Patients with atrial fibrillation who experience acute ischemic stroke (AIS) are at high risk of early recurrent ischemic stroke or systemic embolism. Timely initiation of anticoagulation is essential to prevent subsequent ischemic events but must be carefully balanced against the risk of hemorrhagic transformation or intracranial hemorrhage. Historically, early anticoagulation therapy with heparin or vitamin K antagonists for AIS has shown uncertain benefits. The safety and efficacy of early initiation of non-vitamin K oral anticoagulants, initially suggested by observational studies, have been confirmed by randomized controlled trials and further supported by an individual patient data meta-analysis. However, uncertainties remain in specific populations, including those with severe stroke, hemorrhagic transformation, and Asian patients, who are at an increased risk of intracranial bleeding and are underrepresented in clinical trials.

Chest trauma often causes respiratory impairment and carries substantial mortality, particularly among intubated patients. Although guidelines recommend noninvasive ventilation (NIV) for hypoxemic respiratory failure, high flow nasal cannula (HFNC) is increasingly used despite limited comparative evidence. The objective was to compare the effects of conventional oxygen therapy (COT), HFNC, and NIV on escalation of respiratory support and in-hospital outcomes in adults with hypoxemic respiratory failure after chest trauma. We conducted a systematic review and network meta-analysis registered in UMIN (UMIN000059126) and reported according to PRISMA-NMA. MEDLINE, Cochrane Central, Cumulative Index to Nursing and Allied Health Literature, WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov were searched from January 2000 to July 2025. Randomized controlled trials and high-quality observational studies were eligible if they compared at least two of COT, HFNC, and NIV in adults with hypoxemia due to chest trauma. The primary outcome was escalation of respiratory support; secondary outcomes were in-hospital mortality and length of hospital stay. A random-effects frequentist network meta-analysis was performed. Four studies met eligibility criteria (three randomized trials and one observational study), including 3,270 patients: 1,465 received NIV, 1,613 HFNC, and 192 COT. Compared with COT, NIV was associated with a lower risk of escalation of respiratory support [odds ratio (OR), 0.42; 95% CI, 0.20-0.85] and a lower escalation risk than HFNC (OR, 0.72; 95% CI, 0.58-0.89). HFNC showed uncertain benefit relative to COT (OR, 0.58; 95% CI, 0.29-1.16). NIV was also associated with lower in-hospital mortality and shorter hospital stay than both COT and HFNC. Reported device-related and clinical complications were uncommon. In adults with hypoxemic respiratory failure after chest trauma, NIV appears more effective than HFNC and COT in preventing escalation of respiratory support and improving in-hospital outcomes.(J Trauma Acute Care Surg. 2026;00:000-000. Copyright © 2026 Wolters Kluwer Health, Inc. All rights reserved.). Systematic review/meta-analyses; Level II.

This paper presents a novel framework for optimizing the locations and sizes of urban air mobility (UAM) vertiports. Unlike previous studies that focused on maximizing accessibility and potential demand, our approach emphasizes the social acceptance of UAM. A vertiport location problem with social benefits (VLPSB) that maximizes social benefits while considering practical constraints such as demand and noise pollution is proposed. Additionally, we introduce a stepwise vertiport location optimization problem (S-VLPSB) to address the demand uncertainty in UAM by solving the VLPSB sequentially. A case study and a comparative study for Jeju Island in South Korea, a representative scenario based on actual data, demonstrate the validity of the framework and discuss the impact and implications of key parameter variations.

Little is known about Mycoplasma genitalium's (MG) natural history in the throat and the rectum. Methods: Men who have sex with men (MSM) enrolled in a longitudinal cohort study on the natural history of extragenital gonorrhea and chlamydia. Men self-collected pharyngeal and rectal specimens weekly and completed electronic symptom and sexual behavior diaries for 48 weeks. Prevalent infections were detected on the first week of testing; incident infections were ≥2 consecutive weeks of positive specimens after a negative test. We calculated duration using Kaplan-Meier analysis. Of 140 enrolled MSM, 112 participated and 108 submitted samples on week one. Ten (9.3%) had prevalent rectal MG; there were fifteen incident rectal MG infections (incidence 19.8 per 100 person years (py), 95% CI:11.5-34.1 per 100 py). Rectal MG had a median duration of 42 weeks (95% CI: 7.3 weeks - undefined); most infections (60%) were entirely asymptomatic. Four (3.7%) participants had prevalent pharyngeal infections. Fourteen incident pharyngeal infections arose (incidence 17.5 per 100 person years, 95% CI: 9.9-30.8 per 100 py). Pharyngeal MG had a median duration of 12 weeks (95% CI: 6.3 weeks - undefined); symptoms were rare (6%). Rectal and pharyngeal MG was common in this cohort. Half of the rectal MG infections persisted for nearly a year; many remained positive on week 48 suggesting persistence beyond one year. Pharyngeal infection persisted three months. The absence of symptoms or other morbidity in most infections suggests testing for MG at these sites would have uncertain individual benefit.

To report outcomes of pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling for extensive macular schisis in choroideremia and provide surgical insights. Retrospective case series of five eyes from four patients with choroideremia and extensive macular schisis who underwent PPV with ILM peeling at a single tertiary center between 2011 and 2025. Data collected included pre- and post-operative best-corrected visual acuity (BCVA), surgical technique, spectral-domain optical coherence tomography (SD-OCT) imaging, intraoperative findings, and post-operative complications. All five eyes showed complete resolution of macular schisis on SD-OCT without foveal retinal pigment epithelium atrophy. BCVA improved in all cases. Intraoperative challenges included retinal fragility, peripheral schisis-like changes, and difficulty with ILM visualization and adherence. No iatrogenic retinal breaks or detachments occurred. Vitrectomy for extensive macular schisis in choroideremia can yield favourable anatomical and functional outcomes but requires tailored techniques to address retinal fragility and minimize iatrogenic trauma. Extensive macular schisis is a common end stage feature of choroideremia that is frequently missed as patients are no longer being followed up. The schisis however, can detach the small, remaining island of vision leading to potentially treatable vision loss. Due to retinal fragility, surgical intervention is traditionally considered high risk and of uncertain benefit. Pars plana vitrectomy with internal limiting membrane peeling and tailored surgical strategies can achieve favourable anatomical and functional outcomes in choroideremia patients.

Polypharmacy and long-term preventive medication use are common in frail older adults with limited life expectancy, despite uncertain benefits and potential risks. This systematic review and meta-analysis synthesized evidence on the effect of deprescribing preventive medications (antihypertensives, statins, anticoagulants, and antidiabetic agents) compared to continuation on clinical, physiological, safety, and patient-centered outcomes among older adults with advanced frailty, dementia, or limited life expectancy. PubMed, Embase, Cochrane Library, Web of Science, CINAHL, and ProQuest Dissertations & Theses Global were searched for eligible randomized controlled trials and observational studies. The primary outcome was all-cause mortality. Secondary outcomes were hospitalization, major adverse cardiovascular events (MACE), changes in blood pressure, risks of fractures and falls, and quality of life. Data were pooled (relative risk [RR] or mean difference or standardized mean difference) using random-effects models (RevMan version 5.4). The evidence certainty was evaluated by the GRADE framework (PROSPERO ID: CRD420251147086). From 10,397 records, 15 studies (> 33,000 participants) were included. Overall, deprescribing was not associated with increased risk of all-cause mortality (RR: 1.15, 95% CI: 0.98–1.35, I2: 93%), hospitalization (RR: 0.93, 95% CI: 0.82–1.07, I2: 68%), or MACE (RR: 1.37, 95% CI: 0.70–2.70, I2: 95%) (certainty: very low GRADE). Deprescribing was also not associated with increased risks of fracture, fall, or deterioration of quality of life, but with slightly increased systolic blood pressure (deprescribing antihypertensives). Deprescribing preventive medications in frail or palliative older adults was not associated with worse outcomes; however, evidence certainty was very low, and further studies are needed.

A BSTRACT Objectives: Cardiovascular disease is the leading cause of mortality in dialysis patients. While clinical trials have suggested uncertain benefit of statin therapy in this population, several large-scale observational studies have reported an association between statin use and reduced all-cause mortality. To further explore this issue, we aimed to assess the effectiveness of statin therapy in dialysis patients by synthesizing real-world data. Materials and Methods: We systematically searched PubMed and Embase for observational studies comparing adult statin users to nonusers in maintenance dialysis patients. Outcomes included all-cause mortality, cardiovascular death, stroke, myocardial infarction (MI), and major adverse cardiovascular events (MACE). Results: Nineteen studies with 310,370 dialysis patients were included. Statin use was associated with a lower risk of all-cause mortality (adjusted hazard ratio [aHR], 0.82; 95% confidence interval [CI], 0.77–0.87) and cardiovascular death (aHR, 0.83; 95% CI, 0.74–0.94). However, sensitivity analyses showed attenuated associations (aHR, 0.92; 95% CI, 0.89–0.96 for all-cause mortality; aHR, 0.90; 95% CI, 0.82–0.99 for cardiovascular death). No significant associations were observed between statin use and the risk of stroke, MI, or MACE. Conclusion: Statin therapy modestly reduced the risk of all-cause and cardiovascular mortality in patients undergoing maintenance dialysis but was not associated with a reduced risk of stroke, MI, or MACE.

Precision prevention refers to the use of data-intensive technologies to detect early indicators of disease and risk factors at the individual level. Precision prevention is not just a policy vision for a distant future but a development currently gaining momentum through wearables and self-tests marketed directly to consumers. We critically analyze one of the applications already on the market, namely detection of asymptomatic atrial fibrillation via smartwatches. We examine the promises made by manufacturers of smartwatches in relation to perspectives of general practitioners (GPs) in Denmark, who experience that new opportunities for disease prevention often come with new challenges. As one informant termed it, heart rate notifications are a form of "unauthorized screening" with uncertain benefits for individual patients and the healthcare system. The case of device-detected asymptomatic atrial fibrillation illustrates how precision prevention, via wellness technologies, can lead to a temporal disruption of evidence. We use this term to highlight the concern that evidence becomes the result of implementation, rather than the basis for it, thus turning consumers into experimental research subjects. The case of heart rate notifications also illustrates how the proactive approach to disease prevention, promoted by the wellness technology industry, drives a need for reactive research evaluating the benefits and harms of detection after the fact. We call for more attention to how big tech expansionism impacts the organization of health care and health research, as well as how the wellness technology industry shapes our understanding of disease and health.

Long-term psychological treatments are recommended for people with personality disorder. Brief interventions are increasingly delivered but are of uncertain benefit. We aimed to investigate the effectiveness of a brief individual psychological intervention for people with probable personality disorder over a 12-month period. The Structured Psychological Support (SPS) study was a multicentre, researcher-masked, randomised controlled superiority trial, conducted in seven mental health Trusts in England: Avon and Wiltshire Mental Health Partnership National Health Service (NHS) Trust, Central and North West London NHS Foundation Trust, Coventry and Warwickshire Partnership NHS Trust, Derbyshire Healthcare NHS Foundation Trust, Lincolnshire Partnership NHS Foundation Trust, Mersey Care NHS Foundation Trust, and Oxford Health NHS Foundation Trust. Participants were aged 18 years or older and had probable personality disorder identified by meeting a threshold of 4 or more on the Standardised Assessment of Personality Abbreviated Scale. We excluded those who: did not consent; had a co-existing psychotic disorder; or were already receiving psychological treatment. We assessed whether participants met criteria for borderline personality disorder using the Structured Clinical Interview for Axis II Personality Disorders and whether they had co-existing complex post-traumatic stress disorder using the International Trauma Questionnaire. We randomly assigned participants to up to ten sessions of SPS plus treatment-as-usual or enhanced treatment-as-usual (allocation ratio 1·15:1), using an independent remote system. Researchers assessing outcomes were masked to group allocation. SPS comprises up to ten individual sessions of personalised psychological support, which includes psychoeducation and psychological skills derived from evidence-based treatments (dialectical behaviour therapy and mentalisation-based treatment). Sessions were usually delivered on a fortnightly basis by staff with previous experience of working with people with personality disorder. The primary outcome was social functioning at 12 months measured using the Work and Social Adjustment Scale (WSAS). Data were analysed using multilevel mixed effects general linear regression on an intention-to-treat basis. We used multiple imputation to address missing outcomes. We undertook a parallel health economic evaluation, which included cost-effectiveness and cost-utility analyses. People with lived experience were involved in the design of the research and in the writing process. The trial was prospectively registered (ISRCTN13918289) and is now complete. Between Feb 7, 2023, and Jan 31, 2024, 569 potential participants were referred for study inclusion, 34 were deemed ineligible, 56 declined to participate, and 127 were not approached. 352 potential participants provided consent, of whom 16 were deemed ineligible or withdrew. 336 participants were randomly assigned to either SPS (n=180) or treatment-as-usual (n=156). 251 (75%) participants were female, 75 (22%) were male, and ten (3%) were non-binary or other. The mean age was 34·8 years (SD 13·2; range 18-68) and 281 (84%) participants were White. 152 (84%) participants in the SPS group and 132 (85%) in the control group completed the 12-month follow-up. There was no difference between groups for the primary outcome of WSAS score (standardised coefficient 0·12 [95% CI -2·14 to 2·38]; p=0·92). The probability that SPS is cost-effective was 0·34-0·39. There were 36 serious adverse events affecting 17 participants in the SPS group and 16 in the treatment-as-usual group. None were judged to be related to study procedures. Two study participants died during the 12-month follow period, both in the SPS group. We found no difference in social functioning over the course of 1 year among people offered a brief psychological intervention, and no evidence of cost-effectiveness. These data highlight the importance of improving access to longer-term evidence-based psychological treatment programmes for people with personality disorder. National Institute for Health and Care Research.

Prognosis of Isolated Cervical Node Recurrence After Esophagectomy With Two-Field Lymphadenectomy for Esophageal Squamous Cell Carcinoma.

Abstract Background: Breast MRI is routinely considered at initial diagnosis to evaluate extent of disease, multicentricity, and contralateral disease in the non-metastatic setting, despite randomized data (e.g., COMICE & MONET) showing little impact on re-excision rates or long-term outcomes. In addition to time delays, each scan may expose patients to out-of-pocket expenses that compound “financial toxicity,” a quality-of-life domain now tracked by ASCO and NCCN. We audited all first-episode breast MRIs at a large community system during 2024 to clarify the economic burden. Methods: Retrospective billing data of all breast cancer MRI scans (ICD-10 C50.x code present in at least 1 of the first 5 diagnosis fields) performed in calendar-year 2024 at a community hospital system was analyzed in this IRB approved study. Cases were included if they had both Hospital (HB) and Professional Billing (PB) available. Only the “initial episode” MRI for each patient, defined as the earliest service date, was used. Primary endpoint was the posted “Patient Payment Amount”. Descriptive statistics including Spearman, Kruskal-Wallis and chi2 were performed using Python 3.11 (pandas, scipy) Results: A total of 630 patients underwent a breast MRI in 2024. There was no difference in MRI distribution by service month. CPT code 77049 was billed in 95.4% of scans. Payer grouping included 53.0% Commercial, 32.7% Medicare, 11.7% ACA Marketplace, and 2.7% Military / Self-Paid / Other. Of all “Net Charges”, patients were liable for 13.4 %, insurers covered 75.4 %, and the hospital system had a gap of 11.2 %. For PB, 98.3 % of patients had a $0 copay, and among the 1.7% who did owe, median out-of-pocket responsibility was $94 (IQR $34-$100). The upper 10% of payers owed >$135, and the highest bill was $177 (skew = 0.46). For HB, 63.2% had $0 copay, and among the 36.8% who did owe, median out-of-pocket responsibility was $327 (IQR $171-$648). Ten percent of payers owed >$1,300, and the highest bill was $4,878 (skew = 2.8). For the combined PB + HB exposure, 64.0% of patients had a net $0 copay (including 1.3 % with small credits). Among the 36.0 % who owed anything, median out-of-pocket responsibility was $326 (IQR $174-$645). The upper 10 % of payers owed >$1,290, and the highest total bill was $4,878 (skew = 2.8). Patient responsibility did not show a consistent deductible effect: the proportion of $0 visits rose from 46% in January to 70% in December (Spearman p = 0.07), yet mean liability among paying patients fluctuated throughout the year (p = 0.32). Patient cost sharing with $0 co-pay by Payer class varied from 33.8% for ACA Marketplace, 49.7% for Commercial, 50% Military, 93.2% Medicare, and 100% for Medicaid, Self-Paid, and Other. Among patients who incurred >$0 liability, median responsibility was highest in Commercial plans ($453.09), followed by ACA Marketplace ($184.67), Medicare ($70.81), and Military ($30.50). Conclusions: Patient-level "financial toxicity" from an initial staging breast MRI is relatively minimal in our system—63 % of patients paid nothing and the remainder faced a median $327, almost entirely from the technical fee. These findings reassure clinicians that ordering a breast MRI seldom imposes a direct out-of-pocket burden on patients, though up-front cost counselling is important to prevent the rare but substantial financial surprises we identified. Cost-sharing burden fell mainly on ACA Marketplace and Commercially insured patients; Medicare and Medicaid beneficiaries were largely shielded. In a value-based oncology landscape, the decision to order a staging breast MRI should weigh its uncertain clinical benefit against not merely the patient’s copay at the point of care, but also system-level costs of both the hospitals that absorb charity-care write-offs and occasional under-collections, and the payers that cover the bulk of charges. Citation Format: C. Dvorak, H. Saunders, T. Dvorak, J. Smith. Patient Out-of-Pocket Exposure from Initial Staging Breast MRI: Quantifying Financial Toxicity in Breast Cancer Care [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-11-04.

Our perspective addresses one of the most pressing and timely debates in contemporary neurology and health policy: whether the recent approval of anti-amyloid monoclonal antibodies for Alzheimer's disease should extend to all individuals with mild cognitive impairment (MCI; a large population of tens of millions of individuals worldwide mainly represented in Countries with aged population) who test positive for amyloid biomarkers, despite wide variability in prognosis and therapeutic response and the epidemiological demonstration that only about half of them manifest symptoms of dementia. The manuscript highlights three central themes. First, while epidemiological and meta-analytic data confirm that MCI significantly increases the risk of dementia, more than half of affected individuals-many of whom are biomarker-positive for amyloid/tau-do not progress to dementia even over long- term follow-up. Second, recently approved anti-amyloid therapies, although representing a landmark in disease-modifying treatments, carry high costs, non-negligible risks (particularly amyloid-related imaging abnormalities), and uncertain long-term real-world benefits. Third, indiscriminate prescription of these agents risks exposing large numbers of subjects to unnecessary harm while placing unsustainable burdens on healthcare systems. We argue that the field should urgently move to identify and validate accurate and sustainable instruments for risk-stratified treatment pathways, integrating genetic, clinical, neuropsychological, neuroimaging, and fluid biomarker data including risk and resilience factors to refine prognostication. In addition, we call on the scientific community, journals, and policymakers to foster dialog that bridges neurology, geriatrics, bioethics, health economics, and patient advocacy, so that clinical innovation is matched by ethical responsibility and equitable implementation.

Routine surveillance for vancomycin-resistant enterococci (VRE) colonization remains the standard practice in many intensive care units. However, in high-acuity pediatric intensive care units (PICUs), where clinical VRE infections are uncommon, universal screening may impose substantial financial and operational burdens with uncertain clinical benefits. This study evaluates the necessity and value of universal VRE surveillance by describing the clinical characteristics and risk profiles of asymptomatic VRE-colonized patients in a newly established, high-acuity, 54-bed PICU. This single-center, retrospective cohort study included all patients with positive admission or weekly rectal VRE screening cultures between October 2023 and October 2024. Demographic, clinical, microbiologic (including species identification) and outcome variables were analyzed. Among 1270 PICU admissions, 74 patients (5.8%) were colonized with VRE; 42 (56.8%) were positive on admission and 32 (43.2%) acquired colonization during hospitalization. Enterococcus faecium was the predominant species (97.3%). Despite frequent exposure to recognized risk factors, including central venous catheters (79.7%), urinary catheters (77.0%), prolonged PICU stays and carbapenem exposure (62.2%), no patient developed a clinical VRE infection. In this high-acuity PICU with robust infection prevention infrastructure, VRE colonization, including colonization with high-risk E. faecium strains, did not progress to clinical infection. These findings suggest that in high-acuity PICUs with established infection control excellence, the clinical yield of universal VRE screening may be marginal compared with its operational costs, supporting a transition toward targeted, risk-based surveillance.

Abstract Background Colorectal cancer (CRC) is a leading cause of cancer-related death in older adults, particularly those with a history of colon polyps. However, surveillance guidance beyond age 75 is lacking. As a result, many individuals aged 75–84 with prior polyps continue to undergo colonoscopies despite uncertain benefit. The Fecal Immunochemical Test (FIT) may provide a safer alternative for surveillance in this population. Determining whether FIT can reliably exclude advanced neoplasia could reduce unnecessary colonoscopies and optimize the use of endoscopy resources. Aims This interim report evaluates the feasibility of FIT kit collection among older adults undergoing surveillance colonoscopy and provides preliminary data on the negative predictive value (NPV) of FIT for high-risk polyps (HRP) or CRC in this population. Methods This study is a prospective study aiming to recruit 417 patients aged 75–84 with a history of prior polypectomy who are already scheduled for surveillance colonoscopy at London Health Sciences Centre and St. Joseph’s Health Care London. Participants are asked to complete a FIT prior to their scheduled colonoscopy. FIT results do not influence clinical care, and all participants undergo colonoscopy as planned. The primary outcome is the NPV of FIT for detecting CRC or HRP, defined as polyps ≥10 mm, ≥3 adenomas, tubulovillous adenoma, high-grade dysplasia, or sessile serrated polyps. Results To date, 82 patients have been recruited, of whom 1 has passed away. The FIT kit return rate was 69.1% (56/81), with 6.2% testing positive (5/81). Among these 56 participants, 38 have completed colonoscopies with pathology results available; none were found to have CRC. Of these 38 participants, 30 had negative FIT results with no HRP identified on colonoscopy, while 5 had negative FIT results but were found to have HRP, yielding a preliminary NPV of 85.7% for FIT in detecting HRP. One participant had a positive FIT with HRP confirmed, and two had positive FIT results without HRP on colonoscopy. Stratifying by history, 14 participants had a history of HRP and 24 had a history of low-risk polyps (LRP). Among those with prior HRP, the NPV was 72.7% (8 with FIT-/HRP- and 3 with FIT-/HRP+). Among those with prior LRP, the NPV was 90.9% (20 with FIT-/HRP- and 2 with FIT-/HRP+). No serious adverse events have been reported to date. Conclusions Preliminary data demonstrate that FIT kit collection is feasible in older adults undergoing surveillance colonoscopy and suggest a high NPV of FIT, particularly among those with a history of low-risk polyps. These findings support FIT as a reasonable alternative to colonoscopy for guiding surveillance in this population. Continued recruitment will allow for more precise estimates and further assessment of its clinical implementation. Funding Agencies None

Anticancer drugs should make patients live longer and/or feel better. Ideally, endpoints of cancer randomized controlled trials (RCT) should demonstrate that a drug leads to an increase in overall survival and/or improvement in quality of life. With the aim of including smaller numbers of patients, running shorter trials and thus getting new drugs to patients faster, cancer RCT are increasingly using (putative) surrogate endpoints. However, changes in surrogate endpoints often do not reliably predict improvements in overall survival and/or quality of life. Furthermore, especially in later lines of cancer treatments or in cancer patients with a short life expectancy, use of surrogates hardly speeds up the availability of novel therapies but does increase the advent of costly toxic drugs with uncertain benefit, thereby harming both patients and society. In myelofibrosis, spleen response has extensively been used as a surrogate for clinical outcome. In this review we argue that there is no convincing evidence for the use of spleen response or other surrogate endpoints in myelofibrosis, and that the use of surrogate endpoints in RCT in myelofibrosis should be avoided altogether.

Uncomplicated Choledocholithiasis in Elderly Patients: A Target Trial Emulation Comparing Observation and Endoscopic Retrograde Cholangiopancreatography.

Confirmatory testing to identify lateralizing primary aldosteronism (PA) is of uncertain benefit. Blinded clinical trial where patients with high-risk features for PA underwent the seated saline suppression test (SSST). All patients received adrenal vein sampling, where lateralization was defined by an aldosterone/cortisol ratio ≥3:1 comparing the dominant versus the nondominant sides. The primary outcome was the overall diagnostic accuracy of the SSST in identifying lateralizing PA using postinfusion aldosterone concentrations of ≥140 pmol/L (5.0 ng/dL) and ≥280 pmol/L (10.1 ng/dL) with immunoassay, and ≥162 pmol/L (5.8 ng/dL) with liquid chromatography/tandem mass spectrometry. A total of 160 patients completed the trial. Lateralizing PA was diagnosed in 98 patients (61.3%). The overall diagnostic accuracy of the SSST using an aldosterone cutoff of ≥140 pmol/L (5.0 ng/dL) and ≥280 pmol/L (10.1 ng/dL) was 64.4% (95% CI, 56.4-71.8) and 67.5% (95% CI, 59.7-74.7), respectively. A positive result was equivocal at the lower cutoff of ≥140 pmol/L (5.0 ng/dL; positive likelihood ratio, 1.1 [95% CI, 1.0-1.3]) and minimally informative at the higher cutoff of ≥280 pmol/L (10.1 ng/dL; positive likelihood ratio, 1.9 [95% CI, 1.3-2.7]). Negative results modestly ruled against lateralization using cutoffs of ≥140 pmol/L (5.0 ng/dL) and ≥280 pmol/L (10.1 ng/dL; negative likelihood ratio, 0.3 [95% CI, 0.1-0.9]; and 0.5 [95% CI, 0.3-0.7], respectively). The SSST properties were similar with liquid chromatography/tandem mass spectrometry. Aldosterone suppression testing is unreliable for anticipating adrenal vein sampling outcomes. The SSST may misinform diagnostic-treatment decisions. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04422756.

Abstract Do Ukrainians still categorically reject political and territorial concessions to Russia as found by Dill et al. (2024a) in July 2022? Or have their attitudes toward resistance changed given mounting costs and uncertain benefits of self-defense against Russia’s aggression? Between December 2024 and January 2025, we presented the original and a modified conjoint experiment with stronger cost treatments to 2,580 Ukrainian citizens, sampled from largely the same locations as before. We find continued categorical resistance to Russian control. Resistance to accepting political neutrality or conceding territory meanwhile has weakened. Ethnic Ukrainians and less war-affected respondents remain comparatively more willing to resist Russia’s aggression than other respondents. Locations’ exposure to war-related violence is not associated with changes in Ukrainians’ attitudes since 2022. Our findings help us better understand how the attitudes of conflict-affected populations evolve over time and shed light on public support for a potential political settlement in Ukraine.

Adjunctive corticosteroids such as dexamethasone are recommended in tuberculous meningitis treatment, despite modest and heterogeneous survival benefit. Leukotriene A4 hydrolase (LTA4H) genotypes associate with distinct intracerebral inflammatory phenotypes and may determine corticosteroid response in tuberculous meningitis, with benefit observed in hyperinflammatory TT genotype but uncertain benefit in lower inflammation CC and CT genotypes. Here, in a phase 3, placebo-controlled trial of human immunodeficiency virus-negative Vietnamese adults with tuberculous meningitis, we randomized 613 LTA4H CC- and CT-genotype participants to 6-8 weeks of dexamethasone or placebo, aiming to show noninferiority of placebo (hazard ratio margin of 0.75) or its superiority. Given the significant survival benefit of dexamethasone previously seen in LTA4H TT-genotype individuals, TT-genotype participants all received open-label dexamethasone and were not randomized. A total of 89 TT-genotype participants received open-label dexamethasone. In CC- and CT-genotype participants, the primary endpoint of all-cause death or new neurological event over 12 months from randomization occurred in 108/305 (35.4%) given dexamethasone and 110/308 (35.7%) given placebo (hazard ratio of 0.99, 96% confidence interval (adjusted for multiple testing) 0.748-1.31). The number of observed primary endpoints (n = 218) exceeded the prespecified number (n = 184) used to calculate the trial's sample size and power. Placebo noninferiority was not established in the CC and CT population or in individual genotype subpopulations. Benefit or heterogeneity of effect was not observed by any prespecified subgroup. In TT-genotype participants, the primary endpoint occurred in 28/89 (31.5%) participants, similar to CC and CT participants. Outcomes were not significantly better in TT-genotype participants versus CC- or CT-genotype participants. In CC- and CT-genotype participants, serious adverse events occurred in 161/305 (52.8%) dexamethasone-treated participants and 160/308 (51.9%) placebo-treated participants. In conclusion, neither noninferiority nor superiority of placebo was established in human immunodeficiency virus-negative LTA4H CC- and CT-genotype adults with tuberculous meningitis, and dexamethasone was safe. The modest and heterogeneous benefit of dexamethasone indicates that greater understanding of tuberculous meningitis pathophysiology is needed, alongside better targeted, more effective anti-inflammatory agents than corticosteroids (ClinicalTrials.gov NCT03100786 ).

SummaryBackgroundPhysical restraints are widely used in intensive care units (ICUs) despite uncertain clinical benefit and risks. We aimed to characterise patterns of restraint use, demographic and clinical predictors, and temporal trends before and after introduction of federal restraint-related reporting requirements.MethodsWe conducted a retrospective cross-sectional study of 51,838 adults admitted to ICUs at Beth Israel Deaconess Medical Center, Boston, MA, USA, between 2008 and 2022, using data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) electronic health record repository. Primary outcome was the proportion of ICU days with documented physical restraint use. Associations between restraint use and demographic and clinical factors were estimated using a binomial generalised linear model with a logit link. Propensity score matching compared Black and White patients under varying adjustment specifications.FindingsAmong 51,838 patients (mean age 63.8 years; 57% male), 21,091 (40.7%) experienced restraint. Use increased from 36.9% in 2008–10 to 44.0% in 2020–22 (p < 0.0001). Asian (aOR 0.84, 95% CI 0.79–0.89) and Hispanic/Latino patients (aOR 0.87, 95% CI 0.83–0.92) had lower odds of restraint than White patients. Propensity score matching between Black and White patients revealed ethnic patterns were highly sensitive to model specification: excluding demographic characteristics revealed significant disparities, which were attenuated when psychiatric diagnoses were also excluded. Matched White patients were not representative of all White ICU patients but rather a subset resembling Black patients on observed characteristics.InterpretationRestraint practices appear to vary with patient acuity, institutional factors, and communication barriers. The sensitivity of ethnic disparities to psychiatric diagnosis adjustment suggests these diagnoses may function as mediators rather than confounders, potentially reflecting systematic differences in clinical assessment along the causal pathway between ethnicity and restraint decisions. The non-representativeness of matched cohorts underscores that disparities depend on which patient subgroups are compared. Prospective multisite studies with standardized assessment protocols are needed to validate findings, disentangle true clinical variation from systematic bias and provide a more comprehensive understanding of restraint practices across US ICU settings.FundingNo study-specific funding was received.