Clinical Developments for Treating ARDS

Expert Opinion on Investigational Drugs. Jan, 2002  |  Pubmed ID: 11772319

Acute respiratory distress syndrome (ARDS), is characterised by capillary permeability and pulmonary oedema formation and may complicate a variety of medical and surgical illnesses. As a self-perpetuating state of inflammatory derangement, acute lung injury (ALI)/ARDS is manifest clinically as rapid development of radiographic infiltrates, severe hypoxaemia and reduced lung compliance. Over the years, researchers have made significant progress in elucidating the pathophysiology of this complex syndrome. Therapies targeting specific pathophysiologic steps in the development or persistence of this syndrome are in various stages of laboratory and clinical testing. Results to date have shown nitric oxide (NO) to improve oxygenation in the majority of patients but fail to improve mortality. Surfactant replacement has had limited success in adults, but new formulations and delivery methods may prove beneficial. Several inflammatory mediator-targeted therapies have progressed successfully through early clinical evaluation. Among these, neutrophil elastase inhibitors have shown the most promise and are currently undergoing Phase III trials. Other mediator-targeted therapies, such as prostaglandin E1, IL-10 and platelet activating factor antagonists, have not been found efficacious in large clinical trials of ARDS. However, these therapies, along with coagulation modulators, may have a favourable impact on ARDS by improving outcomes in sepsis, the greatest risk factor for developing this condition. In the interim, supportive care through improvements in mechanical ventilation are beneficial, while specific fluid balance and nutrition strategies may prove advantageous.

Albumin and Furosemide Therapy in Hypoproteinemic Patients with Acute Lung Injury

Critical Care Medicine. Oct, 2002  |  Pubmed ID: 12394941

Hypoproteinemia, fluid retention, and weight gain are associated with development of acute lung injury and mortality in critically ill patients, without proof of cause and effect. We designed a clinical trial to determine whether diuresis and colloid replacement in hypoproteinemic patients with acute lung injury would improve pulmonary physiology.

Findings on the Portable Chest Radiograph Correlate with Fluid Balance in Critically Ill Patients

Chest. Dec, 2002  |  Pubmed ID: 12475852

Fluid balance concerns occur daily in critically ill patients, complicated by difficulties assessing intravascular volume. Chest radiographs (CXRs) quantify pulmonary edema in acute lung injury (ALI) and total blood volume in normal subjects. We hypothesized that CXRs would reflect temporal changes in fluid balance in critically ill patients.

Crystal Ball for Acute Lung Injury Prognosis: Filled with Surfactant?

Critical Care Medicine. Jan, 2003  |  Pubmed ID: 12545037

The Epidemiology of Sepsis in the United States from 1979 Through 2000

The New England Journal of Medicine. Apr, 2003  |  Pubmed ID: 12700374

Sepsis represents a substantial health care burden, and there is limited epidemiologic information about the demography of sepsis or about the temporal changes in its incidence and outcome. We investigated the epidemiology of sepsis in the United States, with specific examination of race and sex, causative organisms, the disposition of patients, and the incidence and outcome.

Pro/con Clinical Debate: Hydroxyethylstarches Should Be Avoided in Septic Patients

Critical Care (London, England). Aug, 2003  |  Pubmed ID: 12930549

Androgen Control of Cell Proliferation and Cytoskeletal Reorganization in Human Fibrosarcoma Cells: Role of RhoB Signaling

The Journal of Biological Chemistry. Jan, 2004  |  Pubmed ID: 14576147

We recently generated an HT-1080-derived cell line called HT-AR1 that responds to dihydrotestosterone (DHT) treatment by undergoing cell growth arrest in association with cytoskeletal reorganization and induction of neuroendocrine-like cell differentiation. In this report, we show that DHT induces a dose-dependent increase in G0/G1 growth-arrested cells using physiological levels of hormone. The arrested cells increase in cell size and contain a dramatic redistribution of desmoplakin, keratin 5, and chromogranin A proteins. DHT-induced cytoskeletal changes were also apparent from time lapse video microscopy that showed that androgen treatment resulted in the rapid appearance of neuronal-like membrane extensions. Expression profiling analysis using RNA isolated from DHT-treated HT-AR1 cells revealed that androgen receptor activation leads to the coordinate expression of numerous cell signaling genes including RhoB, PTGF-beta, caveolin-2, Egr-1, myosin 1B, and EHM2. Because RhoB has been shown to have a role in tumor suppression and neuronal differentiation in other cell types, we investigated RhoB signaling functions in the HT-AR1 steroid response. We found that steroid induction of RhoB was DHT-specific and that newly synthesized RhoB protein was post-translationally modified and localized to endocytic vesicles. Moreover, treatment with a farnesyl transferase inhibitor reduced DHT-dependent growth arrest, suggesting that prenylated RhoB might function to inhibit HT-AR1 cell proliferation. This was directly shown by transfecting HT-AR1 cells with RhoB coding sequences containing activating or dominant negative mutations.

Web-based Interventions for Substance Use Disorders: a Qualitative Review

Journal of Substance Abuse Treatment. Mar, 2004  |  Pubmed ID: 15050088

Substance use disorder is one of the most common mental health problems in the Western world with a significant contribution to the global burden of disease and a high level of unmet treatment need. To assess the use and effectiveness of web-based interventions for substance use disorders. A qualitative review of the published literature across databases Medline, EMBASE, PsychINFO, GrayLIT Network, and Web of Science using relevant key terms. A search of the worldwide web was also conducted using search engines such as Google. There were a number of computerized and internet-based interventions for mental health disorders including substance use disorders located; however, they are largely descriptive with no large randomized controlled trials of internet-delivered interventions for substance use disorders reported. While the literature on internet-based substance use interventions is sparse and flawed, the potential impact of effective intervention is considerable. On the basis of the limited research available it is reasonable to suggest that a demand for such interventions exists and there is a likelihood that they would be as effective as those delivered by therapists for the majority of less severely dependent clients. Further clinical outcome research, particularly in the area of brief interventions for alcohol use disorders and extension to other drugs such as cannabis and club drugs, is certainly justified. (c) 2004 Elsevier Science Inc. All rights reserved.

Albumin Influences Total Plasma Antioxidant Capacity Favorably in Patients with Acute Lung Injury

Critical Care Medicine. Mar, 2004  |  Pubmed ID: 15090958

To ascertain the influence of albumin on antioxidant status in patients with acute lung injury.

Understanding and Managing Fluid Balance in Patients with Acute Lung Injury

Current Opinion in Critical Care. Feb, 2004  |  Pubmed ID: 15166844

Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) affect hundreds of thousands of people each year worldwide, resulting in a significant healthcare burden. Over the past four decades, much has been discovered regarding the pathophysiology of lung injury, yet little progress has been made in advancing effective treatment strategies. In this article, we discuss the current knowledge as to fluid balance in the pathophysiology of ALI/ARDS and the recent innovations that have been described related to manipulations of hydrostatic or oncotic pressure in this condition.

The Two-headed Swan

MedGenMed : Medscape General Medicine. 2004  |  Pubmed ID: 15266235

Pulmonary artery catheterization is a frequent procedure for hemodynamic monitoring in critically ill patients or high-risk surgical patients. Mechanical and infectious complications are recognized, though catheter dysfunction and malposition are more frequent and often require clinical intervention. We present the case of a Swan-Ganz catheter with the appearance of a mechanical fracture at the distal end, which required clinical and radiographic investigation to determine the nature of the aberrancy. The evaluation of a malfunctioning pulmonary artery catheter (PAC) is a frequent occurrence in the intensive care unit and requires careful clinical consideration and radiographic examination.

Fluid Management in Shock

Seminars in Respiratory and Critical Care Medicine. Dec, 2004  |  Pubmed ID: 16088510

Shock is a broad category of injury to the human body caused by a variety of insults. Fluid resuscitation is the cornerstone of initial therapy for nearly all forms of shock. This article reviews the basic physiology determining body fluid composition, the goals of fluid resuscitation in shock, the types of fluids available for use, and clinical evidence for use of specific fluids based on etiology of the insult.

A Randomized, Controlled Trial of Furosemide with or Without Albumin in Hypoproteinemic Patients with Acute Lung Injury

Critical Care Medicine. Aug, 2005  |  Pubmed ID: 16096441

Hypoproteinemia is a common condition in critically ill patients, associated with the development of acute lung injury and acute respiratory distress syndrome and subsequent worse clinical outcomes. Albumin with furosemide benefits lung physiology in hypoproteinemic patients with acute lung injury/acute respiratory distress syndrome, but the independent pharmacologic effects of these drugs are unknown.

Temporal Changes in Clinical Outcomes with ARDS

Chest. Aug, 2005  |  Pubmed ID: 16100125

Epidemiology of Sepsis: Recent Advances

Current Infectious Disease Reports. Sep, 2005  |  Pubmed ID: 16107228

Sepsis, as defined by an expert consensus definition, is the development of the systemic inflammatory response syndrome in the presence of infection. Using this clinically applicable definition, several studies have evaluated the epidemiology of sepsis over the past decade. The current incidence of sepsis is at least 240 patients per 100,000 people in the United States population, whereas for severe sepsis it is between 51 and 95 patients per 100,000 people. The incidence rate for sepsis has been increasing over the past two decades, driving an increase in the number of deaths despite a decline in case-fatality rates. Sepsis is the tenth leading cause of death in the United States and accounts for more than 17 billion dollars in direct healthcare expenditures.

The Adolescent Cannabis Check-Up: Feasibility of a Brief Intervention for Young Cannabis Users

Journal of Substance Abuse Treatment. Oct, 2005  |  Pubmed ID: 16183469

In this study, we assessed the feasibility and effectiveness of the Adolescent Cannabis Check-Up (ACCU), a brief intervention for young cannabis users. For this initial feasibility study, we used an uncontrolled pre-test/post-test design. Participants were cannabis users aged between 14 and 19 years (n = 73) and concerned parents (n = 69). The intervention comprised an individual assessment session followed 1 week later by a session of personalized feedback delivered in a motivational interviewing style. An optional third session that focused on skills and strategies for making behavioral change was offered. Of the entire sample of cannabis users, 78% reported voluntarily reducing or stopping their cannabis use during the 90 days to follow-up and 16.7% reported total abstinence during this time. In addition, significant reductions were found on measures of both quantity and frequency of use and dependence. These reductions were maintained at 6-month follow-up. Clearly, these preliminary findings must be interpreted with caution given the study design and absence of a control group. The ACCU was, however, able to attract and retain young cannabis users who were not necessarily interested in change. The approach was acceptable to young people and associated with reductions in cannabis use. It appears to be a model that warrants further research in early and brief interventions for this population.

Online Enrollment in Medicaid and SCHIP

NCSL Legisbrief. Feb, 2005  |  Pubmed ID: 15724319

Extravascular Lung Water in Patients with Severe Sepsis: a Prospective Cohort Study

Critical Care (London, England). Apr, 2005  |  Pubmed ID: 15774053

Few investigations have prospectively examined extravascular lung water (EVLW) in patients with severe sepsis. We sought to determine whether EVLW may contribute to lung injury in these patients by quantifying the relationship of EVLW to parameters of lung injury, to determine the effects of chronic alcohol abuse on EVLW, and to determine whether EVLW may be a useful tool in the diagnosis of acute respiratory distress syndrome (ARDS).

Globalization and Health

Globalization and Health. Apr, 2005  |  Pubmed ID: 15847699

This debut editorial of Globalization and Health introduces the journal, briefly delineating its goals and objectives and outlines its scope of subject matter. 'Open Access' publishing is expected to become an increasingly important format for peer reviewed academic journals and that Globalization and Health is 'Open Access' is appropriate. The rationale behind starting a journal dedicated to globalization and health is three fold:Firstly: Globalization is reshaping the social geography within which we might strive to create health or prevent disease. The determinants of health - be they a SARS virus or a predilection for fatty foods - have joined us in our global mobility. Driven by economic liberalization and changing technologies, the phenomenon of 'access' is likely to dominate to an increasing extent the unfolding experience of human disease and wellbeing.Secondly: Understanding globalization as a subject matter itself needs certain benchmarks and barometers of its successes and failings. Health is one such barometer. It is a marker of social infrastructure and social welfare and as such can be used to either sound an alarm or give a victory cheer as our interconnectedness hurts and heals the populations we serve.And lastly: In as much as globalization can have an effect on health, it is also true that health and disease has an effect on globalization as exemplified by the existence of quarantine laws and the devastating economic effects of the AIDS pandemic.A balanced view would propose that the effects of globalization on health (and health systems) are neither universally good nor bad, but rather context specific. If the dialogue pertaining to globalization is to be directed or biased in any direction, then it must be this: that we consider the poor first.

Albumin: Biochemical Properties and Therapeutic Potential

Hepatology (Baltimore, Md.). Jun, 2005  |  Pubmed ID: 15915465

Evolution of Treatments for Patients with Acute Lung Injury

Expert Opinion on Investigational Drugs. May, 2005  |  Pubmed ID: 15926869

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are acute life-threatening forms of hypoxemic respiratory failure. ALI/ARDS patients require intensive care with prolonged mechanical ventilation. Despite advances in our understanding of the pathophysiology of ALI/ARDS, mortality rates remain > 30% and survivors suffer significant decrements in their quality of life. The evolving understanding of ALI/ARDS and the complex interactions involved in ALI/ARDS open the door for many potential targets for treatment. The condition is characterised by an acute inflammatory state that leads to increased capillary permeability and accumulation of proteinaceous pulmonary oedema. The changes that occur as a result of this inflammation clinically manifest themselves as hypoxemia, infiltrates on chest radiograph and reduced lung compliance. Many years have been dedicated to analysing the complexities involved in ALI/ARDS in order to improve current and future possibilities for treatment, with the aim of improving patient outcomes. Although some therapies have demonstrated benefits of improved oxygenation, such as surfactant and nitric oxide, these benefits have not translated into reductions in the duration of mechanical ventilation or mortality. Inflammatory mediator-targeted therapies were promising early on; however, larger trials have found therapies such as cytokine modulation, platelet-activating factor inhibition and neutrophil elastase inhibitors to be ineffective in the treatment of ALI/ARDS. Preclinical studies with beta2-agonists and granulocyte macrophage colony-stimulating factor have shown promise for restoring alveolar capillary barrier integrity or reducing pulmonary oedema, and further studies are being conducted to test for true clinical benefit. Despite previous therapeutic failures, newer surfactant formulations have shown promise, particularly in patients with direct forms of lung injury, and are currently in Phase III trials. Anticoagulant therapy with activated protein C has been shown to improve survival in sepsis, the most common risk factor for the development of ALI/ARDS, and is now being studied in ALI/ARDS. Until new data emerge, the focus must remain on supportive care, including optimised mechanical ventilation, nutritional support, manipulation of fluid balance and prevention of intervening medical complications.

Pharmacological Aspects of Albumin As a Niche Product in the Intensive Care Unit

Critical Care Medicine. Jul, 2005  |  Pubmed ID: 16003093

Conflicting Clinical Trial Data: a Lesson from Albumin

Critical Care (London, England). 2005  |  Pubmed ID: 16356259

Albumin is a frequently prescribed drug in hospitalized patients, and its effect on clinical outcomes has been scrutinized in recent years. Data from meta-analyses has suggested harm related to albumin therapy in critically ill patients, and new observational data are consistent with these results. However, appropriately powered randomized, controlled trials have shown albumin to be safe in broad groups of critically ill patients. This article will discuss the reasons for differences between observational and controlled trial data, and the implications for future albumin use and clinical research.

The Role of Acute Blood Transfusion in the Development of Acute Respiratory Distress Syndrome in Patients with Severe Trauma

The Journal of Trauma. Sep, 2005  |  Pubmed ID: 16361918

Patients with major trauma necessitating the transfusion of packed red blood cells (PRBCs) are at increased risk for the acute respiratory distress syndrome (ARDS). However, it is presently unknown whether the amount of transfused blood is independently associated with development of ARDS in patients with severe trauma.

The Effect of Age on the Development and Outcome of Adult Sepsis

Critical Care Medicine. Jan, 2006  |  Pubmed ID: 16374151

Sepsis is an increasingly common and lethal medical condition that occurs in people of all ages. The influence of age on sepsis risk and outcome is incompletely understood. We sought to determine the independent effect of age on the incidence, severity, and outcome of adult sepsis.

Ancient Signals: Comparative Genomics of Plant MAPK and MAPKK Gene Families

Trends in Plant Science. Apr, 2006  |  Pubmed ID: 16537113

MAPK signal transduction modules play crucial roles in regulating many biological processes in plants, and their components are encoded by highly conserved genes. The recent availability of genome sequences for rice and poplar now makes it possible to examine how well the previously described Arabidopsis MAPK and MAPKK gene family structures represent the broader evolutionary situation in plants, and analysis of gene expression data for MPK and MKK genes in all three species allows further refinement of those families, based on functionality. The Arabidopsis MAPK nomenclature appears sufficiently robust to allow it to be usefully extended to other well-characterized plant systems.

Epidemiology Studies in Critical Care

Critical Care (London, England). 2006  |  Pubmed ID: 16606434

Epidemiology studies are an essential part of clinical research, often forming the foundation for studies ranked more highly in the hierarchy of evidence-based medicine. Studies of sepsis to date have been conducted on local, regional, national and international scales, with the majority conducted in the past 5 years. Longitudinal epidemiology studies convey an important additional aspect of the healthcare burden from disease, and may additionally serve to compare the effectiveness and efficiency of healthcare systems, to examine specific patient care strategies and to perform quality control analyses.

The Adolescent Cannabis Problems Questionnaire (CPQ-A): Psychometric Properties

Addictive Behaviors. Dec, 2006  |  Pubmed ID: 16626880

Despite the widespread use of cannabis among young people, little research attention has been given to the development of psychometrically sound measures specific to cannabis related problems in this group. The aim of this study was to explore the reliability, validity and factor structure of a multi-dimensional measure of cannabis-related problems among adolescents. The Adolescent Cannabis Problems Questionnaire (CPQ-A) was developed as an assessment tool and treatment outcome measure. A stratified sample of 100 young people (aged 14-18 years) who had used cannabis in the past 90 days were administered the CPQ-A on two occasions 1 week apart. Exploratory factor analysis revealed three factors accounting for 63% of total variance with alpha coefficients of 0.88, 0.72 and 0.73. The CPQ-A was reliable with test-retest correlation for the total CPQ-A being 0.91. CPQ-A score correlated significantly with frequency of cannabis use and number of DSM-IV dependence criteria reported. The findings show promise for the CPQ-A as a reliable, valid and potentially clinically useful measure of cannabis related problems among young people.

The Global Health Governance of Antimicrobial Effectiveness

Globalization and Health. 2006  |  Pubmed ID: 16638130

Antimicrobial resistance is a growing threat to public health the world over. Global health governance strategies need to address the erosion of antimicrobial effectiveness on three levels. Firstly, mechanisms to provide incentives for the pharmaceutical industry to develop antimicrobials for diseases threatening the developing world need to be sought out. Secondly, responsible use of antimicrobials by both clinicians and the animal food growing industry needs to be encouraged and managed globally. And lastly, in-country and international monitoring of changes in antimicrobial effectiveness needs to be stepped up in the context of a global health governance strategy.

The Epidemiology of Sepsis in Patients with Malignancy

Chest. Jun, 2006  |  Pubmed ID: 16778259

To evaluate the longitudinal epidemiology of sepsis in patients with a history of cancer and to specifically examine sepsis-related disparities in risk or outcome.

Brief Report: Tuberculosis Sepsis and Activated Protein C

The American Journal of the Medical Sciences. Jul, 2006  |  Pubmed ID: 16845244

The Role of Infection and Comorbidity: Factors That Influence Disparities in Sepsis

Critical Care Medicine. Oct, 2006  |  Pubmed ID: 16915108

Large healthcare disparities exist in the incidence of sepsis based on both race and gender. We sought to determine factors that may influence the occurrence of these healthcare disparities, with respect to the source of infection, causal organisms, and chronic comorbid medical conditions.

Sepsis: the Future is Bright

Critical Care Medicine. Sep, 2006  |  Pubmed ID: 16921317

A New Twist on Albumin Therapy in the Intensive Care Unit, Again

Critical Care Medicine. Oct, 2006  |  Pubmed ID: 16983266

The Role of Body Mass Index and Diabetes in the Development of Acute Organ Failure and Subsequent Mortality in an Observational Cohort

Critical Care (London, England). 2006  |  Pubmed ID: 16999863

Several studies have shown a correlation between body mass index (BMI) and both the development of critical illness and adverse outcomes in critically ill patients. The goal of our study was to examine this relationship prospectively with particular attention to the influence of concomitant diabetes mellitus (DM).

Serum Dioxin Levels in Former Chlorophenol Workers

Journal of Exposure Science & Environmental Epidemiology. Jan, 2006  |  Pubmed ID: 16015278

Using gas chromatography/mass spectrometry, we measured lipid-adjusted serum levels for all 2,3,7,8-substituted dioxins and furans, and four coplanar polychlorinated biphenyls in 62 workers with chlorophenol exposure and 36 workers without chlorophenol exposures working at the same plant during the same time. We oversampled among workers diagnosed with chloracne. Mean dioxin background levels from 36 nonchlorophenol workers were estimated as 6.0 parts-per-trillion (ppt) for 2,3,7,8 tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) and 67.5 ppt for 1,2,3,4,6,7,8 heptachlorodibenzo-p-dioxin (Hepta-CDD). We found different dioxin and furan profiles for trichlorophenol and pentachlorophenol (PCP) workers. Among trichlorophenol workers with chloracne, we found 2,3,7,8-TCDD (mean=30.5 ppt) above background levels and among PCP workers with chloracne, we found high levels of Hepta-CDD (mean=312.5 ppt) and other higher chlorinated dioxins and furans. Cumulative exposure estimates for dioxins for both 2,3,7,8-TCDD and the higher chlorinated dioxins created in the early 1980s for our epidemiology studies were highly correlated with serum dioxin levels when age and body mass index were taken into account. While workers previously diagnosed with chloracne had high serum dioxin levels, some workers without diagnosed chloracne also had high levels. Among tradesworkers with plant-wide responsibilities, we observed serum dioxins and PCB levels higher than background indicating workplace exposures. We estimate that the mean level of 2,3,7,8-TCDD present in the serum of workers on the date workplace exposure terminated was 267 ppt (ranging from 8 to 1184 ppt) assuming a 9-year half-life, 582 ppt (ranging from 10 to 2,641 ppt) assuming a 7-year half-life, and 1928 ppt (ranging from 22 to 17,847) when a toxicokinetic model is used. We conclude that our findings are consistent with other studies reporting high serum dioxin levels among chlorophenol workers after occupational exposures.

The Severity of Dependence Scale (SDS) in an Adolescent Population of Cannabis Users: Reliability, Validity and Diagnostic Cut-off

Drug and Alcohol Dependence. Jun, 2006  |  Pubmed ID: 16310973

The Severity of Dependence Scale (SDS) is a five-item scale that has been reported to be a reliable and valid screening instrument for dependence and a measure of dependence severity in adults across several substance classes. To date no data have been reported on its performance in a population of adolescent cannabis users. The current study assessed the psychometric properties of the SDS in a community sample of 14-18-year-old adolescent cannabis users (n=100). Internal consistency (alpha=0.83) and test-retest coefficients (ICC=0.88) were high and a principal components analysis of the scale found all items to load on a single factor. Total SDS score correlated significantly with frequency of cannabis use and number of DSM-IV dependence criteria met, indicating good concurrent validity. Receiver Operating Characteristic curve analysis was used to determine the most appropriate SDS cut-off score for use as an indicator of cannabis dependence, with optimal discrimination at an SDS score of 4. These findings indicate that the SDS is a reliable and valid measure of severity of cannabis dependence among adolescents, has high diagnostic utility, and that an SDS score of 4 may be indicative of cannabis dependence.

Alcohol Abuse and Acute Lung Injury: Can We Target Therapy?

Expert Review of Respiratory Medicine. Oct, 2007  |  Pubmed ID: 20477184

Recent studies have revealed an important but previously unrecognized association between alcohol abuse and the risk of acute respiratory distress syndrome (ARDS). This devastating form of lung injury strikes individuals of any age following insults, such as major trauma or sepsis, and even with state-of-the-art medical care it has a mortality as high as 50%. Although the precise incidence is unknown, it is estimated that 200,000 individuals develop ARDS each year in the USA alone. Alcohol abuse independently increases the risk approximately two- to fourfold and, therefore, causes tens of thousands of excess deaths annually. When one couples these grim estimates with the well-recognized association between alcohol abuse and severe lung infections, such as bacterial pneumonia and tuberculosis, it is apparent that alcohol-related lung diseases are a major public health problem. Exciting new studies reveal that the alcoholic lung is characterized by discrete changes in cellular function within the lower airways, mediated via oxidant stress and altered signaling pathways and, in experimental models, is highly amenable to targeted therapies. Furthermore, these therapies are already used clinically for other conditions and could readily be tested in clinical studies of alcoholics at high risk for ARDS and/or with severe lung infections. This article focuses on the epidemiology and pathophysiology of alcohol-induced lung dysfunction and discusses potential new treatments that are suggested by recent experimental findings.

Expanding the Global Epidemiology of Sepsis

Critical Care Medicine. Nov, 2007  |  Pubmed ID: 18075373

Sepsis and Sex: Can We Look Beyond Our Hormones?

Chest. Dec, 2007  |  Pubmed ID: 18079213

Nailing the Evidence

Chest. Dec, 2007  |  Pubmed ID: 18079247

Seasonal Variation in the Epidemiology of Sepsis

Critical Care Medicine. Feb, 2007  |  Pubmed ID: 17167351

We sought to investigate seasonal and regional variability in the epidemiology of sepsis and to identify underlying associations based on geography and seasonal viral infections. Understanding seasonal or regional variations may improve knowledge of sepsis epidemiology and pathophysiology and could affect healthcare planning and resource allocation.

Alcohol Dependence is Independently Associated with Sepsis, Septic Shock, and Hospital Mortality Among Adult Intensive Care Unit Patients

Critical Care Medicine. Feb, 2007  |  Pubmed ID: 17205003

To determine the association between alcohol dependence (alcoholism not in remission and/or alcohol withdrawal) and sepsis, septic shock, and hospital mortality among intensive care unit (ICU) patients.

Disparities in Sepsis: What Do We Understand?

Critical Care Medicine. Mar, 2007  |  Pubmed ID: 17421091

Serum Concentrations of Chlorinated Dibenzo-p-dioxins and Dibenzofurans Among Former Michigan Trichlorophenol and Pentachlorophenol Workers

Journal of Exposure Science & Environmental Epidemiology. Sep, 2007  |  Pubmed ID: 17426737

This study examines serum levels of 2,3,7,8-substituted chlorinated dioxins and furans, and PCBs for 375 Michigan workers with potential chlorophenol exposure, 37 Worker Referents, and 71 Community Referents. The chlorophenol workers were last exposed to trichlorophenol and/or pentachlorophenol 26-62 years ago. Employees working only in the trichlorophenol units had mean lipid-adjusted 2378-tetrachlorodibenzo-p-dioxin (TCDD) levels of 15.9 ppt compared with 6.5 ppt in the Worker Referents. Employees working only in the pentachlorophenol units had mean lipid-adjusted levels for 123478-H6CDD of 16.1 ppt, 123678-H6CDD of 150.6 ppt, 123789-H6CDD of 20.2 ppt, 1234678-H7CDD of 192.6 ppt, and OCDD of 2,594.0 ppt compared with the Worker Referent levels for the same congeners of 7.5, 74.7, 8.6, 68.7, and 509.1 ppt, respectively. All furan and PCB levels among workers in the trichlorophenol and/or pentachlorophenol departments were similar to the Worker Referents. The Tradesmen who worked throughout the plant had dioxin congener profiles consistent with both trichlorophenol and pentachlorophenol exposures. PCB levels and levels of 23478-P5CDF, 123478-H6CDF, and 123678-H6CDF were also greater in these Tradesmen than in the Worker Referents. The Worker Referent group had higher levels of dioxins and furans than the Community Referents indicating the potential for exposure outside the chlorophenol departments at the site. Distinct patterns of dioxin congeners were found many years after exposure among workers with different chlorophenol exposures. Furthermore, past trichlorophenol exposures were readily distinguishable from past pentachlorophenol exposures based on serum dioxin evaluations among workers. These data can be used to better assess dioxin exposures in future health studies.

Is Severe Sepsis Increasing in Incidence AND Severity?

Critical Care Medicine. May, 2007  |  Pubmed ID: 17446733

Balancing Intellectual Monopoly Privileges and the Need for Essential Medicines

Globalization and Health. 2007  |  Pubmed ID: 17565684

This issue of Globalization and Health presents a paper by Kerry and Lee that considers the TRIPS agreement and the recent policy debate regarding the protection of public health interest, particularly as they pertain to the Doha Declaration. In this editorial, we consider the debate, the conclusions thereof, and identify five questions that should be considered by key stakeholders in ongoing discussions.

Body Mass Index and Serum Chlorinated Dibenzo-p-dioxin and Dibenzofuran Levels

Chemosphere. Jan, 2007  |  Pubmed ID: 16919309

Several studies have found that current levels of 2,3,7,8 tetrachlorodibenzo-p-dioxin in serum lipids are related to age with older persons generally having higher levels. To account for this age pattern, reference ranges based on national samples have been established in order to allow determination of background levels for regional studies. In several studies, body mass index (BMI), has also been associated with current 2,3,7,8 tetrachlorodibenzo-p-dioxin levels with increasing body mass index related to increasing levels. We measured lipid-adjusted serum levels for all 2,3,7,8-substituted dioxins and furans in 62 chemical manufacturing workers with chlorophenol exposures and 36 workers without chlorophenol exposures employed at the same location. We then assessed the impact of age and BMI on the serum levels of all these compounds in the presence of other potential confounders. We found that both factors are important independent determinants of serum levels of 2,3,7,8-substituted dioxins and furans. Specifically, age and BMI are both important factors for assessing background levels of 2,3,7,8 tetrachlorodibenzo-p-dioxin, 1,2,3,7,8 pentachlorodibenzo-p-dioxin and the calculated total toxic equivalency. BMI, but not age, is important for assessing background levels of higher chlorinated dioxins and some hexachlorofurans. We conclude that age and BMI are both important considerations when comparing a potentially exposed group to a referent group, or to national norms. Further, age and BMI may also be important in epidemiology studies where back-extrapolation from current dioxin levels is used to assess historical chlorophenol exposure.

The Adolescent Cannabis Check-up: Randomized Trial of a Brief Intervention for Young Cannabis Users

Journal of Substance Abuse Treatment. Jun, 2008  |  Pubmed ID: 17869051

The aim of this study was to evaluate the efficacy of a brief motivational enhancement therapy in reducing cannabis use and cannabis-related problems in a population of non-treatment-seeking adolescent cannabis users. In a randomized controlled trial, 40 young people (aged 14-19 years) were randomly assigned to either a two-session brief intervention or a 3-month delayed-treatment control condition. The intervention consisted of a detailed assessment and a session of motivational enhancement therapy. An additional optional discussion of skills for reducing or quitting cannabis use was offered if a participant was interested in discussing these issues. Primary outcome measures were changes in days of cannabis use, mean quantity of cannabis used weekly, and number of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition dependence symptoms reported. Significantly greater reductions on these measures were found in the Adolescent Cannabis Check-up group at 3-month follow-up. Between-group effect sizes were moderate. The approach is acceptable to participants and merits further evaluation with this difficult to reach population.

Factors Related to Dioxin and Furan Body Levels Among Michigan Workers

Environmental Research. Feb, 2008  |  Pubmed ID: 18054905

We evaluated serum concentrations of five selected dioxin, furan, and polychlorinated biphenyls (PCB) congeners among 412 workers at a Midland, Michigan plant that manufactured trichlorophenol and pentachlorophenol (PCP) and formulated chlorophenol-based products. We examined occupational indicators of exposure to these chlorophenols taking into account intrinsic factors such as age and body fat and potential environmental sources of exposure from consumption of local game and fish and other occupations. All five congeners were significantly associated with age and body fat. 2378-TCDD serum concentrations were associated with trichlorophenol operations, total years employed at the plant, as well as working as a hazardous waste worker. 123678-H(6)CDD serum concentrations were related to occupational PCP exposure, chloracne, recent weight loss, eating local game, and working as a hazardous waste worker. Serum concentrations of PCB126 were related to smoking (inversely), and eating local fish or local game. Other factors such as diet and jobs outside of the chlorophenol plant exposures had only a very minor impact on dioxin and furan concentrations in these workers.

Systemic Inactivation of Hs6st1 in Mice is Associated with Late Postnatal Mortality Without Major Defects in Organogenesis

Genesis (New York, N.Y. : 2000). Jan, 2008  |  Pubmed ID: 18196599

Heparan sulfate (HS) proteoglycans modulate the biological activity of a number of growth factors in development, homeostasis, and cancer. Specific modifications of HS chains by HS biosynthetic enzymes have been implicated in growth factor signaling in multiple aspects of organogenesis. Although the role of HS 6-O-sulfotransferases has been described in processes such as trachea formation in Drosophila and vasculogenesis in zebrafish, little is known about how HS 6-O-sulfotransferases (Hs6st1-3 in mice) influence mouse development. To address this issue, we generated a conditionally mutant Hs6st1 mouse line and then generated mice with systemic inactivation of Hs6st1. Hs6st1-null pups were viable and grossly normal at birth. The lack of obvious abnormalities in lung, liver, and kidney, which express high levels of Hs6st1 during development, suggests that at least during embryonic life, the loss of Hs6st1 function may be compensated for by mechanisms involving other HS modifying enzymes. During early adulthood, however, Hs6st1-null mice failed to thrive and exhibited growth retardation, body weight loss, enlargement of airspaces in the lung and, in some cases, lethality. Our results suggest a potentially critical role for HS 6-O sulfation by Hs6st1 in postnatal processes.

Effect of Sepsis Therapies on Health-related Quality of Life

Critical Care (London, England). 2008  |  Pubmed ID: 18254930

Sepsis is one of the most common conditions encountered in the intensive care unit and is the 10th leading cause of death overall in the United States. Both long-term survival and health-related quality of life are reduced in survivors of sepsis, yet there is little knowledge of the effect of sepsis-specific interventions on either long-term survival or health-related quality of life. The present article discusses the importance of studying health-related quality of life as it relates to sepsis management strategies, particularly in the context of pharmacologic therapy with recombinant human activated protein C.

Chlorinated Dibenzo-p-dioxins, Dibenzofurans, and Biphenyl Profiles of Workers with Trichlorophenol and Pentachlorophenol Exposures

Chemosphere. Aug, 2008  |  Pubmed ID: 18442847

We examined the serum lipid adjusted levels of 2,3,7,8-substituted chlorinated dioxins and furans, and four coplanar PCBs for 98 workers. We found workers who worked only in the trichlorophenol units had mean lipid adjusted 2,3,7,8-TCDD levels of 36.8 ppt significantly higher (p<0.05) than 6.0 ppt in the reference group. Workers who worked only in the pentachlorophenol units had mean lipid adjusted levels for 123478-HxCDD of 14.8 ppt, 123678-HxCDD of 156.4 ppt,123789-HxCDD of 23.7 ppt, 1234678-HpCDD of 234.6 ppt, and OCDD of 2,778.2 ppt significantly higher (p<0.05) than the reference group levels for the same congeners of 7.5, 71.8, 8.0, 67.5, and 483.2 ppt, respectively. While we did find 12378-PeCDD levels higher than the reference group in trichlorophenol and pentachlorophenol workers, the differences are small, and could be attributed to normal variation. All furan levels among the trichlorophenol or pentachlorophenol only workers were not significantly different than the reference group. Workers with both trichlorophenol and pentachlorophenol exposures had mean dioxin levels consistent with complex chlorophenol exposures. Tradesmen who worked throughout the plant had congener profiles consistent with both trichlorophenol and pentachlorophenol exposures. PCB 169, 23478-PeCDF, 123478-HxCDF, and 123678-HxCDF levels were also significantly greater (p<0.05) in these tradesmen than in the reference group. We found distinct patterns of dioxin congeners many years after exposure among workers with different chlorophenol exposures. We were effectively able to distinguish past trichlorophenol exposures from pentachlorophenol exposures based on differing serum dioxin profiles among workers.

Monitoring of Endothelial Dysfunction in Critically Ill Patients: the Role of Endothelial Progenitor Cells

Current Opinion in Critical Care. Jun, 2008  |  Pubmed ID: 18467899

This review provides an overview of sepsis as a prototypical critical illness and discusses the role of the endothelium in the pathophysiology of sepsis and sepsis-related organ dysfunction, the characterization and functions of endothelial progenitor cells, and investigates these cells both as a prognostic and therapeutic strategy in critically ill patients.

Accurate Characterization of Extravascular Lung Water in Acute Respiratory Distress Syndrome

Critical Care Medicine. Jun, 2008  |  Pubmed ID: 18496374

Measurements of extravascular lung water (EVLW) correlate to the degree of pulmonary edema and have substantial prognostic information in critically ill patients. Prior studies using single indicator thermodilution have reported that 21% to 35% of patients with clinical acute respiratory distress syndrome (ARDS) have normal EVLW (<10 mL/kg). Given that lung size is independent of actual body weight, we sought to determine whether indexing EVLW to predicted or adjusted body weight affects the frequency of increased EVLW in patients with ARDS.

Toll-like Receptor 1 Polymorphisms Affect Innate Immune Responses and Outcomes in Sepsis

American Journal of Respiratory and Critical Care Medicine. Oct, 2008  |  Pubmed ID: 18635889

Polymorphisms affecting Toll-like receptor (TLR)-mediated responses could predispose to excessive inflammation during an infection and contribute to an increased risk for poor outcomes in patients with sepsis.

Pulmonary Vs Nonpulmonary Sepsis and Mortality in Acute Lung Injury

Chest. Sep, 2008  |  Pubmed ID: 18641112

Acute lung injury (ALI) is a frequent complication of sepsis. It is unclear if a pulmonary vs nonpulmonary source of sepsis affects mortality in patients with sepsis-induced ALI.

Biomarkers in Acute Lung Injury: Are We Making Progress?

Critical Care Medicine. Aug, 2008  |  Pubmed ID: 18664801

Direct Visualization of the Endomitotic Cell Cycle in Living Megakaryocytes: Differential Patterns in Low and High Ploidy Cells

Cell Cycle (Georgetown, Tex.). Aug, 2008  |  Pubmed ID: 18677109

Endomitosis in megakaryocytes (MKs) involves repeated DNA replication in the absence of cytokinesis and is a crucial part of MK development. However, chromosomal dynamics have never been observed in living MKs. We developed a new transgenic mouse model in which the expression of human histone H2B fused in-frame to green fluorescent protein is targeted to MKs. Ex vivo time-lapse microscopy analysis indicated that chromosomal condensation occurs at early mitosis in all MKs. In high ploidy MKs (>or=8N), late anaphase was marked by a ring-type alignment of chromosomes with multiple territories formed between them. By contrast, in low ploidy MKs mitotic chromosomes segregated to form two groups separated by a clear space before re-joining to one cluster. This is the first study to document chromosomal segregation patterns during endomitosis ex vivo and to indicate their potential differential regulation in low and high ploidy cells.

The Essential Nature of Healthcare Databases in Critical Care Medicine

Critical Care (London, England). 2008  |  Pubmed ID: 18771579

Medical databases serve a critical function in healthcare, including the areas of patient care, administration, research and education. The quality and breadth of information collected into existing databases varies tremendously, between databases, between institutions and between national boundaries. The field of critical care medicine could be advanced substantially by the development of comprehensive and accurate databases.

Racial and Ethnic Disparities in Mortality from Acute Lung Injury

Critical Care Medicine. Jan, 2009  |  Pubmed ID: 19050621

Little is known about the influence of race and ethnicity on mortality from acute lung injury (ALI). We sought to determine whether black race or Hispanic ethnicity is independently associated with mortality among patients with ALI.

Going Global with Sepsis: the Need for National Registries

Critical Care Medicine. Jan, 2009  |  Pubmed ID: 19112292

The Effect of Diabetes Mellitus on Organ Dysfunction with Sepsis: an Epidemiological Study

Critical Care (London, England). 2009  |  Pubmed ID: 19216780

Diabetes mellitus (DM) is one of the most common chronic co-morbid medical conditions in the USA and is frequently present in patients with sepsis. Previous studies reported that people with DM and severe sepsis are less likely to develop acute lung injury (ALI). We sought to determine whether organ dysfunction differed between people with and without DM and sepsis.

The Bioscience Revolution & the Biological Weapons Threat: Levers & Interventions

Globalization and Health. 2009  |  Pubmed ID: 19220910

In December 2008, the US Commission on the Prevention of Weapons of Mass Destruction Proliferation and Terrorism, released a report, World At Risk. The Report points to the fact that, not only is the use of a weapon of mass destruction in a terrorist attack before the end of 2013, more likely than not, but also to the fact that terrorists are more likely to be able to obtain and use biological weapons than nuclear. This paper examines the recommendations of the report in the context of the historic and geopolitical changes, in particular globalization. The authors highlight the "dual-use" dilemma, as described in the report, as the paradoxical use of technology developed for the benefit of mankind being used for sinister purposes. The mitigation of such a threat lies in broad stakeholder involvement and cooperation, including non-state actors, governments and the bio-tech industry itself. The importance of vigilance measures within the life science community is emphasized and, the authors propose, could include a web-based didactic course in bioterrorism and weapons of mass destruction identification. The site could outline safety protocols, have detailed disaster management tutorials, and could be specifically tailored for different subsets of industry and health professionals. The paper concludes with an endorsement of a multi-pronged approach including strong international guidelines and intelligence cooperation and preparatory measures such as the wide-spread use of detection systems as well as diagnostic decision support systems for bioterrorism detection at the local level.

Extending International Sepsis Epidemiology: the Impact of Organ Dysfunction

Critical Care (London, England). 2009  |  Pubmed ID: 19291262

In the previous issue of Critical Care, Blanco and colleagues contributed to a growing body of literature on the international epidemiology of severe sepsis. Taken together, these studies confirm that the sepsis incidence is high, that the development of organ dysfunction is a major determinant of mortality and that the occurrence of organ dysfunction is influenced by chronic comorbid medical conditions. It is clear that early detection of organ dysfunction and serial sequential organ dysfunction scoring provides us with the best chance to optimize clinical care. Identifying factors that contribute to the development of organ dysfunction in sepsis will lead to the development of new treatment modalities that will reduce mortality. Future studies must therefore focus on the impact of new treatment modalities for preventing progression to multiple organ dysfunction syndrome and consequent mortality in sepsis.

Extravascular Lung Water Measurement in Acute Respiratory Distress Syndrome

Critical Care Medicine. Jan, 2009  |  Pubmed ID: 19318817

Recent Trends in Acute Lung Injury Mortality: 1996-2005

Critical Care Medicine. May, 2009  |  Pubmed ID: 19325464

Studies from single centers have suggested that mortality from acute lung injury (ALI) has declined over time. However, recent trends in ALI mortality from centers across the United States are unknown. We sought to determine whether recent advances in the treatment of ALI and related critical illnesses have resulted in decreased mortality from ALI.

The International PROGRESS Registry of Patients with Severe Sepsis: Drotrecogin Alfa (activated) Use and Patient Outcomes

Critical Care (London, England). 2009  |  Pubmed ID: 19566927

Since the launch of drotrecogin alfa activated (DrotAA), institutions and individual countries have published data on its use in clinical practice, based on audit or registry data. These studies were limited in size and geographic locale and included patients with greater disease severity and higher mortality than those in clinical trials. The purpose of this study was to compare baseline characteristics and clinical outcomes (using appropriate statistical adjustments) of patients treated or not treated with DrotAA from the international PROGRESS (Promoting Global Research Excellence in Severe Sepsis) cohort study of severe sepsis.

Alcohol Abuse Enhances Pulmonary Edema in Acute Respiratory Distress Syndrome

Alcoholism, Clinical and Experimental Research. Oct, 2009  |  Pubmed ID: 19572988

Pulmonary edema is a cardinal feature of the life-threatening condition known as acute respiratory distress syndrome (ARDS). Patients with chronic alcohol abuse are known to be at increased risk of developing and dying from ARDS. Based upon preclinical data, we hypothesized that a history of chronic alcohol abuse in ARDS patients is associated with greater quantities and slower resolution of pulmonary edema compared with ARDS patients without a history of alcohol abuse.

Global Health: Where Are Our Priorities?

British Medical Bulletin. 2009  |  Pubmed ID: 19625368

The subject of 'global health' can be considered from multiple points of view. While epidemiologists might describe global health problems in categories of pathology groups, social scientists might consider the problem from the stand point of institutional and infrastructural strengths and failings. An over-arching theme, however, is that the distribution of the burden of ill health is disproportionately carried by the poor. This paper aims to defend the idea that inequality should be considered the main priority in global ill health.

Adult Mice Generated from Induced Pluripotent Stem Cells

Nature. Sep, 2009  |  Pubmed ID: 19672243

Recent landmark experiments have shown that transient overexpression of a small number of transcription factors can reprogram differentiated cells into induced pluripotent stem (iPS) cells that resemble embryonic stem (ES) cells. These iPS cells hold great promise for medicine because they have the potential to generate patient-specific cell types for cell replacement therapy and produce in vitro models of disease, without requiring embryonic tissues or oocytes. Although current iPS cell lines resemble ES cells, they have not passed the most stringent test of pluripotency by generating full-term or adult mice in tetraploid complementation assays, raising questions as to whether they are sufficiently potent to generate all of the cell types in an organism. Whether this difference between iPS and ES cells reflects intrinsic limitations of direct reprogramming is not known. Here we report fertile adult mice derived entirely from iPS cells that we generated by inducible genetic reprogramming of mouse embryonic fibroblasts. Producing adult mice derived entirely from a reprogrammed fibroblast shows that all features of a differentiated cell can be restored to an embryonic level of pluripotency without exposure to unknown ooplasmic factors. Comparing these fully pluripotent iPS cell lines to less developmentally potent lines may reveal molecular markers of different pluripotent states. Furthermore, mice derived entirely from iPS cells will provide a new resource to assess the functional and genomic stability of cells and tissues derived from iPS cells, which is important to validate their utility in cell replacement therapy and research applications.

Acinetobacter Lwoffii: Bacteremia Associated with Acute Gastroenteritis

Travel Medicine and Infectious Disease. Sep, 2009  |  Pubmed ID: 19747669

Acinetobacter lwoffii is a non-fermentative aerobic gram-negative bacillus that is seen as a normal flora of the oropharynx and skin in approximately 25% of the healthy individuals. Due to its ubiquitous nature, it is a potential opportunistic pathogen in patients with impaired immune systems, and it has been identified as a cause of nosocomial infections like septicemia, pneumonia, meningitis, urinary tract infections, skin and wound infections. To our knowledge, this is the first case reported of a community acquired A. lwoffii bacteremia associated with gastroenteritis.

Enhancing Global Control of Alcohol to Reduce Unsafe Sex and HIV in Sub-Saharan Africa

Globalization and Health. 2009  |  Pubmed ID: 19919703

Sub-Saharan Africa carries a massive dual burden of HIV and alcohol disease, and these pandemics are inextricably linked. Physiological and behavioural research indicates that alcohol independently affects decision-making concerning sex, and skills for negotiating condoms and their correct use. More than 20 studies in Africa have reported higher occurrence of HIV among people with problem drinking; a finding strongly consistent across studies and similar among women and men. Conflation of HIV and alcohol disease in these setting is not surprising given patterns of heavy-episodic drinking and that drinking contexts are often coterminous with opportunities for sexual encounters. HIV and alcohol also share common ground with sexual violence. Both perpetrators and victims of sexual violence have a high likelihood of having drunk alcohol prior to the incident, as with most forms of violence and injury in sub-Saharan Africa. Reducing alcohol harms necessitates multi-level interventions and should be considered a key component of structural interventions to alleviate the burden of HIV and sexual violence. Brief interventions for people with problem drinking (an important component of primary health care), must incorporate specific discussion of links between alcohol and unsafe sex, and consequences thereof. Interventions to reduce alcohol harm among HIV-infected persons are also an important element in positive-prevention initiatives. Most importantly, implementation of known effective interventions could alleviate a large portion of the alcohol-attributable burden of disease, including its effects on unsafe sex, unintended pregnancy and HIV transmission.

The CMO and the Medical Management of Inpatient Care

Hospitals & Health Networks / AHA. Oct, 2009  |  Pubmed ID: 19960815

Fluid Balance and Colloid Osmotic Pressure in Acute Respiratory Failure: Optimizing Therapy

Expert Review of Respiratory Medicine. Dec, 2009  |  Pubmed ID: 20477354

Acute lung injury and acute respiratory distress syndrome continue to be major causes of morbidity and mortality in the intensive care unit due to a lack of specific effective therapy. Affecting nearly 200,000 people every year in the USA alone, patients with this syndrome often require extensive intensive care unit and hospital care, leading to enormous utilization of healthcare resources and significant expenditures, and ultimately leaving survivors with a reduced quality of life. A disease of altered capillary permeability, acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is characterized by significant fluid imbalances and oncotic pressure changes. Although investigations directed at these abnormalities may improve patient-centered outcomes, fluid management in ALI/ARDS continues to be a source of great controversy. In this review, we discuss fluid balance and the colloid osmotic pressure gradients in ALI/ARDS, followed by a review of the prognostic implications of increasing extravascular lung water, and conclude with contemporary approaches to optimizing therapy in this condition, including the role of albumin and diuretic therapy.

Global Utilization of Low-dose Corticosteroids in Severe Sepsis and Septic Shock: a Report from the PROGRESS Registry

Critical Care (London, England). 2010  |  Pubmed ID: 20525247

The benefits and use of low-dose corticosteroids (LDCs) in severe sepsis and septic shock remain controversial. Surviving sepsis campaign guidelines suggest LDC use for septic shock patients poorly responsive to fluid resuscitation and vasopressor therapy. Their use is suspected to be wide-spread, but paucity of data regarding global practice exists. The purpose of this study was to compare baseline characteristics and clinical outcomes of patients treated or not treated with LDC from the international PROGRESS (PROmoting Global Research Excellence in Severe Sepsis) cohort study of severe sepsis.

Novel Findings from the Second Wave of Adult PH1N1 in the United States

Critical Care Medicine. Oct, 2010  |  Pubmed ID: 20625279

To describe the impact of novel pH1N1 virus in Atlanta, GA, for inpatient and intensive care services, including lung lavage data and determinants of disease outcome, from the earliest group of infected US population after initial cases.

Critical Care Trial Design and Interpretation: a Primer

Critical Care Medicine. Sep, 2010  |  Pubmed ID: 20639755

Better understanding of the pathophysiology of critical illness has led to an increase in clinical trials designed to improve the clinical care and outcomes of patients with life-threatening illness. Knowledge of basic principles of clinical trial design and interpretation will assist the clinician in better applying the results of these studies into clinical practice.

Stem Cells in Sepsis and Acute Lung Injury

Critical Care Medicine. Dec, 2010  |  Pubmed ID: 20838330

Sepsis and acute lung injury continue to be major causes of morbidity and mortality worldwide despite advances in our understanding of pathophysiology and the discovery of new management strategies. Recent investigations show that stem cells may be beneficial as prognostic biomarkers and novel therapeutic strategies in these syndromes. This article reviews the potential use of endogenous adult tissue-derived stem cells in sepsis and acute lung injury as prognostic markers and also as exogenous cell-based therapy.

Rational or Rationalized Choices in Fluid Resuscitation?

Critical Care (London, England). 2010  |  Pubmed ID: 21092151

The war between colloids and crystalloids wages on. In a large multinational survey of fluid prescribing practices in critically ill patients, we have a new and intriguing snapshot of global fluid resuscitation practices. Colloids are more often used for impaired perfusion or low cardiac output, and the choice of colloid or crystalloid varies enormously between countries. Why are some ICUs prescribing colloids more often than crystalloids when there is little convincing evidence that colloids are superior for fluid resuscitation? Are colloids advantageous in certain diseases, or in specific regional patient populations that have not yet been elucidated? Perhaps we should look inwards: the answer may not be more randomized clinical trials, but better adherence to current guidelines and treatment recommendations.

Umbilical Venous Catheter Complication in an Infant with Left-sided Congenital Diaphragmatic Hernia: Extravasation Owing to Hepatic Vein Catheterization

Journal of Pediatric Surgery. Dec, 2010  |  Pubmed ID: 21129529

Infants with left-sided congenital diaphragmatic hernia (CDH) are subject to possible intrahepatic placement of the umbilical venous catheter (UVC) during catheterization. A left-sided CDH containing the left lobe of the liver is subject to repositioned anatomy of the umbilical vein, ductus venosus, and hepatic vasculature. This substantially increases the risk of incidentally cannulating the shifted intrahepatic vessels of the liver when placing a UVC. We present a case of hepatic extravasation with line erosion through the liver capsule secondary to UVC placement in an infant with left-sided CDH containing the left lobe of the liver. The patient underwent successful repair of the diaphragmatic defect and is a healthy youngster without complication from CDH or extravasation of the liver capsule. Cannulation of the hepatic vasculature cannot be ruled out with radiograph in infants with left-sided CDH.

Marital Status and the Epidemiology and Outcomes of Sepsis

Chest. Jun, 2010  |  Pubmed ID: 20173054

Sepsis is a major public health problem. Social factors may affect health behaviors, economic resources, and immune response, leading to hospitalization for infection. This study examines the association between marital status and sepsis incidence and outcomes in a population-based cohort.

Development of a Short Cannabis Problems Questionnaire for Adolescents in the Community

Addictive Behaviors. Jul, 2010  |  Pubmed ID: 20356683

The widespread and harmful use of cannabis amongst young people in the community has been well established. In order to assist in identifying young people at risk of harm for their cannabis use, the present paper documents the development of a short 12-item cannabis problems measure--the Cannabis Problems Questionnaire for Adolescents, Short form (CPQ-A-S). The CPQ-A-S was derived from the 27-item Cannabis Problems Questionnaire for Adolescents (CPQ-A) which had been shown in an earlier study to be a reliable and valid indicator of cannabis problems in adolescents. Tetrachoric correlations amongst items were examined and the more redundant items removed. Psychometrics of the shorter scale were then evaluated through factor analysis, and logistic regression used to demonstrate scale validity. This is the first short scale of cannabis problems derived for adolescents and it should prove a useful tool in both research and community applications.

Role of Black Carbon in the Distribution of Polychlorinated Dibenzo-p-dioxins/dibenzofurans in Aged Field-contaminated Soils

Chemosphere. Jan, 2011  |  Pubmed ID: 21130485

Floodplain soils containing elevated levels of polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs) were collected from several locations along the Tittabawassee River (Michigan, USA). The PCDD/F profiles of these soils exhibited distinct congener patterns consistent with byproducts from either chloralkali manufacturing or chlorophenols productions. Black carbon (BC) particles were isolated for the first time from floodplain soil impacted by PCDD/Fs. Petrographic analysis showed that BC particles, including coal, oxidized coal, metallurgical coke, depositional carbon, coal tar/pitch, cenosphere, and charcoal, comprised approximately 30% by volume of the organic fraction with size range of 250μm-2000μm from a typical floodplain soil. The BC particles with anthropogenic origin such as pitch and coke associated with the chloralkali production process served as both the source and subsequent transporter for the highly hydrophobic PCDD/Fs. These anthropogenic BC particles were enriched with high levels of PCDFs, containing approximately 1000-fold the concentration found in the bulk soil. The strong association of PCDD/Fs with anthropogenic BC directly impacts the physicochemical and biological availability thus the risk associated with these hydrophobic organochlorines in soils and sediments.

Does Albumin Fluid Resuscitation in Sepsis Save Lives?

Critical Care Medicine. Feb, 2011  |  Pubmed ID: 21248532

Barriers and Facilitators to Cannabis Treatment

Drug and Alcohol Review. Apr, 2011  |  Pubmed ID: 21521384

Introduction and Aims. Despite its continued widespread use, relatively few individuals with cannabis use disorders present to treatment services. There is a dearth of research examining the reasons for this observed underutilisation of treatment. The aim of this paper is to examine barriers and facilitators to entry into cannabis treatment. Design and Methods. Three surveys of regular cannabis users in treatment (n = 100), in the community (n = 100) and from a widespread Internet sample (n = 294). Results. Perceived barriers included: not being aware of treatment options; thinking treatment is unnecessary; not wanting to stop using cannabis; and wanting to avoid the stigma associated with accessing treatment. Perceived facilitators included: improving available information on treatment; keeping treatment specific to cannabis; offering additional services, such as telephone support; and simplifying treatment admission processes. Discussion and Conclusions. Participant's perceptions differed significantly depending on their age, gender and treatment status. Participants in treatment typically reported barriers intrinsic to the individual while participants from the community reported barriers relating to the treatment available. Reported facilitators were more homogenous and most commonly related to availability of information. [Gates P, Copeland J, Swift W, Martin G. Barriers and facilitators to cannabis treatment. Drug Alcohol Rev 2011].

Metabolic Effects of Albumin Therapy in Acute Lung Injury Measured by Proton Nuclear Magnetic Resonance Spectroscopy of Plasma: a Pilot Study

Critical Care Medicine. Oct, 2011  |  Pubmed ID: 21705902

Improved means to monitor and guide interventions could be useful in the intensive care unit. Metabolomic analysis with bioinformatics is used to understand mechanisms and identify biomarkers of disease development and progression. This pilot study evaluated plasma proton nuclear magnetic resonance spectroscopy as a means to monitor metabolism following albumin administration in acute lung injury patients.

Clinical Review: Update on Hemodynamic Monitoring--a Consensus of 16

Critical Care (London, England). 2011  |  Pubmed ID: 21884645

Hemodynamic monitoring plays a fundamental role in the management of acutely ill patients. With increased concerns about the use of invasive techniques, notably the pulmonary artery catheter, to measure cardiac output, recent years have seen an influx of new, less-invasive means of measuring hemodynamic variables, leaving the clinician somewhat bewildered as to which technique, if any, is best and which he/she should use. In this consensus paper, we try to provide some clarification, offering an objective review of the available monitoring systems, including their specific advantages and limitations, and highlighting some key principles underlying hemodynamic monitoring in critically ill patients.

Clinical Trials: Innovation, Progress and Controversy

Open Access Journal of Clinical Trials. Aug, 2011  |  Pubmed ID: 21921992

Stem Cells in Sepsis and Acute Lung Injury

The American Journal of the Medical Sciences. Apr, 2011  |  Pubmed ID: 20890174

Critical illnesses continue to be major causes of morbidity and mortality worldwide. Recent investigations show that stem cells may be beneficial as prognostic biomarkers and novel therapeutic strategies in these syndromes. This article reviews the use of stem cells in sepsis and acute lung injury as prognostic biomarkers and also as a potential for exogenous cell-based therapy.

Protocols in the Management of Critical Illness

Critical Care (London, England). Mar, 2011  |  Pubmed ID: 22424130

Care of the critically ill patient is becoming increasingly complex. Protocols, which standardize care of patients with similar diseases, represent a potential solution to managing multiple simultaneous problems in critically ill patients. In this article, we examine the advantages and disadvantages to care protocolization, and posit that careful and thoughtful implementation of protocols is likely to benefit patients. We also discuss the potential for unintended consequences, and even harm, with protocolization in critically ill patients using the Critical Illness Outcomes Study as a model to examine the effects of protocolization in large populations of intensive care patients.

Short Women with Severe Sepsis-related Acute Lung Injury Receive Lung Protective Ventilation Less Frequently: an Observational Cohort Study

Critical Care (London, England). Nov, 2011  |  Pubmed ID: 22044724

ABSTRACT: INTRODUCTION: Lung protective ventilation (LPV) has been shown to improve survival and the duration of mechanical ventilation in acute lung injury (ALI) patients. Mortality of ALI may vary by gender, which could result from treatment variability. Whether gender is associated with the use of LPV is not known. METHODS: A total of 421 severe sepsis-related ALI subjects in the Consortium to Evaluate Lung Edema Genetics from seven teaching hospitals between 2002 and 2008 were included in our study. We evaluated patients' tidal volume, plateau pressure and arterial pH to determine whether patients received LPV during the first two days after developing ALI. The odds ratio of receiving LPV was estimated by a logistic regression model with robust and cluster options. RESULTS: Women had similar characteristics as men with the exception of lower height and higher illness severity, as measured by Acute Physiology and Chronic Health Evaluation (APACHE) II score. 225 (53%) of the subjects received LPV during the first two days after ALI onset; women received LPV less frequently than men (46% versus 59%, P < 0.001). However, after adjustment for height and severity of illness (APACHE II), there was no difference in exposure to LPV between men and women (P = 0.262). CONCLUSIONS: Short people are less likely to receive LPV, which seems to explain the tendency of clinicians to adhere to LPV less strictly in women. Strategies to standardize application of LPV, independent of differences in height and severity of illness, are necessary.

The Impact of Cormorbid Conditions on Critical Illness

Critical Care Medicine. Dec, 2011  |  Pubmed ID: 22094497

To review the current knowledge of common comorbidities in the intensive care unit, including diabetes mellitus, chronic obstructive pulmonary disease, cancer, end-stage renal disease, end-stage liver disease, HIV infection, and obesity, with specific attention to epidemiology, contribution to diseases and outcomes, and the impact on treatments in these patients.

Effectiveness of Activated Carbon and Biochar in Reducing the Availability of Polychlorinated Dibenzo-p-dioxins/Dibenzofurans in Soils

Environmental Science & Technology. Jan, 2012  |  Pubmed ID: 22136630

Five activated carbons (ACs) and two biochars were tested as amendments to reduce the availability of aged polychlorinated dibenzo-p-dioxin/dibenzofurans (PCDD/Fs) in two soils. All sorbents (ACs and biochars) tested substantially reduced the availability of PCDD/Fs measured by polyoxymethylene (POM) passive uptake and earthworm (E. fetida) biouptake. Seven sorbents amended at a level of 0.2 × soil total organic carbon (0.2X) reduced the passive uptake (physicochemical availability) of total PCDD/Fs in POM by 40% to 92% (or toxic equivalent by 48% to 99%). Sorbents with finer particle sizes or more macropores showed higher reduction efficiencies. The powdered regenerated AC and powdered coconut AC demonstrated to be the most effective and the two biochars also performed reasonably well especially in the powdered form. The passive uptake of PCDD/F in POM increased approximately 4 to 5 fold as the contact time between POM and soil slurry increased from 24 to 120 d while the efficacy of ACs in reducing the physicochemical availability remained unchanged. The reduction efficiencies measured by POM passive uptake for the regenerated AC were comparable to those measured by earthworm biouptake (bioavailability) at both dose levels of 0.2X and 0.5X. The biota-soil accumulation factor (BSAF) values for unamended soil ranged from 0.1 for tetra-CDD/F to 0.02 for octa-CDD/F. At both dose levels, the regenerated AC reduced the BSAFs to below 0.03 with the exception of two hexa-CDD/Fs. The reduction efficiencies measured by earthworm for coconut AC and corn stover biochar were generally less than those measured by POM probably due to larger particle sizes of these sorbents that could not be ingested by the worms.

Loss of Liver Fatty Acid Binding Protein Significantly Alters Hepatocyte Plasma Membrane Microdomains

Journal of Lipid Research. Jan, 2012  |  Pubmed ID: 22223861

While lipid-rich microdomains of hepatocyte plasma membranes serve as the major scaffolding regions for cholesterol transport proteins important in cholesterol disposition, little is known regarding intracellular factors regulating cholesterol distribution therein. Based on its ability to bind cholesterol and alter hepatic cholesterol accumulation, the cytosolic liver type fatty acid binding protein (L-FABP) was hypothesized as a candidate protein regulating these microdomains. Compared to wild-type hepatocyte plasma membranes, L-FABP gene ablation significantly increased the proportion of cholesterol-rich microdomains. Lack of L-FABP selectively increased cholesterol, phospholipid (esp. phosphatidylcholine), and branched-chain fatty acid accumulation in the cholesterol-rich microdomains. These cholesterol-rich microdomains are important due to enrichment therein of significant amounts of key transport proteins involved in uptake of: i) cholesterol (SR-B1, ABCA-1, P-gp, SCP-2); ii) fatty acid (FATP); and iii) glucose (GLUT2, GLUT1, insulin receptor). L-FABP gene ablation enhanced the concentration of SCP-2, SR-B1, FATP4, and GLUT1 in the cholesterol-poor microdomains, with functional implications in HDL-mediated uptake and efflux of cholesterol. Thus L-FABP gene ablation significantly impacted the proportion of cholesterol-rich versus poor microdomains in the hepatocyte plasma membrane and altered the distribution of lipids and proteins involved in cholesterol uptake therein.

Circulating Endothelial Progenitor Cells Inversely Associate with Organ Dysfunction in Sepsis

Intensive Care Medicine. Feb, 2012  |  Pubmed ID: 22331369

PURPOSE: Endothelial dysfunction is a primary contributor to sepsis-related organ dysfunction and death. In sepsis animal models, endothelial progenitor cells (EPC) have contributed to vascular repair. The role of endothelial progenitor cells as a biomarker for organ dysfunction is still unknown. We hypothesized that circulating numbers of endothelial progenitor cells would be associated with improved outcomes in sepsis. METHODS: Prospective, observational single-center cohort study in adult intensive care units at Grady Memorial Hospital, an affiliate of Emory University, from July 2007 through April 2009. Peripheral blood was obtained from 95 patients with sepsis, 37 intensive care unit controls, and 51 healthy controls, of whom only 86 patients with sepsis were used in the analysis because we were not able to obtain enough blood in 9 sepsis patients. Clinical data were obtained, and organ dysfunction was measured by Sepsis-Related Organ Failure Assessment (SOFA) score. Endothelial progenitor cells were assessed by a colony-forming unit (CFU) assay in which peripheral blood mononuclear cells were isolated using Ficoll density-gradient centrifugation and cultured in growth media. RESULTS: The patients with sepsis had significantly lower mean endothelial progenitor cell colony counts compared with intensive care unit controls (p = 0.035) and healthy controls (p = 0.0005). There was no difference in colony counts between ICU controls and healthy controls (p = 0.81). In the sepsis patients, EPC CFU numbers inversely associated with SOFA score, adjusting for mortality (r (2) = 0.05, p = 0.04). CONCLUSION: Increased circulating endothelial progenitor cells inversely correlate with organ dysfunction in sepsis patients.

Approaching Sepsis Solutions Using the National Institutes of Health Roadmap*

Critical Care Medicine. Mar, 2012  |  Pubmed ID: 22343857

Investigating Differential Binding of Polychlorinated Dibenzo-p-dioxins/dibenzofurans in Soil and Soil Components Using Selective Supercritical Fluid Extraction

Chemosphere. Jul, 2012  |  Pubmed ID: 22406311

Supercritical fluid extraction (SFE) with pure carbon dioxide was performed at increasingly strong conditions to investigate differential binding of polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs) in two impacted soils, in their sieved size fractions, and in small (a few mg) samples of industry-related waste products separated from impacted soil. The binding strengths of PCDD/Fs were shown to be different in the two soils, and in their different soil particle size fractions. As might be expected based on surface area considerations, one soil showed the strongest binding in the smallest (<5μm) sieved fraction. However, the other soil showed the strongest binding in the larger sized fractions, possibly indicating that process-related particles could be controlling PCDD/F binding. Selective SFE of various types of particles including black carbon and charcoal (separated from soil), and from a suspected process anode residue did show different PCDD/F binding behavior ranging from quite weak binding (charcoal) to very strong binding (anode particles). Shifts to the stronger SFE fractions in the soils after activated carbon treatment agreed well with the decreases previously found in the uptake of PCDD/Fs by earthworms, as well as decreases in their freely-dissolved aqueous concentrations in soil/water slurries. These results show that, as previously demonstrated for PAHs and PCBs, selective SFE can be a useful tool to investigate differences in PCDD/F binding behaviors in impacted soils and sediments and their component parts, as well as a rapid tool for estimating the effectiveness of activated carbon treatments on decreasing the bioavailability of PCDD/Fs in soils and sediments.

Global Health Funding and Economic Development

Globalization and Health. 2012  |  Pubmed ID: 22490207

The impact of increased national wealth, as measured by Gross Domestic Product (GDP), on public health is widely understood, however an equally important but less well-acclaimed relationship exists between improvements in health and the growth of an economy. Communicable diseases such as HIV, TB, Malaria and the Neglected Tropical Diseases (NTDs) are impacting many of the world's poorest and most vulnerable populations, and depressing economic development. Sickness and disease has decreased the size and capabilities of the workforce through impeding access to education and suppressing foreign direct investment (FDI). There is clear evidence that by investing in health improvements a significant increase in GDP per capita can be attained in four ways: Firstly, healthier populations are more economically productive; secondly, proactive healthcare leads to decrease in many of the additive healthcare costs associated with lack of care (treating opportunistic infections in the case of HIV for example); thirdly, improved health represents a real economic and developmental outcome in-and-of itself and finally, healthcare spending capitalises on the Keynesian 'economic multiplier' effect. Continued under-investment in health and health systems represent an important threat to our future global prosperity. This editorial calls for a recognition of health as a major engine of economic growth and for commensurate investment in public health, particularly in poor countries.

Trends in the Incidence of Noncardiogenic Acute Respiratory Failure: the Role of Race

Critical Care Medicine. May, 2012  |  Pubmed ID: 22511134

We sought to examine trends in the race-specific incidence of acute respiratory failure in the United States.

Clinical Review: Respiratory Monitoring in the ICU - a Consensus of 16

Critical Care (London, England). 2012  |  Pubmed ID: 22546221

Monitoring plays an important role in the current management of patients with acute respiratory failure but sometimes lacks definition regarding which 'signals' and 'derived variables' should be prioritized as well as specifics related to timing (continuous versus intermittent) and modality (static versus dynamic). Many new techniques of respiratory monitoring have been made available for clinical use recently, but their place is not always well defined. Appropriate use of available monitoring techniques and correct interpretation of the data provided can help improve our understanding of the disease processes involved and the effects of clinical interventions. In this consensus paper, we provide an overview of the important parameters that can and should be monitored in the critically ill patient with respiratory failure and discuss how the data provided can impact on clinical management.

Sepsis, Severe Sepsis and Septic Shock: Changes in Incidence, Pathogens and Outcomes

Expert Review of Anti-infective Therapy. Jun, 2012  |  Pubmed ID: 22734959

Sepsis has been around since the dawn of time, having been described for more than 2000 years, although clinical definitions are recent. The consensus sepsis definitions have permitted worldwide epidemiological studies of sepsis to be conducted. We now recognize the common nature of sepsis and the consistency of its disease - particularly severe sepsis and septic shock. The incidence of sepsis, severe sepsis and septic shock continues to increase, and although Gram-positive bacterial pathogens remain the most common cause of sepsis, fungal organisms are increasing rapidly. We have made progress over the past half-century in identifying and treating patients with sepsis, and decreasing fatality rates reflect this progress. However, owing to the increasing incidence of sepsis, the number of people who die each year continues to increase. The mortality with sepsis, particularly related to treating organ dysfunction, remains a priority to clinicians worldwide and is deserving of greater public health attention.

Vitamin D in Sepsis: from Basic Science to Clinical Impact

Critical Care (London, England). Jul, 2012  |  Pubmed ID: 22809263

ABSTRACT: The growing basic and clinical investigations into the extraskeletal effects of vitamin D have revealed roles in the functioning of the immune system, generating interesting questions about this nutrient's connections to sepsis. This article briefly reviews the current science of the function of vitamin D in the immune system as well as the emerging clinical literature regarding its associations with respiratory infections, sepsis, and critical illness. Finally, we offer views on the potential future directions for research in the field by outlining potential relevant scenarios and outcomes.

AIDS: Ushering in a New Era of Shared Responsibility for Global Health

Globalization and Health. 2012  |  Pubmed ID: 22809397

ABSTRACT: For the first time since AIDS erupted as worldwide emergency, global leaders, the scientific community, activists and people living with HIV are venturing to speak about the end to the pandemic. Signs of hope abound: over 8 million people are receiving life-saving treatment, the number of new infections is on significant decline, the remarkable evidence of treatment's impact on preventing new infections and the aspiration of zero new HIV infections among children is firmly within grasp. This progress, won by people living with HIV and countries with support from partners such as the US programme PEPFAR, the Clinton Health Access Initiative and untold more, embodies global solidarity to bring about an AIDS-free generation. Shared responsibility and global solidarity represents a normative ideal to which both individual stakeholders and the global community must subscribe and embrace if our collective vision of an AIDS-free world is to be realised. The idea of shared responsibility and global solidarity needs to goes further than raising and investing resources and extend to the level of control countries take of their AIDS response. This editorial explores five areas that require further attention.

Aiming for a Negative Fluid Balance in Patients with Acute Lung Injury and Increased Intra-abdominal Pressure: a Pilot Study Looking at the Effects of PAL-treatment

Annals of Intensive Care. Jul, 2012  |  Pubmed ID: 22873416

Achievement of a negative fluid balance in patients with capillary leak is associated with improved outcome. We investigated the effects of a multi-modal restrictive fluid strategy aiming for negative fluid balance in patients with acute lung injury (ALI).

Vitamin D and Sepsis: An Emerging Relationship

Dermato-endocrinology. Apr, 2012  |  Pubmed ID: 22928065

Vitamin D insufficiency and sepsis are both highly prevalent worldwide problems and this article reviews the emerging science that is defining the intersections of these conditions. The importance of vitamin D's role in skeletal health has long been understood but recent evidence is beginning to highlight its role in the functioning of other physiologic systems of the body. Basic science data reveal its integral role in local immune responses to pathogens and the systemic inflammatory pathways of sepsis. Furthermore, clinical scientists have found associations with respiratory infections, critical illness and sepsis but the causal relationship and its clinical impact have yet to be clearly defined. The article ends with speculations on the connections between racial disparities and seasonal differences in sepsis and vitamin D insufficiency.

Potential for Overuse of Corticosteroids and Vasopressin in Septic Shock

Critical Care (London, England). Sep, 2012  |  Pubmed ID: 23102413

Outcomes for Critically Ill Patients with HIV and Severe Sepsis in the Era of Highly Active Antiretroviral Therapy

Journal of Critical Care. Feb, 2012  |  Pubmed ID: 22033058

With the advent of highly active antiretroviral therapy (HAART), sepsis has become a more frequent ICU diagnosis for patients with HIV infections. Yet, little is known about the etiologies of acute infections in critically ill patients with HIV and the factors that affect in-hospital mortality.