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      Research in the context of coronavirus disease 2019: Considerations for critical care environments

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          Abstract

          Disasters and public health emergencies, such as coronavirus disease 2019 (COVID-19), by their very nature, overwhelm the operational capacity of health services to provide their normal level and array of services. From a health service perspective, this may include any event that results in the need for a health service to adapt their business as usual practices in an attempt to restore and maintain the normal day-to-day health services and standards of care. 1 This is of importance as the inability to provide normal operational capacity results in increased morbidity and mortality for those patients in the health service and for those needing access to the health service. There is a paucity of research regarding the impact of disasters and public health emergencies on intensive care units. This was exemplified in a recent review of the literature published in Australian Critical Care examining the impact of mass casualty incidents, such as pandemics, earthquakes, and deliberate acts of harm. 2 This review identified seven articles which highlighted a number of impacts on intensive care units such as insufficient bed numbers, a lack of resources and supplies, a decline in staffing levels over the duration of the incident, and the need for staff education and training. The authors called for further research regarding mass casualty incidents and the impact on intensive care units due to the lack of research in this area. This editorial echoes the call regarding the need to undertake research in the critical care context of disasters and public health emergencies, such as COVID-19; however, this call is balanced with some key considerations for individual researchers, organisations that facilitate research, and journals that publish research. In particular, these considerations focus on overlapping concepts such as the need to balance opportunity with research purpose and quality. For many researchers, disasters and public health emergencies represent opportunities to better understand from a patient, family, clinicians, or health service perspective our preparedness, response, and recovery to inform future preparedness. However, just because there is an opportunity to do research, this does not mean that the opportunity should be grasped. Broad stroking, nonspecific, and superficial research floods the disaster and public health research landscape. Often this research would be considered a low-hanging fruit, boosting an individual researcher's output; however, the meaning may be insufficient to enhance in-depth understandings. Robust research takes time, and the opportunistic researcher may have a sense of urgency, not wanting to take stock of the purpose and quality of their work. Furthermore, during disasters and public health emergencies, collaboration between researchers could be strengthened. At the time of publishing this editorial, there are at least five national surveys requesting critical care nurses as participants. Many of these surveys are overlapping in terms of aims and questions. On examination, some are superficial, lacking any depth to provide a meaningful contribution. There are a number of governing organisations that facilitate research, including human research ethics committees and membership associations, that allow access to their membership database. Clinicians, patients, and families have a heightened level of vulnerability during disasters and public health emergencies. As such, researchers should not seek exemption from an ethical review, nor should ethics committees offer it. We have seen examples of research during COVID-19 that would normally require full ethical review, instead ‘slipping through’ with an exemption to ethical review. The assumption is that such a strategy is to expedite the research progress and to collect data that is timely. Instead, during disasters and public health emergencies, rigour in research ethics and the protection of research participants should be strengthened. During disasters and public health emergencies, requests to access members of associations may increase. Such an increase places burden on both the association and membership. Associations should place time and value in upcoming research that is of importance to their membership, rather than distributing request for participation on a first-come basis; strategies that prioritise research against an established research agenda should be developed. 3 Additional strategies may include the need for researchers to submit an ‘intention to access the membership’, before the formal request to access membership databases. This may assist in identifying future membership access requests and will help manage overresearching, which has been demonstrated to result in research fatigue, and therefore decreased research quality. 4 The publication of research related to COVID-19 is of importance to disseminate findings of clinical care, understandings of disease trajectory, and health service preparedness and response. However, journals should not feel pressured to publish articles related to emerging topics. Instead, a considered approach should be undertaken that prioritises articles, considers reviewers, and publishes high-quality articles rather than fast-tracking publications where the usual quality checks might be overlooked. The appropriate management, due consideration, and review of articles take time. This process is often undertaken by the good will of volunteering clinicians and academicians with an interest in the journals’ aim and purpose. For example, Australian Critical Care has had a threefold increase in submissions compared with the same time period in 2019 (1 March to 30 June). Of the submissions received in the 2020 time period, one-quarter (n = 32) have been related to COVID-19. Few have progressed through to peer review. Of course, there are many more articles, including research, letters, and opinion papers, published in other critical care, general medical, or infectious diseases journals. An even greater number are published in preprint servers such as MedRχiv where just using the search COVID resulted in 4671 results. 5 The nature of preprint servers means that this work is not published and is widely available but has not undergone a peer-review process. Preprint servers might facilitate the perceived need for urgency to disseminate information; however, maintaining rigour and quality in publication practices is essential. For Australian Critical Care, this has meant that any COVID-19–related submission is immediately prioritised for editorial review and, if the manuscript progresses to peer review, the reviewers are asked to provide comment in 7–10 working days. Accepted manuscripts are fast-tracked by the publisher through the publication process so that the work is made available online as quickly as possible. Sometimes, however, the need to expedite publishing may mean that errors which would have otherwise been identified may go unnoticed. At the time of writing this article, there have been 22 COVID-19–related research publications retracted 6 (https://retractionwatch.com/retracted-coronavirus-covid-19-papers/). Most well-known ones are the recent retractions of COVID-19–related publications in well-respected journals, such as the Lancet 7 and New England Journal of Medicine, 8 primarily owing to the inability of third parties being able to verify the data used for analysis. Such examples reinforce the need for adherence to good publication practice. 9 In summary, research during disasters and public health emergencies, such as COVID-19, should be carefully considered before it is commenced. First, for individual researchers, this means embarking on high-quality, collaborative, and meaningful research, resisting the temptation to quickly grasp low-hanging research, which has the potential to be expedited at the jeopardy of quality. Second, for organisations that facilitate research through funding support or access to potential participants, supporting research with high scientific rigour should be maintained and strategies implemented to facilitate collaborative research particularly when it becomes apparent that duplication of research efforts is imminent. Finally, journals must be agile so that they can quickly respond to the need for rapid dissemination of information while still maintaining established standards of good publishing practice.

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          Most cited references7

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          Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19

          Abstract Background Coronavirus disease 2019 (Covid-19) may disproportionately affect people with cardiovascular disease. Concern has been aroused regarding a potential harmful effect of angiotensin-converting–enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) in this clinical context. Methods Using an observational database from 169 hospitals in Asia, Europe, and North America, we evaluated the relationship of cardiovascular disease and drug therapy with in-hospital death among hospitalized patients with Covid-19 who were admitted between December 20, 2019, and March 15, 2020, and were recorded in the Surgical Outcomes Collaborative registry as having either died in the hospital or survived to discharge as of March 28, 2020. Results Of the 8910 patients with Covid-19 for whom discharge status was available at the time of the analysis, a total of 515 died in the hospital (5.8%) and 8395 survived to discharge. The factors we found to be independently associated with an increased risk of in-hospital death were an age greater than 65 years (mortality of 10.0%, vs. 4.9% among those ≤65 years of age; odds ratio, 1.93; 95% confidence interval [CI], 1.60 to 2.41), coronary artery disease (10.2%, vs. 5.2% among those without disease; odds ratio, 2.70; 95% CI, 2.08 to 3.51), heart failure (15.3%, vs. 5.6% among those without heart failure; odds ratio, 2.48; 95% CI, 1.62 to 3.79), cardiac arrhythmia (11.5%, vs. 5.6% among those without arrhythmia; odds ratio, 1.95; 95% CI, 1.33 to 2.86), chronic obstructive pulmonary disease (14.2%, vs. 5.6% among those without disease; odds ratio, 2.96; 95% CI, 2.00 to 4.40), and current smoking (9.4%, vs. 5.6% among former smokers or nonsmokers; odds ratio, 1.79; 95% CI, 1.29 to 2.47). No increased risk of in-hospital death was found to be associated with the use of ACE inhibitors (2.1% vs. 6.1%; odds ratio, 0.33; 95% CI, 0.20 to 0.54) or the use of ARBs (6.8% vs. 5.7%; odds ratio, 1.23; 95% CI, 0.87 to 1.74). Conclusions Our study confirmed previous observations suggesting that underlying cardiovascular disease is associated with an increased risk of in-hospital death among patients hospitalized with Covid-19. Our results did not confirm previous concerns regarding a potential harmful association of ACE inhibitors or ARBs with in-hospital death in this clinical context. (Funded by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital.)
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            RETRACTED: Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis

            Summary Background Hydroxychloroquine or chloroquine, often in combination with a second-generation macrolide, are being widely used for treatment of COVID-19, despite no conclusive evidence of their benefit. Although generally safe when used for approved indications such as autoimmune disease or malaria, the safety and benefit of these treatment regimens are poorly evaluated in COVID-19. Methods We did a multinational registry analysis of the use of hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19. The registry comprised data from 671 hospitals in six continents. We included patients hospitalised between Dec 20, 2019, and April 14, 2020, with a positive laboratory finding for SARS-CoV-2. Patients who received one of the treatments of interest within 48 h of diagnosis were included in one of four treatment groups (chloroquine alone, chloroquine with a macrolide, hydroxychloroquine alone, or hydroxychloroquine with a macrolide), and patients who received none of these treatments formed the control group. Patients for whom one of the treatments of interest was initiated more than 48 h after diagnosis or while they were on mechanical ventilation, as well as patients who received remdesivir, were excluded. The main outcomes of interest were in-hospital mortality and the occurrence of de-novo ventricular arrhythmias (non-sustained or sustained ventricular tachycardia or ventricular fibrillation). Findings 96 032 patients (mean age 53·8 years, 46·3% women) with COVID-19 were hospitalised during the study period and met the inclusion criteria. Of these, 14 888 patients were in the treatment groups (1868 received chloroquine, 3783 received chloroquine with a macrolide, 3016 received hydroxychloroquine, and 6221 received hydroxychloroquine with a macrolide) and 81 144 patients were in the control group. 10 698 (11·1%) patients died in hospital. After controlling for multiple confounding factors (age, sex, race or ethnicity, body-mass index, underlying cardiovascular disease and its risk factors, diabetes, underlying lung disease, smoking, immunosuppressed condition, and baseline disease severity), when compared with mortality in the control group (9·3%), hydroxychloroquine (18·0%; hazard ratio 1·335, 95% CI 1·223–1·457), hydroxychloroquine with a macrolide (23·8%; 1·447, 1·368–1·531), chloroquine (16·4%; 1·365, 1·218–1·531), and chloroquine with a macrolide (22·2%; 1·368, 1·273–1·469) were each independently associated with an increased risk of in-hospital mortality. Compared with the control group (0·3%), hydroxychloroquine (6·1%; 2·369, 1·935–2·900), hydroxychloroquine with a macrolide (8·1%; 5·106, 4·106–5·983), chloroquine (4·3%; 3·561, 2·760–4·596), and chloroquine with a macrolide (6·5%; 4·011, 3·344–4·812) were independently associated with an increased risk of de-novo ventricular arrhythmia during hospitalisation. Interpretation We were unable to confirm a benefit of hydroxychloroquine or chloroquine, when used alone or with a macrolide, on in-hospital outcomes for COVID-19. Each of these drug regimens was associated with decreased in-hospital survival and an increased frequency of ventricular arrhythmias when used for treatment of COVID-19. Funding William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women's Hospital.
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              Good Publication Practice for Communicating Company-Sponsored Medical Research: GPP3.

              This updated Good Publication Practice (GPP) guideline, known as GPP3, builds on earlier versions and provides recommendations for individuals and organizations that contribute to the publication of research results sponsored or supported by pharmaceutical, medical device, diagnostics, and biotechnology companies. The recommendations are designed to help individuals and organizations maintain ethical and transparent publication practices and comply with legal and regulatory requirements. These recommendations cover publications in peer-reviewed journals and presentations (oral or poster) at scientific congresses. The International Society for Medical Publication Professionals invited more than 3000 professionals worldwide to apply for a position on the steering committee, or as a reviewer, for this guideline. The GPP2 authors reviewed all applications (n = 241) and assembled an 18-member steering committee that represented 7 countries and a diversity of publication professions and institutions. From the 174 selected reviewers, 94 sent comments on the second draft, which steering committee members incorporated after discussion and consensus. The resulting guideline includes new sections (Principles of Good Publication Practice for Company-Sponsored Medical Research, Data Sharing, Studies That Should Be Published, and Plagiarism), expands guidance on the International Committee of Medical Journal Editors' authorship criteria and common authorship issues, improves clarity on appropriate author payment and reimbursement, and expands information on the role of medical writers. By following good publication practices (including GPP3), individuals and organizations will show integrity; accountability; and responsibility for accurate, complete, and transparent reporting in their publications and presentations.
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                Author and article information

                Contributors
                Journal
                Aust Crit Care
                Aust Crit Care
                Australian Critical Care
                Published by Elsevier Ltd on behalf of Australian College of Critical Care Nurses Ltd.
                1036-7314
                1036-7314
                16 July 2020
                July 2020
                16 July 2020
                : 33
                : 4
                : 309-310
                Affiliations
                [a ]Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia
                [b ]Department of Emergency Medicine, Gold Coast Health, Gold Coast, Queensland, Australia
                Author notes
                []Corresponding author at: Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia. jamie@ 123456jamieranse.com
                Article
                S1036-7314(20)30246-0
                10.1016/j.aucc.2020.06.004
                7365645
                fb116f90-6d6b-426e-813d-0e6d33a91255
                © 2020 Published by Elsevier Ltd on behalf of Australian College of Critical Care Nurses Ltd.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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