Publications by Year: 2026

We develop methods to analyze clustered competing risks data when the event types are only available in a training dataset and are missing in the main study. We propose to estimate the exposure effects through the cause-specific proportional hazards frailty model where random effects are introduced into the model to account for the within-cluster correlation. We propose a weighted penalized partial likelihood method where the weights represent the probabilities of the occurrence of events, and the weights can be obtained by fitting a classification model for the event types on the training dataset. Alternatively, we propose an imputation approach where the missing event types are imputed based on the predictions from the classification model. We derive the analytical variances, and evaluate the finite sample properties of our methods in an extensive simulation study. As an illustrative example, we apply our methods to estimate the associations between tinnitus and metabolic, sensory and metabolic+sensory hearing loss in the Conservation of Hearing Study Audiology Assessment Arm.

ObjectivesTetralogy of Fallot (TOF) repair is associated with low mortality in high-performance centers, but outcomes are worse in low- and middle-income countries (LMICs). Prior studies have not demonstrated a strong link between Technical Performance Score (TPS) and mortality. The aim of this was to evaluate risk factors for mortality and complications after TOF repair in a high-volume LMIC heart center with a focus on surgical performance.MethodsWe retrospectively reviewed children undergoing TOF repair between 2015 and 2022. Patients over two years of age or with complex defects beyond atrial septal defect and persistent ductus arteriosus were excluded. Preoperative factors included age, weight, genetic syndromes, urgency, and pulmonary artery z-scores. Intraoperative variables included transannular patch use, cardiopulmonary bypass and cross-clamp times, surgeon, and TPS classification. Postoperative variables included delayed sternal closure (DSC), extracorporeal membrane oxygenation (ECMO), and Vasoactive Inotropic Score (VIS) during the first 24 h. Outcomes included mortality, complications, and length of stay (LOS). Analyses included logistic regression and Kaplan-Meier estimates.ResultsAmong 255 patients, in-hospital mortality was 7.5% (n = 19). Technical Performance Score class 3 was an independent predictor of mortality (P = .027), along with VIS 24 h and ECMO. Cardiopulmonary bypass time, ECMO, and DSC were associated with major complications. Technical Performance Score class 3 correlated with longer LOS, but multivariable analysis identified low weight and ECMO as independent LOS predictors. Five-year survival was worse in TPS class 3 (P = .007).ConclusionsInadequate TPS is an independent predictor of mortality after TOF repair in an LMIC context. Class 3 TPS also relates to longer hospitalization and worse medium-term survival. Surgical quality remains essential for better outcomes.

Cardiopulmonary vascular diseases are the leading cause of death worldwide. Metabolic reprogramming and inflammation are 2 commonly shared hallmarks of such diseases. The bifunctional enzymes PFKFB (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases) 1 to 4 are well-known for their critical functions in glucose metabolism. Emerging evidence has indicated that PFKFB enzymes, particularly PFKFB3, are essential immunometabolic regulators and implicated in cardiopulmonary vascular and other pathologies. We here first summarize the structural basis for the catalytic function of PFKFB family enzymes, introduce the recent advances on the regulation of PFKFB3 expression and activity as well as its nonmetabolic functions, then elaborate on how dysregulation of PFKFBs influences physiological and pathological states of the cardiovascular and pulmonary systems, and finally touch on the current development of pharmacological inhibitors of PFKFB3 as potential therapeutics.

PURPOSE: The DANFLU-1 trial suggested lower incidence of hospitalizations for pneumonia and influenza, respiratory disease and all-cause mortality among older adults receiving high-dose (HD-IV) versus standard-dose (SD-IV) influenza vaccine. This study assessed the relative effectiveness of HD-IV versus SD-IV according to comorbidity in elderly individuals.

METHODS: This was a post-hoc analysis of the DANFLU-1 randomized controlled feasibility trial of HD-IV versus SD-IV conducted during the 2021-2022 influenza season in adults aged 65-79 years. Outcomes assessed included influenza-related, respiratory, and cardiovascular hospitalizations, and mortality. We tested for effect modification by level of the Charlson Comorbidity Index (CCI) using ICD-10 codes up to 10 years prior to randomization.

RESULTS: Of the 12,477 randomly assigned participants (mean age 71.7 ± 3.9 years, 47.1% female), 8,020 (64.3%) had CCI = 0, 3,560 (28.5%) had CCI = 1-2 and 893 (7.2%) had CCI ≥ 3. When comparing HD-IV with SD-IV, hazard ratios of hospitalizations for pneumonia and influenza were similar across CCI groups (HR [95%CI]: 0.15 [0.03-0.68] for CCI = 0, 0.36 [0.11-1.15] for CCI = 1-2, 1.00 [0.25-4.00] for CCI ≥ 3). Comparable patterns were found for hospitalizations for respiratory disease (0.46 [0.17-1.20] for CCI = 0, 0.67 [0.32-1.39] for CCI = 1-2, 0.66 [0.24-1.87] for CCI ≥ 3) and all-cause mortality (0.28 [0.09-0.86] for CCI = 0, 0.70 [0.30-1.63] for CCI = 1-2, 0.57 [0.24-1.36] for CCI ≥ 3). There was no statistical evidence of effect modification by CCI for any outcome.

CONCLUSIONS: The lower incidences of clinical outcomes for HD-IV compared to SD-IV were not significantly modified by CCI. The potential benefit of HD-IV versus SD-IV may therefore be applicable regardless of comorbidity burden. Further research is required to confirm these findings.

BACKGROUND: Prescription depressants, particularly benzodiazepines, gabapentinoids, and Z-drugs, pose overdose risk. Understanding their prevalence in overdose fatalities and co-involved substances is critical.

OBJECTIVE: To identify latent substance classes in prescription depressant-involved overdose deaths.

DESIGN: Retrospective cohort study PARTICIPANTS: All individuals whose fatal overdoses involved prescription depressants from 2000-2023 in Massachusetts, US (n = 8,665).

MAIN MEASURES: Data were obtained from the Massachusetts Registry of Vital Records and Statistics. Substances were identified using ICD-10 codes. Literal text entries were available from 2015-2023. We conducted a latent class analysis to derive substance classes and a multinomial logistic regression to examine associated factors. We assessed the proportion of deaths these classes comprised over time.

KEY RESULTS: Five latent classes emerged and were characterized based on the substances with highest conditional probabilities within and across classes: 1) antidepressants (21.2%); 2) fentanyl, cocaine, and benzodiazepines (34.4%); 3) antidepressants and antipsychotics (8.2%); 4) prescription opioids and benzodiazepines (19.5%); and 5) fentanyl and gabapentin or xylazine (16.7%). Over time, fentanyl-related classes came to dominate earlier prescription-only classes; deaths in Class 1 declined by 86.5%, while those in Class 5 rose from 9.6% to 45.1%. Compared to Class 2, all other classes were older, more likely female, married, educated, from rural areas, and overdosed at home. Classes 1, 3, and 5 were more likely non-White.

CONCLUSIONS: Thousands of Massachusetts overdose deaths have involved prescribed medications, suggesting missed opportunities for intervention. Over time, the demographic patterns of deaths involving antidepressants, antipsychotics, benzodiazepines, and prescription opioids persisted, reflecting longstanding trends in polypharmacy among older women and racial disparities in prescribing. Prescription monitoring, deprescribing, screening for illicit drug use, and discussion of diversion risks are all needed. Findings underscore the need for clinical and policy interventions to reduce overdose risks among women, older individuals, and racial minorities.

In this article, we present eight studies published in the last 2 years that are likely to influence the practice of general practitioners in 2026. The key messages highlight the effectiveness of metformin for knee pain treatment, recent advances in the management of poorly controlled asthma, and the absence of contraindications to administering influenza and Covid-19 vaccines simultaneously. In addition, several articles describe the association between sleep duration and hypertension, blood pressure measurement protocols, the effects of vitamin K2 on nocturnal leg cramps, and the effects of intermittent fasting on weight loss. Finally, the Thrombosis Risk Prediction in Patients with Cast Immobilization Score can be used to assess whether therapeutic anticoagulation is indicated in cases of lower-limb immobilization.

IMPORTANCE: Potentially inappropriate medications are commonly overprescribed to older adults. Although electronic health record (EHR)-based tools can increase use of evidence-based medications, their ability to reduce prescription of potentially inappropriate medications remains unclear.

OBJECTIVE: To test the effects of 2 EHR interventions, designed using behavioral science techniques, on the deprescribing of potentially inappropriate medications compared with usual care in older patients.

DESIGN, SETTING, AND PARTICIPANTS: In this 3-group parallel randomized clinical trial, 201 primary care physicians (PCPs) in an academic center in Massachusetts were cluster-randomized in November 2022. Follow-up ended March 15, 2024. The intervention focused on patients of randomized PCPs who were 65 years or older, had a PCP visit between November 10, 2022, and March 15, 2024, and were prescribed at least 90 pills of benzodiazepines, nonbenzodiazepine sedative hypnotics, or at least 2 anticholinergic medications in the past 180 days.

INTERVENTIONS: PCPs were randomized to usual care (no intervention) or to 1 of 2 sequential EHR interventions: a precommitment intervention, in which an EHR message was sent to the physician during the first patient visit asking the PCP to initiate deprescribing discussions with a second reminder EHR message at the patient's second visit encouraging deprescribing; and a boostering intervention, in which PCPs received a notification encouraging deprescribing at the first patient visit and an in-basket reminder 4 weeks later.

MAIN OUTCOMES AND MEASURES: The primary outcome was deprescribing at least 1 medication on or after the first patient visit though the end of follow-up. Deprescribing was defined as physician-directed discontinuation or medication tapering assessed at the patient level using EHR data. Generalized estimating equations with a log link and binary-distributed errors were used for analyses, adjusting for clustering and multiple testing using Holm-Bonferroni corrections.

RESULTS: Of 1146 participants (mean age, 73.6 years [SD, 6.4]; 69.7% female, mean follow-up, 289.9 days), 373 (32.5%) had at least 1 medication deprescribed: 145 (36.8%) in the precommitment group, 122 (34.3%) in the boostering group, and 106 (26.8%) in usual care. Compared with usual care, deprescribing was 40% more likely (relative risk [RR], 1.40; 95% CI, 1.14-1.73; absolute difference, 10.4%) in the precommitment group and 26% more likely (RR, 1.26; 95% CI, 1.01-1.57; absolute difference, 6.5%) in the boostering group. No serious adverse events were reported through the adverse event reporting system. Death rates based on manual chart review were 1.4% in the precommitment group, 3.9% in the boostering group, and 1.8% in the usual care group.

CONCLUSIONS AND RELEVANCE: These results support use of EHR tools designed using behavioral science principles to significantly increase rates of deprescribing potentially inappropriate medications used by older adults.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT005538065.

OBJECTIVE: Group-based posttraumatic stress disorder (PTSD) treatment options are in high demand, especially at community health centers with limited staff and resources. We have developed an online telehealth-based, 16-week group psychotherapeutic intervention program called Program for Alleviating and Resolving Trauma and Stress (PARTS) based on the Internal Family Systems psychotherapy framework. The goal of this study is to test the feasibility, acceptability, and preliminary efficacy of PARTS through a randomized controlled trial.

METHOD: This randomized controlled trial randomized patients with PTSD (N = 60) to PARTS (n = 30) or a well-matched active control condition called Nature-Based Stress Reduction for Trauma Survivors, with each arm receiving 16 weekly group sessions and eight biweekly individual counseling sessions. The two arms were compared on intervention adherence, treatment satisfaction, and PTSD symptom changes as measured by the Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, fifth edition.

RESULTS: Overall, patients in the PARTS arm attended more group sessions compared to the control arm and reported higher levels of group satisfaction (p < .05). Both treatment arms showed statistically significant reduction of Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, fifth edition scores (p < .001) without significant differences between the two treatment arms.

CONCLUSIONS: This study demonstrated the feasibility and acceptability of PARTS as a group-based PTSD treatment. (PsycInfo Database Record (c) 2026 APA, all rights reserved).