Risk of Arterial and Venous Thrombotic Events Among Patients with COVID-19: A Multi-National Collaboration of Regulatory Agencies from Canada, Europe, and United States.

Purpose: Few studies have examined how the absolute risk of thromboembolism with COVID-19 has evolved over time across different countries. Researchers from the European Medicines Agency, Health Canada, and the United States (US) Food and Drug Administration established a collaboration to evaluate the absolute risk of arterial (ATE) and venous thromboembolism (VTE) in the 90 days after diagnosis of COVID-19 in the ambulatory (eg, outpatient, emergency department, nursing facility) setting from seven countries across North America (Canada, US) and Europe (England, Germany, Italy, Netherlands, and Spain) within periods before and during COVID-19 vaccine availability. Patients and Methods: We conducted cohort studies of patients initially diagnosed with COVID-19 in the ambulatory setting from the seven specified countries. Patients were followed for 90 days after COVID-19 diagnosis. The primary outcomes were ATE and VTE over 90 days from diagnosis date. We measured country-level estimates of 90-day absolute risk (with 95% confidence intervals) of ATE and VTE. Results: The seven cohorts included 1,061,565 patients initially diagnosed with COVID-19 in the ambulatory setting before COVID-19 vaccines were available (through November 2020). The 90-day absolute risk of ATE during this period ranged from 0.11% (0.09-0.13%) in Canada to 1.01% (0.97-1.05%) in the US, and the 90-day absolute risk of VTE ranged from 0.23% (0.21-0.26%) in Canada to 0.84% (0.80-0.89%) in England. The seven cohorts included 3,544,062 patients with COVID-19 during vaccine availability (beginning December 2020). The 90-day absolute risk of ATE during this period ranged from 0.06% (0.06-0.07%) in England to 1.04% (1.01-1.06%) in the US, and the 90-day absolute risk of VTE ranged from 0.25% (0.24-0.26%) in England to 1.02% (0.99-1.04%) in the US. Conclusion: There was heterogeneity by country in 90-day absolute risk of ATE and VTE after ambulatory COVID-19 diagnosis both before and during COVID-19 vaccine availability.

Epigenome-wide association study of biomarkers of liver function identifies albumin-associated DNA methylation sites among male veterans with HIV.

Background: Liver disease (LD) is an important cause of morbidity and mortality for people with HIV (PWH). The molecular factors linked with LD in PWH are varied and incompletely characterized. We performed an epigenome-wide association study (EWAS) to identify associations between DNA methylation (DNAm) and biomarkers of liver function-aspartate transaminase, alanine transaminase, albumin, total bilirubin, platelet count, FIB-4 score, and APRI score-in male United States veterans with HIV. Methods: Blood samples and clinical data were obtained from 960 HIV-infected male PWH from the Veterans Aging Cohort Study. DNAm was assessed using the Illumina 450K or the EPIC 850K array in two mutually exclusive subsets. We performed a meta-analysis for each DNAm site measured by either platform. We also examined the associations between four measures of DNAm age acceleration (AA) and liver biomarkers. Results: Nine DNAm sites were positively associated with serum albumin in the meta-analysis of the EPIC and 450K EWAS after correcting for multiple testing. Four DNAm sites (cg16936953, cg18942579, cg01409343, and cg12054453), annotated within the TMEM49 and four of the remaining five sites (cg18181703, cg03546163, cg20995564, and cg23966214) annotated to SOCS3, FKBP5, ZEB2, and SAMD14 genes, respectively. The DNAm site, cg12992827, was not annotated to any known coding sequence. No significant associations were detected for the other six liver biomarkers. Higher PhenoAA was significantly associated with lower level of serum albumin (ß = -0.007, p-value = 8.6 × 10-4, CI: -0.011116, -0.002884). Conclusion: We identified epigenetic associations of both individual DNAm sites and DNAm AA with liver function through serum albumin in men with HIV. Further replication analyses in independent cohorts are warranted to confirm the epigenetic mechanisms underlying liver function and LD in PWH.

Cost and cost-effectiveness of a real-world HCV treatment program among HIV-infected individuals in Myanmar.

INTRODUCTION: Over half of those hepatitis C virus (HCV)/HIV coinfected live in low-income and middle-income countries, and many remain undiagnosed or untreated. In 2016, Médecins Sans Frontières (MSF) established a direct-acting antiviral (DAA) treatment programme for people HCV/HIV coinfected in Myanmar. The purpose of our study was to evaluate the real-world cost and cost-effectiveness of this programme, and potential cost-effectiveness if implemented by the Ministry of Health (MoH). METHODS: Costs (patient-level microcosting) and treatment outcomes were collected from the MSF prospective cohort study in Dawei, Myanmar. A Markov model was used to assess cost-effectiveness of the programme compared with no HCV treatment from a health provider perspective. Estimated lifetime and healthcare costs (in 2017 US$) and health outcomes (in disability-adjusted life-years (DALYs)) were simulated to calculate the incremental cost-effectiveness ratio (ICER), compared with a willingness-to-pay threshold of per capita Gross Domestic Product in Myanmar ($1250). We evaluated cost-effectiveness with updated quality-assured generic DAA prices and potential cost-effectiveness of a proposed simplified treatment protocol with updated DAA prices if implemented by the MoH. RESULTS: From November 2016 to October 2017, 122 with HIV/HCV-coinfected patients were treated with DAAs (46% with cirrhosis), 96% (n=117) achieved sustained virological response. Mean treatment costs were $1229 (without cirrhosis) and $1971 (with cirrhosis), with DAA drugs being the largest contributor to cost. Compared with no treatment, the program was cost-effective (ICER $634/DALY averted); more so with updated prices for quality-assured generic DAAs (ICER $488/DALY averted). A simplified treatment protocol delivered by the MoH could be cost-effective if associated with similar outcomes (ICER $316/DALY averted). CONCLUSIONS: Using MSF programme data, the DAA treatment programme for HCV among HIV-coinfected individuals is cost-effective in Myanmar, and even more so with updated DAA prices. A simplified treatment protocol could enhance cost-effectiveness if further rollout demonstrates it is not associated with worse treatment outcomes.

Trends in Treatment Uptake and Provider Specialty for Hepatitis C Virus (HCV) Infection in the Veterans Affairs Healthcare System: Results From the Electronically Retrieved Cohort of HCV-Infected Veterans (ERCHIVES).

Between 2001 and 2017, 108133 persons (45.7% of diagnosed cases) were initiated on anti-hepatitis C virus treatment in the Veterans Affairs healthcare system. In 2017, nonphysician clinicians accounted for 22.2% of prescriptions, infectious diseases specialists for 14.9%, and gastroenterologists/hepatologists for 10.3%. In the pre-direct-acting antiviral era, they accounted for 7.2%, 26.7%, and 11.6%, respectively.