ( RIFLE class F ) . We performed a single-centre prospect i ve observational study of 425 consecutive critically ill patients with AKI requiring RRT . None of these patients had pre-existing kidney disease . Primary outcomes were vital status and renal function at hospital discharge and at 5 and 10 years of follow-up . Results The overall in-hospital mortality of the study cohort was 47 % , the mortality rates at 1 , 5 and 10 years were 65 , 75 and 80 % , respectively . At hospital discharge , recovery of renal function was complete in 56 % of survivors . None of these patients developed CKD during follow-up . Ninety percent of the 100 survivors with partial recovery of renal function had ongoing CKD during long-term follow-up . CKD progressed to end-stage renal disease ( ESRD ) in 12 patients ( 3 % of the cohort or 5 % of survivors ) . The patients with post-AKICKD had a higher prevalence of hypertension , a higher rate of fatal cardiac diseases and a higher all-cause death rate . Conclusion Long-term survival of critically ill patients with AKI requiring RRT is poor and determined by the development of de novo CKD . There is a need for close follow-up of patients surviving AKI to prevent progressive CKD and to reduce associated lethal cardiac events Iodine and gadolinium-based contrast induced nephropathy is the third leading cause of hospital-acquired acute kidney injury . It is essentially observed in patients with defined risk factors and is associated with increased morbidity and mortality . The prevention of contrast induced nephropathy consists in volume expansion through intravenous sodium chloride 0.9 % or sodium bicarbonate 1.4 % . Comparative r and omized controlled trials appear to show a benefit in favor of sodium bicarbonate over saline fluids . According to last evidence , N-acetylcysteine does not provide additional benefit over intravenous fluids BACKGROUND There is controversy about the prophylactic measures proposed for the prevention of contrast-induced nephropathy ( CIN ) . We aim to compare the efficacy of the combination of sodium bicarbonate and isotonic saline and that of isotonic saline alone in preventing CIN . STUDY DESIGN R and omized double-blind controlled trial . SETTING & PARTICIPANTS 265 consecutive patients 18 years or older with a serum creatinine level of 1.5 mg/dL or greater undergoing elective coronary angiography from August 2007 to June 2008 in Tehran Heart Center , Tehran , Iran . INTERVENTION Study participants were r and omly assigned to receive either 75 mL of 8.4 % sodium bicarbonate added to 1 L of isotonic saline ( n = 135 ) or isotonic saline alone ( n = 130 ) as a bolus of 3 mL/kg for 1 hour before contrast injection , followed by an infusion of 1 mL/kg/h for 6 hours after the procedure . OUTCOMES & MEASUREMENTS The primary end point was an absolute ( > or=0.5 mg/dL ) or relative ( > or=25 % ) increase in serum creatinine level 48 hours after the procedure ( CIN ) . RESULTS There were no significant differences between the bicarbonate and saline groups regarding baseline demographic and biochemical characteristics , including baseline serum creatinine level ( 1.63 + /- 0.32 [ SD ] versus 1.66 + /- 0.50 mg/dL ) , baseline glomerular filtration rate ( 46.4 + /- 12 versus 45.4 + /- 12 mL/min/1.73 m(2 ) ) , and baseline urine pH ( 5.42 + /- 0.6 versus 5.46 + /- 0.8 ) . Nine patients ( 7.4 % ) receiving sodium bicarbonate developed CIN as opposed to 7 patients ( 5.9 % ) in the saline group , which was not statistically different ( odds ratio , 1.26 ; 95 % confidence interval , 0.45 to 3.50 ; P = 0.6 ) . LIMITATIONS The trial did not follow up participants to assess need for dialysis and mortality rate . CONCLUSION The combination therapy of sodium bicarbonate plus saline does not offer additional benefits over hydration with saline alone in the prevention of CIN Objectives : Cardiac surgery – associated acute kidney injury occurs in up to 50 % of patients and is associated with increased mortality and morbidity . This study aim ed to discover if perioperative urinary alkalinization with sodium bicarbonate infusion reduces the prevalence of cardiac surgery – associated acute kidney injury . Design : This study was a phase IIb multicenter double-blind r and omized controlled trial . Setting : This study was conducted in three tertiary hospitals in New Zeal and and Australia . Patients : A total of 427 patients scheduled to undergo elective cardiac surgery , who were at increased risk of development of cardiac surgery – associated acute kidney injury using recognized risk factors . Measurements and Main Results : Patients were r and omly allocated to receive either sodium bicarbonate ( n = 215 ) or sodium chloride ( n = 212 ) infusion , commencing at the start of anesthesia , in a dose of 0.5 mEq/kg/hr for the first hour and then 0.2 mmol/kg/hr for 23 hours . The primary outcome measure was the number of patients with development of cardiac surgery – associated acute kidney injury , defined as an increase in creatinine greater than 25 % or 0.5 mg/dL ( 44 µmol/L ) from baseline to peak value within the first five postoperative days . Significant differences among the groups in both plasma and urinary biochemistry were achieved 6 hours after commencement of the infusion , and these changes persisted for more than 24 hours . A total of 100 out of 215 patients ( 47 % [ 95 % CI , 40%–53 % ] ) in the sodium bicarbonate group and 93 of 212 patients ( 44 % [ 95 % CI , 37%–51 % ] ) in the sodium chloride group with development of acute kidney injury within the first five postoperative days ( p = 0.58 ) . There were also no significant differences in ventilation hours , ICU or hospital length of stay , or mortality . Conclusions : Perioperative alkalinization of blood and urine using an infusion of sodium b Output:	Based on current literature , intravenous sodium bicarbonate does not seem to be more efficient than saline for the prevention of contrast-media-induced AKI , cardiac surgery-associated AKI , pigment nephropathy or septic AKI . However , some cohort studies or prospect i ve r and omized trials did track and report serious adverse events , such as higher rates of AKI or higher in-hospital mortality .
MS21227	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Eighty-nine patients who had been treated by ileal resection for Crohn 's disease between 1979 and 1984 were included in a prospect i ve cohort follow up to study the natural course of early postoperative lesions . Recurrent lesions were observed endoscopically in the neoterminal ileum within 1 year of surgery in 73 % of the patients , although only 20 % of the patients had symptoms . Three years after surgery , the endoscopic recurrence rate had increased to 85 % and symptomatic recurrence occurred in 34 % . The ultimate course of the disease was best predicted by the severity of the early postoperative lesions , as observed at ileoscopy . Clinical parameters that influenced outcome were preoperative disease activity , the indication for surgery , and the number of surgical resections . When patients were stratified for preoperative disease activity , the severity of lesions found at endoscopy remained a strong predictive factor for symptomatic recurrence . In 22 other patients su bmi tted to " curative " ileal resection and ileocolonic anastomosis , the segment to be used as neoterminal ileum was carefully examined during surgery , and two large biopsies were taken before making the anastomosis . An ileoscopy was performed 6 months after surgery . Although all patients had a macroscopically normal neoterminal ileum and 19 had entirely normal biopsies at the time of surgery , 21 patients were found at ileoscopy to have developed ileitis involving a 15-cm segment ( range , 4 - 30 cm ) , and 20 had unequivocal microscopic lesions on biopsies . These studies suggest that early lesions in the neoterminal ileum after Crohn 's resection do not originate from microscopic inflammation present in this bowel segment at the time of surgery . The early postoperative lesions in the neoterminal ileum seem to be a suitable model to study the pathogenesis of Crohn 's disease and also to evaluate new therapeutic modalities , either to prevent development of these early lesions or to treat progressive recurrence Background : Probiotics are efficacious for treating and maintaining remission of ulcerative colitis OBJECTIVES : VSL#3 is a high-potency probiotic mixture that has been used successfully in the treatment of pouchitis . The primary end point of the study was to assess the effects of supplementation with VSL#3 in patients affected by relapsing ulcerative colitis ( UC ) who are already under treatment with 5-aminosalicylic acid ( ASA ) and /or immunosuppressants at stable doses . METHODS : A total of 144 consecutive patients were r and omly treated for 8 weeks with VSL#3 at a dose of 3,600 billion CFU/day ( 71 patients ) or with placebo ( 73 patients ) . RESULTS : In all , 65 patients in the VSL#3 group and 66 patients in the placebo group completed the study . The decrease in ulcerative colitis disease activity index ( UCDAI ) scores of 50 % or more was higher in the VSL#3 group than in the placebo group ( 63.1 vs. 40.8 ; per protocol ( PP ) P=0.010 , confidence interval (CI)95 % 0.51–0.74 ; intention to treat ( ITT ) P=0.031 , CI95 % 0.47–0.69 ) . Significant results with VSL#3 were recorded in an improvement of three points or more in the UCDAI score ( 60.5 % vs. 41.4 % ; PP P=0.017 , CI95 % 0.51–0.74 ; ITT P=0.046 , CI95 % 0.47–0.69 ) and in rectal bleeding ( PP P=0.014 , CI95 % 0.46–0.70 ; ITT P=0.036 , CI95 % 0.41–0.65 ) , whereas stool frequency ( PP P=0.202 , CI95 % 0.39–0.63 ; ITT P=0.229 , CI95 % 0.35–0.57 ) , physician 's rate of disease activity ( PP P=0.088 , CI95 % 0.34–0.58 ; ITT P=0.168 , CI95 % 0.31–0.53 ) , and endoscopic scores ( PP P=0.086 , CI95 % 0.74–0.92 ; ITT P=0.366 , CI95 % 0.66–0.86 ) did not show statistical differences . Remission was higher in the VSL#3 group than in the placebo group ( 47.7 % vs. 32.4 % ; PP P=0.069 , CI95 % 0.36–0.60 ; ITT P=0.132 , CI95 % 0.33–0.56 ) . Eight patients on VSL#3 ( 11.2 % ) and nine patients on placebo ( 12.3 % ) reported mild side effects . CONCLUSIONS : VSL#3 supplementation is safe and able to reduce UCDAI scores in patients affected by relapsing mild-to-moderate UC who are under treatment with 5-ASA and /or immunosuppressants . Moreover , VSL#3 improves rectal bleeding and seems to reinduce remission in relapsing UC patients after 8 weeks of treatment , although these parameters do not reach statistical significance BACKGROUND & AIMS Saccharomyces boulardii is a probiotic yeast that has been shown to have beneficial effects on the intestinal epithelial barrier and digestive immune system . There is preliminary evidence that S boulardii could be used to treat patients with Crohn 's disease ( CD ) . We performed a r and omized , placebo-controlled trial to evaluate the effects of S boulardii in patients with CD who underwent remission during therapy with steroids or aminosalicylates . METHODS We performed a prospect i ve study of 165 patients who achieved remission after treatment with steroids or salicylates ; they were r and omly assigned to groups given S boulardii ( 1 g/day ) or placebo for 52 weeks . The primary end point was the percentage of patients in remission at week 52 . Time to relapse , Crohn 's disease activity index scores , and changes in parameters of inflammation were secondary end points . RESULTS CD relapsed in 80 patients , 38 in the S boulardii group ( 47.5 % ) and 42 in the placebo group ( 53.2 % , a nonsignificant difference ) . The median time to relapse did not differ significantly between patients given S boulardii ( 40.7 weeks ) vs placebo ( 39.0 weeks ) . There were no significant differences between groups in mean Crohn 's disease activity index scores or erythrocyte sedimentation rates or in median levels of C-reactive protein . In a post hoc analysis , nonsmokers given S boulardii were less likely to experience a relapse of CD than nonsmokers given placebo , but this finding requires confirmation . CONCLUSIONS Although the probiotic yeast S boulardii is safe and well tolerated , it does not appear to have any beneficial effects for patients with CD in remission after steroid or salicylate therapies AIM To investigate the effects of probiotic on intestinal mucosae of patients with ulcerative colitis ( UC ) , and to evaluate the role of probiotic in preventing the relapse of UC . METHODS Thirty patients received treatment with sulphasalazine ( SASP ) and glucocorticoid and then were r and omly administered bifid triple viable capsule ( BIFICO ) ( 1.26 g/d ) , or an identical placebo ( starch ) for 8 wk . Fecal sample s were collected for stool culture 2 wk before and after the r and omized treatments . The patients were evaluated clinical ly , endoscopically and histologically after 2 mo of treatment or in case of relapse of UC . p65 and IkappaB expressions were determined by Western blot analysis . DNA-binding activity of NF-kappaB in colonic nuclear extracts was detected by electrophoretic mobility shift assay ( EMSA ) . mRNA expressions of cytokines were identified by semi-quantitative assay , reverse transcriptase- polymerase chain reaction ( RT-PCR ) . RESULTS Three patients ( 20 % ) in the BIFICO group had relapses during 2-mo follow-up period , compared with 14 ( 93.3 % ) in placebo group ( P<0.01 ) . The concentration of fecal lactobacilli , bifidobacteria was significantly increased in BIFICO-treated group only ( P<0.01 ) . The expressions of NF-kappaB p65 and DNA binding activity of NF-kappaB were significantly attenuated in the treatment group than that in control ( P<0.05 ) . The mRNA expression of anti-inflammatory cytokines was elevated in comparison with the control group . CONCLUSION The probiotic could impede the activation of NF-kappaB , decrease the expressions of TNF-alpha and IL-1beta and elevate the expression of IL-10 . These results suggest that oral administration of this new probiotic preparation is effective in preventing flare-ups of chronic UC . It may become a prophylactic drug to decrease the relapse of UC Background and aims : Experimental studies have shown that luminal bacteria may be involved in Crohn 's disease . Probiotics are a possible alternative to antibiotics . The aim of this r and omised placebo controlled study was to determine if Lactobacillus GG , given by mouth for one year , could prevent Crohn 's recurrent lesions after surgery or to reduce their severity . Methods : Patients operated on for Crohn 's disease in whom all of the diseased gut had been removed were r and omly allocated to receive 12 billion colony forming units of Lactobacillus or identical placebo for one year . Ileocolonoscopy was performed at the end of the trial or at the onset of symptoms . Endoscopic recurrence was defined as grade 2 or higher of Rutgeerts scoring system . Results : Eight of 45 patients were excluded from the trial ( three for non-compliance and five for protocol violations ) . Clinical recurrence was ascertained in three ( 16.6 % ) patients who received Lactobacillus and in two ( 10.5 % ) who received placebo . Nine of 15 patients in clinical remission on Lactobacillus ( 60 % ) had endoscopic recurrence compared with six of 17 ( 35.3 % ) on placebo ( p=0.297 ) . There were no significant differences in the severity of the lesions between the two groups . Conclusions : Lactobacillus GG seems neither to prevent endoscopic recurrence at one year nor reduce the severity of recurrent lesions Background Experimental studies have shown that luminal antigens are involved in chronic intestinal inflammatory disorders such as Crohn 's disease and ulcerative colitis . Alteration of the intestinal microflora by antibiotic or probiotic therapy may induce and maintain remission . The aim of this r and omized , placebo-controlled trial was to determine the effect of oral Lactobacillus GG ( L. GG ) to induce or maintain medically induced remission . Methods Eleven patients with moderate to active Crohn 's disease were enrolled in this trial to receive either L. GG ( 2 × 109 CFU/day ) or placebo for six months . All patients were started on a tapering steroid regime and received antibiotics for the week before the probiotic/placebo medication was initiated . The primary end point was sustained remission , defined as freedom from relapse at the 6 months follow-up visit . Relapse was defined as an increase in CDAI of > 100 points . Results 5/11 patients finished the study , with 2 patients in each group in sustained remission . The median time to relapse was 16 ± 4 weeks in the L. GG group and 12 ± 4.3 weeks in the placebo group ( p = 0.5 ) . Conclusion In this study we could not demonstrate a benefit of L. GG in inducing or maintaining medically induced remission in CD Guidelines for clinical practice are intended to suggest preferable approaches to particular medical problems as established by interpretation and collation of scientifically valid research , derived from extensive review of published literature . When data that will withst and objective scrutiny are not available , a recommendation may be made based on a consensus of experts . Guidelines are intended to apply to the clinical situation for all physicians without regard to specialty . Guidelines are intended to be flexible , not necessarily indicating the only acceptable approach , and should be distinguished from st and ards of care that are inflexible and rarely violated . Given the wide range of choices in any health-care problem , the physician should select the course best suited to the individual patient and the clinical situation presented . These guidelines are developed under the auspices of the American College of Gastroenterology and its Practice Parameters Committee . Expert opinion is solicited from the outset for the document . The quality of evidence upon which a specific recommendation is based is as follows : Grade A : Homogeneous evidence from multiple well- design ed r and omized ( therapeutic ) or cohort ( descriptive ) controlled trials , each involving a number of participants to be of sufficient statistical power . Grade B : Evidence from at least one large well- design ed clinical trial with or without r and omization , from cohort or case – control analytic studies , or well- design ed meta- analysis . Grade C : Evidence based on clinical experience , descriptive studies , or reports of expert committees . The Committee review s guidelines in depth , with participation from experienced clinicians and others in related fields . The final recommendations are Output:	VSL#3 may be effective in inducing remission in active UC . Probiotics may be as effective as 5-ASAs in preventing relapse of quiescent UC .
MS21228	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Players are the targeted end-users and beneficiaries of exercise-training programmes implemented during coach-led training sessions , and the success of programmes depends upon their active participation . Two variants of an exercise-training programme were incorporated into the regular training schedules of 40 community Australian Football teams , over two seasons . One variant replicated common training practice s , while the second was an evidence -based programme to alter biomechanical and neuromuscular factors related to risk of knee injuries . This paper describes the structure of the implemented programmes and compares players ’ end-of-season views about the programme variants . Methods This study was nested within a larger group-clustered r and omised controlled trial of the effectiveness of two exercise-training programmes ( control and neuromuscular control ( NMC ) ) for preventing knee injuries . A post-season self-report survey , derived from Health Belief Model constructs , included questions to obtain players ’ views about the benefits and physical challenges of the programme in which they participated . Results Compared with control players , those who participated in the NMC programme found it to be less physically challenging but more enjoyable and potentially of more benefit . Suggestions from players about potential improvements to the training programme and its future implementation included reducing duration , increasing range of drills/exercises and promoting its injury prevention and other benefits to players . Conclusions Players provide valuable feedback about the content and focus of implemented exercise-training programmes , that will directly inform the delivery of similar , or more successful , programmes in the future Background A protective effect on injury risk in youth sports through neuromuscular warm-up training routines has consistently been demonstrated . However , there is a paucity of information regarding the quantity and quality of coach-led injury prevention programmes and its impact on the physical performance of players . Objective The aim of this cluster-r and omised controlled trial was to assess whether different delivery methods of an injury prevention programme ( FIFA 11 + ) to coaches could improve player performance , and to examine the effect of player adherence on performance and injury risk . Method During the 2011 football season ( May – August ) , coaches of 31 tiers 1–3 level teams were introduced to the 11 + through either an unsupervised website or a coach-focused workshop with and without additional on-field supervisions . Playing exposure , adherence to the 11 + , and injuries were recorded for female 13-year-old to 18-year-old players . Performance testing included the Star Excursion Balance Test ( SEBT ) , single-leg balance , triple hop and jumping-over-a-bar tests . Results Complete preseason and postseason performance tests were available for 226 players ( 66.5 % ) . Compared to the unsupervised group , single-leg balance ( OR=2.8 ; 95 % CI 1.1 to 4.6 ) and the anterior direction of the SEBT improved significantly in the onfield supervised group of players ( OR=4.7 ; 95 % CI 2.2 to 7.1 ) , while 2-leg jumping performance decreased ( OR=−5.1 ; 95 % CI −9.9 to −0.2 ) . However , significant improvements in 5 of 6 reach distances in the SEBT were found , favouring players who highly adhered to the 11 + . Also , injury risk was lower for those players ( injury rate ratio , IRR=0.28 , 95 % CI 0.10 to 0.79 ) . Conclusions Different delivery methods of the FIFA 11 + to coaches influenced players ’ physical performance minimally . However , high player adherence to the 11 + result ed in significant improvements in functional balance and reduced injury risk Background Knee injuries in football are common regardless of age , gender or playing level , but adolescent females seem to have the highest risk . The consequences after severe knee injury , for example anterior cruciate ligament ( ACL ) injury , are well-known , but less is known about knee injury prevention . We have design ed a cluster r and omized controlled trial ( RCT ) to evaluate the effect of a warm-up program aim ed at preventing acute knee injury in adolescent female football . Methods In this cluster r and omized trial 516 teams ( 309 clusters ) in eight regional football districts in Sweden with female players aged 13–17 years were r and omized into an intervention group ( 260 teams ) or a control group ( 256 teams ) . The teams in the intervention group were instructed to do a structured warm-up program at two training sessions per week throughout the 2009 competitive season ( April to October ) and those in the control group were informed to train and play as usual . Sixty-eight sports physical therapists are assigned to the clubs to assist both groups in data collection and to examine the players ' acute knee injuries during the study period . Three different forms are used in the trial : ( 1 ) baseline player data form collected at the start of the trial , ( 2 ) computer-based registration form collected every month , on which one of the coaches/team leaders documents individual player exposure , and ( 3 ) injury report form on which the study therapists report acute knee injuries result ing in time loss from training or match play . The primary outcome is the incidence of ACL injury and the secondary outcomes are the incidence of any acute knee injury ( except contusion ) and incidence of severe knee injury ( defined as injury result ing in absence of more than 4 weeks ) . Outcome measures are assessed after the end of the 2009 season . Discussion Prevention of knee injury is beneficial for players , clubs , insurance companies , and society . If the warm-up program is proven to be effective in reducing the incidence of knee injury , it can have a major impact by reducing the future knee injury burden in female football as well as the negative long-term disabilities associated with knee injury . Trial registration Objective To assess the effect of a neuromuscular training program on the incidence of anterior cruciate ligament injuries in female team h and ball players . Design Prospect i ve intervention study . Setting Female team h and ball : Division I – III in Norway . Participants Players from the three top divisions : control season ( 1998–1999 ) , 60 teams ( 942 players ) ; first intervention season ( 1999–2000 ) , 58 teams ( 855 players ) ; second intervention season ( 2000–2001 ) , 52 teams ( 850 players ) . InterventionA five-phase program ( duration , 15 min ) with three different balance exercises focusing on neuromuscular control and planting/l and ing skills was developed and introduced to the players in the autumn of 1999 and revised before the start of the season in 2000 . The teams were instructed in the program and supplied with an instructional video , poster , six balance mats , and six wobble boards . Additionally , a physical therapist was attached to each team to follow up with the intervention program during the second intervention period . Main Outcome Measures The number of anterior cruciate ligament injuries during the three seasons and compliance with the program . Results There were 29 anterior cruciate ligament injuries during the control season , 23 injuries during the first intervention season ( OR , 0.87 ; CI , 0.50–1.52 ; p = 0.62 ) , and 17 injuries during the second intervention season ( OR , 0.64 ; CI , 0.35–1.18 ; p = 0.15 ) . In the elite division , there were 13 injuries during the control season , six injuries during the first intervention season ( OR , 0.51 ; CI , 0.19–1.35 ; p = 0.17 ) , and five injuries in the second intervention season ( OR , 0.37 ; CI , 0.13–1.05 ; p = 0.06 ) . For the entire cohort , there was no difference in injury rates during the second intervention season between those who complied and those who did not comply ( OR , 0.52 ; CI , 0.15–1.82 ; p = 0.31 ) . In the elite division , the risk of injury was reduced among those who completed the anterior cruciate ligament injury prevention program ( OR , 0.06 ; CI , 0.01–0.54 ; p = 0.01 ) compared with those who did not . Conclusions This study shows that it is possible to prevent anterior cruciate ligament injuries with specific neuromuscular training Background This study was conducted to investigate whether the most common injuries in soccer could be prevented , and to determine if a simple question naire could identify players at increased risk . Hypothesis Introduction of targeted exercise programs to male soccer players with a history of previous injury or reduced function in the ankle , knee , hamstring , or groin will prevent injuries . Study Design R and omized controlled trial ; Level of evidence , 2 . Methods A total of 508 players representing 31 teams were included in the study . A question naire indicating previous injury and /or reduced function as inclusion criteria was used to divide the players into high-risk ( HR ) ( 76 % ) and low-risk ( LR ) groups . The HR players were r and omized individually into an HR intervention group or HR control group . Results A total of 505 injuries were reported , sustained by 56 % of the players . The total injury incidence was a mean of 3.2 ( 95 % confidence interval [ CI ] , 2.5–3.9 ) in the LR control group , 5.3 ( 95 % Cl , 4.6–6.0 ) in the HR control group ( P = .0001 vs the LR control group ) , and 4.9 ( 95 % Cl , 4.3–5.6 ) in the HR intervention group ( P = .50 vs the HR control group ) . For the main outcome measure , the sum of injuries to the ankle , knee , hamstring , and groin , there was also a significantly lower injury risk in the LR control group compared with the 2 other groups , but no difference between the HR intervention group and the HR control group . Compliance with the training programs in the HR intervention group was poor , with only 27.5 % in the ankle group , 29.2 % in the knee group , 21.1 % in the hamstring group , and 19.4 % in the groin defined as having carried out the minimum recommended training volume . Conclusion The players with a significantly increased risk of injury were able to be identified through the use of a question naire , but player compliance with the training programs prescribed was low and any effect of the intervention on injury risk could not be detected Abstract . This prospect i ve r and omized intervention investigated whether training on a balance board could reduce the amount of traumatic injuries of the lower extremities in female soccer players . A total of 221 female soccer players from 13 different teams playing in the second and third Swedish divisions volunteered to participate in the study . Seven teams ( n=121 ) were r and omized to an intervention group and six teams ( n=100 ) to a control group and were followed during one outdoor season ( April – October ) . Before and after the season muscle flexibility and balance/postural sway of the lower extremities were measured in the players . There were no significant differences in age , height , weight , muscle flexibility and balance/postural sway of the lower extremities between the intervention and the control group . During the season the players in the intervention group performed a special training program consisting of 10–15 min of balance board training in addition to their st and ard soccer practice and games . After a 37 % drop-out the intervention group consisted of 62 players and the control group of 78 players . The results showed no significant differences between the groups with respect either to the number , incidence , or type of traumatic injuries of the lower extremities . The incidence rate of " major " injuries was higher in the intervention group than in the control group . Four of five anterior cruciate ligament injuries occurred in the intervention group , which means that we could not prevent severe knee injuries in female soccer players with balance board training . However , among the players who had been injured during the 3-month period prior to this investigation there were significantly more players from the control group than from the intervention group who sustained new injuries during the study period Objective To evaluate the effectiveness of neuromuscular training in reducing the rate of acute knee injury in adolescent female football players . Design Stratified cluster r and omised controlled trial with clubs as the unit of r and omisation . Setting 230 Swedish football clubs ( 121 in the intervention group , 109 in the control group ) were followed for one season ( 2009 , seven months ) . Participants 4564 players aged 12 - 17 years ( 2479 in the intervention group , 2085 in the control group ) completed the study . Intervention 15 minute neuromuscular warm-up programme ( targeting core stability , balance , and proper knee alignment ) to be carried out twice a week throughout the season . Main outcome measures The primary outcome was rate of anterior cruciate ligament injury ; secondary outcomes were rates of severe knee injury ( > 4 weeks ’ absence ) and any acute knee injury . Results Seven players ( 0.28 % ) in the intervention group , and 14 ( 0.67 % ) in the control group had an anterior cruciate ligament injury . By Cox regression analysis according to intention to treat , a 64 % reduction in the rate of anterior cruciate ligament injury was seen in the intervention group ( rate ratio 0.36 , 95 % confidence interval 0.15 to 0.85 ) . The absolute rate difference was −0.07 ( 95 % confidence interval −0.13 to 0.001 ) per 1000 playing hours in favour of the intervention group . No significant rate reductions were seen for secondary outcomes . Conclusions A neuromuscular warm-up programme significantly reduced the rate of anterior cruciate ligament injury in adolescent female football players . However , the absolute rate difference did not reach statistical significance , possibly owing to the small number of events . Trial registration Clinical trials NCT00894595 Background A recent study published in The American Journal of Sports Medicine showed that asymptomatic soccer players with an increased risk of developing Achilles and patellar tendon injuries within the next 12 months can be identified with use of ultrasonography . Hypothesis Pro Output:	The RE- AIM MDIC can be successfully applied to review ing literature in this context
MS21229	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Interferon alfa and cytotoxic drugs have synergistic effects in patients with non-Hodgkin 's lymphoma . In 1986 , we design ed a clinical trial to evaluate the benefit of concomitant administration of recombinant interferon alfa with a regimen containing doxorubicin in patients with follicular non-Hodgkin 's lymphoma . METHODS The trial involved 242 patients with advanced low- grade follicular non-Hodgkin 's lymphoma selected on the basis of clinical , radiographic , and biologic criteria . All patients were treated with a regimen consisting of cyclophosphamide , doxorubicin , teniposide , and prednisone ( CHVP ) , given monthly for six cycles and then every two months for one year . After r and omization , 123 patients also received interferon alfa-2b at a dosage of 5 million units three times weekly for 18 months . The remaining 119 patients received chemotherapy alone . RESULTS As compared with the patients treated with CHVP only , the patients treated with CHVP plus interferon alfa had a higher overall rate of response ( 85 percent vs. 69 percent , P = 0.006 ) , a longer median event-free survival ( 34 months vs. 19 months , P < 0.001 ) , and a higher rate of survival at 3 years ( 86 percent vs. 69 percent , P = 0.02 ) . Granulocyte toxicity was greater in the patients treated with CHVP plus interferon alfa than in those treated with CHVP alone . There were no treatment-related deaths . Interferon alfa had to be stopped because of toxic effects ( fatigue and hepatitis ) in 13 patients ( 11 percent ) . CONCLUSIONS The addition of interferon alfa to a regimen containing doxorubicin increased the rate of response , event-free survival , and overall survival in patients with advanced follicular non-Hodgkin 's lymphoma , without serious toxicity , although some patients were unable to tolerate the side effects A total of 296 evaluable patients with unfavorable categories of malignant lymphoma were r and omly assigned treatment with cyclophosphamide , vincristine , and prednisone plus BCNU ( BCOP ) or doxorubicin ( CHOP ) . In diffuse histiocytic ( DH ) lymphoma , CHOP produced superior complete ( 54 % v 34 % ) and total ( 70 % v 46 % ) response rates . Among the responders to either therapy , no differences were seen in duration of response or survival times . Median duration of response has not been reached with follow-up in excess of 50 months . In categories of lymphoma other than DH ( including small-cell , mixed , and nodular histiocytic lymphomas ) , complete ( 27 % v 29 % ) and total ( 48 % v 54 % ) responses were similar for BCOP and CHOP , as were duration s of response and survival . These data suggest that BCOP and CHOP are equivalent regimens for other categories of malignant lymphomas . CHOP appears preferable for diffuse large-cell categories , since it result ed in greater overall survival in patients with DH lymphoma ; this was due to a significantly greater response rate , since patients with DH lymphoma who did respond to BCOP maintained their response and survived as long as did the CHOP responders PURPOSE The aim of the F2 study was to verify whether a prospect i ve collection of data would enable the development of a more accurate prognostic index for follicular lymphoma ( FL ) by using parameters which could not be retrospectively studied before , and by choosing progression-free survival ( PFS ) as principal end point . PATIENTS AND METHODS Between January 2003 and May 2005 , 1,093 patients with a newly diagnosed FL were registered and 942 individuals receiving antilymphoma therapy were selected as the study population . The variables we used for score definition were selected by means of bootstrap resampling procedures on 832 patients with complete data . Procedures to select the model that would minimize errors were also performed . RESULTS After a median follow-up of 38 months , 261 events for PFS evaluation were recorded . beta2-microglobulin higher than the upper limit of normal , longest diameter of the largest involved node longer than 6 cm , bone marrow involvement , hemoglobin level lower than 12 g/dL , and age older than 60 years were factors independently predictive for PFS . Using these variables , a prognostic model was devised to identify three groups at different levels of risk . The 3-year PFS rate was 91 % , 69 % , and 51 % for patients at low , intermediate , and high risk , respectively ( log-rank = 64.6 ; P < .00001 ) . The 3-year survival rate was 99 % , 96 % , and 84 % for patients at low , intermediate , and high risk , respectively ( P < .0001 ) . CONCLUSION Follicular Lymphoma International Prognostic Index 2 is a simple prognostic index based on easily available clinical data and may represent a promising new tool for the identification of patients with FL at different risk in the era of immunochemotherapy Between July 1 , 1971 and December 31 , 1978 , 150 patients with favorable subtypes of non-Hodgkin 's lymphoma [ nodular poorly differentiated lymphocytic ( NLPD ) , nodular mixed , or diffuse well differentiated lymphocytic ] were entered into prospect i ve r and omized clinical trials at Stanford University . Treatments included involved field , total lymphoid , or whole body irradiation , single alkylating agent chemotherapy , combination chemotherapy with cyclophosphamide , vincristine and prednisone ( CVP ) or with cyclophosphamide , vincristine , procarbazine , and prednisone ( C-MOPP ) , or various combinations of chemotherapy and irradiation . The initial complete response rate ( CR ) was 79 % . Among patients who achieved a CR , 31 % later relapsed . There were 78 patients who either failed to achieve a CR or achieved a CR and later relapsed . Histologic conversion ( change from initially favorable to an unfavorable subtype of non-Hodgkin 's lymphoma ) was documented in 22/78 patients ( 28 % ) . However , the actuarial risk for conversion was actually much greater ( 60 % at 8 yr ) . The median time to documentation of conversion was 51 mo . The most common type of histologic conversion was from NLPD to diffuse histiocytic lymphoma . Documented histologic conversion was often associated with a more aggressive clinical behavior of the lymphoma , and the median survival after conversion was less than 1 yr . However , those patients who achieved a CR after conversion had a more favorable outcome ( actuarial survival 75 % at 5 yr ) . No specific risk factors predictive of histologic conversion could be identified One hundred patients with untreated non-Hodgkin 's lymphoma were entered in a prospect i ve r and omized study in South and West Wales design ed to assess the value of the anthracycline antibiotic , epirubicin ( 4'-epidoxorubicin ) , in their management . Patients with low grade histology and progressive disease were r and omized to receive either epirubicin , vincristine and prednisolone ( EVP ) or cyclophosphamide , vincristine and prednisolone ( CVP ) . The response rate of 81 % in patients receiving EVP with complete remission rate of 52 % were similar to a response rate of 88 % and complete remission rate of 58 % for patients receiving CVP . No difference was observed in survival between the two groups . Patients with high grade lymphoma were r and omized to receive either cyclophosphamide , doxorubicin , vincristine and prednisolone ( CHOP ) or cyclophosphamide , epirubicin , vincristine and prednisolone ( CEOP ) . The response rate was 71 % for CHOP and 84 % for CEOP . The complete remission rates were 46 % for CHOP and 61 % for CEOP . The cardiotoxicity of the two anthracyclines were monitored closely in 45 patients using measurements of systolic time intervals . Patients receiving epirubicin tolerated higher dose per course and higher total cumulative dose with less evidence of compromised left ventricular function than patients receiving doxorubicin . Epirubicin is an effective agent when used in combination chemotherapy in both low grade and high grade lymphoma with less toxicity than doxorubicin PURPOSE Advanced-stage follicular lymphoma is considered incurable . The pace of improvements in treatment has been slow . This article analyzes five sequential cohorts of patients with stage IV follicular lymphoma treated between 1972 and 2002 . METHODS Five consecutive studies ( two were r and omized trials ) involving 580 patients were analyzed for overall survival ( OS ) , failure-free survival ( FFS ) , and survival after first relapse . A proportional hazards analysis , and subset analyses using the follicular lymphoma international prognostic index ( FLIPI ) score were performed . Treatment regimens included : cyclophosphamide , doxorubicin , vincristine , prednisone , bleomycin ( CHOP-Bleo ) ; CHOP-Bleo followed by interferon alfa ( IFN-alpha ) ; a rotation of three regimens ( alternating triple therapy ) , followed by IFN-alpha ; fludarabine , mitoxantrone , dexamethasone ( FND ) followed by IFN-alpha ; and FND plus delayed versus concurrent rituximab followed by IFN-alpha . RESULTS Improvements in 5-year OS ( from 64 % to 95 % ) and FFS ( from 29 % to 60 % ) indicate steady progress , perhaps partly due to more effective salvage therapies , but the FFS data also indicate improved front-line therapies ; these observations held true after controlling for differences in prognostic factors among the cohorts . The FLIPI model adds rigor to and facilitates comparisons among the different cohorts . An unexpected finding in this study was a trend toward an apparent FFS plateau . CONCLUSION Evolving therapy , including the incorporation of biologic agents , has led to stepwise significant outcome improvements for patients with advanced-stage follicular lymphoma . The apparent plateau in the FFS curve , starting approximately 8 to 10 years from the beginning of treatment , raises the issue of the potential curability of these patients The recognition of several new types of non-Hodgkin 's lymphoma ( NHL ) in recent years has led to proposals for changing lymphoma classifications , including a new proposal put forth by the International Lymphoma Study Group ( ILSG ) . However , the clinical significance of the new entities and the practical utility of this new proposal have not been studied . Therefore , we performed a clinical evaluation of the ILSG classification . A cohort of 1,403 cases of NHL was organized at nine study sites around the world and consisted of consecutive patients seen between 1988 and 1990 who were previously untreated . A detailed protocol for histologic and clinical analysis was followed at each site , and immunologic characterization as to T- or B-cell phenotype was required . Five expert hematopathologists visited the sites and each classified each case using the ILSG classification . A consensus diagnosis was also reached in each case , and each expert re review ed a 20 % r and om sample of the cases . Clinical correlations and survival analyses were then performed . A diagnosis of NHL was confirmed in 1,378 ( 98.2 % ) of the cases . The most common lymphoma types were diffuse large B-cell lymphoma ( 31 % ) and follicular lymphoma ( 22 % ) , whereas the new entities comprised 21 % of the cases . Diagnostic accuracy was at least 85 % for most of the major lymphoma types , and reproducibility of the diagnosis was 85 % . Immunophenotyping improved the diagnostic accuracy by 10 % to 45 % for a number of the major types . The clinical features of the new entities were distinctive . Both the histologic types and the patient characteristics as defined by the International Prognostic Index predicted for patient survival . In conclusion we found that the ILSG classification can be readily applied and identifies clinical ly distinctive types of NHL . However , for clinical application , prognostic factors as defined by the International Prognostic Index must be combined with the histologic diagnosis for appropriate clinical decisions Background . In a prospect i ve r and omized manner , this study evaluated the effect of adjuvant chemotherapy ( cyclophosphamide , doxorubicin , vincristine , and prednisone ; CHOP ) in patients with Stage I non‐Hodgkin lymphoma ( NHL ) who have achieved a complete response ( CR ) after radiation therapy ( RT ) PURPOSE Although rituximab ( R ) is commonly used for patients with advanced follicular lymphoma ( FL ) requiring treatment , the optimal associated chemotherapy regimen has yet to be clarified . PATIENTS AND METHODS We conducted an open-label , multicenter , r and omized trial among adult patients with previously untreated stages II to IV FL to compare efficacy of eight doses of R associated with eight cycles of cyclophosphamide , vincristine , and prednisone ( CVP ) or six cycles of cyclophosphamide , doxorubicin , vincristine , and prednisone ( CHOP ) or six cycles of fludarabine and mitoxantrone ( FM ) . The principal end point of the study was time to treatment failure ( TTF ) . RESULTS There were 534 patients enrolled onto the study Output:	None showed benefit to ACR regarding OS , yet there was a trend in favor of anthracyclines for disease control . ACR improved disease control , as measured by PFS and RD with an increased risk for side effects , notably cardiotoxicity .
MS21230	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Purpose The purpose of this study was to compare the efficacy of intravitreal aflibercept and ranibizumab in the treatment of diabetic macular edema ( DME ) in eyes with moderate visual loss . Patients and methods This study is a r and omized prospect i ve study . Seventy eyes with DME were divided into two groups ( each containing 35 eyes ) . Eyes in group I were treated with intravitreal injection of 2 mg/0.05 mL aflibercept and eyes in group II were treated with intravitreal injection of 0.5 mg/0.1 mL ranibizumab . All the eyes had three successive injections as a loading dose ( with 1 month interval ) , and then the patients were followed up monthly for 12 months . The outcomes of the study were visual acuity , central macular thickness ( CMT ) , and the number of re-injections of the drug . Results Mean age of the patients in group I was 55.05±4.7 years and in group II was 56.64±5.8 years ( P=0.17 ) . The mean baseline best corrected visual acuity ( BCVA ) of eyes treated with aflibercept was 0.17±0.05 and with ranibizumab was 0.18±0.04 ( P=0.9 ) . BCVA was improved in both the groups at the end of the follow-up period and was found to be 0.42±0.28 and 0.37±0.23 , respectively ( P=0.27 ) . The mean baseline CMT of eyes in group I was 465.29±33.7 µm and in group II was 471.5±34.4 µm ( P=0.65 ) . CMT decreased in both the groups to 360.8±85.7 µm and 387.3±87.8 µm , respectively ( P=0.2 ) . The mean number of drug re-injection was 2.62±0.68 and 3.03±0.95 in both the groups , respectively ( P=0.02 ) . Conclusion Aflibercept and ranibizumab have the same efficacy in the treatment of DME in eyes with moderate visual loss but with less number of drug re-injection and less treatment burden with aflibercept ( 2.62±0.68 versus 3.03±0.95 ) Purpose To report 1-year visual and anatomic outcomes of a prospect i ve , double-masked r and omised clinical trial comparing bevacizumab with ranibizumab for the treatment of age-related macular degeneration ( AMD ) . Methods Patients who met inclusion criteria were r and omised 2 : 1 to bevacizumab or ranibizumab . All subjects and investigators ( except for the pharmacist responsible for study assignments ) were masked to treatment arms . Visual acuity was taken on Early Treatment Diabetic Retinopathy Study chart . Patients were given either bevacizumab or ranibizumab every month for the first 3 months , followed by an optical coherence tomography-guided , variable-dosing treatment schedule . Main outcomes measured included visual acuity , foveal thickness , and total number of injections over the 1-year treatment period . Results In total , 15 patients received bevacizumab and 7 patients received ranibizumab . The average pre-operative visual acuity was 34.9 letters in the bevacizumab group , and 32.7 letters in the ranibizumab group . At 1-year follow-up , mean vision was 42.5 letters in the bevacizumab group , and 39.0 letters in the ranibizumab group . Two-tailed t-test failed to showed statistical significance between the two groups ( P=0.5 ) . Patients in the bevacizumab group underwent an average of eight injections , whereas patients in the ranibizumab group underwent a mean of four injections ( P=0.001 ) . Conclusion The 1-year outcomes of a prospect i ve , double-masked , r and omised clinical trial comparing bevacizumab with ranibizumab failed to show a difference in visual and anatomic outcomes between the two treatments for choroidal neovascularisation in AMD . Total injections given over the treatment period were significantly different between the two groups . Further studies with larger sample sizes are warranted OBJECTIVE Two similarly design ed , phase-3 studies ( VEGF Trap-Eye : Investigation of Efficacy and Safety in Wet AMD [ VIEW 1 , VIEW 2 ] ) of neovascular age-related macular degeneration ( AMD ) compared monthly and every-2-month dosing of intravitreal aflibercept injection ( VEGF Trap-Eye ; Regeneron , Tarrytown , NY , and Bayer HealthCare , Berlin , Germany ) with monthly ranibizumab . DESIGN Double-masked , multicenter , parallel-group , active-controlled , r and omized trials . PARTICIPANTS Patients ( n = 2419 ) with active , subfoveal , choroidal neovascularization ( CNV ) lesions ( or juxtafoveal lesions with leakage affecting the fovea ) secondary to AMD . INTERVENTION Patients were r and omized to intravitreal aflibercept 0.5 mg monthly ( 0.5q4 ) , 2 mg monthly ( 2q4 ) , 2 mg every 2 months after 3 initial monthly doses ( 2q8 ) , or ranibizumab 0.5 mg monthly ( Rq4 ) . MAIN OUTCOME MEASURES The primary end point was noninferiority ( margin of 10 % ) of the aflibercept regimens to ranibizumab in the proportion of patients maintaining vision at week 52 ( losing < 15 letters on Early Treatment Diabetic Retinopathy Study [ ETDRS ] chart ) . Other key end points included change in best-corrected visual acuity ( BCVA ) and anatomic measures . RESULTS All aflibercept groups were noninferior and clinical ly equivalent to monthly ranibizumab for the primary end point ( the 2q4 , 0.5q4 , and 2q8 regimens were 95.1 % , 95.9 % , and 95.1 % , respectively , for VIEW 1 , and 95.6 % , 96.3 % , and 95.6 % , respectively , for VIEW 2 , whereas monthly ranibizumab was 94.4 % in both studies ) . In a prespecified integrated analysis of the 2 studies , all aflibercept regimens were within 0.5 letters of the reference ranibizumab for mean change in BCVA ; all aflibercept regimens also produced similar improvements in anatomic measures . Ocular and systemic adverse events were similar across treatment groups . CONCLUSIONS Intravitreal aflibercept dosed monthly or every 2 months after 3 initial monthly doses produced similar efficacy and safety outcomes as monthly ranibizumab . These studies demonstrate that aflibercept is an effective treatment for AMD , with the every-2-month regimen offering the potential to reduce the risk from monthly intravitreal injections and the burden of monthly monitoring . FINANCIAL DISCLOSURE(S ) Proprietary or commercial disclosure may be found after the references PURPOSE To compare efficacy and safety of intravitreal aflibercept injection ( IAI ) with macular laser photocoagulation for diabetic macular edema ( DME ) over 3 years . DESIGN Two similarly design ed phase 3 trials : VISTADME and VIVIDDME . PARTICIPANTS Patients ( eyes ; n = 872 ) with central -involved DME . METHODS Eyes received IAI 2 mg every 4 weeks ( 2q4 ) , IAI 2 mg every 8 weeks after 5 monthly doses ( 2q8 ) , or laser control . From week 24 , if rescue treatment criteria were met , IAI patients received active laser , and laser control patients received IAI 2q8 . From week 100 , laser control patients who had not received IAI rescue treatment received IAI as needed per retreatment criteria . MAIN OUTCOME MEASURES The primary end point was the change from baseline in best-corrected visual acuity ( BCVA ) at week 52 . We report the 148-week results . RESULTS Mean BCVA gain from baseline to week 148 with IAI 2q4 , IAI 2q8 , and laser control was 10.4 , 10.5 , and 1.4 letters ( P < 0.0001 ) in VISTA and 10.3 , 11.7 , and 1.6 letters ( P < 0.0001 ) in VIVID , respectively . The proportion of eyes that gained ≥15 letters from baseline at week 148 was 42.9 % , 35.8 % , and 13.6 % ( P < 0.0001 ) in VISTA and 41.2 % , 42.2 % , and 18.9 % ( P < 0.0001 ) in VIVID , respectively . Greater proportions of eyes treated with IAI 2q4 and IAI 2q8 versus those treated with laser control had an improvement of ≥2 steps in the Diabetic Retinopathy Severity Scale ( DRSS ) score in both VISTA ( 29.9 % and 34.4 % vs. 20.1 % [ P = 0.0350 , IAI 2q4 ; P = 0.0052 , IAI 2q8 ] ) and VIVID ( 44.3 % and 47.8 % vs. 17.4 % [ P < 0.0001 for both ] ) . In an integrated safety analysis , the most frequent ocular serious adverse event was cataract ( 3.1 % , 2.1 % , 0.3 % for 2q4 , 2q8 , and control ) . CONCLUSIONS Visual improvements observed with both IAI regimens ( over laser control ) at weeks 52 and 100 were maintained at week 148 , with similar overall efficacy in the IAI 2q4 and IAI 2q8 groups . Treatment with IAI also had positive effects on the DRSS score . Over 148 weeks , the incidence of adverse events was consistent with the known safety profile of IAI PURPOSE To provide 2-year results comparing anti-vascular endothelial growth factor ( VEGF ) agents for center-involved diabetic macular edema ( DME ) using a st and ardized follow-up and retreatment regimen . DESIGN R and omized clinical trial . PARTICIPANTS Six hundred sixty participants with visual acuity ( VA ) impairment from DME . METHODS R and omization to 2.0-mg aflibercept , 1.25-mg repackaged ( compounded ) bevacizumab , or 0.3-mg ranibizumab intravitreous injections performed up to monthly using a protocol -specific follow-up and retreatment regimen . Focal/grid laser photocoagulation was added after 6 months if DME persisted . Visits occurred every 4 weeks during year 1 and were extended up to every 4 months thereafter when VA and macular thickness were stable . MAIN OUTCOME MEASURES Change in VA , adverse events , and retreatment frequency . RESULTS Median numbers of injections were 5 , 6 , and 6 in year 2 and 15 , 16 , and 15 over 2 years in the aflibercept , bevacizumab , and ranibizumab groups , respectively ( global P = 0.08 ) . Focal/grid laser photocoagulation was administered in 41 % , 64 % , and 52 % , respectively ( aflibercept vs. bevacizumab , P < 0.001 ; aflibercept vs. ranibizumab , P = 0.04 ; bevacizumab vs. ranibizumab , P = 0.01 ) . At 2 years , mean VA improved by 12.8 , 10.0 , and 12.3 letters , respectively . Treatment group differences varied by baseline VA ( P = 0.02 for interaction ) . With worse baseline VA ( 20/50 to 20/320 ) , mean improvement was 18.1 , 13.3 , and 16.1 letters , respectively ( aflibercept vs. bevacizumab , P = 0.02 ; aflibercept vs. ranibizumab , P = 0.18 ; ranibizumab vs. bevacizumab , P = 0.18 ) . With better baseline VA ( 20/32 to 20/40 ) , mean improvement was 7.8 , 6.8 , and 8.6 letters , respectively ( P > 0.10 , for pairwise comparisons ) . Anti-Platelet Trialists ' Collaboration ( APTC ) events occurred in 5 % with aflibercept , 8 % with bevacizumab , and 12 % with ranibizumab ( global P = 0.047 ; aflibercept vs. bevacizumab , P = 0.34 ; aflibercept vs. ranibizumab , P = 0.047 ; ranibizumab vs. bevacizumab , P = 0.20 ; global P = 0.09 adjusted for potential confounders ) . CONCLUSIONS All 3 anti-VEGF groups showed VA improvement from baseline to 2 years with a decreased number of injections in year 2 . Visual acuity outcomes were similar for eyes Output:	Similarly , vision gain was not significantly different between cn-AMD patients treated with aflibercept versus ranibizumab . Rates of systemic serious harms were similar across anti-VEGF agents . Intravitreal bevacizumab was a reasonable alternative to ranibizumab and aflibercept in patients with cn-AMD , DMO , RVO-MO and m-CNV . The only exception was for patients with DME and low visual acuity ( < 69 early treatment diabetic retinopathy study [ ETDRS ] letters ) , where treatment with aflibercept was associated with significantly higher vision gain ( ≥15 ETDRS letters ) than bevacizumab or ranibizumab at 12 months ; but the significant effects were not maintained at 24 months .
MS21231	*TASK* the task is to summarize an input biomedical literature in six sentences *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 growing number of empirical studies have revealed that diaphragmatic breathing may trigger body relaxation responses and benefit both physical and mental health . However , the specific benefits of diaphragmatic breathing on mental health remain largely unknown . The present study aim ed to investigate the effect of diaphragmatic breathing on cognition , affect , and cortisol responses to stress . Forty participants were r and omly assigned to either a breathing intervention group ( BIG ) or a control group ( CG ) . The BIG received intensive training for 20 sessions , implemented over 8 weeks , employing a real-time feedback device , and an average respiratory rate of 4 breaths/min , while the CG did not receive this treatment . All participants completed pre- and post-tests of sustained attention and affect . Additionally , pre-test and post-test salivary cortisol concentrations were determined in both groups . The findings suggested that the BIG showed a significant decrease in negative affect after intervention , compared to baseline . In the diaphragmatic breathing condition , there was a significant interaction effect of group by time on sustained attention , whereby the BIG showed significantly increased sustained attention after training , compared to baseline . There was a significant interaction effect of group and time in the diaphragmatic breathing condition on cortisol levels , whereby the BIG had a significantly lower cortisol level after training , while the CG showed no significant change in cortisol levels . In conclusion , diaphragmatic breathing could improve sustained attention , affect , and cortisol levels . This study provided evidence demonstrating the effect of diaphragmatic breathing , a mind-body practice , on mental function , from a health psychology approach , which has important implication s for health promotion in healthy individuals BACKGROUND Among non-pharmacological therapies , musical intervention is often used for patients with Alzheimer 's disease ( AD ) and patients presenting chronic pain . However , their efficacy is still under debate . OBJECTIVE Our aim was to determine the efficacy of choral singing versus painting sessions on chronic pain , mood , quality of life , and cognition in AD patients . METHODS In this multicenter r and omized controlled trial , 59 mild AD patients were r and omized to a 12-week singing ( SG ; n = 31 ) or painting group ( PG ; n = 28 ) . Chronic pain , anxiety , depression , and quality of life were assessed before , after , and 1 month after the sessions . Cognitive abilities were assessed before and after interventions . The evolution of these different measures was assessed with mixed linear models . The primary data analysis was by intention-to-treat , and completed by a ' per protocol ' approach . RESULTS Both singing and painting interventions led to significant pain reduction ( Time effect : F = 4.71 ; p = 0.01 ) , reduced anxiety ( Time effect : F = 10.74 ; p < 0.0001 ) , improved Quality of Life ( Time effect : F = 6.79 ; p = 0.002 ) , improved digit span ( F = 12.93 ; p = 0.001 ) , and inhibitory processes ( Time effect : F = 4.93 ; p = 0.03 ) . Depression was reduced over time in PG only ( Time x Group effect : F = 4.53 ; p = 0.01 ) . Verbal Memory performance remained stable over time in SG , but decreased in PG ( Time x group effect : F = 9.29 ; p = 0.004 ) . CONCLUSION Findings suggest that singing and painting interventions may reduce pain and improve mood , quality of life , and cognition in patients with mild AD , with differential effects of painting for depression and singing for memory performance This study aim ed to investigate the effects of weekly singings classes on pulmonary function parameters and quality of life ( QoL ) of COPD patients . Forty-three patients were r and omized to weekly classes of singing practice , or h and craft work . They performed spirometry and completed maximal respiratory pressure measurements , evaluations of dyspnea , and the Saint George ’s Respiratory Question naire , before and after 24 training classes . A functional evaluation , immediately after 10 minutes of singing practice , was also performed at the end of the study . Fifteen subjects completed the study in each group . In comparison to controls the singing group exhibited transitory elevations on the dyspnea Borg scale ( p = 0.02 ) , and inspiratory capacity ( p = 0.01 ) , and decreases of expiratory reserve volume ( p = 0.03 ) , just after a short session of singing . There was a significant difference on changes of maximal expiratory pressures in the comparison between groups at the end of training . While the control group showed deterioration of maximal expiratory pressure , the singing group exhibited a small improvement ( p = 0.05 ) . Both groups showed significant improvements of QoL in within group comparisons . We have concluded that singing classes are a well tolerated activity for selected subjects with COPD . Regular practice of singing may improve QoL , and preserve the maximal expiratory pressure of these patients Background There is some evidence that singing lessons may be of benefit to patients with chronic obstructive pulmonary disease ( COPD ) . It is not clear how much of this benefit is specific to singing and how much relates to the classes being a group activity that addresses social isolation . Methods Patients were r and omised to either singing classes or a film club for eight weeks . Response was assessed quantitatively through health status question naires , measures of breathing control , exercise capacity and physical activity and qualitatively , through structured interviews with a clinical psychologist . Results The singing group ( n=13 mean(SD ) FEV1 44.4(14.4)% predicted ) and film group ( n=11 FEV1 63.5(25.5)%predicted ) did not differ significantly at baseline . There was a significant difference between the response of the physical component score of the SF-36 , favouring the singing group + 12.9(19.0 ) vs -0.25(11.9 ) ( p=0.02 ) , but no difference in response of the mental component score of the SF-36 , breathing control measures , exercise capacity or daily physical activity . In the qualitative element , positive effects on physical well-being were reported in the singing group but not the film group . ConclusionS inging classes have an impact on health status distinct from that achieved simply by taking part in a group activity . Trials registration Registration Current Controlled Trials - IS RCT Background Despite optimal pharmacological therapy and pulmonary rehabilitation , patients with COPD continue to be breathless . There is a need to develop additional strategies to alleviate symptoms . Learning to sing requires control of breathing and posture and might have benefits that translate into daily life . Methods To test this hypothesis we performed a r and omised controlled trial , comparing a six week course of twice weekly singing classes to usual care , in 28 COPD patients . The experience of singing was assessed in a qualitative fashion , through interviews with a psychologist . In addition , we surveyed patients with chronic respiratory conditions who participated in a series of open singing workshops . Results In the RCT , the physical component score of the SF36 improved in the singers ( n = 15 ) compared to the controls ( n = 13 ) ; + 7.5(14.6 ) vs. -3.8(8.4 ) p = 0.02 . Singers also had a significant fall in HAD anxiety score ; -1.1(2.7 ) vs. + 0.8(1.7 ) p = 0.03 . Singing did not improve single breath counting , breath hold time or shuttle walk distance . In the qualitative element , 8 patients from the singing group were interviewed . Positive effects on physical sensation , general well-being , community/social support and achievement/efficacy emerged as common themes . 150 participants in open workshops completed a question naire . 96 % rated the workshops as " very enjoyable " and 98 % thought the workshop had taught them something about breathing in a different way . 81 % of attendees felt a " marked physical difference " after the workshop . ConclusionS inging classes can improve quality of life measures and anxiety and are viewed as a very positive experience by patients with respiratory disease ; no adverse consequences of participation were observed . Trial Registration Current Controlled Trials - IS RCT N17544114 Objective The purpose of this experimental study was to supplement and exp and on clinical research demonstrating that the provision of social support is associated with lower levels of acute pain . Methods Undergraduates ( 52 men and 49 women ) performed the cold pressor task either alone or accompanied by a friend or stranger who provided active support , passive support , or interaction . Pain perception was measured on a 10-point scale . Results Participants in the active support and passive support conditions reported less pain than participants in the alone and interaction conditions , regardless of whether they were paired with a friend or stranger . Conclusions These data suggest that the presence of an individual who provides passive or active support reduces experimental pain OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity This study explored the impact of group singing on mood , coping , and perceived pain in chronic pain patients attending a multidisciplinary pain clinic . Singers participated in nine 30-minute sessions of small group singing , while comparisons listened to music while exercising . A short form of The Profile of Mood States ( POMS ) was administered before and after selected singing sessions to assess whether singing produced short-term elevations in mood . Results indicated that pre to post difference scores were significantly different between singing and control groups for only one of the 15 mood variables ( i.e. , uneasy ) . To test the longer term impacts of singing the Profile of Mood States , Zung Depression Inventory , Pain Self-Efficacy Question naire , Pain Rating Self-Statement , and Pain Disability Question naire were administered immediately before and after the singing sessions . All inventories other than the POMS were re-administered 6 months later . One-way ANCOVAs indicated that participants who attended the singing sessions showed evidence of postintervention improvements in active coping , relative to those who failed to attend , when preintervention differences in active coping were controlled for . While the singing group showed marked improvements from pre to postintervention on all mood , coping , and perceived pain variables , these improvements were also observed among comparison participants . The results of this study suggest that active singing may have some benefits , in terms of enhancing active coping , though the limitations of the study and small effect sizes observed suggest that further research is required to fully explore such effects OBJECTIVE Deep and slow breathing ( DSB ) techniques , as a component of various relaxation techniques , have been reported as complementary approaches in the treatment of chronic pain syndromes , but the relevance of relaxation for alleviating pain during a breathing intervention was not evaluated so far . METHODS In order to disentangle the effects of relaxation and respiration , we investigated two different DSB techniques at the same respiration rates and depths on pain perception , autonomic activity , and mood in 16 healthy subjects . In the attentive DSB intervention , subjects were asked to breathe guided by a respiratory feedback task requiring a high degree of concentration and constant attention . In the relaxing DSB intervention , the subjects relaxed during the breathing training . The skin conductance levels , indicating sympathetic tone , were measured during the breathing maneuvers . Thermal detection and pain thresholds for cold and hot stimuli and profile of mood states were examined before and after the breathing sessions . RESULTS The mean detection and pain thresholds showed a significant increase result ing from the relaxing DSB , whereas no significant changes of these thresholds were found associated with the attentive DSB . The mean skin conductance levels indicating sympathetic activity decreased significantly during the relaxing DSB intervention but not during the attentive DSB . Both breathing interventions showed similar reductions in negative feelings ( tension , anger , and depression ) . CONCLUSION Our results suggest that the way of breathing decisively influences autonomic and pain processing , thereby identifying DSB in concert with relaxation as the essential feature in the modulation of sympathetic arousal and pain perception Current evidence suggests that participatory arts activities , and particularly group singing , may contribute to the well-being of older people . However , there is currently a paucity of prospect i ve research from Output:	There is a positive trend of singing interventions reducing pain intensity , but more equivocal support for reductions in pain interference and depression . Group singing appears to have potential to reduce pain intensity , pain interference and depression ; however , we conclude there is only partial support for singing on some pain outcomes based on the limited available evidence of varied quality . Group singing may be an effective and safe approach for reducing persistent pain and depression in people with long-term health conditions
MS21232	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Abstract Variability in patients ' response to interventions in pain and other clinical setting s is large . Many explanations such as trial methods , environment or culture have been proposed , but this paper sets out to show that the main cause of the variability may be r and om chance , and that if trials are small their estimate of magnitude of effect may be incorrect , simply because of the r and om play of chance . This is highly relevant to the questions of ‘ How large do trials have to be for statistical accuracy ? ’ and ‘ How large do trials have to be for their results to be clinical ly valid ? ’ The true underlying control event rate ( CER ) and experimental event rate ( EER ) were determined from single‐dose acute pain analgesic trials in over 5000 patients . Trial group size required to obtain statistically significant and clinical ly relevant ( 0.95 probability of number‐needed‐to‐treat within ±0.5 of its true value ) results were computed using these values . Ten thous and trials using these CER and EER values were simulated using varying group sizes to investigate the variation due to r and om chance alone . Most common analgesics have EERs in the range 0.4–0.6 and CER of about 0.19 . With such efficacy , to have a 90 % chance of obtaining a statistically significant result in the correct direction requires group sizes in the range 30–60 . For clinical relevance nearly 500 patients are required in each group . Only with an extremely effective drug ( EER>0.8 ) will we be reasonably sure of obtaining a clinical ly relevant NNT with commonly used group sizes of around 40 patients per treatment arm . The simulated trials showed substantial variation in CER and EER , with the probability of obtaining the correct values improving as group size increased . We contend that much of the variability in control and experimental event rates is due to r and om chance alone . Single small trials are unlikely to be correct . If we want to be sure of getting correct ( clinical ly relevant ) results in clinical trials we must study more patients . Credible estimates of clinical efficacy are only likely to come from large trials or from pooling multiple trials of conventional ( small ) size Background Differences between gastrointestinal and cardiovascular effects of traditional NSAID or cyclooxygenase-2 selective inhibitor ( coxib ) are affected by drug , dose , duration , outcome definition , and patient gastrointestinal and cardiovascular risk factors . We calculated the absolute risk for each effect . Methods We sought studies with large amounts of information to calculate annualised rates for clearly defined gastrointestinal ( complicated upper gastrointestinal perforations , ulcers , or bleeds , but not symptomatic or endoscopic ulcers ) and serious cardiovascular outcomes ( antiplatelet trial collaborators – APTC – outcome of fatal or nonfatal myocardial infa rct ion or stroke , or vascular death ) . Results Meta-analyses and large r and omised trials specifically analysing serious gastrointestinal bleeding or cardiovascular events occurring with five different coxibs had appropriate data . In total there were 439 complicated upper gastrointestinal events in 49,006 patient years of exposure and 948 serious cardiovascular events in 99,400 patient years of exposure . Complicated gastrointestinal events occurred less frequently with coxibs than NSAIDs ; serious cardiovascular events occurred at approximately equal rates . For each coxib , the reduction in complicated upper gastrointestinal events was numerically greater than any increase in APTC events . In the overall comparison , for every 1000 patients treated for a year with coxib rather than NSAID , there would be eight fewer complicated upper gastrointestinal events , but one more fatal or nonfatal heart attack or stroke . Three coxib-NSAID comparisons had sufficient numbers of events for individual comparisons . For every 1000 patients treated for a year with celecoxib rather than an NSAID there would be 12 fewer upper gastrointestinal complications , and two fewer fatal or nonfatal heart attacks or strokes . For rofecoxib there would be six fewer upper gastrointestinal complications , but three more fatal or nonfatal heart attacks or strokes . For lumiracoxib there would be eight fewer upper gastrointestinal complications , but one more fatal or nonfatal heart attack or stroke . Conclusion Calculating annualised event rates for gastrointestinal and cardiovascular harm shows that while complicated gastrointestinal events occur more frequently with NSAIDs than coxibs , serious cardiovascular events occur at approximately equal rates . For each coxib , the reduction in complicated upper gastrointestinal events was numerically greater than any increase in APTC events Abstract A previously established relationship for deriving dichotomous from continuous information in r and omised controlled trials ( RCTs ) of analgesics has been tested using an independent data set . Individual patient information from 18 RCTs of parallel‐group design in acute postoperative pain ( after abdominal , gynaecological and oral surgery ) was used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) and the proportion of patients with > 50%maxTOTPAR for the different treatments . The relationship between the measures was investigated in 85 treatments with over 3400 patients . In 80 of 85 treatments ( 94 % ) agreement between calculated and actual number of patients with > 50%maxTOTPAR was within four patients per treatment and in 72 ( 85 % ) was within three ( average of 40 patients per treatment , range 21–58 patients ) . Summing the positive and negative differences between actual and calculated numbers of patients with > 50%maxTOTPAR gave an average difference of 0.30 patients per treatment arm . Reports of RCTs of analgesics frequently describe results of studies in the form of mean derived indices , rather than using discontinuous events , such as number or proportion of patients with 50 % pain relief . Because mean data inadequately describe information with a non‐normal distribution , combining mean data in systematic review s may compromise the results . Showing that dichotomous data can reliably be derived from mean data in acute pain studies enables data published as means to be used for quantitative systematic review s which require data in dichotomous form & NA ; Reports of RCTs of analgesics frequently describe results of studies in the form of mean derived indices , rather than using discontinuous events — such as number or proportion of patients with 50 % pain relief . Because mean data inadequately describe information with a non‐normal distribution , combining mean data in systematic review s may compromise the results . Showing that dichotomous data can reliably be derived from mean data , at least in acute pain models , indicates that more meaningful overviews or meta‐ analysis may be possible . This study investigated the relationship between continuous and dichotomous analgesic measures in a set of individual patient data , and then used that relationship to derive dichotomous from continuous information in r and omised controlled trials ( RCTs ) of analgesics . Individual patient information from 13 RCTs of parallel‐group and crossover design in acute postoperative pain was used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) and the proportion of patients with greater than 50 % pain relief ( > 50%maxTOTPAR ) for the different treatments . The relationship between the measures was investigated in 45 actual treatments and 10 000 treatments simulated using the underlying actual distribution ; 1283 patients had 45 separate treatments . Mean % maxTOTPAR correlated with the proportion of patients with > 50%maxTOTPAR ( r2 = 0.90 ) . The relationship calculated from all the 45 treatments predicted to within three patients the number of patients with more than 50 % pain relief in 42 of 45 treatments , and 98.8 % of 10 000 simulated treatments . For seven effective treatments , actual numbers‐needed‐to‐treat ( NNT ) to achieve > 50%maxTOTPAR compared with placebo were very similar to those derived from calculated data In a double-blind clinical trial a new , non-steroidal anti-inflammatory agent with analgesic properties , Fenbufen , was compared to acetylsalicylic acid ( ASA ) and placebo . Six hundred ( 600 ) out- patients , following surgical removal of an impacted lower wisdom tooth , were divided into three groups and r and omly given either Fenbufen ( 500 mg capsules ) , ASA ( 750 mg capsules ) , or placebo . One capsule was taken immediately after the surgical procedure , followed by another capsule every 6 hours . The duration of treatment was 24 hours . Thus , a total of 4 capsules were taken . Self-evaluation forms were provided to the patients and were returned to the investigators the following day . The results were statistically analyzed . Both Fenbufen and ASA were statistically superior ( p ≤ 0.01 ) to placebo in relieving pain . A comparison of the Fenbufen and ASA groups demonstrated a statistically significant ( p ≤ 0.05 ) superiority for Fenbufen in relieving pain . Also sleep was less disturbed in the Fenbufen group . Side-effects reported were few , minor in character , and fewer in number in the Fenbufen group & NA ; A data base of r and omised clinical trials ( RCTs ) in pain research published from 1950 to 1990 was created following an extensive literature search . By applying a refined MEDLINE search strategy from 1966 to 1990 and by h and ‐ search ing more than 1 000 000 pages of a total of 40 biomedical journals published during the period 1950–1990 , more than 8000 RCTs were identified . The RCTs were published in more than 800 journals and over 85 % appeared between 1976 and 1990 . If the trend of the last 15 years persists , a total of more than 15 000 RCTs will be published in pain relief by the year 2000 . A detailed description of methods to ensure efficient use of re sources during the identification , retrieval and management of the information in pain relief and other fields is given . Emphasis is made on the importance of refining MEDLINE search strategies , on the use of volunteers to h and ‐ search journals and on careful monitoring of each of the steps of the process . The potential uses of the data base to guide clinical and research decisions are discussed Abstract One way to ensure adequate sensitivity for analgesic trials is to test the intervention on patients who have established pain of moderate to severe intensity . The usual criterion is at least moderate pain on a categorical pain intensity scale . When visual analogue scales ( VAS ) are the only pain measure in trials we need to know what point on a VAS represents moderate pain , so that these trials can be included in meta‐ analysis when baseline pain of at least moderate intensity is an inclusion criterion . To investigate this we used individual patient data from 1080 patients from r and omised controlled trials of various analgesics . Baseline pain was measured using a 4‐point categorical pain intensity scale and a pain intensity VAS under identical conditions . The distribution of the VAS scores was examined for 736 patients reporting moderate pain and for 344 reporting severe pain . The VAS scores corresponding to moderate or severe pain were also examined by gender . Baseline VAS scores recorded by patients reporting moderate pain were significantly different from those of patients reporting severe pain . Of the patients reporting moderate pain 85 % scored over 30 mm on the corresponding VAS , with a mean score of 49 mm . For those reporting severe pain 85 % scored over 54 mm with a mean score of 75 mm . There was no difference between the corresponding VAS scores of men and women . Our results indicate that if a patient records a baseline VAS score in excess of 30 mm they would probably have recorded at least moderate pain on a 4‐point categorical scale Output:	In the absence of evidence of efficacy for oral fenbufen in acute postoperative pain , its use in this indication is not justified at present .
MS21233	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: What are the origins of the efficient language learning abilities that allow humans to acquire their mother tongue in just a few years very early in life ? Although previous studies have identified different mechanisms underlying the acquisition of auditory and speech patterns in older infants and adults , the earliest sensitivities remain unexplored . To address this issue , we investigated the ability of newborns to learn simple repetition-based structures in two optical brain-imaging experiments . In the first experiment , 22 neonates listened to syllable sequences containing immediate repetitions ( ABB ; e.g. , “ mubaba , ” “ penana ” ) , intermixed with r and om control sequences ( ABC ; e.g. , “ mubage , ” “ penaku ” ) . We found increased responses to the repetition sequences in the temporal and left frontal areas , indicating that the newborn brain differentiated the two patterns . The repetition sequences evoked greater activation than the r and om sequences during the first few trials , suggesting the presence of an automatic perceptual mechanism to detect repetitions . In addition , over the subsequent trials , activation increased further in response to the repetition sequences but not in response to the r and om sequences , indicating that recognition of the ABB pattern was enhanced by repeated exposure . In the second experiment , in which nonadjacent repetitions ( ABA ; e.g. , “ bamuba , ” “ napena ” ) were contrasted with the same r and om controls , no discrimination was observed . These findings suggest that newborns are sensitive to certain input configurations in the auditory domain , a perceptual ability that might facilitate later language development In adults , specific neural systems with right-hemispheric weighting are necessary to process pitch , melody , and harmony as well as structure and meaning emerging from musical sequences . It is not known to what extent the specialization of these systems results from long-term exposure to music or from neurobiological constraints . One way to address this question is to examine how these systems function at birth , when auditory experience is minimal . We used functional MRI to measure brain activity in 1- to 3-day-old newborns while they heard excerpts of Western tonal music and altered versions of the same excerpts . Altered versions either included changes of the tonal key or were permanently dissonant . Music evoked predominantly right-hemispheric activations in primary and higher order auditory cortex . During presentation of the altered excerpts , hemodynamic responses were significantly reduced in the rig1ht auditory cortex , and activations emerged in the left inferior frontal cortex and limbic structures . These results demonstrate that the infant brain shows a hemispheric specialization in processing music as early as the first postnatal hours . Results also indicate that the neural architecture underlying music processing in newborns is sensitive to changes in tonal key as well as to differences in consonance and dissonance The hypothesis that the ability to coordinate information between tactual and visual modalities is present at birth and dependent on perceptual inherent structures was tested in human newborns . Using an intersensory paired-preference procedure , we showed that newborns can visually recognize the shape of an object that they have previously manipulated with their right h and , out of sight . This is an experimental evidence that newborns can extract shape information in a tactual format and transform it in a visual format before they have had the opportunity to learn from the pairings of visual and tactual experience . This is contrary to a host of theories and models of perceptual learning , both traditional ( empiricist philosophers ) and modern ( connectionist ) Output:	RESULTS Studies have demonstrated that the coordination is a visually guided goal -directed motor behavior with intension and emotion . Current cognitive research has proved that feeding requires a large-scale neural network extending over several cortices . The eye-h and -mouth coordination in the newborn can be regarded as a precursor of subsequent self-feeding , and the coordination is very likely mediated through the underdeveloped but essentially the same network interconnecting cortices as in the adult
MS21234	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Lymphovascular invasion ( LVI ) in colorectal cancer ( CRC ) is considered a strong stage-independent prognostic factor and influences decisions regarding adjuvant chemotherapy in patients with stage II tumors . However , the degree of interobserver agreement among pathologists for LVI in CRC is largely unknown . This study was undertaken to examine such interobserver variability , and we hypothesized that the use of immunohistochemical markers for vascular and lymphatic channels could improve interobserver agreement . Design Fifty cases of American Joint Committee on Cancer stage II moderately differentiated CRC from 1990 to 2005 from the pathology archives were selected ; mucinous , medullary , and other recognized special subtypes were excluded . Fifty hematoxylin and eosin ( H&E ) slides ( 1 from each case ) were circulated to 6 gastrointestinal pathologists , who independently assessed small and large vessel invasion . No diagnostic guidelines were given to the participating pathologists ; each was instructed to apply the criteria for LVI that he or she used in daily practice . Immunohistochemistry ( IHC ) for D2 - 40 and CD31 was performed on corresponding paraffin blocks . The IHC slides were r and omized , recirculated , and rescored for LVI . Results were analyzed by kappa ( κ ) statistics , which correct for agreement by chance , and for percentage agreement . Results The average κ values were determined for the H&E slides ( large and small vessel ) , CD31 ( small vessel ) , and D2 - 40 ( small vessel ) ( Fig. 1 ) . Agreement was fair for H&E small vessel invasion [ κ=0.28 ; 95 % confidence interval ( CI ) : 0.22 - 0.34 ] . The least agreement was seen in interpretation of H&E large vessel invasion ( κ=0.18 ; 95%CI : 0.11 - 0.26 ) . Agreement was not improved by use of immunohistochemical stains : CD31 ( large vessel , κ=0.42 , 95%CI : 0.20 - 0.63 , small vessel , κ=0.26 , 95%CI : 0.10 - 0.42 ) and D2 - 40 ( κ=0.32 , 95%CI : 0.21 - 0.42 ) . Conclusions Interobserver variability in diagnosis of LVI was substantial on H&E slides and did not improve upon use of IHC . Agreement in evaluation of large vessel invasion was only slightly higher than would be seen by chance alone . This study highlights the need for criteria in evaluation of LVI , as this assessment may impact patient prognosis and thus change the course of clinical treatment Background Lymph node status is the most important prognostic factor for colorectal cancer . The number of lymph nodes that should be histologically examined has been controversial . The aims of this study were to assess the impact of the number of lymph nodes examined on survival of patients with stage II colorectal cancer and to determine the optimal number of lymph nodes that should be examined . Methods The study included 664 patients who underwent resection for stage II colorectal cancer . The clinical and histopathologic data of the patients were prospect ively collected and analyzed . Results The median number of lymph nodes examined was 12 ( range : 1 to 58 ) . The 5-year disease free survival rate was significantly higher for patients with 12 or more lymph nodes examined compared to those with less than 12 lymph nodes examined . The significant difference in 5-year disease free survival persisted if the dividing number increased progressively from 12 to 23 . However , the difference in survival was most significant ( lowest p value and highest hazard ratio ) for the number 21 . The 5-year disease free survival of patients with 21 or more lymph nodes examined was 80 % whereas that of patients with less than 21 lymph nodes examined was 60 % ( p = 0.001 , hazard ratio 2.08 ) . Multivariate analysis showed that 21 or more lymph nodes examined was a factor that independently influenced survival . The 5-year disease free survival also increased progressively with the number of lymph node examined up to the number 21 . After the number 21 , the survival rate did not increase further . It was likely that 21 was the optimal number , at and above which the chance of lymph node metastasis was minimal . Conclusions The number of lymph nodes examined in colorectal cancer specimen significantly influences survival . It is recommended that at least 21 lymph nodes should be examined for accurate diagnosis of stage II colorectal cancer BACKGROUND The aim of the QUASAR trial was to determine the size and duration of any survival benefit from adjuvant chemotherapy for patients with colorectal cancer at low risk of recurrence , for whom the indication for such treatment is unclear . METHODS After apparently curative resections of colon or rectal cancer , 3239 patients ( 2963 [ 91 % ] with stage II [ node negative ] disease , 2291 [ 71 % ] with colon cancer , median age 63 [ IQR 56 - 68 ] years ) enrolled between May , 1994 , and December , 2003 , from 150 centres in 19 countries were r and omly assigned to receive chemotherapy with fluorouracil and folinic acid ( n=1622 ) or to observation ( with chemotherapy considered on recurrence ; n=1617 ) . Chemotherapy was delivered as six 5-day courses every 4 weeks or as 30 once-weekly courses of intravenous fluorouracil ( 370 mg/m2 ) with high-dose ( 175 mg ) L-folinic acid or low-dose ( 25 mg ) L-folinic acid . Until 1997 , levamisole ( 12 courses of 450 mg over 3 days repeated every 2 weeks ) or placebo was added . After 1997 , patients who were assigned to receive chemotherapy were given fluorouracil and low-dose folinic acid only . The primary outcome was all-cause mortality . Analyses were done by intention to treat . This trial is registered with the International Clinical Trial Registry , number IS RCT N82375386 . FINDINGS At the time of analysis , 61 ( 3.8 % ) patients in the chemotherapy group and 50 ( 3.1 % ) in the observation group had missing follow-up . After a median follow-up of 5.5 ( range 0 - 10.6 ) years , there were 311 deaths in the chemotherapy group and 370 in the observation group ; the relative risk of death from any cause with chemotherapy versus observation alone was 0.82 ( 95 % CI 0.70 - 0.95 ; p=0.008 ) . There were 293 recurrences in the chemotherapy group and 359 in the observation group ; the relative risk of recurrence with chemotherapy versus observation alone was 0.78 ( 0.67 - 0.91 ; p=0.001 ) . Treatment efficacy did not differ significantly by tumour site , stage , sex , age , or chemotherapy schedule . Eight ( 0.5 % ) patients in the chemotherapy group and four ( 0.25 % ) in the observation group died from non-colorectal cancer causes within 30 weeks of r and omisation ; only one of these deaths was deemed to be possibly chemotherapy related . INTERPRETATION Chemotherapy with fluorouracil and folinic acid could improve survival of patients with stage II colorectal cancer , although the absolute improvements are small : assuming 5-year mortality without chemotherapy is 20 % , the relative risk of death seen here translates into an absolute improvement in survival of 3.6 % ( 95 % CI 1.0 - 6.0 ) Background Colorectal carcinoma is the most common malignancy of the gastrointestinal tract . It remains controversial for adjuvant chemotherapy in patients with stage II colon cancer . This study was design ed to identify the risk factors of tumor recurrence in stage II colon cancer . Furthermore , the benefit of adjuvant chemotherapy for high-risk stage II colorectal cancer will be investigated . Material s and methods From May 1998 until August 2004 , 375 patients with stage II ( T3N0M0 , T4N0M0 ) colon cancer received curative operation in a single hospital . The clinical data were extracted from the prospect ively collected colorectal cancer data base . The disease-free survival curves were calculated with Kaplan – Meier ’s analysis , and the survival difference was determined by log-rank test . The p value less than 0.05 was considered to be significant . Results Of 375 stage II colon cancer , 66 patients received 5-FU-based adjuvant chemotherapy , either oral or intravenous ( IV ) form . Within the median of 48.5 months of follow-up , recurrence developed in 35 patients ( 9.3 % ) . T4 lesion ( p=0.024 ) , lymphovascular invasion ( p=0.022 ) , obstruction at presentation ( p=0.008 ) , and mucinous component more than 50 % ( p=0.032 ) were associated with significantly decreased disease-free survival . High-risk patients ( n=102 ) , but not other patients with stage II colon cancer , benefited from adjuvant therapy ( 3-year disease-free survival : 96.4 % vs. 84.7 % , p=0.045 ; 5-year overall survival : 100 % vs. 86.4 % , p=0.015 ) . Conclusion Adjuvant therapy for high-risk stage II colon cancer may be beneficial , and we suggest adjuvant therapy should be considered in high-risk stage II colon cancer patients PURPOSE A greater underst and ing of the biology of tumor recurrence should improve adjuvant treatment decision making . We conducted a validation study of the 12-gene recurrence score ( RS ) , a quantitative assay integrating stromal response and cell cycle gene expression , in tumor specimens from patients enrolled onto Cancer and Leukemia Group B ( CALGB ) 9581 . PATIENTS AND METHODS CALGB 9581 r and omly assigned 1,713 patients with stage II colon cancer to treatment with edrecolomab or observation and found no survival difference . The analysis reported here included all patients with available tissue and recurrence ( n = 162 ) and a r and om ( approximately 1:3 ) selection of nonrecurring patients . RS was assessed in 690 formalin-fixed paraffin-embedded tumor sample s with quantitative reverse transcriptase polymerase chain reaction by using prespecified genes and a previously vali date d algorithm . Association of RS and recurrence was analyzed by weighted Cox proportional hazards regression . RESULTS Continuous RS was significantly associated with risk of recurrence ( P = .013 ) as was mismatch repair ( MMR ) gene deficiency ( P = .044 ) . In multivariate analyses , RS was the strongest predictor of recurrence ( P = .004 ) , independent of T stage , MMR , number of nodes examined , grade , and lymphovascular invasion . In T3 MMR-intact ( MMR-I ) patients , prespecified low and high RS groups had average 5-year recurrence risks of 13 % ( 95 % CI , 10 % to 16 % ) and 21 % ( 95 % CI , 16 % to 26 % ) , respectively . CONCLUSION The 12-gene RS predicts recurrence in stage II colon cancer in CALGB 9581 . This is consistent with the importance of stromal response and cell cycle gene expression in colon tumor recurrence . RS appears to be most discerning for patients with T3 MMR-I tumors , although markers such as grade and lymphovascular invasion did not add value in this subset of patients BACKGROUND A high-risk group of patients with stage II colon cancer has been identified by the results of studies in Western population s. The aim of this study was to investigate the prognostic factors of adjuvant chemotherapy in Turkish patients with stage II colon cancer . METHODS A total of 554 stage II colon cancer patients were retrospectively enrolled in the study . Three hundred fifty-three patients had received adjuvant chemotherapy ( 5-FU-LV , FOLFOX or FLOX ) and 201 had received no adjuvant chemotherapy . T4 tumor stage , lymphovascular invasion , perineural invasion , bowel obstruction and /or perforation , < 12 harvested lymph nodes , and poor differentiation were defined as high-risk factors . RESULTS The median age of the patients was 62 years ( range 26 - 88 ) . The median disease-free survival ( DFS ) was 58.1 months ( 95 % CI , 47.6 months to 68.5 months ) in the non-treatment group and has not been reached in the treatment group ( P < 0.01 ) . In univariate analysis , patient age > 60 years and T4 tumor stage were statistically significant factors that affected DFS as poor prognostic factors . Adjuvant chemotherapy reduced the risk of recurrence with statistical significance ( P < 0.01 ) . In multivariate analysis , patient age > 60 years and T4 tumor stage were independent risk factors affecting DFS . In addition , adjuvant chemotherapy was an independent favorable prognostic factor for DFS ( P < 0.01 ) . CONCLUSIONS Clinical and pathological risk factors in patients with stage II colon cancer may be different in the Turkish population compared to other population s. Further prospect Output:	Further subgroup analysis revealed that the significance of the association between LVI and worse prognosis in CRC patients is not affected by below factors , including geographic setting , LVI positive rate , treatment , tumor site , and quality of the study . The current meta- analysis suggests that LVI may be a poor prognostic factor for stage I/II CRC patients
MS21235	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Purpose : To examine the performance of an instrument to assess adherence based on a visual analogue scale , compared to an instrument based on 3-day recall , using unannounced pill counts in the place of residence as the gold st and ard . Method : We prospect ively assessed adherence to antiretroviral therapy in 84 marginally housed indigent HIV-infected patients who were receiving stable antiretroviral therapy in San Francisco , California , with three adherence assessment s over no more than 4 months . Results : Mean adherence using the visual analogue scale , 3-day recall , and unannounced pill count methods were 82.5 % , 84.2 % , and 75.9 % , respectively . The correlation between visual analogue scale and unannounced pill count was high ( r = 0.76 ) and was not statistically different from that between 3-day recall and unannounced pill count ( r = 0.71 ; p = .52 ) . Both methods were also similarly inversely correlated with HIV viral load ( r = -0.49 and -0.34 , respectively ; p = .22 for the difference in the correlations ) . The visual analogue scale correlation with unannounced pill count was stable over time and remained high in all sub population s examined . Conclusion : A visual analogue scale to assess adherence was performed as well as a more complicated 3-day recall instrument in this diverse population . Given its simplicity , the visual analogue scale adherence instrument will be useful in research and may be useful in routine patient care High blood pressure ( HBP ) is one of the most important risk factors for morbidity and mortality in the world . Non-adherence to medication is associated with the lack of control of HBP . The objective of this study was to assess the validity of four indirect methods for measuring adherence to medication to control HBP in primary health care . A r and om sample of 120 hypertensive patients who were undergoing treatment for at least 2 months in a primary care unit in Florianópolis ( Brazil ) were included in the study . The independent variables were four indirect methods to measure adherence to medication : knowledge regarding the HBP medication , the blood pressure level , attitude regarding the medication intake ( Morisky – Green test ) and self-reported adherence . The classification of HBP was based on criteria established by the Brazilian Ministry of Health . The gold st and ard used for measuring adherence was the pill count . Logistic regression was used to estimate sensitivity ( highest value of 88.2 % for self-report ) , specificity ( highest value of 70.7 % for HBP control ) , positive predictive value ( highest value of 46.4 % for HBP control ) and negative predictive value ( highest value of 79.1 % for Morisky – Green test ) for each of the indirect methods . No indirect method of measuring adherence had a good positive predictive value for adherence , which was best predicted by patients ' age and whether they managed to control HBP . The results also revealed low treatment adherence ( 31.2 % ) and low control of HBP ( 37.6 % ) . Non-adherence was mainly associated with side effects of the treatment AIDS Clinical Trials Group ( ACTG ) 359 was a r and omized , partially double-blinded factorial study of 6 antiretroviral regimens , all including saquinavir , among HIV-infected persons in whom prior therapy had failed ( n = 258 ) . Counts of remaining saquinavir capsules were determined between weeks 0 and 4 ; at weeks 4 , 8 , and 16 , self-reported adherence was estimated from 2-day report of doses skipped , therapeutic coverage , and percent of doses taken were determined by electronic monitoring devices applied to saquinavir bottles , and the saquinavir 24-hour area under the curve ( AUC ) was estimated . Relationships were evaluated among these 4 adherence measures and the primary endpoint of week 16 HIV RNA change . Thirty percent of 254 subjects had HIV RNA ≤500 copies/mL at week 16 . Only self-reported adherence and saquinavir AUC were significantly associated with week 16 HIV RNA change ( P = 0.019 and 0.023 , respectively ) , and these measures were higher in subjects with week 16 HIV RNA ≤500 copies/mL ( P = 0.03 and 0.008 , respectively ) . The ability to detect a correlation between electronically monitored adherence and virologic response was limited by the small sample size . Self-reported adherence and saquinavir AUC were significant predictors of virologic response , in this evaluation . These findings provide insight into methods of assessing and improving adherence to antiretroviral regimens BACKGROUND Nonadherence to physician treatment recommendations is an increasingly recognized cause of adverse outcomes and increased health care costs , particularly among patients with cardiovascular disease . Whether patient self-report can provide an accurate assessment of medication adherence in out patients with stable coronary heart disease is unknown . METHODS We prospect ively evaluated the risk of cardiovascular events associated with self-reported medication nonadherence in 1015 out patients with established coronary heart disease from the Heart and Soul Study . We asked participants a single question : " In the past month , how often did you take your medications as the doctor prescribed ? " Nonadherence was defined as taking medications as prescribed 75 % of the time or less . Cardiovascular events ( coronary heart disease death , myocardial infa rct ion , or stroke ) were identified by review of medical records during 3.9 years of follow-up . We used Cox proportional hazards analysis to determine the risk of adverse cardiovascular events associated with self-reported medication nonadherence . RESULTS Of the 1015 participants , 83 ( 8.2 % ) reported nonadherence to their medications , and 146 ( 14.4 % ) developed cardiovascular events . Nonadherent participants were more likely than adherent participants to develop cardiovascular events during 3.9 years of follow-up ( 22.9 % vs 13.8 % , P = .03 ) . Self-reported nonadherence remained independently predictive of adverse cardiovascular events after adjusting for baseline cardiac disease severity , traditional risk factors , and depressive symptoms ( hazards ratio , 2.3 ; 95 % confidence interval , 1.3 - 4.3 ; P = .006 ) . CONCLUSIONS In out patients with stable coronary heart disease , self-reported medication nonadherence is associated with a greater than 2-fold increased rate of subsequent cardiovascular events . A single question about medication adherence may be a simple and effective method to identify patients at higher risk for adverse cardiovascular events The relationship between adherence to highly active antiretroviral therapy ( HAART ) and RNA-HIV viral load outcomes has been extensively shown . Although there are different procedures for assessing treatment adherence , there is no ideal method . We present the SERAD ( Self-Reported Adherence ) question naire , a qualitative and quantitative self-reported instrument design ed to provide an easier adherence measurement . We also compared the question naire to three other methods to evaluate adherence to HAART regimens in HIV-infected patients . Two prospect i ve , observational , longitudinal studies were developed : a single-center pilot study followed by a multicenter study . A total of 530 HIV-infected out patients was prospect ively included , 66 in the pilot study and 464 in the multicenter study . Four methods were used to study adherence to HAART regimens : the SERAD question naire , pill count , electronic monitoring , and plasma drug monitoring . Pearson 's correlations and Bl and and Altman 's method were developed . The SERAD question naire showed good feasibility and significant validity . Adequate levels of agreement between methods were observed , particularly when adherence was high . Differences increased as adherence fell . Moreover , the question naire was completed correctly , the interviewers did not report uncovered aspects , and the information was collected easily . Our results suggest that the SERAD question naire is a feasible and useful instrument for assessing adherence to HAART regimens in HIV-infected patients , and makes it possible to obtain reliable qualitative and quantitative information related to treatment adherence A step-wise approach to identify valid and feasible methods to detect non-adherence to tuberculosis drugs was evaluated in a prospect i ve study among pulmonary tuberculosis patients in an outpatient clinic in Indonesia . First , adherence was measured by self-reporting with the st and ardized Morisky question naire , physician assessment , pill-count , visit attendance , diary and an electronic medication event monitoring system ( MEMS ) . Next , validity of single methods was assessed against MEMS as gold st and ard . Feasibility of methods was then judged by physicians in the field . Finally , when valid and feasible methods were combined , it appeared that self-reporting by a question naire plus physician assessment could identify all non-adherent patients . It is recommended to use a systematic approach to develop a valid and locally feasible combination of methods to detect non-adherence to TB drugs Nonadherence to immunosuppressants in renal transplant recipients is a major factor affecting graft survival , but it is difficult to detect accurately in clinical practice . Adherence was measured in 153 adult renal transplant recipients using self-report question naires and interview , clinician rating , and cyclosporine levels . The sensitivity and specificity of these measures were determined by comparison with electronic monitoring in a r and omly selected sub sample of 58 subjects . Measures of adherence in current clinical use do not perform well when tested against electronic monitoring . Self-report at a confidential interview was the best measure of adherence for the detection of both missed doses and erratic timing of medication . However , the use of a confidential interview is not directly applicable to a clinical setting . Further research on how best to facilitate disclosure in clinical setting s may be the best way to develop adherence measures for use in routine practice A two-group r and omized experimental design was employed to assess the effects of monitoring and feedback on the compliance of 93 psychiatric out patients treated with lithium . Compliance in both groups was measured using self-report , lithium level , appointment-keeping , and medication refill frequency . The experimental group was also monitored using a unique electronic device that records the time and day pills are removed . At the midpoint of the study , the experimental group received feedback about serum lithium levels and patterns of removing medications from the monitoring device while the control group received feedback about serum lithium levels only . The study demonstrated no sustained effect of the monitoring and feedback interventions on compliance Improved therapeutic strategies , including the introduction of protease inhibitors , have led to a striking decrease in HIV-related morbidity and mortality ( 1 , 2 ) . It is widely believed that adherence to an antiretroviral regimen is central to the likelihood that a patient will derive sustained benefit from therapy ( 3 , 4 ) . Conventional wisdom holds that two groups of patients are currently experiencing clinical and virologic failure . The first group consists of patients who have received multiple different antiretroviral drugs over a prolonged period of time and who may be infected predominantly with HIV strains that are resistant to multiple drugs . The second group comprises patients who adhere poorly to their antiretroviral regimen . The two groups are not mutually exclusive : Patients with suboptimal adherence may be more likely to have antiretroviral drugresistant HIV infection . The potential public health importance of adherence to therapy in prevention of transmission of drug-resistant virus has also been emphasized ( 5 ) . Patients with suboptimal adherence to antiretroviral therapy and poor adherence to use of safer-sex practice s , such as use of condoms , may infect others with their own antiretroviral drugresistant virus . Anecdotal experience suggests that physicians may be unwilling to prescribe combination antiretroviral therapy to patients whom they perceive to be at high risk for poor adherence ( 6 ) . Given the critical importance of adherence to therapy to patient outcome , secondary prevention of HIV infection , and willingness of providers to prescribe therapy , we prospect ively investigated the association between protease inhibitor adherence and patient outcome , factors related to adherence , and the accuracy of physicians ' prediction of patient adherence . We used a microelectronic monitoring system to assess adherence to antiretroviral therapy . Methods Study Sample The study was conducted at the HIV clinics of the Veterans Affairs Medical Center , Pittsburgh , Pennsylvania , and University of Nebraska Medical Center , Omaha , Nebraska . The HIV physicians at these clinics were primary care providers for the study patients . Each site also had a dedicated HIV nurse coordinator . From August 1997 to March 1999 , we enrolled consecutive patients with HIV infection who were already receiving a protease inhibitor ( experienced patients ) or who were to begin taking a protease inhibitor ( naive patients ) . Exclusion criteria were inability to give informed written consent ; expectation of continued use of a medication organizer to include protease inhibitors ; and residence in a nursing home , jail , or hospice , where medications were dispensed at least daily . Collection of Baseline Data At baseline , a study investigator used medical chart review to complete a 52-item question naire for each patient . The question naire covered demographic information ( age , sex , ethnicity , risk factors for HIV infection , educational and employment status , income ) , medical history ( years known to be HIV infected ; opportunistic infections ; history of schizophrenia , depression , or bipolar affective disorder ) , and medication use ( name , dose , and frequency of all antiretroviral agents , other antimicrobials , and other prescription therapies ) . The enrolling physician assessed use of illegal drugs and nonprescription therapies ( including herbal or alternative therapies ) by interview . Alcohol abuse was assessed by using Output:	Few were design ed to have the ability to be completed by or in conjunction with carers and few were able to distinguish between different types of non-adherence , which limited their ability be used effectively in the continuous improvement of targeted adherence enhancing interventions . The data available suggested that patients find it easier to estimate general adherence than to report a specific number of doses missed . Visual analogue scales can be easier for patients than other types of scale but are not suitable for telephone administration .
MS21236	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: It is thought that antenatal pelvic floor muscle training ( PFMT ) might produce a strong pelvic floor result ing in prolonged labour , whilst some believe it produces well-controlled muscles that facilitate rotation of the foetal head and shortens the duration of labour . This secondary analysis ( of a previously published r and omised controlled trial ) assesses the labour and delivery details of 268 primigravidae who were originally r and omised at approximately 20 weeks gestation to supervised PFMT or a control group . Between the two groups , there was no difference in the duration of the second stage of labour or in the need for instrumental delivery . PFMT does not appear to facilitate or obstruct labour Epidemiological studies have postulated racial differences in the incidence and prevalence of pelvic floor disorders . There are anecdotal data from cadaver dissections suggesting that Asian women benefit from stronger pelvic support structures . A prospect i ve observational clinical study was conducted in order to test for differences in pelvic organ support in 200 nulliparous pregnant women . Assessment included translabial ultrasound , documenting the position of the pelvic organs and mobility on Valsalva relative to the inferoposterior symphyseal margin . The largest ethnic groups were Asian ( n=16 ) and Caucasian women ( n=161 ) . On comparing the groups , both antepartum and postpartum analyses showed significantly less pelvic organ mobility in Asians . This was true for virtually all parameters of organ mobility and both anterior ( P=0.002 antepartum , P=0.009 postpartum ) and posterior compartments ( P=0.04 antepartum , P=0.02 postpartum ) . No significant differences were detected for cervical mobility . It was concluded that Asian women seem to show less mobility of the anterior and posterior vaginal compartments than Caucasians OBJECTIVE : This study aim ed to compare the pelvic floor muscle strength of nulliparous and primiparous women . METHODS : A total of 100 women were prospect ively distributed into two groups : Group 1 ( G1 ) ( n = 50 ) included healthy nulliparous women , and Group 2 ( G2 ) ( n = 50 ) included healthy primiparous women . Pelvic floor muscle strength was subjectively evaluated using transvaginal digital palpation . Pelvic floor muscle strength was objective ly assessed using a portable perineometer . All of the parameters were evaluated simultaneously in G1 and were evaluated in G2 during the 20th and 36th weeks of pregnancy and 45 days after delivery . RESULTS : In G2 , 14 women were excluded because they left the study before the follow-up evaluation . The median age was 23 years in G1 and 22 years in G2 ; there was no significant difference between the groups . The average body mass index was 21.7 kg/m2 in G1 and 25.0 kg/m2 in G2 ; there was a significant difference between the groups ( p = 0.0004 ) . In G2 , transvaginal digital palpation evaluation showed significant impairments of pelvic floor muscle strength at the 36th week of pregnancy ( p = 0.0006 ) and 45 days after vaginal delivery ( p = 0.0001 ) compared to G1 . Objective evaluations of pelvic floor muscle strength in G2 revealed a significant decrease 45 days after vaginal delivery compared to nulliparous patients . CONCLUSION : Pregnancy and vaginal delivery may cause weakness of the pelvic floor muscles OBJECTIVE Urinary incontinence is a chronic health complaint that severely reduces quality of life . Pregnancy and vaginal delivery are main risk factors in the development of urinary incontinence . The aim of this study was to assess whether intensive pelvic floor muscle training during pregnancy could prevent urinary incontinence . METHODS We conducted a single-blind r and omized controlled trial at Trondheim University Hospital and three outpatient physiotherapy clinics in a primary care setting . Three hundred one healthy nulliparous women were r and omly allocated to a training ( n = 148 ) or a control group ( n = 153 ) . The training group attended a 12-week intensive pelvic floor muscle training program during pregnancy , supervised by physiotherapists . The control group received the customary information . The primary outcome measure was self-reported symptoms of urinary incontinence . The secondary outcome measure was pelvic floor muscle strength . RESULTS At follow-up , significantly fewer women in the training group reported urinary incontinence : 48 of 148 ( 32 % ) versus 74 of 153 ( 48 % ) at 36 weeks ' pregnancy ( P = .007 ) and 29 of 148 ( 20 % ) versus 49 of 153 ( 32 % ) 3 months after delivery ( P = .018 ) . According to numbers needed to treat , intensive pelvic floor muscle training during pregnancy prevented urinary incontinence in about one in six women during pregnancy and one in eight women after delivery . Pelvic floor muscle strength was significantly higher in the training group at 36 weeks ' pregnancy ( P = .008 ) and 3 months after delivery ( P = .048 ) . CONCLUSION Intensive pelvic floor muscle training during pregnancy prevents urinary incontinence during pregnancy and after delivery . Pelvic floor muscle strength improved significantly after intensive pelvic floor muscle training Abstract Objective : To compare the effect of pelvic floor exercises , electrical stimulation , vaginal cones , and no treatment for genuine stress incontinence . Design : Stratified , single blind , r and omised controlled trial . Setting : Multicentre . Participants : 107 women with clinical ly and urodynamically proved genuine stress incontinence . Mean ( range ) age was 49.5 ( 24 - 70 ) years , and mean ( range ) duration of symptoms 10.8 ( 1 - 45 ) years . Interventions : Pelvic floor exercise ( n=25 ) comprised 8 - 12 contractions 3 times a day and exercise in groups with skilled physical therapists once a week . The electrical stimulation group ( n=25 ) used vaginal intermittent stimulation with the MS 106 Twin at 50 Hz 30 minutes a day . The vaginal cones group ( n=27 ) used cones for 20 minutes a day . The untreated control group ( n=30 ) was offered the use of a continence guard . Muscle strength was measured by vaginal squeeze pressure once a month . Main outcome measures : Pad test with st and ardised bladder volume , and self report of severity . Results : Improvement in muscle strength was significantly greater ( P=0.03 ) after pelvic floor exercises ( 11.0 cm H2O ( 95 % confidence interval 7.7 to 14.3 ) before v 19.2 cm H2O ( 15.3 to 23.1 ) after ) than either electrical stimulation ( 14.8 cm H2O ( 10.9 to 18.7 ) v 18.6 cm H2O ( 13.3 to 23.9 ) ) or vaginal cones ( 11.8 cm H2O ( 8.5 to 15.1 ) v 15.4 cm H2O ( 11.1 to 19.7 ) ) . Reduction in leakage on pad test was greater in the exercise group ( −30.2 g ; −43.3 to 16.9 ) than in the electrical stimulation group ( −7.4 g ; −20.9 to 6.1 ) and the vaginal cones group ( −14.7 g ; −27.6 to −1.8 ) . On completion of the trial one participant in the control group , 14 in the pelvic floor exercise group , three in the electrical stimulation group , and two in the vaginal cones group no longer considered themselves as having a problem . Conclusion : Training of the pelvic floor muscles is superior to electrical stimulation and vaginal cones in the treatment of genuine stress incontinence OBJECTIVE Prospect i ve study to objective ly evaluate the benefits of pelvic floor strengthening exercises associated to biofeedback for the treatment of stress urinary incontinence . MATERIAL S AND METHODS Fourteen patients diagnosed with stress urinary incontinence ( SUI ) were selected for this study . All patients underwent a pelvic floor training associated to biofeedback for 12 consecutive weeks . Urodynamic tests , pad test and bladder diary were analyzed at the beginning of the study , at the end and after 3 months . The King 's Health Question naire ( KHQ ) was applied before and after treatment to assess the impact in the quality of life . RESULTS There was a significant reduction in the pad weight ( from 14.21 g to 1 g ) , number of urinary leakage episodes ( from 8.14 per day to 2.57 per day ) and daytime frequency ( from 7.93 per day to 5.85 per day ) . At urodynamics the authors observed a significant increase in Valsalva leak-point pressure ( from 103.93 cm H2O to 139.14 cm H2O ) , cistometric capacity ( from 249.29 mL to 336.43 mL , p = 0.0015 ) and bladder volume at first desire to void ( from 145 mL to 215.71 mL ) . Those differences were kept during the first 3 months of follow up . The KHQ revealed significant differences except in the case of ' ' general health perception ' ' , which covers health in general and not exclusively urinary incontinence . CONCLUSION Treatment of SUI with pelvic floor exercises associated to biofeedback caused significant changes in the parameters analyzed , with maintenance of good results 3 months after treatment AIM This article is a report of a study of the effects of a pelvic floor muscle exercise programme on the severity of stress urinary incontinence in pregnant women . BACKGROUND Pregnancy is main risk factor for the development of stress urinary incontinence . Stress urinary incontinence can be cured by pelvic floor muscle exercise which is a safe inexpensive treatment with no complications and does not require the use of instruments . METHODOLOGY A quasi-experimental study , pre-post test with control group design was used at the antenatal care unit in a tertiary care hospital between June and October of 2006 . The participants were 66 pregnant women who had stress urinary incontinence with gestational ages of 20 - 30 weeks . The main outcome measure was severity of stress urinary incontinence which comprised frequency and amount of urine leakage and perceived severity of stress urinary incontinence . RESULTS After the experimental group 's participation in the pelvic floor muscle exercise programme , the frequency and amount of urine leakage and the score of perceived stress urinary incontinence severity were significantly lower than the same scores before participation in the programme . In addition , women in the experimental group had frequency and volume of urine leakage , and score of perceived stress urinary incontinence severity after participation significantly lower than those in the control group . CONCLUSION The 6-week pelvic floor muscle exercise programme was able to decrease the severity of symptoms in pregnant women with stress urinary incontinence Introduction and hypothesisThe aim of the study was to evaluate the effect of antenatal pelvic floor muscle exercise ( PFME ) in the prevention and treatment of urinary incontinence during pregnancy and postpartum period . Methods Three hundred women were r and omly assigned to the PFME group and control group . Urinary symptoms were measured by Urogenital Distress Inventory-6 ( UDI-6 ) , Incontinence Impact Question naire-7 ( IIQ-7 ) , and question of self-reported urinary incontinence . Question naire scores of the PFME and the control groups were compared and analyzed . Results During late pregnancy and the postpartum period , the PFME group had significantly lower total UDI-6 and IIQ-7 scores ; their self-report rate of urinary incontinence was also less than the control group . Additionally , we found whether in PFME or control , women who delivered vaginally were more likely to develop postpartum urinary leakage than women who delivered by cesarean section . Conclusions PFME applied in pregnancy is effective in the treatment and prevention of urinary incontinence during pregnancy , and this effect may persist to postpartum period Please cite this paper as : Stafne S , Salvesen K , Romundstad P , Torjusen I , Mørkved S. Does regular exercise including pelvic floor muscle training prevent urinary and anal incontinence during pregnancy ? A r and omised controlled trial . BJOG 2012;119:1270–1280 Introduction and hypothesisTheoretically , tight or strong pelvic floor muscles may impair the progress of labor and lead to instrumental deliveries . We aim ed to investigate whether vaginal resting pressure , pelvic floor muscle strength , or endurance at midpregnancy affect delivery outcome . Methods This was a prospect i ve cohort study of women giving birth at a university hospital . Vaginal resting pressure , pelvic floor muscle strength , and endurance in 300 nulliparous pregnant women were assessed at mean gestational week 20.8 ( ±1.4 ) using a high precision pressure transducer connected to a vaginal balloon . Delivery outcome measures [ acute cesarean section , prolonged second stage of labor ( > 2 h ) , instrumental vaginal delivery ( vacuum and forceps ) , episiotomy , and third- and fourth-degree perineal tear ) were retrieved from the hospital ’s electronic birth records . Results Twenty-three women were lost to follow-up , mostly because they gave birth at another hospital . Women with prolonged second stage had significantly higher resting pressure than women with second stage less than 2 h ; the mean difference was 4.4 cmH2O [ 95 % confidence interval ( CI ) 1.2–7 Output:	Conclusions Antenatal PFMT might be effective at shortening the first and second stage of labor in the primigravida . Antenatal PFMT may not increase the risk of episiotomy , instrumental delivery , and perineal laceration in the primigravida
MS21237	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Tai Chi , a moving meditation , is examined for its efficacy in post-stressor recovery . Forty-eight male and 48 female Tai Chi practitioners were r and omly assigned to four treatment groups : Tai Chi , brisk walking , mediation and neutral reading . Mental arithmetic and other difficult tests were chosen as mental challenges , and a stressful film was used to produce emotional disturbance . Tai Chi and the other treatments were applied after these stressors . After all treatments , the salivary cortisol level dropped significantly , and the mood states were also improved . In general the stress-reduction effect of Tai Chi characterized moderate physical exercise . Heart rate , blood pressure , and urinary catecholamine changes for Tai Chi were found to be similar to those for walking at a speed of 6 km/hr . Although Tai Chi appeared to be superior to neutral reading in the reduction of state anxiety and the enhancement of vigour , this effect could be partially accounted for by the subjects ' high expectations about gains from Tai Chi . Approaches controlling for expectancy level are recommended for further assessment Psychoneuroimmunology is a framework for mind-body practice and research that combines cutting-edge scientific exploration with holistic philosophy to appreciate and underst and stress responses . The rapidly growing research literature provides a foundation for building an integrative stress management model with the potential to positively influence the stress-disease relationship and , ultimately , health outcomes . This article introduces a novel tai chi intervention and provides quantitative and qualitative data from a r and omized clinical trial indicating its effects on psychosocial variables in individuals living with various stages of HIV disease BACKGROUND Stress can affect health . There is a growing need for the evaluation and application of professional stress management options , i.e , stress reduction . Mind/body medicine serves this goal , e.g , by integrating self-care techniques into medicine and health care . Tai Chi ( TC ) can be classified as such a mind/body technique , potentially reducing stress and affecting physical as well as mental health parameters , which , however , has to be examined further . MATERIAL / METHODS We conducted a prospect i ve , longitudinal pilot study over 18 weeks for the evaluation of subjective and objective clinical effects of a Yang style TC intervention in young adults ( beginners ) by measuring physiological ( blood pressure , heart rate , saliva cortisol ) and psychological ( SF-36 , perceived stress , significant events ) parameters , i.e , direct or indirect indicators of stress and stress reduction , in a non-r and omised/-controlled , yet non-selected cohort ( n=21 ) by pre-to-post comparison and in follow-up . SF-36 values were also compared with the age-adjusted norm population , serving as an external control . Additionally , we measured diurnal cortisol profiles in a cross-sectional sub- study ( n=2 + 2 , pre-to-post ) , providing an internal r and om control sub- sample . RESULTS Only nine participants completed all measurements . Even so , we found significant ( p<0.05 ) reductions of saliva cortisol ( post and follow-up ) , which seems to be an indicator of general stress reduction . A significant decrease in perceived mental stress ( post ) proved even highly significant ( p<0.01 ) in the follow-up , whereas physical stress perception declined to a much lesser degree . Significant improvements were also detected for the SF-36 dimensions general health perception , social functioning , vitality , and mental health/psychological well-being . Thus , the summarized mental health measures all clearly improved , pointing towards a predominantly psychological impact of TC . CONCLUSIONS Subjective health increased , stress decreased ( objective ly and subjectively ) during TC practice . Future studies should confirm this observation by rigorous methodology and by further combining physical and psychological measurements with basic research , thereby also gaining knowledge of autoregulation and molecular physiology that possibly underlies mind/body medicine Abstract Anxiety sensitivity , or the belief that anxiety-related sensations can have negative consequences , has been shown to play an important role in the etiology and maintenance of panic disorder and other anxiety-related pathology . Aerobic exercise involves exposure to physiological cues similar to those experienced during anxiety reactions . The present study sought to investigate the efficacy of a brief aerobic exercise intervention for high anxiety sensitivity . Accordingly , 24 participants with high anxiety sensitivity scores ( Anxiety Sensitivity Index-Revised scores > 28 ) were r and omly assigned to complete either six 20-minute sessions of aerobic exercise or a no-exercise control condition . The results indicated that individuals assigned to the aerobic exercise condition reported significantly less anxiety sensitivity subsequent to exercise , whereas anxiety sensitivity scores among non-exercisers did not significantly change . The clinical research and public health implication s of these findings are discussed , and several potential directions for additional research are recommended Objective : Alternative approaches to weight control and physical activity are increasingly needed . Numerous factors influence weight management , including the choice of physical exercise . No study has previously examined the therapeutic effect of a multidisciplinary weight management program incorporating Tai Chi ( TC ) exercises among sedentary obese women . Design : R and omized intervention trial with blinded medical provider . Setting : In day hospital consultations . Participants : Twenty-one obese women . Intervention : All subjects participated in a 10-week weight management program that was part of usual care and included a hypocaloric balanced diet , a weekly physician/psychologist/dietician group session , and an exercise program . For the exercise component , subjects were r and omized to either a 2-hour weekly session of TC or a conventional structured exercise program . Main Outcome Measures : Changes in weight , body composition , heart rate , blood pressure , mobility scores , mood , Three Factor Eating Question naire scores , and General Self-Efficacy . Results : The TC arm improved in resting systolic blood pressure , chair rise test , mood , and reduced percent of fat at week 10 and at 6 months follow-up . General self-efficacy was enhanced in both groups and maintained at 30 weeks . Conclusion : The observed benefits over a 30-week period of a multidisciplinary weight management program incorporating TC exercises on physical functioning mood and dietary restraint need further underst and ing of how sedentary obese women adhere to physical activity like TC or other alternative exercises Older persons who are willing to begin exercise programs are often not willing to continue them . At the Atlanta FICSIT ( Frailty and Injuries : Cooperative Studies of Intervention Techniques ) site , individuals aged 70 + were r and omized to Tai Chi ( TC ) , individualized balance training ( BT ) , and exercise control education ( ED ) groups for 15 weeks . In a follow-up assessment 4 months post-intervention , 130 subjects responded to exit interview questions asking about perceived benefits of participation . Both TC and BT subjects reported increased confidence in balance and movement , but only TC subjects reported that their daily activities and their overall life had been affected ; many of these subjects had changed their normal physical activity to incorporate ongoing TC practice . The data suggest that when mental as well as physical control is perceived to be enhanced , with a generalized sense of improvement in overall well-being , older persons ' motivation to continue exercising also increases Goals Health-related quality of life ( HRQL ) and self-esteem are often diminished among women diagnosed and treated for breast cancer . Tai Chi is a moderate form of exercise that may be an effective therapy for improving HRQL and self-esteem among these women . We sought to compare the efficacy of Tai Chi Chuan ( TCC ) and psychosocial support ( PST ) for improving HRQL and self-esteem among breast cancer survivors . Patients and methods A group of 21 women diagnosed with breast cancer , who had completed treatment within the last 30 months were r and omized to receive 12 weeks of TCC or PST . Participants in both groups met three times a week for 60 minutes . HRQL and self-esteem were assessed at baseline , 6 weeks , and 12 weeks . Results The TCC group demonstrated significant improvements in HRQL , while the PST group reported declines in HRQL , with the differences between the two groups approaching significance at week 12 . Additionally , the TCC group exhibited improvements in self-esteem , while the PST group reported declines in self-esteem , with the differences between groups reaching statistical significance at week 12 . These findings , coupled with a visual inspection of the raw change scores , support the plausibility of a dose-response relationship concerning Tai Chi . Conclusions In this pilot investigation , the TCC group exhibited improvements in HRQL and self-esteem from baseline to 6 and 12 weeks , while the support group exhibited declines . R and omized , controlled clinical trials with larger sample sizes are needed AIM This paper reports a study to examine change in psychosocial status following a 12-week Tai Chi exercise intervention among ethnic Chinese people with cardiovascular disease risk factors living in the United States of America . BACKGROUND Regular participation in physical activity is associated with protection against cardioavascular disease , and improvements in physical and psychological health . Increasing amounts of scientific evidence suggests that mind-body exercise , such as Tai Chi , are related to improvements in mental health , emotional well-being , and stress reduction . No prior study has examined the effect of a Tai Chi exercise intervention on psychosocial status among people with cardiovascular disease risk factors . METHODS This was a quasi-experimental study . Participants attended a 60-minute Tai Chi exercise class three times per week for 12 weeks . Data were collected at baseline , 6 and 12 weeks following the intervention . Psychosocial status was assessed using Chinese versions of Cohen 's Perceived Stress Scale , Profile of Mood States , Multidimensional Scale of Perceived Social Support , and Tai Chi exercise self-efficacy . RESULTS A total of 39 participants , on average 66-year-old ( + /-8.3 ) , married ( 85 % ) , Cantonese-speaking ( 97 % ) , immigrants participated . The majority were women ( 69 % ) , with < or = 12 years education ( 87 % ) . Statistically significant improvements in all measures of psychosocial status were found ( P < or = 0.05 ) following the intervention . Improvement in mood state ( eta2 = 0.12 ) , and reduction in perceived stress ( eta2 = 0.13 ) were found . In addition , Tai Chi exercise statistically significantly increased self-efficacy to overcome barriers to Tai Chi ( eta2 = 0.19 ) , confidence to perform Tai Chi ( eta2 = 0.27 ) , and perceived social support ( eta2 = 0.12 ) . CONCLUSIONS Tai Chi was a culturally appropriate mind-body exercise for these older adults , with statistically significant psychosocial benefits observed over 12-weeks . Further research examining Tai Chi exercise using a r and omized clinical trial design with an attention-control group may reduce potential confounding effects , while exploring potential mechanisms underlying the relaxation response associated with mind-body exercise . In addition , future studies with people with other chronic illnesses in all ethnic groups are recommended to determine if similar benefits can be achieved OBJECTIVES To determine whether an intense tai chi exercise program could reduce fear of falling better than a wellness education ( WE ) program in older adults who had fallen previously and meet criteria for transitioning to frailty . DESIGN Cluster-r and omized , controlled trial of 48 weeks ' duration . SETTING Ten matched pairs of congregate living facilities in the greater Atlanta area . PARTICIPANTS Sample of 291 women and 20 men , aged 70 to 97 . MEASUREMENTS Activity-related fear of falling using the Activities-Specific Balance Confidence Scale ( ABC ) and the Fall Efficacy Scale at baseline and every 4 months for 1 year . Demographics , time to first fall and all subsequent falls , functional measures , Centers for Epidemiologic Studies Depression Scale , medication use , level of physical activity , comorbidities , and adherence to interventions . RESULTS Mean ABC was similar in both cohort groups at the time of r and omization but became significantly higher ( decreased fear ) in the tai chi cohort at 8 months ( 57.9 vs 49.0 , P<.001 ) and at study end ( 59.2 vs 47.9 , P<.001 ) . After adjusting for covariates , the mean ABC after 12 months of intervention was significantly greater in the tai chi group than in the WE group , with the differences increasing with time ( mean difference at 12 months=9.5 points , 95 % confidence interval=4.8 - 14.2 , P<.001 ) . CONCLUSION Tai chi led to a significantly greater reduction in fear of falling than a WE program in transitionally frail older adults . The mean percentage change in ABC scores widened between tai chi and WE participants over the trial period . Tai chi should be considered in any program design ed to reduce falling and fear of falling in transitionally frail older adults Background Fibromyalgia ( FM ) , one of the most common musculoskeletal disorders , is associated with high levels of impaired health and inadequate or limited symptom relief . The cause of this complex syndrome is unknown , and there is no known cure . Numerous research results indicate that a combination of physical exercise and mind-body therapy is effective in symptom management . T’ai Chi , an ancient Chinese exercise , combines physical exercise with mind-body therapy . Purpose To investigate the effects of T’ai Chi exercise on FM symptoms and health-related quality of life . Design Pilot study , one group pre-to-post posttest design . Methods Participants with FM ( n = 39 ) formed a single group for 6 weeks of 1-hour , twice weekly T’ai Chi exercise classes . FM symptoms and health-related quality of life were measured before and after exercise . Findings Twenty-one participants completed at least 10 of the 12 exercise sessions . Although the dropout rate was higher than expected , measurements on both the Fibromyalgia Impact Question naire ( FIQ ) ( Buckhardt , Clark , & Bennett , 1991 ) and the Short Form-36 ( SF-36 ) ( Ware & Sherbourne , 1992 ) revealed statistically significant improvement in symptom management and health-related quality of life . Implication s for Nursing Research Knowledge of interventions to enhance health for the patient with mus Output:	Conclusions Tai Chi appears to be associated with improvements in psychological well-being including reduced stress , anxiety , depression and mood disturbance , and increased self-esteem .
MS21238	*TASK* the task is to summarize an input biomedical literature in six sentences *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 examined the effects of an 8-week exercise intervention on aerobic fitness , and roid and gynoid fat mass , and blood lipids in overweight and obese participants . Twenty-four sedentary participants ( average BMI = 30 ± 2 kg/m2 ; 18 females , 6 males ) were r and omized into either interval training and diet education ( INT group ) , continuous aerobic exercise and diet education ( CON group ) , or diet education only ( DIET group ) . Duration s of exercise sessions were similar ( ∼30 minutes ) , with both exercise groups completing the same amount of work . The INT and CON groups demonstrated significant improvements over time for ( p < 0.01 and p < 0.05 , ES = 1.1 and 1.2 , respectively ) and time to exhaustion on a grade d exercise test ( p < 0.01 and ES = 0.8 for both groups ) . Further , a large effect size ( 0.7 ) was recorded for the loss in and roid fat mass over time in the INT group only Regular exercise training is recognized as a powerful tool to improve work capacity , endothelial function and the cardiovascular risk profile in obesity , but it is unknown which of high-intensity aerobic exercise , moderate-intensity aerobic exercise or strength training is the optimal mode of exercise . In the present study , a total of 40 subjects were r and omized to high-intensity interval aerobic training , continuous moderate-intensity aerobic training or maximal strength training programmes for 12 weeks , three times/week . The high-intensity group performed aerobic interval walking/running at 85 - 95 % of maximal heart rate , whereas the moderate-intensity group exercised continuously at 60 - 70 % of maximal heart rate ; protocol s were isocaloric . The strength training group performed ' high-intensity ' leg press , abdominal and back strength training . Maximal oxygen uptake and endothelial function improved in all groups ; the greatest improvement was observed after high-intensity training , and an equal improvement was observed after moderate-intensity aerobic training and strength training . High-intensity aerobic training and strength training were associated with increased PGC-1alpha ( peroxisome-proliferator-activated receptor gamma co-activator 1alpha ) levels and improved Ca(2 + ) transport in the skeletal muscle , whereas only strength training improved antioxidant status . Both strength training and moderate-intensity aerobic training decreased oxidized LDL ( low-density lipoprotein ) levels . Only aerobic training decreased body weight and diastolic blood pressure . In conclusion , high-intensity aerobic interval training was better than moderate-intensity aerobic training in improving aerobic work capacity and endothelial function . An important contribution towards improved aerobic work capacity , endothelial function and cardiovascular health originates from strength training , which may serve as a substitute when whole-body aerobic exercise is contra-indicated or difficult to perform Background — Exercise training reduces the symptoms of chronic heart failure . Which exercise intensity yields maximal beneficial adaptations is controversial . Furthermore , the incidence of chronic heart failure increases with advanced age ; it has been reported that 88 % and 49 % of patients with a first diagnosis of chronic heart failure are > 65 and > 80 years old , respectively . Despite this , most previous studies have excluded patients with an age > 70 years . Our objective was to compare training programs with moderate versus high exercise intensity with regard to variables associated with cardiovascular function and prognosis in patients with postinfa rct ion heart failure . Methods and Results — Twenty-seven patients with stable postinfa rct ion heart failure who were undergoing optimal medical treatment , including & bgr;-blockers and angiotensin-converting enzyme inhibitors ( aged 75.5±11.1 years ; left ventricular [ LV ] ejection fraction 29 % ; & OV0312;o2peak 13 mL · kg−1 · min−1 ) were r and omized to either moderate continuous training ( 70 % of highest measured heart rate , ie , peak heart rate ) or aerobic interval training ( 95 % of peak heart rate ) 3 times per week for 12 weeks or to a control group that received st and ard advice regarding physical activity . & OV0312;o2peak increased more with aerobic interval training than moderate continuous training ( 46 % versus 14 % , P<0.001 ) and was associated with reverse LV remodeling . LV end-diastolic and end-systolic volumes declined with aerobic interval training only , by 18 % and 25 % , respectively ; LV ejection fraction increased 35 % , and pro-brain natriuretic peptide decreased 40 % . Improvement in brachial artery flow-mediated dilation ( endothelial function ) was greater with aerobic interval training , and mitochondrial function in lateral vastus muscle increased with aerobic interval training only . The MacNew global score for quality of life in cardiovascular disease increased in both exercise groups . No changes occurred in the control group . Conclusions — Exercise intensity was an important factor for reversing LV remodeling and improving aerobic capacity , endothelial function , and quality of life in patients with postinfa rct ion heart failure . These findings may have important implication s for exercise training in rehabilitation programs and future studies BACKGROUND Peak oxygen uptake ( Vo(2peak ) ) strongly predicts mortality in cardiac patients . We compared the effects of aerobic interval training ( AIT ) versus moderate continuous training ( MCT ) on Vo(2peak ) and quality of life after coronary artery bypass grafting ( CABG ) . METHODS Fifty-nine CABG patients were r and omized to either AIT at 90 % of maximum heart rate or MCT at 70 % of maximum heart rate , 5 d/wk , for 4 weeks at a rehabilitation center . Primary outcome was Vo(2peak ) , at baseline , after rehabilitation ( 4 weeks ) , and after 6 months of home-based exercise ( 6 months ) . RESULTS Vo(2peak ) increased between baseline and 4 weeks in AIT ( 27.1 + /- 4.5 vs 30.4 + /- 5.5 mL.kg(-1).min(-1 ) , P < .001 ) and MCT ( 26.2 + /- 5.2 vs 28.5 + /- 5.6 mL.kg(-1).min(-1 ) , P < .001 ; group difference , not significant ) . Aerobic interval training increased Vo(2peak ) between 4 weeks and 6 months ( 30.4 + /- 5.5 vs 32.2 + /- 7.0 mL.kg(-1).min(-1 ) , P < .001 ) , with no significant change in MCT ( 28.5 + /- 5.6 vs 29.5 + /- 5.7 mL.kg(-1).min(-1 ) ) . Quality of life improved in both groups from baseline to 4 weeks , remaining improved at 6 months . There were no changes in echocardiographic systolic and diastolic left ventricular function . Adiponectin increased between 4 weeks and 6 months in both groups ( group differences , not significant ) . CONCLUSIONS Four weeks of intense training increased Vo(2peak ) significantly after both AIT and MCT . Six months later , the AIT group had a significantly higher Vo(2peak ) than MCT . The results indicate that AIT and MCT increase Vo(2peak ) similarly in the short term , but with better long-term effect of AIT after CABG PURPOSE Autonomic dysfunction including sympathetic activation and vagal withdrawal has been reported in patients with chronic heart failure ( CHF ) . We tested the hypotheses that high-intensity interval exercise ( HIIE ) in CHF patients would enhance vagal modulation and thus decrease arrhythmic events . METHODS Eighteen CHF patients underwent a baseline assessment ( CON ) and were then r and omized to a single session of HIIE and to an isocaloric moderate-intensity continuous exercise ( MICE ) . We evaluated the HR , HR variability parameters , and arrhythmic events by 24-h Holter ECG recordings after HIIE , MICE , and CON sessions . RESULTS We found that HR was significantly decreased after HIIE ( 68 ± 3 bpm , P < 0.01 ) when compared with CON and MICE values ( 71.1 ± 2 and 69 ± 3 bpm , respectively ) . HIIE led to a significant increase in normalized high-frequency power ( 35.95 % ± 2.83 % vs 31.56 % ± 1.93 % and 24.61 % ± 2.62 % for CON and MICE , respectively , P < 0.01 ) . Both exercise conditions were associated with an increase in very low frequency power comparative to CON . After HIIE , premature ventricular contractions were significantly decreased ( 531 ± 338 vs 1007 ± 693 and 1671 ± 1604 for CON and MICE , respectively , P < 0.01 ) . An association was found between the changes in premature ventricular contraction and the changes in low-frequency/high-frequency ratio ( r = 0.66 , P < 0.01 ) in patients exposed to HIIE . CONCLUSION We demonstrate that a single session of HIIE improves autonomic profile of CHF patients , leading to significant reductions of HR and arrhythmic events in a 24-h posttraining period . Cardioprotective effects of HIIE in CHF patients need to be confirmed in a larger study population and on a long-term basis This study determined the cellular energetic and structural adaptations of elderly muscle to exercise training . Forty male and female subjects ( 69.2 + /- 0.6 yr ) were assigned to a control group or 6 mo of endurance ( ET ) or resistance training ( RT ) . We used magnetic resonance spectroscopy and imaging to characterize energetic properties and size of the quadriceps femoris muscle . The phosphocreatine and pH changes during exercise yielded the muscle oxidative properties , glycolytic ATP synthesis , and contractile ATP dem and . Muscle biopsies taken from the same site as the magnetic resonance measurements were used to determine myosin heavy chain isoforms , metabolite concentrations , and mitochondrial volume densities . The ET group showed changes in all energetic pathways : oxidative capacity ( + 31 % ) , contractile ATP dem and ( -21 % ) , and glycolytic ATP supply ( -56 % ) . The RT group had a large increase in oxidative capacity ( 57 % ) . Only the RT group exhibited change in structural properties : a rise in mitochondrial volume density ( 31 % ) and muscle size ( 10 % ) . These results demonstrate large energetic , but smaller structural , adaptations by elderly muscle with exercise training . The rise in oxidative properties with both ET and RT suggests that the aerobic pathway is particularly sensitive to exercise training in elderly muscle . Thus elderly muscle remains adaptable to chronic exercise , with large energetic changes accompanying both ET and RT Objective : To determine the effects of a 15-week high-intensity intermittent exercise ( HIIE ) program on subcutaneous and trunk fat and insulin resistance of young women . Design and procedures : Subjects were r and omly assigned to one of the three groups : HIIE ( n=15 ) , steady-state exercise ( SSE ; n=15 ) or control ( CONT ; n=15 ) . HIIE and SSE groups underwent a 15-week exercise intervention . Subjects : Forty-five women with a mean BMI of 23.2±2.0 kg m−2 and age of 20.2±2.0 years . Results : Both exercise groups demonstrated a significant improvement ( P<0.05 ) in cardiovascular fitness . However , only the HIIE group had a significant reduction in total body mass ( TBM ) , fat mass ( FM ) , trunk fat and fasting plasma insulin levels . There was significant fat loss ( P<0.05 ) in legs compared to arms in the HIIE group only . Lean compared to overweight women lost less fat after HIIE . Decreases in leptin concentrations were negatively correlated with increases in VO2peak ( r=−0.57 , P<0.05 ) and positively correlated with decreases in TBM ( r=0.47 ; P<0.0001 ) . There was no significant change in adiponectin levels after training . Conclusions : HIIE three times per week for 15 weeks compared to the same frequency of SSE exercise was associated with significant reductions in total body fat , subcutaneous leg and trunk fat , and insulin resistance in young women Background Increased aerobic exercise capacity appears to reduce both all-cause mortality and cardiovascular disease mortality . Physical exercise to improve peak oxygen uptake ( VO2peak ) is thus strongly recommended , however evidence regarding the most efficient training intensity for patients with coronary artery disease ( CAD ) is still lacking . The purpose of this r and omized study was therefore to assess the effects of high intensity aerobic interval exercise compared to moderate intensity exercise , representing the same total training load , for increasing VO2peak in stable CAD- patients . Methods Twenty-one stable CAD- patients were r and omized to supervised treadmill walking at either high intensity ( 80–90 % of VO2peak ) or moderate intensity ( 50–60 % of VO2peak ) three times a week for 10 weeks . Results After training VO2peak increased by 17.9 % ( P = 0.012 ) in the high intensity group and 7.9 % ( P = 0.038 ) in the moderate intensity group Output:	In spite of the method ological shortcomings of the primary studies included in the systematic review , we reasonably conclude that implementation of high intensity aerobic interval training in subjects with metabolic syndrome , leads to increases in peak oxygen consumption
MS21239	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: PURPOSE The aim of this prospect i ve study was to compare the sensitivity and specificity of sonography with those of MRI in evaluating epicondylitis . METHODS The affected elbows of 11 patients with suspected epicondylitis were examined sonographically , and the contralateral ( normal ) elbow was also examined for comparison . In 10 of these patients , the affected elbow was also examined with MRI . In addition , both elbows of 6 volunteers without epicondylitis were examined sonographically ; 1 elbow of each volunteer was design ated as the " test " elbow and was examined with MRI . The sonograms of the patients ' affected elbows and the volunteers ' test elbows were paired with the sonograms of the contralateral elbows for comparison and were r and omly shown twice to 2 readers . These readers , working independently and without knowledge of the findings of MRI , were instructed to state whether each elbow was normal or affected by epicondylitis . The MRI scans were then shown to the readers for similar review . RESULTS Sonographic features of epicondylitis included outward bowing of the common tendon , presence of hypoechoic fluid subadjacent to the common tendon , thickening , decreased echogenicity , and ill-defined margins of the common tendon . Sensitivity for detecting epicondylitis ranged from 64 % to 82 % for sonography and from 90 % to 100 % for MRI . Specificity ranged from 67 % to 100 % for sonography and from 83 % to 100 % for MRI . CONCLUSIONS Sonography is as specific but not as sensitive as MRI for evaluating epicondylitis . Used as an initial imaging tool , sonography might be adequate for diagnosing this condition in many patients , thus allowing MRI to be reserved for patients with symptoms whose sonographic findings are normal PURPOSE To determine the sensitivity and specificity of ultrasonography ( US ) in the detection of lateral epicondylitis and identify the US findings that are most strongly associated with symptoms . MATERIAL S AND METHODS Internal review board approval was obtained for retrospective review of the patient images , and the need for informed consent was waived . Internal review board approval was also obtained for scanning the 10 volunteers , all of whom gave informed consent . The study was compliant with the Health Insurance Portability and Accountability Act . US of the common extensor tendon was performed in 20 elbows in 10 asymptomatic volunteers ( six men , four women ; age range , 22 - 38 years ; mean age , 29.6 years ) and 37 elbows in 22 patients with symptoms of lateral epicondylitis ( 10 men , 12 women ; age range , 30 - 59 years ; mean age , 46 years ) . Fifty-seven representative images , one from each elbow , were r and omly assorted and interpreted by three independent readers who rated each common extensor tendon as normal or abnormal . Abnormal images were further classified as demonstrating one or more of eight US findings . Readers interpreted each image at two separate sessions to determine intrareader variability . The authors calculated the sensitivity and specificity of US in the diagnosis of lateral epicondylitis and the odds ratio for each US finding . Odds ratios were considered statistically significant at P < .05 when 95 % confidence intervals did not include one . RESULTS Sensitivities of US in the detection of symptomatic lateral epicondylitis ranged from 72 % to 88 % and specificities from 36 % to 48.5 % . Odds ratios for the following findings were statistically significant ( P < .05 ) for both reading sessions : calcification of common extensor tendon , tendon thickening , adjacent bone irregularity , focal hypoechoic regions , and diffuse heterogeneity . Odds ratios for lateral epicondyle enthesophytes were statistically significant ( P < .05 ) for the first reading session only . Odds ratios for linear intrasubstance tears and peritendinous fluid were not statistically significant . CONCLUSION US of the common extensor tendon had high sensitivity but low specificity in the detection of symptomatic lateral epicondylitis . The relationship between symptoms and intratendinous calcification , tendon thickening , adjacent bone irregularity , focal hypoechoic regions , and diffuse heterogeneity was statistically significant OBJECTIVES Following a consensus statement from a multidisciplinary UK workshop , a structured examination schedule was developed for the diagnosis and classification of musculoskeletal disorders of the upper limb . The aim of this study was to test the repeatability and the validity of the newly developed schedule in a hospital setting . METHOD 43 consecutive referrals to a soft tissue rheumatism clinic ( group 1 ) and 45 subjects with one of a list of specific upper limb disorders ( including shoulder capsulitis , rotator cuff tendinitis , lateral epicondylitis and tenosynovitis ) ( group 2 ) , were recruited from hospital rheumatology and orthopaedic outpatient clinics . All 88 subjects were examined by a research nurse ( blinded to diagnosis ) , and everyone from group 1 was independently examined by a rheumatologist . Between observer agreement was assessed among subjects from group 1 by calculating Cohen 's κ for dichotomous physical signs , and mean differences with limits of agreement for measured ranges of joint movement . To assess the validity of the examination , a pre-defined algorithm was applied to the nurse 's examination findings in patients from both groups , and the sensitivity and specificity of the derived diagnoses were determined in comparison with the clinic 's independent diagnosis as the reference st and ard . RESULTS The between observer repeatability of physical signs varied from good to excellent , with κ coefficients of 0.66 to 1.00 for most categorical observations , and mean absolute differences of 1.4 ° –11.9 ° for measurements of shoulder movement . The sensitivity of the schedule in comparison with the reference st and ard varied between diagnoses from 58%–100 % , while the specificities ranged from 84%–100 % . The nurse and the clinic physician generally agreed in their diagnoses , but in the presence of shoulder capsulitis the nurse usually also diagnosed shoulder tendinitis , whereas the clinic physician did not . CONCLUSION The new examination protocol is repeatable and gives acceptable diagnostic accuracy in a hospital setting . Examination can feasibly be delegated to a trained nurse , and the protocol has the benefit of face and construct validity as well as consensus backing . Its performance in the community , where disease is less clear cut , merits separate evaluation , and further refinement is needed to discriminate between discrete pathologies at the shoulder The histopathologic features from 11 patients who were treated surgically for lateral epicondylitis were grade d and compared to similar tissue from 12 cadaveric spec imens . All studies were done by a single pathologist who had no knowledge of the origin of the specimen . The surgical specimens were interpreted as abnormal in all 11 specimens , and all 12 of the control specimens were reported as being without histologic abnormality . Vascular proliferation was present in 10 of 11 and focal hyaline degeneration was recorded in all 11 of the surgical specimens . Neither feature was present in any of the control material ( P < 0.001 ) . These data suggest that chronic refractory lateral epicondylitis requiring sur gery is a degenerative rather than inflammatory proc ess . This may account for the lack of response to rest and antiinflammatory medication OBJECTIVE The purpose of this article is to evaluate prospect ively the utility of sonographic measurements of the common extensor tendon for diagnosing lateral epicondylitis . SUBJECTS AND METHODS Forty-eight patients with documented lateral epicondylitis and 63 healthy volunteers were enrolled and underwent ultrasound of the elbow joint . The common extensor tendon overlying the bony l and mark was scanned transversely , and the cross-section area and the maximum thickness were measured . Clinical examination was used as the reference st and ard in the diagnosis of lateral epicondylitis . Data from the patient and control groups were compared with established optimal diagnostic criteria for lateral epicondylitis using receiver operating characteristic curves . Qualitative evaluation with grayscale ultrasound was also performed on patients and healthy volunteers . RESULTS The common extensor tendon was significantly thicker in patients with lateral epicondylitis than in control subjects ( p < 0.01 ) . Tendon thickness greater than 4.2 mm ( sensitivity , 78.4 % ; specificity , 95.2 % ; accuracy , 87.7 % ) and area larger than or equal to 32 mm(2 ) ( sensitivity , 86.3 % ; specificity , 82.5 % ; accuracy , 84.2 % ) were highly predictive of lateral epicondylitis . For qualitative evaluation with gray-scale ultrasound , overall sensitivity , specificity , and accuracy values in the diagnosis of lateral epicondylitis were 76.5 % , 76.2 % , and 76.3 % , respectively . CONCLUSION The quantitative sonographic measurements had an excellent diagnostic performance for lateral epicondylitis , as well as good or excellent interreader agreement . A common extensor tendon cross-section area greater than or equal to 32 mm(2 ) and a thickness of 4.2 mm correlated well with the presence of lateral epicondylitis . However , further prospect i ve study is necessary to determine whether quantitative ultrasound with these cutoff values can improve the accuracy of the diagnosis of lateral epicondylitis OBJECTIVE Tennis elbow is a common complaint . Several treatment strategies have been described , but an optimal strategy has not been identified . Sonographic imaging as a predictive factor has never been studied . The aim of our study was to determine the value of sonographic findings in predicting response to conservative therapy for tennis elbow . This was done in a r and omized controlled trial in which the effectiveness of a brace only , physical therapy only , and a combination of both were compared . SUBJECTS AND METHODS Patients with tennis elbow complaints were r and omized . Sonography was performed before r and omization in 57 patients . Outcome measures at 6 weeks ' follow-up were success rate and decrease in pain ( scale , 0 - 100 ) . Data were analyzed using an intention-to-treat analysis . RESULTS In only 75 % of the imaged patients , sonographic abnormalities were identified and the clinical diagnosis could thus be confirmed . The following entities were identified : hypo- and hyperechogenicity , swelling , calcification , bursitis , enthesopathy , and tendinosis . The positive predictive value of sonography for the different entities varied between 0.78 and 0.82 , and the negative predictive value ranged between 0.23 and 0.71 . Predictive value was studied by subgroups of sonographic findings : hypoechoic , swelling present , enthesopathy , any entity present , and no entity present . We found no significant differences among the subgroups for either success rate ( range , 40 - 54 % ) or mean decrease in pain ( range , 16 - 28 percentage points ) . CONCLUSION No predictive value of sonography for the detection of abnormalities was identified in this study . Its diagnostic capability showed limited value . However , limitations in this study necessitate drawing definitive conclusions with care Output:	Based from the pooled sensitivity of abnormal ultrasound findings with homogenous results ( p > 0.05 ) , the hypoechogenicity of the common extensor origin has the best combination of diagnostic sensitivity and specificity . There is insufficient evidence supporting the use of Power Doppler Ultrasonogrophy , Real-time Sonoelastography and sonographic probe-induced tenderness in diagnosing LE . Conclusions The use of Gray-scale Ultrasonography is recommended in objective ly diagnosing lateral epicondylalgia . The presence of hypoechogenicity and bone changes indicates presence of a stressed common extensor origin-lateral epicondyle complex in elbows with lateral epicondylalgia . In addition to diagnosis , detection of these abnormal ultrasound findings allows localization of pathologies to tendon or bone that would assist in design ing an appropriate treatment suited to patient ’s condition
MS21240	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Epidemiologic studies have reported an association between major depression and smoking . This prospect i ve study examines the role of depression in smoking progression and cessation , and the role of smoking in first-onset major depression . METHODS Data are from a 5-year longitudinal epidemiologic study of 1007 young adults . Incidence and odds ratios ( ORs ) are based on the prospect i ve data . Hazards ratios are based on the combined lifetime data and estimated in Cox proportional hazards models with time-dependent covariates . RESULTS Based on the prospect i ve data , history of major depression at baseline increased significantly the risk for progression to daily smoking ( OR , 3.0 ; 95 % confidence interval , 1.1 - 8.2 ) , but did not decrease significantly smokers ' rate of quitting ( OR , 0.8 ; 95 % confidence interval , 0.4 - 1.6 ) . History of daily smoking at baseline increased significantly the risk for major depression ( OR , 1.9 ; 95 % confidence interval , 1.1 - 3.4 ) . These estimates were reduced somewhat when history of early ( ie , before age 15 years ) conduct problems was controlled . Estimates based on lifetime data were consistent with these results . CONCLUSIONS The observed influences from major depression to subsequent daily smoking and smoking to major depression support the plausibility of shared etiologies . Separate causal mechanisms in each direction might also operate , including self-medication of depressed mood as a factor in smoking progression and neuropharmacologic effects of nicotine and other smoke substances on neurotransmitter systems linked to depression Objective : Previous research has indicated an association between smoking and depression in adolescents , although the nature of the relationship is controversial . We sought to underst and this relationship better in a prospect i ve study by investigating whether there are sub population s of adolescents with different relationships between smoking and depressive symptoms . Methods : Our sample was 925 adolescents attending one of five Northern Virginia high schools , grade s 9 to 12 . We used General Growth Mixture Modeling as our method because it allowed identification and characterization of depressive symptoms trajectories and assessment of the effects of trajectory on 12th grade smoking . We defined the binary variable 12th grade current smoking as smoking on 1 or more of the past 30 days and more than 100 cigarettes smoked in a lifetime , versus not having smoked in the past 30 days . Results : We identified three trajectories : high , medium , and low depressive symptoms . For adolescents with high symptoms , 9th grade ( baseline ) smoking was associated with an overall deceleration of depressive symptoms , whereas for adolescents with moderate symptoms , baseline smoking was associated with an overall acceleration in depressive symptoms . Baseline smoking was not associated with rate of change in depressive symptoms for adolescents with low symptoms , nor was it associated with baseline depressive symptoms in any trajectory . Conclusion : These findings demonstrate that there is a relationship between smoking and depressive symptoms in adolescents , and that the relationship can vary by developmental trajectory , suggesting etiological heterogeneity . GGMM = General Growth Mixture Modeling ; CES-D = Center for Epidemiological Studies Depression ; GMM = Growth Mixture Modeling ; BIC = Bayesian Information Criterion ; LMR LRT = Lo-Mendell-Rubin Likelihood Ratio ; OR = odds ratio ; CI = confidence interval Although it has been hypothesized that depressive persons have an excess risk of cancer , few prospect i ve data are available . The association between depressiveness and subsequent incidence of lung cancer was studied in the nationally representative Mini-Finl and Health Survey . The study population comprised 7,018 adult men and women , free from cancer at the baseline , carried out in 1978 - 1980 . During a 14-year follow-up , 605 cancer cases occurred , of which 70 were male lung cancer patients . Mental problems and disorders were assessed at the baseline examination using st and ard interview techniques ( General Health Question naire and Present State Examination ) . The relative risk of lung cancer between depressive persons and individuals with a normal depressiveness score was 3.32 ( 95 % confidence interval 1.53 - 7.20 ) . Neither adjustment for the potential confounding factors of age , education , geographic area , smoking , alcohol consumption , body mass index , serum cholesterol , leisure-time exercise , general health , and use of antidepressant medication nor exclusion of cancer cases occurring during the first 4 years of follow-up notably altered the results . There was a strong interaction between depressiveness and smoking . The relative risks of lung cancer between smokers and nonsmokers were 3.38 ( 95 % confidence interval 1.09 - 10.52 ) at normal depressiveness score levels and 19.67 ( 95 % confidence interval 2.57 - 150.7 ) at strongly elevated levels , respectively . It is possible that depressiveness modifies the effect of smoking on lung cancer risk either by biologic mechanisms or by affecting smoking behavior Smokers have a higher prevalence of major depressive episodes and depressive symptoms than the general population , but whether this association is causal , or is due to confounding or reverse causation is uncertain because of the problems inherent in some epidemiological studies . Mendelian r and omization , in which a genetic variant is used as a surrogate for measuring exposure , is an approach which may be used to better underst and this association . We investigated the rs1051730 single nucleotide polymorphism in the nicotine acetylcholine receptor gene cluster ( CHRNA5-CHRNA3-CHRNB4 ) , associated with smoking phenotypes , to determine whether women who continued to smoke were also more likely to report a low mood during pregnancy . We found among women who smoked pre-pregnancy , those with the 1051730 T allele smoked more and were less likely to quit smoking during pregnancy , but were also less likely to report high levels of depressed mood at 18 weeks of pregnancy ( per allele OR = 0.84 , 95%CI 0.72 to 0.99 , p = 0.034 ) . The association between genotype and depressed mood was limited to women who were smokers prior to pregnancy , with weak evidence of an interaction between smoking status and genotype ( p = 0.07 ) . Our results do not support a causal role of smoking on depressed mood , but are consistent with a self-medication hypothesis , whereby smoking is used to alleviate symptoms of depression . A replication study using multiple genetic variants which influence smoking via different pathways is required to confirm these findings and provide evidence that the genetic variant is reflecting the effect of quitting smoking on depressed mood , and is not directly affecting mood INTRODUCTION Smoking research and intervention efforts have neglected older women . Depressive symptoms , which are common in middle-aged and older women , are related to the maintenance of adult smoking . METHODS This study investigated the relation of a composite measure of current depressive symptoms , derived from a short form of the Center for Epidemiological Studies Depression Scale , and history of depressive symptoms , derived from two items from the Diagnostic Interview Schedule , to smoking outcomes in the Women 's Health Initiative Observational Study ( N = 90,627 ) . Participants were postmenopausal with an average age of 63.6 years at baseline . Participants were recruited from urban , suburban , and rural areas surrounding 40 clinical centers in the United States . Analyses controlled for age , educational level , and ethnicity . RESULTS In multinomial logistic regression analyses , depressive symptoms were related cross-sectionally to current light ( odds ratio [ OR ] = 1.19 , 95 % CI = 1.14 - 1.23 ) and heavier ( OR = 1.28 , 95 % CI = 1.23 - 1.32 ) smoking at baseline compared with nonsmokers . In prospect i ve multiple logistic regression analyses , baseline depressive symptoms were negatively predictive of smoking cessation at a 1-year follow-up ( OR = .85 , 95 % CI = 0.77 - 0.93 ) and at participants ' final assessment s in the study ( OR = .92 , 95 % CI = 0.85 - 0.98 ) . Light smokers had more than 2 times higher odds of smoking cessation than did heavier smokers . CONCLUSIONS The present findings demonstrate a consistent link between depressive symptoms and negative smoking-related behaviors among middle-aged and older women at both light and heavier smoking levels Using data from a 4-wave longitudinal study with a school-based sample of 1,218 middle adolescents , the authors investigated the directionality ( e.g. , unidirectionality and bidirectionality ) of the prospect i ve relationship between depressive symptoms and cigarette use within the context of potential confounding variables and common and unique intrapersonal and interpersonal predictors . Findings indicated that serious and persistent depressive symptoms were prospect i ve predictors of increased cigarette use across time , after controlling for baseline levels of smoking . Similarly , heavy and persistent smoking prospect ively predicted increases in depressive symptoms . Intrapersonal and interpersonal predictors of cross-temporal changes in depressive symptoms and cigarette use were more unique than common . Latent growth curve modeling indicated a quadratic trend in adolescent cigarette smoking across time with an initial acceleration followed by a deceleration , though there was substantial intraindividual variation in individual trajectories OBJECTIVE This study aim ed to develop a simple risk table of modifiable factors prospect ively associated with depression in later life that could be used to guide the assessment , management and introduction of preventive strategies in clinical practice . METHODS This retrospective cohort study included 4636 men aged 65 to 83 years living in the community who denied history of past diagnosis or treatment for depression . They self-reported information about their physical activity , weight and height , smoking history , alcohol consumption and dietary habits , as well as history of hypertension , diabetes , coronary heart disease and stroke . We calculated the body mass index ( BMI ) in kg/m(2 ) . Three to 8 years later they were assessed with the Geriatric Depression Scale 15 ( GDS-15 ) and those with a total score of 7 or greater were considered to display clinical ly significant symptoms of depression . We used binomial exponentiated log-linked general linear models to estimate the risk ratio ( RR ) and 95 % confidence interval ( 95 % CI ) of incident depression after adjusting for age , education , marital status and prevalent medical illnesses . We calculated the probability of depression for each individual combination of risk factors and displayed the results in a risk table . RESULTS Two hundred and twenty-nine men ( 4.5 % ) showed evidence of incident depression 5.7±0.9 ( mean±st and ard deviation ) years later . Measured dietary factors showed no association with incident depression . The probability of depression was the highest for older men who were underweight , overweight or obese , physically inactive , risk drinkers and smokers ( 12.0 % , 95 % CI=7.0 % , 17.1 % ) , and the lowest for those who had all 4 healthy lifestyle markers : physically active , normal body mass , non-risk drinking and non-smoking ( 1.6 % , 95 % CI=0.6 % , 2.5 % ) . The probability of incident depression fell between these two extremes for different combinations of lifestyle practice s. CONCLUSION Four modifiable lifestyle factors can be used in combination to produce a risk table that predicts the probability of incident depression over a period of 3 to 8 years . The risk table is simple , informative and can be easily incorporated into clinical practice to guide assessment and risk reduction interventions BACKGROUND The aim of the present study was to investigate the stability and longitudinal association between depression and smoking status within a community sample with type 2 diabetes ( T2D ) while controlling for sociodemographic and disease-related variables . METHODS Adults with T2D were recruited and agreed to be followed-up via r and om digit dialing for the Montreal Diabetes Health Study . At baseline , 1614 individuals were classified as never ( n = 592 ) , former ( n = 690 ) , light ( ≤10 cigarettes a day ; n = 128 ) and moderate-heavy ( 11 + cigarettes a day ; n = 204 ) smokers . Depression was assessed using the Patient Health Question naire-9 and individuals were classified as either " none " or having depression syndrome . Generalized estimating equations were used to test the association between depression syndrome and current smoking status while controlling for other demographic and health-related variables . RESULTS Prevalence rates of smoking and depression showed mild to substantial agreement over time . Depression syndrome was significantly associated with moderate-heavy smoking in the fully adjusted model using cross-sectional ( all four waves ; odds ratio [ OR ] 1.46 ; 95 % confidence interval [ CI ] 1.08 - 1.99 ; P < 0.05 ) and longitudinal ( controlling for depression at baseline ; OR 1.54 ; 95 % CI 1.02 - 2.31 ; P < 0.05 ) data . CONCLUSIONS Smoking and depression prevalence rates appear to be stable over time in our community sample with T2D . Moderate-heavy smoking is strongly associated with elevated depression , both in cross-sectional and longitudinal models . Persistent moderate-heavy smokers may be at increased risk of both physical and mental health complications . This burden is even greater for those with T2D Both Output:	Overall , nearly half the studies reported that baseline depression/anxiety was associated with some type of later smoking behavior , while over a third found evidence that a smoking exposure was associated with later depression/anxiety . The results varied considerably , with evidence for smoking both associated with subsequent depression and anxiety , and vice versa . Suggesting that despite advantages of longitudinal studies , they can not alone provide strong evidence of causality .
MS21241	*TASK* the task is to summarize an input biomedical literature in six sentences *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 prospect i ve , r and omized study was to compare ovarian response and oocyte and embryo yields in women undergoing ovulation induction for IVF/ICSI using recombinant human FSH ( rhFSH ) alone or in combination with recombinant human LH ( rhLH ) . METHODS Patients were r and omized to receive rhFSH alone ( group F ; n = 13 ) or rhFSH + rhLH ( group L ; n = 15 ) . rhFSH was administered according to a step-down protocol ; patients assigned to group L received rhLH at a fixed dose of 75 IU ( 1 ampoule ) throughout the treatment period . RESULTS The total dose of rhFSH , number of growing follicles , and serum concentrations of estradiol ( E2 ) on the day of hCG administration were similar in both treatment groups . However , the percentage of metaphase II oocytes and fertilization rate were significantly higher in group F than in group L. The lower fertilization rates associated with rhLH were also seen in a subgroup of patients from group L who had undergone a previous ART cycle stimulated with FSH only and thus acted as their own controls . However , when in vitro fertilization ( IVF ) and intracytoplasmic sperm injection cycles were considered separately , differences in fertilization rates were statistically significant only for oocytes treated by conventional IVF . CONCLUSIONS This study shows that the addition of recombinant LH to recombinant FSH in pituitary-suppressed women undergoing ART does not improve the ovarian response and even may have a negative impact on oocyte maturation and fertilization OBJECTIVE To evaluate the effects of recombinant human luteinizing hormone ( rhLH ) supplementation on ovarian stimulation and implantation rate in down-regulated women of advanced reproductive age . DESIGN Prospect i ve r and omized study . SETTING University teaching hospital . PATIENT(S ) A total of 120 consecutive normogonadotropic infertile women > or = 35 years old undergoing their first cycle of IVF or intracytoplasmic sperm injection ( ICSI ) treatment . INTERVENTION(S ) Ovarian stimulation in a long agonist protocol with a combination of recombinant human follicle-stimulating hormone ( rhFSH ) and rhLH ( group 1 , n = 60 ) starting on day 6 of FSH stimulation until hCG at a daily fixed dose of 150 IU of rhLH , or with rhFSH alone ( group 2 , n = 60 ) . MAIN OUTCOME MEASURE(S ) Ovarian stimulation characteristics , ovum retrieval , and IVF/ICSI outcome . RESULT ( S ) The mean number of intermediate ( 10 - 14 mm ) and large ( > 14- < 18 mm ) but not leading ( > or = 18 mm ) follicles was significantly lower in group 1 on the day of hCG injection . The oocyte yield and maturity as well as the number of oocytes fertilized were significantly higher in group 2 than in group 1 . However , the number of patients having embryo transfer ( n = 55 in both treatment groups ) , the number and quality of embryos replaced , the implantation rate ( 20.6 % vs. 21.7 % ) and clinical pregnancy rates per embryo transfer ( 44 % vs. 45 % ) were similar in groups 1 and 2 . CONCLUSION ( S ) The rhLH supplementation does not increase ovarian response and implantation rates in patients of older reproductive age stimulated with rhFSH under pituitary suppression for assisted reproductive technologies ( ARTs ) Women undergoing intracytoplasmic sperm injection ( ICSI ) for male factor infertility were r and omly assigned to receive ovarian stimulation in a long agonist protocol with a combination of recombinant human FSH ( r-hFSH ; Gonal-F ) and recombinant human LH ( r-hLH ; Luveris ) ( n = 212 ) starting on day 6 of FSH stimulation until human chorionic gonadotrophin ( HCG ) at a daily fixed dose of 150 IU r-hLH , or with r-hFSH alone ( n = 219 ) . There was no significant difference in the number of metaphase II oocytes retrieved ( 10.3 versus 10.4 ) in patients treated with r-hFSH and r-hLH versus r-hFSH alone ; however , more embryos were transferred in the LH-supplemented group ( 2.9 versus 2.8 , P = 0.037 ) . Overall , the implantation rates were 22.9 versus 27.0 % in patients treated with r-hFSH and r-hLH versus with r-hFSH alone respectively ( NS ) . The respective numbers of MII oocytes retrieved in patients < 35 or > or=35 years were 11 versus 8.3 ( P = 0.010 ) for patients treated with r-hFSH alone , and 10.7 versus 9.3 ( NS ) for those given supplemental r-hLH ( 150 IU ) from day 6 . Implantation rates in patients < 35 years treated with r-hFSH were higher ( 30.7 % ) than those receiving r-hFSH and r-hLH , ( 23.5 % ) ( P = 0.068 ) . In patients > or=35 years , the implantation rates were 21.7 % for those patients supplemented with 150 IU r-hLH from day 6 of stimulation versus 15.7 % when treated with FSH alone ( NS ) . Younger patients therefore do not seem to benefit from an LH-supplemented ovarian stimulation protocol , but women > or=35 years undergoing assisted reproduction may benefit from using r-hLH in addition to r-hFSH BACKGROUND Poor ovarian response is a common clinical problem , affecting up to 26 % of IVF cycles . For these women , addition of recombinant luteinizing hormone ( rLH ) to ovarian hyperstimulation with recombinant FSH has a beneficial effect on ongoing pregnancy rates , but its effect on the yield of top- quality embryos is unknown . METHODS We conducted a r and omized controlled trial in women expected to respond poorly under ovarian hyperstimulation during their first IVF cycle [ all women aged 35 - 41 and women with FSH > 12 IU/ml and antral follicle count ( AFC ) ≤ 5 ] . Women were r and omly allocated to rFSH and rLH ( 2:1 ratio ) or rFSH alone ( control group ) after down-regulation with a GnRH agonist . The primary outcome was the proportion of top- quality embryos per woman on the day of transfer . Secondary outcomes were the number of stimulation days , the number of follicles ≥17 mm , the number of oocytes , the fertilization rate , the number of embryos , the number of women with ≥1 top- quality embryo , the biochemical , clinical and ongoing pregnancy rates and the miscarriage rate . RESULTS There were 116 women allocated to the rLH group and 128 allocated to the control group . The proportion of top- quality embryos per woman was 17 % in the rLH group and 11 % in the control group [ mean difference 0.06 ; 95 % confidence interval ( CI ) -0.01 - 0.14 ] . In the rLH and control groups respectively , 47 ( 41 % ) and 41 ( 32 % ) women had at least one top- quality embryo on the day of transfer ( relative risk : 1.3 , 95 % CI 0.91 - 1.77 ) . The ongoing pregnancy rate was 13 versus 12 % ( relative risk : 1.1 ; 95 % CI 0.57 - 2.16 ) for the rLH group compared with the control group . CONCLUSIONS This study found no significant difference in embryo quality after the addition of rLH to rFSH for ovarian stimulation in women with poor ovarian reserve . CLINICAL TRIALS IDENTIFIER NTR1457 This single-centre , r and omized , parallel group , comparative study aim ed to identify potential benefits of mid-follicular recombinant human LH ( r-HLH ) supplementation in women aged 35 - 39 years undergoing ovarian stimulation for intracytoplasmic sperm injection ( ICSI ) . The main endpoint was the number of metaphase II oocytes retrieved . After pituitary suppression with a gonadotrophin-releasing hormone agonist , ovarian stimulation was initiated with recombinant human FSH ( r-HFSH ; 300 - 450 IU/day ) . On stimulation day 6 , patients were r and omized to receive r-HFSH alone or r-HFSH + r-HLH ( r-HLH 150 IU/day ) for the remainder of the stimulation period . Final follicular maturation was triggered with 250 mug of recombinant human chorionic gonadotrophin . After assessing oocyte nuclear maturity , oocyte were fertilized by ICSI and afterwards embryo quality was analyzed . Of the 131 women enrolled , 68 were allocated to r-HFSH alone and 63 to r-HFSH + r-HLH . No significant differences were observed in markers of either oocyte or embryo quality or quantity . However , higher rates of implantation and live birth per started cycle were observed with r-HLH supplementation than with r-HFSH alone . Although additional large studies are required to further investigate these findings , r-HLH supplementation for women aged 35 - 39 years undergoing ICSI is recommended as it may have a beneficial action on implantation BACKGROUND In approximately 12 - 14 % of young normogonadotrophic women treated with a depot GnRH agonist long protocol , the initial ovarian response to recombinant human FSH ( rFSH ) can be suboptimal . We have tested the hypothesis that these women may benefit from recombinant human LH ( rLH ) supplementation in a multicentre , prospect i ve , r and omized trial compared with patients treated with an rFSH step-up protocol . METHODS A total of 260 young normogonadotrophic women undergoing controlled ovarian stimulation with a GnRH agonist long protocol for IVF/ICSI were enrolled . The starting dose of rFSH was 225 IU . One hundred and thirty patients with serum estradiol levels < 180 pg/ml and with at least six follicles with a mean diameter > 5 mm but none > 10 mm on both day 5 and day 8 of stimulation were r and omly allocated to two groups . From the eighth day of stimulation , women in group A ( n=65 ) received 150 IU of rLH in addition to rFSH , while those in group B ( n=65 ) had an increase of 150 IU in the daily dose of rFSH ( step-up protocol ) . One hundred and thirty normally responding women continued monotherapy with rFSH and served as a further control population ( group C ) . RESULTS The mean number of cumulus-oocyte complexes retrieved in group A ( 9.0+/-4.3 ) was significantly higher ( P<0.01 ) compared with group B ( rFSH 6.1+/-2.6 ) but significantly lower compared with group C ( 10.49+/-3.7 , P<0.05 ) . Implantation and pregnancy rates were significantly lower ( P<0.05 ) in the rFSH step-up group ( 10.5 and 29.3 % respectively ) when compared with normal responders ( 18.1 and 47.3 % respectively ) . CONCLUSIONS rLH supplementation is more effective than increasing the dose of rFSH in terms of ovarian outcome in patients with an initial inadequate ovarian response to rFSH alone BACKGROUND The effect of recombinant human LH ( r-hLH ; lutropin alfa ) in women undergoing controlled ovarian stimulation with recombinant human FSH ( r-hFSH ) prior to IVF was investigated . METHODS After down-regulation with the GnRH agonist , buserelin , 114 normo-ovulatory women ( aged 18 - 37 years ) received r-hFSH alone until the lead follicle reached a diameter of 14 mm . Patients were then r and omized in a double-blind fashion to receive r-hFSH in addition to r-hLH , 75 IU s.c . , or placebo daily for a maximum of 10 days prior to oocyte retrieval and IVF . The primary end-point was the number of metaphase II oocytes . RESULTS There were no significant differences between treatment groups for the primary end-point . Serum estradiol concentrations on the day of HCG administration were significantly higher in the group receiving r-hLH plus r-hFSH than in the group receiving r-hFSH alone ( P = 0.0001 ) , but there were no significant differences between the groups in dose and duration of r-hFSH treatment required , oocyte maturation , fertilization rate , pregnancy rate and live birth rate . CONCLUSION In this patient population , the addition of r-hLH during the late follicular phase of a long GnRH agonist and r-hFSH stimulation cycle provides no further benefit in terms of oocyte maturation or other end-points OBJECTIVE To prospect ively assess the effect of using a combination of recombinant follicle-stimulating hormone ( rFSH ) and recombinant luteinizing hormone ( rLH ) on ovarian stimulation parameters and treatment outcome among poor-responder patients . DESIGN Prospect i ve r and omized trial . SETTING University-associated private medical center . P Output:	In conclusion , this meta- analysis suggests that the addition of r-hLH to r-hFSH may be beneficial for women with POR
MS21242	*TASK* the task is to summarize an input biomedical literature in six sentences *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 , a condition predominantly affecting the elderly , represents an ever-increasing clinical and financial burden for the NHS . Cardiac rehabilitation , a service that incorporates patient education , exercise training and lifestyle modification , requires further evaluation in heart failure management . AIM The aim of this study was to determine whether a cardiac rehabilitation programme improved on the outcomes of an outpatient heart failure clinic ( st and ard care ) for patients , over 60 years of age , with chronic heart failure . METHODS Two hundred patients ( 60 - 89 years , 66 % male ) with New York Heart Association ( NYHA ) II or III heart failure confirmed by echocardiography were r and omised . Both st and ard care and experimental groups attended clinic with a cardiologist and specialist nurse every 8 weeks . Interventions included exercise prescription , education , dietetics , occupational therapy and psychosocial counselling . The main outcome measures were functional status ( NYHA , 6-min walk ) , health-related quality of life ( MLHF and EuroQol ) and hospital admissions . RESULTS There were significant improvements in MLHF and EuroQol scores , NYHA classification and 6-min walking distance ( meters ) at 24 weeks between the groups ( p<0.001 ) . The experimental group had fewer admissions ( 11 vs. 33 , p<0.01 ) and spent fewer days in hospital ( 41 vs. 187 , p<0.001 ) . CONCLUSIONS Cardiac rehabilitation , already widely established in the UK , offers an effective model of care for older patients with heart failure IN THE EARLY 1890S , DR WILLIAM HALSTED DEVELOPED radical mastectomy for breast cancer . Surgeons performed the Halsted procedure for more than 80 years even though there was little systematic evidence for its success . Then a new breed of scholars subjected the procedure to formal methods of evaluation unknown to Halsted . The methods —r and omized controlled trials ( RCTs ) principal among them — led to a surprise : radical mastectomy had no advantage over simpler forms of treatment . This is but 1 example of the hard-won victory of evidence over belief in medicine . The pioneers of the formal evaluation of medical practice s raised questions that traditional practitioners did not welcome . But in time , formal evaluation prevailed . The pioneers developed a hierarchy of evidentiary rigor relating the design of a study to the confidence that could be placed in the findings , from the lowly , nearly valueless anecdote to the royalty of evidence , the RCT . Concurrently , a similar story of hard-won learning unfolded in the so-called quality movement . Scholars illuminated the scale and types of defects in the processes of care and the outcomes , including high rates of unscientific care , inappropriate care , geographic variations in practice , latent disagreements among specialists , and oftenunrecognized medical injury to patients . Like the pioneers of evidence -based medicine , students of medical quality were at first largely ignored , but no longer . In 1999 and 2001 , the Institute of Medicine published 2 l and mark reports on the evidence for quality failures and called urgently for re design of care systems to achieve improvements . The story could end here happily with 2 great streams of endeavor merging into a framework for conjoint action : improving clinical evidence and improving the process of care . Instead , the 2 endeavors are often in unhappy tension . Neither disputes that progress toward health care ’s main goal , the relief of illness and pain , requires research of many kinds : basic , clinical , systems , epidemiologic . The disagreement centers on epistemology — ways to get at “ truth ” and how those ways should vary depending on the knowledge sought . Individuals most involved in day-to-day improvement work fear that if “ evidence ” is too narrowly defined and the approach to gathering evidence too severely constrained , progress may be the victim . For example , the RCT is a powerful , perhaps unequaled , research design to explore the efficacy of conceptually neat components of clinical practice —tests , drugs , and procedures . For other crucially important learning purpose s , however , it serves less well . Recent controversies about the evaluation of rapid response teams provide a case in point . These controversies show the importance of adjusting research methods to fit research questions . Although only 10 % to 15 % of in patients resuscitated outside intensive care units survive to hospital discharge , early warning signs are present in a large percentage of patients who ultimately experience cardiac arrest . Rapid response team systems bring expert clinicians to the bedsides of deteriorating patients before arrest occurs . In the mid 1990s , based largely on reports from Australian investigators , the Institute for Healthcare Improvement and others began introducing the concept to willing hospitals . Local experience strongly suggested that these systems often , although not always , were associated with improved outcomes , including reduced anxiety among nursing staff ; increased interdisciplinary teamwork ; decreased cardiac arrests outside of intensive care units ; and , in some cases , declines in mortality . The evidence base took a turn in June 2005 with the publication of the Medical Early Response Intervention and Therapy ( MERIT ) Study , a cluster r and omized prospect i ve trial that cl aim ed to find no beneficial effect of these teams on several primary outcomes . Controversy has continued since then regarding the scientific evidence for rapid response systems . In fact , the MERIT trial was not negative ; it was inconclusive . The study team encountered an array of serious problems in execution , common in social science . For example , although the study ’s power calculation assumed a baseline rate of 30 events per 1000 admissions , the actual rate proved to be fewer than 7 events per 1000 admissions ; thus , the study was ef fect ively underpowered by 500 % . Crosscontamination abounded ; some control hospitals implemented rapid response protocol s , and several study Background . The growing number of patients with congestive heart failure has increased both the pressure on hospital re sources and the need for community management of the condition . Improving hospital-to-home transition for this population is a logical step in responding to current practice guidelines ’ recommendations for coordination and education . Positive outcomes have been reported from trials evaluating multiple interventions , enhanced hospital discharge , and follow-up through the addition of a case management role . The question remains if similar gains could be achieved working with usual hospital and community nurses . Methods . A 12-week , prospect i ve , r and omized controlled trial was conducted of the effect of transitional care on health-related quality of life ( disease-specific and generic measures ) , rates of readmission , and emergency room use . The nurse-led intervention focused on the transition from hospital-to-home and supportive care for self-management 2 weeks after hospital discharge . Results . At 6 weeks after hospital discharge , the overall Minnesota Living with Heart Failure Question naire ( MLHFQ ) score was better among the Transitional Care patients ( 27.2 ± 19.1 SD ) than among the Usual Care patients ( 37.5 ± 20.3 SD;P = 0.002 ) . Similar results were found at 12 weeks postdischarge for the overall MLHFQ and at 6- and 12-weeks postdischarge for the MLHFQ ’s Physical Dimension and Emotional Dimension subscales . Differences in generic quality life , as assessed by the SF-36 Physical component , Mental Component , and General Health subscales , were not significantly different between the Transition and Usual Care groups . At 12 weeks postdischarge , 31 % of the Usual Care patients had been readmitted compared with 23 % of the Transitional Care patients ( P = 0.26 ) , and 46 % of the Usual Care group visited the emergency department compared with 29 % in the Transitional Care group ( & khgr;2 = 4.86 , df 1 , P = 0.03 ) . Conclusions . There were significant improvements in health-related quality of life ( HRQL ) associated with Transitional Care and less use of emergency rooms BACKGROUND We examined the effect of a home-based intervention ( HBI ) on readmission and death among " high-risk " patients with congestive heart failure discharged home from acute hospital care . METHODS Hospitalized patients with congestive heart failure and impaired systolic function , intolerance to exercise , and a history of 1 or more hospital admissions for acute heart failure were r and omized to either usual care ( n=48 ) or HBI at 1 week after discharge ( n=49 ) . Home-based intervention comprised a single home visit ( by a nurse and pharmacist ) to optimize medication management , identify early clinical deterioration , and intensify medical follow-up and caregiver vigilance as appropriate . The primary end point of the study was frequency of unplanned readmissions plus out-of-hospital deaths within 6 months of discharge . Secondary end points included duration of hospital stay and overall mortality . RESULTS During follow-up , patients in the HBI group had fewer unplanned readmissions ( 36 vs 63 ; P=.03 ) and fewer out-of-hospital deaths ( 1 vs 5 ; P=.11 ) : 0.8+/-0.9 vs 1.4+/-1.8 ( mean + /- SD ) events per patient assigned to HBI and usual care , respectively ( P=.03 ) . Patients in the HBI group also had fewer days of hospitalization ( 261 vs 452 ; P=.05 ) and fewer total deaths ( 6 vs 12 ; P=.11 ) . Patients assigned to usual care were more likely to experience 3 or more readmissions for acute heart failure ( P=.02 ) . Predictors of unplanned readmission were ( 1 ) 14 days or more of unplanned readmission during the 6 months before study entry ( odds ratio [ OR ] , 5.2 ; 95 % confidence interval [ CI ] , 1.8 - 16.2 ) , ( 2 ) previous admission for acute myocardial ischemia ( OR , 3.3 ; 95 % CI , 1.2 - 9.1 ) , and ( 3 ) an albumin plasma concentration of 38 g/L or less ( OR , 2.4 ; 95 % CI , 1.2 - 6.0 ) . Home-based intervention was also associated with a trend toward reduced risk of unplanned readmission ( OR , 0.4 ; 95 % CI , 0.2 - 1.1 ) . CONCLUSION Among a cohort of high-risk patients with congestive heart failure , HBI was associated with reduced frequency of unplanned readmissions plus out-of-hospital deaths within 6 months of discharge from the hospital Despite efforts to improve the discharge planning process and subsequent outcomes , existing mechanisms fail to accurately identify elders ' needs for follow-up care . Studies report rehospitalization rates ranging from 12 to 50 % . The two aims of this study were to ( 1 ) examine the difference in outcomes for elders hospitalized with heart failure and caregivers who participated in a professional-patient partnership model of discharge planning compared to those who received the usual discharge planning and ( 2 ) examine differences in costs associated with hospital readmission and use of the emergency room following hospital discharge . A before- and -after nonequivalent control group design was used for this study . Data were collected from the control and the intervention cohorts before discharge and at 2 weeks and 2 months postdischarge . One hundred and fifty-eight patient-caregiver dyads completed both the predischarge and 2-weeks postdischarge interviews ; 140 also completed a 2-month follow up . The average age of elders was 73.7 years ; the average age of the caregivers was 58.5 years . The findings indicated that elders in the intervention cohort felt more prepared to manage care , reported more continuity of information about care management and services , felt they were in better health , and when readmitted spent fewer days in the hospital than the control cohort . Caregivers in the intervention cohort also reported receiving more information about care management and having a more positive reaction to caregiving 2 weeks postdischarge than the control cohort AIMS To determine the effect of an integrated heart failure management programme , involving patient and family , primary and secondary care , on quality of life and death or hospital readmissions in patients with chronic heart failure . METHODS AND RESULTS This trial was a cluster r and omized , controlled trial of integrated primary / secondary care compared with usual care for patients with heart failure . The intervention involved clinical review at a hospital-based heart failure clinic early after discharge , individual and group education sessions , a personal diary to record medication and body weight , information booklets and regular clinical follow-up alternating between the general practitioner and heart failure clinic . Follow-up was for 12 months . One hundred and ninety-seven patients admitted to Auckl and Hospital with an episode of heart failure were enrolled in the study . There was no significant difference between the intervention and control groups for the combined end-point of death or hospital readmission . The physical dimension of quality of life showed a greater improvement in the intervention group from baseline to 12 months compared with the control group ( -11.1 vs -5.8 respectively , 2 P=0.015 ) . The main effect of the intervention was attributable to the prevention of multiple admissions ( 56 intervention group vs 95 control group , 2 P=0.015 ) and associated reduction in bed days . CONCLUSIONS This integrated management programme for patients with chronic heart failure improved quality of life and reduced total hospital admissions and total bed days BACKGROUND Despite the availability of proven therapies , outcomes in patients with heart failure ( HF ) remain poor . In this 2-stage , multicenter trial , we evaluated the effect of a disease management program on clinical and economic outcomes in patients with HF . METHODS AND RESULTS In Stage 1 , a pharmacist or nurse assessed each patient and made recommendations to the physician to add or adjust angiotensin-converting enzyme ( ACE ) inhibitors and other HF medications . Before discharge ( Stage 2 ) , patients were r and omized to a patient support program ( PSP ) ( education about HF , self-monitoring , adherence aids , newsletters , tele Output:	We could not explain the considerable differences in hospitalization and quality of life across the studies . Chronic care management significantly reduces mortality . Positive effects on hospitalization and quality of life were shown , however , with substantial heterogeneity in effectiveness . This heterogeneity is not explained by study quality , length of follow-up , or the number of chronic care model components .
MS21243	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Based on the two legal st and ards of informed consent currently in use , the Medical Practice St and ard and the Reasonable Person St and ard , two disclosures containing information about the risks and benefits of the anticonvulsant , Carbamazepine , were empirically derived . One of these two disclosures was r and omly given to a sample of 39 seizure patients and the parents of pediatric seizure patients prescribed this drug . Subjects were interviewed either immediately after disclosure and at followup , or at followup only . The results provide no evidence for the hypothesized negative effects — anxiety , treatment refusal , reduced compliance and increased side effects — of providing patients with extensive disclosures about prescription drugs Objective : To determine whether the use of verbal descriptors suggested by the European Union ( EU ) such as “ common ” ( 1–10 % frequency ) and “ rare ” ( 0.01–0.1 % ) effectively conveys the level of risk of side effects to people taking a medicine . Design : R and omised controlled study with unconcealed allocation . Participants : 120 adults taking simvastatin or atorvastatin after cardiac surgery or myocardial infa rct ion . Setting : Cardiac rehabilitation clinics at two hospitals in Leeds , UK . Intervention : A written statement about one of the side effects of the medicine ( either constipation or pancreatitis ) . Within each side effect condition half the patients were given the information in verbal form and half in numerical form ( for constipation , “ common ” or 2.5 % ; for pancreatitis , “ rare ” or 0.04 % ) . Main outcome measure : The estimated likelihood of the side effect occurring . Other outcome measures related to the perceived severity of the side effect , its risk to health , and its effect on decisions about whether to take the medicine . Results : The mean likelihood estimate given for the constipation side effect was 34.2 % in the verbal group and 8.1 % in the numerical group ; for pancreatitis it was 18 % in the verbal group and 2.1 % in the numerical group . The verbal descriptors were associated with more negative perceptions of the medicine than their equivalent numerical descriptors . Conclusions : Patients want and need underst and able information about medicines and their risks and benefits . This is essential if they are to become partners in medicine taking . The use of verbal descriptors to improve the level of information about side effect risk leads to overestimation of the level of harm and may lead patients to make inappropriate decisions about whether or not they take the medicine Abstract Objective : To assess whether provision of educational leaflets or questions on contraception improves knowledge of contraception in women taking the combined contraceptive pill . Design : R and omisation of women into three groups according to type of educational leaflet on contraceptive information . These groups were subdivided into two on the basis of questions on contraception asked by the doctor or practice nurse . The women were followed up by postal question naire 3 months later . Setting : 15 general practice s in South and West region . Subjects : 636 women attending check up appointment for repeat prescription of the combined contraceptive pill . Main outcome measures : Knowledge of : factors causing pill failure , subsequent action , emergency contraception , and all the rules ( pill rules ) that apply to the contraceptive pill . Results : 523 women returned completed question naires ( response rate 82 % ) . Knowledge of contraception with no intervention was low with only 10 ( 12 % ) women knowing all the pill rules . Educational intervention had a highly significant effect on knowledge of : factors causing pill failure ( likelihood ratio χ2=22 ) ; subsequent action ( 21 ) ; emergency contraception ( 24 ) ; and all the pill rules ( 22 ) ( P<0.01 in all cases ) . Improvement in knowledge of all the pill rules occurred with provision of the summary leaflet ( 28 % knew all the rules , adjusted odds ratio 4.04 , 95 % confidence interval 1.68 to 9.75 ) , the Family Planning Association 's leaflet ( 27 % , 3.43 , 1.45 to 8.09 ) , and asking questions ( 26 % , 3.03 , 1.30 to 7.00 ) . Asking questions in addition to provision of leaflets improved knowledge of contraception further for the summary leaflet ( 39 % , 6.81 , 2.85 to 16.27 ) but not for the Family Planning Association leaflet ( 21 % , 2.58 , 1.07 to 6.18 ) . Conclusion : Women attending check ups for repeat prescriptions of the contraceptive pill should be provided with educational leaflets on contraception or asked relevant questions to help improve their knowledge of contraception . Asking questions in addition to providing a summary leaflet is time consuming , but results in the most knowledge gained . Key messages It is very important to most women who take the contraceptive pill to avoid pregnancy Poor knowledge of contraception is common in women taking the contraceptive pill and associated with unwanted pregnancy No r and omised trials have been conducted of educational interventions to improve knowledge of contraception Providing leaflets or asking questions both improve knowledge of contraception The largest effect on knowledge of contraception is from asking questions and providing a summary This paper reports the findings of a study of information given to rheumatology patients using non-steroidal anti-inflammatory drugs . One hundred and twenty patients were r and omized to three groups . Group A received an information leaflet , Group B received both a leaflet and a verbal explanation and Group C received only a verbal explanation . Information was gathered on demography , knowledge base , sources of information , satisfaction with the leaflet and further information requirements . Data were collected by question naires which were completed before r and omization and 8 - 12 weeks later . Analysis indicates the potential benefits of giving information to patients although the full implication s of these benefits are not clear and further research is indicated in this important area OBJECTIVES To develop three tools for assessing the quality of written information provided with new prescriptions in community pharmacies and to identify pharmacy , pharmacist , and patient characteristics associated with the dissemination and quality of that information . DESIGN Observational study . Regression techniques were used to analyze the influence of pharmacy , pharmacist , and shopper ( acting as patient ) characteristics on outcome measures . PARTICIPANTS Trained shoppers ( acting as patients ) visited 306 r and omly selected pharmacies in 8 states . Each shopper presented three prescriptions , answered questions according to a st and ard scenario , accepted the information offered , and paid for the prescriptions . MAIN OUTCOME MEASURES Percentage of shoppers receiving any written information ; quality of written information as judged by an expert panel using explicit criteria . RESULTS Shoppers received an information leaflet with 87 % of the 918 prescriptions dispensed . Although most leaflets provided unbiased information , leaflet length and quality of information varied greatly . A majority of leaflets did not include adequate information about contraindications , pre caution s , and how to avoid harm . Shoppers were more likely to receive leaflets in chain pharmacies and pharmacies with more staff . Information quality also was higher in chain pharmacies . Shopper and pharmacist demographic characteristics were unrelated to the level or quality of written information after controlling for other factors . CONCLUSION The provision of patient leaflets is becoming a routine practice in the states studied . However , most leaflets do not meet quality criteria . It is important for pharmacists to become familiar with criteria for evaluating these leaflets and to take necessary action to improve their quality OBJECTIVES The authors determined patients ' report of prescription drug counseling activities after withdrawal of the pilot program to require patient package inserts in 1980 and implementation of Omnibus Budget Reconciliation Act of 1990 counseling requirements in 1993 . METHODS Four cross-sectional national telephone surveys were conducted in the fall of 1982 , 1984 , 1992 , and 1994 . Telephone households were chosen by r and om-digit dialing . Subjects had obtained a new prescription for themselves or for a family member at a retail pharmacy during the previous 4 weeks . Verbal counseling rates at physician offices and pharmacies for five information categories and the distribution of written information at those locations were determined . RESULTS Spontaneous verbal counseling at the physician 's office has increased slightly , with the largest increases focused on the delivery of side effect and pre caution ary information . Slightly larger increases in pharmacy-delivered information regarding directions for use and pre caution s have occurred . Patient question ing has remained at single digit levels at both sites . The percentage of patients receiving any written information has increased from 5 % to 15 % at the physician 's office and from 16 % to 59 % at the pharmacy . CONCLUSIONS The data indicate small increases in verbal counseling but larger increases in the delivery of written information provided at the pharmacy . In light of Healthy People : 2000 goals for patient counseling and legislation encouraging private-sector initiatives , these data should help to refocus attention on the continuing need for effective patient education interventions OBJECTIVE : To investigate whether patients are influenced by the order in which they learn the risks and benefits of a treatment and whether this effect is attenuated by a treatment ’s associated risk and /or benefit . DESIGN : Subjects were r and omized to review 1 of 6 medical treatment information brochures . SETTING : Waiting rooms of primary care physicians at an academic health center . PARTICIPANTS : Six hundred eighty-five subjects , ages 18 to 70 years . INTERVENTION : Subjects review ed 1 of 3 treatments for symptomatic carotid artery disease . The first ( aspirin ) was low-risk/low-benefit , the second ( carotid endarterectomy surgery ) was high-risk/high-benefit , and the third ( extracranial-to-intracranial bypass surgery ) was high-risk but of unknown benefit . Patients were also r and omized to receive information about risk either before or after benefit . Patients were asked to rate the favorability of the treatment on a scale of 0 to 100 and whether they would consent . Finally , subjects rated how their decisions were influenced by the risk and benefit information . MAIN RESULTS : Subjects evaluating aspirin therapy were influenced by the order of the risk/benefit information . Those learning about risks after benefits had a greater drop in their favorability ratings than subjects learning about risks before benefits ( −10.9 vs −5.2 on a 100-point scale ; P=.02 ) and were less likely to consent ( odds ratio , 2.27 ; P=.04 ) . In contrast , subjects evaluating carotid endarterectomy and extracranial-to-intracranial bypass were not influenced by information order . When subjects were influenced by the order of information , they also reported that the treatment ’s risk had less influence on their decision making ( P<.01 ) . CONCLUSIONS : When patients evaluate low-risk medical interventions , they may form less favorable impressions of the treatment and be less likely to consent to the treatment when they learn about the risks after the benefits . Order effects were not observed with high-risk treatments regardless of potential benefits Insulin/sulphonylurea-treated diabetics attending a busy university diabetic clinic were studied to determine whether issuing drug information sheets and /or age influenced underst and ing and behaviour regarding their disease and its treatment , especially with respect to avoiding hypoglycaemia . Patients were each asked 10 basic questions ( each correct answer scoring 1 ) , stratified by age ( 20 were less than or equal to 45 years and 91 greater than 45 years ) . According to a single-blind r and omised protocol , they were issued or not issued with drug information sheets ( providing information to correctly answer all 10 questions ) . After 2 - 3 months , 107 ( 88 aged greater than 45 years ) were retested and asked whether they recalled an information sheet , read it themselves or had it read to them . Whether or not patients received sheets , corresponding mean aggregate scores were very similar in both age groups and there was no correlation with age . Second test scores yielded clinical ly and statistically significant increments in both the sheet and no sheet groups , respective mean aggregate scores increasing from 4.48 to 5.80 and 5.14 to 6.27 ( P less than 0.001 ) . Among patients issued with sheets , 32 who recalled reading them achieved the greatest improvement in mean scores ( 4.53 to 6.16 , P less than 0.001 ) . Active interaction/communication ( participation in first test , recall and reading of information sheet ) had a favourable educational impact irrespective of age , but merely issuing drug information sheets had no benefit 1 . Cardiologists and pharmacists at the University Hospital of Wales collaborated to write 20 individual leaflets incorporating guidelines for a range of drugs used in the treatment of cardiology patients . The Plain English Campaign advised on the intelligibility and presentation of the information . 2 . One hundred and twenty-five patients from the Regional Cardiology Unit , University Hospital of Wales were r and omly allocated to receive usual verbal counselling about their drug treatment with or without an individualised drug information wallet . Two weeks after discharge from hospital patients completed a postal question naire to determine their satisfaction with the information about their drug treatment and their underst and ing of it . Forty-nine question naires were returned from the leaflet group and 52 from the control group . 3 . The provision of written guidelines result ed in significant improvements in patients ' satisfaction with their drug treatment ( chi 2 = 33.3 , P less than 0.001 ) and their underst and ing of it ( P less than 0.001 , Mann-Whitney test ) . Overall , patients who received leaflets were more likely to be aware of the potential side effects of their drugs but less likely to be apprehensive about them . Succinct guidelines concerning drug therapy can be assimilated by cardiology patients and provide them with a permanent record for future reference 1 . Prescription information leaflets ( PILs ) giving information about non-steroidal anti-inflammatory drugs ( NSAIDs ) , beta-adrenoceptor antagonists and inhaled bronchodilators were evaluated in three small Hampshire towns , while a fourth , in which no leaf Output:	REVIEW METHODS Data from selected studies were tabulated and the results were qualitatively synthesis ed along with findings from the information design and stakeholder workshop str and s. RESULTS Most people do not value the written information they receive . They had concerns about the use of complex language and poor visual presentation and in most cases the research showed that the information did not increase knowledge . The research showed that patients valued written information that was tailored to their individual circumstances and illness , and that contained a balance of harm and benefit information . Most patients wanted to know about any adverse effects that could arise . Patients did not want written information to be a substitute for spoken information from their prescriber . While not everyone wanted written information , those who did wanted sufficient detail to meet their need . Some health professionals thought that written information for patients should be brief and simple , with concerns about providing side-effect information . They saw increasing compliance as a prime function , in contrast to patients who saw an informed decision not to take a medicine as an acceptable outcome . There is a gap between currently provided leaflets and information which patients would value and find more useful .
MS21244	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Stress radiography presents the golden st and ard to quantify posterior laxity in posterior cruciate ligament ( PCL ) insufficiency . Several different techniques are currently available , but comparative data are insufficient . Different stress radiographic techniques result in different values for posterior laxity . Comparative controlled clinical study was design ed . Prior to PCL reconstruction 30 patients underwent a series of stress radiographs : Telos device , hamstring contraction , kneeling view , gravity view , and an axial view . Posterior displacement , side-to-side difference ( SSD ) , condyle rotation , required time , and pain were measured . Posterior displacement was : Telos 12.7 ± 3 mm ( SSD 10.6 ± 3.1 mm ) , hamstring contraction 11.2 ± 3.2 mm ( SSD 8.5 ± 3.4 mm ) , kneeling 14.4 ± 3.8 mm ( SSD 10.2 ± 3.5 mm ) , gravity view 10.5 ± 2.8 mm ( SSD 9.1 ± 2.4 mm ) , and axial view 19.4 ± 6.9 mm ( SSD 8.5 ± 4.1 mm ) . In comparison to Telos the hamstring contraction , gravity , and the axial view underestimated the SSD by approximately 2 mm . Telos and kneeling caused significantly more pain than all other techniques ( P < 0.001 ) . The axial view was fastest ( 115 s , P < 0.001 ) and Telos longest ( 305 s , P < 0.001 ) , respectively . Telos indicated the lowest rotational error with a significant difference between kneeling and gravity ( P < 0.003 ) . In contrast to Telos as the golden st and ard , hamstring contraction , gravity , and axial view underestimated the SSD . Kneeling and Telos are comparable with respect to SSD and pain . Although kneeling indicates a greater rotational error than Telos , it seems to be a reliable alternative for quantifying posterior tibial displacement in a more simple and fast way INTRODUCTION In patients with anterior cruciate ligament ( ACL ) tears , anterior laxity can be measured using stress radiographs or more recently introduced electronic measurement devices . HYPOTHESIS The GNRB ( ® ) arthrometer offers a radiation-free method of measuring anterior knee laxity whose diagnostic value is identical to that of Telos ( ® ) or Lerat stress radiographs . PATIENTS AND METHODS One hundred and fifty-seven patients ( 40 years [ 18 - 69 ] ) scheduled for knee arthroscopy were evaluated using the GNRB ( ® ) and two series of stress radiographs of both knees , one obtained using a 250-N Telos ( ® ) device and the other using the technique described by Lerat ( posterior translation of the femur/tibia under a 9-kg loading device ) . Arthroscopic evaluation of the ACL served as the reference st and ard for assessing the diagnostic performance of the radiological and instrumental laxity measurements . RESULTS Under arthroscopic examination , the ACL was normal in 50.3 % ; " healed to roof of the notch " ( partial tear ) in 9.6 % , " posterolateral bundle preserved " ( partial tear ) in 7.0 % , " healed to the posterior cruciate ligament " ( PCL ) in 17.8 % , and " empty notch " ( complete tear ) in 15.3 % . In partial ACL tears , no significant differences in anterior laxity were found across the three measurement techniques . Telos ( ® ) and GNRB ( ® ) laxities were greater in the complete-tear group than in the normal-ACL , partial-tear , and healed-to-PCL groups . With the Lerat technique , the only significant differences were between the complete-tear group and the normal-ACL and partial-tear groups . Telos ( ® ) and GNRB ( ® ) showed similar diagnostic performance ( sensitivity>62 % , specificity>75 % ) , whereas the Lerat technique lacked sensitivity ( sensitivity=43.2 % , specificity=82.7 % ) at 3 mm . DISCUSSION Diagnostic performance was lower in our study than in earlier reports . The GNRB ( ® ) performed as well as Telos ( ® ) . The non-irradiating nature of GNRB ( ® ) assessment s allows repeated measurements for therapeutic or diagnostic purpose s. LEVEL OF EVIDENCE Level III , prospect i ve case-control study Summary A prospect i ve study was carried out to test the sensitivity and specificity of stress radiography in detecting anterior cruciate ligament deficiency in both knees of 116 patients using the Telos device . In 47 of these a total or partial rupture of the anterior cruciate ligament was diagnosed by arthroscopy , while the ligament was intact in the remaining 69 patients . The mean difference in radiological translation between the injured and the normal knee was greater than 5 mm ( p<0.001 ) in those with anterior cruciate deficiency , and less than 3 mm in the others . A differential displacement of up to 3 mm was considered normal . The sensitivity of the method was less than 67 % and the specificity was 100 % . Clinical diagnosis had a sensitivity of 70.2 % and a specificity of 98.5 % . Our findings suggest that , although a differential translation of more than 3 mm can be diagnostic , smaller differences do not rule out anterior cruciate deficiency . RésuméLes auteurs ont réalisé une étude prospect i ve pour évaluer la sensibilité et la spécificité des radiographies en position forcée dans le diagnostic des insuffisances du ligament croisé antérieur ( LCA ) . Une radiographie en tiroir forcé des deux genoux a d'abord été faite , en utilisant l'appareil Telos , chez 116 patients devant subir une arthroscopie unilatérale . Chez 47 de ces patients une rupture totale ou partielle du LCA a été confirmée par arthroscopie , qui a montrée un ligament intact chez les 69 autres . La différence moyenne de translation entre le genou blessé et le genou sain a été supérieure à 5 mm ( p<0.001 ) chez les patients ayant une insuffisance du LCA et inférieure à 3 mm chez les autres ( une différence de 3 mm a été considérée comme normale ) . La sensibilité de la méthode a été de moins de 67 % et le spécificité de 100 % . L'examen clinique a une sensibilité de 70.2 % et une spécificité de 98.5 % . Ces résultats permettent de penser que , bien qu'une translation supérieure à 3 mm puisse avoir une valeur diagnostique , une moindre différence n'exclut pas une insuffisance du ligament croisé antérieur In a prospect i ve , consecutive , clinical and stress radiographical study , comprising 153 traumatic knee injuries , the value of stress radiographical measurements , gonylaxometry , was studied . Clinical evaluation , gonylaxometry and preoperative evaluation under general anaesthesia were carried out in that order . Then the operative findings were recorded as drawings on st and ard diagrams . These were used as a basis for evaluation of the preoperative tests . Of all the methods evaluated , gonylaxometry was found to provide the most accurate information regarding the knee injury . Very close to this result were the findings under general anaesthesia . Anterior drawer sign was measured gonylaxometrically when damage to the anterior cruciate ligament was present ; posterior drawer meant damage to the posterior cruciate ligament . Partial ruptures of cruciate ligaments did not allow antero-posterior displacements exceeding the critical levels of the test . Small positive medial instability was found with ruptures of profound medial structures , higher values with total rupture of the long superficial collateral b and , and still higher values when cruciate ligament ruptures were also present . The predictive values of a positive radiographical test were 100 per cent as regards medial instability and 98 per cent for drawer looseness . The predictive values of a negative test were 96 per cent for drawer and 92 per cent for medial instability . These figures are based on the total material . 95 per cent confidence limits are given INTRODUCTION The clinical diagnosis of the anterior cruciate ligament ( ACL ) tear is based on demonstrating anterior subluxation of the tibia on the femur . In any of the following perspectives , diagnostic ( cutoff value confirming rupture ) , prognostic ( treatment efficacy ) , and therapeutic ( laxity influencing the treatment ) , this laxity can be measured on stress X-rays . WORKING HYPOTHESIS The diagnostic value of dynamic radiographs is low for ACL rupture . Passive Telos ( ® ) X-rays have better diagnostic value , better radiologic quality , and are easier to carry out than active Franklin-type X-rays . MATERIAL AND METHODS A cohort of 112 patients ( 28 females , 84 males ; mean age , 33.7 years [ range , 18 - 72 years ] ) with an indication for knee arthroscopy were studied prospect ively . Before undergoing the arthroscopic treatment , two series of images of both knees were taken : one series of passive anterior drawer dynamic X-rays on a Telos ( ® ) device at 250 N and a series of active anterior drawer dynamic X-rays according to Franklin ( contraction of the quadriceps against 7 kg of weight at the ankle ) . The arthroscopic evaluation of the ACL ( reference status ) was compared to the anterior laxity measurements ( absolute and differential ) of each knee compartment ( medial , lateral , and average ) to determine the diagnostic value of the two radiological tests . RESULTS We found 70 patients with an " arthroscopically ruptured ACL " , 32 with an " arthroscopically healthy ACL " , and 10 with a " partial rupture " . The measurement of the anterior drawer values on the dynamic X-rays ( active and passive ) by two independent observers was reliable and reproducible ( ICC>0.80 ) , particularly when using the medial compartment ( ICC=0.96 ) and the differential values eliminating the interobserver measurement error and interindividual laxity variations . In terms of X-ray technique , the active images were more frequently painful and the radiographic result showed less good quality than the Telos images . The anterior drawer values in the " healthy ACL " group were significantly less than in the " ruptured ACL " group for the Telos ( ® ) images , whether the measurements were absolute or differential . For the Franklin images , this difference was only significant for the absolute values . Used for diagnosis ( 4-mm differential on the medial compartment ) , the passive dynamic images had lower diagnostic values ( Se=59 % and Sp=90 % ) than the series reported in the literature , which were marked by great heterogeneity . CONCLUSION The measurement of anterior drawer values on Telos ( ® ) and Franklin dynamic X-rays is a reliable and reproducible measurement , particularly when using the medial compartment and differential measurements . This small series did not demonstrate a diagnostic value for the Franklin images , contrary to the Telos ( ® ) X-rays . Used for diagnostic purpose s , the Telos ( ® ) images had a low sensitivity ; consequently , they should be used preferentially for prognostic or therapeutic purpose s. LEVEL OF EVIDENCE Level III , prospect i ve case-control study PURPOSE The objective of this study was to evaluate the efficacy of different stress radiography techniques in quantifying a posterior cruciate ligament ( PCL ) lesion . TYPE OF STUDY Prospect i ve serial study . METHODS Sixty patients with subacute or chronic PCL injuries , confirmed using magnetic resonance imaging ( MRI ) or arthroscopic evaluation , were enrolled in this study . The patients underwent a KT-2000 ( Medmetric , San Diego , CA ) examination and a series of stress radiographs that included a radiographic posterior drawer test with Telos ( Telos , Weterstadt , Germany ) at 90 degrees and 25 degrees of knee flexion , an active radiograph at 90 degrees of knee flexion , and an axial view radiograph . RESULTS Stress radiography performed with Telos showed an average posterior tibial displacement of 11.54 + /- 4.93 mm and 7.97 + /- 3.16 mm at 90 degrees and 25 degrees , respectively . The active radiographs showed an average posterior tibial displacement of 11.48 + /- 5.14 mm . CONCLUSIONS Stress radiographs were shown to be superior to arthrometric evaluation in quantifying posterior tibial translation . The techniques performed with the knee at 90 degrees of knee flexion allowed for greater posterior tibial displacement and , consequently , an easier quantification of the degree of ligament insufficiency . Stress radiographs performed through hamstring contraction gave the same results as those performed with Telos at 90 degrees of knee flexion Seventy-one consecutive patients with posterolateral knee injuries had clinical stability testing abnormalities documented prospect ively . We compared these find ings with the incidence and patterns of their injuries documented at surgery . An abnormal reverse pivot shift test was associated with injury to the fibular col lateral ligament ( P = 0.01 ) , popliteal components ( P = 0.01 ) , and midthird lateral capsular ligament ( P = 0.02 ) . An abnormal posterolateral external-rotation test at 30 ° of flexion was associated with injury to the fibular collateral ligament ( P = 0.0001 ) and lateral gastrocne mius tendon ( P = 0.01 ) . An abnormal adduction test at 30 ° of flex Output:	The diagnostic accuracy of stress radiography including the sensitivity , specificity , and positive and negative predictive values varied considerably depending on the technique and choice of displacement or gapping threshold . Excellent reliability was reported for the diagnosis of anterior cruciate ligament , posterior cruciate ligament , varus , and valgus knee injuries . Inconsistencies were found across studies regarding the efficacy of stress radiography compared with other diagnostic modalities . Conclusions Based on the multitude of stress techniques reported , varying levels of diagnostic accuracy , and inconsistencies regarding comparative efficacy of stress radiography to other diagnostic modalities , we are not able to make specific recommendations with regard to the best stress radiography technique for the diagnosis of knee ligament injuries .
MS21245	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Abstract Objective . Left ventricular hypertrophy ( LVH ) is highly prevalent in chronic kidney disease ( CKD ) and a risk marker for cardiovascular mortality . It was hypothesized that vitamin D deficiency could play an important role in the pathogenesis of left ventricular hypertrophy and dysfunction in CKD . An open-labelled r and omized study was performed comparing the effect of alfacalcidol versus no treatment in patients with CKD 4 , secondary hyperparathyroidism and LVH . The primary endpoint was regression of LVH . Secondary endpoints were changes in left ventricular function . Material and methods . Twenty-four patients were screened . Of these , 14 had LVH according to the criteria used . Six were r and omized to alfacalcidol and seven to no treatment . The patient follow-up was 6 months . Left ventricular mass and function were measured by echocardiography . Results . Parathyroid hormone decreased by 72 % and –3 % in the alfacalcidol-treated and non-treated groups , respectively ( p < 0.05 ) , while serum Ca2 + increased by 9 % and –1.6 % , respectively ( p < 0.05 ) , and serum phosphate was unchanged . The left ventricular mass index was unchanged , whereas fractional shortening ( 20 % vs 2 % , p < 0.005 ) and Tei index ( 36 % vs 12 % , p < 0.05 ) increased significantly . Systolic and diastolic blood pressure was unchanged . Conclusion . Short-term treatment with alfacalcidol did not induce regression of LVH ; however , left ventricular function became hyperdynamic but less effective in patients with CKD . This could be problematic in the long term CONTEXT Decreased calcitriol production due to impaired renal function may be a significant risk factor for falls in normal aging population . OBJECTIVE The objective of the study was to examine the association between creatinine clearance ( CrCl ) and the incidence of falls and fallers in groups treated with placebo , calcitriol , estrogen therapy (ET)/estrogen + progestin therapy ( HT ) , and calcitriol + ET/HT . DESIGN This was a 3-yr , double-blind , placebo-controlled study design ed to test the efficacy of calcitriol and ET/HT on bone loss and falls with analysis by intention to treat and post hoc . SETTING The study was conducted at an academic outpatient center . PARTICIPANTS Four hundred eighty-nine normal elderly women aged 65 - 77 yr ; 415 women completed the study . INTERVENTION Subjects were r and omized to placebo , calcitriol 0.25 mug twice a day , ET daily ( conjugated equine estrogens 0.625 mg ) , HT ( conjugated equine estrogen 0.625 mg + medroxyprogesterone acetate 2.5 mg ) and calcitriol + ET/HT . MAIN OUTCOME MEASURES Cumulative number of falls and fallers were compared between groups with 24-h urine CrCl less than 60 and 60 ml/min or greater . RESULTS Calcitriol treatment decreased the number of fallers and falls . Low CrCl less than 60 ml/min was a predictor of the number of falls per person but not fallers in the placebo group ( P = 0.007 ) . In the low CrCl group ( < 60 ml/min ) , the rate of falls decreased on calcitriol by 53 % [ 95 % confidence interval ( CI ) -71 % to -22 % ; P = 0.003 ] , calcitriol + ET/HT by 61 % ( 95 % CI -76 % to -37 % ; P = 0.001 ) , and ET/HT by 25 % ( 95 % CI : -55 % to + 24 % ; not significant ) . Calcitriol reduced the rate of falls by 30 % ( 95 % CI -49 % to -4 % ; P = 0.027 ) in the CrCl 60 ml/min or greater group . CONCLUSION Calcitriol treatment decreases falls in all subjects but especially in elderly women with decreased renal function ( < 60 ml/min ) and frequent fallers Thirteen patients in the predialysis phase of chronic renal failure ( CRF ) were treated with calcitriol ( 0.25 micrograms/day ) and 12 with placebo . After 1 year of study , an increase in bone mineral density in the calcitriol group measured by dual-energy X-ray absorptiometry was seen for the femoral neck and lumbar spine when compared to the placebo group ( p < 0.001 and p < 0.01 , respectively ) . We conclude that a steady low dose of calcitriol started in the predialysis phase of CRF is beneficial to the patients with CRF . This may be partly due to suppression of secondary hyperparathyroidism BACKGROUND Higher doses of calcitriol are effective in lowering markedly elevated 1,84 PTH levels of patients with renal secondary hyperparathyroidism . It has not been established , however , whether prophylactic administration of low doses of calcitriol prevents an increase of 1,84 PTH without causing side-effects , i.e. hypercalcaemia , hypercalciuria , or hyperphosphataemia . STUDY DESIGN We carried out a placebo-controlled , double-blind prospect i ve multicentre trial over 12 months in 45 patients with mild to moderate renal failure . Criteria for inclusion were S-creatinine 1.4 mg/dl and 1,84 PTH > 6 pmol/l ( normal 6 ) . Calcitriol 0.125 microgram/day per os was compared with placebo . The patients received calcium carbonate per os if serum P exceeded 1.7 mmol/l . RESULTS Baseline 1,84 iPTH concentrations were not significantly different , i.e. 14.0 pmol/l ( 6.7 - 63.3 ) on placebo vs 16.2 ( 6.85 - 82.0 ) on calcitriol . Intention to treat analysis revealed a significant difference of final 1,84 iPTH , i.e. 27.8 ( 4.2 - 68.5 ) on placebo vs 18.2 ( 4.45 - 75.5 ) on calcitriol . On post-hoc analysis the difference was even more pronounced at S-creatinine concentrations above 3 mg/dl . S-calcium , S-phosphate , and urinary excretion of calcium did not change significantly on either placebo or on calcitriol . There were no episodes of hypercalcaemia or hyperphosphataemia . There was no significant difference of final S-creatinine or change in S-creatinine between placebo and calcitriol . One patient on calcitriol and two on placebo progressed to terminal renal failure . Bone alkaline phosphatase as a non-invasive index of bone metabolism was not decreased to subnormal levels . CONCLUSION The results document that a therapeutic window exists in patients with moderate renal failure and elevated of 1,84 iPTH , where low-dose calcitriol ( 0.125 microgram/day ) prevents the increase in 1,84 iPTH without causing side-effects . This observation suggests that the parathyroid is more sensitive to calcitriol than intestine and bone 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 safety and efficacy of paricalcitol injection have been well established for the prevention and treatment of secondary hyperparathyroidism ( SHPT ) in patients with chronic kidney disease ( CKD ) stage 5 . The capsule form of paricalcitol was developed to provide a convenient dosage form for patients with stages 3 and 4 CKD . METHODS Three r and omized , placebo-controlled , phase-3 trials were conducted in patients with stages 3 and 4 CKD with SHPT . Enrollment criteria included an estimated glomerular filtration rate between 15 and 60 mL/min/1.73 m2 ( 0.25 and 1.00 mL/s/1.73 m2 ) , an average of 2 consecutive intact parathyroid hormone ( iPTH ) levels greater than 150 pg/mL ( ng/L ) , 2 consecutive serum calcium levels between 8.0 and 10.0 mg/dL ( 2.00 and 2.50 mmol/L ) , and 2 consecutive serum phosphorus levels of 5.2 mg/dL or less ( < or = 1.68 mmol/L ) . Two studies used a thrice-weekly dosing regimen and 1 study used a once-daily dosing regimen for 24 weeks . Dosing was based on serum iPTH , calcium , and phosphorus levels . The primary efficacy end point is 2 consecutive decreases in iPTH levels greater than 30 % from baseline . RESULTS Two hundred twenty patients participated ( n = 107 , paricalcitol ; n = 113 , placebo ) . At least 2 consecutive decreases in iPTH levels of 30 % or greater from baseline occurred in 91 % of paricalcitol versus 13 % of placebo patients ( P < 0.001 ) . Incidences of hypercalcemia , hyperphosphatemia , and elevated calcium-phosphorus product levels were not significantly different between groups . Similarly , no significant differences in urinary calcium and phosphorus excretion or deterioration in kidney function were detected in patients administered paricalcitol compared with placebo . CONCLUSION Paricalcitol capsule was well tolerated and effectively decreased iPTH levels with minimal or no impact on calcium levels , phosphorus balance , and kidney function in patients with stages 3 and 4 CKD OBJECTIVE To study the efficacy of synthetic 1,25 dihydroxyvitamin D3 ( calcitriol ) in the treatment of osteoporosis . DESIGN Two-year , double-blind , r and omized clinical trial . SETTING University medical center . PATIENTS Fifty postmenopausal women with vertebral fractures recruited by referral . INTERVENTION Calcium intake was adjusted to 25 mmol/d ( 1000 mg/d ) at baseline . Patients were then r and omized to treatment with either calcitriol or placebo . During the study , calcium intake was reduced to 15 mmol/d ( 600 mg/d ) and the dose of calcitriol was adjusted to maintain serum calcium less than 2.74 mmol/L ( less than 11.0 mg/dL ) or urine calcium less than 9.96 mmol/d ( less than 400 mg/d ) . MEASUREMENTS AND MAIN RESULTS After 2 years , the mean dose of calcitriol in the treated group was 0.62 micrograms/d . Bone mineral density of the spine increased 1.94 % with calcitriol therapy and decreased 3.92 % with placebo ( P = 0.001 ) . Total body calcium increased 0.21 % with calcitriol therapy and decreased 1.85 % with placebo ( P = 0.004 ) . Patients receiving placebo had significant decreases in spine density ( P = 0.0007 ) and total body calcium ( P = 0.0004 ) . There were no differences in vertebral fracture rates between the groups . Renal function studies were not statistically different between the groups after 2 years . CONCLUSION The treatment of postmenopausal osteoporotic women with synthetic calcitriol for 2 years was associated with increases in spine density and total body calcium . No adverse effects on renal function were seen after long-term calcitriol therapy BACKGROUND Bone loss occurs during the first 6 months after renal transplantation ( RT ) , and corticosteroid therapy plays an important role . Although calcium plus vitamin D administration prevents corticosteroid-induced osteoporosis , its use in RT recipients is limited by the risk of hypercalcemia . METHODS This double-blind , r and omized , and controlled prospect i ve intervention trial examined the effect of intermittent calcitriol ( 0.5 microg/48 h ) during the first 3 months after RT , plus oral calcium supplementation ( 0.5 g/day ) during 1 year with calcium supplementation alone . The primary outcome measure was the change in bone mineral density ( BMD ) at 3 and 12 months after RT ; we also explored whether the effect of calcitriol on BMD was different among vitamin D receptor ( VDR ) genotypes ( BsmI ) . Forty-five recipients were r and omized to calcitriol therapy ( CT ) and 41 were r and omized to placebo ( PL ) . RESULTS Both groups had a similar degree of pre-existing hyperparathyroidism ( 197 + /- 229 vs. 191 + /- 183 pg/mL ) , but a more pronounced decrease of parathyroid hormone ( PTH ) levels after RT was observed in CT patients ( at 3 months : 61.4 + /- 42.2 vs. 85.7 + /- 53.1 pg/mL , P= 0.02 ; at 12 months : 67.3 + /- 33.7 Output:	Administration of VDRAs increased serum creatinine levels . Subgroup analysis of studies that did not use SCr-based measures did not indicate a lower GFR in the VDRA group .
MS21246	*TASK* the task is to summarize an input biomedical literature in six sentences *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 substantial number of older hypertensive patients have stage 1 isolated systolic hypertension ( systolic blood pressure between 140 and 159 mm Hg and diastolic blood pressure < 90 mm Hg ) , but there are currently no data showing that drug treatment is effective , safe , and /or beneficial . To compare the effects of active treatment compared with placebo on blood pressure , left ventricular hypertrophy , and quality of life among older stage 1 isolated systolic hypertensive patients , a r and omized , double-blind , parallel-group , multicenter clinical trial comparing felodipine ( 2.5 , 5 , or 10 mg once daily ) and matching placebo was performed in 171 patients ( 49 % male , average age 66±7 years , with 49 % white and 30 % Hispanic ) with a baseline blood pressure of 149±7/83±6 mm Hg . During 52 weeks of treatment , patients r and omized to active treatment achieved significantly lower blood pressures ( 137.0±11.7/80.2±7.6 mm Hg for extended-release felodipine versus 147.5±16.0/83.5±9.7 mm Hg for placebo , P < 0.01 for each ) , a reduced incidence of left ventricular hypertrophy ( 7 % for extended release felodipine versus 24 % for placebo , P < 0.04 ) , and improved quality of life ( change in Psychological General Well-Being index , 3.0±6.8 for extended-release felodipine versus −0.8±10.3 for placebo , P < 0.01 ) versus baseline . There were no clinical ly significant differences between treatments in tolerability or adverse effects . Stage 1 isolated systolic hypertension can be effectively and safely treated pharmacologically . Treatment reduced progression to the higher stages of hypertension , reduced the incidence of left ventricular hypertrophy , and improved an overall measure of the quality of life . Larger and longer studies will be needed to document any long-term reduction in cardiovascular event rates associated with treating stage 1 systolic hypertension Although the benefits of antihypertensive treatment in " young " elderly ( under 70 years ) hypertensive patients are well established , the value of treatment in older patients ( 70 - 84 years ) is less clear . The Swedish Trial in Old Patients with Hypertension ( STOP-Hypertension ) was a prospect i ve , r and omised , double-blind , intervention study set up to compare the effects of active antihypertensive therapy ( three beta-blockers and one diuretic ) and placebo on the frequency of fatal and non-fatal stroke and myocardial infa rct ion and other cardiovascular death in hypertensive Swedish men and women aged 70 - 84 years . We recruited 1627 patients at 116 health centres throughout Sweden , who were willing to participate , and who met the entry criteria of three separate recordings during a 1-month placebo run-in period of systolic blood pressure between 180 and 230 mm Hg with a diastolic pressure of at least 90 mm Hg , or a diastolic pressure between 105 and 120 mm Hg irrespective of the systolic pressure . The total duration of the study was 65 months and the average time in the study was 25 months . 812 patients were r and omly allocated active treatment and 815 placebo . The mean difference in supine blood pressure between the active treatment and placebo groups at the last follow-up before an endpoint , death , or study termination was 19.5/8.1 mm Hg . Compared with placebo , active treatment significantly reduced the number of primary endpoints ( 94 vs 58 ; p = 0.0031 ) and stroke morbidity and mortality ( 53 vs 29 ; p = 0.0081 ) . Although we did not set out to study an effect on total mortality , we also noted a significantly reduced number of deaths in the active treatment group ( 63 vs 36 ; p = 0.0079 ) . The benefits of treatment were discernible up to age 84 years . We conclude that antihypertensive treatment in hypertensive men and women aged 70 - 84 confers highly significant and clinical ly relevant reductions in cardiovascular morbidity and mortality as well as in total mortality BACKGROUND Stevioside , a natural glycoside isolated from the plant Stevia rebaudiana Bertoni , has been used as a commercial sweetening agent in Japan and Brazil for > 20 years . Previous animal and human studies have indicated that stevioside has an antihypertensive effect . OBJECTIVES This study was undertaken to investigate the long-term ( 2-year ) efficacy and tolerability of stevioside in patients with mild essential hypertension . Secondary objectives were to determine the effects of stevioside on left ventricular mass index ( LVMI ) and quality of life ( QOL ) . METHODS This was a multicenter , r and omized , double-blind , placebo-controlled trial in Chinese men and women aged between 20 and 75 years with mild essential hypertension ( systolic blood pressure [ SBP ] 140 - 159 mm Hg and diastolic blood pressure [ DBP ] 90 - 99 mm Hg ) . Patients took capsules containing 500 mg stevioside powder or placebo 3 times daily for 2 years . Blood pressure was measured at monthly clinic visits ; patients were also encouraged to monitor blood pressure at home using an automated device . LVMI was determined by 2-dimensional echocardiography at baseline and after 1 and 2 years of treatment . QOL was assessed using the Medical Outcomes Study 36-Item Short-Form Health Survey . Electrocardiographic , laboratory , and QOL parameters were assessed at the beginning of treatment , and at 6 months , 1 year , and 2 years . RESULTS One hundred seventy-four patients ( 87 men , 87 women ) were enrolled in the study , and 168 completed it : 82 ( 42 men , 40 women ; mean [ SD ] age , 52 [ 7 ] years ) in the stevioside group and 86 ( 44 women , 42 men ; mean age , 53 [ 7 ] years ) in the placebo group . After 2 years , the stevioside group had significant decreases in mean ( SD ) SBP and DBP compared with baseline ( SBP , from 150 [ 7.3 ] to 140 [ 6.8 ] mm Hg ; DBP , from 95 [ 4.2 ] to 89 [ 3.2 ] mm Hg ; P < 0.05 ) and compared with placebo ( P < 0.05 ) . Based on patients ' records of self-monitored blood pressure , these effects were noted beginning approximately 1 week after the start of treatment and persisted throughout the study . There were no significant changes in body mass index or blood biochemistry , and the results of laboratory tests were similar in the 2 groups throughout the study . No significant difference in the incidence of adverse effects was noted between groups , and QOL scores were significantly improved overall with stevioside compared with placebo ( P < 0.001 ) . Neither group had a significant change in mean LVMI . However , after 2 years , 6 of 52 patients ( 11.5 % ) in the stevioside group had left ventricular hypertrophy ( LVH ) , compared with 17 of 50 patients ( 34.0 % ) in the placebo group ( P < 0.001 ) . Of those who did not have LVH at baseline , 3 of 46 patients ( 6.5 % ) in the stevioside group had developed LVH after 2 years , compared with 9 of 37 patients ( 24.3 % ) in the placebo group ( P < 0.001 ) . CONCLUSIONS In this 2-year study in Chinese patients with mild hypertension , oral stevioside significantly decreased SBP and DBP compared with placebo . QOL was improved , and no significant adverse effects were noted Summary The Syst-Eur Trial is a concerted action of the European Community ’s Medical and Health Research Programme . The trial is carried out in consultation with the World Health Organization , the International Society of Hypertension , the European Society of Hypertension and the World Hypertension League . This article describes the objectives and the protocol of Syst-Eur , a multicentre trial design ed by the European Working Party on High Blood . Pressure in the Elderly ( EWPHE ) , to test the hypothesis that antihypertensive treatment of elderly patients with isolated systolic hypertension results in a significant change in stroke morbidity and mortality . Secondary endpoints include cardiovascular events , such as myocardial infa rct ion and congestive heart failure . To be eligible patients must be at least 60 years old and have a systolic blood pressure averaging 160–219 mmHg with a diastolic pressure less than 95 mmHg . Patients must give their informed consent and be free of major cardiovascular and non-cardiovascular diseases at entry . The patients are r and omized to active treatment or placebo . Active treatment consists of nitrendipine ( 10–40 mg/day ) , combined with enalapril ( 5–20 mg/day ) and hydrochlorothiazide ( 12.5–25 mg/day ) , as necessary . The patients of the control group receive matching placebos . The drugs ( or matching placebos ) are stepwise titrated and combined in order to reduce systolic blood pressure by 20 mmHg at least to a level below 150 mmHg . Morbidity and mortality are monitored to enable an intention-to-treat and per protocol comparison of the outcome in the 2 treatment groups . A one-year pilot trial ( 1989 ) showed that the protocol is practicable . The Ethics Committee therefore decided to start the definite study ( 1990 ) , in which r and omized patients will be followed for 5 years . Recruitment of new centres and of the required 3,000 patients will last 3 years ( until 1993 ) Objective To compare quality of life in elderly patients with isolated systolic hypertension allocated r and omly to groups to receive placebo or active treatment in the Systolic Hypertension in the Elderly Trial . Design Double-blind r and omized controlled trial . Methods Patients aged 60 years were allocated r and omly to groups to receive first-line treatment with nitrendipine ( with second- and third-line enalapril and hydrochlorothiazide ) or placebo . Trained interviewers administered trail-making tests ( Trail A and B ) , Brief Assessment Index ( a measure of depressed mood ) and four subscales from the Sickness Impact Profile ( Ambulation , Social Interaction , Sleep and Rest , and Home work ) . Results Six hundred and ten patients completed a baseline and at least one follow-up question naire . Trail-making scores were slower in actively treated patients , especially in the first 6 months of follow-up when the between-group effect sizes were 0.25 [ 95 % confidence interval ( CI ) 0.07 to 0.43 ] for Trail-making A and 0.13 ( 95 % CI −0.05 to 0.31 ) for Trail-making B. Across the 4 years of follow-up , patients receiving active treatment were more likely to report problems on the Social Interaction scale than were placebo-treated patients ( odds ratio 1.32 , 95 % CI 1.02 to 1.69 ) , equivalent to a 7 % difference . There were no significant differences between active and placebo treatment in the other Sickness Impact Profile dimensions or in the measure of depression . Conclusions Active treatment in the Systolic Hypertension in Europe trial was associated with some small adverse impacts on quality of life BACKGROUND Results of previous studies of white older adults suggest that antihypertensive medications preserve cognition . We assessed the long-term effect of antihypertensive medications on cognitive function in a community sample of African American older adults . METHODS We conducted longitudinal surveys and clinical assessment of cognitive function in a r and om sample of 2212 community-dwelling African Americans 65 years and older . We identified 1900 participants without evidence of cognitive impairment at baseline , 1617 of whom had subsequent follow-up information , and 946 of whom had blood pressure measurements . Cognitive function was measured at baseline and at 2 and 5 years by means of scores on the Community Screening Instrument for Dementia and neuropsychological and clinical assessment for dementia and cognitive impairment . Prescription and nonprescription medication use was derived from in-home inspection of medications and participant and informant reports . RESULTS Of 1900 participants , 288 ( 15.2 % ) developed incident cognitive impairment . Using logistic regression to control for the effects of age , sex , education , baseline cognitive scores , and hypertension and angina or myocardial infa rct ion , we found that antihypertensive medications reduced the odds of incident cognitive impairment by 38 % ( odds ratio , 0.62 ; 95 % confidence interval , 0.45 - 0.84 ) . Corresponding analysis using blood pressure measurements on the subset of participants was inconclusive . CONCLUSION Antihypertensive medication use is associated with preservation of cognitive function in older African American adults The Study on COgnition and Prognosis in the Elderly ( SCOPE ) was a multinational , r and omised , double-blind study to assess the effects of c and esartan 8–16 mg daily on cardiovascular events and cognitive function in elderly patients ( aged 70–89 years ) with mild to moderate hypertension . A total of 4937 patients were r and omised to c and esartan or placebo with other antihypertensive drugs Output:	There was no convincing evidence from the trials identified that blood pressure lowering prevents the development of dementia or cognitive impairment in hypertensive patients with no apparent prior cerebrovascular disease .
MS21247	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Importance It is important that clinicians underst and consequences of thyoridectomy on swallowing from the patient perspective to better care for this population . Objective Using rigorous qualitative methodology , this study set out to characterize the effect of swallowing-related symptoms after thyroidectomy on patient quality of life and swallowing-related outcomes . Design , Setting , and Participants Prospect i ve , grounded theory analysis of interviews with 26 patients at 3 time points after thyroidectomy ( 2 weeks , 6 weeks , and 6 months ) . Data were collected from an ongoing clinical trial ( NCT02138214 ) , and outpatient interviews were conducted at the University of Wisconsin Hospital and Clinics . All participants were age 21 to 73 years with a diagnosis of papillary thyroid cancer without cervical or distant metastases and had undergone total thyroidectomy . Exclusion criteria were preexisting vocal fold abnormalities ( eg , polyps , nodules ) , neurological conditions affecting the voice or swallowing ability , and /or development of new-onset vocal fold paresis or paralysis ( lasting longer than 6 months ) after total thyroidectomy . Interventions Total thyroidectomy . Main Outcomes and Measures Symptoms of dysphagia and related effects on quality of life elicited through grounded theory analysis of semistructured interviews with patients after thyroidectomy design ed to foster an open-ended , patient-driven discussion . Results Of the 26 patients included , 69 % were women ( n = 18 ) ; mean ( SD ) age , 46.4 ( 14.1 ) years ; mean ( SD ) tumor diameter 2.2 ( 1.4 ) cm . Two weeks after thyroidectomy , 80 % of participants ( n = 20 ) reported at least 1 swallowing-related symptom when prompted by the interview cards ; during the open interview , 53 % of participants ( n = 14 ) volunteered discussion of swallowing-related symptoms unprompted . However , only 8 % of participants in this study ( n = 2 ) qualified for a follow-up dysphagia evaluation , indicating that the majority of reported symptoms were subjective in nature . Six weeks and 6 months after thyroidectomy , 42 % ( n = 11 ) and 17 % ( n = 4 ) of participants , respectively , reported continued swallowing symptoms using the prompts ; 12 % ( n = 3 ) discussed symptoms without prompting cards at both time points . Conclusions and Relevance Swallowing symptoms after thyroidectomy are underreported in the literature . This study revealed that as many as 80 % of patients who have thyroidectomy may experience swallowing-related symptoms after surgery , and many develop compensatory strategies to manage or reduce the burden of these symptoms . Considering the large number of individuals who may experience subjective dysphagia , preoperative counseling should include education and management of such symptoms HYPOTHESES Goiter is a surgically reversible cause of positional dyspnea ( PD ) . Substernal tracheal compression ( TC ) predicts PD relief after thyroidectomy ( Tx ) . DESIGN Retrospective analysis of a prospect i ve structured management algorithm . SETTING Endocrine surgery academic center . METHODS Before Tx , 1081 patients were queried about PD . Those patients with substernal goiter underwent computed tomography , and their degree of TC was estimated as greatest percent reduction of transverse tracheal diameter . For 197 patients with PD , TC , or both , surgical outcomes were examined with a mean follow- up of 12.6 months . After Tx , patients who carried the diagnosis of obstructive sleep apnea were referred for repeat sleep study evaluation . RESULTS Positional dyspnea was reported by 188 of 1081 patients , and after Tx the PD improved or resolved in 82.4 % . In the 151 patients with substernal goiter , TC was present on imaging in 97.2 % ; the mean ( range ) TC was 34 % ( 5%-90 % ) . Patients with TC had a high likelihood of PD ( 93.5 % ) . After substernal goiter resection , PD improved in stepwise association with total resected thyroid gl and weight . Improvement in PD was strongly predicted by both gl and weight of 100 g or more ( P.001 ) and by TC of 35 % or more ( P.01 ) . After Tx , 59 of 77 snorers ( 76.6 % ) reported improvement in snoring , 77.1 % of patients with obstructive sleep apnea reported improved PD , and 2 of 3 retested patients with obstructive sleep apnea demonstrated objective improvement in sleep study apnea-hypopnea index . CONCLUSIONS Resection of bulky goiter frequently improves PD , which in substernal goiter is highly associated with TC . Either PD or TC of 35 % or more prompt Tx . Goiter should be considered when obstructive sleep apnea is diagnosed Background Voice and swallowing alterations are common complaints after thyroidectomy , even in the absence of laryngeal nerve impairment . However , voice and swallowing functions after robotic thyroidectomy have not been thoroughly investigated . This study compared the functional outcomes for voice and swallowing after robotic thyroidectomy and conventional open thyroidectomy . Methods The study prospect ively analyzed the voice and swallowing functions of patients with thyroid nodules who underwent robotic thyroidectomy by a gasless unilateral axillo-breast ( GUAB ) approach ( 50 cases ) or by conventional open thyroidectomy ( 61 cases ) from September 2009 to October 2010 . Videolaryngostroboscopy or flexible laryngoscopy was performed pre- and postoperatively . Subjective voice and swallowing alterations were assessed by question naire preoperatively and then 1 day , 1 week , 1 month , 3 months , and 6 months postoperatively . In addition , objective acoustic voice analysis was performed using a Multidimensional Voice Program , with Voice Range Profiles and maximum phonation times measured preoperatively and then 1 week , 1 month , 3 months , and 6 months postoperatively . Results Subjective postoperative voice function was significantly better in the robotic group at 1 day , 1 month , and 3 months postoperatively than in the open group . The mean values of fundamental frequency , jitter , shimmer and noise-to-harmonic ratio before and after surgery did not differ between the two groups . However , the frequency range and the highest frequency were significantly better in the robotic group than in the open group at 3 months postoperatively . Subjective swallowing function did not differ between the two groups . Conclusion Postoperative voice function is better with robotic thyroidectomy using the GUAB approach than with conventional open thyroidectomy . This is an advantage of robotic thyroidectomy by the GUAB approach in addition to the excellent cosmesis ObjectiveS wallowing disorders are frequent complaints after thyroidectomy even in the absence of recurrent laryngeal nerve palsy . The aim of this study was to assess different symptoms in relation to laryngeal mobility following thyroidectomy . Material s and methods 53 patients ( mean age 52.4 ± 12.5 years ; 36 female ) with initially benign diagnosis and intact recurrent nerve functioning were prospect ively evaluated . Laryngeal movement was analyzed by ultrasound preoperatively and 1 , 3 , and 6 months postoperatively . In addition , a dysphagia and voice-specific quality -of-life question naire was used . Results Mean laryngeal movement differed between genders preoperatively and postoperatively result ing in a recovery predominantly in women ( reduction of mobility at 1 , 3 , and 6 months postoperatively in females was 6.0 , 3.7 , and 1.5 mm , and in males 13.8 , 11.7 , and 10.3 mm , respectively ) . Mainly , women reported hoarseness ( 9 females ) and cervical discomfort ( 7 females , 3 males ) 1 month postoperatively . After 6 months , these complaints resolved ( cervical discomfort 1 female ) . Conclusion Laryngeal mobility was significantly impaired postoperatively and only females revealed a recovery close to baseline after 6 months . Although showing only a small grade of recovery of laryngeal movement , subjective clinical symptoms were found to be rare in male patients BACKGROUND We performed a prospect i ve analysis on voice and swallowing alterations following total thyroidectomy ( TT ) , in the absence of recurrent nerve injury . METHODS Patients aged 21 to 65 years undergoing TT , in the absence of laryngeal/pulmonary disease , previous neck surgery , or malignant diseases , were subjected to videostrobolaryngoscopy ( VSL ) , acoustic voice analysis ( AVA ) , and maximum phonation time ( MPT ) tests preoperatively and 3 months postoperatively . Voice impairment scores ( VIS ) and swallowing impairment scores ( SIS ) were obtained preoperatively , and at 1 week , 1 month , and 3 months postoperatively . RESULTS Among the 127 selected patients , 39 completed the postoperative evaluation . No recurrent nerve injury was observed during the postoperative VSL in any of the patients . Preoperative and postoperative AVA and MPT scores did not differ significantly . The mean postoperative VIS was significantly higher than the preoperative VIS at 1 week and 1 month after TT ( 13.7 and 9.6 vs 4.4 , respectively ; P < .05 ) but not 3 months after TT ( 6.7 ) . The mean SIS was higher than the preoperative SIS at 1 week , 1 month , and 3 months after TT ( 10.3 , 6.0 , and 2.8 vs 0.5 , respectively ; P < .05 ) . CONCLUSIONS Physicians should inform patients that transient voice and swallowing symptoms may occur following total thyroidectomy , and our data suggest mild symptoms may occur in the majority of operated patients BACKGROUND Patients undergoing thyroidectomy often complain aerodigestive disorders . In a previous study we showed the associations between voice impairment and proximal acid reflux , swallowing impairment and Upper Esophageal Sphyncter ( UES ) incoordination and the decrease in UES pressure in thirty-six patients observed before and soon afterwards uncomplicated thyroidectomy . This study investigated the state of post-thyroidectomy esophageal motility changes and its associations with these disorders after 18 - 24 months . PATIENTS AND METHODS The thirty-six patients prospect ively recruited according to selection criteria ( thyroid volume ≤60 ml , benign disease , age 18 - 65 years , previous neck surgery , thyroiditis , pre- or postoperative vocal cord palsy ) underwent voice ( VIS ) and swallowing ( SIS ) impairment scores , esophageal manometry and pH monitoring once again . RESULTS After 18 - 24 months , both VIS and SIS recovered ( respectively : p=0,022 ; p=0,0001 ) ; UES pressure increased ( p=0,0001 ) nearing the preoperative values . The persistence of swallowing complaints were associated with the persistence of esophageal incoordination ( p=0,03 ) ; the association between voice impairment and proximal acid reflux was confirmed ( p<0,001 ) . CONCLUSIONS Our study confirms that aerodigestive disorders after uncomplicated thyroidectomy , largely transient , are strictly connected with upper esophageal motility changes . In this viewpoint , the innervation of upper aerodigestive anatomical structures ( larynx , pharynx , upper esophagus ) and its variations should be focused Objective Swallowing and voice impairment are common after thyroidectomy . We evaluated short-term functional changes in esophageal motility in a series of patients who had undergone total thyroidectomy . Several studies have investigated these symptoms by means of interviews or question naires . Study Design Prospect i ve study . Setting Academic research . Material s and Methods Thirty-six consenting patients were prospect ively recruited . Eligibility criteria were thyroid volume ≤60 mL , benign disease , and age between 18 and 65 years . Exclusion criteria were previous neck surgery , severe thyroiditis , hyperthyroidism , and pre- or postoperative vocal cord palsy . Voice impairment score , swallowing impairment score , lower esophageal sphincter pressure , esophageal motility , upper esophageal pressure , and coordination were evaluated preoperatively and 30 to 45 days after surgery . Results Postoperative swallowing impairment ( appearance or worsening of dysphagia ) was found in 20 % of patients and voice impairment in more than 30 % . Both preoperative and postoperative esophageal motility were similar . All patients showed an average decrease of 25 % in upper esophageal pressure , although the pressure was within normal range . Swallowing alterations were associated with upper esophageal incoordination ( P < .03 ) , and proximal acid reflux was significantly associated with voice impairment ( P < .02 ) . Conclusion After uncomplicated thyroidectomy , decreased upper esophageal pressure may explain both pharyngeal ( dysphagia ) and laryngeal ( vocal impairment ) exposure to acid . In the future , proton pump inhibitor therapy protocol s should be evaluated A globus sensation is one of the most common complaints in otolaryngologic clinics , and laryngopharyngeal reflux is the most common cause . However , thyroid nodules also can cause globus symptoms . The purpose of this study was to identify Output:	The prevalence increased with goiter size and with the extent of substernal extension . Esophageal physiology changes : Goiter patients had increased esophageal transit time , positively correlated with goiter size , but unrelated to esophageal motility disturbances . Decrease in the upper esophageal sphincter pressure occurred early after surgery , and normalized within 6 months . Swallowing related patient-reported outcomes : Evaluated by vali date d question naires , swallowing symptoms worsened in the early period after thyroidectomy , but improved after 6 months , as compared to baseline . Conclusions : Thyroidectomy relieved patients with goiter from dysphagia , within 6 months of surgery probably via increase in the cross-sectional area of the esophagus .
MS21248	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Fruquintinib ( HMPL-013 ) is a novel oral small molecule compound that selectively inhibits vascular endothelial growth factor receptors-1 , -2 , and -3 with potent inhibitory effects on multiple human tumor xenografts . This first-in-human study was conducted to assess the maximum tolerated dose and dose-limiting toxicities , safety and tolerability , pharmacokinetics , and preliminary anti-tumor activity of fruquintinib . Methods Patients 18–70 years old with advanced solid tumors refractory to st and ard therapies were recruited . Fruquintinib was administered orally in 4-week repeating cycles in two regimens , either once daily continuously or once daily for 3-week on/1-week off , until discontinuation due to toxicity or tumor progression . Adverse events were assessed using National Cancer Institute Common Terminology Criteria for Adverse Events v4.0.3 . Pharmacokinetic parameters were measured after a single dose and in multiple dosing . Tumor response was assessed by Response Evaluation Criteria in Solid Tumors v1.0 . Results Forty patients were enrolled into 5 cohorts in continuous regimen and 2 cohorts in 3-week-on/1-week-off regimen . The most common grade 3/4 adverse events were h and –foot skin reaction , hypertension , and thrombocytopenia . PK analysis showed good and rapid absorption followed by slow terminal elimination with a mean half-life of approximately 42 h which was consistent across all dose groups . Thirty-four patients were evaluable for tumor response , including 14 with partial response and 14 with stable disease . Conclusions Fruquintinib showed an acceptable safety profile and preliminary evidence of anti-tumor activity in patients with advanced solid tumors . The recommended dose was determined to be either 4 mg QD on a continuous regimen or 5 mg QD on a 3-week-on/1-week-off regimen 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 Abstract Objective To describe the use of regorafenib for the treatment of metastatic colorectal cancer ( mCRC ) in clinical practice in the Czech Republic , and to describe the clinical outcomes of patients in terms of safety and survival . Patients and Methods The data of patients treated with regorafenib were extracted from the national CORECT registry . The CORECT registry is a non-interventional post-marketing data base , gathering information about patients with CRC and treated with targeted agents . Twenty oncology centres in the Czech Republic contributed to this registry . Collected data included patients ’ characteristics , disease history , cancer treatments , response to treatments and safety . Results A total of 148 patients treated with regorafenib in clinical practice were analysed . At regorafenib initiation , almost all patients were fully active or slightly restricted in physical activity . Regorafenib was not administered as first-line treatment in any patient . Median progression-free survival was 3.5 months and median overall survival was 9.3 months . One-year survival rate was 44.6 % . Four partial responses were observed and 51 stable diseases . Progression was observed in 66 patients ( 44.6 % ) . The main reported adverse events were skin toxicity ( 5.4 % ) and fatigue ( 2.0 % ) . Conclusions Regorafenib is a well-established treatment for pretreated patients with mCRC , however real-life data are scarce . Our results demonstrated slightly better efficacy of regorafenib and better safety profile in patients with mCRC compared to the r and omised trials The FDA approved TAS-102 ( Lonsurf ; Taiho Oncology , Inc. ) for the treatment of patients with metastatic colorectal cancer ( mCRC ) who have been previously treated with fluoropyrimidine- , oxaliplatin- , and irinotecan-based chemotherapy ; an anti-VEGF biological therapy ; and if RAS wild type , an anti-EGFR therapy . In an international , multicenter , double-blinded , placebo-controlled trial ( TPU-TAS-102 - 301 , herein referred to as RECOURSE ) , 800 patients with previously treated mCRC were r and omly allocated ( 2:1 ) to receive either TAS-102 35 mg/m2 orally twice daily after meals on days 1 through 5 and 8 through 12 of each 28-day cycle ( n = 534 ) or matching placebo ( n = 266 ) . The trial demonstrated a statistically significant improvement in overall survival for those r and omized to receive TAS-102 , with a median survival of 7.1 months in the TAS-102 arm [ confidence interval ( CI ) , 6.5–7.8 ] and 5.3 months in the placebo arm [ CI , 4.6–6.0 ; hazard ratio ( HR ) , 0.68 ; 95 % CI , 0.58–0.81 ; P < 0.001 , stratified log-rank test ] . The trial also demonstrated a statistically significant prolongation of progression-free survival ( HR , 0.47 ; 95 % CI , 0.40–0.55 ; P < 0.001 ) . The most common adverse reactions , in order of decreasing frequency , observed in the patients who received TAS-102 were anemia , neutropenia , asthenia/fatigue , nausea , thrombocytopenia , decreased appetite , diarrhea , vomiting , abdominal pain , and pyrexia . Adverse events led to discontinuation of TAS-102 in 3.6 % of patients , and 13.7 % required a dose reduction . The most common adverse reactions leading to dose reduction were neutropenia , anemia , febrile neutropenia , fatigue , and diarrhea . Clin Cancer Res ; 23(12 ) ; 2924–7 . © 2017 AACR Output:	Based on efficacy and safety , there was a tendency that fruquintinib was superior to regorafenib , as a whole , regorafenib and fruquintinib demonstrated similar clinical benefit for patients with refractory mCRC . It seems that fruquintinib has less toxic in all- grade toxicity when compared with regorafenib
MS21249	*TASK* the task is to summarize an input biomedical literature in six sentences *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 investigated the differences in the effect of an angiotensin converting enzyme inhibitor ( ACEI ) compared with an angiotensin receptor blocker ( ARB ) on blood pressure ( BP ) and pulse pressure ( PP ) measured in the clinic ( CBP and CPP , respectively ) , at home ( HBP , HPP ) and with ambulatory monitoring ( ABP , APP ) . Twenty-seven hypertensive patients were r and omised to receive lisinopril ( 20 mg ) or losartan ( 50 mg ) for 5 weeks , and were subsequently crossed-over to the alternative treatment for a second 5-week period . Measurements of CBP , 24-h ABP and 5-days HBP were performed before r and omisation and at the end of each treatment period . All measurement methods showed that lisinopril was more effective than losartan in reducing BP . However , the difference between the two drugs was demonstrated with greater precision using HBP ( P<0.001 ) than 24-h ABP ( P<0.01 ) , whereas the poorest precision for demonstrating this difference was provided by CBP ( P<0.05 ) . Lisinopril was also found more effective than losartan in reducing HPP ( P=0.01 ) and 24-h APP ( P=0.03 ) whereas no such a difference was detected using measurements of CPP . It was concluded that the antihypertensive drugs may differ in their effects not only on BP , but also on PP . HBP monitoring appears to be as reliable as 24-h ABP monitoring in detecting differences in the effect of drugs on both BP and PP . Clinic measurements seem to be the least reliable method , particularly in the detection of differences in PP Office , home , and ambulatory blood pressure ( BP ) demonstrate variable associations with outcomes . The authors sought to compare office BP ( OBP ) , home BP ( HBP ) , and ambulatory BP ( ABP ) for measuring responses to hydrochlorothiazide ( HCTZ ) , atenolol , and their combination . After completing washout , eligible patients were r and omized to atenolol 50 mg or HCTZ 12.5 mg daily . Doses were doubled after 3 weeks and the alternate drug was added after 6 weeks if BP was > 120/70 mm Hg ( chosen to allow maximum opportunity to assess genetic associations with dual BP therapy in the parent study ) . OBP ( in triplicate ) , HBP ( twice daily for 5 days ) , and 24-hour ABP were measured at baseline , after monotherapy , and after combination therapy . BP responses were compared between OBP , HBP , and ABP for each monotherapy and combination therapy . In 418 patients , OBP overestimated BP response compared with HBP , with an average 4.6 mm Hg greater reduction in systolic BP ( P<.0001 ) and 2.1 mm Hg greater reduction in diastolic BP ( P<.0001 ) across all therapies . Results were similar for atenolol and HCTZ monotherapy . ABP response was more highly correlated with HBP response ( r=0.58 ) than with OBP response ( r=0.47 ; P=.04 ) . In the context of a r and omized clinical trial , the authors have identified significant differences in HBP , OBP , and ABP methods of measuring BP response to atenolol and HCTZ monotherapy 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 Gender , age , smoking , race , and body mass index have been reported to determine the ambulatory white-coat effect ( WCE ) and white-coat hypertension ( WCH ) . Methods Baseline conventional , day-time ambulatory and self-measured home blood pressure measurements from the THOP trial were used to study the effect of gender , age , body mass index , smoking habits and treatment status on the white-coat syndrome as assessed by ambulatory monitoring or self-measurement . Results The mean systolic/diastolic WCE was 9.1/6.7 mmHg if based on ambulatory blood pressure and 12.2/8.7 mmHg if based on self-measured blood pressure . The ambulatory WCE was significantly higher in women , in older subjects ( 65 + ) , in obese subjects , in non-smokers and in patients on antihypertensive drug treatment . The self-measured WCE was significantly higher in women and in non-smokers . Ambulatory WCH was present in 6.6 % of the untreated patients and 14.2 % had self-measured WCH . The proportion of ambulatory WCH was significantly higher in obese subjects ; the proportion of self-measured WCH did not differ by gender , age , body mass index , or smoking habits . Conclusions The ambulatory white-coat syndrome was determined by gender , age , body mass index , smoking habits , and treatment status . The self-measured white-coat syndrome was greater than the ambulatory white-coat syndrome but depended less on the determinants under study Background —The prevalence and clinical significance of isolated office ( or white coat ) hypertension is controversial , and population data are limited . We studied the prevalence of this condition and its association with echocardiographic left ventricular mass in the general population of the PAMELA ( Pressione Arteriose Monitorate E Loro Associazioni ) Study . Methods and Results —The study involved a large , r and omized sample ( n=3200 ) representative of the Monza ( Milan ) population , 25 to 74 years of age . Participants in the study ( 64 % of the sample ) underwent measurements of office , home , 24-hour ambulatory blood pressure , and echocardiography . Isolated office hypertension was defined as systolic or diastolic values ≥140 mm Hg or ≥90 mm Hg , respectively . Home and ambulatory normotension were defined according to criteria previously established from the PAMELA Study , for example , < 132/83 mm Hg ( systolic/diastolic ) for home and 125/79 mm Hg for 24-hour average blood pressure . Treated hypertensive subjects were excluded from analysis that was made on a total of 1637 subjects . Depending on normotension being established on systolic or diastolic blood pressure measured at home or over 24 hours , the prevalence of isolated office hypertension ranged from 9 % to 12 % . In these subjects , left ventricular mass index was greater ( P < 0.01 ) than in subjects with normotension both in and outside the office . This was the case also for prevalence of left ventricular hypertrophy . Left ventricular mass index and hypertrophy were similarly greater in subjects found to have normal office but elevated home or ambulatory blood pressure ( ≈10 % of the population ) . Conclusions —Isolated office hypertension has a noticeable prevalence in the population and is accompanied by structural cardiac alterations , suggesting that it is not an entirely harmless phenomenon . This is the case also for the opposite condition , that is , normal office but elevated home or ambulatory blood pressure , which implies that limiting blood pressure measurements to office values may not suffice in identification of subjects at risk BACKGROUND Our objective was to assess the value of home blood pressure ( BP ) monitoring in comparison to office BP measurements and ambulatory monitoring in predicting hypertension-induced target-organ damage . METHODS Sixty-eight untreated patients with hypertension with at least two routine pre study office visits were included ( mean age , 48.6 + /- 9.1 [ SD ] years ; 50 men ) . Office BP was measured in two study visits , home BP was measured for 6 workdays , and ambulatory BP was monitored for 24 h. All BP measurements were obtained using vali date d electronic devices . Target-organ damage was assessed by measuring the echocardiographic left-ventricular mass index ( LVMI ) , urinary albumin excretion rate ( AER ) in two overnight urine collection s , and carotid-femoral pulse-wave velocity ( PWV ) ( Complior device ; Colson , Garges-les-Gonesse , Paris , France ) . RESULTS The correlation coefficients of LVMI with office BP were 0.24/0.15 ( systolic/diastolic ) , with home BP 0.35/0.21 ( systolic , P < .01 ) , and with 24-h ambulatory BP 0.23/0.19 , awake 0.21/0.16 , and asleep 0.28/0.26 ( asleep , both P < .05 ) . The correlation coefficients of AER with office BP were 0.24/0.31 ( diastolic , P < .05 ) , with home BP 0.28/0.26 ( both P < .05 ) , and with 24-h ambulatory BP 0.25/0.24 , awake 0.24/0.25 ( diastolic , P < .05 ) , and asleep 0.26/0.18 ( systolic , P < .05 ) . There was a trend for negative correlations between PWV and diastolic BP measurements ( not significant ) . In multiple-regression models assessing independent predictors of each of the three indices of target-organ damage , systolic home BP and age were the only independent predictors of increased LVMI that reached borderline statistical significance . CONCLUSIONS These data suggest that home BP is as reliable as ambulatory monitoring in predicting hypertension-induced target-organ damage , and is superior to carefully taken office measurements BACKGROUND Because of poor patient compliance and clinical inertia , hypertension control rates remain poor . Home blood-pressure measurements ( HBPM ) improve compliance of patients and achievement of blood pressure ( BP ) targets . However , few studies have evaluated self-BP management by patients . METHODS In a multicenter , prospect i ve , single-group , open-label pilot study of 111 patients whose hypertension was uncontrolled despite monotherapy , we studied satisfaction with , and feasibility of , HBPM and self-titration of antihypertensive treatment using telemedicine for compliance , efficacy , and safety . After education ( protocol , action plan , and use of the HBPM device ) , patients performed a sequence of HBPM every 2 weeks for 8 weeks . Following a stepwise approach , treatment was increased by the patient at weeks 4 and 6 if average HBPM values exceeded predefined limits . For each titration , the patient informed the Core Center by telemedicine , but BP values were transferred automatically . RESULTS Overall , 80 % of patients were satisfied ( 58 % ) or very satisfied ( 23 % ) with the program ( 95 % confidence interval , 73 % to 87 % ) . Regarding compliance , 78 % of patients fully complied with self-measurement , and just over 71 % titrated their treatment adequately . Physicians were satisfied ( 52 % ) or very satisfied ( 22 % ) with the program . Between the first and final visits ( at week 8) , office systolic/diastolic BP ( mean + /- SD ) decreased significantly from 151 + /- 9/91 + /- 6 to 143 + /- 13/84 + /- 11 mmHg . During the trial , HBPM ( mean + /- SD ) decreased significantly from 149 + /- 13/86 + /- 12 to 138 + /- 16/81 + /- 10 mmHg . No significant safety issues were reported . CONCLUSIONS This innovative approach to the management of hypertension , combining self-measurement and self-titration , is feasible , well-accepted by both patients and physicians , and safe BACKGROUND Home blood pressure ( BP ) Output:	The studies review ed consistently showed moderate diagnostic agreement between HBPM and ABPM , and superiority of HBPM compared to office measurements in diagnosing uncontrolled hypertension , assessing antihypertensive drug effects and improving patients ' compliance and hypertension control . Preliminary evidence suggests that HBPM has the potential for cost savings . CONCLUSIONS There is conclusive evidence that HBPM is useful for the initial diagnosis and the long-term follow-up of treated hypertension .
MS21250	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Heart failure patients are regularly admitted to hospital and frequently use multiple medication . Besides intentional changes in pharmacotherapy , unintentional changes may occur during hospitalisation . The aim of this study was to investigate the effect of a clinical pharmacist discharge service on medication discrepancies and prescription errors in patients with heart failure . Setting A general teaching hospital in Tilburg , the Netherl and s. Method An open r and omized intervention study was performed comparing an intervention group , with a control group receiving regular care by doctors and nurses . The clinical pharmacist discharge service consisted of review of discharge medication , communicating prescribing errors with the cardiologist , giving patients information , preparation of a written overview of the discharge medication and communication to both the community pharmacist and the general practitioner about this medication . Within 6 weeks after discharge all patients were routinely scheduled to visit the outpatient clinic and medication discrepancies were measured . Main outcome measure The primary endpoint was the frequency of prescription errors in the discharge medication and medication discrepancies after discharge combined . Results Forty-four patients were included in the control group and 41 in the intervention group . Sixty-eight percent of patients in the control group had at least one discrepancy or prescription error against 39 % in the intervention group ( RR 0.57 ( 95 % CI 0.37–0.88 ) ) . The percentage of medications with a discrepancy or prescription error in the control group was 14.6 % and in the intervention group it was 6.1 % ( RR 0.42 ( 95 % CI 0.27–0.66 ) ) . Conclusion This clinical pharmacist discharge service significantly reduces the risk of discrepancies and prescription errors in medication of patients with heart failure in the 1st month after discharge 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 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 Context Research on patient safety has focused on adverse events in hospitalized patients . Adverse events following hospitalization have received little attention . Contribution Among 400 consecutive patients discharged from the general medical service of an academic hospital , 76 had adverse events during the 2 weeks following hospital discharge . Of the adverse events , the research ers categorized 23 as preventable , 24 as ameliorable , and the remainder as neither . Adverse drug events were the most frequent occurrence . Implication s Interventions to maximize patient safety should consider the vulnerable transition from hospital to home . The Editors Patient safety is a public concern that has received substantial attention , especially since the release of two reports from the U.S. Institute of Medicine . The first of these , To Err Is Human , review ed the literature on adverse events , or injuries result ing from medical care ( 1 ) . On the basis of data from two large population -based chart review studies , the report estimated that adverse events occur in 2.9 % ( 2 ) to 3.7 % ( 3 ) of hospitalizations . The first of these studies ( 2 ) found that although most injuries are minor , approximately 1 in 10 results in death . The research ers determined that approximately half of the adverse events were caused by errors ( 1 , 3 , 4 ) . The second report , Crossing the Quality Chasm , which proposes strategies for improving the health system , declared patient safety a fundamental component of care quality ( 5 ) . However , the estimated incidence of adverse events quoted in To Err Is Human may underestimate the overall safety problem , since injuries occurring after discharge were not included in the evaluation . Patients may be especially vulnerable to injuries during this period because they may still have functional impairments and because discontinuities may occur at the interface of acute and ambulatory care ( 6 ) . These discontinuities may be worsened by the current health care environment , in which patients are leaving the hospital quicker and sicker ( 7 ) and may receive care from hospitalists rather than their primary care physicians ( 8) . Despite these theoretical concerns , few studies are available to estimate the extent of the problem . Several studies have determined the risk for postdischarge wound infections in surgical patients ( 9 , 10 ) , but this is a specific type of safety problem and the risk can not be generalized . Other studies have used readmission rates to identify poor- quality hospital care ( 11 ) . However , this outcome is an insensitive and nonspecific marker of quality in general ( 11 ) and safety in particular . Information on the incidence and type of adverse events is vital for improving postdischarge safety . We wanted to determine the incidence and severity of adverse events affecting patients after discharge from the hospital to home . In addition , we wanted to identify the incidence of preventable and ameliorable adverse events , classify types of adverse events , and identify system improvements to reduce the incidence and severity of adverse events after discharge . Methods Overview To determine the rate of adverse events , we first created a case summary of every patient 's posthospital course by performing a medical record review and a telephone interview approximately 3 weeks after discharge . Using this information , we created event summaries , which two board-certified internists independently review ed to determine whether medical management caused an injury and , if so , whether it was preventable or ameliorable . The institutional review board at the study hospital approved the protocol . Definitions Adverse outcomes were any of the following patient experiences after discharge : new or worsening symptoms , unanticipated visits to health facilities for tests or treatments , or death . An adverse event was an injury result ing from medical management rather than the underlying disease . We evaluated all injuries result ing in symptoms after discharge , regardless of when the events occurred . Thus , we included adverse events that occurred in the hospital and after discharge as long as symptoms persisted until the patient went home . A preventable adverse event was an injury that could have been avoided , that is , an injury judged to probably be the result of an error or a system design flaw . An ameliorable adverse event was an injury whose severity could have been substantially reduced if different actions or procedures had been performed or followed . Patient Sample We used a prospect i ve cohort design to study adult medical patients at an 800-bed urban academic teaching hospital . Patients were included if they went home from the general medical service during a sequential 81-day period , had telephone service , and could complete a telephone interview in English . Patient surrogates were permitted to complete the interview if the patient could not . Telephone Interview A board-certified internist contacted patients by telephone within 2 to 5 weeks of discharge . If the patient was eligible and consented , he or she underwent a semi-structured interview over the telephone . If the patient was not available , we made up to 20 attempts to contact him or her at different times of the day and week . If the patient declined to participate or we were unable to contact him or her after 5 weeks , we rated the patient as a nonresponder . Responders underwent a telephone interview that had several components ( Appendix Figure ) . The principal component assessed the patient 's condition since discharge by using a full review of organ systems . If patients answered yes to any question , the interviewer asked them to elaborate about the symptom 's severity , timing in relation to hospitalization and treatments , and resolution . The survey also determined patients ' use of health services since discharge , including home care services , physician services , visits to laboratories , and readmissions to the hospital . Preparation of Case Summaries To create a case summary , the internist combined the information from the telephone interview with information obtained from a review of the patient 's electronic medical record . This computerized clinical record contains h and over notes from the hospitalization ; discharge summaries ; previous orders and written instructions ; emergency department and clinic notes ; operative and procedure notes ; and all laboratory results , including results of radiography , electrocardiography , and pathologic examination . If necessary , the paper chart was also review ed to clarify information that was in the discharge summary or h and over notes . If patients returned to the study hospital after discharge , we were able to vali date their history by review ing their records . However , for patients receiving care elsewhere , we had to rely on firsth and accounts . Preparation of Event Summaries The internist review ed every patient 's case summary for adverse outcomes . If any were found , an event summary that consisted of a detailed description of each outcome , including its onset , its severity , the health services used during its treatment , and its resolution , was created for each one . If there were no adverse outcomes , then the event summary consisted of the case summary . Determination of Adverse Events Two other board-certified internists independently rated each event summary by using st and ard techniques as described elsewhere ( 3 ) . Each event summary was evaluated separately . Review ers first rated on a scale of 1 to 6 their confidence that medical management caused an injury . If their rating was 5 or 6 , indicating that the injury was probably or definitely caused by management , the event was considered an adverse event . For adverse events , the internists used implicit criteria to determine their preventability and ameliorability . The two review ers ' assessment s were then compared for causality , preventability , and ameliorability . If there was disagreement , the two review ers discussed the case to attempt to come to consensus . If they did not agree , a third board-certified internist rated the event independently . Next , review ers rated injury severity , health services used , type of injury , and location . Injury severity was categorized as serious laboratory abnormality only , one day of symptoms , several days of symptoms , nonpermanent disability , permanent disability , or death . Differentiation between several days of symptoms and nonpermanent disability relied on evidence that symptoms interfered with patients ' activities of daily living . We categorized health services used as none , additional visit to a physician , additional visit for laboratory testing in addition to a physician visit , visit to an emergency department , readmission to the hospital , or death . We were able to determine whether health services were additional because during the interview we asked whether the health service was arranged before discharge or specifically for the particular symptom . We used a st and ard approach to classify the type of injury ( 2 , 3 ) , categorizing each as an adverse drug event , a procedure-related injury , a nosocomial infection , a fall , or other . We also classified the location of adverse events . Our primary objective was to evaluate adverse events affecting patients after discharge from the hospital to home . We felt that most of these events would occur after the patient went home , but we recognized a priori that some adverse events could occur in the hospital but lead to morbidity after discharge because of the severity of the injury or because health providers did not recognize the problem at discharge . Examples of injuries occurring in the hospital but affecting patients after discharge include pressure ulcers , missed diagnoses , and erroneous drug prescriptions . If it was determined that the adverse event occurred in the hospital , we examined whether the injury was recognized before discharge and , if so , whether definitive management was instituted at that time . To develop strategies UNLABELLED The purpose of this paper Output:	Statistically significant effects were mostly found in reducing hospital use ( for example , rehospitalizations ) , improvement of continuity of care ( for example , accurate discharge information ) , and improvement of patient status after discharge ( for example , satisfaction ) . Many interventions have positive effects on patient care . However , given the complexity of interventions and outcome measures , the literature does not permit firm conclusions about which interventions have these effects .
MS21251	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE . The study tested whether a combined environmental and educational intervention solely promoting water consumption was effective in preventing overweight among children in elementary school . METHODS . The participants in this r and omized , controlled cluster trial were second- and third- grade rs from 32 elementary schools in socially deprived areas of 2 German cities . Water fountains were installed and teachers presented 4 prepared classroom lessons in the intervention group schools ( N = 17 ) to promote water consumption . Control group schools ( N = 15 ) did not receive any intervention . The prevalence of overweight ( defined according to the International Obesity Task Force criteria ) , BMI SD scores , and beverage consumption ( in glasses per day ; 1 glass was defined as 200 mL ) self-reported in 24-hour recall question naires , were determined before ( baseline ) and after the intervention . In addition , the water flow of the fountains was measured during the intervention period of 1 school year ( August 2006 to June 2007 ) . RESULTS . Data on 2950 children ( intervention group : N = 1641 ; control group : N = 1309 ; age , mean ± SD : 8.3 ± 0.7 years ) were analyzed . After the intervention , the risk of overweight was reduced by 31 % in the intervention group , compared with the control group , with adjustment for baseline prevalence of overweight and clustering according to school . Changes in BMI SD scores did not differ between the intervention group and the control group . Water consumption after the intervention was 1.1 glasses per day greater in the intervention group . No intervention effect on juice and soft drink consumption was found . Daily water flow of the fountains indicated lasting use during the entire intervention period , but to varying extent . CONCLUSION . Our environmental and educational , school-based intervention proved to be effective in the prevention of overweight among children in elementary school , even in a population from socially deprived areas BACKGROUND The consumption of beverages that contain sugar is associated with overweight , possibly because liquid sugars do not lead to a sense of satiety , so the consumption of other foods is not reduced . However , data are lacking to show that the replacement of sugar-containing beverages with noncaloric beverages diminishes weight gain . METHODS We conducted an 18-month trial involving 641 primarily normal-weight children from 4 years 10 months to 11 years 11 months of age . Participants were r and omly assigned to receive 250 ml ( 8 oz ) per day of a sugar-free , artificially sweetened beverage ( sugar-free group ) or a similar sugar-containing beverage that provided 104 kcal ( sugar group ) . Beverages were distributed through schools . At 18 months , 26 % of the children had stopped consuming the beverages ; the data from children who did not complete the study were imputed . RESULTS The z score for the body-mass index ( BMI , the weight in kilograms divided by the square of the height in meters ) increased on average by 0.02 SD units in the sugar-free group and by 0.15 SD units in the sugar group ; the 95 % confidence interval ( CI ) of the difference was -0.21 to -0.05 . Weight increased by 6.35 kg in the sugar-free group as compared with 7.37 kg in the sugar group ( 95 % CI for the difference , -1.54 to -0.48 ) . The skinfold-thickness measurements , waist-to-height ratio , and fat mass also increased significantly less in the sugar-free group . Adverse events were minor . When we combined measurements at 18 months in 136 children who had discontinued the study with those in 477 children who completed the study , the BMI z score increased by 0.06 SD units in the sugar-free group and by 0.12 SD units in the sugar group ( P=0.06 ) . CONCLUSIONS Masked replacement of sugar-containing beverages with noncaloric beverages reduced weight gain and fat accumulation in normal-weight children . ( Funded by the Netherl and s Organization for Health Research and Development and others ; DRINK Clinical Trials.gov number , NCT00893529 . ) OBJECTIVE : To examine the long-term relationship between changes in water and beverage intake and weight change . SUBJECTS : Prospect i ve cohort studies of 50 013 women aged 40–64 years in the Nurses ’ Health Study ( NHS , 1986–2006 ) , 52 987 women aged 27–44 years in the NHS II ( 1991–2007 ) and 21 988 men aged 40–64 years in the Health Professionals Follow-up Study ( 1986–2006 ) without obesity and chronic diseases at baseline . MEASURES : We assessed the association of weight change within each 4-year interval , with changes in beverage intakes and other lifestyle behaviors during the same period . Multivariate linear regression with robust variance and accounting for within-person repeated measures were used to evaluate the association . Results across the three cohorts were pooled by an inverse-variance-weighted meta- analysis . RESULTS : Participants gained an average of 1.45 kg ( 5th to 95th percentile : −1.87 to 5.46 ) within each 4-year period . After controlling for age , baseline body mass index and changes in other lifestyle behaviors ( diet , smoking habits , exercise , alcohol , sleep duration , TV watching ) , each 1 cup per day increment of water intake was inversely associated with weight gain within each 4-year period ( −0.13 kg ; 95 % confidence interval ( CI ) : −0.17 to −0.08 ) . The associations for other beverages were : sugar-sweetened beverages ( SSBs ) ( 0.36 kg ; 95 % CI : 0.24–0.48 ) , fruit juice ( 0.22 kg ; 95 % CI : 0.15–0.28 ) , coffee ( −0.14 kg ; 95 % CI : −0.19 to −0.09 ) , tea ( −0.03 kg ; 95 % CI : −0.05 to −0.01 ) , diet beverages ( −0.10 kg ; 95 % CI : −0.14 to −0.06 ) , low-fat milk ( 0.02 kg ; 95 % CI : −0.04 to 0.09 ) and whole milk ( 0.02 kg ; 95 % CI : −0.06 to 0.10 ) . We estimated that replacement of 1 serving per day of SSBs by 1 cup per day of water was associated with 0.49 kg ( 95 % CI : 0.32–0.65 ) less weight gain over each 4-year period , and the replacement estimate of fruit juices by water was 0.35 kg ( 95 % CI : 0.23–0.46 ) . Substitution of SSBs or fruit juices by other beverages ( coffee , tea , diet beverages , low-fat and whole milk ) were all significantly and inversely associated with weight gain . CONCLUSION : Our results suggest that increasing water intake in place of SSBs or fruit juices is associated with lower long-term weight gain OBJECTIVE To determine the efficacy of a 2-year obesity prevention program in African American girls . DESIGN Memphis GEMS ( Girls ' health Enrichment Multi-site Studies ) was a controlled trial in which girls were r and omly assigned to an obesity prevention program or alternative intervention . SETTING Local community centers and YWCAs ( Young Women 's Christian Associations ) in Memphis , Tennessee . PARTICIPANTS Girls aged 8 to 10 years ( N = 303 ) who were identified by a parent or guardian as African American and who had a body mass index ( BMI ) at or higher than the 25th percentile for age or 1 parent with a BMI of 25 or higher . INTERVENTIONS Group behavioral counseling to promote healthy eating and increased physical activity ( obesity prevention program ) or self-esteem and social efficacy ( alternative intervention ) . MAIN OUTCOME MEASURE The BMI at 2 years . RESULTS The BMI increased in all girls with no treatment effect ( obesity prevention minus alternative intervention ) at 2 years ( mean , 0.09 ; 95 % confidence interval [ CI ] , -0.40 to 0.58 ) . Two-year treatment effects in the expected direction were observed for servings per day of sweetened beverages ( mean , -0.19 ; 95 % CI , -0.39 to 0.09 ) , water ( mean , 0.21 ; 95 % CI , 0.03 to 0.40 ) , and vegetables ( mean , 0.15 ; 95 % CI,-0.02 to 0.30 ) , but there were no effects on physical activity . Post hoc analyses suggested a treatment effect in younger girls ( P for interaction = .08 ) . The mean BMI difference at 2 years was -2.41 ( 95 % CI , -4.83 to 0.02 ) in girls initially aged 8 years and -1.02 ( 95 % CI , -2.31 to 0.27 ) in those initially aged 10 years . CONCLUSIONS The lack of significant BMI change at 2 years indicates that this intervention alone is insufficient for obesity prevention . Effectiveness may require more explicit behavior change goals and a stronger physical activity component as well as supportive changes in environmental context CONTEXT Recently , we showed that drinking 500 ml water induces thermogenesis in normal-weight men and women . OBJECTIVE We now repeated these studies in a r and omized , controlled , crossover trial in overweight or obese otherwise healthy subjects ( eight men and eight women ) , comparing also the effects of 500 ml isoosmotic saline or 50 ml water . RESULTS Only 500 ml water increased energy expenditure by 24 % over the course of 60 min after ingestion , whereas isoosmotic saline and 50 ml water had no effect . Heart rate and blood pressure did not change in these young , healthy subjects . CONCLUSIONS Our data exclude volume-related effects or gastric distension as the mediator of the thermogenic response to water drinking . Instead , we hypothesize the existence of a portal osmoreceptor , most likely an ion channel OBJECTIVE To determine whether an educational programme aim ed at discouraging students from drinking sugar-sweetened beverages could prevent excessive weight gain . DESIGN Forty-seven classes in twenty-two schools were r and omised as intervention or control . SUBJECTS Participants were 1140 , 9 - 12-year-old fourth grade rs ( 435 in the intervention group and 608 in the control group ) . Sugar-sweetened beverages and juice intake were measured through one 24 h recall at baseline and another at the end of the trial . The main outcome was the change in BMI ( BMI = weight (kg)/height ( m2 ) ) , measured at the beginning and at the end of the school year . Intention-to-treat analysis was performed taking into account the cluster ( classes ) effect . RESULTS A statistically significant decrease in the daily consumption of carbonated drinks in the intervention compared to control ( mean difference = -56 ml ; 95 % CI -119 , -7 ml ) was followed by a non-significant overall reduction in BMI , P = 0.33 . However , among those students overweight at baseline , the intervention group showed greater BMI reduction ( -0.4 kg/m2 compared with -0.2 kg/m2 in the control group ( P = 0.11 ) ) , and this difference was statistically significant among girls ( P = 0.009 ) . Fruit juice consumption was slightly increased in the intervention group ( P = 0.08 ) , but not among girls . CONCLUSION Decreasing sugar-sweetened beverages intake significantly reduced BMI among overweight children , and mainly among girls . Efforts to reduce energy intake through liquids need to emphasise overall sweetened beverages and addition of sugar on juices OBJECTIVE We examined whether drinking water per se is associated with drinking less of other beverages and whether changes in BMI are associated with the intake of water and other beverages . DESIGN Secondary analysis of a r and omized trial of fourth grade rs followed over 1 year . SETTING Public schools in the metropolitan area of Rio de Janeiro , Brazil . SUBJECTS Participants were 1134 students aged 10 - 11 years . RESULTS At baseline , a higher frequency of water consumption was associated with a greater daily intake of fruit juice ( P = 0.02 ) and a higher daily frequency of milk ( P = 0.005 ) . In the intervention group , the baseline frequency of water consumption was negatively associated with weight change over 1 year but without statistical significance ( coefficient = -0.08 kg/m2 ; 95 % CI -0.37 , 0.24 kg/m2 ) , whereas fruit juice intake frequency was positively associated with weight change : each increase in fruit juice intake of 1 glass/d was associated with a BMI increase of 0.16 ( 95 % CI 0.02 , 0.30 ) kg/m2 . CONCLUSIONS Our findings do not support a protective effect of water consumption on BMI , but confirm consumption of juice drinks as a risk factor for BMI gain . Students who reported high water consumption also reported high intake of other beverages ; therefore , the promotion of water consumption per se would not prevent excessive weight gain Obesity among Saudi youth is a growing public health challenge . This cross-sectional study measured body mass index ( BMI ) and determined the eating habits and lifestyle of 107 r and omly selected female adolescent students ( age Output:	On the cross-sectional level , higher water consumption seems to be associated with higher weight status . In contrast , longitudinal studies suggest a weight-reducing effect of water consumption , but evidence for a causal association is still low
MS21252	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Changing dietary and physical activity habits has the potential to postpone or prevent the development of type 2 diabetes . However , it needs to be assessed whether moderate interventions , in agreement with current guidelines for the general population , are effective . We evaluated the impact of a 2-year combined diet and physical activity intervention program on glucose tolerance in Dutch subjects at increased risk for developing diabetes . RESEARCH METHODS AND PROCEDURES Subjects with glucose intolerance were r and omly assigned to either the lifestyle intervention group ( INT ) or control group ( CON ) . The INT received regular dietary advice and was stimulated to increase their physical activity . The CON received a brief leaflet about healthy diet and increased physical activity . Primary outcome measure was the change in glucose tolerance . RESULTS In total , 88 subjects completed 2 years of intervention ( 40 subjects in the INT , 48 subjects in the CON , mean BMI 29.4 kg/m2 ) . Subjects in the INT reduced their body weight , waist circumference , and ( saturated ) fat intake and improved their aerobic capacity . Two-hour plasma glucose concentration declined from 8.7 to 8.0 mM in the INT and rose from 8.6 to 9.4 mM in the CON ( p < 0.01 ) . Subjects adherent to both the diet and exercise intervention showed the largest reduction in 2-hour glucose levels . DISCUSSION Our results showed that a lifestyle intervention program according to general recommendations improves glucose tolerance , even in a less obese and more physical active population . Furthermore , our results underscore the importance of combining diet and physical activity to improve glucose tolerance and insulin resistance Lifestyle modification reduces the risk of developing type 2 diabetes and may have its effect through improving insulin sensitivity , beta-cell function , or both . To determine whether diet and exercise improve insulin sensitivity and /or beta-cell function and to evaluate these effects over time , we quantified insulin sensitivity and the acute insulin response to glucose ( AIRg ) in 62 Japanese Americans ( age 56.5 + /- 1.3 years ; mean + /- SE ) with impaired glucose tolerance ( IGT ) who were r and omized to the American Heart Association ( AHA ) Step 2 diet plus endurance exercise ( n = 30 ) versus the AHA Step 1 diet plus stretching ( n = 32 ) for 24 months . beta-Cell function ( disposition index [ DI ] ) was calculated as S(i ) x AIRg , where S(i ) is the insulin sensitivity index . The incremental area under the curve for glucose ( incAUCg ) was calculated from a 75-g oral glucose tolerance test . Intra-abdominal fat ( IAF ) and subcutaneous fat ( SCF ) areas were measured by computed tomography . At 24 months , the Step 2/endurance group had lower weight ( 63.1 + /- 2.4 vs. 71.3 + /- 2.9 kg ; P = 0.004 ) and IAF ( 75.0 + /- 7.9 vs. 112.7 + /- 10.4 cm(2 ) ; P = 0.03 ) and SCF ( 196.5 + /- 18.0 vs. 227.7 + /- 19.9 cm(2 ) ; P < 0.001 ) areas , greater S(i ) ( 4.7 + /- 0.5 vs. 3.3 + /- 0.3 x 10(-5 ) min . pmol(-1 ) . l(-1 ) ; P = 0.01 ) , and a trend toward lower AIRg ( 294.9 + /- 50.0 vs. 305.4 + /- 30.0 pmol/l ; P = 0.06 ) and incAUCg ( 8,217.3 + /- 350.7 vs. 8,902.0 + /- 367.2 mg . dl(-1 ) . 2 h(-1 ) ; P = 0.08 ) compared with the Step 1/stretching group after adjusting for baseline values . There was no difference in the DI ( P = 0.7 ) between the groups . S(i ) was associated with changes in weight ( r = -0.426 , P = 0.001 ) and IAF ( r = -0.395 , P = 0.003 ) and SCF ( r = -0.341 , P = 0.01 ) areas . Thus , the lifestyle modifications decreased weight and central adiposity and improved insulin sensitivity in Japanese Americans with IGT . However , such changes did not improve beta-cell function , suggesting that this degree of lifestyle modifications may be limited in preventing type 2 diabetes over the long term Prevention of type 2 diabetes by intensive lifestyle intervention design ed to achieve and maintain ideal body weight was assessed in subjects with impaired glucose tolerance ( IGT ) . Male subjects with IGT recruited from health-screening examinees were r and omly assigned in a 4:1 ratio to a st and ard intervention group ( control group ) and intensive intervention group ( intervention group ) . The final numbers of subjects were 356 and 102 , respectively . The subjects in the control group and in the intervention group were advised to maintain body mass index ( BMI ) of < 24.0 kg/m2 and of < 22.0 kg/m2 , respectively , by diet and exercise . In the intervention group , detailed instructions on lifestyle were repeated every 3 - 4 months during hospital visits . Diabetes was judged to have developed when two or more consecutive fasting plasma glucose ( FPG ) values exceeded 140 mg/dl . A 100 g oral glucose tolerance test was performed every 6 months to detect improvement of glucose tolerance . The subjects were seen in an ordinary outpatient clinic . The cumulative 4-year incidence of diabetes was 9.3 % in the control group , versus 3.0 % in the intervention group , and the reduction in risk of diabetes was 67.4 % ( P < 0.001 ) . Body weight decreased by 0.39 kg in the control group and by 2.18 kg in the intervention group ( P < 0.001 ) . The control group was subclassified according to increase and decrease in body weight . The incidence of diabetes was positively correlated with the changes in body weight , and the improvement in glucose tolerance was negatively correlated . Subjects with higher FPG at baseline developed diabetes at a higher rate than those with lower FPG . Higher 2h plasma glucose values and higher BMI values at baseline were also associated with a higher incidence of diabetes , but the differences were not significant . Subjects with a low insulinogenic index ( DeltaIRI/DeltaPG 30 min after an oral glucose load ) developed diabetes at a significantly higher rate than those with a normal insulinogenic index . Comparison of the BMI data and incidence of diabetes in five diabetes prevention studies by lifestyle intervention revealed a linear correlation between the incidence of diabetes and the BMI values , with the exception of the DaQing Study . However , the slope of the reduction in incidence of diabetes in the intensive intervention groups was steeper than expected simply on the basis of the reduction of BMI , suggesting that the effect of lifestyle intervention can not be solely ascribed to the body weight reduction . We conclude that lifestyle intervention aim ed at achieving ideal body weight in men with IGT is effective and can be conducted in an outpatient clinic setting Risk factors associated with the progression from impaired glucose tolerance ( IGT ) to NIDDM were examined in data from six prospect i ve studies . IGT and NIDDM were defined in all studies by World Health Organization ( WHO ) criteria , and baseline risk factors were measured at the time of first recognition of IGT . The studies varied in size from 177 to 693 participants with IGT , and included men and women followed from 2 to 27 years after the recognition of IGT . Across the six studies , the incidence rate of NIDDM was 57.2/1,000 person-years and ranged from 35.8/1,000 to 87.3/1,000 person-years . Although baseline measures of fasting and 2-h postchallenge glucose levels were both positively associated with NIDDM incidence , incidence rates were sharply higher for those in the top quartile of fasting plasma glucose levels , but increased linearly with increasing 2-h postchallenge glucose quartiles . Incidence rates were higher among the Hispanic , Mexican-American , Pima , and Nauruan population s than among Caucasians . The effect of baseline age on NIDDM incidence rates differed among the studies ; the rates did not increase or rose only slightly with increasing baseline age in three of the studies and formed an inverted U in three studies . In all studies , estimates of obesity ( including BMI , waist-to-hip ratio , and waist circumference ) were positively associated with NIDDM incidence . BMI was associated with NIDDM incidence independently of fasting and 2-h post challenge glucose levels in the combined analysis of all six studies and in three cohorts separately , but not in the three studies with the highest NIDDM incidence rates . Sex and family history of diabetes were generally not related to NIDDM progression . This analysis indicates that persons with IGT are at high risk and that further refinement of risk can be made by other simple measurements . The ability to identify persons at high risk of NIDDM should facilitate clinical trials in diabetes prevention The aim of the Finnish Diabetes Prevention Study is to assess the efficacy of an intensive diet-exercise programme in preventing or delaying type 2 diabetes in individuals with impaired glucose tolerance ( IGT ) and to evaluate the effect of the programme on the risk factors of atherosclerotic vascular diseases and the incidence of cardiovascular events . In this ongoing study , a total of 523 overweight subjects with IGT based on two oral glucose tolerance tests were r and omized to either an intervention group or a control group . The main measure in the intervention group is individual dietary advice aim ed at reducing weight and intake of saturated fat and increasing intake of dietary fibre . The intervention subjects are individually guided to increase their level of physical activity . The control group receives general information about the benefits of weight reduction , physical activity and healthy diet in the prevention of diabetes . A pilot study began in 1993 , and recruitment ended in 1998 . By the end of April 1999 there were 65 new cases of diabetes , 34 drop-outs and one death . The weight reduction was greater ( -4.6 kg ) at 1 year in the intervention group ( n = 152 ) than in the control group ( n = 143 , -0.9 kg , P < 0.0001 ) , and this difference was sustained in the second year of follow-up . At 1 year 43.4 % and at 2 years 41.8 % of the intervention subjects had achieved a weight reduction of at least 5 kg , while the corresponding figures for the control subjects were 14.0 and 12.0 % ( P < 0.001 between the groups ) . At 1 year the intervention group showed significantly greater reductions in 2 h glucose , fasting and 2 h insulin , systolic and diastolic blood pressure , and serum triglycerides . Most of the beneficial changes in cardiovascular risk factors were sustained for 2 years . These interim results of the ongoing Finnish Diabetes Prevention Study demonstrate the efficacy and feasibility of the lifestyle intervention programme OBJECTIVE To describe the 1 ) lifestyle intervention used in the Finnish Diabetes Prevention Study , 2 ) short- and long-term changes in diet and exercise behavior , and 3 ) effect of the intervention on glucose and lipid metabolism . RESEARCH DESIGN AND METHODS There were 522 middle-aged , overweight subjects with impaired glucose tolerance who were r and omized to either a usual care control group or an intensive lifestyle intervention group . The control group received general dietary and exercise advice at baseline and had an annual physician 's examination . The subjects in the intervention group received additional individualized dietary counseling from a nutritionist . They were also offered circuit-type resistance training sessions and advised to increase overall physical activity . The intervention was the most intensive during the first year , followed by a maintenance period . The intervention goals were to reduce body weight , reduce dietary and saturated fat , and increase physical activity and dietary fiber . RESULTS The intervention group showed significantly greater improvement in each intervention goal . After 1 and 3 years , weight reductions were 4.5 and 3.5 kg in the intervention group and 1.0 and 0.9 kg in the control group , respectively . Measures of glycemia and lipemia improved more in the intervention group . CONCLUSIONS The intensive lifestyle intervention produced long-term beneficial changes in diet , physical activity , and clinical and biochemical parameters and reduced diabetes risk . This type of intervention is a feasible option to prevent type 2 diabetes and should be implemented in the primary health care system Clinical trials have demonstrated that lifestyle changes can prevent type 2 diabetes , but the importance of leisure-time physical activity ( LTPA ) is still unclear . We carried out post hoc analyses on the role of LTPA in preventing type 2 diabetes in 487 men and women with impaired glucose tolerance who had completed 12-month LTPA question naires . The subjects were participants in the Finnish Diabetes Prevention Study , a r and omized controlled trial of lifestyle changes including diet , weight loss , and LTPA . There were 107 new cases of diabetes during the 4.1-year Output:	In the four studies that measured the incidence of diabetes as an outcome , the risk of diabetes was reduced by approximately 50 % ( range 42–63 % ) ; as these studies reported only small changes in physical activity levels , the reduced risk of diabetes is likely to be attributable to factors other than physical activity . These results indicate that the contribution of physical activity independent of dietary or weight loss changes to the prevention of type 2 diabetes in people with prediabetes is equivocal
MS21253	*TASK* the task is to summarize an input biomedical literature in six sentences *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 current study aim ed to examine the changes following a sleep hygiene intervention on sleep hygiene practice s , sleep quality , and daytime symptoms in youth . Methods Participants aged 10–18 years with self-identified sleep problems completed our age-appropriate F.E.R.R.E.T ( an acronym for the categories of Food , Emotions , Routine , Restrict , Environment and Timing ) sleep hygiene programme ; each category has three simple rules to encourage good sleep . Participants ( and parents as appropriate ) completed the Adolescent Sleep Hygiene Scale ( ASHS ) , Pittsburgh Sleep Quality Index ( PSQI ) , Sleep Disturbance Scale for Children ( SDSC ) , Pediatric Daytime Sleepiness Scale ( PDSS ) , and wore Actical ® monitors twice before ( 1 and 2 weeks ) and three times after ( 6 , 12 and 20 weeks ) the intervention . Anthropometric data were collected two weeks before and 20 weeks post-intervention . Results Thirty-three youths ( mean age 12.9 years ; M/F = 0.8 ) enrolled , and retention was 100 % . ASHS scores significantly improved ( p = 0.005 ) from a baseline mean ( SD ) of 4.70 ( 0.41 ) to 4.95 ( 0.31 ) post-intervention , as did PSQI scores [ 7.47 ( 2.43 ) to 4.47 ( 2.37 ) ; p < 0.001 ] and SDSC scores [ 53.4 ( 9.0 ) to 39.2 ( 9.2 ) ; p < 0.001 ] . PDSS scores improved from a baseline of 16.5 ( 6.0 ) to 11.3 ( 6.0 ) post- intervention ( p < 0.001 ) . BMI z-scores with a baseline of 0.79 ( 1.18 ) decreased significantly ( p = 0.001 ) post-intervention to 0.66 ( 1.19 ) . Despite these improvements , sleep duration as estimated by Actical accelerometry did not change . There was however a significant decrease in daytime sedentary/light energy expenditure . Conclusions Our findings suggest the F.E.R.R.E.T sleep hygiene education programme might be effective in improving sleep in children and adolescents . However because this was a before and after study and a pilot study with several limitations , the findings need to be addressed with caution , and would need to be replicated within a r and omised controlled trial to prove efficacy . Trial registration Australian New Zeal and Clinical Trials Registry : Background Sufficient sleep during childhood is essential to ensure a transition into a healthy adulthood . However , chronic sleep loss continues to increase worldwide . In this context , it is imperative to make sleep a high-priority and take action to promote sleep health among children . The present series of studies aim ed to shed light on sleep patterns , on the longitudinal association of sleep with school performance , and on practical intervention strategy for Chinese school-aged children . Methods and Findings A serial sleep research es , including a national cross-sectional survey , a prospect i ve cohort study , and a school-based sleep intervention , were conducted in China from November 2005 through December 2009 . The national cross-sectional survey was conducted in 8 cities and a r and om sample of 20,778 children aged 9.0±1.61 years participated in the survey . The five-year prospect i ve cohort study included 612 children aged 6.8±0.31 years . The comparative cross-sectional study ( baseline : n = 525 , aged 10.80±0.41 ; post-intervention follow-up : n = 553 , aged 10.81±0.33 ) was undertaken in 6 primary schools in Shanghai . A battery of parent and teacher reported question naires were used to collect information on children ’s sleep behaviors , school performance , and sociodemographic characteristics . The mean sleep duration was 9.35±0.77 hours . The prevalence of daytime sleepiness was 64.4 % ( sometimes : 37.50 % ; frequently : 26.94 % ) . Daytime sleepiness was significantly associated with impaired attention , learning motivation , and particularly , academic achievement . By contrast , short sleep duration only related to impaired academic achievement . After delaying school start time 30 minutes and 60 minutes , respectively , sleep duration correspondingly increased by 15.6 minutes and 22.8 minutes , respectively . Moreover , intervention significantly improved the sleep duration and daytime sleepiness . Conclusions Insufficient sleep and daytime sleepiness commonly existed and positively associated with the impairment of school performance , especially academic achievement , among Chinese school-aged children . The effectiveness of delaying school staring time emphasized the benefits of optimal school schedule regulation to children ’s sleep health A total of 36 toddlers and preschool children exhibiting bedtime tantrum activity were r and omly assigned to one of three groups : positive routines , graduated extinction , or control . Positive routines involved changing the child 's bedtime to coincide with when he naturally fell asleep , as well as parent and child engaging in a series of four to seven enjoyable activities before the child being placed in bed . During the treatment period , bedtimes were systematic ally scheduled earlier such that the child went to bed at the time parents had originally used . Graduated extinction consisted of the parent putting the child to bed and ignoring the tantrum activity for increasingly longer amounts of time throughout the treatment . Children in these two treatment groups had tantrums less frequently and for shorter periods than control subjects during 6 weeks of treatment and during two follow-up observations 3 and 6 weeks after treatment . Although both treatments were more effective than waiting for the child to outgrow this problem , parents of the positive routine group reported significantly improved marital satisfaction , suggesting additional benefits of this treatment strategy Abstract ObjectiveS leep deprivation among teens is a major health issue . Only 15 % of teens get 8.5 h of sleep on school nights . Sleep deprivation can lead to poor grade s , sleepiness and moodiness . We undertook a study to assess the prevalence of sleep habit disturbance among elementary school students in South Texas with Hispanic ethnicity predominance . We also found how much a video based on sleep education had an impact on these children . Method Once the Corpus Christi Independent School District ( CCISD ) approved the collection of baseline sleep data , question naires were administered using the Children ’s Sleep Habit Question naire ( CSHQ . ) These question naires were distributed prior to the viewing of the educational and animated movie KNIGHTS ( Keep Nurturing and Inspiring Good Habits in Teen Sleep ) . Four months later , a r and om follow-up was performed and the children were requested to respond to the same CSHQ . Results 264 children from two elementary schools participated in this educational program . At baseline , 55.56 % of the children had trouble sleeping . When the question naire was administered four months later , only 23.26 % ( p < 0.05 ) had trouble sleeping . Additionally , at baseline , approximately 60–70 % children had some baseline bedtime resistance , anxiety dealing with sleep , issues with sleep duration and /or awakenings in the middle of the night . In the follow up question naire , results showed significant improvements in overall sleep habits , bedtime resistance , sleep anxiety and night awakenings amongst students ( p < 0.05 ) . However , no significant differences were seen in sleep duration and daytime sleepiness . ConclusionS leep deprivation and good sleep habits remain as a pervasive challenge among elementary school students . Administering an animated video about sleep education along with a provider-based education may be an effective tool for educating elementary school students and decreasing the prevalence of these sleep-related issues . Future prospect i ve r and omized studies are suggested PURPOSE The implication s of sleep patterns for adolescent health are well established , but we know less about larger context ual influences on youth sleep . We focused on parents ' workplace experiences as extrafamilial forces that may affect youth sleep . METHODS In a group-r and omized trial focused on employee work groups in the information technology division of a Fortune 500 company , we tested whether a workplace intervention improved sleep latency , duration , night-to-night variability in duration , and quality of sleep of employees ' offspring , aged 9 - 17 years . The intervention was aim ed at promoting employees ' schedule control and supervisor support for personal and family life to decrease employees ' work-family conflict and thereby promote the health of employees , their families , and the work organization . Analyses focused on 93 parent-adolescent dyads ( 57 dyads in the intervention and 46 in the comparison group ) that completed baseline and 12-month follow-up home interviews and a series of telephone diary interviews that were conducted on eight consecutive evenings at each wave . RESULTS Intent-to-treat analyses of the diary interview data revealed main effects of the intervention on youth 's sleep latency , night-to-night variability in sleep duration , and sleep quality , but not sleep duration . CONCLUSIONS The intervention focused on parents ' work conditions , not on their parenting or parent-child relationships , attesting to the role of larger context ual influences on youth sleep and the importance of parents ' work experiences in the health of their children BACKGROUND : Although observational studies have consistently reported an association between media use and child sleep problems , it is unclear whether the relationship is causal or if an intervention targeting healthy media use can improve sleep in preschool-aged children . METHODS : We conducted a r and omized controlled trial of a healthy media use intervention in families of children aged 3 to 5 years . The intervention encouraged families to replace violent or age-inappropriate media content with quality educational and prosocial content , through an initial home visit and follow-up telephone calls over 6 months . Sleep measures were derived from the Child Sleep Habits Question naire and were collected at 6 , 12 , and 18 months after baseline ; repeated- measures regression analyses were used . RESULTS : Among the 565 children analyzed , the most common sleep problem was delayed sleep-onset latency ( 38 % ) . Children in the intervention group had significantly lower odds of “ any sleep problem ” at follow-up in the repeated- measures analysis ( odds ratio = 0.36 ; 95 % confidence interval : 0.16 to 0.83 ) , with a trend toward a decrease in intervention effect over time ( P = .07 ) . Although there was no significant effect modification detected by baseline sleep or behavior problems , gender , or low-income status , there was a trend ( P = .096 ) toward an increased effect among those with high levels of violence exposure at baseline . CONCLUSIONS : The significant effects of a healthy media use intervention on child sleep problems in the context of a r and omized controlled trial suggest that the previously reported relationship between media use and child sleep problems is indeed causal in nature There is considerable research that suggests that school-based social – emotional programs can foster improved mental health and reduce problem behaviors for participating youth ; in contrast , much less is known about the impact of these programs on physical health , even though some of these programs also include at least limited direct attention to promoting physical health behaviors . We examined the effects of one such program , Positive Action ( PA ) , on physical health behaviors and body mass index ( BMI ) , and tested for mediation of program effects through a measure of social – emotional and character development ( SECD ) . Participating schools in the matched-pair , cluster-r and omized trial were 14 low-performing K-8 Chicago Public Schools . We followed a cohort of students in each school from grade s 3 to 8 ( eight waves of data collection ; 1170 total students ) . Student self-reports of health behaviors served as the basis for measures of healthy eating and exercise , unhealthy eating , personal hygiene , consistent bedtime , and SECD . We collected height and weight measurements at endpoint to calculate age- and gender-adjusted BMI z-scores . Longitudinal multilevel modeling analyses revealed evidence of favorable program effects on personal hygiene [ effect size ( ES ) = 0.48 ] , healthy eating and exercise ( ES = 0.21 ) , and unhealthy eating ( ES = −0.19 ) ; in addition , BMI z-scores were lower among students in PA schools at endpoint ( ES = −0.21 ) . Program effects were not moderated by either gender or student mobility . Longitudinal structural equation modeling demonstrated mediation through SECD for healthy eating and exercise , unhealthy eating , and personal hygiene . Findings suggest that a SECD program without a primary focus on health behavior promotion can have a modest impact on outcomes in this domain during the childhood to adolescence transition OBJECTIVE Sleep difficulties are common reasons why parents seek medical intervention in children with autism spectrum disorders ( ASDs ) . We determined whether a pamphlet alone could be used by parents to help their child ’s insomnia . METHODS Thirty-six children with ASD , ages 2 to 10 years , were enrolled . All had prolonged sleep latency confirmed by actigraphy showing a mean sleep latency of 30 minutes or more . Parents were r and omly assigned to receive the sleep education pamphlet or no intervention . Children wore an actigraphy device to record baseline sleep parameters , with the primary outcome variable being change in sleep latency . Actigraphy data were collected a second time 2 weeks after the parent received the r and omization assignment and analyzed by using Student ’s t test . Parents were also asked a series of questions to gather information about the pamphlet and its usefulness . RESULTS Although participants r and omized to the 2 arms did not differ statistically in age , gender , socioeconomic status , total Children ’s Sleep Habits Question naire score , or actigraphy parameters , some differences may be large enough to affect results . Mean change in sleep-onset latency did not differ between the r and omized groups ( pamphlet versus no pamphlet ) . Parents commented that the pamphlet contained good information , but indicated that it would have been more useful to be given specific examples of how to take the information and put it into practice . CONCLUSIONS A sleep education pamphlet did not appear to improve sleep latency in children with ASDs PURPOSE To Output:	Overall , no evidence was found favoring a particular intervention strategy . Conclusion : Due to few high quality studies , evidence for the effectiveness of any particular intervention strategy to stimulate healthy sleep in children is still inconclusive . However , the more effective interventions in stimulating healthy sleep duration and adherence to regular bedtimes were mostly multi-behavioral interventions that included creating daily healthy routines and combined intervention setting s ( e.g. home and school ) .
MS21254	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: About half the patients treated with curative resection for colorectal cancer do not survive long-term . Adjuvant chemotherapy given during and after surgery may prevent hepatic metastases and improve patient survival . In patients with colorectal cancer , we have done a multicentre , r and omised controlled trial comparing five-year survival after intraportal infusion of fluorouracil ( 1 g per day ) plus heparin ( 10,000 U per day ) ( 130 patients ) or heparin alone ( 123 ) during curative resection and for 7 days thereafter , or after resection alone ( 145 ) . There was no reduction in liver metastasis or increased overall survival advantage in either active-treatment arm of the study . However , patients who had stage III , Dukes ' C ( lymph-node-positive ) tumours resected and were treated with fluorouracil plus heparin had a significant ( p less than 0.03 ) survival advantage of about 16 % compared with surgery-only controls . Further study of intraportal infusion of chemotherapeutic agent as adjuvant treatment to surgery in patients with colorectal cancer appears worthwhile In this phase III clinical trial conducted by the Gastrointestinal Tract Cancer Cooperative Group of the European Organization for Research and Treatment of Cancer ( GITCCG-EORTC ) , we evaluated the effect of adjuvant intraportal infusion of heparin ( HEP ) and 5-fluorouracil ( 5-FU ) on overall survival , disease-free survival and time to progression in patients with resectable colon cancer . From January 1983 to June 1987 , 235 patients were r and omised from 14 institutions in seven European countries : 79 patients made up the control group ( control ) : 72 the portal vein infusion group given heparin alone ( 5000 IU daily x 7 consecutive days ) ( HEP ) ; 84 the portal vein infusion group given heparin ( 5000 IU daily x 7 consecutive days ) and 5-FU ( 500 mg/m2 daily x 7 consecutive days ) ( HEP/5-FU ) ; 34 patients were considered ineligible . The 199 patients considered eligible were well balanced for age , sex , Karnofsky index , tumour location , surgery , surgical procedure and Dukes ' stage . Four patients ( 2 control , 1 HEP , 1 HEP/5-FU ) died of surgical complications . No differences were observed between control group and treatment groups ( HEP , HEP/5-FU ) for postoperative complications and number of hospitalisation days . Severe toxicity ( grade 3 - 4 , WHO ) was found in 12 % of patients in the HEP group and 8 % in the HEP/5-FU group . After a median follow-up of 9 years , disease progression was reported in 40 % of patients in the control group , 40 % in the HEP group and 29 % in the HEP/5-FU group . Five-year survival , time to progression and disease-free survival were 69 % , 58 % and 56 % , respectively , in the control arm , 61 % , 58 % and 56 % in the HEP arm , and 71 % , 69 % and 65 % in the HEP/5-FU arm . Based on all r and omised patients , the effect of treatment was not statistically significant with respect to any of the endpoints . It is confirmed that intraportal 5-FU infusion is safe and has a tolerable toxicity , but can not be considered st and ard treatment for patients with resectable colon cancer Background and Methods . Fifty‐one patients with small cell lung cancer ( SCLC ) were treated with alternating urokinase (UK)‐cyclophosphamide‐doxorubicin ( Adriamycin , Adria Laboratories , Columbus , OH)‐vincristine and cisplatin‐etoposide‐vincristine . UK was given as a loading dose of 3000 μg/kg body weight , followed by 3000 μg/kg/h for 6 hours . Thoracic irradiation with split technique ( 46 Gy ) and prophylactic cranial irradiation ( 25 Gy ) were administered to responding patients . A second staging was performed in patients exhibiting a clinical complete response ( CR ) after 1 year Background . A positive influence of anticoagulant treatment in small cell lung cancer ( SCLC ) has been sug gested by experimental and clinical data The Cancer and Leukemia Group B ( CALGB ) conducted a prospect i ve r and omized trial to evaluate the role of warfarin and alternating chemotherapy in extensive small-cell lung cancer ( SCCL ) . After stratification for sex and performance status , patients were r and omly assigned to receive chemotherapy with methotrexate , doxorubicin ( Adriamycin ; Adria Laboratories , Columbus , OH ) , cyclophosphamide , and lomustine ( CCNU ) ( MACC ) , or MACC plus warfarin ( MACC + W ) , or mitomycin , etoposide , cisplatin , and hexamethylmelamine alternating with MACC ( MEPH/MACC ) . Warfarin was given continuously to maintain a prothrombin time of one and one half to twice the control values . A total of 328 patients were enrolled , and 294 were evaluable . There was a statistically significant advantage in objective response rates ( complete [ CR ] and partial responses [ PR ] , respectively ) for MACC + W ( 17 % and 50 % ) as compared with MACC alone ( 8 % and 43 % ) or MEPH/MACC ( 10 % and 38 % ) ( P = .012 ) . Both failure-free survival ( P = .054 Wilcoxon test ) and overall survival ( P = .098 Wilcoxon test ) were higher on MACC + W ( median , 6.6 months and 9.3 months , respectively ) , as compared with MACC ( 5.0 months and 7.9 months ) and MEPH/MACC ( 5.0 months and 7.9 months ) . Toxicity was comparable among the three arms , except for increased hemorrhagic events on MACC + W , which were life-threatening in four patients ( 4 % ) , and lethal in two others ( 2 % ) . These data support the role of warfarin in the treatment of SCCL , but do not establish its mechanism of action . Warfarin deserves further studies in SCCL , particularly in patients with limited disease VA Cooperative Study # 75 was established to test in a controlled , r and omized trial the hypothesis that warfarin anticoagulation would favorably affect the course of certain types of malignancy . No differences in survival were observed between warfarin‐treated and control groups for advanced non‐small cell lung , colorectal , head and neck and prostate cancers . However , warfarin therapy was associated with a significant prolongation in the time to first evidence of disease progression ( P = 0.016 ) and a significant improvement in survival ( P = 0.018 ) for patients with small cell carcinoma of the lung , including the subgroup of patients with disseminated disease at the time of r and omization ( P = 0.013 ) . A trend toward improved survival with warfarin treatment was observed for the few patients admitted to this study with non‐small cell lung cancer who had minimal disease at r and omization . These results suggest that warfarin , as a single anticoagulant agent , may favorably modify the course of some , but not all , types of human malignancy , among which is small cell carcinoma of the lung . Further trials of warfarin may be indicated in patients with limited disease who have cell types that failed to respond when advanced disease was present The object of this study was to see if the addition of anticoagulants to a regimen of cytotoxic drugs would improve the prognosis in patients with small cell carcinoma of the bronchus . Twenty-four patients were r and omly allocated to receive chemotherapy or chemotherapy plus anticoagulants . The median survival in the group receiving the anticoagulants was not improved Analysis of data from a r and omised trial of adjuvant razoxane involving 603 patients with colo-rectal cancer having curative surgery is reported . The results show that razoxane was ineffective but peri-operative subcutaneous heparin treatment apparently conferred a statistically significant improvement in survival at 5 years , or equivalently a reduction in the risk of death . This beneficial effect is apparent in both razoxane treated and control patients and is not explained by demonstrable differences between heparin and non-heparin treated patients in the distribution of known prognostic factors . Adjustment for these factors slightly increased the apparent magnitude of the beneficial effect . RésuméL'analyse des résultats d'une étude r and omisée sur le traitement adjuvant par Razoxane et comprenant 603 patients porteurs d'un cancer colo-rectal ayant eu une chirurgie curatrice est reportée . Les résultats montrent que le Razoxane était inefficient mais que le traitement péri-opératoire par Héparine sous cutanée montrait apparemment une amélioration statistiquement significative dans la survie à 5 ans ou de façon équivalente une réduction du risque de mort . Cet effet bénéfique est apparent dans les deux groupes de patients traités par Razoxane et contrôles et n'est pas expliqué par une différence de la distribution des facteurs pronostiques connus entre les patients héparinés ou non héparinés . L'ajustement de ces facteurs augmente légèrement l'ampleur apparente de cet effet bénéfique In this r and omized trial adjuvant cytotoxic portal vein perfusion in patients undergoing surgery for colorectal cancer without liver metastases was assessed to determine whether the incidence of meta‐chronous liver metastases could be reduced and survival thereby improved . There were 127 control patients and 117 patients who received adjuvant perfusion . A further 13 patients were excluded following r and omization because of cirrhosis in 1 , liver metastases at laparotomy in 3 and technical problems with cannulation in 9 . Dukes ' staging and degree of differentiation were similar in the two groups . There were fewer liver metastases in the perfusion patients and overall survival was improved . However , the benefit appears to be greatest in patients with Dukes ' B colon cancer This prospect ively r and omized clinical trial was carried out in four Dutch hospitals to reduce the development of metachronous liver metastases and to get a better survival in patients with colorectal malignancies after surgically radical en bloc resection of the primary tumor and the regional lymph nodes . Three hundred seventeen patients were r and omized to participate in three trial arms . One group of patients was treated by surgery alone ( control group ) ; in the other patients a catheter was placed in the dilated umbilical vein and advanced until the tip was lying in the left branch of the portal vein . Fifty percent of these patients got immediate postoperative portal infusion with 1 g 5‐fluorouracil ( 5‐FU ) and 5000 U heparin daily for 7 days ; the others received portal vein infusion with urokinase 10,000 U/hour for 24 hours only . Three hundred four patients were eligible . Overall hospital mortality was 3.6 % ( 11 patients ) and was not influenced by adjuvant treatment . After a median follow‐up of 44 months 66 patients have died with relapse and 21 as a result of other causes . The chance of developing liver metastases and other distant metastases after portal infusion with 5‐FU/heparin was one third of the chance in the control group ( P < 0.001 ) . Only an insignificant reduction of the average death rate in the 5‐FU/heparin group was found . In the urokinase group no significant effect in reducing metastases or in survival was noted . Before recommending cytotoxic portal infusion as an adjuvant treatment in patients with colorectal cancer , detailed analysis of other ongoing portal infusion studies has to be awaited and careful calculations have to be made regarding how many patients really can be saved by this treatment Colorectal liver metastases develop by malignant cells entering the portal venous circulation . A r and omized prospect i ve clinical trial was commenced in 1975 to assess the value of adjuvant umbilical vein cytotoxic perfusion ( with 5‐fluorouracil ) following colorectal resection Output:	We conclude that there is no convincing evidence of either positively or negatively effects of UFH on survival of patients with malignancy
MS21255	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Fifty-seven patients developed an episode of catheter-related infection ( CRI ) in the bloodstream during their stay in the intensive care unit ( cases ) and were prospect ively observed to establish the attributable mortality , increase in length of stay , and excess costs . Costs were estimated by multiplying the number of excess days of stay by the reimbursement provided . The outcomes for these cases were compared with those for matched control subjects without CRI . Eight cases were excluded as no control was found . Of the 49 cases , 31 were coagulase-negative staphylococci ( CNS ) . The level of severity was similar for both groups ( APACHE II 15.5 + /- 7 . 2 versus 15.2 + /- 7.3 ) . There were no significant differences ( p > 0 . 20 ) in the mortality observed in the hospital for the cases ( 22.4 % , 95 % confidence interval [ CI ] 0.3 % to 34.9 % ) and the control subjects ( 34.7 % , 95 % CI 21.2 % to 40.1 % ) . Among the survivors , the hospital stay was increased by 19.6 d ( 95 % CI -1.1 ; 40.4 ) . This represents an added cost of 3,124 Euros per episode of CRI among the survivors . In conclusion , our cohort study failed to show a difference in attributable mortality due to CRI in intensive care unit patients . Nevertheless , these infections lead to an increase in hospital stay of approximately 20 d. Each episode of CRI represents an additional cost of more than 3,000 Euros BACKGROUND The use of indwelling central venous catheters ( CVCs ) has become commonplace in the management of children undergoing anticancer treatment . Several types of CVC are available , while information on complications observed in children is scarce . We describe the experience of two tertiary care centers in Italy that prospect ively followed up three types of CVC used at both institutions over a 30-month period . PATIENTS AND METHODS Between January 2000 and May 2002 , double-lumen ( DL ) or single-lumen ( SL ) Hickman-Broviac ( HB ) catheters , and single-lumen pressure-activated safety valve ( PASV ) catheters were used and prospect ively evaluated . Four types of possible complication were defined a priori : mechanical , thrombotic , malfunctioning and infectious . RESULTS Four hundred and eighteen CVCs ( 180 SL-HB , 162 DL-HB and 76 PASV ) were inserted in 368 children , for a total of 107 012 catheter days at risk of complication . At least one complication occurred while using 169 of the devices ( 40 % ) : 46 % of the DL-HB , 46 % of the PASV and 33 % of the SL-HB ( P=0.02 ) catheters . Subjects with hematological malignancies or non-malignant diseases had significantly more complications than those with solid tumors ( P < 0.0001 ) . Overall , 234 complications were documented : 93 infectious [ complication rate per 1000 catheter days at risk (CR)=0.87 ] , 84 malfunctioning ( CR=0.78 ) , 48 mechanical ( CR=0.45 ) and nine thrombotic ( CR=0.08 ) . SL-HB had statistically fewer infectious complications , while PASV had more mechanical complications . In a multivariate regression model , the most significant risk factors for having a CVC complication were hematological disease [ relative risk (RR)=3.0 ; 95 % confidence interval ( CI ) 1.8 - 4.8 ] and age < 6 years at CVC insertion ( RR=2.5 ; 95 % CI 1.5 - 4.1 ) . As for the type of CVC , compared with SL-HB , the DL-HB catheter had a statistically significant two-fold increased risk of any complication ( RR=2.1 ; 95 % CI 1.2 - 3.6 ) , while the PASV catheter had a borderline RR of 1.8 ( 95 % CI 1.0 - 3.6 ) . Analysis by tumor type showed a higher risk of any kind of complication in patients with solid malignancies who had received a DL-HB catheter as compared with an SL-HB catheter ( RR=7.2 ; 95 % CI 2.8 - 18.7 ) . CONCLUSIONS CVCs may cause complications in up to 40 % of patients , with type of CVC , underlying disease and patient age being the three main factors that affect the incidence of CVC-related complications . SL-HB catheters have the best performance Taurolidine has demonstrated inhibition of biofilm formation in vitro . The aim of this study was to compare the effect of catheter locking with taurolidine vs heparin in biofilm formation in central venous catheters . Forty‐eight children with cancer were r and omized to catheter locking by heparin ( n = 22 ) or taurolidine ( n = 26 ) , respectively . After removal , catheters were examined by st and ardized scanning electron microscopy to assess quantitative biofilm formation . Biofilm was present if morphologically typical structures and bacterial cells were identified . Quantitative and semi‐quantitative cultures were also performed . Biofilm was identified in 23 of 26 catheters from the taurolidine group and 21 of 22 catheters from the heparin group . A positive culture was made of six of the catheters locked with taurolidine and heparin , respectively ( p = 0.78 ) . The rate of catheter‐related bloodstream infections ( CRBSI ) was 0.1 per 1000 catheter‐days using taurolidine and 0.9 per 1000 catheter‐days using heparin ( p = 0.03 ) . This r and omized trial confirmed that the use of taurolidine as catheter‐lock compared with heparin reduced the rate of CRBSIs ; this reduction was not related to a reduction in the intraluminal biofilm formation and the rate of bacterial colonization detected by scanning electron microscopy in the two groups HYPOTHESIS Catheter-related bloodstream infection ( CRBSI ) in critically ill surgical patients with prolonged intensive care unit ( ICU ) stays is associated with a significant increase in health care re source use . DESIGN Prospect i ve cohort study . SETTING Surgical ICU at a large tertiary care center . PATIENTS Critically ill surgical patients ( N = 260 ) with projected surgical ICU length of stay greater than 3 days . INTERVENTIONS Central venous catheters were cultured for clinical suspicion of infection . MAIN OUTCOME MEASURES Increases in total hospital cost , ICU cost , hospital days , and ICU days attributable to CRBSI were estimated using multiple linear regression after adjusting for demographic factors and severity of illness ( APACHE III [ Apache Physiology and Chronic Health Evaluation III ] score ) . RESULTS The incidence of CRBSI per 1000 catheter-days was 3.6 episodes ( 95 % confidence interval [ CI ] , 2.1 - 5.8 episodes ) . Microbiologic isolates were Gram-positive bacteria in 75 % , Gram-negative bacteria in 20 % , and yeast in 5 % . After adjusting for demographic factors and severity of disease , CRBSI was associated with an increase of $ 56 167 ( 95 % CI , $ 11 523-$165 735 ; P = .001 ) ( in 1998 dollars ) in total hospital cost , an increase of $ 71 443 ( 95 % CI , $ 11 960-$195 628 ; P<.001 ) in ICU cost , a 22-day increase in hospital length of stay , and a 20-day increase in ICU length of stay . CONCLUSIONS For critically ill surgical patients , CRBSI is associated with a profound increase in re source use . Prevention , early diagnosis , and intervention for CRBSI might result in cost savings in this high-risk population Background Taurolidin/Citrate ( TauroLock ™ ) , a lock solution with broad spectrum antimicrobial activity , may prevent bloodstream infection ( BSI ) due to coagulase-negative staphylococci ( CoNS or ' MRSE ' in case of methicillin-resistant isolates ) in pediatric cancer patients with a long term central venous access device ( CVAD , Port- or/Broviac-/Hickman-catheter type ) . Methods In a single center prospect i ve 48-months cohort study we compared all patients receiving anticancer chemotherapy from April 2003 to March 2005 ( group 1 , heparin lock with 200 IU/ml sterile normal saline 0.9 % ; Canusal ® Wockhardt UK Ltd , Wrexham , Wales ) and all patients from April 2005 to March 2007 ( group 2 ; taurolidine 1.35%/Sodium Citrate 4 % ; TauroLock ™ , Tauropharm , Waldbüttelbrunn , Germany ) . Results In group 1 ( heparin ) , 90 patients had 98 CVAD in use during the surveillance period . 14 of 30 ( 47 % ) BSI were ' primary Gram positive BSI due to CoNS ( n = 4 ) or MRSE ( n = 10 ) ' [ incidence density ( ID ) ; 2.30 per 1000 inpatient CVAD-utilization days].In group 2 ( TauroLock ™ ) , 89 patients had 95 CVAD in use during the surveillance period . 3 of 25 ( 12 % ) BSI were caused by CoNS . ( ID , 0.45 ) . The difference in the ID between the two groups was statistically significant ( P = 0.004 ) . Conclusion The use of Taurolidin/Citrate ( TauroLock ™ ) significantly reduced the number and incidence density of primary catheter-associated BSI due to CoNS and MRSE in pediatric cancer patients Abstract Objective . To prevent catheter occlusion , intermittently used central venous catheters are frequently sealed with vitamin C solution or heparin solution between use . The present study was design ed to test the effectiveness of this approach and to compare the efficiency of sealing solutions . Design and setting . Prospect i ve r and omized study performed on a 9-bed medical ICU and on medical wards of an academic tertiary care center . Participants . Ninety-nine central venous line placements were prospect ively included in the study and r and omized into three treatment groups : sodium chloride 0.9 % , vitamin C ( 200 mg/ml ) and heparin ( 5000 IU/ml ) sealing solutions . Interventions and measurements . Catheters were filled with the respective sealing solution and patency was tested once every 2 days using a st and ardized routine . Catheter patency was compared among the three groups using Kaplan-Meier statistics and log-rank testing . Results . There was a significant difference in catheter patency between the three groups ( p<0.03 , log-rank test ) . A comparison of catheter survival between the catheters filled with heparin and those filled with sodium chloride , but not between those filled with vitamin C solution and with sodium chloride solution , exhibited significant differences in catheter patency ( p<0.04 , log-rank test ) . Conclusions . Local anticoagulation of intermittently used central venous catheters prolongs catheter patency . High-dose ( 5000 IU/ml ) heparin solution is a useful anticoagulant for this purpose , while vitamin C solution does not prolong catheter patency BACKGROUND Bacteremia is a major cause of morbidity in patients using intravascular catheters . Interdialytic locking with antibiotics decreases the incidence of bacteremia , but risks antibiotic resistance . Taurolidine is a nontoxic broad-spectrum antimicrobial agent that has not been associated with resistance . Preliminary evidence suggests that taurolidine-citrate locks decrease bacteremia , but cause flow problems in established catheters . STUDY DESIGN Double-blind r and omized controlled trial . INTERVENTION Interdialytic locking with taurolidine and citrate ( 1.35 % taurolidine and 4 % citrate ) compared with heparin ( 5,000 U/mL ) started at catheter insertion . SETTING & PARTICIPANTS 110 adult hemodialysis patients with tunneled cuffed intravascular catheters inserted at 3 centers in Northwest Engl and . OUTCOMES & MEASUREMENTS Primary end points were time to first bacteremia episode from any cause and time to first use of thrombolytic therapy . RESULTS There were 11 bacteremic episodes in the taurolidine-citrate group and 23 in the heparin group ( 1.4 and 2.4 episodes/1,000 patient-days , respectively ; P = 0.1 ) . There was no significant benefit of taurolidine-citrate versus heparin for time to first bacteremia ( hazard ratio , 0.66 ; 95 % CI , 0.2 - 1.6 : P = 0.4 ) . Taurolidine-citrate was associated with fewer infections caused by Gram-negative organisms than heparin ( 0.2 vs 1.1 infections/1,000 patient-days ; P = 0.02 ) Output:	Conclusions : Catheter locking with TCLS reduced the risk of CRB and Gram-negative bacterial infection .
MS21256	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The current study examined the effects of performance enhancement techniques ( PET 's ) on motor skill performance . Specifically , one hundred fifty college student volunteers ( Men = 41 ; 27.3 % and Women = 109 ; 72.6 % ) were r and omly assigned to one of the nine conditions ( Cond ) : Cond 1 and 2 , simultaneous , externally verbalized self-talk or imagery ( e.g. , participants were instructed to say " aim , back , birdie " or engaged in imagery out loud while putting ) ; Cond 3 and 4 , delayed externally verbalized self-talk or imagery ( e.g. , participants were instructed to say " aim , back , birdie " or engaged in imagery out loud before putting ) ; Cond 5 and 6 , simultaneous , internally verbalized self-talk or imagery ( e.g. , participants were instructed to say " aim , back , birdie " or engaged in imagery silently to oneself while putting ) ; Cond 7 and 8 , delayed internally verbalized ( e.g. , participant were instructed to say " aim , back , birdie " or engaged in imagery silently to oneself before putting ) ; and Cond 9 , no instruction control group . All participants were asked to perform a golf-putting task . Results indicated that participants who implemented several ( PET 's ) increased their putting accuracy across overall difference score evaluations F ( 8 , 141 ) = 4.01 , p < 0.05 when compared to a no instruction control condition . Follow-up analyses indicated that participants who reportedly engaged in ten hours or less of athletic activities per week preferred self-talk strategies F ( 2 , 119 ) = 4.38 , p < 0.05 whereas participants who endorsed ten hours or more of athletic activity per week preferred imagery strategies F ( 2 , 25 ) = 5.27 , p < 0.05 . Key PointsMental imagery and self-talk strategies are implemented by athletes in order to regulate arousal , reduce maladaptive behaviors , reconstruct negative thoughts , and to increase one 's concentration and focus . Results of the current study suggest that participants who engaged in several performance enhancement techniques exhibited enhanced performance on a golf putting task when compared to participants in a control condition . Participants who endorsed limited athletic familiarity and activity ( e.g. , ten hours or less ) preferred self-talk practice whereas participants who endorsed higher ratings scores of athletic familiarity and activity ( e.g. , ten hours or more ) preferred imagery strategies . The results of this study demonstrate the flexibility of Performance Enhancement Techniques ( e.g. , imagery v. self-talk , internal v. external , simultaneous v. delayed ) and how they can be implemented to help an athlete reach his or her full potential In this study , we examined ( 1 ) the relationship between self-talk and affect and ( 2 ) the nature of motivating self-talk . Ninety high-school athletes completed the Affect Grid and the Self-Talk Grid before practice and competition . Significant positive second-order partial correlations of low to moderate strength offered support for a relationship between self-talk and affect . In addition , significant positive second-order partial correlations of moderate strength were found for a relationship between negative-positive self-talk and demotivating-motivating self-talk . An examination of scatter plots indicated that some athletes rated their self-talk as negative as well as being motivational . These findings lend support to the suggestion that negative self-talk may motivate some athletes The effects of instructions to use three different types of thought patterns on the practice performance of superior age-group swimmers were assessed . Two different swimming tasks , two 40 degrees m effort swims and a set of eight 100 m repeats , were used . A balanced design allowed the comparison of the totals of treatment and control ( normal thinking ) conditions . All Ss improved in at least two of the three conditions . All manipulations were significant at the 0.05 level . Group averages indicated that task-relevant content was the most effective condition , followed by mood works , and positive thinking . The importance of using thought content instructions for improving performance was supported by this investigation Abstract This study examined the effects of a cognitive-hypnotic-imagery approach ( CHI ) , cognitive restructuring ( CR ) , and hypnosis only ( HO ) treatments on neuro-muscular performance , muscular growth , reduction of anxiety , and enhancement of self-concept . Thirty-two volunteer male weightlifters served as subjects for the study . Eight subjects were r and omly assigned to each of four treatment conditions conducted over a four-week period . A 4 × 3 factorial design utilizing CANOVA and MANOVA programs was employed . The CHI group showed statistically significant treatment effects over the other groups on all six dependent variables from pretest to post Test I. From post Test I to post Test II , a time period in which no treatment was conducted , self-concept and muscular growth measures for CHI showed significance . The CHI group was statistically superior to all other conditions , ( CR , HO , control ) , which did not significantly differ from each other . Neuro-muscular performance ( supine barbell press mean increase o Output:	Results indicated beneficial effects of positive , instructional , and motivational self-talk for performance . First , negative self-talk did not impede performance . Second , there was inconsistent evidence for the differential effects of instructional and motivational self-talk based on task characteristics . Results from the mediation-based analysis indicate that cognitive and behavioral factors had the most consistent relationships with self-talk .
MS21257	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Multiple studies have shown clear evidence of vitamin D ’s anti-tumor effects on prostate cancer cells in laboratory experiments , but the evidence has not been consistent in humans . We sought to examine the association between vitamin D and prostate cancer risk in a cohort of older men . Methods We conducted a prospect i ve case-cohort study nested within the multicenter Osteoporotic Fractures in Men ( MrOS ) study . Baseline serum 25-OH vitamin D was measured in a r and omly selected sub-cohort of 1,433 men ≥65 years old without a history of prostate cancer and from all participants with an incident diagnosis of prostate cancer ( n = 297 ) . Cox proportional hazards models were used to evaluate the associations between quartiles of total 25-OH vitamin D and incident prostate cancer , as well as Gleason score . Results In comparison with the lowest quartile of 25-OH vitamin D , the hazard ratio for the highest quartile of 25-OH vitamin D was 1.22 ( CI 0.50–1.72 , p = 0.25 ) , no trend across quartiles ( p = 0.94 ) or association with Gleason score was observed . Adjustment for covariates did not alter the results . Conclusions In this prospect i ve cohort of older men , we found no association between serum 25-OH vitamin D levels and subsequent risk of prostate cancer Abstract Background : Calcium , phosphorus , fructose , and animal protein are hypothesized to be associated with prostate cancer risk , potentially via their influence on 1,25-dihydroxyvitamin D3 . We examined these nutrients and overall diet and prostate cancer risk in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study ( ATBC Study ) . Material s and methods : The ATBC Study was a r and omized 2 × 2 trial of alpha-tocopherol and beta-carotene on lung cancer incidence conducted among Finnish male smokers ; 27,062 of the men completed a food-use question naire at baseline , and comprise the current study population . There were 184 incident clinical ( stage 2–4 ) prostate cancer cases diagnosed between 1985 and 1993 . We used Cox proportional hazards models to examine associations between dietary intakes and prostate cancer . Results : We did not observe significant independent associations for calcium and phosphorus and prostate cancer risk . However , men with lower calcium and higher phosphorus intake had a multivariate relative risk of 0.6 ( 95 % CI 0.3–1.0 ) compared to men with lower intakes of both nutrients , adjusting for age , smoking , body mass index , total energy , education , and supplementation group . Of the other foods and nutrients examined , none was significantly associated with risk . Discussion : This study provides , at best , only weak evidence for the hypothesis that calcium and phosphorus are independently associated with prostate cancer risk , but suggests that there may be an interaction between these nutrients This population -based , case-control study in King County , Washington examined associations of energy , fat , vitamin D , and calcium with risk of prostate cancer in 605 incident cases ( ages 40 - 64 years ) identified from the Seattle-Puget Sound Surveillance Epidemiology and End Results registry and 592 controls recruited from the same underlying population using r and om-digit telephone sampling . Self-administered food frequency question naires were used to assess diet over the 3 - 5-year period before diagnosis or interview date . Total energy was associated with increased risk for both local and regional/distant stage disease . The adjusted odds ratios [ 95 % confidence intervals ( CIs ) ] contrasting highest to lowest quintile of energy intake were 2.15 ( 95 % CI , 1.35 - 3.43 ) for local and 1.96 ( 95 % CI , 1.08 - 3.56 ) for regional/distant disease . Fat was associated with regional/distant disease only . Adjusted odds ratios comparing the highest to lowest quintiles of percentage energy from total , saturated , and monounsaturated fats were 2.01 ( 1.03 - 3.92 ) , 1.82 ( 0.93 - 3.56 ) , and 2.00 ( 1.03 - 3.87 ) , respectively . For calcium , adjusted odds ratios contrasting the highest to lowest quartiles were 1.07 ( 0.63 - 1.84 ) for local and 2.12 ( 1.02 - 4.38 ) for regional/distant disease . There were no associations of vitamin D , total polyunsaturated fatty acids , or the highly unsaturated , long-chain eicosapentainoic and docosahexaenoic fatty acids with prostate cancer risk . These results suggest that high energy intake is a risk factor for both localized and nonlocalized prostate cancer , whereas dietary fat and calcium increase the risk of regional/distant disease only . These results are consistent with general dietary guidelines to moderate consumption of total energy and fat , and they motivate further research to consider the potential benefits and risks of high calcium intake A major problem in review ing the published results of different epidemiologic studies of the relation between a quantitative variable and the risk of disease is that the results are presented in many different ways . The purpose of this paper is to exemplify methods by which results expressed either as risks ( or rates ) according to quantlle groups of the quantitative variable or as results derived from a logistic regression analysis can be reexpressed in a uniform manner , as a mean difference in the quantitative variable between the cases of disease and the other subjects in the study . An important assumption of the methods is that the quantitative variable has an approximately normal distribution , and a way of investigating the appropriateness of this assumption is given . The methods can be applied to both prospect i ve and case-control studies and are exemplified by a number of studies of serum albumin concentrations and mortality . In some applications , these methods can be used as a precursor to formal meta- analysis , for example , when differential control of potential confounding factors is not a problem . At the least , the methods can be useful either in quantitatively review ing published studies before undertaking new research or in putting the results of a new study into the context of previously published ones BACKGROUND Dairy intake may increase prostate cancer risk , but whether this is due to calcium 's suppression of circulating vitamin D remains unclear . Findings on calcium and vitamin D intake and prostate cancer are inconsistent . OBJECTIVE We examined the association of dairy , calcium , and vitamin D intake with prostate cancer . DESIGN In a prospect i ve study of 3612 men followed from 1982 - 1984 to 1992 for the first National Health and Nutrition Examination Epidemiologic Follow-up Study , 131 prostate cancer cases were identified . Dietary intake was estimated from question naires completed in 1982 - 1984 . Relative risk ( RR ) and 95 % CIs were estimated by using Cox proportional hazards models adjusted for age , race , and other covariates . RESULTS Compared with men in the lowest tertile for dairy food intake , men in the highest tertile had a relative risk ( RR ) of 2.2 ( 95 % CI : 1.2 , 3.9 ; trend P = 0.05 ) . Low-fat milk was associated with increased risk ( RR = 1.5 ; 95 % CI : 1.1 , 2.2 ; third compared with first tertile ; trend P = 0.02 ) , but whole milk was not ( RR = 0.8 ; 95 % CI : 0.5 , 1.3 ; third compared with first tertile ; trend P = 0.35 ) . Dietary calcium was also strongly associated with increased risk ( RR = 2.2 ; 95 % CI : 1.4 , 3.5 ; third compared with first tertile ; trend P = 0.001 ) . After adjustment for calcium intake , neither vitamin D nor phosphorus was clearly associated with risk . CONCLUSIONS Dairy consumption may increase prostate cancer risk through a calcium-related pathway . Calcium and low-fat milk have been promoted to reduce risk of osteoporosis and colon cancer . Therefore , the mechanisms by which dairy and calcium might increase prostate cancer risk should be clarified and confirmed Abstract Objective : The hormone 1,25-dihydroxyvitamin D ( 1,25(OH)2D ) promotes prostate epithelial cell differentiation in vitro and thus , several groups have hypothesized that men who systemically have lower levels of 1,25(OH)2D may be at increased risk for prostate cancer . To address this hypothesis , we evaluated the association of circulating concentrations of 1,25(OH)2D and its precursor 25-hydroxyvitamin D ( 25(OH)D ) with subsequent risk of prostate cancer . Methods : Prostate cancer cases were 460 men in the Health Professionals Follow-up Study who were diagnosed through 1998 after providing a blood specimen in 1993/95 . 90.2 % of the cases were organ confined or had minimal extraprostatic extension . An equal number of controls who had had a screening PSA test after blood draw were individually matched to cases on age , history of a PSA test before blood draw , and time of day , season , and year of blood draw . Plasma 1,25(OH)2D and 25(OH)D concentrations were determined by radio-immunosorbant assay blindly to case – control status . Odds ratios ( OR ) of prostate cancer and 95 % confidence intervals ( CI ) were estimated from conditional logistic regression models mutually adjusting for quartiles of 1,25(OH)2D and 25(OH)D concentrations and for suspected prostate cancer risk factors . Quartile cutpoints were determined separately by season of blood draw using the distributions among controls . Results : Mean concentrations of 1,25(OH)2D and 25(OH)D were slightly , but not statistically significantly ( p= 0.06 and 0.20 , respectively ) , higher in cases ( 34.3 ± 7.1 pg/ml and 24.6 ± 7.7 ng/ml , respectively ) than in controls ( 33.5 ± 7.1 pg/ml and 23.9 ± 8.2 ng/ml , respectively ) . The OR of prostate cancer comparing men in the top to bottom quartile of 1,25(OH)2D was 1.25 ( 95 % CI : 0.82–1.90 , p-trend = 0.16 ) . For 25(OH)D the OR of prostate cancer comparing the top and bottom quartiles was 1.19 ( 95 % CI : 0.79–1.79 , p-trend = 0.59 ) . These findings did not vary by level of the other metabolite , age at diagnosis , family history of prostate cancer , or factors that are thought to influence 25(OH)D levels . Conclusion : In this prospect i ve study , we did not observe an inverse association between plasma concentrations of 1,25(OH)2D or 25(OH)D and incident prostate cancer , although we can not rule out potential effects at later stages of the disease Intake of calcium and /or dairy products has been associated with increased risk of prostate cancer in some epidemiological studies . One potential biological mechanism is that high calcium intake down-regulates 1,25 dihydroxy vitamin D(3 ) , which may increase cell proliferation in the prostate . We examined the association between calcium , dairy intake , and prostate cancer incidence in the Cancer Prevention Study II Nutrition Cohort , a prospect i ve cohort of elderly United States adults . Participants in the study completed a detailed question naire on diet , medical history , and lifestyle at enrollment in 1992 - 1993 . After excluding men with a history of cancer or incomplete dietary information , 65,321 men remained for analysis . During follow-up through August 31 , 1999 , we documented 3811 cases of incident prostate cancer . Multivariate-adjusted rate ratios ( RRs ) were calculated using Cox proportional hazards models . Total calcium intake ( from diet and supplements ) was associated with modestly increased risk of prostate cancer [ RR = 1.2 , 95 % confidence interval ( CI ) = 1.0 - 1.6 for > or=2000 versus < 700 mg/day , P trend = 0.02 ) . High dietary calcium intake ( > or=2000 versus < 700 mg/day ) was also associated with increased risk of prostate cancer ( RR = 1.6 , 95 % CI = 1.1 - 2.3 , P trend = 0.10 ) , although moderate levels of dietary calcium were not associated with increased risk . Dairy intake was not associated with prostate cancer risk . The association between prostate cancer and total calcium intake was strongest for men who reported not having prostate-specific antigen testing before 1992 ( RR = 1.5 , 95 % CI = 1.1 - 2.0 , P trend < 0.01 for > or= 2000 mg/day of total calcium ; RR = 2.1 , 95 % CI = 1.3 - 3.4 > or=2000 mg/day of dietary calcium , P trend = 0.04 ) . Our results support the hypothesis that very high calcium intake , above the recommended intake for men , may modestly increase risk of prostate cancer PURPOSE Substantial experimental and epidemiological data indicate that 1,25-dihydroxyvitamin D3 ( calcitriol ) has potent antiproliferative effects on human prostate cancer cells . Output:	Conclusion Published literature provides little evidence to support a major role of vitamin D in preventing prostate cancer or its progression
MS21258	*TASK* the task is to summarize an input biomedical literature in six sentences *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 : Mobile-bearing ankle replacements have become popular outside of the United States over the past two decades . The goal of the present study was to perform a prospect i ve evaluation of the safety and efficacy of a mobile-bearing prosthesis to treat end stage ankle arthritis . We report the results of three separate cohorts of patients : a group of Sc and anavian Total Ankle Replacement ( STAR ) patients and a control group of ankle fusion patients ( the Pivotal Study Groups ) and another group of STAR total ankle patients ( Continued Access Group ) whose surgery was performed following the completion of enrollment in the Pivotal Study . Material s and Methods : The Pivotal Study design was a non-inferiority study using ankle fusion as the control . A non-r and omized multi-centered design with concurrent fusion controls was used . We report the initial perioperative findings up to 24 months following surgery . For an individual patient to be considered an overall success , all of the following criteria needed to be met : a ) a 40-point improvement in total Buechel-Pappas ankle score , b ) no device failures , revisions , or removals , c ) radiographic success , and d ) no major complications . In the Pivotal Study ( 9/00 to 12/01 ) , 158 ankle replacement and 66 arthrodesis procedures were performed ; in the Continued Access Study ( 4/02 to 10/06 ) , 448 ankle replacements were performed , of which 416 were at minimum 24 months post-surgery at time of the data base closure . Results : Major complications and need for secondary surgical intervention were more common in the Pivotal Study arthroplasty group than the Pivotal Study ankle fusion group . In the Continued Access Group , secondary procedures performed on these arthroplasty patients decreased by half when compared with the Pivotal Arthroplasty Group . When the Pivotal Groups were compared , treatment efficacy was higher for the ankle replacement group due to improvement in functional scores . Pain relief was equivalent between fusion and replacement patients . The hypothesis of non-inferiority of ankle replacement was met for overall patient success . Conclusion : By 24 months , ankles treated with STAR ankle replacement ( in both the Pivotal and Continued Access Groups ) had better function and equivalent pain relief as ankles treated with fusion . Level of Evidence : II , Prospect i ve Controlled Comparative Surgical We describe the medium-term results of a prospect i ve study of 200 total ankle replacements at a single-centre using the Sc and inavian Total Ankle Replacement . A total of 24 ankles ( 12 % ) have been revised , 20 by fusion and four by further replacement and 27 patients ( 33 ankles ) have died . All the surviving patients were seen at a minimum of five years after operation . The five-year survival was 93.3 % ( 95 % confidence interval ( CI ) 89.8 to 96.8 ) and the ten-year survival 80.3 % ( 95 % CI 71.0 to 89.6 ) . Anterior subluxation of the talus , often seen on the lateral radiograph in osteoarthritic ankles , was corrected and , in most instances , the anatomical alignment was restored by total ankle replacement . The orientation of the tibial component , as seen on the lateral radiograph , also affects the position of the talus and if not correct can hold the talus in an abnormal anterior position . Subtalar arthritis may continue to progress after total ankle replacement . Our results are similar to those published previously We describe the results of a r and omised , prospect i ve study of 200 ankle replacements carried out between March 2000 and July 2003 at a single centre to compare the Buechel-Pappas ( BP ) and the Sc and inavian Total Ankle Replacement ( STAR ) implant with a minimum follow-up of 36 months . The two prostheses were similar in design consisting of three components with a meniscal polyethylene bearing which was highly congruent on its planar tibial surface and on its curved talar surface . However , the design s were markedly different with respect to the geometry of the articular surface of the talus and its overall shape . A total of 16 ankles ( 18 % ) was revised , of which 12 were from the BP group and four of the STAR group . The six-year survivorship of the BP design was 79 % ( 95 % confidence interval ( CI ) 63.4 to 88.5 and of the STAR 95 % ( 95 % CI 87.2 to 98.1 ) . The difference did not reach statistical significance ( p = 0.09 ) . However , varus or valgus deformity before surgery did have a significant effect ) ( p = 0.02 ) on survivorship in both groups , with the likelihood of revision being directly proportional to the size of the angular deformity . Our findings support previous studies which suggested that total ankle replacement should be undertaken with extreme caution in the presence of marked varus or valgus deformity The purpose of the current prospect i ve study was to determine the midterm results of 68 total ankle replacements with the Sc and inavian Total Ankle Replacement ( S.T.A.R. ) prosthesis . The 65 patients ( 34 women and 31 men ; mean age at surgery , 56.1 years [ range , 22 - 85 years ] ) were assessed clinical ly and radiologically after 3.7 years ( range , 2.4 - 6.2 years ) . Thirty-five patients ( 54 % ) were totally pain-free . The overall clinical score was grade d as excellent or good in 67 ankles . The American Orthopaedic Foot and Ankle Society hindfoot score improved from 24.7 points ( range , 3 - 44 points ) preoperatively to 84.3 points ( range , 44 - 100 points ) at followup . Three patients ( three ankles , 4.4 % ) had a ballooning bone lysis on the tibial side . Despite prophylaxis , periarticular hypertrophic bone formation was seen in 43 ankles ( 63 % ; 42 patients ) , associated with a decrease of dorsiflexion and plantar flexion . Nine ankles ( 13 % ; nine patients ) had revision surgery because of problems with the components and 14 ankles ( 21 % ; 14 patients ) had secondary or additional operations . All revision or secondary surgeries were successful , and no ankle had to be converted to an ankle arthrodesis . The early experience with the S.T.A.R. ankle implant is encouraging , although we have encountered more complications and potential problems than previously reported Early design s of Total Ankle Replacement ( TAR ) had a high failure rate . More recent experience with the 3-piece , meniscal bearing , total ankle replacement has been more promising . We report a review of the early results of our first 22 prostheses in 20 patients undergoing Sc and inavian Total Ankle Replacement ( STAR ) in Northern Irel and . There was a mean follow-up time of 26 months . Seventeen patients are pain-free at the ankle joint during normal daily activities . Two of the early cases have required revision surgery due to technical errors . Other complications have included malleolar fractures , poor wound healing and postoperative stiffness . These early results show high levels of patient satisfaction , and we are encouraged to continue with total ankle arthroplasty . There is a steep initial learning curve and use of TAR should be restricted to foot and ankle surgeons . ImagesFig 1Figs 2a and bFigs 2 c and Fifty-eight patients with either rheumatoid arthritis or osteoarthritis were treated with meniscal-bearing ankle prostheses . The concept was to mobilize , align , and stabilize the ankle before resurfacing it . Cement was used for prostheses fixation in 33 patients ( 1986 - 1989 ) and 25 patients had fixation without cement ( 1990 - 1995 ) . All patients in one prospect i ve series were followed up yearly with radiographs and with a clinical scoring system giving a maximum of 100 points . This allowed for a patient-controlled prospect i ve study . No patients were lost to followup . The only detectable difference in the treatment was the fixation mode . For the purpose of comparing patients with cemented and uncemented prostheses , the patients who had surgery between 1986 and 1989 were not followed up after 1997 , and patients who had surgery between 1990 and 1995 were not followed up after 2002 . The mean followup was 9.4 years . Failure was defined as prosthesis revision or change to arthrodesis for any reason . In the cemented group , nine of 33 patients had revision surgery or fusion . In the uncemented group , one of 25 patients had revision surgery . Survivorship analysis for 12 years based on life tables showed a 70 % survival rate ( confidence limit , 60.3 - 78.5 ) for the cemented group and 95.4 % survival rate ( confidence limit , 91.0 - 99.9 ) for the uncemented group . The average clinical scores at the latest followup were 74.2 + /- 19.3 for the cemented group and 91.9 + /- 7.4 points for the uncemented group . Therefore , unconstrained meniscal-bearing ankle prostheses should be uncemented The purpose of this study was to evaluate the function of the ankle joint during walking before and after Sc and inavian Total Ankle Replacement ( STAR ) . Nine patients ( six males and three females ) with an average age of 65 years , scheduled for unilateral total ankle replacement for osteoarthritis and rheumatoid arthritis , were evaluated both preoperatively and postoperatively in a gait analysis laboratory . Arthroplasty patients showed reduced range of motion at the ankle compared to normal controls . Postoperative arthroplasty subjects had significantly improved external ankle dorsiflexion moment , the moment that affects the plantarflexor muscles , when compared to their preoperative status . The moment in arthroplasty patients was increased , indicating improved function of the ankle joint One hundred consecutive cases treated with ankle arthroplasty for osteoarthritis ( OA ) or rheumatoid arthritis were followed prospect ively and annually for up to 15 years . Survivorship analysis was performed , with the endpoint being prosthesis revision or change to arthrodesis . Patients who were younger than 50 years at the first implantation constituted one group ( group A , 30 ankles ) . The other group ( group B , 70 ankles ) consisted of patients aged 50 years or older at the first implantation . All patients were assessed clinical ly according to the Kofoed Ankle Score . The distribution of OA/rheumatoid arthritis in group A was 18/12 , and in group B it was 43/27 ( not significant ) . The median age in group A was 46 years ( range , 22–49 years ) , and in group B it was 63 years ( range , 51–83 years ) . In group A , one case was revised , and three cases were converted to arthrodesis after a median of 5 years ( range , 5–9 years ) . In group B , four cases were revised , and four cases were converted to arthrodesis after a median of 5.5 years ( range , 2–8 years ) . The results of cases with traumatic OA did not differ between groups A and B. It was concluded that the results of ankle arthroplasty were of equal quality in patients younger than 50 years and those who were older An up to 12-year follow-up of 51 single-coated STAR revealed that 15 ankles had undergone fusion . The mean time from primary surgery to the first revision was median 51 months . In a series of 58 double-coated STAR ankles followed up to 5 years only one ankle had to be revised for component loosening . In this series the clinical survival rate was 98 % and the radiographic survival rate 94 % at 5 years . The radiographic survival rate , with component loosening as endpoint , was significantly better for the last 31 cases in the series of the single-coated prostheses . However , the loosening rate did not differ when these latter 31 cases were compared with the cases operated on with a double-coated prosthesis . One may conclude that improvement of the anchoring surfaces has had a limited influence on the radiographic survival of the STAR ankle . However , from the clinical survivorship figures it is obvious that the learning process continues as the difference in revision rate between the 31 last implanted single-coated and the later on implanted double-coated prostheses approached significance Output:	Conclusions We found that STAR prosthesis achieved encouraging results in terms of intermediate to long-term outcome . The major reasons for implant failure were aseptic loosening and malalignment . Maybe the increase of surgeons ’ experience and patient selection could improve outcomes and decrease failure rate
MS21259	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: STUDY OBJECTIVE We conducted a prospect i ve , r and omized , controlled trial to test the hypothesis that a 34-minute video self-instruction ( VSI ) training program for adult CPR would yield comparable or better CPR performance than the current community st and ard , the American Heart Association Heartsaver course . METHODS Incoming freshman medical students were r and omly assigned to VSI or the Heartsaver CPR course . Two to 6 months after training , we tested subjects to determine their ability to perform CPR in a simulated cardiac arrest setting . Blinded observers used explicit criteria to assess our primary outcome , CPR performance skill . In addition , we assessed secondary outcomes including sequential performance of individual skills , ventilation and chest compression characteristics , and written tests of CPR-related knowledge and attitudes . RESULTS VSI trainees displayed superior overall performance compared with traditional trainees . Twenty of 47 traditional trainees ( 43 % ) were judged not competent in their performance of CPR , compared with only 8 of 42 VSI trainees ( 19 % ; absolute difference , 24 % ; 95 % confidence interval , 5 % to 42 % ) . CONCLUSION In a group of incoming freshman medical students , we found that a half-hour of VSI result ed in superior overall CPR performance compared with that in traditional trainees . If vali date d by further research , VSI may provide a simple , quick , and inexpensive alternative to traditional CPR instruction for health care workers and , perhaps , the general population STUDY OBJECTIVE Despite the proven efficacy of cardiopulmonary resuscitation ( CPR ) , only a small fraction of the population knows how to perform it . As a result , rates of byst and er CPR and rates of survival from cardiac arrest are low . Byst and er CPR is particularly uncommon in the African American community . Successful development of a simplified approach to CPR training could boost rates of byst and er CPR and save lives . We conducted the following r and omized , controlled study to determine whether video self-instruction ( VSI ) in CPR results in comparable or better performance than traditional CPR training . METHODS This r and omized , controlled trial was conducted among congregational volunteers in an African American church in Atlanta , GA . Subjects were r and omly assigned to receive either 34 minutes of VSI or the 4-hour American Heart Association " Heartsaver " CPR course . Two months after training , blinded observers used explicit criteria to assess CPR performance in a simulated cardiac arrest setting . A recording manikin was used to measure ventilation and chest compression characteristics . Participants also completed a written test of CPR-related knowledge and attitudes . RESULTS VSI trainees displayed a comparable level of performance to that achieved by traditional trainees . Observers scored 40 % of VSI trainees competent or better in performing CPR , compared with only 16 % of traditional trainees ( absolute difference 24 % , 95 % confidence interval 8 % to 40 % ) . Data from the recording manikin confirmed these observations . VSI trainees and traditional trainees achieved comparable scores on tests of CPR-related knowledge and attitudes . CONCLUSION Thirty-four minutes of VSI can produce CPR of comparable quality to that achieved by traditional training methods . VSI provides a simple , quick , consistent , and inexpensive alternative to traditional CPR instruction , and may be used to extend CPR training to historically underserved population BACKGROUND Byst and er CPR improves outcomes after out of hospital cardiac arrest . The length of current 4-h classes in cardiopulmonary resuscitation ( CPR ) is a barrier to more widespread dissemination of CPR training and older adults in particular are underrepresented in traditional classes . Training with a brief video self-instruction ( VSI ) program has shown that this type of training can produce short-term skill performance at least as good as that seen with traditional American Heart Association ( AHA ) Heartsaver training , although it is unclear whether there is comparable skill retention . METHODS AND RESULTS Two hundred and eight-five adults between the ages of 40 and 70 who had no CPR training within the past 5 years were assigned at r and om to a no-training control group , Heartsaver ( HS ) training , or one of three versions of brief VSI ( i.e. , self-trained-ST subjects ) . Post-training performance of CPR skills was assessed in a scenario format by human examiners and by sensored manikin at Time 1 ( immediately post-training ) and again at Time 2 ( 2 months post-training ) . Performance by controls was assessed only once . Significant ( P<.001 ) decline was observed in the three measures recorded by examiners ; assess responsiveness ( from 72 % to 60 % for HS subjects and from 90 % to 77 % for ST subjects ) , call 911 ( from 82 % to 74 % for HS subjects and from 71 % to 53 % for ST subjects ) , and overall performance ( from 42 % to 30 % for HS subjects and from 60 % to 44 % for ST subjects ) . Significant ( P<.001 ) decline was observed in two of three skills measured by a sensored manikin : ventilation volume ( from 40 % to 36 % for HS subjects and from 61 % to 41 % for ST subjects , with a significant [ P=.028 ] interaction ) and correct h and placement ( from 68 % to 59 % for HS subjects and from 80 % to 64 % for ST subjects ) . Heartsaver and self-trained subjects generally showed similar rates of decline . At Time 2 , examiners rated trained subjects better than untrained controls in all skills except calling 911 , where self-trained subjects did not differ from controls ; manikin data revealed that trained subjects ' performance was better than that of controls for ventilation volume , but had declined to the level of controls for both h and placement and compression depth . CONCLUSIONS Adults between 40 and 70 years of age who participated in a CPR VSI program experienced performance decline in their CPR skills after a post-training interval of 2 months . However , this decline was no greater than that seen in subjects who took Heartsaver training . The VSI program produced retention performance at least as good as that seen with traditional training . Additional effort is needed to improve both initial performance and retention of CPR skills . CONDENSED ABSTRACT Retention of CPR skills was compared 2 months post-training for adults between 40 and 70 years old who had taken either a traditional Heartsaver CPR course or a 22-min video self-directed training course . Although performance declines occurred in the 2-month interval , self-trained subjects generally demonstrated CPR skill retention equivalent to that of Heartsaver-trained subjects , although for both groups skill decline on some measures reached the level of untrained controls OBJECTIVES / PURPOSE To test registered nurses ' abilities to retain basic or advanced life support psychomotor skills and theoretical knowledge . DESIGN A repeated- measures , quasi-experimental design was used . METHODS Written and performance tests ( initial , post-training , and final testing ) used scenarios requiring performance of advanced cardiac life support ( ACLS ) or basic life support ( BLS ) skills . Final testing was by r and om assignment to 3 , 6 , 9 , or 12 months . SAMPLE A convenience sample ( n=133 ) was used . INSTRUMENTATION American Heart Association 2000 ACLS and BLS evaluation tools were used in a simulated testing environment . FINDINGS Findings show nurses retain theoretical knowledge but performance skills de grade quickly . ACLS skills de grade faster than BLS skills with 63 % passing BLS at 3 months and 58 % at 12 months . Only 30 % of participants passed ACLS skills at 3 months and 14 % at 12 months . These findings are similar to the results of other investigators in over a decade of research . CONCLUSIONS Study results showed a decline in skills retention with nurses unable to perform ACLS and BLS skills to st and ard for the entire certification period . The need for more frequent refresher training is needed . No formal research at this institution indicates skill degradation adversely affected patient outcomes . Further research on ACLS and BLS course content , design , management , and execution is needed INTRODUCTION The optimal strategy to retrain basic life support ( BLS ) skills on a manikin is unknown . We analysed the differential impact of a video ( video group , VG ) , voice feedback ( VFG ) , or a serial combination of both ( combined group , CG ) on BLS skills in a self-learning ( SL ) environment . METHODS Two hundred and thirteen medicine students were r and omly assigned to a VG , a VFG and a CG . The VG refreshed the skills with a practice -while-watching video ( abbreviated Mini Anne ™ video , Laerdal , Norway ) and a manikin , the VFG with a computer-guided manikin ( Resusci Anne Skills Station ™ , Laerdal , Norway ) and the CG with a serial combination of both . Each student performed two sequences of 60 compressions , 12 ventilations and three complete cycles of BLS ( 30:2 ) . The proportions of students achieving adequate skills were analysed using generalised estimating equations analysis , taking into account pre-test results and training strategy . RESULTS Complete data sets were obtained from 192 students ( 60 VG , 69 VFG and 63 CG ) . Before and after training , ≥70 % of compressions with depth ≥50 mm were achieved by 14/60 ( 23 % ) vs. 16/60 ( 27 % ) VG , 24/69 ( 35 % ) vs. 50/69 ( 73 % ) VFG and 19/63 ( 30 % ) vs. 41/63 ( 65 % ) CG ( P<0.001 ) . Compression rate 100 - 120/min was present in 27/60 ( 45 % ) vs. 52/60 ( 87 % ) VG , 28/69 ( 41 % ) vs. 44/69 ( 64 % ) VFG and 27/63 ( 43 % ) vs. 42/63 ( 67 % ) CG ( P=0.05 ) . Achievement of ≥70 % ventilations with a volume 400 - 1000 ml was present in 29/60 ( 49 % ) vs. 32/60 ( 53 % ) VG , 32/69 ( 46 % ) vs. 52/69 ( 75 % ) VFG and 25/63 ( 40 % ) vs. 51/63 ( 81 % ) CG ( P=0.001 ) . There was no between-groups difference for complete release . CONCLUSIONS Voice feedback and a sequential combination of video and voice feedback are both effective strategies to refresh BLS skills in a SL station . Video training alone only improved compression rate . None of the three strategies result ed in an improvement of complete release AIM To evaluate the retention of skills 6 months after training in ventilation and chest compressions ( CPR ) on a manikin with computer based on-line voice advisory feedback and the possible effects of initial overtraining . METHODS Thirty five volunteers had 20 min provisional CPR training on a manikin with computer based voice advisory feedback but without an instructor . The appropriate feedback was taken from a pre-recorded list depending on performance measured by the manikin -- computer system versus set limits for ventilation and compression variables . One group in addition was r and omised to receive 10 similar 3 min training sessions during 1 week in the following month ( overtrained group ) . All ventilation and compression variables were measured without feedback before and after the initial training session , with feedback immediately thereafter , and both without and with feedback 6 months after the initial training session . RESULTS The initial training improved all variables . Compressions with correct depth increased from a mean of 33 to 77 % , and correct inflations from a mean of 9 to 58 % . After 6 months , the results for the controls were not significantly different from pre-training , except for a higher of correct inflations ( 18 % ) , while the overtrained group had better retention of skills including the correct compression depth ( mean 61 % ) and inflations ( mean 42 % ) . When verbal feedback was added both the compressions and ventilations immediately improved both when tested immediately and 6 months after the initial training session . CONCLUSIONS The computer-based voice advisory manikin ( VAM ) feedback system can improve immediate performance of basic life support ( BLS ) skills , with better long-term retention with overtraining BACKGROUND Each year , more than 1.5 million health care professionals receive advanced life support ( ALS ) training . OBJECTIVE To determine whether a blended approach to ALS training that includes electronic learning ( e-learning ) produces outcomes similar to those of conventional , instructor-led ALS training . DESIGN Open-label , noninferiority , r and omized trial . R and omization , stratified by site , was generated by Sealed Envelope ( Sealed Envelope , London , United Kingdom ) . ( International St and ardized R and omized Controlled Trial Number Register : ISCRTN86380392 ) SETTING 31 ALS centers in the United Kingdom and Australia . PARTICIPANTS 3732 health care professionals recruited between December 2008 and October 2010 . INTERVENTION A 1-day course supplemented with e-learning versus a conventional 2-day course . MEASUREMENTS The primary outcome was performance in a cardiac arrest simulation test at the end of the course . Secondary outcomes comprised knowledge- and skill-based assessment s , repeated assessment after remediation training , and re source use . RESULTS 440 of the 1843 participants r and omly assigned to the blended course and 444 of the 1889 participants r and omly assigned to conventional training did not attend the courses . Performance in the cardiac arrest simulation test after course attendance was lower in the electronic advanced life support ( e-ALS ) group compared with the conventional advanced life support ( c-ALS ) Output:	With the increasing pressure of re sources and time , tradiional instructor led courses may not be the most efficient method or delivering resuscitation training to sharp end CPR providers . The automated voice feedback/prompt ystem used a computer-guided manikin with automated
MS21260	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Reflexology is an ancient , mild and non-invasive technique , used widely as one of the non-pharmacological methods for pain relief . The aim of this research was to determine the effect of reflexology on pain intensity as well as to determine the duration of labor in primiparas . Methods In 2008 , a r and omized clinical trial study was conducted r and omly enrolling 120 parturient women with low risk pregnancy into three groups in Shahid Akbarabadi Hospital , Tehran , Iran . The first group received 40 minutes of reflexology at the beginning of active phase ( 4 - 5 cm cervical dilatation ) . Emotional support was offered for the second group in the same stage of pregnancy and with the same duration . The third group received only routine care during labor . Pain severity was evaluated with visual analogue scale ( 0 to 10 cm ) . In all groups , pregnant women were asked to evaluate the severity of pain experienced before and after intervention and also at cervical dilatations of 6 - 7 cm and 8 - 10 cm respectively . Data were collected through the numerical pain scale . Results Pain intensity at all the three stages of cervical dilatation was significantly lower in the reflexology group . During the 4 - 5 cm dilatation stage , women in the supported group reported less severe pain compared to those receiving routine care , but no significant differences at the later stages of labor . This indicates that reflexology could decrease the duration of first , second and third stages of labor . Conclusion Our findings showed that reflexology can be useful to decrease the pain intensity as well as duration of labor CONTEXT A prior national survey documented the high prevalence and costs of alternative medicine use in the United States in 1990 . OBJECTIVE To document trends in alternative medicine use in the United States between 1990 and 1997 . DESIGN Nationally representative r and om household telephone surveys using comparable key questions were conducted in 1991 and 1997 measuring utilization in 1990 and 1997 , respectively . PARTICIPANTS A total of 1539 adults in 1991 and 2055 in 1997 . MAIN OUTCOMES MEASURES Prevalence , estimated costs , and disclosure of alternative therapies to physicians . RESULTS Use of at least 1 of 16 alternative therapies during the previous year increased from 33.8 % in 1990 to 42.1 % in 1997 ( P < or = .001 ) . The therapies increasing the most included herbal medicine , massage , megavitamins , self-help groups , folk remedies , energy healing , and homeopathy . The probability of users visiting an alternative medicine practitioner increased from 36.3 % to 46.3 % ( P = .002 ) . In both surveys alternative therapies were used most frequently for chronic conditions , including back problems , anxiety , depression , and headaches . There was no significant change in disclosure rates between the 2 survey years ; 39.8 % of alternative therapies were disclosed to physicians in 1990 vs 38.5 % in 1997 . The percentage of users paying entirely out-of-pocket for services provided by alternative medicine practitioners did not change significantly between 1990 ( 64.0 % ) and 1997 ( 58.3 % ) ( P=.36 ) . Extrapolations to the US population suggest a 47.3 % increase in total visits to alternative medicine practitioners , from 427 million in 1990 to 629 million in 1997 , thereby exceeding total visits to all US primary care physicians . An estimated 15 million adults in 1997 took prescription medications concurrently with herbal remedies and /or high-dose vitamins ( 18.4 % of all prescription users ) . Estimated expenditures for alternative medicine professional services increased 45.2 % between 1990 and 1997 and were conservatively estimated at $ 21.2 billion in 1997 , with at least $ 12.2 billion paid out-of-pocket . This exceeds the 1997 out-of-pocket expenditures for all US hospitalizations . Total 1997 out-of-pocket expenditures relating to alternative therapies were conservatively estimated at $ 27.0 billion , which is comparable with the projected 1997 out-of-pocket expenditures for all US physician services . CONCLUSIONS Alternative medicine use and expenditures increased substantially between 1990 and 1997 , attributable primarily to an increase in the proportion of the population seeking alternative therapies , rather than increased visits per patient The objectives of this study is to examine the effects of neuromuscular therapy ( NMT ) on motor and nonmotor symptoms in Parkinson 's disease ( PD ) . Thirty-six subjects with PD were r and omly assigned to NMT or music relaxation ( MR , or active control ) . Subjects received treatment twice a week for 4 weeks . Testing was conducted at baseline , after final treatment , and 8 days after final treatment . Primary outcome measures were the Motor subscale of the United Parkinson Disease Rating Scale ( UPDRS ) and the Clinical Global Impression scale ( CGI-Change ) . Secondary outcome measures included a PD-specific quality of life scale ( PDQ-39 ) , quantitative measures of motor function , and severity scales for anxiety and depression symptoms . NMT result ed in a significant and sustained improvement in the Motor subscale of the UPDRS ( P < or = 0.0001 ) , most notable in the tremor scores . Also improved 1 week after the last treatment were the CGI scores ( P = 0.007 ) and the finger-tapping speed ( P = 0.001 ) . The MR active control group had a slight improvement in tremor but evidence d no other change in motor function . Both groups exhibited a modest improvement in quality of life immediately after the last treatment . This effect was sustained for 8 days only in the MR group . In the nonmotor domains , the MR group evidence d improvements in mood ( P = 0.001 ) and anxiety ( P = 0.002 ) , whereas NMT had no effect on mood ( P = 0.09 ) , and its initial effect on anxiety ( P = 0.0009 ) dissipated after 8 days ( P = 0.40 ) . Group differences for UPDRS motor score and patient CGI-Change were superior in the NMT compared to the MR group . There was no group difference in PDQ-39 scores or in nonmotor measures . The findings suggest that NMT can improve motor and selected nonmotor symptoms in PD and that this effect is more durable for the motor symptoms . The results of this pilot study warrant larger controlled studies to examine dose range , durability , and mechanisms of NMT in PD function Purpose To investigate the effects of massage and presenting an attendant on pain , anxiety and satisfaction during labor to clarify some aspects of using an alternative complementary strategy . Methods 120 primiparous women with term pregnancy were divided into massage , attendant and control groups r and omly . Massage group received firm and rhythmic massage during labor in three phases . After 30 min massage at each stage , pain , anxiety and satisfaction levels were evaluated . Self-reported present pain intensity scale was used to measure the labor pain . Anxiety and satisfaction were measured with the st and ard visual analog scale . Results Massage group had lower pain state in second and third phases ( p < 0.05 ) in comparison with attendant group but reversely , the level of anxiety was lower in attendant group in second and third phases ( p < 0.05 ) and satisfaction was higher in massage group in all four phases ( p < 0.001 ) . The massage group had lower pain and anxiety state in three phases in comparison with control group ( p < 0.05 ) . Data analysis of satisfaction level showed higher values in four phases in massage group compared with control ( p < 0.001 ) and comparison of attendant and control groups showed higher satisfaction in attendant group in phases 2 , 3 and 4 as well ( p < 0.001 ) . Duration of active phase was lower in massage group ( p < 0.001 ) . Conclusions Findings suggest that massage is an effective alternative intervention , decreasing pain and anxiety during labor and increasing the level of satisfaction . Also , the supportive role of presenting an attendant can positively influence the level of anxiety and satisfaction QUESTION Does massage relieve pain in the active phase of labour ? DESIGN R and omised trial with concealed allocation , assessor blinding for some outcomes , and intention-to-treat analysis . PARTICIPANTS 46 women pregnant at ≥ 37 weeks gestation with a single fetus , with spontaneous onset of labour , 4 - 5 cm of cervical dilation , intact ovular membranes , and no use of medication after admission to hospital . INTERVENTION Experimental group participants received a 30-min lumbar massage by a physiotherapist during the active phase of labour . A physiotherapist attended control group participants for the same period but only answered questions . Both groups received routine perinatal care . OUTCOME MEASURES The primary outcome was pain severity measured on a 100 mm visual analogue scale . Secondary outcomes included the Short Form McGill Pain Question naire , pain location , and time to analgesic medication use . After labour , a blinded research er also recorded duration of labour , route of delivery , neonatal outcomes , and the participant 's satisfaction with the physiotherapist during labour . RESULTS At the end of the intervention , pain severity was 52 mm ( SD 20 ) in the experimental group and 72 mm ( SD 15 ) in control group , which was significantly different with a mean difference of 20 mm ( 95 % CI 10 to 31 ) . The groups did not differ significantly on the other pain-related outcome measures . Obstetric outcomes were also similar between the groups except the duration of labour , which was 6.8hr ( SD 1.6 ) in the experimental group and 5.7hr ( SD 1.5 ) in the control group , mean difference 1.1hr ( 95 % CI 0.2 to 2.0 ) . Patients in both groups were satisfied with the care provided by the physiotherapist . CONCLUSION Massage reduced the severity of pain in labour , despite not changing its characteristics and location Background : Labor pain is one of the severest pains that cause many women request cesarean section for fear of pain . Thus , controlling labor pain is a major concern of maternity care . Nowadays , interest in non-pharmacological pain relief methods has been increased because of their lower side effects . The effects of discrete heat and cold on decreasing labor pain have been reported but there was no evaluation of the effects of simultaneous heat and cold . The aim of this study was to investigate the effect of intermittent heat and cold on pain severity and childbirth outcomes . Material s and Methods : This study was a r and omized controlled trial . Sixty-four nulliparous women with term , One fetus , and low-risk pregnancy were divided into the intervention ( 32 participants ) and the control group ( 32 participants ) by r and om allocation . Excluding criteria were : administration of pain relief drugs , skin disease in the field of intervention , fetal distress , bleeding , fever , and disagreement with participation in the study . Warm and cold packs were used intermittently on low back and lower abdomen during the first phase and on perineum during the second phase of labor . Pain intensity was assessed with Visual Analogue Scale . Descriptive statistic , chi square , and t-test were used for data analysis . Results : There were no significant differences in demographic and midwifery characteristics and the baseline pain between two groups . The pain was significantly lower in intervention group during the first and second phases of labor . Duration of the first and third phases of labor was shorter in the case group . There were no significant differences in type of delivery , perineal laceration , oxytocin uptake , fetal heart rate , and APGAR between two groups . Discussion : Local warming with intermittent cold pack can reduce labor pain without adverse effects on maternal and fetal outcomes . It is an inexpensive and simple method . Conclusion : Intermittent local heat and cold therapy is a no pharmalogical , safe and effective method to relief labor pain OBJECTIVE To determine the effect of breathing techniques and nurse-administered massage on the pain perception of pregnant woman during labour . SETTING AND PARTICIPANTS The present study was conducted among pregnant women ( 75 % primiparous ) admitted to the SSK Bakirkoy Women and Children 's Hospital ( Istanbul , Turkey ) between January 1 , and September 1 , 2000 . The patients were in their 38th to 42nd week of pregnancy , not at high risk and expected to have normal vaginal delivery . They were selected from volunteers by nonr and om sampling . STUDY DESIGN The present study involved 40 cases , with 20 in the experimental group and 20 in the control group . Data were obtained through the visual analogue scale , inspection form , observation form and postnatal interview form . The study investigators provided information about labour , breathing techniques and massage to the pregnant women assigned to the experimental group at the beginning of labour ( latent phase ) . A study investigator also accompanied them during labour . These women received nurse-administered massage and were encouraged to breathe and perform self-administered massage . They were also instructed to change their positions and to relax . RESULTS AND CONCLUSION Study results demonstrated that nursing support and patient-directed education concerning labour and nonpharmacological pain control methods ( eg , breathing and cutaneous stimulation techniques ) were effective in reducing the perception of pain by pregnant women ( when provided in the latent labour phase before delivery ) , leading to a more satisfactory birth experience AIM Reduction of labor pain is one of the most important aspects of obstetric care . Heat therapy , typically applied to the woman 's back , lower abdomen , groin , and /or perineum during last stage of labor , is an easy pain relief method that does not require highly skilled care . The effectiveness of heat ther Output:	Massage may have a role in reducing pain , and improving women 's emotional experience of labour .
MS21261	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Our purpose was to measure the agreement , reliability , construct validity , and feasibility of a measurement tool to assess systematic review s ( AMSTAR ) . STUDY DESIGN AND SETTING We r and omly selected 30 systematic review s from a data base . Each was assessed by two review ers using : ( 1 ) the enhanced quality assessment question naire ( Overview of Quality Assessment Question naire [ OQAQ ] ) ; ( 2 ) Sacks ' instrument ; and ( 3 ) our newly developed measurement tool ( AMSTAR ) . We report on reliability ( interobserver kappas of the 11 AMSTAR items ) , intraclass correlation coefficients ( ICCs ) of the sum scores , construct validity ( ICCs of the sum scores of AMSTAR compared with those of other instruments ) , and completion times . RESULTS The interrater agreement of the individual items of AMSTAR was substantial with a mean kappa of 0.70 ( 95 % confidence interval [ CI ] : 0.57 , 0.83 ) ( range : 0.38 - 1.0 ) . Kappas recorded for the other instruments were 0.63 ( 95 % CI : 0.38 , 0.78 ) for enhanced OQAQ and 0.40 ( 95 % CI : 0.29 , 0.50 ) for the Sacks ' instrument . The ICC of the total score for AMSTAR was 0.84 ( 95 % CI : 0.65 , 0.92 ) compared with 0.91 ( 95 % CI : 0.82 , 0.96 ) for OQAQ and 0.86 ( 95 % CI : 0.71 , 0.94 ) for the Sacks ' instrument . AMSTAR proved easy to apply , each review taking about 15 minutes to complete . CONCLUSIONS AMSTAR has good agreement , reliability , construct validity , and feasibility . These findings need confirmation by a broader range of assessors and a more diverse range of review Four experiments explored the interrelations between working memory , attention , and eye movements . Observers had to identify a tilted line amongst vertical distractors . Each line was surrounded by a colored shape that could be precued by a matching item held in memory . Relative to a neutral baseline , in which no shapes matched the memory item , search was more efficient when the memory cue matched the shape containing the target , and it was less efficient when the cued stimulus contained a distractor . Cuing affected the shortest reaction times and the first saccade in search . The effect occurred even when the memory cue was always invalid but not when the cue did not have to be held in memory . There was also no evidence for priming effects between consecutive trials . The results suggest that there can be early , involuntary top-down directing of attention to a stimulus matching the contents of working memory Because there have been few longitudinal investigations of integrative etiological theories of bulimia nervosa , this study prospect ively tested the dual-pathway model using r and om regression growth curve models and data from a 3-wave community sample of adolescent girls ( N = 231 ) . Initial pressure to be thin and thin-ideal internalization predicted subsequent growth in body dissatisfaction , initial body dissatisfaction predicted growth in dieting and negative affect , and initial dieting and negative affect predicted growth in bulimic symptoms . There was prospect i ve evidence for most of the hypothesized mediational effects . Results are consistent with the assertion that pressure to be thin , thin-ideal internalization , body dissatisfaction , dieting , and negative affect are risk factors for bulimic pathology and provide support for the dual-pathway model BACKGROUND Attention bias modification treatment ( ABMT ) is a novel treatment for anxiety disorders . Although a number of other meta-analytic review s exist , the purpose of the present meta- analysis is to examine issues unaddressed in prior review s. Specifically , the review estimates the efficacy of ABMT in clinical ly anxious patients and examines the effect of delivery context ( clinic vs. home ) on symptom reduction . METHODS A literature search using PsychInfo and Web of Science data bases was performed . Only r and omized controlled trials ( RCTs ) examining dot-probe-based ABMT in clinical ly diagnosed anxious patients were included . From 714 articles located through the search , 36 ABMT studies were identified and 11 studies met inclusion criteria ( N = 589 patients ) . RESULTS ABMT was associated with greater clinician-rated reductions in anxiety symptoms relative to control training : between-groups effect ( d = 0.42 , P = .001 , confidence interval ( CI ) = 0.18 - 0.66 ) , contrast of within-group effects ( Q = 7.25 , P < .01 ) . More patients in the treatment group no longer met formal diagnostic criteria for their anxiety disorder posttreatment relative to patients in the control condition ( P < .05 ) . Analyses of patients ' self-reported anxiety were nonsignificant for the between-groups contrast ( P = .35 ) , and were at a trend level of significance for the contrast between the within-group effects ( P = .06 ) . Moderation analysis of the between-groups effect revealed a significant effect for ABMT delivered in the clinic ( d = 0.34 , P = 0.01 , CI = 0.07 - 0.62 ) , and a nonsignificant effect for ABMT delivered at home ( d = -0.10 , P = 0.40 , CI = -0.33 - 0.13 ) . CONCLUSIONS The current meta- analysis provides support for ABMT as a novel evidence d-based treatment for anxiety disorders . Overall , ABMT effects are mainly evident when it is delivered in the clinic and when clinical outcome is evaluated by a clinician . More RCTs of ABMT in specific anxiety disorders are warranted Output:	METHOD Electronic data bases were queried for review s of neurocognitive domains ( i.e. , inhibitory control , decision-making , central coherence , set-shifting , working memory , and attention bias ) in EDs , which identified 28 systematic and meta-analytic review s. RESULTS Broadly , the literature indicates deficits across these neurocognitive domains in EDs , though heterogeneity was noted in the magnitude of these effects , which varied to some extent across ED subtypes , sample characteristics , and method ological approaches .
MS21262	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: One hundred thirty patients with high grade osteosarcoma were enrolled in a r and omized prospect i ve multidisciplinary treatment that included intraarterial chemotherapy , local irradiation , limb salvage surgery , and prophylactic whole lung irradiation . The patients were evaluated to stage the prognostic factors . In a multivariate analysis , a minimal level of serum lactic acid dehydrogenase less than 300 IU/L showed a significant prognostic value . The history of trauma before diagnosis of disease , local irradiation of the affected site , histologic response to preoperative multidisciplinary therapy , and prophylactic whole lung irradiation were associated with significantly better prognosis in the log rank test . Patient age , site of the primary tumor , presentation of fracture , pathologic subtype , signs and symptoms , serum alkaline phosphatase level , and erythrocyte sedimentation rate were not found to be prognostic factors . The 9-year survival rate of the whole group was 55 % Output:	In this meta- analysis , elevated serum levels of alkaline phosphatase were associated with an increased risk of overall mortality and disease progression in patients with hormone-sensitive prostate cancer . In contrast , those were not associated with an increased risk of cancer-specific mortality . Alkaline phosphatase was independently associated with overall survival in both patients with “ high-volume ” and “ low-volume ” hormone-sensitive prostate cancer .
MS21263	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE The purpose of this prospect i ve clinical study was to evaluate peri-implant soft-tissue conditions and esthetic fulfillment during a 3-year follow-up period following prosthetic rehabilitation . MATERIAL AND METHODS As part of a prospect i ve multi-center study , 152 ITI dental implants were placed in 80 patients in the maxillary anterior region . Fifty-nine crowns ( 38.82 % ) were cement retained , while 93 ( 61.18 % ) crowns were screw retained . At loading and 3 , 6 , 12 and 36 months post-loading , modified plaque index ( MPI ) , sulcus bleeding index ( SBI ) , keratinized mucosa ( KM ) , gingival level ( GL ) , and esthetic fulfillment were recorded . RESULTS All patients completed the study and no complications were reported . While statistically not significant at all time points , cement-retained crowns seemed to present a worsening trend in MPI and SBI scores . Interestingly , screw-retained crowns seemed to present an opposite picture , their MPI and SBI scores improved over time . While plaque accumulation , prophylaxis and depth of crown margin significantly affected levels of sulcus bleeding , prophylaxis alone played a key role in reducing plaque accumulation . No soft tissue recession was observed in either cement- or screw-retained crowns up to 3 years post-loading . Esthetic fulfillment survey revealed that patients did not have a preference for crown types ; however , dentists favored cement-retained over screw-retained crowns . CONCLUSIONS Peri-implant soft tissues responded more favorably to screw-retained crowns when compared with cement-retained crowns . However , no soft-tissue recession was observed in either type of crowns . Cement-retained crowns were preferred by dentists , while patients were equally satisfied with either type of crowns they received The aim of the present study was to identify the peri-implant conditions ( bleeding on probing ( BOP ) , pocket probing depth ( PPD ) , modified plaque index ( mPI ) ) and marginal bone loss ( MBL , marginal bone level change between follow-up and occlusal loading ) around cemented and screw-retained posterior single crowns on tissue-level implants . The study was a retrospective cohort study with up to 4 years ( mean 2.5 years ) follow-up . Patients with either cemented or screw-retained crowns in posterior regions were included . Implant survival , technical complications , BOP , PPD , mPI , MBL , biologic complications ( peri-implant mocositis and peri-implantitis ) were evaluated . Mann-Whitney U test was used to test the difference between the screw-retained group ( SG ) and cemented group ( CG ) . 176 patients ( SG : 94 , CG : 82 ) were included . The implant survival rates were 100 % in SG and 98.8 % in CG . Prosthetic screw loosening was found in 8 restorations ( 8.7 % ) at follow-up visit . Peri-implant mucositis rate was significantly higher in the SG group ( 42.1 % ) than that in the CG group ( 32.2 % ) ( P = 0.04 ) . Six patients ( 6.38 % ) in the screw-retained group and 5 patients ( 6.10 % ) in the cemented group were diagnosed with peri-implantitis , the difference did not reach statistical significance ( P>0.05 ) . No significant difference of PPD , mPI and MBL were found between two groups ( P = 0.11 , 0.13 and 0.08 , respectively ) . High implant survival rates were achieved in both groups . Cemented single crowns on tissue-level implants showed comparable peri-implant conditions in comparison with two-piece screw-retained crowns . Well- design ed prospect i ve cohort or r and omized controlled clinical trials with longer follow-up are needed to confirm the result PURPOSE The aim of this study was to evaluate the survival and success of screw-retained versus cement-retained implant restorations in immediately loaded implants at 8-year follow-up . MATERIAL S AND METHODS Patients who were scheduled for full-arch ceramic prosthetic restorations were divided into two groups by r and omization : in one group , prosthetic frameworks were screwed onto implants ( screw-retained group , SRG ) , and in the second group , the frameworks were cemented on abutments ( cement-retained group , CRG ) . Dental implants were placed both in post extraction and in healed sites . A temporary full-arch prosthesis was placed immediately after implant placement . Intraoral digital radiographic examinations ( evaluating marginal bone levels ) were made at baseline , 6 months , and each year after implant placement . RESULTS In 28 patients , 24 full arches and 192 implants were placed in the maxilla and 10 full arches and 80 implants in the m and ible ( 17 rehabilitations in each group ) . After an 8-year follow-up period , a survival rate of 99.27 % was reported for all implants . Within the first year after implant placement , bone loss was recorded as follows : the CRG showed mean bone levels of -1.23 ± 0.45 mm , while the SRG showed mean bone levels of -1.01 ± 0.33 mm . After a 3-year follow-up , a slight increase was found ( 0.30 ± 0.25 mm in CRG and 0.45 ± 0.29 mm in SRG ) . After that point , marginal bone levels remained stable over time , up to the 8-year follow-up . No statistically significant differences were found between groups ( P > .05 ) . CONCLUSION Definitive cement- and screw-retained ceramic restorations are highly predictable , biocompatible , and esthetically pleasing , and the two groups presented no statistically significant differences in bone loss PURPOSE The purpose of this controlled prospect i ve clinical study was to compare cemented and screw-retained implant-supported single-tooth crowns followed for 4 years following prosthetic rehabilitation with respect to peri-implant marginal bone levels , peri-implant soft tissue parameters , and prosthetic complications . MATERIAL S AND METHODS Twelve consecutive patients were selected from a patient population attending the Implantology Department at the University of Padova . They all presented with single-tooth bilateral edentulous sites in the canine/premolar/molar region with adequate bone width , similar bone height at the implant sites , and an occlusal scheme that allowed for the establishment of identical occlusal cusp/fossa contacts . Each patient received 2 identical implants ( 1 in each edentulous site ) . One was r and omly selected to be restored with a cemented implant-supported single-tooth crown , and the other was restored with a screw-retained implant-supported single-tooth crown . Data on peri-implant marginal bone levels and on soft tissue parameters were collected 4 years after implant placement and analyzed to determine whether there was a significant difference with respect to the method of retention ( cemented versus screw-retained ) . RESULTS All patients completed the study . All 24 implants survived , result ing in a cumulative implant success rate of 100 % . Statistical analysis revealed no significant differences between the 2 groups with respect to peri-implant marginal bone levels and soft tissue parameters . DISCUSSION The data obtained with this study suggested that the choice of cementation versus screw retention for single-tooth implant restorations is likely not based on clinical results but seems to be based primarily on the clinician 's preference . CONCLUSIONS Within the limitations of this study , the results indicate that there was no evidence of different behavior of the peri-implant marginal bone and of the peri-implant soft tissue when cemented or screw-retained single-tooth implant restorations were provided for this patient population Output:	The keywords , such as " Screw versus Cement Retained Fixed Implant Supported Reconstructions , " " Screw Retained Fixed Implant . " " Results No significant difference was found between the screw-retained and cemented retained implant supported reconstructions . Dental implants are associated with complications leading to implant failure based on the type of restoration that is being used ; cement-retained restoration and screw-retained restoration . Conclusion Screw-retained implant-supported reconstructions were found to pose less biological and technological complications . Retention of the tooth is more stable and functional when implantation is selected based on the efficiency of a treatment procedure
MS21264	*TASK* the task is to summarize an input biomedical literature in six sentences *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 . Single blind r and omized study . Objectives . To compare the effectiveness of lumbar instrumented fusion with cognitive intervention and exercises in patients with chronic low back pain and disc degeneration . Summary of Background Data . To the authors ’ best knowledge , only one r and omized study has evaluated the effectiveness of lumbar fusion . The Swedish Lumbar Spine Study reported that lumbar fusion was better than continuing physiotherapy and care by the family physician . Patients and Methods . Sixty-four patients aged 25–60 years with low back pain lasting longer than 1 year and evidence of disc degeneration at L4–L5 and /or L5–S1 at radiographic examination were r and omized to either lumbar fusion with posterior transpedicular screws and postoperative physiotherapy , or cognitive intervention and exercises . The cognitive intervention consisted of a lecture to give the patient an underst and ing that ordinary physical activity would not harm the disc and a recommendation to use the back and bend it . This was reinforced by three daily physical exercise sessions for 3 weeks . The main outcome measure was the Oswestry Disability Index . Results . At the 1-year follow-up visit , 97 % of the patients , including 6 patients who had either not attended treatment or changed groups , were examined . The Oswestry Disability Index was significantly reduced from 41 to 26 after surgery , compared with 42 to 30 after cognitive intervention and exercises . The mean difference between groups was 2.3 ( −6.7 to 11.4 ) ( P = 0.33 ) . Improvements inback pain , use of analgesics , emotional distress , life satisfaction , and return to work were not different . Fear-avoidance beliefs and fingertip-floor distance were reduced more after nonoperative treatment , and lower limb pain was reduced more after surgery . The success rateaccording to an independent observer was 70 % after surgery and 76 % after cognitive intervention and exercises . The early complication rate in the surgical group was 18 % . Conclusion . The main outcome measure showed equal improvement in patients with chronic low back pain and disc degeneration r and omized to cognitive intervention and exercises , or lumbar fusion Study Design . A prospect i ve , r and omized , multicenter , Food and Drug Administration-regulated Investigational Device Exemption clinical trial . Objective . To evaluate the safety and effectiveness of the ProDisc ® -L ( Synthes Spine , West Chester , PA ) lumbar total disc replacement compared to circumferential spinal fusion for the treatment of discogenic pain at 1 vertebral level between L3 and S1 . Summary of Background Data . As part of the Investigational Device Exemption clinical trial , favorable single center results of lumbar total disc replacement with the ProDisc ® -L have been reported previously . Methods . Two hundred eighty-six ( 286 ) patients were treated on protocol . Patients were evaluated before and after surgery , at 6 weeks , 3 , 6 , 12 , 18 , and 24 months . Evaluation at each visit included patient self- assessment s , physical and neurologic examinations , and radiographic evaluation . Results . Safety of ProDisc ® -L implantation was demonstrated with 0 % major complications . At 24 months , 91.8 % of investigational and 84.5 % of control patients reported improvement in the Oswestry Low Back Pain Disability Question naire ( Oswestry Disability Index [ ODI ] ) from preoperative levels , and 77.2 % of investigational and 64.8 % of control patients met the ≥15 % Oswestry Disability Index improvement criteria . Overall neurologic success in the investigational group was superior to the control group ( 91.2 % investigational and 81.4 % control ; P = 0.0341 ) . At 6 weeks and 3 months follow-up time points , the ProDisc ® -L patients recorded SF-36 Health Survey scores significantly higher than the control group ( P = 0.018 , P = 0.0036 , respectively ) . The visual analog scale pain assessment showed statistically significant improvement from preoperative levels regardless of treatment ( P < 0.0001 ) . Visual analog scale patient satisfaction at 24 months showed a statistically significant difference favoring investigational patients over the control group ( P = 0.015 ) . Radiographic range of motion was maintained within a normal functional range in 93.7 % of investigational patients and averaged 7.7 ° . Conclusions . ProDisc ® -L has been found to be safe and efficacious . In properly chosen patients , ProDisc ® -L has been shown to be superior to circumferential fusion by multiple clinical criteria Mixed treatment comparison ( MTC ) meta- analysis is a generalization of st and ard pairwise meta- analysis for A vs B trials , to data structures that include , for example , A vs B , B vs C , and A vs C trials . There are two roles for MTC : one is to strengthen inference concerning the relative efficacy of two treatments , by including both ' direct ' and ' indirect ' comparisons . The other is to facilitate simultaneous inference regarding all treatments , in order for example to select the best treatment . In this paper , we present a range of Bayesian hierarchical models using the Markov chain Monte Carlo software WinBUGS . These are multivariate r and om effects models that allow for variation in true treatment effects across trials . We consider models where the between-trials variance is homogeneous across treatment comparisons as well as heterogeneous variance models . We also compare models with fixed ( unconstrained ) baseline study effects with models with r and om baselines drawn from a common distribution . These models are applied to an illustrative data set and posterior parameter distributions are compared . We discuss model critique and model selection , illustrating the role of Bayesian deviance analysis , and node-based model criticism . The assumptions underlying the MTC models and their parameterization are also discussed Abstract Objectives To assess the clinical effectiveness of surgical stabilisation ( spinal fusion ) compared with intensive rehabilitation for patients with chronic low back pain . Design Multicentre r and omised controlled trial . Setting 15 secondary care orthopaedic and rehabilitation centres across the United Kingdom . Participants 349 participants aged 18 - 55 with chronic low back pain of at least one year 's duration who were considered c and i date s for spinal fusion . Intervention Lumbar spine fusion or an intensive rehabilitation programme based on principles of cognitive behaviour therapy . Main outcome measure The primary outcomes were the Oswestry disability index and the shuttle walking test measured at baseline and two years after r and omisation . The SF-36 instrument was used as a secondary outcome measure . Results 176 participants were assigned to surgery and 173 to rehabilitation . 284 ( 81 % ) provided follow-up data at 24 months . The mean Oswestry disability index changed favourably from 46.5 ( SD 14.6 ) to 34.0 ( SD 21.1 ) in the surgery group and from 44.8 ( SD14.8 ) to 36.1 ( SD 20.6 ) in the rehabilitation group . The estimated mean difference between the groups was –4.1 ( 95 % confidence interval –8.1 to –0.1 , P = 0.045 ) in favour of surgery . No significant differences between the treatment groups were observed in the shuttle walking test or any of the other outcome measures . Conclusions Both groups reported reductions in disability during two years of follow-up , possibly unrelated to the interventions . The statistical difference between treatment groups in one of the two primary outcome measures was marginal and only just reached the predefined minimal clinical difference , and the potential risk and additional cost of surgery also need to be considered . No clear evidence emerged that primary spinal fusion surgery was any more beneficial than intensive rehabilitation Study Design . R and omized , controlled , multicenter , investigational device exemption trial . Objective . To investigate the safety and effectiveness of the first two-piece , metal-on-metal lumbar disc prosthesis for treating patients with single-level degenerative disc disease . Summary of Background Data . For patients with degenerative disc disease unresponsive to conservative measures , lumbar disc arthroplasty provides an alternative to fusion design ed to relieve persistent discogenic pain and maintain motion . Methods . After 2:1 r and omization , 577 patients were treated in either the investigational group ( 405 ) , receiving lumbar disc arthroplasty , or the control group ( 172 ) , receiving anterior lumbar interbody fusion . Patients were evaluated preoperatively , at surgery/discharge , and at 1.5 , 3 , 6 , 12 , and 24 months after surgery . The primary study endpoint was overall success , a composite measure of safety and effectiveness as recommended by the Food and Drug Administration and defined in the protocol . Results . Both treatment groups demonstrated significant improvements compared with preoperative status . The investigational group had statistically superior outcomes ( P < 0.05 ) at all postoperative evaluations in Oswestry Disability Index , back pain , and Short Form-36 Physical Component Summary scores as well as patient satisfaction . Investigational patients had longer surgical times ( P < 0.001 ) and greater blood loss ( P < 0.001 ) than did control patients ; however , hospitalization stays were similar for both groups . Investigational patients had fewer implant or implant/surgical procedure-related adverse events ( P < 0.001 ) . Return-to-work intervals were reduced for investigational patients . Disc height and segmental angular motion were maintained throughout the study in the investigational group . In the investigational group , overall success superiority was found when compared to the control group as defined by the Food and Drug Administration Investigational Device Exemption protocol . Conclusion . The investigational group consistently demonstrated statistical superiority versus fusion on key clinical outcomes including improved physical function , reduced pain , and earlier return to work Purpose To compare the 9-year outcome in patients with chronic low back pain treated by instrumented lumbar fusion versus cognitive intervention and exercises . Methods The main outcome measure was the Oswestry Disability Index ( ODI ) . Secondary outcome measures included pain , fear-avoidance beliefs , trunk muscle strength , medication , and return to work . Results One-third of the patients r and omized to cognitive intervention and exercises had crossed over and been operated and one-third of the patients allocated to lumbar fusion had been re-operated . The intention-to-treat analysis detected no differences between the two groups . The mean adjusted treatment effect for ODI was 1.9 ( 95 % CI −7.8 to 11.6 ) . Analysed according to the treatment received , more operated patients used pain medication and were out of work . Conclusions The outcome at 9 years was not different between instrumented lumbar fusion and cognitive intervention and exercises The study design includes a prospect i ve , r and omised controlled study comparing total disc replacement ( TDR ) with posterior fusion . The main objective of this study is to compare TDR with lumbar spinal fusion , in terms of clinical outcome , in patients referred to a spine clinic for surgical evaluation . Fusion is effective for treating chronic low back pain ( LBP ) , but has drawbacks , such as stiffness and possibly adjacent level degradation . Motion-preserving options have emerged , of which TDR is frequently used because of these drawbacks . How the results of TDR compare to fusion , however , is uncertain . One hundred and fifty-two patients with a mean age of 40 years ( 21–55 ) were included : 90 were women , and 80 underwent TDR . The patients had not responded to a conservative treatment programme and suffered from predominantly LBP , with varying degrees of leg pain . Diagnosis was based on clinical examination , radiographs , MRI , and in unclear cases , diagnostic injections . Outcome measures were global assessment ( GA ) , VAS for back and leg pain , Oswestry Disability Index , SF36 and EQ5D at 1 and 2 years . Follow-up rate was 100 % , at both 1 and 2 years . All outcome variables improved in both groups between preoperative and follow-up assessment . The primary outcome measure , GA , revealed that 30 % in the TDR group and 15 % in the fusion group were totally pain-free at 2 years ( P = 0.031 ) . TDR patients had reached maximum recovery in virtually all variables at 1 year , with significant differences compared to the fusion group . The fusion patients continued to improve and at 2 years had results similar to TDR patients apart from numbers of pain-free . Complications and reoperations were similar in both groups , but pedicle screw removal as additive surgery , was frequent in the fusion group . One year after surgery , TDR was superior to spinal fusion in clinical outcome , but this difference had diminished by 2 years , apart from ( VAS for back pain and ) numbers of pain-free . The long-term benefits have yet to be examined BACKGROUND Disc replacement arthroplasty previously has been shown to be an effective alternative to spine fusion for the treatment of single-level lumbar degenerative disc disease . The purpose of the present study was to determine the twenty-four-month results of a clinical trial of the ProDisc-L total disc replacement as compared with spinal fusion for the treatment of degenerative disc disease at two contiguous vertebral levels from L3 to S1 . METHODS A total of 237 patients were treated in a r and omized controlled trial design ed as a non-inferiority study for regulatory application purpose s. Blocked r and omization was performed with use of a 2:1 ratio of total disc arthroplasty to circumferential arthrodesis . Evaluations , including patient self- assessment s , physical and neurological examinations , and radiographic examinations , were performed preoperatively , six weeks postoperatively , and three , six , twelve , eighteen , and twenty-four months postoperatively . RESULTS At twenty-four months , 58.8 % ( eighty-seven ) of 148 patients in the total disc replacement group were classified as a statistical success , compared with 47.8 % ( thirty-two ) of sixty-seven patients in the arthrodesis group ; non-inferiority was demonstrated . The mean Oswestry Disability Index in both groups significantly improved from baseline ( p < 0.00 Output:	Conclusions : All 4 treatments provided some benefit to patients with chronic LBP . According to the MTC analysis , TDR may be the most effective treatment and PT the least effective treatment for chronic LBP . This review is based on a limited number of RCT studies and does not support any 1 treatment modality for all patients
MS21265	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Serial circulating tumor cell ( CTC ) counts have demonstrated predictive and prognostic value in patients with metastatic breast , colorectal , and prostate cancer . In a phase III study of pegylated liposomal doxorubicin ( PLD ) with trabectedin vs. PLD for relapsed ovarian cancer , we evaluated the correlation , if any , between numbers of CTCs and progression free survival , ( PFS ) and overall survival ( OS ) . METHODS CTCs were isolated from peripheral blood ( 10 mL ) using the Cell Search system and reagents ( Veridex ) . A CTC is defined as EpCAM+ , cytokeratin+ , CD45- , and is positive for the nuclear stain DAPI . The normal reference range for Cell Search is < 2 CTC/7.5 mL of blood . Hazard ratios adjusted for known prognostic factors were estimated by Cox regression . RESULTS Two-hundred sixteen patients had baseline CTC measurements of which 111 ( 51.4 % ) were r and omized to the trabectedin+PLD arm ; 143/216 patients ( 66.2 % ) were platinum-sensitive . Thirty-one of 216 patients ( 14.4 % ) had 2 or more CTCs detected prior to the start of therapy ( range 2 - 566 ) . Univariate Cox regression analyses indicated that patients with ≥2 CTCs prior to therapy had 1.89- ( p=0.003 ) and 2.06-fold ( p=0.003 ) higher risk for progression and death respectively . Multivariate analyses that include baseline CA-125 , platinum sensitivity status , largest diameter lesion , number of tumor lesions , ECOG PS , and tumor grade show that patients with elevated baseline CTC had 1.58- ( p=0.058 ) and 1.54-fold ( p=0.096 ) higher risk for progression and death respectively . CONCLUSIONS Results from this study indicate that elevated numbers of CTCs impart an unfavorable prognosis for ovarian cancer patients OBJECTIVE Serum CA-125 values have been advocated in the monitoring of ovarian cancer patients receiving intravenous ( IV ) chemotherapy . This evaluation sought to determine if the CA-125 test can be used to monitor treatment effect among patients receiving intraperitoneal chemotherapy ( IP ) . METHODS Patient charts from a phase III clinical trial ( GOG 172 ) were retrospectively review ed . Serum CA-125 levels prior to each cycle of therapy were collected and compared between the IV and IP chemotherapy delivery . The association between CA-125 and progression-free survival ( PFS ) or overall survival ( OS ) was estimated and the homogeneity of the results between IP and IV chemotherapy was assessed . RESULTS A total of 177 patients were treated with IV chemotherapy and 165 patients with IP chemotherapy with CA-125 data available were included in this analysis . The observed difference was not statistically significant in median CA-125 levels between the IV and IP arms at any time point ( P>0.05 for all ) . Following surgery and adjuvant chemotherapy , patients with an abnormal CA-125 > 35 U/ml were 2.45 times more likely to have disease progression ( 95 % CI : 1.52 - 3.95 , P<0.001 ) and 2.78 times more likely to die of disease ( 95 % CI : 1.66 - 4.65 , P<0.001 ) , compared to those with a CA-125 < 35 U/ml . These results were consistent with IP and IV chemotherapy . CONCLUSION Serum CA-125 levels decrease in a similar manner during IP chemotherapy when compared to IV chemotherapy . Serum CA-125 algorithms for monitoring treatment effect that have been established for IV chemotherapy may also be applied for patients receiving IP chemotherapy OBJECTIVE Patients with persistent/recurrent epithelial ovarian cancer/ primary peritoneal cancer ( EOC/PPC ) have limited treatment options . AKT and PI3 K pathway activation is common in EOC/PPC , result ing in constitutive activation of downstream mTOR . The GOG conducted a phase II evaluation of efficacy and safety for the mTOR inhibitor , temsirolimus in EOC/PPC and explored circulating tumor cells ( CTC ) and AKT/mTOR/downstream tumor markers . METHODS Eligible women with measurable , persistent/recurrent EOC/PPC who had received 1 - 3 prior regimens were treated with 25 mg weekly IV temsirolimus until progression or intolerable toxicity . Primary endpoints were progression-free survival ( PFS ) ≥6-months , tumor response , and toxicity . Cell Search ® system was used to examine CTC , and AKT/mTOR/downstream markers were evaluated by archival tumor immunohistochemistry . Kendall 's tau-b correlation coefficient ( r ) and Cox regression modeling were used to explore marker associations with baseline characteristics and outcome . RESULTS Sixty patients were enrolled in a two-stage sequential design . Of 54 eligible and evaluable patients , 24.1 % ( 90 % CI 14.9%-38.6 % ) had PFS ≥6 months ( median 3.1 months ) , 9.3 % ( 90 % CI 3.7%-23.4 % ) experienced a partial response . Grade 3/4 adverse events included metabolic ( 8) , gastrointestinal ( 8) , pain ( 6 ) , constitutional ( 5 ) and pulmonary ( 4 ) . Suggested associations were between cyclin D1 and PFS ≥6 months , PFS or survival ; positive CTC pre-treatment and lack of response ; and high CTC expression of M30 and PFS ≥6 months/longer PFS . CONCLUSIONS Temsirolimus appears to have modest activity in persistent/recurrent EOC/PPC ; however , PFS is just below that required to warrant inclusion in phase III studies in unselected patients . Cyclin D1 as a selection marker and CTC measures merit further study BACKGROUND Our group evaluated the risk of recurrence for optimally treated advanced epithelial ovarian cancer ( adEOC ) in patients with a low-level rising serum CA-125 concentration within the normal range ( 0 - 35 kU/l ) . In addition , we tested the new proposed early CA-125 signal of progressive disease ( EPD ) criterion in the same study population . PATIENTS AND METHODS Patients treated from 1998 to 2006 for adEOC were identified at our institution . Inclusion criteria were as follows : CA-125 at time of diagnosis ( > 35 kU/l ) ; International Federation of Gynecology and Obstetrics stages III-IV treated with optimal primary treatment ; and complete response ( CR ) to primary treatment with normalization of CA-125 . RESULTS Median progression-free survival and overall survival for the recurrence group ( n = 60 ) were 17.7 and 38.2 months , respectively . The median follow-up time from CR to last contact was 40.2 months for patients in the nonrecurrence group ( n = 36 ) . An absolute increase in serum CA-125 levels of > or=5 kU/l compared with baseline CA-125 nadir values was significantly predictive of recurrence ( odds ratio for recurrence = 402.98 , P < 0.0001 ) . The progression date was pre date d by the EPD criterion in 77 % of patients with known progressive disease ( median , 58 days early ) with a sensitivity of 90 % , a positive predictive value of 96.4 % , and a false-positive rate of 5.6 % . CONCLUSIONS Among patients with optimally treated adEOC in complete remission , a low-level increase in serum CA-125 concentration within the normal range is a strong independent predictive factor for disease recurrence . In this patient population , future prospect i ve r and omized trials should consider the evaluation of the EPD criterion OBJECTIVE To determine whether circulating tumor cells ( CTCs ) , as detected and enumerated by the Veridex Cell Search system , could predict for clinical outcomes in women with newly diagnosed or recurrent epithelial ovarian cancer . METHODS Serial measurements of CTC s and paired serum CA125 were collected in a series of 78 women with newly diagnosed or recurrent ovarian cancer seen at our institution over a period of 15 months . Clinical data were abstract ed from patient medical records . CTCs were detected and enumerated by the Cell Search protocol , and patients were divided into CTC negative ( < 2 CTCs ) or positive ( ≥2 CTCs ) groups . CTC groups were correlated with clinical characteristics and outcomes . A longitudinal analysis of CTC change and CA125 trends was also performed . RESULTS At least one CTC was isolated from the peripheral blood of over 80 % of the women participating in this study , with a range from 0 to 8 . No correlations were observed between CTC numbers and clinical characteristics or outcomes . Although both serum CA125 and CTC number exhibited an overall significant decreasing trend over time , there was no correlation observed between change in CTCs and CA125 . CONCLUSION Using the FDA -approved Cell Search system , CTCs can be isolated from women with newly diagnosed or recurrent ovarian cancer . However , CTC numbers do not significantly correlate with clinical characteristics or patient outcomes . Future studies should focus on phenotypic characterization of CTCs and whether different isolation protocol s yield a higher number of CTCs or add prognostic value Output:	The presence of CTCs and DTCs is associated with adverse clinicopathological characteristics and poor clinical outcomes in ovarian cancer patients .
MS21266	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The aim of this study was to evaluate whether anterior cruciate ligament ( ACL ) reconstruction using the double bundle technique ( DB ) improves stability in the knee compared with the single bundle technique ( SB ) with the femoral tunnel in a more horizontal position ( 2 or 10 o’clock ) . We conducted a r and omized , prospect i ve study . Forty patients were r and omized to the DB group ( 20 patients ) and the SB group ( 20 patients ) . Four-str and ed semitendinosus and gracilis autologous grafts were used in the SB group and in the DB group the conventional four tunnel technique was carried out using the same tendons . The IKDC complete form was used for the preoperative evaluation , and in the follow-up the IKDC subjective knee evaluation form , IKDC current health assessment form and IKDC knee examination form were used . Anteroposterior ( AP ) laxity was evaluated by st and ardised and forced radiology in all patients . No significant preoperative between-group differences were found . During the follow-up , no differences were found between groups , except for significant between-group differences ( P < 0.05 ) between the preoperative and postoperative evaluations . The IKDC index also showed significant differences in the 2-year follow-up . Median scores increased from 48 ( range 41–54 ) to 81 ( range 75–87 ) ( P = 0.01 ) in the SB group and from 52 ( range 46–58 ) to 80 ( range 72–88 ) ( P = 0.02 ) in the DB group . There were no significant differences between the groups in terms of functional scores . In conclusion , the 2 and 10 o’clock placements showed no significant differences between SB and DB techniques in the pivot-shift test , manual and radiological anterior posterior laxity and IKDC scores . However , significant between-group differences were found between the preoperative and postoperative evaluations Twenty-six patients with anteroposterior ( AP ) laxity of the knee , associated with torn anterior cruciate ligament ( ACL ) , were prospect ively r and omized for arthroscopic lower femoral tunnel placed single- or double-bundle reconstruction using hamstring tendons . We evaluated AP and rotational stabilities under regular loads ( a 100-N anterior load and a 1.5-N m external – internal load ) before and after ACL reconstruction , comparing single- and double-bundle reconstruction with our original device for applying quantitative tibial rotation and the navigation system intraoperatively . No significant differences were found between the two groups in AP displacement and total range of tibial rotation at 30 ° and 60 ° of knee flexion . We found that a lower femoral tunnel placed single-bundle reconstruction reproduced AP and rotational stability as well as double-bundle reconstruction after reconstruction intraoperatively We conducted a prospect i ve r and omised study of anatomical single-bundle ( A-SB group ) versus double-bundle ( A-DB group ) anterior cruciate ligament ( ACL ) reconstruction using the hamstrings tendons . Twenty patients with unilateral ACL deficiency were r and omised into two groups . We created the bone tunnels at the position of the original insertion of the anteromedial bundle footprint and posterolateral bundle footprint in the A-DB group and at the central position between these two bundles in the A-SB group . All of the patients were tested before ACL reconstruction and one year after surgery . The KT-1000 measurements , isokinetic muscle peak torque and heel-height difference were evaluated and the general knee condition was assessed by Lysholm score . For pre- and postoperative stability assessment , we used the six-degrees-of-freedom of knee kinematic measurement system using an electromagnetic device ( the EMS ) for quantitative assessment during the Lachman test and the pivot shift test . There were no significant differences in the KT-1000 measurements , isokinetic muscle peak torque , heel-height difference , and Lysholm score at one-year follow-up between these two groups . The EMS data showed there were significant differences in the acceleration of the pivot shift test between the operated knee and the contralateral normal knees in the A-SB group . In conclusion , clinical outcomes were equally good in both groups . However , the EMS data showed the anatomical double-bundle ACL reconstruction tended to be biomechanically superior to the single-bundle reconstruction Purpose The purpose of this study was to compare subjective , objective and radiographic outcome of the lateralized single-bundle bone-patellar tendon-bone autograft with a non-anatomical double-bundle hamstring tendons autograft anterior cruciate ligament ( ACL ) reconstruction technique at long-term follow-up . Methods Seventy-nine non-consecutive r and omized patients ( 42 men ; 37 women ) with unilateral ACL insufficiency were prospect ively evaluated , before and after ACL reconstruction by means of the above-mentioned techniques , with a minimum follow-up of 8 years ( range 8–10 years ; mean 8.6 years ) . In the double-bundle hamstrings technique , we used one tibial and one femoral tunnel combined with one “ over-the-top ” passage , cortical staple ’s fixation and we left intact hamstrings ’ tibial insertion . Patients were evaluated subjectively and objective ly , using IKDC score , Tegner level , manual maximum displacement test with KT-2000 ™ arthrometer . Radiographic evaluation was performed according to IKDC grading system , and re-intervention rate for meniscal lesions was also recorded . Results The subjective and objective IKDC were similar in both groups while double-bundle hamstrings group showed significantly higher Tegner level ( P = 0.0007 ) , higher passive range of motion recovery ( P = 0.0014 ) , faster sport resumption ( P = 0.0052 ) , lower glide pivot-shift phenomenon ( P = 0.0302 ) and lower re-intervention rate ( P = 0.0116 ) compared with patellar tendon group . Radiographic evaluation showed significant lower objective degenerative changes in double-bundle hamstrings group at final follow-up ( P = 0.0056 ) . Conclusion Although both techniques provide satisfactory results , double-bundle ACL reconstruction shows better functional results , with a faster return to sport activity , a lower re-operation rate and lower degenerative knee changes Adequate reporting of r and omized , controlled trials ( RCTs ) is necessary to allow accurate critical appraisal of the validity and applicability of the results . The CONSORT ( Consoli date d St and ards of Reporting Trials ) Statement , a 22-item checklist and flow diagram , is intended to address this problem by improving the reporting of RCTs . However , some specific issues that apply to trials of nonpharmacologic treatments ( for example , surgery , technical interventions , devices , rehabilitation , psychotherapy , and behavioral intervention ) are not specifically addressed in the CONSORT Statement . Furthermore , considerable evidence suggests that the reporting of nonpharmacologic trials still needs improvement . Therefore , the CONSORT group developed an extension of the CONSORT Statement for trials assessing nonpharmacologic treatments . A consensus meeting of 33 experts was organized in Paris , France , in February 2006 , to develop an extension of the CONSORT Statement for trials of nonpharmacologic treatments . The participants extended 11 items from the CONSORT Statement , added 1 item , and developed a modified flow diagram . To allow adequate underst and ing and implementation of the CONSORT extension , the CONSORT group developed this elaboration and explanation document from a review of the literature to provide examples of adequate reporting . This extension , in conjunction with the main CONSORT Statement and other CONSORT extensions , should help to improve the reporting of RCTs performed in this field A total of 108 patients with unilateral instability of the knee , associated with rupture of the anterior cruciate ligament , was prospect ively r and omised for arthroscopic single- or double-bundle reconstruction of the ligament using hamstring tendons . The same post-operative rehabilitation protocol was used for all . The patients were followed up for a mean of 32 months ( 24 to 36 ) . We measured the anterior laxity and joint position sense at different angles of flexion of the knee to determine whether both bundles in the double-bundle reconstruction contributed to the stability of the joint and proprioception . No significant difference was found between the two groups with regard to anterior laxity measured by the KT-2000 arthrometer with the knee at 20 degrees or 70 degrees flexion nor with regard to proprioception . A notchplasty was required less often in the double- compared with the single-bundle reconstruction . We did not find any advantage in a double-bundle as opposed to a single-bundle reconstruction in terms of stability or proprioception Double-bundle anterior cruciate ligament ( ACL ) reconstruction is intended to replicate the anatomy and the function of the anteromedial and posterolateral bundles of the native ACL to improve patients ' satisfaction and knee stability . We prospect ively assigned 75 consecutive patients with an isolated ACL lesion to one of three sequential groups of 25 patients each . Group I received a single-bundle , single-incision transtibial ACL reconstruction . Groups II and III received a double-bundle reconstruction with a single-incision transtibial technique or a double-bundle , twoincision outside-in technique , respectively . We obtained subjective International Knee Documentation Committee and Knee Injury and Osteoarthritis Outcome Score evaluations and objective International Knee Documentation Committee scores and KT-1000 measurements preoperatively and at followup . All patients reached a minimum followup of 2 years . KT side-to-side difference in Groups I , II , and III were 2.4 , 1.6 and 1.4 mm , respectively . Group III had fewer patients with a positive pivot shift than Group I. The double-bundle double-incision outside-in ACL reconstruction result ed in improved anteroposterior stability and less residual pivot shift than single-incision single-bundle technique . Level of Evidence : Level II , therapeutic study . See Guidelines for Authors for a complete description of levels of evidence Several investigators have reported the presence of biomechanical , kinematic , anatomic , fiber orientation patterns and biological differences between the anteromedial bundle and the posterolateral bundle of ACL . The purpose of this prospect i ve r and omized study was to compare the clinical , instrumental and X-ray outcome of two ACL reconstruction techniques with hamstring tendons : one with a single intra-articular bundle associated to an extra-articular sling , the second with a more anatomic double-bundle technique that reproduces better the native ACL function . From an initial group of 100 patients who underwent ACL reconstruction , 72 patients ( 35 single bundle plus lateral plasty and 37 double bundle ) were evaluated with IKDC , Tegner score , KT2000 arthrometer , Activity Rating Scale , Psychovitality Question naire and Ahlback radiographic score at a mean 3 years follow-up . Double-bundle group showed significantly better results regarding IKDC , ROM , Activity Rating Scale and time to return to sport . Also KT 2000 showed significant differences in objective stability . The double-bundle technique for ACL reconstruction described in this paper has demonstrated significantly better subjective , objective and functional results compared with a double-str and ed hamstrings plus extra-articular sling at a minimum 3-year follow-up Double-bundle anterior cruciate ligament ( ACL ) reconstruction reproduces anteromedial and posterolateral bundles , and thus has theoretical advantages over conventional single-bundle reconstruction in controlling rotational torque in vitro . However , its superiority in clinical practice has not been proven . We analyzed rotational stability with three reconstruction techniques in 60 consecutive patients who were r and omly divided into three groups ( double-bundle , anteromedial single-bundle , posterolateral single-bundle ) . In the reconstructive procedure , the hamstring tendon was harvested and used as a free tendon graft . Followup examinations were performed 1 year after surgery . Anteroposterior laxity of the knee was examined with a KT-1000 arthrometer , whereas rotatory instability , as elicited by the pivot shift test , was assessed using a new measurement system incorporating three-dimensional electromagnetic sensors . Routine clinical evaluations , including KT examination , demonstrated no differences among the three groups . However , using the new measurement system , patients with double-bundle ACL reconstruction showed better pivot shift control of complex instability than patients with anteromedial and posterolateral single-bundle reconstruction . Level of Evidence : Level II , therapeutic study . See the Guideline for Authors for a complete description of levels of evidence Anatomical observation and biomechanical studies have shown that the anterior cruciate ligament ( ACL ) mainly consists of two distinct bundles , the anteromedial ( AM ) bundle and posterolateral ( PL ) bundle . Conventional single-bundle ACL reconstruction techniques have focused on the restoration of the AM bundle while giving limited attention to the PL bundle . The purpose of this prospect i ve , r and omized clinical study is to compare the outcomes of ACL reconstruction when using either double-bundle or single-bundle technique and bioabsorbable interference screw fixation , and similar rehabilitation with both techniques . Sixty-five patients were r and omized into either double-bundle ( n = 35 ) or single-bundle ( n = 30 ) ACL reconstruction with hamstring tendons and bioabsorbable screw ( Hexalon , Inion Company , Tampere , Finl and ) fixation in both groups . The evaluation methods were clinical examination , KT-1000 arthrometer measurements , radiographic evaluation , as well as International Knee Documentation Committee and Lysholm knee scores . There were no differences between the study groups preoperatively . For an average of 14 months of follow-up ( range 12–20 months ) , 30 patients of the double-bundle group and 29 patients of the single-bundle group were available ( 91 % ) . At the follow-up , the rotational stability , as evaluated by pivot shift test , was significantly better in the double- Output:	Data for pooling individual outcomes were available for a maximum of nine trials and 54 % of participants .There were no statistically or clinical ly significant differences between double-bundle and single-bundle reconstruction in the subjective functional knee scores ( subjective IKDC score , Tegner activity score , Lysholm score ) in the intermediate ( six months up to two years since surgery ) or long term ( two to five years from surgery ) . There is insufficient evidence to determine the relative effectiveness of double-bundle and single-bundle reconstruction for anterior cruciate ligament rupture in adults , although there is limited evidence that double-bundle ACL reconstruction has some superior results in objective measurements of knee stability and protection against repeat ACL rupture or a new meniscal injury .
MS21267	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: INTRODUCTION The aim of this prospect i ve clinical study was to evaluate the skeletal , dentoalveolar , and soft-tissue effects of maxillary protraction with miniplates compared with conventional facemask therapy and an untreated Class III control group . METHODS Forty-five subjects who were in prepubertal or pubertal skeletal growth periods were included in the study and divided into 3 groups of 15 patients each . All subjects had skeletal and dental Class III malocclusions with maxillary deficiency , vertically normal growth pattern , anterior crossbite , Angle Class III molar relationship , normal or increased overbite , and retrusive nasomaxillary complex . Before maxillary protraction , rapid maxillary expansion with a bonded appliance was performed in both treatment groups . In the first group ( MP+FM ) , consisting of 5 girls and 10 boys ( mean age , 10.91 years ) , facemasks were applied from 2 titanium miniplates surgically placed laterally to the apertura piriformis regions of the maxilla . The second group ( FM ) of 7 girls and 8 boys ( mean age , 10.31 years ) received maxillary protraction therapy with conventional facemasks applied from hooks of the rapid maxillary expansion appliance . The third group of 8 girls and 7 boys ( mean age , 10.05 years ) was the untreated control group . Lateral cephalometric films were obtained at the beginning and end of treatment or observation in all groups and analyzed according to a structural superimposition method . Measurements were evaulated statistically with Wilcoxon and Kruskal-Wallis tests . RESULTS Treatment periods were 6.78 and 9.45 months in the MP+FM and FM groups , respectively , and the observation period in the control group was 7.59 months . The differences were significant between the 3 groups ( P < 0.05 ) and the MP+FM and FM groups ( P < 0.001 ) . The maxilla moved forward for 2.3 mm in the MP+FM group and 1.83 mm in the FM group with maxillary protraction . The difference was significant between 2 groups ( P < 0.001 ) . The protraction rates were 0.45 mm per month in the MP+FM group and 0.24 mm per month in the FM group ( P < 0.001 ) . The maxilla showed anterior rotation after facemask therapy in the FM group ( P < 0.01 ) ; there was no significant rotation in the MP+FM group . Posterior rotation of the m and ible and increased facial height were more evident in the FM group compared with the MP+FM group ( P < 0.01 ) . Both the maxilla and the m and ible moved forward significantly in the control group . Protrusion and mesialization of the maxillary teeth in the FM group were eliminated in the MP+FM group . The maxillom and ibular relationships and the soft-tissue profile were improved remarkably in both treatment groups . CONCLUSIONS The undesired effects of conventional facemask therapy were reduced or eliminated with miniplate anchorage , and efficient maxillary protraction was achieved in a shorter treatment period The aim of this research was to evaluate , within a controlled clinical study , the effects of a Delaire-type facemask or a modified Jasper Jumper ( JJ ) used in the treatment of children with Class III malocclusions due to maxillary retrognathia on temporom and ibular disorders ( TMDs ) . Forty-six patients with Class III malocclusions referred for orthodontic treatment were divided into two groups , a test and a control . The test group comprised 33 r and omly chosen patients ( 15 females , 18 males ) aged 8 - 11 years . The control group included 13 patients ( eight females , five males ) with similar features . TMD assessment was performed before and after treatment using a two-axis question naire , the Research Diagnostic Criteria for Temporom and ibular Disorders ( RDC/TMDs ) . Qualitative data were evaluated using chi-square and McNemar tests . No statistically significant differences related to the presence of TMD were observed pre- or post-treatment ( P > 0.05 ) . The most commonly encountered diagnosis was arthralgia in the JJ group both before and after treatment . Evaluation of joint and muscle regions showed decreased symptoms , apart from the diagnosed discomforts , in the JJ group ( P < 0.05 ) . Reduced symptoms were observed in the Delaire group ; however , this reduction was not statistically significant . An increase , not considered to be statistically significant , was observed in the control group . The Delaire-type facemask and modified JJ used in the early phase of Class III malocclusion treatment did not result in TMD Background and Objective : When treating pronounced dentoalveolar compensation of a skeletal Class III malocclusion , preoperative decompensation frequently requires the extraction of maxillary lateral teeth and retraction of the incisors . In this context , maximum anchorage of the maxillary molars is frequently necessary to attain the significant increase in negative overjet that is desired . The aim of this study was to compare the quality of conventional and skeletal molar anchorage using mini-implants in association with pre-operative decompensation . Patients and Methods : Pre-operative decompensation involved the symmetric extraction of two lateral teeth from the maxilla as well as retraction of the front teeth in each of 20 patients with a marked skeletal Class III . The molar anchorage half of the patients received was conventional ( transpalatal arch ) while the other half were treated with skeletal anchorage via mini-implants inserted in the anterior palate . Study models were prepared and analyzed using a 3D scanner before and after space closure ( OrthoProof ) . We analyzed the bilateral degree of mesial molar migration and change in the transversal dimension ( DigiModel software ) . Results : All patients demonstrated mesial migration of the upper molars as a response to the load on the anchorage unit . The 4.21 mm ( ± 1.17 mm ) anchorage loss associated with conventional anchorage was greater than that of skeletal anchorage in the anterior palate ( 2.05 mm [ ± 1.39 mm ] ) . We observed a tendency towards transversal expansion in the molar region according to the design and thickness of the transpalatal arch . Conclusions : Skeletal molar anchorage proved to be more effective than the conventional anchorage . Hence , skeletal anchorage is preferable , especially when patients are in serious need of preoperative decompensation . The anterior palate has proven to be an advantageous region for insertion in conjunction with the correct mechanics . ZusammenfassungFragestellung : Bei ausgeprägten dentoalveolären Kompensationen einer skelettalen Klasse III ist i m Rahmen der prächirurgischen Dekompensation oftmals die Extraktion von Oberkiefer-Seitenzähnen mit Retraktion der Front indiziert . Die in diesem Rahmen gewünschte signifikante Vergrößerung der negativen sagittalen Frontzahnstufe erfordert oft eine maximale Verankerung der Oberkiefermolaren . Ziel dieser Studie war der Vergleich der Qualität der konventionellen und skelettalen Molarenverankerung mittels Mini-Implantaten i m Rahmen der präoperativen Dekompensation . Patienten und Method ik : Bei 20 Patienten mit einer ausgeprägten skelettalen Klasse III wurden zur präoperativen Dekompensation symmetrisch jeweils zwei Seitenzähne i m Oberkiefer extrahiert sowie eine Frontretraktion durchgeführt . Die Molarenverankerung erfolgte bei der einen Hälfte der Patienten jeweils mittels konventioneller Verankerung ( Transpalatinalbogen ) und bei der and eren Hälfte skelettal mittels Mini-Implantaten i m anterioren Gaumen . Vor und nach dem Lückenschluss wurden Studienmodelle angefertigt und mittels eines 3D-Scanners ( Ortho-Proof ) vermessen . Sowohl das beidseitige Ausmaß der Mesialw and erung der Molaren als auch eine Veränderung in der Transversalen wurden ausgewertet ( DigiModel Software).Ergebnisse : Bei allen Patienten kam es bei Belastung der Verankerungseinheit zu einer Mesialw and erung der Oberkiefermolaren . Bei konventioneller Verankerung war der Verankerungsverlust mit 4,21 mm ( ± 1,17 mm ) größer als bei skelettaler Verankerung i m anterioren Gaumen mit 2,05 mm ( ± 1,39 mm ) . Je nach Design und Stärke des Transpalatinalbogens zeigte sich eine Tendenz zur transversalen Erweiterung i m Molarenbereich . Schlussfolgerungen : Die skelettale Molarenverankerung zeigte eine höhere Effektivität als die konventionelle Verankerung . Insbesondere bei Patienten mit einem großen Bedarf an präoperativer Dekompensation sollte daher der skelettalen Verankerung der Vorzug gegeben werden . Der anteriore Gaumen erwies sich in Kombination mit einer geeigneten Mechanik für diese Aufgabe als vorteilhafte Insertionsregion The aim of this study was to evaluate and compare the dentofacial effects of 1 week rapid palatal expansion ( RPE ) and activation-deactivation ( A/D ) RPE protocol s with reverse headgear ( RH ) . Two groups , each containing 15 subjects , were included in this study . In the RPE group ( seven males and eight females , 11.94 ± 1.62 years ) , Hyrax screws were activated every 12 hours for 1 week . At the end of this period , RPE was stopped and the patients were instructed to wear the RH . In the A/D-RPE group ( seven males and eight females , 11.34 ± 1.81 years ) , the screws were activated every 12 hours for 1 week . Subsequently , the screws were deactivated every 12 hours for 1 week followed by activation and deactivation for the following 2 weeks . After this protocol , the patients were instructed to use the RH . A total force of 700 g was applied to both groups for 16 - 18 hours/day for the first 3 months , for 12 hours/day for the second 3 months , and for 6 hours/day for the second 6 months . Lateral cephalometric films were taken before treatment ( T1 ) and at the end of the first ( T2 ) and second ( T3 ) 6 months to evaluate the dentofacial changes . Intragroup differences of each l and mark at T2-T1 , T3-T2 , and T3-T1 were analysed with a paired t-test ( P < 0.016 ) , and intergroup differences were compared with an independent t-test ( P < 0.05 ) . Anterior movement of point A ( 4.13 mm ) for the A/D-RPE group was approximately twice of the RPE group ( 2.33 mm ; P < 0.001 ) . Backward movement of the m and ible showed no significant difference between the groups . Anterior face height increases did not demonstrate significant differences between the groups . The pronounced anterior movement of point A demonstrates that the A/D-RPE procedure positively affects maxillary protraction The aims of this study were to evaluate ( i ) the effect of ethnicity , social deprivation , and normative orthodontic treatment need on orthodontic aesthetic self-perception , self-perceived need for orthodontic treatment , and oral aesthetic impact of malocclusion ; ( ii ) the effect of ethnicity , social deprivation , and gender on perceived orthodontic treatment need and use of orthodontic services ; ( iii ) the influence of perceived oral aesthetic impact of malocclusion on perceived need and wish for orthodontic treatment ; and ( iv ) whether orthodontic treatment experience influences perceived oral aesthetic impact of malocclusion . A stratified , r and om sample of 434 14 - 15-year-old children from schools in Manchester , UK , was obtained . Information was collected on orthodontic aesthetic self-perception and orthodontic treatment experience using a question naire . The former data were combined to form an Oral Aesthetic Subjective Impact Scale ( OASIS ) . Normative orthodontic treatment need was measured with the Index of Orthodontic Treatment Need ( IOTN ) . Children with higher clinical need for orthodontic treatment perceived themselves as worse off than their peers with lower need . More socially deprived children or those with high IOTN aesthetic component ( AC ) scores had a higher ( i.e. more negative ) aesthetic impact ( OASIS ) score . Asians and females had higher IOTN dental health component ( DHC ) scores , but a better aesthetic appearance than Caucasians and males . More deprived children were less likely to have received orthodontic treatment . Despite this , OASIS scores were similar between treated and untreated children . Untreated children who wished for orthodontic treatment had higher IOTN AC and OASIS scores INTRODUCTION In this cephalometric investigation , we analyzed the treatment effects of bone-anchored maxillary protraction ( BAMP ) with miniplates in the maxilla and m and ible connected by Class III elastics in patients with Class III malocclusion . METHODS The treated sample consisted of 21 Class III patients consecutively treated with the BAMP protocol before the pubertal growth spurt ( mean age , 11.10 ± 1.8 years ) and reevaluated after BAMP therapy , about 1 year later . The treated group was compared with a matched control group of 18 untreated Class III subjects . Significant differences between the treated and control groups were assessed with independent- sample t tests ( P < 0.05 ) . RESULTS Sagittal measurements of the maxilla showed highly significant improvements during active treatment ( about 4 mm more than the untreated controls ) , with significant protraction effects at orbitale and pterygomaxillare . Significant improvements of overjet and molar relationship were recorded , as well as in the m and ibular skeletal measures at Point B and pogonion . Vertical skeletal changes and modifications in incisor Output:	There is some evidence that the use of a facemask to correct prominent lower front teeth in children is effective when compared to no treatment on a short-term basis .
MS21268	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Macrolide treatment has been reported to reduce the risk of recurrent ischaemic heart disease . The influence of a macrolide on the expansion rate of small abdominal aortic aneurysms ( AAA ) is unknown at present . The aim of this study was to investigate the effect of roxithromycin on the expansion rate of small AAA . MATERIAL S AND METHODS A total of 92 patients with a small AAA were recruited from two population s. One population consisted of 6.339 men aged 65 - 73 years who were offered participation in a mass screening programme for AAA at the local hospital . From this population 66 subjects were recruited . The remaining 26 were recruited from among 49 subjects diagnosed at interval screening for an initial aortic diameter between 25 mm and 29 mm . The patients were r and omized to receive either oral roxithromycin 300 mg once daily for 28 days or matching placebo , and followed for a mean of 1.5 years . RESULTS During the first year the mean annual expansion rate of AAA was reduced by 44 % in the macrolid group ( 1.56 mm/year ) compared to 2.80 mm/year after placebo ( p = 0.02 ) . During the second year the difference was only 5 % . Multiple linear regression analysis showed that roxithromycin treatment and initial AAA size were significantly related to AAA expansion when adjusted for smoking , diastolic blood pressure , and IgA level > or = 20 . The logistic regression analysis confirmed a significant difference in expansion rates above 2 mm annually between the intervention and placebo groups , OR = 0.09 ( 95 % CI : 0.01 - 0.83 ) . DISCUSSION In comparison to placebo , roxithromycin 300 mg daily for four weeks reduced the expansion rate of AAA BACKGROUND To study the propranolol treatment of small abdominal aortic aneurysms ( AAA ) concerning intention to treat , side effects , and inhibition of expansion . METHODS DESIGN Two-year lasting prospect i ve r and omised double-blinded intervention trial . SETTING Hospital-based mass screening for AAA with annual ambulatory control of small AAA . PARTICIPANTS Of 122 screening-diagnosed small AAA , 51 ( 42 % ) were excluded because of contraindications or present beta-blockage , and 17 refused participation . Thus , 54 ( 44.3 % ) were included . INTERVENTION Participants were r and omised to 40 mg propranolol twice a day or placebo . MEASURES The same observed was used to follow-up AAA-expansion , side effects , quality of life ( QL ) , branchial and ankle blood pressure ( ABI ) , and pulmonary function ( FEV1 and FVC ) . RESULTS Sixty percent in the propranolol group , and 25 % in the placebo group dropped out , mainly caused by dyspnoea in the propranolol group ( RR=1.74 , 95 % C.I. : 1.06 - 2.86 ) . Five ( 16.7 % ) died in the propranolol group , while 1 ( 4.2 % ) died in the placebo group ( RR=1.6 ( 1.02 - 2.51 ) ) . Furthermore , decreased pulmonary function , ABI , and QL was noticed in the propranolol group . Consequently , the trial was stopped after two years . Ninety-five percent of the measurements of the AAA were measured within 2 mm variation . If expansion was defined as above 2 mm annually , the relative risk of expansion in the placebo group was 1.17 ( 0.74 - 1.85 ) , and 2.44 ( 0.88 - 6.77 ) among the non-drop-outs . CONCLUSIONS Only 22 % of small screenings-diagnosed AAA were treatable with propranolol for two years . Consequently , only large scale studies are capable of showing potential minor inhibition of expansion by propranolol . However , whether such treatment ever becomes ethically acceptable is debatable Objectives — To assess the importance of the private costs incurred by patients when making a judgment on the economics of screening for abdominal aortic aneurysm ( AAA ) , and to explore the variation in such costs depending on screening location . Setting — A district general hospital and general practitioner surgeries . Methods — Four hundred and ninety nine consecutive subjects attending for AAA screening completed a question naire asking about travel arrangements for the journey to and from the clinic , the distance travelled , the time taken , the mode of transport , and any out-of-pocket expenses incurred . In addition , at the clinic each subject was asked what activities they had forgone in attending the clinic . Time was valued differently depending on whether work or leisure activities were forgone . The total private cost for each attender was calculated and comparison was made between attenders at hospital and at general practice . Results — A significantly greater proportion of subjects were accompanied when attending hospital than when attending general practitioner ( GP ) surgeries . Most attenders travelled by car , but the journey time was significantly longer for those visiting hospital . The expected total private cost associated with attendance for AAA screening was £ 5.47 . Attendance at GP surgeries had a lower private cost ( £ 4.21 ) than attendance at hospital ( £ 6.87 ) . Only 7·3 % of all men surveyed , and 6·5 % of all companions , would have been taking part in some form of paid occupation if they had not attended for screening . Conclusion — Despite the fact that most attenders for AAA screening will be retired , the associated private costs are appreciable and should be considered in assessing the economics of such screening programmes . The level of private costs varied depending on the location of screening : clinics held at GP practice s had lower private costs than those held at hospital Screening for abdominal aortic aneurysm ( AAA ) is commonly restricted to men . Recent studies have indicated a possible increase in deaths due to ruptured AAA in women , and a higher rate of rupture in women than in men . The present report details results from a r and omized controlled trial that assessed the effects of screening women for AAA BACKGROUND Opposing views have been published on the importance of ultrasound screening for abdominal aortic aneurysms . The Multicentre Aneurysm Screening Study was design ed to assess whether or not such screening is beneficial . METHODS A population -based sample of men ( n=67800 ) aged 65 - 74 years was enrolled , and each individual r and omly allocated to either receive an invitation for an abdominal ultrasound scan ( invited group , n=33839 ) or not ( control group , n=33961 ) . Men in whom abdominal aortic aneurysms ( > or =3 cm in diameter ) were detected were followed-up with repeat ultrasound scans for a mean of 4.1 years . Surgery was considered on specific criteria ( diameter > or = 5.5 cm , expansion > or = 1 cm per year , symptoms ) . Mortality data were obtained from the Office of National Statistics , and an intention-to-treat analysis was based on cause of death . Quality of life was assessed with four st and ardised scales . The primary outcome measure was mortality related to abdominal aortic aneurysm . FINDINGS 27147 of 33839 ( 80 % ) men in the invited group accepted the invitation to screening , and 1333 aneurysms were detected . There were 65 aneurysm-related deaths ( absolute risk 0.19 % ) in the invited group , and 113 ( 0.33 % ) in the control group ( risk reduction 42 % , 95 % CI 22 - 58 ; p=0.0002 ) , with a 53 % reduction ( 95 % CI 30 - 64 ) in those who attended screening . 30-day mortality was 6 % ( 24 of 414 ) after elective surgery for an aneurysm , and 37 % ( 30 of 81 ) after emergency surgery . INTERPRETATION Our results provide reliable evidence of benefit from screening for abdominal aortic aneurysms The study was an up date at 10 years of a r and omized trial of the efficacy of screening for abdominal aortic aneurysm ( AAA ) . The extent of benefit , feasibility and compliance were examined , and reasons why this intervention may fail a proportion of those screened were identified Macrolide treatment has been reported to lower the risk of recurrent ischaemic heart disease . The influence of macrolides on the expansion rate of abdominal aortic aneurysms ( AAAs ) remains unknown . The aim was to investigate the effect of roxithromycin on the expansion rate of small AAAs OBJECTIVE To investigate risk factors associated with aneurysm rupture using patients r and omized into the U.K. Small Aneurysm Trial ( n = 1090 ) or monitored for aneurysm growth in the associated study ( n = 1167 ) . SUMMARY BACKGROUND DATA The U.K. Small Aneurysm Trial has shown that ultrasound surveillance is a safe management option for patients with small abdominal aortic aneurysms ( 4.0 to 5.5 cm in diameter ) , with an annual rupture rate of 1 % . METHODS In the cohort of 2257 patients ( 79 % male ) , aged 59 to 77 years , 103 instances of abdominal aortic aneurysm rupture were identified during the 7-year period of follow-up ( 1991 - 1998 ) . Almost all patients ( 98 % ) had initial aneurysm diameters in the range of 3 to 6 cm , and the majority of ruptures ( 76 % ) occurred in patients with aneurysms > or = 5 cm in diameter . Kaplan-Meier survival and Cox regression analysis were used to identify baseline risk factors associated with aneurysm rupture . RESULTS After 3 years , the annual rate of aneurysm rupture was 2.2 % ( 95 % confidence interval 1.7 to 2.8 ) . The risk of rupture was independently and significantly associated with female sex ( p < 0.001 ) , larger initial aneurysm diameter ( p < 0.001 ) , lower FEV1 ( p = 0.004 ) , current smoking ( p = 0.01 ) , and higher mean blood pressure ( p = 0.01 ) . Age , body mass index , serum cholesterol concentration , and ankle/brachial pressure index were not associated with an increased risk of aneurysm rupture . CONCLUSIONS Within this cohort of patients , women had a threefold higher risk of aneurysm rupture than men . Effective control of blood pressure and cessation of smoking are likely to diminish the risk of rupture OBJECTIVES to analyse the hospital costs and benefits of screening older males for abdominal aortic aneurysm ( AAA ) . MATERIAL S AND METHODS in 1994 a hospital-based screening trial of 12 658 65 - 73-year-old males was started . AAA > 5 cm were referred for surgery . The remaining AAA were offered annual scans . Those with aortic ectasia were rescreened at 5 yearly intervals . AAA-operations and hospital AAA-related deaths were research ed . The costs of screening , surveillance , and treatment were also registered . RESULTS the attendance rate was 76 % ; of whom 191 ( 4.0 % ) had AAA . Mean observation time was 5.13 years . Sixty in the screened and 41 in the control group were operated ( p=0.06 ) , of which 7 and 27 respectively were operated as an emergency ( p<0.001 ) , and 6 and 19 respectively died due to AAA ( p=0.009 ) . The costs per scan were 83.50 DKK , 81 400 DKK per emergency operation ( 71 485 DKK after screening ) , and 117 000 DKK per emergency operation . The cost per prevented hospital death was 67 855 DKK , equivalent to approximately life year saved approx . 7540 DKK ( GBP1=12 DKK ) . CONCLUSION screening appears to reduce hospital AAA mortality and to be cost-effective OBJECTIVE To describe the potential psychological consequences of screening for abdominal aortic aneurysms ( AAAs ) . METHODS The participants were prospect ively and r and omly sample d from a r and omised screening trial for AAA and asked to complete a vali date d generic and global anonymous quality of life ( QL ) question naire by self- assessment ( ScreenQL ) . Material case-control study : ScreenQL was completed once by 168 ( 48 % ) of 350 non-responders to screening , 271 ( 81 % ) of 335 attenders before screening , 286 ( 85 % ) of 335 attenders after screening , 127 ( 85 % ) of 149 with a small AAA diagnosed at screening , and 231 ( 66 % ) of 350 who were r and omised not to be offered screening for AAA ( controls ) . Prospect i ve study ( paired data ): 127 men having a small AAA diagnosed . Twenty-nine ( 81 % ) of 36 men operated after initial conservative treatment . RESULTS Initially , the QL score was 5 % lower among men with a small AAA compared to the controls ( p<0.05 ) , mainly because of poorer health perception . The QL score declined significantly further to 7 % below control values during the period of conservative treatment . This impair Output:	AUTHORS ' CONCLUSIONS There is evidence of a significant reduction in mortality from AAA in men aged 65 to 79 years who undergo ultrasound screening . There is insufficient evidence to demonstrate benefit in women .
MS21269	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Exposure to cat and dog allergens is very common in the Western World and is a serious cause of asthma in sensitized subjects . OBJECTIVE We sought to study the clinical effects of air cleaners in living rooms and bedrooms of asthmatic children sensitized to cat or dog allergens . METHODS Twenty asthmatic children sensitized to pet allergens ( cat/dog ) and with an animal at home participated in a double-blind , placebo-controlled , cross-over study in which the effects of air cleaners placed in the living room and bedroom for 3 months were compared with the effects of sham air cleaners . Before and after each study period , lung function , airway hyperresponsiveness ( adenosine monophosphate ) , and peak flow variation were recorded . Cat and dog allergen levels were assessed in the filters of the air cleaners . RESULTS After a 3-month intervention with active air cleaners , airway hyperresponsiveness decreased significantly , showing a 1.2 doubling dose increase of PC(20 ) adenosine ( P = .003 ) . Peak flow amplitude also decreased ( P = . 045 ) . Substantial amounts of airborne cat and dog allergen were captured by the air cleaners in living rooms and bedrooms as well . Allergen levels in floor dust were not changed . CONCLUSION In young asthmatic patients sensitized and exposed to pets in the home , application of air cleaners in living rooms and bedrooms was accompanied by a significant improvement in airway hyperresponsiveness and a decrease in peak flow amplitude The effects of supplementary computer instruction in house dust mite-avoidance measures on adherence to implementing measures , on home dust mite-allergen levels , and on symptomatology were investigated in 52 adult patients with mite-associated asthma . Twenty-six patients received conventional instruction ( counseling and written instruction ) and the other 26 patients received conventional plus 22 minutes of interactive computer-assisted instruction . Instructions were aim ed at mite-avoidance measures . Pre- and postinstruction dust sample s were collected , and adherence was monitored . All patients kept symptom diaries twice a day . Patients ' progress was followed for 12 weeks , and all patients completed the study . Adherence , number of observed and self-reported mite-avoidance measures implemented after visit , was higher for the computer group ( p = 0.023 ) . The computer-instructed group achieved significantly lower levels of mite allergen in bedroom carpets ( p = 0.004 ) with mean levels of mite allergen declining from 6.5 + /- 7.6 to 2.2 + /- 4.3 micrograms/gm of dust ( two-site monoclonal antibody assays ) , whereas levels for the conventional-instructed group did not change . Moreover , by study weeks 9 and 10 , the computer-instructed group was significantly less symptomatic ( p = 0.033 ) . Mean symptom scores for this group decreased from 12.4 to 7.7 , compared with 16.4 to 14.3 . Conventional instruction supplemented with computer instruction is suggested in mite education To evaluate the effect of a room high-efficiency particulate air ( HEPA ) cleaner on cat-induced asthma and rhinitis , 35 cat-allergic subjects who were living with one or more cats were studied in a double-blind , placebo controlled trial . After a 1 mo baseline period , subjects ' bedrooms were equipped with an active or placebo air cleaner for the following 3 mo . Evaluations included monthly measurement of cat-allergen levels , daily morning , afternoon , and nighttime nasal- and chest-symptom scores , twice-daily measurement of peak-flow rates , daily medication scores , monthly spirometry , and methacholine ( MCh ) challenge testing before and after the study . Airborne allergen levels were reduced in the active-filter group as compared with the placebo group ( p = 0.045 ) . However , no differences were detected in settled-dust allergen levels ( p = 0.485 ) , morning , afternoon , or nighttime nasal-symptom scores ( p = 0.769 , 0.534 , and 0.138 ) , chest-symptom scores ( p = 0.388 , 0.179 , and 0.215 ) , sleep disturbance ( p = 0.101 ) , morning or afternoon peak-flow rates ( p = 0 . 424 and 0.679 ) , or rescue medication use ( nasal , p = 0.164 , chest , p = 0.650 ) , respectively . Although the combination of a HEPA room air cleaner , mattress and pillow covers , and cat exclusion from the bedroom did reduce airborne cat-allergen levels , no effect on disease activity was detected for any parameter studied BACKGROUND In Atlanta , as in other major urban areas of the United States , asthma is a leading cause of school absenteeism , emergency department use , and hospitalization . Recent guidelines for asthma management recommend reducing exposure to relevant allergens , but neither the feasibility nor the efficacy of this form of treatment has been established for children living in poverty . OBJECTIVE We sought to investigate allergen avoidance as a treatment for asthma among inner-city children . METHODS One hundred four children with asthma living in the city of Atlanta were enrolled into a controlled trial of avoidance without being skin tested . The children were r and omized to an active avoidance group , a placebo avoidance group , and a second control group for which no house visits occurred until the end of the first year . Avoidance included bed and pillow covers , hot washing of bedding , and cockroach bait . Eighty-five children completed the study , and the outcome was measured as unscheduled clinic visits , emergency department visits , and hospitalization for asthma , as well as changes in mite and cockroach allergen levels . RESULTS There was a significant decrease in acute visits for asthma among children whose homes were visited ( P < .001 ) . However , there was no significant difference between the active and placebo homes either in the effect on asthma visits or in allergen concentrations . When the children with mite allergy were considered separately , there was a significant correlation between decreased mite allergen and change in acute visits ( P < .01 ) . The avoidance measures for cockroach allergen appeared to be ineffective , and the changes observed did not correlate with changes in visits . CONCLUSIONS Applying allergen avoidance as a treatment for asthma among children living in poverty is difficult because of multiple sensitivities and problems applying the protocol s in this environment . The current results demonstrate that home visiting positively influences the management of asthma among families living in poverty . Furthermore , the results for children with mite allergy strongly suggest that decreasing relevant allergen exposure should be an objective of treatment in this population This study was design ed to assess the effectiveness of a high-efficiency particulate air ( HEPA ) filter in alleviating allergic respiratory symptoms . Thirty-two patients were studied who had symptomatic perennial rhinitis and /or asthma during the fall and winter months and had a positive skin test with house dust or house dust -- mite extract . An ENVIRACAIRE room air cleaner was placed in the bedroom for 8 weeks . In a r and om manner , the active filter was used for 4 weeks and a blank filter for 4 weeks . There was an average 70 % reduction in the particulate matter greater than or equal to 0.3 micron with the HEPA filter . In a double-blind design , results were assessed by analysis of the patients ' symptom/medication scores and subjective evaluation . For the total study , there was no difference in the total symptom/medication scores or individual symptom scores during the placebo and active-filter periods . Analysis of the last 2 weeks of each filter period in which respiratory infection was absent demonstrated definite differences in total and individual symptoms , suggesting active-filter benefit . Patients ' subjective responses also suggested benefit from the filter . The overall impression is that the HEPA filter can reduce allergic respiratory symptoms Recommendations for allergen avoidance or allergen reduction measures play an important part in the treatment of allergic asthmatic patients . The purpose of this study was to test recently developed air-cleaners with respect to their capacity to capture airborne allergen particles and to improve clinical parameters of asthmatic patients sensitized to aeroallergens . Forty five allergic asthmatic patients were studied in a double-blind procedure for 6 months . The patients were divided into three groups of 15 patients . In Group 1 , the intervention consisted of the application of active air-cleaners in living-rooms and bedrooms . In Group 2 , placebo air-cleaners were used in combination with allergen-impermeable mattress covers . In Group 3 , the same intervention was performed as in Group 2 but with active air-cleaners . Allergen levels in mattress and floor dust were measured before , and 3 and 6 months after the interventions . After 6 months , the air-cleaners were dismantled and the filters were analysed for the amount of dust collected and allergen content . Immunological and lung function parameters were measured before , and 3 and 6 months after the interventions . Considerable amounts of airborne dust and allergenic particles were captured in the filters of the air-cleaners . Up to the 18.9 g of dust , 4,513 ng of house dust mite allergen , Der p 1 , and 50,000 mU of cat allergen , Fel d 1 , ( in houses with cats ) were collected by air-cleaners in living-rooms . Only in Group 3 ( in which both active air-cleaners and mattress covers were used ) was a small ( less than 1 doubling dose ) but statistically significant improvement of provocative concentration of histamine causing a 20 % fall in forced expiratory volume in one second ( PC20 ) observed ( from 5.96 to 9.02 mg x mL(-1 ) ) . The amount of dust and house dust mite allergen collected in the filters was significantly correlated with an improvement of peak flow variation . In combination with other allergen avoidance measures , the examined air-cleaners can contribute to diminished allergen exposure and improvement of airway hyperresponsiveness in asthmatic patients A new , portable laminar air-flow filter ( Enviracaire ) was tested on 13 asthmatic children , using a double-blind single crossover study . There was a statistical improvement in symptom scores during filter use ; however , peak flows did not improve significantly . The authors feel this method of avoiding indoor airborne irritants is useful and warrants further study The efficacy of an air‐cleaning device equipped with a high efficiency particulate air ( HEPA ) filter ( without further avoidance measures ) was studied in patients allergic to house dust mite . The effects of the air‐cleaner on indoor Dermatophagoides sp. levels , symptom score and bronchial hyperresponsiveness in nine mite‐allergic patients were assessed using a cross‐over controlled study . No significant effect was demonstrated on indoor Dermatophagoides sp. levels when comparing the period of air‐cleaner activity ( 2 months ) with the control period ( 2 months ) . The Dermatophagoides sp. levels in the houses studied were lower than the risk level for asthmatic attacks , making it difficult to assess any effect on asthma ; however , neither bronchial hyperresponsiveness nor rhinitis symptom score were changed by air‐cleaner activity . During the trial period , however the mean level of Dermatophagoides sp. allergen in the houses changed spontaneously from 4.4 Hg/g ( mean level in the first 2 trial months ) to 1 . 75 μg/g of dust ( second 2 months ) ( P < 0.05 ) . Owing to this change , the mean rhinitis symptom score also decreased ( P < 0.05 ) , even if no significant correlation was demonstrated ( r = 0.4 P= 0.089 ) . HEPA filter air‐cleaners appear insufficient as substitutes for st and ard avoidance measures in mite allergic patients Output:	No significant differences were detected between active intervention and control on the primary and secondary outcome measures reported in the studies . There are no trials of other allergen reduction measures , such as pet washing or possibly pet removal
MS21270	*TASK* the task is to summarize an input biomedical literature in six sentences *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 . A prospect i ve r and omized controlled trial . Objectives . To examine the effectiveness of combined manipulative treatment , stabilizing exercises , and physician consultation compared with physician consultation alone for chronic low back pain . Summary of Background Data . Strong evidence exists that manual therapy provides more effective short-term pain relief than does placebo treatment in the management of chronic low back pain . The evidence for long-term effect is lacking . Methods . Two hundred four chronic low back pain patients , whose Oswestry disability index was at least 16 % , were r and omly assigned to either a manipulative-treatment group or a consultation group . All were clinical ly examined , informed about their back pain , provided with an educational booklet , and were given specific instructions based on the clinical evaluation . The treatment included four sessions of manipulation and stabilizing exercises aim ing to correct the lumbopelvic rhythm . Question naires inquired about pain intensity , self-rated disability , mental depression , health-related quality of life , health care costs , and production costs . Results . At the baseline , the groups were comparable , except for the percentage of employees ( P = 0.01 ) . At the 5- and 12-month follow-ups , the manipulative-treatment group showed more significant reductions in pain intensity ( P < 0.001 ) and in self-rated disability ( P = 0.002 ) than the consultation group . However , we detected no significant difference between the groups in health-related quality of life or in costs . Conclusions . The manipulative treatment with stabilizing exercises was more effective in reducing pain intensity and disability than the physician consultation alone . The present study showed that short , specific treatment programs with proper patient information may alter the course of chronic low back pain Objective : This article examines the effectiveness of manual therapy with specific adjuvant exercise for treating chronic low back pain and disability . Methods : A single blind , r and omized , controlled trial was employed . Patients were prescribed an exercise program that was tailored to treat their musculoskeletal dysfunctions or given a nonspecific program of general stretching and aerobic conditioning . In addition , patients received manual therapy or sham manual therapy . Participants were seen for 6 weekly sessions and were asked to perform their exercise program twice daily . Results : Seventy-two out of 100 patients completed the study . Multivariate tests conducted for measures of pain and disability revealed a significant group by time interaction ( P = 0.04 and P = 0.05 , respectively ) , indicating differential change in these measures pretreatment to posttreatment as a function of the treatment received . When controlling for pretreatment scores , patients receiving manual therapy with specific adjuvant exercise reported significant reductions in pain . No change in perceived disability was observed , with the exception that patients receiving sham manual therapy with specific adjuvant exercise reported significantly greater disability at posttreatment . Discussion : Manual therapy with specific adjuvant exercise appears to be beneficial in treating chronic low back pain . Despite changes in pain , perceived function did not improve . It is possible that impacting chronic low back pain alone does not address psychosocial or other factors that may contribute to disability . Further studies are needed to examine the long-term effects of these interventions and to address what adjuncts are beneficial in improving function in this population Abstract Practice guidelines recommend various types of exercise and manipulative therapy for chronic back pain but there have been few head‐to‐head comparisons of these interventions . We conducted a r and omized controlled trial to compare effects of general exercise , motor control exercise and manipulative therapy on function and perceived effect of intervention in patients with chronic back pain . Two hundred and forty adults with non‐specific low back pain ⩾3 months were allocated to groups that received 8 weeks of general exercise , motor control exercise or spinal manipulative therapy . General exercise included strengthening , stretching and aerobic exercises . Motor control exercise involved retraining specific trunk muscles using ultrasound feedback . Spinal manipulative therapy included joint mobilization and manipulation . Primary outcomes were patient‐specific function ( PSFS , 3–30 ) and global perceived effect ( GPE , −5 to 5 ) at 8 weeks . These outcomes were also measured at 6 and 12 months . Follow‐up was 93 % at 8 weeks and 88 % at 6 and 12 months . The motor control exercise group had slightly better outcomes than the general exercise group at 8 weeks ( between‐group difference : PSFS 2.9 , 95 % CI : 0.9–4.8 ; GPE 1.7 , 95 % CI : 0.9–2.4 ) , as did the spinal manipulative therapy group ( PSFS 2.3 , 95 % CI : 0.4–4.2 ; GPE 1.2 , 95 % CI : 0.4–2.0 ) . The groups had similar outcomes at 6 and 12 months . Motor control exercise and spinal manipulative therapy produce slightly better short‐term function and perceptions of effect than general exercise , but not better medium or long‐term effects , in patients with chronic non‐specific back pain BACKGROUND CONTEXT Several conservative therapies have been shown to be beneficial in the treatment of chronic low back pain ( CLBP ) , including different forms of exercise and spinal manipulative therapy ( SMT ) . The efficacy of less time-consuming and less costly self-care interventions , for example , home exercise , remains inconclusive in CLBP population s. PURPOSE The purpose of this study was to assess the relative efficacy of supervised exercise , spinal manipulation , and home exercise for the treatment of CLBP . STUDY DESIGN / SETTING An observer-blinded and mixed- method r and omized clinical trial conducted in a university research clinic in Bloomington , MN , USA . PATIENT SAMPLE Individuals , 18 to 65 years of age , who had a primary complaint of mechanical LBP of at least 6-week duration with or without radiating pain to the lower extremity were included in this trial . OUTCOME MEASURES Patient-rated outcomes were pain , disability , general health status , medication use , global improvement , and satisfaction . Trunk muscle endurance and strength were assessed by blinded examiners , and qualitative interviews were performed at the end of the 12-week treatment phase . METHODS This prospect i ve r and omized clinical trial examined the short- ( 12 weeks ) and long-term ( 52 weeks ) relative efficacy of high-dose , supervised low-tech trunk exercise , chiropractic SMT , and a short course of home exercise and self-care advice for the treatment of LBP of at least 6-week duration . The study was approved by local institutional review boards . RESULTS A total of 301 individuals were included in this trial . For all three treatment groups , outcomes improved during the 12 weeks of treatment . Those who received supervised trunk exercise were most satisfied with care and experienced the greatest gains in trunk muscle endurance and strength , but they did not significantly differ from those receiving chiropractic spinal manipulation or home exercise in terms of pain and other patient-rated individual outcomes , in both the short- and long-term . CONCLUSIONS For CLBP , supervised exercise was significantly better than chiropractic spinal manipulation and home exercise in terms of satisfaction with treatment and trunk muscle endurance and strength . Although the short- and long-term differences between groups in patient-rated pain , disability , improvement , general health status , and medication use consistently favored the supervised exercise group , the differences were relatively small and not statistically significant for these individual outcomes Study Design . R and omized , single blind , controlled trial . Objective . To determine the efficacy of 2 components of musculoskeletal physiotherapy on chronic low back disorder . Summary of Background Data . Musculoskeletal physiotherapy encompasses many treatment methods , however , manual therapy and exercises to rehabilitate spinal stabilization are the most frequently used . Despite their popularity , scant evidence supports their use on subjects with chronic low back disorder . Methods . A total of 346 subjects were r and omized to manual therapy , a 10-week spinal stabilization rehabilitation program , or a minimal intervention control group . Data were collected at baseline , and 3 , 6 , 12 , and 24 months after intervention . Outcome measures recorded intensity of low back pain , disability , h and icap , medication , and quality of life . There were 4 main variables combined in a primary component analysis to form a single outcome measure ( i.e. , a measure of dysfunction ) . Results . The results indicated statistically significant improvements in favor of the spinal stabilization group at the 6-month stage in pain ( 65.9 % reduction in symptoms ) and dysfunction ( combined mean reduction of 134 , st and ard error 23.84 ) , and at the 1-year stage in medication ( 34.3 % reduction in medication ) , dysfunction ( combined mean reduction of 134 , st and ard error 18.2 ) , and disability ( mean difference in change 15.71 Oswestry Disability Index , 95 % confidence interval 19.3–10.01 ) . Conclusions . As a component of musculoskeletal physiotherapy , the spinal stabilization program is more effective than manually applied therapy or an education booklet in treating chronic low back disorder over time . Both manual therapy and the spinal stabilization program are significantly effective in pain reduction in comparison to an active control . To our knowledge and up until now , this result has not been shown in patients with chronic low back disorder Background Recent clinical recommendations still propose active exercises ( AE ) for CNSLBP . However , acceptance of exercises by patients may be limited by pain-related manifestations . Current evidence s suggest that manual therapy ( MT ) induces an immediate analgesic effect through neurophysiologic mechanisms at peripheral , spinal and cortical levels . The aim of this pilot study was first , to assess whether MT has an immediate analgesic effect , and second , to compare the lasting effect on functional disability of MT plus AE to sham therapy ( ST ) plus AE . Methods Forty-two CNSLBP patients without co-morbidities , r and omly distributed into 2 treatment groups , received either spinal manipulation/mobilization ( first intervention ) plus AE ( MT group ; n = 22 ) , or detuned ultrasound ( first intervention ) plus AE ( ST group ; n = 20 ) . Eight therapeutic sessions were delivered over 4 to 8 weeks . Immediate analgesic effect was obtained by measuring pain intensity ( Visual Analogue Scale ) before and immediately after the first intervention of each therapeutic session . Pain intensity , disability ( Oswestry Disability Index ) , fear-avoidance beliefs ( Fear-Avoidance Beliefs Question naire ) , erector spinae and abdominal muscles endurance ( Sorensen and Shirado tests ) were assessed before treatment , after the 8th therapeutic session , and at 3- and 6-month follow-ups . Results Thirty-seven subjects completed the study . MT intervention induced a better immediate analgesic effect that was independent from the therapeutic session ( VAS mean difference between interventions : -0.8 ; 95 % CI : -1.2 to −0.3 ) . Independently from time after treatment , MT + AE induced lower disability ( ODI mean group difference : -7.1 ; 95 % CI : -12.8 to −1.5 ) and a trend to lower pain ( VAS mean group difference : -1.2 ; 95 % CI : -2.4 to −0.30 ) . Six months after treatment , Shirado test was better for the ST group ( Shirado mean group difference : -61.6 ; 95 % CI : -117.5 to −5.7 ) . Insufficient evidence for group differences was found in remaining outcomes . Conclusions This study confirmed the immediate analgesic effect of MT over ST . Followed by specific active exercises , it reduces significantly functional disability and tends to induce a larger decrease in pain intensity , compared to a control group . These results confirm the clinical relevance of MT as an appropriate treatment for CNSLBP . Its neurophysiologic mechanisms at cortical level should be investigated more thoroughly . Trial registration Trial registration number : OBJECTIVE To study the efficacy of manual therapy and physiotherapy in subgroups of patients with persistent back and neck complaints . The second objective was to determine the correlation between three important outcome measures used in this trial . DESIGN R and omized clinical trial ( subgroup analysis ) . SETTING Primary health care in the Netherl and s. PATIENTS Two hundred fifty-six patients with nonspecific back and neck complaints of at least 6 wk duration who had not received physiotherapy or manual therapy in the past 2 yr . INTERVENTIONS At the discretion of the manual therapists , physiotherapists and general practitioners . Physiotherapy consisted of exercises , massage and physical therapy ( heat , electrotherapy , ultrasound , shortwave diathermy ) . Manual therapy consisted of manipulation and mobilization of the spine . Treatment by the general practitioner consisted of drugs ( e.g. , analgesics ) , advice about posture , home exercises and (bed)rest . Placebo treatment consisted of detuned shortwave diathermy ( 10 min ) and detuned ultrasound ( 10 min ) . MAIN OUTCOME MEASURES Changes in severity of the main complaint and limitation of physical functioning measured on 10-point scales by a blinded research assistant and global perceived effect measured on a 6-point scale by the patients . RESULTS Improvement in the main complaint was larger with manual therapy ( 4.3 ) than with physiotherapy ( 2.5 ) for patients with chronic conditions ( duration complaint of 1 yr or longer ) . Also , improvement in the main complaint was larger with manual therapy ( 5.5 ) than with physiotherapy ( 4.0 ) for patients younger than 40 yr ( both were measured after 12-mo follow-up ) . Labeling of patients by the treating manual therapists as " suitable " or " not suitable " for treatment with manual therapy did not predict differences Output:	Based on the findings of this systematic review there is no conclusive evidence that clearly favours spinal manipulation or exercise as more effective in treatment of CLBP .
MS21271	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Home and supervised exercise programmes consisting of stretching and eccentric exercises have been recommended for the management of lateral elbow tendinopathy ( LET ) . No studies have examined their comparative efficacy effectiveness . Objective In this study , whether a home exercise programme is more successful than a supervised exercise programme in treating patients with LET was investigated . Methods Patients with unilateral LET for at least 4 weeks were included in this trial . They were sequentially allocated to receive either a home exercise programme or a supervised exercise programme five times a week for 12 weeks . The exercise programme consisted of slow progressive eccentric exercises of wrist extensors and static stretching of the extensor carpi radialis brevis tendon . Outcome measures were pain , using a visual analogue scale , and function , using a visual analogue scale and the pain-free grip strength . Patients were evaluated at baseline , at the end of treatment ( week 12 ) , and 3 months ( week 24 ) after the end of treatment . Results 70 patients met the inclusion criteria . At the end of treatment , there was a decline in pain and a rise in function in both groups compared with baseline ( p<0.0005 , paired t test ) . There were significant differences in the reduction of pain and the improvement of function between the groups at the end of treatment and at the 3-month follow up ; the supervised exercise programme produced the largest effect ( p<0.0005 , independent t test ) . Conclusions Supervised exercise programme is superior to home exercise programme to reduce pain and improve function in patients with LET at the end of the treatment and at the follow-up . Further research is needed to confirm our results Tendons adapt in response to sports-specific loading , but sometimes develop tendinopathy . If the presence of ultrasound changes like hypoechoic areas and neovascularization in asymptomatic tendons precede ( and predict ) future tendon problems is unknown . The aim of this prospect i ve cohort study was to investigate the relationship between the development of ultrasound changes in the patellar and quadriceps tendons and symptoms of jumper 's knee , as well to examine the medium-term effects of intensive training on tendon thickness among adolescent athletes . Elite junior volleyball athletes were followed with semi-annual ultrasound and clinical examinations ( average follow-up : 1.7 years ) . Of the 141 asymptomatic athletes included , 22 athletes ( 35 patellar tendons ) developed jumper 's knee . In a multivariate logistic regression analysis , a baseline finding of a hypoechoic tendon area ( odds ratio 3.3 , 95 % confidence interval 1.1 to 9.2 ) increased the risk of developing symptoms of jumper 's knee . Patellar tendon thickness among healthy athletes did not change ( Wilk 's lambda , P = 0.07 ) while quadriceps tendon thickness increased ( P = 0.001 ) . In conclusion , ultrasound changes at baseline were risk factors for developing symptoms of jumper 's knee . Also , among healthy athletes , we observed a 7 - 11 % increase in quadriceps tendon thickness , while there was no increase in patellar tendon thickness Background : Jumper ’s knee is a common and troublesome condition among senior volleyball players , but its prevalence among elite junior players compared to matched non-sports active controls is not known . Objective : To clinical ly , and by sonography , examine the patellar tendons in elite junior volleyball players ( 15–19 years ) at the Swedish National Centre for volleyball and in matched controls . Methods : The patellar tendons in the 57 students at the Swedish National Centre for high school volleyball and in 55 age , height , and weight matched not regularly sports active controls were evaluated clinical ly and by grey scale ultrasonography ( US ) and power Doppler ( PD ) sonography . Results : There were no significant differences in mean age , height , and weight between the volleyball players and the controls . In the volleyball group , jumper ’s knee was diagnosed clinical ly and by US in 12 patellar tendons ( 10 male and two female ) . In 12/12 tendons , PD sonography demonstrated a neovascularisation in the area with structural tendon changes . In another 10 pain free tendons , there were structural tendon changes and neovessels . In the control group , no individual had a clinical diagnosis of jumper ’s knee . US demonstrated structural tendon changes in 11 tendons , but there was no neovascularisation on PD sonography . Conclusions : A clinical diagnosis of jumper ’s knee , together with structural tendon changes and neovascularisation visualised with sonography , was seen among Swedish elite junior volleyball players but not in matched not regularly sports active controls . Structural tendon change alone was seen in 10 % of the control tendons Background : Jumper ’s knee patellar tendinopathy is well known to be a common and difficult injury in volleyball . Knowledge about its aetiology and pathogenesis is sparse . Objective : To prospect ively follow clinical status , tendon structure and vascularity in elite junior volleyball players . Methods : 22 volleyball players ( 44 patellar tendons ) beginning their first grade at the Swedish National Centre for high school volleyball were continuously evaluated clinical ly and by ultrasonography ( US ) and power Doppler ( PD ) over the 3 school years . Results : At inclusion , there were 44 tendons being assessed . Jumper ’s knee was diagnosed clinical ly in eight patellar tendons ( seven of eight had structural changes and vascularity on US+PD ) . There were 27 normal ( clinical and US+PD ) tendons . At 3 years , there were 36 tendons still being assessed . Four individuals ( eight tendons ) had been excluded . Jumper ’s knee had developed in 2 of 25 ( 2 were excluded ) tendons that were normal ( clinical and US+PD ) at inclusion . Jumper ’s knee ( clinical and US+PD ) was also present in six tendons . Conclusions : Normal clinical tests and ultrasound findings at the start indicated a low risk for these elite junior volleyball players to sustain jumper ’s knee during three school years with intensive training and playing Training volume and body composition have been suggested as risk factors for jumper 's knee among athletic youth , but research is lacking . The aim of this 4-year prospect i ve cohort study was to examine the relationship between training and competition load , body composition , and risk for developing jumper 's knee . Participants are elite volleyball players , aged 16 - 18 years . Training and competition load was recorded continuously and body composition semiannually . Jumper 's knee was diagnosed on a st and ardized clinical examination . We recruited 141 healthy students ( 69 males and 72 females ) , and 28 developed jumper 's knee ( 22 boys and six girls ) . In a multivariate analyses , boys had three to four times higher risk compared with girls . Volleyball training had an odds ratio ( OR ) 1.72 ( 1.18 - 2.53 ) for every extra hour trained , and match exposure was the strongest sports-related predictor for developing jumper 's knee with an OR of 3.88 ( 1.80 - 8.40 ) for every extra set played per week . We did not detect any significant differences between the groups in body composition at the time of inclusion or in the change of body composition during the study period . Conclusion , male gender , a high volume of volleyball training and match exposure were risk factors for developing jumper 's knee OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity Background : Patellar tendinopathy ( PT ) is one of the most common reasons for sport-induced pain of the knee . Low ankle dorsiflexion range might predispose for PT because of load-bearing compensation in the patellar tendon . Purpose : The purpose of this 1-year prospect i ve study was to analyze if a low ankle dorsiflexion range increases the risk of developing PT for basketball players . Study Design : Cohort study ( prognosis ) ; Level of evidence , 2 . Methods : Ninety junior elite basketball players were examined for different characteristics and potential risk factors for PT , including ankle dorsiflexion range in the dominant and nondominant leg . Data were collected over a 1-year period and follow-up , including reexamination , was made at the end of the year . Results : Seventy-five players met the inclusion criteria . At the follow-up , 12 players ( 16.0 % ) had developed unilateral PT . These players were found to have had a significantly lower mean ankle dorsiflexion range at baseline than the healthy players , with a mean difference of −4.7 ° ( P = .038 ) for the dominant limb and −5.1 ° ( P = .024 ) for the nondominant limb . Complementary statistical analysis showed that players with dorsiflexion range less than 36.5 ° had a risk of 18.5 % to 29.4 % of developing PT within a year , as compared with 1.8 % to 2.1 % for players with dorsiflexion range greater than 36.5 ° . Limbs with a history of 2 or more ankle sprains had a slightly less mean ankle dorsiflexion range compared to those with 0 or 1 sprain ( mean difference , −1.5 ° to −2.5 ° ) , although this was only statistically significant for nondominant legs . Conclusion : This study clearly shows that low ankle dorsiflexion range is a risk factor for developing PT in basketball players . In the studied material , an ankle dorsiflexion range of 36.5 ° was found to be the most appropriate cutoff point for prognostic screening . This might be useful information in identifying at-risk individuals in basketball teams and enabling preventive actions . A history of ankle sprains might contribute to reduced ankle dorsiflexion range Output:	This systematic review found that tendinopathy is present in children and adolescents , and increases in prevalence with age up to 18 years . Male sex is significantly associated with tendinopathy in studies that report tendinopathy by tendon
MS21272	*TASK* the task is to summarize an input biomedical literature in six sentences *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 volumetrically evaluate soft tissue changes of different ridge preservation techniques compared to spontaneous healing 6 months after tooth extraction . MATERIAL S AND METHODS In each of 40 patients , one single-rooted tooth was extracted and four treatment modalities were r and omly assigned to the following groups ( n = 10 each ) : A ) ß-tricalcium-phosphate-particles with a polylactid coating ( ß-TCP ) , B ) demineralized bovine bone mineral with 10 % collagen covered with a collagen matrix ( DBBM-C/CM ) , C ) DBBM with 10 % collagen covered with an autogenous soft tissue punch graft ( DBBM-C/PG ) , D ) spontaneous healing ( control ) . Impressions were obtained before extraction and 6 months later , casts were digitized and volumetric changes at the buccal soft tissues were determined . One-way anova was performed and pair-wise Wilcoxon rank sum test with Bonferroni-Holm method was applied for comparison of differences between two groups . RESULTS After 6 months , horizontal contour changes accounted for -1.7 ± 0.7 mm ( A ) , -1.2 ± 0.5 mm ( B ) , -1.2 ± 0.7 mm ( C ) and -1.8 ± 0.8 mm ( D ) . None of the group comparisons reached statistical significance . CONCLUSIONS Six months after tooth extraction all groups revealed a horizontal volume change in the buccal soft tissue contour . Application of DBBM-C/CM or DBBM-C/PG reduced the amount of volume resorption compared to ß-TCP or spontaneous healing without reaching statistically significant difference Aim To evaluate the effects of autologous platelet rich fibrin gel ( PRF gel ) on bone regeneration following extraction . Material s and Methods The study design was approved by the Institutional Ethical Committee . Study sample consisting of a total of 22 patients requiring bilateral transalveolar third molar extraction s were included after written informed consent . One side was r and omly chosen as case and the other side was the control . Autologous PRF gel was prepared from Fresh blood obtained from the patient . The PRF gel was placed in the extraction site and primary closure was obtained . The patient was called for a follow up on the first post op day , 1st week , one month , three month and six months post op . Regeneration of bone was measured using serial radiographs ( RVG ) at immediate post op , one , three and six months . This was then compared with the bone regeneration seen in the control group , with the radiographs taken at same intervals , to estimate the difference in bone regeneration if any . RVGs were assessed for amount of radiologic bone filling by the method described by Matteo Chiapasco et al. Results and Conclusion Higher mean pixels was recorded in cases compared to controls at all the time intervals viz . , immediate post op , 1 month post op , 3 months post op and 6 months post op . However , the difference in the mean pixels recorded between the two groups was not statistically significant ( P > 0.05 ) . For complete analysis , further follow up of the present patients and a larger sample size is required to obtain a conclusive result of the Bone Regeneration in extraction sockets with PRF gel This radiographic study evaluated the efficacy of different concentrations of rhBMP-2 to regenerate bone in alveolar defects in the anterior maxilla . The study was performed using reasonably st and ardized CT examinations and the Simplant program . The radiographic measurements were further refined by careful st and ardization of the measured regions of interest . There was a statistically significant difference in bone formation between subjects treated with a concentration of 1.5 mg/mL rhBMP-2 compared with each of the other groups . There was no statistically significant difference in bone volume between any of the other groups . None of the groups showed a loss in bone volume AIM To investigate the influence of the use L-PRF as a socket filling material and its ridge preservation properties . MATERIAL S AND METHODS Twenty-two patients in need of single bilateral and closely symmetrical tooth extraction s in the maxilla or m and ible were included in a split-mouth RCT . Treatments were r and omly assigned ( L-PRF socket filling versus natural healing ) . CBCT scans were obtained after tooth extraction and three months . Scans were evaluated by superimposition using the original DICOM data . Mean ridge width differences between timepoints were measured at three levels below the crest on both the buccal and lingual sides ( crest -1 mm ( primary outcome variable ) , -3 mm and -5 mm ) . RESULTS Mean vertical height changes at the buccal were -1.5 mm ( ±1.3 ) for control sites and 0.5 mm ( ±2.3 ) for test sites ( p < 0.005 ) . At the buccal side , control sites values were , respectively , -2.1 ( ±2.5 ) , -0.3 mm ( ±0.3 ) ( p < 0.005 ) and -0.1 mm ( ±0.0 ) , and test sites values were , respectively , -0.6 mm ( ±2.2 ) ( p < 0.005 ) , -0.1 mm ( ±0.3 ) and 0.0 mm ( ±0.1 ) . Significant differences ( p < 0.005 ) were found for total width reduction between test ( -22.84 % ) and control sites ( -51.92 % ) at 1 mm below crest level . Significant differences were found for socket fill ( visible mineralized bone ) between test ( 94.7 % ) and control sites ( 63.3 % ) . CONCLUSION The use of L-PRF as a socket filling material to achieve preservation of horizontal and vertical ridge dimension at three months after tooth extraction is beneficial BACKGROUND Reduction of alveolar height and width after tooth extraction may present problems for implant placement , especially in the anterior maxilla where bone volume is important for biologic and esthetic reasons . Different graft material s have been proposed to minimize the reduction in ridge volume . The aim of this study was to compare radiographic and histomorphometric results of magnesium-enriched hydroxyapatite ( MHA ) and calcium sulfate ( CS ) grafts in fresh sockets after tooth extraction s. METHODS Forty-five fresh extraction sockets with three bone walls were selected in 15 patients . A split-mouth design was used : 15 sockets on the right side of the jaw received MHA , 15 sockets on the left side received CS , and 15 r and om unfilled sockets were considered the control ( C ) group . Intraoral digital radiographs were taken at baseline and at 3 months after graft material placement . At 3 months , cylinder bone sample s were obtained for histology and histomorphometry analysis . RESULTS The difference in mean radiographic vertical bone level from baseline to 3 months was -2.48 + /- 0.65 mm in the CS group , -0.48 + /- 0.21 mm in the MHA group , and -3.75 + /- 0.63 mm in the unfilled C group . Statistically significant differences ( P < 0.05 ) were found between CS and MHA groups and between MHA and C groups . Histologic examination revealed bone formation in all treated sites ; trabecular bone assessment did not differ among apical , mesial , and coronal portions of the specimens . Mean vital bone measurements for CS , MHA , and C groups were 45.0 % + /- 6.5 % , 40.0 % + /- 2.7 % , and 32.8 % + /- 5.8 % , respectively . Statistically significant differences ( P < 0.05 ) were found among all groups . Connective tissue percentages averaged 41.5 % + /- 6.7 % for the CS group , 41.3 % + /- 1.3 % for the MHA group , and 64.6 % + /- 6.8 % for the C group . Statistically significant differences ( P < 0.05 ) were found between CS and C groups and between MHA and C groups . The CS-grafted sockets showed 13.9 % + /- 3.4 % residual implant material , whereas the MHA-treated sockets showed 20.2 % + /- 3.2 % residual material . The difference between the groups was statistically significant ( P < 0.05 ) . CONCLUSIONS Radiographs revealed a greater reduction of alveolar ridge in the CS group than in the MHA group . Histologic examination showed more bone formation and faster resorption in the CS group and more residual implant material in the MHA group Background and Purpose : The resorption of alveolar bone following tooth extraction results in a narrowing and shortening of the residual ridge , which leads to esthetic and restorative problems , and reduces the bone volume available for implant therapy . The aim of this study was to evaluate the prevention of alveolar collapse after tooth extraction , using titanium membrane ( Frios Boneshield ; DENTSPLY Friadent , Mannheim , Germany ) , associated ( or not ) with autologous bone graft . Material s and Methods : A total of 10 nonsmoking healthy subjects , ranging from 35 to 60 years old , were selected for this study . Each patient had a minimum of 2 uni-radicular periodontally hopeless teeth , which were scheduled for extraction . After the procedure , 2 titanium pins were fixed on the vestibular bone surfaces that were used as references for the initial measures ( depth , width , and height ) of the socket . Of the sockets,1 was r and omly chosen to be filled with autologous bone graft ( test ) removed from superior maxillary tuber , and the other one did not receive the graft ( control ) . A titanium membrane was adapted and fixed , covering the sockets , which remained for at least 10 weeks . After a 6-month healing , the final measures were performed . Results : There was exposure of the membrane in 5 of the 10 treated subjects . Average bone filling ( ±st and ard deviation ) among the 10 subjects was 8.80 ± 2.93 mm ( range 4 - 13 ) in the control group and 8.40 ± 3.35 mm ( range 4 - 13 ) in the test group . Average bone loss in width in both group was 1.40 ± 1.97 mm ( range −4 - 1 ) in the control group and 1.40 ± 0.98 mm ( range −4 - 0 ) in the test group . There was no significant statistical difference between groups considering the evaluated st and ards . Conclusion : The use of titanium membrane , alone or in association with autogenous bone , favored the prevention of alveolar ridge after tooth extraction . This membrane seems to be a possible and safe alternative to other nonresorbable membranes when the prevention of alveolar ridge resorption is the objective BACKGROUND The placement of different graft material s and /or the use of occlusive membranes to cover the extraction socket entrance are techniques aim ed at preserving/reducing alveolar ridge resorption . The use of grafting material s in fresh extraction sockets has , however , been question ed because particles of the grafted material have been found in alveolar sockets 6 - 9 months following their insertion . AIM The aims of the study were to ( i ) . evaluate whether alveolar ridge resorption following tooth extraction could be prevented or reduced by the application of a bioabsorbable polylactide-polyglycolide sponge used as a space filler , compared to natural healing by clot formation , and ( ii ) . evaluate histologically the amount and quality of bone tissue formed in the sockets , 6 months after the use of the bioabsorbable material . MATERIAL AND METHODS Thirty-six patients , undergoing periodontal therapy , participated in this study . All patients were scheduled for extraction of one or more compromised teeth . Following elevation of full-thickness flaps and extraction of teeth , measurements were taken to evaluate the distance between three l and marks ( mesio-buccal , mid-buccal , disto-buccal ) on individually prefabricated stents , and the alveolar crest . Twenty-six alveolar sockets ( test ) were filled with a bioabsorbable polylactide-polyglycolide acid sponge ( Fisiograft ) , while 13 sockets ( controls ) were allowed to heal without any filling material . The flaps were sutured with no attempt to achieve primary closure of the surgical wound . Re-entry for implant surgery was performed 6 months following the extraction s. Thirteen biopsies ( 10 test and three control sites ) were harvested from the sites scheduled for implant placement . RESULTS The clinical measurements at 6 months revealed , in the mesial-buccal site , a loss of bone height of 0.2 mm ( 1.4 SD ) in the test and 0.6 mm ( 1.1 SD ) in the controls ; in the mid-buccal portion a gain of 1.3 mm ( 1.9 SD ) in the test and a loss of 0.8 mm ( 1.6 SD ) in the controls ; and in the distal portion a loss of 0.1 mm ( 1.1 SD ) in the test and of 0.8 ( 1.5 SD ) mm in the controls . The biopsies harvested from the test sites revealed that the new bone formed at 6 months was mineralized , mature and well structured . Particles of the grafted material could not be identified in any of the 10 test biopsies . The bone formed in the control sites was also mature and well structured . CONCLUSION The results of this study indicate that alveolar bone resorption following tooth extraction may be prevented or reduced by the use of a bioabsorbable synthetic sponge of polylactide-polyglycolide acid . The quality of bone formed seemed to be optimal for dental implant insertion INTRODUCTION The closure of post extraction Output:	Alveolar ridge preservation procedures are effective in minimizing post extraction hard tissue dimensional loss . The outcomes of these procedures are affected by morphology of extraction sockets , type of wound closure , type of grafting material s , use of barrier membranes , and use of growth factors
MS21273	*TASK* the task is to summarize an input biomedical literature in six sentences *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 intensive efforts over many years , the United States has made limited progress in improving rates of survival from out-of-hospital cardiac arrest . Recently , national organizations , such as the American Heart Association , have focused on promoting byst and er cardiopulmonary resuscitation , use of automated external defibrillators , and other performance improvement efforts . Methods and Results — Using the Cardiac Arrest Registry to Enhance Survival ( CARES ) , a prospect i ve clinical registry , we identified 70 027 U.S. patients who experienced an out-of-hospital cardiac arrest between October 2005 and December 2012 . Using multilevel Poisson regression , we examined temporal trends in risk-adjusted survival . After adjusting for patient and cardiac arrest characteristics , risk-adjusted rates of out-of-hospital cardiac arrest survival increased from 5.7 % in the reference period of 2005 to 2006 to 7.2 % in 2008 ( adjusted risk ratio , 1.27 ; 95 % confidence interval , 1.12–1.43 ; P<0.001 ) . Survival improved more modestly to 8.3 % in 2012 ( adjusted risk ratio , 1.47 ; 95 % confidence interval , 1.26–1.70 ; P<0.001 ) . This improvement in survival occurred in both shockable and nonshockable arrest rhythms ( P for interaction=0.22 ) and was also accompanied by better neurological outcomes among survivors ( P for trend=0.01 ) . Improved survival was attributable to both higher rates of prehospital survival , where risk-adjusted rates increased from 14.3 % in 2005 to 2006 to 20.8 % in 2012 ( P for trend<0.001 ) , and in-hospital survival ( P for trend=0.015 ) . Rates of byst and er cardiopulmonary resuscitation and automated external defibrillator use modestly increased during the study period and partly accounted for prehospital survival trends . Conclusions — Data drawn from a large subset of U.S communities suggest that rates of survival from out-of-hospital cardiac arrest have improved among sites participating in a performance improvement registry BACKGROUND Timing of coronary angiography ( CAG ) is still controversial in the out-of-hospital cardiac arrest survivors who present without ST-segment elevation . METHODS AND RESULTS We analysed a prospect i ve registry of 158 comatose survivors of out-of-hospital cardiac arrest . For further analysis , we included 99 patients without ST-segment elevation on the initial electrocardiogram . All patients underwent temperature management . Urgent CAG ( < 2h from admission ) was performed in 25 % of the patients . A definite cause of the cardiac arrest could be identified during the index hospitalization in 82 patients : 36 had a non-ST-segment elevation acute coronary syndrome ( NSTE-ACS ) and 46 had a non-ACS diagnosis . Eighty-seven patients ( 88 % ) survived the index hospitalization and 65 ( 66 % ) were alive at six months . A favourable neurological status ( cerebral performance category ≤ 2 ) was observed in 56 % of the patients at discharge and in 56 % after six months of follow-up . Neither the survival nor the neurological outcome differed between the patients in whom the CAG was performed urgently upon the admission and the patients in whom the CAG was initially not performed , regardless of the aetiology of the cardiac arrest . On the other h and , performing an urgent CAG was safe and it did not prolong the average time to achieve an effective hypothermia . CONCLUSIONS Performing an urgent CAG in comatose cardiac arrest survivors without ST-segment elevation was not associated with better clinical and neurological outcome as compared to the initially conservative approach Purpose To investigate whether early coronary angiography ( CAG ) after out-of-hospital cardiac arrest of a presumed cardiac cause is associated with improved outcomes in patients without acute ST elevation . Methods The target temperature management after out-of-hospital cardiac arrest ( TTM ) trial showed no difference in all-cause mortality or neurological outcome between an intervention of 33 and 36 ° C . In this post hoc analysis , 544 patients where the admission electrocardiogram did not show acute ST elevation were included . Early CAG was defined as being performed on admission or within the first 6 h after arrest . Primary outcome was mortality at the end of trial . A Cox proportional hazard model was created to estimate hazard of death , adjusting for covariates . In addition , a propensity score matched analysis was performed . Results A total of 252 patients ( 46 % ) received early CAG , whereas 292 ( 54 % ) did not . At the end of the trial , 122 of 252 patients who received an early CAG ( 48 % ) and 159 of 292 patients who did not ( 54 % ) had died . The adjusted hazard ratio for death was 1.03 in the group that received an early CAG ; 95 % CI 0.80–1.32 , p = 0.82 . In the propensity score analysis early CAG was not significantly associated with survival . Conclusions In this post hoc observational study of a large r and omized trial , early coronary angiography for patients without acute ST elevation after out-of-hospital cardiac arrest of a presumed cardiac cause was not associated with improved survival . A r and omized trial is warranted to guide clinical practice AIM OF THE STUDY To question the beneficial effects of the recommended early percutaneous coronary intervention ( PCI ) after out-of-hospital cardiac arrest on 30-day survival with favourable neurological outcome . METHODS Prospect ively collected data of 1277 out of hospital cardiac arrest patients between 2005 and 2010 from a registry at a tertiary care university hospital were used for a cohort study . RESULTS In 494 ( 39 % ) arrest patients ST-segment elevation was identified in 249 ( 19 % ) . Within 12h after restoration of spontaneous circulation catheter laboratory investigations were initiated in 197 ( 79 % ) and PCI in 183 ( 93 % ) ( 78 % got PCI in less than 180 min ) . Adjustment for a cumulative time without chest compressions < 2 min , initial shockable rhythm , cardiac arrest witnessed by healthcare professionals , and a higher core temperature at time of hospitalization reduced the effect of PCI on favourable neurological outcome at 30 days ( OR 1.40 ; 95 % CI , 0.53 - 3.7 ) compared to the univariate analysis ( OR 2.52 ; 95 % CI , 1.42 - 4.48 ) . CONCLUSION This cohort study failed to demonstrate the beneficial effects of PCI as part of post-resuscitation care on 30-day survival with a favourable neurological outcome Background : Aggressive post-resuscitation care , in particular combining mild therapeutic hypothermia ( MTH ) with early coronary angiography ( CAG ) and percutaneous coronary intervention ( PCI ) , may improve prognosis after out-of-hospital cardiac arrest ( OHCA ) . Objectives : The study aims to assess the value of immediate CAG or PCI in comatose survivors after OHCA treated with MTH and their association with outcomes . Methods : Observational , prospect i ve analysis of all comatose , resuscitated patients treated with MTH at a tertiary centre and undergoing CAG or PCI ≤6 hours after OHCA , or non-invasively managed . Primary outcomes were 30-day and 1-year survival . Results : From March 2004–December 2012 , 141 ( 51 % ) out of 278 comatose patients after cardiac OHCA were treated with MTH ( median age : 64.5 ( interquartile range 55–73 ) years , males : 67 % , first shockable rhythm : 70 % , witnessed OHCA : 94 % , interval OHCA-resuscitation≤20 min : 81 % ) . Ninety-seven patients ( 69 % ) underwent early CAG , and 45 ( 32 % ) of them PCI . Patients undergoing CAG or PCI had a more favourable risk profile than subjects non-invasively managed . PCI treated patients had more bleedings , but no stent thrombosis occurred . Thirty-day and one-year unadjusted total mortality rates were 50 % and 72 % for non-invasively managed patients , 26 % and 38.7 % for patients su bmi tted only to CAG and 32 % and 36.6 % for patients treated with PCI ( p=0.0435 for early death , and p<0.0001 for one-year mortality , respectively ) . However , a propensity-matched score analysis did not confirm the survival advantage of invasive management ( p=0.093 ) . At multivariable analysis , clinical and OHCA-related variables as well as CAG , but not PCI , were associated with outcomes . Conclusions : Comatose patients cooled after OHCA and su bmi tted to emergency CAG or PCI are a favourable outcome population that receives optimal post-arrest care AIM OF STUDY Favourable hospital survival increased from 26 % to 56 % in the implementation phase of a new st and ard operating procedure ( SOP ) for treatment after out-of hospital cardiac arrest ( OHCA ) in 2003 . We now evaluate protocol adherence and survival rates after five years with this established SOP . METHODS This observational study is based on prospect ively collected registry data from all OHCA patients with cardiac aetiology admitted with spontaneous circulation to Ulleval Hospital between September 2003 and January 2009 . Three patient categories are described based on early assessment in the emergency department : conscious , comatose , and comatose patients receiving only palliative care , with main focus on comatose patients receiving active treatment . RESULTS Of 248 patients , 22 % were consciousness on admission , 70 % were comatose and received active treatment , while 8 % received only palliative care . Favourable survival from admittance to discharge remained at 56 % throughout the study period . Among actively treated patients 83 % received emergency coronary angiography and 48 % underwent subsequent percutaneous coronary intervention . In this cohort 63 % had an acute myocardial infa rct ion , ten of whom did not receive emergency coronary angiography . Among actively treated comatose patients , 6 % survived with unfavourable neurology , while 51 % of the deaths followed treatment withdrawal after prognostication of severe brain injury . CONCLUSION The previously reported doubling in survival rate remained throughout a five-year study period . Establishing reliable indication for emergency coronary angiography and interventions and validating prognostication rules in the hypothermia era are important challenges for future studies AIM To determine if early cardiac catheterization ( CC ) is associated with improved survival in comatose patients who are resuscitated after cardiac arrest when electrocardiographic evidence of ST-elevation myocardial infa rct ion ( STEMI ) is absent . METHODS We conducted a retrospective observational study of a prospect i ve cohort of 754 consecutive comatose patients treated with therapeutic hypothermia ( TH ) following cardiac arrest . RESULTS A total of 269 ( 35.7 % ) patients had cardiac arrest due to a ventricular arrhythmia without STEMI and were treated with TH . Of these , 122 ( 45.4 % ) received CC while comatose ( early CC ) . Acute coronary occlusion was discovered in 26.6 % of patients treated with early CC compared to 29.3 % of patients treated with late CC ( p=0.381 ) . Patients treated with early CC were more likely to survive to hospital discharge compared to those not treated with CC ( 65.6 % vs. 48.6 % ; p=0.017 ) . In a multivariate regression model that included study site , age , byst and er CPR , shock on admission , comorbid medical conditions , witnessed arrest , and time to return of spontaneous circulation , early CC was independently associated with a significant reduction in the risk of death ( OR 0.35 , 95 % CI 0.18 - 0.70 , p=0.003 ) . CONCLUSIONS In comatose survivors of cardiac arrest without STEMI who are treated with TH , early CC is associated with significantly decreased mortality . The incidence of acute coronary occlusion is high , even when STEMI is not present on the postresuscitation electrocardiogram Background —Whether to perform or not an immediate percutaneous coronary intervention ( PCI ) after out-of-hospital cardiac arrest is still debated . We aim ed to evaluate the impact of PCI on short- and long-term survival in out-of-hospital cardiac arrest patients admitted after successful resuscitation . Methods and Results —Between 2000 and 2013 , all nontrauma out-of-hospital cardiac arrest patients admitted in a Parisian cardiac arrest center after return of spontaneous circulation were prospect ively included . The association between immediate PCI and short- and long-term mortality was analyzed using logistic regression and Cox multivariate analysis , respectively . Propensity score-matching method was used to assess the influence of PCI on short- and long-term survival . During the study period , 1722 patients ( 7 Output:	Conclusion Among patients resuscitated from OHCA , early coronary angiography is associated with increased survival to discharge and favourable neurological outcome
MS21274	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: We developed a computer-stored medical record system containing a limited set of the total clinical data base -- primarily diagnostic studies and treatments . This system responds to its own content according to physician-authored reminder rules . To determine the effect of the reminder messages generated by 1490 rules on physician behavior , we r and omly assigned practitioners in a general medicine clinic to study or control groups . The computer found indications for six different actions per patient in 12 467 patients during a 2-year study : 61 study group residents who received computer reminders responded to 49 % of these indications ; 54 control group residents , to only 29 % ( p less than 0.0001 ) . Preventive care ( occult blood testing , mammographic screening , weight reduction diets , influenza and pneumococcal vaccines ) was affected . The intentions of the study group to use a given action for an indication predicted their response to the indications ( p less than 0.03 , r2 = 0.33 ) . The intentions of the control residents did not OBJECTIVE Compare weight loss and maintenance between a face-to-face ( FTF ) weight management clinic and a clinic delivered via virtual reality ( VR ) . METHODS Participants were r and omized to 3 months of weight loss with a weekly clinic delivered via FTF or VR and then 6 months ' weight maintenance delivered with VR . Data were collected at baseline and 3 and 6 months for weight and process variables . Twenty overweight and obese individuals ( 31.1 ± 3.6 years of age ; body mass index , 32.8 ± 5.1 ; 85 % females ; 20 % minorities ) responded to advertisement and met inclusion criteria . Diets ( 1,200 - 1,800 kcal/d ) used prepackaged meals , fruits and vegetables , and physical activity ( 300 min/wk ) . RESULTS Weight loss was significantly greater for FTF at 10.8 % compared with 7.6 % for VR ( P < .05 ) . However , weight maintenance was significantly greater for VR at 14.0 % compared with 9.5 % for FTF ( P < .05 ) . CONCLUSIONS AND IMPLICATION S Virtual reality compares favorably with FTF for weight loss and may facilitate greater weight maintenance OBJECTIVE To compare two strategies for childhood obesity management : ambulatory assistance ( individual ) and educational program ( in group ) . METHOD Children and adolescents from 7 to 13 years of age were selected at r and om . They were divided into two groups : individually assisted or assisted in groups . An educational program about childhood obesity was created , with monthly meetings that consisted of lectures with parents ' participation and group work . Simultaneously , children and teenagers of the other group received individual ambulatory assistance . The program took place for six months . Body composition , eating habits and physical activities were assessed before and after interventions . RESULTS The sample comprised 38 children and adolescents whose mean age was 9.9 years . The program was more effective in increasing physical activity ( p = 0.003 ) , specially walking ( p = 0.003 ) , as well as in reducing total cholesterol ( p = 0.038 ) . Reduction of body mass index , obesity index and caloric intake was similar in both groups . As for food habits , ambulatory assistance increased the intake of fruits ( p = 0.033 ) and vegetables ( p = 0.002 ) and reduced the amount of French fries and crisps ( p = 0.041 ) , while children participating in the program reduced the intake of soft drinks ( p = 0.022 ) , s and wiches , pizza and fast food ( p = 0.006 ) . CONCLUSIONS Both strategies for h and ling childhood obesity were favorable to changes in food and physical activity habits . Group assistance was as effective as individual assistance , consolidating it as an alternative for obesity treatment Objectives To test the impact of provider performance pay for anaemia reduction in rural China . Design A cluster r and omised trial of information , subsidies , and incentives for school principals to reduce anaemia among their students . Enumerators and study participants were not informed of study arm assignment . Setting 72 r and omly selected rural primary schools across northwest China . Participants 3553 fourth and fifth grade students aged 9 - 11 years . All fourth and fifth grade students in sample schools participated in the study . Interventions Sample schools were r and omly assigned to a control group , with no intervention , or one of three treatment arms : ( a ) an information arm , in which principals received information about anaemia ; ( b ) a subsidy arm , in which principals received information and unconditional subsidies ; and ( c ) an incentive arm , in which principals received information , subsidies , and financial incentives for reducing anaemia among students . Twenty seven schools were assigned to the control arm ( 1816 students at baseline , 1623 at end point ) , 15 were assigned to the information arm ( 659 students at baseline , 596 at end point ) , 15 to the subsidy arm ( 726 students at baseline , 667 at end point ) , and 15 to the incentive arm ( 743 students at baseline , 667 at end point ) . Main outcome measures Student haemoglobin concentrations . Results Mean student haemoglobin concentration rose by 1.5 g/L ( 95 % CI –1.1 to 4.1 ) in information schools , 0.8 g/L ( –1.8 to 3.3 ) in subsidy schools , and 2.4 g/L ( 0 to 4.9 ) in incentive schools compared with the control group . This increase in haemoglobin corresponded to a reduction in prevalence of anaemia ( Hb < 115 g/L ) of 24 % in incentive schools . Interactions with pre-existing incentives for principals to achieve good academic performance led to substantially larger gains in the information and incentive arms : when combined with incentives for good academic performance , associated effects on student haemoglobin concentration were 9.8 g/L ( 4.1 to 15.5 ) larger in information schools and 8.6 g/L ( 2.1 to 15.1 ) larger in incentive schools . Conclusions Financial incentives for health improvement were modestly effective . Underst and ing interactions with other motives and pre-existing incentives is critical . Trial registration number IS RCT N76158086 Background : Primary care providers often fail to identify patients who are overweight or obese or discuss weight management with them . Electronic health record-based tools may help providers with the assessment and management of overweight and obesity . Purpose : We describe the design of a trial to examine the effectiveness of electronic health record-based tools for the assessment and management of overweight and obesity among adult primary care patients , as well as the challenges we encountered . Methods : We developed several new features within the electronic health record used by primary care practice s affiliated with Brigham and Women ’s Hospital in Boston , MA . These features included ( 1 ) reminders to measure height and weight , ( 2 ) an alert asking providers to add overweight or obesity to the problem list , ( 3 ) reminders with tailored management recommendations , and ( 4 ) a Weight Management screen . We then conducted a pragmatic , cluster-r and omized controlled trial in 12 primary care practice s. Results : We r and omized 23 clinical teams ( “ clinics ” ) within the practice s to the intervention group ( n = 11 ) or the control group ( n = 12 ) . The new features were activated only for clinics in the intervention group . The intervention was implemented in two phases : the height and weight reminders went live on 15 December 2011 ( Phase 1 ) , and all of the other features went live on 11 June 2012 ( Phase 2 ) . Study enrollment went from December 2011 through December 2012 , and follow-up ended in December 2013 . The primary outcomes were 6-month and 12-month weight change among adult patients with body mass index ≥25 who had a visit at one of the primary care clinics during Phase 2 . Secondary outcome measures included the proportion of patients with a recorded body mass index in the electronic health record , the proportion of patients with body mass index ≥25 who had a diagnosis of overweight or obesity on the electronic health record problem list , and the proportion of patients with body mass index ≥25 who had a follow-up appointment about their weight or were prescribed weight loss medication . Lessons learned : We encountered challenges in our development of an intervention within the existing structure of an electronic health record . For example , although we decided to r and omize clinics within primary care practice s , this decision may have introduced contamination and led to some imbalance of patient characteristics between the intervention and control practice s. Using the electronic health record as the primary data source reduced the cost of the study , but not all desired data were recorded for every participant . Conclusion : Despite the challenges , this study should provide valuable information about the effectiveness of electronic health record-based tools for addressing overweight and obesity in primary care Abstract Objective To evaluate a training programme intended to improve the management of obesity , delivered to general practice teams . Design Cluster r and omised trial . Setting Northern and Yorkshire region of Engl and Participants 44 general practice s invited consecutively attending obese adults to participate ; 843 patients attended for collection of baseline data and were subsequently r and omised . Intervention 4.5 hour training programme promoting an obesity management model . Main outcome measures Difference in weight between patients in intervention and control groups at 12 months ( main outcome measure ) and at 3 months and 18 months ; change in practitioners ' knowledge and behaviour in obesity management consultations . Results Twelve months after training the patients in the intervention group were 1 ( 95 % confidence interval - 1.9 to 3.9 ) kg heavier than controls ( P = 0.5 ) . Some evidence indicated that practitioners ' knowledge had improved . Some aspects of the management model , including recording weight , target weight , and dietary targets , occurred more frequently in intervention practice s after the training , but in absolute terms levels of implementation were low . Conclusion A training package promoting a brief , prescriptive approach to the treatment of obesity through lifestyle modification , intended to be incorporated into routine clinical practice , did not ultimately affect the weight of this motivated and at risk cohort of patients BACKGROUND Healthcare costs attributable to obesity have previously involved estimations based on costs of diseases commonly considered as having obesity as an underlying factor . AIM To quantify the impact of obesity on total primary care drug prescribing . DESIGN OF STUDY Review of computer generated and h and written prescriptions to determine total prescribing volume for all drug classes . SETTING Twenty-three general practice surgeries in the UK . METHOD Stratified r and om selection of 1150 patients who were obese ( body mass index [ BMI ] > 30 kg/m(2 ) ) and 1150 age and sex-matched controls of normal weight ( BMI 18.5-<25 kg/m(2 ) ) . Retrospective review of medical records over an 18-month period . RESULTS A higher percentage of patients who were obese , compared with those of normal weight , were prescribed at least one drug in the following disease categories : cardiovascular ( 36 % versus 20 % ) , central nervous system ( 46 % versus 35 % ) , endocrine ( 26 % versus 18 % ) , and musculoskeletal and joint disease ( 30 % versus 22 % ) . All of these categories had a P-value of < 0.001 . Other categories , such as gastrointestinal ( 24 % versus 18 % ) , infections ( 42 % versus 35 % ) , skin ( 24 % versus 19 % ) had a P-value of < 0.01 , while respiratory diseases ( 18 % versus 21 % ) had a P-value of < 0.05 . Total prescribing volume was significantly higher for the group with obesity and was increased in the region of two- to fourfold in a wide range of prescribing categories : ulcer healing drugs , lipid regulators , beta-adrenoreceptor drugs , drugs affecting the rennin angiotensin system , calcium channel blockers , antibacterial drugs , sulphonylureas , biguanides , non-steroidal anti-inflammatories ( NSAIDs ) ( P<0.001 ) and fibrates , angiotensin II antagonists , and thyroid drugs ( P<0.05 ) . The main impact on prescribing volumes is from numbers of patients treated , although in some areas there is an effect from greater dosage or longer treatment in those who are obese including calcium channel blockers , antihistamines , hypnotics , drugs used in the treatment of nausea and vertigo , biguanides , and NSAIDs ( P<0.05 ) reflected in significantly increased defined daily dose prescribing . CONCLUSIONS This large study of contemporary practice indicates that obesity more than doubled prescribing in most drug categories Background Obesity affects 25 % of the UK adult population but modest weight loss can reduce the incidence of obesity-related chronic disease . Some effective weight loss treatments exist but there is no nationally available National Health Service ( NHS ) treatment service , and general practitioners ( GPs ) rarely discuss weight management with patients or support behavior change . Evidence shows that commercial weight management services , that most primary care trusts have ' on prescription ' , are more effective than primary care treatment . Methods / design We propose a controlled trial where patients will be r and omized to receive either the offer of help by referral to a weight management service and follow-up to assess progress , or advice to lose weight on medical grounds . The primary outcome will be weight change at 12-months . Other questions are : what actions do people take to manage their weight in response to the two GP intervention types ? How do obese patients feel about GPs opportunistically discussing weight management and how does this Output:	We found little convincing evidence for a clinical ly-important effect on participants ' weight or BMI of any of the evaluated interventions . As only two studies reported on cost , we know little about cost effectiveness across the evaluated interventions
MS21275	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: High- quality cancer registry data are essential for assessing trends in incidence rates . This study evaluated the consistency of brain tumor surveillance data using a r and om sample of cases from the Connecticut Tumor Registry . Three neuropathologists independently and blindly review ed tumor slides from 204 cases and a nosologist blindly review ed and assigned International Classification of Diseases for Oncology ( ICD-O ) codes to 326 cases . For the pathology review , absolute concordance was as high as 81 % for all primary brain tumors . Absolute concordance rates were high for nerve sheath ( 89 % ) , meningioma ( 95 % ) , and pituitary ( 95 % ) tumors . Rates were much lower for malignant tumors . ICD-O coding of malignant brain tumors is of relatively high quality with the exception of mixed gliomas and unspecified tumors . A high level of consistency for nonmalignant brain tumor diagnoses suggests that rates for these tumors , when actively reported to a surveillance system , can be of high quality A controlled , prospect i ve , r and omized study evaluated the use of 1,3-bis(2-chloroethyl)-1-nitrosourea ( BCNU ) and /or radiotherapy in the treatment of patients who were operated on and had histological confirmation of anaplastic glioma . A total of 303 patients were r and omized into this study , of whom 222 ( 73 % ) were within the Valid Study Group ( VSG ) , having met the protocol criteria of neuropathology , corticosteroid control , and therapeutic approach . Patients were divided into four r and om groups , and received BCNU ( 80 mg/sq m/day on 3 successive days every 6 to 8 weeks ) , and /or radiotherapy ( 5000 to 6000 rads to the whole brain through bilateral opposing ports ) , or best conventional care but no chemotherapy or radiotherapy . Analysis was performed on all patients who received any amount of therapy ( VSG ) and on the Adequately Treated Group ( ATG ) , who had received 5000 or more rads radiotherapy , two or more courses of chemotherapy , and had a minimum survival of 8 or more weeks ( the interval that would have been required to have received either the radiotherapy or chemotherapy ) . Median survival of patients in the VSG was , best conventional care : 14 weeks ( ATG : 17.0 weeks ) ; BCNU : 18.5 weeks ( ATG : 25.0 weeks ) ; radiotherapy : 35 weeks ( ATG : 37.5 weeks ) ; and BCNU plus radiotherapy : 34.5 weeks ( ATG : 40.5 weeks ) . All therapeutic modalities showed some statistical superiority compared to best conventional care . There was no significant difference between the four groups in relation to age distribution , sex , location of tumor , diagnosis , tumor characteristics , signs or symptoms , or the amount of corticosteroid used . An analysis of prognostic factors indicates that the initial performance status ( Karnofsky rating ) , age , the use of only a surgical biopsy , parietal location , the presence of seizures , or the involvement of cranial nerves II , III , IV , and VI are all of significance . Toxicity included acceptable , reversible thrombocytopenia and leukopenia Abstract Objective : Recently a r and omized placebo-controlled phase III trial of biodegradable polymers containing carmustine has demonstrated a significant survival benefit for patients treated with local chemotherapy . A local chemotherapy applied directly to the resection cavity may act directly on residual tumor cells in adjacent brain possibly leading to a local control of the tumor and increased survival . Methods : We have analyzed the pattern of recurrence using serial MRI studies of 24 patients treated with GLIADEL ® Wafers or placebo wafers following resection of glioblastomas . Results : Of 24 patients 11 received carmustine wafers and 13 placebo . The age distribution and Karnowsky performance scores of the two population s were not different . However , the median survival ( 14.7 versus 9.5 months ; P = 0.007 ) and the time to neurological deterioration ( 12.9 ± 4.85 vs. 9.4 ± 2.73 months ; P = 0.035 ) was significantly longer in the treatment group versus the placebo treated control . Preoperative and follow up MRI studies were evaluated in a blinded fashion . Out of 24 patients that entered the analysis 11 showed clearance of all contrast enhancement following resection of glioblastomas . Seventeen tumors progressed locally and 7 showed different patterns of distant failure . Within the carmustine treated group 8 patients showed a local treatment failure with recurrent tumors immediately adjacent to the resection cavity or progression form a residual tumor . Three patients showed a multifocal distant and local pattern of failure after complete or subtotal removal . In no case the local chemotherapy result ed in a distant recurrence only . However , the time to radiographic progression was 165.1 ± 80.75 days for the GLIADEL ® Wafer group and 101.9 ± 43.06 days for the placebo group ( P = 0.023 ) . Conclusion : In this subgroup analysis of a phase III trial population both the clinical progression and radiological progression were significantly delayed in patients treated with local chemotherapy , result ing in an increased survival time . Local chemotherapy with carmustine containing wafer implants did not result in an altered pattern of recurrence and did not promote multifocal patterns of recurrence A previous placebo-controlled trial has shown that biodegradable 1,3-bis (2-chloroethyl)-1-nitrosourea ( BCNU ) wafers ( Gliadel wafers ) prolong survival in patients with recurrent glioblastoma multiforme . A previously completed phase 3 trial , also placebo controlled , in 32 patients with newly diagnosed malignant glioma also demonstrated a survival benefit in those patients treated with BCNU wafers . Because of the small number of patients in that trial , a larger phase 3 trial was performed to confirm these results . Two hundred forty patients were r and omized to receive either BCNU or placebo wafers at the time of primary surgical resection ; both groups were treated with external beam radiation postoperatively . The two groups were similar for age , sex , Karnofsky performance status ( KPS ) , and tumor histology . Median survival in the intent-to-treat group was 13.9 months for the BCNU wafer-treated group and 11.6 months for the placebo-treated group ( log-rank P -value stratified by country = 0.03 ) , with a 29 % reduction in the risk of death in the treatment group . When adjusted for factors affecting survival , the treatment effect remained positive with a risk reduction of 28 % ( P = 0.03 ) . Time to decline in KPS and in 10/11 neuroperformance measures was statistically significantly prolonged in the BCNU wafer-treated group ( P < /= 0.05 ) . Adverse events were comparable for the 2 groups , except for CSF leak ( 5 % in the BCNU wafer-treated group vs. 0.8 % in the placebo-treated group ) and intracranial hypertension ( 9.1 % in the BCNU wafer-treated group vs. 1.7 % in the placebo group ) . This study confirms that local chemotherapy with BCNU wafers is well tolerated and offers a survival benefit to patients with newly diagnosed malignant glioma The results of a multi-institutional phase I trial evaluating the safety of surgically implanted biodegradable 1,3-bis(chloro-ethyl)-1-nitrosourea ( BCNU ) impregnated polymer as theinitial therapy for malignant brain tumors are reported . This is the first study of locally delivered BCNU and st and ard external beam radiation therapy ( XRT ) given concurrently . Twenty-two patients were treated at three hospitals . The entry criteria were : single unilateral tumor focus larger than 1 cm3 ; age over 18 years ; Karnofsky Performance Score ( KPS ) of at least 60 h ; and an intra-operative diagnosis of malignant glioma . Twenty-one of twenty-two patients had glioblastoma multiforme . After surgery , seven or eight BCNU-loaded polyanhydride polymer discs ( 7.7 mg BCNU each ) were placed in the resection cavity . Postoperatively , all patients received st and ard radiation therapy ; none received additional chemotherapy in the first 6 months . Neurotoxicity , systemic toxicity , and survival were assessed . No perioperative mortality was seen . Neurotoxicity was equivalent to that occurring in other series of patients undergoing craniotomy and XRT without local chemotherapy . Systematic ally , no significant bone marrow suppression occurred , and there were no wound infections . Median survival in this group of older patients ( mean age=60 ) was 42 weeks , 8 patients survived 1 year , and 4 patients survived more than 18 months . Interstitial chemotherapy with BCNU-polymer with subsequent radiation therapy appears to be safe as an initial therapy . Several long-term survivors in this group of older patients with predominantly glioblastoma suggests efficacy in some patients . Dose escalation and efficacy trials are planned to further evaluate interstitial chemotherapy for the initial treatment of malignant gliomas This clinical study was design ed to evaluate the safety and efficacy of the sustained release form of dibutryl adenosine-3′,5′-cyclic monophosphate ( dB-cAMP , bucladesine ) placed in the tumor resection cavity at the time of recurrence of the de novo glioblastoma multiforme ( GBM ) patients .In a r and omized prospect i ve manner , 40 patients who were diagnosed as GBM in their first operations were included in this study . Four different therapy protocol s were used : First group of 10 patients had tumor resection only . Second group assessed had only systemic chemotherapy as six i.v . infusions of fotémustine after tumor resection . Third group had implantation of bucladesine-loaded biodegradable polymeric sustained release ( bcl-SR ) pellets while the last group received six i.v . infusions of systemic fotémustine as in the second group in addition to local implantation of bcl-SR pellets . A biodegradable polymer , poly-dl-lactide-co-glycolide with molecular weight of 80 000 , was used as carrier matrix for the drug with an approximately 4–5 months of release time . Maximal doses of 20 mg of bucladesine with a mean dose of 15.5 mg were implanted . No bone marrow suppression occurred and there were no wound infections as far as the local bucladesine-loaded polymer therapy is concerned . In this r and omized prospect i ve trial of local interstitial chemotherapy with long acting bcl-SR did show a statistically significant delay of recurrence on the treatment of GBM patients . Best treatment results obtained from the local bcl-SR + systemic fotémustine treated group in which survival rate estimated by the Kaplan – Meier method was 70 % in de novo GBM at 12 months OBJECTIVE To find out the effect of carmustine ( bischloroethyl-nitrosourea ) combined with a biodegradable polymer in the treatment of malignant ( Grade s III and IV ) gliomas , applied locally , at the time of the primary operation . METHODS Prospect i ve , r and omized double-blind study of an active treatment group versus a placebo group . Conducted at the Departments of Neurosurgery of the University Hospitals of Helsinki , Tampere , and Turku in Finl and and Trondheim in Norway . The study consisted of 32 patients ( 16 in each treatment group ) enrolled between March 23 , 1992 , and March 19 , 1993 . The study was planned to include 100 patients but had to be terminated prematurely , because the drug that was being used had become unobtainable . The main outcome measures included the survival times of patients after the operations and the application of an active drug or placebo . RESULTS The median time from surgery to death was 58.1 weeks for the active treatment group versus 39.9 weeks for the placebo group ( P = 0.012 ) . For 27 patients with Grade IV tumors , the corresponding times were 39.9 weeks for the placebo group and 53.3 weeks for the active treatment group ( P = 0.008 ) . At the end of the study , six patients were still alive , five of whom belonged to the active treatment group . CONCLUSION Carmustine applied locally in a biodegradable polymer at the time of primary operation , seems to have a favorable effect on the life span of patients with high- grade gliomas Abstract Glioblastoma multiforme ( GBM ) makes up as many as 30 % of all primary brain tumors . Despite the employment of multimodal antitumor treatment , the overall survival is less than one year . Between 06/01/1998 and 06/01/2000 17 patients ( Group A ) with GBM ( 11 males , 6 females ; median age 54.3 years ) were administered local chemotherapy with cisplatin incorporated into biodegradable 6-carboxylcellulose polymer ( cisplatin-depot ( CDDP-D ) ) . After the subtotal removal of GBM , twenty 1.5 × 1.5 cm polymer plates with a total area of 45 cm2 ( the density of cisplatin immobilization on 6-carboxylcellulose being 1 mg/cm2 , a total cisplatin dose of 45 mg ) were implanted into the tumor bed . Group B ( 21 patients with GBM ; 11 males , 10 females ; median age 53.2 years ) was control : the subtotal tumor ablation without CD Output:	Gliadel(R ) results in a prolongation of survival without an increased incidence of adverse events when used as primary therapy . There is no evidence of enhanced progression free survival ( PFS ) or QOL . In recurrent disease , Gliadel(R ) does not appear to confer any added benefit .
MS21276	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Rituximab is an effective treatment in patients with established rheumatoid arthritis ( RA ) . The objective of the IMAGE study was to determine the efficacy of rituximab in the prevention of joint damage and its safety in combination with methotrexate ( MTX ) in patients initiating treatment with MTX . Methods In this double-blind r and omised controlled phase III study , 755 MTX-naïve patients with active RA were r and omly assigned to MTX alone , rituximab 2 × 500 mg + MTX or rituximab 2 × 1000 mg + MTX . The primary end point at week 52 was the change in joint damage measured using a Genant-modified Sharp score . Results 249 , 249 and 250 patients were r and omly assigned to MTX alone , rituximab 2 × 500 mg + MTX or rituximab 2 × 1000 mg + MTX , respectively . At week 52 , treatment with rituximab 2 × 1000 mg + MTX compared with MTX alone was associated with a reduction in progression of joint damage ( mean change in total modified Sharp score 0.359 vs 1.079 ; p=0.0004 ) and an improvement in clinical outcomes ( ACR50 65 % vs 42 % ; p<0.0001 ) ; rituximab 2 × 500 mg + MTX improved clinical outcomes ( ACR50 59 % vs 42 % ; p<0.0001 ) compared with MTX alone but did not significantly reduce the progression of joint damage . Safety outcomes were similar between treatment groups . Conclusions Treatment with rituximab 2 × 1000 mg in combination with MTX is an effective therapy for the treatment of patients with MTX-naïve RA . CLinical Trials.gov identifier NCT00299104 Objectives This phase III study evaluated the efficacy and safety of rituximab plus methotrexate ( MTX ) in patients with active rheumatoid arthritis ( RA ) who had an inadequate response to MTX and who were naïve to prior biological treatment . Methods Patients with active disease on stable MTX ( 10–25 mg/week ) were r and omised to rituximab 2 × 500 mg ( n=168 ) , rituximab 2 × 1000 mg ( n=172 ) , or placebo ( n=172 ) . From week 24 , patients not in remission ( Disease Activity Score ( 28 joints ) ≥2.6 ) received a second course of rituximab ; patients initially assigned to placebo switched to rituximab 2 × 500 mg . The primary end point was American College of Rheumatology 20 ( ACR20 ) response at week 24 . All patients were followed until week 48 . Results At week 24 , both doses of rituximab showed statistically superior efficacy ( p<0.0001 ) to placebo ( ACR20 : 54 % , 51 % and 23 % ; rituximab ( 2 × 500 mg ) + MTX , rituximab ( 2 × 1000 mg ) + MTX and placebo + MTX , respectively ) . Secondary end points were also significantly improved for both rituximab groups compared with placebo . Further improvements in both rituximab arms were observed from week 24 to week 48 . Rituximab + MTX was well tolerated , demonstrating comparable safety to placebo + MTX through to week 24 , and between rituximab doses through to week 48 . Conclusions Rituximab ( at 2 × 500 mg and 2 × 1000 mg ) plus MTX significantly improved clinical outcomes at week 24 , which were further improved by week 48 . No significant differences in either clinical or safety outcomes were apparent between the rituximab doses BACKGROUND An open-label study indicated that selective depletion of B cells with the use of rituximab led to sustained clinical improvements for patients with rheumatoid arthritis . To confirm these observations , we conducted a r and omized , double-blind , controlled study . METHODS We r and omly assigned 161 patients who had active rheumatoid arthritis despite treatment with methotrexate to receive one of four treatments : oral methotrexate ( > or = 10 mg per week ) ( control ) ; rituximab ( 1000 mg on days 1 and 15 ) ; rituximab plus cyclophosphamide ( 750 mg on days 3 and 17 ) ; or rituximab plus methotrexate . Responses defined according to the criteria of the American College of Rheumatology ( ACR ) and the European League against Rheumatism ( EULAR ) were assessed at week 24 ( primary analyses ) and week 48 ( exploratory analyses ) . RESULTS At week 24 , the proportion of patients with 50 percent improvement in disease symptoms according to the ACR criteria , the primary end point , was significantly greater with the rituximab-methotrexate combination ( 43 percent , P=0.005 ) and the rituximab-cyclophosphamide combination ( 41 percent , P=0.005 ) than with methotrexate alone ( 13 percent ) . In all groups treated with rituximab , a significantly higher proportion of patients had a 20 percent improvement in disease symptoms according to the ACR criteria ( 65 to 76 percent vs. 38 percent , P < or = 0.025 ) or had EULAR responses ( 83 to 85 percent vs. 50 percent , P < or = 0.004 ) . All ACR responses were maintained at week 48 in the rituximab-methotrexate group . The majority of adverse events occurred with the first rituximab infusion : at 24 weeks , serious infections occurred in one patient ( 2.5 percent ) in the control group and in four patients ( 3.3 percent ) in the rituximab groups . Peripheral-blood immunoglobulin concentrations remained within normal ranges . CONCLUSIONS In patients with active rheumatoid arthritis despite methotrexate treatment , a single course of two infusions of rituximab , alone or in combination with either cyclophosphamide or continued methotrexate , provided significant improvement in disease symptoms at both weeks 24 and 48 R and omized controlled trials often suffer from two major complications , i.e. , noncompliance and missing outcomes . One potential solution to this problem is a statistical concept called intention-to-treat ( ITT ) analysis . ITT analysis includes every subject who is r and omized according to r and omized treatment assignment . It ignores noncompliance , protocol deviations , withdrawal , and anything that happens after r and omization . ITT analysis maintains prognostic balance generated from the original r and om treatment allocation . In ITT analysis , estimate of treatment effect is generally conservative . A better application of the ITT approach is possible if complete outcome data are available for all r and omized subjects . Per- protocol population is defined as a subset of the ITT population who completed the study without any major protocol violations Background In the IMAGE study , rituximab plus methotrexate ( MTX ) inhibited joint damage and improved clinical outcomes at 1 year in MTX-naïve patients with early active rheumatoid arthritis . Objective The aim of this study was to assess joint damage progression and clinical outcomes over 2 years . Methods Patients ( n=755 ) were r and omised to receive rituximab 2 × 500 mg+MTX , 2 × 1000 mg+MTX or placebo+MTX . The placebo-controlled period continued to week 104 . Two-year end points were defined as secondary or exploratory and included change in total Genant-modified Sharp score ( mTSS ) , total erosion score and joint space narrowing score from baseline to week 104 . Clinical efficacy and physical function end points were also assessed . Results At 2 years , rituximab 2 × 1000 mg+MTX maintained inhibition of progressive joint damage versus MTX alone ( mTSS change 0.41 vs 1.95 ; p<0.0001 ( 79 % inhibition ) ) , and a higher proportion of patients receiving rituximab 2 × 1000 mg+MTX had no radiographic progression over 2 years compared with those receiving MTX alone ( 57 % vs 37 % ; p<0.0001 ) . Contrary to 1-year results , exploratory analysis of rituximab 2 × 500 mg+MTX at 2 years showed that progressive joint damage was slowed by ∼61 % versus placebo+MTX ( mTSS , exploratory p=0.0041 ) . Improvements in clinical signs and symptoms and physical function seen after 1 year in rituximab-treated patients versus those receiving placebo were maintained at year 2 . Safety profiles were similar between groups . Conclusions Treatment with rituximab 2 × 1000 mg+MTX was associated with sustained improvements in radiographic , clinical and functional outcomes over 2 years . Clinical trials.gov identifier NCT00299104 Objective . To evaluate the efficacy and safety of three dosing and repeat treatment regimens of rituximab ( RTX ) plus MTX in patients with active RA . Methods . Patients with active RA despite stable MTX ( 10–25 mg/week ) were r and omly assigned to one of the three treatment regimens comprising two courses of RTX given 24 weeks apart : 2 × 500 and 2 × 500 mg ; 2 × 500 and 2 × 1000 mg ( dose escalation ) ; and 2 × 1000 and 2 × 1000 mg . The primary endpoint was proportion of patients achieving ACR20 at Week 48 . Results . At Week 48 , ACR20 responses were not statistically significantly different between the dose regimens . Compared with RTX 2 × 500 mg ( n = 134 ) or dose escalation ( n = 119 ) , ACR and European League Against Rheumatism ( EULAR ) outcomes in the RTX 2 × 1000 mg group ( n = 93 ) were consistently higher , with significantly more patients achieving EULAR responses ( P = 0.0495 ) . At Week 48 , rituximab 2 × 1000 mg was associated with a higher proportion of patients who , following retreatment , maintained or improved their Week 24 responses . Dose escalation from 2 × 500 to 2 × 1000 mg did not appear to be associated with improved outcomes compared with continual 2 × 500 mg . All RTX regimens demonstrated comparable safety . Conclusions . RTX 2 × 500 and 2 × 1000 mg could not be clearly differentiated , although some efficacy outcomes suggest improved outcomes in the rituximab 2 × 1000 mg group . Retreatment from Week 24 result ed in a sustained suppression of disease activity through to Week 48 . Trial registration . Clinical Trials.gov , http:// clinical trials.gov/ , NCT00422383 OBJECTIVE To define clinical ly meaningful changes in 2 widely used health-related quality of life ( HQL ) instruments in studies of patients with rheumatoid arthritis ( RA ) . METHODS Patients with RA ( n = 693 ) who were enrolled in 2 double-blind , placebo-controlled clinical trials completed the Short Form 36 ( SF-36 ) modified health survey and the Health Assessment Question naire ( HAQ ) disability index at baseline and 6-week followup assessment s. Data on 5 RA severity measures were also collected at baseline and at 6 weeks ( patient and physician global assessment s , joint swelling and tenderness counts , and global pain assessment ) . Comparison of changes in the SF-36 scales and HAQ scores was made between groups of patients known to differ in the level of change on each RA severity measure . RESULTS With few exceptions , changes in the SF-36 and HAQ scores were different between patients who differed in the level of change on each RA severity measure . Changes in the SF-36 and HAQ scores were more strongly related to changes in the patient and physician global assessment s and patient pain assessment than to changes in the joint swelling and tenderness counts . CONCLUSION Based on these results , minimally important changes in the SF-36 scales and HAQ disability scores were determined , which will be useful in interpreting HQL results in clinical trials OBJECTIVE To examine the efficacy and safety of different rituximab doses plus methotrexate ( MTX ) , with or without glucocorticoids , in patients with active rheumatoid arthritis ( RA ) resistant to disease-modifying antirheumatic drugs ( DMARDs ) , including biologic agents . METHODS A total of 465 patients were r and omized into 9 treatment groups : 3 rituximab groups ( placebo [ n = 149 ] , 500 mg [ n = 124 ] , or 1,000 mg [ n = 192 ] on days 1 and 15 ) each also taking either placebo glucocorticoids , intravenous methylprednisolone premedication , or intravenous methylprednisolone premedication plus oral prednisone for 2 weeks . All patients received MTX ( 10 - 25 mg Output:	CONCLUSION Low-dose RTX has similar effectiveness and met noninferiority criteria for most primary outcomes .
MS21277	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Symptoms in polycystic liver disease ( PLD ) are thought to be caused by compression of organs and structures by the enlarged liver . Aim The aim of this article is to assess the impact of liver volume on symptoms and quality of life ( QoL ) in PLD . Methods We included PLD patients from two prospect i ve studies that used the PLD- question naire ( PLD-Q ) for symptom assessment . QoL was assessed through SF-36 , summarized in a physical ( PCS ) and mental ( MCS ) component score . Liver volume was correlated with PLD-Q total scores . Patients were classified based on height-corrected liver volume in mild ( < 1600 ml ) , moderate ( 1600–3200 ml ) , and severe ( > 3200 ml ) disease . PLD-Q and QoL ( PCS and MCS ) scores were compared across disease stages . Results We included 82 of 131 patients from the original studies ( disease stages ; mild n = 26 , moderate n = 33 , and severe n = 23 ) . Patients with larger liver volume reported higher symptom burden ( r = 0.516 , p < 0.001 ) . Symptom scores increased with disease progression , except for abdominal pain ( p = 0.088 ) . PCS decreased with advancing disease ( p < 0.001 ) , in contrast to MCS ( p = 0.055 ) . Moderate ( p = 0.007 ) and severe ( p < 0.001 ) PLD patients had lower PCS scores than the general population . Conclusion PLD with larger liver volume is more likely to be symptomatic and is associated with lower BACKGROUND & AIMS Therapy for polycystic liver is invasive , expensive , and has disappointing long-term results . Treatment with somatostatin analogues slowed kidney growth in patients with polycystic kidney disease ( PKD ) and reduced liver and kidney volume in a PKD rodent model . We evaluated the effects of lanreotide , a somatostatin analogue , in patients with polycystic liver because of autosomal-dominant ( AD ) PKD or autosomal-dominant polycystic liver disease ( PCLD ) . METHODS We performed a r and omized , double-blind , placebo-controlled trial in 2 tertiary referral centers . Patients with polycystic liver ( n = 54 ) were r and omly assigned to groups given lanreotide ( 120 mg ) or placebo , administered every 28 days for 24 weeks . The primary end point was the difference in total liver volume , measured by computerized tomography at weeks 0 and 24 . Analyses were performed on an intention-to-treat basis . RESULTS Baseline characteristics were comparable for both groups , except that more patients with ADPKD were assigned to the placebo group ( P = .03 ) . The mean liver volume decreased 2.9 % , from 4606 mL ( 95 % confidence interval ( CI ) : 547 - 8665 ) to 4471 mL ( 95 % CI : 542 - 8401 mL ) , in patients given lanreotide . In the placebo group , the mean liver volume increased 1.6 % , from 4689 mL ( 95 % CI : 613 - 8765 mL ) to 4895 mL ( 95 % CI : 739 - 9053 mL ) ( P < .01 ) . Post hoc stratification for patients with ADPKD or PCLD revealed similar changes in liver volume , with statistically significant differences in patients given lanreotide ( P < .01 for both diseases ) . CONCLUSIONS In patients with polycystic liver , 6 months of treatment with lanreotide reduces liver volume There are no proven , effective therapies for polycystic kidney disease ( PKD ) or polycystic liver disease ( PLD ) . We enrolled 42 patients with severe PLD result ing from autosomal dominant PKD ( ADPKD ) or autosomal dominant PLD ( ADPLD ) in a r and omized , double-blind , placebo-controlled trial of octreotide , a long-acting somatostatin analogue . We r and omly assigned 42 patients in a 2:1 ratio to octreotide LAR depot ( up to 40 mg every 28+/-5 days ) or placebo for 1 year . The primary end point was percent change in liver volume from baseline to 1 year , measured by MRI . Secondary end points were changes in total kidney volume , GFR , quality of life , safety , vital signs , and clinical laboratory tests . Thirty-four patients had ADPKD , and eight had ADPLD . Liver volume decreased by 4.95%+/-6.77 % in the octreotide group but remained practically unchanged ( + 0.92%+/-8.33 % ) in the placebo group ( P=0.048 ) . Among patients with ADPKD , total kidney volume remained practically unchanged ( + 0.25%+/-7.53 % ) in the octreotide group but increased by 8.61%+/-10.07 % in the placebo group ( P=0.045 ) . Changes in GFR were similar in both groups . Octreotide was well tolerated ; treated individuals reported an improved perception of bodily pain and physical activity . In summary , octreotide slowed the progressive increase in liver volume and total kidney volume , improved health perception among patients with PLD , and had an acceptable side effect profile BACKGROUND The course of autosomal dominant polycystic kidney disease ( ADPKD ) is often associated with pain , hypertension , and kidney failure . Pre clinical studies indicated that vasopressin V(2)-receptor antagonists inhibit cyst growth and slow the decline of kidney function . METHODS In this phase 3 , multicenter , double-blind , placebo-controlled , 3-year trial , we r and omly assigned 1445 patients , 18 to 50 years of age , who had ADPKD with a total kidney volume of 750 ml or more and an estimated creatinine clearance of 60 ml per minute or more , in a 2:1 ratio to receive tolvaptan , a V(2)-receptor antagonist , at the highest of three twice-daily dose regimens that the patient found tolerable , or placebo . The primary outcome was the annual rate of change in the total kidney volume . Sequential secondary end points included a composite of time to clinical progression ( defined as worsening kidney function , kidney pain , hypertension , and albuminuria ) and rate of kidney-function decline . RESULTS Over a 3-year period , the increase in total kidney volume in the tolvaptan group was 2.8 % per year ( 95 % confidence interval [ CI ] , 2.5 to 3.1 ) , versus 5.5 % per year in the placebo group ( 95 % CI , 5.1 to 6.0 ; P<0.001 ) . The composite end point favored tolvaptan over placebo ( 44 vs. 50 events per 100 follow-up-years , P=0.01 ) , with lower rates of worsening kidney function ( 2 vs. 5 events per 100 person-years of follow-up , P<0.001 ) and kidney pain ( 5 vs. 7 events per 100 person-years of follow-up , P=0.007 ) . Tolvaptan was associated with a slower decline in kidney function ( reciprocal of the serum creatinine level , -2.61 [ mg per milliliter](-1 ) per year vs. -3.81 [ mg per milliliter](-1 ) per year ; P<0.001 ) . There were fewer ADPKD-related adverse events in the tolvaptan group but more events related to aquaresis ( excretion of electrolyte-free water ) and hepatic adverse events unrelated to ADPKD , contributing to a higher discontinuation rate ( 23 % , vs. 14 % in the placebo group ) . CONCLUSIONS Tolvaptan , as compared with placebo , slowed the increase in total kidney volume and the decline in kidney function over a 3-year period in patients with ADPKD but was associated with a higher discontinuation rate , owing to adverse events . ( Funded by Otsuka Pharmaceuticals and Otsuka Pharmaceutical Development and Commercialization ; TEMPO 3:4 Clinical Trials.gov number , NCT00428948 . ) BACKGROUND AND OBJECTIVES No medical treatment is available for polycystic liver disease , a frequent manifestation of autosomal-dominant polycystic kidney disease ( ADPKD ) . In a prospect i ve , r and omized , double-blind , crossover study , 6 months of octreotide ( 40 mg every 28 days ) therapy limited kidney volume growth more effectively than placebo in 12 patients with ADPKD . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS In this secondary , post hoc analysis of the above study , octreotide-induced changes in liver volumes compared with placebo and the relationship between concomitant changes in liver and kidney volumes were evaluated . Those analyzing liver and kidney volumes were blinded to treatment . RESULTS Liver volumes significantly decreased from 1595 + /- 478 ml to 1524 + /- 453 ml with octreotide whereas they did not appreciably change with placebo . Changes in liver volumes were significantly different between the two treatment periods ( -71 + /- 57 ml versus + 14 + /- 85 ml ) . Octreotide-induced liver volume reduction was fully explained by a reduction in parenchyma volume from 1506 + /- 431 ml to 1432 + /- 403 ml . Changes in liver volumes were significantly correlated with concomitant changes in kidney volumes ( r = 0.67 ) during octreotide but not during placebo treatment . Liver and kidney volume changes significantly differed with both treatments ( octreotide : -71 + /- 57 ml versus + 71 + /- 107 ; placebo : + 14 + /- 85 ml versus + 162 + /- 114 ) , but net reductions in liver ( -85 + /- 103 ml ) and kidney ( -91 + /- 125 ml ) volume growth on octreotide versus placebo were similar . CONCLUSIONS Octreotide therapy reduces liver volumes in patients with ADPKD and is safe Background In a previous trial involving patients with early autosomal dominant polycystic kidney disease ( ADPKD ; estimated creatinine clearance , ≥60 ml per minute ) , the vasopressin V2‐receptor antagonist tolvaptan slowed the growth in total kidney volume and the decline in the estimated glomerular filtration rate ( GFR ) but also caused more elevations in aminotransferase and bilirubin levels . The efficacy and safety of tolvaptan in patients with later‐stage ADPKD are unknown . Methods We conducted a phase 3 , r and omized withdrawal , multicenter , placebo‐controlled , double‐blind trial . After an 8‐week prer and omization period that included sequential placebo and tolvaptan run‐in phases , during which each patient 's ability to take tolvaptan without dose‐limiting side effects was assessed , 1370 patients with ADPKD who were either 18 to 55 years of age with an estimated GFR of 25 to 65 ml per minute per 1.73 m2 of body‐surface area or 56 to 65 years of age with an estimated GFR of 25 to 44 ml per minute per 1.73 m2 were r and omly assigned in a 1:1 ratio to receive tolvaptan or placebo for 12 months . The primary end point was the change in the estimated GFR from baseline to follow‐up , with adjustment for the exact duration that each patient participated ( interpolated to 1 year ) . Safety assessment s were conducted monthly . Results The change from baseline in the estimated GFR was ‐2.34 ml per minute per 1.73 m2 ( 95 % confidence interval [ CI ] , ‐2.81 to ‐1.87 ) in the tolvaptan group , as compared with ‐3.61 ml per minute per 1.73 m2 ( 95 % CI , ‐4.08 to ‐3.14 ) in the placebo group ( difference , 1.27 ml per minute per 1.73 m2 ; 95 % CI , 0.86 to 1.68 ; P<0.001 ) . Elevations in the alanine aminotransferase level ( to > 3 times the upper limit of the normal range ) occurred in 38 of 681 patients ( 5.6 % ) in the tolvaptan group and in 8 of 685 ( 1.2 % ) in the placebo group . Elevations in the aminotransferase level were reversible after stopping tolvaptan . No elevations in the bilirubin level of more than twice the upper limit of the normal range were detected . Conclusions Tolvaptan result ed in a slower decline than placebo in the estimated GFR over a 1‐year period in patients with later‐stage ADPKD . ( Funded by Otsuka Pharmaceuticals and Otsuka Pharmaceutical Development and Commercialization ; REPRISE Clinical Trials.gov number , NCT02160145 . BACKGROUND & Output:	There was no effect on progression to ESRF . Somatostatin analogues were associated with known adverse effects such as gastrointestinal symptoms . Conclusions The available RCT data show improvement in TLV with somatostatin analogue treatment . There was no benefit to TKV or eGFR in patients with ADPKD , while being associated with various side effects .
MS21278	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Hypersensitivity to a variety of sensory stimuli is a feature of persistent whiplash associated disorders ( WAD ) . However , little is known about sensory disturbances from the time of injury until transition to either recovery or symptom persistence . Quantitative sensory testing ( pressure and thermal pain thresholds , the brachial plexus provocation test ) , the sympathetic vasoconstrictor reflex and psychological distress ( GHQ‐28 ) were prospect ively measured in 76 whiplash subjects within 1 month of injury and then 2 , 3 and 6 months post‐injury . Subjects were classified at 6 months post‐injury using scores on the Neck Disability Index : recovered ( < 8 ) , mild pain and disability ( 10–28 ) or moderate/severe pain and disability ( > 30 ) . Sensory and sympathetic nervous system tests were also measured in 20 control subjects . All whiplash groups demonstrated local mechanical hyperalgesia in the cervical spine at 1 month post‐injury . This hyperalgesia persisted in those with moderate/severe symptoms at 6 months but resolved by 2 months in those who had recovered or reported persistent mild symptoms . Only those with persistent moderate/severe symptoms at 6 months demonstrated generalised hypersensitivity to all sensory tests . These changes occurred within 1 month of injury and remained unchanged throughout the study period . Whilst no significant group differences were evident for the sympathetic vasoconstrictor response , the moderate/severe group showed a tendency for diminished sympathetic reactivity . GHQ‐28 scores of the moderate/severe group were higher than those of the other two groups . The differences in GHQ‐28 did not impact on any of the sensory measures . These findings suggest that those with persistent moderate/severe symptoms at 6 months display , soon after injury , generalised hypersensitivity suggestive of changes in central pain processing mechanisms . This phenomenon did not occur in those who recover or those with persistent mild symptoms & NA ; Dysfunction in the motor system is a feature of persistent whiplash associated disorders . Little is known about motor dysfunction in the early stages following injury and of its progress in those persons who recover and those who develop persistent symptoms . This study measured prospect ively , motor system function ( cervical range of movement ( ROM ) , joint position error ( JPE ) and activity of the superficial neck flexors ( EMG ) during a test of cranio‐cervical flexion ) as well as a measure of fear of re‐injury ( TAMPA ) in 66 whiplash subjects within 1 month of injury and then 2 and 3 months post injury . Subjects were classified at 3 months post injury using scores on the neck disability index : recovered ( < 8 ) , mild pain and disability ( 10–28 ) or moderate/severe pain and disability ( > 30 ) . Motor system function was also measured in 20 control subjects . All whiplash groups demonstrated decreased ROM and increased EMG ( compared to controls ) at 1 month post injury . This deficit persisted in the group with moderate/severe symptoms but returned to within normal limits in those who had recovered or reported persistent mild pain at 3 months . Increased EMG persisted for 3 months in all whiplash groups . Only the moderate/severe group showed greater JPE , within 1 month of injury , which remained unchanged at 3 months . TAMPA scores of the moderate/severe group were higher than those of the other two groups . The differences in TAMPA did not impact on ROM , EMG or JPE . This study identifies , for the first time , deficits in the motor system , as early as 1 month post whiplash injury , that persisted not only in those reporting moderate/severe symptoms at 3 months but also in subjects who recovered and those with persistent mild symptoms There has been little investigation into whether or not differences exist in the nature of physical impairment associated with neck pain of whiplash and insidious origin . This study examined the neck flexor synergy during performance of the cranio-cervical flexion test , a test targeting the action of the deep neck flexors . Seventy-five volunteer subjects participated in this study and were equally divided between Group 1 , asymptomatic control subjects , Group 2 , subjects with insidious onset neck pain and Group 3 , subjects with neck pain following a whiplash injury . The cranio-cervical flexion test was performed in five progressive stages of increasing cranio-cervical flexion range . Subjects ' performance was guided by feedback from a pressure sensor inserted behind the neck which monitored the slight flattening of the cervical lordosis which occurs with the contraction of longus colli . Myoelectric signals ( EMG ) were detected from the muscles during performance of the test . The results indicated that both the insidious onset neck pain and whiplash groups had higher measures of EMG signal amplitude ( normalized root mean square ) in the sternocleidomastoid during each stage of the test compared to the control subjects ( all P<0.05 ) and had significantly greater shortfalls from the pressure targets in the test stages ( P<0.05 ) . No significant differences were evident between the neck pain groups in either parameter indicating that this physical impairment in the neck flexor synergy is common to neck pain of both whiplash and insidious origin Background : Exposure to a whiplash injury implies a risk for development of chronic disability and h and icap , with reported frequencies ranging from 0 % to 50 % in follow-up studies . The exact risk for development of chronic whiplash syndrome is not known . Objective : To prospect ively determine the sensitivity and specificity of five possible predictors for h and icap following a whiplash injury . Methods : In a 1-year prospect i ve study of persons with acute whiplash injury ( n = 141 ) and control subjects who had acute ankle distortion ( n = 40 ) , pain intensity , number of nonpainful neurologic complaints , cervical mobility , workload during extension and flexion of the neck , and results of psychometric assessment were recorded . The consecutively sample d injured persons were assessed with structured and semistructured question naires , and underwent neurologic examination after 1 week and 1 , 3 , 6 , and 12 months . After 3 to 4 years , participants with whiplash injury were question ed about legal issues . Results : After 1 year , 11 ( 7.8 % ) persons with whiplash injury had not returned to usual level of activity or work . The best single estimator of h and icap was the cervical range-of-motion test , which had a sensitivity of 73 % and a specificity of 91 % ( p < 0.01 , Cox regression analysis ) . Accuracy and specificity increased to 94 % and 99 % when combined with pain intensity and other complaints . This increase was gained at the expense of a reduced sensitivity . Initiation of lawsuit within first month after injury did not influence recovery . Conclusion : The cervical range-of-motion test has a high sensitivity in prediction of h and icap after acute whiplash injury . The value of cervical range-of-motion test is further improved by additional recording of symptoms and pain intensity & NA ; Predictors of outcome following whiplash injury are limited to socio‐demographic and symptomatic factors , which are not readily amenable to secondary and tertiary intervention . This prospect i ve study investigated the predictive capacity of early measures of physical and psychological impairment on pain and disability 6 months following whiplash injury . Motor function ( ROM ; kinaesthetic sense ; activity of the superficial neck flexors ( EMG ) during cranio‐cervical flexion ) , quantitative sensory testing ( pressure , thermal pain thresholds , brachial plexus provocation test ) , sympathetic vasoconstrictor responses and psychological distress ( GHQ‐28 , TSK , IES ) were measured in 76 acute whiplash participants . The outcome measure was Neck Disability Index scores at 6 months . Stepwise regression analysis was used to predict the final NDI score . Logistic regression analyses predicted membership to one of the three groups based on final NDI scores ( < 8 recovered , 10–28 mild pain and disability , > 30 moderate/severe pain and disability ) . Higher initial NDI score ( 1.007–1.12 ) , older age ( 1.03–1.23 ) , cold hyperalgesia ( 1.05–1.58 ) , and acute post‐traumatic stress ( 1.03–1.2 ) predicted membership to the moderate/severe group . Additional variables associated with higher NDI scores at 6 months on stepwise regression analysis were : ROM loss and diminished sympathetic reactivity . Higher initial NDI score ( 1.03–1.28 ) , greater psychological distress ( GHQ‐28 ) ( 1.04–1.28 ) and decreased ROM ( 1.03–1.25 ) predicted subjects with persistent milder symptoms from those who fully recovered . These results demonstrate that both physical and psychological factors play a role in recovery or non‐recovery from whiplash injury . This may assist in the development of more relevant treatment methods for acute whiplash Abstract Higher initial levels of pain and disability , older age , cold hyperalgesia , impaired sympathetic vasoconstriction and moderate post‐traumatic stress symptoms have been shown to be associated with poor outcome 6 months following whiplash injury . This study prospect ively investigated the predictive capacity of these variables at a long‐term follow‐up . Sixty‐five of an initial cohort of 76 acutely injured whiplash participants were followed to 2–3 years post‐accident . Motor function ( ROM ; kinaesthetic sense ; activity of the superficial neck flexors ( EMG ) during cranio‐cervical flexion ) , quantitative sensory testing ( pressure , thermal pain thresholds and brachial plexus provocation test ) , sympathetic vasoconstrictor responses and psychological distress ( GHQ‐28 , TSK and IES ) were measured . The outcome measure was Neck Disability Index ( NDI ) scores . Participants with ongoing moderate/severe symptoms at 2–3 years continued to manifest decreased ROM , increased EMG during cranio‐cervical flexion , sensory hypersensitivity and elevated levels of psychological distress when compared to recovered participants and those with milder symptoms . The latter two groups showed only persistent deficits in cervical muscle recruitment patterns . Higher initial NDI scores ( OR 1.00–1.1 ) , older age ( OR 1.00–1.13 ) , cold hyperalgesia ( OR 1.1–1.13 ) and post‐traumatic stress symptoms ( OR 1.03–1.2 ) remained significant predictors of poor outcome at long‐term follow‐up ( r2 = 0.56 ) . The robustness of these physical and psychological factors suggests that their assessment in the acute stage following whiplash injury will be important BACKGROUND AND PURPOSE Physical mechanisms are the possible factors involved in the development and maintenance of long-term h and icaps after acute whiplash injury . This study prospect ively examined the role of active neck mobility , cervical and extra-cervical pains , as well as non-painful complaints after a whiplash injury as predictors for subsequent h and icap . METHODS Consecutive acute whiplash patients ( n = 688 ) were interviewed and examined by a study nurse after the median of 5 days after injury , and divided into a high- or a low-risk group by an algorithm based on pain intensity , number of non-painful complaints and active neck mobility [ active cervical range of motion ( CROM ) ] . All 458 high-risk patients and 230 low-risk patients received mailed question naires after 3 , 6 and 12 months . Two examiners examined all high-risk patients ( n = 458 ) and 41 consecutive low-risk patients at median 11 , 109 , 380 days after injury . The main outcome measures were : h and icaps , severe headaches , neck pain and neck disability . RESULTS The relative risk for a 1-year disability increased by 3.5 with initial intense neck pain and headaches , by 4.6 times with reduced CROM and by four times with multiple non-painful complaints . CONCLUSION Reduced active neck mobility , immediate intense neck pain and headaches and the presence of multiple non-painful complaints are the important prognostic factors for a 1-year h and icap after acute whiplash Study Design . An experimental study of motor and sensory function and psychological distress in subjects with acute whiplash injury . Objectives . To characterize acute whiplash injury in terms of motor and sensory systems dysfunction and psychological distress and to compare subjects with higher and lesser levels of pain and disability . Summary of Background Data . Motor system dysfunction , sensory hypersensitivity , and psychological distress are present in chronic whiplash associated disorders ( WAD ) , but little is known of such factors in the acute stage of injury . As higher levels of pain and disability in acute WAD are accepted as signs of poor outcome , further characterization of this group from those with lesser symptoms is important . Material s and Methods . Motor function ( cervical range of movement [ ROM ] , joint position error [ JPE ] ; activity of the superficial neck flexors [ EMG ] during a test of cranio-cervical flexion ) , quantitative sensory testing ( pressure , thermal pain thresholds , and responses to the brachial plexus provocation test ) , and psychological distress ( GHQ-28 , TAMPA , IES ) were measured in 80 whiplash subjects ( WAD II or III ) within 1 month of injury , as were 20 control subjects . Results . Three subgroups were identified in the cohort using cluster analysis based on the Neck Disability Index : those with mild , moderate , or severe pain and disability . All whiplash groups demonstrated decreased ROM and increased EMG compared with the controls ( all P < 0.01 ) . Only the Output:	The predictive value of examining the presence of cervical motor dysfunctions was doubtful . The course and predictive value of initial reduced cervical mobility was inconsistent . Cervical motor dysfunctions are present soon after whiplash trauma persisting in those with moderate/severe symptoms . However , these dysfunctions have limited predictive value , and hence may not explain the complex clinical picture of whiplash-associated disorders .
MS21279	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To compare the efficacy of combination therapy , with erythromycin and metoclopramide , to erythromycin alone in the treatment of feed intolerance in critically ill patients . DESIGN R and omized , controlled , double-blind trial . SETTING Mixed medical and surgical intensive care unit . PATIENTS Seventy-five mechanically ventilated , medical patients with feed intolerance ( gastric residual volume ≥250 mL ) . INTERVENTIONS Patients received either combination therapy ( n = 37 ; 200 mg of intravenous erythromycin twice daily + 10 mg of intravenous metoclopramide four times daily ) or erythromycin alone ( n = 38 ; 200 mg of intravenous erythromycin twice daily ) in a prospect i ve , r and omized fashion . Gastric feeding was re-commenced and 6-hourly gastric aspirates performed . Patients were studied for 7 days . Successful feeding was defined as a gastric residual volume < 250 mL with the feeding rate ≥40 mL/hr , over 7 days . Secondary outcomes included daily caloric intake , vomiting , postpyloric feeding , length of stay , and mortality . MEASUREMENTS AND MAIN RESULTS Demographic data ; use of inotropes , opioids , or benzodiazepines ; and pretreatment gastric residual volume were similar between the two groups . The gastric residual volume was significantly lower after 24 hrs of treatment with combination therapy , compared with erythromycin alone ( 136 ± 23 mL vs. 293 ± 45 mL , p = .04 ) . Over the 7 days , patients treated with combination therapy had greater feeding success , received more daily calories , and had a lower requirement for postpyloric feeding , compared with erythromycin alone . Tachyphylaxis occurred in both groups but was less with combination therapy . Sedation , higher pretreatment gastric residual volume , and hypoalbuminemia were significantly associated with a poor response . There was no difference in the length of hospital stay or mortality rate between the groups . Watery diarrhea was more common with combination therapy ( 20 of 37 vs. 10 of 38 , p = .01 ) but was not associated with enteric infections , including Clostridium difficile . CONCLUSIONS In critically ill patients with feed intolerance , combination therapy with erythromycin and metoclopramide is more effective than erythromycin alone in improving the delivery of nasogastric nutrition and should be considered as the first-line treatment . ( Crit Care Med . 2007;35:2561 - 2567 . ) NQ Nguyen , M Chapman , RJ Fraser , LK Bryant , C Burgstad , RH Holloway Introduction : Our aim was to evaluate the impact of hyperproteic hypocaloric enteral feeding on clinical outcomes in critically ill patients , particularly on severity of organic failure measured with the Sequential Organ Failure Assessment ( SOFA ) . Material s and Methods : In a double blind clinical trial , 80 critically ill adult patients were r and omized to hyperproteic hypocaloric or to isocaloric enteral nutrition ; all patients completed follow-up of at least 4 days . Prescribed caloric intake was : Hyperproteic hypocaloric enteral nutrition ( 15 kcal/kg with 1.7 g/kg of protein ) or isocaloric enteral nutrition ( 25 kcal/kg with 20 % of the calories as protein ) . The main outcome was the differences in delta SOFA at 48 h. Secondary outcomes were intensive care unit ( ICU ) length of stay , days on ventilator , hyperglycemic events , and insulin requirements . Results : There were no differences in SOFA score at baseline ( 7.5 ( st and ard deviation ( SD ) 2.9 ) vs 6.7 ( SD 2.5 ) P = 0.17 ) . The total amount of calories delivered was similarly low in both groups ( 12 kcal/kg in intervention group vs 14 kcal/kg in controls ) , but proteic delivery was significantly different ( 1.4 vs 0.76 g/kg , respectively P ≤ 0.0001 ) . The intervention group showed an improvement in SOFA score at 48 h ( delta SOFA 1.7 ( SD 1.9 ) vs 0.7 ( SD 2.8 ) P = 0.04 ) and less hyperglycemic episodes per day ( 1.0 ( SD 1.3 ) vs 1.7 ( SD 2.5 ) P = 0.017 ) . Discussion : Enteral hyperproteic hypocaloric nutrition therapy could be associated with a decrease in multiple organ failure measured with SOFA score . We also found decreased hyperglycemia and a trend towards less mechanical ventilation days and ICU length of stay This document represents the first collaboration between 2 organizations — the American Society for Parenteral and Enteral Nutrition and the Society of Critical Care Medicine — to describe best practice s in nutrition therapy in critically ill children . The target of these guidelines is intended to be the pediatric critically ill patient ( > 1 month and 2–3 days in a PICU admitting medical , surgical , and cardiac patients . In total , 2032 citations were scanned for relevance . The PubMed / MEDLINE search result ed in 960 citations for clinical trials and 925 citations for cohort studies . The EMBASE search for clinical trials culled 1661 citations . In total , the search for clinical trials yielded 1107 citations , whereas the cohort search yielded 925 . After careful review , 16 r and omized controlled trials and 37 cohort studies appeared to answer 1 of the 8 preidentified question groups for this guideline . We used the GRADE criteria ( Grading of Recommendations , Assessment , BACKGROUND Despite extensive use of enteral ( EN ) and parenteral nutrition ( PN ) in intensive care unit ( ICU ) population s for 4 decades , evidence to support their efficacy is extremely limited . METHODS A prospect i ve r and omized trial was conducted evaluate the impact on outcomes of intensive medical nutrition therapy ( IMNT ; provision of > 75 % of estimated energy and protein needs per day via EN and adequate oral diet ) from diagnosis of acute lung injury ( ALI ) to hospital discharge compared with st and ard nutrition support care ( SNSC ; st and ard EN and ad lib feeding ) . The primary outcome was infections ; secondary outcomes included number of days on mechanical ventilation , in the ICU , and in the hospital and mortality . RESULTS Overall , 78 patients ( 40 IMNT and 38 SNSC ) were recruited . No significant differences between groups for age , body mass index , disease severity , white blood cell count , glucose , C-reactive protein , energy or protein needs occurred . The IMNT group received significantly higher percentage of estimated energy ( 84.7 % vs 55.4 % , P < .0001 ) and protein needs ( 76.1 vs 54.4 % , P < .0001 ) per day compared with SNSC . No differences occurred in length of mechanical ventilation , hospital or ICU stay , or infections . The trial was stopped early because of significantly greater hospital mortality in IMNT vs SNSC ( 40 % vs 16 % , P = .02 ) . Cox proportional hazards models indicated the hazard of death in the IMNT group was 5.67 times higher ( P = .001 ) than in the SNSC group . CONCLUSIONS Provision of IMNT from ALI diagnosis to hospital discharge increases mortality BACKGROUND Nutritional support has been recognized as an essential part of intensive care unit management . However , the appropriate caloric intake for critically ill patients remains ill defined . OBJECTIVE We examined the effect of permissive underfeeding compared with that of target feeding and of intensive insulin therapy ( IIT ) compared with that of conventional insulin therapy ( CIT ) on the outcomes of critically ill patients . DESIGN This study had a 2 × 2 factorial , r and omized , controlled design . Eligible patients were r and omly assigned to permissive underfeeding or target feeding groups ( caloric goal : 60 - 70 % compared with 90 - 100 % of calculated requirement , respectively ) with either IIT or CIT ( target blood glucose : 4.4 - 6.1 compared with 10 - 11.1 mmol/L , respectively ) . RESULTS Twenty-eight-day all-cause mortality was 18.3 % in the permissive underfeeding group compared with 23.3 % in the target feeding group ( relative risk : 0.79 ; 95 % CI : 0.48 , 1.29 ; P = 0.34 ) . Hospital mortality was lower in the permissive underfeeding group than in the target group ( 30.0 % compared with 42.5 % ; relative risk : 0.71 ; 95 % CI : 0.50 , 0.99 ; P = 0.04 ) . No significant differences in outcomes were observed between the IIT and CIT groups . CONCLUSION In critically ill patients , permissive underfeeding may be associated with lower mortality rates than target feeding . This trial was registered at controlled-trials.com as IS RCT N96294863 IMPORTANCE Monitoring of residual gastric volume is recommended to prevent ventilator-associated pneumonia ( VAP ) in patients receiving early enteral nutrition . However , studies have challenged the reliability and effectiveness of this measure . OBJECTIVE To test the hypothesis that the risk of VAP is not increased when residual gastric volume is not monitored compared with routine residual gastric volume monitoring in patients receiving invasive mechanical ventilation and early enteral nutrition . DESIGN , SETTING , AND PATIENTS R and omized , noninferiority , open-label , multicenter trial conducted from May 2010 through March 2011 in adults requiring invasive mechanical ventilation for more than 2 days and given enteral nutrition within 36 hours after intubation at 9 French intensive care units ( ICUs ) ; 452 patients were r and omized and 449 included in the intention-to-treat analysis ( 3 withdrew initial consent ) . INTERVENTION Absence of residual gastric volume monitoring . Intolerance to enteral nutrition was based only on regurgitation and vomiting in the intervention group and based on residual gastric volume greater than 250 mL at any of the 6 hourly measurements and regurgitation or vomiting in the control group . MAIN OUTCOME MEASURES Proportion of patients with at least 1 VAP episode within 90 days after r and omization , as assessed by an adjudication committee blinded to patient group . The prestated noninferiority margin was 10 % . RESULTS In the intention-to-treat population , VAP occurred in 38 of 227 patients ( 16.7 % ) in the intervention group and in 35 of 222 patients ( 15.8 % ) in the control group ( difference , 0.9 % ; 90 % CI , -4.8 % to 6.7 % ) . There were no significant between-group differences in other ICU-acquired infections , mechanical ventilation duration , ICU stay length , or mortality rates . The proportion of patients receiving 100 % of their calorie goal was higher in the intervention group ( odds ratio , 1.77 ; 90 % CI , 1.25 - 2.51 ; P = .008 ) . Similar results were obtained in the per- protocol population . CONCLUSION AND RELEVANCE Among adults requiring mechanical ventilation and receiving early enteral nutrition , the absence of gastric volume monitoring was not inferior to routine residual gastric volume monitoring in terms of development of VAP . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01137487 Introduction To compare outcomes from early post-pyloric to gastric feeding in ventilated , critically ill patients in a medical intensive care unit ( ICU ) . Methods Prospect i ve r and omized study . Ventilated patients were r and omly assigned to receive enteral feed via a nasogastric or a post-pyloric tube . Post-pyloric tubes were inserted by the bedside nurse and placement was confirmed radiographically . Results A total of 104 patients were enrolled , 54 in the gastric group and 50 in the post-pyloric group . Bedside post-pyloric tube insertion was successful in 80 % of patients . Patients who failed post-pyloric insertion were fed via the nasogastric route , but were analysed on an intent-to treat basis . A per protocol analysis was also performed . Baseline characteristics were similar for all except Acute Physiology and Chronic Health Evaluation II ( APACHE II ) score , which was higher in the post-pyloric group . There was no difference in length of stay or ventilator days . The gastric group was quicker to initiate feed 4.3 hours ( 2.9 - 6.5 hours ) as compared to post-pyloric group 6.6 hours ( 4.5 - 13.0 hours ) ( P = 0.0002 ) . The time to reach target feeds from admission was also faster in gastric group : 8.7 hours ( 7.6 - 13.0 hours ) compared to 12.3 hours ( 8.9 - 17.5 hours ) . The average daily energy and protein deficit were lower in gastric group 73 Kcal ( 2 - 288 Kcal ) and 3.5 g ( 0 - 15 g ) compared to 167 Kcal ( 70 - 41 Output:	The associations between lower compared with higher caloric intake and primary and secondary outcomes , including pneumonia , were not different between caloric restriction and non-caloric restriction trials , except for the hospital stay which was longer with lower caloric intake in the caloric restriction trials . Conclusions We found no association between the dose of caloric intake in adult critically ill patients and hospital mortality . Lower caloric intake was associated with lower risk of blood stream infections and incident renal replacement therapy ( five trials only ) .
MS21280	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Carcinoma of the larynx is the most common cancer affecting the head and neck region . In Northern Europe , early laryngeal cancer is almost universally treated by irradiation , but elsewhere it is treated by surgery . The main aim of this study was to determine whether there was any difference in survival between the two main therapeutic options . The secondary aim was to assess speech and voice quality in a small , r and omized sample of patients from each treatment group Cancer of the larynx is the most prevalent non-cutaneous malignancy of the head neck region and its treatment presents a threat to both natural speech and survival . This study examines the manner in which two separate specialties in the same and different geographic regions vary in their opinions about the treatment of glottic laryngeal cancer . The goal was to define options available to patients and to classify controversies about optimal treatment which might be resolved in clinical trials . Question naires depicting different presentations of glottic larynx cancer were mailed to 1649 otolaryngologists and radiation oncologists in North America , Europe and Australasia . Half the doctors were asked to describe their preferred treatment for a patient while the others were asked to imagine that they themselves were the patient . In all the disease situations opinions varied significantly with respect to the treatment modality advised ( whether to employ surgical or radiotherapy approaches ) and in more extensive disease situations the intention of treatment also varied depending on whether a curative approach should involve conservation or loss of the larynx . Doctors also recommended similar treatment for their patients as they would for themselves . Apart from disease extent the most significant variables influencing recommendations were the physicians ' specialty ( P = 0.0001 ) and where they practice ( P = 0.0001 ) . These findings demonstrate diversity of opinion which is influenced more profoundly by the traditions of the specialties and geographic location of practice than by the reported results of treatments for laryngeal cancer . Convictions about optimal management have become barriers to the assessment of the relative value of different treatments and to ensuring that patients are fully informed about management options . The profession should regard as a high priority efforts to resolve these therapeutic conflicts which are associated with major differences in quality of life Both radiotherapy and laser surgery give excellent results in the treatment of T1a glottic carcinoma . In this study , we compared the outcome of these treatment options . Demographic details and continuous follow-up with exact cause of death have been recorded prospect ively for 351 patients with T1a glottic carcinoma at a tertiary referral centre in two consecutive decennia 1986–2005 . Patients were treated with radiotherapy ( 163 patients ) until 1996 when laser surgery was adopted as primary treatment ( 188 patients ) . The minimum follow-up time was 29 months . Neither the estimated 5-year disease-free survival , the disease-specific survival nor the crude survival differ between the two treatment options . The incidence of mainly local recurrences was equal during the first 3 years , followed by an increase in number of recurrences in the laser-operated patients . The odds ratio for a laryngectomy was 13.5 in patients treated with radiotherapy ( P = 0.002 ) , but mortality due to recurrence did not differ between the groups . The incidence of second primaries was equal ( 11 % ) but death due to second primaries differed significantly , favouring laser-treated patients ( P = 0.003 ) . In conclusion , the relative risk for a laryngectomy when a tumour recurs is 12.7 times higher in patients primarily treated with irradiation for T1a laryngeal carcinoma , compared with patients treated with laser surgery . Regarding the treatment costs , treatment impact on patients and organ preservation , we consider laser therapy to be the better treatment option for patients with T1a glottic cancer as no difference in survival could be observed OBJECTIVE To compare the functional and oncologic outcomes of transoral CO₂ laser microsurgery relative to radiotherapy for early-stage glottic carcinoma . DESIGN Functional analysis : population -based , prospect i ve , nonr and omized consecutive series of stage 1 and 2 glottic carcinoma treated with laser surgery ( n = 54 ) or radiotherapy ( n = 25 ) . Oncologic analysis : population -based , historical cohort comparing laser surgery ( n = 54 ) and radiotherapy ( n = 76 ) . SETTING Academic cancer centre . METHODS AND OUTCOME MEASURES Functional results were prospect ively collected prior to treatment and at 3 , 6 , 12 , and 24 months following treatment using vali date d performance scales assessing general level of function , speech , and swallowing . Oncologic results were collected from a larger cohort from the cancer registry of CancerCare MB . RESULTS Laser surgery result ed in a voice that was less likely to be understood all the time ( Performance Status Scale for Head and Neck Cancer Patients : underst and ability score < 100 ; OR = 12.2 ; p = .03 ) and a higher likelihood of having a Voice H and icap Index ( VHI-10 ) score of 10 or more ( OR = 16.2 ; p = .001 ) . Five-year laryngectomy-free survival rates for laser versus radiation were 87 versus 76 % ( p = .16 ) . Subset analysis revealed that stage 1 5-year laryngeal preservation rates for laser ( n = 51 ) versus radiation ( n = 46 ) were 100 versus 86 % ( p = .02 ) . CONCLUSIONS There is a higher likelihood of hoarseness after laser surgery , but the severity of this h and icap is mild in most patients . Laser microsurgery results in excellent laryngeal preservation rates , which may exceed those of radiation In 1980 - 1987 , a cooperative r and omized study of 363 patients with stage III laryngeal cancer ( T1 - 3N0 - 1M0 ) was carried out . In 249 patients tumor was located in the vestibular space and in 114 in the vocal cord area ; 78.5 % of the patients had no regional metastases ( N0 ) and 21.5 % had metastases ( N1 ) . Combined therapy was applied to 251 patients , 135 of which were first exposed to radiotherapy and then to surgery and 116 were first exposed to surgery and then radiotherapy . In 71 patients , regional zones underwent preventive treatment ( in 24 patients elective radiotherapy and in 47 preventive removal of the cervical fat were used ) . In 112 patients , the therapeutic protocol was modified due to different reasons ( 69 patients underwent only surgery and 43 radical radiotherapy ) . The therapeutic results were assessed in terms of three parameters : incidence of relapses and regional metastases , relapse-free time , and survival . This approach revealed no significant differences in the efficacy of the different protocol s of the combined treatment . The 5-year survival rate of the patients with vestibular and cord space tumor was 77.9 % and 80.7 % respectively , when treated according to the radiotherapy + surgery protocol , and 82.8 % and 89.2 % , respectively , when treated according to the surgery + radiotherapy protocol . Comparison of preventive approaches showed that the 5-year survival rate increased by 92 % as a result of removal of the subcutaneous fat from the neck area Background : Transoral laser assisted microsurgical resection of early glottic laryngeal cancer is a relatively new treatment modality that is practised in many centres across the UK . In the absence of the results from r and omised clinical trials , clinicians may be guided by an expert panel consensus statement on transoral laser assisted microsurgical resection of early squamous cell cancer of the larynx Output:	RESULTS There is no evidence in favor of 1 treatment modality when considering likelihood of local control or overall survival . There is a suggestion that RT may be associated with less measureable perturbation of voice as compared to surgery , but no significant differences were seen in patient perception . The likelihood of laryngeal preservation may be higher when surgery can be offered as initial treatment . For patients with early ( T1 ) glottic cancer , treatment options include the equally effective endolaryngeal surgery , with or without laser , or radiation therapy .
MS21281	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE . The study tested whether a combined environmental and educational intervention solely promoting water consumption was effective in preventing overweight among children in elementary school . METHODS . The participants in this r and omized , controlled cluster trial were second- and third- grade rs from 32 elementary schools in socially deprived areas of 2 German cities . Water fountains were installed and teachers presented 4 prepared classroom lessons in the intervention group schools ( N = 17 ) to promote water consumption . Control group schools ( N = 15 ) did not receive any intervention . The prevalence of overweight ( defined according to the International Obesity Task Force criteria ) , BMI SD scores , and beverage consumption ( in glasses per day ; 1 glass was defined as 200 mL ) self-reported in 24-hour recall question naires , were determined before ( baseline ) and after the intervention . In addition , the water flow of the fountains was measured during the intervention period of 1 school year ( August 2006 to June 2007 ) . RESULTS . Data on 2950 children ( intervention group : N = 1641 ; control group : N = 1309 ; age , mean ± SD : 8.3 ± 0.7 years ) were analyzed . After the intervention , the risk of overweight was reduced by 31 % in the intervention group , compared with the control group , with adjustment for baseline prevalence of overweight and clustering according to school . Changes in BMI SD scores did not differ between the intervention group and the control group . Water consumption after the intervention was 1.1 glasses per day greater in the intervention group . No intervention effect on juice and soft drink consumption was found . Daily water flow of the fountains indicated lasting use during the entire intervention period , but to varying extent . CONCLUSION . Our environmental and educational , school-based intervention proved to be effective in the prevention of overweight among children in elementary school , even in a population from socially deprived areas OBJECTIVE A multidimensional lifestyle intervention performed in 652 preschoolers ( 72 % of migrant , 38 % of low educational level ( EL ) parents ) reduced body fat , but not BMI and improved fitness . The objective of this study is to examine whether the intervention was equally effective in children of migrant and /or low EL parents . METHODS Cluster-r and omized controlled single blinded trial , conducted in 2008/09 in 40 r and omly selected preschools in Switzerl and . The culturally tailored intervention consisted of a physical activity program and lessons on nutrition , media use and sleep . Primary outcomes included BMI and aerobic fitness . Secondary outcomes included % body fat , waist circumference and motor agility . RESULTS Children of migrant parents benefitted similarly from the intervention compared to their counterparts ( p for interaction≥ 0.09 ) . However , children of low EL parents benefitted less , although these differences did not reach statistical significance ( p for interaction≥ 0.06 ) . Average intervention effect sizes for BMI were -0.10 , -0.05 , -0.11 and 0.04 kg/m(2 ) and for aerobic fitness were 0.55 , 0.20 , 0.37 and -0.05 stages for children of non-migrant , migrant , middle/high EL and low EL parents , respectively . CONCLUSIONS This intervention was similarly effective among preschoolers of migrant parents compared to their counterparts , while children of low EL parents benefitted less PURPOSE A positive outcome in self-reported behavior could be detected erroneously if an intervention caused over-reporting of the targeted behavior . Data collected from a multi-site r and omized trial were examined to determine if adolescent girls who received a physical activity intervention over-reported their activity more than girls who received no intervention . METHODS Activity was measured using accelerometers and self-reports ( 3-Day Physical Activity Recall , 3DPAR ) in cross-sectional sample s preintervention ( 6th grade , n = 1,464 ) and post-intervention ( 8th grade , n = 3,114 ) . Log-transformed accelerometer minutes were regressed on 3DPAR blocks , treatment group , and their interaction , while adjusting for race , body mass index , and timing of data collection . RESULTS Preintervention , the association between measures did not differ between groups , but post-intervention 3DPAR blocks were associated with fewer log-accelerometer minutes of moderate-vigorous physical activity ( MVPA ) in intervention girls than in control girls ( p = 0.002 ) . The group difference was primarily in the upper 15 % of the 3DPAR distribution , where control girls had > 1.7 more accelerometer minutes of MVPA than intervention girls who reported identical activity levels . Group differences in this sub sample were 8.5%-16.2 % of the mean activity levels ; the intervention was powered to detect a difference of 10 % . CONCLUSION Self-report measures should be interpreted with caution when used to evaluate a physical activity intervention Objective To test the effect of a multidimensional lifestyle intervention on aerobic fitness and adiposity in predominantly migrant preschool children . Design Cluster r and omised controlled single blinded trial ( Ballabeina study ) over one school year ; r and omisation was performed after stratification for linguistic region . Setting 40 preschool classes in areas with a high migrant population in the German and French speaking regions of Switzerl and . Participants 652 of the 727 preschool children had informed consent and were present for baseline measures ( mean age 5.1 years ( SD 0.7 ) , 72 % migrants of multicultural origins ) . No children withdrew , but 26 moved away . Intervention The multidimensional culturally tailored lifestyle intervention included a physical activity programme , lessons on nutrition , media use ( use of television and computers ) , and sleep and adaptation of the built environment of the preschool class . It lasted from August 2008 to June 2009 . Main outcome measures Primary outcomes were aerobic fitness ( 20 m shuttle run test ) and body mass index ( BMI ) . Secondary outcomes included motor agility , balance , percentage body fat , waist circumference , physical activity , eating habits , media use , sleep , psychological health , and cognitive abilities . Results Compared with controls , children in the intervention group had an increase in aerobic fitness at the end of the intervention ( adjusted mean difference : 0.32 stages ( 95 % confidence interval 0.07 to 0.57 ; P=0.01 ) but no difference in BMI ( −0.07 kg/m2 , −0.19 to 0.06 ; P=0.31 ) . Relative to controls , children in the intervention group had beneficial effects in motor agility ( −0.54 s , −0.90 to −0.17 ; P=0.004 ) , percentage body fat ( −1.1 % , −2.0 to −0.2 ; P=0.02 ) , and waist circumference ( −1.0 cm , −1.6 to −0.4 ; P=0.001 ) . There were also significant benefits in the intervention group in reported physical activity , media use , and eating habits , but not in the remaining secondary outcomes . Conclusions A multidimensional intervention increased aerobic fitness and reduced body fat but not BMI in predominantly migrant preschool children . Trial registration Clinical Trials NCT00674544 Background The prevalence of infant obesity is increasing , but there is a lack of evidence -based approaches to prevent obesity at this age . This study tested the acceptability and feasibility of evaluating a theory-based intervention aim ed at reducing risk of obesity in infants of overweight/obese women during and after pregnancy : the Healthy and Active Parenting Programme for Early Years ( HAPPY ) . Methods A feasibility r and omised controlled trial was conducted in Bradford , Engl and . One hundred twenty overweight/obese pregnant women ( Body Mass Index [ BMI ] ≥25 kg/m2 ) were recruited between 10–26 weeks gestation . Consenting women were r and omly allocated to HAPPY ( 6 antenatal , 6 postnatal sessions : N = 59 ) or usual care ( N = 61 ) . Appropriate outcome measures for a full trial were explored , including : infant ’s length and weight , woman ’s BMI , physical activity and dietary intake of the women and infants . Health economic data were collected . Measurement occurred before r and omisation and when the infant was aged 6 months and 12 months . Feasibility outcomes were : recruitment/attrition rates , and acceptability of : r and omisation , measurement , and intervention . Intra-class correlations for infant weight were calculated . Fidelity was assessed through observations and facilitator feedback . Focus groups and semi-structured interviews explored acceptability of methods , implementation , and intervention content . Results Recruitment targets were met ( ~20 women/month ) with a recruitment rate of 30 % of eligible women ( 120/396 ) . There was 30 % attrition at 12 months ; 66 % of recruited women failed to attend intervention sessions , but those who attended the first session were likely to continue to attend ( mean 9.4/12 sessions , range 1–12 ) . Reaction to intervention content was positive , and fidelity was high . Group clustering was minimal ; an adjusted effect size of −0.25 st and ard deviation scores for infant weight at 12 months ( 95 % CI : −0.16–0.65 ) favouring the intervention was observed using intention to treat analyses . No adverse events were reported . Conclusions The HAPPY intervention appeared feasible and acceptable to participants who attended and those delivering it , however attendance was low ; adaptations to increase initial attendance are recommended . Whilst the study was not powered to detect a definitive effect , our results suggest a potential to reduce risk of infant obesity . The evidence reported provides valuable lessons to inform progression to a definitive trial . Trial Registration Current Controlled Trials IS RCT Objective To assess feasibility and acceptability of a multifaceted , culturally appropriate intervention for preventing obesity in South Asian children , and to obtain data to inform sample size for a definitive trial . Design Phase II feasibility study of a complex intervention . Setting 8 primary schools in inner city Birmingham , UK , within population s that are predominantly South Asian . Participants 1090 children aged 6–8 years took part in the intervention . 571 ( 85.9 % from South Asian background ) underwent baseline measures . 85.5 % ( n=488 ) were followed up 2 years later . Interventions The 1-year intervention consisted of school-based and family-based activities , targeting dietary and physical activity behaviours . The intervention was modified and refined throughout the period of delivery . Main outcome measures Acceptability and feasibility of the intervention and of measurements required to assess outcomes in a definitive trial . The difference in body mass index ( BMI ) z-score between arms was used to inform sample size calculations for a definitive trial . Results Some intervention components ( increasing school physical activity opportunities , family cooking skills workshops , signposting of local leisure facilities and attending day event at a football club ) were feasible and acceptable . Other components were acceptable , but not feasible . Promoting walking groups was neither acceptable nor feasible . At follow-up , children in the intervention compared with the control group were less likely to be obese ( OR 0.41 ; 0.19 to 0.89 ) , and had lower adjusted BMI z-score ( −0.15 kg/m2 ; 95 % CI −0.27 to −0.03 ) . Conclusions The feasibility study informed components for an intervention programme . The favourable direction of outcome for weight status in the intervention group supports the need for a definitive trial . A cluster r and omised controlled trial is now underway to assess the clinical and cost-effectiveness of the intervention . Trial registration number IS RCT N51016370 OBJECTIVE To determine risk factors for consumption of soda and other sugar-sweetened beverages ( SSB ) among 2-year-old children . DESIGN The analysis was performed using three linked data sets : the 2004 - 2005 Oregon Pregnancy Risk Assessment Monitoring Survey ( PRAMS ) ; its longitudinal follow-up , 2006 - 2007 Oregon PRAMS-2 ; and 2004 - 2005 Oregon birth certificates . SETTING PRAMS is a surveillance programme supported by the federal Centers for Disease Control and Prevention and implemented by participating state health departments . Using mixed methods , PRAMS surveys women 2 - 6 months after a live birth . Oregon PRAMS-2 re-interviews respondents shortly after the index child 's second birthday . Oregon PRAMS over sample s minority women . SUBJECTS Using monthly cohorts , we r and omly selected 5851 women from the 2004 - 2005 birth certificates . In total 1911 women completed both PRAMS and PRAMS-2 . The weighted response rate of PRAMS-2 was 43.5 % . RESULTS Almost half of mothers ( 49.9 % ) reported that their child drank SSB on at least 1 d/week . Mothers whose children drank SSB at least once weekly were more likely to have low income ( adjusted OR=2.83 , 95 % CI 2.09 , 3.83 ) and to eat out on ≥2 d/week ( OR=2.11 % , 95 % CI 1.66 , 2.70 ) . Hispanic and non-Hispanic black women were most likely to report that their child drank SSB at least once weekly . CONCLUSIONS Half of mothers reported that their 2-year-old children drank SSB at least once weekly . Public health interventions and policies should address childhood SSB consumption including educating health-care providers and parents OBJECTIVES The purpose of this study Output:	In general , modest positive effects were found but interventions were limited by a short follow-up duration .
MS21282	*TASK* the task is to summarize an input biomedical literature in six sentences *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 /hypothesisUsing the Echantillon Généraliste de Bénéficiaires : r and om 1/97 permanent sample of the French national healthcare insurance system data base ( EGB ) , we investigated whether , as previously suspected , the risk of cancer in insulin glargine ( A21Gly , B31Arg , B32Arg human insulin ) users is higher than in human insulin users . The investigation period was from 1 January 2003 to 30 June 2010 . Methods We used Cox proportional hazards time-dependent models that were stratified on propensity score quartiles for use of insulin glargine vs human insulin , and adjusted for insulin , biguanide and sulfonylurea possession rates to assess the risk of cancer or death in all or incident exclusive or predominant ( ≥80 % use time ) users of insulin glargine compared with equivalent human insulin users . Results Only type 2 diabetic patients were studied . Exposure rates varied from 2,273 and 614 patient-years for incident exclusive users of insulin glargine or human insulin , respectively , to 3125 and 2341 patient-years for all patients predominantly using insulin glargine or human insulin , respectively . All-type cancer HRs with insulin glargine vs human insulin ranged from 0.59 ( 95 % CI 0.28 , 1.25 ) in incident exclusive users to 0.58 ( 95 % CI 0.34 , 1.01 ) in all predominant users . Cancer risk increased with exposure to insulin or sulfonylureas in these patients . Adjusted HRs for death or cancer associated with insulin glargine compared with human insulin ranged from 0.58 ( 95 % CI 0.32 , 1.06 ) to 0.56 ( 95 % CI 0.36 , 0.87 ) . Conclusions /interpretationThere was no excess risk of cancer in type 2 diabetic patients on insulin glargine alone compared with those on human insulin alone . The overall risk of death or cancer in patients on insulin glargine was about half that of patients on human insulin , thereby excluding a competitive risk bias Aims /hypothesisObservational and mechanistic studies have suggested a possible relationship between treatment with metformin and decreased incidence of cancer in participants with type 2 diabetes . We extracted data for malignancies from the ADOPT ( A Diabetes Outcome Progression Trial ) and RECORD ( Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycaemia in Diabetes ) r and omised controlled clinical trials , in which the efficacy and /or safety of metformin was assessed in comparison with sulfonylureas and rosiglitazone . Methods Neoplasm occurrences were collected as adverse events in these studies . We review ed and re-analysed the individual participant data in both studies for serious adverse events , malignancies reported as adverse events and related neoplasms of special interest . Results In ADOPT , 50 participants ( 3.4 % ) on metformin and 55 ( 3.8 % ) on each of rosiglitazone and glibenclamide ( known as glyburide in the USA and Canada ) developed serious adverse event malignancies ( excluding non-melanoma skin cancers ) . This corresponds to 1.03 , 1.12 and 1.31 per 100 person-years , giving hazard ratios for metformin of 0.92 ( 95 % CI 0.63–1.35 ) vs rosiglitazone and 0.78 ( 0.53–1.14 ) vs glibenclamide . In RECORD , on a background of sulfonylurea , 69 ( 6.1 % ) participants developed malignant neoplasms in the metformin group , compared with 56 ( 5.1 % ) in the rosiglitazone group ( HR 1.22 [ 0.86–1.74 ] ) . On a background of metformin , 74 ( 6.7 % ) participants in the sulfonylurea group developed malignant neoplasms , compared with 57 ( 5.1 % ) in the rosiglitazone group ( HR 1.33 [ 0.94–1.88 ] ) . Conclusions /interpretationThe malignancy rates in these two r and omised controlled clinical trials do not support a view that metformin offers any particular protection against malignancy compared with rosiglitazone . However , they do not refute the possibility of a difference compared with sulfonylureas BACKGROUND The provision of sufficient basal insulin to normalize fasting plasma glucose levels may reduce cardiovascular events , but such a possibility has not been formally tested . METHODS We r and omly assigned 12,537 people ( mean age , 63.5 years ) with cardiovascular risk factors plus impaired fasting glucose , impaired glucose tolerance , or type 2 diabetes to receive insulin glargine ( with a target fasting blood glucose level of ≤95 mg per deciliter [ 5.3 mmol per liter ] ) or st and ard care and to receive n-3 fatty acids or placebo with the use of a 2-by-2 factorial design . The results of the comparison between insulin glargine and st and ard care are reported here . The co primary outcomes were nonfatal myocardial infa rct ion , nonfatal stroke , or death from cardiovascular causes and these events plus revascularization or hospitalization for heart failure . Microvascular outcomes , incident diabetes , hypoglycemia , weight , and cancers were also compared between groups . RESULTS The median follow-up was 6.2 years ( interquartile range , 5.8 to 6.7 ) . Rates of incident cardiovascular outcomes were similar in the insulin-glargine and st and ard-care groups : 2.94 and 2.85 per 100 person-years , respectively , for the first co primary outcome ( hazard ratio , 1.02 ; 95 % confidence interval [ CI ] , 0.94 to 1.11 ; P=0.63 ) and 5.52 and 5.28 per 100 person-years , respectively , for the second co primary outcome ( hazard ratio , 1.04 ; 95 % CI , 0.97 to 1.11 ; P=0.27 ) . New diabetes was diagnosed approximately 3 months after therapy was stopped among 30 % versus 35 % of 1456 participants without baseline diabetes ( odds ratio , 0.80 ; 95 % CI , 0.64 to 1.00 ; P=0.05 ) . Rates of severe hypoglycemia were 1.00 versus 0.31 per 100 person-years . Median weight increased by 1.6 kg in the insulin-glargine group and fell by 0.5 kg in the st and ard-care group . There was no significant difference in cancers ( hazard ratio , 1.00 ; 95 % CI , 0.88 to 1.13 ; P=0.97 ) . CONCLUSIONS When used to target normal fasting plasma glucose levels for more than 6 years , insulin glargine had a neutral effect on cardiovascular outcomes and cancers . Although it reduced new-onset diabetes , insulin glargine also increased hypoglycemia and modestly increased weight . ( Funded by Sanofi ; ORIGIN Clinical Trials.gov number , NCT00069784 . ) OBJECTIVE The antidiabetic properties of metformin are mediated through its ability to activate the AMP-activated protein kinase ( AMPK ) . Activation of AMPK can suppress tumor formation and inhibit cell growth in addition to lowering blood glucose levels . We tested the hypothesis that metformin reduces the risk of cancer in people with type 2 diabetes . RESEARCH DESIGN AND METHODS In an observational cohort study using record-linkage data bases and based in Tayside , Scotl and , U.K. , we identified people with type 2 diabetes who were new users of metformin in 1994–2003 . We also identified a set of diabetic comparators , individually matched to the metformin users by year of diabetes diagnosis , who had never used metformin . In a survival analysis we calculated hazard ratios for diagnosis of cancer , adjusted for baseline characteristics of the two groups using Cox regression . RESULTS Cancer was diagnosed among 7.3 % of 4,085 metformin users compared with 11.6 % of 4,085 comparators , with median times to cancer of 3.5 and 2.6 years , respectively ( P < 0.001 ) . The unadjusted hazard ratio ( 95 % CI ) for cancer was 0.46 ( 0.40–0.53 ) . After adjusting for sex , age , BMI , A1C , deprivation , smoking , and other drug use , there was still a significantly reduced risk of cancer associated with metformin : 0.63 ( 0.53–0.75 ) . CONCLUSIONS These results suggest that metformin use may be associated with a reduced risk of cancer . A r and omized trial is needed to assess whether metformin is protective in a population at high risk for cancer BACKGROUND & AIMS Hyperinsulinemia is a putative colorectal cancer ( CRC ) risk factor . Insulin resistance ( IR ) commonly precedes hyperinsulinemia and can be quantitatively measured by using the homeostasis model assessment -insulin resistance ( HOMA-IR ) index . To date , few studies have directly examined serum insulin as an indicator of CRC risk , and none have reported associations on the basis of HOMA-IR . METHODS We performed a case-cohort study within the Alpha-Tocopherol , Beta-Carotene Cancer Prevention ( ATBC ) Study ( n=29,133 ) . Baseline exposure and fasting serum biomarker data were available for 134 incident CRC case and 399 non-case subjects . HOMA-IR was derived as fasting insulin x fasting glucose/22.5 . Hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) were estimated by using age-adjusted and multivariable-adjusted Cox proportional hazards regression models . RESULTS Median ( interquartile range ) values for serum insulin , glucose , and HOMA-IR were 4.1 ( 2.9 - 7.2 ) mIU/L , 101 ( 94 - 108 ) mg/dL , and 0.99 ( 0.69 - 1.98 ) for case subjects and 4.1 ( 2.7 - 6.1 ) mIU/L , 99 ( 93 - 107 ) mg/dL , and 1.02 ( 0.69 - 1.53 ) for non-case subjects , respectively . On the basis of comparison of the highest versus lowest quartiles for each biomarker , insulin ( HR , 1.84 ; 95 % CI , 1.03 - 3.30 ) and HOMA-IR ( HR , 1.85 ; 95 % CI , 1.06 - 3.24 ) were significantly associated with incident CRC , whereas glucose was marginally associated with incident CRC ( HR , 1.70 ; 95 % CI , 0.92 - 3.13 ) in age-adjusted risk models . However , trends across biomarker quartiles were somewhat inconsistent ( P trend=.12 , .04 , and .12 , respectively ) , and multivariable adjustment generally attenuated the observed risk estimates . CONCLUSIONS Data from this prospect i ve study of male smokers provide limited support for hyperinsulinemia , hyperglycemia , and /or insulin resistance as CRC risk factors OBJECTIVE Controversy remains regarding the association between type 2 diabetes mellitus ( DM ) and colorectal cancer ( CRC ) risk . To clarify and extend the existing data , we prospect ively evaluated the association between self-reported type 2 DM ( onset at > 30 years of age ) and incident CRC , overall and by anatomic subsite , among postmenopausal women in the Iowa Women 's Health Study ( n = 35,230 ) . METHODS After 14 years of follow-up , a total of 870 incident CRC cases were identified through annual linkage to the Iowa Cancer Registry . DM was analyzed as reported at baseline and as a time-dependent variable using information obtained during follow-up . CRC risks were estimated using Cox proportional hazards regression models . RESULTS After adjusting for age , body mass index and other potential confounding variables , the relative risk ( RR ) for women with DM versus women without DM was modestly increased at 1.4 [ 95 % confidence interval ( 95 % CI ) , 1.1 - 1.8 ] . By anatomic subsite , the RR for proximal colon cancer was statistically significantly increased ( RR , 1.9 ; 95 % CI , 1.3 - 2.6 ) , whereas the RRs for distal colon ( RR , 1.1 ; 95 % CI , 0.6 - 1.8 ) and rectal cancer ( RR , 0.8 ; 95 % CI , 0.4 - 1.6 ) were not statistically different from unity . Analyses that included DM ascertained at baseline and follow-up yielded similar results . CONCLUSION In this large , prospect i ve study of postmenopausal women , the association Output:	Post-hoc analysis of r and omized controlled trials did not reveal any significant association between ADM and colorectal cancer risk . Meta- analysis of published studies supports a protective association between metformin use and colorectal cancer risk in patients with diabetes mellitus .
MS21283	*TASK* the task is to summarize an input biomedical literature in six sentences *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 lack of circadian rhythmicity of plasma arginine vasopressin ( AVP ) in primary nocturnal enuresis ( PNE ) in some children is known . The original test protocol is time-consuming and needs excellent compliance by children and parents . The goals of the presented study are the introduction of a simple screening test and the evaluation of the response of treatment using intranasal synthetic vasopressin . Fifty-five children ( aged 8.2 + /- 3.1 years ) with PNE and 15 children ( aged 7.9 + /- 2.4 years ) of a control group were investigated . Using a st and ardized protocol , AVP levels were measured by radioimmunoassay ( RIA ) under controlled water intake 3 times per day over a period of 72 h. Fourteen of 55 tested children ( 25.5 % ) with PNE had a significant decrease in nocturnal AVP when compared to the control group . We measured also an increased nocturnal urine volume and a lower urine osmolality in this enuretic group . Eight of 14 patients ( 57.1 % ) with plasma AVP deficiency ( AVPD ) also had bladder instability . Nine of 14 patients ( 64.3 % ) with AVPD with or without concomitant bladder instability were totally dry during desmopressin treatment , but only 2 ( 14.3 % ) remained dry after discontinuation of treatment . Our data suggest that nocturnal urine osmolality measurement may reflect AVPD and predict a positive treatment outcome The effect of 20 micrograms . desaminocysteine-D-arginine vasopressin intranasally on childhood nocturnal enuresis was studied in a r and omized double-blind cross-over series of 54 children . The wetting was significantly less frequent during the 2 , 3-week periods on desaminocysteine-D-arginine vasopressin than during placebo periods , or during periods without any treatment . The effect of desaminocysteine-D-arginine vasopressin was reproducible and the efficacy of desaminocysteine-D-arginine vasopressin depended on the frequency of wetting before treatment . After discontinuation of the short treatment enuresis recurred immediately . No side effects were noted . We conclude that desaminocysteine-D-arginine vasopressin may well be used in the management of childhood enuresis , especially in situations when an immediate effect is desirable Fifty children with primary nocturnal enuresis were r and omised for a study comparing desmopressin ( DDAVP ) and enuresis alarm . Forty six completed the trial , 24 of whom were treated with 20 micrograms intranasal desmopressin nightly and 22 with enuresis alarm for three months . Failures were crossed over and relapses were continued on the same treatment for a further three months . The improvement rate was 70 % in the group given desmopressin and 86 % in the group treated with alarm ; the difference was not significant . During the first week of treatment the group given desmopressin was significantly dryer , and at the end of the study 10 of these patients relapsed compared with one patient in the group given the alarm . No serious side effects were observed . This study confirms the role of conditioning treatment as preferable in long term treatment of nocturnal enuresis . When this fails or when a safe drug with rapid effect is needed , however , desmopressin is a useful alternative OBJECTIVES To assess whether the synthetic vasopressin analogue desmopressin [ 1-desamino 8-D-arginine vasopressin ] is efficacious and safe in the management of nocturia + /- enuresis in patients with multiple sclerosis . PATIENTS AND METHODS Twenty-two women and 11 men , under 65 years of age , with clinical ly definite multiple sclerosis and nocturnal frequency + /- enuresis were entered into the study . A two week placebo run-in , to establish normal voiding patterns , followed by a double-blind , placebo-controlled , cross-over study of 20 micrograms intranasal desmopressin at night-time was carried out . RESULTS Desmopressin caused a significant decrease in nocturnal urinary frequency , nocturnal urinary volume and the percentage of total daily urine passed at night . There was no significant fall in plasma sodium with desmopressin although there were two cases of asymptomatic hyponatraemia . CONCLUSION Desmopressin is an efficacious and safe treatment for nocturia + /- enuresis in patients with multiple sclerosis The response of desamino-D-arginine vasopressin ( DDAVP ) was investigated in 32 enuretic children in a double-blind clinical study . The 15 children treated with DDAVP showed a significant reduction in the incidence of bed wetting -- from 18.7 + /- 6.5 to 6.5 + /- 9.2 wet nights per 30 days . In 6 children bed wetting stopped entirely , in 6 there was a satisfactory response , and in 3 the response was marginal or there was none . When DDAVP was stopped most children reverted to their earlier bedwetting habits ( 15.7 + /- 8.9 nights a month ) . Response to DDAVP was significantly better in children aged more than 10 years ( mean age for the entire group ) . The administration of DDAVP was not associated with any appreciable change in morning urine osmolalities . No adverse effects were noted . It is concluded that DDAVP is effective in nocturnal enuresis , particularly in older children . It is suggested that the cessation of bed wetting may , in part , reflect functional properties of DDAVP rather than antidiuresis To characterize the children with enuresis likely to respond to desmopressin acetate , we performed a double-blind crossover study that included the use of a placebo . During the two weeks of desmopressin administration , six children ( 12 % ) had 13 or 14 dry nights , and 15 children ( 29 % ) had eight to 12 dry nights . Among the 17 children aged 9 years or older , with four to seven dry nights during the two-week baseline period , 12 children ( 71 % ) responded to desmopressin ( eight to 14 dry nights ) . In contrast , none of the 15 children younger than 9 years of age with fewer than three dry nights before therapy responded . During the posttreatment period , only four of the 21 drug responders reported a persistent effect . Desmopressin may be effective in reducing the frequency of enuresis , especially in children older than 9 years of age without nightly enuresis During the period from March to September 1989 , 40 children suffering from primary nocturnal enuresis , aged between 5 and 14 years , were included in a study to assess the comparative therapeutical efficacy of DDAVP and acupuncture . Children were divided into four groups of 10 : group A was treated with DDAVP , group B was treated with acupuncture , group C was treated with DDAVP and acupuncture and group D was treated with placebo ( control ) . The trial design included 3 periods : observation ( 2 weeks ) , treatment ( 8 weeks ) and follow-up ( 4 weeks ) . Nineteen children completed the study . The efficacy of treatment , which was expressed as a percentage of dry nights , was high in both the DDAVP and acupuncture groups , when used separately . The combined treatment of DDAVP and acupuncture appeared to be the most efficacious both in terms of the percentage of dry nights at the end of treatment and in relation to the stability of results , even after the end of the study . The paper gives a detailed analysis of correlations between type of treatment and urinary osmolarity OBJECTIVE The aim of the study was to compare the efficacy and safety of different doses of DDAVP spray treatment ( 20 to 40 mcg/day ) in patients with primary monosymptomatic nocturnal enuresis ( defined as three or more wet nights per week ) . MATERIAL AND METHODS 237 patients ( 152 males , 75 females ; age range 5 - 17 years ) , with no infections or organic abnormalities of the urinary apparatus and no neurological disorders , were admitted into the trial . The experimental design was planned as an " open study " with five different treatments schedules ( 5 groups ) . The daily doses of DDAVP at bedtime in groups 1 and 2 were 20 and 30 mcg , respectively , for 6 weeks . In groups 3 and 4 the daily doses for the first 2 weeks were 20 and 30 mcg , respectively , and then , after a washout period of 2 weeks , the daily doses for the two groups were 30 and 20 mcg , respectively . A dose-response study ( 20 to 40 mcg/day ) was carried out in group 5 . RESULTS DDAVP spray therapy in primary monosymptomatic nocturnal enuresis was found to be resolutive in 70 - 75 % of treated patients . No difference in response was found between the patients treated with the daily dose of 20 and those on 30 mcg . No important reactions were observed in patients treated with DDAVP spray at the different daily dose ( 20 to 40 mcg ) or for different periods of time ( up to 6 weeks ) . CONCLUSIONS DDAVP spray therapy at a dose of 20 mcg/day was effective in 70 - 75 % of primary monosymptomatic nocturnal enuretics . In non-responders the daily dose of DDAVP should be increased to 30 to 40 mcg The effect of desamino-D-arginine vasopressin was investigated in a double-blind study of 37 children more than 9 years old with nocturnal enuresis resistant to conventional therapy . A significant reduction of wet nights was observed but as soon as the medication was stopped the children reverted to earlier bedwetting habits PURPOSE Desmopressin nasal spray has proved to be efficacious treatment of primary nocturnal enuresis . Oral desmopressin tablets would be a more easily used , convenient vehicle for our patients and their parents . We evaluated the effectiveness of oral desmopressin in decreasing the number of wet nights in patients with primary nocturnal enuresis . MATERIAL S AND METHODS We performed a double-blind , placebo controlled , parallel group trial of oral desmopressin in 141 children 5 to 17 years old with documented primary nocturnal enuresis at 14 sites . Patients were screened for number of wet nights for 2 weeks before study entry . A minimum of 3 wet nights weekly for 2 consecutive weeks was required for study entry . Patients were r and omized to receive 200 , 400 or 600 mcg . desmopressin or placebo before bedtime . Fluids were restricted 2 hours before bedtime based on body weight . The primary efficacy variable was mean decrease in the number of wet nights recorded during the last 2-week treatment period . The percentage of responding patients and mean decrease from baseline in number of wet nights at 2 , 4 and 6 weeks were also assessed . RESULTS The decrease in wet nights was 9 , 20 , 30 and 36 % for placebo , and 200 , 400 , and 600 mcg . desmopressin orally per day , respectively . The 600 mcg . dose of oral desmopressin daily was statistically significantly different ( p < 0.05 ) from placebo in decreasing wet nights . A complete or near complete response ( 0 to 2 wet nights ) was noted in 3 , 18 , 33 and 24 % of the patients who received placebo , and 200 , 400 and 600 mcg . oral desmopressin daily , respectively . The 400 and 600 mcg . treatment groups were statistically significantly different ( p < 0.05 ) from placebo . A less than 50 % decrease in wet nights was noted in 83 , 79 , 64 and 61 % of the patients who received placebo , and 200 , 400 and 600 mcg . oral desmopressin daily , respectively . Oral desmopressin exhibited a dose response in the treatment of primary nocturnal enuresis . The linear trend for the decrease in wet nights was statistically significant ( p < 0.05 ) . CONCLUSIONS A dose of 600 mcg . oral desmopressin daily significantly decreased the mean number of wet nights when administered for 6 weeks . A higher dose may be necessary for an improved response PURPOSE The use of desmopressin in patients with primary nocturnal enuresis is based on the hypothesis of a nocturnal lack of endogenous arginine vasopressin . However , in addition to the kidney , other targets of desmopressin are known . Therefore , we examined whether the administration of desmopressin influences central nervous function in children with primary nocturnal enuresis . MATERIAL S AND METHODS Our prospect i ve , r and omized , double-blind , placebo controlled cross-over study was performed on 40 children with nocturnal enuresis . Patients were r and omly assigned to receive either 20 microg . desmopressin intranasally or 0.9 % saline solution . Each group comprised 19 and 21 to children , respectively . After 2 weeks the groups were switched . The children were tested for short-term memory and reaction time to both treatments . Statistical analysis was done using the Wilcoxon matched pairs test . RESULTS Median patient age was 8.0 years ( range 6 to 13 ) . During desmopressin treatment children in both groups had a significant decrease of wet nights ( 5. Output:	Amitriptyline ( another tricyclic ) was not consistently better than desmopressin either alone or when used as a supplement . Combining alarm and drug therapy was found to be superior to alarm treatment alone . REVIEW ER 'S CONCLUSIONS Desmopressin rapidly reduced the number of wet nights per week , but there was some evidence that this was not sustained after treatment stopped . Comparison with alternative treatments suggested that desmopressin and tricyclics had similar clinical effects , but that alarms produced more sustained benefits . However , the risk of water intoxication associated with over-drinking before bedtime has been reported .
MS21284	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Abstract Objective : To evaluate the use of a computerised support system for decision making for implementing evidence based clinical guidelines for the management of asthma and angina in adults in primary care . Design : A before and after pragmatic cluster r and omised controlled trial utilising a two by two incomplete block design . Setting : 60 general practice s in north east Engl and . Participants : General practitioners and practice nurses in the study practice s and their patients aged 18 or over with angina or asthma . Main outcome measures : Adherence to the guidelines , based on review of case notes and patient reported generic and condition specific outcome measures . Results : The computerised decision support system had no significant effect on consultation rates , process of care measures ( including prescribing ) , or any patient reported outcomes for either condition . Levels of use of the software were low . Conclusions : No effect was found of computerised evidence based guidelines on the management of asthma or angina in adults in primary care . This was probably due to low levels of use of the software , despite the system being optimised as far as was technically possible . Even if the technical problems of producing a system that fully supports the management of chronic disease were solved , there remains the challenge of integrating the systems into clinical encounters where busy practitioners manage patients with complex , multiple conditions UNLABELLED Critics of the use of clinical practice guidelines ( CPGs ) in an emergency department ( ED ) setting believe that they are too cumbersome and time-consuming , but to the best of the authors ' knowledge , potential barriers to CPG adherence in the ED have not been prospect ively evaluated . OBJECTIVES To measure provider adherence to an ED CPG based on National Asthma Education and Prevention Program ( NAEPP ) recommendations , and to determine factors associated with provider nonadherence . METHODS Prospect i ve , cohort study of children aged 1 - 18 years with the diagnosis of an acute exacerbation of asthma who were seen in a pediatric ED and requiring admission , as well as a r and om selection of children discharged to home following pediatric ED care . The following adherence parameters were assessed : at least three nebulized albuterol treatments in the first hour ; early steroid administration ( after the first nebulizer treatment ) ; clinical assessment s using pulse oximetry and peak expiratory flow ( PEF ) ( for children > 6 years old ) ; and use of a clinical score to assess acute illness severity ( Asthma Severity Score ) . Nonadherence was defined as any deviation of the above parameters . RESULTS Between July 1 , 1998 , and June 30 , 1999 , 369 patients were studied . Of these , 38 % ( 139 ) were discharged to home , 38 % ( 140 ) were admitted to the observation unit , and 24 % ( 90 ) were admitted to the inpatient unit . Illness severities at initial presentation to the ED were : 24 % ( 86 ) had mild exacerbations , 59 % ( 212 ) had moderate exacerbations , and 17 % ( 62 ) had severe exacerbations . Sixty-eight percent ( 95 % CI = 63 % to 73 % ) of the patients were managed with complete adherence to the CPG . Of the 32 % with some form of nonadherence , most ( 63 % ) were children older than 6 years ; in this group 64 % ( 48/75 ) were nonadherent due to lack of PEF assessment . When PEF assessment was disregarded , an 83 % ( 95 % CI = 79 % to 87 % ) adherence to the CPG was achieved . Other nonadherence factors included : lack of at least three nebulized albuterol treatments provided timely within the first hour ( 5 % ) ; delay in steroid administration ( 6 % ) ; lack of pulse oximeter use ( 0.5 % ) ; and failure to record clinical score to assess severity ( 1.1 % ) . Patient age , illness severity ( acute and chronic ) , first episode of wheezing , and high ED volume periods ( evenings and weekends ) did not worsen adherence . CONCLUSIONS Clinical practice guidelines can be used successfully in the pediatric ED and provide a more efficient management and treatment approach to acute exacerbations of childhood asthma . With a systematic and concise CPG , barriers to adherence in a pediatric ED appear to be minimal , with the exception of using PEF in the routine ED assessment 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 This prospect i ve study was design ed to determine whether incorporating formoterol into a st and ardized respiratory therapist-directed protocol for administering bronchodilators to hospitalized patients with obstructive airway disease would reduce health care re source use and provide a safety advantage . All patients admitted to Washington Hospital Center with asthma and chronic obstructive pulmonary disease ( CODP ) are administered bronchodilators under a st and ardized respiratory therapist-directed protocol . Formoterol was the primary bronchodilator for the intervention period from January through March 2002 , with levalbuterol , albuterol , and ipratropium available as needed . Results for the intervention period were compared against two historical control periods . From January through March 2000 , the bronchodilators in the protocol were albuterol and ipratropium , and from January through March 2001 levalbuterol , albuterol , and ipratropium were available . Health care re source use was determined by the number of bronchodilator treatments administered per admission . Costs ( adjusted to 2002 dollars ) for supplies , therapist time , and drugs were calculated for the three time periods . Adverse events related to bronchodilator administration were recorded in a st and ardized manner for all three time periods . Bronchodilator treatments per admission , respiratory therapist visits per admission , and time spent per admission , and cost per bronchodilator treatment significantly decreased in 2002 . Significantly fewer adverse events related to bronchodilator treatments were reported in 2002 than 2000 . The addition of formoterol to a respiratory therapist-directed protocol for administering bronchodilators reduced health care re source use and adverse events for patients with asthma and COPD 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 Little is known about the impact of implementing nursing-oriented best practice guidelines on the delivery of patient care in either hospital or community setting s. Methods A naturalistic study with a prospect i ve , before and after design documented the implementation of six newly developed nursing best practice guidelines ( asthma , breastfeeding , delirium-dementia-depression ( DDD ) , foot complications in diabetes , smoking cessation and venous leg ulcers ) . Eleven health care organisations were selected for a one-year project . At each site , clinical re source nurses ( CRNs ) worked with managers and a multidisciplinary steering committee to conduct an environmental scan and develop an action plan of activities ( i.e. education sessions , policy review ) . Process and patient outcomes were assessed by chart audit ( n = 681 pre-implementation , 592 post-implementation ) . Outcomes were also assessed for four of six topics by in-hospital/home interviews ( n = 261 pre-implementation , 232 post-implementation ) and follow-up telephone interviews ( n = 152 pre , 121 post ) . Interviews were conducted with 83/95 ( 87 % ) CRN 's , nurses and administrators to describe recommendations selected , strategies used and participants ' perceived facilitators and barriers to guideline implementation . Results While statistically significant improvements in 5 % to 83 % of indicators were observed in each organization , more than 80 % of indicators for breastfeeding , DDD and smoking cessation did not change . Statistically significant improvements were found in > 50 % of indicators for asthma ( 52 % ) , diabetes foot care ( 83 % ) and venous leg ulcers ( 60 % ) . Organizations with > 50 % improvements reported two unique implementation strategies which included h and s-on skill practice sessions for nurses and the development of new patient education material s. Key facilitators for all organizations included education sessions as well as support from champions and managers while key barriers were lack of time , workload pressure and staff resistance . Conclusion Implementation of nursing best practice guidelines can result in improved practice and patient outcomes across diverse setting s yet many indicators remained unchanged . Mobilization of the nursing workforce to actively implement guidelines and to monitor the delivery of their care is important so that patients may learn about and receive recommended healthcare Objective . To evaluate effects on the process and outcomes of care brought about by use of a h and held , computer-based system that implements the American Academy of Pediatrics guideline on office management of asthma exacerbations . Design . A before – after trial with r and omly selected , office-based Connecticut pediatricians . In both the control and intervention phases , physicians collected data from 10 patient encounters for acute asthma exacerbations . During the intervention phase , the computer provided for structured encounter documentation and offered recommendations based on the guideline of the American Academy of Pediatrics . Patients were contacted by telephone 7 to 14 days after the visit to assess outcomes . Results . Nine study -physicians enrolled 91 patients in the control phase and 74 in the intervention phase . Follow-up information was available for 93 % of encounters . Use of the intervention was associated with increased mean frequency/visit of : 1 ) measurements of peak expiratory flow rate ( 2.18 vs 1.57 ) and oxygen saturation ( 1.12 vs .42 ) , and 2 ) administration of nebulized β2-agonists ( 1.25 vs .71 ) . Visits in the intervention phase lasted longer and fees were higher ( $ 145.61 vs $ 103.11 ) . There were no significant differences in immediate disposition or subsequent emergency department visits , hospitalizations , missed school , or caretaker Output:	Paper-based reminders were the most frequent with fully computerized , then computer generated , and other modalities . No study reported a decrease in health care practitioner performance or declining patient outcomes . The most common primary outcome measure was compliance with provided or prescribing guidelines , key clinical indicators such as patient outcomes or quality of life , and length of stay . Conclusions Paper-based implementations are by far the most popular approach to implement a guideline or protocol . Asthma guidelines generally improved patient care and practitioner performance regardless of the implementation method
MS21285	*TASK* the task is to summarize an input biomedical literature in six sentences *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 management of depression in patients with poor prognosis cancers , such as lung cancer , creates specific challenges . We aim ed to assess the efficacy of an integrated treatment programme for major depression in patients with lung cancer compared with usual care . METHODS Symptom Management Research Trials ( SMaRT ) Oncology-3 is a parallel-group , multicentre , r and omised controlled trial . We enrolled patients with lung cancer and major depression from three cancer centres and their associated clinics in Scotl and , UK . Participants were r and omly assigned in a 1:1 ratio to the depression care for people with lung cancer treatment programme or usual care by a data base software algorithm that used stratification ( by trial centre ) and minimisation ( by age , sex , and cancer type ) with allocation concealment . Depression care for people with lung cancer is a manualised , multicomponent collaborative care treatment that is systematic ally delivered by a team of cancer nurses and psychiatrists in collaboration with primary care physicians . Usual care is provided by primary care physicians . The primary outcome was depression severity ( on the Symptom Checklist Depression Scale [ SCL-20 ] , range 0 - 4 ) averaged over the patient 's time in the trial ( up to a maximum of 32 weeks ) . Trial statisticians and data collection staff were masked to treatment allocation , but patients and clinicians could not be masked to the allocations . Analyses were by intention to treat . This trial is registered with Current Controlled Trials , number IS RCT N75905964 . FINDINGS 142 participants were recruited between Jan 5 , 2009 , and Sept 9 , 2011 ; 68 were r and omly allocated to depression care for people with lung cancer and 74 to usual care . 43 ( 30 % ) of 142 patients had died by 32 weeks , all of which were cancer-related deaths . No intervention-related serious adverse events occurred . 131 ( 92 % ) of 142 patients provided outcome data ( 59 in the depression care for people with lung cancer group and 72 in the usual care group ) and were included in the intention-to-treat primary analysis . Average depression severity was significantly lower in patients allocated to depression care for people with lung cancer ( mean score on the SCL-20 1·24 [ SD 0·64 ] ) than in those allocated to usual care ( mean score 1·61 [ SD 0·58 ] ) ; difference -0·38 ( 95 % CI -0·58 to -0·18 ) ; st and ardised mean difference -0·62 ( 95 % CI -0·94 to -0·29 ) . Self-rated depression improvement , anxiety , quality of life , role functioning , perceived quality of care , and proportion of patients achieving a 12-week treatment response were also significantly better in the depression care for people with lung cancer group than in the usual care group . INTERPRETATION Our findings suggest that major depression can be treated effectively in patients with a poor prognosis cancer ; integrated depression care for people with lung cancer was substantially more efficacious than was usual care . Larger trials are now needed to estimate the effectiveness and cost-effectiveness of this care programme in this patient population , and further adaptation of the treatment will be necessary to address the unmet needs of patients with major depression and even shorter life expectancy . FUNDING Cancer Research UK and Chief Scientist Office of the Scottish Government In the context of chronic physical illness , such as breast cancer , depression is associated with increased morbidity , longer periods of hospitalization , and greater overall disability . Prompt diagnosis and effective treatment is , therefore , essential . Several small studies have established the efficacy of tricyclic antidepressants ( TCAs ) in this setting , and the selective serotonin reuptake inhibitors ( SSRIs ) would appear to be an alternative therapeutic option because of their established efficacy and better tolerability profile . This was a multicenter , double-blind , parallel-group study in which 179 women with breast cancer were r and omized to treatment with either the SSRI paroxetine ( 20–40mg/day ) , or the TCA , amitriptyline ( 75–150mg/day ) . After 8-weeks treatment , depressive symptomatology had improved markedly and to a similar extent in both groups on the Montgomery Asberg Depression Rating Scale . Clinical global impression ( CGI ) Global improvement and Patient global evaluation scales indicated that patients were minimally to much improved at study endpoint ; a change from moderately/mildly ill to borderline ill on the CGI severity of Illness scale . A steady improvement in quality of life was also observed in both groups . There were no clinical ly significant differences between the groups . In total , 47 ( 53.4 % ) patients in the paroxetine group and 53 ( 59.6 % ) patients in the amitriptyline group had adverse experiences , the most common of which were the well-recognized side-effects of the antidepressant medications or chemotherapy . Anticholinergic effects were almost twice as frequent in the amitriptyline group ( 19.1 % ) compared with paroxetine ( 11.4 % ) . This study has demonstrated that paroxetine is a suitable alternative to amitriptyline for the treatment of depression in patients with breast cancer Little has been done to study the effectiveness of antidepressants in controlling anxiety/depression in a population of cancer patients . A double‐blind placebo‐controlled study was therefore design ed to assess the effectiveness of 20 mg fluoxetine . Of 115 cancer patients who fulfilled entry criteria for levels of distress , 45 patients were r and omized to a fluoxetine treatment group ( FA ) and 46 patients to a placebo group ( PA ) after a 1‐week placebo period design ed to exclude placebo responders . The Montgomery and Asberg Depression Scale ( MADRS ) , the Hamilton Anxiety Scale ( HAS ) , the Hospital Anxiety and Depression Scale ( HADS ) , the Revised Symptom Checklist ( SCL90‐R ) and the Spitzer Quality of Life Index ( SQOLI ) were used to assess the efficacy of fluoxetine . The response rate , defined by a HADS score lower than 8 after 5 weeks of treatment , was not significantly higher in the FA group ( 11 % ) compared to the PA group ( 7 % ) . Compared to the PA group , patients in the FA group showed a significantly greater decrease in SCL90‐R mean total score after 5 weeks , but not a greater decrease in HADS mean score . No difference between the two groups was found in observer‐reported assessment s ( MADRS , HAS and SQOLI ) . Significantly more drop‐outs were observed in the FA group ( n=15 ) than in the PA group ( n=7 ) , although the frequencies of side‐effects were not significantly different BACKGROUND There is a lack of trials of psychodynamic treatments of depression in breast cancer patients . The purpose of this trial was to determine the efficacy of short-term psychodynamic psychotherapy ( STPP ) in non-metastatic breast cancer patients diagnosed with depression , one of the most frequent mental comorbidities of breast cancer . PATIENTS AND METHODS In a multicenter prospect i ve trial , 157 breast cancer patients with comorbid depression were r and omized to either individual STPP ( intervention group , N=78 ) or ' treatment as usual ' ( control group , TAU , N=79 ) . As our primary outcome measure , we hypothesized a higher rate of remission defined as no diagnosis of depression ( Structured Clinical Interview for DSM-IV ) and reduction in depression score by at least 2 points ( Hospital Anxiety and Depression Scale , HADS-D ) in STPP versus TAU at treatment termination . Secondary outcomes mainly refer to quality of life ( QoL ) . RESULTS In the intention to treat ( ITT ) analysis , 44 % of the STPP group achieved highly significantly more remission than TAU ( 23 % ) . STPP treatment ( OR=7.64 ; P<0.001 ) was the strongest predictor for remission post-treatment ; time was also significant ( OR=0.96 ; P<0.05 ) . A high effect favoring STPP ( d=0.82 ) was observed for the HADS-D score post-treatment ( secondary outcome ) . Regarding further secondary outcomes ( QoL ) , analyses of covariance yielded main effects for group ( favoring STPP with an effect size of at least d=0.5 ) for global QoL , role , emotional and social functioning , pain , treatment side-effects , breast symptoms and upset by hair loss . CONCLUSIONS STPP is an effective treatment of a broad range of depressive conditions in breast cancer patients improving depression and functional QoL. Findings are limited by the drop-out rate ( ∼1/3 ) and delayed post-treatment assessment s. Future trials may consider stepped-care approaches , tailored to patients ' needs and requirements in the acute treatment phase OBJECTIVE Head and neck cancer ( HNC ) patients have a high incidence of cancer-related posttraumatic stress disorder ( PTSD ) and other anxiety and depressive disorders . We report the results from the first pilot r and omized controlled trial in which the efficacy of an early cognitive-behavioral therapy ( CBT ) program was compared with a non-directive supportive counseling ( SC ) intervention in reducing PTSD , general anxiety and depressive symptoms , and improving perceived quality of life in newly diagnosed , distressed HNC patients undergoing radiotherapy . PATIENTS AND METHODS Thirty-five HNC patients ( mean age=54.8 years ; 80 % males ) with elevated levels of PTSD , depression or anxiety were r and omized to seven individual sessions of a multi-modal CBT or non-directive SC , concurrent with patients ' radiotherapy . The SC intervention provided non-directive counseling support . PTSD , anxiety and depressive symptoms ( primary outcomes ) , and cancer-related appraisal s and quality of life ( secondary outcomes ) were assessed pre-intervention ( baseline ) , 1 month , 6 months and 12 months post-intervention by diagnostic clinical interviews and vali date d self-report question naires . RESULTS The CBT and SC interventions were found to be equal in their effects in reducing PTSD and anxiety symptoms both in the short and longer term . However , up to 67 % of patients in the CBT program no longer met clinical or sub- clinical PTSD , anxiety and /or depression by 12 months post-treatment compared with 25 % of patients who received SC . CONCLUSION Findings indicate that the early provision of psychotherapy has utility in reducing PTSD , anxiety and depressive symptoms , and preventing chronic psychopathology in distressed HNC patients Background Depression is common among older cancer patients , but little is known about the optimal approach to caring for this population . This analysis evaluates the effectiveness of the Improving Mood-Promoting Access to Collaborative Treatment ( IMPACT ) program , a stepped care management program for depression in primary care patients who had an ICD-9 cancer diagnosis . Methods Two hundred fifteen cancer patients were identified from the 1,801 participants in the parent study . Subjects were 60 years or older with major depression ( 18 % ) , dysthymic disorder ( 33 % ) , or both ( 49 % ) , recruited from 18 primary care clinics belonging to 8 health-care organizations in 5 states . Patients were r and omly assigned to the IMPACT intervention ( n = 112 ) or usual care ( n = 103 ) . Intervention patients had access for up to 12 months to a depression care manager who was supervised by a psychiatrist and a primary care provider and who offered education , care management , support of antidepressant management , and brief , structured psychosocial interventions including behavioral activation and problem-solving treatment . Results At 6 and 12 months , 55 % and 39 % of intervention patients had a 50 % or greater reduction in depressive symptoms ( SCL-20 ) from baseline compared to 34 % and 20 % of usual care participants ( P = 0.003 and P = 0.029 ) . Intervention patients also experienced greater remission rates ( P = 0.031 ) , more depression-free days ( P < 0.001 ) , less functional impairment ( P = 0.011 ) , and greater quality of life ( P = 0.039 ) at 12 months than usual care participants . Conclusions The IMPACT collaborative care program appears to be feasible and effective for depression among older cancer patients in diverse primary care setting 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 Major depressive disorder severely impairs the quality of life of patients with medical disorders such as cancer , but evidence to guide its management is scarce . We aim ed to assess the efficacy and cost of a nurse-delivered complex intervention that was design ed to treat major depressive disorder in patients who have cancer . METHODS We did a r and omised trial in a regional cancer centre in Scotl and , UK . 200 out patients who had cancer with a prognosis of greater than 6 months and major depressive disorder ( identified by screening ) were eligible and agreed to take part . Their mean age was 56.6 ( SD 11.9 ) years , and 141 ( 71 % ) were women . We r and omly assigned 99 of these participants to usual care , and 101 to usual care plus the intervention , with minimisation for sex , age , diagnosis , and extent of disease . The intervention was delivered by a cancer nurse at the centre over an average of seven sessions . The primary outcome was the difference in mean score on the self-reported Symptom Checklist-20 depression scale ( range Output:	The recommendations and practical management tools were review ed as being well organized and helpful , although systemic barriers to implementation were identified . This up date d guideline supports the previous general recommendation that patients with cancer who have depression may benefit from psychological and /or pharmacologic interventions , without evidence for the superiority of any specific treatment over another .
MS21286	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Comparison of Reverse Foam Sclerotherapy of the great saphenous vein ( GSV ) combed with sapheno-femoral junction ( SFJ ) ligation to st and ard ( Babcock ) stripping and invagination ( Pin ) stripping in a prospect i ve clinical series . DESIGN Prospect i ve clinical series . MATERIAL S AND METHODS 90 consecutive limbs of 82 patients with incompetence of the GSV result ing in varicose veins were prospect ively r and omised into 3 groups of 30 , treated by SFJ ligation and either reverse foam sclerotherapy , st and ard stripping or invagination stripping of the GSV . Outcomes were assessed post-operatively and at 2-weeks follow-up . Peri-operative blood loss ( 24 hrs ) , analgesic requirement , bruising and residual varicosities were assessed . Bruising was assessed by both patients and independent assessors using question naires . RESULTS SFJ ligation plus reverse foam sclerotherapy of the GSV was associated with significantly less blood loss , bruising and post-op discomfort than either of the stripping techniques . ( p<0.001 , Mann-Whitney ) CONCLUSION St and ard stripping of the GSV and invagination stripping are not associated with major discomfort and problems in the early post-operative period . SFJ ligation and GSV reverse foam sclerotherapy yielded greater patient satisfaction with less post-op bruising and discomfort and reduced analgesic requirements Endovenous laser ablation ( EVLA ) and radiofrequency ablation ( RFA ) are both associated with excellent technical , clinical and patient‐reported outcomes for the treatment of varicose veins . The aim of this study was to compare the techniques in a r and omized clinical trial OBJECTIVES To assess the quality of life of patients undergoing sapheno-femoral junction ( SFJ ) ligation and long saphenous vein stripping ( LSV ) , using two different techniques . DESIGN Prospect i ve , r and omised trial . MATERIAL S AND METHODS Eighty patients were recruited and r and omised to either Perforate Invagination ( PIN ) stripping ( 43 ) or Conventional stripping ( 37 ) . Patients completed the Short Form 36 ( SF-36 ) and EuroQol ( EQ ) question naires preoperatively , and postoperatively at 6 weeks and 6 months . RESULTS Bodily pain , role function and physical summary were significantly improved at 6 months in the PIN stripping group . In the Conventional group , bodily pain and physical function were similarly improved , but not role function . EQ global quality of life was significantly and progressively improved at 6 weeks and 6 months in the PIN group ( global score p<0.003 ; self-rated score p < 0.001 ) . In the Conventional group there was no overall improvement in global score or self-rated health . CONCLUSIONS Primary varicose vein surgery is associated with significant and progressive improvements in quality of life scores . Whilst overall quality of health does improve in the Conventional group , this appears to be to a lesser extent than in the PIN group BACKGROUND Although endovenous laser ablation for varicose veins is replacing surgical stripping , proper economic evaluation with adequate follow-up in a r and omised clinical trial is important for considered policy decisions regarding the implementation of new techniques . METHODS Data from a r and omised controlled trial comparing cryostripping and endovenous laser ablation in 120 patients were combined to study Short Form ( SF ) 6D outcome , costs and cost-effectiveness 2 years after treatment . Incremental cost per quality -adjusted life year ( QALY ) gained 2 years after treatment was calculated using different strategies , and uncertainty was assessed with bootstrapping . RESULTS Over the total study period , mean SF-6D scores improved slightly from 0.78 at baseline to 0.80 at 2 years for patients who underwent cryostripping and from 0.77 to 0.79 for patients who underwent endovenous laser . QALY ( SF-6D ) was 1.59 in patients who underwent cryostripping and 1.60 in patients who underwent endovenous laser 2 years after treatment . The costs of cryostripping and endovenous laser per patient were euro 2651 and euro 2783 , respectively . Bootstrapping indicated that cryostripping was associated with an incremental cost-effectiveness ratio of euro 32 per QALY gained . With regard to different strategies , outpatient cryostripping was less costly and more effective 2 years after treatment . CONCLUSION In this study , in terms of costs per QALY gained , outpatient cryostripping appeared to be the dominant strategy , but endovenous laser yielded comparable outcomes for a relatively little additional cost OBJECTIVES Comparison of sapheno-femoral ligation and stripping ( SFL/S ) versus endovenous laser ablation ( EVLA , 980-nm ) in the treatment of great saphenous vein ( GSV ) insufficiency , using local tumescent anaesthesia . DESIGN R and omised , single centre trial . MATERIAL S AND METHODS Patients with GSV incompetence and varicose veins were r and omised to either SFL/S or EVLA . At days 1 , 2 , 3 , 7 , 10 , and 14 post-treatment , patients completed question naires on pain and quality of life . Recurrent varicose veins were evaluated by Duplex ultrasound ( DUS ) performed at 1 and 6 weeks , and 6 and 12 months . RESULTS 130 legs in 121 patients were treated by SFL/S ( n=68 ) or EVLA ( n=62 ) . Significantly more post-treatment pain was noted after EVLA at days 7 , 10 and 14 ( p<0.01 ; p<0.01 ; p=0.01 ) , more hindrance in mobility at days 7 ( p<0.01 ) and 10 ( p=0.01 ) , and in self care ( p=0.03 ) and daily activities ( p=0.01 ) at day 7 compared to SFL/S. DUS at 1-year follow-up showed 9 % recurrences ( 5/56 ) after EVLA and 10 % ( 5/49 ) after SFL/S. CONCLUSION Both SFL/S and EVLA , using local tumescent anaesthesia , were well tolerated , with no difference in short-term recurrence rate . In the second week after EVLA , patients experienced significantly more pain result ing in restricted mobility , self care and daily activity compared to Introduction : Chronic venous insufficiency is the most common vascular disease in the adult population . However , r and omized clinical trials ( RCTs ) comparing therapeutic options are limited . Patients and Methods : A total of 180 patients with saphenofemoral junction and great saphenous reflux detected on duplex were r and omized to either ultrasound-guided radiofrequency ablation ( RFA ) or st and ard surgical treatment . The study participants blindly chose an assignment card that placed them in either group A ( ultrasound-guided RFA of the great saphenous vein [ GSV ] ; n = 90 ) ; or group B ( surgical management n = 90 ) . Patients were followed up for 24 months . Results : The primary occlusion rate in group A was 94.5 % versus 100 % in group B. Radiofrequency ablation had a lower overall complication rate ( P = .02 ) and shorter post-intervention hospital stay ( P = .001 ) . Kaplan-Meier analysis showed no significant differences in recurrence rates at 24 months follow-up ( P = .45 ) . Radiofrequency ablation was significantly more expensive ( P = .003 ) . Conclusion : Great saphenous vein occlusion was achieved efficiently in 94 % of our group using RFA with minimal complications and obvious advantages as compared to st and ard surgery INTRODUCTION This study compares the outcome 3 years after treatment of varicose veins by endovenous laser ablation ( EVLA ) , radiofrequency ablation , ultrasound-guided foam sclerotherapy ( UGFS ) , or surgery by assessing recurrence , Venous Clinical Severity Score ( VCSS ) , and quality of life ( QOL ) . METHODS A total of 500 patients ( 580 legs ) were r and omized to one of the three endovenous treatments or high ligation and stripping of the great saphenous vein ( GSV ) . Follow-up included clinical and duplex ultrasound examinations and VCSS and QOL question naires . Kaplan-Meier ( KM ) life-table analysis was used . P values below .05 were considered statistically significant . RESULTS At 3 years , eight ( KM estimate , 7 % ) , eight ( KM estimate , 6.8 % ) , 31 ( KM estimate , 26.4 % ) , and eight ( KM estimate , 6.5 % ) of GSVs recanalized or had a failed stripping procedure ( more than 10 cm open refluxing part of the treated GSV ; CLF , EVLA , UGFS , and stripping , respectively ; P < .01 ) . Seventeen ( KM estimate , 14.9 % ) , 24 ( KM estimate , 20 % ) , 20 ( KM estimate , 19.1 % ) , and 22 ( KM estimate , 20.2 % ) legs developed recurrent varicose veins ( P = NS ) . The patterns of reflux and location of recurrent varicose veins were not different between the groups . Within 3 years after treatment , 12 ( KM estimate , 11.1 % ) , 14 ( KM estimate , 12.5 % ) , 37 ( KM estimate , 31.6 % ) , and 18 ( KM estimate , 15.5 % ) legs were retreated in the CLF , EVLA , UGFS , and stripping groups , respectively ( P < .01 ) . VCSS , SF-36 , and Aberdeen QOL scores improved significantly in all the groups with no difference between the groups . CONCLUSIONS All treatment modalities were efficacious and result ed in a similar improvement in VCSS and QOL . However , more recanalization and reoperations were seen after UGFS Endovenous laser ablation ( EVLA ) is a popular minimally invasive treatment for varicose veins . Surgical treatment , featuring junctional ligation and inversion stripping , has shown excellent clinical and cost effectiveness . The clinical effectiveness of both treatments was compared within a r and omized trial BACKGROUND Great saphenous vein ( GSV ) incompetence is the most common cause of superficial venous insufficiency . Radiofrequency catheter ablation ( RFA ) is superior to conventional ligation and stripping , and endovenous laser treatment ( EVL ) has emerged as an effective alternative to RFA . This r and omized study evaluated RFA and EVL for superficial venous insufficiency due to GSV incompetence and compared early and 1-year results . METHODS Between June 2006 and May 2008 , patients with symptomatic primary venous insufficiency due to GSV incompetence were r and omized to RFA or EVL . Patients with bilateral disease were r and omized for treatment of the first leg and received the alternative method on the other . Pretreatment examination included a leg assessment using the Venous Clinical Severity Score ( VCSS ) and CEAP classification . Patients completed the Chronic Venous Insufficiency Question naire 2 ( CIVIQ2 ) . RFA was performed with the ClosurePlus system ( VNUS Medical Technologies , Sunnyvale , Calif ) . EVL was performed with the EVLT system ( AngioDynamics Inc , Queensbury , NY ) . Early ( 1-week and 1-month ) postoperative results of pain , bruising , erythema , and hematoma were recorded . Duplex ultrasound ( DU ) imaging was used at 1 week and 1 year to evaluate vein status . VCSS scores and CEAP clinical class were recorded at each postoperative visit , and quality of life ( QOL ) using CIVIQ2 was assessed at 1 month and 1 year . RESULTS The study enrolled 118 patients ( 141 limbs ) : 46 ( 39 % ) were r and omized to RFA and 48 ( 40 % ) to EVL , and 24 ( 20 % ) had bilateral GSV incompetence . At 1 week , one patient in the RFA group had an open GSV and was deemed a failure . More bruising occurred in the EVL group ( P = .01 ) at 1 week , but at 1 month , there was no difference in bruising between groups . At 1 year , DU imaging showed evidence of recanalization with reflux in 11 RFA and 2 EVL patients ( P = .002 ) . The mean VCSS score change from baseline to 1 week postprocedure was higher for RFA than EVL ( P = .002 ) , but there was no difference between groups at 1 month ( P = .07 ) and 1 year ( P = .9 ) . Overall QOL mean score improved over time for all patients ( P < .001 ) . CEAP clinical class scores of > or=3 were recorded in 21 RFA ( 44 % ) and 24 EVL patients ( 44 % ) pretreatment , but at 1-year , 9 RFA ( 19 % ) and 12 EVL patients ( 24 % ) had scores of > or=3 ( P < .001 ) . This represented a significant improvement in all patients compared with baseline . CONCLUSION Both methods of endovenous ablation effectively reduce symptoms of superficial venous insufficiency . EVL is associated with greater Output:	Differences between treatments were negligible in terms of clinical outcomes , so the treatment with the lowest cost appears to be most cost-effective . Total FS costs were estimated to be lowest , and FS was marginally more effective than surgery . However , relative effectiveness was sensitive to the model time horizon . Threshold analysis indicated that EVLA and RFA might be considered cost-effective if their costs were similar to those for surgery . This assessment of currently available evidence suggests there is little to choose between surgery and the minimally invasive techniques in terms of efficacy or safety , so the relative cost of the treatments becomes one of the deciding factors .
MS21287	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Artemether-lumefantrine ( AL ) was adopted as first-line treatment for uncomplicated malaria in Kenya in 2006 . Monitoring drug efficacy at regular intervals is essential to prevent unnecessary morbidity and mortality . The efficacy of AL and dihydroartemisinin-piperaquine ( DP ) were evaluated for the treatment of uncomplicated malaria in children aged six to 59 months in western Kenya . Methods From October 2010 to August 2011 , children with fever or history of fever with uncomplicated Plasmodium falciparum mono-infection were enrolled in an in vivo efficacy trial in accordance with World Health Organization ( WHO ) guidelines . The children were r and omized to treatment with a three-day course of AL or DP and efficacy outcomes were measured at 28 and 42 days after treatment initiation . Results A total of 137 children were enrolled in each treatment arm . There were no early treatment failures and all children except one had cleared parasites by day 3 . Polymerase chain reaction (PCR)-uncorrected adequate clinical and parasitological response rate ( ACPR ) was 61 % in the AL arm and 83 % in the DP arm at day 28 ( p = 0.001 ) . PCR-corrected ACPR at day 28 was 97 % in the AL group and 99 % in the DP group , and it was 96 % in both arms at day 42 . Conclusions AL and DP remain efficacious for the treatment of uncomplicated malaria among children in western Kenya . The longer half-life of piperaquine relative to lumefantrine may provide a prophylactic effect , accounting for the lower rate of re-infection in the first 28 days after treatment in the DP arm Background Co-infection with malaria and intestinal parasites such as Ascaris lumbricoides is common . Malaria parasites induce a pro-inflammatory immune response that contributes to the pathogenic sequelae , such as malarial anaemia , that occur in malaria infection . Ascaris is known to create an anti-inflammatory immune environment which could , in theory , counteract the anti-malarial inflammatory immune response , minimizing the severity of malarial anaemia . This study examined whether Ascaris co-infection can minimize the severity of malarial anaemia . Methods Data from a r and omized controlled trial on the effect of antihelminthic treatment in Nigerian preschool-aged ( 6–59 months ) children conducted in 2006–2007 were analysed to examine the effect of malaria and Ascaris co-infection on anaemia severity . Children were enrolled and tested for malaria , helminths and anaemia at baseline , four , and eight months . Six hundred and ninety subjects were analysed in this study . Generalized linear mixed models were used to assess the relationship between infection status and Ascaris and Plasmodium parasite intensity on severity of anaemia , defined as a haemoglobin less than 11 g/dL. Results Malaria prevalence ranged from 35 - 78 % over the course of this study . Of the malaria-infected children , 55 % were co-infected with Ascaris at baseline , 60 % were co-infected four months later and 48 % were co-infected eight months later , underlining the persistent prevalence of malaria-nematode co-infections in this population . Over the course of the study the percentage of anaemic subjects in the population ranged between 84 % at baseline and 77 % at the eight-month time point . The odds of being anaemic were four to five times higher in children infected with malaria compared to those without malaria . Ascaris infection alone did not increase the odds of being anaemic , indicating that malaria was the main cause of anaemia in this population . There was no significant difference in the severity of anaemia between children singly infected with malaria and co-infected with malaria and Ascaris . Conclusion In this cohort of Nigerian preschool children , malaria infection was the major contributor to anaemia status . Ascaris co-infection neither exacerbated nor ameliorated the severity of malarial anaemia BACKGROUND Antimalarial drug resistance is now well established in both Plasmodium falciparum and Plasmodium vivax . In southern Papua , Indonesia , where both strains of plasmodia coexist , we have been conducting a series of studies to optimize treatment strategies . METHODS We conducted a r and omized trial that compared the efficacy and safety of dihydroartemisinin-piperaquine ( DHP ) with artesunate-amodiaquine ( AAQ ) . The primary end point was the overall cumulative parasitological failure rate at day 42 . RESULTS Of the 334 patients in the evaluable patient population , 185 were infected with P. falciparum , 80 were infected with P. vivax , and 69 were infected with both species . The overall parasitological failure rate at day 42 was 45 % ( 95 % confidence interval [ CI ] , 36%-53 % ) for AAQ and 13 % ( 95 % CI , 7.2%-19 % ) for DHP ( hazard ratio [ HR ] , 4.3 ; 95 % CI , 2.5 - 7.2 ; P<.001 ) . Rates of both recrudescence of P. falciparum infection and recurrence of P. vivax infection were significantly higher after receipt of AAQ than after receipt of DHP ( HR , 3.4 [ 95 % CI , 1.2 - 9.4 ] and 4.3 [ 95 % CI , 2.2 - 8.2 ] , respectively ; P<.001 ) . By the end of the study , AAQ recipients were 2.95-fold ( 95 % CI , 1.2- to 4.9-fold ) more likely to be anemic and 14.5-fold ( 95 % CI , 3.4- to 61-fold ) more likely to have carried P. vivax gametocytes . CONCLUSIONS DHP was more effective and better tolerated than AAQ against multidrug-resistant P. falciparum and P. vivax infections . The prolonged therapeutic effect of piperaquine delayed the time to P. falciparum reinfection , decreased the rate of recurrence of P. vivax infection , and reduced the risk of P. vivax gametocyte carriage and anemia Background Many countries have implemented artemisinin-based combination therapy ( ACT ) for the first-line treatment of malaria . Although many studies have been performed on efficacy and tolerability of the combination arthemeter-lumefantrine ( AL ) or dihydroartemisinin-piperaquine ( DP ) , less is known of the effect of these drugs on gametocyte development , which is an important issue in malaria control . Methods and results In this two-arm r and omized controlled trial , 146 children were treated with either AL or DP . Both groups received directly observed therapy and were followed for 28 days after treatment . Blood sample s were analysed with microscopy and NASBA . In comparison with microscopy NASBA detected much more gametocyte positive individuals . Moreover , NASBA showed a significant difference in gametocyte clearance in favour of AL compared to DP . The decline of parasitaemia was slower and persistence or development of gametocytes was significantly higher and longer at day 3 , 7 and 14 in the DP group but after 28 days no difference could be observed between both treatment arms . Conclusion Although practical considerations could favour the use of one drug over another , the effect on gametocytogenesis should also be taken into account and studied further using molecular tools like NASBA . This also applies when a new drug is introduced . Trial registration Current controlled trials IS RCT Background Artemisinin combination therapy has become the st and ard of care for uncomplicated malaria in most of Africa . However , there is limited data on the safety and tolerability of these drugs , especially in young children and patients co-infected with HIV . Methods A longitudinal , r and omized controlled trial was conducted in a cohort of HIV-infected and uninfected children aged 4 - 22 months in Tororo , Ug and a. Participants were r and omized to treatment with artemether-lumefantrine ( AL ) or dihydroartemisinin-piperaquine ( DP ) upon diagnosis of their first episode of uncomplicated malaria and received the same regimen for all subsequent episodes . Participants were actively monitored for adverse events for 28 days and then passively for up to 63 days after treatment . This study was registered in Clinical Trials.gov ( registration # NCT00527800 ) . Results A total of 122 children were r and omized to AL and 124 to DP , result ing in 412 and 425 treatments , respectively . Most adverse events were rare , with only cough , diarrhoea , vomiting , and anaemia occurring in more than 1 % of treatments . There were no differences in the risk of these events between treatment groups . Younger age was associated with an increased risk of diarrhoea in both the AL and DP treatment arms . Retreatment for malaria within 17 - 28 days was associated with an increased risk of vomiting in the DP treatment arm ( HR = 6.47 , 95 % CI 2.31 - 18.1 , p < 0.001 ) . There was no increase in the risk of diarrhoea or vomiting for children who were HIV-infected or on concomitant therapy with antiretrovirals or trimethoprim-sulphamethoxazole prophylaxis . Conclusion Both AL and DP were safe and well tolerated for the treatment of uncomplicated malaria in young HIV-infected and uninfected children . Trial Registration Clinical Trials.gov : NCT00527800 ; http:// clinical Background The emergence of artemisinin-resistant P. falciparum malaria in South-East Asia highlights the need for continued global surveillance of the efficacy of artemisinin-based combination therapies . Methods On the Kenyan coast we studied the treatment responses in 474 children 6–59 months old with uncomplicated P. falciparum malaria in a r and omized controlled trial of dihydroartemisinin-piperaquine vs. artemether-lumefantrine from 2005 to 2008 . ( IS RCT N88705995 ) Results The proportion of patients with residual parasitemia on day 1 rose from 55 % in 2005–2006 to 87 % in 2007–2008 ( odds ratio , 5.4 , 95%CI , 2.7–11.1 ; P<0.001 ) and from 81 % to 95 % ( OR , 4.1 , 95%CI , 1.7–9.9 ; P = 0.002 ) in the DHA-PPQ and AM-LM groups , respectively . In parallel , Kaplan-Meier estimated risks of apparent recrudescent infection by day 84 increased from 7 % to 14 % ( P = 0.1 ) and from 6 % to 15 % ( P = 0.05 ) with DHA-PPQ and AM-LM , respectively . Coinciding with decreasing transmission in the study area , clinical tolerance to parasitemia ( defined as absence of fever ) declined between 2005–2006 and 2007–2008 ( OR body temperature > 37.5 ° C , 2.8 , 1.9–4.1 ; P<0.001 ) . Neither in vitro sensitivity of parasites to DHA nor levels of antibodies against parasite extract accounted for parasite clearance rates or changes thereof . Conclusions The significant , albeit small , decline through time of parasitological response rates to treatment with ACTs may be due to the emergence of parasites with reduced drug sensitivity , to the coincident reduction in population -level clinical immunity , or both . Maintaining the efficacy of artemisinin-based therapy in Africa would benefit from a better underst and ing of the mechanisms underlying reduced parasite clearance rates . Trial Registration Controlled-Trials.com IS RCT Background The choice of appropriate artemisinin-based combination therapy depends on several factors ( cost , efficacy , safety , reinfection rate and simplicity of administration ) . To assess whether the combination dihydroartemisinin-piperaquine ( DP ) could be an alternative to artemether-lumefantrine ( AL ) , the efficacy and the tolerability of the two products for the treatment of uncomplicated falciparum malaria in sub-Saharan Africa have been compared . Methods A multicentric open r and omized controlled clinical trial of three-day treatment of DP against AL for the treatment of two parallel groups of patients aged two years and above and suffering from uncomplicated falciparum malaria was carried out in Cameroon , Côte d'Ivoire and Senegal . Within each group , patients were r and omly assigned supervised treatment . DP was given once a day for three days and AL twice a day for three days . Follow-up visits were performed on day 1 to 4 and on day 7 , 14 , 21 , 28 to evaluate clinical and parasitological results . The primary endpoint was the recovery rate by day 28 . Results Of 384 patients enrolled , 197 were assigned DP and 187 AL . The recovery rates adjusted by genotyping , 99.5 % in the DP group and 98.9 % in the AL group , were not statistically different ( p = 0.538 ) . No Early Therapeutic Failure ( ETF Output:	The frequency of other adverse events is probably similar with both combinations ( moderate quality evidence ) . DHA‐P is associated with less nausea , vomiting , dizziness , sleeplessness , and palpitations compared to artesunate plus mefloquine ( moderate quality evidence ) . DHA‐P was associated with more frequent prolongation of the QTc interval ( low quality evidence ) , but no cardiac arrhythmias were reported . In Asia , dihydroartemisinin‐piperaquine is as effective as artesunate plus mefloquine , and is better tolerated
MS21288	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVES --To establish , in a double blind manner , the antiparkinsonian effects of repeated dosing with entacapone , a peripheral COMT inhibitor . METHODS --A one month , cross over study was conducted . During the two four-week treatment periods , entacapone ( 200 mg ) or placebo was given with each levodopa dose four to 10 times daily . Motor responses were repeatedly quantified using the motor part of UPDRS . Plasma levodopa and its metabolites were measured . RESULTS --Entacapone prolonged the availability of levodopa in the plasma and thus to the brain by decreasing its peripheral O-methylation and slowing its elimination rate , without affecting the maximum plasma levodopa concentration or the time to maximum concentration . Corresponding with the pharmacokinetic findings , entacapone prolonged the duration of motor response to an individual levodopa/DDC inhibitor dose by 34 minutes ( 24 % , P = 0.001 ) and dyskinesiae by 39 minutes ( 37 % , P = 0.002 ) compared with placebo , without affecting their magnitude or starting time . Entacapone treatment result ed in a reduction of 16 % in the mean total daily levodopa dose due to dyskinesiae . Also , according to the home diaries , the mean daily " on " time increased by 2.1 hours compared with placebo , despite the lowered mean levodopa intake . CONCLUSION --The efficacy of repeated entacapone dosing as an adjuvant to levodopa/DDC inhibitor treatment for Parkinson 's disease with levodopa related fluctuations is verified Motor fluctuations associated with levodopa therapy are common problems encountered in the long‐term treatment of Parkinson 's disease ( PD ) . Entacapone , a peripherally acting , reversible inhibitor of catechol‐O‐methyltransferase , slows the elimination of levodopa in humans by reducing the formation of 3‐O‐methyldopa . We conducted a placebo‐controlled , double‐blind , parallel‐group , multicenter trial of entacapone in PD patients with motor fluctuations . Two hundred five patients were r and omized to receive either entacapone 200 mg or matching placebo with each dose of levodopa and were followed for 24 weeks . The primary measure of efficacy was the change in percentage of “ on ” time ( relief of parkinsonism ) while awake , as recorded by subjects at home in diaries completed at 30‐minute intervals . At baseline , patients averaged approximately 10 hours of “ on ” time per day while awake ( 60.5 % “ on ” time ) , and entacapone treatment increased the percent “ on ” time by 5.0 percentage points . The effect of entacapone was more prominent in patients with a smaller percent “ on ” time ( < 55 % ) at baseline , and increased as the day wore on . Entacapone is effective at increasing the duration of response to levodopa and at relieving parkinsonism in patients experiencing motor flucturations and was well tolerated during the 24 weeks of treatment OBJECTIVE The objective of this study was to examine the cost-effectiveness of a complementary treatment with entacapone versus usual care only in patients with Parkinson 's disease . METHODS The setting for this study was the Netherl and s. A Markov process model was constructed to model the average quality -adjusted life years ( QALYs ) and the costs of both treatments . The model examined a period of 5 years in order to capture the influence of symptom improvement and disease progression . Data for the construction of the model were derived from published literature , including large , multicenter , r and omized clinical trials in patients with end-of-dose motor fluctuations . Costs were obtained from published sources . RESULTS The results of the baseline analysis showed that the use of entacapone as complementary therapy in Parkinson 's disease slightly decreased the total average discounted costs from NLG 111,317 to NLG 110,038 , while effectiveness increased from 2.42 to 2.56 QALYs ( a 6 % increase ) . In addition , entacapone substantially increased time without severe fluctuations by 0.63 years . Sensitivity analyses confirmed the robustness of these findings . CONCLUSION The study shows that entacapone is a cost-effective treatment in patients with Parkinson 's disease : entacapone yields higher effectiveness in terms of both effectiveness measures ( time without severe fluctuations and QALYs ) , while costs remain quite similar to those for usual care . The additional drug costs for entacapone are offset by reductions in other costs Summary . Objectives : To evaluate the tolerability , safety and efficacy of Stalevo ® ( carbidopa , levodopa and entacapone ) in Parkinson ’s disease ( PD ) . Background : Levodopa provides the most effective symptom control for the treatment of Parkinson ’s disease ( PD ) . However , its long-term use is limited by the development of motor complications such as wearing-off . Catechol-O-methyltransferase ( COMT ) inhibitors such as entacapone extend the plasma half-life of levodopa and reduce ‘ off ’ time . Stalevo is a new levodopa product that combines carbidopa , levodopa and entacapone in one tablet . Clinical studies have not been reported with this compound . Design methods : An open-label , multi-center US trial evaluated 169 consecutive PD patients experiencing end-of-dose wearing-off , with ( n = 39 ) and without ( n = 130 ) mild dyskinesia . Patients were switched from immediate-release carbidopa/levodopa to Stalevo and were treated for four weeks . Assessment s included tolerability measures , adverse events profile , the disease-specific quality of life instrument PDQ-39 , UPDRS parts II , III , and question 39 and investigator and patient global clinical assessment s. Results : 14 subjects ( 8 % ) discontinued treatment with Stalevo , of which 12 ( 7 % ) were due to adverse events . 11/130 ( 8.5 % ) subjects developed new onset dyskinesia and 17/39 ( 43.6 % ) of patients with existing dyskinesia reported a worsening in their dyskinesia . However , this was managed by a change in dose in 21.4 % of patients and in another 10.7 % dyskinesias resolved without any need for dose adjustment . Other side effects were infrequent and mild , the most common being nausea ( 12.4 % ) dizziness ( 6.5 % ) and somnolence ( 6.5 % ) . Stalevo treatment result ed in significant improvements in PDQ-39 and UPDRS ( II + III ) scores ( p < 0.001 ) . Assessment of ‘ off ’ time demonstrated a reduction in off time in 32 % of patients , compared with an increase in 7 % of patients . Improvements were noted by both investigator ( 68.1 % ) and patient ( 68.6 % ) assessment s. Conclusions : Switching PD patients experiencing wearing-off from carbidopa/levodopa therapy to Stalevo was safe , well tolerated and result ed in clinical improvement Summary . The efficacy and tolerability of entacapone was investigated in a r and omized , double-blind , placebo-controlled , 3-month study of 162 patients with Parkinson 's disease ( PD ) treated with levodopa and a dopamine agonist and experiencing wearing-off motor fluctuations . Patients were r and omized in a 3 : 2 ratio to entacapone 200 mg or placebo , administered with each dose of levodopa . Efficacy was judged on the improvement of “ on ” and “ off ” time while awake ( Patient Diary and UPDRS part IV Item 39 ) , Investigators ' Global Assessment , the SF-36 Health Survey , and changes in levodopa dosages . Patients were monitored for adverse events , laboratory safety and vital signs throughout the study . Improvements in “ on ” time as assessed using patient diary data showed a trend in favour of entacapone , however these did not reach statistical significance . “ Off ” time while awake ( UPDRS part IV Item 39 ) showed an improvement of at least one category in 36 % of entacapone-treated patients , compared with 22 % in the control group ( p = 0.0038 ) . The proportion of patients showing an improvement at the Investigators ' Global Assessment was significantly higher ( p = 0.0006 ) in the entacapone-treated group of patients . Also , the proportion of patients with a reduction in their daily levodopa dose was significantly higher ( p = 0.02 ) in the entacapone group ( 28 % ) compared with placebo ( 13 % ) . As expected , the most frequent adverse events were dopamine-mediated ( dyskinesia : entacapone 31 % versus placebo 13 % ) , and harmless urinary discoloration . The modest increase in dyskinesias could be readily managed by levodopa down-adjustment , and , at study end there was no significant difference for the UPDRS “ overall dyskinesia score ” between entacapone and placebo . In conclusion , although the primary efficacy variable did not reach statistical significance , the present results demonstrate that entacapone provides additional antiparkinsonian benefits to levodopa therapy and is well tolerated in levodopa-treated PD patients experiencing wearing-off motor fluctuations despite adjunct dopamine agonist therapy Entacapone is a catechol-O-methyltransferase ( COMT ) inhibitor used as an adjunct to levodopa/dopa decarboxylase inhibitors in the treatment of Parkinson 's disease . Entacapone increases the bioavailability and reduces the daily variation of plasma levodopa when administered with st and ard levodopa preparations . These parameters were studied when entacapone was administered with a controlled-release levodopa preparation after repeated administrations throughout the day in 16 healthy male volunteers . On 2 test days , 200 mg entacapone or placebo was administered 4 times during the day at 4-hour intervals concomitantly with a single dose of controlled-release levodopa/carbidopa 100 mg/25 mg ( Sinemet CR ) . Plasma levodopa , 3-O-methyldopa ( 3-OMD ) , and carbidopa concentrations were measured before intake of the medication and then every 30 minutes for 16 hours ( until midnight ) , and less frequently up to 24 hours after the first levodopa dose . The minimum , maximum , and average concentration of levodopa ; the daily variation of levodopa concentration ; and the area under the time concentration curve ( AUC ) were calculated . The mean ( ±SD ) plasma levodopa AUC was 39 % ( P = 0.0001 ) higher with entacapone ( 11,802 ± 1454 ng/hour/mL ) compared with placebo ( 8465 ± 927 ng/hour/mL ) . The daily variation of plasma levodopa was reduced by about 25 % with entacapone ( P < 0.01 ) . Entacapone significantly reduced plasma 3-OMD concentration by about 50 % ( P = 0.0001 ) , indicating marked COMT inhibiting activity . There were no differences in plasma carbidopa concentrations . Entacapone significantly increased the bioavailability of levodopa and reduced its daily variation when administered concomitantly with a controlled-release levodopa preparation Objectives – To determine the efficacy and safety of the catechol‐O‐methyltransferase ( COMT ) inhibitor entacapone , used as an adjunct to levodopa , in Parkinson 's disease ( PD ) patients . Patients and methods – In this parallel group , r and omized , double‐blind study , 301 PD patients , the majority with motor fluctuations , received entacapone ( 200 mg ) or placebo with each daily dose of st and ard or controlled‐release ( CR ) levodopa . The 24‐week treatment period was followed by 2 weeks of entacapone withdrawal . Efficacy was determined by home diaries ( ` on ' and ` off ' times ) , Unified Parkinson 's Disease Rating Scale ( UPDRS ) and changes in levodopa dosage , and safety by adverse‐event inquiry , vital signs , electro cardiography ( ECG ) and laboratory tests . Results – In the total population , the UPDRS activities of daily living and motor scores were significantly improved ( P < 0.05 ) by entacapone vs placebo . In fluctuating patients , ` on ' time increased ( 1.7 h ) and ` off ' time decreased ( 1.5 h ) significantly more with entacapone than with placebo ( 0.5 and 0.6 h , respectively ; P < 0.05 ) , and the daily levodopa dose was reduced by 54 mg with entacapone and increased by 27 mg with placebo ( P < 0.05 ) . Entacapone benefit was lost on withdrawal . Entacapone efficacy was comparable between patients using CR and st and ard levodopa preparations . Increased dyskinesias ( entacapone 34 % , placebo 26 % ) and nausea ( 10 and 5 % , respectively ) , mostly occurring shortly after treatment initiation , were generally managed by reducing the levodopa dose . Diarrhoea ( entacapone 8 % , placebo 4 % ) was seldom severe . There were no differences in vital signs , ECG or laboratory results . Conclusion – Entacapone is an effective and safe levod Output:	Conclusions : This meta- analysis suggests that the entacapone used as adjuvant therapy to LD is effective in the management of later PD with fluctuation . However , patients on entacapone had a higher frequency of adverse events than those on placebo but no occurrence of severe adverse reactions
MS21289	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To evaluate the effects of intravenous morphine on pain reduction , physical examination , and diagnostic accuracy in children with acute abdominal pain . METHODS A r and omized , double-blind , placebo-controlled clinical trial was conducted at an emergency department of a tertiary care children 's hospital . Children aged 5 - 18 years with abdominal pain of < or = 5 days ' duration , pain score > or = 5 on a 0 - 10 visual analog scale , and need for surgical evaluation were eligible . Following the initial assessment , patients were r and omized to receive either 0.1 mg/kg morphine or an equal volume of saline . The pediatric emergency medicine physician and surgical consultant independently recorded the areas of tenderness to palpation and percussion , and their diagnoses before the study medication and 15 to 30 minutes later . RESULTS Sixty patients were enrolled , and 29 received morphine and 31 received saline . The demographic characteristics between the two groups were similar . The median reduction of pain score between the two study groups was 2 ( 95 % CI = 1 to 4 ; p = 0.002 ) . There was no significant change in the areas of tenderness in both study groups . Children with surgical conditions had persistent tenderness to palpation and /or percussion . There was no significant change in the diagnostic accuracy between the study groups and between the physician groups . All patients requiring laparotomy were identified and no significant complication was noted in the morphine group . CONCLUSIONS Intravenous morphine provides significant pain reduction to children with acute abdominal pain without adversely affecting the examination , and morphine does not affect the ability to identify children with surgical conditions 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 OBJECTIVES The total white blood cell ( WBC ) count and temperature are often expected to be elevated in patients with appendicitis . Clinicians often use the results of these parameters in making a judgment about the presence or absence of disease . The objective of this study was to assess the discriminatory value of the total WBC count and presenting body temperature in patients presenting to the emergency department ( ED ) with signs and symptoms suggestive of appendicitis . METHODS This was a prospect i ve consecutive case series in a university ED with an annual census of 38,000 . All patients presenting to the ED in whom the diagnosis of appendicitis was the attending physician 's primary consideration were enrolled . Measures included age , gender , symptoms , physical findings , patient temperature as taken in the ED , initial total WBC count , and discharge diagnosis . Admitted patients were followed up until surgical or clinical outcomes , and discharged patients were followed up by telephone two weeks after the initial visit . All statistical analysis was performed using StatsDirect version 1.9.8 . RESULTS A total of 293 patients were enrolled over a two-year study period . The total WBC count was measured in 274 cases , and the temperature was measured in 293 cases . There were 130 male patients and 163 female patients . The mean age of the patients was 30.8 years ( range , 7 - 75 years ) . Appendicitis was confirmed in 92 patients . In this study group of patients , a total WBC count > 10,000 cells/mm(3 ) had a sensitivity of 76 % ( 95 % confidence interval [ 95 % CI ] = 65 % to 84 % ) and a specificity of 52 % ( 95 % CI = 45 % to 60 % ) . The positive predictive value ( PPV ) was 42 % ( 95 % CI = 35 % to 51 % ) , and the negative predictive value ( NPV ) was 82 % ( 95 % CI = 74 % to 89 % ) . The positive likelihood ratio ( LR ) was 1.59 ( 95 % CI = 1.31 to 1.93 ) , and the negative LR was 0.46 ( 95 % CI = 0.31 to 0.67 ) . A temperature > 99.0 degrees F had a sensitivity of 47 % ( 95 % CI = 36 % to 57 % ) and a specificity of 64 % ( 95 % CI = 57 % to 71 % ) . The PPV was 37 % ( 95 % CI = 29 % to 46 % ) , and the NPV was 72 % ( 95 % CI = 65 % to 79 % ) . The positive LR was 1.3 ( 95 % CI = 0.97 to 1.72 ) , and the negative LR was 0.82 ( 95 % CI = 0.65 to 1.01 ) . The areas under the curve for the receiver-operating characteristic ( ROC ) curve were 0.72 ( 95 % CI = 0.65 to 0.79 ) and 0.59 ( 95 % CI = 0.52 to 0.66 ) for an elevated total WBC count and an elevated temperature , respectively . CONCLUSIONS An elevated total WBC count > 10,000 cells/mm(3 ) , while statistically associated with the presence of appendicitis , had very poor sensitivity and specificity and almost no clinical utility . There was minimal statistical association between a temperature of > 99 degrees F and the presence of appendicitis . The ROC curve suggests there is no value of total WBC count or temperature that has sufficient sensitivity and specificity to be of clinical value in the diagnosis of appendicitis . Clinicians should be wary of reliance on either elevated temperature or total WBC count as an indicator of the presence of appendicitis HYPOTHESIS Ultrasonography can be efficiently performed using new criteria for the diagnosis of acute appendicitis . DESIGN Prospect i ve trial . PATIENTS Eighty-nine patients admitted to the hospital with suspected appendicitis between March 1998 and November 2000 . INTERVENTION At hospital admission , a staff surgeon evaluated each patient and determined whether the patient had appendicitis requiring immediate surgery or another disease . Patients then underwent ultrasonography . A sonographic transducer was placed on the area of maximal tenderness . When the pathological manifestation was depicted , the examiner slipped a fingertip between the transducer and the patient 's skin and then pressed the area of depicted pathological manifestation to find pinpoint tenderness . When maximal pinpoint tenderness was noted on the appendix or on pathological manifestations contiguous to the appendix , we diagnosed the condition as appendicitis . MAIN OUTCOME MEASURES Sensitivity , specificity , positive and negative predictive values , and overall accuracy . RESULTS The diagnosis of appendicitis by this criteria had a sensitivity of 86.7 % , a specificity of 89.7 % , a positive predictive value of 94.5 % , a negative predictive value of 76.5 % , and overall accuracy of 87.6 % . All 50 patients with pinpoint tenderness noted on the appendix had appendicitis . The surgeon 's initial clinical impression had a sensitivity of 83.3 % , a specificity of 44.8 % , a positive predictive value of 75.8 % , a negative predictive value of 56.5 % , and overall accuracy of 70.8 % . CONCLUSIONS The efficacy of ultrasonography using the simple criteria was superior to that of the surgeon 's initial clinical impression ( P<.001 ) . Our ultrasonographic criteria for the diagnosis of appendicitis are simple to use and efficient The objective of this study was to examine current practice patterns of analgesia administration among emergency physicians ( EPs ) when caring for a patient with an acute abdomen . Cross sectional data were acquired by a survey mailed in October 1997 to 1,000 American College of Emergency Physicians ( ACEP ) members from a purchased ACEP mailing list which contained 1,000 r and omized ACEP members . A repeat survey was sent to nonresponders 2 months later and a r and om subset of recurrent nonresponders were telephoned . The question naire focused on physician demographics , practice patterns , and factors which influenced physician decision of when and whether to administer pain medication , specifically opiates , to patients with an acute abdomen . Forty-four percent of surveys were returned . Seventy-seven percent of respondents were men with an average of 10 years of experience . Fifty-seven percent were residency trained in emergency medicine . Although eighty-five percent felt that the conservative administration of pain medication did not change important physical findings on the physical examination , 76 % choose not to give an opiate analgesic until after the examination by a surgeon . Twenty-five percent of patients did not receive any pain medication in the department . In conclusion , although EPs report that the judicious administration of pain medication does not mask important examination findings , the majority wait until after the surgeon has evaluated the patient to deliver analgesics Abstract Objectives : To evaluate the impact of early abdominopelvic computed tomography in patients with acute abdominal pain of unknown cause on length of hospital stay and accuracy of diagnosis . Design : R and omised , prospect i ve controlled trial . Setting : Teaching hospital in Engl and . Participants : 120 patients admitted with acute abdominal pain for which no immediate surgical intervention or computed tomography was indicated . Intervention : 55 participants were prospect ively r and omised to early computed tomography ( within 24 hours of admission ) and 65 to st and ard practice ( radiological investigations as indicated ) . Main outcome measures : Length of hospital stay , accuracy of diagnosis , and , owing to a possible effect on inpatient mortality , deaths during the study . Results : Early computed tomography reduced the length of hospital stay by 1.1 days ( geometric mean 5.3 days ( range 1 to 31 ) v 6.4 days ( 1 to 60 ) ) , but the difference was non-significant ( 95 % confidence interval , 8 % shorter stay to 56 % longer stay , P=0.17 ) . Early computed tomography missed significantly fewer serious diagnoses . Seven in patients in the st and ard practice arm died . Only 50 % ( 59 of 118 ) of diagnoses on admission were correct at follow up at 6 months , but this improved to 76 % ( 90 ) of diagnoses after 24 hours . Conclusions : Early abdominopelvic computed tomography for acute abdominal pain may reduce mortality and length of hospital stay . It can also identify unforeseen conditions and potentially serious complications . What is already known on this topic Computed tomography improves the accuracy of diagnosis of several acute abdominal conditions Uncontrolled studies have shown improvements in accuracy of diagnosis after computed tomography ; none have described an effect on mortality What this study adds Early abdominopelvic computed tomography for acute abdominal pain can identify unforeseen serious abdominal conditions It may also reduce length of hospital stay and might reduce inpatient BACKGROUND The accuracy of the clinical diagnosis of acute appendicitis in patients more than 50 years old was studied in connection with the Research Committee of the World Organization of Gastroenterology ( OMGE ) survey of acute abdominal pain . Criteria for inclusion and the diagnostic criteria in this prospect i ve study were those set out by the OMGE Research Committee . METHODS The clinical findings in each patient were recorded in detail , using a predefined structured data collection sheet , and the collected data were compared with the final diagnosis of the patients . Twenty-three preoperative clinical history variables , 14 clinical signs , and 3 tests were evaluated in a single variable and multivariate analysis . RESULTS In multivariate logistic regression analysis the most significant predictors of acute appendicitis in patients more than 50 years old were tenderness ( relative risk ( RR ) = 39.4 ) , rigidity ( RR = 18.8 ) , and pain at diagnosis ( RR = 11.0 ) . The sensitivity of the preoperative clinical decision is detecting acute appendicitis in the aged was 0.87 , with a specificity of 0.92 , an efficiency of 0.91 and a usefulness index ( UI ) of 0.69 . The computer-aided diagnostic score ( DS ) reached a sensitivity of 0.92 in detecting acute appendicitis , with a specificity of 0.90 and an efficiency of 0.90 . When the patients with a DS value between - Output:	Improvement with use of opioid analgesia was verified in variables patient comfort , reduction of pain , changes in physical examination . AUTHORS ' CONCLUSIONS The review provide some evidence to support the notion that the use of opioid analgesics in patients with acute abdominal pain is helpful in terms of patient comfort and does not retard decisions to treat
MS21290	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Tobacco use is the single most important preventable cause of death in military personnel . The purpose of this r and omized clinical trial was to evaluate the effectiveness of two behavioral interventions when added to nicotine-replacement therapy on smoking cessation . The sample of 512 included 52 % active duty military , 29 % family , 11 % retirees , and 8 % Department of Defense civilians . There was a main effect of compliance at the end of the program ( EOP ) ; 69 % of those who attended 75 % of the classes were abstinent from tobacco ; regression analysis found the more intensive program to be twice as effective at EOP and at 3 months , an outcome not continued at 6 months . The longer , more intensive V and erbilt University Medical Center program was significantly more effective at helping the civilian portion of the population ( 85 % versus 60 % in the American Cancer Society program ) but not the active duty participants Subjects ( N = 139 ) were assigned to intensive behavioral or to low-contact smoking treatment and to 2-mg nicotine gum or to placebo gum in a 2 X 2 factorial design . The 2-mg gum produced higher abstinence rates than did the placebo . Subjects receiving the low-contact condition plus the 2-mg nicotine gum had excellent abstinence rates at both 26 weeks ( 56 % abstainers ) and 52 weeks ( 50 % abstainers ) . Smokers who scored at the median on a measure of physical dependence to nicotine were more likely to benefit by nicotine gum treatment than subjects who scored either higher or lower , but this relation was nonsignificant . The results of this study are compared with an earlier nonblind trial Sustained-release bupropion and nortriptyline have been shown to be effcacious in treating cigarette smoking . Psychological intervention is also recognized as efficacious . The cost and cost-effectiveness of the 2 drug therapies have not been estimated . It was hypothesized that nortriptyline would be more cost-effective than bupropion . Hypotheses were not originally proposed concerning the cost-effectiveness of psychological versus drug treatment , but the 2 were compared using exploratory analyses . This was a 3 ( bupropion versus nortriptyline versus placebo ) by 2 ( medical management alone versus medical management plus psychological intervention ) r and omized trial . Participants were 220 cigarette smokers . Outcome measures were cost and cost-effectiveness computed at week 52 . Nortriptyline cost less than bupropion . Nortriptyline was more cost-effective than bupropion ; the difference was not statistically significant . Psychological intervention cost less than the 2 drug treatments , and was more cost-effective , but not significantly so . Prospect i ve investigations of the cost and cost-effectiveness of psychological and pharmacological intervention , using adequate sample sizes , are warranted Objective - To compare the effectiveness of two different stop smoking interventions . Design - A r and omised , controlled trial . Results based on intention to treat . Setting - Three towns in the south-eastern part of Norway . Interventions - Visits to GP for " practice as usual " ( GP group ) or participation in the behavioural programme SmokEnders ( SE group ) with follow-up 2 weeks , 2 months and 1 year after an agreed stopping date . Subjects - 139 smokers recruited through open invitation . Main outcome measure - Self-reported smoking stop rate 2 weeks , 2 months and 1 year after an agreed stopping date , completed with biochemical indicators by the 1-year registration . Results ? Two weeks after the agreed cessation date , 10/70 ( 14 % ) of the GP group and 46/69 ( 67 % ) of the SE group had stopped smoking . After 2 months , 9/70 ( 13 % ) in the GP group and 37/69 ( 54 % ) in the SE group were non-smokers . One year after cessation 5/70 ( 7 % ) in the GP group and 21/69 ( 30 % ) in the SE group were non-smokers . Conclusions ? Both interventions were effective as measured by the smoking cessation rate . However , the intervention in the SE group was considerably more effective than in the GP group , which suffered from a sizeable number of drop-outs BACKGROUND Sustained-release bupropion hydrochloride and nortriptyline hydrochloride have been shown to be efficacious in the treatment of cigarette smoking . It is not known whether psychological intervention increases the efficacy of these antidepressants . This study compared both drugs with placebo . It also examined the efficacy of these 2 drugs and placebo with and without psychological intervention . METHODS This was a 2 ( medical management vs psychological intervention ) x 3 ( bupropion vs nortriptyline vs placebo ) r and omized trial . Participants were 220 cigarette smokers . Outcome measures were biologically verified abstinence from cigarettes at weeks 12 , 24 , 36 , and 52 . RESULTS Psychological intervention produced higher 7-day point-prevalence rates of biochemically verified abstinence than did medical management alone . With the use of point-prevalence abstinence , both nortriptyline and bupropion were more efficacious than placebo . On rates of 1-year continuous abstinence , the 2 drugs did not differ from each other or from placebo . Psychological intervention did not differ from medical management alone on rates of 1-year continuous abstinence . CONCLUSIONS Both nortriptyline and bupropion are efficacious in producing abstinence in cigarette smokers . Similarly , psychological intervention produces better abstinence rates than simple medical management . Both drugs , and psychological intervention , have limited efficacy in producing sustained abstinence . The data also suggest that combined psychological intervention and antidepressant drug treatment may not be more effective than antidepressant drug treatment alone Following an initial smoking program , 33 subjects were r and omly assigned to one of four maintenance strategy conditions developed to investigate the Marlatt and Gordon cognitive-behavioral model of relapse . Two out of three components of the model were supported . Abstinent subjects given problem solving training did not show significant relapse while those given an attention placebo control did relapse significantly . Self-efficacy expectations predicted smoking rate up to 5-month follow-up . Contrary to expectations based on the Marlatt and Gordon model , subjects taught to cope with the guilt and sense of personal failure associated with a relapse episode showed considerable relapse The present investigation assessed the effectiveness of nicotine fading as a non-aversive alternative to oversmoking . Subjects ( 66 women and 64 men ) were r and omly assigned to oversmoking , nicotine fading , nicotine fading/smokeholding , and a nonmaintenance control . Results failed to indicate the expected superiority of nicotine fading/maintenance over the control condition . Instead , the addition of smokeholding appeared to produce a significant incremental effect over nicotine fading alone . Unfortunately , 12-month follow-up revealed considerable relapse across conditions and no significant treatment effects . Even so , absolute outcome for nicotine fading/smokeholding was encouraging . This procedure is both safe and apparently very acceptable to subjects . If the current results can be replicated , a clinical ly effective technique will have been established with applicability in both clinic and self-help setting This study is a r and omized , double-blind , placebo-controlled clinical trial examining the effects of an intensive cognitive-behavioral mood management treatment ( CBTD ) and of bupropion , both singularly and in combination , on smoking cessation in adult smokers . As an extension of our previous work , we planned to examine the synergistic effects of CBTD and bupropion on smoking cessation outcomes in general and among smokers with depression vulnerability factors . Participants were 524 smokers ( 47.5 % female , M ( age ) = 44.27 years ) who were r and omized to one of four 12-week treatments : ( a ) st and ard , cognitive-behavioral smoking cessation treatment ( ST ) plus bupropion ( BUP ) , ( b ) ST plus placebo ( PLAC ) , ( c ) st and ard cessation treatment combined with cognitive-behavioral treatment for depression ( CBTD ) plus BUP , and ( d ) CBTD plus PLAC . Follow-up assessment s were conducted 2 , 6 , and 12 months after treatment , and self-reported abstinence was verified biochemically . Consistent with previous studies , bupropion , in comparison with placebo , result ed in better smoking outcomes in both intensive group treatments . Adding CBTD to st and ard intensive group treatment did not result in improved smoking cessation outcomes . In addition , neither CBTD nor bupropion , either alone or in combination , was differentially effective for smokers with single-past-episode major depressive disorder ( MDD ) , recurrent MDD , or elevated depressive symptoms . However , findings with regard to recurrent MDD and elevated depressive symptoms should be interpreted with caution given the low rate of recurrent MDD and the low level of depressive symptoms in our sample . An a priori test of treatment effects in smokers with these depression vulnerability factors is warranted in future clinical trials This article describes the test of the hypothesis that a cognitive-behavioral mood management intervention would be effective for smokers with a history of major depressive disorder ( MDD ) . The method was r and omized trial ; the assessment s occurred at Weeks 0 , 8 , 12 , 26 , and 52 . Ss were 149 smokers ; 31 % had a history of MDD . All received 2 mg of nicotine gum . Mood management was provided in 10 group sessions over 8 weeks . St and ard treatment was provided in 5 group sessions over 8 weeks . Outcome was continuous abstinence . History-positive Ss were more likely to be abstinent when treated with mood management . Treatment condition differences were not significant for history-negative Ss . For history-positive Ss , less anger at baseline predicted abstinence . For history-negative Ss , more years smoked and higher baseline carbon monoxide ( CO ) predicted abstinence . Cognitive-behavioral therapy did not affect mood after quitting . Abstinence predictors differed as a function of baseline diagnosis Abstract The role of aversive conditioning in rapid smoking was examined by r and omly assigning smokers to one of three aversive treatments design ed to induce three distinct levels of central malaise . These treatments , full-scale rapid smoking ( FS ; n = 22 ) , truncated rapid smoking ( TC : n = 20 ) and rapid puffing ( RP ; n = 20 ) were combined with a full-scale counseling package . A fourth treatment , full-scale rapid smoking with reduced counseling ( RC ; n = 20 ) , was included to evaluate the contribution of coping response training to rapid-smoking efficacy . Among post-treatment measures of aversion , only heart rate ( HR ) response to cigarettes discriminated groups , with FS Ss exhibiting an apparent conditioned cardiac acceleration to cigarettes . Six-month follow-up data revealed that both the type of counseling and level of aversion had an impact on cigarette abstinence . At 6-months post-treatment , the FS group produced the best outcome , while the TC group and the RC group had the worst outcomes . The RP group was intermediate to these groups . Regression analysis showed that across all groups , confidence ratings of remaining abstinent were most predictive of outcome whereas within the two full-scale rapid-smoking treatments , post-treatment HR response to cigarettes was most predictive of latency to relapse . The results were discussed with respect to the contributions of aversion conditioning and full counseling to the success of aversive treatment packages for smoking cessation BACKGROUND New training programs need to be developed to help Chinese smokers achieve quitting . The objective of this study was to assess the effectiveness of a group smoking cessation intervention based on social cognitive theory among Chinese smokers . METHOD A total of 225 smokers were eligible for the study and were r and omly assigned to an intervention group ( n=118 ) and a control group ( n=107 ) . The intervention group received the course soon after a baseline survey , whereas the control group received routine training in the first 6 months , and then took the same course . Effectiveness was evaluated at 6-month and 1-year follow-up from baseline . RESULTS After 6 months , 40.5 % ( 47/116 ) in the intervention group and 5.0 % ( 5/101 ) in the control group quit smoking ( absolute risk reduction : 35.5 % [ 95 % confidence interval ( CI ) : 24.2 - 46.8 % ] ) . The 6-month continuous abstinence rate was 28.4 % ( 33/116 ) in the intervention group and 3.0 % ( 3/101 ) in the control group ( absolute risk reduction 25.4 % [ 95 % CI : 15.6 - 35.2 % ] ) . At 1-year follow-up , the proportion of quitting and the 6-month abstinence rate in the intervention group were 35.8 % and 22.0 % , respectively . The factors associated with smoking cessation during the 6 month period were intervention ( adjusted odds ratio [OR]=6.42 [ 95 % CI : 2.46 - 13.28 ] ) , as well as anticipation of quitting ( adjusted OR=1.46 [ 95 % CI : 1.12 - 1.91 ] ) and skill self-efficacy score in the baseline ( adjusted OR=1.04 [ 95 % CI : 1.01 - Output:	There was no evidence that group therapy was more effective than a similar intensity of individual counselling . There was variation in the extent to which those offered group therapy accepted the treatment . There was limited evidence that programmes which included components for increasing cognitive and behavioural skills and avoiding relapse were more effective than same length or shorter programmes without these components . We did not find an effect of manipulating the social interactions between participants in a group programme on outcome . AUTHORS ' CONCLUSIONS Group therapy is better for helping people stop smoking than self help , and other less intensive interventions . There is not enough evidence to evaluate whether groups are more effective , or cost-effective , than intensive individual counselling . There is not enough evidence to support the use of particular psychological components in a programme beyond the support and skills training normally included
MS21291	*TASK* the task is to summarize an input biomedical literature in six sentences *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 variety of patient and product-related factors influenced the outcome of 6379 transfusions given to 533 patients in the Trial to Reduce Alloimmunization to Platelets ( TRAP ) . Responses measured were platelet increments , interval between platelet transfusions , and platelet refractoriness . Patient factors that improved platelet responses were splenectomy and increasing patient age . In contrast , at least 2 prior pregnancies , male gender , splenomegaly , bleeding , fever , infection , disseminated intravascular coagulation , increasing height and weight , lymphocytotoxic antibody positivity , an increasing number of platelet transfusions , or receiving heparin or amphotericin were associated with decreased posttransfusion platelet responses . Platelet factors that were associated with improved platelet responses were giving ABO-compatible platelets , platelets stored for 48 hours or less , and giving large doses of platelets while ultraviolet B ( UV-B ) or gamma irradiation decreased platelet responses . However , in alloimmunized lymphocytoxic antibody-positive patients , the immediate increment to UV-B-irradiated platelets was well maintained , whereas all other products showed substantial reductions . Refractoriness to platelet transfusions developed in 27 % of the patients . Platelet refractoriness was associated with lymphocytotoxic antibody positivity , heparin administration , fever , bleeding , increasing number of platelet transfusions , increasing weight , at least 2 pregnancies , and male gender . The only factors that reduced platelet refractoriness rates were increasing the dose of platelets transfused or transfusing filtered apheresis platelets BACKGROUND The storage duration of platelet ( PLT ) units is limited to 5 to 7 days . This study investigates whether PLT storage duration is associated with patient outcomes in critically ill patients . STUDY DESIGN AND METHODS This study was a retrospective analysis of critically ill patients admitted to the intensive care unit ( ICU ) of two hospitals in Australia who received one or more PLT transfusions from 2008 to 2014 . Storage duration was approached in several different ways . Outcome variables were hospital mortality and ICU-acquired infection . Associations between PLT storage duration and outcomes were evaluated using multiple logistic regression and also by Cox regression . RESULTS Among 2250 patients who received one or more PLT transfusions while in the ICU , the storage duration of PLTs was available for 64 % of patients ( 1430 ) . In-hospital mortality was 22.1 % and ICU infection rate 7.2 % . When comparing patients who received PLTs of a maximum storage duration of not more than 3 , 4 , or 5 days , there were no significant differences in baseline characteristics . After confounders were adjusted for , the storage duration of PLTs was not independently associated with mortality ( 4 days vs. ≤3 days , odds ratio [ OR ] 0.88 , 95 % confidence interval [ CI ] 0.59 - 1.30 ; 5 days vs. ≤3 days , OR 0.97 , 95 % CI 0.68 - 1.37 ) or infection ( 4 days vs. ≤3 days , OR 0.71 , 95 % CI 0.39 - 1.29 ; 5 days vs. ≤3 days , OR 1.11 , 95 % CI 0.67 - 1.83 ) . Similar results were obtained regardless of how storage duration of PLTs was approached . CONCLUSIONS In this large observational study in a heterogeneous ICU population , storage duration of PLTs was not associated with an increased risk of mortality or infection Pathogen reduction ( PR ) of platelet products increases costs and available clinical studies are equivocal with respect to clinical and haemostatic effectiveness . We conducted a multicentre , open‐label , r and omized , non‐inferiority trial comparing the clinical effectiveness of buffy‐coat derived leucoreduced platelet concentrates ( PC ) stored for up to 7 d in plasma with platelets stored in platelet additive solution III ( PASIII ) without and with treatment with amotosalen‐HCl/ultraviolet‐A ( UVA ) photochemical pathogen reduction ( PR‐PASIII ) . Primary endpoint of the study was 1‐h corrected count increment ( CCI ) . Secondary endpoints were 24‐h CCI , bleeding , transfusion requirement of red cells and PC , platelet transfusion interval and adverse transfusion reactions . Compared to plasma‐PC , in the intention to treat analysis of 278 evaluable patients the mean difference for the 1‐h CCI of PR‐PASIII‐PC and PASIII‐PC was −31 % ( P < 0·0001 ) and −9 % ( P = n.s . ) , respectively . Twenty‐seven patients ( 32 % ) had bleeding events in the PR‐PASIII arm , as compared to 19 ( 19 % ) in the plasma arm and 14 ( 15 % ) in the PASIII arm ( P = 0·034 ) . Despite the potential advantages of pathogen ( and leucocyte ) inactivation of amotosalen‐HCl/UVA‐treated platelet products , their clinical efficacy is inferior to platelets stored in plasma , warranting a critical re appraisal of employing this technique for clinical use BACKGROUND Bacterial screening offers the possibility of extending platelet ( PLT ) storage to Day 7 . We conducted a noninferiority , crossover trial comparing PLTs stored for 6 or 7 days versus 2 to 5 days . STUDY DESIGN AND METHODS Stable hematology patients were allocated to receive blocks of 2- to 5- and 6- or 7-day PLTs in r and om order . The primary outcome was the proportion of successful transfusions during the first block , defined as a corrected count increment ( CCI ) of more than 4.5 at 8 to 24 hours posttransfusion . RESULTS Of 122 patients with an evaluable first block , 87 ( 71 % ) and 84 ( 69 % ) had successful transfusions after 2- to 5- and 6- or 7-day PLTs of mean ( SD ) ages of 3.8 ( 1.0 ) and 6.4 ( 0.5 ) days , respectively . Six- or 7-day PLTs were declared noninferior to 2- to 5-day PLTs since the upper confidence interval ( CI ) limit was less than the predefined noninferiority margin of 10 % ( 95 % CI , -14.0 % to 9.1 % ; p = 0.766 ) . Logistic regression analysis gave an adjusted odds ratio of 0.86 ( 95 % CI , 0.47 - 1.58 ; p = 0.625 ) . Mean ( SD ) 8- to 24-hour CCIs were 9.4 ( 7.9 ) and 7.7 ( 7.1 ) after transfusion with 2- to 5- or 6- or 7-day PLTs ( 95 % CI , -3.31 to 0.03 ; p = 0.054 ) . The proportions of days with bleeding scores of WHO Grade 2 or higher were 13 % ( 38/297 days ) and 11 % ( 32/296 days ; 95 % CI , -3.2 to 7.2 ; p = 0.454 ) . Median interval to next PLT transfusion ( 2 days ) was unaffected ( 95 % CI , -10.5 to 5.4 ; p = 0.531 ) . CONCLUSION In hematology patients , there was no evidence that 6- or 7-day PLTs were inferior to 2- to 5-day PLTs , as measured by proportion of patients with successful transfusions , bleeding events , or interval to next transfusion BACKGROUND Blood transfusion increases the risk of nosocomial infection in trauma patients . Specific patient- and transfusion-related risk factors are largely unknown . In this study , risk factors for developing a bacterial infection after transfusion of red blood cells ( RBC ) or platelets were determined in a cohort of transfused critically ill trauma patients . MATERIAL AND METHODS A retrospective study was conducted in a mixed medical-surgical Intensive Care Unit ( ICU ) of a level-1 university trauma centre , in trauma patients who received a RBC or platelet transfusion . Patients who developed a bacterial infection after transfusion were compared to transfused controls who did not develop such an infection . Multivariable logistic regression was used to determine risk factors for infection . RESULTS Of the 7,118 patients admitted to the ICU during the study period , 196 trauma patients met the inclusion criteria . An infection developed in 56 patients ( 29 % ) . Infection occurred irrespective of the administration of antibiotics as part of selective digestive tract decontamination , surgery status or Injury Severity Score . Transfusion of RBC stored for more than 14 days was associated with infection in trauma patients ( odds ratio 1.038 , [ 95 % CI : 1.01 - 1.07 ] , p=0.036 ) . Neither the amount of RBC nor that of platelets was associated with onset of infection . CONCLUSIONS Transfusion of RBC stored for more then 14 days is a risk factor for onset of bacterial infection after trauma , irrespective of the use of prophylactic antibiotics . Transfusion of platelets was not a risk factor . These results may contribute to design ing prospect i ve studies on transfusion of fresh RBC only in trauma patients Non-r and omised studies of the effects of interventions are critical to many areas of healthcare evaluation , but their results may be biased . It is therefore important to underst and and appraise their strengths and weaknesses . We developed ROBINS-I ( “ Risk Of Bias In Non-r and omised Studies - of Interventions ” ) , a new tool for evaluating risk of bias in estimates of the comparative effectiveness ( harm or benefit ) of interventions from studies that did not use r and omisation to allocate units ( individuals or clusters of individuals ) to comparison groups . The tool will be particularly useful to those undertaking systematic review s that include non-r and omised studies A nucleic acid-targeted photochemical treatment ( PCT ) using amotosalen HCl ( S-59 ) and ultraviolet A ( UVA ) light was developed to inactivate viruses , bacteria , protozoa , and leukocytes in platelet components . We conducted a controlled , r and omized , double-blinded trial in thrombocytopenic patients requiring repeated platelet transfusions for up to 56 days of support to evaluate the therapeutic efficacy and safety of platelet components prepared with the buffy coat method using this pathogen inactivation process . A total of 103 patients received one or more transfusions of either PCT test ( 311 transfusions ) or conventional reference ( 256 transfusions ) pooled , leukoreduced platelet components stored for up to 5 days before transfusion . More than 50 % of the PCT platelet components were stored for 4 to 5 days prior to transfusion . The mean 1-hour corrected count increment for up to the first 8 test and reference transfusions was not statistically significantly different between treatment groups ( 13,100 + /- 5400 vs 14,900 + /- 6200 , P = .11 ) . By longitudinal regression analysis for all transfusions , equal doses of test and reference components did not differ significantly with respect to the 1-hour ( 95 % confidence interval [ CI ] , -3.1 to 6.1 x 10(9)/L , P = .53 ) and 24-hour ( 95 % CI , -1.3 to 6.5 x 10(9)/L , P = .19 ) posttransfusion platelet count . Platelet transfusion dose , pretransfusion storage duration , and patient size were significant covariates ( P < .001 ) for posttransfusion platelet counts . Clinical hemostasis , hemorrhagic adverse events , and overall adverse events were not different between the treatment groups . Platelet components prepared with PCT offer the potential to further improve the safety of platelet transfusion using technology compatible with current methods to prepare buffy coat platelet components BACKGROUND Studies in cardiac surgery have reported increased postoperative morbidity and mortality after allogeneic red blood cell ( RBC ) transfusions . Whether platelet ( PLT ) and /or plasma transfusions are a marker for more concomitant RBC transfusions or are independently associated with complications after cardiac surgery is unknown . STUDY DESIGN AND METHODS Data from two r and omized controlled studies were combined to analyze the effects of PLT and /or plasma transfusions on postoperative infections , length of stay in the intensive care unit ( ICU ) , all-cause mortality , and mortality in the presence or absence of infections in the postoperative period . RESULTS After adjusting for confounding factors , plasma units and not RBC transfusions were associated with all-cause mortality . White blood cell (WBC)-containing RBC transfusions and PLT transfusions were associated with mortality occurring in the presence of or after infections . The number of ( WBC-containing ) RBC transfusions was also significantly associated with postoperative infections and with ICU stay for 4 or more days . CONCLUSION Although it is difficult to separate the effects of blood components , we found that in cardiac surgery , perioperative plasma transfusions are independently associated with all-cause mortality . WBC-containing RBC transfusions and PLT transfusions are independently associated with mortality in the presence of infections in the postoperative period . Future transf Output:	Conclusions PLT storage time does not appear to be associated with clinical outcomes , including bleeding , sepsis or mortality , in critically ill patients or haematology patients . The freshest PLTs ( less than 3 days ) were associated with a better CCI , although there was no impact on bleeding events , question ing the clinical significance of this association . However , there is an absence of evidence to draw definitive conclusions , especially in critically ill patients
MS21292	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Hospital-acquired delirium is a known risk factor for negative outcomes in patients admitted to the surgical intensive care unit ( SICU ) . Outcomes worsen as the duration of delirium increases . The purpose of this study was to evaluate the efficacy of a delirium prevention program and determine whether it decreased the incidence and duration of hospital-acquired delirium in older adults ( age>50 y ) admitted to the SICU . METHODS A prospect i ve pre- or post-intervention cohort study was done at an academic level I trauma center . Older adults admitted to the SICU were enrolled in a delirium prevention program . Those with traumatic brain injury , dementia , or 0 d of obtainable delirium status were excluded from analysis . The intervention consisted of multidisciplinary education , a pharmacologic protocol to limit medications associated with delirium , and a nonpharmacologic sleep enhancement protocol . Primary outcomes were incidence of delirium and delirium-free days/30 . Secondary outcomes were ventilator-free days/30 , SICU length of stay ( LOS ) , daily and cumulative doses of opioids ( milligram , morphine equivalents ) and benzodiazepines ( milligram , lorazepam equivalents ) , and time spent in severe pain ( greater than or equal to 6 on a scale of 1 - 10 ) . Delirium was measured using the Confusion Assessment Method for the ICU . Data were analyzed using Chi-squared and Wilcoxon rank sum analysis . RESULTS Of 624 patients admitted to the SICU , 123 met inclusion criteria : 57 preintervention ( 3/12 - 6/12 ) and 66 postintervention ( 7/12 - 3/13 ) . Cohorts were similar in age , gender , ratio of trauma patients , and Injury Severity Score . Postintervention , older adults experienced delirium at the same incidence ( pre 47 % versus 58 % , P=0.26 ) , but for a significantly decreased duration as indicated by an increase in delirium-free days/30 ( pre 24 versus 27 , P=0.002 ) . After intervention , older adults with delirium had more vent-free days ( pre 21 versus 25 , P=0.03 ) , shorter SICU LOS ( pre 13 [ median 12 ] versus 7 [ median 6 ] , P=0.01 ) and were less likely to be treated with benzodiazepines ( pre 85 % versus 63 % , P=0.05 ) with a lower daily dose when prescribed ( pre 5.7 versus 3.6 mg , P=0.04 ) . After intervention , all older adults spent less time in pain ( pre 4.7 versus 3.1 h , P=0.02 ) , received less total opioids ( pre 401 versus 260 mg , P=0.01 ) , and had shorter SICU LOS ( pre 9 [ median 5 ] versus 6 [ median 4 ] , P=0.04 ) . CONCLUSIONS Although delirium prevention continues to be a challenge , this study successfully decreased the duration of delirium for older adults admitted to the SICU . Our simple , cost-effective program led to improved pain and sedation outcomes . Older adults with delirium spent less time on the ventilator and all patients spent less time in the SICU BACKGROUND The objective of this study was to evaluate implementation of an innovative intervention design ed to prevent complications and stimulate early rehabilitation among frail elderly in patients . METHODS The program was implemented in April 2011 . A mixed- methods process evaluation and before-after study were performed . Primary effect outcomes included incidence of hospital-acquired delirium , cognitive decline , and decline in activities of daily living ( ADL ) during hospital stay . Secondary endpoints included ADL performance 3 months postdischarge , readmission , and caregiver burden . RESULTS One hundred ninety-one preintervention and 195 postintervention patients aged 70 years or older were included . Overall , no significant differences in primary endpoints were found . Mean ADL between discharge and follow-up improved ( 3.2 vs 5.7 , P = .058 ) . Caregivers rated burden of care lower at 3 months postdischarge ( .5 vs -.6 , P = .049 ) . CONCLUSIONS The CareWell in Hospital program was implemented satisfactorily . Although the low baseline delirium incidence ( 11 % ) , higher comorbidity , and an increasing learning curve during a restricted implementation period potentially influenced the overall effects , this integrated care program may have beneficial effects on outcomes among frail elderly surgical patients Importance The use of benzodiazepines to control agitation in delirium in the last days of life is controversial . Objective To compare the effect of lorazepam vs placebo as an adjuvant to haloperidol for persistent agitation in patients with delirium in the setting of advanced cancer . Design , Setting , and Participants Single-center , double-blind , parallel-group , r and omized clinical trial conducted at an acute palliative care unit at MD And erson Cancer Center , Texas , enrolling 93 patients with advanced cancer and agitated delirium despite scheduled haloperidol from February 11 , 2014 , to June 30 , 2016 , with data collection completed in October 2016 . Interventions Lorazepam ( 3 mg ) intravenously ( n = 47 ) or placebo ( n = 43 ) in addition to haloperidol ( 2 mg ) intravenously upon the onset of an agitation episode . Main Outcomes and Measures The primary outcome was change in Richmond Agitation-Sedation Scale ( RASS ) score ( range , −5 [ unarousable ] to 4 [ very agitated or combative ] ) from baseline to 8 hours after treatment administration . Secondary end points were rescue neuroleptic use , delirium recall , comfort ( perceived by caregivers and nurses ) , communication capacity , delirium severity , adverse effects , discharge outcomes , and overall survival . Results Among 90 r and omized patients ( mean age , 62 years ; women , 42 [ 47 % ] ) , 58 ( 64 % ) received the study medication and 52 ( 90 % ) completed the trial . Lorazepam + haloperidol result ed in a significantly greater reduction of RASS score at 8 hours ( −4.1 points ) than placebo + haloperidol ( −2.3 points ) ( mean difference , −1.9 points [ 95 % CI , −2.8 to −0.9 ] ; P < .001 ) . The lorazepam + haloperidol group required less median rescue neuroleptics ( 2.0 mg ) than the placebo + haloperidol group ( 4.0 mg ) ( median difference , −1.0 mg [ 95 % CI , −2.0 to 0 ] ; P = .009 ) and was perceived to be more comfortable by both blinded caregivers and nurses ( caregivers : 84 % for the lorazepam + haloperidol group vs 37 % for the placebo + haloperidol group ; mean difference , 47 % [ 95 % CI , 14 % to 73 % ] , P = .007 ; nurses : 77 % for the lorazepam + haloperidol group vs 30 % for the placebo + haloperidol group ; mean difference , 47 % [ 95 % CI , 17 % to 71 % ] , P = .005 ) . No significant between-group differences were found in delirium-related distress and survival . The most common adverse effect was hypokinesia ( 3 patients in the lorazepam + haloperidol group [ 19 % ] and 4 patients in the placebo + haloperidol group [ 27 % ] ) . Conclusions and Relevance In this preliminary trial of hospitalized patients with agitated delirium in the setting of advanced cancer , the addition of lorazepam to haloperidol compared with haloperidol alone result ed in a significantly greater reduction in agitation at 8 hours . Further research is needed to assess generalizability and adverse effects . Trial Registration clinical trials.gov Identifier : OBJECTIVES To determine whether a higher blood transfusion threshold would prevent new or worsening delirium symptoms in the hospital after hip fracture surgery . DESIGN Ancillary study to a r and omized clinical trial . SETTING Thirteen hospitals in the United States and Canada . PARTICIPANTS One hundred thirty-nine individuals hospitalized with hip fracture aged 50 and older ( mean age 81.5 ± 9.1 ) with cardiovascular disease or risk factors and hemoglobin concentrations of less than 10 g/dL within 3 days of surgery recruited in an ancillary study of the Transfusion Trigger Trial for Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair . INTERVENTION Individuals in the liberal treatment group received one unit of packed red blood cells and as much blood as needed to maintain hemoglobin concentrations at greater than 10 g/dL ; those in the restrictive treatment group received transfusions if they developed symptoms of anemia or their hemoglobin fell below 8 g/dL. MEASUREMENTS Delirium assessment s were performed before r and omization and up to three times after r and omization . The primary outcome was severity of delirium according to the Memorial Delirium Assessment Scale ( MDAS ) . The secondary outcome was the presence or absence of delirium defined according to the Confusion Assessment Method ( CAM ) . RESULTS The liberal group received a median two units of blood and the restrictive group zero units of blood . Hemoglobin concentration on Day 1 after r and omization was 1.4 g/dL higher in the liberal group . Treatment groups did not differ significantly at any time point or over time on MDAS delirium severity ( P = .28 ) or CAM delirium presence ( P = .83 ) . CONCLUSION Blood transfusion to maintain hemoglobin concentrations greater than 10 g/dL alone is unlikely to influence delirium severity or rate in individuals with hip fracture after surgery with a hemoglobin concentration less than 10 Introduction This study hypothesised that a reduction of sound during the night using earplugs could be beneficial in the prevention of intensive care delirium . Two research questions were formulated . First , does the use of earplugs during the night reduce the onset of delirium or confusion in the ICU ? Second , does the use of earplugs during the night improve the quality of sleep in the ICU ? Methods A r and omized clinical trial included adult intensive care patients in an intervention group of 69 patients sleeping with earplugs during the night and a control group of 67 patients sleeping without earplugs during the night . The research ers were blinded during data collection . Assignment was performed by an independent nurse research er using a computer program . Eligible patients had an expected length of stay in the ICU of more than 24 hours , were Dutch- or English-speaking and scored a minimum Glasgow Coma Scale of 10 . Delirium was assessed using the vali date d NEECHAM scale , sleep perception was reported by the patient in response to five questions . Results The use of earplugs during the night lowered the incidence of confusion in the studied intensive care patients . A vast improvement was shown by a Hazard Ratio of 0.47 ( 95 % confidence interval ( CI ) 0.27 to 0.82 ) . Also , patients sleeping with earplugs developed confusion later than the patients sleeping without earplugs . After the first night in the ICU , patients sleeping with earplugs reported a better sleep perception . Conclusions Earplugs may be a useful instrument in the prevention of confusion or delirium . The beneficial effects seem to be strongest within 48 hours after admission . The relation between sleep , sound and delirium , however , needs further research .Trial registration Current Controlled Trials IS RCT The objective of this study was to develop a prospect ively applicable method for classifying comorbid conditions which might alter the risk of mortality for use in longitudinal studies . A weighted index that takes into account the number and the seriousness of comorbid disease was developed in a cohort of 559 medical patients . The 1-yr mortality rates for the different scores were : " 0 " , 12 % ( 181 ) ; " 1 - 2 " , 26 % ( 225 ) ; " 3 - 4 " , 52 % ( 71 ) ; and " greater than or equal to 5 " , 85 % ( 82 ) . The index was tested for its ability to predict risk of death from comorbid disease in the second cohort of 685 patients during a 10-yr follow-up . The percent of patients who died of comorbid disease for the different scores were : " 0 " , 8 % ( 588 ) ; " 1 " , 25 % ( 54 ) ; " 2 " , 48 % ( 25 ) ; " greater than or equal to 3 " , 59 % ( 18 ) . With each increased level of the comorbidity index , there were stepwise increases in the cumulative mortality attributable to comorbid disease ( log rank chi 2 = 165 ; p less than 0.0001 ) . In this longer follow-up , age was also a predictor of mortality ( p less than 0.001 ) . The new index performed similarly to a previous system devised by Kaplan and Feinstein . The method of classifying comorbidity provides a simple , readily applicable and valid method of estimating risk of death from comorbid disease for use in longitudinal studies . Further work in larger population s is still required to refine the approach because the number of patients with any given condition in this study was relatively small Background : Major depression is a frequent and serious disorder in older medical in patients . Because the condition goes undetected and untreated in most of these patients , Output:	Conclusion : Non-pharmacological delirium interventions have frequently excluded and under-characterised people requiring palliative care and infrequently reported their outcomes
MS21293	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The objective of the present study was to compare three methods of cryotherapy in healthy non-pregnant women . This is a r and omized controlled clinical trial that was conducted by 32 undergraduates of a private nursing college in the city of Sao Paulo , divided into three groups ( iced water , soft ice , ice gel ) . The temperatures were verified ( axillary , thigh , of the three ice packs ) between zero and twenty minutes . The temperatures of the packs were the following : soft ice , from negative 9 degrees C to 2 degrees C ; iced water , from 0 degrees C to 8 degrees C ; and ice gel from negative 11 degrees C to 2 degrees C. There was a significant difference between the average thigh temperature values at 10 minutes ( p = 0.007 ) , 15 minutes ( p = 0.003 ) and 20 minutes ( p = 0.005 ) . The gel was the most efficient cooling method . The three cryotherapy methods achieved the recommended temperature for analgesia and may be tested in women with perineal pain after childbirth Systematic review s of r and omized controlled trials have demonstrated that episiotomies should not be performed routinely and that performing episiotomies in no more than 10 % of nulliparas being delivered vaginally would be safe . Episiotomy rates are reported for nulliparous and multiparous women in hospitals in Argentina Brazil Bolivia Chile the Democratic Republic of Congo Ecuador India Tibet Uruguay Venezuela and Zambia . These hospitals are part of the National Institute of Child Health and Human Development ’s Global Network for Women ’s and Children ’s Health Research . Data were collected using a survey form completed by investigators at 7 sites between April and December 2003 . All sites collected hospital-based data extracted from routine labor and delivery logbooks or from labor and delivery records . A site refers to an investigative team reporting data from 1 or more countries participating in the Global Network . Episiotomy rates are reported both by site and by mean rates and ranges across sites . ( excerpt The effect of cold sitz baths for relieving perineal pain in the postpartum period after an episiotomy was evaluated . Forty patients took both cold and warm sitz baths with r and om assignment of the initial bath . Patients rated the degree of perineal pain before and after each sitz bath and at half-hour and one-hour intervals after each bath . A pain scale using 0 - 5 , 0 representing no pain and 5 representing extreme pain , was used . Analysis of pain scale scores using a two-way analysis of variance with replications showed that cold sitz baths were significantly more effective in relieving perineal pain . The greatest amount of pain relief was experienced immediately after the cold sitz baths BACKGROUND The full extent of genital tract trauma in spontaneous births is not well documented . The purpose of this study was to describe the range and extent of childbirth trauma and related postnatal pain using data from a large r and omized clinical trial of perineal management techniques ( n = 5471 ) . METHODS Descriptive analysis was conducted on trial participants who delivered spontaneously at term and were examined by their midwife after birth ( n = 5404 ) . Data are reported for sites of trauma , and the relation to episiotomy , suturing , and maternal reports of pain at 2 days , 10 days , and 3 months after birth . RESULTS Eighty-five percent of all women experienced some form of trauma , with first- or second-degree perineal lacerations occurring in two-thirds of women and outer vaginal tears occurring in one-half . Tears to the rectum and vaginal vault were more common with episiotomy . Nearly all unsutured trauma was restricted to perineal first- or second-degree , outer vaginal , and labial sites . Pain declined over time , and a gradient in pain was observed according to the site and complexity of trauma . CONCLUSIONS Genital tract trauma is extremely common with spontaneous vaginal birth . Effective measures to prevent or reduce its occurrence would benefit many new mothers OBJECTIVE To evaluate the effectiveness of st and ard regimes ( ice packs and Epifoam ) at relieving perineal trauma and compare these with a new cooling device ( maternity gel pad ) . DESIGN A r and omised controlled trial involving three treatment groups . The women were free to choose the time of initial application ( within four hours after delivery ) in all treatment groups and the number of subsequent treatments up to 48 hours after suturing . SETTING A midwifery unit in the north of Engl and and then continued in the women 's own homes . PARTICIPANTS 120 women who had undergone an instrumental delivery and had a 48 hours post-delivery stay in a postnatal ward . MEASUREMENTS AND FINDINGS The ordinal scale of none , mild , moderate and severe was used to determine the levels of perineal oedema and bruising at initial assessment ( less than 4 hours ) , 24 hours and at 48 hours , by use of a newly developed visual evaluating tool . Self-assessed pain was recorded using a 10-point visual analogue scale within four hours , at 24 hours , 48 hours , and finally at five days after suturing . Women 's opinions as to the effectiveness of their treatment was rated by use of a 5-point scale describing the categories ; poor , fair , good , very good and excellent . A high proportion of women had some perineal oedema at initial assessment . A statistically significant difference in the proportion of women with oedema was found between treatment groups at 48 hours ( p = 0.01 ) , which was in favour of the maternity gel pad group . This was particularly noticeable for women with initial levels of mild oedema ( p = 0.017 ) . Localised treatment with the gel pad caused a significant decrease in reported pain at 48 hours in women who initially demonstrated moderate or severe pain ( p = 0.048 ) . A significant increase in the proportion of women with some bruising was seen across all treatment groups from initial assessment , through 24 hours to 48 hours ( p < 0.0005 ) . The bruising was significantly less in the gel-pad group in women who initially had no bruising ( p = 0.021 ) . There was no statistically significant effect of treatment at other initial levels of severity for oedema , bruising or pain at 24 hours , 48 hours and five days ( for pain ) . Women in the gel-pad group rated the effectiveness of their localised treatment to be significantly higher than women in the other two treatment groups ( p < 0.0005 ) . KEY CONCLUSIONS This trial demonstrated that a high proportion of women experience perineal oedema , bruising and pain following an instrumental delivery , which continues for at least five days for perineal pain , despite oral analgesia . Maternity gel pads , which were specially design ed to cool the perineal region , were more effective in alleviating perineal trauma when compared with hospital st and ard regimens and were more highly rated by women The association between episiotomy and severe ( third- and fourth-degree ) perineal lacerations was studied in 24,114 women . The overall rates of severe lacerations were 8.3 and 1.5 % for primiparous and multiparous women , respectively . Women who had midline episiotomies were nearly 50 times more likely and women who had mediolateral episiotomies were over eight times more likely to suffer a severe laceration than were women who did not undergo an episiotomy . Severe lacerations were also more common after use of forceps , in occiput transverse and posterior presentations , among women with smaller pelvic outlet measurements or lower prepregnant weight , and with larger fetuses . The same factors that caused a woman to have an increased risk of laceration also made performance of an episiotomy more likely . After statistical adjustment for these risk factors , mediolateral episiotomy was associated with a 2.5-fold reduction in the risk of severe lacerations among primiparous women , and a statistically nonsignificant 2.4-fold increase among multiparous women , compared with no episiotomy . Midline episiotomy was associated with statistically significant 4.2- and 12.8-fold increases in the risk of lacerations among primiparous and multiparous women , respectively . We conclude that the risks and benefits of midline episiotomy should be evaluated in a r and omized clinical trial that compares policies of “ usual ” versus conservative use of episiotomy Ultrasound and pulsed electromagnetic energy therapies arc increasingly used for perineal trauma sustained during childbirth . The study included 414 women with moderate or severe perineal trauma r and omly allocated to receive active ultrasound , or active pulsed electromagnetic energy , or corresponding placebo therapies ; the allocation was double‐blind for each machine . Overall , more than 90 % thought that treatment made their problem better . There were no clear differences between the groups in outcome either immediately after treatment , or 10 days or 3 months postpartum , other than more pain associated with pulsed electromagnetic energy treatment at 10 days . Bruising looked more extensive after ultrasound therapy but then seemed to resolve more quickly . Neither therapy had an effect on perineal oedema or haemorrhoids . The place of these new therapies in postnatal care should be clarified by further controlled trials before they become part of routine care Perineal discomfort from episiotomy continues to be a problem for many postpartum women . The purpose s of this study were to compare the effect of ice bag and heat lamp for the relief of perineal discomfort and to identify the sustaining time of each effect . Forty women took ice bag and heat lamp with r and om assignment of initial therapy . Women rated the degree of perineal discomfort before and after each therapy and at half-hour , tow-hour and four-hour intervals after each therapy . A discomfort scale , 18 cm graphic rating scale , was used . The results of the study were as follows : 1 . The ice bag group showed significantly lower discomfort score than the heat lamp group at the half-hour and two-hour intervals after therapy . 2 . The ice bag group showed significantly lower discomfort score for 4hrs after than before therapy , but the heat lamp group did not show significantly lower discomfort score . 3 . Neither the type of episiotomy nor the previous experience of heat therapy influenced on the effect of ice bag relieving the perineal discomfort . Therefore ice bag was significantly more effective in relieving perineal discomfort than heat lamp . Subjective responses of patients who took both therapy were very favorable toward ice bag . I suggested that nurses should provide women with adequate information about the use of ice bag and encourage to apply ice bag instead of heat lamp after episiotomy in order to promote the relief of perineal discomfort and the healing of perineal wound Objective To compare the effect of two methods of perineal management used during spontaneous vaginal delivery on the prevalence of perineal pain reported at 10 days after birth BACKGROUND Perineal pain is one of the most common causes of maternal morbidity in the early puerperium . Several r and omized trials have shown that topical application of local anesthetics is effective in reducing postepisiotomy pain , but no r and omized study has assessed the efficacy of local anesthetics for other perineal trauma . This study investigated if topically applied 2 percent lignocaine gel was an effective treatment for this group of women . METHODS A double-blind placebo controlled trial was conducted in a regional teaching hospital in the northwest of Engl and . One hundred and forty-nine women who had sustained a first- or second-degree tear were allocated by sealed envelopes to the lignocaine gel or placebo group . The primary outcome was self-reported pain at 24 hours postdelivery as measured on a numerical rating scale ( pain score ) . Secondary outcomes included pain scores at 48 hours , the need for oral analgesia , and maternal satisfaction . Based on a pilot study , we calculated that 128 women were required to detect a 25 percent difference in pain scores between the two groups with 80 percent power ( alpha = 0.05 ) . The pain scores of women in each trial arm were compared using the unpaired t test and 95 percent confidence intervals . RESULTS Women using lignocaine gel had lower average pain scores , although this only reached statistical significance at 48 hours after delivery ( p = 0.023 ) . In general , women liked using the study gel . No difference was found in consumption of oral analgesia . CONCLUSIONS This study suggested that lignocaine gel may be effective on the second postnatal day . Further research is required to assess the optimum timing of this intervention and the population that would most benefit from its use Abstract Midwives ' management of postpartum perineal pain was surveyed in 50 r and omly selected English maternity units . First line management was usually oral analgesia ( 78 % ) although some units first offered local ice , hydrocortisone and pramoxine foam ( Epifoam ) , or witch hazel . Paracetamol was the oral analgesic of choice for mild perineal pain but there was wide variation in the choice of oral analgesia for more severe pain ; the most common practice was to use paracetamol in combination with a stronger analgesic . Ice was the most popular local treatment ( 84 % of units ) but hydrocortisone/pramoxine foam ( Epifoam ) and therapeutic ultrasound were also popular . Many of the therapies mentioned in the survey remain poorly evaluated . Further controlled trials are needed to clarify their place in postnatal care Thirty healthy patients undergoing lumbar spine surgery were r and omly assigned to one of two groups for postoperative pain relief . Group 1 received morphine via patient controlled analgesia and local cooling of the wound by an externally applied cooling pad while group 2 received patient controlled analgesia alone . There was a significant reduction in morphine consumption when local cooling was applied ( 18.6 mg versus 30.2 mg at 12h , 29.0 mg versus 49.6 mg at 24 h , p < 0.05 ) . Patients were also significantly more satisfied with their overall postoperative pain management when cooling therapy was used INTRODUCTION This study evaluated the effectiveness of an ice pack applied for 2 Output:	AUTHORS ' CONCLUSIONS There is only limited evidence to support the effectiveness of local cooling treatments ( ice packs , cold gel pads , cold/iced baths ) applied to the perineum following childbirth to relieve pain
MS21294	*TASK* the task is to summarize an input biomedical literature in six sentences *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 / Objectives : Growing evidence emerged about the role of diet in heart failure ( HF ) development , but data are sparse and inconclusive . We examined the association between a Mediterranean-style diet , its components and HF risk . Subjects/ Methods : Analyses were carried out in 24 008 middle-aged participants of the European Prospect i ve Investigation into Cancer and Nutrition (EPIC)-Potsdam ( Germany ) , including 209 incident HF cases within 8.2 years . The traditional Greek Mediterranean diet score ( tMED ) was used to assess dietary adherence . Cox ’s proportional hazards regression was applied to estimate the relationship between the adherence to the Mediterranean-style diet , its components and HF risk . Results : After adjustment for age , sex and energy intake , a 2-unit increment in the tMED was associated with 26 % lower risk of HF ( HR ( 95 % confidence interval ( CI ) ) : 0.76 ( 0.60–0.97 ) ) . After multivariable adjustment , this association was slightly attenuated and lost significance [ HR ( 95%CI ) : 0.82 ( 0.64–1.05 ) ] . Interestingly , we observed a significant association in multivariable adjusted models when milk products were excluded from the score ( HR ( 95 % CI ) : 0.75 ( 0.59–0.96 ) ) . Three score components were significantly associated with HF risk : alcohol ( HR ( 95%CI ) : 0.73 ( 0.55–0.97 ) for moderate versus low/high intakes ) , meat : 2.04 ( 1.17–3.55 ) and fish : 0.59 ( 0.36–0.95 ) , both for the highest versus the lowest quintile . Conclusions : The tMED was not significantly associated with HF risk , but low meat , high fish and moderate alcohol intake were inversely associated with HF risk in our non-Mediterranean population . Minor dietary changes could be valuable primary prevention measures , particularly the increase of fish consumption while reducing the intake of meat Previous studies have reported that high fat feeding in mild to moderate heart failure ( HF ) results in the preservation of contractile function . Recent evidence has suggested that preventing the switch from fatty acid to glucose metabolism in HF may ameliorate dysfunction , and insulin resistance is one potential mechanism for regulating substrate utilization . This study was design ed to determine whether peripheral and myocardial insulin resistance exists with HF and /or a high-fat diet and whether myocardial insulin signaling was altered accordingly . Rats underwent coronary artery ligation ( HF ) or sham surgery and were r and omized to normal chow ( NC ; 14 % kcal from fat ) or a high-fat diet ( SAT ; 60 % kcal from fat ) for 8 wk . HF + SAT animals showed preserved systolic ( + dP/dt and stroke work ) and diastolic ( -dP/dt and time constant of relaxation ) function compared with HF + NC animals . Glucose tolerance tests revealed peripheral insulin resistance in sham + SAT , HF + NC , and HF + SAT animals compared with sham + NC animals . PET imaging confirmed myocardial insulin resistance only in HF + SAT animals , with an uptake ratio of 2.3 ± 0.3 versus 4.6 ± 0.7 , 4.3 ± 0.4 , and 4.2 ± 0.6 in sham + NC , sham + SAT , and HF + NC animals , respectively ; the myocardial glucose utilization rate was similarly decreased in HF + SAT animals only . Western blot analysis of insulin signaling protein expression was indicative of cardiac insulin resistance in HF + SAT animals . Specifically , alterations in Akt and glycogen synthase kinase-3β protein expression in HF + SAT animals compared with HF + NC animals may be involved in mediating myocardial insulin resistance . In conclusion , HF animals fed a high-saturated fat exhibited preserved myocardial contractile function , peripheral and myocardial insulin resistance , decreased myocardial glucose utilization rates , and alterations in cardiac insulin signaling . These results suggest that myocardial insulin resistance may serve a cardioprotective function with high fat feeding in mild to moderate HF Objective To investigate enteral nutrition ’s effect on serum inflammatory factors and the cardiac function of malnourished elderly patients with heart failure . Patients and methods A total of 105 elderly patients with heart failure were r and omly divided into 3 groups : Treatment Group A , Treatment Group B , and the Control Group ( Group C ) , each group having 35 patients and being administered conventional heart failure treatment . Group A was treated with 500 mL·d−1 of enteral nutrition for 1 month . Group B was given the same dose of enteral nutrition for 3 months . The Control Group was given free diet . Nutritional risk screening 2002 was used to assess the nutritional status before and after the treatment for each group . New York Heart Association status was recorded as were left ventricular ejection fraction , plasma B-type natriuretic peptide , inteleukin-6 , C-reactive protein , and tumor necrosis factor-α . Results After the treatment , the body mass index , skinfold thickness of upper arm triceps , muscle circumference of the upper arm , upper arm muscle circumference , total protein , albumin , hemoglobin , and left ventricular ejection fraction in the treatment groups all increased , with relatively obvious relief of symptoms of heart failure . The levels of B-type natriuretic peptide , interleukin-6 , tumor necrosis factor-α , and C-reactive protein all rose to different extents ( P<0.05 ) and Treatment Group B showed more obvious improvement ( P<0.01 ) . Differences shown by the Control Group in each nutrition indicator , serum levels of inflammatory factors , and cardiac function had no statistical significance ( P>0.05 ) . Conclusion The use of enteral nutrition in conventional treatment of elderly patients with heart failure could improve not only patients ’ nutritional status and cardiac function , but also their immune function , thus reducing the levels of inflammatory factors . The longer the treatment period is , the more obvious the improvement in patients ’ cardiac function and inflammatory factors will be observed OBJECTIVES This study sought to investigate the effect of a multiple micronutrient supplement on left ventricular ejection fraction ( LVEF ) in patients with heart failure . BACKGROUND Observational studies suggest that patients with heart failure have reduced intake and lower concentrations of a number of micronutrients . However , there have been very few intervention studies investigating the effect of micronutrient supplementation in patients with heart failure . METHODS This was a r and omized , double-blind , placebo-controlled , parallel-group study involving 74 patients with chronic stable heart failure that compared multiple micronutrient supplementation taken once daily versus placebo for 12 months . The primary endpoint was LVEF assessed by cardiovascular magnetic resonance imaging or 3-dimensional echocardiography . Secondary endpoints were Minnesota Living With Heart Failure Question naire score , 6-min walk test distance , blood concentrations of N-terminal prohormone of brain natriuretic peptide , C-reactive protein , tumor necrosis factor alpha , interleukin-6 , interleukin-10 , and urinary levels of 8-iso-prostagl and in F2 alpha . RESULTS Blood concentrations of a number of micronutrients increased significantly in the micronutrient supplement group , indicating excellent compliance with the intervention . There was no significant difference in mean LVEF at 12 months between treatment groups after adjusting for baseline ( mean difference : 1.6 % , 95 % confidence interval : -2.6 to 5.8 , p = 0.441 ) . There was also no significant difference in any of the secondary endpoints at 12 months between treatment groups . CONCLUSIONS This study provides no evidence to support the routine treatment of patients with chronic stable heart failure with a multiple micronutrient supplement . ( Micronutrient Supplementation in Patients With Heart Failure [ MINT-HF ] ; NCT01005303 ) In animals , carbohydrate and fat composition during dietary interventions influenced cardiac metabolism , structure , and function . Because reduced-carbohydrate and reduced-fat hypocaloric diets are commonly used in the treatment of obesity , we investigated whether these interventions differentially affect left ventricular mass , cardiac function , and blood pressure . We r and omized 170 overweight and obese subjects ( body mass index , 32.9±4.4 ; range , 26.5–45.4 kg/m2 ) to 6-month hypocaloric diets with either reduced carbohydrate intake or reduced fat intake . We obtained cardiac MRI and ambulatory blood pressure recordings over 24 hours before and after 6 months . Ninety subjects completing the intervention period had a full cardiac MRI data set . Subjects lost 7.3±4.0 kg ( 7.9±3.8 % ) with reduced-carbohydrate diet and 6.2±4.2 kg ( 6.7±4.4 % ) with reduced-fat diet ( P<0.001 within each group ; P = not significant between interventions ) . Caloric restriction led to similar significant decreases in left ventricular mass with low-carbohydrate diets ( 5.4±5.4 g ) or low-fat diets ( 5.2±4.8 g ; P<0.001 within each group ; P = not significant between interventions ) . Systolic and diastolic left ventricular function did not change with either diet . The 24-hour systolic blood pressure decreased similarly with both interventions . Body weight change ( & bgr;=0.33 ; P=0.02 ) and percentage of ingested n-3 polyunsaturated fatty acids ( & bgr;=−0.27 ; P=0.03 ) predicted changes in left ventricular mass . In conclusion , weight loss induced by reduced-fat diets or reduced-carbohydrate diets similarly improved left ventricular mass in overweight and obese subjects over a 6-month period . However , n-3 polyunsaturated fatty acid ingestion may have an independent beneficial effect on left ventricular mass BACKGROUND AND AIMS Hospitalized patients with heart failure who are malnourished present a worse prognosis than those with an adequate nutritional status . We undertook this study to assess whether a nutritional intervention in malnourished hospitalized patients with heart failure benefits morbidity and mortality . METHODS A multicenter , r and omized , controlled clinical trial was conducted . A total of 120 malnourished hospitalized patients due to acute heart failure were r and omised to conventional heart failure treatment or conventional heart failure treatment combined with an individualized nutritional intervention . The primary endpoint of this study was a composite of all-cause death or readmission for worsening of HF , with a maximum follow-up of 12 months . Analysis was by intention to treat . RESULTS Recruitment was stopped early according to the study protocol after completing the follow-up of the first 120 patients enrolled ( 59 in the intervention group and 61 in the control group ) . Both groups were homogeneous in baseline characteristics . At 12 months , the primary outcome occurred in 27.1 % of patients in the intervention group and in 60.7 % of patients in the control group ( hazard ratio 0.45 ; 95 % confidence interval [ CI ] , 0.19 - 0.62 , p = 0.0004 ) . In total , 20.3 % of patients died in the intervention group and 47.5 % in the control group ( hazard ratio 0.37 , 95 % CI , 0.19 - 0.72 , p = 0.003 ) . Readmission due to heart failure was also lower in the intervention group ( 10.2 vs. 36.1 % , p = 0.001 ) . CONCLUSION Nutritional intervention in malnourished hospitalized patients with heart failure reduces the risk of death from any cause and the risk of readmission for worsening of heart failure ( Clinical Trial.govNCT01472237 ) Background Optimal macronutrient distribution of weight loss diets has not been established . The distribution of energy from carbohydrate and fat has been observed to promote differential plasma lipid responses in previous weight loss studies , and insulin resistance status may interact with diet composition and affect weight loss and lipid responses . Methods and Results Overweight and obese women ( n=245 ) were enrolled in a 1‐year behavioral weight loss intervention and r and omly assigned to 1 of 3 study groups : a lower fat ( 20 % energy ) , higher carbohydrate ( 65 % energy ) diet ; a lower carbohydrate ( 45 % energy ) , higher fat ( 35 % energy ) diet ; or a walnut‐rich , higher fat ( 35 % energy ) , lower carbohydrate ( 45 % energy ) diet . Blood sample s and data available from 213 women at baseline and at 6 months were the focus of this analysis . Triglycerides , total cholesterol , and high‐ and low‐density lipoprotein cholesterol were quantified and compared between and within groups . Triglycerides decreased in all study arms at 6 months ( P<0.05 ) . The walnut‐rich diet increased high‐density lipoprotein cholesterol more than either the lower fat or lower carbohydrate diet ( P<0.05 ) . The walnut‐rich diet also Output:	Some studies showed that the Mediterranean diet ( MedDiet ) had a beneficial effect on cardiac function , while others did not find any positive impact . Nutritional supplements and hypercaloric intake had positive effects on underweight HF patients , while hypocaloric diet was beneficial in obese HF patients improving glucose control and cardiac function . The effect of MedDiet in HF patients showed conflicting results . Changes in the dietary pattern can reduce the evolution of HF , considering not only the quality of food but also the caloric intake . The discriminant factor to prescribe a diet regime in HF patients is represented by body mass index ( BMI ) . A well-balanced caloric diet represents an effective therapy in overweight HF patients to reduce the mortality rate .
MS21295	*TASK* the task is to summarize an input biomedical literature in six sentences *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 frequency of the 235 T and 174 M alleles of the angiotensinogen gene , previously reported to be associated with hypertension in Caucasians and Japanese , was compared between 57 hypertensive African Americans and 130 normotensive African Americans sample d as part of a community survey of hypertension in the Chicago area . The frequency of the 235 T allele was unrelated to hypertension status ( cases , 83 % , control subjects , 82 % ) , as was true for the 174 M allele . Compared with Caucasians , the frequency of the 235 T allele was twice as high in this African American population , while the frequency of the 174 M allele was similar . Even higher frequencies of the 235 T allele ( 93 % ) were noted in a sample of 122 Nigerians . It appears that the 235 T allele is very common in population s of West African origin , although we found no evidence that it confers risk of hypertension Abstract —The genes of the renin-angiotensin system have been subjected to intense molecular scrutiny in cardiovascular disease studies , but their contribution to risk is still uncertain . In this study , we sample d 192 African American and 153 European American families ( 602 and 608 individuals , respectively ) to evaluate the contribution of variations in genes that encode renin-angiotensin system components of susceptibility to hypertension . We genotyped 25 single-nucleotide polymorphisms in the renin-angiotensin system genes ACE , AGT , AGTR1 , and REN . The family-based transmission/disequilibrium test was performed with each single-nucleotide polymorphism and with the multilocus haplotypes . Two individual single-nucleotide polymorphisms were significantly associated with hypertension among African Americans , and this result persisted when both groups were combined . The associations were confirmed in haplotype analysis for REN , AGTR1 , and ACE in African Americans . Consistent but less significant evidence was found in European Americans . We also r and omly sample d unrelated individuals across families to obtain 84 cases and 108 controls among the African Americans and 41 cases and 113 controls in the European Americans . Single-nucleotide polymorphism and haplotype analyses again showed consistent , albeit weaker , results . Thus , in this biracial population sample , we find evidence that interindividual variation in the renin-angiotensin system genes contributes to hypertension risk BACKGROUND The angiotensin II type 1 receptor A1166C polymorphism has been associated with increased risks of hypertension and myocardial infa rct ion in several small studies . We examined the association between this polymorphism and new-onset hypertension , blood pressure ( BP ) control , and incident cardiovascular events in a large population -based cohort of older adults . METHODS Eight hundred self-identified African Americans and 1,371 r and omly selected white participants in the Cardiovascular Health Study were genotyped . The median duration of follow-up was 8.1 years . RESULTS The A1166C polymorphism was not associated with new-onset hypertension , with BP control , or with incident cardiovascular events in the overall population . In white participants , the CC genotype was associated with higher baseline systolic BP and pulse pressure , compared to the AC or AA genotype . In whites with treated hypertension at baseline , compared to the AA genotype , the CC genotype was associated with increased risks of incident congestive heart failure ( hazard ratio = 2.5 , 95 % confidence interval [ CI ] 1.3 - 4.9 ) and incident ischemic stroke ( hazard ratio = 2.6 , 95 % CI 1.1 - 6.0 ) . These associations were not observed among white participants without treated hypertension , but the interaction of genotype with treated hypertension on ischemic stroke and heart failure was only marginally significant . CONCLUSIONS On the whole , in this large cohort of older adults , the A1166C polymorphism was not associated with BP control or incident cardiovascular events . The subgroup findings in treated hypertensives need to be confirmed in additional studies Output:	Concordance between these two population s was found for some SNPs .
MS21296	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Even with statins and other lipid-lowering therapy ( LLT ) , many patients with heterozygous familial hypercholesterolemia ( heFH ) continue to have elevated low-density lipoprotein cholesterol ( LDL-C ) levels . ODYSSEY HIGH FH ( NCT01617655 ) assessed the efficacy and safety of alirocumab , a proprotein convertase subtilisin/kexin type 9 monoclonal antibody , versus placebo in patients with heFH and LDL-C ≥ 160 mg/dl despite maximally tolerated statin ± other LLT . Methods Patients were r and omized to subcutaneous alirocumab 150 mg or placebo every 2 weeks ( Q2W ) for 78 weeks . The primary endpoint was percent change in LDL-C from baseline to week 24 . Results Mean baseline LDL-C levels were 196.3 mg/dl in the alirocumab ( n = 71 ) and 201.0 mg/dl in the placebo groups ( n = 35 ) . Significant mean ( st and ard error [ SE ] ) reductions in LDL-C from baseline to week 24 were observed with alirocumab ( −45.7 [ 3.5 ] % ) versus placebo ( −6.6 [ 4.9 ] % ) , a difference of −39.1 ( 6.0 ) % ( P < 0.0001 ) . Absolute mean ( SE ) LDL-C levels were reduced from baseline by 90.8 ( 6.7 ) mg/dl with alirocumab at week 24 , with reductions maintained to week 78 . Treatment-emergent adverse events were generally comparable between groups . Injection-site reactions were more frequent in the alirocumab group ( 8.3 % ) versus placebo ( 5.7 % ) ; most were mild in severity and did not result in study medication discontinuation . Conclusions In patients with heFH and very high LDL-C baseline levels despite maximally tolerated statin ± other LLT , alirocumab 150 mg Q2W demonstrated significant reductions in LDL-C levels with 41 % of patients achieving predefined LDL-C goals . Alirocumab was generally well tolerated BACKGROUND Efficacy and safety of alirocumab were compared with ezetimibe in hypercholesterolemic patients at moderate cardiovascular risk not receiving statins or other lipid-lowering therapy . METHODS In a Phase 3 , r and omized , double-blind , double-dummy study ( NCT01644474 ) , patients ( low-density lipoprotein cholesterol [ LDL-C ] 100 - 190 mg/dL , 10-year risk of fatal cardiovascular events ≥ 1%-<5 % [ systemic coronary risk estimation ] ) were r and omized to ezetimibe 10mg/day ( n=51 ) or alirocumab 75 mg subcutaneously ( via 1-mL autoinjector ) every 2 weeks ( Q2W ) ( n=52 ) , with dose up-titrated to 150 mg Q2W ( also 1 mL ) at week 12 if week 8 LDL-C was ≥ 70 mg/dL. Primary endpoint was mean LDL-C % change from baseline to 24 weeks , analyzed using all available data ( intent-to-treat approach , ITT ) . Analyses using on-treatment LDL-C values were also conducted . RESULTS Mean ( SD ) baseline LDL-C levels were 141.1 ( 27.1 ) mg/dL ( alirocumab ) and 138.3 ( 24.5 ) mg/dL ( ezetimibe ) . The 24-week treatment period was completed by 85 % of alirocumab and 86 % of ezetimibe patients . Least squares mean ( SE ) LDL-C reductions were 47 (3)% with alirocumab versus 16 (3)% with ezetimibe ( ITT ; p<0.0001 ) and 54 (2)% versus 17 (2)% ( on-treatment ; p<0.0001 ) . At week 12 , before up-titration , alirocumab 75 mg Q2W reduced LDL-C by 53 (2)% ( on-treatment ) . Injection site reactions were infrequent ( < 2 % and < 4 % of alirocumab and ezetimibe patients , respectively ) . CONCLUSIONS Alirocumab demonstrated significantly greater LDL-C lowering versus ezetimibe after 24 weeks with the lower 75 mg Q2W dose sufficient to provide ≥ 50 % LDL-C reduction in the majority of the patients . Adverse events were comparable between groups BACKGROUND AND AIMS In previous phase III studies , the PCSK9 monoclonal antibody alirocumab was administered at doses of 75 or 150 mg every 2 weeks ( Q2W ) . CHOICE I ( NCT01926782 ) evaluated 300 mg every 4 weeks ( Q4W ) in patients on either maximally tolerated statin or no statin , both ± other lipid-lowering therapies . METHODS CHOICE I included patients with hypercholesterolemia at moderate-to-very-high cardiovascular risk . Patients were r and omized to alirocumab 300 mg Q4W , 75 mg Q2W ( calibrator arm ) , or placebo for 48 weeks , with dose adjustment for either alirocumab arm to 150 mg Q2W at Week ( W ) 12 if at W8 LDL-C levels were > 70/100 mg/dL ( 1.8/2.6 mmol/L ) depending on cardiovascular risk or LDL-C reduction was < 30 % from baseline . Co- primary endpoints were percent LDL-C change from baseline to W24 , and to time-averaged LDL-C over W21 - 24 . RESULTS Approximately two-thirds of r and omized patients were receiving statins . At W12 , 14.7 % ( no statin ) and 19.3 % ( statin ) of patients receiving alirocumab 300 mg Q4W required dose adjustment . At W24 , significant LDL-C reductions from baseline were observed with alirocumab 300 mg Q4W : mean differences were -52.7 % ( no statin ; placebo : -0.3 % ) and -58.8 % ( statin ; placebo : -0.1 % ) . Average LDL-C reductions from baseline to W21 - 24 were also significantly greater with alirocumab 300 mg Q4W vs. placebo in patients not receiving ( -56.9 % vs. -1.6 % ) and receiving statin ( -65.8 % vs. -0.8 % ) . Treatment-emergent adverse event rates ranged from 61.1 to 75.0 % ( placebo ) and 71.5 to 78.1 % ( alirocumab 300 mg Q4W ) . CONCLUSIONS Alirocumab 300 mg Q4W is a viable additional treatment option in patients requiring LDL-C-lowering Aims Statins have modest adverse effects on glycaemic control . Alirocumab , a proprotein convertase subtilisin/kexin type 9 inhibitor , lowers low-density lipoprotein cholesterol . This study assessed the effects of alirocumab on new-onset diabetes and pre-diabetes incidence in individuals without diabetes at baseline . Methods and results Pooled analysis of 10 ODYSSEY Phase 3 trials ( n = 4974 ) of 24–104 weeks duration . Six trials ( n = 4211 ) were ≥52 weeks in length . Most patients received background maximally tolerated statin . Alirocumab effect on the rate of diabetes-related treatment-emergent adverse events ( TEAEs ) , and /or fasting plasma glucose ( FPG ) and glycated haemoglobin A1C ( HbA1C ) was measured at baseline and every 12–24 weeks . Transition to diabetes analysis combined TEAE and FPG/HbA1C laboratory data . At baseline , 30.7 % of individuals had diabetes and were excluded from the current analysis . The remaining 3448 individuals without diabetes had pre-diabetes ( 39.6 % ) or were normoglycaemic ( 29.7 % ) . The hazard ratio ( HR ; 95 % confidence interval ) for diabetes-related TEAEs in alirocumab was 0.64 ( 0.36–1.14 ) vs. placebo and 0.55 ( 0.22–1.41 ) vs. ezetimibe . The HR associated for transition from pre-diabetes to new-onset diabetes for alirocumab was 0.90 ( 0.63–1.29 ) vs. placebo and 1.10 ( 0.57–2.12 ) vs. ezetimibe . Mean change in FPG/HbA1C over time showed no difference between treatment groups in patients without diabetes . Conclusions There was no evidence of an effect of alirocumab on transition to new-onset diabetes in 3448 individuals without diabetes at baseline with a follow-up period of 6–18 months , compared to either placebo or ezetimibe . Longer follow-up with larger number of individuals is needed to conclusively rule out an effect Aims To assess long-term ( 78 weeks ) alirocumab treatment in patients with heterozygous familial hypercholesterolaemia ( HeFH ) and inadequate LDL-C control on maximally tolerated lipid-lowering therapy ( LLT ) . Methods and results In two r and omized , double-blind studies ( ODYSSEY FH I , n = 486 ; FH II , n = 249 ) , patients were r and omized 2 : 1 to alirocumab 75 mg or placebo every 2 weeks ( Q2W ) . Alirocumab dose was increased at Week 12 to 150 mg Q2W if Week 8 LDL-C was ≥1.8 mmol/L ( 70 mg/dL ) . Primary endpoint ( both studies ) was percentage change in calculated LDL-C from baseline to Week 24 . Mean LDL-C levels decreased from 3.7 mmol/L ( 144.7 mg/dL ) at baseline to 1.8 mmol/L ( 71.3 mg/dL ; −57.9 % vs. placebo ) at Week 24 in patients r and omized to alirocumab in FH I and from 3.5 mmol/L ( 134.6 mg/dL ) to 1.8 mmol/L ( 67.7 mg/dL ; −51.4 % vs. placebo ) in FH II ( P < 0.0001 ) . These reductions were maintained through Week 78 . LDL-C < 1.8 mmol/L ( regardless of cardiovascular risk ) was achieved at Week 24 by 59.8 and 68.2 % of alirocumab-treated patients in FH I and FH II , respectively . Adverse events result ed in discontinuation in 3.4 % of alirocumab-treated patients in FH I ( vs. 6.1 % placebo ) and 3.6 % ( vs. 1.2 % ) in FH II . Rate of injection site reactions in alirocumab-treated patients was 12.4 % in FH I and 11.4 % in FH II ( vs. 11.0 and 7.4 % with placebo ) . Conclusion In patients with HeFH and inadequate LDL-C control at baseline despite maximally tolerated statin ± other LLT , alirocumab treatment result ed in significant LDL-C lowering and greater achievement of LDL-C target levels and was well tolerated . Clinical trial registration Cinicaltrials.gov ( identifiers : NCT01623115 ; NCT01709500 ) CONTEXT Despite current st and ard of care , many patients at high risk of cardiovascular disease ( CVD ) still have elevated low-density lipoprotein cholesterol ( LDL-C ) levels . Alirocumab is a fully human monoclonal antibody inhibitor of proprotein convertase subtilisin/kexin type 9 . OBJECTIVE The objective of the study was to compare the LDL-C-lowering efficacy of adding alirocumab vs other common lipid-lowering strategies . DESIGN , PATIENTS , AND INTERVENTIONS Patients ( n = 355 ) with very high CVD risk and LDL-C levels of 70 mg/dL or greater or high CVD risk and LDL-C of 100 mg/dL or greater on baseline atorvastatin 20 or 40 mg were r and omized to one of the following : 1 ) add-on alirocumab 75 mg every 2 weeks ( Q2W ) sc ; 2 ) add-on ezetimibe 10 mg/d ; 3 ) double atorvastatin dose ; or 4 ) for atorvastatin 40 mg regimen only , switch to ro Output:	Meta-regression analyses showed that risk of NODM was not associated with baseline age , baseline body mass index ( BMI ) , proportion of men , treatment duration or percent LDL cholesterol reduction . CONCLUSIONS Alirocumab and evolocumab , two types of PCSK9-mAb approved by the US Food and Drug Administration and the European Medicines Agency , had no significant impact on NODM and glucose homeostasis , regardless of PCSK9-mAb type , participant characteristics , treatment duration , treatment method and differences in control treatment . Baseline age , BMI , proportion of men , treatment duration , and percent change of LDL cholesterol did not influence diabetes risk
MS21297	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: A group of 200 patients who presented in general practice with symptoms but no abnormal physical signs and in whom no definite diagnosis was made were r and omly selected for one of four consultations : a consultation conducted in a " positive manner , " with and without treatment , and a consultation conducted in a " non-positive manner , " called a negative consultation , with and without treatment . Two weeks after consultation there was a significant difference in patient satisfaction between the positive and negative groups but not between the treated and untreated groups . Similarly , 64 % of those receiving a positive consultation got better , compared with 39 % of those who received a negative consultation ( p = 0.001 ) and 53 % of those treated got better compared with 50 % of those not treated ( p = 0.5 ) This study looked at the possible harmful effects of detection and treatment for hypertension . Patients with borderline blood pressure ( diastolic 96 - 109 mmHg ) were r and omized into two groups : an intervention group receiving treatment for hypertension and a control group not told about any problem and left untreated . The morbidity in these two groups were studied for differences . During the period studied , the patients in the investigation group saw the doctor more frequently and had a larger number of diseases classified than the control group . When consultations involving hypertension and its follow up were excluded , however , no differences were demonstrable between the groups . Problem behaviour , psychosomatic and functional affections and symptom diagnoses were evenly distributed over the two groups . The difference in blood pressure between the two groups after completion of the study was not marked : the decrease in diastolic blood pressure averaged 7.6 mmHg in the control group versus 9.1 mmHg in the intervention group . In cases where the initial blood pressure values are only slightly raised , careful monitoring of blood pressure over a long period seems to be as effective as treatment for hypertension . The general practitioner should focus especially on anticipation in this sense BACKGROUND When initiating treatment , it has been shown that only one quarter of the physicians discuss potential side effects with patients . There are several possible reasons , but , in particular , many physicians are concerned that the power of suggestion may lead some patients to experience an increase in side effects if they are fully informed . Accordingly , this study was design ed to determine whether providing patients with information about potential side effects of new medications increases the reported incidence of those side effects . METHODS All clinic patients are r and omly assigned to one of four firms . Two firms served as the intervention group and two served as control groups . All patients receiving new prescriptions for the angiotensin-converting enzyme inhibitors , trimethoprim/sulfamethoxazole , or nonsteroidal anti-inflammatory drugs were recruited . Patients without telephones were excluded . Intervention patients received verbal instructions and a h and out describing the name , purpose , dose , and three most common side effects of the drug . Control patients received usual discharge instructions . Patients were interviewed 14 to 21 days later using a st and ardized question naire . RESULTS There was no difference in incidence of targeted side effects for specific medications between the study groups ( 38 % vs 37 % ) . Study groups were similar with regard to age , sex , financial status , and type of medication prescribed . CONCLUSION Informing patients of potential side effects prior to starting a new medication does not lead to an increased incidence of those side effects . This should not be a reason for physicians to avoid warning patients of potential side effects To examine whether written informed consent might influence the results of clinical trials the effect of placebo when given with or without informed consent to patients suffering from insomnia was studied . The study was a single blind observer blinded trial , and patients were paired according to sex , age , and hospital environment . R and omisation assigned the first patient of each pair to the control group ( without informed consent ) or the group to give informed consent . Of the 56 patients , 26 refused to give informed consent , and the age and sex distribution of these differed significantly ( p less than 0.02 ) from the 30 pairs of patients ultimately enrolled into the study . In this " biased " sample , the hypnotic activity of placebo was significantly higher in the control group ( p less than 0.05 ) . It is concluded that the informed consent procedure biases the results of clinical trials and might affect their general applicability We carried out two studies to determine the effects of feedback on subsequent blood pressure and heart rate readings in subjects without significant cardiovascular abnormalities . In both studies the subjects were r and omly assigned to be told that their blood pressure was normal or was high or to receive no feedback at all ; 3 minutes later another reading was taken and correct feedback provided . Study 1 was done in 114 patients who attended a family practice teaching unit for an office visit ; subjects taking cardioactive medication or with chronically elevated blood pressure ( diastolic pressure more than 95 mm Hg ) or known low pressure ( diastolic pressure less than 60 mm Hg ) were excluded . Half of the subjects received feedback from a nurse and the other half from a physician . We found no effect of type of feedback or type of practitioner on subsequent readings . No adaptation of diastolic blood pressure or heart rate took place , whereas a similar rest period in the laboratory consistently triggers cardiovascular adaptation . Given the field nature of the study it was not clear whether the intervention was not powerful or whether the practitioner-patient interactions diffused the effects of an otherwise powerful intervention . Therefore , a second study with the same design was carried out in a controlled laboratory setting with 61 university students who believed they were in the adaptation phase of an experimental stress protocol . The subjects did not interact with the experimenter , who provided only the initial feedback , via intercom . The findings replicated those of study 1 : type of feedback had no significant effect on subsequent blood pressure levels , and all types of feedback prevented cardiovascular adaptation . We recommend that patients be allowed to rest alone for at least 10 minutes before blood pressure is measured . Our findings suggest that practitioners need not be concerned about telling normotensive or borderline hypertensive patients that their blood pressure is elevated OBJECTIVE To ascertain whether the quality of physician-patient communication makes a significant difference to patient health outcomes . DATA SOURCES The MEDLINE data base was search ed for articles published from 1983 to 1993 using " physician-patient relations " as the primary medical subject heading . Several bibliographies and conference proceedings were also review ed . STUDY SELECTION R and omized controlled trials ( RCTs ) and analytic studies of physician-patient communication in which patient health was an outcome variable . DATA EXTRACTION The following information was recorded about each study : sample size , patient characteristics , clinical setting , elements of communication assessed , patient outcomes measured , and direction and significance of any association found between aspects of communication and patient outcomes . DATA SYNTHESIS Of the 21 studies that met the final criteria for review , 16 reported positive results , 4 reported negative ( i.e. , nonsignificant ) results , and 1 was inconclusive . The quality of communication both in the history-taking segment of the visit and during discussion of the management plan was found to influence patient health outcomes . The outcomes affected were , in descending order of frequency , emotional health , symptom resolution , function , physiologic measures ( i.e. , blood pressure and blood sugar level ) and pain control . CONCLUSIONS Most of the studies review ed demonstrated a correlation between effective physician-patient communication and improved patient health outcomes . The components of effective communication identified by these studies can be used as the basis both for curriculum development in medical education and for patient education programs . Future research should focus on evaluating such educational programs To determine whether informed consent in a therapeutic trial modifies the analgesic effect of naproxen and placebo , we conducted a prospect i ve , r and omised , single dose , placebo-controlled trial . Patients were r and omly selected to receive or not information concerning the study . All patients included were then given a single dose of naproxen and placebo according to a crossover , double-blind design . Forty-nine patients with mild or moderate cancer pain which did not need narcotic analgesics entered the study . Twenty-five received both treatments without any information and constituted the uninformed group . Twenty-four had a complete information about the trial ; six refused to participate . The 18 others constituted the informed-consent group . Visual analogue scales of pain before and 30 , 60 , 120 and 180 min after the intake of naproxen and placebo were recorded . As an analgesic , naproxen was more effective than placebo in both groups of patients ( p = 0.001 ) . For naproxen as well as for placebo , the analgesic effect was better in the informed-consent group compared to the uninformed group ( p = 0.012 ) . The difference in therapeutic activity between naproxen and placebo was moderately higher in the uninformed patients ( p = 0.08 ) . We concluded that , in contrast with parallel studies , giving information in a crossover , placebo-controlled trial may increase the apparent efficacy of both the tested agent and the placebo , and decrease the perceived difference the two The influence of four variables ( status of communicator of drug effects , attitude of dentist , attitude of dental technician , and message of drug effects ) on the obtainment of placebo effects in an oral surgery clinic was investigated . Dependent variables were ( 1 ) rating of pain experienced from m and ibular-block injection , ( 2 ) pre-post placebo state anxiety , and ( 3 ) pre-postplacebo fear of injection . Enthusiastic messages of drug effects produced statistically and clinical ly significant reductions in postplacebo fear of injection and state anxiety and markedly lower ratings of pain experienced during injection of local anesthetic . Although there was a strong tendency for positive placebo effects to occur when the dental staff was perceived as friendly and supportive , only the attitude factors obtained statistical significance . The status of the communicator accounted for very small portions of the variance Homeless adults often visit emergency departments and often leave dissatisfied . We tested whether compassionate care , by improving patient satisfaction , can alter subsequent use of emergency services . We identified 133 consecutive homeless adults visiting one inner-city emergency department who were not acutely psychotic , extremely intoxicated , unable to speak English , or medically unstable . Half were r and omly assigned to receive compassionate contact from trained volunteers . All patients otherwise had usual care and were followed for repeat visits to emergency departments . We found that rates of use were high , with patients making an average of seven visits a year ( 0.60 per month ) . More than a third of all patients made two or more visits within two days of each other . The average number of visits per month after intervention was significantly lower for patients who received compassionate care ( 0.43 vs 0.65 , p = 0.018 ) . Analyses adjusting for each patient 's previous rate of use confirmed that compassionate care led to a one third reduction in the number of return visits within one month ( 95 % CI 14 to 40 % ) . Compassionate management of selected homeless adults decreases repeat visits to the emergency department . One explanation is that patients tend to return frequently until they are satisfied with their treatment Edrophonium is a widely used provocative agent in the evaluation of noncardiac chest pain , with reported positivity rates of 30 - 55 % . The influence of a subjective response and psychological factors on test results have not been examined previously . A retrospective analysis was performed to compare positivity rates for three physicians in the same laboratory . This was followed by a prospect i ve study of 62 patients with noncardiac chest pain r and omized to two groups . Group 1 patients were told that intravenous medication was given to observe changes in the tracing . Group 2 patients were told that the injection was to elicit their usual pain . During the 2-yr retrospective review , 260 patients were tested . The positivity rate varied from 31.1 % with physician A to 20.2 % with physician B and 7.5 % for physician C ( p = 0.001 for A vs. C , and p = 0.04 for B vs. C ) . In the prospect i ve study , chest pain was elicited in nine of 62 patients ( 14.5 % ) . Two of the 29 patients in group 1 ( 6.9 % ) and seven of 33 patients in group 2 ( 21.2 % ) contributed to this result . Contraction amplitude and duration increased similarly in all groups . These data suggest that edrophonium testing may be influenced by coaching , that manometric changes are similar in positive and negative tests , and that the prevalence of positive tests is lower than previously reported This study evaluated the effects of placebo medication on pulmonary responses in asthmatics , and investigated the roles of expectancy and anxiety . Twelve adult asthmatics were recruited for a laboratory experiment described as a study of the effectiveness of a new bronchodilator . Distilled nebulized water was inhaled in each session . The solution was described as water in session 1 ( control ) , while in sessions 2 and 3 subjects were told that the nebulizer contained a chemical likely to cause chest tightness and wheezing ( bronchoconstrictive suggestion ) . Prior to the inhalation sequence in sessions 2 and 3 , subjects inhaled from an aerosol that they were told contained either a powerful new drug ( placebo ) or a non-active substance ( neutral ) . Pulmonary function was measured with the forced oscillation technique and spirometry , while autonomic parameters , anxiety and expectancies were also monitored . Pulmonary function deteriorated following the inhalations accompanied by bronchoconstrictive suggestion , and this effect was abolished by pre-treatment with placebo . Neither subject expectations nor changes in anxiety were associated with the experimental manipulations . The implication s of these results for theories of placebo action are considered The effects of an anorexigenic agent ( dextroamphetamine ) and a placebo on weight loss in 64 obese female patients were evaluated over a period of 4 weeks . Half of the patients were field dependent and half were field independent . This psychological categorization of the patients refers to individual differences in analytic functioning in perception that can be objective ly evaluated and appears to parallel personality trait differences that have been noted between placebo reactors and nonreactors . An investigational drug or known drug treatment condition was created . Data from the study showed that : ( 1 ) Pat Output:	INTERPRETATION There is much inconsistency regarding emotional and cognitive care , although one relatively consistent finding is that physicians who adopt a warm , friendly , and reassuring manner are more effective than those who keep consultations formal and do not offer reassurance
MS21298	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To evaluate the effect of the middle and junior high school Drug Abuse Resistance Education ( D.A.R.E. ) and D.A.R.E. Plus programs on drug use and violence . DESIGN R and omized controlled trial of 24 schools , with 3 conditions : D.A.R.E. only , D.A.R.E. Plus , and delayed program control . SETTING Schools and neighborhoods , primarily in Minneapolis-St Paul . PARTICIPANTS All seventh- grade students in 24 schools in the academic year 1999 - 2000 ( N = 6237 at baseline , 67.3 % were white , and there was 84.0 % retention at final follow-up ) . INTERVENTIONS The middle and junior high school D.A.R.E. curriculum in the 16 schools that received D.A.R.E. only and D.A.R.E. Plus . In the 8 schoolts that received D.A.R.E. Plus , additional components included a peer-led parental involvement classroom program called " On the VERGE , " youth-led extracurricular activities , community adult action teams , and postcard mailings to parents . The interventions were implemented during 2 school years , when the cohort was in the seventh and eighth grade s. MAIN OUTCOME MEASURES Self-reported tobacco , alcohol , and marijuana use ; multidrug use ; violence ; and victimization , assessed at the beginning and end of seventh grade and at the end of eighth grade . Growth curve analytic methods were used to assess changes over time by condition . RESULTS There were no significant differences between D.A.R.E. only and the controls ; significant differences among boys between D.A.R.E. Plus and controls for tobacco , alcohol , and multidrug use and victimization ; significant differences among boys between D.A.R.E. Plus and D.A.R.E. only in tobacco use and violence ; and no significant behavioral differences among girls . CONCLUSION D.A.R.E. Plus significantly enhanced the effectiveness of the D.A.R.E. curriculum among boys and was more effective than the delayed program controls , underscoring the potential for multiyear , multicomponent prevention programs and demonstrating sex differences in response to intervention programs BACKGROUND AND OBJECTIVE To develop a checklist of items measuring the quality of reports of r and omized clinical trials ( RCTs ) assessing nonpharmacological treatments ( NPTs ) . STUDY DESIGN AND SETTING The Delphi consensus method was used to select and reduce the number of items in the checklist . A total of 154 individuals were invited to participate : epidemiologists and statisticians involved in the field of methodology of RCTs ( n = 55 ) , members of the Cochrane Collaboration ( n = 41 ) , and clinicians involved in planning NPT clinical trials ( n = 58 ) . Participants ranked on a 10-point Likert scale whether an item should be included in the checklist . RESULTS Fifty-five experts ( 36 % ) participated in the survey . They were experienced in systematic review s ( 68 % were involved in the Cochrane Collaboration ) and in planning RCTs ( 76 % ) . Three rounds of the Delphi method were conducted to achieve consensus . The final checklist contains 10 items and 5 subitems , with items related to the st and ardization of the intervention , care provider influence , and additional measures to minimize the potential bias from lack of blinding of participants , care providers , and outcome assessors . CONCLUSIONS This tool can be used to critically appraise the medical literature , design NPT studies , and assess the quality of trial reports included in systematic review OBJECTIVES : Media Detective is a 10-lesson elementary school substance use prevention program developed on the basis of the message interpretation processing model design ed to increase children 's critical thinking skills about media messages and reduce intent to use tobacco and alcohol products . The purpose of this study was to conduct a short-term , r and omized , controlled trial to evaluate the effectiveness of Media Detective for achieving these goals . METHODS : Elementary schools were r and omly assigned to conditions to either receive the Media Detective program ( n = 344 ) or serve in a waiting list control group ( n = 335 ) . RESULTS : Boys in the Media Detective group reported significantly less interest in alcohol-br and ed merch and ise than boys in the control group . Also , students who were in the Media Detective group and had used alcohol or tobacco in the past reported significantly less intention to use and more self-efficacy to refuse substances than students who were in the control group and had previously used alcohol or tobacco . CONCLUSIONS : This evaluation provides evidence that Media Detective can be effective for substance use prevention in elementary school – aged children . Notably , media-related cognitions about alcohol and tobacco products are malleable and relevant to the development and maintenance of substance use behaviors during late childhood . The findings from this study suggest that media literacy – based interventions may serve as both a universal and a targeted prevention program that has potential for assisting elementary school children in making healthier , more informed decisions about use of alcohol and tobacco products The Life Education organization offers a drug education programme to an estimated one million Australian primary schoolchildren . It is believed the programme delays experimentation with or initiation into smoking , alcohol use and the taking of analgesics . This study examined the short-term public health effects on 3000 11- and 12-year-old students , of whom 1700 were exposed to 5 consecutive years of the programme . The other 1300 students were not exposed to the programme . After controlling for the known predictors of social drug use there was no evidence that Life Education students , when compared with students receiving conventional school-based drug education , were less likely to have smoked , were less likely to have drunk or were less likely to have used analgesics . Indeed , the evidence suggested that Life Education-students were slightly more likely to use these substances , and that the programme had different effects on boys ' and girls ' drug use . Given that these findings are consistent with previous research evaluating similar drug education programmes , it is hypothesized they are most likely to do with the design of the programme itself Background Smoking rates are projected to increase substantially in developing countries such as South Africa . Purpose The aim of this study was to test the efficacy of two contrasting approaches to school-based smoking prevention in South African youth compared to the st and ard health education program . One experimental program was based on a skills training/peer resistance model and the other on a harm minimization model . Method Thirty-six public schools from two South African provinces , KwaZulu-Natal and the Western Cape , were stratified by socioeconomic status and r and omized to one of three groups . Group 1 ( comparison ) schools ( n = 12 ) received usual tobacco use education . Group 2 schools ( n = 12 ) received a harm minimization curriculum in grade s 8 and 9 . Group 3 schools ( n = 12 ) received a life skills training curriculum in grade s 8 and 9 . The primary outcome was past month use of cigarettes based on a self-reported question naire . Result Five thous and two hundred sixty-six students completed the baseline survey . Of these , 4,684 ( 89 % ) completed at least one follow-up assessment . The net change in 30-day smoking from baseline to 2-year follow-up in the control group was 6 % compared to 3 % in both harm minimization ( HM ) and life skills training ( LST ) schools . These differences were not statistically significant . Intervention response was significantly moderated by both gender and race . The HM intervention was more effective for males , whereas the life skills intervention was more effective for females . For black African students , the strongest effect was evident for the HM intervention , whereas the strongest intervention effect for “ colored ” students was evident for the LST group . Conclusion The two experimental curricula both produced similar overall reductions in smoking prevalence that were not significantly different from each other or the control group . However , the impact differed by gender and race , suggesting a need to tailor tobacco and drug use prevention programs . More intensive intervention , in the classroom and beyond , may be needed to further impact smoking behavior This study developed and tested a gender-specific intervention for preventing substance abuse among adolescent girls . Delivered on CD-ROM by computer , the program was compared with a conventional substance abuse prevention program delivered live in a group setting . Seventh- grade girls in New York City middle schools completed pretests , and , by school , were r and omly assigned to receive either gender-specific computer intervention ( GSI ) or conventional intervention , and were posttested . Analyses of pretest to posttest gain scores showed GSI girls compared to girls receiving conventional intervention to possess a larger repertoire of stress-reduction methods , to report lower approval of cigarettes , alcohol , and drugs , to identify more unhealthy ways to deal with stress , to report lower likelihood of cigarette use or alcohol consumption if asked to do so by best friends , and to hold stronger plans to avoid cigarettes , alcohol , and drugs in the next year . These modest findings lend credence to the promise of gender-specific , computerized interventions for substance use prevention among adolescent girls The Media Ready Program was design ed as a middle school , media literacy education , preventive intervention program to improve adolescents ' media literacy skills and reduce their intention to use alcohol or tobacco products . In a short-term efficacy trial , schools in North Carolina were r and omly assigned to conditions ( Media Ready : n = 214 ; control : n = 198 ) . Boys in the Media Ready group reported significantly less intention to use alcohol in the future than did boys in the control group . Also , students in the Media Ready group who had used tobacco in the past reported significantly less intention to use tobacco in the future than did students in the control group who had previously used tobacco . Multilevel multiple mediation analyses suggest that the set of logical analysis Message Interpretation Processing variables mediated the program 's effect on students ' intentions to use alcohol or tobacco in the future BACKGROUND The Good Behavior Game ( GBG ) , a method of classroom behavior management used by teachers , was tested in first- and second- grade classrooms in 19 Baltimore City Public Schools beginning in the 1985 - 1986 school year . The intervention was directed at the classroom as a whole to socialize children to the student role and reduce aggressive , disruptive behaviors , confirmed antecedents of later substance abuse and dependence disorders , smoking , and antisocial personality disorder . This article reports on impact to ages 19 - 21 . METHODS In five poor to lower-middle class , mainly African American urban areas , three or four schools were matched and within each set r and omly assigned to one of three conditions : ( 1 ) GBG , ( 2 ) a curriculum- and -instruction program directed at reading achievement , or ( 3 ) the st and ard program . Balanced assignment of children to classrooms was made , and then , within intervention schools , classrooms and teachers were r and omly assigned to intervention or control . RESULTS By young adulthood significant impact was found among males , particularly those in first grade who were more aggressive , disruptive , in reduced drug and alcohol abuse/dependence disorders , regular smoking , and antisocial personality disorder . These results underline the value of a first- grade universal prevention intervention . REPLICATION : A replication was implemented with the next cohort of first- grade children with the same teachers during the following school year , but with diminished mentoring and monitoring of teachers . The results showed significant GBG impact for males on drug abuse/dependence disorders with some variation . For other outcomes the effects were generally smaller but in the predicted direction OBJECTIVE To examine the effectiveness of a drug abuse prevention program in reducing the initiation and escalation of smoking in a sample of predominantly minority junior high school girls . METHODS The 15-session prevention program teaches social resistance skills within the context of a broader intervention design ed to promote general personal and social competence skills , and is implemented in the seventh grade . Smoking rates in girls from 29 New York City public schools who received the program ( n = 1,278 ) were compared to smoking rates in a control group of girls ( n = 931 ) who did not . RESULTS Those who participated in the program were less likely to initiate smoking relative to controls , due in part to significant program effects on smoking intentions , smoking knowledge , perceived peer and adult smoking norms , drug refusal skills , and risk taking . Experimental smokers in the intervention group were less likely to escalate to monthly smoking relative to controls , due in part to significant program effects on smoking intentions . CONCLUSION A school-based drug abuse prevention approach previously found to be effective among white youth significantly reduced smoking initiation and escalation among urban minority girls Background : Studies of effectiveness of school-based prevention of substance misuse have generally overlooked gender differences . The purpose of this work was to analyse gender differences in the effectiveness of a new European school-based curriculum for prevention of substance misuse among adolescents . Methods : The European Drug Abuse Prevention ( EU-Dap ) trial took place in seven European countries during the school year 2004–05 . Schools were r and omly assigned to either a control group or a 12-session st and ardised curriculum ( “ Unplugged ” ) based on a comprehensive social influence model . The analytical sample consisted of 6359 students ( 3324 boys and 3035 girls ) . The use of cigarettes , alcohol and illicit drugs , adolescents ’ knowledge and opinions about substances , as well as social and personal skills were investigated through a self-completed anonymous question naire administered at enrolment and 3 months after the end of the programme . Adjusted Prevalence Odds Ratios were calculated as the measure of association between the intervention and behavioural outcomes using multilevel regression modelling . Results : At enrolment , boys were more likely than girls to have used cannabis and illicit drugs , whereas girls had a higher prevalence of cigarette smoking . At the follow-up survey , a significant association Output:	Conclusions There was no evidence that school-based smoking prevention programs have a significant effect on preventing adolescent girls from smoking .
MS21299	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Methamphetamine use is subject to severe criminal punishment in Japan and approximately 22 % of the prison population were confined for violations of the stimulants control law in 2009 . Although the high recidivism rate is also a problem , no systematic treatment has been conducted in prison . Therefore , the development of the prison-based treatment program is necessary . In this study , the prison-based program was developed based on the Matrix Model , which is the cognitive-behavioral treatment for amphetamine users developed in the US . The program was tailored in order to address the treatment needs of the Japanese amphetamine users considering Japanese culture and the prison climate . The r and omized controlled trial was conducted in order to evaluate the effectiveness the Japanese Matrix program ( J-MAT ) . 60 prisoners were r and omly assigned either to the J-MAT or the control groups and those who in the J-MAT group received the program once a week for 12 weeks . The abstinence rate could not be used as the outcome measure because the participants could not be followed after the release from prison due to the legal reasons . Therefore , the psychological variables including coping skills , self-efficacy and motivation were used as outcome measures , which are considered as the important predictive factors of abstinence . 93.3 % of the J-MAT participants completed the program . The coping skills of the treated prisoners were improved significantly after treatment comparing to the control ( F ( 1 , 27 ) = 9.03 , p < .001 ) , however other psychological variables were not significantly improved . The results suggested the effectiveness of the J-MAT because both treatment completion and coping skills are powerful predictors of abstinence . Further study is required and in which the participants should be followed after the completion of treatment in order to compare the relapse rates between the groups and to measure the long-term treatment gain BACKGROUND Despite its effectiveness , methadone maintenance is rarely provided in American correctional facilities . This study is the first r and omized clinical trial in the US to examine the effectiveness of methadone maintenance treatment provided to prisoners with pre-incarceration heroin addiction . METHODS A three-group r and omized controlled trial was conducted between September 2003 and June 2005 . Two hundred eleven Baltimore pre-release inmates who were heroin dependent during the year prior to incarceration were enrolled in this study . Participants were r and omly assigned to the following : counseling only : counseling in prison , with passive referral to treatment upon release ( n=70 ) ; counseling+transfer : counseling in prison with transfer to methadone maintenance treatment upon release ( n=70 ) ; and counseling+methadone : methadone maintenance and counseling in prison , continued in a community-based methadone maintenance program upon release ( n=71 ) . RESULTS Two hundred participants were located for follow-up interviews and included in the current analysis . The percentages of participants in each condition that entered community-based treatment were , respectively , counseling only 7.8 % , counseling+transfer 50.0 % , and counseling+methadone 68.6 % , p<.05 . All pairwise comparisons were statistically significant ( all ps<.05 ) . The percentage of participants in each condition that tested positive for opioids at 1-month post-release were , respectively , counseling only 62.9 % , counseling+transfer 41.0 % , and counseling+methadone 27.6 % , p<.05 , with the counseling only group significantly more likely to test positive than the counseling+methadone group . CONCLUSIONS Methadone maintenance initiated prior to or immediately after release from prison appears to have beneficial short-term impact on community treatment entry and heroin use . This intervention may be able to fill an urgent treatment need for prisoners with heroin addiction histories Exposure to sexual victimization is prevalent among persons with substance use disorders ( SUDs ) . Contingency management ( CM ) treatments utilize concrete and relatively immediate positive reinforcers to retain patients in treatment and reduce substance use , and CM may have particular benefits for patients with histories of sexual victimization . Using data from three r and omized trials of CM ( N = 393 ) , this study evaluated main and interactive effects of sexual abuse history and treatment condition ( st and ard care versus CM ) with respect to during treatment outcomes ( retention , proportion of negative urine sample s su bmi tted , and longest duration of abstinence ) and abstinence at a nine-month follow-up . Compared to patients without sexual abuse histories ( N = 316 ) , those with sexual abuse histories ( N = 77 ) su bmi tted a significantly higher proportion of negative sample s in treatment . In CM , but not in st and ard care , patients with sexual abuse histories achieved significantly longer duration s of abstinence during treatment than those without sexual abuse histories . Although sexual abuse history was not associated with abstinence at nine-month follow-up evaluations , longest duration of abstinence during treatment was significantly associated with this long-term outcome . Results suggest that SUD patients with sexual abuse histories may accrue particular benefits during CM treatment that are associated with long-term abstinence . ( PsycINFO Data base Record ( c ) 2011 APA , all rights reserved ) OBJECTIVE We used growth mixture modeling to examine heterogeneity in treatment response in a secondary analysis of 2 r and omized controlled trials testing multidimensional family therapy ( MDFT ) , an established evidence -based therapy for adolescent drug abuse and delinquency . METHOD The first study compared 2 evidence -based adolescent substance abuse treatments : individually focused cognitive-behavioral therapy and MDFT in a sample of 224 urban , low-income , ethnic minority youths ( average age = 15 years , 81 % male , 72 % African American ) . The second compared a cross-systems version of MDFT ( MDFT-detention to community ) with enhanced services as usual for 154 youths , also primarily urban and ethnic minority ( average age = 15 years , 83 % male , 61 % African American , 22 % Latino ) , who were incarcerated in detention facilities . RESULTS In both studies , the analyses supported the distinctiveness of 2 classes of substance use severity , characterized primarily by adolescents with higher and lower initial severity ; the higher severity class also had greater psychiatric comorbidity . In each study , the 2 treatments showed similar effects in the classes with lower severity/frequency of substance use and fewer comorbid diagnoses . Further , in both studies , MDFT was more effective for the classes with greater overall substance use severity and frequency and more comorbid diagnoses . CONCLUSIONS Results indicate that for youths with more severe drug use and greater psychiatric comorbidity , MDFT produced superior treatment outcomes OBJECTIVES To compare the efficacy of memantine with buprenorphine in the suppression of naloxone-precipitated acute withdrawal in heroin-dependent male subjects in an inpatient setting . SETTING Inpatient unit of tertiary level deaddiction facility . PARTICIPANTS Forty-five treatment-seeking heroin-dependent males . INTERVENTIONS Subjects stabilized on 650 mg of dextropropoxyphene for 5 days were r and omly divided into two groups on the sixth day : group A ( n=25 ) received 20 mg of memantine with buprenorphineplacebo , and group B ( n=20 ) received 2 mg of buprenorphine with memantine placebo . Acute withdrawals were precipitated with naloxone ( 0.4 mg , intravenously ) and were assessed using subjective and objective opioid withdrawal scales ( SOWS and OOWS ) and two separate visual analogue scales ( VASs ) for pain and dysphoria at baseline prior to test drug administration and again after the precipitation of acute withdrawal . MAIN OUTCOME MEASURES Severity ofprecipitated opioid withdrawals . RESULTS Baseline opioid withdrawal symptoms in both groups did not differ significantly . After the precipitation of acute withdrawal , there were no significant differences between subjects in both groups on OOWS and both VASs but showed significant difference on SOWS . When changes in ratings from baseline ( and after naloxone-precipitated acute withdrawal ) were compared between the two groups , a significant difference in the change in SOWS scores was observed with greater decrease in withdrawal scores in the buprenorphine group . CONCLUSIONS Memantine has comparable efficacy to buprenorphine in the suppression of objective signs of naloxone-precipitated acute opioid withdrawal ; however , its role in the suppression of subjective symptoms is debatable Group motivational interviewing ( MI ) interventions that target youth at-risk for alcohol and other drug ( AOD ) use may prevent future negative consequences . Youth in a teen court setting [ n=193 ; 67 % male , 45 % Hispanic ; mean age 16.6 ( SD=1.05 ) ] were r and omized to receive either a group MI intervention , Free Talk , or usual care ( UC ) . We examined client acceptance , and intervention feasibility and conducted a preliminary outcome evaluation . Free Talk teens reported higher quality and satisfaction ratings , and MI integrity scores were higher for Free Talk groups . AOD use and delinquency decreased for both groups at 3 months , and 12-month recidivism rates were lower but not significantly different for the Free Talk group compared to UC . Results contribute to emerging literature on MI in a group setting . A longer term follow-up is warranted CONTEXT Effective alternatives to long waiting lists for entry into methadone hydrochloride maintenance treatment are needed to reduce the complications of continuing heroin dependence and to increase methadone treatment entry . OBJECTIVE To compare the effectiveness of interim methadone maintenance with that of the usual waiting list condition in facilitating methadone treatment entry and reducing heroin and cocaine use and criminal behavior . DESIGN R and omized , controlled , clinical trial using 2 conditions , with treatment assignment on a 3:2 basis to interim maintenance-waiting list control . SETTING A methadone treatment program in Baltimore . PARTICIPANTS A total of 319 individuals meeting the criteria for current heroin dependence and methadone maintenance treatment . INTERVENTIONS Participants were r and omly assigned to either interim methadone maintenance , consisting of an individually determined methadone dose and emergency counseling only for up to 120 days , or referral to community-based methadone treatment programs . MAIN OUTCOME MEASURES Entry into comprehensive methadone maintenance therapy at 4 months from baseline ; self-reported days of heroin use , cocaine use , and criminal behavior ; and number of urine drug test results positive for heroin and cocaine at the follow-up interview conducted at time of entry into comprehensive methadone treatment ( or at 4 months from baseline for participants who did not enter regular treatment ) . RESULTS Significantly more participants assigned to the interim methadone maintenance condition entered comprehensive methadone maintenance treatment by the 120th day from baseline ( 75.9 % ) than those assigned to the waiting list control condition ( 20.8 % ) ( P<.001 ) . Overall , in the past 30 days at follow-up , interim participants reported significantly fewer days of heroin use ( P<.001 ) , had a significant reduction in heroin-positive drug test results ( P<.001 ) , reported spending less money on drugs ( P<.001 ) , and received less illegal income ( P<.02 ) than the waiting list participants . CONCLUSION Interim methadone maintenance results in a substantial increase in the likelihood of entry into comprehensive treatment , and is an effective means of reducing heroin use and criminal behavior among opioid-dependent individuals awaiting entry into a comprehensive methadone treatment program This r and omized trial evaluates whether automated telephony could be used to perform daily assessment s in paroled offenders ( N = 108 ) during their first 30 days after leaving prison . All subjects were called daily and answered assessment questions . Based on the content of their daily assessment s , subjects in the intervention group received immediate feedback and a recommendation by automated telephony , and their probation officers also received a daily report by email . The outcome variables were analyzed using linear mixed models . The intervention group showed greater improvement than the control group in the summary scores ( M = 9.6 , 95 % confidence interval [ CI ] = [ 0.5 , 18.7 ] , p = .038 ) , in mental symptoms ( M = 4.6 , CI = [ 0.2 , 9.0 ] , p = .042 ) , in alcohol drinking ( M = 0.8 , CI = [ 0.1 , 1.4 ] , p = .031 ) , in drug use ( M = 1.0 , CI = [ 0.5 , 1.6 ] , p = .000 ) , and in most stressful daily event ( M = 1.9 , CI = [ 1.1 , 2.7 ] , p = .000 ) . In conclusion , automated telephony may be used to follow up and to give interventions , result ing in reduced stress and drug use , in paroled offenders This study was design ed to fulfill a twofold purpose . First , based on the hope theory framework and previous research , a 16-session hope-based substance abuse treatment program to help female drug abusers achieve a better recovery was developed . Second , ANCOVA was used to test the effectiveness of this treatment model . The participants were 40 female drug offenders who were r and omly assigned into experimental and control groups . The 20 experimental group participants received 16 sessions of hope-based substance abuse treatment whereas the 20 control group members were put on the waiting list for another term of treatment . The results indicated that the members of the two groups had significant differences in their posttest scores for recovery goal setting and pursuing , pathway controlling , adequate energy , knowledge of the changing process , ability to cope , adequate cognition , emotion regulation , and self-esteem Extended-release naltrexone ( XR-NTX ) , an approved treatment for opioid or alcohol dependence , is Output:	A narrative summary of the findings identified that the interventions reported limited success with reducing self report drug use , but did have some impact on re-incarceration rates , but not re-arrest . In the single comparisons , we found moderate- quality evidence that therapeutic communities determine a reduction in re-incarceration but reported less success for outcomes of re-arrest , moderate quality of evidence and self report drug use .

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