Nele Brusselaers

Severe burn injury in europe: a systematic review of the incidence, etiology, morbidity, and mortality

IntroductionBurn injury is a serious pathology, potentially leading to severe morbidity and significant mortality, but it also has a considerable health-economic impact. The aim of this study was to describe the European hospitalized population with severe burn injury, including the incidence, etiology, risk factors, mortality, and causes of death.MethodsThe systematic literature search (1985 to 2009) involved PubMed, the Web of Science, and the search engine Google. The reference lists and the Science Citation Index were used for hand searching (snowballing). Only studies dealing with epidemiologic issues (for example, incidence and outcome) as their major topic, on hospitalized populations with severe burn injury (in secondary and tertiary care) in Europe were included. Language restrictions were set on English, French, and Dutch.ResultsThe search led to 76 eligible studies, including more than 186,500 patients in total. The annual incidence of severe burns was 0.2 to 2.9/10,000 inhabitants with a decreasing trend in time. Almost 50% of patients were younger than 16 years, and ~60% were male patients. Flames, scalds, and contact burns were the most prevalent causes in the total population, but in children, scalds clearly dominated. Mortality was usually between 1.4% and 18% and is decreasing in time. Major risk factors for death were older age and a higher total percentage of burned surface area, as well as chronic diseases. (Multi) organ failure and sepsis were the most frequently reported causes of death. The main causes of early death (<48 hours) were burn shock and inhalation injury.ConclusionsDespite the lack of a large-scale European registration of burn injury, more epidemiologic information is available about the hospitalized population with severe burn injury than is generally presumed. National and international registration systems nevertheless remain necessary to allow better targeting of prevention campaigns and further improvement of cost-effectiveness in total burn care.

Prevention of ventilator-associated pneumonia with oral antiseptics: a systematic review and meta-analysis

BACKGROUND We did a systematic review and random effects meta-analysis of randomised trials to assess the effect of oral care with chlorhexidine or povidone-iodine on the prevalence of ventilator-associated pneumonia versus oral care without these antiseptics in adults. METHODS Studies were identified through PubMed, CINAHL, Web of Science, CENTRAL, and complementary manual searches. Eligible studies were randomised trials of mechanically ventilated adult patients receiving oral care with chlorhexidine or povidone-iodine. Relative risks (RR) and 95% CIs were calculated with the Mantel-Haenszel model and heterogeneity was assessed with the I(2) test. FINDINGS 14 studies were included (2481 patients), 12 investigating the effect of chlorhexidine (2341 patients) and two of povidone-iodine (140 patients). Overall, antiseptic use resulted in a significant risk reduction of ventilator-associated pneumonia (RR 0.67; 95% CI 0.50-0.88; p=0.004). Chlorhexidine application was shown to be effective (RR 0.72; 95% CI 0.55-0.94; p=0.02), whereas the effect resulting from povidone-iodine remains unclear (RR 0.39; 95% CI 0.11-1.36; p=0.14). Heterogeneity was moderate (I(2)=29%; p=0.16) for the trials using chlorhexidine and high (I(2)=67%; p=0.08) for those assessing povidone-iodine use. Favourable effects were more pronounced in subgroup analyses for 2% chlorhexidine (RR 0.53, 95% CI 0.31-0.91), and in cardiosurgical studies (RR 0.41, 95% CI 0.17-0.98). INTERPRETATION This analysis showed a beneficial effect of oral antiseptic use in prevention of ventilator-associated pneumonia. Clinicians should take these findings into account when providing oral care to intubated patients. FUNDING None.

The rising problem of antimicrobial resistance in the intensive care unit

Mainly due to its extremely vulnerable population of critically ill patients, and the high use of (invasive) procedures, the intensive care unit (ICU) is the epicenter of infections. These infections are associated with an important rise in morbidity, mortality, and healthcare costs. The additional problem of multidrug-resistant pathogens boosts the adverse impact of infections in ICUs. Several factors influence the rapid spread of multidrug-resistant pathogens in the ICU, e.g., new mutations, selection of resistant strains, and suboptimal infection control. Among gram-positive organisms, the most important resistant microorganisms in the ICU are currently methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. In gram-negative bacteria, the resistance is mainly due to the rapid increase of extended-spectrum Beta-lactamases (ESBLs) in Klebsiella pneumonia, Escherichia coli, and Proteus species and high level third-generation cephalosporin Beta-lactamase resistance among Enterobacter spp. and Citrobacter spp., and multidrug resistance in Pseudomonas aeruginosa and Acinetobacter species. To conclude, additional efforts are needed in the future to slow down the emergence of antimicrobial resistance. Constant evaluation of current practice on basis of trends in MDR and antibiotic consumption patterns is essential to make progress in this problematic matter.

A clinical algorithm to diagnose invasive pulmonary aspergillosis in critically ill patients.

RATIONALE The clinical relevance of Aspergillus-positive endotracheal aspirates in critically ill patients is difficult to assess. OBJECTIVES We externally validate a clinical algorithm to discriminate Aspergillus colonization from putative invasive pulmonary aspergillosis in this patient group. METHODS We performed a multicenter (n = 30) observational study including critically ill patients with one or more Aspergillus-positive endotracheal aspirate cultures (n = 524). The diagnostic accuracy of this algorithm was evaluated using 115 patients with histopathologic data, considered the gold standard. Subsequently, the diagnostic workout of the algorithm was compared on the total cohort (n = 524), with the categorization based on the diagnostic criteria of the European Organization for the Research and Treatment of Cancer/Mycoses Study Group. MEASUREMENTS AND MAIN RESULTS Among 115 histopathology-controlled patients, 79 had proven aspergillosis. The algorithm judged 86 of 115 cases to have putative aspergillosis. This diagnosis was confirmed in 72 and rejected in 14 patients. The algorithm judged 29 patients to have Aspergillus colonization. This was confirmed in 22 and rejected in 7 patients. The algorithm had a specificity of 61% and a sensitivity of 92%. The positive and negative predictive values were 61 and 92%, respectively. In the total cohort (n = 524), 79 patients had proven invasive pulmonary aspergillosis (15.1%). According to the European Organization for the Research and Treatment of Cancer/Mycoses Study Group criteria, 32 patients had probable aspergillosis (6.1%) and 413 patients were not classifiable (78.8%). The algorithm judged 199 patients to have putative aspergillosis (38.0%) and 246 to have Aspergillus colonization (46.9%). CONCLUSIONS The algorithm demonstrated favorable operating characteristics to discriminate Aspergillus respiratory tract colonization from invasive pulmonary aspergillosis in critically ill patients.

Development and validation of a model for prediction of mortality in patients with acute burn injury

The objective was to develop a user‐friendly model to predict the probability of death from acute burns soon after injury, based on burned surface area, age and presence of inhalation injury.

Outcome of acute kidney injury in severe burns: a systematic review and meta-analysis

PurposeThe main objective of this review was to analyse the prevalence and outcome of acute kidney injury (AKI) in patients with severe burn injury. AKI is a common complication in patients with severe burn injury and one of the major causes of death (often combined with other organ dysfunctions). Several definitions of AKI have been used, but the RIFLE ‘consensus’ classification is nowadays considered the gold standard, enabling a more objective comparison of populations.MethodsWe performed a systematic literature search (1960–2009), involving PubMed, the Web of Science, the search engine Google™ and textbooks. Reference lists and the Science Citation Index search were also consulted. Attributable mortality was assessed by performing a meta-analysis.ResultsThis search yielded 57 articles and abstracts with relevant epidemiologic data of AKI in the burn population. Of these, 30 contained complete mortality data of the burn and control population, which revealed a 3- to 6-fold higher mortality for AKI patients in univariate analysis, depending on the applied definition. When defined by the RIFLE consensus classification, AKI occurred in one quarter of patients with severe burn injury (median mortality of 34.9%), and when defined by the need for renal replacement therapy (RRT), AKI occurred in 3% (median mortality of 80%). The prevalence of AKI slightly increased, but AKI-RRT decreased. However, the outcome in both groups improved.ConclusionDespite the wide variation of the analysed burn populations and definitions of AKI, this review clearly showed that AKI remains prevalent and is associated with increased mortality in patients with severe burn injury.

Hospital and surgeon volume in relation to long-term survival after oesophagectomy: systematic review and meta-analysis

Background Centralisation of healthcare, especially for advanced cancer surgery, has been a matter of debate. Clear short-term mortality benefits have been described for oesophageal cancer surgery conducted at high-volume hospitals and by high-volume surgeons. Objective To clarify the association between hospital volume, surgeon volume and hospital type in relation to long-term survival after oesophagectomy for cancer, by a meta-analysis. Design The systematic literature search included PubMed, Web of Science, Cochrane library, EMBASE and Science Citation Index, for the period 1990–2013. Eligible articles were those which reported survival (time to death) as HRs after oesophagectomy for cancer by hospital volume, surgeon volume or hospital type. Fully adjusted HRs for the longest follow-up were the main outcomes. Results were pooled by a meta-analysis, and reported as HRs and 95% CIs. Results Sixteen studies from seven countries met the inclusion criteria. These studies reported hospital volume (N=13), surgeon volume (N=4) or hospital type (N=4). A survival benefit was found for high-volume hospitals (HR=0.82, 95% CI 0.75 to 0.90), and possibly also, for high-volume surgeons (HR=0.87, 95% CI 0.74 to 1.02) compared with their low-volume counterparts. No association with survival remained for hospital volume after adjustment for surgeon volume (HR=1.01, 95% CI 0.97 to 1.06; N=2), while a survival benefit was found in favour of high-volume surgeons after adjustment for hospital volume (HR=0.91, 95% CI 0.85 to 0.98; N=2). Conclusions This meta-analysis demonstrated better long-term survival (even after excluding early deaths) after oesophagectomy with high-volume surgery, and surgeon volume might be more important than hospital volume. These findings support centralisation with fewer surgeons working at large centres.

Burn scar assessment: A systematic review of objective scar assessment tools

PURPOSE All deep second and third degree burns are at risk to develop hypertrophic scars which can severely undermine the quality of survival. To assess the severity of scarring, several technical devices or tools have been introduced to evaluate one or more aspects of the scar, enabling comparison of different treatment protocols and allowing an objective follow-up. The objective of this study was to review which tools can be used in objective burn scar assessment. BASIC PROCEDURES The Systematic literature search involving PubMed, the Web of Science (incl. Science Citation Index). MAIN FINDINGS 51 articles with burn scar assessment as main topic were found. Several characteristics of the scar can be assessed, such as color, metric features and elasticity, but none of the available tools covers the whole aspect of the scar. Especially subjective factors such as pain and itching cannot be assessed with those tools, in spite of their great impact on the patients quality of life. CONCLUSIONS Scar tools enable objective and reproducible evaluation of scars, which is essential for scientific studies and medico-legal purposes, and in selected cases for the clinical follow-up of an individual patient. Further studies to evaluate these tools on scars are nevertheless required.

Clinical Use of HIV Integrase Inhibitors: A Systematic Review and Meta-Analysis

Background Optimal regimen choice of antiretroviral therapy is essential to achieve long-term clinical success. Integrase inhibitors have swiftly been adopted as part of current antiretroviral regimens. The purpose of this study was to review the evidence for integrase inhibitor use in clinical settings. Methods MEDLINE and Web-of-Science were screened from April 2006 until November 2012, as were hand-searched scientific meeting proceedings. Multiple reviewers independently screened 1323 citations in duplicate to identify randomized controlled trials, nonrandomized controlled trials and cohort studies on integrase inhibitor use in clinical practice. Independent, duplicate data extraction and quality assessment were conducted. Results 48 unique studies were included on the use of integrase inhibitors in antiretroviral therapy-naive patients and treatment-experienced patients with either virological failure or switching to integrase inhibitors while virologically suppressed. On the selected studies with comparable outcome measures and indication (n = 16), a meta-analysis was performed based on modified intention-to-treat (mITT), on-treatment (OT) and as-treated (AT) virological outcome data. In therapy-naive patients, favorable odds ratios (OR) for integrase inhibitor-based regimens were observed, (mITT OR 0.71, 95% CI 0.59–0.86). However, integrase inhibitors combined with protease inhibitors only did not result in a significant better virological outcome. Evidence further supported integrase inhibitor use following virological failure (mITT OR 0.27; 95% CI 0.11–0.66), but switching to integrase inhibitors from a high genetic barrier drug during successful treatment was not supported (mITT OR 1.43; 95% CI 0.89–2.31). Integrase inhibitor-based regimens result in similar immunological responses compared to other regimens. A low genetic barrier to drug-resistance development was observed for raltegravir and elvitegravir, but not for dolutegravir. Conclusion In first-line therapy, integrase inhibitors are superior to other regimens. Integrase inhibitor use after virological failure is supported as well by the meta-analysis. Careful use is however warranted when replacing a high genetic barrier drug in treatment-experienced patients switching successful treatment.

Skin replacement in burn wounds.

Historically, the main goal in burn management was increasing the survival of severely burned patients by rapid debridement and early closure of burn wounds, consequently reducing the infection risk.1–4 However, in the last decennia, surgical emphasis has shifted from survival to “quality of survival,” especially by improving the residual scars and preventing contractures. Traditionally, surgeons divide burns into deep burns requiring surgical therapy, and superficial burns which heal spontaneous by re-epithelialization with minimal scarring. Nevertheless, there is a gray zone between those two groups in which therapeutic decision making is difficult. The final decision for surgery generally remains case and surgeon dependent, and will mainly depend on the total burned surface area.5 Wound closure can be obtained by diverse therapeutic modalities depending on the depth and healing potential of the burn wound.5 In this article, the main focus is on the surgical treatment of deep dermal and full thickness burns. We endeavor to give a comprehensive overview of the developments in skin substitutes, which is impossible without mentioning some alternative treatments. The current golden standard for deep burns is surgical debridement and closure with autologous split thickness skin grafts or “STG” (epidermis plus a thin layer of dermis). Nevertheless, donor areas are limited in extended burns, and the residual scars remain unsatisfactory due to the lack of dermis. A more aesthetical reconstruction can be obtained with full thickness skin grafts (epidermis and whole dermis), which are limited in dimension and can only be harvested in a few areas (groin, lower abdomen, etc.). Deep defects with exposed bone or neurovascular structures are currently treated with flap surgery, which gives an optimal aesthetical and functional result. Nevertheless, the severe donor-site morbidity, the technical difficulty, and sometimes severe complications limit its use mostly to secondary reconstructions. Consequently, alternative conservative and surgical treatments were developed to improve the healing and the quality of the residual scars.6 Several mechanisms are supposed to enhance healing: (i) providing the ideal wound environment (wound dressings, etc.), (ii) by assisting the intrinsic healing capacities (growth factors, cytokines, etc.), or (iii) by surgically replacing the damaged skin (“skin substitutes”), which also should reduce scarring in full thickness defects. A permanent skin substitute is a surgically fixated “long lasting” skin replacement, consisting of naturally occurring skin elements which become incorporated in the normal skin. The main issue of this definition is the longevity of a skin substitute, which seems to be mostly of commercial importance, where terms such as biological dressings, and permanent and temporary skin substitutes are used without a clear distinction. This literature review showed that technically similar products are commercialized as “permanent” by one company and as biological dressing by another. Therefore, we chose to divide all these products in the following categories, depending on the skin layer which is (temporary) replaced: epidermal, dermal and combined skin substitutes (or composite grafts; Fig. 1). In the future, a fourth group might need to be added: the combined skin substitute with a subcutaneous adipose layer.7 However, the difference between skin replacements and some wound dressings can be small. Wound dressings are intended for coverage instead of replacement, to optimize wound healing. Wound dressings can roughly be divided in dressings containing natural elements (such as honey ointments), synthetic dressings (such as silver-impregnated dressings), and biological dressings containing mammalian cells or cell-derived substances like collagens and growth factors (human donor skin). Synthetically manufactured, naturally occurring elements, such as cellulose membranes, are also synthetic dressings. Wound dressings are not considered as (permanent) skin substitutes because they are not incorporated in the healing wound. Some authors previously named some of these products “skin substitutes” (without mentioning “permanent”) but this only lead to confusing terminology. The most important biological dressing, used since the 1940s, is human donor skin or “cadaver skin.”8 It contains several beneficial factors (growth factors, cytokines, etc.), and it provides the ideal environment for healing. Because of better preservation techniques (glycerol or cryopreserved), the risk of infection transmission is minimized, and its rejection will be delayed up to 3 weeks to 5 weeks.8,9 One of the Submitted for publication May 18, 2009. Accepted for publication November 6, 2009. Copyright