Nevin Manimala

Am J Physiol Heart Circ Physiol. 2026 Jul 30. doi: 10.1152/ajpheart.00036.2026. Online ahead of print.

ABSTRACT

Background: Arterial waveforms are altered in left ventricular systolic dysfunction. We aimed to investigate the diagnostic implications of automatically analyzed pressure waveforms and their changes over time in patients with reduced ejection fraction. Methods: Arterial waveforms were recorded non-invasively using applanation tonometry in patients with heart failure with reduced ejection fraction (HFrEF) and in matched controls. Waveform parameters were analyzed with respect to the left ventricular ejection time index (LVETi), the characteristics of antegrade and reflected waves, their interaction as quantified by the Augmentation Index (AIx), and wave intensity, expressed as the ratio of the S and D peak intensities (SDR). Results: Overall, 78 HFrEF patients (ejection fraction (EF) 28+/-9%) and 78 controls (EF 66+/-8%), matched for sex, age, presence of hypertension and diabetes, systolic and diastolic blood pressure, and heart rate were included. All waveform parameters were statistically different between patients and controls. In ROC analysis, HFrEF patients and controls could be separated best using LVETi (AUC 0.897, p<0.0001) and SDR (AUC 0.911, p<0.0001). In newly diagnosed and treated HFrEF patients, the AUC for discrimination between HFrEF patients from controls was almost ideal (0.978, p<0.0001), when a combination of LVETi and SDR was used. Finally, in 46 HFrEF patients with available follow up data, concordance analysis showed a high agreement of up to 0.8 between changes in the cardiac function (eg., using EF) and changes in several waveform parameters. Conclusions: Pulse waveform parameters may be useful for screening and follow-up of patients with HFrEF.

PMID:42531502 | DOI:10.1152/ajpheart.00036.2026

JMIR AI. 2026 Jul 30;5:e90590. doi: 10.2196/90590.

ABSTRACT

BACKGROUND: Synthetic electronic health record generation is limited not only by statistical fidelity but also by clinical validity. Records that appear statistically plausible may still violate hard structural, physiological, or relational constraints.

OBJECTIVE: This study evaluated best-of-N constraint-minimizing selection as an inference-time strategy for improving clinical validity and characterized when such selection succeeds or fails as a function of the generator’s valid support mass (pvalid).

METHODS: We evaluated Wasserstein generative adversarial network with gradient penalty (WGAN-GP) and conditional tabular generative adversarial network (CTGAN) on 3 public clinical tabular datasets: stroke prediction (n=5110), diabetes health indicators (n=100,000), and cardiovascular disease (n=68,599). For each generator, we compared random sampling, naive clipping, and best-of-N selection (N ∈ {8, 16, 128}). Validity was assessed via dataset-specific rule violations; fidelity via Kolmogorov-Smirnov (KS) statistics and correlation preservation; utility via TSTR (train-on-synthetic-test-on-real) AUC (area under the receiver operating characteristic curve); and privacy via membership inference attack (MIA) AUC and distance to closest record (DCR).

RESULTS: Best-of-N effectiveness was governed by the base generator’s valid support mass. In stroke, WGAN-GP had pvalid=0, and all selection strategies, including strict rejection across 5000 draws, produced 500/500 (100%) invalid samples. In cardiovascular data, WGAN-GP had pvalid=0.12; best-of-16 reduced violations from 441/500 (88.2%) to 65/500 (13.0%), and best-of-128 eliminated them entirely (0/500), matching theoretical predictions exactly. In diabetes, WGAN-GP random sampling was already fully valid (0/500 violations), and best-of-N primarily shifted utility. Across all 3 datasets, CTGAN+best-of-16 achieved 0/500 violations with strong fidelity (mean KS≤0.12) and utility (TSTR AUC up to 0.81). MIA AUC remained near-random guessing (approximately 0.50) throughout, though DCR-based proximity concentration increased markedly under CTGAN selection (reaching 22.6% on stroke and 100% on cardiovascular data).

CONCLUSIONS: Best-of-N functions as a bounded-budget feasibility filter rather than a universal repair mechanism. Its effectiveness depends critically on the generator’s valid support mass. CTGAN+best-of-16 offered the strongest overall trade-off across clinical validity, fidelity, utility, and privacy in our experiments.

PMID:42531495 | DOI:10.2196/90590

Womens Health (Lond). 2026 Jan-Dec;22:17455057261474450. doi: 10.1177/17455057261474450. Epub 2026 Jul 30.

ABSTRACT

IntroductionRepeated induced abortion is an important public health concern globally. While its burden spans both developed and developing contexts, complications are disproportionately higher in low-resource settings.ObjectiveTo assess the prevalence and associated factors of repeated induced abortion among women seeking abortion care services in public hospitals in Northwest Ethiopia.Study DesignAn Institutional based cross-sectional study was employed.MethodsThe study was conducted among 406 systematically selected women seeking abortion care between April 10 and June 15, 2022. Data were collected using interviewer-administered questionnaires via EpiCollect. Analysis was performed using SPSS version 25. Binary logistic regression was utilized to identify potential factors influencing the outcome variable. Odds ratios with their 95% confidence intervals were used to determine the strength of association and variables with a p-value below 0.05 were considered statistically significant factors for the outcome variable. Reporting follows the Strengthening the Reporting of Observational Studies in Epidemiology statement.ResultsOf the 406 participants 21.9% (95% CI: 18.1-26.1) reported repeated induced abortion. Age ≥ 30 years (adjusted odds ratio (AOR) = 5.505; 95% CI: 1.279-23.696), having multiple sexual partner (AOR = 5.148; 95% CI: 2.410-10.997), and alcohol consumption (AOR = 2.535; 95% CI: 1.033-6.218) were the significant factors associated with repeated induced abortion.ConclusionApproximately one in five women seeking abortion care reported a lifetime history of repeat induced abortion. Rather than relying on uniform approaches, it is crucial to implement tailored counseling and behavioral assessments that focus specifically on older women, those with multiple sexual partners, and women who consume alcohol, as these subgroups exhibit significantly higher odds of repeat induced abortion.

PMID:42531481 | DOI:10.1177/17455057261474450

ESC Heart Fail. 2026 Jul 30:xvag209. doi: 10.1093/eschf/xvag209. Online ahead of print.

ABSTRACT

BACKGROUND: Two baseline 6-minute walk tests (6MWTs) have been recommended to mitigate a potential learning effect when assessing exercise performance, but the magnitude of any learning effect in heart failure with reduced ejection fraction (HFrEF) is uncertain. Using the Sildenafil in Heart Failure (SilHF) trial, in which two baseline 6MWTs were performed (screening and inclusion), we assessed a potential learning effect in this population. We also assessed whether choice of baseline test affected associations with longitudinal patient-reported outcomes and compared our findings to reports in the current literature.

METHODS AND RESULTS: In SilHF, 69 patients with HFrEF and evidence of pulmonary hypertension performed 6MWTs at screening and again at study inclusion. Tests were performed no more than two weeks apart on unchanged optimal medical therapy. Only the inclusion 6MWT was used for efficacy evaluation of sildenafil. Screening and inclusion distances were compared using a paired t-test. Additionally, we assessed whether each baseline 6MWT (screening and inclusion) correlated with longitudinal patient-reported outcome measures. Outcomes included the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the EuroQoL-5D visual analogue scale (EQ-5D VAS), assessed at 24 weeks. Although the inclusion 6MWT distance was statistically significantly higher than the screening test (+11.3 m, 95% CI 2.6 to 20.1, p = 0.012), the two baseline tests demonstrated very similar correlation coefficients with longitudinal patient-reported outcomes.

CONCLUSION: We observed a small increase in 6MWD between repeat baseline tests, consistent with a modest learning effect that is unlikely to be clinically meaningful. Both initial 6MWTs showed similar significant correlations with other longitudinal patient-reported outcome measures. In symptomatic HFrEF with pulmonary hypertension, a single baseline 6MWT may be sufficient to assess functional capacity.

PMID:42531461 | DOI:10.1093/eschf/xvag209

Can Urol Assoc J. 2026 Jul 20. doi: 10.5489/cuaj.9576. Online ahead of print.

ABSTRACT

INTRODUCTION: A delay beyond 12 weeks from diagnosis to radical cystectomy (RC) is considered to impart worse oncologic outcomes for patients with muscle-invasive bladder cancer (MIBC); however, no randomized clinical trials have examined this question. We therefore emulated a hypothetical target clinical trial using contemporary data to evaluate the association between time from diagnosis to RC and oncologic outcomes.

METHODS: We conducted observational analyses using the National Cancer Database from 2006-2015 to emulate a hypothetical target trial in adults aged 40-79 years with incident cT2-4 N0 M0 urothelial carcinoma of the bladder, treated with RC from 4-18 weeks after diagnosis. We evaluated the association of late RC with pathologic upstaging at RC and overall survival (OS) and conducted exploratory analyses evaluating the association of time to RC with each outcome modeled flexibly.

RESULTS: A total of 3747 patients were included, of which 2992 underwent early RC. Median followup was 32.2 months. In adjusted analyses, late RC was not associated with an increased risk of pathologic upstaging compared to early RC. In addition, there was no statistically significant difference in adjusted OS for late and early RC, respectively. Similar findings were observed across categories of cT stage, age, Charlson index, and gender.

CONCLUSIONS: In observational analyses designed to emulate a hypothetical target trial of early vs. late RC, the timing of RC was not associated with a statistically significant increase in pathologic upstaging or a difference in OS when performed from 4-18 weeks after diagnosis. These results suggest the need to re-examine the traditional recommendations for timing of RC following diagnosis.

PMID:42531446 | DOI:10.5489/cuaj.9576

Can Urol Assoc J. 2026 Jul 20. doi: 10.5489/cuaj.9584. Online ahead of print.

ABSTRACT

INTRODUCTION: Urology training programs internationally have adopted robotic surgery, particularly robotic prostatectomy. We aimed to determine the knowledge gap in the understanding of robotic prostatectomy for residents compared to urologists, as there is a need for dedicated robotic training curricula.

METHODS: A 16-question survey was developed, documenting the difference in understanding between residents and urologists. The survey contained items pertaining to patient anatomy, procedural steps, and surgical decision-making. The survey was completed immediately following a robotic prostatectomy by both the urology resident performing the bedside assistance, and the urologist. Statistical analysis of the quantitative questions was performed using kappa scores, and thematic analysis was performed to analyze the qualitative responses.

RESULTS: Forty-two surveys were administered to urology residents and urologists at The Ottawa Hospital over 10 weeks. Disagreements were identified between urology resident and urologist responses. This was noted with the comparison of the following procedural steps: vesicourethral anastomosis (kappa 0.138), apical dissection (kappa 0.149), and seminal vesicle dissection (kappa 0.342). The qualitative responses found discrepancies between resident and urologist understanding. When asked to describe challenges during the procedure, urologists described causal factors leading to challenges and how to manage these issues intraoperatively. In contrast, the residents’ responses focused on readily visible aspects of the procedure, including bleeding or difficult exposure, omitting to describe the cause of these challenges.

CONCLUSIONS: There is a gap in urology resident knowledge and understanding of a robotic prostatectomy. This information is key to expand the understanding of robotic prostatectomy surgical decision-making and its training.

PMID:42531444 | DOI:10.5489/cuaj.9584

J Asthma. 2026 Jul 30:1-18. doi: 10.1080/02770903.2026.2712839. Online ahead of print.

ABSTRACT

BACKGROUND: Smoking relapse is prevalent, yet its long-term association with incident asthma remains underexplored. Repeated quit-relapse cycles may exacerbate airway inflammation more acutely than steady-state smoking. We investigated the association between smoking-relapse trajectories and incident asthma risk using a nationally representative longitudinal dataset.

METHODS: We analyzed 10-year data (2009-2018) from the Korea Health Panel Survey for 16,240 adults without baseline asthma. Participants were classified into five trajectories: non-smokers (NS), successful quitters without relapse (SQ-), successful quitters with relapse (SQ+), unsuccessful quitters with relapse (UQ+, chronic relapsers), and always smokers (AS). Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for incident asthma (ICD-10 J45-J46).

RESULTS: During the 10-year follow-up, 159 incident asthma cases were identified. Compared to NS, chronic relapsers (UQ+) exhibited the highest risk (aHR 3.81; 95% CI 1.84-7.91), followed by SQ- (aHR 2.54; 95% CI 1.30-4.96) and AS (aHR 2.25; 1.08-4.71). While UQ + showed a higher point estimate than AS, the difference was not statistically significant. Other significant risk factors included age ≤65 years, Medical Aid enrollment, and higher comorbidity scores.

CONCLUSIONS: Smoking-relapse trajectories, particularly chronic relapse, are associated with an elevated risk of incident asthma. These findings should be interpreted as hypothesis-generating and require confirmation in independent cohorts.

PMID:42530977 | DOI:10.1080/02770903.2026.2712839

J Int Med Res. 2026 Jul;54(7):3000605261469014. doi: 10.1177/03000605261469014. Epub 2026 Jul 30.

ABSTRACT

ObjectiveThe potential causal role of molecular biomarkers of biological aging in osteoporosis remains uncertain. This study aimed to evaluate whether genetically predicted levels of aging-related traits are causally associated with the risk of osteoporosis.MethodsIn this study, we selected eight exposures: telomere length, mitochondrial DNA copy number, insulin-like growth factor 1 levels, DNA methylation PhenoAge acceleration, leucine, isoleucine, valine, and Dickkopf-related protein 1. A bidirectional two-sample Mendelian randomization analysis was conducted among the European population. The inverse-variance weighted method served as the primary analysis, complemented by Mendelian randomization-Egger, weighted median, mode-based methods, Cochran’s Q test, the Mendelian randomization-Egger intercept, and leave-one-out analysis to assess robustness, heterogeneity, and pleiotropy.ResultsThe inverse-variance weighted analysis showed nominal associations (p < 0.05) between genetically predicted higher insulin-like growth factor 1 (odds ratio = 0.910, 95% confidence interval: 0.840 to 0.985, p = 0.019) and isoleucine (odds ratio = 0.780, 95% confidence interval: 0.618 to 0.984, p = 0.036) with a lower risk of osteoporosis and elevated Dickkopf-related protein 1 (odds ratio = 1.195, 95% confidence interval: 1.043 to 1.368, p = 0.010) with a higher risk of osteoporosis; however, none remained significant after Bonferroni correction (p > 0.00625). Sensitivity analyses suggested a statistically significant association for Dickkopf-related protein 1 (weighted median and mode, p < 0.00625), whereas no significant causal effects were observed for any of the other biomarkers. Reverse Mendelian randomization revealed no evidence that osteoporosis influenced any of the biomarkers.ConclusionsIn this study, no robust causal effects were identified between the eight aging biomarkers and osteoporosis in the European population. However, the nominal associations observed for insulin-like growth factor 1, isoleucine, and Dickkopf-related protein 1 warrant further investigation into the aging-skeleton axis.

PMID:42530965 | DOI:10.1177/03000605261469014

Stat Methods Med Res. 2026 Jul 30:9622802261468019. doi: 10.1177/09622802261468019. Online ahead of print.

ABSTRACT

In lifetime studies, a proportion of subjects may never experience the event of interest, giving rise to the notion of cure rate. While traditional cure models address this in univariate set-up, many applications involve paired lifetimes, such as twin survival studies, paired organs, or dependent components in a system. In such cases, both the possibility of cure in one or both marginals and the dependence between lifetimes need to be modeled simultaneously, motivating bivariate cure models. We propose here a flexible framework for analyzing bivariate cure data by combining parametric modeling of each marginal survival distribution with a shared frailty term for capturing dependence. The shared frailty is assumed to follow a generalized gamma distribution, providing substantial flexibility in representing diverse dependence structures induced by unobserved frailty. This formulation accommodates cured individuals in one or both marginals and captures the joint survival dynamics of susceptible pairs. Likelihood-based inference for the proposed model is then developed, with estimation carried out using the expectation-maximization algorithm. The performance of the model and the associated inferential method are then evaluated through extensive simulation studies, demonstrating the efficiency and accuracy in estimating model parameters. A real data application, concerning diabetic retinopathy, further illustrates how the model provides insights into cure dynamics and associations that will not be evident in univariate analyses. The proposed bivariate cure model offers a comprehensive statistical tool for jointly studying cure fractions and survival dependence in paired lifetime settings, broadening the applicability of cure rate methodology in biomedical research.

PMID:42530958 | DOI:10.1177/09622802261468019

JAMA Ophthalmol. 2026 Jul 30. doi: 10.1001/jamaophthalmol.2026.2767. Online ahead of print.

ABSTRACT

IMPORTANCE: Whether prior pars plana vitrectomy (PPV) independently increases the risk of cystoid macular edema (CME) following cataract surgery remains unknown.

OBJECTIVE: To evaluate associations between prior PPV and incidence of CME after cataract surgery.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was conducted using the TriNetX US Network, a multicenter federated electronic health record network from December 2005 to December 2025 including academic and community hospitals in the US. Adults aged 18 years or older who underwent cataract surgery were categorized into those with vs those without a history of PPV (≥6 months prior to cataract surgery), excluding those with preexisting CME or risk factors for CME. Data were analyzed from December 2025 through January 2026.

EXPOSURE: History of PPV performed more than 6 months prior to cataract surgery.

MAIN OUTCOMES AND MEASURES: The primary outcome was the incidence of CME within 30 to 90 days postoperatively, identified by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnostic codes. Risk ratios (RR) were used to compare outcomes. Propensity score matching was performed for demographic and clinical covariates (age, sex, race, hypertension, hyperlipidemia, diabetes, myopia, retinal detachment [RD] history).

RESULTS: After propensity score matching with 615 983 patients undergoing cataract surgery, 7422 patients had a prior PPV. After propensity score matching, among patients with prior PPV, mean (SD) age was 62.0 (11.6) years, and 3623 patients (49.5%) were female; among the non-PPV group, mean (SD) age was 61.9 (12.2) years, and 3625 patients (49.5%) were female. Among 14 636 patients representing 7318 propensity score-matched pairs, CME occurred in 336 of 7318 patients with prior PPV (4.59%) compared with 90 of 7318 non-PPV controls (1.23%) (difference, 3.36%; 95% CI, 2.82%-3.90%; RR, 3.73; 95% CI, 2.97-4.70; P < .001). Elevated CME risk persisted in subgroup analyses evaluating prior PPV for RD (5.65% vs 1.22%; absolute difference, 4.43%; 95% CI, 3.48%-5.38%; RR, 4.62; 95% CI, 3.20-6.67; P < .001), as well as those for non-RD indications (3.99% vs 1.23%; absolute difference, 2.76%; 95% CI, 2.06%-3.48%; RR, 3.26; 95% CI, 2.36-4.50; P < .001). Furthermore, after excluding patients with intraoperative and postoperative complications of cataract surgery, the prior PPV group was still found to have a higher risk of CME (4.59% vs 1.26%; absolute difference, 3.32%; 95% CI, 2.77%-3.88%; RR, 3.63; 95% CI, 2.88-4.58; P < .001).

CONCLUSIONS AND RELEVANCE: Results of this cohort study suggest that eyes with vs without prior PPV have higher incidences of postoperative CME. However, numerous limitations, including dependence on coding-based diagnoses and lack of visual acuity outcomes, preclude determining the role of prophylaxis or monitoring for CME in vitrectomized eyes undergoing cataract extraction.

PMID:42530955 | DOI:10.1001/jamaophthalmol.2026.2767