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: Rheumatoid arthritis ( RA ) is an autoimmune disease that is characterized by chronic inflammation affecting target tissues including the joints , bones , and synovial membrane . However , the etiology and pathogenesis of RA remains to be determined , and investigations into the treatment of RA are imperative . Vitamin D ( Vit D ) was previously found to be associated with the activity of RA and exerts therapeutic benefits . The aim of the present study was to investigate the effect of Vit D on the recurrence rate of RA .  A total of 377 patients with RA at remission stage were divided into the normal Vit D group and the Vit D-deficient group according to their Vit D levels at baseline . The patients in the Vit D-deficient group were further r and omly allocated to receive treatment with or without Vit D. The patients were followed up for 24 months , and the visual analogue scale , as well as the number of pain and swelling joints were recorded every 2–3 months . In addition , C-reactive protein and the blood sedimentation rate were measured every 2–3 months to assess the recurrence of RA based on disease activity score 28 ( DAS28 ) . The recurrence rate of RA was 16.7 , 19.0 and 29.5 % for the normal Vit D group ( n=168 ) , Vit D treatment subgroup ( n=84 ) , and non-Vit D treatment subgroup ( n=88 ) , respectively . The recurrence rate of the normal Vit D group was lower , compared to the non-Vit D treatment subgroup , and the difference was statistically significant . However , the difference was not statistically significant between the Vit D treatment subgroup and non-Vit D treatment subgroup . In conclusion , a decreased level of  Vit D  is a risk factor for the recurrence of RA OBJECTIVE To identify predictors of moderate-to-severe systemic lupus erythematosus ( SLE ) flare in 562 patients treated with st and ard therapy alone in phase III belimumab trials , and to evaluate the impact of st and ard therapies on preventing flares . METHODS Post hoc analysis assessed baseline demographics , disease activity , and biomarkers in patients with and those without flare at treatment weeks 24 and 52 . Severe flare was defined by the modified SLE Flare Index ( SFI ) and the development of any new British Isles Lupus Assessment Group ( BILAG ) A domain score . Severe and moderate flare was defined by development of 1 new BILAG A domain score or 2 new BILAG B domain scores . Baseline characteristics associated with a ≥10 % absolute difference or a ≥50 % increase in flare rates were considered predictive . RESULTS Frequencies of flares over 52 weeks according to the SFI , any new BILAG A domain score , and 1 new BILAG A domain score or 2 new BILAG B domain scores were 23.7 % , 23.1 % , and 32.0 % , respectively . Flare predictors by univariate analysis on all 3 indices at weeks 24 and 52 were a score ≥12 on the Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index ( SELENA-SLEDAI ) ; anti-double-str and ed DNA ( anti-dsDNA ) positivity ; proteinuria ( ≥0.5 gm/24 hours ) ; BILAG renal , vasculitic , and hematologic scores ; elevated C-reactive protein levels ; and B lymphocyte stimulator ( BLyS ) levels ≥2 ng/ml . Independent predictors by multivariate analysis at week 52 were SELENA-SLEDAI and /or BILAG renal involvement and anti-dsDNA ≥200 IU/ml ( on all 3 indices ) ; SELENA-SLEDAI and /or BILAG neurologic and vasculitic involvement ( on 2 indices : any new BILAG A domain score and 1 new BILAG A domain score or 2 new BILAG B domain scores ) ; BLyS levels ≥2 ng/ml ( on 2 indices : the SFI and 1 new BILAG A domain score or 2 new BILAG B domain scores ) ; and low C3 level ( on the SFI ) . Baseline medications did not significantly decrease or increase moderate-to-severe SLE flare risk . CONCLUSION Patients who were receiving st and ard SLE therapy and had renal , neurologic , or vasculitic involvement , elevated anti-dsDNA or BLyS levels , or low C3 had increased risk of clinical ly meaningful flare over 1 year . Hydroxychloroquine use was not predictive To determine the efficacy of oral vitamin D [ 25(OH)D ] in patients with active rheumatoid arthritis ( RA ) who are in methotrexate ( MTX ) therapy , patients receiving stable doses of MTX  were r and omized to one of two dose groups and received 12 weeks of double-blind vitamin D[25(OH)D ] ( 50,000 IU per week ) or matching placebo . The moderate and major efficacy measure was the proportion of patients with > 0.6 and > 1.2 improvement in RA based on the Disease Activity Score 28(DAS 28 ) at 12 weeks . Safety measures included adverse events and laboratory assessment s. On a background of MTX , the percentage of patients with a moderate/major DAS 28 response at week 12 in the vitamin D groups ( 76/44 % ) was not significantly different from placebo ( 64.6/33.4 % ) . Adverse events were typically mild and included small hepatic enzyme elevation ; we did not have any undesirable events result ing in discontinuation of study drug . In patients with active RA receiving stable doses of MTX , vitamin D showed non-significant improvement in efficacy outcomes compared to placebo Objective . We determined the prevalence of and risk factors for British Isles Lupus Activity Group ( BILAG ) flare in patients with systemic lupus erythematosus ( SLE ) . Methods . We followed 299 patients for 1 year with the  BILAG scores  calculated using British Lupus Integrated Prospect i ve System software and confirmed with manual calculation . Results . “ A ” flares occurred at a rate of 0.254/year , “ B ” flares 1.637/year , and A or B flares 1.765/year . The most common A flares were renal and mucocutaneous . The most common B flares were hematologic , renal , mucocutaneous , and musculoskeletal . Risk factors for a later A or B flare in the hematological system included : low C3 ( p < 0.0001 ) , low C4 ( p = 0.0004 ) , and positive anti-double-str and ed (ds)DNA ( p = 0.003 ) ; in the mucocutaneous system : low C3 ( p = 0.02 ) and low C4 ( p = 0.0004 ) ; and in the renal system : low C3 ( p = 0.02 ) and low C4 ( p = 0.02 ) . In a stepwise regression model , only ethnicity ( p = 0.02 ) and low C4 ( p = 0.0002 ) remained as independent predictors of later A or 2B flares . Conclusion . The organ system distribution of A and B flares is very different , with A flares more common in renal and mucocutaneous , and B flares more common in hematologic and renal systems . A or 2B flares are significantly more common in African Americans and in patients with abnormal serologies ( low C3 , low C4 , or high anti-dsDNA ) . If flare is an outcome in an SLE clinical trial , these factors must be balanced by taking them into account at baseline in terms of r and omization , or by statistical adjustment in final analyses BACKGROUND The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal . METHODS We recruited 36,282 postmenopausal women , 50 to 79 years of age , who were already enrolled in a Women 's Health Initiative ( WHI ) clinical trial . We r and omly assigned participants to receive 1000 mg of elemental [ corrected ] calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo .  Fractures were ascertained for an average follow-up period of 7.0 years . Bone density was measured at three WHI centers . RESULTS Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group ( P<0.01 ) . Intention-to-treat analysis indicated that participants receiving calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture ( 95 percent confidence interval , 0.72 to 1.08 ) , 0.90 for clinical spine fracture ( 0.74 to 1.10 ) , and 0.96 for total fractures ( 0.91 to 1.02 ) . The risk of renal calculi increased with calcium plus vitamin D ( hazard ratio , 1.17 ; 95 percent confidence interval , 1.02 to 1.34 ) . Censoring data from women when they ceased to adhere to the study medication reduced the hazard ratio for hip fracture to 0.71 ( 95 percent confidence interval , 0.52 to 0.97 ) . Effects did not vary significantly according to prer and omization serum vitamin D levels . CONCLUSIONS Among healthy postmenopausal women , calcium with vitamin D supplementation result ed in a small but significant improvement in hip bone density , did not significantly reduce hip fracture , and increased the risk of kidney stones . ( Clinical Trials.gov number , NCT00000611 . ) Introduction Rheumatoid arthritis ( RA ) is one of the most prevalent autoimmune diseases worldwide . Some research ers have suggested that the serum vitamin D ( Vit D ) level may relate to disease activity . The current study was design ed to identify the correlation between vitamin D prescription and prevention of relapses in rheumatoid arthritis . Patients and method A double blinded , r and omized controlled trial study was performed using 80 RA patients . RA was controlled and patients were in remission during the past 2 months . Serum level of  Vit D  in the studied patients was below 30 ng/dl . Patients were r and omly allocated to receive Vit D or placebo . In the 6-month follow-up period , the Disease Activity Score 28 ( DAS28 ) was used in case of relapses as an index of RA activity to compare the two groups . Results The flare rate was not different between two groups ( p > 0.05 ) . The odds ratio of the rate of decline in patients of the trial group compared with the control group was 1.17 ( not significant ; p > 0.05 ) . The mean DAS28 between the two patient groups was not significant ( p > 0.05 ) . Conclusion A low Vit D level was not identified to be a risk factor for RA severity or flare ups ; however , although not statistically significant , Vit D treatment might be clinical ly effective . Further studies are needed with more emphasis on the issue of cost effectiveness and clinical importance to provide more information . ZusammenfassungEinleitungDie rheumatoide Arthritis ( RA ) gehört weltweit zu den häufigsten Autoimmunerkrankungen . Manche Forscher vermuten , dass die Aktivität der Erkrankung mit dem Vitamin-D-Spiegel i m Serum zusammenhängt . In der vorliegenden Studie sollte die Beziehung zwischen der Verschreibung von Vitamin D und der Prävention von RA-Rezidiven ermittelt werden . Abstract Section StopPatienten und Method enAn 80 RA-Patienten wurde eine doppelblinde , r and omisierte , kontrollierte Studie durchgeführt . Die Erkrankung war unter Kontrolle , die Patienten hatten sich in den vorausgegangenen 2 Monaten in Remission befunden . Der Serum-Vitamin-D-Spiegel lag bei den eingeschlossenen Patienten unter 30 ng/dl . Die Teilnehmer wurden in 2 Gruppen r and omisiert . Eine erhielt Vitamin D , die and ere Placebo . I m 6-monatigen Follow-up wurde i m Falle eines Rezidivs der Disease Activity Score 28 ( DAS28 ) herangezogen , um die beiden Gruppen bezüglich der RA-Aktivität zu vergleichen . ErgebnisseDie Gruppen unterschieden sich nicht hinsichtlich der Rate an Schüben ( p > 0,05 ) . Die Odds Ratio der Abnahme betrug für Patienten in der beh and elten Gruppe i m Vergleich zur Kontrollgruppe 1,17 ( nicht signifikant ; p > 0,05 ) . Auch hinsichtlich des durchschnittlichen DAS28 f and sich in den beiden Gruppen keine Signifikanz ( p > 0,05).SchlussfolgerungEin niedriger Vitamin-D-Spiegel erwies sich nicht als Risikofaktor für Schübe oder die Schwere der RA . Allerdings könnte die Vitamin-D-Beh and lung , wenn auch ohne statistische Signifikanz , klinisch wirksam sein . Weitere Studien mit stärkerem Gewicht auf der Kosteneffektivität und klinischen Bedeutung sind notwendig BACKGROUND Various treatments including corticosteroids , nonsteroidal anti-inflammatory drugs , D-penicillamine , interferon gamma , cyclosporine , and cytostatic drugs have been used with limited success in both morphea and systemic sclerosis ( SSc ) . OBJECTIVE We investigated the effect of treatment with oral calcitriol in patients with localized or systemic scler 
    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: Rheumatoid arthritis ( RA ) is an autoimmune disease that is characterized by chronic inflammation affecting target tissues including the joints , bones , and synovial membrane . However , the etiology and pathogenesis of RA remains to be determined , and investigations into the treatment of RA are imperative . Vitamin D ( Vit D ) was previously found to be associated with the activity of RA and exerts therapeutic benefits . The aim of the present study was to investigate the effect of Vit D on the recurrence rate of RA .  A total of 377 patients with RA at remission stage were divided into the normal Vit D group and the Vit D-deficient group according to their Vit D levels at baseline . The patients in the Vit D-deficient group were further r and omly allocated to receive treatment with or without Vit D. The patients were followed up for 24 months , and the visual analogue scale , as well as the number of pain and swelling joints were recorded every 2–3 months . In addition , C-reactive protein and the blood sedimentation rate were measured every 2–3 months to assess the recurrence of RA based on disease activity score 28 ( DAS28 ) . The recurrence rate of RA was 16.7 , 19.0 and 29.5 % for the normal Vit D group ( n=168 ) , Vit D treatment subgroup ( n=84 ) , and non-Vit D treatment subgroup ( n=88 ) , respectively . The recurrence rate of the normal Vit D group was lower , compared to the non-Vit D treatment subgroup , and the difference was statistically significant . However , the difference was not statistically significant between the Vit D treatment subgroup and non-Vit D treatment subgroup . In conclusion , a decreased level of  Vit D  is a risk factor for the recurrence of RA OBJECTIVE To identify predictors of moderate-to-severe systemic lupus erythematosus ( SLE ) flare in 562 patients treated with st and ard therapy alone in phase III belimumab trials , and to evaluate the impact of st and ard therapies on preventing flares . METHODS Post hoc analysis assessed baseline demographics , disease activity , and biomarkers in patients with and those without flare at treatment weeks 24 and 52 . Severe flare was defined by the modified SLE Flare Index ( SFI ) and the development of any new British Isles Lupus Assessment Group ( BILAG ) A domain score . Severe and moderate flare was defined by development of 1 new BILAG A domain score or 2 new BILAG B domain scores . Baseline characteristics associated with a ≥10 % absolute difference or a ≥50 % increase in flare rates were considered predictive . RESULTS Frequencies of flares over 52 weeks according to the SFI , any new BILAG A domain score , and 1 new BILAG A domain score or 2 new BILAG B domain scores were 23.7 % , 23.1 % , and 32.0 % , respectively . Flare predictors by univariate analysis on all 3 indices at weeks 24 and 52 were a score ≥12 on the Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index ( SELENA-SLEDAI ) ; anti-double-str and ed DNA ( anti-dsDNA ) positivity ; proteinuria ( ≥0.5 gm/24 hours ) ; BILAG renal , vasculitic , and hematologic scores ; elevated C-reactive protein levels ; and B lymphocyte stimulator ( BLyS ) levels ≥2 ng/ml . Independent predictors by multivariate analysis at week 52 were SELENA-SLEDAI and /or BILAG renal involvement and anti-dsDNA ≥200 IU/ml ( on all 3 indices ) ; SELENA-SLEDAI and /or BILAG neurologic and vasculitic involvement ( on 2 indices : any new BILAG A domain score and 1 new BILAG A domain score or 2 new BILAG B domain scores ) ; BLyS levels ≥2 ng/ml ( on 2 indices : the SFI and 1 new BILAG A domain score or 2 new BILAG B domain scores ) ; and low C3 level ( on the SFI ) . Baseline medications did not significantly decrease or increase moderate-to-severe SLE flare risk . CONCLUSION Patients who were receiving st and ard SLE therapy and had renal , neurologic , or vasculitic involvement , elevated anti-dsDNA or BLyS levels , or low C3 had increased risk of clinical ly meaningful flare over 1 year . Hydroxychloroquine use was not predictive To determine the efficacy of oral vitamin D [ 25(OH)D ] in patients with active rheumatoid arthritis ( RA ) who are in methotrexate ( MTX ) therapy , patients receiving stable doses of MTX  were r and omized to one of two dose groups and received 12 weeks of double-blind vitamin D[25(OH)D ] ( 50,000 IU per week ) or matching placebo . The moderate and major efficacy measure was the proportion of patients with > 0.6 and > 1.2 improvement in RA based on the Disease Activity Score 28(DAS 28 ) at 12 weeks . Safety measures included adverse events and laboratory assessment s. On a background of MTX , the percentage of patients with a moderate/major DAS 28 response at week 12 in the vitamin D groups ( 76/44 % ) was not significantly different from placebo ( 64.6/33.4 % ) . Adverse events were typically mild and included small hepatic enzyme elevation ; we did not have any undesirable events result ing in discontinuation of study drug . In patients with active RA receiving stable doses of MTX , vitamin D showed non-significant improvement in efficacy outcomes compared to placebo Objective . We determined the prevalence of and risk factors for British Isles Lupus Activity Group ( BILAG ) flare in patients with systemic lupus erythematosus ( SLE ) . Methods . We followed 299 patients for 1 year with the  BILAG scores  calculated using British Lupus Integrated Prospect i ve System software and confirmed with manual calculation . Results . “ A ” flares occurred at a rate of 0.254/year , “ B ” flares 1.637/year , and A or B flares 1.765/year . The most common A flares were renal and mucocutaneous . The most common B flares were hematologic , renal , mucocutaneous , and musculoskeletal . Risk factors for a later A or B flare in the hematological system included : low C3 ( p < 0.0001 ) , low C4 ( p = 0.0004 ) , and positive anti-double-str and ed (ds)DNA ( p = 0.003 ) ; in the mucocutaneous system : low C3 ( p = 0.02 ) and low C4 ( p = 0.0004 ) ; and in the renal system : low C3 ( p = 0.02 ) and low C4 ( p = 0.02 ) . In a stepwise regression model , only ethnicity ( p = 0.02 ) and low C4 ( p = 0.0002 ) remained as independent predictors of later A or 2B flares . Conclusion . The organ system distribution of A and B flares is very different , with A flares more common in renal and mucocutaneous , and B flares more common in hematologic and renal systems . A or 2B flares are significantly more common in African Americans and in patients with abnormal serologies ( low C3 , low C4 , or high anti-dsDNA ) . If flare is an outcome in an SLE clinical trial , these factors must be balanced by taking them into account at baseline in terms of r and omization , or by statistical adjustment in final analyses BACKGROUND The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal . METHODS We recruited 36,282 postmenopausal women , 50 to 79 years of age , who were already enrolled in a Women 's Health Initiative ( WHI ) clinical trial . We r and omly assigned participants to receive 1000 mg of elemental [ corrected ] calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo .  Fractures were ascertained for an average follow-up period of 7.0 years . Bone density was measured at three WHI centers . RESULTS Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group ( P<0.01 ) . Intention-to-treat analysis indicated that participants receiving calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture ( 95 percent confidence interval , 0.72 to 1.08 ) , 0.90 for clinical spine fracture ( 0.74 to 1.10 ) , and 0.96 for total fractures ( 0.91 to 1.02 ) . The risk of renal calculi increased with calcium plus vitamin D ( hazard ratio , 1.17 ; 95 percent confidence interval , 1.02 to 1.34 ) . Censoring data from women when they ceased to adhere to the study medication reduced the hazard ratio for hip fracture to 0.71 ( 95 percent confidence interval , 0.52 to 0.97 ) . Effects did not vary significantly according to prer and omization serum vitamin D levels . CONCLUSIONS Among healthy postmenopausal women , calcium with vitamin D supplementation result ed in a small but significant improvement in hip bone density , did not significantly reduce hip fracture , and increased the risk of kidney stones . ( Clinical Trials.gov number , NCT00000611 . ) Introduction Rheumatoid arthritis ( RA ) is one of the most prevalent autoimmune diseases worldwide . Some research ers have suggested that the serum vitamin D ( Vit D ) level may relate to disease activity . The current study was design ed to identify the correlation between vitamin D prescription and prevention of relapses in rheumatoid arthritis . Patients and method A double blinded , r and omized controlled trial study was performed using 80 RA patients . RA was controlled and patients were in remission during the past 2 months . Serum level of  Vit D  in the studied patients was below 30 ng/dl . Patients were r and omly allocated to receive Vit D or placebo . In the 6-month follow-up period , the Disease Activity Score 28 ( DAS28 ) was used in case of relapses as an index of RA activity to compare the two groups . Results The flare rate was not different between two groups ( p > 0.05 ) . The odds ratio of the rate of decline in patients of the trial group compared with the control group was 1.17 ( not significant ; p > 0.05 ) . The mean DAS28 between the two patient groups was not significant ( p > 0.05 ) . Conclusion A low Vit D level was not identified to be a risk factor for RA severity or flare ups ; however , although not statistically significant , Vit D treatment might be clinical ly effective . Further studies are needed with more emphasis on the issue of cost effectiveness and clinical importance to provide more information . ZusammenfassungEinleitungDie rheumatoide Arthritis ( RA ) gehört weltweit zu den häufigsten Autoimmunerkrankungen . Manche Forscher vermuten , dass die Aktivität der Erkrankung mit dem Vitamin-D-Spiegel i m Serum zusammenhängt . In der vorliegenden Studie sollte die Beziehung zwischen der Verschreibung von Vitamin D und der Prävention von RA-Rezidiven ermittelt werden . Abstract Section StopPatienten und Method enAn 80 RA-Patienten wurde eine doppelblinde , r and omisierte , kontrollierte Studie durchgeführt . Die Erkrankung war unter Kontrolle , die Patienten hatten sich in den vorausgegangenen 2 Monaten in Remission befunden . Der Serum-Vitamin-D-Spiegel lag bei den eingeschlossenen Patienten unter 30 ng/dl . Die Teilnehmer wurden in 2 Gruppen r and omisiert . Eine erhielt Vitamin D , die and ere Placebo . I m 6-monatigen Follow-up wurde i m Falle eines Rezidivs der Disease Activity Score 28 ( DAS28 ) herangezogen , um die beiden Gruppen bezüglich der RA-Aktivität zu vergleichen . ErgebnisseDie Gruppen unterschieden sich nicht hinsichtlich der Rate an Schüben ( p > 0,05 ) . Die Odds Ratio der Abnahme betrug für Patienten in der beh and elten Gruppe i m Vergleich zur Kontrollgruppe 1,17 ( nicht signifikant ; p > 0,05 ) . Auch hinsichtlich des durchschnittlichen DAS28 f and sich in den beiden Gruppen keine Signifikanz ( p > 0,05).SchlussfolgerungEin niedriger Vitamin-D-Spiegel erwies sich nicht als Risikofaktor für Schübe oder die Schwere der RA . Allerdings könnte die Vitamin-D-Beh and lung , wenn auch ohne statistische Signifikanz , klinisch wirksam sein . Weitere Studien mit stärkerem Gewicht auf der Kosteneffektivität und klinischen Bedeutung sind notwendig BACKGROUND Various treatments including corticosteroids , nonsteroidal anti-inflammatory drugs , D-penicillamine , interferon gamma , cyclosporine , and cytostatic drugs have been used with limited success in both morphea and systemic sclerosis ( SSc ) . OBJECTIVE We investigated the effect of treatment with oral calcitriol in patients with localized or systemic scler 
    Output:
    