Is cytomegalovirus reactivation increasing the mortality of patients with severe sepsis?

Cytomegalovirus (CMV) is a ubiquitous virus present in approximately two-thirds of the healthy population. This virus rarely causes an active disease in healthy individuals, but it is among the most common opportunistic infections in immunocompromised patients such as solid organ transplant recipients, patients receiving chemotherapy for cancer or patients with human immunodeficiency virus. Critically ill patients who are immunocompetent before intensive care unit admission may also become more prone to develop active CMV infection if they have prolonged hospitalizations, high disease severity, and severe sepsis. The development of active CMV infection in these critically ill patients has been associated with a significantly higher risk of death in several previous studies. The present issue of Critical Care brings a new study by Heininger and colleagues in which the authors found that patients with severe sepsis who developed active CMV infection had significantly longer intensive care unit and hospital stays, prolonged mechanical ventilation, but no changes in mortality compared to patients without CMV infection. We discuss the possible reasons for their findings (for example, selection bias and low (20%) statistical power to detect mortality endpoints), and also perform an update of our previous meta-analysis with the addition of Heininger and colleagues' study to verify whether the higher mortality rate with CMV holds. Our updated meta-analysis with approximately 1,000 patients shows that active CMV infection continues to be associated with a significant 81% higher mortality rate than that in critically ill patients without active CMV infection

Treatment of hospital-acquired pneumonia with linezolid or vancomycin: a systematic review and meta-analysis

Objective: Hospital-acquired pneumonia remains the most lethal and expensive nosocomial infection worldwide. Optimal therapy remains controversial. We aimed to compare mortality and clinical response outcomes in patients treated with either linezolid or vancomycin. Design: Systematic review and meta-analysis. Data sources PubMed, EMBASE, Cochrane Library, American College of Physicians Journal Club, Evidence-based Medicine BMJ and abstracts from infectious diseases and critical care meetings were searched through April 2013. Eligibility criteria for selecting studies All randomised clinical trials comparing linezolid to vancomycin for hospital-acquired pneumonia. Data extraction Preferred reporting items for systematic reviews and meta-analyses guidelines were followed. One author extracted the data and two authors rechecked and verified all data. Results: Nine randomised trials with a total of 4026 patients were included. The adjusted absolute mortality risk difference (RD) between linezolid and vancomycin was 0.01% (95% CI −2.1% to 2.1%; p=0.992; I2=13.5%. The adjusted absolute clinical response difference was 0.9% (95% CI −1.2% to 3.1%; p=0.409; I2=0%. The risk of both microbiological (RD=5.6%, 95% CI −2.2% to 13.3%; p=0.159; I2=0%) and methicillin-resistant Staphylococcus aureus (RD=6.4%, 95% CI −4.1% to 16.9%; p=0.230; I2=0%) eradication were not different between linezolid and vancomycin. Gastrointestinal side effects were more frequent with linezolid (RD=0.8% (95% CI 0% to 1.5%; p=0.05), but no differences were found with renal failure, thrombocytopenia and drug discontinuation due to adverse events. Our sample size provided 99.9% statistical power to detect differences between drugs regarding clinical response and mortality. Conclusions: Linezolid and vancomycin have similar efficacy and safety profiles. The high statistical power and the near-zero efficacy difference between both antibiotics demonstrates that no drug is superior for the treatment of hospital-acquired pneumonia

guide to clinicians

Funding This work received an unrestricted grant from GSK Portugal and was supported by Sociedade Portuguesa de Ginecologia (SPG).Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. In this context, biomarkers could be considered as indicators of either infection or dysregulated host response or response to treatment and/or aid clinicians to prognosticate patient risk. More than 250 biomarkers have been identified and evaluated over the last few decades, but no biomarker accurately differentiates between sepsis and sepsis-like syndrome. Published data support the use of biomarkers for pathogen identification, clinical diagnosis, and optimization of antibiotic treatment. In this narrative review, we highlight how clinicians could improve the use of pathogen-specific and of the most used host-response biomarkers, procalcitonin and C-reactive protein, to improve the clinical care of patients with sepsis. Biomarker kinetics are more useful than single values in predicting sepsis, when making the diagnosis and assessing the response to antibiotic therapy. Finally, integrated biomarker-guided algorithms may hold promise to improve both the diagnosis and prognosis of sepsis. Herein, we provide current data on the clinical utility of pathogen-specific and host-response biomarkers, offer guidance on how to optimize their use, and propose the needs for future research.publishersversionepub_ahead_of_prin

Immunogenicity and Reactogenicity of 2009 Influenza A (H1N1) Inactivated Monovalent Non-Adjuvanted Vaccine in Elderly and Immunocompromised Patients

Background\ud \ud Immunosuppressed individuals present serious morbidity and mortality from influenza, therefore it is important to understand the safety and immunogenicity of influenza vaccination among them.\ud Methods\ud \ud This multicenter cohort study evaluated the immunogenicity and reactogenicity of an inactivated, monovalent, non-adjuvanted pandemic (H1N1) 2009 vaccine among the elderly, HIV-infected, rheumatoid arthritis (RA), cancer, kidney transplant, and juvenile idiopathic arthritis (JIA) patients. Participants were included during routine clinical visits, and vaccinated according to conventional influenza vaccination schedules. Antibody response was measured by the hemagglutination-inhibition assay, before and 21 days after vaccination.\ud Results\ud \ud 319 patients with cancer, 260 with RA, 256 HIV-infected, 149 elderly individuals, 85 kidney transplant recipients, and 83 with JIA were included.\ud \ud The proportions of seroprotection, seroconversion, and the geometric mean titer ratios postvaccination were, respectively: 37.6%, 31.8%, and 3.2 among kidney transplant recipients, 61.5%, 53.1%, and 7.5 among RA patients, 63.1%, 55.7%, and 5.7 among the elderly, 59.0%, 54.7%, and 5.9 among HIV-infected patients, 52.4%, 49.2%, and 5.3 among cancer patients, 85.5%, 78.3%, and 16.5 among JIA patients. The vaccine was well tolerated, with no reported severe adverse events.\ud Conclusions\ud \ud The vaccine was safe among all groups, with an acceptable immunogenicity among the elderly and JIA patients, however new vaccination strategies should be explored to improve the immune response of immunocompromised adult patients. (ClinicalTrials.gov, NCT01218685)Fundação Butantan funded the study, and employed several of the authors. The funder had a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Relato sobre o desenvolvimento de modelos para obtenção automática do conteúdo de sites sobre saúde

Este relato técnico descreve o desenvolvimento de modelos, técnicas e protótipos para localização, padronização e extração automática do conteúdo apresentado em sites/páginas web com assuntos relacionados à área da saúde, visando à estimativa da qualidade destes sites/páginas extraídos. As técnicas e propostas descritas neste documento foram desenvolvidas ao longo do primeiro semestre de 2009 pelos alunos da disciplina CMPl12 - Sistemas de Informação Distribuídos do Programa de Pós-Graduação do Instituto de Informática da Universidade Federal do Rio Grande do Sul, ministrada pelo Professor Dr. José Palazzo Moreira de Oliveira. Cada uma das tarefas descritas aplicou técnicas e tecnologias diferentes para o seu desenvolvimento, apresentando resultados de diferentes naturezas, como tabelas, protótipos e modelos. Entretanto, todas foram desenvolvidas em busca do mesmo objetivo: a extração automática do conteúdo de sites/páginas que tratam sobre o tema "Doença de Alzheimer". Ao final to trabalho, obteve-se um conjunto de resultados, os quais serão utilizados para possibilitar a realização de estimativas a respeito da qualidade dos sites/páginas extraídos, de acordo com métricas de qualidade definidas.This report describes the development of models, techniques and prototypes to location, standardization and automatic extraction of content presented in web sites/pages with subject related to health, objecting estimate its quality. The techniques and proposals described here was performed during the first half of 2009 by students of the lecture CMP112 – Distributed Information Systems of Institute of Informatics of Federal University of Rio Grande do Sul, conducted by Professor Dr. José Palazzo Moreira de Oliveira. Each one of the tasks described in this report used different techniques and technologies for their development, presenting results of different natures, such as tables, prototypes and models. However, all tasks were developed looking for the same objective: the automatic extraction of content from web sites/pages related with the subject “Alzheimer’s Disease”. At the end of the work, we obtained a set of results, which will be used to enable the development of estimative concerning the quality of extracted web sites/pages, according with defined quality metrics

Why Are Clinicians Not Embracing the Results from Pivotal Clinical Trials in Severe Sepsis? A Bayesian Analysis

BACKGROUND: Five pivotal clinical trials (Intensive Insulin Therapy; Recombinant Human Activated Protein C [rhAPC]; Low-Tidal Volume; Low-Dose Steroid; Early Goal-Directed Therapy [EGDT]) demonstrated mortality reduction in patients with severe sepsis and expert guidelines have recommended them to clinical practice. Yet, the adoption of these therapies remains low among clinicians. OBJECTIVES: We selected these five trials and asked: Question 1--What is the current probability that the new therapy is not better than the standard of care in my patient with severe sepsis? Question 2--What is the current probability of reducing the relative risk of death (RRR) of my patient with severe sepsis by meaningful clinical thresholds (RRR >15%; >20%; >25%)? METHODS: Bayesian methodologies were applied to this study. Odds ratio (OR) was considered for Question 1, and RRR was used for Question 2. We constructed prior distributions (enthusiastic; mild, moderate, and severe skeptic) based on various effective sample sizes of other relevant clinical trials (unfavorable evidence). Posterior distributions were calculated by combining the prior distributions and the data from pivotal trials (favorable evidence). MAIN FINDINGS: Answer 1--The analysis based on mild skeptic prior shows beneficial results with the Intensive Insulin, rhAPC, and Low-Tidal Volume trials, but not with the Low-Dose Steroid and EGDT trials. All trials' results become unacceptable by the analyses using moderate or severe skeptic priors. Answer 2--If we aim for a RRR>15%, the mild skeptic analysis shows that the current probability of reducing death by this clinical threshold is 88% for the Intensive Insulin, 62-65% for the Low-Tidal Volume, rhAPC, EGDT trials, and 17% for the Low-Dose Steroid trial. The moderate and severe skeptic analyses show no clinically meaningful reduction in the risk of death for all trials. If we aim for a RRR >20% or >25%, all probabilities of benefits become lower independent of the degree of skepticism. CONCLUSIONS: Our clinical threshold analysis offers a new bedside tool to be directly applied to the care of patients with severe sepsis. Our results demonstrate that the strength of evidence (statistical and clinical) is weak for all trials, particularly for the Low-Dose Steroid and EGDT trials. It is essential to replicate the results of each of these five clinical trials in confirmatory studies if we want to provide patient care based on scientifically sound evidence

Genetic susceptibility to Chagas disease cardiomyopathy: involvement of several genes of the innate immunity and chemokine-dependent migration pathways

Abstract\ud \ud Background\ud Chagas disease, caused by the protozoan Trypanosoma cruzi is endemic in Latin America. Thirty percent of infected individuals develop chronic Chagas cardiomyopathy (CCC), an inflammatory dilated cardiomyopathy that is, by far, the most important clinical consequence of T. cruzi infection. The others remain asymptomatic (ASY). A possible genetic component to disease progression was suggested by familial aggregation of cases and the association of markers of innate and adaptive immunity genes with CCC development. Migration of Th1-type T cells play a major role in myocardial damage.\ud \ud \ud Methods\ud Our genetic analysis focused on CCR5, CCL2 and MAL/TIRAP genes. We used the Tag SNPs based approach, defined to catch all the genetic information from each gene. The study was conducted on a large Brazilian population including 315 CCC cases and 118 ASY subjects.\ud \ud \ud Results\ud The CCL2rs2530797A/A and TIRAPrs8177376A/A were associated to an increase susceptibility whereas the CCR5rs3176763C/C genotype is associated to protection to CCC. These associations were confirmed when we restricted the analysis to severe CCC, characterized by a left ventricular ejection fraction under 40%.\ud \ud \ud Conclusions\ud Our data show that polymorphisms affecting key molecules involved in several immune parameters (innate immunity signal transduction and T cell/monocyte migration) play a role in genetic susceptibility to CCC development. This also points out to the multigenic character of CCC, each polymorphism imparting a small contribution. The identification of genetic markers for CCC will provide information for pathogenesis as well as therapeutic targets.FAPES