Background and objectives A flare-up in coronavirus disease 2019 (COVID-19) cases threatens the health of people, and though there is no proven pharmacological treatment, many analytical studies have suggested that interleukin-6 (IL-6) levels are elevated in cases of severe COVID-19 and that the anti-IL-6 biologic agent tocilizumab may be beneficial. This is a critical review of studies aiming to assess the safety and efficacy of tocilizumab as compared to the standard regimen in patients with COVID-19. Materials and methods Online databases (PubMed and Cochrane) were searched until June 29, 2020, for original articles investigating the immunological response in COVID-19 and its treatment with tocilizumab. Data on multiple baseline characteristics and pre-specified endpoints were extracted and pooled using a random effect model. We used Review Manager version 5.3 (The Nordic Cochrane Centre, The Cochrane Collaboration, 2014, Denmark) and Stata 11.0 (Stata Corporation LP, College Station, TX) for all analyses. Risk ratios (RR) and the weighted mean difference (WMD) with the corresponding 95% confidence interval (CI) were calculated. Results From a total of 1,246 identified articles, 13 studies were included after duplicate removal and narrowing based on title and abstract. Of the 13 included studies, seven case-control studies were shortlisted for metaanalysis (quantitative) and six-single arm studies were used in the discussion (qualitative). These studies had 766 patients (351 in the tocilizumab arm and 414 in the control arm). Their pooled analysis demonstrated that mortality was significantly lower in the tocilizumab group (RR=0.56 [0.34, 0.92]; p=0.02; I 2 =76%), as was the need for artificial invasive ventilation (RR=0.34 [0.12, 0.99]; p=0.05; I 2 =0%) as compared to the control group. No significant differences were observed between tocilizumab and control group in intensive care unit admissions (RR=0.73 [0.15, 3.59]; p=0.70; I 2 =60%) and risks of post-drug infection (RR=1.29 [0.41, 4.04]; p=0.66; I 2 =88%). In terms of efficacy outcome, improved oxygen saturation (RR=1.13 [1.04, 1.65]; p=0.02; I 2 =0%) was reported to be markedly significant in tocilizumab patients when compared with the standard care group. Conclusions Our results based on pooled studies show tocilizumab to be safe and efficacious in reducing mortality among critically ill COVID-19 patients. However, due to the limited number of observational studies, the positive findings should be viewed cautiously and warrant further investigation.
Background Colchicine has been used an effective anti-inflammatory drug to treat gout diseases. Owing to its pharmacodynamic of inhibiting interleukins, it has been repurposed to target the cytokine storm post-SARS-CoV-2 invasion. The goal of this meta-analysis was to evaluate the safety profile of colchicine in COVID-19 patients using the gold-standard randomised-control trials. Methods Electronic databases (Pubmed, Google Scholar, and Cochrane) were systematically searched until June 2021 and RCTs were extracted. Outcomes of interest included all-cause mortality, COVID-19 severity, mechanical ventilation, C-reactive protein and D-dimer levels. Using a random-effects model, dichotomous outcomes were pooled using odds ratios (OR) through the generic inverse variance formula while weighted mean differences were calculated using the Wan’s method. P-values < 0.05 were considered statistically significant for all outcomes. Results A total population of 16,048 from five RCTs were included in the analysis. Of this, 7957 were randomized to colchicine, and 8091 received standard care, with an average age of 60.67 years. Colchicine was observed to significantly reduce COVID-19 severity (OR: 0.41, 95% CI [0.22, 0.76]; p = 0.005), and CRP levels (WMD: -19.99, 95% CI [-32.09, -7.89]; p = 0.001). However, there was no significant difference in D-dimer levels (WMD: 0.31, 95% CI [-0.61, 1.23]; p = 0.51), mechanical ventilation (OR: 0.42, 95% CI [0.17, 1.03]; p = 0.06; I2 = 74%) and all-cause mortality (OR: 0.98, 95% CI [0.83, 1.16]; p = 0.84) among patients receiving colchicine or standard care. Conclusion Colchicine treatment decreased CRP levels and COVID-19 severity, with dimer levels, all-cause mortality and mechanical ventilation remaining seemingly unaffected. Thus, clinical trials need to be carried out that allow effective evaluation of colchicine in COVID-19 patients.
Testosterone replacement therapy (TRT) has been used to treat hypogonadal males with type 2 diabetes mellitus (T2DM) for a long time, despite variable results. This meta-analysis examines TRT’s role in hypogonadal males with T2DM. The databases PubMed, Embase, and Google Scholar were searched for relevant RCTs and observational studies. Estimated pooled mean differences (MDs) and relative risks with 95% confidence intervals were used to measure the effects of TRT (CIs). When compared to the placebo, TRT improves glycemic management by significantly reducing glycated hemoglobin (HBA1c) levels (WMD = −0.29 [−0.57, −0.02] p = 0.04; I2 = 89.8%). Additionally, it reduces the homeostatic model assessment levels of insulin resistance (WMD = −1.47 [−3.14, 0.19]; p = 0.08; I2 = 56.3%), fasting glucose (WMD = −0.30 [−0.75, 0.15]; p = 0.19; I2 = 84.4%), and fasting insulin (WMD = −2.95 [−8.64, 2.74]; however, these results are non-significant. On the other hand, HBA1c levels are significantly reduced with TRT; in addition, total testosterone levels significantly increase with testosterone replacement therapy (WMD = 4.51 [2.40, 6.61] p = 0.0001; I2 = 96.3%). Based on our results, we hypothesize that TRT can improve glycemic control and hormone levels, as well as lower total cholesterol, triglyceride, and LDL cholesterol levels while raising HDL cholesterol in hypogonadal type 2 diabetes patients. To this end, we recommend TRT for these patients in addition to standard diabetes care.
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