Faculty Bibliography

INTRODUCTION/BACKGROUND:Effective July 2018, the U.S. Department of Housing and Urban Development issued a rule requiring all public housing authorities to implement smoke-free housing (SFH) policies in their developments. We examined the differential impacts of SFH policy on hospitalizations for myocardial infarction (MI) and stroke among adults aged ≥50 years old living in New York City (NYC) Housing Authority (NYCHA) versus a matched-comparison population in NYC. AIMS AND METHODS/OBJECTIVE:We identified census block groups (CBGs) comprised solely of 100% NYCHA units (N = 160) and compared NYCHA CBGs to a selected subset of CBGs from all CBGs with no NYCHA units (N = 5646). We employed propensity score matching on distributions of key CBG-level sociodemographic and housing covariates. We constructed incident rates per 1000 persons by aggregating 3-month "quarterly" counts of New York State all-payer hospitalization data from October 2015 to December 2022 and dividing by the population aged ≥50 in selected CBGs, ascertained from 2016 American Community Survey 5-year estimates. We selected a difference-in-differences (DID) analytic approach to examine pre- and post-policy differences in incident hospitalizations between the intervention and matched-comparison groups. RESULTS:Matching results indicated a balanced match for all covariates, with standardized mean differences <0.10. In DID analyses, we observed small declines in both MI (DID = -0.26, p = .02) and stroke (DID = -0.28, p = .06) hospitalization rates for NYCHA CBGs compared to non-NYCHA CBGs from pre-to post-54 months' policy. CONCLUSIONS:SFH policies in NYC were associated with small reductions in CVD-related hospitalizations among older adults living in housing subject to the policy. IMPLICATIONS/CONCLUSIONS:Housing remains a key focal setting for interventions to reduce SHS exposure and associated morbidities. Ongoing monitoring is warranted to understand the long-term impacts of SFH policies in public housing developments.

INTRODUCTION/BACKGROUND:Expanding access to medication for opioid use disorder (MOUD) to people involved in the carceral system is a priority for the New Hampshire Department of Corrections (NHDOC), where more than 40% of residents have an opioid use disorder (OUD). NHDOC participated in the multi-site Justice Community Opioid Innovation Network (JCOIN) clinical trial, "Long-acting buprenorphine vs. naltrexone opioid treatments in criminal justice system-involved adults (EXIT-CJS)". We examine the contributing factors to the expansion of the NHDOC MOUD program from 2021 to 2023, including participation in EXIT-CJS, which occurred from 2019 to 2024. METHODS:Data on quarterly MOUD prescribing and EXIT-CJS enrollments were abstracted from the NHDOC medical records from July 1, 2021- December 31, 2023 as part of a quality improvement initiative. To examine factors influencing expansion of the program, conversations were conducted with NHDOC leadership team and clinical staff. RESULTS:From 2021 to 2023, the quarterly number of patients treated with MOUD at the NHDOC increased by more than 400% from a total of 165 patients in July-September 2021, to 685 patients in October-December 2023. At the policy level, elimination of the federal DATA-Waiver (X-Waiver) Program allowed additional providers to prescribe MOUD. At the organizational level, support from NHDOC leadership, including Medical and Forensics and the Commissioner's Office, encouraged broader engagement in MOUD from providers, multidisciplinary staff, and security. This work was augmented through receipt of State Opioid Response (SOR) dollars with a requirement to continue to advance education for NHDOC staff on the efficacy of MOUD. Resulting discussions between medical providers, experts on addiction treatment, staff and residents supported a culture change in attitudes about MOUD. During this same time window, the NHDOC made significant adjustments in the distribution of MOUD by adjusting the nursing administration process thus reducing the stigma associated with being a patient on MOUD and treating MOUD medication administration like all other medical conditions. DISCUSSION/CONCLUSIONS:Policy-related, organizational, and individual factors contributed to the expansion of the MOUD program at the NHDOC. EXIT-CJS recruitment occurred synergistically with the expansion of the MOUD program. As NHDOC was engaged as a site in EXIT-CJS, study recruitment increased awareness of extended-release treatment options among residents and staff.

OBJECTIVE:Little is known about how parenting interventions might influence families' access to related healthcare services during early childhood. This study describes the effects of a parenting intervention, Smart Beginnings (SB), on referrals to early intervention (EI) or early childhood special education (ECSE) after evaluation within a predominantly Black/Latine sample with low incomes. SB is a tiered intervention integrating a universal parenting program delivered in primary care clinics (PlayReadVIP) with a targeted home visiting program (Family Check-Up). METHODS:Data were drawn from a randomized controlled trial of SB, with sites in NYC and Pittsburgh, PA. The 280 families (132 treatment; 148 control) were 43% Black, 47% Latine, 37% Spanish-speaking, and 100% Medicaid-eligible. Hierarchical logistic regressions examined associations between expressive vocabulary and problem behaviors (internalizing and externalizing symptoms) at 2 years, and the impact of the SB intervention on the likelihood of EI/ECSE evaluation and service referrals based on evaluation results by 4 years. RESULTS:Across sites, children's lower expressive vocabulary and higher problem behaviors at 2 years predicted receiving EI/ECSE evaluation and service referrals by age 4. Assignment to the SB intervention reduced the likelihood of evaluations leading to referrals for EI/ECSE service. CONCLUSIONS:Results from this RCT showed that children with early behavior and language challenges were more likely to receive EI/ECSE evaluation and services by preschool-age. Children assigned to SB were less likely to be referred for services. Studying factors that predict EI/ECSE involvement for children from historically marginalized populations can help promote equity in early care systems.

BACKGROUND:Childhood environmental factors back to the prenatal environment can contribute to MS risk. Childhood adversity, which causes biological, behavioral, and epigenetic changes that can be passed down through families, has been understudied in MS. Here, we emphasize the need to understand the role that intergenerational adversity may play among families affected by MS. OBJECTIVE:To evaluate the frequency and types of adverse childhood experiences among parents of children with MS. METHODS:Individuals with pediatric MS (n = 68) were enrolled in a longitudinal study of cognition. At enrollment, the patient and one caregiver or parent completed questionnaires. As the pediatric participants were under age 18 at time of enrollment, one parent completed the Adverse Childhood Experiences (ACEs, a 10-item self-report measure) about the parents' own childhood. Results from the ACE questionnaire among parents of pediatric healthy controls (n = 96) and adults in a national cohort are also reported for comparison. RESULTS:Over half of pediatric MS parents reported at least one ACE exposure. Of parents that did have ACE exposures, the exposures were broad in terms of abuse, neglect, and household dysfunction. Over 10 % of parents reported total ACE scores of 7 or above. CONCLUSION/CONCLUSIONS:Over half of pediatric MS parents experienced some degree of childhood adversity. The impact of intergenerational adversity on the development of pediatric onset MS warrants further study.

INTRODUCTION/BACKGROUND:Foundational preacademic skills are crucial for academic success and serve as predictors of socioeconomic status, income and access to healthcare. However, there is a gap in our understanding of neurodevelopmental patterns underlying preacademic skills in children across low-income and middle-income countries (LMICs). It is essential to identify primary global and regional factors that drive children's neurodevelopment in LMICs. This study aims to characterise the typical development of healthy children and factors that influence child development in Bahir Dar, Ethiopia. METHODS AND ANALYSIS/METHODS:The Bahir Dar Child Development Study is a cross-sectional study implemented in two health centres, Shimbit and Abaymado and in Felege Hiwot Comprehensive Specialized Hospital (FHCSH) in Bahir Dar, Amhara, Ethiopia. Healthy children between 6 and 60 months of age will be recruited from the health centres during vaccination visits or via community outreach. Young children aged 6-36 months will complete the Global Scale for Early Development. A battery of paper and tablet-based assessments of neurocognitive outcomes including visual and verbal reasoning, executive functions and school readiness will be completed for children aged 48-60 months. Caregivers will respond to surveys covering sociodemographic information, the child's medical history and nutrition, and psychosocial experiences including parental stress and mental health. During a second visit, participants will undergo a low-field MRI scan using the ultra-low-field point-of-care Hyperfine MRI machine at FHCSH. Analyses will examine relationships between risk and protective factors, brain volumes and neurocognitive/developmental outcomes. ETHICS AND DISSEMINATION/BACKGROUND:The study is approved by the Institutional Review Boards of Addis Continental Institute of Public Health (ACIPH/lRERC/004/2023/Al/05-2024), Mass General Brigham Hospital (2022P002539) and Brown University (STUDY00000474). Findings will be disseminated via local dissemination events, international conferences and publications. TRIAL REGISTERATION NUMBER/BACKGROUND:NCT06648863.

INTRODUCTION/BACKGROUND:The number of assays on proteomic platforms has grown rapidly. The leading platforms, SomaScan and Olink, have strengths and limitations. Comparisons of precision on the latest platforms-SomaScan 11k and Olink Explore HT-have not yet been established. METHODS:Among 102 participants in the Atherosclerosis Risk in Communities Study (mean age 74 years, 53% women, 47% Black), we used split plasma samples to measure platform precision. CV and Spearman correlations were calculated for each assay. Cross-platform agreement was assessed for overlapping proteins. RESULTS:SomaScan 11k demonstrated a median correlation of 0.85 for the 10 778 assays and a median CV of 6.8%, similar precision to earlier versions. The 5420 assays on Olink Explore HT exhibited a median correlation of 0.65 and median CV of 35.7%, which was higher than observed in its predecessors (e.g., 19.8% for Olink Explore 3072). Precision of Olink assays was inversely correlated with the percentage of samples above the limit of detection (LOD) (r = -0.77). Upon replacing Olink values below the LOD with values half the LOD, the median correlation for Olink assays measured in duplicate increased to 0.79; the median CV decreased to 13.3%. The distribution of between-platform correlations for the 4443 overlapping proteins had peaks at r approximately 0 and at r approximately 0.8. One-tenth of the protein pairs had cross-platform correlations r ≥ 0.8. CONCLUSIONS:Precision of these 2 proteomics platforms in human plasma has diverged as the coverage has increased. These results highlight the need for careful consideration in platform selection based on specific research requirements.

BackgroundBreast conserving surgery represents the preferred surgical treatment option for patients with early-stage breast cancer. Reexcision rates are generally higher for patients undergoing lumpectomies for ductal carcinoma in situ (DCIS) compared to invasive breast cancer, as the microscopic extent of disease is difficult to assess during excision. This study investigated the clinicopathological characteristics of patients undergoing BCS for pure DCIS and reexcision rates over time, including the effect of the MarginProbe™ device.MethodsWe queried our prospectively maintained Institutional Breast Cancer Database for patients diagnosed with DCIS and treated with BCS as their primary procedure from 2010-2021. The primary endpoint was the rate of reexcision. Variables of interest included age at diagnosis, race/ethnicity, mode of diagnostic imaging, mammographic breast density, method of core biopsy, nuclear grade, size of DCIS, multifocality, DCIS subtype, and MarginProbe™ use.ResultsPapillary DCIS (P < 0.004) and larger size (P < 0.001) was associated with an increased reexcision rate. There were also differences in the method of core biopsy (P < 0.001), with stereotactic core biopsy predominating among patients who did not require reexcision (71.3% vs 49.5%). In an unadjusted estimate for the odds ratio for association, patients who had MarginProbe™ used were 81% less likely to require reexcision (OR = 0.19, 95% CI = 0.12, 0.31, P < 0.0001).ConclusionYounger age, papillary DCIS, larger DCIS size, and non-stereotactic core biopsy method were found to be associated with higher reexcision rates. Additionally, patients whose primary procedures included intraoperative margin assessment with the MarginProbe™ were significantly less likely to require reexcision.

IMPORTANCE/UNASSIGNED:High-quality evidence regarding suppressive valacyclovir treatment in herpes zoster ophthalmicus (HZO) is necessary to guide care. OBJECTIVE/UNASSIGNED:To determine whether suppressive valacyclovir compared with placebo delays the occurrence of new or worsening stromal keratitis (SK), endothelial keratitis (EK), iritis, or dendriform epithelial keratitis (DEK) during 12 months of treatment and if treatment benefit persisted at 18 months (secondary end point). DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:The Zoster Eye Disease Study (ZEDS) was a randomized clinical trial conducted in 95 sites from November 2017 to June 2024. Immunocompetent, nonpregnant adults with a history of an HZO rash, documented active keratitis or iritis within 1 year, and an estimated glomerular filtration rate of 45 mL/min/1.73 m2 or greater were eligible. After determined to be eligible, participants were randomized in 4 strata: age at onset (<60 years vs ≥60 years) and disease duration (<6 months vs ≥6 months). INTERVENTIONS/UNASSIGNED:A total of 12 months of double-masked daily valacyclovir, 1000 mg, or placebo. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcome was time to first occurrence within 12 months of new or worsening SK, EK, iritis, or DEK. RESULTS/UNASSIGNED:A total of 527 participants (median [IQR] age, 60 [50-68] years; 266 female [50.5%]; 266 in the valacyclovir group; 261 in the placebo group) were randomized in 4 strata; 481 completed 12 months, and 460 completed 18 months. Data were analyzed by intention to treat. At 12 months, primary end points occurred in 86 participants (33%) assigned to placebo and 74 (28%) assigned to valacyclovir, and at 18 months in 104 participants (40%) assigned to placebo and 86 (32%) assigned to valacyclovir. The hazard ratio (HR) of the primary end point at 12 months was 0.77 for participants taking valacyclovir vs placebo (HR, 0.77; adjusted 95% CI, 0.56-1.05; P = .09) and 0.73 at the secondary end point at 18 months (HR, 0.73; adjusted 95% CI, 0.55-0.97; P = .03). There was a reduction of multiple other secondary end points at 12 months (HR, 0.70; 95% CI, 0.52-0.95; P = .02) and 18 months (HR, 0.72; 95% CI, 0.55-0.95; P = .02). CONCLUSIONS AND RELEVANCE/UNASSIGNED:Although the primary outcome did not show a benefit of suppressive valacyclovir treatment, secondary study outcomes showed treatment superiority at the 18-month end point and reduced number of multiple episodes of keratitis or iritis at both 12 and 18 months. These results support consideration of 1 year of suppressive valacyclovir treatment for HZO. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT03134196.

IMPORTANCE/UNASSIGNED:Evidence regarding suppressive valacyclovir treatment on postherpetic neuralgia is necessary to guide care. OBJECTIVE/UNASSIGNED:To test the hypothesis that suppressive treatment with 1000 mg/d of oral valacyclovir for 12 months reduces the prevalence, severity, and duration of postherpetic neuralgia compared with placebo at 12 and 18 months in participants with herpes zoster ophthalmicus (HZO). DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:Multicenter, placebo-controlled randomized clinical trial including 527 immunocompetent, nonpregnant adults with history of HZO rash, documented keratitis, or iritis within 1 year and an estimated glomerular filtration rate of 45 mL/min/1.73 m2 or greater. The study was conducted at 95 participating sites (in Canada, New Zealand, and the US) from November 2017 to June 2024 and participant visits occurred every 3 months. INTERVENTION/UNASSIGNED:Treatment with 1000 mg/d of valacyclovir or placebo for 12 months. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Prevalence of postherpetic neuralgia, severity as determined by pain score (a score of ≥3 on a scale of 1-10), pain duration (≥3 months after HZO onset), and total daily dose of pain medication. RESULTS/UNASSIGNED:Of the 527 participants (490 completed 12 months of treatment and 460 completed 18 months), 73 (14%) had postherpetic neuralgia and were analyzed by age at HZO onset (<60 years or ≥60 years) and disease duration (recent [<6 months] or chronic [≥6 months]). Of the 73 participants with postherpetic neuralgia (34 in the valacyclovir group and 39 in the placebo group), the mean age was 62.4 years (SD, 13.6 years), 59% were female, 5% were Black or African American, and 10% were Hispanic. The prevalence of postherpetic neuralgia at 12 months was not reduced by valacyclovir (12/32 [38%]) compared with placebo (14/35 [40%]) (between-group difference, 2.5% [95% CI, -20.8% to 25.8%]; P>.99). The participants who were younger than 60 years at HZO onset and had a chronic disease duration had lower pain scores in the valacyclovir group (mean score, 0.3 [SD, 0.9]) vs the placebo group (mean score, 0.8 [SD, 1.9]) at 12 months (P = .045) and at 18 months (mean score, 0.2 [SD, 0.9] vs 1.0 [SD, 2.3], respectively; P = .02). There was a decrease in pain duration in the valacyclovir group at 18 months (mean, 13.6 [SD, 11.4] months) vs the placebo group (mean, 18.7 [SD, 29.5] months) (linear mixed-effects model between-group difference, -3.39 months [95% CI, -6.73 to -0.04 months]; P = .046). The total daily dose of neuropathic pain medication was lower in the valacyclovir group (mean, 271.4 [SD, 593.8] mg/d) vs the placebo group (mean, 363.4 [SD, 592.2] mg/d) at 12 months (linear mixed-effects model P = .006) and at 18 months (mean, 209.0 [SD, 412.8] mg/d vs 286.2 [SD, 577.9] mg/d, respectively; linear mixed-effects model P = .01). CONCLUSIONS AND RELEVANCE/UNASSIGNED:One year of suppressive treatment with valacyclovir was associated with a lower dosage of neuropathic pain medication. Participants in the valacyclovir group, who were younger at HZO onset and had a chronic disease duration, had lower pain scores. These secondary outcomes support consideration of 1 year of suppressive treatment with valacyclovir to reduce dosage of pain medications and pain due to HZO. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT03134196.

Parenting in very early childhood (0-2 years) provides important context for children's socioemotional development. The present study aims to address limitations of extant parenting literature, namely the reliance on white, middle-class samples and use of variable-centered approaches that often mask the rich heterogeneity of parenting styles. Using data from an efficacy trial of a tiered parenting program to promote school readiness, the current study examined parenting styles across three waves when children were 6, 18, and 24 months with a sample of Black/African American and Latina mothers with low incomes using person-oriented, latent class analysis. Based on multiple fit indices and interpretability, a three-class model was found to best fit the data. Two of the three parenting classes were identified for both Black/African American and Latina groups across all three ages: one was characterized by high levels of sensitivity, positive regard, and language quality/quantity (High Support and Warmth) and the other was characterized by moderate levels of these indicators (Moderate/Low, Moderate, and Moderate/High Support and Warmth). The third class varied the most between groups and over time. For Black/African American mothers, the third class was characterized most notably by the level of directiveness (ranging from High at 6 months, Moderate at 18 months, and Low at 24 months). For Latina mothers, this class was characterized by varying levels of directiveness and stimulation that were High at 6 months and Moderate at 18 and 24 months. Within most classes, mean levels of parenting behaviors varied by age. Findings emphasize the importance of considering age, culture, and time when assessing maternal parenting from infancy to toddlerhood.