Quantifying the clinical and economic burden of desquamating dermatological conditions: Implications for a supraregional burns centre.

INTRODUCTION: This study aimed to identify the spectrum of desquamating skin diseases referred for tertiary burns care and quantify the care requirements and expenses associated with caring for these patients within the burns service. METHODS: Patient records were identified with nonburn-induced skin loss between 2016 and 2022. Data was extracted from inpatient records, operative notes, and dressing clinic records. A cost analysis was conducted using figures from the National Schedule of National Health Service Costs and our own unit-specific costs. RESULTS: Twenty patients were identified, with a median age of 46.5 and a median total body surface area of 30%. The mean length of stay was 21.2 days, with 8/20 patients requiring intensive care. Overall mortality was 30%, rising to 50% if patients required intensive treatment unit (ITU) admission. Patients had a mean of 1.5 procedures under general anaesthesia and a mean operative time of 169 min per patient. Postoperatively, a mean of 8.3 dressing changes was required per patient (range 1-21). Of 75% of patients referred as suspected toxic epidermal necrolysis syndrome (TENS), only 32% of patients histologically had TENS (32%), with linear IgA disease, pemphigus vulgaris and bullous lupus comprising the other diagnoses. Cost analysis predicted a total cost to the unit of £1,422,106. CONCLUSION: Desquamating dermatological diseases are life-threatening conditions with exhaustive care requirements. Our experiences highlight the importance of awareness of the range of desquamating skin conditions beyond TENS to enable optimum management and the need to ensure adequate financial provisions to accommodate the care requirements mandated by these patients.

Development of a versatile enzyme immunoassay for non-invasive assessment of glucocorticoid metabolites in a diversity of taxonomic species.

Endocrinology is a useful tool for conservation biologists and animal managers, and measuring glucocorticoids can help understand biological mechanisms associated with species decline and animal welfare. The current study describes the development and optimization of a glucocorticoid enzyme immunoassay (EIA) to non-invasively assess adrenal activity in a variety of taxa. The antiserum (CJM006) was raised in rabbits to a corticosterone-3-CMO-BSA immunogen and used in a standard competitive EIA system. However, the EIA initially produced results with unacceptably high inter-assay variation, attributed to consistent patterns observed within the optical density of developing plates. To determine the cause of this variability, a number of factors were examined using synthetic corticosterone standard and endogenous faecal extract, including: plate type (Nunc MaxiSorp® II versus Immulon IB plates); the use of non-specific secondary antibody; type (artificial versus natural) and presence (light versus dark) of light during incubation; plate loading temperature (4°C versus room temperature); and substrate reagent temperature (4°C versus room temperature). Results indicated that variability was associated with plate location effects, which were not initially detected because control samples were always run in the same positions across plates. Light and temperature were the two major factors that affected EIA reliability. For this assay, the standard protocol required slight modification, with the optimal protocol using Nunc MaxiSorp® plates, room temperature substrate reagents and dark incubation conditions. Following optimization, this EIA was then validated biochemically for 38 species, through parallel displacement curves and interference assessment tests of faecal and urine samples. Additionally, biological validation was performed opportunistically in a subset of species, with use of this EIA demonstrating significant elevations in faecal glucocorticoid metabolites following potentially challenging events. In summary, this glucocorticoid EIA cross-reacts with excreted glucocorticoid metabolites across a wide range of taxa, including ungulates, primates, felids, birds, rodents and amphibians. We conclude that when used with optimal reagent and incubation conditions, this EIA will be useful for non-invasive monitoring of adrenal activity in a wide range of wildlife species.

Gait-specific energetics contributes to economical walking and running in emus and ostriches.

A widely held assumption is that metabolic rate (E(met)) during legged locomotion is linked to the mechanics of different gaits and this linkage helps explain the preferred speeds of animals in nature. However, despite several prominent exceptions, E(met) of walking and running vertebrates has been nearly uniformly characterized as increasing linearly with speed across all gaits. This description of locomotor energetics does not predict energetically optimal speeds for minimal cost of transport (E(cot)). We tested whether large bipedal ratite birds (emus and ostriches) have gait-specific energetics during walking and running similar to those found in humans. We found that during locomotion, emus showed a curvilinear relationship between E(met) and speed during walking, and both emus and ostriches demonstrated an abrupt change in the slope of E(met) versus speed at the gait transition with a linear increase during running. Similar to human locomotion, the minimum net E(cot) calculated after subtracting resting metabolism was lower in walking than in running in both species. However, the difference in net E(cot) between walking and running was less than is found in humans because of a greater change in the slope of E(met) versus speed at the gait transition, which lowers the cost of running for the avian bipeds. For emus, we also show that animals moving freely overground avoid a range of speeds surrounding the gait-transition speed within which the E(cot) is large. These data suggest that deviations from a linear relation of metabolic rate and speed and variations in transport costs with speed are more widespread than is often assumed, and provide new evidence that locomotor energetics influences the choice of speed in bipedal animals. The low cost of transport for walking is probably ecologically important for emus and ostriches because they spend the majority of their active day walking, and thus the energy used for locomotion is a large part of their daily energy budget.

Analysis and integration of developmental neurotoxicity and ancillary data into risk assessment: a case study of dimethoate.

Dimethoate is an organophosphate (OP) pesticide used to control a wide variety of insects on agricultural crops and ornamentals. To ensure that dimethoate is used safely, it is important to determine exposure levels that protect against adverse effects at all life stages, including the developing fetus, infant, and child. Based on an analysis of a developmental neurotoxicity (DNT) study, a cholinesterase (ChE) sensitivity study, a cross-fostering study, and several single- and multigenerational reproductive toxicity studies, two potential critical endpoints for dimethoate were identified: brain ChE inhibition (ChEI) in adult females, and pup mortality. An initial evaluation concluded that pup mortality was a preferable endpoint, based on an increased number of pup deaths born to dams dosed with > or =3 mg/kg dimethoate via oral gavage. Closer examination, however, revealed that the pup deaths were clustered in a small number of litters in which the dams providing postnatal care exhibited maternal care deficits. When the data were analyzed using the dam as the unit of statistical significance, a significant increase in the average litter proportion of pup deaths was observed only when the dams were dosed postnatally with 6 mg/kg dimethoate while they were raising the pups. Gestational exposure (i.e., during pregnancy only) to 6 mg/kg dimethoate exerted no effect on pup survival. This leads to the conclusion that it is postnatal exposure of the nursing dams that is associated with pup mortality. Furthermore, a previous benchmark dose (BMD) meta-analysis approach revealed that BMDL(10) for adult females (the lower 95% bound of the dose resulting in a 10% reduction in the parameter of interest) for ChEI was > 3-fold lower than the BMDL(10) for pup mortality (0.19 and 0.68 mg/kg, respectively). Overall, this study underscores the importance of using the dam as the unit of statistical significance when assessing data collected in the perinatal period, and it is concluded that adult brain ChEI is the correct critical endpoint for assessing risk of dimethoate toxicity.