Nevin Manimala

JAMA Pediatr. 2025 May 12. doi: 10.1001/jamapediatrics.2025.0807. Online ahead of print.

ABSTRACT

IMPORTANCE: Previous studies suggest that administration of erythropoiesis-stimulating agents darbepoetin or erythropoietin to preterm infants results in fewer transfusions, fewer donor exposures, and improved neurodevelopmental outcome.

OBJECTIVE: To determine if, compared with placebo, preterm infants randomized to weekly darbepoetin would have greater red cell mass during hospitalization and better neurocognitive outcome at 22 to 26 months’ corrected age.

DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial was conducted between September 2017 and November 2019 for infants 23 0/7 to 28 6/7 weeks’ gestation in 19 US Neonatal Research Network centers comprising 33 neonatal intensive care units. Follow-up occurred through January 2023. Infants were randomized by 36 hours after birth to weekly placebo or darbepoetin (10 μg/kg) through 35 weeks’ postmenstrual age. Iron administration and transfusions were administered by protocol. Study data were analyzed from June to October 2023.

MAIN OUTCOMES AND MEASURES: The primary outcome was the mean cognitive composite score on the Bayley Scales of Infant Development, third edition (Bayley-III) at 22 to 26 months’ corrected age. The lowest possible score (54) was assigned to infants who died.

RESULTS: A total of 650 infants (322 darbepoetin; 328 placebo; mean [SD] gestational age, 26.2 [1.7] weeks; 328 female [50.5%]) were enrolled. Five hundred eighty-three infants (291 darbepoetin; 292 placebo) had the primary outcome determined (90% of those enrolled). Mean (SD) cognitive scores were similar between groups: 80.7 (19.5) darbepoetin vs 80.1 (18.7) placebo, adjusted mean difference, -0.23 (95% CI, -3.09 to 2.64). Compared with infants receiving placebo, more infants in the darbepoetin group were transfusion free (40% [127 of 319] vs 21% [70 of 327]; adjusted relative risk [RR], 1.3; 95% CI, 1.2-1.5), received fewer transfusions (mean [SD], 2.3 [3.1] vs 3.3 [3.5]), were exposed to fewer donors (mean [SD], 1.6 [2.3] vs 2.2 [2.3]), had higher red cell mass by week 2 of age (adjusted mean difference, 3.2; 95% CI, 1.7-4.7), and higher mean hematocrit by week 2 of age (adjusted mean difference, 2.8; 95% CI, 2.1-3.6), and were less likely to have bronchopulmonary dysplasia greater than grade 1 (35% [91 of 261] vs 46% [128 of 277]; RR, 0.78; 95% CI, 0.64-0.96). The incidence of retinopathy of prematurity stage greater than 2 was similar between groups, 13% (35 of 273) in the darbepoetin group vs 16% (45 of 279) in the placebo group. There were no differences in adverse effects between groups.

CONCLUSIONS AND RELEVANCE: Results of this randomized clinical trial reveal that this dose and dosing schedule of darbepoetin did not improve cognitive scores of preterm infants at 22 to 26 months’ corrected age. Darbepoetin significantly increased red cell mass resulting in higher hematocrit values, fewer transfusions, and fewer donor exposures.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03169881.

PMID:40354084 | DOI:10.1001/jamapediatrics.2025.0807

JAMA Pediatr. 2025 May 12. doi: 10.1001/jamapediatrics.2025.0828. Online ahead of print.

NO ABSTRACT

PMID:40354076 | DOI:10.1001/jamapediatrics.2025.0828

JAMA Intern Med. 2025 May 12. doi: 10.1001/jamainternmed.2025.0964. Online ahead of print.

NO ABSTRACT

PMID:40354074 | DOI:10.1001/jamainternmed.2025.0964

JAMA Pediatr. 2025 May 12. doi: 10.1001/jamapediatrics.2025.0676. Online ahead of print.

ABSTRACT

IMPORTANCE: Research documenting the pregnancy experiences of transgender boys and nonbinary youth assigned female at birth (AFAB) in the US is lacking.

OBJECTIVE: To examine AFAB youth sexual health indicators by gender.

DESIGN, SETTING, PARTICIPANTS: Self-reported data were collected cross-sectionally from 2018 through 2020. Initial analyses were conducted in 2023 and analyses were finalized in September 2024. The study took place online, across the 50 US states and Washington, DC. Eligible participants were 14 to 16 years old, read English, and had internet access.

MAIN OUTCOME: Sexual health (ie, self-reported pregnancy and sexually transmitted infections [STIs] lifetime prevalence, condom use, and use of other forms of birth control at last penile-vaginal or penile-anal sex).

RESULTS: Based on weighted data (sample sizes are unweighted), 2109 cisgender girls, 348 transgender boys, and 458 nonbinary AFAB youth were included in analyses. There were 44 transgender boys (14%; 95% CI, 9.4-20.1; P = .24), 67 AFAB nonbinary youth (14%; 95% CI, 10.8-18.8; P = .18), and 397 cisgender girls (18%; 95% CI, 16.0-19.7) who reported ever having penile-vaginal sex. Rates for penile-anal sex were also similar by gender (4% to 6%). Lifetime pregnancy rates were higher for transgender boys (5 [9%]; 95% CI, 2.7-27.1; P = .23) than cisgender (18 [4%]; 95% CI, 2.5-7.1) girls, although not statistically significantly so. Pregnancy rates were similar for AFAB nonbinary youth (5 [5%]; 95% CI, 1.9-13.3; P = .73) compared with cisgender girls. Lifetime STI rates were universally low for all AFAB youth (0.5% to 2.0%). Mean age at first penile-vaginal sex was lower for AFAB nonbinary youth (mean age, 13.6 years; SE, 0.4; P = .003) and transgender boys (mean age, 13.9 years; SE, 0.3; P = .06) compared with cisgender girls (mean age, 14.4 years; SE, 0.1). Condom use at last penile-anal or penile-vaginal sex for transgender boys (24 [16%]; 95% CI, 9.5-27.0; P < .001) and AFAB nonbinary youth (33 [24%]; 95% CI, 16.4-34.2; P < .001) was half that of cisgender girls (245 [49%]; 95% CI, 44.1-54.2). Use of birth control other than condoms at last sex was lower for AFAB nonbinary youth (18 [28%]; 95% CI, 16.2-44.5; P = .14), but similar for transgender boys (20 [42%]; 95% CI, 23.4-62.4; P = .69) compared with cisgender girls (167 [44%]; 95% CI, 38.6-50.0).

CONCLUSION AND RELEVANCE: In this cross-sectional study of sexual health among AFAB youth with a diversity of gender identities, transgender boys were more likely, and nonbinary youth, similarly likely, as cisgender girls to be pregnant during adolescence. Even though overall rates of penile-vaginal sex were similar for transgender boys and AFAB nonbinary youth compared with cisgender girls, half as many transgender boys and AFAB nonbinary youth who had this type of sex used a condom at last sex compared with cisgender girls. As with cisgender girls, transgender boys and AFAB nonbinary youth need to be engaged in affirming and inclusive sexual health education.

PMID:40354068 | DOI:10.1001/jamapediatrics.2025.0676

JAMA Intern Med. 2025 May 12. doi: 10.1001/jamainternmed.2025.1140. Online ahead of print.

ABSTRACT

IMPORTANCE: Promoting social connection among older adults is a public health priority. Addressing hearing loss may reduce social isolation and loneliness among older adults.

OBJECTIVE: To describe the effect of a best-practice hearing intervention vs health education control on social isolation and loneliness over a 3-year period in the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study.

DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis of a multicenter randomized controlled trial with 3-year follow-up was completed in 2022 and conducted at 4 field sites in the US (Forsyth County, North Carolina; Jackson, Mississippi; Minneapolis, Minnesota; Washington County, Maryland). Data were analyzed in 2024. Participants included 977 adults (aged 70-84 years who had untreated hearing loss without substantial cognitive impairment) recruited from the Atherosclerosis Risk in Communities study (238 [24.4%]) and newly recruited (de novo; 739 [75.6%]). Participants were randomized (1:1) to hearing intervention or health education control and followed up every 6 months.

INTERVENTIONS: Hearing intervention (4 sessions with certified study audiologist, hearing aids, counseling, and education) and health education control (4 sessions with a certified health educator on chronic disease, disability prevention).

MAIN OUTCOMES AND MEASURES: Social isolation (Cohen Social Network Index score) and loneliness (UCLA Loneliness Scale score) were exploratory outcomes measured at baseline and at 6 months and 1, 2, and 3 years postintervention. The intervention effect was estimated using a 2-level linear mixed-effects model under the intention-to-treat principle.

RESULTS: Among the 977 participants, the mean (SD) age was 76.3 (4.0) years; 523 (53.5%) were female, 112 (11.5%) were Black, 858 (87.8%) were White, and 521 (53.4%) had a Bachelor’s degree or higher. The mean (SD) better-ear pure-tone average was 39.4 dB (6.9). Over 3 years, mean (SD) social network size reduced from 22.6 (11.1) to 21.3 (11.0) and 22.3 (10.2) to 19.8 (10.2) people over 2 weeks in the hearing intervention and health education control arms, respectively. In fully adjusted models, hearing intervention (vs health education control) reduced social isolation (social network size [difference, 1.05; 95% CI, 0.01-2.09], diversity [difference, 0.19; 95% CI, 0.02-0.36], embeddedness [difference, 0.27; 95% CI, 0.09-0.44], and reduced loneliness [difference, -0.94; 95% CI, -1.78 to -0.11]) over 3 years. Results were substantively unchanged in sensitivity analyses that incorporated models that were stratified by recruitment source, analyzed per protocol and complier average causal effect, or that varied covariate adjustment.

CONCLUSIONS AND RELEVANCE: This secondary analysis of a randomized clinical trial indicated that older adults with hearing loss retained 1 additional person in their social network relative to a health education control over 3 years. While statistically significant, it is unknown whether observed changes in social network are clinically meaningful, and loneliness measure changes do not represent clinically meaningful changes. Hearing intervention is a low-risk strategy that may help promote social connection among older adults.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03243422.

PMID:40354063 | DOI:10.1001/jamainternmed.2025.1140

JAMA Neurol. 2025 May 12. doi: 10.1001/jamaneurol.2025.0992. Online ahead of print.

ABSTRACT

IMPORTANCE: Delandistrogene moxeparvovec is a recombinant adeno-associated virus rhesus isolate serotype 74 vector-based gene transfer therapy for the treatment of Duchenne muscular dystrophy (DMD) in patients with a confirmed pathogenic variant of the DMD gene. In a subset of patients in the EMBARK (A Gene Transfer Therapy Study to Evaluate the Safety and Efficacy of Delandistrogene Moxeparvovec [SRP-9001] in Participants With DMD) randomized clinical trial, changes in muscle health and pathology were assessed to evaluate the therapeutic impact of the treatment on disease progression.

OBJECTIVE: To determine the effect of delandistrogene moxeparvovec on muscle quantitative magnetic resonance (QMR) measures of disease progression in patients in the EMBARK trial.

DESIGN, SETTING, AND PARTICIPANTS: This was a phase 3, double-blind, placebo-controlled (October 2021-September 2023; week 52 cutoff date: September 13, 2023), multicenter randomized clinical trial that included 131 patients. Patients were randomized, and 125 were treated with either delandistrogene moxeparvovec (n = 63) or placebo (n = 62). The current study focused on a subset of patients who underwent muscle QMR imaging.

INTERVENTION: Single-administration intravenous delandistrogene moxeparvovec (1.33 × 1014 vector genome/kg) or placebo.

MAIN OUTCOMES AND MEASURES: Change from baseline to week 52 in muscle MR was a prespecified exploratory end point. Proton MR spectroscopy (MRS) and 8-point Dixon MR imaging (MRI) measured muscle fat fraction (FF); multislice spin echo MRI measured transverse relaxation time (T2). MRS FF was measured in the soleus and vastus lateralis. MRI FF and T2 were measured in 5 leg muscle locations important for ambulation. A post hoc global statistical test combining all muscles and modalities assessed overall treatment effect.

RESULTS: In this exploratory EMBARK analysis, 39 male participants (delandistrogene moxeparvovec, n = 19; placebo, n = 20; mean [SD] age, 6.10 [1.04] years; mean [SD] baseline North Star Ambulatory Assessment total score, 22.99 [3.71] points) underwent muscle MRI. Treated patients showed less disease progression vs placebo on MR measures. Across muscles and modalities, magnitudes of FF change favored delandistrogene moxeparvovec; between-group differences in least-squares mean change ranged from -1.01 (95% CI, -2.79 to 0.77; soleus) to -0.71 (95% CI, -3.21 to 1.80; vastus lateralis) for MRS FF and -3.09 (95% CI, -7.62 to 1.45; vastus lateralis) to -0.44 (95% CI, -4.01 to 3.12; hamstrings) for MRI FF. T2 reductions (improvements; 4 of 5 muscles) were observed in treated patients vs increases (worsening; all muscles) in placebo patients; within-group differences in least-squares mean change ranged from -1.06 (95% CI, -2.10 to -0.02; soleus) to 0.17 (95% CI, -1.76 to 2.10; biceps femoris) in the delandistrogene moxeparvovec group and from 1.12 (95% CI, 0.08-2.16; soleus) to 2.94 (95% CI, 0.84-5.03; quadriceps) in the placebo group. The global statistical test supported treatment benefit (P = .03).

CONCLUSIONS AND RELEVANCE: Results reveal that QMR outcomes consistently favored delandistrogene moxeparvovec across muscle groups, with treatment leading to decreased fat accumulation and improved T2 vs placebo over 52 weeks. Consistent with treatment effects on functional outcomes observed in the EMBARK trial, these results suggest stabilization or less progression of muscle pathology with delandistrogene moxeparvovec-adding to the totality of evidence supporting disease stabilization or slowing of disease progression with delandistrogene moxeparvovec.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05096221.

PMID:40354061 | DOI:10.1001/jamaneurol.2025.0992

JAMA Netw Open. 2025 May 1;8(5):e259119. doi: 10.1001/jamanetworkopen.2025.9119.

ABSTRACT

IMPORTANCE: National guidelines recommend next-generation sequencing (NGS) of tumors in patients diagnosed with metastatic prostate cancer (mPCa) to identify potential actionable alterations. Non-Hispanic Black men are poorly represented in precision oncology cohorts, and therefore differences in alterations frequencies between non-Hispanic Black and White men remain poorly characterized.

OBJECTIVES: To describe the spectrum and frequency of alterations in PCa-related genes and pathways, as well as associations with self-identified race and ethnicity and overall survival in US veterans.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study compared alteration frequencies between non-Hispanic Black and White men who underwent NGS testing from January 23, 2019, to November 2, 2023, adjusted by NGS analyte and clinicopathologic covariates. The analytic data file was locked on December 8, 2023. NGS testing was performed through the Department of Veterans Affairs (VA) National Precision Oncology Program, part of the largest near-equal access integrated health care system in the US.

EXPOSURES: Pathogenic alterations identified by NGS testing with a commercially available NGS platform.

MAIN OUTCOMES AND MEASURES: The primary outcome consisted of alteration frequencies in individual genes, actionable targets, and canonical prostate cancer pathways. Associations between alteration frequency and race and ethnicity as well as survival were also examined.

RESULTS: A total of 5015 veterans with mPCa who underwent NGS were included (1784 non-Hispanic Black [35.6%] and 3231 non-Hispanic White [64.4%]; mean [SD] age, 67.4 [9.0] years). Non-Hispanic Black veterans were younger, had higher prostate-specific antigen levels at diagnosis, were less likely to report Agent Orange exposure, and resided in more deprived neighborhoods compared with non-Hispanic White veterans. Nine of the top 10 most commonly altered genes were the same in non-Hispanic Black and non-Hispanic White veterans; however, the frequencies of alterations varied by race and ethnicity. Non-Hispanic Black race and ethnicity was associated with higher odds of genomic alterations in SPOP (odds ratio [OR], 1.7; 95% CI, 1.2-2.6) as well as immunotherapy targets (OR, 1.7; 95% CI, 1.1-2.5) including high microsatellite instability status (OR, 3.1; 95% CI, 1.1-9.4). Furthermore, non-Hispanic Black race and ethnicity was associated with lower odds of genomic alterations in the AKT/PI3K pathway (OR, 0.6; 95% CI, 0.4-0.7), androgen receptor axis (OR, 0.7; 95% CI, 0.5-0.9), and tumor suppressor genes (OR, 0.7; 95% CI, 0.5-0.8). Cox proportional hazards modeling stratified by race and ethnicity found that alterations in tumor suppressor genes, including TP53, were associated with shorter overall survival in both non-Hispanic Black (hazards ratio [HR], 1.54; 95% CI, 1.13-2.11) and non-Hispanic White (HR, 1.52; 95% CI, 1.25-1.85) veterans.

CONCLUSIONS AND RELEVANCE: This retrospective clinical genomic profiling cohort study with a large total and proportional representation of non-Hispanic Black men with mPCa reported significant differences in alteration frequencies from key oncogenic pathways but similar survival rates in the near equal-access VA health care setting. This analysis suggests the utility of genomic testing for identifying candidates irrespective of race and ethnicity for precision oncology treatments, which could contribute to equitable outcomes in patients with mPCa.

PMID:40354055 | DOI:10.1001/jamanetworkopen.2025.9119

JAMA Netw Open. 2025 May 1;8(5):e259792. doi: 10.1001/jamanetworkopen.2025.9792.

ABSTRACT

IMPORTANCE: Intrinsic capacity (IC) is a core component of the World Health Organization’s healthy aging framework. Yet, despite multiple validations of IC across various settings, there is still a lack of longitudinal cross-national analysis.

OBJECTIVE: To validate the IC construct, describe variance between key demographic groups, and create population centile curves across 15 countries using data from the Survey of Health, Aging, and Retirement in Europe (SHARE).

DESIGN, SETTING, AND PARTICIPANTS: In this population-based multicenter cohort study, data from SHARE wave 5 (January to November 30, 2013) were analyzed, and subsequent care dependence in wave 6 (January to November 30, 2015) was determined. Adults 50 years and older from SHARE wave 5 with at least 1 available measure and follow-up data in SHARE wave 6 were included. Data analyses were conducted between December 11, 2022, and June 7, 2024.

EXPOSURE: SHARE waves 5 and 6.

MAIN OUTCOMES AND MEASURES: Changes in activities of daily living (ADL) and instrumental activities of daily living (IADL). Methods included structural equation modeling, bifactor analysis, and path analysis. Construct validity was tested through multiple linear regression and validity of estimates through mediation analysis. Centile curves were established using the generalized additive models for location, scale, and shape.

RESULTS: The sample included 64 872 eligible participants aged 50 to 104 years, with a mean (SD) age of 67.24 (10.01) years, of whom 35 976 (55.46%) were women. The bifactor confirmatory factor analysis model achieved good fit (comparative fit index, 0.986; Tucker-Lewis index, 0.981), suggesting an IC structure consisting of 1 general factor and 5 subdomains. Mediation analysis indicated that IC was associated with subsequent declining performance in ADL (standard coefficient [SD], -0.213 [0.002]; P < .001) and IADL (standard coefficient [SD], -0.209 [0.002]; P < .001) after adjusting for age, gender, educational attainment, socioeconomic status, and country. Socioeconomic status was associated with IC both within and between countries. Centile curves for IC by gender and country (5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles) were constructed.

CONCLUSIONS AND RELEVANCE: Results of this cohort study of older adults suggest that IC was a valid and reliable measure that effectively captured individual-level aspects of functional ability. The centile curves developed during the study suggest that IC has the potential to serve as a benchmark for health status in older populations.

PMID:40354051 | DOI:10.1001/jamanetworkopen.2025.9792

Biomater Sci. 2025 May 12. doi: 10.1039/d5bm00033e. Online ahead of print.

ABSTRACT

Inflammation plays a key role in cartilage damage that occurs in osteoarthritis (OA). However, in vitro assessments of tissue-engineered constructs for cartilage regeneration generally do not consider their performance in the presence of inflammation. In this work, the chondrogenic differentiation potential of mesenchymal stromal cells (MSCs) was evaluated in the presence of both chondrogenic factors and inflammatory cytokines, and cartilage formation, degradative response, and inflammatory response were characterized. The addition of cytokines reduced cartilage production, increased cell proliferation, and resulted in an increase in inflammatory markers. Incorporation of hyaluronic acid (HA) had little impact on both collagen fibril microstructure and mechanical properties, two gel properties known to affect cell response, and thus allows the work to probe the biological impact of HA without the confounding effect of these gel properties. Regardless of in vitro environment, HA did not change cartilage production. The inflammatory response was similar with or without HA in terms of IL-6 and IL-10 secretion whereas IL-8 production exhibited some correlation with HA concentration as observed via a linear regression model. Additionally, in the presence of cytokines, inclusion of HA statistically decreased the gene- and protein-level expression of matrix metalloproteinase-13 (MMP-13). Thus, when exposed to both chondrogenic growth factors and inflammatory cytokines within a chondrogenic-promoting collagen I/II blended hydrogel, chondrogenic differentiation of MSCs was limited by the inflammatory environment. These findings emphasize the importance of understanding how biomaterials affect cell responses within disease-relevant inflammatory environments.

PMID:40354044 | DOI:10.1039/d5bm00033e

Eur Arch Paediatr Dent. 2025 May 12. doi: 10.1007/s40368-025-01046-1. Online ahead of print.

ABSTRACT

PURPOSE: An effective Deep learning (DL) based Early Childhood Caries (ECC) prediction model is crucial for early detection of ECC. This study aims to develop and evaluate a deep learning (DL) based hybrid statistical model for ECC prediction.

METHODS: The study employed a computational cross-sectional design, conducted over a three-year period from March 2021 to March 2024. Data analysis was carried out using a hybrid statistical approach that integrated bootstrap methods, Logistic Regression Modelling (LRM), and Multilayer Feed-Forward Neural Networks (MLFFNN). The sample comprised 157 parent-child pairs, providing a robust dataset for examining the research questions.

RESULTS: In the current study, the predictors named, “mother’s education” (β₁: 0.423; p < 0.25), “parent’s knowledge of bottle-feeding habit during sleep can cause tooth decay” (β₂: -1.264; p < 0.25), “attitude towards the importance of oral health as general health” (β₄: -1.052; p < 0.25) and “parent’s self-reported oral pain among their children” (β₅: -2.107; p < 0.25) showed significant association with ECC. For this model, the Mean Absolute Deviation (MAD) was 0.02211, Predictive Mean Squared Error (PMSE) was 0.07909, and the accuracy level was 99.98%. No significant difference was observed from the t-test between the actual values and the predicted values of the model (p > 0.05).

CONCLUSION: It has been shown that this unique deep learning-based ECC prediction model appears an effective tool with high accuracy and interpretability for ECC prediction. After implementing the oral health intervention program, focusing on the potential predictors of ECC obtained from this innovative model, policymakers could be able to evaluate their prediction models comparing their results with the findings of the current study. This comparison will guide them in understanding, designing, and implementing a more effective intervention program for ECC prevention.

PMID:40354021 | DOI:10.1007/s40368-025-01046-1