Colchicine for the treatment of patients with COVID-19: an updated systematic review and meta-analysis of randomised controlled trials.

OBJECTIVES: We conducted an updated systematic review and meta-analysis to investigate the effect of colchicine treatment on clinical outcomes in patients with COVID-19. DESIGN: Systematic review and meta-analysis. DATA SOURCES: We searched PubMed, Embase, the Cochrane Library, medRxiv and ClinicalTrials.gov from inception to January 2023. ELIGIBILITY CRITERIA: All randomised controlled trials (RCTs) that investigated the efficacy of colchicine treatment in patients with COVID-19 as compared with placebo or standard of care were included. There were no language restrictions. Studies that used colchicine prophylactically were excluded. DATA EXTRACTION AND SYNTHESIS: We extracted all information relating to the study characteristics, such as author names, location, study population, details of intervention and comparator groups, and our outcomes of interest. We conducted our meta-analysis by using RevMan V.5.4 with risk ratio (RR) and mean difference as the effect measures. RESULTS: We included 23 RCTs (28 249 participants) in this systematic review. Colchicine did not decrease the risk of mortality (RR 0.99; 95% CI 0.93 to 1.05; I2=0%; 20 RCTs, 25 824 participants), with the results being consistent among both hospitalised and non-hospitalised patients. There were no significant differences between the colchicine and control groups in other relevant clinical outcomes, including the incidence of mechanical ventilation (RR 0.75; 95% CI 0.48 to 1.18; p=0.22; I2=40%; 8 RCTs, 13 262 participants), intensive care unit admission (RR 0.77; 95% CI 0.49 to 1.22; p=0.27; I2=0%; 6 RCTs, 961 participants) and hospital admission (RR 0.74; 95% CI 0.48 to 1.16; p=0.19; I2=70%; 3 RCTs, 8572 participants). CONCLUSIONS: The results of this meta-analysis do not support the use of colchicine as a treatment for reducing the risk of mortality or improving other relevant clinical outcomes in patients with COVID-19. However, RCTs investigating early treatment with colchicine (within 5 days of symptom onset or in patients with early-stage disease) are needed to fully elucidate the potential benefits of colchicine in this patient population. PROSPERO REGISTRATION NUMBER: CRD42022369850.

Molnupiravir for the treatment of COVID-19 outpatients: An updated meta-analysis.

BACKGROUND: The majority of available data on molnupiravir come from an unvaccinated COVID-19 population. Therefore, we conducted this meta-analysis to integrate evidence from recent randomized controlled trials (RCTs) as well as observational studies stratified by vaccination status to determine the clinical efficacy and safety of molnupiravir in COVID-19 outpatients. METHODS: We searched PubMed, Embase, the Cochrane Library, medRxiv, and ClinicalTrials.gov from inception to November 2023. We conducted our meta-analysis using RevMan 5.4 with risk ratio (RR) as the effect measure. RESULTS: We included 8 RCTs and 5 observational studies in our meta-analysis. Molnupiravir reduced the risk of all-cause mortality (RR 0.28; 95% CI: 0.20-0.79, I2 = 0%) but did not decrease the hospitalization rate (RR 0.67; 95% CI: 0.45-1.00, I2 = 53%) in the overall population; in the immunized population, no benefits were observed. Molnupiravir lowered the rate of no recovery (RR 0.78; 95% CI: 0.76-0.81, I2 = 0%) and increased virological clearance at day 5 (RR 2.68; 95% CI: 1.94-4.22, I2 = 85%). There was no increase in the incidence of adverse events. CONCLUSIONS: Molnupiravir does not decrease mortality and hospitalization rates in immunized patients with COVID-19. However, it does shorten the disease course and increases the recovery rate. The use of molnupiravir will need to be considered on a case-by-case basis in the context of the prevailing social circumstances, the resource setting, drug costs, and the healthcare burden.

Soluble guanylate cyclase stimulators for heart failure: a network meta-analysis and subgroup analyses of reduced and preserved ejection fraction.

BACKGROUND: Soluble guanylate cyclase (sGC) stimulators have been investigated for heart failure (HF) in several randomized controlled trials (RCTs). However, its place in the management guidelines of either HFrEF or HfpEF is still inconclusive. METHODS: We conducted a network meta-analysis synthesizing RCTs investigating sGC for HF management, which were retrieved by systematically searching five databases until January 24th, 2023. Dichotomous outcomes were pooled using risk ratio (RR) along with confidence interval (CI). RESULTS: Eight RCTs with a total of 7307 patients were included. Vericiguat 10 mg significantly reduced the composite cardiovascular (CVS) mortality and HF hospitalization in HF (RR: 0.88, 95% CI [0.79; 0.98]) and in HFrEF (RR: 0.87, 95% CI [0.78; 0.97]); however, it was not effective in HFpEF (RR: 0.69, 95% CI [0.15; 3.05]). Also, vericiguat 10 mg showed no difference compared to placebo regarding the incidence of all-cause mortality (RR: 0.96, 95% CI [0.84; 1.10]), any adverse events (AEs) (RR: 0.94, 95% CI [0.83; 1.07]), any serious AEs (RR: 0.91, 95% CI [0.81; 1.01]), and any AEs leading to drug discontinuation (RR: 1.14, 95% CI [0.92; 1.40]). CONCLUSION: Vericiguat 10 mg was effective in reducing the composite CVS mortality and HF hospitalization, with an acceptable safety profile. This was only observed in HFrEF patients, but not in HFpEF patients. However, our data regarding other agents (riociguat and praliciguat) and HFpEF can be underpowered, warranting further RCTs to clarify vericiguat 10 mg place in HFrEF management guidelines and to investigate sGC stimulators for HFpEF in large-scale trials.

Analysis of Conflicts of Interest in Studies Related to Robotics in Gastrointestinal and Abdominal Wall Surgery.

BACKGROUND: Industry payments to physicians represent a potential conflict of interest (COI) and can influence the study conclusions. This study aimed to evaluate the accuracy of the COIs reported in major surgical journals. STUDY DESIGN: Studies with at least one American author published between 2016 and 2021 that discussed observational and intervention studies assessing robotic surgery were included in the analysis. The Centers for Medicare & Medicaid Services' Open Payments database was used to collect the industry payments. A COI is defined as receiving funding from a robotics company while publishing research directly related to the company's products. A COI statement was defined as disclosed (or accurate) if the disclosure statement for the study in question acknowledged funding from the robotics companies. A COI was defined as undisclosed (or inaccurate) if the disclosure statement for the study in question did not acknowledge funding from the robotics companies. RESULTS: A total of 314 studies and 1978 authors were analyzed. Only 13.6% of the studies had accurate COI statements, whereas the majority (86.4%) had inaccurate COI disclosures. Additionally, 48.9% of the authors who received funding of $10,000 to $100,000 failed to report this amount in their disclosures, and 18% of the authors who received funding of $100,000 or more did not report it in their disclosures. CONCLUSIONS: There was a significant discordance between the self-reported COI in gastrointestinal and abdominal wall surgeries. This study calls for continued efforts to improve the definitions of what constitutes a relevant COI and encourages a standardized reporting process. It is imperative for investigators to make accurate disclosure statements.

Transjugular intrahepatic portosystemic shunt with or without variceal embolization to prevent variceal rebleeding: an updated meta-analysis.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is an established treatment for portal hypertension complications. Still, the role of adjuvant variceal embolization is a matter of debate. Thus, we aim to evaluate the efficacy and safety of TIPS with variceal embolization versus TIPS alone to prevent variceal rebleeding. RESEARCH DESIGN AND METHODS: We used PubMed, CENTRAL, and OVID to search for all randomized controlled trials (RCTs) and comparative observational studies up to 17 June 20221117 June 2022. We pooled binary outcomes using risk ratios (RRs) presented with 95% confidence intervals (CIs) using RevMan 5.4. RESULTS: We included 11 studies (two RCTs and nine observational studies) with 1024 patients. Pooled RR favored TIPS with embolization in preventing variceal rebleeding (RR 0.58, 95% CI: 0.44, 0.76); however, there was no difference between the two groups regarding shunt dysfunction (RR 0.92, 95% CI: 0.68, 1.23), encephalopathy (RR 0.88, 95% CI: 0.70, 1.11), and death (RR 0.97, 95% CI: 0.77, 1.22). CONCLUSIONS: TIPS with embolization can be an effective strategy for preventing variceal rebleeding; however, our results should be interpreted cautiously as most data were observational and the technical quality of the embolization is questionable. Further RCTs are required using the proper techniques of embolization and comparing TIPS with embolization with other treatment modalities such as endoscopic ligation, and balloon-occluded retrograde transvenous obliteration.

Benvitimod for the treatment of psoriasis: A systematic review and meta-analysis of randomized controlled trials.

Benvitimod is a topical drug that has recently been approved for mild to moderate psoriasis and atopic dermatitis. The drug has just completed phase 3 trials for psoriasis, which calls for a systematic update of current evidence on the efficacy and safety of this drug. We searched MEDLINE (PubMed), EMBASE, Science Direct, International Clinical Trials Registry Platform (ICTRP), Cochrane Central Register of Controlled Trials, and Google Scholar for all available randomized controlled trials concerning the topic. We included six randomized controlled trials evaluating the efficacy of benvitimod 1.0% with a total of 1925 patients. Our meta-analysis demonstrated that more patients in the benvitimod group achieved physician global assessment score of 0 or 1 (RR 6.53, 95% CI 4.39-9.71), psoriasis area and severity index (PASI) 75 (RR 4.34, 95% CI 2.96-6.36), PASI 90 (RR 8.83, 95% CI 5.22-14.95) and body surface area reduction (MD -3.85, 95% CI -4.83, -2.88) than placebo at week 12. Patient-reported outcomes were also analyzed, yielding a significant benefit in the benvitimod group for peak pruritus numerical rating scale (PP-NRS) score (MD -1.20, 95% CI -1.98, -0.42), ≥4-point decrease in PP-NRS score (RR 1.58, 95% CI, 1.24-2.03) and dermatology life quality index score (MD -2.54, 95% CI -4.00, -1.07). There was a significantly higher incidence of adverse events in the benvitimod group compared to placebo (RR 1.98, 95% CI 1.73-2.27), while the risk was found to be non-significant for serious adverse events. Benvitimod is an effective treatment of psoriasis as compared to a placebo. However, more large-scale, high-quality trials are needed to comment on the safety of this drug.