***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***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 spite of current therapies , the overall health status of patients with SLE is poor . High-dose cyclophosphamide ( 50 mg/kg for 4 days ) with or without stem-cell rescue has been introduced as a new therapy for severe SLE , including renal and central nervous system (CNS)-SLE . Long-term durable responses have been found to be 40 % . A r and omised clinical trial was completed comparing high-dose cyclophosphamide with monthly intravenous cyclophosphamide ( 750 mg/m squared bovine serum albumin ) in patients with SLE who need cyclophosphamide for the first time . The primary outcome of the trial was complete clinical response . In this report , we compare the treatment groups with respect to quality of life .  The patients in this study had a mean age of 35.3 ± 10.1 years , were of Caucasian ( 35 % ) , African-American ( 51 % ) , Hispanic ( 8 % ) and Asian ( 6 % ) people , and 88 % were women . The organ leading to treatment was renal lupus in 29 % , CNS-lupus in 45 % and other organs in 26 % . Quality of life was measured at each visit using the Medical Outcome Study Short-Form 36 ( SF-36 ) . At 6 months , the patients in the high-dose cyclophosphamide trial arm had significantly greater improvement than patients in the monthly intravenous cyclophosphamide arm ( P = 0.026 ; P = 0.0082 , respectively ) in the categories of general health and social functioning . At 18 months , the improvement in the role-physical score was significantly greater in the high-dose cyclophosphamide trial arm than in the monthly-dose cyclophosphamide arm ( P = 0.025 ) . At the end of the two and a half-year study , there were no significant differences between the groups with respect to changes in SF-36 . By pooling the groups , at 30 months , there was a statistically significant ( P < 0.05 ) improvement over baseline in 6 of the 8 SF-36 domains . This study shows earlier improvement in SF-36 measures at 6 months in the high-dose cyclophosphamide group but equal improvement in both arms at two and one and a half years . Eventual improvements in quality -of-life with both cyclophosphamide regimens are clinical ly meaningful to both patients and treating physicians Objective . To evaluate health-related quality of life ( HRQOL ) and corticosteroid use in patients with moderate to severely active SLE enrolled in two international , multicentre , r and omized controlled trials of epratuzumab ( ALLEVIATE-1 and -2 ) and a long-term extension study ( SL0006 ) . Methods . Ninety ALLEVIATE patients ( 43 % BILAG A , mean BILAG score 13.2 ) were r and omized to receive 360 mg/m2 ( n = 42 ) or 720 mg/m2 ( n = 11 ) epratuzumab or placebo ( n = 37 ) , plus st and ard of care , in 12-week cycles . Corticosteroid use , patient and physician global assessment s of disease activity ( PtGA and PGA ) and 36-item Medical Outcomes Survey Short Form ( SF-36 ) results were recorded at baseline and every 4 weeks . Both trials were prematurely discontinued due to a drug supply interruption ; patients followed for ≥6 months were analysed . Twenty-nine patients continued in SL0006 , with interim analysis at a median exposure of 120 ( range 13–184 ) weeks . Results . At week 12 , proportions of patients with a PGA ≥20 % above baseline or with a PtGA improvement greater than or equal to the minimum clinical ly important difference were higher in the epratuzumab arms than the placebo arm . PGA and PtGA improvements were sustained but did not reach statistical significance . At week 24 , mean cumulative corticosteroid doses  with epratuzumab 360 and 720 mg/m2 were 1051 and 1973 mg less than placebo ( P = 0.034 and 0.081 , respectively ) . At week 48 , SF-36 scores approached or exceeded US age- and gender-matched norms in five domains with the 360 mg/m2 treatment . Improvements were maintained in SL0006 over ∼2 years . Conclusion . Epratuzumab treatment produced clinical ly meaningful and sustained improvements in PGA , PtGA and HRQOL and reductions in corticosteroid doses 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 Objectives The aim was to evaluate the cross-cultural validity of the Lupus Impact Tracker ( LIT ) in five European countries and to assess its acceptability and feasibility from the patient and physician perspectives . Methods A prospect i ve , observational , cross-sectional and multicentre validation study was conducted in clinical setting s. Before the visit , patients completed LIT , Short Form 36 ( SF-36 ) and care satisfaction question naires . During the visit , physicians assessed disease activity [ Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI ] , organ damage [ SLICC/ACR damage index ( SDI ) ] and flare occurrence . Cross-cultural validity was assessed using the Differential Item Functioning method . Results Five hundred and sixty-nine SLE patients were included by 25 specialists ; 91.7 % were out patients and 89.9 % female , with mean age 43.5 ( 13.0 ) years . Disease profile was as follows : 18.3 % experienced flares ; mean SELENA-SLEDAI score 3.4 ( 4.5 ) ; mean SDI score 0.8 ( 1.4 ) ; and SF-36 mean physical and mental component summary scores : physical component summary 42.8 ( 10.8 ) and mental component summary 43.0 ( 12.3 ) . Mean LIT score was 34.2 ( 22.3 ) ( median : 32.5 ) , indicating that lupus moderately impacted patients ' daily life . A cultural Differential Item Functioning of negligible magnitude was detected across countries ( pseudo- R 2 difference of 0.01 - 0.04 ) . Differences were observed between LIT scores and Physician Global Assessment , SELENA-SLEDAI , SDI scores = 0 ( P < 0.035 ) and absence of flares ( P = 0.004 ) . The LIT showed a strong association with SF-36 physical and social role functioning , vitality , bodily pain and mental health ( P < 0.001 ) . The LIT was well accepted by patients and physicians . It was reliable , with Cronbach α coefficients ranging from 0.89 to 0.92 among countries . Conclusion The LIT is vali date d in the five participating European countries . The results show its reliability and cultural invariability across countries . They suggest that LIT can be used in routine clinical practice to evaluate and follow patient-reported outcomes in order to improve patient-physician interaction Introduction A recent metabolomic screen of sera from patients with Systemic Lupus Erythematosus ( SLE ) found reduction of antioxidants and substrates for energy generation . These metabolic alterations may underlie one of the most common features of SLE - fatigue . The metabolomic studies also noted reduced omega-3 fatty acids , which are powerful anti- oxidants . This deficiency may be causally related to oxidative stress , inflammation , disease activity , and fatigue in SLE . Supplementation of omega-3 fatty acids using fish oil in SLE has been shown to reduce oxidative stress in other studies . The objective of this study is to evaluate the effect of fish oil supplementation on clinical measures of fatigue , quality of life , and disease activity as part of a r and omized clinical trial . Methods Fifty SLE patients recruited in outpatient clinics were r and omized 1:1 to fish oil supplementation or olive oil placebo , and blinded to their treatment group . At baseline and after 6 months of treatment , R AND Short Form-36 ( R AND SF-36 ) , Fatigue Severity Scale ( FSS ) , SLE Disease Activity Index ( SLEDAI ) , and Physician Global Assessment ( PGA ) were completed ; serum was also collected for soluble mediator analysis . Results Thirty-two patients completed the study .  PGA improved significantly in the fish oil group compared with the placebo group ( p = 0.015 ) . The R AND SF-36 Energy/fatigue and Emotional well-being scores demonstrated improvement trends ( p = 0.092 and 0.070 ) . No clear difference was seen in FSS and SLEDAI ( p = 0.350 and p = 0.417 ) . Erythrocyte sedimentation rate and serum IL-12 were reduced ( p = 0.008 and p = 0.058 ) ; while serum IL-13 was increased by fish oil supplementation ( p = 0.033 ) . Conclusions In this r and omized , placebo-controlled 6-month trial , SLE patients r and omized to fish oil supplementation demonstrated improvement in their PGA , R AND SF-36 , and some circulating inflammatory markers . Trial registration Clinical Trials.gov Identifier : NCT02021513 ( registered 13 December 2013 ) Introduction This trial evaluated the safety , biologic activity , and pharmacokinetics of belimumab , a fully human monoclonal antibody that inhibits the biologic activity of the soluble form of the essential B-cell survival factor B-lymphocyte stimulator ( BLyS ) in patients with systemic lupus erythematosus ( SLE ) . Methods Seventy patients with mild-to-moderate SLE were enrolled in a phase I , double-blind , r and omized study and treated with placebo ( n = 13 ) or belimumab ( n = 57 ) at four different doses ( 1.0 , 4.0 , 10 , and 20 mg/kg ) as a single infusion or two infusions 21 days apart . Patients were followed for 84 to 105 days to assess adverse events , pharmacokinetics , peripheral blood B-cell counts , serology , and SLE disease activity . Data from the study were summarized using descriptive statistics . χ2 type tests were used to analyze discrete variables . The Kruskal-Wallis test , the Wilcoxon test , and the analysis of covariance were used to analyze the continuous variables , as appropriate . The analysis was performed on all r and omized patients who received study agent . Results The incidences of adverse events and laboratory abnormalities were similar among the belimumab and placebo groups . Belimumab pharmacokinetics were linear across the 1.0 to 20 mg/kg dose range . Long terminal elimination half-life ( 8.5 to 14.1 days ) , slow clearance ( 7 ml/day per kg ) , and small volume of distribution ( 69 to 112 ml/kg ) were consistent with a fully human antibody . Significant reductions in median percentages of CD20 + B cells were observed in patients treated with a single dose of belimumab versus placebo ( day 42 : P = 0.0042 ; and day 84 : P = 0.0036 ) and in patients treated with two doses of belimumab versus placebo ( day 105 : P = 0.0305 ) . SLE disease activity did not change after one or two doses of belimumab . Conclusions Belimumab was well tolerated and reduced peripheral B-cell levels in SLE patients . These data support further studies of belimumab in autoimmune disorders . Trial Registration NCT0 
    Output:
    
All measures had good convergent and discriminant validity .
PROMIS provided the strongest evidence for known-group validity and reliability among generic instruments ; however , data on its responsiveness have not been published .
Across measures , st and ardised response means were generally indicative of poor-moderate sensitivity to longitudinal change .
In RCTs , clinical ly important improvements were reported in SF36 scores from baseline ; however , between-arm differences were frequently non-significant and non-important .
SF36 , PROMIS , LupusQoL and LIT had the strongest evidence for acceptable measurement properties , but few measures aside from the SF36 have been incorporated into clinical trials .