Anti-TNF Alpha and Risk of Lymphoma in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis.

Background and Objectives: Anti-tumor necrosis factor-alpha (TNF-α) agents are effective in treating rheumatoid arthritis (RA) but may entail a risk of lymphoma due to TNF-α's role in immune surveillance. This systematic review and meta-analysis assesses the risk of lymphoma in patients with RA treated with anti-TNF agents versus patients treated with methotrexate and/or a placebo. Materials and Methods: The Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Embase, PubMed, and Google Scholar were systematically searched for relevant literature. Data were extracted and analyzed to determine risk ratios (RRs) and 95% confidence intervals (CIs), with heterogeneity assessed using I2 statistics. Methodological quality and risk of bias were assessed using the Cochrane Risk of Bias tool for randomized controlled trials (RCTs) and the Newcastle-Ottawa Scale for observational studies. Results: The search yielded 932 articles, 13 of which were retained for qualitative review and 12 for quantitative synthesis. Overall, the studies reviewed included 181,735 participants: 3772 from six RCTs and 177,963 from seven observational studies. The meta-analysis of RCTs revealed no significant difference in the risk of lymphoma between patients receiving anti-TNF-α therapy and patients on conventional treatments, with an overall RR of 1.43 (95% CI: 0.32-5.16) and I2 of 0%. Conversely, observational studies showed some variability, with an overall RR of 1.43 (95% CI: 0.59-3.47) and significant heterogeneity (I2 = 95%), whereas others indicated a potentially elevated risk of lymphoma in specific subgroups but had inconsistent results. Conclusions: The systematic and meta-analysis revealed no significant difference in the risk of lymphoma for patients with RA treated with anti-TNF-α agents versus conventional therapies. However, given the limitations of the studies included, additional research is needed to validate the results and explore potential risk factors contributing to the development of lymphoma in patients with RA.

Alterations in Skeletal Muscle Insulin Signaling DNA Methylation: A Pilot Randomized Controlled Trial of Olanzapine in Healthy Volunteers.

Antipsychotics are associated with severe metabolic side effects including insulin resistance; however, the mechanisms underlying this side effect are not fully understood. The skeletal muscle plays a critical role in insulin-stimulated glucose uptake, and changes in skeletal muscle DNA methylation by antipsychotics may play a role in the development of insulin resistance. A double-blind, placebo-controlled trial of olanzapine was performed in healthy volunteers. Twelve healthy volunteers were randomized to receive 10 mg/day of olanzapine for 7 days. Participants underwent skeletal muscle biopsies to analyze DNA methylation changes using a candidate gene approach for the insulin signaling pathway. Ninety-seven methylation sites were statistically significant (false discovery rate < 0.05 and beta difference between the groups of ≥10%). Fifty-five sites had increased methylation in the skeletal muscle of olanzapine-treated participants while 42 were decreased. The largest methylation change occurred at a site in the Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-Alpha (PPARGC1A) gene, which had 52% lower methylation in the olanzapine group. Antipsychotic treatment in healthy volunteers causes significant changes in skeletal muscle DNA methylation in the insulin signaling pathway. Future work will need to expand on these findings with expression analyses.

Developing and Validating Entrustable Professional Activities (EPAs) for Rheumatology Fellowship Training Programs in Saudi Arabia: A Delphi Study.

Background: Entrustable professional activities (EPAs) define the core tasks that a graduating rheumatologist needs to perform independently in practice. The objective of this study was to develop and validate EPAs for rheumatology fellowship training programs in Saudi Arabia. Methods: Experts met to develop an initial set of potential end-of-training EPAs by conducting a comprehensive literature review of EPAs and studying the Saudi rheumatology fellowship curriculum. Then, to validate the EPAs, we conducted two rounds of the modified Delphi technique among rheumatology experts in Saudi Arabia. A response rate of 80% was considered and the minimum number of experts needed to be 25 to 30. Descriptive statistics were utilized to describe participants' demographic characteristics and group responses to each statement in all rounds. The experts were asked to rate the relevancy of each EPA using a 5-point Likert scale in both Delphi rounds. Results: In the preliminary phase, four rheumatologists developed an initial set of 36 core EPAs for rheumatology training program in Saudi Arabia. For the two-rounds Delphi techniques, 32 experts were invited to complete the study. The response rate of the first and second round were, 78.12% (25) and 93.75% (30), respectively. The first-round Delphi resulted in a robust consensus on 31 EPAs for rheumatology training. Five EPAs were excluded, and one new EPA was proposed. In the subsequent round, all 32 EPAs achieved strong consensus. The eliminated EPAs likely fell short in one or more of the following areas: relevance to rheumatology practice in Saudi Arabia, overlapping with other EPAs, or practical challenges in the implementation. Conclusion: We have developed and validated a core set of EPAs for rheumatology fellowship training programs in Saudi Arabia. Mapping and identifying milestones for these EPAs are essential steps to follow to enhance workplace curriculum development.

Public Knowledge, Awareness, Attitudes, and Practices Regarding Seizure Attacks Among People of Makkah City.

OBJECTIVES: Seizures can occur as a result of a variety of health issues. Epilepsy is a common neurological disease and it is the most prevalent cause of seizures. Epileptic patients might experience a seizure attack at any moment. The aim of this study is to assess public knowledge, awareness, attitudes, and practices toward seizure attacks among residents of Makkah city. METHODS: A cross-sectional study was conducted utilizing an online questionnaire, which was distributed through various social media platforms. The questionnaire consisted of five parts, taking sociodemographic characteristics into consideration, and evaluating knowledge, awareness, attitudes, and practices among the general population of Makkah city. RESULTS: A total of 401 participants completed the study questionnaire: 280 (69.8%) participants were females and 121 (30.2%) were males. Overall knowledge regarding epilepsy among the study participants was evaluated. A total of 132 (32.9%) participants had a good level of knowledge, while 269 (67.1%) exhibited poor knowledge. In addition, students had significantly better knowledge (44.7%) than individuals who were employed, retired, or unemployed (27.7%), (P=.004). Furthermore, participants who had previously heard about epilepsy were more knowledgeable (34.3%) than those who had not (P =.041). Additionally, participants who attended a course on seizure control (46.7%) had significantly better knowledge than those who did not (31.2%), (P=.037). CONCLUSION: This study revealed that most of our sample of Makkah city residents had poor overall knowledge of epilepsy and seizure attacks. A health education program and awareness campaigns could help improve this lack of knowledge in Makkah city.