Nevin Manimala

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

Eur J Health Econ. 2026 May 27. doi: 10.1007/s10198-026-01940-5. Online ahead of print.

ABSTRACT

BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is a potentially reversible neurological condition predominantly affecting individuals over 65 years of age. Despite its treatability through cerebrospinal fluid (CSF) shunting-with clinical improvement in up to 80% of appropriately selected patients-iNPH remains substantially underdiagnosed, with only approximately 13% of affected individuals in Europe receiving appropriate care. This study evaluates the long-term epidemiological and economic burden of iNPH underdiagnosis in Italy over the decade 2024-2033, quantifying potential savings achievable through systematic diagnosis and surgical treatment.

METHODS: A dual-scenario epidemiological modeling approach was employed using Italian demographic projections from ISTAT for the population aged ≥ 65 years, stratified into two age cohorts (65-79 years and ≥ 80 years). Scenario 1 applied a conservative pooled prevalence of 1.30% derived from an international systematic review; Scenario 2 applied realistic age-stratified rates from a prospective Swedish population-based study (2.1% for ages 65-79; 8.9% for ≥ 80 years). Per-patient annual care costs (€35,866) and surgical intervention costs (€11,803) were modeled with an annual inflation adjustment of 1.78%. The Incremental Cost-Effectiveness Ratio (ICER) was calculated using a reported QALY gain of 1.7 following shunt surgery.

RESULTS: The Italian population aged ≥ 65 years is projected to grow by 16.7% over the study period, reaching 16.77 million by 2033. Estimated iNPH cases range from 186,812 (Scenario 1, conservative) to 611,435 (Scenario 2, realistic) in 2024, increasing to 217,967-707,882 by 2033. Cumulative ten-year costs to the Italian National Health System (INHS) and families without intervention ranged from €145.53 billion (Scenario 1, conservative) to €475.19 billion (Scenario 2, realistic). Systematic shunt surgery could generate cumulative savings ranging from €113.21 billion to €369.74 billion across all four modeled scenarios. The ICER was consistently -€14,166.47/QALY across all scenarios, establishing CSF shunt surgery as an economically dominant intervention.

CONCLUSIONS: iNPH underdiagnosis represents a major and escalating economic and clinical challenge for Italy’s aging healthcare system. Even under the most conservative scenario, the magnitude of avoidable costs is substantial. The consistently negative ICER confirms that CSF shunt surgery simultaneously reduces healthcare expenditure and improves patient outcomes. Urgent investment in standardized screening programs, enhanced clinical awareness among physicians, and integrated care pathways is required to address this preventable burden.

PMID:42201617 | DOI:10.1007/s10198-026-01940-5

J Robot Surg. 2026 May 27;20(1):543. doi: 10.1007/s11701-026-03511-5.

ABSTRACT

Robotic-assisted thoracic surgery (RATS) is increasingly being incorporated into contemporary practice across the United Kingdom (UK) and Republic of Ireland (ROI). However, national data on trainee exposure and preparedness is lacking. This study is the first to evaluate cardiothoracic trainees’ experiences and perceptions of training for RATS nationally. A multicentre, cross-sectional survey study was conducted between June and October 2025 of cardiothoracic trainees (ST1-ST8), post-certificate fellows, and equivalent trust appointed doctors. A 30-item, web-based questionnaire assessed institutional exposure, simulation access, operative console experience, and perceived barriers to RATS training. Quantitative data were analysed using descriptive statistics; while free-text responses underwent inductive thematic analysis. Eighty-two responses were received from all 14 training deaneries. RATS was performed in 71% (58/82) of respondents’ units; however only 16% (9/58) reported a structured training programme in place. Dual console systems were absent or unused in 43% (25/58) of robotic units. Over half (54%, 32/59) of respondents had not fully performed a single RATS procedure. Most respondents (83%, 68/82) agreed that more robotic training is required before the completion of training. Key barriers to training included lack of dual-console utilisation, operative exposure limited to bedside assisting only, and restricted simulation access. Despite widespread adoption of RATS, opportunities for structured training remain inconsistent across the UK and ROI. National standards should be developed to incorporate structured robotic training within the cardiothoracic curriculum, including access to simulation, routine dual-console use, and competency-based progression from bedside assistant to primary operator.

PMID:42201609 | DOI:10.1007/s11701-026-03511-5

Health Care Anal. 2026 May 27. doi: 10.1007/s10728-026-00573-2. Online ahead of print.

ABSTRACT

Investments in public health and education are usually examined independently, but in developing countries, both are relevant to Sustainable Economic Development (SED). Within an integrated policy framework, this study aims to examine the complementary relationship between investments in health and education and their relationship with SED. A mixed-method approach was employed, consisting of 465 questionnaire responses from participants, including government officials, and 96 semi-structured interviews. Using Partial Least Squares Structural Equation Modeling (PLS-SEM), quantitative data were analyzed, and to contextualize the statistical results, qualitative findings were involved. Results indicate that healthcare infrastructure, coupled with investment in health and education, communicable disease reduction, mental health services, and coordinated public investment, is positively and statistically related to SED. Explained variance is (R² = 0.100), showing that there is a moderate but meaningful contribution in the broader institution context. Findings contribute to existing literature by incorporating cross-sectoral modeling with qualitative institutional-level findings. It provides a more holistic understanding of the relation between coordinated human capital investments and developmental outcomes. These insights recommend integrating policies between the health and education sectors to support inclusive and sustainable development in low- and middle-income countries.

PMID:42201595 | DOI:10.1007/s10728-026-00573-2