Composition and Performance of Autologous Engineered Skin Substitutes for Repair or Regeneration of Excised, Full-Thickness Burns.

Prompt and permanent wound closure after burn injuries remains a requirement for patient recovery. Historically, split-thickness skin autograft (STAG) has served as the prevailing standard of care for closure of extensive, deep burns. Because STAG availability may be insufficient in life-threatening burns, alternatives have been evaluated for safety and efficacy of wound closure. Since the 1970s, alternatives consisting of cultured epidermal keratinocytes, and/or acellular dermal substitutes were studied and translated into services and devices that facilitated wound closure, survival, and recovery after major burns. Cultured epithelial autografts (CEA) promoted epidermal closure of wounds but were not stable during long-term recovery. An acellular dermal substitute consisting of collagen and glycosaminoglycans (C-GAG) provided more uniform dermal repair, and reduced needs for epidermal harvesting but was subject to loss from microbial contamination. More recently, an autologous engineered skin substitute (ESS) has been reported and includes a C-GAG polymer populated with fibroblasts and keratinocytes which form basement membrane. ESS can be applied clinically over a vascularized dermal substitute and generates stable wound closure that is smooth, soft, and strong. Despite these advances, no current alternatives for permanent wound closure restore the anatomy and physiology of uninjured skin. Current alternatives act by mechanisms of wound healing, not by developmental biology by which skin forms in utero with pigment, hair, sweat and sebaceous glands, microvasculature, and nerve. Until full-thickness burns are restored with all of the normal structures and functions of uninjured skin, regenerative medicine of skin will remain an ambitious aspiration for future researchers and engineers to achieve.

Exploring the Past to Inform the Future to Optimize the Pharmacokinetics of Vancomycin in Children With Severe Burn Injuries.

Sepsis remains one of the leading causes of death among pediatric patients with burn injuries. Despite limited vancomycin pharmacokinetic (PK) information within this population, it is widely used to treat severe burn injuries. Those with severe burns are at risk of nephrotoxicity, with an incidence of acute kidney injury (AKI) over 50%. Delivering an effective vancomycin dose and avoiding unnecessary toxicity is essential for improved patient outcomes. This was a retrospective analysis of 115 children aged 0.2 months to 18 years with severe burns, >10% total body surface area. Vancomycin was given via intravenous infusion; blood samples were drawn between 6- and 12-hour postinfusion. A population pharmacokinetic model was developed using nonlinear mixed-effect modeling (Monolix, version 2016R1). A one-compartment model described a steady-state volume of distribution (V), dependent on weight. Vancomycin clearance (CL) was influenced by age and estimated creatinine clearance (CrCL). The study population's (median age = 4 years, median weight = 20 kg, median total body surface area (%TBSA) = 40%) median V and CL were calculated to be 1.25 L/kg (95% CI, 1.04-1.46) and 0.15 L/h/kg (95% CI, 0.126-0.165), respectively. The PK model was explicitly developed to characterize the impact of physiological changes in children under 18 years of age and the percentage of the burn surface area using limited data. The analysis determined that weight, age, and estimated CrCL were important covariates in predicting vancomycin PK with high variability in CL and V.

Impact of Disease on Amikacin Pharmacokinetics and Dosing in Children.

BACKGROUND: Amikacin is widely used to treat severe Gram-negative bacterial infections. Its peak concentration in plasma is associated with treatment efficacy. Amikacin pharmacokinetics (PK) is influenced by disease conditions, in addition to other patient characteristics. In this retrospective study, we evaluated the impact of clinical characteristics and disease condition on amikacin PK in children with burn injuries and those with cancer. METHODS: Amikacin PK data from 66 children with burn injuries and 112 children with cancer were analyzed. A population PK model was developed using the nonlinear mixed-effects modeling approach. Models were developed using NONMEM 7.3 (ICON Development Solutions, LLC, Ellicott City, MD). Data processing and visualization was performed using R packages. RESULTS: The amikacin PK data were best described by a 2-compartment model. The parameters were estimated with mean values (95% confidence intervals) as follows: central volume of distribution (V1), 5.70 L (4.64-6.76 L); central clearance, 2.12 L/h (1.79-2.46 L/h); peripheral volume of distribution (V2), 4.79 L (2.36-7.22 L); and distribution clearance (Q), 0.71 L/h (0.25-1.16 L/h). The final model identified the disease condition as a significant covariate and indicated 55% (28%-82%) higher central clearance and 17% (1%-34%) higher V1 in burn patients compared with cancer patients. Volume of distribution was significantly influenced by age and body weight. Clearance was significantly influenced by age, body weight, and creatinine clearance. Using the final PK model, we developed a workflow for selecting optimal dosing strategies for 3 representative pediatric patient profiles. CONCLUSIONS: Disease condition was significant in influencing amikacin PK in children. To reach the same target concentrations (64 mg/L peak concentration) with a daily-dose plan, burn patients need higher doses than cancer patients. Future investigations are needed to explore the impact of other diseases on amikacin disposition in children, and to prospectively validate the proposed dosing strategy.

Randomized, Paired-Site Comparison of Autologous Engineered Skin Substitutes and Split-Thickness Skin Graft for Closure of Extensive, Full-Thickness Burns.

Stable closure of full-thickness burn wounds remains a limitation to recovery from burns of greater than 50% of the total body surface area (TBSA). Hypothetically, engineered skin substitutes (ESS) consisting of autologous keratinocytes and fibroblasts attached to collagen-based scaffolds may reduce requirements for donor skin, and decrease mortality. ESS were prepared from split-thickness skin biopsies collected after enrollment of 16 pediatric burn patients into an approved study protocol. ESS and split-thickness autograft (AG) were applied to 15 subjects with full-thickness burns involving a mean of 76.9% TBSA. Data consisted of photographs, tracings of donor skin and healed wounds, comparison of mortality with the National Burn Repository, correlation of TBSA closed wounds with TBSA full-thickness burn, frequencies of regrafting, and immunoreactivity to the biopolymer scaffold. One subject expired before ESS application, and 15 subjects received 2056 ESS grafts. The ratio of closed wound to donor areas was 108.7 ± 9.7 for ESS compared with a maximum of 4.0 ± 0.0 for AG. Mortality for enrolled subjects was 6.25%, and 30.3% for a comparable population from the National Burn Repository (P < .05). Engraftment was 83.5 ± 2.0% for ESS and 96.5 ± 0.9% for AG. Percentage TBSA closed was 29.9 ± 3.3% for ESS, and 47.0 ± 2.0% for AG. These values were significantly different between the graft types. Correlation of % TBSA closed with ESS with % TBSA full-thickness burn generated an R value of 0.65 (P < .001). These results indicate that autologous ESS reduce mortality and requirements for donor skin harvesting, for grafting of full-thickness burns of greater than 50% TBSA.

Clinical Trial of Vitamin D2 vs D3 Supplementation in Critically Ill Pediatric Burn Patients.

BACKGROUND: Hypovitaminosis D exists postburn. However, evidence-based guidelines for vitamin D repletion are unknown. This investigation examined differences between D2 and D3 supplementation on outcome in children with burn injuries. METHODS: Fifty patients with total body surface area burn of 55.7% ± 2.6% and full-thickness injury of 40.8% ± 3.8% were enrolled, ranging in age from 0.7-18.4 years. All participants received multivitamin supplementation per standardized clinical protocol. In addition, 100 IU/kg D2, D3, or placebo was administered daily during hospitalization using a randomized, double-blinded study design. Assay of total 25-hydroxyvitamin D (D25), 1,25-dihydroxyvitamin D (D1,25), 25-hydroxyvitamin D2 (25-OH-D2), 25-hydroxyvitamin D3 (25-OH-D3), and parathyroid hormone (PTH) was performed at 4 preplanned time intervals (baseline, midpoint, discharge, and 1 year postburn). Differences in vitamin D status were compared over time and at each specific study interval. RESULTS: There were no significant differences in serum vitamin D levels between groups, but >10% of patients had low D25 at discharge, and percent deficiency worsened by the 1-year follow up for the placebo (75%), D2 (56%), and D3 (25%) groups. There were no statistical differences in PTH or clinical outcomes between treatment groups, although vitamin D supplementation demonstrated nonsignificant but clinically relevant decreases in exogenous insulin requirements, sepsis, and scar formation. CONCLUSIONS: The high incidence of low serum D25 levels 1 year following serious thermal injury indicates prolonged compromise. Continued treatment with vitamin D3 beyond the acute phase postburn is recommended to counteract the trajectory of abnormal serum levels and associated morbidity.

Zolpidem and Sleep in Pediatric Burn Patients with Attention Deficit/Hyperactivity Disorder.

Existing research shows that hospitalized patients, especially pediatric burn patients, are often sleep deprived. A pre-existing diagnosis of attention deficit/hyperactivity disorder (ADHD) further compounds a burn patient's inability to sleep. This retrospective study compared the effectiveness of zolpidem on patients with acute burns with ADHD (n = 23) and patients with acute burns without ADHD (n = 23). Effectiveness was defined based on the need for a change in the sleep medication or an increase in the zolpidem dose during the first 12 days of treatment. This study found that sleep dysfunction was similar in pediatric burn patients with and without a concurrent diagnosis of ADHD. Sixteen (69.6%) patients with and 13 (56.5%) patients without ADHD required a sleep medication change (p = 0.541). Further, while patients with ADHD required a sleep medication change (median = 5 days) sooner than those without ADHD (median = 9 days), it appears that zolpidem is not an effective drug for managing sleep in pediatric burn patients with or without ADHD.

Investigation of Bone Health Subsequent to Vitamin D Supplementation in Children Following Burn Injury.

BACKGROUND: The effect of supplemental vitamin D on fracture occurrence following burn injuries is unclear. The objective of this study was to evaluate postintervention incidence of fractures in children during the rehabilitative phase postburn (PB) following participation in a randomized clinical trial of vitamin D supplementation. MATERIALS AND METHODS: Follow-up for fracture evaluation was obtained in 39 of 50 patients randomized to daily enteral vitamin D2, D3, or placebo throughout the acute burn course. Serum 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, D2, D3, calcitonin, and bone alkaline phosphatase (BAP) measurements were obtained PB day 7, midpoint, discharge, and 1-year PB. Urinary calcium was obtained PB day 7 and midpoint. Dual-energy x-ray absorptiometry (DXA) was performed at discharge and 1-year PB. RESULTS: Fractures were reported in 6 of 39 respondents. Four fractures occurred in the placebo group, 2 in the D2 group, and none in the D3 group. Serum vitamin D, calcitonin, BAP, and urinary calcium were similar between fracture groups. The group with fracture morbidity had larger burn size (83.8% ± 4.9% vs 53.0% ± 2.9%, P < .0001), greater full-thickness burn (69.7% ± 9.4% vs 39.4% ± 4.1%, P = .02), and increased incidence of inhalation injury (33% vs 6%, P = .04). Decreased bone mineral density z score was noted at discharge in the placebo fracture compared with no-fracture group (P < .05). CONCLUSION: This preliminary report suggests there may be benefit of vitamin D3 in reducing postdischarge fracture risk. Results reaffirm the importance of monitoring bone health in pediatric patients postburn.

Clinical safety and efficacy of probiotic administration following burn injury.

Provision of probiotics has been limited postburn by questionable potential for bacterial translocation and risk of infection in an immune-compromised population. The purpose of this study was to evaluate the safety of probiotic administration in acutely burned, pediatric patients. Subjects were randomized to receive probiotic (n = 10) vs placebo (n = 10) twice daily. The investigational product was initiated within 10 days of burn, and daily supplementation continued until wound closure. Nursing staff was provided education regarding optimal procedures to minimize potential for study product cross contamination. Clinical outcomes (infection, antibiotic, antifungal, and operative days, tolerance, and mortality) were recorded. Length of stay was modified for burn size. Student's t-test, χ test, and nonparametric Wilcoxon's rank-sum test were used for comparative analysis. No differences were noted (probiotic; placebo) for age (7.1 ± 2.2; 6.9 ± 1.7), burn size (38.0 ± 5.9; 45.5 ± 4.45), full thickness (24.6 ± 5.6; 32.1 ± 5.4), postburn day admit (0.8 ± 0.4; 1.1 ± 0.4), or inhalation injury (10%; 20%). Infection days, antibiotic use, constipation, and emesis were similar between groups. Trends toward increased antifungal and laxative use as well as diarrhea incidence were evident in the controls (P < .30). Flatulence was statistically higher with probiotics. The control group trended toward higher requirement for excision/graft procedure. Medical length of stay was not significantly different between groups; however, time required to complete wound healing was shortened with probiotics. This study documents safety and provides preliminary efficacy data relative to probiotic supplementation postburn.

Determination of Optimal Amikacin Dosing Regimens for Pediatric Patients With Burn Wound Sepsis.

This study aimed to develop optimal amikacin dosing regimens for the empirical treatment of Gram-negative bacterial sepsis in pediatric patients with burn injuries. A pharmacodynamic (PD) target in which the peak concentration (Cmax) is ≥8 times the minimum inhibitory concentration (MIC) (Cmax/MIC ≥ 8) is reflective of optimal bactericidal activity and has been used to predict clinical outcomes. Population pharmacokinetic modeling was performed in NONMEM 7.2 for pediatric patients with and without burn injuries. Amikacin pharmacokinetic parameters were compared between the two groups and multiple dosing regimens were simulated using MATLAB to achieve the PD target in ≥90% of patients with burn injuries. The pharmacokinetic analysis included 282 amikacin concentrations from 70 pediatric patients with burn injuries and 99 concentrations from 32 pediatric patients without burns. A one-compartment model with first-order elimination described amikacin pharmacokinetics well for both groups. Clearance (CL) was significantly higher in patients with burn injuries than in patients without (7.22 vs 5.36 L/h, P < .001). The volume of distribution (V) was also significantly increased in patients with burn injuries (22.7 vs 18.7 L, P < .01). Weight significantly influenced amikacin CL (P < .001) and V (P < .001) for both groups. Model-based simulations showed that a higher amikacin dose (≥25 mg/kg) achieved a Cmax/MIC ≥8 in ≥90% of patients with assumed infections of organisms with an MIC = 8 mg/L. Amikacin pharmacokinetics are altered in patients with burn injuries, including a significant increase in CL and V. In simulations, increased doses (≥25 mg/kg) led to improved PD target attainment rates. Further clinical evaluation of this proposed dosing regimen is warranted to assess clinical and microbiological outcomes in pediatric patients with burn wound sepsis.

Relationship between zolpidem concentrations and sleep parameters in pediatric burn patients.

Zolpidem is a short-acting non-benzodiazepine hypnotic that is used to improve sleep architecture in patients with burn injuries. This study evaluated the relationship between zolpidem administration and sleep parameters in a cohort of children with severe burn injuries. Standard age-based zolpidem dosing practices were employed. Polysomnography data were recorded at 30-second intervals throughout the night. Serum concentrations of zolpidem were measured at 0, 1, 2, 4, 5, 6, and 8 hours after administration of the first dose. The relationship between zolpidem concentrations and sleep parameters was evaluated using Markov mixed-effects pharmacodynamic models. Ten children received two doses of zolpidem at 22:00 and 02:00 hours. The median total amount of sleep was 361.0 (interquartile range [IQR]: 299.0-418.5) minutes; approximately 65% of the normal reference value for an 8-hour period. Slow-wave and rapid eye movement (REM) sleep were also dramatically reduced (18-37% of normal). With two doses of zolpidem, stage 2 sleep was 99% of normal levels. Higher peak zolpidem concentrations were associated with increased stage 2 sleep (r = .54; P = .04). Despite this, a median of 120.0 (IQR: 99.5-143.5) transitions between nocturnal sleep stages were recorded, with a median of 55.5 (IQR: 36-75) night-time awakenings per patient. In pediatric burn patients, higher zolpidem serum concentrations were associated with restoration of stage 2 sleep to normal levels. Nonetheless, slow-wave and REM sleep were profoundly depressed with frequent transitions between sleep stages, suggesting that alternative hypnotic agents may be required to restore normal sleep architecture in severely burned children.

The effect of diphenhydramine on sleep in pediatric burn patients: a secondary analysis.

Adequate sleep is essential for maintaining homeostasis, especially when recovering from an illness; however, studies have shown that sleep disruption and sleep deprivation are common in intensive care unit patients, including children who have sustained burn injury. The purpose of this study was to evaluate the effect of diphenhydramine (DPH) on sleep in pediatric intensive care unit burn patients using Myra Levine's Conservation Model as the organizing framework. For this study, secondary analysis of polysomnography data and retrospective chart review were used. Twelve DPH patients were pair matched in terms of morphine, midazolam, and methadone with 12 non-DPH patients. The data were analyzed using paired t-tests for each dependent variable and χ analysis was used for frequency determinations. There was no difference in demographics between the two groups. DPH patients took 4.3 ± 1.6 minutes to fall asleep whereas non-DPH patients took 15.8 ± 1.6 minutes to achieve sleep onset (P = .06). Patients receiving DPH achieved 297.6 ± 29.9 minutes of total sleep time whereas those not receiving DPH achieved only 209.2 ± 29.9 minutes (P < .05). There was minimal difference in the mean percentage of sleep time in stages 3 and 4 between the two groups. The DPH group did have 50% more rapid eye movement sleep time compared with the non-DPH group. Even though DPH did not result in a statistical improvement in sleep quality, sleep quantity was increased in this study. More research is needed to find an effective sleep intervention in pediatric burn patients.

Trends in bacterial wound isolates and antimicrobial susceptibility in a pediatric burn hospital.

The purpose of this retrospective study was to collate data dealing with organisms cultured from the burn patients and evaluate trends in antimicrobial susceptibility. All cultures collected from each acute admission patient between 2004 and 2011 in the 30-bed pediatric burn hospital were evaluated for their annual frequency and antimicrobial susceptibility. Duplicate cultures were excluded. Staphylococcus aureus was isolated most frequently (25% of total isolates; range, 69-408 isolates/yr), followed by Pseudomonas aeruginosa (13%; range, 40-202 isolates/yr), coagulase-negative staphylococci (9%; range, 2-188 isolates/yr), Enterobacter cloacae (8%; range, 22-128 isolates/yr), and Escherichia coli (6%; range, 19-91 isolates/yr). This rank order remained relatively consistent during the period of study. The emergence of methicillin-resistant S. aureus increased from 20% in 2004 to about 45% in 2009 to 2011. Susceptibility to vancomycin was still 100%. In comparing periods 2004 to 2007 and 2008 to 2011, P. aeruginosa showed increased susceptibility to cefepime (from 76% to 84%) and the aminoglycosides (from 68% to 81%), whereas susceptibility to piperacillin-tazobactam remained high (from 91% to 93%). E. cloacae demonstrated 90 to 100% susceptibility to aminoglycosides, cefepime, and imipenem. E. coli showed an increased rate of resistance to ceftazidime but was still susceptible to imipenem and amikacin. S. aureus and P. aeruginosa continue to be the most prevalent organisms cultured from our pediatric burn population. Almost half of the staphylococcal isolates were methicillin-resistant S. aureus. Despite widespread use of piperacillin-tazobactam, P. aeruginosa susceptibility remained high. Several classes of antimicrobials continued to demonstrate good to excellent activity against the majority of organisms cultured from the burn patients.

Long-term posttraumatic stress symptoms vary inversely with early opiate dosing in children recovering from serious burns: effects durable at 4 years.

BACKGROUND: Children surviving serious burns are at risk for developing posttraumatic stress disorder (PTSD) as a function both of the injury and of its treatment. Short-term studies in such children have demonstrated reduced PTSD symptoms with intensive early pain control. However, the long-term impact of early pain control strategies on posttraumatic stress symptoms in children recovering from serious burn injuries has not been examined. METHODS: This was a retrospective review of a multiple time point data collection involving a cohort of 147 infants, children, and teenagers with 4 years of follow-up after serious burns conducted at 4 pediatric burn centers to examine the impact of early opiate dosing on long-term posttraumatic stress symptoms. The main outcome measure was the nine-item Short Form Child Stress Disorders Checklist, which is an established and validated assessment. The impact of total opiate dosing during the first 7 days on these scores was assessed. RESULTS: Subjects had an average age of 11 years and average injury size of 22% total body surface area burned (%TBS). The correlation between opiate units (OUs) and %TBS was 0.46 at baseline, OU increasing with increasing %TBS. OUs were strongly predictive of Child Stress Disorders Checklist scores up to 4 years, with higher OU (10 units vs. 6 and 2 units) remaining constantly different up to 4 years in predicting lower stress scores for both smaller and larger burns. CONCLUSION: Early opiate management of pain associated with acute burn wounds and burn treatment predicts the development and resolution rate of PTSD symptoms in a large multicenter sample of children hospitalized for serious burns. The effect seems to be dose related and durable at least up to 4 years in a range of burn sizes. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level II.

A performance improvement initiative to determine the impact of increasing the time interval between changing centrally placed intravascular catheters.

Existing practice guidelines designed to minimize invasive catheter infections and insertion-related complications in general intensive care unit patients are difficult to apply to the burn population. Burn-specific guidelines for optimal frequency for catheter exchange do not exist, and great variation exists among institutions. Previously, the authors' practice was to follow a new site insertion at 48 hours by an exchange over a guidewire, which was followed 48 hours later by a second guidewire exchange (48h group). As a performance improvement initiative, the authors attempted to determine whether there would be any advantage or disadvantage to extending these intervals to 72 hours (72h). All patients with centrally placed intravascular catheters from October 2007 to August 2008 were included in the 48h group, and all patients with catheters placed from September 2008 to December 2009 comprised the 72h group. Catheter infection rates were determined using the National Healthcare Safety Network definition for central line-associated bloodstream infections (CLABSIs) and calculated as CLABSIs/1000 catheter days. The two groups were not significantly different for age, sex, burn etiology, total burn size, or percent third-degree burn. There were 3.1 CLABSIs/1000 catheter days for the 48h group and 2.8 CLABSIs/1000 catheter days for the 72h group (NS). The authors conclude that increasing the central catheter change interval from 48 to 72 hours did not result in any increase in their CLABSI rate. Implementation of this change in practice is expected to decrease supply costs by $28,000 annually in addition to reducing clinical support services needed to perform these procedures.

Preliminary assessment of zolpidem pharmacokinetics in pediatric burn patients.

PURPOSE: Severely burned patients frequently experience sleep fragmentation and insomnia. This study evaluated the population pharmacokinetics of the sleep-enhancing agent zolpidem among burned children. METHODS: Zolpidem was administered according to the following age-based dosing schedule: 2.5 mg per dose for 2-4 year olds, 5.0 mg per dose for 5-10 year olds, and 10 mg per dose for older than 10 years. Serum samples were collected before and 1, 2, 4, 5, 6, and 8 hours after dosing. The population pharmacokinetic analysis modeled zolpidem concentrations using nonlinear mixed effects models. RESULTS: Eleven patients with a mean (±SD) age of 8.3 ± 4.0 years and a mean total burn surface area of 56% ± 22% were recruited. Seventy-three zolpidem concentrations were measured with a mean Cmax of 291 ± 140 ng/mL. A 2-compartment model with first-order absorption best described the data. Zolpidem clearance was estimated at 0.03 L·h(-1)·kg(-1) (relative standard error, 55%) and increased with body weight (P < 0.05). The central compartment volume of distribution was estimated at 0.05 L/kg (relative standard error, 25%), which was inversely related to the proportion of the body surface with third-degree burns (P < 0.001). CONCLUSIONS: A population pharmacokinetic model has been developed that reliably characterized the pharmacokinetic parameters of zolpidem when used as a sleep-enhancing agent among pediatric burn patients. Additional studies are needed to link this pharmacokinetic model with pharmacodynamic data, which may include an assessment of the effects of higher zolpidem doses and/or more frequent administration upon sleep architecture.

The true meshing ratio of skin graft meshers.

Skin meshing is frequently used in the coverage of extensive burn injuries as well as other skin and soft tissue wounds. This technique allows coverage of more extensive areas with smaller donor sites and prevents fluid from collecting beneath the skin grafts. The devices used to achieve this expansion differ in their technology and the use of skin carriers. In addition, many of the devices permit meshing at single or multiple ratios depending upon the device chosen. Although commonly used, there have been few definitive studies analyzing the actual expansion ratios achieved by many of these devices. The purpose of this study was to measure the actual meshing ratios achieved using some of the most commonly used skin meshers. The authors used split-thickness cadaveric skin samples provided by the regional tissue bank to compare the area of skin both before and after meshing to determine the actual expansion ratio and compared that with the ratio claimed by the device manufacturer. For all ratios greater than 1:1, the extent of actual expansion was significantly less than that expected for each device (P < .001). In addition, using devices that claimed to yield increasingly greater expansion ratios resulted in increasingly greater discrepancies between the area predicted by the device manufacturer and the actual surface area of skin (P < .01). These findings suggest that there is great variability in the expected and observed expansion ratios achieved by skin graft meshing devices. This has significant applicability to practice as it is likely to affect surgical decisions related to estimating the extent of donor area needed to cover skin and soft tissue defects.

Amish burn ointment and burdock leaf dressings: assessments of antimicrobial and cytotoxic activities.

Amish burn wound ointment (ABO) contains honey, lanolin, oils, glycerin, bees wax, and other natural additives. Although there are many anecdotal reports that this ointment covered with a burdock leaf (BL) dressing promotes burn wound healing, little scientific testing of this treatment has occurred. The goal of this study was to evaluate in vitro some of the components of this treatment modality for antimicrobial and cytotoxic activities. The ABO was tested for sterility using standard microbiological techniques. Because of the semisolid, lipid-based nature of the salve, the at-use product could not be tested in bioassays. Samples of BL and the dry ingredients (DI) used in the ointment were provided by the Amish vendor. Aqueous extracts of the DI and of the BL were prepared and freeze dried. The freeze-dried extracts were reconstituted, filtered, and tested separately on keratinocyte and fibroblast cell cultures for cytotoxicity (growth inhibition assay) and against a panel of susceptible and resistant microbes for antimicrobial activity (Nathan's agar-well diffusion assay) in a series of concentrations (% wt/vol). Neither DI nor BL extracts demonstrated antimicrobial activity against any of organisms tested. The DI extract inhibited growth of both keratinocytes and fibroblasts at the 0.1% concentration. The 0.1 and 0.03% concentrations of the BL extract were cytotoxic to both keratinocytes and fibroblasts. Although tests for microbial growth from the at-use preparation of the ABO were negative, extracts of the DI and BL did not demonstrate any antimicrobial activity. Additionally, both extracts inhibited the growth of skin cells in vitro at higher concentrations. These results suggest caution in the use of ABO and BL dressings if there is more than a minimal risk of complications from the burn injury.

Quantity and quality of nocturnal sleep affect morning glucose measurement in acutely burned children.

Hyperglycemia after severe burn injury has long been recognized, whereas sleep deprivation after burns is a more recent finding. The postburn metabolic effects of poor sleep are not clear despite reports in other populations demonstrating the association between sleep insufficiency and deleterious endocrine consequences. The aim of this study was to determine whether a relationship between sleep and glucose dynamics exists in acutely burned children. Two overnight polysomnography runs (2200 to 0600) per subject were conducted in 40 patients with a mean (± SEM) age of 9.4 ± 0.7 years, 50.1 ± 2.9% TBSA burn, and 43.2 ± 3.6% full-thickness injury. Serum glucose was drawn in the morning (0600) immediately after the sleep test. Insulin requirements during the 24-hour period preceding the 0600 glucose measurement were recorded. Generalized linear models were used by the authors to evaluate percent time in each stage of sleep, percent wake time, total sleep time, sleep efficiency, and morning serum glucose, accounting for insulin use. Increased time awake (P = .04, linear; P = .02, quadratic) and reduced time spent in stage 1 sleep (P = .03, linear) were associated with higher glucose levels. Sleep efficiency (P = .01, linear; P = .02, quadratic) and total sleep time (P = .01 linear; P = .02, quadratic) were inversely associated with glucose level. Morning glucose levels appear to be affected by the quality and quantity of overnight sleep in children who have sustained extensive burn injuries. Future research is needed to elucidate the metabolic and neuroendocrine consequences of sleep deprivation on metabolism after burns.

Burn center journal club promotes clinical research, continuing education, and evidence-based practice.

The purpose of this study was to characterize the structure, policy, implementation, and outcome measures of a burn team journal club to assess its effectiveness in promoting multidisciplinary education relative to research competency, clinical knowledge, and evidence-based practice. After 2 years of a new multidisciplinary format, an anonymous quality assurance survey was distributed to staff members of a regional pediatric burn center to evaluate the impact of the journal club on clinical and research indicators. The 24 journal club meetings evaluated in this study included a variety of topics, among which were wound healing, infection, nutrition, metabolism, sleep, medications, alternative medicine, research compliance, and child abuse. The speakers included a variety of hospital personnel: 26% researchers, 23% physicians, 20% registered nurses, and 31% other disciplines and attendance mean was 29 participants per session (range 17-50). Survey results from 30 respondents indicated that 100% judged the program to be valuable to personal educational needs and 83% indicated that format did not warrant change. According to self-report data, the journal club enhanced medical knowledge (90%), patient care (73%), research competency (70%), critical thinking (63%), and evidence-based practice (63%). Results indicate that the journal club program was well received by participants, and promoted enhanced knowledge and improved patient care. In the future, barriers to research initiatives and integration of research findings into practice warrant follow-up study. Journal club should be incorporated into the learning curriculum of burn practitioners as a means to promote critical thinking, research competency, and evidence-based clinical practice.