Efficacy of anti-CD3 monoclonal antibodies in delaying the progression of recent-onset type 1 diabetes mellitus: A systematic review, meta-analyses and meta-regression.

AIM: Type 1 diabetes mellitus is widely recognized as a chronic autoimmune disease characterized by the pathogenic destruction of beta cells, resulting in the loss of endogenous insulin production. Insulin administration remains the primary therapy for symptomatic treatment. Recent studies showed that disease-modifying agents, such as anti-CD3 monoclonal antibodies, have shown promising outcomes in improving the management of the disease. In late 2022, teplizumab received approval from the US Food and Drug Administration (FDA) as the first disease-modifying agent for the treatment of type 1 diabetes. This review aims to evaluate the clinical evidence regarding the efficacy of anti-CD3 monoclonal antibodies in the prevention and treatment of type 1 diabetes. METHODS: A comprehensive search of PubMed, Google Scholar, Scopus and Cochrane Central Register of Controlled Trials (CENTRAL) was conducted up to December 2022 to identify relevant randomized controlled trials. Meta-analysis was performed using a random-effects model, and odds ratios with 95% confidence intervals (CIs) were calculated to quantify the effects. The Cochrane risk of bias tool was employed for quality assessment. RESULTS: In total, 11 randomized controlled trials involving 1397 participants (908 participants in the intervention arm, 489 participants in the control arm) were included in this review. The mean age of participants was 15 years, and the mean follow-up time was 2.04 years. Teplizumab was the most commonly studied intervention. Compared with placebo, anti-CD3 monoclonal antibody treatment significantly increased the C-peptide concentration in the area under the curve at shorter timeframes (mean difference = 0.114, 95% CI: 0.069 to 0.159, p = .000). Furthermore, anti-CD3 monoclonal antibodies significantly reduced the patients' insulin intake across all timeframes (mean difference = -0.123, 95% CI: -0.151 to -0.094, p < .001). However, no significant effect on glycated haemoglobin concentration was observed. CONCLUSION: The findings of this review suggest that anti-CD3 monoclonal antibody treatment increases endogenous insulin production and improves the lifestyle of patients by reducing insulin dosage. Future studies should consider the limitations, including sample size, heterogeneity and duration of follow-up, to validate the generalizability of these findings further.

Perceptions of COVID-19-related Risks and Deaths Among Health Care Professionals During COVID-19 Pandemic in Pakistan: A Cross-sectional Study.

COVID-19 is an established challenge to the health care professionals (HCPs) having physical, emotional, and psychological repercussions. We determine the perceptions of Pakistani HCPs regarding the risks and deaths related to COVID-19. A cross-sectional study was conducted among HCPs throughout Pakistan from 16th February 2021 to 6th March 2021 by disseminating an online Google questionnaire via all possible social media platforms including WhatsApp, Facebook, Twitter, and emails. Out of total of 462 HCPs, 33.55% tested COVID-19 positive and 49.43% had received their first dose of COVID-19 vaccine. The proportion of HCPs worried about contracting COVID-19 was 46.97%. A total of 69.48% mentioned that doctors are at a higher risk of dying from COVID-19 infection compared to the general population. In a dichotomous analysis done for risk perception, 72.06% of doctors reported a high-risk perception of contracting COVID-19 in hospital settings. The main reasons identified to be associated with higher mortality amongst the HCPs, specifically doctors, included comorbidities (47.26%), working in high-risk wards (24.02%) and lack of adequate personal protective equipment (PPE) (28.72%). Using univariate and multivariate regression the HCPs tested positive rated two-fold high risk while performing professional duty during COVID-19 pandemic [unadjusted odds ratio (OR) (95% confidence interval (CI)): 2.23 (1.24-4.02), P = .007; adjusted OR (95% CI) 2.27 (1.22-4.19), P = .009]. In conclusion, Pakistani HCPs have significant COVID-19-related concerns and anxieties. The doctors perceived to be at a higher risk of dying with COVID-19, due to a variety of personal and professional reasons.