Association of histological chorioamnionitis and magnesium sulfate treatment in singleton and dichorionic twin pregnancies with preterm premature rupture of membranes: preliminary observations.

Objective To evaluate the possible association between antenatal magnesium sulfate treatment with histological chorioamnionitis in patients with singleton or dichorionic twins that had preterm premature rupture of the membranes. Methods This was an observational study performed in patients admitted to the hospital with rupture of membranes before 34 weeks' gestation. The primary outcome was histological chorioamnionitis and the primary predictor was antenatal magnesium sulfate treatment. A logistic regression model was used without consideration of other antenatal medical treatments. Results Among 107 patients with preterm deliveries, 57 were admitted to the hospital before 34 weeks' gestation with preterm premature rupture of membranes. Fifty-cases were excluded from the analysis because they were admitted after 34 weeks' gestation, delivered before 24 weeks' gestation or had intrauterine fetal demise or monochorionic twins. The logistic regression analysis adjusting for maternal age, gravidity, parity, multiple gestation, gestational age at delivery, and birthweight, indicated that patients with singleton pregnancies and histological chorioamnionitis had received magnesium sulfate antenatally more frequently (χ2=6.46; P=0.01). The association between histological chorioamnionitis and magnesium sulfate treatment was not found among patients with dichorionic twin pregnancies with one intact gestational sac. Conclusions In this cohort of patients with preterm premature rupture of membranes admitted to the hospital before 34 week's gestation, those with singleton pregnancies treated antenatally with magnesium sulfate for neonatal neuroprotection had a greater rate of histological chorioamnionitis.

Obesity and 1-year outcomes in older Americans with severe sepsis.

OBJECTIVES: Although critical care physicians view obesity as an independent poor prognostic marker, growing evidence suggests that obesity is, instead, associated with improved mortality following ICU admission. However, this prior empirical work may be biased by preferential admission of obese patients to ICUs, and little is known about other patient-centered outcomes following critical illness. We sought to determine whether 1-year mortality, healthcare utilization, and functional outcomes following a severe sepsis hospitalization differ by body mass index. DESIGN: Observational cohort study. SETTING: U.S. hospitals. PATIENTS: We analyzed 1,404 severe sepsis hospitalizations (1999-2005) among Medicare beneficiaries enrolled in the nationally representative Health and Retirement Study, of which 597 (42.5%) were normal weight, 473 (33.7%) were overweight, and 334 (23.8%) were obese or severely obese, as assessed at their survey prior to acute illness. Underweight patients were excluded a priori. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Using Medicare claims, we identified severe sepsis hospitalizations and measured inpatient healthcare facility use and calculated total and itemized Medicare spending in the year following hospital discharge. Using the National Death Index, we determined mortality. We ascertained pre- and postmorbid functional status from survey data. Patients with greater body mass indexes experienced lower 1-year mortality compared with nonobese patients, and there was a dose-response relationship such that obese (odds ratio = 0.59; 95% CI, 0.39-0.88) and severely obese patients (odds ratio = 0.46; 95% CI, 0.26-0.80) had the lowest mortality. Total days in a healthcare facility and Medicare expenditures were greater for obese patients (p < 0.01 for both comparisons), but average daily utilization (p = 0.44) and Medicare spending were similar (p = 0.65) among normal, overweight, and obese survivors. Total function limitations following severe sepsis did not differ by body mass index category (p = 0.64). CONCLUSIONS: Obesity is associated with improved mortality among severe sepsis patients. Due to longer survival, obese sepsis survivors use more healthcare and result in higher Medicare spending in the year following hospitalization. Median daily healthcare utilization was similar across body mass index categories.

Extended-infusion cefepime reduces mortality in patients with Pseudomonas aeruginosa infections.

In an era of escalating resistance and a lack of new antimicrobial discovery, stewardship programs must utilize knowledge of pharmacodynamics to achieve maximal exposure in the treatment of Pseudomonas aeruginosa infections. We evaluated the clinical and economic outcomes associated with extended-infusion cefepime in the treatment of P. aeruginosa infections. This single-center study compared inpatients who received cefepime for bacteremia and/or pneumonia admitted from 1 January 2008 through 30 June 2010 (a 30-min infusion of 2 g every 8 h) to those admitted from 1 July 2010 through 31 May 2011 (a 4-h infusion of 2 g every 8 h). The overall mortality was significantly lower in the group that received extended-infusion treatment (20% versus 3%; P = 0.03). The mean length of stay was 3.5 days less for patients who received extended infusion (P = 0.36), and for patients admitted to the intensive care unit the mean length of stay was significantly less in the extended-infusion group (18.5 days versus 8 days; P = 0.04). Hospital costs were $23,183 less per patient, favoring the extended-infusion treatment group (P = 0.13). We conclude that extended-infusion treatment with cefepime provides increased clinical and economic benefits in the treatment of invasive P. aeruginosa infections.

Factors associated with elevated plateau pressure in patients with acute lung injury receiving lower tidal volume ventilation.

OBJECTIVES: Lung-protective ventilation with lower tidal volume and lower plateau pressure improves mortality in patients with acute lung injury and acute respiratory distress syndrome. We sought to determine the incidence of elevated plateau pressure in acute lung injury /acute respiratory distress syndrome patients receiving lower tidal volume ventilation and to determine the factors that predict elevated plateau pressure in these patients. PATIENTS: We used data from 1398 participants in Acute Respiratory Distress Syndrome Network trials, who received lower tidal volume ventilation (≤ 6.5mL/kg predicted body weight). DESIGN: We considered patients with a plateau pressure greater than 30cm H2O and/or a tidal volume less than 5.5mL/kg predicted body weight on study day 1 to have "elevated plateau pressure." We used logistic regression to identify baseline clinical variables associated with elevated plateau pressure and to develop a model to predict elevated plateau pressure using a subset of 1,188 patients. We validated the model in the 210 patients not used for model development. SETTING: Medical centers participating in Acute Respiratory Distress Syndrome Network clinical trials. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 1,398 patients in our study, 288 (20.6%) had elevated plateau pressure on day 1. Severity of illness indices and demographic factors (younger age, greater body mass index, and non-white race) were independently associated with elevated plateau pressure. The multivariable logistic regression model for predicting elevated plateau pressure had an area under the receiving operator characteristic curve of 0.71 for both the developmental and the validation subsets. CONCLUSIONS: acute lung injury patients receiving lower tidal volume ventilation often have a plateau pressure that exceeds Acute Respiratory Distress Syndrome Network goals. Race, body mass index, and severity of lung injury are each independently associated with elevated plateau pressure. Selecting a smaller initial tidal volume for non-white patients and patients with higher severity of illness may decrease the incidence of elevated plateau pressure. Prospective studies are needed to evaluate this approach.

Type 2 diabetes and 1-year mortality in intensive care unit patients.

BACKGROUND: Data on the prognostic impact of diabetes and diabetic complications in intensive care unit (ICU) patients are limited and inconsistent. We, therefore, examined mortality in ICU patients with type 2 diabetes with and without pre-existing heart and kidney diseases compared with nondiabetic patients. DESIGN: We conducted this population-based cohort study in Northern Denmark during 2005-2011. We included all ICU patients aged 40 years or older from the 17 ICUs in the area and identified type 2 diabetes by either a filled prescription for an antidiabetic drug, a previous diagnosis of diabetes, or an elevated glycosylated haemoglobin level. Diabetic patients were disaggregated according to pre-existing diagnoses of heart disease (myocardial infarction or heart failure) and kidney disease. We estimated 1-year mortality by the Kaplan-Meier method and hazard ratios of death (HRs) during follow-up using Cox regression, controlling for confounding factors and stratified by relevant subgroups. RESULTS: Among 45 018 ICU patients, 7219 (16·0%) had type 2 diabetes. Overall, 1-year mortality was 36·0% in ICU patients with type 2 diabetes, rising to 54·6% in patients with pre-existing heart and kidney diseases, compared with 29·1% in nondiabetic patients. Comparing diabetic with nondiabetic patients, the adjusted 0- to 30-day HR was 1·20 (95% confidence interval (CI): 1·13-1·26) and 1·19 (95% CI: 1·10-1·28) during the 31- to 365-day follow-up period. Pre-existing kidney disease further increased the impact of diabetes, while heart disease alone had no such effect. CONCLUSIONS: ICU patients with type 2 diabetes had higher 1-year mortality compared with nondiabetic ICU patients, particularly those with pre-existing kidney disease.

Preadmission metformin use and mortality among intensive care patients with diabetes: a cohort study.

INTRODUCTION: Metformin has anti-inflammatory and anti-thrombotic effects that may improve the outcome of critical illness, but clinical data are limited. We examined the impact of preadmission metformin use on mortality among intensive care unit (ICU) patients with type 2 diabetes. METHODS: We conducted this population-based cohort study among all persons admitted to the 17 ICUs in Northern Denmark (population approximately 1.8 million). We focused on all patients with type 2 diabetes who were admitted to the ICUs between January 2005 and December 2011. Through individual-level linkage of population-based medical databases, type 2 diabetes was identified using a previously validated algorithm including hospital diagnoses, filled prescriptions for anti-diabetic drugs, and elevated HbA1c levels. Metformin use was identified by filled prescriptions within 90 days before admission. Covariates included surgery, preadmission morbidity, diabetes duration, and concurrent drug use. We computed 30-day mortality and hazard ratios (HRs) of death using Cox regression adjusted for covariates, both overall and after propensity score matching. RESULTS: We included 7,404 adult type 2 diabetes patients, representing 14.0% of 52,964 adult patients admitted to the ICUs. Among type 2 diabetes patients, 1,073 (14.5%) filled a prescription for metformin as monotherapy within 90 days before admission and 1,335 (18.0%) received metformin in combination with other anti-diabetic drugs. Thirty-day mortality was 17.6% among metformin monotherapy users, 17.9% among metformin combination therapy users, and 25.0% among metformin non-users. The adjusted HRs were 0.80 (95% confidence interval (CI): 0.69, 0.94) for metformin monotherapy users and 0.83 (95% CI: 0.71, 0.95) for metformin combination therapy users, compared to non-users. Propensity-score-matched analyses yielded the same results. The association was evident across most subgroups of medical and surgical ICU patients, but most pronounced in elderly patients and in patients with well-controlled diabetes. Former metformin use was not associated with decreased mortality. CONCLUSIONS: Preadmission metformin use was associated with reduced 30-day mortality among medical and surgical intensive care patients with type 2 diabetes.

The association between body mass index, processes of care, and outcomes from mechanical ventilation: a prospective cohort study.

OBJECTIVE: To determine the association between excess weight and processes of care and outcomes for critically ill adults. DESIGN: Prospective cohort study. SETTING: Three medical intensive care units at two hospitals. PATIENTS: Five hundred eighty mechanically ventilated adult patients admitted between February 1, 2006 and January 31, 2008. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After adjusting weight based on the recorded fluid balance before enrollment, 21.9% of subjects were categorized into different body mass index categories than without this adjustment. We used a competing risk analysis with events of interest considered death during hospitalization and successful liberation from mechanical ventilation. We found no statistically significant difference between body mass index categories (<25 kg/m² vs. 25 to <30 kg/m² vs. ≥30 kg/m²) in the competing risks analyses when the results were unadjusted or adjusted for severity of illness and comorbidities. When the analyses were adjusted for the use of continuous infusions of opioids and/or sedatives and ventilator parameters (tidal volume per ideal body weight, positive end-expiratory pressure, and airway pressure), subjects with an overweight fluid-balance-adjusted body mass index had significantly lower hazard ratios for dying while hospitalized (adjusted hazard ratio 0.68 [95% confidence interval 0.47-0.99], p=.044), and those with an obese fluid-adjusted body mass index had significantly higher hazard ratios for successful extubation (adjusted hazard ratio 1.53 [95% confidence interval 1.14-2.06], p=.005). An analysis of longer-term mortality found lower adjusted hazard ratios for subjects with overweight (adjusted hazard ratio 0.74 [95% confidence interval 0.56-0.96]) and obese (adjusted hazard ratio 0.74 [95% confidence interval 0.59-0.94]) fluid-balance-adjusted body mass indices. CONCLUSIONS: Processes of provided care may affect the observed association between excess weight and outcomes for critically ill adults and should be considered when making inferences about observed results. It is unknown if disparities in processes of care are due to clinically justified reasons for variation, bias against heavier patients, or other reasons.

Continuity of care in intensive care units: a cluster-randomized trial of intensivist staffing.

RATIONALE: Little is known about the consequences of intensivists' work schedules, or intensivist continuity of care. OBJECTIVES: To assess the impact of weekend respite for intensivists, with consequent reduction in continuity of care, on them and their patients. METHODS: In five medical intensive care units (ICUs) in four academic hospitals we performed a prospective, cluster-randomized, alternating trial of two intensivist staffing schedules. Daily coverage by a single intensivist in half-month rotations (continuous schedule) was compared with weekday coverage by a single intensivist, with weekend cross-coverage by colleagues (interrupted schedule). We studied consecutive patients admitted to study units, and the intensivists working in four of the participating units. MEASUREMENTS AND MAIN RESULTS: The primary patient outcome was ICU length of stay (LOS);we also assessed hospital LOS and mortality rates. The primary intensivist outcome was physician burnout. Analysis was by multivariable regression. A total of 45 intensivists and 1,900 patients participated in the study. Continuity of care differed between schedules (patients with multiple intensivists = 28% under continuous schedule vs. 62% under interrupted scheduling; P < 0.0001). LOS and mortality were nonsignificantly higher under continuous scheduling (ΔICU LOS 0.36 d, P = 0.20; Δhospital LOS 0.34 d, P = 0.71; ICU mortality, odds ratio = 1.43, P = 0.12; hospital mortality, odds ratio = 1.17,P = 0.41). Intensivists experienced significantly higher burnout, work­home life imbalance, and job distress working under the continuous schedule. CONCLUSIONS: Work schedules where intensivists received weekend breaks were better for the physicians and, despite lower continuity of intensivist care, did not worsen outcomes for medical ICU patients.

Insurance type and sepsis-associated hospitalizations and sepsis-associated mortality among US adults: a retrospective cohort study.

INTRODUCTION: Socio-demographic and clinical factors associated with increased sepsis risk, including older age, non-white race and specific co-morbidities, are more common among patients with Medicare or Medicaid or no health insurance. We hypothesized that patients with Medicare and/or Medicaid or without health insurance have a higher risk of sepsis-associated hospitalization or sepsis-associated death than those with private health insurance. METHODS: We performed a retrospective cohort study of records from the 2003 Nationwide Inpatient Sample. We stratified the study cohort by Medicare age-qualification (18 to 64 and 65+ years old). We examined the association between insurance category and sepsis diagnosis and death among admissions involving sepsis. We used validated diagnostic codes to determine the presence of sepsis, co-morbidities and organ dysfunction and to provide risk-adjustment. RESULTS: Among patients 18 to 64 years old, those with Medicaid (adjusted odds ratio (AOR) 1.50), Medicare (AOR 1.96), Medicaid + Medicare (AOR 2.22) and the uninsured (AOR 1.18) had significantly higher risk-adjusted odds of a sepsis-associated admission than those with private insurance (all P < 0.0001). Those with Medicaid (AOR 1.17, P < 0.001) and those without insurance (AOR 1.45, P < 0.001) also had significantly higher adjusted odds of sepsis-associated hospital mortality than those with private insurance. Among those 65+ years old, those with Medicaid (AOR 1.43), Medicare alone (AOR 1.13) or Medicaid + Medicare (AOR 1.62) had significantly higher risk-adjusted odds of sepsis-associated admission than those with private insurance and Medicare (all P < 0.0001). Among sepsis patients 65+, uninsured patients had significantly higher risk-adjusted odds (AOR 1.45, P = 0.0048) and those with Medicare alone had significantly lower risk-adjusted odds (AOR 0.92, P = 0.0072) of hospital mortality than those with private insurance and Medicare. Lack of health insurance remained associated with sepsis-associated mortality after stratification of hospitals into quartiles based on rates of sepsis-associated admissions or mortality in both age strata. CONCLUSIONS: Risks of sepsis-associated hospitalization and sepsis-associated death vary by insurance. These increased risks were not fully explained by the available socio-demographic factors, co-morbidities or hospital rates of sepsis-related admissions or deaths.

An official American Thoracic Society systematic review: the association between health insurance status and access, care delivery, and outcomes for patients who are critically ill.

RATIONALE: One in three Americans under 65 years of age does not have health insurance during some portion of each year. Patients who are critically ill and lack health insurance may be at particularly high risk of morbidity and mortality due to the high cost of intensive care. OBJECTIVES: To systematically review the medical and nonmedical literature to determine whether differences in critical care access, delivery, and outcomes are associated with health insurance status. METHODS: Nine electronic databases (inception to 11 April 2008) were independently screened and abstracted in duplicate. MEASUREMENTS AND MAIN RESULTS: From 5,508 citations, 29 observational studies met eligibility criteria. Among the general U.S. population, patients who were uninsured were less likely to receive critical care services than those with insurance (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.55-0.56). Once admitted to the intensive care unit, patients who were uninsured had 8.5% (95% CI, 6.0-11.1) fewer procedures, were more likely to experience hospital discharge delays (OR 4.51; 95% CI, 1.46-13.93), and were more likely to have life support withdrawn (OR 2.80; 95% CI, 1.12-7.02). Lack of insurance may confer an independent risk of death for patients who are critically ill (OR 1.16; 95% CI, 1.01-1.33). Patients in managed care systems had 14.3% (95% CI, 11.5-17.2) fewer procedures in intensive care, but were also less likely to receive "potentially ineffective" care. Differences in unmeasured confounding factors may contribute to these findings. CONCLUSIONS: Patients in the United States who are critically ill and do not have health insurance receive fewer critical care services and may experience worse clinical outcomes. Improving preexisting health care coverage, as opposed to solely delivering more critical care services, may be one mechanism to reduce such disparities.

Delta inflation: a bias in the design of randomized controlled trials in critical care medicine.

INTRODUCTION: Mortality is the most widely accepted outcome measure in randomized controlled trials of therapies for critically ill adults, but most of these trials fail to show a statistically significant mortality benefit. The reasons for this are unknown. METHODS: We searched five high impact journals (Annals of Internal Medicine, British Medical Journal, JAMA, The Lancet, New England Journal of Medicine) for randomized controlled trials comparing mortality of therapies for critically ill adults over a ten year period. We abstracted data on the statistical design and results of these trials to compare the predicted delta (delta; the effect size of the therapy compared to control expressed as an absolute mortality reduction) to the observed delta to determine if there is a systematic overestimation of predicted delta that might explain the high prevalence of negative results in these trials. RESULTS: We found 38 trials meeting our inclusion criteria. Only 5/38 (13.2%) of the trials provided justification for the predicted delta. The mean predicted delta among the 38 trials was 10.1% and the mean observed delta was 1.4% (P < 0.0001), resulting in a delta-gap of 8.7%. In only 2/38 (5.3%) of the trials did the observed delta exceed the predicted delta and only 7/38 (18.4%) of the trials demonstrated statistically significant results in the hypothesized direction; these trials had smaller delta-gaps than the remainder of the trials (delta-gap 0.9% versus 10.5%; P < 0.0001). For trials showing non-significant trends toward benefit greater than 3%, large increases in sample size (380% - 1100%) would be required if repeat trials use the observed delta from the index trial as the predicted delta for a follow-up study. CONCLUSIONS: Investigators of therapies for critical illness systematically overestimate treatment effect size (delta) during the design of randomized controlled trials. This bias, which we refer to as "delta inflation", is a potential reason that these trials have a high rate of negative results."Absence of evidence is not evidence of absence."

Results from the national sepsis practice survey: predictions about mortality and morbidity and recommendations for limitation of care orders.

INTRODUCTION: Critically ill patients and families rely upon physicians to provide estimates of prognosis and recommendations for care. Little is known about patient and clinician factors which influence these predictions. The association between these predictions and recommendations for continued aggressive care is also understudied. METHODS: We administered a mail-based survey with simulated clinical vignettes to a random sample of the Critical Care Assembly of the American Thoracic Society. Vignettes represented a patient with septic shock with multi-organ failure with identical APACHE II scores and sepsis-associated organ failures. Vignettes varied by age (50 or 70 years old), body mass index (BMI) (normal or obese) and co-morbidities (none or recently diagnosed stage IIA lung cancer). All subjects received the vignettes with the highest and lowest mortality predictions from pilot testing and two additional, randomly selected vignettes. Respondents estimated outcomes and selected care for each hypothetical patient. RESULTS: Despite identical severity of illness, the range of estimates for hospital mortality (5th to 95th percentile range, 17% to 78%) and for problems with self-care (5th to 95th percentile range, 2% to 74%) was wide. Similar variation was observed when clinical factors (age, BMI, and co-morbidities) were identical. Estimates of hospital mortality and problems with self-care among survivors were significantly higher in vignettes with obese BMIs (4.3% and 5.3% higher, respectively), older age (8.2% and 11.6% higher, respectively), and cancer diagnosis (5.9% and 6.9% higher, respectively). Higher estimates of mortality (adjusted odds ratio 1.29 per 10% increase in predicted mortality), perceived problems with self-care (adjusted odds ratio 1.26 per 10% increase in predicted problems with self-care), and early-stage lung cancer (adjusted odds ratio 5.82) were independently associated with recommendations to limit care. CONCLUSIONS: The studied clinical factors were consistently associated with poorer outcome predictions but did not explain the variation in prognoses offered by experienced physicians. These observations raise concern that provided information and the resulting decisions about continued aggressive care may be influenced by individual physician perception. To provide more reliable and accurate estimates of outcomes, tools are needed which incorporate patient characteristics and preferences with physician predictions and practices.

Acquired weakness, handgrip strength, and mortality in critically ill patients.

RATIONALE: ICU-acquired paresis (ICUAP) is common in survivors of critical illness. There is significant associated morbidity, including prolonged time on the ventilator and longer hospital stay. However, it is unclear whether ICUAP is independently associated with mortality, as sicker patients are more prone and existing studies have not adjusted for this. OBJECTIVES: To test the hypothesis that ICUAP is independently associated with increased mortality. Secondarily, to determine if handgrip dynamometry is a concise measure of global strength and is independently associated with mortality. METHODS: A prospective multicenter cohort study was conducted in intensive care units (ICU) of five academic medical centers. Adults requiring at least 5 days of mechanical ventilation without evidence of preexisting neuromuscular disease were followed until awakening and were then examined for strength. MEASUREMENTS AND MAIN RESULTS: We measured global strength and handgrip dynamometry. The primary outcome was in-hospital mortality and secondary outcomes were hospital and ICU-free days, ICU readmission, and recurrent respiratory failure. Subjects with ICUAP (average MRC score of < 4) had longer hospital stays and required mechanical ventilation longer. Handgrip strength was lower in subjects with ICUAP and had good test performance for diagnosing ICUAP. After adjustment for severity of illness, ICUAP was independently associated with hospital mortality (odds ratio [OR], 7.8; 95% confidence interval [CI], 2.4-25.3; P = 0.001). Separately, handgrip strength was independently associated with hospital mortality (OR, 4.5; 95% CI, 1.5-13.6; P = 0.007). CONCLUSIONS: ICUAP is independently associated with increased hospital mortality. Handgrip strength is also independently associated with poor hospital outcome and may serve as a simple test to identify ICUAP. Clinical trial registered with www.clinicaltrials.gov (NCT00106665).

Glucose variability and mortality in patients with sepsis.

OBJECTIVE: Treatment and prevention of hyperglycemia has been advocated for subjects with sepsis. Glucose variability, rather than the glucose level, has also been shown to be an important factor associated with in-hospital mortality, in general, critically ill patients. Our objective was to determine the association between glucose variability and hospital mortality in septic patients and the expression of glucose variability that best reflects this risk. DESIGN: Retrospective, single-center cohort study. SETTING: Academic, tertiary care hospital. PATIENTS: Adult subjects hospitalized for >1 day, with a diagnosis of sepsis were included. INTERVENTIONS: None. MEASUREMENTS: Glucose variability was calculated for all subjects as the average and standard deviation of glucose, the mean amplitude of glycemic excursions, and the glycemic lability index. Hospital mortality was the primary outcome variable. Logistic regression was used to determine the odds of hospital death in relation to measures of glucose variability after adjustment for important covariates. MAIN RESULTS: Of the methods used to measure glucose variability, the glycemic lability index had the best discrimination for mortality (area under the curve = 0.67, p < 0.001). After adjustment for confounders, including the number of organ failures and the occurrence of hypoglycemia, there was a significant interaction between glycemic lability index and average glucose level, and the odds of hospital mortality. Higher glycemic lability index was not independently associated with mortality among subjects with average glucose levels above the median for the cohort. However, subjects with increased glycemic lability index, but lower average glucose values had almost five-fold increased odds of hospital mortality (odds ratio = 4.73, 95% confidence interval = 2.6-8.7) compared with those with lower glycemic lability index. CONCLUSIONS: Glucose variability is independently associated with hospital mortality in septic patients. Strategies to reduce glucose variability should be studied to determine whether they improve the outcomes of septic patients.

Year in review 2007: Critical Care--multiple organ failure and sepsis.

Several research papers published in Critical Care throughout 2007 examined the pathogenesis, diagnosis, treatment and prognosis of sepsis and multiorgan failure. The present review summarizes the findings and implications of the papers published on sepsis and multiorgan failure and places the research in the context of other work in the field.

The search-inference framework: a proposed strategy for novice clinical problem solving.

CONTEXT: Medical education in the clinical clerkship years emphasises the systematic collection and organisation of patient information to be combined with domain-specific knowledge of disease processes. Eventually, novice clinical problem solvers will learn to recognise patterns within the patient data ('illness scripts') which suggest the main diagnostic possibilities. Before novice problem solvers develop these illness scripts, pattern recognition may not be effective for solving clinical problems. METHODS: This discussion paper describes the application of a decision framework adapted from cognitive psychology (the search-inference framework) to basic medical problem solving. Emphasis is placed on problem solving by novices who have not yet developed a full compliment of illness scripts. CONCLUSIONS: The search-inference framework is similar to the approach taken by laypersons to diagnose their own symptoms or solve other problems. It may be especially useful for students who have not yet developed a sizeable repertoire of illness scripts, and the principles described may also be invoked by experienced clinicians confronting difficult clinical problems.

Important roles for macrophage colony-stimulating factor, CC chemokine ligand 2, and mononuclear phagocytes in the pathogenesis of pulmonary fibrosis.

RATIONALE: An increase in the number of mononuclear phagocytes in lung biopsies from patients with idiopathic pulmonary fibrosis (IPF) worsens prognosis. Chemokines that recruit mononuclear phagocytes, such as CC chemokine ligand 2 (CCL2), are elevated in bronchoalveolar lavage (BAL) fluid (BALF) from patients with IPF. However, little attention is given to the role of the mononuclear phagocyte survival and recruitment factor, macrophage colony-stimulating factor (M-CSF), in pulmonary fibrosis. OBJECTIVES: To investigate the role of mononuclear phagocytes and M-CSF in pulmonary fibrosis. METHODS: Wild-type, M-CSF-/-, or CCL2-/- mice received intraperitoneal bleomycin. Lung inflammation and fibrosis were measured by immunohistochemistry, ELISA, collagen assay, BAL differentials, real-time polymerase chain reaction, and Western blot analysis. Human and mouse macrophages were stimulated with M-CSF for CCL2 expression. BALF from patients with IPF was examined for M-CSF and CCL2. MEASUREMENTS AND MAIN RESULTS: M-CSF-/- and CCL2-/- mice had less lung fibrosis, mononuclear phagocyte recruitment, collagen deposition, and connective tissue growth factor (CTGF) expression after bleomycin administration than wild-type littermates. Human and mouse macrophages stimulated with M-CSF had increased CCL2 production, and intratracheal administration of M-CSF in mice induced CCL2 production in BALF. Finally, BALF from patients with IPF contained significantly more M-CSF and CCL2 than BALF from normal volunteers. Elevated levels of M-CSF were associated with elevated CCL2 in BALF and the diagnosis of IPF. CONCLUSIONS: These data suggest that M-CSF contributes to the pathogenesis of pulmonary fibrosis in mice and in patients with IPF through the involvement of mononuclear phagocytes and CCL2 production.

Laboratory testing in the intensive care unit.

Laboratory testing is ubiquitous among hospitalized patients and is more common among patients in the intensive care unit (ICU). Despite its high cost and prevalence, there are few data to support the current practice of laboratory testing in most ICUs. Although testing offers considerable potential benefits, it is not without risk, including misleading results, iatrogenic anemia, and therapeutic actions of uncertain benefit. Laboratory testing should be conducted as part of a therapeutic approach to a clinical problem, mindful of pretest probability of disease, the performance of the selected test, and the relative benefits and risks of testing. Considering the indication for a particular test can lead to a more rational approach to laboratory testing and better use of available tests.

Low-grade fever, erythematous rash in pregnant woman · Dx?

A 31-year-old woman presented to her obstetrician's office at 16 weeks' gestation with a 2-day history of low-grade fever and an erythematous rash measuring 1 x 4 cm on her right groin. She had a medical history of a penicillin allergy (urticarial) and her outdoor activities included gardening and picnicking. What's your diagnosis?