Polygenic risk, childhood abuse and gene x environment interactions with depression development from middle to late adulthood: A U.S. national life-course study.

OBJECTIVE: Utilizing national longitudinal data, this study examines how polygenic depression risk and childhood abuse interactively influence the life-course development of depressive conditions from middle to late adulthood. METHOD: Data from 7512 participants (4323 females and 3189 males) of European ancestry aged 51-90, retrieved from the U.S. Health and Retirement Study (1992-2020), were analyzed. Childhood physical abuse and polygenic depression score were the primary predictors. Depressive symptoms were assessed using the Center for Epidemiologic Studies-Depression (CESD) scale, and clinical depression risk was a binary indicator. Growth-curve linear mixed and logit mixed-effects models were conducted for analysis. RESULTS: Increasing polygenic depression scores were associated with elevated CES-D levels and potential risks of clinical depression. Males experienced more detrimental effects of childhood abuse on depression development from ages 51 to 90 years. In contract, non-maltreated females generally exhibited higher depressive symptoms and clinical depression risk than males. A significant interactive effect was found between polygenic depression risk and childhood abuse among males. Higher depression levels and clinical risk were observed with increasing polygenic depression score among maltreated males, surpassing those of females with standardized polygenic score ≥0 from age 51 to 90 years. CONCLUSIONS: The interaction between childhood abuse and genetic factors significantly shaped lifelong depression trajectories in males, while the negative impact of abusive parenting remained constant regardless of polygenic depression risk among females. Individualized prevention and intervention strategies could be crucial in mitigating lifelong depression development, especially for high-genetic-risk males with a history of childhood physical abuse.

A Two-stage Approach for Rapid Assessment of the Proportion Achieving Viral Suppression Using Routine Clinical Data.

BACKGROUND: Improving viral suppression among people with HIV reduces morbidity, mortality, and transmission. Accordingly, monitoring the proportion of patients with a suppressed viral load is important to optimizing HIV care and treatment programs. But viral load data are often incomplete in clinical records. We illustrate a two-stage approach to estimate the proportion of treated people with HIV who have a suppressed viral load in the Dominican Republic. METHODS: Routinely collected data on viral load and patient characteristics were recorded in a national database, but 74% of patients on treatment at the time of the study did not have a recent viral load measurement. We recruited a subset of these patients for a rapid assessment that obtained additional viral load measurements. We combined results from the rapid assessment and main database using a two-stage weighting approach and compared results to estimates obtained using standard approaches to account for missing data. RESULTS: Of patients with recent routinely collected viral load data, 60% had a suppressed viral load. Results were similar after applying standard approaches to account for missing data. Using the two-stage approach, we estimated that 77% (95% confidence interval [CI] = 74, 80) of those on treatment had a suppressed viral load. CONCLUSIONS: When assessing the proportion of people on treatment with a suppressed viral load using routinely collected data, applying standard approaches to handle missing data may be inadequate. In these settings, augmenting routinely collected data with data collected through sampling-based approaches could allow more accurate and efficient monitoring of HIV treatment program effectiveness.

Estimating Sizes of Key Populations at the National Level: Considerations for Study Design and Analysis.

BACKGROUND: National estimates of the sizes of key populations, including female sex workers, men who have sex with men, and transgender women are critical to inform national and international responses to the HIV pandemic. However, epidemiologic studies typically provide size estimates for only limited high priority geographic areas. This article illustrates a two-stage approach to obtain a national key population size estimate in the Dominican Republic using available estimates and publicly available contextual information. METHODS: Available estimates of key population size in priority areas were augmented with targeted additional data collection in other areas. To combine information from data collected at each stage, we used statistical methods for handling missing data, including inverse probability weights, multiple imputation, and augmented inverse probability weights. RESULTS: Using the augmented inverse probability weighting approach, which provides some protection against parametric model misspecification, we estimated that 3.7% (95% CI = 2.9, 4.7) of the total population of women in the Dominican Republic between the ages of 15 and 49 years were engaged in sex work, 1.2% (95% CI = 1.1, 1.3) of men aged 15-49 had sex with other men, and 0.19% (95% CI = 0.17, 0.21) of people assigned the male sex at birth were transgender. CONCLUSIONS: Viewing the size estimation of key populations as a missing data problem provides a framework for articulating and evaluating the assumptions necessary to obtain a national size estimate. In addition, this paradigm allows use of methods for missing data familiar to epidemiologists.

Effect of Postnatal HIV Treatment on Clinical Mastitis and Breast Inflammation in HIV-Infected Breast-feeding Women.

BACKGROUND: The relationship between mastitis and antiretroviral therapy among HIV-positive, breast-feeding women is unclear. METHODS: In the Breastfeeding, Antiretrovirals, and Nutrition (BAN) study, conducted in Lilongwe, Malawi, 2369 mother-infant pairs were randomized to a nutritional supplement group and to one of three treatment groups: maternal antiretroviral therapy (ART), infant nevirapine (NVP) or standard of care for 24 weeks of exclusive breast-feeding and 4 weeks of weaning. Among 1472 HIV-infected women who delivered live infants between 2004 and 2007, we estimated cumulative incidence functions and sub-distribution hazard ratios (HR) of mastitis or breast inflammation comparing women in maternal ART (n = 487) or infant nevirapine (n = 492) groups to the standard of care (n = 493). Nutritional supplement groups (743 took, 729 did not) were also compared. RESULTS: Through 28-weeks post-partum, 102 of 1472 women experienced at least one occurrence of mastitis or breast inflammation. The 28-week risk was higher for maternal ART (risk difference (RD) 4.5, 95% confidence interval (CI) 0.9, 8.1) and infant NVP (RD 3.6, 95% CI 0.3, 6.9) compared to standard of care. The hazard of late-appearing mastitis or breast inflammation (from week 5-28) was also higher for maternal ART (HR 6.7, 95% CI 2.0, 22.6) and infant NVP (HR 5.1, 95% CI 1.5, 17. 5) compared to the standard of care. CONCLUSIONS: Mastitis or breast inflammation while breast-feeding is a possible side effect for women taking prophylactic ART and women whose infants take NVP, warranting additional research in the context of postnatal HIV transmission.

Etiology of genital ulcer disease and association with HIV infection in Malawi.

BACKGROUND: The World Health Organization recommends the use of syndromic management for patients presenting with genital ulcer disease (GUD) in developing countries. However, effective treatment guidelines depend on a current country-specific GUD etiological profile, which may change over time. METHODS: From 2004 to 2006, we conducted a cross-sectional analysis of baseline data from patients presenting with GUD at a reference STI clinic in Lilongwe, Malawi. Participants were enrolled in a randomized clinical trial of acyclovir added to syndromic management and followed up for up to 28 days. Serologies for HIV (using parallel rapid tests), herpes simplex virus type 2 (HSV-2; using Focus HerpeSelect IgG2 ELISA [Focus Technologies, Cypress Hill, CA]), and syphilis (rapid plasma reagin confirmed by Treponema pallidum hemagglutination) were determined, with plasma HIV-1 RNA and CD4 count in HIV-positive patients. Genital ulcer disease etiology was determined by real-time multiplex polymerase chain reaction from lesional swabs. RESULTS: A total of 422 patients with GUD (313 men; 74%) were enrolled. Overall seroprevalence of HIV-1, HSV-2, and syphilis were 61%, 72%, and 5%, respectively. Ulcer etiology was available for 398 patients and showed the following: HSV-2, 67%; Haemophilus ducreyi, 15%; T. pallidum, 6%; lymphogranuloma venereum, 6%; mixed infections, 14%, and no etiology, 20%. Most HSV-2 ulcers were recurrent (75%). Among all patients with HSV-2, HIV prevalence was high (67%) and HIV seroprevalence was higher among patients with recurrent HSV-2 compared with patients with first-episode HSV-2 (78% vs. 39%, P < 0.001). CONCLUSIONS: Herpes simplex virus type 2 ulcers are highly prevalent in this symptomatic population and strongly associated with HIV. Unlike most locations in sub-Saharan Africa, H. ducreyi remains prevalent in this population and requires periodic monitoring and an appropriate treatment regimen.

North Carolina public school teachers' contact patterns and mask use within and outside of school during the prevaccine phase of the COVID-19 pandemic.

BACKGROUND: Teachers are central to school-associated transmission networks, but little is known about their behavioral patterns during the COVID-19 pandemic. METHODS: We conducted a cross-sectional survey of 700 North Carolina public school teachers in 4 districts open to in-person learning in November-December 2020 (pre-COVID-19 vaccines). We assessed indoor and outdoor time spent, numbers of people encountered at <6 feet ("close contacts"), and mask use by teachers and those around them at specific locations on the most recent weekday and weekend day. RESULTS: Nearly all respondents reported indoor time at home (98%) and school (94%) on the most recent weekday, while 62% reported indoor time at stores, 18% at someone else's home, and 17% at bars/restaurants. Responses were similar for the most recent weekend day, excepting school (where 5% reported indoor time). Most teachers (>94%) reported wearing masks inside school, stores, and salons; intermediate percentages (∼50%-85%) inside places of worship, bars/restaurants, and recreational settings; and few (<25%) in their or others' homes. Approximately half reported daily close contact with students. CONCLUSIONS: As schools reopened in the COVID-19 pandemic, potential transmission opportunities arose through close contacts within and outside of school, along with suboptimal mask use by teachers and/or those around them. Our granular estimates underscore the importance of multilayered mitigation strategies and can inform interventions and mathematical models addressing school-associated transmission.

Incidence and Secondary Transmission of SARS-CoV-2 Infections in Schools.

BACKGROUND: In an effort to mitigate the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), North Carolina closed prekindergarten through grade 12 public schools to in-person instruction on March 14, 2020. On July 15, 2020, North Carolina's governor announced schools could open via remote learning or a hybrid model that combined in-person and remote instruction. In August 2020, 56 of 115 North Carolina school districts joined The ABC Science Collaborative (ABCs) to implement public health measures to prevent SARS-CoV-2 transmission and share lessons learned. We describe secondary transmission of SARS-CoV-2 within participating school districts during the first 9 weeks of in-person instruction in the 2020-2021 academic year. METHODS: From August 15, 2020 to October 23, 2020, 11 of 56 school districts participating in ABCs were open for in-person instruction for all 9 weeks of the first quarter and agreed to track incidence and secondary transmission of SARS-CoV-2. Local health department staff adjudicated secondary transmission. Superintendents met weekly with ABCs faculty to share lessons learned and develop prevention methods. RESULTS: Over 9 weeks, 11 participating school districts had >90 000 students and staff attend school in person. Among these students and staff, 773 community-acquired SARS-CoV-2 infections were documented by molecular testing. Through contact tracing, health department staff determined an additional 32 infections were acquired within schools. No instances of child-to-adult transmission of SARS-CoV-2 were reported within schools. CONCLUSIONS: In the first 9 weeks of in-person instruction in North Carolina schools, we found extremely limited within-school secondary transmission of SARS-CoV-2, as determined by contact tracing.

Opportunities for Enhanced Strategic Use of Surveys, Medical Records, and Program Data for HIV Surveillance of Key Populations: Scoping Review.

BACKGROUND: Normative guidelines from the World Health Organization recommend tracking strategic information indicators among key populations. Monitoring progress in the global response to the HIV epidemic uses indicators put forward by the Joint United Nations Programme on HIV/AIDS. These include the 90-90-90 targets that require a realignment of surveillance data, routinely collected program data, and medical record data, which historically have developed separately. OBJECTIVE: The aim of this study was to describe current challenges for monitoring HIV-related strategic information indicators among key populations ((men who have sex with men [MSM], people in prisons and other closed settings, people who inject drugs, sex workers, and transgender people) and identify future opportunities to enhance the use of surveillance data, programmatic data, and medical record data to describe the HIV epidemic among key populations and measure the coverage of HIV prevention, care, and treatment programs. METHODS: To provide a historical perspective, we completed a scoping review of the expansion of HIV surveillance among key populations over the past three decades. To describe current efforts, we conducted a review of the literature to identify published examples of SI indicator estimates among key populations. To describe anticipated challenges and future opportunities to improve measurement of strategic information indicators, particularly from routine program and health data, we consulted participants of the Third Global HIV Surveillance Meeting in Bangkok, where the 2015 World Health Organization strategic information guidelines were launched. RESULTS: There remains suboptimal alignment of surveillance and programmatic data, as well as routinely collected medical records to facilitate the reporting of the 90-90-90 indicators for HIV among key populations. Studies (n=3) with estimates of all three 90-90-90 indicators rely on cross-sectional survey data. Programmatic data and medical record data continue to be insufficiently robust to provide estimates of the 90-90-90 targets for key populations. CONCLUSIONS: Current reliance on more active data collection processes, including key population-specific surveys, remains warranted until the quality and validity of passively collected routine program and medical record data for key populations is optimized.

Reflux Incidence among Exclusively Breast Milk Fed Infants: Differences of Feeding at Breast versus Pumped Milk.

The practice of feeding infants expressed breast milk is increasing in the United States, but the impacts on infant and maternal health are still understudied. This study examines the monthly incidence of regurgitation (gastro-esophageal reflux) in exclusively breast milk fed infants from ages two to six months. Among infants whose mothers participated in the Infant Feeding Practices II Study (IFPS II; 2005-2007), data on reflux and feeding mode were collected by monthly questionnaires. A longitudinal, repeated measures analysis was used, with feeding mode lagged by one month in order to compare reflux incidence among infants fed directly at the breast to infants receiving pumped breast milk. Mothers in both feeding groups had similar characteristics, although a greater proportion feeding at least some pumped milk were primiparous. The number of exclusively breastfed infants decreased steadily between months 2 and 6, although the proportion fed at the breast remained similar over time. An association between feeding mode and reflux incidence was not found; however, the analyses were limited by a small number of reported reflux cases. More studies are needed to further explain the relationship between different feeding modes and infant reflux.

Prevention and control of sexually transmissible infections among hotel-based female sex workers in Dhaka, Bangladesh.

BACKGROUND: Hotel-based sex workers in Bangladesh have high rates of sexually transmissible infections (STIs), high client turnover and low condom use. Two monthly clinic-based strategies were compared: periodic presumptive treatment (PPT) and enhanced syndromic management (ESM) - one round of presumptive treatment followed by treatment based on assessment and laboratory tests. METHODS: A randomised controlled trial compared PPT and ESM by prevalence and incidence, behaviour, retention, cost and STI incidence and prevalence. Demographic, behavioural and clinical data were collected from women at two clinics in Dhaka. All women received presumptive treatment and were randomised to receive PPT or ESM at nine monthly visits. RESULTS: In total, 549 women (median age: <20 years) were enrolled. At baseline, the prevalence of chlamydia (Chlamydia trachomatis) and gonorrhoea (Neisseria gonorrhoeae) was 41% (ESM: 41%; PPT: 42%). After 9 months, chlamydia and gonorrhoea decreased to 7% overall, (ESM: 7.4%; PPT: 6.8%). At each visit, 98% of women receiving ESM met the therapy criteria and were treated. Retention was low (50%). Total costs were 50% lower per visit for each woman for PPT (ESM: $11.62 v. PPT: $5.80). The number of sex work sessions was reduced from 3.3 to 2.5 (P<0.001), but income did not change. Coercion was reduced but condom use at last sex did not change significantly. CONCLUSIONS: Monthly PPT and ESM were effective approaches for STI control. PPT offered a feasible, low-cost alternative to ESM. Educational aspects led to a reduction in coercion and fewer sessions. Implementation studies are needed to improve condom use and retention.