Hands-Only Cardiopulmonary Resuscitation Education: A Comparison of On-Screen With Compression Feedback, Classroom, and Video Education.

STUDY OBJECTIVE: We compare 3 methods of hands-only cardiopulmonary resuscitation (CPR) education, using performance scores. A paucity of research exists on the comparative effectiveness of different types of hands-only CPR education. This study also includes a novel kiosk approach that has not previously been studied, to our knowledge. METHODS: A randomized, controlled study compared participant scores on 4 hands-only CPR outcome measures after education with a 25- to 45-minute practice-while-watching classroom session (classroom), 4-minute on-screen feedback and practice session (kiosk), and 1-minute video viewing (video only). Participants took a 30-second compression test after initial training and again after 3 months. RESULTS: After the initial education session, the video-only group had a lower total score (compressions correct on hand placement, rate, and depth) (-9.7; 95% confidence interval [CI] -16.5 to -3.0) than the classroom group. There were no significant differences on total score between classroom and kiosk participants. Additional outcome scores help explain which components negatively affect total score for each education method. The video-only group had lower compression depth scores (-9.9; 95% CI -14.0 to -5.7) than the classroom group. The kiosk group outperformed the classroom group on hand position score (4.9; 95% CI 1.3 to 8.6) but scored lower on compression depth score (-5.6; 95% CI -9.5 to -1.8). The change in 4 outcome variables was not significantly different across education type at 3-month follow-up. CONCLUSION: Participants exposed to the kiosk session and those exposed to classroom education performed hands-only CPR similarly, and both groups showed skill performance superior to that of participants watching only a video. With regular retraining to prevent skills decay, the efficient and free hands-only CPR training kiosk has the potential to increase bystander intervention and improve survival from out-of-hospital cardiac arrest.

Clinically Inconsequential Alerts: The Characteristics of Opioid Drug Alerts and Their Utility in Preventing Adverse Drug Events in the Emergency Department.

STUDY OBJECTIVE: We examine the characteristics of clinical decision support alerts triggered when opioids are prescribed, including alert type, override rates, adverse drug events associated with opioids, and preventable adverse drug events. METHODS: This was a retrospective chart review study assessing adverse drug event occurrences for emergency department (ED) visits in a large urban academic medical center using a commercial electronic health record system with clinical decision support. Participants include those aged 18 to 89 years who arrived to the ED every fifth day between September 2012 and January 2013. The main outcome was characteristics of opioid drug alerts, including alert type, override rates, opioid-related adverse drug events, and adverse drug event preventability by clinical decision support. RESULTS: Opioid drug alerts were more likely to be overridden than nonopioid alerts (relative risk 1.35; 95% confidence interval [CI] 1.21 to 1.50). Opioid drug-allergy alerts were twice as likely to be overridden (relative risk 2.24; 95% CI 1.74 to 2.89). Opioid duplicate therapy alerts were 1.57 times as likely to be overridden (95% CI 1.30 to 1.89). Fourteen of 4,581 patients experienced an adverse drug event (0.31%; 95% CI 0.15% to 0.47%), and 8 were due to opioids (57.1%). None of the adverse drug events were preventable by clinical decision support. However, 46 alerts were accepted for 38 patients that averted a potential adverse drug event. Overall, 98.9% of opioid alerts did not result in an actual or averted adverse drug event, and 96.3% of opioid alerts were overridden. CONCLUSION: Overridden opioid alerts did not result in adverse drug events. Clinical decision support successfully prevented adverse drug events at the expense of generating a large volume of inconsequential alerts. To prevent 1 adverse drug event, providers dealt with more than 123 unnecessary alerts. It is essential to refine clinical decision support alerting systems to eliminate inconsequential alerts to prevent alert fatigue and maintain patient safety.

Accuracy of Electronic Medical Record Medication Reconciliation in Emergency Department Patients.

BACKGROUND: Medication history discrepancies have the potential to cause significant adverse clinical effects for patients. More than 40% of medication errors can be traced to inadequate reconciliation. OBJECTIVE: The objective of this study was to determine the accuracy of electronic medical record (EMR)-reconciled medication lists obtained in an academic emergency department (ED). METHODS: Comprehensive research medication ingestion histories for the 48 h preceding ED visit were performed and compared to reconciled EMR medication lists in a convenience sample of ED patients. The reconciled EMR list of prescription, nonprescription, vitamins, herbals, and supplement medications were compared against a structured research medication history tool. We measured the accuracy of the reconciled EMR list vs. the research history for all classes of medications as the primary outcome. RESULTS: Five hundred and two subjects were enrolled. The overall accuracy of EMR-recorded ingestion histories in the preceding 48 h was poor. The EMR was accurate in only 21.9% of cases. Neither age ≥ 65 years (odds ratio [OR] = 1.3; 95% confidence interval [CI] 0.6-2.6) nor sex (female vs. male: OR = 1.5; 95% CI 0.9-2.5) were predictors of accurate EMR history. In the inaccurate EMRs, prescription lists were more likely to include medications that the subject did not report using (78.9%), while the EMR was more likely not to capture nonprescriptions (76.1%), vitamins (73.0%), supplements (67.3%), and herbals (89.1%) that the subject reported using. CONCLUSIONS: Medication ingestion histories procured through triage EMR reconciliation are often inaccurate, and additional strategies are needed to obtain an accurate list.

Survival after amphotericin B overdose treated with plasmapheresis.

OBJECTIVE: To report a case of accidental amphotericin B overdose that was treated with plasmapheresis. CASE SUMMARY: A 60-year-old woman with a history of kidney transplant 4 years prior to presentation for a congenital abnormality was admitted for a suspected systemic fungal infection. The patient inadvertently received intravenous amphotericin B deoxycholate 250 mg (4.3 mg/kg) over 2 hours instead of prescribed liposomal amphotericin B. The medication error was discovered 16 hours after administration. She had normal vital signs at that time and reported abdominal pain and general malaise. Results of a metabolic panel were significant for a creatinine level of 2.1 mg/dL and CO2 of 17 mg/dL. Her serum amphotericin B concentration 33 hours after the initial dose was 4.9 µg/mL. She subsequently received 5 courses of plasmapheresis and 3 courses of hemodialysis and ultimately did not develop any further renal injury, as well as hemolysis, cardiovascular collapse, dysrhythmias, or severe electrolyte abnormalities. DISCUSSION: The dosing differences between nonliposomal and liposomal preparations of amphotericin B can be as high as 50-fold. Reported adverse events from overdose in both animal models and human case reports include renal insufficiency, hemolysis, thrombocytopenia, electrolyte abnormality, and cardiac dysrhythmias. There have been previous reports of similar errors that have led to death. Furthermore, amphotericin B has been shown to be poorly dialyzable. Our patient's serum amphotericin B concentration decreased after she received plasmapheresis, and she did not develop severe complications. CONCLUSIONS: We describe a patient who survived a 4-fold overdose of amphotericin B because of a medication error. The use of plasmapheresis may have enhanced the elimination of amphotericin B and may have contributed to the positive outcome. However, the role of plasmapheresis in amphotericin overdose is not fully understood.

The use of energy drinks, dietary supplements, and prescription medications by United States college students to enhance athletic performance.

While the use of performance enhancing substances by professional, collegiate, and Olympic athletes is well described, the rate of use in the general population is not well studied. We explored the use of energy drinks, dietary supplements, and prescription medications for the enhancement of athletic performance among college students using an ongoing survey system. We conducted a multi-round online questionnaire collecting data from self-identified students at two-year colleges, four-year colleges, online courses, or technical schools at least part-time during the specified sampling period. The sample is obtained through the use of a survey panel company in which respondents voluntarily register. Survey data were collected from December, 2010 through August, 2011. Subjects who reported participating in athletics were asked if they used any of the following substances to enhance athletic performance (1) energy drinks (2) dietary supplements (3) prescription medications within the last year. Data were analyzed from October, 2011 through January, 2012. There were 462 college students who responded to the survey reporting they participate in sports at various levels. Of these, 397 (85.9 %) responded that within the last year they used energy drinks, dietary supplements, or prescription medications to enhance athletic performance. Energy drinks had the highest prevalence (80.1 %), followed by dietary supplements (64.1 %) and prescription medications (53.3 %). Use was most prevalent amongst intercollegiate athletes (89.4 %) followed by club (88.5 %) and intermural (82.1 %) participants. The vast majority of survey respondents reported using energy drinks, dietary supplements, and prescription medications within the last year for athletic performance enhancement.

A Multi-Omic Mosaic Model of Acetaminophen Induced Alanine Aminotransferase Elevation.

BACKGROUND: Acetaminophen (APAP) is the most common cause liver injury following alcohol in US patients. Predicting liver injury and subsequent hepatic regeneration in patients taking therapeutic doses of APAP may be possible using new 'omic methods such as metabolomics and genomics. Multi'omic techniques increase our ability to find new mechanisms of injury and regeneration. METHODS: We used metabolomic and genomic data from a randomized controlled trial of patients administered 4 g of APAP per day for 14 days or longer with blood samples obtained at 0 (baseline), 4, 7, 10, 13 and 16 days. We used the highest ALT as the clinical outcome to be predicted in our integrated analysis. We used penalized regression to model the relationship between genetic variants and day 0 metabolite level, and then performed a metabolite-wide colocalization scan to associate the genetically regulated component of metabolite expression with ALT elevation. Genome-wide association study (GWAS) analyses were conducted for ALT elevation and metabolite level using linear regression, with age, sex, and the first five principal components included as covariates. Colocalization was tested via a weighted sum test. RESULTS: Out of the 164 metabolites modeled, 120 met the criteria for predictive accuracy and were retained for genetic analyses. After genomic examination, eight metabolites were found to be under genetic control and predictive of ALT elevation due to therapeutic acetaminophen. The metabolites were: 3-oxalomalate, allantoate, diphosphate, L-carnitine, L-proline, maltose, and ornithine. These genes are important in the tricarboxylic acid cycle (TCA), urea breakdown pathway, glutathione production, mitochondrial energy production, and maltose metabolism. CONCLUSIONS: This multi'omic approach can be used to integrate metabolomic and genomic data allowing identification of genes that control downstream metabolites. These findings confirm prior work that have identified mitochondrial energy production as critical to APAP induced liver injury and have confirmed our prior work that demonstrate the importance of the urea cycle in therapeutic APAP liver injury.

Management of Acetaminophen Poisoning in the US and Canada: A Consensus Statement.

Importance: The US and Canada currently have no formal published nationwide guidelines for specialists in poison information or emergency departments for the management of acetaminophen poisoning, resulting in significant variability in management. Objective: To develop consensus guidelines for the management of acetaminophen poisoning in the US and Canada. Evidence Review: Four clinical toxicology societies (America's Poison Centers, American Academy of Clinical Toxicology, American College of Medical Toxicology, and Canadian Association of Poison Control Centers) selected participants (n = 21). Led by a nonvoting chairperson using a modified Delphi method, the panel created a decision framework and determined the appropriate clinical management of a patient with acetaminophen poisoning. Unique to this effort was the collection of guidelines from most poison centers in addition to systematic collection and review of the medical literature. Comments from review by external organizations were incorporated before the guideline was finalized. The project began in March 2021 and ended in March 2023. Findings: The search retrieved 84 guidelines and 278 publications. The panel developed guidelines for emergency department management of single or repeated ingestion of acetaminophen. In addition, the panel addressed extended-release formulation, high-risk ingestion, coingestion of anticholinergics or opioids, age younger than 6 years, pregnancy, weight greater than 100 kg, and intravenous acetaminophen use. Differences from current US practice include defining acute ingestion as an ingestion presentation from 4 to 24 hours after overdose was initiated. A revised form of the Rumack-Matthew nomogram was developed. The term massive ingestion was replaced with the term high-risk ingestion and denoted by a specific nomogram line. Other recommendations include specific criteria for emergency department triage, laboratory evaluation and monitoring parameters, defining the role of gastrointestinal decontamination, detailed management of acetylcysteine treatment, associated adverse effects, and stopping criteria for acetylcysteine treatment, as well as criteria for consultation with a clinical toxicologist. Finally, specific treatment considerations, including acetylcysteine dosing, fomepizole administration, and considerations for extracorporeal elimination and transplant evaluation, were addressed. Conclusions and Relevance: This qualitative study provides a consensus statement on consistent evidence-based recommendations for medical, pharmacy, and nursing education and practice to optimize care of patients with acetaminophen poisoning.

Observational studies of patients in the emergency department: a comparison of 4 sampling methods.

STUDY OBJECTIVE: We evaluate the ability of 4 sampling methods to generate representative samples of the emergency department (ED) population. METHODS: We analyzed the electronic records of 21,662 consecutive patient visits at an urban, academic ED. From this population, we simulated different models of study recruitment in the ED by using 2 sample sizes (n=200 and n=400) and 4 sampling methods: true random, random 4-hour time blocks by exact sample size, random 4-hour time blocks by a predetermined number of blocks, and convenience or "business hours." For each method and sample size, we obtained 1,000 samples from the population. Using χ(2) tests, we measured the number of statistically significant differences between the sample and the population for 8 variables (age, sex, race/ethnicity, language, triage acuity, arrival mode, disposition, and payer source). Then, for each variable, method, and sample size, we compared the proportion of the 1,000 samples that differed from the overall ED population to the expected proportion (5%). RESULTS: Only the true random samples represented the population with respect to sex, race/ethnicity, triage acuity, mode of arrival, language, and payer source in at least 95% of the samples. Patient samples obtained using random 4-hour time blocks and business hours sampling systematically differed from the overall ED patient population for several important demographic and clinical variables. However, the magnitude of these differences was not large. CONCLUSION: Common sampling strategies selected for ED-based studies may affect parameter estimates for several representative population variables. However, the potential for bias for these variables appears small.

A characterization of synthetic cannabinoid exposures reported to the National Poison Data System in 2010.

STUDY OBJECTIVE: Δ-9-Tetrahydrocannabinol homologs have been increasingly abused since their introduction in 2004. Such products were used as a "legal high" for those wishing to experience cannabinoid effects while evading basic drugs-of-abuse testing. We describe a series of exposures to products marketed as synthetic cannabinoids to better characterize the clinical effects in these patients. METHODS: All Δ-9-tetrahydrocannabinol homolog exposures reported to the National Poison Data System between January 1, 2010, and October 1, 2010, were extracted with National Poison Data System generic codes and product codes for Δ-9-tetrahydrocannabinol homologs. Only cases involving a single-agent exposure to Δ-9-tetrahydrocannabinol homologs as the major category were analyzed. Descriptive statistics were generated for demographic data, management site, products involved, symptoms, duration of effects, treatments, and severity of clinical effects. RESULTS: During the 9-month study period, there were 1,898 exposures to Δ-9-tetrahydrocannabinol homologs; 1,353 of these cases were single-agent exposures. The mean age was 22.5 years (SD 8.86 years). Most cases were reported in men (n=1,005; 74.3%). The majority of exposures were acute (88.2%; n=1,193). The most common clinical effect was tachycardia (37.7%; n=510). Seizures were reported in 52 patients (3.8%). The majority of clinical effects lasted for fewer than 8 hours (n=711; 78.4%) and resulted in 1,011 non-life-threatening clinical effects (92.9%). The most common therapeutic intervention was intravenous fluids (n=343; 25.3%). There was 1 death (0.1%). CONCLUSION: The majority of cases were in young men intentionally abusing spice. Most exposures resulted in non-life-threatening effects not requiring treatment, although a minority of exposures resulted in more severe effects, including seizures.

Anaphylaxis to black widow spider antivenom.

Black widow spider envenomation is commonly reported to poison centers. Black widow spider envenomation produces a clinical syndrome, known as latrodectism, characterized by headache, nausea, vomiting, several muscle cramping and pain, joint stiffness, hypertension, and regional diaphoresis. Black widow spider antivenom (Merck & Co, Inc, West Point, PA USA) is an effective and relatively safe treatment option. There is 1 clear case of anaphylaxis secondary to black widow spider antivenom reported in the medical literature. Here, we report a case of anaphylaxis to antivenom. A 12-year-old boy presented to the emergency department (ED) with diffuse, severe pain 2 1/2 hours after being bitten by a black widow spider on the right lower extremity. In the ED, the patient failed analgesic therapy with fentanyl and was given black widow spider antivenom. Within 45 minutes, he exhibited signs and symptoms consistent with anaphylaxis, including wheezing, chest tightness, pruritus, and urticarial rash. The patient was given standard therapy for anaphylaxis, and all of his signs and symptoms (including the pain secondary to the black widow envenomation) resolved over 6 hours of observation. Leading experts agree that the use of antivenom is indicated in cases of severe envenomation not responsive to standard therapy. Despite concern that the antivenom is an equine-derived whole IgG and can precipitate early hypersensitivity reactions, there is only 1 other reported case of anaphylaxis to the antivenom in the medical literature.

Genetic variants associated with ALT elevation from therapeutic acetaminophen.

BACKGROUND: Several studies have suggested genetic variants associated with acetaminophen induced liver injury (DILI) following overdose. Genetic variation associated with acetaminophen-induced alanine aminotransferase elevation during therapeutic dosing has not been examined. METHODS: We performed genetic analyses on patients that ingested therapeutic doses of 4 grams of acetaminophen for up to 16 days. We examined 20 genes previously implicated in the metabolism of acetaminophen or the development of immune-mediated DILI using the Illumina Multi-Ethnic Global Array 2. Autosomes were aligned and imputed using TOPMed. A candidate gene region analysis was performed by testing each gene individually using linkage disequilibrium (LD) pruned variants with the adaptive sum of powered scores (aSPU) test from the aSPU R package. The highest measured ALT during therapy, the maximum ALT, was used as the outcome. RESULTS: 192 subjects taking therapeutic APAP were included in the genetic analysis. 136 (70.8%) were female, 133 (69.2%) were Caucasian race, and the median age was 34 years (IQR: 26, 46). Age > 50 years was the only clinical factor associated with maximum ALT increase. Variants in SULT1E1, the gene responsible for Sulfotransferase Family 1E Member 1 enzyme production, were associated with maximum ALT. No single variant drove this association, but rather the association was due to the additive effects of numerous variants within the gene. No other genes were associated with maximum ALT increase in this cohort. CONCLUSION: Acetaminophen induced ALT elevation at therapeutic doses was not associated with variation in most genes associated with acetaminophen metabolism or immune-induced DILI in this cohort. The role of SULT1E1 polymorphism in acetaminophen-induced elevated ALT needs further examination.

Metabolomic markers predictive of hepatic adaptation to therapeutic dosing of acetaminophen.

BACKGROUND: Drug induced liver injury (DILI) remains a prominent global issue and acetaminophen (APAP) overdose represents a common cause of hepatic injury and DILI. Transient alanine aminotransferase (ALT) elevations have been documented while adhering to recommended daily dosing. However, no metabolites have been identified in pre-treatment samples predicting which patients will develop these transient increases. METHODS: This was a secondary analysis of samples collected from a parent study describing the course of ALT levels in subjects receiving therapeutic APAP dosing. Two hundred and four subjects recruited from Denver, Colorado received 4 g APAP/daily for at least 16 days. Subjects were grouped by ALT at any monitored time point above 60 units/L (n = 25) vs. no increase (n = 179). Serum samples from days 0, 7, 16, and 31 were run on ultra-high performance liquid chromatography mass spectrometry. We report the metabolomic results of samples analyzed prior to APAP administration and over time. Significant changes in metabolite and demographic variable expressions were explored using t-tests with false discovery rate correction, chi square, and partial least squares discriminant analyses. RESULTS: Within pre-treatment day 0 samples, allantoate and ornithine were significantly elevated in subjects of the ALT elevation group (p = .032). Baseline ALT (p = .011) and alkaline phosphatase (p = .006) were also significant. These metabolites were significant independent of race, ethnicity, gender, or BMI. CONCLUSIONS: Allantoate and ornithine are directly involved in pathways related to nitrogen release and urea production. Further investigation into alterations in the glutathione metabolism and urea cycle pathways may lead to a greater understanding of the mechanisms associated with hepatic adaptation for a variety of pharmaceuticals.

Acetaminophen-cysteine adducts during therapeutic dosing and following overdose.

BACKGROUND: Acetaminophen-cysteine adducts (APAP-CYS) are a specific biomarker of acetaminophen exposure. APAP-CYS concentrations have been described in the setting of acute overdose, and a concentration >1.1 nmol/ml has been suggested as a marker of hepatic injury from acetaminophen overdose in patients with an ALT >1000 IU/L. However, the concentrations of APAP-CYS during therapeutic dosing, in cases of acetaminophen toxicity from repeated dosing and in cases of hepatic injury from non-acetaminophen hepatotoxins have not been well characterized. The objective of this study is to describe APAP-CYS concentrations in these clinical settings as well as to further characterize the concentrations observed following acetaminophen overdose. METHODS: Samples were collected during three clinical trials in which subjects received 4 g/day of acetaminophen and during an observational study of acetaminophen overdose patients. Trial 1 consisted of non-drinkers who received APAP for 10 days, Trial 2 consisted of moderate drinkers dosed for 10 days and Trial 3 included subjects who chronically abuse alcohol dosed for 5 days. Patients in the observational study were categorized by type of acetaminophen exposure (single or repeated). Serum APAP-CYS was measured using high pressure liquid chromatography with electrochemical detection. RESULTS: Trial 1 included 144 samples from 24 subjects; Trial 2 included 182 samples from 91 subjects and Trial 3 included 200 samples from 40 subjects. In addition, we collected samples from 19 subjects with acute acetaminophen ingestion, 7 subjects with repeated acetaminophen exposure and 4 subjects who ingested another hepatotoxin. The mean (SD) peak APAP-CYS concentrations for the Trials were: Trial 1- 0.4 (0.20) nmol/ml, Trial 2- 0.1 (0.09) nmol/ml and Trial 3- 0.3 (0.12) nmol/ml. APAP-CYS concentrations varied substantially among the patients with acetaminophen toxicity (0.10 to 27.3 nmol/ml). No subject had detectable APAP-CYS following exposure to a non-acetaminophen hepatotoxin. CONCLUSIONS: Lower concentrations of APAP-CYS are detectable after exposure to therapeutic doses of acetaminophen and higher concentrations are detected after acute acetaminophen overdose and in patients with acetaminophen toxicity following repeated exposure.

A US perspective of symptomatic Latrodectus spp. envenomation and treatment: a National Poison Data System review.

BACKGROUND: Black widow spider (Latrodectus spp.) envenomation remains the most clinically significant spider envenomation in the US. The syndrome is characterized by painful muscle rigidity and autonomic disturbances. Treatment has ranged from symptomatic care to administration of specific antivenom. Declining antivenom availability and, possibly, the fear of hypersensitivity allergic reactions, has limited antivenom use in the US. OBJECTIVE: To describe Latrodectus spp. exposures and the subsequent treatment reported to US poison centers; the secondary objective was to identify factors associated with shorter duration of symptoms (<24 hours). METHODS: All Latrodectus spp. exposures reported to the National Poison Data System (NPDS) between January 1, 2000, and December 31, 2008, were reviewed. Cases with at least minor clinical effects due to Latrodectus spp. exposure were extracted. Descriptive statistics were generated. The probability that symptom duration was less than 24 hours was modeled, using logistic regression. RESULTS: From 2000 through 2008, a total of 23,409 Latrodectus spp. exposures were reported in 47 states; 9872 cases had at least minor clinical effects and were included in the subsequent analysis. Exposures peaked in September and fell to a nadir in January and February. Fifty-eight percent of the cases involved males, and the mean (SD) age was 31.5 (17.4) years. Sixty-five percent of the patients had minor clinical effects, 33.5% had moderate effects, 1.4% had major effects, and there were no deaths. Antivenom use was associated with symptom duration of less than 24 hours in moderate and major outcome groups. There was no evidence of shorter symptom duration in patients who received benzodiazepines or calcium. Adverse drug reactions were more common in patients receiving benzodiazepines and antivenom. CONCLUSIONS: In the US, most symptomatic Latrodectus spp. exposures reported to the NPDS are minor. Few patients receive antivenom, although antivenom is associated with shorter symptom duration among moderate and major outcomes.

Dental pain as a risk factor for accidental acetaminophen overdose: a case-control study.

UNLABELLED: Patients frequent take acetaminophen to treat dental pain. One previous study found a high rate of overuse of nonprescription analgesics in an emergency dental clinic. OBJECTIVES: The purpose of this study is to determine if patients with dental pain are more likely to be treated for accidental acetaminophen poisoning than patients with other types of pain. METHODS: We conducted a case-control study at 2 urban hospitals. Cases were identified by chart review of patients who required treatment for accidental acetaminophen poisoning. Controls were self-reported acetaminophen users taking therapeutic doses identified during a survey of emergency department patients. For our primary analysis, the reason for taking acetaminophen was categorized as dental pain or not dental pain. Our primary outcome was the odds ratio of accidental overdose to therapeutic users after adjustment for age, sex, alcoholism, and use of combination products using logistic regression. RESULTS: We identified 73 cases of accidental acetaminophen poisoning and 201 therapeutic users. Fourteen accidental overdose patients and 4 therapeutic users reported using acetaminophen for dental pain. The adjusted odds ratio for accidental overdose due to dental pain compared with other reasons for use was 12.8 (95% confidence interval, 4.2-47.6). CONCLUSIONS: We found that patients with dental pain are at increased risk to accidentally overdose on acetaminophen compared with patients taking acetaminophen for other reasons. Emergency physicians should carefully question patients with dental pain about overuse of analgesics.

The Genomics of Elevated ALT and Adducts in Therapeutic Acetaminophen Treatment: a Pilot Study.

INTRODUCTION: Therapeutic acetaminophen (APAP) ingestion causes asymptomatic drug-induced liver injury in some patients. In most cases, elevations in alanine aminotransferase (ALT) are transient and return to the normal range, even with continued APAP ingestion, though ALT elevation persists in some patients unpredictably. The etiology of this liver injury or adaption is unclear. Our objective was to identify new pharmacogenomic variants associated with elevated ALT or elevated protein adduct concentrations in patients receiving therapeutic acetaminophen. METHODS: We performed genome-wide sequencing analysis on eight patients using leftover blood samples from an observational study that administered four grams of acetaminophen for up to 16 days to all patients. Two patients with ALT elevations > two times the upper limit of normal, two patients with no adduct formation, and four control patients were sequenced. The genomes were aligned with the GRCh38 reference sequence, and variants with predicted low, moderate, or high impact on the subsequent proteins were first manually curated for biologic plausibility, then organized and examined in the REACTOME pathway analysis program. RESULTS: We found 394 variants in 107 genes associated with elevated ALT. Variants associated with ALT elevation predominantly involved genes in the immune system (MHC class II complex genes), endoplasmic reticulum stress response (SEC23B and XBP1), oxidative phosphorylation (NDUFB9), and WNT/beta-catenin signaling (FZD5). Variants associated with elevated adducts were primarily in signal transduction (MUC20) and DNA repair mechanisms (P53). CONCLUSIONS: While underpowered, genetic variants in immune system genes may be associated with drug-induced liver injury at therapeutic doses of acetaminophen.

Case reports describing treatments in the emergency medicine literature: missing and misleading information.

BACKGROUND: Although randomized trials and systematic reviews provide the "best evidence" for guiding medical practice, many emergency medicine journals still publish case reports (CRs). The quality of the reporting in these publications has not been assessed. OBJECTIVES: In this study we sought to determine the proportion of treatment-related case reports that adequately reported information about the patient, disease, interventions, co-interventions, outcomes and other critical information. METHODS: We identified CRs published in 4 emergency medicine journals in 2000-2005 and categorized them according to their purpose (disease description, overdose or adverse drug reactioin, diagnostic test or treatment effect). Treatment-related CRs were reviewed for the presence or absence of 11 reporting elements. RESULTS: All told, 1,316 CRs were identified; of these, 85 (6.5%; 95CI = 66, 84) were about medical or surgical treatments. Most contained adequate descriptions of the patient (99%; 95CI = 95, 100), the stage and severity of the patient's disease (88%; 95CI = 79, 93), the intervention (80%; 95CI = 70, 87) and the outcomes of treatment (90%; 95CI = 82, 95). Fewer CRs reported the patient's co-morbidities (45%; 95CI = 35, 56), concurrent medications (30%; 95CI = 21, 40) or co-interventions (57%; 95CI = 46, 67) or mentioned any possible treatment side-effects (33%; 95CI = 24, 44). Only 37% (95CI = 19, 38) discussed alternative explanations for favorable outcomes. Generalizability of treatment effects to other patients was mentioned in only 29% (95CI = 20, 39). Just 2 CRs (2.3%; 95CI = 1, 8) reported a 'denominator" (number of patients subjected to the same intervention, whether or not successful. CONCLUSION: Treatment-related CRs in emergency medicine journals often omit critical details about treatments, co-interventions, outcomes, generalizability, causality and denominators. As a result, the information may be misleading to providers, and the clinical applications may be detrimental to patient care.

The In Vivo Net Energy Content of Resistant Starch and Its Effect on Macronutrient Oxidation in Healthy Adults.

The in vivo net energy content of resistant starch (RS) has not been measured in humans so it has not been possible to account for the contribution of RS to dietary energy intake. We aimed to determine the in vivo net energy content of RS and examine its effect on macronutrient oxidation. This was a randomized, double-blind cross-over study. Eighteen healthy adults spent 24 h in a whole room indirect calorimeter to measure total energy expenditure (TEE), substrate oxidation, and postprandial metabolites in response to three diets: 1) digestible starch (DS), 2) RS (33% dietary fiber; RS), or 3) RS with high fiber (RSF, 56% fiber). The in vivo net energy content of RS and RSF are 2.74 ± 0.41 and 3.16 ± 0.27 kcal/g, respectively. There was no difference in TEE or protein oxidation between DS, RS, and RSF. However, RS and RSF consumption caused a 32% increase in fat oxidation (p = 0.04) with a concomitant 18% decrease in carbohydrate oxidation (p = 0.03) versus DS. Insulin responses were unaltered after breakfast but lower in RS and RSF after lunch, at equivalent glucose concentrations, indicating improved insulin sensitivity. The average in vivo net energy content of RS is 2.95 kcal/g, regardless of dietary fiber content. RS and RSF consumption increase fat and decrease carbohydrate oxidation with postprandial insulin responses lowered after lunch, suggesting improved insulin sensitivity at subsequent meals.