Early Treatment with Pegylated Interferon Lambda for Covid-19.

BACKGROUND: The efficacy of a single dose of pegylated interferon lambda in preventing clinical events among outpatients with acute symptomatic coronavirus disease 2019 (Covid-19) is unclear. METHODS: We conducted a randomized, controlled, adaptive platform trial involving predominantly vaccinated adults with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Brazil and Canada. Outpatients who presented with an acute clinical condition consistent with Covid-19 within 7 days after the onset of symptoms received either pegylated interferon lambda (single subcutaneous injection, 180 µg) or placebo (single injection or oral). The primary composite outcome was hospitalization (or transfer to a tertiary hospital) or an emergency department visit (observation for >6 hours) due to Covid-19 within 28 days after randomization. RESULTS: A total of 933 patients were assigned to receive pegylated interferon lambda (2 were subsequently excluded owing to protocol deviations) and 1018 were assigned to receive placebo. Overall, 83% of the patients had been vaccinated, and during the trial, multiple SARS-CoV-2 variants had emerged. A total of 25 of 931 patients (2.7%) in the interferon group had a primary-outcome event, as compared with 57 of 1018 (5.6%) in the placebo group, a difference of 51% (relative risk, 0.49; 95% Bayesian credible interval, 0.30 to 0.76; posterior probability of superiority to placebo, >99.9%). Results were generally consistent in analyses of secondary outcomes, including time to hospitalization for Covid-19 (hazard ratio, 0.57; 95% Bayesian credible interval, 0.33 to 0.95) and Covid-19-related hospitalization or death (hazard ratio, 0.59; 95% Bayesian credible interval, 0.35 to 0.97). The effects were consistent across dominant variants and independent of vaccination status. Among patients with a high viral load at baseline, those who received pegylated interferon lambda had lower viral loads by day 7 than those who received placebo. The incidence of adverse events was similar in the two groups. CONCLUSIONS: Among predominantly vaccinated outpatients with Covid-19, the incidence of hospitalization or an emergency department visit (observation for >6 hours) was significantly lower among those who received a single dose of pegylated interferon lambda than among those who received placebo. (Funded by FastGrants and others; TOGETHER ClinicalTrials.gov number, NCT04727424.).

Effect of Early Treatment with Ivermectin among Patients with Covid-19.

BACKGROUND: The efficacy of ivermectin in preventing hospitalization or extended observation in an emergency setting among outpatients with acutely symptomatic coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is unclear. METHODS: We conducted a double-blind, randomized, placebo-controlled, adaptive platform trial involving symptomatic SARS-CoV-2-positive adults recruited from 12 public health clinics in Brazil. Patients who had had symptoms of Covid-19 for up to 7 days and had at least one risk factor for disease progression were randomly assigned to receive ivermectin (400 µg per kilogram of body weight) once daily for 3 days or placebo. (The trial also involved other interventions that are not reported here.) The primary composite outcome was hospitalization due to Covid-19 within 28 days after randomization or an emergency department visit due to clinical worsening of Covid-19 (defined as the participant remaining under observation for >6 hours) within 28 days after randomization. RESULTS: A total of 3515 patients were randomly assigned to receive ivermectin (679 patients), placebo (679), or another intervention (2157). Overall, 100 patients (14.7%) in the ivermectin group had a primary-outcome event, as compared with 111 (16.3%) in the placebo group (relative risk, 0.90; 95% Bayesian credible interval, 0.70 to 1.16). Of the 211 primary-outcome events, 171 (81.0%) were hospital admissions. Findings were similar to the primary analysis in a modified intention-to-treat analysis that included only patients who received at least one dose of ivermectin or placebo (relative risk, 0.89; 95% Bayesian credible interval, 0.69 to 1.15) and in a per-protocol analysis that included only patients who reported 100% adherence to the assigned regimen (relative risk, 0.94; 95% Bayesian credible interval, 0.67 to 1.35). There were no significant effects of ivermectin use on secondary outcomes or adverse events. CONCLUSIONS: Treatment with ivermectin did not result in a lower incidence of medical admission to a hospital due to progression of Covid-19 or of prolonged emergency department observation among outpatients with an early diagnosis of Covid-19. (Funded by FastGrants and the Rainwater Charitable Foundation; TOGETHER ClinicalTrials.gov number, NCT04727424.).

Oral Fluvoxamine With Inhaled Budesonide for Treatment of Early-Onset COVID-19 : A Randomized Platform Trial.

BACKGROUND: Previous trials have demonstrated the effects of fluvoxamine alone and inhaled budesonide alone for prevention of disease progression among outpatients with COVID-19. OBJECTIVE: To determine whether the combination of fluvoxamine and inhaled budesonide would increase treatment effects in a highly vaccinated population. DESIGN: Randomized, placebo-controlled, adaptive platform trial. (ClinicalTrials.gov: NCT04727424). SETTING: 12 clinical sites in Brazil. PARTICIPANTS: Symptomatic adults with confirmed SARS-CoV-2 infection and a known risk factor for progression to severe disease. INTERVENTION: Patients were randomly assigned to either fluvoxamine (100 mg twice daily for 10 days) plus inhaled budesonide (800 mcg twice daily for 10 days) or matching placebos. MEASUREMENTS: The primary outcome was a composite of emergency setting retention for COVID-19 for more than 6 hours, hospitalization, and/or suspected complications due to clinical progression of COVID-19 within 28 days of randomization. Secondary outcomes included health care attendance (defined as hospitalization for any cause or emergency department visit lasting >6 hours), time to hospitalization, mortality, patient-reported outcomes, and adverse drug reactions. RESULTS: Randomization occurred from 15 January to 6 July 2022. A total of 738 participants were allocated to oral fluvoxamine plus inhaled budesonide, and 738 received placebo. The proportion of patients observed in an emergency setting for COVID-19 for more than 6 hours or hospitalized due to COVID-19 was lower in the treatment group than the placebo group (1.8% [95% credible interval {CrI}, 1.1% to 3.0%] vs. 3.7% [95% CrI, 2.5% to 5.3%]; relative risk, 0.50 [95% CrI, 0.25 to 0.92]), with a probability of superiority of 98.7%. No relative effects were found between groups for any of the secondary outcomes. More adverse events occurred in the intervention group than the placebo group, but no important differences between the groups were detected. LIMITATION: Low event rate overall, consistent with contemporary trials in vaccinated populations. CONCLUSION: Treatment with oral fluvoxamine plus inhaled budesonide among high-risk outpatients with early COVID-19 reduced the incidence of severe disease requiring advanced care. PRIMARY FUNDING SOURCE: Latona Foundation, FastGrants, and Rainwater Charitable Foundation.

Towards elimination of mother-to-child transmission of HIV in Rwanda: a nested case-control study of risk factors for transmission.

BACKGROUND: Mother-to-child HIV transmission (MTCT) has substantially declined since the scale-up of prevention programs around the world, including Rwanda. To achieve full elimination of MTCT, it is important to understand the risk factors associated with residual HIV transmission, defined as MTCT at the population-level that still occurs despite universal access to PMTCT. METHODS: We performed a case control study of children born from mothers with HIV with known vital status at 18 months from birth, who were followed in three national cohorts between October and December 2013, 2014, and 2015 in Rwanda. Children with HIV were matched in a ratio of 1:2 with HIV-uninfected children and a conditional logistic regression model was used to investigate risk factors for MTCT. RESULTS: In total, 84 children with HIV were identified and matched with 164 non-infected children. The median age of mothers from both groups was 29 years (interquartile range (IQR): 24-33). Of these mothers, 126 (51.4 %) initiated antiretroviral therapy (ART) before their pregnancy on record. In a multivariable regression analysis, initiation of ART in the third trimester (Adjusted Odds Ratio [aOR]: 9.25; 95 % Confidence Interval [95 % CI]: 2.12-40.38) and during labour or post-partum (aOR: 8.87; 95 % CI: 1.92-40.88), compared to initiation of ART before pregnancy, increased the risk of MTCT. Similarly, offspring of single mothers (aOR: 7.15; 95 % CI: 1.15-44.21), and absence of postpartum neonatal ART prophylaxis (aOR: 7.26; 95 % CI: 1.66-31.59) were factors significantly associated with MTCT. CONCLUSIONS: Late ART initiation for PMTCT and lack of postpartum infant prophylaxis are still the most important risk factors to explain MTCT in the era of universal access. Improved early attendance at antenatal care, early ART initiation, and enhancing the continuum of care especially for single mothers is crucial for MTCT elimination in Rwanda.

Substance Use as a Mechanism for Social Inclusion among Gay, Bisexual, and Other Men Who Have Sex with Men in Vancouver, Canada.

Background: Previous research demonstrates that substance use preferences and social-sexual environments are highly interrelated for gay, bisexual, and other men who have sex with men (gbMSM). Objective: We conducted a qualitative study to explore the socio-cultural context of substance use among local gbMSM communities in Metro Vancouver, Canada. Methods: Twenty gbMSM were purposively sampled from the larger Momentum Health Study cohort, a sexual health study of gbMSM in Greater Vancouver. Participants were demographically diverse in terms of HIV serostatus, age, income, ethnicity, and area of residence within the city and neighboring suburbs. Community maps generated by participants during formative research served as prompts for semi-structured interviews which were audio recorded and transcribed verbatim. Thematic analysis identified three themes of common experience. Results: First, participants indicated that substance use is intrinsically social in Vancouver gbMSM communities and that it functions as both a means of social inclusion and exclusion. Second, a distinction was made between types of substances and the location and context of their use, with specific substances having particular uses and meanings. Third, analysis suggested that gbMSM change their substance use over the life course and that this is affected by shifting priorities as people age. Discussion: For Vancouver gbMSM communities, substance use serves several social-cultural functions and can simultaneously serve as both a potential facilitator and barrier for community connection. Future research and health programing should consider venue and context specific messaging and recognize the heterogeneity of substance use within the larger gbMSM population.

The role of community health workers and local leaders in reducing attrition among participant in the AIDS indicator survey and HIV incidence in a national cohort study in Rwanda.

BACKGROUND: Retention of participants in longitudinal prospective surveys can challenging for population health researchers. Community health workers (CHWs) may help reduce attrition. METHODS: We used data came from a longitudinal prospective household-based survey targeting women and men in Rwanda, collected between June 2013 and December 2014. The sample was drawn from a population that included all residents of all 30 districts, 416 sectors, and 14,837 villages in Rwanda. The outcome measure was time to loss-to-follow-up. Follow up visits occurred at three, six and nine, and 12 months. A Cox proportional hazards model was constructed to identify factors independently associated with time to loss-to-follow-up. RESULTS: Overall, 14,222 respondents consented to be interviewed at baseline. At the end of 12 months of follow up, 13,728 were revisited and consented to participate at 12 months of follow up. The overall attrition rate was 8.0%. A majority of those lost (54.3%) were less than 25 years of age, male (55.1%), not living in union (67.3%), had no education level or had primary education level (71.4%), or were in the highest wealth index (54.2%). Compared to illiterate, secondary education was negatively associated with attrition. CONCLUSION: The Rwanda AIDS indicator and HIV incidence survey recorded a very high retention of participants after 12 months. CHWs and local leaders played a major role to reduce attrition rate and identifying factors associated with loss-to-follow-up can help CHWs strengthen the quality of longitudinal survey data.

Association Between Internet Use and Body Dissatisfaction Among Young Females: Cross-Sectional Analysis of the Canadian Community Health Survey.

BACKGROUND: Recent research suggests Internet exposure, including Facebook use, is positively correlated with body dissatisfaction, especially among girls and young women. Canada has one of the highest Internet access rates in the world, yet no previous study has examined this relationship using nationally representative data. OBJECTIVE: Our objective was to evaluate the relationship between Internet use and body dissatisfaction among a national, population-based sample of Canadian females 12-29 years of age. METHODS: We used cross-sectional data from the Canadian Community Health Survey 2011-2012. Body dissatisfaction was measured using a 5-point Likert scale and defined as "very dissatisfied/dissatisfied" with one's body. The explanatory variable was time spent using the Internet per week in the past 3 months, ranging from none/<1 hour to >20 hours. We used multinomial logistic regression to investigate whether greater Internet use was associated with increasing odds of being very dissatisfied/dissatisfied, neutral, or satisfied with one's body, using very satisfied as the referent. Probability survey sampling weights were applied to all analyses. RESULTS: Of 2983 included participants, sampled to represent 940,786 young Canadian females, most were 20-29 years old (61.98%) and living in households with an annual income Can $80,000 or more (44.61%). The prevalence of body dissatisfaction was 14.70%, and 25- to 29-year-olds were more likely than 12- to 14-year-olds to be very dissatisfied or dissatisfied with their body (20.76% vs 6.34%). Few (5.01%) reported none/<1 hour of Internet use, over half (56.93%) reported 1-10 hours, and one-fifth (19.52%) reported spending >20 hours online per week. Adjusting for age and income, the odds of being very dissatisfied/dissatisfied, relative to very satisfied, were greater in the highest versus lowest Internet use group (adjusted odds ratio [AOR] 3.03, 95% CI 1.19-7.70). The AORs for this level of body dissatisfaction increased across increasing levels of Internet use, ranging from 0.88 (95% CI 0.35-2.21) to 3.03 (95% CI 1.19-7.70). Additionally, those who spent 11-14 hours online were more likely to be neutral (AOR 3.66, 95% CI 1.17-11.45) and those who spent 15-20 hours online were more likely to be neutral (AOR 4.36, 95% CI 1.18-16.13) or satisfied (AOR 2.82, 95% CI 1.14-7.01) with their bodies, relative to very satisfied, compared with those spending no time or <1 hour online. CONCLUSIONS: A substantial proportion of Canadian females 12-29 years of age spent large amounts of time (>20 hours) on the Internet each week, and body dissatisfaction was significantly more likely among this group. Those who spent 11-20 hours online were also more likely to be less satisfied with their bodies. Efforts are needed to support girls and young women to achieve and maintain a positive body image in today's digital age.

Drug resistance mutations after the first 12 months on antiretroviral therapy and determinants of virological failure in Rwanda.

OBJECTIVE: To evaluate HIV drug resistance (HIVDR) and determinants of virological failure in a large cohort of patients receiving first-line tenofovir-based antiretroviral therapy (ART) regimens. METHODS: A nationwide retrospective cohort from 42 health facilities was assessed for virological failure and development of HIVDR mutations. Data were collected at ART initiation and at 12 months of ART on patients with available HIV-1 viral load (VL) and ART adherence measurements. HIV resistance genotyping was performed on patients with VL ≥1000 copies/ml. Multiple logistic regression was used to determine factors associated with treatment failure. RESULTS: Of 828 patients, 66% were women, and the median age was 37 years. Of the 597 patients from whom blood samples were collected, 86.9% were virologically suppressed, while 11.9% were not. Virological failure was strongly associated with age <25 years (adjusted odds ratio [aOR]: 6.4; 95% confidence interval [CI]: 3.2-12.9), low adherence (aOR: 2.87; 95% CI: 1.5-5.0) and baseline CD4 counts <200 cells/µl (aOR 3.4; 95% CI: 1.9-6.2). Overall, 9.1% of all patients on ART had drug resistance mutations after 1 year of ART; 27% of the patients who failed treatment had no evidence of HIVDR mutations. HIVDR mutations were not observed in patients on the recommended second-line ART regimen in Rwanda. CONCLUSIONS: The last step of the UNAIDS 90-90-90 target appears within grasp, with some viral failures still due to non-adherence. Nonetheless, youth and late initiators are at higher risk of virological failure. Youth-focused programmes could help prevent further drug HIVDR development.

Factors Associated with Productive Recruiting in a Respondent-Driven Sample of Men who Have Sex with Men in Vancouver, Canada.

Respondent-driven sampling (RDS) has become a preferred sampling strategy for HIV research and surveillance in many global settings. Methodological investigation into the validity of RDS-generated samples has helped improve theoretical components of design. However, the operational challenges of implementing RDS remain underreported. We sought to identify factors independently associated with productive recruiting in an urban RDS-generated sample of gay, bisexual, and other men who have sex with men (MSM). Data were collected from the Momentum Health Study, a cohort of MSM recruited by RDS in Vancouver, Canada. Eligible men were given up to six RDS coupons to recruit their peers. The primary outcome was a count variable of each participant's number of eligible recruits. Multivariable Poisson regression identified independent predictors of productive recruitment. In total, 719 individuals comprised this analysis, of which 119 were seeds. The distribution of eligible recruits was right skewed, with 391 (54.4 %) having never recruited another participant and only eight participants (1.1 %) having recruited five. Significant, independent predictors of recruiting one additional participant included network size per ten unit increase (adjusted risk ratio [aRR] 1.03), being of Aboriginal race/ethnicity compared with White (aRR 1.51), being HIV-positive (aRR 1.31), being sexually active with only males (aRR 2.48), being single compared with common law/married (aRR 1.37), having recently read gay newspapers (aRR 1.58), having recently sought sex partners online (aRR 1.33) and being out to a male parent (aRR 1.30). This analysis demonstrates the importance of social network size in RDS adjustment, but also identifies other socio-demographic and behavioral variables that increased RDS coupon return, which may help researchers better operationalize the implementation of RDS.

Including Online-Recruited Seeds: A Respondent-Driven Sample of Men Who Have Sex With Men.

BACKGROUND: Technology has changed the way men who have sex with men (MSM) seek sex and socialize, which may impact the implementation of respondent-driven sampling (RDS) among this population. Initial participants (also known as seeds) are a critical consideration in RDS because they begin the recruitment chains. However, little information is available on how the online-recruited seeds may effect RDS implementation. OBJECTIVE: The objectives of this study were to compare (1) online-recruited versus offline-recruited seeds and (2) subsequent recruitment chains of online-recruited versus offline-recruited seeds. METHODS: Between 2012 and 2014, we recruited MSM using RDS in Vancouver, Canada. RDS weights were used with logistic regression to address each objective. RESULTS: A total of 119 seeds were used, 85 of whom were online-recruited seeds, to recruit an additional 600 MSM. Compared with offline-recruited seeds, online-recruited seeds were less likely to be HIV-positive (OR 0.34, 95% CI 0.13-0.88), to have attended a gay community group (AOR 0.33, 95% CI 0.12-0.90), and to feel gay community involvement was "very important" (AOR 0.16, 95% CI 0.03-0.93). Online-recruited seeds were more likely to ask a sexual partner's HIV status always versus <50% of the time (AOR 5.21, 95% CI 1.17-23.23), to have watched the Pride parade (AOR 6.30, 95% CI 1.69-23.45), and to have sought sex online (AOR 4.29, 95% CI 1.53-12-12.05). Further, compared with recruitment chains started by offline-recruited seeds, recruits from chains started by online-recruited seeds (283/600, 47.2%) were less likely to be HIV-positive (AOR 0.25, 95% CI 0.16-0.40), to report "versatile" versus "bottom" sexual position preference (AOR 0.56, 95% CI 0.35-0.88), and to be in a relationship lasting >1 year (AOR 1.65, 95% CI 1.06-2.56). Recruits of online seeds were more likely to be out as gay for longer (eg, 11-21 vs 1-4 years, AOR 2.22, 95% CI 1.27-3.88) and have fewer Facebook friends (eg, 201-500 vs >500, AOR 1.69, 95% CI 1.02-2.80). CONCLUSIONS: Online-recruited seeds were more prevalent, recruited fewer participants, but were different from those recruited offline. This may therefore help create a more diverse overall sample. Our work has shown the value of geosocial networking apps for aiding RDS recruitment efforts, especially when faced with slow participation uptake by other means. Understanding the degree to which networks interact will be an important next step in confirming the efficacy of online RDS recruitment strategies.

Improving health outcomes through concurrent HIV program scale-up and health system development in Rwanda: 20 years of experience.

The 1994 genocide against the Tutsi destroyed the health system in Rwanda. It is impressive that a small country like Rwanda has advanced its health system to the point of now offering near universal health insurance coverage. Through a series of strategic structural changes to its health system, catalyzed through international assistance, Rwanda has demonstrated a commitment towards improving patient and population health indicators. In particular, the rapid scale up of antiretroviral therapy (ART) has become a great success story for Rwanda. The country achieved universal coverage of ART at a CD4 cell count of 200 cells/mm(3) in 2007 and increased the threshold for initiation of ART to ≤350 cells/mm(3) in 2008. Further, 2013 guidelines raised the threshold for initiation to ≤500 cells/mm(3) and suggest immediate therapy for key affected populations. In 2015, guidelines recommend offering immediate treatment to all patients. By reviewing the history of HIV and the scale-up of treatment delivery in Rwanda since the genocide, this paper highlights some of the key innovations of the Government of Rwanda and demonstrates the ways in which the national response to the HIV epidemic has catalyzed the implementation of interventions that have helped strengthen the overall health system.

How do you circumcise a nation? The Rwandan case study.

Voluntary medical male circumcision has been conclusively demonstrated to reduce the lifetime risk of male acquisition of HIV. The strategy has been adopted as a component of a comprehensive strategy towards achieving an AIDS-free generation. A number of countries in which prevalence of HIV is high and circumcision is low have been identified as a priority, where innovative approaches to scale-up are currently being explored. Rwanda, as one of the priority countries, has faced a number of challenges to successful scale-up. We discuss here how simplifications in the procedure, addressing a lack of healthcare infrastructure and mobilizing resources, and engaging communities of both men and women have permitted Rwanda to move forward with more optimism in its scale-up tactics. Examples from Rwanda are used to highlight how these barriers can and should be addressed.

Factors associated with disclosure of HIV status among a cohort of individuals on antiretroviral therapy in British Columbia, Canada.

We sought to examine the prevalence and correlates of HIV-disclosure among treatment-experienced individuals in British Columbia, Canada. Study participants completed an interviewer-administered survey between July 2007 and January 2010. The primary outcome of interest was disclosing one's HIV-positive status to all new sexual partners within the last 6 months. An exploratory logistic regression model was developed to identify variables independently associated with disclosure. Of the 657 participants included in this analysis, 73.4 % disclosed their HIV-positive status to all of their sexual partners. Factors independently associated with non-disclosure included identifying as a woman (adjusted odds ratio [AOR] 1.92; 95 % confidence interval [95 % CI] 1.13-3.27) or as a gay or bisexual man (AOR 2.45; 95 % CI 1.47-4.10). Behaviours that were independently associated with non-disclosure were having sex with a stranger (AOR 2.74; 95 % CI 1.46-5.17), not being on treatment at the time of interview (AOR 2.67; 95 % CI 1.40-5.11), and not always using a condom (AOR 1.78; 95 % CI 1.09-2.90). Future preventative strategies should focus on environmental and social factors that may inhibit vulnerable HIV-positive populations, such as women and gay or bisexual men, from safely disclosing their positive status.

Impact of implementing performance-based financing on childhood malnutrition in Rwanda.

BACKGROUND: Malnutrition remains a serious concern in Rwanda, particularly among children under-5 years. Performance-based financing (PBF), an innovative health systems financing strategy, has been implemented at the national level since 2008. This study aimed to assess the impact of PBF and other factors associated with the prevalence of three classifications of malnutrition (stunting, wasting and underweight) in children under-5 years in Rwanda. METHODS: The study is a cross-sectional study comprising of 713 children under five years old from 557 households, whose anthropometric measurements (height, weight and age) had been obtained as part of the 2008 Rwanda General Health and HIV household survey. Z-scores for height-for-age, weight-for-age, weight-for-height, and body mass index-for-age were analyzed according to the World Health Organization 2006 Child Growth Standards. Random intercept logistic regression models were used to regress each anthropometric measure (WAZ, HAZ and WHZ) against child, maternal and household characteristics. RESULTS: Child participants ranged in age from 0 to 60 months, 20.2% of children were under 12 months and 5.1% were HIV positive. The prevalence of wasting was 8.8%; of stunting was 58.4%; and of underweight status was 20.7%. Maternal emotional and social wellbeing was protective of wasting in children under-5 years of age. Living in districts implementing PBF was protective of wasting (Adjusted Odds Ratio: 0.43; 95% confidence interval: 0.19-0.97). Living in a district with PBF was not found to be associated with either stunting or underweight status among children under-5. CONCLUSIONS: PBF may have a protective association with particular forms of malnutrition among children under-5 years in Rwanda. These findings warrant further investigation in relation to the impact of implementing innovative financing schemes on health outcomes.

Community mapping and respondent-driven sampling of gay and bisexual men's communities in Vancouver, Canada.

Literature suggests formative research is vital for those using respondent-driven sampling (RDS) to study hidden populations of interest. However, few authors have described in detail how different qualitative methodologies can address the objectives of formative research for understanding the social network properties of the study population, selecting seeds and adapting survey logistics to best fit the population. In this paper we describe the use of community mapping exercises as a tool within focus groups to collect data on social and sexual network characteristics of gay and bisexual men in the metropolitan area of Vancouver, Canada. Three key themes emerged from analysing community maps along with other formative research data: (1) connections between physical spaces and social networks of gay and bisexual men, (2) diversity in communities and (3) substance use linked to formation of sub-communities. We discuss how these themes informed the planning and operations of a longitudinal epidemiological cohort study recruited by RDS. We argue that using community mapping within formative research is a valuable qualitative tool for characterising network structures of a diverse and differentiated population of gay and bisexual men in a highly developed urban setting.

Matched vs Nonmatched Placebos in a Randomized Trial of COVID-19 Treatments.

Importance: Matched placebo interventions are complex and resource intensive. Recent evidence suggests matched placebos may not always be necessary. Previous studies have predominantly evaluated potential bias of nonmatched placebos (ie, differing on dose, frequency of administration, or formulation) in pain and mental health, but to date no systematic examination has been conducted in infectious disease. Objective: To test for differences between nonmatched and matched placebo arms with respect to clinical outcome measures across multiple therapeutics for COVID-19. Design, Setting, and Participants: In a comparative effectiveness research study, a post hoc analysis was conducted of data on individual patients enrolled in a large, multiarm, platform randomized clinical trial in symptomatic adult outpatients with COVID-19 between January 15, 2021, to September 28, 2023, in which the outcomes of both matched and nonmatched placebo groups were reported. Bayesian and frequentist covariate-adjusted techniques were compared with 7 intervention-placebo pairs. Exposures: Seven matched and nonmatched placebo pairs (for a total of 7 comparisons) were evaluated throughout the primary platform trial. Comparisons were made between treatment and its associated matched (concurrent) placebo, as well as with nonmatched placebo (alone and in combination) assessed at a similar time point. Main Outcomes and Measures: Outcomes assessed included hospitalizations, EuroQol 5-Dimension 5-level scores, and PROMIS Global-10 scores. Results: A total of 7 intervention-control pairs (N = 2684) were assessed, including 1620 (60.4%) women, with mean (SD) age, 47 (15.2) years; the most common comorbidities were obesity (41.9%) and hypertension (37.9%). In a meta-analysis with decoupled SEs, accounting for overlapping placebo patients, the overall odds ratio (OR) of nonmatched compared with matched placebo was 1.01 (95% credible interval, 0.77-1.32), with posterior probability of equivalence, defined as 0.8 ≤ OR ≤ 1.2 (a deviation from perfect equivalence ie, OR = 1, by no more than 0.2) of 85.4%, implying no significant difference. Unadjusted analysis of the event rate difference between all nonmatched and matched placebo groups did not identify any notable differences across all 7 treatment-placebo combinations assessed. Similar analysis that was conducted for patient-reported quality of life outcomes did not yield statistically significant differences. Conclusions and Relevance: In this post hoc study of a randomized clinical platform trial, pooling matched and nonmatched placebo patient data did not lead to inconsistencies in treatment effect estimation for any of the investigational drugs. These findings may have significant implications for future platform trials, as the use of nonmatched placebo may improve statistical power, or reduce barriers to placebo implementation.

Identifying self-perceived HIV-related stigma in a population accessing antiretroviral therapy.

This study identifies factors associated with self-perceived HIV-related stigma (stigma) among a cohort of individuals accessing antiretroviral therapy in British Columbia, Canada. Data were drawn from the Longitudinal Investigations into Supportive and Ancillary Health Services study, which collects social, clinical, and quality of life (QoL) information through an interviewer-administered survey. Clinical variables (i.e., CD4 count) were obtained through linkages with the British Columbia HIV/AIDS Drug Treatment Program. Multivariable linear regression was performed to determine the independent predictors of stigma. Our results indicate that among participants with high school education or greater the outcome stigma was associated with a 3.05 stigma unit decrease (95% CI: -5.16, -0.93). Having higher relative standard of living and perceiving greater neighborhood cohesion were also associated with a decrease in stigma (-5.30 95% CI: -8.16, -2.44; -0.80 95% CI: -1.39, -0.21, respectively). Lower levels of stigma were found to be associated with better QoL measures, including perceiving better overall function (-0.90 95% CI: -1.47, -0.34), having fewer health worries (-2.11 95% CI: -2.65, -1.57), having fewer financial worries (-0.67 95% CI: -1.12, -0.23), and having less HIV disclosure concerns (-4.12 95% CI: -4.63, -3.62). The results of this study show that participants with higher education level, better QoL measures, and higher self-reported standards of living are less likely to perceive HIV-related stigma.

Early Treatment with Fluvoxamine among Patients with COVID-19: A Cost-Consequence Model.

To date, two published randomized trials have indicated a clinical benefit of early treatment with fluvoxamine versus placebo for adults with symptomatic COVID-19. Using the results of the largest of these trials, the TOGETHER trial, we conducted a cost-consequence analysis to assess the health system benefits of preventing progression to severe COVID-19 in outpatient populations in the United States. A decision-analytic model in the form of a decision tree was constructed to evaluate two treatment strategies for high-risk patients with confirmed, symptomatic COVID-19 in the primary analysis: treatment with a 10-day course of fluvoxamine (100 mg twice daily) and current standard-of-care. A secondary analysis comparing a 5-day course of nirmatrelvir-ritonavir was also conducted. We used a time horizon of 28 days. Reported outcomes included cost-savings and hospitalization days avoided. The results of our analysis indicated that administration of fluvoxamine to symptomatic outpatients at high risk of progressing to severe COVID-19 was substantially cost-saving, in the amount of $232 per eligible patient and prevented an average of 0.15 hospital days per patient treated, compared with standard of care. Nirmatrelvir-ritonavir was also shown to be cost-saving despite its higher acquisition cost and provided savings to the healthcare system of $625 per patient treated. These findings suggest that fluvoxamine is likely to be a cost-effective addition to frontline COVID-19 mitigation strategies in many settings, particularly where access to nirmaltrevir-ritonavir or monoclonal antibodies is limited.

Factors predictive of 30-day postoperative mortality in HIV/AIDS patients in the era of highly active antiretroviral therapy.

BACKGROUND: Factors that predict HIV (human immunodeficiency virus)/AIDS patient postoperative mortality have remained poorly defined. OBJECTIVES: The primary objective of this study was to identify factors predictive of short-term, postoperative mortality in HIV/AIDS patients. The secondary objective of this study was to develop a scoring system that would predict short-term postoperative mortality in HIV/AIDS patients. METHODS: We retrospectively reviewed all HIV/AIDS patients who underwent surgical procedures in British Columbia, Canada, between April 1995 and March 2002. The primary outcome evaluated was 30-day postoperative mortality. Demographic, clinical, and hospitalization-related data were obtained and utilized to predict outcomes using a logistic regression model. RESULTS: A total of 2305 procedures were carried out on 1322 patients during the study period. Admissions were classified as urgent/emergent for 1311 procedures (57%) and the overall 30-day postoperative mortality was 9.5% (126 deaths). Urgent/emergent admission, older age, prior surgery, a CD4 cell count of ≤ 50 cells/mm, a hemoglobin level ≤ 120 g/L, and a white blood cell count >11 g/L within 90 days before the surgical procedure was predictive of an increased 30-day postoperative mortality in a multivariate model. Using these variables, we formulated the HIV Surgical Mortality Score (HSMS) to obtain the median-estimated probability of postoperative death. CONCLUSIONS: For accurate preoperative mortality risk stratification for HIV/AIDS patients, we have found that several clinical and laboratory variables must be evaluated. If appropriately validated, our proposed HSMS could be utilized to estimate the probability of short-term postoperative death among HIV/AIDS patients.

Fluvoxamine for the Early Treatment of COVID-19: A Meta-analysis of Randomized Clinical Trials.

Fluvoxamine is widely prescribed as an antidepressant. Recent studies show the drug may have a clinical benefit in treating COVID-19. We aimed to perform a meta-analysis of the existing randomized trials of fluvoxamine compared with placebo on the early treatment of COVID-19 patients. We included only randomized clinical trials enrolling ambulatory patients with early-stage disease (symptoms > 7 days) for the prevention of hospitalization. We searched MEDLINE, and clinicaltrials.gov databases to identify trials and extract data with clarifications from the study investigators. We performed a fixed-effects meta-analysis and sensitivity analyses via R to evaluate the pooled estimate of hospitalization. We included three randomized trials: STOP COVID 1 and 2, and the TOGETHER Trial. The studies included a total of 2,196 patients. The STOP COVID trials measured clinical deterioration whereas the TOGETHER Trial measured hospitalization as the primary outcome. All trials reported on hospitalization up to day 28. The meta-analysis results show that patients receiving fluvoxamine were 31% less likely to experience clinical deterioration or hospitalization compared with placebo (risk ratio, 0.69; 95% CI, 0.54-0.88). A sensitivity analysis using the definition of hospitalization resulted in a risk reduction of 21% (95% CI, 0.60-1.03). Data from three randomized controlled trials show that fluvoxamine was associated with a reduction in the primary outcome measure (either clinical deterioration or composite outcome of hospitalization or extended emergency setting observation), although analysis of hospitalization-only was not statistically significant. More evidence from future trials is still needed to support the findings of this meta-analysis.