Diabetes and necrotizing soft tissue infections-A prospective observational cohort study: Statistical analysis plan.

BACKGROUND: Necrotizing soft tissue infections (NSTIs) are rare but carry a high morbidity and mortality. The multicenter INFECT project aims to improve the understanding of the pathogenesis, clinical characteristics, diagnosis, and prognosis of NSTIs. This article describes the study outline and statistical analyses that will be used. METHODS: Within the framework of INFECT project, patients with NSTI at 5 Scandinavian hospitals are enrolled in a prospective observational cohort study. The goal is to evaluate outcome and characteristics for patients with NSTI and diabetes compared to patients with NSTI without diabetes. The primary outcome is mortality at 90 days after inclusion. Secondary outcomes include days alive and out of ICU and hospital, SAPS II, SOFA score, infectious etiology, amputation, affected body area, and renal replacement therapy. Comparison in mortality between patients with diabetes type 1 and 2 as well as between insulin-treated and non-insulin-treated diabetes patients will be made. Clinical data for diabetic patients with NSTI will be reported. CONCLUSION: The study will provide important data on patients with NSTI and diabetes.

Necrotizing soft tissue infections - a multicentre, prospective observational study (INFECT): protocol and statistical analysis plan.

BACKGROUND: The INFECT project aims to advance our understanding of the pathophysiological mechanisms in necrotizing soft tissue infections (NSTIs). The INFECT observational study is part of the INFECT project with the aim of studying the clinical profile of patients with NSTIs and correlating these to patient-important outcomes. With this protocol and statistical analysis plan we describe the methods used to obtain data and the details of the planned analyses. METHODS: The INFECT study is a multicentre, prospective observational cohort study. Patients with NSTIs are enrolled in five Scandinavian hospitals, which are all referral centres for NSTIs. The primary outcomes are the descriptive variables of the patients. Secondary outcomes include identification of factors associated with 90-day mortality and amputation; associations between affected body part, maximum skin defect and Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score and 90-day mortality; 90-day mortality in patients with and without acute kidney injury (AKI) and LRINEC score of six and above or below six; and association between affected body part at arrival and microbiological findings. Exploratory outcomes include univariate analyses of baseline characteristics associations with 90-day mortality. The statistical analyses will be conducted in accordance with the predefined statistical analysis plan. CONCLUSION: Necrotizing soft tissue infections result in severe morbidity and mortality. The INFECT study will be the largest prospective study in patients with NSTIs to date and will provide important data for clinicians, researchers and policy makers on the characteristics and outcomes of these patients.

A series of severe necrotising soft-tissue infections in a regional centre in Sweden.

BACKGROUND: Necrotising soft-tissue infections (NSTIs) are rare conditions with high morbidity and mortality. Patients with NSTIs are often transferred to tertiary hospitals, but the question of whether the potential benefits of highly specialised care outweigh the risks associated with inter-hospital transfers has been raised. METHODS: Prospective study including all patients with NSTIs treated at the intensive care unit at Sahlgrenska University Hospital/East between January 2008 and December 2011. RESULTS: Twenty-nine patients with NSTIs were identified. Their median age was 54 years and 69% were men. Major co-morbidities were present in 45%. Seventeen patients (59%) were referred from other hospitals. Only 33% of the patients were correctly diagnosed or suspected of having NSTIs in the emergency department. Group A Streptococcus was the most common microbiological finding (41%), followed by Enterobacteriaceae (17%). The median time from hospitalisation to the first dose of antibiotics was 6 h and the median time to primary surgery was 16 h. Hyperbaric oxygen therapy was given to 86%, and intravenous immunoglobulin was given in 52% of the cases. The 30-day mortality was 14% (4/29). The times to the first dose of antibiotics, intensive care unit admission and primary surgery did not differ between transferred and directly admitted patients, and there was no difference in outcome between the groups. CONCLUSIONS: Patients with NSTIs develop severe local and systemic symptoms and require extremely resource-demanding hospitalisation. Inter-hospital transfer was not associated with a delay in key interventions and could not be identified as a risk factor for adverse outcome.

Effects of hyperbaric oxygen on expression of fibrinolytic factors of human endothelium in a simulated ischaemia/reperfusion situation.

BACKGROUND: Treatment with hyperbaric oxygen (HBO2) is controversial when treating disorders other than decompression sickness. Still, HBO2 is a treatment modality that has gained recognition in certain situations of ischaemia reperfusion. However, not much is known about its effect on the endothelial cells. Based on earlier studies, the hypothesis was that HBO2 treatment stimulates the release of fibrinolytic factors. The aim of the study was to investigate the effect of HBO2 treatment on cultured endothelial cells in a simulated ischaemia-reperfusion model. METHODS: To mimic the clinical situation during ischaemia reperfusion, endothelial cells were subjected to anoxia for 8 h, followed by reperfusion with either HBO2 or normobaric air for 1.5 h, and compared with an untreated control that was not exposed to anoxia. Components investigated were the fibrinolytic stimulator tissue plasminogen activator (t-PA), urokinase plasminogen activator (uPA) and the antagonist. plasminogen activator inhibitor type one (PAI-1). RESULTS: Immediately after 8 h of total anoxia and reoxygenation with HBO2 (for 1.5 h), the mean (SEM) concentrations of t-PA, PAI-1 and uPA were significantly increased compared to the other groups. The difference between the normobaric and control groups, measured at 1.5 h, 6 h and 24 h post-anoxia, persisted throughout the experiment. CONCLUSION: In this ischaemia-reperfusion model. HBO2 stimulates the release of fibrinolytic factors. These observations might be relevant in trauma care in preventing thromboses and/or microembolization following ischaemia-reperfusion.

Treatment with hyperbaric oxygen affects endothelial cell fibrinolysis.

OBJECTIVE: To investigate the effect of hyperbaric oxygen treatment (HBO) on the thrombolytic properties of endothelial cells. SETTING: University hospital, Sweden. INTERVENTIONS: Human endothelial cells were derived from saphenous veins, and exposed to oxygen in a compression chamber at 2.5 atmospheres absolute (ATA, =250kPa). Cells exposed to 2.5 ATA with a gas mixture similar to air (HB Air), and unpressurised air-exposed cells served as controls. MAIN OUTCOME MEASURES: Tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1). RESULTS: Immediately after treatment there was a significant increase in t-PA protein in the medium in cultures treated with HBO compared with HB Air (p = 0.015, n = 6), and untreated controls (p = 0.015, n = 6). The PAI-1 concentration in media was also higher in the HBO-treated group compared with HB Air (p = 0.004, n = 6) and untreated controls (p = 0.004, n = 6). Six hours after treatment there was still a significant increase in PAI-1 in the HBO-treated group compared with untreated controls (p = 0.007, n = 6), but not with the pressure control. t-PA concentrations were similar. Specific mRNA for t-PA and PAI-1 was detectable immediately after treatment and six hours later in all experimental groups as assessed by reverse transcriptase polymerase chain reaction (RT-PCR). HBO increased the gene expression for both t-PA and PAI-1. CONCLUSIONS: HBO affects endothelial cell function and its fibrinolytic response. These findings may have clinical relevance in hyperbaric medicine and trauma care.

Dire straits.

Orthotics, the Cinderella of the NHS, needs a radical restructuring if it is to give patients the best serviice, argue Peter Bowker and colleagues.

Measurement validity in physical therapy research.

This article considers the role of measurement validity within physical therapy research. The concept of measurement validity is identified as a component of internal validity, and it is differentiated from the notion of reliability; these concepts are related to systematic and random sources of error, respectively. Using examples from physical therapy and rehabilitation, four main types of validity are reviewed: face validity, criterion-related validity, content validity, and construct validity. The differing implications of these types of validity for quantitative and qualitative research are discussed. Three principal areas of concern are then addressed, based on a critical discussion of selected examples from the literature. First, it is argued that validity is often poorly distinguished from the allied concept of reliability and that purported claims for validity often only demonstrate reliability. Second, it is claimed that validity is too often neglected in favor of reliability, and specific examples relating to gait analysis are put forward to support this argument. Third, some of the methodological difficulties that may occur when attempts are made to demonstrate validity are considered. The article concludes with a plea for a closer focus on the issue of measurement validity within physical therapy research.

Running to the taste of salt in mineralocorticoid-treated rats.

In the present series of studies, the running speed of rats in a runway was used to measure appetitive motivation for different concentrations of salt solutions. We found that when rats were thirsty, they were not interested in running for concentrated salt solutions; when they were rendered salt hungry by mineralocorticoid treatment in addition to the thirst, or even without thirst, they ran vigorously for salty tasting solutions, as high as 24% NaCl. The running speed is correlated with the degree of the mineralocorticoid treatment and the salt concentration. Moreover, drinking 5 cc of a 3% NaCl solution before the runway test decreases the running speed of the mineralocorticoid-treated rat. The experiments are discussed in the context of the effects of hormonal events on the movitation to ingest salt solutions.