Family medicine (FM) and emergency medicine (EM) have Accreditation Council for Graduate Medical Education-mandated point-of-care ultrasound (POCUS) training. While POCUS has many uses in internal medicine (IM), lack of mandated training has resulted in wide variation and lack of standardization in graduate medical education (GME) curricula. To perform a narrative review asking the questions: what are the recommended POCUS curriculum elements across FM, EM, and IM, and how can these inform the development of a more standardized curriculum? This narrative review was conducted in March 2024. Authors searched published materials from the following organizations: Canadian Association of Emergency Physicians, American College of Emergency Physicians, College of Family Physicians of Canada, American Academy of Family Physicians, Canadian Society of Internal Medicine, Society of Hospital Medicine, Society of General Internal Medicine, Alliance for Academic Internal Medicine, and American College of Physicians. Only documents endorsed for POCUS training/education were included. Narrative review was chosen due to the small number and large heterogeneity of documents. All documents were reviewed, and common themes were identified by the authors of the study; they were later compared using a large language model, and authors verified by repeat analysis. Nine documents, 2 online courses, and 5 procedural position statements were identified and reviewed. Both authors agreed on the final themes: POCUS uses, basic knowledge and teaching methods for POCUS, image number requirements and competency assessment, and quality control. There is overlap between recommended curricula for POCUS in major organizations. Internal medicine does not have an apparent defined, standardized curriculum for GME.
Patient-reported outcome measures (PROMs) are important tools for assessing the impact of skin diseases on health-related quality of life (HRQoL). However, comparative data on the measurement properties of commonly used instruments are limited. The objective of this study was to compare the measurement properties of the Dermatology Life Quality Index (DLQI), DLQI-Relevant (DLQI-R), and Skindex-29 in a cohort of patients with chronic skin disease. Participants completed the DLQI, Skindex-29, and Patient-Reported Outcomes Measurement Information System (PROMIS) measures at baseline and 3 months. Structural validity was assessed with confirmatory factor analysis; internal consistency with Cronbach's alpha; construct validity via known-groups comparisons and PROMIS correlations; informativity with Shannon's index; and responsiveness with standardized response means, Cohen's d, and change score correlations. Of 549 participants (mean age 37.8 years; 52.3% female), 406 (74.0%) completed follow-up. All instruments demonstrated high internal consistency (α ≥ 0.85) and no floor or ceiling effects. Skindex-29 domains demonstrated stronger structural validity and informativity compared to DLQI and DLQI-R. Construct validity was supported by expected associations with patient global assessment (PtGA) and PROMIS correlations. The DLQI, DLQI-R, and Skindex Symptoms and Emotions showed moderate responsiveness. The DLQI, DLRI-R and Skindex-29 demonstrated strong measurement properties in a heterogeneous cohort of individuals with chronic skin disease. Skindex-29 showed stronger structural validity and informativity, while the DLQI and DLQI-R demonstrated slightly greater responsiveness. Selection of PROM should depend on the intended clinical or research purpose. Chronic skin conditions, such as acne, eczema, psoriasis, and hidradenitis suppurativa, can affect many areas of daily life, including symptoms, emotional wellbeing, and social interactions. Physicians and researchers often use questionnaires, called patient-reported outcome measures, to better understand this impact from the patient’s perspective. Two of the most widely used in dermatology are the Dermatology Life Quality Index (DLQI), and the Skindex-29. A newer scoring approach to the DLQI, known as the DLQI-Relevant (DLQI-R), was developed to improve accuracy by adjusting how responses are scored when patients indicate that certain questions do not apply to them. In this study, we wanted to understand which of these questionnaires works best in people living with chronic skin conditions. We surveyed over 500 adults in the United States who reported having one or more skin condition. The participants completed the DLQI and the Skindex-29 at the start of the study, and again 3 months later. We found that the Skindex-29 provided a broader and more detailed picture of how skin conditions affect health-related quality of life. The DLQI and DLQI-R, on the other hand, were slightly better at detecting changes in health-related quality of life over time, although the differences between the questionnaires were small. These results show that no single instrument is best for all situations. The choice of questionnaire should depend on the purpose—whether the goal is to capture the full burden of disease, or to measure how much a patient improves with treatment.
Contrast-enhanced volume interpolated breath-hold examination (VIBE) is commonly used for evaluating internal auditory canal (IAC) pathology. Deep learning (DL)-reconstruction has been shown to reduce scan time while maintaining diagnostic quality. Our purpose was to compare the image quality of a DL-reconstructed post-contrast-enhanced VIBE sequence with standard 3D VIBE in a clinical setting. This study included 74 patients undergoing contrast-enhanced MRI for the assessment of IAC pathology. The participants were scanned with a standard 3D VIBE sequence and DL-reconstructed VIBE (DL-VIBE) sequences. Two neuroradiologists performed a head-to-head evaluation of both sequences in terms of image-quality metrics, identification of key anatomic structures, and pathologic enhancement when present. A third neuroradiologist adjudicated the discrepant results. Superiority testing was performed to compare DL-VIBE with standard VIBE in image quality metrics, and a noninferiority test with a 15% margin was performed to test the visibility of key anatomic structures and pathologic enhancing lesions. Interrater agreement and quantitative assessment of an image-wise SNR, contrast-noise ratio, IAC-specific SNR, and tumor volumetric measurements as applicable were performed. DL-VIBE enabled approximately 25% scan time reduction (from 3 minutes 2 seconds on the standard sequence to 2 minutes 17 seconds on the DL sequence). DL-VIBE was superior to standard VIBE for all image-quality metrics (P < .01). DL-VIBE was noninferior to standard VIBE for structural visibility of key structures (P < .001) and was noninferior for pooled pathologic enhancement (P = .049). Interrater agreements were moderate to almost perfect across all categories (κ = 0.515-1). DL-VIBE provided significantly higher mean image-wise SNR (71.8 [SD, 23.2] versus 39.4 [SD, 10.7], respectively; P < .001), while providing comparable lesion conspicuity and volumetric assessment. DL-VIBE is a strong alternative to standard 3D VIBE for clinical IAC assessment, providing superior image quality and comparable visibility of key anatomic structures and enhancing pathology while offering higher image SNR with 25% reduced scan time.
Cardiovascular-kidney-metabolic (CKM) syndrome has emerged as a major global health burden and driver of cardiovascular disease (CVD), the leading cause of death worldwide. Effective management of CKM depends on timely identification of underlying risk factors. Nevertheless, participation rates in primary care-based screenings are low. Consequently, CKM syndrome oftentimes remains undetected until organ damage is clinically present. Community pharmacies offer an accessible, yet underused, setting to enhance early detection. APOSCREEN-1 evaluates the feasibility and diagnostic yield of a pharmacy-based multi-parametric screening for cardiovascular-kidney-metabolic health. APOSCREEN-1 is a prospective single-arm clinical trial conducted in 20 community pharmacies in the German state of Schleswig-Holstein. Adults (n = 1000) aged ≥ 40 years with predefined risk criteria are included. Participants undergo standardized point-of-care testing (glycated hemoglobin, lipid profile, urinary albumin, blood pressure). Additionally, clinical history is assessed and results are transmitted to the study center via an online platform. Patients meeting pre-defined thresholds of the tested parameters are followed up by confirmatory laboratory testing at the study center or at the participants' general practitioner. Primary outcomes include completion rate, implementation metrics from the pharmacy perspective, and the number needed to screen to detect unknown or insufficiently managed cardiometabolic risk factors. Secondary outcomes comprise participant metrics, diagnostic metrics of the screening, evaluation of the clinical impact. This study aims to address the unmet need for scalable prevention of CVD by identification of CKM syndrome risk factors outside traditional primary care settings. Evidence on feasibility, acceptance, and diagnostic benefit may support the use of community pharmacies as an additional access point for early CKM syndrome detection. Future interventional studies will be required to evaluate structured follow-up pathways and long-term effectiveness. This study was registered with the German trial registry (Deutsches Register klinischer Studien) on 29.01.2026, under trial number DRKS00039149.
Inflammatory rheumatic diseases (IRDs) present substantial risks of infection-related comorbidities during pregnancy. This study evaluates the knowledge, experience, and perceptions of healthcare professionals concerning the prevention of these risks. An international, cross-sectional survey was administered using the SurveyMonkey platform. The survey was disseminated to healthcare professionals specializing in rheumatology, obstetrics, infectious diseases, internal medicine, general practice, and related disciplines through social media channels. Developed in accordance with European Alliance of Associations for Rheumatology (EULAR) recommendations, this survey comprised 30 questions, including multiple-choice, Likert-type, and open-ended formats. A total of 201 healthcare professionals from thirty-six countries participated in the study, with rheumatologists comprising the majority (n = 145, 72.1%). Systemic lupus erythematosus (n = 183), systemic vasculitis (n = 141), and rheumatoid arthritis (n = 86) were identified as the diseases associated with the highest risk of infection-related comorbidities. The most frequently recommended infectious conditions for screening included Hepatitis B (n = 142), urinary tract infections (n = 141), and Hepatitis C (n = 129). The primary risk factors were uncontrolled disease activity (n = 176), high-dose corticosteroid use (n = 164), and high disease severity (n = 162). The most significant systemic barriers were insufficient number of specialists (n = 156), and absence of multidisciplinary teams (n = 155). This study identifies structural and educational deficiencies in the management of infection-related comorbidities among pregnant patients with IRD. The results underscore the need for targeted clinical guidelines, enhanced multidisciplinary care models, and expanded pre-pregnancy counseling.
Point-of-care ultrasound (PoCUS) is increasingly integrated into acute care for its diagnostic efficiency and accessibility. While prior studies associate PoCUS use with higher patient satisfaction, little is known about how patients themselves experience it as part of their care. To explore how patients experience PoCUS during acute care encounters and how it shapes their overall perception of care. Qualitative study using semi-structured interviews and reflexive thematic analysis within a constructivist paradigm. Eighteen adult patients who underwent PoCUS during emergency department or inpatient general internal medicine assessments at a tertiary care academic hospital in Ottawa, Canada. Participants were recruited and interviewed at the bedside shortly after receiving PoCUS examinations. Transcripts were inductively coded and analyzed using Braun and Clarke's six-phase framework for reflexive thematic analysis. Three interrelated themes captured how patients experienced PoCUS. First, PoCUS enhanced both emotional reassurance and physical convenience through real-time feedback and avoidance of transport to diagnostic areas. Second, patients perceived PoCUS as integrated within holistic, patient-centered care, where their impressions of PoCUS were intertwined with their impressions of the care they received overall. Third, patients' largely positive experiences were grounded in trust in their physicians despite and in the midst of limited technical understanding of PoCUS. Overall, patients had positive experience with PoCUS integration. With little technical knowledge of PoCUS, patients' positive views were shaped by trust and interaction with physicians. While supporting existing literature, our findings stress the need for clear communication and scope awareness. As PoCUS use increases in prevalence, it should be seen as both a diagnostic tool and a contributor to patient-centered care.
The American Board of Internal Medicine (ABIM) Pilot Pathway E introduces a competency-based certification model designed for international medical graduates (IMGs) who have completed prior internal medicine training outside the USA. Amid persistent physician workforce shortages and growing reliance on IMGs within internal medicine, innovative certification pathways are increasingly necessary. National Match data demonstrate both the substantial contribution of IMGs to internal medicine and the large pool of highly trained physicians navigating prolonged or duplicative training routes. Pilot Pathway E allows eligible IMGs, those who have completed at least 3 years of internal medicine training abroad and an ACGME-accredited ABIM subspecialty fellowship, to pursue eligibility for the Internal Medicine Certification Examination without repeating full US residency training. Competency is validated through accredited fellowship oversight and standardized clinical competence evaluations prior to examination approval. ABIM Pilot Pathway E establishes a 5-year pilot program integrating prior international internal medicine training with performance in US ACGME-accredited subspecialty fellowships. Drawing on lessons from alternative certification models in other specialties, this pathway reflects a broader shift from time-based requirements toward outcomes-based assessment. While implementation considerations include licensure, visa policy, and longitudinal outcome monitoring, Pathway E represents a structured effort to align global physician training with US certification standards while preserving rigor, safety, and educational quality.
Patients on low-dose prednisolone may develop adrenal insufficiency causing reduced health-related quality of life (HRQoL) and increased risk of adrenal crisis. This study examines whether supplemental hydrocortisone during mild to moderate stress improves HRQoL in patients with polymyalgia rheumatica/giant cell arteritis (PMR/GCA) with adrenal insufficiency on low-dose prednisolone. A multicentre, randomised, double-blinded, placebo-controlled, clinical trial including patients with PMR/GCA receiving ongoing prednisolone ≤5 mg/day. Eligible patients undergo an adrenocorticotropic hormone (ACTH) test, and 250 patients with a stimulated cortisol<420 nmol/L (biochemical adrenal insufficiency) are randomised 1:1 to supplemental hydrocortisone or placebo during mild to moderate stress ('sick-days') for 6 months or until daily prednisolone is stopped. The goal is 200 patients completing ≥3 months intervention period. Patients continue prednisolone tapering according to PMR/GCA guidelines. In the event of severe stress (risk of adrenal crisis), patients receive open-label hydrocortisone treatment. 95 patients with stimulated cortisol ≥420 nmol/L serve as control group. The primary outcome is HRQoL measured as fatigue using ecological momentary assessments (EMA) of the General Fatigue scale from the Multidimensional Fatigue Inventory-20, five times daily in situations of stress ('sick-days'). EMA will be administered via a smartphone application 'EMA live'. Differences in mean fatigue scores during sick-days between hydrocortisone and placebo will be analysed using mixed models for repeated measures. Secondary outcomes include daily smartphone-based symptom reporting, additional HRQoL questionnaires, adrenal crises, adverse effects from glucocorticoid excess, serial ACTH tests and biomarkers of adrenal insufficiency. The study is approved by the Ethics Committee of the Capital Region of Denmark and the Danish Medicines Agency. Recruitment began June 2022. The last patient's last visit is expected in 2026. Results will be disseminated via peer-reviewed publication and conference presentations. EudraCT:2021-002528-18, CTIS:2024-518272-30-00, NCT05435781.
Early diagnosis of colorectal cancer (CRC) can significantly improve prognosis, but currently there is a lack of simple and effective screening methods in clinical practice. This single-center retrospective study included patients with CRC and benign colorectal polyps (BCP) diagnosed at our hospital between December 2020 and December 2023, as well as healthy controls (HCs). Eligible participants were randomly assigned to a training cohort and an internal validation cohort in a 7:3 ratio. Univariable and multivariable logistic regression analyses were performed in the training cohort to identify independent diagnostic predictors of CRC. A diagnostic nomogram was then constructed based on these predictors and internally validated. Six hundred forty seven CRC, 365 BCP, and 400 HC were ultimately included in the study. Univariate and multivariate analysis showed that sex, HB, CEA, CA19-9, CONUT score, and HALP score were independent diagnostic predictors associated with CRC. The internal validation results indicated that the predictive ability of the nomogram (AUCnomogram = 0.896) is significantly stronger than that of each individual indicator (AUCHB = 0.78, AUCCEA = 0.73, AUCCA19-9 = 0.72, AUCCONUT = 0.64, AUCHALP = 0.72) (p < 0.05). The calibration curves confirmed the high consistency between the predicted probability and observed probability of the nomogram, and the decision curve analysis demonstrated its good clinical utility. This study integrated multiple independent diagnostic predictors of CRC and developed an internally validated diagnostic nomogram with good discrimination and calibration in this single-center retrospective cohort.
Palliative care clinicians are regularly exposed to emotionally laden situations. While emotions are an intrinsic part of their encounters with patients and relatives, the role of clinicians' own emotions has remained understudied. We aimed to explore how palliative care clinicians use their emotions during end-of-life care consultations. We conducted a qualitative study using individual interviews with palliative care clinicians from different backgrounds and countries. Twenty-two palliative care clinicians from 10 different countries participated: two psychologists, four social workers, five nurses, and 11 physicians. Fourteen were women. Participants had an average age of 45 years and 13 years of palliative care experience. We analyzed the data using a social constructivist grounded theory approach. The process of using emotions could be understood as a three-phase process which was set off by a difficult end-of-life encounter (e.g., ethical dilemmas or conflicts, confrontations with the emotions of patients/relatives) that triggered a strong emotion. Subsequently, clinicians became aware of the specific emotion via its physiological and/or psychological cues. Secondly, an assessment of the appropriateness of sharing the emotion followed, in which facilitators and barriers (e.g., the self-perceived level of emotional skills, the feeling of safety in the team) interplayed, influencing the clinicians to, in a final phase, decide to share their own emotions in a verbal and/or non-verbal way. All phases of the process were interconnected by the shared value of using emotions to build connection, the core category of the theory. Our findings suggest that palliative care clinicians use their strong emotions during consultations to build connection. When met with awareness and reflection, these emotions can serve as a valuable resource for delivering patient- and relationship-centered palliative care. Future research should explore clinicians' training needs and attitudes towards emotional skills training more broadly.
The Collaborative Care Model (CoCM) is a principle-based, behavioral health integration model used in primary care to improve access and quality of behavioral health treatment. CoCM was originally developed and tested for the treatment of depression. This JGIM Perspective argues that when principle-based models are scaled to complex populations and settings beyond those for which they were originally developed, the boundaries of the principles are strained. In scaling CoCM for the treatment of opioid use disorder (OUD) co-occurring with PTSD and/or depression in a randomized trial, we found challenges with enacting the principles of CoCM for a complex population in low-resourced settings. Key considerations included understanding the scope of the care manager role while adapting practices for low-resourced settings (e.g., using community health workers (CHWs) in the role; delivery of psychotherapy by CHWs), understanding if and how to address patient social needs in CoCM care plans, overcoming lack of validated measures for OUD symptoms, and understanding the appropriate timeframe and supports needed to provide population-based care to complex patients with co-occurring disorders. Practitioners, researchers, and policymakers should collaborate to refine understanding of the CoCM principles to strengthen the foundation of CoCM and its application to various populations and settings.
Physical restraints and antipsychotics should only be used as a last resort in hospitalized individuals at risk of harm to themselves or others. Since verbal reorientation and de-escalation are first-line management in these scenarios, patients with limited English proficiency (LEP) may be at higher risk of physical restraint and antipsychotic use. We aimed to examine the relationship between English proficiency, physical restraints, and antipsychotic use in hospitalized adults. Retrospective cohort study of adults discharged from an academic medical center between 1/2019 and 6/2023. LEP was defined by non-English primary language listed in the electronic medical record. The primary outcome was use of either physical restraints or antipsychotics during the hospitalization, defined by orders and pharmacy charges, respectively. Multivariable generalized estimating equations were used to examine the relationship between primary language and outcomes, controlling for demographic, hospitalization, and clinical characteristics. The cohort consisted of 132,767 hospitalizations (mean age 62.9 years, 48.3% female, 10.8% with LEP). Either physical restraints or antipsychotics were used in 14,802 (11.2%) hospitalizations. Unadjusted outcome rates in LEP and non-LEP groups were similar (10.1% vs. 11.3% for either physical restraints or antipsychotics, 7.9% vs. 8.9% for physical restraints, and 4.9% vs. 4.9% for antipsychotics). However, LEP patients had higher adjusted odds of either physical restraint or antipsychotic use (aOR 1.18; 95% CI, 1.08-1.28), physical restraint use (aOR 1.30; 95% CI 1.17-1.43), and antipsychotic use (aOR 1.12; 95% CI 1.01-1.25). Subgroup analysis among patients with diagnosed delirium revealed an even stronger association between LEP and the primary outcome (aOR 1.42; 95% CI 1.22-1.65). This single center study found language-based disparities in orders for physical restraints and antipsychotics among hospitalized patients. Given the potential risks associated with both physical restraints and antipsychotics, causes and mitigators of this disparity should be investigated.
Work-related musculoskeletal disorders are highly prevalent among healthcare professionals and contribute to disability, reduced productivity and compromised patient care delivery. The Extended Nordic Musculoskeletal Questionnaire is a comprehensive tool used for gathering data on musculoskeletal symptoms and their impact, however its measurement properties have not been validated in Singapore. This study aimed to evaluate the reliability and validity of the extended Nordic Musculoskeletal Questionnaire in measuring musculoskeletal disorders (MSDs) among healthcare professionals in two community hospitals in Singapore. A total of 251 nurses and therapists working in two community hospitals were recruited in a cross-sectional study conducted between March 2024 and August 2024, following the Consensus-based Standards for selection of Health Measurement Instruments framework (COSMIN). Face validity was assessed through cognitive debriefing interviews (CDIs). Construct validity was assessed by testing 5 a priori hypotheses with the EQ-5D-5L instrument, using Spearman's correlation coefficients. Test-retest reliability was evaluated using kappa, observed proportion of agreement and intraclass correlation coefficient (ICC), while the internal consistency was determined using Cronbach's alpha. Among 251 participants (mean age: 34.7, 83.6% females, 7.31 years of working experience), the NMQ-E demonstrated good internal consistency (Cronbach's alpha above 0.81), and excellent test-retest reliability [ICC = 0.987 (95% CI 0.974-0.994)] with moderate to almost perfect reliability (kappa = 0.64-0.95). All a priori were confirmed in convergent validity assessment. Item response rates exceeded 97%, indicating good feasibility. The NMQ-E is a valid and reliable instrument for assessing work-related musculoskeletal symptoms among healthcare professionals in community hospitals within Singapore. Its application may greatly support epidemiological surveillance and inform occupational health interventions in Singapore's healthcare setting.
Hemodialysis patients experience significantly lower quality of life compared to the healthy individuals, largely due to symptoms such as bone pain, fatigue, pruritus, anorexia, inflammation, malnutrition, and anemia. This study aimed to investigate the effects of sarcopenia and low muscle mass on quality of life, with a particular focus on physical health indices. The study included 62 patients on maintenance hemodialysis. Sarcopenia was diagnosed using the fat-free mass index (FFMI), defined as skeletal muscle mass divided by height squared (kg/m²). Additionally, skeletal muscle mass was normalized to body surface area (BSA); values below the sample mean of 46.12 kg/m² were classified as low muscle mass. Quality of life was assessed with the Kidney Disease Quality of Life (KDQOL) Version 1.3 questionnaire and scored using the KDQOL-SF™ Version 1.3 Scoring Program. Sarcopenia was present in 18 patients (29%) according to FFMI. Patients scored lowest in general health (35.6), energy/fatigue (40.9), and both SF-12 physical (37.5) and mental health (37.2) domains. Sarcopenic patients reported significantly higher pain scores (60.97 ± 29.54 vs. 46.19 ± 27.37; P = .046), but other domains did not differ. Patients with low muscle mass/BSA (kg/m2) had lower sleep (51.5 ± 11.7 vs. 59.6 ± 13.0; P = .01), energy/fatigue (35.6 ± 20.1 vs. 52.8 ± 20.7; P = .005), and SF-12 physical health scores (35.7 ± 9.0 vs. 40.6 ± 8.3; P = .03). Muscle mass indexed to BSA was an independent predictor of the SF-12 physical health composite score. Low muscle mass, particularly when indexed to BSA, is associated with reduced physical health in hemodialysis patients and poorer quality of life across multiple domains. BSA-indexed muscle mass showed stronger and more consistent associations than FFMI-based definitions.
Medical residency is a transformative but emotionally intense period, marked by long hours, constrained autonomy, complex hierarchies, and existential challenges. While the literature widely acknowledges consequent burnout, the "burnout" framework may not encompass the range of residents' emotional experiences or account for institutional and developmental influences. This article synthesizes qualitative research on US and Canadian medical residents' work-related emotional experiences to elucidate: (1) applications of qualitative methodology for understanding residents' work-related emotional experiences, (2) dynamics and causes of such experiences, and (3) gaps in knowledge. We queried Medline, Embase, Web of Science, and Cochrane for studies published between 1952 and 2023. Our search initially yielded 11,555 records, manually deduplicated to 9486. We applied strict inclusion criteria for population, method, and topic, yielding 56 articles for analysis. Using a structured template, we abstracted study characteristics. We conducted descriptive analysis of discrete article characteristics and thematic analysis of article findings. We generated three major themes: Identity and Development, Interpersonal Dynamics, and Structural Dynamics. Our core finding was that residents' work-related emotional experiences emerged from dialectical interaction between an evolving identity and residency's challenges, with various interpersonal and structural factors influencing that interaction. The literature suggested it was not exclusively work that generated work-related emotions, but rather the interplay between work and issues of the developing self. Residents' work-related emotions arise from the ways their values and identities interact with the rigors of a prolonged "baptism by fire." Work challenges, identity development, interpersonal interactions, and systemic factors combine in multilayered, oft-unpredictable ways to produce subjective experiences that encompass more than just "burnout." Our findings suggest that resident well-being interventions must go beyond logistical and psychological interventions, directly addressing the deeper, existential challenges inherent to transitioning from student to physician.
Clinicians often struggle with asking patients with progressive, life-limiting illnesses about the point at which pursuing longevity no longer aligns with their values. While person-centered care encourages exploring patients' goals and fears, directly asking individuals to identify conditions "worse than death" can inadvertently reinforce ableist assumptions that disability diminishes quality of life. Yet avoiding these discussions risks neglecting patient autonomy and failing to align treatment decisions with what matters most. This Perspective examines the ethical tensions clinicians face when discussing life-prolonging treatments and perceived intolerable states. Through a clinical case and review of current frameworks, we highlight how traditional approaches, often focused on functional decline, may unintentionally pathologize disability. We argue for a strength-based, person-centered approach that shifts conversations from identifying feared states to understanding sources of meaning, identity, connection, and purpose. Asking patients what helps them feel like themselves, what they value most, and what sustains their sense of dignity can yield actionable clinical guidance without relying on assumptions about suffering or worth. This reframing supports care plans that balance the desire to avoid harm with the preservation of autonomy and personhood, fostering end-of-life care that honors everyone's values, experiences, and definition of living well.
Hospital healthcare professionals working during military conflicts experience extreme psychological pressure, yet the accompanying inflammatory responses in such real-world high-stress settings remain poorly characterized. In October 2023, during nationwide missile attacks in Israel, hospital staff had to continue routine clinical duties. To examine the association between biological and psychological profiles of healthcare professionals during a stressful wartime. A prospective cohort study. Ninety healthy hospital employees from central Israel volunteered to participate. Psychological distress was measured using the Patient Health Questionnaire-4 (PHQ-4), and perceived stress was assessed using the Perceived Stress Scale-4 (PSS-4). Serum concentrations of interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were quantified using ELISA assays. Associations between psychological measures and cytokine levels were evaluated using linear regression analyses. Multiple linear regression analysis showed that psychological distress was associated with IL-1 production (p = 0.0265; 95% CI, 0.009543-0.1502), whereas no significant associations were observed for IL-6 (p = 0.4624; 95% CI, 0.08931-0.04098) or TNF (p = 0.5235; 95% CI, -0.9145 to 1.783). Multiple linear regression analysis showed that mental stress was associated with IL-1 production (p = 0.003; 95% CI, 0.04567-0.1486), whereas no significant associations were observed for IL-6 (p = 0.7084; 95% CI, -0.05985 to 0.04087) or TNF (p = 0.9761; 95% CI, -1.058 to 1.027). These findings demonstrate that psychological distress and mental stress experienced by healthcare professionals during wartime are accompanied by measurable increases in circulating cytokines. Inflammation may serve as an objective biomarker of psychological burden in extreme conditions and could inform future strategies to monitor and support the mental health of hospital healthcare professionals during crises.
Esophageal adenocarcinoma (EAC) represents one of the most increasing malignancies in Western countries. The disease is multifactorial, involving modifiable risk factors and genetic susceptibility variants. These variants can be aggregated to a polygenic risk score (PRS) that reflects individual genetic risk. Investigation of the effects of lifestyle factors, PRS, and co-medication on EAC age at onset (AAO) is critical for shaping prevention strategies. A detailed questionnaire was used to assess pre-diagnostic exposure to lifestyle factors and clinical information from a large German EAC cohort. Linear regression analysis was performed to identify factors associated with EAC AAO in 1742 EAC patients. PRS was available for 1190 patients. Subgroup analyses were conducted to estimate the effects of the analyzed factors on AAO according to age group (early vs. late onset), sex, and prior diagnosis of Barrett's esophagus (BE). Earlier AAO was significantly associated with gastroesophageal reflux (GER), smoking and a higher PRS, whereas later AAO was associated with physical activity and higher consumption of fish and fruits. Among co-medication, combined use of proton pump inhibitors (PPIs) and acetylsalicylic acid (ASA) showed the most significant effect on AAO, whereas the use of PPIs and ASA alone showed weaker effects. This study represents the largest questionnaire-based analysis to date investigating factors influencing EAC development. Our findings show that the combined use of PPIs and ASA, both cost-effective medications, is associated with delayed EAC onset. In addition, lifestyle and genetics contribute to EAC AAO.
Multiple myeloma (MM) develops through asymptomatic precursor stages characterized by progressive remodeling of the bone marrow (BM) immune microenvironment and disruption of bone homeostasis. To delineate changes in natural killer (NK) cell states during disease evolution, we investigated coordinated immune-tumor remodeling by integrating NK cell functional states with plasma cell-intrinsic susceptibility programs derived from CRISPR-based screens across healthy donors (HD), monoclonal gammopathy of undetermined significance (MGUS), smoldering MM (SMM), and newly diagnosed MM patients. The integration of NK cell state-associated gene signatures with plasma cell transcriptional programs revealed stage-specific co-variation between immune and tumor compartments. Public single-cell RNA sequencing datasets were interrogated to resolve NK cell heterogeneity, identifying cytotoxic CD56dim and regulatory CD56bright subsets. NK cell dynamics displayed stage-dependent changes, with early expansion followed by the contraction of CD56dim cells in BM, whereas CD56bright cells showed predominantly compositional remodeling. Within the CD56bright subset, transcriptional changes included an increased expression of KLRC1 (encoding NKG2A), subsequently validated by multiparametric flow cytometry. In parallel, plasma cell programs associated with NK sensitivity progressively decreased along disease stages, supporting tumor adaptation to immune pressure. The NKG2A ligand HLA-E displayed selective expression within CD16+ monocytes and followed a distinct variable pattern across disease stages, highlighting a microenvironmental contribution to NK cell regulation. Collectively, these findings indicate a coordinated process of immune-tumor co-evolution, characterized by dynamic remodeling of NK cell states and plasma cell susceptibility, with the NKG2A-HLA-E axis emerging as a central interface during MM progression.
A systematic review recommended seven multimorbidity indices for predicting mortality. However, their performance has not been assessed in a head-to-head comparison. We externally validated these indices and determined their performance compared to counting co-occurring diseases. Within the prospective Rotterdam Study in the Netherlands, we constructed seven specific sub-cohorts, selected from 14 926 community-dwelling older adults to match the target population of the selected multimorbidity indices. We calculated prediction scores according to the indices' original methods and used these as predictors in logistic regression models with all-cause mortality as outcome. We assessed their performance and compared it to four benchmark models fitted on the same index-specific samples. These models were based on (i) age and sex; (ii) counts of co-occurring diseases, age and sex; (iii) counts of co-occurring diseases associated with mortality, age and sex; and (iv) individual diseases as separate predictors, age and sex. The total population sizes of the seven sub-cohorts ranged from 2409 to 9045 participants. The mean age of the populations ranged from 59.4 to 77.0 years; the proportion of women ranged from 56.0% to 61.8% (excluding single-sex indices). The absolute risk for mortality ranged from 0.9% to 13%. Discriminative performance of the indices and corresponding count models was nearly identical across all indices (maximum difference in C-statistic: 0.06), yet higher than age-and-sex models. Absolute accuracy of the prediction scores was similar across all models (maximum improvement in Brier score: 4%). Calibration was poor in four out of seven indices, all of which had a follow-up time of 2 years or less. Counting co-occurring diseases is as accurate in predicting all-cause mortality in the general population as using multimorbidity indices. These findings imply that counting diseases is the more practical and reliable way of providing prognosis to patients with multimorbidity in a population of community-dwelling adults.