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PubMed2026

Single-slice Functional Lung MRI During Metronome-Paced Tachypnea Detects Changes in Regional Ventilation Dynamics After a Single Dose of Dual Bronchodilator Treatment in COPD.

Dual long-acting bronchodilators are a standard treatment in chronic obstructive pulmonary disease (COPD), aimed at alleviating dyspnea, improving exercise tolerance, and preventing exacerbations. Metronome-paced tachypnea (MPT) offers a feasible alternative to exercise testing for the evaluation of dynamic hyperinflation (DH) in COPD. Because MPT can be performed during MRI, its combination with single-slice phase-resolved functional lung (PREFUL) MRI provides a promising approach to investigate changes in regional ventilation dynamics induced by DH. This approach was evaluated in a randomized, investigator-blinded, placebo-controlled, single-dose (SD) crossover trial with a two-week extension of once daily dual bronchodilator medication, in which patients with stable COPD underwent PREFUL MRI during resting tidal breathing (RTB) and during MPT. During RTB, no significant improvements in MRI-derived parameters were observed after SD treatment compared with placebo. During MPT, however, regional ventilation, flow-volume loop correlation, its defect percentage, and end-expiratory lung area improved significantly after SD treatment compared to the placebo scan (all p < 0.02). After multi-dose treatment, five out of six measured parameters improved during MPT, when compared to the baseline scan without bronchodilator treatment (all p < 0.03). In contrast to RTB, PREFUL MRI during MPT was able to detect changes in COPD patients already after SD treatment. The combination of MPT and PREFUL MRI represents a promising method to evaluate the effects of dual bronchodilators on regional ventilation dynamics and hyperinflation.

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PubMed2026

Does impulsivity predict treatment outcomes in PTSD with borderline personality disorder features? Results from a randomized clinical trial.

BACKGROUND: Trauma-focused psychotherapies are first-line treatments for posttraumatic stress disorder (PTSD). However, a substantial proportion of clients do not respond adequately or drop out of therapy prematurely. This has sparked interest in identifying individual-level predictors of treatment outcomes, including improvement in PTSD severity and dropout. Impulsivity may be a predictor because it may interfere with key therapeutic processes, such as cognitive restructuring and emotional processing. Consequently, we present a hypothesis-driven secondary analysis of a 15-month randomized clinical trial comparing Dialectical Behavior Therapy for PTSD (DBT-PTSD) and Cognitive Processing Therapy (CPT) in women with childhood abuse-related PTSD and borderline personality disorder features to test whether impulsivity, assessed at baseline, predicts PTSD improvement and dropout. We further explore whether the dimensions of impulsivity (non-planning, attentional impulsivity, and motor impulsivity) differentially affect the outcomes in DBT-PTSD vs. CPT. METHODS: A total of 193 cis women with PTSD related to childhood abuse and borderline personality disorder features were assessed using the Clinician-Administered PTSD Scale (CAPS) and the Barratt Impulsiveness Scale (BIS-10). Separate probit models and general linear models were applied to predict dropout and pre-to-post changes in PTSD severity (ΔCAPS) from total impulsivity and subscale scores, i.e. non-planning, attentional and motor impulsivity. RESULTS: Overall, dropout rates were higher for participants with higher baseline impulsivity scores (p = 0.049), particularly for those with higher non-planning impulsivity (p = 0.012). In participants randomized to CPT improvement in PTSD symptom severity (ΔCAPS) was negatively related to baseline total impulsivity (p = 0.021). In participants randomized to DBT-PTSD this relation was not significant. CONCLUSIONS: The results suggest that impulsivity may predict treatment outcomes. Specifically, patients with elevated impulsivity may be less likely to respond adequately to CPT. If replicated, these findings have implications for personalization of treatment.

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PubMed2026

Comparison of Keverprazan-based versus esomeprazole-based dual therapy for initial treatment of Helicobacter pylori infection: a prospective, multicenter, randomized controlled trial.

BACKGROUND: Keverprazan offers a new perspective for Helicobacter pylori eradication. This study compared 14-day keverprazan-amoxicillin therapy with esomeprazole-amoxicillin therapy to explore a superior treatment strategy. METHODS: This was a prospective, open-label, multicenter, randomized controlled trial in adult patients with treatment-naive H. pylori infection. Participants were randomly assigned to receive either 14-day of KA therapy (Keverprazan 20 mg b.i.d plus amoxicillin 1 g t.i.d) or 14-day of EA therapy (Esomeprazole 40 mg b.i.d plus amoxicillin 1 g t.i.d). The primary outcome was the H. pylori eradication rate. Secondary outcomes were the incidence of adverse events and patient adherence. RESULTS: A total of 264 patients were enrolled in the study. In the intention-to-treat (ITT) analysis, the eradication rates for the 14-day KA group and the 14-day EA group were 87.9% and 80.3%, respectively (p = 0.092); in the modified intention-to-treat (mITT) analysis, the eradication rates were 92.1% and 86.2%, respectively (p = 0.135); and in the per-protocol (PP) analysis, the eradication rates were 93.5% and 88.3%, respectively (p = 0.155). Non-inferiority was confirmed between the two groups (all p < 0.001). Adverse events and patient adherence were similar between the two groups. CONCLUSION: For treatment-naive H. pylori infection, the 14-day KA therapy is non-inferior to EA therapy. Given its good tolerability, pharmacogenomic independence, and potent acid suppression, KA is a rational first-line alternative to EA in the Chinese population.

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PubMed2026

CoLchicine for Treatment of OsteoArthritis of the Knee (CLOAK): Clinical and biochemical outcomes from a three-month double-blind, placebo-controlled study.

OBJECTIVE: Knee osteoarthritis (KOA) causes pain and progressive disability, but pharmacologic treatments are limited. Colchicine inhibits inflammation that might modulate KOA, but efficacy trials have yielded mixed results. We tested whether colchicine, without concurrent NSAIDs, improved KOA pain, function, synovial effusion size, and OA-associated inflammatory serum biomarkers. METHODS: Participants with symptomatic KOA and radiographic Kellgren-Lawrence grades 2/3 were randomized to receive three months of daily colchicine or placebo in a double-blind manner, with no concurrent NSAID use. The primary outcome was between-group change in visual analog score (VAS) for index knee pain. Secondary outcomes included changes in Knee Osteoarthritis Outcome Scores (KOOS), size (depth in millimeters) of sonographically-identified effusions, acetaminophen use, and changes in OA-related serum biomarkers. RESULTS: From baseline to end of study of 120 enrolled participants, no significant differences were observed in improvement of VAS pain, KOOS scores or effusion size. Subsets of participants with more severe VAS pain, worse radiographic disease, or higher hsCRP or serum urate levels at baseline also showed no significant clinical benefit from colchicine compared to placebo. In contrast to the clinical outcomes, colchicine treatment was associated with significant or trending improvement in multiple OA-related serum biomarkers including hsCRP and β-NGF (p < 0.05) and PGE2, IL-1ra, IL-8, and VEGF (p < 0.16). CONCLUSION: This double-blind placebo-controlled trial of colchicine for KOA failed to demonstrate improvement in pain, function, or synovial effusion size in comparison to placebo at three months. Early improvement in OA-associated inflammatory biomarkers suggests a possible longer-term clinical benefit. Clinical Trials Registration No NCT03913442.

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PubMed2026

Patient and hospital factors associated with disparities in acute stroke treatment in community and academic hospitals.

BACKGROUND: Systemic barriers may affect identification, emergency transportation (EMS), and care coordination for people with stroke. We assessed patient- and hospital-level factors for associations with pre-hospital and emergency department care. We compared trends for patients presenting to an academic medical center (AMC) versus community hospitals (CHs). METHODS: We conducted a retrospective cohort study at an AMC (Tufts Medical Center) with 542 patients aged ≥18 years hospitalized with acute ischemic stroke or transient ischemic attack between 1/1/2018-12/31/2020 who presented directly to AMC or presented to AMC as a transfer from initial contact CHs. Primary outcomes were EMS use, stroke code activation, door-to-CT time, and door-to-needle time. RESULTS: AMC patients identifying as non-Hispanic Asian (odds ratio (OR) = 0.25; 95% confidence interval (CI) = 0.13-0.47) and Hispanic (OR = 0.19; 95% CI = 0.05-0.72) and CH non-Hispanic Black/African-American patients (OR = 0.17; 95% CI = 0.05-0.62) were less likely to use EMS compared to non-Hispanic white patients. Patients with non-English primary language were less likely to use EMS (OR = 0.38; 95% CI = 0.23-0.63) compared to English-speaking patients in both hospital settings. CH Hispanic patients were less likely to have stroke code activation (OR = 0.24; 95% CI = 0.05-0.86) compared to non-Hispanic white patients. CH patients were less likely to have stroke code activation (OR = 0.12; 95% CI = 0.07-0.19), had 31% shorter door-to-CT time (95% CI = 15-43% shorter), and had 29% longer door-to-needle time (95% CI = 5-58% longer). CONCLUSION: Patient-level factors and hospital setting were associated with differences in acute care suggesting opportunities for community outreach on EMS use, interventions to alleviate language barriers, and a need to address systemic biases.

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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).

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PubMed2026

Novelty seeking and rapid symptom improvement across active and sham accelerated iTBS conditions: A pooled individual-patient data analysis.

INTRODUCTION: Major depressive disorder (MDD) is highly prevalent and often treatment-resistant. Accelerated intermittent theta burst stimulation (aiTBS) is a promising intervention for treatment-resistant depression (TRD), though outcomes vary. Personality traits have been examined in relation to rTMS outcomes, yet their role in aiTBS remains underexplored. This pooled individual-patient-data analysis of two randomized, sham-controlled trials examined associations between baseline Temperament and Character Inventory (TCI) traits and one-week symptom change, and whether they differed by condition. METHODS: The left dorsolateral prefrontal cortex was targeted for 20 sessions over 4 days. Personality was assessed with the TCI, depression severity with the 17-item Hamilton Depression Rating Scale (HDRS-17). TCI-symptom-change associations were examined with a robust linear mixed-effects model, adjusting for age, gender, repeated measurements, and study membership. RESULTS: 104 participants were included (M/F 45/59; mean age 40.9 ± 12.7; active/sham 50/54). The model yielded a Time × Novelty Seeking interaction (β = -1.70, p = 0.021): higher baseline Novelty Seeking was associated with faster symptom reduction, without a between-arm difference. However, the interaction did not survive Holm correction across 14 trait-interaction tests (adjusted p = 0.294) and is therefore exploratory. No other interaction reached the uncorrected threshold. CONCLUSIONS: Higher baseline Novelty Seeking showed a nominal association with faster symptom reduction, without a difference between active and sham conditions. Because it did not survive multiplicity correction and was not reproduced in within-arm analyses, it is preliminary and may reflect contextual or nonspecific processes. Independent replication is required before temperament assessment can be clinically informative.

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PubMed2026

Endovascular treatment after stroke beyond 24 h vs 6-24 h: a propensity score-matched cohort study.

BACKGROUND: Endovascular thrombectomy (EVT) is the standard treatment for acute ischemic stroke due to anterior circulation large vessel occlusion (LVO) within 6-24 h. However, the safety and feasibility of EVT for anterior circulation strokes beyond 24 h remain uncertain. METHODS: We conducted a retrospective cohort study of consecutive patients with anterior circulation LVO who underwent EVT at Changhai Hospital from 2018 to 2023. Patients were stratified into late (6-24 h) and very late (>24 h) windows. Propensity score matching (PSM) was performed to adjust for baseline imbalances, including age, sex, NIHSS, ASPECTS, occlusion location, perfusion parameters, and vascular risk factors. The primary outcome was functional independence (modified Rankin Scale [mRS] ≤ 2) at 3 months. Secondary outcomes included successful reperfusion (TICI 2b-3) and symptomatic intracranial hemorrhage (sICH). RESULTS: Among 1043 screened patients, 429 patients with anterior circulation LVO were included after exclusions, comprising 373 in the late window and 56 in the very late window. PSM yielded 42 matched pairs. Compared with the late window group, the very late window group showed no statistically significant differences in functional independence (54.8% vs. 57.1%; OR = 0.908, 95% CI 0.382-2.153, p = 0.830), successful reperfusion (88.1% vs. 92.9%; OR = 1.800, 95% CI 0.481-7.096, p = 0.460), sICH (2.4% vs. 9.5%; OR = 0.232, 95% CI 0.012-1.652, p = 0.200), intraprocedural complications (26.2% vs. 19.0%; OR = 1.508, 95% CI 0.540-4.362, p = 0.440), or postoperative complications (33.3% vs. 35.7%; OR = 0.900, 95% CI 0.363-2.219, p = 0.820). CONCLUSIONS: In this selected, single-center cohort of anterior circulation LVO patients undergoing EVT, treatment initiated beyond 24 h appeared to have comparable effectiveness and safety to treatment initiated within 6-24 h. Definitive evidence requires confirmation from adequately powered randomized controlled trials.

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PubMed2026

Hyperbaric oxygen for the treatment of traumatic incomplete spinal cord injury: a systematic review and meta-analysis of randomized controlled trials.

The therapeutic efficacy of hyperbaric oxygen therapy for traumatic incomplete spinal cord injury remains a subject of debate. To comprehensively evaluate the impact of hyperbaric oxygen on motor function, sensory function, and activities of daily living in patients with traumatic incomplete spinal cord injury, we conducted a systematic review and meta-analysis. We performed a comprehensive search across PubMed, Embase, the Cochrane Library, Web of Science, and major Chinese databases for randomized controlled trials published through June 2025. A total of 15 randomized controlled trials were included. The pooled results indicated that hyperbaric oxygen therapy significantly improved the American Spinal Injury Association motor score (mean difference = 10.30, 95% confidence interval: 7.70-12.90), the total American Spinal Injury Association sensory score (mean difference = 29.29, 95% confidence interval: 18.82-39.75), the American Spinal Injury Association light touch score (mean difference = 9.84, 95% confidence interval: 6.15-13.53), and the American Spinal Injury Association pinprick score (mean difference = 8.75, 95% confidence interval: 4.40-13.11). Furthermore, hyperbaric oxygen therapy was associated with significant enhancements in the Barthel Index (mean difference = 16.60, 95% confidence interval: 10.51-22.68) and the Functional Independence Measure (mean difference = 17.41, 95% confidence interval: 10.83-23.98). In conclusion, adjunctive hyperbaric oxygen therapy appears to improve motor function, sensory function, and activities of daily living in patients with traumatic incomplete spinal cord injury compared to conventional treatments alone. However, due to methodological limitations and potential publication bias in the included studies, these findings should be interpreted with caution, and further high-quality, multi-center randomized controlled trials are warranted.

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PubMed2026

Meta-analysis and pharmacoeconomic study of rasagiline versus selegiline in the treatment of Parkinson's disease.

OBJECTIVE: Given the persistent absence of direct head-to-head trials, this study aimed to evaluate the comparative efficacy, safety, and cost-effectiveness of rasagiline versus selegiline as early-stage monotherapy for Parkinson's disease (PD), informing clinical selection and healthcare policies in China. METHODS: A systematic search of PubMed, Embase, and the Cochrane Library identified randomized controlled trials (RCTs) up to April 2026. Focusing on short-term outcomes (10-16 weeks), an adjusted indirect treatment comparison (ITC) using placebo as a common anchor evaluated symptom improvement (UPDRS total scores) and adverse event (AE) incidence. For economic evaluation, a 2-year Markov model was constructed from a Chinese healthcare-system perspective. The incremental cost-effectiveness ratio (ICER) was calculated alongside robust sensitivity analyses. RESULTS: Ten RCTs (rasagiline: 6; selegiline: 4) were included. The ITC revealed no statistically significant differences between rasagiline and selegiline in short-term symptomatic relief (Mean Difference = -0.82, 95% CI [-2.08, 0.44], p = 0.203) or AE risk (Odds Ratio = 0.83, 95% CI [0.50, 1.38], p = 0.475). The overall evidence certainty was rated as moderate. Economically, the base-case simulation indicated rasagiline yielded a marginal benefit of 0.0088 QALYs over selegiline but incurred an additional 17,111.10 Yuan. This resulted in an ICER of 1,951,505.55 Yuan/QALY, substantially exceeding the conventional willingness-to-pay threshold. CONCLUSION: Supported by moderate-certainty evidence, rasagiline and selegiline provide comparable short-term efficacy and safety for early-stage PD monotherapy. However, at its current pricing, rasagiline is not cost-effective. Significant price reductions or definitive proof of long-term superiority are required to justify its economic value.

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PubMed2026

Cannabis and cannabinoids for the treatment of mental and substance use disorders and symptoms: A systematic review and meta-analysis of experimental and observational studies.

BACKGROUND: Interest in cannabinoids for mental and substance use disorders is increasing. We examined experimental and observational evidence for treating these disorders and their symptoms. METHODS: Systematic review and meta-analysis (PROSPERO CRD42023467536). We searched CENTRAL, MEDLINE, Embase and PsycINFO to May 2025 for studies of cannabinoids in adults (≥18 years) with ADHD, anxiety, depression, PTSD, psychosis or Tourette syndrome, or alcohol, cannabis, opioid or tobacco use disorders. Two reviewers screened, extracted and assessed quality using a risk-of-bias tool and GRADE. RESULTS: We included 82 experimental and 118 observational studies. In RCTs, cannabinoids reduced anxiety symptoms (SMD=-0.40; 95% CI: -0.57, -0.23; I²=90%) and, in one small trial, PTSD symptoms (SMD=-2.60; 95% CI: -4.58, -0.62; n=20), with trivial-to-no effect on depression (SMD=-0.20; 95% CI: -0.43, 0.04; I²=91.6%), ADHD, psychosis and Tourette syndrome. Much anxiety and depression evidence came from symptoms measured as secondary outcomes in other primary conditions. Cannabinoids worsened cannabis use disorder severity in one RCT (SMD=2.35; 95% CI: 1.49, 3.21), with no effect on craving or withdrawal; evidence for alcohol, opioid and tobacco use disorders was very limited. Observational studies suggested improvements but had high risk of bias. The only significant safety finding was increased withdrawals due to adverse events with THC (OR=2.78; 95% CI: 1.66, 4.65). Certainty was predominantly very low. DISCUSSION: The evidence base shows very low certainty, high heterogeneity and methodological limitations, and is insufficient to support cannabinoids as first-line treatment. Signals for anxiety and PTSD are limited by indirectness and low certainty; no benefit was evident for depression; THC-related safety signals warrant careful consideration.

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PubMed2026

Comparative efficacy of percutaneous vertebroplasty combined with minimally invasive pedicle screw fixation versus percutaneous vertebroplasty alone in the treatment of elderly osteoporotic vertebral compression fractures.

The study aimed to assess the comparative efficacy of percutaneous vertebroplasty (PVP) combined with minimally invasive pedicle screw fixation versus PVP alone in elderly patients with osteoporotic vertebral compression fractures (OVCF). Ninety-four elderly patients with OVCF were randomly classified into the control (47 patients) and combined (47 patients) groups. The control group received PVP, while the combined group received PVP combined with minimally invasive pedicle screw fixation. Perioperative indicators such as intraoperative blood lose, operative time, and hospitalization time were recorded. Pain was assessed using the VAS before and at baseline and 1, 3, and 7 days postoperatively. At 1 and 3 days postoperatively, Serum CRP levels, WBC, and neutrophil counts were measured postoperatively. Radiographic outcomes (vertebral height ratio and Cobb angle), ADL scores, JOA scores, and ODI were evaluated preoperatively and at 3 months post-operation. Postoperative complications were documented. Baseline characteristics were comparable. The combined group showed superior pain relief, vertebral height restoration, Cobb angle correction, functional recovery, and reduced inflammatory markers (CRP, WBC, neutrophils) postoperatively (all P < 0.05). Blood loss and hospital stay were shorter in the combined group, though operative time was longer (P < 0.05). Complication rates did not differ significantly (P > 0.05). PVP combined with minimally invasive pedicle screw fixation yields better outcomes in elderly OVCF patients by enhancing pain control, vertebral height, and functional recovery without increasing perioperative risk.

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PubMed2026

A randomized trial of omega-3 fatty acids plus inositol versus N-acetylcysteine for the treatment of depression and mania in emotionally dysregulated youth age 5-17 with and without autism traits.

The aim of this study was to assess the effectiveness of the nutraceutical treatments combined omega-3 fatty acid plus inositol (O3I) versus N-acetylcysteine (NAC) in children and adolescents with emotional dysregulation and the impact of the co-occurrence of autism traits (AT). Participants were male and female children (5-17) with emotional dysregulation and the presence/absence of AT, as defined by Child Behavior Checklist score, randomized to receive open-label O3I (1020 mg EPA and 1000-2000 mg Inositol) or NAC (1800-2700 mg) daily for 6 weeks. Clinicians measured severity and improvement of depression and mania with the NIMH Clinical Global Improvement Scale (CGI). Parents completed Parent-Youth Mania Rating Scale (P-YMRS) and Children's Depression Inventory (CDI). Both O3I and NAC resulted in modest improvements in mania and depression and did not differ significantly in between group comparison in their effectiveness. Participants taking O3I, but not NAC, demonstrated statistically significant within group improvement in depression per CDI. Participants taking NAC had a greater decrease in P-YMRS scores versus O3I, but the difference did not reach statistical significance. In the presence of AT, NAC was more effective than O3I for mania but not for depression. Further, participants taking NAC, but not O3I, demonstrated significant within group improvement in SRS and BRIEF scores. These results suggest that O3I and NAC may be beneficial for mania and depression in youth, with trends towards O3I more effective for depression and NAC more effective for mania. The presence of AT in youth with emotional dysregulation may moderate the impact of NAC.

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PubMed2026

Characterization of local tolerability of TV-46000, a long-acting subcutaneous formulation of risperidone for the treatment of schizophrenia.

TV-46000 is a long-acting injectable antipsychotic (LAI) approved for the treatment of adults with schizophrenia and bipolar I disorder. LAIs like TV-46000 can improve adherence and reduce relapse in patients with schizophrenia; however, injection site reactions (ISRs) can contribute to LAI discontinuation. ISRs with TV-46000 treatment were characterized using data from two phase 3 trials of patients with schizophrenia (RISE [NCT03503318], SHINE [NCT03893825]) and a phase 1 study of patients with schizophrenia or schizoaffective disorder. Patients in the pooled safety population (aged 16-67 years) from RISE and SHINE (n = 525 TV-46000, n = 179 placebo) received 4554 TV-46000 injections and 2721 placebo injections. ISRs were reported in 19 % (n = 102) of patients who received TV-46000, corresponding to an exposure-adjusted event rate (EAER)/100 patient-years of 48.67. ISRs led to 9 (1.7 %) treatment discontinuations of TV-46000. The most frequently reported ISR adverse events were injection site pain (EAER, 15.38, n = 36 [7 %]) and injection site nodule (EAER, 12.01, n = 35 [7 %]). ISR frequency and pain and nodule adverse event frequency decreased after the first injection. In the phase 1 study (n = 99), mean injection site pain scores were highest immediately after injection, showed a notable decrease within 10 min of injection, and further decreased within 1 h after injection. In conclusion, for >4500 injections evaluated, ISR rates with TV-46000 were modest. Most ISRs were mild or moderate and rarely led to treatment discontinuation. Results support the favorable tolerability of TV-46000 as a treatment for schizophrenia in adults.

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PubMed2026

Aneurysmal subarachnoid hemorrhage care in a middle-income public healthcare system: A real-world neurocritical care cohort.

BACKGROUND AND PURPOSE: Although aneurysm treatment capacity has expanded worldwide, outcomes after aneurysmal subarachnoid hemorrhage (aSAH) remain strongly influenced by neurocritical care (NCC) delivery, referral pathways, and access to specialized treatment. Contemporary data describing real-world aSAH care in resource-limited healthcare systems remain scarce. We aimed to characterize treatment patterns, NCC delivery, complications, and outcomes in a large Brazilian public referral center. METHODS: This retrospective cohort study included consecutive adults with confirmed aSAH admitted between June 2018 and March 2022 to a high-volume Brazilian tertiary referral center. Only patients admitted within five days of symptom onset were included. Demographic, clinical, radiological, treatment, complication, and outcome data were extracted from institutional records. Primary outcomes were in-hospital mortality and 3-month functional outcome assessed by the modified Rankin Scale (mRS). RESULTS: Seventy-four patients were included. Disease severity was high, with 45% presenting WFNS grades 4-5, 73% modified Fisher grade 4 hemorrhage, and 64% hydrocephalus. Endovascular treatment was performed in 73% of cases, and median time from admission to aneurysm treatment was 1 day. Despite early treatment capability, only 28% of patients were admitted to an ICU within 48 h, while 38% never received ICU care. Delayed cerebral ischemia occurred in 43%, radiologic vasospasm in 58%, ventriculitis in 22%, and infectious complications in 57%. External ventricular drainage was required in 42%, and vasoactive drugs were used in 85%. In-hospital mortality was 42%, and 66% had unfavorable 3-month outcomes (mRS 4-6). CONCLUSIONS: This real-world cohort highlights the substantial neurocritical care burden of aSAH in a middle-income public healthcare system. Despite timely access to definitive aneurysm treatment, patients experienced frequent neurological and systemic complications, emphasizing that contemporary aSAH care extends well beyond aneurysm occlusion.

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PubMed2026

The emerging applications of JAK inhibitors in dermatology - a systematic review.

BACKGROUND: Janus kinase (JAK) inhibitors are established treatments for selected dermatologic conditions, but their off-label use has expanded across refractory skin diseases. METHODS: We systematically searched MEDLINE, Embase, and Web of Science from inception to October 1, 2025, for studies reporting off-label JAK inhibitor use in dermatologic disorders beyond approved or late-phase trial indications. RESULTS: Of 9,182 records screened, 277 studies met the inclusion criteria, comprising 210 case reports, 55 case series, and 12 retrospective studies involving 764 patients. Owing to substantial clinical heterogeneity, findings were narratively synthesized using a structured disease-family framework. Off-label use most commonly involved lichenoid, neutrophilic, and granulomatous dermatoses. Overall, 725/764 (94.88%) patients experienced clinical benefit, including complete or near-complete response in 209/764 (27.35%) and significant or partial improvement in 516/764 (67.53%). Thirty-five patients (4.58%) showed no clinical change, and four (0.52%) experienced disease worsening. A total of 154 adverse events were reported, most commonly with tofacitinib; most were mild to moderate, although six were serious and 25 resulted in treatment discontinuation. CONCLUSION: JAK inhibitors demonstrate promising therapeutic potential across a broad spectrum of refractory dermatological diseases. The predominance of uncontrolled case-based evidence, heterogeneous dosing, and frequent combination therapy limits attribution of efficacy and safety to JAK inhibitor monotherapy. Prospective controlled studies are needed to better define their therapeutic role.

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PubMed2026

Examining early-phase symptom trajectories in interpersonal psychotherapy versus antidepressant medication for adults with depression: A dynamic time warp network analysis.

BACKGROUND: Depression is characterized by substantial symptom heterogeneity, which is often concealed when examining total severity scores. Analyzing symptom-level change can improve our understanding of treatment effects and recovery processes. This study, therefore, examined dynamic symptom networks during early-phase interpersonal psychotherapy (IPT) and selective serotonin reuptake inhibitor (SSRI) antidepressant treatment, assessing patterns of symptom change across as well as differences between treatments. METHODS: Using weekly item-level Hamilton Depression Rating Scale (HAM-D) data from a randomized clinical trial comparing IPT and SSRIs for adults with depression, this preregistered study examined symptom trajectories in the first six weeks of treatment with Dynamic Time Warping (DTW). RESULTS: Depressive symptom trajectories and DTW-based symptom networks were largely similar for IPT and SSRI. In both conditions, changes in somatic symptoms of anxiety and middle insomnia tended to precede improvements in depressed mood. CONCLUSIONS: Early symptom change may occur outside the core affective domain, underscoring the importance of monitoring symptoms broadly. Symptom-level patterns may reflect patients' stage of recovery and provide clinically relevant information beyond total severity scores. The absence of differences in improvement patterns between IPT and SSRI suggest few indications for treatment selection based on baseline symptom profiles. Future research should replicate and extend these findings to subsequent treatment phases using more frequent assessments and a broader range of interventions.

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PubMed2026

Long-term outcomes of non-operative compared to operative management of acute uncomplicated appendicitis - a systematic review and meta-analysis.

BACKGROUND: We evaluated long-term outcomes of non-operative management (NOM) versus surgical management of acute uncomplicated appendicitis. METHODS: Systematic review of studies comparing NOM versus surgery with ≥2 years follow-up. Primary outcome was long-term failure rate. RESULTS: 9/1635 studies were included (3 RCTs; 6 non-RCT studies), involving 3883 patients; 5 were in pediatric populations. Median follow-up was 33.6 (range 24-312) months. NOM pooled long-term failure rate was 38.9% (95% CI: 31.1%-46.7%), increasing to 44.4% (95% CI: 41.4%-47.4%) in RCTs. Pooled appendectomy rate after NOM was 36.3% (95% CI: 28.9%-43.7%). Incidence of appendiceal neoplasms was approximately 0.3%. Non-operative management had cost savings of €1535 (95% CI: -€1892 to -€1178) versus surgery. CONCLUSIONS: NOM of acute uncomplicated appendicitis was associated with high long-term failure rates and significant risk of subsequent appendectomy.

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