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.

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.

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.

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.

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.

Determinants of infant breastfeeding practices in Nepal: a national study.

Background: Optimal breastfeeding practices, reflected by early initiation and feeding of colostrum, avoidance of prelacteal feeds, and continued exclusivity or predominance of breastfeeding, are critical for assuring proper infant nutrition, growth and development. Methods: We used data from a nationally representative survey in 21 district sites across the Mountains, Hills and Terai (southern plains) of Nepal in 2013. Determinants of early initiation of breastfeeding, feeding of colostrum, prelacteal feeding and predominant breastfeeding were explored in 1015 infants < 12 months of age. Prelacteal feeds were defined as food/drink other than breast milk given to newborns in first 3 days. Predominant breastfeeding was defined as a child < 6 months of age is mainly breastfed, not fed solid/semi-solid foods, infant formula or non-human milk, in the past 7 days. Adjusted prevalence ratios (APR) and 95% confidence intervals (CI) were estimated, using log Poisson regression models with robust variance for clustering. Results: The prevalence of breastfeeding within an hour of birth, colostrum feeding, prelacteal feeding and predominant breastfeeding was 41.8, 83.5, 32.7 and 57.2% respectively. Compared to infants not fed prelacteal feeds, infants given prelacteal feeds were 51% less likely to be breastfed within the first hour of birth (APR 0.49; 95% CI 0.36, 0.66) and 55% less likely to be predominantly breastfed (APR 0.45; 95% CI 0.32, 0.62). Infants reported to have received colostrum were more likely to have begun breastfeeding within an hour of birth (APR 1.26; 95% CI 1.04, 1.54) compared to those who did not receive colostrum. Infants born to mothers ≥ 20 years of age were less likely than adolescent mothers to initiate breastfeeding within 1 hour of birth. Infants in the Terai were 10% less likely to have received colostrum (APR 0.90; 95% CI 0.83, 0.97) and 2.72 times more likely to have received prelacteal feeds (APR 2.72; 95% CI 1.67, 4.45) than those in the Mountains. Conclusions: Most infants in Nepal receive colostrum but less than half initiate breastfeeding within an hour of birth and one-third are fed prelacteal feeds, which may negatively affect breastfeeding and health throughout early infancy.

Effect of Birth Preparedness on Institutional Delivery in Semiurban Ethiopia: A Cross-Sectional Study.

BACKGROUND: Ethiopia has one of the lowest rates of facility delivery and is promoting birth preparedness among pregnant women through its community health services to increase the rate of institutional delivery and reduce maternal mortality. Observational studies of birth preparedness in Ethiopia have thus far only reported the marginal effect of birth preparedness when controlling for other factors, such as parity and education. OBJECTIVES: In this cross-sectional study, we use propensity score modeling to estimate the average population-level effect of birth preparedness on the likelihood of delivering at a facility. METHODS: We conducted secondary analysis of household survey data collected from 215 women with a recent live birth within the catchment areas of 10 semi-urban health centers. A mother was considered well prepared for birth if she reported completing four of the following six actions: identified a skilled provider, identified an institution, saved money, identified transport, prepared clean delivery materials, and prepared food. We performed unadjusted and multivariate logistic regression analyses, with and without propensity score weighting, to assess the relationship between birth preparedness and institutional delivery. FINDINGS: One hundred respondents (47%) delivered in an institution, and over two-thirds (151, 71%) were considered well prepared for birth. Institutional delivery was more common among women who were considered well prepared (57%) versus those who were considered not well prepared (19%). In the model with propensity score weighting, women who were well prepared for birth had 3.83 times higher odds of delivering at a facility (95% CI: 1.41-10.40, p-value = 0.010). CONCLUSIONS: This study contributes to existing evidence supporting the inclusion of antenatal birth preparedness counseling as a part of an antenatal care package for promoting institutional delivery. Important gaps remain in operationalizing the definition of birth preparedness and understanding the pathway from exposure to outcome.

Interactive Malaria Education Intervention and Its Effect on Community Participant Knowledge: The Malaria Awareness Program in Vhembe District, Limpopo, South Africa.

Malaria is preventable and treatable, yet remains the most prevalent parasitic endemic disease in Africa. This article analyzes prospective observational data from the Malaria Awareness Program (MAP), an interactive malaria education initiative led by home-based care workers to improve participant knowledge of malaria as a precursor to increased uptake of malaria control interventions in the Vhembe District, Limpopo, South Africa. Between 2012 and 2016, 1,330 individuals participated in MAP. MAP's effectiveness was measured through pre- and post-participation surveys assessing knowledge in malaria transmission, symptoms, prevention, and treatment. The primary analysis assessed differences in knowledge between individuals who completed MAP ( n = 499) and individuals who did not complete MAP ( n = 399). The adjusted odds of correct malaria knowledge score versus partially correct or incorrect score among MAP completers was 3.3 and 2.8 times greater for transmission and prevention, respectively ( p values<.001). A subanalysis assessed knowledge improvement among participants who completed both pre- and post-MAP intervention surveys ( n = 266). There was a 21.4% and 10.5% increase in the proportion of participants who cited correct malaria transmission and prevention methods, respectively. Future research should assess behavioral changes toward malaria prevention and treatment as a result of an intervention and examine incidence changes in the region.

Changing hearts and minds: Results from a multi-country gender and sexual diversity training.

Engaging key populations, including gender and sexual minorities, is essential to meeting global targets for reducing new HIV infections and improving the HIV continuum of care. Negative attitudes toward gender and sexual minorities serve as a barrier to political will and effective programming for HIV health services. The President's Emergency Plan for AIDS Relief (PEPFAR), established in 2003, provided Gender and Sexual Diversity Trainings for 2,825 participants including PEPFAR staff and program implementers, U.S. government staff, and local stakeholders in 38 countries. The outcomes of these one-day trainings were evaluated among a subset of participants using a mixed methods pre- and post-training study design. Findings suggest that sustainable decreases in negative attitudes toward gender and sexual minorities are achievable with a one-day training.

Comparing longitudinal CD4 responses to cART among non-perinatally HIV-infected youth versus adults: Results from the HIVRN Cohort.

BACKGROUND: Youth have residual thymic tissue and potentially greater capacity for immune reconstitution than adults after initiation of combination antiretroviral therapy (cART). However, youth face behavioral and psychosocial challenges that may make them more likely than adults to delay ART initiation and less likely to attain similar CD4 outcomes after initiating cART. This study compared CD4 outcomes over time following cART initiation between ART-naïve non-perinatally HIV-infected (nPHIV) youth (13-24 years-old) and adults (≥25-44 years-old). METHODS: Retrospective analysis of ART-naïve nPHIV individuals 13-44 years-old, who initiated their first cART between 2008 and 2011 at clinical sites in the HIV Research Network. A linear mixed model was used to assess the association between CD4 levels after cART initiation and age (13-24, 25-34, 35-44 years), accounting for random variation within participants and between sites, and adjusting for key variables including gender, race/ethnicity, viral load, gaps in care (defined as > 365 days between CD4 tests), and CD4 levels prior to cART initiation (baseline CD4). RESULTS: Among 2,595 individuals (435 youth; 2,160 adults), the median follow-up after cART initiation was 179 weeks (IQR 92-249). Baseline CD4 was higher for youth (320 cells/mm3) than for ages 25-34 (293) or 35-44 (258). At 239 weeks after cART initiation, median unadjusted CD4 was higher for youth than adults (576 vs. 539 and 476 cells/mm3, respectively), but this difference was not significant when baseline CD4 was controlled. Compared to those with baseline CD4 ≤200 cells/mm3, individuals with baseline CD4 of 201-500 and >500 cells/mm3 had greater predicted CD4 levels: 390, 607, and 831, respectively. Additionally, having no gaps in care and higher viral load were associated with better CD4 outcomes. CONCLUSIONS: Despite having residual thymic tissue, youth attain similar, not superior, CD4 gains as adults. Early ART initiation with minimal delay is as essential to optimizing outcomes for youth as it is for their adult counterparts.

Advanced-stage hepatocellular carcinoma with portal vein thrombosis: conventional versus drug-eluting beads transcatheter arterial chemoembolization.

OBJECTIVES: Our study sought to compare the overall survival in patients with hepatocellular carcinoma (HCC) and portal venous thrombosis (PVT), treated with either conventional trans-arterial chemoembolization (cTACE) or drug-eluting beads (DEB) TACE. METHODS: This retrospective analysis included a total of 133 patients, treated without cross-over and compared head-to-head by means or propensity score weighting. Mortality was compared using survival analysis upon propensity score weighting. Adverse events and liver toxicity grade ≥3 were recorded and reported for each TACE. In order to compare with historical sorafenib studies, a sub-group analysis was performed and included patients who fulfilled the SHARP inclusion criteria. RESULTS: The median overall survival (MOS) of the entire cohort was 4.53 months (95 % CI, 3.63-6.03). MOS was similar across treatment arms, no significant difference between cTACE (N = 95) and DEB-TACE (N = 38) was observed (MOS of 5.0 vs. 3.33 months, respectively; p = 0.157). The most common adverse events after cTACE and DEB- TACE, respectively, were as follows: post-embolization syndrome [N = 57 (30.0 %) and N = 38 (61.3 %)], diarrhea [N = 3 (1.6 %) and N = 3 (4.8 %)], and encephalopathy [N = 11 (5.8 %) and N = 2 (3.2 %)]. CONCLUSION: Our retrospective study could not reveal a difference in toxicity and efficiency between cTACE and DEB-TACE for treatment of advanced stage HCC with PVT. KEY POINTS: • Conventional TACE (cTACE) and drug-eluting-beads TACE (DEB-TACE) demonstrated equal safety profiles. • Survival rates after TACE are similar to patients treated with sorafenib. • Child-Pugh class and tumor burden are reliable predictors of survival.

The Use of Indwelling Tunneled Pleural Catheters for Recurrent Pleural Effusions in Patients With Hematologic Malignancies: A Multicenter Study.

BACKGROUND: Malignant pleural effusion is a common complication of advanced malignancies. Indwelling tunneled pleural catheter (IPC) placement provides effective palliation but can be associated with complications, including infection. In particular, hematologic malignancy and the associated immunosuppressive treatment regimens may increase infectious complications. This study aimed to review outcomes in patients with hematologic malignancy undergoing IPC placement. METHODS: A retrospective multicenter study of IPCs placed in patients with hematologic malignancy from January 2009 to December 2013 was performed. Inclusion criteria were recurrent, symptomatic pleural effusion and an underlying diagnosis of hematologic malignancy. Records were reviewed for patient demographics, operative reports, and pathology, cytology, and microbiology reports. RESULTS: Ninety-one patients (mean ± SD age, 65.4 ± 15.4 years) were identified from eight institutions. The mean × SD in situ dwell time of all catheters was 89.9 ± 127.1 days (total, 8,160 catheter-days). Seven infectious complications were identified, all of the pleural space. All patients were admitted to the hospital for treatment, with four requiring additional pleural procedures. Two patients died of septic shock related to pleural infection. CONCLUSIONS: We present, to our knowledge, the largest study examining clinical outcomes related to IPC placement in patients with hematologic malignancy. An overall 7.7% infection risk and 2.2% mortality were identified, similar to previously reported studies, despite the significant immunosuppression and pancytopenia often present in this population. IPC placement appears to remain a reasonable clinical option for patients with recurrent pleural effusions related to hematologic malignancy.