You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.



Title 1:
Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants
Abstract 1:
We have genotyped 14,436 nonsynonymous SNPs ( nsSNPs ) and 897 major histocompatibility complex ( MHC ) tag SNPs from 1,000 independent cases of ankylosing spondylitis ( AS ) , autoimmune thyroid disease ( AITD ) , multiple sclerosis ( MS ) and breast cancer ( BC ) . Comparing these data against a common control data set derived from 1,500 r and omly selected healthy British individuals , we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis , ARTS1 and IL23R , and confirmation of the previously reported association of AITD with TSHR and FCRL3 . These findings , enabled in part by increased statistical power result ing from the expansion of the control reference group to include individuals from the other disease groups , highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major ' seronegative ' diseases


Title 2:
Infliximab in spondyloarthropathy associated with Crohn's disease: an open study on the efficacy of inducing and maintaining remission of musculoskeletal and gut manifestations.
Abstract 2:
OBJECTIVE To evaluate the efficacy and tolerability of anti-tumour necrosis factor alpha ( TNFalpha ) monoclonal antibody ( infliximab ) in the treatment of spondyloarthropathy ( SpA ) associated with active and inactive Crohn 's disease ( CD ) . METHODS Twenty four patients with SpA associated with active or inactive CD ( 16 active , 8 quiescent ) were treated with anti-TNFalpha monoclonal antibody ( infliximab ) with repeated infusions for a period of 12 - 18 months . The treatment aim ed at ameliorating the general musculoskeletal and spinal pain , controlling peripheral arthritis and enthesitis , decreasing the BASDAI score , modifying acute phase reactants , and reducing CD activity . RESULTS Infliximab improved both gastrointestinal ( p<0.01 ) and overall articular symptoms ( BASDAI , p<0.01 ; general musculoskeletal and spinal pain , p<0.01 ; peripheral arthritis , p<0.01 ) in patients with active CD . Additionally , infliximab effectively controlled not only axial involvement and peripheral arthritis but also enthesitis ( p<0.01 ) and prevented inflammatory bowel disease reactivation in patients with inactive CD and low inflammatory markers . Amelioration of gut and musculoskeletal involvement persisted for up to 12 months . CONCLUSION Infliximab may act on the inflammation of entheses and of periarticular structures , which usually does not cause a change in the haematological markers that are the main indicators of pain and joint ankylosis in SpA. Infliximab induces and maintains remission of CD while at the same time treating active and severe SpA , suggesting that it should be the preferred drug for the treatment of active and severe SpA associated with active or quiescent CD


Title 3:
An expansion of rare lineage intestinal microbes characterizes rheumatoid arthritis
Abstract 3:
Background The adaptive immune response in rheumatoid arthritis ( RA ) is influenced by an interaction between host genetics and environment , particularly the host microbiome . Association of the gut microbiota with various diseases has been reported , though the specific components of the microbiota that affect the host response leading to disease remain unknown . However , there is limited information on the role of gut microbiota in RA . In this study we aim ed to define a microbial and metabolite profile that could predict disease status . In addition , we aim ed to generate a humanized model of arthritis to confirm the RA-associated microbe . Methods To identify an RA biomarker profile , the 16S ribosomal DNA of fecal sample s from RA patients , first-degree relatives ( to rule out environment/ background as confounding factors ) , and r and om healthy non-RA controls were sequenced . Analysis of metabolites and their association with specific taxa was performed to investigate a potential mechanistic link . The role of an RA-associated microbe was confirmed using a human epithelial cell line and a humanized mouse model of arthritis . Results Patients with RA exhibited decreased gut microbial diversity compared with controls , which correlated with disease duration and autoantibody levels . A taxon-level analysis suggested an expansion of rare taxa , Actinobacteria , with a decrease in abundant taxa in patients with RA compared with controls . Prediction models based on the r and om forests algorithm suggested that three genera , Collinsella , Eggerthella , and Faecalibacterium , segregated with RA . The abundance of Collinsella correlated strongly with high levels of alpha-aminoadipic acid and asparagine as well as production of the proinflammatory cytokine IL-17A . A role for Collinsella in altering gut permeability and disease severity was confirmed in experimental arthritis . Conclusions These observations suggest dysbiosis in RA patients result ing from the abundance of certain rare bacterial lineages . A correlation between the intestinal microbiota and metabolic signatures could determine a predictive profile for disease causation and progression


Title 4:
A longitudinal study of fecal calprotectin and the development of inflammatory bowel disease in ankylosing spondylitis
Abstract 4:
Background Patients with ankylosing spondylitis ( AS ) are at increased risk of developing inflammatory bowel disease ( IBD ) . We aim ed to determine the variation in fecal calprotectin in AS over 5 years in relation to disease activity and medication and also to study the incidence of and predictors for development of IBD . Methods  Fecal calprotectin  was assessed at baseline ( n = 204 ) and at 5-year follow-up ( n = 164 ) . The patients answered question naires and underwent clinical evaluations . At baseline and at 5-year follow-up , ileocolonoscopy was performed in patients with fecal calprotectin ≥500 mg/kg and ≥200 mg/kg , respectively . The medical records were checked for diagnoses of IBD during the follow-up period . Results Fecal calprotectin > 50 mg/kg was found in two-thirds of the patients at both study visits . In 80 % of the patients , fecal calprotectin changed by < 200 mg/kg between the two measuring points . Baseline fecal calprotectin was positively correlated with Ankylosing Spondylitis Disease Activity Score based on C-reactive protein , Bath Ankylosing Spondylitis Disease Activity Index , Bath Ankylosing Spondylitis Functional Index , C-reactive protein , erythrocyte sedimentation rate , and fecal calprotectin at 5-year follow-up . The use of nonsteroidal anti-inflammatory drugs ( NSAIDs ) was associated with higher fecal calprotectin , and 3-week cessation of NSAIDs result ed in a drop of a median 116 mg/kg in fecal calprotectin . The use of tumor necrosis factor ( TNF ) blockers was associated with lower fecal calprotectin at both visits , but the users of TNF receptor fusion proteins had significantly higher fecal calprotectin than users of anti-TNF antibodies at 5-year follow-up . The 5-year incidence of Crohn ’s disease ( CD ) was 1.5 % and was predicted by high fecal calprotectin . Conclusions Fecal calprotectin was elevated in a majority of the patients and was associated with disease activity and medication at both visits . CD developed in 1.5 % of the patients with AS , and a high fecal calprotectin was the main predictor thereof . The results support a link between inflammation in the gut and the musculoskeletal system in AS . We propose that fecal calprotectin may be a potential biomarker to identify patients with AS at risk of developing IBD.Trial registration Clinical Trials.gov identifier : NCT00858819 . Registered 9 March 2009 . Last up date d 28 May 2015


Title 5:
The assessment of faecal flora in patients with inflammatory bowel disease by a simplified bacteriological technique.
Abstract 5:
A semi-quantitative bacteriological method was used to study faecal flora in 42 patients with Crohn 's disease , 37 with ulcerative colitis and 21 healthy controls . Faecal homogenates were plated on primary isolation plates by a technique that allowed the growth of various microbial isolates to be assessed on a visual 1(+)-5 + score . This method was first calibrated against a st and ard quantitative bacteriological technique , which confirmed the reliability and reproducibility of the results obtained by the simpler method . Patients with clinical ly active Crohn 's disease ( 22 ) had significantly higher total aerobe scores than patients with quiescent disease ( 20 ) ( p less than or equal to 0.006 ) or ulcerative colitis ( p less than or equal to 0.04 ) or normal controls ( p less than or equal to 0.02 ) . The scores of Escherichia coli were parallel to those of total aerobes . Lactobacillus and bifidobacteria scores were significantly reduced in patients with Crohn 's disease compared to those with ulcerative colitis and controls . The anaerobic flora in both Crohn 's disease and ulcerative colitis was indistinguishable from that of controls . Bacteroides vulgatus and B. fragilis were the predominant bacteroides in all groups . Patients with ulcerative colitis , regardless of disease activity , harboured faecal flora that did not differ from that of normal controls . The abnormal faecal flora in Crohn 's disease did not correlate with established clinical and laboratory indicators of disease activity


Title 6:
Alterations in the gut microbiome of children with severe ulcerative colitis
Abstract 6:
Background : Although the role of microbes in disease pathogenesis is well established , data describing the variability of the vast microbiome in children diagnosed with ulcerative colitis ( UC ) are lacking . This study characterizes the gut microbiome in hospitalized children with severe UC and determines the relationship between microbiota and response to steroid therapy . Methods : Fecal sample s were collected from 26 healthy controls and 27 children hospitalized with severe UC as part of a prospect i ve multicenter study . DNA extraction , polymerase chain reaction ( PCR ) amplification of bacterial 16S rRNA , and microarray hybridization were performed . Results were analyzed in GeneSpring GX 11.0 comparing healthy controls with children with UC , and steroid responsive ( n = 17 ) with nonresponsive patients ( n = 10 ) . Results : Bacterial signal strength and distribution showed differences between UC and healthy controls ( adjusted P < 0.05 ) for Phylum , Class , Order , Family , Genus , and Phylospecies levels with reduction in Clostridia and an increase in Gamma‐proteobacteria . The number of microbial phylospecies was reduced in UC ( 266 ± 69 ) vs. controls ( 758 ± 3 , P < 0.001 ) , as was the Shannon Diversity Index ( 6.1 ± 0.23 vs. 6.49 ± 0.04 , respectively ; P < 0.0001 ) . Steroid nonresponders harbored fewer phylospecies than responders ( 142 ± 49 vs. 338 ± 62 , P = 0.013 ) . Conclusions : Richness , evenness , and biodiversity of the gut microbiome were remarkably reduced in children with UC compared with healthy controls . Children who did not respond to steroids harbored a microbiome that was even less rich than steroid responders . This study is the first to characterize the gut microbiome in a large cohort of pediatric patients with severe UC and describes changes in the gut microbiome as a potential prognostic feature . ( Inflamm Bowel Dis 2012


Title 7:
Comparison of sulfasalazine and placebo in the treatment of psoriatic arthritis. A Department of Veterans Affairs Cooperative Study.
Abstract 7:
OBJECTIVE To determine whether sulfasalazine ( SSZ ) at a dosage of 2,000 mg/day is effective for the treatment of active psoriatic arthritis ( PsA ) resistant to nonsteroidal antiinflammatory drug therapy . METHODS Two hundred twenty-one patients with PsA were recruited from 15 clinics , r and omized ( double-blind ) to SSZ or placebo treatment , and followed up for 36 weeks . Treatment response was based on joint pain/ tenderness and swelling scores and physician and patient global assessment s. RESULTS Longitudinal analysis revealed a trend favoring SSZ treatment ( P = 0.13 ) . At the end of treatment , response rates were 57.8 % for SSZ compared with 44.6 % for placebo ( P = 0.05 ) . The Westergren erythrocyte sedimentation rate declined more in the PsA patients taking SSZ than in those taking placebo ( P < 0.0001 ) . Adverse reactions were fewer than expected and were mainly due to nonspecific gastrointestinal complaints , including dyspepsia , nausea , vomiting , and diarrhea . CONCLUSION SSZ at a dosage of 2,000 mg/day is well tolerated and may be more effective than placebo in the treatment of patients with


Title 8:
Results from the 2nd Scientific Workshop of the ECCO. I: Impact of mucosal healing on the course of inflammatory bowel disease.
Abstract 8:
Over the past years , mucosal healing has emerged as a major therapeutic goal in clinical trials in inflammatory bowel diseases . Accumulating evidence indicates that mucosal healing may change the natural course of the disease by decreasing the need for surgery and reducing hospitalization rates in both ulcerative colitis and Crohn 's disease . Mucosal healing may also prevent the development of long-term disease complications , such as bowel damage in Crohn 's disease and colorectal cancer in ulcerative colitis . Histologic healing may be the ultimate therapeutic goal in ulcerative colitis , whereas its impact on the course of Crohn 's disease is unknown . Complete mucosal healing may be required before considering drug withdrawal . Targeting early Crohn 's disease is more effective than approaches aim ed at healing mucosa in longst and ing disease . Several questions remain to be answered : should mucosal healing be systematic ally used in clinical practice ? Should we optimize therapies to achieve mucosal healing ? What is the degree of intestinal healing that is required to change the disease course ? Large prospect i ve studies addressing these issues are needed
Overall , this systematic review indicates that an increase in Bifidobacterium , Staphylococcus , Enterococcus , Lactobacillus , Pseudomonas , Klebsiella and Proteus genera , as well as a decrease in Faecalibacterium , Roseburia genera and species belonging to Verrucomicrobia and Fusobacteria phyla are common features in IBD and CRD patients , whereas dozens of bacterial species are specific features of CRD and IBD .