Jeffrey R. Brubacher

Incidence, severity and preventability of medication-related visits to the emergency department: a prospective study

Background: Medication-related visits to the emergency department are an important but poorly understood phenomenon. We sought to evaluate the frequency, severity and preventability of drug-related visits to the emergency department. Methods: We performed a prospective observational study of randomly selected adults presenting to the emergency department over a 12-week period. Emergency department visits were identified as drug-related on the basis of assessment by a pharmacist research assistant and an emergency physician; discrepancies were adjudicated by 2 independent reviewers. Results: Among the 1017 patients included in the study, the emergency department visit was identified as drug-related for 122 patients (12.0%, 95% confidence interval [CI] 10.1%–14.2%); of these, 83 visits (68.0%, 95% CI 59.0%–76.2%) were deemed preventable. Severity was classified as mild in 15.6% of the 122 cases, moderate in 74.6% and severe in 9.8%. The most common reasons for drug-related visits were adverse drug reactions (39.3%), nonadherence (27.9%) and use of the wrong or suboptimal drug (11.5%). The probability of admission was significantly higher among patients who had a drug-related visit than among those whose visit was not drug-related (OR 2.18, 95% CI 1.46–3.27, p < 0.001), and among those admitted, the median length of stay was longer (8.0 [interquartile range 23.5] v. 5.5 [interquartile range 10.0] days, p = 0.06). Interpretation: More than 1 in 9 emergency department visits are due to drug-related adverse events, a potentially preventable problem in our health care system.

Route Infrastructure and the Risk of Injuries to Bicyclists: A Case-Crossover Study

OBJECTIVES We compared cycling injury risks of 14 route types and other route infrastructure features. METHODS We recruited 690 city residents injured while cycling in Toronto or Vancouver, Canada. A case-crossover design compared route infrastructure at each injury site to that of a randomly selected control site from the same trip. RESULTS Of 14 route types, cycle tracks had the lowest risk (adjusted odds ratio [OR] = 0.11; 95% confidence interval [CI] = 0.02, 0.54), about one ninth the risk of the reference: major streets with parked cars and no bike infrastructure. Risks on major streets were lower without parked cars (adjusted OR = 0.63; 95% CI = 0.41, 0.96) and with bike lanes (adjusted OR = 0.54; 95% CI = 0.29, 1.01). Local streets also had lower risks (adjusted OR = 0.51; 95% CI = 0.31, 0.84). Other infrastructure characteristics were associated with increased risks: streetcar or train tracks (adjusted OR = 3.0; 95% CI = 1.8, 5.1), downhill grades (adjusted OR = 2.3; 95% CI = 1.7, 3.1), and construction (adjusted OR = 1.9; 95% CI = 1.3, 2.9). CONCLUSIONS The lower risks on quiet streets and with bike-specific infrastructure along busy streets support the route-design approach used in many northern European countries. Transportation infrastructure with lower bicycling injury risks merits public health support to reduce injuries and promote cycling.

Diffusion Tensor Imaging Findings Are Not Strongly Associated With Postconcussional Disorder 2 Months Following Mild Traumatic Brain Injury

Objective:To examine the relation between diffusion tensor imaging (DTI) of the corpus callosum and postconcussion symptom reporting following mild traumatic brain injury (MTBI). Participants:Sixty patients with MTBI and 34 patients with orthopedic/soft-tissue injuries (Trauma Controls) prospectively enrolled from consecutive admissions to a level 1 trauma center. Procedure:Diffusion tensor imaging of the corpus callosum was undertaken using a Phillips 3T scanner at 6 to 8 weeks postinjury. Participants also completed a postconcussion symptom checklist. The MTBI group was divided into 2 subgroups based on the International Classification of Diseases, Tenth Revision symptom criteria for postconcussion disorder (PCD): PCD Present (n = 21), PCD Absent (n = 39). Main Outcome Measures:Measures of fractional anisotropy and mean diffusivity for the genu, body, and splenium of the corpus callosum. Participants also completed the British Columbia Post-Concussion Symptom Inventory. Results:The MTBI group reported more postconcussion symptoms than the trauma controls. There were no significant differences between MTBI and trauma control groups on all DTI measures. In the MTBI sample, there were no significant differences on all DTI measures between those who did and did not meet the International Classification of Diseases, Tenth Revision research criteria for postconcussion disorder. Conclusions:These data do not support an association between white matter integrity in the corpus callosum and self-reported postconcussion syndrome 6 to 8 weeks post-MTBI.

Efficacy of digoxin specific Fab fragments (Digibind®) in the treatment of toad venom poisoning

Chan Su, a traditional Chinese medication, and Love Stone, a topical aphrodisiac, are both made from dried venom of the toad bufo bufo gargarizans and contain bufalin, cinobufotalin, cinobufagin, and other cardioactive steroids of the bufadienolide class. Deaths have occurred following ingestion of these products and the clinical course resembles digoxin toxicity. The purpose of this study was to determine the efficacy of digoxin specific Fab fragments in treating Chan Su poisoning. An ethanolic extract was prepared from Chan Su. Digoxin specific Fab fragments were reconstituted in normal saline to a concentration of 80 mg/ml. An approximate LD90 dose was determined in preliminary experiments. Mice were then randomly divided into a treatment group of 15 mice and a control group of 30 mice. The treatment group was pretreated with 20 ml/kg of digoxin specific Fab fragment solution by intraperitoneal injection at t = 0, followed by 10 ml/kg of digoxin specific Fab fragments intraperitoneal at t = 30 min. The control group was pretreated with equal volumes of intraperitoneal normal saline at the same times. Immediately following the 30 min injection, both groups were given the estimated LD90 dose of Chan Su extract by subcutaneous injection. An endpoint of survival at 6 h was chosen after preliminary results showed that all deaths occurred in the first 4 h. All 30 of the control mice had seizures followed by death compared to 11 seizures and 7deaths in the 15 treatment mice. These results were statistically significant by Fishers exact test (p = 0.00003 for mortality and p = 0.009 for seizures). Digoxin specific Fab fragments are effective in the treatment of Chan Su poisoning in mice and may be effective for poisoning by other cardioactive steroids of the bufadienolide class.

Prophylactic hypothermia for traumatic brain injury: a quantitative systematic review

INTRODUCTION During the past 7 years, considerable new evidence has accumulated supporting the use of prophylactic hypothermia for traumatic brain injury (TBI). Studies can be divided into 2 broad categories: studies with protocols for cooling for a short, predetermined period (e.g., 24-48 h), and those that cool for longer periods and/or terminate based on the normalization of intracranial pressure (ICP). There have been no systematic reviews of hypothermia for TBI that include this recent new evidence. METHODS This analysis followed the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions and the QUOROM (quality of reporting of meta-analyses) statement. We developed a comprehensive search strategy to identify all randomized controlled trials (RCTs) comparing therapeutic hypothermia with standard management in TBI patients. We searched Embase, MEDLINE, Web of Science, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, ProceedingsFirst and PapersFirst. Additional relevant articles were identified by hand-searching conference proceedings and bibliographies. All stages of study identification and selection, quality assessment and analysis were conducted according to prospectively defined criteria. Study quality was determined by assessment of each study for the use of allocation concealment and outcome assessment blinding. Studies were divided into 2 a priori-defined subgroups for analysis based on cooling strategy: short term (< or = 48 h), and long term or goal-directed (> 48 h and/or continued until normalization of ICP). Outcomes included mortality and good neurologic outcome (defined as Glasgow Outcome Scale score of 4 or 5). Pooling of primary outcomes was completed using relative risk (RR) and reported with 95% confidence intervals (CIs). RESULTS Of 1709 articles, 12 studies with 1327 participants were selected for quantitative analysis. Eight of these studies cooled according to a long-term or goal-directed strategy, and 4 used a short-term strategy. Summary results demonstrated lower mortality (RR 0.73, 95% CI 0.62-0.85) and more common good neurologic outcome (RR 1.52, 95% CI 1.28-1.80). When only short-term cooling studies were analyzed, neither mortality (RR 0.98, 95% CI 0.75-1.30) nor neurologic outcome (RR 1.31, 95% CI 0.94-1.83) were improved. In 8 studies of long-term or goal-directed cooling, mortality was reduced (RR 0.62, 95% CI 0.51-0.76) and good neurologic outcome was more common (RR 1.68, 95% CI 1.44-1.96). CONCLUSION The best available evidence to date supports the use of early prophylactic mild-to-moderate hypothermia in patients with severe TBI (Glasgow Coma Scale score < or = 8) to decrease mortality and improve rates of good neurologic recovery. This treatment should be commenced as soon as possible after injury (e.g., in the emergency department after computed tomography) regardless of initial ICP, or before ICP is measured. Most studies report using a temperature of 32 degrees -34 degrees C. The maximal benefit occurred with a long-term or goal-directed cooling protocol, in which cooling was continued for at least 72 hours and/or until stable normalization of intracranial pressure for at least 24 hours was achieved. There is large potential for further research on this therapy in prehospital and emergency department settings.

Outcomes of Emergency Department Patients Presenting With Adverse Drug Events

STUDY OBJECTIVE Our objectives are to describe the outcomes of patients presenting to the emergency department (ED) because of an adverse drug event and to compare them with outcomes of patients presenting for other reasons. METHODS This prospective observational study was conducted at Vancouver General Hospital, a 955-bed tertiary care hospital. We prospectively enrolled adults presenting to the ED between March and June 2006, using a systematic sampling algorithm. Pharmacists and physicians independently evaluated patients for adverse drug events. An independent committee reviewed and adjudicated cases in which assessments were discordant or uncertain. Data from the index visit were linked to vital statistics, administrative health services utilization, and cost of care data. RESULTS Of 1,000 patients, 122 (12.2%; 95% confidence interval [CI] 10.3% to 14.4%) presented to the ED because of an adverse drug event. Of these, 48 presented because of an adverse drug reaction (one type of adverse drug event defined as an unintended response that occurred despite use of an appropriate drug dosage). We found no difference in mortality among patients presenting with and without adverse drug reactions (14.6% versus 5.9%; hazard ratio 1.57; 95% CI 0.70 to 3.52). After adjustment, patients with adverse drug events had a higher risk of spending additional days in the hospital per month (6.3% versus 3.4%; odds ratio 1.52; 95% CI 1.43 to 1.62) and higher rate of outpatient health care encounters (1.73 versus 1.22; rate ratio 1.20; 95% CI 1.03 to 1.40). The adjusted median monthly cost of care was 1.90 times higher (Can

Comparing the effects of infrastructure on bicycling injury at intersections and non-intersections using a case–crossover design

325 versus

Phenformin and lactic acidosis: a case report and review

96; 95% CI 1.18 to 3.08). CONCLUSION ED patients presenting with an adverse drug event incurred greater health services utilization and costs during a 6-month follow-up period compared with patients presenting for other reasons.

Salicylism from Topical Salicylates: Review of the Literature

Background This study examined the impact of transportation infrastructure at intersection and non-intersection locations on bicycling injury risk. Methods In Vancouver and Toronto, we studied adult cyclists who were injured and treated at a hospital emergency department. A case–crossover design compared the infrastructure of injury and control sites within each injured bicyclists route. Intersection injury sites (N=210) were compared to randomly selected intersection control sites (N=272). Non-intersection injury sites (N=478) were compared to randomly selected non-intersection control sites (N=801). Results At intersections, the types of routes meeting and the intersection design influenced safety. Intersections of two local streets (no demarcated traffic lanes) had approximately one-fifth the risk (adjusted OR 0.19, 95% CI 0.05 to 0.66) of intersections of two major streets (more than two traffic lanes). Motor vehicle speeds less than 30 km/h also reduced risk (adjusted OR 0.52, 95% CI 0.29 to 0.92). Traffic circles (small roundabouts) on local streets increased the risk of these otherwise safe intersections (adjusted OR 7.98, 95% CI 1.79 to 35.6). At non-intersection locations, very low risks were found for cycle tracks (bike lanes physically separated from motor vehicle traffic; adjusted OR 0.05, 95% CI 0.01 to 0.59) and local streets with diverters that reduce motor vehicle traffic (adjusted OR 0.04, 95% CI 0.003 to 0.60). Downhill grades increased risks at both intersections and non-intersections. Conclusions These results provide guidance for transportation planners and engineers: at local street intersections, traditional stops are safer than traffic circles, and at non-intersections, cycle tracks alongside major streets and traffic diversion from local streets are safer than no bicycle infrastructure.

Cell phone use and traffic crash risk: a culpability analysis

Phenformin was removed from the U.S. market 20 years ago because of a high incidence of lactic acidosis. Unfortunately, this medication is still available from foreign sources. Another biguanide, metformin, was reintroduced to the United States market for the treatment of diabetes. Biguanide-induced lactic acidosis should be included in the differential diagnosis of elevated anion gap metabolic acidosis. We present a case of phenformin-induced lactic acidosis in which we were consulted at the local poison control center. We also review its pathophysiology, presentation, and treatment. A review of the actions of phenformin illustrates the mechanism of pathology that may also occur with metformin. Risk factors for the development of lactic acidosis include renal deficiency, hepatic disease, cardiac disease, and drug interaction such as cimetidine.