***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***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 responsiveness and minimal important change ( MIC ) of Evaluation of Ankylosing Spondylitis Quality of Life ( EASi-QoL ) , a reliable and valid patient-reported measure of AS-specific quality of life with four domains : physical function ( PF ) , disease activity ( DA ) , emotional well-being ( EWB ) and social participation ( SP ) . METHODS A total of 1000 UK AS patients received a postal question naire including EASi-QoL. Comparative responsiveness of EASi-QoL was assessed against measures reflecting similar health domains in patients self-reporting an improvement in their AS-specific health at 6 months on a health transition question . Effect size ( ES ) statistics were calculated for all measures and MIC was determined for EASi-QoL. Comparative responsiveness was determined in a r and omized trial of AS patients receiving etanercept ( ETN ) 50 mg weekly or SSZ 3 g daily . RESULTS Of 470 patients , 80 responding at 6 months reported health improvement . Responsiveness ( ES ) for EASi-QoL domains was superior or similar to comparator measures : DA 0.72 vs BASDAI 0.58 ; SP 0.52 vs SF-36 social functioning 0.29 ; PF 0.32 vs BASFI 0.28 and SF-36 PF 0.24 ; EWB 0.40 vs HADS-anxiety 0.13 , HADS-depression 0.21 and SF-36 mental health 0.35 . ES for the ASQoL was 0.40 . Superior ES was seen in those improving somewhat . In the r and omized trial , all EASi-QoL domains had superior responsiveness to comparator measures following ETN treatment . Following SSZ treatment , all EASi-QoL domains were highly responsive , but BASDAI and BASFI was more responsive than EASi-QoL(DA ) and ( PF ) , respectively . CONCLUSION In patients reporting improvement during routine clinical practice or following treatment with ETN or SSZ , EASi-QoL domains have superior or comparable responsiveness than comparable measures Background Patient reported outcomes ( PROs ) are especially useful in assessing treatments for rheumatoid arthritis ( RA ) since they measure dimensions of health-related quality of life that can not be captured using strictly objective physiological measures . The aim of this study was to compare the effects of combination etanercept and methotrexate ( ETN + MTX ) versus combination synthetic disease modifying antirheumatic drugs ( DMARDs ) and methotrexate ( DMARD + MTX ) on PRO measures among RA patients from the Asia-Pacific region , a population not widely studied to date . Patients with established moderate to severe rheumatoid arthritis who had an inadequate response to methotrexate  were studied . Methods Patients were r and omized to either ETN + MTX ( N = 197 ) or DMARD + MTX ( N = 103 ) in an open-label , active-comparator , multicenter study , with PRO measures design ed as prospect i ve secondary endpoints . The Health Assessment Question naire ( HAQ ) , Functional Assessment of Chronic Illness Therapy Fatigue Scale ( FACIT-Fatigue ) , Medical Outcomes Short Form-36 Health Survey ( SF-36 ) , Hospital Anxiety and Depression Scale ( HADS ) and the Work Productivity and Activity Impairment Question naire : General Health ( WPAI : GH ) were used . Results Significantly greater improvements were noted for the ETN + MTX group at week16 for HAQ mean scores and for proportion of patients achieving HAQ score ≤ 0.5 , compared to patients in the DMARD + MTX group . SF-36 Summary Scores for physical and mental components and for 6 of 8 health domains showed significantly greater improvements at week16 for the ETN + MTX group ; only scores for physical functioning and role-emotional domains did not differ significantly between the two treatment arms . Greater improvements at week16 were noted for the ETN + MTX group for FACIT-Fatigue , HADS , and WPAI : GH mean scores . Conclusion Combination therapy using ETN + MTX demonstrated superior improvements using a comprehensive set of PRO measures , compared to combination therapy with usual st and ard of care DMARDs plus MTX  in patients with established rheumatoid arthritis from the Asia-Pacific region . Trial registration clintrials.gov # & NA ; Psychological and social factors have been shown , separately , to predict outcome in individuals with chronic low back pain . Few previous studies , however , have integrated both psychological and social factors , using prospect i ve study of clinic population s of low back pain patients , to identify which are the most important targets for treatment . One hundred and eight patients with chronic low back pain , newly referred to an orthopaedic outpatient clinic , completed assessment s of  demographic characteristics , details of back pain , measures of anxiety and depression ( Hospital Anxiety and Depression Scale , HADS ) , fearful beliefs about pain ( Fear Avoidance Beliefs Question naire ) , social stresses ( Life Events and Difficulties Schedule ) and physical aspects of health‐related quality of life [ SF‐36 Physical Component summary Score scale ( PCS ) ] . Six months later subjects completed the SF‐36 PCS and the number of healthcare contacts during follow‐up was recorded . Independent predictors of SF‐36 PCS at 6‐month follow‐up were duration of pain [ ( st and ardised regression coefficient ( β ) = −0.18 , p = 0.04 ) , HADS score ( β ) = −0.27 , p = 0.003 ] and back pain related social difficulties ( β = −0.42 , p < 0.0005 ) . Number of healthcare contacts over the 6 months ranged from 1 to 29 , and was independently predicted by perceived cause of pain [ Incident Rate Ratio ( IRR ) = 1.46 , p = 0.03 ] , Fear Avoidance Beliefs about work ( IRR = 1.02 , p = 0.009 ) and back pain related social difficulties ( IRR = 1.16 , p = 0.03 ) . To conclude , anxiety , depression , fear avoidance beliefs relating to work and back pain related stresses predict impairment in subsequent physical health‐related quality of life and number of healthcare contacts . Interventions targeting these psychosocial variables in clinic patients may lead to improved quality of life and healthcare costs BACKGROUND Infectious , autoimmune , and neurodegenerative diseases are associated with profound psychological disturbances . Studies in animals clearly demonstrate that cytokines mediate illness-associated behavioral changes . However , the mechanisms underlying the respective psychological alterations in humans have not been established yet . Therefore , we investigated the effects of low-dose endotoxemia , a well-established and safe model of host-defense activation , on emotional , cognitive , immunological , and endocrine parameters . METHODS In a double-blind , crossover study , 20 healthy male volunteers completed psychological question naires and neuropsychological tests 1 , 3 , and 9 hours after intravenous injection of Salmonella abortus equi endotoxin ( 0.8 ng/kg ) or saline in 2 experimental sessions . Blood sample s were collected hourly , and rectal temperature and heart rate were monitored continuously . RESULTS Endotoxin had no effects on physical sickness symptoms , blood pressure , or heart rate . Endotoxin caused a mild increase in rectal temperature ( 0.5 degrees C ) , and increased the circulating levels of tumor necrosis factor alpha ( TNF-alpha ) , soluble TNF receptors , interleukin (IL)-6 , IL-1 receptor antagonist , and cortisol . After endotoxin administration , the subjects showed a transient significant increase in the levels of anxiety ( effect size [ ES ] = 0.55 ) and depressed mood ( ES = 0.66 ) . Verbal and nonverbal memory functions were significantly decreased ( ES = 0.55 to 0.64 ) . Significant positive correlations were found between cytokine secretion and endotoxin-induced anxiety ( r = 0.49 to r = 0.60 ) , depressed mood ( r = 0.40 to r = 0.75 ) , and decreases in memory performance ( r = 0.46 to r = 0.68 ) . CONCLUSIONS In humans , a mild stimulation of the primary host defense has negative effects on emotional and memory functions , which are probably caused by cytokine release . Hence , cytokines represent a novel target for neuropsychopharmacological research CONTEXT Increased concentrations of inflammatory biomarkers predict antidepressant nonresponse , and inflammatory cytokines can sabotage and circumvent the mechanisms of action of conventional antidepressants . OBJECTIVES To determine whether inhibition of the inflammatory cytokine tumor necrosis factor ( TNF ) reduces depressive symptoms in patients with treatment-resistant depression and whether an increase in baseline plasma inflammatory biomarkers , including high-sensitivity C-reactive protein ( hs-CRP ) , TNF , and its soluble receptors , predicts treatment response . DESIGN Double-blind , placebo-controlled , r and omized clinical trial . SETTING Outpatient infusion center at Emory University in Atlanta , Georgia . PARTICIPANTS A total of 60 medically stable out patients with major depression who were either on a consistent antidepressant regimen ( n = 37 ) or medication-free ( n = 23 ) for 4 weeks or more and who were moderately resistant to treatment as determined by the Massachusetts General Hospital Staging method . INTERVENTIONS Three infusions of the TNF antagonist infliximab ( 5 mg/kg ) ( n = 30 ) or placebo ( n = 30 ) at baseline and weeks 2 and 6 of a 12-week trial . MAIN OUTCOME MEASURES The 17-item Hamilton Scale for Depression ( HAM-D ) scores . RESULTS No overall difference in change of HAM-D scores between treatment groups across time was found . However , there was a significant interaction between treatment , time , and log baseline hs-CRP concentration ( P = .01 ) , with change in HAM-D scores ( baseline to week 12 ) favoring infliximab-treated patients at a baseline hs-CRP concentration greater than 5 mg/L and favoring placebo-treated patients at a baseline hs-CRP concentration of 5 mg/L or less . Exploratory analyses focusing on patients with a baseline hs-CRP concentration greater than 5 mg/L revealed a treatment response ( ≥50 % reduction in HAM-D score at any point during treatment ) of 62 % ( 8 of 13 patients ) in infliximab-treated patients vs 33 % ( 3 of 9 patients ) in placebo-treated patients ( P = .19 ) . Baseline concentrations of TNF and its soluble receptors were significantly higher in infliximab-treated responders vs nonresponders ( P < .05 ) , and infliximab-treated responders exhibited significantly greater decreases in hs-CRP from baseline to week 12 compared with placebo-treated responders ( P < .01 ) . Dropouts and adverse events were limited and did not differ between groups . CONCLUSIONS This proof-of-concept study suggests that TNF antagonism does not have generalized efficacy in treatment-resistant depression but may improve depressive symptoms in patients with high baseline inflammatory biomarkers . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00463580 Objective The aim of this study was to assess the effect of infliximab on quality of life in patients with active Crohn 's disease ( CD ) inadequately responsive to concomitant therapies . Methods We examined responses to the Inflammatory Bowel Disease Question naire ( IBDQ ) from patients enrolled in a previously reported , r and omized , placebo-controlled study . Patients with active CD received a single intravenous infusion of either placebo or infliximab 5 , 10 , or 20 mg/kg . Most patients received stable doses of mesalamine , corticosteroids , azathioprine , or 6-mercaptopurine throughout the study . Changes from baseline in overall IBDQ score and individual dimensions at 4 weeks postinfusion were compared . Results Patients treated with infliximab had a significantly larger improvement in overall IBDQ score than those treated with placebo at 4 weeks ( p < 0.001 ) . Infliximab-treated patients also had larger improvements in all IBDQ dimensions : bowel ( p = 0.007 ) , social ( p = 0.002 ) , emotional ( p < 0.001 ) , and systemic ( p < 0.001 ) . A significantly larger proportion of infliximab-treated patients reported having normal or near-normal frequency of bowel movements in the past week ( p < 0.001 ) , full or a lot of energy ( p = 0.019 ) , and no or hardly any difficulty doing leisure or sports activities ( p = 0.011 ) , and being extremely or very satisfied with their personal life ( p = 0.046 ) . They also significantly differed in responses regarding fatigue , frustration , ability to work , general well-being , depression , anxiety , and anger result ing from bowel problems . Conclusions These results indicate that infliximab significantly improved quality of life in patients with active CD , increasing their ability to work and participate in leisure activities , and decreasing feelings of fatigue , depression , and anger OBJECTIVE The purpose of this study was to assess the impact of baseline A1c , cardiovascular disease , and depression on subsequent health care costs 
    Output:
    
TNF-α inhibitor therapy  reduces depression in people with chronic disease though the effects are small .