Tag: nevin manimala

JAMA Netw Open. 2026 Apr 1;9(4):e265648. doi: 10.1001/jamanetworkopen.2026.5648.

ABSTRACT

IMPORTANCE: Risk-reducing bilateral salpingo-oophorectomy is recommended to substantially lower ovarian cancer risk in women carrying BRCA1 or BRCA2 pathogenic variant (PV). The use of hormone replacement therapy (HRT) after risk-reducing bilateral oophorectomy (RRBO), although generally recommended, remains debated due to concerns about its possible role in breast cancer (BC) risk.

OBJECTIVE: To assess the possible association between HRT use and BC incidence after RRBO in women harboring a limited range of germline BRCA PVs.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective multicenter cohort study was conducted at 3 medical centers, including both referral and primary care facilities, in Israel. Cancer-free women (aged ≥18 years) with BRCA1 PV or BRCA2 PV, with no prior mastectomy, who underwent RRBO between January 1, 2000, and December 31, 2024, and who had at least 1 year of follow-up after RRBO were included.

EXPOSURES: HRT use after RRBO.

MAIN OUTCOMES AND MEASURES: First diagnosis or incidence of invasive BC. BC diagnoses were ascertained through pathology reports and diagnostic codes used in the electronic health records; some were confirmed via participant interviews. HRT use was assessed through medical records, pharmacy dispensing data, clinic visits, and telephone interviews. Cox proportional hazards regression models, with HRT modeled as a time-varying covariate, evaluated the associations with BC risk while adjusting for potential confounders.

RESULTS: A total of 919 women (mean [SD] age at RRBO, 47.6 [8.9] years) were included, of whom 496 had BRCA1 PV and 423 had BRCA2 PV. During a mean (SD) follow-up of 8.8 (6.2) years, 144 women (16%) were diagnosed with invasive BC. Overall, 381 participants (42%) had ever used and 538 (58%) had never used HRT following RRBO. Ever use of HRT was not associated with increased BC risk (combined estrogen-progestin: hazard ratio [HR], 1.06 [95% CI, 0.67-1.68]; estrogen only: HR, 0.89 [95% CI, 0.48-1.63]). In duration of use analyses, each year of estrogen-only HRT was associated with a reduction in BC risk overall (HR, 0.90; 95% CI, 0.81-0.99) and a reduction among participants with BRCA1 PV (HR, 0.87; 95% CI, 0.77-0.98).

CONCLUSIONS AND RELEVANCE: In this cohort study of women with BRCA PV who received HRT after RRBO, estrogen-only HRT was not associated with an increased risk of BC and was associated with a lower risk of BC among women with BRCA1 PV. Combined estrogen-progestin HRT was not associated with BC risk modification.

PMID:41949865 | DOI:10.1001/jamanetworkopen.2026.5648

JAMA Netw Open. 2026 Apr 1;9(4):e265683. doi: 10.1001/jamanetworkopen.2026.5683.

ABSTRACT

IMPORTANCE: The COVID-19 pandemic and associated lockdowns resulted in changes to the way children learned, developed, and accessed health care.

OBJECTIVE: To evaluate changes in rates and rate trends of new neurodevelopmental diagnoses for children in Ontario, Canada, before, during, and after the COVID-19 pandemic.

DESIGN, SETTING, AND PARTICIPANTS: This population-based retrospective cohort study used administrative data from ICES to assess new neurodevelopmental diagnoses from March 14, 2015, to December 31, 2024, among 291 896 children aged 6 years or younger in Ontario.

EXPOSURES: The COVID-19 pandemic period, defined as March 14, 2020, to November 30, 2022, and the postpandemic period, defined as December 1, 2022, to December 31, 2024.

MAIN OUTCOMES AND MEASURES: Monthly rate of new neurodevelopmental diagnoses per 1000 child-months, defined as the total number of children with a neurodevelopmental diagnosis divided by the total number of child-months. Interrupted time series analysis using data before, during, and after the pandemic was performed to evaluate changes in rate levels or slopes between study periods.

RESULTS: A total of 291 896 children received a neurodevelopmental diagnosis during the study period. Of 1 481 844 children at risk, 130 418 received a diagnosis in the prepandemic period (mean [SD] age, 2.5 [1.6] years; 79 573 boys [61.0%]); of 1 115 791 children at risk, 86 383 received a diagnosis during the pandemic period (mean [SD] age, 2.4 [1.6] years; 52 943 boys [61.3%]); and of 1 014 792 children at risk, 75 095 received a diagnosis in the postpandemic period (mean [SD] age, 2.7 [1.6] years; 45 030 boys [60.0%]). In the prepandemic period, rates of neurodevelopmental diagnoses increased monthly (slope = 0.04; 95% CI, 0.03-0.05; P < .001). In the first month of the pandemic, rates of neurodevelopmental diagnoses decreased by 0.91 per 1000 child-months (95% CI, -1.56 to -0.25 per 1000 child-months; P = .01) compared with the expected rate in the absence of the pandemic. Rates recovered and remained stable, with no statistically significant differences in slopes between the prepandemic period and either during or after the pandemic.

CONCLUSIONS AND RELEVANCE: This population-based cohort study showed no significant differences in rates of new neurodevelopmental diagnoses among children aged 6 years or younger from prepandemic rates in the pandemic and postpandemic periods. The rapid deployment of virtual care may have helped maintain health care access, facilitating diagnoses during the pandemic and postpandemic periods.

PMID:41949864 | DOI:10.1001/jamanetworkopen.2026.5683

JAMA Netw Open. 2026 Apr 1;9(4):e265695. doi: 10.1001/jamanetworkopen.2026.5695.

ABSTRACT

IMPORTANCE: A long-acting monoclonal antibody (nirsevimab) for use in infants aged 7 months or younger and an antenatal respiratory syncytial virus (RSV) vaccine (RSVpreF) became available in Washington state in 2023.

OBJECTIVE: To estimate the combined population-level impact of nirsevimab and antenatal RSV vaccine on the relative rate of RSV-associated hospitalizations and emergency department (ED) visits among infants during the first 2 respiratory seasons of use.

DESIGN, SETTING, AND PARTICIPANTS: This difference-in-diferrences cohort study used data from the Washington state syndromic surveillance program on RSV-associated hospitalizations and ED visits among infants from July 1, 2022, to June 30, 2025.

EXPOSURE: Introduction of nirsevimab for infants and antenatal RSVpreF.

MAIN OUTCOMES AND MEASURES: A difference-in-differences analysis was conducted to estimate mean relative changes in the rate of RSV-associated hospitalizations and ED visits between the period before and the period after introduction of RSV prevention products for children aged 7 months or younger (treatment group) beyond that for children aged 8 to 24 months (comparison group) using negative binomial models. Relative changes were estimated separately for July 1, 2023, to June 30, 2024, and July 1, 2024, to June 30, 2025, vs July 1, 2022, to June 30, 2023.

RESULTS: During July 2022 to June 2025, there were 16 775 RSV-associated hospitalizations and ED visits among children aged 24 months or younger in Washington state (median age, 10 months [IQR, 4-19 months]; 9228 male [55%]). The median age increased from 9 months (IQR, 3-19 months) during 2022-2023 to 12 months (IQR, 6-21 months) during 2024-2025. During the first year of limited use of RSV prevention products (2023-2024), estimates did not indicate a significant decrease in the rate of RSV-associated hospitalizations and ED visits among children aged 7 months or younger beyond temporal trends also observed for children aged 8 to 24 months (ratio of relative rates, 0.92 [95% CI, 0.80-1.03]). In the second year of use (2024-2025), there was an estimated 43.0% (95% CI, 32.0%-52.1%) relative decrease in the rate of RSV-associated hospitalizations and ED visits among children aged 7 months or younger beyond that for children aged 8 to 24 months. Relative changes were similar across racial groups, except for Native Hawaiian or Other Pacific Islander children. The estimated impact in 2024-2025 was 1.77 times (95% CI, 1.17-2.66 times) higher for White vs Native Hawaiian or Other Pacific Islander children.

CONCLUSIONS AND RELEVANCE: In this cohort study of children aged 24 months or younger, nirsevimab and antenatal RSVpreF vaccine were associated with a reduced burden of RSV-associated hospitalization and ED visits among infants aged 7 months or younger. Results support continued use of these products in the state. Increased coverage will likely be associated with additional decreases in severe disease burden, particularly among populations at increased risk.

PMID:41949863 | DOI:10.1001/jamanetworkopen.2026.5695

JAMA Psychiatry. 2026 Apr 8. doi: 10.1001/jamapsychiatry.2026.0181. Online ahead of print.

ABSTRACT

IMPORTANCE: Early diagnosis of attention-deficit/hyperactivity disorder (ADHD) is often recommended, but it is unknown whether age at diagnosis is associated with educational outcomes.

OBJECTIVE: To estimate whether age at ADHD diagnosis is associated with school performance, completed degrees, educational enrollment, and school dropout.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study used national registry data for individuals born in Finland between January 1, 1990, and December 31, 1999, followed up until age 20 years. Individuals were born without a diagnosis of intellectual disability (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] codes F70-F79). Analyses were conducted from May 2024 to December 2025.

EXPOSURES: Age at ADHD diagnosis, identified by the first clinical diagnosis (International Classification of Diseases, Ninth Revision code 314; ICD-10 code F90; or medication purchase).

MAIN OUTCOMES AND MEASURES: Grade point average (GPA; range, 4 [failing] to 10 [excellent]) at the end of compulsory education (approximately 16 years of age), completed degrees in upper secondary education (vocational or academic), enrollment in tertiary education, and school dropout at age 20 years.

RESULTS: The study sample included 580 132 individuals (51.2% male). Of these, 12 208 males (2.1%) and 3753 females (0.7%) had a first ADHD diagnosis between ages 4 and 20 years: mean (SD) age for males was 11.3 (4.1) years and for females was 14.4 (4.6) years. ADHD diagnosis at any age was associated with worse educational outcomes and greater likelihood of vocational than academic upper secondary education. After adjusting for sociodemographic covariates, if a diagnosis was received by age 16 years, younger age was associated with higher GPA for males (range, 7.12 [95% CI, 6.99-7.26] at age 4 years to 6.52 [95% CI, 6.46-6.58] at age 16 years) and females (range, 7.64 [95% CI, 7.49-7.78] at age 6 years to 6.95 [95% CI, 6.82-7.07]) at age 12 years, higher probability of completing an academic upper secondary degree for males (range, 20.77% [95% CI, 15.41%-26.12%] at age 4 years to 5.29% [3.78%-6.80%] at age 15 years) and females (range, 31.04% [95% CI, 15.60%-46.47%] at age 4 years to 12.01% [95% CI, 7.80%-16.21%] at age 14 years), and lower probability of school dropout for males (range, 9.16% [95% CI, 4.89%-13.42%] at age 4 years to 29.52% [95% CI, 25.85%-33.19%] at age 16 years) and females (range, 9.57% [95% CI, 4.49%-14.65%] at age 6 years to 27.16% [95% CI, 19.75%-34.57%] at age 13 years). However, after educational track choices (ages 17-20 years), older age at diagnosis was associated with higher and more academic education.

CONCLUSIONS AND RELEVANCE: In this cohort study, earlier age at ADHD diagnosis was associated with better school performance, more academic education, and lower school dropout rates than diagnoses closer to age 16 years. The findings suggest that individuals who are diagnosed closer to age 16 years could benefit from targeted support to prevent school dropout.

PMID:41949840 | DOI:10.1001/jamapsychiatry.2026.0181

J Occup Environ Med. 2026 Apr 8. doi: 10.1097/JOM.0000000000003733. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the role of PM2.5 speciation chemical mixtures in association with cardiovascular disease (CVD) risk factors during pregnancy.

METHODS: PM2.5 chemical mixtures are identified using novel statistical method. Logistic regression analyses were conducted to assess mixtures associated with CVD risk factors after controlling for known risk factors.

RESULTS: Direct Association between a PM2.5 chemical mixture and hyaline disease as well as association between some mixtures and preeclampsia, hyaline disease and gestational diabetes through interaction with race and ethnicity have been identified. The results also emphasized the need for new statistical methods for environmental health study especially when dealing with spatial-temporal data.

CONCLUSION: The study highlights the importance of considering chemical mixtures in exposure assessment and the need for more refined methodologies in future environmental health investigations.

PMID:41949838 | DOI:10.1097/JOM.0000000000003733

JAMA Psychiatry. 2026 Apr 8. doi: 10.1001/jamapsychiatry.2026.0190. Online ahead of print.

ABSTRACT

IMPORTANCE: Ketamine has well-known dissociative, analgesic, and antidepressant properties, but it is unknown whether the neurophysiologic effects that are associated with these properties can be modulated separately from one another. Considering that specific cortical oscillations have been associated with specific therapeutic effects, modulating selective aspects of ketamine neurophysiology could inform efforts to develop more targeted therapies.

OBJECTIVE: To determine whether the neurophysiologic signatures of ketamine are associated with removal of conscious awareness using general anesthesia (GA).

DESIGN, SETTING, AND PARTICIPANTS: This cohort study was a secondary analysis of participant-level data from 3 prospective studies conducted between 2017 and 2023. The primary analysis included data from 2 study cohorts (University of Michigan and Stanford University), and the supplementary analysis included data from a third cohort (University of Auckland). The study cohorts included healthy volunteers, patients undergoing elective surgery, and patients with a diagnosis of depression (all aged ≥18 years).

EXPOSURE: Participants received a subanesthetic infusion of ketamine (0.5 mg/kg body weight) over 40 minutes or placebo with or without GA.

MAIN OUTCOMES AND MEASURES: The primary outcome was change in electroencephalographic (EEG) band power during medication infusion. Changes were computed using nonparametric paired statistical text (Wilcoxon signed-rank test).

RESULTS: This study included 52 participants in the primary analysis (mean [SD] age, 43.4 [18.3] years; 34 females [65.4%]) and 27 additional participants in the supplementary analysis (mean [SD] age, 30.2 [8.2] years; 15 females [55.6%]). GA differentially altered EEG features commonly associated with ketamine in all 52 participants (100%) in the primary analysis. Compared with awake administration, ketamine administered during GA preserved its βγ power modulation (mean [SEM] increase from 6.3 [11.3] to 11.6 [2.2] dB for awake administration; increase from 8.5 [2.9] to 11.2 [3.8] dB for administration during GA) but lacked its characteristic θ augmentation (increase from 17.3 [10.5] to 22.9 [3.1] dB during awake administration; nonsignificant decrease from 29.0 [3.0] to 27.8 [3.5] dB for administration during GA).

CONCLUSIONS AND RELEVANCE: In this cohort study, coadministration of ketamine with GA selectively modulated the θ but not the βγ neurophysiologic correlates of ketamine. These findings suggest a potential method to explore the role of these components in the behavioral effects of ketamine.

PMID:41949829 | DOI:10.1001/jamapsychiatry.2026.0190

MAGMA. 2026 Apr 8. doi: 10.1007/s10334-026-01351-w. Online ahead of print.

ABSTRACT

OBJECTIVES: Magnetic resonance spectroscopic imaging (MRSI) is a non-invasive technique for probing metabolism. MRSI enables spatial mapping of metabolite distributions, offering insights into regional metabolic heterogeneity that single-voxel spectroscopy (SVS) cannot capture. However, MRSI produces large multidimensional datasets and requires complex processing pipelines, limiting reproducibility and accessibility. While human studies benefit from advanced processing tools, similar developments in preclinical research remain scarce, highlighting a demand for practical tools accessible to non-experts. Furthermore, recent advances in deuterium-based MRSI have opened metabolic pathway studies, introducing additional dimensions for kinetic information and specific positional labeling, thus substantially increasing dataset complexity and analysis demands.

METHODS: To address these needs, we introduce the MRS4Brain Toolbox, a freely available MATLAB-based platform for preclinical MRSI supporting proton, deuterium, and other nuclei, with extended functionalities for SVS and diffusion-weighted spectroscopy.

RESULTS: The toolbox integrates reconstruction, preprocessing, quantification, quality control, brain segmentation automatically overlaid on metabolite maps, modeling, and statistical analysis into unified workflows accessible via a graphical interface.

CONCLUSION: By streamlining data processing and reducing technical barriers, MRS4Brain Toolbox promotes reproducibility, harmonization, and broader adoption of basic and advanced spectroscopic techniques in preclinical studies, ultimately facilitating translational metabolic research.

PMID:41949812 | DOI:10.1007/s10334-026-01351-w

Shock. 2026 Mar 20. doi: 10.1097/SHK.0000000000002725. Online ahead of print.

ABSTRACT

INTRODUCTION: Calibrated automated thrombography (CAT) assay parameters have been shown to assess hypercoagulation state and, therefore, may independently predict post-trauma, symptomatic venous thromboembolism (VTE). Yet, CAT lacks high throughput and standardization, limiting diagnostic potential. This study analyzed thrombin generation profiles in trauma patients using a high throughput assay, processing up to 10 samples at once, providing batch testing capabilities. We hypothesized that trauma patients who developed VTE would show distinct thrombin generation profiles compared to those who did not.

METHODS: Trauma patients presenting to a Level I Trauma Center had samples collected within 12 hours post-injury prospectively. Follow-up was conducted to 90 days, time to symptomatic VTE diagnosis or death, confirmed via autopsy or imaging. Thrombin generation profiles were measured from the ST Genesia assay. Data was presented as median [IQR] or n (%), with Wilcoxon rank-sum or chi-squared test. Associations between thrombin generation parameters and clinical risk factors were assessed using Spearman correlation analysis or the Wilcoxon rank-sum test.

RESULTS: Two-hundred and fifty-four trauma patients were analyzed (48.5 years [31.0, 62.0], 72.0% male): 64 patients with VTE (25.2%) to 190 with non-VTE. VTE pts had a median time to VTE of 8 days, with 29 developing deep venous thrombosis (DVT), 24 with pulmonary embolism (PE), and 11 with DVT/PEs. No significant differences were found in age, sex, or Body Mass Index (BMI); significantly more VTE patients underwent surgery and blood transfusions within 24 hours. Thrombin generation profiles demonstrated accelerated thrombin generation in patients who developed VTE compared to non-VTE, with significant differences in Peak Height (p=0.001), Time to Peak (p=0.021), Endogenous Thrombin Potential (p<0.001) and Velocity Index (p=0.001).

CONCLUSION: Thrombin generation profiles using ST Genesia can differentiate trauma patients at high risk of developing VTE. The platform suits clinical labs needing high throughput by providing batch testing capabilities.Study Type: Prospective study with less than large effect and no negative criteria.Level of Evidence: II.

PMID:41949808 | DOI:10.1097/SHK.0000000000002725

Ophthalmic Physiol Opt. 2026 Apr 8. doi: 10.1007/s44402-026-00076-6. Online ahead of print.

ABSTRACT

PURPOSE: To refit contact lens (CL) dropouts who dropped out of CLs because of dryness or discomfort into lehfilcon A (TOTAL30®) monthly, spherical CLs to determine the frequency that they can be comfortably refitted into CLs.

METHODS: A 6-month, four-visit, multi-centre, open-label, single-arm, six-site study was conducted in the United States. Adults, 18- to 40-year-old, past CL wearers who dropped out of reusable CLs at least 3 months but not more than 2 years ago because of discomfort or dryness were enrolled. Participants were required to have no significant dry eye symptoms (SPEED scores ≤3). All participants were then fitted into lehfilcon A CLs. The participants were evaluated with the SPEED, a comfort visual analogue scale (VAS; 0-100 scale) and a Likert questionnaire.

RESULTS: This study enrolled 61 participants who had a median (interquartile) age of 28 (7) years (78.7% female). The participants had a right eye median (IQR) refractive error (sphere/cylinder power) of -1.50 D (2.50 D)/-0.50 D (0.50 D). This study had a CL retention rate of 98.4% at 1 month and 65.6% at 6 months. The VAS yielded a median comfort score of 81 (40) at 6 months. The Likert questionnaire found that 80.7% of participants would recommend the CLs to a friend at 6 months. SPEED scores increased statistically after resuming CL wear (p = 0.0001) at 1 month, yet this symptom change was unlikely to be clinically meaningful.

CONCLUSIONS: This study found that previous CL wearers who had dropped out of CLs could be comfortably refitted with lehfilcon A monthly replacement, silicone hydrogel CLs, with most of them continuing to wear the CLs after 6 months of daily wear. The results suggest that the monthly soft CLs with water gradient technology can be a viable option for many CL dropout sufferers.

PMID:41949795 | DOI:10.1007/s44402-026-00076-6

Ophthalmic Physiol Opt. 2026 Apr 8. doi: 10.1007/s44402-026-00058-8. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the effect of nightly 0.01% atropine eye drops on choroidal thickness (ChT) in pre-myopic children (at risk of myopia).

METHODS: In a 12-month randomised, double-blind, placebo-controlled trial, 54 children aged 5-12 received nightly 0.01% atropine or placebo in both eyes. ChT was measured in 15 macular sectors using swept-source OCT at baseline and every 3 months. Longitudinal mixed-effects models (LMM) compared ChT changes between groups, and an unsupervised clustering analysis of individual ChT trajectories was performed.

RESULTS: Both groups showed progressive choroidal thinning. At 12 months, atropine-treated eyes showed a trend towards less choroidal thinning than placebo, especially in the central, inferior and temporal macular areas, but between-group differences did not reach statistical significance after multiple comparison correction. Clustering of ChT trajectories revealed two exploratory clusters: a “Thinning-dominant” pattern with pronounced mid-year thinning (6-9 months) followed by partial recovery by month 12 and a “Stable ChT” pattern with minimal change. Eyes in the Thinning-dominant group had faster axial elongation than the Stable group, suggesting an association between ΔChT clusters and ocular growth.

CONCLUSIONS: Nightly low-dose atropine in pre-myopic children showed a non-significant trend toward reduced macular choroidal thinning. Clustering and early-change analyses revealed heterogeneity in ChT responses and exploratory associations with ocular growth. These findings require external validation and do not support early ΔChT as a clinically actionable treatment-response marker.

PMID:41949791 | DOI:10.1007/s44402-026-00058-8