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

Introduction: Fibrin sealants (FS) have been approved for use in the United States since 1998. Since approval, they have been used in a wide variety of clinical settings and new products continue to be introduced. Areas covered: This review covers the literature supporting the USA FDA-approved indications for FS products produced by Baxter Corp. Literature review of PubMed, the Cochrane Library, FDA approval documents and product websites yielded information contained in this article. Mechanism of action, efficacy and safety of these products are covered. Expert opinion: FS are generally safe, popular and are used for a wide variety of off-label indications. Their use appears to be expanding rapidly. For many uses, including approved ones, large well-controlled trials are still needed. Additionally, cost-effectiveness data for these products would be a great benefit in guiding their future use.

Fibrin sealants: surgical hemostat, sealant and adhesive.

The neuropeptide substance P (SP) is a known inflammatory mediator released from cutaneous peripheral nerve terminals. SP effects on cellular composition in the cutaneous response to injury remain unclear. Based on our previous observations about SP effects on wound repair, we hypothesized that topical SP increases inflammatory cell density infiltration early after injury. A full-thickness 1.5 x 1.5 cm(2) wound was created on the dorsum of 8-9-week-old C57BL/6J-m+Lepr(db) mice (db/db). Wounds were treated daily with 300 muL of either normal saline (0.9% NaCl) or 10(-9) M SP for 7 days. Three wounds from each group were harvested at 2, 3, 7, 14, and 28 days. Samples underwent enzymatic digestion and were incubated with fluorescent-labeled antibodies. Using flow cytometry, cellular content and density for each sample was derived. Masson Trichrome stained histology specimens were prepared to confirm results. Cell density in the SP-treated wounds (11.3 x 10(7) cells/g tissue, standard deviation [SD]+/-1.5 x 10(7)) was greater than in NaCl-treated wounds (7 x 10(7) cells/g tissue, SD+/-2.3 x 10(7), p<0.05) at day 7 postwounding. SP significantly increased the density of leukocytes (2.1 x 10(7), SD +/-3.6 x 10(6) vs. 1.8 x 10(7), SD+/-4.9 x 10(5), p<0.02) 3 days after wounding and the density of macrophages (2.9 x 10(7), SD+/-7.5 x 10(6) vs. 1.3 x 10(7), SD+/-1.4 x 10(6), p<0.05) 7 days after wounding. There were no significant differences in endothelial cell, leukocyte, or macrophage density at later time points. Topical SP treatment increases early inflammatory density in the healing wounds of db/db mice. These data support a role for nerve-mediated inflammation in cutaneous wound repair.

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Topical substance P increases inflammatory cell density in genetically diabetic murine wounds.

Early aggressive fluid resuscitation has significantly decreased the morbidity and mortality associated with volume losses from large burns. Although most patients are adequately resuscitated using the Parkland formula, we noted increased fluid requirements for shock resuscitation in patients involved in methamphetamine laboratory explosions. Because predominant users are young healthy individuals in their 20s and 30s, we had not anticipated burn shock resuscitation failures in this patient group. We reviewed our experience with burn patients with documented methamphetamine use to determine whether this patient group presents new dilemmas to the burn surgeon. A 2-year retrospective study of 30 patients (15 methamphetamine users, 15 controls) revealed that the methamphetamine burn patient requires two to three times the standard Parkland formula resuscitation. In this study, methamphetamine burns larger than 40% TBSA had a 100% mortality.

The methamphetamine burn patient.

BACKGROUND: With unprecedented survival rates in modern burn care, there is increasing focus on optimizing long-term functional outcomes. However, 3% to 8% of patients admitted to burn centers still die of injury. Patterns in which these patients progress to death remain poorly characterized. We hypothesized that burn nonsurvivors will follow distinct temporal distributions and patterns of decline, parallel to the trimodality of deaths previously described for trauma. METHODS: We retrospectively identified all adult deaths from 1995 to 2007 in the National Burn Repository database (n = 5,975) and at our regional burn center (n = 237). We stratified patients by age and analyzed injury and death characteristics. We used objective criteria to allocate nonsurvivors to one of four trajectories: early rapid decline, early organ failure, late sudden death, or late-onset decline. RESULTS: The greatest concentration of deaths in both samples and age groups occurred within 72 hours of injury and decreased subsequently with no later mortality peak. Death was most often caused by burn shock within the first week of injury, cardiogenic shock or lung injury in Weeks 1 to 2, and sepsis/multiorgan failure after Week 2. In decreasing frequency, trajectories to death fit the pattern of early rapid decline (58%), early organ failure (20%), late-onset decline (16%), and late sudden death (6%). CONCLUSION: Most burn deaths follow a pattern of early rapid decline or early organ failure manifested by death or critical illness within several days of the burn. These findings indicate that more than three quarters of burn deaths are attributable to failure or significant decompensation beginning in the resuscitation phase. Sporadic deaths later in hospitalization are uncommon. Despite significant advances in burn resuscitation, our data indicate that ongoing efforts to mitigate deaths in modern burn care should still focus on care improvements in the resuscitation phase. LEVEL OF EVIDENCE: Epidemiologic study, level III. Language: en

Trajectories to death in patients with burn injury.

The rising number of obese patients poses new challenges for burn care. These may include adjustments in calculations of burn size, resuscitation, ventilator wean, nutritional goals as well as challenges in mobilization. The authors have focused this observational study on resuscitation in the obese patient population in the first 48 hours after burn injury. Previous trauma studies suggest a prolonged time to reach end points of resuscitation in the obese compared to nonobese injured patients. The authors hypothesize that obese patients have worse outcomes after thermal injury and that differences in the response to resuscitation contribute to this disparity. The authors retrospectively analyzed data prospectively collected in a multicenter trial to compare resuscitation and outcomes in patients stratified by National Institutes of Health/World Health Organization body mass index (BMI) classification (BMI: normal weight, 18.5-24.9; overweight, 25-29.9, obese, 30-39.9; morbidly obese, ≥40). Because of the distribution of body habitus in the obese, total burn size was recalculated for all patients by using the method proposed by Neaman and compared with Lund-Browder estimates. The authors analyzed patients by BMI class for fluids administered and end points of resuscitation at 24 and 48 hours. Multivariate analysis was used to compare morbidity and mortality across BMI groups. The authors identified 296 adult patients with a mean TBSA of 41%. Patient and injury characteristics were similar across BMI categories. No significant differences were observed in burn size calculations by using Neaman vs Lund-Browder formulas. Although resuscitation volumes exceeded the predicted formula in all BMI categories, higher BMI was associated with less fluid administered per actual body weight (P = .001). Base deficit on admission was highest in the morbidly obese group at 24 and 48 hours. Furthermore, the morbidly obese patients did not correct their metabolic acidosis to the extent of their lower BMI counterparts (P values .04 and .03). Complications and morbidities across BMI groups were similar, although examination of organ failure scores indicated more severe organ dysfunction in the morbidly obese group. Compared with being normal weight, being morbidly obese was an independent risk factor for death (odds ratio = 10.1; confidence interval, 1.94-52.5; P = .006). Morbidly obese patients with severe burns tend to receive closer to predicted fluid resuscitation volumes for their actual weight. However, this patient group has persistent metabolic acidosis during the resuscitation phase and is at risk of developing more severe multiple organ failure. These factors may contribute to higher mortality risk in the morbidly obese burn patient.

Nicole S. Gibran

Papers

Fibrin sealants: surgical hemostat, sealant and adhesive.

Topical substance P increases inflammatory cell density in genetically diabetic murine wounds.

The methamphetamine burn patient.

Trajectories to death in patients with burn injury.

Differences in resuscitation in morbidly obese burn patients may contribute to high mortality.