METHODS: We systematically searched PubMed, Cochrane Central Register of Controlled Trials, Google Scholar, and medRxiv (preprint repository) databases (up to 7 January 2021). Pooled effect sizes with 95% confidence interval (CI) were generated using random-effects and inverse variance heterogeneity models. The risk of bias of the included RCTs was appraised using version 2 of the Cochrane risk-of-bias tool for randomized trials.
RESULTS: Six RCTs were included: two trials with an overall low risk of bias and four trials had some concerns regarding the overall risk of bias. Our meta-analysis did not find significant mortality benefits with the use of tocilizumab among patients with COVID-19 relative to non-use of tocilizumab (pooled hazard ratio = 0.83; 95% CI 0.66-1.05, n = 2,057). Interestingly, the estimated effect of tocilizumab on the composite endpoint of requirement for mechanical ventilation and/or all-cause mortality indicated clinical benefits, with some evidence against our model hypothesis of no significant effect at the current sample size (pooled hazard ratio = 0.62; 95% CI 0.42-0.91, n = 749).
CONCLUSION: Despite no clear mortality benefits in hospitalized patients with COVID-19, tocilizumab appears to reduce the likelihood of progression to mechanical ventilation.
METHODS: This prospective open-label single-arm observational clinical trial enrolled 41 patients who underwent liver transplantation between 2010 and 2016 because of a condition related to chronic HBV infection. At the time of enrollment, all patients had taken entecavir and discontinued HBIG administration. When hepatitis B surface antibody titer was undetectable after the withdrawal of HBIG, a recombinant HBV vaccine was injected intramuscularly at month 0, 1, and 6.
RESULTS: After excluding 5 patients who dropped out and 2 patients who had a persistent hepatitis B surface antibody titer, 9 (26.5%) of 34 patients had a positive vaccination response. The median hepatitis B surface antibody titer at seroconversion was 86 (12-1000) IU/L, and those at the end of follow-up were 216 (30-1000) IU/L. No patients experienced HBV recurrence during the study period. Sex (female, odds ratio 32.91 [1.83-592.54], P = .018) and the dosing interval of HBIG before withdrawal (≥90 days, 16.21 [1.21-217.31], P = .035) were independent contributing factors for positive response to the vaccination.
CONCLUSION: HBV vaccination still deserves consideration as active immunoprophylaxis after liver transplantation because it could provide added immunity to nucleoside/nucleotide analogs monotherapy with excellent cost-effectiveness.
METHODS: A systematic literature search with no language restriction was performed in electronic databases and preprint repositories to identify eligible studies published up to 29 June 2021. The outcomes of interest were hospital admission and all-cause mortality. A random-effects model was used to estimate the pooled odds ratio (OR) for outcomes of interest with the use of neutralizing monoclonal antibodies relative to nonuse of neutralizing monoclonal antibodies, at 95% confidence intervals (CI).
RESULTS: Our systematic literature search identified nine randomized controlled trials. Three trials had an overall low risk of bias, while four trials had some concerns in the overall risk of bias. The meta-analysis revealed no statistically significant difference in the odds of mortality (pooled OR = 0.69; 95% CI 0.33-1.47), but a statistically significant reduction in the odds of hospital admission (pooled OR = 0.29; 95% CI 0.21-0.42), with the administration of a neutralizing monoclonal antibody among patients with COVID-19, relative to non-administration of a neutralizing monoclonal antibody, at the current sample size.
CONCLUSION: The reduced risk of hospital admission with neutralizing monoclonal antibodies use suggests that the timing of neutralizing antibodies administration is key in preventing hospital admission and, ultimately, death. Future randomized trials should aim to determine if the clinical outcomes with neutralizing monoclonal antibodies differ based on serostatus.
METHODS: This study aimed to conduct a 5-year budget impact analysis of the proposed stratified treatment cascade for HCV treatment in Malaysia. A disease progression model that was developed based on model-predicted HCV epidemiology data was used for the analysis, where all HCV patients in scenario A were treated with SOF/DAC for all disease stages while in scenario B, SOF/DAC was used only for non-cirrhotic patients and SOF/VEL was used for the cirrhotic patients. Healthcare costs associated with DAA therapy and disease stage monitoring were included to estimate the downstream cost implications.
RESULTS: The stratified treatment cascade with 109 in Scenario B was found to be cost-saving compared to Scenario A. The cumulative savings for the stratified treatment cascade was USD 1.4 million over 5 years.
DISCUSSION: A stratified treatment cascade with SOF/VEL was expected to be cost-saving and can result in a budget impact reduction in overall healthcare expenditure in Malaysia.
METHODS: A pilot study was conducted in four primary healthcare (PHC) centers in Malaysia. The model's key features included on-site HCV ribonucleic acid (RNA) testing using a shared GeneXpert® system; noninvasive biomarkers for cirrhosis diagnosis; and extended care to PWID referred from nearby PHC centers and outreach programs. The feasibility assessment focused on three aspects of the model: demand (i.e., uptake of HCV RNA testing and treatment), implementation (i.e., achievement of each step in the HCV care cascade), and practicality (i.e., ability to identify PWID with HCV and expedite treatment initiation despite resource constraints).
RESULTS: A total of 199 anti-HCV-positive PWID were recruited. They demonstrated high demand for HCV care, with a 100% uptake of HCV RNA testing and 97.4% uptake of direct-acting antiviral treatment. The rates of HCV RNA positivity (78.4%) and sustained virologic response (92.2%) were comparable to standard practice, indicating the successful implementation of the model. The model was also practical, as it covered non-opioid-substitution-therapy-receiving individuals and enabled same-day treatment in 71.1% of the participants.
CONCLUSIONS: The modified same-day test-and-treat model is feasible in improving HCV care for rural PWID. The study finding suggests its potential for wider adoption in HCV care for hard-to-reach populations.
SOURCES OF DATA: Recent published literature.
AREAS OF AGREEMENT: Corticosteroids and immunomodulators that antagonize the interleukin-6 (IL-6) receptor have been shown to play a critical role in modulating inflammation and improving clinical outcomes in hospitalized patients. Inhaled budesonide reduces the time to recovery in older patients with mild-to-moderate COVID-19 managed in the community.
AREAS OF CONTROVERSY: The clinical benefit of remdesivir remains controversial with conflicting evidence from different trials. Remdesivir led to a reduction in time to clinical recovery in the ACTT-1 trial. However, the World Health Organization SOLIDARITY and DISCOVERY trial did not find a significant benefit on 28-day mortality and clinical recovery.
GROWING POINTS: Other treatments currently being investigated include antidiabetic drug empagliflozin, antimalarial drug artesunate, tyrosine kinase inhibitor imatinib, immunomodulatory drug infliximab, antiviral drug favipiravir, antiparasitic drug ivermectin and antidepressant drug fluvoxamine.
AREAS TIMELY FOR DEVELOPING RESEARCH: The timing of therapeutic interventions based on postulated mechanisms of action and the selection of clinically meaningful primary end points remain important considerations in the design and implementation of COVID-19 therapeutic trials.
METHODS: Using empirical data from Hartford, Connecticut, we deployed a stochastic block model to simulate an injection network of 1574 PWID. We used a susceptible-infected model for HCV and human immunodeficiency virus to evaluate the effectiveness of several HCV TasP strategies, including in combination with OAT and SSP scale-up, over 20 years.
RESULTS: At the highest HCV prevalence (75%), when OAT coverage is increased from 10% to 40%, combined with HCV treatment of 10% per year and SSP scale up to 40%, the time to achieve microelimination is reduced from 18.4 to 11.6 years. At the current HCV prevalence (60%), HCV TasP strategies as low as 10% coverage per year may achieve HCV microelimination within 10 years, with minimal impact from additional OAT scale-up. Strategies based on mass initial HCV treatment (50 per 100 PWID the first year followed by 5 per 100 PWID thereafter) were most effective in settings with HCV prevalence of 60% or lower.
CONCLUSIONS: Scale-up of HCV TasP is the most effective strategy for microelimination of HCV. OAT scale-up, however, scale-up may be synergistic toward achieving microelimination goals when HCV prevalence exceeds 60% and when HCV treatment coverage is 10 per 100 PWID per year or lower.