Faculty Bibliography

Levamisole is a pharmaceutical with anthelminthic and immunomodulatory properties that was previously used in both animals and humans to treat inflammatory conditions and cancer. Levamisole has been identified as a cocaine adulterant in the United States since 2003. By 2009, the United States Drug Enforcement Administration (DEA) estimated that 69% of the cocaine seized contained levamisole. The first case reports of complications related to levamisole in cocaine users were published in 2009. The objectives of this article are to review the literature regarding the full spectrum of possible complications related to levamisole use for medical purposes, to review the current scope of levamisole-induced complications in cocaine users and to discuss the pharmacological properties that might explain the motivation behind the large-scale adulteration of cocaine with levamisole. Literature review revealed that significant complications were quickly reported when levamisole was used in inflammatory conditions. By 1976, several cases of leukopenia and agranulocytosis were reported. Recurrence with re-exposure was well described and agranulocytosis spontaneously reversed upon discontinuation of therapy. Vasculitis secondary to levamisole treatment was first reported in 1978 and mostly manifests as leukocytoclastic vasculitis, cutaneous necrotising vasculitis and thrombotic vasculopathy without vasculitis. These findings typically, but not invariably, involve the ear lobes. Discontinuation of levamisole therapy was again a critical part of the treatment. Various neurological side effects were described with levamisole therapy, the most concerning complication being multifocal inflammatory leukoencephalopathy (MIL). Literature review identified 203 unique cases of complications in cocaine users that can be attributed to levamisole adulteration. The two principal complications reported are haematological (140 cases of neutropenia) and dermatological (84 cases). Even though these complications can occur in isolation, many cases displayed both simultaneously. No formal case of leukoencephalopathy in the setting of cocaine use has been reported so far. A striking phenomenon is the apparent high level of recurrence (27.1%) of symptoms in cocaine users after re-exposure to cocaine that is presumably adulterated. The importance of accurately identifying levamisole-induced complications is therefore critical for symptomatic patients as discontinuation of exposure is fundamental and as a correct diagnosis prevents unnecessary and potentially dangerous use of other treatment modalities like powerful immunosuppressive therapy. Literature review suggests that levamisole might have the advantages of enhancing noradrenergic neurotransmission by inhibiting reuptake, by inhibiting MAO and/or COMT, by acting on ganglionic nicotinic receptors and by being partially metabolized into an amphetamine-like compound. It could also increase endogenous opioids and increase dopamine concentration in the cerebral reward pathway. These potential effects make levamisole an interesting choice as a cocaine adulterant. It seems unlikely that levamisole use as a cocaine adulterant will soon reach an end. More information is needed about the diagnosis and treatment of levamisole-induced complications, and the efforts of the medical and public health community is needed to face this challenging problem.

Background: ED treatment of acute opioid withdrawal (OW) is controversial and challenging. Methadone is commonly used for opioid maintenance and detoxification. Although unstudied, it is also used in low dose at our hospital for acute OW. Objectives: This observational study quantifies the subjective and objective effects of intramuscular (IM) methadone in OW. Methods: A convenience sample of adult, Englishspeaking patients who received IM methadone for OW in a large urban public hospital ED were prospectively enrolled and assessed with four parameters: vital signs; the Clinical Opiate Withdrawal Scale (COWS), a validated OW rating system (scores range from 0-47) the Altered Mental Status Scale (AMSS; scores sedation and agitation from )4 to 4); the Withdrawal Symptoms Scale (WSS), a Likert scale (range )2 [severe withdrawal] to +2 [high]). Patients were assessed prior to methadone and at fixed intervals for 2 hours or until discharge. The ordering physician independently assessed OW symptoms using the WSS. Adverse events, oxygen saturation <95%, respiratory rate <12/ min, or CNS depression (AMSS score <=)2) were recorded. A paired Student's t-test was used to calculate significance. Results: Of 77 patients enrolled, 2 did not meet all inclusion criteria. 50 had two or more assessments for comparison. Their average age was 39 (range 21-59), 70% were male, and 74% were in police custody. 38% used methadone alone; 16% heroin alone; 4% oxycodone alone; and the rest used multiple opioids. The average dose of IM methadone was 10.3 mg (range 5- 20 mg); all but 3 patients received 10 mg. The mean COWS score before receiving IM methadone was 11.19 (range 3-23), compared to 4.83 (range 0-20) 30 minutes after methadone (p < 0.001; mean difference = )6.36; 95% CI = )4.57 to )8.15). The mean WSS before and after methadone was )1.54 (range )1 to )2) and )0.755 (range )2 to 2), respectively (p < 0.001; 95% CI = )1.0 to )0.57). The mean physician-assessed WSS was significantly lower than the patient's own assessment by 0.78 (p < 0.001). Adverse events included an asthmatic patient with bronchospasm whose oxygen saturation decreased from 95% to 88% after receiving methadone, a patient whose oxygen saturation decreased from 95% to 93%, and two patients whose AMSS decreased from )1 to )2 (indicating moderate sedation). Conclusion: Low dose IM methadone effectively ameliorates OW with minimal adverse effects

Objective: Warfarin is a high risk medication whose safety can be greatly improved by patient education. This study was designed to evaluate patients' understanding of their warfarin medication instructions and evaluate readability of the FDA's Warfarin Medication Guide. Methods: Qualitative structured interviews were conducted with 50 patients prescribed warfarin within the last year at two hospital-based outpatient clinics. 19 questions were asked to examine (1) patient understanding of specific sections in the medication guide, (2) prior provision of warfarin medication instructions, (3) numeracy issues specific to warfarin, (4) general medication management, and 5) patient recommendations for better ways to present warfarin information. The study was approved by the IRB at both institutions. Patients were given an incentive that included a tote bag, medicine box, medical ID bracelet, and brochures about the Poison Center. Results: Of the 50 patients who were surveyed, 49 responses were included for analysis. There were slightly more female respondents than male (53.1% vs. 46.9% respectively). 70% of the patients were between 36-64 years old and reported taking 1-18 medications daily. Most patients (75%) had received information about warfarin when they were first prescribed the medi- cine, 65% were given written information, and 48% discussed the medication with their doctors. Only 12% of patients spoke with the pharmacist about their warfarin. When asked to identify specific content in the medication guide, 16% had difficulty with information about diet, and 21% were not able to identify when to call their provider. Numeracy analysis showed that 19% had trouble with both dosing and interpretation of their INR. Patients' suggested alternative ways to present warfarin information including more graphics, in-person counseling, DVD instructional videos, and multilingual translations of the warfarin medication guide. Conclusion: About 20% of patients were unable to identify key messages in the !

Although wolf spider venom has been implicated in necrotic arachnidism without acceptably documented verification, limited, prospectively collected data demonstrate a lack of cutaneous necrosis. The infrequent nature of exposure and inherent difficulty in confirming wolf spider bites in humans makes it challenging to study such envenomations. We present the case of a 20 year-old man with confirmed exposure to the wolf spider who developed cutaneous erythema with ulceration following the bite. There was no evidence of skin necrosis. He was treated with aggressive wound care and systemic antibiotics for wound infection, with subsequent resolution of symptoms. This case adds to the limited knowledge regarding wolf spider envenomations and describes the clinical effects and management of wolf spider envenomation.

OBJECTIVES: Oximes such as pralidoxime (2-PAM) are essential antidotes for life-threatening organophosphate poisoning. Unfortunately, oximes are expensive, have limited use, and have short shelf lives. As such, maintaining large stockpiles in preparation for terrorist activity is not always possible. We have demonstrated that atropine is stable well beyond its labeled shelf life and that recently expired 2-PAM was clinically efficacious in a series of poisoned patients. Because 2-PAM is often dosed empirically, clinical improvement does not guarantee pharmacological stability. We therefore chose to analyze the chemical stability of expired 2-PAM. METHODS: Samples of lyophylized 2-PAM were maintained according to the manufacturer's recommendations for 20 years beyond the published shelf life. We studied 2-PAM contained in a MARK I autoinjector that was stored properly for 3 years beyond its expiration date. An Agilent LC/MSD 1100 with diode-array detector and an Agilent Sorbax SB-C-18, 4.6 x 150-mm, 5-mum column were used with the following solvent systems: water with 0.01% trifluoroacetic acid and methanol with 0.01% trifluoroacetic acid. Fresh reagent grade 2-PAM was used as a standard. Results were repeated for consistency. RESULTS: Lyophylized 2-PAM was a white powder that was clear and colorless in solution. Liquid chromatography was identical to the standard and resulted in 2 isolated peaks with identical mass spectra, suggesting that they are stereoisomers. The autoinjector discharged a clear, yellowish solution. In addition to the 2 peaks identified for lyophylized 2-PAM, a small third peak was identified with a mass spectra corresponding to the reported N -methyl pyridinium carboxaldehyde degradation product. CONCLUSIONS: When properly stored, lyophylized 2-PAM appears to be chemically stable well beyond its expiration date. Although the relative amount of degradation product found in solubilized (autoinjector) 2-PAM was small, it is unclear whether this may be toxic and therefore is of concern. Further studies performed with lots of drug stored under varied conditions would be required to fully determine the stability of expired 2-PAM.

BACKGROUND: Although emergency department (ED) discharge is often based on the presumption of continued care, the reported compliance rate with follow-up appointments is low. STUDY OBJECTIVES: The objectives of this study are to identify factors associated with missed follow-up appointments from the ED and to assess the ability of clinicians to predict which patients will follow-up. METHODS: Patients without insurance or an outpatient primary care provider (PCP) were given a follow-up clinic appointment before discharge. Information identifying potential follow-up barriers was collected, and the physician's perception of the likelihood of follow-up was recorded. Patients who missed their appointment were contacted via telephone and were offered a questionnaire and a rescheduled clinic appointment. RESULTS: A total of 125 patients with no PCP were enrolled. Sixty (48%; 95% confidence interval, 39-57) kept their scheduled appointment. Sex, distance from clinic, availability of transportation, or time since last nonemergent physician visit was associated with attendance to the follow-up visit. Clinicians were unable to predict which patients would follow-up. Contact by telephone was made in 48 (74%) of patients who failed to follow-up. Of the 14 patients willing to reschedule, none returned for follow-up. CONCLUSION: Among ED patients who lack a PCP and are given a clinic appointment from the ED, less than half keep the appointment. Moreover, clinicians are unable to predict which patients will follow up. This study highlights the difficulty in maintaining continuity of care in populations who are self-pay or have Medicaid and lack regular providers. This may have implications on discharge planning from the ED.

We describe a case series of emergency department (ED) visits for intoxication related to the use of the caffeinated alcoholic beverage Four Loko. Medical records from the 4-month period July to November 2010 were hand searched for key words such as 'intoxicated,' 'caffeinated,' 'Four Loko,' 'alcohol,' and 'EtOH.' Patients were included if they were younger than 25 years. Eleven cases were included. Eight (72.7%) patients presented during October 2010. The median age was 16.4 years; 90.9% were under the legal drinking age of 21 years. Seven (63.6 %) were male patients. All arrived by emergency medical services (EMS). Four patients (36.3%) were found in high-risk settings, with altered mental status on subway tracks, in public buildings, or parks after dark. Two patients had blood alcohol concentrations greater than 200 mg/dL. Six patients (54.5%) had emesis. Two patients (18.2%) were admitted to hospital, 1 each because of seizures and persistent tachycardia. Patients intoxicated with Four Loko were younger than the legal drinking age, found in high-risk situations, and often admitted to the hospital. Many of these patients used EMS and resources in the ED for alleviation of adverse effects of Four Loko