Application of Incident Command Structure to clinical trial management in the academic setting: principles and lessons learned

Background Clinical trial success depends on appropriate management, but practical guidance to trial organisation and planning is lacking. The Incident Command System (ICS) is the ‘gold standard’ management system developed for managing diverse operations in major incident and public health arenas. It enables effective and flexible management through integration of personnel, procedures, resources, and communications within a common hierarchical organisational structure. Conventional ICS organisation consists of five function modules: Command, Planning, Operations, Logistics, and Finance/Administration. Large clinical trials will require a separate Regulatory Administrative arm, and an Information arm, consisting of dedicated data management and information technology staff. We applied ICS principles to organisation and management of the Prehospital Use of Plasma in Traumatic Haemorrhage (PUPTH) trial. This trial was a multidepartmental, multiagency, randomised clinical trial investigating prehospital administration of thawed plasma on mortality and coagulation response in severely injured trauma patients. We describe the ICS system as it would apply to large clinical trials in general, and the benefits, barriers, and lessons learned in utilising ICS principles to reorganise and coordinate the PUPTH trial. Results Without a formal trial management structure, early stages of the trial were characterised by inertia and organisational confusion. Implementing ICS improved organisation, coordination, and communication between multiple agencies and service groups, and greatly streamlined regulatory compliance administration. However, unfamiliarity of clinicians with ICS culture, conflicting resource allocation priorities, and communication bottlenecks were significant barriers. Conclusions ICS is a flexible and powerful organisational tool for managing large complex clinical trials. However, for successful implementation the cultural, psychological, and social environment of trial participants must be accounted for, and personnel need to be educated in the basics of ICS

A survey of stress, burnout and well-being in UK dentists

Introduction It is well established that dentistry is a stressful profession, primarily due to the nature and working conditions in the dental surgery. With dramatic changes taking place in the profession in recent years it is important to establish the impact this has on dentists' well-being. Aims To determine the levels of stress and burnout in UK dentists and how this relates to well-being and identify the sources of work-related stress dentists report in different fields of practice. Materials and method An online survey comprising of validated measures examining stress, burnout and well-being in dentists was administered to British Dental Association (BDA) members and non-members. Results Valid responses were received from 2053 respondents. Dentists working in the UK exhibit high levels of stress and burnout and low well-being. General dental practitioners (GDPs) seem to be particularly affected. Issues relating to regulation and fear of litigation were deemed to be the most stressful aspects of being a dentist. Conclusions The findings from this study build upon existing research showing that dentistry is a stressful profession. The sources of this stress appear to have shifted over the years, highlighting the changing landscape of dentistry. Interventions should focus on addressing these stressors by making changes to the working conditions of dentists

Prehospital use of plasma in traumatic hemorrhage (The PUPTH Trial): study protocol for a randomised controlled trial

Background Severe traumatic injury and haemorrhagic shock are frequently associated with disruptions of coagulation function (such as trauma-induced coagulopathy TIC) and activation of inflammatory cascades. These pathologies may be exacerbated by current standard of care resuscitation protocols. Observational studies suggest early administration of plasma to severely-injured haemorrhaging patients may correct TIC, minimise inflammation, and improve survival. The proposed randomised clinical trial will evaluate the clinical effectiveness of pre-hospital plasma administration compared with standard- of-care crystalloid resuscitation in severely-injured patients with major traumatic haemorrhage. Methods/design This is a prospective, randomized, open-label, non-blinded trial to determine the effect of pre-hospital administration of thawed plasma (TP) on mortality, morbidity, transfusion requirements, coagulation, and inflammatory response in severely-injured bleeding trauma patients. Two hundred and ten eligible adult trauma patients will be randomised to receive either two units of plasma, to be administered in-field, vsstandard of care normal saline (NS). Main analyses will compare subjects allocated to TP to those allocated to NS, on an intention-to-treat basis. Primary outcome measure is all-cause 30-day mortality. Secondary outcome measures include coagulation and lipidomic/pro-inflammatory marker responses, volume of resuscitation fluids (crystalloid, colloid) and blood products administered, and major hospital outcomes (e.g. incidence of MSOF, length of ICU stay, length of hospital stay). Discussion This study is part of a US Department of Defense (DoD)-funded multi-institutional investigation, conducted independently of, but in parallel with, the University of Pittsburgh and University of Denver. Demonstration of significant reductions in mortality and coagulopathic/inflammatory-related morbidities as a result of pre-hospital plasma administration would be of considerable clinical importance for the management of haemorrhagic shock in both civilian and military populations. Trial registration ClinicalTrials.gov: NCT02303964 on 28 November 201

Research Techniques Made Simple: Analysis of Autophagy in the Skin.

Autophagy is required for normal skin homeostasis and its disordered regulation is implicated in a range of cutaneous diseases. Several well-characterized biomarkers of autophagy are used experimentally to quantify autophagic activity or clinically to correlate autophagy with disease progression. This article discusses the advantages and limitations of different approaches for measuring autophagy as well as the techniques for modulating autophagy. These include analysis of endogenous LC3, a central autophagy regulatory protein, and measurement of LC3 flux using a dual-fluorescent reporter, which provides a quantitative readout of autophagy in cell culture systems in vitro and animal models in vivo. Degradation of SQSTM1/p62 during autophagy is proposed as an alternative biomarker allowing the analysis of autophagy both experimentally and clinically. However, the complex regulation of individual autophagy proteins and their involvement in multiple pathways means that several proteins must be analyzed together, preferably over a time course to accurately interpret changes in autophagic activity. Genetic modification of autophagy proteins can be used to better understand basic autophagic mechanisms contributing to health and disease, whereas small molecule inhibitors of autophagy regulatory proteins, lysosomal inhibitors, or activators of cytotoxic autophagy have been explored as potential treatments for skin disorders where autophagy is defective. [Abstract copyright: Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Obsessive Compulsive Treatment Efficacy Trial (OCTET) comparing the clinical and cost effectiveness of self-managed therapies: study protocol for a randomised controlled trial

Background: UK National Institute of Health and Clinical Excellence guidelines for obsessive compulsive disorder (OCD) specify recommendations for the treatment and management of OCD using a stepped care approach. Steps three to six of this model recommend treatment options for people with OCD that range from low-intensity guided self-help (GSH) to more intensive psychological and pharmacological interventions. Cognitive behavioural therapy (CBT), including exposure and response prevention, is the recommended psychological treatment. However, whilst there is some preliminary evidence that self-managed therapy packages for OCD can be effective, a more robust evidence base of their clinical and cost effectiveness and acceptability is required. Methods/Design: Our proposed study will test two different self-help treatments for OCD: 1) computerised CBT (cCBT) using OCFighter, an internet-delivered OCD treatment package; and 2) GSH using a book. Both treatments will be accompanied by email or telephone support from a mental health professional. We will evaluate the effectiveness, cost and patient and health professional acceptability of the treatments. Discussion: This study will provide more robust evidence of efficacy, cost effectiveness and acceptability of self-help treatments for OCD. If cCBT and/or GSH prove effective, it will provide additional, more accessible treatment options for people with OCD

Optical and infrared observations of the Crab Pulsar and its nearby knot

We study the spectral energy distribution (SED) of the Crab Pulsar and its nearby knot in the optical and in the infrared (IR) regime. We present high-quality UBVRIz, as well as adaptive optics JHK_sL' photometry, achieved under excellent conditions with the FORS1 and NAOS/CONICA instruments at the VLT. We combine these data with re-analyzed archival Spitzer Space Telescope data to construct a SED for the pulsar, and quantify the contamination from the knot. We have also gathered optical imaging data from 1988 to 2008 from several telescopes in order to examine the predicted secular decrease in luminosity. For the Crab Pulsar SED we find a spectral slope of alpha_nu = 0.27+-0.03 in the optical/near-IR regime, when we exclude the contribution from the knot. For the knot itself, we find a much redder slope of alpha_nu = -1.3 +- 0.1. Our best estimate of the average decrease in luminosity for the pulsar is 2.9+-1.6 mmag per year. We have demonstrated the importance of the nearby knot in precision measurements of the Crab Pulsar SED, in particular in the near-IR. We have scrutinized the evidence for the traditional view of a synchrotron self-absorption roll-over in the infrared, and find that these claims are unfounded. We also find evidence for a secular decrease in the optical light for the Crab Pulsar, in agreement with current pulsar spin-down models. However, although our measurements of the decrease significantly improve on previous investigations, the detection is still tentative. We finally point to future observations that can improve the situation significantly.Comment: For publication in A&

On the metallicity dependence of HMXBs

It is commonly assumed that high mass X-ray binary (HMXB) populations are little-affected by metallicity. However, the massive stars making up their progenitor systems depend on metallicity in a number of ways, not least through their winds. We present simulations, well-matched to the observed sample of Galactic HMXBs, which demonstrate that both the number and the mean period of HMXB progenitors can vary with metallicity, with the number increasing by about a factor of three between solar and SMC metallicity. However, the SMC population itself cannot be explained simply by metallicity effects; it requires both that the HMXBs observed therein primarily sample the older end of the HMXB population, and that the star formation rate at the time of their formation was very large.Comment: 13 pages, 6 figures, MNRAS accepte

‘The opportunity to have their say’? Identifying mechanisms of community engagement in local alcohol decision-making

Background Engaging the community in decisions-making is recognised as important for improving public health, and is recommended in global alcohol strategies, and in national policies on controlling alcohol availability. Yet there is little understanding of how to engage communities to influence decision-making to help reduce alcohol-related harms. We sought to identify and understand mechanisms of community engagement in decision-making concerning the local alcohol environment in England. Methods We conducted case studies in three local government areas in England in 2018, purposively selected for examples of community engagement in decisions affecting the local alcohol environment. We conducted 20 semi-structured interviews with residents, workers, local politicians and local government practitioners, and analysed documents linked to engagement and alcohol decision-making. Results Four rationales for engaging the community in decision-making affecting the alcohol environment were identified: i) as part of statutory decision-making processes; ii) to develop new policies; iii) as representation on committees; and iv) occurring through relationship building. Many of the examples related to alcohol licensing processes, but also local economy and community safety decision-making. The impact of community inputs on decisions was often not clear, but there were a few instances of engagement influencing the process and outcome of decision-making relating to the alcohol environment. Conclusions While influencing statutory licensing decision-making is challenging, community experiences of alcohol-related harms can be valuable ‘evidence’ to support new licensing policies. Informal relationship-building between communities and local government is also beneficial for sharing information about alcohol-related harms and to facilitate future engagement. However, care must be taken to balance the different interests among diverse community actors relating to the local alcohol environment, and extra support is needed for those with least capacity to engage but who face more burden of alcohol-related harms, to avoid compounding existing inequalities