Paul Rees

Clinical features and viral kinetics in a rapidly cured patient with Ebola virus disease: a case report

BACKGROUND A detailed description of viral kinetics, duration of virus shedding, and intraviral evolution in different body sites is warranted to understand Ebola virus pathogenesis. Patients with Ebola virus infections admitted to university hospitals provide a unique opportunity to do such in-depth virological investigations. We describe the clinical, biological, and virological follow-up of a case of Ebola virus disease. METHODS A 43-year-old medical doctor who contracted an Ebola virus infection in Sierra Leone on Nov 16, 2014 (day 1), was airlifted to Geneva University Hospitals, Geneva, Switzerland, on day 5 after disease onset. The patient received an experimental antiviral treatment of monoclonal antibodies (ZMAb) and favipiravir. We monitored daily viral load kinetics, estimated viral clearance, calculated the half-life of the virus in plasma, and analysed the viral genome via high-throughput sequencing, in addition to clinical and biological signs. FINDINGS The patient recovered rapidly, despite an initial high viral load (about 1 × 10(7) RNA copies per mL 24 h after onset of fever). We noted a two-phase viral decay. The virus half-life decreased from about 26 h to 9·5 h after the experimental antiviral treatment. Compared with a consensus sequence of June 18, 2014, the isolate that infected this patient displayed only five synonymous nucleotide substitutions on the full genome (4901A→C, 7837C→T, 8712A→G, 9947T→C, 16201T→C) despite 5 months of human-to-human transmission. INTERPRETATION This study emphasises the importance of virological investigations to fully understand the course of Ebola virus disease and adaptation of the virus. Whether the viral decay was caused by the effects of the immune response alone, an additional benefit from the antiviral treatment, or a combination of both is unclear. In-depth virological analysis and randomised controlled trials are needed before any conclusion on the potential effect of antiviral treatment can be drawn. FUNDING Geneva University Hospitals, Swiss Office of Public Health, Swiss Agency for Development and Cooperation, and Swiss National Science Foundation.

The mitochondrial permeability transition pore as a target for cardioprotection in hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy, and is the leading cause of sudden cardiac death in the young and a major cause of heart failure [1]. Numerous studies have shown that myocardial ischemia caused by an inability to increase myocardial blood flow (MBF) during stress contribute to the pathophysiology of HCM and are associated with adverse left ventricular (LV) remodelling and systolic dysfunction [1]. Numerous studies have shown that myocardial ischemia, which is caused by an inability to increase myocardial blood flow (MBF) during stress, contributes to the pathophysiology of HCM and is associated with adverse left ventricular (LV) remodelling and systolic dysfunction. In this regard the opening of the mitochondrial permeability transition pore (MPTP) at the onset of reperfusion is a critical determinant of cardiomyocyte death following myocardial ischaemiareperfusion injury (IRI) [2, 3]. Pharmacological inhibition of MPTP opening at the onset of reperfusion, using agents such as ciclosporin-A (CsA), has been reported to reduce myocardial infarct (MI) size in animal models of IRI [4]. Importantly, MPTP inhibition at the time of myocardial reperfusion has been demonstrated to protect human atrial cardiomyocytes and trabeculae, harvested from patients undergoing coronary artery bypass graft (CABG) surgery, against simulated IRI [5]. Furthermore, CsA has been reported to be reduce MI size in patients when administered at the time of myocardial reperfusion [6, 7]. MPTP inhibition can also be achieved by pharmacologically activating pro-survival kinases such as Akt and Erk1/2 using the HMG Co-A reductase inhibitor, atorvastatin [8]. Experimental animal studies have demonstrated a reduction in MI size with the administration of atorvastatin at reperfusion in both animal and human heart tissue models of simulated IRI [8, 9]. Whilst these cardioprotective mechanisms are known to operate in the setting of “normal” myocardium, little is understood about potential cardioprotective signaling pathways in HCM. The ability of pharmacological agents to inhibit MPTP opening as a strategy for limiting myocardial IRI, may provide a novel therapeutic intervention for patients with HCM. Therefore, in the current study, the overall objective was to demonstrate the MPTP to be a viable target for cardioprotection in patients with HCM.

Enhanced case management can be delivered for patients with EVD in Africa: Experience from a UK military Ebola treatment centre in Sierra Leone

Highlights • EVD is associated with life-threatening electrolyte imbalance and organ dysfunction.• Clinical staging/early warning scores can be useful EVD prognostic indicators.• Enhanced protocolized care is a blueprint for future treatment in low-resource settings.

Coronary artery disease in the military patient

Ischaemic heart disease is the most common cause of sudden death in the UK, and the most common cardiac cause of medical discharge from the Armed Forces. This paper reviews current evidence pertaining to the diagnosis and management of coronary artery disease from a military perspective, encompassing stable angina and acute coronary syndromes. Emphasis is placed on the limitations inherent in the management of acute coronary syndromes in the deployed environment. Occupational issues affecting patients with coronary artery disease are reviewed. Consideration is also given to the potential for coronary artery disease screening in the military, and the management of modifiable cardiovascular disease risk factors, to help decrease the prevalence of coronary artery disease in the military population.

Nurse delivered focused echocardiography to determine intravascular volume status in a deployed maritime critical care unit

Focused echocardiography is increasingly used by clinicians to guide fluid resuscitation. The UK Defence Medical Services (DMS) have adopted focused echocardiography as a tool to guide flow assessment and resuscitation in deployed critical care. We aimed to explore whether two focused echo techniques, namely Inferior Vena Cava (IVC) and Left Ventricular Outflow Tract Velocity Time integer (LVOT VTi) respiratory variability could be taught to a group of critical care nurses without previous exposure to ultrasound imaging. After a five-week program of training, validation was carried out on healthy volunteers. The mentor, an accredited focused echo trainer, and six nurses performed a total of forty-eight scans on eleven volunteers. The mentor and students acquired subcostal long axis views of the IVC and apical five chamber views using a high frequency linear ultrasound probe. Mean values from three measurements were obtained for IVC diameter and LVOT VTi. Minimum and maximum values were recorded for both variables across a full respiratory cycle. Echo images were saved and at least two images for each student were reviewed offline by an accredited echo-training supervisor. In all cases students were able to obtain adequate echo windows. There was good correlation between values recorded by the mentor and students for both IVC diameter (r = 0.90, p < 0.001) and LVOT VTi (r = 0.77, p < 0.001). Bland Altman analysis showed good correlation with minimal bias for VTi measurements. There was some increase in bias for IVC measurements below 1.2 cm. In summary, we found that these skills for assessing intravascular volume status could be acquired in a relatively short time by specialist nurses without previous experience, and that results were comparable to those produced by an experienced practitioner.

REBOA at Role 2 Afloat: resuscitative endovascular balloon occlusion of the aorta as a bridge to damage control surgery in the military maritime setting

Role 2 Afloat provides a damage control resuscitation and surgery facility in support of maritime, littoral and aviation operations. Resuscitative endovascular balloon occlusion of the aorta (REBOA) offers a rapid, effective solution to exsanguinating haemorrhage from pelvic and non-compressible torso haemorrhage. It should be considered when the patient presents in a peri-arrest state, if surgery is likely to be delayed, or where the single operating table is occupied by another case. This paper will outline the data in support of endovascular haemorrhage control, describe the technique and explore how REBOA could be delivered using equipment currently available in the Royal Navy Role 2 Afloat equipment module. Also discussed are potential future directions in endovascular resuscitation.

Ebola virus disease managed with blood product replacement and point of care tests in Sierra Leone

Learning Point for Clinicians 1. Blood product transfusion and point-of-care tests can be safely and successfully used in Ebola virus disease (EVD) in resource-constrained settings. 2. Significant coagulopathy and haemorrhage in EVD is not always a pre-terminal event and patients can survive with advanced supportive care. A 28-year-old nurse presented to the Kerry Town Ebola Virus Disease Treatment Unit (EVDTU) in Sierra Leone on Day 5 of his illness with a positive Ebola Virus reverse transcriptase polymerase chain reaction (RT-PCR) test result, made on Day 3 at his employing hospital. His presenting symptoms included malaise, headache, sore throat, nausea and diarrhoea. Initial examination findings demonstrated a fever of 39°C and mild epigastric tenderness but was otherwise unremarkable. A rapid malaria test was negative. Although the EVDTU has a …

Balloon-assisted tracking during primary percutaneous coronary intervention

Abstract Radial artery spasm is one of the most commonly encountered problems during transradial interventions with a reported incidence in the range of 6–10%. Balloon-assisted tracking (BAT) of guide catheter has recently been described as a novel technique to overcome difficult radial artery anatomies including tortuosity, loops and spasm. In this report, we describe the successful use of BAT in a patient with radial artery spasm during primary angioplasty.

Shocking the system: AEDs in military resuscitation

Automated external defibrillator (AED) devices have been in routine clinical use since the early 1990s to deliver life-saving shocks to appropriate patients in non-clinical environments. As expectations of survival from out-of-hospital cardiac arrest increase, and evidence incontrovertibly points to reduced timelines as the most crucial factor in achieving return of spontaneous circulation, questions regarding the availability and location of AEDs in the UK military need to be readdressed. This article explores the background of AEDs and reviews their history, life-saving potential and defines current and best practice. It goes on to review the evidence surrounding training and looks to identify knowledge gaps that might be addressed effectively by future research. Finally, it makes recommendations regarding training, availability of AEDs on military bases and locations most likely to deliver good outcomes for military personnel in the future.

Acute chest pain in contingency operations at a Role 1 facility

Acute chest pain is a common medical presenting complaint which can be difficult to diagnose and treat outside of a fully equipped emergency department. In future contingency operations the number of personnel deployed is likely be smaller, with the medical cover appropriate for the population at risk, such that the deployed medical facilities will be smaller than the Role 3 unit with which we have become familiar over the last 10 years of operations in Afghanistan. Physician involvement in these smaller medical facilities is crucial to maintain clinical effect when dealing with patients presenting with disease and non-battle injury, which can often make up the majority of deployed healthcare work. Patients presenting with chest pain require rapid assessment and stabilisation prior to medical evacuation to a suitable definitive care unit. This article focuses on emergency acute chest pain presentations, non-cardiac causes of chest pain, risk reduction and how contingency will affect patient care.