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PubMed2026

Radiographic assessment and orthodontic intervention effects on orthodontically induced root resorption: a systematic review and meta-analysis of clinical trials.

The relative contribution of radiographic methods and characteristics of the orthodontic intervention to orthodontically induced root resorption (OIRR) remains unknown. The aims of this systematic review and meta-analysis were to (1) estimate the pooled OIRR effect across orthodontic intervention versus comparator contrasts, (2) compare pooled estimates by radiographic method (2D [two-dimensional] vs. 3D/CBCT [three-dimensional/cone-beam computed tomography]), and (3) explore whether force mechanics (intrusive versus nonintrusive) modified OIRR magnitude. Seven randomized controlled trials and one prospective study (January 2010-October 2025) were included. Only OIRR was the outcome, reported as correlation coefficients (r). The primary analysis combined within-study intervention-versus-comparator estimates. Subgroup analysis of 2D versus 3D/CBCT imaging was prespecified, whereas post-hoc analysis of intrusive versus nonintrusive mechanics was performed. The pooled analysis for the primary outcome showed a small, nonsignificant OIRR effect (r = 0.07; 95% confidence interval [CI]: -0.12 to 0.27; p = 0.372) with high heterogeneity (I2 = 84.0%). Radiographic method did not change the pooled estimates significantly (p = 0.331). Force-mechanics analysis showed that intrusive mechanics was related to significantly higher root resorption than nonintrusive mechanics (r = 0.40; 95% CI = 0.15 to 0.65 versus r = -0.03; 95% CI = -0.16 to 0.10; p < 0.001). This accounted for 87.1% of the between-study variance. The average orthodontic intervention effect on OIRR was small and not significant; however, the OIRR magnitude was strongly affected by force mechanics, particularly by intrusive forces. There was no significant difference in pooled estimates by radiographic method; however, 3D/CBCT provides superior volumetric quantification and should be used judiciously according ALARA (as low as reasonably achievable) principles.

Root Resorption↗

PubMed2026

Effect of semaglutide on kidney outcomes in the SELECT, FLOW, and SOUL trials: a prespecified pooled analysis.

BACKGROUND: The GLP-1 receptor agonist semaglutide reduces clinically important kidney outcomes in people with type 2 diabetes and chronic kidney disease (CKD). We aimed to assess the pooled effects of semaglutide on kidney outcomes in prespecified analyses of participant-level data from the diverse populations of the SELECT, FLOW, and SOUL randomised placebo-controlled trials. METHODS: Participants with CKD (FLOW) or atherosclerotic cardiovascular disease (SELECT and SOUL) were randomly assigned semaglutide (once-weekly subcutaneous 1·0 mg [FLOW], once-weekly subcutaneous 2·4 mg [SELECT], or once-daily oral 14 mg [SOUL]) or matching placebo, added to standard of care. The primary outcome in this pooled analysis was time to first occurrence of a kidney composite, defined as onset of persistent 50% or greater reduction in estimated glomerular filtration rate (eGFR), kidney failure (persistent eGFR <15 mL/min per 1·73 m2, or initiation of kidney replacement therapy), kidney-related death, or cardiovascular-related death. Safety was also assessed. FINDINGS: The pooled participants from the trials (N=30 787) had a mean follow-up of 39·5-47·5 months. Among participants assigned to semaglutide, 973 first events of the primary kidney composite occurred compared with 1134 first events for placebo (hazard ratio [HR] 0·84 [95% CI 0·77-0·91]). First events of a narrower secondary kidney composite (excluding cardiovascular-related death from the primary outcome) were also reduced with semaglutide versus placebo (347 and 416, respectively; 0·80 [0·69-0·92]). Safety outcomes were overall similar between groups, and in line with other GLP-1 receptor agonist trials. Serious adverse events were numberically lower with semaglutide than with placebo. INTERPRETATION: Data pooled from three large phase 3 trials suggest that semaglutide reduces the risk of major kidney outcomes in a broad population with cardio-kidney-metabolic disease while having a favourable risk-benefit profile. In people with cardio-kidney-metabolic disease, with and without diabetes, semaglutide (oral or injected) prevents kidney-related and cardiovascular complications and induces adverse events in line with GLP-1 receptor agonist studies, regardless of baseline characteristics within the cardio-kidney-metabolic spectrum. This was a participant-level analysis conducted in a large database of three randomised controlled trials of similar design and examining the same treatment, but there were some differences in participants' baseline characteristics, and in the dose and route of administration of treatment. This pooled analysis adds evidence for the benefit of GLP-1 receptor agonists in general, and semaglutide in particular, in a broad population of people with cardio-kidney-metabolic disease, suggesting that the benefit of semaglutide might not be explained only by its glycaemic effects, weight-management effects, or both. FUNDING: Novo Nordisk.

Humans↗

PubMed2026

A systematic literature review on low-grade myofibroblastic sarcoma of the trunk.

BACKGROUND: Low-grade myofibroblastic sarcoma (LGMS) is a rare malignant mesenchymal tumor, with primary trunk involvement being particularly uncommon. Due to its rarity, associated diagnostic challenges, and variability in management, a comprehensive evaluation of the available evidence is required. This study aims to systematically review the clinical characteristics, treatment strategies, and outcomes of truncal LGMS. METHODS: A systematic literature search was conducted using PubMed, Web of Science, and Embase for articles published from January 1998 to January 2026. The review included full-text articles involving patients with a pathologically confirmed diagnosis of truncal LGMS. The collected data included patient demographics, tumor features, treatment modalities, recurrence, and follow-up status. RESULTS: Of the 404 studies initially identified, 30 studies involving 59 patients with pathologically confirmed truncal LGMS met the inclusion criteria. Outcome analyses of therapeutic management and clinical course included 45 patients with complete follow-up data, including 42 surgically treated patients and 3 non-surgically managed patients. The final evidence base consisted solely of retrospective studies and case reports. No prospective studies or randomized controlled trials were identified. Consequently, a descriptive statistical analysis was conducted instead of a meta-analysis. CONCLUSION: Current evidence indicates that wide excision with negative margins may be a reasonable primary treatment option for truncal LGMS, with case-based reports showing numerically lower recurrence after wide excision, although the evidence is limited and potentially confounded by multiple factors. Radiotherapy or chemotherapy may be considered only on a highly individualized basis for selected unresectable, recurrent, metastatic, anatomically constrained, or margin-positive cases. Given the very limited sample size and heterogeneous treatment indications across published cases, treatment efficacy cannot be reliably estimated from the available data. Prolonged long-term regular follow-up is recommended for all patients, considering the risk of late recurrence.

Humans↗

PubMed2026

Effect of cognitive enhancement therapy for early course schizophrenia on gray matter volume: A confirmatory multisite randomized clinical trial.

BACKGROUND: Cognitive Enhancement Therapy (CET) is an evidence-based cognitive remediation intervention for early course schizophrenia with established benefits for cognition. CET may protect against broad temporolimbic gray matter volume loss associated with cognitive improvement, but this finding has yet to be replicated. This research reexamined if CET protects against temporolimbic gray matter volume loss in an independent and larger multisite early course sample, and if this neuroprotective effect predicts cognitive and social adjustment improvement. METHODS: Ninety-nine participants with early course schizophrenia completed MRI, cognitive, and social adjustment assessments at baseline, 9 (mid-treatment), and 18 (end of treatment) months. Linear mixed-effects models examined the differential impact of CET (n = 56) compared to Enriched Supportive Therapy (n = 43) on temporolimbic gray matter volume in regions-of-interest (ROIs) that previously demonstrated CET-related neuroprotection (primary ROIs), as well as frontotemporal ROIs outlined in the first trial (secondary ROIs). RESULTS: The right rostral anterior cingulate was the only primary ROI to demonstrate a significant group × time interaction, but was unrelated to cognitive and social adjustment change. No secondary ROIs exhibited a differential treatment effect. CONCLUSION: This confirmatory trial did not recapitulate the observed broad pattern of CET-related temporolimbic gray matter volume neuroprotection. Consistent with the larger literature demonstrating limited evidence of cognitive remediation effects on the brain in schizophrenia, these findings underscore the need for continued investigation of CET-related changes with other neuroimaging modalities, especially given its established cognitive benefits. Such information is critical for cognitive remediation optimization based on validated therapeutic mechanisms.

Humans↗

PubMed2026

Prioritizing Parkinson's disease risk-associated mitochondrial candidate genes via multi-omics integrative analysis.

BACKGROUND: Mitochondrial dysfunction has been implicated in Parkinson's disease (PD), but the genetically regulated mitochondrial genes associated with PD risk remain incompletely defined. METHODS: We conducted a summary-data-based genetic epidemiology study integrating summary-based Mendelian randomization (SMR), Heterogeneity in dependent instruments (HEIDI) filtering, and Bayesian colocalization to prioritize mitochondrial-related molecular features associated with PD risk. Mitochondrial-related genes were defined using MitoCarta3.0. Genetically predicted gene expression and plasma protein abundance were evaluated using expression quantitative trait loci (eQTL) data from eQTLGen and GTEx v8, and protein quantitative trait loci (pQTL) data was assessed using International Parkinson's Disease Genomics Consortium (IPDGC) as the discovery genome-wide association study (GWAS) and FinnGen as the replication dataset. Prespecified QTL analyses were interpreted using FDR correction, HEIDI filtering, and colocalization support. DNA methylation QTL analysis, mitochondrial phenotype MR, and single-nucleus RNA-seq analysis were performed as complementary analyses. RESULTS: In the primary eQTL analysis, higher genetically predicted TTC19 expression was associated with lower PD risk (OR = 0.80, 95% CI: 0.74-0.87, PPH4 = 0.80), whereas higher MALSU1 expression was associated with increased PD risk (OR = 2.21, 95% CI: 1.59-3.06, PPH4 = 0.96). Both associations survived FDR correction, passed HEIDI filtering, and showed colocalization support. GTEx whole-blood data supported the direction of the TTC19 association. No mitochondrial protein reached significance after FDR correction and colocalization filtering in the primary pQTL analysis. Complementary methylation analysis highlighted cg06270993 as an exploratory regulatory signal for MALSU1. CONCLUSIONS: This MR-colocalization study prioritizes TTC19 and MALSU1 as genetically supported mitochondrial-related candidate genes associated with PD risk. Further validation is required to define their functional roles in PD pathogenesis.

Humans↗

PubMed2026

Glucocorticoid receptor antagonism in major depressive disorder with childhood trauma: a randomized controlled trial.

Childhood trauma (CT) is a key risk factor for major depressive disorder (MDD) onset and persistence. Hypothalamic-pituitary-adrenal (HPA) axis dysregulation may underlie this link, and preclinical studies suggest glucocorticoid receptor (GR) antagonism can reverse early life stress effects. This study tested whether the GR antagonist mifepristone reduces depressive symptoms in adults with MDD and CT. The RESET-medication study was a randomized, double-blind, placebo-controlled trial evaluating a 7-day course of mifepristone (1200 mg/day) or placebo in 158 adults with MDD and CT, assessed at baseline, 1 week, 6 weeks (primary endpoint), 3 months, and 6 months. The primary outcome was depressive symptom severity (IDS-SR) at week 6; secondary outcomes included symptom severity at other timepoints, clinical response, remission, anxiety, sleep, stress, disability, and salivary cortisol. At week 6, depressive symptoms declined in both groups, with no significant difference between mifepristone and placebo (b=-0.25, d=-0.03, 95% CI [-0.42, 0.36], pnom=0.887), and no group differences were found for secondary outcomes. Morning and evening cortisol were significantly higher with mifepristone at week 1, consistent with GR antagonism, but not at week 6. Adverse events were more frequent with mifepristone; mild and severe events occurred significantly more often, while the proportion reporting at least one adverse event was numerically higher but not statistically significant (93.6%vs. 82.5%, χ²(1)=3.60, p=0.058). Mifepristone produced the expected endocrine response but did not lead to clinical improvements in individuals with MDD and CT compared to placebo.

Humans↗

PubMed2026

[Tafluprost/timolol fixed-dose combination versus tafluprost monotherapy for open-angle glaucoma and ocular hypertension: a multicenter, randomized, double-blind, parallel-group trial].

Objective: To evaluate the efficacy and safety of a preservative-free tafluprost/timolol maleate fixed-dose combination compared with preservative-free tafluprost monotherapy in Chinese patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). Methods: This was a multicenter, randomized, double-blind, parallel-controlled clinical trial conducted across 25 centers, including the Eye & ENT Hospital of Fudan University, from January 2019 to November 2022. Patients diagnosed with OAG or OHT who required enhanced intraocular pressure (IOP) reduction after a 4-week washout period were enrolled. Participants were randomized 1∶1 to receive either tafluprost/timolol or tafluprost once daily for 3 months. The primary endpoint was the change from baseline in mean diurnal IOP (the average of measurements at 8:00, 10:00, and 16:00) at Month 3. Secondary endpoints included IOP changes at individual time points and the proportion of responders achieving predefined IOP reduction thresholds. Safety was assessed via the incidence of adverse events (AEs). Analysis of covariance (ANCOVA) using the Markov Chain Monte Carlo (MCMC) method was employed for the primary endpoint; superiority was established if the upper limit of the 95% confidence interval (CI) was<0 mmHg (1 mmHg=0.133 kPa). Continuous variables in secondary endpoints were compared using ANCOVA, and responder rates were analyzed using Fisher's exact test. Results: A total of 219 patients were enrolled (tafluprost/timolol group: n=110; tafluprost group: n=109). The primary efficacy analysis set included 215 patients (tafluprost/timolol: n=107; tafluprost: n=108). Baseline characteristics were well-balanced between the two groups. The majority of patients were male [127 (59.1%)] with a mean age of (44.80±15.71) years at screening. At Month 3, the mean diurnal IOP reduction from baseline was (6.56±3.44) mmHg in the tafluprost/timolol group and (5.36±2.94) mmHg in the tafluprost group. After adjusting for baseline IOP, the between-group difference was -1.312 mmHg (95%CI: -2.010 to -0.696); as the upper limit was<0 mmHg, tafluprost/timolol demonstrated superior IOP-lowering efficacy to tafluprost. Responder rates for IOP reductions of≥15%,≥25%, and≥30% were significantly higher in the tafluprost/timolol group (P=0.016, 0.028, and 0.032, respectively). The incidence of ocular AEs was 20.0% (22/110) in the tafluprost/timolol group and 26.6% (29/109) in the tafluprost group. The most common AE was conjunctival hyperemia, occurring in 2.7% (3/110) and 8.3% (9/109) of the groups, respectively. Conclusion: Compared with preservative-free tafluprost monotherapy, the tafluprost/timolol combination provides significantly greater IOP reduction in patients with OAG and OHT, while maintaining a favorable safety profile.

Humans↗

PubMed2026

Seroefficacy of a 10-valent pneumococcal conjugate vaccine (Pneumosil®) compared with other pneumococcal conjugate vaccines in children.

BACKGROUND: A new 10-valent pneumococcal conjugate vaccine (PCV10SII) was prequalified by WHO in 2019 for children based on non-inferiority of immunogenicity to PCV13 and PCV10GSK. However, the efficacy of PCV10SII against pneumococcal carriage or disease has not been compared with other PCVs. We compared the risk of seroinfection in PCV10SII with PCV10GSK and PCV13-vaccinated infants. METHODS: Data were available for 716 infants from two randomised trials comparing the immunogenicity of PCV10SII with PCV13 and PCV10GSK. Serotype-specific IgG levels were measured from serum samples collected at four weeks after the primary vaccination series and at the time of booster vaccination. We defined seroinfection as any increase in serotype-specific IgG between post-primary vaccination and the booster dose, indicating likely colonisation, subclinical infection, or disease. We compared the relative risk (RR) of seroinfection between PCVs. RESULTS: There was no difference in the risk of seroinfection between PCV10SII and PCV10GSK for the shared serotypes, but PCV10SII showed better protection against 6A and 19A, not included in PCV10GSK. Compared with PCV13, the risk of seroinfection was 65% lower in PCV10SII for serotype 14 (RR = 0.35, 95% CI: 0.22, 0.57), 2.27-fold (95% CI: 1.40, 3.68) and 2.91-fold (95% CI: 1.84, 4.60) higher for 6A and 6B seroinfection, and similar for the remaining serotypes. CONCLUSION: PCV10SII demonstrated comparable seroefficacy as PCV10GSK against colonisation by serotypes common to both and may offer better coverage in countries with high prevalence of 6A and 19A disease. The serotype-specific differences in seroefficacy between PCV10SII and PCV13 should be considered when evaluating cost effectiveness. Funding Gates Foundation (INV-056261_2023).

Humans↗

PubMed2026

Aortoesophageal Fistula: Mending the Lethal Connection-A Systematic Review and Meta-Analysis.

BACKGROUND: Aortoesophageal fistula (AEF) is a rare, life-threatening condition with limited high-quality evidence to guide management. METHODS: We conducted a systematic review and meta-analysis of PubMed and Scopus through December 2025, evaluating survival and complication outcomes according to treatment strategy and morphological severity. Patients were categorized into 5 groups: TEVAR alone, staged TEVAR followed by surgery, primary open or hybrid surgery, TEVAR with esophageal stenting, and supportive/palliative care. Outcomes were pooled as proportions with 95% confidence intervals (CIs). RESULTS: A total of 167 reports representing 528 patients were included. Overall 30-day mortality was 31.2% (95% CI 27.0% to 35.7%) and 1-year mortality 41.2% (95% CI 36.2% to 46.4%). Infection occurred in 32.6%, reintervention in 20.2%, and recurrence in 13.2%. Staged TEVAR followed by surgery showed favorable survival (30-day 12.7%, 1-year 26.1%) but high infection (66.7%) and reintervention (43.2%) rates. TEVAR with esophageal stenting had the lowest early mortality (5.0%) but frequent reintervention (54.5%) and 1-year mortality of 33.3%. TEVAR alone demonstrated the lowest 1-year mortality among definitive strategies (25.5%) but notable recurrence (26.9%). Primary open or hybrid surgery carried higher early and late mortality, while supportive/palliative care had the worst outcomes. Morphological severity correlated strongly with mortality, infection, reintervention, and recurrence, with type IV lesions showing particularly poor prognosis. CONCLUSION: Despite contemporary management, AEF carries high early and late mortality. Definitive strategies, particularly staged TEVAR followed by surgery, offer improved survival but increased complications. Morphology-guided, individualized management is recommended.

Adult↗

PubMed2026

Comparative Effectiveness of Oral Ivermectin, 1% Permethrin Shampoo, and 4% Dimethicone Liquid Gel in Treatment of Pediculosis Capitis among School Children in Chachoengsao Province, Thailand.

Pediculosis capitis remains a persistent public health issue, especially in developing countries where resistance to standard neurotoxic pediculicides like permethrin is increasingly prevalent. This study aimed to compare the effectiveness of alternative treatment options against the standard care in a resource-limited setting. We conducted a single-blind randomized controlled trial involving three primary schools in Chachoengsao Province, Thailand (ClinicalTrials.gov: NCT06332872). Eighty-five female participants ages 6-13 years with active infestations were enrolled. Schools were randomly assigned to three treatment arms: 1) oral ivermectin (200 µg/kg) on Days 0 and 7; 2) 1% permethrin shampoo on Days 0 and 7, or 3) 4% dimethicone liquid gel as a single dose on Day 0. The primary outcome was the cure rate, defined as the absence of live lice and viable nits upon clinical assessment on Day 9. Of the 66 participants included in the final per-protocol analysis, oral ivermectin achieved a cure rate of 95.5% (21/22), which was significantly higher than that of the 1% permethrin standard of care (37.0%; 10/27) and the 4% dimethicone physical suffocant (29.4%; 5/17) (P <0.001). Although dimethicone achieved high initial parasitic clearance on Day 0 (88.2%), a rapid reinfestation rate of 58.8% was observed by Day 9, indicating that a single-dose protocol may be clinically insufficient. Adverse events were mild and temporary across all groups. Oral ivermectin appears significantly more effective than both 1% permethrin and single-dose 4% dimethicone in this population. These findings suggest that permethrin resistance is clinically prevalent and relevant in this area.

Humans↗

PubMed2026

Acetazolamide to prevent ventilatory drive withdrawal in REM sleep apnoea: a randomised controlled trial.

BACKGROUND: Obstructive sleep apnoea (OSA) pathogenesis during rapid-eye movement (REM) sleep has been linked to dips in ventilatory drive and downstream genioglossus hypotonia. The carbonic anhydrase inhibitor acetazolamide is known to increase ventilatory drive and improve OSA severity. Therefore, we tested the effect of acetazolamide on REM-predominant OSA severity (apnoea hypopnoea index (AHI) and hypoxic burden, co-primary outcomes) and underlying physiological mechanisms (ventilatory drive, ventilation and pharyngeal muscle activity). METHODS: 11 participants with REM-predominant OSA per baseline polysomnography (REM AHI/non-REM AHI≥2) were allocated to receiving acetazolamide 500 mg for three nights (first night at half dose) or placebo according to a randomised, crossover, double-blind design. Detailed physiological polysomnography with recording of diaphragm and genioglossus electromyography was conducted after each intervention, with a 1-week washout in between. RESULTS: As hypothesised, acetazolamide reduced AHI by 35.5% (95% CI 23.1% to 46.3%) and hypoxic burden by 35.9% (95% CI 21.1% to 48.4%) vs placebo (p<0.001), meeting the primary endpoint. Mechanistic analysis in REM revealed that, unexpectedly, acetazolamide did not mitigate dips in ventilatory drive versus placebo (first decile (+0.1 (-1.0 to 1.3) L/min, p=0.8). Rather, acetazolamide reduced collapsibility (increased ventilation at eupneic drive: +1.4 (1.2 to 1.8) L/min) and raised muscle responsiveness (ventilation vs drive slope: +32 (25 to 41) %ventilation/drive, p<0.001; genioglossus versus drive slope: +0.33 (0.13 to 0.54) %max/(L/min), p=0.001). CONCLUSIONS: Acetazolamide modestly improved REM OSA, with meaningful improvements in upper airway physiology, but failed to mitigate the dips in ventilatory drive responsible for REM OSA. TRIAL REGISTRATION NUMBER: NCT05589792.

Humans↗

PubMed2026

Antibiotic-impregnated bone graft to prevent infection after total hip arthroplasty (ABOGRAFT): protocol for a randomised, double-blind, placebo-controlled trial.

INTRODUCTION: Studies have shown promising results using bone graft as a carrier for local administration of antibiotics to reduce the risk of prosthetic joint infection (PJI). The objective of this clinical trial is to determine if tobramycin and vancomycin-impregnated bone graft is safe and effective in reducing the rate of PJI after total hip arthroplasty (THA). METHODS AND ANALYSIS: This study is an international, randomised, double-blinded, placebo-controlled clinical drug trial. Patients scheduled for THA (n=1100) requiring bone grafting (excluding revisions due to an ongoing infection) are randomised in a 1:1 ratio to prophylactic treatment with tobramycin and vancomycin or placebo-impregnated bone graft.The primary outcome is the time to reoperation due to infection or diagnosis of PJI, expressed as a relative risk difference between the two groups. A risk reduction of at least 50% is considered clinically relevant. Secondary outcomes are time to and reason for reoperation and implant revision, type of micro-organism and antibiotic susceptibility pattern within 2 and 5 years after surgery. Safety outcomes are the number of adverse events and revision rate due to aseptic loosening. The primary analysis will be performed using proportional hazard models. ETHICS AND DISSEMINATION: The study has been approved under the Clinical Trial Regulation No 536/2014 (EU CT; 2024-510921-25-00). Results will be published in open-access peer-reviewed journals and disseminated to patient organisations and the media, and de-identified individual participant data will be curated and shared on reasonable request in accordance with the Findability, Accessibility, Interoperability and Reuse principles, subject to the laws and regulations governing data protection in each participating country. TRIAL REGISTRATION NUMBER: NCT05169229.

Humans↗

PubMed2026

Comparative effects of pharmacological interventions in the prophylactic treatment of tension-type headache: systematic review and network meta-analysis.

BACKGROUND: Tension-type headache (TTH) is the most common neurological disorder. The comparative effect of pharmacological interventions for TTH prophylaxis remains unclear. We aimed to assess the comparative effects of pharmacological interventions in the prophylactic treatment of TTH. METHODS: Ovid Medline, Embase, and Cochrane were searched from inception to 12 December, 2025. Randomized controlled trials (RCTs) of medications compared to placebo or another medication for preventing TTH were included. The primary outcome was headache days per month. A Bayesian random-effect model was employed as the primary analysis of chronic TTH. RESULTS: Thirty-five RCTs were included, 33 (88.6%) RCTs involved chronic TTH patients, and 24 RCTs provided available data for meta-analysis. Amitriptyline 100 mg presented more reduction of monthly headache days than placebo at 4 and 8 weeks (4 weeks: MD -6.59, 95% CrI -11.22 to -0.64; 8 weeks: MD -6.14, 95% CrI -10.27 to -0.87). BTX-A 100 U can reduce monthly headache days (MD -3.79, 95% CrI -7.16 to -0.33). Amitriptyline 100 mg was the highest-ranked treatment for monthly headache days at 4 (SUCRA 0.85), 8 (SUCRA 0.85), and 24 (SUCRA 0.87) weeks; 12 weeks was lidocaine 25 ml (SUCRA 0.75). Amitriptyline 100 mg and BTX-A 500 U showed a higher adverse event rate than placebo. CONCLUSION: Amitriptyline 100 mg and BTX-A 100 U may be options to reduce monthly headache days in patients with chronic TTH. Given the low to very low certainty of evidence, high risk of bias, and high heterogeneity, more studies are needed. TRIAL REGISTRATION: PROSPERO (CRD42025639586).

Humans↗

PubMed2026

Validation of the newly introduced Deauville score 5a for patients treated for advanced-stage classic Hodgkin lymphoma.

The Lugano Imaging Committee recently refined the Deauville score (DS), subdividing DS5 into DS5a (>2× liver uptake without new lesions) and DS5b (new lesions). We investigated whether this improves prognostic discrimination at interim positron emission tomography (PET) after 2 cycles (PET-2) in patients with advanced-stage classical Hodgkin lymphoma (AS-cHL) treated in recent German Hodgkin Study Group randomized phase 3 trials. The primary analysis cohort was HD18 postamendment standard arms (uniform treatment with 6 cycles of escalated doses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone [eBEACOPP]); sensitivity cohorts were HD18 intention-to-treat and HD21 eBEACOPP and brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone arms. Progression-free survival (PFS) was analyzed by landmark Cox models starting at PET-2. DS5a was infrequent (4%-6% across cohorts; 39/639, 67/1745, 33/568, and 29/560). In the primary cohort, DS5 was associated with inferior PFS vs DS1 to DS3 (hazard ratio [HR], 3.00; 95% confidence interval [CI], 1.25-7.23) and vs DS1 to DS4 (HR, 2.35; 95% CI, 1.01-5.50). Across sensitivity cohorts, DS5a remained adverse compared with DS1 to DS4 (HR range, 2.57-5.47), whereas DS4 according to the new definition did not consistently separate from DS1 to DS3, which is likely a result of PET-adapted treatment. Overall survival trends were concordant, but interpretation is limited by few events. To our knowledge, this is the first prognostic validation of the refined DS in prospectively randomized trial populations. The newly introduced DS5a isolates a small high-risk AS-cHL, which further supports risk assessment and adaptation using quantitative biomarkers from PET. The HD18 and HD21 trials were registered at www.clinicaltrials.gov as NCT00515554 and NCT02661503, respectively.

Humans↗

PubMed2026

Clinical performance of two lithium disilicate CAD/CAM materials in posterior Class II inlay restorations: A 48-month randomised split-mouth clinical trial.

OBJECTIVES: To compare the clinical performance of Amber Mill (AM) and IPS e.max CAD (EM) lithium disilicate computer-aided design/computer-aided manufacturing (CAD/CAM) materials in posterior Class II inlay restorations and characterise their baseline properties. METHODS: Thirty-four adults received paired AM and EM posterior Class II inlays (68 restorations) in a triple-blind randomised split-mouth trial followed for 48 months. Restorations were evaluated at baseline and annually using revised World Dental Federation (FDI) criteria, with fracture and retention as the primary endpoint. Baseline characterisation included flexural strength, shear bond strength, translucency parameter, and scanning electron microscopy. McNemar, Wilcoxon signed-rank, Friedman, one-way analysis of variance, Tukey post hoc, and inter-rater agreement analyses were used. RESULTS: At 48 months, 18 paired participants were available for primary analysis. Failures occurred in 2 of 18 AM restorations and in 3 of 18 EM restorations, corresponding to success rates of 88.9% and 83.3%, respectively, with no significant between-material difference (McNemar p = 1.000). No catastrophic bulk ceramic fracture was observed. Secondary FDI scores remained mostly within the clinically acceptable range; marginal staining deteriorated over time in both groups (p < .001) without significant between-material differences. Baseline material testing showed significant material- and translucency-dependent differences in flexural strength, shear bond strength, and translucency. CONCLUSIONS: Within the limitations of the 48-month follow-up and the tested Class II inlay indication, AM showed clinical performance comparable to EM. Observed clinical complications were related to retention or marginal/interface behaviour. CLINICAL SIGNIFICANCE: For posterior Class II lithium disilicate CAD/CAM inlays, medium-term complications were mainly retention/interface-related, suggesting adhesive-interface durability may be as important as baseline ceramic strength.

Humans↗

PubMed2026

USleep: efficacy of app-based audio interventions to improve sleep disturbance in working adults, a multi-arm randomized controlled trial.

STUDY OBJECTIVES: To evaluate the efficacy of three categories of standalone, audio-based sleep interventions (Bedtime Stories, Sleep Sounds, Sleep Skills) delivered via mental health application (MHapp) in improving sleep among working adults with sleep disturbance. METHODS: A multi-arm, parallel randomized controlled trial was conducted. Adults with self-reported sleep disturbances were recruited online and randomly allocated to Bedtime Stories, Sleep Sounds, Sleep Skills, or digital control. Participants completed self-report questionnaires on sleep disturbance and other related outcomes at baseline (t0) and after the 4-week intervention (t1). The primary analysis followed an intention-to-treat approach using mixed-effects models. RESULTS: A total of 495 working adults (mean age = 32.7 years; 55.8% female) were randomized. For sleep disturbance (primary outcome), the between-group Hedges' g effect sizes were very small and not statistically significant (Bedtimes stories vs. control: g = 0.12, 95% CI -0.13 to 0.37, Sleep Sounds vs. control: g = 0.14, 95% CI -0.11 to 0.39, Sleep Skills 0.07, 95% CI -0.07 to 0.29), with slightly greater reductions in sleep disturbance for the intervention groups than control. The same pattern was observed for sleep-related impairment, mental health, well-being, and pre-sleep arousal. CONCLUSION: Audio-based sleep interventions delivered via a MHapp did not demonstrate superior efficacy over a digital control condition in reducing self-reported sleep disturbance among working adults. Although safe and well-tolerated, their use as standalone treatments for sleep disturbance is not supported by these findings. Future research should explore effectiveness in real-world settings, including user content choice across categories, and use objective sleep measures. CLINICAL TRIAL REGISTRATION: Registered at https://www.isrctn.com/ under "Evaluating the efficacy of audio-based digital tools to improve sleep on the Unmind workplace well-being platform"; https://www.isrctn.com/ISRCTN13426045; registration number: 13426045.

Humans↗

PubMed2026

Clinical Trial: Phase 3 Trial of Resmetirom Versus Placebo in Metabolic Dysfunction-Associated Steatohepatitis-Reanalysis of Fibrosis Stage 2-3 Subset.

BACKGROUND: Resmetirom is an oral thyroid hormone receptor beta agonist clinically used to treat metabolic dysfunction-associated steatohepatitis (MASH) among adults with stage F2 or F3 fibrosis. AIMS: Because the pivotal, 52-week, randomized, controlled, phase 3 MAESTRO-NASH trial (once-daily oral resmetirom 80 or 100 mg or placebo) included patients with F1, F2, or F3 fibrosis, we conducted a post hoc analysis aimed at assessing treatment response in the subset of patients with stages F2 and F3 fibrosis, consistent with the approved label population. METHODS: Co-primary end points were MASH resolution (hepatocellular ballooning score 0, lobular inflammation score ≤ 1, and ≥ 2-point nonalcoholic fatty liver disease activity score [NAS] reduction from baseline) with no fibrosis worsening, and ≥ 1-stage fibrosis improvement with no NAS worsening at Week 52. RESULTS: Among 917 patients with F2 or F3 fibrosis, metabolic risk factor prevalence was high (hypertension, 78.0%; dyslipidemia, 71.1%; type 2 diabetes, 67.0%). MASH resolution was achieved by 25.7% in the 80-mg group, 29.9% in the 100-mg group, and 9.5% in the placebo group (p < 0.0001 for both comparisons with placebo). Respective percentages with fibrosis improvement were 26.5%, 28.9%, and 17.3% (p < 0.01 for both comparisons). From baseline to Week 24, low-density lipoprotein cholesterol decreased by 11.7% and 13.7% in the 80- and 100-mg resmetirom groups, respectively, and increased by 2.3% with placebo (p < 0.0001 for both comparisons). No new safety signals emerged. CONCLUSION: Results among patients with F2 and F3 fibrosis were consistent with the primary MAESTRO-NASH analysis population, demonstrating efficacy and safety of resmetirom after 52 weeks.

Humans↗

PubMed2026

Clinical Performance in Critical Care Simulation under Sleep Deprivation: Effects of Power Napping in the Recovery Napping Protocol for Anesthesiologist Performance (R-NAP) Randomized Controlled Trial.

BACKGROUND: Sleep deprivation is common among anesthesia residents and impairs both technical and nontechnical skills such as leadership. Napping is recommended in fatigue management across healthcare and other safety-sensitive sectors, yet its effectiveness for healthcare providers remains underexplored. This study evaluated whether a 30-min nap opportunity improved simulated crisis performance after a 24-h shift. METHODS: Residents were tested twice: once rested and once using a 24-h shift to induce partial sleep deprivation. Between sessions, they were trained in fatigue management. In the sleep-deprived condition, they were randomized to a nap opportunity or a control condition. Actigraphy objectively assessed sleep and nap duration. The primary endpoint was overall simulated clinical performance (0 to 200; combined technical and nontechnical scores). Secondary endpoints were technical and nontechnical subscales. Group effects were primarily tested using intention-to-treat regression models adjusted for rested performance, previous sleep, and critical care experience. RESULTS: Thirty-five residents were enrolled (nap opportunity, n = 19; control, n = 16). In the primary analysis sample (n = 27), clinical performance was 14.8 points higher after the nap opportunity compared with controls (95% CI, 2.8 to 26.9; P = 0.018), corresponding to a 7.4% improvement. Technical skills did not differ significantly between groups, although more sleep was associated with better technical performance. Nontechnical skills were higher in the nap opportunity condition (+11.0 points; 95% CI, 2.2 to 19.8; P = 0.016), including significant effects of leadership and resource utilization. Exploratory analyses suggested associations between longer nap duration and multiple performance domains, strongest for technical skills ( P = 0.010). CONCLUSIONS: Napping appears to enhance clinical performance, while the nap opportunity, nap duration, and previous sleep deprivation each influenced technical and nontechnical performance in distinct ways. These findings support integrating napping and recovery into medical education and scheduling.

Adult↗