Corticotherapy for traumatic brain-injured Patients - The Corti-TC trial: study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Traumatic brain injury (TBI) is a main cause of severe prolonged disability of young patients. Hospital acquired pneumonia (HAP) add to the morbidity and mortality of traumatic brain-injured patients. In one study, hydrocortisone for treatment of traumatic-induced corticosteroid insufficiency (CI) in multiple injured patients has prevented HAP, particularly in the sub-group of patients with severe TBI. Fludrocortisone is recommended in severe brain-injured patients suffering from acute subarachnoid hemorrhage. Whether an association of hydrocortisone with fludrocortisone protects from HAP and improves neurological recovery is uncertain. The aim of the current study is to compare corticotherapy to placebo for TBI patients with CI.</p> <p>Methods</p> <p>The CORTI-TC (Corticotherapy in traumatic brain-injured patients) trial is a multicenter, randomized, placebo controlled, double-blind, two-arms study. Three hundred and seventy six patients hospitalized in Intensive Care Unit with a severe traumatic brain injury (Glasgow Coma Scale ≤ 8) are randomized in the first 24 hours following trauma to hydrocortisone (200 mg.day^-1for 7 days, 100 mg on days 8-9 and 50 mg on day-10) with fludrocortisone (50 μg for 10 days) or double placebo. The treatment is stopped if patients have an appropriate adrenal response. The primary endpoint is HAP on day-28. The endpoint of the ancillary study is the neurological status on 6 and 12 months.</p> <p>Discussion</p> <p>The CORTI-TC trial is the first randomized controlled trial powered to investigate whether hydrocortisone with fludrocortisone in TBI patients with CI prevent HAP and improve long term recovery.</p> <p>Trial registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT01093261">NCT01093261</a></p

CpG-ODN and MPLA Prevent Mortality in a Murine Model of Post-Hemorrhage-Staphyloccocus aureus Pneumonia

Infections are the most frequent cause of complications in trauma patients. Post-traumatic immune suppression (IS) exposes patients to pneumonia (PN). The main pathogen involved in PN is Methicillin Susceptible Staphylococcus aureus (MSSA). Dendritic cells () may be centrally involved in the IS. We assessed the consequences of hemorrhage on pneumonia outcomes and investigated its consequences on DCs functions. A murine model of hemorrhagic shock with a subsequent MSSA pneumonia was used. Hemorrhage decreased the survival rate of infected mice, increased systemic dissemination of sepsis and worsened inflammatory lung lesions. The mRNA expression of Tumor Necrosis Factor-alpha (TNF-α), Interferon-beta (IFN-β) and Interleukin (IL)-12p40 were mitigated for hemorrhaged-mice. The effects of hemorrhage on subsequent PN were apparent on the pDCs phenotype (reduced MHC class II, CD80, and CD86 molecule membrane expression). In addition, hemorrhage dramatically decreased CD8+ cDCs- and CD8- cDCs-induced allogeneic T-cell proliferation during PN compared with mice that did not undergo hemorrhage. In conclusion, hemorrhage increased morbidity and mortality associated with PN; induced severe phenotypic disturbances of the pDCs subset and functional alterations of the cDCs subset. After hemorrhage, a preventive treatment with CpG-ODN or Monophosphoryl Lipid A increased transcriptional activity in DCs (TNF-α, IFN-β and IL-12p40) and decreased mortality of post-hemorrhage MSSA pneumonia

Characteristics and efficacy of early psycho­logical interventions in children and adolescents after single trauma: a meta-analysis

Background: Single traumatising events are associated with an elevated rate of psychological disorders in children and adolescents. To date, it remains unclear whether early psychological interventions can reduce longer term psychological maladjustment. Objective: To systematically review the literature to determine the characteristics and efficacy of early psychological interventions in children and adolescents after a single, potentially-traumatising event. Design: Systematic searches were conducted of all relevant bibliographic databases. Studies on early psychological interventions were included if the first session was conducted within 1 month of the event. Two independent observers assessed each study for eligibility, using pre-determined inclusion and exclusion criteria, and rated the study’s methodological quality. A meta-analysis was conducted on the group effects between individuals allocated to intervention versus control groups. Hence, effect sizes (ES) and confidence intervals were computed as well as heterogeneity and analogue-to-the ANOVA analyses. Results: Seven studies (including four randomised controlled trials) met the inclusion criteria. Depending on the specific outcome variable (e.g., dissociation, anxiety and arousal), small to large beneficial ES were noted. Although the meta-analysis revealed unexplained heterogeneity between the ES of the included studies, and although studies varied greatly with regards to their methodological quality and the interventions tested, findings suggest that early interventions should involve psycho-education, provide individual coping-skills and probably involve some kind of trauma exposure. Also, a stepped procedure that includes an initial risk screen and the provision of multiple sessions to those children at risk may be a promising strategy. Conclusions: To date, research on the effectiveness of early interventions in children after a potentially traumatising event remains scarce. However, our review suggests that early interventions may be helpful

A case-control study on risk factors for early-onset respiratory tract infection in patients admitted in ICU

<p>Abstract</p> <p>Background</p> <p>Respiratory tract infections are common in intensive care units (ICU), with incidences reported from 10 to 65%, and case fatality rates over 20% in pneumonia. This study was designed to identify risk factors for the development of an early onset respiratory tract infection (ERI) and to review the microbiological profile and the effectiveness of first intention antibiotic therapy.</p> <p>Methods</p> <p>Case-control, retrospective clinical study of the patients admitted to the Intensive Care Unit (ICU) of our hospital, a teaching and tertiary care facility, from January to September 2000 who had a respiratory tract infection diagnosed in the first 5 days of hospital stay.</p> <p>Results</p> <p>Of the 385 patients admitted to our unit: 129 (33,5%) had a diagnosis of ERI and 86 patients were admitted to the control group. Documented aspiration (adjusted OR = 5,265; 95% CI = 1,155 – 24,007) and fractured ribs (adjusted OR = 12,150; 95% CI = 1,571 – 93,941) were found to be independent risk factors for the development of ERI (multiple logistic regression model performed with the diagnostic group as dependent variable and adjusted for age, sex, SAPS II, documented aspiration, non-elective oro-tracheal intubation (OTI), fractured ribs, pneumothorax and pleural effusion).</p> <p>A total of 78 organisms were isolated in 61 patients (47%). The normal flora of the upper airway (<it>Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenza </it>and <it>Moraxella catharralis</it>) accounted for 72% of all isolations achieved, polimicrobian infections were responsible for 25% of all microbiological documented infections. First intention treatment was, in 62% of the patients, the association amoxacillin+clavulanate, being effective in 75% of the patients to whom it was administered.</p> <p>The patients with ERI needed more days of OTI (6 vs 2, p < 0,001) and mechanical ventilation (6 vs 2, p < 0,001) and had a longer ICU (7 vs 2, p < 0,001) and hospital length of stay (17 vs 11, p = 0,018), when compared with controls.</p> <p>Conclusion</p> <p>In this study documented tracheobronchial aspiration and fractured ribs were identified as independent risk factors for ERI. Microbiological profile was dominated by sensitive micro-organisms. The choice amoxacilin+clavulanate revealed to be a good option with an effectiveness rate of 77% in the patients in whom it was used.</p