Optimal drug regimens for improving ALP biochemical levels in patients with primary biliary cholangitis refractory to UDCA: a systematic review and Bayesian network meta-analysis.

BACKGROUND: Up to 40% of UDCA-treated patients do not have an adequate clinical response. Farnesoid X receptor agonists, peroxisome proliferator-activated receptor agonists, and fibroblast growth factor 19 analogs were developed as adjunctive therapy. The aim of this network meta-analysis was to compare the efficacy of these drugs as add-on therapy for patients with primary biliary cholangitis (PBC) refractory to UDCA in improving ALP levels. METHODS: We searched PubMed, Embase, Web of Science, and the Cochrane Library for eligible studies until 1 December 2023. Randomized controlled trials, cohort studies, and case-control studies comparing the efficacy of different combination treatments and UDCA monotherapy in UDCA-refractory PBC patients were included in the analysis. Cumulative probability was used to rank the included treatments. RESULTS: A total of 23 articles were eligible for our network meta-analysis. In terms of improving ALP levels, In terms of improving ALP biochemical levels, bezafibrate combined with UDCA (MD 104.49, 95% CI 60.41, 161.92), fenofibrate combined with UDCA (MD 87.81, 95% CI (52.34, 129.79), OCA combined with UDCA (MD 65.21, 95% CI 8.99, 121.80), seladelpar combined with UDCA (MD 117.39, 95% CI 19.97, 213.95), elafibranor combined with UDCA (MD 140.73, 95% CI 74.34, 209.98), saroglitazar combined with UDCA (MD 132.09, 95% CI 13.99, 247.04) was more effective than UDCA monotherapy. Elafibranor in combination with UDCA was the most likely (32%) to be the optimal drug regimen. CONCLUSION: As second-line therapy for UDCA-refractory PBC, PPAR agonists were more effective than any other drugs with other mechanisms in improving ALP biochemical levels, with elafibranor being the best.

Factors associated with medical students' self-regulated learning and its relationship with clinical performance: a cross-sectional study.

BACKGROUND: The importance of self-regulated learning (SRL) has been broadly recognised by medical education institutions and medical professionals. Self-regulated learning, which is a context-specific process, is affected by personal, contextual and social factors. Although many studies on exploring the factors that influenced SRL and the relationship of between SRL and clinical achievement levels have been carried out in western countries, little is known about the factors associated with self-regulated learning and its relationship with clinical performance among medical students in China. METHODS: A cross-sectional online survey was distributed to 3rd year clinical medicine students who were in the clinical clerkship stage in a medical college in Wuhan. We used Self-regulated Learning Scale for Undergraduates (SLSU) to measure the self-regulated learning of students and Objective Structured Clinical Examination (OSCE) in the national proficiency test to assess the clinical performance of students. The participation rate was 73.95% (193 students). An independent t-test and analysis of variance were used to analyse the factors associated with self-regulated learning. The relationship between self-regulated learning and clinical performance was analysed with multilinear regression analysis. RESULTS: Univariate analysis showed that having a clear career planning and a professional idol, providing full-time teaching clinical teachers in the clerkship department and seeking the help of the surrounding classmates and the guidance of teachers or senior students were significant predictors of self-regulated learning. Multilinear regression analysis has revealed a positive relationship among extrinsic goals (partial r = 0.171), clinical clerkship evaluation (partial r = 0.197) and clinical performance (F = 4.070, p = 0.004). CONCLUSIONS: Motivation-related personal and social factors related to clinical context could promote the SRL level of medical students in China. Extrinsic goals and clinical clerkship evaluation could facilitate students' clinical achievements on clinical skills. External support, such as clinical clerkship management, might improve clinical performance on clinical skills in clinical clerkship context.

Monitoring frequency of interferon gamma release assay for tuberculosis surveillance following infliximab therapy in patients with Crohn's disease.

OBJECTIVE: To characterize the pattern of positive conversion of interferon gamma release assay (IGRA) in patients with Crohn's disease (CD) during infliximab therapy in China, which has a high burden of tuberculosis. METHODS: Eligible patients with CD who received serial IGRA screening during infliximab therapy from January 2015 to March 2020 were retrospectively included. The positive conversion rate of IGRA and the risk of subsequent tuberculosis of the patients were analyzed. RESULTS: A total of 128 patients with CD were included, and the median time from the initiation of IFX treatment to positive conversion or the last follow-up test of IGRA was 43.6 weeks. At baseline 3.9% of the patients were positive for IGRA and received prophylactic anti-tuberculosis treatment. In the other 123 patients with negative IGRA at baseline, 6.5% had IGRA positive conversion during infliximab treatment, and one (12.5%) who was exposed to Mycobacterium tuberculosis was diagnosed as having active tuberculosis. The conversion rate at 40 weeks, 2 years and 3 years after treatment were 10.0% (6/60), 2.2% (1/46) and 5.9% (1/17), respectively. Age, sex, history of smoking and alcohol consumption, disease severity (Crohn's disease activity index score) and immunosuppressive therapy were not significantly associated with latent tuberculosis test conversion. CONCLUSIONS: Positive conversion of IGRA occurs early during treatment with infliximab for CD and the monitoring frequency of IGRA should be appropriately increased at the early stage of treatment. Physicians should pay attention to patient's history of tuberculosis exposure and carry out surveillance in a timely fashion.

Pooled analysis of the comparative efficacy between tacrolimus and infliximab for ulcerative colitis.

BACKGROUND: Acute moderate-to-severe steroid-refractory ulcerative colitis (UC) has a poor prognosis and requires optimal rescue therapy. A pooled analysis was conducted to assess tacrolimus and infliximab (IFX) as rescue agents in patients with moderate-to-severe and steroid-refractory UC. METHODS: A literature search identified studies that investigated tacrolimus and IFX in moderate-to-severe steroid-refractory patients with UC. The primary outcome was short-term clinical response to treatment, including the remission and response rates. Secondary outcomes included the rates of colectomy at 3 months and adverse events rate. RESULTS: A total of 6 studies comprising 438 cases were eligible for inclusion. The pooled analysis showed that the short-term clinical response rate, clinical remission rate, and 3-month colectomy rate were 72.1%, 52.4%, and 10.1%, respectively, for those receiving tacrolimus, and 76.9%, 48.8%, and 12.4%, respectively, for those receiving IFX. No significant difference was, however, seen for tacrolimus compared with IFX with regard to clinical remission rate (odds ratio [OR] =1.08, 95% confidence interval [CI] = 0.77-1.49, P = .67), clinical response rate (OR = 0.92, 95% CI = 0.63-1.34, P = .66), and 3-month colectomy rate (OR = 0.86, 95% CI = 0.39-1.93, P = .72). More adverse events were, however, observed in the Tac group (OR = 2.16, 95% CI = 1.25-3.76, P = .006). CONCLUSIONS: Our meta-analysis suggested that both tacrolimus and IFX appeared to be effective and safe for the rescue therapy of moderate-to-severe active UC and steroid-refractory UC. Therefore, tacrolimus is another choice for these patients.