Robin Ruthazer

Missed Diagnoses of Acute Cardiac Ischemia in the Emergency Department

BACKGROUND Discharging patients with acute myocardial infarction or unstable angina from the emergency department because of missed diagnoses can have dire consequences. We studied the incidence of, factors related to, and clinical outcomes of failure to hospitalize patients with acute cardiac ischemia. METHODS We analyzed clinical data from a multicenter, prospective clinical trial of all patients with chest pain or other symptoms suggesting acute cardiac ischemia who presented to the emergency departments of 10 U.S. hospitals. RESULTS Of 10,689 patients, 17 percent ultimately met the criteria for acute cardiac ischemia (8 percent had acute myocardial infarction and 9 percent had unstable angina), 6 percent had stable angina, 21 percent had other cardiac problems, and 55 percent had noncardiac problems. Among the 889 patients with acute myocardial infarction, 19 (2.1 percent) were mistakenly discharged from the emergency department (95 percent confidence interval, 1.1 to 3.1 percent); among the 966 patients with unstable angina, 22 (2.3 percent) were mistakenly discharged (95 percent confidence interval, 1.3 to 3.2 percent). Multivariable analysis showed that patients who presented to the emergency department with acute cardiac ischemia were more likely not to be hospitalized if they were women less than 55 years old (odds ratio for discharge, 6.7; 95 percent confidence interval, 1.4 to 32.5), were nonwhite (odds ratio, 2.2; 1.1 to 4.3), reported shortness of breath as their chief symptom (odds ratio, 2.7; 1.1 to 6.5), or had a normal or nondiagnostic electrocardiogram (odds ratio, 3.3; 1.7 to 6.3). Patients with acute infarction were more likely not to be hospitalized if they were nonwhite (odds ratio for discharge, 4.5; 95 percent confidence interval, 1.8 to 11.8) or had a normal or nondiagnostic electrocardiogram (odds ratio, 7.7; 95 percent confidence interval, 2.9 to 20.2). For the patients with acute infarction, the risk-adjusted mortality ratio for those who were not hospitalized, as compared with those who were, was 1.9 (95 percent confidence interval, 0.7 to 5.2), and for the patients with unstable angina, it was 1.7 (95 percent confidence interval, 0.2 to 17.0). CONCLUSIONS The percentage of patients who present to the emergency department with acute myocardial infarction or unstable angina who are not hospitalized is low, but the discharge of such patients is associated with increased mortality. Failure to hospitalize is related to race, sex, and the absence of typical features of cardiac ischemia. Continued efforts to reduce the number of missed diagnoses are warranted.

Factors associated with candidemia caused by non-albicans Candida species versus Candida albicans in the intensive care unit.

BACKGROUND Candida albicans has been the most common cause of fungal bloodstream infections (BSIs) in intensive care units (ICUs); however, infections due to non-albicans Candida species have been increasing in prevalence. We examined factors associated with BSIs due to non-albicans Candida species, compared with C. albicans BSIs, in an ICU patient population. METHODS For our case-comparator study, we identified consecutive adult ICU patients with BSIs due to non-albicans Candida species or C. albicans at 2 tertiary care hospitals during the period 1995-2005. Data collected included demographic characteristics, comorbidities, exposure to antibiotics and antifungals, and ICU-related factors, such as total parenteral nutrition, blood product transfusions, invasive procedures, central venous catheter use, hemodialysis, and mechanical ventilation. We built a multivariable logistic regression model that identified variables that differentiate BSIs due to non-albicans Candida species from BSIs due to C. albicans. RESULTS There were 67 patients with BSIs due to non-albicans Candida species and 79 patients with C. albicans BSIs. Variables were adjusted for time at risk. In multivariable models, factors associated with an increased risk of BSIs due to non-albicans Candida species, compared with C. albicans BSIs, included fluconazole exposure (odds ratio, 11.6; 95% confidence interval, 2.28-58.8), central venous catheter exposure (odds ratio, 1.95; 95% confidence interval, 1.10-3.47), and mean number of antibiotics per day (odds ratio, 2.31; 95% confidence interval, 0.71-7.54). Total parenteral nutrition exposure was associated with a decreased risk (odds ratio, 0.16; 95% confidence interval, 0.05-0.47) of BSIs due to non-albicans Candida species, compared with C. albicans BSIs. Duration of stay in the ICU was not significantly different between the 2 groups. Specific antibiotics, such as vancomycin and piperacillin-tazobactam, were not independently associated with BSI due to non-albicans Candida species. CONCLUSIONS Receipt of fluconazole and central venous catheter exposure were associated with an increased risk of BSI due to non-albicans Candida species, and total parenteral nutrition was associated with a decreased risk of BSI due to non-albicans Candida species, compared with BSI due to C. albicans. Patients without characteristics of infection due to non-albicans Candida species might benefit from empirical antifungal therapy with fluconazole.

Persistence of Immunoglobulin M or Immunoglobulin G Antibody Responses to Borrelia burgdorferi 10–20 Years after Active Lyme Disease

The interpretation of serological results for patients who had Lyme disease many years ago is not well defined. We studied the serological status of 79 patients who had had Lyme disease 10-20 years ago and did not currently have signs or symptoms of active Lyme disease. Of the 40 patients who had had early Lyme disease alone, 4 (10%) currently had IgM responses to Borrelia burgdorferi, and 10 (25%) still had IgG reactivity to the spirochete, as determined by a 2-test approach (enzyme-linked immunosorbent assay and Western blot). Of the 39 patients who had had Lyme arthritis, 6 (15%) currently had IgM responses and 24 (62%) still had IgG reactivity to the spirochete. IgM or IgG antibody responses to B. burgdorferi may persist for 10-20 years, but these responses are not indicative of active infection.

Out-of-Hospital Administration of Intravenous Glucose-Insulin-Potassium in Patients With Suspected Acute Coronary Syndromes: The IMMEDIATE Randomized Controlled Trial

CONTEXT Laboratory studies suggest that in the setting of cardiac ischemia, immediate intravenous glucose-insulin-potassium (GIK) reduces ischemia-related arrhythmias and myocardial injury. Clinical trials have not consistently shown these benefits, possibly due to delayed administration. OBJECTIVE To test out-of hospital emergency medical service (EMS) administration of GIK in the first hours of suspected acute coronary syndromes (ACS). DESIGN, SETTING, AND PARTICIPANTS Randomized, placebo-controlled, double-blind effectiveness trial in 13 US cities (36 EMS agencies), from December 2006 through July 31, 2011, in which paramedics, aided by electrocardiograph (ECG)-based decision support, randomized 911 (871 enrolled) patients (mean age, 63.6 years; 71.0% men) with high probability of ACS. INTERVENTION Intravenous GIK solution (n = 411) or identical-appearing 5% glucose placebo (n = 460) administered by paramedics in the out-of-hospital setting and continued for 12 hours. MAIN OUTCOME MEASURES The prespecified primary end point was progression of ACS to myocardial infarction (MI) within 24 hours, as assessed by biomarkers and ECG evidence. Prespecified secondary end points included survival at 30 days and a composite of prehospital or in-hospital cardiac arrest or in-hospital mortality, analyzed by intent-to-treat and by presentation with ST-segment elevation. RESULTS There was no significant difference in the rate of progression to MI among patients who received GIK (n = 200; 48.7%) vs those who received placebo (n = 242; 52.6%) (odds ratio [OR], 0.88; 95% CI, 0.66-1.13; P = .28). Thirty-day mortality was 4.4% with GIK vs 6.1% with placebo (hazard ratio [HR], 0.72; 95% CI, 0.40-1.29; P = .27). The composite of cardiac arrest or in-hospital mortality occurred in 4.4% with GIK vs 8.7% with placebo (OR, 0.48; 95% CI, 0.27-0.85; P = .01). Among patients with ST-segment elevation (163 with GIK and 194 with placebo), progression to MI was 85.3% with GIK vs 88.7% with placebo (OR, 0.74; 95% CI, 0.40-1.38; P = .34); 30-day mortality was 4.9% with GIK vs 7.7% with placebo (HR, 0.63; 95% CI, 0.27-1.49; P = .29). The composite outcome of cardiac arrest or in-hospital mortality was 6.1% with GIK vs 14.4% with placebo (OR, 0.39; 95% CI, 0.18-0.82; P = .01). Serious adverse events occurred in 6.8% (n = 28) with GIK vs 8.9% (n = 41) with placebo (P = .26). CONCLUSIONS Among patients with suspected ACS, out-of-hospital administration of intravenous GIK, compared with glucose placebo, did not reduce progression to MI. Compared with placebo, GIK administration was not associated with improvement in 30-day survival but was associated with lower rates of the composite outcome of cardiac arrest or in-hospital mortality. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00091507.

An index to identify stroke-related vs incidental patent foramen ovale in cryptogenic stroke

Objective: We aimed to create an index to stratify cryptogenic stroke (CS) patients with patent foramen ovale (PFO) by their likelihood that the stroke was related to their PFO. Methods: Using data from 12 component studies, we used generalized linear mixed models to predict the presence of PFO among patients with CS, and derive a simple index to stratify patients with CS. We estimated the stratum-specific PFO-attributable fraction and stratum-specific stroke/TIA recurrence rates. Results: Variables associated with a PFO in CS patients included younger age, the presence of a cortical stroke on neuroimaging, and the absence of these factors: diabetes, hypertension, smoking, and prior stroke or TIA. The 10-point Risk of Paradoxical Embolism score is calculated from these variables so that the youngest patients with superficial strokes and without vascular risk factors have the highest score. PFO prevalence increased from 23% (95% confidence interval [CI]: 19%–26%) in those with 0 to 3 points to 73% (95% CI: 66%–79%) in those with 9 or 10 points, corresponding to attributable fraction estimates of approximately 0% to 90%. Kaplan-Meier estimated stroke/TIA 2-year recurrence rates decreased from 20% (95% CI: 12%–28%) in the lowest Risk of Paradoxical Embolism score stratum to 2% (95% CI: 0%–4%) in the highest. Conclusion: Clinical characteristics identify CS patients who vary markedly in PFO prevalence, reflecting clinically important variation in the probability that a discovered PFO is likely to be stroke-related vs incidental. Patients in strata more likely to have stroke-related PFOs have lower recurrence risk.

Clinical Features of Emergency Department Patients Presenting with Symptoms Suggestive of Acute Cardiac Ischemia: A Multicenter Study

Identification of patients with acute cardiac ischemia (ACI) remains challenging. The object of this study was to examine the role of clinical findings in the diagnosis/triage of emergency department (ED) patients with symptoms suggestive of ACI. The study was designed as a secondary data analysis of a multicenter prospective controlled clinical trial. It was set in 10 midwest, southeast, and northeast U.S. hospitals, and 10,689 patients with chest pain or other symptoms suggesting ACI presenting from May 1993 to December 1993, participated. The results indicated that ACI patients were more likely to have chest pain as a chief complaint or presenting symptom (P = 0.001). The presenting symptom of nausea was more commonly associated with a final diagnosis of ACI (P = 0.003). Shortness of breath as the chief complaint and presenting symptoms of abdominal pain, nausea, dizziness, and fainting were less frequent among patients with a final diagnosis of ACI (P = 0.001). A past history of diabetes mellitus, myocardial infarction, or angina pectoris was more frequently associated with a final diagnosis of ACI (P = 0.001). A lower pulse rate in patients with a final diagnosis of ACI (P = 0.001) was not considered clinically significant. Median first and highest systolic blood pressures (SBPs) were higher, median lowest SBPs were lower, median diastolic blood pressure of the lowest SBPs were lower, and initial and highest pulse pressures were wider in patients with a final diagnosis of ACl (P = 0.001). On arrival, these blood pressure variables in AMI patients, subsequently classified as Killip class 4, were above the threshold for this classification. Rales were more commonly present in patients with a final diagnosis of ACI (P= 0.001). All primary ST-segment abnormalities, Q waves, and T-wave abnormalities, except T-wave flattening, were seen more frequently in patients with a final diagnosis ACI (P= 0.001). Normal ECGs were more frequently associated with a non-ACI final diagnosis, yet 20% of AMI patients and 37% of Unstable Angina Pectoris (UAP) patients had normal ECGs. It can be concluded that certain clinical features can help to identify ED patients with ACI. Initially normal ECGs can be seen in 20% of patients with AMI and 37% of patients with UAP. Patients with ACI can present with “normal” blood pressures and develop cardiogenic shock. Clinical outcome data for ACI patients are presented.

The Stroke–Thrombolytic Predictive Instrument A Predictive Instrument for Intravenous Thrombolysis in Acute Ischemic Stroke

Background and Purpose— Many patients with ischemic stroke eligible for recombinant tissue plasminogen activator (rt-PA) are not treated in part because of the risks and benefits perceived by treating physicians. Therefore, we aimed to develop a Stroke-Thrombolytic Predictive Instrument (TPI) to aid physicians considering thrombolysis for stroke. Methods— Using data from 5 major randomized clinical trials (n=2184) testing rt-PA in the 0- to 6-hour window, we developed logistic regression equations using clinical variables as potential predictors of a good outcome (modified Rankin Scale score ≤1) and of a catastrophic outcome (modified Rankin Scale score ≥5), with and without rt-PA. The models were internally validated using bootstrap re-sampling. Results— To predict good outcome, in addition to rt-PA treatment, 7 variables significantly affected prognosis and/or the treatment-effect of rt-PA: age, diabetes, stroke severity, sex, previous stroke, systolic blood pressure, and time from symptom onset. To predict catastrophic outcome, only age, stroke severity, and serum glucose were significant; rt-PA treatment was not. For patients treated within 3 hours, the median predicted probability of a good outcome with rt-PA was 42.9% (interquartile range [IQR]=18.6% to 64.7%) versus 25.3% (IQR=9.8% to 46.2%) without rt-PA; the median predicted absolute benefit was 12.5% (IQR=5.1% to 21.0%). The median probability for a catastrophic outcome, with or without, rt-PA was 15.2% (IQR=8.0% to 31.2%). The area under the receiver-operator characteristic curve was 0.788 for the model predicting good outcome and 0.775 for the model predicting bad outcome. Conclusions— The Stroke-TPI predicts good and bad functional outcomes with and without thrombolysis. Incorporated into a usable tool, it may assist in decision-making.

Optimizing staging for hepatocellular carcinoma before liver transplantation: A retrospective analysis of the UNOS/OPTN database

Assignment of liver allocation priority for hepatocellular carcinoma is predicated on accurate imaging staging. We analyzed radiographically defined stage (radiologic stage [RS]) at listing and most recent extension and pathologic stage (PS) data from 789 liver transplant recipients for whom no pretransplant ablative treatment was given. There were no predetermined imaging or pathological protocols in this retrospective analysis of wait list data. Seventy‐two (9.1%), 690 (87.5%), and 27 (3.4%) were listed as stage 1, 2 and >2, respectively. Computed tomography (CT) scan alone (46.4%), magnetic resonance image scan alone (37.1%), ultrasound alone (1.3%), and multiple imaging studies (15.2%) were used with no difference in time to transplant for listing or most recent scan among the recipient groups. Overall accuracy (RS = PS) was 44.1% and was not different if original listing RS or most recent RS was used for comparison with PS. No one type of imaging technique had superior accuracy (P = 0.13); however, CT scan used alone or in combination compared to not being used at all, had higher odds of being accurate (odds ratio [OR] 1.38 [1.03‐1.84], P = 0.031). In addition, imaging done less than 90 days before transplant had higher odds of being accurate (OR 1.49 [1.06‐2.08], P = 0.019) as did RS = 2 or 3 (OR 5.56 [2.70‐11.11], P < 0.0001). We observed considerable variation in RS accuracy among the United Network for Organ Sharing and Organ Procurement and Transplantation Network regions that is unexplained. In conclusion, current imaging requirements for RS prior to liver transplantation are unacceptably inaccurate. Future policy should require more accurate modalities or combinations of techniques. Liver Transpl 12:1504‐1511, 2006.

Morbid obesity is an independent determinant of death among surgical critically ill patients.

Objective:To determine whether extreme obesity (morbid obesity; body mass index ≥40 kg/m2) is an independent risk factor for death among critically ill patients; this objective is most salient in the subset of patients who sustain a prolonged intensive care unit stay during which the burdens of care imposed by obesity and its consequences would become most apparent. Design:Cohort analysis of data from the Project Impact database used to catalog admissions and outcomes to a surgical intensive care unit, with predetermined end point analyses of outcomes. Setting:Surgical intensive care unit serving Tufts-New England Medical Center, a tertiary care and university medical center in Boston. Patients:All critically ill surgical patients admitted to the Tufts-New England Medical Center surgical intensive care unit from January 1998 to March 2001. Interventions:Intensive care unit and hospital mortality and lengths of stay were compared with body mass index subclassified into five groups: underweight, normal weight, overweight, obese, and extremely obese. Data were examined for all admissions during the study period and for a predetermined subgroup with a prolonged intensive care unit stay (≥4 days). Measurements and Main Results:The prevalence of obesity in the surgical intensive care unit was 26.7%; extreme obesity was observed in 6.8%. In the full cohort of patients (n = 1373), median length of stay was short (2 days) and there were no differences in mortality in patients among any of the body mass index classes. In the subgroup of prolonged stay patients (n = 406), intensive care unit and hospital mortality rates were significantly increased in extremely obese patients compared with all other patients (intensive care unit, 33.3% vs. 12.3%, p = .009; hospital, 33.3% vs. 16%, p = .045). Multivariate analysis showed that extreme obesity was an independent predictor of death in surgical critically ill patients with prolonged intensive care unit stay after controlling for age, gender, and severity of illness. The odds of death increased 7.4 times in patients with morbid obesity. Conclusions:Morbid obesity (body mass index ≥40 kg/m2) is an independent risk factor for death in surgical patients with catastrophic illness requiring prolonged intensive care. The prevalence of obesity is growing, both in the intensive care unit and in the general population. The increased risk of complications and death in this population mandates that we adapt customized processes of care to specifically address this unique and very challenging subset of patients.

Anemia: A Continuing Problem Following Kidney Transplantation

Cardiovascular disease is a leading cause of death among kidney transplant recipients. Anemia, a risk factor for cardiovascular complications among patients with chronic kidney disease, has not been well characterized in kidney transplant recipients. We performed a retrospective cohort study of the prevalence of and factors associated with anemia among 240 patients who underwent kidney transplantation at our institution. The mean hematocrit (Hct) rose from 33% at 1 month after transplantation to 40% at 12 months after transplantation. The proportion of patients with Hct < 36% was 76% at transplantation and 21% and 36%, 1 year and 4 years after transplantation, respectively. Six months after transplantation, women had higher likelihood (OR = 3.61) of Hct < 36%, while higher Hct at 3 months (OR = 0.67 for 1% higher Hct) and diabetes (OR = 0.14) were associated with a lower likelihood of Hct < 36%. Similar associations were seen 12 months after transplantation. Even among patients with Hct < 30%, only 36% had iron studies, 46% received iron supplementation and 40% received recombinant human erythropoietin. Awareness of factors associated with a lower Hct may prompt better anemia screening and management, potentially improving cardiovascular outcomes among kidney transplant recipients.