Childhood growth during recovery from acute illness in Africa and South Asia: a secondary analysis of the childhood acute illness and nutrition (CHAIN) prospective cohort.

Background: Growth faltering is well-recognized during acute childhood illness and growth acceleration during convalescence, with or without nutritional therapy, may occur. However, there are limited recent data on growth after hospitalization in low- and middle-income countries. Methods: We evaluated growth following hospitalization among children aged 2-23 months in sub-Saharan Africa and South Asia. Between November 2016 and January 2019, children were recruited at hospital admission and classified as: not-wasted (NW), moderately-wasted (MW), severely-wasted (SW), or having nutritional oedema (NO). We describe earlier (discharge to 45-days) and later (45- to 180-days) changes in length-for-age [LAZ], weight-for-age [WAZ], mid-upper arm circumference [MUACZ], weight-for-length [WLZ] z-scores, and clinical, nutritional, and socioeconomic correlates. Findings: We included 2472 children who survived to 180-days post-discharge: NW, 960 (39%); MW, 572 (23%); SW, 682 (28%); and NO, 258 (10%). During 180-days, LAZ decreased in NW (-0.27 [-0.36, -0.19]) and MW (-0.23 [-0.34, -0.11]). However, all groups increased WAZ (NW, 0.21 [95% CI: 0.11, 0.32]; MW, 0.57 [0.44, 0.71]; SW, 1.0 [0.88, 1.1] and NO, 1.3 [1.1, 1.5]) with greatest gains in the first 45-days. Of children underweight (<-2 WAZ) at discharge, 66% remained underweight at 180-days. Lower WAZ post-discharge was associated with age-inappropriate nutrition, adverse caregiver characteristics, small size at birth, severe or moderate anaemia, and chronic conditions, while lower LAZ was additionally associated with household-level exposures but not with chronic medical conditions. Interpretation: Underweight and poor linear growth mostly persisted after an acute illness. Beyond short-term nutritional supplementation, improving linear growth post-discharge may require broader individual and family support. Funding: Bill & Melinda Gates FoundationOPP1131320; National Institute for Health ResearchNIHR201813.

Characterizing provider-led adaptations to mobile phone delivery of the Adolescent Transition Package (ATP) in Kenya using the Framework for Reporting Adaptations and Modifications to Evidence-based Implementation Strategies (FRAME-IS): a mixed methods approach.

BACKGROUND: The COVID-19 pandemic resulted in disruptions to routine HIV services for youth living with HIV (YLH), provoking rapid adaptation to mitigate interruptions in care. The Adolescent Transition to Adult Care for HIV-infected adolescents (ATTACH) study (NCT03574129) was a hybrid I cluster randomized trial testing the effectiveness of a healthcare worker (HCW)-delivered disclosure and transition intervention - the Adolescent Transition Package (ATP). During the pandemic, HCWs leveraged phone delivery of the ATP and were supported to make adaptations. We characterized real-time, provider-driven adaptations made to support phone delivery of the ATP. METHODS: We conducted continuous quality improvement (CQI) meetings with HCWs involved in phone delivery of the ATP at 10 intervention sites. CQI meetings used plan-do-study-act (PDSA) cycles and were audio-recorded. Adaptations were coded by two-independent coders using the Framework for Reporting Adaptations and Modifications to Evidence-based Implementation Strategies (FRAME-IS). Adaptation testing outcomes (adopt, retest, or abandon) and provider experience implementing the adaptations were also recorded. We summarized adaptation characteristics, provider experience, and outcomes. RESULTS: We identified 72 adaptations, 32 were unique. Overall, adaptations included modification to context (53%, n = 38), content (49%, n = 35), and evaluation processes (13%, n = 9). Context adaptations primarily featured changes to personnel, format, and setting, while content and evaluation adaptations were frequently achieved by simple additions, repetition, and tailoring/refining of the phone delivery strategy. Nine adaptations involved abandoning, then returning to phone delivery. HCWs sought to increase reach, improve fidelity, and intervention fit within their context. Most adaptations (96%, n = 69) were perceived to increase the feasibility of phone delivery when compared to before the changes were introduced, and HCWs felt 83% (n = 60) of adaptations made phone delivery easier. Most adaptations were either incorporated into routine workflows (47%) or tested again (47%). CONCLUSION: Adaptation of phone delivery was a feasible and effective way of addressing challenges with continuity of care for YLH during the COVID-19 pandemic. Adaptations were primarily context adaptions. While FRAME-IS was apt for characterizing adaptations, more use cases are needed to explore the range of its utility. TRIAL REGISTRATION: Trial registered on ClinicalTrial.gov as NCT03574129.

Demand creation for HIV testing services: A systematic review and meta-analysis.

BACKGROUND: HIV testing services (HTS) are the first steps in reaching the UNAIDS 95-95-95 goals to achieve and maintain low HIV incidence. Evaluating the effectiveness of different demand creation interventions to increase uptake of efficient and effective HTS is useful to prioritize limited programmatic resources. This review was undertaken to inform World Health Organization (WHO) 2019 HIV testing guidelines and assessed the research question, "Which demand creation strategies are effective for enhancing uptake of HTS?" focused on populations globally. METHODS AND FINDINGS: The following electronic databases were searched through September 28, 2021: PubMed, PsycInfo, Cochrane CENTRAL, CINAHL Complete, Web of Science Core Collection, EMBASE, and Global Health Database; we searched IAS and AIDS conferences. We systematically searched for randomized controlled trials (RCTs) that compared any demand creation intervention (incentives, mobilization, counseling, tailoring, and digital interventions) to either a control or other demand creation intervention and reported HTS uptake. We pooled trials to evaluate categories of demand creation interventions using random-effects models for meta-analysis and assessed study quality with Cochrane's risk of bias 1 tool. This study was funded by the WHO and registered in Prospero with ID CRD42022296947. We screened 10,583 records and 507 conference abstracts, reviewed 952 full texts, and included 124 RCTs for data extraction. The majority of studies were from the African (N = 53) and Americas (N = 54) regions. We found that mobilization (relative risk [RR]: 2.01, 95% confidence interval [CI]: [1.30, 3.09], p < 0.05; risk difference [RD]: 0.29, 95% CI [0.16, 0.43], p < 0.05, N = 4 RCTs), couple-oriented counseling (RR: 1.98, 95% CI [1.02, 3.86], p < 0.05; RD: 0.12, 95% CI [0.03, 0.21], p < 0.05, N = 4 RCTs), peer-led interventions (RR: 1.57, 95% CI [1.15, 2.15], p < 0.05; RD: 0.18, 95% CI [0.06, 0.31], p < 0.05, N = 10 RCTs), motivation-oriented counseling (RR: 1.53, 95% CI [1.07, 2.20], p < 0.05; RD: 0.17, 95% CI [0.00, 0.34], p < 0.05, N = 4 RCTs), short message service (SMS) (RR: 1.53, 95% CI [1.09, 2.16], p < 0.05; RD: 0.11, 95% CI [0.03, 0.19], p < 0.05, N = 5 RCTs), and conditional fixed value incentives (RR: 1.52, 95% CI [1.21, 1.91], p < 0.05; RD: 0.15, 95% CI [0.07, 0.22], p < 0.05, N = 11 RCTs) all significantly and importantly (≥50% relative increase) increased HTS uptake and had medium risk of bias. Lottery-based incentives and audio-based interventions less importantly (25% to 49% increase) but not significantly increased HTS uptake (medium risk of bias). Personal invitation letters and personalized message content significantly but not importantly (<25% increase) increased HTS uptake (medium risk of bias). Reduced duration counseling had comparable performance to standard duration counseling (low risk of bias) and video-based interventions were comparable or better than in-person counseling (medium risk of bias). Heterogeneity of effect among pooled studies was high. This study was limited in that we restricted to randomized trials, which may be systematically less readily available for key populations; additionally, we compare only pooled estimates for interventions with multiple studies rather than single study estimates, and there was evidence of publication bias for several interventions. CONCLUSIONS: Mobilization, couple- and motivation-oriented counseling, peer-led interventions, conditional fixed value incentives, and SMS are high-impact demand creation interventions and should be prioritized for programmatic consideration. Reduced duration counseling and video-based interventions are an efficient and effective alternative to address staffing shortages. Investment in demand creation activities should prioritize those with undiagnosed HIV or ongoing HIV exposure. Selection of demand creation interventions must consider risks and benefits, context-specific factors, feasibility and sustainability, country ownership, and universal health coverage across disease areas.

Religiosity and Stigmatization Related to Mental Illness Among African Americans and Black Immigrants: Cross-Sectional Observational Study and Moderation Analysis.

ABSTRACT: Stigma about mental illness is a known barrier to engagement in mental health services. We conducted an online cross-sectional study, aiming to estimate the associations between religiosity and mental illness stigma among Black adults ( n = 269, ages 18-65 years) in the United States. After adjusting for demographic factors (age, education, and ethnicity), respondents with higher attendance at religious services or greater engagement in religious activities ( e.g. , prayer, meditation, or Bible study) reported greater proximity to people living with mental health problems (rate ratio [RR], 1.72; 95% confidence interval [CI], 1.14-2.59 and RR, 1.82; 95% CI, 1.18-2.79, respectively). Despite reporting greater past or current social proximity, respondents with higher religiosity indices also reported greater future intended stigmatizing behavior (or lower future intended social proximity) (RR, 0.92-0.98). Focusing specifically on future intended stigmatizing behavior and the respondent's level of religiosity, age, and ethnicity may be critical for designing effective stigma-reducing interventions for Black adults.

Efficiency of 6-month PrEP dispensing with HIV self-testing in Kenya: an open-label, randomised, non-inferiority, implementation trial.

BACKGROUND: Oral pre-exposure prophylaxis (PrEP) for HIV prevention is highly effective and is being implemented at scale at health clinics throughout sub-Saharan Africa. However, barriers to clinic-based PrEP delivery remain. We aimed to establish the efficiency of semiannual PrEP clinic visits supplemented with interim home-based HIV self-testing (HIVST) versus standard of care for HIV testing, drug refilling, and adherence among PrEP users. METHODS: This was a randomised, open-label, non-inferiority trial done at the Partners in Health and Research Development clinic in Thika, Kenya. Eligible participants were HIV-negative adults (≥18 years) at risk of acquiring HIV who had started PrEP at least 1 month before enrolment. Participants were randomly assigned (1:1:1) to 6-month PrEP dispensing plus interim blood-based HIVST (with biannual clinic visits), 6-month PrEP dispensing plus interim oral fluid-based HIVST (with biannual clinic visits), or standard of care PrEP delivery (3-month PrEP dispensing with quarterly clinic visits). The three coprimary outcomes, measured at 6 months, were HIV testing (any testing between enrolment and the 6-month visit), PrEP refilling, and PrEP adherence (detectable tenofovir diphosphate concentration in dried blood spots). All analyses were done according to the intention-to-treat principle. We used binomial regression models to estimate risk differences and one-sided 95% CIs. 6-month PrEP dispensing was considered non-inferior to standard of care if the lower limit bound of the one-sided 95% CI was greater than or equal to -10%. This study is registered with ClinicalTrials.gov, NCT03593629. FINDINGS: Between May 28, 2018, and Feb 24, 2020, 495 participants were enrolled: 165 men and 130 women in HIV serodifferent couples and 200 singly enrolled women. 166 participants were randomly assigned to the standard of care group, 163 to the 6-month PrEP dispensing plus oral-fluid HIVST group, and 166 to the 6-month PrEP dispensing plus blood-based HIVST group. At 6 months, 274 (83%) of 329 participants in the combined 6-month PrEP dispensing group had tested for HIV compared with 140 (84%) of 166 participants in the standard of care group (risk difference -1·15%, 95% CI lower bound -6·89). Among participants in the combined 6-month PrEP dispensing group, 257 (78%) participants refilled PrEP compared with 134 (81%) participants in the standard of care group (-2·60%, -8·88), and 200 (61%) participants were adherent to PrEP compared with 95 (57%) participants in the standard of care group (2·37%, -5·05). No participants acquired HIV during the study. INTERPRETATION: 6-month PrEP dispensing with HIVST for interim testing reduced the number of PrEP clinic visits in half without compromising HIV testing, retention, or adherence. FUNDING: US National Institute of Mental Health.

A mixed method multi-country assessment of barriers to implementing pediatric inpatient care guidelines.

INTRODUCTION: Accelerating progress in reducing child deaths is needed in order to achieve the Sustainable Development Goal child mortality target. This will require a focus on vulnerable children-including young children, those who are undernourished or with acute illnesses requiring hospitalization. Improving adherence to inpatient guidelines may be an important strategy to reduce child mortality, including among the most vulnerable. The aim of our assessment of nine sub-Saharan African and South Asian hospitals was to determine adherence to pediatric inpatient care recommendations, in addition to capacity for and barriers to implementation of guideline-adherent care prior to commencing the Childhood Acute Illness and Nutrition (CHAIN) Cohort study. The CHAIN Cohort study aims to identify modifiable risk factors for poor inpatient and post discharge outcomes above and beyond implementation of guidelines. METHODS: Hospital infrastructure, staffing, durable equipment, and consumable supplies such as medicines and laboratory reagents, were evaluated through observation and key informant interviews. Inpatient medical records of 2-23 month old children were assessed for adherence to national and international guidelines. The records of children with severe acute malnutrition (SAM) were oversampled to reflect the CHAIN study population. Seven core adherence indicators were examined: oximetry and oxygen therapy, fluids, anemia diagnosis and transfusion, antibiotics, malaria testing and antimalarials, nutritional assessment and management, and HIV testing. RESULTS: All sites had facilities and equipment necessary to implement care consistent with World Health Organization and national guidelines. However, stockouts of essential medicines and laboratory reagents were reported to be common at some sites, even though they were mostly present during the assessment visits. Doctor and nurse to patient ratios varied widely. We reviewed the notes of 261 children with admission diagnoses of sepsis (17), malaria (47), pneumonia (70), diarrhea (106), and SAM (119); 115 had multiple diagnoses. Adherence to oxygen therapy, antimalarial, and malnutrition refeeding guidelines was >75%. Appropriate antimicrobials were prescribed for 75% of antibiotic-indicative conditions. However, 20/23 (87%) diarrhea and 20/27 (74%) malaria cases without a documented indication were prescribed antibiotics. Only 23/122 (19%) with hemoglobin levels meeting anemia criteria had recorded anemia diagnoses. HIV test results were infrequently documented even at hospitals with universal screening policies (66/173, 38%). Informants at all sites attributed inconsistent guideline implementation to inadequate staffing. CONCLUSION: Assessed hospitals had the infrastructure and equipment to implement guideline-consistent care. While fluids, appropriate antimalarials and antibiotics, and malnutrition refeeding adherence was comparable to published estimates from low- and high-resource settings, there were inconsistencies in implementation of some other recommendations. Stockouts of essential therapeutics and laboratory reagents were a noted barrier, but facility staff perceived inadequate human resources as the primary constraint to consistent guideline implementation.

Familial aggregation of high tumor necrosis factor alpha levels in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) patients frequently have high circulating tumor necrosis factor alpha (TNF-α) levels. We explored circulating TNF-α levels in SLE families to determine whether high levels of TNF-α were clustered in a heritable pattern. We measured TNF-α in 242 SLE patients, 361 unaffected family members, 23 unaffected spouses of SLE patients, and 62 unrelated healthy controls. Familial correlations and relative recurrence risk rates for the high TNF-α trait were assessed. SLE-affected individuals had the highest TNF-α levels, and TNF-α was significantly higher in unaffected first degree relatives than healthy unrelated subjects (P = 0.0025). No Mendelian patterns were observed, but 28.4% of unaffected first degree relatives of SLE patients had high TNF-α levels, resulting in a first degree relative recurrence risk of 4.48 (P = 2.9 × 10⁻5). Interestingly, the median TNF-α value in spouses was similar to that of the first degree relatives. Concordance of the TNF-α trait (high versus low) in SLE patients and their spouses was strikingly high at 78.2%. These data support a role for TNF-α in SLE pathogenesis, and TNF-α levels may relate with heritable factors. The high degree of concordance in SLE patients and their spouses suggests that environmental factors may also play a role in the observed familial aggregation.

Large-scale analysis of tumor necrosis factor α levels in systemic lupus erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE) disease manifestations are highly variable among patients, and the prevalence of individual clinical features differs significantly by ancestry. Serum tumor necrosis factor α (TNFα) levels are elevated in some SLE patients and may play a role in disease pathogenesis. The aim of this study was to look for associations between serum TNFα levels, clinical manifestations of SLE, autoantibodies, and serum interferon-α (IFNα) levels in a large multiancestral SLE cohort. METHODS: We studied serum TNFα levels in 653 SLE patients (214 African Americans, 298 European Americans, and 141 Hispanic Americans). TNFα was measured using an enzyme-linked immunosorbent assay, and IFNα was measured with a functional reporter cell assay. Stratified and multivariate analyses were used to detect associations in each ancestral background separately, with meta-analysis when appropriate. RESULTS: Serum TNFα levels were significantly higher in SLE patients than in non-autoimmune disease controls (P < 5.0 × 10(-3) for each ancestral background). High serum TNFα levels were positively correlated with high serum IFNα levels when tested in the same sample across all ancestral backgrounds (odds ratio range 1.76-1.86, P = 4.8 × 10(-3) by Fisher's combined probability test). While serum TNFα levels alone did not differ significantly among SLE patients of different ancestral backgrounds, the proportion of patients with concurrently high levels of TNFα and IFNα was highest in African Americans and lowest in European Americans (P = 5.0 × 10(-3) ). Serum TNFα levels were not associated with autoantibodies, clinical criteria for the diagnosis of SLE, or age at the time of sampling. CONCLUSION: Serum TNFα levels are high in many SLE patients, and we observed a positive correlation between serum TNFα and IFNα levels. These data support a role for TNFα in the pathogenesis of SLE across all ancestral backgrounds and suggest important cytokine subgroups within the disease.