Nevin Manimala

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

Odontology. 2025 Nov 10. doi: 10.1007/s10266-025-01256-5. Online ahead of print.

ABSTRACT

This study evaluated the effects of three chelating agents-glycolic acid (GA), ethylenediaminetetraacetic acid (EDTA), and etidronic acid (HEDP)-combined with different irrigation activation techniques on the pushout bond strength of Biodentine to root dentin after calcium hydroxide removal. A total of 120 extracted single-rooted mandibular premolars were randomly assigned to nine experimental and one control group (n = 12). Following Ca(OH)₂ dressing and incubation, canals were irrigated with GA, EDTA, or HEDP, each activated using passive ultrasonic irrigation (PUI), XP-Endo Finisher (XPF), or conventional needle irrigation (CNI). Biodentine was placed into 2 mm-thick root slices, and pushout bond strength was measured using a universal testing machine. Statistical analysis was performed using one-way ANOVA for group comparisons, and two-way ANOVA was used to evaluate factor effects (α = 0.05). Overall, GA produced higher bond strength than EDTA (p = 0.027). The difference between GA and HEDP was not significant under PUI activation; however, GA yielded significantly higher bond strength than HEDP when activated with CNI or XPF. Using 10% GA with PUI enhanced Biodentine-dentin adhesion, suggesting its potential as a biocompatible and effective alternative to conventional chelators in regenerative endodontic treatments, improving coronal sealing and long-term stability.

PMID:41212455 | DOI:10.1007/s10266-025-01256-5

Jpn J Radiol. 2025 Nov 10. doi: 10.1007/s11604-025-01908-0. Online ahead of print.

ABSTRACT

PURPOSE: Observation of the clearance of gadolinium-based contrast agents (GBCA) in patients with cerebral infarction and Moyamoya disease (MMD) using vessel-wall MRI (VW-MRI).

METHODS: This prospective study included 11 patients with recent cerebrovascular disorder and 6 patients with MMD who were scheduled for VW-MRI. All participants underwent whole brain delay alternating with nutation for tailored excitation-prepared T1-weighted variable flip angle turbo spin echo (DANTE T1-SPACE) imaging before, immediately after, and 1-6 h after gadolinium injection. Additionally, a phantom experiment was conducted to assess the signal intensity according to T1 values using DANTE T1-SPACE and 3D real inversion recovery sequences.

RESULTS: All five large infarction cases (≥ 5 cm) had delayed meningeal enhancement on the ipsilateral side, while none of the remaining six small infarction cases (< 5 cm) exhibited delayed meningeal enhancement on MRI. More than half of the entire cases had delayed white matter enhancement adjacent to the infarction. No MMD cases showed delayed enhancement outside postoperative regions. In the phantom experiment, DANTE T1-SPACE (TR = 700-1300 ms) demonstrated stable signal intensity across a T1 range of approximately 500-1000 ms. This T1 range corresponds to signal intensity ≈ 200-600 typically observed in regions showing delayed enhancement in clinical stroke and MMD cases.

CONCLUSIONS: Delayed meningeal enhancement observed in patients with large cerebral infarctions likely reflects alterations in brain clearance pathways. The absence of such enhancement in MMD supports that these enhancements are not attributable to collateral circulation. Phantom validation confirmed that the imaging parameters used in the DANTE T1-SPACE sequence were sufficient to detect subtle contrast enhancement in the clinically relevant T1 range.

PMID:41212449 | DOI:10.1007/s11604-025-01908-0

Curr Allergy Asthma Rep. 2025 Nov 10;25(1):52. doi: 10.1007/s11882-025-01234-5.

ABSTRACT

PURPOSE OF REVIEW: The optimal management of mucosal tissues during endoscopic sinus surgery (ESS) for chronic rhinosinusitis with nasal polyps (CRSwNP) remains controversial. This systematic review and network meta-analysis aimed to compare the efficacy and safety between mucosa-preserving surgical techniques, such as functional endoscopic sinus surgery (FESS) and extended endoscopic sinus surgery (EESS), and radical mucosa-resecting endoscopic sinus surgery (RESS) for the treatment of CRSwNP.

RECENT FINDINGS: Nine studies involving 1,224 patients were included. RESS was associated with significantly lower recurrence rates compared to both FESS (relative risk [RR]: 2.37; 95% confidence interval [CI]: 1.64, 3.43) and EESS (RR: 2.22; 95% CI: 1.48, 3.36). EESS demonstrated a significantly lower revision surgery rate than FESS (RR: 2.95; 95% CI: 1.89, 4.82). Additionally, RESS showed greater improvement in overall symptom/severity visual analogue scale (VAS, 0-10 cm) scores compared to FESS (mean difference [MD]: -2.82, 95% CI: -3.02, -2.62) and EESS (MD: -2.64, 95% CI: -4.09, -1.21). No significant differences were observed in complication rates among these surgical techniques. Besides, no statistically significant differences were found in VAS-loss of smell score, Sino Nasal Outcome Test-22 score, or Lund-Kennedy endoscopic score. Mucosal resection during endoscopic sinus surgery is associated with reduced postoperative recurrence and improved overall symptom control in patients with CRSwNP compared to mucosal preservation techniques. The safety profiles of these surgical approaches are comparable.

PMID:41212426 | DOI:10.1007/s11882-025-01234-5