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Nevin Manimala Statistics

Transcutaneous auricular vagus nerve stimulation paired with task-specific training for improving walking and balance in chronic stroke: a double-blind, randomised controlled feasibility trial

J Neuroeng Rehabil. 2026 Jun 25. doi: 10.1186/s12984-026-01952-5. Online ahead of print.

ABSTRACT

BACKGROUND: Transcutaneous auricular vagus nerve stimulation (taVNS) paired with task-specific training has shown promise for improving upper-limb motor recovery after stroke but its effects on gait and balance remain unclear. This study evaluated the feasibility and safety of taVNS paired with task-specific training and explored preliminary effects on walking and balance outcomes in adults with chronic stroke.

METHODS: A double-blinded, sham-controlled trial was conducted to evaluate active versus sham taVNS paired with task-specific training (15 one-hour sessions over six weeks). Feasibility metrics included recruitment, participant experience, adverse events (AEs), and blinding effectiveness. Clinical outcomes (walking speed, endurance, gait parameters, and balance) were assessed at baseline, post-intervention, and ≥ 30 days post-intervention, supplemented by qualitative interviews.

RESULTS: Twenty-five adults with chronic stroke completed this study (18 males, mean age 64.99 ± 13.45 years; 41.80 ± 38.00 months post-stroke, 14 received active taVNS). Active taVNS was considered feasible and safe, with a 93% consent rate; 96% of participants found the intervention useful/helpful, and 100% found the stimulation acceptable. There were no serious AEs, with 16% of participants reporting mild side effects. Both groups improved across clinical outcomes. No statistically significant between-group differences were observed. Between-group effect sizes were small for gait, balance, disability, and self-efficacy, and small-to-moderate for walking endurance; however, confidence intervals crossed zero for all outcomes.

CONCLUSION: Active taVNS paired with task-specific training was feasible and well tolerated in chronic stroke. No definitive between-group effects were detected. Observed effect sizes should inform the design and sample size calculations of future adequately powered trials using optimised taVNS protocols.

PMID:42351122 | DOI:10.1186/s12984-026-01952-5

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Association between pre-existing sleep disorders and post-extraction discomfort in adult patients: a comparative study

BMC Oral Health. 2026 Jun 26. doi: 10.1186/s12903-026-09053-4. Online ahead of print.

ABSTRACT

BACKGROUND: Postoperative pain and discomfort following tooth extraction are common complications that may negatively affect patients’ quality of life. The potential association between pre-existing sleep disturbances and postoperative discomfort remains insufficiently explored.

OBJECTIVE: This study aimed to investigate the association between pre-existing sleep disturbances and postoperative pain intensity, emotional impact, and limitations in daily activities in patients undergoing routine tooth extraction.

MATERIALS AND METHODS: This retrospective observational cohort study included 111 adult patients (18-65 years) who underwent tooth extraction at Hacettepe University. Preoperative sleep quality was assessed using the Jenkins Sleep Scale (JSS). Participants were classified into two groups: Group A (patients with sleep disturbances; JSS ≥ 12, n = 48) and Group B (patients without sleep disturbances; JSS < 12, n = 63). Postoperative outcomes were evaluated on postoperative day 1 using the American Pain Society Patient Outcomes Questionnaire-Revised (APS-POQ-R). The null hypothesis stated that there would be no difference in postoperative discomfort between the two groups. Statistical analyses included the Mann-Whitney U test and Chi-square test.

RESULTS: Patients with pre-existing sleep disturbances (Group A) demonstrated significantly higher pain intensity scores (p < 0.001), greater emotional impact (p = 0.030), and increased limitations in daily activities (p = 0.002) compared with Group B. Satisfaction of pain management was significantly lower in Group A (p = 0.016). No statistically significant differences were observed between groups regarding nausea, numbness, itching, or dizziness (p > 0.05).

CONCLUSION: Pre-existing sleep disturbances were significantly associated with increased postoperative discomfort and reduced satisfaction following tooth extraction. The null hypothesis was rejected. However, given the observational design and the lack of predictive analysis, these results should be interpreted cautiously, and further prospective studies are needed before clinical application can be recommended.

PMID:42351121 | DOI:10.1186/s12903-026-09053-4

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Heterogeneous income gradients in early motherhood in Mexico: a population-based multi-method study, 2000-2020

Int J Equity Health. 2026 Jun 25. doi: 10.1186/s12939-026-02908-w. Online ahead of print.

ABSTRACT

BACKGROUND: Early motherhood remains a major public health and equity challenge in low- and middle-income countries, especially in Latin America. While poverty, education, gender norms, and barriers to sexual and reproductive health are well-established determinants, how household income translates into (or fails to translate into) delayed childbearing remains insufficiently understood-particularly in highly unequal settings marked by informality and fragmented social protection.

OBJECTIVE: To examine the association between household income and early motherhood in Mexico, and to disentangle direct and indirect socioeconomic pathways linking income to early childbearing.

METHODS: We conducted a population-based, multi-method analysis using harmonised municipal microdata from the 2000, 2010, and 2020 Mexican Population and Housing Censuses (n = 3.05 million women aged 12-24 years, representing 30.6 million individuals). Total household income was imputed using Quantile Random Forests trained on nationally representative income-expenditure surveys. Our analytical strategy combined: (1) machine learning models to identify key correlates and non-linear individual-level patterns of early motherhood; (2) Bayesian spatial models (INLA) to quantify subnational clustering and contextual heterogeneity; and (3) dynamic structural equation modelling to assess direct and lagged relationships among income, schooling-related indicators, union formation, and early motherhood outcomes.

RESULTS: Early motherhood prevalence declined modestly from 21.46% (2000) to 19.31% (2020) and remained concentrated in socioeconomically disadvantaged households. In individual-level models, marital status, age, household structure, and dependency ratio were the dominant correlates; income ranked eighth in feature importance. Partial dependence plots indicated a non-linear inverse L-shaped association: predicted risk increased up to approximately Int$ 1,760 (2018 PPP) per adult equivalent, then plateaued and declined slightly. Parity-specific models showed that income’s predictive relevance weakened with higher parity, with U-shaped patterns at the lowest income levels for second and ≥third births. Municipal analyses revealed persistent spatial clustering after adjustment for key predictors, and residual “place” effects consistent with unmeasured contextual constraints shaping early motherhood. In dynamic models, the direct income-early motherhood path was not statistically significant. Overall patterns were consistent with predominantly indirect linkages operating through schooling- and union-related indicators and reinforcing disadvantage dynamics at the municipal level.

CONCLUSIONS: In Mexico, early motherhood remains strongly shaped by intersecting social and territorial inequalities. Income gradients are modest and appear to operate mainly through schooling lag and union-formation pathways rather than as an isolated driver. Equity-oriented strategies are likely to be most effective when they integrate school retention, prevention of early unions, and youth-friendly sexual and reproductive health services, prioritising municipalities with persistently elevated risk.

PMID:42351120 | DOI:10.1186/s12939-026-02908-w

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Association of PAX1/JAM3 gene methylation, HR-HPV, and TCT with high-grade cervical lesions in a high-risk cohort: a multinomial logistic regression analysis

BMC Womens Health. 2026 Jun 25. doi: 10.1186/s12905-026-04622-9. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the risk factors associated with pathological progression of cervical lesions, specifically focusing on high-risk human papillomavirus (HR-HPV) infection, ThinPrep Cytologic Test (TCT), and PAX1/JAM3 gene methylation in a high-risk colposcopy-referred cohort.

METHODS: A total of 409 patients who underwent colposcopy-directed biopsy at the First Hospital of Hebei Medical University between January, 2023 and April, 2025 due to abnormal TCT results, HR-HPV infection, or positive PAX1/JAM3 gene methylation were analyzed. The sensitivities of different methods were compared, and unordered multivariate logistic regression was used to analyze the risk factors for high-grade cervical lesions and pathological progression.

RESULTS: Univariate analysis demonstrated that age, gravidity, age at first sexual intercourse, number of sexual partners, menopausal status, HR-HPV infection, TCT results, and PAX1/JAM3 methylation were significantly associated with pathological grade (all P < 0.05). In the multinomial regression analysis, compared to the inflammation group, both other high-risk HPV (OR = 3.930) and very-high-risk (16/18) HPV infections (OR = 3.725), as well as non-NILM TCT (OR = 2.435), were significantly associated with an increased risk of LSIL. For the progression to HSIL, very-high-risk HPV (OR = 6.801), non-NILM TCT (OR = 2.399), positive PAX1 methylation (OR = 4.145), and positive JAM3 methylation (OR = 8.215) were identified as strong independent risk factors.

CONCLUSION: In a high-risk colposcopy-referred cohort, HR-HPV infection, non-NILM TCT results, and positive PAX1/JAM3 gene methylation are independently associated with the presence of high-grade cervical lesions. These biomarkers have the potential to enhance clinical risk stratification and inform decision-making in cervical cancer screening. However, their clinical utility and cost-effectiveness need to be further evaluated through larger, prospective studies to validate their role in routine clinical practice.

PMID:42351112 | DOI:10.1186/s12905-026-04622-9

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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