Modernising epidemic science: enabling patient-centred research during epidemics

Background: Emerging and epidemic infectious disease outbreaks are a significant public health problem and global health security threat. As an outbreak begins, epidemiological investigations and traditional public health responses are generally mounted very quickly. However, patient-centred research is usually not prioritised when planning and enacting the response. Instead, the clinical research response occurs subsequent to and separate from the public health response, and is inadequate for evidence-based decision-making at the bedside or in the offices of public health policymakers.Discussion: The deficiencies of the clinical research response to severe acute respiratory syndrome, pandemic influenza, Middle East respiratory syndrome coronavirus and Ebola virus demonstrate that current research models do not adequately inform and improve the quality of clinical care or public health response. Three suggestions for improvements are made. First, integrate the data and sample collection needs for clinical and public health decision-making within a unified framework, combined with a risk-based, rather than a discipline-based, approach to ethical review and consent. Second, develop clinical study methods and tools that are specifically designed to meet the epidemiological and contextual challenges of emerging and epidemic infectious diseases. Third, invest in investigator-led clinical research networks that are primed and incentivised to respond to outbreak infections, and which can call on the support and resources of a central centre of excellence.Conclusions: It is crucial that the field of epidemic science matures to place patients at the heart of the response. This can only be achieved when patient-centred research is integrated in the outbreak response from day one and practical steps are taken to reduce the barriers to the generation of reliable and useful evidence

Whose Lives Do We Flatten Along With “The Curve?”

Ganesh, A., Rato, J. M., Chennupati, V. M., Rojek, A., & Viswanathan, A. (2020). Public Health Responses to COVID-19: Whose Lives Do We Flatten Along With “The Curve?”. Frontiers in public health, 8, [564111]. https://doi.org/10.3389/fpubh.2020.564111The Coronavirus 2019 (COVID-19) pandemic has received varying and evolving public health responses worldwide (1). Sweden remained largely open with health measures aimed most substantively at vulnerable groups, while South Korea implemented a large testing program, combined with extensive efforts to isolate infected people and trace/quarantine contacts. The United Kingdom (UK) considered various approaches before deciding on measures to isolate, quarantine, and promote social-distancing that were eased in mid-July (1); lockdown is now being re-implemented with a surging second wave (2). In contrast to early social-distancing measures in Canada to “flatten the curve,” American states adopted varying approaches, with many states having now relaxed their measures to differing extents (3). China adopted an aggressive approach of quarantining the affected Hubei province and isolating infected populations (4). India was under an ambitious 40-day lockdown, which was then extended until May-31 with districts designated as red/orange/green based on cumulative cases and doubling rate; red zones continued under full lockdown whereas orange/green zones had more relaxed measures (5). Gradual easing of restrictions (“unlock” 1.0 through 5.0) ensued, with lockdown measures nevertheless continuing in designated containment zones (6). Millions of people around the world still face public health measures of one form or another, raising the question: how stringent should government responses be in such pandemics (7), and how long can (or should) such measures continue?publishersversionpublishe

Availability, scope and quality of monkeypox clinical management guidelines globally : a systematic review

This work was supported by the UK Foreign, Commonwealth and Development Office and Wellcome (215091/Z/18/Z) and the Bill & Melinda Gates Foundation (OPP1209135). The GloPID-R Secretariat is a project that receives funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 874667. SL is an MRC Clinical Research Training fellow (MR/T001151/1).Background Monkeypox (MPX) is an important human Orthopoxvirus infection. There has been an increase in MPX cases and outbreaks in endemic and non-endemic regions in recent decades. We appraised the availability, scope, quality and inclusivity of clinical management guidelines for MPX globally. Methods For this systematic review, we searched six databases from inception until 14 October 2021, augmented by a grey literature search until 17 May 2022. MPX guidelines providing treatment and supportive care recommendations were included, with no exclusions for language. Two reviewers assessed the guidelines. Quality was assessed using the Appraisal of Guidelines for Research and Evaluation II tool. Results Of 2026 records screened, 14 guidelines were included. Overall, most guidelines were of low-quality with a median score of 2 out of 7 (range: 1–7), lacked detail and covered a narrow range of topics. Most guidelines focused on adults, five (36%) provided some advice for children, three (21%) for pregnant women and three (21%) for people living with HIV. Treatment guidance was mostly limited to advice on antivirals; seven guidelines advised cidofovir (four specified for severe MPX only); 29% (4/14) tecovirimat, and 7% (1/14) brincidofovir. Only one guideline provided recommendations on supportive care and treatment of complications. All guidelines recommended vaccination as post-exposure prophylaxis (PEP). Three guidelines advised on vaccinia immune globulin as PEP for severe cases in people with immunosuppression. Conclusion Our results highlight a lack of evidence-based clinical management guidelines for MPX globally. There is a clear and urgent need for research into treatment and prophylaxis including for different risk populations. The current outbreak provides an opportunity to accelerate this research through coordinated high-quality studies. New evidence should be incorporated into globally accessible guidelines, to benefit patient and epidemic outcomes. A ‘living guideline’ framework is recommended. PROSPERO registration number CRD42020167361.Publisher PDFPeer reviewe

Clinical characteristics, risk factors and outcomes in patients with severe COVID-19 registered in the International Severe Acute Respiratory and Emerging Infection Consortium WHO clinical characterisation protocol: a prospective, multinational, multicentre, observational study

Due to the large number of patients with severe coronavirus disease 2019 (COVID-19), many were treated outside the traditional walls of the intensive care unit (ICU), and in many cases, by personnel who were not trained in critical care. The clinical characteristics and the relative impact of caring for severe COVID-19 patients outside the ICU is unknown. This was a multinational, multicentre, prospective cohort study embedded in the International Severe Acute Respiratory and Emerging Infection Consortium World Health Organization COVID-19 platform. Severe COVID-19 patients were identified as those admitted to an ICU and/or those treated with one of the following treatments: invasive or noninvasive mechanical ventilation, high-flow nasal cannula, inotropes or vasopressors. A logistic generalised additive model was used to compare clinical outcomes among patients admitted or not to the ICU. A total of 40 440 patients from 43 countries and six continents were included in this analysis. Severe COVID-19 patients were frequently male (62.9%), older adults (median (interquartile range (IQR), 67 (55-78) years), and with at least one comorbidity (63.2%). The overall median (IQR) length of hospital stay was 10 (5-19) days and was longer in patients admitted to an ICU than in those who were cared for outside the ICU (12 (6-23) days versus 8 (4-15) days, p<0.0001). The 28-day fatality ratio was lower in ICU-admitted patients (30.7% (5797 out of 18 831) versus 39.0% (7532 out of 19 295), p<0.0001). Patients admitted to an ICU had a significantly lower probability of death than those who were not (adjusted OR 0.70, 95% CI 0.65-0.75; p<0.0001). Patients with severe COVID-19 admitted to an ICU had significantly lower 28-day fatality ratio than those cared for outside an ICU

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Treating Ebola in eastern DRC

Since the onset of the west Africa Ebola Virus Disease (EVD) outbreak, there has been remarkable progress in efforts to provide patients with improved supportive care and access to experimental treatments. It is reasonable to explore the potential therapeutic value of both pathogen-directed antiviral therapies and host-directed therapies (e.g., monoclonal antibody cocktails). Given unacceptably high mortality rates among EVD patients, treatments demonstrated to be safe and efficacious in clinical trials would likely be welcomed by clinicians and affected communities

Exercise-associated hyponatraemia on the Kokoda Trail

Objective: The objective of the present study was to determine the prevalence of exercise-associated hyponatraemia in hikers/trekkers along the Kokoda Trail. Methods: This was a cross-sectional study of 191 trekkers on the Kokoda Trail, Papua New Guinea. Blood was taken and analysed immediately using point-of-care technology 2days walk from each end of the Trail. Results: The main outcome measure was hyponatraemia defined as serum sodium level less than 135mmol/L. Three participants (1.6%, 95% CI 0.5-4.5%) were found to have mild hyponatraemia. The hyponatraemic group had a median estimated fluid intake on the day of testing that was almost double that of the normal sodium group (6L vs 3.3L). Conclusion: Exercise-associated hyponatraemia occurs in trekkers on the Kokoda Trail. Strategies for prevention of exercise-associated hyponatraemia should be delivered to trekkers via the trekking companies, chiefly focussing on only drinking in response to thirst.</p