Effectiveness and safety of molnupiravir in the intended-use population: an observational cohort study.

OBJECTIVES: Previous research reported inconsistent results on the efficacy of molnupiravir in treating COVID-19. Moreover, efficacy was not assessed in the intended-use population (IUP), as defined by the FDA. Therefore, we aimed to evaluate the effectiveness and safety of molnupiravir for the treatment of COVID-19 in the IUP. METHODS: We performed a retrospective cohort study on all IUP in Israel's Clalit Health Services from January 16, 2022, to February 16, 2023. The effectiveness outcome was the incidence of hospitalization or death due to COVID-19, and the safety outcome was the incidence of all-cause mortality within 35 days of SARS-CoV-2 infection. Cox-proportional hazard models were used to analyse the data after 1:5 propensity-score matching. RESULTS: A total of 49 515 patients met the eligibility criteria. Of them, 3957 molnupiravir-treated patients were matched to 19 785 untreated patients. In molnupiravir-treated patients, 70 out of 3957 (5.1 per 10 000 person per day) experienced COVID-19-related hospitalization or death, compared with 699 out of 19 785 untreated patients (10.4 per 10 000 person per day); RR: 0.50 (95% CI, 0.39-0.64). All-cause mortality was also lower in the treated group, with 41 out of 3957 (3.0 per 10 000 person per day) experiencing mortality compared with 414 out of 19 785 untreated patients (6.1 per 10 000 person per day); RR: 0.50 (0.36-0.68). DISCUSSION: In a real-world cohort of IUP, molnupiravir therapy was associated with a significant reduction in hospitalizations or deaths due to COVID-19 and all-cause mortality.

Examining the Patterns of Mpox Vaccine Uptake in a Vulnerable Population.

BACKGROUND: The current Mpox outbreak presents unique vaccination challenges in vulnerable populations. Understanding factors associated with vaccine uptake in vulnerable populations is required for a successful vaccination campaign. METHODS: This population-based cohort study was conducted in Clalit Health Services and included all individuals eligible for the Modified Vaccinia Ankara vaccine. Cox proportional hazards models were used to assess the characteristics associated with uptake of the first vaccine dose. RESULTS: Attendance to a primary healthcare clinic in the Tel Aviv district, repeated sexually transmitted infection screening, and the recent purchase of HIV-PrEP or PDE5 inhibitors were associated with higher vaccine adherence, whereas previous nonadherence with recommended vaccines, low sociodemographic status, and history of HIV were associated with lower adherence. CONCLUSIONS: These findings highlight the need for proactive patient and healthcare provider-oriented educational campaigns to curb vaccine hesitancy, and may help direct resources toward underserved populations, hence increasing equality in vaccine enrollment.

Risk assessment of human mpox infections: retrospective cohort study.

OBJECTIVES: The global supply of vaccines against mpox (previously called monkeypox virus infection) was significantly lower than the demand. Therefore, evidence-based vaccine prioritization criteria, based on risk assessment were needed. Our objective was therefore to identify the characteristics of individuals at the highest risk for mpox. METHODS: This population-based cohort study included all Clalit Health Services (CHS) subjects assumed to be at risk for mpox. The eligibility criteria for inclusion were determined based on known characteristics of people with infection worldwide and insights of lesbian, gay, bisexual, transgender, queer+ (LGBTQ+) -specialized CHS clinicians. Cox hazards models were used to identify the risk factors for mpox within the study cohort. The study commenced on 6 June 2022, the date of the first known mpox in CHS members, until 31 July 2022, when the mpox vaccination campaign started. RESULTS: A total of 8088 individuals of 4.7 million CHS members (0.18%) were identified according to the study inclusion criteria. Of those, 69 (0.85%) developed infection during the study period. Risk factors for mpox were birth in 1980 or later (hazard ratio, 5.04; 95% CI, 2.11-12.02), history of syphilis (2.62; 1.58-4.35), registration to primary healthcare clinics in the Tel Aviv district (2.82; 1.44-5.54), HIV-pre-exposure prophylaxis medication use (3.96; 2.14-7.31), PDE5 inhibitors use (2.92; 1.77-4.84), and recent sexually transmitted infections (STIs) within the last 18 months (2.27; 1.35-3.82). No infections were observed in individuals with none of the factors. Individuals with three or more risk factors had a 20.30-fold (10.39-39.69) higher risk for mpox compared with those with 0-2, with 85.5% (75.0-92.8%) sensitivity and 77.8% (76.9-78.7%) specificity. DISCUSSION: Weighting individuals' risk levels based on validated risk factors against vaccine availability can assist health systems in the equitable prioritization of vaccine allocation in various future outbreaks, given supply-demand gaps.

Real-world effectiveness of a single dose of mpox vaccine in males.

The recent global outbreak of the monkeypox (mpox) virus in humans was declared a public health emergency by the World Health Organization in July 2022. The smallpox and mpox vaccine (JYNNEOS; Modified Vaccinia Ankara-Bavarian Nordic; MVA-BN), provided as a two-dose regimen, is currently the primary vaccine utilized against mpox. However, the efficacy of MVA-BN against mpox has never been demonstrated in clinical trials to date. Due to the limited supply of vaccines, the World Health Organization has recommended prioritizing the vaccination of high-risk groups. We evaluated the real-world effectiveness of a single, subcutaneous dose of MVA-BN in this observational, retrospective cohort study, which included the analysis of electronic health records of all members of Clalit Health Services eligible for the vaccine on 31 July 2022. We used a Cox proportional hazards regression model with time-dependent covariates to estimate the association between vaccination and mpox while adjusting for sociodemographic and clinical risk factors. In an analysis of 2,054 male individuals who met vaccine eligibility criteria, 1,037 (50%) were vaccinated during the study recruitment period and completed at least 90 d of follow-up. During the study period, 5 and 16 infections were confirmed in vaccinated and unvaccinated individuals, respectively. The adjusted vaccine effectiveness was estimated at 86% (95% confidence interval, 59-95%). Our results suggest that a single dose of subcutaneous MVA-BN in this high-risk cohort is associated with a significantly lower risk of MPXV infection.

Party keepers: a significant community-based intervention for harm reduction.

BACKGROUND: Gay men use recreational drugs more often than heterosexuals-especially at social events. While partying at a venue, partygoers are at risk of drug overdosing, without access to an emergency help. This study evaluates a unique and novel intervention aimed at training men who have sex with men (MSM) and transgender individuals who frequent parties, to provide immediate assistance on-site to partygoers who have overdosed. METHODS: The Party Keepers (PK) course is a unique 4-h training course that provides the participants with tools to identify, prevent, and treat common medical syndromes that are associated with excessive substance use. Participants were asked to complete a questionnaire on their sociodemographic attributes; their sexual risk behaviour; pre-exposure prophylaxis (PrEP) use and drug-use behaviour before and after the course; and the emergency situations they encountered in party venues after the course. RESULTS: Of the 85 participants who completed the training and left valid contact information, 52 (62%) completed the questionnaires. Their average age was 37.0 years, most lived in Tel-Aviv, and were single. Participants reported that, after the course, they reduced their own use of recreational drugs (cocaine, amyl nitrates, alcohol), reduced their sexual risk behaviours, and significantly increased their use of PrEP. Of all the PKs, 63% (N = 32) indicated that they now provided first-aid and other assistance to partygoers at public venues, which enhanced their sense of community responsibility. In the multivariate analysis, a high level of confidence as a PK, and the knowledge gained in the course, predicted the incidence of subsequent assistance to partygoers in emergency situations. CONCLUSIONS: The PK initiative-a harm-reduction intervention led by peers, aimed at fighting drug overdosing at gay venues-was useful in reducing drug use and sexual risk behaviours among the course participants. Most course participants also responded to drug-related emergency situations at gay parties, as a result. This evaluation of community health intervention within a sexual minority community can help health policy makers design more community based interventions and allocate resources to include community participants in harm-reduction policies.

The impact of COVID-19 lockdown on men having sex with men (MSM).

Social distancing including lockdowns are acceptable measures to cope with the COVID-19 pandemic. In this cross sectional study, we surveyed the impact of these measurements on sexual behavior and pre-exposure prophylaxis for HIV (PrEP) use among MSM. A digital questionnaire was distributed via social media and geographically based meeting applications after the first lockdown (March-April 2020). 1194 MSM responded, 91.8% were HIV negative, 19.4% of them used PrEP regularly, and 8.2% were people living with HIV (PLWH). Median age was 34.5 years. 54.4% reported that they kept strictly social distancing guidelines. Low education, hazardous sexual behavior, moderate/severe, and depression predicted low compliance with social distancing guidelines. 66.7% reported a significant decrease in the number of casual sex partners. 55% of those who took PrEP reduced their PrEP intake. Many of the PLWH and PrEP users reduced their medical follow-up. In light of the continuous outbreak and the risk of further outbreaks in the future consideration should be given to provide continuing access to HIV and sexual health clinics.

Triple site sexually transmitted infection testing as a crucial component of surveillance for men who have sex with men: A prospective cohort study.

Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections are common among men who have sex with men (MSM). Many oropharyngeal and anorectal infections remain asymptomatic. We aimed to evaluate triple-site screening following PrEP introduction. We enrolled a prospective cohort study including 210 asymptomatic MSM during 2019-2020, analyzed by groups: HIV positive (HIV+), HIV-uninfected using PrEP (HIV-/PrEP+), or HIV-uninfected not using PrEP (HIV-/PrEP-). A self-administered questionnaire captured demographic information and sexual risk-taking behaviors. CT/NG testing results were compared between study groups and predictors of infection were evaluated. We included 59 HIV+, 70 HIV-/PrEP+, and 81 HIV-/PrEP- subjects. 30% (n = 62) of participants tested positive for CT/NG. HIV-/PrEP+ group had highest proportion of infections (n = 33, 47%) followed by HIV-/PrEP- (n = 16, 22%) and HIV+ (n=13, 20%; p < .001). Importantly, 98% (80/82) of pharyngeal/anorectal CT/NG infections were missed in genitourinary tract screening alone. PrEP use and previous syphilis infection were the strongest risk factor for CT/NG. Extra-genital asymptomatic CT/NG infections were prevalent among MSM. These data highlight the importance of routine extra-genital CT/NG testing in asymptomatic sexually active MSM. The study describes the consequences for three-site testing lack of implementation in the PrEP era.

Minimizing Venous Thromboembolism in Feminizing Hormone Therapy: Applying Lessons From Cisgender Women and Previous Data.

OBJECTIVE: To review he impact of estrogen-containing feminizing hormone regimens on transgender individuals' risk for VTE. METHODS: We evaluated VTE risk by screening 1170 relevant studies published from 1994 to 2020, focusing on meta-analysis data. RESULTS: The type of oral estrogen, route of administration, patient demographics, and comorbidities may affect the risk of VTE. Venous thrombosis is the most common vascular complication associated with HT. CONCLUSION: Conjugated equine estrogens and 17-ß estradiol appear to be safer than oral ethinyl estradiol. Transdermal estrogen formulations appear to be the least thrombogenic estrogens. Estrogens used concomitantly with progestins increase the risk of VTE compared to estrogens alone. To date, there are no data to demonstrate the benefit of holding HT prior to vaginoplasty or other gender affirming surgeries. For most young, healthy transgender women, there is little risk of VTE with HT, while older patients with risk factors should be discussed case by case.