Preeclampsia, Fetal Growth Restriction, and 24-Month Neurodevelopment in Very Preterm Infants.

Importance: Preeclampsia has direct influences on a developing fetus and may impact postnatal health, and fetal growth restriction (FGR) is often seen co-occurring with preeclampsia. The development of children born very preterm after preeclampsia diagnosis with and without FGR is not well characterized. Objective: To examine the associations of preeclampsia and FGR with developmental and/or behavioral outcomes in a cohort of very preterm infants. Design, Setting, and Participants: In this cohort study, infants in the prospective Neonatal Neurobehavior and Outcomes in Very Preterm Infants study were enrolled between April 2014 and June 2016 from 9 US university-affiliated neonatal intensive care units (NICUs). Eligible infants were born before 30 weeks' gestation. Infants were excluded for any major congenital anomalies and for maternal age younger than 18 years or cognitive impairment impacting the ability to provide informed consent. Data analysis was performed from November 2023 to January 2024. Exposure: Maternal preeclampsia and FGR in very preterm infants. Main Outcomes and Measures: The Bayley-III cognition, motor, and language scores less than 85 (-1 SD) indicated developmental delay. Child Behavior Checklist/Preschool 1.5-5 T-scores greater than or equal to 64 for internalizing, externalizing, or total problems indicated clinical importance. Results: Of 704 infants enrolled, 529 (mean [SD] gestational age, 27.0 [1.9] weeks; 287 male [54.3%]) were studied at 24-month follow-up. A total of 94 infants' mothers had preeclampsia (23.2%), and 46 infants (8.7%) had FGR. In adjusted models, preeclampsia was not associated with Bayley-III (cognitive, B = 3.43 [95% CI, -0.19 to 6.66]; language, B = 3.92 [95% CI, 0.44 to 7.39]; motor, B = 1.86 [95% CI, -1.74 to 5.47]) or Child Behavior Checklist/Preschool 1.5-5 (internalizing, B = -0.08 [95% CI, -2.58 to 2.73]; externalizing, B = 0.69 [95% CI, -1.76 to 3.15]; total, B = 0.21 [95% CI, -2.48 to 2.91]) outcomes. FGR was associated with significantly lower Bayley-III scores (cognitive, B = -8.61 [95% CI, -13.33 to -3.89]; language, B = -8.29 [95% CI, -12.95 to -3.63]; motor, B = -7.60 [95% CI, -12.40 to -2.66]), regardless of preeclampsia status. Conclusions and Relevance: In this cohort study of preterm infants, preeclampsia was not associated with developmental and/or behavioral outcomes, but infants with FGR may be prone to developmental delays. These findings suggest future areas of research for understanding the roles of preeclampsia and FGR separately and together in early child development for preterm infants.

Exploring the Relationship Between Anticipated Stigma and Community Shared Concerns about HIV on Defaulting from HIV Care in Rural South Africa.

Although stigma has been associated with people living with HIV defaulting from care, there is a gap in understanding the specific impact of individual stigma and community-level concern about HIV on defaulting. Methods: This is a secondary analysis of a unique dataset that links health facility-based medical records to a population-representative community survey conducted in 2018 in rural Mpumalanga province, South Africa. We used the parametric g-formula to estimate associations among individual anticipated stigma, low perceived community and local leader concern about HIV, and defaulting from care in the prior year. In addition, we estimated the population-level effects of intervening to reduce stigma and increase concern on defaulting. Results: Among 319 participants on treatment, 42 (13.2%) defaulted from care during the prior year. Anticipated stigma (risk ratio [RR] 1.22, 95% confidence interval [CI]: 0.72, 2.74), low perceived concern about HIV/AIDS from community leadership (RR 1.12, 95% CI 0.76, 3.38), and low shared concerns about HIV/AIDS in the community (RR 1.37; 95% CI 0.79, 3.07) were not significantly associated with default. Hypothetical population intervention effects to remove individual anticipated stigma and low community concerns yielded small reductions in default (~1% reduction). Conclusions: In this sample, we found limited impact of reducing anticipated stigma and increasing shared concern about HIV on retention in care. Future studies should consider the limitations of this study by examining the influence of other sources of stigma in more detail and assessing how perceptions of stigma and concern impact the full HIV testing and care cascade.

Correlates of viral suppression among sexual minority men and transgender women living with HIV in Mpumalanga, South Africa.

Sexual minority men (SMM) and transgender women in South Africa engage in HIV care at lower rates than other persons living with HIV and may experience population-specific barriers to HIV treatment and viral suppression (VS). As part of a pilot trial of an SMM-tailored peer navigation (PN) intervention in Ehlanzeni district, South Africa, we assessed factors associated with ART use and VS among SMM at trial enrolment. A total of 103 HIV-positive SMM and transgender women enrolled in the pilot trial. Data on clinical visits and ART adherence were self-reported. VS status was verified through laboratory analysis (<1000 copies/ml). We assessed correlates of VS at baseline using Poisson generalized linear model (GLM) with a log link function, including demographic, psychosocial, clinical, and behavioral indicators. Among participants, 52.4% reported ART use and only 42.2% of all participants had evidence of VS. Of the 49.5% who reported optimal engagement in HIV care (consistent clinic visits with pills never missed for ≥ 4 consecutive days) in the past 3-months, 56.0% were virally suppressed. In multivariable analysis, SMM were significantly more likely to be virally suppressed when they were ≥ 25 years of age (Adjusted prevalence ratio [APR] = 2.0, CI 95%:1.0-3.8); in a relationship but not living with partner, as compared to married, living together, or single (APR = 1.7, CI 95%:1.0-2.7), and optimally engaged in care (APR = 2.1, 95% CI:1.3-3.3). Findings indicate a need for targeted treatment and care support programming, especially for SMM and transgender women who are young and married/living with their partners to improve treatment outcomes among this population.

Reducing intersectional stigma among transgender women in Brazil to promote uptake of HIV testing and PrEP: study protocol for a randomised controlled trial of Manas por Manas.

INTRODUCTION: Globally, transgender ('trans') women experience extreme social and economic marginalisation due to intersectional stigma, defined as the confluence of stigma that results from the intersection of social identities and positions among those who are oppressed multiple times. Among trans women, gender-based stigma intersects with social positions such as engagement in sex work and substance use, as well as race-based stigma to generate a social context of vulnerability and increased risk of HIV acquisition. In Brazil, trans women are the 'most at-risk' group for HIV, with 55 times higher estimated odds of HIV infection than the general population; further, uptake of HIV testing and pre-exposure prophylaxis (PrEP) among trans women is significantly lower than other at-risk groups. Through extensive formative work, we developed Manas por Manas, a multilevel intervention using HIV prevention strategies with demonstrated feasibility and acceptability by trans women in Brazil, to address intersectional stigma and increase engagement in the HIV prevention continuum. METHODS AND ANALYSIS: We are conducting a two-arm randomised wait-list controlled trial of the intervention's efficacy in São Paulo, Brazil, to improve uptake of HIV testing and PrEP among transgender women (N=400). The primary outcomes are changes in HIV testing (self-testing and clinic based), changes in PrEP uptake and changes in PrEP persistence at baseline and follow-up assessment for 12 months at 3-month intervals. ETHICS AND DISSEMINATION: This study was approved by University of California, San Francisco Institutional Review Board (15-17910) and Comissão Nacional de Ética em Pesquisa (Research Ethics National Commission, CAAE: 25215219.8.0000.5479) in Brazil. Participants provided informed consent before enrolment. We are committed to collaboration with National Institutes of Health officials, other researchers, and health and social services communities for rapid dissemination of data and sharing of materials. The results will be published in peer-reviewed academic journals and scientific presentations. TRIAL REGISTRATION NUMBER: NCT03081559.

Adapting and testing measures of organizational context in primary care clinics in KwaZulu-Natal, South Africa.

BACKGROUND: Implementation science frameworks situate intervention implementation and sustainment within the context of the implementing organization and system. Aspects of organizational context such as leadership have been defined and measured largely within US health care settings characterized by decentralization and individual autonomy. The relevance of these constructs in other settings may be limited by differences like collectivist orientation, resource constraints, and hierarchical power structures. We aimed to adapt measures of organizational context in South African primary care clinics. METHODS: We convened a panel of South African experts in social science and HIV care delivery and presented implementation domains informed by existing frameworks and prior work in South Africa. Based on panel input, we selected contextual domains and adapted candidate items. We conducted cognitive interviews with 25 providers in KwaZulu-Natal Province to refine measures. We then conducted a cross-sectional survey of 16 clinics with 5-20 providers per clinic (N = 186). We assessed reliability using Cronbach's alpha and calculated interrater agreement (awg) and intraclass correlation coefficient (ICC) at the clinic level. Within clinics with moderate agreement, we calculated correlation of clinic-level measures with each other and with hypothesized predictors - staff continuity and infrastructure - and a clinical outcome, patient retention on antiretroviral therapy. RESULTS: Panelists emphasized contextual factors; we therefore focused on elements of clinic leadership, stress, cohesion, and collective problem solving (critical consciousness). Cognitive interviews confirmed salience of the domains and improved item clarity. After excluding items related to leaders' coordination abilities due to missingness and low agreement, all other scales demonstrated individual-level reliability and at least moderate interrater agreement in most facilities. ICC was low for most leadership measures and moderate for others. Measures tended to correlate within facility, and higher stress was significantly correlated with lower staff continuity. Organizational context was generally more positively rated in facilities that showed consistent agreement. CONCLUSIONS: As theorized, organizational context is important in understanding program implementation within the South African health system. Most adapted measures show good reliability at individual and clinic levels. Additional revision of existing frameworks to suit this context and further testing in high and low performing clinics is warranted.

Results of the Sukuma Ndoda ("Stand up, Man") HIV Self-Screening and Assisted Linkage to Care Project in Johannesburg: A Quasi-Experimental Pre-Post Evaluation.

BACKGROUND: HIV testing rates among South African men lag behind rates for women and national targets. Community-based HIV self-screening (HIVSS) distribution and follow-up by community health workers (CHWs) is a scalable option to increase testing coverage, diagnosis, and treatment initiation. We provided HIVSS and assisted linkage to care to men not recently tested (within the past 12 months) residing in high-HIV-burden areas of Johannesburg. METHODS: CHWs distributed HIVSS in 6 clinic catchment areas. Follow-up to encourage confirmatory testing and antiretroviral therapy initiation was conducted through personal support (PS) or an automated short message service (SMS) follow-up and linkage system in 3 clinic areas each. Using a quasi-experimental pre-post design, we compared differences in the proportion of men testing in the clinic catchment areas during the HIVSS campaign (June-August 2019) to the 3 months prior (March-May 2019) and compared treatment initiations by assisted linkage strategy. RESULTS: Among 4793 participants accepting HIVSS, 62% had never tested. Among 3993 participants with follow-up data, 90.6% reported using their HIVSS kit. Testing coverage among men increased by 156%, from under 4% when only clinic-based HIV testing services were available to 9.5% when HIVSS and HIV testing services were available (z = -11.6; P < 0.01). Reported test use was higher for men followed through PS (99% vs. 68% in SMS); however, significantly more men reported reactive self-test results in the SMS group compared with PS (6.4% vs. 2.0%), resulting in more antiretroviral therapy initiations in the SMS group compared with PS (23 vs. 9; P < 0.01). CONCLUSIONS: CHW HIVSS distribution significantly increases testing among men. While PS enabled personalized follow-up, reporting differences indicate SMS is more acceptable and better aligned with expectations of privacy associated with HIVSS.

Navigating grey areas in HIV and mental health implementation science.

INTRODUCTION: Implementation science (IS) offers methods to systematically achieve the Ending the HIV Epidemic goals in the United States, as well as the global UNAIDS targets. Federal funders such as the National Institutes of Mental Health (NIMH) have invested in implementation research to achieve these goals, including supporting the AIDS Research Centres (ARCs), which focus on high-impact science in HIV and mental health (MH). To facilitate capacity building for the HIV/MH research workforce in IS, "grey areas," or areas of IS that are confusing, particularly for new investigators, should be addressed in the context of HIV/MH research. DISCUSSION: A group of IS experts affiliated with NIMH-funded ARCs convened to identify common and challenging grey areas. The group generated a preliminary list of 19 grey areas in HIV/MH-related IS. From the list, the authors developed a survey which was distributed to all ARCs to prioritize grey areas to address in this paper. ARC members across the United States (N = 60) identified priority grey areas requiring clarification. This commentary discusses topics with 40% or more endorsement. The top grey areas that ARC members identified were: (1) Differentiating implementation strategies from interventions; (2) Determining when an intervention has sufficient evidence for adaptation; (3) Integrating recipient perspectives into HIV/MH implementation research; (4) Evaluating whether an implementation strategy is evidence-based; (5) Identifying rigorous approaches for evaluating the impact of implementation strategies in the absence of a control group or randomization; and (6) Addressing innovation in HIV/MH IS grants. The commentary addresses each grey area by drawing from the existing literature (when available), providing expert guidance on addressing each in the context of HIV/MH research, and providing domestic and global HIV and HIV/MH case examples that address these grey areas. CONCLUSIONS: HIV/MH IS is key to achieving domestic and international goals for ending HIV transmission and mitigating its impact. Guidance offered in this paper can help to overcome challenges to rigorous and high-impact HIV/MH implementation research.

Neonatal neurobehavior associated with developmental changes from age 2 to 3 in very preterm infants.

OBJECTIVE: Understand how high-risk infants' development changes over time. Examine whether NICU Network Neurobehavioral Scale (NNNS) profiles are associated with decrements in developmental outcomes between ages 2 and 3 years in infants born very preterm. STUDY DESIGN: The Neonatal Outcomes for Very preterm Infants (NOVI) cohort is a multisite prospective study of 704 preterm infants born <30 weeks' gestation across nine university and VON affiliated NICUs. Data included infant neurobehavior measured by NNNS profiles at NICU discharge and the Bayley Scales of Infant and Toddler Development (BSID-III) at ages 2 and 3 years. Generalized estimating equations tested associations between NNNS profiles and BSID-III composite score changes between ages 2 and 3 years. RESULTS: The final study sample included 433 infants with mean gestational age of 27 weeks at birth. Infants with dysregulated NNNS profiles were more likely to have decreases in BSID-III Cognitive (OR = 2.66) and Language scores (OR = 2.53) from age 2 to 3 years compared to infants with more well-regulated neurobehavioral NNNS profiles. Further, infants with more well-regulated NNNS profiles were more likely to have increases in BSID-III Cognitive scores (OR = 2.03), rather than no change, compared to infants with dysregulated NNNS profiles. CONCLUSIONS AND RELEVANCE: Prior to NICU discharge, NNNS neurobehavioral profiles identified infants at increased risk for developing later language and cognitive challenges. Findings suggests that neonatal neurobehavior provides a unique, clinically significant contribution to the evaluation of very preterm infants to inform treatment planning for the most vulnerable.

Exploring the prognostic significance of arm-level copy number alterations in triple-negative breast cancer.

Somatic copy number alterations (SCNAs) are prevalent in cancer and play a significant role in both tumorigenesis and therapeutic resistance. While focal SCNAs have been extensively studied, the impact of larger arm-level SCNAs remains poorly understood. Here, we investigated the association between arm-level SCNAs and overall survival in triple-negative breast cancer (TNBC), an aggressive subtype of breast cancer lacking targeted therapies. We identified frequent arm-level SCNAs, including 21q gain and 7p gain, which correlated with poor overall survival in TNBC patients. Further, we identified the expression of specific genes within these SCNAs associated with survival. Notably, we found that the expression of RIPK4, a gene located on 21q, exhibited a strong correlation with poor overall survival. In functional assays, we demonstrated that targeting Ripk4 in a murine lung metastatic TNBC model significantly reduced tumor burden, improved survival, and increased CD4+ and CD8+ T cell infiltration. RIPK4 enhanced the survival of triple-negative breast cancer cells at secondary sites, thereby facilitating the formation of metastatic lesions. Our findings highlight the significance of arm-level SCNAs in breast cancer progression and identify RIPK4 as a putative driver of TNBC metastasis and immunosuppression.

Correlation between gender-based violence and poor treatment outcomes among transgender women living with HIV in Brazil.

BACKGROUND: Transgender women are disproportionately affected by both HIV and gender-based violence (GBV), defined as physical, sexual, or emotional violence perpetrated against an individual based on their gender identity/expression. While a growing body of evidence demonstrates that GBV leads to poor HIV care and treatment outcomes among cisgender women, less research has examined this association among transgender women. We assessed the impact of lifetime experiences of GBV on subsequent retention in HIV care and laboratory confirmed viral suppression among a sample of transgender women living with HIV (TWH) in Brazil. METHODS: A pilot trial of a peer navigation intervention to improve HIV care and treatment among TWH was conducted in São Paulo, Brazil between 2018 and 2019. TWH were recruited and randomized into the intervention or control arm and participated in a baseline and 9-month follow-up survey and ongoing extraction of clinical visit, prescribing, and laboratory data. Generalized linear model regressions with a Poisson distribution estimated the relative risk (RR) for the association of lifetime physical and sexual violence reported at baseline with treatment outcomes (retention in HIV care and viral suppression) at follow-up, adjusting for baseline sociodemographic characteristics. RESULTS: A total of 113 TWH participated in the study. At baseline, median age was 30 years, and the prevalence of lifetime physical and sexual violence was 62% and 45%, respectively. At follow-up, 58% (n = 66/113) were retained in care and 35% (n = 40/113) had evidence of viral suppression. In adjusted models, lifetime physical violence was non-significantly associated with a 10% reduction in retention in care (aRR: 0.90, 95% CI: 0.67, 1.22) and a 31% reduction in viral suppression (aRR: 0.69; 95% CI: 0.43, 1.11). Lifetime sexual violence was non-significantly associated with a 28% reduction in retention in HIV care (aRR: 0.72, 95% CI: 0.52, 1.00) and significantly associated with a 56% reduction in viral suppression (aRR: 0.44; 95% CI: 0.24, 0.79). CONCLUSION: Our findings are among the first to demonstrate that lifetime experiences with physical and sexual violence are associated with poor HIV outcomes over time among transgender women. Interventions seeking to improve HIV treatment outcomes should assess and address experiences of GBV among this population. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03525340.

Epigenetic associations in HPA axis genes related to bronchopulmonary dysplasia and antenatal steroids.

BACKGROUND: Bronchopulmonary dysplasia (BPD), a common morbidity among very preterm infants, is associated with chronic disease and neurodevelopmental impairments. A hypothesized mechanism for these outcomes lies in altered glucocorticoid (GC) activity. We hypothesized that BPD and its treatments may result in epigenetic differences in the hypothalamic-pituitary-adrenal (HPA) axis, which is modulated by GC, and could be ascertained using an established GC risk score and DNA methylation (DNAm) of HPA axis genes. METHODS: DNAm was quantified from buccal tissue (ECHO-NOVI) and from neonatal blood spots (ELGAN ECHO) via the EPIC microarray. Prenatal maternal characteristics, pregnancy complication, and neonatal medical complication data were collected from medical record review and maternal interviews. RESULTS: The GC score was not associated with steroid exposure or BPD. However, six HPA genes involved in stress response regulation demonstrated differential methylation with antenatal steroid exposure; two CpGs within FKBP5 and POMC were differentially methylated with BPD severity. These findings were sex-specific in both cohorts; males had greater magnitude of differential methylation within these genes. CONCLUSIONS: These findings suggest that BPD severity and antenatal steroids are associated with DNAm at some HPA genes in very preterm infants and the effects appear to be sex-, tissue-, and age-specific. IMPACT: This study addresses bronchopulmonary dysplasia (BPD), an important health outcome among preterm neonates, and interrogates a commonly studied pathway, the hypothalamic-pituitary-adrenal (HPA) axis. The combination of BPD, the HPA axis, and epigenetic markers has not been previously reported. In this study, we found that BPD itself was not associated with epigenetic responses in the HPA axis in infants born very preterm; however, antenatal treatment with steroids was associated with epigenetic responses.

Cost Analysis of Short Messaging Service and Peer Navigator Interventions for Linking and Retaining Adults Recently Diagnosed With HIV in Care in South Africa.

INTRODUCTION: Large proportions of people living with HIV (PLHIV) in sub-Saharan Africa are not linked to or retained in HIV care. There is a critical need for cost-effective interventions to improve engagement and retention in care and inform optimal allocation of resources. METHODS: We estimated costs associated with a short message service (SMS) plus peer navigation (SMS+PN) intervention; an SMS-only intervention; and standard of care (SOC), within the I-Care cluster-randomized trial to improve HIV care engagement for recently diagnosed PLHIV. We employed a uniform cost data-collection protocol to quantify resources used and associated costs for each intervention. RESULTS: Compared with SOC, the SMS+PN intervention cost $1284 ($828-$2859) more per additional patient linked to care within 30 days and $1904 ($1158-$5343) more per additional patient retained in care at 12 months, while improving linkage by 24% (95% CI: 11 to 36) and retention by 16% (95% CI: 6 to 26). By contrast, the SMS-only intervention cost $198 ($93-dominated) more per additional patient linked to care and $697 ($171-dominated) more per additional patient retained in care but was not significantly associated with improvements in linkage (12%; 95% CI: -1 to 25) or retention (3%; 95% CI: -7 to 14) compared with SOC. The efficiency of the SMS+PN intervention could be improved by 46%, to $690 more per additional patient linked and $1023 more per additional patient retained in care, if implemented within the Department of Health using more efficient distribution of staff resources. DISCUSSION: Findings suggest that scale-up of the SMS+PN intervention could benefit patients, improving care and health outcomes while being cost-effective.

Contributions of prenatal risk factors and neonatal epigenetics to cognitive outcome in children born very preterm.

Children born less than 30 weeks gestational age (GA) are at high risk for neurodevelopmental delay compared to term peers. Prenatal risk factors and neonatal epigenetics could help identify preterm children at highest risk for poor cognitive outcomes. We aimed to understand the associations among cumulative prenatal risk, neonatal DNA methylation, and child cognitive ability at age 3 years, including whether DNA methylation mediates the association between prenatal risk and cognitive ability. We studied 379 neonates (54% male) born less than 30 weeks GA who had DNA methylation measured at neonatal intensive care unit discharge along with 3-year follow-up data. Cumulative prenatal risk was calculated from 24 risk factors obtained from maternal report and medical record and epigenome-wide neonatal DNA methylation was assayed from buccal swabs. At 3-year follow-up, child cognitive ability was assessed using the Bayley Scales of Infant and Toddler Development (third edition). Cumulative prenatal risk and DNA methylation at two cytosine-phosphate-guanines (CpGs) were uniquely associated with child cognitive ability. Using high-dimensional mediation analysis, we also identified differential methylation of 309 CpGs that mediated the association between cumulative prenatal risk and child cognitive ability. Many of the associated CpGs were located in genes (TNS3, TRAPPC4, MAD1L1, APBB2, DIP2C, TRAPPC9, DRD2) that have previously been associated with prenatal exposures and/or neurodevelopmental phenotypes. Our findings suggest a role for both prenatal risk factors and DNA methylation in explaining outcomes for children born preterm and suggest we should further study DNA methylation as a potential mechanism underlying the association between prenatal risk and child neurodevelopment. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Compelling evidence from meta-epidemiological studies demonstrates overestimation of effects in randomized trials that fail to optimize randomization and blind patients and outcome assessors.

OBJECTIVES: To investigate the impact of potential risk of bias elements on effect estimates in randomized trials. STUDY DESIGN AND SETTING: We conducted a systematic survey of meta-epidemiological studies examining the influence of potential risk of bias elements on effect estimates in randomized trials. We included only meta-epidemiological studies that either preserved the clustering of trials within meta-analyses (compared effect estimates between trials with and without the potential risk of bias element within each meta-analysis, then combined across meta-analyses; between-trial comparisons), or preserved the clustering of substudies within trials (compared effect estimates between substudies with and without the element, then combined across trials; within-trial comparisons). Separately for studies based on between- and within-trial comparisons, we extracted ratios of odds ratios (RORs) from each study and combined them using a random-effects model. We made overall inferences and assessed certainty of evidence based on Grading of Recommendations, Assessment, development, and Evaluation and Instrument to assess the Credibility of Effect Modification Analyses. RESULTS: Forty-one meta-epidemiological studies (34 of between-, 7 of within-trial comparisons) proved eligible. Inadequate random sequence generation (ROR 0.94, 95% confidence interval [CI] 0.90-0.97) and allocation concealment (ROR 0.92, 95% CI 0.88-0.97) probably lead to effect overestimation (moderate certainty). Lack of patients blinding probably overestimates effects for patient-reported outcomes (ROR 0.36, 95% CI 0.28-0.48; moderate certainty). Lack of blinding of outcome assessors results in effect overestimation for subjective outcomes (ROR 0.69, 95% CI 0.51-0.93; high certainty). The impact of patients or outcome assessors blinding on other outcomes, and the impact of blinding of health-care providers, data collectors, or data analysts, remain uncertain. Trials stopped early for benefit probably overestimate effects (moderate certainty). Trials with imbalanced cointerventions may overestimate effects, while trials with missing outcome data may underestimate effects (low certainty). Influence of baseline imbalance, compliance, selective reporting, and intention-to-treat analysis remain uncertain. CONCLUSION: Failure to ensure random sequence generation or adequate allocation concealment probably results in modest overestimates of effects. Lack of patients blinding probably leads to substantial overestimates of effects for patient-reported outcomes. Lack of blinding of outcome assessors results in substantial effect overestimation for subjective outcomes. For other elements, though evidence for consistent systematic overestimate of effect remains limited, failure to implement these safeguards may still introduce important bias.

Anticipated Stigma and Social Barriers to Communication Between Transgender Women Newly Diagnosed with HIV and Health Care Providers: A Mediation Analysis.

Purpose: We assessed whether anticipated stigma (i.e., fear of public mistreatment due to gender identity) impacts communication between transgender women (TGW) living with HIV and health care providers. Methods: This is a secondary analysis of baseline data from Trans Amigas, a study conducted in Brazil, 2018. The study population consisted of TGW living with HIV, older than 18 years, residing in the São Paulo metropolitan area. We used multivariable logistic regression (α = 0.05), mediation, and bootstrapping for the analysis. Results: One hundred and thirteen participants completed the study. Fear of public mistreatment had an adjusted odds ratio (aOR) of 7.42 (p = 0.003) for difficulty reporting new symptoms to providers. Concerning fear of public mistreatment, we found that unemployment had an aOR of 3.62 (p = 0.036); sex work, an aOR of 2.95 (p = 0.041); and issues related to name change in documents, an aOR of 2.71 (p = 0.033). For the indirect effect on difficulty reporting new symptoms, mediated by fear of public mistreatment, unemployment had an aOR of 1.52 (confidence interval [CI] = 0.88-2.24); sex work, an aOR of 1.48 (CI = 0.81-2.52); and name change issues, an aOR of 1.47 (CI = 0.96-2.43). Conclusions: Anticipated stigma was associated with communication difficulties between TGW living with HIV and providers. Our data suggest that structural factors associated with anticipated stigma could indirectly impact on difficulty reporting new symptoms. These findings indicate the importance of considering social contexts that intersect with individual experiences when analyzing communication barriers between providers and patients, and the need to strengthen social policies for TGW in Brazil. Clinical Trial Registration number: R34MH112177.

Agreement Between Two Behavioral Rating Scales in Preschoolers Born Very Preterm.

OBJECTIVE: Broadband parent rating scales are commonly used to assess behavioral problems in children. Multiple rating scales are available, yet agreement between them is not well-understood. The objective of this study was to evaluate agreement between the Behavior Assessment System for Children, Third Edition (BASC-3), and Child Behavior Checklist 1.5 to 5 years (CBCL) in a sample of children born very preterm. METHOD: We assessed 73 children born < 30 weeks' gestational age whose caregivers completed the BASC-3 and CBCL at age 4. We examined correlations, within-person differences, and agreement in clinical categorization for all corresponding subscales and composites. RESULTS: Comparable subscales on the BASC-3 and CBCL were significantly correlated, albeit to differing magnitudes. Subscales indexing hyperactivity and attention problems were the most comparable across the 2 measures, evidenced by strong correlations and few to no differences in mean T-scores. Composite scores indexing internalizing, externalizing, and total problems were also strongly correlated, and there were no differences in the mean T-scores for externalizing or total problems across measures. Agreement in clinical classifications were weak to moderate, though again, the highest agreement was found for hyperactivity, attention, externalizing, and total problems. CONCLUSION: Agreement between BASC-3 and CBCL subscales was weak to moderate, with the exception of subscales related to attention and hyperactivity, as well as composite scores indicating overall behavior problems. Researchers and clinicians should consider these discrepancies when interpreting the results of behavior rating scales with preschool children because conclusions could differ based on the assessment that is used.

Two-Year Autism Risk Screening and 3-Year Developmental Outcomes in Very Preterm Infants.

Importance: Use of the Modified Checklist for Autism in Toddlers, Revised With Follow-Up, a 2-stage parent-report autism risk screening tool, has been questioned due to reports of poor sensitivity and specificity. How this measure captures developmental delays for very preterm infants may provide support for continued use in pediatric care settings. Objective: To determine whether autism risk screening with the 2-stage parent-report autism risk screening tool at age 2 years is associated with behavioral and developmental outcomes at age 3 in very preterm infants. Design, Setting, and Participants: Neonatal Neurobehavior and Outcomes for Very Preterm Infants was a longitudinal, multisite cohort study. Enrollment occurred April 2014 to June 2016, and analyses were conducted from November 2022 to May 2023. Data were collected across 9 university-affiliated neonatal intensive care units (NICUs). Inclusion criteria were infants born less than 30 weeks' gestational age, a parent who could read and speak English and/or Spanish, and residence within 3 hours of the NICU and follow-up clinic. Exposures: Prematurity and use of the 2-stage parent-report autism risk screening tool at age 2 years. Main Outcomes and Measures: Outcomes include cognitive, language, motor composites on Bayley Scales for Infant and Toddler Development, third edition (Bayley-III) and internalizing, externalizing, total problems, and pervasive developmental disorder (PDD) subscale on the Child Behavior Checklist (CBCL) at age 3 years. Generalized estimating equations tested associations between the 2-stage parent-report autism risk screening tool and outcomes, adjusting for covariates. Results: A total of 467 children (mean [SD] gestational age, 27.1 [1.8] weeks; 243 male [52%]) were screened with the 2-stage parent-report autism risk screening tool at age 2 years, and outcome data at age 3 years were included in analyses. Mean (SD) maternal age at birth was 29 (6) years. A total of 51 children (10.9%) screened positive on the 2-stage parent-report autism risk screening tool at age 2 years. Children with positive screening results were more likely to have Bayley-III composites of 84 or less on cognitive (adjusted odds ratio [aOR], 4.03; 95% CI, 1.65-9.81), language (aOR, 5.38; 95% CI, 2.43-11.93), and motor (aOR, 4.74; 95% CI, 2.19-10.25) composites and more likely to have CBCL scores of 64 or higher on internalizing (aOR, 4.83; 95% CI, 1.88-12.44), externalizing (aOR, 2.69; 95% CI, 1.09-6.61), and PDD (aOR, 3.77; 95% CI, 1.72-8.28) scales. Conclusions and Relevance: Results suggest that the 2-stage parent-report autism risk screening tool administered at age 2 years was a meaningful screen for developmental delays in very preterm infants, with serious delays detected at age 3 years.

Epigenetic age acceleration, neonatal morbidities, and neurobehavioral profiles in infants born very preterm.

Epigenetic age acceleration is a risk factor for chronic diseases of ageing and may reflect aspects of biological ageing. However, few studies have examined epigenetic ageing during the early neonatal period in preterm infants, who are at heightened risk of developmental problems. We examined relationships between neonatal age acceleration, neonatal morbidities, and neurobehavioral domains among very preterm (<30 weeks gestation) infants to characterize whether infants with early morbidities or different neurobehavioral characteristics had accelerated or decelerated epigenetic ageing. This study uses data from the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) study, restricted to infants with data on variables assessed (n = 519). We used generalized estimating equations to test for differences in age acceleration associated with severe neonatal medical morbidities and neurobehavioral characteristics. We found that infants with neonatal morbidities, in particular, bronchopulmonary dysplasia (BPD), had accelerated epigenetic age - and some evidence that infants with hypertonicity and asymmetric reflexes had increased and decreased age acceleration, respectively. Adjustment for gestational age attenuated some associations, suggesting that the relationships observed may be driven by the duration of gestation. Our most robust finding shows that very preterm infants with neonatal morbidities (BPD in particular) exhibit age acceleration, but most neonatal neurobehavioral characteristics and morbidities are not associated with early life age acceleration. Lower gestational age at birth may be an upstream factor driving these associations.

A guaranteed income intervention to improve the health and financial well-being of low-income black emerging adults: study protocol for the Black Economic Equity Movement randomized controlled crossover trial.

Background: Economic inequity systematically affects Black emerging adults (BEA), aged 18-24, and their healthy trajectory into adulthood. Guaranteed income (GI)-temporary, unconditional cash payments-is gaining traction as a policy solution to address the inequitable distribution of resources sewn by decades of structural racism and disinvestment. GI provides recipients with security, time, and support to enable their transition into adulthood and shows promise for improving mental and physical health outcomes. To date, few GI pilots have targeted emerging adults. The BEEM trial seeks to determine whether providing GI to BEA improves financial wellbeing, mental and physical health as a means to address health disparities. Methods/design: Using a randomized controlled crossover trial design, 300 low-income BEA from San Francisco and Oakland, California, are randomized to receive a $500/month GI either during the first 12-months of follow-up (Phase I) or during the second 12-months of a total of 24-months follow-up (Phase II). All participants are offered enrollment in optional peer discussion groups and financial mentoring to bolster financial capability. Primary intention-to-treat analyzes will evaluate the impact of GI at 12 months among Phase I GI recipients compared to waitlist arm participants using Generalized Estimating Equations (GEE). Primary outcomes include: (a) financial well-being (investing in education/training); (b) mental health status (depressive symptoms); and (c) unmet need for mental health and sexual and reproductive health services. Secondary analyzes will examine effects of optional financial capability components using GEE with causal inference methods to adjust for differences across sub-strata. We will also explore the degree to which GI impacts dissipate after payments end. Study outcomes will be collected via surveys every 3 months throughout the study. A nested longitudinal qualitative cohort of 36 participants will further clarify how GI impacts these outcomes. We also discuss how anti-racism praxis guided the intervention design, evaluation design, and implementation. Discussion: Findings will provide the first experimental evidence of whether targeted GI paired with complementary financial programming improves the financial well-being, mental health, and unmet health service needs of urban BEA. Results will contribute timely evidence for utilizing GI as a policy tool to reduce health disparities. Clinical trial registration: https://clinicaltrials.gov, identifier NCT05609188.

Understanding the effects of universal test and treat on longitudinal HIV care outcomes among South African youth: a retrospective cohort study.

INTRODUCTION: Little is known about the effects of universal test and treat (UTT) policies on HIV care outcomes among youth living with HIV (YLHIV). Moreover, there is a paucity of information regarding when YLHIV are most susceptible to disengagement from care under the newest treatment guidelines. The longitudinal HIV care continuum is an underutilized tool that can provide a holistic understanding of population-level HIV care trajectories and be used to compare treatment outcomes across groups. We aimed to explore effects of the UTT policy on longitudinal outcomes among South African YLHIV and identify temporally precise opportunities for re-engaging this priority population in the UTT era. METHODS: Using medical record data, we conducted a retrospective cohort study among youth aged 18-24 diagnosed with HIV from August 2015-December 2018 in nine health care facilities in South Africa. We used Fine and Gray sub-distribution proportional hazards models to characterize longitudinal care continuum outcomes in the population overall and stratified by treatment era of diagnosis. We estimated the proportion of individuals in each stage of the continuum over time and the restricted mean time spent in each stage in the first year following diagnosis. Sub-group estimates were compared using differences. RESULTS: A total of 420 YLHIV were included. By day 365 following diagnosis, just 23% of individuals had no 90-or-more-day lapse in care and were virally suppressed. Those diagnosed in the UTT era spent less time as ART-naïve (mean difference=-19.3 days; 95% CI: -27.7, -10.9) and more time virally suppressed (mean difference = 17.7; 95% CI: 1.0, 34.4) compared to those diagnosed pre-UTT. Most individuals who were diagnosed in the UTT era and experienced a 90-or-more-day lapse in care disengaged between diagnosis and linkage to care or ART initiation and viral suppression. CONCLUSIONS: Implementation of UTT yielded modest improvements in time spent on ART and virally suppressed among South African YLHIV- however, meeting UNAIDS' 95-95-95 targets remains a challenge. Retention in care and re-engagement interventions that can be implemented between diagnosis and linkage to care and between ART initiation and viral suppression (e.g., longitudinal counseling) may be particularly important to improving care outcomes among South African YLHIV in the UTT era.