Category: Nevin Manimala

JAMA Netw Open. 2026 Apr 1;9(4):e267403. doi: 10.1001/jamanetworkopen.2026.7403.

ABSTRACT

IMPORTANCE: Targeting impaired reward processing that underlies anhedonia and diminished positive affect is essential for reducing key risk factors in depression and anxiety, including suicidality and relapse. However, mechanistic research in this area remains limited.

OBJECTIVES: To assess whether a novel psychosocial intervention engages reward systems more than a mechanistically distinct comparison therapy, and whether alterations in reward and threat processing differentially mediate clinical outcomes.

DESIGN, SETTING, AND PARTICIPANTS: This was an assessor-blinded, parallel-group, multisite, 2-arm randomized clinical superiority trial. Study recruitment was from December 2021 to January 2024, with final assessment in July 2024. Participants were recruited from academic outpatient treatment centers in Los Angeles, California, and Dallas, Texas, and included treatment-seeking adults with severely low positive affect and moderate to severe depression or anxiety that was functionally impairing. Analyses were conducted with intent-to-treat principles.

INTERVENTION: Participants underwent 15 weekly individual therapy sessions of positive affect treatment (PAT) or negative affect treatment (NAT).

MAIN OUTCOMES AND MEASURES: Clinical status was self-reported positive affect (using the Positive and Negative Affect Schedule-Positive subscale), interviewer-rated anhedonia (embedded within the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition), and self-reported depression and anxiety (using the Depression, Anxiety, and Stress Scale). Target measures were 14 self-reported, behavioral, and physiological measures of reward anticipation-motivation, response to reward attainment, reward learning, and threat. Analyses included mixed-effects multilevel models.

RESULTS: In total, 98 participants (mean [SD] age, 32.8 [12.2] years; 65 [66.3%] female) were randomized to receive PAT (n = 51) or NAT (n = 47). Multivariate multilevel model analyses of the 3 clinical status variables as a multivariate outcome showed that clinical status improved more with PAT than NAT (b = -0.06 [95% CI, -0.11 to -0.01]; t3039 = 2.43; P = .02; d = 0.27) and that PAT had better (higher) scores on clinical status than NAT at the 1-month follow-up (b = -0.21 [95% CI, -0.41 to -0.02]; t3039 = 2.11; P = .04; d = 0.21). Improvements in reward anticipation-motivation (b = 0.02 [95% CI, 0.01-0.03]; t1307 = 4.36; P < .001; d = 0.40) and reward attainment (b = 0.04 [95% CI, 0.01-0.06]; t1405 = 3.16; P = .002; d = 0.18) targets were comparable for PAT and NAT. Of 7 reward and threat self-reported target measures, 6 mediated improvements in clinical status, but none of the behavioral or physiological measures did. There was limited evidence for moderated mediation.

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of 98 adults with severely low positive affect, depression, and anxiety, findings suggested that modulation of reward and threat processes was a central mechanism of therapeutic improvement, with a reward-focused intervention producing superior clinical outcomes.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05203861.

PMID:42030048 | DOI:10.1001/jamanetworkopen.2026.7403

JAMA Netw Open. 2026 Apr 1;9(4):e268631. doi: 10.1001/jamanetworkopen.2026.8631.

ABSTRACT

IMPORTANCE: Motor vehicle collisions are a leading cause of death among teenagers. Effective strategies to reduce risky driving, especially for teenage drivers cited for traffic violations, are critical yet underdeveloped.

OBJECTIVE: To evaluate the effectiveness of ProjectDRIVE, an in-vehicle and smartphone-based driving feedback intervention combined with parent communication training, in reducing risky driving events and unsafe driving behaviors among teenagers with traffic violations.

DESIGN, SETTING, AND PARTICIPANTS: This 3-arm, parallel randomized clinical trial enrolled 240 parent-teenager dyads, randomized evenly (80 per arm) to the control arm (device installed without feedback), the driving feedback only arm, or the driving feedback plus parent training arm. Enrollment occurred from September 28, 2020, to June 30, 2024, with 6 months of follow-up. Participants included teenagers aged 16 to 17 years with an intermediate license and a moving violation, and their parent or guardian, enrolled from 6 juvenile traffic courts across Ohio.

INTERVENTIONS: Intervention teenagers received real-time, in-vehicle and smartphone-based feedback, as well as biweekly emailed reports. Parents in the driving feedback plus parent training arm accessed their teenager’s driving reports, completed virtual communication training, and received an online guide for discussing safe driving.

MAIN OUTCOMES AND MEASURES: Intent-to-treat analyses assessed intervention effects on the incidence rate of risky driving events per 1000 miles and the proportion of miles driven involving unsafe driving behaviors, measured using telematics.

RESULTS: Among 240 parent-teenager dyads (teenager mean [SD] age, 16.7 [0.5] years; 123 female teenagers [51.3%]), teenagers completed 160 095 trips. Compared with control, driving feedback plus parent training significantly reduced risky driving event incidence (adjusted incidence rate ratio [AIRR], 0.68; 97.5% CI, 0.51-0.90) and the proportion of miles driven while speeding (adjusted exponentiated β coefficient, 0.54; 97.5% CI, 0.47-0.68). Driving feedback alone did not significantly reduce risky driving but did reduce miles driven while speeding (adjusted exponentiated β coefficient, 0.64; 97.5% CI, 0.54-0.79). Male teenagers exhibited higher rates of risky driving compared with female teenagers, including hard braking (AIRR, 1.39; 95% CI, 1.11-1.73) and sudden acceleration (AIRR, 2.13; 95% CI, 1.42-3.19), as well as greater proportions of miles driven while speeding.

CONCLUSIONS AND RELEVANCE: Combining driving feedback with parent communication training reduced risky driving among teenagers with traffic violations. Continued parental engagement after licensure, especially after traffic violations, might be key to reinforcing driving safety among teenagers.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04317664.

PMID:42030047 | DOI:10.1001/jamanetworkopen.2026.8631

JAMA Netw Open. 2026 Apr 1;9(4):e269261. doi: 10.1001/jamanetworkopen.2026.9261.

ABSTRACT

IMPORTANCE: Systemic glucocorticoids have little or no demonstrated efficacy for acute respiratory infections (ARIs) and have known adverse effects. Clinicians in urgent care centers vary widely in their use of glucocorticoids for patients seen for ARIs.

OBJECTIVE: To develop and test a multifaceted urgent care stewardship program to reduce the use of glucocorticoids for ARIs.

DESIGN, SETTING, AND PARTICIPANTS: This quality improvement study included clinicians seeing patients from January 2023 through April 2025 presenting with ARIs at 2 urgent care centers within an academic health system.

INTERVENTIONS: Beginning in February 2024, clinicians were emailed a survey about steroid stewardship, received brief virtual clinician education, and were provided with educational pamphlets to distribute to patients. In May and December 2024, they received email feedback using peer comparison with descriptive and injunctive norms.

MAIN OUTCOMES AND MEASURES: Segmented Poisson regression with clinician-level random effects was used to analyze monthly clinician-level rates of ARI urgent care visits where a systemic glucocorticoid was prescribed (steroid stewardship-eligible visits) before (January 2023 to January 2024) and after (February 2024 to April 2025) steroid stewardship. Visits were excluded for patients with conditions where glucocorticoid treatment may be clinically appropriate. Retrospective interrupted time series modeling of glucocorticoid prescriptions was performed before and after stewardship program implementation.

RESULTS: From January 2023 to April 2025, 10 808 patients (mean [SD] age, 58 [24] years; 6879 [64%] female; 3929 [36%] male) were seen for ARI by 96 clinicians (78 [81%] females; 18 [19%] male; 32 [33%] advance practice nurses; 38 [40%] physicians; 26 [27%] physician assistants) presenting with ARIs at 2 urgent care centers within an academic health system. Participating clinicians attended 14 530 steroid stewardship-eligible visits (7130 before and 7400 during stewardship). The most common diagnoses were nonspecific upper respiratory infection (17%), acute pharyngitis (15%), and acute bronchitis (7%). The mean (SD) clinician-level observed rate per 100 stewardship-eligible visits of systemic glucocorticoid prescriptions decreased from 20.4 (17.8) in the period before stewardship to 8.8 (14.5) during the stewardship period (P <.001). During the stewardship period, the relative rate of glucocorticoid prescribing decreased by 0.94 (95% CI, 0.92 to 0.96; P <.001) per month compared with the period before stewardship.

CONCLUSIONS AND RELEVANCE: In this quality improvement study of a multi-faceted, behavioral science-informed intervention to promote glucocorticoid stewardship for ARIs in urgent care settings, implementation was associated with reductions in glucocorticoid prescribing.

PMID:42030044 | DOI:10.1001/jamanetworkopen.2026.9261

J Eval Clin Pract. 2026 Apr;32(3):e70431. doi: 10.1111/jep.70431.

ABSTRACT

RATIONALE: Meta-analysis is central to evidence-based medicine, yet the implications of model choice remain poorly understood among clinicians. The distinction between fixed-effect and random-effects models is often treated as a technical detail, although it fundamentally defines the scope of inference.

AIMS AND OBJECTIVES: To provide a conceptually grounded and practically oriented tutorial on how to choose, perform, and interpret fixed-effect and random-effects meta-analyses in clinical research.

METHOD: This tutorial combines conceptual explanations, simulated data and re-analyses of published meta-analyses to illustrate how different modelling frameworks influence pooled estimates, uncertainty intervals and clinical interpretation. Contemporary methodological guidance, including Cochrane recommendations, is integrated throughout.

RESULTS: Fixed-effect models yield conditional inferences restricted to the included studies, often producing narrower confidence intervals by ignoring between-study variability. In contrast, random-effects models account for heterogeneity and provide unconditional inferences that generalise to a broader range of clinical settings, typically resulting in wider intervals. Re-analyses demonstrate that statistically significant findings under fixed-effect models may become non-significant when appropriate random-effects methods are applied, particularly when using robust estimators and Hartung-Knapp-Sidik-Jonkman adjustments. Prediction intervals further illustrate the expected variability of effects across future comparable settings.

CONCLUSION: Model choice in meta-analysis is not a statistical afterthought but a conceptual decision that determines the inferential target. Random-effects models will often be more appropriate when the aim is to inform clinical practice across diverse settings, whereas fixed-effect models are appropriate only under strict assumptions or as sensitivity analyses. Transparent reporting and alignment with contemporary methodological standards are essential to ensure valid and clinically meaningful evidence synthesis.

PMID:42030028 | DOI:10.1111/jep.70431

Support Care Cancer. 2026 Apr 24;34(5):461. doi: 10.1007/s00520-026-10642-w.

ABSTRACT

OBJECTIVE: To evaluate the disproportionality, times to onset, and outcomes of cardiac adverse events (AEs) associated with axitinib, using data from the Japanese Adverse Drug Event Report (JADER) database.

METHODS: We analyzed data for the period from April 2004 to December 2024. Those on cardiac AEs were extracted and the disproportionality of axitinib-associated AEs was assessed by calculating reporting odds ratios (RORs).

RESULTS: Of the 2,988,681 reports with sex and age information, we identified 4788 reports of AEs associated with axitinib, including 508 cardiac AEs. Signals were detected for 16 cardiac AEs after adjustment for sex and age. Fatal outcomes were reported for five of these events with particularly high rates observed for cardiac failure, myocarditis, and immune-mediated myocarditis. Median times to onset indicated that cardiac AEs associated with axitinib occurred 14 to 420 days after administration. Weibull distributions showed that seven AEs (blood pressure increased, myocardial infarction, acute myocardial infarction, blood pressure systolic increased, oedema peripheral, oedema, and generalised oedema) occurred constantly throughout the exposure period (random failure type), and stress cardiomyopathy and immune-mediated myocarditis developed in a dose-dependent manner (wear-out failure-type).

CONCLUSIONS: We focused on cardiac AEs associated with axitinib as post-marketing AEs. Some with fatal outcomes may occur not only early in treatment but also later in the course. Continuous monitoring is essential to ensure timely detection and management of these potentially serious AEs in clinical practice.

PMID:42030026 | DOI:10.1007/s00520-026-10642-w

Saudi Dent J. 2026 Apr 24;38(5):52. doi: 10.1007/s44445-026-00154-y.

ABSTRACT

Root canal treatment aims to eliminate organisms within the canal system through the removal of pulp tissue, infected dentin, and necrotic materials. However, experiencing pain or swelling after root canal operations can be a significant concern. Minimally invasive (MI) techniques, such as the TruNatomy rotary file system, are intended to preserve tooth structure. However, conventional systems, such as ProTaper Gold rotary file system, aim for complete debridement. In this meta-analysis, we aim to assess the efficacy of the TruNatomy and ProTaper Gold in reducing postoperative pain. In November 2025, we conducted a systematic search of PubMed, Scopus, Web of Science, and the Cochrane Library for randomized controlled trials (RCTs) comparing TruNatomy to ProTaper Gold in adult patients with pulpitis. For the meta-analysis, we used R 4.5.0 with R Studio 2024.12.1 + 563. Using a random-effects model, we evaluated dichotomous data using risk ratios (RRs) and 95% confidence intervals (95% CI); whereas continuous data were analyzed using standardized mean difference (SMD) and 95% CI. Visual inspection of the forest plot was used to determine statistical heterogeneity between trials, in addition to I-squared (I2) and chi-squared (Chi2) statistics. Our analysis included four RCTs comprising 381 patients. Pooled analysis showed no statistically significant difference between TruNatomy and ProTaper Gold in pain intensity at 24 h (SMD = 0.03, 95% CI -0.17; 0.23), 48 h (SMD = 0.13, 95% CI -0.16; 0.42), or 72 h (SMD = -0.59, 95% CI -1.33; 0.14). There was no significant difference between the two groups in analgesic intake (RR = 1.2, 95% CI 0.70; 2.06). Also, the presence of postoperative pain at 24 and 48 h was similar in both groups. The results showed low statistical heterogeneity for most outcomes; however, the results should be interpreted with consideration of the clinical variability between the included studies. According to our data, the TruNatomy showed no superiority over ProTaper Gold rotary file systems in managing postoperative pain following root canal therapy. The choice of either approach may be based on other criteria, such as dentin preservation or operator preference. Thus, future large-scale clinical trials should validate these findings.

PMID:42030017 | DOI:10.1007/s44445-026-00154-y

Biomed Res Int. 2026;2026(1):e7129618. doi: 10.1155/bmri/7129618.

ABSTRACT

Worldwide, over 2 billion people lack access to safe drinking water, often relying on unsafe sources that increase hygiene risks and fecal contamination. This study assessed the mediating role of hygienic water handling practices in the relationship between household water security and fecal contamination in Wenago District, Gedeo Zone, South Ethiopia. A community-based cross-sectional survey was conducted between January and April 2024, involving 411 randomly selected households. Data were collected through structured interviews, whereas microbiological analysis of stored water samples was performed using a Wagtech portable testing kit and membrane filtration technique. Statistical analyses were conducted, summarizing descriptive findings in both text and tables. Mediation analysis utilized multiple linear regression models to evaluate the direct and indirect effects. Findings showed that 69.1% of households practiced good water handling, 94.9% faced insecurity, and 93.4% of samples were fecally contaminated. Mediation analysis indicated a significant indirect effect of household water security on contamination through handling practices (B = 13.726; 95% CI: 11.400-16.050; p < 0.001). The direct effect remained significant (B = 28.019, 95% CI: 25.718, 30.321, p < 0.001), confirming partial mediation. These results underscore the importance of hygienic handling in reducing contamination risks and safeguarding public health.

PMID:42030016 | DOI:10.1155/bmri/7129618

Behav Res Methods. 2026 Apr 24;58(5):140. doi: 10.3758/s13428-026-02967-5.

ABSTRACT

Lexique 4, an updated French lexical database, expands upon its predecessor, Lexique 3, by incorporating several significant improvements to enhance its utility in psycholinguistics, computational linguistics, and education. The new version is based on a larger corpus of 316 million words derived from 65,317 documents, including movie, TV show, and documentary subtitles, which offers more accurate frequency estimates and includes contemporary neologisms. Lexique 4 introduces new variables, such as orthographic surface frequency, contextual diversity (CD), and detailed morphological structure, which provide a more comprehensive view of lexical properties. We find that contextual diversity is a slightly better predictor than word frequency, in line with previous work. Moreover, the integration of lexical decision times from the French Lexicon Project into Lexique 4 facilitates more in-depth linguistic research. Enhancements to the user interface, including a redesigned web platform, enable dynamic searches and sorting capabilities, increasing accessibility and usability for researchers. Statistical analyses indicate that the updated frequency measures in Lexique 4 are better predictors of lexical decision times compared to Lexique 3, supporting the value of these enhancements. Overall, Lexique 4 represents a comprehensive and flexible tool for analyzing French lexical properties, making it an essential asset for a broad range of users.

PMID:42030008 | DOI:10.3758/s13428-026-02967-5

Brain Topogr. 2026 Apr 24;39(3):45. doi: 10.1007/s10548-026-01196-5.

ABSTRACT

Entropy rate (ER) and sample entropy (SE) are two metrics that have been used to quantify the syntactic complexity of electroencephalography (EEG) microstate sequences. We here present a theoretical and numerical comparison of these two metrics and apply them to a resting-state EEG dataset from individuals with Alzheimer’s disease (AD) and a control group. We first derive theoretical ER and SE estimates for first-order discrete Markov processes, providing a null hypothesis for statistical testing of higher-order syntax properties. Under the first-order syntax null hypothesis, we find a close mathematical relationship between both metrics that can be expressed by the microstate transition probability matrix. An inequality is derived that shows ER to be an upper bound to SE under the Markov approximation. We quantify accuracy and precision of the theoretical ER and SE estimates on EEG microstate sequences from the healthy control group. We then show that ER and SE identify significant higher-order syntax properties in microstate sequences from the control and AD groups. We investigate continuous and jump microstate sequences. In the former, each time point is labelled with the best matching microstate label, and in the latter, duplicate labels are removed, exclusively retaining transitions between non-identical microstates. Group comparison demonstrates that continuous microstate sequences from the AD group have lower entropy values (ER, SE), whereas jump sequences from the AD group have higher entropy values compared to control. Finally, we introduce a new syntax metric that normalizes ER and SE values with respect to their first-order syntax levels, to assess differences that only depend on syntax order. This metric revealed no differences between control and AD groups for either continuous or jump microstate sequences. This study provides further insights into higher-order microstate syntax and how it can be quantified with respect to the underlying first-order syntax. Similarities and differences between ER and SE as syntax metrics are highlighted and exemplified on experimental data. Our results show that (i) EEG microstate sequences from control and AD subjects show higher-order syntax properties across the tested syntax levels, (ii) continuous and jump sequences from control and AD groups are syntactically different, and (iii) differences between the control and AD groups disappear when higher-order syntax properties are normalized to the group-specific Markov level.

PMID:42030001 | DOI:10.1007/s10548-026-01196-5

Neurocrit Care. 2026 Apr 24. doi: 10.1007/s12028-026-02521-3. Online ahead of print.

ABSTRACT

Traumatic brain injury (TBI) is a major cause of trauma-related mortality. While male individuals are disproportionately affected, the influence of sex on mortality remains controversial, with conflicting evidence suggesting female advantage, disadvantage, or no difference. Clarifying this relationship is crucial for prognosis and sex-specific treatment. A systematic search was conducted on 4 June 2025 in PubMed, Embase, Web of Science, and the Cochrane Library without date restrictions. Observational studies reporting sex-stratified TBI patient mortality with sufficient data to derive effect sizes were included. Screening, full-text assessment, and data extraction were performed independently by multiple reviewers. Random-effects meta-analysis was conducted to calculate odds ratios (OR) for mortality in female versus male individuals, with subgroup and leave-one-out sensitivity analyses as well as meta-regression. Heterogeneity was quantified using I² and prediction intervals. Quality was assessed using an adapted Newcastle-Ottawa Scale. The review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines. A total of 40 studies, encompassing over 1 million patients (383,914 female individuals; 662,748 male individuals), were included. Overall, sex was not significantly associated with TBI mortality [OR 0.99; 95% confidence interval (CI) 0.90-1.09], though substantial between-study heterogeneity and prediction intervals indicated that female mortality could be higher in some contexts and lower in others. Subgroup analyses showed no significant differences by TBI type, age, or severity. Although initial analyses suggested lower female mortality in good-quality studies and higher female mortality in patients with severe TBI and in studies conducted before the 2000s, the findings were not robust in leave-one-out analyses. Meta-regression indicated that mean age differences did not explain heterogeneity between sex and mortality estimates. Concluding, there is no universal biological association between sex and TBI mortality. Instead, the relationship appears context-dependent, varying by study characteristics and patient populations. Future research should move beyond assessing sex as a simplistic risk factor and focus on identifying specific biological and clinical contexts where sex influences outcomes to inform personalized care.

PMID:42029980 | DOI:10.1007/s12028-026-02521-3