Real-world effects of medications for stroke prevention in atrial fibrillation: protocol for a UK population-based non-interventional cohort study with validation against randomised trial results.

INTRODUCTION: Patients with atrial fibrillation experience an irregular heart rate and have an increased risk of stroke; prophylactic treatment with anticoagulation medication reduces this risk. Direct-acting oral anticoagulants (DOACs) have been approved providing an alternative to vitamin K antagonists such as warfarin. There is interest from regulatory bodies on the effectiveness of medications in routine clinical practice; however, uncertainty remains regarding the suitability of non-interventional data for answering questions on drug effectiveness and on the most suitable methods to be used. In this study, we will use data from Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE)-the pivotal trial for the DOAC apixaban-to validate non-interventional methods for assessing treatment effectiveness of anticoagulants. These methods could then be applied to analyse treatment effectiveness in people excluded from or under-represented in ARISTOTLE. METHODS AND ANALYSIS: Patient characteristics from ARISTOTLE will be used to select a cohort of patients with similar baseline characteristics from two UK electronic health record (EHR) databases, Clinical Practice Research Datalink Gold and Aurum (between 1 January 2013 and 31 July 2019). Methods such as propensity score matching and coarsened exact matching will be explored in matching between EHR treatment groups to determine the optimal method of obtaining a balanced cohort.Absolute and relative risk of outcomes in the EHR trial-analogous cohort will be calculated and compared with the ARISTOTLE results; if results are deemed compatible the methods used for matching EHR treatment groups can then be used to examine drug effectiveness over a longer duration of exposure and in special patient groups of interest not studied in the trial. ETHICS AND DISSEMINATION: The study has been approved by the Independent Scientific Advisory Committee of the UK Medicines and Healthcare Products Regulatory Agency. Results will be disseminated in scientific publications and at relevant conferences

Identifying risk factors for progression to critical care admission and death among individuals with acute pancreatitis : a record linkage analysis of Scottish healthcare databases

This study was commissioned by GSK through the Farr Institute/SHIP/eDRIS single portal. DJM is a Clinician Scientist Fellow funded by the Health Foundation/Academy of Medical Sciences.Objectives: Acute pancreatitis (AP) can initiate systemic complications that require support in critical care (CC). Our objective was to use the unified national health record to define the epidemiology of AP in Scotland, with a specific focus on deterministic and prognostic factors for CC admission in AP. Setting: Health boards in Scotland (n=4). Participants: We included all individuals in a retrospective observational cohort with at least one episode of AP (ICD10 code K85) occurring in Scotland from 1 April 2009 to 31 March 2012. 3340 individuals were coded as AP. Methods: Data from 16 sources, spanning general practice, community prescribing, Accident and Emergency attendances, hospital in-patient, CC and mortality registries, were linked by a unique patient identifier in a national safe haven. Logistic regression and gamma models were used to define independent predictive factors for severe AP (sAP) requiring CC admission or leading to death. Results: 2053 individuals (61.5% (95% CI 59.8% to 63.2%)) met the definition for true AP (tAP). 368 patients (17.9% of tAP (95% CI 16.2% to 19.6%)) were admitted to CC. Predictors of sAP were pre-existing angina or hypertension, hypocalcaemia and age 30-39 years, if type 2 diabetes mellitus was present. The risk of sAP was lower in patients with multiple previous episodes of AP. In-hospital mortality in tAP was 5.0% (95% CI 4.1% to 5.9%) overall and 21.7% (95% CI 19.9% to 23.5%) in those with tAP necessitating CC admission. Conclusions: National record-linkage analysis of routinely collected data constitutes a powerful resource to model CC admission and prognosticate death during AP. Mortality in patients with AP who require CC admission remains high.Publisher PDFPeer reviewe

Prevalence, risk factors, clinical consequences, and treatment of enteral feed intolerance during critical illness

BACKGROUND: We aimed to determine the incidence of enteral feed intolerance and factors associated with intolerance and to assess the influence of intolerance on nutrition and clinical outcomes. METHODS: We conducted a retrospective analysis of data from an international observational cohort study of nutrition practices among 167 intensive care units (ICUs). Data were collected on nutrition adequacy, ventilator-free days (VFDs), ICU stay, and 60-day mortality. Intolerance was defined as interruption of enteral nutrition (EN) due to gastrointestinal (GI) reasons (large gastric residuals, abdominal distension, emesis, diarrhea, or subjective discomfort). Logistic regression was used to determine risk factors for intolerance and their clinical significance. A sensitivity analysis restricted to sites specifying a gastric residual volume ≥200 mL to identify intolerance was also conducted. RESULTS: Data from 1,888 ICU patients were included. The incidence of intolerance was 30.5% and occurred after a median 3 days from EN initiation. Patients remained intolerant for a mean (±SD) duration of 1.9 ± 1.3 days . Intolerance was associated with worse nutrition adequacy vs the tolerant (56% vs 64%, P < .0001), fewer VFDs (2.5 vs 11.2, P < .0001), increased ICU stay (14.4 vs 11.3 days, P < .0001), and increased mortality (30.8% vs 26.2, P = .04). The sensitivity analysis demonstrated that intolerance remained associated with negative outcomes. Although mortality was greater among the intolerant patients, this was not statistically significant. CONCLUSIONS: Intolerance occurs frequently during EN in critically ill patients and is associated with poorer nutrition and clinical outcomes.Usha Gungabissoon, Kimberley Hacquoil, Chanchal Bains, Michael Irizarry, George Dukes, Russell Williamson, Adam M. Deane, and Daren K. Heylan