Severe cholestatic jaundice after a single administration of ajmaline; a case report and review of the literature.

BACKGROUND: Ajmaline is a pharmaceutical agent now administered globally for a variety of indications, particularly investigation of suspected Brugada syndrome. There have been previous reports suggesting that repetitive use of this agent may cause severe liver injury, but little evidence exists demonstrating the same effect after only a single administration. CASE PRESENTATION: A 33-year-old man of Libyan origin with no significant past medical history underwent an ajmaline provocation test for investigation of suspected Brugada syndrome. Three weeks later, he presented with painless cholestatic jaundice which peaked in severity at eleven weeks after the test. Blood tests confirmed no evidence of autoimmune or viral liver disease, whilst imaging confirmed the absence of biliary tract obstruction. A liver biopsy demonstrated centrilobular cholestasis and focal rosetting of hepatocytes, consistent with a cholestatic drug reaction. Over the course of the next few months, he began to improve clinically and biochemically, with complete resolution by one year post-exposure. CONCLUSION: Whilst ajmaline-related hepatotoxicity was well-recognised in the era in which the drug was administered as a regular medication, clinicians should be aware that ajmaline may induce severe cholestatic jaundice even after a single dose administration

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Stratification of inflammatory bowel disease outpatients by disease activity and risk of complications to guide out-of-hospital monitoring: a patient-centred quality improvement project.

Background: Inflammatory bowel disease (IBD) is a chronic relapsing-remitting condition affecting 600 000 people in the UK. Traditionally, patients attend outpatient clinics for monitoring regardless of their symptoms or risk of developing complications. This can lead to a mismatch between need and access: patients in remission given elective appointments displace those in need of urgent specialist attention. Novel initiatives implemented in the UK to improve outpatient monitoring have often required a well-maintained patient registry, empowered patients and significant information technology support. Design and strategy: In this large-scale quality improvement project at St Mark's Hospital, a tertiary centre for IBD, we stratified over 1000 patients attending three non-complex IBD clinics over 12 months according to disease activity and risk profile. The aim was to offer a choice and subsequently transfer 50% of eligible patients to specialist nurse-led telephone clinics and demonstrate non-inferior satisfaction levels to existing outpatient follow-up. We also sought to ensure there was timely access to a newly established rapid access clinic for patients requiring urgent specialist attention.A core project team consisting of healthcare professionals, patients and quality improvement scientists met regularly. The team tested and scaled up interventions using 'Plan-Do-Study-Act' cycles within the 'Model for Improvement' framework and analysed data continuously using statistical process charts. Results: Over 12 months, the average number of eligible patients transferred to telephone clinics rose from 17.6% (42/239) using a questionnaire method to 59.3% (73/123) using active discussion in clinic. Patient satisfaction scores remained high and non-inferior to baseline scores in face-to-face clinics. The median waiting time to be seen in the rapid access clinic was 6.5 days. Conclusion: This is the first published study to report on the successful stratification of patients with IBD based on disease activity and risk of complications to create a more responsive, sustainable and patient-centred model for IBD monitoring

Implementation of an intervention bundle leads to quality improvement in ulcerative colitis endoscopy reporting

BACKGROUND: Accurate and detailed endoscopy reporting in ulcerative colitis (UC) is critical for clinical decision‐making. High‐quality reporting involves inclusion of several criteria, previously identified by an independent group of experts (Building Research in IBD Globally (BRIDGe) group). Few studies have evaluated UC reporting quality. Our aim was to evaluate the impact of an intervention bundle designed to standardise and improve UC endoscopy reporting. METHODS: This intervention bundle included: integration of a template into reporting software; endoscopist training; instructional posters in endoscopy rooms; cohorting patients onto specific lists. Reporting quality was judged against 10 criteria recommended by BRIDGe. In phase one, UC endoscopy reports were retrospectively evaluated at a centre with prior implementation of the intervention bundle and compared to six centres without. In phase two, the intervention bundle was prospectively implemented and evaluated at a single centre. RESULTS: In phase one, the intervention was associated with greater inclusion of BRIDGe reporting criteria from median 5 (IQR 5‐7) to 7 (5‐8), P < 0.0001. This was replicated in phase two, with improved reporting after the intervention from 5 (4‐6) to 6 (5‐8), P < 0.0001. Reporting of endoscopic indices was more frequent in the centre with prior intervention (77.7% (202/260) vs 44.4% (400/900), OR 4.35 95%CI 3.16‐6.00, P < 0.0001). In phase two, implementation of the bundle increased the use of endoscopic indices pre‐intervention vs post‐intervention (57.7% (131/190) vs 69.6% (117/168), OR 1.68 95%CI 1.1‐2.56, P = 0.02). CONCLUSION: This is the first study to demonstrate that an intervention bundle can achieve greater standardisation and improve UC endoscopy reporting