Correction to: Anaphylactoid Reactions to Intravenous N-Acetylcysteine during Treatment for Acetaminophen Poisoning.

The original article has been corrected. Table 4 in PDF version of this article has been corrected since the original publication of the article because the first column of numbers (under the heading "Female") in the original PDF version was typeset poorly.

Anaphylactoid Reactions to Intravenous N-Acetylcysteine during Treatment for Acetaminophen Poisoning.

BACKGROUND: Anaphylactoid reactions to intravenous (IV) N-acetylcysteine (NAC) are well-recognized adverse events during treatment for acetaminophen (APAP) poisoning. Uncertainty exists regarding their incidence, severity, risk factors, and management. We sought to determine the incidence, risk factors, and treatment of anaphylactoid reactions to IV NAC in a large, national cohort of patients admitted to hospital for acetaminophen overdose. METHODS: This retrospective medical record review included all patients initiated on the 21-h IV NAC protocol for acetaminophen poisoning in 34 Canadian hospitals between February 1980 and November 2005. The primary outcome was any anaphylactoid reaction, defined as cutaneous (urticaria, pruritus, angioedema) or systemic (hypotension, respiratory symptoms). We examined the incidence, severity and timing of these reactions, and their association with patient and overdose characteristics using multivariable analysis. RESULTS: An anaphylactoid reaction was documented in 528 (8.2%) of 6455 treatment courses, of which 398 (75.4%) were cutaneous. Five hundred four (95.4%) reactions occurred during the first 5 h. Of 403 patients administered any medication for these reactions, 371 (92%) received an antihistamine. Being female (adjusted OR 1.24 [95%CI 1.08, 1.42]) and having taken a single, acute overdose (1.24 [95%CI 1.10, 1.39]) were each associated with more severe reactions, whereas higher serum APAP concentrations were associated with fewer reactions (0.79 [95%CI 0.68, 0.92]). CONCLUSION: Anaphylactoid reactions to the 21-h IV NAC protocol were uncommon and involved primarily cutaneous symptoms. While the protective effects of higher APAP concentrations are of interest in understanding the pathophysiology, none of the associations identified are strong enough to substantially alter the threshold for NAC initiation.

Can a serum acetaminophen concentration obtained less than 4 hours post-ingestion determine which patients do not require treatment with acetylcysteine?

CONTEXT: The interpretation of acetaminophen concentrations obtained prior to 4 hours after an acute, single overdose remains unclear. Patient care decisions in the Emergency Department could be accelerated if such concentrations could reliably exclude the need for treatment. OBJECTIVE: To determine the agreement between a serum acetaminophen concentration obtained less than 4 hours after an acute ingestion and the subsequent 4 + hour concentration, and the predictive accuracy of early concentrations for identifying patients with potentially toxic exposures. METHODS: A secondary analysis of patients admitted for acetaminophen poisoning at one of the 34 hospitals in eight Canadian cities from 1980 to 2005. We examined serum acetaminophen concentrations obtained less than 4 hours post-ingestion, and again 4 or more hours post-ingestion. For the diagnostic accuracy analysis, we specified a cutpoint of 100 µg/mL (662 µmol/L) obtained between 2 and 4 hours and a subsequent 4 to 20 hour acetaminophen concentration above the nomogram treatment line of 150 µg/mL (993 µmol/L). RESULTS: Of 2454 patients identified, 879 (36%) had a subsequent acetaminophen concentration above the nomogram treatment line. The 2-4 hour concentration demonstrated a sensitivity of 0.96 [95% CI; 0.94, 0.97] and a negative likelihood ratio of 0.070 [0.048, 0.10]. Coingested opioids reduced this sensitivity to 0.91 [0.83, 0.95], and antimuscarinics to 0.86 [0.72, 0.94]. Only very low to undetectable acetaminophen concentrations prior to 4 hours reliably excluded a subsequent concentration over the treatment line. CONCLUSIONS: Applying an acetaminophen concentration cutpoint of 100 µg/mL (662 µmol/L) at 2-4 hours after an acute ingestion as a threshold for repeat testing and/or treatment would occasionally miss potentially toxic exposures. Absorption of acetaminophen is only slightly delayed by coingested opioids or antimuscarinics. Our analysis validates the practice of not retesting when the first post-ingestion acetaminophen concentration is below the lower limit of quantification.

Outcomes of Patients With Premature Discontinuation of the 21-h Intravenous N-Acetylcysteine Protocol After Acute Acetaminophen Overdose.

BACKGROUND: The minimum recommended treatment duration for i.v. N-acetylcysteine (NAC) after an acute, single acetaminophen (APAP) overdose is 21 h. Some have questioned whether shorter courses may be sufficient in carefully selected cases. OBJECTIVE: We sought to describe the incidence of hepatotoxicity in a cohort of acute APAP overdose patients who received <21 h of i.v. NAC for any reason. METHODS: We performed a secondary analysis of a large multicenter retrospective cohort of patients hospitalized for APAP poisoning. We selected patients with a potentially toxic serum APAP concentration measured between 4 and 24 h post ingestion, in whom i.v. NAC was initiated but discontinued before completing the full 21-h course. We further characterized outcomes in these patients as a function of two novel risk-prediction tools, the psi (ψ) parameter and APAP × aminotransferase (AT) product. The ψ parameter is an estimate of the cellular burden of injury based on the area under the concentration-time curve before treatment, and calculated with respect to the APAP concentration and time to initiation of NAC. RESULTS: Fifty-nine patients met inclusion criteria. Intravenous NAC was initiated a median of 11.3 h post ingestion and administered for a median of 11.0 h. Hepatotoxicity (aspartate aminotransferase [AST] or alanine aminotransferase [ALT] > 1,000 IU/L) occurred in one patient (1.7%; 95% confidence interval 0.04-9.1), and eight additional patients developed hepatic injury (AST or ALT > 100 IU/L). No fatalities occurred. A multiplication product of APAP and AT (APAP × AT) that falls below 10,000 µmol/L/IU-L, or pretreatment ψ < 5 mmol/L-h suggested a low risk of hepatic injury. CONCLUSIONS: In this retrospective analysis of patients treated with < 21 h of i.v. NAC for acute APAP overdose, the incidence of hepatotoxicity and coagulopathy was low, despite delays to NAC treatment.

The social determinants of child health: variations across health outcomes - a population-based cross-sectional analysis.

BACKGROUND: Disparities in child health outcomes persist despite advances in medical technology and increased global wealth. The social determinants of health approach is useful in explaining the disparities in health. Our objective in this paper is four-fold: (1) to test whether the income relationship (and the related income gradient) is the same across different child health outcomes; (2) to test whether the association between income and child health outcomes persists after controlling for other traditional socioeconomic characteristics of children and their family (education and employment status); (3) to test the role of other potentially mediating variables, namely parental mental health, number of children, and family structure; and (4) to test the interaction between income and education. METHODS: This population-based cross-sectional study used data from the 2003 US National Survey of Children's Health involving 102,353 children aged 0 to 17 years. Using multivariate logistic regression models, the association between household income, education, employment status, parental mental health, number of children, family structure and the following child health outcomes were examined: presence or absence of asthma, headaches/migraine, ear infections, respiratory allergy, food/digestive allergy, or skin allergy. RESULTS: While the associations of some determinants were found to be consistent across different health outcomes, the association of other determinants such as household income depended on the specific outcome. Controlling for other factors, a gradient association persisted between household income and a child having asthma, migraine/severe headaches, or ear infections with children more likely to have the illness if their family is closer to the federal poverty level. Potentially mediating variables, namely parental mental health, number of children, and family structure had consistent associations across health outcomes. CONCLUSION: There appears to be evidence of an income gradient for certain child health outcomes, even after controlling for other traditional measures of socioeconomic status. Our study also found evidence of an association between certain child health outcomes and potential mediating factors.

A titration strategy is needed to manage breakthrough cancer pain effectively: observations from data pooled from three clinical trials.

BACKGROUND: Breakthrough pain is a prevalent and serious problem in patients with cancer. However, it is not known how best to predict the effective dose of breakthrough opioid for any given patient. METHODS: Data were pooled and reanalyzed from three large, randomized clinical trials of the rapidly absorbed oral transmucosal fentanyl citrate lozenges (OTFC) in which patients were carefully titrated to an optimal OTFC dose. The relationships between the optimal OTFC dose, patients' previous opioid dose, 24-hour total opioid, and patient characteristics were explored to determine whether the optimal OTFC dose can be predicted based on pretreatment clinical factors. RESULTS: The cohort included 188 patients within the three trials whose breakthrough pain was effectively managed with OTFC. Prior to entry into the trial, the average breakthrough opioid dose in the 188 patients was 12% of the daily dose of scheduled opioid but strikingly, ranged from 1%-72%. The optimal OTFC dose was poorly correlated with patients' scheduled or previous breakthrough opioid doses. The only clinically meaningful correlation was that the average final OTFC dose significantly decreased with increasing age. Overall, there was enormous interindividual variability in patients' dose requirements for breakthrough pain. CONCLUSIONS: This is the largest study to date of the relationship between clinical variables and the effective dose of OTFC when titrated to effect for breakthrough cancer pain. These results suggest that use of breakthrough medication should routinely be individualized with a titration strategy separate from the around-the-clock medication, according to each patient's response to their breakthrough opioid.

Are Canadian seniors becoming more active? Empirical evidence based on time-use data.

In this study, we examine trends in the patterns of time use of seniors in Canada since the 1980s. In particular, we ask whether today's seniors devote more, or less, time to productive activities than 20 years ago. Our inquiry is motivated by the claims that today's seniors are not engaged in ''active aging.'' This study uses data from a series of time-use surveys carried out in Canada since 1981 to empirically test the validity of this claim. Our results suggest that some shift towards active aging has taken place in Canada since the 1980s; however, this shift involves a complex pattern of reallocation of time that varies by gender and age.