Comparative of the Effectiveness and Safety of Biological Agents, Tofacitinib, and Fecal Microbiota Transplantation in Ulcerative Colitis: Systematic Review and Network Meta-Analysis.

BACKGROUND: Biological agents are commonly used for the treatment of ulcerative colitis (UC). As new treatments, tofacitinib, and fecal microbiota transplantation (FMT) have demonstrated efficacy in treating UC. This network meta-analysis aims to determine the efficacy and safety of biological agents, tofacitinib, and FMT. METHODS: A network meta-analysis was conducted by systematically searching the PubMed, Embase, and Cochrane Libraries. According to strict inclusion and exclusion criteria, we included randomized controlled trials (RCTs) of biological agents, tofacitinib, and FMT in UC. A random-effect model was chosen by the network meta-analysis and sensitivity analysis. Heterogeneity test and publication bias test were performed to determine the efficacy of treatments. RESULTS: Data were extracted from 16 RCTs and we found that all treatments were more effective than the placebos. A total of 21 comparisons were made to determine efficiency. We found that infliximab, vedolizumab, and FMT performed better curative effect in terms of absolute effects and relative ranks. Furthermore, there was no statistical difference in the efficacy of biological agents, tofacitinib, and FMT. Moreover, no treatments were found to increase the occurrence of adverse events when compared with placebos, except infliximab. However, vedolizumab seemed to reduce the occurrence of adverse events compared with infliximab. CONCLUSION: Of the biological agents, vedolizumab and infliximab were the most effective, suggesting that biological agents are still a better choice. Nevertheless, tofacitinib and FMT may be promising alternatives with high efficacies. However, more safety and maintenance studies need to be conducted in future for the acquisition of more accurate results.Abbreviations: FMT: Fecal microbiota transplantation; UC: Ulcerative colitis; RCTs: Randomized controlled trials; IBD: Inflammatory bowel disease; CD: Crohn's disease; IBS: Irritable bowel syndrome; CDI: Clostridium difficile infections; ITT: Intention-to-treat; RR: Relative risk; CI: Confidence interval; CrI: Credible intervals; IFX: Infliximab; ADA: Adalimumab; TFB: Tofacitinib; GLM: Golimumab; VDZ: Vedolizumab; PBO: Placebo; wk: week; F: Female; M: Male; AEs: Adverse events; SAEs: Serious adverse events; anti-TNF: Anti-tumor necrosis factors.

Predictors for diabetic retinopathy progression-findings from nominal group technique and Evidence review.

OBJECTIVES: Risk stratification is needed for patients referred to hospital eye services by Diabetic Eye Screening Programme UK. This requires a set of candidate predictors. The literature contains a large number of predictors. The objective of this research was to arrive at a small set of clinically important predictors for the outcome of the progression of diabetic retinopathy (DR). They need to be evidence based and readily available during the clinical consultation. METHODS AND ANALYSIS: Initial list of predictors was obtained from a systematic review of prediction models. We sought the clinical expert opinion using a formal qualitative study design. A series of nominal group technique meetings to shorten the list and to rank the predictors for importance by voting were held with National Health Service hospital-based clinicians involved in caring for patients with DR in the UK. We then evaluated the evidence base for the selected predictors by critically appraising the evidence. RESULTS: The source list was presented at nominal group meetings (n=4), attended by 44 clinicians. Twenty-five predictors from the original list were ranked as important predictors and eight new predictors were proposed. Two additional predictors were retained after evidence check. Of these 35, 21 had robust supporting evidence in the literature condensed into a set of 19 predictors by categorising DR. CONCLUSION: We identified a set of 19 clinically meaningful predictors of DR progression that can help stratify higher-risk patients referred to hospital eye services and should be considered in the development of an individual risk stratification model. STUDY DESIGN: A qualitative study and evidence review. SETTING: Secondary eye care centres in North East, Midlands and South of England.

Microbe-metabolite-host axis, two-way action in the pathogenesis and treatment of human autoimmunity.

The role of microorganism in human diseases cannot be ignored. These microorganisms have evolved together with humans and worked together with body's mechanism to maintain immune and metabolic function. Emerging evidence shows that gut microbe and their metabolites open up new doors for the study of human response mechanism. The complexity and interdependence of these microbe-metabolite-host interactions are rapidly being elucidated. There are various changes of microbial levels in models or in patients of various autoimmune diseases (AIDs). In addition, the relevant metabolites involved in mechanism mainly include short-chain fatty acids (SCFAs), bile acids (BAs), and polysaccharide A (PSA). Meanwhile, the interaction between microbes and host genes is also a factor that must be considered. It has been demonstrated that human microbes are involved in the development of a variety of AIDs, including organ-specific AIDs and systemic AIDs. At the same time, microbes or related products can be used to remodel body's response to alleviate or cure diseases. This review summarizes the latest research of microbes and their related metabolites in AIDs. More importantly, it highlights novel and potential therapeutics, including fecal microbial transplantation, probiotics, prebiotics, and synbiotics. Nonetheless, exact mechanisms still remain elusive, and future research will focus on finding a specific strain that can act as a biomarker of an autoimmune disease.

Barriers and facilitators to preventive interventions for the development of obstetric fistulas among women in sub-Saharan Africa: a systematic review.

BACKGROUND: Obstetric fistula is a debilitating childbearing injury that results from poorly managed obstructed labour, leading to the development of holes between the vagina and bladder and/or rectum. Effects of this injury are long-lasting, as women become incontinent and are often marginalised from their communities. Despite continuous occurrence of this injury in lower-income countries, it is preventable, as evidenced in high-income countries. This systematic review aims to identify and understand barriers and facilitators to interventions aimed at the prevention of obstetric fistulas in sub-Saharan African women. METHODS: Electronic databases and grey literature were searched. We included studies written in English that discussed interventions to prevent obstetric fistulas implemented in sub-Saharan Africa, and their associated barriers and facilitators. Quality of the studies was assessed, and data including: country of implementation, preventive interventions, and barriers and facilitators to the interventions were extracted. They were then categorised based on the Three Phase Delay Model. RESULTS: Our search yielded 537 studies, of which 18 were included from sub-Saharan countries including Ethiopia, Nigeria, and Zambia. The most noted barrier to prevention addressed the first phase of delay: the decision to seek care, particularly lack of awareness of the dangers of unsupervised labours. The most noted facilitator addressed the decision to seek care and the quality of care received at a facility, through partnerships between health facilities and governments, and other organisations that provided both financial and resource support. CONCLUSION: Despite being categorised by the three phases of the delay model, barriers and facilitators were found to play a role in multiple phases. The topic of obstetric fistula needs to be researched more extensively, particularly the effectiveness of preventive interventions.

Obstetric Fistula: A Narrative Review of the Literature on Preventive Interventions in sub-Saharan Africa.

Obstetric fistulas are childbearing injuries that present a major public health issue, especially in the developing context. This study brings together the literature on the causes of these injuries in sub-Saharan Africa, as well as suggested interventions aimed at its prevention. Furthermore, it also aims to identify gaps in the research that need to be addressed. A systematic search of PubMed, Embase, Web of Science, and Scopus identified that extensive research has been carried out on the factors causing this injury, the main factors being complications during labour, three phases of delay, and culture. Nonetheless, there remains a dearth of literature detailing preventive measures. While few studies discussed preventive interventions that had been implemented, the literature does well to suggested preventive interventions. Suggested preventive measures target the community, as well as healthcare facilities. The literature also highlights the need for increased governmental support, as a means of preventing the development of fistulas. Using narrative review methods, we identify that the research focus remains primarily on the causes of obstetric fistula and ways of managing the injury, while paying less attention to means of preventing this injury. We therefore recommend further exploration of preventive measures.