***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Objective To examine the prevalence of outcome reporting bias — the selection for publication of a subset of the original recorded outcome variables on the basis of the results — and its impact on Cochrane review s. Design A nine point classification system for missing outcome data in r and omised trials was developed and applied to the trials assessed in a large , unselected cohort of Cochrane systematic review s. Research ers who conducted the trials were contacted and the reason sought for the non-reporting of data . A sensitivity analysis was undertaken to assess the impact of outcome reporting bias on review s that included a single meta- analysis of the review primary outcome . Results More than half ( 157/283 ( 55 % ) ) the review s did not include full data for the review primary outcome of interest from all eligible trials . The median amount of review outcome data missing for any reason was 10 % , whereas 50 % or more of the potential data were missing in 70 ( 25 % ) review s. It was clear from the publications for 155 ( 6 % ) of the 2486 assessable trials that the research ers had measured and analysed the review primary outcome but did not report or only partially reported the results . For reports that did not mention the review primary outcome , our classification regarding the presence of outcome reporting bias was shown to have a sensitivity of 88 % ( 95 % CI 65 % to 100 % ) and specificity of 80 % ( 95 % CI 69 % to 90 % ) on the basis of responses from 62 trialists . A third of Cochrane review s ( 96/283 ( 34 % ) ) contained at least one trial with high suspicion of outcome reporting bias for the review primary outcome . In a sensitivity analysis undertaken for 81 review s with a single meta- analysis of the primary outcome of interest , the treatment effect estimate was reduced by 20 % or more in 19 ( 23 % ) . Of the 42 meta-analyses with a statistically significant result only , eight ( 19 % ) became non-significant after adjustment for outcome reporting bias and 11 ( 26 % ) would have overestimated the treatment effect by 20 % or more . Conclusions Outcome reporting bias is an under-recognised problem that affects the conclusions in a substantial proportion of Cochrane review s. Individuals conducting systematic review s need to address explicitly the issue of missing outcome data for their review to be considered a reliable source of evidence . Extra care is required during data extraction , review ers should identify when a trial reports that an outcome was measured but no results were reported or events observed , and contact with trialists should be encouraged PURPOSE The efficacy and safety of darbepoetin alpha ( DA ) for treating patients with active cancer and anemia not receiving or planning to receive cytotoxic chemotherapy or myelosuppressive radiotherapy was evaluated . PATIENTS AND METHODS Patients with active cancer and anemia not receiving or planning to receive chemotherapy or radiotherapy were enrolled onto a phase III , multicenter , r and omized , placebo-controlled study and administered placebo or DA 6.75 microg/kg every 4 weeks ( Q4W ) for up to 16 weeks with a 2-year follow-up for survival . Patients who completed 16 weeks of treatment could receive the same treatment as r and omized Q4W for an additional 16 weeks . The primary end point was all occurrences of transfusions from weeks 5 through 17 ; safety end points included incidence of adverse events and survival . RESULTS The incidence of transfusions between weeks 5 and 17 was lower in the DA group but was not statistically significantly different from that of placebo . DA was associated with an increased incidence of cardiovascular and thromboembolic events and more deaths during the initial 16-week treatment period . Long-term survival data demonstrated statistically significantly poorer survival in patients treated with DA versus placebo ( P = .022 ) . This effect varied by baseline covariates including , sex , tumor type , and geographic region ; statistical significance diminished ( P = .12 ) when the analysis was adjusted for baseline imbalances or known prognostic factors . CONCLUSION DA was not associated with a statistically significant reduction in transfusions . Shorter survival was observed in the DA arm ; thus , this study does not support the use of erythropoiesis-stimulating agents in this subset of patients with anemia of cancer 6007 Background : The study aim ed to evaluate if correction of low hemoglobin ( Hb ) levels by means of the erythropoietin stimulating agent : darbepoetin alpha ( Aranesp ) during radiotherapy ( RT ) improves outcome in patients with HNSCC . Following a planned interim analysis which showed inferiority of the experimental treatment , the trial was stopped in November 2006 . METHODS Pts with HNSCC eligible for primary RT alone and with Hb values below 14.0 g/dl were r and omized to receive Aranesp together with accelerated fractionated RT . Pts . were stratified according to gender , T and N staging , tumor site , and institution . Aranesp was given subcutaneously in a dose of 150 micrograms weekly during RT , or stopped earlier if the Hb exceeded 15.5 g/dl . RESULTS In total , 522 patients ( of a planned intake of 600 ) were included at the time of the interim analysis . Of these 514 pts were eligible for analysis ( 255 pts treated with Aranesp and 259 pts in the control group ) with a median follow up of 49 months . Among these , 201 developed a loco-regional failure ( primary endpoint ) . There have been 238 deaths of which 176 are due to HNSCC . The patients were evenly distributed according to the stratification parameters ( gender , T and N staging , tumor site , institution).Aranesp result ed in the expected increase in Hb in more than 81 % of the patients . The compliance to Aranesp was good with no significant difference in serious ( cardiovascular ) adverse events ( 3 % vs. 1 % ) . Overall , the results showed a poorer outcome in 5-year loco-regional control ( 59 % vs. 68 % ( p = 0.04 , RR : 1.47 [ 1.14 - 1.94 ] ) for the Aranesp vs. control arm . This was also seen for the endpoint of disease-free survival ( 37 % vs. 47 % , p = 0.02 , RR : 1.32 [ 1.04 - 1.68 ] ) , whereas there was no significant difference in overall survival ( 40 % vs. 51 % , p = 0.16 , RR : 1.20 [ 0.93 - 1.55 ] ) . There were no differences in radiation related morbidity . All univariate analyses were confirmed in a multivariate setting . CONCLUSIONS Correction of the Hb level with Aranesp in patients with HNSCC result ed in a significantly poorer tumor control after radiotherapy . The treatment principle was ab and oned and the difference in outcome is being subjected to further examination . No significant financial relationships to disclose BACKGROUND Anemia is common in cancer and has been associated with fatigue and reduced health-related quality of life ( HRQOL ) . We report the association between hemoglobin and fatigue and the impact of reducing fatigue on several domains of HRQOL . PATIENTS AND METHODS These analyses were based on five r and omized trials . Patients completed the Functional Assessment of Cancer Therapy ( FACT ) Anemia scales and numeric rating scales of Energy , Activity and Overall Health  at baseline and after the 12-week treatment period . t-tests and linear regression models were used to evaluate associations . Analyses were stratified into three groups : solid tumor chemotherapy patients , lymphoproliferative malignancy chemotherapy patients and non-chemotherapy patients . RESULTS Adjusted mean differences ( 95 % CI ) in FACT Fatigue change scores between hemoglobin responders ( > or = 2 g/dl increase ) and non-responders were 3.0 ( 1.2 , 4.7 ) , 2.8 ( 0.6 , 5.0 ) and 5.8 ( 2.2 , 9.5 ) among the solid tumor , lymphoproliferative malignancy and non-chemotherapy groups , respectively . Significantly greater improvements ( P < 0.01 ) were observed in the FACT well-being scales for patients with meaningful improvement in fatigue ( FACT Fatigue change score > or =3 points ) . After controlling for other factors , patients whose fatigue improved reported substantially greater improvements in energy , ability to perform usual activities and overall health ( P < 0.0001 ) . CONCLUSIONS Across five trials of cancer patients on and off chemotherapy , hemoglobin response was associated with meaningful improvements in fatigue , which , in turn , was associated with improved physical , functional , emotional and overall well-being A recent study in dogs suggested that erythropoietin ( EPO ) not only promotes the synthesis of increased numbers of reticulated platelets but that these newly produced platelets are hyperreactive compared with controls . Because of the increasing use of EPO in the perioperative setting , we characterized the effects of EPO on platelet reactivity in healthy human volunteers . In a r and omized , controlled trial , we studied the effects of EPO on platelet reactivity , thrombopoiesis , and endothelial activation in circumstances similar to those of autologous blood donation . Thirty healthy male volunteers received placebo or EPO ( 100 or 500 U/kg of body weight given intravenously ) three times a week for 2 weeks and underwent phlebotomy on days 8 and 15 . Thrombin receptor-activating peptide induced expression of P-selectin , and CD63 increased 2- to 3-fold during EPO treatment . The enhanced platelet reactivity was also reflected by a 50 % increase in soluble P-selectin in plasma . Plasma E-selectin levels increased in a dose-dependent fashion by more than 100 % during EPO treatment , indicating substantial activation of endothelial cells . A 10 % to 20 % increase in platelet counts was observed in both EPO groups on day 5 . In the placebo group , platelets increased only several days after the first phlebotomy . The increase in platelet counts was not reflected by changes in the amounts of reticulated platelets or circulating progenitor cells . In summary , we found that EPO markedly enhances endothelial activation and platelet reactivity , which may adversely affect patients at cardiovascular risk . However , the increased platelet reactivity could be exploited in patients with platelet dysfunction . ( Blood . 2000;95:2983 - 2989 BACKGROUND AND OBJECTIVES Continuous erythropoietin receptor activator ( C.E.R.A. ) is an innovative agent with unique erythropoietin receptor activity and a prolonged half-life , which has the potential for administration at extended dosing intervals . The objectives of this dose-finding study were to evaluate the hemoglobin ( Hb ) dose-response , pharmacokinetics , and safety of repeated doses of C.E.R.A. given once every 3 weeks to anemic patients with multiple myeloma ( MM ) receiving chemotherapy . DESIGN AND METHODS This was an exploratory two-stage , open-label , parallel-group , multicenter study . Patients received C.E.R.A. doses of 1.0 , 2.0 , 3.5 , 4.2 , 5.0 , 6.5 , or 8.0 mg/kg once every 3 weeks by subcutaneous injection initially for 6 weeks , followed by a 12-week optional extension period . The primary outcome measures were the average Hb level and its change from baseline over the initial 6-week period , based on values of the slope of the linear regression analysis and the area under the curve . Rates of Hb response ( defined as an increase in Hb of > or = 2 g/dL without transfusion ) and blood transfusion were also evaluated . RESULTS Sixty-four patients entered the study . Dose-related increases in Hb levels were observed during the initial 6-week treatment period for C.E.R.A. doses of 1.0 - 4.2 mg/kg , with a similar response observed at higher doses . At least 70 % of patients receiving 2.0 - 8.0 mg/kg of C.E.R.A. had Hb responses during the 18-week study . The elimination half-life of C.E.R.A. was found to be long ( 6.3 - 9.7 days [ 151.2 - 232.8 hours ] ) . All doses were generally well tolerated . INTERPRETATION AND CONCLUSIONS Based on its unique , long elimination half-life , C.E.R.A. has been demonstrated to be an effective and well-tolerated treatment of anemia given once every 3 weeks to patients with multiple myeloma receiving chemotherapy PURPOSE To determine the effect of darbepoetin alfa ( DA ) on progression-free survival ( PFS ) and overall survival ( OS ) in patients with chemotherapy-induced anemia ( CIA ) . PATIENTS AND METHODS Two 16-week r and omized , double-blind , placebo-controlled phase III studies of weekly DA in anemic patients with lung cancer ( n = 314 ) or lymphoproliferative malignancies ( LPMs ; n = 344 ) undergoing chemotherapy  were analyzed with prospect ively defined long-term PFS and OS end points . Short-term effects of DA on PFS and OS were analyzed by including two additional 16-week dose-finding , double-blind , placebo-controlled studies in anemic patients with multiple tumor types ( n = 405 ) and LPMs ( n = 66 ) . RESULTS Median follow-up is 15.8 months ( lung cancer ) and 32.6 months ( L 
    Output:
    
In addition , there is strong evidence that cancer patients receiving ESAs  have an increased risk of thromboembolic and cardiovascular events .