Christian Woods

The validation and reproducibility of the pulmonary embolism severity index

Summary.  Background: Rapid, accurate risk stratification is paramount in managing patients with acute pulmonary embolism (PE). The PE Severity Index (PESI) is a simple tool that risk stratifies patients with acute PE. Objectives: We sought to validate the PESI as a predictor of short‐ and intermediate‐term mortality and to determine the inter‐rater variability. Patients/Methods: We retrospectively identified all patients with acute PE between October 2007 and February 2009. Two clinicians reviewed charts and independently scored PESI blinded to each other and to patient outcomes. Thirty‐ and 90‐day mortality served as study endpoints and vital status was assessed via the Social Security Death Index. To facilitate analyses, raw PESI score was converted into risk class groups (I–V) and further dichotomized into low risk (I–II) vs. high risk (III–V) groups. Intraclass correlation and the kappa statistic were used to determine inter‐rater variability. Results: The cohort included 302 subjects (mean age, 59.7 ± 17.2 years; 44% male). All‐cause 30‐ and 90‐day mortalities were 3.0% and 4.0%, respectively. The mortality rate increased as raw PESI score increased. Risk of death correlated with risk class (P < 0.001). There were no deaths in risk classes I–III, but 30‐ and 90‐day mortality for class V were 9.2% and 10.5%, respectively. Overall, mean PESI scores were similar between observers: 103.3 ± 39.3 and 96.5 ± 37.6 (P = NS). The inter‐rater variability was good (kappa = 0.69; P < 0.0001). Conclusions: The PESI correlates with 30‐ and 90‐day mortality. It represents a reproducible scoring tool to risk stratify patients with acute PE.

A1C Underestimates Glycemia in HIV Infection

OBJECTIVE The objective of this study was to determine the relationship between A1C and glycemia in HIV infection. RESEARCH DESIGN AND METHODS We completed a prospective cross-sectional study of 100 HIV-infected adults with type 2 diabetes (77%) or fasting hyperglycemia (23%) with measured glucose, A1C, mean corpuscular volume (MCV), and fructosamine. A total of 200 HIV-uninfected type 2 diabetic subjects matched for key demographic characteristics served as control subjects. RESULTS Relative to the control subjects, A1C underestimated glucose by 29 ± 4 mg/dl in the HIV-infected subjects. Current nucleoside reverse transcriptase inhibitors (NRTIs), higher MCV and hemoglobin, and lower HIV RNA and haptoglobin were associated with greater A1C-glucose discordance. However, only MCV and current NTRI use, in particular abacavir, remained significant predictors in multivariate analyses. Fructosamine more closely reflected glycemia in the HIV-infected subjects. CONCLUSIONS A1C underestimates glycemia in HIV-infected patients and is related to NRTI use. Use of abacavir and increased MCV were key correlates in multivariate analyses. Fructosamine may be more appropriate in this setting.

Increased prevalence of albuminuria in HIV-infected adults with diabetes.

Objective HIV and type 2 diabetes are known risk factors for albuminuria, but no previous reports have characterized albuminuria in HIV-infected patients with diabetes. Research Design and Methods We performed a cross-sectional study including 73 HIV-infected adults with type 2 diabetes, 82 HIV-infected non-diabetics, and 61 diabetic control subjects without HIV. Serum creatinine >1.5 mg/dL was exclusionary. Albuminuria was defined as urinary albumin/creatinine ratio >30 mg/g. Results The prevalence of albuminuria was significantly increased among HIV-infected diabetics (34% vs. 13% of HIV non-diabetic vs. 16% diabetic control, p = 0.005). HIV status and diabetes remained significant predictors of albuminuria after adjusting for age, race, BMI, and blood pressure. Albumin/creatinine ratio correlated significantly with HIV viral load (r = 0.28, p = 0.0005) and HIV-infected subjects with albuminuria had significantly greater cumulative exposure to abacavir (p = 0.01). In an adjusted multivariate regression analysis of HIV-infected subjects, the diagnosis of diabetes (p = 0.003), higher HIV viral load (p = 0.03) and cumulative exposure to abacavir (p = 0.0009) were significant independent predictors of albuminuria. Conclusions HIV and diabetes appear to have additive effects on albuminuria which is also independently associated with increased exposure to abacavir and HIV viral load. Future research on the persistence, progression and management of albuminuria in this unique at-risk population is needed.

Domestically Acquired Seoul Virus Causing Hemorrhagic Fever with Renal Syndrome—Maryland, 2008

Hantaviruses are rodent-borne viruses capable of causing human disease. The Seoul virus is a hantavirus that causes hemorrhagic fever with renal syndrome in East Asia. To our knowledge, we report the first domestically acquired case of hemorrhagic fever with renal syndrome caused by the Seoul virus, confirmed by serology testing, reverse-transcriptase polymerase chain reaction, and nucleotide sequence analysis. The patient presented with myalgias and fever, and developed acute renal failure.

The Role for Optical Density in Heparin-Induced Thrombocytopenia: A Cohort Study

BACKGROUND Heparin-induced thrombocytopenia (HIT) is a serious complication of heparin utilization. An enzyme-linked immunosorbent assay (ELISA) is usually performed to assist in the diagnosis of HIT. ELISAs tend to be sensitive but lack specificity. We sought to use a new cutoff to define a positive HIT ELISA. METHODS We conducted a prospective observational study of hospitalized patients undergoing ELISA testing. All patients who underwent ELISA testing were eligible for inclusion (n = 496). Irrespective of the results, all subjects had confirmatory testing with a serotonin release assay (SRA). We compared a threshold optical density (OD) > 1.00 to the current definition of a positive ELISA (OD > 0.40) as a screening test for a positive SRA. We used sensitivity, specificity, and area under the receiver operating curve to determine whether an OD > 1.00 would improve diagnostic accuracy for HIT. RESULTS The SRA was positive in 10 patients (prevalence, 2.0%). Adjusting the definition of a positive HIT ELISA to > 1.00 maintained the sensitivity and negative predictive value at 100% in the cohort. The positive predictive value of the higher cutoff OD was more than triple the positive predictive value of an OD > 0.40 (41.7% vs 13.3%). No patient with a positive SRA had an OD measurement ≤ 1.00. CONCLUSIONS Increasing the OD threshold enhances specificity without noticeably compromising sensitivity. Altering the definition of the HIT ELISA could prevent unnecessary testing and/or treatment with non-heparin-based anticoagulants in patients with possible HIT. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT00946400; URL: www.clinicaltrials.gov.

The CD8+HLA-DR+ T cells expanded in HIV-1 infection are qualitatively identical to those from healthy controls

HIV‐induced immune activation leads to expansion of a subset of human CD8+ T cells expressing HLA‐DR antigens. Expansion of CD8+HLA‐DR+ T cells can be also observed in non‐HIV settings including several autoimmune diseases and aging. Although these cells are felt to represent “immune exhaustion” and/or to be anergic, their precise role in host defense has remained unclear. Here, we report that this subset of cells exhibits a restricted repertoire, shows evidence of multiple rounds of division, but lacks markers of recent TCR engagement. Detailed cell cycle analysis revealed that compared with their CD8+HLA‐DR− counterpart, the CD8+HLA‐DR+ T‐cell pool contained an increased fraction of cells in S‐phase with elevated levels of the G2/M regulators: cyclin A2, CDC25C, Cdc2 (CDK1), indicating that these cells are not truly anergic but rather experiencing proliferation in vivo. Together, these data support a hypothesis that antigen stimulation leads to the initial expansion of a CD8+ pool of cells in vivo that undergo further expansion independent of ongoing TCR engagement. No qualitative differences were noted between CD8+HLA‐DR+ cells from HIV+ and HIV− donors, indicating that the generation of CD8+HLA‐DR+ T cells is a part of normal immune regulation that is exaggerated in the setting of HIV‐1 infection.

Methicillin-resistant Staphylococcus aureus pneumonia in adults.

Methicillin-resistant Staphylococcus aureus (MRSA) has become one of the leading etiologies of nosocomial pneumonia as a result of an increase in staphylococcal infections caused by methicillin-resistant strains paired with extended ventilatory support of critically, and often, chronically ill patients. The prevalence of community-acquired MRSA pneumonia, which historically affects younger patients and is often preceded by an influenza-like illness, is also increasing. A high index of suspicion and early initiation of appropriate antibiotics are key factors for the successful treatment of this disease. Even with early diagnosis and appropriate treatment, MRSA pneumonia still carries an unacceptably high mortality rate. This article will review historical differences between hospital-acquired and community-acquired MRSA pneumonia, as well as, clinical features of, diagnosis and treatment of MRSA pneumonia.

Impact of vancomycin minimum inhibitory concentration on mortality among critically ill patients with methicillin-resistant Staphylococcus aureus bacteremia.

We retrospectively evaluated 99 intensive care unit patients with methicillin-resistant Staphylococcus aureus bacteremia to determine whether having a vancomycin minimum inhibitory concentration (MIC) of 2 mg/L affected mortality. This MIC was found in 5.1% of patients and was associated with the probability of death (adjusted odds ratio, 13.9 [95% confidence interval, 1.1-171.2]) independent of other factors.

Comparing the pulmonary embolism severity index and the prognosis in pulmonary embolism scores as risk stratification tools

BACKGROUND Multiple risk stratification scoring systems exist to forecast outcomes in patients with acute pulmonary embolism (PE). OBJECTIVE We evaluated the comparative validity of the PE severity index (PESI) and the prognosis in pulmonary embolism (PREP) scores to predict mortality in acute PE. DESIGN Retrospective observational cohort study. SETTING Washington Hospital Center, Washington, DC. PATIENTS Consecutive adults (aged >18 years) diagnosed with acute PE. INTERVENTION The PESI and PREP scores were calculated. MEASUREMENTS Raw PESI scores were segregated into risk class (I-V) and then dichotomized into low (I-II) versus high (III-V) risk groups; the raw PREP scores were divided into low (0-7) versus high (>7) risk groups. The primary endpoint was 30-day and 90-day mortality. We determined the negative predictive value and computed the area under the receiver operating characteristics (AUROC) curves to compare the ability of these scoring tools. RESULTS The cohort consisted of 302 subjects. Thirty-day mortality was 3.0%, and 4.0% died within 90 days. The PESI and the PREP performed similarly (PESI AUROC: 0.858 [95% confidence interval (CI), 0.773-0.943] vs 0.719 [95% CI, 0.563-0.875] for PREP). Segregating these scores into risk categories did not affect their discriminatory power (AUROC: 0.684 [95% CI, 0.559-0.810] for PESI and 0.790 [95% CI, 0.679-0.903] for PREP). The negative predictive value for death of being classified as low risk by the PESI or PREP was 100% and 99%, respectively. CONCLUSIONS The PREP score performed comparably to the PESI score for identifying PE patients at low risk for short-term and intermediate-term mortality.

Pneumonia in the Long-Term Resident

Pneumonia in the long-term resident is common. It is associated with high morbidity and mortality. However, diagnosis and management of pneumonia in long-term care residents is challenging. This article provides an overview of the epidemiology, pathophysiology, diagnostic challenges, and management recommendations for pneumonia in this setting.