Establishment of a core outcome set for burn care research: development and international consensus.

Objective: To develop a core outcome set for international burn research. Design: Development and international consensus, from April 2017 to November 2019. Methods: Candidate outcomes were identified from systematic reviews and stakeholder interviews. Through a Delphi survey, international clinicians, researchers, and UK patients prioritised outcomes. Anonymised feedback aimed to achieve consensus. Pre-defined criteria for retaining outcomes were agreed. A consensus meeting with voting was held to finalise the core outcome set. Results: Data source examination identified 1021 unique outcomes grouped into 88 candidate outcomes. Stakeholders in round 1 of the survey, included 668 health professionals from 77 countries (18% from low or low middle income countries) and 126 UK patients or carers. After round 1, one outcome was discarded, and 13 new outcomes added. After round 2, 69 items were discarded, leaving 31 outcomes for the consensus meeting. Outcome merging and voting, in two rounds, with prespecified thresholds agreed seven core outcomes: death, specified complications, ability to do daily tasks, wound healing, neuropathic pain and itch, psychological wellbeing, and return to school or work. Conclusions: This core outcome set caters for global burn research, and future trials are recommended to include measures of these outcomes.

Evaluation of high protein intake to improve clinical outcome and nutritional status for patients with burns: a systematic review.

BACKGROUND AND AIM: Patients with severe burns undergo a local and systemic response to the injury. As part of this response the patient becomes hypermetabolic. Current guidelines advise high protein intakes to counteract the catabolic response to burns, but this appears to be based on minimal experimental evidence. Hence the aim of this review was to examine the evidence for improvements in nutritional status and clinical outcome with the administration of high protein intakes for patients with burns. METHODS: Eight databases were searched for clinical trials with burn patients receiving two or more levels of protein intake at or above the level recommended for healthy individuals (0.75g/kg/d) and presenting results for at least one of the following pre-defined outcomes: nitrogen balance, length of stay, weight change, survival, physical therapy index, protein fractional synthetic rate, immunological measurements, bacteraemic days, systemic antibiotic days and net protein synthesis. RESULTS: Six studies were included, 4 of which were randomized trials. All had major methodological limitations, in particular none was blinded. There was too much heterogeneity in study design, patient characteristics and the timing and magnitude of the interventions to justify formal meta-analysis. There was no reliable evidence of improvement in nitrogen balance, but there was some evidence of increased weight gain on higher protein diets. One small study reported an increase in survival and significant improvements in infection rates and some indicators of immune function in children. Length of stay was not significantly improved. There was weak evidence of an improvement in muscle strength and endurance but no significant increase in protein synthesis in muscle or skin, or net protein synthesis in the whole body. CONCLUSION: There is currently only very weak evidence to justify administering high protein diets to patients following burns.

Protocol for the development of a core indicator set for reporting burn wound infection in trials: ICon-B study.

INTRODUCTION: Systematic reviews of high-quality randomised controlled trials are necessary to identify effective interventions to impact burn wound infection (BWI) outcomes. Evidence synthesis requires that BWI is reported in a consistent manner. Cochrane reviews investigating interventions for burns report that the indicators used to diagnose BWI are variable or not described, indicating a need to standardise reporting. BWI is complex and diagnosed by clinician judgement, informed by patient-reported symptoms, clinical signs, serum markers of inflammation and bacteria in the wound. Indicators for reporting BWI should be important for diagnosis, frequently observed in patients with BWI and assessed as part of routine healthcare. A minimum (core) set of indicators of BWI, reported consistently, will facilitate evidence synthesis and support clinical decision-making. AIMS: The Infection Consensus in Burns study aims to identify a core indicator set for reporting the diagnosis of BWI in research studies. METHODS: (1) Evidence review: a systematic review of indicators used in trials and observational studies reporting BWI outcomes to identify a long list of candidate indicators; (2) refinement of the long list into a smaller set of survey questions with an expert steering group; (3) a two-round Delphi survey with 100 multidisciplinary expert stakeholders, to achieve consensus on a short list of indicators; (4) a consensus meeting with expert stakeholders to agree on the BWI core indicator set. ETHICS AND DISSEMINATION: Participants will be recruited through professional bodies, such that ethical approval from the National Health Service (NHS) Health Research Authority (HRA) is not needed. The core indicator set will be disseminated through peer-reviewed publication, co-production with journal editors, research funders and professional bodies, and presentation at national conferences. PROSPERO REGISTRATION NUMBER: CRD42018096647.

Genetic influence on scar height and pliability after burn injury in individuals of European ancestry: A prospective cohort study.

After similar extent of injury there is considerable variability in scarring between individuals, in part due to genetic factors. This study aimed to identify genetic variants associated with scar height and pliability after burn injury. An exome-wide array association study and gene pathway analysis were performed on a prospective cohort of 665 patients treated for burn injury. Outcomes were scar height (SH) and scar pliability (SP) sub-scores of the modified Vancouver Scar Scale (mVSS). DNA was genotyped using the Infinium® HumanCoreExome-24 BeadChip. Associations between genetic variants (single nucleotide polymorphisms) and SH and SP were estimated using an additive genetic model adjusting for age, sex, number of surgical procedures and % total body surface area of burn in subjects of European ancestry. No individual genetic variants achieved the cut-off threshold of significance. Gene regions were analysed for spatially correlated single nucleotide polymorphisms and significant regions identified using comb-p software. This gene list was subject to gene pathway analysis to find which biological process terms were over-represented. Using this approach biological processes related to the nervous system and cell adhesion were the predominant gene pathways associated with both SH and SP. This study suggests genes associated with innervation may be important in scar fibrosis. Further studies using similar and larger datasets will be essential to validate these findings.

Neurosurgical transection of the breast: an unexpected extracranial complication of ventriculoperitoneal shunt insertion.

Ventriculoperitoneal (VP) shunt placement is among the most common surgical procedures undertaken by neurosurgeons. Complications arising from the thoracic portion of the shunt are relatively rare in comparison with those of the intraventricular and peritoneal portions. Disruption of primary breast development following VP shunt placement has not previously been reported. The authors describe the case of a 15-year-old girl referred to the plastic surgery department with a significant right breast deformity and associated asymmetry following VP shunt placement performed during the neonatal period. The calcified shunt was excised and the breast deformity was corrected surgically through multiple scar tissue releases and restoration of the normal breast parenchymal anatomy via a minimally invasive approach, resulting in an excellent aesthetic outcome. This case highlights the potential for injury to occult breast tissue in pediatric patients undergoing VP shunt placement, which can impair subsequent cosmesis and quality of life.

Ethnic differences in burn mechanism and severity in a UK paediatric population.

BACKGROUND: Burns in children are a major public health problem with long-lasting physical and psychological sequelae. Previous studies have identified that children from ethnic minorities have higher rates of burns. OBJECTIVE: The purpose of this study was to analyse the differences in paediatric burn mechanism and severity within different ethnic groups. METHODS: Demographic and burn data from all paediatric patients presenting with burn at the Burns Service, Alder Hey Children's NHS Foundation Trust, Liverpool, UK were collected over a 5 year period. RESULTS: 766 paediatric patients (age range: 7 days to 16 years old, mean: 4.5 years) were included in the study. Ethnic minority children had higher total body surface area of burn (p<0.001) and length of stay (p<0.001) compared with non-ethnic minority children. Chinese children had most burns from hot food (60%), whereas non-ethnic minority children had most burns from hot beverages (35.8%). Ethnic minority children were more deprived compared with non-ethnic minority children (Index of Multiple Deprivation 48.7 vs. 40.9; p=0.02). CONCLUSION: These results show that there are significant differences in the patterns of burns in ethnic minority groups. This data should guide targeted public health prevention and educational strategies.

Burn disasters--an audit of the literature.

All events that result in disasters are unique, and it is impossible to become fully prepared. However, through thorough planning and preparedness, it is possible to gain a better understanding of the typical injury patterns and problems that arise from a variety of hazards. Such events have the potential to claim many lives and overwhelm local medical resources. Burn disasters vary in scope of injury and procedures required, and are much more labor and resource intensive than non-burn disasters. This review of the literature should help determine whether, despite each event having its own unique features, there still are common problems disaster responders face in the prehospital and hospital phases, what recommendations were made from these disasters, and whether these recommendations have been implemented into practice and the current disaster planning processes. The objective of this review was to assess: (1) prehospital and hospital responses used during past burn disasters; (2) problems faced during those disaster responses; (3) recommendations made following those disasters; (4) whether these recommendations were integrated into practice; and (5) the key characteristics of burn disasters and how they differ from other disasters. This review is important to determine why, despite having disaster plans, things still go wrong.

Thiamine supplementation increases serum thiamine and reduces pyruvate and lactate levels in burn patients.

The importance of vitamins for optimal metabolism is well established. However, currently little is known about the optimal vitamin levels required for burn patients. As a consequence, current practice both for macronutrient supplementation and vitamin supplementation varies widely between burn units. A better understanding of the effects of vitamins on metabolism may lead to better nutrition and subsequently improved outcomes for burn patients. Thiamine is an important co-factor required for multiple enzymes involved in carbohydrate metabolism. We have examined the levels of thiamine (B1) in burn patients as well as the effects of thiamine supplementation on the levels of serum thiamine, pyruvate and lactate. Twenty patients had blood samples taken on the day of admission, then on days 1, 3, and 7 post-admission and weekly thereafter until discharge. Of these, nine received enteral feeding. Six patients received thiamine supplementation. Serum thiamine, pyruvate and lactate levels were measured at each time point. Serum thiamine levels increased significantly with thiamine supplementation (p<0.001). Serum thiamine levels also increased with time of supplementation (p<0.001). Serum thiamine level was closely associated with pyruvate and lactate levels, with a decrease in both pyruvate and lactate associated with increased serum thiamine. Lastly, pyruvate and lactate levels appear closely associated in a linear relationship. This study suggests thiamine supplementation increases serum thiamine and that this increase is associated with a decrease in pyruvate and lactate levels. Further study of changes in metabolic flux associated with thiamine supplementation and a randomised control trial of thiamine supplementation are required to establish whether thiamine supplementation is beneficial to burn patients' metabolism and recovery.

Core outcomes for adult burn survivors: a clinical overview.

Burn trauma ranges from the minor burn to the devastating injury, which can impact on all aspects of a person's life including aesthetic appearance, relationships with others and psychological, social and physical functioning. Measurement of outcome in burns patients is therefore complex and multi-faceted. The increasing numbers of major burn survivors implies that understanding health outcomes in these patients has assumed high priority. This paper sets out a conceptual framework for unifying outcome measurement, which may be useful to all members of the multidisciplinary team who are contemplating outcome assessment in their burn patients. It outlines seven core domains of assessment which are (i) skin; (ii) neuromuscular function; (iii) sensory and pain; (iv) psychological function; (v) physical role function; (vi) community participation; and (vii) perceived quality of life. Within each domain, we present a brief clinical review of the most commonly administered measurement tools that have been, or potentially could be, used to assess aspects of these core domains. Where possible, the psychometric properties and clinical utility of these tools are presented. A concise discussion of key methodological issues which should be addressed in this assessment process is then provided, together with suggestions for future research.

Exogenous metallothionein-IIA promotes accelerated healing after a burn wound.

Severe injury to the epidermal barrier often results in scarring and life-long functional deficits, the outcome worsening with a number of factors including time taken to heal. We have investigated the potential of exogenous metallothionein IIA (Zn(7)-MT-IIA), a naturally occurring small cysteine-rich protein, to accelerate healing of burn wounds in a mouse model. Endogenous MT-I/II expression increased in basal keratinocytes concurrent with reepithelialization after a burn injury, indicating a role for MT-I/II in wound healing. In vitro assays of a human keratinocyte cell line indicated that, compared with saline controls, exogenous Zn(7)-MT-IIA significantly increased cell viability by up to 30% (p<0.05), decreased apoptosis by 13% (p<0.05) and promoted keratinocyte migration by up to 14% (p<0.05), all properties that may be desirable to promote rapid wound repair. Further in vitro assays using immortalized and primary fibroblasts indicated that Zn7-MT-IIA did not affect fibroblast motility or contraction (p>0.05). Topical administration of exogenous Zn(7)-MT-IIA (2 microg/mL) in vivo, immediately postburn accelerated healing, promoted faster reepithelialization (3 days: phosphate-buffered saline (PBS), 8.9+/-0.3 mm diameter vs. MT-I/II, 7.1+/-0.7 mm; 7 days: PBS 5.8+/-0.98 mm vs. MT-I/II, 3.6+/-1.0 mm, p<0.05) and reduced epidermal thickness (MT-I/II: 45+/-4 microm vs. PBS: 101+/-19 microm, p<0.05) compared with controls. Our data suggest that exogenous Zn(7)-MT-IIA may prove a valuable therapeutic for patients with burns and other skin injuries.