Inhaled Fluticasone Furoate for Outpatient Treatment of Covid-19.

BACKGROUND: The effectiveness of inhaled glucocorticoids in shortening the time to symptom resolution or preventing hospitalization or death among outpatients with mild-to-moderate coronavirus disease 2019 (Covid-19) is unclear. METHODS: We conducted a decentralized, double-blind, randomized, placebo-controlled platform trial in the United States to assess the use of repurposed medications in outpatients with confirmed coronavirus disease 2019 (Covid-19). Nonhospitalized adults 30 years of age or older who had at least two symptoms of acute infection that had been present for no more than 7 days before enrollment were randomly assigned to receive inhaled fluticasone furoate at a dose of 200 µg once daily for 14 days or placebo. The primary outcome was the time to sustained recovery, defined as the third of 3 consecutive days without symptoms. Key secondary outcomes included hospitalization or death by day 28 and a composite outcome of the need for an urgent-care or emergency department visit or hospitalization or death through day 28. RESULTS: Of the 1407 enrolled participants who underwent randomization, 715 were assigned to receive inhaled fluticasone furoate and 692 to receive placebo, and 656 and 621, respectively, were included in the analysis. There was no evidence that the use of fluticasone furoate resulted in a shorter time to recovery than placebo (hazard ratio, 1.01; 95% credible interval, 0.91 to 1.12; posterior probability of benefit [defined as a hazard ratio >1], 0.56). A total of 24 participants (3.7%) in the fluticasone furoate group had urgent-care or emergency department visits or were hospitalized, as compared with 13 participants (2.1%) in the placebo group (hazard ratio, 1.9; 95% credible interval, 0.8 to 3.5). Three participants in each group were hospitalized, and no deaths occurred. Adverse events were uncommon in both groups. CONCLUSIONS: Treatment with inhaled fluticasone furoate for 14 days did not result in a shorter time to recovery than placebo among outpatients with Covid-19 in the United States. (Funded by the National Center for Advancing Translational Sciences and others; ACTIV-6 ClinicalTrials.gov number, NCT04885530.).

Tree-based subgroup discovery using electronic health record data: heterogeneity of treatment effects for DTG-containing therapies.

The rich longitudinal individual level data available from electronic health records (EHRs) can be used to examine treatment effect heterogeneity. However, estimating treatment effects using EHR data poses several challenges, including time-varying confounding, repeated and temporally non-aligned measurements of covariates, treatment assignments and outcomes, and loss-to-follow-up due to dropout. Here, we develop the subgroup discovery for longitudinal data algorithm, a tree-based algorithm for discovering subgroups with heterogeneous treatment effects using longitudinal data by combining the generalized interaction tree algorithm, a general data-driven method for subgroup discovery, with longitudinal targeted maximum likelihood estimation. We apply the algorithm to EHR data to discover subgroups of people living with human immunodeficiency virus who are at higher risk of weight gain when receiving dolutegravir (DTG)-containing antiretroviral therapies (ARTs) versus when receiving non-DTG-containing ARTs.

HIV Incidence and Death Among Orphaned and Nonorphaned Children and Adolescents Living in Family-Based Settings in Western Kenya: A Prospective Cohort Analysis.

OBJECTIVE: To compare the incidence of HIV, death, and abuse among orphaned children to nonorphaned children living in households caring for orphaned children in Western Kenya. STUDY DESIGN: A random sample was taken of 300 households caring for at least one orphaned child in Uasin Gishu County, Kenya. All orphaned and nonorphaned children in each selected household were enrolled in a prospective cohort study between 2010 and 2013. A total of 1488 children (487 double orphans, 743 single orphans, and 258 nonorphans) were followed up annually until 2019. Survival analysis was used to estimate hazard ratios and 95% confidence intervals (CIs) of the association between the number of parents the child had lost (none, 1, or 2), and HIV incidence, death, combined HIV incidence or death, and incident abuse. RESULTS: Among 1488 children enrolled, 52% of participants were females, 23 were HIV positive, and the median age was 10.4 years. Over the course of the study, 16 orphaned children died and 11 acquired HIV. No deaths or incident HIV infections were observed among the nonorphaned children. Among children who were HIV negative at enrollment, loss of a parent was strongly associated with incident HIV (adjusted hazard ratio: 2.21 per parent lost, 95% CI: 1.03-4.73) and HIV or death (adjusted hazard ratio: 2.46 per parent lost, 95% CI: 1.37-4.42). There were no significant associations between orphan level and abuse. CONCLUSIONS: In similar households, orphaned children experience a higher risk of HIV and death than nonorphaned children. Both orphaned children and the families caring for them need additional support to prevent adverse health outcomes.

Characterization of HIV-Related Stigma in Myanmar.

Characterizing HIV-related stigma and its impacts are important for interventions toward their elimination. A cross-sectional study was conducted in 2016 to evaluate enacted and internalized stigma among adult people living with HIV (PLWH) across four cities in Myanmar using the India Stigma Index questionnaire. Multivariable regression analyses were performed to determine differences in measured enacted and internalized stigma outcomes. Among 1,006 participants, 89% reported any stigma indicator, 47% enacted stigma, and 87% internalized stigma. In regression analysis, city and duration of illness were associated with higher enacted stigma, and younger age was associated with higher internalized stigma. Those with HIV duration > 7.4 years had mean enacted stigma nearly 2 units higher than the overall mean. Internalized stigma increased with duration of illness and leveled off at 5 years. PLWH from smaller cities experienced lower stigma. In Myanmar, nearly 90% of PLWH experience stigma, results that reflect a unique transition point.

Effect of Fluvoxamine vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19: A Randomized Clinical Trial.

Importance: The effectiveness of fluvoxamine to shorten symptom duration or prevent hospitalization among outpatients with mild to moderate symptomatic COVID-19 is unclear. Objective: To evaluate the efficacy of low-dose fluvoxamine (50 mg twice daily) for 10 days compared with placebo for the treatment of mild to moderate COVID-19 in the US. Design, Setting, and Participants: The ongoing Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV-6) platform randomized clinical trial was designed to test repurposed medications in outpatients with mild to moderate COVID-19. A total of 1288 participants aged 30 years or older with test-confirmed SARS-CoV-2 infection and experiencing 2 or more symptoms of acute COVID-19 for 7 days or less were enrolled between August 6, 2021, and May 27, 2022, at 91 sites in the US. Interventions: Participants were randomized to receive 50 mg of fluvoxamine twice daily for 10 days or placebo. Main Outcomes and Measures: The primary outcome was time to sustained recovery (defined as the third day of 3 consecutive days without symptoms). There were 7 secondary outcomes, including a composite outcome of hospitalization, urgent care visit, emergency department visit, or death through day 28. Results: Among 1331 participants who were randomized (median age, 47 years [IQR, 38-57 years]; 57% were women; and 67% reported receiving ≥2 doses of a SARS-CoV-2 vaccine), 1288 completed the trial (674 in the fluvoxamine group and 614 in the placebo group). The median time to sustained recovery was 12 days (IQR, 11-14 days) in the fluvoxamine group and 13 days (IQR, 12-13 days) in the placebo group (hazard ratio [HR], 0.96 [95% credible interval, 0.86-1.06], posterior P = .21 for the probability of benefit [determined by an HR >1]). For the composite outcome, 26 participants (3.9%) in the fluvoxamine group were hospitalized, had an urgent care visit, had an emergency department visit, or died compared with 23 participants (3.8%) in the placebo group (HR, 1.1 [95% credible interval, 0.5-1.8], posterior P = .35 for the probability of benefit [determined by an HR <1]). One participant in the fluvoxamine group and 2 participants in the placebo group were hospitalized; no deaths occurred in either group. Adverse events were uncommon in both groups. Conclusions and Relevance: Among outpatients with mild to moderate COVID-19, treatment with 50 mg of fluvoxamine twice daily for 10 days, compared with placebo, did not improve time to sustained recovery. These findings do not support the use of fluvoxamine at this dose and duration in patients with mild to moderate COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04885530.

Effect of Higher-Dose Ivermectin for 6 Days vs Placebo on Time to Sustained Recovery in Outpatients With COVID-19: A Randomized Clinical Trial.

Importance: It is unknown whether ivermectin, with a maximum targeted dose of 600 µg/kg, shortens symptom duration or prevents hospitalization among outpatients with mild to moderate COVID-19. Objective: To evaluate the effectiveness of ivermectin at a maximum targeted dose of 600 µg/kg daily for 6 days, compared with placebo, for the treatment of early mild to moderate COVID-19. Design, Setting, and Participants: The ongoing Accelerating COVID-19 Therapeutic Interventions and Vaccines 6 (ACTIV-6) platform randomized clinical trial was designed to evaluate repurposed therapies among outpatients with mild to moderate COVID-19. A total of 1206 participants older than 30 years with confirmed COVID-19 experiencing at least 2 symptoms of acute infection for less than or equal to 7 days were enrolled at 93 sites in the US from February 16, 2022, through July 22, 2022, with follow-up data through November 10, 2022. Interventions: Participants were randomly assigned to receive ivermectin, with a maximum targeted dose of 600 µg/kg (n = 602) daily, or placebo (n = 604) for 6 days. Main Outcomes and Measures: The primary outcome was time to sustained recovery, defined as at least 3 consecutive days without symptoms. The 7 secondary outcomes included a composite of hospitalization, death, or urgent/emergent care utilization by day 28. Results: Among 1206 randomized participants who received study medication or placebo, the median (IQR) age was 48 (38-58) years, 713 (59.1%) were women, and 1008 (83.5%) reported receiving at least 2 SARS-CoV-2 vaccine doses. The median (IQR) time to sustained recovery was 11 (11-12) days in the ivermectin group and 11 (11-12) days in the placebo group. The hazard ratio (posterior probability of benefit) for improvement in time to recovery was 1.02 (95% credible interval, 0.92-1.13; P = .68). Among those receiving ivermectin, 34 (5.7%) were hospitalized, died, or had urgent or emergency care visits compared with 36 (6.0%) receiving placebo (hazard ratio, 1.0 [95% credible interval, 0.6-1.5]; P = .53). In the ivermectin group, 1 participant died and 4 were hospitalized (0.8%); 2 participants (0.3%) were hospitalized in the placebo group and there were no deaths. Adverse events were uncommon in both groups. Conclusions and Relevance: Among outpatients with mild to moderate COVID-19, treatment with ivermectin, with a maximum targeted dose of 600 µg/kg daily for 6 days, compared with placebo did not improve time to sustained recovery. These findings do not support the use of ivermectin in patients with mild to moderate COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04885530.

Higher-Dose Fluvoxamine and Time to Sustained Recovery in Outpatients With COVID-19: The ACTIV-6 Randomized Clinical Trial.

Importance: The effect of higher-dose fluvoxamine in reducing symptom duration among outpatients with mild to moderate COVID-19 remains uncertain. Objective: To assess the effectiveness of fluvoxamine, 100 mg twice daily, compared with placebo, for treating mild to moderate COVID-19. Design, Setting, and Participants: The ACTIV-6 platform randomized clinical trial aims to evaluate repurposed medications for mild to moderate COVID-19. Between August 25, 2022, and January 20, 2023, a total of 1175 participants were enrolled at 103 US sites for evaluating fluvoxamine; participants were 30 years or older with confirmed SARS-CoV-2 infection and at least 2 acute COVID-19 symptoms for 7 days or less. Interventions: Participants were randomized to receive fluvoxamine, 50 mg twice daily on day 1 followed by 100 mg twice daily for 12 additional days (n = 601), or placebo (n = 607). Main Outcomes and Measures: The primary outcome was time to sustained recovery (defined as at least 3 consecutive days without symptoms). Secondary outcomes included time to death; time to hospitalization or death; a composite of hospitalization, urgent care visit, emergency department visit, or death; COVID-19 clinical progression scale score; and difference in mean time unwell. Follow-up occurred through day 28. Results: Among 1208 participants who were randomized and received the study drug, the median (IQR) age was 50 (40-60) years, 65.8% were women, 45.5% identified as Hispanic/Latino, and 76.8% reported receiving at least 2 doses of a SARS-CoV-2 vaccine. Among 589 participants who received fluvoxamine and 586 who received placebo included in the primary analysis, differences in time to sustained recovery were not observed (adjusted hazard ratio [HR], 0.99 [95% credible interval, 0.89-1.09]; P for efficacy = .40]). Additionally, unadjusted median time to sustained recovery was 10 (95% CI, 10-11) days in both the intervention and placebo groups. No deaths were reported. Thirty-five participants reported health care use events (a priori defined as death, hospitalization, or emergency department/urgent care visit): 14 in the fluvoxamine group compared with 21 in the placebo group (HR, 0.69 [95% credible interval, 0.27-1.21]; P for efficacy = .86) There were 7 serious adverse events in 6 participants (2 with fluvoxamine and 4 with placebo) but no deaths. Conclusions and Relevance: Among outpatients with mild to moderate COVID-19, treatment with fluvoxamine does not reduce duration of COVID-19 symptoms. Trial Registration: ClinicalTrials.gov Identifier: NCT04885530.

Effect of care environment on educational attainment among orphaned and separated children and adolescents in Western Kenya.

BACKGROUND: There are approximately 140 million orphaned and separated children (OSCA) around the world. In Kenya, many of these children live with extended family while others live in institutions. Despite evidence that orphans are less likely to be enrolled in school than non-orphans, there is little evidence regarding the role of care environment. This evidence is vital for designing programs and policies that promote access to education for orphans, which is not only their human right but also an important social determinant of health. The purpose of this study was to compare educational attainment among OSCA living in Charitable Children's Institutions and family-based settings in Uasin Gishu County, Kenya. METHODS: This study analyses follow up data from a cohort of OSCA living in 300 randomly selected households and 17 institutions. We used Poisson regression to estimate the effect of care environment on primary school completion among participants age ≥ 14 as well as full and partial secondary school completion among participants age ≥ 18. Risk ratios and 95% confidence intervals were estimated using a bootstrap method with 1000 replications. RESULTS: The analysis included 1406 participants (495 from institutions, 911 from family-based settings). At baseline, 50% were female, the average age was 9.5 years, 54% were double orphans, and 3% were HIV-positive. At follow-up, 76% of participants age ≥ 14 had completed primary school and 32% of participants age ≥ 18 had completed secondary school. Children living in institutions were significantly more likely to complete primary school (aRR: 1.18, 95% CI: 1.10-1.28) and at least 1 year of secondary school (aRR: 1.28, 95% CI: 1.18-1.39) than children in family-based settings. Children living in institutions were less likely to have completed all 4 years secondary school (aRR: 0.79, 95% CI: 0.43-1.18) than children in family-based settings. CONCLUSION: Children living in institutional environments were more likely to complete primary school and some secondary school than children living in family-based care. Further support is needed for all orphans to improve primary and secondary school completion. Policies that require orphans to leave institution environments upon their eighteenth birthday may be preventing these youth from completing secondary school.

Individualized Assessment of Risk of Complications after Benign Hysterectomy.

STUDY OBJECTIVES: The primary objective of this study is to identify patient characteristics associated with postoperative complications or readmissions after hysterectomy for a benign indication. DESIGN: Retrospective cohort. SETTING: The Surgical Gynecologic Scorecard Database includes performance metrics and patient outcomes for hysterectomies across 7 sites in Ontario, Canada. PARTICIPANTS: Individuals who underwent hysterectomy for benign gynecologic indication and were recorded in the Surgical Gynecologic Scorecard Database between July 2016 and June 2019 were included in this study. MEASUREMENTS AND MAIN RESULTS: Two outcomes of interest were considered: (1) complications grade II or greater on the Clavien-Dindo classification scale and (2) emergency room visits or hospital readmissions within 6 weeks after operation. Logistic models were generated to determine the associations between outcome of interest and potential predictors using a mixed-step AIC selection algorithm. A total of 2792 patients underwent hysterectomy for a benign indication during the study period, with a mean age of 52.6 ± 11.7 years and mean body mass index of 29.0 ± 0.7 kg/m2. The most common indications for surgery were abnormal uterine bleeding (33.3%) and myomas (33.6%). Previous cesarean delivery (adjusted odds ratio [aOR], 1.22; 95% confidence interval [CI], 1.04-1.42), American Society of Anesthesiologists class ≥3 (aOR, 2.31; 95% CI, 1.42-3.99), preoperative anemia (aOR, 1.51; 95% CI, 1.12-2.02), and laparotomic approach (aOR, 1.73; 95% CI, 1.30-2.29) were associated with increased odds of complication. Perioperative complications (aOR, 2.95; 95% CI, 2.12-4.08), preoperative anemia (aOR, 1.43; 95% CI, 1.03-1.98), and vaginal (aOR, 1.94; 95% CI, 1.26-2.96) or laparotomic (aOR, 1.64; 95% CI, 1.10-2.43) approach were associated with increased odds of emergency room visit or readmission to hospital. CONCLUSION: This study identified several important risk factors for complications after hysterectomy. The utility of these data is important to help improve counseling for patients undergoing a hysterectomy and potentially optimize modifiable risk factors when identified preoperatively.

Effect of Ivermectin vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19: A Randomized Clinical Trial.

Importance: The effectiveness of ivermectin to shorten symptom duration or prevent hospitalization among outpatients in the US with mild to moderate symptomatic COVID-19 is unknown. Objective: To evaluate the efficacy of ivermectin, 400 µg/kg, daily for 3 days compared with placebo for the treatment of early mild to moderate COVID-19. Design, Setting, and Participants: ACTIV-6, an ongoing, decentralized, double-blind, randomized, placebo-controlled platform trial, was designed to evaluate repurposed therapies in outpatients with mild to moderate COVID-19. A total of 1591 participants aged 30 years and older with confirmed COVID-19, experiencing 2 or more symptoms of acute infection for 7 days or less, were enrolled from June 23, 2021, through February 4, 2022, with follow-up data through May 31, 2022, at 93 sites in the US. Interventions: Participants were randomized to receive ivermectin, 400 µg/kg (n = 817), daily for 3 days or placebo (n = 774). Main Outcomes and Measures: Time to sustained recovery, defined as at least 3 consecutive days without symptoms. There were 7 secondary outcomes, including a composite of hospitalization or death by day 28. Results: Among 1800 participants who were randomized (mean [SD] age, 48 [12] years; 932 women [58.6%]; 753 [47.3%] reported receiving at least 2 doses of a SARS-CoV-2 vaccine), 1591 completed the trial. The hazard ratio (HR) for improvement in time to recovery was 1.07 (95% credible interval [CrI], 0.96-1.17; posterior P value [HR >1] = .91). The median time to recovery was 12 days (IQR, 11-13) in the ivermectin group and 13 days (IQR, 12-14) in the placebo group. There were 10 hospitalizations or deaths in the ivermectin group and 9 in the placebo group (1.2% vs 1.2%; HR, 1.1 [95% CrI, 0.4-2.6]). The most common serious adverse events were COVID-19 pneumonia (ivermectin [n = 5]; placebo [n = 7]) and venous thromboembolism (ivermectin [n = 1]; placebo [n = 5]). Conclusions and Relevance: Among outpatients with mild to moderate COVID-19, treatment with ivermectin, compared with placebo, did not significantly improve time to recovery. These findings do not support the use of ivermectin in patients with mild to moderate COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04885530.

Sex differences in health status, healthcare utilization, and costs among individuals with elevated blood pressure: the LARK study from Western Kenya.

BACKGROUND: Elevated blood pressure is the leading risk factor for global mortality. While it is known that there exist differences between men and women with respect to socioeconomic status, self-reported health, and healthcare utilization, there are few published studies from Africa. This study therefore aims to characterize differences in self-reported health status, healthcare utilization, and costs between men and women with elevated blood pressure in Kenya. METHODS: Data from 1447 participants enrolled in the LARK Hypertension study in western Kenya were analyzed. Latent class analysis based on five dependent variables was performed to describe patterns of healthcare utilization and costs in the study population. Regression analysis was then performed to describe the relationship between different demographics and each outcome. RESULTS: Women in our study had higher rates of unemployment (28% vs 12%), were more likely to report lower monthly earnings (72% vs 51%), and had more outpatient visits (39% vs 28%) and pharmacy prescriptions (42% vs 30%). Women were also more likely to report lower quality-of-life and functional health status, including pain, mobility, self-care, and ability to perform usual activities. Three patterns of healthcare utilization were described: (1) individuals with low healthcare utilization, (2) individuals who utilized care and paid high out-of-pocket costs, and (3) individuals who utilized care but had lower out-of-pocket costs. Women and those with health insurance were more likely to be in the high-cost utilizer group. CONCLUSIONS: Men and women with elevated blood pressure in Kenya have different health care utilization behaviors, cost and economic burdens, and self-perceived health status. Awareness of these sex differences can help inform targeted interventions in these populations.

HIV prevalence in young people and children living on the streets, Kenya.

OBJECTIVE: To obtain an estimate of the size of, and human immunodeficiency (HIV) prevalence among, young people and children living on the streets of Eldoret, Kenya. METHODS: We counted young people and children using a point-in-time approach, ensuring we reached our target population by engaging relevant community leaders during the planning of the study. We acquired point-in-time count data over a period of 1 week between the hours of 08:00 and 23:00, from both a stationary site and by mobile teams. Participants provided demographic data and a fingerprint (to avoid double-counting) and were encouraged to speak with an HIV counsellor and undergo HIV testing. We used a logistic regression model to test for an association between age or sex and uptake of HIV testing and seropositivity. FINDINGS: Of the 1419 eligible participants counted, 1049 (73.9%) were male with a median age of 18 years. Of the 1029 who spoke with a counsellor, 1004 individuals accepted HIV counselling and 947 agreed to undergo an HIV test. Combining those who were already aware of their HIV-positive status with those who were tested during our study resulted in an overall HIV seroprevalence of 4.1%. The seroprevalence was 2.7% (19/698) for males and 8.9% (23/259) for females. We observed an increase in seroprevalence with increasing age for both sexes, but of much greater magnitude for females. CONCLUSION: By counting young people and children living on the streets and offering them HIV counselling and testing, we could obtain population-based estimates of HIV prevalence.

Estimation of cumulative number of post-treatment Lyme disease cases in the US, 2016 and 2020.

BACKGROUND: Lyme disease (LD) is an infectious multi-system illness caused by the bacterial genus Borrelia and spread by bites of infected ticks. Although most patients are successfully treated by timely antibiotic therapy, it is broadly accepted that a sizeable number of patients experience treatment failure and continue to suffer long-term, debilitating symptoms, including pain, fatigue, cognitive dysfunction and other symptoms. This is known as post-treatment LD (PTLD), for which diagnosis is not standardized and treatment remains controversial. The prevalence and societal burden of PTLD is unknown. METHODS: In an effort to help characterize the LD landscape, we estimated the number of PTLD cases in the US in 2016 and 2020 using Monte-Carlo simulation techniques, publically-available demographic datasets, uncertainty in the inputs and realistic assumptions about incidence and treatment failure rates. RESULTS: Depending on the input assumptions, PTLD prevalence estimates for 2016 ranged from 69,011 persons (95% CI 51,796 to 89,312) to 1,523,869 (CI 1,268,634 to 1,809,416). Prevalence in 2020 is predicted to be higher than 2016, and may be as high as 1,944,189 (CI 1,619,988 to 2,304,147) cases. CONCLUSIONS: The cumulative prevalence of PLTD in the United States is estimated to be high and continues to increase. These findings will be of interest to epidemiologists and health economists studying disease burden in the US and elsewhere, and justify funding to study PTLD diagnosis and treatment.

High discordance in blood and genital tract HIV-1 drug resistance in Indian women failing first-line therapy.

Objectives: Examine HIV-1 plasma viral load (PVL) and genital tract (GT) viral load (GVL) and drug resistance in India. Methods: At the YRG Centre for AIDS Research and Education, Chennai, we tested: PVL in women on first-line ART for ≥6 months; GVL when PVL >2000 copies/mL; and plasma, genital and proviral reverse transcriptase drug resistance when GVL >2000 copies/mL. Wilcoxon rank-sum and Fisher's exact tests were used to identify failure and resistance associations. Pearson correlations were calculated to evaluate PVL-GVL associations. Inter-compartmental resistance discordance was evaluated using generalized estimating equations. Results: Of 200 women, 37% had detectable (>400 copies/mL) PVL and 31% had PVL >1000 copies/mL. Of women with detectable PVL, 74% had PVL >2000 copies/mL, of which 74% had detectable GVL. Higher PVL was associated with higher GVL. Paired plasma and genital sequences were available for 21 women; mean age of 34 years, median ART duration of 33 months, median CD4 count of 217 cells/mm3, median PVL of 5.4 log10 copies/mL and median GVL of 4.6 log10 copies/mL. Drug resistance was detected in 81%-91% of samples and 67%-76% of samples had dual-class resistance. Complete three-compartment concordance was seen in only 10% of women. GT-proviral discordance was significantly larger than plasma-proviral discordance. GT or proviral mutations discordant from plasma led to clinically relevant resistance in 24% and 30%, respectively. Conclusions: We identified high resistance and high inter-compartmental resistance discordance in Indian women, which might lead to unrecognized resistance transmission and re-emergence compromising treatment outcomes, particularly relevant to countries like India, where sexual HIV transmission is predominant.

Bridging Income Generation with Group Integrated Care for cardiovascular risk reduction: Rationale and design of the BIGPIC study.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of mortality worldwide, with >80% of CVD deaths occurring in low and middle income countries (LMICs). Diabetes mellitus and pre-diabetes are risk factors for CVD, and CVD is the major cause of morbidity and mortality among individuals with DM. There is a critical period now during which reducing CVD risk among individuals with diabetes and pre-diabetes may have a major impact. Cost-effective, culturally appropriate, and context-specific approaches are required. Two promising strategies to improve health outcomes are group medical visits and microfinance. METHODS/DESIGN: This study tests whether group medical visits integrated into microfinance groups are effective and cost-effective in reducing CVD risk among individuals with diabetes or at increased risk for diabetes in western Kenya. An initial phase of qualitative inquiry will assess contextual factors, facilitators, and barriers that may impact integration of group medical visits and microfinance for CVD risk reduction. Subsequently, we will conduct a four-arm cluster randomized trial comparing: (1) usual clinical care, (2) usual clinical care plus microfinance groups only, (3) group medical visits only, and (4) group medical visits integrated into microfinance groups. The primary outcome measure will be 1-year change in systolic blood pressure, and a key secondary outcome measure is 1-year change in overall CVD risk as measured by the QRISK2 score. We will conduct mediation analysis to evaluate the influence of changes in social network characteristics on intervention outcomes, as well as moderation analysis to evaluate the influence of baseline social network characteristics on effectiveness of the interventions. Cost-effectiveness analysis will be conducted in terms of cost per unit change in systolic blood pressure, percent change in CVD risk score, and per disability-adjusted life year saved. DISCUSSION: This study will provide evidence regarding effectiveness and cost-effectiveness of interventions to reduce CVD risk. We aim to produce generalizable methods and results that can provide a model for adoption in low-resource settings worldwide.

The Orthopedic Trauma Symposium: improving care of orthopedic injuries in Haiti.

BACKGROUND: Although single-trip volunteer medical teams can provide much-needed acute trauma care following natural disasters, their ability to leave a legacy of improved care in the region is often limited. One way to improve treatment of traumatic injuries is through conference-based teaching, such as the Orthopedic Trauma Symposium (OTS), which took place in Haiti in 2014. However, there is little research evaluating the effectiveness of such teaching tools. We evaluated the OTS and the potential benefits of future iterations of the course. METHODS: A survey consisting of 5-point Likert scale questions as well as qualitative open feedback assessed respondents' opinions regarding the value, content and delivery of the OTS. Respondents were classified dichotomously in terms of their role in the OTS (instructor v. participant) to measure any meaningful difference in feedback. RESULTS: In total, 84% of all participants agreed that course content was clearly communicated, and 98% agreed that instructors were knowledgeable in the topics covered. Moreover, 87% of all participants responded that they would apply the training in their medical practices going forward. CONCLUSION: Haitian physicians, residents and medical students responded favourably to the OTS. Open-ended questions offered concise, attainable improvements for future iterations of the course. Organizations committed to improving medical care in low- and middle-income countries should take note of these findings while continuing to develop the OTS and similar initiatives globally.

CONTEXTE: Les équipes médicales bénévoles qui font des interventions ponctuelles sont en mesure de prodiguer des soins essentiels en traumatologie aigüe après des désastres naturels, mais elles laissent souvent un héritage limité pour ce qui est de l'amélioration des soins dans la région touchée. Or, il est possible d'améliorer le traitement des blessures post-traumatismes par le biais de conférences didactiques, telles que le Symposium de traumatologie-orthopédie (STO) tenu en Haïti en 2014. Peu de recherches ont toutefois mesuré l'efficacité de ce type d'outil didactique. Nous avons voulu faire un bilan du STO et des avantages potentiels qu'il y aurait à répéter l'expérience. MÉTHODES: Un questionnaire prenant la forme d'une échelle de Likert en 5 points, ainsi que des questions qualitatives ouvertes, ont permis de recueillir l'opinion des répondeurs au sujet de l'utilité, du contenu et du déroulement du STO. Nous avons scindé les répondeurs en 2 groupes en fonction de leur rôle lors du STO (soit instructeurs, soit participants) pour mesurer les différences notables sur le plan des perceptions. RÉSULTATS: En tout, 84 % de l'ensemble des participants ont affirmé que le contenu du cours avait été clairement communiqué et 98 % ont affirmé que les instructeurs connaissaient les thèmes abordés. En outre, 87 % de tous les participants ont répondu avoir l'intention d'appliquer dorénavant la formation à leur pratique médicale. CONCLUSION: Les médecins, résidents et étudiants en médecine haïtiens ont répondu favorablement au STO. Les questions ouvertes ont suscité des suggestions concises et réalistes pour améliorer les futures éditions du cours. Les organisations vouées à l'amélioration des soins médicaux dans les pays à revenu faible et moyen devraient prendre note de ces observations tout en continuant d'exploiter la formule des STO et autres initiatives similaires ailleurs dans le monde.

Antiretroviral treatment failure, drug resistance, and subtype diversity in the only pediatric HIV clinic in Rhode Island.

BACKGROUND: Drug resistance development in the human immunodeficiency virus (HIV)-infected pediatric population in the United States can impact long-term antiretroviral therapy (ART) efficacy. Limited formularies and adherence constraints in children jeopardize lifelong-needed ART. METHODS: We examined treatment failure, drug resistance, and their correlates in ART-naive and ART-experienced children attending the pediatric HIV clinic in Rhode Island between 1991 and 2012. Pol sequences were obtained for phylogenetic, subtype, and resistance analyses. Associations between selected covariates and virologic failure and resistance were evaluated using generalized additive models and Fisher exact tests. RESULTS: Data were available for all 56 clinic-attending children. At diagnosis, 33% were aged <1 year, 31% aged 1-4 years, and 37% aged ≥ 5 years; 54% were male, 73% black or Hispanic, 55% US-born, 20% refugees, and 64% perinatally infected. Of 44 ART-experienced children, 57% had virologic failure, most never virologically suppressed. Failure was associated with missed appointments (P = .05) and missed doses (P < .01). Of 40 children with available genotypes, 35% were infected with non-B subtypes; 6% of ART-naive children had resistance; and 73% of ART-experienced children had ≥ 1 major mutation: (16% conferring triple-class, 47% dual-class, and 37% single-class resistance). An epidemiologically confirmed resistance transmission from a perinatally infected teenage male to a newly infected teenage female was demonstrated. CONCLUSIONS: We report high HIV type 1 diversity, extensive drug resistance among ART-experienced children, and horizontal transmission of resistance in the Rh ode Island pediatric HIV clinic. As HIV-infected children mature into adulthood, close monitoring of ART, adherence, and diagnosis disclosure are essential to optimize patient care.

Transmitted HIV drug resistance at the Thai Red Cross anonymous clinic in Bangkok: results from three consecutive years of annual surveillance.

OBJECTIVES: The aim of this study was to prospectively survey transmitted drug resistance (TDR) among recently infected individuals (mostly MSM). METHODS: TDR was determined in prospective annual cohorts of recently HIV-1-infected individuals consecutively recruited from 2008 to 2010. Resistance interpretation was carried out using Stanford Database tools and the WHO surveillance drug resistance mutation list. Kruskal-Wallis and Fisher's exact tests were used to compare demographic and laboratory outcomes. RESULTS: A total of 299 subjects were enrolled, with 89% MSM. Median viral load was significantly higher in 2010 than in 2008 (P=0.004). Of the 284 analysable reverse transcriptase/protease sequences, TDR to any drug was found in 14/284 (4.9%); 4.0% in 2008, 5.9% in 2009 and 5.3% in 2010, with an increasing trend of TDR to NRTIs and NNRTIs from 2008 to 2010 (P=0.07). Good correlation was found between our data and the WHO threshold surveillance method. Only rilpivirine had significantly higher (P<0.05) predicted resistance in 2010 than in 2008 and 2009. CONCLUSIONS: A trend towards an increase in TDR in Thailand where the major epidemic is among MSM was observed, but did not reach the WHO-defined high-level threshold (>15%). Attention to prevent the development and spread of drug resistance is needed.

Factors Influencing Uptake of Rapid HIV and Hepatitis C Screening Among Drug Misusing Adult Emergency Department Patients: Implications for Future HIV/HCV Screening Interventions.

In this randomized, controlled trial among 957 English- or Spanish-speaking drug misusing adult emergency department (ED) patients, we determined if a tailored brief intervention (BI) increased uptake of rapid HIV/HCV screening, and identified factors associated with greater screening uptake. Rapid HIV/HCV screening uptake was greater in the control than the BI arm (45 vs. 38 %; p < 0.04). Screening uptake depended on elapsed study time and which research staff member offered testing. In the control arm, uptake was lowest for those spending <30 or ≥90 min in the study. In the BI arm, screening uptake generally increased over time. Tailored BI content specifically addressing participant HIV/HCV knowledge, HIV/HCV risk behaviors, or need for HIV/HCV screening was not associated with greater screening uptake. These study findings suggested factors that should be considered when designing future ED-based screening initiatives, such as elapsed study time, who offers testing, and the content of interventions.

Effect of Montelukast vs Placebo on Time to Sustained Recovery in Outpatients with COVID-19: The ACTIV-6 Randomized Clinical Trial.

Importance: The effect of montelukast in reducing symptom duration among outpatients with mild to moderate coronavirus disease 2019 (COVID-19) is uncertain. Objective: To assess the effectiveness of montelukast compared with placebo in treating outpatients with mild to moderate COVID-19. Design Setting and Participants: The ACTIV-6 platform randomized clinical trial aims to evaluate the effectiveness of repurposed medications in treating mild to moderate COVID-19. Between January 27, 2023, and June 23, 2023, 1250 participants ≥30 years of age with confirmed SARS-CoV-2 infection and ≥2 acute COVID-19 symptoms for ≤7 days, were included across 104 US sites to evaluate the use of montelukast. Interventions: Participants were randomized to receive montelukast 10 mg once daily or matched placebo for 14 days. Main Outcomes and Measures: The primary outcome was time to sustained recovery (defined as at least 3 consecutive days without symptoms). Secondary outcomes included time to death; time to hospitalization or death; a composite of hospitalization, urgent care visit, emergency department visit, or death; COVID clinical progression scale; and difference in mean time unwell. Results: Among participants who were randomized and received study drug, the median age was 53 years (IQR 42-62), 60.2% were female, 64.6% identified as Hispanic/Latino, and 56.3% reported ≥2 doses of a SARS-CoV-2 vaccine. Among 628 participants who received montelukast and 622 who received placebo, differences in time to sustained recovery were not observed (adjusted hazard ratio [HR] 1.02; 95% credible interval [CrI] 0.92-1.12; P(efficacy) = 0.63]). Unadjusted median time to sustained recovery was 10 days (95% confidence interval 10-11) in both groups. No deaths were reported and 2 hospitalizations were reported in each group; 36 participants reported healthcare utilization events (a priori defined as death, hospitalization, emergency department/urgent care visit); 18 in the montelukast group compared with 18 in the placebo group (HR 1.01; 95% CrI 0.45-1.84; P(efficacy)=0.48). Five participants experienced serious adverse events (3 with montelukast and 2 with placebo). Conclusions and Relevance: Among outpatients with mild to moderate COVID-19, treatment with montelukast does not reduce duration of COVID-19 symptoms. Trial Registration: ClinicalTrials.gov ( NCT04885530 ).