Acetaminophen protein adducts (APAP adducts) were quantified in 157 adolescents and children presenting at eight pediatric hospitals with the chief complaint of APAP overdose. Two of the patients required liver transplantation, whereas all the others recovered spontaneously. Peak APAP adducts correlated with peak hepatic transaminase values, time-to-treatment with N-acetylcysteine (NAC), and risk determination per the Rumack-Matthews nomogram. A population pharmacokinetic analysis (NONMEM) was performed with post hoc empiric Bayesian estimates determined for the elimination rate constants (k e ), elimination half-lives (t ½ ), and maximum concentration of adducts (C max ) of the subjects. The mean (±SD) k e and half-life were 0.486 ± 0.084 days −1 and 1.47 ± 0.30 days, respectively, and the C max was 1.2 (±2.92) nmol/ml serum. The model-derived, predicted NIH Public Access Author ManuscriptClin Pharmacol Ther. Author manuscript; available in PMC 2010 August 27. Published in final edited form as:Clin Pharmacol Ther. 2008 December ; 84(6): 684-690. doi:10.1038/clpt.2008. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript adduct value at 48 h (Adduct 48) correlated with adduct C max , adduct T max , Rumack-Matthews risk determination, peak aspartate aminotransferase (AST), and peak alanine aminotransferase (ALT). The pharmacokinetics and clinical correlates of APAP adducts in pediatric and adolescent patients with APAP overdose support the need for a further examination of the role of APAP adducts as clinically relevant and specific biomarkers of APAP toxicity.Acetaminophen (APAP) overdose is a common cause of pediatric ingestions, 1 and in severe cases it may result in acute liver failure (ALF).2 Recent data have shown that APAP overdose is a major cause of ALF in adults in the United States.3 In adults, APAP accounts for ~50% of cases of ALF,3 , 4 and in children it accounts for ~13% of cases. 2 It is generally recognized that morbidity in children following an APAP overdose is lower than that in adults. 5,6 However, the etiology of ALF is unknown in ~50% of pediatric cases, and it is possible that APAP overdose may be a contributory factor in some of these cases. The development of new biomarkers of drug toxicity may help to facilitate diagnosis and improve the existing knowledge base of the epidemiology of pediatric ALF.The Rumack-Matthews nomogram is widely used in hospital emergency departments to make determinations on the need for treatment with the antidote, N-acetylcysteine (NAC), following an APAP overdose. The nomogram was derived from time-dependent APAP concentration data generated from adults with single, acute ingestions of APAP who presented to medical centers within 24 h of the APAP overdose.7 However, assessing the risk of developing toxicity is difficult in patients who do not meet these criteria. Examples of patient subgroups for which the Rumack-Matthews nomogram is not applicable include patients presenting in the late stages of toxicity (>24 h after the overdo...

Objectives: Screening for hepatitis C virus (HCV) infection in jail provides an opportunity to educate and offer care to a high-risk population. We aimed to (1) estimate the prevalence of HCV infection in jail; (2) describe the demographic characteristics, risk factors, and pre-incarceration health insurance status associated with HCV infection; and (3) examine the implementation of HCV screening in jail. Methods: We conducted a retrospective analysis of an opt-out HCV screening program with HCV RNA confirmation and patient education at the Dallas County Jail from April 1 through November 2, 2017. We extracted data on test results, demographic characteristics, and release destination from electronic medical records. A nurse navigator recorded data on patient self-reported risk factors and pre-incarceration health insurance status. Results: Of 4089 incarcerated persons screened, 708 (17.3%) had a positive HCV antibody result. Of these, 641 (90.5%) had an HCV RNA test ordered; 576 (89.9%) had RNA tests completed, of whom 413 (71.7%) had a positive HCV RNA result. Of these 413, 352 (85.2%) received patient education. Half of HCV RNA-positive incarcerated persons (n = 207, 50.1%) were born outside the birth cohort (1945-1965). Among those with HCV infection, commonly reported risk factors were injection drug use (168 of 352; 47.8%) and tattoos (82 of 352; 23.4%). Most incarcerated persons with HCV infection (284 of 350; 81.1%) did not have health insurance. HCV antibody prevalence was higher among incarcerated persons released to prison (232 of 961; 24.1%) than to outside agencies (38 of 403; 9.4%) or the community (178 of 1026; 17.4%). Conclusions: Screening for HCV with RNA confirmation in jail provides an opportunity for disease education, transmission prevention, and navigation to HCV treatment. Future efforts should examine post-incarceration linkage to care.

BACKGROUND Inter‐individual variability in response and adverse effects to oxycodone in pediatric patients may be due to CYP2D6 enzyme genetic variation. Intermediate or poor metabolizer (IM, PM) genotypes have impaired oxymorphone formation and may have altered response to oxycodone. This study assessed clinical response and presence of adverse events of oxycodone treatment as a function of CYP2D6 genotype. METHODS Randomized double blind prospective clinical trial in a tertiary care emergency department. 66 children (6–18 y) with orthopedic injuries were randomized to single dose oxycodone (0.1, 0.15 or 0.2 mg/kg). DNA was obtained via buccal swab and CYP2D6 genotype determined. Pain was assessed by Faces Pain Scale (FPS) at baseline, and 20, 40 and 60 minutes post‐dose. RESULTS Dose groups were comparable for demographics and baseline FPS scores. Each group had effective analgesia as evidenced by significant reduction of FPS scores from baseline (p < 0.001). No FPS score differences were demonstrated between dose groups at any time point. No significant adverse events occurred. One patient was a PM (mean FPS = 5.5). IM (n=15, FPS = 3.4 ± 2.6) reported lower FPS scores than extensive metabolizers (EM) reported (n=36, FPS = 4.7 ± 3.0). A GEE model accounted for repeated measures, and found the difference between EM and IM was non‐significant (model coefficient 0.88 (‐0.20, 1.97), p = 0.11). CONCLUSION Findings suggest clinical response to oxycodone varies with CYP2D6 genotype but further study is indicated. Clinical Pharmacology & Therapeutics (2005) 79, P18–P18; doi:

Clinical Pharmacology & Therapeutics (1999) 65, 156–156; doi: