Clinical Epidemiology

Background Graft versus host disease (GVHD) remains a major determinant of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (allo HSCT). Existing GVHD prediction models demonstrate modest discrimination and limited generalizability, and calibration drift across external populations is rarely characterized despite its essential role in the clinical interpretability of predicted probabilities. Objectives To develop and externally validate an explainable machine learning framework for predicting acute and chronic GVHD and associated overall survival in patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndromes (MDS) undergoing allo HSCT, and to systematically characterize calibration across heterogeneous external validation cohorts to inform deployment requirements. Study Design The model was developed on three publicly available registry-derived datasets (N = 2,509) and externally validated across six independent cohorts (N = 14,788) comprising adult and pediatric allo HSCT recipients, including a regional Middle Eastern cohort (UAE and Jordan). A standardized preprocessing pipeline harmonized heterogeneous datasets. Gradient boosting models (CatBoost) were used for binary GVHD prediction; exploratory overall survival analysis used a Cox proportional hazards model with predicted acute GVHD risk as a covariate. Discrimination (AUROC with bootstrap 95% CI), calibration (logistic recalibration intercept and slope with analytical 95% CI), and feature importance (SHapley Additive exPlanations, SHAP) were assessed in training out-of-fold and all external cohorts. Results In internal validation, AUROC was 0.63 (95% CI 0.61-0.65) for acute GVHD and 0.72 (95% CI 0.70-0.74) for chronic GVHD. External validation demonstrated AUROC ranges of 0.51-0.57 (acute) and 0.54-0.64 (chronic), with consistent performance across disease subgroups despite substantial heterogeneity in transplant practices and feature availability. In exploratory survival analysis, the acute-GVHD-informed Cox model achieved a training-cohort C-index of 0.679 (95% CI 0.658-0.697); external C-indices ranged from 0.47-0.53. Calibration analysis identified systematic external risk overestimation (negative calibration intercept in 10 of 11 evaluable external cohort-target combinations) with heterogeneous slope drift requiring cohort-specific recalibration. Key predictors included recipient age, graft source, conditioning intensity, GVHD prophylaxis, and HLA match ratio. Conclusions An explainable, externally validated GVHD prediction framework was developed using heterogeneous registry-derived datasets, with systematic characterization of calibration drift across multiple external cohorts, an analysis rarely reported in prior GVHD prediction literature. Predictive performance was modest for acute GVHD and moderate for chronic GVHD, constrained by missing immunobiological variables and incomplete HLA characterization. Per-cohort recalibration is required before clinical deployment, with prospective validation and benchmarking against established GVHD risk scores identified as priority next steps.

Aim: The global population of older adults is growing, and older age is linked to higher bleeding risk. Although guidelines discourage aspirin for primary prevention in healthy older adults due to bleeding harms outweighing benefits, many continue taking it without a clear indication. It remains unclear whether all older adults face uniform aspirin-related bleeding risk or if certain subgroups are more vulnerable. Methods: We analyzed data from 19,114 ASPREE trial participants to develop machine learning models using 116 baseline variables. Random forest (RF) and random survival forest (RSF) models predicted 5-year bleeding risk, and participants were stratified into low, intermediate, and high-risk groups based on the 20th and 80th percentiles of predicted risk. We assessed heterogeneity of treatment effect (HTE) by testing treatment-by-risk group interactions on the relative scale using Fine-Gray models, and on the absolute scale using observed 5-year cumulative incidence rates. Results: Over a median follow-up of 4.7 years, 626 major bleeding events occurred. The RF model had moderate discrimination (AUC = 0.65, 95% CI: 0.63-0.67) and good calibration (Brier = 0.032, 95% CI: 0.029-0.034). Statistically significant HTE was observed on the relative scale, with the greatest relative increase in bleeding risk seen in the low-risk group (subdistribution hazard ratio = 2.26, 95% CI: 1.27-4.01). On the absolute scale, low-risk participants experienced higher bleeding with aspirin (absolute risk difference (ARD) = 1.17%, 95% CI: 0.37-1.95), but heterogeneity in ARDs was not statistically significant (Cochran's Q p > 0.45). Similar findings were observed when using the RSF model. Conclusion: Participants at lowest baseline bleeding risk experienced the greatest relative increase in bleeding risk with aspirin therapy. We found statistically significant heterogeneity in treatment effects on the relative but not absolute scale. These findings support an individualized, risk-based approach to aspirin therapy decision-making in older adults.

Background The incidence of post-operative periprosthetic femoral fractures (POPFFs) is increasing. However, specific clinical guidance relating to patient management does not exist, resulting in variations in care and outcomes. This study aimed to elicit and synthesise expert knowledge in POPFF service delivery and explore views on variations in service provision and the factors influencing these. Methods Semi-structured interviews were undertaken with healthcare professionals with expertise in POPFF care from England and Wales to explore current practices, challenges, service variations and perceived future opportunities. Participants were identified through specialist research and clinical networks for POPFF and hip fracture care, authors of key publications on the subject, national leads for POPFF/hip fracture networks, and research team contacts. Interviews were analysed using thematic analysis. Results Ten interviews were undertaken with experts in POPFF services across a range of professional roles. Four themes were identified: conceptualisation of POPFF (by different professional groups and in different service settings) and understanding of POPFF patient needs; sources of variation in management and care of POPFF patients; service model rationales, advantages and disadvantages; and potential strategies to improve POPFF care. Conclusion When designing POPFF services, we suggest that four key areas need consideration: the extent to which POPFF patients are a distinct group with particular care needs; the necessity for and consequences of patient transfer between wards and hospitals; the resourcing of extensive multidisciplinary support for POPFF patients; and the need for national initiatives to encourage service developments. These findings should form the basis of future clinical guidance. Sensitivity to contextual factors driving variation in services is needed to ultimately improve care for POPFF patients.

IntroductionCervical spondylotic myelopathy (CSM) surgery is frequently associated with residual neurological deficits, partly due to unrecognized dynamic spinal cord compression on conventional MRI. Current static imaging may miss position-dependent stenosis, resulting in insufficient or inappropriate decompression. This study aims to evaluate whether dynamic MRI-guided individualized surgery improves neurological outcomes compared to conventional MRI-based planning. ObjectivesThis study aims to examine the association between dynamic MRI-guided surgical planning and neurological recovery in cervical spondylotic myelopathy, and to evaluate its role in identifying responsible segments, avoiding excessive surgery, and improving clinical outcomes. MethodsThis single-center retrospective cohort study will include 300 patients who underwent cervical spine surgery between January 2020 and December 2025 at the First Affiliated Hospital of Guangxi University of Chinese Medicine. Patients will be categorized into the dynamic MRI-guided group (n=150) or conventional MRI-based group (n=150) based on preoperative imaging modality. 1:1 propensity score matching will be performed using age, sex, BMI, disease duration, baseline mJOA score, and number of compressed segments. The primary outcome is the rate of improvement in the mJOA score at 6 months postoperatively. Secondary outcomes include VAS, NDI, reoperation rate, and time to first complication. Between-group comparisons will use t-tests/Mann-Whitney U tests for continuous variables, {chi}{superscript 2} tests/Fishers exact tests for categorical variables, and Kaplan-Meier estimates with the log-rank test for time-to-event outcomes. A two-sided P<0.05 will be considered significant. Analyses will be performed using R software (version 4.4.1). Ethical approval was obtained from the Medical Ethics Committee of the First Affiliated Hospital of Guangxi University of Chinese Medicine (Approval No. 2025-080-KY-01) from February 06, 2026 to February 05, 2027. Expected outcomesWe hypothesize that dynamic MRI-guided surgical planning will improve neurological recovery and decompression accuracy in cervical spondylotic myelopathy, providing evidence for optimized preoperative imaging and precision spine surgery. Trial registrationChiCTR2600122088

Chronic postsurgical pain (CPSP) prevalence after total knee arthroplasty (TKA) is >20%. Circulating immune biomarkers are known factors of musculoskeletal pain but poorly understood as CPSP predictors. This prospective, longitudinal study of 203 patients s/p TKA tested presurgical plasma biomarkers associated with 6-month CPSP, using promising approaches from geriatrics biomarker research: expected recovery differential (ERD; resilience outcome) and penalized, machine-learning regularization modeling (elastic net and LASSO regression). Forty-nine presurgical candidate biomarkers were considered. CPSP was operationalized using ERDs built around PROMIS pain intensity and pain interference, which quantified the difference between observed and expected recovery after accounting for demographic, comorbidity, reserve, and perioperative factors. Plasma/ERDs from ~130 patients revealed 13 biomarkers with the highest selection stability criteria, and either positive or negative (+/-) associations with ERDs. Interleukin (IL) 5 (-) and Lipopolysaccharide-Binding Protein (LBP; +) were associated with both ERDs. Unique associations with pain intensity ERD included Cytomegalovirus-Specific IgG Negative (CMV IGg-; -), Macrophage Inflammatory Protein-1 Beta (MIP1b; -), IL12p70 (-, Cluster of Differentiation 30 (sCD30;-), Interferon alpha 2a (IFN2a;+), and Leukemia Inhibitory Factor (LIF;+). Unique associations with pain interference ERD included Lipopolysaccharide (LPS;-), Activin A (-), IL8 (-), Serum Amyloid A (SAA;-), and IL7 (+). Protein-protein interaction analyses and topology motifs suggest a centralized network with higher-than-expected connectivity, involving IL5, IL7, IL8, MIP1{beta}, and IFN2a, among others. This study proposes rigorous yet feasible approaches to expedite pain biomarker research, and introduces presurgical biomarkers t0 consider in future TKA-CPSP biosignature derivation.

Background Annually, nearly 2 million hip, knee, and spinal inpatient surgeries are performed in Canada and the US for osteoarthritis (OA), costing over $37 billion in hospital expenditures. However, 15-30% of patients experience limited or no improvement, resulting in poor value for money. This study evaluated the one-year cost-utility of joint and spine procedures for OA by comparing non-responders to responders, considering various responder definitions. Methods Individual micro-costing data were collected for 1,175 elective hip, knee, and spine patients enrolled in the Longitudinal Evaluation in the Arthritis Program - Osteoarthritis (LEAP-OA) between 2014 and 2018. Quality-adjusted life years (QALYs) were derived using the SF-6D utility index. One-year incremental cost-utility ratios (ICURs) were calculated from the hospital perspective. Results Responder rates varied by definition, ranging from 78%-94% for hip replacements, 64%-90% for knee replacements, 60%-64% for spine fusions, and 50%-68% for spine decompressions. Corresponding ICURs were: $45,956-$51,773/QALY for responders versus $108,593-$485,762/QALY for non-responders for hip replacements; $54,831-$71,151/QALY for responders versus $200,486-$1,203,596/QALY for non-responders for knee replacements; $65,980-$74,422/QALY for responders versus $262,039-$729,686/QALY for non-responders for spine fusions; and $29,947-$42,168/QALY for responders versus $63,195-$662,586/QALY for non-responders for spine decompressions. Conclusions While surgical response rates were highly dependent on the responder definition, ICURs for non-responders were significantly higher than those for responders across all definitions. Beyond the negative impact on patients, there is a compelling economic argument for investment in improved pre-operative identification of patients at risk of surgical non-response. Such efforts could enable more personalized, value-based care pathways and reduce the provision of low-value surgical interventions.

Introduction: Acute compartment syndrome (ACS) is a limb-threatening complication of extremity trauma that requires timely diagnosis to prevent irreversible muscle and nerve injury. Current diagnostic methods are invasive, intermittent, and operator-dependent. We evaluated the feasibility of a novel, Bluetooth-enabled electrical impedance myography (EIM) device (mAlert, Myolex, Inc., Brookline, MA, USA) for continuous, noninvasive detection of ACS-related tissue changes. Methods: Ten Yorkshire swine underwent anterior tibial compartment monitoring using three ACS models: albumin infusion (ALB, n=3), femoral artery and vein ligation (LIG, n=3), and combined albumin infusion plus ligation (ALB+LIG, n=4). Resistance (R), reactance (X), and phase (P) were measured every minute across 1 to 199 kHz alongside continuous intra-compartmental pressure (ICP) monitoring. Group differences in normalized impedance trends were evaluated using the Kruskal Wallis test with Dunn post hoc correction. As a proof-of-concept human study, nine healthy volunteers wore the device for up to five days to assess electrode durability and signal stability. Tissue ischemia was validated using pimonidazole immunohistochemistry. Results: ALB infusion produced progressive, frequency-dependent decreases in R, X, and P, whereas LIG produced consistent increases in R and X across frequencies. The ALB+LIG model generated mixed responses, reflecting the competing effects of edema and ischemia. Normalized phase slopes differed significantly among groups (H=6.14, p=0.046), with post hoc testing showing significant divergence between the ALB and LIG models (p=0.041). Control limbs remained stable throughout monitoring. Pimonidazole staining confirmed hypoxic injury in the intervention limb. In the human pilot study, three participants completed five days of monitoring, demonstrating sustained signal acquisition, while electrode degradation limited data collection in the remaining participants. Conclusions: This preliminary feasibility study demonstrates that wearable EIM can continuously detect model-specific physiological changes associated with ACS in a large-animal model. These findings support further development and clinical evaluation of wearable EIM as a non-invasive monitoring technology for early ACS detection in trauma patients.

PURPOSE: As the armamentarium of BPH therapies continues to expand, it remains imperative to maximize patient satisfaction and minimize decisional regret. We sought to determine the impact of time from BPH diagnosis to index treatment on symptom improvement and subsequent procedural events. MATERIALS AND METHODS: We queried the American Urological Association Quality Registry for men [&ge;] 40 years old with BPH, available IPSS data, and no receipt of prior BPH treatment. Index treatment included medication, surgery, or minimally invasive surgical therapy (MIST). Outcomes included IPSS over 3 years of follow-up, change in percentage of mild lower urinary tract symptoms (LUTS) by 3 months, and time to procedural event. Patients were stratified by time from index diagnosis to treatment by <12 months, 1-3 years, and >3 years. Outcomes were compared across time-to-treatment cohorts with appropriate statistical tests with p < 0.05 as significant. RESULTS: 43,919 patients met criteria with 19,642 pursuing treatments. Patients pursued treatment at comparably lower baseline IPSS compared to prior prospective series. Patients undergoing surgery and MIST had significantly higher baseline IPSS, while medical comorbidities were significantly more common among men initiating pharmacotherapy. Early surgery and MIST were associated with significant improvement in IPSS within 6-12 months and an increase in mild LUTS by 3 months. All forms of early treatment were associated with delayed time to procedural events, including catheterization and fulguration. CONCLUSIONS: Early procedural intervention for BPH is associated with early symptom improvement and delayed time to procedural events among real-world, contemporary practice.

Rationale. Racial disparities in outcomes among patients with acute respiratory failure are well-described, but the contributions of clinicians to these disparities have not been evaluated. Objectives. Among mechanically ventilated patients, we evaluated racial disparities in severity of illness trajectories and adapted value-added modeling to quantify nurse and physician relationships with these disparities. Methods. In a retrospective cohort of mechanically ventilated patients across five hospitals between 2018 and 2022, we used generalized estimating equations to model the change in Laboratory-based Acute Physiology Score version 2 (LAPS) from the start to end of intensive care unit admission ({Delta}LAPS). Consistent with value-added modeling, we randomly allocated the cohort into development and testing partitions, and fit separate multiple linear regression models of {Delta}LAPS using concurrent nurse and physician assignments (determined at 4-hour intervals), patient race, and clinician-race interaction terms as fixed effects. Clinician-specific and clinician-race interaction coefficients were extracted to determine race-specific value-add for each clinician. We defined the race-contextual value-add difference (RCVAD) as a clinician-level measurement of the difference in that clinician's value-add between Black and White patients in their care; a positive RCVAD indicates a more favorable severity of illness trajectory for Black relative to White patients and vice versa. Measurement and Main Results. Among 6,555 distinct patients, 7,247 clinical encounters, 405 nurses, and 70 physicians, Black patients accounted for 2,926 (40%) encounters. Overall, Black patients had significantly less improvement in {Delta}LAPS than White patients (difference in LAPS decline = 2.26 [0.23, 4.29], p=0.029). In the development partition, median nurse RCVAD was -0.10 (interquartile range [IQR]: -1.17, 1.14) with 191 (47%) nurses having a positive RCVAD; median physician RCVAD was -0.18 (IQR: -1.34, 0.56) with 29 (41%) having a positive RCVAD. Conclusions. Black mechanically ventilated patients experience less improvement in severity of illness during intensive care unit admission than White patients. While the majority of physicians and nurses were associated with disparities-exacerbating illness trajectories, many other clinicians were associated with disparities-mitigating trajectories. Future work to understand practices associated with disparities-exacerbating and disparities-mitigating care profiles could inform interventions to reduce disparities overall.

Abstract Background:Sickle cell disease (SCD) is concentrated in sub-Saharan Africa, where delivery of guideline-referenced care remains challenging. Current evaluation approaches rely largely on access indicators and clinical outcomes, which do not directly measure care delivery. We developed the Care Delivery Gap (CDG) framework, a patient-reported approach for identifying care-process omissions, and conducted a proof-of-concept study to assess feasibility and explore variation across income strata. Methods: We conducted a cross-sectional framework-development study involving a proof-of-concept sample of 52 individuals with SCD or caregivers recruited through clinics and moderated SCD communities across Africa, North America, and Europe between June 2025 and March 2026. The CDG framework assessed patient-reported omissions in specialist involvement, follow-up continuity, cardiovascular screening, and biochemical surveillance. Analyses were descriptive. Results: Substantial multi-domain care-process omissions were identified despite high reported healthcare engagement. Across geographic income strata, cardiovascular screening was reported by 4/35 (11%) LMIC versus 16/17 (94%) HIC participants, and regular follow-up within the preceding 12 months by 14/35 (40%) versus 16/17 (94%), respectively. High CDG scores, representing 1 omissions across three or four domains, occurred in 20/35 (57%) LMIC compared with 1/17 (6%) HIC participants. Similar disparities were observed across specialist review and vitamin B12 surveillance domains. Conclusion: A structured patient-reported framework identified multi-domain omissions in guideline-referenced SCD care, including among individuals reporting healthcare access. The divergence between access indicators and reported care delivery suggests that service contact alone may not reflect care quality. The framework provides a feasible foundation for future process-level quality measurement in high-burden settings.

Background and Aims: Cardiovascular risk scores guide primary prevention, but their comparative performance remains uncertain. We externally validated 16 established and contemporary cardiovascular risk-prediction models in a common primary-prevention evaluation framework. Methods: UK Biobank participants free from cardiovascular disease and cancer at baseline were included. 16 models, corresponding to 19 configurations, were implemented as published and evaluated against a harmonized incident CVD endpoint. Performance at 5 and 10 years was assessed using discrimination, calibration, Brier score, decision curve analysis, and TRIPOD+AI reporting quality. Results: Among 438,640 participants, 45,003 incident cardiovascular events occurred over a median follow-up of 13.5 years. Ten-year area under the curve ranged from 0.668 for QRISK3 to 0.734 for PREDICT, and C-index from 0.655 to 0.717. Calibration varied substantially: PROCAM, Framingham, ASSIGN, and QRISK1 overestimated risk, whereas PREVENT, PREDICT, SCORE, SCORE2, SCORE2-OP, and China-PAR generally underestimated risk. QRISK2 showed the best calibration, while PREVENT had the lowest Brier score. At higher treatment thresholds, net benefit diverged, with PREVENT and PCE performing most consistently. Composite assessment favored PREVENT, QRISK2, PREDICT, PCE, and northern China-PAR variants. Conclusions: Direct application of cardiovascular risk scores across populations can produce clinically important differences in calibration and net benefit. Model selection for primary prevention should require external validation, local recalibration, and assessment of clinical utility, rather than reliance on discrimination alone. PREVENT, QRISK2, PREDICT, PCE, and northern China-PAR variants showed the most balanced performance in this cohort.

Purpose To explore patient and caregiver perspectives on factors influencing mobility during hospitalization after hip fracture surgery, and how these are experienced and negotiated in everyday hospital practice. Materials and methods A qualitative interview study informed by a hermeneutic-phenomenological perspective was conducted in a hospital setting in Denmark. Using purposive sampling with maximum variation, ten patients and nine caregivers were interviewed during hospitalization. Data were analyzed using reflexive thematic analysis following Braun and Clarke. Results Five interrelated themes were identified; (1) Body and mind in transition; (2) Communication as a prerequisite for safety and mobility; (3) Structural barriers and ambiguities in responsibility; (4) The physical environment and ward culture; and (5) Mobility as preparation for life after discharge. Across themes, mobility emerged as a socially shaped and negotiated practice through everyday interactions, communication, organizational routines, and situational support during hospitalization. Conclusions Mobility during hospitalization after hip fracture surgery emerged as a context-dependent and socially shaped practice rather than a purely physical task. These findings suggest that rehabilitation during hospitalization may need to attend not only to mobility prescription, but also to relational, communicative, and contextual aspects of everyday ward routines that shape patients' confidence and participation.

ObjectiveTo investigate the long-term (defined as [&ge;]12 months) prognosis of knee pain and knee function in adults and adolescents with patellofemoral pain (PFP). DesignSystematic review with meta-analysis and meta-regressions. Data sourcesMEDLINE, OVID, CENTRAL, Web of Science, OpenGrey, and International Patellofemoral Research Retreat abstract books. Eligibility criteria for selecting studiesProspective studies of patients clinically diagnosed with PFP, aged <40 years, with a long-term follow-up (minimum of 12 months). Primary outcomes were self-reported pain intensity (worst, during activity, and usual) and function. Meta-analyses and meta-regressions were performed where appropriate. Narrative synthesis was performed for those not included in the metanalysis. Risk of bias was assessed using the Quality In Prognosis Studies (QUIPS) tool, and certainty of evidence using GRADE. ResultsA total of 42 studies (n = 3,230) were included. At 12 months, meta-analysis indicated reduction in worst pain (SMD 1.36; 95% CI 0.85-1.86), pain during activity (SMD 1.36; 95% CI 0.61-2.11), and resting pain (SMD 0.91; 95% CI: 0.75- 1.08). No significant reduction was found for usual pain. We found improvement in self-reported function (investigated using the Anterior Knee Pain Scale (AKPS) MD 14.60; 95% CI 11.60-17.61), FIQ (MD 3.33; 95% CI: 2.46- 4.20) and the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) (MD -7.73; 95% CI: -10.36 to - 5.10). Extended follow-up ([&ge;]60 months) suggested more variable improvements. Meta-regression showed no association between age and 12-month function, while older age was modestly associated with greater improvement in activity-related pain at extended follow-up. Overall, a considerable proportion of participants continued to report persistent symptoms, and heterogeneity across studies was substantial. Certainty of evidence ranged from very low to moderate across outcomes investigated. ConclusionPain and self-reported function generally improve over time, particularly within the first 12 months. However, substantial heterogeneity and persistent symptoms in a considerable proportion of patients at extended follow-up indicate that recovery is not universal and trajectories are highly variable. What is already knownO_LIPatellofemoral Pain (PFP) is a very common condition in both adolescents and adults. C_LIO_LIMultiple treatments modalities exist, including patient education and exercise therapy. C_LIO_LIPeople suffering from PFP request more knowledge on the long-term prognosis. C_LI What are the new findings?O_LIThis systematic review and meta-analysis provide the most comprehensive synthesis to date of long-term outcomes ([&ge;]12 months) in adolescents and adults with patellofemoral pain. C_LIO_LIPain and self-reported knee function generally improve at the group level over time, particularly within the first 12 months. C_LIO_LIDespite group-level improvement, a substantial proportion of individuals continue to report persistent symptoms, indicating that patellofemoral pain is often not fully self-limiting. C_LIO_LILong-term outcomes are highly heterogeneous, with different pain constructs demonstrating distinct trajectories across follow-up periods. C_LIO_LIMeta-regression identified no consistent prognostic associations, suggesting that current study-level variables explain little of the variability in long-term outcomes. C_LI How might this study affect research, practice or policy?O_LIClinicians should communicate that while improvement is common in patellofemoral pain, persistent symptoms are frequent, highlighting the need for realistic prognostic expectations and long-term management strategies. C_LIO_LIFuture research should prioritise harmonised outcome measures and long-term follow-up to better understand recovery trajectories and identify subgroups at risk of persistent symptoms. C_LI

Background: Endovenous techniques are considered the gold standard for treating great saphenous vein (GSV) insufficiency, but access remains limited in low- and middle-income countries. In such contexts, simplified conventional surgeries may represent viable alternatives. This study aimed to compare outcomes of isolated GSV stripping with conventional surgery (stripping plus varicose vein resection) in patients with varicose veins (VV) associated with GSV insufficiency. Methods: A prospective interventional study was conducted including 34 patients with VV (CEAP C2-C6), divided into two groups: Conventional (C, n=17) and Isolated Saphenectomy (IS, n=17). Quality of life was assessed preoperatively and at 2 and 6 months postoperatively using the Venous Clinical Severity Score (VCSS) and VEINES-QoL/Sym questionnaires. Varicose vein evolution in the IS group was quantified using a standardized visual scoring system. Statistical analyses included Students t-test, chi-square, and generalized estimating equations (p[&le;]0.05). Results: Both groups were demographically comparable. Surgical treatment significantly improved VCSS and VEINES scores in both groups (p<0.005), with no intergroup difference at 6 months. In the IS group, the mean reduction in visible VV was 46% (range 20-90%). CEAP classification improved in both groups, with migration toward less severe categories postoperatively. No major complications were reported. Conclusion: Isolated GSV stripping yields comparable short- and mid-term improvements in symptoms and quality of life to conventional surgery, while reducing operative extent. In resource-limited settings, this abbreviated technique may expand access to treatment for VV, improving patient outcomes and reducing healthcare costs without compromising clinical efficacy.

BackgroundVenous thromboembolism (VTE) remains a major cause of perioperative morbidity in cranial neurosurgery, yet clinical practice varies widely, and formal guidelines are inconsistent. Understanding internationally sampled neurosurgical practice is essential for informing consensus and future trials. MethodsAn international, 2-stage cross-sectional, internet-based survey was conducted. Practising neurosurgeons performing elective adult cranial surgery were eligible. Descriptive statistics were used to summarise practice. Responses covered patterns of pre-operative haemostasis decision making, use and timing of mechanical and/or chemical prophylaxis, use of perioperative imaging prior to anticoagulation, and frequency of clinical assessment for VTE. Associations with geographical income status, subspecialty, and years post-certification were statistically tested. Practice heterogeneity was quantified and contextual influence was summarised using mean effect sizes across stratifying variables in order to determine domains of true equipoise. ResultsOf 585 responses, 456 (78%) met criteria for inclusion: representing 322 units across 78 countries (71% high-income). Thirteen per cent reported no departmental VTE plan; 23% followed no guidelines and 12% used multiple. Routine pre-operative testing almost universally included haemoglobin/platelets/haematocrit, with fibrinogen more common in high-income settings. Compared with high-income country respondents, low- and middle-income respondents reported higher haemoglobin transfusion thresholds (>90 g/dL; p<0.001) and shorter antiplatelet interruption (p[&le;]0.03), and less frequent outpatient VTE assessment (p<0.001). Mechanical prophylaxis was common (TEDs 81%, IPC 62%), typically started pre-or intra-operatively. Among those completing the chemoprophylaxis section (n=310), 57% required a CT or MRI scan before LMWH which was then initiated on average 31.4 hours after surgery. 1% of respondents did not routinely use LMWH. Many clinical decisions demonstrated statistical equipoise ie. high heterogeneity with low contextual influence. ConclusionPeri-operative haemostasis and VTE prophylaxis practices in adult elective cranial neurosurgery vary substantially worldwide, with some decisions reflecting geographical or socioeconomic differences and many others reflecting true clinical equipoise rather than contextual determinants. By mapping contemporary real-world practice across diverse health-system contexts, this study provides a necessary empirical foundation for rational trial design and future guideline development.

Background Hypercapnia may indicate a primary ventilatory syndrome, a complication of another illness, or an epiphenomenon of severe disease. The presenting context of hypercapnia is poorly quantified, limiting clinical interpretation and synthesis of epidemiologic studies. Methods We performed a retrospective cross-sectional study of Medical Information Mart for Intensive Care IV (MIMIC-IV) hospital admissions linked to an emergency department (ED) presentation from 2011 through 2019. Admissions were included if the triage chief complaint was not missing and at least one prespecified criterion for hypercapnia was met: an International Classification of Diseases (ICD) code for hypercapnic respiratory failure or obesity hypoventilation syndrome, arterial blood gas (ABG) PCO2 45 mmHg, venous blood gas (VBG) PCO2 50 mmHg, or indeterminate-source blood gas PCO2 50 mmHg. Triage chief-complaint text was classified by natural language processing (NLP) into 17 National Hospital Ambulatory Medical Care Survey reason-for-visit (RFV) categories using a multi-label framework. Primary analyses estimated admission-level RFV category prevalences; secondary analyses compared distributions by overlapping ascertainment indicator, age, and acidemia. Results The total cohort included 11,941 admissions: 1,542 (12.9%) met both blood-gas and ICD-code criteria, 9,958 (83.4%) met blood-gas criteria only, and 441 (3.7%) met ICD-code criteria only. Median age at admission was 68 years (IQR 56-78), and 6,423 admissions (53.8%) were for male patients. Respiratory RFV categories were most prevalent (30.2%), followed by administrative reasons (17.5%), digestive symptoms (14.0%), injuries and adverse effects (14.0%), and nervous-system symptoms (13.8%); categories were not mutually exclusive. Respiratory categories were more common in ICD-positive admissions (50.2%) than in VBG-defined (36.3%) or ABG-defined admissions (27.3%). Injuries and adverse effects were most prevalent among admissions for patients aged 18-39 years (34.4%), whereas respiratory categories increased from 13.7% among admissions for patients aged 18-39 years to 36.5% among admissions for patients aged 80 years. NLP-derived classifications showed mean set-F1 of 0.84 against adjudicated clinician labels in the full annotated benchmark sample. Conclusions Among ED-linked admissions with hypercapnia by diagnosis code, blood gas, or both, respiratory complaints were the most common chief-complaint category but represented fewer than one-third of admissions. Presentation context should be incorporated when defining, comparing, and interpreting hypercapnia cohorts, particularly those ascertained by blood-gas criteria.

BackgroundThe clinical assessment of knee stability after an Anterior Cruciate Ligament (ACL) injury is routinely conducted via operator-dependent physical examination tests (i.e. pivot shift) and standardized patient-reported outcomes. Unfortunately, both are unable to perceive and quantify the subtle rotational biomechanical deficiencies from an ACL tear. Although specialized laboratory-based motion capture systems may provide objective measurements, they are found in research institutions and thus, are not suitable for clinical use. In contrast, GATOR PRO is a clinic-based multimodal wearable sensor system that uses a machine learning (ML) model (ensemble deep learning) to differentiate and classify its data outputs for assessing in-vivo dynamic rotational knee stability. ObjectiveThe purpose of this study is to validate the deep machine learning model and its performance used in GATOR PRO, which integrates knee-mounted Inertial Measurement Units (IMUs) with ultrasound images to derive high-fidelity in-vivo biomechanical rotational data. Based on this data collected by the GATOR PRO, it is hypothesized that the model can effectively classify knee stability after ACL injury and reconstruction. MethodsThis prospective clinical study at Singapore General Hospital (SGH) (CIRB 2019/2766, PDPA-compliant) aimed to enroll 60 patients (30 ACL-deficient, 30 ACL-reconstructed [&ge;]6 months post-surgery). At the halfway point of the clinical trial, 29 patients (8 ACL-deficient, 21 ACL-reconstructed [&ge;]6 months post-surgery) were recruited through physician referral at SGH outpatient clinics to perform standardized chair-stand tests. An ensemble deep learning model that combines convolutional (EfficientNet) and time-series (InceptionTime) classifiers is used to output binary stability classifications (ACL-deficient/ACL-reconstructed). The models performance was evaluated using 10-fold stratified cross-validation with patient-wise splitting, repeated across 100 random seeds to assess variability. ResultsAt the halfway point of the trial, the ensemble model performance with regard to the Receiver Operating Characteristic area under the curve (ROC-AUC) was 0.8365 (SD: 0.042, p-value < 0.001), and the classification accuracy was 75.9% (SD: 3.2%) when the model was tested on the 29 CIRB-approved patients. For the ACL-reconstructed class, the performance indicators were as follows: precision 71.4%, recall 93.8%, F1-score 81.1%. For the ACL-deficient class, the indicators were: precision 87.5%, recall 53.8%, F1-score 66.7%.Against the clinical pivot shift tests low sensitivity (24-32%), the model delivers an almost 2X better sensitivity (53.8%)[2, 3], with a comparable specificity (93.8% vs. 90-98%) ConclusionThe multimodal machine learning model was able to perform at a level that was relevant to clinical classification (AUC-ROC 0.8365, accuracy 75.9%) in differentiating between ACL-deficient and ACL-reconstructed knees. Moreover, the model demonstrated far superior sensitivity than previously published estimates for manual pivot shift testing (53.8% vs. 24-32%). These findings demonstrate that rotational knee instability can be reliably differentiated in clinical settings with a ML model deployed on GATOR PRO data.

ABSTRACT/SUMMARYPulmonary arteriovenous malformations (PAVMs) larger than 4mm in size are estimated to affect 38 per 100,000 individuals [95% confidence intervals 18-76]. They provide an anatomical right-to-left shunt such that each heartbeat, a proportion of the cardiac output bypasses the pulmonary capillary bed, preventing essential processing functions such as gas exchange and filtration of blood-borne emboli. Although large cohort series were published in earlier decades, more recent data series have been scant. To support modern educational platforms, here we report features of 1149 consecutive patients with imaging-proven PAVMs, reviewed at a single UK centre between 1984-2026, including 813 (71%) with clinical and/or genetically confirmed hereditary haemorrhagic telangiectasia (HHT). The median age was 47y, and 735 (64%) were female. We report 4348 oxygen saturation measurements at presentation and follow-up, and 810 pulmonary artery pressure (PAP) measurements made at angiography prior to treatment of PAVMs by embolisation. Together, these confirm that there is no risk of hypoxic pulmonary hypertension, with PAP measurements higher in patients with higher SaO2. Massive haemoptysis or haemothorax occurred in 18 patients [0.009, 0.023], of which 7/18 [95% CI 0.01, 0.64] events were pregnancy-associated. Ischaemic strokes affected 125 patients [0.09, 0.13], brain abscess 107 patients [0.08, 0.11] patients, and haemorrhagic strokes 29 patients [0.02, 0.03] patients. These data will inform design of future work to evaluate aetiologies, associations and implications for clinical practice.

Background: Cardiovascular disease (CVD), cardiometabolic and neurocognitive conditions share risk factors and frequently co-occur. We evaluated whether four established CVD risk prediction models (QRISK3, PCE, SCORE2, SCORE2-OP) can be repurposed to predict 10-year risk of these conditions and their co-occurrence with CVD. Methods: The models were recalibrated using 20% of the UK Biobank (UKB) and evaluated in the remaining 80%. We performed external validation using data from Clinical Practice Research Datalink (CPRD) Aurum, assessing model discrimination (c-statistics) and calibration (intercept and slope). We used permuted feature importance to determine the influence of each individual predictor in the models. Results: Depending on the model, the c-statistics for incident CVD ranged from 0.71 to 0.74 in the UKB test set (16,137 events). Discrimination was equal to or higher than CVD when evaluated against non-traditional CVD outcomes: 0.74 to 0.77 for heart failure (3,471 events), 0.72 to 0.73 for atrial fibrillation (9,213 events), 0.73 to 0.75 for peripheral arterial disease (1,927 events) and 0.80 to 0.82 for abdominal aortic aneurysm (595 events). For the multimorbidity endpoints, model discrimination ranged from 0.74 for the composite of CVD and T2DM (SCORE2-OP) to 0.83 for the composite of CVD and dementia or Parkinson's disease (QRISK3). When considering the onset of any cardiovascular, cardiometabolic, or neurocognitive outcome discrimination ranged from 0.71 to 0.72. The repurposed models slightly underestimated the predicted risk in the CPRD compared to the UKB: average difference in calibration intercept was at most -0.64. After age and sex, smoking status and systolic blood pressure contributed most to model predictions. Conclusions: Repurposed CVD models can be used to identify 10-year risk of many CVD-related conditions and their multimorbidity. These may be used to support risk-based approaches to prevention and screening. The repurposed models have been made available at: https://repurposed-cvd-risk-models.shinyapps.io/cvd_cmd_dementia_app/ Keywords: Risk prediction; cardiovascular disease; cardiometabolic disease; dementia; disease prevention.

Introduction: Osteoarthritis (OA) is a chronic joint disease, often leading to pain, joint stiffness and impaired function. The first metatarsophalangeal (MTP-1) joint is the most frequently affected joint in foot OA. Footwear interventions might have potential to reduce pain for people with MTP-1 joint OA. The aim of this study is to determine the effectiveness and cost-effectiveness of orthopaedic modifications to off-the-shelf footwear in addition to usual care, compared to usual care alone, for people with MTP-1 joint OA. Methods and analyses: We perform a pragmatic, non-blinded, two-armed, parallel-group, randomised controlled trial (RCT). A total of 136 people with MTP-1 joint OA and presence of foot pain are recruited. Participants are randomised to orthopaedic modifications to off-the-shelf footwear in addition to usual care or to usual care alone. The footwear modifications comprise a combination of sole-stiffening, rocker sole adjustments and custom-made insoles. During a 12-month follow-up period, participants receive monthly questionnaires. Primary outcomes include walking pain at 6-month follow-up and quality-adjusted life years and societal costs at 12-month follow-up. Secondary outcomes include walking pain at 12-month follow-up and foot health, physical activity level, patient acceptability and self-reported recovery at 6- and 12-month follow-up. Intention-to-treat and per-protocol analyses will be performed using (generalised) linear mixed models. Ethics and dissemination: The study is approved by the local Medical Ethics Committee of the Erasmus MC University Medical Center Rotterdam, The Netherlands (MEC-2024-0615). Prior to study participation, participants provide informed consent. Results will be disseminated amongst researchers through peer-reviewed scientific articles and presentations at conferences; and amongst people with MTP-1 joint OA and healthcare professionals through layman articles in newsletters, on websites and on social media. Discussion: This is the first RCT to investigate the effectiveness and cost-effectiveness of orthopaedic modifications to off-the-shelf footwear in addition to usual care, compared to usual care alone for people with MTP-1 joint OA. Study findings will support healthcare professionals in making substantiated decisions in the treatment of people with MTP-1 joint OA.