human
***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 Endogenous opioid peptides have been shown to play a role in the development and /or perpetuation of inflammation . We hypothesize that the endogenous opioid system is involved in inflammatory bowel disease , and antagonism of the opioid – opioid receptor will lead to reversal of inflammation . Aims A r and omized double-blind placebo-controlled study was design ed to test the efficacy and safety of an opioid antagonist for 12 weeks in adults with active Crohn ’s disease . Methods Forty subjects with active Crohn ’s disease were enrolled in the study . R and omized patients received daily oral administration of 4.5-mg naltrexone or placebo . Providers and patients were masked to treatment assignment . The primary outcome was the proportion of subjects in each arm with a 70-point decline in Crohn ’s Disease Activity Index score ( CDAI ) . The secondary outcome included mucosal healing based upon colonoscopy appearance and histology . Results Eighty-eight percent of those treated with naltrexone had at least a 70-point decline in CDAI scores compared to 40 % of placebo-treated patients ( p = 0.009 ) . After 12 weeks , 78 % of subjects treated with naltrexone exhibited an endoscopic response as indicated by a 5-point decline in the Crohn ’s disease endoscopy index severity score ( CDEIS ) from baseline compared to 28 % response in placebo-treated controls ( p = 0.008 ) , and 33 % achieved remission with a CDEIS score < 6 , whereas only 8 % of those on placebo showed the same change . Fatigue was the only side effect reported that was significantly greater in subjects receiving placebo . Conclusions Naltrexone improves clinical and inflammatory activity of subjects with moderate to severe Crohn ’s disease compared to placebo-treated controls . Strategies to alter the endogenous opioid system provide promise for the treatment of Crohn ’s disease AIM To study the effect of infliximab on fatigue in relation to cytokine levels in Crohn 's disease ( CD ) patients . METHODS Fourteen CD patients were blinded for treatment and received placebo at baseline , and infliximab 2 wk later , with a follow-up of 4 wk . Blood sample s were drawn on a regular basis , and question naires on fatigue , depression , quality of life , and clinical disease activity were completed at regular intervals . RESULTS After placebo infusion , fatigue scores decreased within 3 d ( 3.5 points + /- 1.1 , P < or= 0.01 ) , but returned to baseline values 14 d after this infusion . The drop of fatigue scores following infliximab infusion sustained until the end of the study ( 3.8 points + /- 1.4 , P < or= 0.05 ) . Quality of life was increased at the end of the study compared to baseline values ( 138.6 + /- 9.4 vs 179.4 + /- 6.7 ; P < or= 0.005 ) , whereas depression scores were decreased ( 20.4 + /- 9.4 vs 11.3 + /- 2.2 ; P < or= 0.01 ) . No correlation between the severity of fatigue and the level of cytokines was observed . CONCLUSION The reduction of fatigue after infliximab infusion is subjective to a placebo effect . The effect of infliximab on fatigue , however , persists while the placebo effect disappears after a short period of time . A clear role of cytokines could not be substantiated In this paper the psychometric properties of the multidimensional fatigue inventory ( MFI-20 ) are established further in cancer patients . The MFI is a 20-item self-report instrument design ed to measure fatigue . It covers the following dimensions : general fatigue , physical fatigue , reduced activity , reduced motivation and mental fatigue . The instrument was used in a Dutch and Scottish sample of cancer patients receiving radiotherapy .  The dimensional structure was assessed using confirmatory factor analyses ( Lisrel 's unweighted least-squares method ) . The hypothesised five-factor model appeared to fit the data in both sample s ( adjusted goodness of fit ; AGFI : 0.97 and 0.98 ) . Internal consistency of the separate scales was good in both the Dutch and Scottish sample s with Cronbach 's alpha coefficients ranging from 0.79 to 0.93 . Construct validity was assessed by correlating the MFI-20 to activities of daily living , anxiety and depression . Significant relations were assumed . Convergent validity was investigated by correlating the MFI scales with a visual analogue scale measuring fatigue and with a fatigue-scale derived from the Rotterdam Symptom Checklist . Results support the validity of the MFI-20 . The highly similar results in the Dutch and Scottish sample suggest that the portrayal of fatigue using the MFI-20 is quite robust Although inflammatory bowel disease ( IBD ) affects patients ' psychological well-being , previous educational programs have failed to demonstrate effects on psychosocial outcomes and quality of life . Therefore , we developed a group-based psychoeducational program that combined provision of both medical information and psychological self-management skills , delivered in an interactive manner , and evaluated it in a large , cluster-r and omized trial . We assigned 540 rehabilitation in patients suffering from IBD ( mean age 43 years , 66 % female ) to either the new intervention or a control group comprising the same overall intensity and the same medical information , but only general psychosocial information . The primary outcome was patient-reported IBD-related concerns . Secondary outcomes included disease knowledge , coping , self-management skills , fear of progression , anxiety , depression and quality of life . Assessment s took place at baseline , end of rehabilitation and after 3 and 12 months . The psychoeducational self-management program did not prove superior to the control group regarding primary and secondary outcomes . However , positive changes over time occurred in both groups regarding most outcomes . The superior effectiveness of the newly developed psychoeducational program could not be demonstrated . Since the intervention and control groups may have been too similar , this trial may have been too conservative to produce between-group effects Abstract Background and Aims : Previous studies have shown that antidepressants reduce inflammation in animal models of colitis . The present trial aim ed to examine whether fluoxetine added to st and ard therapy for Crohn ’s disease [ CD ] maintained remission , improved quality of life [ QoL ] and /or mental health in people with CD as compared to placebo . Methods : A parallel r and omized double-blind placebo controlled trial was conducted . Participants with clinical ly established CD , with quiescent or only mild disease , were r and omly assigned to receive either fluoxetine 20 mg daily or placebo , and followed for 12 months . Participants provided blood and stool sample s and completed mental health and QoL question naires . Immune functions were assessed by stimulated cytokine secretion [ CD3/CD28 stimulation ] and flow cytometry for cell type . Linear mixed-effects models were used to compare groups . Results : Of the 26 participants , 14 were r and omized to receive fluoxetine and 12 to placebo . Overall , 14 [ 54 % ] participants were male . The mean age was 37.4 [ SD=13.2 ] years . Fluoxetine had no effect on inflammatory bowel disease activity measured using either the Crohn ’s Disease Activity Index [ F(3 , 27.5)=0.064 , p=0.978 ] or faecal calprotectin [ F(3 , 32.5)=1.08 , p=0.371 ] , but did have modest effects on immune function . There was no effect of fluoxetine on physical , psychological , social or environmental QoL , anxiety or depressive symptoms as compared to placebo [ all p>0.05 ] . Conclusions : In this small pilot clinical trial , fluoxetine was not superior to placebo in maintaining remission or improving QoL. [ ID : ACTRN12612001067864 . BACKGROUND & AIMS Activated granulocytes and monocytes/macrophages are implicated in the pathogenesis of ulcerative colitis . Open-label studies and clinical experience in Japan and Europe have suggested that granulocyte/monocyte apheresis is safe and effective in treating ulcerative colitis . METHODS We evaluated the efficacy of granulocyte/monocyte apheresis in a r and omized , double-blind , sham-controlled trial in patients with active moderate-to-severe ulcerative colitis ( Mayo score 6 - 11 ) in community-based and tertiary care centers . As intervention , we used granulocyte/monocyte apheresis with the Adacolumn Apheresis System ( JIMRO , Ltd , Takasaki , Japan ) or sham apheresis in a 2:1 ratio for 9 weeks of treatment in a North American pivotal study ( N = 168 ) and in a smaller , companion study of identical design conducted in Europe and Japan ( N = 47 ) . RESULTS In the pivotal study , clinical remission rates ( Mayo score 0 - 2 , with scores of 0 on rectal bleeding and 0 or 1 on endoscopic examination ) were 17 % and 11 % for the granulocyte/monocyte apheresis ( n = 112)- and sham-treatment groups , respectively ( n = 56 ; P = .361 ) . Clinical response ( Mayo score reduction of > /=3 points from baseline ) was observed in 44 % and 39 % of patients , respectively ( P = .620 ) . Similar changes were observed for the apheresis- and sham-treatment groups for endoscopic remission and response , and changes in Mayo and quality -of-life scores . The companion study and pooled data from both studies also yielded similar results . CONCLUSIONS In this study , granulocyte/monocyte apheresis was well tolerated but did not demonstrate efficacy for induction of clinical remission or response in patients with moderate-to-severe ulcerative colitis BACKGROUND & AIMS This study evaluated the efficacy and safety of adalimumab , a fully human , anti-tumor necrosis factor monoclonal antibody administered subcutaneously , in the maintenance of response and remission in patients with moderate to severe Crohn 's disease ( CD ) . METHODS Patients received open-label induction therapy with adalimumab 80 mg ( week 0 ) followed by 40 mg ( week 2 ) . At week 4 , patients were stratified by response ( decrease in Crohn 's Disease Activity Index > or = 70 points from baseline ) and r and omized to double-blind treatment with placebo , adalimumab 40 mg every other week ( eow ) , or adalimumab 40 mg weekly through week 56 . Co- primary end points were the percentages of r and omized responders who achieved clinical remission ( Crohn 's Disease Activity Index score < 150 ) at weeks 26 and 56 . RESULTS The percentage of r and omized responders in remission was significantly greater in the adalimumab 40-mg eow and 40-mg weekly groups versus placebo at week 26 ( 40 % , 47 % , and 17 % , respectively ; P < .001 ) and week 56 ( 36 % , 41 % , and 12 % , respectively ; P < .001 ) . No significant differences in efficacy between adalimumab eow and weekly were observed . More patients receiving placebo discontinued treatment because of an adverse event ( 13.4 % ) than those receiving adalimumab ( 6.9 % and 4.7 % in the 40-mg eow and 40-mg weekly groups , respectively ) . CONCLUSIONS Among patients who responded to adalimumab  , both adalimumab eow and weekly were significantly more effective than placebo in maintaining remission in moderate to severe CD through 56 weeks . Adalimumab was well-tolerated , with a safety profile consistent with previous experience with the drug OBJECTIVE This study vali date d a brief measure of fatigue in rheumatoid arthritis ( RA ) , the Functional Assessment of Chronic Illness Therapy ( FACIT ) Fatigue Scale . METHODS The FACIT Fatigue was tested along with measures previously vali date d in RA : the Multidimensional Assessment of Fatigue ( MAF ) and Medical Outcomes Study Short-Form 36 ( SF-36 ) Vitality . The sample included 636 patients with RA enrolled in a 24 week double blind , r and omized clinical trial ( RCT ) of adalimumab versus placebo . RESULTS The FACIT Fatigue showed good internal consistency ( alpha = 0.86 to 0.87 ) , strong association with SF-36 Vitality ( r = 0.73 to 0.84 ) and MAF ( r = -0.84 to -0.88 ) , and the ability to differentiate patients according to clinical change using the American College of Rheumatology ( ACR ) response criteria ( ACR 20/50/70 ) . Psychometric performance of the FACIT Fatigue scale was comparable to that of the other 2 fatigue measures . A minimally important difference in FACIT Fatigue change score of 3 - 4 points was confirmed in a separate sample of 271 patients with RA enrolled in a second double blind RCT of adalimumab versus placebo . CONCLUSION The FACIT Fatigue is a brief , valid measure for monitoring this important symptom and its effects on patients with RA BACKGROUND & AIMS Immunomodulator therapy is effective for patients with Crohn 's disease ( CD ) but has not been shown to affect disease progression , presumably because it is given too late after diagnosis 
    Output:
    
agent
***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 Endogenous opioid peptides have been shown to play a role in the development and /or perpetuation of inflammation . We hypothesize that the endogenous opioid system is involved in inflammatory bowel disease , and antagonism of the opioid – opioid receptor will lead to reversal of inflammation . Aims A r and omized double-blind placebo-controlled study was design ed to test the efficacy and safety of an opioid antagonist for 12 weeks in adults with active Crohn ’s disease . Methods Forty subjects with active Crohn ’s disease were enrolled in the study . R and omized patients received daily oral administration of 4.5-mg naltrexone or placebo . Providers and patients were masked to treatment assignment . The primary outcome was the proportion of subjects in each arm with a 70-point decline in Crohn ’s Disease Activity Index score ( CDAI ) . The secondary outcome included mucosal healing based upon colonoscopy appearance and histology . Results Eighty-eight percent of those treated with naltrexone had at least a 70-point decline in CDAI scores compared to 40 % of placebo-treated patients ( p = 0.009 ) . After 12 weeks , 78 % of subjects treated with naltrexone exhibited an endoscopic response as indicated by a 5-point decline in the Crohn ’s disease endoscopy index severity score ( CDEIS ) from baseline compared to 28 % response in placebo-treated controls ( p = 0.008 ) , and 33 % achieved remission with a CDEIS score < 6 , whereas only 8 % of those on placebo showed the same change . Fatigue was the only side effect reported that was significantly greater in subjects receiving placebo . Conclusions Naltrexone improves clinical and inflammatory activity of subjects with moderate to severe Crohn ’s disease compared to placebo-treated controls . Strategies to alter the endogenous opioid system provide promise for the treatment of Crohn ’s disease AIM To study the effect of infliximab on fatigue in relation to cytokine levels in Crohn 's disease ( CD ) patients . METHODS Fourteen CD patients were blinded for treatment and received placebo at baseline , and infliximab 2 wk later , with a follow-up of 4 wk . Blood sample s were drawn on a regular basis , and question naires on fatigue , depression , quality of life , and clinical disease activity were completed at regular intervals . RESULTS After placebo infusion , fatigue scores decreased within 3 d ( 3.5 points + /- 1.1 , P < or= 0.01 ) , but returned to baseline values 14 d after this infusion . The drop of fatigue scores following infliximab infusion sustained until the end of the study ( 3.8 points + /- 1.4 , P < or= 0.05 ) . Quality of life was increased at the end of the study compared to baseline values ( 138.6 + /- 9.4 vs 179.4 + /- 6.7 ; P < or= 0.005 ) , whereas depression scores were decreased ( 20.4 + /- 9.4 vs 11.3 + /- 2.2 ; P < or= 0.01 ) . No correlation between the severity of fatigue and the level of cytokines was observed . CONCLUSION The reduction of fatigue after infliximab infusion is subjective to a placebo effect . The effect of infliximab on fatigue , however , persists while the placebo effect disappears after a short period of time . A clear role of cytokines could not be substantiated In this paper the psychometric properties of the multidimensional fatigue inventory ( MFI-20 ) are established further in cancer patients . The MFI is a 20-item self-report instrument design ed to measure fatigue . It covers the following dimensions : general fatigue , physical fatigue , reduced activity , reduced motivation and mental fatigue . The instrument was used in a Dutch and Scottish sample of cancer patients receiving radiotherapy .  The dimensional structure was assessed using confirmatory factor analyses ( Lisrel 's unweighted least-squares method ) . The hypothesised five-factor model appeared to fit the data in both sample s ( adjusted goodness of fit ; AGFI : 0.97 and 0.98 ) . Internal consistency of the separate scales was good in both the Dutch and Scottish sample s with Cronbach 's alpha coefficients ranging from 0.79 to 0.93 . Construct validity was assessed by correlating the MFI-20 to activities of daily living , anxiety and depression . Significant relations were assumed . Convergent validity was investigated by correlating the MFI scales with a visual analogue scale measuring fatigue and with a fatigue-scale derived from the Rotterdam Symptom Checklist . Results support the validity of the MFI-20 . The highly similar results in the Dutch and Scottish sample suggest that the portrayal of fatigue using the MFI-20 is quite robust Although inflammatory bowel disease ( IBD ) affects patients ' psychological well-being , previous educational programs have failed to demonstrate effects on psychosocial outcomes and quality of life . Therefore , we developed a group-based psychoeducational program that combined provision of both medical information and psychological self-management skills , delivered in an interactive manner , and evaluated it in a large , cluster-r and omized trial . We assigned 540 rehabilitation in patients suffering from IBD ( mean age 43 years , 66 % female ) to either the new intervention or a control group comprising the same overall intensity and the same medical information , but only general psychosocial information . The primary outcome was patient-reported IBD-related concerns . Secondary outcomes included disease knowledge , coping , self-management skills , fear of progression , anxiety , depression and quality of life . Assessment s took place at baseline , end of rehabilitation and after 3 and 12 months . The psychoeducational self-management program did not prove superior to the control group regarding primary and secondary outcomes . However , positive changes over time occurred in both groups regarding most outcomes . The superior effectiveness of the newly developed psychoeducational program could not be demonstrated . Since the intervention and control groups may have been too similar , this trial may have been too conservative to produce between-group effects Abstract Background and Aims : Previous studies have shown that antidepressants reduce inflammation in animal models of colitis . The present trial aim ed to examine whether fluoxetine added to st and ard therapy for Crohn ’s disease [ CD ] maintained remission , improved quality of life [ QoL ] and /or mental health in people with CD as compared to placebo . Methods : A parallel r and omized double-blind placebo controlled trial was conducted . Participants with clinical ly established CD , with quiescent or only mild disease , were r and omly assigned to receive either fluoxetine 20 mg daily or placebo , and followed for 12 months . Participants provided blood and stool sample s and completed mental health and QoL question naires . Immune functions were assessed by stimulated cytokine secretion [ CD3/CD28 stimulation ] and flow cytometry for cell type . Linear mixed-effects models were used to compare groups . Results : Of the 26 participants , 14 were r and omized to receive fluoxetine and 12 to placebo . Overall , 14 [ 54 % ] participants were male . The mean age was 37.4 [ SD=13.2 ] years . Fluoxetine had no effect on inflammatory bowel disease activity measured using either the Crohn ’s Disease Activity Index [ F(3 , 27.5)=0.064 , p=0.978 ] or faecal calprotectin [ F(3 , 32.5)=1.08 , p=0.371 ] , but did have modest effects on immune function . There was no effect of fluoxetine on physical , psychological , social or environmental QoL , anxiety or depressive symptoms as compared to placebo [ all p>0.05 ] . Conclusions : In this small pilot clinical trial , fluoxetine was not superior to placebo in maintaining remission or improving QoL. [ ID : ACTRN12612001067864 . BACKGROUND & AIMS Activated granulocytes and monocytes/macrophages are implicated in the pathogenesis of ulcerative colitis . Open-label studies and clinical experience in Japan and Europe have suggested that granulocyte/monocyte apheresis is safe and effective in treating ulcerative colitis . METHODS We evaluated the efficacy of granulocyte/monocyte apheresis in a r and omized , double-blind , sham-controlled trial in patients with active moderate-to-severe ulcerative colitis ( Mayo score 6 - 11 ) in community-based and tertiary care centers . As intervention , we used granulocyte/monocyte apheresis with the Adacolumn Apheresis System ( JIMRO , Ltd , Takasaki , Japan ) or sham apheresis in a 2:1 ratio for 9 weeks of treatment in a North American pivotal study ( N = 168 ) and in a smaller , companion study of identical design conducted in Europe and Japan ( N = 47 ) . RESULTS In the pivotal study , clinical remission rates ( Mayo score 0 - 2 , with scores of 0 on rectal bleeding and 0 or 1 on endoscopic examination ) were 17 % and 11 % for the granulocyte/monocyte apheresis ( n = 112)- and sham-treatment groups , respectively ( n = 56 ; P = .361 ) . Clinical response ( Mayo score reduction of > /=3 points from baseline ) was observed in 44 % and 39 % of patients , respectively ( P = .620 ) . Similar changes were observed for the apheresis- and sham-treatment groups for endoscopic remission and response , and changes in Mayo and quality -of-life scores . The companion study and pooled data from both studies also yielded similar results . CONCLUSIONS In this study , granulocyte/monocyte apheresis was well tolerated but did not demonstrate efficacy for induction of clinical remission or response in patients with moderate-to-severe ulcerative colitis BACKGROUND & AIMS This study evaluated the efficacy and safety of adalimumab , a fully human , anti-tumor necrosis factor monoclonal antibody administered subcutaneously , in the maintenance of response and remission in patients with moderate to severe Crohn 's disease ( CD ) . METHODS Patients received open-label induction therapy with adalimumab 80 mg ( week 0 ) followed by 40 mg ( week 2 ) . At week 4 , patients were stratified by response ( decrease in Crohn 's Disease Activity Index > or = 70 points from baseline ) and r and omized to double-blind treatment with placebo , adalimumab 40 mg every other week ( eow ) , or adalimumab 40 mg weekly through week 56 . Co- primary end points were the percentages of r and omized responders who achieved clinical remission ( Crohn 's Disease Activity Index score < 150 ) at weeks 26 and 56 . RESULTS The percentage of r and omized responders in remission was significantly greater in the adalimumab 40-mg eow and 40-mg weekly groups versus placebo at week 26 ( 40 % , 47 % , and 17 % , respectively ; P < .001 ) and week 56 ( 36 % , 41 % , and 12 % , respectively ; P < .001 ) . No significant differences in efficacy between adalimumab eow and weekly were observed . More patients receiving placebo discontinued treatment because of an adverse event ( 13.4 % ) than those receiving adalimumab ( 6.9 % and 4.7 % in the 40-mg eow and 40-mg weekly groups , respectively ) . CONCLUSIONS Among patients who responded to adalimumab  , both adalimumab eow and weekly were significantly more effective than placebo in maintaining remission in moderate to severe CD through 56 weeks . Adalimumab was well-tolerated , with a safety profile consistent with previous experience with the drug OBJECTIVE This study vali date d a brief measure of fatigue in rheumatoid arthritis ( RA ) , the Functional Assessment of Chronic Illness Therapy ( FACIT ) Fatigue Scale . METHODS The FACIT Fatigue was tested along with measures previously vali date d in RA : the Multidimensional Assessment of Fatigue ( MAF ) and Medical Outcomes Study Short-Form 36 ( SF-36 ) Vitality . The sample included 636 patients with RA enrolled in a 24 week double blind , r and omized clinical trial ( RCT ) of adalimumab versus placebo . RESULTS The FACIT Fatigue showed good internal consistency ( alpha = 0.86 to 0.87 ) , strong association with SF-36 Vitality ( r = 0.73 to 0.84 ) and MAF ( r = -0.84 to -0.88 ) , and the ability to differentiate patients according to clinical change using the American College of Rheumatology ( ACR ) response criteria ( ACR 20/50/70 ) . Psychometric performance of the FACIT Fatigue scale was comparable to that of the other 2 fatigue measures . A minimally important difference in FACIT Fatigue change score of 3 - 4 points was confirmed in a separate sample of 271 patients with RA enrolled in a second double blind RCT of adalimumab versus placebo . CONCLUSION The FACIT Fatigue is a brief , valid measure for monitoring this important symptom and its effects on patients with RA BACKGROUND & AIMS Immunomodulator therapy is effective for patients with Crohn 's disease ( CD ) but has not been shown to affect disease progression , presumably because it is given too late after diagnosis 
    Output:
    