Robert Silverman

Age-related association of fine particles and ozone with severe acute asthma in New York City

BACKGROUND Ambient fine particles (particular matter <2.5 microm diameter [PM(2.5)]) and ozone exacerbate respiratory conditions including asthma. There is little documentation determining whether children are more vulnerable to the effects of ambient pollution than adults, or whether pollution causes life-threatening episodes requiring intensive care unit (ICU) admission. OBJECTIVE We investigate the relationship between severe asthma morbidity and PM(2.5) and ozone in the warm season, and determine whether there is an age-related susceptibility to pollution. METHODS Daily time-series analysis of 6008 asthma ICU admissions and 69,375 general (non-ICU) asthma admissions in 4 age groups (<6, 6-18, 19-49, and 50+ years) in 74 New York City hospitals for the months April to August from 1999 to 2006. The regression model adjusted for temporal trends, weather, and day of the week. Risks were estimated for interquartile range increases in the a priori exposure time window of the average of 0-day and 1-day lagged pollutants. RESULTS Age was a significant effect modifier for hospitalizations, and children age 6 to 18 years consistently had the highest risk. Among children age 6 to 18 years, there was a 26% (95% CI, 10% to 44%) increased rate of ICU admissions and a 19% increased rate of general hospitalizations (95% CI, 12% to 27%) for each 12-microg/m(3) increase in PM(2.5). For each 22-ppb increase in ozone, there was a 19% (95% CI, 1% to 40%) increased risk for ICU admissions and a 20% (95% CI, 11% to 29%) increased risk for general hospitalizations. CONCLUSION Warm weather patterns of ozone and PM(2.5) disproportionately affect children with asthma and appear responsible for severe attacks that could have been avoided.

A randomized trial of benralizumab, an antiinterleukin 5 receptor α monoclonal antibody, after acute asthma☆ , ☆☆ ,★,★★, ☆☆☆

BACKGROUND Patients with frequent asthma exacerbations resulting in emergency department (ED) visits are at increased risk for future exacerbations. We examined the ability of 1 dose of benralizumab, an investigational antiinterleukin 5 receptor α monoclonal antibody, to reduce recurrence after acute asthma exacerbations. METHODS In this randomized, double-blind, placebo-controlled study, eligible subjects presented to the ED with an asthma exacerbation, had partial response to treatment, and greater than or equal to 1 additional exacerbation within the previous year. Subjects received 1 intravenous infusion of placebo (n = 38) or benralizumab (0.3 mg/kg, n = 36 or 1.0 mg/kg, n = 36) added to outpatient management. The primary outcome was the proportion of subjects with greater than or equal to 1 exacerbation at 12 weeks in placebo vs the combined benralizumab groups. Other outcomes included the time-weighted rate of exacerbations at week 12, adverse events, blood eosinophil counts, asthma symptom changes, and health care resource utilization. RESULTS The proportion of subjects with greater than or equal to 1 asthma exacerbation at 12 weeks was not different between placebo and the combined benralizumab groups (38.9% vs 33.3%; P = .67). However, compared with placebo, benralizumab reduced asthma exacerbation rates by 49% (3.59 vs 1.82; P = .01) and exacerbations resulting in hospitalization by 60% (1.62 vs 0.65; P = .02) in the combined groups. Benralizumab reduced blood eosinophil counts but did not affect other outcomes, while demonstrating an acceptable safety profile. CONCLUSIONS When added to usual care, 1 dose of benralizumab reduced the rate and severity of exacerbations experienced over 12 weeks by subjects who presented to the ED with acute asthma.

Low levels of serum ionized magnesium are found in patients early after stroke which result in rapid elevation in cytosolic free calcium and spasm in cerebral vascular muscle cells

Ninety-eight patients admitted to the emergency rooms of three urban hospitals with a diagnosis of either ischemic stroke or hemorrhagic stroke exhibited early and significant deficits in serum ionized Mg2+ (IMg2+), but not total Mg, as measured with a unique Mg2+-sensitive ion-selective electrode. Twenty-five percent of these stroke patients exhibited >65% reductions in the mean serum IMg2+ found in normal healthy human volunteers or patients admitted for minor bruises, cuts or deep lacerations. The stroke patients also demonstrated significant elevation in the serum ionized Ca2+ (ICa2+)/IMg2+ ratio, a sign of increased vascular tone and cerebrovasospasm. Exposure of primary cultured canine cerebral vascular smooth muscle cells to the low concentrations of IMg2+ found in the stroke patients, e.g. 0.30-0.48 mM, resulted in rapid and marked elevations in cytosolic free calcium ions ([Ca2+]i) as measured with the fluorescent probe, fura-2, and digital image analysis. Coincident with the rise in [Ca2+]i, many of the cerebral vascular cells went into spasm. Reintroduction of normal extracellular Mg2+ ion concentrations failed to either lower the [Ca2+]i overload or reverse the rounding-up of the cerebral vascular cells. These results suggest that changes in Mg2+ metabolism play important roles in stroke syndromes and in the etiology of cerebrovasospasm associated with cerebral hemorrhage.

A prospective multicenter study of factors associated with hospital admission among adults with acute asthma

PURPOSE We sought to determine patient characteristics associated with hospital admission after emergency treatment for asthma, and whether disposition guidelines are followed. SUBJECTS AND METHODS We performed a prospective multicenter cohort study involving 64 emergency departments in the United States and Canada. Consecutive adult patients with asthma exacerbations were interviewed, and their charts were reviewed using standardized protocols. Telephone follow-up at 2 weeks determined relapse. RESULTS Of 1805 patients, 363 (20%; 95% confidence interval [CI]: 18% to 22%) were hospitalized. Among patients with severe exacerbations (final peak flow <50% of predicted), 122 (49%; 95% CI: 43% to 55%) were hospitalized. Admission was associated with final peak flow, female sex, nonwhite race, severity of chronic illness, and severity of exacerbation. Admission predictors were similar regardless of hospital funding, region, or size. Among patients with mild or moderate exacerbations of asthma (peak flow >or=50% predicted), the likelihood of admission was associated significantly with the number of predefined risk factors for death from asthma. Of patients who were discharged from the emergency department, 62 (5%; 95% CI: 4% to 6%) relapsed within 72 hours. Relapse was not associated with final peak flow (P = 0.39). CONCLUSION Associations between patient characteristics and disposition were similar across sites. Despite guidelines to the contrary, half of patients with final peak flow <50% were discharged. After emergency department treatment and discharge, short-term relapse was uncommon among patients with asthma, suggesting that strict peak flow cutoffs may be unnecessary if risk factors in patients with mild or moderate exacerbations are considered.

Age-related seasonal patterns of emergency department visits for acute asthma in an urban environment

STUDY OBJECTIVE Asthma morbidity is greater in younger patients. The reasons are not fully understood, although identifying demographic patterns of seasonality may help determine causes and potential prevention. The objective of this study is to determine the relationship between age and seasonal asthma periodicity in patients presenting to the emergency department (ED). METHODS We conducted a retrospective study of ED visits from 1991 to 2000 in 11 municipal hospitals in New York City, with 911 receiving facilities. There were 673,141 patients who presented to the ED during the study period and had a primary diagnosis of acute asthma. RESULTS Distinct seasonal patterns were observed, with the highest number of visits occurring in the fall and the fewest in the summer. Seasonal fluctuations of ED visits were highest in children aged 13 years or younger (coefficient of variation [CV] 37.8%; 95% confidence interval [CI] 37.5% to 38.1%), with a peak in CV occurring at approximately age 7 years (CV 43.3%; 95% CI 43.0% to 43.6%). Less variability was noted with increasing age, and the population aged 30 years and older appeared to be the least susceptible to seasonal influences (CV 11.7%; 95% CI 11.3% to 12.1%). Although the total number of asthma visits decreased by more than 30% from 1991 to 2000, the CVs for each year remained within a relatively narrow range of 24.2% to 30.5%. CONCLUSION In an urban population, seasonal variability of asthma episodes requiring ED visits are closely linked to age, which may be important in understanding the causes of asthma and developing disease-management strategies for the prevention of asthma episodes.

Seroprevalence of Tetanus Antibodies Among Adults Older Than 65 Years

STUDY OBJECTIVE To define the extent of immunity against tetanus among patients older than 65 years of age by measuring antitetanus antibody levels. METHODS A convenience sample of 129 patients from an urban comprehensive care geriatric center was studied. Serum was obtained and enzyme-linked immunosorbent assay (ELISA) testing performed. Twenty health care providers, aged 25 to 40 years, were tested for comparison. RESULTS In 64 (50%) of 129 study patients, antitetanus antibody levels did not reach protective levels. Fifty-four (59%) of 92 women and 10 (27%) of 37 men did not have adequate titers. All 20 health care workers had protective titers. CONCLUSION Elderly patients are substantially less likely than young individuals to have adequate immunity against tetanus. Emergency physicians must take this into consideration when evaluating tetanus immunization status in injured elderly patients.

Presence of Fever and Leukocytosis in Acute Cholecystitis

STUDY OBJECTIVE To determine the frequency of fever and leukocytosis in patients presenting to the emergency department with acute cholecystitis (AC). METHODS We carried out a retrospective review of charts from 1990 to 1993 at a university-affiliated hospital. Our subjects were ED patients with hepato-iminodiacetic acid (HIDA) scans interpreted as showing AC and who had undergone cholecystectomy during hospitalization. Final diagnosis was determined on the basis of the pathology report. Fever was defined as an oral temperature of 100 degrees F (37.7 degrees C) or greater or a rectal temperature of 100.4 degrees F (38.0 degrees C) or greater. Leukocytosis was defined as a WBC count of 11,000/mm3 or greater. RESULTS Of the 198 cases studied, the pathologic diagnosis of nongangrenous AC was made in 103 (52%), gangrenous AC was diagnosed in 51 (26%), and chronic cholecystitis was diagnosed in 44 (22%). In patients with nongangrenous AC, 71% were afebrile, 32% lacked leukocytosis, and 28% lacked fever and leukocytosis. In patients with gangrenous AC, 59% were afebrile, 27% lacked leukocytosis, and 16% lacked fever and leukocytosis. CONCLUSION We found that patients with AC diagnosed in the ED frequently lacked fever or leukocytosis. The clinician should not rely on the presence of these signs in making the diagnosis of acute cholecystitis.

Association of Ambient Fine Particles With Out-of-Hospital Cardiac Arrests in New York City

Cardiovascular morbidity has been associated with particulate matter (PM) air pollution, although the relation between pollutants and sudden death from cardiac arrest has not been established. This study examined associations between out-of-hospital cardiac arrests and fine PM (of aerodynamic diameter ≤2.5 μm, or PM(2.5)), ozone, nitrogen dioxide, sulfur dioxide, and carbon monoxide in New York City. The authors analyzed 8,216 out-of-hospital cardiac arrests of primary cardiac etiology during the years 2002-2006. Time-series and case-crossover analyses were conducted, controlling for season, day-of-week, same-day, and delayed/apparent temperature. An increased risk of cardiac arrest in time-series (relative risk (RR) = 1.06, 95% confidence interval (CI): 1.02, 1.10) and case-crossover (RR = 1.04, 95% CI: 0.99, 1.08) analysis for a PM(2.5) increase of 10 μg/m³ in the average of 0- and 1-day lags was found. The association was significant in the warm season (RR = 1.09, 95% CI: 1.03, 1.15) but not the cold season (RR = 1.01, 95% CI: 0.95, 1.07). Associations of cardiac arrest with other pollutants were weaker. These findings, consistent with studies implicating acute cardiovascular effects of PM, support a link between PM(2.5) and out-of-hospital cardiac arrests. Since few individuals survive an arrest, air pollution control may help prevent future cardiovascular mortality.

Hemoglobin A1c as a Screen for Previously Undiagnosed Prediabetes and Diabetes in an Acute-Care Setting

OBJECTIVE Hemoglobin A1c (HbA1c) is recommended for identifying diabetes and prediabetes. Because HbA1c does not fluctuate with recent eating or acute illness, it can be measured in a variety of clinical settings. Although outpatient studies identified HbA1c-screening cutoff values for diabetes and prediabetes, HbA1c-screening thresholds have not been determined for acute-care settings. Using follow-up fasting blood glucose (FBG) and the 2-h oral glucose tolerance test (OGTT) as the criterion gold standard, we determined optimal HbA1c-screening cutoffs for undiagnosed dysglycemia in the emergency department setting. RESEARCH DESIGN AND METHODS This was a prospective observational study of adults aged ≥18 years with no known history of hyperglycemia presenting to an emergency department with acute illness. Outpatient FBS and 2-h OGTT were performed after recovery from the acute illness, resulting in diagnostic categorizations of prediabetes, diabetes, and dysglycemia (prediabetes or diabetes). Optimal cutoffs were determined and performance data identified for cut points. RESULTS A total of 618 patients were included, with a mean age of 49.7 (±14.9) years and mean HbA1c of 5.68% (±0.86). On the basis of an OGTT, the prevalence of previously undiagnosed prediabetes and diabetes was 31.9 and 10.5%, respectively. The optimal HbA1c-screening cutoff for prediabetes was 5.7% (area under the curve [AUC] = 0.659, sensitivity = 55%, and specificity = 71%), for dysglycemia 5.8% (AUC = 0.717, sensitivity = 57%, and specificity = 79%), and for diabetes 6.0% (AUC = 0.868, sensitivity = 77%, and specificity = 87%). CONCLUSIONS We identified HbA1c cut points to screen for prediabetes and diabetes in an emergency department adult population. The values coincide with published outpatient study findings and suggest that an emergency department visit provides an opportunity for HbA1c-based dysglycemia screening.

Boerhaave's syndrome presenting with abdominal pain and right hydropneumothorax

This case of Boerhaaves Syndrome had several unusual features including a delayed presentation and right-sided esophageal perforation. The patients initial episode of hematemesis may have been caused by a small mucosal laceration in the area of the Barretts lesion that later ruptured. On the other hand, if initially there was an esophageal rupture, it did not violate the parietal pleura or mediastinum. The overlying pleura remained intact until digested by gastric contents, thereby causing a right-sided hydropneumo thorax and a marked increase in symptoms, which promoted the patient to come to the ED. Because the patient initially appeared stable and had a history of emesis 4 days before presentation, and because an initial chest X-ray interpretation overlooked the right-sided apical pneumothorax, Boerhaaves Syndrome was not considered initially. Aspiration pneumonia, pancreatitis, alcoholic gastritis, or active peptide ulcer disease were in our initial differential. It was only after the repeat chest X-ray, which more obviously showed the pneumothorax, and insertion of the chest tube that the correct diagnosis was made. Had the pneumothorax not been overlooked initially, the diagnosis may have been made earlier. It is apparent from this case and a review of the literature that Boerhaaves Syndrome is an uncommon clinical entity and has varying modes of presentation, making the diagnosis a difficult clinical challenge. Boerhaaves Syndrome should be considered in all ill-appearing patients presenting with the combination of gastrointestinal and respiratory complaints. The single most important test may be the upright chest X-ray. However, if it is normal, and there is a high index of suspicion, esophagograms and or chest CT may be required to demonstrate the lesion. Because survival is directly related to the time to diagnosis and treatment, a high clinical suspicion can decrease the substantial morbidity and mortality associated with Boerhaaves Syndrome.