Randomized Clinical Trials on the Efficacy and Safety of Tocilizumab in Subjects with Rheumatoid Arthritis: A Systematic Review.

BACKGROUND: The current therapy of Rheumatoid Arthritis (RA) is confronted with many challenges such as inadequate response, infection, and treatment failure. AIM AND OBJECTIVE: The main objective was to assess the efficacy and safety of tocilizumab (TCZ) in subjects with RA using the available evidence from published randomized controlled trials. METHODS: The current systematic review was performed on nine randomized controlled trials from 2002 to 2016 for TCZ in subjects with rheumatoid arthritis. The primary outcomes were the clinical improvement in American College Rheumatology 20% (ACR20) or Disease Activity Score remission (DAS28), in addition to other outcomes such as ACR50 and ACR70 in the intention-to-treat population. RESULTS: We have conducted a systematic review on nine randomized controlled trials, with 4129 [100%] enrolled, of which 3248 [78.7%] were on the intention-to-treat. 2147 (66.1%) were treated with TCZ and 1101 (33.9%) have had received placebo or methotrexate or other conventional Disease- Modifying Anti-rheumatic Drugs (cDMARD) or biologic Disease-Modifying Anti-rheumatic Drugs (bDMARDs). In subjects taking TCZ with or without concomitant methotrexate, compared to placebo, subjects treated with TCZ 4 or 8 mg/kg were substantially and statistically significantly more likely than placebo or methotrexate to achieve the ACR20 and/or DAS28. There were no statistically significant differences in serious adverse events such as serious infection; however, subjects on TCZ were more likely to have increased lipid profiles. CONCLUSION: TCZ mono-therapy or in combination with methotrexate is valuable in diminishing rheumatoid arthritis disease activity and improving disability. Treatment with TCZ was associated with a significant surge in cholesterol levels but no serious adverse effects. Randomized clinical trials with safety as the primary outcome are warranted to report these safety issues.

A Systematic Review of Randomized Clinical Trials on the Efficacy and Safety of Pitavastatin.

BACKGROUND: A subpopulation of statin users such as subjects with chronic kidney disease (CKD), Human Immune virus (HIV), acute coronary syndrome (ACS), revascularization, metabolic syndrome, and/or diabetes may particularly benefit from pitavastatin pharmacotherapy. AIM: The current systematic review aimed systematically to evaluate the effect of pitavastatin on primary cardiac events in subjects receiving pitavastatin in comparison to the other four statin members. METHODS: We conducted a systematic review on phases III and IV of randomized controlled trials (RCT-s, 11 trials) for subjects with primary cardiac events who received pitavastatin. Subjects diagnosed with any type of dyslipidemia (population 4804) and received pitavastatin (interventions) versus comparator (comparison) with the primary efficacy endpoint of minimization of LDL-C and non- HDL-C, had an increase in HDL-C and/or reduction in major adverse cardiac events (MACE, cardiovascular death, myocardial infarction (fatal/nonfatal), and stroke (fatal/nonfatal) and/or their composite (outcomes). The secondary safety endpoint was the development of any adverse effects. RESULTS: In the included trials (11), participants (4804) were randomized for pitavastatin or its comparators such as atorvastatin, pravastatin, rosuvastatin, simvastatin and followed up for 12 to 52 weeks. In terms of the primary outcome (reduction in LDL-C), pitavastatin 4 mg was superior to pravastatin 40 mg in three trials, while the 2 mg pitavastatin was comparable to atorvastatin 10 mg in four trials and simvastatin 20 and 40 mg in two 2 trials. However, rosuvastatin 2.5 mg was superior to pitavastatin 2 mg in two trials. Pitavastatin increased HDL-C and reduced non-HDL-C in eleven trials. Regarding the safety profile, pitavastatin has proved to be tolerated and safe. CONCLUSION: The FDA-approved indications for pitavastatin included primary dyslipidemia and mixed dyslipidemia as a supplementary therapy to dietary changes to lower total cholesterol, LDL-C, apolipoprotein B (Apo B), triglycerides (TG), and enhance HDL-C. Pitavastatin might be suitable for subjects with diabetes, ACS (reduced revascularization), metabolic syndrome, CKD, HIV, and subjects with low levels of HDL-C. We highly recommend rational individualization for the selection of statin.

Scoping Review of Six Retrospective Studies: Risk Factors Associated With the Case Fatality Rate of People Infected With Coronavirus (COVID-19).

Background: It would be rational to describe the pattern of the clinical characteristics of the survivors and the nonsurvivors during the critical intensive-infection era of coronavirus disease 2019 (COVID-19). The explicit objective of the current scoping review was to delineate the predictive risk factors associated with case fatality rate (CFR). Methods: Six retrospective studies of subjects infected with COVID-19 published between December 1, 2020, and March 30, 2020, describing nonsurvivors in Wuhan/Hubei, China, were identified. Results: There were 1769 subjects with a mean age of 52 years, and 65.9% were male. The highest comorbidity reported was cardiovascular diseases at 22.2% (393/1769). The overall number of cases admitted to the intensive care unit was 228 (12.9%). The reported overall CFR was 7.7% (136/1769), with the highest at 28.2% (54/191), and the lowest at 1.4% (15/1099). The mean duration of onset until death for nonsurvivors was 15.3 days. Conclusion: We have found that older age, male gender, the longer duration from onset till death (days), development of acute respiratory distress syndrome/shock, preexisting diabetes, and preexisting cardiovascular diseases were the major risk factors associated with high CFR.

Systematic Review of Glucagon-Like Peptide One Receptor Agonist Liraglutide of Subjects with Heart Failure with Reduced Left Ventricular Ejection Fraction.

BACKGROUND: The major cardiovascular outcome trials on glucagon-like peptide one-receptor agonists have examined its effect on hospitalization of subjects with heart failure; however, very limited trials have been conducted on subjects with reduced left ventricular ejection fraction (r- LVEF) as a primary outcome. OBJECTIVE: We have conducted a systematic review of two major (FIGHT and LIVE) placebo-controlled trials of liraglutide and its clinical effect on the ejection fraction of subjects with heart failure. METHODS: Medline data was retrieved for trials involving liraglutide from 2012 to 2020. The inclusion criteria for trials were: subjects with or without type 2 diabetes mellitus (T2DM), subjects with heart failure with rLVEF, major trials (phase II or III) on liraglutide, trials included liraglutide with defined efficacy primary outcome of patients with heart failure with rLVEF. The search was limited to the English language, whereby two trials [FIGHT and LIVE] had been included and two trials were excluded due to different primary outcomes. Participants (541) had been randomized for either liraglutide or placebo for 24 weeks. RESULTS: In the FIGHT trial the primary intention-to-treat, sensitivity, and diabetes subgroup analyses have shown no significant between-group difference in the global rank scores (mean rank of 146 in the liraglutide group versus 156 in the placebo group; Wilcoxon rank-sum P=.31), number of deaths, re-hospitalizations for heart failure, or the composite of death or change in NT-pro BNP level (P= .94). In the LIVE trial, the change in the left ventricular ejection fraction (LVEF) from baseline to week 24 was not significantly different between treatment groups. The overall discontinuation rate of liraglutide was high in the FIGHT trial (29%, 86) as compared to that in the LIVE trial (11.6%, 28). CONCLUSION: FIGHT and LIVE trials have demonstrated that liraglutide use in subjects with heart failure and rLVEF was implicated with an increased adverse risk of heart failure-related outcomes.

The early mortality rate of people infected with coronavirus (COVID-2019) in Wuhan, China: Review of three retrospective studies.

BACKGROUND: The infection with coronavirus and non-survivor cases have been escalated since the first inception between January and March 2020. Therefore, reviewing the collated clinical characteristics of non-survivors might assist in current preventive efforts, triaging, and management of survivors. The aim of this review was to summarize the clinical characteristics of non-survivor cases due to the infection caused by a novel coronavirus and to identify the relevant data that might put the new cases at increased mortality. MATERIALS AND METHODS: We have identified three published articles on novel coronavirus reported during December 01, 2020, to March 15, 2020, which have described the mortality rate in Wuhan, Hubei, China. RESULTS: The mean duration of studies (i.e., the three retrospective studies with 278 cases) was 24.7 days, and the duration of onset to dyspnea was variable between 8 and 5 days. The main reported complications were acute respiratory distress, pneumonia, acute kidney injury, and acute cardiac disease. The overall major comorbidity reported was cardiovascular diseases at 23.7% (66 of 278). The reported overall mortality rate was 8.3% (23 of 278), with the highest mortality rate of 15.0% (6 of 41) reported in Jin Yintan Hospital at Wuhan city. CONCLUSIONS: The clinical characteristics of the non-survivors from the novel coronavirus included adult males, aged older than 50 years, having comorbidities of cardiovascular disease, respiratory distress syndrome, acute kidney injury, and diabetes with higher admission to the intensive care unit. The mortality rate was high in two of the reported studies (15.0% and 11.0%), which was decreased in the later-dated study to 3.4%.