Ipswich Hospital is a large district general hospital in Heath Road, Ipswich, Suffolk, England. It is now managed by East Suffolk and North Essex NHS Foundation Trust which was formed on 1 July 2018 by the merging of Ipswich Hospital NHS Trust with Colchester Hospital University NHS Foundation Trust.
Background/Objectives: Janus Kinase inhibitors (JAKi) are an effective treatment option for rheumatoid arthritis (RA); however, emerging concerns regarding cardiovascular and thromboembolic risk have prompted further investigation. We conducted a systematic review and meta-analysis to compare the risk of major adverse cardiovascular events (MACE) and venous thromboembolism (VTE) in patients receiving JAKi versus other disease-modifying anti-rheumatic drugs (DMARDs). Methods: Following PRISMA 2020 guidelines and a preregistered protocol, we systematically searched PubMed, Embase, and the Cochrane Library. Observational studies and randomized controlled trials (RCTs) reporting MACE or VTE among adults with RA treated with JAKi or comparator DMARDs were included. Hazard ratios (HRs) from observational studies and odds ratios (ORs) from RCTs were pooled using fixed- or random-effects models depending on heterogeneity. A sensitivity analysis was conducted for participants aged ≥ 65 years. Results: Twenty-five observational studies and eight RCTs were included. Across observational studies, the pooled HRs for MACE showed no significant difference between JAKi and other DMARDs, HR = 0.98, 95% CI = 0.85-1.13. This finding remained consistent in individuals aged ≥ 65 years. No increase in MACE risk was observed across RCTs, OR = 1.27, 95% CI = 0.89-1.81. In contrast, JAKi use was associated with a significantly higher risk of VTE in the observational studies (HR = 1.32, 95% CI = 1.08-1.61) but not in the RCTs (OR = 1.69, 95% CI = 0.94-3.02). Conclusions: JAKi use does not appear to increase the risk of MACE compared to DMARDs, including in older adults, but may be associated with a higher risk of VTE. These findings highlight the importance of a personalized approach when considering JAKi therapy, incorporating structured cardiovascular and thrombotic risk assessment, patient preferences, and mitigation of modifiable risk factors.
BACKGROUND:Approximately 10% of hospitalized patients globally report a penicillin allergy, leading to inappropriate antibiotic prescribing and inferior healthcare outcomes. Evidence supporting the effectiveness and widespread implementation of inpatient penicillin direct oral challenge (DOC) is limited. METHODS:A prospective, multicenter, international type 2 hybrid effectiveness-implementation study was conducted in 40 hospitals across 8 countries between November 2022 and May 2025. Adult inpatients with a penicillin allergy underwent assessment using a digital penicillin allergy toolkit (National Antibiotic Allergy Network [NAAN] App). According to site clinical practice, participants received penicillin DOC (effectiveness intervention) or assessment only. Participating sites received bimonthly audit and feedback at least 3 months after site activation (implementation strategy). Observational data were used to emulate a target trial to examine secondary effectiveness outcomes, including antibiotic prescribing at 90 days in DOC versus non-DOC participants. The primary implementation outcome was adoption of the NAAN App within 6 months of site activation. RESULTS:Among 5121 participants assessed, 1573 (30.7%) underwent DOC, of which 1502 (95.5%) were delabeled. Of 71 (4.5%) participants with a positive DOC, 6 (0.4%) had a serious adverse event. Of 1852 inpatients in the target trial analysis, 892 underwent DOC and 960 underwent assessment only. Participants who underwent DOC were more likely to be prescribed penicillin (risk ratio [RR], 13.25 [95% confidence interval {CI}, 7.82-22.46]), and less likely to be prescribed World Health Organization (WHO) "Watch" or "Reserve" antibiotics (RR, 0.73 [95% CI, .60-.89]) at 90 days post evaluation. Within 6 months of site activation, 77 clinicians adopted the NAAN App. CONCLUSIONS:Multidisciplinary adoption of inpatient penicillin DOC was safe and significantly improved penicillin prescribing and reduced use of WHO restricted antibiotics.
Aims:Early aortic stenosis (AS) detection remains challenging, with many patients presenting late when left ventricular dysfunction may be irreversible. We evaluated whether longitudinal AI-enhanced ECG patterns can predict outcomes years before intervention and assessed the community screening potential of the AK-AVS model. Methods and results:We conducted two complementary analyses: (1) community validation of the AK-AVS model in 3632 cardiovascular disease-free ARIC participants, and (2) longitudinal trajectory analysis of 7860 ECGs from 2040 TAVR recipients collected up to 10 years pre-procedure. Unsupervised clustering identified distinct AK-AVS trajectories, with mortality associations assessed using Cox regression and net reclassification improvement. In community screening (n = 16 moderate/severe AS), AK-AVS achieved an AUROC of 0.79, sensitivity 75%, and specificity 75% for moderate/severe AS. At hypothetical screening prevalences of 1-5%, positive predictive values improved to 3.1-14.3%. False-positive predictions identified individuals at 4-fold increased risk for future AS hospitalisation (HR 4.05, P < 0.001) and 52% increased risk for heart failure (HR 1.52, P = 0.02). In the TAVR cohort, trajectory analysis revealed three distinct patterns: Stable Low (19.3%), Accelerated Progression (23.6%), and Persistently High (57.1%). Elevated trajectory groups were older (78.4 and 77.8 vs. 72.6 years, P < 0.001) with higher pacemaker rates (16.4% and 17.3% vs. 10.7%, P = 0.008), despite similar hemodynamic severity. Both elevated patterns independently predicted mortality (Accelerated: HR 1.40, P = 0.03; Persistently High: HR 1.48, P = 0.005) and significantly improved risk reclassification beyond traditional risk scores (NRI 0.069-0.074). Conclusion:Longitudinal AI-ECG trajectory patterns detect disease progression up to 4.5 years before TAVR and enhance mortality prediction beyond traditional risk scores. Community validation shows potential screening utility with 'false-positives' identifying future risk.
Background Acute coronary syndromes in young patients with minimal risk factors pose diagnostic dilemmas. We report a rare case of myocardial infarction and cardiac arrest caused by Takayasu arteritis. Case Summary A 44-year-old Caucasian woman presented with chest pain, syncope, and ventricular tachycardia. Electrocardiogram showed global ischemia with ST-segment elevation in lead aVR. Coronary angiography revealed severe ostial left main coronary artery stenosis with intravascular ultrasound excluding atherosclerosis or dissection. Computed tomography angiography suggested large vessel vasculitis, and positron emission tomography excluded active inflammation. Through multidisciplinary input, a diagnosis of inactive “burnt-out” Takayasu arteritis was made. The patient underwent percutaneous coronary intervention and was managed without immunosuppression. Discussion Takayasu arteritis is a rare cause of coronary ischemia in adults. Coronary ostial stenoses without atherosclerosis or dissection on intravascular imaging should raise suspicion. A multidisciplinary approach alongside multimodal imaging improves outcomes. Take-Home Message This case highlights a rare cause of acute coronary syndrome in a young patient, the usefulness of coronary intravascular imaging when presented with discordant clinical and coronary angiographic findings, and the value of multimodality imaging and the multidisciplinary team.
