The Lancet Rheumatology

Objectives To evaluate whether access to a certified large language model (LLM)-based clinical decision support system improves physician diagnostic performance in rheumatology compared with conventional diagnostic resources alone. Methods In this multicentre, open-label, randomised controlled trial, 82 physicians from seven hospitals in two countries were randomised 1:1 to conventional diagnostic resources plus Prof. Valmed or conventional resources alone. Participants assessed three rheumatology vignettes before and after assistance. The primary outcome was top-1 diagnostic accuracy. Secondary outcomes included top-3 accuracy, diagnostic reasoning, confidence, case-processing time and perceived support quality. Results Top-1 accuracy increased from 22.2% to 33.3% in the intervention group and from 23.3% to 35.0% in the control group, with no between-group difference in improvement (adjusted OR 0.99, 95% CI 0.45 to 2.19; p=0.979). Differences in top-3 accuracy, diagnostic reasoning and confidence were also not significant. Assisted case-processing time was substantially shorter with LLM support (94 vs 206 s; adjusted mean difference -112 s, 95% CI -141 to -83; p<0.001). Information timeliness and perceived diagnostic support quality were rated significantly higher in the intervention group. Exploratory analyses showed persistent overconfidence and substantial AI over-reliance. Conclusions Certified LLM-based diagnostic support did not improve diagnostic accuracy compared with conventional resources, but substantially reduced case-processing time and improved perceived support quality. These findings suggest potential workflow benefits while highlighting overconfidence and over-reliance as important safety considerations.

Background VEXAS syndrome is a late onset autoinflammatory disease caused by somatic UBA1 mutations and characterized by heterogeneous systemic and hematologic manifestations. We aimed to describe all identified Belgian cases through a national multicenter cohort. Methods We conducted a retrospective study across four Belgian tertiary centers. Clinical, biological, genetic, therapeutic, and outcome data were collected using standardized anonymized case report forms. Analyses were descriptive. Results Twenty-one male patients were identified between January 2018 and May 2025. General symptoms such as Fatigue, weight loss and sweating occurred in 95% of cases. The most frequent manifestations were cutaneous (85.7%), hematologic (76.2%), articular (66.7%), thromboembolic (57.1%), chondritis (42.9%), ophthalmologic (38.1%), pulmonary (38.1%). Other manifestations also included vasculitis (61.9%). At diagnosis, 95% had anemia, macrocytic in 57%, and 28.6% had thrombocytopenia. Corticosteroids were the main first line therapy. Second line treatments included anti IL 6 agents (46.7%), JAK inhibitors (20%), and azacitidine (14.3%). Complete remission occurred in 50% of patients receiving anti IL 6 therapy and in 33% treated with either JAK inhibitors or azacitidine. Two patients underwent allogeneic stem cell transplantation, one died from infectious complications. Twenty six infectious episodes were recorded, including opportunistic infections. Six patients (28.6%) died during follow-up, four from infectious complications. Conclusion This first Belgian national cohort confirms the clinical heterogeneity of VEXAS syndrome and highlights substantial infectious morbidity and mortality. Access to targeted second-line therapies, particularly anti IL-6 agents and JAK inhibitors, remains challenging despite apparent clinical benefit.

Importance: Immune checkpoint inhibitors (ICIs) produce diverse immune toxicities, but whether checkpoint blockade also modifies associations between other drugs and adverse events is poorly understood. Objective: To define ICI-associated toxicity organization and determine whether drug-associated adverse events and onset vary with ICI exposure and checkpoint pathway. Design and Setting: Cross-sectional analysis of deduplicated FAERS reports from 2016 through 2025; analyses performed in 2026. Participants: Among 13,701,106 deduplicated reports, 2,365,269 were cancer associated and 256,940 contained an ICI. Median age among cancer reports with observed age was 66 years (IQR, 56-75 years); 1,031,999 (43.6%) were female and 1,003,154 (42.4%) were male. Exposures: ICI exposure in any reported drug role, individual primary-suspect drugs, and checkpoint-pathway exposure. Main Outcomes and Measures: Reporting odds ratios (ORs), cross-organ adverse-event communities, adjusted primary-suspect drug x ICI interaction ORs for Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), interstitial nephritis, drug-induced liver injury (DILI), and vomiting (VOM), and accelerated failure-time model time ratios for documented onset. Results: Of 3001 eligible Preferred Terms in cancer-associated reports, 2091 differed at a false discovery rate (FDR) less than .05. Four cross-organ toxicity communities were identified. Of 138 eligible drug-phenotype pairs, 65 had FDR-significant interactions, including moxifloxacin-SJS/TEN amplification (interaction OR, 101.72; 95% CI, 39.11-264.55), enfortumab vedotin-SJS/TEN attenuation (interaction OR, 0.17; 95% CI, 0.13-0.23), and omeprazole-interstitial nephritis amplification (interaction OR, 10.35; 95% CI, 7.62-14.05). Among 60,324 reports contributing to temporal analyses, ICI exposure was associated with longer adjusted documented time to onset for 5 of 6 phenotypes (time ratios, 1.37-1.59) but not AGEP (time ratio, 0.99; 95% CI, 0.67-1.46). Temporal associations also differed across checkpoint pathways. Conclusions and Relevance: ICIs were associated with a structured cross-organ toxicity landscape, phenotype-specific modification of drug-associated adverse events, and distinct temporal patterns across checkpoint pathways. These findings support checkpoint blockade as a modifier of drug-associated toxicity and motivate longitudinal and mechanistic validation.

Objective: The Brief-cope questionnaire explore coping behavior. However, the underlying factor structure remains a subject of ongoing debate. Exploratory factor analyses (EFA) conducted across different populations have identified factor solutions ranging from two to fourteen factors. As of yet, the underlying factor structure of the Brief-cope has not been investigated in patients with seropositive rheumatoid arthritis (RA). Therefore, the aim of this study was to explore the underlying factor structure of the Brief-cope in a German population of seropositive RA. Methods: 216 outpatients with seropositive RA completed the Brief-cope. An EFA with principal axis factoring and Promax rotation was conducted. Results: EFA indicated a five-factor solution. The five-factor solution explained 51.95% of variance. The identified factors were: (1) problem-focused coping (Cronbach's = .851), (2) emotion-focused coping ( = .754), (3) maladaptive coping ( = .747), (4) religious coping ( = .851), and (5) substance-use coping ( = .869). Conclusion: A five-factor solution provided the most appropriate representation of the underlying factor structure of the Brief-cope in patients with seropositive RA. This factor structure may serve as a suitable basis for future analyses of Brief-cope data in comparable RA populations.

Background: Multiple sclerosis (MS) is a chronic, immune-mediated disease of the central nervous system marked by demyelination and neurodegeneration. Beyond physical symptoms, MS is often linked to clinically relevant sleep disturbances. The variability and unpredictability of symptoms and disease progression can also fuel fear of relapse (FoR), undermining well-being and potentially increasing morbidity through inflammatory processes. Understanding biopsychosocial risk factors, including childhood maltreatment (CM) and sleep, in relation to FoR remains an important gap in MS management and research. Methods: Data from N = 48 participants were collected via an online survey. We used the Pittsburgh Sleep Quality Index (PSQI), the Fear-of-Relapse Scale (FoR), and the Childhood Trauma Questionnaire (CTQ) to assess the variables of interest. In addition, time points of exposure to different CM subtypes were assessed. Linear regression analyses were conducted to examine associations within the proposed negative triad. Results: A significant negative association between overall sleep quality and FoR was observed. In the total cohort, the interaction between CM and sleep was not a significant predictor of FoR. However, exploratory analysis revealed a significant interaction between CM and sleep among male participants, whereas the same interaction was not significant among female participants. Conclusion: A history of CM and impaired sleep quality introduce new stressors in managing one's own illness that have received little attention to date. However, the present study found that these factors were at least partly influential on the FoR. The results underscore the translational need for additional support services to enhance prevention and personalized care.

Background: Patients receiving anti-TNF treatment for chronic inflammatory disease display impaired antibody responses, but it remains unclear how immune memory formation is affected. We evaluated antibody responses and memory B cells (Bmem) after COVID-19 booster vaccination in inflammatory bowel disease (IBD) patients receiving anti-TNF treatment. Methodology: Blood was sampled at baseline, 1, and 6 months after WH1/BA.5 bivalent or XBB.1.5 monovalent vaccination from 27 IBD patients receiving intravenous anti-TNF and 44 controls. Neutralizing antibodies were measured using an infectious virus assay. SARS-CoV-2 spike receptor binding domain (RBD)-specific serum IgG was quantified by ELISA, and RBD-specific Bmem were immunophenotyped by flow cytometry using recombinant proteins from ancestral, Omicron BA.1, BA.5, XBB.1.5, and JN.1 variants. Results: Serum IgG to vaccine RBD and neutralizing antibodies in patients increased pre to 1 month post-vaccination, but were lower than controls. Ancestral-, BA.5- and XBB.1.5-specific Bmem increased after vaccination but were significantly lower in patients than controls. Within RBD-specific Bmem, frequencies of recently activated CD21lo cells were increased after vaccination, and were higher in patients than controls. Fewer antigen-specific Bmem in patients expressed IgG4, and more expressed IgG3 or IgD following vaccination. Following vaccination, more RBD-specific Bmem recognized multiple viral variants. However, patients had fewer Bmem that could bind to subvariants than controls. Conclusion: Antibody and Bmem responses to COVID-19 booster vaccination in anti-TNF-treated IBD patients displayed reduced capacity, durability and cross-reactivity, suggesting impaired immune memory for protection against breakthrough infection. This supports the recommendation for annual booster vaccination to prevent severe disease and viral spread.

Background: Polymorphisms in the N-acetyltransferase 2 (NAT2) gene explain much of the interindividual variation in isoniazid (INH) metabolism and determine risk of toxicities. However, there is limited evidence to guide INH dose adjustment according to the NAT2 acetylator profile in weekly rifapentine-INH tuberculosis preventive therapy (TPT). Methods: In a prospective, multicenter, within-subject PK trial (NCT05413551), adults initiating 3HP in Brazil were assigned genotype-guided INH doses (slow: 5 mg/kg <=300 mg; intermediate: 15 mg/kg <=900 mg; rapid: 25 mg/kg <=1,500 mg) alongside a standard 900 mg flat dose on an alternate occasion. AUC0-24 and C24 were estimated from serial blood samples; a two-compartment Michaelis-Menten population PK model characterized NAT2 effects on clearance. Results: Among 228 participants, 47.4% (108/228) were intermediate, 43.4% (99/228) slow, and 9.2% (21/228) rapid acetylators. Genotype-guided dosing reduced AUC0-24 variability approximately two-fold versus standard dosing (CV 58.8% vs 76.8%) and increased exposure uniformity (median AUC0-24 27.2 [IQR 18.8-41.3] vs 43.2 [27.3-71.0] mg h/L). Among slow acetylators, C24 >0.15 ug/mL decreased from 27/42 (64%) with standard dosing to 1/42 (2%) with genotype-guided dosing (P<0.0001). In 104 participants with intensive PK sampling, rapid acetylators receiving guided doses had AUC0-24 similar to standard-dose intermediate acetylators (42.8 vs 39.5 mg h/L; P=.63). Monte Carlo simulations supported doses of 600, 900, and 1,200 mg for slow, intermediate, and rapid acetylators, respectively. Conclusions: NAT2-guided isoniazid dosing reduced variation in drug levels, averting very low and high AUC and C24. These findings inform genotype-stratified dosing of INH for TPT, which might reduce toxicities and improve outcomes.

Objectives Emergency department (ED) crowding is recognised as an important public health concern internationally, and is driven principally by exit block, the shortage of inpatient beds for patients requiring admission. This study aimed to evaluate whether a complex intervention targeting hospital occupancy improved ED patient flow, and quantified the change in attendances. Methods A controlled interrupted time series using weekly, publicly reported Public Health Scotland data from 1 January 2022 to 1 February 2026. The multi-component intervention focused on reducing hospital occupancy and included additional adult social care funding; engagement with regional social care providers; accelerated implementation of the Discharge without Delay programme; re-evaluation of whole-hospital escalation thresholds and response; resource and data supporting inpatient department reductions in length of stay; and additional investment in remote clinical assessment. The intervention commenced at a large tertiary ED on 01 February 2025. Primary outcomes were the proportions of attendances spending [&ge;]4, [&ge;]8 and [&ge;]12 hours in the ED. The secondary outcome was attendance volume. Segmented regression was fitted with a contemporaneous control series, seasonal terms and autoregressive moving average errors. Long waits were additionally illustrated as potentially avoided deaths. Results The analysis covered 161 pre-intervention and 52 post-intervention weeks. Relative to pre-intervention levels, the proportion of attendances waiting over 4 hours fell by 10.4% (95% CI 1.6 to 19.2%), by 16.4% (95%CI 1.3 to 31.5%) over 8 hours and by 24.3% (95%CI 2.6 to 46.1%) over 12 hours. Using established associations between long ED waits and excess mortality, by one-year the intervention was potentially associated with 54 fewer excess deaths (95%CI 19 to 93). Attendances rose by 3.8% (95%CI 1.3 to 6.4%) against the counterfactual. Conclusions A complex intervention targeting hospital occupancy was associated with a reduction in long ED waits despite rising attendances. Interventions addressing hospital occupancy can meaningfully improve ED crowding.

Vaccine responses vary across individuals due to differences in ageing and health status. Using transcriptomic profiling, we analyzed early gene expression profiles after influenza (QIV) followed by pneumococcal (PCV13) vaccination in 148 participants spanning young, middle-aged, and older adults. The two vaccines induced distinct immune signatures: QIV elicited innate and interferon immune activation, while PCV13 triggered inflammation-based responses. Older adults showed weaker but similar transcriptomic profiles compared to young adults. Among older adults, frailty, in addition to age, was strongly associated with reduced innate responses. In addition, we identified associations between early-stage transcriptomic profiles and later-stage antibody responses for QIV; however, no such associations were observed for PCV13. Importantly, observed group differences arose not from altered immune modules but from differences in the magnitude of gene expression, paving the way for immune-boosting interventions to enhance early gene expression in at-risk populations.

Introduction Miltefosine is the only approved oral antileishmanial agent, but its use in women of childbearing potential (WOCBP) is restricted due to preclinical teratogenicity. Current labeling recommends contraception during treatment and for at least five months thereafter, based solely on its long terminal elimination half-life. This study re-evaluated the required contraceptive duration using an exposure margin-based approach. Methods Virtual populations were generated from anthropometric data of 382 Indian, 4,462 Eastern African, and 4,019 Brazilian WOCBP with leishmaniasis. Published population pharmacokinetic models were used to simulate miltefosine exposure following 14-42-day regimens for visceral leishmaniasis (VL), post-kala-azar dermal leishmaniasis (PKDL), and cutaneous leishmaniasis (CL). A developmental safety exposure threshold was derived from the rat no-observed-adverse-effect level (0.6 mg/kg/day for 10 days) and adjusted using a 10-fold safety margin. Contraceptive durations resulting in median residual post-contraception exposure (AUCEOC-{infty}) below this threshold were considered supportive of contraceptive discontinuation. Results The developmental safety exposure threshold was estimated at 2.5 mg{middle dot}day/L. Despite pharmacokinetic differences across geographical regions and disease manifestations, required minimum contraceptive durations were consistent: three months from treatment initiation for the 14-day regimen, four months for 21- and 28-day regimens, and five months for the 42-day regimen. For the 14-day regimen, a single dose of a long-acting injectable contraceptive administered at treatment initiation would provide sufficient coverage. Conclusion An exposure margin-based approach supports shorter contraceptive durations than current recommendations. For the 14-day VL regimen, three months of contraception may provide a practical alternative to current labeling.

Purpose: Lung cancer screening (LCS) with low-dose computed tomography (LDCT) reduces lung cancer mortality, yet screening participation remains low. We evaluated whether a brief informational video nudge delivered immediately before a scheduled clinical encounter increased LCS ordering and baseline LCS completion. Patients and Methods: We conducted a randomized feasibility trial within Kaiser Permanente Colorado from March through October 2025. LCS-eligible patients with an upcoming primary care or pulmonology appointment were assigned to intervention or usual care based on birth month. Intervention patients were split into two group, a group who received the LCS informational video nudge via text message within 24 hours of an eligible appointment; and second group who received the text plus a QR code video link during appointment rooming. Outcomes included LCS orders, baseline LCS-LDCT completion, and video engagement. Multivariable logistic regression was used to evaluate factors associated with LCS ordering. Results: Among 1,093 patients, 549 were assigned to intervention and 544 to usual care. Intervention patients were more likely to receive an LCS order within 1 day of their appointment (22.6% vs 16.4%; p=.010) and any time during follow-up (32.6% vs 24.1%; p=.002). Baseline LCS-LDCT completion was 51% higher in the intervention group, although the difference was not statistically significant (8.6% vs 5.7%; p=.078). Among the intervention group, 93 individuals (17%) viewed the video, generating 114 total views, and viewers watched an average of 79% of the video. Most views (82.5%) occurred through text-message delivery rather than QR codes. Conclusion: A brief, low-burden LCS informational video delivered immediately before a clinical encounter and integrated into existing workflows significantly increased LCS ordering and was associated with higher screening completion. Timely, scalable digital nudges may provide an effective strategy for improving LCS participation. Based on the observed effectiveness, feasibility, and efficiency of the intervention, KPCO incorporated the behavioral nudge into standard clinical care in February 2026.

Background: Refractory and macrolide-resistant Mycoplasma pneumoniae pneumonia (MPP) has emerged as a major challenge in pediatric respiratory medicine, amplified by the post-2023 resurgence. However, a systematic overview of the research landscape specific to treatment-refractory and drugresistant disease in children remains lacking. Methods: Research articles and reviews on pediatric refractory or macrolide-resistant MPP published between 2000 and 2025 were retrieved from OpenAlex using Boolean searches. After screening, 2,286 records were quantitatively analyzed for annual output, contributing countries/institutions, thematic clusters, and citation-burst dynamics using Python. Results: Annual publications grew exponentially, with a pronounced surge after 2023 (n=378 in 2025). China produced the highest volume (45.1%) but recorded fewer citations per publication than the US, Japan, and Canada. The literature resolved into four clusters: macrolide resistance/molecular basis, epidemiology, etiology/co-infection, and refractory disease management. Burst analysis showed an evolution from earlier fronts like 23S rRNA mutations and azithromycin to recent emerging trends like pandemic-related co-circulation, genotype surveillance, and co-infection. Conclusions: Research on pediatric refractory and resistant MPP is expanding rapidly, shifting in emphasis from etiologic descriptions toward resistance mechanisms and clinical management. Standardizing the treatment of macrolide-unresponsive disease and post-pandemic epidemiological surveillance represent the principal directions for future work. Keywords: Mycoplasma pneumoniae; children; macrolide resistance; refractory pneumonia; bibliometric analysis; research trends

Introduction: Continuous glucose monitoring (CGM) offers an advancement over traditional self-monitoring of blood glucose (SMBG) for people living with type 1 diabetes (T1D). However, evidence on the acceptability and feasibility of different CGM use cases in African populations remains limited. Methods: This was a pragmatic three-arm, randomised controlled trial on CGM conducted among people living with T1D in three public healthcare clinics in South Africa. Participants were assigned to Arm 1 (continuous CGM), Arm 2 (periodic CGM), or Arm 3 (SMBG). Diabetes education was provided at all study visits. Feasibility was assessed by adherence to CGM use and through the Glucose Monitoring Satisfaction Survey (GMSS). Diabetes distress was measured by the Diabetes Distress Scale (DDS), health-related quality of life (HRQoL) by the EQ-5D scales, and acceptability using the Theoretical Framework of Acceptability (TFA). Surveys were collected on paper and transferred to OpenClinica. Analyses were performed in R. The trial was registered in the Clinical Trials Registry (NCT05944718) on July 13, 2023. Results: A total of 83 participants were included in Arm 1, 85 in Arm 2, and 80 in Arm 3. CGM mean active time was 55% in Arm 1 versus 69% in Arm 2. The proportion of participants meeting the [&ge;]70% active time threshold was higher in Arm 2 (52%) than in Arm 1 (34%). Diabetes' distress declined across arms during the intervention period, with no significant difference between arms; distress increased slightly six months post-intervention but remained below baseline. At 6 months, glucose monitoring satisfaction was significantly higher in both CGM arms than in the SMBG arm, and satisfaction increased over time in CGM arms. Health-related quality of life remained stable across arms during the intervention period with no significant difference between arms. High acceptability was observed in both CGM arms, with higher ratings in the periodic arm. Conclusions: CGM was acceptable to people living with type 1 diabetes and feasible to use in public-sector clinics in South Africa, with high acceptability under continuous and periodic use. Health-related quality of life remained stable across arms, and diabetes-related distress declined, during the intervention period, across arms. Glucose monitoring satisfaction rose significantly in both CGM arms compared to SMBG. Periodic CGM might be a promising and potentially more scalable option than continuous use for public-sector care.

Background and Objectives: Recurrence following burr-hole drainage of chronic subdural haematoma (cSDH) occurs in 10-25% of cases, sustained by neovascularisation of the subdural neomembrane supplied by the middle meningeal artery (MMA). MMA embolisation reduces recurrence; whether incidental burr-hole intersection of MMA branches during drainage confers similar benefit is unknown. Methods: We performed a multicentre retrospective cohort study of consecutive adults undergoing burr-hole drainage for cSDH at two UK tertiary neurosurgical centres. Postoperative thin-slice CT was used to classify burr-hole intersection of the underlying MMA groove (no hit, distal-branch hit or main-branch hit) and measure perpendicular burr-hole-to-MMA-groove distance. Co-primary outcomes were radiological recurrence and recurrence requiring intervention. Patient-clustered multivariable logistic regression adjusted for prespecified clinical covariates and treating site. Results: 227 patients (284 operated hemispheres) were included. Radiological recurrence decreased from 34.4% with no branch hit to 22.9% with main-branch intersection, with the gradient confined predominantly to unilateral cSDH. Main-branch intersection was associated with lower adjusted odds of radiological recurrence in unilateral cSDH (adjusted OR 0.30, 95% CI 0.11- 0.81; P = .018), with a similar but non-significant association in the overall cohort (adjusted OR 0.53, 95% CI 0.26-1.07; P = .075). Burr-hole-to-MMA-groove distance demonstrated a more consistent association: in the overall cohort, each 5-mm increase independently increased the odds of radiological recurrence (adjusted OR 1.38, 95% CI 1.04-1.82; P = .025). In unilateral cSDH, each 5-mm increase was independently associated with both radiological recurrence (adjusted OR 1.45, 95% CI 1.03-2.04; P = .034) and recurrence requiring intervention (adjusted OR 1.52, 95% CI 1.05-2.20; P = .027). Conclusion: Main-branch intersection of the middle meningeal artery during routine burr-hole surgery is associated with lower recurrence of unilateral cSDH, while the accompanying burr-hole-to-MMA-groove distance gradient provides biologically plausible support for a dose-response relationship. Together, these findings provide mechanistic rationale for prospective evaluation of intentional neuronavigation-guided MMA targeting (BURR-MMA; NCT07549893).

Disseminating study results to participants is an ethical responsibility for researchers but remains uncommon in low- and middle-income countries, and participants preferences for receiving study results are poorly understood. This study examined study result dissemination preferences among pregnant women in a phase III malaria prevention trial in Papua New Guinea (PNG). Participants completed an interviewer-administered questionnaire (survey) assessing their interest in and motivation for receiving trial results and preferences for dissemination methods and content. Associations between participants characteristics and dissemination preferences were explored using multivariable logistic regression analysis. Of 1172 trial participants, 96.0% (1125/1172) completed the survey, and of these 99.6% (1121/1125) wanted to learn about the trial results. The main motivation factors driving participants interest were an acknowledgment of their contribution to research (51.7%; n=579) and a better understanding of the study (45.0%; n=505). Most participants (78.9%; n=884) wanted to learn about the trial findings through written summary and a group meeting with other participants at the nearest clinic (31.1%, n=349). Multivariable regression analysis indicated that participants from rural/peri-urban clinics were more likely to choose non-electronic media dissemination approaches such as a group meeting as compared to urban-dwelling participants. Frequently selected items (>50% of participants) for content included information regarding good results of the study, purpose of the study, medical treatment advances, results specific to me, and how study was conducted. There was heterogenicity in the preference for dissemination content: compared to urban clinics rural clinics are less likely to want to learn about how and why study was conducted and medical and scientific advances. Overall, the majority wanted to learn about trial results, highlighting the importance of integrating dissemination into research activities in PNG. Variation in preferences for mode and content of dissemination between study clinics suggests that dissemination activities could be tailored to local context and preferences.

Background: Systematic reviews of clinical prediction models increasingly include studies using artificial intelligence (AI) and machine learning (ML) methods alongside traditional multivariable regression approaches. A previously published Excel tool enabled standardised data extraction using the CHARMS checklist and risk of bias assessment using PROBAST. The recent publication of the PROBAST+AI framework, which distinguishes the assessment of model development quality from the assessment of model evaluation risk of bias and assesses applicability in both parts, necessitates an updated digital instrument applicable across prediction modelling methods. Methods: We updated an open-access Excel tool to incorporate the full PROBAST+AI framework. The updated template incorporates structural separation between assessment of model development quality and model evaluation risk of bias, with applicability assessed in both parts. It also incorporates updated signalling questions, including those addressing methodological issues particularly relevant to AI/ML, and automates the generation of summary tables and graphical displays. Results: The updated tool (CHARMS & PROBAST+AI Template) contains 11 worksheets and supports data extraction and appraisal for up to 30 prediction models. Dedicated, linked worksheets enable separate assessment of model development and model evaluation, with Domain 4 distinguishing among Apparent, Internal, and External evaluation settings. Key updates include dedicated assessments for predictor pre-processing, class imbalance handling and recalibration, data leakage prevention, and replication of the full model development pipeline within resampling procedures. Automated sheets dynamically format tables and summary charts covering PROBAST+AI parts. Conclusions: The CHARMS & PROBAST+AI Excel template provides a standardised, user-friendly, and rigorous digital framework for systematic reviewers appraising traditional statistical and AI-driven clinical prediction models.

Background: Fibrosis, characterised by excessive accumulation of collagen type I (COL1), is a common feature of chronic diseases, including liver diseases (LDs), chronic kidney disease (CKD) and heart failure (HF). COL1 degradation products can be detected in urine by proteomics/ peptidomics analyses and may serve as non-invasive biomarkers of fibrosis. We aimed to identify a common molecular signature of fibrosis across these diseases that may ultimately guide interventions to slow disease progression and prevent organ damage. Methods: Using capillary electrophoresis coupled to mass spectrometry (CE-MS), naturally occurring COL1 degradation products (peptides) in the urine of patients with fibrotic disease, LDs (n=127), CKD (n=263) or HF (n=187), were investigated and compared with the same number of matched controls. Disease-associated COL1 peptides were identified separately for each condition, and peptides showing consistent associations across the three diseases were selected to define a common fibrosis signature. A support vector machine model based on the selected peptides was developed and validated in independent cohorts of patients with LDs (n=110), CKD (n=93), HF (n=32) and controls (n=643). Results: We identified a common fibrotic signature consisting of 50 COL1 degradation products, mainly downregulated in fibrosis. A model based on these peptides achieved a strong performance, with an area under the receiver operating characteristic curve (AUC) of 0.935 (95% confidence interval (CI) 0.917-0.953, p<0.0001) in an external validation cohort comprising pooled disease groups (LDs, CKD, and HF) and controls. Performance was maintained in LDs, CKD and HF, with AUCs of 0.917 (95% CI 0.890-0.944, p<0.0001), 0.951 (95% CI 0.931-0.971, p<0.0001) and 0.950 (95% CI 0.903-0.997, p<0.0001), respectively. The model scores were significantly associated with fibrosis stage in LDs (p=0.0097) and with interstitial fibrosis and tubular atrophy in CKD (p=0.045). Conclusion: A model of urinary COL1 peptides captures a shared collagen degradation signature across organs and diseases, enabling the non-invasive assessment of fibrosis irrespective of its origin. As these peptides exclusively reflect collagen degradation, the findings suggest impaired collagen degradation as a driver in fibrosis. Future clinical studies are warranted to evaluate the utility of this model for early fibrosis detection and earlier implementation of anti-fibrotic interventions.

The 17th Ebola outbreak in the Democratic Republic of the Congo, announced on 15 May 2026, was attributed to Bundibugyo ebolavirus (BDBV). Although case isolation is the main control strategy, its effectiveness is compromised when patients escape isolation facilities before recovery. Between 14 May and 17 June 2026, 175 individuals reportedly left isolation facilities without formal discharge across Ituri Province. We assessed how this "isolation leakage" affects community transmission. We refined the SEIHFR framework to distinguish undetected community infections, detected but not-yet-isolated cases, isolated individuals, leakage, funeral-associated transmission, and removals. Using Bayesian inference, we fitted the model to daily Ituri surveillance data, escapee counts, and isolation census records. We estimated the leakage rate, reporting and detection probabilities, and the transmission rate, while fixing other parameters based on the BDBV literature. The model reproduced confirmed cases, deaths, discharges, and escapees. We estimated R_0=3.67 (95% HDI: 2.0-5.7), a leakage rate of {rho} {approx} 0.034 day^-1 (0.022-0.051), and high contact-tracing-driven detection (p_d {approx} 0.91-0.99). Leakage increased the detection-dependent reproduction number [R](p_d) from approximately 3.2 to above 5. Eliminating leakage reduced cumulative infections by about one-third, from 1,120 to 764, while the minimum detection level required for control increased from p_d [&ge;] 0.73 without leakage to p_d [&ge;] 0.87 at the fitted leakage rate. Shortening time to isolation prevented the most infections (73.4%; 59-84), followed by reducing leakage (29.7%; 14-52) and re-isolating escapees (12.6%; 6-24). Delaying leakage reduction until week 4 reduced its benefit from about 27% to below 2%. Isolation leakage represents a major transmission pathway that has until now gone largely unmeasured. While rapid initiation of isolation is highly beneficial, it cannot compensate for permeable isolation; therefore, early, community-driven efforts to control leakage, embedded within a multilayered response, are critical.

Objective: To determine whether paradoxical relief, feeling unusually better after a seizure compared to before it, is more common after functional/dissociative seizures (FDS) than epileptic seizures (ES), quantify its diagnostic accuracy, and explore its relationship with preictal symptoms. Methods: Consecutive patients admitted to a tertiary epilepsy unit for prolonged inpatient EEG monitoring underwent a structured clinical interview on admission, before final multidisciplinary diagnostic classification. Preictal dissociative and autonomic/somatic symptom burden was assessed using items adapted from established questionnaires. Diagnostic classification incorporated clinical history, seizure semiology, video electroencephalography findings, and collateral information. Patients with dual or indeterminate diagnoses were excluded. Associations with paradoxical relief were examined using logistic regression, followed by an exploratory mediation analysis. Results: Of 176 patients assessed, 66 with FDS and 65 with ES were included. Paradoxical relief was reported by 46/66 patients with FDS (69.7%) and 10/65 with ES (15.4%; unadjusted odds ratio [OR] 12.65, 95% confidence interval [CI] 5.57 to 31.09). As a diagnostic signal for FDS, paradoxical relief had 69.7% sensitivity (95% CI 57.1 to 80.4), 84.6% specificity (95% CI 73.5 to 92.4), a positive likelihood ratio of 4.53 (2.51 to 8.19), and a negative likelihood ratio of 0.36 (0.24 to 0.52). FDS diagnosis remained independently associated with paradoxical relief after adjustment (OR 10.59, 95% CI 3.42 to 38.06). In a parallel mediation analysis, dissociative symptom burden showed a significant indirect effect, accounting for 19.5% of the association between diagnostic group and relief, whereas the indirect effect through somatic/autonomic symptom burden was not significant. Significance: Paradoxical relief is substantially more common after FDS than ES and may provide a simple, clinically useful diagnostic signal. Its absence does not exclude FDS, and the finding requires external validation. The association with dissociative symptoms is exploratory and supports prospective investigation of whether relief reflects transient resolution of a disturbed, disembodied preictal state.

Background: Cancer is a growing public health challenge in Ghana, with 27,385 new cases and 17,944 deaths recorded in 2022. Ghana developed a National Cancer Control Strategy (NCCS) in 2011 to guide prevention, early detection, treatment, and palliative care. The strategy expired in 2016 and has not been formally evaluated or renewed, leaving cancer control efforts without a guiding policy framework for nearly a decade. This study examined how the strategy was implemented, what barriers were encountered and what stakeholders recommend for a strengthened national cancer response. Methods: We conducted a qualitative descriptive study using semi-structured key informant interviews. Fifteen participants were recruited through purposive sampling, supplemented by snowball referrals, representing three groups: Ministry of Health policymakers, frontline healthcare providers and representatives of cancer-focused non-governmental organisations. Data were collected between June and September 2025 and analysed using Braun and Clarke's six-phase thematic analysis framework, guided deductively by the WHO Health Systems Building Blocks framework Results: Three themes emerged: NCCS interventions and systems implemented, capturing progress in cancer awareness, HPV vaccination and pilot screening programmes alongside persistent geographic and financial inequities in access; barriers to implementation, including inadequate financing, infrastructure and workforce shortages, the absence of a national cancer registry and governance failures, among them the finding that no frontline healthcare provider interviewed had any awareness of the NCCS; and recommended implementation strategies, including co-production of a renewed strategy, establishment of a dedicated National Cancer Control Programme, expanded health insurance coverage and decentralisation of oncology services. Conclusion: The NCCS was not operationally embedded in the health system. The evidence points to failures in policy dissemination as a constraint that precedes resource constraints. Addressing Ghana's rising cancer burden requires renewed political commitment, co-produced governance structures and accountability mechanisms. These findings have relevance for other low- and middle-income country settings facing similar challenges.