Nevin Manimala

Stat Med. 2026 Jun;45(13-14):e70599. doi: 10.1002/sim.70599.

ABSTRACT

Progressive multi-state survival outcomes are common in trials with recurrent or sequential events and require treatment effect estimands that remain interpretable without proportional intensity or Markov assumptions. The restricted mean time in favor of treatment (RMT-IF) extends the restricted mean survival time to ordered multi-state processes and provides such an interpretable estimand. However, existing RMT-IF methods are nonparametric, assume covariate-independent censoring for independent observations, and do not accommodate cluster-randomized trials (CRTs), limiting both efficiency and applicability. We develop a class of doubly robust estimators for RMT-IF under right censoring using an augmented inverse-probability weighting framework that combines stage-specific outcome regression with arm-specific censoring models, yielding consistency when either nuisance model is correctly specified. We further extend the framework to CRTs by formalizing both cluster-level and individual-level average RMT-IF estimands to address informative cluster size and by constructing corresponding doubly robust estimators that account for within-cluster correlation. For inference, we employ model-agnostic jackknife variance estimators in both individually randomized and cluster-randomized settings. Extensive simulation studies demonstrate finite-sample performance, and the methods are illustrated using two randomized trial examples.

PMID:42186819 | DOI:10.1002/sim.70599

Alzheimers Dement. 2026 May;22(5):e71481. doi: 10.1002/alz.71481.

ABSTRACT

INTRODUCTION: The Dementia DataHub (DDH) reports U.S. dementia prevalence and incidence from Medicare data. Variation in sensitivity, specificity, and accuracy of diagnoses related to geography and participant characteristics complicates the interpretation of these data.

METHODS: We evaluated performance of DDH-defined Medicare claims diagnoses against linked Health and Retirement Study (HRS) survey-based dementia classifications.

RESULTS: DDH’s likely-or-higher dementia definition achieved 50% sensitivity, 97% specificity, and 91% accuracy relative to the HRS classification. Sensitivity, specificity, and accuracy varied across census divisions and by urbanicity. Respondents with dementia missed in claims were younger and healthier than those correctly identified.

DISCUSSION: Medicare claims reflecting diagnoses of dementia provide valuable information about who may be receiving dementia treatment and where; however, they often miss cases in ways that differ by geography and patient characteristics. Variation in diagnosis in Medicare claims relative to HRS survey-based dementia classification can be used to improve the value of Medicare diagnoses for surveillance purposes.

PMID:42186810 | DOI:10.1002/alz.71481

Circulation. 2026 May 26. doi: 10.1161/CIRCULATIONAHA.126.079484. Online ahead of print.

ABSTRACT

BACKGROUND: Catheter ablation for atrial fibrillation (AF) is one of the most common cardiovascular procedures being performed worldwide. Despite the large body of evidence of its effectiveness, with a single exception, prior ablation studies were largely unblinded trials. Accordingly, residual concerns remained about placebo effects, both for AF recurrence and, in particular, on subjective outcomes such as quality of life or anxiety. Here, we compared pulsed field ablation (PFA) with a sham procedure to treat patients with symptomatic AF.

METHODS: This prospective, sham-controlled, single-blind, randomized clinical trial with blinded end-point assessment enrolled patients with AF that was highly symptomatic (Atrial Fibrillation Effect on Quality-of-Life score <50). Patients were assigned 1:1 to PFA or a sham procedure. All participants received implantable cardiac monitors for continuous rhythm monitoring during follow-up. The 6-month co-primary outcomes were (1) time to first recurrence of atrial tachyarrhythmia and (2) changes from baseline in Atrial Fibrillation Effect on Quality-of-Life scores compared between groups. Secondary outcomes were AF burden and psychological distress (assessed by the Hospital Anxiety and Depression Scale [HADS]).

RESULTS: Patients (n=60) were randomized to PFA or sham. At 6 months, the first co-primary end point of AF recurrence was met in 2 patients (6.7%) who underwent PFA and 25 patients (83.3%) who underwent sham (posterior hazard ratio, 19.6 [95% bayesian credible intervals, 6.7-76.9]; posterior probability of superiority >0.99). For the second co-primary end point, Atrial Fibrillation Effect on Quality-of-Life scores showed greater improvement from baseline with PFA than sham (improved by 43.9+18.1 points versus 11.3+27.9 points; posterior median difference, 32.6 [95% bayesian credible interval, 20.2-44.9]; posterior probability of superiority >0.99). AF burden at 6 months was significantly lower in the PFA than the sham group (0 [0-0] versus 0.43 [0.04-3.47]; between group median difference, -0.39 [95% credible interval, -2.5 to -0.1], posterior probability of superiority >0.99). The Hospital Anxiety and Depression Scale score changed by -4 points (-7.8 to -2.0) with PFA and by -0.5 (-4.5 to 1.0) with sham (group median difference, -3.5 [95% credible interval, -6.0 to -1.0]; posterior probability of superiority >0.99).

CONCLUSIONS: In patients with AF, PFA was superior to sham in reducing arrhythmia recurrences and burden and improving quality of life and AF-associated psychological distress.

PMID:42186803 | DOI:10.1161/CIRCULATIONAHA.126.079484

COPD. 2026 May 11;23(1):2672702. doi: 10.1080/15412555.2026.2672702. Epub 2026 May 26.

ABSTRACT

Exacerbation of chronic obstructive pulmonary disease (ECOPD) frequently coexists with diabetes mellitus, creating competing priorities for respiratory stabilization and safe inpatient glycemic control. Evidence for an integrated, respiratory-endocrinology co-management pathway in this population remains limited. A total of 162 inpatients hospitalized with ECOPD and comorbid diabetes between January 1 and December 31, 2025 were randomly allocated to a respiratory-endocrinology multidisciplinary co-management pathway or usual care. The intervention comprised an ECOPD care bundle, protocolized glycemic management, pulmonary rehabilitation, and a structured discharge transition package. Primary outcomes were chronic airways assessment test (CAAT) and patient-day hyperglycemia/hypoglycemia. Secondary outcomes included length of stay, 30-day readmission, functional capacity assessed by the 1-min sit-to-stand (1-min STS) test (at discharge and 30 days), patient satisfaction (CSQ-8; at discharge and 30 days), and care-transition quality measured by the Care Transitions Measure-3 (CTM-3; at 7 and 30 days). Compared with usual care, co-management yielded clinically meaningful improvements in CAAT at discharge and at 30 days. Co-management reduced hyperglycemic patient-days (rate ratio 0.799) without an increase in mild, moderate or severe hypoglycemia. The intervention group also had a shorter length of stay, a lower 30-day readmission rate, higher CSQ-8 scores, higher CTM-3 scores, and greater 1-min sit-to-stand performance at discharge and 30 days. Findings were consistent in sensitivity analyses restricted to systemic corticosteroid recipients. A structured respiratory-endocrinology multidisciplinary co-management pathway improved ECOPD-related health status and inpatient glycemic safety while enhancing functional recovery, patient experience, and short-term utilization outcomes in hospitalized patients with ECOPD and diabetes.

PMID:42186793 | DOI:10.1080/15412555.2026.2672702

Addiction. 2026 May 26. doi: 10.1111/add.70474. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: With expanding cannabis legalization, normalization, and diversifying products and delivery methods in the United States (US), cannabis use disorder (CUD) prevalence is rising. Various modes of cannabis use may influence pharmacokinetics, usage patterns, and harm, affecting CUD risk. We measured associations between modes of cannabis use, including multi-modal patterns, and CUD prevalence and severity.

DESIGN AND SETTING: This cross-sectional study analyzed data from a nationally representative sample of US adults using the 2022-2023 National Survey on Drug Use and Health (NSDUH) data. Multivariable logistic regression analyses were employed to estimate the association between modes of cannabis use and past-year CUD, adjusting for potential confounders and covariates. Analyses were stratified by sex, age, and cannabis use frequency. Among multi-modal users, common combinations and their associations with CUD were further examined.

PARTICIPANTS/CASES: Respondents 18 years or older who reported past-year cannabis use (unweighted n = 25 549; weighted N = 58 850 309).

MEASUREMENTS: Exposure of interest was the mode of cannabis use, primarily categorized as smoke-only, vape-only, oral/mucosal-only, dab-only, topicals-only, and multi-modal (≥ two modes). The outcome variable was CUD in the past year, and CUD severity, based on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria. Covariates included age, sex, race/ethnicity, income, education, state cannabis law status, age of cannabis initiation, cannabis use motive, frequency of use, perceived risk of smoking cannabis, illicit drug use, past year mental illness, nicotine dependence, and alcohol use disorder.

FINDINGS: Of the total past-year cannabis users, 53.9% reported multi-modal cannabis use. Overall, CUD prevalence was 30.3%, ranging from 4.4% among oral/mucosal-only to 40.5% among multi-modal, and 28.9% among dab-only users (p < 0.0001). Moderate-to-severe CUD affected 13.2% of all users and was concentrated among multi-modal and dab-only users. In multivariable regression, multi-modal users had fourfold higher odds of CUD (adjusted odds ratio [AOR] = 4.14; 95% confidence interval [CI]: 2.91-5.90). Elevated odds were also observed among smoke-only (AOR = 2.98; 95% CI: 2.02-4.39) and vape/dab-only users (AOR = 1.89; 95% CI: 1.09-3.29), compared with oral/mucosal-only users. Analyses of multi-modal combinations showed the highest CUD odds among those using smoke + vape + oral/mucosal + dab (AOR = 19.74; 95% CI: 9.11-42.75), compared with oral/mucosal + topicals users.

CONCLUSIONS: In the United States, modes of cannabis use appear to be statistically significantly associated with prevalence and severity of cannabis use disorder, with multi-modal and inhaled routes conferring the greatest risk. Findings underscore the importance of considering mode of use alongside frequency and potency in clinical assessment, prevention, and policy strategies aimed at reducing cannabis-related harms.

PMID:42186749 | DOI:10.1111/add.70474

J Sleep Res. 2026 May 26:e70368. doi: 10.1111/jsr.70368. Online ahead of print.

ABSTRACT

Chronic spinal pain is associated with fragmented sleep, yet the neurophysiological mechanisms linking the two remain unclear. Given their role in sensory gating and sleep stability, sleep spindles may represent a key mechanism connecting chronic spinal pain and sleep fragmentation. This study examined whether pain intensity over the past 4 weeks was associated with sleep spindle density and related characteristics in individuals with chronic low back or neck pain and chronic insomnia disorder. Data from 120 participants, classified by self-reported pain severity (mild, moderate, severe), were compared on spindle density derived from C4-A1A2 and F4-A1A2 EEG channels. No significant group differences were found in spindle density (respectively, C4: p = 0.372 and F4: p = 0.744). Regression analyses adjusted for age, sex and medication use showed that pain intensity did not significantly predict spindle density (p > 0.05). However, exploratory regression models revealed small but statistically significant associations between pain intensity and both spindle power (p = 0.047) and amplitude (p = 0.038) on the C4 channel. These findings suggest that while spindle density does not vary meaningfully with pain intensity in this clinical population, alterations in spindle power and amplitude may reflect pain-related modulation of thalamocortical activity. This highlights the complexity of pain-sleep interactions in the presence of chronic spinal pain and insomnia. More nuanced, temporally resolved assessments of pain are needed to clarify the dynamic interactions between chronic pain, insomnia, and sleep microarchitecture.

PMID:42186730 | DOI:10.1111/jsr.70368

Chem Res Toxicol. 2026 May 26. doi: 10.1021/acs.chemrestox.6c00057. Online ahead of print.

ABSTRACT

Early warning systems (EWSs) are currently being developed by various authorities aiming at identifying potentially hazardous chemicals before they become a threat to the environment and human health. In this context, patents provide an excellent data source for exploring novel chemistry or the use of chemicals in materials and products. However, analysis of patents is challenging, including unraveling molecular structures presented as graphics depicting various elements, functional groups, and molecular bonds. Our study aims to improve EWS using automated artificial intelligence-based molecular structure recognition methods for encoding these for further hazard analysis. Current structure extraction tools are primarily trained on chemical structures collected from publicly available data sets, and the application of these tools to patent-specific chemical data has received little attention. This paper presents a field study utilizing the three tools Decimer, Molscribe, and Mathpix and assesses their performance in recognizing chemical structures in patents. Two data sets were compiled and curated including (1) diverse organic chemicals and (2) per- and polyfluoroalkyl substances (PFAS). It was revealed that these tools perform well on simpler molecular structures, whereas they struggle with more complex structural features, including repetitive units, cross-bonding, and Markush structures. Furthermore, it was discovered that these tools are extremely sensitive to image artifacts such as noise from lines and dots or distortions. Overcoming these challenges will be critical before implementation in automated EWS and thereby enable screening of patents for rapid and effective identification of potentially hazardous emerging chemicals.

PMID:42186716 | DOI:10.1021/acs.chemrestox.6c00057

Pulmonology. 2026 Dec;32(1):2671584. doi: 10.1080/25310429.2026.2671584. Epub 2026 May 26.

ABSTRACT

BACKGROUND: Respiratory syncytial virus (RSV) is an important cause of acute respiratory infection (ARI), but its burden in Portuguese adults remains under-investigated.

METHODS: This single-centre retrospective database cohort study examined RSV-ARI hospitalisations in adults aged ≥18 years over six consecutive seasons (2018/19 to 2023/24), a period which includes years impacted by COVID-19 disruptions. Outcomes included the prevalence of RT-PCR-confirmed RSV-ARI among tested ARI admissions, clinical features and adverse outcomes, healthcare resource use and direct costs; outcomes were also described for influenza-ARI to provide context. Analyses were descriptive without any comparison between the groups.

RESULTS: Of 7,125 ARI-hospitalisations 3,011 underwent RSV/influenza testing. The overall prevalence of RT-PCR-confirmed RSV-ARI and influenza-ARI in tested admissions was 8.1% and 20.3%, respectively. The study included 244 RSV-ARI and 612 influenza-ARI admissions, most ≥60 years old; 77.1% of RSV-ARI admissions and 61.4% of influenza-ARI admissions involved high-risk patients with comorbidities. Complications within 90 days were frequent, including acute cardiac events (RSV-ARI, 47.1%; influenza-ARI, 38.2%), respiratory failure (46.3% and 31.5%), pneumonia (34.0% and 22.4%) and acute renal disease (34.0% and 29.3%). All-cause in-hospital mortality was 19.7% for RSV-ARI (influenza-ARI, 12.8%). Mean length of stay for RSV-ARI was 8.5 days (interquartile range ([IQR], 9.7) with a mean cost of €4 757; for influenza-ARI, 7.4 days (IQR 8.9) and €3 537, respectively.

CONCLUSIONS: RSV represents an important cause of ARI-hospitalisation in older adults, especially in those with comorbidities, with a substantial clinical and economic burden, which was similar or higher than influenza (GSK study identifier: VEO-000773).

PMID:42186711 | DOI:10.1080/25310429.2026.2671584

JPEN J Parenter Enteral Nutr. 2026 May 26. doi: 10.1002/jpen.70106. Online ahead of print.

NO ABSTRACT

PMID:42186708 | DOI:10.1002/jpen.70106

J Periodontol. 2026 May 26. doi: 10.1002/jper.70145. Online ahead of print.

ABSTRACT

BACKGROUND: This study aimed to evaluate the impact of smoking on root coverage outcomes, comparing healing responses at 3-12 months following coronally advanced flap with a connective tissue graft (CAF+CTG).

METHODS: This prospective cohort study included 27 participants (13 smokers, 14 non-smokers) who required root coverage for a single Cairo Type 1 defect. Smoking status was biochemically verified (salivary cotinine). Clinical parameters, including recession depth and width, keratinized tissue width, and percentage of root coverage, were assessed at baseline, 3 months, and 12 months postoperatively. Statistical analysis employed both parametric and non-parametric tests to assess intra- and inter-group differences.

RESULTS: Compared with 3 months, both groups demonstrated increases in recession depth and decreases in percentage root coverage at 12 months. Median (interquartile range) recession depth increased from 1.0 (0.0-1.0) mm at 3 months to 1.0 (1.0-2.0) mm at 12 months in smokers, and from 0.0 (0.0-0.8) mm to 0.5 (0.0-1.0) mm in non-smokers. Root coverage percentage was significantly higher in non-smokers at 12 months, with 87.5% achieving root coverage compared with 66.6% in smokers (p = 0.024). Keratinized tissue width increased at 12 months, compared with 3 months, in both groups, from 5.08 ± 1.21 (mean ± SD) to 5.36 ± 1.80 mm and from 5.64 ± 1.59 to 5.77 ± 1.25 mm in smokers and non-smokers, respectively.

CONCLUSIONS: The negative impact of smoking on CAF+CTG outcomes became statistically detectable at 12 months postoperatively, a finding underscoring the need to consider smoking status when treatment planning and discussing expectations with patients.

PLAIN LANGUAGE SUMMARY: This study explored how smoking affects healing after a common gum surgery used to cover exposed tooth roots. We followed two groups of patients, smokers and non-smokers, for 1 year after they received the same treatment, which involved repositioning the gum and adding a tissue graft from the palate. At first, both groups showed good early healing, but differences emerged over time. By 12 months, smokers showed more return of gum recession and achieved less complete root coverage than non-smokers. Although most non-smokers maintained full coverage of the treated tooth, this was true for far fewer smokers. Both groups did show some healthy growth of the firm gum tissue around the tooth, but this did not offset the long-term disadvantage seen in smokers. These findings suggest that the harmful effects of smoking may not be obvious in the early months after surgery but become clearer as healing continues. Understanding this gradual difference can help dentists to guide patients more effectively, especially those who smoke, by setting realistic expectations and highlighting how smoking may limit the long-term success of treatment.

PMID:42186701 | DOI:10.1002/jper.70145