Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
Showing 11 appraisals
Gut
Simvastatin in the prevention of recurrent pancreatitis: a triple-blinded randomised clinical trial (the SIMBA trial)
BACKGROUND: Recurrent acute pancreatitis (RAP) or acute-on-chronic flares in chronic pancreatitis (CP) have limited preventive options beyond addressing the underlying aetiology. Statins, due to their anti-inflammatory properties, have been proposed as a potential prophylactic treatment. OBJECTIVE: We aimed to evaluate whether simvastatin could reduce the recurrence of pancreatitis. DESIGN: At 23 centres, we conducted a triple-blind, randomised, controlled, superiority trial enrolling patients with at least two episodes of RAP or CP flares in the previous 12 months. Participants were randomly assigned to receive simvastatin or placebo for 1 year. The primary endpoint was the recurrence of pancreatitis. The target sample size was 144 patients; however, an interim analysis was planned in the event of slow recruitment. RESULTS: A total of 85 patients (42.1% women) were included in the interim analysis. In the intention-to-treat analysis, no significant differences were observed regarding recurrence: 46.2% simvastatin versus 44.4% placebo; OR 1.07, 95% CI 0.43 to 2.66; p=0.88, or time to recurrence. No statistically significant differences were observed in recurrence in per-protocol analysis (35.5% simvastatin vs 41.9% placebo; OR 0.76, 95% CI 0.27 to 2.12; p=0.60). Development of diabetes mellitus was more frequent in the simvastatin group (4 vs 0 patients; OR not calculable, p=0.04). CONCLUSION: This trial, evaluating simvastatin versus placebo for the prevention of pancreatitis, did not demonstrate a reduction in recurrence rate, although results might be underpowered due to early termination. The relationship between statins in these patients and new-onset diabetes requires further investigation. TRIAL REGISTRATION NUMBER: NCT04021498.
14 May 2026
Read appraisal →Lancet (London, England)
Efficacy and safety of cemdisiran siRNA in myasthenia gravis (NIMBLE): a double-blind, randomised, placebo-controlled, phase 3 trial
BACKGROUND: Autoantibody-mediated complement activation drives pathology in acetylcholine receptor (AChR) antibody-positive generalised myasthenia gravis. Newer targeted therapies lower overall antibody concentrations or inhibit complement activity. We aimed to evaluate an siRNA (cemdisiran) targeting complement component 5 (C5) as monotherapy and in combination with a C5 antibody (pozelimab) in generalised myasthenia gravis. METHODS: NIMBLE is a randomised, double-blind, placebo-controlled, phase 3 trial conducted at 86 centres in 13 countries. We enrolled patients aged 18 years or older with a diagnosis of generalised myasthenia gravis, positive serology for anti-AChR or anti-LRP4 antibodies, and a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of 6 or greater. Patients were randomly allocated to receive cemdisiran monotherapy (600 mg every 12 weeks; cemdisiran group), pozelimab monotherapy (200 mg every 4 weeks; pozelimab group), combined cemdisiran (200 mg every 4 weeks) and pozelimab (200 mg every 4 weeks; combination group), or placebo, all administered subcutaneously, during a 24-week double-blind treatment period. The primary endpoint was change from baseline in MG-ADL scores at week 24, assessed in the modified intention-to-treat (mITT) primary analysis set (the first 245 randomly allocated patients who received any dose of study treatment and had at least one post-baseline assessment). A prespecified hierarchal statistical testing strategy was used; multiplicity was controlled for comparisons of cemdisiran versus placebo and combination versus placebo (pozelimab was not statistically tested against placebo and was used only to assess the contribution of components to the combination treatment). Safety was mainly assessed by recording of treatment-emergent adverse events in all patients who received any dose of study treatment. This study is registered with ClinicalTrials.gov (NCT05070858); the current status is active, not recruiting. FINDINGS: Between Jan 20, 2022 and July 18, 2025, 390 participants were screened and, as of the data cut-off presented in this report (July 8, 2025), 284 were randomly allocated to the cemdisiran group (79 [28%] patients), pozelimab group (50 [18%]), combination group (80 [28%]), and placebo group (75 [26%]). Of 277 patients who received any study treatment, 263 (95%) completed the double-blind treatment period. In the mITT primary analysis set, at week 24, the least-squares mean change from baseline in MG-ADL total score was -4·5 (SE 0·4) in the cemdisiran group (n=64), -4·0 (0·4) in the combination group (n=67), and -2·2 (0·5) in the placebo group (n=59). Placebo-adjusted least-squares mean differences in MG-ADL score at week 24 were -2·3 (SE 0·7; 95% CI -3·6 to -1·0; p=0·0005) in the cemdisiran group and -1·7 (0·7; -3·0 to -0·4; p=0·0086) in the combination group. The proportion of participants with at least one adverse event during the double-blind treatment period was 54 (69%) of 78 in the cemdisiran group, 65 (81%) of 80 in the combination group, 40 (82%) of 49 in the pozelimab group, and 54 (77%) of 70 in the placebo group. The most common adverse event in the cemdisiran group was upper respiratory tract infection (nine [12%] of 78 patients), which occurred at a similar incidence in the placebo group (eight [11%] of 70). No serious or meningococcal infections occurred in the cemdisiran group. Adverse events leading to treatment discontinuation occurred in two participants (3%) in the placebo group and one participant (2%) in the pozelimab group. No deaths occurred during the double-blind treatment period. Two deaths occurred after the double-blind treatment period, one of which was assessed as treatment-related by the investigator but not treatment-related by the sponsor. INTERPRETATION: Cemdisiran monotherapy and combination therapy were effective in the treatment of generalised myasthenia gravis, and were generally well tolerated. Subcutaneous dosing of cemdisiran, administered every 3 months, could provide a convenient treatment approach for generalised myasthenia gravis. FUNDING: Regeneron Pharmaceuticals.
10 May 2026
Read appraisal →EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology
Impact of renal function on edoxaban antithrombotic therapy in patients with atrial fibrillation and stable coronary artery disease: a prespecified analysis of the EPIC-CAD trial
BACKGROUND: Renal function is a critical factor of ischaemic and bleeding risks in patients with atrial fibrillation (AF) receiving antithrombotic therapy. AIMS: This study aimed to evaluate the impact of renal dysfunction in patients with AF and stable coronary artery disease (CAD) undergoing antithrombotic therapy. METHODS: The Edoxaban Versus Edoxaban With antiPlatelet Agent In Patients With Atrial Fibrillation and Chronic Stable Coronary Artery Disease (EPIC-CAD) trial randomised patients to edoxaban monotherapy or dual antithrombotic therapy (edoxaban plus a single antiplatelet agent). In this prespecified analysis, patients were stratified by creatinine clearance into low (<50 mL/min) or high (≥50 mL/min) groups according to edoxaban dose-reduction criteria. The primary endpoint was net adverse clinical events (NACE: death from any cause, myocardial infarction, stroke, systemic embolism, urgent revascularisation, or major/clinically relevant non-major bleeding) at 12 months. RESULTS: Of 1,040 randomised patients, 252 (24.2%) had low creatinine clearance; these patients were older and had more comorbidities compared with the 788 patients (75.8%) with high creatinine clearance. Patients with low creatinine clearance experienced higher risks of NACE (hazard ratio [HR] 1.72, 95% confidence interval [CI]: 1.19-2.49; p=0.004), ischaemic events (HR 2.70, 95% CI: 1.09-6.70; p=0.032), and bleeding (HR 1.54, 95% CI: 1.01-2.34; p=0.046). At 12 months, edoxaban monotherapy reduced NACE compared with dual therapy in both the low (12.1% vs 21.7%, HR 0.52, 95% CI: 0.28-0.98; p=0.042) and high creatinine clearance groups (5.2% vs 14.5%, HR 0.40, 95% CI: 0.25-0.65; p<0.001), with no interaction (p for interaction=0.53). CONCLUSIONS: In patients with AF and stable CAD, edoxaban monotherapy led to a lower risk of primary NACE than dual antithrombotic therapy, regardless of renal function. (ClinicalTrials.gov: NCT03718559).
21 Apr 2026
Read appraisal →Medicine
Drug-induced neutropenia: A comprehensive pharmacovigilance study of the FAERS database.
Drug-induced neutropenia (DIN) deserves both clinicians' and researchers' attention for the serious clinical consequences. This study aimed to conduct an exploratory analysis of DIN reports in the United States Food and Drug Administration Adverse Event Reporting System database to identify drugs associated with neutropenia. A disproportionality analysis of DIN was conducted using reports submitted to the United States Food and Drug Administration Adverse Event Reporting System from the first quarter of 2004 to the fourth quarter of 2024. Both the reporting odds ratio algorithms and the information component were applied to identify an association between target drugs and DIN events. A total of 223,736 DIN cases were found, and 254 drugs were identified as potentially associated with neutropenia. The top-ranked drug categories were "monoclonal antibodies and antibody-drug conjugates," "other antineoplastic agents," "protein kinase inhibitors," "direct-acting antivirals," "antimetabolites," "alkylating agents," and "immunosuppressants." The top 5 drugs ranked by number of cases were clozapine, lenalidomide, rituximab, palbociclib, and carboplatin. The top 5 drugs ranked by reporting odds ratio signal strength were calcium levofolinate, vinorelbine, gemtuzumab ozogamicin, fludarabine, and daunorubicin. This comprehensive pharmacovigilance study identified drugs potentially associated with neutropenia, which can help clinicians and researchers further understand DIN.
20 Apr 2026
Read appraisal →The New England journal of medicine
Ianalumab plus Eltrombopag in Immune Thrombocytopenia
BACKGROUND: Current second-line treatments for immune thrombocytopenia (ITP) require long-term administration. Ianalumab, a monoclonal antibody targeting B cells, is being assessed as a short-course second-line therapy in ITP. METHODS: In this phase 3, randomized, double-blind trial, we assigned, in a 1:1:1 ratio, adults with primary ITP and an insufficient response or a relapse after first-line glucocorticoid therapy to receive ianalumab at a dose of 9 mg or 3 mg per kilogram of body weight or placebo once monthly for 4 months. Eltrombopag, an oral thrombopoietin-receptor agonist, was administered once daily in each group according to local prescribing information; the dose was tapered until discontinuation by the end of week 24 in eligible patients. The primary end point was freedom from treatment failure, as determined in a time-to-event analysis, with treatment failure defined by a platelet count of less than 30×109 per liter more than 8 weeks after randomization, initiation of rescue therapy more than 8 weeks after randomization, initiation of new ITP therapy, inability to taper or discontinue eltrombopag because of an inadequate platelet count, or death from any cause, whichever occurred first. The key secondary end point was a stable response at 6 months, defined by a platelet count of at least 50×109 per liter in at least 75% of the measurements between weeks 19 and 25 without use of rescue therapy or new ITP therapy. Safety was assessed. RESULTS: A total of 152 patients underwent randomization: 50 to the 9-mg ianalumab group, 51 to the 3-mg ianalumab group, and 51 to the placebo group. The estimated probability of being free from treatment failure at 12 months was 54% (95% confidence interval [CI], 39 to 67) in the 9-mg group, 51% (95% CI, 36 to 64) in the 3-mg group, and 30% (95% CI, 18 to 43) in the placebo group. The time to treatment failure was significantly longer with ianalumab plus eltrombopag than with placebo plus eltrombopag; the estimated hazard ratio for treatment failure (ianalumab vs. placebo) was 0.55 (P = 0.04) in the 9-mg group and 0.58 (P = 0.045) in the 3-mg group. The percentage of patients with a stable response at 6 months was significantly higher in the 9-mg group than in the placebo group (62% vs. 39%; P = 0.045). The overall frequency of adverse events during the treatment period was generally similar in the three groups. The frequency of serious adverse events was 16% in the 9-mg group, 6% in the 3-mg group, and 4% in the placebo group. CONCLUSIONS: Ianalumab plus eltrombopag led to a longer time to treatment failure than placebo plus eltrombopag. (Funded by Novartis; VAYHIT2 ClinicalTrials.gov number, NCT05653219.).
16 Apr 2026
Read appraisal →Medicine
Comparative evaluation of human T lymphocytes in HIV patients treated with lamivudine + zidovudine combined with nevirapine versus efavirenz
This study aimed to explore the efficacy of lamivudine + zidovudine plus nevirapine and efavirenz in the treatment hf human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS). A total of 100 patients with HIV/AIDS admitted to our hospital from June 2021 to September 2024 were selected and randomly assigned into nevirapine and efavirenz groups (n = 50 per group). The nevirapine group was treated with lamidudine plus zidovudine combined with nevirapine, and the efavirenz group was treated with lamidudine plus zidovudine plus efavirenz. The primary outcomes measured were the changes of lymphocyte count and adverse effects after 3 months of treatment. There was no statistical difference in baseline information between the 2 groups. After treatment, CD3 + and CD4 + levels were higher in the nevirapine group than in the efavirenz group (P <.05, 95% CI: 45.2-98.7 for CD3 + and 32.8-76.4 for CD4+), and CD8 + levels were lower in the nevirapine group than in the efavirenz group (P <.05); the overall incidence of adverse effects in the nevavirapine group was significantly lower than that in the efavirenz group (P <.05). In HIV/AIDS patients, treatment with lamivudine + zidovudine combined with nevirapine resulted in significantly improved CD4 + T cell counts, enhanced immune function, and fewer adverse reactions compared to treatment with lamivudine + zidovudine plus efavirenz, suggesting superior clinical value of the nevirapine-containing regimen.
12 Apr 2026
Read appraisal →BMJ open respiratory research
What is the evidence for virtual wards or hospital-at-home care pathways for exacerbations of chronic obstructive pulmonary disease? A systematic review and meta-analysis.
OBJECTIVES: Given increasing interest in admission avoidance, we evaluated the evidence to support virtual wards (VW) and hospital at home (HaH) models of care during exacerbations of chronic obstructive pulmonary disease (ECOPD). DESIGN: A systematic review and meta-analysis. A comprehensive search of MEDLINE (1946 to March 2024), Embase (1974 to March 2024) and CENTRAL (searched 22 March 2024) was conducted. Risk of bias and a random effects meta-analysis were performed. POPULATION: Adults with an ECOPD presenting to the hospital or who require hospital-led care. INTERVENTIONS: VW: defined as assessments and interventions delivered remotely or HaH (defined as assessments and interventions delivered by healthcare professionals in patient's homes) care pathways, compared with hospital admission. PRIMARY AND SECONDARY OBJECTIVES: Safety (mortality rate of all causes, in-patient, 7 days and 30 days) and readmission rate in 7 and 30 days. Length of stay in hospital and changes in pulmonary function tests. RESULTS: One study assessed VWs (reported in two publications) and 10 assessed HaH. There were no changes in survival or short-term readmission rates attributable to the interventions and no evidence that VW or HaH care pathways reduced the total time a patient spent under hospital-led care, whether at home or in the hospital. CONCLUSIONS: More evidence is needed to support the widespread roll-out of HaH and especially VW pathways for ECOPD. PROSPERO REGISTRATION NUMBER: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024517565.
12 Apr 2026
Read appraisal →Neurology
Efficacy of Pyridostigmine in Myasthenia Gravis: A Randomized, Double-Blind, Placebo-Controlled Crossover Trial
BACKGROUND AND OBJECTIVES: Pyridostigmine, an acetylcholinesterase inhibitor, is a symptomatic drug approved for the treatment of myasthenia gravis (MG), but no randomized controlled trials substantiate its widespread use. We aimed to assess the efficacy and cost utility of pyridostigmine in patients with anti-acetylcholine receptor-positive MG (AChR MG). METHODS: A randomized, double-blind, placebo-controlled crossover trial was conducted at Leiden University Medical Center, a tertiary center for the treatment of MG in the Netherlands. Main eligibility criteria were current use of pyridostigmine and a stable dose of other MG treatments. Participants were assigned to a sequence of 2 treatment periods for 5 days separated by a 2-day washout, in which patients either first received placebo and then pyridostigmine, or vice versa. Pyridostigmine dosing matched each participant's prestudy regimen. The primary outcome was change in the Myasthenia Gravis Impairment Index (MGII) score. Secondary efficacy outcome measures included the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale, the Quantitative Myasthenia Gravis (QMG) score, and the revised 15-item Myasthenia Gravis Quality of Life (MG-QOL15r) questionnaire. For the post hoc cost-utility analysis, a mathematical model was developed to translate the observed study results into long-term annual effect on societal costs and quality-adjusted life years (QALYs). RESULTS: A total of 19 patients (median age 59 years, 58% female) were recruited between March 23, 2023, and February 21, 2024. The estimated mean difference in the MGII score between pyridostigmine and placebo interventions was 5.3 (95% CI 1.9-8.7, p = 0.004). Secondary efficacy outcome measures showed estimated mean differences of 1.4 (95% CI 0.5-2.3) for the QMG score, 1.2 (95% CI 0.5-1.8) for the MG-ADL score, and 2.0 (95% CI 0.03-3.91) for the MG-QoL15r score. The post hoc cost-utility analysis showed lower annual societal costs (€6,565, 95% CI €328-€15,945) and annual improved QALYs (0.106, 95% CI 0.019-0.210) for patients using pyridostigmine. DISCUSSION: This trial showed that, in patients with AChR MG chronically treated with pyridostigmine, pyridostigmine demonstrated benefit over placebo across all efficacy outcome measures and substantially reduced societal costs. TRIAL REGISTRATION INFORMATION: The trial was registered at EudraCT (2021-004110-20, registration date: July 12, 2022) and ClinicalTrials.gov (NCT05919407, registration date: June 16, 2023). First patient enrolled: March 23, 2023. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that, in adults with AChR ab-positive ocular or generalized MG on stable standard-of-care therapy and currently using pyridostigmine, pyridostigmine improves MG symptoms compared with placebo.
9 Apr 2026
Read appraisal →Journal of the American Heart Association
Beyond Composite Indices: Comprehensive Social Determinants Improve Heart Failure Readmission Prediction
BACKGROUND: Heart failure (HF) hospitalization readmissions are associated with a high mortality rate and strain the health care system. Both clinical factors and social determinants of health (SDOH) predict HF readmissions, but the optimal approach to incorporating area-level SDOH data remains unclear. METHODS: We merged census tract- and county-level SDOH measures with electronic health record data in a retrospective cohort of 33 579 Black and White patients with HF (Emory Healthcare, 2010-2018). Six combinations of electronic health record data with 752 area-level SDOH were evaluated using multiple machine learning models (logistic regression, random forest, XGBoost) to predict 30-day HF readmission. Models were assessed for predictive performance using area under the receiver operating characteristic curve and algorithmic fairness across race using the equalized odds ratio. RESULTS: Expanded SDOH predictor sets improved predictive performance and algorithmic fairness compared with traditional SDOH indices. The XGBoost model using expanded SDOH alongside clinical predictors provided better predictive performance (area under the receiver operating characteristic curve, 0.671) and improved algorithmic fairness across patient race (equalized odds ratio, 0.437) than models with traditional indices (area under the receiver operating characteristic curve, 0.632; equalized odds ratio, 0.329). Feature-importance analysis revealed that specific environmental predictors (housing cost burden, air quality) ranked among top predictors alongside clinical biomarkers. County-level SDOH outperformed census tract-level SDOH and matched prediction performance of clinical predictors alone. CONCLUSIONS: Including hundreds of individual SDOH indicators rather than traditional composite indices improves machine learning models' ability to predict 30-day HF readmissions. While performance gains are modest, inclusion of specific environmental factors may provide greater clinical utility and improved equity across racial groups than composite SDOH measures for guiding further research and preventive interventions.
8 Apr 2026
Read appraisal →BMJ open
Synthetic data-augmented machine learning for 30-day readmission prediction in patients with chronic conditions: a retrospective real-world study
OBJECTIVES: To develop and evaluate an explainable machine learning framework enhanced with synthetic data generation to predict unplanned 30-day hospital readmissions among patients with chronic obstructive pulmonary disease (COPD), heart failure (HF) and type 2 diabetes mellitus (T2DM), and to identify key clinical and social predictors of readmission. DESIGN: A retrospective cohort study using electronic health record data incorporating both structured variables and information extracted from unstructured clinical notes. Synthetic data were generated using advanced resampling and deep learning-based techniques to address outcome imbalance and improve model training. SETTING: Intensive care unit and general ward admissions at a single tertiary academic medical centre included in the MIMIC-IV (Medical Information Mart for Intensive Care IV) database. PARTICIPANTS: Adult patients (≥18 years) were admitted with a primary diagnosis of COPD (n=14 050), HF (n=7097) or T2DM (n=12 735) between 2008 and 2019, with complete 30-day follow-up and no in-hospital mortality during the index admission. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was unplanned all-cause hospital readmission within 30-days of discharge. Predictors were drawn from six domains, including demographics, comorbidities, clinical acuity, therapies, behavioural factors and care continuity. Predictive performance was evaluated using multiple machine learning methods and fivefold cross-validation, with model interpretability assessed using established goal and local explanation approaches. RESULTS: Ensemble-based machine learning models demonstrated the strongest predictive performance across all three disease cohorts. Key predictors of readmission included higher illness severity, greater comorbidity burden, medication non-adherence, gaps in preventive care and limited social support. Models incorporating synthetic data augmentation showed improved discrimination compared with models trained on original data alone. CONCLUSIONS: An explainable synthetic-data driven framework incorporating clinical, behavioural and social data can support prediction of 30-day readmissions among patients with common chronic conditions using routinely available electronic health record data.
5 Apr 2026
Read appraisal →The New England journal of medicine
Left Atrial Appendage Closure or Medical Therapy in Atrial Fibrillation
BACKGROUND: Catheter-based closure of the left atrial appendage is an alternative to oral anticoagulation for stroke prevention in patients with atrial fibrillation. The effectiveness of this strategy, as compared with physician-directed best medical care, in patients at high risk for stroke and bleeding is unknown. METHODS: In this multicenter randomized trial conducted in Germany, we assigned patients with atrial fibrillation and a high risk of stroke and bleeding to undergo left atrial appendage closure or to receive physician-directed best medical care (including direct oral anticoagulants, if eligible). The primary end point, tested for noninferiority, was a composite of stroke (ischemic or hemorrhagic), systemic embolism, major bleeding, or cardiovascular or unexplained death, assessed in a time-to-event analysis. The noninferiority margin was a hazard ratio of 1.3. RESULTS: A total of 912 adult patients underwent randomization. The primary end-point analysis included 446 patients who were assigned to undergo left atrial appendage closure (device group) and 442 who were assigned to physician-directed best medical care (medical-therapy group). The mean (±SD) age was 77.9±7.1 years; 38.6% of the patients were women, the mean CHA2DS2-VASc score was 5.2±1.5 (range, 0 to 9, with higher scores indicating a greater risk of stroke), and the mean HAS-BLED score was 3.0±0.9 (range, 0 to 9, with higher scores indicating higher risk of bleeding). After a median follow-up of 3 years (interquartile range, 1.7 to 4.7), a first primary end-point event had occurred in 155 patients (incidence per 100 patient-years, 16.8) in the device group and in 127 patients (incidence per 100 patient-years, 13.3) in the medical-therapy group (difference in restricted mean survival time, -0.36 years; 95% confidence interval, -0.70 to -0.01; P = 0.44 for noninferiority). Serious adverse events occurred in 368 patients (82.5%) in the device group and 342 (77.4%) in the medical-therapy group. CONCLUSIONS: Among patients with atrial fibrillation at high risk for stroke and bleeding, left atrial appendage closure was not noninferior to physician-directed best medical care with regard to a composite end point of stroke, systemic embolism, major bleeding, or cardiovascular or unexplained death. (Funded by the German Center for Cardiovascular Research; CLOSURE-AF ClinicalTrials.gov number, NCT03463317.).
4 Apr 2026
Read appraisal →