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MS2900	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: PURPOSE To evaluate safety and efficacy of combined transarterial chemoembolization ( TACE ) with doxorubicin-eluting beads ( DEB ) and sorafenib in patients with advanced hepatocellular carcinoma ( HCC ) . PATIENTS AND METHODS A prospect i ve single-center phase II study was undertaken involving patients with unresectable HCC . The protocol involved sorafenib 400 mg twice per day combined with DEB-TACE . Safety and response were assessed . Results DEB-TACE in combination with sorafenib was successfully administered in 35 patients : mean age , 63 years ; Child 's A , 89 % ; Barcelona Clinic Liver Cancer stage C , 64 % ; Eastern Cooperative Oncology Group performance status of 0 and 1 , 46 % and 54 % , respectively ; and mean index tumor size , 7.7 cm ( st and ard deviation , ± 4.2 cm ) . Patients underwent 128 cycles of therapy ( sorafenib plus DEB-TACE , 60 cycles ; sorafenib alone , 68 cycles ) . Median number of cycles per patient was two ( range , one to five cycles ) ; median number of days treated with sorafenib was 71 ( range , 4 to 620 days ) . The most common toxicities during cycle one were fatigue ( 94 % ) , anorexia ( 67 % ) , alterations in liver enzymes ( 64 % ) , and dermatologic adverse effects ( 48 % ) . Although most patients experienced at least one grade 3 to 4 toxicity , most toxicities were minor ( grade 1 to 2 , 83 % v grade 3 to 4 , 17 % ) . Toxicity during cycle two was decreased . Over the course of the study , there were 40 sorafenib dose interruptions and 25 sorafenib dose reductions . Sorafenib plus DEB-TACE was associated with a disease control rate of 95 % ( Response Evaluation Criteria in Solid Tumors Group)/100 % ( European Association for the Study of the Liver [ EASL ] ) , with an objective response of 58 % ( EASL ) . CONCLUSION The combination of sorafenib and DEB-TACE in patients with unresectable HCC is well tolerated and safe , with most toxicities related to sorafenib . Toxicity is manageable with dose adjustment of sorafenib . Preliminary efficacy data are promising Summary Background Sorafenib is the sole molecular-targeted agent showing a survival benefit in patients with advanced hepatocellular carcinoma ( HCC ) . We evaluated the tolerability and effectiveness of a combination of S-1 with sorafenib in patients with advanced HCC . Methods S-1 was administered during days 1–14 and sorafenib was administered every day . This treatment was repeated every 21 days . In phase I , we determined the maximum tolerated dose ( MTD ) and dose-limiting toxicities ( DLTs ) . The dose of each drug was planned as follows : cohort 1 : S-1 48 mg/m2/day and sorafenib 400 mg/day , cohort 2a : S-1 48 mg/m2/day and sorafenib 800 mg/day , cohort 2b : S-1 64 mg/m2/day and sorafenib 400 mg/day , cohort 3 : S-1 64 mg/m2/day and sorafenib 800 mg/day , and cohort 4 : S-1 80 mg/m2/day and sorafenib 800 mg/day . In phase II , the patients were treated at the MTD to evaluate safety and efficacy . Results Nineteen patients were enrolled in phase I. One of the six patients in cohort 1 and one of the six patients in cohort 3 experienced DLT . None of the three patients in cohort 2a experienced DLT and three of the four patients in cohort 4 experienced DLT . Therefore , cohort 3 was considered the MTD . Subsequently , 26 patients were enrolled in phase II . The most common grade 3/4 toxicities were an increase of aspartate aminotransferase ( 38.5 % ) , thrombocytopenia ( 23.1 % ) , neutropenia ( 19.2 % ) , hyperbilirubinemia ( 15.4 % ) , an increase of alanine aminotransferase ( 15.4 % ) , hyponatremia ( 11.5 % ) , rash ( 11.5 % ) , and hypophosphatemia ( 11.5 % ) . Sudden death occurred in one patient ( 3.8 % ) . A patient ( 3.8 % ) had a partial response , 15 ( 57.7 % ) had stable disease , and 10 ( 38.5 % ) had progressive disease . The median times to progression and overall survival were 2.4 and 10.5 months , respectively . Conclusion The MTD of S-1 and sorafenib in patients with advanced HCC was 64 mg/m2/day and 800 mg/day , respectively . This dose/regimen demonstrated substantial clinical activity among patients with advanced HCC Purpose Sorafenib improves overall survival and time to progression of advanced hepatocellular ( aHCC ) patients such as demonstrated in 2 phase III trials . However , aHCC patients ’ outcome is still poor despite these results . In order to improve the efficacy of systemic treatment for aHCC , we evaluated the combination of sorafenib plus 5-fluorouacil infusion in a phase II trial . Methods Patients with aHCC not eligible for loco-regional therapies , Child-Pugh A-B , ECOG-PS 0 - 1 , and without history of anti-cancer systemic treatment were enrolled . Treatment schedule was : sorafenib 400 mg/bid continuously and continuum infusion of 5-fluorouracil 200 mg/sqm/daily day 1–14 every 3 weeks . Results Thirty-nine patients were enrolled : ECOG-PS 0 - 1 : 29 - 10 , Child-Pugh A-B : 36 - 3 . Grade 3/4 ( % ) toxicities included : diarrhea 5.1/0 , mucositis 20.5/2.6 , h and foot skin reaction 20.5/0 , skin rash 10.5/0 , hypertension 10.3/0 , hyperbilirubinemia 5.1/2.6 , glutamic-oxaloacetic transaminase increase 10.3/0 , glutamic-pyruvic transaminase increase 7.7/0 , cardiac toxicity ( one heart failure , two atrial fibrillation cases ) 7.7/0 , and bleeding ( melena ) in 2.6/0 . One partial response was observed . Stable disease was obtained in 46.2 % of patients with a median duration of 16.2 months . Median time to progression was 8 months ( CI 95 % = 5.7–10.4 ) , and median overall survival was 13.7 months ( CI 95 % = 9.5–17.9 ) . Conclusions The results show an encouraging disease control rate , time to progression , and overall survival . The combination of sorafenib and 5-fluorouracil was feasible , and the side effects were manageable for patients carefully selected for liver function and performance status Background In Japan , transarterial infusion chemotherapy using cisplatin ( CDDP-TAI ) is frequently used for advanced hepatocellular carcinoma ( HCC ) . Moreover , oral chemotherapy with S-1 , an oral fluoropyrimidine derivative , has also elicited promising responses in HCC patients . We determined the recommended dosage for CDDP-TAI plus S-1 combination therapy for advanced HCC . Methods Twelve Child – Pugh class A or B patients with advanced HCC who met the eligibility criteria were enrolled in this phase I trial . Patients received CDDP-TAI ( infusion , day 1 ) plus S-1 ( oral administration , days 1–21 ) every 5 weeks until disease progression . Results Cisplatin ( 65 mg/m2 ) was administered with S-1 at 50 mg · m-2 day-1 ( level 1 , 3 patients ) , 60 mg · m-2 day-1 ( level 2 , 3 patients ) , or 80 mg · m-2 day-1 ( level 3 , 6 patients ) . The total number of treatment courses was 25 ( median , 2 courses/patient ; range , 1–6 courses ) . Dose-limiting toxicity was not observed in any patient at any level ; therefore , the recommended dosage for cisplatin and S-1 in combination was level 3 . Grade 3 adverse events were elevated alanine aminotransferase levels ( 2 patients ) , elevated aspartate aminotransferase levels ( 2 patients ) , anemia ( 1 patient ) , and decreased platelet counts ( 1 patient ) . Median progression-free survival and overall survival were 73 days and 328 days , respectively . The disease control rate was 58 % ( 7/12 ) ; 17 % ( 2/12 ) of patients achieved partial response and 42 % ( 5/12 ) achieved stable disease . CDDP-TAI plus S-1 is safe for the treatment of HCC . Conclusion The recommended dosage for further evaluation of this combination therapy in phase II studies is 65 mg/m2 CDDP and 80 mg/m2 S-1.Trial registration UMIN ; number : BACKGROUND & AIMS Sorafenib , a multi-kinase inhibitor with anti-angiogenic activity , was recently approved for the treatment of advanced hepatocellular carcinoma ( HCC ) . Metronomic chemotherapy using tegafur/uracil ( 4:1 molar ratio ) , an oral fluoropyrimidine , has been shown to enhance the anti-tumor effect of anti-angiogenic agents in pre clinical models . This phase II study evaluated the efficacy and safety of combining metronomic tegafur/uracil with sorafenib in patients with advanced HCC . METHODS Patients with histologically- or cytologically-proven HCC and Child-Pugh class A liver function were treated with sorafenib ( 400 mg twice daily ) and tegafur/uracil ( 125 mg/m(2 ) based on tegafur twice daily ) continuously as first-line therapy for metastatic or locally advanced disease that could not be treated by loco-regional therapies . The primary endpoint was progression-free survival ( PFS ) . RESULTS The study enrolled 53 patients . Thirty-eight patients ( 72 % ) were hepatitis B surface antigen-positive . The median PFS was 3.7 months ( 95 % C.I. , 1.9 - 5.5 ) and the median overall survival was 7.4 months ( 95 % C.I. , 3.4 - 11.4 ) . According to RECIST criteria , 4 patients ( 8 % ) had a partial response and 26 patients ( 49 % ) had a stable disease . Major grade 3/4 toxicities included fatigue ( 15 % ) , abnormal liver function ( 13 % ) , elevated serum lipase ( 10 % ) h and -foot skin reaction ( HFSR ) ( 9 % ) , and bleeding ( 8 % ) . HFSR was the major adverse event result ing in dose reduction ( 19 % ) or treatment delay ( 21 % ) . CONCLUSIONS Metronomic chemotherapy with tegafur/uracil can be safely combined with sorafenib and shows preliminary activity to improve the efficacy of sorafenib in advanced HCC patients S‐1 , an oral fluoropyrimidine derivative , has been shown to be clinical ly effective against various solid tumors , and pre clinical studies have demonstrated activity against hepatocellular carcinoma . We conducted a phase I/II study in patients with advanced hepatocellular carcinoma to examine the pharmacokinetics , recommended dose , safety and efficacy of S‐1 . In phase I , the administered dose of S‐1 was approximately 64 mg/m2 per day in three patients ( level 1 ) and approximately 80 mg/m2 per day in six patients ( level 2 ) . There was no dose‐limiting toxicity at level 1 , but two patients had dose‐limiting toxicity at level 2 ( grade 3 anorexia and grade 2 rash requiring eight or more consecutive days of rest ) . The recommended dose was finally estimated to be 80 mg/m2 per day . There were no significant differences in the pharmacokinetics of S‐1 between patients with Child‐Pugh A and those with B. In phase II , five of 23 patients ( 21.7 % ) had partial responses . The median progression‐free survival and overall survival were 3.7 and 16.6 months , respectively . The most common toxicities of grade 3 or 4 were elevated serum aspartate aminotransferase levels , hypochromia and thrombocytopenia . In conclusion , S‐1 showed an acceptable toxicity profile and promising antitumor activity for hepatocellular carcinoma , warranting further evaluation in r and omized clinical trials . ( Cancer Sci 2010 ; 101 : 2606–2611 Summary Purpose Sorafenib is a multi-kinase inhibitor , which was approved as first-line treatment for patients with advanced hepatocellular carcinoma ( HCC ) . We conducted a phase 1 study of sorafenib plus S-1 in patients with advanced HCC . Experimental design We design ed to escalate S-1 at 4 different dose levels with fixed dose of sorafenib . Four dose levels were as follows : level 1 , D1 - Output:	CONCLUSION This systematic review suggests that S-1 plus sorafenib showed modest clinical efficacy and tolerable toxicity profile in patients with advanced HCC .
MS2901	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Imatinib mesylate ( IM ) is the treatment of choice in patients with newly diagnosed chronic myeloid leukemia ( CML ) , irrespectively of their age . Nevertheless , information regarding tolerability and responses in advanced-age patients , a subgroup in which co-morbidities and other factors may influence outcome , is scarce , since they were excluded from most clinical trials . In this observational study ( ELDERGLI ) , information regarding demographics , concomitant medication , physical examination , performance status , hemogram , biochemistry , hematologic , cytogenetic and molecular responses , time to progression , adverse events ( AE ) and severe adverse events ( SAE ) were prospect ively recorded in a series of 36 elderly patients with CML , with a median age of 76.6 years . Most patients had cardiovascular co-morbidities , especially hypertension . Regarding IM toxicity , around one third of patients required treatment interruptions because of adverse events , especially hematologic toxicity ( 66 % of cases that needed dose interruptions ) . When analyzing non hematologic adverse events , the most frequent ones were superficial edemas and GI symptoms . Of note , 9 of patients experienced an infection episode during the follow-up , and 4 were diagnosed during the study period of another type of cancer . Finally , cardiovascular events were reported in 7 patients , most of them with prior cardiovascular risk factors . Regarding responses , after 12 months of imatinib therapy , the rate of complete hematologic response ( CHR ) , complete cytogenetic response ( CCyR ) and major molecular response ( MMolR ) were 89 % , 72 % and 55 % respectively . In summary , IM display , in advanced-age patients with chronic phase CML , an efficacy and safety profile comparable to younger patients Gender-related aspects in chronic myeloid leukemia ( CML ) have not been studied well . We therefore analyzed 856 patients with Ph/BCR-ABL-positive CML from the German r and omized CML- studies I ( interferon α ( IFN ) vs hydroxyurea ( HU ) vs busulfan ) and II ( IFN+HU vs HU alone ) . The median observation time was 8.6 years . A total of 503 patients ( 59 % ) were male . Female patients were older ( 51 vs 46 years ; P<0.0001 ) , presented with lower hemoglobin ( 11.7 vs 12.5 g/dl ; P<0.0001 ) , higher platelet counts ( 459 vs 355 × 109/l ; P<0.0001 ) , smaller spleen size ( 3 vs 4 cm below costal margin ; P=0.0097 ) , a lower rate of additional cytogenetic aberrations ( 9 vs 15 % ; P=0.018 ) and a less favorable risk profile ( P=0.036 ) . The transplantation rate was 14 % for female ( n=48 ) and 22 % for male patients ( n=113 ) . Median survival was longer in female patients ( 58 vs 49 months ; P=0.035 ) mainly attributable to better survival in the low- and intermediate-risk groups and , independent from risk groups , in the HU group . These results were confirmed by matched-pair analyses based on German population data ( n=496 , 59 vs 45 months ; P=0.0006 ) . This is the first analysis of gender aspects in CML using r and omized trials . It demonstrates the relevance of analyses of gender differences in CML and in malignant disease at large The median age of chronic myeloid leukemia ( CML ) patients is ~60 years , and age is still considered an important prognostic factor , included in Sokal and EURO risk scores . However , few data are available about the long-term outcome of older patients treated with imatinib ( IM ) frontline . We analyzed the relationship between age and outcome in 559 early chronic-phase CML patients enrolled in 3 prospect i ve clinical trials of Gruppo Italiano Malattie Ematologiche dell'Adulto CML Working Party , treated frontline with IM , with a median follow-up of 60 months . There were 115 older patients ( ≥ 65 years ; 21 % ) . The complete cytogenetic and major molecular response rates were similar in the 2 age groups . In older patients , event-free survival ( 55 % vs 67 % ) , failure-free survival ( 78 % vs 92 % ) , progression-free survival ( 62 % vs 78 % ) , and overall survival ( 75 % vs 89 % ) were significantly inferior ( all P < .01 ) because of a higher proportion of deaths that occurred in complete hematologic response , therefore unrelated to CML progression ( 15 % vs 3 % , P < .0001 ) . The outcome was similar once those deaths were censored . These data show that response to IM was not affected by age and that the mortality rate linked to CML is similar in both age groups . This trial was registered at www . clinical trials.gov as # NCT00514488 and # NCT00510926 PURPOSE To determine the response rate to interferon-alpha ( IFN-alpha ) in patients with chronic myelogenous leukemia ( CML ) aged 60 years and older . PATIENTS AND METHODS Patients with CML aged 60 years and older included in all protocol s with INF-alpha therapy for chronic phase CML at the M.D. And erson Cancer Center were analyzed . They were treated with human leukocyte or recombinant human IFN-alpha 5x10(6 ) U/m2 daily alone or in combination with hydroxyurea or IFN gamma . The clinical characteristics of the patients were analyzed and their hematologic and cytogenetic responses to IFN-alpha and survival from the initiation of therapy were determined . Results were compared with those of younger patients treated in the same protocol s. Treatment-related toxicity was also analyzed . RESULTS Thirty-five of 274 ( 13 % ) patients included in trials of IFN-alpha-based regimens for CML were 60 years and older . Older patients had a higher percentage of bone marrow blasts ( P = 0.04 ) and basophils ( P = 0.09 ) than younger patients . Sixty-nine percent achieved a complete hematologic remission with IFN-alpha therapy , and 51 % had a cytogenetic response , which was major in 26 % and complete ( Philadelphia chromosome-positive cells = 0 % ) in 20 % , Their median survival was 64 months , and the estimated 5-year survival rate was 62 % . These results were not different from those in younger patients . Twenty-two patients ( 63 % ) had at least grade 2 toxicity requiring dose adjustment . The most frequent side effects were neurotoxicity in 31 % and chronic fatigue in 29 % . CONCLUSIONS Patients with CML 60 years of age and older respond well to IFN-alpha therapy , but experience more toxicity . This therapy should be considered for these patients if they are otherwise in good condition , with careful attention to IFN-alpha toxicity and its management Thirty-five patients with Ph+ CML aged more than 60 years were treated with imatinib . Twenty-four patients ( group A ) were in late chronic phase ( CP ) and eleven patients ( group B ) were in accelerated/blastic phase ( AP/BP ) . In group A , complete haematological response ( CHR ) was achieved by all patients ; seventeen patients ( 70.8 % ) attained a complete cytogenetic response ( CCR ) , one ( 4.1 % ) attained a partial CR , one ( 4.1 % ) a minor CR ( Ph+ 70 % ) and five ( 21 % ) were resistant ( Ph+ 100 % ) , toxicity was mild : seven patients had a transient cytopenia , three a skin reaction , one a moderate oedema and one muscular pain . After a median follow-up of 15 months , 1 patient died in progression and 23 patients are alive ( 2 in BP and 21 in persisting response ) . In group B , one patient died after 3 months in aplastic phase from sepsis , three patients were resistant and seven patients ( 63.7 % ) achieved CHR ; of these , four obtained CCR . After a median follow-up of 17 months , 4 patients have died from progressive disease , 6 are alive ; 1 in AP and 5 in CHR ( 4 of them being in CCR ) . Present data indicate that imatinib is safe also in elderly with clinical results as good as in younger patients Chronic myeloid leukemia ( CML ) in older patients has not been studied well . To assess the long-term outcome of older patients with Philadelphia- and /or BCR-ABL-positive CML , 199 patients aged > /=60 years representing 23 % of 856 patients enrolled in the German r and omized CML- studies I ( interferon alpha ( IFN ) vs hydroxyurea ( HU ) vs busulfan ( BU ) and II ( IFN+HU vs HU alone ) were analyzed after a median observation time of 7 years . In all , 45 patients were treated with Bu , 63 with HU , and 91 with IFN . The 5-year survival was 38 % in patients > /=60 years and 47 % in patients < 60 years ( P<0.001 ) . Whereas 5-year survival in chemotherapy-treated older patients was inferior to that in younger patients ( 33 vs 46 % , P=0.006 for HU and 29 vs 38 % , P=0.042 for Bu ) , no significant survival difference could be verified in IFN-treated patients ( 46 vs 53 % , P=0.077 ) . Calculation of age-adjusted , relative survival confirmed these results . Adverse effects of IFN were similar in both age groups , but IFN dosage to achieve treatment goals was lower in older patients . We conclude that the course of CML is not different in the elderly . They require lower IFN doses , achieve the same hematologic and cytogenetic response rates and the same survival advantage at comparable toxicity To assess the effect of age on response and compliance to treatment in patients with chronic myeloid leukemia ( CML ) we performed a sub- analysis within a phase II trial of the GIMEMA CML Working Party ( CML/002/STI571 ) . Since the WHO cut-off age to define an older patient is 65 years , among the 284 patients considered , we identified 226 ( 80 % ) younger patients ( below 65 years ) and 58 ( 20 % ) older patients ( above 65 years ) before starting imatinib . Response rates ( hematologic and cytogenetic ) were lower in the older age group but the probabilities of progression-free survival and overall survival ( median observation time 3 years ) were the same . Moreover , among complete cytogenetic responders , no differences were found in the level of molecular response between the two age groups . As might be expected , older patients experienced more adverse events , both hematologic and non-hematologic : this worsened compliance did not , however , prevent a long-term outcome similar to that of younger patients Output:	Imatinib in newly diagnosed older patients showed similar rate of cytogenetic and molecular responses compared to younger patients . The aim of this review is , through the revision of published data , to highlight the fact that elderly CML patients can benefit from target therapy with limited adverse events
MS2902	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Gene-based vaccination using prime/boost regimens protects animals and humans against malaria , inducing cell-mediated responses that in animal models target liver stage malaria parasites . We tested a DNA prime/adenovirus boost malaria vaccine in a Phase 1 clinical trial with controlled human malaria infection . Methodology /Principal Findings The vaccine regimen was three monthly doses of two DNA plasmids ( DNA ) followed four months later by a single boost with two non-replicating human serotype 5 adenovirus vectors ( Ad ) . The constructs encoded genes expressing P. falciparum circumsporozoite protein ( CSP ) and apical membrane antigen-1 ( AMA1 ) . The regimen was safe and well-tolerated , with mostly mild adverse events that occurred at the site of injection . Only one AE ( diarrhea ) , possibly related to immunization , was severe ( Grade 3 ) , preventing daily activities . Four weeks after the Ad boost , 15 study subjects were challenged with P. falciparum sporozoites by mosquito bite , and four ( 27 % ) were sterilely protected . Antibody responses by ELISA rose after Ad boost but were low ( CSP geometric mean titer 210 , range 44–817 ; AMA1 geometric mean micrograms/milliliter 11.9 , range 1.5–102 ) and were not associated with protection . Ex vivo IFN-γ ELISpot responses after Ad boost were modest ( CSP geometric mean spot forming cells/million peripheral blood mononuclear cells 86 , range 13–408 ; AMA1 348 , range 88–1270 ) and were highest in three protected subjects . ELISpot responses to AMA1 were significantly associated with protection ( p = 0.019 ) . Flow cytometry identified predominant IFN-γ mono-secreting CD8 + T cell responses in three protected subjects . No subjects with high pre-existing anti-Ad5 neutralizing antibodies were protected but the association was not statistically significant . Significance The DNA/Ad regimen provided the highest sterile immunity achieved against malaria following immunization with a gene-based subunit vaccine ( 27 % ) . Protection was associated with cell-mediated immunity to AMA1 , with CSP probably contributing . Substituting a low seroprevalence vector for Ad5 and supplementing CSP/AMA1 with additional antigens may improve protection . Trial Registration Clinical Trials.govNCT00870987 rDEN2/4Δ30(ME ) is an attenuated chimeric dengue virus in which the prM and E structural proteins of the DEN4 c and i date vaccine rDEN4∆30 have been replaced by those of the prototypic DEN2 NGC virus . rDEN2/4Δ30(ME ) was evaluated at a dose of 1,000 PFU in 20 healthy dengue-naïve adult volunteers . Eight volunteers received placebo . Volunteers were monitored closely for adverse events and serum was collected for determination of the level and duration of viremia and neutralizing antibody response . The vaccine was well tolerated by all volunteers . The most common adverse events observed were a transient asymptomatic rash and mild neutropenia . All vaccinees seroconverted to DEN2 and maintained significant antibody titers throughout the six-month trial duration . Eleven vaccinees had vaccine virus recovered from the blood during the study . RNA derived from virus isolates obtained from viremic volunteers was sequenced for confirmation of retention of the ∆30 mutation in the 3 ´ UTR . The Δ30 mutation remained unchanged in each isolate , confirming the stability of the Δ30 mutation . Further evaluation of this vaccine in a tetravalent formulation is warranted Tuberculosis ( TB ) is a global public health problem exacerbated by the HIV epidemic . Here we evaluate a c and i date TB vaccine , MVA85A , in a Phase I study in HIV-infected adults in Senegal . 24 patients were enrolled : Group 1∶12 , antiretroviral therapy ( ART ) naïve , adults , with CD4 counts > 300 and HIV RNA load < 100 000 copies/ml . Group 2∶12 adults , stable on ART , with CD4 counts > 300 , and an undetectable HIV RNA load . Safety was evaluated by occurrence of local and systemic adverse events ( AEs ) and by monitoring of CD4 count , HIV RNA load , haematology and biochemistry . Immunogenicity was evaluated by ex-vivo interferon-gamma ELISpot assay . 87.7 % of AEs were mild ; 11.6 % were moderate ; and 0.7 % were severe . 29.2 % of AEs were systemic ; 70.8 % were expected local AEs . There were no vaccine-related Serious Adverse Events ( SAEs ) or clinical ly significant effects on HIV RNA load or CD4 count . In ART naive subjects , the first MVA85A immunisation induced a significant immune response at 1 and 4 weeks post-immunisation , which contracted to baseline by 12 weeks . Durability of immunogenicity in subjects on ART persisted out to 24 weeks post-vaccination . A second dose of MVA85A at 12 months enhanced immunogenicity in ART naïve subjects . Subjects on ART had higher responses after the first vaccination compared with ART naïve subjects ; responses were comparable after 2 immunisations . In conclusion , MVA85A is well-tolerated and immunogenic in HIV-infected subjects in Senegal . A two dose regimen in ART naïve subjects is comparable in immunogenicity to a single dose in subjects on ART . Clinical trials.gov trial identifier NCT00731471 Background Inhibition of parasite growth is a major objective of blood-stage malaria vaccines . The in vitro assay of parasite growth inhibitory activity ( GIA ) is widely used as a surrogate marker for malaria vaccine efficacy in the down- selection of c and i date blood-stage vaccines . Here we report the first study to examine the relationship between in vivo Plasmodium falciparum growth rates and in vitro GIA in humans experimentally infected with blood-stage malaria . Methods In this phase I/IIa open-label clinical trial five healthy malaria-naive volunteers were immunised with AMA1/C1-Alhydrogel+CPG 7909 , and together with three unvaccinated controls were challenged by intravenous inoculation of P. falciparum infected erythrocytes . Results A significant correlation was observed between parasite multiplication rate in 48 hours ( PMR ) and both vaccine-induced growth-inhibitory activity ( Pearson r = −0.93 [ 95 % CI : −1.0 , −0.27 ] P = 0.02 ) and AMA1 antibody titres in the vaccine group ( Pearson r = −0.93 [ 95 % CI : −0.99 , −0.25 ] P = 0.02 ) . However immunisation failed to reduce overall mean PMR in the vaccine group in comparison to the controls ( vaccinee 16 fold [ 95 % CI : 12 , 22 ] , control 17 fold [ CI : 0 , 65 ] P = 0.70 ) . Therefore no impact on pre-patent period was observed ( vaccine group median 8.5 days [ range 7.5–9 ] , control group median 9 days [ range 7–9 ] ) . Conclusions Despite the first observation in human experimental malaria infection of a significant association between vaccine-induced in vitro growth inhibitory activity and in vivo parasite multiplication rate , this did not translate into any observable clinical ly relevant vaccine effect in this small group of volunteers . Trial Registration Clinical Trials.gov [ NCT00984763 Background : Quadrivalent meningococcal polysaccharide conjugate vaccine ( MCV4 ) is routinely recommended for healthy youth in the United States , but there are no data about its use in HIV-infected people . Methods : P1065 is a Phase I/II trial of MCV4 safety and immunogenicity in HIV-infected children and youth performed at 27 US sites of the IMPAACT network . All youth ( 11–24 years old ) received 1 dose of open-label MCV4 at entry . St and ardized question naires were used to evaluate safety . Baseline protective immunity was defined as rabbit serum bactericidal antibody ( rSBA ) titer ≥1:128 . Immunogenic response was defined as a ≥4-fold rise in rSBA against each meningococcal serogroup . Multivariable logistic regression analysis was used to evaluate the association of demographic and clinical characteristics on immunogenic response to serogroup C. Results : Among 319 subjects who received MCV4 , 10 ( 3.1 % ) reported immediate adverse events which were local and mild , and 7 ( 2.2 % ) experienced Grade ≥3 adverse events , unrelated to vaccine . The 305 subjects with serologic data had a median age of 17 years and were 59 % male , 50 % Black , and 38 % Latino . Subjects were stratified by entry CD4 % : 12 % , CD4 < 15 % ; 40 % , 15 % to 24 % ; and 48 % , ≥25 % . Baseline protective immunity varied by serogroup : A , 41 % ; C , 11 % ; W-135 , 15 % ; Y , 35 % The immunogenic response rates to serogroups A , C , W-135 , and Y were 68 % , 52 % , 73 % , and 63 % , respectively . In multivariable logistic regression models , lower entry CD4 % , higher entry viral load , and CDC Class B/C diagnosis were associated with significantly lower odds of response to serogroup C. Conclusion : Many HIV-infected youth naturally acquire meningococcal immunity . MCV4 is safe and immunogenic in HIV-infected youth , but response rates are lower than in healthy youth , particularly for those with more advanced HIV clinical , immunologic , and virologic status Background Ad35.CS.01 is a pre-erythrocytic malaria c and i date vaccine . It is a codon optimized nucleotide sequence representing the P. falciparum circumsporozoite ( CS ) surface antigen inserted in a replication deficient Adenovirus 35 backbone . A Phase 1a trial has been conducted in the USA in naïve adults and showed that the vaccine was safe . The aim of this study is to assess the safety and immunogenicity of ascending dosages in sub Saharan Africa . Methods A double blind , r and omized , controlled , dose escalation , phase Ib trial was conducted in a rural area of Balonghin , the Saponé health district ( Burkina Faso ) . Forty-eight healthy adults aged 18 - 45 years were r and omized into 4 cohorts of 12 to receive three vaccine doses ( day 0 , 28 and 84 ) of 109 , 1010 , 5X1010 , 1011 vp of Ad35.CS.01 or normal saline by intra muscular injection . Subjects were monitored carefully during the 14 days following each vaccination for non serious adverse events . Severe and serious adverse events were collected throughout the participant study duration ( 12 months from the first vaccination ) . Humoral and cellular immune responses were measured on study days 0 , 28 , 56 , 84 , 112 and 140 . Results Of the forty-eight subjects enrolled , forty-four ( 91.7 % ) received all three scheduled vaccine doses . Local reactions , all of mild severity , occurred in thirteen ( 27.1 % ) subjects . Severe ( grade 3 ) laboratory abnormalities occurred in five ( 10.4 % ) subjects . One serious adverse event was reported and attributed to infection judged unrelated to vaccine . The vaccine induced both antibody titers and CD8 T cells producing IFNγ and TNFα with specificity to CS while eliciting modest neutralizing antibody responses against Ad35 . Conclusion Study vaccine Ad35.CS.01 at four different dose levels was well-tolerated and modestly immunogenic in this population . These results suggest that Ad35.CS.01 should be further investigated for preliminary efficacy in human challenge models and as part of heterologous prime-boost vaccination strategies . Trial Registration Clinical Trials.gov NCT01018459 http:// clinical Highlights • MVA.HIVA vaccine was tested for the first time in HIV-1-exposed infants in Africa.• PedVacc 002 had 99 % retention of infants over 48 weeks of follow-up.• MVA.HIVA was safe , but not sufficiently immunogenic.• MVA.HVA did not interfere with routine childhood vaccines except for induction of HBV antibodies.• MVA is well suited as a vaccine vector for infants under 1 year of age Four serotypes of monovalent live attenuated dengue virus vaccine c and i date s were tested for reactogenicity and immunogenicity in 49 flavivirus non-immune adult human volunteers . The four monovalent c and i date s were then combined into a tetravalent formulation and given to another 10 volunteers Output:	However , neutropenia was generally transient and had a benign clinical outcome , after vaccination with either multiple novel c and i date s or well-known licensed vaccines . Additionally , the vaccine recipients with neutropenia frequently had lower baseline ANC than non-neutropenic vaccinees .
MS2903	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background : We conducted a prospect i ve trial r and omizing 75 physicians to either a control or intervention arm to evaluate the impact of providing patient-reported information on anxiety and other mental health symptoms and disorders to primary care physicians . Methods : Five hundred seventy-three patients of the study physicians who met entry criteria were r and omized to either usual care or usual care supplemented with feedback of patient-reported mental health information to physicians . This mental health information was derived from initial patient-reported question naires completed in waiting rooms of physicians contracted to a mixed-model health maintenance organization in Colorado . Main outcome measures included impact of intervention on rates of ( 1 ) chart notation of anxiety , depression , or other mental health diagnoses or symptoms ; ( 2 ) referral to mental health specialists ; ( 3 ) prescription of psychotropic medications ; ( 4 ) hospitalization ; and ( 5 ) office visits during a 5-month observation period . Results : Physicians receiving feedback on previously unrecognized and untreated anxiety patients were more likely to make chart notations ( adjusted odds ratio [ AOR ] = 2.51 , 95 percent confidence interval [ CI ] = 1.62 - 3.87 ) , to make referrals to mental health specialists ( AOR = 3.86 , 95 percent CI = 1.63 - 9.16 ) , and to see patients for more frequent outpatient visits ( AOR = 1.73 , 95 percent CI = 1.11 - 2.70 ) . Use of psychotropic medications and rate of hospitalizations did not differ significantly . Conclusions : Providing patient-reported mental health information to primary care physicians result ed in increased recognition and referral rates for previously unrecognized and untreated anxiety patients , plus an increase in primary care visits , without concomitant increases in the use of psychotropic medications or rate of hospitalizations Background Only approximately half of patients with hypertension have their blood pressure controlled , due in large part to the tendency of primary care providers ( PCPs ) not to intensify treatment when blood pressure values are elevated . Objective This study tested the effect of an intervention design ed to help patients ask questions at the point of care to encourage PCPs to appropriately intensify blood pressure treatment . Methods PCPs and their patients with hypertension ( N=500 ) were recruited by letter and r and omized into 2 study groups : ( 1 ) intervention condition in which patients used a fully automated website each month to receive tailored messages suggesting questions to ask their PCP to improve blood pressure control , and ( 2 ) control condition in which a similar tool suggested questions to ask about preventive services ( eg , cancer screening ) . The Web-based tool was design ed to be used during each of the 12 study months and before scheduled visits with PCPs . The primary outcome was the percentage of patients in both conditions with controlled blood pressure . Results Of 500 enrolled patients ( intervention condition : n=282 ; control condition : n=218 ) , 418 ( 83.6 % ) completed the 12-month follow-up visit . At baseline , 289 ( 61.5 % ) of participants had controlled blood pressure . Most ( 411/500 , 82.2 % ) participants used the intervention during at least 6 of 12 months and 222 ( 62.5 % ) reported asking questions directly from the Web-based tool . There were no group differences in asking about medication intensification and there were no differences in blood pressure control after 12 months between the intervention condition ( 201/282 , 71.3 % ) and control condition ( 143/218 , 65.6 % ; P=.27 ) groups . More intervention condition participants discussed having a creatinine test ( 92 , 52.6 % vs 49 , 35.5 % ; P=.02 ) and urine protein test ( 81 , 44.8 % vs 21 , 14.6 % ; P<.001 ) , but no group differences were observed in the rate of testing . The control condition participants reported more frequent discussion s about tetanus and pneumonia vaccines and reported more tetanus ( 30 , 13.8 % vs 15 , 5.3 % ; P=.02 ) and pneumonia ( 25 , 11.5 % vs 16 , 5.7 % ; P=.02 ) vaccinations after 12 months . Conclusions The use of an interactive website design ed to overcome clinical inertia for hypertension care did not lead to improvements in blood pressure control . Participant adherence to the intervention was high . The control intervention led to positive changes in the use of preventive services ( eg , tetanus immunization ) and the intervention condition led to more discussion s of hypertension-relevant tests ( eg , serum creatinine and urine protein ) . By providing patients with individually tailored questions to ask during PCP visits , this study demonstrated that participants were likely to discuss the questions with PCPs . These discussion s did not , however , lead to improvements in blood pressure control . Trial Registration Clinical Trials.gov NCT00377208 ; http:// clinical trials.gov/ct2/show/NCT00377208 ( Archived by WebCite at http://www.webcitation.org/6IqWiPLon ) The aim of the review was to assess the effect of patient education in ischaemic heart disease . Thirteen r and omised controlled trials of moderate to good quality including 68,556 patients were selected . The effect on mortality , cardiac morbidity , hospitalisation and health-related quality of life was assessed and only non-significant tendencies of effect were found . The authors of the review nevertheless conclude that the review supports current rehabilitation programmes that include patient education . Further research in patient education , especially concerning the most effective methods of education delivery , is needed BACKGROUND To compare three approaches for improving compliance with breast cancer screening in older women . METHODS R and omized controlled trial using three parallel group practice s at a public hospital . Subjects included women aged 65 years and older ( n = 803 ) who were seen by residents ( n = 66 ) attending the ambulatory clinic from October 1 , 1989 , through March 31 , 1990 . All provider groups received intensive education in breast cancer screening . The control group received no further intervention . Staff in the second group offered education to patients at their visit . In addition , flowsheets were used in the " Prevention Team " group and staff had their tasks redefined to facilitate compliance . RESULTS Medical records were review ed to determine documented offering/receipt of clinical breast examination and mammography . A subgroup of women without previous clinical breast examination ( n = 540 ) and without previous mammography ( n = 471 ) were analyzed to determine the effect of the intervention . During the intervention period , women without a previous clinical breast examination were offered an examination significantly more often in the Prevention Team group than in the control group , adjusting for age , race , and comorbidity and for physicians ' gender and training level . The patients in the Prevention Team group were offered clinical breast examination ( 31.5 % ) more frequently than those in the patient education or control groups , but this was not significant after adjusting for the above covariates . Likewise , mammography was offered more frequently to patients in the Prevention Team and in the patient education group than to patients in the control group , after adjusting for the factors above using logistic regression . CONCLUSIONS The results provide support for patient education and organizational changes that involve nonphysician personnel to enhance breast cancer screening among older women , particularly those without previous screening CONTEXT For patients with cancer-related pain and their physicians , routine oncology visits are an opportunity to adjust the analgesic regimen and secure better pain control . However , treatment intensification occurs haphazardly in practice . OBJECTIVES To estimate the effect of patient-centered tailored education and coaching ( TEC ) on the likelihood of analgesic treatment adjustment during oncology visits , and in turn , the influence of treatment adjustment on subsequent cancer pain control , we studied patients enrolled in a r and omized trial of TEC . METHODS Just before a scheduled oncology visit , 258 patients with at least moderate baseline pain received TEC or control ; just after the same visit , they reported on whether the physician recommended a new pain medicine or a change in dose of an existing medicine . Pain severity and pain-related impairment were measured two , six , and 12 weeks later . RESULTS Patients assigned to TEC were more likely than controls to report a change in the analgesic treatment regimen ( 60 % vs. 36 % , P<0.01 ) ; significant effects persisted after adjustment for baseline pain , study site , and physician ( adjusted odds ratio 2.61 , 95 % confidence interval 1.55 , 4.40 , P<0.01 ) . In a mixed-effects repeated measures regression , analgesic change ( but not TEC itself ) was associated with a sustained decrease in pain severity ( P<0.05 ) . CONCLUSION TEC increases the likelihood of self-reported , physician-directed adjustments in analgesic prescribing , and treatment intensification is associated with better cancer pain outcomes Introduction This study evaluated the impact of a waiting room-administered , low-literacy , computer multimedia diabetes education program on patient self-management and provider intensification of therapy . Methods In this r and omized , controlled trial , 129 participants either viewed a computer multimedia education program ( intervention group ) or read an educational brochure ( control group ) while in the waiting room . Participants were uninsured , primarily ethnic minority adults with type 2 diabetes receiving care from a county clinic in Chicago , Illinois . Wilcoxon test , t-test , and linear mixed model analyses evaluated changes in diabetes knowledge , self-efficacy , behaviors , medications prescribed , hemoglobin A1c ( HbA1c ) , and blood pressure levels over 3 months . Results During the study period , there was an increase in the number of oral diabetes medications prescribed over three months to multimedia users compared with those in the control group ( P=0.017 ) . HbA1c declined by 1.5 in the multimedia group versus 0.8 in the control group ( P=0.06 ) . There were no differences between groups in changes in blood pressure levels , self-efficacy , and most diabetes-related behaviors . Self-reported exercise increased in the control group compared with the multimedia group ( 0.9 days/week vs. 0.1 days/week , P=0.016 ) . Conclusion Multimedia users received a greater intensification of diabetes therapy , but demonstrated no difference in self-management in comparison with those receiving educational brochures . The availability of a computer multimedia program in the waiting room appears to be a novel and acceptable approach in providing diabetes education for underserved population BACKGROUND Hypertension is generally poorly controlled in primary care . One possible intervention for improving control is the harnessing of patient expertise through education and encouragement to challenge their care . AIM To determine whether encouraging patients to manage their hypertension in an ' expert ' manner , by providing them with information in a clear clinical guideline , coupled with an explicit exhortation to become involved in and to challenge their own care if appropriate , would improve their care . DESIGN OF STUDY Single blind r and omised controlled trial of detailed guideline versus st and ard information . SETTING Single urban general practice over 1 year . METHOD Patient-held guideline with written explicit exhortation to challenge care when appropriate . Two hundred and ninety-four of 536 eligible patients on the practice hypertension register were recruited , all of whom were r and omised into one of two groups . Two hundred and thirty-six patients completed the study . RESULTS PRIMARY OUTCOME average systolic blood pressure . SECONDARY OUTCOMES proportion of patients with blood pressure < 150 mmHg systolic and < 90 mmHg diastolic , average cholesterol , proportion of patients prescribed statins and aspirin according to guideline , hospital anxiety and depression score . No clinical ly , or statistically significant differences were found between intervention and control with respect to all parameters or in anxiety and depression levels . Statin and aspirin use improved throughout the course of the study in both groups . Statin use showed a trend ( P = 0.02 ) in favour of control . CONCLUSION In this study there was no clinical ly significant perceived benefit to patients as a result of providing them with a hypertension guideline . Patient guidelines are currently planned for many chronic illnesses . It is important to determine the utility of such interventions before scarce re sources are applied to them Background : Too few patients with nonvalvular atrial fibrillation ( NVAF ) receive appropriate antithrombotic therapy . We tested the short-term ( primary outcome ) and long-term ( secondary outcome ) effect of a patient decision aid on the appropriateness of antithrombotic therapy among patients with NVAF . Methods : We conducted a cluster r and omized trial with blinded outcome assessment involving 434 NVAF patients from 102 community-based primary care practice s. Patients in the intervention group received a self-administered booklet and audiotape decision aid tailored to their personal stroke risk profile . Patients in the control group received usual care . The primary outcome measure was change in antithrombotic therapy at 3 months . Appropriateness of therapy was defined using the American College of Chest Physicians ( ACCP ) recommendations . Results : The mean patient age was 72 years , and the median duration of NVAF was 5 years . In the control group , there was a 3 % decrease over 3 months in the number of patients receiving therapy appropriate to their risk of stroke ( 40 % [ 85/215 ] at baseline v. 37 % [ 79/215 ] at 3 months ) . In the intervention group , the number of patients receiving therapy appropriate to their stroke risk increased by 9 % ( 32 % [ 69/219 ] at baseline v. 41 % [ 89/219 ] at 3 months ) . Although the proportion of patients whose therapy met the ACCP treatment recommendations did not differ between study arms at baseline ( p = 0.11 ) or 3 months ( Output:	We found that patient-reported health information interventions and patient education interventions probably improve healthcare professionals ' adherence to recommended clinical practice ( moderate certainty evidence ) . We also found that patient information interventions may improve healthcare professionals ' adherence to recommended clinical practice ( low certainty evidence ) . Patient decision aids may make little or no difference to the number of healthcare professionals ' adhering to recommended clinical practice ( low-certainty evidence ) . Our findings strengthen the belief that patient-mediated interventions have the potential to improve professional practice , especially patient-reported health information interventions and patient education interventions . PRACTICE IMPLICATION S Our findings show that patient-reported health information interventions and patient education interventions are relevant approaches to improve professional practice . Thus , it seems reasonable to conclude that these types of patient-mediated interventions can contribute to improving the quality of healthcare services
MS2904	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Flavonoids are bioactive compounds found in foods such as tea , chocolate , red wine , fruit , and vegetables . Higher intakes of specific flavonoids and flavonoid-rich foods have been linked to reduced mortality from specific vascular diseases and cancers . However , the importance of flavonoids in preventing all-cause mortality remains uncertain . OBJECTIVE The objective was to explore the association between flavonoid intake and risk of 5-y mortality from all causes by using 2 comprehensive food composition data bases to assess flavonoid intake . DESIGN The study population included 1063 r and omly selected women aged > 75 y. All-cause , cancer , and cardiovascular mortalities were assessed over 5 y of follow-up through the Western Australia Data Linkage System . Two estimates of flavonoid intake ( total flavonoidUSDA and total flavonoidPE ) were determined by using food composition data from the USDA and the Phenol-Explorer ( PE ) data bases , respectively . RESULTS During the 5-y follow-up period , 129 ( 12 % ) deaths were documented . Participants with high total flavonoid intake were at lower risk [ multivariate-adjusted HR ( 95 % CI ) ] of 5-y all-cause mortality than those with low total flavonoid consumption [ total flavonoidUSDA : 0.37 ( 0.22 , 0.58 ) ; total flavonoidPE : 0.36 ( 0.22 , 0.60 ) ] . Similar beneficial relations were observed for both cardiovascular disease mortality [ total flavonoidUSDA : 0.34 ( 0.17 , 0.69 ) ; flavonoidPE : 0.32 ( 0.16 , 0.61 ) ] and cancer mortality [ total flavonoidUSDA : 0.25 ( 0.10 , 0.62 ) ; flavonoidPE : 0.26 ( 0.11 , 0.62 ) ] . CONCLUSIONS Using the most comprehensive flavonoid data bases , we provide evidence that high consumption of flavonoids is associated with reduced risk of mortality in older women . The benefits of flavonoids may extend to the etiology of cancer and cardiovascular disease Flavonols , flavanones and flavones ( FLAV ) are sub-classes of flavonoids that exert cardioprotective and anti-carcinogenic properties in vitro and in vivo . We aim ed to estimate the FLAV dietary intake , their food sources and associated lifestyle factors in ten European countries participating in the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) study . FLAV intake and their food sources for 36 037 subjects , aged between 35 and 74 years , in twenty-seven study centres were obtained using st and ardised 24 h dietary recall software ( EPIC-SOFT ) . An ad hoc food composition data base on FLAV was compiled using data from US Department of Agriculture and Phenol-Explorer data bases and was exp and ed using recipes , estimations and flavonoid retention factors in order to increase its correspondence with the 24 h dietary recall . Our results showed that the highest FLAV-consuming centre was the UK health-conscious group , with 130·9 and 97·0 mg/d for men and women , respectively . The lowest FLAV intakes were 36·8 mg/d in men from Umeå and 37·2 mg/d in women from Malmö ( Sweden ) . The flavanone sub-class was the main contributor to the total FLAV intake ranging from 46·6 to 52·9 % depending on the region . Flavonols ranged from 38·5 to 47·3 % and flavones from 5·8 to 8·6 % . FLAV intake was higher in women , non-smokers , increased with level of education and physical activity . The major food sources were citrus fruits and citrus-based juices ( especially for flavanones ) , tea , wine , other fruits and some vegetables . We concluded that the present study shows heterogeneity in intake of these three sub-classes of flavonoids across European regions and highlights differences by sex and other sociodemographic and lifestyle factors BACKGROUND The association of the polyphenol content of human diet with pulmonary function is not yet fully understood . This study aims at evaluating the association of polyphenol consumption with lung function in a novel holistic approach . METHODS A cross-sectional analysis of 4551 women and 5108 men ( age ≥35 years ) from the Moli-sani study was performed . Participants were r and omly recruited from the general population . The EPIC-FFQ was used for the dietary assessment . Polyphenol intakes were calculated using Eurofir-eBASIS , and a polyphenol antioxidant content ( PAC ) score was constructed to assess the total content of the diet in these nutrients . Pulmonary function maneuvers were performed , and the forced vital capacity ( FVC ) and forced expiratory volume in the first second ( FEV1 ) were measured ; FVC% predicted and FEV1 % predicted were computed using the European Community of Coal and Steel prediction equations that included height and age . RESULTS In both genders , in age , height , and energy intake adjusted models , the majority of classes of polyphenols ( mg/day ) showed a positive association with FEV1 , FVC , FEV1 % predicted , and FVC% predicted ( β-coef > 0 , P < .05 ) . Associations remained significant after adjustment for confounding factors in most cases ( β-coef > 0 , P < .05 ) . The PAC score was associated in both genders with an increase in pulmonary function parameters ( β-coef > 0 , P < .05 ) . The inclusion of white blood cell ( WBC ) counts in the multivariate model reduced the association in men but not in women . . CONCLUSIONS A higher overall polyphenol content of human diet was associated with better pulmonary function in a general population . The association might be partially mediated by WBC in men OBJECTIVES The effect of the polyphenol content of the human diet on mortality risk is not yet fully understood . The aim of this study was to evaluate the association of a polyphenol-rich diet with mortality rate and a possible mediation effect by inflammation , in what we believe to be a novel , holistic approach . METHODS We analyzed 21 302 participants ( 10 980 women and 10 322 men , aged ≥35 y ) from the Moli-sani cohort . The participants were followed up for a median of 8.3 y. The European Prospect i ve Investigation into Cancer and Nutrition food frequency question naire ( FFQ ) was used for dietary assessment . Flavonol , flavone , flavanone , flavanol , anthocyanin , isoflavone , and lignan intakes were calculated using European Food Information Re source -Bioactive Substances in Food Information Systems and the polyphenol antioxidant content (PAC)-score was constructed to assess the total content of these nutrients in the diet . RESULTS Participants included in the highest quintile of intake of various polyphenol classes and subclasses presented a significant lower all-cause mortality risk compared with those in the lowest group of consumption ( hazard ratio [ HR ] < 1 ; P < 0.05 ) . Cox regression analyses adjusted for potential confounders indicated that participants in higher quintiles of PAC-score had lower all-cause mortality risk ( HR < 1 ; P < 0.05 ) . When cause-specific mortality rates were considered , similar effects were observed for cardiocerebrovascular and cancer mortality ( HR < 1 ; P < 0.05 ) . CONCLUSIONS The polyphenol content of the diet was associated with reduced mortality risk in a Mediterranean population , possibly through an antiinflammatory mechanism BACKGROUND Flavonoids are plant-based phytochemicals with cardiovascular protective properties . Few studies have comprehensively examined flavonoid classes in relation to cardiovascular disease mortality . OBJECTIVE We examined the association between flavonoid intake and cardiovascular disease ( CVD ) mortality among participants in a large , prospect i ve US cohort . DESIGN In 1999 , a total of 38,180 men and 60,289 women in the Cancer Prevention Study II Nutrition Cohort with a mean age of 70 and 69 y , respectively , completed question naires on medical history and lifestyle behaviors , including a 152-item food-frequency question naire . Cox proportional hazards modeling was used to calculate multivariate-adjusted hazard RRs and 95 % CIs for associations between total flavonoids , 7 flavonoid classes , and CVD mortality . RESULTS During 7 y of follow-up , 1589 CVD deaths in men and 1182 CVD deaths in women occurred . Men and women with total flavonoid intakes in the top ( compared with the bottom ) quintile had a lower risk of fatal CVD ( RR : 0.82 ; 95 % CI : 0.73 , 0.92 ; P-trend = 0.01 ) . Five flavonoid classes-anthocyanidins , flavan-3-ols , flavones , flavonols , and proanthocyanidins-were individually associated with lower risk of fatal CVD ( all P-trend < 0.05 ) . In men , total flavonoid intakes were more strongly associated with stroke mortality ( RR : 0.63 ; 95 % CI : 0.44 , 0.89 ; P-trend = 0.04 ) than with ischemic heart disease ( RR : 0.90 ; 95 % CI : 0.72 , 1.13 ) . Many associations appeared to be nonlinear , with lower risk at intakes above the referent category . CONCLUSIONS Flavonoid consumption was associated with lower risk of death from CVD . Most inverse associations appeared with intermediate intakes , suggesting that even relatively small amounts of flavonoid-rich foods may be beneficial Background : Flavonoids exert anti-inflammatory properties and modulate oxidative stress in vitro , suggesting a protective effect on lung function , but epidemiological studies examining this association are scarce . Methods : A stratified r and om sample was drawn from the GA2LEN screening survey , in which 55,000 adults aged 15 to 75 answered a question naire on respiratory symptoms . Post-bronchodilator spirometry was obtained from 2850 subjects . Forced vital capacity ( FVC ) , the ratio between the forced exhaled volume in 1 second ( FEV1 ) and FVC ( FEV1/FVC ) , FVC below lower limit of normal ( FVC < LLN ) , and FEV1/FVC < LLN were calculated . Intake of the six main subclasses of flavonoids was estimated using the GA2LEN Food Frequency Question naire . Adjusted associations between outcomes and each subclass of flavonoids were examined with multivariate regressions . Simes ’ procedure was used to test for multiple comparisons . Results : A total of 2599 subjects had valid lung function and dietary data . A lower prevalence of FVC < LLN ( airway restriction ) was observed in those with higher total flavonoid ( adjusted odds ratio ( aOR ) , higher vs. lowest quintile intake 0.58 ; 95 % Confidence Interval ( CI ) 0.36 , 0.94 ) , and pro-anthocyanidin intakes ( aOR 0.47 ; 95 % CI 0.27 , 0.81 ) . A higher FEV1/FVC was associated with higher intakes of total flavonoids and pro-anthocyanidins ( adjusted correlation coefficient ( a β-coeff 0.33 ; 0.10 , 0.57 and a β-coeff 0.44 ; 95 % CI 0.19 , 0.69 , respectively ) . After Simes ’ procedure , the statistical significance of each of these associations was attenuated but remained below 0.05 , with the exception of total flavonoids and airway restriction . Conclusions : This population -based study in European adults provides cross-sectional evidence of a positive association of total flavonoid intake and pro-anthocyanidins and ventilatory function , and a negative association with spirometric restriction in European adults Background / Objectives : The objective of this study is to extract and assess data on the dietary intake of flavonoids and lignans in a healthy free-living Mediterranean population , using newly up date d harmonized European Union food composition data . This work also aim ed at analyzing in a holistic way the total content of the diet in major classes of polyphenols . Subjects/ Methods : Six thous and nine hundred and eighty-one men and 7048 women ( aged ⩾35years ) of the Moli-sani cohort , r and omly recruited from the general population , were analyzed . The European Prospect i ve Investigation into Cancer ( EPIC ) and Nutrition-Food Frequency Question naire was used for dietary assessment . The polyphenol content of each food group was evaluated using Eurofir BioActive Substances in Food Information System and the United States Department of Agriculture food composition tables ( FCTs ) , when data were missing . Flavonol , flavone , flavanone , flavanol , anthocyanin , isoflavone and lignan intakes were calculated and polyphenol antioxidant content ( PAC ) score ( −28 , 28 ) constructed , to assess the total content of the diet in these nutrients . Results : Seasonal and citrus fruits , leafy , grain , pod and root vegetables , and onions and garlic accounted for different proportions ( 11–70 % ) of the total intake of different polyphenols . Within the Moli-sani population , men or older , Output:	Total flavonoids and specific subclasses , but not total polyphenols , have been apparently associated with a low risk of diabetes , cardiovascular events and all-cause mortality .
MS2905	*TASK* the task is to summarize an input biomedical literature in six sentences *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 analyze sources search ed in Cochrane review s , to determine the proportion of trials included in review s that are indexed in major data bases , and to compare the quality of these trials with those from other sources . METHODS All new systematic review s in the Cochrane Library , Issue1 2001 , that were restricted to r and omized controlled trials ( RCTs ) or quasi- RCTs were selected . The sources search ed in the review s were recorded , and the trials included were checked to see whether they were indexed in four major data bases . Trials not indexed were checked to determine how they could be identified . The quality of trials found in major data bases was compared with those found from other sources . RESULTS The range in the number of data bases search ed per review ranged between one and twenty-seven . The proportion of the trials in the four data bases were Cochrane Controlled Trials Register = 78.5 % , MEDLINE = 68.8 % , Embase = 65.0 % , and Science/Social Sciences Citation Index = 60.7 % . Search ing another twenty-six data bases after Cochrane Controlled Trials Register ( CCTR ) , MEDLINE , and Embase only found 2.4 % additional trials . There was no significant difference between trials found in the CCTR , MEDLINE , and Embase compared with other trials , with respect to adequate allocation concealment or sample size . CONCLUSIONS There was a large variation between review s in the exhaustiveness of the literature search es . CCTR was the single best source of RCTs . Additional data base search ing retrieved only a small percentage of extra trials . Contacting authors and manufacturers to find unpublished trials appeared to be a more effective method of obtaining the additional better quality trials BACKGROUND / AIMS Cefotaxime or ceftriaxone were considered the first-choice antibiotic for empirical treatment in cirrhotic patients developing spontaneous bacterial peritonitis . It has been suggested that ciprofloxacin could be an alternative to cefotaxime or ceftriaxone in cirrhotic patients developing spontaneous bacterial peritonitis . The aim of the present study was to compare oral ciprofloxacin with cefotaxime and ceftriaxone in the treatment of spontaneous bacterial peritonitis in cirrhotic patients . METHODOLOGY Fifty-three hospitalized cirrhotic patients with spontaneous bacterial peritonitis were prospect ively included and r and omized into three groups : group A ( n = 16 ) ; received orally 500 mg ciprofloxacin every 12 h , group B ( n = 18 ) ; received intravenous cefotaxime 2 g every 8 h and group C ( n = 19 ) received intravenous ceftriaxone 2 g every 24 h. RESULTS 15 patients from the ciprofloxacin group , 17 from the cefotaxime group and 17 patients from the ceftriaxone group were finally analyzed . Spontaneous bacterial peritonitis resolution in three groups was found to be 80 % , 76 % , and 83 % , respectively ( p = NS ) . Incidence of complications and hospital mortality was similar in the three groups . No adverse events were observed in any of the three groups . The cost of the treatment was statistically lower in the ciprofloxacin group than in the cefotaxime group and ceftriaxone group ( p < 0.001 ) . CONCLUSIONS These results suggest that orally ciprofloxacin is as effective as cefotaxime and ceftriaxone in the empirical treatment of spontaneous bacterial peritonitis in cirrhotic patients , and is also less expensive and can be administered orally We compared the effectiveness and incidence of nephrotoxicity of ampicillin-tobramycin and cefotaxime in 73 cirrhotics who had severe bacterial infection . Most of these patients had spontaneous peritonitis and /or bacteremia . Patients were r and omly allocated into two groups . Group I included 36 patients treated with ampicillin-tobramycin and Group II comprised 37 patients treated with cefotaxime . Patients from both groups were similar with respect to clinical data , st and ard liver and renal function tests , types of infection and isolated organisms . Ninety-two per cent of bacteria isolated in Group I and 98 % of those isolated in Group II were susceptible in vitro to ampicillin-tobramycin and to cefotaxime , respectively . Ampicillin-tobramycin cured the infection in 56 % of Group I patients , and cefotaxime in 85 % of Group II patients ( p less than 0.02 ) . Five patients treated with ampicillin-tobramycin , and none treated with cefotaxime developed superinfections ( p = 0.024 ) . Nephrotoxicity ( impairment of renal function associated with an increase of urinary beta 2-microglobulin to over 2,000 micrograms per liter ) occurred in two patients in Group I and none in Group II . These results suggest that broad-spectrum cephalosporins should be considered as first choice antibiotics in cirrhotic patients with severe infections BACKGROUND AND AIM Spontaneous bacterial peritonitis and bacterascites prevalence in asymptomatic cirrhotic patients on large-volume paracentesis is unknown . The aim of this study was to investigate spontaneous bacterial peritonitis and bacterascites prevalence in a prospect i ve cohort of cirrhotic out patients following large-volume paracentesis with low risk of infection . METHODS We prospect ively studied all large-volume paracenteses performed in cirrhotic out patients for 1 year . Patients with fever , abdominal pain , peritonism or hepatic encephalopathy were excluded from the study . The ascitic fluid was analyzed by means of a reagent strip with a colorimetric scale from 0 to 4 . A strip test of 0 or 1 was considered negative . In those cases with a reagent strip > or = 2 , conventional polymorphonuclear count was performed . Ascitic fluid culture was done into blood culture bottles in all cases . RESULTS We performed 204 paracenteses in 40 patients . Nine cases were excluded . Culture-negative neutrocytic ascites was diagnosed in one case ( 0.5 % ) , while bacterascites was diagnosed in six out of 195 cases ( 3 % ) , mainly by gram-positive cocci . CONCLUSION The spontaneous bacterial peritonitis prevalence in outpatient cirrhotics with low risk of infection undergoing large-volume paracentesis is very low . Moreover , the prevalence of bacterascites is low and without clinical consequences . The routine analysis of ascitic fluid may be unnecessary in this clinical setting . Nevertheless , the use of reagent strips is a reasonable alternative due to its accessibility and low cost We compared cefonicid ( 2 g every 12 h ) and ceftriaxone ( 2 g every 24 h ) for their efficacy and safety in treating spontaneous bacterial peritonitis in cirrhotic patients in an open r and omized clinical trial ( 30 patients in each group ) . Clinical , laboratory , and bacteriologic characteristics were similar in both groups . Ceftriaxone-susceptible strains were isolated on 44 occasions ( 94 % ) , and cefonicid-susceptible strains were isolated on 43 occasions ( 91.5 % ) . The antibiotic concentration in ascitic fluid/MIC ratio for ceftriaxone was > 100 throughout the dose interval ( 24 h ) , while it was lower for cefonicid ( between 1 and 18 ) . A total of 100 % of patients treated with ceftriaxone , and 94 % of those treated with cefonicid were cured of their infections ( P was not significant ) . Hospitalization mortality was 37 % in the cefonicid group and 30 % in the ceftriaxone group ( P was not significant ) . The time that elapsed between the initiation of treatment and the patient 's death was shorter in the cefonicid group patients ( 5.3 + /- 3.90 days ) than in the ceftriaxone group patients ( 11.8 + /- 9.15 days ) ( P < 0.05 ) . None of the patients presented with superinfections , and only two patients treated with cefonicid and three patients treated with ceftriaxone developed colonizations with Enterococcus faecalis or C and ida albicans . Ceftriaxone and cefonicid are safe and useful agents for treating cirrhotic spontaneous bacterial peritonitis , although the pharmacokinetic characteristics of ceftriaxone seem to be more advantageous than those of cefonicid UNLABELLED Recent studies have shown that the diagnosis of spontaneous bacterial peritonitis ( SBP ) can be rapidly obtained using leukocyte esterase reagent strips . However , published studies were restricted to one or two centers , and the number of patients with SBP was thus limited . The aims of the current prospect i ve multicenter study were : ( 1 ) to assess the diagnostic accuracy of the Multistix 8SG urine test for the diagnosis of SBP ; and ( 2 ) to assess the prevalence of SBP . From January to May 2004 , 2 reactive strips were tested independently in in patients with cirrhosis and in out patients undergoing paracentesis . Cultures of ascitic fluid were performed at the bedside using aerobic and anaerobic blood culture bottles . Two thous and one hundred twenty-three paracenteses were performed in 1,041 patients from 70 centers . One hundred seventeen sample s , obtained from 91 patients , had ascites polymorphonuclear cell ( PMN ) counts > or=250/microl ( range , 250 - 34,000 ) , among which 56 were associated with positive ascitic fluid cultures . The prevalence of SBP was 5.5 % in the whole population , 9 % in in patients , and 1.3 % in out patients ( P<0.0001 ) . The prevalence of SBP was 0.57 % in asymptomatic out patients versus 2.4 % in symptomatic out patients ( P=0.04 ) . Using a threshold of 2 + for positivity of the reagent strip , sensitivity was 45.3 % for the diagnosis of SBP , specificity was 99.2 % , positive predictive value was 77.9 % , and negative predictive value was 96.9 % . CONCLUSION This study confirms the low prevalence of SBP in asymptomatic out patients according to a priori defined criteria , and indicates an absence of diagnostic efficacy for this specific strip test Royal Free Hospital , London , UK Introduction Background of the European Liver Transplant RegistrySince 1968 the European Liver Transplant Registry ( ELTR ) collects prospect ively the data of liver transplantation ( LT ) in 145 centersall over Europe . It represents more than 95 % of the overallEuropean data compared to the published ofﬁcial ﬁgures [ 1 ] . This collection ismade prospect ivelythroughast and ardized question -naire . The ﬁrst part of the question naire includes items regarding date and indicationfor LT , donor and recipient data , surgical tech-niqueofLT , and theimmediatepostoperativeimmunosuppressiontherapy . The second part concerns graft and patient outcome , and immunosuppressive regimen follow-up . Participation in the ELTRis voluntary and a st and ard computerized data base is provided tocontributing centers with detailed instructions for the collection of accurate and uniform information [2].Along with reports concerning LT for speciﬁc hepatic diseases[3–12],ELTRhasallowedthedevelopmentofriskmodelsforliver-transplantation mortality according to the characteristics of thedonor and recipient , and of the transplant procedure [ 13,14 ] . Quality ofthe data isassessedroutinely . Aregularauditingpro-cessisconductedeachyeartoensurethereliabilityofthescientiﬁc analysis of the data , a control of the good adequacy between ELTR question naire and patient charts is performed by r and omly con-ductedauditvisits . Results oftheseauditvisitshaveindicatedthatELTR data were reliable and the scientiﬁc results of ELTR can beconsidered credible and representative of LT in Europe [15–18].In addition , a control quality program has been developed inter-nally . The data are subjected to checks for completeness , consis-tency , and range . Comprehensive logical intra- and inter-up date sare performed . Moreover , the ELTR has established agreementswith the European Organ Sharing Organizations ( OSO ) : UnitedKingdom Transplant Service Support Authority (UKTransplant),Spanish Organizacion Nacional de Transplantes ( ONT ) , Sc and ina-vian Sc and itransplant ( SKT ) , Dutch Transplant Foundation (NTS),Eurotransplant ( ET ) , French Agence de la Biomedecine ( ABM ) toexchange data collectedfromEuropeanCenters and tocrosscheckcommon data between OSO and ELTR . Patients and methods We have ﬁrst considered all data since 1968 to show the evolu-tion of results of LT in Europe since its initial development . Therest of the analysis has been undertaken during two differentperiods : ( a ) from January 1988 to December 2009 ( 89,865 LT –80,347 patients ) , where the date from January 1988 was chosenJournal of Hepatology 2012 vol . AIM To evaluate effective alternative antibiotics in treatment of cefotaxime-resistant spontaneous bacterial peritonitis . METHODS One hundred cirrhotic patients Output:	Due to the wide CrIs and the very low-certainty evidence for all the outcomes , significant benefits or harms of antibiotics are possible .
MS2906	*TASK* the task is to summarize an input biomedical literature in six sentences *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 For long-term treatment effects , patients with subacute back pain need to adhere to treatment recommendations beyond the prescribed exercise treatment . Adherence rates are as low as 30 % , so we developed a cognitive-behavioural training programme to enhance patients ' self-efficacy , maximise severity perceptions and reduce barrier perceptions . METHOD A 2 x 4 ( group x time ) repeated measurement design was applied . Forty-seven patients with non-specific , subacute back pain were r and omly assigned to a training group ( exercise treatment plus cognitive-behavioural training programme ) or a control group ( exercise treatment only ) . RESULTS Repeated measures ANOVA revealed significant main and interaction effects ; the training group reported enhanced self-efficacy and severity perceptions , reduced barrier perceptions , and self-reported that they exercised more often than the control group over time . However , no group differences regarding pain intensity emerged . CONCLUSION Our findings demonstrate that a short and inexpensive cognitive-behavioural training programme is an effective tool to enable back pain patients to follow treatment recommendations on a regular basis . PRACTICE IMPLICATION S The short and simple intervention can easily be conducted by personnel , other than psychologists , i.e. , physiotherapists This investigation was an initial attempt to explore psychological factors that might help or hinder the effect of exposure in vivo for patients with musculoskeletal pain and pain‐related fear . The study was based on data from a r and omized‐controlled trial for patients with non‐specific spinal pain ( Linton et al. , 2008 ) The objective of this study was to report on secondary analyses of a merged trial data set aim ed at exploring the potential importance of patient factors associated with clinical ly relevant improvements in non-acute , non-specific low back pain ( LBP ) . From 273 predominantly male army workers ( mean age 39 ± 10.5 years , range 20–56 years , 4 women ) with LBP who were recruited in three r and omized clinical trials , baseline individual patient factors , pain-related factors , work-related psychosocial factors , and psychological factors were evaluated as potential prognostic variables in a short-term ( post-treatment ) and a long-term logistic regression model ( 6 months after treatment ) . We found one dominant prognostic factor for improvement directly after treatment as well as 6 months later : baseline functional disability , expressed in Rol and –Morris Disability Question naire scores . Baseline fear of movement , expressed in Tampa Scale for Kinesiophobia scores , had also significant prognostic value for long-term improvement . Less strongly associated with the outcome , but also included in our final models , were supervisor social support and duration of complaints ( short-term model ) , and co-worker social support and pain radiation ( long-term model ) . Information about initial levels of functional disability and fear-avoidance behaviour can be of value in the treatment of patient population s with characteristics comparable to the current army study population ( e.g. , predominantly male , physically active , working , moderate but chronic back problems ) . Individuals at risk for poor long-term LBP recovery , i.e. , individuals with high initial level of disability and prominent fear-avoidance behaviour , can be distinguished that may need additional cognitive-behavioural treatment Study Design . A r and omized controlled design superimposed on treatment as usual was used to compare the effects of a cognitive-behavior intervention aim ed at preventing chronicity with two different forms of information . Objective . To develop a coping-oriented preventive intervention applicable in primary care , and to compare its impact with educational information . Summary of Background Data . Preventing long-term disability result ing from spinal pain has proved difficult . The information provided by health care professions and early interventions aim ed at preventing long-term disability may be important , but little scientific evidence exists concerning their use . Methods . A protocol for a six-session cognitive-behavior group intervention was developed on the basis of earlier research . The main focus was to prevent long-term disability by changing patients ’ behaviors and beliefs so they can cope better with their problems . Comparison groups received either a pamphlet shown earlier to have an effect , or a more extensive information package consisting of six installments . All the groups continued to receive treatment as usual in primary care . There were 243 patients with acute or subacute spinal pain who perceived that they were at risk for developing a chronic problem . These patients were r and omized to the cognitive-behavioral intervention or one of the two information groups . Because the aim was to prevent long-term disability , the key outcome variables at the 1-year follow-up assessment were sick absenteeism and health care use . Other variables were pain , function , fear-avoidance beliefs , and cognitions . Results . The comparison groups reported benefits . However , the risk for a long-term sick absence developing was lowered ninefold for the cognitive-behavior intervention group as compared with the risk for the information groups ( relative risk , 9.3 ) . Participants in the cognitive-behavior group also reported a significant decrease in perceived risk . In addition , the cognitive-behavior group demonstrated a significant decrease in physician and physical therapy use as compared with two groups receiving information , in which such use increased . All three groups tended to improve on the variables of pain , fear-avoidance , and cognitions . Conclusions . This study demonstrates that a cognitive-behavior group intervention can lower the risk of a long-term disability developing . These findings underscore the significance of early interventions that specifically aim to prevent chronic problems . This approach might be applied to primary care setting Introduction It was postulated that workers , at the sub-acute stage after injury , respond differently to clinical and occupational interventions offered in a workers ’ compensation environment . Individual worker risk of disability , it was further believed , would influence the effectiveness of early intervention . The objective of the current pilot study was to evaluate return to work ( RTW ) outcomes following proactive , combined clinical , occupational and case management-based interdisciplinary early intervention , provided in a workers ’ compensation environment 4–10 weeks of onset of back pain , to workers with medium and high risk for disability . Methods The project was a controlled study comparing conventional workers ’ compensation case management with integrated , interdisciplinary and multimodal early intervention ( hereinafter referred to as “ EI ” ) . At baseline , risk status was determined by a vali date d Risk for Disability Question naire by Carragee et al. ( Spine 5(1):24–35 , 2005 ) . Seventeen workers at high risk of protracted disability and 20 workers at moderate risk of disability received conventional case management , and 17 workers assessed at high risk of protracted disability and 18 workers at moderate risk of disability received the Early Intervention . Results At 3 months post back pain onset , no statistically significant differences were identified in RTW outcomes between conventional case management and the Early Intervention . However , by 6 months post back pain onset , workers at high risk of work disability who received the Early Intervention were significantly more likely to RTW than high risk workers who received conventional case management . In contrast , moderate risk workers continued to exhibit no statistically significant differences in RTW outcomes . Conclusion Multimodal Early Intervention in the workers ’ compensation case management context is likely effective for workers with sub-acute back pain who are at high risk of occupational disability . The comprehensive Early Intervention is , however , likely redundant for workers who are not at high risk for disability and should not be applied indiscriminately . Further studies are required to determine longer-term Early Intervention outcomes , and to replicate the findings using a r and omized control design . Also , with a larger sample size , it will be possible to determine predictors of occupational outcomes In a prospect i ve trial , 222 adults with low-back pain of at least 2 weeks ' duration in a Health Maintenance Organization ( HMO ) were r and omly assigned to usual care ( UC ) , a 4-hour back school psychoeducational session ( LBS ) , or the same back school plus a 1-year “ compliance package ” program design ed to encourage appropriate self-management for back pain ( CP ) . Sixty-four percent of LBS and CP subjects attended their back school sessions . Follow-up measurement of pain level ( using the Visual Analogue Scale ) , functional status ( using the Sickness Impact Profile ) , and various other indicators of health status showed no measurable effect of either treatment condition ( LBS or CP ) compared with UC at 3 , 6 , 12 , and 18 months after entry into the study . Initial disability resolved by 3 months in most patients , and a minority of subjects ( 10–15 % ) showed residual or recurrent functional Impairment 1 year after entry . Health care utilization tended to be slightly higher after intervention In the CP group . With or without follow-up encouragement , back school instructions given in a single 4-hour session had no measurable impact on the comfort or functional status of the majority of patients with new onset back pain in this HMO Abstract Psychological factors consistent with fear‐avoidance models are associated with the development of chronic low back pain ( LBP ) . As a result , grade d activity ( GA ) and grade d exposure ( GX ) have been suggested as behavioral treatment options . This clinical trial compared the effectiveness of treatment‐based classification ( TBC ) physical therapy alone to TBC augmented with GA or GX for patients with acute and sub‐acute LBP . Our primary hypothesis was that GX would be most effective for those with elevated pain‐related fear . In total , 108 patients enrolled in this clinical trial and were r and omly assigned to receive TBC , GA , or GX . Outcomes were assessed by a blinded evaluator at 4 weeks and by mail at 6 months . The primary outcomes for this trial were disability and pain intensity , and the secondary outcomes were fear‐avoidance beliefs , pain catastrophizing , and physical impairment . There were no differences in 4‐week and 6‐month outcomes for reduction of disability , pain intensity , pain catastrophizing , and physical impairment . GX and TBC were associated with larger reductions in fear‐avoidance beliefs at 6 months only . Six‐month reduction in disability was associated with reduction in pain intensity , while 6‐month reduction in pain intensity was associated with reductions in fear‐avoidance beliefs and pain catastrophizing . This trial suggests that supplementing TBC with GA or GX was not effective for improving important outcomes related to the development of chronic LBP A clinical prediction rule to identify patients most likely to respond to spinal manipulation has been published and widely cited but requires further testing for external validity . We performed a pre-planned secondary analysis of a r and omised controlled trial investigating the efficacy of spinal manipulative therapy in 239 patients presenting to general practice clinics for acute , non-specific , low back pain . Patients were r and omised to receive spinal manipulative therapy or placebo 2 to 3 times per week for up to 4 weeks . All patients received general practitioner care ( advice and paracetamol ) . Outcomes were pain and disability measured at 1 , 2 , 4 and 12 weeks . Status on the clinical prediction rule was measured at baseline . The clinical prediction rule performed no better than chance in identifying patients with acute , non-specific low back pain most likely to respond to spinal manipulative therapy ( pain P = 0.805 , disability P = 0.600 ) . At 1-week follow-up , the mean difference in effect of spinal manipulative therapy compared to placebo in patients who were rule positive rather than rule negative was 0.3 points less on a 10-point pain scale ( 95 % CI −0.8 to 1.4 ) . The clinical prediction rule proposed by Childs et al. did not generalise to patients presenting to primary care with acute low back pain who received a course of spinal manipulative therapy STUDY DESIGN A double-blind , r and omized controlled trial of a novel educational booklet compared with a traditional booklet for patients seeking treatment in primary care for acute or recurrent low back pain . OBJECTIVE To test the impact of a novel educational booklet on patients ' beliefs about back pain and functional outcome . SUMMARY OF BACKGROUND DATA The information and advice that health professionals give to patients may be important in health care intervention , but there is little scientific evidence of their effectiveness . A novel patient educational booklet , The Back Book , has been developed to provide evidence -based information and advice consistent with current clinical guidelines . METHODS One hundred sixty-two patients were given either the experimental booklet or a traditional booklet . The main outcomes studied were fear-avoidance beliefs about physical activity , beliefs about the inevitable consequences of back trouble , the Rol and Disability Question naire , and visual analogue pain scales . Postal follow-up response at 1 year after initial treatment was 78 % . RESULTS Patients receiving the experimental booklet showed a statistically significant greater early improvement in beliefs which was maintained at 1 year . A greater proportion of patients with an initially high fear-avoidance beliefs score who received the experimental booklet had clinical ly important improvement in fear-avoidance beliefs about physical activity at 2 weeks , followed by a clinical ly important improvement in the Rol and Disability Question naire score at 3 months . There was no effect on pain . CONCLUSION This trial shows that carefully selected and presented information and advice about back pain can have a positive effect on patients ' beliefs and clinical outcomes , and suggests that a study of clinical ly important effects in individual patients may provide further insights into the management of low back pain & NA ; The effects of outpatient group cognitive therapy , relaxation training , and cognitive therapy in combination with relaxation training on chronic low back pain and associated physical and psychosocial disability were evaluated and compared . One‐hundred and two mildly disabled chronic low back pain patients were assigned r and omly to a waiting‐list ( WL ) control condition and the 3 treatments . Patient self‐report and observational measures were obtained pretreatment and post‐treatment for all conditions , and at 6‐ and 12‐month follow‐ups for the treatment conditions . Pain intensity decreased significantly pre‐ to post‐treatment for patients in all 3 treatment conditions , but not the WL condition . Depressive symptoms and disability improved significantly in all conditions ( including the waiting list ) from pretreatment to post‐treatment , with no statistically significant differences among treatments . At both follow‐ups , all 3 treatment groups remained significantly improved from pretreat Output:	Grade d activity plus Treatment Based Classification targeted to people with high movement-related fear was more effective than Treatment Based Classification at reducing movement-related fear at 4 weeks . Active rehabilitation ( physical exercise classes with cognitive-behavioural principles ) was more effective than usual GP care at reducing activity limitation at 12 months , when targeted to people with higher movement-related pain .
MS2907	*TASK* the task is to summarize an input biomedical literature in six sentences *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 column presents preliminary findings of an intervention to support shared decision making in psychopharmacology consultation . The waiting area in an urban psychiatric medication clinic was transformed into a peer-run Decision Support Center featuring a user-friendly , Internet-based software program with which clients could create a one-page computer-generated report for use in the medication consultation . The Decision Support Center was used 662 times by 189 unique users from a young-adult and general adult case management team from October 2006 to September 2007 . All clients had severe mental disorders . Only ten clients refused to use the intervention at some point during the pilot study . Focus groups with medical staff ( N=4 ) , clients ( N=16 ) , case managers ( N=14 ) , and peer-specialist staff ( N=3 ) reported that the intervention helped to create efficiencies in the consultation and empower clients to become more involved in treatment-related decision making . A r and omized controlled trial is currently in process We investigated associations between adult attachment , symptoms and interpersonal functioning , including therapeutic relationships in 96 patients with psychosis . Using a prospect i ve design , we also assessed changes in attachment in both psychiatrically unstable and stable groups . We measured attachment using the Psychosis Attachment Measure ( PAM ) and interpersonal problems and therapeutic relationships were assessed from both psychiatric staff and patient perspectives . Avoidant attachment was associated with positive symptoms , negative symptoms and paranoia . Attachment ratings were relatively stable over time , although changes in attachment anxiety were positively correlated with changes in symptoms . Predicted associations between high levels of attachment anxiety and avoidance and interpersonal problems were supported , and attachment avoidance was associated with difficulties in therapeutic relationships . Findings suggest that adult attachment style is a meaningful individual difference variable in people with psychosis and may be an important predictor of symptoms , interpersonal problems and difficulties in therapeutic relationships over and above severity of illness BACKGROUND A better therapeutic relationship predicts better outcomes . However , there is no trial-based evidence on how to improve therapeutic relationships in psychosis . AIMS To test the effectiveness of communication training for psychiatrists on improving shared underst and ing and the therapeutic relationship ( trial registration : IS RCT N94846422 ) . METHOD In a cluster r and omised controlled trial in the UK , 21 psychiatrists were r and omised . Ninety-seven ( 51 % of those approached ) out- patients with schizophrenia/schizoaffective disorder were recruited , and 64 ( 66 % of the sample recruited at baseline ) were followed up after 5 months . The intervention group received four group and one individualised session . The primary outcome , rated blind , was psychiatrist effort in establishing shared underst and ing ( self-repair ) . Secondary outcome was the therapeutic relationship . RESULTS Psychiatrists receiving the intervention used 44 % more self-repair than the control group ( adjusted difference in means 6.4 , 95 % CI 1.46 - 11.33 , P<0.011 , a large effect ) adjusting for baseline self-repair . Psychiatrists rated the therapeutic relationship more positively ( adjusted difference in means 0.20 , 95 % CI 0.03 - 0.37 , P = 0.022 , a medium effect ) , as did patients ( adjusted difference in means 0.21 , 95 % CI 0.01 - 0.41 , P = 0.043 , a medium effect ) . CONCLUSIONS Shared underst and ing can be successfully targeted in training and improves relationships in treating psychosis Background The quality of the therapeutic alliance ( TA ) has been invoked to explain the equal effectiveness of different psychotherapies , but prior research is correlational , and does not address the possibility that individuals who form good alliances may have good outcomes without therapy . Method We evaluated the causal effect of TA using instrumental variable ( structural equation ) modelling on data from a three-arm , r and omized controlled trial of 308 people in an acute first or second episode of a non-affective psychosis . The trial compared cognitive behavioural therapy ( CBT ) over 6 weeks plus routine care ( RC ) v. supportive counselling ( SC ) plus RC v. RC alone . We examined the effect of TA , as measured by the client-rated CALPAS , on the primary trial 18-month outcome of symptom severity ( PANSS ) , which was assessed blind to treatment allocation . Results Both adjunctive CBT and SC improved 18-month outcomes , compared to RC . We showed that , for both psychological treatments , improving TA improves symptomatic outcome . With a good TA , attending more sessions causes a significantly better outcome on PANSS total score [ effect size −2.91 , 95 % confidence interval ( CI ) −0.90 to −4.91 ] . With a poor TA , attending more sessions is detrimental ( effect size + 7.74 , 95 % CI + 1.03 to + 14.45 ) . Conclusions This is the first ever demonstration that TA has a causal effect on symptomatic outcome of a psychological treatment , and that poor TA is actively detrimental . These effects may extend to other therapeutic modalities and disorders Background Long acting injections ( LAI ) have been associated with perceptions of coercion in cross sectional studies but there have been no longitudinal studies of the effects on clinical relationships with newer depot medications . Method R and omized controlled trial with ( 50 ) participants with a diagnosis of schizophrenia r and omized to risperidone LAI or oral atypical antipsychotic medication . The main outcome was the Working Alliance Inventory ( WAI ) with background variables ( symptoms , side effect , social functioning , quality of life ) measured before r and omization and at two years . Results At follow-up ( 14 risperidone LAI and 16 oral medication ) analyses including predictors of missing data and baseline score showed a trend for those on risperidone LAI to reduce WAI score and those on oral medication showing no change . Sensitivity analyses showed ( i ) a significant detrimental effect of LAI on WAI and ( ii ) the pattern of results was not affected by change in symptoms over the study . Conclusion This is the first study to show that the prescription of depot atypical depot medication is associated with detrimental effects on clinical relationships after 2 years of continual treatment BACKGROUND The CRIMSON ( CRisis plan IMpact : Subjective and Objective coercion and eNgagement ) study is an individual level , r and omised controlled trial that compared the effectiveness of Joint Crisis Plans ( JCPs ) with treatment as usual for people with severe mental illness . The JCP is a negotiated statement by a patient of treatment preferences for any future psychiatric emergency , when he or she might be unable to express clear views . We assessed whether the additional use of JCPs improved patient outcomes compared with treatment as usual . METHODS Patients were eligible if they had at least one psychiatric admission in the previous 2 years and were on the Enhanced Care Programme Approach register . The study was done with 64 generic and specialist community mental health teams in four English mental health care provider organisations ( trusts ) . Hypotheses tested were that , compared with the control group , the intervention group would experience : fewer compulsory admissions ( primary outcome ) ; fewer psychiatric admissions ; shorter psychiatric stays ; lower perceived coercion ; improved therapeutic relationships ; and improved engagement . We stratified participants by centre . The research team but not participants nor clinical staff were masked to allocation . This study is registered with Clinical Trials.gov , number IS RCT N11501328 . FINDINGS 569 participants were r and omly assigned ( 285 to the intervention group and 284 to the control group ) . No significant treatment effect was seen for the primary outcome ( 56 [ 20 % ] sectioned in the control group and 49 [ 18 % ] in the JCP group ; odds ratio 0·90 [ 95 % CI 0·58 - 1·39 , p=0·63 ] ) or any secondary outcomes , with the exception of an improved secondary outcome of therapeutic relationships ( 17·3 [ 7·6 ] vs 16·0 [ 7·1 ] ; adjusted difference -1·28 [ 95 % CI -2·56 to -0·01 , p=0·049 ] ) . Qualitative data supported this finding . INTERPRETATION Our findings are inconsistent with two earlier JCP studies , and show that the JCP is not significantly more effective than treatment as usual . There is evidence to suggest the JCPs were not fully implemented in all study sites , and were combined with routine clinical review meetings which did not actively incorporate patients ' preferences . The study therefore raises important questions about implementing new interventions in routine clinical practice . FUNDING Medical Research Council UK and the National Institute for Health Research Psychoeducation improves adherence and motivates patients to accept a maintenance therapy as recommended by the guidelines . This would mean a daily consumption of at least 300 chlorpromazine ( CPZ ) units in the long run and should lead to an increase of the antipsychotic dosage in comparison to patients with treatment as usual ( TAU ) . This raises 2 important questions : whether more side effects are provoked and do the patients have a corresponding benefit with a better outcome . A total of 41 patients with a diagnosis of schizophrenic or schizoaffective disorder were r and omized at study entry , either to bifocal psychoeducation ( 21 ) , or to st and ard treatment ( 20 ) . They were compared concerning compliance , type of medication , dosage ( CPZ equivalents ) , motor side effects and number of days in hospital . The average daily antipsychotic medication 2 and 7 years after index discharge was 365 and 354 CPZ-units respectively in the intervention group ( IG ) , but 247 and 279 , respectively in the control group ( CG ) . The extent of motor side effects was slightly smaller in the IG , but they showed a small and statistically not significant increase in the rate of tardive dyskinesia ( TD ) after 7 years . At the 7-year follow-up the patients in the IG had spent 74.7 days in hospital compared to 243.4 days for the patients in the CG ( P < .05 ) . The course of illness was significantly better in the IG without increasing motor side-effects . Therefore , psychoeducation should be integrated more systematic ally into the routine treatment . These data are part of a previous study , published 2007 , with a sample size of 48 patients . Seven patients -3 of the IG and 4 of the CG-could not be included , because they were not able to complete the very complex " Computer-based kinematic analysis of motor performance . " In this article all conclusions are referred to the new sample size , therefore some results are slightly different in comparison to the previous data The importance of therapeutic alliance in predicting treatment outcomes is well established , but less is known about client characteristics that predict alliance . Clients with co-occurring psychosis and substance misuse ( n = 116 ) who received integrated motivational interviewing and cognitive behavior therapy in the context of a large r and omized controlled trial completed the Working Alliance Inventory . Their trial therapists also completed Working Alliance Inventories . Rating perspectives were compared , and in a cross-sectional study , client predictors of therapeutic alliance were examined . As hypothesized , clients ' negative attitudes to treatment , including lack of insight , were predictive of poorer alliance . Therapist-rated alliance was also predicted by the client 's attitude to medication , self-reported depression , and living situation . Symptom severity and substance use measures were unrelated to alliance . Consistent with previous studies , rating perspectives differed , with clients rating alliance more positive than therapists This study examined the relationship of the therapeutic alliance to the treatment course and outcome of 143 patients with nonchronic schizophrenia . Results showed that patients who formed good alliances with their therapists within the first 6 months of treatment were significantly more likely to remain in psychotherapy , comply with their prescribed medication regimens , and achieve better outcomes after 2 years , with less medication , than patients who did not . These results underscored the prognostic value of assessing the alliance and the need to identify factors that contribute to its development and maintenance with schizophrenic patients OBJECTIVES Outpatient and inpatient mental health service outcomes for out patients with schizophrenia or schizoaffective disorder who received psychoeducational multiple-family group treatment were compared with outcomes for similar patients who received st and ard care . METHODS A total of 106 out patients with schizophrenia or schizoaffective disorder who were receiving services from a large community mental health center were r and omly assigned to receive st and ard care or st and ard care plus multiple-family group treatment . The two-year multiple-family intervention consisted of weekly group sessions design ed to educate patients and their family members about the biological basis of mental illness and treatment , to improve illness management and coping skills , and to provide social support . The group sessions were conducted by two clinicians using a st and ardized protocol . Each multiple-family group included five to eight families and consumers . Service records for the year before and after r and om assignment to the study groups were examined in an intent-to-treat analysis . RESULTS During the year after r and om assignment to study groups , multiple-family group treatment was associated with a lower rate of psychiatric hospitalization than st and ard care . It was only marginally associated with lower use of crisis services , and it was not associated with the amount of outpatient service time . CONCLUSIONS The findings suggest that implementation of multiple-family group treatment in a capitated community mental health setting improves hospitalization outcomes without increasing the overall volume of outpatient mental health services Output:	The quality of therapeutic alliance correlates with clinical symptoms , insight , social and family support , the therapist 's qualities , the availability of shared therapeutic decision making , and the types of hospitalization . Although current evidence needs to be completed with further studies , it is already clear that group and family psychoeducation , cognitive remediation , community-based psychiatric services , and shared therapeutic decision making are essential approaches in the management of patients with psychosis
MS2908	*TASK* the task is to summarize an input biomedical literature in six sentences *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 recently published the results of a r and omised controlled trial of a nurse telephone consultation service in primary care out of hours.1 The new service , operating at evenings and weekends , significantly reduced general practitioners ’ workload and was at least as safe as the existing out of hours service . Contacts diminish sharply after about 10 pm,2 and , anecdotally , a higher proportion of night calls necessitate consultation with a general practitioner . We report here a parallel trial aim ed at establishing whether nurse telephone consultation was equally effective in managing workload at night Objective : To investigate the potential impact for ambulance services of telephone assessment and triage for callers who present with non-serious problems ( Category C calls ) as classified by ambulance service call takers . Design : Pragmatic controlled trial . Calls identified using priority dispatch protocol s as non-serious were allocated to intervention and control groups according to time of call . Ambulance dispatch occurred according to existing procedures . During intervention sessions , nurses or paramedics within the control room used a computerised decision support system to provide telephone assessment , triage and , if appropriate , offer advice to permit estimation of the potential impact on ambulance dispatch . Setting : Ambulance services in London and the West Midl and s. Subjects : Patients for whom emergency calls were made to the ambulance services between April 1998 and May 1999 during four hour sessions sample d across all days of the week between 0700 and 2300 . Main outcome measures : Triage decision , ambulance cancellation , attendance at an emergency department . Results : In total , there were 635 intervention calls and 611 controls . Of those in the intervention group , 330 ( 52.0 % ) were triaged as not requiring an emergency ambulance , and 119 ( 36.6 % ) of these did not attend an emergency department . This compares with 55 ( 18.1 % ) of those triaged by a nurse or paramedic as requiring an ambulance ( odds ratio 2.62 ; 95 % CI 1.78 to 3.85 ) . Patients triaged as not requiring an emergency ambulance were less likely to be admitted to an inpatient bed ( odds ratio 0.55 ; 95 % CI 0.33 to 0.93 ) , but even so 30 ( 9.2 % ) were admitted . Nurses were more likely than paramedics to triage calls into the groups classified as not requiring an ambulance . After controlling for age , case mix , time of day , day of week , season , and ambulance service , the results of a logistic regression analysis revealed that this difference was significant with an odds ratio for nurses : paramedics of 1.28 ( 95 % CI 1.12 to 1.47 ) . Conclusions : The findings indicate that telephone assessment of Category C calls identifies patients who are less likely to require emergency department care and that this could have a significant impact on emergency ambulance dispatch rates . Nurses were more likely than paramedics to assess calls as requiring an alternative response to emergency ambulance despatch , but the extent to which this relates to aspects of training and professional perspective is unclear . However , consideration should be given to the acceptability , reliability , and cost consequences of this intervention before it can be recommended for full evaluation BACKGROUND Telephone working is an increasingly important way of managing general practice workload , particularly out of hours . The role of telephone triage , however , in managing acute consultations during the day has not been adequately research ed . AIM To determine the impact of telephone triage , conducted by a practice nurse , on the management of same day consultations in a general practice . METHOD A general practice of 11,300 patients in South Tyneside collected prospect i ve telephone and surgery consultation data over three months . Patient satisfaction , for those who had received only telephone advice , was measured using a postal question naire . Four outcomes were measured : changes in doctor and nurse workload ; repeat consultations with the same problem ; prescriptions issued ; and patient satisfaction with the service . RESULTS In three months , 1263 consultations were recorded . Doctor workload fell by 54 % , from 1522 to 664 consultations , compared with the previous three months . A total of 325 ( 26 % ) telephone requests to see the doctor were managed by the nurse on the telephone without them visiting the surgery . Also , 273 ( 21 % ) patients saw the nurse in the surgery , 565 ( 45 % ) saw the doctor in the surgery , and 99 ( 8 % ) saw the doctor and the nurse in the surgery . The response rate to the postal question naire was 192/271 ( 71 % ) ; 154 ( 88 % ) were satisfied with nurse telephone advice . CONCLUSIONS Telephone triage , by a practice nurse , of patients who wish to see the doctor on the same day , reduced doctor workload . This was a service that patients liked Abstract Objective : To undertake an economic evaluation of nurse telephone consultation using decision support software in comparison with usual general practice care provided by a general practice cooperative . Design : Cost analysis from an NHS perspective using stochastic data from a r and omised controlled trial . Setting : General practice cooperative with 55 general practitioners serving 97 000 registered patients in Wiltshire , Engl and . Subjects : All patients contacting the service , or about whom the service was contacted during the trial year ( January 1997 to January 1998 ) . Main outcome measures : Costs and savings to the NHS during the trial year . Results : The cost of providing nurse telephone consultation was £ 81 237 per annum . This , however , determined a £ 94 422 reduction of other costs for the NHS arising from reduced emergency admissions to hospital . Using point estimates for savings , the cost analysis , combined with the analysis of outcomes , showed a dominance situation for the intervention over general practice cooperative care alone . If a larger improvement in outcomes is assumed ( upper 95 % confidence limit ) NHS savings increase to £ 123 824 per annum . Savings of only £ 3728 would , however , arise in a scenario where lower 95 % confidence limits for outcome differences were observed . To break even , the intervention would have needed to save 138 emergency hospital admissions per year , around 90 % of the effect achieved in the trial . Additional savings of £ 16 928 for general practice arose from reduced travel to visit patients at home and fewer surgery appointments within three days of a call . Conclusions : Nurse telephone consultation in out of hours primary care may reduce NHS costs in the long term by reducing dem and for emergency admission to hospital . General practitioners currently bear most of the cost of nurse telephone consultation and benefit least from the savings associated with it . This indicates that the service produces benefits in terms of service quality , which are beyond the reach of this cost analysis BACKGROUND General practitioners ( GPs ) in the United Kingdom have recently begun to adopt the use of telephone consultation during daytime surgery as a means of managing dem and , particularly requests for same-day appointments . However , it is not known whether the strategy actually reduces GP workload . AIM To investigate how the use of telephone consultations impacts on the management of requests for same-day appointments , on re source use , indicators of clinical care , and patient perceptions of consultations . DESIGN OF STUDY R and omised controlled trial . SETTING All patients ( n = 388 ) seeking same-day appointments in each surgery in two urban practice s ( total population = 10,420 ) over a four-week period . METHOD The primary outcome measure was use of doctor time for the index telephone or face-to-face consultation . Secondary outcomes were subsequent use of investigations and of services in the two-week period following consultation , frequency of blood pressure measurement and antibiotic prescriptions , and number of problems considered at consultation . Patient perceptions were measured by the Patient Enablement Instrument ( PEI ) and reported willingness to use telephone consultations in the future . RESULTS Telephone consultations took less time ( 8.2 minutes versus 6.7 minutes ; diff = 1.5 , 95 % confidence interval [ CI ] = 0.6 to 2.4 , P = 0.002 ) . Patients consulting by telephone reconsulted the GP more frequently in the two weeks that followed ( 0.6 consultations versus 0.4 consultations ; diff = 0.2 , 95 % CI = 0.0 to 0.3 , P = 0.01 ) . Blood pressure was measured more often in the group of patients managed face-to-face ( 25/188 [ 13.3 % ] versus 12/181 [ 6.6 % ] ; diff = 6.7 % , 95 % CI = 0.6 % to 12.7 % ) . There was no significant difference in patient perceptions or other secondary outcomes . CONCLUSION Use of telephone consultations for same-day appointments was associated with time saving , and did not result in lower PEI scores . Possibly , however , this short-term saving was offset by higher re-consultation and less use of opportunistic health promotion BACKGROUND Advice nurse call centers are used to ensure access to medical advice , thereby potentially reducing the costs of health services . OBJECTIVE To determine if medical advice from advice nurses and on-call physicians delays significant medical treatment in a general pediatrics population . DESIGN R and omized controlled trial . SETTING A university general pediatrics faculty practice . PARTICIPANTS Parents or guardians calling for after-hours advice regarding their children . Intervention After-hours medical advice calls were r and omized at the time of the call to an advice nurse or an on-call pediatrician . MAIN OUTCOME MEASURES The proportion of callers who sought medical care not advised by the advice nurse or on-call pediatrician and the proportion who received unadvised significant care . RESULTS There were 1182 advice calls : 566 in the pediatrician group and 616 in the advice nurse group . There were no significant differences in the types of telephone triage advice in the physician and advice nurse groups . There was no significant difference in the proportion of callers who sought unadvised care ( 108 [ 19.9 % ] in the physician group vs 110 [ 19.0 % ] in the advice nurse group ) or in the proportion of callers who received unadvised significant care ( 23 [ 4.2 % ] in the physician group vs 25 [ 4.3 % ] in the advice nurse group ) . CONCLUSIONS The proportions of callers who sought unadvised medical care and who received unadvised significant care were not significantly different in the advice nurse and pediatrician groups . This suggests that advice nurses do not delay significant medical treatment when compared with pediatricians Objective . Telephone triage programs are becoming very common at children 's hospitals across the nation . One of the proposed benefits of these programs is the more efficient use of health care re sources by triaging patients to the appropriate level of health care . The purpose of this study is to examine the appropriateness of referrals to a pediatric emergency department ( ED ) by the Pediatric Health Information Line ( PHIL ) , a hospital-based telephone triage program , versus all other sources of referrals . Methods . A blinded Delphi rating system was used to review the physician 's sheets of 133 consecutive ED referrals by PHIL for medical appropriateness . A total of 260 r and omly selected control patients seen in the ED during the same period were similarly review ed . If 2 of 3 pediatric emergency medicine physicians agreed that an ED visit was appropriate , then it was considered appropriate . A comparison of the 2 groups ' ED appropriateness was made using a contingency table χ2 test . An odds ratio with confidence limits was also calculated . Demographic data were collected for both groups including age , race , gender , and insurance status . Results . The PHIL group had an appropriateness rate of 80.2 % , compared with 60.5 % for the control group ( χ2 = 14.6369 ; odds ratio = 2.65 ; 95 % confidence interval [ 1.5759,4.5008 ] ) . Conclusions . This demonstrated that for the period studied , PHIL referrals to the ED had a 33 % higher rate of appropriateness than controls . This evidence supports telephone triage as an efficient gatekeeper for health care re sources Abstract Objective : To compare the outcome of out of hours care given by general practitioners from patients ' own practice s and by commercial deputising services . Design : R and omised controlled trial . Setting : Four urban areas in Manchester , Salford , Stockport , and Leicester . Subjects : 2152 patients who requested out of hours care , and 49 practice doctors and 183 deputising doctors ( 61 % local principals in general practice ) who responded to the requests . Main outcome measures : Health status outcome , patient satisfaction , and subsequent health service use . Results : Patients seen by deputising doctors were less satisfied with the care they received . The mean overall satisfaction score for practice doctors was 70.7 ( 95 % confidence interval 68.1 to 73.2 ) and for deputising doctors 61.8 ( 59.9 to 63.7 ) . The greatest difference in satisfaction was with the delay in visiting . There were no differences in the change in health or overall health status measured 24 to 120 hours after the out of hours call or subsequent use of the health service in the two groups . Conclusions : Patients are more satisfied with the out of hours care provided by practice doctors than that provided by deputising doctors . Organisation of doctors into large groups may produce lower levels of patient satisfaction , especially when associated with increased delays in the time taken to visit . There seem to be no appreciable differences in health outcome between the two types of service . Key messages Between 24 and 120 hours after a request for out of hours care patients cared for by deputising services and practice doctors show no difference in health status There is no difference in health service use between the two groups in the two weeks after a request for out of hours care Patients are more satisfied with out of hours care provided by their own practice doctors Though Output:	REVIEW ERS ' CONCLUSIONS Telephone consultation appears to reduce the number of surgery contacts and out-of-hours visits by general practitioners .
MS2909	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Brief interventions for problem drinking in medical setting s are effective but rarely conducted , mainly due to insufficient time . A stepped care approach ( starting with a very brief intervention and intensifying efforts in case of no success ) could save re sources and enlarge effectiveness ; however , research is lacking . The present study compares a full care brief intervention for patients with at-risk drinking , alcohol abuse or dependence with a stepped care approach in a r and omized controlled trial . METHODS Participants were proactively recruited from general practice s in two northern German cities . In total , 10,803 screenings were conducted ( refusal rate : 5 % ) . Alcohol use disorders according to DSM-IV were assessed with the Munich-Composite International Diagnostic Interview ( M-CIDI ) . Eligible participants were r and omly assigned to one of three conditions : ( 1 ) stepped care ( SC ) : a computerized intervention plus up to three 40-min telephone-based interventions depending on the success of the previous intervention ; ( 2 ) full-care ( FC ) : a computerized intervention plus a fixed number of four 30-min telephone-based interventions that equals the maximum of the stepped care intervention ; ( 3 ) an untreated control group ( CG ) . Counseling effort in the intervention conditions and quantity/frequency of drinking were assessed at 12-month follow-up . RESULTS SC participants received roughly half of the amount of intervention in minutes compared to FC participants . Both groups did not differ in drinking outcomes . Compared to CG , intervention showed small to medium effect size for at-risk drinkers . CONCLUSIONS Study results reveal that a stepped care approach can be expected to increase cost-effectiveness of brief interventions for individuals with at-risk drinking STUDY OBJECTIVE This study compares the effect of a brief motivational intervention for alcohol plus a booster given to emergency department ( ED ) patients with subcritical injuries from a motor vehicle crash with the effect of brief motivational intervention for alcohol plus a booster in patients treated for non-motor vehicle crash-related injuries . METHODS A r and omized controlled trial ( n=539 ) was conducted at an urban Level I trauma center of brief intervention ( 1 ED session of brief intervention ) , brief motivational intervention for alcohol plus a booster ( 1 ED session plus booster session ) , or st and ard care for injured ED patients with an alcohol use problem who were being discharged home . At 12 months , alcohol-related negative consequences and injuries were measured . We performed a secondary analysis comparing motor vehicle crash-injured patients and non-motor vehicle crash-injured patients in the study sample . RESULTS Subcritically injured ED patients with harmful or hazardous alcohol use who received brief motivational intervention for alcohol plus a booster had fewer alcohol-related negative consequences and alcohol-related injuries than those receiving brief intervention or st and ard care at 12-month follow-up ( previously reported ) . A secondary analysis of this result showed that motor vehicle crash patients ( n=133 ) given brief motivational intervention for alcohol plus a booster ( n=34 ) had fewer alcohol-related injuries than those receiving st and ard care ( n=46 ; P = .001 ) . Moreover , there were no significant differences in alcohol-related injuries among the non-motor vehicle crash-injured patients who received brief intervention or st and ard care . CONCLUSION Brief motivational intervention for alcohol plus a booster is a useful intervention for subcritically injured ED patients with harmful or hazardous alcohol use . Its effects may be moderated by the cause of injury OBJECTIVE Alcohol screening and brief intervention ( SBI ) has gained widespread acceptance as an effective method for reducing problem drinking in at-risk population s. This study examines the cost and cost-effectiveness of an SBI pilot program delivered in an inner-city hospital emergency department ( ED ) to a traditionally underserved population . METHOD A total of 1,036 subjects were screened for problem drinking during their visit to an ED . Eligible participants ( N = 294 ) were r and omly assigned to either a brief intervention group or a control group . As the result of attrition , a final sample of 194 ( 90 brief intervention ; 104 control ) participants remained at follow-up . The intervention consisted of a brief counseling session and a health information packet . The control group received only the packet . Intervention cost data were collected and analyzed using the Drug Abuse Treatment Cost Analysis Program . Selected outcomes at the 3-month follow-up included the raw Alcohol Use Disorders Identification Test score , average weekly number of drinks and engaging in heavy drinking in the past month ( > 6 drinks on one occasion for men , > 4 for women ) . Outcome differences between the intervention and control groups were estimated with both bivariate and multivariate techniques . RESULTS The average economic cost of the brief intervention was dollars 632 per subject , of which screening ( dollars 497 ) was the largest component . In all cases , intervention subjects had better 3-month outcomes than control subjects , but the differences were not always statistically significant . Cost-effectiveness ratios were relatively small for all three outcomes , suggesting this type of intervention has the potential to be cost-effective under full implementation . CONCLUSIONS The preliminary results demonstrate the potential advantage of further research in this area with larger sample s and a longer follow-up period AIM To establish the efficacy of a brief motivational intervention compared to feedback only when delivered in an emergency department for reducing alcohol use and problems among young adults . DESIGN Two-group r and omized controlled trial with follow-up assessment s at 6 and 12 months . SETTING Level I Trauma Center . PARTICIPANTS A total of 198 18 - 24-year-old patients who were either alcohol positive upon hospital admission or met screening criteria for alcohol problems . INTERVENTION Participants were assigned r and omly to receive a one-session motivational intervention ( MI ) that included personalized feedback , or the personalized feedback report only ( FO ) . All participants received additional telephone contact 1 month and 3 months after baseline . MEASUREMENTS Demographic information , alcohol use , alcohol problems and treatment seeking . FINDINGS Six months after the intervention MI participants drank on fewer days , had fewer heavy drinking days and drank fewer drinks per week in the past month than did FO patients . These effects were maintained at 12 months . Clinical significance evaluation indicated that twice as many MI participants as FO participants reliably reduced their volume of alcohol consumption from baseline to 12 months . Reductions in alcohol-related injuries and moving violations , and increases in alcohol treatment-seeking were observed across both conditions at both follow-ups with no differences between conditions . CONCLUSIONS This study provides new data supporting the potential of the motivational intervention tested to reduce alcohol consumption among high-risk youth AIMS This study aim ed at testing the effectiveness of a brief motivational intervention ( BI ) compared with a minimal intervention ( MI ) for reducing alcohol consumption in adult , alcohol-positive traffic casualties . METHODS Patients were recruited at the emergency room of a trauma hospital and screened for alcohol by a qualitative saliva test ( positive from a blood alcohol concentration of 0.02 g/l ) . Positive patients ( 13.3 % ) who accepted entering the study were r and omly allocated into BI and MI . Baseline assessment was the same for all patients . Blind telephone follow-ups were performed at months 3 , 6 , and 12 , and results were analysed by protocol and by intention-to-treat analysis . RESULTS After 1 year of follow-up , 67 % of the patients had reduced their consumption , the percentage of heavy drinkers had dropped by 47 % , and 62 % of baseline AUDIT-C positive patients ( hazardous drinkers ) had become negative . Binge drinking dropped significantly ( P < 0.05 ) . Results at month 12 were in line with the previous ones . CONCLUSIONS The effectiveness of BI compared with MI has not been verified , but a significant reduction in consumption has been observed in the whole sample , without significant differences by type of intervention . The persistence and dimension of changes suggest a real effect of both interventions , although the lack of a pure control group does not allow definitive conclusions . Traffic casualties are in a teachable moments to benefit from easy and cheap interventions Objectives : Brief intervention for excessive alcohol consumption is effective yet not implemented widely . Alcohol misuse is implicated in unsafe sex and sexually transmitted infections and is common in clients of sexual health services . Our aims were to assess feasibility , acceptability and effectiveness of screening and brief intervention for risky alcohol consumption by a nurse in a sexual health clinic . Methods : Patients completed the AUDIT question naire on h and held computers . Those scoring ⩾8 on AUDIT were asked to participate in the study and the 3 months ’ follow-up and were r and omised to intervention or control groups . The Drink-less package ( based on WHO vali date d methods ) was used to implement the brief intervention by a trained registered nurse . Results : Of 519 ( 87 % ) who completed screening , 204 ( 39 % ) scored ⩾8 on AUDIT ( eligible ) , 184 agreed to follow-up and 133 completed it . At follow-up , both groups showed significant reductions in AUDIT scores . Mean scores decreased from 13.7 to 11.5 ( control group ) and 14.0 to 10.7 ( intervention group ) ; most ( 94 % ) recalled the intervention and 62 % reported reducing drinking compared with 47 % of controls ( p<0.001 ) . The nurse screening and intervention process was reported acceptable by 74 % of patients at follow-up and a majority ( 71 % ) of staff . Conclusions : Screening and brief intervention in a sexual health clinic for risky alcohol consumption is feasible , acceptable and effective in producing significant reductions in drinking as measured by AUDIT . Both intervention and control groups decreased consumption , suggesting that screening alone is sufficient to influence behaviour . Further study of brief intervention in this setting is appropriate OBJECTIVE To identify predictors of smoking cessation success or failure with and without transdermal nicotine patch treatment . DESIGN Two independent r and omized , double-blind , placebo-controlled studies using the nicotine patch assessing outcome at the end of treatment and at 6-month follow-up ; each study used a different mode of adjuvant counseling . PATIENTS Subjects were daily smokers ( > or = 15 cigarettes per day ) , aged 21 to 65 years with expired air carbon monoxide levels of at least 10 ppm , and motivated to quit . Eighty-eight subjects participated in study 1 , and 112 subjects participated in study 2 . INTERVENTION Study 1 consisted of 8 weeks of 22-mg nicotine patch therapy with intensive group counseling . Study 2 consisted of 4 weeks of 22-mg nicotine patch therapy and 2 weeks of 11-mg nicotine patch therapy with brief individual counseling . MAIN OUTCOME MEASURES The prediction of smoking cessation ( at end of treatment and after 6 months ) based on pretreatment and intratreatment measures in smokers using active or placebo nicotine patches . RESULTS Pretreatment markers , such as the Fagerstrom Tolerance Question naire score , number of cigarettes smoked per day , years smoked , expired air carbon monoxide level , or baseline blood nicotine and cotinine levels , showed no consistent relationship with successful smoking cessation across both studies . Of the intratreatment markers examined , withdrawal severity and nicotine replacement levels also were not consistently predictive of cessation success . However , any smoking during the second week of treatment was a consistent and powerful predictor of failure at the end of treatment and after 6 months . Among active nicotine patch patients who smoked at all during week 2 after quitting , 83 % and 97 % ( studies 1 and 2 , respectively ) were smoking at 6-month follow-up . Conversely , abstinence during the second week of treatment predicted successful smoking cessation . Among active nicotine patch patients who were totally abstinent during week 2 after quitting , 46 % and 41 % ( studies 1 and 2 , respectively ) were abstinent at 6-month follow-up . Of all nicotine patch patients in both studies who were smoking at 6-month follow-up , 74 % began smoking during week 1 or 2 . Among all placebo patch patients who were smoking at 6-month follow-up , 86 % began smoking during week 1 or 2 . CONCLUSIONS Smoking status ( abstinent or smoking ) during the first 2 weeks of nicotine patch therapy , particularly week 2 , was highly correlated with clinical outcome and can serve as a powerful predictor of smoking cessation . Early smoking behavior also predicted outcome among placebo patch users . Traditional measures of dependence are not consistently predictive of cessation success . Clinicians are advised to emphasize the importance of total abstinence after a quit attempt and to follow-up with patients within the first 2 weeks of quitting ; smoking during this critical time should be assessed and treatment may be altered as appropriate 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 Output:	Extended intervention when compared with brief intervention was associated with a non-significantly greater reduction in alcohol consumption ( mean difference = -28 , 95%CI : -62 to 6 grams/week , I2 = 0 % ) AUTHORS ' CONCLUSIONS Brief interventions consistently produced reductions in alcohol consumption . When data were available by gender , the effect was clear in men at one year of follow up , but unproven in women . Longer duration of counselling probably has little additional effect .
MS2910	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: In this proof-of-concept , open-label , phase 2 study , patients with relapsed/refractory multiple myeloma ( RRMM ) received elotuzumab with bortezomib and dexamethasone ( EBd ) or bortezomib and dexamethasone ( Bd ) until disease progression/unacceptable toxicity . Primary endpoint was progression-free survival ( PFS ) ; secondary /exploratory endpoints included overall response rate ( ORR ) and overall survival ( OS ) . Two-sided 0.30 significance level was specified ( 80 % power , 103 events ) to detect hazard ratio ( HR ) of 0.69 . Efficacy and safety analyses were performed on all r and omized patients and all treated patients , respectively . Of 152 r and omized patients ( 77 EBd , 75 Bd ) , 150 were treated ( 75 EBd , 75 Bd ) . PFS was greater with EBd vs Bd ( HR , 0.72 ; 70 % confidence interval [ CI ] , 0.59 - 0.88 ; stratified log-rank P = .09 ) ; median PFS was longer with EBd ( 9.7 months ) vs Bd ( 6.9 months ) . In an up date d analysis , EBd-treated patients homozygous for the high-affinity FcγRIIIa allele had median PFS of 22.3 months vs 9.8 months in EBd-treated patients homozygous for the low-affinity allele . ORR was 66 % ( EBd ) vs 63 % ( Bd ) . Very good partial response or better occurred in 36 % of patients ( EBd ) vs 27 % ( Bd ) . Early OS results , based on 40 deaths , revealed an HR of 0.61 ( 70 % CI , 0.43 - 0.85 ) . To date , 60 deaths have occurred ( 28 EBd , 32 Bd ) . No additional clinical ly significant adverse events occurred with EBd vs Bd . Grade 1/2 infusion reaction rate was low ( 5 % EBd ) and mitigated with premedication . In patients with RRMM , elotuzumab , an immunostimulatory antibody , appears to provide clinical benefit without added clinical ly significant toxicity when combined with Bd vs Bd alone . Registered to Clinical Trials.gov as NCT01478048 PURPOSE This phase I study evaluated elotuzumab , lenalidomide , and dexamethasone in patients with relapsed or refractory multiple myeloma ( MM ) . PATIENTS AND METHODS Three cohorts were enrolled and treated with elotuzumab ( 5.0 , 10 , or 20 mg/kg intravenously ) on days 1 , 8 , 15 , and 22 of a 28-day cycle in the first two cycles , and days 1 and 15 of each subsequent cycle ; lenalidomide 25 mg orally [ PO ] on days 1 to 21 ; and dexamethasone 40 mg PO weekly . Dose-limiting toxicities ( DLTs ) were assessed during cycle 1 of each cohort , and clinical responses were evaluated during each cycle . The first five patients received up to six cycles of therapy ; subsequent patients were treated until disease progression . RESULTS Twenty-nine patients with advanced MM and a median of three prior MM therapies were enrolled ; 28 patients were treated , three each in the 5.0-mg/kg and 10-mg/kg cohorts and 22 in the 20-mg/kg cohort . No DLTs were observed up to the maximum proposed dose of 20 mg/kg . The most frequent grade 3 to 4 toxicities were neutropenia ( 36 % ) and thrombocytopenia ( 21 % ) . Two patients experienced a serious infusion reaction ( one grade 4 anaphylactic reaction and one grade 3 stridor ) during the first treatment cycle . Objective responses were obtained in 82 % ( 23 of 28 ) of treated patients . After a median of 16.4 months follow-up , the median time to progression was not reached for patients in the 20-mg/kg cohort who were treated until disease progression . CONCLUSION The combination of elotuzumab , lenalidomide , and low-dose dexamethasone was generally well tolerated and showed encouraging response rates in patients with relapsed or refractory MM Daratumumab , a human CD38 immunoglobulin G1 kappa ( IgG1κ ) monoclonal antibody , has activity as monotherapy in multiple myeloma ( MM ) . This phase 1/2 study investigated daratumumab plus lenalidomide/dexamethasone in refractory and relapsed/refractory MM . Part 1 ( dose escalation ) evaluated 4 daratumumab doses plus lenalidomide ( 25 mg/day orally on days 1 - 21 of each cycle ) and dexamethasone ( 40 mg/week ) . Part 2 ( dose expansion ) evaluated daratumumab at the recommended phase 2 dose ( RP2D ) plus lenalidomide/dexamethasone . Safety , efficacy , pharmacokinetics , immunogenicity , and accelerated daratumumab infusions were studied . In part 1 ( 13 patients ) , no dose-limiting toxicities were observed , and 16 mg/kg was selected as the R2PD . In part 2 ( 32 patients ) , median time since diagnosis was 3.2 years , with a median of 2 prior therapies ( range , 1 - 3 prior therapies ) , including proteasome inhibitors ( 91 % ) , alkylating agents ( 91 % ) , autologous stem cell transplantation ( 78 % ) , thalidomide ( 44 % ) , and lenalidomide ( 34 % ) ; 22 % of patients were refractory to the last line of therapy . Grade 3 to 4 adverse events ( ≥5 % ) included neutropenia , thrombocytopenia , and anemia . In part 2 , infusion-related reactions ( IRRs ) occurred in 18 patients ( 56 % ) ; most were grade ≤2 ( grade 3 , 6.3 % ) . IRRs predominantly occurred during first infusions and were more common during accelerated infusions . In part 2 ( median follow-up of 15.6 months ) , overall response rate was 81 % , with 8 stringent complete responses ( 25 % ) , 3 complete responses ( 9 % ) , and 9 very good partial responses ( 28 % ) . Eighteen-month progression-free and overall survival rates were 72 % ( 95 % confidence interval , 51.7 - 85.0 ) and 90 % ( 95 % confidence interval , 73.1 - 96.8 ) , respectively . Daratumumab plus lenalidomide/dexamethasone result ed in rapid , deep , durable responses . The combination was well tolerated and consistent with the safety profiles observed with lenalidomide/dexamethasone or daratumumab monotherapy . This trial was registered at www . clinical trials.gov as # NCT01615029 BACKGROUND Few effective treatments exist for patients with refractory or relapsed and refractory multiple myeloma not responding to treatment with bortezomib and lenalidomide . Pomalidomide alone has shown limited efficacy in patients with relapsed multiple myeloma , but synergistic effects have been noted when combined with dexamethasone . We compared the efficacy and safety of pomalidomide plus low-dose dexamethasone with high-dose dexamethasone alone in these patients . METHODS This multicentre , open-label , r and omised phase 3 trial was undertaken in Australia , Canada , Europe , Russia , and the USA . Patients were eligible if they had been diagnosed with refractory or relapsed and refractory multiple myeloma , and had failed at least two previous treatments of bortezomib and lenalidomide . They were assigned in a 2:1 ratio with a vali date d interactive voice and internet response system to either 28 day cycles of pomalidomide ( 4 mg/day on days 1 - 21 , orally ) plus low-dose dexamethasone ( 40 mg/day on days 1 , 8 , 15 , and 22 , orally ) or high-dose dexamethasone ( 40 mg/day on days 1 - 4 , 9 - 12 , and 17 - 20 , orally ) until disease progression or unacceptable toxicity . Stratification factors were age ( ≤75 years vs > 75 years ) , disease population ( refractory vs relapsed and refractory vs bortezomib intolerant ) , and number of previous treatments ( two vs more than two ) . The primary endpoint was progression-free survival ( PFS ) . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT01311687 , and with EudraCT , number 2010 - 019820 - 30 . FINDINGS The accrual for the study has been completed and the analyses are presented . 302 patients were r and omly assigned to receive pomalidomide plus low-dose dexamethasone and 153 high-dose dexamethasone . After a median follow-up of 10·0 months ( IQR 7·2 - 13·2 ) , median PFS with pomalidomide plus low-dose dexamethasone was 4·0 months ( 95 % CI 3·6 - 4·7 ) versus 1·9 months ( 1·9 - 2·2 ) with high-dose dexamethasone ( hazard ratio 0·48 [ 95 % CI 0·39 - 0·60 ] ; p<0·0001 ) . The most common grade 3 - 4 haematological adverse events in the pomalidomide plus low-dose dexamethasone and high-dose dexamethasone groups were neutropenia ( 143 [ 48 % ] of 300 vs 24 [ 16 % ] of 150 , respectively ) , anaemia ( 99 [ 33 % ] vs 55 [ 37 % ] , respectively ) , and thrombocytopenia ( 67 [ 22 % ] vs 39 [ 26 % ] , respectively ) . Grade 3 - 4 non-haematological adverse events in the pomalidomide plus low-dose dexamethasone and high-dose dexamethasone groups included pneumonia ( 38 [ 13 % ] vs 12 [ 8 % ] , respectively ) , bone pain ( 21 [ 7 % ] vs seven [ 5 % ] , respectively ) , and fatigue ( 16 [ 5 % ] vs nine [ 6 % ] , respectively ) . There were 11 ( 4 % ) treatment-related adverse events leading to death in the pomalidomide plus low-dose dexamethasone group and seven ( 5 % ) in the high-dose dexamethasone group . INTERPRETATION Pomalidomide plus low-dose dexamethasone , an oral regimen , could be considered a new treatment option in patients with refractory or relapsed and refractory multiple myeloma . FUNDING Celgene Corporation BACKGROUND Daratumumab showed promising efficacy alone and with lenalidomide and dexamethasone in a phase 1 - 2 study involving patients with relapsed or refractory multiple myeloma . METHODS In this phase 3 trial , we r and omly assigned 569 patients with multiple myeloma who had received one or more previous lines of therapy to receive lenalidomide and dexamethasone either alone ( control group ) or in combination with daratumumab ( daratumumab group ) . The primary end point was progression-free survival . RESULTS At a median follow-up of 13.5 months in a protocol -specified interim analysis , 169 events of disease progression or death were observed ( in 53 of 286 patients [ 18.5 % ] in the daratumumab group vs. 116 of 283 [ 41.0 % ] in the control group ; hazard ratio , 0.37 ; 95 % confidence interval [ CI ] , 0.27 to 0.52 ; P<0.001 by stratified log-rank test ) . The Kaplan-Meier rate of progression-free survival at 12 months was 83.2 % ( 95 % CI , 78.3 to 87.2 ) in the daratumumab group , as compared with 60.1 % ( 95 % CI , 54.0 to 65.7 ) in the control group . A significantly higher rate of overall response was observed in the daratumumab group than in the control group ( 92.9 % vs. 76.4 % , P<0.001 ) , as was a higher rate of complete response or better ( 43.1 % vs. 19.2 % , P<0.001 ) . In the daratumumab group , 22.4 % of the patients had results below the threshold for minimal residual disease ( 1 tumor cell per 105 white cells ) , as compared with 4.6 % of those in the control group ( P<0.001 ) ; results below the threshold for minimal residual disease were associated with improved outcomes . The most common adverse events of grade 3 or 4 during treatment were neutropenia ( in 51.9 % of the patients Output:	Additionally , the efficacy of triplet regimens was superior to that of single or doublet regimens . The same trend was observed in a subgroup analysis of daratumumab and elotuzumab . Elotuzumab and daratumumab improved the ORR , at least VGPR , and PFS compared to non-mAb-based regimens . In a pooled analysis , both mAbs had promising efficacy and safety profiles , particularly in triplet regimens . The same trend was observed in daratumumab- and elotuzumab-based regimens . Daratumumab triplet therapy ( daratumumab , lenalidomide , and dexamethasone ) was superior to other triplet regimens for the treatment of RRMM , and daratumumab monotherapy was more effective than either single agent in heavily pretreated MM patients , suggesting CD38 is an effective target for treatment of RRMM .
MS2911	*TASK* the task is to summarize an input biomedical literature in six sentences *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 evidence that exercise intervention is effective for treatment of chronic low back pain comes from trials that are not placebo-controlled . Objective The purpose of this study was to investigate the efficacy of motor control exercise for people with chronic low back pain . Design This was a r and omized , placebo-controlled trial . Setting The study was conducted in an outpatient physical therapy department in Australia . Patients The participants were 154 patients with chronic low back pain of more than 12 weeks ’ duration . Intervention Twelve sessions of motor control exercise ( ie , exercises design ed to improve function of specific muscles of the low back region and the control of posture and movement ) or placebo ( ie , detuned ultrasound therapy and detuned short-wave therapy ) were conducted over 8 weeks . Measurements Primary outcomes were pain intensity , activity ( measured by the Patient-Specific Functional Scale ) , and patient 's global impression of recovery measured at 2 months . Secondary outcomes were pain ; activity ( measured by the Patient-Specific Functional Scale ) ; patient 's global impression of recovery measured at 6 and 12 months ; activity limitation ( measured by the Rol and -Morris Disability Question naire ) at 2 , 6 , and 12 months ; and risk of persistent or recurrent pain at 12 months . Results The exercise intervention improved activity and patient 's global impression of recovery but did not clearly reduce pain at 2 months . The mean effect of exercise on activity ( measured by the Patient-Specific Functional Scale ) was 1.1 points ( 95 % confidence interval [CI]=0.3 to 1.8 ) , the mean effect on global impression of recovery was 1.5 points ( 95 % CI=0.4 to 2.5 ) , and the mean effect on pain was 0.9 points ( 95 % CI=−0.01 to 1.8 ) , all measured on 11-point scales . Secondary outcomes also favored motor control exercise . Limitation Clinicians could not be blinded to the intervention they provided . Conclusions Motor control exercise produced short-term improvements in global impression of recovery and activity , but not pain , for people with chronic low back pain . Most of the effects observed in the short term were maintained at the 6- and 12-month follow-ups OBJECTIVE To compare the effects of 4 months of isolated lumbar resistance exercise and total body resistance exercise on walking performance in obese , older adults with chronic low back pain . A secondary analysis examined whether responsiveness to training modulated walking improvement . DESIGN R and omized , controlled trial . SETTING Research laboratory affiliated with tertiary care facility . METHODS AND INTERVENTION Participants ( N = 49 ; 60 - 85 years ) were r and omized into a 4-month resistance exercise intervention ( TOTRX ) , lumbar extensor exercise intervention ( LEXT ) , or a control group ( CON ) . MAIN OUTCOME MEASUREMENTS Walking performance , maximal low back strength and leg strength , and average resting and low back pain severity score ( from an 11-point numerical pain rating scale ; NRSpain ) were collected at baseline and month 4 . RESULTS The TOTRX and LEXT improved lumbar extensor strength relative to CON , and the TOTRX ( P < .05 ) . NRSpain scores at month 4 were lowest in the TOTRX group compared with the LEXT and CON groups , respectively ( 2.0 ± 1.7 points vs 3.7 ± 2.6 points and 4.6 ± 2.4 points ; P < .006 ) . A total of 53 % and 67 % of participants in the TOTRX and LEXT groups were responders who made lumbar extensor strength gains that achieved ≥20 % greater than baseline values . Although the TOTRX demonstrated the greatest improvement in walking endurance among the intervention groups , this did not reach significance ( 10.1 ± 12.2 % improvement in TOTRX vs 7.4 ± 30.0 % LEXT and -1.7 ± 17.4 % CON ; P = .11 ) . Gait speed increased most in the TOTRX ( 9.0 ± 13.5 % ) compared with the LEXT and CON groups ( P < .05 ) . The change in lumbar extensor strength explained 10.6 % of the variance of the regression model for the change in walking endurance ( P = .024 ) . CONCLUSIONS The use of LEXT and TOTRX produced similar modest improvements in patients ' walking endurance . Lumbar extensor strength gain compared with leg strength gain is a moderate but important contributor to walking endurance in obese older adults with chronic low back pain . Responders to resistance exercise programs ( event those with only lumbar extension exercise ) who make at least a 20 % improvement in strength can expect better improvement in walking endurance than those who do not achieve this strength improvement Background The treatment of non-specific chronic low back pain is often based on three different models regarding the development and maintenance of pain and especially functional limitations : the deconditioning model , the cognitive behavioral model and the biopsychosocial model . There is evidence that rehabilitation of patients with chronic low back pain is more effective than no treatment , but information is lacking about the differential effectiveness of different kinds of rehabilitation . A direct comparison of a physical , a cognitive-behavioral treatment and a combination of both has never been carried out so far . Methods The effectiveness of active physical , cognitive-behavioral and combined treatment for chronic non-specific low back pain compared with a waiting list control group was determined by performing a r and omized controlled trial in three rehabilitation centers . Two hundred and twenty three patients were r and omized , using concealed block r and omization to one of the following treatments , which they attended three times a week for 10 weeks : Active Physical Treatment ( APT ) , Cognitive-Behavioral Treatment ( CBT ) , Combined Treatment of APT and CBT ( CT ) , or Waiting List ( WL ) . The outcome variables were self-reported functional limitations , patient 's main complaints , pain , mood , self-rated treatment effectiveness , treatment satisfaction and physical performance including walking , st and ing up , reaching forward , stair climbing and lifting . Assessment s were carried out by blinded research assistants at baseline and immediately post-treatment . The data were analyzed using the intention-to-treat principle . Results For 212 patients , data were available for analysis . After treatment , significant reductions were observed in functional limitations , patient 's main complaints and pain intensity for all three active treatments compared to the WL . Also , the self-rated treatment effectiveness and satisfaction appeared to be higher in the three active treatments . Several physical performance tasks improved in APT and CT but not in CBT . No clinical ly relevant differences were found between the CT and APT , or between CT and CBT . Conclusion All three active treatments were effective in comparison to no treatment , but no clinical ly relevant differences between the combined and the single component treatments were found Objectives Although motor control exercises have been shown to be effective in the management of low back pain ( LBP ) the mechanism of action is unclear . The current study investigated the relationship between the ability to recruit transversus abdominis and clinical outcomes of participants in a clinical trial . Methods Ultrasonography was used to assess the ability to recruit transversus abdominis in a nested design : a sample of 34 participants with chronic LBP was recruited from participants in a r and omised controlled trial comparing the efficacy of motor control exercise , general exercise and spinal manipulative therapy . Perceived recovery , function , disability and pain were also assessed . Results Participants with chronic LBP receiving motor control exercise had a greater improvement in recruitment of transversus abdominis ( 7.8 % ) than participants receiving general exercise ( 4.9 % reduction ) or spinal manipulative therapy ( 3.7 % reduction ) . The effect of motor control exercise on pain reduction was greater in participants who had a poor ability to recruit transversus abdominis at baseline . There was a significant , moderate correlation between improved recruitment of transversus abdominis and a reduction in disability ( r = −0.35 ; 95 % CI 0.02 to 0.62 ) . Conclusion These data provide some support for the hypothesised mechanism of action of motor control exercise and suggest that the treatment may be more effective in those with a poor ability to recruit transversus abdominis OBJECTIVE To determine if the use of an isokinetic device for trunk exercise is more effective than st and ard physiotherapy in promoting motor disinhibition for patients with chronic low back pain . POPULATION chronic low back pain out patients who are treated in a Rheumatology or PM & R unit within an academic hospital . METHODOLOGY This is a prospect i ve , controlled , r and omized study , with two groups of treatment : one treated with isokinetic techniques and the other with st and ard physiotherapy , six sessions for each treatment during 2 weeks . Outcome measures include pain ( VSA ) , trunk mobility ( Schöber index , distance from fingers to floor ) , muscle extensibility and muscle strength ( Biering-Sorensen and Shirado-Ito test ) , and functional capacity ( Quebec scale ) . RESULTS Seventeen subjects were enrolled . The results suggest that both isokinetic exercise and physiotherapy result in improved range of motion , extensibility , muscle strength , and pain , without any significant superiority of one technique over the other . However , each technique has specific advantage . DISCUSSION Despite method ologic limitations , this study shows that isokinetic exercise is not better than physiotherapy in reversing motor inhibition in chronic low back pain . Our results are consistent with those of other studies in the literature , with regard to the absence of established overall superiority of one exercise technique or program over the other in this population , and with regard to partial benefits of specific exercise techniques . CONCLUSION The non-specific benefit of one technique indicates that further studies are needed to evaluate the benefit of combining exercise techniques in chronic low back pain , in order to address the multiple factors involved in this pathology 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 OBJECTIVE To develop a clinical prediction rule to predict treatment response to a stabilization exercise program for patients with low back pain ( LBP ) . DESIGN A prospect i ve , cohort study of patients with nonradicular LBP referred to physical therapy ( PT ) . SETTING Outpatient PT clinics . PARTICIPANTS Fifty-four patients with nonradicular LBP . INTERVENTION A st and ardized stabilization exercise program . MAIN OUTCOME MEASURE Treatment response ( success or failure ) was categorized based on changes in the Oswestry Disability Question naire scores after 8 weeks . RESULTS Eighteen subjects were categorized as treatment successes , 15 as treatment failures , and 21 as somewhat improved . After using regression analyses to determine the association between st and ardized examination variables and treatment response status , preliminary clinical prediction rules were developed for predicting success ( positive likelihood ratio [ LR ] , 4.0 ) and failure ( negative LR , .18 ) . The most important variables were age , straight-leg raise , prone instability test , aberrant motions , lumbar hypermobility , and fear-avoidance beliefs . CONCLUSIONS It appears that the response to a stabilization exercise program in patients with LBP can be predicted from variables collected from the clinical examination . The prediction rules could be used to determine whether patients with LBP are likely to benefit from stabilization exercises The application of single motor unit biofeedback training ( SMUBT ) techniques was compared to traditional therapies in treating chronic low back pain ( CLBP ) . Thirty-six volunteers ( who experienced daily pain for 7 years in the T8 to S1 area ) were r and omly assigned to one of three treatments ; SMUBT , relaxation training , or an educational program . The pain level and electromyographic activity of all subjects were assessed by a person blind to the treatment ; before , immediately after , and 90 days after treatment . The SMUBT group reported immediately decreased pain which was maintained at 90 days , the relaxation group showed no changes , while the education group reported decreased pain at 90 days . The EMG results showed decreased amplitude and bilateral differences for the SMUBT and education groups . A 4-year follow-up revealed the SMUBT group remained symptom free . Implication s and discussion of the results concludes the paper Context Yoga combines exercise with achieving a state of mental focus through breath Output:	Conclusions : Our results found a beneficial effect for strength/resistance and coordination/stabilisation exercise programs over other interventions in the treatment of chronic low back pain and that cardiorespiratory and combined exercise programs are ineffective
MS2912	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background and Purpose — Despite the importance of exercise training in mitigating cardiovascular risk , the development of exercise programs for people poststroke has been limited by lack of feasibility data concerning cardiopulmonary exercise testing ( CPET ) to inform the exercise prescription . Therefore , we examined the feasibility of CPETs for developing an exercise prescription in people ≥3 months poststroke . Methods — CPET results from 98 consecutively enrolled patients poststroke with motor impairments and 98 age- and sex-matched patients with coronary artery disease were examined at baseline and after 6 months of exercise training . Results — The proportion of patients with stroke and coronary artery disease attaining an intensity sufficient for prescribing exercise at baseline was 68.4 % versus 82.7 % , respectively ( P=0.02 ) and 84.7 % versus 83.8 % ( P=0.9 ) at 6 months . Women were less likely than men poststroke to achieve a sufficient intensity at baseline ( 40 % versus 80.9 % , P<0.001 ) but not at 6 months ( 78.3 % versus 87.1 , P=0.3 ) . A clinical ly relevant abnormality occurred in 11.2 % of stroke and 12.2 % of patients with coronary artery disease on baseline CPETs ( P=0.8 ) and 10.6 % of stroke and 5.9 % of patients with coronary artery disease on the 6-month CPET ( P=0.4 ) . No serious cardiovascular events occurred during 349 CPETs . Conclusions — Most patients after stroke achieved a level of exertion during the CPET sufficient to inform an exercise prescription . At least 1 of 10 patients poststroke developed a clinical ly relevant abnormality on baseline and postprogram CPETs with no serious cardiovascular events . These data support the feasibility and safety of CPETs for prescribing exercise poststroke . Strategies to improve use of baseline CPETs for women poststroke require further investigation This study evaluated the feasibility , safety , and findings from a protocol for exercise-bicycle ergometry in subacute-stroke survivors . Of 117 eligible c and i date s , 14 could not perform the test and 3 discontinued because of cardiac safety criteria . In the 100 completed tests , peak heart rate was 116 + /- 19.1 beats/min ; peak VO(2 ) was 11.4 + /- 3.7 ml x kg x min(-1 ) , peak METs were 3.3 + /- 0.91 , exercise duration was 5.1 + /- 2.84 min , and Borg score was 14 + /- 2.6 . Among 71 tests , anaerobic threshold was achieved in 3.0 + /- 1.7 min with a VO(2 ) of 8.6 + /- 1.7 ml x kg x min(-1 ) . After screening , this protocol is feasible and safe in subacute-stroke survivors with mild to moderate deficits . These stroke survivors have severely limited functional exercise capacity . Research and clinical practice in stroke rehabilitation should incorporate more comprehensive evaluation and treatment of endurance limitations Abstract Purpose : The majority of post-stroke individuals suffer from low exercise capacity as a secondary reaction to immobility . The aim of this study was to prove the concept of feedback-controlled robotics-assisted treadmill exercise ( RATE ) to assess aerobic capacity and guide cardiovascular exercise in severely impaired individuals early after stroke . Method : Subjects underwent constant load and incremental exercise testing using a human-in-the-loop feedback system within a robotics-assisted exoskeleton ( Lokomat , Hocoma AG , CH ) . Inclusion criteria were : stroke onset ≤8 weeks , stable medical condition , non-ambulatory status , moderate motor control of the lower limbs and appropriate cognitive function . Outcome measures included oxygen uptake kinetics , peak oxygen uptake ( VO2peak ) , gas exchange threshold ( GET ) , peak heart rate ( HRpeak ) , peak work rate ( Ppeak ) and accuracy of reaching target work rate ( P-RMSE ) . Results : Three subjects ( 18–42 d post-stroke ) were included . Oxygen uptake kinetics during constant load ranged from 42.0 to 60.2 s. Incremental exercise testing showed : VO2peak range 19.7–28.8 ml/min/kg , GET range 11.6–12.7 ml/min/kg , and HRpeak range 115–161 bpm . Ppeak range was 55.2–110.9 W and P-RMSE range was 3.8–7.5 W. Conclusions : The concept of feedback-controlled RATE for assessment of aerobic capacity and guidance of cardiovascular exercise is feasible . Further research is warranted to vali date the method on a larger scale . Implication s for Rehabilitation Aerobic capacity is seriously reduced in post-stroke individuals as a secondary reaction to immobility . Robotics-assisted walking devices may have substantial clinical relevance regarding assessment and improvement of aerobic capacity early after stroke . Feedback-controlled robotics-assisted treadmill exercise represents a new concept for cardiovascular assessment and intervention protocol s for severely impaired individuals BACKGROUND AND PURPOSE Rehabilitation care after stroke is highly variable and increasingly shorter in duration . The effect of therapeutic exercise on impairments and functional limitations after stroke is not clear . The objective of this study was to determine whether a structured , progressive , physiologically based exercise program for subacute stroke produces gains greater than those attributable to spontaneous recovery and usual care . METHODS This r and omized , controlled , single-blind clinical trial was conducted in a metropolitan area and 17 participating healthcare institutions . We included persons with stroke who were living in the community . One hundred patients ( mean age , 70 years ; mean Orpington score , 3.4 ) consented and were r and omized from a screened sample of 582 . Ninety-two subjects completed the trial . Intervention was a structured , progressive , physiologically based , therapist-supervised , in-home program of thirty-six 90-minute sessions over 12 weeks targeting flexibility , strength , balance , endurance , and upper-extremity function . Main outcome measures were postintervention strength ( ankle and knee isometric peak torque , grip strength ) , upper- and lower-extremity motor control ( Fugl Meyer ) , balance ( Berg and functional reach ) , endurance ( peak aerobic capacity and exercise duration ) , upper-extremity function ( Wolf Motor Function Test ) , and mobility ( timed 10-m walk and 6-minute walk distance ) . RESULTS In the intention-to-treat multivariate analysis of variance testing the overall effect , the intervention produced greater gains than usual care ( Wilk 's lambda=0.64 , P=0.0056 ) . Both intervention and usual care groups improved in strength , balance , upper- and lower-extremity motor control , upper-extremity function , and gait velocity . Gains for the intervention group exceeded those in the usual care group in balance , endurance , peak aerobic capacity , and mobility . Upper-extremity gains exceeded those in the usual care group only in patients with higher baseline function . CONCLUSIONS This structured , progressive program of therapeutic exercise in persons who had completed acute rehabilitation services produced gains in endurance , balance , and mobility beyond those attributable to spontaneous recovery and usual care Background The test – retest reliability for multiple cardiopulmonary exercise test ( CPX ) variables has not been compared in a single study and the influence of different diseases on test – retest reliability has not been examined . We investigated different measures of test – retest reliability for multiple variables and compared them by category of cardiac or respiratory disease . Methods Patients with chronic obstructive airways disease ( n = 24 ) , heart failure ( n = 43 ) , or severe mitral valve disease ( n = 26 ) were recruited into a prospect i ve study . Each patient underwent two bicycle ergometer tests ; the first , a familiarization test , with a 10 W/min ramp , and the second a personalized ramp based on the results of the familiarization test to elicit maximal effort within 8–10 min . Intraclass correlation coefficients ( ICC ) and coefficients of variation between the two tests were calculated . Influence of potential modifiers was assessed using repeated measures analysis of variance . Results Peak VO2 ( ICC 0.95 , 95 % CI 0.94–0.97 ) , oxygen uptake efficiency slope ( ICC 0.93 , 95 % CI 0.90–0.95 ) , O2 pulse ( ICC 0.96 , 95 % CI 0.94–0.97 ) , and the VE/VCO2 ratio at the nadir ( ICC 0.92 , 95 % CI 0.89–0.95 ) all showed excellent test – retest reliability , with within-subject coefficients of variation < 0.12 . VO2 at the anaerobic threshold ( ICC 0.84 , 95 % CI 0.78–0.89 ) and the VE/VCO2 slope ( ICC 0.88 , 95 % CI 0.79–0.93 ) showed good test – retest reliability , although inferior to peak VO2 . Age , gender , body mass index , disease aetiology , protocol change , and intertest interval did not affect the reliability of most variables . Conclusions CPX showed high test – retest reliability ; certain variables such as peak VO2 and oxygen uptake efficiency slope outperform others . These results identify which variables are most suitable for serial testing of patients with three common disease aetiologies owing to their superior reproducibility Objectives For the measurement of patient-reported outcomes , such as ( health-related ) quality of life , often many measurement instruments exist that intend to measure the same construct . To facilitate instrument selection , our aim was to develop a highly sensitive search filter for finding studies on measurement properties of measurement instruments in PubMed and a more precise search filter that needs less abstract s to be screened , but at a higher risk of missing relevant studies . Methods A r and om sample of 10,000 PubMed records ( 01 - 01 - 1990 to 31 - 12 - 2006 ) was used as a gold st and ard . Studies on measurement properties were identified using an exclusion filter and h and search ing . Search terms were selected from the relevant records in the gold st and ard as well as from 100 systematic review s of measurement properties and combined based on sensitivity and precision . The performance of the filters was tested in the gold st and ard as well as in two validation sets , by calculating sensitivity , precision , specificity , and number needed to read . Results We identified 116 studies on measurement properties in the gold st and ard . The sensitive search filter was able to retrieve 113 of these 116 studies ( sensitivity 97.4 % , precision 4.4 % ) . The precise search filter had a sensitivity of 93.1 % and a precision of 9.4 % . Both filters performed very well in the validation sets . Conclusion The use of these search filters will contribute to evidence -based selection of measurement instruments in all medical fields The assessment of functional capacity reflects the ability to perform activities of daily living that require sustained aerobic metabolism . The integrated efforts and health of the pulmonary , cardiovascular , and skeletal muscle systems dictate an individual ’s functional capacity . Numerous investigations have demonstrated that the assessment of functional capacity provides important diagnostic and prognostic information in a wide variety of clinical and research setting s. This scientific statement , an up date of the previously published American Heart Association ( AHA ) document,1 highlights the major clinical and research applications of functional capacity assessment . For a comprehensive review of exercise testing , the reader is referred to the American College of Cardiology (ACC)/AHA Guidelines for Exercise Testing.2,3 Functional capacity is the ability of an individual to perform aerobic work as defined by the maximal oxygen uptake ( Vo2max ) , that is , the product of cardiac output and arteriovenous oxygen ( a−Vo2 ) difference at physical exhaustion , as shown in the following equation : ! [Formula][1 ] Where HR indicates heart rate and SV indicates stroke volume . Because Vo2max typically is achieved by exercise that involves only about half of the total body musculature , it is generally believed that Vo2max is limited by maximal cardiac output rather than peripheral factors.4 Although Vo2max is measured in liters of oxygen per minute , it usually is expressed in milliliters of oxygen per kilogram of body weight per minute to facilitate intersubject comparisons . In addition , functional capacity , particularly when estimated from the work rate achieved rather than directly measured Vo , is frequently expressed in metabolic equivalents ( METs ) , with 1 MET representing the resting energy expenditure ( ≈3.5 mL O2 · kg−1 · min−1 ) . In this instance , functional capacity is commonly expressed clinical ly as a multiple of the resting metabolic rate . Vo2max … [ 1 ] : Background Exercise testing devices for evaluating cardiopulmonary fitness in patients with severe disability after stroke are lacking , but we have adapted a robotics-assisted tilt table ( RATT ) for cardiopulmonary exercise testing ( CPET ) . Using the RATT in a sample of patients after stroke , this study aim ed to investigate test-retest reliability and repeatability of CPET and to prospect ively investigate changes in cardiopulmonary outcomes over a period of four weeks . Methods Stroke patients with all degrees of disability underwent 3 separate CPET sessions : 2 tests at baseline ( TB1 and TB2 ) and 1 test at follow up ( TF ) . TB1 and TB2 were at least 24 h apart . TB2 and TF were 4 weeks apart . A RATT equipped with force sensors in the thigh cuffs , a work rate estimation algorithm and a real-time visual feedback system was used to guide the patients ’ exercise work rate during CPET . Test-retest reliability and repeatability of CP Output:	No judgement could be made on which protocol is " best " for measuring VO2max in persons after stroke due to lack of high- quality studies on the measurement properties of the cardiopulmonary exercise test
MS2913	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The efficacy of artemether and artemether followed by mefloquine was evaluated in 45 pregnant women with drug resistant Plasmodium falciparum malaria during the second and third trimesters . There was prompt clinical response to both treatment regimens . The parasite and fever clearance times and the cure rate were similar in both groups . Except for the correlation between initial parasite density and fever clearance time in the artemether-mefloquine group , there was no correlation between initial parasite density and parasite or fever clearance times in the two groups . Similarly , there was no correlation between parasite and fever clearance . Both treatment regimens were well tolerated . All newborn babies of the participating women were normal at birth . Physical and neurodevelopmental assessment of the newborn babies followed up for a period varying between 6 and 36 months were within normal limits . Artemether alone or with mefloquine are effective and do not produce undue deleterious effects in pregnant patients with drug-resistant falciparum malaria during the second and third trimesters BACKGROUND Adherence to antimalarial drug regimens is improved by simple dosing . If the fixed antimalarial drug combination artemether-lumefantrine ( AL ) could be given once daily , this should improve adherence and thus effectiveness and lower the risk of selecting for resistance . METHODS In an open r and omized study , 43 patients with uncomplicated falciparum malaria were given equivalent doses of AL with 200 ml flavoured milk either as the conventional twice-daily regimen or as a single daily dose for 3 days . The primary end point was a comparison of the areas under the plasma lumefantrine concentration-time curves ( AUC ) . Secondary end points were the day 42 polymerase chain reaction (PCR)-adjusted cure rates and the tolerability profiles . RESULTS Lumefantrine pharmacokinetic profiles were obtained for 36 patients . The AUC((0 - ->infinity ) ) of the once-daily regimen was 30 % lower than that in the conventional regimen ( P = 0.011 ) with a median ( range ) value of 306 ( 114 - 5781 ) microg/ml h , compared with 432 ( 308 - 992 ) microg/ml h. There was no significant difference in the peak plasma concentrations reached . PCR-adjusted cure rate estimates at day 42 of follow-up were 94 % ( 95 % CI : 84 - 100 ) in the six-dose arm and 85 % ( 70 - 100 ) in the three-dose arm ( P = 0.3 ) . CONCLUSION Artemether-lumefantrine efficacy is reduced by once-daily dosing , because absorption of lumefantrine is dose limited . At currently recommended doses , this antimalarial should be given twice daily in a 3-day regimen , with food containing fat Background To date no comparative trials have been done , to our knowledge , of fixed-dose artemisinin combination therapies ( ACTs ) for the treatment of Plasmodium falciparum malaria in pregnancy . Evidence on the safety and efficacy of ACTs in pregnancy is needed as these drugs are being used increasingly throughout the malaria-affected world . The objective of this study was to compare the efficacy , tolerability , and safety of artemether-lumefantrine , the most widely used fixed ACT , with 7 d artesunate monotherapy in the second and third trimesters of pregnancy . Methods and Findings An open-label r and omised controlled trial comparing directly observed treatment with artemether-lumefantrine 3 d ( AL ) or artesunate monotherapy 7 d ( AS7 ) was conducted in Karen women in the border area of northwestern Thail and who had uncomplicated P. falciparum malaria in the second and third trimesters of pregnancy . The primary endpoint was efficacy defined as the P. falciparum PCR-adjusted cure rates assessed at delivery or by day 42 if this occurred later than delivery , as estimated by Kaplan-Meier survival analysis . Infants were assessed at birth and followed until 1 y of life . Blood sampling was performed to characterise the pharmacokinetics of lumefantrine in pregnancy . Both regimens were very well tolerated . The cure rates ( 95 % confidence interval ) for the intention to treat ( ITT ) population were : AS7 89.2 % ( 82.3%–96.1 % ) and AL 82.0 % ( 74.8%–89.3 % ) , p = 0.054 ( ITT ) ; and AS7 89.7 % ( 82.6%–96.8 % ) and AL 81.2 % ( 73.6%–88.8 % ) , p = 0.031 ( per- protocol population ) . One-third of the PCR-confirmed recrudescent cases occurred after 42 d of follow-up . Birth outcomes and infant ( up to age 1 y ) outcomes did not differ significantly between the two groups . The pharmacokinetic study indicated that low concentrations of artemether and lumefantrine were the main contributors to the poor efficacy of AL . Conclusion The current st and ard six-dose artemether-lumefantrine regimen was well tolerated and safe in pregnant Karen women with uncomplicated falciparum malaria , but efficacy was inferior to 7 d artesunate monotherapy and was unsatisfactory for general deployment in this geographic area . Reduced efficacy probably results from low drug concentrations in later pregnancy . A longer or more frequent AL dose regimen may be needed to treat pregnant women effectively and should now be evaluated . Parasitological endpoints in clinical trials of any antimalarial drug treatment in pregnancy should be extended to delivery or day 42 if it comes later . Trial Registration : Current Controlled Trials IS RCT Background Safety data regarding exposure to artemisinin-based combination therapy in pregnancy are limited . This prospect i ve cohort study conducted in Zambia evaluated the safety of artemether-lumefantrine ( AL ) in pregnant women with malaria . Methods Pregnant women attending antenatal clinics were assigned to groups based on the drug used to treat their most recent malaria episode ( AL vs. sulphadoxine-pyrimethamine , SP ) . Safety was assessed using st and ard and pregnancy-specific parameters . Post-delivery follow-up was six weeks for mothers and 12 months for live births . Primary outcome was perinatal mortality ( stillbirth or neonatal death within seven days after birth ) . Results Data from 1,001 pregnant women ( AL n = 495 ; SP n = 506 ) and 933 newborns ( AL n = 466 ; SP n = 467 ) showed : perinatal mortality ( AL 4.2 % ; SP 5.0 % ) , comprised of early neonatal mortality ( each group 2.3 % ) , stillbirths ( AL 1.9 % ; SP 2.7 % ) ; preterm deliveries ( AL 14.1 % ; SP 17.4 % of foetuses ) ; and gestational age-adjusted low birth weight ( AL 9.0 % ; SP 7.7 % ) . Infant birth defect incidence was 1.8 % AL and 1.6 % SP , excluding umbilical hernia . Abortions prior to antenatal care could not be determined : abortion occurred in 4.5 % of women treated with AL during their first trimester ; none were reported in the 133 women exposed to SP and /or quinine during their first trimester . Overall development ( including neurological assessment ) was similar in both groups . Conclusions These data suggest that exposure to AL in pregnancy , including first trimester , is not associated with particular safety risks in terms of perinatal mortality , malformations , or developmental impairment . However , more data are required on AL use during the first trimester Background . There is some consensus that malaria in pregnancy may negatively affect infant 's mortality and malaria morbidity , but there is less evidence concerning the factors involved . Methods . A total of 1030 Mozambican pregnant women were enrolled in a r and omized , placebo-controlled trial of intermittent preventive treatment with sulfadoxine-pyrimethamine , and their infants were followed up throughout infancy . Overall mortality and malaria morbidity rates were recorded . The association of maternal and fetal risk factors with infant mortality and malaria morbidity was assessed . Results . There were 58 infant deaths among 997 live-born infants . The risk of dying during infancy was increased among infants born to women with acute placental infection ( odds ratio [ OR ] , 5.08 [ 95 % confidence interval ( CI ) , 1.77–14.53 ) ] , parasitemia in cord blood ( OR , 19.31 [ 95 % CI , 4.44–84.02 ] ) , low birth weight ( OR , 2.82 [ 95 % CI , 1.27–6.28 ] ) or prematurity ( OR , 3.19 [ 95 % CI , 1.14–8.95 ] ) . Infants born to women who had clinical malaria during pregnancy ( OR , 1.96 [ 95 % CI , 1.13–3.41 ] ) or acute placental infection ( OR , 4.63 [ 95 % CI , 2.10–10.24 ] ) had an increased risk of clinical malaria during infancy . Conclusions . Malaria infection at the end of pregnancy and maternal clinical malaria negatively impact survival and malaria morbidity in infancy . Effective clinical management and prevention of malaria in pregnancy may improve infant 's health and survival Background Prompt use of an effective anti-malarial drug is essential for controlling malaria and its adverse effects in pregnancy . The World Health Organization recommends an artemisinin-based combination therapy as the first-line treatment of uncomplicated malaria in the second and third trimesters of pregnancy . The study objective was to determine the degree to which presumed episodes of uncomplicated symptomatic malaria in pregnancy were treated with a recommended anti-malarial regimen in a region of Ug and a. Methods Utilizing a population -based r and om sample , we interviewed women living in Jinja , Ug and a who had been pregnant in the past year . Results Self-reported malaria during the index pregnancy was reported among 67 % ( n = 334 ) of the 500 participants . Among the 637 self-reported episodes of malaria , an anti-malarial drug was used for treatment in 85 % of the episodes . Use of a currently recommended treatment in the first trimester was uncommon ( 5.6 % ) . A contraindicated anti-malarial drug ( sulphadoxine-pyrimethamine and /or artemether-lumefantrine ) was involved in 70 % of first trimester episodes . Recommended anti-malarials were used according to the guidelines in only 30.1 % of all second and third trimester episodes . Conclusions Self-reported malaria was extremely common in this population and adherence to treatment guidelines for the management of malaria in pregnancy was poor . Use of artemether-lumefantrine combined with non-recommended anti-malarials was common practice . Overuse of anti-malarial drugs , especially ones that are no longer recommended , undermines malaria control efforts by fueling the spread of drug resistance and delaying appropriate treatment of non-malarial febrile illnesses . Improved diagnostic capacity is essential to ultimately improving the management of malaria-like symptoms during pregnancy and appropriate use of currently available anti-malarials Background Maternal mortality is a major health problem concentrated in re source -poor regions . Accurate data on its causes using rigorous methods is lacking , but is essential to guide policy-makers and health professionals to reduce this intolerable burden . The aim of this study was to accurately describe the causes of maternal death in order to contribute to its reduction , in one of the regions of the world with the highest maternal mortality ratios . Methods and Findings We conducted a prospect i ve study between October 2002 and December 2004 on the causes of maternal death in a tertiary-level referral hospital in Maputo , Mozambique , using complete autopsies with histological examination . HIV detection was done by virologic and serologic tests , and malaria was diagnosed by histological and parasitological examination . During 26 mo there were 179 maternal deaths , of which 139 ( 77.6 % ) had a complete autopsy and formed the basis of this analysis . Of those with test results , 65 women ( 52.8 % ) were HIV-positive . Obstetric complications accounted for 38.2 % of deaths ; haemorrhage was the most frequent cause ( 16.6 % ) . Nonobstetric conditions accounted for 56.1 % of deaths ; HIV/AIDS , pyogenic bronchopneumonia , severe malaria , and pyogenic meningitis were the most common causes ( 12.9 % , 12.2 % , 10.1 % and 7.2 % respectively ) . Mycobacterial infection was found in 12 ( 8.6 % ) maternal deaths . Conclusions In this tertiary hospital in Mozambique , infectious diseases accounted for at least half of all maternal deaths , even though effective treatment is available for the four leading causes , HIV/AIDS , pyogenic bronchopneumonia , severe malaria , and pyogenic meningitis . These observations highlight the need to implement effective and available prevention tools , such as intermittent preventive treatment and insecticide-treated bed-nets for malaria , antiretroviral drugs for HIV/AID Output:	In the second and third trimesters , AL was not associated with increased adverse pregnancy outcomes as compared with quinine or sulphadoxine-pyrimethamine , showed improved tolerability relative to quinine , and its efficacy was non-inferior to quinine . There is evidence to suggest that the pharmacokinetics of anti-malarial drugs may change in pregnancy , although the impact on efficacy and safety needs to be studied further , especially since the majority of studies report high cure rates and adequate tolerability .
MS2914	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Associations between salivary cortisol and maternal psychological distress and well-being were examined prospect ively on 112 women with normally progressing , singleton pregnancies between 24 and 38 weeks gestation . At each of 5 visits , conducted in 3-week intervals , women provided a saliva sample and completed question naires measuring trait anxiety , depressive symptoms , pregnancy-specific hassles and uplifts , and psychological well-being . Maternal salivary cortisol was unrelated to psychological measures with the exception of minor associations detected with measures of anxiety and depressive symptoms between 30 and 32 weeks only . Findings indicate that self-reported maternal psychological distress and well-being are not associated with significant variation in maternal salivary cortisol levels during the second half of gestation . This suggests that studies that measure psychological factors in pregnancy but do not measure maternal cortisol should exercise caution in assuming activation of the maternal hypothalamic – pituitary – adrenal axis is the mechanism through which maternal psychological factors are transduced to the fetus Study goals were to distinguish between maternal risk factors for fetal versus infant mortality , and to identify which maternal characteristics contributed the greatest risk of mortality overall . This case – control retrospective study abstract ed data on more than forty maternal characteristics from 261 prenatal and delivery records : all 26 fetal deaths , all 40 infant deaths and 195 r and omly selected surviving births in a high-mortality Healthy Start community . Bivariate and multivariate analyses were conducted . The fetal-mortality population was significantly more likely than the infant-mortality population to have no insurance ( P = .047 ) , inadequate prenatal care ( P = .039 ) and previous fetal death ( P = .021 ) . Comparing the combined mortality population with the surviving sample , two tiers of risk emerged : Rare-but-lethal risks , including no prenatal care ( P < .001 ) and Child-Protective-Service involvement ( P = .001 ) , and common- and -dangerous risks , including inadequate maternal weight gain ( OR = 13.55 ) , drug or alcohol abuse ( OR = 8.67 ) , obesity ( OR = 2.77 ) and anemia ( OR = 3.61 ) . Both fetal and infant mortality groups must be considered when identifying maternal risks . Inadequate prenatal weight gain , obesity and anemia contribute as much to feto-infant mortality as substance abuse . Public health efforts to improve maternal nutrition and healthy weight should be redoubled This study investigates the relationship between adverse pregnancy outcomes in high-risk African American women in Washington , DC and sociodemographic risk factors , behavioral risk factors , and the most common and interrelated medical conditions occurring during pregnancy : diabetes , hypertension , preeclampsia , and Body Mass Index ( BMI ) . Data are from a r and omized controlled trial conducted in 6 prenatal clinics . Women in their 1st or 2nd trimester were screened for behavioral risks ( smoking , environmental tobacco smoke exposure , depression , and intimate partner violence ) and demographic eligibility . 1,044 were eligible , interviewed and followed through their pregnancies . Classification and Regression Trees ( CART ) methodology was used to : ( 1 ) explore the relationship between medical and behavioral risks ( reported at enrollment ) , sociodemographic factors and pregnancy outcomes ; ( 2 ) identify the relative importance of various predictors of adverse pregnancy outcomes ; and ( 3 ) characterize women at the highest risk of poor pregnancy outcomes . The strongest predictors of poor outcomes were prepregnancy BMI , preconceptional diabetes , employment status , intimate partner violence , and depression . In CART analysis , preeclampsia was the first splitter for low birthweight ; preconceptional diabetes was the first splitter for preterm birth ( PTB ) and neonatal intensive care admission ; BMI was the first splitter for very PTB , large for gestational age , Cesarean section and perinatal death ; employment was the first splitter for miscarriage . Preconceptional factors strongly influence pregnancy outcomes . For many of these women , the high risks they brought into pregnancy were more likely to impact their pregnancy outcomes than events during pregnancy Background Body image satisfaction in pregnancy may have an important influence on maternal biopsychosocial outcomes . Purpose This study aims to examine the mediating influence of trimesters 2 and 3 body image satisfaction on trimesters 2 and 3 depressive symptoms , exercise behavior , and gestational weight gain . Methods Pregnant women ( N = 151 ; mean age = 30 ) prospect ively completed study measures via mail during their 1st , 2nd , and 3rd trimesters . Results As predicted , trimesters 2 and 3 body image satisfaction mediated the relationship between trimester 1 body image satisfaction and trimester 2 depressive symptoms and the relationship between trimester 2 body image satisfaction and trimester 3 depressive symptoms . In contrast to the hypothesis , no mediation was observed for the relationship between body image satisfaction and exercise behavior or gestational weight gain . Conclusions These preliminary findings demonstrate that body image satisfaction is an important psychological determinant of depressive symptoms in pregnancy . Promoting healthy body image may be a non-pharmacological strategy that offers protective effects against depressive symptoms during pregnancy OBJECTIVE To identify and describe dietary patterns in a cohort of pregnant women , and investigate whether dietary patterns during pregnancy are related to postpartum depression ( PPD ) . DESIGN The study uses data from the prospect i ve mother-child cohort ' Rhea ' study . Pregnant women completed an FFQ in mid-pregnancy and the Edinburg Postpartum Depression Scale ( EPDS ) at 8 - 10 weeks postpartum . Dietary patterns during pregnancy ( ' health conscious ' , ' Western ' ) were identified using principal component analysis . Associations between dietary patterns categorized in tertiles and PPD symptoms were investigated by multivariable regression models after adjusting for confounders . SETTING Heraklion , Crete , Greece , 2007 - 2010 . SUBJECTS A total of 529 women , participating in the ' Rhea ' cohort . RESULTS High adherence to a ' health conscious ' diet , characterized by vegetables , fruit , pulses , nuts , dairy products , fish and olive oil , was associated with lower EPDS scores ( highest v. lowest tertile : β-coefficient = -1·75 , P = 0·02 ) . Women in the second ( relative risk ( RR ) = 0·52 , 95 % CI 0·30 , 0·92 ) or third tertile ( RR = 0·51 , 95 % CI 0·25 , 1·05 ) of the ' health conscious ' dietary pattern were about 50 % less likely to have high levels of PPD symptoms ( EPDS ≥ 13 ) compared with those in the lowest tertile . CONCLUSIONS This is the first prospect i ve study showing that a healthy diet during pregnancy is associated with reduced risk for PPD . Additional longitudinal studies and trials are needed to confirm these findings BACKGROUND The impact of prenatal depression on pregnancy outcomes is largely unknown . METHODS We conducted a population -based prospect i ve cohort study among pregnant women of the Kaiser Permanente Medical Care Program to examine the impact of prenatal depression on the risk of preterm delivery . We interviewed pregnant women in their early pregnancy . Women 's depressive symptoms were ascertained using the st and ard Center for Epidemiological Studies Depression Scale ( CESD ) . The presence of significant prenatal depressive symptoms and severe depressive symptoms was determined by CESD scores > or = 16 and > or = 22 , respectively . RESULTS Among the 791 participants who answered CESD questions and delivered a live birth , after controlling for potential confounders using the Cox proportional hazard regression , women with CESD scores > or = 16 had almost twice the risk of preterm delivery compared with women without depressive symptoms : adjusted hazard ratio ( aHR ) = 1.9 , 95 % confidence interval ( CI ) 1.0 - 3.7 . The risk of preterm delivery increased with increasing severity of depression : aHR = 1.6 ( CI 0.7 - 3.6 ) for CESD 16 - 21 and aHR = 2.2 ( CI 1.1 - 4.7 ) for CESD > or = 22 . The risk of preterm delivery associated with prenatal depression appears to be exacerbated by low educational level , a history of fertility problems and the presence of obesity and stressful events . The observed associations were not confounded by the use of antidepressants , although some of the associations did not reach statistical significance . CONCLUSIONS Our findings show that pregnant women with depressive symptoms are at increased risk of preterm delivery and , in addition , provide preliminary evidence that social and reproductive risk factors as well as obesity and stressful events may exacerbate the effect OBJECTIVE We assessed the relation between prepregnancy body mass index ( BMI ) and the likelihood of major depressive disorder ( MDD ) during pregnancy and tested whether this association was modified by gestational weight gain . METHOD Women ( N = 242 ) were enrolled at < 20 weeks gestation into a prospect i ve cohort study . Diagnosis of MDD was made with the Structured Clinical Interview for DSM-IV at 20 , 30 , and 36 weeks gestation . Gestational weight gain was compared with the 1990 Institute of Medicine weight gain recommendations . To assess the independent association between prepregnancy BMI and the odds of MDD , MDD at each time point was used as the dependent measure in a multivariable longitudinal logistic regression model employing generalized estimating equations . The data were collected from 2003 - 2007 . RESULTS There was a strong , positive dose-response association between prepregnancy BMI and the likelihood of MDD ( P = .002 ) . Compared with a BMI of 18 , the adjusted odds ratios ( 95 % confidence interval ) for BMI s of 23 , 28 , and 33 were 1.4 ( 1.1 to 1.7 ) , 1.9 ( 1.3 to 2.9 ) , and 2.6 ( 1.4 to 4.3 ) , respectively . Gestational weight gain significantly modified this effect . Among women with weight gains within and above the 1990 Institute of Medicine recommendations , pregravid overweight was associated with a greater likelihood of MDD . In contrast , all women with weight gains below recommended levels had an elevated odds of depression regardless of their pregravid BMI ( P < .05 ) . CONCLUSIONS Because pregravid overweight , poor gestational weight gain , and MDD all pose substantial risks for fetal development and birth outcomes , health care providers should monitor depression levels in these women to facilitate appropriate depression intervention 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 An ecological analysis found that the docosahexaenoic acid content in mother 's milk and seafood intake were inversely correlated with postpartum depression . This prospect i ve study investigated the relationship of consumption of selected high-fat foods and specific types of fatty acids with the risk of postpartum depression . METHOD The subjects were 865 Japanese women . Dietary data were obtained from a self-administered diet history question naire during pregnancy . The Edinburgh Postnatal Depression Scale ( EPDS ) was used for the evaluation of postpartum depression . Adjustment was made for age , gestation , parity , cigarette smoking , family structure , family income , education , changes in diet in the previous month , Output:	: Health care providers should be aware that women who are obese when they become pregnant are more likely to experience elevated antenatal and postpartum depression symptoms than normal-weight women , with intermediate risks for overweight women
MS2915	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background and Purpose — Treatment of intracerebral hematoma ( ICH ) is controversial . An advantage of neurosurgical intervention over conservative treatment of ICH has not been established . Recent reports suggest a favorable effect of stereotactic blood clot removal after liquefaction by means of a plasminogen activator . The SICHPA trial was aim ed at investigating the efficacy of this treatment . Methods — A stereotactically placed catheter was used to instill urokinase to liquefy and drain the ICH in 6-hour intervals over 48 hours . From 1996 to 1999 , 13 centers entered 71 patients into the study . Patients were r and omized into a surgical group ( n=36 ) and a nonsurgical group ( n=35 ) . Admission criteria were the following : age > 45 years , spontaneous supratentorial ICH , Glasgow Eye Motor score ranging from 2 to 10 , ICH volume > 10 cm3 , and treatment within 72 hours . The primary end point was death at 6 months . As secondary end points , ICH volume reduction and overall outcome measured by the modified Rankin scale were chosen . The trial was prematurely stopped as a result of slow patient accrual . Results — Seventy patients were analyzed . Overall mortality at day 180 after stroke was 57 % ; this included 20 of 36 patients ( 56 % ) in the surgical group and 20 of 34 patients ( 59 % ) in the nonsurgical group . A significant ICH volume reduction was achieved by the intervention ( 10 % to 20 % , P < 0.05 ) . Logistic regression analysis indicated the possibility of efficacy for surgical treatment ( odds ratio , 0.23 ; 95 % confidence interval , 0.05 to 1.20;P = 0.08 ) . The odds ratio of mortality combined with modified Rankin scale score 5 at 180 days was also not statistically significant ( odds ratio , 0.52 ; 95 % confidence interval , 1.2 to 2.3;P = 0.38 ) . Conclusions — Stereotactic aspiration can be performed safely and in a relatively uniform manner ; it leads to a modest reduction of 18 mL of hematoma reduction over 7 days when compared with control , which has a 7-mL reduction , and therefore may improve prognosis The purpose of this study was to judge the clinical value of minimally invasive stereotactic puncture and thrombolysis therapy ( MISPTT ) for acute intracerebral hemorrhage ( ICH ) . A r and omized control clinical trial was undertaken . According to the enrollment criteria , 122 acute ICH cases were analyzed , of which 64 cases received MISPTT ( MISPTT group , MG ) and 58 cases received conventional craniotomy ( CC group , CG ) . The Glasgow coma scale ( GCS ) scores , postoperative complications ( PC ) , and rebleeding incidences were compared . Moreover , 1 year postoperation , the long-term outcomes of patients with regard to hematoma volume ( HV ) < 50 mL and HV ≥50 mL were judged , respectively , by the Glasgow outcome scale ( GOS ) , Barthel index ( BI ) , modified Rankin Scale ( mRS ) , and case fatality ( CF ) . MG patients showed obvious amelioration in GCS score compared with that of CG patients . The total incidence of PC in MG decreased compared with that of CG . The incidences of rebleeding in MG and CG were 9.4 and 17.2 % , respectively ( P = 0.243 ) . There were no obvious differences between the CFs of MG and CG ( 17.2 and 25.9 % , respectively , P = 0.199 ) . The GOS , BI , and mRS representing long-term outcome for both HV < 50 mL and HV ≥50 mL in MG were ameliorated significantly greater than that in CG patients ( all P < 0.05 ) . These data suggest that there are advantages with MISPTT not only in trauma and safety , but the MISPTT group had fewer complications and a trend toward improved short-term and long-term outcomes Background Within the spectrum of spontaneous intracerebral haemorrhage there are some patients with large or space occupying haemorrhage who require surgery for neurological deterioration and others with small haematomas who should be managed conservatively . There is equipoise about the management of patients between these two extremes . In particular there is some evidence that patients with lobar haematomas and no intraventricular haemorrhage might benefit from haematoma evacuation . The STICH II study will establish whether a policy of earlier surgical evacuation of the haematoma in selected patients will improve outcome compared to a policy of initial conservative treatment . Methods / Design an international multicentre r and omised parallel group trial . Only patients for whom the treating neurosurgeon is in equipoise about the benefits of early craniotomy compared to initial conservative treatment are eligible . All patients must have a CT scan confirming spontaneous lobar intracerebral haemorrhage ( ≤1 cm from the cortex surface of the brain and 10 - 100 ml in volume ) . Any clotting or coagulation problems must be corrected and r and omisation must take place within 48 hours of ictus . With 600 patients , the study will be able to demonstrate a 12 % benefit from surgery ( 2p < 0.05 ) with 80 % power . Stratified r and omisation is undertaken using a central 24 hour r and omisation service accessed by telephone or web . Patients r and omised to early surgery should have the operation within 12 hours . Information about the status ( Glasgow Coma Score and focal signs ) of all patients through the first five days of their trial progress is also collected in addition to another CT scan at about five days ( + /- 2 days ) . Outcome is measured at six months via a postal question naire to the patient . Primary outcome is death or severe disability defined using a prognosis based 8 point Glasgow Outcome Scale . Secondary outcomes include : Mortality , Rankin , Barthel , EuroQol , and Survival . Trial Registration IS RCT N : IS RCT BACKGROUND Spontaneous supratentorial intracerebral haemorrhage accounts for 20 % of all stroke-related sudden neurological deficits , has the highest morbidity and mortality of all stroke , and the role of surgery remains controversial . We undertook a prospect i ve r and omised trial to compare early surgery with initial conservative treatment for patients with intracerebral haemorrhage . METHODS A parallel-group trial design was used . Early surgery combined haematoma evacuation ( within 24 h of r and omisation ) with medical treatment . Initial conservative treatment used medical treatment , although later evacuation was allowed if necessary . We used the eight-point Glasgow outcome scale obtained by postal question naires sent directly to patients at 6 months follow-up as the primary outcome measure . We divided the patients into good and poor prognosis groups on the basis of their clinical status at r and omisation . For the good prognosis group , a favourable outcome was defined as good recovery or moderate disability on the Glasgow outcome scale . For the poor prognosis group , a favourable outcome also included the upper level of severe disability . Analysis was by intention to treat . FINDINGS 1033 patients from 83 centres in 27 countries were r and omised to early surgery ( 503 ) or initial conservative treatment ( 530 ) . At 6 months , 51 patients were lost to follow-up , and 17 were alive with unknown status . Of 468 patients r and omised to early surgery , 122 ( 26 % ) had a favourable outcome compared with 118 ( 24 % ) of 496 r and omised to initial conservative treatment ( odds ratio 0.89 [ 95 % CI 0.66 - 1.19 ] , p=0.414 ) ; absolute benefit 2.3 % ( -3.2 to 7.7 ) , relative benefit 10 % ( -13 to 33 ) . INTERPRETATION Patients with spontaneous supratentorial intracerebral haemorrhage in neurosurgical units show no overall benefit from early surgery when compared with initial conservative treatment Objective : To perform a single-center pilot investigation of early hematoma removal in patients with intracerebral hemorrhage ( ICH ) . Background : Considerable debate remains regarding the utility of surgical clot evacuation for ICH . Methods : This was a prospect i ve trial of open craniotomy within 12 hours of ICH symptom onset versus best medical therapy . Patients were eligible if they had a nontraumatic ICH > 9 mL with significant neurologic impairment and were prepared for surgery within 12 hours of symptom onset . The study included a prospect i ve registry of patients and a r and omized trial . Results : The registry group included 34 medical and seven surgical patients . The surgical group had larger hemorrhages ( median , 96 mL ) and a lower Glasgow Coma Scale ( GCS ) score ( median , 10 ) compared with the medical group ( 33 mL ; GCS score , 13 ) . Six-month mortality was less in the medical group ( 36 % ) compared with the surgical group ( 54 % ) . In the r and omized series , median ICH volumes were similar in the surgical group ( n = 17 ; 49 mL ) compared with the medical group ( n = 17 ; 44 mL ) . Median GCS score was also similar ( medical , 10 ; surgical , 11 ) . Mortality was lower in the surgical group ( 6 % ) compared with the medical group ( 24 % ) at 1 month , but similar at 6 months ( surgical group , 17 % ; medical group , 24 % ) . Conclusion : A trial of early surgery for ICH is feasible . This study represents the largest prospect i ve , r and omized series of surgery for ICH . A modest early mortality benefit for surgery is possible , but long-term benefit for surgery was not established in this single-center pilot investigation St and ards of scientific reporting have evolved from the very beginning of scientific reporting . Virtually all journals now publish instructions for authors and most medical journals adhere to certain st and ards of publication . Such st and ards have been promoted by international groups such as the International Committee of Medical Journal Editors ( ICMJE ) and Committee on Publication Ethics ( COPE ) . The ICMJE has published general st and ards for crafting scientific articles : the “ Uniform Requirements for Manuscripts Su bmi tted to Biomedical Journals : Writing and Editing for Biomedical Publication ” [ 7 ] . These guidelines include suggestions not only for manuscript preparation , but also guidelines for ethical issues related to publishing . COPE , however , focuses on ethical issues [ 1 ] . CORR adheres to these guidelines ; authors may find links to these guidelines in our online Instructions for Authors . Such guidelines , as important as they are , lack sufficient detail to ensure all important information is included . Therefore , in addition to these general guidelines for preparing a manuscript , numerous international groups have published guidelines to ensure various sorts of studies contain all essential information . These include the CONSORT ( Consoli date d St and ards of Reporting Trials ) guidelines for r and omized trials [ 2 , 3 , 8 ] , QUORUM ( Quality of Reporting of Meta-analyses ) [ 6 ] and MOOSE ( Meta- analysis Of Observational Studies in Epidemiology ) [ 13 ] for meta-analyses , and STROBE ( Strengthening the Reporting of Observational Studies in Epidemiology ) for various sorts of observational studies ( the majority of clinical studies in surgical disciplines ) [ 12 , 15 ] . In essence , these guidelines tell investigators and authors what information is required to ensure readers ( and review ers ) can properly evaluate the study . Despite these st and ards , most reports of clinical studies lack such critical information . I suspect this is less by intent than lack of awareness of what information is required . In addition , although many journals , including CORR require a Level of Evidence [ 5 , 10 , 16 ] for studies involving patients , most clinical articles published in surgical journals have a relatively low level ; prospect i ve , r and omized trials are uncommon ( and often impractical ) , and even sufficiently large retrospective cohort studies to control for confounding variables may be unachievable for many conditions or treatments in single institutions . In the absence of high levels of evidence , systematic review s [ 9 , 11 , 17 ] and meta-analyses [ 4 ] have become increasingly common . My search of PubMed for articles limited to meta- analysis yielded 276 articles from 1950–1989 , 2116 from 1990–1994 , 3736 from 1995–1999 , 7920 from 2000–2004 , and 9313 from 2005 to 2009 . Most of these analyses undoubtedly collected information from lower level studies , thereby incurring the limitations of the individual studies . Virtually all systematic and meta-analyses we have recently published noted missing and variably reported data . In contrast to medical disciplines , surgical disciplines do not have the advantage of being able to conduct tightly design ed prospect i ve , r and omized , blinded , controlled trials . ( A PubMed search limited to r and omized controlled trials suggested The Journal of Bone and Joint Surgery and CORR had together published 556 RCTs and although I did not individually check these for quality , they reflect a small fraction of the articles both journals publish . ) For the foreseeable future , most of our information will arise from observational studies rather than prospect i ve trials . In this setting , it is especially important that each article contain all relevant information for future systematic review s and meta-analyses . The STROBE guidelines [ Output:	There is evidence that surgery is of benefit if undertaken early before the patient deteriorates .
MS2916	*TASK* the task is to summarize an input biomedical literature in six sentences *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 oral administration of a lozenge containing 11 mg (-)-menthol on nasal resistance to airflow ( NAR ) and nasal sensation of airflow in 62 subjects suffering from nasal congestion associated with naturally acquired common cold infection have been studied . NAR was measured by posterior rhinomanometry and nasal sensation of airflow by means of a visual analogue scale ( VAS ) . The effects of the lozenge were compared with a c and y placebo lozenge in a double blind r and omized trial . NAR showed a significant increase ( P less than 0.05 ) in both the menthol and placebo groups over the 2 h experiment with no difference between the groups at any time . The VAS scores showed significant changes of subjective improvement in nasal sensation of airflow ( P less than 0.001 ) in the menthol-treated group 10 min after dosing whereas the placebo group showed no change . It is concluded that dosing with 11 mg menthol in subjects with common cold has no effect on NAR as measured by posterior rhinomanometry but causes a marked change in nasal sensation of airflow with a subjective sensation of nasal decongestion Background Pseudoephedrine ( 60 mg ) is widely used as an oral decongestant taken in tablet or syrup formulations every 4–6 hours for the treatment of nasal congestion associated with common cold and allergy . However , there are relatively few studies in the literature that have used objective measures of nasal airway resistance ( NAR ) to assess the efficacy of pseudoephedrine , and most studies use only a single dose of medication . The present study has the aims of study ing the safety and efficacy of a new pseudoephedrine formulation after single and multiple doses in patients with URTI . Methods The study was a double-blind , r and omized , parallel-group , placebo-controlled trial conducted over three study days at a single center . Patients suffering from nasal congestion associated with common cold were recruited and total NAR was measured by the technique of posterior rhinomanometry . NAR and subjective scores of nasal congestion were measured at baseline and after dosing with study medication , every hour over a four-hour period on day 1 after a single dose , and on day 3 after multiple doses of medication . Subjective scores of congestion/stuffiness were also made as a summary score at the end of each day of treatment . Results Two hundred and thirty-eight patients with nasal congestion associated with acute upper respiratory tract infection ( URTI ) , mean age 20 years , were recruited to the study and received treatment . After a single dose on day 1 the pseudoephedrine group had a statistically significant lower area under the NAR curve than placebo ( p = 0.006 ) for the primary efficacy variable area under the NAR curve from 0–3 hours ( NAR AUC 0–3h ) , and similarly for the secondary efficacy variable NAR AUC 0–4h ( p = 0.001 ) . On day three after multiple doses , the pseudoephedrine group had a statistically significant lower NAR AUC 0–3h and AUC 0–4h than placebo ( p < 0.001 ) , On day 1 , the pseudoephedrine group had significantly lower subjective scores for congestion than placebo visual analog scale ( VAS ) AUC 0–3h ( p = 0.029 ) and similarly for VAS AUC 0–4h ( p = 0.021 ) . On day 3 , the differences in subjective scores were not significantly different . The mean decrease from baseline of the summary score for congestion/stuffiness over the duration of the study was greater in the pseudoephedrine group compared to the placebo group ( p = 0.016 ) . On average , heart rate was between two and four beats per minute greater in the pseudoephedrine group compared to placebo . Five adverse events were reported in both treatment groups and these were deemed to be unrelated to treatment . Conclusion The results demonstrate that pseudoephedrine is a safe and effective treatment for nasal congestion associated with URTI . The results from the laboratory study on day 1 demonstrate by both objective and subjective measures of nasal congestion that a single dose of 60 mg pseudoephedrine is superior to placebo treatment . Support for the decongestant efficacy of multiple doses of pseudoephedrine is provided by objective measures on day 3 and subjective measures made over three days , but not by the VAS scores on day 3 OBJECTIVE Nasal inhalation of steam has been proposed as treatment of viral colds on the assumption that increased intranasal temperature will inhibit replication of rhinovirus ( RV ) . The effect of steam inhalation on RV shedding by infected volunteers was examined in this study . DESIGN R and omized controlled trial . Volunteers experimentally infected with RV were treated with machine-generated humidified air , which was either hot ( active ) or at room temperature ( placebo ) . Viral shedding was assessed over the 4 days following treatment . SETTING Local hotel . PARTICIPANTS Twenty volunteers from the university community who were susceptible to the challenge virus . INTERVENTION Two 30-minute intranasal treatments , the first at 24 hours after inoculation and the second at 48 hours . The temperature of active vapor was 42 degrees C to 44 degrees C and of placebo vapor was 22 degrees C. MAIN OUTCOME MEASURES Viral titers in nasal washings on each of 5 days following inoculation . RESULTS Mean viral titers prior to the first treatment were 10(1.7 ) tissue culture infectious doses per milliliter in the active group and 10(1.5 ) in the placebo group . Mean titers for the next 4 days were 10(1.7 ) , and 10(1.7 ) , 10(1.2 ) , and 10(0.9)/mL in the active group and 10(1.8 ) , 10(1.9 ) , 10(1.6 ) , and 10(0.7)/mL in the placebo group ( no significant difference ) . The proportion of volunteers who shed virus on each day was also similar in the two groups . CONCLUSION Two nasal inhalation treatments with steam had no effect on viral shedding in volunteers with experimental RV colds A total of 466 healthy adults from four different regions of Engl and entered a double-blind , r and omised trial to test the effectiveness of an antihistamine ( triprolidine ) and a decongestant ( pseudoephedrine ) , alone or in combination , in relieving symptoms of the common cold . During the study 199 subjects reported a total of 243 colds . Subjects recorded the severity of 12 symptoms during treatment and noted separately the severity of a further seven symptoms that represented unwanted effects of treatment or served as an index of suggestibility . They were then asked about their overall improvement in symptoms during treatment and whether they thought they had taken placebo . Sneezing , nasal obstruction , and overall response to treatment were significantly improved ( p < 0.01 ) with psuedoephedrine or pseudoephedrine and triprolidine compared with placebo The effectiveness of orally administered pseudoephedrine in patients with acute or chronic nonsuppurative rhinitis was evaluated under double-blind conditions . Intranasally administered ephedrine which was given to all patients at the end of this study served as the positive control . Marked nasal decongestant effects of a single oral dose of pseudoephedrine ( 60 mg tablet ) , as determined by a modified passive anterior , rhinometrie technique occurred within 30 minutes and were maintained for at least four hours . The mean nasal decongestant response ( Δ% of baseline ) of 57.2 % was associated with a mean peak , plasma pseudoephedrine level of 274 ng/ml . In addition , the maximum response to oral pseudoephedrine treatment was equivalent to the response produced by ephedrine nasal spray . These results suggest that pseudoephedrine is an orally effective nasal decongestant We tested the hypothesis that antihistamine-decongestant combinations cause no clinical ly significant relief of the symptoms of upper respiratory tract infections in young children by r and omly assigning 96 children to one of three treatment groups : antihistamine-decongestant , placebo , and no treatment . There were no differences among the three study groups in the proportion of children considered " better " overall by the parent 48 hours after the initial assessment ( drug , 67 % ; placebo , 71 % ; no treatment , 57 % ; p = 0.53 ) . There were no differences among groups in individual or composite symptom score changes . Two thirds of parents whose children were eligible for the drug trial believed that their child needed medicine for cold symptoms . In the proportion of parents believing that their child needed medicine , there was no difference between those who consented to participate and those who refused . Parents who wanted medicine at the initial visit reported more improvement at follow-up , regardless of whether the child received drug , placebo , or no treatment . We conclude that there is no clinical ly significant improvement in symptoms of upper respiratory tract infection , including no significant placebo effect , in young children for whom an antihistamine-decongestant is prescribed A placebo-controlled double-blind r and omized trial was carried out to assess the efficacy of pseudoephedrine in relieving nasal congestion in the common cold . Fifty-four previously healthy persons who had a common cold for at least 5 days or less at the start of the study with moderate to severe nasal congestion were recruited , 52 completed the trial . Following a single dose of oral pseudoephedrine ( 60 mg capsule ) or placebo , symptoms of congestion improved significantly compared with placebo at times 60 , 90 , 120 , and 150 min after the dose . Total nasal minimum cross-sectional area and nasal volume measured by acoustic rhinometry increased significantly compared to placebo ( P = 0.018 and P = 0.003 , respectively ) after the dose . There was no significant change in nasal area as measured by active posterior rhinomanometry after pseudoephedrine compared to placebo . We conclude that in the acute common cold , a single 60 mg dose of pseudoephedrine produces significant increases in the dimensions of the nasal cavity compared to placebo and this is associated with a reduction in the symptom of congestion The aim of the trial was to examine the effectiveness of an oral decongestant in common cold . Thirty subjects with naturally acquired colds got a 100 mg sustained release tablet containing norephedrine on one day and a placebo tablet on another day in double blind design . Changes in nasal patency were assessed by rhinomanometry , measurement of nasal expiratory peak flow , and a self- assessment test , and the number of sneezes and of nose blowings were recorded in a 10 hours period after medication . Rhinomanometry , but not peak flow measurements showed a significant difference ( p less than 0.02 ) two hours after medication , and the self- assessment of nasal blockage showed that the effect lasted for the entire 10 hours observation period ( p less than 0.01 ) . Nasal respiration was reestablished in half of the blocked noses . There was no effect on number of sneezes and nose blowings . In conclusion , oral norephedrine has a moderate decongestant effect , which may justify its use in adults with common colds . This symptom amelioration must be balanced against cost of therapy and risk of side effects . A prevention of otitis media and of sinusitis has not been documented in the literature A VARIETY of drugs and drug formulations have been developed for the symptomatic relief of engorged mucous membranes which accompany coryza and upper respiratory infections . Existing objective techniques for measuring duration of drug effect include the determination of urinary excretion patterns1or blood levels2following drug administration . However , these are measurements of drug levels only inferentially related to therapeutic responses . Direct determinations of nasal airflow have been used occasionally to compare the effectiveness of formulations , and some of these rhinometric techniques have been review ed by Aviado,3Stoksted,4 and McLaurin.5,6The technique that we have developed is essentially a modification of that reported by McLaurin , dependent only upon a pressure transducer and a direct writing recorder . St and ard airflow measurements depend upon variations of pressure drop relative to a st and ard external pressure , an oxygen tank , for example . For our method we have eliminated the external pressure st and The utility of an anterior rhinomanometric method for the assessment of decongestant drug activity is illustrated with representative clinical data . Controlled studies employing topical nasal spray , nasal inhaler , and oral syrup formulations were conducted under single- or double-blind conditions in patients with allergic or coryzal rhinitis . The method provided an objective means to distinguish active from placebo ( vehicle ) treatments and to discriminate differences in decongestant activity between two active formulations . Furthermore , objective ly determined increases in nasal patency paralleled the patients ' subjective perception of improved airflow . In conclusion , this rhinomanometric methodology provided objective confirmation of drug activity with orally-administered , inhaled , and topically-applied decongestant drug formulations The aim of this study was to investigate the efficacy of pseudoephedrine as a nasal decongestant . Patients with nasal congestion associated with common cold received two doses of medication separated by 4 hours , either 60 mg pseudoephedrine ( n = 20 ) , or placebo ( n = 20 ) . Unilateral nasal airflow was measured over a 7-hour period to record the spontaneous changes in nasal airflow associated with the nasal cycle . Minimum ( F MIN ) and maximum ( F MAX ) unilateral nasal airflows were defined as the minimum and maximum nasal airflow values for each nasal passage recorded during the 7-hour Output:	There was a small but statistically significant 6 % decrease in subjective symptoms after a single dose of decongestant compared with placebo . This was supported by a significant decrease in nasal airways resistance . With repeated doses , nasal decongestants produce a very small statistical benefit of 4 % over three to five days , again supported by a decrease in nasal airways resistance . A single oral dose of nasal decongestant in the common cold is modestly effective for the short term relief of congestion in adults , and these drugs also provide benefit in some individuals after regular use over three to five days .
MS2917	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Type 2 diabetes is a major health problem in many countries including India . Yoga may be an effective type 2 diabetes prevention strategy in India , particularly given its cultural familiarity . Methods This was a parallel , r and omized controlled pilot study to collect feasibility and preliminary efficacy data on yoga for diabetes risk factors among people at high risk of diabetes . Primary outcomes included : changes in BMI , waist circumference , fasting blood glucose , postpr and ial blood glucose , insulin , insulin resistance , blood pressure , and cholesterol . We also looked at measures of psychological well-being including changes in depression , anxiety , positive and negative affect and perceived stress . Forty-one participants with elevated fasting blood glucose in Bangalore , India were r and omized to either yoga ( n = 21 ) or a walking control ( n = 20 ) . Participants were asked to either attend yoga classes or complete monitored walking 3–6 days per week for eight weeks . R and omization and allocation was performed using computer-generated r and om numbers and group assignments delivered in sealed , opaque envelopes generated by off-site study staff . Data were analyzed based on intention to treat . Results This study was feasible in terms of recruitment , retention and adherence . In addition , yoga participants had significantly greater reductions in weight , waist circumference and BMI versus control ( weight −0.8 ± 2.1 vs. 1.4 ± 3.6 , p = 0.02 ; waist circumference −4.2 ± 4.8 vs. 0.7 ± 4.2 , p < 0.01 ; BMI −0.2 ± 0.8 vs. 0.6 ± 1.6 , p = 0.05 ) . There were no between group differences in fasting blood glucose , postpr and ial blood glucose , insulin resistance or any other factors related to diabetes risk or psychological well-being . There were significant reductions in systolic and diastolic blood pressure , total cholesterol , anxiety , depression , negative affect and perceived stress in both the yoga intervention and walking control over the course of the study . Conclusion Among Indians with elevated fasting blood glucose , we found that participation in an 8-week yoga intervention was feasible and result ed in greater weight loss and reduction in waist circumference when compared to a walking control . Yoga offers a promising lifestyle intervention for decreasing weight-related type 2 diabetes risk factors and potentially increasing psychological well-being . Trial registration Clinical Trials.gov Identified NCT00090506 Background Heart failure ( HF ) and chronic obstructive pulmonary disease ( COPD ) are highly prevalent and associated with a large symptom burden , that is compounded in a dual HF- COPD diagnosis . Yoga has potential benefit for symptom relief ; however functional impairment hinders access to usual yoga classes . We developed a Tele-Yoga intervention and evaluated it in a controlled pilot trial . This paper reports on the appropriateness and acceptability of the intervention and the evaluation design . Methods A controlled , non-r and omised trial was conducted of an 8-week Tele-Yoga intervention versus an educational control ( information leaflets mailed to participants with one phone call a week ) . Biweekly one-hour Tele-Yoga classes were implemented via multipoint videoconferencing that connected participants to live classes via an Internet connection to their televisions . Semi-structured qualitative interviews were conducted with participants post study exit to explore reasons for and experiences of participating , including views of study outcome measures and physiological tests . Transcribed interviews were analysed using thematic content analysis . Results Fifteen people participated in the pilot study ( 7 in the intervention group , 8 in the control ) . Of these , 12 participants were interviewed , 6 in each group , mean age 71.2 years ( SD 10.09 ) ; 3 were male . Themes are reported in the following categories : acceptability and appropriateness of the intervention , potential active ingredients of the intervention , acceptability and appropriateness of the control , participation in the research , and acceptability of the testing procedures . The intervention was acceptable and appropriate : the intervention group reported enjoying yoga and valuing the home-based aspect and participants described a high symptom burden and social isolation . However , technological problems result ed in poor video-streaming quality for some participants . Potential active ingredients included physical postures , breathing exercises and guidance in relaxation and meditation . The educational control intervention was acceptable and appropriate , with participants reporting little effect on their well-being and no impact on mechanisms hypothesised to explain yoga ’s effectiveness . The question naires and home physiological testing were acceptable to participants . Conclusions Tele-Yoga is an acceptable and appropriate intervention in people with HF and COPD and further research is warranted to refine the technology used in its delivery . Findings provide guidance for research ers working in tele- interventions , yoga , and similar population s . Trial registration Clinical Trials.gov Identifier : NCT02078739 ( 4 March 2014 ) 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 AIMS The purpose of this study was to evaluate whether yoga training in addition to st and ard medical therapy can improve cardiac function and reduce N terminal pro B-type natriuretic peptide ( NT pro BNP ) in heart failure ( HF ) . METHODS 130 patients were recruited and r and omized into two groups : Control Group ( CG ) ( n = 65 ) , Yoga Group ( YG ) . In YG , 44 patients and in CG , 48 patients completed the study . Cardiac function using left ventricular ejection fraction ( LVEF ) , myocardial performance index ( Tei index ) , and NT pro BNP , a biomarker of HF , was assessed at baseline and after 12 weeks . RESULT Improvement in LVEF , Tei index , and NT pro BNP were statistically significant in both the groups . Furthermore , when the changes in before and after 12 weeks were in percentage , LVEF increased 36.88 % in the YG and 16.9 % in the CG , Tei index was reduced 27.87 % in the YG and 2.79 % in the CG , NT pro BNP was reduced 63.75 % in the YG and 10.77 % in the CG . The between group comparisons from pre to post 12 weeks were significant for YG improvements ( LVEF , P < 0.01 , Tei index , P < 0.01 , NT pro BNP , P < 0.01 ) . CONCLUSION These results indicate that the addition of yoga therapy to st and ard medical therapy for HF patients has a markedly better effect on cardiac function and reduced myocardial stress measured using NT pro BNP in patients with stable HF BACKGROUND Despite recent advances in pharmacologic and device therapy , morbidity and mortality from heart failure ( HF ) remain high . Yoga combines physical and breathing exercises that may benefit patients with HF . We hypothesized that an 8-week regimen of yoga in addition to st and ard medical therapy would improve exercise capacity , inflammatory markers , and quality of life ( QoL ) in patients with HF . METHODS AND RESULTS New York Heart Association Class I-III HF patients were r and omized to yoga treatment ( YT ) or st and ard medical therapy ( MT ) . Measurements included a grade d exercise test ( GXT ) to V O(2Peak ) and the following serum biomarkers : interleukin-6 ( IL-6 ) , high-sensitivity C-reactive protein ( hsCRP ) , and extracellular superoxide dismutase ( EC-SOD ) . The Minnesota Living with Heart Failure Question naire ( MLHFQ ) was administered to assess changes in QoL. A total of 19 patients were enrolled after the initial screening . Of the 19 patients , 9 were r and omized to YT and 10 to MT . Patients had a mean EF of 25 % . GXT time and V O(2Peak ) were significantly improved in the YT versus MT groups ( + 18 % in the YT and -7.5 % in MT ; P = .03 vs. control and + 17 in YT and -7.1 in MT ; P = .02 , respectively ) . There were statistically significant reductions in serum levels of IL-6 and hsCRP and an increase in EC-SOD in the YT group ( all P < .005 vs. MT ) . MLHFQ scores improved by 25.7 % in the YT group and by 2.9 % in the MT group . CONCLUSIONS Yoga improved exercise tolerance and positively affected levels of inflammatory markers in patients with HF , and there was also a trend toward improvements in CONTEXT Guidelines recommend that exercise training be considered for medically stable out patients with heart failure . Previous studies have not had adequate statistical power to measure the effects of exercise training on clinical outcomes . OBJECTIVE To test the efficacy and safety of exercise training among patients with heart failure . DESIGN , SETTING , AND PATIENTS Multicenter , r and omized controlled trial of 2331 medically stable out patients with heart failure and reduced ejection fraction . Participants in Heart Failure : A Controlled Trial Investigating Outcomes of Exercise Training ( HF-ACTION ) were r and omized from April 2003 through February 2007 at 82 centers within the United States , Canada , and France ; median follow-up was 30 months . INTERVENTIONS Usual care plus aerobic exercise training , consisting of 36 supervised sessions followed by home-based training , or usual care alone . MAIN OUTCOME MEASURES Composite primary end point of all-cause mortality or hospitalization and prespecified secondary end points of all-cause mortality , cardiovascular mortality or cardiovascular hospitalization , and cardiovascular mortality or heart failure hospitalization . RESULTS The median age was 59 years , 28 % were women , and 37 % had New York Heart Association class III or IV symptoms . Heart failure etiology was ischemic in 51 % , and median left ventricular ejection fraction was 25 % . Exercise adherence decreased from a median of 95 minutes per week during months 4 through 6 of follow-up to 74 minutes per week during months 10 through 12 . A total of 759 patients ( 65 % ) in the exercise training group died or were hospitalized compared with 796 patients ( 68 % ) in the usual care group ( hazard ratio [ HR ] , 0.93 [ 95 % confidence interval { CI } , 0.84 - 1.02 ] ; P = .13 ) . There were nonsignificant reductions in the exercise training group for mortality ( 189 patients [ 16 % ] in the exercise training group vs 198 patients [ 17 % ] in the usual care group ; HR , 0.96 [ 95 % CI , 0.79 - 1.17 ] ; P = .70 ) , cardiovascular mortality or cardiovascular hospitalization ( 632 [ 55 % ] in the exercise training group vs 677 [ 58 % ] in the usual care group ; HR , 0.92 [ 95 % CI , 0.83 - 1.03 ] ; P = .14 ) , and cardiovascular mortality or heart failure hospitalization ( 344 [ 30 % ] in the exercise training group vs 393 [ 34 % ] in the usual care group ; HR , 0.87 [ 95 % CI , 0.75 Output:	Software apps as exergames developed for use at home and community activity centers may minimize health disparities and increase QoL for HF patients
MS2918	*TASK* the task is to summarize an input biomedical literature in six sentences *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 This experimental study aim ed to compare the load-to-failure rate and stiffness of single- versus double-row suture techniques for repairing rotator cuff lesions using two different suture material s. Additionally , the mode of failure of each repair was evaluated . Method In 32 sheep shoulders , a st and ardized tear of the infraspinatus tendon was created . Then , n = 8 specimen were r and omized to four repair methods : ( 1 ) Double-row Anchor Ethibond ® coupled with polyester sutures , USP No. 2 ; ( 2 ) Double-Row Anchor HiFi ® with polyblend polyethylene sutures , USP No. 2 ; ( 3 ) Single-Row Anchor Ethibond ® coupled with braided polyester sutures , USP No. 2 ; and ( 4 ) Single-Row Anchor HiFi ® with braided polyblend polyethylene sutures , USP No. 2 . Arthroscopic Mason – Allen stitches were placed ( single-row ) and combined with medial horizontal mattress stitches ( double-row ) . All specimens were loaded to failure at a constant displacement rate on a material testing machine . Results Group 4 showed lowest load-to-failure result with 155.7 ± 31.1 N compared to group 1 ( 293.4 ± 16.1 N ) and group 2 ( 397.7 ± 7.4 N ) ( P < 0.001 ) . Stiffness was highest in group 2 ( 162 ± 7.3 N/mm ) and lowest in group 4 ( 84.4 ± 19.9 mm ) ( P < 0.001 ) . In group 4 , the main cause of failure was due to the suture cutting through the tendon ( n = 6 ) , a failure case observed in only n = 1 specimen in group 2 ( P < 0.001 ) . Conclusions A double-row technique combined with arthroscopic Mason-Allen/horizontal mattress stitches provides high initial failure strength and may minimize the risk of the polyethylene sutures cutting through the tendon in rotator cuff repair when a single load force is used Background Recurrent defects after open and arthroscopic rotator cuff repair are common . Double-row repair techniques may improve initial fixation and quality of rotator cuff repair . Purpose To evaluate the load to failure , cyclic displacement , and anatomical footprint of 4 arthroscopic rotator cuff repair techniques . Hypothesis Double-row suture anchor repair would have superior structural properties and would create a larger footprint compared to single-row repair . Study Design Controlled laboratory study . Methods Twenty fresh-frozen cadaveric shoulders were r and omly assigned to 4 arthroscopic repair techniques . The repair was performed as either a single-row technique or 1 of 3 double-row techniques : diamond , mattress double anchor , or modified mattress double anchor . Angle of loading , anchor type , bone mineral density , anchor distribution , angle of anchor insertion , arthroscopic technique , and suture type and size were all controlled . Footprint length and width were quantified before and after repair . Displacement with cyclic loading and load to failure were determined . Results There were no differences in load to failure and displacement with cyclic loading between the single-row repair and each double-row repair . All repair groups demonstrated load to failure greater than 250 N. A significantly greater supraspinatus footprint width was seen with double-row techniques compared to single-row repair . Conclusions The single-row repair technique was similar to the double-row techniques in load to failure , cyclic displacement , and gap formation . The double-row anchor repairs consistently restored a larger footprint than did the single-row method . Clinical Relevance The arthroscopic techniques studied have strong structural properties that approached the reported performance of open repair techniques . Double-row techniques provide a larger footprint width ; although not addressed by this study , such a factor may improve the biological quality of repair The aim of the study was to evaluate the time zero contact pressure over a defined rotator cuff footprint using different repair and stitch techniques in an established sheep model . Forty fresh-frozen sheep shoulders were r and omly assigned to five repair groups : single-row repair using simple stitches ( SRA-s ) , single-row repair using horizontal mattress stitches ( SRA-m ) , and single-row repair using arthroscopic Mason-Allen stitches ( SRA-ama ) . Double-row repair was either performed with a combination of simple and horizontal mattress stitches ( DRA-sm ) or with arthroscopic Mason-Allen/horizontal mattress stitches ( DRA-amam ) . Investigations were performed using a pressure-sensitive film system . The average contact pressure and pressure pattern were measured for each group . Contact pressure was lowest in SRA-m followed by SRA-s . SRA-ama showed highest contact pressure of all single-row treatment groups ( P < 0.05 ) . DRA-amam presented the highest overall contact pressure ( P < 0.05 ) , whereas DRA-sm exerted contact pressure equal to that of SRA-ama . Both double-row techniques showed the most exp and ed pressure pattern . Average contact pressures for the more complex single- and double-row techniques utilizing arthroscopic Mason-Allen stitches were greater than were those of the repair techniques utilizing simple and horizontal mattress stitches . However , the contact pattern between the anchors could be increased by using the double-row technique , result ing in more footprint coverage compared to patterns utilizing the single-row techniques . These results support the use of the more complex arthroscopic Mason-Allen stitches and may improve the environment for healing of the repaired rotator cuff tendon The purpose of this study was to identify potential predictors of function and tendon healing after arthroscopic rotator cuff repair that will enable the orthopaedic surgeon to determine which patients can expect a successful outcome . Between 2003 and 2005 , the Arthroscopic Rotator Cuff Registry was established to collect demographic , intraoperative , functional outcome , and ultrasound data prospect ively on all patients who underwent primary arthroscopic rotator cuff repair . At total of 193 patients met the study criteria , and 127 ( 65.8 % ) completed the 2-year follow-up . The most significant independent factors affecting ultrasound outcome were age ( odds ratio [ OR ] , 1.08 ; 95 % confidence interval [ CI ] , 1.02 - 1.14 ; P = .006 ) and tear size ( OR , 2.29 ; 95 % CI , 1.55 - 3.38 ; P < .001 ) . After adjustment for age and tear size , the intraoperative factors found to be significantly associated with a tendon defect were concomitant biceps procedures ( OR , 11.39 ; 95 % CI , 2.90 - 44.69 ; P < .001 ) and acromioclavicular joint procedures ( OR , 3.85 ; 95 % CI , 1.46 - 10.12 ; P = .006 ) . In contrast to the ultrasound data , the functional outcome variables , such as satisfaction ( OR , 3.92 ; 95 % CI , 2.00 - 7.68 ; P < .001 ) and strength ( OR , 10.05 ; 95 % CI , 1.61 - 62.77 ; P = .01 ) , had a greater role in predicting an American Shoulder and Elbow Surgeons score greater than 90 . The progression from a single-tendon rotator cuff tear to a multiple-tendon tear with associated pathology increased the likelihood of tendon defect by at least 9 times , and therefore , earlier surgical intervention for isolated , single-tendon rotator cuff tears could optimize the likelihood of ultrasound healing and an excellent functional outcome PURPOSE The purpose of this study was to determine biomechanical differences in cyclic elongation and ultimate strength between double-row rotator cuff repair and single-row repair for partial rotator cuff repairs . METHODS We r and omly assigned 18 immature bovine specimens ( aged 12 to 16 weeks ) to 3 repair groups ( 6 per group ) . A 1 x 2-cm defect was created at the infraspinatus tendon insertion site . Two suture anchors were implanted 1 cm apart at the anatomic insertion area for the lateral row . Two suture anchors were implanted 1 cm medial to the lateral row and 1 cm apart from each other for the medial row . Repair groups were constructed as follows : single-row repair with double-loaded suture anchors ( group 1 ) , double-row repair with single-loaded medial row and double-loaded lateral row ( group 2 ) , and double-row repair with single-loaded medial row and single-loaded lateral row ( group 3 ) . Specimens were cyclically loaded from 10 N to 90 N for 500 cycles and then loaded at 0.5 mm/s to failure . Data for cyclic elongation , with loads at 3 mm , 5 mm , and 10 mm , were analyzed via a 1-way analysis of variance ( P < .05 ) . RESULTS There were no significant differences for peak elongation after cyclic loading between groups . There were no significant differences between repair groups for loads at 3 mm , 5 mm , and 10 mm of elongation . Constructs typically failed by knot slippage ( 83 % ) , with a single sample having tendon-suture failure ( 17 % ) . CONCLUSIONS Double-row repair did not show a biomechanical advantage compared with single-row repair . With this result in mind , the theoretic advantage of a potentially larger footprint must be balanced against the added surgical time , complexity , and cost of double-row repair . CLINICAL RELEVANCE Arthroscopic surgeons should choose the best form of fixation for a given patient , without undue emphasis on single-row repair versus double-row repair . The clinical and biologic impact of footprint restoration was not addressed in this study The aim of the study was to evaluate the time zero mechanical properties of single- versus double-row configuration for rotator cuff repair in an animal model with consideration of the stitch technique and suture material . Thirty-two fresh-frozen sheep shoulders were r and omly assigned to four repair groups : suture anchor single-row repair coupled with ( 1 ) braided , nonabsorbable polyester suture sized USP No. 2 ( SRAE ) or ( 2 ) braided polyblend polyethylene suture sized No. 2 ( SRAH ) . The double-row repair was coupled with ( 3 ) USP No. 2 ( DRAE ) or ( 4 ) braided polyblend polyethylene suture No. 2 ( DRAH ) . Arthroscopic Mason – Allen stitches were used ( single-row ) and combined with medial horizontal mattress stitches ( double-row ) . Shoulders were cyclically loaded from 10 to 180 N. Displacement to gap formation of 5- and 10-mm at the repair site , cycles to failure , and the mode of failure were determined . The ultimate tensile strength was verified in specimens that resisted to 3,000 cycles . DRAE and DRAH had a lower frequency of 5- ( P = 0.135 ) and 10-mm gap formation ( P = 0.135 ) . All DRAE and DRAH resisted 3,000 cycles while only three SRAE and one SRAH resisted 3,000 cycles ( P < 0.001 ) . The ultimate tensile strength in double-row specimens was significantly higher than in others ( P < 0.001 ) . There was no significant variation in using different suture material ( P > 0.05 ) . Double-row suture anchor repair with arthroscopic Mason – Allen/medial mattress stitches provides initial strength superior to single-row repair with arthroscopic Mason – Allen stitches under isometric cyclic loading as well as under ultimate loading conditions . Our results support the concept of double-row fixation with arthroscopic Mason – Allen/medial mattress stitches in rotator cuff tears with improvement of initial fixation strength and ultimate tensile load . Use of new polyblend polyethylene suture material seems not to increase the initial biomechanical aspects of the repair construct The reported functional results of rotator cuff repair performed arthroscopically have been good . Only little is known about the cuff integrity after arthroscopic repair and how it influences the outcome . The aim of the study is to set a baseline of what rate of healing response respectively re-tears to expect and how cuff integrity alters the outcome . Fifty-three consecutive patients with an isolated supraspinatus tendon tear were arthroscopically operated and their tendons repaired . All pre- and postoperative data were prospect ively collected . At a minimum follow-up after 24 months ( average 26.4 months ) , the integrity of the cuff was evaluated by an open magnetic resonance imaging and the patients ’ function and satisfaction were documented and grade d to the sex- and age-related Constant-score also using a dynamometer for strength testing . The re-tear rate was 24.5 % with 13 non-healed tendons . The Constant-score of all patients improved significantly . The scores of the patients with a re-tear were significantly lower than those of the patient with an intact cuff . That was due to a less good performance in strength testing . The other categories of the Constant-score did not show any differences . The age of the patients with a re-tear was significantly higher . With the exception of age , we did not find any negative prognostic factor for a re-tear , and with the exception of re-tear no other factor influenced the Constant-score . Arthroscopic supraspinatus tendon repair yields a re-tear rate of 25 % which is comparable with the results of open or mini/open repair . Cuff integrity influences postoperative strength and Constant-score . Patients older than 65 years show a higher re-tear rate . Therapeutic Level IV is the level of evidence Th Output:	Traditional open rotator cuff repairs using tranosseous bone tunnels had the advantage of reapproximating the rotator cuff tendon solidly onto the greater tuberosity
MS2919	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Opioid misuse can complicate chronic pain management , and the non-medical use of opioids is a growing public health problem . The incidence and risk factors for opioid misuse in patients with chronic pain , however , have not been well characterized . We conducted a prospect i ve cohort study to determine the one-year incidence and predictors of opioid misuse among patients enrolled in a chronic pain disease management program within an academic internal medicine practice . Methods One-hundred and ninety-six opioid-treated patients with chronic , non-cancer pain of at least three months duration were monitored for opioid misuse at pre-defined intervals . Opioid misuse was defined as : 1 . Negative urine toxicological screen ( UTS ) for prescribed opioids ; 2 . UTS positive for opioids or controlled substances not prescribed by our practice ; 3 . Evidence of procurement of opioids from multiple providers ; 4 . Diversion of opioids ; 5 . Prescription forgery ; or 6 . Stimulants ( cocaine or amphetamines ) on UTS . Results The mean patient age was 52 years , 55 % were male , and 75 % were white . Sixty-two of 196 ( 32 % ) patients committed opioid misuse . Detection of cocaine or amphetamines on UTS was the most common form of misuse ( 40.3 % of misusers ) . In bivariate analysis , misusers were more likely than non-misusers to be younger ( 48 years vs 54 years , p < 0.001 ) , male ( 59.6 % vs. 38 % ; p = 0.023 ) , have past alcohol abuse ( 44 % vs 23 % ; p = 0.004 ) , past cocaine abuse ( 68 % vs 21 % ; p < 0.001 ) , or have a previous drug or DUI conviction ( 40 % vs 11 % ; p < 0.001 % ) . In multivariate analyses , age , past cocaine abuse ( OR , 4.3 ) , drug or DUI conviction ( OR , 2.6 ) , and a past alcohol abuse ( OR , 2.6 ) persisted as predictors of misuse . Race , income , education , depression score , disability score , pain score , and literacy were not associated with misuse . No relationship between pain scores and misuse emerged . Conclusion Opioid misuse occurred frequently in chronic pain patients in a pain management program within an academic primary care practice . Patients with a history of alcohol or cocaine abuse and alcohol or drug related convictions should be carefully evaluated and followed for signs of misuse if opioids are prescribed . Structured monitoring for opioid misuse can potentially ensure the appropriate use of opioids in chronic pain management and mitigate adverse public health effects of diversion A r and om sample of 1,200 employees of a steel manufacturing plant were r and omly assigned to four different self-report methods of assessing illicit drug use : 1 ) Individual interview in the workplace , 2 ) group-administered question naire in the workplace , 3 ) telephone interview , and 4 ) individual interview off the worksite . Urine specimens were collected and analyzed on all 928 subjects participating in the study , and hair analysis was conducted on 307 of the subjects . Although self-reports produced the highest drug use prevalence rate , analyses combining the results of the three assessment methods showed that the actual prevalence rate was approximately 50 % higher than the estimate produced by self-reports . The group-administered question naire condition produced prevalence rates that were roughly half those of the other self-report methods . The findings cast doubt on the validity of self-reports as a means of estimating drug use prevalence and suggest the need for multiple assessment methods Objective To examine the incidence of abnormal urine toxicology screening among chronic pain patients prescribed opioids for their pain and to relate these results to patient descriptors and type , number , and dose of prescribed opioids . Methods A retrospective analysis of data from 470 patients who had urine screening at a pain management program in an urban teaching hospital was performed . Urine sample s were analyzed using gas chromatography-mass spectrometry . Patients were categorized as having urine screens that were “ normal ” ( expected findings based on their prescribed drugs ) or abnormal . Abnormal findings were those of ( 1 ) absence of a prescribed opioid , ( 2 ) presence of an additional nonprescribed controlled substance , ( 3 ) detection of an illicit substance , and ( 4 ) an adulterated urine sample . Results Forty-five percent of the patients were found to have abnormal urine screens . Twenty percent were categorized as having an illicit substance in their urine . Illicit substances and additional drugs were found more frequently in younger patients than in older patients ( P<0.001 ) . No other variables were found to predict abnormal urine screen results . Discussion These results confirm past findings that r and om urine toxicology screens among patients prescribed opioids for pain reveal a high incidence of abnormal findings . Common patient descriptors , and number , type , and dose of prescribed opioids were found to be poor predictors of abnormal results This study introduces the Addiction Behaviors Checklist ( ABC ) , which is a brief ( 20-item ) instrument design ed to track behaviors characteristic of addiction related to prescription opioid medications in chronic pain population s. Items are focused on observable behaviors noted both during and between clinic visits . One hundred thirty-six consecutive veterans in a multidisciplinary Veterans Affairs Chronic Pain Clinic who were receiving long-term opioid medication treatment were included in this study . This study represents one of the first to follow a sample of chronic pain patients on opioid therapy over time , using a structured assessment tool to evaluate and track behaviors suggestive of addiction . Interrater reliability and concurrent validity data are presented , as well as a cut-off score for use in determining inappropriate medication use . The psychometric findings support the ABC as a viable assessment tool that can increase a provider 's confidence in determinations of appropriate vs. inappropriate opioid use & NA ; Prescribing long‐term opioids for patients with chronic pain is controversial . The primary purpose of this study was to examine physicians ' beliefs about and prescribing of the long‐term use of opioids in the treatment of chronic pain patients . Concerns about regulatory pressure and appropriateness of education regarding opioids were also examined . The design was a stratified r and om sample . In the United States , 6962 physicians were r and omly selected from two states in each of five regions of the country ( Northeast , Midwest , Southeast , Southwest , and Pacific ) . Physicians from seven medical specialties ( Family Practice , Internal Medicine , Physical Medicine and Rehabilitation , Rheumatology , Orthopedic Surgery , Neurosurgery , and Neurology ) were surveyed and 1912 ( 27.46 % ) responded . A survey consisting of questions regarding years of practice , number of chronic pain patients treated , frequency of prescribing long‐term opioids , concerns about opioids , goals of treatment , beliefs about education regarding opioids , and concerns about regulatory pressures was used . Based on the physicians who responded , it appears that prescription of long‐term opioids is relatively wide‐spread . Differences were noted by region , specialty , and the requirement for the use of multiple prescriptions for schedule II drugs . Physicians in the Midwestern United States were the least likely to prescribe the long‐term use of opioids . Rheumatologists and general practitioners were significantly more likely to prescribe long‐term opioids than were surgeons , neurologists , or physiatrists and were more likely to emphasize the importance of symptom improvement as an appropriate goal even in the absence of functional improvements . The majority of the respondents expressed relatively little concern about tolerance , dependence , and addiction as impediments to prescribing opioids . Physicians from states requiring multiple prescriptions reported that this legal requirement had little impact on their practice Abstract OBJECTIVES : To define the spectrum of chronic noncancer pain treated with opioid medications in 2 primary care setting s , and the prevalence of psychiatric comorbidity in this patient population . We also sought to determine the proportion of patients who manifested prescription opioid abuse behaviors and the factors associated with these behaviors . DESIGN : A retrospective cohort study . SETTING : A VA primary care clinic and an urban hospital-based primary care center ( PCC ) located in the northeastern United States . PATIENTS : A r and om sample of VA patients ( n=50 ) and all PCC patients ( n=48 ) with chronic noncancer pain who received 6 or more months of opioid prescriptions during a 1-year period ( April 1 , 1997 through March 31 , 1998 ) and were not on methadone maintenance . MEASUREMENTS : Information regarding patients ’ type of chronic pain disorder , demographic , medical , and psychiatric status , and the presence of prescription opioid abuse behaviors was obtained by medical record review . MAIN RESULTS : Low back pain was the most common disorder accounting for 44 % and 25 % of all chronic pain diagnoses in the VA and PCC sample s , respectively , followed by injury-related ( 10 % and 13 % ) , diabetic neuropathy ( 8 % and 10 % ) , degenerative joint disease ( 16 % and 13 % ) , spinal stenosis ( 10 % and 4 % ) , headache ( 4 % and 13 % ) and other chronic pain disorders ( 8 % and 22 % ) . The median duration of pain was 10 years ( range 3 to 50 years ) in the VA and 13 years in the PCC sample ( range 1 to 49 years ) . Among VA and PCC patients , the lifetime prevalence rates of psychiatric comorbidities were : depressive disorder ( 44 % and 54 % ) , anxiety disorder ( 20 % and 21 % ) , alcohol abuse/dependence ( 46 % and 31 % ) , and narcotic abuse/dependence ( 18 % and 38 % ) . Prescription opioid abusive behaviors were recorded for 24 % of VA and 31 % of PCC patients . A lifetime history of a substance use disorder ( adjusted odds ratio [ OR ] , 3.8 ; 95 % confidence interval [ CI ] , 1.4 to 10.8 ) and age ( adjusted OR , 0.94 ; 95 % CI , 0.89 to 0.99 ) were independent predictors of prescription opioid abuse behavior . CONCLUSIONS : A broad spectrum of chronic noncancer pain disorders are treated with opioid medications in primary care setting s. The lifetime prevalence of psychiatric comorbidity was substantial in our study population . A significant minority of patients manifested prescription opioid abusive behaviors , and a lifetime history of a substance use disorder and decreasing age were associated with prescription opioid abuse behavior . Prospect i ve studies are needed to determine the potential benefits as well as risks associated with opioid use for chronic noncancer pain in primary care OBJECTIVE To provide clinicians with a brief screening tool to predict accurately which individuals may develop aberrant behaviors when prescribed opioids for chronic pain . DESIGN One hundred and eighty-five consecutive new patients treated in one pain clinic took the self-administered Opioid Risk Tool ( ORT ) . The ORT measured the following risk factors associated in scientific literature with substance abuse : personal and family history of substance abuse ; age ; history of preadolescent sexual abuse ; and certain psychological diseases . Patients received scores of 0 - 3 ( low risk ) , 4 - 7 ( moderate risk ) , or > or= 8 ( high risk ) , indicating the probability of their displaying opioid-related aberrant behaviors . All patients were monitored for aberrant behaviors for 12 months after their initial visits . RESULTS For those patients with a risk category of low , 17 out of 18 ( 94.4 % ) did not display an aberrant behavior . For those patients with a risk category of high , 40 out of 44 ( 90.9 % ) did display an aberrant behavior . The authors used the c statistic to vali date the ORT , because it simultaneously assesses sensitivity and specificity . The ORT displayed excellent discrimination for both the male ( c = 0.82 ) and the female ( c = 0.85 ) prognostic models . CONCLUSION In a preliminary study , among patients prescribed opioids for chronic pain , the ORT exhibited a high degree of sensitivity and specificity for determining which individuals are at risk for opioid-related , aberrant behaviors . Further studies in a variety of pain and nonpain setting s are needed to determine the ORT 's universal applicability Assessing for the presence of addiction in the chronic pain patient receiving chronic opioid analgesia is a challenging clinical task . This paper presents a recently developed screening tool for addictive disease in chronic pain patients , and pilot efficacy data describing its ability to do so . In a small sample of patients ( n = 52 ) referred from a multidisciplinary pain center for " problematic " medication use , responses to the screening question naire were compared between patients who met combined diagnostic criteria for a substance use disorder and those who did not , as assessed by a trained addiction medicine specialist . Responses of addicted patients significantly differed from those of nonaddicted patients on multiple screening items , with the two groups easily differentiated by total question naire score . Further , three key screening indicators were identified as excellent predictors for the presence of addictive disease in this sample of chronic pain patients OBJECTIVES Opiates are commonly used to treat patients with chronic nonmalignant pain . There is much controversy over the definition , incidence , and risk factors of prescription opiate abuse in chronic pain treatment . The present study , done at the Seattle VA Medical Center , was design ed to create opiate abuse criteria , Output:	Review of the published studies reveals that no one procedure or set of predictor variables is sufficient to identify CPP at-risk for opioid misuse or abuse . Strong predictors include a personal history of illicit drug and alcohol abuse .
MS2920	*TASK* the task is to summarize an input biomedical literature in six sentences *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 As the number of patients aged > /=65 years starting haemodialysis ( HD ) continues to increase , more patients are at risk of falls , functional decline and cognitive impairment . In an earlier prospect i ve cohort study , we showed that 44 % of elderly HD patients had more than one fall within a 1-year period . The objective of this study was to assess whether falls remained predictive of increased mortality risk even after controlling for age , comorbidity , dialysis vintage and laboratory variables . METHODS Using a prospect i ve , cohort study design , patients aged > /=65 years and on chronic HD during the period April 2002 - 2003 were recruited . Patients were followed biweekly , and falls occurring within the first year were recorded . Outcome data were collected until death , study end ( 30 December 2006 ) , transplantation or transfer to another dialysis centre . RESULTS A total of 162 patients were followed for a median of 32.7 months ( quartiles 14 - 57 ) . In a univariate Cox model with a time-dependent variable for falls status , survival was worse amongst fallers compared to non-fallers ( HR 2.13 , 95 % CI 1.32 - 3.45 ; P = 0.002 ) . After adjustment for age , dialysis vintage , comorbidity and laboratory variables , falls were a significant predictor of mortality ( HR 1.78 , 95 % CI 1.07 - 2.98 , P = 0.03 ) . Exclusion of falls associated with concurrent illnesses did not alter the results ( HR 1.63 , CI 1.02 - 2.28 P = 0.05 ) . CONCLUSIONS We conclude that the occurrence of more than one accidental fall in a community-dwelling HD patient aged > /=65 years is associated with an independent increased risk of death . As fall interventions are effective , screening HD patients for falls may be a simple measure of clinical importance The goal of the study was to compare effectiveness of regional and local anesthesia in dialysis arterio-venous fistula ( AVF ) operations . It was a prospect i ve , r and omized study . 103 patients with end stage renal disease underwent AVF operations on upper limb . The patients have been r and omly divided in two groups . Group I : 49 patients in whom the operations have been done under the local anesthesia ; and Group II : 54 patients in whom the operation has been performed under the vertical infraclavicular block . Duplex sonography evaluation of upper arm vessels was performed pre-operatively and at 1 , 3 and 6 months postoperatively . Following parameters were measured on duplex scan : vessel diameter , blood flow rates ( PSV and EDV ) , resistive index ( RI ) and pulsatility index ( PI ) . Significantly less number of patients with regional anesthesia required additional perioperative analgesics as compared with the local anesthesia group . Time to postoperative pain initiation , need for postoperative pain killers was significantly better in Group II as compared with the Group I. Duration of operation was significantly less in regional as compared with local anesthesia . Postoperative PSV and EDVs were negatively correlated with patient age . The fistula maturation time was positively correlated with age . The vein diameter , postoperative PSV and EDV have been significantly increased in Group I as compared with Group II . The postoperative PI has significantly increased and RI has significantly decreased in Group I as compared with Group II . The total number of dialysis punctures was higher in regional as compared with the local anesthesia . Regional anesthesia provides significantly better analgesia as compared with the local anesthesia in AVF operations . It significantly improves the duplex sonography parameters after AVF formation . It can be a method of choice for some forms of fistulas Purpose Assessment of the effectiveness of Brachial Plexus Block ( BPB ) via axillary approach compared to regional anesthesia for arteriovenous fistula surgery in patients affected by end-stage renal disease . Methods We compared forty patients r and omly divided into two groups . Group A underwent BPB procedure with 15 mL ropivacaine 1 % and 10 mL of saline ( 0.9 % NaCl ) via axillary approach . Group B received local anesthesia with lidocaine 2 % . The forearm blood vessels were assessed by Doppler ultrasonography before and after the intervention . Results BPB performed on Group A was associated with a considerable venous dilation and a significant decrease ( 48.7 % , P<.05 ) in pulsatility index ( PI ) measured by Doppler ultrasound . In Group B , PI and venous dilation remained unaltered in the postoperative phase . No complications such as thrombosis or occlusion were encountered among patients who underwent BPB . Conclusions The axillary-approached BPB was more advantageous than local anesthesia . Its effectiveness was because of venous dilation and the decrease in the PI , consequent to the reduction in peripheral resistances and the increase in local blood flow , thus offering an ideal background for fistula creation and short-term patency BACKGROUND Central venous catheters ( CVC ) are a potential source of bacteraemia and have been associated with increased mortality in haemodialysis patients . We aim ed to investigate the relationships between haemodialysis vascular access , taking into account changes in vascular access type during patients ' lives , and cause specific mortality risk in a national cohort of dialysis patients . METHODS Prospect i ve cohort study including all patients receiving haemodialysis in Scotl and at annual cross sectional surveys in 2009 , 2010 and 2011 . Data were collected through the Scottish Renal Registry and by a structured review of case records following death . Cox proportional hazards regression and multivariable logistic regression were used to model survival and risk of death from septicaemia respectively . RESULTS Of a cohort of 2666 patients , 873 ( 32 % ) died during follow-up . After case-mix adjustment , patients using only tunnelled CVC during follow-up had a higher risk of all cause mortality across all strata of prior renal replacement therapy exposure [ adjusted hazard ratio ( HR ) : 1.83 - 2.08 ] . Case-mix adjusted risks of cardiovascular death ( adjusted HR : 2.20 - 2.95 ) and infection-related death ( adjusted HR : 3.10 - 3.63 ) were also higher in this group . Patients using tunnelled CVCs during follow-up and prior to death had 6.9-fold higher odds of death from septicaemia compared with those using only arteriovenous fistulae or grafts . CONCLUSION Compared with an arteriovenous fistula or graft , sustained use of tunnelled CVCs for vascular access is associated with higher risks of all-cause , cardiovascular and infection-related mortality Background An arteriovenous fistula is the optimal form of vascular access in patients with end-stage renal failure requiring haemodialysis . Unfortunately , approximately one-third of fistulae fail at an early stage . Different anaesthetic techniques can influence factors associated with fistula success , such as intraoperative blood flow and venous diameter . A regional anaesthetic brachial plexus block results in vasodilatation and improved short- and long-term fistula flow compared to the infiltration of local anaesthetic alone . This , however , has not yet been shown in a large trial to influence long-term fistula patency , the ultimate clinical measure of success . The aim of this study is to compare whether a regional anaesthetic block , compared to local anaesthetic infiltration , can improve long-term fistula patency . Methods This study is an observer-blinded , r and omised controlled trial . Patients scheduled to undergo creation of either brachial or radial arteriovenous fistulae will receive a study information sheet , and consent will be obtained in keeping with the Declaration of Helsinki . Patients will be r and omised to receive either : ( i ) an ultrasound guided brachial plexus block using lignocaine with adrenaline and levobupivicaine , or ( ii ) local anaesthetic infiltration with lignocaine and levobupivicaine . A total of 126 patients will be recruited . The primary outcome is fistula primary patency at three months . Secondary outcomes include primary patency at 1 and 12 months , secondary patency and fistula flow at 1 , 3 and 12 months , flow on first haemodialysis , procedural pain , patient satisfaction , change in cephalic vein diameter pre- and post-anaesthetic , change in radial or brachial artery flow pre- and post-anaesthetic , alteration of the surgical plan after anaesthesia as guided by vascular mapping with ultrasound , and fistula infection requiring antibiotics . Conclusions No large r and omised controlled trial has examined the influence of brachial plexus block compared with local anaesthetic infiltration on the long-term patency of arteriovenous fistulae . If the performance of brachial plexus block increases fistulae patency , this will have significant clinical and financial benefits as the number of patients able to commence haemodialysis when planned should increase , and the number of “ redo ” or revision procedures should be reduced . Trial registration This study has been approved by the West of Scotl and Research Ethics Committee 5 ( reference no. 12/WS/0199 ) and is registered with the Clinical Trials.gov data base ( reference no. NCT01706354 ) The use of ultrasound reduces the onset time , improves the quality of sensory block , and minimizes the risks associated with the supraclavicular approach for brachial plexus and stellate ganglion blockade . The present study was design ed to evaluate whether ultrasound also facilitates the approach for 3-in-1 blocks . Forty patients ( ASA physical status II or III ) undergoing hip surgery after trauma were r and omly assigned to two groups . In the ultrasound ( US ) group , 20 mL bupivacaine 0.5 % was administered under US guidance , whereas in the control group , the same amount and concentration of local anesthetic was administered with the assistance of a nerve stimulator ( NS ) . After US- or NS-based identification of the femoral nerve , the local anesthetic solution was administered , and the distribution of the local anesthetic solution was visualized and recorded on videotape in the US group . The quality and the onset of the sensory block was assessed by using the pinprick test in the central sensory region of each of the three nerves and compared with the same stimulation on the contralateral leg every 10 min for 60 min . The rating was performed using a scale from 100 % ( uncompromised sensibility ) to 0 % ( no sensory sensation ) . Heart rate , noninvasive blood pressure , and oxygen saturation were measured at short intervals for 60 min . The onset of sensory blockade was significantly shorter in Group US compared with Group NS ( US 16 + /- 14 min , NS 27 + /- 16 min , P < 0.05 ) . The quality of the sensory block after injection of the local anesthetic was also significantly better in Group US compared with Group NS ( US 15 % + /- 10 % of initial value , NS 27 % + /- 14 % of initial value , P < 0.05 ) . A good analgesic effect was achieved in 95 % of the patients in the US group and in 85 % of the patients in the NS group . In the US group , visualization of the cannula tip , the femoral nerve , the major vessels , and the local anesthetic spread was possible in 85 % of patients . Incidental arterial puncture ( n = 3 ) was observed only in the NS group . We conclude that an US-guided approach for 3-in-1 block reduces the onset time , improves the quality of the sensory block and minimizes the risks associated with this regional anesthetic technique . Implication s : The onset time and the quality of a regional anesthetic technique for the lower extremity is improved by ultrasonographic nerve identification compared with older techniques . ( Anesth Analg 1997;85:854 - 7 OBJECTIVE To reduce the onset of 0.5 % bupivacaine by adding 2 % lidocaine with 0.5 % bupivacaine for ultrasound-guided and double stimulation technique at musculocutaneous and radial nerve for infraclavicular brachial plexus block . DESIGN Prospect i ve r and omized double-blinded , controlled trial study . MATERIAL AND METHOD 90 patients undergoing creation of arteriovenous fistula under ultrasound-guided infraclavicular brachial plexus block were r and omized into 2 groups . Gr B ( 46 patients ) received 0.5 % bupivacaine 30 mL and Gr BL ( 44 patients ) received mixture of 0.5 % bupivacaine 20 mL and 2 % lidocaine 10 mL. The onset of sensory block were assessed by response to pinprick ( grading : 0 = no sensation , 1 = hypoesthesia , and 2 = normal sensation ) . Rescue analgesia during the operation , duration of sensory and motor blockade were recorded . Surgeon and patient satisfactions are also evaluated using 6-point scale ( 0 = dissatisfied to 5 = very satisfied ) . RESULTS There were no significant difference in the onset time of either group . Duration of sensory and motor block was not different . Surgeons ' and patients ' satisfaction were also not significantly different between the groups . CONCLUSION Mixing 2 % lidocaine with 0.5 % bupivacaine to the final concentration of 0.67%for lid Output:	In conclusion , RA was associated with higher primary patency rates of AVF and improved local blood flow in comparison to LA ; however , both procedures were comparable in terms of primary failure rates and postoperative complications .
MS2921	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: This study examined whether a culturally adapted version of a previously evaluated efficacious HIV prevention program reduced sexual risk behaviors of youth living with HIV ( YLH ) in Ug and a. YLH , 14 to 21 years , were r and omized to intervention ( N = 50 ) or control ( N = 50 ) conditions . Significantly more YLH in the intervention used condoms consistently and decreased their number of sexual partners in comparison to the control condition . Western interventions can be culturally adapted to retain efficacy in reducing the sexual risk behavior of YLH Background Long-acting reversible contraceptives ( LARCs ) and sterilisation are the most cost-effective methods of contraception but are rarely used in sub-Saharan Africa partly due to limited access . Study design HIV-positive pregnant women attending two urban clinics in Rw and a were followed prospect ively in a perinatal HIV transmission cohort study . Women attending one clinic were referred to public family planning ( FP ) services for all contraceptive methods ( Site A ) and women attending the other clinic ( Site B ) were offered implants and intrauterine devices ( IUDs ) on-site . Results Fifty three percent of the pregnant women reported an intention to use a LARC or to be sterilised after delivery . The uptake of implants was significantly higher at Site B ( 38 % ) than at Site A ( 6 % ) . The IUD uptake was extremely low at both sites ( 2 % ) . Twenty-eight of the 39 women at Site B who had intended to start using a LARC actually did so as compared to only one of 23 at Site A. Conclusion When access to LARC was provided , a substantial number of HIV-positive women started using hormonal implants , but not IUDs , in the postpartum period . HIV and FP services should consider improving access to implants to reduce the number of unintended pregnancies Objective : To evaluate a multipronged approach to promote dual contraceptive use by women within heterosexual HIV-1-serodiscordant partnerships . Methods : For 213 HIV-1-serodiscordant couples in Thika , Kenya , participating in an HIV-1 prevention clinical trial , contraceptive promotion was initiated through a multipronged intervention that included staff training , couples family planning sessions , and free provision of hormonal contraception on-site . Contraceptive use and pregnancy incidence were compared between two time periods ( before versus after June 2007 , when the intervention was initiated ) and between Thika and other Kenyan trial sites ( Eldoret , Kisumu , and Nairobi ) . Generalized estimating equations and And ersen – Gill proportional hazards modeling were used . Results : Nonbarrier contraceptive use increased after implementation of the intervention : from 31.5 to 64.7 % of visits among HIV-1-seropositive women [ odds ratio 4.0 , 95 % confidence interval ( CI ) 3.0–5.3 ] and from 28.6 to 46.7 % of visits among HIV-1-seronegative women ( odds ratio 2.2 , 95 % CI 1.4–3.5 ) . In comparison , at the other Kenyan sites , where the intervention was not implemented , contraceptive use changed minimally , from 15.6 to 22.3 % of visits for HIV-1-seropositive women and from 13.6 to 12.7 % among HIV-1-seronegative women . Self-reported condom use remained high during follow-up . Pregnancy incidence at the Thika was significantly lower after compared with before June 2007 ( hazard ratio 0.2 , 95 % CI 0.1–0.6 ) and was approximately half that at other Kenyan sites during the intervention period ( hazard ratio 0.5 , 95 % CI 0.3–0.8 ) . Conclusion : A multipronged family planning intervention can lead to high nonbarrier contraceptive uptake and reduced pregnancy incidence among women in HIV-1-serodiscordant partnerships BACKGROUND Dual protection is recommended for prevention of unwanted pregnancies and protection against sexually transmitted infections , including HIV . It is critical for HIV-negative women to prevent seroconversion and HIV transmission to their infants during pregnancy and breastfeeding . METHODS Women were followed up after delivery , monthly for the first 9 months and then 3-monthly to 24 months , in a cohort study investigating postnatal HIV transmission . Study nurses discussed family planning , including condom use , at each visit . Contraceptive methods used since the last visit were recorded . All women knew their HIV status , and most women breastfed for a minimum of 6 months . RESULTS Among 1,137 HIV-positive and 1 220 HIV-negative women the most common contraceptive method was the hormonal injectable ; few women used condoms alone or as dual contraception ( 0 - 3 months 6.8 % ; 7 - 12 months 16.3 % ; 19 - 24 months 14.4 % ) . Compared with uninfected women , HIV-positive women were more likely to use condoms in years 1 and 2 after delivery ( adjusted odds ratio ( AOR ) 1.72 , 95 % confidence interval ( CI ) 1.38 - 2.14 , p<0.001 ; AOR 1.61 , 95 % CI 1.15 - 2.25 , p=0.006 respectively ) . Compared with women with a flush toilet , those with a pit latrine were less likely to use condoms in years 1 and 2 ( AOR 0.22 , 95 % CI 01.7 - 0.28 , p<0.001 ; AOR 0.27 , 95 % CI 0.19 - 0.39 , p<0.001 ) . Older women were more likely to use condoms in the first postpartum year ( AOR 1.78 , 95 % CI 1.03 - 3.09 , p=0.040 ) . CONCLUSIONS More creative ways of promoting condoms and dual contraception need to be found if new HIV infections , in women and children , are to be prevented Output:	We found little innovation in the behavioral interventions . Since some of these studies were conducted , improvements in HIV treatment have influenced the fertility intentions of HIV-positive people .
MS2922	*TASK* the task is to summarize an input biomedical literature in six sentences *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 consecutive series of female patients with adolescent idiopathic scoliosis treated between 1968 and 1977 , either with distraction and fusion using Harrington rods ( n = 145 ) or with a brace ( n = 122 ) , were followed for at least 20 years after completion of the treatment . Objectives . To determine the long-term outcomes of childbearing and sexual life in women treated for adolescent idiopathic scoliosis , as compared with matched control subjects who did not have scoliosis . Summary of Background Data . The effect of pregnancy on curve progression is not established , and results are contradictory . Few reports exist on the social life ( marriage , childbearing , and sexual function ) of formerly treated individuals with scoliosis . Methods . In this study , 136 surgically treated women ( 94 % ) and 111 brace-treated women ( 91 % ) completed the Scoliosis Research Society (SRS)/MODEM ’s question naire concerning childbearing and sexual life as a part of an unbiased personal follow-up examination . Of these , 129 surgically treated and 105 brace-treated women also underwent a radiographic examination . The Cobb method was used to measure curve size in present and earlier examinations . An age-matched control group of 90 women was r and omly selected and subjected to the same examinations . Results . The mean age for all the groups was 40 years . Of the surgically treated and brace-treated women , 85 % were or had been married , as compared with 82 % of the control women . In the total cohort , 628 pregnancies had occurred . No significant mean difference existed between the groups in the number of children born ( 1.8 for the surgically treated , 1.9 for the brace-treated , and 2 for the control women ) ( P = 0.25 ) . The patients in the brace-treated group had a significantly higher mean age at first pregnancy ( 28 years ) than the control subjects ( 25.9 years ) ( P = 0.011 ) , whereas the age for the surgically treated women ( 26.6 years ) did not differ significantly from that for the brace-treated women . There were no significant differences between the groups in rates for low back pain ( 35 % for the surgically treated , 43 % for the brace-treated , and 28 % for the control group ) or for cesarean section ( 19 % for the surgically treated , 14 % for the brace-treated , and 18 % for the control group ) during the first pregnancy . The rate of vacuum extraction s was higher in the surgically treated group ( 16 % ) than in thecontrol group ( 5 % ) ( P = 0.036 ) or the brace-treated group(8 % ) . Limitation of sexual function from the back was admitted by 33 % of the surgically treated , 28 % of the brace-treated , and 15 % of the control women : surgically treated vs control subjects ( P = 0.0042 ) , brace-treated vs control subjects ( P = 0.026 ) , and brace-treated vs surgically treated subjects ( P = 0.57 , a nonsignificant difference ) . These limitations were largely because of difficulties participating physically in activities or self-consciousness about appearance . Pain was a minor reason for limitation . There was no correlation between progression of the major or lumbar curve and number of pregnancies , or between curve progression and age at first pregnancy . Conclusions . Patients treated for adolescent idiopathic scoliosis appeared to function well with regard to marital status and number of children . The scoliotic curve did not seem to increase as a result of childbearing . Minor problems occurred during pregnancy and delivery . Some patients , however , experienced a slight negative effect in their sexual life AIM Bracing is considered to be effective in the treatment of adolescent idiopathic scoliosis . The concept prevailing today includes an asymmetrical construction , mainly using a mechanical three-point system . We developed the new Sforzesco brace , based on the SPoRT concept ( Symmetric , Patient-oriented , Rigid , Three-dimensional , active ) . The aim of this study is to verify the results of this concept and brace , compared to three-point classical systems . METHODS We performed a prospect i ve , pair-controlled study . It was possible to match 15 patients , out of the first 18 consecutively treated with the Sforzesco brace ( Group SPoRT ) , with previous patients treated with the Lyon brace ( Group LY ) . SPoRT included 14.2+/-1.7 year old patients , with 47+/-7 degrees Cobb worst curves , and 11+/-4 degrees Bunnell ; LY included 13.6+/-1.6 year old patients , with 43+/-7 degrees Cobb and 12+/-5 degrees Bunnell . The brace had to be worn 23 h per day and patients were evaluated after 6 months both clinical ly and radiographically ( without the brace ) . Appropriate statistics were used . RESULTS At the baseline there were slight differences between the groups , with SPoRT worse than LY . All radiographic and clinical parameters decreased significantly with treatment in both groups , apart from thoracic Cobb degrees in LY . SPoRT had better results than LY ( P<0.05 ) radiographically ( worst curve -10+/-5 degrees vs -5+/-7 degrees , all curves -8+/-7 degrees vs -6+/-7 degrees ) , for sagittal profile ( distance from plumbline : T12 -6+/-9 mm vs + 2+/-8 and L3 -7+/-12 vs 0+/-10 ) and aesthetics of the shoulders ( 9 improved and 6 unchanged vs 5 and 8) and waists ( 10 improved and 5 unchanged vs 5 and 8) . Finally , clinical results in terms of patient recovery were better in SPoRT than LY ( 12 improved and 3 unchanged vs 8 and 5 ) . CONCLUSION When a new treatment is introduced , it is not possible to wait years ( end of therapy ) before verifying its utility , and in scoliosis bracing a short term study already gives very important clues . This study confirms the immediate efficacy of brace treatment ( even in such high degree cases ) whatever the brace concept used , with only 2 ( out of 30 ) progressed curves . In SPoRT we had no progressions , and obtained a statistically significant 80 % better radiographic results than LY in the worst scoliosis curve , and 40 % in the average of all curves , as well as improved aesthetics and sagittal profile ( that is crucial in scoliosis bracing ) . The Sforzesco brace should be used , and the SPoRT concept explored in the long term to verify if the classical three-point system should be totally ( or partially ) ab and oned Background Studies investigating the outcome of conservative scoliosis treatment differ widely with respect to the inclusion criteria used . This study has been performed to investigate the possibility to find useful inclusion criteria for future prospect i ve studies on physiotherapy ( PT ) . Material s and methods A PubMed search for outcome papers on PT was performed in order to detect study design s and inclusion criteria used . Results Real outcome papers ( start of treatment in immature sample s/end results after the end of growth ; controlled studies in adults with scoliosis with a follow-up of more than 5 years ) have not been found . Some papers investigated mid-term effects of exercises , most were retrospective , few prospect i ve and many included patient sample s with question able treatment indications . Conclusion There is no outcome paper on PT in scoliosis with a patient sample at risk for being progressive in adults or in adolescents followed from premenarchial status until skeletal maturity . However , papers on bracing are more frequently found and bracing can be regarded as evidence -based in the conservative management and rehabilitation of idiopathic scoliosis in adolescents Abstract . No results on long-term outcome in terms of health-related quality of life ( HRQL ) have previously been presented for patients treated for adolescent idiopathic scoliosis . A consecutive series of patients with adolescent idiopathic scoliosis , treated between 1968 and 1977 before the age of 21 , either with distraction and fusion using Harrington rods [ surgical treatment group ( ST ) , n=156 ; 145 females and 11 males ] or with a brace [ brace treatment group ( BT ) , n=127 ; 122 females and 5 males ] were followed at least 20 years after completion of the treatment . Ninety-four percent of ST and 91 % of BT patients filled in a question naire comprising the SF-36 , Psychological General Well-Being Index ( PGWB ) , Oswestry Disability Back Pain Question naire , parts of SRS/MODEM 'S question naire and study -specific questions concerning the treatment , as a part of an unbiased personal follow-up examination including radiography and clinical examination . An age- and sex-matched control group of 100 persons was r and omly selected and subjected to the same examinations . The results showed no differences in terms of sociodemographic data between the groups . Both ST and BT patients had a slightly , but significantly , reduced physical function using the SF-36 subscales , SF-36/Physical Component Summary ( PCS ) score as well as the Oswestry Disability Back Pain Question naire compared to the controls . Neither the mental subscales and the Mental Component Summary ( MCS ) score of SF-36 nor the PGWB index showed any significant difference between the groups . Forty-nine percent of ST , 34 % of BT and 15 % of controls admitted limitation of social activities due to their back [ P<0.001 ST vs controls , P=0.0010 BT vs controls , and n.s . ( P=0.024 ) ST vs BT ] , mostly due to difficulties with physical participation in activities or self-consciousness about appearance . Pain was a minor reason for limitation . No correlation was found between the outcome scores and curve size after treatment , curve type , total treatment time or age at completed treatment . Patients treated for adolescent idiopathic scoliosis were found to have approximately the same HRQL as the general population . A minority of the patients ( 4 % ) had a severely decreased psychological well-being , and a few ( 1.5 % ) were severely physically disabled due to the back Background Studies investigating the outcome of conservative scoliosis treatment differ widely with respect to the inclusion criteria used [ 1 ] . While the application of the SRS criteria for studies on bracing seem useful , there are no inclusion criteria for the investigation of physiotherapy alone . This study has been performed to investigate the possibility of useful inclusion criteria for future prospect i ve studies on physiotherapy ( PT ) BACKGROUND CONTEXT Evidence demonstrating the biomechanical effects of the Hueter-Volkmann principle on vertebral body growth in spinal deformities is lacking . Bracing a scoliotic curve should , in theory , unload the growth plates on the concave side of the vertebral bodies near the curve 's apex . Growth stimulation , leading to structural remodeling of the vertebral bodies , on the curve 's concave side may explain the improvement or lack of curve progression , as measured by Cobb angles , reported with successful brace management of adolescent idiopathic scoliosis ( AIS ) . PURPOSE To determine whether brace treatment stimulated asymmetric chondrogenesis in the apical three vertebral bodies . STUDY DESIGN A prospect i ve cohort of patients with AIS receiving brace treatment were followed from the initiation of brace treatment until skeletal maturity . Patients were then retrospectively divided into those with and without radiographic progression . This post hoc analysis was included to determine risk factors for curve progression . PATIENT SAMPLE Forty-one skeletally immature patients with AIS meeting criteria for brace treatment were followed until skeletal maturity . All patients were treated with thoracolumbosacral orthotics ( TLSOs ) . OUTCOME MEASURES The positional derotation of the TLSO on the spine was measured by comparing the initial radiograph with the first radiograph in a brace . The long-term structural changes of the vertebral bodies were determined by comparing the initial and final radiographs . Differences in initial radiographic parameters between the groups of patients with AIS with and without curve progression indicated predictive factors for successful brace treatment . METHODS Initial radiographic measurements were compared with those observed in a brace and those observed at final follow-up . The same analysis was retrospectively repeated comparing patients with AIS with and without radiographic progression . RESULTS Cobb measurements ( p=.0001 ) and concave-to-convex height ratios of the apical three vertebral bodies improved when the brace was initially applied ( p=.0035 ) . Structural remodeling or a rotational correction of the apical three vertebral bodies was appreciated only in patients with flexible curves ( p=.01 ) . CONCLUSION Brace application results in immediate positional derotations of the spine in patients with AIS . These positional derotations were maintained only in patients with flexible curves , at final follow-up . Brace treatment was not recommended in patients whose curves did not correct at least 20 % in a TLSO A prospect i ve study was carried out of the incidence and natural history of adolescent idiopathic scoliosis in 26,947 students . Data were obtained on 1,122 students with idiopathic scoliosis . The incidence of idiopathic scoliosis was 4.5 per cent . The female-to-male ratio was 1.25:1.0 over-all , but the ratio varied directly with the severity of the curve -- that is , 1:1 for curves of 6 to 10 degrees , and 5.4:1 for curves of more than 20 degrees . Progression of the curve was determined by a two-year follow-up of 603 patients . Progression was observed in 6.8 per cent of the students and in 15.4 per cent of the skeletally immature girls with scoliosis of more Output:	Short-term results of the surgical treatment of people with AIS demonstrate the ability of surgery to improve various outcome measures . MAIN RESULTS We did not identify any evidence comparing surgical to non-surgical interventions for AIS with severe curves of over 45 degrees .
MS2923	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Cardiopulmonary bypass ( CPB ) is widely regarded as an important contributor to renal failure , a well recognized complication following coronary artery surgery ( coronary artery bypass grafting ( CABG ) ) . Anecdotally off-pump coronary surgery ( OPCAB ) is considered renoprotective . We examine the extent of renal glomerular and tubular injury in low-risk patients undergoing either OPCAB or on-pump coronary artery bypass ( ONCAB ) . METHODS Forty low-risk patients with normal preoperative cardiac and renal functions awaiting elective CABG were prospect ively r and omized into those undergoing OPCAB ( n=20 ) and ONCAB ( n=20 ) . Glomerular and tubular injury were measured respectively by urinary excretion of microalbumin and retinol binding protein ( RBP ) indexed to creatinine ( Cr ) . Daily measurements were taken from admission to postoperative day 5 . Fluid balance , serum Cr and blood urea were also monitored . RESULTS No mortality or renal complication were observed . Both groups had similar demographic makeup , Parsonnet score , functional status and extent of coronary revascularization ( 2.1+/-1.0 vs. 2.5+/-0.7 grafts ; P=0.08 ) . Serum Cr and blood urea remained normal in both groups throughout the study . A significant and similar rise in urinary RBP : Cr occurred in both groups peaking on day 1 ( 3183+/-2534 vs. 4035+/-4079 ; P=0.43 ) before reapproximating baseline levels . These trends were also observed with urinary microalbumin : Cr ( 5.05+/-2.66 vs. 6.77+/-5.76 ; P=0.22 ) . Group B patients had a significantly more negative fluid balance on postoperative day 2 ( -183+/-1118 vs. 637+/-847 ml ; P=0.03 ) . CONCLUSIONS Although renal complication or serum markers of kidney dysfunction were absent , sensitive indicators revealed significant and similar injury to renal tubules and glomeruli following either OPCAB or ONCAB . These results suggest that avoidance of CPB does not offer additional renoprotection to patients at low risk of perioperative renal insult during CABG BACKGROUND Pulmonary dysfunction is still a major problem in coronary artery bypass grafting ( CABG ) . The purpose of this r and omized study was to determine the effect of different CABG techniques on pulmonary function . METHODS Fifty eight patients with severe obstructive pulmonary disease had elective isolated coronary surgery . The surgical methods for the patients with chronic obstructive pulmonary disease ( COPD ) were st and ard CABG in 18 patients ( group 1 ) , beating heart surgery in 19 patients ( group 2 ) , and minimally invasive direct coronary artery bypass grafting ( MIDCABG ) in 21 patients ( group 3 ) . RESULTS The earliest extubation time was from group 3 ( p < 0.001 ) . The average stay in the intensive care unit was significantly longer in group 1 ( 2.6 + /- 1.5 days ) than in groups 2 ( 1.4 + /- 0.8 days ) and 3 ( 1.1 + /- 0.8 days ) ( p < 0.05 ) . The most prevalent respiratory morbidity was atelectasis that developed in 6 patients from group 1 , in 2 patients from group 2 , and in 3 patients from group 3 . Forced expiratory volumes in 1 second ( FEV1 ) obtained in the second postoperative month were significantly lower than preoperative values only in group 1 ( p < 0.05 ) . Forced vital capacity ( FVC ) values were significantly lower than the preoperative values in all three groups ( p < 0.05 ) . CONCLUSIONS Off-pump bypass surgical procedures are more advantageous than on-pump methods for patients with COPD . These patients can be operated on using the beating heart technique or by using MIDCABG to prevent side effects of CPB on pulmonary function and effects of sternotomy BACKGROUND Coronary artery bypass surgery with cardiopulmonary bypass carries a significant risk of perioperative brain injury . At least 1 % to 5 % will suffer a stroke , and at 3-months postoperatively approximately 30 % are reported to have cognitive impairment assessed by neuropsychologic testing . In off-pump surgery cardiopulmonary bypass is not used and instrumentation on the ascending aorta is reduced . The main aim of this study was to assess if off-pump surgery reduces intraoperative cerebral embolization . METHODS This was a prospect i ve and r and omized study of two comparable groups with regard to age , sex , years of education , preoperative cognitive functioning , and surgical characteristics . Fifty-two patients ( 29 off-pump ) were monitored by the use of transcranial Doppler ultrasound for cerebral microembolization during surgery . Preoperative and postoperative clinical , cerebral magnetic resonance imaging , and neuropsychologic examinations were also carried out . RESULTS There was a significant reduction in the number of cerebral microemboli during off-pump compared with on-pump surgery ( 16.3 [ range 0 to 131 ] versus 90.0 [ range 15 to 274 ] , p < 0.0001 ) . No significant difference with regard to the incidence of neuropsychologic performance ( decline in 29 % off-pump , 35 % on-pump ) or neuroradiologic findings at 3 months was found , and there was no association between the number of cerebral microemboli and cognitive outcome . CONCLUSIONS This study clearly demonstrates that off-pump surgery leads to a reduction in intraoperative cerebral microembolization . A significant reduction in the number of off-pump patients with cognitive decline or ischemic brain lesions on cerebral magnetic resonance imaging could not be demonstrated in this relatively small patient population BACKGROUND Although no r and omised controlled trial has assessed the midterm effects of coronary-artery bypass surgery on the beating heart , this technique is being used in more and more patients . We did two r and omised trials to compare the short-term morbidity associated with off-pump and on-pump myocardial revascularisation . Our aim was to pool the results to assess midterm outcomes . METHODS From March , 1997 , to November , 1999 , we r and omly allocated 200 patients to off-pump and 201 to on-pump coronary surgery . In Beating Heart Against Cardioplegic Arrest Study ( BHACAS ) 1 , we excluded patients who had had myocardial infa rct ion in the past month or who required grafting of the circumflex artery distal to the first obtuse marginal branch . In BHACAS 2 , we included such patients . Primary outcomes were all-cause mortality and cardiac-related events at midterm follow-up ( 1 - 3 years ) . Analysis was by intention to treat . FINDINGS Analyses of combined data from both trials showed the following risk differences with off-pump compared with on-pump surgery : atrial fibrillation -25 % ( 95 % CI -33 % to -16 % ) ; chest infection -12 % ( -19 % to -5 % ) ; inotropic requirement -18 % ( -25 % to -10 % ) ; transfusion of red blood cells -31 % ( -41 to -21 ) ; and hospital stay longer than 7 days -13 % ( -21 to -5 ) . Mean follow-up was 25 0 months ( SD 9.1 ) for BHACAS 1 and 13.7 months ( 5 5 ) for BHACAS 2 . Four ( 2 % ) of 200 patients in the off-pump groups died from any cause , compared with seven ( 3 % ) of 201 in the on-pump group ( hazard ratio 0.57 , 95 % CI 0.17 - 1.96 ) . 33 ( 17 % ) of 200 patients in the off-pump group died or had a cardiac-related event , compared with 42 ( 21 % ) of 201 in the on-pump group ( 0.78 , 0 49 - 1.22 ) . INTERPRETATION Off-pump coronary surgery significantly lowers in-hospital morbidity without compromising outcome in the first 1 - 3 years after surgery compared with conventional on-pump coronary surgery BACKGROUND We investigated whether off-pump coronary artery bypass ( OPCAB ) surgery should be the procedure of choice in total arterial myocardial revascularization with composite grafts . METHODS We prospect ively enrolled 176 patients undergoing total arterial myocardial revascularization and assigned them at r and om to one of two groups : group 1 was composed of 88 patients undergoing coronary surgery with cardiopulmonary bypass ( CPB ) ; group 2 consisted of 88 patients receiving the OPCAB procedure . We excluded from this study patients with significant risk factors for CPB-related morbidity . Composite arterial grafts in Y-T shape were realized in three different configurations according to patients ' characteristics , coronary anatomy , and target stenosis . RESULTS There were no significant differences between the two groups in terms of preoperative characteristics and risk factors ( Euroscore : group 1 = 6.1 + /- 3.5 , group 2 = 6.6 + /- 3.8 ) . Mean number of anastomoses was similar in both groups ( group 1 = 2.8 + /- 0.8 , group 2 = 2.7 + /- 0.5 ) whereas mean mechanical ventilation time ( group 1 = 23 + /- 9 hours , group 2 = 9 + /- 4 hours ) , intensive care unit stay ( group 1 = 43 + /- 6 hours , group 2 = 22 + /- 8 hours ) , and postoperative stay ( group 1 = 7 + /- 3 days , group 2 = 5 + /- 2 days ) were significantly reduced in group 2 . Early mortality was 2.3 % in group 1 and 3.4 % in group 2 ( p = not significant ) . Major postoperative complications occurred similarly in the two groups ( atrial fibrillation : group 1 = 35.2 % , group 2 = 21.6 % ; myocardial infa rct ion : group 1 = 2.2 % , group 2 = 1.1 % ; stroke : group 1 = 2.2 % , group 2 = 0 % ; abdominal infa rct ion : group 1 = 3.4 % , group 2 = 0 % ) . At follow-up ( mean , 15 + /- 12 months ) no significant differences were observed in terms of survival free of any cardiac-related event ( group 1 = 94.3 % , group 2 = 96.5 % ; p = not significant ) . CONCLUSIONS Off-pump coronary artery surgery could be successfully used for total arterial grafting without compromising the completeness of revascularization . Avoidance of CPB significantly decreased mechanical ventilation support and length of intensive care unit and postoperative stay ; however in the absence of risk factors for cardiopulmonary bypass , off-pump coronary artery surgery did not improve early and midterm clinical outcome BACKGROUND The interpretation of the results of r and omized controlled trials ( RCTs ) has traditionally emphasized statistical significance rather than clinical importance . Our aim was to assess the quality of reporting of factors related to clinical importance in a sample of published RCTs . METHODS A r and om sample of 27 ( of a total of 266 ) RCTs published in 5 major medical journals over a 1-year period were review ed by 4 independent review ers for factors considered important in the interpretation of the clinical importance of study results : identification of a clearly defined primary outcome , reporting of the expected difference between groups used in the calculation of sample size ( the delta value ) and whether it was based on the minimal clinical ly important difference of the intervention , the statistical significance of the results , presentation of pertinent confidence intervals , and the authors ' interpretation of the clinical importance of the results . RESULTS Twenty-two of 27 ( 81 % ) articles explicitly reported a single primary outcome . Of the 20 articles that included a sample size calculation , 18 ( 90 % ) reported a delta value . Two of the 18 ( 11 % ) articles explicitly stated that the delta value was chosen to reflect the minimal clinical ly important difference of the intervention . For the primary outcomes , confidence intervals surrounding the point estimates of the efficacy of the interventions were reported in 11 of 27 ( 41 % ) studies . The study results were interpreted from the perspective of clinical importance in 20 of 27 ( 74 % ) of the articles . Of these 20 reports , 5 ( 25 % ) provided justification for their clinical interpretation of the results . INTERPRETATION Authors of RCTs published in major general medical and internal medicine journals do not consistently provide their own interpretation of the clinical importance of their results , and they often do not provide sufficient information to allow readers to make their own interpretation BACKGROUND There is increased interest in coronary artery bypass grafting ( CABG ) without cardiopulmonary bypass ( CPB ) , although the preservation of the myocardium under such circumstances has not been properly investigated . The aim of this r and omized study was to compare the changes in myocardial metabolism during CABG with and without CPB . METHODS Myocardial energy metabolism and tissue injury during CABG was monitored in a series of Output:	With GEE modelling , the reporting quality had a strong association with trial size , publication year , trial location and funding source , but not with the results and type of primary outcome .
MS2924	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Summary Use of the Chronic Pain Management Program was associated with significant decreases in pain‐related , functional , and mental health outcomes and an increase in pain knowledge . Abstract Internet‐based educational and therapeutic programs ( e‐health applications ) are becoming increasingly popular for a variety of psychological and physical disorders . We tested the efficacy of an online Chronic Pain Management Program , a comprehensive , fully self‐directed and self‐paced system that integrates social networking features and self‐management tools into an interactive learning environment . Of 305 adult participants ( 196 women , 109 men ) , a total of 162 individuals with chronic pain were r and omly assigned unsupervised access to the program for approximately 6 weeks ; 143 were assigned to the wait‐listed control group with treatment as usual . A comprehensive assessment was administered before the study and approximately 7 and 14 weeks thereafter . All recruitment , data collection , and participant involvement took place online . Participation was fully self‐paced , permitting the evaluation of program effectiveness under real‐world conditions . Intent‐to‐treat analysis that used linear growth models was used as the primary analytic tool . Results indicated that program utilization was associated with significant decreases in pain severity , pain‐related interference and emotional burden , perceived disability , catastrophizing , and pain‐induced fear . Further , program use led to significant declines in depression , anxiety , and stress . Finally , as compared to the wait‐listed control group , the experimental group displayed a significant increase in knowledge about the principles of chronic pain and its management . Study limitations are considered , including the recognition that not all persons with chronic pain are necessarily good c and i date s for self‐initiated , self‐paced , interactive learning Objective The aim of this study was to compare 2 self-help-based interventions ; a coping-oriented approach , applied relaxation ( AR ) and an acceptance-oriented approach , acceptance and commitment therapy ( ACT ) , for persons with chronic pain . Method This study is a r and omized control trial ( N=90 ) with a mixed between-within participants design with repeated measures . Interventions in both conditions comprised an initial face-to-face session , a 7-week manual-based self-help intervention including weekly therapist telephone support and a concluding face-to-face session . Outcome measures included satisfaction with life , depression , anxiety , acceptance of chronic pain , level of function , and pain intensity . Effects were measured at preintervention and postintervention and at 6 and 12 months after the end of intervention . Results The results show that the ACT condition increased their level of acceptance significantly compared with the AR condition . There was also a marginally significant interaction effect regarding satisfaction with life in which the ACT condition had improved in comparison to the AR condition . Further , the ACT condition reported a higher level of function and decreased pain intensity compared with the AR condition . Both conditions improved significantly regarding depression and anxiety . Conclusions A manual-based self-help intervention with weekly therapist support in an ACT format adds value to the treatment repertoire for persons suffering with chronic pain Background Patients with knee and /or hip osteoarthritis ( OA ) are less physically active than the general population , while the benefits of physical activity ( PA ) have been well documented . Based on the behavioral grade d activity treatment , we developed a Web-based intervention to improve PA levels in patients with knee and /or hip OA , entitled “ Join2move ” . The Join2move intervention is a self-paced 9-week PA program in which the patient ’s favorite recreational activity is gradually increased in a time-contingent way . Objective The aim of the study was to investigate whether a fully automated Web-based PA intervention in patients with knee and /or hip OA would result in improved levels of PA , physical function , and self-perceived effect compared with a waiting list control group . Methods The study design was a two-armed r and omized controlled trial which was not blinded . Volunteers were recruited via articles in newspapers and health-related websites . Eligibility criteria for participants were : ( 1 ) aged 50 - 75 years , ( 2 ) self-reported knee and /or hip OA , ( 3 ) self-reported inactivity ( 30 minutes of moderate PA , 5 times or less per week ) , ( 4 ) no face-to-face consultation with a health care provider other than general practitioners , for OA in the last 6 months , ( 5 ) ability to access the Internet weekly , and ( 6 ) no contra-indications to exercise without supervision . Baseline , 3-month , and 12-month follow-up data were collected through online question naires . Primary outcomes were PA , physical function , and self-perceived effect . In a subgroup of participants , PA was measured objective ly using accelerometers . Secondary outcomes were pain , fatigue , anxiety , depression , symptoms , quality of life , self-efficacy , pain coping , and locus of control . Results Of the 581 interested respondents , 199 eligible participants were r and omly assigned to the intervention ( n=100 ) or waiting list control group ( n=99 ) . Response rates of question naires were 84.4 % ( 168/199 ) after 3 months and 75.4 % ( 150/199 ) after 12 months . In this study , 94.0 % ( 94/100 ) of participants actually started the program , and 46.0 % ( 46/100 ) reached the adherence threshold of 6 out of 9 modules completed . At 3 months , participants in the intervention group reported a significantly improved physical function status ( difference=6.5 points , 95 % CI 1.8 - 11.2 ) and a positive self-perceived effect ( OR 10.7 , 95 % CI 4.3 - 26.4 ) compared with the control group . No effect was found for self-reported PA . After 12 months , the intervention group showed higher levels of subjective ( difference=21.2 points , 95 % CI 3.6 - 38.9 ) and objective PA ( difference=24 minutes , 95 % CI 0.5 - 46.8 ) compared with the control group . After 12 months , no effect was found for physical function ( difference=5 points , 95 % CI −1.0 to 11.0 ) and self-perceived effect ( OR 1.2 , 95 % CI 0.6 - 2.4 ) . For several secondary endpoints , the intervention group demonstrated improvements in favor of the intervention group . Conclusions Join2move result ed in changes in the desired direction for several primary and secondary outcomes . Given the benefits and its self-help format , Join2move could be a component in the effort to enhance PA in sedentary patients with knee and /or hip OA . Trial Registration The Netherl and s National Trial Register : NTR2483 ; http://www.trialregister.nl/trialreg/admin/ rct view.asp?TC=2483 ( Archived by WebCite at http://www.webcitation.org/67NqS6Beq ) Background It is estimated that 30 % of adults in the United States experience daily chronic pain . This results in a significant burden on the health care system , in particular primary care , and on the workplace . Chronic pain management with cognitive-behavioral psychological treatment is effective in reducing pain intensity and interference , health-related quality of life , mood , and return to work . However , the population of individuals with chronic pain far exceeds the population of therapists that can provide this care face-to-face . The use of tailored , Web-based interventions for the management of chronic pain could address limitations to access by virtue of its unlimited scalability . Objective To examine the effects of a tailored Web-based chronic pain management program on subjective pain , activity and work interference , quality of life and health , and stress . Methods Eligible participants accessed the online pain management program and informed consent via participating employer or health care benefit systems ; program participants who completed baseline , 1- , and 6-month assessment s were included in the study . Of the 645 participants , the mean age was 56.16 years ( SD 12.83 ) , most were female ( 447/645 , 69.3 % ) , and white ( 505/641 , 78.8 % ) . Frequent pain complaints were joint ( 249/645 , 38.6 % ) , back ( 218/645 , 33.8 % ) , and osteoarthritis ( 174/654 , 27.0 % ) . The online pain management program used evidence -based theories of cognitive behavioral intervention , motivational enhancement , and health behavior change to address self-management , coping , medical adherence , social support , comorbidities , and productivity . The program content was individually tailored on several relevant participant variables . Results Both pain intensity ( mean 5.30 , SD 2.46 ) , and unpleasantness ( mean 5.43 , SD 2.52 ) decreased significantly from baseline to 1-month ( mean 4.16 , SD 2.69 and mean 4.24 , 2.81 , respectively ) and 6-month ( mean 3.78 , SD 2.79 and mean 3.78 , SD 2.79 , respectively ) assessment s ( P<.001 ) . The magnitude of the 6-month effects were large . Trends for decreases in pain interference ( 36.8 % reported moderate or enormous interference ) reached significance at 6 months ( 28.9 % , P<.001 ) . The percentage of the sample reporting fair or poor quality of life decreased significantly from 20.6 % at baseline to 16.5 % at 6 months ( P=.006 ) . Conclusions Results suggest that the tailored online chronic pain management program showed promising effects on pain at 1 and 6 months posttreatment and quality of life at 6 months posttreatment in this naturalistic study . Further research is warranted to determine the significance and magnitude of the intervention ’s effects in a r and omized controlled trial BACKGROUND total knee arthroplasty is an effective means for relieving the symptoms associated with degenerative arthritis of the knee . Rehabilitation is a necessary adjunct to surgery and is important in regaining optimum function . Access to high- quality rehabilitation services is not always possible , especially for those who live in rural or remote areas . The aim of this study was to evaluate the equivalence of an Internet-based telerehabilitation program compared with conventional outpatient physical therapy for patients who have had a total knee arthroplasty . METHODS this investigation was a single-blinded , prospect i ve , r and omized , controlled noninferiority trial . Sixty-five participants were r and omized to receive a six-week program of outpatient physical therapy either in the conventional manner or by means of an Internet-based telerehabilitation program . The primary outcome measure was the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) measured at baseline and six weeks by a blinded independent assessor . Secondary outcomes included the Patient-Specific Functional Scale , the timed up- and -go test , pain intensity , knee flexion and extension , quadriceps muscle strength , limb girth measurements , and an assessment of gait . Noninferiority was assessed through the comparison of group differences with a noninferiority margin and with linear mixed model statistics . RESULTS baseline characteristics between groups were similar , and all participants had significant improvement on all outcome measures with the intervention ( p < 0.01 for all ) . After the six-week intervention , participants in the telerehabilitation group achieved outcomes comparable to those of the conventional rehabilitation group with regard to flexion and extension range of motion , muscle strength , limb girth , pain , timed up- and -go test , quality of life , and clinical gait and WOMAC scores . Better outcomes for the Patient-Specific Functional Scale and the stiffness subscale of the WOMAC were found in the telerehabilitation group ( p < 0.05 ) . The telerehabilitation intervention was well received by participants , who reported a high level of satisfaction with this novel technology . CONCLUSIONS the outcomes achieved via telerehabilitation at six weeks following total knee arthroplasty were comparable with those after conventional rehabilitation . LEVEL OF EVIDENCE therapeutic Level I. See Instructions to Authors for a complete description of levels of evidence Background Chronic pain , especially back pain , is a prevalent condition that is associated with disability , poor health status , anxiety and depression , decreased quality of life , and increased health services use and costs . Current evidence suggests that exercise is an effective strategy for managing chronic pain . However , there are few clinical programs that use generally available tools and a relatively low-cost approach to help patients with chronic back pain initiate and maintain an exercise program . Objective The objective of the study was to determine whether a pedometer-based , Internet-mediated intervention can reduce chronic back pain-related disability . Methods A parallel group r and omized controlled trial was conducted with 1:1 allocation to the intervention or usual care group . 229 veterans with nonspecific chronic back pain were recruited from one Department of Veterans Affairs ( VA ) health care system . Participants r and omized to the intervention received an uploading pedometer and had access to a website that provided automated walking goals , feedback , motivational messages , and social support through an e-community ( n=111 ) . Usual care participants ( n=118 ) also received the uploading pedometer but did not receive the automated feedback or have access to the website . The primary outcome was measured using the Rol and Morris Disability Question naire ( RDQ ) at 6 months ( secondary ) and 12 months ( primary ) with a difference in mean scores of at least 2 considered clinical ly meaningful . Both a complete case and all case analysis , using linear mixed effects models , were conducted to assess differences between study groups at both time points . Results Baseline mean RDQ scores were greater than 9 in both groups . Primary outcome data were provided by approximately 90 % of intervention and usual care participants at both 6 and 12 months . At 6 months , average R Output:	RESULTS Across modalities , the existing evidence suggests that technology-assisted psychological interventions are efficacious for improving self-management of chronic pain in adults . All modalities have been shown to provide benefit and no clearly superior modality has emerged .
MS2925	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objective A focus on bacterial contamination has limited many studies of water service delivery in slums , with diarrheal illness being the presumed outcome of interest . We conducted a mixed methods study in a slum of 12,000 people in Mumbai , India to measure deficiencies in a broader array of water service delivery indicators and their adverse life impacts on the slum ’s residents . Methods Six focus group discussion s and 40 individual qualitative interviews were conducted using purpose ful sampling . Quantitative data on water indicators — quantity , access , price , reliability , and equity — were collected via a structured survey of 521 households selected using population -based r and om sampling . Results In addition to negatively affecting health , the qualitative findings reveal that water service delivery failures have a constellation of other adverse life impacts — on household economy , employment , education , quality of life , social cohesion , and people ’s sense of political inclusion . In a multivariate logistic regression analysis , price of water is the factor most strongly associated with use of inadequate water quantity ( ≤20 liters per capita per day ) . Water service delivery failures and their adverse impacts vary based on whether households fetch water or have informal water vendors deliver it to their homes . Conclusions Deficiencies in water service delivery are associated with many non-health-related adverse impacts on slum households . Failure to evaluate non-health outcomes may underestimate the deprivation result ing from inadequate water service delivery . Based on these findings , we outline a multidimensional definition of household “ water poverty ” that encourages policymakers and research ers to look beyond evaluation of water quality and health . Use of multidimensional water metrics by governments , slum communities , and research ers may help to ensure that water supplies are design ed to advance a broad array of health , economic , and social outcomes for the urban poor Background People living with HIV/AIDS have substantially greater need for water , sanitation , and hygiene . Encouraging hygiene education for People Living with HIV/AIDS in home based care services and additional support for the provision of water , sanitation , and hygiene services is recommended . Methods A cross-sectional study was carried during 2009 to assess water , sanitation status and hygiene practice s and associated factors among People Living with HIV/AIDS in home based care services in Gondar city of Ethiopia . A systematic r and om sampling was used to select study subjects from 900 Home Based Care clients of People Living HIV/AIDS in Gondar city . Data was collected from 296 People Living with HIV/AIDS from two NGO ’s in the city . For in-depth interview , four different categories were participated . Logistic regression and thematic framework analysis were performed for quantitative and qualitative part respectively . Results Two hundred ninety four subjects ( 72.8 % ( 214 ) females and 27.2 % ( 80 ) males ) were studied . The mean age was 35.8 ± 8.7 years . In the study , 42.9 % ( 126 ) of the households have unimproved water status , 67 % ( 197 ) of the households have unimproved sanitation status , and 51.7 % ( 152 ) of the households have poor hygienic practice . Diarrhoea with water status ; educational status and latrine availability with sanitation status ; and h and washing device availability and economical reasons for the affordability of soap with hygienic practice were significantly associated . Economical reasons and hygiene education were factors that affect water , sanitation , and hygienic practice . Stigma and discrimination were minimized as a factor in the study area . Conclusions There is high burden of water , sanitation and hygiene in people living HIV/AIDS in home based care services . Encouraging hygiene education for people living HIVAIDS in home based care services and additional support for the provision of water , sanitation , and hygiene services is recommended Background Governments , multinational organisations , and charities have commenced the distribution of sanitary products to address current deficits in girls ’ menstrual management . The few effectiveness studies conducted have focused on health and education outcomes but have failed to provide quantitative assessment of girls ’ preferences , experiences of absorbents , and comfort . Objectives of the study were , first , to quantitatively describe girls ’ experiences with , and ratings of reliability and acceptability of different menstrual absorbents . Second , to compare ratings of freely-provided reusable pads ( AFRIpads ) to other existing methods of menstrual management . Finally , to assess differences in self-reported freedom of activity during menses according to menstrual absorbent . Methods Cross-sectional , secondary analysis of data from the final survey of a controlled trial of reusable sanitary pad and puberty education provision was undertaken . Participants were 205 menstruating schoolgirls from eight schools in rural Ug and a. 72 girls who reported using the intervention-provided reusable pads were compared to those using existing improvised methods ( predominately new or old cloth ) . Results Schoolgirls using reusable pads provided significantly higher ratings of perceived absorbent reliability across activities , less difficulties changing absorbents , and less disgust with cleaning absorbents . There were no significant differences in reports of outside garment soiling ( OR 1.00 95%CI 0.51–1.99 ) , or odour ( 0.84 95%CI 0.40–1.74 ) during the last menstrual period . When girls were asked if menstruation caused them to miss daily activities there were no differences between those using reusable pads and those using other existing methods . However , when asked about activities avoided during menstruation , those using reusable pads participated less in physical sports , working in the field , fetching water , and cooking . Conclusions Reusable pads were rated favourably . This translated into some benefits for self-reported involvement in daily activities , although reports of actual soiling and missing activities due to menstruation did not differ . More research is needed comparing the impact of menstrual absorbents on girls ’ daily activities , and validating outcome measures for menstrual management research The lifting and carrying of loads in agriculture on small l and holdings are unavoidable . Rural communities often lack access to appropriate technologies which may result in various health hazards . The objective was to study gender participation in agricultural activities involving manual material h and ling tasks , to assess MSDs experienced in various MMH tasks and to evaluate traditional method and design ed technology . The study was conducted on 100 agricultural workers . Data on gender participation in MMH tasks in household , animal husb and ry and agriculture and result ing MSDs was gathered . Pre and post assessment of technology intervention was done for NIOSH Lifting Index , QEC , and RPE . The results revealed greater susceptibility of females to musculoskeletal problems in most of the household and animal husb and ry tasks . The h and trucks design ed were pushing type with power grasp h and le . The respondents were advised to carry 5 kg of weight per lift instead of lifting more weight in one lift/minute while filling the h and truck . By decreasing the weight and increasing the number of lifts per minute the respondents were seen falling in green zone indicating significant reduction in NIOSH lifting index . QEC scores concluded that for filling the h and truck 5 kg of weight should be carried to keep the exposure level low This paper examines the impact of water fetching by women and the quality of water during periods of water scarcity on the health of women in the Kumasi metropolitan area . A sample of 210 women drawn using systematic r and om procedure is used for the study . Formal interview is the main instrument used . The survey has established that income , quality of water , hours spent fetching water during scarcity and age are the main factors influencing women 's health in the metropolis during water scarcity . In both the core and periphery , the water-related problem influencing health is hours spent fetching water during scarcity . An empirical model on water needs and women 's health has emerged from the survey . Recommendations have been made on strategies to ensure regular volume of surface water , effective management of scarce water re sources with the participation of women , and ensuring gender equity in domestic services The use of self-assessed health status ( SAHS ) as a measure of health is common in empirical research . We analyse a unique Australian survey in which a r and om sub- sample of respondents answer a st and ard self-assessed health question twice-before and after an additional set of health related questions . A total of 28 % of respondents change their reported health status . Response reliability is related to age , income and occupation . We also compare the responses of these individuals to other respondents who are queried only once , to isolate effects of question order and mode of administration We used a community engagement approach to develop a One Health profile of an agro-pastoralist population at the interface of wildlife areas in eastern South Africa . Representatives from 262 r and omly-selected households participated in an in-person , cross-sectional survey . Questions were design ed to ascertain the participants ' knowledge , attitudes , and practice s with regard to human health , domestic animal health , and natural re sources including wildlife and water . Surveys were conducted within four selected villages by a team of trained surveyors and translators over four weeks in July-August 2013 . Questions were a combination of multiple choice ( single answer ) , multiple selection , open-ended , and Likert scale . The study found that nearly three-quarters of all households surveyed reported owning at least one animal ( 55 % owned chickens , 31 % dogs , 25 % cattle , 16 % goats , 9 % cats , and 5 % pigs ) . Among the animal-owning respondents , health concerns identified included dissatisfaction with government-run cattle dip facilities ( 97 % ) and frequent morbidity and mortality of chickens that had clinical signs consistent with Newcastle disease ( 49 % ) . Sixty-one percent of participants believed that diseases of animals could be transmitted to humans . Ninety-six percent of respondents desired greater knowledge about animal diseases . With regard to human health issues , the primary barrier to health care access was related to transportation to/from the community health clinics . Environmental health issues revealed by the survey included disparities by village in drinking water reliability and frequent domiciliary rodent sightings positively associated with increased household size and chicken ownership . Attitudes towards conservation were generally favorable ; however , the community demonstrated a strong preference for a dichotomous approach to wildlife management , one that separated wildlife from humans . Due to the location of the community , which neighbors the Great Limpopo Transfrontier Conservation Area , and the livestock-dependent lifestyle of the re source -poor inhabitants , a One Health approach that takes into consideration the interconnectedness of human , animal , and environmental health is necessary . The community profile described in this study provides a foundation for health research and planning initiatives that are driven by community engagement and consider the multitude of factors affecting health at the human-domestic animal-wildlife interface . Furthermore , it allows for the determination and quantification of the linkages between human , animal , and environmental health OBJECT The Hoffmann sign is commonly used in clinical practice to assess cervical spine disease . It is unknown whether the sign correlates with the severity of myelopathy , and no consensus exists regarding the significance of a positive sign in asymptomatic individuals . METHODS In a retrospective review of cervical spine surgeries for myelopathy due to cervical spondylosis , ossification of the posterior longitudinal ligament , or disc herniation performed at a tertiary center , the authors compiled data on the presence of hyperreflexia , the Hoffmann and Babinski signs , and modified Japanese Orthopaedic Association ( mJOA ) scale scores . Then , in a prospect i ve evaluation , new patients with lumbar spine complaints were examined for the presence of a Hoffmann sign , and , if present , a cervical MR imaging study was assessed for cord compression . RESULTS Of the 225 surgically treated patients , a Hoffmann sign occurred in 68 % , hyperreflexia in 60 % , and a Babinski sign in 33 % . In patients with milder disability ( mJOA Scores 14 - 16 ) , the Hoffmann sign was present in 46 % , whereas a Babinski sign occurred in 10 % ; in those with severe myelopathy and mJOA scores of < or = 10 , the Hoffmann sign was present in 81 % and the Babinski sign in 83 % . Of 290 patients presenting exclusively with lumbar spine-related complaints , 36 ( 12 % ) had a positive Hoffmann sign . Magnetic resonance imaging demonstrated spinal cord compression in 91 % when the sign was present bilaterally and 50 % when positive unilaterally . CONCLUSIONS In patients surgically treated for cervical myelopathy , the Hoffmann sign is more prevalent and more likely to be seen in individuals with less severe neurological deficits than the Babinski sign . In patients with lumbar symptoms , a bilateral Hoffmann sign was a highly sensitive marker for occult cervical cord compression , whereas a unilateral Hoffmann sign correlated with similar disease in about one-half of patients Output:	Overall , the studies suggest that water carriage is associated with negative aspects of the water carriers ' health . There is moderate quantitative and strong qualitative evidence that water carriage is associated with pain , fatigue , perinatal health problems and violence against vulnerable people , and inconclusive evidence of an association with stress or self-reported mental health and general health status .
MS2926	*TASK* the task is to summarize an input biomedical literature in six sentences *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 prevalence of type 2 diabetes ( T2D ) is seen in some immigrant groups in Western countries , particularly in those from the Indian subcontinent . Our aims were to increase the physical activity ( PA ) level in a group of Pakistani immigrant men , and to see whether any increase was associated with reduced serum glucose and insulin concentrations . The intervention was developed in collaboration with the Pakistani community . It used a social cognitive theory framework and consisted of structured supervised group exercises , group lectures , individual counselling and telephone follow-up . One- hundred and fifty physically inactive Pakistani immigrant men living in Oslo , Norway , were r and omised to either a control group or an intervention group . The 5-month intervention focused on increasing levels of PA , which were assessed by use of accelerometer ( Actigraph MTI 7164 ) recordings . Risk of diabetes was assessed by serum glucose and insulin concentrations determined in a fasted state , and after an oral glucose tolerance test ( OGTT ) . ANCOVA was used to assess differences between groups . There was a mean difference in PA between the two groups of 49 counts per minute per day , representing a 15 % ( 95 % CI = 8.7–21.2 ; P = 0.01 ) higher increase in total PA level in the intervention group than in the control group . Insulin values taken 2 h after an OGTT were reduced in the intervention group by 27 % ( 95 % CI = 18.9–35.0 ; P = 0.02 ) more than those in the control group . There were no differences in fasting or postpr and ial glucose values between the groups at the follow-up test . This type of intervention can increase PA and reduce serum insulin in Pakistani immigrant men , thereby presumably reducing their risk of T2D OBJECTIVES To investigate the acceptability and feasibility of using short message services ( SMS ) via cell phones to ensure adherence to management prescriptions by diabetic patients . METHODS Type 2 diabetic patients with 5 or more years of diabetes and having HbA1c between 7.0 % to 10 % were r and omized to the control arm ( n = 105 ) to receive st and ard care and to the intervention arm ( SMS , n = 110 ) . Messages in English on principles of diabetes management were sent once in 3 days , the contents and frequencies varied as per the patients ' preferences . The study duration was 1 year . All participants were advised to report for quarterly clinic visits . A comparative assessment of the clinical , biochemical and anthropometric outcomes was made among the groups at the annual visit . RESULTS Annual review was possible in 71 % of intervention group and 63 % of control group . SMS was acceptable to the patients and the median number requested was 2 per week . HbA1c and plasma lipids improved significantly in the SMS group . CONCLUSIONS The pilot study showed that frequent communication via SMS was acceptable to diabetic patients and it helped to improve the health outcomes Migrant mortality does not conform to a single pattern of convergence towards prevalence rates in the host population . To underst and better how migrant mortality develops , it is necessary to further investigate how the underlying behavioural determinants change following migration . We studied whether the prevalence of behavioural risk factors over two generations of Turkish and Moroccan migrants converge towards the prevalence rates in the Dutch population . From a r and om sample from the population register of Amsterdam , 291 Moroccan and 505 Turkish migrants , aged 15–30 , participated in a structured interview that included questions on smoking , alcohol consumption , physical inactivity and weight/height . Data from the Dutch population were available from Statistics Netherl and s. By calculating age-adjusted Odds Ratio ’s , prevalence rates among both generations were compared with prevalence rates in the host population for men and women separately . We found indications of convergence across generations towards the prevalence rates in the host population for smoking in Turkish men , for overweight in Turkish and Moroccan women and for physical inactivity in Turkish women . Alcohol consumption , however , remained low in all subgroups and did not converge towards the higher rates in the host population . In addition , we found a reversed trend among Turkish women regarding smoking : the second generation smoked significantly more , while the first generation did not differ from ethnic Dutch . In general , behavioural risk factors in two generations of non-Western migrants in the Netherl and s seem to converge towards the prevalence rates in the Dutch population . However , some subgroups and risk factors showed a different pattern This study used an experimental , pretest-posttest control group repeated measures design to evaluate the effectiveness of a community-based culturally appropriate lifestyle intervention program to reduce the risk for type 2 diabetes ( T2DM ) among Gujarati Asian Indians ( AIs ) in an urban community in the US . Participants included 70 adult AIs in the greater Houston metropolitan area . The primary outcomes were reduction in weight and hemoglobin A1c ( HbA1c ) and improvement in physical activity . Participants were screened for risk factors and r and omly assigned to a 12-week group-based lifestyle intervention program ( n = 34 ) or a control group ( n = 36 ) that received st and ard print material on diabetes prevention . Participants also completed clinical measures and self-reported question naires about physical activity , social , and lifestyle habits at 0 , 3 , and 6 months . No significant baseline differences were noted between groups . While a significant decline in weight and increase in physical activity was observed in all participants , the intervention group lowered their HbA1c ( p < 0.0005 ) and waist circumference ( p = 0.04 ) significantly as compared to the control group . Findings demonstrated that participation in a culturally tailored , lifestyle intervention program in a community setting can effectively reduce weight , waist circumference , and HbA1c among Gujarati AIs living in the US Type 2 diabetes is extremely common in South Asians , e.g. in men from Pakistani and Indian population s it is about three times as likely as in the general population in Engl and , despite similarities in body mass index . Lifestyle interventions reduce the incidence of diabetes . Trials in Europe and North America have not , however , reported on the impact on South Asian population s separately or provided the details of their cross-cultural adaptation processes . Prevention of diabetes and obesity in South Asians ( PODOSA ) is a r and omized , controlled trial in Scotl and of an adapted , lifestyle intervention aim ed at reducing weight and increasing physical activity to reduce type 2 diabetes in Indians and Pakistanis . The trial was adapted from the Finnish Diabetes Prevention Study . We describe , reflect on and discuss the following key issues : The core adaptations to the trial design , particularly the delivery of the intervention in homes by dietitians rather than in clinics . The use of both a multilingual panel and professional translators to help translate and /or develop material s. The processes and challenges of phonetic translation . How intervention re sources were adapted , modified , newly developed and translated into Urdu and Gurmukhi ( written Punjabi ) . The insights gained in PODOSA ( including time pressures on investigators , imperfections in the adaptation process , the power of verbal rather than written information , the utilization of English and the mother-tongue language s simultaneously by participants and the costs ) might help the research community , given the challenge of health promotion in multi-ethnic , urban societies Background To our knowledge , no studies have aim ed at improving the PA level in south Asian immigrant men residing in Western countries , and few studies have considered the relevance of SCT constructs to the PA behaviour of this group in the long term . The observed low physical activity ( PA ) level among south Asian immigrants in Western countries may partly explain the high prevalence of cardiovascular diseases ( CVD ) and type 2 diabetes ( T2D ) in this group . We have shown previously in a r and omised controlled trial , the Physical Activity and Minority Health study ( PAMH ) that a social cognitive based intervention can beneficially influence PA level and subsequently reduce waist circumference and insulin resistance in the short-term . In an extended follow-up of the PAMH study : we aim ed 1 ) to determine if the intervention produced long-term positive effects on PA level six months after intervention ( follow-up 2 ( FU2 ) ) , and 2 ) to identify the social cognitive mediators of any intervention effects . Methods Physically inactive Pakistani immigrant men ( n = 150 ) who were free of CVD and T2D were r and omly assigned to a five months PA intervention or a control group . Six months after the intervention ended , we telephoned all those who attended FU1 and invited them for a second follow-up test ( FU2 ) ( n = 133 ) . PA was measured using ActiGraph accelerometers . Statistical differences between groups were determined by use of ANCOVA . Results Significant differences ( baseline to FU2 ) between the groups were found for all PA variables ( e.g. , total PA level , sedentary time , PA intensity ) . Support from family and outcome expectancies increased more in the intervention group compared with the control group . Self-efficacy did not differ significantly between groups . Conclusions Our results show that a multi component PA programme can increase PA over the short and long term in a group of immigrant Pakistani men . However , we could not identify the factors that mediated these changes in PA . Protocol ID07112001326 , NCT ID : BACKGROUND Type 2 diabetes can often be prevented by lifestyle modification ; however , successful lifestyle intervention programmes are labour intensive . Mobile phone messaging is an inexpensive alternative way to deliver educational and motivational advice about lifestyle modification . We aim ed to assess whether mobile phone messaging that encouraged lifestyle change could reduce incident type 2 diabetes in Indian Asian men with impaired glucose tolerance . METHODS We did a prospect i ve , parallel-group , r and omised controlled trial between Aug 10 , 2009 , and Nov 30 , 2012 , at ten sites in southeast India . Working Indian men ( aged 35 - 55 years ) with impaired glucose tolerance were r and omly assigned ( 1:1 ) with a computer-generated r and omisation sequence to a mobile phone messaging intervention or st and ard care ( control group ) . Participants in the intervention group received frequent mobile phone messages compared with controls who received st and ard lifestyle modification advice at baseline only . Field staff and participants were , by necessity , not masked to study group assignment , but allocation was concealed from laboratory personnel as well as principal and co-investigators . The primary outcome was incidence of type 2 diabetes , analysed by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00819455 . RESULTS We assessed 8741 participants for eligibility . 537 patients were r and omly assigned to either the mobile phone messaging intervention ( n=271 ) or st and ard care ( n=266 ) . The cumulative incidence of type 2 diabetes was lower in those who received mobile phone messages than in controls : 50 ( 18 % ) participants in the intervention group developed type 2 diabetes compared with 73 ( 27 % ) in the control group ( hazard ratio 0·64 , 95 % CI 0·45 - 0·92 ; p=0·015 ) . The number needed to treat to prevent one case of type 2 diabetes was 11 ( 95 % CI 6 - 55 ) . One patient in the control group died suddenly at the end of the first year . We recorded no other serious adverse events . INTERPRETATION Mobile phone messaging is an effective and acceptable method to deliver advice and support towards lifestyle modification to prevent type 2 diabetes in men at high risk . FUNDING The UK India Education and Research Initiative , the World Diabetes Foundation Background In low/middle income countries like India , diabetes is prevalent and health care access limited . Most adults have a mobile phone , creating potential for mHealth interventions to improve public health . To examine the feasibility and initial evidence of effectiveness of mDiabetes , a text messaging program to improve diabetes risk behaviors , a global nonprofit organization ( Arogya World ) implemented mDiabetes among one million Indian adults . Objective A prospect i ve , parallel cohort design was applied to examine whether mDiabetes improved fruit , vegetable , and fat intakes and exercise . Methods Intervention participants were r and omly selected from the one million Nokia subscribers who elected to opt in to mDiabetes . Control group participants were r and omly selected from non-Nokia mobile phone subscribers . mDiabetes participants received 56 text messages in their choice of 12 language s over 6 months ; control participants received no contact . Messages were design ed to motivate improvement in diabetes risk behaviors and increase awareness about the causes and complications of diabetes . Participant health behaviors ( exercise and fruit , vegetable , and fat intake ) were assessed between 2012 and 2013 via telephone surveys by blinded assessors at baseline and 6 months later . Data were cleaned and analyzed in 2014 and 2015 . Results 982 participants in the intervention group and 943 in the control group consented to take the phone survey at baselne . At the end of the 6-month period , 611 ( 62.22 % ) in the intervention and 632 ( 67.02 % ) in the control group completed the follow-up telephone survey . Participants receiving texts demonstrated greater improvement in a health behavior composite score over 6 months , compared with those who received no messages F(1 , 1238 ) = 30.181 , P<.001 , 95 % CI , 0.251 - 0.531 . Fewer intervention participants demonstrated health behavior decline compared with controls . Improved fruit , vegetable , and fat consumption ( P<.01 ) but not exercise were observed in those receiving messages , as compared with controls . Conclusions A text messaging intervention was feasible and showed initial evidence of effectiveness in improving diab Output:	The findings show that involving the target community in developing culturally appropriate interventions appears to be important in their acceptability , delivery and uptake . Using community-based participation in intervention planning , evaluation and research appears to produce culturally and linguistically tailored interventions that address core values , attitudes , beliefs and norms , and encourage participation in PA . Furthermore , the use of community health workers and underpinning the interventions with a psychological theory show promise in increasing PA uptake .
MS2927	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Many patients show no or incomplete responses to current pharmacological or psychological therapies for depression . Here we explored the feasibility of a new brain self-regulation technique that integrates psychological and neurobiological approaches through neurofeedback with functional magnetic resonance imaging ( fMRI ) . In a proof-of-concept study , eight patients with depression learned to upregulate brain areas involved in the generation of positive emotions ( such as the ventrolateral prefrontal cortex ( VLPFC ) and insula ) during four neurofeedback sessions . Their clinical symptoms , as assessed with the 17-item Hamilton Rating Scale for Depression ( HDRS ) , improved significantly . A control group that underwent a training procedure with the same cognitive strategies but without neurofeedback did not improve clinical ly . R and omised blinded clinical trials are now needed to exclude possible placebo effects and to determine whether fMRI-based neurofeedback might become a useful adjunct to current therapies for depression For most people , adolescence is synonymous with emotional turmoil and it has been shown that early difficulties with emotion regulation can lead to persistent problems for some people . This suggests that intervention during development might reduce long-term negative consequences for those individuals . Recent research has highlighted the suitability of real-time fMRI-based neurofeedback ( NF ) in training emotion regulation ( ER ) networks in adults . However , its usefulness in directly influencing plasticity in the maturing ER networks remains unclear . Here , we used NF to teach a group of 17 7–16 year-olds to up-regulate the bilateral insula , a key ER region . We found that all participants learned to increase activation during the up-regulation trials in comparison to the down-regulation trials . Importantly , a subsequent Granger causality analysis of Granger information flow within the wider ER network found that during up-regulation trials , bottom-up driven Granger information flow increased from the amygdala to the bilateral insula and from the left insula to the mid-cingulate cortex , supplementary motor area and the inferior parietal lobe . This was reversed during the down-regulation trials , where we observed an increase in top-down driven Granger information flow to the bilateral insula from mid-cingulate cortex , pre- central gyrus and inferior parietal lobule . This suggests that : 1 ) NF training had a differential effect on up-regulation vs down-regulation network connections , and that 2 ) our training was not only superficially concentrated on surface effects but also relevant with regards to the underlying neurocognitive bases . Together these findings highlight the feasibility of using NF in children and adolescents and its possible use for shaping key social cognitive networks during development If an individual can learn to directly control activation of localized regions within the brain , this approach might provide control over the neurophysiological mechanisms that mediate behavior and cognition and could potentially provide a different route for treating disease . Control over the endogenous pain modulatory system is a particularly important target because it could enable a unique mechanism for clinical control over pain . Here , we found that by using real-time functional MRI ( rtfMRI ) to guide training , subjects were able to learn to control activation in the rostral anterior cingulate cortex ( rACC ) , a region putatively involved in pain perception and regulation . When subjects deliberately induced increases or decreases in rACC fMRI activation , there was a corresponding change in the perception of pain caused by an applied noxious thermal stimulus . Control experiments demonstrated that this effect was not observed after similar training conducted without rtfMRI information , or using rtfMRI information derived from a different brain region , or sham rtfMRI information derived previously from a different subject . Chronic pain patients were also trained to control activation in rACC and reported decreases in the ongoing level of chronic pain after training . These findings show that individuals can gain voluntary control over activation in a specific brain region given appropriate training , that voluntary control over activation in rACC leads to control over pain perception , and that these effects were powerful enough to impact severe , chronic clinical pain Real‐time functional magnetic resonance imaging ( rtfMRI ) is a novel technique that has allowed subjects to achieve self‐regulation of circumscribed brain regions . Despite its anticipated therapeutic benefits , there is no report on successful application of this technique in psychiatric population s. The objectives of the present study were to train schizophrenia patients to achieve volitional control of bilateral anterior insula cortex on multiple days , and to explore the effect of learned self‐regulation on face emotion recognition ( an extensively studied deficit in schizophrenia ) and on brain network connectivity . Nine patients with schizophrenia were trained to regulate the hemodynamic response in bilateral anterior insula with contingent rtfMRI neurofeedback , through a 2‐weeks training . At the end of the training stage , patients performed a face emotion recognition task to explore behavioral effects of learned self‐regulation . A learning effect in self‐regulation was found for bilateral anterior insula , which persisted through the training . Following successful self‐regulation , patients recognized disgust faces more accurately and happy faces less accurately . Improvements in disgust recognition were correlated with levels of self‐activation of right insula . RtfMRI training led to an increase in the number of the incoming and outgoing effective connections of the anterior insula . This study shows for the first time that patients with schizophrenia can learn volitional brain regulation by rtfMRI feedback training leading to changes in the perception of emotions and modulations of the brain network connectivity . These findings open the door for further studies of rtfMRI in severely ill psychiatric population s , and possible therapeutic applications . Hum Brain Mapp , 2013 . © 2011 Wiley Periodicals , OBJECTIVE This study examined the effect of motivation as a possible psychological influencing variable on P300 amplitude and performance in a brain-computer interface ( BCI ) controlled by event-related potentials ( ERP ) . METHODS Participants were instructed to copy spell a sentence by attending to cells of a r and omly flashing 7 * 7 matrix . Motivation was manipulated by monetary reward . In two experimental groups participants received 25 ( N=11 ) or 50 ( N=11 ) Euro cent for each correctly selected character ; the control group ( N=11 ) was not rewarded . BCI performance was defined as the overall percentage of correctly selected characters ( correct response rate = CRR ) . RESULTS Participants performed at an average of 99 % . At electrode location Cz the P300 amplitude was positively correlated to self-rated motivation . The P300 amplitude of the most motivated participants was significantly higher than that of the least motivated participants . Highly motivated participants were able to communicate correctly faster with the ERP-BCI than less motivated participants . CONCLUSIONS Motivation modulates the P300 amplitude in an ERP-BCI . SIGNIFICANCE Motivation may contribute to variance in BCI performance and should be monitored in BCI setting Sixteen subjects naive to biofeedback learned lateralised interhemispheric control of slow cortical potentials ( SCPs ) across electrode sites F3-F4 during three sessions of visual electroencephalograph ( EEG ) biofeedback . Subjects were required to generate slow negativity shifts either towards the left or the right hemisphere in sixty pseudor and omly ordered trials per session . Group 1 ( n = 8) were told to use emotional strategies in the task ( positive emotions for left hemisphere activation , negative emotion for right hemisphere activation ) , group 2 received no guidance . Both groups received feedback in the form of an on-screen rocket-ship , initially central ly placed , which rose to indicate an increase in left hemisphere negativity ( relative to the right hemisphere ) and fell to indicate an increase in right hemisphere negativity ( relative to the left hemisphere ) . A 2 x 3 x 3 x 2 ANOVA ( group x session x block x trial ) showed no performance differences between the strategy and no strategy groups . Both groups learned to produce correct direction shifts in the final third of each session during both trial types ( P < 0.001 ) . The no strategy group showed a particularly strong within session learning effect ( P < 0.0037 ) with poor performance in the early part of the sessions , and strong shifts at the end . Subjects high on withdrawal showed stronger rightward shifts in keeping with right hemisphere involvement in behavioural withdrawal . This is the first demonstration of self regulation of interhemispheric frontal asymmetry Output:	Several main categories emerged : Attentional variables appear to be of importance to both performance and learning , motivational factors and mood have been implicated as moderate predictors of success , while personality factors have mixed findings . Attention , motivation , mood and other factors affect neurofeedback success . Attention is consistently found to be crucial for efficient neurofeedback learning . Mood and Motivation are moderate predictors of neurofeedback success .
MS2928	*TASK* the task is to summarize an input biomedical literature in six sentences *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 study was to evaluate the phosphate-binding efficacy , side effects , and cost of therapy of calcium ketoglutarate granulate as compared with calcium carbonate tablets in patients on chronic hemodialysis . The study design used was a r and omized , crossover open trial , and the main outcome measurements were plasma ionized calcium levels , plasma phosphate levels , plasma intact parathyroid hormone ( PTH ) levels , requirements for supplemental aluminum-aminoacetate therapy , patient tolerance , and cost of therapy . Nineteen patients on chronic hemodialysis were treated with a dialysate calcium concentration of 1.25 mmol/L and a fixed alfacalcidol dose for at least 2 months . All had previously tolerated therapy with calcium carbonate . Of the 19 patients included , 10 completed both treatment arms . After 12 weeks of therapy , the mean ( + /-SEM ) plasma ionized calcium level was significantly lower in the ketoglutarate arm compared with the calcium carbonate arm ( 4.8+/-0.1 mg/dL v 5.2+/-0.1 mg/dL ; P = 0.004 ) , whereas the mean plasma phosphate ( 4.5+/-0.3 mg/dL v 5.1+/-0.1 mg/dL ) and PTH levels ( 266+/-125 pg/mL v 301+/-148 pg/mL ) did not differ significantly between the two treatment arms . Supplemental aluminum-aminoacetate was not required during calcium ketoglutarate treatment , while two patients needed this supplement when treated with calcium carbonate . Five of 17 ( 29 % ) patients were withdrawn from calcium ketoglutarate therapy within 1 to 2 weeks due to intolerance ( anorexia , vomiting , diarrhea , general uneasiness ) , whereas the remaining 12 patients did not experience any side effects at all . The five patients with calcium ketoglutarate intolerance all had pre-existing gastrointestinal symptoms ; four of them had received treatment with cimetidine or omeprazol before inclusion into the study . Calculations based on median doses after 12 weeks showed that the cost of the therapy in Denmark was 10 times higher for calcium ketoglutarate compared with calcium carbonate ( US$ 6.00/d v US$ 0.65/d ) . Calcium ketoglutarate may be an effective and safe alternative to treatment with aluminum-containing phosphate binders in patients on hemodialysis who are intolerant of calcium carbonate or acetate because of hypercalcemia . However , care must be exercised when dealing with patients with pre-existing gastrointestinal discomfort . Due to the high cost of the therapy , calcium ketoglutarate should be used only for selected patients Background —Aortic pulse wave velocity ( PWV ) is a predictor of mortality in patients with end-stage renal failure ( ESRF ) . The PWV is partly dependent on blood pressure ( BP ) , and a decrease in BP can attenuate the stiffness . Whether the changes in PWV in response to decreases in BP can predict mortality in ESRF patients has never been investigated . Methods and Results —One hundred fifty ESRF patients ( aged 52±16 years ) were monitored for 51±38 months . From entry until the end of follow-up , the changes of PWV in response to decreased BP were measured ultrasonographically . BP was controlled by adjustment of “ dry weight ” and , when necessary , with ACE inhibitors , calcium antagonists , and /or & bgr;-blockers , in combination if necessary . Fifty-nine deaths occurred , including 40 cardiovascular and 19 noncardiovascular events . Cox analyses demonstrated that independent of BP changes , the predictors of all-cause and cardiovascular mortality were as follows : absence of PWV decrease in response to BP decrease , increased left ventricular mass , age , and preexisting cardiovascular disease . Survival was positively associated with ACE inhibitor use . After adjustment for all confounding factors , the risk ratio for the absence of PWV decrease was 2.59 ( 95 % CI 1.51 to 4.43 ) for all-cause mortality and 2.35 ( 95 % CI 1.23 to 4.41 ) for cardiovascular mortality . The risk ratio for ACE inhibitor use was 0.19 ( 95 % CI 0.14 to 0.43 ) for all-cause mortality and 0.18 ( 95 % CI 0.06 to 0.55 ) for cardiovascular mortality . Conclusions —These results indicate that in ESRF patients , the insensitivity of PWV to decreased BP is an independent predictor of mortality and that use of ACE inhibitors has a favorable effect on survival that is independent of BP changes We conducted a r and omized unblinded parallel clinical trial to compare the effectiveness , side effects and tolerance between calcium acetate ( CA ) and calcium carbonate ( CC ) in 80 stable chronic hemodialysis patients selected on the basis of their acceptable control of serum phosphorus ( P ) levels with aluminum hydroxide ( AH ) . All patients were dialyzed against the same calcium dialyzate ( 1.62 mmol/l ) . The serum analytical tests included : calcium corrected to total protein , P , PTH ( intact molecule ) and bicarbonate . The study was divided into the following periods : P0 : baseline measurements ; P1 : washout ( withdrawal of AH for 15 days ) ; P2 : r and om allocation to CA and CC treatment at doses equivalent to 75 mEq of elemental calcium , stratified according to previous doses of AH ( 2 months ) ; P3 : adjustment of doses until control P ( 2 months ) . CA was poorly tolerated in 7 patients and CC in 2 ( NS ) . The changes in serum P levels between P0 and P2 periods were lower in the CA group ( 1.73 + /- 0.25 vs. 1.80 + /- 0.50 mmol/l ; p = 0.26 ) than in the CC group ( 1.77 + /- 0.35 vs. 1.93 + /- 0.48 mmol/l ; p = 0.03 , paired t test ) . Serum calcium was hardly modified by CA ( 2.42 + /- 0.20 vs. 2.47 + /- 0.17 mmol/l ; NS ) while in the CC group , it rose significantly ( 2.40 + /- 0.12 vs. 2.55 + /- 0.22 mmol/l ; p = 0.0004 ) . There were no differences in the control of PTH or bicarbonate . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Calcium-based phosphate binders may induce tissue calcification , and little is known about their effects on bone density . We compared the effects of a calcium with a non-calcium phosphate binder on both arterial calcification and bone density measured by computed tomography . METHODS Seventy-two adult haemodialysis patients were r and omized to treatment with calcium carbonate ( CC ) or sevelamer ( SEV ) for 2 years . Electron beam CT scans were performed at baseline and at 6 , 12 and 24 months . Serum phosphorus , calcium , calcium x phosphorus product and intact parathyroid hormone ( iPTH ) were measured and other routine laboratory tests were also carried out . RESULTS The average calcium x phosphorus product was similar in the two treatment groups . However , patients receiving CC had significantly lower average iPTH ( P<0.01 ) , were more likely to have hypercalcaemic episodes ( P = 0.03 ) and had significantly greater increases in coronary artery ( CC median 484 , P<0.0001 , SEV median 37 , P = 0.3118 , between-group P = 0.0178 ) and aortic ( CC median 610 , P = 0.0003 , SEV median 0 , P = 0.5966 , between-group P = 0.0039 ) calcification scores . The CC group also had a significant decrease in trabecular bone density ( CC median -6 % , P = 0.0049 , SEV median + 3 % , P = 0.0296 , between-group P = 0.0025 ) . However , there was no significant difference in cortical bone density between the two groups . CONCLUSIONS This 2 year study shows that calcium carbonate use is continuously associated with progressive arterial calcification in haemodialysis patients . In addition , it suggests that it is also associated with decreased trabecular bone density . However , this latter finding requires confirmation by a study specifically devoted to this issue AIMS High serum phosphorus levels are a common problem in patients receiving long-term dialysis treatment . Lanthanum carbonate ( Fosrenol ) is a new non-aluminum , non-calcium phosphate binder developed for the treatment of hyperphosphatemia in patients with end-stage renal disease ( ESRD ) . We report data from a recent trial , which , for the first time , assessed the efficacy and tolerability of lanthanum carbonate treatment , compared with placebo , in Chinese patients with ESRD . PATIENTS AND METHODS Following a one- to three-week washout phase and a four-week , open-label lanthanum carbonate dose-titration phase , male and female hemodialysis patients were r and omized ( 1:1 ) to receive either lanthanum carbonate or placebo for four weeks . The primary efficacy parameter of the study was the control of serum phosphorus levels ( < or = 1.8 mmol/l [ < or = 5.6 mg/dl ] ) . Secondary endpoints included the profile of serum phosphorus during titration and parathyroid hormone , calcium , and calcium x phosphorus ( Ca x P ) product levels . The safety and tolerability of lanthanum carbonate were assessed by monitoring adverse events throughout the study . RESULTS Mean serum phosphorus level at the end of washout was 2.5 + /- 0.5 mmol/l ( 7.7 + /- 1.5 mg/dl ; n=73 ) , and there was no evidence of a difference in levels between the treatment groups pre-r and omization . At the end of the study , lanthanum carbonate-treated patients had significantly lower phosphorus levels ( 1.6 + /- 0.5 mmol/l [ 5.1 + /- 1.5 mg/dl ] ; n=30 ) than those receiving placebo ( 2.3 + /- 0.4 mmol/l [ 7.2 + /- 1.3 mg/dl ] ; n=31 ; p < 0.001 ) . In addition , a significantly higher proportion of patients receiving lanthanum carbonate had controlled serum phosphorus levels ( 60 % ) compared with the placebo group ( 10 % ; p < 0.001 ) . Ca x P product levels were also significantly lower in the lanthanum carbonate group at the end of r and omized treatment ( p < 0.001 ) . Lanthanum carbonate was well tolerated ; only one serious adverse event was reported , which was unrelated to treatment . CONCLUSIONS Lanthanum carbonate was shown to be an effective and well-tolerated phosphate binder for the treatment of hyperphosphatemia in Chinese patients with ESRD . This finding supports the results of previous US and European studies , which have also shown that lanthanum carbonate treatment effectively controls serum phosphorus levels BACKGROUND Sevelamer hydrochloride is a recently approved calcium- and aluminium-free phosphate binder . A r and omized study comparing sevelamer and calcium acetate was performed to assess the control of hyperphosphatemia in hemodialysis patients . METHODS Administration of phosphate binders was discontinued during a two-week washout period . The patients were then r and omized to receive sevelamer or calcium acetate . The laboratory tests were performed monthly for 34 weeks . RESULTS There was a statistically significant decrease of serum phosphorus in both sevelamer and calcium acetate treatments . In addition , sevelamer improved the lipid profile . CONCLUSION This study confirms that sevelamer is effective at lowering serum phosphorus in hemodialysis patients and that it has several striking properties that could be beneficial in atherosclerosis in dialysis patients Since dietary restrictions and phosphorus removal by haemodialysis ( HD ) are not sufficient to control serum phosphate ( s-phosphate ) levels in dialysis patients the use of oral phosphate binders is m and atory . Calcium ketoglutarate ( CaKE ) is an analogue of glutamic acid exerting phosphate binding properties . Therefore we compared this substance to calcium acetate ( CaAC ) in a 24-weeks open cross-over trial in 28 maintenance HD patients . Medications and HD prescriptions were kept unchanged during the trial . Following 2 weeks of withdrawal of phosphate binders , patients were r and omly assigned to one of the calcium salts for 12 weeks ; after a second withdrawal of 2 weeks , all patients were shifted to the other treatment for another 12 weeks . All patients received equimolar doses of CaKE and CaAC with respect to the amount of prescribed elemental calcium . Treatment with CaAC and CaKE significantly reduced s-phosphate levels after 4 weeks ( CaAC 1.95+/-0.6 vs. 2. Output:	Compared with calcium-based agents , lanthanum significantly decreased end-of-treatment serum calcium and calcium-phosphorus product levels , but with similar end-of-treatment phosphorus levels . Effects of calcium acetate on biochemical end points were similar to those of calcium carbonate . Existing data are insufficient to conclude for a differential impact of any phosphate binder on cardiovascular mortality or other patient-level outcome . Currently , there are insufficient data to establish the comparative superiority of non-calcium-binding agents over calcium-containing phosphate binders for such important patient-level outcomes as all-cause mortality and cardiovascular end points .
MS2929	*TASK* the task is to summarize an input biomedical literature in six sentences *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 effectiveness of specific systems changes to reduce DTN ( door-to-needle ) time has not been fully evaluated . We analyzed the impact of 4 specific DTN time reduction strategies implemented prospect ively in a staggered fashion . Methods and Results — The HASTE ( Hurry Acute Stroke Treatment and Evaluation ) project was implemented in 3 phases at a single academic medical center . In HASTE I ( June 6 , 2012 to June 5 , 2013 ) , baseline performance was analyzed . In HASTE II ( June 6 , 2013 to January 24 , 2015 ) , 3 changes were implemented : ( 1 ) a STAT stroke protocol to prenotify the stroke team about incoming stroke patients ; ( 2 ) administering alteplase at the computed tomography ( CT ) scanner ; and ( 3 ) registering the patient as unknown to allow immediate order entry . In HASTE III ( January 25 , 2015 to June 29 , 2015 ) , we implemented a process to bring the patient directly to CT on the emergency medical services stretcher . Log-transformed DTN time was modeled . Data from 350 consecutive alteplase-treated patients were analyzed . Multivariable regression showed the following factors to be significant : giving alteplase in the CT ( 32 % decrease in DTN time , 95 % confidence interval [ CI ] 38%–55 % ) , stretcher to CT ( 30 % decrease in DTN time , 95 % CI 16%–42 % ) , patient registered as unknown ( 12 % decrease in DTN time , 95 % CI 3%–20 % ) , STAT stroke protocol ( 11 % decrease in DTN time , 95 % CI 1%–20 % ) , and stroke severity ( National Institutes of Health Stroke Scale score 6–8 : 19 % decrease in DTN time , 95 % CI 6%–31 % ; National Institutes of Health Stroke Scale score > 8 : 27 % decrease in DTN time , 95 % CI 17%–37 % ) . Conclusions — Taking the patient to CT on the emergency medical services stretcher , registering the patient as unknown , STAT stroke protocol , and administering alteplase in CT are associated with lower DTN time Background and Purpose Use of thrombolysis and acute treatments for cerebral infa rct ion may require that acute stroke be treated as a medical emergency . To assess the factors influencing the time to admission in acute stroke , we conducted a prospect i ve study of all such patients admitted to the hospitals in Leicester , UK , over a 12-month period . Methods Factors assessed were age , sex , time of stroke onset , stroke severity , home circumstances , and routes of admission . Initial between-group comparisons were made with the Mann-Whitney U test . The individual contribution of each of these variables was assessed with multiple linear regression analysis . Results An accurate time of stroke onset was identified in 374 ( 70 % ) of 535 registered patients ( median age 77 [ range , 29–98 ] years ; 332 men , 203 women ) . Median time from onset to admission was 6 hours , with 25 % of the patients arriving in less than 2.5 hours and 75 % in less than 11.5 hours . Multiple regression confirmed that only admission through the bed allocation bureau ( p<0.001 ) , living alone ( p<0.001 ) , and nocturnal onset ( p=0.003 ) prolonged delay time . Despite patients over 70 years of age taking a median of 7 hours from onset to admission compared with 4 hours for those under age 70 ( p<0.001 ) , the effect of age appeared to be dependent on these three factors . Age , sex , level of consciousness , rural domicile , and place of admission did not influence the delay time independently . Conclusions We have identified some of the factors affecting the hospital admission delay time for stroke . With the possible advent of effective early treatments for stroke , these factors will need to be addressed Background and Purpose — Faster treatment with intravenous tissue-type plasminogen activator ( tPA ) is likely to improve outcomes . Optimizing prehospital triage by mobile stroke units ( MSUs ) may speed treatment times . The Benefits of Stroke Treatment Delivered Using a Mobile Stroke Unit ( BEST-MSU ) study was launched in May 2014 using the first MSU in the United States to compare stroke management using an MSU versus st and ard management ( SM ) . Herein , we describe the results of the prespecified , nonr and omized run-in phase design ed to obtain preliminary data on study logistics . Methods — The run-in phase consisted of 8 MSU weeks when all-patient care occurred on the MSU and 2 SM weeks when the MSU nurse met personnel on scene or at the emergency department to ensure comparability with MSU patients . Telemedicine was independently performed in 9 MSU cases . Results — Of 130 alerts , 24 MSU and 2 SM patients were enrolled . Twelve of 24 MSU patients received tPA on board ; 4 were treated within 60 minutes of last seen normal , and 4 went on to endovascular treatment . There were no hemorrhagic complications . Four had primary intracerebral hemorrhage . Agreement on tPA eligibility between the onsite and telemedicine physician was 90 % . Conclusions — The run-in phase provided a tPA treatment rate of 1.5 patients per week , assured us that treatment within 60 minutes of onset is possible , and enabled enrollment of patients on SM weeks . We also recognized the opportunity to assess the effect of the MSU on endovascular treatment and intracerebral hemorrhage . Challenges include the need to control biased patient selection on MSU versus SM weeks and establish inter-rater agreement for tPA treatment using telemedicine Background and Purpose — Enrollment in acute stroke trials at a stroke center with multiple study protocol s may delay the initiation of intravenous thrombolytics in patients who present within 3 hours of symptom onset . Methods — We studied all patients presenting with acute ischemic stroke over the past 3.5 years who qualified for thrombolysis within 3 hours of symptom onset . We collected demographics , baseline National Institutes of Health Stroke Scale scores , CT findings , and arrival-to-treatment times and compared patients treated with intravenous thrombolytics in a clinical trial with patients who received st and ard of care intravenous tissue plasminogen activator . Results — Of 290 treated patients , 19 were enrolled in prelytic studies , 46 were enrolled in postlytic studies , and 225 were treated with st and ard intravenous tissue plasminogen activator . There was no significant difference in age , gender , National Institutes of Health Stroke Scale score , admission glucose , or changes on CT . There was no difference in onset-to-arrival time or arrival-to-treatment time between patients enrolled in clinical studies and those who received st and ard treatment . However , among study patients , prelytic r and omization led to a significantly longer arrival-to-treatment time by 13 minutes ( P=0.028 ) . Conclusion — We found that trials requiring prethrombolytic r and omization can lead to a delay in the initiation of treatment . Future studies are needed to determine if such a delay is clinical ly significant and can be shortened by improved enrollment strategies Background and Purpose — Thrombolysis for treatment of acute ischemic stroke should be administered as fast as possible after symptom onset . The aim of this study was to examine , in our tertiary care center , the time intervals preceding intra-arterial thrombolysis in order to accelerate and optimize the management of acute strokes . Methods — Between January 1 , 2000 , and April 30 , 2002 , 597 patients with acute stroke were admitted to our stroke center . One hundred forty-eight patients underwent diagnostic arteriography , and 100 ( 16.8 % ) received intra-arterial thrombolysis . For all patients , we prospect ively recorded and analyzed the time of symptom onset , admission , CT and /or MRI scan , diagnostic arteriography , and , if performed , intra-arterial thrombolysis . Results — The mean time to arrival in the emergency department was 99 minutes for patients who were admitted directly ( Bern patients ) , 127 minutes for those who were referred from community hospitals without a CT scanner ( non-Bern/−CT patients ) , and 210 minutes for patients from hospitals with imaging facilities ( non-Bern/+CT patients ) . The mean delay from symptom onset to treatment was 234 minutes for Bern patients , 269 minutes for non-Bern/−CT patients , and 302 minutes for non-Bern/+CT patients . The patients from the last group needed longer to receive intra-arterial thrombolysis than did patients who were admitted directly ( P = 0.002 ) or who were transferred from a hospital without a CT scanner ( P = 0.03 ) . Conclusions — This prospect i ve study indicates that direct referral without prior imaging at community hospitals shortens the time until intra-arterial thrombolysis . In addition , our in-hospital delay preceding intra-arterial thrombolysis is longer than the delays reported for intravenous thrombolysis and indicates potential for improvement Background Intravenous thrombolysis ( IVT ) with ( recombinant ) tissue plasminogen activator is an effective treatment in acute ischemic stroke . However , IVT is contraindicated when blood pressure is above 185/110 mmHg , because of an increased risk on symptomatic intracranial hemorrhage . In current Dutch clinical practice , two distinct strategies are used in this situation . The active strategy comprises lowering blood pressure with antihypertensive agents below these thresholds to allow start of IVT . In the conservative strategy , IVT is administered only when blood pressure drops spontaneously below protocol led thresholds . A retrospective analysis in two recent stroke trials showed a non-significant signal towards better functional outcome in the active group ; robust evidence for either strategy , however , is lacking . We hypothesize that ( I ) the active strategy leads to a better functional outcome three months after acute ischemic stroke . Secondary hypotheses are that this effect occurs despite ( II ) increasing the number of symptomatic intracranial hemorrhages , and could be attributable to ( III ) a higher rate of IVT treatments and ( IV ) a shorter door-to-needle time . Methods and design The TRUTH is a prospect i ve , observational , cluster-based , parallel group follow-up study ; in which participating centers continue their current local treatment guidelines . Outcomes of patients admitted to centers with an active will be compared to those admitted to centers with a conservative strategy . The primary outcome is functional outcome on the modified Rankin Scale at three months . Secondary outcomes are symptomatic intracranial hemorrhage , IVT treatment and door-to-needle time . We based our sample size estimate on an ordinal analysis of the mRS with the “ proportional odds ” model . With the aforementioned signal observed in a recent retrospective study in these patients as an estimate of the effect size and with alpha 0 · 05 , this analysis would have an 80 % power with a total number of 600 patients . Corrections for expected imbalance in group size and clustering effects result ed in a sample size of 1235 patients . Discussion The TRUTH is the first large prospect i ve study specifically study ing IVT-c and i date s with elevated blood pressure , and has the potential to change clinical practice and optimize acute stroke care in these patients BACKGROUND The time from symptom onset to seeking medical assistance ( decision delay ) accounts for a proportion of prehospital delay in acute stroke . The aims of this study were to identify factors related to decision delay and calling the emergency medical services ( EMS ) as the first medical contact . METHODS Data were prospect ively collected from 350 patients with acute stroke or transient ischemic attack . Data on decision delay , prehospital delay , types of first medical contact , and previous stroke knowledge were recorded . Multivariable logistic regression analyses were conducted to identify factors related to decision delay of 1 hour or less and calling the EMS as the first medical contact . RESULTS The median decision delay was 2.0 hours . Decision delay accounted for 62.3 % of prehospital delay ( median value ) . Moderate ( National Institutes of Health Stroke Scale [ NIHSS ] score 8 - 16 ; odds ratio [ OR ] 4.16 [ 95 % confidence interval 1.86 - 9.30 ] ) or severe symptoms ( NIHSS score ≥ 17 ; OR 10.38 [ 2.70 - 39.90 ] ) and living together ( OR 1.84 [ 1.02 - 3.43 ] ) were associated with decision delay of 1 hour or less . Moderate ( OR 6.31 [ 2.79 - 14.29 ] ) or severe symptoms ( OR 8.44 [ 2.64 - 26.98 ] ) were associated with calling the EMS as the first medical contact . Previous stroke knowledge did not affect an early decision or EMS use . CONCLUSIONS The decision to seek medical assistance in acute stroke accounts for more than half of the prehospital delay . Severity of symptoms and living together are related to an early decision ( ≤1 hour ) . Previous stroke knowledge does not affect decision delay or EMS use Rationale Mobile stroke units speed treatment for acute ischemic stroke , thereby possibly improving outcomes . Aim To compare mobile stroke unit and st and ard management clinical outcomes , healthcare utilization , and cost-effectiveness in tissue plasminogen activator-eligible acute ischemic stroke patients calling 911 . Sample size 693 . Eighty percent power with 0.05 type I error rate to detect a difference of 0.09 in mean utility-weighted modified Rankin scale between groups . Output:	In-hospital factors relating to assessment , imaging and thrombolysis administration also contributed .
MS2930	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: There are no data on the prevalence and other epidemiologic characteristics of chronic symmetric polyneuropathy ( CSP ) in the community . This study was design ed to assess the prevalence and risk factors of CSP in well-defined elderly ( 55 years and older ) population s from two separate areas in Italy . Thirty-five general practitioners working in the two areas were invited to interview a r and om sample of patients requesting consultation . They used a pretested question naire which focused on selected symptoms of polyneuropathy , common risk factors for CSP , and current drug treatments . Patients giving affirmative answers to the questions on screening symptoms received a further clinical evaluation by a neurologist . Details are given of the general characteristics of the study areas and population s , the methods of case ascertainment , the validation of the screening instruments , and the results of a pilot study Objective This project evaluated the utility of quantitative sensory techniques in predicting the development of neuropathy for subjects participating in a prospect i ve study . Research Design and Methods Distal symmetric polyneuropathy was evaluated in 77 insulin-dependent diabetes mellitus individuals via quantitative sensory testing , nerve conduction studies , and clinical examination . Results Although the specificity and positive predictive value were low for the quantitative sensory techniques as predictors of neuropathy diagnosed on clinical exam ∼2 yr later , the sensitivity for vibratory thresholds was high ( 100 % ) . Variability over the 2-yr interval was shown on follow-up testing for each of the objective assessment modalities and it was not explained by differences for potential risk factors measured at baseline . Conclusion Despite a cross-sectional relationship between the assessment modalities and clinical ly overt neuropathy at baseline , these follow-up data suggest that the potential for the objective modalities as predictors of clinical ly diagnosed neuropathy may be limited Article abstract -Despite prominent symptoms of neuropathic pain , patients with small-fiber sensory neuropathies have few objective abnormalities on clinical examination and routine electrodiagnostic studies . We quantified intraepidermal nerve fiber ( IENF ) density in sections of skin obtained by punch skin biopsy , and found it to be significantly reduced in patients with painful sensory neuropathies compared with age-matched control subjects . In addition , IENF density correlated with clinical estimates of neuropathy severity , as judged by the extent of clinical ly identifiable sensory abnormalities . IENF density at the calf was lower than that obtained from skin at more proximal sites , indicating the length dependency of small-fiber loss in these neuropathies . NEUROLOGY 1997;48 : 708 - We assessed the involvement of somatic unmyelinated fibers in sensory ganglionopathies by skin biopsy and quantitative sensory testing ( QST ) . Sixteen patients with ganglionopathy , 16 with axonal neuropathy , and 15 normal controls underwent skin biopsy at the proximal thigh and the distal leg . Intraepidermal nerve fibers ( IENF ) were immunostained by antiprotein gene product 9.5 , and their linear density was quantified under light microscopy . Confocal microscopy studies with double staining of nerve fibers and basement membrane were also performed . Healthy subjects and neuropathy patients showed the typical proximodistal gradient of IENF density ; in neuropathies , values were significantly lower at the distal site of the leg , confirming the length-dependent loss of cutaneous innervation . Conversely , ganglionopathy patients with hyperalgesic symptoms did not show any change of IENF density between the proximal thigh and the distal leg . The distinct pattern of epidermal denervation seen in sensory ganglionopathy reflected the degeneration of somatic unmyelinated fibers in a fashion that was not length-dependent , which was consistent with both clinical and neurophysiologic observations and supported the diagnosis Output:	The literature indicates that symptoms alone have relatively poor diagnostic accuracy in predicting the presence of polyneuropathy ; signs are better predictors of polyneuropathy than symptoms ; and single abnormalities on examination are less sensitive than multiple abnormalities in predicting the presence of polyneuropathy . The combination of neuropathic symptoms , signs , and electrodiagnostic findings provides the most accurate diagnosis of distal symmetric polyneuropathy . The highest likelihood of polyneuropathy ( useful for clinical trials ) occurs with a combination of multiple symptoms , multiple signs , and abnormal electrodiagnostic studies . A modest likelihood of polyneuropathy ( useful for field or epidemiologic studies ) occurs with a combination of multiple symptoms and multiple signs when the results of electrodiagnostic studies are not available . A lower likelihood of polyneuropathy occurs when electrodiagnostic studies and signs are discordant .
MS2931	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: PURPOSE To investigate the effect of ice slurry ingestion on thermoregulatory responses and submaximal running time in the heat . METHODS On two separate occasions , in a counterbalanced order , 10 males ingested 7.5 g·kg(-1 ) of either ice slurry ( -1 ° C ) or cold water ( 4 ° C ) before running to exhaustion at their first ventilatory threshold in a hot environment ( 34.0 ° C ± 0.2 ° C , 54.9 % ± 5.9 % relative humidity ) . Rectal and skin temperatures , HR , sweating rate , and ratings of thermal sensation and perceived exertion were measured . RESULTS Running time was longer ( P = 0.001 ) after ice slurry ( 50.2 ± 8.5 min ) versus cold water ( 40.7 ± 7.2 min ) ingestion . Before running , rectal temperature dropped 0.66 ° C ± 0.14 ° C after ice slurry ingestion compared with 0.25 ° C ± 0.09 ° C ( P = 0.001 ) with cold water and remained lower for the first 30 min of exercise . At exhaustion , however , rectal temperature was higher ( P = 0.001 ) with ice slurry ( 39.36 ° C ± 0.41 ° C ) versus cold water ingestion ( 39.05 ° C ± 0.37 ° C ) . During exercise , mean skin temperature was similar between conditions ( P = 0.992 ) , as was HR ( P = 0.122 ) and sweat rate ( P = 0.242 ) . After ice slurry ingestion , subjects stored more heat during exercise ( 100.10 ± 25.00 vs 78.93 ± 20.52 W·m(-2 ) , P = 0.005 ) , and mean ratings of thermal sensation ( P = 0.001 ) and perceived exertion ( P = 0.022 ) were lower . CONCLUSIONS Compared with cold water , ice slurry ingestion lowered preexercise rectal temperature , increased submaximal endurance running time in the heat ( + 19 % ± 6 % ) , and allowed rectal temperature to become higher at exhaustion . As such , ice slurry ingestion may be an effective and practical precooling maneuver for athletes competing in hot environments PURPOSE To develop and investigate the efficacy of a new precooling strategy combining external and internal techniques on the performance of a cycling time trial ( TT ) in a hot and humid environment . METHODS Eleven well-trained male cyclists undertook three trials of a laboratory-based cycling TT simulating the course characteristics of the Beijing Olympic Games event in a controlled hot and humid environment ( 32 ° C-35 ° C at 50%-60 % relative humidity ) . The trials , separated by 3 - 7 d , were undertaken in a r and omized crossover design and consisted of the following : 1 ) CON-no treatment apart from the ad libitum consumption of cold water ( 4 ° C ) , 2 ) STD COOL-whole-body immersion in cold ( 10 ° C ) water for 10 min followed by wearing a cooling jacket , or 3 ) NEW COOL-combination of consumption of 14 g of ice slurry ( " slushie " ) per kilogram body mass made from a commercial sports drink while applying iced towels . RESULTS There was an observable effect on rectal temperature ( T(rec ) ) before the commencement of the TT after both precooling techniques ( STD COOL < NEW COOL < CON , P < 0.05 ) , but pacing of the TT result ed in similar T(rec ) , HR , and RPE throughout the cycling protocol in all trials . NEW COOL was associated with a 3.0 % increase in power ( approximately 8 W ) and a 1.3 % improvement in performance time ( approximately 1:06 min ) compared with the CON trial , with the true likely effects ranging from a trivial to a large benefit . The effect of the STD COOL trial compared with the CON trial was " unclear . " CONCLUSIONS This new precooling strategy represents a practical and effective technique that could be used by athletes in preparation for endurance events undertaken in hot and humid conditions PURPOSE To determine the effect of thermal state and thermal comfort on cycling performance in the heat . METHODS Seven well-trained male triathletes completed 3 performance trials consisting of 60 min cycling at a fixed rating of perceived exertion ( 14 ) followed immediately by a 20-km time trial in hot ( 30 ° C ) and humid ( 80 % relative humidity ) conditions . In a r and omized order , cyclists either drank ambient-temperature ( 30 ° C ) fluid ad libitum during exercise ( CON ) , drank ice slurry ( -1 ° C ) ad libitum during exercise ( ICE ) , or precooled with iced towels and ice slurry ingestion ( 15 g/kg ) before drinking ice slurry ad libitum during exercise ( PC+ICE ) . Power output , rectal temperature , and ratings of thermal comfort were measured . RESULTS Overall mean power output was possibly higher in ICE ( + 1.4%±1.8 % [ 90 % confidence limit ] ; 0.4 > smallest worthwhile change [ SWC ] ) and likely higher PC+ICE ( + 2.5%±1.9 % ; 1.5>SWC ) than in CON ; however , no substantial differences were shown between PC+ICE and ICE ( unclear ) . Time-trial performance was likely enhanced in ICE compared with CON ( + 2.4%±2.7 % ; 1.4>SWC ) and PC+ICE ( + 2.9%±3.2 % ; 1.9>SWC ) . Differences in mean rectal temperature during exercise were unclear between trials . Ratings of thermal comfort were likely and very likely lower during exercise in ICE and PC+ICE , respectively , than in CON . CONCLUSIONS While PC+ICE had a stronger effect on mean power output compared with CON than ICE did , the ICE strategy enhanced late-stage time-trial performance the most . Findings suggest that thermal comfort may be as important as thermal state for maximizing performance in the heat We used incorrect visual feedback of ambient and core temperature in the heat to test the hypothesis that deception would alleviate the decrement in cycling performance compared to a no deception trial . Seven males completed three 30 min cycling time trials in a r and omised order on a Kingcycle ergometer . One time trial was in temperate , control conditions ( CON : 21.8 ± 0.6 ° C ; 43.3 ± 4.3%rh ) , the others in hot , humid conditions ( HOT : 31.4 ± 0.3 ° C ; 63.9 ± 4.5%rh ) . In one of the hot , humid conditions ( 31.6 ± 0.5 ° C ; 65.4 ± 4.3%rh ) , participants were deceived ( DEC ) into thinking the ambient conditions were 26.0 ° C ; 60.0%rh and their core temperature was 0.3 ° C lower than it really was . Compared to CON ( 16.63 ± 2.43 km ) distance covered was lower in HOT ( 15.88 ± 2.75 km ; P < 0.05 ) , but DEC ameliorated this ( 16.74 ± 2.87 km ; P < 0.05 ) . Mean power output was greater in DEC ( 184.4 ± 60.4 W ) than HOT ( 168.1 ± 54.1 W ; P < 0.05 ) and no difference was observed between CON and DEC . Rectal temperature and iEMG of the vastus lateralis were not different , but RPE in the third minute was lower in DEC than HOT ( P < 0.05 ) . Deception improved performance in the heat by creating a lower RPE , evidence of a subtle mismatch between the subconscious expectation and conscious perception of the task dem and QUESTIONS Does the PEDro scale measure only one construct ie , the method ological quality of clinical trials ? What is the hierarchy of items of the PEDro scale from least to most adhered to ? Is there any effect of year of publication of trials on item adherence ? Are PEDro scale ordinal scores equivalent to interval data ? DESIGN Rasch analysis of two independent sample s of 100 clinical trials from the PEDro data base scored using the PEDro scale . RESULTS Both sample s of PEDro data showed fit to the Rasch model with no item misfit . The PEDro scale item hierarchy was the same in both sample s , ranging from the most adhered to item r and om allocation , to the least adhered to item therapist blinding . There was no differential item functioning by year of publication . Original PEDro ordinal scores were highly correlated with transformed PEDro interval scores ( r = 0.99 ) . CONCLUSION The PEDro scale is a valid measure of the method ological quality of clinical trials . It is valid to sum PEDro scale item scores to obtain a total score that can be treated as interval level measurement and subjected to parametric statistical analysis ABSTRACT This investigation compared the effects of external pre-cooling and mid-exercise cooling methods on running time trial performance and associated physiological responses . Nine trained male runners completed familiarisation and three r and omised 5 km running time trials on a non-motorised treadmill in the heat ( 33 ° C ) . The trials included pre-cooling by cold-water immersion ( CWI ) , mid-exercise cooling by intermittent facial water spray ( SPRAY ) , and a control of no cooling ( CON ) . Temperature , cardiorespiratory , muscular activation , and perceptual responses were measured as well as blood concentrations of lactate and prolactin . Performance time was significantly faster with CWI ( 24.5 ± 2.8 min ; P = 0.01 ) and SPRAY ( 24.6 ± 3.3 min ; P = 0.01 ) compared to CON ( 25.2 ± 3.2 min ) . Both cooling strategies significantly ( P < 0.05 ) reduced forehead temperatures and thermal sensation , and increased muscle activation . Only pre-cooling significantly lowered rectal temperature both pre-exercise ( by 0.5 ± 0.3 ° C ; P < 0.01 ) and throughout exercise , and reduced sweat rate ( P < 0.05 ) . Both cooling strategies improved performance by a similar magnitude , and are ergogenic for athletes . The observed physiological changes suggest some involvement of central and psychophysiological mechanisms of performance improvement Abstract Although pre-cooling is known to enhance exercise performance , the optimal cooling intensity is unknown . We hypothesized that mild cooling opposed to strong cooling circumvents skin vasoconstriction and thermogenesis , and thus improves cooling efficiency reflected in improved time to exhaustion . Eight males undertook three r and omized trials , consisting of a pre-cooling and an exercise session . During the pre-cooling , performed in a room of 24.6 ± 0.4 ° C and 24 ± 6 % relative humidity , participants received either 45 min of mild cooling using an evaporative cooling shirt or strong cooling using an ice-vest . A no-cooling condition was added as a control . Subsequent cycling exercise was performed at 65%[Vdot]O2peak in a climatic chamber of 29.3 ± 0.2 ° C and 80 ± 3 % relative humidity . During the pre-cooling session , mild and strong cooling decreased the skin blood flow compared with the control . However , no differences were observed between mild and strong cooling . No thermogenesis was observed in any conditions investigated . The reduction of body heat content after pre-cooling was two times larger with strong cooling ( 39.5 ± 8.4 W · m−2 ) than mild cooling ( 21.2 ± 5.1 W · m−2 ) . This result ed in the greatest improvement in time to exhaustion with strong cooling . We conclude that the cooling intensities investigated had a similar effect on cooling efficiency ( vasoconstriction and thermogenesis ) and that the improved performance after strong cooling is attributable to the greater decrease in body heat content Abstract This study investigated the effect of ice slurry ingestion during a triathlon on intragastric temperature and 10 km running performance in the heat . Nine well-trained male triathletes performed two r and omised trials of a simulated Olympic distance triathlon in hot conditions ( 32–34 ° C ) . Exercise intensity during the swim ( 1500 m ) and cycle ( 1 hr ) legs was st and ardised , and the 10 km run leg was a self-paced time trial . During the cycle leg , either 10 g · kgBM−1 of ice slurry ( < 1 ° C ) or room temperature fluid ( 32–34 ° C ) was ingested . In the run leg of the ice slurry trial , performance time ( 43.4 ± 3.7 vs. 44.6 ± 4.0 min ; P = 0.03 ) , intragastric temperature ( at 1.5 km ; 35.5 ± 1.2 vs. 37.5 ± 0.4 ° C ; P = 0.002 ) and perceived thermal stress ( at 5 km ; 73 ± 9 vs. 80 ± 7 mm ; P = 0.04 ) were significantly lower . Oxygen consumption was significantly higher in the ice trial between 9.5–10 km ( 52.4 ± 3.4 vs. 47.8 ± 5.4 mL · kg−1 · min−1 ; P = 0.04 ) . The results suggest ice slurry ingestion was an effective ergogenic aid for triathlon running performance in Output:	Current evidence suggests that whilst other strategies ameliorate physiological or perceptual responses throughout endurance exercise in hot conditions , ingesting cooling aids before and during exercise provides a small benefit , which is of practical significance to athletes ' time trial performance
MS2932	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Anemia , a common complication of chronic kidney disease , usually develops as a consequence of erythropoietin deficiency . Recombinant human erythropoietin ( epoetin alfa ) is indicated for the correction of anemia associated with this condition . However , the optimal level of hemoglobin correction is not defined . METHODS In this open-label trial , we studied 1432 patients with chronic kidney disease , 715 of whom were r and omly assigned to receive a dose of epoetin alfa targeted to achieve a hemoglobin level of 13.5 g per deciliter and 717 of whom were assigned to receive a dose targeted to achieve a level of 11.3 g per deciliter . The median study duration was 16 months . The primary end point was a composite of death , myocardial infa rct ion , hospitalization for congestive heart failure ( without renal replacement therapy ) , and stroke . RESULTS A total of 222 composite events occurred : 125 events in the high-hemoglobin group , as compared with 97 events in the low-hemoglobin group ( hazard ratio , 1.34 ; 95 % confidence interval , 1.03 to 1.74 ; P=0.03 ) . There were 65 deaths ( 29.3 % ) , 101 hospitalizations for congestive heart failure ( 45.5 % ) , 25 myocardial infa rct ions ( 11.3 % ) , and 23 strokes ( 10.4 % ) . Seven patients ( 3.2 % ) were hospitalized for congestive heart failure and myocardial infa rct ion combined , and one patient ( 0.5 % ) died after having a stroke . Improvements in the quality of life were similar in the two groups . More patients in the high-hemoglobin group had at least one serious adverse event . CONCLUSIONS The use of a target hemoglobin level of 13.5 g per deciliter ( as compared with 11.3 g per deciliter ) was associated with increased risk and no incremental improvement in the quality of life . ( Clinical Trials.gov number , NCT00211120 [ Clinical Trials.gov ] . ) BACKGROUND Diagnosis of iron deficiency in hemodialysis patients is limited by the inaccuracy of commonly used tests . Reticulocyte hemoglobin content ( CHr ) is a test that has shown promise for improved diagnosis in preliminary studies . The purpose of this study was to compare iron management guided by serum ferritin and transferrin saturation to management guided by CHr . METHODS A total of 157 hemodialysis patients from three centers were r and omized to iron management based on ( group 1 ) serum ferritin and transferrin saturation , or ( group 2 ) CHr . Patients were followed for six months . Treatment with intravenous iron dextran , 100 mg for 10 consecutive treatments was initiated if ( group 1 ) serum ferritin < 100 ng/mL or transferrin saturation < 20 % , or ( group 2 ) CHr < 29 pg . RESULTS There was no significant difference between groups in the final mean hematocrit or epoetin dose . The mean weekly dose of iron dextran was 47.7 + /- 35.5 mg in group 1 compared to 22.9 + /- 20.5 mg in group 2 ( P = 0.02 ) . The final mean serum ferritin was 399.5 + /- 247.6 ng/mL in group 1 compared to 304.7 + /- 290.6 ng/mL in group 2 ( P < 0.05 ) . There was no significant difference in final TSAT or CHr . Coefficient of variation was significantly lower for CHr than serum ferritin and transferrin saturation ( 3.4 % vs. 43.6 % and 39.5 % , respectively ) . CONCLUSIONS CHr is a markedly more stable analyte than serum ferritin or transferrin saturation , and iron management based on CHr results in similar hematocrit and epoetin dosing while significantly reducing IV iron exposure BACKGROUND Iron deficiency is a frequent cause of recombinant human erythropoietin (rhEPO)-resistant anemia in hemodialysis patients . Both reticulocyte hemoglobin content ( CHr ) and transferrin saturation ( TSAT ) have been proposed as markers of iron deficiency , but it is unclear which parameter is superior . METHODS To compare the efficacy of CHr and TSAT as an indicator for treatment of iron deficiency , we conducted a single-center , open-label , prospect i ve , r and omized , controlled trial at the Kidney Center in Shinraku-en Hospital of 197 Japanese patients on chronic hemodialysis . After 4 weeks of run-in period during which iron supplementation was suspended , 100 patients who were r and omized to the CHr group received 240 mg iron colloid intravenously over 2 weeks when CHr less than 32.5 pg , and 97 patients who were r and omized to the TSAT group received the same doses of iron colloid when TSAT less than 20 % . We measured the rhEPO dose needed to maintain pre study hematocrit levels , hematocrit , CHr , TSAT , serum ferritin , percentage of hypochromic red blood cells , and total iron administered . RESULTS Sixteen weeks later , 94 patients in the CHr group and 89 patients in the TSAT group finished the study . The doses of rhEPO required decreased by 35.8 % ( 4081 to 2629 U/week , P < 0.005 ) in the TSAT group , but not significantly in the CHr group ( 4121 to 3606 U/week ) . Although CHr increased promptly after the iron administration in both groups , TSAT increased only in the TSAT group . CONCLUSIONS Although CHr reflects the iron status more sensitively , TSAT is a better clinical marker for iron supplementation therapy Background / Aims : Renal anemia is one of the commonest complications of chronic renal failure . Iron deficiency is the most common factor which affects the efficacy of recombinant human erythropoietin ( EPO ) therapy . Intravenous ( i.v . ) iron preparations are commonly used in Western countries , but iron sucrose is seldom used in Chinese patients on maintenance hemodialysis . The aim of the present study was to explore the safety and efficacy of i.v . iron sucrose in Chinese patients on maintenance hemodialysis and to explore the optimal administration frequency . Methods : One hundred and thirty-six patients on maintenance hemodialysis were involved in this r and omized , controlled , parallel-group , single-center trial . Seventy patients received i.v . iron sucrose ( Venofer ® , delivering 100 mg iron ) twice a week for 8 weeks , then once a week for another 4 weeks . The other 66 patients received oral ( p.o . ) ferrous succinate 200 mg t.i.d . for 12 weeks . Levels of serum ferritin ( SF ) , transferrin saturation ( TSAT ) , hemoglobin ( Hb ) and hematocrit ( Hct ) were assessed at baseline and then again after 4 , 8 and 12 weeks of treatment . Results : There were no differences between i.v . and p.o . groups in terms of sex , age , duration of hemodialysis , dialysis frequency per week , EPO dosage per week , the level of intact parathyroid hormone , serum creatinine , blood urea nitrogen , or hematological parameters at baseline . After 8 and 12 weeks of treatment , mean Hb concentration and Hct were significantly increased in the i.v . group , and were also significantly higher than those in the p.o . group . Levels of SF and TSAT were also significantly increased in the i.v . group , and significantly higher than in the p.o . group . After 8 weeks , the response rate in the i.v . group was 88.6 % , which was significantly higher than that in the p.o . group . The mean EPO dose was significantly lower in the i.v . group than the p.o . group . Hb , Hct , SF and TSAT levels were maintained between 8 and 12 weeks in the i.v . group despite the decrease in dose frequency . There were no adverse events related to i.v . iron administration . Twenty-two patients in the p.o . group had adverse gastrointestinal effects . After 12 weeks , the cost of EPO + i.v . iron was significantly higher than the cost of EPO + p.o . iron . Conclusion : Intravenous iron sucrose can effectively increase serum iron parameters and Hb levels in Chinese patients on maintenance hemodialysis and is well tolerated . Infusion of i.v . iron sucrose 100 mg per week can maintain serum iron parameters and Hb levels in Chinese patients on maintenance hemodialysis and can permit reductions in the required dose of EPO . However , the total cost of i.v . iron is relatively high BACKGROUND AND OBJECTIVES Hepcidin is a key regulator of iron homeostasis , but its study in the setting of chronic kidney disease ( CKD ) has been hampered by the lack of vali date d serum assays . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS This study reports the first measurements of bioactive serum hepcidin using a novel competitive ELISA in 48 pediatric ( PCKD2 - 4 ) and 32 adult ( ACKD2 - 4 ) patients with stages 2 to 4 CKD along with 26 pediatric patients with stage 5 CKD ( PCKD5D ) on peritoneal dialysis . RESULTS When compared with their respective controls ( pediatric median = 25.3 ng/ml , adult = 72.9 ng/ml ) , hepcidin was significantly increased in PCKD2 - 4 ( 127.3 ng/ml ) , ACKD2 - 4 ( 269.9 ng/ml ) , and PCKD5D ( 652.4 ng/ml ) . Multivariate regression analysis was used to assess the relationship between hepcidin and indicators of anemia , iron status , inflammation , and renal function . In PCKD2 - 4 ( R(2 ) = 0.57 ) , only ferritin correlated with hepcidin . In ACKD2 - 4 ( R(2 ) = 0.78 ) , ferritin and soluble transferrin receptor were associated with hepcidin , whereas GFR was inversely correlated . In PCKD5D ( R(2 ) = 0.52 ) , percent iron saturation and ferritin were predictors of hepcidin . In a multivariate analysis that incorporated all three groups ( R(2 ) = 0.6 ) , hepcidin was predicted by ferritin , C-reactive protein , and whether the patient had stage 5D versus stages 2 to 4 CKD . CONCLUSIONS These findings suggest that increased hepcidin across the spectrum of CKD may contribute to abnormal iron regulation and erythropoiesis and may be a novel biomarker of iron status and erythropoietin resistance INTRODUCTION Although clinical use of recombinant human erythropoietin ( rHuEPO ) since 1989 has improved anemia in most end-stage renal disease patients , there are still many hemodialysis patients unable to maintain an adequate hematocrit ( HCT ) without large doses of rHuEPO . This suggests that anemia is not solely a consequence of rHuEPO deficiency , but may be due to other factors including functional iron deficiency . Since the optimal prescription for iron replacement is not yet known , we evaluated the effect of intravenous iron dextran ( IVFe ) infusion on serum ferritin ( SFer ) concentration and rHuEPO dose . Our objective was to raise and maintain serum ferritin concentrations to 2 different levels above the National Kidney Foundation Dialysis Outcome Quality Initiative st and ard of 100 ng/ml to determine whether , and by what degree rHuEPO dose could be lowered . METHODS HD patients on i.v . rHuEPO with a SFer concentration > or = 70 ng/ml and an HCT of < or = 33 % were enrolled . Subjects were divided as follows : Group 1 : target SFer of 200 ng/ml , Group 2 : target SFer of 400 ng/ml . Each subject below the target level received IVFe in up to 10 divided doses during consecutive dialysis sessions as needed to reach the target . HCT was maintained between 32.5 % and 36 % by adjusting rHuEPO dosage . RESULTS Mean SFer concentration at the study conclusion in Group 1 : 261 ng/ml ; Group 2 : 387 ng/ml . The mean decrease in rHuEPO dose for Group 1 was 31 U/kg body weight/week ( 250 - 219 U/kg bw/wk ) while in Group 2 it was 154 U/kg body weight/week ( 312 - 158 U/kg bw/wk ) ( p < 0.001 ) . There was no difference in HCT between groups . Our results suggest that higher target serum ferritin concentrations can be well tolerated and lower rHuEPO requirements In view of current uncertainty regarding the optimum route for iron supplementation in patients receiving recombinant human erythropoietin ( EPO ) , a prospect i ve r and omized controlled study was design ed to investigate this issue . All iron-replete renal failure patients commencing EPO who had a hemoglobin concentration < 8.5 g/dl and an initial serum ferritin level of 100 to 800 micrograms/liter were r Output:	Significant reductions in ESA dosing may be achieved with optimal intravenous iron usage in the haemodialysis population , and suboptimal iron use may require higher ESA dosing to manage anaemia
MS2933	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND & AIMS The role of omeprazole in triple therapy and the impact of Helicobacter pylori resistance on treatment outcome are not established . This study investigated the role of omeprazole and influence of primary H. pylori resistance on eradication and development of secondary resistance . METHODS Patients ( n = 539 ) with a history of duodenal ulcer and a positive H. pylori screening test result were r and omized into 4 groups . OAC group received 20 mg omeprazole , 1000 mg amoxicillin , and 500 mg clarithromycin ; OMC group received 20 mg omeprazole , 400 mg metronidazole , and 250 mg clarithromycin ; and AC ( amoxicillin , 1000 mg , and clarithromycin , 500 mg ) and MC ( metronidazole , 400 mg , and clarithromycin , 250 mg ) groups received no omeprazole . All doses were administered twice daily for 1 week . H. pylori status was assessed before and after therapy by 13C-urea breath test . Susceptibility testing was performed at entry and in patients with persistent infection after therapy . RESULTS Eradication ( intention to treat [ n = 514]/per protocol [ n = 449 ] ) was 94%/95 % for OAC , 26%/25 % for AC ( P < 0.001 ) , 87%/91 % for OMC , and 69%/72 % for MC ( P < 0.001 ) . Primary resistance was 27 % for metronidazole , 3 % for clarithromycin , and 0 % for amoxicillin . Eradication in primary metronidazole-susceptible/-resistant strains was 95%/76 % for OMC and 86%/43 % for MC . Secondary metronidazole and clarithromycin resistance each developed in 12 patients : 8 treated with omeprazole and 16 without omeprazole . CONCLUSIONS Addition of omeprazole achieves high eradication rates , reduces the impact of primary resistance , and may decrease the risk of secondary resistance compared with regimens containing only two antibiotics S‐mephenytoin 4’‐hydroxylase ( CYP2C19 ) catalyses the metabolism of rabeprazole to some extent . Based on the metabolic and pharmacokinetic differences among other proton pump inhibitors such as omeprazole , lansoprazole and pantoprazole , rabeprazole appears to be the least affected proton pump inhibitor by the CYP2C19‐related genetic polymorphism Objective Helicobacter pylori treatment failure is thought to be due mainly to polymorphic cytochrome P450 2C19 ( CYP2C19 ) genetic polymorphism , associated with proton pump inhibitor metabolism , and antimicrobial susceptibility . This report has ascertained which was more important , CYP2C19 polymorphism or antimicrobial susceptibility , when using 1-week lansoprazole-based or rabeprazole-based triple therapy in Japan . Design An open , r and omized , parallel group study . Setting One hundred and forty-five subjects with H. pylori-positive gastritis or peptic ulcers were r and omly assigned to receive 30 mg lansoprazole twice daily ( LAC group ) , 10 mg rabeprazole twice daily ( RAC20 group ) , or 20 mg rabeprazole twice daily ( RAC40 group ) , with 1000 mg amoxicillin twice daily and 400 mg clarithromycin twice daily for 1 week . Antimicrobial resistance testing was performed by E-test . More than 4 weeks after completion of treatment , H. pylori status was assessed by 13C-urea breath test , histology , and culture . Results Cure rates expressed as intention-to-treat and per- protocol analyses , respectively , were 79.6 and 83.0 % with LAC , 85.4 and 89.1 % with RAC20 , and 83.3 and 88.9 % with RAC40 . In the case of clarithromycin-sensitive strains , the cure rates were more than 97 % , regardless of CYP2C19 polymorphism . However , treatment succeeded in only one out of 16 clarithromycin-resistant strains . Conclusions The key to successful eradication of H. pylori , using lansoprazole or rabeprazole with clarithromycin and amoxicillin , is clarithromycin susceptibility , not CYP2C19 polymorphism Aim : To investigate the effect of different proton pump inhibitors , S‐mephenytoin 4′‐hydroxylase ( CYP2C19 ) genotype and antibiotic susceptibility on the eradication rate of Helicobacter pylori Output:	The systematic review published in this issue suggests that particularly for omeprazole in combination with amoxicillin or amoxicillin and clarithromycin the success rate is much lower when compared to other proton pump inhibitors ( PPIs ) .
MS2934	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: INTRODUCTION The aim of this study was to investigate the duration of m and ibular-crowding alleviation with self-ligating brackets compared with conventional appliances and the accompanying dental effects . METHODS Fifty-four subjects were selected from a pool of patients satisfying the following inclusion criteria : non extraction treatment in the m and ibular or maxillary arches ; eruption of all m and ibular teeth ; no spaces in the m and ibular arch ; irregularity index greater than 2 in the m and ibular arch ; and no therapeutic intervention planned with any extraoral or intraoral appliance . The patients were r and omly assigned to 2 groups : 1 group received treatment with a self-ligating bracket ( Damon 2 , Ormco , Glendora , Calif ) and the other with a conventional edgewise appliance ( Microarch , GAC , Central Islip , NY ) , both with 0.022-in slots . The irregularity index of the m and ibular arch was normalized between the groups , and the time to alignment was estimated in days . Treatment duration was assessed by data modeling with the Cox proportional hazard regression . Lateral cephalometric radiographs were used to assess the alteration of m and ibular incisor position before and after alignment . Measurements of intercanine and intermolar widths were also made on dental casts to determine changes associated with correction . RESULTS AND CONCLUSIONS Overall , no difference in the time required to correct m and ibular crowding with Damon 2 and conventional brackets was observed . For moderate crowding ( irregularity index < 5 ) , however , the self-ligating group had 2.7 times faster correction . This difference was marginally insignificant for subjects with irregularity index scores greater than 5 . Greater crowding prolonged treatment by an additional 20 % for each irregularity index unit . Increases in intercanine and intermolar widths associated with crowding correction regardless of bracket group were noted . The self-ligating group showed a statistically greater intermolar width increase than the conventional group . Also , an alignment-induced increase in the proclination of the m and ibular incisors was observed for both bracket groups , but no difference was found between Damon 2 and conventional brackets for this parameter In a clinical trial involving 155 dental arches with irregularity > 5 mm , the rate of alignment was used to compare the alignment efficiency of 16 mil superelastic Ni-Ti versus 17.5 mil triple-str and ed steel archwires , and to determine whether ion implantation of the Ni-Ti wire improved its performance . Subjects were r and omly assigned to archwire types ; both 18 and 22 slot edgewise appliances were employed . Pre-treatment equivalence of the experimental groups was verified . Anterior irregularity was determined monthly ( using Little 's irregularity index ) until it decreased below 2 mm , and the elastomeric ligatures were replaced at each appointment . Effective tooth movement occurred with each of the archwire types . There were no significant differences among wires , but the rate of alignment was significantly faster in the lower arch for subjects with the 22 slot appliance Two arch wires commonly used for initial tooth alignment were compared with regard to their clinical effectiveness . The two arch wires tested were 0.0155-inch diameter multiple-str and ed stainless steel wire ( Dentaflex , Dentaurium , Optident , Yorkshire , Engl and ) and 0.014-inch diameter nickel-titanium alloy wire ( NiTi , ORMCO Co. , Monrovia , Calif. ) . Consecutive patients attending an orthodontic clinic for routine placement of a fixed appliance were r and omly assigned one of these two initial arch wires . Good quality alginate impressions of the appropriate dental arch were taken before arch wire placement and also at the subsequent appointment , which was , on average , 6 weeks later . Seventy-four arches were used in this study . The degree of tooth alignment achieved for each wire type was compared with a Reflex Microscope ( Reflex Measurement Ltd. , Butleigh , Engl and ) to make detailed measurements on the result ant casts . The degree of initial alignment achieved with the two wires was similar over this 6-week period . However , some differences were found for the lower labial segment where the interbracket span is usually reduced and where the superelastic nickel-titanium wire was found to give improved alignment . No threshold of crowding was found where one arch wire performed better than the other Two nickel-titanium archwire types commonly used for initial tooth alignment were compared with regard to the pain/discomfort patients experience during the initial phase of tooth movement . The two archwires used were a superelastic nickel-titanium alloy , 0.014 inch Sentalloy , Light ( GAC International Inc. Central Islip , NY , USA ) and a 0.014 inch Nitinol ( unitek , Monrovia , CA , USA ) , a conventional nickel-titanium aligning archwire . One hundred and twenty-eight consecutive patients attending an orthodontic university clinic and 2 private practice s for routine placement of a fixed appliance were r and omly assigned one of these 2 initial archwires . Assessment s of pain/discomfort were made daily by means of a 100 mm visual analog scale ( VAS ) over the first 7-day period after bonding . On the first day , recordings were made every hour for the first 11 hours . The results showed that the level of discomfort increased continuously every hour after the insertion of either a Sentalloy or a Nitinol as first archwires , with a peak in the first night , remaining high on the second day and decreasing thereafter to baseline level after 7 days . During the first 10 hours it was apparent that the pain/discomfort experienced after placement of a Sentalloy was less than that found with the Nitinol archwire , although a significant difference could be found at 4 hours only . No significant gender-specific differences were found in either archwire group . A significant difference between the upper and lower dental arches was observed during the first 11 hours after placement of either a Sentalloy or a Nitinol archwire , with the lower arch having the higher pain experience . ZusammenfassungZwei verschiedene Bögen aus NiTi-Legierungen , die häufig für die initiale Nivellierung verwendet werden , wurden in Hinsicht auf das Auftreten von Schmerzen/Beschwerden zu Beginn der Zahnbewegung untersucht . Das eine Bogen material war eine superelastische NiTi-legierung , 0,014 inch Sentalloy , Light ( GAC International Inc. , Central Islip , N. Y. ) , das and ere ein herkömmlicher 0,014 inch Nitinol-Bogen ( Unitek , Monrovia , Kalifornien).128 fortlaufend beh and elte Patienten aus einer kieferorthopädischen Universitätsklinik und zwei privaten Praxen , bei denen routinemäßig eine Multib and apparatur eingesetzt werden sollte , wurden r and omisiert für den einen oder den and eren Bogen vorgesehen . Die Beurteilungen der Schmerzen/Beschwerden wurden täglich während der ersten sieben Tage nach dem Einsetzen der festsitzenden Apparatur auf einer visuellen Skala von 100 mm Länge ( visual analogue scale , VAS ) vorgenommen . Zusätzlich wurde am ersten Tag für die ersten elf Stunden nach dem Einsetzen stündlich die Schmerzintensität aufgezeichnet . Die Ergebnisse zeigten , daß die Beschwerden für den ersten Bogen , sowohl für den Sentalloy-als auch für den Nitinol-Bogen , kontinuierlich jede Stunde nach dem Einsetzen anstiegen . Der Höhepunkt wurde in der ersten Nacht erreicht , blieb am zweiten Tag auf derselben Höhe und verringerte sich kontinuierlich bis zum siebten Tag auf das individuelle Ausgangsniveau . Während der ersten zehn Stunden war es offensichtlich , daß nach der Eingliederung der Bögen beim Sentalloy-Bogen deutlich geringere Beschwerden auftraten als bei dem Nitinol-Bogen ; dieser Unterschied war jedoch nur für die ersten vier Stunden signifikant . Keine signifikanten Unterschiede der Beschwerden zwischen den Bogen material ien f and en sich hinsichtlich des Geschlechts der Patienten . Ein signifikanter Unterschied wurde zwischen dem Ober- und dem Unterkiefer während der ersten elf Studen nach dem Einsetzen sowohl des Sentalloy- als auch des Nitinol-Bogens beobachtet ; i m Unterkiefer traten deutlich stärkere Beschwerden auf The aim of this study was to compare three orthodontic archwire sequences . One hundred and fifty-four 10- to 17-year-old patients were treated in three centres and r and omly allocated to one of three groups : A = 0.016-inch nickel titanium ( NiTi ) , 0.018 x 0.025-inch NiTi , and 0.019 x 0.025-inch stainless steel ( SS ) ; B = 0.016-inch NiTi , 0.016-inch SS , 0.020-inch SS , and 0.019 x 0.025-inch SS ; and C = 0.016 x 0.022-inch copper ( Cu ) NiTi , 0.019 x 0.025-inch CuNiTi , and 0.019 x 0.025-inch SS . At each archwire change and for each arch , the patients completed discomfort scores on a seven-point Likert scale at 4 hours , 24 hours , 3 days , and 1 week . Time in days and the number of visits taken to reach a 0.019 x 0.025-inch SS working archwires were calculated . A periapical radiograph of the upper left central incisor was taken at the start of the treatment and after placement of the 0.019 x 0.025-inch SS wire so root resorption could be assessed . There were no statistically significant differences between archwire sequences A , B , or C for patient discomfort ( P > 0.05 ) or root resorption ( P = 0.58 ) . The number of visits required to reach the working archwire was greater for sequence B than for A ( P = 0.012 ) but this could not be explained by the increased number of archwires used in sequence The statistical methodology of health research experiments published in Lancet , the New Engl and Journal of Medicine , and Medical Care between 1975 and 1980 for the presence or absence of an error of experimental design and analysis was examined . The error is the result of inappropriately using patient-related observations as the unit of analysis to form conclusions about provider behavior or outcomes determined jointly by patients and providers . The error was present in 20 of 28 ( 71 % ) health care experiments addressing an issue of health provider professional performance . Its usual effect is to increase erroneously the power of an experiment to detect differences between experimental and control groups . It is likely that this type of error could be avoided by the explicit and prospect i ve definition of hypotheses and the population s to which they are intended to pertain Aim To compare the efficiency of orthodontic archwire sequences produced by three manufacturers . Design Prospect i ve , r and omized clinical trial with three parallel groups . Setting Private orthodontic practice in Caloundra , QLD , Australia Subjects and methods One hundred and thirty‐two consecutive patients were r and omized to one of three archwire sequence groups : ( i ) 3 M Unitek , 0·014 inch Nitinol , 0·017 inch × 0·017 inch heat activated Ni – Ti ; ( ii ) GAC international , 0·014 inch Sentalloy , 0·016 × 0·022 inch Bioforce ; and ( iii ) Ormco corporation , 0·014 inch Damon Copper Ni – Ti , 0·014 × 0·025 inch Damon Copper Ni – Ti . All patients received 0·018 × 0·025 inch slot Victory SeriesTM brackets . Outcome measures M and ibular impressions were taken before the insertion of each archwire . Patients completed discomfort surveys according to a seven‐point Likert Scale at 4 h , 24 h , 3 days and 7 days after the insertion of each archwire . Efficiency was measured by time required to reach the working archwire , m and ibular anterior alignment and level of discomfort . Results No significant differences were found in the reduction of irregularity between the archwire sequences at any time‐point ( T1 : P = 0·12 ; T2 : P = 0·06 ; T3 : P = 0·21 ) or in the time to reach the working archwire ( P = 0·28 ) . No significant differences were found in the overall discomfort scores between the archwire sequences ( 4 h : P = 0·30 ; 24 h : P = 0·18 ; 3 days : P = 0·53 ; 7 days : P = 0·47 ) . When the time‐points were analysed individually , the 3 M Unitek archwire sequence induced significantly less discomfort than GAC and Ormco archwires 24 h after the insertion of the third archwire ( P = 0·02 ) . This could possibly be attributed to the progression in archwire material and archform . Conclusions The archwire sequences were similar in alignment efficiency and overall discomfort . Progression in archwire dimension and archform may contribute to discomfort levels . This study provides clinical justification for three common archwire sequences in 0·018 × 0·025 inch slot brackets OBJECTIVES To examine whether the transition temperature of Cu-NiTi archwires has an effect on the tooth movement during the alignment phase of orthodontic treatment . DESIGN ' Split mouth ' design in r and omly selected patients . SETTING AND SAMPLE POPULATION The Department of Orthodontics , School of Dentistry , University of Aarhus . Fifteen r and omly selected patients with identical level of irregularity in the alignment phase of their treatment . Experiment Variable - Specially manufactured Cu-NiTi archwires for the upper arch were inserted . These consisted of two separate halves , each with its own transition temperature , respectively Output:	There is very weak unreliable evidence , based on one very small study ( n = 24 ) at high risk of bias , that coaxial superelastic NiTi may produce greater tooth movement over 12 weeks , but no information on associated pain or root resorption . There is insufficient evidence to determine whether or not there is a difference between either thermoelastic or CuNiTi and superelastic NiTi initial arch wires . AUTHORS ' CONCLUSIONS There is no reliable evidence from the trials included in this review that any specific initial arch wire material is better or worse than another with regard to speed of alignment or pain . There is no evidence at all about the effect of initial arch wire material s on the important adverse effect of root resorption . Further well- design ed and conducted , adequately-powered , RCTs are required to determine whether the performance of initial arch wire material s as demonstrated in the laboratory , makes a clinical ly important difference to the alignment of teeth in the initial stage of orthodontic treatment in patients
MS2935	*TASK* the task is to summarize an input biomedical literature in six sentences *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 r and omized controlled trials have demonstrated benefits of aldosterone antagonists for patients with heart failure and reduced ejection fraction ( HFrEF ) , they excluded patients with serum creatinine > 2.5 mg/dl , and their use is contraindicated in those with advanced chronic kidney disease ( CKD ) . In the present analysis , we examined the association of spironolactone use with readmission in hospitalized Medicare beneficiaries with HFrEF and advanced CKD . Of the 1,140 patients with HFrEF ( EF < 45 % ) and advanced CKD ( estimated glomerular filtration rate [ eGFR ] < 45 ml/min/1.73 m(2 ) ) , 207 received discharge prescriptions for spironolactone . Using propensity scores ( PSs ) for the receipt of discharge prescriptions for spironolactone , we estimated PS-adjusted hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) for spironolactone-associated outcomes . Patients ( mean age 76 years , 49 % women , 25 % African-American ) had mean EF 28 % , mean eGFR 31 ml/min/1.73 m(2 ) , and mean potassium 4.5 mEq/L. Spironolactone use had significant PS-adjusted association with higher risk of 30-day ( HR 1.41 , 95 % CI 1.04 to 1.90 ) and 1-year ( HR 1.36 , 95 % CI 1.13 to 1.63 ) all-cause readmissions . The risk of 1-year all-cause readmission was higher among 106 patients with eGFR < 15 ml/min/1.73 m(2 ) ( HR 4.75 , 95 % CI 1.84 to 12.28 ) than among those with eGFR 15 to 45 ml/min/1.73 m(2 ) ( HR 1.34 , 95 % CI 1.11 to 1.61 , p for interaction 0.003 ) . Spironolactone use had no association with HF readmission and all-cause mortality . In conclusion , among hospitalized patients with HFrEF and advanced CKD , spironolactone use was associated with higher all-cause readmission but had no association with all-cause mortality or HF readmission Objectives : Hemodialysis patients have a cardiovascular mortality rate of 20–40 times that of the general population . Aldosterone inhibition by spironolactone has exerted beneficial , prognostically significant cardiovascular effects in patients with heart failure maintained on hemodialysis or peritoneal dialysis . Our aim was to investigate spironolactone 's effect in non heart failure hemodialysis patients . Methods : Fourteen stable chronic hemodialysis patients ( nine men ) , 59.5 ± 3.1 years of age were evaluated in a sequential , fixed-dose , placebo-controlled study . Heart failure was diagnosed on the basis of signs and symptoms of heart failure or left ventricular ejection fraction less than 50 % . Following an initial 4-month period of placebo administration after each dialysis , patients received spironolactone ( 25 mg thrice weekly after dialysis ) for the next 4 months . Data were recorded at baseline , at the end of placebo administration , and at the end of spironolactone treatment and included endothelial function by forearm reactive hyperemia during venous occlusion plethysmography , cardiac autonomic status by heart rate variability in the time and frequency domain , blood pressure response , and echocardiographic and laboratory data . Results : Placebo induced no changes in the aforementioned parameters . Following spironolactone , salutary effects were observed in the extent and duration of reactive hyperemia ( P < 0.05 for both ) , as well as in heart rate variability ( P < 0.05 ) and blood pressure control ( P < 0.05 ) . No changes occurred in echocardiographically derived left ventricular dimensions or mass . Conclusion : Low-dose spironolactone therapy in clinical ly stable non heart failure hemodialysis patients is associated with favorable effects on cardiovascular parameters known to adversely affect survival , such as endothelial dysfunction and heart rate variability . Spironolactone treatment might benefit long-term cardiovascular outcome of such patients We performed this study to assess whether low dose spironolactone could be administered in hemodialysis ( HD ) patients with moderate to severe heart failure to improve cardiovascular function and reduce hospitalization without inducing hyperkalemia . We enrolled 16 chronic HD patients with moderate to severe heart failure and left ventricle ejection fraction : 5 45 % . In a double blinded r and omized placebo controlled study , one group of 8 patients received 25 mg of spironolactone after each dialysis session within six months , and the rest received a placebo . Echocardiography was performed on all the patients to assess ejection fraction and left ventricular mass during 12 hours after completion of hemodialysis at the beginning and the end of study . Serum potassium was measured predialysis every 4 weeks . The mean ejection fraction increased significantly more in spironolactone group during the study period than in the placebo group ( 6.2 + /- 1.64 vs. 0.83 + /- 4.9 , P= 0.046 ) . The mean left ventricular mass decreased in the spironolactone group , but increased significantly in the placebo group during the period ( -8.4 + /- 4.72 vs. 3 + /- 7.97 . 95 % , P= 0.021 ) . The incidence of hyperkalemia was not significantly increased in the study or controlled groups . In conclusion , we found in this study that administration of spironolactone in chronic HD patients with moderate to severe heart failure substantially improved their cardiac function and decreases left ventricular mass without development of significant hyperkalemia Aims Mineralocorticoid receptor antagonists ( MRAs ) improve outcomes in patients with heart failure and reduced left ventricular ejection fraction ( HFrEF ) , but their use is limited by hyperkalaemia and /or worsening renal function ( WRF ) . BAY 94 - 8862 is a highly selective and strongly potent non-steroidal MRA . We investigated its safety and tolerability in patients with HFrEF associated with mild or moderate chronic kidney disease ( CKD ) . Methods and results This r and omized , controlled , phase II trial consisted of two parts . In part A , the safety and tolerability of oral BAY 94 - 8862 [ 2.5 , 5 , or 10 mg once daily ( q.d . ) ] was assessed in 65 patients with HFrEF and mild CKD . In part B , BAY 94 - 8862 ( 2.5 , 5 , or 10 mg q.d . , or 5 mg twice daily ) was compared with placebo and open-label spironolactone ( 25 or 50 mg/day ) in 392 patients with HFrEF and moderate CKD . BAY 94 - 8862 was associated with significantly smaller mean increases in serum potassium concentration than spironolactone ( 0.04–0.30 and 0.45 mmol/L , respectively , P < 0.0001–0.0107 ) and lower incidences of hyperkalaemia ( 5.3 and 12.7 % , respectively , P = 0.048 ) and WRF . BAY 94 - 8862 decreased the levels of B-type natriuretic peptide ( BNP ) , amino-terminal proBNP , and albuminuria at least as much as spironolactone . Adverse events related to BAY 94 - 8862 were infrequent and mostly mild . Conclusion In patients with HFrEF and moderate CKD , BAY 94 - 8862 5–10 mg/day was at least as effective as spironolactone 25 or 50 mg/day in decreasing biomarkers of haemodynamic stress , but it was associated with lower incidences of hyperkalaemia and WRF ESRD treated with dialysis is associated with increased left ventricular hypertrophy , which , in turn , is related to high mortality . Mineralocorticoid receptor antagonists improve survival in patients with chronic heart failure ; however , the effects in patients undergoing dialysis remain uncertain . We conducted a multicenter , open-label , prospect i ve , r and omized trial with 158 patients receiving angiotensin-converting enzyme inhibitor or angiotensin type 1 receptor antagonist and undergoing peritoneal dialysis with and without ( control group ) spironolactone for 2 years . As a primary endpoint , rate of change in left ventricular mass index assessed by echocardiography improved significantly at 6 ( P=0.03 ) , 18 ( P=0.004 ) , and 24 ( P=0.01 ) months in patients taking spironolactone compared with the control group . Rate of change in left ventricular ejection fraction improved significantly at 24 weeks with spironolactone compared with nontreatment ( P=0.02 ) . The benefits of spironolactone were clear in patients with reduced residual renal function . As secondary endpoints , renal Kt/V and dialysate-to-plasma creatinine ratio did not differ significantly between groups during the observation period . No serious adverse effects , such as hyperkalemia , occurred . In this trial , spironolactone prevented cardiac hypertrophy and decreases in left ventricular ejection fraction in patients undergoing peritoneal dialysis , without significant adverse effects . Further studies , including those to determine relative effectiveness in women and men and to evaluate additional secondary endpoints , should confirm these data in a larger cohort Background Patients with chronic kidney disease ( CKD ) have high cardiovascular mortality and morbidity associated with increased arterial stiffness . Plasma aldosterone levels are increased in CKD , and aldosterone has been found to increase vascular inflammation and fibrosis . It was hypothesized that aldosterone receptor inhibition with eplerenone could reduce arterial stiffness in CKD stage 3–4 . Study Design The design was r and omized , open , parallel group . Measurements of arterial stiffness markers were undertaken at weeks 1 and 24 . Intervention 24 weeks of add-on treatment with 25–50 mg eplerenone or st and ard medication . Outcomes Primary outcome parameter was carotid-femoral pulse wave velocity ( cfPWV ) . Secondary outcomes were augmentation index ( AIx ) , ambulatory arterial stiffness index ( AASI ) and urinary albumin excretion . Results Fifty-four CKD patients ( mean eGFR 36 mL/min/1.73 m2 , SD 11 ) were r and omized . Forty-six patients completed the trial . The mean difference in cfPWV changes between groups was 0.1 m/s ( 95%CI : −1.0 , 1.3 ) , P = 0.8 . The mean difference in AIx changes between groups was 4.4 % ( 0.1 , 8.6 ) , P = 0.04 . AASI was unchanged in both groups . The ratio of change in urinary albumin excretion in the eplerenone group compared to the control was 0.61 ( 0.37 , 1.01 ) , P = 0.05 . Four patients were withdrawn from the eplerenone group including three because of possible side effects ; one was withdrawn from the control group . Mild hyperkalemia was seen on three occasions and was easily managed . Limitations The full planned number of patients was not attained . The duration of the trial may have been too short to obtain full effect of eplerenone on the arteries . Conclusions Add-on treatment with eplerenone in CKD stage 3–4 did not significantly reduce cfPWV . There may be beneficial vascular effects leading to attenuated pulse wave reflection . Treatment was well-tolerated . Trial Registration Clinical Trials.gov OBJECTIVES This study investigated the influence of baseline and worsening renal function ( WRF ) on the efficacy of spironolactone in patients with severe heart failure ( HF ) . BACKGROUND Renal dysfunction or decline in renal function is a known predictor of adverse outcome in patients with HF , and treatment decisions are often on the basis of measures of renal function . METHODS We used data from the RALES ( R and omized Aldactone Evaluation Study ) in 1,658 patients with New York Heart Association functional class III or IV HF and an ejection fraction < 35 % . Participants were r and omized to spironolactone 25 mg , which could be titrated to 50 mg , or placebo daily . Renal function ( estimated glomerular filtration rate [ eGFR ] ) was estimated by the Modification of Diet in Renal Disease equation . Worsening renal function was defined as a 30 % reduction in eGFR from baseline to 12 weeks post-r and omization . RESULTS Individuals with reduced baseline eGFR exhibited similar relative risk reductions in all-cause death and the combined endpoint of death or hospital stays for HF as those with a baseline eGFR > 60 ml/min/1.73 m(2 ) and greater absolute risk reduction compared with those with a higher baseline eGFR ( 10.3 % vs. 6.4 % ) . Moreover , WRF ( 17 % vs. 7 % for spironolactone and placebo groups , Output:	Conclusion MRA benefits CKD patients in terms of LVMI , all-cause mortality , and MACEs with no incidence of severe hyperkalemia .
MS2936	*TASK* the task is to summarize an input biomedical literature in six sentences *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 once daily gentamicin administration to the conventional twice daily dosage schedule by estimation of serum gentamicin concentrations ( SGC ) in neonates . DESIGN R and omized controlled trial . SETTING Medical college hospital . SUBJECTS Seventy three neonates of gestational age>32 weeks at risk or with clinical features of sepsis . METHODS The subjects were divided into preterm and term groups . Babies in each of these groups were r and omized to receive a single daily dose ( 4 mg/kg ) or a twice daily dose ( 2.5 mg/kg ) of injection gentamicin intravenously . Trough and peak SGC were estimated half an hour prior and one hour after the second dose . Statistical analysis was done using the equivalence method . RESULTS In preterm as well as term babies , the mean peak and trough gentamicin levels were comparable in the two regimens . There is statistically significant evidence to show that the effect of once daily and twice daily dosage is similar . CONCLUSION Once daily gentamicin administration is as effective as twice daily therapy and would be more cost effective This article reports the results of a four-year follow-up study initiated in 1970 on the long-term effects of gentamicin and kanamycin use in newborn infants . Audiometric , vestibular , and psychometric evaluations were performed on gentamicin-treated , kanamycin-treated , and untreated , matched control infants and children . No substantial sensorineural hearing loss or vestibular dysfunction was identified in these patients that could be attributed to aminoglycoside therapy . Performances on the Illinois Test of Psycholinguistic Abilities , Beery Test of Visual Motor Integration , the Peabody Picture Vocabulary Test , and on fine and gross motor examinations were comparable for the three study groups Fifty-four neonates were included and completed the study . Twenty-seven neonates were given 2.0 - 2.5 mg/kg of gentamicin twice daily while 27 neonates were given 4.0 - 5.0 mg/kg of gentamicin once daily . The twice daily dose and the once daily dose group had mean steady state gentamicin peak concentrations of 5.94 + /- 1.57 mg/l and 8.92 + /- 1.59 mg/l , respectively ( p<0.05 ) while their trough concentrations were 1.44 + /- 0.49 mg/l and 0.90 + /- 0.35 mg/l , respectively ( p<0.05 ) . There were 3 neonates ( 11.11 % ) in the twice daily dose group whose peak and trough level were not within the desirable therapeutic range , two patients with too high trough level ( > 2 mg/l ) and one with subtherapeutic peak level ( < 4 mg/l ) . Only one patient in the once daily group had undesirable trough level that was higher than 1.5 mg/l but less than 2 mg/l . Treatment with a once daily dose did not present more nephrotoxity than a twice daily dose regimen and had the tendency to have less effect on renal function . Once daily dosage can achieve the equivalent efficacy compared to a twice-daily dosage regimen . All neonates in twice daily and once daily dosage groups showed improvement in clinical outcome . Therefore , a once daily dose of gentamicin with 4.0 - 5.0 mg/kg could be an appropriate regimen in term neonates during the first 7 days of life . This regimen produces peak concentration that may have greater clinical efficacy and trough concentration with less toxicity than conventional dosing regimen Neonates , especially preterms , are known to have low glomerular filtration rates ( GFR ) . This may result in elevated trough concentrations during multiple administration of aminoglycosides ( AGs ) , potentially leading to nephro- and ototoxic reactions . The once-daily administration ( q.d . ) of AGs has been shown to be equally or better tolerated in adults and children than the conventional schedules ( twice daily , b.i.d . ; thrice daily , t.i.d . ) , while offering potential pharmacodynamic and nursing advantages . No data , however , are available for neonates . As a consequence , this pilot study was conducted in order to assess the tolerance of the once-a-day administration of amikacin in comparison with the twice daily dose regimen , in relation to the pharmacokinetics of the drug under these two schedules . 22 Male neonates ( gestational age > or = 34 weeks ; postnatal age < or = 2 days ) were r and omized to receive amikacin ( AK ) ( 15 mg/kg/day ) q.d . ( n = 10 ) or b.i.d . ( n = 12 ) together with ampicillin ( 50 mg/kg/12 h ) . AK plasma levels were measured at days 1 , 3 , 5 and 7 of treatment just before the next dose ( trough level ) and 1 h after completion of infusion ( peak level ) and after 3 and 6 h only at day 1 . Due to the small size of the sample s , no difference in efficacy could be assessed and was not the aim per se . Glomerular dysfunction was assessed by creatinine clearance , and tubular injuries by the urinary excretion of proteins ( retinol binding protein , beta 2-microglobulin , clara cell protein ( P1 ) and microalbumin ) , enzymes ( N-acetyl-beta-D-glucosaminidase , alkaline phosphatase , alanine aminopeptidase , and gamma-glutamyltransferase ) , and total phospholipids ( TPL ) in urine . Ototoxicity was assessed by brainstem auditory evoked potentials ( BAEPs ) at days 0 , 3 and 9 of therapy . Eight healthy neonates served as controls . All patients showed a normal and similar increase of GFR during the first postnatal days . Proteinuria did not increase , but enzymuria and TPL increased significantly during the treatment in both AK groups without significant difference between groups . BAEPs at day 9 were not significantly different between treated and untreated patients . We conclude from this pilot study that , in the absence of more toxicity , the q.d . administration of AK in neonates of > or = 34 weeks of gestational age may be recommended over its bid schedule in view of its potential advantages In a prospect i ve , r and omized trial of once-daily versus twice-daily intravenous or intramuscular dosing with gentamicin , 11 neonates received 5.0 mg/kg once daily and 15 received 2.5 mg/kg twice daily for 2 ro 3 days . The once-daily intravenous dosing group and the twice-daily intravenous or intramuscular dosing group , respectively , had mean steady-state gentamicin peak concentrations of 10.7 versus 6.6 micrograms/ml ( p < 0.05 ) , 6-hour postdosing concentrations of 4.7 versus 2.8 micrograms/ml ( p < 0.05 ) , trough concentrations of 1.7 versus 1.7 micrograms/ml , elimination half-life of 8.8 versus 5.4 hours ( p < 0.05 ) , and volume of distribution at steady state of 0.67 versus 0.46 L/kg . No nephrotoxic effects were identified in any group . Once-daily gentamicin therapy with 5.0 mg/kg in neonates achieves peak serum levels that are more suitable for optimal bacterial killing than those which traditional regimens achieve . Similar trough levels suggest that even larger doses and longer dosing intervals may be ideal in term neonates OBJECTIVE : There is no uniformity in the current recommendations of dosing regimen of gentamicin for neonates . We conducted a prospect i ve , r and omized , controlled trial to compare a once-daily dosing regimen to the twice-daily dosing regimen for neonates ≥2500 g during the first 7 days after birth . STUDY DESIGN : Infants ≥2500 g admitted to the Neonatal Intensive Care Unit and prescribed gentamicin for suspected bacterial infection were r and omized to receive either 4 mg/kg every 24 hours , study group ( n=20 ) , or a st and ard regimen of 2.5 mg/kg every 12 hours , control group ( n=21 ) . Serum gentamicin concentrations ( SGCs ) were followed and gentamicin pharmacokinetics calculated on all infants . RESULTS : Peak SGC 30 minutes after the first dose was 8.2±1.7 μg/ml in the study group , compared to 6.4±1.5 μg/ml in the control group ( p=0.001 ) . Ninety-five percent of study group infants , compared to 81 % of the control group , had peak SGCs in therapeutic range after the first dose . Peak SGC at 48 hours ( steady state ) was 8.9±1.5 in the study group and 6.8±1.1 in the control group ( p=0.0001 ) . On further analysis , a significantly higher percentage of infants in the study group , compared to the control group , had peak SGCs in higher therapeutic ranges of 6 to 12 μg/ml as well as 8 to 12μg/ml . None of the study infants , compared to six control infants , had trough SGCs ≥2 μg/ml at steady state . Thus , none of the study group infants , versus six of the control group infants , needed a dosing adjustment at 48 hours ( p=0.02 , Fisher 's exact test ) . CONCLUSION : We found that 4 mg/kg gentamicin given every 24 hours achieved significantly higher peak SGCs and safe trough concentrations in all infants , compared to the twice-daily regimen of 2.5 mg/kg . We suggest that SGCs may not need to be followed in term infants prescribed a short course of this once-daily regimen for suspected early-onset sepsis if renal functions are normal Objective . We developed a simplified gentamicin dosing protocol for all neonates using a loading dose and once-daily dosing that would have an equal or lower incidence of toxicity and an equal or improved effectiveness compared with a regimen with no loading dose that included use of divided daily dosing . Methods . All neonatal intensive care unit patients with a postnatal age ≤7 days and started on gentamicin therapy at the discretion of the attending neonatologist were evaluated in this comparative cohort study . All peak and trough serum drug levels ( SDL ) , pertinent demographic data , and markers of potential nephrotoxicity , ototoxicity , and cure were tracked prospect ively during 132 consecutive , nonr and omized courses of therapy on a new gentamicin protocol . These were compared with data retrieved retrospectively throughout 103 consecutive , nonr and omized courses of therapy in a control group . Results . Initial measured peak SDL were higher ( 7.8 ± 1.1 μg/mL vs 6.1 ± 1.0 μg/mL ) and trough SDL were lower ( 0.9 ± 0.2 μg/mL vs 2.7 ± 0.6 μg/mL ) in the protocol term subset , compared with the control term subset ( gestational age , ≥37 weeks ; weight , ≥2500 g ) . One hundred percent of the initial and maintenance peak SDL in term protocol neonates were 5 to 12 μg/mL ; compared with 84 % of the initial and 61 % of maintenance peak SDL in the term control group . One hundred percent of the initial and maintenance trough SDL were in the desired range of < 2 μg/mL in term protocol neonates ; compared with 70 % of the initial and 94 % of maintenance trough SDL in the term control group . No significant differences were found in any SDL in low birth weight neonates ( gestational age < 37 weeks or weight < 2500 g and > 1500 g ) in the protocol compared with the control group . The very low birth weight ( weight < 1500 g ) protocol neonates had a significantly higher mean initial trough SDL ( 2.3 ± 0.7 μg/mL vs 1.5 ± 0.6 μg/mL ) and a lower incidence of initial trough SDL < 2.0 μg/mL ( 30 % vs 95 % ) than very low birth weight neonates in the control group . No differences were seen between groups in incidence of significant rise in serum creatinine or failure of hearing screen . Conclusion . A loading dose followed by once-daily dosing was shown to result in SDL in the safe and therapeutic range in all term neonates in this study . In low birth weight neonates , this regimen result ed in peak and trough SDL throughout therapy that were similar to those observed in the control group . Delaying the initiation of maintenance once-daily dosing until 36 to 48 hours after the loading dose would be expected to result in a higher incidence of initial trough SDL in target range for very low birth weight neonates Twenty full term neonates with suspected bacterial infection were r and omly assigned to a once daily or a twice daily dosage regimen with gentamicin ( 4 mg/kg/day ) . Concomitantly all patients were treated with ampicillin ( 200 mg/kg/day ) . The gentamicin concentration time curves were analysed by an open two compartment model under steady state conditions on day 4 of treatment . The mean theoretical maximum serum concentration in the group taking gentamicin once daily ( 10.9 micrograms/ml ) was significantly higher than in the group taking it twice daily ( 7 Output:	Extended interval dosing of aminoglycosides in neonates is safe and effective , with a reduced risk of serum drug concentrations outside the therapeutic range
MS2937	*TASK* the task is to summarize an input biomedical literature in six sentences *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 patient tolerance and treatment efficacy of subcutaneous interferon ( IFN ) alpha 2a plus cryotherapy versus cryotherapy alone in treatment of primary anogenital ( AG ) warts . DESIGN --R and omised placebo controlled observer blind study . Statistical analysis was by chi square and Mann Whitney U tests . PATIENTS --60 patients with newly diagnosed AG warts . INTERVENTION--29 and 31 patients were treated with subcutaneous IFN alpha 2a plus cryotherapy or placebo injections plus cryotherapy , respectively . MAIN OUTCOME MEASURES -- Clinical presence or absence of AG warts . Patients wart-free at 8 weeks were asked to re-attend at 12 weeks ; those with persistent warts at 8 weeks were withdrawn from the study . RESULTS --At 8 weeks 60.7 % ( 17/28 patients ) of the IFN group and 67.9 % ( 19/28 patients ) of the placebo group were clinical ly wart-free ( not significant ) ; corresponding figures at 12 week review were 29.6 % ( 8/27 patients ) and 40 % ( 10/25 patients ) respectively ( not significant ) . There was no difference in treatment response between males and females . Recurrence of warts at three month review , in patients cleared of warts at 8 weeks , was seen in 50 % ( 8/16 ) and 37.5 % ( 6/16 ) of patients in the IFN and placebo groups respectively ( not significant ) . Multiple warts and the presence of perianal/anal canal warts , either alone or concurrent with warts on the genitalia , at first clinic attendance , were adverse prognostic indicators ( p less than 0.001 , and p = 0.05 respectively ) . Cervical human papilloma virus ( HPV ) infection , exophytic or sub clinical , was present in 58.3 % and 77.2 % of females in the IFN and placebo groups respectively , at trial entry . Although these lesions were not directly treated , colposcopic resolution was seen in 12.5 % of affected women , in both treatment groups , by the end of the 7 week treatment period . Systemic side effects were significantly more common in the IFN than in the placebo group , 50 % versus 10.7 % of patients ( p less than 0.01 ) . Severe influenza like symptoms occurred , after the first three injections only , in one patient treated with IFN ; all other reported side effects were mild . CONCLUSIONS --Subcutaneous IFN alpha 2a combined with cryotherapy is no more effective than cryotherapy alone in the treatment of primary AG warts . The presence of multiple warts and perianal/anal canal warts are adverse prognostic indicators OBJECTIVE : To determine whether the combination of systemically administered interferon alpha-2a and ablative surgery for the treatment of genital and /or perianal warts produces a 30 % or greater improvement in lasting response rate compared with a control group receiving a combination of placebo and ablative therapy . DESIGN : R and omised , triple-blind , placebo-controlled trial using 1 or 3 MIU of interferon alpha-2a or placebo administered subcutaneously three times weekly for 10 weeks in combination with ablative surgery . SETTING : International , multicentre study in 10 genitourinary medicine clinics . PATIENTS : Two hundred and fifty patients with anogenital warts . MAIN OUTCOME MEASURES : Lasting response at week 38 . RESULTS : St and ard efficacy analysis at week 38 showed a lasting response in 51 % ( 35/68 ) of 3 MIU interferon-treated patients , 48 % ( 30/63 ) of 1 MIU interferon-treated patients and 43 % ( 29/67 ) of placebo-treated patients . CONCLUSIONS : With the doses and regime described , treatment with interferon alpha-2a in combination with ablative therapy is not significantly superior in the treatment of anogenital warts than placebo and ablative therapy In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias 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 --The primary objective was to determine if six weeks treatment with subcutaneous interferon alpha-2a ( IFN ) and podophyllin 25 % W/V administered twice per week , preceded by IFN alpha-2a three times weekly for one week showed a greater complete response rate in patients with primary condylomata acuminata when assessed at week 10 than treatment with podophyllin and placebo injections in the same schedule . The secondary objective was to compare recurrence rates in complete responders at six months in the two treatment groups . DESIGN --R and omised , double-blind parallel group study . SETTING --Multicentre study in six genitourinary clinics within the U.K. PATIENTS --One hundred and twenty-four patients with primary anogenital warts . MAIN OUTCOME MEASURES --Complete response rate at week 10 , and recurrence rate at week 26 in complete responders . RESULTS --At week 10 analysis of the efficacy population showed complete response in 36 % ( 15/42 patients ) of IFN-treated group and 26 % ( 11/43 patients ) in the placebo group ( no significant difference ) . Analysis of the safety population at week 26 showed persistence of the complete response in 57 % ( 8/14 patients ) of the IFN-treated group and 80 % ( 12/15 patients ) of the placebo group ( no significant difference ) . Adverse effects were more common in IFN-treated patients , involved particularly application site reaction and malaise but were generally mild . CONCLUSIONS --At the dose and with the regime described treatment with IFN alpha-2a in combination with podophyllin is no more effective in the treatment of primary anogenital warts than podophyllin alone and is associated with more adverse events Sexually transmitted diseases caused by human papilloma viruses , such as condylomata acuminata , are increasing in incidence and are often difficult to treat because of their tendency to recur . Many reports in the literature document the usefulness of interferons topically or systemically in these diseases . A r and omized study was conducted to evaluate interferon Alfa-2b ( Intron A ) as adjuvant therapy following CO2 laser surgery of condylomata acuminata . A low-dose regimen was administered ( two courses with 1 million I.U. s.c . daily for 6 days with a 2-week interval between the courses ) and had hardly any side-effects . The recurrence rate in the therapy group was significantly reduced ( 42 % vs 81 % ) , so routine prophylaxis of recurrence with interferons in condylomata acuminata should be discussed Systemic treatment modalities for eradication of multiple therapy resistant genital warts are so far not available . In this study laser treated patients with multiple genital warts received postoperatively either interferon alpha-2b subcutaneously ( s.c . ) 5 x 10(6 ) IU or matching placebo three times weekly for four weeks . At the conclusion of the study , 6 - 8 weeks after discontinuation of therapy , a significantly higher cure rate was found in the group of interferon-treated patients ( 14 of 27 ( 52 % ) patients cured ) than among placebo treated patients ( 5 of 22 ( 23 % ) patients cured ) ( p less than 0.05 ) . The side effects of fever , chills , myalgia , headache and leukopenia occurred more commonly in the interferon treated group than in the placebo group . However , only three of 32 patients discontinued interferon therapy because of side effects . We conclude that the addition of s.c . administered interferon alpha-2b to laser treated patients with chronic therapy resistant genital warts is fairly well tolerated and that it significantly enhances the chance of eliminating the disease Skillful laser ablation can remove any volume of human papillomavirus-associated vulvar disease but can not prevent reactivation of the surrounding latent viral reservoir during postoperative healing . Conversely , interferon and 5-fluorouracil are relatively ineffective as primary therapies in clearing bulky lesions . In this study of 71 assessable patients , topical 5-fluorouracil and systemic interferon injections were used postoperatively . Success rates within the adjuvant 5-fluorouracil and laser alone arms were essentially the same ( 9 of 18 vs 8 of 20 ) . In contrast , outcome in the interferon group was significantly better than that for the other two arms combined ( 27 of 33 [ 82 % ] vs 17 of 38 [ 45 % ] ; chi 2 10.31 ; p less than 0.002 ) . Moreover , 18 of 21 failures ( 86 % ) in the first two arms and 3 of 6 failures ( 50 % ) in the interferon arm were " rescued " from the need for a second laser surgical procedure by crossover to either the 1 or 3 MIU interferon regimen . Results from this open-label , r and omized clinical trial suggest that even a relatively low dose of recombinant interferon , used in combination with effective surgical debulking , can markedly reduce the risk of postoperative recurrence Forty-nine subjects were enrolled in a study comparing two dosages of parenterally administered interferon (IFN)-beta in combination with cryotherapy for the treatment of anogenital warts . Subjects were r and omized to receive subcutaneous injections of either 2 x 10(6 ) or 4 x 10(6 ) IU/m2 of IFN-beta ( Biogen ) three times a week for a total of 6 weeks . Cryotherapy was administered concomitantly by aerosolization of liquid nitrogen at 10-day intervals . Systemic side- effects were modest in intensity and included fever , chills , myalgia , and headaches ( flu-like symptoms ) . During the first 2 weeks of therapy , they were more common in the high dose group than in the low dose group ( P = 0.02 ) . Using survival analysis , there was no significant difference between the two groups in rates of resolution of warts present at baseline ( P = 0.62 ) . However , the rate of new lesion formation during the study was significantly lower in the high dose group ( P = 0.04 ) In the GRADE approach , r and omized trials are classified as high quality evidence and observational studies as low quality evidence but both can be rated down if a body of evidence is associated with a high risk of publication bias . Even when individual studies included in best- evidence summaries have a low risk of bias , publication bias can result in substantial overestimates of effect . Authors should suspect publication bias when available evidence comes from a number of small studies most of which have been commercially funded . A number of approaches based on examination of the pattern of data are available to help assess publication bias . The most popular of these is the funnel plot ; all , however , have substantial limitations . Publication bias is likely frequent , and caution in the face of early results , particularly with small sample size and number of events , is warranted OBJECTIVE --To determine whether interferon alpha-2a , when utilised as adjuvant chemotherapy following ablation of condylomata acuminata ( genital warts ) by cryotherapy , is effective in the prevention of recurrences . DESIGN --R and omised , placebo-controlled , double-blind study . Statistical analysis was by 2-tailed Fisher 's Exact Test . PATIENTS --97 patients with recurrent condylomata acuminata . INTERVENTION--49 patients were treated with cryotherapy plus subcutaneously administered interferon alpha-2a , and 48 received cryotherapy plus placebo . Of these , 36 and 37 patients , respectively , completed the study and were evaluable . MAIN OUTCOME MEASURE-- Clinical eradication of condylomata for six months following adjuvant chemotherapy . RESULTS --By completion of the adjuvant chemotherapy , 10 ( 28 % ) interferon recipients and 16 ( 43 % ) placebo recipients experienced recurrences . At six months follow-up , 25 ( 69 % ) interferon and 27 ( 73 % ) placebo recipients experienced recurrences . In the six months following interferon therapy , only 31 % of interferon and 27 % of placebo recipients remained free of recurrences ( p = 0.99 ) . CONCLUSIONS --Interferon alpha-2a administered subcutaneously offers no benefit as a chemotherapeut Output:	Compared with placebo , adjuvant alpha- , beta- and gamma-interferon were generally not significantly superior in terms of complete clearance over the short , intermediate or long term , nor with regard to intermediate- or long-term recurrence . However , the low-dose subgroup of adjuvant alpha-interferon was significantly superior compared with placebo regarding intermediate-term complete clearance and recurrence . No significant differences were seen in these comparisons regarding efficacy . Overall , we found no reliable evidence favouring the systemic use of interferon after ablative treatment of AGW
MS2938	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Recommending increased physical activity facilitates long-term weight loss , but the optimal level of physical activity to recommend is unknown . OBJECTIVE The objective of the study was to evaluate the efficacy for long-term weight loss of recommendations for much higher physical activity than those normally used in behavioral treatments . DESIGN Overweight men and women ( n = 202 ) were r and omly assigned to either a st and ard behavior therapy ( SBT ) for obesity , incorporating an energy expenditure ( EE ) goal of 1000 kcal/wk , or to a high physical activity ( HPA ) treatment , in which the goal was an EE of 2500 kcal/wk . To help HPA treatment group participants achieve this high exercise goal , their treatment included encouragement to recruit 1 - 3 exercise partners into the study , personal counseling from an exercise coach , and small monetary incentives . RESULTS The HPA treatment group reported achieving higher mean ( + /- SD ) physical activity levels than did the SBT group at 6 mo ( EE of 2399 + /- 1571 kcal/wk compared with 1837 + /- 1431 kcal/wk ) , 12 mo ( EE of 2249 + /- 1751 kcal/wk compared with 1565 + /- 1309 kcal/wk ) , and 18 mo ( EE of 2317 + /- 1854 kcal/wk compared with 1629 + /- 1483 kcal/wk ) ( all P < 0.01 ) . Mean ( + /- SEM ) cumulative weight losses at 6 , 12 , and 18 mo in the HPA treatment group were 9.0 + /- 7.1 , 8.5 + /- 7.9 , and 6.7 + /- 8.1 kg , respectively . In the SBT group , the corresponding weight losses were 8.1 + /- 7.4 , 6.1 + /- 8.8 , and 4.1 + /- 7.3 kg , respectively . Between-group differences in weight loss were significant at 12 and 18 mo . CONCLUSION These results suggest that recommendations of higher levels of physical activity ( EE of 2500 kcal/wk ) promote long-term weight loss better than do conventional recommendations OBJECTIVE : To investigate the sustained effectiveness of a novel skill-based intervention for weight loss . DESIGN : R and omized , controlled trial . SUBJECTS : A total of 80 overweight/obese women living in Connecticut . MEASUREMENTS : Absolute weight difference measured in pounds and absolute change in body mass index ( BMI ) . Secondary outcomes included changes in food frequency question naire ( FFQ ) data and waist-to-hip ratio . RESULTS : In all 61 , 35 , and 34 % of study participants completed the 6- , 12- , and 24-month assessment s , respectively . At 6 months postintervention , both counseling-based ( CBI ) and skill-based ( SBI ) intervention groups had statistically significant decreases in absolute weight ( 4.0±3.6 and 1.7±3.0 kg , respectively ) . Compared to their baseline values , both CBI and SBI groups still maintained weight losses at 24 months ( 1.1±5.8 and 0.59±3.3 kg , respectively ) ; however , the differences were not statistically significant . FFQ results showed that , within the SBI group , there was a significant decrease ( P<0.05 ) in percent fat from baseline to 12 months and a nearly significant decrease in saturated fat from baseline to 24 months ( P=0.07 ) . CONCLUSIONS : Both the novel SBI and conventional dietary counseling demonstrated some residual weight loss benefit at 2 y. Effects of the SBI on dietary intake patterns are encouraging , and warrant further study Purpose of review This review highlights recent work evaluating the relationship between exercise , physical activity and physical and mental health . Both cross-sectional and longitudinal studies , as well as r and omized clinical trials , are included . Special attention is given to physical conditions , including obesity , cancer , cardiovascular disease and sexual dysfunction . Furthermore , studies relating physical activity to depression and other mood states are review ed . The studies include diverse ethnic population s , including men and women , as well as several age groups ( e.g. adolescents , middle-aged and older adults ) . Recent findings Results of the studies continue to support a growing literature suggesting that exercise , physical activity and physical-activity interventions have beneficial effects across several physical and mental-health outcomes . Generally , participants engaging in regular physical activity display more desirable health outcomes across a variety of physical conditions . Similarly , participants in r and omized clinical trials of physical-activity interventions show better health outcomes , including better general and health-related quality of life , better functional capacity and better mood states . Summary The studies have several implication s for clinical practice and research . Most work suggests that exercise and physical activity are associated with better quality of life and health outcomes . Therefore , assessment and promotion of exercise and physical activity may be beneficial in achieving desired benefits across several population s. Several limitations were noted , particularly in research involving r and omized clinical trials . These trials tend to involve limited sample sizes with short follow-up periods , thus limiting the clinical implication s of the benefits associated with physical activity . Abbreviations CAD : coronary artery disease ; COPD : chronic obstructive pulmonary disease ; CRP : cardiac rehabilitation program ; CVD : cardiovascular disease ; GMCB : group-mediated cognitive – behavioural ; HRQOL : health-related quality of life Signal detection methods were used to identify predictors of successful weight loss in 177 mildly to moderately overweight women and men assigned to one of two weight-loss programs . Predictors included initial demographic , physiological , behavioral , and psychosocial characteristics , and program type ( e.g. diet-only and diet-plus-exercise ) . Successful weight loss was defined as a loss of at least two units of body mass index at one year . Four subgroups were identified . Participants in the diet-plus-exercise program who were initially more satisfied with their bodies and did not have a history of repeated weight loss were most likely to succeed ( 63 % succeeded ) . In contrast , participants assigned to the diet-plus-exercise program who were either extremely dissatisfied with their bodies or who had a history of repeated weight loss were at similar risk for failure as participants in the diet-only program ( only 26 % to 35 % succeeded ) . The results underscore the potential utility of exploring these subgroups further to inform the development of new treatment strategies to increase the likelihood of success BACKGROUND Although it is known that plasma leptin concentrations correlate with the amount of adipose tissue in the body , little information is available on the long-term effects on leptin concentrations of changes in diet and exercise . OBJECTIVE We wanted to examine whether changes in dietary energy sources and exercise-mediated energy expenditure , alone or in combination , affect plasma leptin concentrations . DESIGN In a r and omized , 2 x 2 factorial trial , 186 men with metabolic syndrome were divided into 4 groups : diet , exercise , a combination of diet and exercise , and control . Data on dietary intake , physical fitness , and demographics were collected and plasma leptin concentrations were measured before and after a 1-y intervention period . RESULTS Plasma leptin concentrations , body mass index , and fat mass decreased in association with long-term reductions in food intake as well as increased physical activity . By adjusting for either body mass index or fat mass , we observed a highly significant reduction in plasma leptin concentration after both the diet and the exercise interventions . There was no interaction between the interventions , suggesting a direct and additive effect of changes in diet and physical activity on plasma leptin concentrations . CONCLUSION Long-term changes in lifestyle consisting of decreased intake of dietary fat and increased physical activity reduced plasma leptin concentrations in humans beyond the reduction expected as a result of changes in fat mass CONTEXT The prevalence of overweight and obesity in the United States remains high . Commercial weight loss programs may contribute to efforts to reduce the prevalence of overweight and obesity , although few studies have examined their efficacy in controlled trials . OBJECTIVE To test whether a free prepared meal and incentivized structured weight loss program promotes greater weight loss and weight loss maintenance at 2 years compared with usual care . DESIGN , SETTING , AND PARTICIPANTS A r and omized controlled trial of weight loss and weight loss maintenance in 442 overweight or obese women ( body mass index , 25 - 40 ) aged 18 to 69 years ( mean age , 44 years ) conducted at US institutions over 2 years with follow-up between November 2007 and April 2010 . INTERVENTION The program , which involves in-person center-based or telephone-based one-to-one weight loss counseling , was available over a 2-year period . Behavioral goals were an energy-reduced , nutritionally adequate diet , facilitated by the inclusion of prepackaged food items in a planned menu during the initial weight loss phase , and increased physical activity . Participants assigned to usual care received 2 individualized weight loss counseling sessions with a dietetics professional and monthly contacts . MAIN OUTCOME MEASURES Weight loss and weight loss maintenance . RESULTS Weight data were available at 24 months for 407 women ( 92.1 % of the study sample ) . In an intent-to-treat analysis with baseline value substitution , mean weight loss was 7.4 kg ( 95 % confidence interval [ CI ] , 6.1 - 8.7 kg ) or 7.9 % ( 95 % CI , 6.5%-9.3 % ) of initial weight at 24 months for the center-based group , 6.2 kg ( 95 % CI , 4.9 - 7.6 kg ) or 6.8 % ( 95 % CI , 5.2%-8.4 % ) for the telephone-based group , and 2.0 kg ( 95 % CI , 0.6 - 3.3 kg ) or 2.1 % ( 95 % CI , 0.7%-3.5 % ) for the usual care control group after 24 months ( P < .001 for intervention effect ) . CONCLUSION Compared with usual care , this structured weight loss program result ed in greater weight loss over 2 years . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00640900 CONTEXT Although commercial weight loss programs provide treatment to millions of clients , their efficacy has not been evaluated in rigorous long-term trials . OBJECTIVE To compare weight loss and health benefits achieved and maintained through self-help weight loss vs with a structured commercial program . DESIGN AND SETTING A 2-year , multicenter r and omized clinical trial with clinic visits at 12 , 26 , 52 , 78 , and 104 weeks conducted at 6 academic research centers in the United States between January 1998 and January 2001 . PARTICIPANTS Overweight and obese men ( n = 65 ) and women ( n = 358 ) ( body mass index , 27 - 40 ) aged 18 to 65 years . INTERVENTION R and om assignment to either a self-help program ( n = 212 ) consisting of two 20-minute counseling sessions with a nutritionist and provision of self-help re sources or to a commercial weight loss program ( n = 211 ) consisting of a food plan , an activity plan , and a cognitive restructuring behavior modification plan , delivered at weekly meetings . MAIN OUTCOME MEASURES Weight change was the primary outcome measure . Secondary outcomes included waist circumference , body mass index , blood pressure , serum lipids , glucose , and insulin levels . RESULTS At 2 years , 150 participants ( 71 % ) in the commercial group and 159 ( 75 % ) in the self-help group completed the study . In the intent-to-treat analysis , mean ( SD ) weight loss of participants in the commercial group was greater than in the self-help group at 1 year ( -4.3 [ 6.1 ] kg vs -1.3 [ 6.1 ] kg , respectively ; P<.001 ) and at 2 years ( -2.9 [ 6.5 ] kg vs -0.2 [ 6.5 ] kg , respectively ; P<.001 ) . Waist circumference ( P = .003 ) and body mass index ( P<.001 ) decreased more in the commercial group . Changes in blood pressure , lipids , glucose , and insulin levels were related to changes in weight in both groups , but between-group differences in biological parameters were mainly nonsignificant by year 2 . CONCLUSION The structured commercial weight loss program provided modest weight loss but more than self-help over a 2-year period Objectives : To describe participants ’ adherence to multiple components ( attendance , energy intake , fat gram , exercise goals , and self-monitoring eating and exercise behaviors ) of a st and ard behavioral treatment program ( SBT ) for weight loss and how adherence to these components may influence weight loss and biomarkers ( triglycerides , low density lipoproteins [ LDL ] , high density lipoprotein , and insulin ) during the intensive and less-intensive intervention phases . Methods : A secondary analysis of a r and omized clinical trial consisting of a SBT with either fat-restricted st and ard or lacto-ovo vegetarian diet . The 12-month intervention was delivered in 33 group sessions . The first six months reflected the intensive phase ; the second six months , the less-intensive intervention phase . We conducted the analysis without regard to treatment assignment . Eligible participants included overweight/obese adults ( N = 176 ; mean body mass index = 34.0 kg/m2 ) . The sample was 86.9 % female , 70.5 % White , and 44. Output:	For percentage weight change , no significant differences were found among the BMI classes . Conclusion Average weight change during lifestyle interventions only differs to a small extent among people with BMI between 25 and 40 kg m−2 . This implies that these interventions are equally appropriate for these BMI classes
MS2939	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: In the r and omized , placebo-controlled , physician-blinded Canadian cooperative trial of cyclophosphamide and plasma exchange , neither active treatment regimens ( group I : IV cyclophosphamide and prednisone ; group II : weekly plasma exchange , oral cyclophosphamide , and prednisone ) were superior to placebo ( group III : sham plasma exchange and placebo medications ) using the blinded , evaluating neurologists ' assessment s of disease course ( primary analysis ) . All patients were examined by both a blinded and an unblinded neurologist at each assessment in this trial . We compared the blinded and unblinded neurologists ' judgment of treatment response and analyzed the clinical behavior of patients who correctly guessed their treatment . The unblinded ( but not the blinded ) neurologists ' scores demonstrated an apparent treatment benefit at 6 , 12 , and 24 months for the group II patients ( not group I or placebo ; p < 0.05 , two-tailed ) . There were no significant differences in the time to treatment failure or in the proportions of patients improved , stable , or worse between the group II and group III patients who correctly guessed their treatment assignments and those who did not . Physician blinding prevented an erroneous conclusion about treatment efficacy ( false positive , type 1 error ) Post-tonsillectomy bacteremia is a well-recognized aetiological factor in streptococcal endocarditis , and prophylactic penicillin has been recommended to reduce its incidence in susceptible patients undergoing tonsillectomy . Recent studies have shown a change in the microflora and an increase in the number of penicillin-resistant organisms in the tonsils of patients undergoing tonsillectomy . The aim of this study was to assess the incidence of post-tonsillectomy bacteraemia , to identify the micro-organisms associated with it and to review the suitability of penicillin in prophylactic regimens . The relationship between positive blood cultures and several clinical parameters such as fever , vomiting , pharyngeal discomfort , or dysphagia was also analysed . Of the 102 patients included in the study , 41 ( 40.1 % ) had positive post-tonsillectomy blood cultures . Haemophilus influenzae were isolated from 23 ( 56 % ) of the positive cultures and Streptococcus viridans in 15 ( 36.5 % ) . Twenty-five per cent of H. influenzae produced beta-lactamase and only 30 % of streptococci of the viridans group were penicillin-sensitive . Positivity of the blood cultures was not related to fever , discomfort , surgical technique , type of tonsil , or any of the parameters studied . Bacteraemia seems to be related to traction of the tonsil before dissection rather than direct spread of bacteria into the opened vessels . Using a beta-lactamase stable antibiotic instead of penicillin for prophylaxis would be more appropriate OBJECTIVE Systemic antibiotics given during the first week after tonsillectomy appear to be effective in reducing postoperative morbidity . We assessed the effectiveness of perioperative topical antibiotic rinses in reducing posttonsillectomy morbidity . METHODS A r and omized , double-blinded , placebo-controlled pilot study of 36 patients undergoing tonsillectomy was used to evaluate the effects of a st and ard 7-day systemic regimen of perioperative intravenous ampicillin/oral amoxicillin and 2 single-day topical antibiotic regimens : ( 1 ) clindamycin ( Cleocin ) and ( 2 ) amoxicillin/clavulanate ( Augmentin ) and ticarcillin/clavulanate ( Timentin ) . RESULTS Mean aerobic and anaerobic oral bacterial counts were decreased in both topical treatment groups compared with the placebo group on the first postoperative day , achieving statistical significance with Augmentin/Timentin ( aerobic and anaerobic bacterial counts ) and Cleocin ( aerobic counts ) . Significantly less postoperative pain and mouth odor were reported for both Cleocin ( P = 0.014 and P = 0.005 , respectively ) and Augmentin/Timentin ( P = 0.026 and P = 0.05 , respectively ) topical treatment groups when compared with the placebo group . CONCLUSIONS Preliminary results indicate a reduction in oral bacterial counts and postoperative morbidity in adult patients receiving topical antibiotics compared with patients receiving placebo ; further investigation is warranted Pain and secondary haemorrhage are the commonest complications of adult tonsillectomy , occurring mostly in the community . This is a r and omized , double-blind , placebo-controlled , prospect i ve trial of the effect of perioperative amoxycillin on these complications . The incidence and severity of post-operative haemorrhage was measured . For the first 10 post-operative days patients provided a linear pain score , a record of GP visits , and their use of additional antibiotics and analgesics . Of 95 patients considered : 23 suffered a secondary haemorrhage ; 54 consulted their general practitioner ( GP ) because of pain ; additional antibiotics were used by at least 31 and additional analgesics by at least 41 . No significant differences were demonstrated between the active and placebo groups for any of these measures . This study demonstrates that secondary haemorrhage is common after adult tonsillectomy . Post-operative pain remains a major problem requiring frequent GP consultations . There appears to be no justification for the routine use of perioperative antibiotics OBJECTIVE To investigate the effect of fusafungine spray on pain and healing process after pediatric tonsillectomy . METHODS Sixty children with ages between 4 and 14 years underwent tonsillectomy or adenotonsillectomy . The patients were r and omly divided into three groups and each group consisted of 20 patients . Group 1 was treated with antibiotic ( amoxicillin-clavulanic acid ) plus analgesic ( acetaminophen ) , group 2 was treated with fusafungine plus analgesic ( acetaminophen ) and group 3 was treated with only fusafungine . The average ages were 7.8 + 3.4 , 6.6 + 2.9 , and 8.2 + 3.7 for groups 1 , 2 , and 3 , respectively . Clinical evaluations were made after the operation on the 1st ( T1 ) , 3rd ( T3 ) , 7th ( T7 ) , 10th ( T10 ) , and 14th days ( T14 ) . RESULTS There was no significant difference in post-operative pain between study groups on the post-operative 1st , 3rd , and 7th days ( P > 0.05 ) , a statistically significant difference was present between groups 1 and 3 , and groups 1 and 2 on the post-operative 10th and 14th day ( P = 0.018 and 0.037 , respectively ) . Pain was less in groups 2 and 3 than in group 1 on the 10th and 14th day . Also there was a significant difference in healing time of the tonsillary beds between groups 1 and 2 , and groups 1 and 3 on the 10th and 14th post-operative day ( P = 0.031 and 0.001 , respectively ) . Healing was better in groups 2 and 3 than in group 1 on the 10th and 14th day . CONCLUSION Fusafungine administration after tonsillectomy was found to be beneficial on post-operative pain and wound healing of tonsillary beds in pediatric population Tonsillectomy has been performed by a number of techniques . This double blind r and omized controlled study compares the technique of tissue coblation with bipolar dissection for the removal of tonsils in 10 adult patients with a history of chronic tonsillitis . A significant reduction in post-operative pain and more rapid healing of the tonsillar fossae were found in the side removed by tissue coblation . There were no episodes of primary or secondary haemorrhage on either side . This new technique for tonsil removal warrants further study OBJECTIVE To determine the current practice s of preoperative evaluation , surgical techniques , and postoperative treatment of pediatric adenotonsillectomy . STUDY DESIGN Forty-one-item survey measuring the frequency of different evaluations , procedures , and treatments performed , including selected case scenarios , with all items scored on a five-point ordinal scale ranking frequency . METHODS The entire membership of the American Society of Pediatric Otolaryngology ( ASPO ) and active fellows and members of the American Academy of Otolaryngology-Head and Neck Surgery ( AAO-HNS ) residing in New York state were anonymously surveyed through mail-in question naires . RESULTS History alone was the most frequent modality for diagnosing both adenoid enlargement and obstructive sleep apnea . The most common preoperative laboratory test ordered before an adenotonsillectomy is a complete blood cell count ; ASPO members ordered fewer preoperative laboratory tests than AAO-HNS members . Unipolar cautery is the most frequently used tonsillectomy technique , and curettage followed by cautery is the most popular adenoidectomy technique . Steroids are the most common intraoperative medication administered during an adenotonsillectomy , and office visits remain the most frequently used methods of assessing adenotonsillectomy patients postoperatively . CONCLUSIONS Although there are statistically significant trends uncovered by the survey , the results reflect a lack of consensus regarding adenotonsillectomy management . Further r and omized controlled trials or large-scale outcomes projects are much needed to evaluate critically the current practice s of pediatric adenotonsillectomies . Additional efforts may also be required to use the information from these studies in effecting changes in actual practice patterns , moving us toward a more evidence -based paradigm of treating pediatric adenotonsillar disease A prospect i ve study of 99 adults undergoing tonsillectomy was carried out to determine the pattern of post-operative pain , intake of medication and timing of return to work and normal swallowing . The differences in the pain scores , as measured by a visual analogue scale , between every third consecutive day following post-operative day four were found to be highly significant ( p < 0.001 ) . Sixty-six patients ( 66.6 per cent ) required medication in the form of analgesics and /or antibiotics after the first post-operative day . Sixty-four out of a total of 82 patients ( 78.2 per cent ) returned to work within 14 days of surgery . Ninety-six patients ( 97 per cent ) reported normal swallowing within 14 days of surgery . These results suggest that the majority of adult patients undergoing tonsillectomy can be appropriately advised pre-operatively regarding the probable pattern and duration of post-operative pain and the timescales they can expect to return to work and normal swallowing OBJECTIVES Tonsillectomy is one of the most commonly performed otolaryngologic procedures in the United States . Many options and controversies exist regarding techniques and peri-operative management . The purpose of the study was to examine current practice patterns among otolaryngologists regarding tonsillectomy . METHODS A 13 question survey regarding tonsillectomy techniques and peri-operative management was mailed to 10 % of r and omly selected board certified otolaryngologists of the AAO-HNS in the spring of 2002 . Four hundred and eighteen anonymously completed question naires were returned , for a response rate of 58.5 % . Statistical analysis of survey data was performed by means of cross tabulation and Pearson Chi-Square Calculation . RESULTS Monopolar electrocautery was the most common technique used among those surveyed ( 53.5 % ) . There was a significant correlation between choice of monopolar electrocautery and the cited reason for choice of technique being decreased blood loss ( P < 0.001 ) . There was no relationship between pediatric fellowship training and choice of technique . 97.7 % routinely admitted sleep apnea patients for post-operative observation . There was no significant correlation between practice setting ( tertiary versus community ) and type of post-operative monitoring for sleep apnea patients , with patients most commonly admitted to an intermediate care setting . CONCLUSION In our survey , the most common surgical technique for tonsillectomy was monopolar electrocautery , chosen for the reason of decreased blood loss Tonsillectomy continues to be a commonly performed operation in the pediatric age group . The postoperative period is often protracted and characterized by throat and ear pain , intermittent fever , foul odor from the oral cavity , and poor oral intake . Consequently , antibiotics are frequently prescribed in an effort to minimize these symptoms and /or avoid complications such as dehydration or secondary infection of the operative site . However , to our knowledge , no study to date has been performed to demonstrate the efficacy of antibiotic therapy in this setting . At the Children 's Hospital of Philadelphia , a prospect i ve , r and omized , double-blind study was undertaken in which ampicillin ( or placebo ) was administered intravenously at the time of surgery and for 12 to 24 hours postoperatively . The children then continued to receive oral amoxicillin therapy ( or placebo ) for an additional seven days . The patients were then evaluated for the incidence and severity of postoperative symptoms and complications . Intraoperative cultures of the oropharynx and tonsillar tissue , as well as cultures of the tonsillar fossa , were obtained following completion of one week of therapy . Our results indicate that ampicillin sodium/amoxicillin trihydrate therapy is well tolerated and safe in the nonallergic child and is effective in minimizing fever and other troublesome postoperative symptoms , such as pain , lassitude , mouth odor , and poor oral intake after tons Output:	Most did not find a significant reduction in pain with antibiotics . Similarly , antibiotics were mostly not shown to be effective in reducing the need for analgesics . The present systematic review , including meta-analyses for select outcomes , suggests that although individual studies vary in their findings , there is no evidence to support a consistent , clinical ly important impact of antibiotics in reducing the main morbid outcomes following tonsillectomy ( i.e. pain , need for analgesia and secondary haemorrhage rates ) .
MS2940	*TASK* the task is to summarize an input biomedical literature in six sentences *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 has been shown that lipid profiles do not differ between pancreas recipients with systemic and portal venous anastomosis . However , it is unclear whether venous drainage from the transplanted pancreas has an impact on recipient atherogenesis and if other factors should be considered . Increased concentration of proinsulin correlates with tachycardia and other risk factors for ischemic heart disease . The aim of this study was to compare proinsulin levels in different types of pancreatic graft venous drainage . Twenty-four simultaneous pancreas and kidney transplantation ( SPK ) recipients with systemic venous drainage ( group S , n = 12 ) and portal venous drainage ( group P , n = 12 ) under identical immunosuppressive treatment were prospect ively observed during 24 months . Following transplantation , only recipients with normoglycemia , normal HbA1c , and normal serum creatine were evaluated . Proinsulin was assessed in fasting state ; after glucagon stimulation ( Delta-proinsulin ) , and during oral 75-g glucose tolerance test twice : between 3 and 6 months and 12 to 24 months posttransplantation . All SPK patients had higher proinsulin concentration in fasting state compared with age-matched healthy controls . After stimulation , proinsulin level did not significantly differ between groups ; the type of the pancreas venous anastomosis did not change the release of proinsulin and should not have impact on cardiovascular risk factors Abstract A r and omized study of combined kidney-pancreas transplantation was performed on 30 insulin-dependent diabetic patients with end-stage renal disease to compare the consequences of pancreas transplantation with portal venous ( PV ) and systemic venous ( SV ) drainage . Fourteen patients ( SV group ) received systemically drained and sixteen ( PV group ) portally drained pancreas allografts . Enteric drainage was performed in both groups . The routine follow-up included documentation of the clinical course and detailed endocrine studies . At 1 year after transplantation , the patient survival rate was 92 % for the SV group and 96 % for the PV group ; the graft survival rate was 78 % and 82 % , respectively . Endocrine studies indicated no difference in fasting and stimulated glucose or in glycosylated hemoglobin between the two groups . In addition , no hyperinsulinemia and lipidic abnormalities were evidence d in either group Long-term studies are required to conclude whether PV and SV drainage in pancreas transplantation are equivalent in terms of patient and graft survival as well as metabolic consequences BACKGROUND Most pancreas transplants are performed with systemic venous delivery of insulin and bladder drainage of the exocrine secretions ( systemic-bladder [ S-B ] ) . To develop a more physiologic procedure , we performed pancreas transplantations with portal venous delivery of insulin and enteric drainage of the exocrine secretions ( portal-enteric [ P-E ] ) . METHODS During an 11-month period , we prospect ively alternated 32 consecutive pancreas transplant recipients to either S-B ( n = 16 ) or P-E ( n = 16 ) drainage with st and ardized immunosuppression . RESULTS Patient , kidney , and pancreas graft survival rates after simultaneous kidney-pancreas transplantation were 91 % S-B versus 92 % P-E , 91 % S-B versus 92 % P-E , and 82 % S-B versus 92 % P-E , respectively . Pancreas graft survival rates after solitary pancreas transplantation were 80 % S-B versus 75 % P-E. There were no graft losses either to immunologic or infectious complications in either group , but the incidence of acute rejection was slightly higher in the S-B group ( 44 % S-B vs 31 % P-E , P = NS ) . The cost and length of the initial hospital stay were similar between groups . The incidence of operative complications , major infections , and cytomegalovirus infections were likewise comparable . However , the S-B group was characterized by a slight increase in the number of readmissions , urinary tract infections , and urologic complications . Furthermore , metabolic acidosis and dehydration were more common in the S-B group . CONCLUSIONS Pancreas transplantation with P-E drainage can be performed with short-term results comparable to those of transplantation with S-B drainage Simultaneous pancreas‐kidney ( SPK ) transplantation is considered a valid therapeutic option for patient with type I diabetes mellitus and end‐stage diabetic nephropathy . This study was performed to determine whether the technique of pancreas venous drainage affects patient survival as well as graft survival and function . From October 1996 to April 1999 34 uremic patients with type I diabetes mellitus were r and omly assigned to two groups : the first group ( SV group=17 ) received SPK transplantation with systemic venous drainage , and the second group ( PV group=17 ) received pancreas allograft with portal drainage . A Roux‐en‐Y loop was performed in all the patients . Patient follow‐up included clinical course and metabolic studies . At 1 yr , patient survival rates were 88.2 % in the SV group and 94.1 % in the PV group while graft survival rate was 76.4 % in both groups . Several surgical complications were attributed to the enteric drainage without any graft failure in both groups . One venous thrombosis occurred in each group . No significant differences have been evidence d in kidney and pancreas function . The preliminary results of this r and omized trial did not evidence any significant differences between portal and systemic venous drainage of pancreas allograft Abstract : The impact of portal or systemic venous pancreas graft drainage on patient and graft outcome remains controversial . In the present study , the impact of venous drainage type on long‐term patient and graft survival is assessed . From July 1996 to December 2002 80 simultaneous pancreas‐kidney transplants were enrolled into a prospect i ve study : 44 received a pancreas allograft with portal ( P‐SPK group ) and 36 with systemic venous drainage ( S‐SPK group ) . Enteric exocrine drainage was performed in all recipients receiving the same immunosuppressive treatment . At one yr , the patient survival rates were 91.7 % and 95.5 % both for S‐SPK and P‐SPK groups , respectively ; no significant difference in survival was shown at any time point of the follow‐up . The one‐ , three‐ , five‐ , and eight‐yr pancreas survival rates were 75 % , 60.6 % , 56.7 % , and 44 % , respectively in the S‐SPK group compared to 88.6 % , 84.1 % , 78.4 % , and 31.3 % in the P‐SPK group . The one‐ , three‐ , five‐ , and eight‐yr kidney survival rates were 91.7 % , 78.15 % , 74.1 % , and 57.9 % , respectively in the S‐SPK group compared to 93.2 % , 88.6 % , 78.4 % , and 38.9 % in the P‐SPK group . Comparing the two groups , no significant difference was shown in the total number of surgical complications as well as in the number of each complication . No significant difference in long‐term outcomes between the two groups was shown , even if in S‐SPK group a higher incidence of pancreas graft loss has been reported and it was in part correlated to a higher number of graft thromboses Objective To test the hypothesis that pancreas transplantation using the more physiologic method of portal venous-enteric ( PE ) drainage could be performed without compromising patient and graft outcome , compared with the st and ard method of systemic venous-bladder ( SB ) drainage . Methods Between November 1995 and November 1998 , the authors prospect ively followed up 20 consecutive patients with SB drainage followed by 20 consecutive patients with PE drainage . All patients underwent simultaneous pancreas – kidney transplantation , and all were immunosuppressed with antilymphocyte serum , cyclosporin , azathioprine , and steroids . Results The actuarial patient survival rate at 1 year was 95 % in the SB group and 100 % in the PE group . Death-censored kidney graft survival was 100 % in both groups ; pancreas graft survival was 95 % in the SB group and 100 % in the PE group . The mean initial hospital stay was 15 days for both groups . However , during the first 6 months after transplantation , the SB group required more medical day-unit visits , mostly for treatment of metabolic acidosis and dehydration . The incidence of urinary tract infections was similar in both groups . The incidence of cytomegalovirus infections was significantly less in the PE group . The incidence of acute rejection was 37 % in the SB group and 15 % in the PE group . Mean serum creatinine levels 6 months after transplantation were significantly lower in the PE group than in the SB group . Glycemic control was excellent in both groups , but fasting serum insulin levels were significantly lower in the PE group . Conclusions The PE method of pancreas transplantation can be performed with excellent patient and graft outcomes Since 1995 , many centers have switched from bladder to enteric drainage of the exocrine secretions in simultaneous kidney-pancreas transplantation ( SKPT ) . Enteric exocrine drainage may be performed with either systemic ( systemic-enteric [ S-E ] ) or portal ( portal-enteric [ P-E ] ) venous delivery of insulin . Controversy exists regarding the optimal surgical technique . From March 1999 to May 2001 , a total of 297 SKPT patients were enrolled into a prospect i ve , multicenter , r and omized , open-label , comparative trial of two daclizumab dosing strategies versus no-antibody induction in combination with tacrolimus , mycophenolate mofetil , and steroids in SKPT recipients . Surgical techniques were center specific . A total of 171 patients ( 58 % ) underwent SKPT with S-E drainage , 96 ( 32 % ) with P-E drainage , and 30 ( 10 % ) with systemic-bladder ( S-B ) drainage . The two groups r and omized to daclizumab induction were similar with regard to surgical technique ( 64 % S-E , 25 % P-E , 11 % S-B drainage ) . Demographic and transplant characteristics and immunosuppression were similar among the three groups , except that more patients with P-E drainage did not receive antibody induction . At 6 months , no differences were seen in patient and graft survival rates , surgical complications including pancreas thrombosis , rates of rejection or infection , readmissions , and kidney and pancreas allograft function among the three different surgical techniques . The 6-month results of this multicenter study suggest no significant differences in outcomes in SKPT recipients according to surgical technique Objective To compare pancreas transplantation with systemic-enteric ( SE ) versus portal-enteric ( PE ) drainage in a prospect i ve fashion . Summary Background Data To improve the physiology of pancreas transplantation , the authors developed a new technique of portal venous delivery of insulin and enteric drainage of the exocrine secretions . Methods During a 26-month period , the authors prospect ively alternated 54 consecutive simultaneous kidney and pancreas transplants to either SE ( n = 27 ) or PE ( n = 27 ) drainage . The two groups were well matched for numerous characteristics . Maintenance immunosuppression in both groups consisted of tacrolimus , mycophenolate mofetil , and steroids . Results Patient survival rates were 93 % SE versus 96 % PE ; kidney graft survival rates were 93 % in both groups . Pancreas transplantation survival ( complete insulin independence ) was 74 % after SE versus 85 % after PE drainage with a mean follow-up of 17 months . The mean length of initial hospital stay was 12.4 days in the SE group and 12.8 days in the PE group . The SE group was characterized by a slight increase in the number of readmissions . The incidences of acute rejection ( 33 % ) and major infection ( 52 % ) were similar in both groups . The incidence of intraabdominal infection was slightly higher in the SE group . However , the early relaparotomy rate was similar between groups . The composite endpoint of no rejection , graft loss , or death was attained in 56 % of SE versus 59 % of PE patients . Conclusions These results suggest that simultaneous kidney and pancreas transplantation with SE or PE drainage can be performed with comparable short-term outcomes OBJECTIVE To determine the long-term effect of a functioning pancreas transplant on peripheral vasculopathy . DESIGN We compared the progression of peripheral vascular disease in 39 recipients of successful kidney-pancreas transplants ( KPT ) with 65 consecutive diabetic patients who received cadaver kidney transplants alone ( KTA ) during the same period in a nonr and omized , retrospective control study . The mean duration of follow-up was more than 4 years in both groups . SETTING Academic subspecialty referral practice Output:	Based on this systematic review and meta- analysis , there is no evidence of differences in outcomes or metabolic control in patients undergoing pancreatic transplant with portal venous drainage compared to the systemic venous drainage
MS2941	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: PURPOSE To compare the effect of static holds and continuous passive motion on stiffness and force relaxation of the soft tissue structures resisting ankle joint dorsiflexion . METHODS This study used a r and omized repeated measures trial design . Twenty-four asymptomatic subjects ( 15 males and 8 females ) with a mean age of 26 yr participated . A Kin-Com dynamometer was used to measure the stiffness and force relaxation response of tissues about the ankle joint in response to a plantar flexor stretch . A comparison was made of the response for a 1 x 60-s hold , 2 x 30-s holds , 4 x 15-s holds , and continuous passive motion for 60 s. All subjects undertook all conditions . The main outcome measures were 1 ) stiffness at the ankle joint as it moved to 80 % of the maximum range of dorsiflexion , and 2 ) the decrease in force at 80 % of the maximum range of motion of the ankle joint . RESULTS Stiffness was decreased significantly ( P < 0.05 ) for the continuous passive motion condition only . The mean magnitude of the decrease in stiffness was 16 % . Across hold times , force decreased significantly ( P < 0.05 ) . Bonferonni contrasts indicated that there was a significant difference ( P < 0.05 ) between the continuous passive motion condition and all other hold conditions . There were no significant differences ( P > 0.05 ) between the 4 x 15-s , 2 x 30-s , and 1 x 60-s holds . The magnitude of the decline in force was 10.5 % , 21.5 % , 21.7 % , and 19 % for the 0- , 15- , 30- , and 60-s holds , respectively . The greatest decreases in tension were achieved in the first 20 s of a hold . CONCLUSION If decreasing stiffness is a key aim of a stretching program , the findings indicate that continuous motion is more effective than holds . In contrast , if relaxation of peak tension is the main aim , then holds are most effective Objective : To establish if isokinetic and isotonic muscle stretch ( with or without weight-bearing ) of the ankle plantar flexors improves gait in hemiplegic patients . A further aim was to compare the effectiveness of these treatment methods . Design : A r and omized , parallel group prospect i ve study . Setting : A stroke rehabilitation unit . Subjects : Ambulatory hemiparetic stroke patients with mild to moderately severe muscle hypertonia of the lower limb and a group of healthy control subjects . Intervention : Subjects were r and omized to receive a single 20-min session of isokinetic muscle stretch or isotonic muscle stretch with or without weight-bearing . Outcome measures : Selected kinematic , kinetic and spatio-temporal gait parameters were measured at baseline , immediately after the muscle stretch and 24 h later . Results : Sixty-six patients and 21 healthy control subjects were recruited and completed the study . There were statistically significant differences between the patient groups and the healthy subjects on most of the gait parameters studied . However , the differences between the patient groups or between the three measurements over time for each type of muscle stretch did not reach statistical significance . Conclusions : A single session of isokinetic or isotonic muscle stretch ( with or without weight-bearing ) of the ankle plantar flexors has no clinical ly observable effect on the gait of hemiplegic stroke patients The purpose of this study was to compare the effects of cyclic versus sustained passive stretching with a mechanical device on resting hamstring muscles ' length . Group 1 subjects ( 5 men , 17 women ) underwent cyclic stretching of their right hamstring musculature , and Group 2 subjects ( 5 men , 16 women ) underwent sustained stretching of their right hamstring musculature . The stretching procedures were performed for 15 minutes on 5 consecutive days . A follow-up examination of the subjects ' relative knee flexion range of motion was made one week posttreatment . The Group 1 subjects had a mean ROM increase of 15.4 + /- 5.0 degrees after the five stretching treatments and maintained a mean ROM increase of 10.4 + /- 5.5 degrees on the follow-up examination ( p less than .001 ) . In Group 2 , the five stretching treatments result ed in a mean ROM increase of 13.4 + /- 4.4 degrees , and a mean increase of 7.9 + /- 4.0 degrees was maintained on the follow-up examination ( p less than .001 ) . Linear regression analysis revealed that initial ROM , sex , and treatment method significantly contributed to increases in ROM from Day 1 of treatment to the follow-up examination ( F = 6.04 ; df = 4,36 ; p less than .0008 ) . The cyclic stretching method result ed in a greater gain in ROM when the other variables were considered . Predicted values of ROM increases were also examined and discussed OBJECTIVE To determine the effect of 4 weeks of 30 minutes of daily stretching on ankle mobility in patients with recent spinal cord injuries ( SCIs ) . DESIGN Assessor-blinded r and omized controlled trial . SETTING Two spinal injury units in Sydney , Australia . PATIENTS Consecutive sample of 14 recently injured patients with paraplegia and quadriplegia . INTERVENTION Treated ankles were stretched continuously into dorsiflexion with a torque of 7.5 N x m for 30 minutes each weekday for 4 weeks . Contralateral ankles received no stretches . MAIN OUTCOME MEASURES Passive torque-angle curves for both ankles were obtained at study commencement , then at weeks 2 , 4 , and 5 ( ie , during , at the end of , and 1 week after the stretching program ) . Torque-angle measurements were obtained with the knee extended and flexed . Mean values for parameters ( baseline angle , angle at 10 N x m , slope ) describing the characteristics of the torque-angle curves were derived for each knee position . Changes from pretest to each subsequent test were calculated , as well as 95 % confidence intervals ( CIs ) for differences in these changes between stretched and controlled ankles . RESULTS The stretching intervention did not significantly change any of the 3 parameters describing the torque-angle curves of the ankle in either knee position . At the beginning of the study , the mean ( + /-SD ) angles obtained with the application of a st and ardized torque with the knee extended for the control and stretch ankles were 105 degrees ( + /- 10.4 degrees ) and 106 degrees ( + /- 9.8 degrees ) , respectively . After 4 weeks , these values were 106 degrees ( + /- 10.6 degrees ) and 107 degrees ( + /- 10.6 degrees ) ( mean difference in change of angle = 0 degrees ; 95 % CI , -3.3 degrees to 3.3 degrees ) . CONCLUSION Thirty minutes of daily stretching for 4 weeks does not significantly change ankle mobility in recently injured patients with SCIs BACKGROUND AND PURPOSE Ankle plantar-flexion contractures are a common problem following traumatic head injury . Although serial casting is used to correct and prevent ankle plantar-flexion contractures , treatment efficacy has not been evaluated using an experimental design . The aim of this research was to establish the effect of a regimen of casting combined with stretching on passive ankle dorsiflexion motion . SUBJECTS Nine people who had sustained traumatic closed head injuries and had limited dorsiflexion motion participated in the study . METHODS A crossover design was used in the study . Subjects were assigned to both experimental and control groups . Torque-controlled measurements of passive ankle dorsiflexion motion were obtained for all subjects before and after 1 week of casting combined with stretching , as well as before and after a 1-week control period . The order of the experimental and control conditions was r and omized . RESULTS Passive ankle dorsiflexion increased by a mean of 13.5 degrees ( SD = 9.3 ) during the experimental condition , as compared with a mean decrease of 1.9 degrees ( SD = 10.2 ) during the control condition . The difference between the experimental and control conditions was statistically significant . CONCLUSION AND DISCUSSION These findings suggest that casting combined with stretching is an effective method of correcting ankle plantar-flexion contractures in patients with traumatic head injuries The aims of this study are to vali date the hypertonia treatment/ assessment system and to quantify the immediate effect of prolonged muscle stretch ( PMS ) on the inhibition of ankle hypertonia in stroke patients . For PMS treatment , ankle plantarflexors were stretched with a constant torque in 25 subjects with hemiplegia and ankle plantarflexors hypertonia . Using the developed hypertonia treatment/ assessment system , the effects of the PMS treatment were quantified by comparing the reactive torque measurements of the ankle joint before and after the treatment sessions in terms of elastic ( elastic-inertia ) ( K(ei ) ) and viscous ( K(v ) ) components . It was shown that an application of PMS for 30 min using a constant stretching force , approximately 80 % of the torque measured at the maximal passive ROM dorsiflexion position , significantly reduces both components of the ankle joint torque ( P < 0.05 ) . The present results suggested that the application of PMS with a constant torque could reduce not only the elasticity of the hypertonic muscles , but also their viscosity in the stroke patients Reflex behavior and tension development in upper limb muscles were analyzed and comparisons made between the unaffected and spastic sides of patients with spastic hemiparesis . During sinusoidal ( 0.3‐Hz ) isometric or isotonic elbow tracking , with a control either of joint position or of torque , r and omly timed displacements were induced ( at one of three velocities ) stretching either the activated flexor or the extensor muscles . On the spastic side , exaggerated short‐latency reflexes were apparent , but in contrast , the amplitude of long‐latency electromyography ( EMG ) responses was reduced . The latter responses were differentially modulated on the unaffected side , predominantly by the acceleration signal during control of position and more by the velocity signal during control of torque , while the mode of muscle contraction ( isometric or isotonic ) had little influence on this behavior . This difference in reflex modulation was lost on the spastic side . The functional consequence of this reduced EMG modulation could be difficulty in performing finely controlled arm movements . The ratio of torque to EMG activity during displacements was higher for both background and reflex‐induced EMG on the spastic limb than on the unaffected side . This effect was more pronounced for the flexor than for the extensor muscles . Consequently , the development of spastic muscle hypertonia can not be attributed to an increase in EMG activity . It is suggested that secondary to a supraspinal lesion , mechanical muscle properties change in such a way that the activated spastic muscle develops more tension when it is stretched OBJECTIVE To investigate the effect of repeated feedback-controlled and programmed " intelligent " stretching of the ankle plantar- and dorsiflexors to treat subjects with ankle spasticity and /or contracture in stroke . DESIGN Noncontrolled trial . SETTING Institutional research center . PARTICIPANTS Subjects with spasticity and /or contracture after stroke . INTERVENTIONS Stretching of the plantar- and dorsiflexors of the ankle 3 times a week for 45 minutes during a 4-week period by using a feedback-controlled and programmed stretching device . MAIN OUTCOME MEASURES Passive and active range of motion ( ROM ) , muscle strength , joint stiffness , joint viscous damping , reflex excitability , comfortable walking speed , and subjective experiences of the subjects . RESULTS Significant improvements were found in the passive ROM , maximum voluntary contraction , ankle stiffness , and comfortable walking speed . The visual analog scales indicated very positive subjective evaluation in terms of the comfort of stretching and the effect on their involved ankle . CONCLUSIONS Repeated feedback-controlled or intelligent stretching had a positive influence on the joint properties of the ankle with spasticity and /or contracture after stroke . The stretching device may be an effective and safe alternative to manual passive motion treatment by a therapist and has potential to be used to repeatedly and regularly stretch the ankle of subjects with spasticity and /or contracture without daily involvement of clinicians or physical therapists Application of eccentric contractions and muscle stretch are clinical ly effective in reducing spasticity and increasing ROM ( 7 ) . This may be explained by a change in the excitability of motoneurons supplying the spastic muscle . Excitability of motoneurons can be indirectly assessed using the H-reflex . Experiments were performed on 20 normal subjects and 17 subjects with spasticity result ing from neurological disorder . Subjects were seated in a secure position and the ankle joint was moved from 30 degrees plantarflexion to 20 degrees dorsiflexion at a velocity of 30 degrees/sec . Sixty eccentric contractions of the triceps surae muscle were performed using a Kin-Com dynamometer ( Chattanooga Corp , Tennessee ) . Two protocol s were used : ( 1 ) eccentric contractions only , and ( 2 ) eccentric contractions with a 5s stretch of the relaxed triceps surae after each contraction . Two sets of 10 H-reflexes were collected from the soleus muscle before ( trial 1 & 2 ) and after ( trial 3 & 4 ) eccentric and eccentric + stretch protocol s. The mean peak to peak H-reflex amplitude was calculated for each trial and compared using ANOVA . Eccentric contractions result ed in a significant and maintained increase in the H-reflex in neurological compared to normal subjects ( P < 0.05 ) . Eccentric contractions in subjects with spasticity result ed in an increase in motoneur Output:	Results : There is a sufficient level of evidence to support the use of stretching as and effective techniques in rehabilitation . Conclusion : The review adds stronger underst and ing with regard to stretching considerations in rehabilitation following UMNs .
MS2942	*TASK* the task is to summarize an input biomedical literature in six sentences *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 relevance of the individual components of the Valve Academic Research Consortium (VARC)-2 criteria for periprocedural myocardial infa rct ion ( MI ) in transcatheter aortic valve implantation ( TAVI ) . The association between biomarkers and adverse procedural outcome has been established . However , the additive prognostic importance of signs and symptoms are more uncertain . Methods A total of 125 consecutive TAVI patients were prospect ively included in this study . Biomarkers for MI were analyzed and signs and symptoms according to VARC-2 criteria were collected from clinical records . Results The criteria of elevated biomarkers and of signs or symptoms were found in 27 ( 22 % ) and 32 ( 26 % ) of the patients , respectively . According to VARC-2 definition , 12 ( 10 % ) had MI . VARC-2 definition of MI , Troponin T ( TnT ) > 600 ng/L , and presence of signs or symptoms correlated with 6 months mortality , prolonged ICU stay , elevation of N-terminal prohormone brain natriuretic peptide , and renal impairment . No signs or symptoms were found in 7 ( 44 % ) of the patients who fulfilled the criterion of elevated TnT > 600 ng/L. In the group with positive TnT criterion , there were no significant differences between those with and without signs or symptoms in respect to levels of TnT ( 1014 [ 585–1720 ] ng/L versus 704 [ 515–905 ] ng/L , p = 0.17 ) or creatine kinase-MB ( 36 [ 25–52 ] μg/L versus 29 [ 25–39 ] μg/L , p = 0.32 ) . In the multivariate Cox regression analysis , TnT > 600 ng/L was the only significant independent variable associated with 6-months postprocedural mortality . Conclusions Myocardial injury in TAVI , measured with biomarkers , correlates well with adverse procedural outcome . In this study it is also the strongest predictor for early postprocedural mortality . The additional requirement of signs or symptoms for the diagnosis of MI results in omission of a considerable number of clinical ly significant MI AIM Risk assessment of patients undergoing transcatheter aortic valve implantation ( TAVI ) remains difficult . Biomarkers have been shown to provide potential prognostic information . Here , we aim ed to analyze whether the biomarker high-sensitivity Troponin T ( hsTNT ) could be used to improve risk stratification . METHOD We prospect ively enrolled 267 patients undergoing TAVI . Biomarkers ( hsTNT and NTproBNP ) were measured 1 day before , and 3 and 7 days postprocedure . All possible prognostic factors upon survival time were analyzed by Cox regression analysis . RESULTS A total of 259 patients ( mean age 82±6.1 years ) were available for complete follow-up . The median Logistic EuroSCORE ( Log ES ) and Log ES II were 21.16 % ( Q1=13.92 ; Q3=34.27 ) and 6.42 % ( Q1=3.89 ; Q3=11.07 ) , respectively . Median follow-up was 290 ( Q1=88 ; Q3=529 ) days . A total of 71 deaths occurred during follow-up , and the 30-day mortality was 5.8 % . Median baseline hsTNT was 27.4 pg/mL ( Q1=16.2 ; Q3=46 pg/mL ) . From all potential mortality-associated factors , only preprocedural hsTNT level ( P=.001 ) , elevated Log ES ( P=.03 ) as well as acute kidney injury ( P<.001 ) and chronic obstructive pulmonary disease ( COPD ) ( P=.039 ) emerged as independent prognostic parameters for adverse outcome . We also tested whether the Valve Academic Research Consortium-2 ( VARC-II ) cutoff for myocardial damage ( hsTNT peak value exceeding 15 × the upper reference limit + at least 50 % increase ) was of prognostic relevance . At 72-hours post-TAVI , 36.2 % of the patients matched these VARC-II criteria of myocardial damage . However , these patients did not display a difference in survival compared to patients without significant myocardial injury . CONCLUSION Elevated preprocedural hsTNT represents an independent risk predictor of all-cause death while periprocedural hsTNT elevation failed to show prognostic relevance Background —Postprocedural myocardial infa rct ion ( type 4a ) has been shown to be an adverse prognostic indicator after elective percutaneous coronary intervention ( PCI ) . The Cardiac Remote Ischemic Preconditioning in Coronary Stenting ( CRISP Stent ) study demonstrated that remote ischemic preconditioning reduced procedural symptoms , ECG ST-segment deviation , and cardiac troponin I release after elective PCI and reduced the major adverse cardiac and cerebral event ( MACCE ) rate at 6 months . We were interested to confirm if this early benefit in MACCE rate in the remote ischemic preconditioning group was sustained long-term . Methods and Results — Patients were telephoned by research ers blinded to the r and omization details . MACCE , defined as all-cause mortality , nonfatal myocardial infa rct ion , transient ischemic attack or stroke , and heart failure requiring hospital admission , were adjudicated by case note and national data base review . One hundred ninety-two ( 89.3 % ) of the 225 patients with elective PCI r and omized in the original study were available for long-term follow-up ( mean time to event or last follow-up : 1579.7±603.6 days ) . There were a total of 59 ( 30.7 % ) MACCEs . Patients with an MACCE had a higher mean cardiac troponin I after PCI ( ±SD ) : 2.07±6.99 versus 0.91±2.07 ng/mL ( P=0.05 ) . The MACCE rate at 6 years remained lower in the remote ischemic preconditioning group ( hazard ratio , 0.58 ; 95 % confidence interval , 0.35–0.97 ; P=0.039 ; absolute risk reduction=0.13 and number needed to treat=8 to prevent the MACCE at 6 years ) . Conclusions —Remote ischemic preconditioning reduces the incidence of postprocedural cardiac troponin I after elective PCI and confers an MACCE-free survival benefit at both short- and long-term follow-up . Clinical Trial Registration —URL : http://www.ukcrn.org.uk . Unique identifier : UKCRN Non-r and omised studies of the effects of interventions are critical to many areas of healthcare evaluation , but their results may be biased . It is therefore important to underst and and appraise their strengths and weaknesses . We developed ROBINS-I ( “ Risk Of Bias In Non-r and omised Studies - of Interventions ” ) , a new tool for evaluating risk of bias in estimates of the comparative effectiveness ( harm or benefit ) of interventions from studies that did not use r and omisation to allocate units ( individuals or clusters of individuals ) to comparison groups . The tool will be particularly useful to those undertaking systematic review s that include non-r and omised studies Background Elevated concentrations of troponin T have prognostic impact in patients with various cardiovascular diseases including those with severe aortic stenosis . Transcatheter aortic valve implantation ( TAVI ) has improved prognosis for patients without a surgical option . Whether this affects the prognostic value of preinterventional troponin T remains unclear . Methods We therefore conducted a prospect i ve study in 198 consecutive patients with subsequent , successful transfemoral TAVI and analyzed cardiac troponin T ( cTnT ) levels with a new generation , high-sensitive troponin T assay before and after TAVI , as well as their prognostic value after 12 months . Results Patients with severe aortic stenosis ( AS ) showed significant elevation of preinterventional cTnT levels . Postinterventional cTnT levels significantly rose further about sevenfold after transfemoral TAVI and peaked at day three until they steadily declined thereafter . Baseline renal function ( P = 0.011 ) , the duration of intraprocedural rapid pacing ( P = 0.0012 ) , and baseline cTnT ( P = 0.0001 ) values predicted the magnitude of postinterventional cTnT elevations . Interestingly , Kaplan – Meier curve analysis revealed , that although cTnT levels were not predictive for short-term mortality , preinterventional as well as postinterventional peak cTnT showed prognostic value for 1-year mortality , regardless of successful TAVI . Conclusions Pre- and postinterventional hscTnT levels signal adverse 1-year mortality in patients with severe AS independent of successful aortic valve replacement BACKGROUND Previous trials have shown that among high-risk patients with aortic stenosis , survival rates are similar with transcatheter aortic-valve replacement ( TAVR ) and surgical aortic-valve replacement . We evaluated the two procedures in a r and omized trial involving intermediate-risk patients . METHODS We r and omly assigned 2032 intermediate-risk patients with severe aortic stenosis , at 57 centers , to undergo either TAVR or surgical replacement . The primary end point was death from any cause or disabling stroke at 2 years . The primary hypothesis was that TAVR would not be inferior to surgical replacement . Before r and omization , patients were entered into one of two cohorts on the basis of clinical and imaging findings ; 76.3 % of the patients were included in the transfemoral-access cohort and 23.7 % in the transthoracic-access cohort . RESULTS The rate of death from any cause or disabling stroke was similar in the TAVR group and the surgery group ( P=0.001 for noninferiority ) . At 2 years , the Kaplan-Meier event rates were 19.3 % in the TAVR group and 21.1 % in the surgery group ( hazard ratio in the TAVR group , 0.89 ; 95 % confidence interval [ CI ] , 0.73 to 1.09 ; P=0.25 ) . In the transfemoral-access cohort , TAVR result ed in a lower rate of death or disabling stroke than surgery ( hazard ratio , 0.79 ; 95 % CI , 0.62 to 1.00 ; P=0.05 ) , whereas in the transthoracic-access cohort , outcomes were similar in the two groups . TAVR result ed in larger aortic-valve areas than did surgery and also result ed in lower rates of acute kidney injury , severe bleeding , and new-onset atrial fibrillation ; surgery result ed in fewer major vascular complications and less paravalvular aortic regurgitation . CONCLUSIONS In intermediate-risk patients , TAVR was similar to surgical aortic-valve replacement with respect to the primary end point of death or disabling stroke . ( Funded by Edwards Lifesciences ; PARTNER 2 Clinical Trials.gov number , NCT01314313 . ) OBJECTIVES The aim of this study was prospect i ve investigation of silent and clinical ly apparent cerebral embolic events and neurological impairment after transfemoral aortic valve implantation ( TAVI ) . BACKGROUND TAVI is a novel therapeutic approach for multimorbid patients with severe aortic stenosis . We investigated peri-interventional cerebral embolism with diffusion-weighted magnetic resonance imaging ( DW-MRI ) and its relationship to clinical and serologic parameters of brain injury . METHODS Cerebral DW-MRI was performed before , directly , and 3 months after TAVI with the current third-generation self-exp and ing CoreValve ( Medtronic , Minneapolis , Minnesota ) prosthesis . At the timepoints of the serial MRI studies , focal neurological impairment was assessed according to the National Institutes of Health Stroke Scale ( NIHSS ) , and serum concentration of neuron-specific enolase ( NSE ) , a marker of the volume of brain tissue involved in an ischemic event , were determined . RESULTS Thirty patients were enrolled ; 22 completed the imaging protocol . Three patients ( 10 % ) had new neurological findings after TAVI , of whom only 1 ( 3.6 % ) had a permanent neurological impairment . Of the 22 TAVI patients with complete imaging data , 16 ( 72.7 % ) had 75 new cerebral lesions after TAVI presumed to be embolic . The NIHSS and NSE were not correlated with DW-MRI lesions . CONCLUSIONS The incidence of clinical ly silent peri-interventional cerebral embolic lesions after TAVI is high . However , in this cohort of 30 patients , the incidence of persistent neurological impairment was low . ( Incidence and Severity of Silent and Apparent Cerebral Embolism After Conventional and Minimal-invasive Transfemoral Aortic Valve Replacement ; NCT00883285 ) Output:	Conclusions : PPMI is common following TAVR and is strongly associated with 30-day and 1-year mortality . Detection of PPMI has potential to identify TAVR patients at highest risk of subsequent adverse events
MS2943	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Obesity has become a global public health problem , which also affects children . It has been proposed that the educational interventions during childhood could be a key strategy in the prevention of obesity . Objective To evaluate the efficacy of an intervention on food habits and physical activity in school children . Methods A 2-year cluster-r and omised prospect i ve study with two parallel arms was used to evaluate an intervention programme in children in their first year of primary schooling ( 5–6 years of age ) in schools in the city of Granollers . The intervention consisted of the promotion of healthy eating habits and physical activity by means of the educational methodology Investigation , Vision , Action and Change ( IVAC ) . At the beginning and at the end of the study ( 2006 and 2008 ) the weight and height of each child was measured in situ , while the families were given a self-report physical activity question naire and the Krece Plus quick test . Results Two years after the beginning of the study , the body mass index of the children in the control group was 0.89 kg/m2 higher than that of the intervention schools . The intervention reduced by 62 % the prevalence of overweight children . Similarly , the proportion of children that ate a second piece of fruit and took part in an after-school physical activity increased in the intervention group . In the control group , the weekly consumption of fish was reduced . Conclusions The educational intervention in healthy eating habits and physical activity in the school could contribute to lessen the current increase in child obesity Summary Background Although childhood overweight and obesity prevalence has increased substantially worldwide in the past three decades , scarce evidence exists for effective preventive strategies . We aim ed to establish whether a school-based intervention for children aged 9–10 years would prevent excessive weight gain after 24 months . Methods This pragmatic cluster r and omised controlled trial of the Healthy Lifestyles Programme ( HeLP ) , a school-based obesity prevention intervention , was done in 32 schools in southwest Engl and . All state-run primary and junior schools in Devon and Plymouth ( UK ) with enough pupils for at least one year-5 class were eligible . Schools were assigned ( 1:1 ) using a computer-generated sequence to either intervention or control , stratified by the number of year-5 classes ( one vs more than one ) and the proportion of children eligible for free school meals ( < 19 % [ the national average ] vs ≥19 % ) . HeLP was delivered to year-5 children ( ages 9–10 years ) over 1 year , and included dynamic and interactive activities such as physical activity workshops , education sessions delivered by teachers with short homework tasks , drama sessions , and setting goals to modify behaviour ( with parental support and one-to-one discussion s with HeLP coordinators ) . The primary outcome was change in body-mass index ( BMI ) st and ard deviation score ( SDS ) between baseline and 24 months , analysed in children with BMI data available for both timepoints . This study is registered with the International St and ard R and omised Controlled Trial register , number IS RCT N15811706 , and the trial status is complete . Findings Between March 21 , 2012 , and Sept 30 , 2013 , 32 eligible schools with 1324 children were recruited , of which 16 schools ( 676 children ) were r and omly assigned to the HeLP intervention and 16 schools ( 648 children ) to control . All schools that began the trial completed the intervention , and 1244 children ( 628 in intervention group and 616 in control group ) had BMI data at both baseline and 24 months for the primary outcome analysis . Mean BMI SDS was 0·32 ( SD 1·16 ) at baseline and 0·35 ( 1·25 ) at 24 months in the intervention group , and 0·18 ( 1·14 ) at baseline and 0·22 ( 1·22 ) at 24 months in the control group . With adjustment for school-level clustering , baseline BMI scores , sex , cohort , and number of year-5 classes and socioeconomic status of each school , the mean difference in BMI SDS score ( intervention – control ) at 24 months was −0·02 ( 95 % CI −0·09 to 0·05 ) , p=0·57 . One parent reported an adverse event related to their child 's eating and activity behaviours , but agreed for the child to continue trial participation after discussion with the chief investigator . Interpretation Despite a theoretically informed and extensively piloted intervention that achieved high levels of engagement , follow-up , and fidelity of delivery , we found no effect of the intervention on preventing overweight or obesity . Although schools are an ideal setting in which to deliver population -based interventions , school-based interventions might not be sufficiently intense to affect both the school and the family environment , and hence the weight status of children . Future research should focus on more upstream determinants of obesity and use whole-systems approaches . Funding UK National Institute for Health Research , Public Health Research Programme Few studies have investigated the impact of school-based physical activity interventions on anthropometric characteristics concomitantly with aerobic and anaerobic capacities in young children . The present study aim ed to assess the effect of a 6-month physical activity program on body composition and physical fitness among primary schoolchildren . Four hundred fifty-seven children aged 6 to 10 years were r and omly assigned to the intervention group ( 229 children ) or observational group ( 228 children ) . Participants ’ height and weight were assessed , and obesity was determined using French reference curves for BMI . The sum of the four skinfolds and fat-free mass were determined . Ground tests were used to assess aerobic ( 20-m shuttle run test ) and anaerobic ( cycling peak power ) fitness before and after a 6-month physical activity intervention . The anthropometric modifications obtained over the 6 months can not be attributed to the intervention as the ANOVA revealed no group effect ( intervention vs. group ) . However , anaerobic and aerobic fitness were significantly improved , thanks to the program in both lean and obese children . A 6-month school-based physical activity intervention in 6- to 10-year-old children did not yield positive anthropometric improvements , but appears effective in terms of aerobic and anaerobic physical fitness . Two physical activity sessions per week in addition to st and ard physical education classes in primary schoolchildren bring effective results for the prevention of childhood obesity Objective : To evaluate the effectiveness of the Shaping Healthy Choices Program ( SHCP ) . Design : A clustered , r and omized , controlled intervention lasting 1 school year . Setting : Schools in northern and central California . Participants : Fourth‐ grade rs ( aged 9–10 years ) at 2 control schools ( n = 179 ) and 2 intervention schools ( n = 230 ) . Intervention : Garden‐enhanced education , family , and community partnerships ; increased regionally procured produce in the lunchroom ; and school‐site wellness committees . Main Outcome Measures : Changes in body mass index ( BMI ) percentiles/Z‐scores ; nutrition knowledge , science process skills , and vegetable identification and preferences ; and reported fruit and vegetable intake . Analysis : Student t test , chi‐square , ANOVA of change , and multilevel regression mixed model to evaluate change in outcomes with school as a r and om effect to account for cluster design effects . Statistical significance was set at P < .05 . Results : There was a greater improvement in BMI percentile ( −6.08 ; P < 0.01 ) , BMI Z‐score ( −0.28 ; P < .001 ) , and waist‐to‐height ratio ( −0.02 ; P < .001 ) in the intervention compared with the control schools . Conclusions and Implication s : The SHCP result ed in improvements in nutrition knowledge , vegetable identification , and a significant decrease in BMI percentiles . This supports the concept that the SHCP can be used to improve the health of upper elementary school students The global rate of obesity in childhood is becoming an epidemic and many authors have established a significant association between childhood obesity and overweight in adulthood . It is therefore necessary to seek effective strategies to reduce these levels of obesity . The aim of this study was to evaluate the impact of the Healthy Habits Program ( HHP ) . The participants comprised 158 children from the fifth and sixth grade s ( intervention group , n = 82 ; control group , n = 76 ) . The HHP is a school-based physical activity program focusing on promoting a healthy lifestyle . It lasted for 8 months , and measurements were taken at the beginning and end of the program . Physiological variables ( total cholesterol , triglycerides , blood glucose , blood pressure , and maximal oxygen consumption ) , anthropometric variables ( body mass index ( BMI ) ) and behavioral variables ( breakfast , quality of diet , meal frequency , physical activity , sedentary behavior , sleep , and perceived health ) were evaluated . Repeated- measures ANOVA showed significant improvements ( p < 0.05 ) after the intervention for the intervention group in triglycerides , blood glucose and maximal oxygen consumption . Significant improvements were also observed in breakfast habits and quality of diet . Finally , a significant improvement in prevalence of normal levels was observed for total cholesterol , blood pressure , and BMI . It can therefore be stated that the HHP is an innovative and useful school-based program that can help to improve diet and health in childhood Background : To investigate whether changing the play environment in primary schools to one that includes greater risk and challenge increases physical activity and reduces body mass index ( BMI ) .Subjects/ Methods : A 2-year cluster r and omised controlled trial was undertaken in 16 New Zeal and schools ( years 1–8 ) . Intervention schools ( n=8 ) re design ed their play environments to encourage imaginative and independent free play by increasing opportunities for risk and challenge ( for example , rough- and -tumble play ) , reducing rules and adding new playground components ( for example , loose parts ) . Control schools ( n=8 ) were asked to not change their play environment . A qualified playworker rated all school play environments at baseline and 1 year . Primary outcomes were moderate-to-vigorous physical activity ( 7-day accelerometry ) and BMI z-score , collected in 840 children at baseline , 1 and 2 years . Data were analysed using generalised estimating equations . Results : Multiple changes were made to the school play environments result ing in a significant difference in overall play evaluation score between intervention and control schools of 4.50 ( 95 % confidence interval : 1.82 to 7.18 , P=0.005 ) , which represents a substantial improvement from baseline values of 19.0 ( s.d . 3.2 ) . Overall , schools liked the intervention and reported many benefits , including increased physical activity . However , these beliefs did not translate into significant differences in objective ly measured physical activity , either as counts per minute ( for example , 35 ( −51 to 120 ) during lunch break ) or as minutes of moderate-to-vigorous physical activity ( 0.4 , −1.1 to 2.0 ) . Similarly , no significant differences were observed for BMI , BMI z-score or waist circumference at 1 or 2 years ( all P>0.321 ) . Conclusions : Altering the school play environment to one that promoted greater risk and challenge for children did not increase physical activity , nor subsequently alter body weight . Although schools embraced the concept of adding risk and challenge in the playground , our findings suggest that children may have been involved in different , rather than additional activities BACKGROUND Childhood obesity is a major public health problem in the United States , particularly among American Indian communities . OBJECTIVE The objective was to evaluate the effectiveness of a school-based , multicomponent intervention for reducing percentage body fat in American Indian schoolchildren . DESIGN This study was a r and omized , controlled , school-based trial involving 1704 children in 41 schools and was conducted over 3 consecutive years , from 3rd to 5th grade s , in schools serving American Indian communities in Arizona , New Mexico , and South Dakota . The intervention had 4 components : 1 ) change in dietary intake , 2 ) increase in physical activity , 3 ) a classroom curriculum focused on healthy eating and lifestyle , and 4 ) a family-involvement program . The main outcome was percentage body fat ; other outcomes included dietary intake , physical activity , and knowledge , attitudes , and behaviors . RESULTS The intervention result ed in no significant reduction in percentage body fat . However , a significant reduction in the percentage of energy from fat was observed in the intervention schools . Total energy intake ( by 24-h dietary recall ) was significantly reduced in the intervention schools but energy intake ( by direct observation ) was not . Motion sensor data showed similar activity levels in both the intervention and control schools . Several components of knowledge , attitudes , and behaviors were also positively and significantly changed by the intervention . CONCLUSIONS These results document the feasibility of implementing a multicomponent program for obesity prevention in elementary schools serving American Indian communities . The program produced significant positive changes in fat intake and in food- and health-related knowledge and behaviors . More intense or longer interventions may be needed to significantly reduce adiposity in this population Background Adolescence is an established period of physical activity decline . Multi-component school-based interventions have the potential to slow the decline in adolescents ’ physical activity ; however , few interventions have been conducted in schools located in low-income or disadvantaged communities . This study aims to assess the effectiveness of a multi-component school-based intervention in reducing the decline in physical activity among students attending secondary schools located in disadvantaged communities . Methods / Design The cluster r and omised trial will be conducted with 10 secondary schools located in selected regions of New South Wales , Australia . The schools will be selected from areas that have a level of socio-economic status that is below the state average . Five schools will be allocated to receive an intervention based on the Health Promoting Schools framework , and will be supported by a part-time physical activity consultant placed in intervention schools who will implement a range of intervention adoption strategies . Study measures will be taken at baseline when students are in Year 7 ( 12–13 Output:	Conclusions School-based interventions are generally effective in reducing excessive weight gain of children .
MS2944	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background : A subset of patients with chronic obstructive pulmonary disease ( COPD ) may respond more favorably to inhaled corticosteroids ( ICS ) , but no simple method is currently utilized to predict the presence or absence of ICS responses in patients with COPD . We evaluated the ability of exhaled nitric oxide ( FENO ) and serum inflammatory markers ( C-reactive protein [ CRP ] , interleukin-6 [ IL-6 ] , and interleukin-8 [ IL-8 ] ) to independently predict spirometric responses to ICS in patients with COPD . Methods : Among 60 ex-smokers with severe COPD ( mean FEV1 1.07 L , 36 % of predicted ) , we conducted a single-arm , open-label study . Participants spent four weeks free of any ICS , followed by four weeks of ICS use ( fluticasone propionate 500 mcg twice daily ) . FENO , CRP , IL-6 , IL-8 , and pre-bronchodilator spirometry were measured immediately before and after the four weeks of ICS use . Results : Baseline FENO , CRP , IL-6 , and IL-8 showed no correlations to FEV1 responses to ICS . ICS responders ( increase in FEV1 ≥ 200 mL after four weeks of ICS ) did have significantly higher baseline FENO levels compared with non-responders ( 46.5 parts per billion [ ppb ] vs. 25 ppb , p = 0.028 ) . The receiver operating characteristic curve for FENO to discriminate responders from non-responders had an area under curve of 0.72 . Baseline serum inflammatory markers did not differ between responders and non-responders . Conclusion : In ex-smokers with severe COPD , a measure of local pulmonary inflammation , FENO , may be more closely associated with FEV1 responses to four weeks of ICS than are st and ard markers of systemic inflammation , serum CRP , IL-6 , and BACKGROUND The use of inhaled corticosteroids in mild to moderate COPD is controversial . The aim of this study was to determine whether airway hyperresponsiveness to mannitol might identify patients who are likely to respond to add-on inhaled corticosteroids . METHODS Ninety subjects with mild to moderate COPD were recruited and 68 subsequently r and omized in a double-blind manner to receive inhaled budesonide ( 1,600 μg/d , n = 31 ) or placebo ( n = 37 ) for 3 months . Thirty-eight subjects had airway hyperresponsiveness to mannitol ( 17 received budesonide , 21 placebo ) . All subjects received tiotropium throughout the study , including 4 weeks before r and omization . Spirometry , quality of life ( St. George Respiratory Question naire ) , degree of dyspnea , airway responsiveness to mannitol , and exhaled nitric oxide were assessed at week 0 ( recruitment ) , week 4 ( baseline prior to r and omization ) , and week 16 ( posttreatment ) . RESULTS Compared with placebo , budesonide was associated with improved quality of life in subjects showing airway hyperresponsiveness to mannitol ( difference of changes in quality of life score between r and omization and study completion , −9.1 ; 95 % CI , −15.8 to −2.3 ; P < .01 ) . Treatment with inhaled budesonide also led to a reduction in airway responsiveness to mannitol compared with placebo ( difference in log10 response-dose ratio , −0.3 ; 95 % CI , −0.6 to −0.04 ; P < .01 ) . However , postr and omization changes in FEV1 % predicted , quality of life , and exhaled nitric oxide showed no difference between budesonide and placebo . CONCLUSIONS In subjects with mild to moderate COPD and airway hyperresponsiveness to mannitol , quality of life and airway responsiveness improved after treatment with inhaled corticosteroids added to long-acting bronchodilator therapy BACKGROUND The exhaled nitric oxide ( FeNO ) is a non-invasive marker of airway inflammation in asthma . A very recent statement has suggested FeNO as potential outcome in chronic obstructive pulmonary disease ( COPD ) . Recently , a new h and -held FeNO analyzer ( NIOX MINO ) has been developed . PATIENTS AND METHODS We have evaluated the NIOX MINO in COPD patients and monitored FeNO levels during 1-year assessment in the outpatient setting . Short-term variability in FeNO was compared using a NIOX MINO and a stationary chemiluminescence analyzer ( NOA , Sensormedics ) in healthy volunteers and COPD patients on two consecutive months . Long-term FeNO variability was assessed on a cohort of 70 COPD out patients measuring FeNO for 1 year . The intra-individual FeNO coefficient of variation ( eNOCoV ) was taken as index FeNO long-term variability . RESULTS In COPD there were no significant differences between NIOX MINO and NOA FeNO values recorded at baseline and 1 month later . Ninety five percent limits of agreement between NIOX MINO and NOA were-2.7 and 1.9ppb with significant reliability ( r=0.96 , p<0.0001 ) . Mean FeNO at baseline was 15.0+/-9.5ppb . Over the 1-year period the overall mean FeNO was 15.5+/-10.1ppb . The long-term eNOCoV was 33.9+/-16.4 % ( range 8.1 - 83.1 % ) , and it was significantly associated with exacerbation rate ( r=0.57 , p<0.0001 ) . CONCLUSION FeNO electrochemical h and -held analyzer is feasible in COPD showing good agreement with stationary chemiluminescence analyzer . COPD patients exhibit a wide range of FeNO levels and a high variability of FeNO over time , which was positively associated with the number of exacerbations BACKGROUND Inhaled corticosteroids ( ICS ) treatment for asthma control is generally focused on lung function and symptoms , but inadequately correlated with airway inflammation . OBJECTIVE To compare asthma control in a group of patients whose treatment was based on fraction of exhaled nitric oxide ( FENO ) and sputum eosinophils ( intervention group ) with a group in whom treatment was based on clinical score ( control group ) . Study design and primary outcome : R and omized parallel-group longitudinal 24-month study including 5 visits every 6 months . A combination of asthma exacerbation rate and symptom score at 24 months was the primary outcome . PARTICIPANTS Fourteen patients with eosinophilic asthma per group were included . RESULTS In the intervention group , exacerbation rate/patient/year was reduced at 12 months ( 0.82 ) ( -73 % ) and , to a greater extent at 24 months ( 0.5 ) ( -84 % ) compared with baseline ( 3.21 , p<0.01 ) . In the control group , a significant reduction in exacerbation rate/patient/year was only observed between month 12 ( 3.0 ) and 24 ( 2.0 , -33 % , p<0.01 ) . At 24 months , exacerbation rate was lower ( -75 % ) in the intervention ( 0.5 ) than in the control group ( 2.0 , p<0.05 ) . Compared with baseline , mean symptom scores at 24 months were reduced in both groups ( intervention group : -72 % ; control group : - 60 % ) , but were lower in the intervention ( 8.1±1.0 , p<0.05 ; -27 % ) than in the control group ( 11±2.6 ) . ICS dose gradually increased in both groups throughout the study , with no between-group differences . CONCLUSION Compared with conventional strategy , longitudinal monitoring of FENO and sputum eosinophils improves eosinophilic asthma control in terms of reduced symptoms and exacerbations without additional increase e in ICS treatment RATIONALE Predicting corticosteroid response in COPD is important but difficult . Response is more likely to occur in association with eosinophilic airway inflammation , for which the fraction of exhaled nitric oxide ( Fe(NO ) ) is a good surrogate marker . OBJECTIVES We aim ed to establish whether Fe(NO ) levels would predict the clinical response to oral corticosteroid in COPD . METHODS We performed a double-blind , crossover trial of steroid in patients with COPD . After a 4-week washout of inhaled steroids , patients received prednisone 30 mg/d or matching placebo , in r and om order , with an intervening 4-week washout . The predictive values of Fe(NO ) for clinical ly significant changes in 6-minute-walk distance ( 6MWD ) , spirometry ( FEV(1 ) ) , and St. George 's Respiratory Question naire ( SGRQ ) were calculated . MEASUREMENTS AND MAIN RESULTS A total of 65 patients ( mean FEV(1 ) = 57 % predicted ) were r and omized . With prednisone , there was a net increase of 13 m in 6MWD ( P = 0.02 ) and 0.06 L in postbronchodilator FEV(1 ) ( P = 0.02 ) compared with placebo . The change in SGRQ was not significant . Using receiver operator characteristic analysis , the area under the curve for an increase of 0.2 L in FEV(1 ) was 0.69 ( P = 0.04 ) with an optimum Fe(NO ) cut-point of 50 ppb . The positive and negative predictive values were 67 and 82 % , respectively . FE(NO ) was not a significant predictor for changes in 6MWD or SGRQ . CONCLUSIONS Fe(NO ) is a weak predictor of short-term response to oral corticosteroid in COPD , its usefulness being limited to predicting increase in FEV(1 ) . Clinical trial registered with www.anzctr.org.au ( ACTRN12605000683639 ) The aim of the study was to evaluate the exhaled nitric oxide ( F(ENO ) ) in clinical ly stable chronic obstructive pulmonary disease ( COPD ) , its relationship to the severity of the disease , pulmonary function , smoking status , reversibility of airflow limitation , and ICS therapy . The study was conducted in 47 patients with COPD and 40 healthy controls . Flow/volume spirometry and F(ENO ) measurement were performed before and after 2 months of ICS therapy . F(ENO ) were significantly elevated in current smokers and ex-smoking COPD patients . In both groups of COPD patients inhaled corticosteroids ( ICS ) therapy caused a significant decrease in F(ENO ) without significant changes in FEV1 . A positive correlation between initial F(ENO ) and postbronchodilator FEV1 ( % predicted ) was observed in the group of ex-smoking COPD patients , but not in the currently smoking COPD group . In both groups of COPD patients , the initial level of F(ENO ) correlated with the reversibility of airway obstruction , the increase in postbronchodilator FEV1 and the decrease in F(ENO ) following ICS treatment . F(ENO ) increases in patients with stable COPD . ICS therapy decreased elevated F(ENO ) levels in these patients without statistically significant changes in lung function . The selection of COPD patients with increased F(ENO ) level and partial reversibility of airway obstruction should be helpful in terms of proposed ICS treatment There is controversy about the role of inhaled corticosteroids in chronic obstructive pulmonary disease ( COPD ) . Although they appear to have little impact on airways obstruction or its progression , their use may reduce the frequency and /or severity of exacerbations in a subset of patients . We undertook the following study to determine the impact of inhaled corticosteroid on two noninvasive markers of airways inflammation . We assigned 20 stable nonsmoking patients with COPD in r and om , double-blind crossover fashion to two 2-wk treatment periods with inhaled beclomethasone 500 microg twice daily or matching placebo , followed by a 2-wk washout period . We measured exhaled nitric oxide ( ENO ) , breath condensate H(2)O(2 ) , and flow volume spirometry at weekly intervals . Median baseline ENO was 26.2 ( 19.3 to 54.8 ) ppb and fell significantly following 1 and 2 wk of beclomethasone ( -10.6 ppb , p = 0.002 , and -6.3 ppb , p = 0.013 , respectively ) but was unchanged by placebo inhalation . Breath condensate H(2)O(2 ) levels did not change significantly with inhaled beclomethasone or placebo . Although there were no significant changes in FEV(1 ) with BDP therapy , there was a moderate inverse correlation between changes in ENO and changes in FEV(1 ) ( r -0.50 ) . We conclude that inhaled beclomethasone reduces ENO levels in stable nonsmoking patients with COPD , a finding compatible with an antiinflammatory mechanism of action The use of noninvasive methods of monitoring airway inflammation , such as exhaled nitric oxide ( eNO ) and induced sputum , has been shown to improve asthma monitoring and optimize treatment in adult patients with asthma . There is a lack of comparable data in children . Forty children Output:	Our findings indicate that FeNO levels significantly decreased with corticosteroid treatment in ex-smokers with COPD .
MS2945	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Type 2 diabetes accompanied by renal damage is a strong risk factor for atherosclerotic events . The purpose of this study was to investigate the efficacy of low-dose aspirin therapy on primary prevention of atherosclerotic events in patients with type 2 diabetes and coexisting renal dysfunction . RESEARCH DESIGN AND METHODS The Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes ( JPAD ) trial was a prospect i ve , r and omized , open-label trial conducted throughout Japan that enrolled 2,539 type 2 diabetic patients without a history of atherosclerotic diseases . Patients were assigned to the aspirin group ( 81 mg/day or 100 mg/day ) or the nonaspirin group and followed for a median of 4.37 years . The primary end points were atherosclerotic events of fatal and nonfatal ischemic heart disease , stroke , and peripheral arterial disease . RESULTS The analysis included 2,523 patients who had serum creatinine measured . In 1,373 patients with baseline estimated glomerular filtration rate ( eGFR ) 60–89 mL/min/1.73 m2 , the incidence of primary end points was significantly lower in the aspirin group than in the nonaspirin group ( aspirin , 30/661 ; nonaspirin , 55/712 ; hazard ratio 0.57 [ 95 % CI 0.36–0.88 ] ; P = 0.011 ) . Low-dose aspirin therapy did not reduce primary end points in patients with eGFR ≥90 mL/min/1.73 m2 ( aspirin , 9/248 ; nonaspirin , 11/270 ; 0.94 [ 0.38–2.3 ] ) or those with eGFR < 60 mL/min/1.73 m2 ( aspirin , 29/342 ; nonaspirin , 19/290 ; 1.3 [ 0.76–2.4 ] ) . The Cox proportional hazard model demonstrated a significant interaction between mild renal dysfunction ( eGFR 60–89 mL/min/1.73 m2 ) and aspirin ( P = 0.02 ) . CONCLUSIONS These results suggest a differential effect of low-dose aspirin therapy in diabetic patients with eGFR 60–89 mL/min/1.73 m2 Background —The role of glycoprotein IIb/IIIa receptor antagonists for the treatment of patients with acute coronary syndrome and renal insufficiency remains undefined . Methods and Results — Patients from the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms ( PRISM-PLUS ) trial were stratified by creatinine clearance ( CrCl ) and assessed with respect to treatment assignment to tirofiban/heparin versus heparin alone for the risk of adverse outcomes and bleeding . Patients with severe renal insufficiency ( defined as a serum creatinine ≥2.5 mg/dL ) were excluded from PRISM-PLUS as a whole . Patients with the lowest CrCl ( < 30 mL/min ) were more likely to present with high-risk clinical features . Decreasing renal function was strongly associated with adverse outcome , increasing the risk for ischemic complications at all time points examined ( all P < 0.002 ) . Irrespective of CrCl , therapy with tirofiban reduced the odds of the composite end point of death , myocardial infa rct ion , or refractory ischemia at 48 hours ( odds ratio [ OR ] , 0.68 ; 95 % confidence interval [ CI ] , 0.46 to 1.0;P = 0.05 ) , 7 days ( OR , 0.68 ; 95 % CI , 0.52 to 0.88;P = 0.003 ) , 30 days ( OR , 0.78 ; 95 % CI , 0.63 to 0.98;P = 0.03 ) , and 6 months ( OR , 0.81 ; 95 % CI , 0.68 to 0.98;P = 0.03 ) . The risk of myocardial infa rct ion/death was also significantly decreased to a similar magnitude at all time points examined . There was no evidence of treatment-by-CrCl interaction . The presence of declining renal function independently increased the risk for bleeding ( OR , 1.57;P < 0.001 for trend across categories ) , as did therapy with tirofiban , but no unexpected incremental risk of bleeding due to tirofiban was observed among lowest CrCl categories . Conclusions —Among patients with mild-to-moderate renal insufficiency in PRISM-PLUS , tirofiban was well tolerated and effective in reducing ischemic acute coronary syndrome complications Idiopathic membranoproliferative glomerulonephritis ( MPGN ) has a poor prognosis , with 90 % of patients requiring dialysis treatment after 20 years regardless of therapy . Up to 34 % of patients may die due to thrombotic complications or sepsis . This study investigates the influence of aspirin plus dipyridamole on proteinuria and renal function in nephrotic MPGN patients with moderately reduced glomerular filtration rate . Eighteen patients with biopsy-proven MPGN ( 15 type I , 3 type II ) and nephrotic syndrome were r and omly assigned to receive protein restriction , antihypertensive therapy ( control group ) or in addition aspirin and dipyridamole ( treatment group ) . Patients were prospect ively followed for a mean of 36 months . Serum creatinine remained unchanged after 36 months compared to baseline in both groups . In the treatment group proteinuria was reduced from 8.3 + /- 1.4 to 1.6 + /- 0.7 g/day ( P < 0.05 ) . In control patients proteinuria decreased from 7.1 + /- 1.6 to 4.3 + /- 1.1 g/day . After 36 months proteinuria was significantly lower in the treatment group compared to control ( P < 0.02 Mann-Whitney rank sum test ) . In conclusion , aspirin plus dipyridamole may be of value in reversing nephrotic syndrome and associated risks in patients with MPGN and moderately reduced renal function Since platelet cyclo-oxygenase is much more sensitive to inactivation by aspirin than is the enzyme in the arterial wall and low doses of aspirin may prevent thrombosis by blocking thromboxane synthesis , we conducted a r and omized , double-blind trial of aspirin ( 160 mg per day ) vs. placebo in 44 patients on chronic hemodialysis . The study was continued until there were 24 patients with thrombi and both groups had been under observation for a mean of nearly five months . Thrombi occurred in 18 of 25 ( 72 per cent ) of patients given placebo and 16 of 19 ( 32 per cent ) of those given aspirin ( P less than 0.01 ) . The incidence of thrombosis was reduced from 0.46 thrombi per patient month in the placebo group to 0.16 thrombi per patient month in the aspirin group ( p less than 0.005 ) . A dose of 160 mg of aspirin per day is an effective , nontoxic antithrombotic regimen in patients on hemodialysis Background — Reduced renal function is associated with a poorer prognosis and increased bleeding risk in patients with acute coronary syndromes and may therefore alter the risk-benefit ratio with antiplatelet therapies . In the Platelet Inhibition and Patient Outcomes ( PLATO ) trial , ticagrelor compared with clopidogrel reduced the primary composite end point of cardiovascular death , myocardial infa rct ion , and stroke at 12 months but with similar major bleeding rates . Methods and Results — Central laboratory serum creatinine levels were available in 15 202 ( 81.9 % ) acute coronary syndrome patients at baseline , and creatinine clearance , estimated by the Cockcroft Gault equation , was calculated . In patients with chronic kidney disease ( creatinine clearance < 60 mL/min ; n=3237 ) , ticagrelor versus clopidogrel significantly reduced the primary end point to 17.3 % from 22.0 % ( hazard ratio [ HR ] , 0.77 ; 95 % confidence interval [ CI ] , 0.65 to 0.90 ) with an absolute risk reduction greater than that of patients with normal renal function ( n=11 965 ) : 7.9 % versus 8.9 % ( HR , 0.90 ; 95 % CI , 0.79 to 1.02 ) . In patients with chronic kidney disease , ticagrelor reduced total mortality ( 10.0 % versus 14.0 % ; HR , 0.72 ; 95 % CI , 0.58 to 0.89 ) . Major bleeding rates , fatal bleedings , and non – coronary bypass – related major bleedings were not significantly different between the 2 r and omized groups ( 15.1 % versus 14.3 % ; HR , 1.07 ; 95 % CI , 0.88 to 1.30 ; 0.34 % versus 0.77 % ; HR , 0.48 ; 95 % CI , 0.15 to 1.54 ; and 8.5 % versus 7.3 % ; HR , 1.28 ; 95 % CI , 0.97 to 1.68 ) . The interactions between creatinine clearance and r and omized treatment on any of the outcome variables were nonsignificant . Conclusions — In acute coronary syndrome patients with chronic kidney disease , ticagrelor compared with clopidogrel significantly reduces ischemic end points and mortality without a significant increase in major bleeding but with numerically more non – procedure-related bleeding . Clinical Trial Registration — URL : http://www.clinicatrials.gov . Unique identifier : NCT00391872 When constructing arteriovenous fistulas for haemodialysis in chronic renal failure patients , one of the main problems is still their clotting tendency . Ticlopidine is an effective inhibitor of platelet aggregation . In this r and omized double-blind study placebo or ticlopidine 250 mg twice daily was given to chronic uremic patients up to 4 weeks after construction of an arteriovenous fistula . 42 patients were recruited and 36 completed the trial . The fistula clotted in 8 patients on placebo and in 2 patients on ticlopidine . The difference is significant . This effect was achieved without an increased frequency of side effects compared with placebo . It is concluded that ticlopidine has a function as a thromboprophylactic drug in chronic uremic patients The optimal vascular access for chronic maintenance hemodialysis is the arteriovenous fistula ( AVF ) . Several studies suggest a role for antiplatelet agents in the prevention of primary AVF failure . A double-blind , r and omized trial was conducted to assess the efficacy and safety of clopidogrel in hemodialysis patients . Ninety three patients were r and omized to receive 75 mg/daily of clopidogrel or placebo . The treatment was initiated 7–10 days prior to scheduled access surgery and continued up to six weeks postoperatively , and then patients were monitored for six months . The primary outcome was AVF failure eight weeks after fistula creation . With a permuted block r and omization schedule , 46 patients received clopidogrel and 47 patients received control placebo . The primary AVF failures at two months were 21.6 % in placebo group and 5.2 % in clopidogrel group ( P = 0.03 ) . The hazard ratio for the incidence of primary AVF failure was 0.72 ( CI 95 % , 0.41–1.01 ) . Analysis of covariables indicated that this effect occurred principally as a result of clopidogrel administration . First hemodialysis from newly created AVF in clopidogrel group was significantly more successful than placebo group ( P = 0.008 ) . No life-threatening adverse event or severe bleeding was recorded in both groups . Clopidogrel seems to be effective and safe for prevention of primary AVF failure in hemodialysis patients In a prospect i ve r and omized trial the anti-thrombotic effect of dipyridamole was studied in 64 patients after cadaveric kidney allotransplantation . The frequency of early graft function was significantly higher in the control group , whereas the incidence of arterial and venous thromboses were not different . One-year graft survival could not be improved by dipyridamole . Therefore , dipyridamole should not be recommended in cadaveric kidney allotransplantation BACKGROUND Mild and moderate chronic kidney disease ( CKD ) is associated with decreased survival and increased adverse events after a percutaneous coronary intervention ( PCI ) . Therapy with clopidogrel decreases adverse events in large patient population s. Therefore , we sought to determine the efficacy and safety of long-term clopidogrel therapy in patients with CKD . METHODS Two thous and two patients from the CREDO trial in whom an elective PCI of a single or multiple vessels was planned were analyzed . Patients were r and omly assigned to a 300-mg loading dose of clopidogrel before PCI followed by clopid Output:	Low- quality evidence has found that in persons with acute coronary syndromes , glycoprotein IIb/IIIa inhibitors or clopidogrel plus st and ard care compared with st and ard care alone had little or no effect on all-cause or cardiovascular mortality or on myocardial infa rct ion but increased serious bleeding . Benefits for antiplatelet therapy among persons with CKD are uncertain and are potentially outweighed by bleeding hazards .
MS2946	*TASK* the task is to summarize an input biomedical literature in six sentences *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 study was to evaluate the " Bike Smart " program , an eHealth software program that teaches bicycle safety behaviors to young children . METHODS Participants were 206 elementary students in grade s kindergarten to 3 . A r and om control design was employed to evaluate the program , with students assigned to either the treatment condition ( Bike Smart ) or the control condition ( a video on childhood safety ) . Outcome measures included computer-based knowledge items ( safety rules , helmet placement , hazard discrimination ) and a behavioral measure of helmet placement . RESULTS Results demonstrated that regardless of gender , cohort , and grade the participants in the treatment group showed greater gains than control participants in both the computer-presented knowledge items ( p > .01 ) and the observational helmet measure ( p > .05 ) . CONCLUSIONS Findings suggest that the Bike Smart program can be a low cost , effective component of safety training packages that include both skills-based and experiential training OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity Objective —To evaluate the effectiveness of a skills training program in improving safe cycling behavior , knowledge , and attitudes in young children . Methods — Grade 4 children from six elementary schools in East York ( a borough of Metropolitan Toronto ) participated . The intervention — playground based instruction on bicycle h and ling skills by certified instructors — was r and omly allocated to three schools . Altogether 141 children participated : 73 in the intervention group and 68 in the control group , with follow up evaluations available on 117 ( 83 % ) . The primary outcome was safe cycling behavior ( straight line riding , coming to a complete stop , and shoulder checking before a left turn ) . A self report question naire collected data on knowledge and attitudes . Baseline assessment s were made in June , with follow up evaluations in September , 1995 . Results —The prevalence of safe cycling behaviors at follow up in the intervention and control groups respectively , were : straight line riding ( 90 % v 88 % ; p=0.782 ) , coming to a complete stop ( 90 % v 76 % ; p=0.225 ) , and shoulder checking ( 0 % v 2 % ; p=1.000 ) . Over time ( from baseline to follow up ) children in both groups were more likely to maintain straight line riding , less likely to ride on the sidewalk , and less likely to consider that a car had more right to the road . Conclusions —This brief skills training program was not effective in improving safe cycling behavior , knowledge , or attitudes among grade 4 children Two training methods were developed to teach young cyclists ( 8/9 years ) how to behave in priority situations . One method was developed along the lines of the modelling principle . In earlier studies it was shown that this method is effective in teaching crossing strategies to young pedestrians . The other training method was based upon And erson 's Adaptive Control of Thought ( ACT ) theory , which describes the development of cognitive skills by proceduralisation and composition of behaviour and knowledge elements into automatic behaviour sequences . Two groups of children were trained with one of these methods . A control group did not receive traffic-related training in that period . The effect of the training was assessed by a knowledge test and a behaviour test . The results showed that the partly theoretical ACT approach initially result ed in an increased level of knowledge , which was found to have disappeared after a month . The modelling approach did not affect the level of knowledge . Both approaches had an equally positive effect on simple behavioural strategies , such as signalling and visual search behaviour . Correct application of priority rules appeared to be very difficult to teach . There was no effect of the two training methods . It seemed that children apply informal rules rather than formal rules when dealing with other traffic . It is hypothesized that these informal rules should form the starting point for training activities , because formal rules do not fit into children 's cognitive framework of schemes , and therefore can not be stored and retrieved effectively Objectives —To evaluate possible benefits of a school based bicycle safety education program ( “ Bike Ed ” ) on the risk of bicycle injury in children . Methods —A population based case-control study was undertaken in a region of Melbourne , Australia . Cases were children presenting at hospital emergency departments with injuries received while riding bicycles . Controls were recruited by calling r and omly selected telephone numbers . Data were collected by personal interview . Results — Analysis , based on 148 cases and 130 controls aged 9 to 14 years , showed no evidence of a protective effect and suggested a possible harmful effect of exposure to the bicycle safety course ( odds ratio ( OR ) 1.64 , 95 % confidence interval ( CI ) 0.98 to 2.75 ) . This association was not substantially altered by adjustment for sex , age , socioeconomic status , and exposure , measured as time or distance travelled . Subgroup analysis indicated that the association was strongest in boys ( OR 2.0 , 95 % CI 1.1 to 3.8 ) , younger children , children from families with lower parental education levels , and children lacking other family members who bicycle . Conclusions —It is concluded that this educational intervention does not reduce the risk of bicycle injury in children and may possibly produce harmful effects in some children , perhaps due to inadvertent encouragement of risk taking or of bicycling with inadequate supervision Output:	Overall , there was no statistically significant intervention effect on measures of injury . There is a paucity of high- quality research in the area of bicycle skills training programmes . Educational and skills training bicycling programmes may increase knowledge of cycling safety , but this does not seem to translate into a decrease in injury rate , or improved bicycle h and ling ability and attitudes
MS2947	*TASK* the task is to summarize an input biomedical literature in six sentences *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 mineral trioxide aggregate ( MTA ) with calcium hydroxide ( Ca(OH)2 ) clinical ly and radiographically as a pulpotomy agent in immature permanent teeth ( apexogenesis ) . METHODS Fifteen children , each with at least 2 immature permanent teeth requiring pulpotomy ( apexogenesis ) , were selected for this study . All selected teeth were evenly divided into 2 test groups . In group 1 , the conventional Ca(OH)2pulpotomy ( control ) was performed , whereas in group 2 , the MTA pulpotomy ( experimental ) was done . The children were recalled for clinical and radiographic evaluations after 3 , 6 , and 12 months . RESULTS The follow-up evaluations revealed failure due to pain and swelling detected at 6 and 12 months postoperative evaluations in only 2 teeth treated with Ca(OH)2 . The remaining 28 teeth appeared to be clinical ly and radiographically successful 12 months postoperatively . Calcific metamorphosis was a radiographic finding in 2 teeth treated with Ca(OH)2 and 4 teeth treated with MTA . CONCLUSIONS Mineral trioxide aggregate showed clinical and radiographic success as a pulpotomy agent in immature permanent teeth ( apexogenesis ) and seems to be a suitable alternative to calcium hydroxide PURPOSE To evaluate the results of using mineral trioxide aggregate ( MTA ) in pulpotomy procedures in primary teeth . METHODS Seven patients were selected and a total of 20 molars and two canines were treated with pulpotomy procedures using MTA instead of formocresol . RESULTS After 6 months , 55 % of the molars and 100 % of the canines treated showed radiographic signs of dentin bridge formation . Also , 6 months after treatment , 60 % of the molars showed root canal calcification ( obliteration ) . Color change of the crown of the canines treated was noticeable . No clinical or radiographic signs of pathology was observed Purpose The aim of this study was to compare the effect of white mineral trioxide aggregate ( MTA ) to that of formocresol ( FC ) as pulp dressing agents in pulpotomised primary molars . Methods In this clinical trial study , 60 lower second primary molars of 46 children were treated by a conventional pulpotomy technique . The teeth were r and omly assigned to the MTA ( experimental ) and FC ( control ) groups by r and om numbered table . Following removal of the coronal pulp and haemostasis , the pulp stumps were covered with an MTA paste in the experimental group . In the control group , FC was placed with a cotton pellet over the pulp stumps . The teeth of both groups were restored with stainless steel crowns . Children arrived for clinical and radiographic follow-up evaluation after 6 , 12 and 24 months . Results The treated teeth in FC group ( n = 18 ) were clinical ly and radiographically successful after 24 months . The radiographic follow-up evaluation revealed one failure ( furcation involvement ) in 18 molars treated with MTA after 24 months . The treated teeth in MTA group were clinical ly successful 24 months postoperatively . Pulp canal obliteration was observed in one of the teeth treated with MTA and four of the teeth treated with FC . Conclusion MTA could be used as a safe medicament for pulpotomy in cariously exposed primary molars and could be a substitute for FC The objective of the present study was to test the hypothesis that the fracture strength of calcium hydroxide and mineral trioxide aggregate (MTA)-filled immature teeth decreased over time . Immature m and ibular incisors from sheep were extracted and the pulps were extirpated using an apical approach with a barbed broach , and the teeth were divided into three experimental groups . Group 1 : untreated teeth . Group 2 : the root canals were filled with calcium hydroxide paste . Group 3 : the root canals were filled with MTA . All specimens were kept in saline with 1 % antibiotics at 4 degrees C for certain periods of time : 2 weeks , 2 months , and 1 year . Then they were tested for fracture strength in an Instron testing machine . The results were subjected to statistical analysis by the Tukey-Kramer tests . A P-value ( < 0.05 ) was considered statistically significant . One tooth from each group was selected r and omly for a histological study , examining matrix metalloproteinases ( MMP2 and MMP14 ) and tissue inhibitor of metalloproteinase ( TIMP ) . The results showed the mean fracture strengths decreased over time for all the three groups . Although the untreated teeth showed the highest value ( 45.5 MPa ) at 2 weeks , the fracture strengths decreased significantly after 2 months ( P < 0.05 ) . On the other h and , the teeth treated with calcium hydroxide or MTA decreased , but not significantly over time ( P > 0.05 ) . For the MTA-treated teeth , the fracture strengths were not found significantly different from the untreated or calcium hydroxide-treated teeth at 2 weeks or 2 months ( P > 0.05 ) . However , the strength was significantly higher in the MTA group compared with the other two groups after 1 year ( P < 0.05 ) . Immunofluorescence images revealed expression of collagen type 1 , MMP-2 and MMP-14 in both untreated and endodontically treated teeth . However , TIMP-2 was only observed in the MTA-treated teeth . In conclusion , the teeth with root treatment with MTA showed the highest fracture resistance at 1 year ( P < 0.05 ) . An explanation could be that MTA induced the expression of TIMP-2 in the dentin matrix and thereby possibly prevented destruction of the collagen matrix The purpose of this study was to compare the ability of different thicknesses of mineral trioxide aggregate ( MTA ) to prevent apical leakage through the use of a protein-dye complex with Coomassie Brilliant Blue G. Sixty-four teeth were divided into 4 groups , then filled with MTA to depths of 1 , 2 , 3 , or 4 mm . Two teeth served as the positive controls . Another 2 teeth served as the negative controls . Root-filled teeth were mounted in an apparatus and then challenged with protein solution . The evaluation was conduced at 24-hour intervals for 60 days . The 1-mm-thick MTA was the least effective in preventing apical leakage ( P < .05 ) . No significance difference was found between 2- and 3-mm-thick MTA ( P > .05 ) . Four-millimeter-thick MTA was significantly more effective than the other thicknesses tested ( P < .05 ) . The results of this study suggest that the thickness of 4 mm is most adequate for the use of MTA as a root-end filling material PURPOSE The objective of this study was to assess the effect of mineral trioxide aggregate ( MTA ) as pulp dressing material following pulpotomy in primary molars with carious pulp exposure and compare them to those of formocresol ( FC ) . METHODS Of 33 children , primary molars treated via a conventional pulpotomy technique were r and omly assigned to the MTA group ( 33 teeth ) or FC group ( 29 teeth ) . Clinical and radiographic follow-up ranged between 4 and 74 months . The mean follow-up time was 38 months , with no difference between the groups . Twenty-nine teeth were followed until uneventful shedding ( mean=33 months ) . Failures were detected after a mean period of 16 months ( range=4 to 30 ) . RESULTS The success rate of pulpotomy was 97 % for MTA ( 1 failure ) and 83 % for FC ( 5 failures ) . Eight teeth presented internal resorption . In 4 of them ( 2 of each group ) , progress of the resorption process stopped and the pulp tissue was replaced by a radioopaque calcified tissue . Pulp canal obliteration was observed in 58 % of the MTA group and in 52 % of the FC group ( total=55 % ) . CONCLUSIONS MTA showed a higher ( though not statistically significant ) long-term clinical and radiographic success rate than formocresol , and can be recommended as its replacement as , unlike FC , MTA does not induce undesirable responses The purpose of the study was to compare several methods that have been used to assess marginal leakage of root canal fillings . Sixty-three extracted , single-rooted teeth were instrumented and filled in a st and ardized manner . Teeth were r and omly divided into groups of twenty and exposed to solutions containing methylene blue dye , calcium-45 , carbon-14-labeled urea , and iodine-125-labeled albumin for 48 hours to compare the degree of leakage indicated by each technique . Methylene blue dye was found to penetrate farther up the canal than any of the isotope tracers . Carbon-14-labeled urea penetrated farther than the calcium-45- or iodine-125-labeled albumin . The mean volume of solution penetrating the teeth was exceedingly small ( 0.0011 ml ) and probably unimportant physiologically PURPOSE To evaluate the clinical , radiographical and histological findings in human third molars in which mechanical pulp exposures were capped with white ProRoot mineral trioxide aggregate ( WMTA ) . METHODS Forty-eight human third molars , caries-free or with incipient caries , scheduled to be extracted , were used and r and omly divided into two groups : Group A : ( n= 24 ) received WMTA and control Group B : ( n= 24 ) received chemical set calcium hydroxide ( Dycal ) . The teeth were isolated with rubber dam and Class I cavities prepared . Pulp exposure was performed using a sterile diamond bur and confirmed by frank bleeding . A sterile cotton pellet dipped in saline solution was placed over the exposure for 60 seconds . The preparation was then lightly rinsed with water and gently air-dried . WMTA or CH was placed over the exposure site followed by a small amount of a light-cured compomer . After etching with 35 % phosphoric acid gel for 15 seconds , rinsing and blot drying , Prime and Bond NT adhesive was applied and light-cured . The cavity was then restored with a resin composite and light-cured . Evaluations were performed by phone after 7 days and clinical ly at 30 + /- 5 and 136 + /- 24 days , using st and ardized tests and radiographs . The teeth were extracted after 136 + /- 24 days ; the roots were cut + /- 4 - 5 mm from the apex to allow for rapid fixation in 10 % neutral buffered formalin . They were then processed for routine histological evaluation , embedded in paraffin , sectioned and stained with hematoxylin and eosin and Brown and Brenn for recognition of bacteria . Statistical analyses were performed using a Mann-Whitney U-test , a Chi-square test , a Fisher 's exact test and an ANOVA . RESULTS No significant differences in post-operative sensitivity were reported after 7 days between the two material s ( P > 0.05 ) . Clinical examination demonstrated no significant differences at 30 + /- 5 days ( P > 0.05 ) and at 136 + /- 24 days ( P > 0.05 ) . Histological findings : 45 of 48 teeth were suitable for microscopic evaluation ( 22 with WMTA and 23 with CH ) . Twenty from the WMTA and 18 from the CH group had developed a bridge . No statistically significant differences were found for superficial and deep inflammatory cell response ( P > 0.05 ) , presence of a dentin bridge ( P > 0.01 ) , and pulp vitality ( P > 0.01 ) , between WMTA and calcium hydroxide . A statistically significant difference was found for the diameter of exposure ( P < or = 0.05 ) between WMTA ( x= 0.35 + /- 0.19 mm ) and CH ( x= 0.25 + /- 0.09 mm ) . Only a minimal association between clinical and histological findings could be established for either material After 2 yrs ' follow-up , mineral trioxide aggregate ( MTA ) appeared suitable for this purpose AIM To compare the outcome after 6 months of the application of formocresol ( FC ) or mineral trioxide aggregate ( MTA ) during pulpotomy in primary molar teeth . METHODOLOGY A maximum of 126 children ( aged 5 - 9 years ) with carious primary teeth that required pulpotomy were selected . Following r and omization , a st and ard pulpotomy preparation was undertaken , and the coronal pulp removed and bleeding arrested . In the FC group , cotton balls , soaked in FC , were placed for 5 min , and then the pulp chamber was filled with Zonalin , a pulpotomy agent . In the MTA group , a 1-mm-thick paste of MTA was used as a pulpotomy agent . The crowns in both groups were restored with amalgam or glass ionomer . The teeth of 100 patients were evaluated and compared clinical ly and radiographically after 3 and 6 months . RESULTS No signs of clinical failure were observed at the 3- and 6-month follow-up appointments in either group . There were no significant differences in the radiographic findings of the teeth and surrounding tissue at the 3-month follow-up . However , at the 6-month follow-up , significantly more cases ( P = 0.036 ) with root resorption were seen in the FC group ; no cases of resorption occurred amongst the MTA cases . The surrounding tissue showed radiographic signs of post-treatment disease in four FC cases ; none was seen in the MTA cases . CONCLUSION After 6 months , pulpotomy with MTA was associated with fewer cases of root resorption and post-treatment disease . MTA appears to be a reliable alternative material for pulpotomy in primary molar teeth PURPOSE The aim of this study was to compare the effect of mineral trioxide aggregate ( MTA ) to that of formocresol ( FC ) Output:	Clinical impressions have generally been favourable and support the findings of laboratory and animal-based investigations .
MS2948	*TASK* the task is to summarize an input biomedical literature in six sentences *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 examine the relationship of urinary incontinence ( UI ) and depressive symptoms ( DS ) in older adults . DESIGN A r and omized , controlled trial to determine the effects of clinical practice guideline implementation on provider attitudes and behavior , and patients ' UI , health status , quality of life , and satisfaction with care . Baseline and endpoint data were collected from patients via computer-assisted telephone interviewing . SETTING Forty-one nonacademic primary care practice s ( PCP ) in North Carolina . PARTICIPANTS A total of 668 community-dwelling adults ( age > 60 ) who had visited the one of the selected PCPs . INTERVENTION PCPs in the intervention group were given instruction in the detection and management of UI , educational material s for providers and patients , office system supports , and academic detailing . MEASUREMENTS The dependent measure was assessed using an eight-item screener for DS . UI ( status , frequency , amount ) , health ( physical , mental ) , and demographic ( age , gender , marital status ) and self-report information about bladder control served as predictors . RESULTS Wilcoxon rank sum tests showed that UI status was associated with moderate to severe DS ( 43 % vs 30 % , P = .05 ) . Multivariate analyses showed that UI status , physical and mental health , and gender were significant predictors of DS . Among UI adults ( n = 230 ) , physical and mental health , life satisfaction , and the perception that UI interfered with daily life were significant predictors of DS . CONCLUSIONS This study provides clear evidence that UI is related to DS in older adults PURPOSE Initial weight loss improves urinary incontinence in overweight and obese women . In this study we examined the longer term effects of a weight loss intervention on urinary incontinence . MATERIAL S AND METHODS Overweight and obese women ( mean + /- SD age 53 + /- 10 years ) with 10 or more urinary incontinence episodes weekly were r and omized to an 18-month behavioral weight loss intervention ( 226 ) or control group ( 112 ) . Outcome measures were collected at 12 and 18 months . RESULTS At baseline women had a mean body mass index of 36 + /- 6 kg/m(2 ) and reported a mean of 24 + /- 18 incontinence episodes weekly . Of the patients 86 % completed 18-month measurements . The percent weight loss in the intervention group averaged 8.0 % , 7.5 % and 5.5 % at 6 , 12 and 18 months , respectively , vs approximately 1.5 % in the control group ( all values p < 0.001 ) . Compared with controls at 12 months the intervention group reported a greater percent reduction in weekly stress urinary incontinence episodes ( 65 % vs 47 % , p < 0.001 ) , and a greater proportion achieved at least a 70 % decrease in weekly total and stress urinary incontinence episodes . At 18 months a greater proportion of women in the weight loss intervention group had more than 70 % improvement in urge incontinence episodes but there were no significant differences between the groups for stress or total urinary incontinence . The intervention group also reported greater satisfaction with changes in urinary incontinence than the control group at 6 , 12 and 18 months . CONCLUSIONS Weight loss intervention reduced the frequency of stress incontinence episodes through 12 months and improved patient satisfaction with changes in incontinence through 18 months . Improving weight loss maintenance may provide longer term benefits for urinary incontinence OBJECTIVES To determine whether a multifaceted intervention based on the Agency for Health Care Policy and Research ( AHCPR ) Clinical Practice Guidelines for Urinary Incontinence would increase primary care physician screening for and management of urinary incontinence ( UI ) . DESIGN Group r and omized trial , conducted from 1996 to 1997 . SETTING Internal medicine and family medicine community practice s. PARTICIPANTS Forty-one primary care practice s , including 57 physicians and their staff and 1,145 patients aged 60 and older . INTERVENTION Twenty of the 41 primary care practice s in North Carolina were r and omized to a composite intervention that included a 3-hour continuing medical education accredited course , training in management of UI , patient educational material s , and on-site physician and office support . The remaining 21 practice s served as " usual care " controls . Telephone surveys of UI status and quality of life were obtained from 1,145 patients before the intervention . At 1 year , patients and physicians were contacted by telephone and mail to determine the effect of the educational intervention . MEASUREMENTS Patients completed telephone surveys to assess screening for UI , UI status , treatment interventions , and quality of life . Physicians completed surveys related to UI treatment and practice patterns . RESULTS Baseline and endpoint telephone surveys were completed by 668 of 1,145 ( 58 % ) of patients , who were cared for by 45 physicians ( 10 internists , 35 family medicine ) . Physician screening rates for UI were 22 % for those patients who did not report UI . UI was reported by 39.5 % of patients at baseline , of whom 30 % reported being asked about UI by their primary care physician during the study . Rates of assessment and management of existing UI were low in both the control and intervention groups . Additional historical question ing indicated that 54.2 % reported that they had ever undergone assessment , including history , urinalysis , or testing , or had had management of their UI by any physician . CONCLUSION Attempts at increasing screening and management of UI by primary care physicians using the AHCPR st and ardized guidelines using a multifaceted system of educational and logistical support were not successful . These guidelines may not be the best approach to treating UI in the primary care setting OBJECTIVES To report on the responsiveness testing and clinical utility of the 12-item Geriatric Self-Efficacy Index for Urinary Incontinence ( GSE-UI ) . DESIGN Prospect i ve cohort study . SETTING Six urinary incontinence ( UI ) outpatient clinics in Quebec , Canada . PARTICIPANTS Community-dwelling incontinent adults aged 65 and older . MEASUREMENTS The abridged 12-item GSE-UI , measuring older adults ' level of confidence for preventing urine loss , was administered to all new consecutive incontinent patients 1 week before their initial clinic visit , at baseline , and 3 months posttreatment . At follow-up , a positive rating of improvement in UI was ascertained from patients and their physicians using the Patient 's and Clinician 's Global Impression of Improvement scales , respectively . Responsiveness of the GSE-UI was calculated using Guyatt 's change index . Its clinical utility was determined using receiver operating curves . RESULTS Eighty-nine of 228 eligible patients ( 39.0 % ) participated ( mean age 72.6 + 5.8 , range 65 - 90 ) . At 3-month follow-up , 22.5 % of patients were very much better , and 41.6 % were a little or much better . Guyatt 's change index was 2.6 for patients who changed by a clinical ly meaningful amount and 1.5 for patients having experienced any level of improvement . An improvement of 14 points on the 12-item GSE-UI had a sensitivity of 75.1 % and a specificity of 78.2 % for detecting clinical ly meaningful changes in UI status . Mean GSE-UI scores varied according to improvement status ( P<.001 ) and correlated with changes in quality -of-life scores ( r=0.7 , P<.001 ) and reductions in UI episodes ( r=0.4 , P=.004 ) . CONCLUSION The GSE-UI is responsive and clinical ly useful OBJECTIVES To assess whether urinary incontinence ( UI ) and its severity are associated with poor self-rated health in a national sample of community-living older adults and whether this relationship persists after controlling for confounding attributable to functional status , comorbidity , and demographic factors . DESIGN A cross-sectional analysis using multivariate logistic regression . SETTING Subjects were from the 1990 - 1991 National Survey of Self-Care and Aging ( N = 3485 ) , a r and om sampling in geographic clusters of community-dwelling Medicare beneficiaries 65 years of age or older in the contiguous United States . MEASURES The responses to an interviewer-administered question naire regarding urinary incontinence , Basic Activities of Daily Living ( BADL ) , Instrumental Activities of Daily Living ( IADL ) , Mobility Activities of Daily Living ( MADL ) , age , gender , place of residence , race , education , need for proxy response to the survey , and number of medical conditions . RESULTS Unadjusted analysis showed the presence of urinary incontinence to be associated with poor self-rated health ( OR 2.7 , 2.1 - 3.3 ) . With gender , number of comorbid conditions , race , IADL impairment , and interaction terms of incontinence/race and incontinence/IADL in the final model , UI was associated with poor self-rated health in certain subgroups . White subjects with no IADL impairment and mild-moderate incontinence had an OR of 2.0 ( 95 % CI 1.5 - 2.9 ) and those with severe incontinence had an OR of 4.5 ( 95 % CI 2.4 - 8.4 ) of rating their health as poor , whereas those with no IADL impairment and no incontinence were the referent group . For those with a lot of difficulty performing one or more IADL activity , the association of UI and poor self-rated health was weak . For non-white subjects , there was no association , or a very weak association , of UI and poor self-rated health . CONCLUSION In this national sample , urinary incontinence was independently and positively associated with poor self-rated health after adjustment for age , comorbidity , and frailty for most community-dwelling older adults . This association between UI and poor self-rated health was weaker and statistically insignificant when IADL impairment was present or in non-white subjects . Further research is indicated to better underst and the impact of urinary incontinence in specific cultural setting BACKGROUND AND PURPOSE The effects of a home exercise program for persons with chronic peripheral neuropathies ( CPN ) have not been documented . We compared changes in impairment and health-related quality of life ( HRQL ) between exercise and control groups , investigated the relationship between HRQL and measures of impairment , and contrasted the HRQL of individuals with CPN to that previously described for the general population . SUBJECTS Twenty-eight subjects with CPN , aged 23 to 84 years ( mean = 56.2 , SD = 14.9 ) , completed the study . METHODS Impairment measures included average muscle score ( AMS ) , h and grip force , walking time , and forced vital capacity . The HRQL instrument measured the eight scales of the Medical Outcomes Study 36-Item Short-Form Health Survey ( SF-36 ) and the component scales . The exercise group ( n = 14 ) completed a 6-week home exercise program . The control group ( n = 14 ) did not participate in a home exercise program . RESULTS There was an increase in the AMS in the exercise group compared with the control group . No other between-group differences were found . The exercise group improved in scores on the role limitation scales of the SF-36 . The AMS and walking time were moderately correlated with the physical function scale of the SF-36 ( r = .55 and -.62 , respectively ) . The SF-36 scores of individuals with CPN were lower than scores previously described for the general population . CONCLUSION AND DISCUSSION The home exercise program appears to be an important component of the treatment of persons with CPN . Compared with the general population , patients with CPN appear to have a lower HRQL , but some areas appear to improve following a home exercise program OBJECTIVE Diabetes is associated with increased urinary incontinence risk . Weight loss improves incontinence , but exercise may worsen this condition . We examined whether an intensive lifestyle intervention or metformin therapy among overweight pre-diabetic women was associated with a lower prevalence of incontinence . RESEARCH DESIGN AND METHODS We analyzed data from the Diabetes Prevention Program , a r and omized controlled trial in 27 U.S. centers . Of the 1,957 women included in this analysis , 660 ( 34 % ) were r and omized to intensive lifestyle therapy , 636 ( 32 % ) to metformin , and 661 ( 34 % ) to placebo with st and ard lifestyle advice . The main outcome measure was incontinence symptoms by frequency and type by a vali date d question naire completed at the end-of-trial visit ( mean 2.9 years ) . RESULTS The prevalence of total ( stress or urge ) weekly incontinence was lower among women in the intensive lifestyle group ( 38.3 % ) than those r and omized to metformin ( 48.1 % ) or placebo ( 45.7 % ) . This difference was most apparent among women with stress incontinence ( 31.3 % for intensive lifestyle group vs. 39.7 % for metformin vs. 36.7 % for placebo , P = 0.006 ) . Changes in weight accounted for most of the protective effect of the intensive lifestyle intervention on stress incontinence . CONCLUSIONS Less-frequent urinary incontinence may be a powerful motivator for women to choose lifestyle modification to prevent diabetes AIMS Few studies have documented the effectiveness of continence promotion programs targeting older in Output:	Women reported significant improvement in self-efficacy and incontinence-related quality of life .
MS2949	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Painful oral mucositis is a common complication after bone marrow transplantation ( BMT ) . Glutamine is a nutrient for rapidly dividing cells and the major energy source for intestinal epithelium . This study tested whether an oral glutamine preparation could decrease the severity of oral mucositis in patients undergoing BMT . Glutamine or a placebo ( glycine ) were administered from admission until day + 28 in 193 BMT patients in a r and omized , double-blind , placebo-controlled study at a dose of 1.0 g amino acid/m2/dose swish and swallow four times a day . In autologous BMT patients ( n = 87 ) glutamine was associated with significantly less mouth pain by self report and by opiate use ( 5.0 ± 6.2 days of morphine for glutamine vs 10.3 ± 9.8 days for placebo ; P = 0.005 ) . Matched sibling BMT patients had no effect by self report and an increased duration of opiate use ( 23.2 ± 5.7 days for glutamine vs 16.3 ± 8.3 days for placebo ) ( P = 0.002 ) . However , day 28 survival of allogeneic patients was improved by glutamine . No significant differences in TPN use , rate of relapse or progression of malignancy , parenteral antibiotic use , acute or chronic GVHD , or days of hospitalization were observed in either autologous or allogeneic recipients . No toxicity of glutamine was observed . We conclude that oral glutamine can decrease the severity and duration of oropharyngeal mucositis in autologous BMT patients but not in allogeneic BMT patients , possibly due to interaction with methotrexate Based on the assumption that an accelerated proliferation process prevails in tumour cell residues after surgery , the possibility that treatment acceleration would offer a therapeutic advantage in postoperative radiotherapy of locally advanced head and neck cancer was investigated . The value of Tpot in predicting the treatment outcome and in selecting patients for accelerated fractionation was tested . Seventy patients with ( T2/N1–N2 ) or ( T3 - 4/any N ) squamous cell carcinoma of the oral cavity , larynx and hypopharynx who underwent radical surgery , were r and omized to either ( a ) accelerated hyperfractionation : 46.2 Gy per 12 days , 1.4 Gy per fraction , three fractions per day with 6 h interfraction interval , treating 6 days per week or ( b ) Conventional fractionation : 60 Gy per 6 weeks , 2 Gy per fraction , treating 5 days per week . The 3-year locoregional control rate was significantly better in the accelerated hyperfractionation ( 88±4 % ) than in the CF ( 57±9 % ) group , P=0.01 ( and this was confirmed by multivariate analysis ) , but the difference in survival ( 60±10 % vs 46±9 % ) was not significant ( P=0.29 ) . The favourable influence of a short treatment time was further substantiated by demonstrating the importance of the gap between surgery and radiotherapy and the overall treatment time between surgery and end of radiotherapy . Early mucositis progressed more rapidly and was more severe in the accelerated hyperfractionation group ; reflecting a faster rate of dose accumulation . Xerostomia was experienced by all patients with a tendency to be more severe after accelerated hyperfractionation . Fibrosis and oedema also tended to be more frequent after accelerated hyperfractionation and probably represent consequential reactions . Tpot showed a correlation with disease-free survival in a univariate analysis but did not prove to be an independent factor . Moreover , the use of the minimum and corrected P-values did not identify a significant cut-off . Compared to conventional fractionation , accelerated hyperfractionation did not seem to offer a survival advantage in fast tumours though a better local control rate was noted . This limits the use of Tpot as a guide for selecting patients for accelerated hyperfractionation . For slowly growing tumours , tumour control and survival probabilities were not significantly different in the conventional fractionation and accelerated hyperfractionation groups . A rapid tumour growth was associated with a higher risk of distant metastases ( P=0.01 ) . In conclusion , tumour cell re population seems to be an important determinant of postoperative radiotherapy of locally advanced head and neck cancer despite lack of a definite association between Tpot and treatment outcome . In fast growing tumours accelerated hyperfractionation provided an improved local control but without a survival advantage . To gain a full benefit from treatment acceleration , the surgery-radiotherapy gap and the overall treatment time should not exceed 6 and 10 weeks respectively The aim of this study was to see if antibiotic pastilles could reduce radiation mucositis , pain , dysphagia and weight loss in patients undergoing radical radiotherapy for head and neck cancer . A total of 275 patients with T1-T4 tumours entered the study ; 136 were allocated to suck four times daily a pastille containing amphotericin , polymyxin and tobramycin . The remaining 139 patients received an identical placebo . In all , 54 patients were unevaluable ( 24 active , 30 placebo ) . Bacteriological monitoring was carried out before and twice weekly during treatment . Both arms of the study were well balanced for T and N stage , age , sex and radiation dose ( 60 Gy ) . There was a slight imbalance in the site of disease which had no substantive effect on the results . The primary study end point was the percentage of patients who developed intermediate or thick pseudomembranes . No statistically significant difference was found in this end point , with 36 % of patients in the active arm developing this type of membrane compared with 48 % in the placebo arm ( P = 0.118 ) . The estimated odds ratio ( placebo/active ) of developing an intermediate or thick pseudomembrane was 1.59 ( 95 % CI 0.89 - 2.82 ) . However a more sensitive test comparing the worst recorded mucositis grade between the two arms was statistically significant ( P = 0.009 ) . This indicated that the active pastilles had a beneficial effect , but the magnitude was probably smaller than the trial was design ed to detect . There was a reduction in mucositis distribution ( P = 0.002 ) , mucositis area ( P = 0.028 ) , dysphagia ( P = 0.006 ) and weight loss ( P = 0.009 ) in the active arm . There was a clear tendency for patients with positive cultures for aerobic Gram-negative bacteria ( AGNB ) ( P = 0.003 ) and yeasts ( P = 0.026 ) during treatment to have more severe mucositis . The active pastilles reduced the percentage of patients with yeast cultures ( P = 0.003 ) but had less effect on AGNB . The benefit derived from the pastilles should material ly increase patient tolerance to radical radiotherapy for head and neck cancer Background . Oral mucositis is a common complication of bone marrow transplantation ( BMT ) conditioning therapy . Sequelae consist of increased risk for infection , moderate to severe pain , compromised oral function , and bleeding . This study investigated helium‐neon laser treatment for prevention of conditioning‐induced oral mucositis in BMT patients . Patterns and severity of mucositis for specific conditioning drug regimens also were analyzed PURPOSE In a single-institution , double-blind , prospect i ve , r and omized trial , we determined whether oral aloe vera gel can reduce radiation-induced mucositis in head- and -neck cancer patients . METHODS AND MATERIAL S We r and omized 58 head- and -neck cancer patients between oral aloe vera and placebo . To be included in this Phase II protocol , patients had to be treated with radiotherapy with curative intent at Stanford University between February 1999 and March 2002 . We examined patients biweekly for mucositis at 15 head- and -neck subsites and administered quality -of-life question naires . RESULTS Patients in the aloe and placebo groups were statistically identical in baseline characteristics . By the end of treatment , the two groups were also statistically identical in maximal grade of toxicity , duration of Grade 2 or worse mucositis , quality -of-life scores , percentage of weight loss , use of pain medications , hydration requirement , oral infections , and prolonged radiation breaks . CONCLUSION In our r and omized study , oral aloe vera was not a beneficial adjunct to head- and -neck radiotherapy . The mean quality -of-life scores were greater in the aloe vera group , but the differences were not statistically significant . Oral aloe vera did not improve tolerance to head- and -neck radiotherapy , decrease mucositis , reduce soreness , or otherwise improve patient well-being BACKGROUND Oral mucositis is a complication of intensive chemotherapy and radiotherapy with no effective treatment . We tested the ability of palifermin ( recombinant human keratinocyte growth factor ) to decrease oral mucosal injury induced by cytotoxic therapy . METHODS This double-blind study compared the effect of palifermin with that of a placebo on the development of oral mucositis in 212 patients with hematologic cancers ; 106 patients received palifermin ( 60 microg per kilogram of body weight per day ) and 106 received a placebo intravenously for three consecutive days immediately before the initiation of conditioning therapy ( fractionated total-body irradiation plus high-dose chemotherapy ) and after autologous hematopoietic stem-cell transplantation . Oral mucositis was evaluated daily for 28 days after transplantation . RESULTS The incidence of oral mucositis of World Health Organization ( WHO ) grade 3 or 4 was 63 percent in the palifermin group and 98 percent in the placebo group ( P<0.001 ) . Among patients with this degree of mucositis , the median duration of mucositis was 6 days ( range , 1 to 22 ) in the palifermin group and 9 days ( range , 1 to 27 ) in the placebo group . Among all patients , regardless of the occurrence of mucositis , the median duration of oral mucositis of WHO grade 3 or 4 was 3 days ( range , 0 to 22 ) in the palifermin group and 9 days ( range , 0 to 27 ) in the placebo group ( P<0.001 ) . As compared with placebo , palifermin was associated with significant reductions in the incidence of grade 4 oral mucositis ( 20 percent vs. 62 percent , P<0.001 ) , patient-reported soreness of the mouth and throat ( area-under-the-curve score , 29.0 [ range , 0 to 98 ] vs. 46.8 [ range , 0 to 110 ] ; P<0.001 ) , the use of opioid analgesics ( median , 212 mg of morphine equivalents [ range , 0 to 9418 ] vs. 535 mg of morphine equivalents [ range , 0 to 9418 ] , P<0.001 ) , and the incidence of use of total parenteral nutrition ( 31 percent vs. 55 percent , P<0.001 ) . Adverse events , mainly rash , pruritus , erythema , mouth and tongue disorders , and taste alteration , were mild to moderate in severity and were transient . CONCLUSIONS Palifermin reduced the duration and severity of oral mucositis after intensive chemotherapy and radiotherapy for hematologic cancers PURPOSE Experimental and clinical data suggest a reduction of radiation-induced acute toxicity by amifostine . We investigated this issue in a r and omized trial comparing radiochemotherapy ( RCT ) versus radiochemotherapy and amifostine ( RCT + A ) in patients with head and neck cancer . PATIENTS AND METHODS Forty-seven patients with pharyngeal or laryngeal cancer ( T1 - 2 N1 - 2 G3 , T3 - 4 N0 - 2 G1 - 3 ) were r and omized to receive RCT alone ( 21 patients ) or RCT + A ( 21 patients ) . Patients were irradiated up to 60 Gy ( R0 ) or 70 Gy ( R1/2 ) . Chemotherapy consisted of 70 mg/m2 carboplatin and was administered over 5 days in the 1st and 5th week of the radiotherapy course . 250 mg amifostine were applied daily just before each radiotherapy session . Acute toxicity was evaluated according to the Common Toxicity Criteria ( CTC ) . As for xerostomia no patients with laryngeal cancer were assessed because in these cases only small volumes of the salivary gl and s were within the treatment volume . To evaluate the overall toxicity a summarized CTC score of all observed side effects was calculated . RESULTS Forty-two patients were evaluable . Clinical characteristics ( age , sex , Karnofsky index , tumor-staging ) were well balanced in both treatment groups ( Tables 2 and 3 ) . Amifostine provided reduction in xerostomia and mucositis ( Figures 5 and 6 ) but had no obvious influence on Karnofsky index , body weight , cutaneous side effects and alopecia ( Figures 1 to 4 ) . CONCLUSIONS According to our preliminary results amifostine has a radioprotective effect on salivary gl and s. Mucositis can be reduced during radiochemotherapy . At this point of patient accrual the difference between both groups are statistically not significant . To improve the radioprotective effects of amifostine in clinical practice the application of a Output:	Ten interventions were found to have some benefit with regard to preventing or reducing the severity of mucositis associated with cancer treatment .
MS2950	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Several polymorphisms in DNA repair genes have been reported to be associated with lung cancer risk including XPA ( -4G/A ) , XPD ( Lys751Gln and Asp312Asn ) , XRCC1 ( Arg399Gln ) , APE1 ( Asp148Glu ) and XRCC3 ( Thr241Met ) . As there is little information on the combined effects of these variants , polymorphisms were analyzed in a case-control study including 463 lung cancer cases [ among them 204 adenocarcinoma and 212 squamous cell carcinoma ( SCC ) ] and 460 tumor-free hospital controls . Odds ratios ( OR ) adjusted for age , gender , smoking and occupational exposure were calculated for the variants alone and combinations thereof . For homozygous individuals carrying the Glu variant of APE1 , a protective effect was found ( OR = 0.77 , CI = 0.51 - 1.16 ) . Individuals homozygous for the variants XPA ( -4A ) ( OR = 1.53 , CI = 0.94 - 2.5 ) , XPD 751Gln ( OR = 1.39 , CI = 0.90 - 2.14 ) or XRCC3 241Met ( OR = 1.29 , CI = 0.85 - 1.98 ) showed a slightly higher risk for lung cancer overall . In the subgroup of adenocarcinoma cases , adjusted ORs were increased for individuals homozygous for XPA ( -4A ) ( OR = 1.62 , CI = 0.91 - 2.88 ) and XRCC3 241Met ( OR = 1.65 ; CI = 0.99 - 2.75 ) . When analyzing the combined effects of variant alleles , 54 patients and controls were identified that were homozygous for two or three of the potential risk alleles [ i.e. the variants in nucleotide excision repair , XPA ( -4A ) and XPD 751Gln , and in homologous recombination , XRCC3 - 241Met ] . ORs were significantly increased when all patients ( OR = 2.37 ; CI = 1.26 - 4.48 ) , patients with SCC ( OR = 2.83 ; CI = 1.17 - 6.85 ) and with adenocarcinoma ( OR = 3.05 ; CI = 1.49 - 6.23 ) were analyzed . Combinations of polymorphisms in genes involved in the same repair pathway ( XPA + XPD or XRCC1 + APE1 ) affected lung cancer risk only in patients with SCC . These results indicate that lung cancer risk is only moderately increased by single DNA repair gene variants investigated but it is considerably enhanced by specific combinations of variant alleles . Analyses of additional DNA repair gene interactions in larger population -based studies are warranted for identification of high-risk subjects Several single nucleotide polymorphisms ( SNPs ) affecting DNA repair capacity and modifying cancer susceptibility have been described . We evaluated the association of SNPs Arg194Trp , Arg280His , and Arg399Gln in the X-ray cross-complementing group 1 ( XRCC1 ) and Thr241Met in the X-ray cross-complementing group 3 ( XRCC3 ) DNA repair genes with the risk of brain tumors . The Caucasian study population consisted of 701 glioma ( including 320 glioblastoma ) cases , 524 meningioma cases , and 1,560 controls in a prospect i ve population -based case – control study conducted in Denmark , Finl and , Sweden , and the UK . The studied SNPs were not significantly associated with the risk of brain tumors . The highest odds ratios ( ORs ) for the associations were observed between the homozygous variant genotype XRCC1 Gln399Gln and the risk of glioma ( OR = 1.32 ; 95 % confidence interval , CI , 0.97–1.81 ) , glioblastoma ( OR = 1.48 ; 95 % CI , 0.98–2.24 ) , and meningioma ( OR = 1.34 ; 95 % CI , 0.96–1.86 ) . However , in pair-wise comparisons a few SNP combinations were associated with the risk of brain tumors : Among others , carriers of both homozygous variant genotypes , i.e. , XRCC1 Gln399Gln and XRCC3 Met241Met , were associated with a three-fold increased risk of glioma ( OR = 3.18 ; 95 % CI , 1.26–8.04 ) and meningioma ( OR = 2.99 ; 95 % CI , 1.16–7.72 ) . In conclusion , no significant association with brain tumors was found for any of the polymorphisms , when examined one by one . Our results indicated possible associations between combinations of XRCC1 and XRCC3 SNPs and the risk of brain tumors Environmental carcinogens contained in air pollution , such as polycyclic aromatic hydrocarbons , aromatic amines or N-nitroso compounds , predominantly form DNA adducts but can also generate interstr and cross-links and reactive oxygen species . If unrepaired , such lesions increase the risk of somatic mutations and cancer . Our study investigated the relationships between 22 polymorphisms ( and their haplotypes ) in 16 DNA repair genes belonging to different repair pathways in 1094 controls and 567 cancer cases ( bladder cancer , 131 ; lung cancer , 134 ; oral-pharyngeal cancer , 41 ; laryngeal cancer , 47 ; leukaemia , 179 ; death from emphysema and chronic obstructive pulmonary disease , 84 ) . The design was a case-control study nested within a prospect i ve investigation . Among the many comparisons , few polymorphisms were associated with the diseases at the univariate analysis : XRCC1 - 399 Gln/Gln variant homozygotes [ odds ratios ( OR ) = 2.20 , 95 % confidence intervals ( CI ) = 1.16 - 4.17 ] and XRCC3 - 241 Met/Met homozygotes ( OR = 0.51 , 95 % CI = 0.27 - 0.96 ) and leukaemia . The recessive model in the stepwise multivariate analysis revealed a possible protective effect of XRCC1 - 399Gln/Gln in lung cancer ( OR = 0.22 , 95 % CI = 0.05 - 0.98 ) , and confirmed an opposite effect ( OR = 2.47 , 95 % CI = 1.02 - 6.02 ) in the leukaemia group . Our results also suggest that the XPD/ERCC1-GAT haplotype may modulate leukaemia ( OR = 1.28 , 95 % CI = 1.02 - 1.61 ) , bladder cancer ( OR = 1.38 , 95 % CI = 1.06 - 1.79 ) and possibly other cancer risks . Further investigations of the combined effects of polymorphisms within these DNA repair genes , smoking and other risk factors may help to clarify the influence of genetic variation in the carcinogenic process Output:	Many of the reported SNPs had diverse association with specific human cancers . For example , there was a positive association between the OGG1 Ser326Cys variant and gastric and lung cancer , while the XRCC1 Arg399Gln variant was associated with reduced cancer risk .
MS2951	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Sclerosis ( MS ) is a demyelinating autoimmune disease that imposes a significant emotional burden with heavy psychosocial consequences . Several studies have investigated the association between MS and mental disorders such as depression and anxiety , and recently research ers have focused also on Post-traumatic Stress Disorder ( PTSD ) . This is the first study that investigates the usefulness of proposing a treatment for PTSD to patients with MS . Methods : A r and omized controlled trial with patients with MS diagnosed with PTSD comparing Eye Movement Desensitization and Reprocessing ( EMDR ; n = 20 ) and Relaxation Therapy ( RT ; n = 22 ) . The primary outcome measure was the proportion of participants that no longer meet PTSD diagnosis as measured with Clinician Administered PTSD Scale 6-months after the treatment . Results : The majority of patients were able to overcome their PTSD diagnosis after only 10 therapy sessions . EMDR treatment appears to be more effective than RT in reducing the proportion of patients with MS suffering from PTSD . Both treatments are effective in reducing PTSD severity , anxiety and depression symptoms , and to improve Quality of Life . Conclusion : Although our results can only be considered preliminary , this study suggests that it is essential that PTSD symptoms are detected and that brief and cost-effective interventions to reduce PTSD and associated psychological symptoms are offered to patients , in order to help them to reduce the psychological burden associated with their neurological condition . Trial registration : NCT01743664 , https:// clinical BACKGROUND More than a third of the approximately 10 million women with histories of interpersonal violence in the United States develop posttraumatic stress disorder ( PTSD ) . Currently available treatments for this population have a high rate of incomplete response , in part because problems in affect and impulse regulation are major obstacles to resolving PTSD . This study explored the efficacy of yoga to increase affect tolerance and to decrease PTSD symptomatology . METHOD Sixty-four women with chronic , treatment-resistant PTSD were r and omly assigned to either trauma-informed yoga or supportive women 's health education , each as a weekly 1-hour class for 10 weeks . Assessment s were conducted at pretreatment , midtreatment , and posttreatment and included measures of DSM-IV PTSD , affect regulation , and depression . The study ran from 2008 through 2011 . RESULTS The primary outcome measure was the Clinician-Administered PTSD Scale ( CAPS ) . At the end of the study , 16 of 31 participants ( 52 % ) in the yoga group no longer met criteria for PTSD compared to 6 of 29 ( 21 % ) in the control group ( n = 60 , χ²₁ = 6.17 , P = .013 ) . Both groups exhibited significant decreases on the CAPS , with the decrease falling in the large effect size range for the yoga group ( d = 1.07 ) and the medium to large effect size decrease for the control group ( d = 0.66 ) . Both the yoga ( b = -9.21 , t = -2.34 , P = .02 , d = -0.37 ) and control ( b = -22.12 , t = -3.39 , P = .001 , d = -0.54 ) groups exhibited significant decreases from pretreatment to the midtreatment assessment . However , a significant group × quadratic trend interaction ( d = -0.34 ) showed that the pattern of change in Davidson Trauma Scale significantly differed across groups . The yoga group exhibited a significant medium effect size linear ( d = -0.52 ) trend . In contrast , the control group exhibited only a significant medium effect size quadratic trend ( d = 0.46 ) but did not exhibit a significant linear trend ( d = -0.29 ) . Thus , both groups exhibited significant decreases in PTSD symptoms during the first half of treatment , but these improvements were maintained in the yoga group , while the control group relapsed after its initial improvement . DISCUSSION Yoga significantly reduced PTSD symptomatology , with effect sizes comparable to well- research ed psychotherapeutic and psychopharmacologic approaches . Yoga may improve the functioning of traumatized individuals by helping them to tolerate physical and sensory experiences associated with fear and helplessness and to increase emotional awareness and affect tolerance . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00839813 Background A large proportion of mindfulness-based therapy trials report statistically significant results , even in the context of very low statistical power . The objective of the present study was to characterize the reporting of “ positive ” results in r and omized controlled trials of mindfulness-based therapy . We also assessed mindfulness-based therapy trial registration s for indications of possible reporting bias and review ed recent systematic review s and meta-analyses to determine whether reporting biases were identified . Methods CINAHL , Cochrane CENTRAL , EMBASE , ISI , MEDLINE , PsycInfo , and SCOPUS data bases were search ed for r and omized controlled trials of mindfulness-based therapy . The number of positive trials was described and compared to the number that might be expected if mindfulness-based therapy were similarly effective compared to individual therapy for depression . Trial registries were search ed for mindfulness-based therapy registration s. CINAHL , Cochrane CENTRAL , EMBASE , ISI , MEDLINE , PsycInfo , and SCOPUS were also search ed for mindfulness-based therapy systematic review s and meta-analyses . Results 108 ( 87 % ) of 124 published trials reported ≥1 positive outcome in the abstract , and 109 ( 88 % ) concluded that mindfulness-based therapy was effective , 1.6 times greater than the expected number of positive trials based on effect size d = 0.55 ( expected number positive trials = 65.7 ) . Of 21 trial registration s , 13 ( 62 % ) remained unpublished 30 months post-trial completion . No trial registration s adequately specified a single primary outcome measure with time of assessment . None of 36 systematic review s and meta-analyses concluded that effect estimates were overestimated due to reporting biases . Conclusions The proportion of mindfulness-based therapy trials with statistically significant results may overstate what would occur in practice Posttraumatic stress disorder ( PTSD ) is a debilitating condition that affects approximately 10 % of women in the United States . Although effective psychotherapeutic treatments for PTSD exist , clients with PTSD report additional benefits of complementary and alternative approaches such as yoga . In particular , yoga may downregulate the stress response and positively impact PTSD and comorbid depression and anxiety symptoms . We conducted a pilot study of a r and omized controlled trial comparing a 12-session Kripalu-based yoga intervention with an assessment control group . Participants included 38 women with current full or subthreshold PTSD symptoms . During the intervention , yoga participants showed decreases in reexperiencing and hyperarousal symptoms . The assessment control group , however , showed decreases in reexperiencing and anxiety symptoms as well , which may be a result of the positive effect of self-monitoring on PTSD and associated symptoms . Between-groups effect sizes were small to moderate ( 0.08 - 0.31 ) . Although more research is needed , yoga may be an effective adjunctive treatment for PTSD . Participants responded positively to the intervention , suggesting that it was tolerable for this sample . Findings underscore the need for future research investigating mechanisms by which yoga may impact mental health symptoms , gender comparisons , and the long-term effects of yoga practice Yoga may be effective in the reduction of PTSD symptomology . The purpose of this study was to evaluate the impact of a Kundalini Yoga ( KY ) treatment on PTSD symptoms and overall wellbeing . To supplement the current field of inquiry , a pilot r and omized control trial ( RCT ) was conducted comparing an 8-session KY intervention with a waitlist control group . 80 individuals with current PTSD symptoms participated . Both groups demonstrated changes in PTSD symptomology but yoga participants showed greater changes in measures of sleep , positive affect , perceived stress , anxiety , stress , and resilience . Between-groups effect sizes were small to moderate ( 0.09–0.25 ) . KY may be an adjunctive or alternative intervention for PTSD . Findings indicate the need for further yoga research to better underst and the mechanism of yoga in relation to mental and physical health , gender and ethnic comparisons , and short- and long-term yoga practice for psychiatric conditions BACKGROUND Posttraumatic stress disorder ( PTSD ) is prevalent among military veterans and is associated with significant negative health outcomes . However , stigma and other barriers to care prevent many veterans from pursuing traditional mental health treatment . We developed a group-based Integrative Exercise ( IE ) program combining aerobic and resistance exercise , which is familiar to veterans , with mindfulness-based practice s suited to veterans with PTSD . This study aim ed to evaluate the effects of IE on PTSD symptom severity and quality of life , as well as assess the feasibility and acceptability of IE . METHODS Veterans ( N = 47 ) were r and omized to either IE or waitlist control ( WL ) . Veterans in IE were asked to attend three 1-h group exercise sessions for 12 weeks . RESULTS Compared with WL , veterans r and omized to IE demonstrated a greater reduction in PTSD symptom severity ( d = -.90 ) , a greater improvement in psychological quality of life ( d = .53 ) and a smaller relative improvement in physical quality of life ( d = .30 ) Veterans ' ratings of IE indicated high feasibility and acceptability . LIMITATIONS The sample was relatively small and recruited from one site . The comparison condition was an inactive control . CONCLUSIONS This initial study suggests that IE is an innovative approach to treating veterans with symptoms of PTSD that reduces symptoms of posttraumatic stress and improves psychological quality of life . This approach to recovery may exp and the reach of PTSD treatment into non-traditional setting s and to veterans who may prefer a familiar activity , such as exercise , over medication or psychotherapy OBJECTIVE This study 's objective was to evaluate the effect of two common components of meditation ( mindfulness and slow breathing ) on potential mechanistic pathways . METHODS A total of 102 combat veterans with posttraumatic stress disorder ( PTSD ) were r and omized to ( a ) the body scan mindfulness meditation ( MM ) , ( b ) slow breathing ( SB ) with a biofeedback device , ( c ) mindful awareness of the breath with an intention to slow the breath ( MM+SB ) , or ( d ) sitting quietly ( SQ ) . Participants had 6 weekly one-on-one sessions with 20 minutes of daily home practice . The mechanistic pathways and measures were as follows : ( a ) autonomic nervous system ( hyperarousal symptoms , heart rate [ HR ] , and heart rate variability [ HRV ] ) ; ( b ) frontal cortex activity ( attentional network task [ ANT ] conflict effect and event-related negativity and intrusive thoughts ) ; and ( c ) hypothalamic-pituitary-adrenal axis ( awakening cortisol ) . PTSD measures were also evaluated . RESULTS Meditation participants had significant but modest within-group improvement in PTSD and related symptoms , although there were no effects between groups . Perceived impression of PTSD symptom improvement was greater in the meditation arms compared with controls . Resting respiration decreased in the meditation arms compared with SQ . For the mechanistic pathways , ( a ) subjective hyperarousal symptoms improved within-group ( but not between groups ) for MM , MM+SB , and SQ , while HR and HRV did not ; ( b ) intrusive thoughts decreased in MM compared with MM+SB and SB , while the ANT measures did not change ; and ( c ) MM had lower awakening cortisol within-group ( but not between groups ) . CONCLUSION Treatment effects were mostly specific to self-report rather than physiological measures . Continued research is needed to further evaluate mindfulness meditation 's mechanism in people with PTSD This preliminary study examined whether the practice of mind – body techniques decreases symptoms of posttraumatic stress in adolescents . Posttraumatic Stress Reaction Index question naires were collected from 139 high school students in Kosovo who participated in a 6-week program that included meditation , biofeedback , drawings , autogenic training , guided imagery , genograms , movement , and breathing techniques . Three separate programs were held approximately 2 months apart . There was no control group . Posttraumatic stress scores significantly decreased after participation in the programs . These scores remained decreased in the 2 groups that participated in the follow-up study when compared to pretest measures . These data indicate that mind – body skills groups were effective in reducing posttraumatic stress symptoms in war-traumatized high school students OBJECTIVES This r and omized controlled trial of yoga for military veterans and active duty personnel with posttraumatic stress disorder ( PTSD ) evaluated the efficacy of a 10-week yoga intervention on PTSD . METHOD Fifty-one participants were r and omized into yoga or no-treatment assessment -only control groups . Primary outcome measures included question naires and the Clinician Administered PTSD Scale . RESULTS Both yoga ( n = 9 ) and control ( n = 6 ) participants showed significant decreases in reexperiencing symptoms , with no significant between-group differences . Secondary within-group analyses of a self-selected wait-list yoga group ( n = 7 ) showed significant reductions in PTSD symptoms after yoga participation , in contrast to their control group participation . Consistent with current literature regarding high rates of PTSD treatment dropout for veterans , this study faced challenges retaining participants across conditions . CONCLUSION These results are consistent with recent literature indicating that yoga may have potential Output:	In most of the nine mindfulness and six yoga studies , significant between-group effects were found indicating moderate to large effect size advantages for these treatments .
MS2952	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Trastuzumab , a monoclonal antibody against human epidermal growth factor receptor 2 ( HER2 ; also known as ERBB2 ) , was investigated in combination with chemotherapy for first-line treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer . METHODS ToGA ( Trastuzumab for Gastric Cancer ) was an open-label , international , phase 3 , r and omised controlled trial undertaken in 122 centres in 24 countries . Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumours showed overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation . Participants were r and omly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine plus cisplatin or fluorouracil plus cisplatin given every 3 weeks for six cycles or chemotherapy in combination with intravenous trastuzumab . Allocation was by block r and omisation stratified by Eastern Cooperative Oncology Group performance status , chemotherapy regimen , extent of disease , primary cancer site , and measurability of disease , implemented with a central interactive voice recognition system . The primary endpoint was overall survival in all r and omised patients who received study medication at least once . This trial is registered with Clinical Trials.gov , number NCT01041404 . FINDINGS 594 patients were r and omly assigned to study treatment ( trastuzumab plus chemotherapy , n=298 ; chemotherapy alone , n=296 ) , of whom 584 were included in the primary analysis ( n=294 ; n=290 ) . Median follow-up was 18.6 months ( IQR 11 - 25 ) in the trastuzumab plus chemotherapy group and 17.1 months ( 9 - 25 ) in the chemotherapy alone group . Median overall survival was 13.8 months ( 95 % CI 12 - 16 ) in those assigned to trastuzumab plus chemotherapy compared with 11.1 months ( 10 - 13 ) in those assigned to chemotherapy alone ( hazard ratio 0.74 ; 95 % CI 0.60 - 0.91 ; p=0.0046 ) . The most common adverse events in both groups were nausea ( trastuzumab plus chemotherapy , 197 [ 67 % ] vs chemotherapy alone , 184 [ 63 % ] ) , vomiting ( 147 [ 50 % ] vs 134 [ 46 % ] ) , and neutropenia ( 157 [ 53 % ] vs 165 [ 57 % ] ) . Rates of overall grade 3 or 4 adverse events ( 201 [ 68 % ] vs 198 [ 68 % ] ) and cardiac adverse events ( 17 [ 6 % ] vs 18 [ 6 % ] ) did not differ between groups . INTERPRETATION Trastuzumab in combination with chemotherapy can be considered as a new st and ard option for patients with HER2-positive advanced gastric or gastro-oesophageal junction cancer . FUNDING F Hoffmann-La Roche The optimal adjuvant treatment for gastric cancer remains controversial . We compared the efficacy of a docetaxel and platinum adjuvant chemotherapy regimen , in patients with high-risk gastric cancer , with that of the same chemotherapy plus radiation therapy ( RT ) . In addition , we evaluated the prognostic and /or predictive value of a panel of molecular markers . Patients with histologically proven , radically resected gastric cancer , stage ≥T3 and /or N+ were r and omized to 6 cycles of docetaxel with cisplatin , both at 75 mg/m2 every 3 weeks ( arm A ) or the same treatment with RT ( arm B ; 45 Gy ) . Due to excessive nausea and vomiting , cisplatin was substituted by carboplatin at AUC ( area under the curve ) of 5 after the first 45 patients ( 22 group A , 23 group B ) . The prognostic value of EGFR , ERCC1 , HER2 , MET/HGFR , MAP-Tau , and PTEN expression was also studied in a subset of 67 patients using immunohistochemistry on tissue microarrays ( TMAs ) . A total of 147 patients were r and omized . After a median follow-up of 53.7 months , no differences in overall ( OS ) and disease-free survival ( DFS ) were found between the two arms . The most common grade 3/4 toxicities for arms A and B ( excluding alopecia ) were non-febrile neutropenia ( 11 and 17 % , respectively ) , febrile neutropenia ( 9 and 7 % ) and diarrhea ( 7 and 4 % , respectively ) . Patients with ERCC1 positive tumors had significantly longer median DFS ( 33.1 vs. 11.8 months , Wald P = 0.016 ) and OS ( 63.2 vs. 18.8 months , Wald P = 0.046 ) . Our results indicate that the addition of RT to platinum/docetaxel adjuvant chemotherapy does not appear to improve survival in high-risk , radically resected gastric cancer . However , the possibility that a benefit by the addition of RT was not detected due to decreased power of the study should not be excluded PURPOSE Amplification of the MET proto-oncogene in gastroesophageal cancer ( GEC ) may constitute a molecular marker for targeted therapy . We examined a GEC cohort with follow-up and reported the clinical response of four additional patients with MET-amplified tumors to the small molecule inhibitor crizotinib as part of an exp and ed phase I cohort study . PATIENTS AND METHODS From 2007 to 2009 , patients with GEC were genetically screened as a consecutive series of 489 tumors ( stages 0 , I , and II , 39 % ; III , 25 % ; IV , 36 % ; n = 222 esophageal , including n = 21 squamous carcinomas ) . MET , EGFR , and HER2 amplification status was assessed by using fluorescence in situ hybridization . RESULTS Ten ( 2 % ) of 489 patients screened harbored MET amplification ; 23 ( 4.7 % ) harbored EGFR amplification ; 45 ( 8.9 % ) harbored HER2 amplification ; and 411 ( 84 % ) were wild type for all three genes ( ie , negative ) . MET-amplified tumors were typically high- grade adenocarcinomas that presented at advanced stages ( 5 % ; n = 4 of 80 ) . EGFR-amplified tumors showed the highest fraction of squamous cell carcinoma ( 17 % ; n = 4 of 23 ) . HER2 , MET , and EGFR amplification were , with one exception ( MET and EGFR positive ) , mutually exclusive events . Survival analysis in patients with stages III and IV disease showed substantially shorter median survival in MET/EGFR-amplified groups , with a rank order for all groups by median survival ( from most to least aggressive ) : MET ( 7.1 months ; P < .001 ) less than EGFR ( 11.2 months ; P = .16 ) less than HER2 ( 16.9 months ; P = .89 ) when compared with the negative group ( 16.2 months ) . Two of four patients with MET-amplified tumors treated with crizotinib experienced tumor shrinkage ( -30 % and -16 % ) and experienced progression after 3.7 and 3.5 months . CONCLUSION MET amplification defines a small and aggressive subset of GEC with indications of transient sensitivity to the targeted MET inhibitor crizotinib ( PF-02341066 ) PURPOSE To investigate whether prognosis of patients with high-risk gastric cancer may depend on MET copy number gain ( CNG ) or an activating truncation within a deoxyadenosine tract element ( DATE ) in the promoter region of the MET lig and HGF . PATIENTS AND METHODS A single-institution cohort of 230 patients with stage II/III gastric cancer was studied . Formalin-fixed paraffin-embedded tumor specimens were used for DNA extraction . Quantitative polymerase chain reaction ( qPCR ) for MET CNG and sequencing for HGF DATE truncation ( < 25 deoxyadenosines instead of 30 ) were used . Results were analyzed for association with disease-free survival ( DFS ) and overall survival ( OS ) . To assess the reliability of the qPCR measurement , a r and om sample of cases was reanalyzed using an alternative assay ( fluorescent in situ hybridization [ FISH ] ) with calculation of the intracorrelation coefficient ( ICC ) . RESULTS In 216 assessable patients , MET CNG five or more copies and homozygous HGF-truncated DATE occurred in 21 patients ( 10 % ) and 30 patients ( 13 % ) , respectively . Patients with MET CNG five or more copies ( MET-positive ) showed significantly worse prognosis with multivariate hazard ratio ( HR ) of 3.02 ( 95 % CI , 1.71 to 5.33 ; P < .001 ) for DFS and multivariate HR of 2.91 ( 95 % CI , 1.65 to 5.11 ; P < .001 ) for OS . The agreement between qPCR and FISH was high , with ICC = 0.9 % ( 95 % CI , 0.81 % to 0.95 % ; the closer the ICC is to 1 , the greater is the agreement ) . HGF-truncated DATE did not show relevant prognostic effect . CONCLUSION In this study , qPCR revealed approximately 10 % of white patients with gastric cancer harboring MET CNG of five or more copies . This marker was significantly associated with unfavorable prognosis . This information is relevant to the current clinical development of anti-MET compounds Output:	The findings from present study indicated that higher MET gene amplification and expression in gastric cancer was an indicator of poor prognosis
MS2953	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background : Acute renal dysfunction ( ARD ) and subsequent acute renal failure after cardiac surgery are associated with high mortality and morbidity . Early therapeutic or preventive intervention is hampered by the lack of an early biomarker for acute renal injury . Recent studies showed that urinary neutrophil gelatinase – associated lipocalin ( NGAL or lipocalin 2 ) is up-regulated early ( within 1–3 h ) after murine renal injury and in pediatric ARD after cardiac surgery . The authors hypothesized that postoperative urinary NGAL concentrations are increased in adult patients developing ARD after cardiac surgery compared with patients without ARD . Methods : After institutional review board approval , 81 cardiac surgical patients were prospect ively studied . Urine sample s were collected immediately before incision and at various time intervals after surgery for NGAL analysis by quantitative immunoblotting . ARD was defined as peak postoperative serum creatinine increase by 50 % or greater compared with preoperative serum creatinine . Results : Sixteen of 81 patients ( 20 % ) developed postoperative ARD , and the mean urinary NGAL concentrations in patients who developed ARD were significantly higher early after surgery ( after 1 h : 4,195 ± 6,520 [ mean ± SD ] vs. 1,068 ± 2,129 ng/ml ; P < 0.01 ) compared with patients who did not develop ARD . Mean urinary NGAL concentrations continued to increase and remained significantly higher at 3 and 18 h after cardiac surgery in patients with ARD . In contrast , urinary NGAL in patients without ARD decreased rapidly after cardiac surgery . Conclusions : Patients developing postoperative ARD had significantly higher urinary NGAL concentrations early after cardiac surgery . Urinary NGAL may therefore be a useful early biomarker of ARD after cardiac surgery . These findings may facilitate the early detection of acute renal injury and potentially prevent progression to acute renal failure BACKGROUND AND OBJECTIVES The authors have previously shown that urine neutrophil gelatinase-associated lipocalin ( NGAL ) , measured by a research ELISA , is an early predictive biomarker of acute kidney injury ( AKI ) after cardiopulmonary bypass ( CPB ) . In this study , whether an NGAL immunoassay developed for a st and ardized clinical platform ( ARCHITECT analyzer , Abbott Diagnostics Division , Abbott Laboratories , Abbott Park , IL ) can predict AKI after CPB was tested . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS In a pilot study with 136 urine sample s ( NGAL range , 0.3 to 815 ng/ml ) and 6 calibration st and ards ( NGAL range , 0 to 1000 ng/ml ) , NGAL measurements by research ELISA and by the ARCHITECT assay were highly correlated ( r = 0.99 ) . In a subsequent study , 196 children undergoing CPB were prospect ively enrolled and serial urine NGAL measurements obtained by ARCHITECT assay . The primary outcome was AKI , defined as a > or = 50 % increase in serum creatinine . RESULTS AKI developed in 99 patients ( 51 % ) , but the diagnosis using serum creatinine was delayed by 2 to 3 d after CPB . In contrast , mean urine NGAL levels increased 15-fold within 2 h and by 25-fold at 4 and 6 h after CPB . For the 2-h urine NGAL measurement , the area under the curve was 0.95 , sensitivity was 0.82 , and the specificity was 0.90 for prediction of AKI using a cutoff value of 100 ng/ml . The 2-h urine NGAL levels correlated with severity and duration of AKI , length of stay , dialysis requirement , and death . CONCLUSIONS Accurate measurements of urine NGAL are obtained using the ARCHITECT platform . Urine NGAL is an early predictive biomarker of AKI severity after CPB Objective : To compare the value of novel with conventional serum biomarkers in the prediction of acute kidney injury ( AKI ) in adult cardiac surgical patients according to preoperative renal function . Design : Single-center , prospect i ve observational study . Setting : Tertiary hospital . Patients : One hundred adult cardiac surgical patients . Measurements and Main Results : We measured concentrations of plasma neutrophil gelatinase-associated lipocalin ( NGAL ) , and serum cystatin C , and creatinine and urea at baseline , on arrival in the intensive care unit ( ICU ) and at 24 hours postoperatively . We assessed such biomarkers in relation to the development of AKI ( > 50 % increase in creatinine from baseline ) and to a composite end point ( need for renal replacement therapy and in-hospital mortality ) . We defined an area under the receiver operating characteristic curve of 0.60–0.69 as poor , 0.70–0.79 as fair , 0.80–0.89 as good , and 0.90–1.00 as excellent in terms of predictive value . On arrival in ICU , plasma NGAL and serum cystatin C were of good predictive value , but creatinine and urea were of poor predictive value . After exclusion of patients with preoperative renal impairment ( estimated glomerular filtration rate < 60 mL/min ) , the predictive performance for AKI of all renal biomarkers on arrival in ICU remained unchanged except for cystatin C , which was of fair value in such patients . At 24 hours postoperatively , all renal biomarkers were of good predictive value . On arrival in ICU , novel biomarkers were superior to conventional biomarkers ( p < 0.05 ) . Plasma NGAL ( p = 0.015 ) and serum cystatin C ( p = 0.007 ) were independent predictors of AKI and of excellent value in the prediction of the composite end point . Conclusions : Early postoperative measurement of plasma NGAL was of good value in identifying patients who developed AKI after adult cardiac surgery . Plasma NGAL and serum cystatin C were superior to conventional biomarkers in the prediction of AKI and were also of prognostic value in this setting Neutrophil gelatinase‐associated lipocalin ( NGAL ) is a measure of acute kidney injury . Renal dysfunction portends significant risk after discharge from acute heart failure ( AHF ) . Thus , a sensitive marker of renal injury might also help to risk stratify HF patients OBJECTIVES The aim of this study was to test the hypothesis that , without diagnostic changes in serum creatinine , increased neutrophil gelatinase-associated lipocalin ( NGAL ) levels identify patients with sub clinical acute kidney injury ( AKI ) and therefore worse prognosis . BACKGROUND Neutrophil gelatinase-associated lipocalin detects sub clinical AKI hours to days before increases in serum creatinine indicate manifest loss of renal function . METHODS We analyzed pooled data from 2,322 critically ill patients with predominantly cardiorenal syndrome from 10 prospect i ve observational studies of NGAL . We used the terms NGAL(- ) or NGAL(+ ) according to study -specific NGAL cutoff for optimal AKI prediction and the terms sCREA(- ) or sCREA(+ ) according to consensus diagnostic increases in serum creatinine defining AKI . A priori-defined outcomes included need for renal replacement therapy ( primary endpoint ) , hospital mortality , their combination , and duration of stay in intensive care and in-hospital . RESULTS Of study patients , 1,296 ( 55.8 % ) were NGAL(-)/sCREA(- ) , 445 ( 19.2 % ) were NGAL(+)/sCREA(- ) , 107 ( 4.6 % ) were NGAL(-)/sCREA(+ ) , and 474 ( 20.4 % ) were NGAL(+)/sCREA(+ ) . According to the 4 study groups , there was a stepwise increase in subsequent renal replacement therapy initiation-NGAL(-)/sCREA(- ) : 0.0015 % versus NGAL(+)/sCREA(- ) : 2.5 % ( odds ratio : 16.4 , 95 % confidence interval : 3.6 to 76.9 , p < 0.001 ) , NGAL(-)/sCREA(+ ) : 7.5 % , and NGAL(+)/sCREA(+ ) : 8.0 % , respectively , hospital mortality ( 4.8 % , 12.4 % , 8.4 % , 14.7 % , respectively ) and their combination ( 4-group comparisons : all p < 0.001 ) . There was a similar and consistent progressive increase in median number of intensive care and in-hospital days with increasing biomarker positivity : NGAL(-)/sCREA(- ) : 4.2 and 8.8 days ; NGAL(+)/sCREA(- ) : 7.1 and 17.0 days ; NGAL(-)/sCREA(+ ) : 6.5 and 17.8 days ; NGAL(+)/sCREA(+ ) : 9.0 and 21.9 days ; 4-group comparisons : p = 0.003 and p = 0.040 , respectively . Urine and plasma NGAL indicated a similar outcome pattern . CONCLUSIONS In the absence of diagnostic increases in serum creatinine , NGAL detects patients with likely sub clinical AKI who have an increased risk of adverse outcomes . The concept and definition of AKI might need re- assessment We hypothesized that use of Schwartz formula underestimates the prevalence of CKD in PHT recipients . This study determined the prevalence and risk factors for CKD in PHT using novel methods -serum cystatin C , CKiD formula , Revised Schwartz formula , s- and u-NGAL . Serum BUN , creatinine , cystatin C and s- and u-NGAL were measured after prospect i ve enrollment . Schwartz formula GFR was compared with novel methods . CKD was defined as CKiD GFR < 90 mL/min/1.73 m(2 ) . The s- and u-NGAL were compared between those with and without CKD . Potential risk factors for CKD were analyzed . Seventy-nine patients ( 46 male children or boys ) , mean age 9.9 ± 5.8 yr formed the study cohort . The prevalence of mild and moderate CKD was 2- to 3-fold higher using novel methods compared to Schwartz formula . u-NGAL and u-NGAL/Cr were significantly higher in patients with CKD . u- and s-NGAL had negative correlation with estimates of GFR . Women were at a higher risk for CKD ( odds ratio 8.7 ) as was longer duration since transplant ( p = 0.009 ) . In conclusion , use of novel methods of GFR estimation unmasked 2- to 3-fold increased prevalence of CKD in PHT . Women and those with longer duration since transplant are at higher risk for CKD In very low birth weight ( VLBW ) infants , acute renal impairment ( ARI ) is common , but there is no consensus about criteria for its diagnosis . Neutrophil gelatinase-associated lipocalin ( NGAL ) is an early and sensitive indicator of renal impairment in experimental animals , children , and adults . Urinary NGAL ( UNGAL ) is detectable in VLBW infants ; however , there is no reference range in this population . The objective of this study is to define the reference range for UNGAL in VLBW infants with no risk factors for acute renal impairment . UNGAL concentration was determined in urine sample s collected from day of life ( DOL ) 4 through DOL 30 in 50 newborns with uncomplicated clinical courses , selected from a total of 145 prospect ively enrolled appropriate for gestational age inborn VLBW premature infants . The birth weight and gestational age ranges were 790 - 1490 g and 26–33 wk , respectively . The median , 95th and 99th percentiles , and range of pooled UNGAL values were 5 ng/mL , 50 ng/mL , 120 ng/mL , and 2–150 ng/mL , respectively . Greater variability and higher quantile levels of UNGAL were observed in females versus males . In conclusion , a reference range for UNGAL in VLBW infants , similar to that in children and adults , has been established Background / Aims : Contrast-induced nephropathy ( CIN ) is at present the third leading cause of hospital-acquired acute kidney injury ( AKI ) . Traditionally , it is diagnosed by measuring the increase of the serum creatinine concentration . However , in patients with acute changes in their glomerular filtration rate , serum creatinine is an insensitive marker . This clinical study was design ed to investigate whether human urinary interleukin-18 ( IL-18 ) and neutrophil gelatinase-associated lipocalin ( NGAL ) are early predictive markers for AKI after coronary angiography and their correlation with later cardiac events . Methods : Patients undergoing coronary angiography using low-osmolar contrast medium were enrolled and then followed up for at least 17 months . Urine sample s were collected before and 24 h after coronary angiography and IL-18 and NGAL levels measured by using an ELISA kit . Results : CIN was diagnosed in 13 of 150 ( 8.7 % ) patients ( CIN group ) ; 27 patients Output:	However , it is important to note that NGAL , in the absence of diagnostic increases in serum creatinine , is able to detect some patients affected by sub clinical AKI who have an increased risk of adverse outcomes .
MS2954	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Malignant pleural mesothelioma is a mainly asbestos-related neoplasm that occurs with increasing frequency and is associated with a poor prognosis . Extrapleural pneumonectomy which was initially performed as a st and -alone treatment in patients with resectable disease is now currently almost uniformly applied as part of a multi-modal approach . Its value and advantage over other therapeutic strategies remain points of discussion . We therefore analysed our experience with extrapleural pneumonectomy in the treatment of malignant pleural mesothelioma . METHODS We retrospectively review ed our institutional experience with all consecutive patients undergoing extrapleural pneumonectomy for malignant pleural mesothelioma from 1994 to 2005 . Patients were analysed with regard to hospital mortality and morbidity and long-term outcome . RESULTS Forty-nine patients ( 10 female/39 male , mean age 58 + 12 years ) underwent extrapleural pneumonectomy during the observation period . Median ICU stay was 1 day , median postoperative length of hospital stay was 13 days . After a mean follow-up of 2573 days , median survival was 376 days ( mean 672 + 121 days , range 9 - 3384 ) . One-year survival was 53 % , 3-year survival 27 % and 5-year survival 19 % . CONCLUSION Extrapleural pneumonectomy as part of a multi-modality treatment regimen is a good treatment option for selected patients with malignant pleural mesothelioma . The long-term results of this limited series compare favourably to non-surgical treatment regimens . Larger r and omised prospect i ve multi-centre trials are warranted to establish clear guidelines BACKGROUND Trimodality therapy seems to be the best treatment for malignant pleural mesothelioma ( MPM ) . A large experience served to evaluate the efficacy of surgery followed by adjuvant chemo-radiotherapy . Trimodality therapy results have led us to test induction chemotherapy followed by EPP and adjuvant radiotherapy in stages I-III of MPM . The aim of our study was to evaluate the feasibility of this protocol and to estimate survival . METHODS From 2000 to 2003 , 21 patients with MPM ( 14 males and 7 females , median age 59 years ) were enrolled in the prospect i ve study . Induction chemotherapy consisted of Carboplatin ( AUC 5mg/mL/min on Day 1 ) and Gemcitabine ( 1000mg/m(2 ) on Days 1 , 8 , 15 ) for three to four cycles . EPP was performed 3 - 5 weeks after induction therapy , while post-operative RT was given 4 - 6 weeks after operation . RESULTS Ten patients received three cycles of chemotherapy , 10 patients received four cycles and 1 patient had two cycles . Grade s 3 - 4 haematological toxicity occurred in eight ( 38.1 % ) patients . Chemotherapy response rate was : complete 0 % , partial 33.3 % and stable disease 66.7 % . Seventeen ( 80.9 % ) out of 21 patients underwent EPP with no intra or post-operative mortality with an overall major and minor morbidity rate at 52.4 % . Median survival was 25.5 months , with an overall 1 , 3 and 5-year survival rate of 71 , 33 and 19 % , respectively . CONCLUSIONS In MPM , the combined modality approach using the Carboplatin/Gemcitabine combination as induction chemotherapy is feasible , with good results in terms of survival and morbidity . Our results are similar to those of other studies using a heavier modality treatment Aprotinin has been used to decrease blood loss with complicated cardiac surgery but has not been investigated in extrapleural pneumonectomy , an operation that does not use cardiopulmonary bypass . In this prospect i ve , r and omized , placebo‐controlled , double‐blind trial , the authors investigated whether aprotinin decreased blood loss in patients who underwent this operation Abstract Background : We analyzed morbidity and mortality , sites of recurrence , and possible prognostic factors in 95 ( 78 male , 17 female ) patients with MPM on phase I – III trials since 1990 . A debulking resection to a requisite , residual tumor thickness of ≤ 5 mm was required for inclusion . Methods : Preoperative tumor volumes were determined by three-dimensional reconstruction of chest computerized tomograms . Pleurectomy ( n=39 ) or extrapleural pneumonectomy ( EPP ; n=39 ) was performed . Seventeen patients could not be debulked . Preoperative EPP platelet counts ( 404,000 ) and mean tumor volume ( 491 cm3 ) were greater than that seen for pleurectomy ( 344,000 , 114 cm3 ) . Results : Median survival for all patients was 11.2 months , with that for pleurectomy 14.5 months , that for EPP 9.4 months , and that for unresectable patients 5.0 months . Arrhythmia ( n=14 ; 15 % ) was the most common complication , and there were two deaths related to surgery ( 2.0 % ) . Tumor volume of > 100 ml , biphasic histology , male sex , and elevated platelet count were associated with decreased survival ( p<0.05 ) . Both EPP and pleurectomy had equivalent recurrence rates ( 27 of 39 [ 69 % ] and 31 of 39 [ 79 % ] , respectively ) ; however , 17 of 27 EPP recurrences as opposed to 28 of 31 pleurectomy recurrences were locoregional ( p2=0.013 ) . Conclusions : Debulking resections for MPM can be performed with low operative mortality . Size and platelet count are important preoperative prognostic parameters for MPM . Patients with poor prognostic indicators should probably enter nonsurgical , innovative trials where toxicity or response to therapy can be evaluated BACKGROUND The factors influencing outcome after resection of malignant pleural mesothelioma ( MPM ) are controversial . This analysis of a prospect i ve surgical data base identifies important prognostic factors . METHODS Tumors were staged by the International Mesothelioma Interest Group staging system , and patients were followed until death . Prognostic factors were analyzed by log rank and Cox regression , and were considered significant if p was less than 0.05 . RESULTS From Oct 1983 to May 1998 , 231 patients underwent thoracotomy , 115 had extrapleural pneumonectomy ( EPP ) , and 59 pleurectomy/decortication ( P/D ) . Among patients having EPP or P/D , 142 received adjuvant therapy . The median survival for stage I tumors was 29.9 months , for stage II 19 months , for stage III 10.4 months , and for stage IV 8 months . By multivariate analysis , stage , histology , gender , adjuvant therapy , but not the type of surgical resection , were significant . CONCLUSIONS The better survival previously reported for P/D compared with EPP is not seen in a large data base with long follow-up . Stages I and II have better survival rates than generally assumed for MPM . Locally advanced T and N status , and nonepithelial histology , identify poor prognosis patients who should be considered for novel treatment regimens OBJECTIVE The authors examine the feasibility and efficacy of trimodality therapy in the treatment of malignant pleural mesothelioma and identify prognostic factors . BACKGROUND Mesothelioma is a rare , uniformly fatal disease that has increased in incidence in recent decades . Single and bimodality therapies do not improve survival . METHODS From 1980 to 1995 , 120 patients underwent treatment for pathologically confirmed malignant mesothelioma at Brigham and Women 's Hospital and Dana-Farber Cancer Institute ( Boston , MA ) . Initial patient evaluation was performed by a multimodality team . Patients meeting selection criteria and with resectable disease identified by computed tomography scan or magnetic resonance imaging underwent extrapleural pneumonectomy followed by combination chemotherapy and radiotherapy . RESULTS The cohort included 27 women and 93 men with a mean age of 56 years . Operative mortality rate was 5.0 % , with a major morbidity rate of 22 % . Overall survival rates were 45 % at 2 years and 22 % at 5 years . Two and 5-year survival rates were 65 % and 27 % , respectively , for patients with epithelial cell type , and 20 % and 0 % , respectively , for patients with sarcomatous or mixed histology tumors . Nodal involvement was a significant negative prognostic factor . Patients who were node negative with epithelial histology had 2- and 5-year survival rates of 74 % and 39 % , respectively . Involvement of margins at time of resection did not affect survival , except in the case of full-thickness , transdiaphragmatic invasion . Classification on the basis of a revised staging system stratified median survivals , which were 22 , 17 , and 11 months for stages I , II , and III , respectively ( p = 0.04 ) . CONCLUSIONS Extrapleural pneumonectomy with adjuvant therapy is appropriate treatment for selected patients with malignant mesothelioma selected using a revised staging system PURPOSE Patients with malignant pleural mesothelioma , a rapidly progressing malignancy with a median survival time of 6 to 9 months , have previously responded poorly to chemotherapy . We conducted a phase III trial to determine whether treatment with pemetrexed and cisplatin results in survival time superior to that achieved with cisplatin alone . PATIENTS AND METHODS Chemotherapy-naive patients who were not eligible for curative surgery were r and omly assigned to receive pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 on day 1 , or cisplatin 75 mg/m2 on day 1 . Both regimens were given intravenously every 21 days . RESULTS A total of 456 patients were assigned : 226 received pemetrexed and cisplatin , 222 received cisplatin alone , and eight never received therapy . Median survival time in the pemetrexed/cisplatin arm was 12.1 months versus 9.3 months in the control arm ( P = .020 , two-sided log-rank test ) . The hazard ratio for death of patients in the pemetrexed/cisplatin arm versus those in the control arm was 0.77 . Median time to progression was significantly longer in the pemetrexed/cisplatin arm : 5.7 months versus 3.9 months ( P = .001 ) . Response rates were 41.3 % in the pemetrexed/cisplatin arm versus 16.7 % in the control arm ( P < .0001 ) . After 117 patients had enrolled , folic acid and vitamin B12 were added to reduce toxicity , result ing in a significant reduction in toxicities in the pemetrexed/cisplatin arm . CONCLUSION Treatment with pemetrexed plus cisplatin and vitamin supplementation result ed in superior survival time , time to progression , and response rates compared with treatment with cisplatin alone in patients with malignant pleural mesothelioma . Addition of folic acid and vitamin B12 significantly reduced toxicity without adversely affecting survival time BACKGROUND The aim of this multicenter trial was to prospect ively evaluate neo-adjuvant chemotherapy followed by extrapleural pneumonectomy ( EPP ) and radiotherapy , including quality of life as outcome . PATIENTS AND METHODS Eligible patients had malignant pleural mesothelioma of all histological types , World Health Organization performance status of zero to two and clinical stage T1-T3 , N0 - 2 , M0 disease considered completely resectable . Neo-adjuvant chemotherapy consisted of three cycles of cisplatin and gemcitabine followed by EPP . Postoperative radiotherapy was considered for all patients . RESULTS In all , 58 of 61 patients completed three cycles of neo-adjuvant chemotherapy . Forty-five patients ( 74 % ) underwent EPP and in 37 patients ( 61 % ) the resection was complete . Postoperative radiotherapy was initiated in 36 patients . The median survival of all patients was 19.8 months [ 95 % confidence interval ( CI ) 14.6 - 24.5 ] . For the 45 patients undergoing EPP , the median survival was 23 months ( 95 % CI 16.6 - 32.9 ) . Psychological distress showed minor variations over time with distress above the cut-off score indicating no morbidity with 82 % ( N = 36 ) at baseline and 76 % ( N = 26 ) at 3 months after surgery ( P = 0.5 ) . CONCLUSIONS The observed rate of operability is promising . A median survival of 23 months for patients undergoing EPP compares favourably with the survival reported from single center studies of upfront surgery . This approach was not associated with an increase in psychological distress OBJECTIVE To report on the experience with radical surgery , with emphasis on the long-term outcome , for malignant pleural mesothelioma ( MPM ) at a single institution . METHODS From our prospect i ve data base over a Output:	DISCUSSION S The current evidence suggests that selected patients with malignant pleural mesothelioma may benefit from EPP , especially when combined with neoadjuvant or adjuvant chemotherapy and adjuvant radiotherapy
MS2955	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background High prevalence rates of Chlamydia trachomatis ( CT ) and Neisseria gonorrhoeae ( NG ) have been reported in Aboriginal people in remote and regional areas of Australia for well over two decades , and repeat positivity rates are high . To interrupt disease transmission and reduce the risk of complications , early diagnosis and treatment is important . However in many remote and regional areas there are long delays between testing for these curable sexually transmissible infections and providing treatment , due to both physical distance from laboratories and difficulties when recalling patients for subsequent management once results are available . Point-of-care ( POC ) tests have the potential to provide more timely diagnosis , to increase treatment and contact tracing , and in turn reduce CT and NG infection rates . Methods / design TTANGO ( Test , Treat , ANd GO ) is a cross-over cluster r and omised controlled trial in 12 regional or remote Australian health services , which predominantly provide clinical services to Aboriginal people . The overall aim of TTANGO is to measure the clinical effectiveness , cost-effectiveness and cultural and operational acceptability of molecular POC testing for CT and NG infection . The primary outcome is repeat positivity at three months after treatment of an initial CT or NG infection . Participating health services will undertake the clinical management of CT and NG under two different modalities for one year each . In the first year , six health services will be r and omly assigned to manage these infections under current diagnostic guidelines . The other six will supplement current diagnostic guidelines with POC testing , whereby diagnosis is made and subsequent treatment for those with positive POC tests is offered at the initial consultation . In the second year , the health services will cross over to the opposite management modality . TTANGO will be conducted over four years ; 1.5 years of trial initiation and community consultation , 2 years of trial conditions and evaluation , and 6 months of data analysis and feedback . Discussion TTANGO is the first cluster r and omised trial of POC testing for CT and NG internationally . The results of this trial will provide crucial information to guide sexual health clinical practice in remote Aboriginal communities and other high prevalence setting s . Trial registration Australian and New Zeal and Clinical Trials Registry Objective To evaluate the effectiveness of register based , yearly chlamydia screening . Design Controlled trial with r and omised stepped wedge implementation in three blocks . Setting Three regions of the Netherl and s : Amsterdam , Rotterdam , and South Limburg . Participants 317 304 women and men aged 16 - 29 years listed on municipal registers at start of trial . Intervention From March 2008 to February 2011 , the Chlamydia Screening Implementation programme offered yearly chlamydia screening tests . Postal invitations asked people to use an internet site to request a kit for self collection of sample s , which would then be sent to regional laboratories for testing . Treatment and partner notification were done by the general practitioner or at a sexually transmitted infection clinic . Main outcome measures Primary outcomes were the percentage of chlamydia tests positive ( positivity ) , percentage of invitees returning a specimen ( uptake ) , and estimated chlamydia prevalence . Secondary outcomes were positivity according to sex , age , region , and sociodemographic factors ; adherence to screening invitations ; and incidence of self reported pelvic inflammatory disease . Results The participation rate was 16.1 % ( 43 358/269 273 ) after the first invitation , 10.8 % after the second , and 9.5 % after the third , compared with 13.0 % ( 6223/48 031 ) in the control block invited at the end of round two of the intervention . Chlamydia positivity in the intervention blocks at the first invitation was the same as in the control block ( 4.3 % ) and 0.2 % lower at the third invitation ( odds ratio 0.96 ( 95 % confidence interval 0.83 to 1.10 ) ) . No substantial decreases in positivity were seen after three screening rounds in any region or sociodemographic group . Among the people who participated three times ( 2.8 % of all invitees ) , positivity fell from 5.9 % to 2.9 % ( odds ratio 0.49 ( 0.47 to 0.50 ) ) . Conclusions There was no statistical evidence of an impact on chlamydia positivity rates or estimated population prevalence from the Chlamydia Screening Implementation programme after three years at the participation levels obtained . The current evidence does not support a national roll out of this register based chlamydia screening programme . Trial registration NTR 3071 ( Netherl and s Trial Register , www.trialregister.nl ) Abstract Background High blood pressure in patients with stroke increases the risk of recurrence but management in the community is often inadequate . Home blood pressure monitoring may increase patients ' involvement in their care , increase compliance , and reduce the need for patients to attend their General Practitioner if blood pressure is adequately controlled . However the value of home monitoring to improve blood pressure control is unclear . In particular its use has not been evaluated in stroke patients in whom neurological and cognitive ability may present unique challenges . Design Community based r and omised trial with follow up after 12 months . Participants : 360 patients admitted to three South London Stroke units with stroke or transient ischaemic attack within the past 9 months will be recruited from the wards or out patients and r and omly allocated into two groups . All patients will be visited by the specialist nurse at home at baseline when she will measure their blood pressure and administer a question naire . These procedures will be repeated at 12 months follow up by another research er blind as to whether the patient is in intervention or control group . Intervention : Intervention patients will be given a vali date d home blood pressure monitor and support from the specialist nurse . Control patients will continue with usual care ( blood pressure monitoring by their practice ) . Main outcome measures in both groups after 12 months : 1 . Change in systolic blood pressure.2 . Cost effectiveness : Incremental cost of the intervention to the National Health Service and incremental cost per quality adjusted life year gained . Trial registration Clinical Trials.gov registration OBJECTIVE The objective of the study was to estimate whether midpregnancy genitourinary tract infection with Chlamydia trachomatis is associated with an increased risk of subsequent preterm delivery . STUDY DESIGN Infection with C. trachomatis was determined using a ligase chain reaction assay ( performed in batch after delivery ) of voided urine sample s collected at the r and omization visit ( 16(0/7 ) to 23(6/7 ) weeks ' gestation ) and the follow-up visit ( 24(0/7 ) to 29(6/7 ) weeks ) among 2470 gravide women with bacterial vaginosis or Trichomonas vaginalis infection enrolled in 2 multicenter r and omized antibiotic treatment trials ( metronidazole versus . placebo ) . RESULTS The overall prevalence of genitourinary tract C. trachomatis infection at both visits was 10 % . Preterm delivery less than 37 weeks ' or less than 35 weeks ' gestational age was not associated with the presence or absence of C. trachomatis infection at either the r and omization ( less than 37 weeks : 14 % versus 13 % , P=.58 ; less than 35 weeks : 6.4 % versus 5.5 % , P=.55 ) or the follow-up visit ( less than 37 weeks : 13 % versus 11 % , P=.33 ; less than 35 weeks : 4.4 % versus 3.7 , P=.62 ) . Treatment with an antibiotic effective against chlamydia infection was not associated with a statistically significant difference in preterm delivery . CONCLUSION In this secondary analysis , midtrimester chlamydia infection was not associated with an increased risk of preterm birth . Treatment of chlamydia was not associated with a decreased frequency of preterm birth The objective of this research was to identify determinants of the magnitude of intracluster correlation coefficients ( ICCs ) in cluster r and omized trials from the field of implementation research . A survey of experts was conducted to generate a priori hypotheses of factors that might affect ICC size . Hypotheses were tested on empirical estimates of ICCs calculated from 21 implementation research data sets , mainly from the UK . Effects of setting ( primary or secondary care ) , type of variable ( process or outcome ) , type of measurement ( objective or subjective ) , prevalence of outcome and size of cluster were tested . In total , 220 ICCs were available ( range 0 to 0.415 ) . Significant differences in ICC magnitude were found . The ICCs were significantly higher for process than for outcome variables , and for secondary care outcomes compared with primary care outcomes . The effects of prevalence and size were less clear cut . There was no evidence to suggest that type of measurement affected ICC size . In conclusion , accurate estimates of ICCs are essential for sample size calculations for cluster r and omized trials of professional behaviour change interventions . This study demonstrates that ICCs are sensitive to a number of trial factors , particularly setting and outcome type . These factors must be considered when planning such cluster r and omized trials OBJECTIVE To determine whether asking general practitioners to offer chlamydia screening at the same time as Pap screening increases chlamydia screening rates . DESIGN A pragmatic cluster r and omised controlled trial . PARTICIPANTS AND SETTING Doctors from 31 general practice s in the Australian Capital Territory performing more than 15 Pap smear screens per year , and all women aged 16 - 39 years attending those practitioners between 1 November 2004 and 31 October 2005 . INTERVENTION Doctors in the intervention practice s were asked to routinely offer combined chlamydia and Pap screening to eligible women ; doctors in the control practice s were asked to implement screening guidelines based on a risk assessment of the individual patient ( ie , usual practice ) . MAIN OUTCOME MEASURE Chlamydia screening rate per visit . RESULTS There were 26 876 visits by eligible women during the study period : 16 082 to intervention practice s and 10 794 to control practice s. Chlamydia screening occurred during 6.9 % ( 95 % CI , 6.5%-7.3 % ) of visits to intervention practice s and 4.5 % ( 95 % CI , 4.1%-4.9 % ) of visits to control practice s. After controlling for clustering and potential confounders , there were twofold greater odds of chlamydia screening occurring during a visit by an eligible woman to an intervention practice than to a control practice ( adjusted odds ratio , 2.1 [ 95 % CI , 1.3 - 3.4 ] ) . CONCLUSION Combining chlamydia and Pap screening increases the rate of chlamydia screening in general practice . Implementing this approach would require little additional infrastructure support in setting s where a cervical screening program already exists Background Sexual health problems such as unwanted pregnancy and sexually transmitted infection are important public health concerns and there is huge potential for health promotion using digital interventions . Evaluations of digital interventions are increasingly conducted online . Trial administration and data collection online offers many advantages , but concerns remain over fraudulent registration to obtain compensation , the quality of self-reported data , and high attrition . Objective This study addresses the feasibility of several dimensions of online trial design —recruitment , online consent , participant identity verification , r and omization and concealment of allocation , online data collection , data quality , and retention at 3-month follow-up . Methods Young people aged 16 to 20 years and resident in the United Kingdom were recruited to the “ Sexunzipped ” online trial between November 2010 and March 2011 ( n=2036 ) . Participants filled in baseline demographic and sexual health question naires online and were r and omized to the Sexunzipped interactive intervention website or to an information-only control website . Participants were also r and omly allocated to a postal request ( or no request ) for a urine sample for genital chlamydia testing and receipt of a lower ( £ 10/US$16 ) or higher ( £ 20/US$32 ) value shopping voucher compensation for 3-month outcome data . Results The majority of the 2006 valid participants ( 90.98 % , 1825/2006 ) were aged between 18 and 20 years at enrolment , from all four countries in the United Kingdom . Most were white ( 89.98 % , 1805/2006 ) , most were in school or training ( 77.48 % , 1545/1994 ) , and 62.81 % ( 1260/2006 ) of the sample were female . In total , 3.88 % ( 79/2036 ) of registration s appeared to be invalid and another 4.00 % ( 81/2006 ) of participants gave inconsistent responses within the question naire . The higher value compensation ( £ 20/US$32 ) increased response rates by 6 - 10 % , boosting retention at 3 months to 77.2 % ( 166/215 ) for su bmi ssion of online self-reported sexual health outcomes and 47.4 % ( 118/249 ) for return of chlamydia urine sample s by post . Conclusions It was quick and efficient to recruit young people to this online trial . Our procedures for obtaining online consent , verifying participant identity , automated r and omization , and concealment of allocation worked well . The optimal response rate for the online sexual health outcome measurement was comparable to face-to-face trials . Multiple methods of participant contact , requesting online data only , and higher value compensation increased trial retention at 3-month follow-up . Trial Registration International St and ard R and omized Controlled Trial Number ( IS RCT N ) : 55651027 ; http://www.controlled-trials.com/IS RCT N55651027 ( Arch Output:	There is moderate quality evidence that detection and treatment of chlamydia infection can reduce the risk of PID in women at individual level . There is an absence of RCT evidence about the effects of chlamydia screening in pregnancy .
MS2956	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Twenty-six patients were recruited for a study of the safety and efficacy of immunotherapy with IPG . They were r and omly assigned to two groups based on skin test titrations to grass allergens . One group was treated in a double-blind fashion before the 1982 grass season with 12 weekly injections totaling approximately 48,000 PNU , and the other group was treated with 12 weekly injections of caramelized glucose histamine placebo . Daily symptom and medication score sheets were completed by all patients each day of the grass season . Blocking antibody rose ninefold in the IPG group ( p less than 0.007 ) but was unchanged in the placebo group . There was no significant change in IgE against rye grass group I in either the IPG or the placebo group . Symptom-score mean in the IPG group was 217 + /- 71 ( S.E.M. ) , statistically lower ( p less than 0.02 ) than the mean in the placebo group 496 + /- 117 ( S.E.M. ) . There were no systemic reactions and only minor local reactions . There was no change in routine laboratory tests in either group . Although two prior studies with grass allergen immunotherapy reported efficacy , these studies did not use symptom-score analysis . This is the first double-blind , histamine placebo-controlled study of grass immunotherapy that demonstrates efficacy by symptom-score index evaluation . IPG is a safe , clinical ly effective , and potentially cost-effective therapy for grass pollinosis BACKGROUND The natural history of allergic sensitization is complex and poorly understood . A prospect i ve nonr and omized study was carried out in a population of asthmatic children younger than 6 years of age whose only allergic sensitivity was to house dust mites ( HDMs ) . OBJECTIVES The study was design ed to determine whether specific immunotherapy ( SIT ) with st and ardized allergen extracts could prevent the development of new sensitizations over a 3-year follow-up survey . METHODS We studied 22 children monosensitized to HDM who were receiving SIT with st and ardized allergen extracts and 22 other age-matched control subjects who were monosensitized to HDM . The initial investigation included a full clinical history , skin tests with a panel of st and ardized allergens , and the measurement of allergen-specific IgE , depending on the results of skin tests . Children were followed up on an annual basis for 3 years , and the development of new sensitizations in each group was recorded . RESULTS Ten of 22 children monosensitized to HDM who were receiving SIT did not have new sensitivities compared with zero of 22 children in the control group ( p = 0.001 , chi square test ) . CONCLUSIONS This study suggests that SIT in children monosensitized to HDM alters the natural course of allergy in preventing the development of new sensitizations Background : The clinical efficacy and safety of a six‐grass pollen allergoid has been studied . The advent of more exacting clinical guidelines and a better appreciation of the possible mechanisms of treatment prompted this re appraisal BACKGROUND The efficacy and safety of the 300-index of reactivity ( IR ) dose of 5-grass-pollen sublingual immunotherapy ( SLIT ) tablets ( Stallergènes , Antony , France ) have been demonstrated for the treatment of hay fever in adults . OBJECTIVE We sought to assess the efficacy and safety of this tablet in children and adolescents with grass pollen-related allergic rhinitis . METHODS In this multinational , r and omized , double-blind , placebo-controlled study , 278 children ( 5 - 17 years of age ) with grass pollen-related rhinoconjunctivitis ( confirmed by means of a positive grass pollen skin prick test response and serum-specific IgE measurement ) received once-daily SLIT tablets or placebo . Treatment was initiated 4 months before the estimated pollen season and continued throughout the season . The primary outcome was the rhinoconjunctivitis total symptom score ( RTSS ) , a sum of 6 individual symptom scores : sneezing , runny nose , itchy nose , nasal congestion , watery eyes , and itchy eyes . Secondary end points included rescue medication intake , individual scores , and safety . RESULTS The intent-to-treat population included 266 children ( mean age , 10.9 + /- 3.22 years ) . The RTSS for the 300-IR group was highly significantly different from that of the placebo group ( P = .001 ) . The 300-IR group showed a mean improvement for the RTSS of 28.0 % over that seen with placebo and a median improvement of 39.3 % . Significant differences between the 300-IR and placebo groups were also observed regarding rescue medication score and proportion of days using rescue medication during the pollen season ( P = .0064 and P = .0146 , respectively ) . Adverse events were generally mild or moderate in intensity and expected . No serious side effects were reported . CONCLUSION Five-grass-pollen SLIT tablets ( 300 IR ) reduce both symptom scores and rescue medication use in children and adolescents with grass pollen-related rhinoconjunctivitis Background : Data supporting a carry‐over effect with sublingual immunotherapy ( SLIT ) are scarce . This r and omized , double‐blind , placebo‐controlled study evaluated the efficacy , carry‐over effect and safety of grass pollen SLIT using co‐seasonal treatment BACKGROUND This is an interim analysis of a r and omized , double-blind , placebo-controlled phase III trial with 3 years of daily treatment with grass tablet immunotherapy ( GRAZAX ; ALK-Abelló A/S , Hørsholm , Denmark ) or placebo , followed by 2 years of follow-up to assess the persistent efficacy . OBJECTIVE We sought to evaluate the efficacy and safety of specific immunotherapy with grass allergen tablets compared with placebo after treatment covering 2 consecutive grass pollen seasons . METHODS The interim analyses included 351 adult participants with moderate-to-severe allergic rhinoconjunctivitis caused by grass pollen . Participants were treated with active ( n = 189 ) or placebo ( n = 162 ) tablets for an average of 22 months . All participants were allowed to use symptomatic rescue medication . RESULTS The primary efficacy analysis showed highly significant mean reductions of 36 % in rhinoconjunctivitis symptom score ( P < .0001 ; median reduction , 44 % ) and 46 % in rhinoconjunctivitis medication score ( P < .0001 ; median reduction , 73 % ) in the active group relative to the placebo group . Mean rhinoconjunctivitis quality of life was 33 % better ( P < .0001 ; median , 40 % ) . Clinical improvements were paralleled by significant changes in allergen-specific immunoglobulins . The treatment was well tolerated , and adverse events led to withdrawal in less than 1 % of participants . There were no serious adverse events related to treatment . CONCLUSION Grass allergen tablet immunotherapy showed progressive immunologic changes and highly significant efficacy over 2 years of continued treatment Sublingual immunotherapy ( SLIT ) with monomeric carbamylated allergoid administered in accordance with the st and ard regimen has proven to be effective and safe . Achieving clinical benefit , however , requires a lengthy period of time so it is not very suitable for short-lasting allergies . We thus performed this study to compare an administration protocol starting in the coseasonal period ( with a 4-day build-up phase ) with a precoseasonal scheme to verify if the former regimen provides the same benefit in a shorter period of time . The prospect i ve , r and omized , drug therapy-controlled study was conducted in 33 rhinitic patients monosensitized to Olea with or without asthma . Ten patients were assigned to the coseasonal therapy with 5000 allergic units (AU)/week for 6 weeks , 11 to the precoseasonal therapy with 3000 AU/week for 10 weeks , and 12 to drug therapy . They were treated from April or May to June 2008 . A visual analog scale ( VAS ) was performed at baseline and after treatment to assess the well being of the patients . Drug consumption was evaluated by means of a monthly diary . There was greater VAS improvement in both the SLIT groups versus the controls , but it was statistically significant only in the coseasonal group ( p < 0.01 ) . Furthermore , there was a reduction in the rescue medication only in the coseasonal SLIT ( p < 0.05 versus drug therapy ) . One mild adverse event was observed . The allergoid SLIT was shown to be effective and safe in Olea allergy in particular when a coseasonal regimen was used BACKGROUND The safety and efficacy of specific immunotherapy for mold allergy are not known in children and adolescents . OBJECTIVE We evaluated the efficacy and safety of specific immunotherapy with a st and ardized allergen extract in a r and omized , double-blind , placebo-controlled , 3-year prospect i ve study of patients who were allergic to only Alternaria alternata . METHODS Fifty children and adolescents ( 25 girls ; 5 - 18 years of age ) with A alternata-induced seasonal allergic rhinoconjunctivitis and /or bronchial asthma were r and omly assigned to groups given treatment ( Novo-Helisen Depot , A alternata 100 % ) or placebo . The primary end point was the combined symptom medication score . Secondary end points included safety , quality of life , and sensitivity to allergen-specific nasal challenge . RESULTS Forty-five children completed the 3-year study . Although there was no significant change in year 1 , the combined symptom medication score decreased in years 2 and 3 of the study ( by 38.7 % and 63.5 % , respectively ; P < .001 for each ) . The reduction in symptoms was associated with a significant improvement in quality of life ( P < .05 ) and decrease in sensitivity after allergen-specific nasal challenge . Side effects were observed in 7 patients ; the most common ( edema at the site of injection ) occurred after 11 injections . CONCLUSIONS Allergen-specific immunotherapy with st and ardized A alternata extract reduces symptoms of asthma and rhinoconjunctivitis in children and adolescents without serious side effects Background : Local application of allergen extracts in specific immunotherapy is accompanied by increased compliance and significantly reduced side effects . However , efficacy of local immunotherapy in children has yet not been sufficiently demonstrated . This study was performed to determine clinical efficacy of high dose sublingual swallow immunotherapy ( SLIT ) by a double‐blind placebo‐controlled study in children with grass pollen allergy using high dose allergen extracts UNLABELLED SAFETY and efficacy of sublingual ( sublingual-swallow ) immunotherapy ( IT ) with house dust mite extract were evaluated in 30 children ( 6 - 15 2/3 years of age ) over the first 12 months of an ongoing study . The cumulative dose was 570 micrograms Der p I ( five times that administered with subcutaneous therapy ) . SAFETY One patient on active treatment dropped out after 8 weeks because of a subjective feeling of severe weakness , question ably induced by the therapy . Five patients on active therapy and one patient on placebo reported minor local side effects . EFFICACY Pulmonary symptoms were reduced after 12 months in actively treated asthmatics , but this was not consistent with the lack of improvement in bronchial reactivity , skin sensitivity and specific IgG and IgG4 against D.pt . in this group . In patients with rhinitis nasal sensitivity was reduced in the placebo group without concomitant improvement in the nasal symptom score . Specific IgE ( D.pt . and D.f . ) increased significantly more in the active treatment group after 3 and 12 months . We conclude that sublingual IT over 12 months with the fivefold Der p 1 dose of subcutaneous IT was well tolerated , but there was no consistent clinical or immunological benefit compared to placebo A double-blind , placebo-controlled study of immunotherapy was conducted in 31 patients with allergic rhinitis due to Parietaria pollen to evaluate the efficacy and safety of high doses of allergen via the sublingual route . The patients were assessed before and after a 10-month period of treatment by clinical ( symptom-medication scores and specific nasal reactivity ) and immunological ( total IgE , specific IgE , IgG and IgG4 antibodies ) parameters . High doses of Parietaria extract corresponding to a cumulative dose of 105 BU for each patient were administered with negligible side effects . The actively treated patients had significantly lower medication scores than those on placebo ( p < 0.05 ) when the maximum pollen count was recorded , and at the end of the trial they showed a significant decrease in nasal reactivity ( p < 0.02 ) and a significant increase in serum specific IgG4 ( p = 0.02 ) . No differences were detected in any of these parameters in the placebo group . Possible explanations for the mechanisms of sublingual immunotherapy are proposed OBJECTIVE To evaluate the safety and efficacy of sublingual immunotherapy with ' Dermatophagoides Farinae Drops ' in D. farinae allergic asthma and /or rhinitis patients . METHODS A 25-week double-blind , placebo-controlled , multi-centered trail was conducted in 278 children ( aged 4 - 18 yr ) with mite-induced asthma and /or rhinitis . Patients were r and omly assigned to receive sublingual immunotherapy ( SLIT ) with ' Dermatophagoides Farinae Output:	RESULTS Meta-analyses found statistically significant effects for SCIT and SLIT compared with placebo across a number of outcome measures and for the vast majority of subgroup analyses ( type and amount of allergen , duration of treatment ) . There was less evidence for children , but some results in favour of SLIT were statistically significant . Indirect comparisons did not provide conclusive results in favour of either SCIT or SLIT . A benefit from both SCIT and SLIT compared with placebo has been consistently demonstrated , but the extent of this effectiveness in terms of clinical benefit is unclear .
MS2957	*TASK* the task is to summarize an input biomedical literature in six sentences *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 article reports on the evidence for the validity of psychotic major depression as a distinct subtype based on cross-sectional and 1-year prospect i ve data from the Epidemiologic Catchment Area study . Consistent with findings from previous clinical studies , only about 14 % of major depressions were accompanied by psychotic features . Psychotic as compared with nonpsychotic depression had a more severe course , as reflected in increased risk of relapse , persistence over 1 year , suicide attempts , hospitalization , comorbidity , and financial dependency . These differences could not be explained by differences in demographic characteristics or by symptom severity , as assessed by symptom profile or number of symptoms . The boundary problem with schizophrenia and bipolar affective disorder that is seen in clinical studies was also found in this sample . To our knowledge , this is the first study to examine the validity of psychotic depression in a community sample ; the findings are consistent with those from clinical sample s. They support the clinical significance of psychotic depression and the continuation of its inclusion as a distinct subtype in DSM-IV OBJECTIVE To examine the association between baseline suicidality and outcome of major depression in a r and omized controlled trial of the pharmacotherapy of psychotic depression and to explore the interaction of suicidality , r and omized treatment assignment , and depression outcome . METHODS This study was a secondary analysis of data from 258 persons aged 18 years or older with DSM-IV-defined major depressive disorder with psychotic features who participated in a 12-week r and omized controlled trial ( RCT ) comparing olanzapine plus sertraline with olanzapine plus placebo ( the Study of the Pharmacotherapy of Psychotic Depression [ STOP-PD ] , which ran from 2002 to 2007 ) . The independent variable was baseline suicidality , defined by 4 groups ( suicide attempt in the current episode , active suicidal ideation , passive suicidal ideation , and no suicidality ) . The outcome variables were change in 16-item Hamilton Depression Rating Scale ( HDRS₁₆ ) total score ( excluding the suicide item ) over time and remission of psychotic depression over time . RESULTS Suicidality groups did not significantly differ on baseline HDRS₁₆ total score . Baseline suicidality group was significantly associated with change in HDRS₁₆ score over time in the sample as a whole ( F₃,₁₃₉₄ = 8.17 ; P < .0001 ) , but was not significantly associated with probability of remission over time . Among participants assigned to olanzapine and placebo , persons with no suicidality had a significantly greater reduction in HDRS₁₆ total score compared to those with passive suicidal ideation ( 7.5-point difference in change scores between the 2 groups ; 95 % CI , 4.3 - 10.7 t₁₃₉₄ = 4.61 , P < .0001 ) , active suicidal ideation ( 4.4 points ; 95 % CI , 1.4 - 7.4 ; t₁₃₉₄ = 2.85 , P = .0176 ) , or suicide attempts ( 6.1 points ; 95 % CI , 2.8 - 9.4 ; t₁₃₉₄ = 3.66 , P = .0015 ) . The 12-week change from baseline in HDRS₁₆ score for patients with no suicidality was not significantly different between the 2 treatment arms . However , the 12-week HDRS₁₆ improvement was significantly greater in the olanzapine plus sertraline arm , compared with the olanzapine plus placebo arm , for patients with suicide attempts ( 8.7-point difference in change scores between the 2 groups ; 95 % CI , 5.1 - 12.4 ; t₁₃₉₄ = 4.75 , P < .0001 ) , active suicidal ideation ( 8.1 points ; 95 % CI , 4.5 - 11.7 ; t₁₃₉₄ = 4.38 , P < .0001 ) , or passive suicidal ideation ( 5.7 points ; 95 % CI , 2.2 - 9.2 ; t₁₃₉₄ = 3.23 , P = .0012 ) , respectively . CONCLUSIONS Baseline suicidality predicted worse acute treatment outcome of psychotic depression . However , participants with suicidality had a better outcome when treated with the combination of olanzapine and sertraline than when treated with olanzapine plus placebo . TRIAL REGISTRATION Clinical Trials.gov identifier : Objective To compare the relative efficacy of electroconvulsive therapy ( ECT ) in psychotic and nonpsychotic patients with unipolar major depression . Methods The outcome of an acute ECT course in 253 patients with nonpsychotic ( n = 176 ) and psychotic ( n = 77 ) unipolar major depression was assessed in the first phase of an ongoing National Institute of Mental Health-supported four-hospital collaborative study of continuation treatments after successful ECT courses . ECT was administered with bilateral electrode placement at 50 % above the titrated seizure threshold . The remission criteria were rigorous : a score ≤10 on the 24-item Hamilton Rating Scale for Depression ( HRSD ) after 2 consecutive treatments , and a decrease of at least 60 % from baseline . Results The overall remission rate was 87 % for study completers . Among these , patients with psychotic depression had a remission rate of 95 % and those with nonpsychotic depression , 83 % . Improvement in symptomatology , measured by the HRSD , was more robust and appeared sooner in the psychotic patients compared with the nonpsychotic patients . Conclusion Bilateral ECT is effective in relieving severe major depression . Remission rates are higher and occur earlier in psychotic depressed patients than in nonpsychotic depressed patients . These data support the argument that psychotic depression is a distinguishable nosological entity that warrants separate treatment algorithms The authors report prospect i ve uniform clinical data differentiating 25 patients who committed suicide from 929 patients who did not in a group of 954 patients with major affective disorder followed for an average of 4 years in the Collaborative Program on the Psychobiology of Depression . Eight ( 32 % ) of the suicides occurred within 6 months and 13 ( 52 % ) within 1 year of entry into the study . Hopelessness , loss of pleasure or interest , and mood cycling during the index episode differentiated the suicide group . Diagnostic subcategories , suicidal ideation at entry to the study , suicide attempts during current or past episodes , and medical severity of prior attempts did not differentiate the suicide group OBJECTIVE The present study investigates how consistently DSM-IV major depressive disorder ( MDD ) with psychosis was diagnosed by research consensus across 10 years and the association of clinical characteristics with diagnostic consistency . METHOD The sample included 146 participants , part of a larger first-admission cohort ( N = 628 ) presenting to a psychiatric inpatient facility with psychosis , who were diagnosed with psychotic depression at least once across 4 assessment s spanning 10 years ( after first admission and at 6-month , 24-month , and 10-year follow-ups ) . The primary outcome of this prospect i ve epidemiologic study was retention of the best-estimate consensus diagnosis at each assessment . Diagnoses at each assessment were determined from semistructured interviews , medical records , and informant reports . The participants were recruited from 1989 to 1995 . RESULTS Fifty-five of the 146 participants ( 37.7 % ) were diagnosed with psychotic depression at each available assessment ; 13 ( 8.9 % ) switched from MDD to bipolar disorder , 24 ( 16.4 % ) switched from MDD to schizophrenia or schizoaffective disorder , and the remaining 54 ( 37.0 % ) had other patterns of diagnostic change . Only 47 of 80 participants ( 58.8 % ) diagnosed with MDD at baseline retained a mood disorder diagnosis 10 years later ( 36 [ 45.0 % ] had MDD and 11 [ 13.8 % ] had bipolar disorder ) , while 16 of 52 participants ( 30.8 % ) who ended the study with MDD were initially misdiagnosed . Compared to participants who were consistently diagnosed with MDD , those switching from MDD to bipolar disorder had better premorbid adjustment , more first-degree relatives with MDD , better functioning , and fewer negative symptoms at baseline , whereas those shifting to the schizophrenia spectrum had a more insidious onset , longer initial hospital stays , worse functioning , and more negative symptoms ( all P values < .05 ) . CONCLUSIONS The diagnosis of MDD with psychosis among in patients showed poor long-term consistency . For clinicians , results indicate that the diagnosis of MDD with psychosis based on a single assessment should be considered provisional OBJECTIVE Most efforts to describe the prognostic significance of psychotic features in depression have been limited to single assessment s 1 year or less after the initial evaluation . However , the various biological and treatment response differences between patients with psychotic and nonpsychotic depression suggest that prognostic differences may be very long-term . METHOD The 787 patients described here entered the study as they sought treatment at one of five academic medical centers ; they had either RDC major depressive disorder or schizo-affective depression ( other than the mainly schizophrenic subtype ) and completed at least 6 months of follow-up . Of these , 144 ( 18.3 % ) had psychotic depression as defined here . Patients provided follow-up interviews at 6-month intervals for 5 years and annually thereafter ; 98 of those with psychotic depression and 434 of those with non-psychotic depression were followed for 10 years . RESULTS Those who began follow-up with psychotic depression had fewer weeks with minimal symptoms in each of the 10 years of follow-up and reported more psychosocial impairment at both 5 and 10 years . Both the index episode and the first recurrence of psychotic depression lasted longer than nonpsychotic episodes , but nonpsychotic episodes among previously psychotic individuals were relatively brief . Intervals between episodes were significantly shorter for patients who had ever been psychotic . CONCLUSIONS Together with evidence that psychotic features are highly recurrent , these data show 1 ) that psychotic features denote a lifetime illness of greater severity and 2 ) that within individuals , psychotic features may emerge in only the more severe episodes To evaluate the role of severe depression , i.e. , depression with melancholic and /or psychotic features and alcohol dependence in suicide and undetermined death . The Lundby Study is a prospect i ve , longitudinal study of a population consisting of 3563 subjects . In a long-term follow up 1947–2006 there were 66 suicide cases , including 19 undetermined deaths . Depression and alcoholism were as expected the major contributors to suicide ( 44 % and 23 % respectively ) . Severe depression with psychotic and /or melancholic features was diagnosed in 66 % of all depressions and in 29 % of all suicide cases , as compared to 15 % for major depression only . Alcohol dependence was related to undetermined death . Major depressive disorder with melancholic and /or psychotic features appears to be an important contributor to accomplished suicide in the depression group , and alcohol dependence appears to be related to undetermined death This retrospective study compared the treatment responses of 34 primary , unipolar depressives without psychotic features and 30 with psychotic features . Patients were diagnosed by Research Diagnostic Criteria and received trials of tricyclic antidepressants , antipsychotics , the combination of the two , electroconvulsive therapy , or placebo and psychotherapy . Only three of 18 psychotic patients vs. 17 of 23 nonpsychotic patients responded to antidepressants alone . Electroconvulsive therapy and the combination of antipsychotic and antidepressant medication gave better responses . These data suggest that major depressive disorder with psychotic features is best considered as a distinct subtype rather than a severe variant of major depression OBJECTIVE The study explored the phenomenology and prognostic significance of delusions in major depressive disorder . METHOD From 452 patients with DSM-III major depression , we selected those with at least one belief fulfilling both DSM-III prerequisites for a delusion ( i.e. , being of " delusional proportions " and being maintained with " delusional intensity " ) . These patients were compared to the others with respect to demographic , historical , and index episode features ; time spent in a depressive episode during a prospect i ve observation period ; and 10-year outcome . The same comparisons were made between patients with mood-incongruent delusions and those with mood-congruent delusions only . The study covered the period between January 1 , 1978 , and December 31 , 2005 . RESULTS About 20 % of patients had at least one delusion in their index episode . An additional 5.3 % had a belief fulfilling only one of the DSM-III prerequisites for a delusion . In about one quarter of delusional patients , the index episode was not " severe . " Almost 10 % of delusional patients had both mood-congruent and mood-incongruent delusions . In patients with delusions , time to syndromal recovery from index episode was longer and antipsychotic medication was more frequently used ( both p < .0001 ) . The presence of delusions predicted a higher depressive morbidity during the prospect i ve observation period ( p < .05 ) , but not a poorer 10-year outcome . No variable discriminated patients with mood-incongruent delusions from those with mood-congruent delusions only . CONCLUSION The presence of delusions in a major depressive episode has significant therape Output:	Our meta- analysis may provide evidence that the presence of psychosis increases the risk of suicide in patients suffering from severe depression . Conclusions The presence of psychosis in major depression should alert clinicians for the increased risk of completed suicide .
MS2958	*TASK* the task is to summarize an input biomedical literature in six sentences *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 phase III r and omized trial was conducted to investigate whether induction chemotherapy followed by radiation can influence survival as compared with radiation alone in unresectable , locally advanced non-small-cell lung cancer ( LADNSCLC ) . A total of 101 patients with unresectable stage IIIA or IIIB NSCLC were enrolled . Patients were stratified by performance status , weight loss , histology and stage , and then r and omized to receive combined chemoradiotherapy or radiotherapy alone . Radiotherapy was administered in 1.8 Gy to 2.0 Gy st and ard fractions daily 5 times weekly for a total dose of 60 Gy to 65 Gy . The combined group received induction of cisplatin , etoposide , and vinblastine ( PEV ) chemotherapy with cisplatin 20 mg/m2 on days 1 to 5 , etoposide 100 mg/m2 on days 2 to 4 , and vinblastine 6 mg/m2 on day 1 , which wasrepeated every 3 weeks for 3 courses , after which time the patients underwent radiotherapy . Of 101 patients registered , 89 patients ( 43 combined , 46 radiotherapy alone ) were eligible for analysis . The response rates for the combined and radiotherapy groups were 65 % ( 28/43 ) and 70 % ( 32/46 ) , respectively . The median survival time ( MST ) showed a tendency to be more prolonged in the combined group than in the group receiving radiotherapy alone ( 13.8 vs. 8.5 months ) . The MST in patients with nonsquamous histology was strikingly prolonged in the combined group as compared with the radiotherapy group ( 14 vs. 3.6 months , p 0.027 ) . Likewise , the MST in patients with stage IIIB was significantly prolonged in the combined group as compared with the radiotherapy group ( 11.1 vs. 7.2 months , p 0.045 ) . Together , the MST of the high-risk group with nonsquamous or stage IIIB was significantly higher in the combined group than that seen in the radiotherapy group ( 11.6 vs. 8 months , p 0.046 ) , whereas the MST of the low-risk group , defined as having both squamous histology and stage IIIA , was similar in the two treatment groups ( 18.3 vs. 20.8 months , p = 0.293 ) . In conclusion , induction PEV chemotherapy plus radiotherapy is superior to radiotherapy alone in high-risk subsets of unresectable LAD-NSCLC and therapeutic strategy should be based on the identification of prognostic factors Background Gefitinib is an oral EGFR tyrosine kinase inhibitors which may act as a radiosensitizer . Patients and Methods This phase II study evaluated the efficacy of gefitinib 250 mg once daily in combination with thoracic radiotherapy ( 66 Gy in 6.5 weeks , 2 Gy/day , 5 fractions/week ) followed by consolidation chemotherapy ( IV cisplatin and vinorelbine ) as first line treatment in a population of unselected stage IIIB NSCLC patients according to EGFR mutation status . Results Due to a low accrual rate in this study , the sample size ( n = 50 ) was not reached . Sixteen patients were included in four centers , 50 % had adenocarcinoma and 75 % were male . Genomic alterations ( 7 patients studied ) retrieved TP53 mutation in 2 patients and no EGFR mutation . Four weeks after radiotherapy , 3 patients ( 19 % ) had a partial response , 6 ( 38 % ) had a stable disease , and 7 had a progression ( 44 % ) . Median overall survival was 11 months and median progression-free survival was 5 months . At the time of the last contact , 5 patients ( 31 % ) were still alive . Main toxicities were gastrointestinal ( 81 % ) , cutaneous ( 81 % ) , general ( 56 % ) , and respiratory ( 50 % ) . There were 12>G3 adverse events in 7 ( 47 % ) patients , and there was one toxic-death during the concomitant period due to an interstitial pneumonitis . There were two possible adverse events-related deaths during the chemotherapy period ( pulmonary embolism ( n = 1 ) and sudden death after the administration of the 3rd course of chemotherapy ( n = 1 ) ) . Conclusion The benefit of Gefitinib-RT could not be confirmed due to premature trial discontinuation . Further evaluation is required , especially in patients with EGFR mutated NSCLC BACKGROUND The efficacy of the ALK inhibitor crizotinib as compared with st and ard chemotherapy as first-line treatment for advanced ALK-positive non-small-cell lung cancer ( NSCLC ) is unknown . METHODS We conducted an open-label , phase 3 trial comparing crizotinib with chemotherapy in 343 patients with advanced ALK-positive nonsquamous NSCLC who had received no previous systemic treatment for advanced disease . Patients were r and omly assigned to receive oral crizotinib at a dose of 250 mg twice daily or to receive intravenous chemotherapy ( pemetrexed , 500 mg per square meter of body-surface area , plus either cisplatin , 75 mg per square meter , or carboplatin , target area under the curve of 5 to 6 mg per milliliter per minute ) every 3 weeks for up to six cycles . Crossover to crizotinib treatment after disease progression was permitted for patients receiving chemotherapy . The primary end point was progression-free survival as assessed by independent radiologic review . RESULTS Progression-free survival was significantly longer with crizotinib than with chemotherapy ( median , 10.9 months vs. 7.0 months ; hazard ratio for progression or death with crizotinib , 0.45 ; 95 % confidence interval [ CI ] , 0.35 to 0.60 ; P<0.001 ) . Objective response rates were 74 % and 45 % , respectively ( P<0.001 ) . Median overall survival was not reached in either group ( hazard ratio for death with crizotinib , 0.82 ; 95 % CI , 0.54 to 1.26 ; P=0.36 ) ; the probability of 1-year survival was 84 % with crizotinib and 79 % with chemotherapy . The most common adverse events with crizotinib were vision disorders , diarrhea , nausea , and edema , and the most common events with chemotherapy were nausea , fatigue , vomiting , and decreased appetite . As compared with chemotherapy , crizotinib was associated with greater reduction in lung cancer symptoms and greater improvement in quality of life . CONCLUSIONS Crizotinib was superior to st and ard first-line pemetrexed-plus-platinum chemotherapy in patients with previously untreated advanced ALK-positive NSCLC . ( Funded by Pfizer ; PROFILE 1014 Clinical Trials.gov number , NCT01154140 . ) BACKGROUND Activating mutations in EGFR are important markers of response to tyrosine kinase inhibitor ( TKI ) therapy in non-small-cell lung cancer ( NSCLC ) . The OPTIMAL study compared efficacy and tolerability of the TKI erlotinib versus st and ard chemotherapy in the first-line treatment of patients with advanced EGFR mutation-positive NSCLC . METHODS We undertook an open-label , r and omised , phase 3 trial at 22 centres in China . Patients older than 18 years with histologically confirmed stage IIIB or IV NSCLC and a confirmed activating mutation of EGFR ( exon 19 deletion or exon 21 L858R point mutation ) received either oral erlotinib ( 150 mg/day ) until disease progression or unacceptable toxic effects , or up to four cycles of gemcitabine plus carboplatin . Patients were r and omly assigned ( 1:1 ) with a minimisation procedure and were stratified according to EGFR mutation type , histological subtype ( adenocarcinoma vs non-adenocarcinoma ) , and smoking status . The primary outcome was progression-free survival , analysed in patients with confirmed disease who received at least one dose of study treatment . The trial is registered at Clinical Trials.gov , number NCT00874419 , and has completed enrolment ; patients are still in follow-up . FINDINGS 83 patients were r and omly assigned to receive erlotinib and 82 to receive gemcitabine plus carboplatin ; 82 in the erlotinib group and 72 in the chemotherapy group were included in analysis of the primary endpoint . Median progression-free survival was significantly longer in erlotinib-treated patients than in those on chemotherapy ( 13.1 [ 95 % CI 10.58 - 16.53 ] vs 4.6 [ 4.21 - 5.42 ] months ; hazard ratio 0.16 , 95 % CI 0.10 - 0.26 ; p<0.0001 ) . Chemotherapy was associated with more grade 3 or 4 toxic effects than was erlotinib ( including neutropenia in 30 [ 42 % ] of 72 patients and thrombocytopenia in 29 [ 40 % ] patients on chemotherapy vs no patients with either event on erlotinib ) ; the most common grade 3 or 4 toxic effects with erlotinib were increased alanine aminotransferase concentrations ( three [ 4 % ] of 83 patients ) and skin rash ( two [ 2 % ] patients ) . Chemotherapy was also associated with increased treatment-related serious adverse events ( ten [ 14 % ] of 72 patients [ decreased platelet count , n=8 ; decreased neutrophil count , n=1 ; hepatic dysfunction , n=1 ] vs two [ 2 % ] of 83 patients [ both hepatic dysfunction ] ) . INTERPRETATION Compared with st and ard chemotherapy , erlotinib conferred a significant progression-free survival benefit in patients with advanced EGFR mutation-positive NSCLC and was associated with more favourable tolerability . These findings suggest that erlotinib is important for first-line treatment of patients with advanced EGFR mutation-positive NSCLC . FUNDING F Hoffmann-La Roche Ltd ( China ) ; Science and Technology Commission of Shanghai Municipality Purpose Concurrent chemoradiotherapy ( CCRT ) is the st and ard care for stage III non-small cell lung cancer ( NSCLC ) patients ; however , a more effective regimen is needed to improve the outcome by better controlling occult metastases . We conducted two parallel r and omized phase II studies to incorporate erlotinib or irinotecan-cisplatin ( IP ) into CCRT for stage III NSCLC depending on epidermal growth factor receptor ( EGFR ) mutation status . Material s and Methods Patients with EGFR-mutant tumors were r and omized to receive three cycles of erlotinib first and then either CCRT with erlotinib followed by erlotinib ( arm A ) or CCRT with IP only ( arm B ) . Patients with EGFR unknown or wild-type tumors were r and omized to receive either three cycles of IP before ( arm C ) or after CCRT with IP ( arm D ) . Results Seventy-three patients were screened and the study was closed early because of slow accrual after 59 patients were r and omized . Overall , there were seven patients in arm A , five in arm B , 22 in arm C , and 25 in arm D. The response rate was 71.4 % and 80.0 % for arm A and B , and 70.0 % and 73.9 % for arm C and D. The median overall survival ( OS ) was 39.3 months versus 31.2 months for arm A and B ( p=0.442 ) , and 16.3 months versus 25.3 months for arm C and D ( p=0.050 ) . Patients with sensitive EGFR mutations had significantly longer OS than EGFR-wild patients ( 74.8 months vs. 25.3 months , p=0.034 ) . There were no unexpected toxicities . Conclusion Combined-modality treatment by molecular diagnostics is feasible in stage III NSCLC . EGFR-mutant patients appear to be a distinct subset with longer survival Background Concurrent chemoradiotherapy is the st and ard of care for inoperable stage III non-small cell lung cancer ( NSCLC ) for patients who can tolerate it . We explored if adding erlotinib would increase the effectiveness of chemoradiotherapy without increasing toxicity in a single-arm prospect i ve phase II trial . Methods Forty-eight patients with previously untreated NSCLC received intensity-modulated radiation therapy ( 63 Gy/35 fractions ) on Monday – Friday , with chemotherapy ( paclitaxel 45 mg/m2 , carboplatin AUC=2 ) on Mondays , for 7 weeks . All patients also received the epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitor erlotinib ( 150 mg orally 1/day ) on Tuesday – Sunday for 7 weeks followed by consolidation paclitaxel – carboplatin . The primary endpoint was time to progression ; secondary endpoints were overall survival ( OS ) , toxicity , response , and disease control and whether any endpoint differed by EGFR mutation status . Results Of 46 patients evaluable for response , 40 were former or never-smokers and 41 were evaluable for EGFR mutations ( 37 wild-type [ wt ] and 4 [ mutated ; all Output:	There is evidence , albeit of low quality , that added the TKIs to TRT or CRT may improve RR and survival outcomes in patients with EGFR mutant status unknown advanced or metastatic NSCLC relative to other studies of TKIs alone , TRT alone or CRT
MS2959	*TASK* the task is to summarize an input biomedical literature in six sentences *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 characterized BRCA1 and BRCA2 status ( mutation/methylation ) in a consecutive series of cases of ovarian carcinoma in order to identify differences in clinicopathological features , molecular characteristics , and outcome between the pelvic high- grade serous cancers with ( i ) germline or somatic mutations in BRCA1 or BRCA2 , ( ii ) methylation of BRCA1 , and ( iii ) normal BRCA1 or BRCA2 . In all , 131 women were identified prospect ively , who were undergoing surgical staging and agreed to germline testing for BRCA1 and BRCA2 mutations . Histopathology , germline and somatic BRCA1 or BRCA2 mutations , BRCA1 methylation , and BRCA1 and BRCA2 mRNA expression levels distinguished four subgroups . In all , 103 cases were high- grade serous carcinoma and of these 31 ( 30 % ) had germline or somatic BRCA1 or BRCA2 mutations ( 20 % BRCA1 and 10 % BRCA2 ) ( group 1 ) , 21 ( 20 % ) had methylation of BRCA1 ( group 2 ) , and in 51 ( 50 % ) there was no BRCA loss ( group 3 ) . Group 4 consisted of 28 cases of non-high- grade serous , none of which had BRCA loss . BRCA1 and BRCA2 mRNA expression levels correlated with design ated group ( P=0.0008 ) . Among high- grade serous carcinomas , there were no differences between groups 1–3 with respect to stage , ascites , CA125 level , platinum sensitivity , cytoreduction rate , neoadjuvant chemotherapy , or survival . Tumors with BRCA1 or BRCA2 mutations had increased immune infiltrates ( CD20 and TIA-1 ) compared with high- grade serous without mutations ( P=0.034 , 0.027 ) . TP53 expression differed between groups ( P<0.0001 ) , with abnormal TP53 expression in 49/50 tumors from groups 1 and 2 . Wild-type TP53 expression was associated with worse outcome in high- grade serous ( P<0.001 ) . BRCA loss ( mutation/methylation ) is a common event in the pelvic high- grade serous ( 50 % ) . TP53 abnormalities and increased immune cell infiltrates are significantly more common in high- grade serous with germline and somatic mutations in BRCA1 or BRCA2 , compared with tumors lacking BRCA abnormalities This multi-centre UK study assesses the impact of predictive testing for breast and ovarian cancer predisposition genes ( BRCA1/2 ) in the clinical context . In the year following predictive testing , 261 adults ( 59 male ) from nine UK genetics centres participated ; 91 gene mutation carriers and 170 noncarriers . Self-report question naires were completed at baseline ( pre-genetic testing ) and 1 , 4 and 12 months following the genetic test result . Men were assessed for general mental health ( by general health question naire ( GHQ ) ) and women for general mental health , cancer-related worry , intrusive and avoidant thoughts , perception of risk and risk management behaviour . Main comparisons were between female carriers and noncarriers on all measures and men and women for general mental health . Female noncarriers benefited psychologically , with significant reductions in cancer-related worry following testing ( P<0.001 ) . However , younger female carriers ( < 50 years ) showed a rise in cancer-related worry 1 month post-testing ( P<0.05 ) . This returned to pre-testing baseline levels 12 months later , but worry remained significantly higher than noncarriers throughout ( P<0.01 ) . There were no significant differences in GHQ scores between males and females ( both carriers and noncarriers ) at any time point . Female carriers engaged in significantly more risk management strategies than noncarriers in the year following testing ( e.g. mammograms ; 92 % carriers vs 30 % noncarriers ) . In the 12 months post-testing , 28 % carriers had bilateral risk-reducing mastectomy and 31 % oophorectomy . Oophorectomy was confined to older ( mean 41 yrs ) women who already had children . However , worry about cancer was not assuaged by surgery following genetic testing , and this requires further investigation . In all , 20 % of female carriers reported insurance problems . The data show persistent worry in younger female gene carriers and confirm changes in risk management consistent with carrier status . Men were not adversely affected by genetic testing in terms of their general mental health This prospect i ve multicentre study assesses long-term impact of genetic testing for breast/ovarian cancer predisposition in a clinical cohort . Areas evaluated include risk management , distress and insurance problems 3 years post-testing . Participants are adults unaffected with cancer from families with a known BRCA1/2 mutation . One hundred and ninety-three out of 285 ( 70 % response ) participants at nine UK clinical genetics centres completed assessment s at 3 years : 80 % female ; 37 % carriers of a BRCA1/2 mutation . In the 3 years , post-genetic testing carriers reported more risk management activities than non-carriers . Fifty-five per cent of female carriers opted for risk reducing surgery ; 43 % oophorectomy ; and 34 % mastectomy . Eighty-nine per cent had mammograms compared with 47 % non-carriers . Thirty-six per cent non-carriers ⩾50 years did not have a mammogram post-test . Twenty-two per cent male carriers had colorectal and 44 % prostate screening compared with 5 and 19 % non-carriers respectively . Seven per cent carriers and 1 % non-carriers developed cancer . Distress levels did not differ in carriers and non-carriers at 3-year follow-up . Forty per cent of female carriers reported difficulties with life and /or health insurance . Given the return to pre-test levels of concern among female non-carriers at 3 years and a substantial minority not engaging in recommended screening , there appears to be a need to help some women underst and the meaning of their genetic status Objective Opportunistic bilateral salpingectomy is now promoted for women at the time of hysterectomy for a benign disease , consequent to the fimbrial end of the fallopian tube emerging as the primary site for carcinogenesis in high- grade serous carcinomas . In high-risk women with an identified germ line mutation , bilateral salpingo-oophorectomy offers the greatest risk reduction for ovarian cancer . Currently , no prospect i ve evidence exists with respect to the effectiveness of opportunistic salpingectomy alone in preventing ovarian cancer . Although it is thought that there is no direct connection between the ovary and its adjacent fallopian tube , we often find remnants of the fimbria adherent to the ovary at the time of surgery . If this tubo-ovarian interface is not separate , then practice s such as salpingectomy and radical fimbriectomy may be incomplete , and the effectiveness of this technique as a prophylactic strategy may need reconsideration . We aim ed to establish whether there might exist a direct attachment of the fimbria to the ovary by examining this interface in surgically removed specimens . Methods The tubes and ovaries of 20 women undergoing risk-reducing salpingo-oophorectomy were examined using the Sectioning and Extensively Examining the Fimbriated End of the Tubes protocol and p53 immunohistochemistry for lesions suspicious of serous intraepithelial tubal carcinoma . Results Three specimens showed fimbria adherent to the ovary at the histopathological analysis . One p53 signature was identified , but there were no occult cancers or serous intraepithelial tubal carcinomas . Conclusions Although only a small study , the findings show that microscopic fimbriae are adherent to the ovary . This relationship challenges the recommendation for bilateral salpingectomy alone for risk-reducing surgery because the primary site of carcinogenesis may be left on the ovary to later develop into a high- grade serous carcinoma . A larger study is needed to assess our findings related to the tubo-ovarian interface and its implication s for long-term ovarian cancer development . Until then , caution on using this technique alone in the high-risk patient should be adopted OBJECTIVES Considerable morbidity persists among survivors of breast cancer ( BC ) including high levels of psychological stress , anxiety , depression , fear of recurrence , and physical symptoms including pain , fatigue , and sleep disturbances , and impaired quality of life . Effective interventions are needed during this difficult transitional period . METHODS We conducted a r and omized controlled trial of 84 female BC survivors ( Stages 0-III ) recruited from the H. Lee Moffitt Cancer and Research Institute . All subjects were within 18 months of treatment completion with surgery and adjuvant radiation and /or chemotherapy . Subjects were r and omly assigned to a 6-week Mindfulness-Based Stress Reduction ( MBSR ) program design ed to self-regulate arousal to stressful circumstances or symptoms ( n=41 ) or to usual care ( n=43 ) . Outcome measures compared at 6 weeks by r and om assignment included vali date d measures of psychological status ( depression , anxiety , perceived stress , fear of recurrence , optimism , social support ) and psychological and physical subscales of quality of life ( SF-36 ) . RESULTS Compared with usual care , subjects assigned to MBSR(BC ) had significantly lower ( two-sided p<0.05 ) adjusted mean levels of depression ( 6.3 vs 9.6 ) , anxiety ( 28.3 vs 33.0 ) , and fear of recurrence ( 9.3 vs 11.6 ) at 6 weeks , along with higher energy ( 53.5 vs 49.2 ) , physical functioning ( 50.1 vs 47.0 ) , and physical role functioning ( 49.1 vs 42.8 ) . In stratified analyses , subjects more compliant with MBSR tended to experience greater improvements in measures of energy and physical functioning . CONCLUSIONS Among BC survivors within 18 months of treatment completion , a 6-week MBSR(BC ) program result ed in significant improvements in psychological status and quality of life compared with usual care BACKGROUND Reliable estimates of cancer risk are critical for guiding management of BRCA1 and BRCA2 mutation carriers . The aims of this study were to derive penetrance estimates for breast cancer , ovarian cancer , and contralateral breast cancer in a prospect i ve series of mutation carriers and to assess how these risks are modified by common breast cancer susceptibility alleles . METHODS Prospect i ve cancer risks were estimated using a cohort of 978 BRCA1 and 909 BRCA2 carriers from the United Kingdom . Nine hundred eighty-eight women had no breast or ovarian cancer diagnosis at baseline , 1509 women were unaffected by ovarian cancer , and 651 had been diagnosed with unilateral breast cancer . Cumulative risks were obtained using Kaplan-Meier estimates . Associations between cancer risk and covariables of interest were evaluated using Cox regression . All statistical tests were two-sided . RESULTS The average cumulative risks by age 70 years for BRCA1 carriers were estimated to be 60 % ( 95 % confidence interval [ CI ] = 44 % to 75 % ) for breast cancer , 59 % ( 95 % CI = 43 % to 76 % ) for ovarian cancer , and 83 % ( 95 % CI = 69 % to 94 % ) for contralateral breast cancer . For BRCA2 carriers , the corresponding risks were 55 % ( 95 % CI = 41 % to 70 % ) for breast cancer , 16.5 % ( 95 % CI = 7.5 % to 34 % ) for ovarian cancer , and 62 % ( 95 % CI = 44 % to 79.5 % ) for contralateral breast cancer . BRCA2 carriers in the highest tertile of risk , defined by the joint genotype distribution of seven single nucleotide polymorphisms associated with breast cancer risk , were at statistically significantly higher risk of developing breast cancer than those in the lowest tertile ( hazard ratio = 4.1 , 95 % CI = 1.2 to 14.5 ; P = .02 ) . CONCLUSIONS Prospect i ve risk estimates confirm that BRCA1 and BRCA2 carriers are at high risk of developing breast , ovarian , and contralateral breast cancer . Our results confirm findings from retrospective studies that common breast cancer susceptibility alleles in combination are predictive of breast cancer risk for BRCA2 carriers Purpose : To investigate the medical and psychosocial factors determining the time to prophylactic surgery of unaffected women carriers of a deleterious BRCA1/2 mutation . Methods : Prospect i ve study on a French national cohort of unaffected BRCA1/2 carriers ( N = 244 ) ; multivariate Cox proportional hazard modeling . Results : Median follow-up time was 2.33 years ( range , 0.04–6.84 years ) . Time to surgery was shorter when the psychological impact of BRCA1/2 result disclosure was stated to be higher ( P ≤ 0.01 ) . Those who intended to opt for prophylactic surgery before being tested did so faster and more frequently after test disclosure than those who were undecided/opposed . The older the women were , the faster their uptake of risk-reducing salpingo-oophorectomy ( adjusted hazard ratio > 2.95 ; P < 0.001 ) was ; the uptake of those with at least two children was also faster ( adjusted hazard ratio = 2 Output:	Other outcome measures on the Female Sexual Function Index and the Female Sexual Distress Scale showed no significant differences between the two groups .
MS2960	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Patients with chalazia were r and omly allocated to treatment by intralesional triamcinolone injection or incision and curettage . Incision and curettage result ed in a significantly higher rate of resolution by two weeks after treatment OBJECTIVE The research ers sought to assess whether the widely used 1994 Cochrane Highly Sensitive Search Strategy ( HSSS ) for r and omized controlled trials ( RCTs ) in MEDLINE could be improved in terms of sensitivity , precision , or parsimony . METHODS A gold st and ard of 1,347 RCT records and a comparison group of 2,400 non-trials were r and omly selected from MEDLINE . Terms occurring in at least 1 % of RCT records were identified . Fifty percent of the RCT and comparison group records were r and omly selected , and the ability of the terms to discriminate RCTs from non-trial records was determined using logistic regression . The best performing combinations of terms were tested on the remaining records and in MEDLINE . RESULTS The best discriminating term was " Clinical Trial " ( Publication Type ) . In years where the Cochrane assessment of MEDLINE records had taken place , the strategies identified few additional unindexed records of trials . In years where Cochrane assessment has yet to take place , " R and omized Controlled Trial " ( Publication Type ) proved highly sensitive and precise . Adding six more search terms identified further , unindexed trials at reasonable levels of precision and with sensitivity almost equal to the Cochrane HSSS . CONCLUSIONS Most reports of RCTs in MEDLINE can now be identified easily using " R and omized Controlled Trial " ( Publication Type ) . More sensitive search es can be achieved by a brief strategy , the Centre for Review s and Dissemination/Cochrane Highly Sensitive Search Strategy ( 2005 revision ) We evaluated the safety and efficacy of tobramycin and gentamicin sulfate ophthalmic solutions in the treatment of patients with bacterial infections of the conjunctivas . In this double-masked study involving 66 patients , the two aminoglycosides were found to be equally safe and effective , although the in vitro data suggested that tobramycin may be more efficacious against Pseudomonas infections . Staphylococcus aureus and S. epidermidis were the most frequent isolates from the infected eyes ( 59.8 % and 20.6 % , respectively ) The presented pilot study compared the effectiveness of combined antibiotic ophthalmic solution ( neomycin sulfate , polymyxin B sulfate and gramicidin ) with a placebo ( artificial tear ) in the treatment of hordeolum after incision and curettage ( I&C ) . A r and omized , placebo-controlled trial with patients and investigators blinded from the start started from June 2002 to May 2003 . Subjects were patients with untreated hordeolum who subsequently underwent I&C at the Ophthalmology Department . The patients were r and omized into 2 groups : group A for combined antibiotic ophthalmic solution , and group B for artificial tear containing the antibiotic solution base . Pain score , mass size and duration of cure were recorded before and on the 3rd and 7th day after treatment . The study included 14 patients in each group . Two subjects in group A and three subjects in group B dropped out . There were no statistically significant differences of all outcomes in both groups , even with the intention-to-treat analysis . The conclusion is combined antibiotic ophthalmic solution is not more effective than placebo in the treatment of hordeolum after Background Loteprednol etabonate 0.5 % and tobramycin 0.3 % ophthalmic suspension ( LE/T ) is indicated for steroid-responsive inflammatory ocular conditions where superficial bacterial ocular infection or a risk of bacterial ocular infection exists . LE/T was shown to be safe in healthy volunteers and patients aged 18 years and older with minimal effect on intraocular pressure ( IOP ) . Objective The aim of the study was to evaluate the safety of LE/T in pediatric subjects by examining data from two clinical studies . Methods Two r and omized , multicenter , double-masked , parallel-group ( one two-arm , the other four-arm ) studies were conducted in subjects aged 0–6 years ( N = 245 ) . One study assessed LE/T compared with vehicle in the management of lid inflammation ( n = 108 ) and the other compared LE/T with loteprednol etabonate ophthalmic suspension 0.5 % ( LE ) , tobramycin ophthalmic solution 0.3 % ( tobramycin ) , and vehicle in the treatment of blepharoconjunctivitis ( n = 137 ) . In the first study , subjects were r and omized to LE/T or vehicle administered four times daily ( qid ) for the first 7 days followed by twice daily ( bid ) for 7 days along with warm compresses bid for the entire 2 weeks . In the second study , subjects were r and omized to LE/T , LE , tobramycin , or vehicle administered qid for 14 days . Treatment-emergent ocular and non-ocular adverse events ( AEs ) and bilateral vision were assessed at all study visits in both studies . In addition , in the lid inflammation study , IOP was assessed at all visits . The primary safety endpoint in both studies was the incidence of treatment-emergent AEs . Results The incidence of LE/T treatment-emergent AEs was low . A total of four ocular AEs were reported for three LE/T-treated subjects in the first study ( conjunctivitis [ two events ] , meibomian gl and dysfunction , and corneal staining ) , and one ocular AE was reported for an LE/T-treated subject in the second study ( eye pain ) . A total of 13 non-ocular AEs were reported for eight LE/T-treated subjects in the two trials . The most prevalent non-ocular AEs were pyrexia ( three events ) and rash ( two events ) . There were no differences in the incidence of specific ocular and non-ocular AEs between the LE/T group and the comparator treatment group . In both studies , there were no clinical ly meaningful reductions in vision at follow-up visits . Mean IOP and IOP changes from baseline , assessed in the lid inflammation study , were not different between LE/T and vehicle treatment groups at any study visits . Conclusion The results of these two clinical trials demonstrate the short-term safety of treatment with topical LE/T in pediatric subjects ( 0–6 years of age ) with lid inflammation or blepharoconjunctivitis We tested an over-the-counter ophthalmic ointment , yellow mercuric oxide 1 % , for safety and efficacy in decreasing eyelid-margin bacterial-colony counts . Of 150 patients screened for high bacterial levels , 78 were r and omized in double-blind fashion to either yellow mercuric oxide bid ( 41 patients or 53 % ) or a placebo ( 37 patients or 47 % ) . Bacterial-colony counts were determined at outset and at days 4 and 7 of treatment . At the conclusion of treatment on day 7 , 87 % of patients in the mercuric oxide group were successful in decreasing bacterial counts , compared with 59 % of patients treated with placebo ( P = .01 ) . Side effects were no higher in the active group than in the placebo group . We have shown mercuric oxide 1 % to be safe and effective in reducing eyelid bacterial-colony counts in patients with hordeolum and blepharitis A trial was conducted to compare the efficacy of the treatment of chalazions by injection of triamcinolone acetonide with conventional incision and curettage . Of the 39 injected cases 77 % resolved completely , though 54 % of the injected cases required a second injection . Of the 30 surgically treated cases 90 % resolved , but 27 % required a second operation . Injection of chalazions with a steroid suspension is a convenient and reasonably effective alternative to the st and ard surgical management of this common condition Output:	We did not find any evidence for or against the effectiveness of non-surgical interventions for the treatment of an internal hordeolum .
MS2961	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Efficacy trials suggest that structured psychological therapies may significantly reduce recurrence rates of major mood episodes in individuals with bipolar disorders . AIMS To compare the effectiveness of treatment as usual with an additional 22 sessions of cognitive-behavioural therapy ( CBT ) . METHOD We undertook a multicentre , pragmatic , r and omised controlled treatment trial ( n=253 ) . Patients were assessed every 8 weeks for 18 months . RESULTS More than half of the patients had a recurrence by 18 months , with no significant differences between groups ( hazard ratio=1.05 ; 95 % CI 0.74 - 1.50 ) . Post hoc analysis demonstrated a significant interaction ( P=0.04 ) such that adjunctive CBT was significantly more effective than treatment as usual in those with fewer than 12 previous episodes , but less effective in those with more episodes . CONCLUSIONS People with bipolar disorder and comparatively fewer previous mood episodes may benefit from CBT . However , such cases form the minority of those receiving mental healthcare BACKGROUND The efficacy and effectiveness of cognitive therapy ( CT ) is well established for unipolar disorders , but little is known about its utility in bipolar disorders . This study aim ed to explore the feasibility and efficacy of using CT as an adjunct to usual psychiatric treatment in this patient population . METHOD Subjects referred by general adult psychiatrists were assessed by and independent rater and then r and omly allocated to immediate CT ( N = 21 ) or 6-month waiting-list control , which was then followed by CT ( N = 21 ) . Observer and self-ratings of symptoms and functioning were undertaken immediately prior to CT , after a 6-month course of CT and a further 6-months later . Data on relapse and hospitalization rates in the 18 months before and after commencing CT were also collected . RESULTS At 6-month follow-up , subjects allocated to CT showed statistically significantly greater improvements in symptoms and functioning as measured on the Beck Depression Inventory , the Internal State Scale , and the Global Assessment of Functioning than those in the waiting-list control group . In the 29 patients who eventually received CT , relapse rates in the 1 8 months after commencing CT showed a 60 % reduction in comparison with the 18 months prior to commencing CT . Seventy per cent of subjects who commenced therapy viewed CT as highly acceptable . CONCLUSION Although the results of this study are encouraging , the use of CT in subjects with bipolar disorders is more complex than in unipolar disorders and requires a high level of therapist expertise . The therapy may prove to be particularly useful in the treatment of bipolar depression Recently hospitalized bipolar , manic patients ( N = 53 ) were r and omly assigned to a 9-month , manual-based , family-focused psychoeducational therapy ( n = 28 ) or to an individually focused patient treatment ( n = 25 ) . All patients received concurrent treatment with mood-stabilizing medications . Structured follow-up assessment s were conducted at 3-month intervals for a 1-year period ofactive treatment and a 1-year period of posttreatment follow-up . Compared with patients in individual therapy , those in family-focused treatment were less likely to be rehospitalized during the 2-year study period . Patients in family treatment also experienced fewer mood disorder relapses over the 2 years , although they did not differ from patients in individual treatment in their likelihood of a first relapse . Results suggest that family psychoeducational treatment is a useful adjunct to pharmacotherapy in decreasing the risk of relapse and hospitalization frequently associated with bipolar disorder Abstract Objective : To determine the efficacy of teaching patients with bipolar disorder ( manic-depressive psychosis ) to identify early symptoms of relapse and seek prompt treatment from health services . Design : Single blind r and omised controlled trial with matching on four baseline variables using a minimisation algorithm . Setting : Mental health services in four NHS trusts ( one teaching , three non-teaching ) . Subjects : 69 patients with bipolar disorder who had had a relapse in the previous 12 months . Interventions : Seven to 12individual treatment sessions from a research psychologist plus routine care or routine care alone . Main outcome measures : Time to first manic or depressive relapse , number of manic or depressive relapses , and social functioning examined by st and ardised interviews every six months for 18 months . Results : 25th centile time to first manic relapse in experimental group was 65weeks compared with 17weeks in the control group . Event curves of time to first manic relapse significantly differed between experimental and control groups ( log rank 7.04 , df=1 , P=0.008 ) , with significant reductions in the number of manic relapses over 18months ( median difference 30 % ( 95 % confidence interval 8 % to 52 % ) , P=0.013 ) . The experimental treatment had no effect on time to first relapse or number of relapses with depression , but it significantly improved overall social functioning ( mean difference 2.0(0.7to 3.2 ) , P=0.003 ) and employment ( mean difference 0.7(0.1to 1.3 ) , P=0.030 ) by 18months . Conclusion : Teaching patients to recognise early symptoms of manic relapse and seek early treatment is associated with important clinical improvements in time to first manic relapse , social functioning , and employment BACKGROUND Despite the availability of efficacious medications and psychotherapies , care of bipolar disorder in everyday practice is often deficient . This trial evaluated the effectiveness of a multi-component care management program in a population -based sample of people with bipolar disorder . METHOD Four hundred and forty-one patients treated for bipolar disorder during the prior year were r and omly assigned to continued usual care or usual care plus a systematic care management program including : initial assessment and care planning , monthly telephone monitoring including brief symptom assessment and medication monitoring , feedback to and coordination with the mental health treatment team , and a structured group psychoeducational program -- all provided by a nurse care manager . Blinded quarterly assessment s generated week-by-week ratings of severity of depression and mania symptoms using the Longitudinal Interval Follow-Up Evaluation . RESULTS Participants assigned to the intervention group had significantly lower mean mania ratings averaged across the 12-month follow-up period ( Z= 2.44 , p=0.015 ) and approximately one-third less time in hypomanic or manic episode ( 2.59 weeks v. 1.69 weeks ) . Mean depression ratings across the entire follow-up period did not differ significantly between the two groups , but the intervention group showed a greater decline in depression ratings over time ( Z statistic for group-by-time interaction = 1.98 , p = 0.048 ) . CONCLUSIONS A systematic care program for bipolar disorder significantly reduces risk of mania over 12 months . Preliminary results suggest a growing effect on depression over time , but longer follow-up will be needed BACKGROUND The authors ' goal was to pilot test a newly developed manual-based group psychotherapy , called Integrated Group Therapy ( IGT ) , for patients with bipolar disorder and substance dependence . METHOD In this open trial , patients with DSM-IV bipolar disorder and substance dependence ( N = 45 ) were recruited in sequential blocks to receive either group therapy ( N = 21 ) or 6 monthly assessment s , but no experimental treatment ( N = 24 ) . RESULTS When compared with patients who did not receive group therapy , patients who received IGT had significantly better outcomes on the Addiction Severity Index drug composite score ( p < .03 ) , percentage of months abstinent ( p < .01 ) , and likelihood of achieving 2 ( p < .002 ) or 3 ( p < .004 ) consecutive abstinent months . CONCLUSION IGT is a promising treatment for patients with bipolar disorder and substance dependence , who have traditionally had poor outcomes . It is unclear , however , how much of the improvement among the group therapy patients is attributable to the specific content of the treatment . A study comparing this treatment with another active psychotherapy treatment is warranted CONTEXT Psychosocial interventions have been shown to enhance pharmacotherapy outcomes in bipolar disorder . OBJECTIVE To examine the benefits of 4 disorder-specific psychotherapies in conjunction with pharmacotherapy on time to recovery and the likelihood of remaining well after an episode of bipolar depression . DESIGN R and omized controlled trial . SETTING Fifteen clinics affiliated with the Systematic Treatment Enhancement Program for Bipolar Disorder . Patients A total of 293 referred out patients with bipolar I or II disorder and depression treated with protocol pharmacotherapy were r and omly assigned to intensive psychotherapy ( n = 163 ) or collaborative care ( n = 130 ) , a brief psychoeducational intervention . INTERVENTIONS Intensive psychotherapy was given weekly and biweekly for up to 30 sessions in 9 months according to protocol s for family-focused therapy , interpersonal and social rhythm therapy , and cognitive behavior therapy . Collaborative care consisted of 3 sessions in 6 weeks . MAIN OUTCOME MEASURES Outcome assessment s were performed by psychiatrists at each pharmacotherapy visit . Primary outcomes included time to recovery and the proportion of patients classified as well during each of 12 study months . RESULTS All analyses were by intention to treat . Rates of attrition did not differ across the intensive psychotherapy ( 35.6 % ) and collaborative care ( 30.8 % ) conditions . Patients receiving intensive psychotherapy had significantly higher year-end recovery rates ( 64.4 % vs 51.5 % ) and shorter times to recovery than patients in collaborative care ( hazard ratio , 1.47 ; 95 % confidence interval , 1.08 - 2.00 ; P = .01 ) . Patients in intensive psychotherapy were 1.58 times ( 95 % confidence interval , 1.17 - 2.13 ) more likely to be clinical ly well during any study month than those in collaborative care ( P = .003 ) . No statistically significant differences were observed in the outcomes of the 3 intensive psychotherapies . CONCLUSIONS Intensive psychosocial treatment as an adjunct to pharmacotherapy was more beneficial than brief treatment in enhancing stabilization from bipolar depression . Future studies should compare the cost-effectiveness of models of psychotherapy for bipolar disorder . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00012558 OBJECTIVE In a previous r and omized controlled study , the authors reported significant beneficial effects of cognitive therapy for relapse prevention in bipolar disorder patients up to 1 year . This study reports additional 18-month follow-up data and presents an overview of the effect of therapy over 30 months . METHOD Patients with DSM-IV bipolar I disorder ( N=103 ) suffering from frequent relapses were r and omly assigned into a cognitive therapy plus medication group or a control condition of medication only . Independent raters , who were blind to patient group status , assessed patients at 6-month intervals . RESULTS Over 30 months , the cognitive therapy group had significantly better outcome in terms of time to relapse . However , the effect of relapse prevention was mainly in the first year . The cognitive therapy group also spent 110 fewer days ( 95 % CI=32 to 189 ) in bipolar episodes out of a total of 900 for the whole 30 months and 54 fewer days ( 95 % CI=3 to 105 ) in bipolar episodes out of a total of 450 for the last 18 months . Multivariate analyses of variance showed that over the last 18 months , the cognitive therapy group exhibited significantly better mood ratings , social functioning , coping with bipolar prodromes , and dysfunctional goal attainment cognition . CONCLUSIONS Patients in the cognitive therapy group had significantly fewer days in bipolar episodes after the effect of medication compliance was controlled . However , the results showed that cognitive therapy had no significant effect in relapse reduction over the last 18 months of the study period . Further studies should explore the effect of booster sessions or maintenance therapy BACKGROUND Several previous studies have established that low treatment adherence is common among bipolar patients and may explain high rates of recurrence . On the other h and , some patients keep relapsing even when they strictly follow their prescribed somatic treatments . Psychological interventions such as psychoeducation may foster early recognition of prodromal symptoms and minimize the risk of relapse . To date , studies assessing the usefulness of psychoeducation in fully compliant patients are lacking . METHOD This was a single-blind , r and omized , prospect i ve clinical trial on the efficacy of group psychoeducation in remitted fully compliant DSM-IV bipolar I patients ( N = 25 ) who were compared with a group with similar characteristics ( N = 25 ) who did not receive psychoeducation . All patients received naturalistic pharmacologic treatment . Recruitment began in 1997 and follow-up was completed in January 2002 . The follow-up phase comprised 2 years during which all patients continued receiving naturalistic treatment without psychological intervention and were assessed monthly on several outcome measures . RESULTS At the end of the 2-year follow-up , 23 subjects ( 92 % ) in the control group fulfilled criteria for recurrence versus 15 patients ( 60 % ) in the psychoeducation group ( p < .01 ) . The number of total recurrences and the number of depressive episodes were significantly lower in psychoeducated patients . CONCLUSION Although the present study has the limitation of small sample size , psychoeducation showed its efficacy in preventing Output:	RESULTS Cognitive-behavioural therapy or group psychoeducation may be effective for relapse prevention in stable individuals . Family therapy was no more or less effective than individual psychosocial therapy or crisis management . There is no evidence that care management or integrated group therapy is effective in the prevention of relapse . CONCLUSIONS Cognitive-behavioural therapy , group psychoeducation and possibly family therapy may be beneficial as adjuncts to pharmacological maintenance treatments
MS2962	*TASK* the task is to summarize an input biomedical literature in six sentences *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 OBJECTIVES To study the adaptation and readaptation processes to 1 week of night work ( 6:30 PM to 6:30 AM ) followed by 1 week of day work ( 6:30 AM to 6:30 PM ) . DESIGN Part of a r and omized , placebo-controlled , crossover field study . Here , data from the placebo arm are presented . SETTING Oil rig in the North Sea . Work schedule : 2 weeks on a 12-hour shift , with the first week on the night shift and the second week on the day shift . PARTICIPANTS Subjects complaining about problems with adjusting to shift work . Seventeen workers completed the study . INTERVENTIONS N/A. MEASUREMENTS Subjective and objective measures of sleepiness ( Karolinska Sleepiness Scale and simple serial reaction time test ) and sleep ( diary and actigraphy ) . RESULTS Both subjective and objective measures improved gradually during night work . The return to day work after 1 week on the night shift led to a clear increase in subjective sleepiness and worsening of sleep parameters . During the week on the day shift , sleepiness and sleep gradually improved , similar to the improvement seen during night work . The workers indicated that the day shift was worse than the night shift on some of the measures , e.g. , sleep length was significantly longer during the night-shift period . CONCLUSIONS This is one of few studies showing how shift workers in a real-life setting adjust to night work . Both subjective and objective sleepiness and subjective sleep improved across days . The effects were especially pronounced for the subjective data Previously we have shown that the 6-sulphatoxymelatonin rhythm of oil rig workers on a 2-week night shift ( 1800 - 0600 h ) adapts to the shift via a phase delay . We now report the findings of a study on two offshore drill crews working a 1 week day ( 1200 - 0000 h ) , 1 week night ( 0000 - 1200 h ) swing shift . Urine sample s were collected every 2 - 3 h throughout the subjective days , with over-sleep collection s , for the measurement of 6-sulphatoxymelatonin by radioimmunoassay . One crew ( n = 11 ) , studied in November , showed no change in their 6-sulphatoxymelatonin rhythm during night shift . The other crew ( n = 7 ) , studied in March , showed a significant phase advance of the rhythm during night shift . The data indicate that both the type of shift and the season influence the direction and degree of adaptation Background : Melatonin shows potential oncostatic activity and is acutely suppressed by light exposure . Some evidence suggests an association between night work and breast cancer risk , possibly through the melatonin pathway . Methods : In a cohort of premenopausal nurses , we prospect ively studied the relation between rotating night shift work and breast cancer risk . Total number of months during which the nurses worked rotating night shifts was first assessed at baseline in 1989 and periodically up date d thereafter . We used Cox proportional hazards models to calculate relative risks ( RRs ) and 95 % confidence intervals ( CIs ) . Results : Among 115,022 women without cancer at baseline , 1,352 developed invasive breast cancer during 12 years of follow up . Women who reported more than 20 years of rotating night shift work experienced an elevated relative risk of breast cancer compared with women who did not report any rotating night shift work ( multivariate RR = 1.79 ; 95 % CI = 1.06–3.01 ) . There was no increase in risk associated with fewer years of rotating night work . Conclusion : Our results suggest a modestly elevated risk of breast cancer after longer periods of rotating night work . Additional studies are warranted to rule out small sample size or uncontrolled sources for confounding as alternative explanations Previous research indicates that night workers ' circadian rhythms do not adapt to night work and that disturbed sleep and wakefulness persist , even after weeks of working on night shift . We studied adjustment to 14 days of consecutive night work at an oil platform and the readjustment to day life at home , using the Karolinska sleep/wake diary . The platform workers adapted to night work within a few days , as indicated by the rapid reduction of night-work sleepiness , and by the gradual delay of bedtime to an hour commensurate with the behavior of day workers . Readaptation to day life was slower and more difficult , adding evidence of a complete adaptation to night work . We conclude that the lack of conflicting exposure to daylight in the morning may have facilitated the rapid adjustment to night work STUDY OBJECTIVES Although there are considerable data demonstrating the impact of shift work on sleep and alertness , little research has examined the prevalence and consequences of shift work sleep disorder in comparison to the difficulties with insomnia and excessive sleepiness experienced by day workers . The present study was design ed to determine the relative prevalence and negative consequences associated with shift work sleep disorder in a representative sample drawn from the working population of metropolitan Detroit . DESIGN R and om-digit dialing techniques were used to assess individuals regarding their current work schedules and a variety of sleep- and non-sleep-related outcomes . SETTING Detroit tricounty population . PARTICIPANTS A total of 2,570 individuals aged 18 to 65 years from a representative community-based sample including 360 people working rotating shifts , 174 people working nights , and 2036 working days . MEASUREMENTS AND RESULTS Using st and ardized techniques , individuals were assessed for the presence of insomnia and excessive sleepiness , based on DSM-IV and ICSD criteria . Those individuals with either insomnia or excessive sleepiness and who were currently working rotating or night schedules were classified as having shift work sleep disorder . Occupational , behavioral , and health-related outcomes were also measured . Individuals who met criteria for shift work sleep disorder had significantly higher rates of ulcers ( odds ratio = 4.18 , 95 % confidence interval = 2.00 - 8.72 ) , sleepiness-related accidents , absenteeism , depression , and missed family and social activities more frequently compared to those shift workers who did not meet criteria ( P < .05 ) . Importantly , in most cases , the morbidity associated with shift work sleep disorder was significantly greater than that experienced by day workers with identical symptoms . CONCLUSION These findings suggest that individuals with shift work sleep disorder are at risk for significant behavioral and health-related morbidity associated with their sleep-wake symptomatology . Further , it suggests that the prevalence of shift work sleep disorder is approximately 10 % of the night and rotating shift work population OBJECTIVES This study evaluated the effects of bright light and melatonin on adaptation to night work on an oil rig in the North Sea . METHODS Seventeen persons working a schedule of 2 weeks on a 12-hour shift , with the first week on night shift and the second week on day shift ( ie , the swing shift schedule ) participated . In a r and omized controlled crossover design , the shift workers received a placebo , melatonin ( 3 mg , 1 hour before bedtime ) , or bright light ( 30-minute exposure , individually scheduled ) during the first 4 days on the night shift and during the first 4 days on the day shift . Subjective and objective measures of sleepiness ( Karolinska Sleepiness Scale and a simple serial reaction-time test ) and sleep ( diary and actigraphy ) were recorded . RESULTS Subjective measures indicated that melatonin modestly reduced sleepiness at work during the day shift and increased sleep by 15 - 20 minutes per day . Bright light gave values in between those of melatonin and the placebo , but with few significant results . According to the objective measures , bright light improved sleep to a minor degree during the night shift . Hardly any side-effects were reported . CONCLUSIONS Melatonin and bright light modestly improved sleep and sleepiness in this field study . In well-controlled simulated nightwork studies , both melatonin and bright light are more effective in alleviating sleepiness and sleep problems . The less effect in this field study may be due to competing or conflicting factors present in real life or to an inoptimal timing and duration of the treatments Output:	In conclusion , the longitudinal studies were generally consistent in showing that adaptation to night work was complete within one to two weeks of work , while re-adaptation to a daytime schedule was slower . Shift workers reported more sleep problems than day workers .
MS2963	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Clinical investigators are increasingly testing treatments that have the primary benefit of decreased burden or harms relative to an existing st and ard . The goal of the result ing r and omized trials -- called noninferiority trials -- is to establish that the novel treatment 's effectiveness is not substantially less than the existing st and ard . Conclusions from these trials are , however , based on noninferiority thresholds specified by authors whose judgments may not coincide with those of patients and clinicians . This article highlights issues related to validity , interpretation , and applicability of results specific to noninferiority trials . Suboptimal administration of st and ard treatment or exclusive reliance on the analyze-as-r and omized approach that is st and ard for conventional superiority trials may produce misleading results in noninferiority trials . Clinicians should judge whether the novel treatment 's impact on effectiveness outcomes --the prime reason for wanting to prescribe it -- is sufficiently close to that of st and ard treatment that they are comfortable substituting it for the existing st and ard . Trading off desirable and undesirable consequences is an individual decision : given the benefits of a novel treatment , some patients may perceive the uncertainty regarding a reduction in treatment effectiveness as acceptable while others may not Background : Individuals with type 2 diabetes mellitus have impairments in early insulin release , result ing in increased postpr and ial glucose excursions and suboptimal glycemic control . Studies with Technosphere ® Insulin ( TI ) indicate that it has rapid systemic absorption and a short duration of glucose-lowering activity , making it well suited for controlling postpr and ial glucose levels . Methods : The goal of this phase 2b , prospect i ve , multicenter , double-blind , placebo-controlled study was to characterize the dose response of four different doses ( equivalent to 3.6 , 7.3 , 10.9 , and 14.6 U subcutaneous regular human insulin ) of pr and ial TI or Technosphere powder alone administered before each of three meals daily , in combination with insulin glargine over an 11-week treatment period , in patients with type 2 diabetes and suboptimal glycemic control . Conclusions : This study demonstrated that , over 11 weeks , TI plus basal insulin glargine is well tolerated and results in dose-dependent reductions in postpr and ial glucose and HbA1c levels . Results : The study enrolled 227 patients . In all dose groups , TI demonstrated statistically significant dose-dependent reductions in hemoglobin A1c ( HbAlc ) versus baseline ( −0.4 , −0.5 , −0.5 , and −0.6 for 3.6 , 7.3 , 10.9 , and 14.6 U equivalents , respectively ; p < 0.05 in all groups ) , as well as versus placebo or Technosphere powder alone ( −0.40 , −0.67 , −0.70 , and −0.78 for 3.6 , 7.3 , 10.9 , and 14.6 U equivalents , respectively ; p < 0.04 in all groups ) . It reduced the postpr and ial maximum glucose concentration within each treatment group ( statistically significant in all but the TI 3.6 U-equivalent group ) and reduced the postpr and ial area under the glucose curve ( statistically significant for the TI 10.9 and 14.6 U-equivalent groups ) versus placebo . There were no cases of severe hypoglycemia , while mild/moderate hypoglycemia was observed most frequently in the highest dosage groups , as expected . Rates of cough were low and comparable among all groups . No clinical ly relevant changes in pulmonary function tests , body weight , or high-resolution computerized axial tomography and magnetic resonance imaging were observed 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 The development of pulmonary insulin formulation offers an attractive alternative to the current requirement of repeated subcutaneous ( s.c . ) injections for insulin administration . Technosphere/Insulin is a formulation of regular human insulin that was design ed to produce an efficient transport of insulin across the respiratory epithelium into the systemic circulation . Several studies using the euglycemic clamp technique were performed in healthy volunteers and patients with Type 2 diabetes to assess the pharmacokinetic and pharmacodynamic properties of Technosphere/Insulin . The investigations revealed a very rapid systemic insulin uptake ( insulin T(max ) approximately 12 - 14 min ) , a fast onset of action ( maximum activity approximately 20 - 30 min ) , and a short duration of action ( approximately 2 - 3 h ) in healthy volunteers and in patients with Type 2 diabetes . In the first study , employing a commercially available inhaler , the relative bioavailability ( compared with s.c . injections ) was initially reported to be 26 % for the first 3 h and 16 % for the entire observation period of 6 h. With the development of a specific inhaler adapted to the physical properties of Technosphere/Insulin , the MedTone Inhaler , relative bioavailability was 50 % for the first 3 h and 30 % over the entire 6-h period . A clear linearity of systemic insulin uptake was observed in a study employing 12 healthy volunteers inhaling doses of 25 , 50 , and 100 IU . Repeated inhalation of 100 IU of Technosphere/Insulin by 12 patients with Type 2 diabetes revealed a lower variability in comparison with published s.c . injection data from healthy volunteers . This new Technosphere/Insulin formulation was well tolerated , and no serious adverse events were reported in any of the investigations . Given its attractive time-action profile , Technosphere/Insulin may become a suitable alternative to s.c . injection for pr and ial insulin delivery , especially in patients with Type 2 diabetes , if the long-term safety , tolerability , and efficacy of this pulmonary insulin are established and confirmed in future studies AIMS This study assessed patient-reported outcomes in a multicenter study of adults with type 2 diabetes taking mealtime Technosphere ( ® ) inhaled insulin ( MannKind Corp. , Valencia , CA ) and basal insulin ( insulin glargine ) or premixed aspart insulin 70/30 . METHODS Subjects were 618 non-smoking adults with starting hemoglobin A1c > 7.0 % : 302 in the Technosphere+glargine ( TI+G ) arm and 316 in the biphasic rapid-acting insulin arm ( premixed aspart insulin 70/30 ) . Subjects ( 47 % male ; mean age , 56 years ; mean duration of diagnosed diabetes , 13.4 years ) completed a measure of health-related quality of life ( the SF-36 ) and a measure of treatment satisfaction ( the Inhaled Insulin Treatment Question naire [ IITQ ] ) before starting insulin treatment and approximately 45 weeks later . RESULTS There were no significant changes in either treatment arm for SF-36 Physical or Mental Component Summary measures . IITQ Diabetes Worries declined significantly in the TI+G arm ( P=0.008 ) , and Perceptions of Insulin Therapy , Treatment Satisfaction , and Treatment Preference improved in both arms ( all P<0.001 ) ; there were no significant between-arm differences in change on any of these measures . CONCLUSIONS Treatment with inhaled Technosphere insulin was implemented without a negative impact on health-related quality of life and with a reduction in diabetes worries . Improvements in perceptions of insulin therapy , treatment satisfaction , and treatment preference did not differ from treatment with premixed aspart insulin AIMS Development of inhaled insulin has increased the need to underst and its pulmonary safety . This study evaluated pulmonary function changes in diabetes patients receiving inhaled Technosphere Insulin ( TI ) or usual antidiabetes treatment ( usual care ) . METHODS This r and omized , open-label study was conducted at 220 sites ( 25 July 2005 to 29 August 2008 ) . Pulmonary function tests [ forced expiratory volume in 1 s ( FEV(1 ) ) , forced vital capacity ( FVC ) , total lung capacity ( TLC ) and lung diffusion capacity for carbon monoxide ( DL(CO ) ) ] were prospect ively followed over 2 years in patients with type 1 or type 2 diabetes receiving TI ( n = 730 ) or usual care ( n = 824 ) , along with a cohort without diabetes not receiving any specific therapy ( n = 145 ) . RESULTS Baseline demographics and pulmonary function were similar between diabetes treatment groups . Lung function declined from baseline in all groups . TI was non-inferior to usual care for mean change in FEV(1 ) from baseline to month 24 [ mean ( s.e.m . ) 0.037 ( 0.0119 ) l ; 95 % CI 0.014 to 0.060 ] using mixed-model repeated-measure with a pre-specified non-inferiority margin of 50 ml/year . After a greater initial decline at month 3 with TI , rate of change ( slope ) in FEV(1 ) , FVC and DL(CO ) ( months 3 - 24 ) was not statistically different between treatment groups . TI was well tolerated ; no serious safety concerns emerged . The most common respiratory event associated with TI was mild , transient cough , occurring within minutes of inhalation . CONCLUSIONS Observed changes in lung function with TI were small , occurred early after therapy initiation , remained non-progressive over 2 years and were unlikely to be clinical ly meaningful Background : Technosphere ® [ Bis-3 , 6(4-fumarylaminobutyl)-2 , 5-diketopiperazine ( FDKP ) ] microparticles , the integral component of the Technosphere inhalation system , deliver drugs to the deep lung and have been used to administer insulin and glucagon-like peptide-1 via inhalation in clinical studies . Three studies were conducted to characterize FDKP pharmacokinetics , including assessment s in subjects with diabetic nephropathy ( DNP ) , in subjects with chronic liver disease ( CLD ) , and in healthy subjects . Methods : An open-label , nonr and omized , two-period , fixed-sequence crossover absorption , distribution , metabolism , and excretion ( ADME ) study was conducted in six healthy nonsmoking men who received single intravenous and oral doses of [14C]FDKP solution , with serial sampling of blood , urine , feces , and expired air . Additionally , two single-dose , open-label , parallel- design studies with 20 mg of inhaled FDKP were conducted in ( 1 ) 12 diabetic subjects with normal renal function and 24 DNP subjects and ( 2 ) 12 healthy subjects and 21 CLD subjects . Results : In the ADME study , > 95 % of the intravenous dose and <3 % of the oral dose were recovered in urine , with no evidence of metabolism . No significant pharmacokinetic differences were observed between healthy subjects and CLD subjects [ geometric mean ( % coefficient of variation ) area under the curve from time 0 to 480 minutes ( AUC0 - 480 ) : 26,710 ( 34.8 ) and 31,477 ( 28.8 ) ng/ml·min , respectively ] . Maximum observed drug concentration ( C max ) and AUC0 - 480 were higher in DNP subjects than in subjects with normal renal function [ C max : 159.9 ( 59.4 ) ng/ml versus 147.0 ( 44.3 ) ng/ml ; AUC0 - 480 : 36,869 ( 47.2 ) ng/ml·min versus 30,474 ( 31.8 ) ng/ml·min ] . None of the differences observed were considered clinical ly significant . Conclusions : Fumaryl diketopiperazine is predominantly cleared unchanged by the kidney with essentially no oral bioavailability . Technosphere is a safe delivery vehicle for medications administered via inhalation AIM AFRESA [ Technosphere Insulin ( TI ) ; MannKind Corporation , Valencia , CA ] , a dry powder preparation of regular human insulin ( RHI ) , utilizes a novel and versatile drug carrier platform that enables pulmonary administration of medications typically administered by injection . The aim of this study was to compare the pharmacokinetic ( PK ) and pharmacodynamic ( PD ) parameters of three different inhaled doses of TI with those of subcutaneous ( s.c . ) RHI . METHODS This r and omized , open-label , four-way crossover study of 11 healthy , non-smoking volunteers evaluated PK and PD profiles following single inhalations of 25 , 50 or 100 U TI and 10 IU RHI administered subcutaneously using a euglycaemic clamp technique . RESULTS Following inhalation of TI , peak insulin concentrations ( C(max ) ) were achieved approximately 2 h earlier than with RHI ( 12 - 17 min for TI vs. 134 min for RHI ) . Area under the insulin concentration-time curve ( AUC ) and insulin C(max ) values increased with increasing TI dose . Insulin Output:	INTERPRETATION Glycaemic efficacy of Technosphere inhaled insulin is lower than that of subcutaneous insulin , but inhaled insulin has a lower risk of severe hypoglycaemia and weight gain .
MS2964	*TASK* the task is to summarize an input biomedical literature in six sentences *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 double-blind controlled therapeutic trial of factorial design was used to study the therapeutic effects of lorazepam , hyoscine butylbromide , and ispaghula husk in 12 r and omised blocks of eight patients with the irritable bowel syndrome ( IBS ) . Each of the three agents caused a sustained symptomatic improvement in some of the patients , although only with ispaghula was the difference between the real and dummy preparation statistically significant . When the eight possible combinations of treatment were analysed none of the 12 patients who received only dummy preparations of the three agents had maintained any improvement over the three months of the trial . Seven patients improved among the 12 who received potent preparations of all three agents , and between four and six patients improved in the groups receiving one or two of the potent preparations . These therapeutic results , though far from perfect , show that the types of drug commonly used to treat IBS are of some value and may be additive in their effects . Similar combinations of other therapeutic agents may be more effective , but it will be possible to determine this only by carrying out factorial therapeutic trials This placebo controlled , double-blind , cross-over trial involving 20 patients was conducted to assess the effect of ispaghula husk on the major bowel symptoms and the whole gut transit time in irritable bowel syndrome ( IBS ) and to determine if changes in these parameters were related to global improvement . All 20 patients were interviewed at the end of the treatment periods and 14 patients kept concurrent daily records . Ispaghula therapy result ed in improvement in global symptoms and satisfying bowel movements ( P less than 0.001 ) but produced no change in abdominal pain or flatulence . There was a correlation between the improvement of well-being and the number of days of satisfying bowel movements ( P less than 0.001 ) but not with the indexes of pain , stool frequency or changes in the transit time . The easing of bowel dissatisfaction appears to be a major reason for the therapeutic success of ispaghula in IBS A double blind placebo controlled trial of ispaghula husk in 80 patients with irritable bowel syndrome is reported . Global assessment judged treatment to be satisfactory in 82 % of patients receiving ispaghula and 53 % of the placebo group ( p less than 0.02 ) . Bowel habit was unchanged in the placebo group , while constipation significantly improved in patients taking ispaghula ( p = 0.026 ) . Transit time decreased significantly in those taking ispaghula compared with placebo ( p = 0.001 ) , especially in patients with initially high transit times . Abdominal pain and bloating improved in both groups , with no significant differences between ispaghula and placebo . Four of the eight withdrawals on ispaghula and 10 of the 15 withdrawals on placebo were because of treatment failure . Ispaghula significantly improves overall well being in patients with irritable bowel syndrome , and in those with constipation favourably affects bowel habit and transit time Comment Our results confirm that the natural defences of the peritoneum can deal successfully with infection if unhampered by the dialysis fluid . ' Temporary interruption of dialysis avoids protein loss and fluid retention due to peritoneal inflammation , limits the use of costly or toxic antibiotics , and preserves remaining renal function . We found that our patients , having been treated by interruption of dialysis once , subsequently tended to refer themselves early in the hope of being able to receive this short treatment again . The treatment avoids the loss of phagocytic cells and opsonins that occurs during dialysis and allows these cells to be concentrated into a small volume of peritoneal fluid , thus increasing the chance of phagocytosis . It also avoids the detrimental effect of dialysis fluid on phagocytic cells,2 which may enhance survival of bacteria within leucocytes,3 and on the mesothelial cells.4 Interruption of dialysis was regularly effective and was not detrimental to peritoneal function . We believe that this was because of our careful selection of cases and recommend that the treatment is used only in the absence of contraindications . Immediate failure of this treatment was unusual . If not due to the presence of unusual pathogens it would suggest persisting infection from colonisation of the catheter or , if infection were present at the exit site , covert infection around the catheter . In either case the catheter should be removed , as in relapse of peritonitis after conventional A r and omized , double-blind trial of a psyllium preparation was initiated in 77 patients with painful irritable bowel syndrome . Sixty- patients finished and su bmi tted symptom data for 8 weeks while taking placebo ( n = 34 ) or psyllium ( n = 26 ) . Increase in normal stools and decrease in pain severity ( p less than 0.05 ) occurred equally in both groups . Subjective improvement was reported by 24 of 34 patients on placebo and 20 or 26 on psyllium ( p greater than 0.05 ) . Five symptom variables were significantly correlated ( p less than 0.05 ) with patient 's subjective global assessment ( R = 0.64 ) . Discriminant analysis of Minnesota Multiphasic Personality Inventory variables yielded overall rates of correct prediction of 66.1 % for whether patients got " much better " and 77.9 % for whether they voluntarily dropped from the study . A major placebo effect occurs in patients with painful irritable bowel syndrome and is probably responsible for the efficacy of psyllium . Personality factors influence the magnitude of therapeutic response and whether patients discontinue treatment within 8 weeks Output:	: Soluble fiber is effective in treating IBS . Bran did not appear to be of benefit , although we did not uncover any evidence of harm from this intervention , as others have speculated from uncontrolled data
MS2965	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: To evaluate the clinical effectiveness of chlorpromazine in comparison with placebo over a brief period of hospitalization , the authors conducted a double-blind study of the drug in 44 acutely ill schizophrenic patients . These patients had been newly admitted to a brief treatment unit where the average length of stay was 7 to 10 days . The results of this study indicate that chlorpromazine had no more calming or antipsychotic effect than placebo during the first 5 days of treatment . The authors suggest that 5 days is too short a time for a clinical trial to gauge patient response to chlorpromazine Summary Trifluperidol , a new butyrophenone compound , was evaluated in chronic schizophrenic women under conditions of a controlled clinical trial . Within this framework significant drug effects associated with the st and ard drug , chlorpromazine , attested to the sensitivity of the experiment , while trifluperidol , the experimental drug , was shown to be an antipsychotic agent at least equally as effective as the st and ard . The placebo group tended to deteriorate on all measures . This trend did not differ significantly from a similar trend in a group of subjects receiving neither placebo nor active treatment . The most likely explanation for this deterioration is thought to be an inadequate preliminary dry-out period , although other influences affecting all subjects adversely can not be ruled out . The demonstration of significant drug : placebo differences was dependent in part upon the presence of the negative change in the placebo group . Failure to include a control group in the present study would have precluded the demonstration of statistically significant drug effects In a series of 6 separate controlled clinical trials of antipsychotic agents in chronic schizophrenic patients , it was shown repeatedly that chlorpromazine ( CPZ ) exhibited hypercholesterolemic activity . In the analysis of covariance , the adjusted final mean difference in serum cholesterol concentrations between the placebo and CPZ groups ranged from 14 to 28 mg . per 100 ml . This activity was dose related in that it occurred with a fixed daily dose of 600 mg . administered for 24 weeks , but not with a fixed daily dose of 150 mg . or 300 mg . over the same period of time . The serum concentration of triglycerides remained unaffected under similar experimental conditions . This action of CPZ appeared unrelated to thyroid function and liver function as presently measured in the clinical laboratory . A consistent relationship to body weight changes could not be demonstrated even though increased body weight was noted to be a consistent result of CPZ therapy . In view of its extensive use as long‐term therapy , the possible role of CPZ as an atherogenic agent deserves consideration A double-blind placebo-controlled trial of chlorpromazine , using a cross-over design , is reported . There were 28 patients , showing chronic defect states , mostly schizophrenic . They lived in an isolated community , and were selected because they had had no specific therapy for at least five years , and had had no previous treatment with psychotropic drugs of any kind . Pre caution s were taken to keep their environment constant , and medication was not started until the end of a six-month observation period , in which all the procedures of a therapeutic trial , including administration of placebo , were carried out . Only one patient out of 28 showed a definite therapeutic response . Analysis of ratings for the main psychopathological symptoms did not disclose any significant changes in the group as a whole . It is argued that the value of chlorpromazine in chronic schizophrenia has been accepted without sufficient evidence of the effect of the drug in different clinical states and the specific indications for its use . Further study of the clinical features of cases which do or do not respond to phenothiazines is required Output:	There were , however , many adverse effects . Chlorpromazine is sedating ( n = 1242 , 18 RCTs , RR 2.3 CI 1.7 to 3.1 , NNH 6 CI 5 to 8) , increases a person 's chances of experiencing acute movement disorders , Parkinsonism and causes low blood pressure with dizziness and dry mouth . Conclusion It is underst and able why the World Health Organization ( WHO ) have endorsed and included chlorpromazine in their list of essential drugs for use in schizophrenia .
MS2966	*TASK* the task is to summarize an input biomedical literature in six sentences *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 impact of clinical ly diagnosed depression on recovery in activities of daily living over a 2-year follow-up was examined in a prospect i ve study of 63 stroke patients . Although impairment in activities of daily living , neurologic diagnoses and findings , lesion location and volume as measured on computed tomographic scan , demographic variables , cognitive impairment , and social functioning were comparable between depressed ( n = 25 ) and nondepressed ( n = 38 ) patients during their acute hospitalization , the two groups had different patterns of recovery in activities of daily living . At 2 years after suffering a stroke , patients with an in-hospital diagnosis of depression ( either major or minor depression ) were significantly more impaired in both physical activities and language functioning than were non-depressed patients . Among patients with major depression , this disparity in the recovery profile was present even after the depression had remitted . This study emphasizes the need for early recognition and treatment of poststroke depression The efficacy of nortriptyline in the treatment of post-stroke depression was assessed by a double-blind study in thirty-four patients . Half of the patients had major depression . There was a significantly greater improvement in depression in patients treated with nortriptyline than in a similar group of placebo-treated patients . Depression was measured by the Hamilton depression scale , Zung depression scale , present state examination , and an overall depression scale . Successfully treated patients had serum nortriptyline levels in the therapeutic range . Post-stroke depressions are common , severe , and longst and ing , and the demonstrated efficacy of nortriptyline provides an important addition to the treatments available for stroke patients The authors sought to determine the relative efficacy and tolerability of duloxetine versus citalopram and sertraline in the treatment of poststroke depression ( PSD ) , anxiety , and fatigue . A group of 60 patients with PSD were assigned to receive duloxetine , citalopram , or sertraline and were assessed over a 3-month period for depression , anxiety , and fatigue . Improvement of depression and anxiety , but not fatigue , was observed in all study groups . Duloxetine was well tolerated and significantly more effective than citalopram and sertraline for the treatment of anxiety symptoms in PSD patients . None of the antidepressants used was effective for reducing symptoms of fatigue BACKGROUND AND PURPOSE Patients with poststroke major depression have a greater severity of cognitive impairment than nondepressed patients even when matched for size and location of stroke lesion . Prior treatment studies have consistently failed to show an improvement in cognitive function even when poststroke mood disorders responded to antidepressant therapy . We examined the response of cognitive function to treatment with nortriptyline or placebo in a double-blind trial . METHODS Patients with major ( n=33 ) or minor ( n=14 ) depression participated in a double-blind treatment study with nortriptyline or placebo . They were examined for change in depressive mood , measured by the Hamilton Rating Scale for Depression ( HAM-D ) , and change in cognitive impairment , assessed by the Mini-Mental State Examination ( MMSE ) , after treatment with nortriptyline or placebo . Cognitive treatment response , as measured by the MMSE , was compared between patients whose depression did and did not respond to treatment . RESULTS Patients whose poststroke depression remitted ( predominantly associated with nortriptyline treatment ) had significantly greater recovery in cognitive function over the course of the treatment study than patients whose mood disorder did not remit ( predominantly associated with placebo treatment ) . CONCLUSIONS Our findings support the contention that poststroke major depression leads to a " dementia of depression . " Prior studies failed to show an effect of treatment because the effect size was too small . Successful treatment of depression may constitute one of the major methods of promoting cognitive recovery in victims of stroke BACKGROUND AND PURPOSE Early poststroke depression ( PSD ) is a frequent and specific entity that impairs the rehabilitation and functional recovery of hemiplegic patients . This trial was design ed to study the efficacy and tolerance of fluoxetine ( FLX ) in the treatment of early PSD . METHODS This was a multicenter , double-blind , placebo-controlled study . Recent hemiplegic patients ( <3 months ) suffering from major depressive disorder ( determined by International Classification of Diseases , 10th Revision , and Montgomery-Asberg Depression Rating Scale [ MADRS ] > 19 ) were r and omized to receive either 20 mg/d fluoxetine ( FLX ) or placebo for 6 weeks . Patients were evaluated by use of the Motricity Index , Mini-Mental State Examination , Functional Independence Measure , and MADRS . Statistical analysis was performed by using an intent-to-treat approach comparing the 2 groups at day 0 ( baseline ) and days 15 , 30 , and 45 ( end point ) . RESULTS Of 121 patients screened , 31 were included in the study , 16 in the FLX group and 15 in the placebo group . There were no significant differences in baseline characteristics among the 2 groups . The FLX-treated patients compared with placebo-treated patients demonstrated significant improvement in mean MADRS scores at end point ( 11.8+/-6 . 7 [ mean+/-SD ] versus 18.7+/-10.0 , respectively ; P=0.05 ) . FLX-treated patients compared with placebo-treated patients also demonstrated greater response rate ( 62.5 % versus 33.3 % , respectively ) and greater mean decrease of MADRS ( 16.6 versus 8.4 , respectively ; P=0.02 ) . There were no differences in motor , cognitive , or functional improvement and no significant side effects after FLX treatment , except for a patient with a moderate and transient increase of transaminases . CONCLUSIONS FLX is an efficacious and well-tolerated treatment for early PSD . Further research is needed to evaluate the efficacy and safety of long-term treatment in this population OBJECTIVE This study compared nortriptyline and fluoxetine with placebo in the treatment of depression and in recovery from physical and cognitive impairments after stroke . METHOD A total of 104 patients with acute stroke enrolled between 1991 and 1997 entered a double-blind r and omized study comparing nortriptyline , fluoxetine , and placebo over 12 weeks of treatment . The majority of patients were recruited from a rehabilitation hospital in Des Moines , Iowa , but other enrollment sites were also used . Both depressed and nondepressed patients were enrolled to determine whether improved recovery could be mediated by mechanisms unrelated to depression . Nortriptyline in doses of 25 mg/day gradually increased to 100 mg/day or fluoxetine in doses of 10 mg/day gradually increased to 40 mg/day or identical placebo were given over 12 weeks . Response to treatment of depression for individual patients was defined as a greater-than-50 % reduction in scores on the Hamilton Rating Scale for Depression and no longer fulfilling diagnostic criteria for major or minor depression . Improved recovery for a treatment group was defined as a significantly higher mean score from baseline to end of the treatment trial , compared with patients treated with placebo , on measures of impairment in activities of daily living and levels of cognitive and social functioning . RESULTS Nortriptyline produced a significantly higher response rate than fluoxetine or placebo in treating poststroke depression , in improving anxiety symptoms , and in improving recovery of activities of daily living as measured by the Functional Independence Measure . There was no effect of nortriptyline or fluoxetine on recovery of cognitive or social functioning among depressed or nondepressed patients . Fluoxetine in increasing doses of 10 - 40 mg/day led to an average weight loss of 15 . 1 pounds ( 8 % of initial body weight ) over 12 weeks of treatment that was not seen with nortriptyline or placebo . CONCLUSIONS Given the doses of medication used in this study , nortriptyline was superior to fluoxetine in the treatment of poststroke depression . Demonstrating a benefit of antidepressant treatment in recovery from stroke may require the identification of specific subgroups of patients , alternative measurement scales , or the optimal time of treatment OBJECTIVE Poststroke depression is a frequent psychiatric complication after stroke that may have strong negative impact on rehabilitation therapy and functional recovery . This study was conducted to show the efficacy and safety of early treatment with the selective serotonin reuptake inhibitor fluoxetine in post-stroke depressed patients . METHODS This double-blind , r and omized placebo-controlled study was of patients within two weeks after stroke . Moderate to severe depressed patients ( determined by Hamilton Depression Scale ( HDS ) > 15 , the Beck Depression Inventory ( BDI ) and the Clinical Global Impression ( CGI ) Scale ) were r and omized to receive either 20 mg/d fluoxetine or placebo for 3 months . Beside the psychiatric assessment , patients were evaluated by use of the Sc and inavian Stroke Scale ( SSS ) , the Mini-Mental-State-Examination ( MMSE ) and the Barthel-Index ( BI ) . An open-label long-term follow up was done 18 months after the initial assessment . RESULTS 54 depressed patients of an inpatient population of 242 consecutive stroke patients aged 25 to 85 years entered the trial within the first two weeks post-stroke . 50 patients completed the trial per- protocol . The initial severity of depression was comparable in the two groups ( mean baseline HDS score 32.8 in the fluoxetine vs. 30.3 in the placebo group ) , as were neurological symptom severity and demographic parameters . Significant improvement was seen in both groups within 4 weeks of treatment , whereas no advantages of fluoxetine could be observed at this time . This indicates a high degree of spontaneous recovery during early rehabilitation therapy . BDI scores of patients treated with fluoxetine further decreased until the follow-up at 12 weeks , whereas the scores increased again in the placebo group . This depressive relapse of the placebo patients after the end of most rehabilitation efforts was evident at a long-term follow-up 18 months after inclusion , when patients who had been treated with fluoxetine were significantly less depressed . No side effects of fluoxetine treatment were detected . CONCLUSIONS The advantages of fluoxetine were obvious at the follow-up 18 months after inclusion , but could not be demonstrated within the first three months of controlled treatment . The multitude of therapeutic efforts that take place in the early phase of rehabilitation might have facilitated spontaneous recovery from depression and might have hindered benefits of antidepressant treatment to become obvious . Fluoxetine treatment was well tolerated and safe Background and Purpose The aim of the study was to investigate the efficacy and safety of the selective serotonin reuptake inhibitor citalopram in treating poststroke depression , since available treatments are usually poorly tolerated . Methods A 6-week double-blind , placebo-controlled trial was undertaken . Diagnosis and outcome were determined using the Hamilton Depression Scale , and unwanted effects were measured using the UKU side effect rating scale . Sixtysix consecutive depressed patients from an unselected population of 285 stroke patients aged 25 to 80 years entered the trial 2 to 52 weeks after stroke . They were assigned to equally sized treatment and placebo groups . The initial level of depression was comparable in the two groups ( mean baseline Hamilton Depression scores , 19.4 and 18.9 , respectively ) . Demographic parameters were also comparable in the two groups . Results Significantly greater improvement was seen in patients treated with citalopram ( 10 to 40 mg/d ) for 3 and 6 weeks , both when including all patients ( intention-to-treat analysis , p<.05 ) and excluding patients who dropped out during the first 3 weeks ( efficacy analysis , P<.005 ) . Half of the 28 patients who entered the trial 2 to 6 weeks after stroke recovered within 1 month , independent of the treatment given . This indicates a high degree of spontaneous recovery in the early phase after stroke . In contrast , recovery was infrequent in placebo group patients who became depressed 7 weeks or more after stroke . No serious side effects related to the treatment were detected ; those present were mild and usually transient . Conclusions This trial demonstrates that the selective serotonin reuptake inhibitor citalopram offers an advantageous new treatment of poststroke depression that is both safe and effective The incidence of depression following a hemispheric stroke ranges from 25 to 60 % . The benefit of antidepressant therapy on the outcome of rehabilitation in the subacute post-stroke phase is well known . We studied subjects both with and without evidence of depression , as indicated by any one of three criteria : ( i ) Clinical diagnosis of depression , ( ii ) Abnormal Zung-depression score . ( iii ) Abnormal dexamethasone suppression test ( DST ) . Patients in a stroke rehabilitation program ( 22 ) were r and omized to receive either placebo or 300 mg/day trazodone-HCl , beginning 30 days after the stroke . Patients with either a clinical diagnosis of depression or abnormal Zung depression scores showed a consistent trend towards greater improvement in Barthel activities of daily living ( ADL ) scores , with antidepressant therapy , as compared to patients receiving placebo . An abnormal DST was associated with significant improvement in the ADL scores in subjects receiving trazodone , i.e. , in post-stroke depression such a treatment seems to be beneficial BACKGROUND Poststroke depression is a frequent condition and important to treat . The aim of this trial was to study the efficacy and tolerability of sertraline . METHOD In 4 Swedish stroke centers , 123 patients ( aged 70.7 + /- 9.9 years ) were enrolled during the period September 1998 to January 2001 in a r and omized , double- Output:	All drugs were significantly more effective than placebo apart from sertraline , nefiracetam and fluoxetine . After weighing the efficacy and acceptability , we conclude that paroxetine might be the best choice when starting acute treatment for PSD , and fluoxetine might be the worst choice .
MS2967	*TASK* the task is to summarize an input biomedical literature in six sentences *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-six untreated patients with childhood with acute lymphoblastic leukemia ( ALL ) were r and omized to receive one of three remission induction regimens : vincristine and prednisone ( VP ) , vincristine , prednisone and daunorubicin ( VPD ) , or vincristine , prednisone and adriamycin ( VPA ) . The complete remission rate was similar for all three groups . Although the anthracycline regimens caused somewhat more rapid leukemic cell reduction than the VP only group , this difference was not significant . Labeling index reduction between study days 1 and 5 was significantly greater ( p less than 0.001 ) with an anthracycline than for the VP group , but there was no difference between the two anthracyclines . Granulocytopenia during induction was significantly increased ( p less than 0.05 ) in both the VPD and VPA groups as compared with VP alone . A significantly higher rate of infectious morbidity ( p less than 0.01 ) was associated with the addition of either anthracycline , but to date no significant differences in remission duration or survival have been observed . The addition of anthracyclines to VP for remission induction in childhood ALL has theoretical advantages , but may be undesirable because of increased morbidity Two groups of children with acute lymphoblastic leukemia or non-Hodgkin lymphoma , treated with anthracyclines ( ANT ) , were studied : group I , consisting of 10 patients , with coenzyme Q10 ( CoQ ) therapy ; group II , consisting of 10 patients without CoQ therapy . The ANT cumulative dose was 240 + /- 20.0 mg/m2 in group I and 252.0 + /- 20.1 mg/m2 in group II . Echocardiographic study was performed at the beginning , at the cumulative dose of 180 mg/m2 and at the end of therapy with ANT . Percentage left ventricular fractional shortening ( % LVFS ) decreased from baseline ( 40.36 + /- 4.6 ) to end value ( 35.82 + /- 5.02 ) ( P < 0.05 ) in group I ; % LVFS decreased from baseline ( 39.89 + /- 4.37 ) to end value ( 33.43 + /- 3.46 ) ( P < 0.002 ) in group II . Interventricular septum wall thickening decreased only in group II from baseline ( 46.10 + /- 10.1 ) to end therapy ( 27.00 + /- 18.54 ) ( P < 0.01 ) . Septum wall motion abnormalities were detected only in 2 patients of group II . These data demonstrate a protective effect of CoQ on cardiac function during therapy with ANT The Dana-Farber Cancer Institute ( DFCI ) acute lymphoblastic leukemia ( ALL ) Consortium Protocol 91 - 01 was design ed to improve the outcome of children with newly diagnosed ALL while minimizing toxicity . Compared with prior protocol s , post-remission therapy was intensified by substituting dexamethasone for prednisone and prolonging the asparaginase intensification from 20 to 30 weeks . Between 1991 and 1995 , 377 patients ( age , 0 - 18 years ) were enrolled ; 137 patients were considered st and ard risk ( SR ) , and 240 patients were high risk ( HR ) . Following a 5.0-year median follow-up , the estimated 5-year event-free survival ( EFS ) + /- SE for all patients was 83 % + /- 2 % , which is superior to prior DFCI ALL Consortium protocol s conducted between 1981 and 1991 ( P = .03 ) . There was no significant difference in 5-year EFS based upon risk group ( 87 % + /- 3 % for SR and 81 % + /- 3 % for HR , P = .24 ) . Age at diagnosis was a statistically significant prognostic factor ( P = .03 ) , with inferior outcomes observed in infants and children 9 years or older . Patients who tolerated 25 or fewer weeks of asparaginase had a significantly worse outcome than those who received at least 26 weeks of asparaginase ( P < .01 , both univariate and multivariate ) . Older children ( at least 9 years of age ) were significantly more likely to have tolerated 25 or fewer weeks of asparaginase ( P < .01 ) . Treatment on Protocol 91 - 01 significantly improved the outcome of children with ALL , perhaps due to the prolonged asparaginase intensification and /or the use of dexamethasone . The inferior outcome of older children may be due , in part , to increased intolerance of intensive therapy BACKGROUND Doxorubicin chemotherapy is very effective in children with acute lymphoblastic leukemia ( ALL ) but also injures myocardial cells . Dexrazoxane , a free-radical scavenger , may protect the heart from doxorubicin-associated damage . METHODS To determine whether dexrazoxane decreases doxorubicin-associated injury of cardiomyocytes , we r and omly assigned 101 children with ALL to receive doxorubicin alone ( 30 mg per square meter of body-surface area every three weeks for 10 doses ) and 105 to receive dexrazoxane ( 300 mg per square meter ) followed immediately by doxorubicin . Serial measurements of serum cardiac troponin T were obtained in 76 of 101 patients in the doxorubicin group and 82 of 105 patients in the group given dexrazoxane and doxorubicin . A total of 2377 serum sample s ( mean , 15.1 sample s per patient ) were obtained before , during , and after treatment with doxorubicin . Troponin T levels were evaluated in a blinded fashion to determine whether they were elevated ( > 0.01 ng per milliliter)--the primary end point -- or extremely elevated ( > 0.025 ng per milliliter ) . RESULTS Elevations of troponin T occurred in 35 percent of the patients ( 55 of 158 ) . Patients treated with doxorubicin alone were more likely than those who received dexrazoxane and doxorubicin to have elevated troponin T levels ( 50 percent vs. 21 percent , P<0.001 ) and extremely elevated troponin T levels ( 32 percent vs. 10 percent , P<0.001 ) . The median follow-up was 2.7 years . The rate of event-free survival at 2.5 years was 83 percent in both groups ( P=0.87 by the log-rank test ) . CONCLUSIONS Dexrazoxane prevents or reduces cardiac injury , as reflected by elevations in troponin T , that is associated with the use of doxorubicin for childhood ALL without compromising the antileukemic efficacy of doxorubicin . Longer follow-up will be necessary to determine the influence of dexrazoxane on echocardiographic findings at four years and on event-free survival Summary During the 1970s , despite apparently similar treatment , the prognosis for children with lymphoblastic leukaemia ( ALL ) improved more in some countries , notably the United States and West Germany , than in others . To find out why , the first phase of the United Kingdom ( UK ) Medical Research Council ( MRC ) childhood ALL trial , UKALL VIII , was design ed to see whether similar results to the United States Children 's Cancer Study Group ( CCSG ) could be obtained in the U.K. using an identical protocol ( CCG 162 ) . Protocol 162 was one of a series of regimens devised by the American Children 's Cancer Study Group in the 1970s and was used specifically for their average risk patients ( all children with ALL with an initial white cell count up to 50 × 109/l except those aged 3–6 years with white cell counts under 10 × 109/l ) . One arm ( 1A ) of their study was adopted by the MRC for all children in the U.K. aged 0–14 years with confirmed ALL PURPOSE Acute doxorubicin-induced cardiotoxicity can be prevented in adults by continuous infusion of the drug , but mechanisms of cardiotoxicity are different in children . We compared cardiac outcomes in children receiving bolus or continuous infusion of doxorubicin . PATIENTS AND METHODS In a r and omized study , children with high-risk acute lymphoblastic leukemia received doxorubicin 360 mg/m(2 ) in 30-mg/m(2 ) doses every 3 weeks either by bolus ( within 1 hour , n = 57 ) or by continuous infusion ( over 48 hours , n = 64 ) . Echocardiograms obtained before doxorubicin and at longest follow-up times were central ly remeasured , and z scores of cardiac measurements were calculated based on a healthy population . RESULTS The groups were similar in age , sex distribution , doxorubicin dose , and duration of follow-up . Before treatment , measures of left ventricular ( LV ) structure and function did not reveal dilated cardiomyopathy and were not statistically different between bolus and continuous-infusion groups . The follow-up echocardiograms demonstrated no significant difference between the two groups for any cardiac characteristic , but both groups showed significant abnormalities of LV structure and function compared with normal and with baseline . For example , the mean LV fractional shortening fell by approximately two SD in both groups between the two echocardiograms . LV contractility was depressed in both groups ( for bolus patients , median z score = -0.70 SD , P = .006 ; for continuous-infusion patients , median z score = -0.765 , P = .005 ) . Dilated cardiomyopathy and inadequate LV hypertrophy were noted in both groups . Clinical cardiac manifestations and event-free survival did not differ . CONCLUSION Continuous doxorubicin infusion over 48 hours for childhood leukemia did not offer a cardioprotective advantage over bolus infusion . Both regimens were associated with progressive sub clinical cardiotoxicity . Other cardioprotective strategies should be explored BACKGROUND Daunorubicin ( DNR ) is one of the most important drugs in treatment of acute lymphoblastic leukemia ( ALL ) . Prolonged infusions of anthracyclines are less cardiotoxic but it has not been investigated whether the in vivo leukemic cell kill is equivalent to short-term infusions . PROCEDURE In the cooperative treatment study COALL-92 for childhood ALL 178 patients were r and omized to receive in a therapeutic window a single dose of 36 mg/m ( 2 ) DNR either as a 1-h ( 85 patients ) or 24-h infusion ( 93 patients ) . Daily measurements of white blood cell count ( WBC ) and peripheral blood smears for seven days could be evaluated central ly in 101 patients ( 1-h : 43 patients , 24-h : 58 patients ) . RESULTS The proportional decline of blasts at day 7 after DNR infusion showed no statistically significant difference between the two treatment arms . At day 3 the median percentage of blasts was less than 10 % , at day 7 less than 2 % for either the 1-h or 24-h infusion . Twelve patients ( 1-h : 5 patients , 24-h : 7 patients ) had an absolute number of more than 1000 blasts per mul peripheral blood ( PB ) at day 7 after DNR infusion ( DNR poor responders ) . Kaplan-Meier analysis showed an equal probability of EFS for the short- and long-term infusion group ( 24-h : 83%+/-5 ; 1-h : 81+/-6 ) after a median observation time of 12.3 years . CONCLUSIONS We conclude that in children with ALL a 24-h infusion of DNR has the same in vivo cytotoxicity for leukemic cells as a 1-h infusion . This offers the possibility to use prolonged infusions with hopefully less cardiotoxicity without loss of efficacy Background . Improved survival of children with acute lymphoblastic leukemia ( ALL ) has made it more difficult to develop new protocol s to further improve results . The authors report the pilot experience with the Memorial Sloan‐Kettering‐New York‐II ( MSK‐NY‐II ) protocol , based on the New York regimen with changes made in an attempt to improve efficacy while reducing toxicity PURPOSE Dexrazoxane is a drug used to prevent anthracycline-induced cardiotoxicity . A recent report found an association between the use of dexrazoxane and the risk of developing secondary malignant neoplasms ( SMNs ) in children with Hodgkin 's disease . We report the absence of an association of SMNs in children with acute lymphoblastic leukemia ( ALL ) treated on Dana-Farber Cancer Institute ALL Consortium Protocol 95 - 01 . PATIENTS AND METHODS Two hundred five children with high-risk ( HR ) ALL were r and omly assigned to receive doxorubicin alone ( n = 100 ) or doxorubicin with dexrazoxane ( n = 105 ) during the induction and intensification phases of multiagent chemotherapy . We compared incidence of SMNs in these two groups . RESULTS With a median follow-up of 6.2 years , no differences in the incidence of SMNs were noted between the group that received dexrazoxane and the Output:	Data from 958 patients in 4 trials , recruiting between 1972 and 1984 , showed that addition of an anthracycline reduced bone marrow relapse and , non-significantly , non-bone marrow relapse , result ing in an increased relapse-free interval . The limited data from trials did not demonstrate differences in clinical ly evident cardiotoxicity . Anthracyclines are effective against bone marrow relapse but have not been shown to significantly increase event free survival in childhood ALL .
MS2968	*TASK* the task is to summarize an input biomedical literature in six sentences *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 recently concluded the third decade of large-scale public funding for community-based drug abuse treatment in the United States . Over these years , basic and applied research in this arena has been carried out and reported at an unprecedented rate , based in part on the requirements of federal agencies to evaluate the effectiveness of our national drug abuse treatment system . Beginning in the early 1970s with the Drug Abuse Reporting Program ( DARP ) , followed by the Treatment Outcome Prospect i ve Study ( TOPS ) a decade later , and continuing through the 1990s with the Drug Abuse Treatment Outcome Studies ( DATOS ) , national evaluations have examined over 65,000 admissions to 272 treatment programs using multimodality and multisite sampling plans that allow the study of treatment in natural setting s. These national projects comprise only part of the large body of evidence accumulated over the past 30 years that supports the general effectiveness of drug treatment.1 - Integrated mental health and substance abuse treatment within an assertive community treatment ( ACT ) approach was compared to that within a st and ard case management approach for 223 patients with dual disorders over three years . ACT patients showed greater improvements on some measures of substance abuse and quality of life , but the groups were equivalent on most measures , including stable community days , hospital days , psychiatric symptoms , and remission of substance use disorder Jail recidivists with serious mental illness and substance use disorders were treated in an in-custody setting and then r and omly assigned to either a high fidelity Integrated Dual Disorders Treatment program ( 103 participants ) or to service as usual ( 79 participants ) . Outcomes were tracked an average of 18 months from program entry at the termination of the initial incarceration . A reduction in jail days from baseline to study period was significant for both groups . The pre to post reduction for arrests and total convictions was significant in the experimental group but not the control group . However , during the study period , differences between experimental and control groups in arrests , convictions and jail days were not statistically significant . Experimental participants had lower study period psychiatric inpatient and crisis utilization and greater outpatient utilization than did control group participants . The groups did not differ with regard to total institutional days . Experimental group attrition was relatively high BACKGROUND Few r and omised controlled trials have been aim ed specifically at substance use reduction among people with psychotic disorders . AIMS To investigate whether a 10-session intervention consisting of motivational interviewing and cognitive-behavioural therapy ( CBT ) was more efficacious than routine treatment in reducing substance use and improving symptomatology and general functioning . METHOD A community sample of people with a psychotic disorder and who reported hazardous alcohol , cannabis and /or amphetamine use during the preceding month was recruited . Participants were r and omly allocated to motivational interviewing/CBT ( n = 65 ) or treatment as usual ( n = 65 ) , and were assessed on multiple outcomes at baseline , 15 weeks , 6 months and 12 months . RESULTS There was a short-term improvement in depression and a similar trend with regard to cannabis use among participants who received the motivational interviewing/CBT intervention , together with effects on general functioning at 12 months . There was no differential benefit of the intervention on substance use at 12 months , except for a potentially clinical ly important effect on amphetamine use . CONCLUSIONS The motivational interviewing/CBT intervention was associated with modest improvements This study evaluated the efficacy of adding contingency management techniques to vocational rehabilitation ( VR ) to improve treatment outcome as measured by entry into competitive employment . Nineteen dually diagnosed veterans who entered VR in the Veterans ' Administration 's compensated work therapy ( CWT ) program were r and omly assigned to CWT ( n = 8) or to CWT with enhanced incentives ( n = 11 ) . Over the first 16 weeks of rehabilitation , those in the incentives condition could earn up to dollar 1,006 in cash for meeting two sets of clinical goals : ( a ) remaining abstinent from drugs and alcohol and ( b ) taking steps to obtain and maintain a competitive job . Results indicate that relative to participants in the CWT-only group , those in the incentives condition engaged in more job- search activities , were more likely to remain abstinent from drugs and alcohol , were more likely to obtain competitive employment , and earned an average of 68 % more in wages . These results suggest that rehabilitation outcomes may be enhanced by restructuring traditional work-for-pay contingencies to include direct financial rewards for meeting clinical goals This study examined the effects of integrating mental health , substance abuse , and housing interventions for homeless persons with co-occurring severe mental illness and substance use disorder . With the use of a quasi-experimental design , integrated treatment was compared with st and ard treatment for 217 homeless , dually diagnosed adults over an 18-month period . The integrated treatment group had fewer institutional days and more days in stable housing , made more progress toward recovery from substance abuse , and showed greater improvement of alcohol use disorders than the st and ard treatment group . Abuse of drugs other than alcohol ( primarily cocaine ) improved similarly for both groups . Secondary outcomes , such as psychiatric symptoms , functional status , and quality of life , also improved for both groups , with minimal group differences favoring integrated treatment In adaptive treatment strategies , the treatment level and type is repeatedly adjusted according to ongoing individual response . Since past treatment may have delayed effects , the development of these treatment strategies is challenging . This paper advocates the use of sequential multiple assignment r and omized trials in the development of adaptive treatment strategies . Both a simple ad hoc method for ascertaining sample sizes and simple analysis methods are provided OBJECTIVE Comorbidity of substance abuse disorders with schizophrenia is associated with a greater risk for serious illness complications and poorer outcome . Method ologically sound studies investigating treatment approaches for patients with these disorders are rare , although recommendations for integrated and comprehensive treatment programs abound . This study investigates the relative benefit of adding an integrated psychological and psychosocial treatment program to routine psychiatric care for patients with schizophrenia and substance use disorders . METHOD The authors conducted a r and omized , single-blind controlled comparison of routine care with a program of routine care integrated with motivational interviewing , cognitive behavior therapy , and family or caregiver intervention . RESULTS The integrated treatment program result ed in significantly greater improvement in patients ' general functioning than routine care alone at the end of treatment and 12 months after the beginning of the study . Other benefits of the program included a reduction in positive symptoms and in symptom exacerbations and an increase in the percent of days of abstinence from drugs or alcohol over the 12-month period from baseline to follow-up . CONCLUSIONS These findings demonstrate the effectiveness of a program of routine care integrated with motivational interviewing , cognitive behavior therapy , and family intervention over routine psychiatric care alone for patients with comorbid schizophrenia and alcohol or drug abuse or dependence OBJECTIVES The feasibility and effectiveness of treating homeless mentally ill chemical abusers in community residences compared with a therapeutic community were evaluated . METHODS A total of 694 homeless mentally ill chemical abusers were r and omly referred to two community residences or a therapeutic community . All programs were enhanced to treat persons with dual diagnoses . Subjects ' attrition , substance use , and psychopathology were measured at two , six , and 12 months . RESULTS Forty-two percent of the 694 referred subjects were admitted to their assigned program and showed up for treatment , and 13 percent completed 12 months or more . Clients retained at both types of program showed reductions in substance use and psychopathology , but reductions were greater at the therapeutic community . Compared with subjects in the community residences , those in the therapeutic community were more likely to be drug free , as measured by urine analysis and self-reports , and showed greater improvement in psychiatric symptoms , as measured by the Center for Epidemiological Studies --Depression Scale and the Brief Psychiatric Rating Scale . Their functioning also improved , as measured by the Global Assessment of Functioning scale . CONCLUSIONS Homeless mentally ill chemical abusers who are retained in community-based residential programs , especially in therapeutic communities , can be successfully treated Homeless adults with both a serious mental illness and substance dependence ( N = 276 ) were r and omly assigned to : ( 1 ) a social model residential program providing integrated mental health and substance abuse treatment ; ( 2 ) a community-based nonresidential program using the same social model approach ; or ( 3 ) a control group receiving no intervention but free to access other community services . Interventions were design ed to provide 3 months of intensive treatment , followed by 3 months of nonresidential maintenance . Subjects completed baseline interviews prior to r and omization and reinterviews 3 , 6 , and 9 months later . Results showed that , while substance use , mental health , and housing outcomes improved from baseline , subjects assigned to treatment conditions differed little from control subjects . Examination of the relationship between length of treatment exposure and outcomes suggested that residential treatment had positive effects on outcomes at 3 months , but that these effects were eroded by 6 months BACKGROUND There is a well-recognized association between substance use and psychotic disorders , sometimes described as ' dual diagnosis ' . The use of substances by people with psychosis has a negative impact in terms of symptoms , longitudinal course of illness and psychosocial adjustment . There are few vali date d treatments for such individuals , and those that do exist are usually impracticable in routine clinical setting s. The present study employs a r and omized controlled experimental design to examine the effectiveness of a manualized group-based intervention in helping patients with dual diagnosis reduce their substance use . METHOD The active intervention consisted of weekly 90-min sessions over 6 weeks . The manualized intervention was tailored to participants ' stage of change and motivations for drug use . The control condition was a single educational session . RESULTS Sixty-three subjects participated , of whom 58 ( 92 % ) completed a 3-month follow-up assessment of psychopathology , medication and substance use . Significant reductions in favour of the treatment condition were observed for psychopathology , chlorpromazine equivalent dose of antipsychotics , alcohol and illicit substance use , severity of dependence and hospitalization . CONCLUSIONS It is possible to reduce substance use in individuals with psychotic disorders , using a targeted group-based approach . This has important implication s for clinicians who wish to improve the long-term outcome of their patients The effect of motivational interviewing on outpatient treatment adherence among psychiatric and dually diagnosed in patients was investigated . Subjects were 121 psychiatric in patients , 93 ( 77 % ) of whom had concomitant substance abuse/dependence disorders , who were r and omly assigned to : a ) st and ard treatment ( ST ) , including pharmacotherapy , individual and group psychotherapy , activities therapy , milieu treatment , and discharge planning ; or b ) ST plus motivational interviewing ( ST+MI ) , which involved 15 minutes of feedback on the results of a motivational assessment early in the hospitalization , and a 1-hour motivational interview just before discharge . Interviewers utilized motivational techniques described in Miller and Rollnick ( 1991 ) , such as reflective listening , discussion of treatment obstacles , and elicitation of motivational statements . Results indicated that the proportion of patients who attended their first outpatient appointment was significantly higher for the ST+MI group ( 47 % ) than for the ST group ( 21 % ; chi2 = 8.87 , df = 1 , p<.01 ) overall , and for dually diagnosed patients ( 42 % for ST+MI vs. 16 % for ST only ; chi2 = 7.68 , df = 1 , p<.01 ) . Therefore , brief motivational interventions show promise in improving outpatient treatment adherence among psychiatric and dually diagnosed patients OBJECTIVE Clients with co-occurring severe mental and substance use disorders are at high risk of institutionalization and other adverse outcomes . Although integrated mental health and substance abuse treatment is becoming a st and ard clinical approach for such clients , the optimal method for delivering integrated treatment remains unclear . METHOD This study compared integrated treatment delivered within two different models of community-based case management ( assertive community treatment and st and ard clinical case management ) . A total of 198 clients in two urban sites who had co-occurring disorders and were homeless or unstably housed were r and omly assigned to one of two treatment conditions and were followed for three years . RESULTS Participants in both treatment conditions improved over time in multiple outcome domains , and few differences were found between the two models . Decreases in substance use were greater than would be expected given time alone . At the site that had higher rates of institutionalization , clients who received st and ard case management were more likely to be institutionalized . However , in the site that had lower rates of institutionalization , no differences in the rate of institutionalization were found between the two treatment conditions . CONCLUSIONS Integrated treatment can be successfully delivered either by assertive community treatment or by st and ard clinical case management OBJECTIVE Uncertainty regarding the degree to which persons with schizophrenia may lack decision-making capacity , and what the predictors of capacity may be led us to examine the relationship between psychopathology , neurocognitive functioning , and decision-making capacity in a large sample of persons with schizophrenia at entry into a clinical trial . METHOD In the Clinical Antipsychotic Trials of Intervention Effectiveness ( CATIE ) schizophrenia trial , a clinical trial sponsored by the National Institute of Mental Health design ed to compare the effectiveness of antipsychotic drugs , subjects were administered the MacArthur Competence Assessment Tool- Clinical Research ( MacCAT-CR ) and had to demonstrate adequate decision-making capacity before r and omization . The MacCAT-CR , the Positive and Negative Syndrome Scale ( PANSS ) , and an extensive neurocognitive battery were Output:	Three types of interventions ( group counseling , contingency management , and residential dual diagnosis treatment ) show consistent positive effects on substance use disorder , whereas other interventions have significant impacts on other areas of adjustment ( e.g. , case management enhances community tenure and legal interventions increase treatment participation ) .
MS2969	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Vascular endothelial growth factor A ( VEGF-A ) is a potent cytokine that promotes angiogenesis and vascular permeability . After controlled ovarian stimulation ( COS ) for in vitro fertilization ( IVF ) , excessive VEGF-A production can occur , particularly in women with polycystic ovarian syndrome ( PCOS ) ; however , it is unclear whether the regulation of VEGF-A production is different between PCOS and non-PCOS women . OBJECTIVE The aim of this study was to determine whether there were differences in the dose- and time-dependent effects of insulin and IGFs on VEGF-A production by luteinized granulosa cells ( LGCs ) from women with and without PCOS . DESIGN AND SETTING A prospect i ve comparative experimental study was conducted at an institutional practice . PATIENTS Patients included six PCOS and six non-PCOS women undergoing COS and IVF . INTERVENTIONS Interventions included COS for IVF . MAIN OUTCOME MEASURES VEGF-A levels in culture media were collected daily for 3 d from LGCs after incubation with variable doses of insulin , IGF-I , and IGF-II in the presence and absence of LH . RESULTS In both study groups , exposure to LH alone did not alter VEGF-A levels . However , insulin or IGF increased VEGF-A levels within 1 d and appeared to synergize with LH at 3 d. VEGF-A production by non-PCOS LGCs was more sensitive to IGF exposure , whereas PCOS cells were more sensitive to insulin . Although an increase in DNA content ( P < 0.05 ) was noted in cultures of PCOS cells , progesterone levels were lower compared with non-PCOS LGCs . CONCLUSION Insulin and IGFs promote VEGF-A production in LGCs , but the response patterns are different when cells from PCOS and non-PCOS women are compared BACKGROUND The aim of this study was to determine whether , in polycystic ovarian syndrome ( PCOS ) patients , HCG action prolonged for 4 h improves the action of angiogenic substances [ ovarian renin angiotensin system and vascular endothelial growth factor ( VEGF ) ] , and consequently follicular maturation , oocyte quality and oocyte fertilization competence . METHODS In this prospect i ve study 20 patients with PCOS undergoing IVF were included . Oocyte retrieval was carried out either 34 or 38 h after HCG administration . Each follicle was analysed for prorenin , active renin , VEGF and estradiol . Oocytes were evaluated for quality ( mature , immature , degenerated oocytes ) , as were the embryos ( low or high ) . RESULTS In the HCG + 38 h group there were 245 follicles , and in the HCG + 34 h group 240 follicles . In the HCG + 38 h group , log active renin was lower ( 2.78 + /- 0.20 versus 2.91 + /- 0.25 ; P < 0.001 ) and VEGF higher ( 2276.0 + /- 790.1 versus 1946.6 + /- 954.5 pg/ml ; P < 0.001 ) . The odds ratio for obtaining oocytes from follicles was 1.6 [ 95 % confidence interval ( CI ) 1.1 - 2.6 ; P = 0.02 ] , and for developing high quality embryos 7.6 ( 95 % CI 2.8 - 20.9 ; P < 0.001 ) in favour of the HCG + 38 h group . CONCLUSIONS Follicular maturation and oocyte quality are related to the intrafollicular influences of active renin and VEGF in a time-dependent manner after HCG administration , whereas fertilization competence is related to VEGF only OBJECTIVE To determine the concentration of angiogenic factors ( vascular endothelial growth factor [ VEGF ] , basic fibroblast growth factor [ bFGF ] , and angiogenin ) in the follicular fluid ( FF ) and oocyte-cumulus complex culture medium ( CM ) of women undergoing IVF and to investigate the association of the concentrations with the maturity and fertilization of the oocyte . DESIGN Prospect i ve study . SETTING Academic tertiary-care institution . PATIENT(S ) IVF patients with unexplained or tubal factor infertility . INTERVENTION(S ) Analysis of VEGF , bFGF , and angiogenin FF and CM concentrations . MAIN OUTCOME MEASURE(S ) Oocyte maturity and fertilization and FF and CM angiogenic factor concentrations . RESULT ( S ) VEGF , bFGF , and angiogenin were determined in FF and CM . FF angiogenin concentrations were significantly higher when the oocyte was mature versus immature . CM VEGF concentrations were significantly higher when the oocyte was nonfertilized versus fertilized . Positive correlations were observed between angiogenic factors in CM . CONCLUSION ( S ) VEGF , bFGF , and angiogenin ( determined for the first time ) are secreted in the FF and CM . Elevated CM VEGF concentrations , probably implying oocyte-cumulus complex hypoxia , are negatively associated with oocyte fertilization . Elevated FF angiogenin concentrations are positively associated with oocyte maturity , possibly indicating angiogenin 's biological role beyond neovascularization To test the hypothesis that increased serum levels of vascular endothelial growth factor ( VEGF ) in women with polycystic ovaries or the polycystic ovary syndrome ( PCOS ) result from excess release by ovarian granulosa cells . Prospect i ve study . Academic research setting . Twenty women undergoing IVF treatment , of whom 10 had normal ovaries and 10 had polycystic ovaries . Human granulosa lutein cells were isolated from follicular fluid obtained on the day of oocyte retrieval . Release of VEGF was assessed after co-incubation of granulosa lutein cells with gonadotropins and insulin . Serum and follicular fluid concentrations of VEGF were measured . Release of VEGF from granulosa lutein cells and serum levels of VEGF . Incubation with human hCG , and luteinizing hormone increased release of VEGF into the culture medium . Insulin alone did not increase release of VEGF , but addition of insulin increased hCG-stimulated release of VEGF . Serum and follicular fluid VEGF concentrations and the amount VEGF released from granulosa lutein cells obtained from women with polycystic ovaries or PCOS and those who developed the ovarian hyperstimulation syndrome were greater than those from granulosa lutein cells obtained from women with normal ovaries and those who did not develop the ovarian hyperstimulation syndrome . The amount of VEGF released by granulosa lutein cells is gonadotropin dependent and is augmented by insulin . The increased circulating concentrations of VEGF in women with PCOS may not only be due to an increased number of actively secreting granulosa lutein cells but also due to increased secretory capacity of each granulosa cell The multicentric study regroups 128 cases of the ovarian hyperstimulation syndrome ( OHSS ) in in-vitro fertilization ( IVF ) and 256 selected controls . Values of serum oestradiol obtained from different laboratories were found to be normally distributed after logarithmic transformation . Comparative study of clinical and biological characteristics indicates that among OHSS patients ( i ) mean age was lower ; ( ii ) tubal indications for IVF were less frequent ; ( iii ) polycystic ovary-like conditions ( i.e. hyper and rogenism , anovulation , luteinizing hormone/follicle stimulating hormone ratio > 2 ) were more frequent . OHSS patients displayed ovarian hypersensitivity reflected by higher oestradiol peak concentrations in response to lower dosage of human menopausal gonadotrophin and by a steeper slope of oestradiol increment during stimulation . In these patients , the collection of greater numbers of fertilizable oocytes allowed replacement of more embryos with a good vitality score . Ongoing pregnancy rate was found to be higher among the OHSS patients . The following complications were recorded among OHSS cases : abdominal fluid at echographic examination or clinical ascites ( 86.7 and 71.1 % , respectively ) ; pleural and pericardial effusion ( 21 and 3 % , respectively ) ; haemoconcentration ( 71.1 % ) ; electrolytic disorders ( 6.2 % ) . Although significantly different between groups , clinical and biological parameters under study showed considerable overlap of their distributions in control and OHSS cases . Therefore , these data must be su bmi tted to discriminant analysis in order to derive a formula predictive of the risk of OHSS OBJECTIVE To study the serum levels and correlation of vascular endothelial growth factor ( VEGF ) , insulin-like growth factor 1 ( IGF-1 ) , hormonal profile , and Doppler blood flow changes within the ovarian stroma before and after laparoscopic ovarian drilling ( LOD ) in women with clomiphene-resistant polycystic ovary syndrome ( PCOS ) . DESIGN Prospect i ve controlled study . SETTING University teaching hospital . PATIENT(S ) Twenty-five women with clomiphene-resistant PCOS ( group 1 ) and 20 women with regular menstrual cycles as a comparison group ( group 2 ) . INTERVENTION(S ) Laparoscopic ovarian drilling . MAIN OUTCOME MEASURE(S ) Serum levels of VEGF , IGF-1 , and Doppler indices of ovarian stromal blood flow . RESULT ( S ) The serum levels of VEGF , IGF-1 , T , and LH were significantly higher in group 1 before LOD than in group 2 . The Doppler indices ( pulsatility index and resistance index ) of ovarian stromal blood flow were also significantly lower in group 1 before LOD than in group 2 . The serum levels of VEGF , T , and LH were significantly reduced in group 1 after LOD compared with in group 1 before LOD . Doppler indices ( pulsatility index and resistance index ) of ovarian stromal blood flow were significantly increased after LOD . The VEGF levels before LOD were positively correlated with IGF-1 , LH , and T. After LOD , the VEGF levels were positively correlated with LH and T. CONCLUSION ( S ) Higher serum levels of VEGF and IGF-1 may explain the increased vascularity that was demonstrated by Doppler blood flow measurements in PCOS . Laparoscopic ovarian drilling reduced serum VEGF , IGF-1 , T , and LH and reduced ovarian blood flow velocities , which may explain the reduction of ovarian hyperstimulation syndrome in women with PCOS after LOD OBJECTIVE To evaluate the serum vascular endothelial growth factor concentrations and insulin responses to the oral glucose tolerance test before and after laparoscopic ovarian drilling in women with PCOS . DESIGN Prospect i ve study . SETTING University teaching center . PATIENT(S ) Twenty-seven women with clomiphene citrate-resistant polycystic ovary syndrome . INTERVENTION(S ) Laparoscopic ovarian drilling . MAIN OUTCOME MEASURE(S ) VEGF levels and insulin responses to OGTT before and after ovarian drilling . RESULT ( S ) No difference was found in VEGF levels in women with PCOS before ( 6.0 + /- 1.2 ng/mL ) and after ovarian drilling ( 5.5 + /- 1.2 ng/mL ) . VEGF levels before and after ovarian drilling in women who conceived were , respectively , 5.9 + /- 1.0 and 5.1 + /- 0.9 ng/mL and in those who did not conceive were 6.0 + /- 1.3 and 5.7 + /- 1.2 ng/mL. No correlation was found between baseline serum insulin and VEGF levels . VEGF concentrations in women with normal ovaries ( 4.5 + /- 1.7 ng/mL ) were significantly lower than in women with PCOS . There was no difference in glucose and insulin responses to OGTT before and after ovarian drilling . CONCLUSION ( S ) VEGF levels in women with PCOS are higher than in normal women , and ovarian drilling does not affect these levels . The procedure does not change insulin responses to OGTT The aim of this study was to determine whether follicular oestradiol and vascular endothelial growth factor ( VEGF ) concentrations in women with polycystic ovarian syndrome ( PCOS ) differ according to the use of gonadotrophin-releasing hormone ( GnRH ) antagonists or GnRH agonists . Furthermore , the effect of follicular oestradiol and VEGF concentrations on oocyte and embryo quality was investigated . In this prospect i ve clinical study , 20 women with PCOS undergoing intracytoplasmic sperm injection for male factor infertility were included using a GnRH antagonist or a GnRH agonist protocol . In each follicle , oestradiol and VEGF concentrations were determined . In the GnRH antagonist group 254 follicles and in the GnRH Output:	This review concluded that VEGF may have a strategic role in the pathophysiology of PCOS and is the key mediator in the pathogenesis of ovarian hyperstimulation syndrome ( OHSS ) in women undergoing assisted reproductive procedures .
MS2970	*TASK* the task is to summarize an input biomedical literature in six sentences *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 clinical trial . OBJECTIVE To compare the effectiveness of 2 physical therapy treatment approaches for impingement syndrome of the shoulder . BACKGROUND Manual physical therapy combined with exercise is a commonly applied but currently unproven clinical treatment for impingement syndrome of the shoulder . METHODS AND MEASURES Thirty men and 22 women ( age 43 years + /- 9.1 ) diagnosed with shoulder impingement syndrome were r and omly assigned to 1 of 2 treatment groups . The exercise group performed supervised flexibility and strengthening exercises . The manual therapy group performed the same program and received manual physical therapy treatment . Both groups received the selected intervention 6 times over a 3-week period . The testers , who were blinded to group assignment , measured strength , pain , and function before treatment and after 6 physical therapy visits . Strength was a composite score of isometric strength tests for internal rotation , external rotation , and abduction . Pain was a composite score of visual analog scale measures during resisted break tests , active abduction , and functional activities . Function was measured with a functional assessment question naire . The visual analog scale used to measure pain with functional activities and the functional assessment question naire were also measured 2 months after the initiation of treatment . RESULTS Subjects in both groups experienced significant decreases in pain and increases in function , but there was significantly more improvement in the manual therapy group compared to the exercise group . For example , pain in the manual therapy group was reduced from a pretreatment mean ( + /- SD ) of 575.8 ( + /- 220.0 ) to a posttreatment mean of 174.4 ( + /- 183.1 ) . In contrast , pain in the exercise group was reduced from a pretreatment mean of 557.1 ( + /- 237.2 ) to a posttreatment mean of 360.6 ( + /- 272.3 ) . Strength in the manual therapy group improved significantly while strength in the exercise group did not . CONCLUSION Manual physical therapy applied by experienced physical therapists combined with supervised exercise in a brief clinical trial is better than exercise alone for increasing strength , decreasing pain , and improving function in patients with shoulder impingement syndrome This paper provides an up-to- date overview of the occurrence , diagnosis , risk factors , prognostic indicators and outcome of shoulder disorder ( SD ) , and of the validity and reproducibility of diagnostic classifications and diagnostic imaging techniques for SD . Furthermore , the available evidence on the effectiveness of non-steroidal anti-inflammatory drugs ( NSAIDs ) , corticosteroid injections and physiotherapy for SD is summarized on the basis of r and omized controlled trials with an acceptable quality of their methods . The annual incidence of SD is estimated at about 7 % , its 1-year period prevalence at about 51 % and its lifetime prevalence at about 10 % . While approximately 50 % of all patients with SD seek medical care , about 95 % are treated in primary health care . Of all new episodes of SD presenting to primary care , approximately 50 % seem to resolve within 6 months , while about 40 % seem to persist for up to 12 months . Several prognostic indicators for a favourable or a poor outcome of SD have been identified , but a comprehensive prognostic model is not available . While evidence for the prognostic validity of popular diagnostic classifications of SD is lacking , their reproducibility has been shown to be poor . The accuracy and clinical usefulness of diagnostic imaging techniques appear to be sufficiently verified for SD in secondary care , while their clinical usefulness in primary care and prognostic validity are not . NSAIDs and steroid injections for SD have been shown to be effective within 6 weeks , but their effect on long-term outcome remains unclear . There is very limited evidence for the effectiveness in SD of physiotherapy , including exercise therapy , ultrasound , electrotherapy , laser , mobilization and manipulation This paper reports a prospect i ve study of 72 consecutive patients with fractures or fracture-dislocations of the upper end of the humerus , treated during 1981 . Most were elderly and treatment was conservative . Of the 72 patients 64 were followed up for a period of six months . Observations were made on the type of fracture , the speed and pattern of recovery of shoulder movements , on the time of commencement of physiotherapy , and on its duration . We found that with conservative treatment alone , 94 % of our patients had good or satisfactory results at six months from injury . The criteria for manipulation are discussed and the literature is review ed Current knowledge of the clinical course and efficacy of treatment for shoulder pain comes mainly from studies of hospital patients . However , only a few patients experiencing such pain require referral to a specialist . Although shoulder pain is common in the general population , the outcome of patients presenting in general practice is unknown.1 We conducted a prospect i ve cohort study to determine the outcome of shoulder pain in primary care . Twelve general practitioners recruited 166 patients who consulted with a new episode of shoulder pain during one year . They recorded demographic information , diagnosis , management , and an assessment of passive elevation of the shoulder ; patients assessed the disability associated with their symptoms with a vali date d 22 item disability question naire.2 To assess outcome , identical disability question naires were sent to patients six and 18 months after consultation , together with a question measuring self assessed change in symptoms Primary shoulder impingement syndrome is a common shoulder problem which , if treated ineffectively , can lead to more serious pathology and expensive treatment . This study examined whether subjects receiving joint mobilization and comprehensive treatment ( hot packs , active range of motion , physiologic stretching , muscle strengthening , soft tissue mobilization , and patient education ) would have improved pain , mobility , and function compared with similar patients receiving comprehensive treatment alone . Subjects were eight men and six women ( mean age = 52.9 years ) with primary shoulder impingement syndrome ( superolateral shoulder pain , decreased active humeral elevation , limited overhead function ) . Following r and om assignment to experimental ( N = 7 ) and control groups ( N = 7 ) , three blinded evaluators tested 24-hour pain ( visual analog scale ) , pain with subacromial compression test ( visual analog scale ) , active range of motion ( goniometry ) , and function ( reaching forward , behind the head , and across the body in an overhead position ) before and after nine treatments . One-tailed analyses of covariance ( baseline values as covariates ) showed that the experimental group had less 24-hour pain and pain with subacromial compression test but no differences in range of motion and function ( Mann-Whitney U ) compared with controls . The experimental group improved on all variables , while the control group improved only on mobility and function ( one-tailed , paired t tests ; Wilcoxon matched pairs ) . Age , side of dominance , duration of symptoms , treatment attendance , exercise quality , and adherence had no effect on the outcomes . Results may be affected by inadequate sample size , minimal capsular tightness , insensitive functional scale , nonspecific motion measurements , position at which mobilization treatment was given , or a strong effect of comprehensive treatment . Mobilization decreased 24-hour pain and pain with subacromial compression test in patients with primary shoulder impingement syndrome , but larger replication studies are needed to assess more clearly mobilization 's influence on motion and function OBJECTIVE To determine the natural history of shoulder pain in the population , and predictors of outcome on the basis of clinical and individual factors . In addition , to determine whether outcome is influenced by the definition of shoulder pain used . METHODS A prospect i ve cohort study , over a 3 year period , of subjects recruited from a cross sectional population screening study of shoulder pain , conducted in the Greater Manchester area of the UK . RESULTS Of 92 subjects classified as having shoulder pain in the cross sectional study , 50 ( 54 % ) reported shoulder pain at followup about 3 years later . In 90 % of cases this was accompanied by some disability specifically relating to the symptoms . Baseline factors that predicted symptoms at followup were : pain ( indicated on a manikin ) within a more narrowly defined shoulder region , shoulder pain related disability , pain on the day of examination , symptoms lasting more than one year , and a high score on the General Health Question naire , a measure of psychological distress . CONCLUSION Shoulder pain in the population is a longterm disabling symptom , although many subjects do not seek early medical consultation . Disability ( independent of whether there was restriction of movement on examination ) is a strong predictor of continuing symptoms . The outcome observed in epidemiological studies of shoulder pain will be influenced by the initial definition of symptoms Abstract Relatively little is known about outcomes following clinical osteoporotic fractures at nonhip , nonvertebral skeletal sites . To address this issue , we prospect ively assessed post-fracture disability at multiple skeletal sites in a population of 909 older ( aged 55–81 years ) , community-dwelling women with low femoral neck bone mineral density who had experienced a fracture while enrolled in the Fracture Intervention Trial ( FIT ) . FIT is a r and omized , double-masked , placebo-controlled trial that was design ed to determine the effect of alendronate on fracture incidence , and the current study was conducted as a secondary analysis of FIT data . Following incident clinical fractures , FIT participants were followed prospect ively for assessment of site-specific , fracture-related disability . Measures of disability were self-reported days hospitalized or confined to bed because of the fracture ( ` bed days ' ) and days of reduced usual activities because of the fracture ( ` limited activity days ' ) . Of fracture types evaluated , those of the hip result ed in the highest percentage of subjects with any bed days or limited activity days after fracture ( 94 % with any bed days and 100 % with any limited activity days ) , though the mean number of bed days and limited activity days appeared highest after lumbar vertebral fractures ( 25.8 mean bed days and 158.5 mean limited activity days ) . Substantial disability also was reported after fractures of thoracic vertebrae , humerus , distal forearm , ankle and foot . Within fracture types , post-fracture disability was highly variable , ranging from none to more than 6 months BACKGROUND AND PURPOSE The aim of this study was to evaluate the efficacy of a physical therapy approach to the treatment of shoulder pain . Subjects . Sixty-six volunteers with shoulder pain believed to be of local mechanical origin were r and omly allocated to either a treatment group or a control group . METHODS Subjects in the treatment group received 1 month of physical therapy aim ed at restoring function of their shoulder muscles . Subjects in the control group received no treatment . Outcome measurements of pain intensity , range of motion ( ROM ) , isometric muscle force , functional impairment , and self-perception of improvement were obtained by blinded assessment . RESULTS Subjects in the treatment group showed improvement in pain-free abduction and flexion ROM , functional impairment , and self-perception of improvement . The control group deteriorated slightly over the experimental period in ROM and functional impairment measures . CONCLUSION AND DISCUSSION These results suggest that the physical therapy approach used in this study is effective in improving shoulder function in subjects experiencing pain of mechanical origin . The results also provide little evidence of spontaneous recovery over a 1-month period The effectiveness of arthroscopic surgery , supervised exercises , and placebo was compared in 125 patients with rotator cuff disease ( impingement syndrome stage II ) in a r and omized clinical trial . The median age was 48 years , and the median duration of complications was 1 to 2 years . The treatments were arthroscopic subacromial decompression performed by 2 experienced surgeons , an exercise regimen supervised for 3 to 6 months by 1 experienced physiotherapist , or 12 sessions of detuned soft laser ( placebo ) for 6 weeks . The criterion for success was a Neer shoulder score > 80 . Fifteen ( 50 % ) and 11 ( 22 % ) of the patients r and omized to placebo and exercises , respectively , had surgery during the 2 1/2-year follow-up period and were classified as having failure with the treatments . The success rate was higher ( P < .01 ) for patients r and omized to surgery ( 26 of 38 ) and exercises ( 27 of 44 ) compared with the placebo group ( 7 of 28 ) . The odds ratio for success after surgery compared with exercises was 1.5 ( 95 % confidence interval 0.6 to 3.7 ; P = .49 ) . Including all patients who underwent operation , the success rate in those not on sick leave ( 19 of 21 ) before surgery was higher compared with those on sick leave ( 18 of 36 ) ( adjusted odds ratio 5.6 [ 1.2 to 29.2 ] ) . Similar results were observed for patients not receiving versus those receiving regular pain medication before surgery ( adjusted odds ratio 4.2 [ 1.2 to 15.8 ] ) A poor outcome arising from a minimally displaced fracture of the neck of the humerus may be the result of a contracture of the capsule of the glenohumoral joint . Pulsed high frequency electromagnetic energy ( PHFE ) is an electrotherapy to reduce pain and swelling and to enhance healing . If PHFE is effective , early mobilization of the injured shoulder will be possible , reducing the risk of joint capsule contracture . We therefore conducted a double-blind trial of PHFE in minimally displaced fractures of the neck of the humerus . Early physiotherapy produced an excellent outcome in all cases . The functional outcome depended on age rather than time of starting treatment , although a relationship was found between the time of starting treatment and the duration of therapy required . The use of PHFE did not improve the result further We undertook a prospect i ve , controlled trial which compared two rehabilitation programmes for 86 patients who sustained two-part fractures of the proximal humerus . Patients were r and omised either to receive immediate physiotherapy within one week ( group A ) or delayed physiotherapy after three Output:	Electrotherapy or hydrotherapy does not enhance recovery and joint mobilization has limited evidence of its efficacy . The best available evidence for shoulder rehabilitation emphasizes using advice , exercise , and mobilization of limited joints to restore upper limb function . Placing controlled stresses throughout the fracture site at an early stage will optimize bone repair without increasing complication rates . This approach requires cooperation between the referring surgeon and therapist and will optimize the patient 's shoulder function and maintain their functional independence .
MS2971	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objective . To assess the efficacy of rituximab ( RTX ) in SSc . Methods . Fourteen patients with SSc were evaluated . Eight patients were r and omized to receive two cycles of RTX at baseline and 24 weeks [ each cycle consisted of four weekly RTX infusions ( 375 mg/m2 ) ] in addition to st and ard treatment , whereas six patients ( control group ) received st and ard treatment alone . Lung involvement was assessed by pulmonary function tests ( PFTs ) and chest high-resolution CT ( H RCT ) . Skin involvement was assessed both clinical ly and histologically . Results . There was a significant increase of forced vital capacity ( FVC ) in the RTX group compared with baseline ( mean ± s.d . : 68.13 ± 19.69 vs 75.63 ± 19.73 , at baseline vs 1-year , respectively , P = 0.0018 ) . The median percentage of improvement of FVC in the RTX group was 10.25 % , whereas that of deterioration in the controls was 5.04 % ( P = 0.002 ) . Similarly , diffusing capacity of carbon monoxide ( DLCO ) increased significantly in the RTX group compared with baseline ( mean ± s.d . : 52.25 ± 20.71 vs 62 ± 23.21 , at baseline vs 1-year respectively , P = 0.017 ) . The median percentage of improvement of DLCO in the RTX group was 19.46 % , whereas that of deterioration in the control group was 7.5 % ( P = 0.023 ) . Skin thickening , assessed with the Modified Rodnan Skin Score ( MRSS ) , improved significantly in the RTX group compared with the baseline score ( mean ± s.d . : 13.5 ± 6.84 vs 8.37 ± 6.45 at baseline vs 1-year , respectively , P < 0.001 ) . Conclusion . Our results indicate that RTX may improve lung function in patients with SSc . To confirm our encouraging results we propose that larger scale , multicentre studies with longer evaluation periods are needed Objectives ( 1 ) Hypothesis testing of the potency of rituximab ( RTX ) in preventing fibrotic complications and ( 2 ) assessing acceptability and feasibility of RTX in early systemic sclerosis ( SSc ) . Methods A small , 24-month , r and omised , double-blind , placebo-controlled , single-centre trial in patients with SSc diagnosed < 2 years was conducted . Patients received RTX or placebo infusions at t=0 , t=15 days and t=6 months . Patients were clinical ly evaluated every 3 months , with lung function tests and high-resolution CT every other visit . Skin biopsies were taken at baseline and month 3 . Immunophenotyping of peripheral blood mononuclear cells was performed at every visit , except at months 9 and 18 . Adverse events , course of skin and pulmonary involvement and B cell population s in skin and peripheral blood were evaluated . Results In total 16 , patients ( rituximab n=8 , placebo n=8 ) were included . Twelve patients had diffuse cutaneous SSc . Eighty-eight adverse events ( RTX n=53 , placebo n=35 , p=0.22 ) and 11 serious adverse events ( RTX n=7 , placebo n=4 , p=0.36 ) occurred . No unexpected RTX-related events were observed . Mean skin score over time did not differ between the groups . Over time , forced vital capacity and extent of lung involvement slightly improved with RTX , but this difference was insignificant . In peripheral blood B cells depletion was demonstrated . Conclusions No unexpected safety issues were observed with RTX in early SSc . Although this small trial could not confirm or reject potential efficacy of RTX in these patients , future placebo-controlled trials are warranted , specifically in the subgroup of patients with pulmonary involvement . Trial registration number EudraCT 2008 - 07180 - 16 ; Results OBJECTIVE B cells are likely to contribute to the pathogenesis of systemic lupus erythematosus ( SLE ) , and rituximab induces depletion of B cells . The Exploratory Phase II/III SLE Evaluation of Rituximab ( EXPLORER ) trial tested the efficacy and safety of rituximab versus placebo in patients with moderately-to-severely active extrarenal SLE . METHODS Patients entered with > or=1 British Isles Lupus Assessment Group ( BILAG ) A score or > or=2 BILAG B scores despite background immunosuppressant therapy , which was continued during the trial . Prednisone was added and subsequently tapered . Patients were r and omized at a ratio of 2:1 to receive rituximab ( 1,000 mg ) or placebo on days 1 , 15 , 168 , and 182 . RESULTS In the intent-to-treat analysis of 257 patients , background treatment was evenly distributed among azathioprine , mycophenolate mofetil , and methotrexate . Fifty-three percent of the patients had > or=1 BILAG A score at entry , and 57 % of the patients were categorized as being steroid dependent . No differences were observed between placebo and rituximab in the primary and secondary efficacy end points , including the BILAG-defined response , in terms of both area under the curve and l and mark analyses . A beneficial effect of rituximab on the primary end point was observed in the African American and Hispanic subgroups . Safety and tolerability were similar in patients receiving placebo and those receiving rituximab . CONCLUSION The EXPLORER trial enrolled patients with moderately-to-severely active SLE and used aggressive background treatment and sensitive cutoffs for nonresponse . No differences were noted between placebo and rituximab in the primary and secondary end points . Further evaluation of patient subsets , biomarkers , and exploratory outcome models may improve the design of future SLE clinical trials Objective . The aim was to assess the efficacy of rituximab for the cutaneous manifestations of adult DM and JDM . Methods . Patients with refractory adult DM ( n = 72 ) and JDM ( n = 48 ) were treated with rituximab in a r and omized placebo-phase-controlled trial [ either rituximab early drug ( week 0/1 ) or rituximab late arms ( week 8/9 ) , such that all subjects received study drug ] . Stable concomitant therapy was allowed . Cutaneous disease activity was assessed using the Myositis Disease Activity Assessment Tool , which grade s cutaneous disease activity on a visual analog scale . A myositis damage assessment tool , termed the Myositis Damage Index , was used to assess cutaneous damage . Improvement post-rituximab was evaluated in individual rashes as well as in cutaneous disease activity and damage scores . The & khgr;2 test , Student ’s paired t-test and Wilcoxon test were used for analysis . Results . There were significant improvements in cutaneous disease activity from baseline to the end of the trial after rituximab administration in both adult DM and JDM subsets . The cutaneous visual analog scale activity improved in adult DM ( 3.22–1.72 , P = 0.0002 ) and JDM ( 3.26–1.56 , P < 0.0001 ) , with erythroderma , erythematous rashes without secondary changes of ulceration or necrosis , heliotrope , Gottron sign and papules improving most significantly . Adult DM subjects receiving rituximab earlier in the trial demonstrated a trend for faster cutaneous response ( 20 % relative improvement from baseline ) compared with those receiving B cell depletion later ( P = 0.052 ) . Conclusion . Refractory skin rashes in adult DM and JDM showed improvement after the addition of rituximab to the st and ard therapy in a clinical trial Introduction An over-expression of CD19 has been shown in B cells of systemic sclerosis ( SSc ) and B cells are thought to contribute to the induction of skin fibrosis in the tight skin mouse model . The aim was to define the outcome on safety and the change in skin score after rituximab therapy in SSc patients and to correlate the clinical characteristics with the levels of interleukin (IL)-6 and with the immune cell infiltrate detected by immunohistochemistry . Methods Nine patients with SSc with mean age 40.9 ± 11.1 years were treated with anti-CD20 , 1 g at time 0 and after 14 days . Skin biopsy was performed at baseline and during the follow-up . B-cell activating factor ( BAFF ) and IL-6 levels were also determined at the follow-up times . Results After 6 months patients presented a median decrease of the skin score of 43.3 % ( range 21.1 - 64.0 % ) , and a decrease in disease activity index and disease severity index . IL-6 levels decreased permanently during the follow up . After treatment , a complete depletion of peripheral blood B cells was observed in all but 2 patients . Only 3 patients presented CD20 positive cells in the biopsy of the involved skin at baseline . Conclusions Anti-CD20 treatment has been well tolerated and SSc patients experienced an improvement of the skin score and of clinical symptoms . The clear fall in IL-6 levels could contribute to the skin fibrosis improvement , while the presence of B cells in the skin seems to be irrelevant with respect to the outcome after B cell depletion . Trial registration IS RCT N77554566 OBJECTIVE To study the efficacy and safety of B cell depletion with rituximab , a chimeric murine/human anti-CD20 monoclonal antibody , in patients with primary Sjögren 's syndrome ( SS ) in a double-blind , r and omized , placebo-controlled trial . METHODS Patients with active primary SS , as determined by the revised American-European Consensus Group criteria , and a rate of stimulated whole saliva secretion of > or = 0.15 ml/minute were treated with either rituximab ( 1,000 mg ) or placebo infusions on days 1 and 15 . Patients were assigned r and omly to a treatment group in a ratio of 2:1 ( rituximab : placebo ) . Followup was conducted at 5 , 12 , 24 , 36 , and 48 weeks . The primary end point was the stimulated whole saliva flow rate , while secondary end points included functional , laboratory , and subjective variables . RESULTS Thirty patients with primary SS ( 29 female ) were r and omly allocated to a treatment group . The mean + /- SD age of the patients receiving rituximab was 43 + /- 11 years and the disease duration was 63 + /- 50 months , while patients in the placebo group were age 43 + /- 17 years and had a disease duration of 67 + /- 63 months . In the rituximab group , significant improvements , in terms of the mean change from baseline compared with that in the placebo group , were found for the primary end point of the stimulated whole saliva flow rate ( P = 0.038 versus placebo ) and also for various laboratory parameters ( B cell and rheumatoid factor [ RF ] levels ) , subjective parameters ( Multidimensional Fatigue Inventory [ MFI ] scores and visual analog scale [ VAS ] scores for sicca symptoms ) , and extragl and ular manifestations . Moreover , in comparison with baseline values , rituximab treatment significantly improved the stimulated whole saliva flow rate ( P = 0.004 ) and several other variables ( e.g. , B cell and RF levels , unstimulated whole saliva flow rate , lacrimal gl and function on the lissamine green test , MFI scores , Short Form 36 health survey scores , and VAS scores for sicca symptoms ) . One patient in the rituximab group developed mild serum sickness-like disease . CONCLUSION These results indicate that rituximab is an effective and safe treatment strategy for patients with primary SS In the United States , approximately 35 % of adults with Systemic Lupus Erythematosus ( SLE ) have clinical evidence of nephritis at the time of diagnosis ; with an estimated total of 50–60 % developing nephritis during the first 10 years of disease [ 1–4 ] . The prevalence of nephritis is significantly higher in African Americans and Hispanics than in Caucasians , and is higher in men than in women . Renal damage is more likely to develop in non-Caucasian groups [ 2–4 ] . Overall survival in patients with SLE is approximately 95 % at 5 years after diagnosis and 92 % at 10 years [ 5 , 6 ] . The presence of lupus nephritis significantly reduces survival , to approximately 88 % at 10 years , with even lower survival in African Americans [ 5 , 6 ] . The American College of Rheumatology ( ACR ) last published guidelines for management of systemic lupus erythematosus ( SLE ) in 1999 [ 7 ] . That publication was design ed primarily for education of primary care physicians and recommended therapeutic and management approaches for many manifestations of SLE . Recommendations for management of lupus nephritis ( LN ) consisted of pulse glucocorticoids followed by high dose daily glucocorticoids in addition to an immunosuppressive medication , with cyclophosphamide viewed as the most effective immunosuppressive medication for diffuse proliferative glomerulonephritis . Mycophenolate mofetil was not yet in use for lupus nephritis and was not mentioned . Since that time , many clinical trials of glucocorticoids-plus-immunosuppressive interventions have been published , some of which are high quality prospect i ve trials , and some not only prospect i ve Output:	Evidence supports the use of rituximab in moderate-to-severe refractory systemic lupus erythematosus , diffuse skin involvement in systemic sclerosis and systemic involvement in primary Sjögren syndrome . In addition , there is a consensus about the use of rituximab in refractory myositis . Conclusion : Rituximab is a treatment option in several SARDs .
MS2972	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Of the 200 million adults worldwide who undergo noncardiac surgery each year , more than 1 million will die within 30 days . OBJECTIVE To determine the relationship between the peak fourth-generation troponin T ( TnT ) measurement in the first 3 days after noncardiac surgery and 30-day mortality . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve , international cohort study that enrolled patients from August 6 , 2007 , to January 11 , 2011 . Eligible patients were aged 45 years and older and required at least an overnight hospital admission after having noncardiac surgery . MAIN OUTCOME MEASURES Patients ' TnT levels were measured 6 to 12 hours after surgery and on days 1 , 2 , and 3 after surgery . We undertook Cox regression analysis in which the dependent variable was mortality until 30 days after surgery , and the independent variables included 24 preoperative variables . We repeated this analysis , adding the peak TnT measurement during the first 3 postoperative days as an independent variable and used a minimum P value approach to determine if there were TnT thresholds that independently altered patients ' risk of death . RESULTS A total of 15,133 patients were included in this study . The 30-day mortality rate was 1.9 % ( 95 % CI , 1.7%-2.1 % ) . Multivariable analysis demonstrated that peak TnT values of at least 0.02 ng/mL , occurring in 11.6 % of patients , were associated with higher 30-day mortality compared with the reference group ( peak TnT ≤ 0.01 ng/mL ) : peak TnT of 0.02 ng/mL ( adjusted hazard ratio [ aHR ] , 2.41 ; 95 % CI , 1.33 - 3.77 ) ; 0.03 to 0.29 ng/mL ( aHR , 5.00 ; 95 % CI , 3.72 - 6.76 ) ; and 0.30 ng/mL or greater ( aHR , 10.48 ; 95 % CI , 6.25 - 16.62 ) . Patients with a peak TnT value of 0.01 ng/mL or less , 0.02 , 0.03 - 0.29 , and 0.30 or greater had 30-day mortality rates of 1.0 % , 4.0 % , 9.3 % , and 16.9 % , respectively . Peak TnT measurement added incremental prognostic value to discriminate those likely to die within 30 days for the model with peak TnT measurement vs without ( C index = 0.85 vs 0.81 ; difference , 0.4 ; 95 % CI , 0.2 - 0.5 ; P < .001 for difference between C index values ) . The net reclassification improvement with TnT was 25.0 % ( P < .001 ) . CONCLUSION Among patients undergoing noncardiac surgery , the peak postoperative TnT measurement during the first 3 days after surgery was significantly associated with 30-day mortality BACKGROUND Cardiac complications are important causes of morbidity after noncardiac surgery . The purpose of this prospect i ve cohort study was to develop and vali date an index for risk of cardiac complications . METHODS AND RESULTS We studied 4315 patients aged > or = 50 years undergoing elective major noncardiac procedures in a tertiary-care teaching hospital . The main outcome measures were major cardiac complications . Major cardiac complications occurred in 56 ( 2 % ) of 2893 patients assigned to the derivation cohort . Six independent predictors of complications were identified and included in a Revised Cardiac Risk Index : high-risk type of surgery , history of ischemic heart disease , history of congestive heart failure , history of cerebrovascular disease , preoperative treatment with insulin , and preoperative serum creatinine > 2.0 mg/dL. Rates of major cardiac complication with 0 , 1 , 2 , or > or = 3 of these factors were 0.5 % , 1.3 % , 4 % , and 9 % , respectively , in the derivation cohort and 0.4 % , 0.9 % , 7 % , and 11 % , respectively , among 1422 patients in the validation cohort . Receiver operating characteristic curve analysis in the validation cohort indicated that the diagnostic performance of the Revised Cardiac Risk Index was superior to other published risk-prediction indexes . CONCLUSIONS In stable patients undergoing nonurgent major noncardiac surgery , this index can identify patients at higher risk for complications . This index may be useful for identification of c and i date s for further risk stratification with noninvasive technologies or other management strategies , as well as low-risk patients in whom additional evaluation is unlikely to be helpful OBJECTIVES To determine if troponin I and NT-proBNP were predictors of 6-month mortality after emergency orthopedic-geriatric surgery in a frail population . DESIGN Prospect i ve observational study . SETTING Orthopedic-geriatric unit of a metropolitan hospital in Australia . PARTICIPANTS A total of 383 patients were screened ; 44 were eligible for this study of which 33 patients consented who were receiving high-level care or had severe dementia or an illness with a prognosis of less than 12 months . MEASUREMENTS Troponin I and NT-proBNP were tested on one preoperative sample and at least one postoperative blood sample . Cardiac events were defined as acute myocardial infa rct ion , congestive cardiac failure , new onset or rapid atrial fibrillation , major arrhythmia , or cardiac arrest . RESULTS The mean age of the patients was 85.8 + /- 9.6 years and 93.9 % had a fractured neck of femur . Premorbid cardiac conditions were common ( 24.2 % had ischemic heart disease and 21.2 % congestive cardiac failure ) . A third of patients had a preoperative troponin elevation and 60.6 % had a postoperative elevation . The mortality within 30 days of surgery was 15.2 % ( 5/33 patients ) , rising to 39.4 % ( 13/33 ) at 6 months with 46.2 % ( 6/13 ) dying of a cardiac cause . The Kaplan-Meier survival curve was not significantly different between patients with and without a troponin elevation . A third of patients sustained a cardiac event at 6 months . The median preoperative NT-proBNP was 1651.50 pg/L , range 25 to 31,227 , and median postoperative NT-proBNP was 3038.50pg/L , range 44 to 27,348 . Troponin I and NT pro-BNP did not predict 6-month mortality or cardiac complications . Predictors of 6-month mortality using univariate analysis were number of comorbidities OR 2.0 ( 95 % CI 1.1 - 3.8 , P = .033 ) and premorbid atrial fibrillation OR 7.7 ( 95 % CI 1.2 - 47.8 , P = .028 ) . CONCLUSION Troponin I and NT-proBNP were not predictors of 6-month mortality or cardiac events in an older frailer population of patients undergoing orthopedic surgery . These patients sustained substantial cardiac morbidity and mortality at 6 months after surgery . The control of symptoms , rather than prolongation of life with cardiological intervention , may be more appropriate for this patient group : The purpose of this up date of the European Society of Anaesthesiology ( ESA ) guidelines on the pre-operative evaluation of the adult undergoing noncardiac surgery is to present recommendations based on the available relevant clinical evidence . Well performed r and omised studies on the topic are limited and therefore many recommendations rely to a large extent on expert opinion and may need to be adapted specifically to the healthcare systems of individual countries . This article aims to provide an overview of current knowledge on the subject with an assessment of the quality of the evidence in order to allow anaesthesiologists all over Europe to integrate - wherever possible - this knowledge into daily patient care . The Guidelines Committee of the ESA formed a task force comprising members of the previous task force , members of ESA scientific subcommittees and an open call for volunteers was made to all individual active members of the ESA and national societies . Electronic data bases were search ed from July 2010 ( end of the literature search of the previous ESA guidelines on pre-operative evaluation ) to May 2016 without language restrictions . A total of 34 066 abtracts were screened from which 2536 were included for further analysis . Relevant systematic review s with meta-analyses , r and omised controlled trials , cohort studies , case-control studies and cross-sectional surveys were selected . The Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) system was used to assess the level of evidence and to grade recommendations . The final draft guideline was posted on the ESA website for 4 weeks and the link was sent to all ESA members , individual or national ( thus including most European national anaesthesia societies ) . Comments were collated and the guidelines amended as appropriate . When the final draft was complete , the Guidelines Committee and ESA Board ratified the guidelines INTRODUCTION The relationship between electrocardiograph ( ECG ) changes and troponin levels after the emergency orthopaedic surgery are not well characterised . The aim of this study was to determine the correlation between ECG changes ( ischaemia or arrhythmia ) , troponin elevations perioperatively and cardiac complications . MATERIAL S AND METHODS One hundred and eighty-seven orthopaedic patients over 60 years of age were prospect ively tested for troponin I and ECGs were performed on the fi rst 3 postoperative mornings or until discharge . RESULTS The incidences of pre- and postoperative troponin elevation were 15.5 % and 37.4 % respectively , the majority were asymptomatically detected . Most of the patients who sustained a troponin rise did not have any concomitant ECG changes ( 51/70 or 72.9 % ) . Postoperative ECG changes were noted in 18.4 % ( 34/185 ) and of those with ECG changes , slightly more than half ( 55.9 % ) had a troponin elevation . Most ECG changes occurred on postoperative day 1 and were non-ST elevation in type . ECG changes occurred more frequently with higher troponin levels . Postoperative troponin elevation ( P = 0.018 ) and not preoperative troponin level ( P = 0.060 ) was associated with ECG changes on univariate analysis . Two premorbid factors were predictors of postoperative ECG changes using multivariate logistical regression ; age [ odds ratio ( OR ) , 1.05 ; 95 % CI , 1.005 to 1.100 , P = 0.029 ) and sex OR , 2.4 ; 95 % CI , 1.069 to 5.446 , P = 0.034 ) . Twenty patients sustained postoperative cardiac complications ; 9 ( 45 % ) were associated with ECG changes and 16 ( 80 % ) with postoperative troponin elevation . Pre- or postoperative troponin elevation better predicted cardiac complications compared with preoperative ECG changes . CONCLUSION Electrocardiograph changes do not necessarily accompany troponin elevations after the emergency orthopaedic surgery but are more likely to have higher troponin levels . The best predictor of postoperative cardiac complications is troponin elevation AIMS We aim ed to evaluate the incremental value of high-sensitive troponin T ( hsTnT ) for risk prediction prior to non-cardiac surgery in comparison with the established revised cardiac index . METHODS AND RESULTS In this prospect i ve , international multicentre observational study , 979 patients prior to non-cardiac surgery were enrolled . The endpoints were in-hospital mortality , the combination of death , acute myocardial infa rct ion , cardiac arrest , cardio-pulmonary resuscitation , and acute decompensated heart failure . Twenty-five patients ( 2.6 % ) deceased and 36 ( 3.7 % ) of the patients experienced the combined endpoint . Cardiac markers were elevated in those patients who died when compared with survivors ( hsTnT : 21 ng/L vs. 7 ng/L ; P < 0.001 ; NT-proBNP : 576 pg/mL vs. 166 pg/mL ; P < 0.001 ) . Applying a cut-off for hsTnT of 14 ng/L and for NT-proBNP of 300 pg/mL , those patients with elevated hsTnT had a mortality of 6.9 vs. 1.2 % ( P < 0.001 ) and with elevated NT-proBNP 4.8 vs. 1.4 % ( P = 0.002 ) . The highest AUC of the ROC curve was found for hsTnT as a predictor for mortality of 0.809 . In a multivariate Cox regression analyses , hsTnT was the strongest independent predictor for the combined endpoint [ HR 2.6 ( 95 % CI : 1.3 - 5.3 ) ; P = 0.01 ] . CONCLUSION High-sensitive troponin T provides strong prognostic information in patients undergoing non-cardiac surgery incremental to the widely accepted revised cardiac Output:	Our study indicates that although preoperative cTn and perioperative change in cTn might be valuable predictors of MACE and /or all-cause mortality in adult noncardiac surgical patients , its overall prognostic performance remains uncertain .
MS2973	*TASK* the task is to summarize an input biomedical literature in six sentences *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 influence of an opinion leader intervention on adherence to Unstable Angina ( UA ) guidelines compared with a traditional quality improvement model was investigated . Research Design . A group-r and omized controlled trial with 2210 patients from 21 hospitals was design ed . There were three intervention arms : ( 1 ) no intervention ( NI ) ; ( 2 ) a traditional Health Care Quality Improvement Program ( HCQIP ) ; and ( 3 ) a physician opinion leader in addition to the HCQIP model ( OL ) . Quality indicators included : electrocardiogram within 20 minutes , antiplatelet therapy within 24 hours and at discharge , and heparin and & bgr;-blockers during hospitalization . Hospitals could determine the specific indicators they wished to target . Potential cases of UA were identified from Medicare cl aims data . UA confirmation was determined by a clinical algorithm based on data abstract ed from medical records . Data analyses included both hospital level analysis ( analysis of variance ) and patient level analysis ( generalized linear models ) . Results . The only statistically significant postintervention difference in percentage compliant was greater improvement for the OL group in the use of antiplatelet therapy at 24 hours in both hospital level ( P = 0.01 ) and patient level analyses ( P < 0.05 ) compared with the HCQIP and NI groups . When analyses were confined to hospitals that targeted specific indicators , compared with the HCQIP hospitals , the OL hospitals showed significantly greater change in percentage compliant postintervention in both antiplatelet therapy during the first 24 hours ( 20.2 % vs. −3.9 % , P = 0.02 ) and heparin ( 31.0 % vs.9.1 % , P = 0.05 ) . Conclusions . The influence of physician opinion leaders was unequivocally positive for only one of five quality indicators . To maximize adherence to best practice s through physician opinion leaders , more research on how these physicians influence health care delivery in their organizations will be required BACKGROUND Public agencies responsible for implementing health care policies often adapt and disseminate clinical practice guidelines , but the effectiveness of mass dissemination of guidelines is unknown . AIM To study the effects of guideline dissemination on physicians ' prescribing practice s for the treatment of stable angina pectoris . DESIGN R and omized controlled trial . METHODS A sample of 3293 Quebec physicians were r and omly assigned to receive a one-page summary of clinical practice guidelines on the treatment of stable angina ( in February 1999 ) , to receive the summary and a reminder ( in February and March 1999 , respectively ) , or to receive no intervention ( controls ) . The prescribing profiles of participants , as well as sociodemographic characteristics of the physicians and their patients , were examined for June-December 1999 . RESULTS The intervention had no effect on prescription rates of beta-blockers , antiplatelet agents , or hypolipaemic drugs . Compared to 1997 data for the same physicians , there was an overall 10 % increase in appropriate prescription rates , irrespective of the intervention . DISCUSSION In-house production and dissemination of clinical practice guidelines may not improve physicians ' practice patterns if there is pre-existing substantial scientific consensus on the issue Abstract Objective : To study the efficacy of case method learning , for general practitioners , on patients ' lipid concentrations in the secondary prevention of coronary artery disease . Design : Prospect i ve controlled trial . Setting : Södertälje , Stockholm County , Sweden . Participants : 255 consecutive patients with coronary artery disease . Intervention : Guidelines were mailed to all general practitioners ( n=54 ) and presented at a common lecture . General practitioners who were r and omised to the intervention group participated in recurrent case method learning dialogues at their primary healthcare centres during a two year period . A locally well known cardiologist served as a facilitator . Main outcome measure : Concentration of low density lipoprotein cholesterol at baseline and after two years . Analysis according to intention to treat ( intervention and control groups ( n=88 ) ) was based on group affiliation at baseline . Results : Low density lipoprotein cholesterol was reduced by 0.5 mmol/l ( 95 % confidence interval 0.2 to 0.8 mmol/l ) ( 9.3 % ( 2.9 % to 15.8 % ) ) from baseline in patients in the intervention group and by 0.5 ( 0.1 to 0.9 ) mmol/l compared with controls ( P<0.05 ) . No change occurred in the control group ( 0.0 ( −0.2 to 0.2 ) mmol/l ) . Low density lipoprotein cholesterol decreased by 0.6 ( 0.4 to 0.8 ) mmol/l in a group of patients who received specialist care . Conclusion : Case method learning result ed in a lowering of low density lipoprotein cholesterol in the primary care patients with coronary artery disease comparable to that achieved at a specialist clinic . Conventional presentation of practice guidelines had no effect PURPOSE To assess the effects of an intervention involving dissemination of treatment recommendations to primary care physicians treating out patients with acute myocardial infa rct ion or heart failure . METHODS The study comprised 509 patients with myocardial infa rct ion and 323 patients with heart failure who were discharged from hospital . The primary care physicians caring for these patients were assigned r and omly to either the intervention or control group ; the intervention group was mailed practice guidelines immediately after patient discharge , and patients were cited by name . During a 6-month assessment period , the records of primary care physicians ( and cardiologists , if any ) were review ed to assess mean conformance with the guidelines , using seven measures of care for myocardial infa rct ion and eight measures of care for heart failure . RESULTS After adjusting for demographic and clinical characteristics of patients , and the number of eligible measures per patient , we observed no effect of the intervention on care of patients with myocardial infa rct ion ( odds ratio [ OR ] = 0.98 ; 95 % confidence interval [ CI ] : 0.81 to 1.17 ) or heart failure ( OR = 1.25 ; 95 % CI : 0.96 to 1.59 ) . However , there was a higher likelihood of conformance with measures for patients with infa rct ion ( OR = 1.56 ; 95 % CI : 1.29 to 1.87 ) or heart failure ( OR = 1.71 ; 95 % CI : 1.29 to 2.23 ) who had also been seen by a cardiologist during the 6-month assessment period . CONCLUSION Mailing treatment recommendations did not improve the quality of care of recently discharged patients with myocardial infa rct ion or heart failure . However , efforts to include cardiologists in the care of these patients might be worthwhile Background — Hypertension control rates remain suboptimal . Pharmacists ’ scope of practice is evolving , and their position in the community may be ideal for improving hypertension care . We aim ed to study the impact of pharmacist prescribing on blood pressure ( BP ) control in community-dwelling patients . Methods and Results — We design ed a patient-level , r and omized , controlled trial , enrolling adults with above-target BP ( as defined by Canadian guidelines ) through community pharmacies , hospitals , or primary care teams in 23 communities in Alberta . Intervention group patients received an assessment of BP and cardiovascular risk , education on hypertension , prescribing of antihypertensive medications , laboratory monitoring , and monthly follow-up visits for 6 months ( all by their pharmacist ) . Control group patients received a wallet card for BP recording , written hypertension information , and usual care from their pharmacist and physician . Primary outcome was the change in systolic BP at 6 months . A total of 248 patients ( mean age , 64 years ; 49 % male ) were enrolled . Baseline mean±SD systolic/diastolic BP was 150±14/84±11 mm Hg . The intervention group had a mean±SE reduction in systolic BP at 6 months of 18.3±1.2 compared with 11.8±1.9 mm Hg in the control group , an adjusted difference of 6.6±1.9 mm Hg ( P=0.0006 ) . The adjusted odds of patients achieving BP targets was 2.32 ( 95 % confidence interval , 1.17–4.15 in favor of the intervention ) . Conclusions — Pharmacist prescribing for patients with hypertension result ed in a clinical ly important and statistically significant reduction in BP . Policy makers should consider an exp and ed role for pharmacists , including prescribing , to address the burden of hypertension . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00878566 Background : The 2007 American College of Cardiologists/American Heart Association Guidelines on Perioperative Cardiac Evaluation and Care for Noncardiac Surgery is the st and ard for perioperative cardiac evaluation . Recent work has shown that residents and anesthesiologists do not apply these guidelines when tested . This research hypothesized that a decision support tool would improve adherence to this consensus guideline . Methods : Anesthesiology residents at four training programs participated in an unblinded , prospect i ve , r and omized , cross-over trial in which they completed two tests covering clinical scenarios . One quiz was completed from memory and one with the aid of an electronic decision support tool . Performance was evaluated by overall score ( % correct ) , number of incorrect answers with possibly increased cost or risk of care , and the amount of time required to complete the quizzes both with and without the cognitive aid . The primary outcome was the proportion of correct responses attributable to the use of the decision support tool . Results : All anesthesiology residents at four institutions were recruited and 111 residents participated . Use of the decision support tool result ed in a 25 % improvement in adherence to guidelines compared with memory alone ( P < 0.0001 ) , and participants made 77 % fewer incorrect responses that would have result ed in increased costs . Use of the tool was associated with a 3.4-min increase in time to complete the test ( P < 0.001 ) . Conclusions : Use of an electronic decision support tool significantly improved adherence to the guidelines as compared with memory alone . The decision support tool also prevented inappropriate management steps possibly associated with increased healthcare costs BACKGROUND : Electronic information systems have been proposed as one means to reduce medical errors of commission ( doing the wrong thing ) and omission ( not providing indicated care ) . OBJECTIVE : To assess the effects of computer-based cardiac care suggestions . DESIGN : A r and omized , controlled trial targeting primary care physicians and pharmacists . SUBJECTS : A total of 706 out patients with heart failure and /or ischemic heart disease . INTERVENTIONS : Evidence -based cardiac care suggestions , approved by a panel of local cardiologists and general internists , were displayed to physicians and pharmacists as they cared for enrolled patients . MEASUREMENTS : Adherence with the care suggestions , generic and condition-specific quality of life , acute exacerbations of their cardiac disease , medication compliance , health care costs , satisfaction with care , and physicians ’ attitudes toward guidelines . RESULTS : Subjects were followed for 1 year during which they made 3,419 primary care visits and were eligible for 2,609 separate cardiac care suggestions . The intervention had no effect on physicians ’ adherence to the care suggestions ( 23 % for intervention patients vs 22 % for controls ) . There were no intervention-control differences in quality of life , medication compliance , health care utilization , costs , or satisfaction with care . Physicians viewed guidelines as providing helpful information but constraining their practice and not helpful in making decisions for individual patients . CONCLUSIONS : Care suggestions generated by a sophisticated electronic medical record system failed to improve adherence to accepted practice guidelines or outcomes for patients with heart disease . Future studies must weigh the benefits and costs of different ( and perhaps more Draconian ) methods of affecting clinician behavior AIM OF THE STUDY The European Resuscitation Council ( ERC ) guidelines changed in 2005 . We investigated the impact of these changes on no flow time and on the quality of cardiopulmonary resuscitation ( CPR ) . MATERIAL S AND METHODS Simulated cardiac arrest ( CA ) scenarios were managed r and omly in manikins using ERC 2000 or 2005 guidelines . Pairs of paramedics/paramedic students treated 34 scenarios with 10min of continuous ventricular fibrillation . The rhythm was analysed and defibrillation shocks were delivered with a semi-automatic defibrillator , and breathing was assisted with a bag-valve-mask ; no intravenous medication was given . Time factors related to human intervention and time factors related to device , rhythm analysis , charging and defibrillation were analysed for their contribution to no flow time ( time without chest compression ) . Chest compression quality was also analysed . RESULTS No flow time ( mean+/-S.D. ) was 66+/-3 % of CA time with ERC 2000 and 32+/-4 % with ERC 2005 guidelines ( P<0.001 ) . Human factor interventions occupied 114+/-4s ( ERC 2000 ) versus 107+/-4s ( ERC 2005 ) during 600-s scenarios ( P=0.237 ) . Device factor interventions took longer using ERC 2000 guidelines : 290+/-19s versus 92+/-15s ( P<0.001 ) . The total number of chest compressions Output:	Conclusions : This systematic review showed that CPGs could be useful to improve the process and structure of health care and , to a lesser extent , to improve the results in patients . There are probably still undiscovered variables that interfere with the use of the CPGs and , therefore , with their impact .
MS2974	*TASK* the task is to summarize an input biomedical literature in six sentences *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 are conducting a community-based cluster-r and omized trial in rural Alabama , testing a peer-support intervention design ed to improve diabetes self-care behaviors . We describe recruitment and data collection approaches used , focusing on strategies that created community partnerships and facilitated recruitment in underserved , rural , largely minority communities . Key recruitment and data collection strategies included early community engagement ; pilot testing of procedures ; inclusion of community members as study team members , recruiters , and data collectors ; data collection at community venues to minimize participant travel requirements ; and provision of a multi-disciplinary diabetes education program to both intervention and control participants . A total of 424 participants were recruited and enrolled ( 400 targeted ) . Of the 759 referrals received , 78.9 % ( n=599 ) successfully completed telephone screening . Of these , 78.8 % ( n=472 ) were eligible and scheduled for a local enrollment day , and 81.4 % ( n=384 ) attended and enrolled in the study . In addition , community members who walked in and expressed interest were screened , and 40 eligible and willing individuals were consented and enrolled . We exceeded recruitment goals in underserved , rural communities in Alabama . This success was due in large part to community partnerships that facilitated community involvement on several levels : engaging the community early in study proposal and design ; hiring community members to fill various capacities as research team members , recruiters , and data collectors ; conducting data collection within communities ; and collecting additional contact information to maintain communication . Providing diabetes education to all participants , including intervention and control , helped ensure that everyone stood to benefit and likely enhanced overall participation Purpose To describe methods used to recruit and retain low-income Latinos in a r and omized clinical trial ( RCT ) of a diabetes self-management intervention at 5 community health centers ( CHCs ) in Massachusetts . Methods Consent from primary care providers ( PCPs ) was obtained to screen their patients . Trained site research coordinators ( SRCs ) screened , recruited , and enrolled participants following a multistep process ( medical record review s , PCP approval , a patient eligibility interview ) and provided support for retention efforts . Assessment staff were trained in motivational strategies to facilitate retention and received ongoing support from a retention coordinator . Electronic tracking systems facilitated recruitment and retention activities . Results Of an initial pool of 1176 patients , 1034 were active at the time of screening , 592 ( 57 % ) were eligible by medical record review , and 487 received PCP approval ( 92 % of review ed patients ) . Of these , 293 patients completed the patient screening interview ( 60 % of patients with PCP approval , and 76 % of those reached ) , and 276 were eligible . Sixteen percent of all active patients refused participation , and 8 % of contacted patients were unreachable . Two hundred fifty-two patients were r and omized after completion of baseline assessment s. Clinical , behavioral , and psychosocial assessment completion rates were 92 % , 77 % , and 86 % at 12-month follow-up , respectively , and 93 % of patients completed at least one study assessment at 12 months . Conclusions CHCs are a prime setting for translation research aim ed to eliminate diabetes health disparities . Successful recruitment and retention efforts must address institutional/organizational , research team , and patient-related challenges . References 1 . US Department of Health and Human Services , Centers for Disease Control and Prevention . Age-adjusted prevalence of diagnosed diabetes by race/ethnicity and sex in the United States , 1980 - 2005 . Available at : www.cdc.gov/diabetes/statistics/prev/ national/figraceethsex.htm . Accessed January 21 , 2010 . 2 . US Census Bureau . Annual estimates of the population by sex , race , and Hispanic or Latino origin for the United States : April 1 , 2000 to July 1 , 2006 . Available at : www.census.gov/popest/ national/asrh/NC-EST2006-srh.html . Accessed January 21 , 2010 . 3 . National Center for Health Statistics . Early release of selected estimates based on data from the January-September 2006 National Health Interview Survey . Available at : http://www . cdc.gov/nchs/about/major/nhis/released200703.htm . Accessed January 12 , 2010 . 4 . Centers for Disease Control and Prevention . Self-reported prevalence of diabetes among Hispanics : United States , 1994 - 1997 . MMWR . 1999;48:8 - 12 . 5 . Harris MI , Klein R , Cowie CC , Rowl and M , Byrd-Holt DD . Is the risk of diabetic retinopathy greater in non-Hispanic blacks and Mexican Americans than in non-Hispanic whites with type 2 diabetes ? A U.S. population study . Diabetes Care . 1998 ; 21:1230 - 1235 . 6 . Franklin GM , Kahn LB , Baxter J , Marshall JA , Hamman RF . Sensory neuropathy in non-insulin-dependent diabetes mellitus : the San Luis Valley Diabetes Study . Am J Epidemiol . 1990;131:633 - 643 . 7 . Agency for Healthcare Research and Quality . National Healthcare Disparities Report , 2006 . Rockville , MD : Agency for Healthcare Research and Quality ; 2006 . Available at : http://www.ahrq.gov/ qual/nhdr06/nhdr06.htm . Accessed January 12 , 2010 . 8 . National Institute of Diabetes and Digestive and Kidney Diseases , National Diabetes Information Clearinghouse ( NDIC ) . National diabetes statistics . Available at : http://diabetes.niddk.nih.gov/dm/ pubs/statistics/index.htm . Accessed January 12 , 2010 . 9 . US Department of Health and Human Services , Office of Minority Research . Diabetes and Hispanic Americans . Available at : http://www.omhrc.gov/templates/content.aspx?lvl=2&lvllD= 54&ID=3324 . Accessed December 10 , 2009 . 10 . The Diabetes Control and Complications Trial Research Group . The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus . N Engl J Med . 1993;329 : 977 - 986 . 11 . UK Prospect i ve Diabetes Study ( UKPDS ) Group . Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes ( UKPDS 33 ) . Lancet . 1998;352:837 - 853 . 12 . Norris SL , Engelgau MM , Narayan KM . Effectiveness of self-management training in type 2 diabetes : a systematic review of r and omized controlled trials . Diabetes Care . 2001;24:561 - 587 . 13 . Brown SA , Garcia AA , Kouzekanani K , Hanis CL . Culturally competent diabetes self-management education for Mexican Americans : the Starr County border health initiative . Diabetes Care . 2002;25:259 - 268 . 14 . Lorig K , Ritter PL , Villa F , Piette JD . Spanish diabetes self-management with and without automated telephone reinforcement : two r and omized trials . Diabetes Care . 2008 ; 31:408 - 414 . 15 . Rosal MC , Olendzki B , Reed GW , Gumieniak O , Scavron J , Ockene IS . Diabetes self-management among low-income Spanish speaking patients : a pilot study . Ann Behav Med . 2005;29:225 - 235 . 16 . Mauldon M , Melkus GD , Cagganello M. Tom and o Control : a culturally appropriate diabetes education program for Spanish-speaking individuals with type 2 diabetes mellitus . Evaluation of a pilot project . Diabetes Educ . 2006;32:751 - 760 . 17 . Centers for Disease Control and Prevention , National Center for Health Statistics . Age-adjusted percentage of civilian , noninstitutionalized population with diagnosed diabetes , Hispanics , United States , 1980 - 2007 . Available at : http://www.ced.gov/diabetes/ statistics/prev/national/figbyhispanic.htm . Accessed March 31 , 2010 . 18 . Flegal KM , Ezzati TM , Harris MI . Prevalence of diabetes in Mexican Americans , Cubans , and Puerto Ricans from the Hispanic health and nutrition examination survey 1982 - 1984 . Diabetes Care . 1991;14(7 Suppl):528 - 538 . 19 . Lemon SC , Zapka JG , Estabrook B , Benjamin E. Challenges to research in urban community health centers . Am J Public Health . 2006;96:626 - 628 . 20 . H and ley MA , Hammer H , Schillinger D. Navigating the terrain between research and practice : a Collaborative Research Network ( CRN ) case study in diabetes research . J Am Board Fam Med . 2006;19:85 - 92 . 21 . Piatt GA , Orchard TJ , Emerson S. Translating the chronic care model into the community : results from a r and omized controlled trial of a multifaceted diabetes care intervention . Diabetes Care . 2006;29:811 - 817 . 22 . Frayne SM , Burns RB , Hardt EJ , Rosen AK , Moskowitz MA . The exclusion of non-English-speaking persons from research . J Gen Intern Med . 1996;11:39 - 43 . 23 . Durant RW , Davis RB , St George M , Williams IC , Blumenthal C , Corbie-Smith GM . Participation in research studies : factors associated with failing to meet minority recruitment goals . Ann Epidemiol . 2007;17:634 - 642 . 24 . Centers for Disease Control and Prevention , Department of Health and Human Services . Diabetes data and trends . Available at : http : www.cdc.gov/diabetes/statistics/prev/national/. Accessed March 31 , 2010 . 25 . Surani S , Aguillar R , Komari V , Surani A , Subramanian S. Influence of Hispanic ethnicity in prevalence of diabetes mellitus in sleep apnea and relationship to sleep phase . Postgrad Med . 2009;121:108 - 112 . 26 . Link CL , McKinlay JB . Disparities in the prevalence of diabetes : is it race/ethnicity or socioeconomic status ? Results from the Boston Area Community Health ( BACH ) survey . Ethn Dis . 2009;19:288 - 292 . 27 . Bryson CL , Ross HJ , Boyko EJ , Young BA . Racial and ethnic variations in albuminuria in the US Third National Health and Nutrition Examination Survey ( NHANES III ) population : associations with diabetes and level of CKD . Am J Kidney Dis . 2006 ; 48:720 - 726 . 28 . Gross R , Olfson M , Gameroff MJ . Depression and glycemic control in Hispanic primary care patients with diabetes . J Gen Intern Med . 2005;20:460 - 466 . 29 . Trief PM , Morin PC , Izquierdo R. Depression and glycemic control in elderly ethnically diverse patients with diabetes : the IDEATel project . Diabetes Care . 2006 ; 29:830 - 835 . 30 . McCarthy CR . Historical background of clinical trials involving women and minorities . Acad Med . 1994;69:695 - 698 . 31 . Rosal MC , Benjamin EM , Pekow PS , Lemon SC , von Goeler D. Opportunities and challenges for diabetes prevention at two community health centers . Diabetes Care . 2008 ; 31:247 - 254 . 32 . Blumenthal DS , Sung J , Coates R , Williams J , Liff J. Recruitment and retention of subjects for a longitudinal cancer prevention study in an inner-city black community . Health Serv Res . 1995;30(1 Pt 2):197 - 205 . 33 . UyBico SJ , Pavel S , Gross CP . Recruiting vulnerable population s into research : a systematic review of recruitment interventions . J Gen Intern Med . 2007;22:852 - 863 . 34 . Corbie-Smith GM . Minority recruitment and participation in health research . N C Med J. 2004 ; 65:385 - 387 . 35 . Bruner DW , Jones M , Buchanan D , Russo J. Reducing cancer disparities for minorities Output:	Multiple and flexible strategies targeting providers and participants at provider sites and within communities might be needed to enroll underrepresented population s into clinical trials
MS2975	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND This study tested the impact of free nicotine patches plus proactive telephone peer support to help low-income women stop smoking . METHODS A total of 214 Medicaid-eligible women smokers of childbearing age were r and omized to receive free nicotine patches through the mail or free nicotine patches through the mail plus the provision of proactive support by telephone from a woman ex-smoker for up to 3 months . Assessment s were conducted by telephone at baseline , 10 days , and 3 and 6 months after enrollment . RESULTS At the 3-month follow-up , significantly more women in the patch plus proactive telephone support condition were abstinent ( 42 % ) compared to the patch only condition ( 28 % ) ( P = 0.03 ) . Similarly , more women in the experimental condition were abstinent at both the 10-day and 3-month assessment s ( 32 v 19 % , P = 0.02 ) . However , differences were not found at the 6-month follow-up , suggesting that the addition of proactive telephone peer support enhanced short-term , but not long-term cessation . CONCLUSIONS This is the first study to demonstrate a beneficial effect for the addition of proactive telephone support as an adjunct to free nicotine replacement in a low-income population Smoking-cessation services are an unmet need among the homeless , who smoke at rates more than 4 times the national estimate . Successful interventions have high potential for improving tobacco-related health disparities among homeless smokers . Contingency management ( CM ) is a behavioral intervention with efficacy in a number of substance-use disorder population s , including smokers . However , no r and omized studies have evaluated the effect of CM in homeless smokers . We examined smoking-related outcomes in homeless smokers ( N = 70 ) r and omized to st and ard-care ( SC ) smoking cessation involving transdermal nicotine-replacement therapy ( NRT ) , st and ard counseling , and carbon monoxide ( CO ) monitoring or the same SC plus CM for negative CO sample su bmi ssions . Participants r and omized to CM achieved significantly longer duration s of consecutive abstinence and su bmi tted a significantly higher proportion of CO-negative sample s relative to st and ard-care participants . At 4 weeks postquit day , 22 % were abstinent in the CM condition and 9 % were abstinent in the SC condition . At the 6-month follow-up , about 10 % of smokers in both conditions were abstinent . This study demonstrates that CM is an efficacious option to increase initial quit rates in homeless smokers , but methods to extend effects are needed INTRODUCTION Evidence -based treatments for tobacco dependence are significantly less effective for smokers of lower socioeconomic status which contributes to socioeconomic disparities in smoking prevalence rates and health . We aim ed to reduce the socioeconomic gradient in treatment outcomes by systematic ally adapting evidence -based , cognitive-behavioral treatment for tobacco dependence for diverse lower socioeconomic smokers . METHODS Participants were r and omized to adapted or st and ard treatment , received six 1-h group treatment sessions , and were followed for six months . We examined the effectiveness of the adapted treatment to improve treatment outcomes for lower socioeconomic groups . RESULTS Participants ( n=227 ) were ethnically , racially , and socioeconomically diverse . The adapted treatment significantly reduced the days to relapse for the two lowest socioeconomic groups : SES1 : M=76.6 ( SD 72.9 ) vs. 38.3 ( SD 60.1 ) days to relapse ( RR=0.63 95 % CI , 0.45 , 0.88 , p=0.0013 ) ; SES2 : M=88.2 ( SD 67.3 ) vs. 40.1 ( SD 62.6 days to relapse ( RR=0.57 95 % CI , 0.18 , 0.70 , p=0.0024 ) . Interactions between socioeconomic status and condition were significant for initial abstinence ( OR=1.26 , 95 % CI 1.09 , 1.46 , p=0.002 ) , approached significance for 3-month abstinence ( OR=0.90 , 95 % CI 0.80 , 1.01 , p<0.071 ) , and were not significant for 6-month abstinence ( OR=0.99 95 % CI 0.88 , 1.10 , p=0.795 ) . No significant differences in long-term abstinence were observed . CONCLUSION Systematic adaption of evidence -based treatment for tobacco dependence can significantly improve initial and short-term treatment outcomes for diverse lower socioeconomic smokers and reduce inequities in days to relapse . Novel methods of providing targeted extended support are needed to improve long-term outcomes Background Lower rates of smoking cessation are a major reason for the higher prevalence of smoking among socioeconomically disadvantaged adults . Because barriers to quitting are both more numerous and severe , socioeconomically disadvantaged smokers may benefit from more intensive intervention . We sought to determine whether a smoking cessation intervention delivered by public housing residents trained as Tobacco Treatment Advocates ( TTAs ) could increase utilization of cessation re sources and increase abstinence . Methods We conducted a group-r and omized trial among Boston public housing residents who were interested in quitting smoking . Participants at control sites received st and ard cessation material s and a one-time visit from a TTA who provided basic counseling and information about cessation re sources . Participants at intervention sites were eligible for multiple visits by a TTA who employed motivational interviewing , cessation counseling , and navigation to encourage smokers to utilize cessation treatment ( Smokers ' Quitline and clinic-based programs ) . Utilization and 7-day and 30-day point prevalence abstinence were assessed at 12 months . Self-reported abstinence was biochemically verified . Results Intervention participants ( n = 121 ) were more likely than control participants ( n = 129 ) to both utilize treatment programs ( adjusted odds ratio [ aOR ] : 2.15 ; 95 % confidence interval [ CI ] : 0.93 - 4.91 ) and 7-day and 30-day point prevalence abstinence ( aOR : 2.60 ( 1.72 - 3.94 ) ; 2.98 ( 1.56 - 5.68 ) , respectively ) . Mediation analysis indicated that the higher level of utilization did not explain the intervention effect . Conclusions An intervention delivered by peer health advocates was able to increase utilization of treatment programs and smoking abstinence among public housing residents . Future studies of similar types of interventions should identify the key mechanisms responsible for success . Implication s In order to narrow the large and growing socioeconomic disparity in smoking rates , more effective cessation interventions are needed for low-income smokers . Individual culturally-relevant coaching provided in smokers ' residences may help overcome the heightened barriers to cessation experienced by this group of smokers . In this study among smokers residing in public housing , an intervention delivered by peer health advocates trained in motivational interviewing , basic smoking cessation skills , and client navigation significantly increased abstinence at 12 months . Future research should address whether these findings are replicable in other setting s both within and outside of public housing OBJECTIVE To evaluate the effectiveness of a community based participatory research ( CBPR ) developed , multi-level smoking cessation intervention among women in subsidized housing neighborhoods in the Southeastern US . METHODS A total of n=409 women in 14 subsidized housing neighborhoods in Georgia and South Carolina participated in this group r and omized controlled trial conducted from 2009 to 2013 . Intervention neighborhoods received a 24-week intervention with 1:1 community health worker contact , behavioral peer group sessions , and nicotine replacement . Control neighborhoods received written cessation material s at weeks 1 , 6 , 12 , 18 . R and om coefficient models were used to compare smoking abstinence outcomes at 6 and 12months . Significance was set a p<0.05 . RESULTS The majority of participants ( 91.2 % ) were retained during the 12-month intervention period . Smoking abstinence rates at 12months for intervention vs. control were 9 % vs. 4.3 % , p=0.05 . Additional analyses accounting for passive smoke exposure in these multi-unit housing setting s demonstrated 12month abstinence rates of 12 % vs. 5.3 % , p=0.016 . However , in the multivariate regression analyses , there was no significant effect of the intervention on the odds of being a non-smoker ( OR=0.44 , 95 % CI : 0.18 - 1.07 ) . Intervention participants who kept coach visits , attended group sessions , and used patches were more likely to remain abstinent . CONCLUSIONS This CBPR developed intervention showed potential to engage smokers and reduce smoking among women in these high-poverty neighborhoods . Effectiveness in promoting cessation in communities burdened with fiscal , environmental and social inequities remains a public health priority Objectives To assess the effects of a novel oral health promotion program ( Oral Health 4 Life ; OH4L ) delivered through state-funded tobacco quitlines . Methods Using a semipragmatic design to balance experimental control and generalizability , we r and omized US quitline callers ( n = 718 ) to st and ard care or st and ard care plus OH4L . We followed participants for 6 months to assess effects on professional dental care and smoking abstinence . We collected data between 2015 and 2017 . Results Participants were racially diverse ( 42 % non-White ) and socioeconomically disadvantaged . Most ( 71 % ) reported fair or poor oral health , and all were overdue for routine dental care . At 6 months , professional dental care and abstinence did not significantly differ between arms , but abstinence favored the experimental arm and was significantly higher among experimental participants at 2 months in a complete case sensitivity analysis . Conclusions OH4L was not effective for promoting dental care , but integrating oral health counseling with quitline counseling may offer some advantage for smoking cessation . Public Health Implication s We offer a model for conducting semipragmatic trials and partnering with tobacco quitlines to evaluate population -level public health interventions OBJECTIVES There remains a need to identify effective smoking cessation interventions in severely disadvantaged population s. This trial aim ed to examine the effectiveness of an intervention ( Call it Quits ) developed to promote smoking cessation and delivered by community social service case-workers . METHODS Call it Quits was a pragmatic , parallel r and omised trial of a case-worker delivered smoking cessation intervention conducted in a non-government community social service organisation in New South Wales ( NSW ) , Australia . Adult smokers requiring financial assistance were r and omly assigned to the five-session Call it Quits intervention or usual care control group . Of the 618 eligible individuals , 300 were r and omised to the intervention group , of whom 187 ( 62 % ) consented and 318 were r and omised to the control group , of whom 244 ( 77 % ) consented , result ing in 431 participants . The primary outcome measure was self-reported continuous abstinence up to 6-month follow-up with biochemical verification . Primary analysis was performed using all the available data from participants under the assumption the data is missing completely at r and om , followed by sensitivity analyses . RESULTS No statistically significant differences in the primary outcome were found ( 1.4 % in the control group versus 1.0 % in the intervention group , OR = 0.77 , p = 0.828 ) . CONCLUSIONS A multi-component smoking cessation intervention delivering motivational interviewing-based counselling and free NRT by a trained case-worker within a community social service setting was not effective at achieving abstinence in a highly disadvantaged sample of smokers but increased attempts to stop and led to a reduction in number of cigarettes smoked daily Background Tobacco use kills half a million people every month , most in low – middle income countries ( LMICs ) . There is an urgent need to identify potentially low-cost , scalable tobacco cessation interventions for these countries . Objective To evaluate a brief community outreach intervention delivered by health workers to promote tobacco cessation in India . Design Cluster-r and omised controlled trial . Setting 32 low-income administrative blocks in Delhi , half government authorised ( ‘ resettlement colony ’ ) and half unauthorised ( ‘ J.J. cluster ’ ) communities . Participants 1213 adult tobacco users . Interventions Administrative blocks were computer r and omised in a 1:1 ratio , to the intervention ( 16 clusters ; n=611 ) or control treatment ( 16 clusters ; n=602 ) , delivered and assessed at individual level between 07/2012 and 11/2013 . The intervention was single session quit advice ( 15 min ) plus a single training session in yogic breathing exercises ; the control condition comprised very brief quit advice ( 1 min ) alone . Both were delivered via outreach , with contact made though household visits . Measurements The primary outcome was 6-month sustained abstinence from all tobacco , assessed 7 months post intervention delivery , biochemically verified with salivary cotinine . Results The smoking cessation rate was higher in the intervention group Output:	INTERPRETATION We found evidence that individual-level interventions can assist disadvantaged smokers with quitting , but there were no large moderating effects of tailoring for disadvantaged smokers . Improvements in tailored intervention development might be necessary to achieve equity-positive smoking cessation outcomes .
MS2976	*TASK* the task is to summarize an input biomedical literature in six sentences *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 benefit of high-dose chemotherapy with autologous stem-cell transplantation ( ASCT ) as first-line treatment in patients with diffuse large B-cell lymphomas is still a matter of debate . To address this point , we design ed a r and omized phase III trial to compare rituximab plus cyclophosphamide , doxorubicin , vincristine , and prednisone (R-CHOP)-14 ( eight cycles ) with rituximab plus high-dose sequential chemotherapy ( R-HDS ) with ASCT . Patients and Methods From June 2005 to June 2011 , 246 high-risk patients with a high-intermediate ( 56 % ) or high ( 44 % ) International Prognostic Index score were r and omly assigned to the R-CHOP or R-HDS arm , and 235 were analyzed by intent to treat . The primary efficacy end point of the study was 3-year event-free survival , and results were analyzed on an intent-to-treat basis . Results Clinical response ( complete response , 78 % v 76 % ; partial response , 5 % v 9 % ) and failures ( no response , 15 % v 11 % ; and early treatment-related mortality , 2 % v 3 % ) were similar after R-CHOP versus R-HDS , respectively . After a median follow-up of 5 years , the 3-year event-free survival was 62 % versus 65 % ( P = .83 ) . At 3 years , compared with the R-CHOP arm , the R-HDS arm had better disease-free survival ( 79 % v 91 % , respectively ; P = .034 ) , but this subsequently vanished because of late-occurring treatment-related deaths . No difference was detected in terms of progression-free survival ( 65 % v 75 % , respectively ; P = .12 ) , or overall survival ( 74 % v 77 % , respectively ; P = .64 ) . Significantly higher hematologic toxicity ( P < .001 ) and more infectious complications ( P < .001 ) were observed in the R-HDS arm . Conclusion In this study , front-line intensive R-HDS chemotherapy with ASCT did not improve the outcome of high-risk patients with diffuse large B-cell lymphomas BACKGROUND High-dose therapy ( HDT ) followed by transplantation of autologous haemopoietic stem cells is frequently done as part of first-line therapy in young patients with high-risk aggressive B-cell lymphoma . We investigated whether HDT with cytotoxic agents identical to those used for conventional therapy followed by autologous stem-cell transplantation ( ASCT ) improved survival outcome compared with conventional chemotherapy when rituximab was added to both modalities . METHODS We did an open-label , r and omised trial comparing conventional chemotherapy ( cyclophosphamide , doxorubicin , vincristine , etoposide , prednisone ) and rituximab ( R-CHOEP-14 ) with dose-escalated sequential HDT and rituximab ( R-MegaCHOEP ) followed by repetitive ASCT in high-risk ( age-adjusted International Prognostic Index [ IPI ] 2 or 3 ) patients aged 18 - 60 years with aggressive B-cell lymphoma . Eligible patients received radiotherapy for bulky , extranodal disease , or both . R and omisation ( 1:1 ) used the Pocock minimisation algorithm ; patients were stratified by age-adjusted IPI factors , bulky disease , and centre . The primary endpoint was event-free survival . All analyses were done on the intention-to-treat population . This trial is registered with Clinical Trials.gov , number NCT00129090 . FINDINGS 136 patients were r and omly assigned to R-CHOEP-14 and 139 to R-MegaCHOEP . 130 patients in the R-CHOEP-14 group and 132 in the R-MegaCHOEP group were included in the intention-to-treat population . After a median of 42 months ( IQR 29 - 59 ) , 3-year event-free survival was 69·5 % ( 95 % CI 61·3 - 77·7 ) in the R-CHOEP-14 group and 61·4 % ( 52·8 - 70·0 ) in the R-MegaCHOEP group ( p=0·14 ; hazard ratio 1·3 , 95 % CI 0·9 - 2·0 ) . All 128 evaluable patients treated with R-MegaCHOEP had grade 4 leucopenia , as did 48 ( 58·5 % ) of 82 patients with documented blood counts in the R-CHOEP-14 group . All 128 evaluable patients in the R-MegaCHOEP group had grade 3 - 4 thrombocytopenia , as did 26 ( 33·8 % ) of 77 patients in the R-CHOEP-14 group with documented blood counts . The most important non-haematological grade 3 or 4 adverse event was infection , which occurred in 96 ( 75·0 % ) of 128 patients treated with R-MegaCHOEP and in 40 ( 31·3 % ) of 128 patients treated with R-CHOEP-14 . INTERPRETATION In young patients with high-risk aggressive B-cell lymphoma , R-MegaCHOEP was not superior to conventional R-CHOEP therapy and was associated with significantly more toxic effects . R-CHOEP-14 with or without radiotherapy remains a treatment option for these patients , with encouraging efficacy . FUNDING Deutsche Krebshilfe PURPOSE Salvage chemotherapy followed by high-dose therapy and autologous stem-cell transplantation ( ASCT ) is the st and ard treatment for relapsed diffuse large B-cell lymphoma ( DLBCL ) . Salvage regimens have never been compared ; their efficacy in the rituximab era is unknown . PATIENTS AND METHODS Patients with CD20(+ ) DLBCL in first relapse or who were refractory after first-line therapy were r and omly assigned to either rituximab , ifosfamide , etoposide , and carboplatin ( R-ICE ) or rituximab , dexamethasone , high-dose cytarabine , and cisplatin ( R-DHAP ) . Responding patients received high-dose chemotherapy and ASCT . RESULTS The median age of the 396 patients enrolled ( R-ICE , n = 202 ; R-DHAP , n = 194 ) was 55 years . Similar response rates were observed after three cycles of R-ICE ( 63.5 % ; 95 % CI , 56 % to 70 % ) and R-DHAP ( 62.8 % ; 95 CI , 55 % to 69 % ) . Factors affecting response rates ( P < .001 ) were refractory disease/relapse less than versus more than 12 months after diagnosis ( 46 % v 88 % , respectively ) , International Prognostic Index ( IPI ) of more than 1 versus 0 to 1 ( 52 % v 71 % , respectively ) , and prior rituximab treatment versus no prior rituximab ( 51 % v 83 % , respectively ) . There was no significant difference between R-ICE and R-DHAP for 3-year event-free survival ( EFS ) or overall survival . Three-year EFS was affected by prior rituximab treatment versus no rituximab ( 21 % v 47 % , respectively ) , relapse less than versus more than 12 months after diagnosis ( 20 % v 45 % , respectively ) , and IPI of 2 to 3 versus 0 to 1 ( 18 % v 40 % , respectively ) . In the Cox model , these parameters were significant ( P < .001 ) . CONCLUSION In patients who experience relapse more than 12 months after diagnosis , prior rituximab treatment does not affect EFS . Patients with early relapses after rituximab-containing first-line therapy have a poor prognosis , with no difference between the effects of R-ICE and R-DHAP 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 Lack of appropriate reporting of method ological details has previously been shown to distort risk of bias assessment s in r and omized controlled trials . The same might be true for observational studies . The goal of this study was to compare the Newcastle-Ottawa Scale ( NOS ) assessment for risk of bias between review ers and authors of cohort studies included in a published systematic review on risk factors for severe outcomes in patients infected with influenza . Methods Cohort studies included in the systematic review and published between 2008–2011 were included . The corresponding or first authors completed a survey covering all NOS items . Results were compared with the NOS assessment applied by review ers of the systematic review . Inter-rater reliability was calculated using kappa ( K ) statistics . Results Authors of 65/182 ( 36 % ) studies completed the survey . The overall NOS score was significantly higher ( p < 0.001 ) in the review ers ’ assessment ( median = 6 ; interquartile range [ IQR ] 6–6 ) compared with those by authors ( median = 5 , IQR 4–6 ) . Inter-rater reliability by item ranged from slight ( K = 0.15 , 95 % confidence interval [ CI ] = −0.19 , 0.48 ) to poor ( K = −0.06 , 95 % CI = −0.22 , 0.10 ) . Reliability for the overall score was poor ( K = −0.004 , 95 % CI = −0.11 , 0.11 ) . Conclusions Differences in assessment and low agreement between review ers and authors suggest the need to contact authors for information not published in studies when applying the NOS in systematic review BACKGROUND The efficacy of first-line intensive chemotherapy plus transplantation of autologous hematopoietic stem cells in adults with disseminated aggressive lymphoma is unknown . METHODS We compared high-dose therapy plus autologous stem-cell support with the st and ard regimen of cyclophosphamide , doxorubicin , vincristine , and prednisone ( CHOP ) in a r and omized trial . The patients were 15 to 60 years of age , had untreated aggressive lymphoma , and were at low , low intermediate , or high intermediate risk of death ( i.e. , a maximum of two adverse prognostic factors ) according to the age-adjusted International Prognostic Index . The primary outcome was event-free survival at five years . RESULTS Of 207 consecutive patients , 197 underwent r and omization ; 99 were assigned to receive CHOP , and 98 to receive high-dose chemotherapy plus stem-cell transplantation . Overall , 78 percent of the patients completed the assigned treatment ; the median follow-up was four years . The estimated event-free survival rate ( + /-SD ) at five years was significantly higher among patients who received high-dose therapy than among patients who received CHOP ( 55+/-5 percent vs. 37+/-5 percent , P=0.037 ) . Among patients with a high intermediate risk of death , according to the age-adjusted International Prognostic Index , the five-year survival rate was significantly higher after high-dose therapy than after CHOP ( 74+/-6 percent vs. 44+/-7 percent , P=0.001 ) . CONCLUSIONS High-dose chemotherapy with autologous stem-cell support is superior to CHOP in adults with disseminated aggressive lymphoma BACKGROUND The MInT study was the first to show improved 3-year outcomes with the addition of rituximab to a CHOP ( cyclophosphamide , doxorubicin , vincristine , and prednisone)-like regimen in young patients with good-prognosis diffuse large-B-cell lymphoma . Extended follow-up was needed to establish long-term effects . METHODS In the r and omised open-label MInT study , patients from 18 countries ( aged 18 - 60 years with none or one risk factor according to the age-adjusted International Prognostic Index [ IPI ] , stage II-IV disease or stage I disease with bulk ) were r and omly assigned to receive six cycles of a CHOP-like chemotherapy with or without rituximab . Bulky and extranodal sites received additional radiotherapy . R and omisation was done central ly with a computer-based tool and was stratified by centre , bulky disease , age-adjusted IPI , and chemotherapy regimen by use of a modified minimisation algorithm that incorporated a stochastic component . Patients and investigators were not masked to treatment allocation . The primary endpoint was event-free survival . Analyses were by intention to treat . This observational study is a follow-up of the MInT trial , which was stopped in 2003 , and is registered at Clinical Trials.gov , number NCT00400907 . FINDINGS The intention-to-treat population included 410 patients assigned to chemotherapy alone and 413 assigned to chemotherapy plus rituximab . After a median follow-up of 72 months ( range 0·03 - 119 ) , 6-year event-free survival was 55·8 % ( 95 % CI 50·4 - Output:	High-intermediate or high-risk untreated patients with DLBCL only achieved short-term survival benefit with the upfront ASCT
MS2977	*TASK* the task is to summarize an input biomedical literature in six sentences *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 compare intraoperative blood loss , perioperative hematocrit , and transfusion requirements in patients undergoing radical retropubic prostatectomy ( RRP ) versus robotic-assisted laparoscopic prostatectomy ( RALP ) by a single surgeon . METHODS During a 14-month period , 279 patients with localized carcinoma of the prostate were prospect ively enrolled in this comparative study . The decision of which surgical approach to use was by patient choice . Of the 279 patients , 176 underwent RALP and 103 underwent RRP . The serum hematocrit was obtained preoperatively and 24 hours postoperatively in all patients . The intraoperative blood loss was recorded , and transfusion requirements were noted . RESULTS Patients in the RALP group had significantly less intraoperative blood loss compared with the RRP group ( mean 191 mL versus 664 mL , P < 0.001 ) . Additionally , the difference in the discharge hematocrit ( 36.8 % versus 32.8 % , P < 0.001 ) and the mean perioperative change in hematocrit ( 8.0 % decrease versus 10.7 % decrease , P < 0.001 ) were significant between the RALP and RRP groups , respectively . Three patients in the RRP group ( 2.9 % ) and one in the RALP group ( 0.5 % ) required transfusion of blood products ( P = 0.14 ) . CONCLUSIONS The results of this study have shown that RALP is associated with less intraoperative bleeding than RRP , and patients undergoing RALP have a greater serum hematocrit at hospital discharge . The lack of a statistically significant difference in blood transfusion was partially attributable to the low transfusion rate in both groups in this series Computer-assisted telesurgical devices have recently been approved in the United States for general surgery . To determine the safety and efficacy of these procedures , we performed a prospect i ve trial of computer-enhanced “ robotic ” fundoplication compared to st and ard laparoscopic control procedures . Consecutive patients undergoing surgical treatment for gastroesophageal reflux were included . The operating surgeon worked at a console using a three-dimensional image and manipulated h and controls . Operative times , complications , and length of hospital stay were recorded . A st and ardized question naire was administered to evaluate symptoms . Twenty patients were entered into each group . There were no differences in age , preoperative weight , or sex . Operative times were significantly longer in the robot group ( 97 vs. 141 minutes ) . There were no complications and most patients went home the first postoperative day . At follow-up , symptoms were similar in both groups ; however , there was a significant difference in the number of patients taking antisecretory medication — none in the robotic group but six in the laparoscopic group reported regular use . Computer-assisted laparoscopic antireflux surgery is safe . However , operative times are longer , with little difference in outcomes . At the current level of technology and experience , robotic antireflux surgery appears to offer little advantage over st and ard laparoscopic approaches The background of this study is to compare prospect ively the oncological and functional results of open radical prostatectomy ( OP ) and robotic prostatectomy ( RP ) from the experience of a single surgeon . Between June 2002 and June 2007 , 422 patients underwent radical prostatectomy ( OP 199 , RP 223 ) . We divided OP patients into 89 early cases ( OP-I ) and 110 late cases ( OP-II ) before and after introduction of a robotic system , and RP patients into 35 early cases ( RP-I ) and 188 late cases ( RP-II ) . Functional outcomes were measured by use of vali date d question naires completed by the patients . There were no significant differences in preoperative characteristics among the four groups , except that RP-I patients had lower biopsy Gleason scores . In the RP groups the mean estimated blood loss was lower and mean duration s of hospital stay and bladder catheterization were shorter compared to those of the OP groups . The frequency of intraoperative complications was significantly lower in the RP-II group . The positive surgical margin rates in the RP-II group were similar to or lower than those in the OP groups when stratified by pathologic stage T2 and T3 . From one month after surgery , RP-II patients had higher continence rates than OP-II patients . For patients ≥60 years old , recovery of potency was better in the RP-II group . To conclude , RP by an experienced surgeon may have a similar or lower positive surgical margin rate than OP . Additionally , RP may lead to a shorter duration of bladder catheterization and hospital stay and better recovery of continence and potency than obtainable by OP Background — The incidence of silent cerebral lesions ( SCL ) after atrial fibrillation ( AF ) ablation is highly variable , depending on the technology used . Recently , an increased risk for SCL has been described for a novel , nonirrigated ablation tool using multielectrode phased radiofrequency ( PVAC ) . The aim of this prospect i ve study was to evaluate the incidence and long-term follow-up of SCL in patients undergoing robotically assisted pulmonary vein isolation ( RA-PVI ) as compared with manual PVI . Methods and Results — Circumferential PVI using irrigated radiofrequency current was performed on 70 patients ( 41 patients with paroxysmal AF , 59 % ) . Fifty patients underwent RA-PVI and 20 patients underwent a manual approach . Cerebral MRI was performed the day before and the day after the ablation procedure ; follow-up MRI was performed on 9 of 12 ( 75 % ) patients after a follow-up period of 21 months . SCLs were found in 12 of 70 ( 17 % ) patients in this study ; the incidence of SCLs was similar in patients undergoing RA-PVI as compared with manually ablated patients ( n=9 , 18 % versus n=3 , 15 % ; probability value=1.0 ) . In 1 patient undergoing manual PVI ( 1 % ) , an SCL with asymptomatic subarachnoid hemorrhage was detected ; the bleeding completely resolved within 1 month . Transient ischemic attack occurred in 1 ( 1 % ) patient 2 days after manual PVI . After a median follow-up period of 21 months , no residual SCLs were detected . Conclusions — The incidence of SCL using the robotic navigation system was 18 % in this study . Incidence and size of SCL appears to be similar after RA-PVI as compared with manual PVI . Repeat MRI showed no residual SCLs at long-term follow-up INTRODUCTION Lack of r and omized controlled trials ( RCTs ) that compare pure laparoscopic radical prostatectomy ( LRP ) with robot-assisted laparoscopic radical prostatectomy ( RALRP ) is an important gap of the literature related to the surgical treatment of the clinical ly localized prostate cancer ( PCa ) . AIM To provide the first prospect i ve r and omized comparison on the functional and oncological outcomes of LRP and RALRP for the treatment of the clinical ly localized PCa . METHODS Between 2007 and 2008 , 128 consecutive male patients were r and omized in two groups and treated by a single experienced surgeon with traditional LRP ( Group I-64 patients ) or RALRP ( Group II-64 patients ) in all cases with intent of bilateral intrafascial nerve sparing . MAIN OUTCOME MEASURES Primary end point was to compare the 12 months erectile function ( EF ) outcomes . Complication rates , continence outcomes , and oncological results were also compared . The sample size of our study was able , with an adequate power ( 1-beta > 0.90 ) , to recognize as significant large differences ( above 0.30 ) between incidence proportions of considered outcomes . RESULTS No statistically significant differences were observed for operating time , estimated blood loss , transfusion rate , complications , rates of positive surgical margins , rates of biochemical recurrence , continence , and time to continence . However , the 12-month evaluation of capability for intercourse ( with or without phosphodiesterase type 5 inhibitors ) showed a clear and significant advantage of RALRP ( 32 % vs. 77 % , P < 0.0001 ) . Time to capability for intercourse was significantly shorter for RALRP . Rates of return to baseline International Index of Erectile Function ( IIEF-6 ) EF domain score question naires ( questions 1 - 5 and 15 ) ( 25 % vs. 58 % ) and to IIEF-6 > 17 ( 38 % vs. 63 % ) were also significantly higher for RALRP ( P = 0.0002 and P = 0.008 , respectively ) . CONCLUSIONS Our study offers the first high-level evidence that RALRP provides significantly better EF recovery than LRP without hindering the oncologic radicality of the procedure . Larger RCTs are needed to confirm if a new gold-st and ard treatment in the field of RP has risen Background and aims Laparoscopic surgery has become the treatment of choice for cholecystectomy . Many studies showed that while this approach benefits the patient , the surgeon faces such distinct disadvantages as a poor ergonomic situation and limited degrees of freedom with limited motion as a consequence . Robots have the potential to overcome these problems . To evaluate the efficiency and feasibility of robotically assisted surgery ( RAC ) , we design ed a prospect i ve study to compare it with st and ard laparoscopic cholecystectomy ( SLC ) . Material s and methods Between 2001 and 2003 , 26 patients underwent SLC and 20 patients underwent RAC using the ZEUS system . The feasibility , safety , and possible advantages were evaluated . To assess the efficacy , the total time in the operating room was divided into preoperative , operative , and postoperative time frames . Results For RAC in comparison with SLC , the preoperative phase including equipment setup was significantly longer . In the intraoperative phase , the cut-closure time and camera and trocar insertion times were significantly longer . It is interesting to note that the net dissection time for the cystic artery , duct , and the gall bladder was not different from SLC . Conclusions The study demonstrates the feasibility of robotically assisted cholecystectomy without system-specific morbidity . There is time loss in several phases of robotic surgery due to equipment setup and deinstallation and therefore , presents no benefit in using the robot in laparoscopic cholecystectomy PURPOSE Robotic assisted laparoscopic radical cystectomy for bladder cancer has been reported with potential for improvement in perioperative morbidity compared to the open approach . However , most studies are retrospective with significant selection bias . MATERIAL S AND METHODS A pilot prospect i ve r and omized trial evaluating perioperative outcomes and oncologic efficacy of open vs robotic assisted laparoscopic radical cystectomy for consecutive patients was performed from July 2009 to June 2011 . RESULTS To date 47 patients have been r and omized with data available on 40 patients for analysis . Each group was similar with regard to age , gender , race , body mass index and comorbidities , as well as previous surgeries , operative time , postoperative complications and final pathological stage . We observed no significant differences between oncologic outcomes of positive margins ( 5 % each , p = 0.50 ) or number of lymph nodes removed for open radical cystectomy ( 23 , IQR 15 - 28 ) vs robotic assisted laparoscopic radical cystectomy ( 11 , IQR 8.75 - 21.5 ) groups ( p = 0.135 ) . The robotic assisted laparoscopic radical cystectomy group ( 400 ml , IQR 300 - 762.5 ) was noted to have decreased estimated blood loss compared to the open radical cystectomy group ( 800 ml , IQR 400 - 1,100 ) and trended toward a decreased rate of excessive length of stay ( greater than 5 days ) ( 65 % vs 90 % , p = 0.11 ) compared to the open radical cystectomy group . The robotic group also trended toward fewer transfusions ( 40 % vs 50 % , p = 0.26 ) . CONCLUSIONS Our study vali date s the concept of r and omizing patients with bladder cancer undergoing radical cystectomy to an open or robotic approach . Our results suggest no significant differences in surrogates of oncologic efficacy . Robotic assisted laparoscopic radical cystectomy demonstrates potential benefits of decreased estimated blood loss and decreased hospital stay compared to open radical cystectomy . Our results need to be vali date d in a larger multicenter prospect i ve r and omized clinical trial Current options for minimally invasive surgical treatment of single-vessel coronary artery disease include beating heart procedures without cardiopulmonary bypass ( CPB ) via mini-thoracotomy ( MIDCAB ) and totally endoscopic robot-assisted techniques ( TECAB ) with CPB . Both procedures are associated with potential myocardial stress before revascularization , such as single-lung ventilation ( SLV ) , temporary coronary artery occlusion , cardiac luxation , intrathoracic carbon dioxide insufflation , and extended CPB and operating time . In this echocardiographic study we sought to evaluate the extent of intraoperative segmental wall motion abnormalities ( SWMA ) during MIDCAB and TECAB surgery and to identify factors affecting SWMA . Forty-six patients with single-vessel coronary artery disease were studied . Sixteen patients were operated using the MIDCAB technique and 30 patients with TECAB . In both groups sequential trans Output:	The benefits of robotic surgery lacked robustness on RCT -sensitivity analyses . Conclusions Our results showed that robotic surgery contributed positively to some perioperative outcomes but longer operative times remained a shortcoming .
MS2978	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objective : The aim of this study was to evaluate display formats for an automated combat identification ( CID ) aid . Background : Verbally informing users of automation reliability improves reliance on automated CID systems . A display can provide reliability information in real time . Method : We developed and tested four visual displays that showed both target identity and system reliability information . Display type ( pie , r and om mesh ) and display proximity ( integrated , separated ) of identity and reliability information were manipulated . In Experiment 1 , participants used the displays while engaging targets in a simulated combat environment . In Experiment 2 , participants briefly viewed still scenes from the simulation . Results : Participants relied on the automation more appropriately with the integrated display than with the separated display . Participants using the r and om mesh display showed greater sensitivity than those using a pie chart . However , in Experiment 2 , the sensitivity effects were limited to lower reliability levels . Conclusion : The integrated display format and the r and om mesh display were the most effective displays tested . Application : We recommend the use of the integrated format and a r and om mesh display to indicate identity and reliability information with an automated CID system Objective : This study examined whether benefits of conflict probe automation would occur in a future air traffic scenario in which air traffic service providers ( ATSPs ) are not directly responsible for freely maneuvering aircraft but are controlling other nonequipped aircraft ( mixed-equipage environment ) . The objective was to examine how the type of automation imperfection ( miss vs. false alarm ) affects ATSP performance and attention allocation . Background : Research has shown that the type of automation imperfection leads to differential human performance costs . Method : Participating in four 30-min scenarios were 12 full-performance-level ATSPs . Dependent variables included conflict detection and resolution performance , eye movements , and subjective ratings of trust and self confidence . Results : ATSPs detected conflicts faster and more accurately with reliable automation , as compared with manual performance . When the conflict probe automation was unreliable , conflict detection performance declined with both miss ( 25 % conflicts detected ) and false alarm automation ( 50 % conflicts detected ) . Conclusion : When the primary task of conflict detection was automated , even highly reliable yet imperfect automation ( miss or false alarm ) result ed in serious negative effects on operator performance . Application : The further in advance that conflict probe automation predicts a conflict , the greater the uncertainty of prediction ; thus , design ers should provide users with feedback on the state of the automation or other tools that allow for inspection and analysis of the data underlying the conflict probe algorithm Output:	Our three-layered trust model provides a new lens for conceptualizing the variability of trust in automation .
MS2979	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: In this paper preliminary results are presented of a prospect i ve study design ed to examine the effect of maxillary fixation methods on postoperative stability . The purpose of this study was to evaluate the stability of Le Fort I osteotomy stabilized with semirigid fixation of the maxilla ( SRMF ) or rigid fixation of the maxilla ( RMF ) . All patients had skeletal Class III malocclusion and underwent bimaxillary surgery ( Le Fort I maxillary advancement with or without superior repositioning and bilateral sagittal split osteotomies of the m and ible ) . St and ardized cephalometric analysis was performed on serial radiographs of 42 patients immediately before surgery , 1 week after surgery , after release of fixation , and 1 year postoperatively . The patients were r and omized into 2 treatment groups : 23 patients received RMF ( group A ) , and 19 patients received SRMF ( group B ) . Within the groups , patients showed good stability with regard to their baseline characteristics . To show the therapeutic equivalence of the 2 treatments , analysis of the recorded data followed the approach for an equivalence trial . The mean surgical advancement was 5.34 + /- 1.50 mm for group A and 4.51 + /- 1.37 mm for group B. The mean amount of postsurgical relapse was 0.98 + /- 1.27 mm for group A and 0.30 + /- 1.04 mm for group B. Group A patients experienced 93 % of their relapse ( 0.92 mm ) during fixation , while group B patients experienced 96 % of their relapse ( 0.29 mm ) after release of fixation . RMF provided better stability than SRMF for all maxillary l and marks in the vertical plane . All considered points both in horizontal and vertical plane exhibited full equivalence for 95 % confidence intervals , which seems to indicate equivalent stability between the surgical procedures The aim of this study was to select a model of cephalometric variables to predict the results of early treatment of Class III malocclusion with rapid maxillary expansion and facemask therapy followed by comprehensive treatment with fixed appliances . Lateral cephalograms of 42 patients ( 20 boys , 22 girls ) with Class III malocclusion were analyzed at the start of treatment ( mean age 8 years 6 months + /- 2 years , at stage I in cervical vertebral maturation ) . All patients were reevaluated after a mean period of 6 years 6 months ( at stage IV or V in cervical vertebral maturation ) that included active treatment plus retention . At this time , the sample was divided into 2 groups according to occlusal criteria : a successful group ( 30 patients ) and an unsuccessful group ( 12 patients ) . Discriminant analysis was applied to select pretreatment predictive variables of long-term treatment outcome . Stepwise variable selection of the cephalometric measurements at the first observation identified 3 predictive variables . Orthopedic treatment of Class III malocclusion might be unfavorable over the long term when a patient 's pretreatment cephalometric records exhibit a long m and ibular ramus ( ie , increased posterior facial height ) , an acute cranial base angle , and a steep m and ibular plane angle . On the basis of the equation generated by the multivariate statistical method , the outcome of interceptive orthopedic treatment for each new patient with Class III malocclusion can be predicted with a probability error of 16.7 % The purpose of this study was to evaluate long-term dentofacial stability after bimaxillary surgery in skeletal Class III open bite patients . Twenty-three Japanese adults ( 5 males , 18 females ) were r and omly selected as the experimental group from the files of Tohoku University Dental Hospital according to the following criteria : ( 1 ) skeletal Class III malocclusion with anterior open bite , ( 2 ) simultaneous Le Fort I and sagittal split ramus osteotomies , and ( 3 ) complete set of cephalograms taken at predetermined intervals until 5 years after debonding . Based on the manner of maxillary surgical repositioning , they were divided into the following 2 groups : ( 1 ) impaction group of 13 subjects ( 2 males , 11 females ) who had maxillary superior repositioning without rotation of the palatal plane , and ( 2 ) rotation group of 10 subjects ( 3 males , 7 females ) who had maxillary repositioning with clockwise rotation of the palatal plane . These patients were compared to a control group of 11 adults ( 1 male , 10 females ) with skeletal Class III malocclusion without open bite who underwent bimaxillary surgery by the same techniques . Our data showed that overbite stability in the rotation group was better than that in the impaction group . This suggests that clockwise rotation of the palatal plane , which moves the anterior maxillary structures down , is an effective way to produce a reasonably stable correction of the anterior open bite . In contrast , superior repositioning of the maxilla that significantly rotates the m and ible in the closing direction should be applied with caution PURPOSE The aim of this study was to evaluate skeletal stability after double-jaw surgery for correction of skeletal Class III malocclusion to assess whether there were any differences between wire and rigid fixation of the m and ible . PATIENTS AND METHODS Thirty-seven Class III patients had Le Fort I osteotomy stabilized with plate and screws for maxillary advancement . Bilateral sagittal split osteotomy for m and ibular setback was stabilized with wire osteo synthesis and maxillom and ibular fixation for 6 weeks in 20 patients ( group 1 ) and with rigid internal fixation in 17 patients ( group 2 ) . Lateral cephalograms were taken before surgery , immediately after surgery , 8 weeks after surgery , and 1 year after surgery . RESULTS Before surgery , both groups were balanced with respect to linear and angular measurements of craniofacial morphology . One year after surgery , maxillary sagittal stability was excellent in both groups , and bilateral sagittal split osteotomy accounted for most of the total horizontal relapse observed . In group 1 , significant correlations were found between maxillary advancement and relapse at the posterior maxilla and between m and ibular setback and postoperative counterclockwise rotation of the ramus and m and ibular relapse . In group 2 , significant correlations were found between m and ibular setback and intraoperative clockwise rotation of the ramus and between m and ibular setback and postoperative counterclockwise rotation of the ramus and m and ibular relapse . No significant differences in postoperative skeletal and dental stability between groups were observed except for maxillary posterior vertical position . CONCLUSIONS Surgical correction of Class III malocclusion after combined maxillary and m and ibular procedures appears to be a fairly stable procedure independent of the type of fixation used to stabilize the m and ible PURPOSE The aim of this report was to compare the clinical and radiographic findings observed at the 12-month follow-up in 2 groups of 15 patients who underwent Le Fort I and bilateral sagittal split osteotomy for the correction of dental-skeletal Class III . In the first group , the condylar positioning devices were used , whereas in the second group , an alternative method was used for the intraoperative assessment of m and ibular repositioning . MATERIAL S AND METHODS All of the patients of our study in the immediate presurgical period were without temporom and ibular joint disorders and with a normal anatomic relationship between condyle and fossae . The condyle position and morphology were examined at the 12-month follow-up through cephalometric measurements and the postsurgical findings in both groups were compared with those observed in the presurgical period . RESULTS In all of the 30 patients in our study , no relapse or postsurgical temporom and ibular joint disturbance was observed at the 12-month follow-up . Variations in condyle position of more than 2 mm or 2 degrees were not observed in the 15 patients treated with condylar positioning devices . Changes in condyle position between 2 and 4 mm and 2 degrees and 4 degrees were observed in 6 of the 15 patients treated without the devices . CONCLUSIONS The use of condylar positioning devices can be avoided in patients with dental-skeletal Class III without presurgical temporom and ibular dysfunction . The manual positioning of the m and ibular condyle is easier , but it requires the utmost care and an experienced operator The criteria and scoring method for a system to evaluate the quality of r and omized control trials ( RCTs ) in dental research based on published reports is presented . This sytem is based on one devised for evaluation of RCTs in medicine . Items assessed in this system include r and omization and blinding procedures , subject selection criteria , treatment protocol s , and statistical analyses . Assessing the quality of RCTs can contribute to improved study design , implementation and reporting by investigators , and evaluation of reports by referees and editors of scientific journals Output:	Surgical correction of skeletal Class III malocclusion after combined maxillary and m and ibular procedures appears to be stable for maxillary advancements up to 5 mm and for the correction of presurgical sagittal intermaxillary discrepancies smaller than 7 mm
MS2980	*TASK* the task is to summarize an input biomedical literature in six sentences *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 prevent medication errors in prescribing , one needs to know their types and relative occurrence . Such errors are a great cause of concern as they have the potential to cause patient harm . The aim of this study was to determine the nature and types of medication prescribing errors in an Indian setting . Methods The medication errors were analyzed in a prospect i ve observational study conducted in 3 medical wards of a public teaching hospital in India . The medication errors were analyzed by means of Micromedex Drug-Reax data base . Results Out of 312 patients , only 304 were included in the study . Of the 304 cases , 103 ( 34 % ) cases had at least one error . The total number of errors found was 157 . The drug-drug interactions were the most frequently ( 68.2 % ) occurring type of error , which was followed by incorrect dosing interval ( 12 % ) and dosing errors ( 9.5 % ) . The medication classes involved most were antimicrobial agents ( 29.4 % ) , cardiovascular agents ( 15.4 % ) , GI agents ( 8.6 % ) and CNS agents ( 8.2 % ) . The moderate errors contributed maximum ( 61.8 % ) to the total errors when compared to the major ( 25.5 % ) and minor ( 12.7 % ) errors . The results showed that the number of errors increases with age and number of medicines prescribed . Conclusion The results point to the establishment of medication error reporting at each hospital and to share the data with other hospitals . The role of clinical pharmacist in this situation appears to be a strong intervention ; and the clinical pharmacist , initially , could confine to identification of the medication errors Objective To evaluate a matrix for determining the predominant type , cause category , and rate of medication prescribing errors , and to explore the effectiveness of hospital-based improvement initiatives among pediatric intensive care units ( PICUs ) . Design This study involved the prospect i ve identification of medication errors for categorization and evaluation by using a matrix methodology . A pretest-posttest design without a control group was used to explore the impact of initiatives employed to reduce medication error rates and severity . Setting PICUs in nine freest and ing , collaborating tertiary care children ’s hospitals that participated in both baseline and postintervention analyses . Methods We evaluated 12,026 PICU medication orders at baseline and 9,187 orders postintervention for prescribing errors , excluding resuscitation orders . A st and ardized tool and process captured error type , cause category , and severity for 2 wks before and after intervention . Three levels of error detection were used and included pharmacy order entry , PICU nurse order transcription , and team-based overview . Site-specific interventions were implemented , which included predominantly provider education as well as informational ( 47 % ) and dosing “ assists ” via preprinted orders , forcing functions , or prompts ( 39 % ) . Results Of baseline orders , 11.1 % had at least one prescribing error . The interception of prescribing errors improved 30.9 % ( 1.6 % of all orders at baseline , 2.0 % post intervention ) . Preventable adverse drug events were uncommon ( 0.6 % of all medication errors ) and of low severity at baseline ; most were wrong dose errors . The implementation of improvement initiatives , specific for each facility , result ed in a 31.6 % reduction in prescribing errors from 11.1 % to 7.6 % . However , site results varied considerably . Conclusions A benchmark for medication prescribing errors in the PICU was identified among nine children ’s hospitals . The methodology was successful in accounting for site-specific differences with regard to identifying and documenting errors as well as reporting results of improvement initiatives . Furthermore , the methodology employed was generalizable in the identification of predominant prescribing error types , which helped to track individual hospital improvement initiative development and implementation . Overall improvement in prescribing error rates was noted ; however , considerable variation in the success of improvement initiatives was noted and bears further attention Background : Medication errors at the time of hospital admission and discharge are common and can lead to preventable adverse drug events . The objective of this study was to describe the potential impact of a medication reconciliation process to identify and rectify medication errors at the time of hospital admission and discharge . Methods : Sixty r and omly selected patients were prospect ively enrolled at the time of admission to a Canadian community hospital . At admission , patients ’ medication orders were compared with pre-admission medication use based on medication vials and interviews with patients , caregivers , and /or outpatient healthcare providers . At discharge , pre-admission and in-patient medications were compared with discharge orders and written instructions . All variances were discussed with the prescribing physician and classified as intended or unintended ; unintended variances were considered to be medication errors . An internist classified the clinical importance of each unintended variance . Results : Overall , 60 % ( 95 % CI 48 to 72 ) of patients had at least one unintended variance and 18 % ( 95 % CI 9 to 28 ) had at least one clinical ly important unintended variance . None of the variances had been detected by usual clinical practice before reconciliation was conducted . Of the 20 clinical ly important variances , 75 % ( 95 % CI 56 to 94 ) were intercepted by medication reconciliation before patients were harmed . Discussion : Unintended medication variances at the time of hospital admission and discharge are common and clinical ly important . The medication reconciliation process identified and addressed most of these unintended variances before harm occurred . In this small study , medication reconciliation was a useful method for identifying and rectifying medication errors at times of transition . Reconciliation warrants broader evaluation Abstract Background : Medication safety research and clinical pharmacy practice today is primarily focused on managing preventable adverse drug events ( pADEs ) . Determinants of both pADEs and non-preventable adverse drug reactions ( ADRs ) have been identified . However , relatively little is known on the overlap between these determinants and the balance of preventable and non-preventable harm in patients experience in modern computerized hospitals . Objective : The aim of this study was to analyse the prevalence of pADEs and non-preventable ADRs as well as the determinants , including multimorbidity , of these ADEs , i.e. both pADEs and ADRs . Methods : Adverse events experienced by patients admitted to two Dutch hospitals with functioning computerized physician order entry ( CPOE ) systems were prospect ively identified through chart review . Adverse events were divided into pADEs ( i.e. as a result of a medication error ) and non-preventable ADRs . In both cases , a causal relationship between adverse events and patients ’ drugs was established using the simplified Yale algorithm . Study data were collected anytime between April 2006 and May 2008 over a 5-month period at each hospital ward included in the study , beginning from 8 weeks after CPOE was implemented at the ward . Results : pADEs and non-preventable ADRs were experienced by 349 ( 58 % ) patients , of whom 307 ( 88 % ) had non-preventable ADRs . Multimorbidity ( adjusted odds ratio [ ORadj ] 1.90 ; 95 % CI 1.44,2.50 ; ORadj 1.28 ; 95 % CI 1.14 , 1.45 , respectively ) , length of stay ( ORadj 1.13 ; 95 % CI 1.06 , 1.21 ; ORadj 1.11 ; 95 % CI 1.07 , 1.16 , respectively ) , admission to the geriatric ward ( ORadj 7.78 ; 95 % CI 2.15 , 28.13 ; ORadj 3.82 ; 95 % CI 1.73 , 8.45 , respectively ) and number of medication orders ( ORadj 1.25 ; 95 % CI 1.16,1.35 ; ORadj 1.13 ; 95 % CI 1.06 , 1.21 , respectively ) were statistically significantly associated with pADEs and ADRs . Admission to the gastroenterology/rheumatology ward ( ORadj 0.22 ; 95 % CI 0.06 , 0.77 ; ORadj 0.40 ; 95 % CI 0.24 , 0.65 , respectively ) was inversely related to both pADEs and ADRs . Other determinants for ADRs only were female sex ( ORadj 1.77 ; 95 % CI 1.12 , 2.80 ) and use of drugs affecting the nervous system ( ORadj 1.83 ; 95 % CI 1.09 , 3.07 ) . Age was a significant determinant for pADEs only ( ORadj 1.07 ; 95 % CI 1.03 , 1.11 ) . Conclusions : In this study more than half of the patients admitted to the hospitals are harmed by drugs , of which most are non-serious , non-preventable ADRs ( after the introduction of CPOE ) . Determinants of both pADEs and ADRs overlap to a large extent . Our results imply the need for signalling early potential adverse events that occur during the normal use of drugs in multimorbid patients or those in geriatric wards . Subsequent therapeutic interventions may improve the well-being of hospitalized patients to a greater extent than focusing on errors in the medication process only Objective . The purpose of this study was to record prospect ively the frequency of medication order errors in a general hospital in Israel with the objective of assessing the impact of pharmacist intervention in preventing potential harm . Methods . The study was conducted during a 6‐month period . A total of 160 medication order errors were detected at the hospital of which 60.6 % were prescription errors and 39.4 % were therapy ones . Principal types of errors detected were incorrect dosage ( 27.5 % ) , interactions between drugs ( 20 % ) , incorrect drug ( 12.5 % ) , route ( 11.2 % ) and frequency ( 11.2 % ) . Medication error rate by degree of severity was calculated per 100 patient days . The highest rate was found in Hemato‐Oncology ( 2.48 ) , followed by Intensive Care ( 0.82 ) , Surgery ( 0.48 ) and Internal Medicine ( 0.26 ) . Anti‐infective drugs were the most prevalent class of drugs in which errors occurred ( 38.7 % ) followed by total parenteral nutrition preparations ( 21.8 % ) , antineoplastics ( 15.6 % ) and anticoagulants ( 11.3 % ) . Changes in medication orders due to pharmacists ' intervention only occurred in 73.8 % of error cases , most referring to dosage or route change ( 37.5 % ) . Conclusion . This study underestimates the actual number of medication errors . However , it identified problem areas and trends so that better measures to improve drug use could be implemented CONTEXT Iatrogenic injuries , including medication errors , are an important problem in all hospitalized population s. However , few epidemiological data are available regarding medication errors in the pediatric inpatient setting . OBJECTIVES To assess the rates of medication errors , adverse drug events ( ADEs ) , and potential ADEs ; to compare pediatric rates with previously reported adult rates ; to analyze the major types of errors ; and to evaluate the potential impact of prevention strategies . DESIGN , SETTING , AND PATIENTS Prospect i ve cohort study of 1120 patients admitted to 2 academic institutions during 6 weeks in April and May of 1999 . MAIN OUTCOME MEASURES Medication errors , potential ADEs , and ADEs were identified by clinical staff reports and review of medication order sheets , medication administration records , and patient charts . RESULTS We review ed 10 778 medication orders and found 616 medication errors ( 5.7 % ) , 115 potential ADEs ( 1.1 % ) , and 26 ADEs ( 0.24 % ) . Of the 26 ADEs , 5 ( 19 % ) were preventable . While the preventable ADE rate was similar to that of a previous adult hospital study , the potential ADE rate was 3 times higher . The rate of potential ADEs was significantly higher in neonates in the neonatal intensive care unit . Most potential ADEs occurred at the stage of drug ordering ( 79 % ) and involved incorrect dosing ( 34 % ) , anti-infective drugs ( 28 % ) , and intravenous medications ( 54 % ) . Physician review ers judged that computerized physician order entry could potentially have prevented 93 % and ward-based clinical pharmacists 94 % of potential ADEs . CONCLUSIONS Medication errors are common in pediatric inpatient setting s , and further efforts are needed to reduce them Introduction Medication errors in the intensive care unit ( ICU ) are frequent and lead to attributable patient morbidity and mortality , increased length of ICU stay and substantial extra costs . We investigated if the introduction of a computerized ICU system ( Centricity Critical Care Clinisoft , GE Healthcare ) reduced the incidence and severity of medication prescription errors ( MPEs ) . Methods A prospect i ve trial was conducted in a paper-based unit ( PB-U ) versus a computerized unit ( C-U ) in a 22-bed ICU of a tertiary university hospital . Every medication order and medication prescription error was vali date d by a clinical pharmacist . The registration of different classes of MPE was done according to the National Coordinating Council for Medication Error Reporting and Prevention guidelines . An independent panel evaluated the severity of MPEs . We identified three groups : minor MPEs ( no Output:	Conclusion A wide range of severity assessment tools are used in the literature . Developing a basis of comparison between tools would potentially be helpful in comparing findings across studies .
MS2981	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Obesity has a heritable component ; however , the heterogeneity of obesity complicates dissection of its genetic background . In this study , we therefore focused on eating patterns as specific traits within obesity . These traits have a heritable component ; genes associated with a specific eating pattern have not yet been reported at the population level . In this study , we determined whether genetic variations in cholecystokinin ( CCK ) and leptin genes underlie specific eating patterns . We selected obese individuals showing extreme snacking behavior or use of excessive portion sizes from a large population -based sample ( n = 17,357 ) from the Prospect -EPIC ( European Prospect i ve Study into Cancer and Nutrition ) study . Using allele-specific PCRs , we tested several single nucleotide polymorphisms in the c and i date genes and performed haplotype analysis . Obese carriers of common allelic variations in leptin or the leptin receptor gene had an increased risk to display extreme snacking behavior . In contrast , obese carriers of common allelic variations in CCK had an increased risk to eating increased meal sizes . In conclusion , we identified common allelic variants specifically associated with distinctly different eating patterns , namely extreme snacking behavior or excessive portion size Recent animal studies indicate that leptin is involved in the regulation of blood pressure through the leptin receptor . Therefore , 51-yr-old men ( N = 284 ) were selected ; and anthropometric , endocrine , metabolic , and hemodynamic variables were examined in relation to polymorphisms of the leptin receptor gene ( LEPR ) , by restriction fragment length polymorphism technique . Three polymorphisms were examined : Lys109Arg in exon 4 , Gln223Arg in exon 6 , and Lys656Asn in exon 14 . In comparison with Lys109 homozygotes , Arg109 homozygotes ( 9 % ) showed lower body mass index ( BMI ) and abdominal sagittal diameter , as well as lower systolic ( 10.0 mm Hg ) and diastolic ( 7.8 mm Hg ) blood pressure . Additionally , Arg223 homozygotes ( 26.8 % ) showed lower blood pressure ( 7.6/5.7 mm Hg ) than Gln223 homozygotes . These lower blood pressure levels were independent of other variables . No differences were found with the Lys656Asn polymorphism . Measurements of body fat mass correlated with leptin concentration in Lys109 homozygotes and in Lys109 heterozygotes but not in Arg109 homozygotes . Blood pressure correlated with leptin only in men carrying the wild-type allele Lys109 . With both elevated BMI and leptin , Lys109 homozygotes had higher blood pressure than the Arg109 homozygous men ( 12.4/6.9 mm Hg ) . Men with blood pressure > or = 140/90 mm Hg had , in comparison with normotensive men , increased BMI and leptin levels , and Lys109 homozygotes were significantly more prevalent . These results suggest that leptin is associated with blood pressure regulation in men through the leptin receptor . When BMI and leptin are elevated , increased blood pressure is found only with the most prevalent LEPR genotype at codons 109 and 223 , whereas variants of this receptor seem to protect from hypertension . This might explain why not all obese men are hypertensive We performed extensive and realistic simulations of the colonization process of Europe by Neolithic farmers , as well as their potential admixture and competition with local Palaeolithic hunter – gatherers . We find that minute amounts of gene flow between Palaeolithic and Neolithic population s should lead to a massive Palaeolithic contribution to the current gene pool of Europeans . This large Palaeolithic contribution is not expected under the demic diffusion ( DD ) model , which postulates that agriculture diffused over Europe by a massive migration of individuals from the Near East . However , genetic evidence in favour of this model mainly consisted in the observation of allele frequency clines over Europe , which are shown here to be equally probable under a pure DD or a pure acculturation model . The examination of the consequence of range expansions on single nucleotide polymorphism ( SNP ) diversity reveals that an ascertainment bias consisting of selecting SNPs with high frequencies will promote the observation of genetic clines ( which are not expected for r and om SNPs ) and will lead to multimodal mismatch distributions . We conclude that the different patterns of molecular diversity observed for Y chromosome and mitochondrial DNA can be at least partly owing to an ascertainment bias when selecting Y chromosome SNPs for study ing European population Output:	The meta- analysis of published data did not show an overall association between any of the tested LEPR variants and overweight . However , the choice of a BMI cut-off value to distinguish cases from controls was crucial to explain heterogeneity in Q223R . Differences in allele frequencies across ethnic groups are compatible with natural selection of derived alleles in Q223R and K109R and of the ancient allele in K656N in Asians . In CoLaus , the rs10128072 , rs3790438 and rs3790437 variants showed interaction with sex for their association with overweight , waist circumference and fat mass in linear regressions . Conclusions Our systematic review and analysis of primary data from the CoLaus study did not show an overall association between LEPR SNPs and overweight .
MS2982	*TASK* the task is to summarize an input biomedical literature in six sentences *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 reported 12 % incidence of acute renal failure after angiography prompted this prospect i ve study to substantiate or repudiate this seemingly excessive rate . In 537 consecutive patients undergoing cerebral , abdominal , or peripheral angiography , there was no instance of renal failure following the procedure . The results of this study indicate that when adequate hydration is maintained , angiography does not pose a " significant hazard " of renal failure as previously reported , even in patients with underlying medical problems BACKGROUND AND OBJECTIVES Most studies of contrast-induced acute kidney injury ( CIAKI ) have focused on patients undergoing angiographic procedures . The incidence and outcomes of CIAKI in patients undergoing nonemergent , contrast-enhanced computed tomography in the inpatient and outpatient setting were assessed . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS Patients with estimated glomerular filtration rates ( GFRs ) < 60 ml/min per 1.73 m(2 ) undergoing nonemergent computed tomography with intravenous iodinated radiocontrast at an academic VA Medical Center were prospect ively identified . Serum creatinine was assessed 48 to 96 h postprocedure to quantify the incidence of CIAKI , and the need for postprocedure dialysis , hospital admission , and 30-d mortality was tracked to examine the associations of CIAKI with these medical outcomes . RESULTS A total of 421 patients with a median estimated GFR of 53 ml/min per 1.73 m(2 ) were enrolled . Overall , 6.5 % of patients developed an increase in serum creatinine > or=25 % , and 3.5 % demonstrated a rise in serum creatinine > or=0.5 mg/dl . Although only 6 % of out patients received preprocedure and postprocedure intravenous fluid , < 1 % of out patients with estimated GFRs > 45 ml/min per 1.73 m(2 ) manifested an increase in serum creatinine > or=0.5 mg/dl . None of the study participants required postprocedure dialysis . Forty-six patients ( 10.9 % ) were hospitalized and 10 ( 2.4 % ) died by 30-d follow-up ; however , CIAKI was not associated with these outcomes . CONCLUSIONS Clinical ly significant CIAKI following nonemergent computed tomography is uncommon among out patients with mild baseline kidney disease . These findings have important implication s for providers ordering and performing computed tomography and for future clinical trials of CIAKI BACKGROUND Contrast-induced nephropathy ( CIN ) is a serious complication of percutenous coronary interventions ( PCI ) . Proper hydration reduces the risk of PCI . Wheter oral hydration is as effective as intravenous one has not been well established . AIM To determine the effects of oral hydration with mineral water versus intravenous hydration with isotonic solution ( 0.9 % NaCl ) on renal function in diabetic patients undergoing coronary angiography and angioplasty . METHODS The study included 102 patients ( age 67 ± 7.8 years , 44 female/58 male ) . Eligible patients ( group 1 - 52 pts ) were hydrated intravenously ( 1 mL/kg/h ) 6 hours before and during 12 hours following PCI with isotonic solution ( 0.9 % NaCl ) . Fifty patients ( group 2 ) were r and omised to receive oral mineral water ( 1 mL/kg/h ) 6 - 12 hours before and during 12 hours following angiography or angioplasty . All patients during the procedure received contrast medium ioversol . Primary endpoint of the study was the evaluation of renal function before and 72 hours after contrast medium administration . RESULTS Baseline creatinine clearance was 70.3 ± 21.22 mL/min in group 1 and 78.69 ± 19.92 mL/min in group 2 ( NS ) . The mean volume of contrast medium was 101.1 ± 36.7 mL in group 1 and 110.4 ± 45.3 mL in group 2 ( NS ) . At 72 hours after the procedure , creatinine clearance was 65.3 ± 23.39 mL/min in group 1 and 73.5 ± 21.94 mL/min in group 2 ( NS ) . CONCLUSIONS Our study demonstrates that the oral hydration with mineral water and intravenous hydration with 0.9 % NaCl have similar effects on renal function in diabetic patients undergoing coronary angiography and angioplasty BACKGROUND Contrast nephropathy ( CN ) is a common cause of renal dysfunction that may be prevented by saline hydration and by drugs such as theophylline or furosemide . Whether oral saline hydration is as efficient as intravenous saline hydration is unknown . The preventive efficacy of theophylline and furosemide for CN remains controversial . The purpose of the current study was to evaluate the efficacy of oral saline hydration and of intravenous saline hydration plus theophylline or furosemide for the prevention of CN . METHODS We prospect ively studied 312 patients with chronic renal failure ( serum creatinine 201+/-81 micromol/l , Cockcroft clearance 37+/-12 ml/min/1.73 m(2 ) ) , who were undergoing various radiological procedures with a non-ionic , low osmolality contrast agent . Patients were r and omly assigned to four arms . In arm A , patients received 1 g/10 kg of body weight/day of sodium chloride per os for 2 days before the procedure . In arm B , patients received 0.9 % saline intravenously at a rate of 15 ml/kg for 6 h before the procedure . In arm C , patients received the same saline hydration as in arm B plus 5 mg/kg theophylline per os in one dose 1 h before the procedure . In arm D , patients received the same saline hydration as in arm B plus 3 mg/kg of furosemide intravenously just after the procedure . RESULTS Patients were well-matched with no significant differences at baseline in any measured parameters . Acute renal failure , defined as an increase in serum creatinine of 44 micromol/l ( 0.5 mg/dl ) , occurred in 27 out of 312 patients ( 8.7 % ) . There was no significant difference between the rate of renal failure in the different arms of the study : five out of 76 ( 6.6 % ) in arm A , four out of 77 ( 5.2 % ) in arm B , six out of 80 ( 7.5 % ) in arm C and 12 out of 79 ( 15.2 % ) in arm D. No patient had fluid overload or a significant increase in blood pressure in the 2 days following the radiological procedure . The independent predictors of CN were diabetes mellitus , high baseline serum creatinine and high systolic blood pressure . CONCLUSIONS Oral saline hydration was as efficient as intravenous saline hydration for the prevention of CN in patients with stage 3 renal diseases . Furosemide and theophylline were not protective 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 OBJECTIVES The effects of an oral rehydration solution ( ORS ) on fatigue were studied in workers engaged in manual work during the summer . METHODS One hundred and fifty-three workers engaged in loading cargo onto aircraft at Tokyo International Airport who consented to participate in the study were the subjects . The study was carried out on two summer days with fine weather during the daytime shift . The subjects were r and omly divided into two groups : with one group restricted to ORS intake and the other group having free-choice of their favorite drink ( FAD ) in a r and omized crossover study . The subjects were asked about the amount of beverage that they consumed and the type of FAD that they chose on the days of the survey . The effects of the ORS and the FAD were compared using a visual analogue scale ( VAS ) to determine the degree of fatigue experienced immediately after completing work . RESULTS The average wet bulb globe temperature ( WBGT ) on the survey days was 30 degrees C. The beverage intake during work was 1,000 ml for most participants and the most commonly chosen types of FAD were tea and coffee . The fatigue VAS was significantly lower on the ORS intake days than on the FAD intake days ( 50.0 + /- 18.3 vs. 53.9 + /- 16.3 ) . CONCLUSIONS The results of this study suggest that the intake of ORS during outdoor work in a hot environment would be effective for preventing industrial accidents and heat stroke . It is important to select an appropriate drink to ensure adequate intake of water and electrolytes Despite myriad improvements in the care of hospitalized patients , a decline in renal function remains a common event . Renal function in 4,622 consecutive patients admitted to the medical and surgical services of an urban tertiary care hospital was followed up prospect ively from the time of admission . Some degree of renal insufficiency developed in 7.2 % of patients . Decreased renal perfusion , medications , surgery , and radiographic contrast media were the most common causes of hospital-acquired renal insufficiency ( HARI ) . The overall mortality rate was 19.4 % and was similar among patients for all causes of renal insufficiency , except sepsis . For patients with a greater than 3.0-mg/dL increase in serum creatinine level , the mortality rate was 37.8 % . As shown by previous investigators , age and preexisting renal insufficiency were risk factors for HARI . Women and blacks had less hospital-acquired renal failure . The increasing acuity of hospital admissions has been accompanied by a greater incidence of acute renal insufficiency in patients admitted to hospitals . There is a trend toward better survival in patients with a severe deterioration in renal function BACKGROUND AND OBJECTIVES No prospect i ve study has reported the incidence of contrast-induced nephropathy ( CIN ) or the associated morbidity and mortality after contrast-enhanced computed tomography ( CECT ) in the outpatient setting . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS We enrolled and followed a prospect i ve , Output:	La plupart des essais traitant de prévention des néphropathies secondaire aux PCI ont été effectués en context e d’administration artérielle , comme par cathétérisme cardiaque , et non d’administration veineuse , comme par tomodensitométrie . Les conclusions secondaires se rapportent à la sécurité et font part , entre autres , d’une comparaison des effets indésirables de l’administration orale d’eau salée et de l’administration intraveineuse de solution saline isotonique . Discussion Les résultats de cet essai pilote fourniront de l’information cruciale pour la planification de l’essai définitif visant à tester l’efficacité des voies d’administration des traitements de prévention d’IRA après les tomodensitométries avec agent de contraste
MS2983	*TASK* the task is to summarize an input biomedical literature in six sentences *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 effects of manual therapy and stretching exercise on neck pain and disability . DESIGN An examiner-blinded r and omized cross-over trial . PATIENTS A total of 125 women with non-specific neck pain . METHODS PATIENTS were r and omized into 2 groups . Group 1 received manual therapy twice weekly and Group 2 performed stretching exercises 5 times a week . After 4 weeks the treatments were changed . The follow-up times were after 4 and 12 weeks . Neck pain ( visual analogue scale ) and disability indices were measured . RESULTS Mean value ( st and ard deviation ) for neck pain was 50 mm ( 22 ) and 49 mm ( 19 ) at baseline in Group 1 and Group 2 , respectively , and decreased during the first 4 weeks by 26 mm ( 95 % Confidence Interval 20 - 33 ) and 19 mm ( 12 - 27 ) , respectively . There was no significant difference between groups . Neck and shoulder pain and disability index decreased significantly more in Group 1 after manual therapy ( p=0.01 ) as well as neck stiffness ( p=0.01 ) . CONCLUSION Both stretching exercise and manual therapy considerably decreased neck pain and disability in women with non-specific neck pain . The difference in effectiveness between the 2 treatments was minor . Low-cost stretching exercises can be recommended in the first instance as an appropriate therapy intervention to relieve pain , at least in the short-term OBJECTIVE This study evaluates the effectiveness of traditional bone setting ( TBS ) in chronic neck pain ( cNP ) compared with conventional physiotherapy ( PT ) and massage ( M ) . METHODS This was a r and omized clinical trial . Working-aged employed subjects with cNP ( n = 105 ; 37 men and 68 women ; mean age , 41.5 years ) were r and omized into TBS , PT , and M groups . Follow-up times were 1 , 6 , and 12 months after the treatments . Neck pain intensity ( visual analog scale ) , perceived disability ( Neck Disability Index [ NDI ] ) , and neck spine mobility measurements were used as outcomes . Global assessment was evaluated by the subjects ( scale from -1 to + 10 ) . Data were analyzed using time ( pre and post ) by group ( TBS , PT and M ) , 2- way analysis of variance for repeated measures . RESULTS Neck pain decreased and NDI scores improved in all groups 1 month after the treatment ( P < .001 ) . The improvement of NDI and persons ' satisfaction were significantly better after TBS . Neck spine mobility in rotation movements tended to improve significantly better and the frons-knee distance improved more after TBS . One year later , both NDI and neck pain were significantly better after TBS than in reference groups . A significant improvement was reported by 40 % to 45.5 % of subjects in the PT and M groups and by 68.6 % in the TBS group . Bone setters ' ability to communicate and to interact with patients was evaluated significantly higher . In the TBS group , the number of sick days was minimal as was the use of painkillers during 1-year follow-up compared to that in the reference groups . CONCLUSIONS Traditional bone setting , which is a soft manual mobilization technique focusing on the muscles , joints , and ligaments , appears to be effective in cNP . Two thirds of subjects experienced it as beneficial , and it seems to be able to improve disability and pain in patients with cNP . Subjective and partially objective benefits of TBS were found in those patients more than after other interventions , and the effects lasted at least for 1 year The existing review s of massage therapy ( MT ) research are either limited to infants , adults , or were conducted prior to the publication of the most recent studies using pediatric sample s. R and omized controlled trials ( RCTs ) of pediatric MT are review ed . A literature search yielded 24 RCTs of pediatric MT , defined as the manual manipulation of soft tissue intended to promote health and well-being in recipients between 2 and 19 years of age . Because RCTs of pediatric MT varied considerably in the amount and types of data reported , quantitative and narrative review methods were both used . Singledose and multiple-dose effects were examined separately . Among single-dose effects , significant reductions of state anxiety were observed at the first session ( g 1⁄4 0.59 , P < 0.05 ) and the last session ( g 1⁄4 1.10 , P < 0.01 ) of a course of treatment . Effects for salivary cortisol ( g 1⁄4 0.28 ) , negative mood ( g 1⁄4 0.52 ) and behavior ( g 1⁄4 0.37 ) were non-significant . Three of eleven multiple-dose effects were statistically significant . These were trait anxiety ( g 1⁄4 0.94 , P < 0.05 ) , muscle tone ( g 1⁄4 0.90 , P < 0.01 ) and arthritis pain ( g1⁄4 1.33 , P < 0.01 ) . Results of studies not permitting effect size calculation were judged to be generally consistent with quantitative results . MT benefits pediatric recipients , though not as universally as sometimes reported . Numerous weaknesses endemic to MT research ( e.g. low statistical power , frequent failure to report basic descriptive statistics ) are identified , and recommendations for future pediatric MT research are discussed Abstract Objectives : To compare the efficacy of acupuncture and conventional massage for the treatment of chronic neck pain . Design : Prospect i ve , r and omised , placebo controlled trial . Setting : Three outpatient departments in Germany . Participants : 177 patients aged 18–85 years with chronic neck pain . Interventions : Patients were r and omly allocated to five treatments over three weeks with acupuncture ( 56 ) , massage ( 60 ) , or “ sham ” laser acupuncture ( 61 ) . Main outcome measures : Primary outcome measure : maximum pain related to motion ( visual analogue scale ) irrespective of direction of movement one week after treatment . Secondary outcome measures : range of motion ( 3D ultrasound real time motion analyser ) , pain related to movement in six directions ( visual analogue scale ) , pressure pain threshold ( pressure algometer ) , changes of spontaneous pain , motion related pain , global complaints ( seven point scale ) , and quality of life ( SF-36 ) . Assessment s were performed before , during , and one week and three months after treatment . Patients ' beliefs in treatment were assessed . Results : One week after five treatments the acupuncture group showed a significantly greater improvement in motion related pain compared with massage ( difference 24.22 ( 95 % confidence interval 16.5 to 31.9 ) , P=0.0052 ) but not compared with sham laser ( 17.28 ( 10.0 to 24.6 ) , P=0.327 ) . Differences between acupuncture and massage or sham laser were greater in the subgroup who had had pain for longer than five years ( n=75 ) and in patients with myofascial pain syndrome ( n=129 ) . The acupuncture group had the best results in most secondary outcome measures . There were no differences in patients ' beliefs in treatment . Conclusions : Acupuncture is an effective short term treatment for patients with chronic neck pain , but there is only limited evidence for long term effects after five treatments . What is already known on this topic Acupuncture is a widespread complementary treatment Evidence from trials have given conflicting results on its use in the treatment of neck pain because of method ological shortcomings and because effects were compared either with alternative treatments or with different sham procedures imitating acupuncture , but not both What this study adds Compared with sham laser acupuncture and massage , needle acupuncture has beneficial effects on mobility and pain related to motion in patients with chronic neck pain Acupuncture was clearly more effective than massage , but differences were not always significant compared with sham laser acupuncture Acupuncture was the best treatment for patients with the myofascial syndrome and those who had had pain for longer than five Objectives Little is known about the effectiveness of therapeutic massage , one of the most popular complementary medical treatments for neck pain . A r and omized controlled trial was conducted to evaluate whether therapeutic massage is more beneficial than a self-care book for patients with chronic neck pain . Methods Sixty-four such patients were r and omized to receive up to 10 massages over 10 weeks or a self-care book . Follow-up telephone interviews after 4 , 10 , and 26 weeks assessed outcomes including dysfunction and symptoms . Log-binomial regression was used to assess whether there were differences in the percentages of participants with clinical ly meaningful improvements in dysfunction and symptoms ( ie , > 5-point improvement on the Neck Disability Index ; > 30 % improvement from baseline on the symptom bothersomeness scale ) at each time point . Results At 10 weeks , more participants r and omized to massage experienced clinical ly significant improvement on the Neck Disability Index [ 39 % vs. 14 % of book group ; relative risk (RR)=2.7 ; 95 % confidence interval ( CI ) , 0.99 - 7.5 ] and on the symptom bothersomeness scale ( 55 % vs. 25 % of book group ; RR=2.2 ; 95 % CI , 1.04 - 4.2 ) . After 26 weeks , massage group members tended to be more likely to report improved function ( RR=1.8 ; 95 % CI , 0.97 - 3.5 ) , but not symptom bothersomeness ( RR=1.1 ; 95 % CI , 0.6 - 2.0 ) . Mean differences between groups were strongest at 4 weeks and not evident by 26 weeks . No serious adverse experiences were reported . Conclusions This study suggests that massage is safe and may have clinical benefits for treating chronic neck pain at least in the short term . A larger trial is warranted to confirm these results Study Design . Population ‐based , cross‐sectional mailed survey . Objective . To determine the lifetime , period , and point prevalence of neck pain and its related disability among Saskatchewan adults and investigate the presence and strength of nonresponse bias . Summary of Background Data . In Europe , the life‐time and point prevalence of neck pain is almost as high as the prevalence of low back pain . Similarly , chronic neck pain is highly prevalent and a common source of disability in the working‐age population . However , no studies specifically have documented the prevalence of neck pain and its related disability in North America . Methods . The Saskatchewan Health and Back Pain Survey was mailed to 2184 r and omly selected Saskatchewan adults aged 20‐69 years . Fifty‐five percent of the study population participated . The presence of nonresponse bias was investigated through logistic regression and wave analysis . The Chronic Pain Question naire was used to classify the severity of chronic neck pain . Results . The age‐st and ardized lifetime prevalence of neck pain is 66.7 % ( 95 % confidence interval , 63.8‐69.5 ) , and the point prevalence is 22.2 % ( 95 % confidence interval , 19.7‐24.7 ) . The age‐st and ardized 6‐month prevalence of low‐intensity and low‐disability neck pain is 39.7 % ( 95 % confidence interval , 36.7‐42.7 ) , whereas it is 10.1 % ( 95 % confidence interval , 8.2‐11.9 ) for high‐intensity and low‐disability neck pain and 4.6 % ( 95 % confidence interval , 3.3‐5.8 ) for significantly disabling neck pain . The prevalence of low‐intensity and low‐disability neck pain decreases with age . More women experience high‐disability neck pain than men . Wave analysis suggests that the point prevalence and 6‐month prevalence of high‐intensity and low‐disability neck pain are overestimated in this survey . Conclusion . This cross‐sectional study shows that neck pain is highly prevalent in Saskatchewan and that it significantly disables 4.6 % ( 95 % confidence interval , 3.3‐5.8 ) of the adult population BACKGROUND Neck pain is one of the most common musculoskeletal ailments . The aim of this study was to evaluate the effectiveness and impact of therapeutic massage on the range of motion in patients with neck pain . MATERIAL AND METHODS The study involved 60 patients aged 37 - 82 years ( mean age : 62.8 ± 9.86 years ) treated for neck pain at the Rehabilitation Department of Zamość University of Management and Administration . The patients were divided into two groups : one ( 30 persons ) received kinesiotherapy and physiotherapy , and the other group ( 30 persons ) additionally received therapeutic massage . The effectiveness of rehabilitation was assessed with a Saunders digital inclinometer , the Neck Disability Index ( NDI ) and a Visual Analogue Scale ( VAS ) . RESULTS Both groups did not differ significantly in terms of NDI and VAS scores at baseline ( NDI : p = 0.56 , VAS : P = 0.231 ) and after rehabilitation ( NDI : p = 0.203 ; VAS : P = 0.401 ) . The NDI question naire and VAS revealed a significant pain reduction ( p < 0.001 ) , and improved performance and function ( p < 0.001 ) after rehabilitation in both groups . Patients who had received massage demonstrated a statistically significant improvement in the range of flexion ( p = 0.022 ) , lateral bend to the right ( p = 0.018 ) , and lateral bend to the left ( p = 0.003 ) . CONCLUSIONS 1 Output:	There was no valid evidence of MT on improving dysfunction . With regard to follow-up effects , there was not enough evidence of MT for neck pain . This systematic review found moderate evidence of MT on improving pain in patients with neck pain compared with inactive therapies and limited evidence compared with traditional Chinese medicine . There were no valid lines of evidence of MT on improving dysfunction .
MS2984	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Total hip or knee replacement is highly successful when judged by prosthesis-related outcomes . However , some people experience long-term pain . Objectives To review published studies in representative population s with total hip or knee replacement for the treatment of osteoarthritis reporting proportions of people by pain intensity . Data sources MEDLINE and EMBASE data bases search ed to January 2011 with no language restrictions . Citations of key articles in ISI Web of Science and reference lists were checked . Study eligibility criteria , participants and interventions Prospect i ve studies of consecutive , unselected osteoarthritis patients representative of the primary total hip or knee replacement population , with intensities of patient-centred pain measured after 3 months to 5-year follow-up . Study appraisal and synthesis methods Two authors screened titles and abstract s. Data extracted by one author were checked independently against original articles by a second . For each study , the authors summarised the proportions of people with different severities of pain in the operated joint . Results Search es identified 1308 articles of which 115 reported patient-centred pain outcomes . Fourteen articles describing 17 cohorts ( 6 with hip and 11 with knee replacement ) presented appropriate data on pain intensity . The proportion of people with an unfavourable long-term pain outcome in studies ranged from about 7 % to 23 % after hip and 10 % to 34 % after knee replacement . In the best quality studies , an unfavourable pain outcome was reported in 9 % or more of patients after hip and about 20 % of patients after knee replacement . Limitations Other studies reported mean values of pain outcomes . These and routine clinical studies are potential sources of relevant data . Conclusions and implication s of key findings After hip and knee replacement , a significant proportion of people have painful joints . There is an urgent need to improve general awareness of this possibility and to address determinants of good and bad outcomes OBJECTIVE To evaluate the association between vitamin C supplementation and the incidence and progression of radiographic knee osteoarthritis ( OA ) . DESIGN Prospect i ve cohort study . SETTING Clearwater Osteoarthritis Study ( COS ) : ( 1988 to the present ) a longitudinal study . SUBJECTS Male and female COS participants aged 40 years and above ( n 1023 ) . The study exposure was the participants ' self-reported history of vitamin C supplementation . The participants underwent biennial , sequential knee radiographs , which were assessed using the Kellgren-Lawrence ordinal scale to determine evidence of the study 2 outcomes : incident radiographic knee OA ( RKOA ) and progression of RKOA . RESULTS Individuals without baseline knee OA who self-reported vitamin C supplement usage were 11 % less likely to develop knee OA than were those individuals who self-reported no vitamin C supplement usage ( risk ratio (RR)=0.89 , 95 % CI 0.85 , 0.93 ) . Among those participants with RKOA at baseline , vitamin C supplement usage did not demonstrate an association with RKOA progression ( RR=0.94 , 95 % CI 0.79 , 1.22 ) . CONCLUSIONS In the present prospect i ve cohort study , we found no evidence to support a protective role of vitamin C in the progression of knee OA . However , after controlling for confounding variables , these data suggest that vitamin C supplementation may indeed be beneficial in preventing incident knee OA . Given the massive public health burden of OA , the use of a simple , widely available and inexpensive supplement to potentially reduce the impact of this disease merits further consideration OBJECTIVE To evaluate the symptomatic effects of highly purified chondroitin 4 and chondroitin 6 sulfate ( CS ) therapy in patients with osteoarthritis ( OA ) of the h and . METHODS This investigator-initiated , single-center , r and omized , double-blind , placebo-controlled clinical trial included 162 symptomatic patients with radiographic evidence of h and OA ( American College of Rheumatology criteria ) . Inclusion criteria included patient 's assessment of global spontaneous h and pain of at least 40 mm on a 0 - 100-mm visual analog scale ( VAS ) and functional impairment of at least 6 ( 0 - 30 scale ) on the Functional Index for H and OA ( FIHOA ) in the most symptomatic h and . Patients received either 800 mg of CS ( n = 80 patients ) or placebo ( n = 82 patients ) once daily for 6 months and were analyzed in an intent-to-treat approach . The two primary outcomes were the change in the patient 's assessment of global spontaneous h and pain and in h and function ( by FIHOA score ) from baseline to month 6 . Secondary outcomes were improvement in grip strength , duration of morning stiffness , acetaminophen consumption , and the investigator 's global impression of treatment efficacy . RESULTS There was a significantly more pronounced decrease in the patient 's global assessment of h and pain in the CS group than in the placebo group ( difference VAS scores -8.7 mm ; P = 0.016 ) . H and function improved significantly more in the CS group than in the placebo group ( difference in FIHOA scores -2.14 ; P = 0.008 ) . There was a statistically significant between-group difference in favor of CS for the duration of morning stiffness and for the investigator 's global impression of treatment efficacy . Changes in grip strength , acetaminophen consumption , and safety end points were not significantly different between the two groups . CONCLUSION This study demonstrates that CS improves h and pain and function in patients with symptomatic OA of the h and and shows a good safety profile OBJECTIVE To investigate whether early changes in biochemical markers of bone ( NTX-I ) and cartilage ( CTX-II [ C-terminal crosslinking telopeptide of type II collagen ] ) degradation are associated with radiological progression in patients with knee osteoarthritis ( OA ) receiving risedronate . DESIGN Two thous and four hundred and eighty three patients with medial compartment knee OA were r and omized in two 24-month studies in North America ( NA ) and European Union ( EU ) . Studies evaluated risedronate 5 mg/day , 35 mg/week ( EU ) , 50 mg/week ( NA ) , and 15 mg/day ( NA and EU ) , compared to placebo in reducing signs and symptoms and in slowing radiographic progression . One thous and eight hundred and eighty five patients from the pooled EU and NA studies with available NTX-I/CTX-II at both baseline and 6 months and radiographs at baseline and at 24 months were analyzed . RESULTS Risedronate produced a dose-dependent reduction of NTX-I and CTX-II observed at 6 months which continued up to 24 months . Patients who had CTX-II levels returned to low levels ( < 150 ng/mmol creatinine ) at 6 months had a lower risk of radiographic progression at 24 months than patients whose CTX-II levels were increased both at baseline and 6 months [ odds-ratio ( 95 % confidence interval ) : 0.57 ( 0.39 - 0.85 ) after adjustment for demographics and joint space width ] . The lowest risk of progression was observed in patients who had low CTX-II levels both at baseline and at 6 months [ odds-ratio 0.36 ( 0.21 - 0.63 ) ] . No significant association between NTX-I levels and radiological progression was observed . CONCLUSION CTX-II decreased with risedronate in patients with knee OA and levels reached after 6 months were associated with radiological progression at 24 months . Monitoring a marker of cartilage degradation 6 months after initiating treatment may be instructive in identifying patients with low progression Objective To determine the effect of chondroitin sulphate ( CS ) treatment on cartilage volume loss , subchondral bone marrow lesions ( BML ) , synovitis and disease symptoms in patients with knee osteoarthritis ( OA ) . Methods In this pilot multicentre , r and omised , double-blind , controlled trial in primary knee OA , 69 patients with clinical signs of synovitis were r and omised to receive CS 800 mg or placebo once daily for 6 months followed by an open-label phase of 6 months in which patients in both groups received CS 800 mg once daily . Cartilage volume and BML were assessed by MRI at baseline and at 6 and 12 months ; synovial membrane thickness was assessed at baseline and at 6 months . Results The CS group showed significantly less cartilage volume loss than the placebo group as early as 6 months for the global knee ( p=0.030 ) , lateral compartment ( p=0.015 ) and tibial plateaus ( p=0.002 ) , with significance persisting at 12 months . Significantly lower BML scores were found for the CS group at 12 months in the lateral compartment ( p=0.035 ) and the lateral femoral condyle ( p=0.044 ) . Disease symptoms were similar between the two groups . Conclusion CS treatment significantly reduced the cartilage volume loss in knee OA starting at 6 months of treatment , and BML at 12 months . These findings suggest a joint structure protective effect of CS and provide new in vivo information on its mode of action in knee OA Background Knee osteoarthritis ( OA ) is a major cause of pain and functional limitation in older adults , yet longer-term studies of medical treatment of OA are limited . Objective To evaluate the efficacy and safety of glucosamine and chondroitin sulphate ( CS ) , alone or in combination , as well as celecoxib and placebo on painful knee OA over 2 years . Methods A 24-month , double-blind , placebo-controlled study , conducted at nine sites in the US ancillary to the Glucosamine/chondroitin Arthritis Intervention Trial , enrolled 662 patients with knee OA who satisfied radiographic criteria ( Kellgren/Lawrence grade 2 or 3 changes and baseline joint space width of at least 2 mm ) . This subset continued to receive their r and omised treatment : glucosamine 500 mg three times daily , CS 400 mg three times daily , the combination of glucosamine and CS , celecoxib 200 mg daily , or placebo over 24 months . The primary outcome was a 20 % reduction in Western Ontario and McMaster University Osteoarthritis Index ( WOMAC ) pain over 24 months . Secondary outcomes included an Outcome Measures in Rheumatology/Osteoarthritis Research Society International response and change from baseline in WOMAC pain and function . Results Compared with placebo , the odds of achieving a 20 % reduction in WOMAC pain were celecoxib : 1.21 , glucosamine : 1.16 , combination glucosamine/CS : 0.83 and CS alone : 0.69 , and were not statistically significant . Conclusions Over 2 years , no treatment achieved a clinical ly important difference in WOMAC pain or function as compared with placebo . However , glucosamine and celecoxib showed beneficial but not significant trends . Adverse reactions were similar among treatment groups and serious adverse events were rare for all treatments Background The implementation of evidence based clinical practice guidelines on self-management interventions to patients with chronic diseases is a complex process . A multifaceted strategy may offer an effective knowledge translation ( KT ) intervention to promote knowledge uptake and improve adherence in an effective walking program based on the Ottawa Panel Evidence Based Clinical Practice Guidelines among individuals with moderate osteoarthritis ( OA ) . Methods A single-blind , r and omized control trial was conducted . Patients with mild to moderate ( OA ) of the knee ( n=222 ) were r and omized to one of three KT groups : 1 ) Walking and Behavioural intervention ( WB ) ( 18 males , 57 females ) which included the supervised community-based aerobic walking program combined with a behavioural intervention and an educational pamphlet on the benefits of walking for OA ; 2 ) Walking intervention ( W ) ( 24 males , 57 females ) wherein participants only received the supervised community-based aerobic walking program intervention and the educational pamphlet ; 3 ) Self-directed control ( C ) ( 32 males , 52 females ) wherein participants only received the educational pamphlet . One-way analyses of variance were used to test for differences in quality of life , adherence , confidence , and clinical outcomes among the study groups at each 3 month assessment during the 12-month intervention period and 6-month follow-up period . Results Short-term program adherence was greater in WB compared to C ( p<0.012 ) after 3 months . No statistical significance ( p > 0.05 ) was observed for long-term adherence ( 6 to 12 months ) , and total adherence between the three groups . The three knowledge translation strategies demonstrated equivalent long-term results for the implementation of a walking program for older individuals with moderate OA . Lower dropout rates as well as higher retention rates were observed for WB at 12 and 18 months . Conclusion The additional knowledge translation behavioural component facilitated the implementation of clinical practice guidelines on walking over a short-term period . More studies are needed to improve the long-term walking adherence or longer guidelines uptake on walking among participants with OA . Particular attention should be taken into account related to patient ’s characteristic and preference . OA can be managed through the implementation of a walking program based on clinical practice guidelines in existing community-based walking clubs as well as at home with the minimal support of an exercise therapist or a trained volunteer . Trial Registration Current Controlled Trials OBJECTIVE Synovitis is very common in knee OA and associated with pain . This open- Output:	RESULTS Both " strong " and " conditional " recommendations are given for management of h and , hip , and knee OA and nonpharmacological , pharmacological , and surgical modalities of treatment are presented according to the different levels of agreement .
MS2985	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Blood pressure can be determined more precisely with the use of 24 hours ambulatory measurement in type 1 diabetics . Nitric oxide ( NO ) has been suggested to be responsible for the vascular changes described in early diabetic nephropathy . We aim ed to investigate serum NO concentration along with ambulatory blood pressure monitoring ( ABPM ) parameters in type 1 diabetic patients and to find out whether there are correlation between serum NO level and ABPM parameters . Forty type 1 diabetic subjects and 35 controls were enrolled . Diabetic subjects were grouped as microalbuminuric ( n=16 ) and normalbuminuric ( n=24 ) . Casual and ambulatory blood pressure parameters and serum NO concentrations were measured in all study population . Microalbuminuric subjects had higher nighttime systolic blood pressure ( SBP ) , 24 hours diastolic blood pressure ( DBP ) and 24 hours mean arterial pressure ( MAP ) than controls . Both microalbuminuric and normalbuminuric subjects had also significantly higher nighttime DBP and nighttime MAP than controls . Serum NO concentrations were higher in normalbuminuric and microalbuminuric subjects than controls . Serum NO concentrations were positively correlated with daytime DBP and MAP , nighttime SBP , DBP and MAP , and 24 hours DBP and MAP in microalbuminuric subjects . Serum NO concentrations were also positively correlated with nighttime DBP in normalbuminuric subjects . Multiple linear regression analysis revealed that serum NO(2)- + NO(3)- concentrations and 24 hours DBP were independently associated with the development of microalbuminuria . Albuminuria seems to be closely associated with serum NO concentrations and ABPM parameters in type 1 DM patients . A prospect i ve follow-up study on diabetic patients with normo- and micro- albuminuria is needed to confirm the predictive values of increased NO concentrations and ABPM parameters on the development of albuminuria Abstract . Recently , an international consensus paper was published for st and ardization of home self-blood pressure ( BP ) measurement in adults . However , few data exist regarding home BP measurement in children , although it is recommended for all pediatric patients on renal replacement therapy in Germany . Therefore , a survey was performed among German-speaking pediatric nephrologists ( members of the Arbeitsgemeinschaft Pädiatrische Nephrologie ) in order to study their opinions about home blood pressure measurements . Approximately 75 % of German pediatric nephrology centers responded to the survey . More than 70 % of the interviewees prescribed a blood pressure device for all children with renal diseases and hypertension or on renal replacement therapy . For children with antihypertensive medication , 2.8 daily measurements were recommended at mean and 2.2 measurements for children without therapy . Auscultation of Korotkoff sounds and oscillometric BP measurements were used in the same percentage for home BP recordings . The upper cut of level for home blood pressure values was rated by the pediatric nephrologists and compared to reference values of casual blood pressure . There was good agreement for upper systolic BP , but as many as 40 to 50 % of the interviewees accepted upper diastolic BP values higher than the 97th percentile for casual BP . Home BP measurement was judged to be more important than office BP measurement by 64 % of the nephrologists and less important than 24 h ambulatory blood pressure monitoring by 67 % . The results of the survey showed wide discrepancies for st and ards of home BP measurement in children and adolescents , especially for the recommendations for upper diastolic BP . Before home blood pressure measurements can be recommended unrestrictedly in children and adolescents , we stress the need for st and ardization of blood pressure devices and measurement . Prospect i ve studies in children are needed to demonstrate that these st and ards facilitate better prediction of cardiovascular outcome using home BP measurements compared to office BP recordings in children Whereas the diurnal fall of BP ( dipping ) is an important prognostic marker in patients with chronic renal failure ( CRF ) , the integrity of physiologic ultradian ( i.e. , shorter than 24 h ) cardiovascular rhythms in patients with CRF is unknown . Also , the relationship between conventional dipping analysis and Fourier spectral rhythm analysis has not been examined in renal hypertension . The prevalence and dimensions of the circadian and three ultradian ( 12 , 8 , and 6 h ) cardiovascular rhythms were studied by ambulatory BP monitoring in 214 children ( aged 3 to 18 yr ) with CRF ( stage 2 to 4 chronic kidney disease ) and no antihypertensive treatment compared with 938 healthy control subjects , and the relationship of rhythm characteristics to conventional dipping parameters , renal function , proteinuria , and serum electrolytes was assessed . The CRF cohort exhibited significantly reduced amplitudes of the circadian and all ultradian cardiovascular rhythms studied ( all P < 0.01 ) . Moreover , all BP and most heart rate rhythms showed significantly delayed acrophases ( time of peak ; P < 0.01 ) . Whereas conventional BP dipping parameters ( day/night difference , day/night ratio ) and the 24-h BP amplitude were independent of renal function , the 8-h BP amplitude was positively correlated with GFR ( r = 0.3 , P = 0.01 ) and inversely correlated with the urinary protein/creatinine ratio ( r = -0.27 , P < 0.05 ) , and the 6-h BP amplitude was inversely correlated with proteinuria ( r = -0.3 , P < 0.02 ) . Children who displayed 24- or 12-h cardiovascular rhythms had significantly lower serum calcium levels than children without these rhythms . In summary , children with CRF display not only blunted circadian but also blunted ultradian cardiovascular rhythms . Ultradian but not circadian rhythms or conventional dipping parameters are quantitatively associated with renal function and proteinuria BACKGROUND Left-ventricular hypertrophy ( LVH ) is a risk factor for cardiovascular morbidity . Antihypertensive treatment with angiotensin-converting enzyme inhibitors ( ACEI ) is able to induce the regression of LVH in adults . However , there has been no study of the ability of ACEI to induce the regression of LVH in children . Our aim was to investigate the effect of ramipril on left-ventricular mass and blood pressure ( BP ) in hypertensive children . METHODS Twenty-one children ( median age , 15 years ) with renal ( 76 % ) or primary ( 24 % ) hypertension were prospect ively treated with ramipril monotherapy for 6 months . Blood pressure was evaluated using ambulatory BP monitoring , with hypertension defined as mean BP > or=95th percentile . Left-ventricular hypertrophy was defined either as left-ventricular mass index ( LVMI ) > 38.6 g/m(2.7 ) ( pediatric definition ) or as LVMI > 51.0 g/m(2.7 ) ( adult definition ) . RESULTS Nineteen children completed the study . The median LVMI decreased from 36.8 g/m(2.7 ) ( range , 18.9 to 55.8 g/m(2.7 ) ) to 32.6 g/m(2.7 ) ( range , 19.0 to 52.1 g/m(2.7 ) ; P < .05 ) after 6 months . The prevalence of LVH decreased from 42 % to 11 % using the pediatric definition ( P < .05 ) and did not change using the adult definition ( ie , it remained at 5 % ) . The median ambulatory BP decreased by 11 , 7 , 8 , and 7 mm Hg for daytime systolic , daytime diastolic , nighttime systolic , and nighttime diastolic BP ( P < .05 ) , respectively . A positive correlation was found between LVMI and nighttime systolic BP at the start of the study ( r = 0.46 , P < .05 ) . CONCLUSIONS Ramipril is an effective drug in children with hypertension , for its ability to reduce not only BP but also left-ventricular mass and induce regression of LVH Background : Hypertension is a frequent complication of end-stage renal disease and left ventricular hypertrophy ( LVH ) is common in patients with poorly controlled hypertension . The aim of this study was to evaluate hypertension in pediatric peritoneal dialysis ( PD ) patients , to compare casual and ambulatory blood pressure ( BP ) measurements and to evaluate the impact of BP parameters on LVH . Methods : The study comprised 25 PD patients ( 9 M , 16 F ; mean age 14.14 ± 3.32 years ) that have been followed in outpatient clinics . Medical records were review ed for demographic features ; casual BP measurements , ambulatory blood pressure monitoring ( ABPM ) and echocardiographic evaluation were applied to all patients . Results : The mean 24-hour and daytime systolic blood pressure ( SBP ) values were found to be higher than casual SBP ( p < 0.001 ) . Significant difference was present in the frequency of hypertension between casual SBP ( 32 % ) and the mean daytime SBP ( 56 % ) ( p < 0.05 ) . Nighttime systolic hypertension was detected in 14 ( 56 % ) and diastolic hypertension in 16 ( 64 % ) patients . Elevated daytime SBP load and DBP load were detected in 64 and 76 % of the patients , respectively . Elevated nighttime SBP load and DBP load were detected in 72 % of the patients . Seventeen ( 68 % ) patients had attenuated dipping for SBP . The mean left ventricular mass index ( LVMI ) was 52.65 ± 18.17 g/m2.7 and 13 ( 52 % ) patients had LVH . LVMI was significantly correlated with casual BP measurements and the majority of ABPM parameters . Conclusion : The majority of pediatric PD patients had BP abnormalities in which severity was most accurately assessed with ABPM . Casual BP and majority of ABPM parameters were found to be significantly correlated with LVMI . Ambulatory blood pressure monitoring should be performed in all pediatric PD patients BACKGROUND Angiotensin-converting enzyme inhibitors are the drugs of choice in renal hypertension . The efficacy and safety of ramipril in adults has been proved ; however , data on effectiveness of ramipril in children are few . The aim of the present study was to investigate the effect of ramipril on blood pressure ( BP ) and proteinuria in children with chronic kidney diseases . METHODS A total of 31 children ( median age 11.3 years , range 1.9 - 19.8 years ) with various chronic nephropathies and hypertension or proteinuria were prospect ively treated with ramipril for 6 months . Blood pressure was evaluated using ambulatory BP monitoring and hypertension was defined as mean BP equal to or greater than the 95th percentile for healthy children . Proteinuria was defined as protein excretion > or = 100 mg/m(2)/24 h. The starting dose of ramipril was 1.5 mg/m(2)/24 h once daily . In 27 children it was given as monotherapy . RESULTS The median decrease in ambulatory BP was 11 mm Hg for daytime systolic , 10 mm Hg for daytime and nighttime diastolic , and 8 mm Hg for nighttime systolic BP . Hypertension normalized in 55 % of the children . Proteinuria decreased in 84 % of the children with pathologic proteinuria ; the median decrease was 51 % . A positive correlation was found between initial proteinuria and change of proteinuria ( r = 0.95 , P < .001 ) . Glomerular filtration rate and serum potassium level did not change significantly . One child developed a cough that was believed to be related to ramipril . CONCLUSIONS Ramipril is an effective and safe drug in children with chronic kidney diseases associated with hypertension , proteinuria , or both BACKGROUND While the antihypertensive and renoprotective potency of angiotensin-converting enzyme ( ACE ) inhibitors is well-established in adults with hypertension and /or chronic renal failure , little experience exists in pediatric chronic kidney disease . METHODS As part of a prospect i ve assessment of the renoprotective efficacy of ACE inhibition and intensified blood pressure ( BP ) control , 397 children ( ages 3 to 18 years ) with chronic renal failure [ CRF ; glomerular filtration rate ( GFR ) 11 to 80 mL/min/1.73 m2 ] and elevated or high-normal BP received ramipril ( 6 mg/m2 ) following a 6-month run-in period including a two-month washout of any previous ACE inhibitors . Drug efficacy was assessed by two monthly office BP and proteinuria assessment s , and by ambulatory BP monitoring at start and after 6 months of treatment . RESULTS In the 352 patients completing six months of treatment , 24-hour mean arterial pressure ( MAP ) had decreased by a mean of 11.5 mm Hg ( -2.2 SDS ) in initially hypertensive subjects , but only by 4.4 mm Hg ( -0.8 SDS ) in patients with initially normal BP . A linear correlation was found between MAP at baseline and the change of MAP during treatment ( r= 0.51 ; P < 0.0001 ) . The antihypertensive response was independent of changes in concomitant Output:	The available evidence suggests a moderate but significant association between ambulatory BP and pre clinical organ damage , mainly based on studies in nephropathy and /or diabetes .
MS2986	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To determine the effects of four doses of a 7-day transdermal 17beta-estradiol ( E2 ) delivery system , including 0.025 mg/day , on bone loss in postmenopausal women . METHODS This was a multicenter , double-masked , r and omized , placebo-controlled study of the effects of transdermal E2 at doses of 0.025 , 0.05 , 0.06 , and 0.1 mg/day for the prevention of postmenopausal osteoporosis . Efficacy was evaluated from bone mineral density of lumbar vertebrae L2-L4 , radius , proximal femur , and total hip measured with dual-energy x-ray absorptiometry . Serum osteocalcin and urinary pyridinoline and deoxypyridinoline concentrations were measured . RESULTS At 24 months , E2 doses of 0.025 , 0.05 , 0.06 , and 0.1 mg/day result ed in mean increases in bone mineral density of the lumbar spine of 2.37 % , 4.09 % , 3.28 % , and 4.70 % , respectively , and increased bone mineral density of the total hip by 0.26 % , 2.85 % , 3.05 % , and 2.03 % , respectively . All increases were statistically significantly greater than placebo , which decreased bone mineral density by 2.49 % at the spine and 2.04 % at the hip . Consistent and significant improvements in biochemical markers of bone turnover also were noted at various intervals in all treatment groups . The most frequent adverse events were local reactions from the transdermal drug-delivery system , effects of estrogen , and menopausal symptoms . CONCLUSION Transdermal E2 at doses of 0.025 , 0.05 , 0.06 , and 0.1 mg/day effectively prevented bone loss in postmenopausal women A 10-year , double-blind prospect i ve study was undertaken to evaluate the effects of estrogen replacement therapy . The sample population consisted of 84 pairs of r and omly chosen postmenopausal patients who were matched for age and diagnosis . One half of the patients received conjugated estrogens and cyclic progesterone , while the other half received placebo . Estrogen-treated patients whose therapy started within 3 years of menopause showed improvement or no increase in osteoporosis . Control patients demonstrate an increase in their osteoporosis Postmenopausal hormone replacement therapy is associated with a reduction in the incidence of coronary heart disease . However , inconclusive results have been reported with respect to the risk of stroke , and recent studies consistently showed an increased risk of venous thromboembolism in postmenopausal women using oral estrogen . There are surprisingly few interventional studies to assess the true effects of estrogen-progestin regimens on blood coagulation and fibrinolysis , and the impact of the route of estrogen administration on hemostasis has not been well documented . Therefore , we investigated the effects of oral and transdermal estradiol/progesterone replacement therapy on hemostatic variables . Forty-five healthy postmenopausal women , aged 45 to 64 years , were assigned r and omly to one of the three following groups : cyclic oral or transdermal estradiol , both combined with progesterone , or no hormonal treatment . Hemostatic variables were assayed at baseline and after a 6-month period . Pairwise differences in the mean change between the three groups were compared using nonparametric tests . Oral but not transdermal estradiol regimen significantly increased the mean value of prothrombin activation peptide ( F1 + 2 ) and decreased mean antithrombin activity compared with no treatment . Differences in fragment F1 + 2 levels between active treatments were significant . The oral estrogen group was associated with a significant decrease in both mean tissue-type plasminogen ( t-PA ) concentration and plasminogen activator inhibitor ( PAI-1 ) activity and a significant rise in global fibrinolytic capacity ( GFC ) compared with the two other groups . A transdermal estrogen regimen had no significant effect on PAI-1 , t-PA , and GFC levels . There were no significant changes in mean values of fibrinogen , factor VII , von Willebr and factor , protein C , fibrin D-dimer , and plasminogen between and within the three groups . We conclude that oral estrogen/progesterone replacement therapy may result in coagulation activation and increased fibrinolytic potential , whereas opposed transdermal estrogen appears without any substantial effects on hemostasis . Whereas these results may account for an increased risk of venous thromboembolism in users of oral postmenopausal estrogen , they emphasize the potential importance of the route of estrogen administration in prescribing hormone replacement therapy to postmenopausal women , especially to those at high risk of thrombotic disease CONTEXT Therapy with individual antiresorptive agents has been shown to be effective for prevention and treatment of postmenopausal osteoporosis , but whether combination antiresorptive therapy with hormones and bisphosphonates is safe or efficacious or how these agents compare in elderly women is unknown . OBJECTIVE To determine whether hormone replacement and the bisphosphonate alendronate sodium in combination are efficacious and safe , and how they compare with monotherapy in community-dwelling elderly women . DESIGN R and omized , double-blind , placebo-controlled , clinical trial . SETTING AND PARTICIPANTS Five hundred seventy-three community-dwelling women age 65 years or older were screened : 485 completed screening and 373 ( aged 65 to 90 years ) were r and omized following a 3-month , open-label , run-in phase with hormone replacement and alendronate placebo . The trial was conducted at a single academic US medical center from January 1996 to May 2001 . INTERVENTIONS Participants were r and omly assigned in a 2 x 2 factorial design to receive hormone replacement ( conjugated equine estrogen , 0.625 mg/d , with or without medroxyprogesterone , 2.5 mg/d ) and alendronate , 10 mg daily , both agents , or neither . All participants received calcium and vitamin D supplements . MAIN OUTCOME MEASURES Annualized change in bone mineral density of the hip and spine and occurrence of adverse events . RESULTS Bone mineral density at 3 years was significantly greater at all femoral and vertebral sites in women treated with combination therapy than with monotherapy , with mean ( SD ) increases of 5.9 % ( 3.8 ) at the total hip , 10.4 % ( 5.4 ) at the posteroanterior lumbar spine , and 11.8 % ( 6.8 ) at the lateral lumbar spine . Mean ( SD ) increases in bone mass at the hip in women treated with alendronate alone were significantly greater than in those treated with hormone replacement therapy alone ( 4.2 % [ 3.8 ] vs 3.0 % [ 4.9 ] ; P<.05 , respectively ) , and alendronate result ed in more responders to therapy . All therapies were well tolerated and participant retention was 90 % at 3 years . CONCLUSIONS Combination therapy with hormone replacement and alendronate was efficacious and well tolerated in this cohort . Alendronate was superior to hormone replacement , and combination therapy was superior to either therapy alone . Combination therapy may represent an option for women with more severe disease or for those who have failed to achieve an adequate response to monotherapy BACKGROUND Long-term treatment of patients with asymptomatic primary hyperparathyroidism remains controversial , but the presence of osteoporosis is regarded as an indication for parathyroidectomy . Hormone replacement therapy ( HRT ) is a possible alternative therapy in osteopenic postmenopausal women with the disorder , and results of short-term studies suggest a beneficial effect on bone mass comparable to that achieved by parathyroidectomy . Longer-term data are required to further assess the efficacy of this treatment in chronic stable primary hyperparathyroidism . METHODS We report the results of the extension from 2 to 4 years of a r and omized , placebo-controlled trial of HRT in postmenopausal women with primary hyperparathyroidism . Of 23 postmenopausal women with primary hyperparathyroidism , 11 received active HRT with conjugated equine estrogen , 0.625 mg/d , and medroxyprogesterone acetate , 5 mg/d , and 12 received placebo . Bone mineral density was measured throughout the skeleton at 6-month intervals using dual-energy x-ray absorptiometry in these women and in 50 normocalcemic age-matched control subjects . None of the 23 patients withdrew during the extension period . RESULTS Changes in bone mineral density were more positive in those taking HRT than placebo , with the between-group differences at 4 years being 4.6 % in the total body , 7.5 % in the lumbar spine , 7.4 % in the femoral neck , 8.2 % in the femoral trochanter , 6.8 % in the legs , and 7.0 % in the forearm ( P<.01 ) . At skeletal sites composed predominantly of cortical bone , there was a progressive divergence of the 2 groups . Biochemical markers of bone turnover remained lower throughout the study in women taking HRT . When rates of bone loss were compared between the placebo group and healthy women of comparable age , bone loss tended to be more marked throughout the skeleton in women with hyperparathyroidism , but only in the total body and its legs subregion was this difference significant . CONCLUSIONS Hormone replacement therapy is efficacious in the long-term management of osteopenia in postmenopausal women with primary hyperparathyroidism and thus represents an important new therapeutic option for asymptomatic patients who do not have other indications for surgery . Bone loss seems to be accelerated in untreated primary hyperparathyroidism BACKGROUND We conducted a 3-year , double-blind , r and omized , placebo-controlled study to determine whether the positive effects of hormone/estrogen replacement therapy ( H/ERT ) on postcranial bone density are accompanied by similar positive effects on oral bone mass . METHODS A total of 135 postmenopausal women ( aged 41 - 70 years ) with no evidence of moderate or severe periodontal disease were r and omized to receive daily oral conjugated estrogen ( Premarin ; 0.625 mg ) alone or in combination with medroxyprogesterone acetate ( Prempro ; 0.625 and 2.5 mg , respectively ) or placebo . All subjects received calcium carbonate ( 1000 mg/d ) and cholecalciferol ( 400 [ corrected ] IU/d ) supplements . The primary efficacy end points were the changes in alveolar crest height and alveolar bone density . Alveolar crest height was measured on bite-wing radiographs , and changes in alveolar bone mass were assessed by means of digital-subtraction radiography . Postcranial bone density was measured in the lumbar spine and left proximal femur by means of dual-energy x-ray absorptiometry . RESULTS Hormone/estrogen replacement therapy significantly increased alveolar bone mass compared with placebo ( + 1.84 % vs + 0.95 % [ P = .04 ] ) , and tended to improve alveolar crest height ( + 4.83 % vs + 3.46 % [ P = .34 ] ) . Bone mineral density of the proximal femur significantly increased in the H/ERT compared with the placebo group ( total proximal femur , + 3.59 % vs + 0.22 % [ P = .001 ] ; neck , + 2.05 % vs -0.34 % [ P = .02 ] ; trochanter , + 3.49 % vs + 0.08 % [ P<.001 ] ) , but not the lumbar spine ( + 1.01 % vs + 0.17 % [ P = .39 ] ) . Changes in alveolar bone mass correlated with bone density changes in the total femur ( r = 0.28 [ P = .02 ] ) and femoral trochanter ( r = 0.25 [ P = .04 ] ) in the H/ERT but not in the placebo group . CONCLUSIONS Postcranial and oral bone mass were increased in postmenopausal women receiving H/ERT . Improvement in oral bone health constitutes an additional benefit of H/ERT OBJECTIVE To determine the relative risk for sustaining a first hip fracture after hormone replacement therapy . DESIGN Prospect i ve population -based cohort study with an average observation period of 5.7 years . SETTING A prescription-based cohort in the Uppsala health care region in Sweden . PARTICIPANTS The cohort ( 23 246 women ) comprised virtually all women of 35 years of age and older who received noncontraceptive estrogens from April 1977 through March 1980 . Comparisons were made with women in the background population . MEASUREMENTS Follow-up through 1983 was done with regard to hospital admissions for a first cervical or trochanteric hip fracture . The observed number of cases was compared with that expected on the basis of person-years of observation in the cohort and incidence rates in the background population . Analyses were made in exposure categories , based solely on prescription data . MAIN RESULTS During 133 022 person-years of observation , 163 cases of first Output:	No increase in the incidence of total cancer events but an increase in the incidence of thrombus was found to be associated with HT . Conclusions : HT is associated with a reduced risk of total , hip , and vertebral fractures , with a possible attenuation of this protection effect after it is stopped or when it is begun after 60 years . However , there may be an increase in the incidence of thrombus formation associated with HT
MS2987	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: There is increasing evidence that the biochemical and cellular phenomena induced by blood/ membrane/dialysate interactions contribute to dialysis-related intradialytic and long-term complications . However , there is a lack of large , prospect i ve , r and omized trials comparing biocompatible and bioincompatible membranes , and convective and diffusive treatment modalities . The primary aim of this prospect i ve , r and omized trial was to evaluate whether the use of polysulfone membrane with bicarbonate dialysate offers any advantage ( in terms of treatment tolerance , nutritional parameters and pre-treatment beta-microglobulin levels ) over a traditional membrane ( Cuprophan ) . A secondary aim was to assess whether the use of more sophisticated methods consisting of a biocompatible synthetic membrane with different hydraulic permeability at different ultrafiltration rate ( high-flux hemodialysis and hemodiafiltration ) offers any further advantages . Seventy-one Centers were involved and stratified according to the availability of only the first two or all four of the following techniques : Cuprophan hemodialysis ( Cu-HD ) , low-flux polysulfone hemodialysis ( LfPS-HD ) , high-flux polysulfone high-flux hemodialysis ( HfPS-HD ) , and high-flux polysulfone hemodiafiltration ( HfPS-HDF ) . The 380 eligible patients were r and omized to one of the two or four treatments ( 132 to Cu-HD , 147 to LfPS-HD , 51 to HfPS-HD and 50 to HfPS-HDF ) . The follow-up was 24 months . No statistical difference was observed in the algebraic sum of the end points between bicarbonate dialysis with Cuprophan or with low-flux polysulfone , or among the four dialysis methods under evaluation . There was a significant decrease in pre-dialysis plasma beta 2-microglobulin levels in high-flux dialysis of 9.04 + /- 10.46 mg/liter ( 23 % ) and in hemodiafiltration of 6.35 + /- 12.28 mg/liter ( 16 % ) , both using high-flux polysulfone membrane in comparison with Cuprophan and low-flux polysulfone membranes ( P = 0.032 ) . The significant decrease in pre-dialysis plasma beta 2-microglobulin levels could have a clinical impact when one considers that beta 2-microglobulin accumulation and amyloidosis are important long-term dialysis-related complications BACKGROUND Accumulation of larger molecular weight uraemic toxins molecules may have a negative effect on the cardiovascular and nutritional state of dialysis patients and influence uraemic symptomatology . Their clearance can be enhanced by the use of haemofiltration ( HF ) . METHODS The effects of low-flux haemodialysis ( HD ) ( ultrapure dialysate ; polyamide membranes ) and pre-dilution on-line HF ( 1:1 blood/substitution ratio ; target filtration volume : 1.2 times body weight ) on cardiovascular and nutritional parameters , interdialytic levels of uraemic toxins and quality of life ( QOL ; Laupacis question naire ) were assessed during 1 year follow-up . Forty patients were r and omized . RESULTS After 1 year , 27 patients were eligible for analysis ( HF : 13 patients ; HD : 14 patients ) . Left ventricular mass index did not change in the HF patients ( 127+/-33 -- > 131+/-36 g/m(2 ) after 12 months ) or in the HD group ( 135+/-34 -- > 138+/-32 g/m(2 ) ) . Also , there were no changes in pulse wave velocity , and 48 h systolic and diastolic blood pressures . Lean body mass , assessed by dual-energy X-ray absorptiometry , increased in the HF group ( 44.8+/-8.9 -- > 46.2+/-9.6 kg ; P<0.05 ) , but not in the HD group ( 49.4+/-9.2 -- > 50.6+/-8.8 kg ) , although differences between groups were not significant . Insulin-like growth factor-1 levels remained stable in the HF patients , but decreased in the HD group ( P<0.05 between groups ) . QOL for physical symptoms improved in the HF group ( 4.2+/-1.2 -- > 5.0+/-1.1 ; P<0.05 within the HF group and P = 0.06 between groups ) , but not in the HD group ( 4.0+/-1.0 -- > 4.4+/-1.4 ) . beta2-microglobulin , complement factor D and homocysteine decreased significantly in the HF but not in the HD group , whereas l-ADMA , leptin and advanced glycation end-products-related fluorescence did not change . CONCLUSIONS No changes in cardiovascular parameters were observed during pre-dilution on-line HF compared with low-flux HD . Treatment with on-line HF result ed in marked changes in the uraemic toxicity profile , an improvement in physical well-being and a small improvement in nutritional state Some of the morbidity associated with chronic hemodialysis is thought to result from retention of large molecular weight solutes that are poorly removed by diffusion in conventional hemodialysis . Hemodiafiltration combines convective and diffusive solute removal in a single therapy . The hypothesis that hemodiafiltration provides better solute removal than high-flux hemodialysis was tested in a prospect i ve , r and omized clinical trial . Patients were r and omized to either on-line postdilution hemodiafiltration or high-flux hemodialysis . The groups did not differ in body size , treatment time , blood flow rate , or net fluid removal . The filtration volume in hemodiafiltration was 21 + /-1 L. Therapy prescriptions were unchanged for a 12-mo study period . Removal of both small ( urea and creatinine ) and large ( ss(2)-microglobulin and complement factor D ) solutes was significantly greater for hemodiafiltration than for high-flux hemodialysis . The increased urea and creatinine removal did not result in lower pretreatment serum concentrations in the hemodiafiltration group . Pretreatment plasma beta(2)-microglobulin concentrations decreased with time ( P < 0.001 ) ; however , the decrease was similar for both therapies ( P = 0.317 ) . Pretreatment plasma complement factor D concentrations also decreased with time ( P<0.001 ) , and the decrease was significantly greater with hemodiafiltration than with high-flux hemodialysis ( P = 0.010 ) . The conclusion is that on-line hemodiafiltration provides superior solute removal to high-flux hemodialysis over a wide molecular weight range . The improved removal may not result in lower pretreatment plasma concentrations , however , possibly because of limitations in mass transfer rates within the body In patients with ESRD , the effects of online hemodiafiltration on all-cause mortality and cardiovascular events are unclear . In this prospect i ve study , we r and omly assigned 714 chronic hemodialysis patients to online postdilution hemodiafiltration ( n=358 ) or to continue low-flux hemodialysis ( n=356 ) . The primary outcome measure was all-cause mortality . The main secondary endpoint was a composite of major cardiovascular events , including death from cardiovascular causes , nonfatal myocardial infa rct ion , nonfatal stroke , therapeutic coronary intervention , therapeutic carotid intervention , vascular intervention , or amputation . After a mean 3.0 years of follow-up ( range , 0.4 - 6.6 years ) , we did not detect a significant difference between treatment groups with regard to all-cause mortality ( 121 versus 127 deaths per 1000 person-years in the online hemodiafiltration and low-flux hemodialysis groups , respectively ; hazard ratio , 0.95 ; 95 % confidence interval , 0.75 - 1.20 ) . The incidences of cardiovascular events were 127 and 116 per 1000 person-years , respectively ( hazard ratio , 1.07 ; 95 % confidence interval , 0.83 - 1.39 ) . Receiving high-volume hemodiafiltration during the trial associated with lower all-cause mortality , a finding that persisted after adjusting for potential confounders and dialysis facility . In conclusion , this trial did not detect a beneficial effect of hemodiafiltration on all-cause mortality and cardiovascular events compared with low-flux hemodialysis . On-treatment analysis suggests the possibility of a survival benefit among patients who receive high-volume hemodiafiltration , although this subgroup finding requires confirmation BACKGROUND Morbidity and mortality rates in diabetic patients on regular dialysis treatment ( RDT ) are higher than in non-diabetic-subjects on RDT . Moreover , diabetic patients experience an intradialitic morbidity unacceptably higher than in patients with other causes of terminal renal failure . The aim of the present investigation was to compare st and ard bicarbonate haemodialysis ( BHD ) with acetate-free biofiltration ( AFB ) in a group of 41 diabetic patients stable on dialysis treatment for 25 + /- 22 months . METHODS Twenty-four type II and 17 type I diabetic patients , all requiring insulin therapy , were included and were followed for 1 year in a 6-month cross-over r and omized study for both methods . The analysis was carried out on dialysis symptoms , interdialysis symptoms , and nutritional status , and the multivariate analysis of variance for repeated measures on the same subjects in the two techniques was used . RESULTS AFB significantly reduced dialytic and extradialytic symptoms ( P=0.003 and 0.001 respectively ) . Cardiovascular collapses decreased by 43 % , and other dialysis symptoms showed a similar trend ( -35 % ) . The interdialysis symptoms decreased by 28 % and were accompanied by an increase in subjective wellbeing ( 39 % ) when patients were switched from traditional haemodialysis to AFB . Acid base control was better with AFB ( P=0.01 ) , both at the beginning and during the session . Slightly significant differences were also obtained for Kt/V ( AFB 1.48 + /- 0.29 vs BHD 1.38 + /- 0.30 ) , while no significant difference was noted with respect to sodium mass balance , nutritional status , calorie-protein intake , nPCR , blood glucose profile , and insulin requirements . The number of hospital admissions and the mortality rate , which were much lower during the AFB than the BHD period , were not analysed statistically . CONCLUSIONS AFB allows better control of some metabolic aspects , reduces intra- and extradialysis symptoms , and improves patient quality of life . Whether the long-term prognosis can be improved by AFB remains to be established with further studies Chronic inflammation contributes to the pathogenesis of several complications of hemodialysis therapy . It is thought that backfiltration of bacteria-derived contaminations during dialysis may induce a chronic inflammatory state . High-sensitivity C-reactive protein ( hs-CRP ) is one of the tools which can take a hold on such a chronic inflammatory condition . We examined the effect of ultrapure dialysate which contributes to chronic inflammation with hs-CRP and tried to reduce endotoxin ( ET ) levels at the end of the dialysate from 70 EU/l to < 1.0 EU/l ( ultrapure dialysate ) . Other dialysis conditions , except ET level , were fixed . We investigated the hs-CRP of 23 patients receiving regular dialysis before the use of ultrapure dialysate and 1 year after use of it prospect ively . The data showed a significant decrease in the median value of the hs-CRP from 0.16 to 0.07 mg/dl ( p < 0.05 ) . The value of serum β2-microglobulin decreased from 33.2 to 28.4 mg/dl ( p < 0.01 ) and the hemoglobin level increased from 10.0 to 11.0 g/dl ( p < 0.05 ) . These results indicate that even a dialysate containing 70 EU/l of ET level may induce a chronic inflammatory state . hs-CRP is a very useful marker of chronic inflammation and the use of ultrapure dialysate is necessary to improve a chronic inflammatory state . The targeted ET level at the end of the dialysate should be set at ≤1.0 EU/l Background : Controlled r and omised studies to prove improved cardiovascular stability and improved anaemia management during on-line haemodiafiltration ( oHDF ) are scarce . Methods : 70 patients were treated with both haemodialysis ( HD ) and oHDF in a cross-over design during 2 × 24 weeks at a dialysis dose of eKt/V≧1.2 . Patients r and omised into group A started on HD and switched over to oHDF , whereas patients in group B began with oHDF and were treated with HD afterwards . Intradialytic morbid events ( IME ) , such as symptomatic hypotension or muscle cramps , were noted in case Output:	CONCLUSIONS Treatment effects of convective dialysis are unreliable due to limitations in trial methods and reporting . Convective dialysis may reduce cardiovascular but not all-cause mortality , and effects on nonfatal cardiovascular events and hospitalization are inconclusive
MS2988	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The purpose of the present study was to assess the effects of a 12-week aerobic and muscular strength training program on selected dance performance and fitness-related parameters in modern dance students . The sample consisted of 32 men and women ( age 19 ± 2.2 years ) who were r and omly assigned into exercise ( n = 19 ) and control ( n = 13 ) groups . Anthropometric and flexibility assessment s , treadmill ergometry , strength measurements , and —on a separate day — a dance technique test were conducted pre and postexercise training in both groups . After the end of the program , the exercise group revealed significant increases in dance ( p > 0.02 ) , & OV0312;O2max ( p > 0.04 ) , flexibility ( p > 0.01 ) , and leg strength ( p > 0.001 ) tests compared to controls . It is concluded that in modern dance students ( a ) a 3-month aerobic and strength training program has positive effects on selected dance performance and fitness-related parameters , ( b ) aerobic capacity and leg strength improvements do not hinder dance performance as studied herein , and ( c ) the dance-only approach does not provide enough scope for physical fitness enhancements PURPOSE The aim of this study was to generate and vali date a prediction equation for estimating the body composition in dancers using the bioelectrical impedance analysis ( BIA ) as a method of assessment . METHODS The fat-free mass ( FFM ) of 42 young female professional dance students was estimated by four different methods : dual x-ray absorptiometry ( DXA ) , BIA , simple anthropometry , and skinfold thickness ; DXA was used as a criterion method . RESULTS The dancers ' FFM was 42.6 kg ( SD : 3.3 ) and , on the average , body fat represented the 19.4 % ( SD : 4.3 ) of their body weight . Two dancer-specific BIA equations for the prediction of FFM ( E(BIA ) ) were developed by multiple regression analysis using weight , height , resistance index , and triceps as predictor variables ( E(BIA ) and E(BIA-TRICEPS ) ) . The validity of these equations as well as of those previously reported was assessed in two r and omly selected subgroups of the initial study group , as described by the Bl and -Altman analysis . The bias and the limits of agreement of the equations developed in the present study were lower than those result ing from the application of the previously used equations of Segal et al. and Hergenroeder et al. It was also found that , when vali date d against DXA , skinfolds measurements did not accurately predict body fatness in this group of young females . CONCLUSION The new equations allow for an accurate routine assessment of body composition in young female dancers by using the method of BIA . Further studies are needed for the cross-validation of the equations in various groups of dancers OBJECTIVES To compare the hip and ankle range of motion and hip muscle strength in 8 - 11 year old novice female ballet dancers and controls . METHODS Subjects were 77 dancers and 49 controls ( mean ( SD ) age 9.6 ( 0.8 ) and 9.6 ( 0.7 ) years respectively ) . Supine right active hip external rotation ( ER ) and internal rotation ( IR ) were measured using an inclinometer . A turnout protractor was used to assess st and ing active turnout range . The measure of ER achieved from below the hip during turnout ( non-hip ER ) was calculated by subtracting hip ER range from turnout range , and hip ER : IR was derived by dividing ER range by IR range . Range of right weight bearing ankle dorsiflexion was measured in a st and ing lunge using two methods : the distance from the foot to the wall ( in centimetres ) and the angle of the shank to the vertical via an inclinometer ( in degrees ) . Right calf muscle range was measured in weight bearing using an inclinometer . A manual muscle tester was used to assess right isometric hip flexor , internal rotator , external rotator , abductor , and adductor strength . RESULTS Dancers had less ER ( p<0.05 ) and IR ( p<0.01 ) range than controls but greater ER : IR ( p<0.01 ) . Although there was no difference in turnout between groups , the dancers had greater non-hip ER . Dancers had greater range of ankle dorsiflexion than controls , measured in both centimetres ( p<0.01 ) and degrees ( p<0.05 ) , but similar calf muscle range . After controlling for body weight , controls had stronger hip muscles than dancers except for hip abductor strength which was similar . Regression analyses disclosed a moderate relation between turnout and hip ER ( r = 0.40 ) . There were no significant correlations between range of motion and training years and weekly training hours . CONCLUSIONS Longitudinal follow up will assist in determining whether or not hip and ankle range in young dancers is genetically fixed and unable to be improved with further balletic training This study evaluated the body composition ( underwater weighing ) and cardiorespiratory function ( VO(2)max and O(2)debt max measured by the treadmill exercise test ) in 12 members of the women 's volleyball team ( mean age 17.4 years ) and 11 members of the women 's basketball team ( mean age 17.6 years ) that won the championship in the Japan Inter-high School Meeting . We also examined differences in the physical abilities between the members of the top teams of different events . The following results were obtained . ( 1 ) The mean values of the height and body weight were 168.7+/-5.89 cm and 59.7+/-5.73 kg in the volleyball players and 166.5+/-7.87 cm and 58.8+/-6.85 kg in the basketball players . ( 2 ) The mean % Fat was 18.4+/-3.29 % in the volleyball players and 15.7+/-5.05 % in the basketball players , and was similar to the reported values in elite adult players . ( 3 ) The mean VO(2)max was 2.78+/-0.32 L x min(-1 ) ( 46.5+/-2.90 ml x kg(-1 ) x min(-1 ) ) in the volleyball players and 3.32+/-0.31 L x min(-1 ) ( 56.7+/-4.17 ml x kg(-1 ) x min(-1 ) ) in the basketball players , and was similar to the reported values in elite adult players . ( 4 ) The mean O(2)debt max was 6.18+/-1.15 L ( 103.2+/-12.40 ml x kg(-1 ) ) in the volleyball players and 7.92+/-1.80 L ( 134.3+/-23.24 ml x kg(-1 ) ) in the basketball players . These values were 2.6 times and 3.3 times as high as the average values in high school students in general . ( 5 ) No significant difference was observed in any measured item of the physique , skinfold thickness , or body composition between the volleyball players and basketball players . ( 6 ) The VO(2)max and O(2)debt max were 22 % and 28 % higher in the basketball players than in the volleyball players . From these results , the female volleyball players and basketball players evaluated in this study had the physical abilities needed to win the championship in the Japan Inter-high School Meets , i.e. a large FFM and excellent aerobic and anaerobic work capacities . Also , basketball appears to require higher aerobic and anaerobic work capacities than volleyball & NA ; Wyon , M.A. , A. Grant , E. Redding , A. Head , and N.C.C. Sharp . Oxygen uptake during modern dance class , rehearsal , and performance . J. Strength Cond . Res . 18(3):646–649 . 2004.—The aim of the present study was to examine whether the workload , expressed in oxygen uptake and heart rate , during dance class and rehearsal prepared the dancer for performance . Previous research on the dem and s of class and performance has been affected by equipment limitations and could only provide limited insight into the physiological dem and s placed on the dancer . The present study noted that dance performance had significantly greater mean oxygen uptake and heart rate than noted in both class and rehearsal ( p < 0.05 ) . Further analysis noted that , during class and rehearsal , heart rates were rarely within the aerobic training zone ( 60–90%HRmax , where HRmax is the maximum heart rate ) . Dance performance placed a greater dem and on the aerobic and anaerobic glycolytic energy systems than seen during class and rehearsal , which placed a greater emphasis on the adenosine triphosphate‐creatine phosphate system . Practical implication s suggest the need to supplement training within dance companies to overcome this deficit in training dem and BACKGROUND Carried out to investigate cardiovascular and metabolic response during various gymnastic routines [ Pommel Horse ( PH ) , Roman Ring ( RR ) , Parallel Bar ( PB ) , Horizontal Bar ( HB ) and Floor Exercise ( FE ) ] . METHODS EXPERIMENTAL DESIGN comparative and r and omized . SETTING General purpose , applicable on gymnastics training . Participants . Five male volunteers drawn from students attending sports coaching course in gymnastics at NIB , Patiala . A mixed population from all over India who had competitive experience of 6 to 10 years . INTERVENTIONS no interventions . MEASURES presence of heart rate overshooting , high lactate levels and individual characteristics of the gymnastics routines . RESULTS In all the routines peak HR was much lower than maximum heart rate ( HRmax ) of the gymnasts . Mean HR was lowest in first set and highest in the final ( 3rd set ) on all the apparatuses . Highest mean HR was recorded in HB followed by FE , RR , PB and PH respectively . After both first and third sets blood lactic acid ( La ) was highest in FE followed by RR , PB , HB and PH . La levels following the first set were 7.11 , 6.77 , 6.23 , 5.97 and 5.18 mM/l , respectively . Third set values were 10.54 , 10.16 , 8.95 , 8.74 and 8.04 mM/l . CONCLUSIONS ( a ) Cardiovascular load in various gymnastic routines is considerably less than maximal running ; ( b ) HR overshoot is common at the end of all the men 's gymnastic routines ; training evaluation or performance evaluation in gymnastics through heart rate should consider this fact to avoid any misinterpretation ; ( c ) PH is physiologically least dem and ing among the five while FE and RR are most stressful ; ( d ) repetition of gymnastic exercise routines with short rest pause may lead the gymnast to reach nearer to his lactate tolerance ; ( e ) gymnastics activity is dominated by anaerobic metabolism Output:	At a professional level , it appears that contemporary dancers demonstrate higher maximal oxygen uptake and higher scores in muscular endurance than ballet dancers . However , contemporary dance students are equally fit compared to their ballet counterparts and their body composition is also very similar . Further research is needed in order to confirm preliminary data , which suggest that the implementation of additional fitness training is beneficial for contemporary dance students to achieve a better performance outcome
MS2989	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Preliminary reports in patients with Parkinson 's disease ( PD ) showed that subthalamic nucleus ( STN ) stimulation was able to reverse parkinsoniam state . Since 1998 we evaluated the safety and the efficacy of STN stimulation in 7 patients affected by advanced PD . All patients were included using CAPIT protocol . Motor functions and quality of life were evaluated , before and after surgery , with UPDRS and PDQ38 , respectively . At the 6-month follow-up , the off medication/on stimulation UPDRS motor score improved by 50.6 % and the on medication/on stimulation by 20.3 % . Motor fluctuations were reduced by 57.2 % and dyskinesias by 73.5 % . The total D-dopa equivalent daily dose was reduced by 40.7 % . PDQ38 ameliorated by 49.9 % . We did not observe any perioperatory complication and only mild and tolerable side effects after stimulation A series of 24 consecutive PD patients were prospect ively studied prior to and within 6 months postoperatively for mood , motor , and cognitive status to investigate the effects on mood of subthalamic deep brain stimulation ( DBS ) in PD . In six patients ( 25 % ) , mood state worsened significantly , and three were transiently suicidal despite clear motor improvement . Caregivers and patients should be educated about the potential impact of this neurosurgical procedure on mood OBJECTIVE To evaluate the effects of bilateral deep brain stimulation in the subthalamic nucleus for symptomatic relief of advanced idiopathic Parkinson 's disease . DESIGN Prospect i ve cohort study . SETTING Patients were assessed and received medical treatment at the Kingston Centre , Southern Health , Melbourne . Surgery took place at Melbourne Neuroscience Centre , The Royal Melbourne Hospital . Both are tertiary public institutions . SUBJECTS 14 patients with Parkinson 's disease with intact cognition and difficult to manage motor symptoms who were referred to Kingston Centre between 1996 and 2000 and were eligible for surgical intervention . INTERVENTIONS All patients were assessed both after 12 hours ' withdrawal from and while taking their levodopa medication on two occasions before surgery . Further assessment s were carried out one , three , six and 12 months after surgery . MAIN OUTCOME MEASURES The Unified Parkinson 's Disease Rating Scale motor exam and gait parameters , such as stride length and velocity , were compared at six months after surgery with neither stimulation nor medication , with stimulation only , with medication only , and with stimulation and medication . RESULTS Stimulators were explanted in one patient after intracranial haemorrhage and relocated to the thalamus in a second . Extraneous factors prevented two patients from attending at six-month follow-up . Motor performance improved significantly with stimulation alone in the 10 remaining patients . Further significant gains were seen with stimulation and medication combined , with an apparent reduction in side-effects such as dyskinesia . CONCLUSIONS Bilateral deep brain stimulation of the subthalamic nucleus significantly improves motor performance in advanced Parkinson 's disease , despite a rather high complication rate OBJECTIVES Deep brain stimulation of the basal ganglia has become a promising treatment option for patients with Parkinson 's disease who have side effects from drugs . Which is the best target — globus pallidus internus ( GPi ) or subthalamic nucleus (STN)—is still a matter of discussion . The aim of this prospect i ve study is to compare the long term effects of GPi and STN stimulation in patients with severe Parkinson 's disease . PATIENTS AND METHODS Bilateral deep brain stimulators were implanted in the GPi in six patients and in the STN in 12 patients with severe Parkinson 's disease . Presurgery and 3 , 6 , and 12 months postsurgery patients were scored according to the CAPIT protocol . RESULTS Stimulation of the STN increased best Schwab and Engl and scale score significantly from 62 before surgery to 81 at 12 months after surgery ; GPi stimulation did not have an effect on the Schwab and Engl and scale . Stimulation of the GPi reduced dyskinesias directly whereas STN stimulation seemed to reduce dyskinesias by a reduction of medication . Whereas STN stimulation increased the unified Parkinson 's disease rating scale ( UPDRS ) motor score , GPi stimulation did not have a significant effect . Fluctuations were reduced only by STN stimulation and STN stimulation suppressed tremor very effectively . CONCLUSION Stimulation of the GPi reduces medication side effects , which leads to a better drug tolerance . There was no direct improvement of bradykinesia or tremor by GPi stimulation . Stimulation of the STN ameliorated all parkinsonian symptoms . Daily drug intake was reduced by STN stimulation . The STN is the target of choice for treating patients with severe Parkinson 's disease who have side effects from drugs Background The main advantage of deep brain stimulation ( DBS ) in the treatment of PD is that the electrical setting s can be adjusted to optimize benefits and minimize adverse effects . The main objective of this study was to discover how varying these electrical parameters impacted on parkinsonian motor signs . Methods Twelve patients with PD with chronic bilateral subthalamic nucleus ( STN ) stimulation were selected . The authors evaluated the effects of a variation in the voltages , frequencies , and pulse widths on tremor , bradykinesia , and rigidity using two different paradigms : one in which the total electrical energy delivered was held constant , and one in which this was varied . Up to 26 parameter conditions were tested under double blind r and omized conditions . Results Voltages ≥3 V and frequencies ≥130 Hz led to the greatest improvement in all three parkinsonian signs . A rate of 5 Hz significantly worsened akinesia . The combination of the highest voltage with the narrowest pulse width was most effective . Conclusions This study confirms that the most beneficial effects induced by STN stimulation are obtained at high frequencies and that voltage is the most critical factor to obtain adequate alteration in STN activity . The mechanisms by which STN DBS improves parkinsonism remain speculative Abstract Bilateral deep brain stimulation is an effective treatment for most motor signs of Parkinson 's disease ( PD ) , but the effects on cognitive functions are less clear . We therefore examined the effects of bilateral deep brain stimulation on central information processing , using the event-related auditory P300 potential as an electrophysiological index of mental chronometry . Eight PD patients with bilateral stimulators within the subthalamic nuclei ( STN ) and eight age-matched controls participated . Patients were examined after overnight withdrawal of antiparkinson medication , both “ on ” and “ off ” stimulation ( in r and om sequence ) . The P300 and reaction times were recorded using an auditory oddball paradigm . P300 latencies were prolonged in PD patients off stimulation ( 440 ± 45 ms ) compared to controls ( 397 ± 16 ms ; P < 0.05 ) . STN stimulation significantly reduced clinical disease severity ( as indexed by the Unified Parkinson 's Disease Rating Scale ) and markedly improved reaction times , but did not improve the prolonged P300 latencies in PD patients ( 429 ± 36 ms ) . These results confirm that P300 latencies are prolonged in PD . Significantly , bilateral STN stimulation did not improve this electrophysiological measure of cognitive impairment , even though motor disability was markedly reduced . This suggests that some dopa-responsive features are resistant to STN stimulation , possibly due to involvement of dopaminergic deficits outside the nigrostriatal pathway , which are not influenced by outflow from the STN Abstract . Thirty patients with idiopathic Parkinson 's disease were treated with deep brain stimulation electrode in the subthalamic nucleus . After surgery , the patients ' best mean Unified Parkinson 's Disease Rating Scale ( UPDRS III ) scores ( medictionOFF-stimulatorON versus preoperative medicationOFF ) were 77±14 % at 3 months ( n=20 patients ) and 72±14 % at 12 months follow-up ( n=16 ) . The mean reduction in therapy ( expressed in levodopa dose equivalents in mg ) was 68±25 % at 12 months . Postoperative complications were rare , mostly mild , and reversible . Therapeutic success depends on a multidisciplinary team approach , meticulous patient selection , including patients ' cognitive , psychic , and behavioral status , and patient and family lifestyles CONTEXT This study was part of a large double-blind sham surgery-controlled trial design ed to determine the effectiveness of transplantation of human embryonic dopamine neurons into the brains of persons with advanced Parkinson 's disease . This portion of the study investigated the quality of life ( QOL ) of participants during the 1 year of double-blind follow-up . OBJECTIVES To determine whether QOL improved more in the transplant group than in the sham surgery group and to investigate outcomes at 1 year based on perceived treatment ( the type of surgery patients thought they received ) . DESIGN Participants were r and omly assigned to receive either the transplant or sham surgery . Reported results are from the 1-year double-blind period . SETTING Participants were recruited from across the United States and Canada . Assessment and surgery were conducted at 2 separate university medical centers . PARTICIPANTS A volunteer sample of 40 persons with idiopathic Parkinson 's disease participated in the transplant ( " parent " ) study , and 30 agreed to participate in the related QOL study : 12 received the transplant and 18 received sham surgery . INTERVENTIONS Interventions in the parent study were transplantation and sham brain surgery . Assessment s of QOL were made at baseline and 4 , 8 , and 12 months after surgery . MAIN OUTCOME MEASURES Comparison of the actual transplant and sham surgery groups and the perceived treatment groups on QOL and medical outcomes . We also investigated change over time . RESULTS There were 2 differences or changes over time in the transplant and sham surgery groups . Based on perceived treatment , or treatment patients thought they received , there were numerous differences and changes over time . In all cases , those who thought they received the transplant reported better scores . Blind ratings by medical staff showed similar results . CONCLUSIONS The placebo effect was very strong in this study , demonstrating the value of placebo-controlled surgical trials OBJECTIVE Deep brain stimulation ( DBS ) of the globus pallidus internus ( GPi ) and subthalamic nucleus ( STN ) has been reported to be effective in alleviating the symptoms of advanced Parkinson 's disease ( PD ) . Although recent studies suggest that STN stimulation may be superior to GPi stimulation , a r and omized , blinded comparison has not been reported . The present study was design ed to provide a preliminary comparison of the safety and efficacy of DBS at either site . METHODS Ten patients with idiopathic PD , L-dopa-induced dyskinesia , and response fluctuations were r and omized to implantation of bilateral GPi or STN stimulators . Neurological condition was assessed preoperatively with patients on and off L-dopa and on DBS at 10 days and 3 , 6 , and 12 months after implantation . Patients and evaluating clinicians were blinded to stimulation site throughout the study period . Complete follow-up data were analyzed for four GPi patients and five STN patients . RESULTS When off-L-dopa , both GPi and STN groups demonstrated a similar response , with approximately 40 % improvement in Unified PD Rating Scale motor scores after 12 months of DBS . Rigidity , tremor , and bradykinesia improved in both groups . In combination with L-dopa , Unified PD Rating Scale motor scores were more improved by GPi stimulation than by STN stimulation . On-L-dopa axial symptoms were clinical ly improved in the GPi but not the STN group . L-Dopa-induced dyskinesia was reduced by DBS at either site , although medication requirement was reduced only in the STN group . There were no serious intraoperative complications among patients in either group . CONCLUSION Pallidal and STN stimulation appears to be safe and efficacious for the management of advanced PD . A larger study is needed to investigate further the differences in symptom response and the interaction of L-dopa with stimulation at either site BACKGROUND Although the short-term benefits of bilateral stimulation of the subthalamic nucleus in patients with advanced Parkinson 's disease have been well documented , the long-term outcomes of the procedure are unknown . METHODS We conducted a five-year prospect i ve study of the first 49 consecutive patients whom we treated with bilateral stimulation of the subthalamic nucleus . Patients were assessed at one , three , and five years with levodopa ( on medication ) and without levodopa ( off medication ) , with use of the Unified Parkinson 's Disease Rating Scale . Seven patients did not complete the study : three died , and four were lost to follow-up . RESULTS As compared with base line , the patients ' scores at five years for motor function while off medication improved by 54 percent ( P<0.001 ) and those for activities of daily living improved by 49 percent ( P<0.001 ) . Speech was the only motor function for which off-medication scores did not improve . The scores for motor function on medication did not improve one year after surgery , except for the dyskinesia scores . On-medication akinesia , speech , postural stability , and freezing of gait worsened between year 1 and year 5 ( P<0.001 for all comparisons ) . At five years , the dose of dopaminergic treatment and the duration and severity of levodopa-induced dyskinesia were reduced , as compared with base line ( P<0.001 for each comparison ) . The average scores for cognitive performance remained un Output:	Bilateral subthalamic nucleus stimulation is effective in the treatment of PD . Further refinements in patient selection and surgical technique may lessen the incidence of complications associated with this procedure
MS2990	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background A commonly reported problem with the conduct of multicentre r and omised controlled trials ( RCTs ) is that recruitment is often slower or more difficult than expected , with many trials failing to reach their planned sample size within the timescale and funding originally envisaged . The aim of this study was to explore factors that may have been associated with good and poor recruitment in a cohort of multicentre trials funded by two public bodies : the UK Medical Research Council ( MRC ) and the Health Technology Assessment ( HTA ) Programme . Methods The cohort of trials was identified from the administrative data bases held by the two funding bodies . 114 trials that recruited participants between 1994 and 2002 met the inclusion criteria . The full scientific applications and subsequent trial reports su bmi tted by the trial teams to the funders provided the principal data sources . Associations between trial characteristics and recruitment success were tested using the Chi-squared test , or Fisher 's exact test where appropriate . Results Less than a third ( 31 % ) of the trials achieved their original recruitment target and half ( 53 % ) were awarded an extension . The proportion achieving targets did not appear to improve over time . The overall start to recruitment was delayed in 47 ( 41 % ) trials and early recruitment problems were identified in 77 ( 63 % ) trials . The inter-relationship between trial features and recruitment success was complex . A variety of strategies were employed to try to increase recruitment , but their success could not be assessed . Conclusion Recruitment problems are complex and challenging . Many of the trials in the cohort experienced recruitment difficulties . Trials often required extended recruitment periods ( sometimes supported by additional funds ) . While this is of continuing concern , success in addressing the trial question may be more important than recruitment alone Objectives : To determine the effects of risk and payment on subjects ’ willingness to participate , and to examine how payment influences subjects ’ potential behaviours and risk evaluations . Methods : A 3 ( level of risk ) × 3 ( level of monetary payment ) , between subjects , completely r and omised factorial design was used . Students enrolled at one of five US pharmacy schools read a recruitment notice and informed consent form for a hypothetical study , and completed a question naire . Risk level was manipulated using recruitment notices and informed consent documents from hypothetical biomedical research projects . Payment levels were determined using the payment models evaluated by Dickert and Grady as a guide . Five dependent variables were assessed in the question naire : willingness to participate , willingness to participate with no payment , propensity to neglect to tell about restricted activities , propensity to neglect to tell about negative effects , and risk rating . Results : Monetary payment had positive effects on respondents ’ willingness to participate in research , regardless of the level of risk . However , higher monetary payments did not appear to blind respondents to the risks of a study . Payment had some influence on respondents ’ potential behaviours regarding concealing information about restricted activities . However , payment did not appear to have a significant effect on respondents ’ propensity to neglect to tell research ers about negative effects . Conclusions : Monetary payments appear to do what they are intended to do : make subjects more willing to participate in research . Concerns about payments blinding subjects to risks could not be substantiated in the present study . However , the findings do raise other concerns — notably the potential for payments to diminish the integrity of a study ’s findings . Future research is critical to make sound decisions about the payment of research subjects Background It is notoriously difficult to recruit patients to r and omised controlled trials in primary care . This is particularly true when the disease process under investigation occurs relatively infrequently and must be investigated during a brief time window . Bell 's palsy , an acute unilateral paralysis of the facial nerve is just such a relatively rare condition . In this case study we describe the organisational issues presented in setting up a large r and omised controlled trial of the management of Bell 's palsy across primary and secondary care in Scotl and and how we managed to successfully recruit and retain patients presenting in the community . Methods Where possible we used existing evidence on recruitment strategies to maximise recruitment and retention . We consider that the key issues in the success of this study were ; the fact that the research was seen as clinical ly important by the clinicians who had initial responsibility for recruitment ; employing an experienced trial co-ordinator and dedicated research ers willing to recruit participants seven days per week and to visit them at home at a time convenient to them , hence reducing missed patients and ensuring they were retained in the study ; national visibility and repeated publicity at a local level delivered by locally based principal investigators well known to their primary care community ; encouraging recruitment by payment to practice s and reducing the workload of the referring doctors by providing immediate access to specialist care ; good collaboration between primary and secondary care and basing local investigators in the otolarnygology trial centres Results Although the recruitment rate did not meet our initial expectations , enhanced retention meant that we exceeded our planned target of recruiting 550 patients within the planned time-scale . Conclusion While difficult , recruitment to and retention within multi-centre trials from primary care can be successfully achieved through the application of the best available evidence , establishing good relationships with practice s , minimising the workload of those involved in recruitment and offering enhanced care to all participants . Primary care trialists should describe their experiences of the methods used to persuade patients to participate in their trials when publishing their results OBJECTIVES To evaluate the impact of an information booklet on HIV clinical trials , Clinical Trials in HIV and AIDS : Information For People Who Are Thinking About Joining a Trial , in addition to the st and ard trial information ( SI ) on patients ' knowledge ; underst and ing and attitudes about clinical trials ; and to investigate patients ' motivations and reasons for enrolling or not enrolling in a clinical trial . METHODS Fifty HIV-1 positive patients who attended the HIV clinic at a west London hospital were r and omized to receive either SI alone ( n = 27 ) or SI and a 16 page information booklet explaining the principles and procedures of HIV clinical trials ( n = 23 ) . A self-administered question naire was used at baseline to assess past experience and attitudes to clinical trials ( 10 questions ) , knowledge and underst and ing of HIV treatments ( 8 questions ) and clinical trials ( 11 questions ) . At 2 - 6 months after r and omization , a second interviewer-administered question naire addressed the patient 's assessment of the usefulness and comprehensiveness of the information provided by the SI and information booklet , whether or not the patient had enrolled in a clinical trial and reasons for enrolling/not enrolling , knowledge of specific aspects of the trial protocol the patient was eligible to join ( 13 questions ) and general knowledge of clinical trial procedures ( repeat of 11 baseline questions ) . Changes in the attitudes and scores on knowledge and underst and ing of clinical trials were compared for the two groups . RESULTS In both groups , patient knowledge of clinical trial procedures improved significantly over the study period . The median score increased from 30 at baseline to 35/44 at follow-up ( SI only ) vs. 24 - 31/44 ( SI plus booklet ) , but this did not differ significantly between the two groups . However , knowledge of the specific trial protocol was poor [ median score 13/25 , interquartile range ( IQR ) 8 - 14 ] , and there was no difference in the scores for the two groups . The prime motivations for joining a clinical trial were to benefit personal health and to gain access to new treatments . Potential side-effects were the main concern of prospect i ve trial participants . CONCLUSIONS This small trial shows that , while the patients ' general knowledge and underst and ing of clinical trials improved over time , this was not improved by the information booklet and re collection of the details of the relevant trial protocol remained poor Background Recruitment is a major challenge for trials but there is little evidence regarding interventions to increase trial recruitment . We report three controlled trials of interventions to increase recruitment to the Txt2stop trial . Purpose To evaluate : Trial 1 . The impact on registration s of a text message regarding an online registration facility ; Trial 2 . The impact on r and omizations of sending £ 5 with a covering letter to those eligible to join the trial ; Trial 3 . The impact on r and omizations of text messages containing quotes from existing participants . Methods Single blind controlled trials with allocation concealment . Interventions : Trial 1 : A text message regarding our new online registration facility ; Trial 2 : A letter with £ 5 enclosed ; Trial 3 : A series of four text messages containing quotes from participants . The control group in each trial received st and ard Txt2stop procedures . Results Trial 1 : 3.6 % ( 17/470 ) of the intervention group and 1.1 % ( 5/467 ) of the control group registered for the trial , risk difference 2.5 % ( 95 % CI 0.6—4.5 ) . 0 % ( 0/ 470 ) of the intervention group and 0.2 % ( 1/467 ) of the control group registered successfully online , risk difference —0.2 ( 95 % CI —0.6—0.2 ) ; Trial 2 : 4.5 % ( 11/246 ) of the intervention group and 0.4 % ( 1/245 ) of the control group were r and omized into the Txt2stop trial , risk difference 4.0 % ( 95 % CI 1.4—6.7 ) ; Trial 3 : 3.5 % ( 14/405 ) of the intervention group and 0 % ( 0/406 ) of the control group were r and omized into the Txt2stop trial , risk difference 3.5 ( 95 % CI 1.7—5.2 ) . Limitations There were no baseline data available for trial 1 . Allocation of participant IDs in trials 2 and 3 were systematic . Conclusion Sending a text message about an online registration facility increased registration s to Txt2stop , but did not increase online registration s. Sending a £ 5 reimbursement for participants ’ time and sending text messages containing quotes from existing participants increased r and omizations into the Txt2stop trial . Clinical Trials 2010 ; 7 : 265—273 . BACKGROUND physical activity studies in older people often have poor recruitment . Including a question naire with the invitation would provide information about non- participants and selection bias , but could reduce recruitment . Telephone contact might encourage participation . OBJECTIVE to test the effects of different strategies for recruitment into a study of physical activity in older people . DESIGN factorial r and omised controlled trial . R and omisation by household into four groups : telephone contact plus question naire , telephone contact only , question naire only , neither . SETTING primary care , Oxfordshire , United Kingdom . PARTICIPANTS 560 patients > or = 65 years r and omly selected after exclusions . INTERVENTIONS question naire to assess health , functional ability and physical activity . Telephone contact by the research nurse a week after sending study information . MAIN OUTCOME MEASURE recruitment into physical activity study . RESULTS telephone contact increased recruitment : contact 47.9 % ( 134/280 ) , no contact 37.9 % ( 106/280 ) , difference ( adjusted for the clustering effect of household ) 10.0 % ( 95 % CI 0.2 - 19.8 ) . Question naire inclusion did not significantly reduce recruitment : no question naire 44.3 % ( 124/280 ) question naire 41.4 % ( 116/280 ) difference -2.9 % ( 95 % CI -12.7 - 7.0 ) . CONCLUSIONS telephone contact significantly increased recruitment and should be considered in studies where recruitment may be low . While inclusion of a question naire provided valuable information on non- participants and did not significantly reduce recruitment , an adverse recruitment effect could not be excluded BACKGROUND Latinas have low rates of participation in breast cancer prevention trials . We evaluated the feasibility and effectiveness of a r and omized trial of brief counseling and print material s compared to print material s alone to increase intent to participate in a breast cancer prevention trial . METHODS We enrolled 450 women Spanish-speaking women from three urban community primary care clinics . The outcome was intent , defined as might , probably , or definitely would enroll in the trial . We also examined results using a more stringent definition restricted to probably and definitely intend to participate . RESULTS The trial was feasible within these busy clinics , and 96 % of women agreed to participate . The level of breast cancer knowledge was fairly high ( 66 % correct answers ) , but underst and ing about clinical trials was lower ( 40.5 % correct answers ) . Using the less stringent criteria for intent , 72 % of women stated that they intended to enroll in the STAR trial if eligible , but rates of intent decreased to 52 % with framing that included medication side effects and 45 % if uterine cancer was mentioned ( P < 0.01 for trend ) . Using the more stringent definition , slightly fewer than half of the women indicated an interest in participating , with the same trend towards decreasing intent with increasing presentation of side effects . The intervention was only effective using the less stringent definition and if no side effects were mentioned ( 77 % intent vs. 67 % in the intervention and control groups , respectively , P = 0.03 ) . Intention was independently associated with greater worry about breast cancer and younger age , but not acculturation or knowledge . CONCLUSIONS Latina women are interested in participating in clinical trials to prevent breast cancer , although interest declines with increasing discussion of side effects . Unfortunately , brief education only increased rates of intention using the least stringent definition and when no side effects were presented in framing the question . Future work should focus on qualitative research to underst and the theoretical foundations of preventive health behaviors in this population PURPOSE Studies have documented that the majority of consent documents for medical diagnosis and treatment are written at a reading level above that of the majority of the U.S. population . This study hypothesized that use of an easy-to-read consent statement , when compared with a st and ard consent statement , will result in higher patient comprehension of the clinical treatment protocol , lower patient anx Output:	However , the effect of many other strategies is less clear , including the use of video to provide trial information and interventions aim ed at recruiters . Questions remain as to the applicability of results originating from hypothetical trials , including those relating to the use of monetary incentives , and there is a clear knowledge gap with regard to effective strategies aim ed at recruiters
MS2991	*TASK* the task is to summarize an input biomedical literature in six sentences *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 use of colchicine to prevent acute gout flares during initiation of allopurinol therapy is widely practice d despite lack of proven benefit . We investigated if colchicine administration during initiation of allopurinol for chronic gouty arthritis reduces the frequency and /or severity of acute gout flares . METHODS Patients starting allopurinol for crystal-proven chronic gouty arthritis were r and omized to receive colchicine 0.6 mg po bid or placebo in a r and omized , prospect i ve , double blind , placebo controlled trial . Subjects were followed for evidence of acute gout flares and remained on study drug for 3 months beyond attaining a serum urate concentration < 6.5 mg/dl . Treatment arms were analyzed regarding frequency of flares , likelihood of any flare or multiple flares , severity of flares on the visual analog scale ( VAS ) , and length of flares in days . RESULTS Forty-three subjects were studied . Subjects treated with colchicine experienced fewer total flares ( 0.52 vs 2.91 , p = 0.008 ) , fewer flares from 0 to 3 months ( 0.57 vs 1.91 , p = 0.022 ) , fewer flares 3 - 6 months ( 0 vs 1.05 , p = 0.033 ) , less severe flares as reported on VAS ( 3.64 vs 5.08 , p = 0.018 ) , and fewer recurrent gout flares ( p = 0.001 ) . Colchicine was well tolerated . CONCLUSION Colchicine prophylaxis during initiation of allopurinol for chronic gouty arthritis reduces the frequency and severity of acute flares , and reduces the likelihood of recurrent flares . Treating patients with colchicine during initiation of allopurinol therapy for 6 months is supported by our data Background — Although gout and hyperuricemia are related to several conditions that are associated with reduced survival , no prospect i ve data are available on the independent impact of gout on mortality . Furthermore , although many studies have suggested that hyperuricemia is associated with cardiovascular disease ( CVD ) , limited data are available on the impact of gout on CVD . Methods and Results — Over a 12-year period , we prospect ively examined the relation between a history of gout and the risk of death and myocardial infa rct ion in 51 297 male participants of the Health Professionals Follow-Up Study . During the 12 years of follow-up , we documented 5825 deaths from all causes , which included 2132 deaths from CVD and 1576 deaths from coronary heart disease ( CHD ) . Compared with men without history of gout and CHD at baseline , the multivariate relative risks among men with history of gout were 1.28 ( 95 % confidence interval [ CI ] , 1.15 to 1.41 ) for total mortality , 1.38 ( 95 % CI , 1.15 to 1.66 ) for CVD deaths , and 1.55 ( 95 % CI , 1.24 to 1.93 ) for fatal CHD . The corresponding relative risks among men with preexisting CHD were 1.25 ( 95 % CI , 1.09 to 1.45 ) , 1.26 ( 95 % CI , 1.07 to 1.50 ) , and 1.24 ( 95 % CI , 1.04 to 1.49 ) , respectively . In addition , men with gout had a higher risk of nonfatal myocardial infa rct ion than men without gout ( multivariate relative risk , 1.59 ; 95 % CI , 1.04 to 2.41 ) . Conclusions — These prospect i ve data indicate that men with gout have a higher risk of death from all causes . Among men without preexisting CHD , the increased mortality risk is primarily a result of an elevated risk of CVD death , particularly from CHD Objectives : To investigate the efficacy and tolerability of allopurinol as the first-choice antihyperuricaemic treatment for gout , and compare the efficacy and tolerability of benzbromarone and probenecid as second-choice treatment . Methods : Prospect i ve , multicentre , open-label , two-stage r and omised controlled trial in gout patients with normal renal function . Enrolled patients were given 300 mg allopurinol for 2 months ( stage 1 ) . Those patients who could not tolerate allopurinol or who did not attain the target serum urate concentration ( sUr ) ⩽0.30 mmol/l ( 5.0 mg/dl ) , which was defined as successful , were r and omised to benzbromarone 200 mg/day or probenecid 2 g/day for another 2 months ( stage 2 ) . Results : 96 patients were enrolled in stage 1 . 82 patients ( 85 % ) were eligible for the analysis at the end of stage 1 : there was a mean ( SD ) decrease in sUr concentration of 35 (11)% from baseline ; 20 patients ( 24 % ) attained target sUr ⩽0.30 mmol/l ; and 9 patients ( 11 % ) stopped allopurinol because of adverse drug reactions . 62 patients were enrolled in stage 2 . 27 patients received benzbromarone ( 3 patients not eligible for analysis ) and 35 received probenecid ( 4 patients not eligible for analysis ) . Treatment with benzbromarone was successful in 22/24 patients ( 92 % ) and with probenecid in 20/31 patients ( 65 % ) ( p = 0.03 compared with benzbromarone ) . Compared with baseline values , there was a mean ( SD ) decrease of sUr concentration of 64 (9)% with benzbromarone and 50 (7)% with probenecid ( p<0.001 ) . Conclusion : This study showed that allopurinol 300 mg/day has a poor efficacy and tolerability profile when used to attain a biochemical predefined target level of sUr ⩽0.30 mmol/l , following 2 months of treatment . In stage 2 , benzbromarone 200 mg/day was more effective and better tolerated than probenecid 2 g/day . Trial registration number : IS RCT N21473387 Aim Assess influences of demographics and co-morbidities of gout patients with or without diabetes on safety and efficacy of urate-lowering agents . Methods Post-hoc analysis of 312 diabetic and 1957 non-diabetic gout patients [ baseline serum urate levels ( sUA ) ≥8.0 mg/dl ] enrolled in a 6-month r and omized controlled trial comparing urate-lowering efficacy ( ULE ) and safety of daily xanthine oxidase inhibitors ( XOIs ) febuxostat ( 40 mg or 80 mg ) and allopurinol ( 200 mg or 300 mg ) . We compared baseline demographic , gout and co-morbid characteristics , ULE , and safety of XOI treatment in diabetic and non-diabetic gout patients . ULE was measured by the proportion of diabetic and non-diabetic patients in each treatment group achieving final visit sUA < 6.0 mg/dl . Safety was monitored throughout the trial . Results Diabetic gout patients were older , more frequently female , and had longer gout duration . Co-morbidities were more frequent among diabetic patients : cardiovascular disease ; impaired renal function ; hyperlipidemia ; and obesity ( body mass index > 30 kg/m2 ) ( p < 0.001 for all comparisons ) . Febuxostat 80 mg ULE exceeded that of febuxostat 40 mg or allopurinol ( p < 0.050 ) at all levels of renal function , achieving sUA goal range in the majority of diabetic and non-diabetic patients . Diabetics and non-diabetics reported self-limiting diarrhoea and URIs as the most common adverse events . Conclusions Despite higher co-morbidity rates in diabetic patients , febuxostat and allopurinol were safe in both groups at the doses tested . Febuxostat 80 mg achieved sUA < 6.0 mg/dl more often than febuxostat 40 mg or allopurinol at commonly prescribed doses Introduction The purpose of this study was to compare urate-lowering ( UL ) efficacy and safety of daily febuxostat and allopurinol in subjects with gout and serum urate ( sUA ) ≥ 8.0 mg/dL in a six-month trial . Methods Subjects ( n = 2,269 ) were r and omized to febuxostat 40 mg or 80 mg , or allopurinol 300 mg ( 200 mg in moderate renal impairment ) . Endpoints included the proportion of all subjects with sUA < 6.0 mg/dL and the proportion of subjects with mild/moderate renal impairment and sUA < 6.0 mg/dL. Safety assessment s included blinded adjudication of each cardiovascular ( CV ) adverse event ( AE ) and death . Results Comorbidities included : renal impairment ( 65 % ) ; obesity ( 64 % ) ; hyperlipidemia ( 42 % ) ; and hypertension ( 53 % ) . In febuxostat 40 mg , febuxostat 80 mg , and allopurinol groups , primary endpoint was achieved in 45 % , 67 % , and 42 % , respectively . Febuxostat 40 mg UL was statistically non-inferior to allopurinol , but febuxostat 80 mg was superior to both ( P < 0.001 ) . Achievement of target sUA in subjects with renal impairment was also superior with febuxostat 80 mg ( 72 % ; P < 0.001 ) compared with febuxostat 40 mg ( 50 % ) or allopurinol ( 42 % ) , but febuxostat 40 mg showed greater efficacy than allopurinol ( P = 0.021 ) . Rates of AEs did not differ across treatment groups . Adjudicated ( APTC ) CV event rates were 0.0 % for febuxostat 40 mg and 0.4 % for both febuxostat 80 mg and allopurinol . One death occurred in each febuxostat group and three in the allopurinol group . Conclusions Urate-lowering efficacy of febuxostat 80 mg exceeded that of febuxostat 40 mg and allopurinol ( 300/200 mg ) , which were comparable . In subjects with mild/moderate renal impairment , both febuxostat doses were more efficacious than allopurinol and equally safe . At the doses tested , safety of febuxostat and allopurinol was comparable . Clinical Trial Registration Introduction Gout affects 2.5 % of the UK 's adult population and is now the most common type of inflammatory arthritis . The long-term management of gout requires reduction of serum urate levels and this is most often achieved with use of xanthine oxidase inhibitors , such as allopurinol . Febuxostat is the first new xanthine oxidase inhibitor since allopurinol and was licensed for use in 2008 . The European Medicines Agency requested a postlicensing cardiovascular safety study of febuxostat versus allopurinol , which has been named the Febuxostat versus Allopurinol Streamlined trial ( FAST ) . Methods and analysis FAST is a cardiovascular safety study using the prospect i ve , r and omised , open , blinded endpoint design . FAST is recruiting in the UK and Denmark . Recruited patients are aged over 60 years , prescribed allopurinol for symptomatic hyperuricaemia and have at least one additional cardiovascular risk factor . After an allopurinol lead-in phase where the dose of allopurinol is optimised to achieve European League against Rheumatism ( EULAR ) urate targets ( serum urate < 357 µmol/L ) , patients are r and omised to either continue optimal dose allopurinol or to use febuxostat . Patients are followed-up for an average of 3 years . The primary endpoint is first occurrence of the Anti-Platelet Trialists ’ Collaboration ( APTC ) cardiovascular endpoint of non-fatal myocardial infa rct ion , non-fatal stroke or cardiovascular death . Secondary endpoints are all cause mortality and hospitalisations for heart failure , unstable , new or worsening angina , coronary or cerebral revascularisation , transient ischaemic attack , non-fatal cardiac arrest , venous and peripheral arterial vascular thrombotic event and arrhythmia with no evidence of ischaemia . The primary analysis is a non-inferiority analysis with a non-inferiority upper limit for the HR for the primary outcome of 1.3 . Ethics and dissemination FAST ( IS RCT N72443728 ) has ethical approval in the UK and Denmark , and results will be published in a peer review ed journal . Trial Registration number FAST is registered in the EU Clinical Trials Register ( EUDRACT No : 201 Output:	CV events did not decrease over time . Comparing shorter studies ( < 52 weeks ) to longer ones did not reveal any statistical differences . However , in long-term studies with febuxostat vs allopurinol , results were nearly significant , with more CVE occurring with febuxostat treatment . Conclusion RCT data do not suggest differences in CV events among ULTs in gout . Trials had few events despite high-risk patients being enrolled and may have been too short to show CV reduction by controlling inflammatory attacks and lowering uric acid
MS2992	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Femoroacetabular impingement is a common hip pathology result ing in pain and impaired physical function . However , very little is known about gait differences between those with and without femoroacetabular impingement . Thus , the purpose of this study was to compare three-dimensional gait kinematics and kinetics between those with femoroacetabular impingement and a healthy , pain-free control group . METHODS Three-dimensional gait analysis was conducted on 30 individuals with symptomatic femoroacetabular impingement scheduled for surgery and 30 pain-free controls . Spatiotemporal and peak hip kinematics and joint moments were compared between the two groups . Ensemble averages were also calculated for kinematic and kinetic profiles across the gait cycle in all three planes of movement for visual inspection . FINDINGS Participants with femoroacetabular impingement walked slower and with significantly smaller cadences than those in the control group . Kinematically , the impingement group exhibited significantly less peak hip extension , adduction and internal rotation during stance , with effect sizes ranging from 0.48 ( adduction ) to 1.00 ( internal rotation ) . Finally , those with FAI exhibited significantly less peak external hip flexion ( effect size=0.52 ) and external rotation ( effect size=0.85 ) moments than the control group . INTERPRETATION Individuals with femoroacetabular impingement exhibit differences in gait kinematics in all planes of motion compared to those with without FAI . These findings support the need for focused neuromuscular reconditioning across all movement directions in this patient group OBJECTIVE To determine if compensatory actions take place at the pelvis and other joints of the affected lower limb in subjects who were in an early stage of hip osteoarthritis ( OA ) . DESIGN Nonr and omized , case-control study . SETTING A gait laboratory . PARTICIPANTS Seventeen patients with OA of the hip ( clinical group ) matched with 17 healthy elderly subjects ( non clinical group ) . INTERVENTIONS Video data obtained while subjects walked a 10-meter walkway twice and stepped across a forceplate . MAIN OUTCOME MEASURES Four phasic and temporal gait parameters ( walking speed , stance phase relative duration , stride length , cadence ) 10 pelvic ( pelvic tilt , obliquity , rotation at push-off maximum range of motion for all 3 ) and hip ( 3 hip angles at push-off , maximum hip flexion ) kinematic parameters , 3 hip moments , and twenty-seven 3-dimensional peak muscle powers ( labeled by joint , peak power , plane ) developed in the lower limb joints during the gait cycle . RESULTS Subjects in the clinical group were characterized by a 12.4 % slower walking speed . The pelvis was more upwardly tilted ( 2.5 times ) at push-off in the clinical group than in the non clinical group . Obliquity , measured in the frontal plane , revealed that the pelvis dropped more ( 2.4 times ) on the unsupported limb of the clinical group at push-off . In the sagittal plane , subjects in the clinical group absorbed less energy in their second hip peak power for decelerating the thigh extension and generated less hip pull ( third hip peak power ) than the non clinical group by 34 % and 29 % , respectively . In the sagittal plane , the clinical group had 57 % lower second knee peak power to straighten the joint shortly after heel strike , and 43 % less knee absorption ( third peak power ) at push-off . During the push-off phase , the clinical group developed more than twice their third peak knee power in the frontal plane and 5 times more their third peak knee power in the transversal plane than the peak knee power of the non clinical group in an attempt to control knee adduction and to facilitate body-weight transfer by an internal rotation . At the end of the swing phase , the fourth peak power in the sagittal plane showed the absorption power required to decelerate the leg ; it was reduced by 35 % in the clinical group , representing a strategy to increase walking speed by lengthening the stride length . CONCLUSIONS Even at an early stage of hip OA , joint degeneration was compensated by an increase in pelvis motion and muscle power generation or absorption modifications in other lower limb joints Objective To determine the association between cam impingement , which is hip incongruity by a non-spherical femoral head and development of osteoarthritis . Methods A nationwide prospect i ve cohort study of 1002 early symptomatic osteoarthritis patients ( CHECK ) , of which st and ardised anteroposterior pelvic radiographs were obtained at baseline and at 2 and 5 years follow-up . Asphericity of the femoral head was measured by the α angle . Clinical ly , decreased internal hip rotation ( ≤20 ° ) is suggestive of cam impingement . The strength of association between those parameters at baseline and development of incident osteoarthritis ( K&L grade 2 ) or end-stage osteoarthritis ( K&L grade s 3 , 4 , or total hip replacement ) within 5 years was expressed in OR using generalised estimating equations . Results At baseline , 76 % of the included hips had no radiographic signs of osteoarthritis and 24 % doubtful osteoarthritis . Within 5 years , 2.76 % developed end-stage osteoarthritis . A moderate ( α angle > 60 ° ) and severe ( α angle > 83 ° ) cam-type deformity result ed in adjusted OR of 3.67 ( 95 % CI 1.68 to 8.01 ) and 9.66 ( 95 % CI 4.72 to 19.78 ) , respectively , for end-stage osteoarthritis . The combination of severe cam-type deformity and decreased internal rotation at baseline result ed in an even more pronounced adjusted OR , and in a positive predictive value of 52.6 % for end-stage osteoarthritis . For incident osteoarthritis , only a moderate cam-type deformity was predictive OR=2.42 ( 95 % CI 1.15 to 5.06 ) . Conclusions Individuals with both severe cam-type deformity and reduced internal rotation are strongly predisposed to fast progression to end-stage osteoarthritis . As cam impingement might be a modifiable risk factor , early recognition of this condition is important Gluteus minimus is believed to consist of two structurally and functionally unique segments ( anterior and posterior ) ; however there is a lack of electromyography ( EMG ) research that attempts to verify current theoretical knowledge of this muscle . The purpose of this study was therefore to evaluate the function of gluteus minimus during gait , and to determine whether anterior and posterior segments are functionally independent . Bipolar fine wire intramuscular EMG electrodes were inserted into anterior and posterior gluteus minimus segments of fifteen healthy volunteers ( 9 males ) according to previously verified guidelines . Participants completed a series of four walking trials , followed by maximum voluntary isometric contractions in five different positions . Temporal and amplitude variables for each segment were compared across the gait cycle with independent t-tests . The relative contribution of each segment to the maximum resisted trials was compared with Mann-Whitney U tests ( α = 0.05 ) . Anterior and posterior segments were contracting at different relative intensities for three of the five maximum resisted trials ( effect size = 0.39 to 0.62 , P < 0.037 ) . The posterior segment was larger in EMG amplitude ( peak and average ) during the first 20 % of the gait cycle ( effect size = 0.96 to 1.03 , P < 0.02 ) , while the anterior segment peaked later in the stance phase ( effect size = 0.83 , P = 0.034 ) . Gluteus minimus is therefore composed of functionally independent segments . These results build on contemporary theoretical knowledge and may signify hip stabilising roles for each segment across different phases of the gait cycle OBJECTIVE To investigate the differences in hip movement patterns during different daily and athletic activities in persons with cam-type femoroacetabular impingement ( FAI ) with and without cartilage lesions compared with control subjects in a preliminary study . DESIGN Controlled laboratory study using a cross-sectional design . SETTING Research institution with a tertiary care medical center . PARTICIPANTS Fifteen subjects [ M : F , 13:2 ; age , 31.6 ± 9.7 years ( range , 22 - 52 years ) ; body mass index , 24.9 ± 4.6 ( range , 18.8 - 38.4 ) ; FAI : control , 7:8 ] . METHODS All subjects had 3-Tesla magnetic resonance imaging of the hip and also underwent 3-dimensional motion capture during walking , deep-squat , and drop-l and ing tasks . Experienced radiologists grade d cartilage lesions on clinical magnetic resonance images . OUTCOMES Peak kinematic and kinetic variables were compared between subjects who did and did not have FAI , and subjects who had FAI and cartilage lesions were compared with subjects who did not have cartilage lesions . RESULTS Subjects who had FAI demonstrated no significant differences for walking or drop l and ing compared with control subjects . However , during the deep-squat task , subjects with FAI adducted more and had a greater internal rotation moment . Subjects who had cartilage lesions in the presence of a cam lesion demonstrated ( 1 ) no difference for walking ; ( 2 ) greater adduction , greater internal rotation moment , and lower transverse plane range of motion during the deep-squat task ; and ( 3 ) greater adduction and lower internal rotation during the drop-l and ing task compared with subjects who did not have cartilage lesions . CONCLUSIONS We observed differences in movement patterns between subjects who had FAI compared with control subjects . However , the differences were more pronounced between subjects with FAI who had cartilage lesions compared with subjects who did not have cartilage lesions . These findings highlight the importance of underst and ing the complex interplay between bony morphologic features , cartilage lesions , and movement patterns in persons with cam-type FAI Output:	Conclusion This review suggests that patients with FAIS may demonstrate hip biomechanical impairments during walking and squatting , with minimal literature available to comment on other tasks . Clinical relevance The information presented in the review provides insight into the biomechanical differences associated with FAIS ; however , the between-group differences were small to moderate .
MS2993	*TASK* the task is to summarize an input biomedical literature in six sentences *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 : Interleukin-10 ( IL-10 ) is an anti-inflammatory cytokine that suppresses lymphocyte functions , regulates production of proinflammatory cytokines , and suppresses nitric oxide production by activated macrophages . We examined IL-10 expression and its value as a surrogate index for nitric oxide ( NO ) production in endothelial cultures obtained from saphenous vein sample s. Methods : Using 2 different techniques ( the open and endoscopic ) , we harvested sample s of human saphenous veins from 90 r and omly selected patients undergoing coronary artery bypass surgery ( CABG ) . Endothelial cells collected from the vein sample s retrieved through both techniques were cultured for 72 hours . Using a solid phase enzyme linked-immuno-sorbent assay ( ELISA ) , we analyzed pre- and postoperative sera , in addition to the supernatants from the cultures , for IL-10 . Results : Mean preoperative levels of IL-10 ( 0.09 ± 0.04 pg/mL ) did not differ significantly from that for postoperative sera ( 0.14 ± 0.17 pg/mL ) ( P = 0.54 ) . Mean IL-10 levels for endothelial cell culture supernatants did not differ significantly between the endoscopic ( 0.32 ± 0.39 pg/mL ) and the open method ( 0.46 ± 0.80 pg/mL ) ( P = 0.30 ) . Conclusion : Our findings indicate that endoscopic and open saphenectomies are technically comparable with respect to their effects on IL-10 release during saphenous vein harvesting for CABG . We recommend the endoscopic method for its low morbidity and earlier hospital discharge BACKGROUND Levels of the cytokines Interleukin-1 ( IL-1 ) , IL-2 , and IL-10 are sensitive to the traumatic effect of saphenous vein harvesting . Their levels are compared between the endoscopic and traditional open techniques of harvesting . METHODS Sample s of human saphenous veins were harvested from 90 r and omly selected patients undergoing coronary artery bypass surgery ( CABG ) , using the open or endoscopic techniques . Endothelial cells collected from the vein sample s retrieved through both techniques were cultured for 72 hours . Pre and postoperative sera , in addition to the supernatants from the cultures , were analyzed for IL-1 , IL-2 , and IL-10 using ELISA . RESULTS Mean preoperative concentrations of IL-1 , Il-2 , and IL-10 were 0.11+/- 0.04 , 0.09 + /- 0.04 , and 0.09 + /- 0.04 pg/ml , respectively . Corresponding values for postoperative sera were 0.13 + /- 0.08 , 0.12 + /- 0.10 , 0.14 + /- 0.17 pg/ml , respectively . The differences between pre and postoperative means for each cytokine were not statistically significant ( p = 0.13 , 0.18 , 0.05 , respectively ) . Mean IL-1 , IL-2 , and IL-10 concentrations for endothelial cell culture supernatants did not differ significantly between the endoscopic ( 0.17 + /- 0.11 , 0.11 + /- 0.05 , and 0.32 + /- 0.40 pg/ml , respectively ) and the open method ( 0.19 + /- 0.16 , 0.11 + /- 0.05 , and 0.46 + /- 0.80 pg/ml , respectively ) ( p = 0.48 , 0.81 , 0.30 , respectively ) . CONCLUSION Since endoscopic and open saphenectomies are technically comparable with respect to their effects on IL-1 , Il-2 , and IL-10 levels , we recommend the endoscopic method for its lower morbidity and the potential for earlier hospital discharge OBJECTIVE Preparation of the great saphenous vein for coronary artery bypass grafts is usually performed through one or many cutaneous incisions . A technique of endoscopic harvesting is now available . An aim of the study was to compare both methods , prospect ively . METHODS Sixty coronary artery bypass grafting patients were r and omly assigned to two groups according to saphenous vein harvesting technique : 30 patients to group 1 -- open harvesting technique ( OHT ) and 30 patients to group 2 -- endoscopic harvesting technique ( EHT ) . The results were assessed on the basis of ( 1 ) clinical outcome ( hematomas , inflammations ) , ( 2 ) length of the cutaneous incisions compared to length of the segment of vein harvested , ( 3 ) time of harvesting , ( 4 ) postoperative pain . RESULTS Both groups were comparable in terms of : age , sex , diabetes , peripheral artery disease , site of harvesting , number of anastomoses , and length of the vein harvested . Both the length of the cutaneous incisions and the postoperative pain were decreased in the EHT group . Harvesting time was increased in the OHT group . CONCLUSIONS Endoscopic saphenous vein harvesting allows improved aesthetic aspect , less postoperative discomfort , with an increased time in harvesting in the beginning BACKGROUND Minimally invasive techniques to harvest the saphenous vein for coronary artery bypass grafting continue to improve and evolve . Smaller cutaneous incisions have been shown to decrease postoperative discomfort and improve healing . We describe a technique involving carbon dioxide insufflation and endoscopic dissection to allow easier and atraumatic dissection . METHODS The VasoView endoscope system ( Origin Medsystems , Inc ) was used to harvest the saphenous vein for coronary artery bypass grafting in 27 patients . This group was compared with 24 patients having traditional saphenous vein harvesting . Wounds were examined for complications daily . Pain and postoperative mobility were quantified independently by physical therapists . RESULTS Comparison of patients in the two groups revealed greater edema in the legs with traditional harvesting . Patients with endoscopic removal also had less pain and increased mobility postoperatively . On average , minimally invasive harvesting allowed patients to ambulate to a predischarge goal of 300 ft 2 days earlier . CONCLUSIONS Minimally invasive harvesting of the saphenous vein by insufflation techniques is safe , effective , and atraumatic to the conduit . Discomfort is minimized , promoting earlier and improved ambulation Background In coronary artery bypass grafting surgery , arterial conduits are preferred because of more favourable long-term patency and outcome . Anyway the greater saphenous vein continues to be the most commonly used bypass conduit . Minimally invasive endoscopic saphenous vein harvesting is increasingly being investigated in order to reduce the morbidity associated with conventional open vein harvesting , includes postoperative leg wound complications , pain and patient satisfaction . However , to date the short and the long-term benefits of the endoscopic technique remain controversial . This study provides an interesting opportunity to address this gap in the literature . Methods / Design Endoscopic Saphenous harvesting with an Open CO2System trial includes two parallel vein harvesting arms in coronary artery bypass grafting surgery . It is an interventional , single centre , prospect i ve , r and omized , safety/efficacy , cost/effectiveness study , in adult patients with elective planned and first isolated coronary artery disease . A simple size of 100 patients for each arm will be required to achieve 80 % statistical power , with a significant level of 0.05 , for detecting most of the formulated hypotheses . A six-weeks leg wound complications rate was assumed to be 20 % in the conventional arm and less of 4 % in the endoscopic arm . Previously quoted studies suggest a first-year vein-graft failure rate of about 20 % with an annual occlusion rate of 1 % to 2 % in the first six years , with practically no difference between the endoscopic and conventional approaches . Similarly , the results on event-free survival rates for the two arms have barely a 2 - 3 % gap . Assuming a 10 % drop-out rate and a 5 % cross-over rate , the goal is to enrol 230 patients from a single Italian cardiac surgery centre . Discussion The goal of this prospect i ve r and omized trial is to compare and to test improvement in wound healing , quality of life , safety/efficacy , cost-effectiveness , short and long-term outcomes and vein-graft patency after endoscopic open CO2 harvesting system versus conventional vein harvesting . The expected results are of high clinical relevance and will show the safety/efficacy or non-inferiority of one treatment approach in terms of vein harvesting for coronary artery bypass grafting surgery . Trial registration www . clinical Trials.gov NCT01121341 UNLABELLED Conventional conduit harvesting used for coronary artery bypass graft for many decades but there has been some wound complication problem . Endoscopic conduit harvesting is a minimal invasive surgery for reduced wounds complication . The authors aim ed to compare the result between two techniques . MATERIAL AND METHOD Prospect i ve enroll of 100 patients for elective coronary artery bypass graft surgery . Divided in 2 groups . The first groups was a convention conduit harvesting ( C groups ) and the second groups was endoscopic conduit harvesting ( E groups ) . The endoscopic conduit harvesting performed using the Maquet Vasoview system under CO2 inflation assisted . RESULTS Endoscopic conduit harvesting was successful 94 % . Harvest time C group 32.4 mins E group 48.9 mins , ET CO2 C group 40.3 , E group 50.9 , Wounds infection C group 6 % E group O , wounds echymosis C group 6 % E group 44 % . CONCLUSION Endoscopic conduit harvesting showed better results with conventional conduit harvesting in wounds with serious complications but they need more harvest time and risk of CO2 embolism . However a long term graft patency needs more investigation Classical excision of saphenous vein grafts requires a continuous incision on the leg or the thigh or both . To minimise the trauma due to this method , an endoscopic method has been recently developed . The aim of this paper was to assess the benefits of this new method compared with the classical technique . One hundred and twenty patients requiring aorto-coronary grafts were included in this prospect i ve study and divided into two groups according to the method of saphenous vein harvesting . Group A comprised 60 patients who underwent the classical method os saphenous vein harvesting and Group B 60 patients who benefited from the endoscopic method . No difference was observed between the two groups with respect to mean age , sex ratio , history of diabetes and obliterative arterial disease of the lower limbs . Parsonnet index number of bypass grafts and length of vein excised . The length of the skin wound in group A was 30.8 + /- 8.5 cm compared with only 4.1 + /- 1 cm in Group B ( p = 0.006 ) but the harvesting time was longer by endoscopy ( 55.7 + /- 23.7 minutes : 72.5 + /- 22.6 minutes for the first 10 patients , 48.5 + /- 24.7 minutes for the last 50 patients ) compared with the classical technique ( 39.8 + /- 6.6 minutes : p = 0.001 ) . Moreover , patients who underwent videosurgery had less operative pain ( 8 % versus 15 % ) ( p = 0.001 ) . The number of infectious complications was slightly lower in Group B ( 3.3 % , 2/60 , versus 10 % , 6/60 ) , ( NS ) . The authors conclude that harvesting of the saphenous vein by videosurgery reduces postoperative pain and gives a more aesthetic result but with a slightly longer operative time at the beginning of the experience Background Saphenous vein remains the most common conduit for coronary artery bypass grafting with increasing uptake of minimally invasive harvesting techniques . While Endoscopic Vein Harvest ( EVH ) has been demonstrated to improve early morbidity compared to Open Vein Harvest ( OVH ) , recent literature suggests that this may be at the expense of graft patency at one year and survival at three years . Methods We undertook a retrospective single-centre , single-surgeon , case-control study of EVH ( n = 89 ) and OVH ( n = 182 ) . The primary endpoint was death with secondary endpoints including acute coronary syndrome , revascularisation or other major adverse cardiac events . Freedom from angina , wound complications and self-rated health status were also assessed . Where repeat angiography had been performed , this was review ed . Results Both groups were well matched demographically and for peri-operative characteristics . All cause mortality was 2/89 ( 2 % ) and 11/182 ( 6 % ) in the EVH and OVH groups respectively . This was shown by Cox Log-Rank analysis to be non-significant ( p = 0.65 ) , even if adjusting for inpatient mortality ( p = 0.74 ) . There was no difference in the rates of freedom from angina ( p = 1.00 ) , re-admission ( p = 0.78 ) or need for further anti-anginals ( p = 1.00 ) . There was a significant reduction in the incidence of Output:	Results Compared with open vein harvest , it is reasonable to perform endoscopic vein harvest of saphenous vein to reduce wound-related complications , postoperative length of stay , and outpatient wound management re sources and to increase patient satisfaction ( class I , level A ) . Based on the quality of the conduit and major adverse cardiac events as well as 6-month angiographic patency , endoscopic vein harvest was noninferior to open harvest . Conclusions Based on the consensus statements , the consensus panel recommends ( class I , level B ) that endoscopic saphenous vein and radial artery harvesting should be the st and ard of care for patients who require these conduits for coronary revascularization
MS2994	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Cognitive deficits form core features in schizophrenia . Several studies have shown improvements in prefrontal cognitive function by α 2 -agonists in schizophrenia . In the present study , it was investigated whether clonidine ( an α 2 -adrenoceptor agonist ) could normalize sensorimotor gating deficits in schizophrenia . METHODS In a double blind , placebo controlled , r and omized , yet balanced , cross-over experiment , 20 male schizophrenia patients on stable medication were assessed in an auditory prepulse inhibition ( PPI ) , sensitization , and habituation of the startle reflex paradigm on 5 occasions : once after oral administration of placebo and after a single dose of 25 , 50 , 75 , and 150 µg of clonidine . Their results were compared with 20 age- and gender-matched healthy volunteers , who received no treatment . RESULTS In the placebo treatment , patients showed deficient PPI and sensitization , yet normal habituation compared with the controls . Except the highest dose , all dosages of clonidine significantly increased percentage PPI in the patients compared with placebo , to such levels that it no longer differed significantly from the healthy controls . However , none of the dosages increased sensitization or influenced habituation . CONCLUSIONS This is the first study to show that even a single low dose of clonidine added to the medical treatment of patients with schizophrenia who are clinical ly stable on their antipsychotic medication not only significantly ameliorates their PPI deficits , but also normalizes them . The results have a potentially high clinical relevance for the medical treatment of schizophrenia Adjunctive mirtazapine improved negative symptoms of schizophrenia in several studies . Recently , we found an improvement also in positive symptoms when mirtazapine was added to first generation antipsychotics ( FGAs ) in a 6 week r and omized controlled trial ( RCT ) . The short duration of that trial was its limitation . This study aim ed to explore whether longer treatment is worthwhile Major depressive disorder ( MDD ) has been associated with alterations in the noradrenergic system and impaired memory function . In turn , enhanced memory function has been associated with noradrenergic stimulation . In this study , we examined whether noradrenergic stimulation would differentially improve memory function in patients with MDD and healthy controls . In a placebo-controlled crossover study , 20 patients with MDD and 18 age- and sex-matched healthy controls received either placebo or 5 mg of yohimbine , an alpha-2-adrenoceptor antagonist that causes increased noradrenergic activity , orally before memory testing . A word list paradigm was used to test memory consolidation . Furthermore , the autobiographical memory test assessing memory retrieval and a working memory test were administered . Salivary alpha-amylase and blood pressure were measured . Yohimbine improved memory consolidation ( word list learning ) across groups ( main effect of yohimbine : p = 0.05 ) . This effect was more prominent in depressed patients compared with controls ( post hoc t-test : MDD p = 0.01 , controls p = 0.77 ) . Memory retrieval ( autobiographical memory specificity ) and working memory were not affected by yohimbine . Across groups , yohimbine administration result ed in an increase in blood pressure and alpha-amylase . In sum , these results further support the hypothesis that noradrenergic stimulation enhances memory consolidation . The mechanism by which yohimbine leads to stronger memory consolidation in depressed patients compared with healthy controls remains to be eluci date BACKGROUND Due to their favorable side-effect profile , atypical antipsychotic agents offer important therapeutic advantages in mood disorders . Ziprasidone , an atypical antipsychotic agent with strong 5-HT(1A ) agonist activity , may be particularly useful when used in conjunction with st and ard antidepressants in treatment-resistant depression . The purpose of this study is to test this hypothesis in depressed out patients who have not experienced significant clinical improvement following an adequate trial of a selective serotonin reuptake inhibitor ( SSRI ) . METHOD Twenty patients with major depressive disorder ( MDD ) who had failed to experience a clinical response to an adequate trial of an SSRI were treated with open-label ziprasidone in addition to their SSRI for 6 weeks between February 2002 and December 2002 . MDD was diagnosed with the Structured Clinical Interview for DSM-IV Axis I disorders . Clinical response was defined as a 50 % or greater decrease in depressive symptoms during the course of the trial ( baseline to endpoint ) , as measured by the HAM-D-17 total score . RESULTS Thirteen of 20 patients ( 65.0 % ) completed the trial . Using a completer analysis , 8 patients ( 61.5 % ) were classified as responders . An intent-to-treat ( ITT ) analysis result ed in 10 responders ( 50.0 % ) . The overall proportion of remitters was 5 of 13 ( 38.5 % ) using a completer analysis and 5 of 20 ( 25.0 % ) using the ITT analysis . Ziprasidone administration appeared to be safe , with no clinical ly significant QTc prolongation or severe adverse events observed in any of the study participants . CONCLUSION These results suggest a possible augmentation role for ziprasidone when used in conjunction with SSRIs in SSRI-resistant MDD BACKGROUND The comparative antidepressant effects of clozapine and other atypical antipsychotics for schizophrenia remain elusive , leading us to examine this question using the data from the Clinical Antipsychotic Trials of Intervention Effectiveness phase 2E . METHODS Ninety-nine patients who discontinued treatment with olanzapine , quetiapine , risperidone , or ziprasidone because of inadequate efficacy were r and omly assigned to open-label treatment with clozapine ( n=49 ) or double-blind treatment with another atypical antipsychotic not previously received in the trial ( olanzapine [ n=19 ] , quetiapine [ n=15 ] , or risperidone [ n=16 ] ) . The primary outcome was the Calgary Depression Scale for Schizophrenia ( CDSS ) total score . Antidepressant effects of clozapine and the other atypical antipsychotics were compared in patients with chronic schizophrenia and those with a major depressive episode ( MDE ) at baseline ( i.e. ≥6 on the CDSS ) , using mixed models . RESULTS No differences in the baseline CDSS total scores were found between the treatment groups regardless of presence of an MDE . Clozapine was more effective than quetiapine in antidepressant effects for chronic schizophrenia ( p<.01 for the whole sample and p=.01 for those with an MDE ) , and comparable to olanzapine and risperidone . CONCLUSION The present findings suggest that clozapine demonstrates superior antidepressant effects to quetiapine and comparable effects to olanzapine and risperidone in chronic schizophrenia regardless of presence of MDE . Given the indication of clozapine for treatment-resistant schizophrenia ( TRS ) and the negative impacts of depressive symptoms on clinical outcomes in schizophrenia , further research is warranted to investigate antidepressant effects of clozapine in TRS with an MDE OBJECTIVE Major depressive disorder has been linked with inflammatory processes , but it is unclear whether individual differences in levels of inflammatory biomarkers could help match patients to treatments that are most likely to be beneficial . The authors tested the hypothesis that C-reactive protein ( CRP ) , a commonly available marker of systemic inflammation , predicts differential response to escitalopram ( a serotonin reuptake inhibitor ) and nortriptyline ( a norepinephrine reuptake inhibitor ) . METHOD The hypothesis was tested in the Genome-Based Therapeutic Drugs for Depression ( GENDEP ) study , a multicenter open-label r and omized clinical trial . CRP was measured with a high-sensitivity method in serum sample s from 241 adult men and women with major depressive disorder r and omly allocated to 12-week treatment with escitalopram ( N=115 ) or nortriptyline ( N=126 ) . The primary outcome measure was the score on the Montgomery-Åsberg Depression Rating Scale ( MADRS ) , administered weekly . RESULTS CRP level at baseline differentially predicted treatment outcome with the two antidepressants ( CRP-drug interaction : β=3.27 , 95 % CI=1.65 , 4.89 ) . For patients with low levels of CRP ( < 1 mg/L ) , improvement on the MADRS score was 3 points higher with escitalopram than with nortriptyline . For patients with higher CRP levels , improvement on the MADRS score was 3 points higher with nortriptyline than with escitalopram . CRP and its interaction with medication explained more than 10 % of individual-level variance in treatment outcome . CONCLUSIONS An easily accessible peripheral blood biomarker may contribute to improvement in outcomes of major depressive disorder by personalizing treatment choice Background The Mental Health Biomarker Project ( 2010–2014 ) selected commercial biochemistry markers related to monoamine synthesis and metabolism and measures of visual and auditory processing performance . Within a case – control discovery design with exclusion criteria design ed to produce a highly characterised sample , results from 67 independently DSM IV-R-diagnosed cases of schizophrenia and schizoaffective disorder were compared with those from 67 control participants selected from a local hospital , clinic and community catchment area . Participants underwent protocol -based diagnostic-checking , functional-rating , biological sample - collection for thirty c and i date markers and sensory-processing assessment . Results Fifteen biomarkers were identified on ROC analysis . Using these biomarkers , odds ratios , adjusted for a case – control design , indicated that schizophrenia and schizoaffective disorder were highly associated with dichotic listening disorder , delayed visual processing , low visual span , delayed auditory speed of processing , low reverse digit span as a measure of auditory working memory and elevated levels of catecholamines . Other nutritional and biochemical biomarkers were identified as elevated hydroxyl pyrroline-2-one as a marker of oxidative stress , vitamin D , B6 and folate deficits with elevation of serum B12 and free serum copper to zinc ratio . When individual biomarkers were ranked by odds ratio and correlated with clinical severity , five functional domains of visual processing , auditory processing , oxidative stress , catecholamines and nutritional-biochemical variables were formed . When the strengths of their inter-domain relationships were predicted by Lowess ( non-parametric ) regression , predominant bidirectional relationships were found between visual processing and catecholamine domains . At a cellular level , the nutritional-biochemical domain exerted a pervasive influence on the auditory domain as well as on all other domains . Conclusions The findings of this biomarker research point towards a much-required advance in Psychiatry : quantification of some theoretically-underst and able , translationally-informative , treatment-relevant underpinnings of serious mental illness . This evidence reveals schizophrenia and schizoaffective disorder in a somewhat different manner , as a conglomerate of several disorders many of which are not currently being assessed-for or treated in clinical setting s. Currently available remediation techniques for these underlying conditions have potential to reduce treatment-resistance , relapse-prevention , cost burden and social stigma in these conditions . If replicated and vali date d in prospect i ve trials , such findings will improve progress-monitoring and treatment-response for schizophrenia and schizoaffective disorder No studies have compared mirtazapine with duloxetine in patients with major depressive disorder ( MDD ) . Fifty-six patients were nonr and omly assigned to a 4-week treatment with either 15 to 45 mg/day of mirtazapine ( n = 22 ) or 20 to 60 mg/day of duloxetine ( n = 34 ) . The primary efficacy measurements were the Hamilton Rating Scale for Depression ( HRSD ) and the Montgomery – Åsberg Depression 6-point Rating Scale ( MADRS ) scores . The second efficacy measurements were the response and remission rates of treatment . Tolerability assessment s were also performed . Fifty-six patients ( 43 male ; age , 43.6 years ) were recruited . There was no significant difference in the discontinuation rate between the mirtazapine and duloxetine treatment groups ( P = 0.867 ) . Both mirtazapine and duloxetine significantly improved the HRSD and MADRS scores from baseline ( P < 0.0001–0.0004 ) . While mirtazapine was superior to duloxetine in the reduction of HRSD scores ( P = 0.0421 ) , there was no significant change in MADRS scores in terms of between-group differences ( P = 0.171 ) . While more somnolence was observed with mirtazapine ( P = 0.0399 ) , more nausea was associated with duloxetine ( P = 0.0089 ) . No serious adverse events were observed for either antidepressant . Mirtazapine and duloxetine were safe and well-tolerated treatments for Japanese patients with MDD . Double-blind controlled studies are needed to further explore the efficacy and safety of mirtazapine and duloxetine in Japanese patients with MDD BACKGROUND Sensory gating deficits are Output:	Overall , the studies provided indirect evidence that α-AR activity may play an important role in aberrant regulation of cognition , arousal , and valence systems associated with MDD and schizophrenia . Characterization of the NE pathway in patients may provide clinicians with information for more personalized therapy of these heterogeneous diseases . Current clinical studies do not provide direct evidence to support the role of NE α-ARs in the pathophysiology of MDD and schizophrenia and in the treatment response of patients with these diseases , in particular with relation to specific valence systems .
MS2995	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Because leukotrienes have potent local effects on cutaneous vasculature , leukotriene antagonists might be effective in the treatment of chronic urticaria . OBJECTIVE A double-blinded , placebo-controlled trial comparing cetirizine 10 mg daily in combination with zafirlukast 20 mg twice a day versus cetirizine 10 mg daily and placebo was conducted to determine whether subjects with chronic urticaria benefit from add-on therapy with a leukotriene-modifying agent . METHODS Patients 12 years or older with a history of chronic urticaria ( more than 6 weeks in duration ) required diary documentation of 6 or more hives on at least 2 days/week and a suboptimal response to H(1)-antagonist therapy for enrollment . At baseline , all subjects were skin tested to autologous serum to assess for the potential presence of FcepsilonRI or IgE autoantibodies . Subjects meeting the initial entry criteria were treated with cetirizine 10 mg a day and placebo twice daily for 1 week . Those patients with persistent hives were r and omized to receive cetirizine 10 mg daily and zafirlukast 20 mg twice a day or cetirizine 10 mg daily and placebo . At each successive weekly visit , physician and patient treatment effectiveness score ( TES ) and visual analog scale ( VAS ) ratings were recorded . Statistical analysis used generalizing estimating equations to compare the effect of combination therapy versus monotherapy on TES and VAS ratings . Results were adjusted for baseline rating , recruiting center , and autologous serum skin test ( ASST ) . A separate analysis evaluated patients with positive ASST results receiving combination therapy versus monotherapy . RESULTS Combination therapy with zafirlukast demonstrated a modest but significantly greater improvement compared with cetirizine monotherapy in physician and patient recorded VAS ratings at visit 4 and across treatment visits 4 through 6 ( P < .05 unless stated otherwise ) . Subjects with ASST positive results receiving combination therapy as compared with subjects with negative ASST results exhibited a significant improvement in patient recorded VAS ratings across visits 4 through 6 . Subgroup analysis of subjects with ASST positive results receiving combination therapy versus monotherapy showed improvement in physician recorded TES at visit 5 , physician recorded VAS at visits 4 and 5 and across visits 4 through 6 , as well as for patient recorded VAS at visit 5 . There were no significant results for patients with ASST negative results . CONCLUSION The results of this study indicate that only patients with autoimmune ( ASST positive ) chronic urticaria refractory to H(1)-antagonist monotherapy might benefit from the addition of the leukotriene D(4)-receptor antagonist zafirlukast to their treatment regimen . These results also suggest that routine screening of patients with chronic urticaria with the ASST might be useful in formulating therapeutic algorithms in the management of chronic urticaria BACKGROUND Antihistamines ( AH ) alleviate pruritus and decrease the incidence of hives in patients with chronic idiopathic urticaria ( CU ) . However , some patients do not respond completely to this therapy . We hypothesized that some of them might benefit from the addition of leukotriene receptor antagonists ( LA ) . METHODS We screened patients diagnosed and treated for CU and selected those that had symptoms despite antihistamine treatment . In a double-blind crossover study , patients took the leukotriene antagonist montelukast ( 10 mg per day ) or placebo . Efficacy was assessed by a symptom score . RESULTS In a group of 22 patients , the symptom score was not significantly different between periods using montelukast ( 48.8 ; 0 - 214 ) or placebo ( 68.5 ; 0 - 230 ) . However in the subgroup of five patients with the most severe urticaria , defined as patients with symptom scores in the upper quartile at inclusion in the study , montelukast ( 41 ; 11 214 ) was superior to placebo ( 95.5 ; 48 230 ; p < 0.05 ) , but only when using an in-house symptom score question naire and not when using a vali date d urticaria activity score question naire . CONCLUSIONS We showed that in patients with antihistamine-resistant CU the addition of montelukast significantly diminished symptoms in only a small minority of patients . However , response to add-on montelukast was seen in the subgroup of patients with particularly severe disease . To confirm this observation , a study with a larger group of patients is warranted Background Chronic urticaria ( CU ) is a common skin condition . It is frequently a disabling disease due to the persistency of clinical symptoms , the unpredictable course and negative influence on the quality of life Background : Chronic idiopathic urticaria ( CIU ) is often difficult to treat . Although histamine-releasing activity is detectable for up to 50 % of CIU patients , antihistamine therapy provides only a limited response . Objective : This study aim ed to assess the clinical efficacy of combined leukotriene receptor antagonist ( LRA ) and H1 antihistamine , H1 and H2 antihistamine , and two H1 antihistamines as a synergistic therapeutic regimen for treating CIU compared with a matched placebo modality . Methods : A total of 120 newly diagnosed adult patients were evaluated . Patients were single blinded and r and omly assigned to one of four medication groups that received the following regimens for 4 weeks : Group A , combination of sedating H1 antihistamine and non-sedating H1 antihistamine ; Group B , combination of H1 antihistamine and H2 antihistamine ; Group C , combination of H1 antihistamine and LRA ; and Group D , matched placebo medication . The primary measure of treatment efficacy was the daily urticaria activity score ( UAS ) of ‘ wheal and itch ’ . A positive therapeutic response was defined as a reduction to < 25 % of baseline weekly UAS , while a relapse was a return to > 75 % of baseline weekly UAS . Results : In all , 107 patients completed the trial medication . At the end of 4 weeks , the UAS score as a response to treatment was 23.3 % for Group A , 63.3 % for Group B , 53.3 % for Group C , and no real change for the placebo treatment group . Conclusions : The combination of LRA and H1 receptor antagonist is promising for CIU treatment and is reasonably well tolerated by patients . The combination of H1- and H2-receptor antagonists provided the greatest treatment efficacy by the measures used in this small study BACKGROUND H 1 -receptor antagonists are considered to be particularly effective in reducing pruritus , and they are therefore recommended as first-line treatment in patients with chronic idiopathic urticaria ( CIU ) . Recently , antileukotriene receptors have been used in patients with CIU , either administered as monotherapy or combined with H 1 -receptor antagonists . OBJECTIVE We compared the clinical efficacy of 5 mg of desloratadine administered once daily either as monotherapy or combined with a leukotriene antagonist , 10 mg of montelukast daily , and 10 mg of montelukast administered daily as monotherapy for the treatment of patients affected by CIU with placebo . METHODS One hundred sixty patients aged 18 to 69 years ( mean + /- SD , 43.9 + /- 13.4 years ) with a history of moderate CIU were selected . A r and omized , double-blind , double-dummy , placebo-controlled , parallel-group study design was used . Patients were treated with 5 mg of desloratadine once daily ( n = 40 ) , 10 mg of montelukast once daily ( n = 40 ) , 5 mg of desloratadine ( n = 40 ) in the morning plus montelukast in the evening , or matched placebo ( n = 40 ) . Assessment of treatment efficacy was based on scores of daily cutaneous symptoms evaluated reflectively and instantaneously . RESULTS Only the group treated with desloratadine as monotherapy or as combined therapy concluded the whole study . Twenty-seven of the 40 patients in the montelukast group and 35 of the 40 patients in the placebo group discontinued the treatment . As reflective evaluation , all groups showed significant differences compared with the placebo group in terms of total symptom score , number of hives , and size of largest hive . In addition to the pruritus , only the groups treated with desloratadine as monotherapy or combined therapy showed significant differences compared with those receiving placebo , whereas there were no differences between the montelukast and placebo groups . Finally , no differences were found between the desloratadine group and the desloratadine plus montelukast group . The instantaneous evaluation demonstrated similar results regarding the desloratadine group and the desloratadine plus montelukast group versus the placebo group , whereas there were no significant differences between the group treated with montelukast alone and the placebo group for pruritus and size of largest hive . No differences were found between the group treated with desloratadine alone and the desloratadine plus montelukast group . CONCLUSIONS The results of this comparative study demonstrate that desloratadine is highly effective for the treatment of patients affected by CIU . In addition , the regular combined therapy of desloratadine plus montelukast does not seem to offer a substantial advantage with respect to desloratadine as monotherapy in patients affected by moderate CIU BACKGROUND Chronic idiopathic urticaria ( CIU ) might be refractory to st and ard therapies . For the patients with severe unremitting CIU who have failed to benefit from conventional therapy with antihistamines , other effective and safe therapeutic modalities are required . OBJECTIVE A r and omized , single-blind , placebo-controlled crossover study was conducted to evaluate the efficacy and safety of the new selective leukotriene antagonist montelukast sodium in the treatment of refractory CIU . METHODS Thirty patients with refractory CIU were enrolled in the trial . After informed consent was obtained , patients were r and omly assigned to 2 groups . The patients in group A received 10 mg/d montelukast and a nonsedating H(1 ) antihistamine ( cetirizine ) when needed for 6 weeks . After a 2-week washout period , they received placebo for 6 weeks and the same H(1 ) antihistamine as needed . Group B received the treatment vice versa . Improvement was monitored by using the self-estimated urticaria activity score , which is the sum of the wheal number score and the itch severity score , and the antihistamine counts used in each study period . RESULTS More significant decreases occurred in urticaria activity scores with montelukast therapy compared with those with placebo therapy ( P < .001 ) . H(1 ) antihistamine use was also significantly less frequent during the montelukast period ( P < .001 ) . There were no significant side effects with montelukast therapy . CONCLUSION The present study results suggest that montelukast might be an effective and safe therapeutic agent in the treatment of refractory CIU Background Leukotriene receptor antagonists have shown some efficacy in the treatment of asthma . Injection of LTC4 , LTD4 and LTE4 into the skin leads to a weal‐ and ‐flare reaction , suggesting an involvement of leukotrienes in the pathogenesis of urticaria . Indeed , various reports have indicated a beneficial effect for leukotriene receptor antagonists in patients with chronic urticaria Background The cause and pathogenesis of chronic urticaria are still poorly understood . IgE‐independent reactions , are common in adult patients with chronic urticaria , who have daily spontaneous occurrence of weals . H1‐receptor antagonists ( antihistamines ) are the major class of therapeutic agents used in the management of urticaria and angioedema . Nevertheless , chronic urticaria is often difficult to treat and may not be controlled by antihistamines alone . It has been postulated that mediators other than histamine , such as kinins , prostagl and in and leukotrienes , may be responsible for some of the symptoms in urticaria which are not controlled by antihistamines . In this study , which was r and omized double‐blind , placebo‐controlled , we compare the clinical efficacy and safety of montelukast ( MT ) 10 mg given once a day and cetirizine ( CET ) 10 mg given once a day with placebo ( PLA ) , in the treatment of patients with chronic urticaria who have positive challenge to acetylsalicylic acid ( ASA ) and /or food additives Output:	Most trials indicated that LTRA are not superior to placebo or antihistamine therapy , while combination therapy of LTRA and antihistamines appear to be more efficacious compared to antihistamine alone . The side effect profile and tolerability of this group of drugs is acceptable . The use of LTRA as monotherapy can not be recommended . LTRA are effective add-on therapy to anti-histamines , and their use in patients responding poorly to antihistamines is justifiable .
MS2996	*TASK* the task is to summarize an input biomedical literature in six sentences *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 recent years quality of life instruments have been featured as primary outcomes in many r and omized trials . One of the challenges facing the investigator using such measures is determining the significance of any differences observed , and communicating that significance to clinicians who will be applying the trial results . We have developed an approach to elucidating the significance of changes in score in quality of life instruments by comparing them to global ratings of change . Using this approach we have established a plausible range within which the minimal clinical ly important difference ( MCID ) falls . In three studies in which instruments measuring dyspnea , fatigue , and emotional function in patients with chronic heart and lung disease were applied the MCID was represented by mean change in score of approximately 0.5 per item , when responses were presented on a seven point Likert scale . Furthermore , we have established ranges for changes in question naire scores that correspond to moderate and large changes in the domains of interest . This information will be useful in interpreting question naire scores , both in individuals and in groups of patients participating in controlled trials , and in the planning of new trials BACKGROUND Patients with diabetes and anemia are at high risk of cardiovascular disease . The Anemia CORrection in Diabetes ( ACORD ) Study aim ed to investigate the effect of anemia correction on cardiac structure , function , and outcomes in patients with diabetes with anemia and early diabetic nephropathy . METHODS One hundred seventy-two patients with type 1 or 2 diabetes mellitus , mild to moderate anemia , and stage 1 to 3 chronic kidney disease were r and omly assigned to attain a target hemoglobin ( Hb ) level of either 13 to 15 g/dL ( 130 to 150 g/L ; group 1 ) or 10.5 to 11.5 g/dL ( 105 to 115 g/L ; group 2 ) . The primary end point was change in left ventricular mass index ( LVMI ) . Secondary end points included echocardiographic variables , renal function , quality of life , and safety . RESULTS Median Hb level and LVMI were similar in groups 1 and 2 ( Hb , 11.9 and 11.7 g/dL [ 119 and 117 g/L ] ; LVMI , 113.5 and 112.3 g/m(2 ) , respectively ) . At study end , Hb levels were 13.5 g/dL ( 135 g/L ) in group 1 and 12.1 g/dL ( 121 g/L ) in group 2 ( P < 0.001 ) . No significant differences were observed in median LVMI at month 15 between study groups ( group 1 , 112.3 g/m(2 ) ; group 2 , 116.5 g/m(2 ) ) . Multivariate analysis showed a nonsignificant decrease in LVMI ( P = 0.15 ) in group 1 versus group 2 . Anemia correction had no effect on the rate of decrease in creatinine clearance , but result ed in significantly improved quality of life in group 1 ( P = 0.04 ) . There were no clinical ly relevant differences in adverse events between study groups . CONCLUSION In patients with diabetes with mild to moderate anemia and moderate left ventricular hypertrophy , correction to an Hb target level of 13 to 15 g/dL ( 130 to 150 g/L ) does not decrease LVMI . However , normalization of Hb level prevented an additional increase in left ventricular hypertrophy , was safe , and improved quality of life BACKGROUND This r and omized clinical trial is design ed to assess whether the prevention and /or correction of anemia , by immediate versus delayed treatment with erythropoietin alfa in patients with chronic kidney disease , would delay left ventricular ( LV ) growth . Study design and sample size calculations were based on previously published Canadian data . METHODS One hundred seventy-two patients were r and omly assigned . The treatment group received therapy with erythropoietin alfa subcutaneously to maintain or achieve hemoglobin ( Hgb ) level targets of 12.0 to 14.0 g/dL ( 120 to 140 g/L ) . The control/delayed treatment group had Hgb levels of 9.0 + /- 0.5 g/dL ( 90 + /- 5 g/L ) before therapy was started : target level was 9.0 to 10.5 g/dL ( 90 to 105 g/L ) . Optimal blood pressure and parathyroid hormone , calcium , and phosphate level targets were prescribed ; all patients were iron replete . The primary end point is LV growth at 24 months . RESULTS One hundred fifty-two patients were eligible for the intention-to-treat analysis : mean age was 57 years , 30 % were women , 38 % had diabetes , and median glomerular filtration rate was 29 mL/min ( 0.48 mL/s ; range , 12 to 55 mL/min [ 0.20 to 0.92 mL/s ] ) . Blood pressure and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use were similar in the control/delayed treatment and treatment groups at baseline . Erythropoietin therapy was administered to 77 of 78 patients in the treatment group , with a median final dose of 2,000 IU/wk . Sixteen patients in the control/delayed treatment group were administered erythropoietin at a median final dose of 3,000 IU/wk . There was no statistically significant difference between groups for the primary outcome of mean change in LV mass index ( LVMI ) from baseline to 24 months , which was 5.21 + /- 30.3 g/m2 in the control/delayed treatment group versus 0.37 + /- 25.0 g/m2 in the treatment group . Absolute mean difference between groups was 4.85 g/m2 ( 95 % confidence interval , -4.0 to 13.7 ; P = 0.28 ) . Mean Hgb level was greater in the treatment group throughout the study and at study end was 12.75 g/dL ( 127.5 g/L in treatment group versus 11.46 g/dL [ 114.6 g/L ] in control/delayed treatment group ; P = 0.0001 ) . LV growth occurred in 20.1 % in the treatment group versus 31 % in the control/delayed treatment group ( P = 0.136 ) . In patients with a stable Hgb level , mean LVMI did not change ( -0.25 + /- 26.7 g/m2 ) , but it increased in those with decreasing Hgb levels ( 19.3 + /- 28.2 g/m2 ; P = 0.002 ) . CONCLUSION This trial describes disparity between observational and r and omized controlled trial data : observed and r and omly assigned Hgb level and LVMI are not linked ; thus , there is strong evidence that the association between Hgb level and LVMI likely is not causal . Large r and omized controlled trials with unselected patients , using morbidity and mortality as outcomes , are needed The investigators evaluated the impact of recombinant human erythropoietin ( r-HuEPO ) therapy on health-related quality of life ( HRQL ) in predialysis chronic renal disease patients with anemia . Eighty-three patients were entered into a r and omized , parallel-group , open-label clinical trial with follow-up evaluations over 48 weeks . Forty-three patients were assigned to r-HuEPO treatment , and 40 patients were assigned to an untreated control group . Hematocrit levels were measured at baseline and monthly . HRQL was assessed at baseline and at weeks 16 , 32 , and 48 . The HRQL assessment included measures of physical function , energy , role function , health distress , cognitive function , social function , home management , sexual dysfunction , depression , and life satisfaction . Significant improvements in hematocrit levels were observed in the r-HuEPO-treated group ( P < 0.0001 ) , and no changes were seen in the untreated group . Correction of anemia ( hematocrit > or = 36 ) occurred in 79 % of r-HuEPO-treated patients and 0 % of control patients . Significant improvements in assessment s of energy ( P < 0.05 ) , physical function ( P < 0.05 ) , home management ( P < 0.05 ) , social activity ( P < 0.05 ) , and cognitive function ( P < 0.05 ) were found for the r-HuEPO-treated group . No changes were observed in the control group , except for a decrease in physical function ( P < 0.05 ) . Between-group differences favoring the r-HuEPO-treated group were found for energy ( P < 0.05 ) and physical functioning ( P < 0.05 ) . In patients receiving r-HuEPO , significant improvements were seen in hemotocrit levels , and these increases result ed in improvements in HRQL BACKGROUND This study is design ed to assess the effect of early and complete correction of anemia by using recombinant human erythropoietin ( epoetin ) alfa on the progression of chronic kidney disease ( CKD ) . METHODS Patients were r and omly assigned to achieve high ( 13 to 15 g/dL [ 130 to 150 g/L ] ) or low ( 11 to 12 g/dL [ 110 to 120 g/L ] ) hemoglobin-level targets during 4 months of stabilization , followed by 36 months of maintenance . Glomerular filtration rate ( GFR ) decrease was measured by using iohexol clearance . Quality of life , nutrition , and safety also were monitored . RESULTS Because of labeling changes for subcutaneous administration of epoetin alfa ( Eprex ; Johnson and Johnson , Schaffhausen , Switzerl and ) , the study was terminated prematurely . There were 195 patients enrolled in each group ; 108 high-hemoglobin and 133 low-hemoglobin patients entered the maintenance phase . Mean maintenance duration was 7.4 months for the high-hemoglobin group and 8.3 months for the low-hemoglobin group . GFR decrease was numerically , but not statistically significantly , lower with the high-hemoglobin group ( 0.058 versus 0.081 mL/min/1.73 m2/mo [ < 0.01 mL/s/1.73 m2/mo ] ) . Physical quality -of-life measures showed trends ( Role-Physical , P = 0.055 ; Physical Function , P = 0.083 ) or statistically significant improvement ( Vitality , P = 0.042 ) with high hemoglobin levels at the end of the stabilization phase . Adverse events were similar between groups . Cardiovascular adverse events occurred in 25 % of the high-hemoglobin and 18 % of the low-hemoglobin patients ( P = 0.137 ) . Neither epoetin dosage nor hemoglobin level was associated with cardiovascular adverse events or death . CONCLUSION These data suggest that normalization of hemoglobin levels in patients with CKD is safe . Longer duration studies are needed to clarify efficacy benefits with high hemoglobin levels BACKGROUND Partial correction of renal anaemia with erythropoietin improves quality of life ( QoL ) . We aim ed to examine if normalization of haemoglobin with epoetin alfa in pre-dialysis and dialysis patients further improves QoL and is safe . METHODS 416 Sc and inavian patients with renal anaemia [ pre-dialysis , haemodialysis ( HD ) and peritoneal dialysis patients ] were r and omized to reach a normal haemoglobin of 135 - 160 g/l ( n=216 ) or a subnormal haemoglobin of 90 - 120 g/l ( n=200 ) with or without epoetin alfa . Study duration was 48 - 76 weeks . QoL was measured using Kidney Disease Question naires in 253 Swedish dialysis patients . Safety was examined in all patients . RESULTS QoL improved , measured as a decrease in physical symptoms ( P=0.02 ) , fatigue ( P=0.05 ) , depression ( P=0.01 ) and frustration ( P=0.05 ) in the Swedish dialysis patients when haemoglobin was normalized . In pre-dialysis patients , diastolic blood pressure was higher in the normal compared with the subnormal haemoglobin group after 48 weeks . However , the progression rate of chronic renal failure was comparable . In the normal haemoglobin group ( N-Hb ) , 51 % had at least one serious adverse event compared with 49 % in the subnormal haemoglobin group ( S-Hb ) ( P=0.32 ) . The incidence of thrombovascular events and vascular access thrombosis in HD patients did not differ . The mortality rate was 13.4 % in the N-Hb group and 13.5 % in the S-Hb group ( P=0.98 ) . Mortality decreased with increasing mean haemoglobin in both groups . CONCLUSIONS Normalization of haemoglobin improved QoL in the subgroup of dialysis patients , appears to be safe and can be considered in many patients with end-stage renal disease BACKGROUND In patients with end-stage renal disease , anemia develops as a result of erythropoietin deficiency , and recombinant human erythropoietin ( epoetin ) is prescribed to correct Output:	Our study suggests that targeting hemoglobin levels in excess of 12.0 g/dL leads to small and not clinical ly meaningful improvements in HQOL . This , in addition to significant safety concerns , suggests that targeting treatment to hemoglobin levels that are in the range of 9.0 to 12.0 g/dL is preferred
MS2997	*TASK* the task is to summarize an input biomedical literature in six sentences *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 Shock-absorbing and biomechanic shoe orthoses are frequently used in the prevention and treatment of back and lower extremity problems . One review concludes that the former is clinical ly effective in relation to prevention , whereas the latter has been tested in only 1 r and omized clinical trial , concluding that stress fractures could be prevented . OBJECTIVES To investigate if biomechanic shoe orthoses can prevent problems in the back and lower extremities and if reducing the number of days off-duty because of back or lower extremity problems is possible . DESIGN Prospect i ve , r and omized , controlled intervention trial . STUDY SUBJECTS One female and 145 male military conscripts ( aged 18 to 24 years ) , representing 25 % of all new conscripts in a Danish regiment . METHOD Health data were collected by question naires at initiation of the study and 3 months later . Custom-made biomechanic shoe orthoses to be worn in military boots were provided to all in the study group during the 3-month intervention period . No intervention was provided for the control group . Differences between the 2 groups were tested with the chi-square test , and statistical significance was accepted at P < .05 . Risk ratio ( RR ) , risk difference ( ARR ) , numbers needed to prevent ( NNP ) , and cost per successfully prevented case were calculated . OUTCOME VARIABLES Outcome variables included self-reported back and /or lower extremity problems ; specific problems in the back or knees or shin splints , Achilles tendonitis , sprained ankle , or other problems in the lower extremity ; number of subjects with at least 1 day off-duty because of back or lower extremity problems and total number of days off-duty within the first 3 months of military service because of back or lower extremity problems . RESULTS Results were significantly better in an actual-use analysis in the intervention group for total number of subjects with back or lower extremity problems ( RR 0.7 , ARR 19 % , NNP 5 , cost 98 US dollars ) ; number of subjects with shin splints ( RR 0.2 , ARR 19 % , NNP 5 , cost 101 US dollars ) ; number of off-duty days because of back or lower extremity problems ( RR 0.6 , ARR < 1 % , NNP 200 , cost 3750 US dollars ) . In an intention-to-treat analysis , a significant difference was found for only number of subjects with shin splints ( RR 0.3 , ARR 18 % , NNP 6 cost 105 US dollars ) , whereas a worst-case analysis revealed no significant differences between the study groups . CONCLUSIONS This study shows that it may be possible to prevent certain musculoskeletal problems in the back or lower extremities among military conscripts by using custom-made biomechanic shoe orthoses . However , because care-seeking for lower extremity problems is rare , using this method of prevention in military conscripts would be too costly . We also noted that the choice of statistical approach determined the outcome Study Design . R and omized controlled trial . Objectives . To determine if the use of custom shoe orthoses can lessen the incidence of weight bearing-induced back pain . Summary of Background Data . The scientific basis for the use of orthoses to prevent back pain is based principally on studies that show that shoe orthoses can attenuate the shock wave generated at heel strike . The repetitive impulsive loading that occurs because of this shock wave can cause wear of the mechanical structures of the back . Previous r and omized studies showed mixed results in preventing back pain , were not blinded , and used orthoses for only short periods of time . Methods . A total of 404 eligible new infantry recruits without a history of prior back pain were r and omly assigned to received either custom soft , semirigid biomechanical , or simple shoe inserts without supportive or shock absorbing qualities . Recruits were review ed biweekly by an orthopaedist for back signs and symptoms during the course of 14 weeks of basic training Results . The overall incidence of back pain was 14 % . By intention-to treat and per- protocol analyses , there was no statistically significant difference between the incidence of either subjective or objective back pain among the 3 treatment groups . Significantly more recruits who received soft custom orthoses finished training in their assigned orthoses ( 67.5 % ) than those who received semirigid biomechanical orthoses ( 45.5 % ) or simple shoe inserts ( 48.6 % ) , P = 0.001 . Conclusions . The results of this study do not support the use of orthoses , either custom soft or semirigid biomechanical , as prophylactic treatment for weight bearing-induced back pain . Custom soft orthoses had a higher utilization rate than the semirigid biomechanical or simple shoe inserts . The pretraining physical fitness and sports participation of recruits were not related to the incidence of weight bearing-induced back pain & NA ; Pain intensity is frequently measured on an 11‐point pain intensity numerical rating scale ( PI‐NRS ) , where 0=no pain and 10=worst possible pain . However , it is difficult to interpret the clinical importance of changes from baseline on this scale ( such as a 1‐ or 2‐point change ) . To date , there are no data driven estimates for clinical ly important differences in pain intensity scales used for chronic pain studies . We have estimated a clinical ly important difference on this scale by relating it to global assessment s of change in multiple studies of chronic pain . Data on 2724 subjects from 10 recently completed placebo‐controlled clinical trials of pregabalin in diabetic neuropathy , postherpetic neuralgia , chronic low back pain , fibromyalgia , and osteoarthritis were used . The studies had similar design s and measurement instruments , including the PI‐NRS , collected in a daily diary , and the st and ard seven‐point patient global impression of change ( PGIC ) , collected at the endpoint . The changes in the PI‐NRS from baseline to the endpoint were compared to the PGIC for each subject . Categories of ‘ much improved ’ and ‘ very much improved ’ were used as determinants of a clinical ly important difference and the relationship to the PI‐NRS was explored using graphs , box plots , and sensitivity/specificity analyses . A consistent relationship between the change in PI‐NRS and the PGIC was demonstrated regardless of study , disease type , age , sex , study result , or treatment group . On average , a reduction of approximately two points or a reduction of approximately 30 % in the PI‐NRS represented a clinical ly important difference . The relationship between percent change and the PGIC was also consistent regardless of baseline pain , while higher baseline scores required larger raw changes to represent a clinical ly important difference . The application of these results to future studies may provide a st and ard definition of clinical ly important improvement in clinical trials of chronic pain therapies . Use of a st and ard outcome across chronic pain studies would greatly enhance the comparability , validity , and clinical applicability of these studies The prevalence and incidence of low back pain in general society is high . Workers whose job involves walking long distances have an even higher tendency to suffer from low back pain . A positive effect of insoles in reducing low back pain was found in professional sports players . This was not examined on people whose job involves walking long distances . In this double blind prospect i ve study we examined the effectiveness of insoles constructed in a computerized method to placebo insoles in 58 employees whose work entailed extensive walking and who suffered from low back pain . The evaluation was performed by the MILLION question naire , which is considered as a valid question naire for evaluation of low back pain . We calculated the differences of the pain intensity before and after the intervention , in the employees using the insoles manufactured by computer in comparison to the users of the placebo insoles . In each group , the analysis was performed in comparison to the baseline . A total of 81 % of the employees preferred the real insoles as effective and comfortable in comparison to 19 % of the users of the placebo insoles ( P<0.05 ) . The results of this study indicate a substantial improvement in the low back pain after the use of the true insoles . The average pain intensity according to the MILLION question naire before the use of the insoles was 5.46 . However , after the use of the real insoles and the placebo insoles , the average pain intensity decreased to 3.96 and 5.11 , respectively . The difference of the average pain intensity at the start of the study and after the use of the real insoles was significant : −1.49 ( P=0.0001 ) , whereas this difference after the use of the placebo insoles was not significant : −0.31 ( P=0.1189 ) . The reported severity of pain also decreased significantly : a level 5 pain and above was reported by 77 % of the subjects at the start of the study . After the use of the real insoles only 37.9 % of the subjects reported a similar degree of pain severity , and 50 % of the subjects did so after the use of the placebo insoles ( P < 0.05 ) . We did not find a link between low back pain and other variables such as gender , age , number of offspring , work seniority , smoking , previous use of insoles and previous medication . This study demonstrates that the low back pain decreased significantly after the use of real insoles compared to placebo ones Sedentary individuals , particularly new military recruits , who start a physical training program have a substantial risk of developing an overuse injury of the lower limb . In this study we investigated the effect of neoprene insoles on the incidence of overuse injuries during 9 weeks of basic military training . The experimental group consisted of 237 r and omly selected new recruits , while 1151 recruits were the control group . Insoles were given to the experimental group and compliance was monitored . A panel of doctors documented and classi fied all injuries occurring during the 9 week period . A total of 54 ( 22.8 % ) and 237 ( 31.9 % ) injuries were reported in the experimental and control groups , re spectively . In both groups , the majority of injuries were overuse ( experimental group , 90.7 % ; control group , 86.4 % ) . The mean weekly incidence of total overuse injuries and tibial stress syndrome was significantly lower ( P < 0.05 ) in the experimental group . The mean incidence of stress fractures was lower in the experimental group but not significantly so ( 0.05 < P < 0.1 ) . This study shows that the incidence of total overuse injuries and tibial stress syndrome during 9 weeks of basic military training can be reduced by wearing insoles The purpose of this study was to assess the effect of viscoelastic shoe inserts on pain in nursing students . Students ( N = 100 ) were r and omly assigned to control and viscoelastic groups . The viscoelastic group used viscoelastic insoles in their work shoes for five weeks . A pain question naire was used to measure location and intensity of post-work pain . The question naire was administered as a pre-test and after five weeks . Post-test comparisons between groups indicated significant differences which were not present at pre-test . The viscoelastic group reported a significant peripheral shift in pain location from back to lower extremity ; the viscoelastic group also showed significant changes in duration of post-work pain and frequency of pain during the workday . The clinical efficacy of viscoelastic shoe inserts for modifying weight bearing-induced back pain is supported . Further clinical research into the therapeutic and prophylactic value of shock-attenuating shoe inserts for healthy as well as patient population s is advocated Output:	There is strong evidence that the use of insoles does not prevent back pain . There is limited evidence that insoles alleviate back pain or adversely shift the pain to the lower extremities . CONCLUSION There is strong evidence that insoles are not effective for the prevention of back pain .
MS2998	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND We conducted a prospect i ve , multicenter , r and omized comparison of implantable cardioverter-defibrillator ( ICD ) versus antiarrhythmic drug therapy in survivors of cardiac arrest secondary to documented ventricular arrhythmias . METHODS AND RESULTS From 1987 , eligible patients were r and omized to an ICD , amiodarone , propafenone , or metoprolol ( ICD versus antiarrhythmic agents r and omization ratio 1:3 ) . Assignment to propafenone was discontinued in March 1992 , after an interim analysis conducted in 58 patients showed a 61 % higher all-cause mortality rate than in 61 ICD patients during a follow-up of 11.3 months . The study continued to recruit 288 patients in the remaining 3 study groups ; of these , 99 were assigned to ICDs , 92 to amiodarone , and 97 to metoprolol . The primary end point was all-cause mortality . The study was terminated in March 1998 , when all patients had concluded a minimum 2-year follow-up . Over a mean follow-up of 57+/-34 months , the crude death rates were 36.4 % ( 95 % CI 26.9 % to 46.6 % ) in the ICD and 44.4 % ( 95 % CI 37.2 % to 51.8 % ) in the amiodarone/metoprolol arm . Overall survival was higher , though not significantly , in patients assigned to ICD than in those assigned to drug therapy ( 1-sided P=0.081 , hazard ratio 0.766 , [ 97.5 % CI upper bound 1.112 ] ) . In ICD patients , the percent reductions in all-cause mortality were 41.9 % , 39.3 % , 28 . 4 % , 27.7 % , 22.8 % , 11.4 % , 9.1 % , 10.6 % , and 24.7 % at years 1 to 9 of follow-up . CONCLUSIONS During long-term follow-up of cardiac arrest survivors , therapy with an ICD is associated with a 23 % ( nonsignificant ) reduction of all-cause mortality rates when compared with treatment with amiodarone/metoprolol . The benefit of ICD therapy is more evident during the first 5 years after the index event Background Carvedilol therapy has been reported to be more effective than other beta-blockers in patients with chronic heart failure ( CHF ) . Amiodarone is an anti-arrhythmic medicine that has also been reported to be effective in patients with CHF . But the usefulness of combined therapy with carvedilol and amiodarone has not been reported . Methods We compared 15 patients ( M/F=3/12 , age=57±8 y ) with dilated cardiomyopathy ( DCM ) receiving carvedilol and amiodarone with 15 patients ( M/F=3/12 , age=61±9 y ) receiving carvedilol alone . Patients were studied before and after 1 year of treatment ( 1Y ) . NYHA class and exercise capacity based on the specific-activity-scale ( SAS ) , were assessed . Cardiac sympathetic nerve activity was estimated using total defect score ( TDS ) , H/M ratio and washout rate ( WR ) of 123I-MIBG imaging . Cardiac function was evaluated using 99mTc-MIBI QGS . Results Combined , therapy improved several parameters much more than carvedilol alone ( p<0.05 ) including delta-TDS ( 15.0±8.6 vs. 7.6±7.2 ) and delta- WR ( 15.9±11.0 % vs. 7.3±10.0 % ) for 123I-MIBG imaging , delta-LVEF ( 26.1±11.4 % vs. 15.5±13.8 % ) , delta-endsystolic volume ( 100±63.8 ml vs. 58.9±47.3 ml ) , 1Y NYHA class ( 1.5±0.5 vs. 1.9±0.5 ) , 1Y SAS ( 7.3±0.7 Mets vs. 6.2±1.0 Mets ) , and delta-SAS ( 3.4±0.8 Mets vs. 2.6±1.1 Mets ) . Conclusion Combined therapy with carvedilol and amiodarone is more effective in improving cardiac symptoms , exercise capacity , cardiac function and cardiac sympathetic nerve activity in patients with DCM Background In the Basel Antiarrhythmic Study of Infa rct Survival trial , low-dose amiodarone improved 1-year survival in patients with asymptomatic complex ventricular arrhythmias persisting 2 weeks after myocardial infa rct ion . To assess whether this beneficial effect persisted despite discontinuation of amiodarone after 1 year , the long-term outcomes of all patients of the amiodarone-treated group ( initially n=98 ) and those of the control group ( n=114 ) were assessed . Methods and Results After a mean follow-up of 72 ( 55–125 ) months , information on 96 % of patients ( 203 of 212 ) was obtained regarding survival or cause of death . The probability of death after 84 months according to actuarial life-table analysis ( Kaplan-Meier ) was 30%1 for the amiodarone-treated patients and 45 % for control patients . For the total follow-up , mortality remained significantly lower in the amiodarone group versus the control group regarding all deaths ( p=0.03 ) as well as cardiac death ( p=0.047 ) . This mortality reduction was entirely due to the first-year amiodarone effect , since there was no significant mortality difference between groups when considering survival after discontinuation of amiodarone only . Conclusion These data suggest that the beneficial effect of amiodarone on survival in this high-risk group of patients persists for several years . In addition , the results stress the importance of early treatment after myocardial infa rct ion , whereas the rate of sudden death and all cardiac death is low ( 1.6 % and 4.1 % per year , respectively ) during late follow-up and therefore may not warrant further therapy Background — Corresponding with a continuing decline in the prevalence of sudden cardiac arrest cases presenting with ventricular fibrillation ( VF ) , there has been a significant rise in the prevalence of pulseless electrical activity ( PEA ) . Given significantly lower survival from PEA versus VF , we comprehensively investigated PEA correlates by incorporating first-responder data with lifetime clinical history information . Methods and Results — In the Portl and , Ore , metropolitan area ( population ≈1 million ) , cases of out-of-hospital sudden cardiac arrest who underwent attempted resuscitation were identified prospect ively ( 2002–2007 ) . Those presenting with PEA versus VF and asystole were compared with & khgr;2 tests , ANOVA , and logistic regression . A total of 1277 cases aged ≥18 years underwent resuscitation by first responders ( mean age , 65±16 years ; 67 % male ) . Presenting arrhythmia was VF in 48 % , PEA in 25 % , and asystole/other in the remainder . Compared with VF cases , PEA cases were older ( mean age , 68 versus 63 years ; P=0.0002 ) , more likely to be female ( 37 % versus 26 % ; P=0.0008 ) , and less likely to survive to hospital discharge ( 6 % versus 25 % ; P<0.0001 ) . A history of syncope was strongly associated with PEA ( odds ratio , 2.6 ; confidence interval , 1.3 to 5.3 ) after adjustment for age , gender , response time , and arrest circumstances . Black race was also independently associated with PEA ( odds ratio , 2.6 ; confidence interval , 1.3 to 5.4 ) . Pulmonary disease and female gender were significant factors associated with PEA ( P for interaction=0.04 ) . In a subgroup analysis of resting ECGs ( n=391 ) , there were no differences in cardiac clinical history or prevalence of cardiac conduction system disease ( PEA , 31.6 % versus VF , 32.2 % ; P=0.48 ) . Conclusions — PEA cases had a significantly higher prevalence of syncope in their lifetime , with other correlates , including black race , that were distinct from VF cases . Potential mechanistic links between syncope and future manifestation with PEA warrant further exploration Objective : To study the therapeutic effects of low-dose amiodarone and Betaloc on hypertrophic cardiomyopathy complicated by malignant ventricular arrhythmias . Methods : Eighty-two such patients were selected and divided into a treatment group and a control group by the r and om number method ( n=41 ) , which were administered with low-dose amiodarone plus Betaloc and individual Betaloc respectively . Results : The treatment group had a significantly higher overall effective rate ( 85.4 % ) than the control group ( 65.9 % ) did . Based on the New York Heart Association 's classification of cardiovascular disease , the treatment group mainly comprised Class III and IV patients before treatment , which were significantly relieved after treatment ( P<0.05 ) . The heart rate was evidently decreased from ( 119.99±18.91 ) bpm to ( 80.98±12.34 ) bpm , and the incidences of premature ventricular contraction and tachycardia were significantly reduced ( P<0.05 ) . The longest QT intervals after and before treatment were ( 421±32 ) ms and ( 411±35 ) ms respectively . The shortest QT interval after treatment [ ( 350±36 ) ms ] was significantly longer than that before [ ( 307±31 ) ms ] . The QT dispersion before treatment [ ( 96±29 ) ms ] was significantly higher that after [ ( 64±17 ) ms ] ( P<0.05 ) . Six out of eighty two patients in the treatment group succumbed to adverse reactions ( 14.63 % ) . Conclusion : Hypertrophic cardiomyopathy complicated with malignant ventricular arrhythmias can be well treated with low-dose amiodarone and Betaloc , with mitigated symptoms , improved prognosis and few adverse reactions OBJECTIVES The purpose of this multicenter r and omized trial was to compare total mortality during therapy with amiodarone or an implantable cardioverter-defibrillator ( ICD ) in patients with nonischemic dilated cardiomyopathy ( NIDCM ) and nonsustained ventricular tachycardia ( NSVT ) . BACKGROUND Whether an ICD reduces mortality more than amiodarone in patients with NIDCM and NSVT is unknown . METHODS One hundred three patients with NIDCM , left ventricular ejection fraction < or = 0.35 , and asymptomatic NSVT were r and omized to receive either amiodarone or an ICD . The primary end point was total mortality . Secondary end points included arrhythmia-free survival , quality of life , and costs . RESULTS The study was stopped when the prospect i ve stopping rule for futility was reached . The percent of patients surviving at one year ( 90 % vs. 96 % ) and three years ( 88 % vs. 87 % ) in the amiodarone and ICD groups , respectively , were not statistically different ( p = 0.8 ) . Quality of life was also similar with each therapy ( p = NS ) . There was a trend with amiodarone , as compared to the ICD , towards improved arrhythmia-free survival ( p = 0.1 ) and lower costs during the first year of therapy ( $ 8,879 US dollars vs. $ 22,039 US dollars , p = 0.1 ) . CONCLUSIONS Mortality and quality of life in patients with NIDCM and NSVT treated with amiodarone or an ICD are not statistically different . There is a trend towards a more beneficial cost profile and improved arrhythmia-free survival with amiodarone therapy Background —Sudden cardiac death ( SCD ) is a leading cause of death in the United States , but the relative public health burden is unknown . We estimated the burden of premature death from SCD and compared it with other diseases . Methods and Results —Analyses were based on the following data sources ( using most recent sources that provided appropriately stratified data ): ( 1 ) leading causes of death among men and women from 2009 US death certificate reporting ; ( 2 ) individual cancer mortality rates from 2008 death certificate reporting from the Centers for Disease Control and Prevention ’s National Program of Cancer Registries ; ( 3 ) county , state , and national population data for 2009 from the US Census Bureau ; and ( 4 ) SCD rates from the Oregon Sudden Unexpected Death Study ( SUDS ) population -based surveillance study of SCD between 2002 and 2004 . Cases were identified from multiple sources in a prospect ively design ed surveillance program . Incidence , counts , and years of potential life lost for SCD and other major diseases were compared . The age-adjusted national incidence of SCD was 60 per 100 000 population ( 95 % confidence interval , 54–66 per 100 000 ) . The burden of premature death for men ( 2.04 million years of potential life lost ; 95 % uncertainty interval , 1.86–2.23 million ) and women ( 1.29 million years of potential life Output:	Compared to other antiarrhythmics ( four studies , 839 participants ) amiodarone appeared to increase the risk of SCD ( RR 1.40 ; 95 % CI 0.56 to 3.52 ; very low quality of evidence ) , but there was no effect in all-cause mortality ( RR 1.03 ; 95 % CI 0.75 to 1.42 ; low quality evidence ) .Amiodarone was associated with an increase in pulmonary and thyroid adverse events . AUTHORS ' CONCLUSIONS There is low to moderate quality evidence that amiodarone reduces SCD , cardiac and all-cause mortality when compared to placebo or no intervention for primary prevention , and its effects are superior to other antiarrhythmics .
MS2999	*TASK* the task is to summarize an input biomedical literature in six sentences *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 influence of diurnal variations of mood ( DVM ) and sleep disturbances on treatment response was investigated in 42 patients with major depressive disorder ( not SAD ) under the treatment of either bright white light ( 2,500 lx ) or dim red light ( 50 lx ) . We found only a slight influence in certain subscales of DVM and no influence of sleep disturbances . These results are discussed under a clinical point of view and with respect to phase shift theories of depressive disorders In a group of 17 patients with non-SAD depressive disorders we compared the response of bipolar spectrum versus unipolar patients to treatment with light therapy . The main hypothesis was that bipolar spectrum depressed patients would preferentially respond to bright light therapy as compared to unipolar depressed patients . All patients were treated with either 400 or 2500 lux phototherapy for 2 h on seven consecutive days . All outcome measures , which included the SIGH-SAD , CGI , and the Anxiety and Depressive Factors of the SCL-90 , showed significant improvement in the bipolar vs. the unipolar spectrum patients . Unexpected this occurred regardless of the intensity of the light . These changes were judged to be quite clinical ly significant . All patients showing response were noted to have maintained their response at a 3-month follow-up Patients with recurrent winter depression and its subsyndromal form have been reported to benefit from bright full-spectrum light ( phototherapy ) . In order to determine whether this treatment ( 2 h in the morning ) during winter is effective in a r and om sample of the general population we investigated the responses of 20 subjects with varying degrees of winter difficulties . A control group ( n = 20 ) matched for the degree of seasonality , age , and sex was treated with dim light . Individuals were selected from a larger survey sample of the Montgomery County population ( MD , U.S.A. ) and were comparable to the latter in their degree of winter difficulties . Enhancement of environmental light does not , on the basis of the present study , appear to be indicated for the public at large , but rather for a subgroup of individuals with histories of winter difficulties Light therapy ( LT ) is regarded as the treatment of choice for seasonal affective disorder ( SAD ) . In nonseasonal depression the results of light therapy are nonconclusive . Sleep deprivation ( SD ) , however , is effective in 50 - 60 % of the patients with major depression . The predictive value of Total Sleep Deprivation ( TSD ) for the treatment outcome of antidepressiva has been already examined . Purpose of the present study was to test whether light therapy is more beneficial in TSD responders than in TSD nonresponders . 40 in patients with major depressive disorder completed one night of TSD . Twenty TSD responders and 20 TSD nonresponders were r and omly assigned to 14 days of bright light therapy ( 2500 lux , 7 - 9 a.m. ) or 14 days of dim light therapy ( red light 50 lux , 7 - 9 a.m. ) . Manova with repeated measurements revealed a significant difference in the course of depression over the time between TSD responders and nonresponders , but no significant difference between bright and dim light . Questions of placebo effect , of SAD and of personality variables as predictors of response to SD and LT are being discussed Phototherapy is regularly used in the treatment of seasonal affective disorder . There is evidence that it is also useful in the treatment of non‐seasonal depression , but relevant controlled experiments are difficult to design . In this study we r and omly assigned depressed in‐ patients to high and low levels of artificial light , the high levels exceeding those most commonly used in earlier reported trials . Both unipolar and bipolar depressions responded when phototherapy was used as an adjunct to pharmacotherapy , and mood improvement was related to the intensity of illumination , that is , patients treated with high levels of illumination improved significantly more than those who received low levels ( P < 0.02 ) . Our findings suggest that light therapy is generally applicable to depressive illnesses , and that the light intensities commonly used are suboptimal The data of the Berlin light therapy study were systematic ally reinvestigated for side-effects of light therapy as described in the literature . Forty-two patients with major depressive disorder ( RDC ) , who also met the criteria of ICD-9 ( 296.1 and 296.3 ) , were included . Patients were either given bright white-light treatment ( 2,500 lux ) or dim red-light treatment ( 50 lux ) from 7.20 a.m. to 9.20 a.m. every morning for a period of seven days . The study did not reveal any differences in side-effects between the two treatments . The results are discussed in relation to the two different treatment conditions The effects of two non-drug treatments ( physical exercise and bright light ) on mood , body weight and oxygen consumption were compared in age-matched groups of female subjects with winter depression , non-seasonal depression or without depression . It was found that oxygen consumption in the pre-treatment condition was similar in non-depressed subjects ( n=18 ) and depressed non-seasonals ( n=18 ) , while comparatively lower values were obtained in winter depression ( n=27 ) . Neither mood nor metabolic parameters changed significantly in the group of nine untreated winter depressives . One week of physical exercise ( 1-h pedaling on a bicycle ergometer between 13.00 and 14.00 h ) increased oxygen consumption in the group of nine winter depressives and lowered oxygen consumption in nine-subject groups of depressed and non-depressed non-seasonals . One week of bright light treatment ( 2-h exposure to 2500 lux between 14.00 and 16.00 h ) increased oxygen consumption in nine winter depressives and nine non-depressed subjects , while no significant change in oxygen consumption was found in nine subjects with non-seasonal depression . Weight loss was observed in the groups treated with physical exercise and in the group of light-treated winter depressives . Winter depression responded equally well to exercising and light , while a significant therapeutic difference in favor of exercising was found in non-seasonal depression . Overall , the results of the study suggest that energy-regulating systems are implicated in the antidepressant action of the non-drug treatments The clinical usefulness of total sleep deprivation ( TSD ) in the treatment of bipolar depression is hampered by a high-rate short-term relapse . Previous literature has suggested that both long-term lithium treatment and light therapy could successfully prevent relapse . We r and omized 115 bipolar depressed in patients to receive three cycles of TSD , alone or in combination with morning light exposure , given at an intensity of 150 or 2500 lux . Forty-nine patients were undergoing long-term treatment with lithium salts ( at least 6 months ) , while 66 patients were taking no psychotropic medication . Mood was self-rated by the Visual Analogue Scale three times a day during treatment . The results showed that both light therapy and ongoing lithium treatment significantly enhanced the effects of TSD on the perceived mood , with no additional benefit when the two treatments were combined . Subjective sleepiness during TSD , as rated by the self-administered Stanford Sleepiness Scale , was significantly reduced by light exposure , and was correlated with the outcome . This study confirms the possibility of obtaining a sustained antidepressant response to TSD in bipolar patients In previous research , the therapeutic effect of bright white light for so so-called seasonal affective disorder was clearly confirmed . The aim of the present study was to evaluate possible beneficial effects of bright white light in non-seasonal depression . 30 patients fulfilling RDC- criteria for major depressive disorder were r and omly assigned to a 7 day exposure from 7.20 to 9.20 a.m. The degree of illness was ascertained both objective ly with observer rating scales ( Hamilton Depression Scale , AMDP-system ) and through self-rating scales ( Complaint List and Depression Scale by von Zerssen ) . No difference was noted between bright light and dim light though a significant reduction of depressive symptomatology was observed for all patients during the treatment . These results were consistent for both observer rating and self-rating . In conclusion , bright white light has no superior effect as compared to dim light exposure in non-seasonal depression INTRODUCTION The aim of a double-blind study was to assess the efficacy of bright light therapy and /or imipramine in the treatment of in patients suffering with recurrent non-seasonal major depressive disorder . METHOD 34 in- patients with DSM-III-R diagnosis of major depressive disorder , recurrent type , were r and omly allocated into 3 treatment groups . After 4-day washout period with baseline assessment they underwent 3 weeks of different types of treatment : a ) Group A : bright light therapy ( 5000 lux from 6 - 8 a.m. ) and imipramine 150 mg/day . b ) Group B : bright light therapy ( 5000 lux from 6 - 8 a.m. ) and imipramine-like placebo . c ) Group C : dim red light ( 500 lux from 6 - 8 a.m. ) and imipramine 150 mg/day . Outcome measures included weekly Hamilton Psychiatric Rating Scale for Depression , Clinical Global Impression Scale , Montgomery and Asberg Psychiatric Rating Scale for Depression and Beck Depression Inventory . RESULTS Patients of all three groups improved significantly . The improvement of the patients of group B treated with bright light therapy plus placebo was superior to the other two groups , but not significantly . CONCLUSION Bright light therapy can be effective in the treatment of non-seasonal major depressive disorder Light therapy ( bright or dim light ) was given at different times ( morning or evening ) to 27 unmedicated patients with nonseasonal depression ( according to DSM-III-R criteria ) and 16 normal volunteers . Circadian rhythms in body temperature were measured before and after light therapy . Bright light significantly improved clinical symptoms of depression , as measured by the Hamilton Rating Scale for Depression ( HRSD ) , independent of the time of phototherapy . Dim light therapy had no effect on HRSD scores . Circadian rhythms of body temperatures in patients with affective disorder were more sensitive to the entraining effects of bright light than those of normal subjects , but these effects were not related to clinical improvement . Bright light exposure has an antidepressant effect on patients with nonseasonal depression , but the effect is unlikely to be mediated via the same circadian system that regulates body temperature OBJECTIVE About 5 % of pregnant women meet criteria for major depression . No pharmacotherapy is specifically approved for antepartum depression ; novel treatment approaches may be welcome . The authors explored the use of morning bright light therapy for antepartum depression . METHOD An open trial of bright light therapy in an A-B-A design was conducted for 3 - 5 weeks in 16 pregnant patients with major depression . The Hamilton Depression Rating Scale , Seasonal Affective Disorders Version , was administered to assess changes in mood . A follow-up question naire was used to assess outcome after delivery . RESULTS After 3 weeks of treatment , mean depression ratings improved by 49 % . Benefits were seen through 5 weeks of treatment . There was no evidence of adverse effects of light therapy on pregnancy . CONCLUSIONS These data provide evidence that morning light therapy has an antidepressant effect during pregnancy . A r and omized controlled trial is warranted to test this alternative to medication Inpatient studies have suggested that bright light therapy can be used to sustain the antidepressant effects of wake therapy ( sleep deprivation ) . In an outpatient trial , a half night of home wake treatment was followed by 1 week of light treatment . All subjects had Major Depressive Disorders according to DSM-IV criteria and were receiving concomitant antidepressant medication . Subjects were r and omly assigned to receive either 10,000 lux bright white light for 30 min between 6 and 9 AM or dim red ( placebo ) light at a comparable time . Seven subjects completed treatment with bright white light and six completed treatment with placebo . On the Hamilton Depression Rating Scale ( HDRS17 , SIGH-SAD-SR version ) , the group receiving bright light improved 27 % in 1 week ( P=0.002 ) . The group receiving placebo did not improve , except for one outlier . The benefit of bright light was significant compared to placebo with removal of the outlier ( P<0.025 ) Antidepressant and energizing effects of bright light exposure ( phototherapy ) have been widely reported to occur in patients with seasonal affective disorder . We have attempted to evaluate whether other segments of the population might benefit from phototherapy , most notably individuals with subsyndromal seasonal affective disorder , as well as healthy individuals with no winter difficulties ( controls ) . We have studied 20 subjects in each of these two categories and have found that bright artificial light did not alter mood and behavior in controls . In contrast , individuals with subsyndromal seasonal affective disorder responded favorably to treatment with bright environmental light . A dose of 5 hours of bright light exposure , divided between morning and evening , was more effective than 2 hours of exposure . This finding may have practical implication s for establishing optimal environmental lighting conditions for those individuals whose winter difficulties do not meet criteria for seasonal affective disorder BACKGROUND Using bright light for treating major depressive disorders which are not seasonal needs re assessment . METHODS Clinical trials of light treatment for nonseasonal major depressive disorders were compared with selected trials of light treatment of winter depression and with antidepressant clinical drug trials . RESULTS Light treatment of nonseasonal depression produces net benefits in the range of 12 - 35 % , often within 1 week . CONCLUSIONS Light 's value for nonseasonal and seasonal depression are comparable . Light appears to produce faster antidepressant benefits than psychopharmacologic treatment . LIMITATIONS Direct r and omizing comparisons between light and medications for nonseasonal Output:	In general , the quality of reporting was poor , and many review s did not report adverse effects systematic ally . The treatment response in the bright light group was better than in the control treatment group , but did not reach statistical significance . Treatment REVIEW ERS ' CONCLUSIONS For patients suffering from non-seasonal depression , bright light therapy offers modest though promising antidepressive efficacy , especially when administered during the first week of treatment , in the morning , and as an adjunctive treatment to sleep deprivation responders .

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