Limit of detection of troponin discharge strategy versus usual care: randomised controlled trial

Introduction: The clinical effectiveness of a 'rule-out' acute coronary syndrome (ACS) strategy for emergency department patients with chest pain, incorporating a single undetectable high-sensitivity cardiac troponin (hs-cTn) taken at presentation, together with a non-ischaemic ECG, remains unknown. Methods: A randomised controlled trial, across eight hospitals in the UK, aimed to establish the clinical effectiveness of an undetectable hs-cTn and ECG (limit of detection and ECG discharge (LoDED)) discharge strategy. Eligible adult patients presented with chest pain; the treating clinician intended to perform investigations to rule out an ACS; the initial ECG was non-ischaemic; and peak symptoms occurred <6 hours previously. Participants were randomised 1:1 to either the LoDED strategy or the usual rule-out strategy. The primary outcome was discharge from the hospital within 4 hours of arrival, without a major adverse cardiac event (MACE) within 30 days. Results: Between June 2018 and March 2019, 632 patients were randomised; 3 were later withdrawn. Of 629 patients (age 53.8 (SD 16.1) years, 41% women), 7% had a MACE within 30 days. For the LoDED strategy, 141 of 309 (46%) patients were discharged within 4 hours, without MACE within 30 days, and for usual care, 114 of 311 (37%); pooled adjusted OR 1.58 (95% CI 0.84 to 2.98). No patient with an initial undetectable hs-cTn had a MACE within 30 days. Conclusion: The LoDED strategy facilitates safe early discharge in >40% of patients with chest pain. Clinical effectiveness is variable when compared with existing rule-out strategies and influenced by wider system factors.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.g This trial was funded by the National Institute for Health Research (NIHR) through its Research for Patient Benefit programme (grant reference number PBPG-0416-20012). JRB is an NIHR senior investigator.published version, accepted version, submitted versio

Modified Valsalva manoeuvre to treat recurrent supraventricular tachycardia: description of the technique and its successful use in a patient with a previous near fatal complication of DC cardioversion

Patients with attacks of re-entrant supraventricular tachycardia (SVT) frequently present to the emergency department (ED). The Valsalva manoeuvre (VM) is the most effective and safe vagal manoeuvre and advocated as the first-line treatment in stable patients but has a relatively low cardioversion success rate. Improving its efficacy would reduce patients' exposure to the side effects and complications of second-line treatments and has other potential benefits. We describe a modification to the VM, which is currently being studied, and present the case of a 23-year-old patient who was successfully treated with this modified VM after a previous near-fatal complication of direct current (DC) cardioversion.RD&E staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted

Behavior of Coupled Automata

We study the nature of statistical correlations that develop between systems of interacting self-organized critical automata (sandpiles). Numerical and analytical findings are presented describing the emergence of synchronization between sandpiles and the dependency of this synchronization on factors such as variations in coupling strength, toppling rule probabilities, symmetric versus asymmetric coupling rules, and numbers of sandpiles

Factors related to medical students’ and doctors’ attitudes towards older patients: A systematic review

Background:Studies have sought to identify the possible determinants of medical students’ and doctors’ attitudes towards older patients by examining relationships with a variety of factors: demographic; educational/training; exposure to older people; personality/cognitive; and job/career factors. This review collates and synthesises these findings. Methods: An electronic search of ten databases was performed (ABI/Inform, ASSIA, British Nursing Index, CINAHL, Informa Health, Medline, PsycINFO, Science Direct, Scopus, and Web of Science) through to 7 February 2017. Results: The main search identified 2332 articles; 37 studies met the eligibility criteria set. All included studies analysed self-reported attitudes based on correlational analyses or difference testing, therefore causation could not be determined. However, self-reported positive attitudes towards older patients were related to: (i) intrinsic motivation for studying medicine; (ii) increased preference for working with older patients; and (iii) good previous relationships with older people. Additionally, more positive attitudes were also reported in those with higher knowledge scores but these may relate to the use of a knowledge assessment which is an indirect measure of attitudes (i.e. Palmore’s Facts on Aging Quizzes). Four out of the five high quality studies included in this review reported more positive attitudes in females compared to males. Conclusion:This paper identifies factors associated with medical students’ and doctors’ positive attitudes towards older patients. Future research could bring greater clarity to the relationship between knowledge and attitudes by using a knowledge measure which is distinct from attitudes and also measures knowledge that is relevant to clinical care

Randomised evaluation of modified valsalva effectiveness in re-entrant tachycardias (REVERT) study

Introduction: The Valsalva manoeuvre (VM) is a recommended first-line physical treatment for patients with re-entrant supraventricular tachycardia (SVT), but is often ineffective in standard practice. A failed VM is typically followed by treatment with intravenous adenosine, which patients often find unpleasant. VM effectiveness might be improved by a modification to posture which exaggerates the manoeuvre's vagal response and reduces the need for further emergency treatment. Methods and analysis: This is a multicentre randomised controlled clinical trial in 10 UK emergency departments (EDs). It compares a standard VM with a modified VM incorporating leg elevation and a supine posture after a standardised strain in stable adult patients presenting to the ED with SVT. The primary outcome measure is return to sinus rhythm on a 12-lead ECG. Secondary outcome measures include the need for treatment with adenosine or other antiarrhythmic treatments and the time patients spend in the ED. We plan to recruit approximately 372 patients, with 80% power to demonstrate an absolute improvement in cardioversion rate of 12%. An improvement of this magnitude through the use of a modified VM would be of significant benefit to patients and healthcare providers, and justify a change to standard practice. Ethics and dissemination: The study has been approved by the South West - Exeter Research Ethics Committee (REC reference 12/SW/0281). The trial will be published in an international peer reviewed journal. Study findings will be sent to the European and International resuscitation councils to inform future revisions of arrhythmia management guidelines. Results: The trial will also be disseminated at international conferences and to patients through the Arrhythmia Alliance, a patient support charity. Registration: The study is registered with Current Controlled Trials (ISRCTN67937027) and has been adopted by the National Institute for Health Research (NIHR) Clinical Research Network

Postural modification to the standard Valsalva manoeuvre for emergency treatment of supraventricular tachycardias (REVERT): A randomised controlled trial

© 2015 Appelboam et al. Open Access article distributed under the terms of CC BY-ND-NC. Background The Valsalva manoeuvre is an internationally recommended treatment for supraventricular tachycardia, but cardioversion is rare in practice (5-20%), necessitating the use of other treatments including adenosine, which patients often find unpleasant. We assessed whether a postural modification to the Valsalva manoeuvre could improve its effectiveness. Methods We did a randomised controlled, parallel-group trial at emergency departments in England. We randomly allocated adults presenting with supraventricular tachycardia (excluding atrial fibrillation and flutter) in a 1:1 ratio to undergo a modified Valsalva manoeuvre (done semi-recumbent with supine repositioning and passive leg raise immediately after the Valsalva strain), or a standard semi-recumbent Valsalva manoeuvre. A 40 mm Hg pressure, 15 s standardised strain was used in both groups. Randomisation, stratified by centre, was done centrally and independently, with allocation with serially numbered, opaque, sealed, tamper-evident envelopes. Patients and treating clinicians were not masked to allocation. The primary outcome was return to sinus rhythm at 1 min after intervention, determined by the treating clinician and electrocardiogram and confirmed by an investigator masked to treatment allocation. This study is registered with Current Controlled Trials (ISRCTN67937027). Findings We enrolled 433 participants between Jan 11, 2013, and Dec 29, 2014. Excluding second attendance by five participants, 214 participants in each group were included in the intention-to-treat analysis. 37 (17%) of 214 participants assigned to standard Valsalva manoeuvre achieved sinus rhythm compared with 93 (43%) of 214 in the modified Valsalva manoeuvre group (adjusted odds ratio 3·7 (95% CI 2·3-5·8;

The Building Blocks of Interoperability. A Multisite Analysis of Patient Demographic Attributes Available for Matching.

BackgroundPatient matching is a key barrier to achieving interoperability. Patient demographic elements must be consistently collected over time and region to be valuable elements for patient matching.ObjectivesWe sought to determine what patient demographic attributes are collected at multiple institutions in the United States and see how their availability changes over time and across clinical sites.MethodsWe compiled a list of 36 demographic elements that stakeholders previously identified as essential patient demographic attributes that should be collected for the purpose of linking patient records. We studied a convenience sample of 9 health care systems from geographically distinct sites around the country. We identified changes in the availability of individual patient demographic attributes over time and across clinical sites.ResultsSeveral attributes were consistently available over the study period (2005-2014) including last name (99.96%), first name (99.95%), date of birth (98.82%), gender/sex (99.73%), postal code (94.71%), and full street address (94.65%). Other attributes changed significantly from 2005-2014: Social security number (SSN) availability declined from 83.3% to 50.44% (p&lt;0.0001). Email address availability increased from 8.94% up to 54% availability (p&lt;0.0001). Work phone number increased from 20.61% to 52.33% (p&lt;0.0001).ConclusionsOverall, first name, last name, date of birth, gender/sex and address were widely collected across institutional sites and over time. Availability of emerging attributes such as email and phone numbers are increasing while SSN use is declining. Understanding the relative availability of patient attributes can inform strategies for optimal matching in healthcare

APOBECs and Herpesviruses

The apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) family of DNA cytosine deaminases provides a broad and overlapping defense against viral infections. Successful viral pathogens, by definition, have evolved strategies to escape restriction by the APOBEC enzymes of their hosts. HIV-1 and related retroviruses are thought to be the predominant natural substrates of APOBEC enzymes due to obligate single-stranded (ss)DNA replication intermediates, abundant evidence for cDNA strand C-to-U editing (genomic strand G-to-A hypermutation), and a potent APOBEC degradation mechanism. In contrast, much lower mutation rates are observed in double-stranded DNA herpesviruses and the evidence for APOBEC mutation has been less compelling. However, recent work has revealed that Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV), and herpes simplex virus-1 (HSV-1) are potential substrates for cellular APOBEC enzymes. To prevent APOBEC-mediated restriction these viruses have repurposed their ribonucleotide reductase (RNR) large subunits to directly bind, inhibit, and relocalize at least two distinct APOBEC enzymes-APOBEC3B and APOBEC3A. The importance of this interaction is evidenced by genetic inactivation of the EBV RNR (BORF2), which results in lower viral infectivity and higher levels of C/G-to-T/A hypermutation. This RNR-mediated mechanism therefore likely functions to protect lytic phase viral DNA replication intermediates from APOBEC-catalyzed DNA C-to-U deamination. The RNR-APOBEC interaction defines a new pathogen-host conflict that the virus must win in real-time for transmission and pathogenesis. However, partial losses over evolutionary time may also benefit the virus by providing mutational fuel for adaptation

Randomised controlled trial of the Limit of Detection of Troponin and ECG Discharge (LoDED) strategy versus usual care in adult patients with chest pain attending the emergency department: Study protocol

© 2018 Author(s). Published by BMJ. Introduction Observational data suggest a single high-sensitivity troponin blood test taken at emergency department (ED) presentation could be used to rule out major adverse cardiac events (MACE) in 10%-60% of ED patients with chest pain. This is done using an 'undetectable' cut-off (the Limit of Detection: LoD). We combined the LoD cut-off with ECG findings to create the LoDED strategy. We aim to establish whether the LoDED strategy works under real-life conditions, when compared with existing strategies, in a way that is cost-effective and acceptable to patients. Methods and analysis This is a parallel-group pragmatic randomised controlled trial across UK EDs. Adults presenting to ED with suspected cardiac chest pain will be randomised 1:1. Existing rule-out strategies in current use across study centres, using serial high-sensitivity troponin testing, will be compared with the LoDED strategy. The primary outcome is successful early discharge (discharge from hospital within 4 hours of arrival) without MACE occurring within 30 days. Secondary outcomes include initial length of hospital stay; comparative costs; patient satisfaction and acceptability to patients. To detect a 9% difference between the early discharge rates (assuming an 8% rate in the standard care group) with 90% power, 594 patients need to be recruited, assuming a 95% follow-up rate. Ethics and dissemination The study has been approved by the Frenchay Research Ethics Committee (reference 18/SW/0038). Results will be published in an international peer-reviewed journal. Lay summaries will be made available to patients