Protocol: does sodium nitrite administration reduce ischaemia-reperfusion injury in patients presenting with acute ST segment elevation myocardial infarction? Nitrites in acute myocardial infarction (NIAMI)

BACKGROUND: Whilst advances in reperfusion therapies have reduced early mortality from acute myocardial infarction, heart failure remains a common complication, and may develop very early or long after the acute event. Reperfusion itself leads to further tissue damage, a process described as ischaemia-reperfusion-injury (IRI), which contributes up to 50% of the final infarct size. In experimental models nitrite administration potently protects against IRI in several organs, including the heart. In the current study we investigate whether intravenous sodium nitrite administration immediately prior to percutaneous coronary intervention (PCI) in patients with acute ST segment elevation myocardial infarction will reduce myocardial infarct size. This is a phase II, randomised, placebo-controlled, double-blinded and multicentre trial. METHODS AND OUTCOMES: The aim of this trial is to determine whether a 5 minute systemic injection of sodium nitrite, administered immediately before opening of the infarct related artery, results in significant reduction of IRI in patients with first acute ST elevation myocardial infarction (MI). The primary clinical end point is the difference in infarct size between sodium nitrite and placebo groups measured using cardiovascular magnetic resonance imaging (CMR) performed at 6-8 days following the AMI and corrected for area at risk (AAR) using the endocardial surface area technique. Secondary end points include (i) plasma creatine kinase and Troponin I measured in blood samples taken pre-injection of the study medication and over the following 72 hours; (ii) infarct size at six months; (iii) Infarct size corrected for AAR measured at 6-8 days using T2 weighted triple inversion recovery (T2-W SPAIR or STIR) CMR imaging; (iv) Left ventricular (LV) ejection fraction measured by CMR at 6-8 days and six months following injection of the study medication; and (v) LV end systolic volume index at 6-8 days and six months. FUNDING,ETHICS AND REGULATORY APPROVALS: This study is funded by a grant from the UK Medical Research Council. This protocol is approved by the Scotland A Research Ethics Committee and has also received clinical trial authorisation from the Medicines and Healthcare products Regulatory Agency (MHRA) (EudraCT number: 2010-023571-26)

Intravenous sodium nitrite in acute ST-elevation myocardial infarction: a randomized controlled trial (NIAMI).

AIM: Despite prompt revascularization of acute myocardial infarction (AMI), substantial myocardial injury may occur, in part a consequence of ischaemia reperfusion injury (IRI). There has been considerable interest in therapies that may reduce IRI. In experimental models of AMI, sodium nitrite substantially reduces IRI. In this double-blind randomized placebo controlled parallel-group trial, we investigated the effects of sodium nitrite administered immediately prior to reperfusion in patients with acute ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: A total of 229 patients presenting with acute STEMI were randomized to receive either an i.v. infusion of 70 μmol sodium nitrite (n = 118) or matching placebo (n = 111) over 5 min immediately before primary percutaneous intervention (PPCI). Patients underwent cardiac magnetic resonance imaging (CMR) at 6-8 days and at 6 months and serial blood sampling was performed over 72 h for the measurement of plasma creatine kinase (CK) and Troponin I. Myocardial infarct size (extent of late gadolinium enhancement at 6-8 days by CMR-the primary endpoint) did not differ between nitrite and placebo groups after adjustment for area at risk, diabetes status, and centre (effect size -0.7% 95% CI: -2.2%, +0.7%; P = 0.34). There were no significant differences in any of the secondary endpoints, including plasma troponin I and CK area under the curve, left ventricular volumes (LV), and ejection fraction (EF) measured at 6-8 days and at 6 months and final infarct size (FIS) measured at 6 months. CONCLUSIONS: Sodium nitrite administered intravenously immediately prior to reperfusion in patients with acute STEMI does not reduce infarct size

Advanced demand and a critical analysis of revenue management

Pre-print; author's draftThis paper presents a theoretical framework of advanced demand through six propositions. The framework introduces the concept of acquisition and valuation risks and suggests that advanced demand distribution is rooted in the trade off between them. Furthermore, since advanced buyers may not consume, firms may be able to re-sell capacity relinquished. The study then proposes how refunds could provide additional revenue to firms. The study further suggests theoretical reasons why and when service firms are able to practice revenue management, suggesting that RM tools such as overbooking and demand forecasting may not be the only tools for higher revenue

Frameworks for implementation, uptake and use of digital health interventions in ethnic minority populations: a scoping review using cardiometabolic disease as a case study

Background: Digital health interventions have become increasingly common across health care, both before and during the COVID-19 pandemic. Health inequalities, particularly with respect to ethnicity, may not be considered in frameworks that address the implementation of digital health interventions. We considered frameworks to include any models, theories, or taxonomies that describe or predict implementation, uptake, and use of digital health interventions. Objective: We aimed to assess how health inequalities are addressed in frameworks relevant to the implementation, uptake, and use of digital health interventions; health and ethnic inequalities; and interventions for cardiometabolic disease. Methods: SCOPUS, PubMed, EMBASE, Google Scholar, and gray literature were searched to identify papers on frameworks relevant to the implementation, uptake, and use of digital health interventions; ethnically or culturally diverse populations and health inequalities; and interventions for cardiometabolic disease. We assessed the extent to which frameworks address health inequalities, specifically ethnic inequalities; explored how they were addressed; and developed recommendations for good practice. Results: Of 58 relevant papers, 22 (38%) included frameworks that referred to health inequalities. Inequalities were conceptualized as society-level, system-level, intervention-level, and individual. Only 5 frameworks considered all levels. Three frameworks considered how digital health interventions might interact with or exacerbate existing health inequalities, and 3 considered the process of health technology implementation, uptake, and use and suggested opportunities to improve equity in digital health. When ethnicity was considered, it was often within the broader concepts of social determinants of health. Only 3 frameworks explicitly addressed ethnicity: one focused on culturally tailoring digital health interventions, and 2 were applied to management of cardiometabolic disease. Conclusions: Existing frameworks evaluate implementation, uptake, and use of digital health interventions, but to consider factors related to ethnicity, it is necessary to look across frameworks. We have developed a visual guide of the key constructs across the 4 potential levels of action for digital health inequalities, which can be used to support future research and inform digital health policies

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Updated guidance on the management of COVID-19:from an American Thoracic Society/European Respiratory Society coordinated International Task Force (29 July 2020)

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome-coronavirus-2. Consensus suggestions can standardise care, thereby improving outcomes and facilitating future research. METHODS: An International Task Force was composed and agreement regarding courses of action was measured using the Convergence of Opinion on Recommendations and Evidence (CORE) process. 70% agreement was necessary to make a consensus suggestion. RESULTS: The Task Force made consensus suggestions to treat patients with acute COVID-19 pneumonia with remdesivir and dexamethasone but suggested against hydroxychloroquine except in the context of a clinical trial; these are revisions of prior suggestions resulting from the interim publication of several randomised trials. It also suggested that COVID-19 patients with a venous thromboembolic event be treated with therapeutic anticoagulant therapy for 3 months. The Task Force was unable to reach sufficient agreement to yield consensus suggestions for the post-hospital care of COVID-19 survivors. The Task Force fell one vote shy of suggesting routine screening for depression, anxiety and post-traumatic stress disorder. CONCLUSIONS: The Task Force addressed questions related to pharmacotherapy in patients with COVID-19 and the post-hospital care of survivors, yielding several consensus suggestions. Management options for which there is insufficient agreement to formulate a suggestion represent research priorities.status: Published onlin

Frameworks for implementation, uptake, and use of cardiometabolic disease–related digital health interventions in ethnic minority populations : scoping review

Background: Digital health interventions have become increasingly common across health care, both before and during the COVID-19 pandemic. Health inequalities, particularly with respect to ethnicity, may not be considered in frameworks that address the implementation of digital health interventions. We considered frameworks to include any models, theories, or taxonomies that describe or predict implementation, uptake, and use of digital health interventions. Objective: We aimed to assess how health inequalities are addressed in frameworks relevant to the implementation, uptake, and use of digital health interventions; health and ethnic inequalities; and interventions for cardiometabolic disease. Methods: SCOPUS, PubMed, EMBASE, Google Scholar, and gray literature were searched to identify papers on frameworks relevant to the implementation, uptake, and use of digital health interventions; ethnically or culturally diverse populations and health inequalities; and interventions for cardiometabolic disease. We assessed the extent to which frameworks address health inequalities, specifically ethnic inequalities; explored how they were addressed; and developed recommendations for good practice. Results: Of 58 relevant papers, 22 (38%) included frameworks that referred to health inequalities. Inequalities were conceptualized as society-level, system-level, intervention-level, and individual. Only 5 frameworks considered all levels. Three frameworks considered how digital health interventions might interact with or exacerbate existing health inequalities, and 3 considered the process of health technology implementation, uptake, and use and suggested opportunities to improve equity in digital health. When ethnicity was considered, it was often within the broader concepts of social determinants of health. Only 3 frameworks explicitly addressed ethnicity: one focused on culturally tailoring digital health interventions, and 2 were applied to management of cardiometabolic disease. Conclusions: Existing frameworks evaluate implementation, uptake, and use of digital health interventions, but to consider factors related to ethnicity, it is necessary to look across frameworks. We have developed a visual guide of the key constructs across the 4 potential levels of action for digital health inequalities, which can be used to support future research and inform digital health policies

Effect of the first wave of COVID-19 on Poison Control Centre activities in 21 European countries : an EAPCCT initiative

Peer reviewe

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention