Tag: nevin manimala

JAMA Netw Open. 2025 Nov 3;8(11):e2543156. doi: 10.1001/jamanetworkopen.2025.43156.

ABSTRACT

IMPORTANCE: In the US, 1 in 5 adult suicide decedents has spent at least 1 night in jail in the year prior to death.

OBJECTIVE: To evaluate the effectiveness of the Safety Planning Intervention (SPI) with telephone follow-up as an adjunct to enhanced standard care (ESC) compared with ESC alone for reducing suicide events in the 12 months following release from pretrial jail detention.

DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial included individuals with past 30-day suicide risk (suicide ideation with intent and/or suicide attempt) in pretrial jail detention who were recruited from 2 jails from May 11, 2016, to November 13, 2018, with a 12-month follow-up after release. Data analysis was completed from April 2023 to May 2025.

INTERVENTIONS: All participants received ESC. The SPI included a safety planning session in jail followed by 4 to 8 telephone calls 6 months after jail release.

MAIN OUTCOMES AND MEASURES: The primary outcome was the number of suicide events (a composite of suicide attempts and behaviors, suicide-related hospitalizations, and suicide deaths). Secondary outcomes included the number of suicide attempts, weeks and severity of active suicidal ideation, time to first suicide event, psychiatric symptoms, functioning, and hypothesized mediators. Suicidal ideation and behaviors were assessed using the Columbia-Suicide Severity Rating Scale, the Longitudinal Interval Follow-Up Evaluation, and record reviews from area hospitals. Deaths were identified through hospital, state, and national death records. Hospitalizations were measured with the Treatment History Interview and hospital records.

RESULTS: Of 800 participants randomized in jail, 655 (mean [SD] age, 33.0 [10.4] years; 473 males [72%]) were released to the community and included in analyses. Of those, 593 (91%) completed at least 1 follow-up interview. Medical records were available for all 655 participants (100%). Per person-year of follow-up over 12 months, those in the SPI group compared with those in the ESC group had 42% fewer suicide events (mean [SE], 1.82 [0.18] vs 3.11 [0.32]; mean [SE] difference, -1.30 [0.37]; P < .001), 55% fewer suicide attempts (mean [SE], 1.06 [0.14] vs 2.35 [0.33]; mean [SE] difference, -1.33 [0.38]; P < .001). Differences in weeks of suicidal ideation were not statistically significant (mean [SE], 10.39 [0.78] vs 12.86 [1.02]; mean [SE] difference, -2.47 [1.28]; P = .06). There were no other observed differences in outcomes.

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of the SPI compared with ESC, those in the SPI group experienced reduced suicide risk by 42% in the year after jail release. These results suggest that SPI is effective for reducing suicide risk during this high-risk period.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02759172.

PMID:41212557 | DOI:10.1001/jamanetworkopen.2025.43156

JAMA Intern Med. 2025 Nov 10. doi: 10.1001/jamainternmed.2025.5792. Online ahead of print.

NO ABSTRACT

PMID:41212549 | DOI:10.1001/jamainternmed.2025.5792

JAMA Neurol. 2025 Nov 10. doi: 10.1001/jamaneurol.2025.4347. Online ahead of print.

ABSTRACT

IMPORTANCE: Geographic variation in epilepsy incidence among older adults may reflect contextual risk factors and point to opportunities for targeted prevention. However, privacy constraints and sparse case counts have historically limited small-area analyses.

OBJECTIVE: To map incident epilepsy among older adults at the smallest geography permissible by privacy constraints and identify contextual social and environmental determinants associated with high-incidence areas.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study examined Medicare administrative claims from 2016 to 2019 for all counties in the contiguous United States. A random sample of 4 999 999 Medicare Fee-for-Service beneficiaries 65 years or older with non-Hispanic Black and Hispanic beneficiaries oversampled at rates of 1.50 and 1.75 times their representation in the study population. Beneficiaries with incident epilepsy were identified by claims criteria and codes from the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, in 2019 and had no epilepsy claims during the period 2016 to 2018. Data were analyzed from January to March 2025.

EXPOSURES: Area-level social and environmental determinants of health (SEDH), obtained from publicly available sources and linked to beneficiaries’ residences.

MAIN OUTCOMES AND MEASURES: The outcome was area-level epilepsy incidence rate in 2019. To comply with data privacy requirements, the Max-P regionalization method was used to aggregate 3108 counties into 692 “MaxCounties,” each containing at least 11 incident cases. Incidence rates per 100 000 persons were mapped. Associations between SEDH variables and epilepsy incidence were estimated using random forest and multivariable logistic regression.

RESULTS: Among 4 817 147 beneficiaries, 20 263 incident epilepsy cases were identified in 2019 (mean [SD] age, 78.7 [7.5] years; 54.6% women). Incidence rates across MaxCounties varied more than 10-fold (range, 141-1476 per 100 000). In random forest models, higher incidence was associated with insufficient sleep, heat index, physical inactivity, uninsured rate, proportion of non-Hispanic Black residents, and obesity prevalence. In multivariable regression, MaxCounties in the highest tertile for insufficient sleep had nearly double the odds of high epilepsy incidence compared to the lowest tertile (odds ratio [OR], 1.99; 95% CI, 1.10-3.60). Lack of household vehicle access was similarly associated with high incidence (OR, 1.93; 95% CI, 1.16-3.25).

CONCLUSIONS AND RELEVANCE: Our findings highlight the spatial heterogeneity of epilepsy burden in the US Medicare population and underscore the importance of contextual SEDH factors, such as sleep, mobility, and infrastructure, in shaping disease patterns. These insights may help guide targeted public health interventions and resource allocation.

PMID:41212547 | DOI:10.1001/jamaneurol.2025.4347

Eur J Pain. 2025 Nov;29(10):e70166. doi: 10.1002/ejp.70166.

ABSTRACT

BACKGROUND: Hypnosis (H) and virtual reality (VR) are effective behavioural interventions to influence acute pain perception. Hypnotic suggestions have also been shown to modulate the nociceptive flexion reflex (NFR), suggesting the activation of descending modulatory mechanisms affecting spinal nociceptive activity. The combination of these techniques, virtual reality hypnosis (VRH), may reduce pain, but research on their comparative efficacy and mechanisms requires further experimental investigation. This study compared the effects of relaxation hypnosis, VR and VRH on pain perception and nociceptive physiological responses.

METHODS: Twenty-four healthy participants were tested at baseline followed by three experimental conditions (relaxation hypnosis, VR, VRH) in a counterbalanced order. Pain intensity and unpleasantness, as well as NFR amplitude evoked by noxious transcutaneous electrical stimulation, were measured. Bayesian statistics assessed evidence for analgesic effects on each variable.

RESULTS: The strength of evidence in favour of our hypotheses was categorised as follow: BF = 1-3: anecdotal evidence; BF = 3-10: moderate evidence and BF > 10: strong evidence. For NFR values, Bayesian paired-sample T-tests provided anecdotal support for the efficacy of relaxation hypnosis (BF + 0 = 2.11) and stronger evidence for VR (BF + 0 = 10.94) and VRH (BF + 0 = 14). For pain intensity, moderate evidence supported reductions with relaxation hypnosis (BF + 0 = 9.18), while strong evidence was found for VR (BF + 0 = 27.99) and low to moderate for VRH (BF + 0 = 5.88). Similarly, unpleasantness showed anecdotal reduction with hypnosis (BF + 0 = 1.9), and moderate evidence supported VR (BF + 0 = 4.86) and VRH (BF + 0 = 7.18). Across all measures, no significant differences were found between hypnosis, VR and VRH.

CONCLUSION: These findings suggest that these techniques did not differentially affect NFR, pain intensity, or unpleasantness.

SIGNIFICANCE STATEMENT: The strength of this fundamental study is to directly compare hypnosis, VR, and VRH on both pain perception and physiological responses. It shows that VR alone is effective, while adding hypnosis does not always lead to better results and the combination could even create interference in some cases. This article helps to nuance the existing literature and common assumptions about the tool’s use. These findings help clarify how VRH works and to propose guidance for clinical practices and further VRH development.

PMID:41212540 | DOI:10.1002/ejp.70166

Gerontologist. 2025 Nov 10:gnaf243. doi: 10.1093/geront/gnaf243. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: To assess the efficacy of a local volunteer program, delirium optimization with volunteer engagement (DOVE), in preventing in-hospital delirium.

RESEARCH DESIGN AND METHODS: Between February 2023 and June 2024, volunteers provided structured interventions to patients at risk for delirium, as identified by the Delirium Risk Assessment (DRA) score. Interventions are humanities-based and included sensory aide assistance, completion of “get to know me” forms, and conversation. Data were retrospectively acquired from electronic health records and compared to a control cohort, from another medical unit. Delirium occurrence was captured when nursing confusion assessment method (CAM) documentation was positive, or clinician documented delirium diagnoses. Cohorts were matched 1:2 (DOVE vs Control) by age, gender, DRA score, month/year of admission, and length of hospital stay.

RESULTS: A total of 168 patients received interventions by DOVE volunteers, of which 139 of those were matched with 261 controls. In-hospital delirium occurrence was lower in the DOVE cohort compared to the control cohort (46.8% vs 56.7%; P = 0.015). Conditional logistic regressions demonstrated a lower Odds Ratio for delirium occurrence 0.55 (95% Confidence Interval [CI]; 0.34-0.89; P = 0.015) associated with DOVE intervention. Subgroup analyses of delirium occurrence among patients with DRA score of 3-4 demonstrated an OR of 0.56 (95% CI; 0.31-1.01; P = 0.053) between the DOVE and control cohorts.

DISCUSSION AND IMPLICATIONS: In-hospital delirium occurrence was ∼10% lower among DOVE cohort patients. This humanities-based intervention offers a feasible strategy, particularly during times of staffing shortages, and should be considered for broader implementation across healthcare institutions.

PMID:41212537 | DOI:10.1093/geront/gnaf243

Acta Neurol Belg. 2025 Nov 10. doi: 10.1007/s13760-025-02945-2. Online ahead of print.

ABSTRACT

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a rare and aggressive form of extranodal non-Hodgkin lymphoma, most often a diffuse large B-cell lymphoma. Rituximab, an anti-CD20 monoclonal antibody is widely used in PCNSL treatment but its efficacy remains uncertain. Therefore, we conducted a systematic review and meta-analysis to assess the efficacy of rituximab in newly diagnosed adult PCNSL patients.

METHODS: Medline/PubMed and Scopus were searched for studies comparing rituximab/rituximab-containing regimens with therapies not including rituximab in adult PCNSL patients. A random-effects meta-analysis was conducted, and risk ratios (RR) and hazard ratios (HR) were reported with 95% confidence interval (CI). Outcomes included 3- and 5-year overall survival (OS), OS independent of time, 3- and 5-year progression-free survival (PFS), and complete response (CR).

RESULTS: Sixteen studies (three RCTs, thirteen retrospective) with 2,325 patients (rituximab: 1010; control: 1315) were included. Rituximab-containing therapy was significantly associated with higher 3-year OS (RR: 1.37; 95% CI: 1.07-1.76), higher CR rate (RR: 1.37; 95% CI: 1.05-1.79) and reduced hazard of death (HR: 0.65; 95% CI: 0.43-0.98). 3-year PFS showed a non-significant trend favoring rituximab (RR: 1.29; 95% CI: 0.99-1.68) which reached statistical significance in sensitivity analysis after excluding one study (RR: 1.40; 95% CI: 1.12-1.77). No statistically significant differences were observed for 5-year OS (RR: 1.33; 95% CI: 0.99-1.78) or 5-year PFS (RR: 1.24; 95% CI: 0.79-1.94) between the two groups.

CONCLUSION: Our findings indicate that rituximab-containing therapy was associated with improved short-term outcomes in newly diagnosed adult PCNSL. However, long-term advantages remain uncertain. Therefore, there is a need for larger randomized trials with standardized outcome and toxicity reporting and extended follow-up to confirm long-term survival benefit.

PMID:41212511 | DOI:10.1007/s13760-025-02945-2

Clin Pharmacokinet. 2025 Nov 10. doi: 10.1007/s40262-025-01563-8. Online ahead of print.

ABSTRACT

BACKGROUND: Baricitinib is approved for the treatment of adults with moderate-to-severe atopic dermatitis (AD) who are candidates for systemic therapy and has received regulatory authorization in Europe for moderate-to-severe AD in patients 2 to <18 years.

OBJECTIVE: This study aims to optimize dosing for baricitinib in pediatric patients with atopic dermatitis using pharmacokinetic/pharmacodynamic modeling leveraging adult data.

METHODS: The phase III, randomized, double-blind, placebo-controlled study, BREEZE-AD-PEDS (NCT03952559, registration date: 2019-05-16), enrolled patients (aged 2 to <18 years) with moderate-to-severe AD. During a pharmacokinetic (PK) lead-in period, baricitinib concentration data from age-based dose cohorts (4 mg once daily [QD]: 10 to <18 years; 2 mg QD: 2 to <10 years) were compared with actual and simulated concentration values from adult patients receiving baricitinib 4 mg QD. A population PK model incorporating allometric scaling was developed to determine weight-based dosing in pediatric patients that matches adult exposures. The exposure-response (E-R) relationships were analyzed for the primary endpoint: a validated Investigator Global Assessment^® (vIGA-AD) score of 0 or 1 (clear to almost clear skin) with ≥2-point improvement from baseline at week 16. Baricitinib pharmacokinetics were characterized from 393 pediatric patients using a 2-compartment model with allometric scaling on clearance and volume of distribution.

RESULTS: The age-based and subsequent weight-based dosing (2 mg for patients 10 to <30 kg and 4 mg for patients ≥30 kg) was comparable to the 4-mg adult exposure. A clear E-R relationship was observed for the primary endpoint when sorted for age or weight groups.

CONCLUSION: The population PK model developed using baricitinib concentrations from adult patients, with allometric scaling for weight on clearance and volume, adequately predicted exposures in the pediatric population. The PK modeling, with E-R analysis, informed an appropriate weight-based dosing regimen.

PMID:41212510 | DOI:10.1007/s40262-025-01563-8

Int J Hematol. 2025 Nov 10. doi: 10.1007/s12185-025-04095-w. Online ahead of print.

ABSTRACT

This phase 2 study (NCT05105841) evaluated the safety and efficacy of a fixed-duration 12-cycle regimen of venetoclax plus obinutuzumab in Japanese patients with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The primary efficacy endpoint was the complete remission (CR)/complete remission with incomplete marrow recovery (CRi) rate, assessed by an independent review committee (IRC) according to the 2008 International Workshop on CLL criteria. Ten patients (6 male, 4 female; 9 CLL, 1 SLL) with a median age of 69.5 years (range 52-76) received venetoclax for a median duration of 11.3 months (range 9.2-12.4). The IRC-assessed CR/CRi rate based on the best overall response was 90.0% (95% confidence interval 55.5%, 99.7%). All patients experienced at least one treatment-emergent adverse event (TEAE), and three patients (30.0%) experienced at least one serious TEAE. The most common TEAEs included infusion-related reactions (60.0%), decreased neutrophil count (50.0%), and nausea (40.0%). Nine patients (90.0%) experienced TEAEs related to venetoclax, while all ten patients (100.0%) had TEAEs related to obinutuzumab. One patient (10.0%) developed COVID-19 pneumonia, necessitating the discontinuation of venetoclax. These findings demonstrate the high efficacy and manageable safety profile of venetoclax plus obinutuzumab in this patient population.

PMID:41212498 | DOI:10.1007/s12185-025-04095-w

Target Oncol. 2025 Nov 10. doi: 10.1007/s11523-025-01177-x. Online ahead of print.

ABSTRACT

BACKGROUND: Adavosertib is a highly selective, small molecule Wee1 inhibitor that sensitizes tumor cells to cytotoxic agents.

OBJECTIVE: We report results from the lead-in cohorts of two phase II studies: carboplatin/pemetrexed plus adavosertib versus carboplatin/pemetrexed in first-line metastatic non-squamous non-small-cell lung cancer (NSCLC) (NCT02087241); and docetaxel plus adavosertib versus docetaxel in recurrent NSCLC (NCT02087176).

PATIENTS AND METHODS: Both lead-in cohorts assessed early safety and efficacy (objective response rate [ORR]). First-line metastatic treatment was carboplatin (area under the curve to 6 h [AUC₆]) plus pemetrexed 500 mg/m² intravenously on day 1, every 21 days; recurrent treatment was docetaxel 75 mg/m² intravenously on day 1 plus prophylactic granulocyte-colony stimulating factor 6 mg subcutaneously on day 4 every 21 days. All patients received adavosertib 225 mg twice daily orally on days 1-3 (five doses). After a planned safety analysis of the first-line trial, dose and schedule were modified to reduce toxicity.

RESULTS: First-line: 14 patients were enrolled in four treatment cohorts. Median time on trial was 17.3 weeks, with an ORR of 29%. The most common adverse events were diarrhea (50%), nausea (50%), vomiting (50%), anemia (43%), neutropenia (43%), decreased appetite (43%), and dehydration (43%). Recurrent: 32 patients were enrolled. The ORR was 9%. The most common adverse events were diarrhea (66%), anemia (50%), nausea (47%), fatigue (47%), vomiting (44%), and thrombocytopenia (41%).

CONCLUSIONS: Both studies terminated early; the recurrent study after an interim analysis showed increased toxicity and limited efficacy, and the first-line study after a change in first-line standard of care.

TRIAL REGISTRATIONS: ClinicalTrials.gov, NCT02087241 and NCT02087176.

PMID:41212474 | DOI:10.1007/s11523-025-01177-x

Obes Surg. 2025 Nov 10. doi: 10.1007/s11695-025-08368-5. Online ahead of print.

ABSTRACT

INTRODUCTION: Given the global increase in obesity prevalence, there has been an emergence of a multitude of treatment options, specifically less invasive operations, like intragastric balloons, and pharmaceutical treatments like semaglutide. The aim of this study is to evaluate the synergistic effects of the intragastric balloon and semaglutide on weight reduction and weight regain.

METHODS: In this prospective, randomized cohort, adults between the ages of 18 and 65, with a BMI of at least 27 kg/m², were assigned to one of two treatment groups: IGB only or IGB + semaglutide. Subcutaneous injections of semaglutide were administered with increasing dosages on a weekly basis in the second month and were continued after the removal of the intragastric balloon. All participants were monitored, and results were recorded at 3, 6, and 12 months.

RESULTS: Forty patients completed the study (n = 20 per group). The IGB + semaglutide group lost more weight than the IGB only group at 3, 6, and 12 months, with statistically significant differences at 6 months (29.09 ± 3.45 kg vs. 18.35 ± 2.80 kg, p < 0.001) and 12 months (33.03 ± 3.55 kg vs. 15.56 ± 2.50 kg, p < 0.001). After intragastric balloon removal at 6 months, the IGB only group regained previously lost weight while the IGB + semaglutide group continued to lose weight (2.79 ± 1.74 vs. -3.94 ± 2.16, p < 0.001).

CONCLUSION: Adjunctive semaglutide therapy with intragastric balloon (IGB) optimizes weight loss, while enhancing the sustainability achieved with intragastric ballooning alone. This combined therapeutic approach may provide an additional non-invasive intervention that provides optimal results and long-term weight loss maintenance.

PMID:41212463 | DOI:10.1007/s11695-025-08368-5