David W. Johnson

Comparison of the 20-hour intravenous and 72-hour oral acetylcysteine protocols for the treatment of acute acetaminophen poisoning.

STUDY OBJECTIVEnTo compare outcomes after acute acetaminophen poisoning in 2 large cohorts of patients treated with either the 20-hour intravenous or 72-hour oral acetylcysteine protocol.nnnMETHODSnWe conducted a retrospective cohort study with historical control comparing patients treated with one of 2 acetylcysteine regimens. Data for the 20-hour group were obtained from a medical record review of patients on whom the 20-hour intravenous protocol was initiated in Canadian hospitals from 1980 to 2005. The 72-hour group consisted of a historical cohort of patients treated in US hospitals with the 72-hour oral protocol from 1976 to 1985. The primary outcome was hepatotoxicity (aminotransferase levels >1,000 IU/L).nnnRESULTSnOf the 4,048 patients analyzed, 2,086 were in the 20-hour group and 1,962 were in the 72-hour group. The incidence of hepatotoxicity was 13.9% in the 20-hour group and 15.8% in the 72-hour group (-1.9% absolute difference; 95% confidence interval [CI] -4.2 to 0.3). The relative risk of hepatotoxicity was lower in the 20-hour group when acetylcysteine was initiated within 12 hours of ingestion. The relative risk was lower in the 72-hour group when acetylcysteine was initiated later than 18 hours after ingestion. There was no significant risk difference between groups when acetylcysteine treatment was started 12 to 18 hours after ingestion. One patient in the 20-hour group received a liver transplant and died because of acetaminophen toxicity compared with no liver transplants and 3 deaths in the 72-hour group. Anaphylactoid reactions to intravenous acetylcysteine were reported in 148 of 2,086 patients (7.1%; 95% CI 6.1% to 8.3%). This study is limited by comparison of 2 separate data sets from different countries and study years.nnnCONCLUSIONnThe risk of hepatotoxicity differed between the 20-hour and 72-hour protocols according to the time to initiation of acetylcysteine. It favored the 20-hour protocol for patients presenting early and favored the 72-hour protocol for patients presenting late after acute acetaminophen overdose.

The Treatment of Pediatric Gastroenteritis: A Comparative Analysis of Pediatric Emergency Physicians’ Practice Patterns

OBJECTIVESnAcute gastroenteritis is a very common emergency department (ED) diagnosis accounting for greater than 1.5 million outpatient visits and 200,000 hospitalizations annually among children in the United States. Although guidelines exist to assist clinicians, they do not clearly address topics for which evidence is new or limited, including the use of antiemetic agents, probiotics, and intravenous (IV) fluid rehydration regimens. This study sought to describe the ED treatments administered to children with acute gastroenteritis and to compare management between Canadian and U.S. physicians practicing pediatric emergency medicine (PEM).nnnMETHODSnMembers of PEM research networks located in Canada and the United States were invited to participate in a cross-sectional, Internet-based survey. Participants were included if they are attending physicians and provide care to patients <18 years of age in an ED.nnnRESULTSnIn total, 235 of 339 (73%) eligible individuals responded. A total of 103 of 136 Canadian physicians (76%) report initiating oral rehydration therapy (ORT) in children with moderate dehydration, compared with 44 of 94 (47%) of their U.S. colleagues (p<0.001). The latter more often administer antiemetic agents to children with vomiting (67% vs. 45%; p=0.001). American physicians administer larger IV fluid bolus volumes (p<0.001) and over shorter time periods (p=0.001) and repeat the fluid boluses more frequently (p<0.001). Probiotics are routinely recommended by only 35 of 230 respondents (15%).nnnCONCLUSIONSnThe treatment of pediatric gastroenteritis varies by geographic location and differs significantly between Canadian and American PEM physicians. Oral rehydration continues to be underused, particularly in the United States. Probiotic use remains uncommon, while ondansetron administration has become routine. Children frequently receive IV rehydration, with the rate and volume administered being greater in the United States.

When do the aminotransferases rise after acute acetaminophen overdose

Context. Rising aminotransferases (ATs) [either aspartate aminotransferase (AST) or alanine aminotransferase (ALT) are one of the first signs of hepatotoxicity following acetaminophen (APAP)] overdose (OD). However, the timing and speed of such rises are not well characterized, hampering early risk prediction. Objective. To describe the kinetics of AT release in acute APAP OD patients who develop hepatotoxicity despite treatment. Methods. A descriptive study of acute APAP OD patients with peak AT >u20091,000 IU/L taken from the derivation subset of the Canadian Acetaminophen Overdose Study (CAOS), a large, multicenter retrospective cohort of patients hospitalized for APAP poisoning. Results. Of 2,488 hospital admissions for acute APAP OD, 94 met inclusion criteria. Treatment with acetylcysteine, mostly intravenously, was begun in all cases within 24 h of ingestion. The initial AT concentration was already elevated in most patients at presentation [median 211 (IQR 77–511) IU/L obtained at 15.3 (12.1–19.2) h postingestion], and exceeded 100 IU/L in almost all patients within 24 h of ingestion. Serum AT concentrations rose rapidly [doubling time 9.5 h (95% CI: 8.7–10.4 h)], especially in patients who developed AT >u20091,000 IU/L within 48 h of ingestion. Coagulopathy was worse in these patients and in those with an AT >u2009250 IU/L during the first 12 h of treatment with acetylcysteine. Discussion and conclusions. An abnormal and rapidly doubling AT at presentation is more typical in severely poisoned patients, as judged by the effects on clotting. These data suggest that risk prediction instruments may be improved by incorporating both the serum AT concentration at initiation of antidotal therapy and its rate of change. Further studies using such an approach are warranted.

A 4-year review of pediatric mental health emergencies in Alberta

OBJECTIVEnWe sought to determine and compare rates of pediatric mental health presentations and associated costs in emergency departments (EDs) in Alberta.nnnMETHODSnWe examined 16 154 presentations by 12 589 patients (patient age < or = 17 yr) between April 2002 and March 2006 using the Ambulatory Care Classification System, a province-wide database for Alberta. The following variables of interest were extracted: patient demographics, discharge diagnoses, triage level, disposition, recorded costs for ED care, and institutional classification and location (i.e., rural v. urban, pediatric v. general EDs).nnnRESULTSnA 15% increase in pediatric mental health presentations was observed during the study period. Youth aged 13-17 years consistently represented the most common age group for first presentation to the ED (83.3%). Of the 16 154 recorded presentations, 21.4% were related to mood disorders and 32.5% to anxiety disorders. Presentations for substance misuse or abuse were the most prevalent reasons for a mental health-related visit (41.3%). Multiple visits accounted for more than one-third of all presentations. Presentations for mood disorders were more common in patients with multiple compared with single visits (29.3% v. 16.9%), and substance abuse or misuse presentations were more common in patients with single compared with multiple visits (47.4% v. 30.5%). The total direct ED costs for mental health presentations during the study period was Can

A cluster randomized controlled trial comparing three methods of disseminating practice guidelines for children with croup [ISRCTN73394937]

3.5 million.nnnCONCLUSIONnThis study provides comprehensive data on trends of pediatric mental health presentation, and highlights the costs and return presentations in this population. Psychiatric and medical care provided in the ED for pediatric mental health emergencies should be evaluated to determine quality of care and its relationship with return visits and costs.

A New Predictor of Toxicity Following Acetaminophen Overdose Based on Pretreatment Exposure

BackgroundThe optimal management of croup – a common respiratory illness in young children – is well established. In particular, treatment with corticosteroids has been shown to significantly reduce the rate and duration of intubation, hospitalization, and return to care for on-going croup symptoms. Furthermore treatment with a single dose of corticosteroids does not appear to result in any significant adverse outcomes, and yields overall cost-savings for both families and the health care system.However, as has been shown with many other diseases, there is a significant gap between what we know and what we do. The overall aim of this study is to identify, from a societal perspective, the costs and associated benefits of three strategies for implementing a practice guideline that addresses the management of croup.Methods/designsWe propose to use a matched pair cluster trial in 24 Alberta hospitals randomized into three intervention groups. We will use mixed methods to assess outcomes including linkage and analysis of administrative databases obtained from Alberta Health and Wellness, retrospective medical chart audit, and prospective telephone surveys of the parents of children diagnosed to have croup. The intervention strategies to be compared will be mailing of printed educational materials (low intensity intervention), mailing plus a combination of interactive educational meetings, educational outreach visits, and reminders (intermediate intensity intervention), and a combination of mailing, interactive sessions, outreach visits, reminders plus identification of local opinion leaders and establishment of local consensus processes (high intensity intervention). The primary objective is to determine which of the three intervention strategies are most effective at lowering the rate of hospital days per 1,000 disease episodes. Secondary objectives are to determine which of the three dissemination strategies are most effective at increasing the use of therapies of known benefit. An economic analysis will be conducted to determine which of the three intervention strategies will most effectively reduce total societal costs including all health care costs, costs borne by the family, and costs stemming from the strategies for disseminating guidelines.

Multiplying the serum aminotransferase by the acetaminophen concentration to predict toxicity following overdose.

Introduction. Despite extensive clinical experience, no dose-response curve exists for acetaminophen toxicity in man. The absence of accurate toxicodynamics has hampered efforts to optimize patient therapy and to identify risk modifiers following overdose. We set out to parameterize both the degree and duration of pretreatment exposure into a single, continuous measure of exposure, which will serve as the x-axis of an eventual dose-response curve. Methods. The model was constructed from pharmacokinetic first principles, using as inputs the vertical distance above the Rumack-Matthew nomogram line (expressed as the equivalent serum acetaminophen concentration 4 h after ingestion) and the delay to antidote therapy (tNAC). A no-effect dose ([APAP]threshold) and lag time (ti) were assumed. Results. The area under the serum acetaminophen concentration vs. time curve bounded by [APAP]threshold, ti and tNAC represents our proposed time-weighted measure of exposure. We demonstrate that this non-negative area estimates the cellular burden of toxic adducts formed following overdose. This measure is also easily calculated at patient presentation using clinical data and allows for both declining serum acetaminophen concentrations and variable delays to antidote therapy. Discussion. We describe a new, pharmacokinetically based measure of exposure following acute acetaminophen overdose treated with N-acetylcysteine. Using this measure should enhance the analysis of nonexperimental clinical data and permit more accurate characterization of acetaminophen toxicodynamics. Ultimately, this approach may facilitate progress on many of the long-standing controversies regarding acetaminophen toxicity in man.

Understanding implementation processes of clinical pathways and clinical practice guidelines in pediatric contexts: a study protocol

Context. The first available predictors of hepatic injury following acetaminophen (APAP) overdose are the serum APAP and aminotransferases [AT, i.e., aspartate (AST) aminotransferase or alanine (ALT) aminotransferase]. Objective. We describe the initial value, rate of change, and interrelationship between these biomarkers in patients who develop hepatotoxicity despite treatment following acute overdose. A new parameter, the APAP × AT multiplication product, is proposed for early risk stratification. Methods. We conducted a descriptive study of individuals selected from a multicenter retrospective cohort of patients hospitalized for APAP poisoning. We selected those acute APAP overdose patients who subsequently developed ATu2009u2009>u20091,000 IU/L. Rising serum AT values were compared to simultaneously measured (or estimated) falling serum APAP. The APAP × AT was expressed relative to initiation of acetylcysteine therapy and grouped by time to meeting hepatotoxicity criteria. Results. In the 94 cases studied, serum APAP concentrations were still appreciable [median 570 (interquartile range (IQR) 314–983) μmol/L] at the time of the first measured AT [211 (77–511) IU/L at 15.3 (12.1–19.2) h post-ingestion], yielding an initial APAP × AT of 99,000 (52,000–240,000) μmol × IU/L2. Because serum AT rose rapidly (doubling time 9.5 h ) and APAP fell slowly (half-life 4.8 h), the multiplication product remained elevated during the first 12–24 h of antidotal therapy, especially among patients who developed earlier hepatotoxicity (AT > 1,000 IU/L). Discussion and conclusions. The APAP × AT multiplication product, calculated at the time of presentation and after several h of antidotal therapy, holds promise as a new risk predictor following APAP overdose. It requires neither graphical interpretation nor accurate time of ingestion, two limitations to current risk stratification.

Crowding measures associated with the quality of emergency department care: a systematic review.

BackgroundCanada is among the most prosperous nations in the world, yet the health and wellness outcomes of Canadian children are surprisingly poor. There is some evidence to suggest that these poor health outcomes are partly due to clinical practice variation, which can stem from failure to apply the best available research evidence in clinical practice, otherwise known as knowledge translation (KT). Surprisingly, clinical practice variation, even for common acute paediatric conditions, is pervasive. Clinical practice variation results in unnecessary medical treatments, increased suffering, and increased healthcare costs. This study focuses on improving health outcomes for common paediatric acute health concerns by evaluating strategies that improve KT and reduce clinical practice variation.Design/MethodsUsing a multiple case study design, qualitative and quantitative data will be collected from four emergency departments in western Canada. Data sources will include: pre- and post-implementation focus group data from multidisciplinary healthcare professionals; individual interviews with the local champions, KT intervention providers, and unit/site leaders/managers; Alberta Context Tool (ACT) survey data; and aggregated patient outcome data. Qualitative and quantitative data will be systematically triangulated, and matrices will be built to do cross-case comparison. Explanations will be built about the success or lack of success of the clinical practice guidelines (CPG) and clinical pathways (CPs) uptake based upon the cross-case comparisons.SignificanceThis study will generate new knowledge about the potential causal mechanisms and factors which shape implementation. Future studies will track the impact of the CPG/CPs implementation on childrens health outcome, and healthcare costs.

Quality Indicators for High Acuity Pediatric Conditions

OBJECTIVESnDespite the substantial body of literature on emergency department (ED) crowding, to the best of our knowledge, there is no agreement on the measure or measures that should be used to quantify crowding. The objective of this systematic review was to identify existing measures of ED crowding that have been linked to quality of care as defined by the Institute of Medicine (IOM) quality domains (safe, effective, patient-centered, efficient, timely, and equitable).nnnMETHODSnSix major bibliographic databases were searched from January 1980 to January 2012, and hand searches were conducted of relevant journals and conference proceedings. Observational studies (cross-sectional, cohort, and case-control), quality improvement studies, quasi-experimental (e.g., before/after) studies, and randomized controlled trials were considered for inclusion. Studies that did not provide measures of ED crowding were excluded. Studies that did not provide quantitative data on the link between crowding measures and quality of care were also excluded. Two independent reviewers assessed study eligibility, completed data extraction, and assessed study quality using the Newcastle-Ottawa Quality Assessment Scale (NOS) for observational studies and a modified version of the NOS for cross-sectional studies.nnnRESULTSnThe search identified 7,413 articles. Thirty-two articles were included in the review: six cross-sectional, one case-control, 23 cohort, and two retrospective reviews of performance improvement data. Methodologic quality was moderate, with weaknesses in the reporting of study design and methodology. Overall, 15 of the crowding measures studied had quantifiable links to quality of care. The three measures most frequently linked to quality of care were the number of patients in the waiting room, ED occupancy (percentage of overall ED beds filled), and the number of admitted patients in the ED awaiting inpatient beds. None of the articles provided data on the link between crowding measures and the IOM domains reflecting equitable and efficient care.nnnCONCLUSIONSnThe results of this review provide data on the association between ED crowding measures and quality of care. Three simple crowding measures have been linked to quality of care in multiple publications.