Marie Méan

Bench-to-bedside review: Candida infections in the intensive care unit

Invasive mycoses are life-threatening opportunistic infections and have emerged as a major cause of morbidity and mortality in critically ill patients. This review focuses on recent advances in our understanding of the epidemiology, diagnosis and management of invasive candidiasis, which is the predominant fungal infection in the intensive care unit setting. Candida spp. are the fourth most common cause of bloodstream infections in the USA, but they are a much less common cause of bloodstream infections in Europe. About one-third of episodes of candidaemia occur in the intensive care unit. Until recently, Candida albicans was by far the predominant species, causing up to two-thirds of all cases of invasive candidiasis. However, a shift toward non-albicans Candida spp., such as C. glabrata and C. krusei, with reduced susceptibility to commonly used antifungal agents, was recently observed. Unfortunately, risk factors and clinical manifestations of candidiasis are not specific, and conventional culture methods such as blood culture systems lack sensitivity. Recent studies have shown that detection of circulating β-glucan, mannan and antimannan antibodies may contribute to diagnosis of invasive candidiasis. Early initiation of appropriate antifungal therapy is essential for reducing the morbidity and mortality of invasive fungal infections. For decades, amphotericin B deoxycholate has been the standard therapy, but it is often poorly tolerated and associated with infusion-related acute reactions and nephrotoxicity. Azoles such as fluconazole and itraconazole provided the first treatment alternatives to amphotericin B for candidiasis. In recent years, several new antifungal agents have become available, offering additional therapeutic options for the management of Candida infections. These include lipid formulations of amphotericin B, new azoles (voriconazole and posaconazole) and echinocandins (caspofungin, micafungin and anidulafungin).

Prognostic Importance of Hyponatremia in Patients with Acute Pulmonary Embolism

RATIONALE Although associated with adverse outcomes in other cardiopulmonary conditions, the prognostic value of hyponatremia, a marker of neurohormonal activation, in patients with acute pulmonary embolism (PE) is unknown. OBJECTIVES To examine the associations between hyponatremia and mortality and hospital readmission rates for patients hospitalized with PE. METHODS We evaluated 13,728 patient discharges with a primary diagnosis of PE from 185 hospitals in Pennsylvania (January 2000 to November 2002). We used random-intercept logistic regression to assess the independent association between serum sodium levels at the time of presentation and mortality and hospital readmission within 30 days, adjusting for patient (race, insurance, severity of illness, use of thrombolytic therapy) and hospital factors (region, size, teaching status). MEASUREMENTS AND MAIN RESULTS Hyponatremia (sodium ≤135 mmol/L) was present in 2,907 patients (21.1%). Patients with a sodium level greater than 135, 130-135, and less than 130 mmol/L had a cumulative 30-day mortality of 8.0, 13.6, and 28.5% (P < 0.001), and a readmission rate of 11.8, 15.6, and 19.3% (P < 0.001), respectively. Compared with patients with a sodium greater than 135 mmol/L, the adjusted odds of dying were significantly greater for patients with a sodium 130-135 mmol/L (odds ratio [OR], 1.53; 95% confidence interval [CI], 1.33-1.76) and a sodium less than 130 mmol/L (OR, 3.26; 95% CI, 2.48-4.29). The adjusted odds of readmission were also increased for patients with a sodium of 130-135 mmol/L (OR, 1.28; 95% CI, 1.12-1.46) and a sodium less than 130 mmol/L (OR, 1.44; 95% CI, 1.02-2.02). CONCLUSIONS Hyponatremia is common in patients presenting with PE, and is an independent predictor of short-term mortality and hospital readmission.

Prospective, multicenter validation of prediction scores for major bleeding in elderly patients with venous thromboembolism

The Outpatient Bleeding Risk Index (OBRI) and the Kuijer, RIETE and Kearon scores are clinical prognostic scores for bleeding in patients receiving oral anticoagulants for venous thromboembolism (VTE). We prospectively compared the performance of these scores in elderly patients with VTE.

Validation of a clinical algorithm to identify low-risk patients with pulmonary embolism.

Summary.  Background: We previously derived a clinical prognostic algorithm to identify patients with pulmonary embolism (PE) who are at low risk of short‐term mortality and who could be safely discharged early or treated entirely in an outpatient setting. Objectives: To externally validate the clinical prognostic algorithm in an independent patient sample. Methods: We validated the algorithm in 983 consecutive patients prospectively diagnosed with PE at an emergency department of a university hospital. Patients with none of the algorithm’s 10 prognostic variables (age ≥ 70 years, cancer, heart failure, chronic lung disease, chronic renal disease, cerebrovascular disease, pulse ≥ 110 min–1, systolic blood pressure < 100 mmHg, oxygen saturation < 90%, and altered mental status) at baseline were defined as being at low risk. We compared 30‐day overall mortality among low‐risk patients, on the basis of the algorithm, between the validation sample and the original derivation sample. We also assessed the rate of PE‐related and bleeding‐related mortality among low‐risk patients. Results: Overall, the algorithm classified 16.3% of patients with PE as being at low risk. Mortality at 30 days was 1.9% among low‐risk patients, and did not differ between the validation sample and the original derivation sample. Among low‐risk patients, only 0.6% died from definite or possible PE, and 0% died from bleeding. Conclusions: This study validates an easy‐to‐use, clinical prognostic algorithm for PE that accurately identifies patients with PE who are at low risk of short‐term mortality. Patients who are at low risk according to our algorithm are potential candidates for less costly outpatient treatment.

Prospective comparison of clinical prognostic scores in elderly patients with pulmonary embolism

Summary.  Background:  The Geneva Prognostic Score (GPS), the Pulmonary Embolism Severity Index (PESI) and its simplified version (sPESI) are well‐known clinical prognostic scores for a pulmonary embolism (PE).

Elevated Admission Glucose and Mortality in Patients With Acute Pulmonary Embolism

OBJECTIVE Although associated with adverse outcomes in other cardiopulmonary conditions, the prognostic value of elevated glucose in patients with acute pulmonary embolism (PE) is unknown. We sought to examine the association between glucose levels and mortality and hospital readmission rates for patients with PE. RESEARCH DESIGN AND METHODS We evaluated 13,621 patient discharges with a primary diagnosis of PE from 185 acute care hospitals in Pennsylvania (from January 2000 to November 2002). Admission glucose levels were analyzed as a categorical variable (≤110, >110–140, >140–170, >170–240, and >240 mg/dL). The outcomes were 30-day all-cause mortality and hospital readmission. We used random-intercept logistic regression to assess the independent association between admission glucose levels and mortality and hospital readmission, adjusting for patient (age, sex, race, insurance, comorbid conditions, severity of illness, laboratory parameters, and thrombolysis) and hospital (region, size, and teaching status) factors. RESULTS Elevated glucose (>110 mg/dL) was present in 8,666 (63.6%) patients. Patients with a glucose level ≤110, >110–140, >140–170, >170–240, and >240 mg/dL had a 30-day mortality of 5.6, 8.4, 12.0, 15.6, and 18.3%, respectively (P < 0.001). Compared with patients with a glucose level ≤110 mg/dL, the adjusted odds of dying were greater for patients with a glucose level >110–140 (odds ratio 1.19 [95% CI 1.00–1.42]), >140–170 (1.44 [1.17–1.77]), >170–240 (1.54 [1.26–1.90]), and >240 mg/dL (1.60 [1.26–2.03]), with no difference in the odds of hospital readmission. CONCLUSIONS In patients with acute PE, elevated admission glucose is common and independently associated with short-term mortality.

The inter-rater reliability of the Pulmonary Embolism Severity Index

The Pulmonary Embolism Severity Index (PESI) is a validated clinical prognostic model for patients with acute pulmonary embolism (PE). Our goal was to assess the PESIs inter-rater reliability in patients diagnosed with PE. We prospectively identified consecutive patients diagnosed with PE in the emergency department of a Swiss teaching hospital. For all patients, resident and attending physician raters independently collected the 11 PESI variables. The raters then calculated the PESI total point score and classified patients into one of five PESI risk classes (I-V) and as low (risk classes I/II) versus higher-risk (risk classes III-V). We examined the inter-rater reliability for each of the 11 PESI variables, the PESI total point score, assignment to each of the five PESI risk classes, and classification of patients as low versus higher-risk using kappa (κ) and intra-class correlation coefficients (ICC). Among 48 consecutive patients with an objective diagnosis of PE, reliability coefficients between resident and attending physician raters were > 0.60 for 10 of the 11 variables comprising the PESI. The inter-rater reliability for the PESI total point score (ICC: 0.89, 95% CI: 0.81-0.94), PESI risk class assignment (κ: 0.81, 95% CI: 0.66-0.94), and the classification of patients as low versus higher-risk (κ: 0.92, 95% CI: 0.72-0.98) was near perfect. Our results demonstrate the high reproducibility of the PESI, supporting the use of the PESI for risk stratification of patients with PE.

Substance use and suicidal conduct: A study of adolescents hospitalized for suicide attempt and ideation

AIM To study the prevalence of psychoactive substance use disorder (PSUD) among suicidal adolescents, psychoactive substance intoxication at the moment of the attempt, and the association between PSUD at baseline and either occurrence of suicide or repetition of suicide attempt(s). METHODS 186 adolescents aged 16 to 21 y hospitalized for suicide attempt or overwhelming suicidal ideation were included (T0); 148 of them were traced again for evaluations after 6 mo (T1) and/or 18 mo (T2). DSM-IV diagnoses were assessed each time using the Mini International Neuropsychiatric Interview. RESULTS At T0, 39.2% of the subjects were found to have a PSUD. Among them, a significantly higher proportion was intoxicated at the time of the attempt than those without PSUD (44.3% vs 25.4%). Among the 148 adolescents who could be traced at either T1 or T2, two died from suicide and 30 repeated suicide attempts once or more times. A marginally significant association was found between death by suicide/repetition of suicide attempt and alcohol abuse/dependence at baseline (OR=3.3, 95% CI 0.7-15.0; OR=2.6, 95% CI 0.7-9.3). More than one suicide attempt before admission to hospital at T0 (OR=3.2, 95% CI 1.1-10.0) and age over 19 y at T0 (OR=3.2, 95% CI 1.1-9.2) were independently associated with the likelihood of death by suicide or repetition of suicide attempt. CONCLUSION Among adolescents hospitalized for suicide attempt or overwhelming suicidal ideation, the risk of death or repetition of attempt is high and is associated with previous suicide attempts--especially among older adolescents--and also marginally associated with PSUD; these adolescents should be carefully evaluated for such risks and followed up once discharged from the hospital.

Physical Activity and Risk of Bleeding in Elderly Patients Taking Anticoagulants

Although the possibility of bleeding during anticoagulant treatment may limit patients from taking part in physical activity, the association between physical activity and anticoagulation‐related bleeding is uncertain.

Predictors and Causes of Long-Term Mortality in Elderly Patients with Acute Venous Thromboembolism: A Prospective Cohort Study

BACKGROUND Long-term predictors and causes of death are understudied in elderly patients with acute venous thromboembolism. METHODS We prospectively followed up 991 patients aged ≥65 years with acute venous thromboembolism in a multicenter Swiss cohort study. The primary outcome was overall mortality. We explored the association between patient baseline characteristics and mortality, adjusting for other baseline variables and periods of anticoagulation as a time-varying covariate. Causes of death over time were adjudicated by a blinded, independent committee. RESULTS The median age was 75 years. During a median follow-up period of 30 months, 206 patients (21%) died. Independent predictors of overall mortality were age (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.05-1.65, per decade), active cancer (HR, 5.80; 95% CI, 4.22-7.97), systolic blood pressure <100 mm Hg (HR, 2.77; 95% CI, 1.56-4.92), diabetes mellitus (HR, 1.50; 95% CI, 1.02-2.22), low physical activity level (HR, 1.92; 95% CI, 1.38-2.66), polypharmacy (HR, 1.41; 95% CI, 1.01-1.96), anemia (HR, 1.48; 95% CI, 1.07-2.05), high-sensitivity C-reactive protein >40 mg/L (HR, 1.88; 95% CI, 1.36-2.60), ultra-sensitive troponin >14 pg/mL (HR, 1.54; 95% CI, 1.06-2.25), and D-dimer >3000 ng/mL (HR, 1.45; 95% CI, 1.04-2.01). Cancer (34%), pulmonary embolism (18%), infection (17%), and bleeding (6%) were the most common causes of death. CONCLUSIONS Elderly patients with acute venous thromboembolism have a substantial long-term mortality, and several factors, including polypharmacy and a low physical activity level, are associated with long-term mortality. Cancer, pulmonary embolism, infections, and bleeding are the most common causes of death in the elderly with venous thromboembolism.