The R package mice imputes incomplete multivariate data by chained equations. The software mice 1.0 appeared in the year 2000 as an S-PLUS library, and in 2001 as an R package. mice 1.0 introduced predictor selection, passive imputation and automatic pooling. This article documents mice, which extends the functionality of mice 1.0 in several ways. In mice, the analysis of imputed data is made completely general, whereas the range of models under which pooling works is substantially extended. mice adds new functionality for imputing multilevel data, automatic predictor selection, data handling, post-processing imputed values, specialized pooling routines, model selection tools, and diagnostic graphs. Imputation of categorical data is improved in order to bypass problems caused by perfect prediction. Special attention is paid to transformations, sum scores, indices and interactions using passive imputation, and to the proper setup of the predictor matrix. mice can be downloaded from the Comprehensive R Archive Network. This article provides a hands-on, stepwise approach to solve applied incomplete data problems.

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mice: Multivariate Imputation by Chained Equations in R

Secret History: Return of the Black Death Channel 4, 7-8pm In 1348 the Black Death swept through London, killing people within days of the appearance of their first symptoms. Exactly how many died, and why, has long been a mystery. This Secret History documentary follows experts as they pick through the evidence and reveal why the plague killed on such a scale. And they ask, what might be coming next?

Medscape

Werner, Sabine, and Richard Grose. Regulation of Wound Healing by Growth Factors and Cytokines. Physiol Rev 83: 835–870, 2003; 10.1152/physrev.00032.2002.—Cutaneous wound healing is a complex proce...

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Regulation of Wound Healing by Growth Factors and Cytokines

This document represents the first collaboration between 2 organizations-the American Society for Parenteral and Enteral Nutrition and the Society of Critical Care Medicine-to describe best practices in nutrition therapy in critically ill children. The target of these guidelines is intended to be the pediatric critically ill patient (>1 month and 2-3 days in a PICU admitting medical, surgical, and cardiac patients. In total, 2032 citations were scanned for relevance. The PubMed/MEDLINE search resulted in 960 citations for clinical trials and 925 citations for cohort studies. The EMBASE search for clinical trials culled 1661 citations. In total, the search for clinical trials yielded 1107 citations, whereas the cohort search yielded 925. After careful review, 16 randomized controlled trials and 37 cohort studies appeared to answer 1 of the 8 preidentified question groups for this guideline. We used the GRADE criteria (Grading of Recommendations, Assessment, Development, and Evaluation) to adjust the evidence grade based on assessment of the quality of study design and execution. These guidelines are not intended for neonates or adult patients. The guidelines reiterate the importance of nutrition assessment-particularly, the detection of malnourished patients who are most vulnerable and therefore may benefit from timely intervention. There is a need for renewed focus on accurate estimation of energy needs and attention to optimizing protein intake. Indirect calorimetry, where feasible, and cautious use of estimating equations and increased surveillance for unintended caloric underfeeding and overfeeding are recommended. Optimal protein intake and its correlation with clinical outcomes are areas of great interest. The optimal route and timing of nutrient delivery are areas of intense debate and investigations. Enteral nutrition remains the preferred route for nutrient delivery. Several strategies to optimize enteral nutrition during critical illness have emerged. The role of supplemental parenteral nutrition has been highlighted, and a delayed approach appears to be beneficial. Immunonutrition cannot be currently recommended. Overall, the pediatric critical care population is heterogeneous, and a nuanced approach to individualizing nutrition support with the aim of improving clinical outcomes is necessary.

Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.)

Morbidity and mortality from sepsis remains unacceptably high. Large variability in clinical practice, plus the increasing awareness that certain processes of care associated with improved critical...

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Severe sepsis and septic shock

We have previously shown that the expression of collagenase mRNA and activity are suppressed in fibroblasts derived from postburn hypertrophic scar. Although it is known that differential synthesis of collagen and collagenase in postburn hypertrophic scar is one of the main reasons for the excessive accumulation of collagen, it is not clear why the expression of collagenase in hypertrophic scar fibroblasts is suppressed relative to that in normal fibroblasts. In this study, we hypothesized that dermal fibroblasts from deeper layers of skin, which normally migrate toward the wound site, have a different capacity to express key extracellular matrix proteins such as collagenase and types I and III procollagen. To test this hypothesis, we established four different pairs of hypertrophic and site-matched normal cell strains from four different patients with postburn hypertrophic scarring. In another set of experiments, ten different cell strains from two normal human skin samples that were horizontally sectioned into five different layers (layers 1-5 correspond to upper to deeper layers, respectively) were established in culture. Cells at the same passages were harvested, total RNA was extracted, and Northern analysis was conducted to determine the level of collagenase and types I and III procollagen mRNA expression in each cell strain. The results of Northern blot analysis showed two transcripts each for the pro alpha1(I) collagen chain (5.8 and 4.8 kb) and for the pro alpha1(III) collagen chain (5.4 and 4.8 kb) in all cell strains examined. The intensity of the pro alpha1(I) chain of type I procollagen mRNA varied, ranging from 50.8 to 137.1 and 44.4 to 131.5 densitometry units among either normal or hypertrophic scar cells examined, respectively. Similarly, the relative quantity of type III procollagen transcript also varied, ranging from 10.4 to 91.1 and 28.7 to 116.1 among normal and hypertrophic scar cells, respectively. When five different skin layers from each tissue sample were evaluated for functional cell heterogeneity, the results showed a marked variation in expression of mRNA for type I and III procollagen. Although the level of collagenase mRNA also varied among different cell strains examined, the expression of collagenase mRNA was lower in fibroblasts derived from deeper layers of each skin sample. In conclusion, cells from different layers of normal skin samples are heterogeneous in their constitutive expression of some key extracellular matrix components such as collagenase and types I and III procollagen.

Nerve growth factor accelerates wound healing in diabetic mice

Goulian and Watson knives work well for tangential burn excision on large flat areas. They do not work well in small areas and in areas with a three-dimensional structure. The Versa-jet Hydrosurgery System (Smith and Nephew, Key Largo, FL) is a new wateriet-powered surgical tool designed for wound excision. The small size of the cutting nozzle and the ability to easily maneuver the water dissector into small spaces makes it a potentially useful tool for excision of burns of the eyelids, digits and web spaces. The Versajet Hydrosurgery System contains a power console that propels saline through a handheld cutting device. This stream of pressurized saline functions as a knife. We have used the Versajet for burn excision in 44 patients. Although there is a learning curve for both surgeons using and operating room staff setting up the device, the Versajet provides a relatively facile method for excision of challenging aesthetic and functional areas.

The Versajet water dissector: a new tool for tangential excision.

Histology of the thick scar on the female, red Duroc pig: final similarities to human hypertrophic scar.

Despite advances in medical and surgical techniques, older adults tend to be at high risk for adverse outcomes following burn injury. The purpose of this study was to examine the relative impacts of age and medical comorbidities on outcome following injury in a cohort of older adults. This was a retrospective study of all patients age 55 and over admitted to the University of Washington Burn Center from 1999 to 2003. To examine the effect of baseline medical comorbidities on outcome, a Charlson Comorbidity Index score was calculated for each patient. Multivariate regression analyses were used to examine the impact of age and comorbidities on mortality and other complications. Patient records were also matched with the National Death Index to determine the effects of age and comorbidities on mortality within 1 year following hospital discharge. A total of 325 patients who were of 55 years and older were admitted to the burn center during the 5-year study period. The overall mortality rate was 18.5%. Mortality was independently associated with age, inhalation injury, and burn size. One-year mortality was significantly associated with those older than age 75 and the Charlson score. Longer length of stay was significantly associated with burn size, inhalation injury, and total number of in-hospital complications. This study demonstrates that patient age-independent of baseline medical comorbidities-and TBSA burn are the most significant factors impacting in-hospital mortality risk following burn injury. Higher number of medical comorbidities was associated with increased mortality risk within 1 year following discharge.

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Influence of comorbidities and age on outcome following burn injury in older adults.

Hypertrophic scarring after burns is an unsolved problem and remains as devastating today as it was in the 40s and it may be that the main reason for this is the lack of an accepted, useful animal model. The female, red Duroc pig was described as a model of hypertrophic scarring nearly 30 years ago but then vanished from the literature. This seemed strange since the authors reported that 12 of 12 pigs developed thick scar. In the mid 90s we explored the model and found that, indeed, the red Duroc pig does make thick scar. Other authors have established that the Yorkshire pig does not heal in this fashion so there is the possibility of a same species control. We have continued to explore the Duroc/Yorkshire model and herein describe our experiences. Is it a perfect model of hypertrophic scarring? No. Is it a useful model of hypertrophic scarring? Time will tell. We have now obtained gene expression data from the Duroc/Yorkshire model and analysis is underway.

Nicole S. Gibran

Papers

Nerve growth factor accelerates wound healing in diabetic mice

The Versajet water dissector: a new tool for tangential excision.

Histology of the thick scar on the female, red Duroc pig: final similarities to human hypertrophic scar.

Influence of comorbidities and age on outcome following burn injury in older adults.

Review of the female Duroc/Yorkshire pig model of human fibroproliferative scarring.