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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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.

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.

Epigenetic associations with neonatal age in infants born very preterm, particularly among genes involved in neurodevelopment.

The time from conception through the first year of life is the most dynamic period in human development. This time period is particularly important for infants born very preterm (< 30 weeks gestation; VPT), as they experience a significant disruption in the normal developmental trajectories and are at heightened risk of experiencing developmental impairments and delays. Variations in the epigenetic landscape during this period may reflect this disruption and shed light on the interrelationships between aging, maturation, and the epigenome. We evaluated how gestational age (GA) and age since conception in neonates [post-menstrual age (PMA)], were related to DNA methylation in buccal cells collected at NICU discharge from VPT infants (n = 538). After adjusting for confounders and applying Bonferroni correction, we identified 2,366 individual CpGs associated with GA and 14,979 individual CpGs associated with PMA, as well as multiple differentially methylated regions. Pathway enrichment analysis identified pathways involved in axonogenesis and regulation of neuron projection development, among many other growth and developmental pathways (FDR q < 0.001). Our findings align with prior work, and also identify numerous novel associations, suggesting that genes important in growth and development, particularly neurodevelopment, are subject to substantial epigenetic changes during early development among children born VPT.

Fatores associados à retenção de travestis e mulheres trans vivendo com HIV em uma intervenção com navegação de pares em São Paulo, Brasil / Factores asociados con la retención de travestis y mujeres transgénero que viven con el VIH en una intervención consultada por pares en São Paulo, Brasil / Factors associated with the retention of travestis and transgender women living with HIV in a peer navigation intervention in São Paulo, Brazil

Travestis e mulheres trans (TrMT) pertencem aos grupos com mais alta prevalência do HIV no mundo, com maior probabilidade de infecção em relação à população geral e menor adesão a estratégias de prevenção e tratamento do que outros grupos vulneráveis. Considerando esses desafios, descrevemos os fatores associados à retenção de TrMT com HIV no projeto TransAmigas. O recrutamento ocorreu entre abril de 2018 e setembro de 2019, em um serviço público de saúde em São Paulo, Brasil. Foram inscritas 113 TrMT, atribuídas aleatoriamente para uma intervenção com navegadora de pares (75) ou um grupo controle (38) e seguidas durante nove meses. Para analisar a associação entre as variáveis selecionadas e o desfecho ("retenção aos nove meses" independentemente do contato aos três meses, definido pela "resposta completa ao questionário final"), foram empregados modelos de regressão logística bi e multivariados. Uma exploração qualitativa dos formulários de contato de pares foi realizada para validar e complementar a seleção prévia de variáveis do componente quantitativo. Das 113 participantes, 79 (69,9%) responderam à entrevista de nove meses, sendo 54 (72%) do grupo intervenção e 25 (66%) do grupo controle. No modelo multivariado final, o contato aos três meses (odds ratio ajustado - ORa = 6,15; intervalo de 95% de confiança - 95%CI: 2,16-17,51) e a maior escolaridade (≥ 12 anos) (ORa = 3,26; IC95%: 1,02-10,42) permaneceram associados ao desfecho, ajustados por raça/cor, idade < 35 anos e revelação do status sorológico para HIV. Pesquisas futuras com TrMT devem incluir contato em intervalos regulares, com esforços adicionais voltados a participantes com menor escolaridade.

La población de travestis y mujeres trans (TrMT) está en los grupos con mayor prevalencia de VIH en el mundo, con mayor probabilidad de infección en comparación con la población general y menor adherencia a las estrategias de prevención y tratamiento que otros grupos vulnerables. Ante estos desafíos, describimos los factores asociados a la retención de TrMT con VIH en el proyecto TransAmigas. La selección ocurrió entre abril de 2018 y septiembre de 2019, en un servicio público de salud de São Paulo, Brasil. Se inscribieron 113 TrMT, a las cuales se asignaron aleatoriamente a una intervención de navegador de pares (75) o a un grupo control (38) y se les dio seguimiento durante 9 meses. Para analizar la asociación entre las variables seleccionadas y el resultado ("retención a los nueve meses" independientemente del contacto a los 3 meses, definido por "respuesta completa al cuestionario final"), se utilizaron modelos de regresión logística bi- y multivariante. Se realizó una exploración cualitativa de los formularios de contacto de pares para validar y complementar la selección previa de las variables en el componente cuantitativo. De las 113 participantes, 79 (69,9%) respondieron a la entrevista de los 9 meses, de las cuales 54 (72%) pertenecían al grupo intervención y 25 (66%) al grupo control. En el modelo multivariante final, el contacto a los 3 meses (odds ratio ajustado - ORa = 6,15; intervalo de 95% de confianza - IC95%: 2,16-17,51) y un alto nivel de instrucción (≥ 12 años) (ORa = 3,26; IC95%: 1,02-10,42) permanecieron asociados con el resultado, ajustado por etnia/color, edad < 35 años y divulgación del estado serológico respecto al VIH. Los futuros estudios con la población TrMT deberán incluir contacto a intervalos regulares, con esfuerzos adicionales dirigidos a las participantes con menor nivel de instrucción.

Travestis and transgender women (TrTGW) constitute the groups with the highest HIV prevalence in the world, with higher probability of infection compared with the general population and lower adherence to prevention and treatment strategies than other vulnerable groups. Considering these challenges, this study describes the factors associated with the retention of TrTGW with HIV to the TransAmigas project. Participants were recruited from April 2018 to September 2019 in a public health service in São Paulo, Brazil. A total of 113 TrTGW were randomly assigned to either a peer navigation intervention (75) or a control group (38) and followed up for nine months. To analyze the association between the selected variables and the outcome ("retention at nine months", regardless of contact at three months, defined by the "full completion of the final questionnaire"), bivariate and multivariate logistic regression models were used. Peer contact forms were qualitatively assessed to validate and complement the previous selection of quantitative component variables. Of the 113 participants, 79 (69.9%) participated in the interview after nine months, of which 54 (72%) were from the intervention group and 25 (66%) from the control group. In the final multivariate model, contact at three months (adjusted odds ratio - aOR = 6.15; 95% confidence interval - 95%CI: 2.16-17.51) and higher schooling level (≥ 12 years) (aOR = 3.26; 95%CI: 1.02-10.42) remained associated with the outcome, adjusted by race/skin color, age ≤ 35 years, and HIV serostatus disclosure. Future studies with TrTGW should include contact at regular intervals, with additional efforts aimed at participants with lower schooling level.

Over-the-counter human immunodeficiency virus self-test kits: time to explore their use for men who have sex with men in Brazil

Increasing access and frequency of human immunodeficiency virus testing are critical to stemming the epidemic. In Brazil's concentrated epidemic, human immunodeficiency virus prevalence in the men who have sex with men/transgender population far exceeds that in the general population, but testing rates fall below what is needed to ensure early detection and treatment. Over-the-counter human immunodeficiency virus self-testing kits, now available in stores in the U.S., have enormous potential to increase testing access and frequency and to facilitate early detection and treatment. With the advent of human immunodeficiency virus self-testing upon us, it is timely to engage the scientific community, government, and civil society in a dialog around how to best utilize this technology in Brazil. We summarize recent research on over-the-counter testing among men who have sex with men, raise potential questions and challenges to using self-tests, suggest implementation strategies, and outline a research agenda moving forward.

Acceptability of self-conducted home-based HIV testing among men who have sex with men in Brazil: data from an on-line survey / Aceitabilidade da autotestagem domiciliar para o HIV entre homens que fazem sexo com homens no Brasil: dados de uma enquete na Internet / Aceptabilidad del examen de VIH autoadministrado en casa con hombres que practican sexo con hombres en Brasil: datos de una encuesta por internet

The Brazilian HIV/AIDS epidemic is concentrated among men who have sex with men (MSM), however HIV testing rates among MSM are not commensurate with their risk. Strategies to expand early diagnosis may include use of self-conducted home-based testing kits, which are now available for purchase in the US. In April 2011 we conducted a survey with Brazilian MSM using Facebook to assess HIV testing preferences and acceptability of home-based testing. Among 356 previously tested, HIV-negative MSM, 47% reported a preference for home-based testing, 27% preferred clinic-based testing, and 26% had no preference. Less frequent testers and those who had considered testing but failed to test were more likely to prefer home-based testing. Close to 90% reported that they would use self-test kits; 62% and 54% said they would use home-based testing to make choices about unprotected sex with regular and new partners, respectively. Concerns included difficulty to understand the tests (32%) and receiving results alone (23%). Overall, home-based testing may appeal to MSM and result in increased testing frequency. Research on feasibility and utilization of self-tests in practice is needed.

A epidemia de HIV/AIDS no Brasil é concentrada em homens que fazem sexo com homens (HSH), mas suas taxas de testagem são incompatíveis com seus riscos. Estratégias para expandir o diagnóstico precoce entre HSH podem incluir kits de autotestagem em ambiente doméstico (AAD), como os disponíveis para compra nos Estados Unidos. Em abril de 2011, realizamos uma pesquisa com HSH brasileiros recrutados em Facebook para conhecer preferências de testagem e aceitabilidade da AAD. Entre 356 HSH HIV(-) testados previamente, 47% preferiam a AAD, 27% testagem em clínicas e 26% sem preferência. HSH com menos testagem ou que consideraram a testagem sem fazê-la tinham maior probabilidade de preferir a AAD (p < 0,05). Quase 90% usariam a AAD, 62 e 54% para decidir sobre ter sexo desprotegido com parceiros regulares e novos, respectivamente. Dificuldade de entender os testes (32%) e receber os resultados sozinhos (23%) foram preocupações referidas. Testes anti-HIV de AAD podem ser atrativos para HSH e resultar em aumento de testagem. Pesquisas com foco na viabilidade e utilização dos kits AAD na prática são necessárias.

La epidemia de VIH/SIDA en Brasil se concentra en hombres que practican sexo con hombres (HSH), pero los índices de exámenes clínicos para conocer si están infectados son incompatibles con sus riesgos. Las estrategias para expandir el diagnóstico precoz entre HSH pueden incluir kits de autoanálisis para el hogar, como los que están a disposición del público en Estados Unidos. En abril de 2011, realizamos una investigación con HSH brasileños, captados en Facebook, para conocer preferencias de exámenes y la aceptabilidad del autoanálisis en un ambiente doméstico. Entre los 356 HSH VIH(-) analizados previamente, un 47% preferían un autoanálisis en un ambiente doméstico, un 27% pruebas en clínicas y un 26% no tenían preferencias. HSH que menos exámenes se realizaron o quienes los consideraron, pero no se los hicieron, tenían mayor probabilidad de preferir el autoanálisis en un ambiente doméstico. Casi un 90% usarían autoanálisis en su hogar, un 62% y 54% con el fin de decidir sobre tener sexo sin protección con parejas regulares y nuevas, respectivamente. La dificultad de entender los análisis (32%) y recibir los resultados a solas (23%) fueron las preocupaciones a las que se refirieron. Los análisis anti-VIH de autoadministración en el hogar pueden ser atractivos para HSH y resultar en un aumento de exámenes. Las investigaciones centradas en la viabilidad y utilización de los test de autoanálisis en la práctica son necesarias.

Diagnóstico precoce e os fatores associados às infecções sexualmente transmissíveis em mulheres atendidas na atenção primária / Early diagnosis and correlations of sexually transmitted infections among women in primary care health services

INTRODUÇÃO: Infecções Sexualmente Transmissíveis (IST) em mulheres permanecem um desafio para a Saúde Pública: elevada prevalência, dificuldade para implantação de estratégias de diagnóstico precoce e elevada ocorrência de sequelas. OBJETIVO: Identificar a prevalência de IST em usuárias de um serviço de atenção primária à saúde em São Paulo. MÉTODOS: Mulheres de 18 a 40 anos foram convidadas para realizar autocoleta de secreção vaginal para a detecção de Chlamydia trachomatis, Neisseria gonorrhoeae e Trichomonas vaginalis por meio de Reacão em Cadeia da Polimerase (PCR). As mulheres também responderam a um questionário com questões demográficas e relativas à história sexual face a face ou autoaplicado por meio de um computador. RESULTADOS: Das 781 mulheres incluídas no estudo, as prevalências obtidas foram: Chlamydia trachomatis (8,4 por cento), Neisseria gonorrhoeae (1,9 por cento) e Trichomonas vaginalis (3,2 por cento). A positividade para pelo menos uma das três IST foi de 13 por cento. As variáveis associadas independentemente com maior risco de IST foram: idade menor que 20 anos, mais de dois parceiros sexuais na vida e percepção de risco para IST; o uso de preservativo como método contraceptivo foi um fator protetor. CONCLUSÃO: A prevalência encontrada em usuárias indica a necessidade da implantação de estratégias de rastreamento de IST em serviços de atenção primária.

INTRODUCTION: Sexually Transmitted Infections (STIs) in women remain a public health challenge due to high prevalence, difficulties to implement early diagnosis strategies and high rates of complications. OBJECTIVE: Identify the prevalence of STIs among users of a primary health care clinic in São Paulo. METHODS: Women, 18 to 40 years of age, were invited to self-collect vaginal specimens to be tested for Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis by Polymerase Chain Reaction (PCR). Women were also invited to answer a demographic and sexual history questionnaire, either on the computer or face-to-face. RESULTS: The prevalence of STIs obtained from the 781 women included in the study was: Chlamydia trachomatis: 8.4 percent, Neisseria gonorrhoeae: 1.9 percent, and Trichomonas vaginalis: 3.2 percent. Thirteen percent tested positive for at least one out of the three STIs. The variables associated independently with a higher risk of STIs were: age under 20-years-old, more than two lifetime sexual partners, and self-perception of STI risk. The use of condoms as a contraceptive method proved to be a protective factor. CONCLUSION: The high prevalence found among these women indicates the need for the implementation of STI screening strategies in primary care settings in Brazil.