Nevin Manimala

JAMA Netw Open. 2026 May 1;9(5):e2615005. doi: 10.1001/jamanetworkopen.2026.15005.

ABSTRACT

IMPORTANCE: Intellectual and developmental disabilities (IDDs) include cognitive and adaptive deficits beginning before ages 18 to 22 years. People with IDDs experience disparities in pregnancy and infant outcomes, yet little is known about how risks differ across IDD subtypes or the extent to which associated maternal health conditions contribute to these disparities.

OBJECTIVES: To evaluate the associations between maternal IDD subtypes and adverse infant outcomes and to estimate how much these associations may be explained by modifiable maternal health conditions.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed births in California from January 1, 2007, to December 31, 2021, using data from the Study of Outcomes in Mothers and Infants, which links vital statistics on births and infant deaths with maternal and infant hospital inpatient and emergency department records. All 6 435 742 singleton births with gestation between 22 and 44 weeks were included. Statistical analyses were completed on February 19, 2026.

EXPOSURES: Maternal IDD diagnoses, including autism spectrum disorder, cerebral palsy, intellectual disability, chromosomal differences, and other IDDs (eg, fetal alcohol syndrome, tuberous sclerosis, and congenital malformations), were identified from hospital records. Potential mediators included prenatal care utilization, prenatal tobacco use, preexisting chronic and neuropsychiatric conditions, and body mass index.

MAIN OUTCOMES AND MEASURES: Outcomes included neonatal intensive care unit (NICU) admission, small-for-gestational-age (SGA) birth, preterm birth (PTB) at less than 37 weeks, and very PTB at less than 32 weeks.

RESULTS: Of 6 435 742 singleton births, 4492 were to mothers with IDD diagnoses (mean [SD] maternal age at birth: IDD cohort, 29 [7] years; overall cohort, 30 [6] years). Infants born to mothers with IDD had higher risks of NICU admission (14% [628 of 4492] vs 5% [327 345 of 6 426 048]; adjusted risk ratio [ARR], 2.76 [95% CI, 2.56-2.98]), SGA birth (14% [614 of 4492] vs 9% [569 146 of 6 426 048]; ARR, 1.56 [95% CI, 1.44-1.68]), PTB (16% [717 of 4492] vs 7% [452 177 of 6 426 048]; ARR, 2.34 [95% CI, 2.18-2.51]), and very PTB (3% [122 of 4492] vs 1% [62 290 of 6 426 048]; ARR, 3.20 [95% CI, 2.66-3.86]) compared with infants born to mothers without IDD. Risks were highest for maternal diagnoses of chromosomal differences, other IDDs, and intellectual disability. Preexisting hypertension, epilepsy, and mental health conditions were associated with a substantial portion of the risk, particularly for NICU admission.

CONCLUSIONS AND RELEVANCE: In this cohort study of births in California, pregnant people with IDD diagnoses had substantially higher risks of adverse infant outcomes. Preexisting hypertension and neuropsychiatric conditions were key variables and may represent modifiable targets for preconception and prenatal intervention.

PMID:42201731 | DOI:10.1001/jamanetworkopen.2026.15005

JAMA Psychiatry. 2026 May 27. doi: 10.1001/jamapsychiatry.2026.1064. Online ahead of print.

ABSTRACT

IMPORTANCE: Although both recurrent copy number variants (rCNVs) and polygenic scores (PGSs) impart risk for psychiatric disorders, it remains unclear how they contribute jointly to this risk.

OBJECTIVE: To estimate and compare absolute risk of psychiatric disorders associated with rCNVs and PGSs, independently and jointly.

DESIGN, SETTING, AND PARTICIPANTS: This genetic association study applied data from the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH) case-cohort sample of individuals born in Denmark (1981-2008) and followed up until 2015, including all individuals with a hospital diagnosis of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), schizophrenia spectrum disorder (SSD), or major depressive disorder (MDD), and a subcohort randomly drawn from the source population. Data were analyzed from September 2023 to May 2025.

EXPOSURES: Carrier status was determined at 27 autosomal rCNV loci and PGSs for psychiatric (and other) outcomes from neonatal blood samples genotyped on microarrays and summary statistics from published association studies.

MAIN OUTCOMES AND MEASURES: Absolute risks were estimated for ADHD, ASD, MDD, and SSD during follow-up using a weighted survival analysis framework, and joint effects of rCNV carriage and PGSs were assessed by fitting generalized linear models.

RESULTS: In 94 276 unrelated European-ancestry individuals (mean [SD] age at follow-up, 21.9 [7.0] years; 50 653 male [53.7%]), rCNV carriage was associated with increased risk of ASD, ADHD, and SSD but not MDD (β = 0.33; 95% CI, 0.27-0.39; β = 0.29; 95% CI, 0.23-0.35; β = 0.25; 95% CI, 0.17-0.33; and β = 0.04; 95% CI, -0.03 to 0.11, respectively); each PGS was positively associated with risk of the corresponding disorder (β = 0.14; 95% CI, 0.12-0.16; β = 0.28; 95% CI, 0.26-0.30; β = 0.28; 95% CI, 0.26-0.30; and β = 0.38; 95% CI, 0.36-0.40, respectively). PGSs identified more individuals than rCNV carriage at comparable levels of absolute risk, except for ASD. A negative interaction was observed between 16p13.11 duplication and ADHD-PGS on ADHD risk (β = -0.51; 95% CI, -0.86 to -0.16), and there was a trend toward negative rCNV-PGS interaction coefficients across aggregated rCNV groups and each of the 9 most common rCNVs (27 of 39 tests, P binomial = .01).

CONCLUSIONS AND RELEVANCE: Findings of this genetic association study highlight the complementary value of rCNVs and PGSs for risk assessment in psychiatric disorders, with indications that PGSs can stratify risk among medium- and high-impact rCNV carriers and rCNV-associated risk may, in some instances, be attenuated among individuals with low PGSs.

PMID:42201728 | DOI:10.1001/jamapsychiatry.2026.1064

JAMA Psychiatry. 2026 May 27. doi: 10.1001/jamapsychiatry.2026.1078. Online ahead of print.

ABSTRACT

IMPORTANCE: Nearly all psychopathology is inherently continuous, but both clinical practice and research often require categorical decisions (eg, treat or wait, pay for treatment or decline, enroll in study or not); therefore, thresholds are applied to continuous phenomena to guide these decisions. The most common strategy is to select cutoffs by focusing on diagnoses, but this may be unhelpful in many decisions (eg, selective prevention, choice between treatment options). This review evaluates strategies for developing thresholds for psychopathology dimensions that may enhance clinical decision-making, drawing on methods used in psychiatry, psychology, internal medicine, and health economics.

OBSERVATIONS: One strategy used extensively in neuropsychology, child psychiatry, clinical psychology, and laboratory medicine is to define multiple thresholds (eg, mild, moderate, and severe), using statistical deviance vis-à-vis the general population. A second strategy is to select thresholds in reference to functional impairment, as has been done for some psychopathology measures. A third approach, common in internal medicine but underused in psychiatry, references probability of a negative outcome (eg, mortality). A fourth option, gaining momentum in European psychiatry, is to select thresholds based on costs and benefits of a clinical action at different levels of severity or risk. Common examples of these 4 strategies are reviewed, comparing their strengths and limitations. They are relevant not only to clinical measures but also research instruments. Value judgments are inherent in approaches 2, 3, and 4; thus, selection of such thresholds requires stakeholder input. Importantly, clinicians make decisions by considering all information, and thresholds are only 1 factor.

CONCLUSIONS AND RELEVANCE: Although diagnosis-focused thresholds are sometimes valuable, the field would be served best by also considering the aforementioned alternative strategies. These approaches have been greatly underused in psychiatry, and studies are urgently needed to address this gap. Herein, recommendations are offered for this research.

PMID:42201715 | DOI:10.1001/jamapsychiatry.2026.1078

JAMA Cardiol. 2026 May 27. doi: 10.1001/jamacardio.2026.1208. Online ahead of print.

ABSTRACT

IMPORTANCE: Venous thromboembolism (VTE), which encompasses deep vein thrombosis and pulmonary embolism, is a frequent condition that can lead to significant morbidity and mortality; statins, monoclonal antibody proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, and their combination are associated with a reduced risk of VTE. The effect of bempedoic acid on VTE risk is unknown.

OBJECTIVE: To determine whether bempedoic acid is associated with a reduced risk of VTE.

DESIGN, SETTING, AND PARTICIPANTS: CLEAR Outcomes was a randomized, double-blind, placebo-controlled, cardiovascular outcomes clinical trial. Statin-intolerant individuals at high risk for or with established atherosclerotic cardiovascular disease who were aged 18 to 85 years were enrolled between December 22, 2016, and August 14, 2019, in 1250 centers across 32 countries. The statistical analysis for the present study was conducted between March 10, 2025, and February 19, 2026.

INTERVENTIONS: Participants were randomized to oral bempedoic acid, 180 mg, or placebo daily.

MAIN OUTCOMES AND MEASURES: The main outcome for this analysis was the time to first occurrence of VTE (composite of deep vein thrombosis or pulmonary embolism). The occurrences of deep vein thrombosis and pulmonary embolism were also assessed.

RESULTS: A total of 13 970 participants (mean [SD] age, 65.5 [9.0] years; 6740 [48.2%] female) were randomized, 6992 to bempedoic acid and 6978 to placebo. At the time of randomization, 275 participants (2.0%) had a history of VTE, and 1219 (8.7%) were receiving systemic anticoagulation. The participants were followed up for a median (IQR) of 40.6 (37.1-46.2) months. A total of 106 VTE events occurred (39 in the bempedoic acid group and 67 in the placebo group; hazard ratio [HR], 0.58; 95% CI, 0.39-0.86; P = .006). Findings were consistent for deep vein thrombosis (HR, 0.56; 95% CI, 0.31-0.996; P = .045) and pulmonary embolism (HR, 0.61; 95% CI, 0.37-0.996; P = .046).

CONCLUSIONS AND RELEVANCE: Treatment with bempedoic acid among participants with statin intolerance at high risk for or with established cardiovascular disease was associated with a reduced risk of VTE.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02993406.

PMID:42201706 | DOI:10.1001/jamacardio.2026.1208

Infant Ment Health J. 2026 Jul;47(4):e70102. doi: 10.1002/imhj.70102.

ABSTRACT

Sex chromosome trisomies (SCTs) are genetic conditions caused by the presence of an additional sex chromosome. While recent studies have focused on analyzing the early competencies of children with SCTs, relatively few have investigated aspects of parent-child interaction. No studies have yet examined how parents support the development of children with SCTs. This study aims to (1) identify differences in supportive parenting behaviors between mothers of children with SCTs and mothers of typically developing (TD) children, and (2) observe these behaviors longitudinally at 8 months (T1) and 24 months (T2). Participants included 36 Italian mother-child dyads (19 with SCTs and 17 TD). At both T1 and T2, ten-minute semi-structured play interactions were video-recorded and coded using PICCOLO. At 8 months, mothers in the SCT group demonstrated fewer responsive and teaching behaviors than mothers in the TD group, and exhibited fewer encouraging behaviors at 24 months. However, longitudinally, the same mothers exhibited significantly more responsive and teaching behaviors at T2 than at T1. In conclusion, while awareness of their children’s condition, or differences in children’s behavior, may affect how mothers interact with their children with SCTs, these mothers also exhibit parenting skills that could benefit from targeted interventions to support their children, who are more likely to exhibit developmental delays.

PMID:42201645 | DOI:10.1002/imhj.70102

Radiol Med. 2026 May 27. doi: 10.1007/s11547-026-02224-x. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the feasibility of deriving coronary artery calcium (CAC) scores from Virtual-Non-Contrast (VNC) reconstructions obtained with dual-layer computed tomography (DLCT).

METHODS: A retrospective study was conducted on 100 patients who underwent coronary computed tomography angiography (CCTA) with a DLCT scanner. Conventional true non-contrast (TNC) images were reconstructed for CAC quantification (CAC_TNC). Post-contrast spectral datasets were processed to generate VNC reconstructions, and a 130 HU threshold was applied to calculate the volume of coronary calcified plaques (VOL_VNC). CAC values from VNC images (CAC_VNC) were derived through linear regression analysis. Correlation and agreement between CAC measurement methods were assessed using the intraclass correlation coefficient (ICC) and Bland-Altman analysis. Patients were assigned to risk categories according to Coronary Artery Calcium Data and Reporting System (CAC-DRS) to evaluate potential misclassifications.

RESULTS: The median CAC_TNC was 95 Agatston Unit (AU) [IQR:1-309], while the median CAC_VNC was 76 AU [IQR:0-340], with no statistically significant difference between the two methods (p = 0.653). An excellent correlation was found between CAC_TNC and CAC_VNC (ICC = 0.977), with good agreement demonstrated by Bland-Altman analysis, showing a mean difference of – 1.2 AU. CAC_VNC led to misclassification in 16% of patients, primarily underestimating the CAC-DRS risk category, yet maintaining strong agreement with CAC_TNC derived risk stratification.

CONCLUSIONS: VNC reconstructions from DLCT show excellent correlation and good agreement with conventional TNC images for CAC quantification. This approach has the potential to eliminate the need for a dedicated unenhanced scan, thereby reducing radiation exposure, and acquisition time while preserving diagnostic accuracy.

PMID:42201643 | DOI:10.1007/s11547-026-02224-x

Stat Med. 2026 Jun;45(13-14):e70606. doi: 10.1002/sim.70606.

ABSTRACT

Racial disparities in healthcare expenditures are well-documented, yet the underlying drivers remain complex. This study develops a framework to decompose such disparities through shifts in the distributions of mediating variables, rather than treating race itself as a manipulable exposure. We define disparities as differences in covariate-adjusted outcome distributions across racial groups, and decompose the total disparity into a component attributable to differences in mediator distributions, and a residual component that remains after equalizing those distributions. Using data from the medical expenditures panel survey (MEPS), we examine the extent to which expenditure disparities would persist or be reduced if mediators such as socioeconomic status (SES), insurance access, health behaviors, or health status were equalized across racial groups. To ensure valid inference, we derive asymptotically linear estimators based on influence-function techniques and flexible machine learning, including super learners and a two-part model designed for the zero-inflated, right-skewed nature of expenditure data. Applying this framework to MEPS data from 2009 to 2016, substantial disparities were observed across all pairwise racial comparisons, with the largest gaps observed between non-Hispanic Whites and Hispanics in both years. Differences in SES and health status were the largest contributors to these disparities, with insurance access also playing a meaningful role, particularly for Hispanic populations, whereas health behaviors contributed minimally. Residual disparities persisted, especially in comparisons involving non-Hispanic Whites, suggesting the influence of unmeasured or structural factors.

PMID:42201641 | DOI:10.1002/sim.70606

Cardiol Ther. 2026 May 27. doi: 10.1007/s40119-026-00450-y. Online ahead of print.

ABSTRACT

INTRODUCTION: Timely diagnosis and treatment are essential for improving outcomes and quality of life in patients with transthyretin (ATTR) amyloidosis. Early multisystem manifestations are often unrecognized, leading to diagnostic delays and misdiagnosis. Large-scale, multicountry, observational studies are needed to better characterize the real-world trajectory of these patients.

METHODS: OverTTuRe, an ANTHOLOGY study, is a retrospective, observational, descriptive, longitudinal, multicountry study using secondary data from claims databases, electronic health records, and healthcare registries. The primary aim of this analysis was to characterize baseline characteristics, early clinical manifestations, and outcomes in patients with hereditary transthyretin (ATTRv) amyloidosis from the United States (US), United Kingdom (UK), Japan, Denmark, and Sweden.

RESULTS: Of 1502 patients identified, the predominant phenotype across countries was ATTRv amyloidosis with polyneuropathy (ATTRv-PN 51.3-63.7%); however, many patients had ATTRv with mixed phenotype (ATTRv mixed 36.3-48.8%). Compared to patients with ATTRv mixed, patients with ATTRv-PN were younger, and a higher proportion were female (36.6-64.1% vs. 19.3-56.4%). Median (interquartile range) time from any initial cardiac or noncardiac manifestation to diagnosis varied across countries; time from any noncardiac manifestation to diagnosis was longest for both phenotypes in the US (ATTRv-PN 2.9 [1.0-4.0] years; ATTRv mixed 2.4 [0.8-3.7] years). Following diagnosis, treatment was not available for most patients. Mortality (ATTRv-PN 14.6-36.2%; ATTRv mixed 21.0-73.0%) and hospitalization (ATTRv-PN 23.5-66.2%; ATTRv mixed 20.8-70.5%) risk varied across countries in the 5 years following diagnosis. Pre- and post-diagnosis healthcare resource utilization was high for both phenotypes.

CONCLUSIONS: These findings highlight the heterogeneity of clinical manifestations and outcomes of ATTRv amyloidosis across phenotypes and countries. Patients frequently experience diagnostic delays and numerous healthcare interactions. Elevated clinical suspicion to facilitate earlier diagnosis, together with a multidisciplinary care approach and timely access to targeted therapies, is needed to improve outcomes.

TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT06355934.

PMID:42201638 | DOI:10.1007/s40119-026-00450-y

Eur Phys J E Soft Matter. 2026 May 27;49(6):43. doi: 10.1140/epje/s10189-026-00587-7.

ABSTRACT

Calanoid copepods are key components of marine and estuarine food webs. Exposure to various classes of pollutants induces changes in their swimming behavior. This raises concerns about potential effects on critical processes such as feeding, mating, predator avoidance and vertical migration. The effect of pollution by microplastics is not well known. We investigated in a large experimental tank the effects of the smallest size fraction of microplastics on the swimming behavior of the estuarine copepod Eurytemora affinis. Because the motion of zooplankton is intrinsically linked to that of the ambient fluid, we recorded copepods moving freely in calm water and in grid-generated turbulence to recreate some of the hydrodynamic conditions they experience in their natural environment. Using an advanced implementation of 3D Lagrangian particle tracking velocimetry, we simultaneously measured copepod trajectories and the surrounding flow field at high temporal resolution. In calm water, copepods alternated between periods of cruising and sudden relocation jumps. In turbulence, copepod motion was dominated by transport by the flow, yet jumps allowed copepods to deviate from the flow streamlines. The measurement of the relative velocity of copepods with respect to the underlying flow enabled us to characterize the statistics of these jumps. Turbulence significantly increased jump frequency without modifying their amplitude or duration. Following a 12-hour exposure to polyethylene fragments at 300 $\mu$ g/L, copepods showed increased jump frequency in calm water corresponding to 40 % increase in energetic cost. In contrast, exposure to microplastics produced weak additional effects on swimming behavior under turbulent conditions. These results confirm the existence of an active response to turbulence in E. affinis and are consistent with a hyperactive behavior triggered by exposure to microplastic pollution.

PMID:42201637 | DOI:10.1140/epje/s10189-026-00587-7

Intern Emerg Med. 2026 May 27. doi: 10.1007/s11739-026-04407-w. Online ahead of print.

NO ABSTRACT

PMID:42201621 | DOI:10.1007/s11739-026-04407-w