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

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.

Behavioural drivers influencing emergency department attendance in Victoria during the 2020 COVID-19 pandemic: A mixed methods investigation.

OBJECTIVE: To identify behavioural drivers and barriers that may have contributed to changes in ED attendance during the first 10 months of the coronavirus disease 2019 (COVID-19) pandemic in Victoria. METHODS: We conducted a mixed methods analysis of patients who attended one of eight participating EDs between 1 November 2019 and 31 December 2020. A random sample of patients were chosen after their visit and invited to participate in an online survey assessing behavioural drivers and barriers to attendance. The study timespan was divided into four periods based on local and world events to assess changes in attitudes and behaviours over this period. RESULTS: A total of 5600 patients were invited to complete the survey and 606 (11%) submitted sufficient information for analysis. There were significant differences in participants' attitudes towards healthcare and EDs, levels of concern about contracting and spreading COVID-19 and the influence of mask wearing. Patients expressed more concern about the safety of an ED during the largest outbreak of COVID-19 infections than they did pre-COVID, but this difference was not sustained once community infection numbers dropped. General concerns about hospital attendance were higher after COVID than they were pre-COVID. A total of 27% of patients specifically stated that they had delayed their ED attendance. CONCLUSION: Patients expressed increased concerns around attending ED during the first 10 months of the 2020 COVID-19 pandemic and frequently cited COVID-19 as a reason for delaying their presentation. These factors would be amenable to mitigation via focussed public health messaging.

Compassionate drug (mis)use during pandemics: lessons for COVID-19 from 2009.

BACKGROUND: New emerging infections have no known treatment. Assessing potential drugs for safety and efficacy enables clinicians to make evidence-based treatment decisions and contributes to overall outbreak control. However, it is difficult to launch clinical trials in the unpredictable environment of an outbreak. We conducted a bibliometric systematic review for the 2009 influenza pandemic to determine the speed and quality of evidence generation for treatments. This informs approaches to high-quality evidence generation in this and future pandemics. METHODS: We searched PubMed for all clinical data (including clinical trial, observational and case series) describing treatment for patients with influenza A(H1N1)pdm09 and ClinicalTrials.gov for research that aimed to enrol patients with the disease. RESULTS: Thirty-three thousand eight hundred sixty-nine treatment courses for patients hospitalised with A(H1N1)pdm09 were detailed in 160 publications. Most were retrospective observational studies or case series. Five hundred ninety-two patients received treatment (or placebo) as participants in a registered interventional clinical trial with results publicly available. None of these registered trial results was available during the timeframe of the pandemic, and the median date of publication was 213 days after the Public Health Emergency of International Concern ended. CONCLUSION: Patients were frequently treated for pandemic influenza with drugs not registered for this indication, but rarely under circumstances of high-quality data capture. The result was a reliance on use under compassionate circumstances, resulting in continued uncertainty regarding the potential benefits and harms of anti-viral treatment. Rapid scaling of clinical trials is critical for generating a quality evidence base during pandemics.

Management of adult cardiac arrest in the COVID-19 era: consensus statement from the Australasian College for Emergency Medicine.

INTRODUCTION: The global pandemic of coronavirus disease 2019 (COVID-19) has caused significant worldwide disruption. Although Australia and New Zealand have not been affected as much as some other countries, resuscitation may still pose a risk to health care workers and necessitates a change to our traditional approach. This consensus statement for adult cardiac arrest in the setting of COVID-19 has been produced by the Australasian College for Emergency Medicine (ACEM) and aligns with national and international recommendations. MAIN RECOMMENDATIONS: In a setting of low community transmission, most cardiac arrests are not due to COVID-19. Early defibrillation saves lives and is not considered an aerosol generating procedure. Compression-only cardiopulmonary resuscitation is thought to be a low risk procedure and can be safely initiated with the patient's mouth and nose covered. All other resuscitative procedures are considered aerosol generating and require the use of airborne personal protective equipment (PPE). It is important to balance the appropriateness of resuscitation against the risk of infection. Methods to reduce nosocomial transmission of COVID-19 include a physical barrier such as a towel or mask over the patient's mouth and nose, appropriate use of PPE, minimising the staff involved in resuscitation, and use of mechanical chest compression devices when available. If COVID-19 significantly affects hospital resource availability, the ethics of resource allocation must be considered. CHANGES IN MANAGEMENT: The changes outlined in this document require a significant adaptation for many doctors, nurses and paramedics. It is critically important that all health care workers have regular PPE and advanced life support training, are able to access in situ simulation sessions, and receive extensive debriefing after actual resuscitations. This will ensure safe, timely and effective management of the patients with cardiac arrest in the COVID-19 era.

Core Minimal Datasets to Advance Clinical Research for Priority Epidemic Diseases.

The Ebola virus disease outbreak in west Africa has prompted significant progress in responding to the clinical needs of patients affected by emerging infectious disease outbreaks. Among the noteworthy successes of vaccine trials, and the commendable efforts to implement clinical treatment trials during Ebola outbreaks, we should also focus on strengthening the collection and curation of epidemiological and observational data that can improve the conception and design of clinical research.

Clinical assessment is a neglected component of outbreak preparedness: evidence from refugee camps in Greece.

BACKGROUND: Refugees may have an increased vulnerability to infectious diseases, and the consequences of an outbreak are more severe in a refugee camp. When an outbreak is suspected, access to clinical information is critical for investigators to verify that an outbreak is occurring, to determine the cause and to select interventions to control it. Experience from previous outbreaks suggests that the accuracy and completeness of this information is poor. This study is the first to assess the adequacy of clinical characterisation of acute medical illnesses in refugee camps. The objective is to direct improvements in outbreak identification and management in this vulnerable setting. METHODS: We collected prospective data in 13 refugee camps in Greece. We passively observed consultations where patients presented with syndromes that might warrant inclusion into an existing syndromic surveillance system and then undertook a structured assessment of routine clinical data collection to examine the extent to which key clinical parameters required for an outbreak response were ascertained and then documented. RESULTS: A total of 528 patient consultations were included. The most common presenting condition was an acute respiratory illness. Clinicians often made a comprehensive clinical assessment, especially for common syndromes of respiratory and gastrointestinal conditions, but documented their findings less frequently. For fewer than 5% of patients were a full set of vital signs ascertained and so the severity of patient illnesses was largely unknown. In only 11% of consultations was it verified that a patient who met the case criteria for syndromic surveillance reporting based on an independent assessment was reported into the system. DISCUSSION: Opportunities exist to strengthen clinical data capture and recording in refugee camps, which will produce a better calibrated and directed public health response. CONCLUSION: Information of significant utility for outbreak response is collected at the clinical interface and we recommend improving how this information is recorded and linked into surveillance systems.

Regulatory and Operational Complexities of Conducting a Clinical Treatment Trial During an Ebola Virus Disease Epidemic.

The first phase II and III clinical trials for Ebola virus disease treatments were conducted during the West Africa outbreak. We report the operational practicalities of conducting a phase II clinical trial of TKM-130803 to international standards during this outbreak.

Offering patients more: how the West Africa Ebola outbreak can shape innovation in therapeutic research for emerging and epidemic infections.

Although, after an epidemic of over 28 000 cases, there are still no licensed treatments for Ebola virus disease (EVD), significant progress was made during the West Africa outbreak. The pace of pre-clinical development was exceptional and a number of therapeutic clinical trials were conducted in the face of considerable challenges. Given the on-going risk of emerging infectious disease outbreaks in an era of unprecedented population density, international travel and human impact on the environment it is pertinent to focus on improving the research and development landscape for treatments of emerging and epidemic-prone infections. This is especially the case since there are no licensed therapeutics for some of the diseases considered by the World Health Organization as most likely to cause severe outbreaks-including Middle East respiratory syndrome coronavirus, Marburg virus, Crimean Congo haemorrhagic fever and Nipah virus. EVD, therefore, provides a timely exemplar to discuss the barriers, enablers and incentives needed to find effective treatments in advance of health emergencies caused by emerging infectious diseases.This article is part of the themed issue 'The 2013-2016 West African Ebola epidemic: data, decision-making and disease control'.

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.

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 2 days walk from each end of the Trail. RESULTS: The main outcome measure was hyponatraemia defined as serum sodium level less than 135 mmol/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 (6 L vs 3.3 L). 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.

Heat strain during explosive ordnance disposal.

Bomb technicians perform their work while encapsulated in explosive ordnance disposal suits. Designed primarily for safety, these suits have an unintended consequence of impairing the body's natural mechanisms for heat dissipation. Consequently, bomb technicians are known to experience symptoms of heat illness while performing their work. This research provides the first field based analysis of heat strain in bomb technicians. Six participants undertook simulated operational tasks across 2 days of variable climate. All subjects demonstrated high levels of heat strain as evidenced by elevated heart rate, core body temperature, and physiological strain index. Participants also reported signs and symptoms associated with heat illness. These results were exacerbated by more intense physical activity despite being undertaken in a cooler environment. The universal experience of heat strain in this sample has significant implications for the health of bomb technicians and additional research examining methods to improve temperature regulation and performance is warranted.

The effect of changing limb position on the validity of venous occlusion plethysmography.

Venous occlusion plethysmography (VOP) is a technique used for the non-invasive measurement of limb blood flow. A fundamental technical consideration of venous occlusion plethysmography is that the limb in question must be placed above heart level. However, in light of advances in technology and methodology, the necessity of this has been questioned. We investigated the validity of the VOP technique with the forearm approximately 10 cm above and below the level of the heart in both resting and dynamic conditions. Nine healthy male participants performed four bouts of handgrip exercise, two at each of 15% and 30% maximum voluntary contraction (MVC) (one above and one below the heart). As hypothesized, resting forearm blood flow (FBF) measured below the level of the heart was significantly lower than for above the heart (p = 0.046). However, the opposite occurred during exercise, where FBF measured after the fifth minute of handgrip contractions was significantly higher below the level of the heart (p = 0.013). Furthermore, the ability to accurately quantify FBF below the level of the heart was severely impeded by artifact, and as such VOP appears to remain constricted to use above the phlebostatic level.