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Nevin Manimala Statistics

Mapping Fatty Acid Composition in the Human Knee: Short-Term Repeatability at 3T

J Magn Reson Imaging. 2026 Jun 25. doi: 10.1002/jmri.70396. Online ahead of print.

ABSTRACT

BACKGROUND: Alterations in periarticular lipid composition are implicated in musculoskeletal diseases, yet short-term reliability of MRI-based triglyceride composition mapping in the knee is not fully established.

PURPOSE: To evaluate 1-week repeatability of proton-density fat fraction (PDFF) and triglyceride fatty-acid composition-saturated (SFA), monounsaturated (MUFA), and polyunsaturated (PUFA)-in periarticular knee tissues.

STUDY TYPE: Prospective.

POPULATION: Ten healthy adults (5 female, 5 male; age 32 ± 8 years; BMI 23.5 ± 2.4 kg/m2).

FIELD STRENGTH/SEQUENCE: 3T; 12-echo 3D spoiled gradient-echo acquisition for chemical shift-encoded fat quantification and a proton density-weighted SPACE sequence for segmentation (0.6 mm isotropic).

ASSESSMENT: Participants underwent repeated MRI 1 week apart. Femoral and tibial bone marrow, patella, Hoffa’s fat pad, prefemoral fat pad, quadriceps fat pad, posterior fat pad, and subcutaneous adipose tissue were segmented and rigidly aligned. Voxelwise spectral fitting was used to estimate PDFF and fatty acid composition, including SFA, MUFA, and PUFA components. Repeatability metrics included bias, within-subject standard deviation (wSD), within-subject coefficient of variation (wCV%), coefficient of repeatability, and intraclass correlation coefficient (ICC).

STATISTICAL TESTS: Paired t-tests assessed systematic differences (α = 0.05); ICCs used a two-way random-effects, absolute-agreement model (ICC(2,1)).

RESULTS: PDFF showed lowest variability across all regions (wCV: 1.5%-5.9%; ICC: 0.33-0.96). SFA demonstrated similar stability (wCV: 2.4%-12.6%; ICC: 0.19-0.87). MUFA exhibited anatomy-dependent reliability (wCV: 4.1%-21.1%; ICC: 0.17-0.97), with highest repeatability in subcutaneous adipose tissue (ICC: 0.97) and Hoffa’s fat pad (ICC: 0.85). PUFA displayed the greatest variability (wCV: 3.6%-52.8%; ICC: 0.10-0.94), with the greatest instability in periarticular fat pads. No paired comparisons were significant (all p > 0.05; range p = 0.14-0.98). Regional ordering remained consistent across sessions.

DATA CONCLUSION: A 12-echo chemical shift-encoded MRI protocol provides repeatable PDFF and SFA measurements over 1 week. MUFA reliability varies by tissue, while PUFA remains least stable.

EVIDENCE LEVEL: 2 (Prospective cohort).

TECHNICAL EFFICACY STAGE: 2 (Reproducibility/feasibility evaluation).

PMID:42348313 | DOI:10.1002/jmri.70396

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ESTELA-Study: Long-Term Effectiveness and Safety of Anti-Calcitonin Gene-Related Peptide Monoclonal Antibodies in Real-World Clinical Practice

Brain Behav. 2026 Jun;16(6):e71560. doi: 10.1002/brb3.71560.

ABSTRACT

BACKGROUND: Anti-CGRP antibodies are effective and safe in real-world migraine management, but guidelines recommend discontinuation after 12-18 months due to limited long-term data and remaining uncertainties regarding optimal treatment duration and sustained safety, highlighting the need for large-scale long-term real-world evidence. This study evaluated their safety and effectiveness in patients treated for ≥2 years.

METHODS: This multicenter retrospective study included patients from 13 headache units who received the same anti-CGRP antibody for ≥24 months, excluding discontinuation periods. Baseline characteristics, monthly headache days (MHD), monthly migraine days (MMD), and adverse events (AEs) were recorded at baseline, 6 months, 1, 2, 3, and 4 years. Descriptive statistics were used to summarize clinical characteristics, and appropriate parametric or non-parametric tests were applied for group comparisons. Multivariate analyses were performed to explore associations between baseline variables and long-term treatment response.

RESULTS: A total of 454 patients (91% female, mean age 48) were analyzed, with follow-up at 2 years (n = 454), 3 years (n = 135), and 4 years (n = 17). Treatments included erenumab (39%), galcanezumab (34%), and fremanezumab (27%). Fifty-seven percent maintained continuous therapy, while 43% restarted after discontinuation. Sustained reductions in MHD and MMD were observed at 2, 3, and 4 years (MHD from 20 to 6, 6, 5/MMD from 14 to 4, 4, and 2). Medication overuse decreased from 78% to 13%, 20%, and 18%. Loss of effectiveness occurred in 4.2% after 2 years. AEs appeared in <20%, mostly mild (>80%), leading to discontinuation in 0.4%. Multivariate analysis showed that shorter disease duration prior to anti-CGRP initiation, earlier anti-CGRP initiation, and greater MHD/MMD reduction at 6 months were associated with better long-term outcomes.

CONCLUSIONS: Anti-CGRP mAbs demonstrate sustained long-term safety and effectiveness, with consistent reduction in headache and migraine days and lower medication overuse. Early initiation and greater initial improvement predict better long-term outcomes. Findings support extending therapy beyond 12-18 months, supporting optimization of clinical protocols.

PMID:42348309 | DOI:10.1002/brb3.71560

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Nevin Manimala Statistics

Causal Effects on Nonterminal Event Time With Application to Antibiotic Usage and Future Resistance

Stat Med. 2026 Jul;45(15-17):e70650. doi: 10.1002/sim.70650.

ABSTRACT

Comparing future antibiotic resistance levels resulting from different antibiotic treatments is challenging because some patients may survive only under one of the antibiotic treatments. We embed this problem within a semi-competing risks approach to study the causal effect on resistant infection, treated as a nonterminal event time. We argue that existing principal stratification estimands for such problems exclude patients for whom a causal effect is well-defined and is of clinical interest. Therefore, we present a new principal stratum, the infected-or-survivors ( i o s $$ ios $$ ). The i o s $$ ios $$ is the subpopulation of patients who would have survived or been infected under both antibiotic treatments. This subpopulation is more inclusive than previously defined subpopulations. We target the causal effect among these patients, which we term the feasible-infection causal effect (FICE). We develop large-sample bounds under novel assumptions, and discuss the plausibility of these assumptions in our application. As an alternative, we derive FICE identification using two illness-death models with a bivariate frailty random variable. These two models are connected by a cross-world correlation parameter. Estimation is performed by an expectation-maximization algorithm followed by a Monte Carlo procedure. We apply our methods to detailed clinical data obtained from a hospital setting.

PMID:42348288 | DOI:10.1002/sim.70650

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Can the All of Us sample be reweighted to mirror a nationally representative sample? A comparison of mortality predictors

Epidemiology. 2026 Jun 25. doi: 10.1097/EDE.0000000000002016. Online ahead of print.

ABSTRACT

BACKGROUND: Participants in the All of Us research study differ from the U.S. population in myriad characteristics, limiting the generalizability of findings. A statistical reweighting tool to improve generalizability would enhance the scientific value of the data.

METHODS: To account for differences between All of Us and the nationally representative 1999-2018 National Health and Nutrition Examination Survey (NHANES), we generated selection weights using four models incorporating sociodemographic, self-reported health, and clinical characteristics. We assessed covariate balance and compared predictors of all-cause mortality in weighted All of Us to NHANES using the ratio of hazard ratios (RHRs), where an RHR of one indicates unbiased estimates in (weighted) All of Us relative to NHANES.

RESULTS: Weighting improved balance on measured variables between All of Us and NHANES. Among the four weighting models, the most complex model which included sociodemographic, health, and clinical variables and their interactions achieved HRs in All of Us most similar to those in NHANES. For example, the RHR for hypertension for unweighted All of Us vs. NHANES (RHR=1.5; 95% CI=1.4 to 1.7) was reduced to 1.2 (95% CI=0.9 to 1.5) after applying weights from the clinical-interaction model. Even in this model, 17 of 35 HRs evaluated diverged by >20% (RHR <0.8 or >1.2) between weighted All of Us and NHANES.

CONCLUSIONS: Predictors of mortality in All of Us differ from those in the U.S. population both in their distribution and in their associations with mortality. Reweighting can mitigate selection bias, but no model we tested comprehensively achieved generalizability.

PMID:42348262 | DOI:10.1097/EDE.0000000000002016

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Reducing Anaesthesia’s Carbon Footprint: A Survey of Awareness and Attitudes

Ir Med J. 2026 Jun 18;119(6):110.

ABSTRACT

AIMS: This study aimed to explore Irish anaesthesiologists’ attitudes toward environmentally sustainable anaesthesia, including perceptions of safety, efficacy, and policy influences on anaesthetic choice.

METHODS: A cross-sectional online survey was distributed to anaesthesiologists across Ireland between March and June 2025. The questionnaire assessed demographic factors, preferences for intravenous versus inhalational anaesthesia, environmental awareness, and institutional support. Descriptive and comparative statistical analyses were performed.

RESULTS: A total of 98 responses were received. Patient factors and ease of administration were the primary determinants of anaesthetic choice, while cost was less influential. Environmental considerations were common, with 71 (72%) reporting they consider environmental impact when selecting an anaesthetic technique. Most respondents (n=86, 88%) were willing to modify their practice to reduce environmental harm, yet 55 (56%) felt their institution did not provide adequate environmental education or guidance.

DISCUSSION: Irish anaesthesiologists demonstrate strong awareness and willingness to engage in sustainable practice, but institutional training and policy support remain limited. Targeted education and system-level initiatives may enhance environmentally responsible anaesthetic care.

PMID:42348256

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Growing together: Developmental integration and modularity in the human talus-calcaneus complex

J Anat. 2026 Jun 25. doi: 10.1111/joa.70186. Online ahead of print.

ABSTRACT

This study investigates age-related shape changes, morphological integration, and modularity in the human talus-calcaneus complex throughout postnatal development (0-10 years). Geometric morphometric analyses were performed on three-dimensional landmark data from 23 individuals binned into four age groups, considering both the talus and calcaneus. Statistical analyses included Procrustes ANOVA to assess age effects, two-block partial least squares to quantify inter-bone integration, and Covariance Ratio tests to evaluate modular organization within each bone. Trabecular bone architectural parameters from micro-CT scans were analyzed in parallel. Marked age-related shape changes were detected in both the talus and calcaneus, with pronounced morphological transitions observed between the middle age groups (1-3 and 3-6 years). The two bones exhibited strong morphological integration across all age classes, representing the first quantitative assessment of talus-calcaneus integration during ontogeny. Modular organization was confirmed also within each bone. Trabecular bone architectural analysis via micro-CT revealed distinct developmental patterns: the talus exhibited higher initial bone volume fraction with subsequent stabilization and stable trabecular thickness, while the calcaneus showed progressive increases in both bone volume fraction and trabecular thickness, alongside higher anisotropy values, presumably reflecting adaptation to its more direct role in experiencing impact forces during heel strike. The talus-calcaneus complex exhibits highly coordinated ontogenetic timing and strong morphological integration across both external morphology and internal trabecular architecture. These adaptations highlight the sophisticated interplay within this skeletal unit, supporting its function as an integrated biomechanical system critical for understanding human locomotor evolution and foot development.

PMID:42348250 | DOI:10.1111/joa.70186

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Dynamic Quality-of-Life Trajectories After Head and Neck Reconstruction

JAMA Otolaryngol Head Neck Surg. 2026 Jun 25. doi: 10.1001/jamaoto.2026.1584. Online ahead of print.

ABSTRACT

IMPORTANCE: Quality of life (QOL) is considered the second most important outcome after survival in cancer care. In head and neck reconstruction, QOL has long been assumed to stabilize at 1 year, an assumption that guides clinical follow-up and trial design.

OBJECTIVE: To evaluate QOL beyond 1 year after head and neck reconstruction.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study of 315 patients with head and neck disease was conducted from 2015 through 2023 at a high-volume tertiary center in Taiwan. Data were analyzed March to August 2025.

EXPOSURE: Free flap reconstruction.

MAIN OUTCOMES AND MEASURES: The primary outcome was the physical domain of the University of Wisconsin QOL questionnaire. The primary end point was QOL time to deterioration (TTD), which accounts for reversibility and patient response shift, and to identify modifiable risk factors for deterioration, defined in TTD as a decline of 5 or more points without subsequent recovery of 5 or more points. For Cox proportional hazards models, statistical analysis included hazard ratios (HRs) with 95% CIs. The secondary end point was a composite of TTD or death.

RESULTS: Among 315 patients (mean [SD] age, 53.7 [11.8] years; 283 [89.8%] male; median follow-up, 1155 [95% CI, 1056 to 1254] days), baseline Cox models identified Charlson Comorbidity Index as associated with QOL deterioration (HR, 1.46; 95% CI, 1.22 to 1.74). In 12-month landmark models (N = 272), Charlson Comorbidity Index (HR, 1.70; 95% CI, 1.43 to 2.06), chemotherapy (HR, 1.60; 95% CI, 1.03 to 2.48), and complications (HR 2.01; 1.21 to 3.34) were associated with QOL deterioration. The composite end point showed similar results. QOL remained dynamic beyond 1 year, with 115 of 192 patients (59.9%) having clinically meaningful score changes between years 1 and 2 (58 of 192 [30.2%] improved, 57 of 192 [29.7%] deteriorated) despite stable cohort mean scores. Findings were consistent in analyses restricted to patients with malignant disease (n = 246). Exploratory baseline and 12-month risk scores demonstrated the feasibility of predicting dynamic QOL changes beyond 1 year.

CONCLUSIONS AND RELEVANCE: Results of this cohort study question the assumption that QOL stabilizes at 1 year after head and neck reconstruction. More than half of patients continued to experience clinically meaningful changes, with complications at 1 year representing the strongest modifiable risk factor for deterioration. Prognostic QOL risk scores provide an approach for targeting survivorship interventions to patients at highest risk for deterioration, shifting the focus from survival alone to preservation of QOL.

PMID:42348233 | DOI:10.1001/jamaoto.2026.1584

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From Core to Front: Microplastic Loads Along a Signal Crayfish (Pacifastacus leniusculus) Invasion Gradient

Environ Toxicol Chem. 2026 Jun 25:vgag174. doi: 10.1093/etojnl/vgag174. Online ahead of print.

ABSTRACT

Plastic pollution is one of the most persistent threats to aquatic ecosystems, yet studies in low-disturbed mountain aquatic environments remain scarce. This study examined the presence of macro- and microplastics in three rivers in the Montesinho Natural Park and adjacent areas, Portugal. It investigated how intrapopulational ecological traits of the signal crayfish (Pacifastacus leniusculus), a non-native species widely distributed across Europe, may influence contaminant accumulation. Sampling was conducted at five sites along an invasion gradient (front-core), where macroplastics along the margins and signal crayfish were collected, followed by laboratory analyses for the morphological and polymeric characterization of the plastics. Chemical identification was performed using Fourier-transform infrared spectroscopy with attenuated total reflectance (FTIR-ATR) and Raman spectroscopy. Behavioural assays of boldness and aggressiveness were carried out on 100 captured signal crayfish individuals. Macroplastics were detected in all sampling sites. Microplastic abundance was higher at the invasion front, and the digestive tract contained significantly more particles than the gills, suggesting that the digestive tract is the primary route of exposure. No differences were detected between sex or individual size. Fibers were the dominant form, mainly in blue and black colors, and polymers such as polyethylene terephthalate (PET), polyethylene (PE), and polypropylene (PP) prevailed. Although personality traits differed between the invasion front and the core, with generally bolder and more aggressive individuals at the front, behavioural responses also showed sex-related patterns, with females tending to leave the shelter faster and males showing higher aggressiveness. However, no statistically significant correlations were found between animal personality and microplastic accumulation. Overall, our results indicate that plastic contamination depends on multiple factors arising from interactions between local environmental factors, including hydromorphological processes, and intrapopulational ecological traits (i.e., diet). This study highlights the importance of integrating behavioural analyses to better understand differential exposure to contaminants and their potential environmental implications for non-native species and possible legacy for native communities.

PMID:42348218 | DOI:10.1093/etojnl/vgag174

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Nevin Manimala Statistics

Medical Record Abstraction for Quality Improvement in Sepsis Care Using Artificial Intelligence: A Cluster Randomized Trial

JAMA Netw Open. 2026 Jun 1;9(6):e2611885. doi: 10.1001/jamanetworkopen.2026.11885.

ABSTRACT

IMPORTANCE: Hospital quality reporting remains a manual, costly process with critical limitations as a mechanism to improve care outcomes.

OBJECTIVE: To assess whether near-real-time quality measurement, enabled by large language models (LLMs), can improve quality performance as measured by the Centers for Medicare & Medicaid Services (CMS) Severe Sepsis and Septic Shock Management Bundle (SEP-1) quality metric.

DESIGN, SETTING, AND PARTICIPANTS: This single-blind, unstratified, cluster randomized trial was conducted between December 13, 2024, and July 8, 2025, at 2 academic emergency departments (EDs) within the University of California, San Diego (UCSD) health system. Participants included all 66 attending physicians who practiced in the UCSD EDs and worked more than 3 shifts per month prior to study initiation.

INTERVENTION: Participants were randomized to receive targeted feedback from LLM-determined compliance with SEP-1 at the time of patient discharge or standard process.

MAIN OUTCOMES AND MEASURES: The primary outcome was overall compliance with SEP-1. Secondary outcomes included expert agreement with the LLM SEP-1 determination, 30-day mortality, and intensive care unit admissions of patients with severe sepsis and/or septic shock in the ED. Effect sizes were estimated from a mixed-effects logistic regression model with the intervention group as a fixed effect and a random intercept for physician.

RESULTS: The study population included 66 physicians who treated 301 patients (121 in the control group and 180 in the intervention group; median age, 64.3 [IQR, 51.1-75.7] years; 171 [56.8%] male; 52 [17.3%] with chronic kidney disease; 52 [17.3%] with chronic heart failure) who met CMS inclusion criteria for SEP-1. Physicians in the control group had a SEP-1 compliance rate of 70.1%, while those in the intervention group had a rate of 82.9%. Assignment to the intervention group resulted in a 13.0% absolute improvement in SEP-1 compliance (95% CI, 2.5%-23.4%; odds ratio, 2.10 [95% CI, 1.15-3.81]; P = .02) in the mixed-effects model. The largest difference between the intervention group and control group was in noncompletion of the 30-mL/kg fluid bolus component (3 of 180 [1.7%] vs 16 of 121 [13.2%]), a documentation-sensitive component of the quality measure. Agreement between LLM determination and expert review was 92%. No significant differences existed in intensive care unit admissions or 30-day mortality.

CONCLUSIONS AND RELEVANCE: In this cluster randomized trial of artificial intelligence (AI)-enabled medical record abstraction for sepsis care, rapid assessment of SEP-1 performance and targeted feedback improved overall compliance with the measure. AI-driven quality clinical integration may address limitations in existing hospital quality reporting and better support a learning health system.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT07581340.

PMID:42348212 | DOI:10.1001/jamanetworkopen.2026.11885

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Needs and Perspectives on Upper Limb Prostheses Among Children and Adolescents With Upper Limb Differences

JAMA Netw Open. 2026 Jun 1;9(6):e2620122. doi: 10.1001/jamanetworkopen.2026.20122.

ABSTRACT

IMPORTANCE: In low- and middle-income countries (LMICs), limited access to adequate prosthetic care hinders the psycho-socio-motor development and educational progress of children and adolescents with upper limb differences. The suitability of current pediatric prosthetic solutions and the needs and expectations of children and adolescents with upper limb differences regarding upper limb prostheses (ULPs) remain understudied in LMICs.

OBJECTIVES: To examine and characterize the needs, expectations, and perceptions of Nigerian children and adolescents with upper limb differences regarding ULPs, assessing contextualized specifications for prosthetic development.

DESIGN, SETTING, AND PARTICIPANTS: This qualitative study was conducted from July 20 to July 23, 2024, in Lagos, Nigeria, among 25 children and adolescents with upper limb differences purposively selected from The IREDE Foundation prosthetic care program; recipients were aged 5 through 20 years who possessed at least 1 ULP. This study involved semistructured interviews and focus groups of Nigerian children and adolescents with upper limb differences. Transcripts were analyzed using thematic analysis between August 2024 and May 2025.

MAIN OUTCOMES AND MEASURES: The needs and perceptions of children and adolescents with upper limb differences regarding ULPs.

RESULTS: A total of 25 children and adolescents with upper limb differences (mean [SD] age, 13.5 [4.2] years; 15 male [60%]) enrolled in the study; 14 were interviewed, and 11 engaged in focus groups. The predominant cause of upper limb differences was traumatic amputations (16 [64%]), and the predominant level of upper limb differences was transhumeral (16 [64%]). Seven themes were identified from the interviews and focus groups. First, the children and adolescents with upper limb differences described the technical specifications of an ideal ULP by (1) highlighting the functionalities and task performance it should enable; (2) expressing their need for an active ULP and the characteristics of effective terminal devices; (3) specifying user-defined requirements for quality of prostheses components; (4) describing factors contributing to comfortable wear and use; and (5) explaining the necessity for anthropomorphism (shape and color) of ULP designs. Second, the psychosocial consequences of the conditions of the children and adolescents with upper limb differences and ULP use emerged: adverse repercussions (6) on self-concept and (7) in interactions with their social network, which were major factors in ULP acceptance. Overall, children and adolescents with upper limb differences expressed the need for an active, anthropomorphic, sturdy ULP, enabling them to actively engage with their peers.

CONCLUSIONS AND RELEVANCE: In this qualitative study, children and adolescents with upper limb differences expressed perceptions regarding their current ULP and described the requirements of prosthetic devices meeting the psychosocial and occupational needs within their socialcultural environment. Future studies could incorporate these findings into the development of environment-specific pediatric ULPs.

PMID:42348211 | DOI:10.1001/jamanetworkopen.2026.20122