Farshad Shirazi

Establishing causality of CNS depression in breastfed infants following maternal codeine use.

AbstractBackground: We recently reported on a breastfed infant who succumbed to opioid toxicity following exposure to morphine, the active metabolite of codeine, which was prescribed to his mother who was a cytochrome P450 2D6 (CYP2D6) ultrarapid metabolizer. This report is believed to be the first case of neonatal fatality as a direct result of maternal drug excretion into breast milk and, therefore, it is critical to corroborate the causative relationship between maternal codeine use during breastfeeding and neonatal opioid toxicity with other existing evidence. Objective: To establish whether maternal use of codeine can be a cause of CNS depression in breastfed infants. Study design: A systematic review of the medical literature using several databases was conducted. The Naranjo Adverse Drug Reaction Probability Scale (NADRPS) was used to examine causality. Results: In addition to our case report, three abstracts and two full-length studies reported adverse drug reactions (ADRs) in infants exposed to codeine in breast milk. In total, 35 infants were identified. Specifically, ADRs were described as unexplained episodes of drowsiness, apnea, bradycardia, and cyanosis in suckling infants. Using the NADRPS, codeine was found to be a definite cause of CNS depression in breastfed infants. Conclusion: The use of codeine by breastfeeding mothers can cause adverse CNS events in breastfed infants. Physicians should recognize codeine use during breastfeeding as a cause of CNS depression in infants, and breastfeeding mothers should be educated on these adverse events before receiving codeine.

Lead Toxicity in a 14-Year-Old Female With Retained Bullet Fragments

In the past 3 decades, lead levels in North American children have been declining. Despite the decline in lead exposure, lead toxicity remains a significant childhood environmental health hazard. The usual route of lead exposure is through ingestion, but lead toxicity secondary to retained bullet fragments has been well documented in the adult literature. The diagnosis of lead toxicity is often difficult and delayed secondary to vague and transient symptoms. Recognizing high-risk characteristics of bullet fragments can improve clinician awareness to the possibility of lead toxicity. The primary management of patients with continued lead exposure is to remove the source of exposure. However, in the case of retained bullet fragments, initiation of chelation therapy before surgical removal may be essential in preventing systemic toxicity. We present the case of a 14-year-old female with lead toxicity who presented with an 18-month course of chronic abdominal pain, vomiting, and anorexia 2 years after sustaining a gunshot wound to the right leg. The patient was treated with oral succimer and operative removal of bullet fragments.

Fatal gastrointestinal hemorrhage after a single dose of dabigatran

Introduction. Dabigatran (Pradaxa) is a new oral anticoagulant approved by the Food and Drug Administration (FDA), available internationally and indicated as an alternative to warfarin for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Dabigatran does not require laboratory monitoring and its kinetics allow for a more rapid onset of action with a time to peak concentration of 1.25–1.5 h. We are reporting a fatality resulting from gastrointestinal bleeding after the ingestion of a single dose of dabigatran 150 mg. Case details. A 92-year-old man with a medical history of chronic obstructive pulmonary disease, hypothyroidism, and atrial flutter presented to the emergency department with complaints of weakness and rectal bleeding. He was seen by his Cardiologist the day before and was found to be in new atrial fibrillation. He was prescribed dabigatran 150 mg twice daily for anticoagulation therapy. He took one dose of dabigatran 150 mg at 2200 and woke up the following morning before 0900 with profuse rectal bleeding. The initial vital signs in the emergency department, approximately 11 h after ingestion, were heart rate 72 beats/min, blood pressure 62/30 mmHg, and lab work showed hemoglobin 9.9 g/dL, international normalization ratio (INR) 1.99, blood urea nitrogen (BUN) 66 mg/dL, and creatinine (SCr) 1.4 mg/dL (creatinine clearance (CrCl) 24.2 mL/min). He was resuscitated with intravenous fluids, two units of packed red blood cells, two units of fresh frozen plasma, platelets, and vitamin K 10 mg intravenously. He was also given an unknown dose of erythromycin early in his hospital stay. An actively bleeding gastric ulcer was discovered and treated with local epinephrine injections. Approximately 48 h after his exposure, he received an additional two units of blood to treat his decreasing blood pressure (98/41 mmHg). On day three, his hemoglobin and hematocrit were stable at 10 g/dL and 30%, INR 1.6, he was extubated and off vasoactive medications. Day six of hospitalization, he began having maroon stools, his hemoglobin decreased to 8.1 g/dL and his platelets to 81 × 1000/mcL. On day seven, the hemoglobin decreased to 6.4 mg/dL. Despite aggressive resuscitative efforts and supportive care, he died. Discussion. This case demonstrates the potential of a single dose of dabigatran 150 mg to result in a fatal gastrointestinal hemorrhage. This patient was started on the maximum dose with a CrCl 33.9 mL/min and on admission CrCl 24.2 mL/min, suggesting underlying renal insufficiency.

Comparison of F(ab')2 versus Fab antivenom for pit viper envenomation: A prospective, blinded, multicenter, randomized clinical trial

Abstract Background. Crotalidae Polyvalent Immune Fab (Ovine) has been the only antivenom commercially available in the US since 2007 for treatment of Crotalinae envenomation. Late coagulopathy can occur or recur after clearance of Fab antivenom, often after hospital discharge, lasting in some cases more than 2 weeks. There have been serious, even fatal, bleeding complications associated with recurrence phenomena. Frequent follow-up is required, and additional intervention or hospitalization is often necessary. F(ab’)2 immunoglobulin derivatives have longer plasma half life than do Fab. We hypothesized that F(ab’)2 antivenom would be superior to Fab in the prevention of late coagulopathy following treatment of patients with Crotalinae envenomation. Methods. We conducted a prospective, double-blind, randomized clinical trial, comparing late coagulopathy in snakebitten patients treated with F(ab’)2 with maintenance doses [F(ab’)2/F(ab’)2], or F(ab’)2 with placebo maintenance doses [F(ab’)2/placebo], versus Fab with maintenance doses [Fab/Fab]. The primary efficacy endpoint was coagulopathy (platelet count < 150 K/mm3, fibrinogen level < 150 mg/dL) between end of maintenance dosing and day 8. Results. 121 patients were randomized at 18 clinical sites and received at least one dose of study drug. 114 completed the study. Of these, 11/37 (29.7%) in the Fab/Fab cohort experienced late coagulopathy versus 4/39 (10.3%, p < 0.05) in the F(ab’)2/F(ab’)2 cohort and 2/38 (5.3%, p < 0.05) in the F(ab’)2/placebo cohort. The lowest heterologous protein exposure was with F(ab’)2/placebo. No serious adverse events were related to study drug. In each study arm, one patient experienced an acute serum reaction and one experienced serum sickness. Conclusions. In this study, management of coagulopathic Crotalinae envenomation with longer-half-life F(ab’)2 antivenom, with or without maintenance dosing, reduced the risk of subacute coagulopathy and bleeding following treatment of envenomation.

Epidemiology of severe and fatal rattlesnake bites published in the American Association of Poison Control Centers’ Annual Reports

Introduction. No study has focused on the nationwide epidemiology of severe and fatal rattlesnake bites during the last 25 years. We examined rates and temporal trends of severe and fatal rattlesnake bites across the United States. Our hypothesis was that nationwide annual rates of both severe and fatal outcomes from rattlesnake bites have remained unchanged over time. Methods. This study retrospectively analyzed all human rattlesnake bites published in the Annual Reports of the American Association of Poison Control Centers from 1983 through 2007. Annual rates of severe (major) and fatal rattlesnake bites were calculated using the annual number of major outcomes and fatalities as respective numerators and the total annual number of single rattlesnake bites (exposures) as denominators. Negative binomial and Poisson regressions were used to examine trends of severe and fatal rattlesnake bites over time. Results. Annually, from 1985 to 2007, the incidence rate of major outcomes decreased by 2% per year (incidence rate ratio = 0.980; CI = 0.967–0.993), corresponding to an absolute annual rate decrease of two major outcomes per 1,000 bites per year. Annual rates of fatalities showed no statistically significant change from 1983 through 2007. Conclusion. This is the first study to examine rates and trends of published severe and fatal rattlesnake bites across the United States over the past 25 years. Annual rates of severe rattlesnake bites, derived from the published Annual Reports of the American Association of Poison Control Centers, have significantly decreased over time, whereas rates of fatal rattlesnake bites have remained unchanged.

Efficiency and economic benefits of a payer-based electronic health record in an emergency department

OBJECTIVES The objective was to evaluate the use of a payer-based electronic health record (P-EHR), which is a clinical summary of a patients medical and pharmacy claims history, in an emergency department (ED) on length of stay (LOS) and plan payments. METHODS A large urban ED partnered with the dominant health plan in the region and implemented P-EHR technology in September 2005 for widespread use for health plan members presenting to the ED. A retrospective observational study design was used to evaluate this previously implemented P-EHR. Health plan and electronic hospital data were used to identify 2,288 ED encounters. Encounters with P-EHR use (n = 779) were identified between September 1, 2005, and February 17, 2006; encounters from the same health plan (n = 1,509) between November 1, 2004, and March 31, 2005, were compared. Outcomes were ED LOS and plan payment for the ED encounter. Analyses evaluated the effect of using the P-EHR in the ED setting on study outcomes using multivariate regressions and the nonparametric bootstrap. RESULTS After covariate adjustment, among visits resulting in discharge (ED-only), P-EHR visits were 19 minutes shorter (95% confidence interval [CI] = 5 to 33 minutes) than non-P-EHR visits. Among visits resulting in hospitalization, the P-EHR was associated with an average 77-minute shorter ED LOS (95% CI = 28 to 126 minutes), compared to non-P-EHR visits. The P-EHR was associated with an average of

Epidemiology of the Reported Severity of Copperhead (Agkistrodon contortrix) Snakebite

1,560 (95% CI =

Incremental Effects of Concurrent Pharmacotherapeutic Regimens for Heart Failure on Hospitalizations and Costs

43 to

Predictors of Prolonged Length of Stay and Adverse Events among Older Adults with Behavioral Health-Related Emergency Department Visits: A Systematic Medical Record Review.

2,910) lower total plan expenditures for hospitalized visits. No significant difference in total payments was observed among discharged visits. CONCLUSIONS In the study ED, the P-EHR was associated with a significant reduction in ED LOS overall and was associated with lower plan payments for visits that resulted in hospitalization.

Epidemiology of the reported severity of cottonmouth (Agkistrodon piscivorus) snakebite.

Objective The goal of this study was to analyze trends in the annual rates of reported medical outcomes of US copperhead (Agkistrodon contortrix) snakebites published in the annual reports of the American Association of Poison Control Centers in the course of 26 years. Methods This was a retrospective analysis of medical outcomes for copperhead snakebite victims who developed fatal, major, moderate, minor, or no effects. The annual rates for these medical outcomes were calculated by dividing the annual number of patients in each outcome category by the total annual number of people reported as being bitten by copperheads. Poisson and negative binomial regression were used to examine trends in annual rates. Results From 1983 through 2008, the incidence rate of copperhead snakebites causing no effect significantly decreased by 12.1%/year (incidence rate ratio [IRR] 0.879; 95% confidence interval [CI] 0.848–0.911]. From 1985 through 2008, the incidence rate of minor outcomes significantly decreased by 2.3%/year (IRR 0.977; 95% CI 0.972–0.981), whereas the rate of moderate outcomes significantly increased by 2.8%/year (IRR 1.028; 95% CI 1.024–1.033). The rate of major outcomes did not significantly change. One fatality was reported in 2001. Conclusions Annual rates of copperhead snakebites producing no effects and minor outcomes significantly decreased, those producing moderate outcomes significantly increased, and those producing major outcomes did not significantly change in a 26-year period.