Angela M. Mills

Calpain activity in the rat brain after transient forebrain ischemia

Activity of the Ca(2+)-dependent protease calpain is increased in neurons after global and focal brain ischemia, and may contribute to postischemic injury cascades. Understanding the time course and location of calpain activity in the post-ischemic brain is essential to establishing causality and optimizing therapeutic interventions. This study examined the temporal and spatial characteristics of brain calpain activity after transient forebrain ischemia (TFI) in rats. Male Long Evans rats underwent 10 min of normothermic TFI induced by bilateral carotid occlusion with hypovolemic hypotension (MABP 30 mm Hg). Brain calpain activity was examined between 1 and 72 h after reperfusion. Western blot analysis of regional brain homogenates demonstrated a bimodal pattern of calpain-mediated alpha-spectrin degradation in the hippocampus, cortex, and striatum with an initial increase at 1 h followed by a more prominent secondary increase at 36 h after reperfusion. Immunohistochemical analysis revealed that calpain activity was primarily localized to dendritic fields of selectively vulnerable neurons at one hour after reperfusion. Between 24 and 48 h after reperfusion neuronal calpain activity progressed from the dorsal to ventral striatum, medial to lateral CA1 hippocampus, and centripetally expanded from watershed foci in the cerebral cortex. This progression was associated with fragmentation of dendritic processes, calpain activation in the neuronal soma and subsequent neuronal degeneration. These observations demonstrate a clear association between calpain activation and subsequent delayed neuronal death and suggest broad therapeutic window for interventions aimed at preventing delayed intracellular Ca(2+) overload and pathologic calpain activation.

The association between physician risk tolerance and imaging use in abdominal pain

OBJECTIVE We sought to determine the impact of 3 validated scales of physician risk behavior on imaging use in emergency department (ED) patients with abdominal pain. METHODS We performed a prospective cohort study of nonpregnant ED patients with acute, nontraumatic abdominal pain and then administered 3 instruments (a risk-taking subscale of the Jackson Personality Index, the stress from uncertainty scale, and a malpractice fear scale) to attending physicians who had evaluated these patients and made decisions regarding abdominal imaging. Outcomes were the use of abdominal pelvic computed tomography (CT) and any imaging use (CT, ultrasound, or abdominal plain film). Hierarchical logistic regression was used to determine the effect of risk scales on abdominal imaging use. RESULTS Of 838 patients with acute abdominal pain, 487 (58%) received imaging studies; 395 (47%) received an CT, 111 (13%) ultrasound, and 122 (15%) an abdominal plain film. Both CT and any imaging use were lower among the physicians who were least risk-averse as measured by the risk-taking subscale (highest quartiles vs 3 lower quartiles). In adjusted analysis, probability of CT in the least risk-averse group was 35% (95% confidence interval [CI], 28%-44%) compared to 50% (95% CI, 45%-54%) among more risk-averse physicians, and the probability of any imaging was 53% (95% CI, 44%-61%) compared to 64% (95% CI, 61%-68%). Malpractice fear and stress due to uncertainty were not predictive of imaging use. CONCLUSION Self-reported physician risk-taking behavior predicts the use of imaging in ED patients with abdominal pain, whereas malpractice fear and stress due to uncertainty do not.

Overuse of Computed Tomography Pulmonary Angiography in the Evaluation of Patients with Suspected Pulmonary Embolism in the Emergency Department

BACKGROUND Clinical decision rules have been developed and validated for the evaluation of patients presenting with suspected pulmonary embolism (PE) to the emergency department (ED). OBJECTIVES The objective was to assess the percentage of computed tomographic pulmonary angiography (CT-PA) procedures that could have been avoided by use of the Wells score coupled with D-dimer testing (Wells/D-dimer) or pulmonary embolism rule-out criteria (PERC) in ED patients with suspected PE. METHODS The authors conducted a prospective cohort study of adult ED patients undergoing CT-PA for suspected PE. Wells score and PERC were calculated. A research blood sample was obtained for D-dimer testing for subjects who did not undergo testing as part of their ED evaluation. The primary outcome was PE by CT-PA or 90-day follow-up. Secondary outcomes were ED length of stay (LOS) and CT-PA time as defined by time from order to initial radiologist interpretation. RESULTS Of 152 suspected PE subjects available for analysis (mean ± SD age = 46.3 ± 15.6 years, 74% female, 59% black or African American, 11.8% diagnosed with PE), 14 (9.2%) met PERC, none of whom were diagnosed with PE. A low-risk Wells score (≤4) was assigned to 110 (72%) subjects, of whom only 38 (35%) underwent clinical D-dimer testing (elevated in 33/38). Of the 72 subjects with low-risk Wells scores who did not have D-dimers performed in the ED, archived research samples were negative in 16 (22%). All 21 subjects with low-risk Wells scores and negative D-dimers were PE-negative. CT-PA time (median = 160 minutes) accounted for more than half of total ED LOS (median = 295 minutes). CONCLUSIONS In total, 9.2 and 13.8% of CT-PA procedures could have been avoided by use of PERC and Wells/D-dimer, respectively.

Racial disparity in analgesic treatment for ED patients with abdominal or back pain.

OBJECTIVE Research on how race affects access to analgesia in the emergency department (ED) has yielded conflicting results. We assessed whether patient race affects analgesia administration for patients presenting with back or abdominal pain. METHODS This is a retrospective cohort study of adults who presented to 2 urban EDs with back or abdominal pain for a 4-year period. To assess differences in analgesia administration and time to analgesia between races, Fisher exact and Wilcoxon rank sum test were used, respectively. Relative risk regression was used to adjust for potential confounders. RESULTS Of 20,125 patients included (mean age, 42 years; 64% female; 75% black; mean pain score, 7.5), 6218 (31%) had back pain and 13,907 (69%) abdominal pain. Overall, 12,109 patients (60%) received any analgesia and 8475 (42%) received opiates. Comparing nonwhite (77 %) to white patients (23%), nonwhites were more likely to report severe pain (pain score, 9-10) (42% vs 36%; P < .0001) yet less likely to receive any analgesia (59% vs 66%; P < .0001) and less likely to receive an opiate (39% vs 51%; P < .0001). After controlling for age, sex, presenting complaint, triage class, admission, and severe pain, white patients were still 10% more likely to receive opiates (relative risk, 1.10; 95% confidence interval, 1.06-1.13). Of patients who received analgesia, nonwhites waited longer for opiate analgesia (median time, 98 vs 90 minutes; P = .004). CONCLUSIONS After controlling for potential confounders, nonwhite patients who presented to the ED for abdominal or back pain were less likely than whites to receive analgesia and waited longer for their opiate medication.

Transfer status: A risk factor for mortality in patients with necrotizing fasciitis

BACKGROUND Necrotizing fasciitis (NF) is a rapidly progressive disease that requires urgent surgical debridement for survival. Interhospital transfer (IT) may be associated with delay to operation, which could increase mortality. We hypothesized that mortality would be higher in patients undergoing surgical debridement for necrotizing fasciitis after IT compared to Emergency Department (ED) admission. METHODS We performed a retrospective cohort analysis from 2000-2006 using the Nationwide Inpatient Sample. Inclusion criteria were age >18 years, primary diagnosis of NF, and surgical therapy within 72 hours of admission. Logistic regression was used to assess the relationship between admission source, patient and hospital variables, and mortality. RESULTS We identified 9,958 cases over the study period. Patients in the ED group were more likely to be nonwhite and of lower income when compared with patients in the IT group. Unadjusted mortality was higher in the IT group than ED group (15.5% vs 8.7%, P < .001). After adjusting for potential confounders, odds of mortality were still greater in the IT (OR 2.04, CI 95% 1.60-2.59, P < .001). CONCLUSION Interhospital transfer is associated with increased risk of in-hospital mortality after surgical therapy for NF, a finding which persists after controlling for patient and hospital level variables.

Generational influences in academic emergency medicine: Teaching and learning, mentoring, and technology (Part I)

For the first time in history, four generations are working together-traditionalists, baby boomers, generation Xers (Gen Xers), and millennials. Members of each generation carry with them a unique perspective of the world and interact differently with those around them. Through a review of the literature and consensus by modified Delphi methodology of the Society for Academic Emergency Medicine Aging and Generational Issues Task Force, the authors have developed this two-part series to address generational issues present in academic emergency medicine (EM). Understanding generational characteristics and mitigating strategies can help address some common issues encountered in academic EM. Through recognition of the unique characteristics of each of the generations with respect to teaching and learning, mentoring, and technology, academicians have the opportunity to strategically optimize interactions with one another.

Use of Abdominopelvic Computed Tomography in Emergency Departments and Rates of Urgent Diagnoses in Crohn's Disease

BACKGROUND & AIMS In the United States, the use of abdominopelvic computed tomography (APCT) by emergency departments for patients with abdominal pain has increased, despite stable admission rates and diagnosis requiring urgent intervention. We proposed that trends would be similar for patients with Crohns disease (CD). METHODS We conducted a retrospective study of data from 648 adults with CD who presented at 2 emergency departments (2001-2009; 1572 visits). Trends in APCT use were assessed with Spearman correlation coefficient. We compared patient characteristics and APCT findings during 2001-2003 and 2007-2009. RESULTS APCT use increased from 2001 (used for 47% of encounters) to 2009 (used for 78% of encounters; P = .005), whereas admission rates were relatively stable at 68% in 2001 and 71% in 2009 (P = .06). The overall proportion of APCTs with findings of intestinal perforation, obstruction, or abscess was 29.0%; 34.9% of APCTs were associated with urgent diagnoses, including those unrelated to CD. Between 2001-2003 and 2007-2009, the proportions of APCTs that detected intestinal perforation, obstruction, or abscess were similar (30% vs 29%, P = .92), as were the proportions used to detect any diagnosis requiring urgent intervention, including those unrelated to CD (36% vs 34%, P = .91). CONCLUSIONS Despite the increased use of APCT by emergency departments for patients with CD, there were no significant changes in admission rates between the periods of 2001-2003 and 2007-2009. The proportion of APCTs that detected intestinal perforation, obstruction, abscess, or other urgent conditions not related to CD remained high.

Hyperbaric oxygen therapy in necrotizing soft tissue infections

BACKGROUND Surgical debridement and antibiotics are the mainstays of therapy for patients with necrotizing soft tissue infections (NSTIs), but hyperbaric oxygen therapy (HBO) is often used as an adjunctive measure. Despite this, the efficacy of HBO remains unclear. We hypothesized that HBO would have no effect on mortality or amputation rates. METHODS We performed a retrospective analysis of our institutional experience from 2005 to 2009. Inclusion criteria were age > 18 y and discharge diagnosis of NSTI. We abstracted baseline demographics, physiology, laboratory values, and operative course from the medical record. The primary endpoint was in-hospital mortality; the secondary endpoint was extremity amputation rate. We compared baseline variables using Mann-Whitney, chi-square, and Fishers exact test, as appropriate. Significance was set at P < 0.05. RESULTS We identified 80 cases over the study period. The cohort was 54% male (n = 43) and 53% white (n = 43), and had a mean age of 55 ± 16 y. There were no significant differences in demographics, physiology, or comorbidities between groups. In-hospital mortality was not different between groups (16% in the HBO group versus 19% in the non-HBO group; P = 0.77). In patients with extremity NSTI, the amputation rate did not differ significantly between patients who did not receive HBO and those who did (17% versus 25%; P = 0.46). CONCLUSIONS Hyperbaric oxygen therapy does not appear to decrease in-hospital mortality or amputation rate after in patients with NSTI. There may be a role for HBO in treatment of NSTI; nevertheless, consideration of HBO should never delay operative therapy. Further evidence of efficacy is necessary before HBO can be considered the standard of care in NSTI.

The Use of Decision Support to Measure Documented Adherence to a National Imaging Quality Measure

RATIONALE AND OBJECTIVES Present methods for measuring adherence to national imaging quality measures often require a resource-intensive chart review. Computerized decision support systems may allow for automated capture of these data. We sought to determine the feasibility of measuring adherence to a national quality measure (NQM) regarding computed tomography pulmonary angiograms (CTPAs) for pulmonary embolism using measure-targeted clinical decision support and whether the associated increased burden of data captured required by this system would affect the use and yield of CTs. MATERIALS AND METHODS This institutional review board-approved prospective cohort study enrolled patients from September 1, 2009, through November 30, 2011, in the emergency department (ED) of a 776-bed quaternary-care adults-only academic medical center. Our intervention consisted of an NQM-targeted clinical decision support tool for CTPAs, which required mandatory input of the Wells criteria and serum D-dimer level. The primary outcome was the documented adherence to the quality measure prior and subsequent to the intervention, and the secondary outcomes were the use and yield of CTPAs. RESULTS A total of 1209 patients with suspected PE (2.0% of 58,795 ED visits) were imaged by CTPA during the 12-month control period, and 1212 patients were imaged in the 12 months after the quarter during which the intervention was implemented (2.0% of 59,478 ED visits, P = .84). Documented baseline adherence to the NQM was 56.9% based on a structured review of the provider notes. After implementation, documented adherence increased to 75.6% (P < .01). CTPA yield remained unchanged and was 10.4% during the control period and 10.1% after the intervention (P = .88). CONCLUSIONS Implementation of a clinical decision support tool significantly improved documented adherence to an NQM, enabling automated measurement of provider adherence to evidence without the need for resource-intensive chart review. It did not adversely affect the use or yield of CTPAs.

Poor Sensitivity of a Modified Alvarado Score in Adults With Suspected Appendicitis

STUDY OBJECTIVE A clinical decision rule that identifies patients at low risk for appendicitis may reduce the reliance on computed tomography (CT) for diagnosis. We seek to prospectively evaluate the accuracy of a low modified Alvarado score in emergency department (ED) patients with suspected appendicitis and compare the score to clinical judgment. We hypothesize that a low modified Alvarado score will have a sufficiently high sensitivity to rule out acute appendicitis. METHODS We performed a prospective observational study of adult patients with suspected appendicitis at 2 academic urban EDs. A low modified Alvarado score was defined as less than 4. The sensitivity and specificity were calculated with 95% confidence interval (CI) for a low modified Alvarado score, and a final diagnosis of appendicitis was confirmed by CT, laparotomy, or 7-day follow-up. RESULTS Two hundred sixty-one patients were included for analysis (mean age 35 years [range 18 to 89 years], 68% female patients, 52% white). Fifty-three patients (20%) had acute appendicitis. The modified Alvarado score test characteristics demonstrated a sensitivity and specificity of 72% (95% CI 58% to 84%) and 54% (95% CI 47% to 61%), respectively. Unstructured clinical judgment that appendicitis was either the most likely or second most likely diagnosis demonstrated a sensitivity and specificity of 93% (95% CI 82% to 98%) and 33% (95% CI 27% to 40%), respectively. CONCLUSION With a sensitivity of 72%, a low modified Alvarado score is less sensitive than clinical judgment in excluding acute appendicitis.