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: Forty patients with rheumatoid arthritis and upper gastrointestinal lesions due to non-steroidal anti-inflammatory drugs entered a prospect i ve 6-month double-blind placebo controlled study of dietary supplementation with gamma-linolenic acid 540 mg/day . Nineteen patients received active therapy ( as evening primrose oil 6 g/day ) and 21 received placebo ( olive oil 6 g/day ) . No patient stopped non-steroidal anti-inflammatory therapy but three patients in each group reduced their dose . Other results showed a significant reduction in morning stiffness with gamma-linolenic acid at 3 months and reduction in pain and articular index at 6 months with olive oil . Whilst gamma-linolenic acid may produce mild improvement in rheumatoid arthritis , olive oil may itself have hitherto unrecognized benefits Sixteen patients with rheumatoid arthritis entered a trial to determine the clinical and biochemical effects of dietary supplementation with fractionated fish oil fatty acids . A r and omised , double blind , placebo controlled crossover design with 12 week treatment periods was used . Treatment with non-steroidal anti-inflammatory drugs and with disease modifying drugs was continued throughout the study . Placebo consisted of fractionated coconut oil . The following results favoured fish oil rather than placebo :  joint swelling index and duration of early morning stiffness . Other clinical indices improved but did not reach statistical significance . During fish oil supplementation relative amounts of eicosapentaenoic acid and docosahexaenoic acid in the plasma cholesterol ester and neutrophil membrane phospholipid fractions increased , mainly at the expense of the omega-6 fatty acids . The mean neutrophil leucotriene B4 production in vitro showed a reduction after 12 weeks of fish oil supplementation . Leucotriene B5 production , which could not be detected either in the control or in the placebo period , rose to substantial quantities during fish oil treatment . This study shows that dietary fish oil supplementation is effective in suppressing clinical symptoms of rheumatoid arthritis OBJECTIVES Dose-dependant gastrointestinal and cardiovascular side-effects limit the use of NSAIDs in the management of RA . The n-3 essential fatty acids ( EFAs ) have previously demonstrated some anti-inflammatory and NSAID-sparing properties . The objective of this study was to determine whether cod liver oil supplementation helps reduce daily NSAID requirement of patients with RA . METHODS Dual-centre , double-blind placebo-controlled r and omized study of 9 months ' duration . Ninety-seven patients with RA were r and omized to take either 10 g of cod liver oil containing 2.2 g of n-3 EFAs or air-filled identical placebo capsules . Documentation of NSAID daily requirement , clinical and laboratory parameters of RA disease activity and safety checks were done at 0 , 4 , 12 , 24 and 36 weeks . At 12 weeks , patients were instructed to gradually reduce , and if possible , stop their NSAID intake . Relative reduction of daily NSAID requirement by > 30 % after 9 months was the primary outcome measure . RESULTS Fifty-eight patients ( 60 % ) completed the study . Out of 49 patients 19 ( 39 % ) in the cod liver oil group and out of 48 patients 5 ( 10 % ) in the placebo group were able to reduce their daily NSAID requirement by > 30 % ( P = 0.002 , chi-squared test ) . No differences between the groups were observed in the clinical parameters of RA disease activity or in the side-effects observed . CONCLUSIONS This study suggests that cod liver oil supplements containing n-3 fatty acids can be used as NSAID-sparing agents in RA patients How should health care professionals choose among the many therapies cl aim ed to be efficacious for treating specific disorders ? The practice of evidence -based medicine provides an answer . Advocates of this approach urge health care professionals to base treatment choices on the best evidence from systematic research on both the efficacy and adverse effects of various therapeutic alternatives . Ideally , health care professionals would compare different treatments by referring to r and omized , double-blind , head-to-head trials that compared the treatment options . Although individual medications are typically well research ed when these placebo-controlled studies are performed , studies that directly compare treatments are rare . In the absence of direct head-to-head trials , other evidence comes from indirect comparisons of two or more therapies by examining individual studies involving each treatment . This article provides an introductory review of methods of such indirect comparisons of therapies across studies , provides examples of how these methods can be used to make treatment decisions , and presents a general overview of relevant issues and statistics for readers interested in underst and ing these methods more thoroughly Forty-nine patients with active rheumatoid arthritis completed a 24-week , prospect i ve , double-blind , r and omized study of dietary supplementation with 2 different dosages of fish oil and 1 dosage of olive oil . Clinical evaluations were performed at baseline and every 6 weeks thereafter , and immunologic variables were measured at baseline and after 24 weeks of study . The 3 groups of patients were matched for age , sex , disease severity , and use of disease-modifying antirheumatic drugs ( DMARDs ) . Subjects continued receiving DMARDs and other background medications without change during the study . Twenty patients consumed daily dietary supplements of n3 fatty acids containing 27 mg/kg eicosapentaenoic acid ( EPA ) and 18 mg/kg docosahexaenoic acid ( DHA ) ( low dose ) , 17 patients ingested 54 mg/kg EPA and 36 mg/kg DHA ( high dose ) , and 12 patients ingested olive oil capsules containing 6.8 gm of oleic acid . Significant improvements from baseline in the number of tender joints were noted in the low-dose group at week 24 ( P = 0.05 ) and in the high-dose group at week 18 ( P = 0.04 ) and 24 ( P = 0.02 ) . Significant decreases from baseline in the number of swollen joints were noted in the low-dose group at weeks 12 ( P = 0.003 ) , 18 ( P = 0.002 ) , and 24 ( P = 0.001 ) and in the high-dose group at weeks 12 ( P = 0.0001 ) , 18 ( P = 0.008 ) , and 24 ( P = 0.02 ) . A total of 5 of 45 clinical measures were significantly changed from baseline in the olive oil group , 8 of 45 in the low-dose fish oil group , and 21 of 45 in the high-dose fish oil group during the study ( P = 0.0002 ) . Neutrophil leukotriene B4 production decreased by 19 % from baseline in the low-dose fish oil group ( P = 0.0003 ) and 20 % in the high-dose group ( P = 0.03 ) , while macrophage interleukin-1 production decreased by 38.5 % in the olive oil group ( P not significant ) , 40.6 % in the low-dose group ( P = 0.06 ) , and 54.7 % in the high-dose group ( P = 0.0005 ) . Tritiated thymidine incorporation in peripheral blood mononuclear cells after stimulation with concanavalin A increased significantly in all 3 groups after 24 weeks , compared with baseline values . We conclude that the clinical benefits of dietary supplementation with omega-3 fatty acids are more commonly observed in patients consuming higher dosages of fish oil  for time intervals that are longer than those previously studied . Dietary supplementation with olive oil is also associated with certain changes in immune function , which require further investigation In a controlled , double blind , clinical trial we tested the effect of dietary omega-3 fatty acid supplementation with and without naproxen and placebo , respectively , in 67 patients with active rheumatoid arthritis . The patients were r and omized into 3 groups that received the following treatment : Group 1 , corn oil ( " placebo omega-3 fatty acids " ) , 7 g/day for 16 weeks , and naproxen , 750 mg/day for 10 weeks followed by a stepwise reduction to 0 mg/day during the following 3 weeks ; Group 2 , omega-3 fatty acids , 3.8 g of eicosapentaenoic acid plus 2.0 g of docosahexaenoic acid , and naproxen , 750 mg/day for 16 weeks ; and Group 3 , omega-3 fatty acids as Group 2 and naproxen as Group 1 . At the end of the trial , patients in Group 2 had improved with respect to duration of morning stiffness and global assessment by physician and patient . In Groups 1 and 3 there was a significant deterioration for most of the variables measured . However , for duration of morning stiffness the deterioration was significantly less pronounced in Group 3 compared with Group 1 . These effects might be ascribed to the dietary omega-3 fatty acid supplementation In rheumatoid arthris s various pro-inflammatory metabolites of arachidonic acid ( AA ) , such as leukotriene B4 ( LTB4 ) and prostagl and in E2 ( PGE2 ) , contribute to tissue destruction and pain . In contrast to AA , which is an omega-6 fatty acid , the omega-3 fatty acids , after having been liberated from the cell membrane phospholipids , are further converted into the non-or anti-inflammatory eicosanoids LTB5 and PGI3 . AA concentration is an important regulatory step in the synthesis of both prostanoids and leukotriens . Dietary supplementation with eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) has therefore been used to decrease the ratio of AA to EPA or DHA to obtain beneficial clinical effects . EPA and DHA are found in animal fat and are quite expensive compared to their precursor alpha-linolenic acid ( alpha-LNA ) found in flaxseed oil . We , therefore , performed a placebocontrolled trial with alpha-LNA in 22 patients with rheumatoid arthritis , using a linoleic acid preparation as a placebo . After a 3-month follow-up , the treatment group showed an increased bleeding time , but the clinical , subjective ( global assessment , classification of functional status , joint score index , visual analogue scale , pain tendereness score ) and laboratory parameters ( haemoglobin , erythrocyte sedimentation rate , C-reactive protein ) did not show any statistical alterations . AA , EPA and DHA did not change either in spite of a significant increase in alpha-LNA in the treatment group . Thus , 3-month 's supplementation with alpha-LNA did not prove to be beneficial in rheumatoid arthritis Therapeutic effects of fish oil ( 10 g/day ) in rheumatoid arthritis were investigated in a r and omized , controlled , double-blind study . Forty-three patients completing the study were evaluated at 0 , 3 and 6 months . The nutrient intake in the fish oil group and in the control group was essentially similar . In the fish oil group , the percentage of n-3 fatty acids in serum phosphatidylcholine increased by 9.6 ( range 2.6 - 16.1 ) . Patients in the fish oil group reported a significantly decreased consumption of NSAID at 3 and 6 months , and the status of global arthritic activity improved at 3 months in physician 's assessment . Control patients reported an increased global arthritic activity at 6 months . No change was found in patient assessment of pain , duration of morning stiffness or functional capacity . Essentially no change occurred in biochemical markers of inflammation . We conclude that fish oil has small anti-inflammatory effects with at most a NSAID-saving potential . The value of prolonged supplementation remains to be evaluated OBJECTIVE This study evaluated whether supplementation with olive oil could improve clinical and laboratory parameters of disease activity in patients who had rheumatoid arthritis and were using fish oil supplements .  METHODS Forty-three patients ( 34 female , 9 male ; mean age = 49 + /- 19y ) were investigated in a parallel r and omized design . Patients were assigned to one of three groups . In addition to their usual medication , the first group ( G1 ) received placebo ( soy oil ) , the second group ( G2 ) received fish oil omega-3 fatty acids ( 3 g/d ) , and the third group ( G3 ) received fish oil omega-3 fatty acids ( 3 g/d ) and 9.6 mL of olive oil .  Disease activity was measured by clinical and laboratory indicators at the beginning of the study and after 12 and 24 wk . Patients ' satisfaction in activities of daily living was also measured . RESULTS There was a statistically significant improvement ( P < 0.05 ) in G2 and G3 in relation to G1 with respect to joint pain intensity , right and left h and grip strength after 12 and 24 wk , duration of morning stiffness , onset of fatigue , Ritchie 's articular index for pain joints after 24 wk , ability to bend down to pick up clothing from the floor , and getting in and out of a car after 24 wk . G3 , but not G2 , in relation to G1 showed additional improvements with respect to duration of morning stiffness after 12 wk , patient global assessment after 12 and 24 wk , ability to turn faucets on and off after 24 wk , and rheumatoid 
    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: Forty patients with rheumatoid arthritis and upper gastrointestinal lesions due to non-steroidal anti-inflammatory drugs entered a prospect i ve 6-month double-blind placebo controlled study of dietary supplementation with gamma-linolenic acid 540 mg/day . Nineteen patients received active therapy ( as evening primrose oil 6 g/day ) and 21 received placebo ( olive oil 6 g/day ) . No patient stopped non-steroidal anti-inflammatory therapy but three patients in each group reduced their dose . Other results showed a significant reduction in morning stiffness with gamma-linolenic acid at 3 months and reduction in pain and articular index at 6 months with olive oil . Whilst gamma-linolenic acid may produce mild improvement in rheumatoid arthritis , olive oil may itself have hitherto unrecognized benefits Sixteen patients with rheumatoid arthritis entered a trial to determine the clinical and biochemical effects of dietary supplementation with fractionated fish oil fatty acids . A r and omised , double blind , placebo controlled crossover design with 12 week treatment periods was used . Treatment with non-steroidal anti-inflammatory drugs and with disease modifying drugs was continued throughout the study . Placebo consisted of fractionated coconut oil . The following results favoured fish oil rather than placebo :  joint swelling index and duration of early morning stiffness . Other clinical indices improved but did not reach statistical significance . During fish oil supplementation relative amounts of eicosapentaenoic acid and docosahexaenoic acid in the plasma cholesterol ester and neutrophil membrane phospholipid fractions increased , mainly at the expense of the omega-6 fatty acids . The mean neutrophil leucotriene B4 production in vitro showed a reduction after 12 weeks of fish oil supplementation . Leucotriene B5 production , which could not be detected either in the control or in the placebo period , rose to substantial quantities during fish oil treatment . This study shows that dietary fish oil supplementation is effective in suppressing clinical symptoms of rheumatoid arthritis OBJECTIVES Dose-dependant gastrointestinal and cardiovascular side-effects limit the use of NSAIDs in the management of RA . The n-3 essential fatty acids ( EFAs ) have previously demonstrated some anti-inflammatory and NSAID-sparing properties . The objective of this study was to determine whether cod liver oil supplementation helps reduce daily NSAID requirement of patients with RA . METHODS Dual-centre , double-blind placebo-controlled r and omized study of 9 months ' duration . Ninety-seven patients with RA were r and omized to take either 10 g of cod liver oil containing 2.2 g of n-3 EFAs or air-filled identical placebo capsules . Documentation of NSAID daily requirement , clinical and laboratory parameters of RA disease activity and safety checks were done at 0 , 4 , 12 , 24 and 36 weeks . At 12 weeks , patients were instructed to gradually reduce , and if possible , stop their NSAID intake . Relative reduction of daily NSAID requirement by > 30 % after 9 months was the primary outcome measure . RESULTS Fifty-eight patients ( 60 % ) completed the study . Out of 49 patients 19 ( 39 % ) in the cod liver oil group and out of 48 patients 5 ( 10 % ) in the placebo group were able to reduce their daily NSAID requirement by > 30 % ( P = 0.002 , chi-squared test ) . No differences between the groups were observed in the clinical parameters of RA disease activity or in the side-effects observed . CONCLUSIONS This study suggests that cod liver oil supplements containing n-3 fatty acids can be used as NSAID-sparing agents in RA patients How should health care professionals choose among the many therapies cl aim ed to be efficacious for treating specific disorders ? The practice of evidence -based medicine provides an answer . Advocates of this approach urge health care professionals to base treatment choices on the best evidence from systematic research on both the efficacy and adverse effects of various therapeutic alternatives . Ideally , health care professionals would compare different treatments by referring to r and omized , double-blind , head-to-head trials that compared the treatment options . Although individual medications are typically well research ed when these placebo-controlled studies are performed , studies that directly compare treatments are rare . In the absence of direct head-to-head trials , other evidence comes from indirect comparisons of two or more therapies by examining individual studies involving each treatment . This article provides an introductory review of methods of such indirect comparisons of therapies across studies , provides examples of how these methods can be used to make treatment decisions , and presents a general overview of relevant issues and statistics for readers interested in underst and ing these methods more thoroughly Forty-nine patients with active rheumatoid arthritis completed a 24-week , prospect i ve , double-blind , r and omized study of dietary supplementation with 2 different dosages of fish oil and 1 dosage of olive oil . Clinical evaluations were performed at baseline and every 6 weeks thereafter , and immunologic variables were measured at baseline and after 24 weeks of study . The 3 groups of patients were matched for age , sex , disease severity , and use of disease-modifying antirheumatic drugs ( DMARDs ) . Subjects continued receiving DMARDs and other background medications without change during the study . Twenty patients consumed daily dietary supplements of n3 fatty acids containing 27 mg/kg eicosapentaenoic acid ( EPA ) and 18 mg/kg docosahexaenoic acid ( DHA ) ( low dose ) , 17 patients ingested 54 mg/kg EPA and 36 mg/kg DHA ( high dose ) , and 12 patients ingested olive oil capsules containing 6.8 gm of oleic acid . Significant improvements from baseline in the number of tender joints were noted in the low-dose group at week 24 ( P = 0.05 ) and in the high-dose group at week 18 ( P = 0.04 ) and 24 ( P = 0.02 ) . Significant decreases from baseline in the number of swollen joints were noted in the low-dose group at weeks 12 ( P = 0.003 ) , 18 ( P = 0.002 ) , and 24 ( P = 0.001 ) and in the high-dose group at weeks 12 ( P = 0.0001 ) , 18 ( P = 0.008 ) , and 24 ( P = 0.02 ) . A total of 5 of 45 clinical measures were significantly changed from baseline in the olive oil group , 8 of 45 in the low-dose fish oil group , and 21 of 45 in the high-dose fish oil group during the study ( P = 0.0002 ) . Neutrophil leukotriene B4 production decreased by 19 % from baseline in the low-dose fish oil group ( P = 0.0003 ) and 20 % in the high-dose group ( P = 0.03 ) , while macrophage interleukin-1 production decreased by 38.5 % in the olive oil group ( P not significant ) , 40.6 % in the low-dose group ( P = 0.06 ) , and 54.7 % in the high-dose group ( P = 0.0005 ) . Tritiated thymidine incorporation in peripheral blood mononuclear cells after stimulation with concanavalin A increased significantly in all 3 groups after 24 weeks , compared with baseline values . We conclude that the clinical benefits of dietary supplementation with omega-3 fatty acids are more commonly observed in patients consuming higher dosages of fish oil  for time intervals that are longer than those previously studied . Dietary supplementation with olive oil is also associated with certain changes in immune function , which require further investigation In a controlled , double blind , clinical trial we tested the effect of dietary omega-3 fatty acid supplementation with and without naproxen and placebo , respectively , in 67 patients with active rheumatoid arthritis . The patients were r and omized into 3 groups that received the following treatment : Group 1 , corn oil ( " placebo omega-3 fatty acids " ) , 7 g/day for 16 weeks , and naproxen , 750 mg/day for 10 weeks followed by a stepwise reduction to 0 mg/day during the following 3 weeks ; Group 2 , omega-3 fatty acids , 3.8 g of eicosapentaenoic acid plus 2.0 g of docosahexaenoic acid , and naproxen , 750 mg/day for 16 weeks ; and Group 3 , omega-3 fatty acids as Group 2 and naproxen as Group 1 . At the end of the trial , patients in Group 2 had improved with respect to duration of morning stiffness and global assessment by physician and patient . In Groups 1 and 3 there was a significant deterioration for most of the variables measured . However , for duration of morning stiffness the deterioration was significantly less pronounced in Group 3 compared with Group 1 . These effects might be ascribed to the dietary omega-3 fatty acid supplementation In rheumatoid arthris s various pro-inflammatory metabolites of arachidonic acid ( AA ) , such as leukotriene B4 ( LTB4 ) and prostagl and in E2 ( PGE2 ) , contribute to tissue destruction and pain . In contrast to AA , which is an omega-6 fatty acid , the omega-3 fatty acids , after having been liberated from the cell membrane phospholipids , are further converted into the non-or anti-inflammatory eicosanoids LTB5 and PGI3 . AA concentration is an important regulatory step in the synthesis of both prostanoids and leukotriens . Dietary supplementation with eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) has therefore been used to decrease the ratio of AA to EPA or DHA to obtain beneficial clinical effects . EPA and DHA are found in animal fat and are quite expensive compared to their precursor alpha-linolenic acid ( alpha-LNA ) found in flaxseed oil . We , therefore , performed a placebocontrolled trial with alpha-LNA in 22 patients with rheumatoid arthritis , using a linoleic acid preparation as a placebo . After a 3-month follow-up , the treatment group showed an increased bleeding time , but the clinical , subjective ( global assessment , classification of functional status , joint score index , visual analogue scale , pain tendereness score ) and laboratory parameters ( haemoglobin , erythrocyte sedimentation rate , C-reactive protein ) did not show any statistical alterations . AA , EPA and DHA did not change either in spite of a significant increase in alpha-LNA in the treatment group . Thus , 3-month 's supplementation with alpha-LNA did not prove to be beneficial in rheumatoid arthritis Therapeutic effects of fish oil ( 10 g/day ) in rheumatoid arthritis were investigated in a r and omized , controlled , double-blind study . Forty-three patients completing the study were evaluated at 0 , 3 and 6 months . The nutrient intake in the fish oil group and in the control group was essentially similar . In the fish oil group , the percentage of n-3 fatty acids in serum phosphatidylcholine increased by 9.6 ( range 2.6 - 16.1 ) . Patients in the fish oil group reported a significantly decreased consumption of NSAID at 3 and 6 months , and the status of global arthritic activity improved at 3 months in physician 's assessment . Control patients reported an increased global arthritic activity at 6 months . No change was found in patient assessment of pain , duration of morning stiffness or functional capacity . Essentially no change occurred in biochemical markers of inflammation . We conclude that fish oil has small anti-inflammatory effects with at most a NSAID-saving potential . The value of prolonged supplementation remains to be evaluated OBJECTIVE This study evaluated whether supplementation with olive oil could improve clinical and laboratory parameters of disease activity in patients who had rheumatoid arthritis and were using fish oil supplements .  METHODS Forty-three patients ( 34 female , 9 male ; mean age = 49 + /- 19y ) were investigated in a parallel r and omized design . Patients were assigned to one of three groups . In addition to their usual medication , the first group ( G1 ) received placebo ( soy oil ) , the second group ( G2 ) received fish oil omega-3 fatty acids ( 3 g/d ) , and the third group ( G3 ) received fish oil omega-3 fatty acids ( 3 g/d ) and 9.6 mL of olive oil .  Disease activity was measured by clinical and laboratory indicators at the beginning of the study and after 12 and 24 wk . Patients ' satisfaction in activities of daily living was also measured . RESULTS There was a statistically significant improvement ( P < 0.05 ) in G2 and G3 in relation to G1 with respect to joint pain intensity , right and left h and grip strength after 12 and 24 wk , duration of morning stiffness , onset of fatigue , Ritchie 's articular index for pain joints after 24 wk , ability to bend down to pick up clothing from the floor , and getting in and out of a car after 24 wk . G3 , but not G2 , in relation to G1 showed additional improvements with respect to duration of morning stiffness after 12 wk , patient global assessment after 12 and 24 wk , ability to turn faucets on and off after 24 wk , and rheumatoid 
    Output:
    