HIV and viremia prevalence in non-migrating members of migrant households in Rakai region, Uganda: A cross-sectional population-based study.

Introduction: In sub-Saharan Africa, migrants are more likely to be HIV seropositive and viremic than non-migrants. However, little is known about HIV prevalence and viremia in non-migrants living in households with in- or out-migration events. We compared HIV outcomes in non-migrating persons in households with and without migration events using data from the Rakai Community Cohort Study (RCCS), an open population-based cohort in Uganda. Methods: We analyzed RCCS survey data from one survey round collected between August 2016 and May 2018 from non-migrating participants aged 15-49. Migrant households were classified as those reporting ≥1 member moving into or out of the household since the prior survey. A validated rapid test algorithm determined HIV serostatus. HIV viremia was defined as >1,000 copies/mL. Modified Poisson regression was used to estimate associations between household migration and HIV outcomes, with results reported as adjusted prevalence ratios (adjPR) with 95% confidence intervals (95%CI). Analyses were stratified by gender, direction of migration (into/out of the household), and relationship between non-migrants and migrants (e.g., spouse). Results: There were 14,599 non-migrants (7,654, 52% women) identified in 9,299 households. 4,415 (30%) lived in a household with ≥1 recent migrant; of these, 972(22%) had migrant spouses, 1,102(25%) migrant children, and 875(20%) migrant siblings. Overall, HIV prevalence and viremia did not differ between non-migrants in migrant and non-migrant households. However, in stratified analyses, non-migrant women with migrant spouses were significantly more likely to be HIV seropositive compared to non-migrant women with non-migrant spouses (adjPR:1.44, 95%CI:1.21-1.71). Conversely, non-migrant mothers living with HIV who had migrant children were less likely to be viremic (adjPR:0.34, 95%CI:0.13-0.86). Among non-migrant men living with HIV, spousal migration was associated with a non-significant increased risk of viremia (adjPR:1.37, 95%CI:0.94-1.99). Associations did not typically differ for migration into or out of the household. Conclusions: Household migration was associated with HIV outcomes for certain non-migrants, suggesting that the context of household migration influences the observed association with HIV outcomes. In particular, non-migrating women with migrating spouses were more likely to have substantially higher HIV burden. Non-migrants with migrant spouses may benefit from additional support when accessing HIV services.

Impact of malnutrition on the outcome and length of hospital stay in elective pediatric surgical patients: prospective cohort study at tertiary hospitals in Ethiopia.

BACKGROUND: Pediatric surgical patients in low and middle-income countries suffer from malnutrition on top of the surgical pathology and post-operative stress which increases post-operative morbidity and mortality. Malnutrition is highly prevalent in Africa and is expected to impact the outcome of surgical patients. The study was aimed at determining the impact of malnutrition on the outcome and length of hospital stay in elective pediatric surgical patients. METHODS: A prospective study was done on children, aged one month to fourteen years, who had undergone elective general surgery. Upon admission, nutritional assessment using an anthropometric indicator was undertaken and used to derive the WHO Anthro Z scores. Malnutrition was defined as a binary outcome: severely/moderately malnourished (Z < -2) versus well nourished (Z ≥ -2). After surgery, postoperative complications were documented. Chi-squared tests and t-tests were used to assess associations. RESULTS: Of the 109 enrolled children, 49 (45%) had malnutrition preoperatively. Infants had a higher prevalence of malnutrition (65% versus 35%, p-value = 0·028) compared to older children. Postoperative infection was relatively more common in malnourished children (27·1% versus 20%). The mean post-operative stays were 5·69 days (SD 0.46) for well-nourished children and 6.89 days (SD 0·9) for malnourished patients but the difference was not statistically significant. CONCLUSION: We observed neither significant long hospital stays nor a higher incidence of postoperative infection among children with malnutrition. Further investigations with a larger sample size are warranted.

A trial of nurturing care among children who are HIV-exposed and uninfected in eSwatini.

INTRODUCTION: Children who are HIV-exposed and uninfected (CHEU) are a growing population at potential risk of poor neurocognitive development. We tested a nurturing care intervention on children's neurocognitive development and maternal depressive symptoms (primary) with mediation through caregiving activities (secondary). METHODS: This study was conducted among six intervention and nine comparison antenatal-care/prevention of vertical transmission (ANC/PVT) HIV clinics in eSwatini. We enrolled pregnant women and measured infant development at 9 and 18 months. mothers2mothers (m2m) designed and implemented the clinic-home-community-based intervention. We measured infants' neurodevelopment, maternal depressive symptoms and caregiving activities with the Mullen Scales of Early Learning (MSEL), Edinburgh Postnatal Depression Scale, HOME Inventory and Family Care Indicators. We fitted linear mixed effects regression models with clinic random effects to compare intervention versus comparison arms, and generalised structural equation models to evaluate mediation, adjusting for confounders. RESULTS: Mother-infant pairs (n = 429) participated between January 2016 through May 2018. Socio-demographic characteristics were balanced between arms except for higher rates of peri-urban versus rural residence and single versus married mothers in the comparison group. The 18 month retention was 82% (180/220) intervention, 79% (166/209) comparison arm, with 25 infant deaths. Intervention MSEL scores were significantly, and modestly, higher in receptive language (55.7 [95% CI 54.6, 56.9] vs. 53.7 [95% CI 52.6, 54.8]), expressive language (42.5 [95% CI 41.6, 39.8] vs. 40.8 [95% CI 39.8, 41.7]) and composite MSEL (85.4 [95% CI 83.7, 84.5] vs. 82.7 [95% CI 81.0, 84.5]), with no difference in maternal depressive symptoms or in observations of mother-child interactions. Intervention book-sharing scores were higher (0.63 vs. 0.41) and mediated the effect on MSEL scores (indirect effect, p-values ≤ 0.024). The direct effects on visual reception and expressive language scores were significantly higher in the intervention compared to the comparison arm (coefficients 1.93 [95% CI 0.26, 3.60] and 1.66 [95% CI 0.51, 2.79, respectively]). CONCLUSIONS: Nurturing care interventions can be integrated into ANC/PVT clinic-home-community programmes. The intervention, mediated through interactive caregiving activities, increased language development scores among CHEU. Partnering with a local team, m2m, to design and implement a culturally relevant intervention illustrates the ability to impact parent-child play and learning activities that are associated with children's neurodevelopment.

Brief Report: Changing Characteristics Among In-Hospital HIV Deaths: An 11-Year Retrospective Review of a Regional Hospital in South Africa.

BACKGROUND: Elevated HIV-associated mortality persists, despite a notable decline with the expansion of antiretroviral therapy (ART). In South Africa, the relative majority of deaths occur in health facilities, providing an opportunity to track decedent characteristics. SETTING: We analyzed data from 14,870 adult patients who died between 2008 and 2018 at Klerksdorp/Tshepong Hospital Complex in South Africa. METHODS: Recorded data included demographics, causes of death, HIV status, ART, and tuberculosis (TB) history. We present summary statistics and results from linear, log-binomial, and multinomial regressions to quantify changes over time. RESULTS: Over the study period, the median age of decedents with HIV in the hospital increased from 39.3 to 43.4 years, and there was a switch to male predominance (46%-54%). Those who died at a younger age (<40 years) remained more likely to be HIV-positive than the older age group, despite the overall proportion of HIV-positivity decreasing over time. The proportion of decedents with HIV ever started on ART increased from 21% to 67%. The proportion of HIV patients dying from TB and AIDS-defining illnesses decreased from 31% to 22%. CONCLUSIONS: We noted a shift in deaths over time to more men and older individuals, whereas the burden of HIV was heaviest on the younger age groups. Advanced HIV disease remained an important cause of mortality. We also observed an increase in less-traditional opportunistic illnesses among those with HIV, including malignancy, cardiovascular disease, and kidney disease. The high proportion of patients on ART who died prematurely requires further research and interventions.

Investigating linkage to care between hospitals and primary care clinics for people with TB in rural South Africa.

People with tuberculosis (TB) are often lost to follow-up during treatment transition to another facility. These losses may result in substantial morbidity and mortality but are rarely recorded. We conducted a record review on adults diagnosed with TB at 11 hospitals in Limpopo, South Africa, who were subsequently transferred to a local clinic to initiate or continue treatment. We then performed in-depth record reviews at the primary care clinic to which they were referred and called participants who could not be identified as starting treatment. Between August 2017 and April 2018, we reviewed records of 778 individuals diagnosed with TB in-hospital and later referred to local clinics for treatment. Of the 778, 88 (11%) did not link to care, and an additional 43 (5.5%) died. Compared to people without cough, those with cough had higher odds of linking to care (aOR = 2.01, 95% CI: 1.26-3.25, p = 0.005) and were also linked more quickly [adjusted Time Ratio (aTR) = 0.53, 95% CI:0.36-0.79, p<0.001], as were those diagnosed microbiologically (aOR = 1.86, 95% CI: 1.16-3.06, p = 0.012; aTR = 0.58, 95% CI: 0.34-0.98, p = 0.04). People diagnosed with TB in hospitals often disengage following referral to local clinics. Interventions to identify and re-engage people who do not present to local clinics within days of referral might close an important gap in the TB treatment cascade.

Pragmatic cluster-randomized trial of home-based preventive treatment for TB in Ethiopia and South Africa (CHIP-TB).

BACKGROUND: Each year, 1 million children develop TB resulting in over 200,000 child deaths. TB preventive treatment (TPT) is highly effective in preventing TB but remains poorly implemented for household child contacts. Home-based child contact management and TPT services may improve access to care. In this study, we aim to evaluate the effectiveness and cost-effectiveness of home-based contact management with TPT initiation in two TB high-burden African countries, Ethiopia and South Africa. METHODS: This pragmatic cluster randomized trial compares home-based versus facility-based care delivery models for contact management. Thirty-six clinics with decentralized TB services (18 in Ethiopia and 18 in South Africa) were randomized in a 1:1 ratio to conduct either home-based or facility-based contact management. The study will attempt to enroll all eligible close child contacts of infectious drug-sensitive TB index patients diagnosed and treated for TB by one of the study clinics. Child TB contact management, including contact tracing, child evaluation, and TPT initiation and follow-up, will take place in the child's home for the intervention arm and at the clinic for the control arm. The primary outcome is the cluster-level ratio of the number of household child contacts less than 15 years of age in Ethiopia and less than 5 years of age in South Africa initiated on TPT per index patient, comparing the intervention to the control arm. Secondary outcomes include child contact identification and the TB prevention continuum of care. Other implementation outcomes include acceptability, feasibility, fidelity, cost, and cost-effectiveness of the intervention. DISCUSSION: This implementation research trial will determine whether home-based contact management identifies and initiates more household child contacts on TPT than facility-based contact management. TRIAL REGISTRATION: NCT04369326 . Registered on April 30, 2020.

Evaluating systematic targeted universal testing for tuberculosis in primary care clinics of South Africa: A cluster-randomized trial (The TUTT Trial).

BACKGROUND: The World Health Organization (WHO) recommends systematic symptom screening for tuberculosis (TB). However, TB prevalence surveys suggest that this strategy does not identify millions of TB patients, globally. Undiagnosed or delayed diagnosis of TB contribute to TB transmission and exacerbate morbidity and mortality. We conducted a cluster-randomized trial of large urban and rural primary healthcare clinics in 3 provinces of South Africa to evaluate whether a novel intervention of targeted universal testing for TB (TUTT) in high-risk groups diagnosed more patients with TB per month compared to current standard of care (SoC) symptom-directed TB testing. METHODS AND FINDINGS: Sixty-two clinics were randomized; with initiation of the intervention clinics over 6 months from March 2019. The study was prematurely stopped in March 2020 due to clinics restricting access to patients, and then a week later due to the Coronavirus Disease 2019 (COVID-19) national lockdown; by then, we had accrued a similar number of TB diagnoses to that of the power estimates and permanently stopped the trial. In intervention clinics, attendees living with HIV, those self-reporting a recent close contact with TB, or a prior episode of TB were all offered a sputum test for TB, irrespective of whether they reported symptoms of TB. We analyzed data abstracted from the national public sector laboratory database using Poisson regression models and compared the mean number of TB patients diagnosed per clinic per month between the study arms. Intervention clinics diagnosed 6,777 patients with TB, 20.7 patients with TB per clinic month (95% CI 16.7, 24.8) versus 6,750, 18.8 patients with TB per clinic month (95% CI 15.3, 22.2) in control clinics during study months. A direct comparison, adjusting for province and clinic TB case volume strata, did not show a significant difference in the number of TB cases between the 2 arms, incidence rate ratio (IRR) 1.14 (95% CI 0.94, 1.38, p = 0.46). However, prespecified difference-in-differences analyses showed that while the rate of TB diagnoses in control clinics decreased over time, intervention clinics had a 17% relative increase in TB patients diagnosed per month compared to the prior year, interaction IRR 1.17 (95% CI 1.14, 1.19, p < 0.001). Trial limitations were the premature stop due to COVID-19 lockdowns and the absence of between-arm comparisons of initiation and outcomes of TB treatment in those diagnosed with TB. CONCLUSIONS: Our trial suggests that the implementation of TUTT in these 3 groups at extreme risk of TB identified more TB patients than SoC and could assist in reducing undiagnosed TB patients in settings of high TB prevalence. TRIAL REGISTRATION: South African National Clinical Trials Registry DOH-27-092021-4901.

Leveraging mHealth and Patient Supporters for African Americans' and Latinxs' Engagement in HIV Care (LEAN): Protocol for a Randomized, Controlled, Effectiveness-Implementation Trial.

BACKGROUND: Despite substantial investments in ending the HIV epidemic, disparities in HIV care persist, and there is an urgent need to evaluate novel and scalable approaches to improving HIV care engagement and viral suppression in real-world settings. OBJECTIVE: This paper aims to describe a study protocol for a pragmatic type II hybrid effectiveness-implementation randomized controlled trial comparing existing standard of care clinic HIV linkage, adherence, and retention (LAR) protocols to a mobile health (mHealth)-enhanced linkage, adherence, and retention (mLAR) intervention. METHODS: The study will enroll 450 participants from clinics in Baltimore City. Eligibility criteria include being ≥18 years of age, having a new HIV diagnosis or being HIV-positive and out of care, or being HIV-positive and deemed by clinic staff as someone who could benefit from linkage and retention services. Participants randomized to the intervention receive mHealth-supported patient navigation for 12 months. Participants in the control group receive the referring clinic's standard of care patient support. The primary outcome is HIV virologic suppression at 12 months. A subset of participants will be interviewed at 12 months to learn about their HIV care experiences and, for those in the intervention arm, their experiences with the mLAR intervention. This protocol was developed in collaboration with the Baltimore City Health Department (BCHD) and the Maryland Department of Health (MDH) and with input from a community advisory board. RESULTS: Enrollment began on February 25, 2020. As of August 11, 2022, 411 of the 450 target participants had been enrolled. CONCLUSIONS: Pragmatic implementation science trials designed with input from key stakeholders, including health departments and community members, can help evaluate the evidence for mHealth interventions to reduce HIV health disparities. TRIAL REGISTRATION: ClinicalTrials.gov NCT03934437; https://clinicaltrials.gov/ct2/show/NCT03934437. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/42691.

Addressing the unmet mental health needs of people living with HIV: a scoping review of interventions in sub-Saharan Africa.

Some mental health interventions have addressed mental health among people living with HIV (PLWH) using a variety of approaches, but little is known about the details of such interventions in sub-Saharan Africa (SSA), a region that bears the largest burden of HIV in the world. The present study describes mental health interventions for PLWH in SSA regardless of the date and language of publication. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews (PRISMA-ScR) reporting guidelines, we identified 54 peer-reviewed articles on interventions addressing adverse mental health conditions among PLWH in SSA. The studies were conducted in 11 different countries, with the highest number of studies in South Africa (33.3%), Uganda (18.5%), Kenya (9.26%), and Nigeria (7.41%). While only one study was conducted before the year 2000, there was a gradual increase in the number of studies in the subsequent years. The studies were mostly conducted in hospital settings (55.5%), were non-pharmacologic (88.9%), and interventions were mostly cognitive behavioural therapy (CBT) and counselling. Task shifting was the primary implementation strategy used in four studies. Interventions addressing the mental health needs of PLWH that incorporates the unique challenges and opportunities in SSA is highly recommended.

Yield of Facility-based Targeted Universal Testing for Tuberculosis With Xpert and Mycobacterial Culture in High-Risk Groups Attending Primary Care Facilities in South Africa.

BACKGROUND: We report the yield of targeted universal tuberculosis (TB) testing of clinic attendees in high-risk groups. METHODS: Clinic attendees in primary healthcare facilities in South Africa with one of the following risk factors underwent sputum testing for TB: human immunodeficiency virus (HIV), contact with a TB patient in the past year, and having had TB in the past 2 years. A single sample was collected for Xpert-Ultra (Xpert) and culture. We report the proportion positive for Mycobacterium tuberculosis. Data were analyzed descriptively. The unadjusted clinical and demographic factors' relative risk of TB detected by culture or Xpert were calculated and concordance between Xpert and culture is described. RESULTS: A total of 30 513 participants had a TB test result. Median age was 39 years, and 11 553 (38%) were men. The majority (n = 21734, 71%) had HIV, 12 492 (41%) reported close contact with a TB patient, and 1573 (5%) reported prior TB. Overall, 8.3% were positive for M. tuberculosis by culture and/or Xpert compared with 6.0% with trace-positive results excluded. In asymptomatic participants, the yield was 6.7% and 10.1% in symptomatic participants (with trace-positives excluded). Only 10% of trace-positive results were culture-positive. We found that 55% of clinic attendees with a sputum result positive for M. tuberculosis did not have a positive TB symptom screen. CONCLUSIONS: A high proportion of clinic attendees with specific risk factors (HIV, close TB contact, history of TB) test positive for M. tuberculosis when universal testing is implemented.

Household- Versus Incentive-Based Contact Investigation for Tuberculosis in Rural South Africa: A Cluster-Randomized Trial.

BACKGROUND: Household contact investigation for people newly diagnosed with tuberculosis (TB) is poorly implemented, particularly in low- and middle-income countries. Conditional cash incentives may improve uptake. METHODS: We conducted a pragmatic, cluster-randomized, crossover trial of 2 TB contact investigation approaches (household-based and incentive-based) in 28 public primary care clinics in South Africa. Each clinic used 1 approach for 18 months, followed by a 6-month washout period, after which the opposite approach was used. Fourteen clinics were randomized to each approach. In the household-based arm, we conducted TB screening and testing of contacts at the household. In the incentive-based arm, both index patients and ≤10 of their close contacts (either within or outside the household) were given small cash incentives for presenting to study clinics for TB screening. The primary outcome was the number of people with incident TB who were diagnosed and started on treatment at study clinics. RESULTS: From July 2016 to January 2020, we randomized 28 clinics to each study arm, and enrolled 782 index TB patients and 1882 contacts in the household-based arm and 780 index patients and 1940 contacts in the incentive-based arm. A total of 1413 individuals started on TB treatment in the household-based arm and 1510 in the incentive-based arm. The adjusted incidence rate ratio of TB treatment initiation in the incentive- versus household-based arms was 1.05 (95% confidence interval: .97-1.13). CONCLUSIONS: Incentive-based contact investigation for TB has similar effectiveness to traditional household-based approaches and may be a viable alternative or complementary approach to household-based investigation.

Arrhythmogenic Right Ventricular Cardiomyopathy Prevalence and Arrhythmic Outcomes in At-Risk Family Members: A Systematic Review and Meta-Analysis.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a complex cardiomyopathy with autosomal dominant inheritance and age-related incomplete penetrance, characterized by a high risk of sudden cardiac death. Recent professional consensus guidelines recommend clinical cardiac lifelong serial screening for at-risk family members refined only by age, but family genotype might influence necessary screening. Although numerous studies report prevalence of disease and arrhythmia in family members and explore predictors of penetrance and arrhythmic risk, a systematic review consolidating this evidence is lacking. METHODS: We searched Medline (PubMed), Embase, The Cochrane Library, and Web of Science for studies that reported prevalence of (1) diagnosis of ARVC per 2010 Task Force Criteria and/or (2) sustained ventricular arrhythmias (VA) in at least 10 family members of definite patients with ARVC. RESULTS: We identified 41 studies, including 36 that reported diagnosis by Task Force Criteria and 22 VA. Meta-analysis of 1359 family members, from 13 unique cohorts showed an average prevalence estimate of 25% for diagnosis as per Task Force Criteria (95% CI, 0.15-0.35, I2=96.44%). Overall prevalence of VA among gene-positive family members was 18% (95% CI, 0.13-0.23, I2=33.25%) in 7 independent studies (n=597). Family genotype was a significant risk factor for diagnosis of both ARVC (odds ratio, 6.91 [95% CI, 1.27-37.70]; P=0.0005) and VA (odds ratio, 13.62 [95% CI, 0.91-204.13]; P=0.06). Male gender was not associated with disease prevalence (odds ratio, 1.18 [95% CI, 0.72-1.95]; P=0.42) or VA (odds ratio, 0.81 [95% CI, 0.51-1.29]; P=0.91). CONCLUSIONS: The prevalence of ARVC and VA in at-risk family members differs significantly based on family genotype. Although recent recommendations provide a guideline based only on age, we propose screening every 1 to 2 years for gene-positive family members and every 3 to 5 years for first-degree relatives of gene-elusive cases, as long as they are asymptomatic and not athletes.

Conditional Cash Transfers to Incentivize Tuberculosis Screening: Description of a Novel Strategy for Contact Investigation in Rural South Africa.

BACKGROUND: Providing incentives to screen close contacts for tuberculosis (TB) is an alternative to household-based contact investigation. We aimed to characterize patients and contexts where this incentive-based strategy might be preferred. METHODS: This is a secondary analysis of a cluster randomized trial of TB contact investigation in Limpopo District, South Africa, conducted between 2016 and 2020. Twenty-eight clinics were randomly allocated to household-based vs incentive-based contact investigation. In the incentive-based arm, index participants and contacts received transport reimbursement and incentives for TB screening and microbiological diagnosis of contacts. We estimated differences in mean number of contacts per index participant with household-based vs incentive-based contact investigation overall and within subgroups of index participants. RESULTS: A total of 3776 contacts (1903 in the incentive-based and 1873 in the household-based arm) were referred by 2501 index participants. A higher proportion of contacts in the incentive-based than household-based arm were adults (72% vs 59%), reported chronic TB symptoms (25% vs 16%) or ever smoking (23% vs 11%). Index participants who walked or bicycled to a clinic referred 1.03 more contacts per index (95% confidence interval [CI], .48 to 1.57) through incentive-based than household-based investigation. Index participants living with >5 household members referred 0.48 more contacts per index (95% CI, .03 to .94) through household-based than incentive-based investigation. CONCLUSIONS: Relative to household-based investigation, incentive-based investigation identifies contacts likely at higher risk for active TB. Incentive-based investigation may be more appropriate for index participants who can easily access clinics, versus household-based investigation for patients with large households. Clinical Trials Registration. NCT02808507.

Racial differences in the dermatological manifestations of tuberous sclerosis complex and the potential effects on diagnosis and care.

Background: Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disorder of non-malignant tumor growths throughout major organ systems and neurological, neuropsychiatric, renal, and pulmonary co-morbidities. Skin manifestations are readily visible, often develop early in life, and are major features that contribute to TSC diagnosis. Medical photographs of such manifestations are commonly shown as examples from White individuals creating a potential barrier to accurately identifying these features in darker skinned individuals. Objectives: The aim of this report is to raise awareness of dermatological manifestations associated with TSC, compare their appearance by race, and consider how recognition of these features could impact diagnosis and treatment of TSC. Design and Methods: We conducted a retrospective chart review at the TSC Center of Excellence (TSCOE) at the Kennedy Krieger Institute, which included all patients in the center from 2009 (inception) through the end of the calendar year 2015 and analyzed data from the TSC Alliance Natural History Database (NHD). Results: Among TSCOE patients, 50% of Black patients were diagnosed before the age of 1 year, compared with 70% of White patients. NHD data corroborated this trend showing a significant difference with only 38% of Blacks as compared with 50% of Whites were diagnosed at age ⩽1 year. A significant difference was observed where White participants had higher odds of having received genetic testing in both data sets. While no differences in the total number of TSC features was observed in either data set, shagreen patches and cephalic fibrous plaques were more frequently recorded in the NHD for Black individuals. Conclusion: We highlight a disparity in the representation of Black participants within the NHD, TSCOE, and TSC trials, in addition to differences in utilization of molecular testing and topical mechanistic target of rapamycin (mTOR) inhibitor therapy between Black and White individuals. We show a trend toward later diagnosis age in Black individuals. These differences between races warrant further study across additional clinical sites and other minority groups.

Differences in skin manifestations between races in individuals with tuberous sclerosis complex and the potential effects of these differences on diagnosis and care Background: To our knowledge, tuberous sclerosis complex (TSC) does not affect races at different frequencies; however, observations in clinical settings anecdotally, and results from research studies, suggest a disparity in the representation and diagnosis of Black individuals with TSC. Historically, it has been noted that TSC facial features, such as angiofibromas, present differently in individuals with darker skin tones and are often misdiagnosed leading to delays in TSC diagnosis and treatment. Objectives: The aim of this publication is to identify differences in TSC skin features between Black and White individuals to raise awareness in the clinics and community. In addition, we provide insight into how these differences can affect the timing of TSC diagnosis and subsequent treatment regimens. We aim to highlight these potential disparities to ensure improved timing in diagnosis and treatment regimens for all affected by TSC in the future. Design and Methods: Differences between Black and White individuals with TSC were observed looking at historical medical data collected at a TSC Center of Excellence (TSCOE) on all patients seen in the center from 2009 through the end of 2015 and in the TSC Alliance Natural History Database (NHD) that has been collecting clinical data on individuals with TSC since 2006. Results: We observed that Black individuals are less likely to be diagnosed at ⩽1 year of age as compared with White individuals within the NHD. Data from the TSCOE support these findings but were not statistically significant. We observed a difference in NHD participation with only 150 Black individuals participating, representing 6% of total NHD participants. Our data indicate a difference between Black and White individuals both in the TSCOE and NHD showing that Black individuals are less likely to receive genetic testing, utilize topical mTOR therapy, and participate in TSC clinical trials. Conclusion: Given the observed trends, outreach and education to clinicians and other healthcare providers is needed to inform of these differences. Given that skin manifestations play an essential role in early recognition of TSC and timely referral to TSC specialists, we hope these data lead to improvement in the recognition of TSC in darker skinned individuals at earlier ages, thus improving clinical outcomes associated with TSC manifestations by optimizing treatment early in life.

High occurrence of witnessing an opioid overdose in a sample of women who use heroin in Tanzania: Implications for overdose prevention.

BACKGROUND: Opioid overdose is preventable and reversible. To target overdose prevention training and naloxone distribution, it is important to understand characteristics of those people who use drugs most likely to witness an overdose. In this paper we report the proportion and characteristics of women who use heroin that have witnessed an opioid overdose in Dar es Salaam, Tanzania. METHODS: We conducted a cross-sectional survey with 200 women who use heroin. We fitted unadjusted and adjusted logistic regression models with witnessing an opioid overdose as the dependent variable and sociodemographic and drug use-related variables as independent variables. RESULTS: The majority of participants (85%) reported having ever witnessed an opioid overdose. Age (adjusted Odds Ratio [aOR] = 1.09; 95% CI: 1.02-1.12), having ever attempted to stop heroin use (aOR = 11.27; 95% CI: 2.25-56.46), history of arrest (aOR = 3.75; 95% CI: 1.32-10.63), and spending time daily in places where people use drugs (aOR = 3.72; 95% CI: 1.43-9.64) were found to be independently associated with ever witnessing an overdose. CONCLUSIONS: Findings suggest the need for expanded access to naloxone to lay people and community and peer-based overdose prevention training in Tanzania, including the distribution of naloxone in settings with high drug use.

Correlates of Non-fatal, Opioid Overdose among Women Who Use Opioids in Dar es Salaam, Tanzania.

BACKGROUND: As opioid overdoses and deaths increase globally, little is known about these dimensions in Sub-Saharan Africa. In this paper, we explore factors associated with opioid overdose experiences among a sample of women who use opioids in Dar es Salaam, Tanzania. METHODS: We conducted a cross-sectional survey with 200 women who use opioids in Dar es Salaam, Tanzania, recruited via respondent-driven sampling. We fitted unadjusted and adjusted log-binomial regression models with robust standard errors to examine associations between participant characteristics and reporting ever had an opioid overdose in terms of prevalence ratios. RESULTS: Thirty-four percent (n = 68) of participants reported having ever had an opioid overdose. In the final adjusted model, having ever attempted to stop using heroin (adj. PR = 1.46, 95% CI: 1.01-2.12), sleeping outside in the past 6 months (adj. PR = 1.93, 95% CI: 1.29-2.91), injecting drugs (adj. PR = 1.78, 95% CI: 1.19-2.66), alcohol use (adj. PR = 1.56, 95% CI: 1.09-2.23), and having moderately severe to severe depression (adj. PR = 3.10, 95% CI: 1.07-8.97) were all found to be significantly associated with having ever had an opioid overdose. CONCLUSIONS: We demonstrate factors associated with opioid overdose among women who use drugs in Tanzania that may not be addressed with injection-focused harm reduction efforts. Our findings suggest the need for overdose surveillance efforts and further work to characterize overdose risks in this context in order to design relevant, targeted interventions to prevent opioid overdose in sub-Saharan Africa.

Relationship of circulating immune cells with lifestyle factors and cancer recurrence in early-stage breast cancer.

PURPOSE: To evaluate the relationship of circulating immune cells with recurrence and metabolic/lifestyle factors in patients with early-stage breast cancer. METHODS: Patients with early-stage breast cancer were identified from the electronic record and institutional registry. Lymphocyte and monocyte counts were obtained from blood samples at time of diagnosis prior to any chemotherapy. Correlations between lymphocyte and monocyte and recurrence were assessed in the entire cohort and among obese patients, those reporting alcohol consumption and smoking. Competing risk regression was used to analyze time to recurrence. RESULTS: A total of 950 patients with ≥ 5 years of follow-up were identified; 433 had complete data and were eligible for analysis. 293 (68%) had hormone receptor-positive breast cancer, 82 (19%) HER2 positive, and 53 (13%) triple negative. Patients in the highest quintile of lymphocytes compared to the lowest quintile had lower risk of recurrence (subhazard ratio (SHR) = 0.17, 95% CI [0.03-0.93], p = 0.041) while patients in the highest quintile of monocytes had lower risk for recurrence (SHR = 0.19, 95% CI [0.04, 0.92], p = 0.039). Higher monocytes were more strongly associated with lower recurrence among those reporting alcohol consumption (HR = 0.10, 95% CI [0.01, 0.91], p = 0.04). In obese patients, higher lymphocytes were associated with lower risk of recurrence (p = 0.046); in non-obese patients, higher monocytes were associated with lower risk of recurrence (p = 0.02). There were no correlations among patients who reported tobacco use. CONCLUSIONS: High lymphocyte and monocyte counts are associated with lower recurrence rate in early-stage breast cancer, particularly in obese patients and those reporting alcohol consumption.

Economic Burden Among Gay, Bisexual, and Other Men Who Have Sex With Men Living With HIV or Living Without HIV in the Multicenter AIDS Cohort Study.

BACKGROUND: With HIV now considered a chronic disease, economic burden for people living with HIV (LWH) may threaten long-term disease outcomes. We studied associations between economic burden (employment, income, insurance, and financial difficulty) and HIV status for gay, bisexual, and other men who have sex with men (GBMSM) and how economic burden relates to disease progression. SETTING: We analyzed data collected every 6 months through 2015 from GBMSM LWH and GBMSM living without HIV from 2 waves (2001-2003 cohort and 2010+ new recruit cohort) of the Multicenter AIDS Cohort Study. METHODS: Using generalized estimating equations, we first assessed the association between HIV status (exposure) and economic burden indicators since the last study visit (outcomes) of employment (working/student/retired versus not currently working), personal annual income of ≥$10,000, insurance (public/private versus none), and financial difficulty meeting basic expenses. Then among people LWH, we assessed the relationships between economic burden indicators (exposures), risk of progressive immune suppression (CD4 ≤500 cells/uL), and progression to AIDS (CD4 ≤200; outcomes). RESULTS: Of 1721 participants, 59.5% were LWH (n = 1024). GBMSM LWH were 12% less likely to be employed, 16% more likely to have health insurance, and 9% more likely to experience financial difficulty than GBMSM living without HIV. Among GBMSM LWH, employment was associated with a 6% and 32% lower likelihood of immune suppression or progression to AIDS, respectively, and the income was associated with a 15% lower likelihood of progression to AIDS. CONCLUSIONS: Interventions that stabilize employment, income, and offer insurance support may enrich GBMSM LWH's ability to prevent disease progression.

Brief Report: Proportion and Predictors of Adult TB Contacts Accepting HIV Testing During an Active TB Case Finding Intervention in South Africa.

BACKGROUND: Many individuals at risk for HIV may be reached through active TB case finding interventions in areas with highly prevalent co-epidemics of TB/HIV. METHODS: We analyzed data from a cluster-randomized trial of 2 TB case finding strategies: facility-based screening and contact investigation of newly identified TB cases. In both arms, on-site rapid HIV testing was offered to all contacts older than 18 months who did not self-report HIV-positive status. Those who were HIV infected were referred appropriately. All contacts 15 years and older were included in this analysis. RESULTS: Among 2179 contacts identified, 50% (1092) accepted HIV testing and counselling, of whom 6.3% (68) tested HIV-positive. Contacts who were unemployed [adjusted prevalence ratio (aPR) 1.14, 95% confidence interval (CI): 1.04 to 1.25], had not been to a clinic (aPR 1.09, 95% CI: 1.02 to 1.18) or HIV tested (aPR 1.25, 95% CI: 1.14 to 1.39) 6 months before, and those reporting gastrointestinal symptoms (aPR 1.22, 95% CI: 0.98 to 1.52) and genitourinary symptoms (aPR 1.30, 95% CI: 1.17 to 1.45) were significantly associated with accepting HIV testing. Women [adjusted odds ratio (aOR) 2.19, 95% CI: 1.26 to 3.81], individuals with a past history of tuberculosis (aOR 1.96, 95% CI: 0.93 to 4.14), and those not HIV tested 6 months before (aOR 2.20, 95% CI: 1.28 to 3.79) were significantly associated with testing HIV-positive. CONCLUSION: Offering HIV testing in the context of active tuberculosis case finding represents an opportunity to identify a large proportion of previously undiagnosed individuals with HIV in a population that might otherwise not seek testing.

Daratumumab-lenalidomide-dexamethasone vs standard-of-care regimens: Efficacy in transplant-ineligible untreated myeloma.

Daratumumab in combination with lenalidomide-dexamethasone (D-Rd) recently received FDA approval for the treatment of transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). The present PEGASUS study compared progression-free survival (PFS) in patients treated with D-Rd in the MAIA trial and patients treated with common standard-of-care regimens from the Flatiron Health electronic health record-derived deidentified database, which has data from patients treated primarily at community-based oncology practices in the United States. Individual-level patient data from both data sources were used to perform an anchored indirect treatment comparison (ITC) of D-Rd to bortezomib-lenalidomide-dexamethasone (VRd) and bortezomib-dexamethasone (Vd); lenalidomide-dexamethasone (Rd) was the common anchor for the ITC. Hazard ratios (HRs) reflecting direct comparisons of PFS within MAIA (D-Rd vs Rd) and Flatiron Health (VRd vs Rd; Vd vs Rd) were used to make ITCs for D-Rd vs VRd and Vd, respectively. After application of MAIA inclusion/exclusion criteria and propensity-score weighting, the Flatiron Health patients resembled the MAIA trial population on measured baseline characteristics. Based on the direct comparison within MAIA, treatment with D-Rd was associated with a significantly lower risk of progression or death compared to Rd (HR 0.54; 95% CI 0.42, 0.71). Based on the ITCs, D-Rd was associated with a significantly lower risk of progression or death compared to VRd (HR 0.68; 95% CI 0.48, 0.98) and Vd (HR 0.48; 95% CI 0.33, 0.69). In the absence of head-to-head trials comparing D-Rd to VRd or Vd, the present ITC may help inform treatment selection in transplant-ineligible patients with NDMM.