Frances S. Shofer

Impact of time to antibiotics on survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency department

Objective:To study the association between time to antibiotic administration and survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency department. Design:Single-center cohort study. Setting:The emergency department of an academic tertiary care center from 2005 through 2006. Patients:Two hundred sixty-one patients undergoing early goal-directed therapy. Interventions:None. Measurements and Main Results:Effects of different time cutoffs from triage to antibiotic administration, qualification for early goal-directed therapy to antibiotic administration, triage to appropriate antibiotic administration, and qualification for early goal-directed therapy to appropriate antibiotic administration on in-hospital mortality were examined. The mean age of the 261 patients was 59 ± 16 yrs; 41% were female. In-hospital mortality was 31%. Median time from triage to antibiotics was 119 mins (interquartile range, 76–192 mins) and from qualification to antibiotics was 42 mins (interquartile range, 0–93 mins). There was no significant association between time from triage or time from qualification for early goal-directed therapy to antibiotics and mortality when assessed at different hourly cutoffs. When analyzed for time from triage to appropriate antibiotics, there was a significant association at the <1 hr (mortality 19.5 vs. 33.2%; odds ratio, 0.30 [95% confidence interval, 0.11–0.83]; p = .02) time cutoff; similarly, for time from qualification for early goal-directed therapy to appropriate antibiotics, a significant association was seen at the ≤1 hr (mortality 25.0 vs. 38.5%; odds ratio, 0.50 [95% confidence interval, 0.27–0.92]; p = .03) time cutoff. Conclusions:Elapsed times from triage and qualification for early goal-directed therapy to administration of appropriate antimicrobials are primary determinants of mortality in patients with severe sepsis and septic shock treated with early goal-directed therapy.

Community Exposure to Perfluorooctanoate: Relationships Between Serum Concentrations and Exposure Sources

Objective: The objective of this study was to determine serum (perfluorooctanoate [PFOA]) in residents near a fluoropolymer production facility: the contributions from air, water, and occupational exposures, personal and dietary habits, and relationships to age and gender. Methods: The authors conducted questionnaire and serum PFOA measurements in a stratified random sample and volunteers residing in locations with the same residential water supply but with higher and lower potential air PFOA exposure. Results: Serum (PFOA) greatly exceeded general population medians. Occupational exposure from production processes using PFOA and residential water had additive effects; no other occupations contributed. Serum (PFOA) depended on the source of residential drinking water, and not potential air exposure. For public water users, the best-fit model included age, tap water drinks per day, servings of home-grown fruit and vegetables, and carbon filter use. Conclusions: Residential water source was the primary determinant of serum (PFOA).

The Association Between Emergency Department Crowding and Adverse Cardiovascular Outcomes in Patients with Chest Pain

OBJECTIVES While emergency department (ED) crowding is a worldwide problem, few studies have demonstrated associations between crowding and outcomes. The authors examined whether ED crowding was associated with adverse cardiovascular outcomes in patients with chest pain syndromes (chest pain or related complaints of possible cardiac origin). METHODS A retrospective analysis was performed for patients >or=30 years of age with chest pain syndrome admitted to a tertiary care academic hospital from 1999 through 2006. The authors compared rates of inpatient adverse outcomes from ED triage to hospital discharge, defined as delayed acute myocardial infarction (AMI), heart failure, hypotension, dysrhythmias, and cardiac arrest, which occurred after ED arrival using five separate crowding measures. RESULTS Among 4,574 patients, 251 (4%) patients developed adverse outcomes after ED arrival; 803 (18%) had documented acute coronary syndrome (ACS), and of those, 273 (34%) had AMI. Compared to less crowded times, ACS patients experienced more adverse outcomes at the highest waiting room census (odds ratio [OR] = 3.7, 95% confidence interval [CI] = 1.3 to 11.0) and patient-hours (OR = 5.2, 95% CI = 2.0 to 13.6) and trended toward more adverse outcomes during time of high ED occupancy (OR = 3.1, 95% CI = 1.0 to 9.3). Adverse outcomes were not significantly more frequent during times with the highest number of admitted patients (OR = 1.6, 95% CI = 0.6 to 4.1) or the highest trailing mean length of stay (LOS) for admitted patients transferred to inpatient beds within 6 hours (OR = 1.5, 95% CI = 0.5 to 4.0). Patients with non-ACS chest pain experienced more adverse outcomes during the highest waiting room census (OR = 3.5, 95% CI = 1.4 to 8.4) and patient-hours (OR = 4.3, 95% CI = 2.6 to 7.3), but not occupancy (OR = 1.8, 95% CI = 0.9 to 3.3), number of admitted patients (OR = 0.6, 95% CI 0.4 to 1.1), or trailing LOS for admitted patients (OR = 1.2, 95% CI = 0.6 to 2.0). CONCLUSIONS There was an association between some measures of ED crowding and a higher risk of adverse cardiovascular outcomes in patients with both ACS-related and non-ACS-related chest pain syndrome.

Coronary Computed Tomographic Angiography for Rapid Discharge of Low-Risk Patients With Potential Acute Coronary Syndromes

STUDY OBJECTIVE Coronary computed tomographic (CT) angiography has excellent performance characteristics relative to coronary angiography and exercise or pharmacologic stress testing. We hypothesize that coronary CT angiography can identify a cohort of emergency department (ED) patients with a potential acute coronary syndrome who can be safely discharged with a less than 1% risk of 30-day cardiovascular death or nonfatal myocardial infarction. METHODS We conducted a prospective cohort study at an urban university hospital ED that enrolled consecutive patients with potential acute coronary syndromes and a low TIMI risk score who presented to the ED with symptoms suggestive of a potential acute coronary syndrome and received a coronary CT angiography. Our intervention was either immediate coronary CT angiography in the ED or after a 9- to 12-hour observation period that included cardiac marker determinations, depending on time of day. The main clinical outcome was 30-day cardiovascular death or nonfatal myocardial infarction. RESULTS Five hundred sixty-eight patients with potential acute coronary syndrome were evaluated: 285 of these received coronary CT angiography immediately in the ED and 283 received coronary CT angiography after a brief observation period. Four hundred seventy-six (84%) were discharged home after coronary CT angiography. During the 30-day follow-up period, no patients died of a cardiovascular event (0%; 95% confidence interval [CI] 0% to 0.8%) or sustained a nonfatal myocardial infarction (0%; 95% CI 0 to 0.8%). CONCLUSION ED patients with symptoms concerning for a potential acute coronary syndrome with a low TIMI risk score and a nonischemic initial ECG result can be safely discharged home after a negative coronary CT angiography test result.

Community Exposure to Perfluorooctanoate: Relationships Between Serum Levels and Certain Health Parameters

Objective: The objective of this study was to determine whether certain biomarkers of toxicity and/or a past diagnosis of liver or thyroid disease were associated with serum perfluorooctanoate concentrations (PFOA) in a community with longstanding environmental exposure to PFOA. Methods: Serum (PFOA), hematologic and biochemical biomarkers, and a questionnaire were administered to 371 residents selected by stratified random sampling and a lottery among volunteers. Median PFOA was 354 ng/mL (interquartile range, 181–571 ng/mL). Results: No significant positive relationships between serum (PFOA) and liver or renal function tests, cholesterol, thyroid-stimulating hormone, or with red cell indices, white cell, or platelet counts. Mean serum (PFOA) was not increased in those with a history of liver or thyroid disease. Conclusions: No toxicity from PFOA was demonstrated using the measured end points; other end points need to be addressed.

Physiologic and antinociceptive effects of intrathecal resiniferatoxin in a canine bone cancer model

Background:Resiniferatoxin is a potent capsaicin analog. Intrathecal administration leads to selective, prolonged opening of the transient receptor potential V1 ion channel, which is localized mainly to C-fiber primary afferent nociceptive sensory neurons. Following work in laboratory animals, the authors explored the use of intrathecal resiniferatoxin to control spontaneous bone cancer pain in companion (pet) dogs. Methods:Normal canine population: Behavioral testing was performed to establish baseline paw withdrawal latency; subsequently, general anesthesia was induced and resiniferatoxin was administered intrathecally while hemodynamic parameters were recorded. Behavior testing was repeated for 12 days after administration of resiniferatoxin. Clinical canine population: Twenty companion dogs with bone cancer pain were recruited. The animal’s baseline level of discomfort and analgesic use were recorded. Resiniferatoxin was administered intrathecally and hemodynamic parameters were monitored while the dogs were under general anesthesia. Dogs were reevaluated up to 14 weeks after resiniferatoxin administration. Results:Normal canine population: In the first minutes after resiniferatoxin injection, there were significant (P < 0.05) increases in mean arterial blood pressure and heart rate from baseline. Two days after injection, limb withdrawal latencies increased to the point of cutoff in the dogs that received at least 1.2 &mgr;g/kg resiniferatoxin. Clinical canine population: From baseline, there were significant (P < 0.05) increases in mean arterial blood pressure and heart rate after resiniferatoxin injection. Comfort scores were significantly improved at 2, 6, 10, and 14 weeks after resiniferatoxin administration (P < 0.0001). There was decreased or discontinued use of supplemental analgesics in 67% of the dogs 2 weeks after resiniferatoxin administration. Conclusions:Intrathecal resiniferatoxin elicits transient hemodynamic effects. In controls, a profound and sustained blockade of thermal stimuli is produced in a dose-dependent fashion. Similar administration in dogs with bone cancer produces a prolonged antinociceptive response.

Screening for skin carriage of methicillin-resistant coagulase-positive staphylococci and Staphylococcus schleiferi in dogs with healthy and inflamed skin

Methicillin resistance rates of 41% for Staphylococcus aureus, 16% for S. intermedius, and 40% for S. schleiferi have recently been reported in canine patients. These were deemed to be reflective of referral and clinician-selection biases, which would imply significantly lower methicillin-resistant staphylococcal carriage rates in less-biased canine populations. In this study, swabs for bacterial culture were collected from five cutaneous sites on each of 50 healthy dogs and 59 dogs with inflammatory skin disease to determine prevalence of carriage and relative frequency of methicillin resistance in coagulase-positive staphylococci and S. schleiferi ssp. schleiferi. These were identified morphologically and by Grams staining, catalase and coagulase testing, and biochemical speciation. Coagulase-positive staphylococci and S. schleiferi ssp. schleiferi were isolated from 88% (52 of 59) of affected dogs. Species identified in the culture-positive dogs were: S. aureus in 12%, S. intermedius (92%), S. schleiferi ssp. schleiferi (10%), and S. schleiferi ssp. coagulans (10%) with methicillin resistance rates of 17%, 8%, 20% and 20%, respectively. Coagulase-positive staphylococci were isolated from 74% (37 of 50) of healthy dogs: S. aureus (16%), S. intermedius (92%) and S. schleiferi ssp. coagulans (5%). Methicillin resistance rates were 0%, 3% and 50%, respectively. Of total methicillin-resistant isolates, 11 of 13 were positive for PBP2a via latex agglutination. Methicillin-resistant S. intermedius and S. schleiferi ssp. schleiferi isolates were all positive for the mecA gene via PCR. There was no significant difference in staphylococcal isolation or methicillin resistance between study groups. While present, methicillin-resistant coagulase-positive staphylococci are significantly less common in these less-biased populations than in the clinical isolates previously reported from this institution which provided the impetus for this study.

Assessment of laryngeal view: Percentage of glottic opening scorevs Cormack and Lehane grading

PurposeTo examine the intra- and inter-rater reliability of two methods that categorize laryngeal view during direct laryngoscopy, the Cormack-Lehane grading system and a new scale, the percentage of glottic opening (POGO) scale.MethodsSeven anesthesiologists from the University of Pennsylvania Health System viewed 25 identical pairs of slides of laryngeal views during direct laryngoscopy. Each anesthesiologist rated the 50 slides for both Cormack-Lehane grades and POGO scores. The latter CL replaces grades 1 and 2 C-L grades with a percentage of glottic opening: the POGO score. Inter and intra-physician reliability for the Cormack-Lehane grades were determined using the kappa statistic analysis, comparison of POGO scores was performed using the intraclass correlation coefficients (r1).ResultsThe POGO score had a better inter and intra-physician reliability than the Cormack-Lehane grading system. The intra-physician reliability for the POGO score was very good with an average interclass r1 value of 0,88. The inter-physician score was good with a r1 of 0.73. The Cormack-Lehane grading system had excellent intraphysician concordance (average kappa = 0.83.) but the inter-physician reliability was poor (kappa = 0.16.)ConclusionThe Cormack-Lehane grading system has very poor inter-physician reliability. The lack of interphysician reliability with Cormack-Lehane grading calls into question the results of previous studies in which different laryngoscopists used this method to assess laryngeal view. The POGO score appears to have good intra and inter-rater reliability. It has several theoretical advantages and may prove to be more useful for research studies in direct laryngoscopy.RésuméObjectifVérifier la fiabilité intra et interobservateur de deux méthodes de classification de la vue du larynx pendant la laryngoscopie directe: le système de cotation de Cormack-Lehane et une nouvelle échelle, le pourcentage d’ouverture glottique (POG).MéthodeSept anesthésiologistes de l’University of Pennsylvania Health System ont visionné 25 paires identiques de diapositives du larynx sous laryngoscopie directe. Chaque anesthésiologiste a coté les 50 diapositives selon les échelons Cormack-Lehane et les scores POG. Cette dernière échelle remplace les rangs 1 et 2 C-L par un pourcentage d’ouverture glottique: le score POG. La fiabilité inter et intraobservateur des rangs Cormack-Lehane a été déterminée par une analyse statistique kappa, la comparaison des scores POG a été réalisée en utilisant des coefficients de corrélation interclasses (r1).RésultatsLe POG a fourni une meilleure fiabilité inter et intraobservateur que le système de cotation Cormack-Lehane. La fiabilité intraobservateur du score POG a été très bonne, la valeur interclasse moyenne r1 étant de 0,88. Le score interobservateur a été bon selon un r1 de 0,73. Le système de Cormack-Lehane a donné une excellente concordance intraobservateur (kappa moyen = 0,83) mais la fiabilité interobservateur a été pauvre (kappa = 0,16).ConclusionLe système de cotation Cormack-Lehane a présenté une très pauvre fiabilité interobservateur. Cette lacune remet en question les résultats d’études antérieures où différents médecins ont utilisé la méthode pour évaluer la vue du larynx. Le score POG semble avoir une bonne fiabilité intra et interévaluateur. Il présente certains avantages théoriques et peut se révéler plus utile lors de recherches en laryngoscopie directe.

One‐year Outcomes Following Coronary Computerized Tomographic Angiography for Evaluation of Emergency Department Patients with Potential Acute Coronary Syndrome

OBJECTIVES Coronary computerized tomographic angiography (CTA) has high correlation with cardiac catheterization and has been shown to be safe and cost-effective when used for rapid evaluation of low-risk chest pain patients from the emergency department (ED). The long-term outcome of patients discharged from the ED with negative coronary CTA has not been well studied. METHODS The authors prospectively evaluated consecutive low- to intermediate-risk patients who received coronary CTA in the ED for evaluation of a potential acute coronary syndrome (ACS). Patients with cocaine use, known cancer, and significant comorbidity reducing life expectancy and those found to have significant disease (stenosis > or = 50% or ejection fraction < 30%) were excluded. Demographics, medical and cardiac history, labs, and electrocardiogram (ECG) results were collected. Patients were followed by telephone contact and record review for 1 year. The main outcome was 1-year cardiovascular death or nonfatal acute myocardial infarction (AMI). RESULTS Of 588 patients who received coronary CTA in the ED, 481 met study criteria. They had a mean (+/-SD) age of 46.1 (+/-8.8) years, 63% were black or African American, and 60% were female. There were 53 patients (11%) rehospitalized and 51 patients (11%) who received further diagnostic testing (stress or catheterization) over the subsequent year. There was one death (0.2%; 95% confidence interval [CI] = 0.01% to 1.15%) with unclear etiology, no AMI (0%; 95% CI = 0 to 0.76%), and no revascularization procedures (0%; 95% CI = 0 to 0.76%) during this time period. CONCLUSIONS Low- to intermediate-risk patients with a Thrombosis In Myocardial Infarction (TIMI) score of 0 to 2 who present to the ED with potential ACS and have a negative coronary CTA have a very low likelihood of cardiovascular events over the ensuing year.

Effect of Spaying and Timing of Spaying on Survival of Dogs with Mammary Carcinoma

The risk of developing mammary gland tumors in dogs is significantly decreased by ovariohysterectomy at an early age. However, previous studies have not found a benefit to ovariohysterectomy concurrent with tumor removal in dogs with established mammary gland tumors, suggesting that the progression of these tumors is independent of continued estrogen stimulation. The purpose of this study was to evaluate the effect of spaying and of the timing of spaying on survival in dogs with mammary gland carcinoma. Signalment, spay status and spay age, tumor characteristics, treatment. survival, and cause of death of 137 dogs with mammary gland carcinoma were analyzed. The dogs were classified into 3 groups according to spay status and spay time: intact dogs, dogs spayed less than 2 years before tumor surgery (SPAY 1), and dogs spayed more than 2 years before their tumor surgery (SPAY 2). Dogs in the SPAY 1 group lived significantly longer than dogs in SPAY 2 and intact dogs (median survival of 755 days, versus 301 and 286 days, respectively, P = .02 and .03). After adjusting for differences between the spay groups with regard to age, histologic differentiation, and vascular invasion, SPAY 1 dogs survived 45% longer compared to dogs that were either intact or in the SPAY 2 group (RR = .55; 95% CI .32-.93; P = .03). This study reveals ovariohysterectomy to be an effective adjunct to tumor removal in dogs with mammary gland carcinoma and that the timing of ovariohysterectomy is important in influencing survival.