Diabetic wounds represent one of the most severe complications of diabetes, and their clinical management remains challenging. This study investigated the therapeutic potential of adipose-derived stem cell-derived exosomes (ADSCs-Exo) for diabetic wounds. We isolated ADSCs and their exosomes, and by using Transwell and CCK-8 assays, we found that ADSCs-Exo were associated with proliferation and migration of keratinocytes and fibroblasts, and that they also enhanced the angiogenic activity of endothelial cells in vitro. In contrast, these promotive effects were significantly attenuated when exosomes derived from ADSCs with DMBT1 knockdown via siRNA (ADSCssiDMBT1-Exo) were applied. In a diabetic mouse model, ADSCs-Exo treatment significantly accelerated wound healing, whereas the pro-healing capacity of ADSCssiDMBT1-Exo was markedly reduced. To further explore the underlying mechanism, we performed RNA sequencing, which suggested that ADSCs-Exo might exert their therapeutic effects by alleviating ferroptosis and promoting cell proliferation. Subsequent experiments, including TEM, ROS assays, JC-1 staining, and tissue immunofluorescence, provided further support for these mechanistic findings. In summary, this study demonstrates that DMBT1 in ADSCs-Exo participates in alleviating ferroptosis in diabetic wound tissue, which may contribute to creating a favorable microenvironment for cell proliferation and promoting wound healing. This discovery provides a novel potential therapeutic target and strategy for the clinical treatment of diabetic wounds.
Virtual reality (VR) interventions can improve the well-being of persons living with dementia (PLwD). However, little is known about the value of VR interventions on enhancing communication between PLwD and their caregivers in an at-home setting, which was the aim of this study. We also explored whether immersive VR differs from tablet-based technology. Following baseline data collection, PLwD and caregivers completed a 4-week intervention by watching 360-degree videos together, either starting with the VR or Tablet-only condition (2 weeks per device). Seven dyads participated in the study (N = 14). Data of the five dyads who completed the study indicated that both devices facilitated communication, though the extent varied by outcome measure. Both devices had similar influence on observed interactions and reminiscence, but VR led to a higher frequency of conversation initiations compared to the tablet. Together, our results demonstrate the promising application of these technologies for building connections and supporting communication in PLwD and caregivers at home. People living with dementia (PLwD) experience communication declines as their symptoms progress.Communication barriers negatively affect PLwD and caregivers’ relationships, leading them to experience social isolation and poor quality of life.This pilot study reveals that Virtual Reality and tablet-based technologies are both effective tools for facilitating communication between PLwD and their caregivers.
The COVID-19 pandemic compounded unique challenges for adolescents and young adults with cancer (AYAs). Receiving a cancer diagnosis during this period may create further challenges to accessing care, support, and managing stressors. We explored AYAs' experiences of coping with a cancer diagnosis in the context of the pandemic. AYAs (ages 18-39 years) were recruited nationally, completed a brief online survey, and participated in one of six online focus groups from March 2022 to October 2022. We analyzed transcripts using both deductive and inductive coding to identify themes. Ten AYAs received a cancer diagnosis between 2020 and 2021 and participated in focus groups. Participants were all female and non-Hispanic White. Common themes were delays in diagnosis and restricted treatment options, compounded fear of cancer diagnosis and risk of COVID-19, and psychological distress and management of cancer and the pandemic. AYAs also discussed unexpected advantages arising from the pandemic. Isolation, health care protocols that limited family involvement, and the emotional and mental health impacts of the pandemic have created additional challenges for newly diagnosed AYAs to navigate. Our findings have implications for AYAs' health care beyond a pandemic, especially for those who may require physical isolation to manage health risks.
The hypothesis that protein kinase C (PKC) participates in the signaling stage of the cardioprotective response to the administration of probiotics was tested in experiments on male Wistar rats using a model of systemic inflammatory response syndrome (SIRS), which includes obesity and chemically induced colitis. To provide probiotic cardioprotective effects, Lactobacillus acidophilus (LA-5) and Bifidobacterium animalis subsp. lactis (BB-12) were administered orally. PKC inhibitor chelerythrine at a dose of 0.5 mg/kg was administered intraperitoneally 20 min before the start of isolated Langendorff heart perfusion. Global ischemia (30 min) and reperfusion (90 min) were simulated, after which the size of the necrosis zone was histochemically determined. In the SIRS group, we observed a significant increase in leukocyte count and the size of the necrosis zone (by 39%; p < 0.05) in comparison with the control. In groups with probiotic correction and PKC + probiotic, the size of the necrosis zone was significantly lower than in the SIRS group. Administration of chelerythrine did not abolish the cardioprotective effect of probiotics. In the SIRS model, probiotic-induced cardioprotection is mediated by mechanisms that prevent ischemic/reperfusion damage that differ from the PKC pathway.
Large language models (LLMs) have the potential to provide individualized preventive care guidance at scale. Research, however, has found mixed performance among a small set of LLMs queried about select preventive care activities. These findings call for testing a larger set of LLMs on a wider range of preventive care topics. This study aims to assess whether various popular LLMs generate outputs about preventive care consistent with a comprehensive set of recommendations from the US Preventive Services Task Force (USPSTF). We investigated whether 35 popular LLMs produced outputs consistent with all publicly available USPSTF recommendations (n=142) published as of May 2025. The study occurred in 2 waves (wave 1, 2025: 28 LLMs; wave 2, 2026: 10 LLMs; 3 LLMs overlapping across waves). LLMs received queries from simulated users who, in baseline prompts, sought nonbinding, hypothetical advice about whether to participate in particular preventive care activities given their inclusion in a relevant population. LLM raters assessed LLM-USPSTF concordance (interrater reliability, wave 1: κ=0.8893; wave 2: κ=0.9366). Wave 2 tested chain-of-thought, few-shot, and role-based prompts (3 variants each for 426 tests per prompting approach per model). Wave 2 also tested an iterative prompt that sought clarification about previous LLM responses and a prompt that eliminated the user's reference to nonbinding, hypothetical advice. Automated methods classified responses to detect sources of LLM-USPSTF discrepancy. Further tests prompted LLMs to rate preventive care activities for relevant populations using the USPSTF grading scale. Focusing on cases where LLM raters agreed, the study found in its baseline prompts that the LLM with the highest concordance rate generated responses consistent with USPSTF recommendations in 66.92% (89/133) of tests in wave 1 and 87.77% (122/139) of tests in wave 2; the LLM with the lowest rate accorded with USPSTF recommendations in 45.19% (61/135) of tests in wave 1 and in 50.36% (69/137) of tests in wave 2. Eliminating reference to nonbinding, hypothetical advice did not alter the highest-performing model's rate of concordance (122/139, 87.77%). The highest concordance rate increased with chain-of-thought (404/421, 95.96%), role-based (371/416, 89%), and iterative prompting (127/140, 90.71%); however, it moderately decreased with few-shot prompting (361/419, 86.15%). Automated content analysis found high rates of LLMs avoiding definitive recommendations. When prompted to grade preventive care activities, the highest-performing LLM matched USPSTF grades in 85.92% (122/142) of tests in wave 1 and in 94.37% (134/142) of tests in wave 2. LLMs' consistency with USPSTF recommendations varies. Deviations result mainly from LLMs' avoidance of definitive statements. LLM-USPSTF concordance has improved markedly in newer models, and this concordance increases with particular prompting approaches.
Objective: To adapt the Borderline Symptom List 23 (BSL-23) to Brazilian Portuguese and evaluate its psychometric properties in a large nonclinical sample. Methods: A total of 2,682 participants completed an online questionnaire between December 2021 and January 2022. Participants had a mean age of 26.64 years; most were female (78.2%) and had completed higher education. The adaptation process followed established guidelines, including translation, back-translation, expert evaluation, and target-population review. In addition to the BSL-23, participants completed the Depression, Anxiety and Stress Scale-21 Items (DASS-21), Difficulties in Emotion Regulation Scale (DERS), Barratt Impulsiveness Scale, and Childhood Trauma Questionnaire. Statistical analyses included exploratory and confirmatory factor analyses, internal consistency assessment, and tests of concurrent validity and measurement invariance. Results: The BSL-23 maintained a unidimensional structure and demonstrated excellent internal consistency (Cronbach α=0.95). Exploratory factor analysis indicated high factor loadings for most items, while confirmatory factor analysis required minor adjustments due to collinearity between certain item pairs. Measurement invariance analyses showed small but statistically significant gender differences with minimal practical impact. Concurrent validity was supported by strong correlations with DASS-21 stress and depression subscales and moderate correlations with DERS dimensions. Conclusion: The Brazilian Portuguese version of the BSL-23 demonstrated robust psychometric properties, confirming its validity for use in Brazilian samples. Future studies should include clinical populations and assess test-retest reliability to strengthen evidence of temporal stability. Prim Care Companion CNS Disord 2026;28(4):26m04184. Author affiliations are listed at the end of this article.
Polypoidal choroidal vasculopathy (PCV) is a vascular disease of the choroid characterized by polypoidal lesions and a branching vascular network, leading to recurrent exudation and hemorrhage. It is a major cause of visual disability and is particularly prevalent in Asian populations. PCV is similar to neovascular age-related macular degeneration (nAMD) in morphological characteristics but is increasingly recognized as part of the pachychoroid disease spectrum, although consensus has yet to be reached. Despite overlapping features with nAMD, PCV demonstrates distinct pathophysiology and treatment response, necessitating accurate differentiation for management optimization. Diagnosis relies on multimodal imaging, with indocyanine green angiography (ICGA) as the gold standard, supported by optical coherence tomography (OCT) and OCT angiography. Anti-vascular endothelial growth factor (VEGF) therapy is the mainstay of treatment; however, responses are heterogeneous and are often suboptimal or incomplete. Long-term outcomes are frequently influenced by complications such as hemorrhage, fibrosis, and atrophy, highlighting the need for durable disease control. Advances in imaging and a better understanding of pachychoroid biology are enabling more personalized, activity-guided treatment strategies, with the potential to improve long-term outcomes and reduce treatment burden. In this vodcast, Professor Junyeop Lee discusses the key clinical and pathological features of PCV, how it differs from nAMD, and why it remains challenging to diagnose and manage. The discussion also explores evolving diagnostic approaches, current treatment strategies, and emerging directions in PCV care. Vodcast available for this article. Supplementary file1 (MP4 279147 KB).
Two percent to 50% of patients undergoing elective cardiac surgery experience acute kidney injury (AKI) postoperatively. Medications to prevent AKI after elective cardiac surgery have not been identified. In patients undergoing elective cardiac surgery, to evaluate whether initiating dapagliflozin 1 day prior to surgery reduces the incidence of AKI at 7 days after cardiac surgery, compared with placebo. Multicenter, double-blind, placebo-controlled randomized clinical trial conducted at 2 academic medical centers and 5 nonacademic hospitals in the Netherlands. Eligible participants were adults undergoing elective cardiac surgery. Enrollment occurred between June 8, 2023, and January 27, 2025. Final follow-up occurred May 16, 2025. Patients were randomized 1:1 to receive either dapagliflozin (10 mg orally; n = 392) or placebo once daily (n = 392), beginning on the day before surgery and continuing through the second postoperative day (total of 4 doses). The primary outcome was the between-group difference in AKI (defined as an increase in serum creatinine level by at least 0.3 mg/dL [26.5 µmol/L] within 48 hours after surgery, a 1.5-fold creatinine increase within 7 days of surgery, or urine output less than 0.5 mL/kg/h for 6 to 12 hours according to Kidney Disease: Improving Global Outcomes criteria) during the first 7 postoperative days. Of 784 participants enrolled, 778 (99%) completed follow-up testing (median age, 68 [61-74] years; 76% male; 97% White; median body mass index, 27 [IQR, 25-30]; and median estimated glomerular filtration rate, 80 [IQR, 67-89] mL/min/1.73 m2). Compared with placebo, dapagliflozin reduced the incidence of AKI (28% vs 52%; relative risk, 0.54 [95% CI, 0.45-0.65]; P < .001) over 7-day follow-up after surgery. Atrial fibrillation and reoperation were the most frequent adverse events. The incidence of atrial fibrillation was 45% (176/392) in the dapagliflozin group vs 45% (176/392) in the placebo group, and the incidence of reoperation was 11% (43/392) vs 10% (39/392), respectively. In patients undergoing elective cardiac surgery, 4 doses of dapagliflozin, beginning the day before surgery, reduced the incidence of AKI during the 7-day postoperative period. ClinicalTrials.gov Identifier: NCT05590143.
Smoking relapse is prevalent, yet its long-term association with incident asthma remains underexplored. Repeated quit-relapse cycles may exacerbate airway inflammation more acutely than steady-state smoking. We investigated the association between smoking-relapse trajectories and incident asthma risk using a nationally representative longitudinal dataset. We analyzed 10-year data (2009-2018) from the Korea Health Panel Survey for 16,240 adults without baseline asthma. Participants were classified into five trajectories: non-smokers (NS), successful quitters without relapse (SQ-), successful quitters with relapse (SQ+), unsuccessful quitters with relapse (UQ+, chronic relapsers), and always smokers (AS). Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for incident asthma (ICD-10 J45-J46). During the 10-year follow-up, 159 incident asthma cases were identified. Compared to NS, chronic relapsers (UQ+) exhibited the highest risk (aHR 3.81; 95% CI 1.84-7.91), followed by SQ- (aHR 2.54; 95% CI 1.30-4.96) and AS (aHR 2.25; 1.08-4.71). While UQ + showed a higher point estimate than AS, the difference was not statistically significant. Other significant risk factors included age ≤65 years, Medical Aid enrollment, and higher comorbidity scores. Smoking-relapse trajectories, particularly chronic relapse, are associated with an elevated risk of incident asthma. These findings should be interpreted as hypothesis-generating and require confirmation in independent cohorts.
Machine learning models for Obstructive Sleep Apnea (OSA) diagnosis have largely inherited some structural limitations: reliance on generic, opportunistically collected feature sets; use of the Apnea-Hypopnea Index (AHI) as the sole ground truth; poor performance in multi-class severity grading; and predictions that offer clinicians no mechanistic insight. This study addresses these gaps by prospectively assembling a multi-domain dataset that, alongside established demographic, anthropometric, and questionnaire-based predictors, incorporates a panel of craniofacial and intraoral metrics specifically designed to capture the structural-anatomical contributors to OSA - integrating these into an interpretable framework for three-class severity classification evaluated against both AHI and the Oxygen Desaturation Index (ODI). In this single-center study, 233 treatment-naïve adults from a tertiary referral cohort (61.8% severe OSA prevalence) underwent in-laboratory polysomnography (PSG). All predictor variables were collected prior to PSG outcome disclosure through a standardized clinical examination, requiring no overnight recording or specialized equipment. An Artificial Neural Network (ANN) was independently trained for three-class severity classification (No/Mild, Moderate, Severe) for each index. Model performance was evaluated on an independent test set (n = 47; 20% of the sample), with interpretability assessed using SHapley Additive exPlanations (SHAP). Comparison with an anatomy-excluded ablation model was conducted to establish the added value of the full feature set. The AHI-based model achieved 87.2% overall accuracy (sensitivity/specificity: No/Mild 0.93/0.97, Moderate 0.80/0.91, Severe 0.88/0.93). The ODI-based model achieved 76.6% accuracy, offering reliable exclusion of severe desaturation burden (No/Mild specificity: 0.94). Univariate analyses confirmed significant associations between OSA severity and STOP-BANG score, age, BMI, neck circumference, observed apnea, loud snoring, high blood pressure, Cervico-Mental Angle, Mentocervical Distance, and submental fat (all p ≤ .034 for both indices). SHAP analysis further identified V-shaped maxillary arch, Mallampati score, increased overjet, and alcohol use as influential model predictors - several reaching high model rankings despite modest univariate significance. Notably, AHI and ODI models diverged in their feature weighting - anatomy-driven features dominated AHI prediction while body habitus and comorbidity markers dominated ODI. Against a conventional demographic and questionnaire-based ablation model, the full anatomy-inclusive ANN achieved substantially higher accuracy (87.2% vs. 72.3%), with the largest gain at the Moderate-class boundary (sensitivity: 0.80 vs. 0.58). As a proof-of-concept, this study demonstrates that an interpretable ML framework integrating craniofacial and intraoral assessments with standard clinical predictors can classify OSA severity across three classes and provide feature-level explanations to support clinical reasoning. By developing parallel AHI and ODI models, the framework moves beyond AHI-only paradigms, though both remain frequency-based surrogates; hypoxic burden - quantifying the cumulative oxygen desaturation load per sleep period - is the more physiologically complete target toward which this line of work should progress. Findings are limited by single-center design, spectrum bias from a tertiary referral cohort, modest sample size, and absence of inter-rater reliability data. External validation in larger, more representative populations is needed to confirm the robustness and clinical utility of this approach.
Background: International fieldwork placements (IFPs) may cultivate personal and professional competencies within healthcare education. Limited research explores how IFPs shape the development of Canadian occupational therapists in the early stages of their careers. Purpose: To explore how Canadian occupational therapists make sense of their IFP experience in relation to their transition from student to practitioner and their current professional practice. Method: Data were collected through semi-structured individual interviews which sought to encourage reflection and dialogue about participants' IFP experiences, post-graduation transitions, and lasting impacts. Interpretative phenomenological analysis (IPA) was used to co-construct meaning from participants' narratives and identify convergent and divergent experiences. Findings: Eight participants completed IFPs in partnership with low-income countries; one completed the placement virtually. Four key themes were identified: Self-Efficacy, Resourcefulness, Relational Growth, and Cultural Responsiveness. These themes reflect participants' engagement with complex intercultural contexts, personal and professional growth, and critical reflection on their evolving identities as occupational therapists. Conclusion: Our study provides insight into how IFPs influence occupational therapists, particularly in shaping professional identity and informing culturally responsive practices. Findings highlight the value of IFPs in occupational therapy education and may inform curriculum design, student selection, and strategies to improve accessibility.
Targeted cancer therapies increasingly require platforms that can penetrate poorly perfused tumor regions while minimizing systemic toxicity. Bacteria, owing to their intrinsic tumor tropism, genetic programmability, and immunostimulatory properties, have re-emerged as versatile anticancer agents, ranging from attenuated tumor-colonizing strains to highly engineered "living therapeutics." In this review, we synthesize the mechanistic foundations and therapeutic advances of bacterial-based cancer therapy through four major themes. First, we examine foundational mechanisms, including tumor-selective colonization, direct oncolysis and cytotoxicity, activation of innate and adaptive immunity, and remodeling of the tumor microenvironment. Second, we discuss engineering strategies that enable controllable delivery of therapeutic payloads, such as cytokines, antibodies and nanobodies, enzyme-prodrug systems, toxins, and nucleic-acid therapeutics, while also improving biosafety and biocontainment. Third, we evaluate combination strategies integrating bacteria with chemotherapy, radiotherapy, phototherapy, and immunotherapy, with emphasis on how bacteria complement conventional modalities by targeting hypoxic, necrotic, and immunologically refractory tumor niches. Fourth, we summarize translational progress, including representative early-phase clinical experiences, manufacturing challenges, and major safety constraints. We also highlight emerging microbiome-disease databases and computational resources that may support target selection, biomarker discovery, and therapy-response stratification. Current evidence supports bacteria as a promising precision modality, particularly for immunologically "cold" or hypoxic tumors; however, major challenges remain in the predictability of intratumoral distribution, host clearance, genetic stability, and long-term safety. Addressing these barriers through rigorous engineering, standardized manufacturing, and clinically meaningful endpoints will be essential for the next generation of bacterial therapeutics in oncology.
Digital applications based on health care conversational agents (HCAs) are increasingly being developed to support health care provision. The usability and user experience of these solutions are critical determinants of their acceptability and, consequently, their impact on health-related outcomes. This systematic review aims to synthesize current evidence on the use of valid and reliable subjective instruments for assessing the usability and user experience of HCAs and to examine whether assessment outcomes vary according to their technical characteristics. A systematic search was conducted in PubMed, Web of Science, and Scopus from inception to February 2026. Studies were included if they used subjective instruments to evaluate the usability or user experience of HCAs. A total of 127 studies met the inclusion criteria. The studies examined 3 categories of HCAs-text-based, voice-based, and embodied-applied to patient care, health education and prevention, health data collection, and support for daily activities among older adults. The System Usability Scale (SUS) was the most frequently used assessment instrument. Comparative analysis of SUS scores indicated higher usability ratings for text-based HCAs relative to voice-based and embodied systems. However, SUS and other subjective instruments used in the included studies may not fully capture key dimensions of usability and user experience of HCAs. Additionally, substantial heterogeneity was observed in assessment methodologies across studies. Comparative analysis suggested that text-based HCAs were associated with significantly higher SUS scores than voice-based and embodied HCAs. However, this finding should be interpreted with caution given the substantial heterogeneity across the included studies in health care application domains, study designs, evaluation contexts, participant populations, and HCAs' implementation and use characteristics, as well as the limitations of the SUS in evaluating the usability of modern HCAs. The variability in assessment approaches underscores the need for standardized protocols and the development of more context-specific evaluation frameworks to enhance methodological consistency and comparability across studies.
Pathogenic variants in BRCA1 and BRCA2 confer substantial risks of breast and ovarian cancer; however, risk for female individuals undergoing testing, particularly those with variants of uncertain significance (VUS) or negative results, remain poorly defined. To estimate lifetime incidence of breast and ovarian cancer among female individuals undergoing BRCA1 or BRCA2 testing across all result categories and evaluate the modifying association of family history. This retrospective cohort study was conducted as part of the What Comes Next Cohort Study, a near-population-based cohort in Ontario, Canada, established through linkage with administrative databases. Female participants who underwent BRCA1 or BRCA2 testing from 2007 to 2016 were matched 1:5 to females from the general population. Participants were followed up to September 2024. Data were analyzed from May to December 2025. The outcome of interest was the cumulative incidence of breast and ovarian cancer to age 80 years, stratified by genetic test result and family history. Of 15 986 individuals in the What Comes Next Cohort Study cohort, 6966 individuals eligible for breast cancer analyses (median [IQR] age, 49 [38-60] years) were matched to 34 830 individuals from the general population and 13 276 individuals eligible for ovarian cancer analyses (median [IQR] age, 51 [41-61] years) were matched to 66 380 individuals from the general population. Cumulative breast cancer incidence to age 80 years was 62.1% (95% CI, 52.2%-69.9%) for BRCA1 pathogenic variant carriers and 66.1% (95% CI, 57.5%-72.9%) for BRCA2 pathogenic variant carriers, compared with 12.0% (95% CI, 11.2%-12.8%) in the general population; corresponding ovarian cancer incidence was 56.0% (95% CI, 40.0%-67.7%) for BRCA1 pathogenic variant carriers and 29.3% (95% CI, 14.2%-41.7%) for BRCA2 pathogenic variant carriers, compared with 1.5% (95% CI, 1.3%-1.7%) in the general population. Family history modified breast cancer risk, reaching a cumulative incidence of 86.3% (95% CI, 70.9%-93.5%) in carriers with at least 2 affected first-degree relatives vs 55.8% (95% CI, 45.4%-64.2%) in carriers without a family history of breast cancer. Among individuals with test results positive for pathogenic variants, lifetime risk of ovarian cancer was similarly modified by family history, reaching 64.2% (95% CI, 37.0%-79.7%) in those with vs 38.2% (95% CI, 25.8%-48.4%) in those without a family history of ovarian cancer. Individuals with VUS and negative test results also had increased lifetime breast cancer risks (31.2% [95% CI, 19.2%-41.4%] and 26.3% [95% CI, 23.0%-29.4%], respectively) but no increase in ovarian cancer risk. Individuals with test results negative for a known familial variant had risks similar to the general population. In this cohort study of females who underwent BRCA1 or BRCA2 testing, the lifetime cancer risk varied substantially across BRCA test result groups and was further modified by family history. Elevated breast cancer risk among individuals with VUS or negative results highlights the need for individualized risk assessment and management beyond genetic test results alone.
Moral distress can occur when clinicians cannot provide clinically appropriate care due to external constraints. In the wake of Dobbs v Jackson Women's Health Organization, moral distress has been reported among subsets of obstetrician-gynecologists (OB-GYNs), yet little is known about how moral distress manifests among OB-GYNs nationally. To evaluate the extent to which OB-GYNs in a nonprobability national sample experienced specific clinical constraints around abortion-related care and the extent to which these constraints were associated with moral distress overall and within policy environments. This cross-sectional study used a national online survey of US OB-GYNs conducted in mid-2025. Attending OB-GYNs practicing in the US, providing care to pregnant patients, and either general OB-GYNs or subspecialists in maternal-fetal medicine or complex family planning were recruited by a physician market research firm. Experience of clinical constraints associated with state abortion laws, including associations with patient counseling, ability to provide care, and ability to provide care for a patient with a potentially life-threatening pregnancy complication. State abortion policy climate was dichotomized into restrictive (29 states) and protective (21 states and the District of Columbia). General moral distress (Moral Distress Appraisal scale; score range, 0-5; higher scores indicate greater moral distress). Among 864 OB-GYNs surveyed (483 female [56.0%]; 623 aged ≥45 years [72.1%]; 113 Asian [13.1%], 35 Black [4.1%], and 625 White [72.3%]; 54 Hispanic [6.3%]), 795 respondents (92.0%) were nonsubspecialists. Self-reported endorsement of each clinical constraint was higher in abortion-restrictive than protective states (eg, counseling constraints: 405 of 566 participants [71.6%] vs 86 of 298 participants [28.9%]; P < .001). Associations were observed between all clinical constraints and moral distress scores (greater endorsement associated with increased overall moral distress). For example, when asked whether their state's abortion laws constrained their ability to provide care for patients with potentially life-threatening pregnancy complications, participants who endorsed this somewhat had an effect estimate (standard error [SE]) of 0.29 (0.07) for increased moral distress score (P < .001), while those who very much endorsed this had an effect estimate (SE) of 0.78 (0.10) for increased score (P < .001) compared with those who endorsed this not at all. Magnitude, direction, and significance of associations were similar in abortion-restrictive and abortion-protective states. In this study, although self-reported experience of abortion-related clinical constraints was higher in abortion-restrictive vs abortion-protective states, experience of constraints was associated with moral distress across policy contexts. These findings suggest that institution-level programs and policies to reduce moral distress and its determinants among OB-GYNs may be indicated nationally.
Objective: Internet gaming disorder (IGD) has gained increasing global recognition, yet little is known about how health care providers perceive and manage this condition in clinical practice. The objective of this study was to assess health care providers' IGD-related beliefs, familiarity with diagnostic criteria, confidence in diagnosis and management, and perceived training needs. Methods:A cross-sectional online survey of internal medicine and psychiatry health care providers was conducted between September and October 2025 at a large academic medical center, assessing IGD-related beliefs, familiarity with diagnostic criteria, confidence in diagnosis and management, and perceived training needs. Results: Among 67 respondents, most participants endorsed IGD as a clinically significant condition (84%) that contributes to psychiatric comorbidities (87%). However, fewer than half of providers reported confidence diagnosing (44%) or managing IGD (29%), and only 37% were familiar with currently proposed Diagnostic and Statistical Manual of Mental Disorders criteria. Psychiatric health care providers reported greater confidence and familiarity with IGD than their internal medicine counterparts, particularly in diagnosis, management, and identification of diagnostic criteria during clinical encounters. Overall, 81% of participants indicated that they would benefit from additional IGD-related education. Conclusion: Despite broad recognition of IGD's clinical significance, substantial gaps remain in provider confidence and familiarity with diagnostic and management approaches, particularly outside of psychiatry. These findings identify actionable gaps in provider preparedness and highlight the need for targeted educational efforts to support effective clinical management of IGD across medical specialties. Prim Care Companion CNS Disord 2026;28(4):26m04192. Author affiliations are listed at the end of this article.
Daratumumab-based triplet and quadruplet regimens have significantly improved patient outcomes as first-line (1L) treatment in newly diagnosed multiple myeloma (MM). However, with the evolution of available 1L combination regimens, the proportion of patients with exposure and refractoriness to multiple treatment classes at first relapse is increasing. Patients experience worsening prognosis with each successive relapse, and attrition rates increase with each line of therapy (LOT). Therefore, in the second-line setting and beyond (2L+), it is critical to use the most effective treatment available up front to optimize patient outcomes. Treatments that target the B-cell maturation antigen (BCMA), particularly chimeric antigen receptor T-cell therapy, are rapidly becoming a new 2L+ standard of care (SOC). Other BCMA-targeted options, including combinations of belantamab mafodotin plus dexamethasone with bortezomib or pomalidomide, have shown promising efficacy in the 2L+ setting. BCMA-targeted bispecific antibodies are a new treatment option being explored in earlier LOTs and offer patients a steroid-sparing approach with the potential for use across all practice settings. Teclistamab combined with daratumumab is approved in the United States for patients with ≥ 1 prior LOT based on results of the phase 3 MajesTEC-3 trial, in which teclistamab-daratumumab significantly improved progression-free and overall survival versus SOC in patients with 1 to 3 prior LOTs. Several other clinical trials of BCMA-targeted bispecific antibodies in earlier LOTs are ongoing, including teclistamab monotherapy (MajesTEC-9), teclistamab combined with the G protein-coupled receptor class C group 5 member D (GPRC5D)-targeted bispecific antibody talquetamab (MonumenTAL-6), elranatamab (MagnetisMM-5), and linvoseltamab (LINKER-MM3), paving the way for the next evolution of treatment options for patients following first relapse. In this podcast, 2 leading hematologists discuss the unmet needs in 2L+ MM, considerations for treatment decisions, and the evolving treatment landscape with a focus on BCMA-targeted bispecific antibodies, a rapidly advancing class of treatments in this setting. Podcast (MP4 179036 KB).
The global surge of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (E. coli) imposes an unnoticed but significant threat, fueling antimicrobial resistance (AMR). Being a neglected host, camels suffering from subclinical mastitis (SCM) caused by ESBL-producing E. coli present a crucial one-health hazard. The current study investigated the prevalence, associated risk factors, in silico structural modeling, and antimicrobial resistance profiling of ESBL-producing E. coli strains isolated from SCM in camels. A total of 384 milk samples were evaluated by the California mastitis test (CMT), followed by phenotypic and genotypic approaches to identify and isolate E. coli and ESBL-producing E. coli. The results revealed 35.1% and 37.8% prevalence of SCM and E. coli, respectively. The potential risk factors, like breed, use of teat dip, stage of lactation, herd hygiene, and parity, were significantly associated with SCM in camels. Molecular insights determined 33.4% prevalence of ESBL-producing E. coli isolates encoded by the blaCTX-M gene. Phylogenetic analysis of the blaCTX-M gene of study E. coli isolates (PX238420, PX238421, PX238422, and PX238423) revealed close genetic resemblance with retrieved NCBI sequences from different countries. In silico protein analysis revealed the structural configurations of the protein driving AMR. Moreover, Antimicrobial resistance profiling of study isolates revealed a high resistance pattern among beta-lactam antibiotics. The study highlights increasing prevalence and associated AMR of ESBL-producing E. coli isolates in camel SCM and suggests devising better management practices and an antimicrobial stewardship program to reduce the associated losses.
Clinical tolerability refers to the degree to which patients can endure side effects without discontinuing treatment. Despite its frequent inclusion alongside efficacy and safety, tolerability in clinical trial publications is typically reported without a clear description of the methods used to assess it. We examined how treatment tolerability is evaluated in clinical trial publications. A targeted review of PubMed was conducted for publications of phase I, II, or III clinical trials published in 2024 and including tolerability in the title. Methods used to assess tolerability were extracted along with claims related to treatment tolerability. Of 339 identified publications, 154 met the inclusion criteria. Tolerability was referenced in the study objective or conclusion in ~95% of publications; fewer than half (n = 72 [46.8%]) reported these methods specifically in the methods section, and 38 (24.7%) reported tolerability findings. Over 85% of included studies implicitly or explicitly equated tolerability with safety. Clinical outcome assessments for tolerability were included in 22 trials (14.3%), with six incorporating preexisting clinical outcome assessment tools. Tolerability was predominantly described favorably, e.g., 'well tolerated' (n = 126 [85.7%]) or 'tolerable' (n = 17 [11.6%]). This review highlights opportunities to improve the scientific utility of tolerability data in clinical trial publications. Methods for assessing tolerability are often inconsistently described in publications and the terms safety and tolerability are frequently used interchangeably, which can obscure important distinctions. Future research should focus on developing methodological guidance and promoting clinical trial standards that clearly define how tolerability is assessed. Such advances will strengthen regulatory decision making, support clinical practice, and ultimately enhance patient care.
Mental chronometry tasks commonly presume that real-time action imagery indicates high action imagery ability (AIA). However, factors that systematically influence imagery durations undermine the validity of AIA scores based on deviations from real-time action imagery. Therefore, we introduce and validate a novel approach for measuring AIA using mental chronometry. This approach relies on the relationship between a movement's difficulty and its duration (Fitts' law), with AIA scores quantifying the degree to which this relationship is preserved in action imagery. In a Chronometric Radial Fitts' Task (CRFT), participants (N = 30) executed and imagined both tapping (with a stylus) and clicking (with a computer mouse) radially arranged targets. Single execution and imagery durations were isolated through simultaneous space bar presses. Targets varied in difficulty according to Fitts' law, which held across all four conditions (for both tools, when executing and imagining the movements). The AIA scores derived from the proposed Fitts' law approach outperformed those derived from earlier mental chronometry approaches, being the only scores indicating convergent validity across tools. Using the stylus, larger absolute and relative deviations from real-time action imagery were consistently associated with higher subjective AIA, reinforcing validity concerns. Participants struggled to incorporate the computer mouse's properties into the internal model of the movement, resulting in imagery with the computer mouse relying on internal models similar to the stylus (simpler tool). In addition to offering a refined approach for measuring manipulation- and timing-related AIA, our study highlights the importance of tool familiarity in mental chronometry.