Using administrative health data to estimate prevalence and mortality rates of alcohol and other substance-related disorders for surveillance purposes.

INTRODUCTION: Administrative health databases (AHD) are critical to guide health service management and can inform the whole spectrum of substance-related disorders (SRD). This study estimates prevalence and mortality rates of SRD in administrative health databases. METHODS: The Quebec Integrated Chronic Disease Surveillance System consists of linked AHD. Analyses were performed on data of all Quebec residents aged 12 and over and eligible for health-care coverage using the International Classification of Diseases (ninth or tenth revision) for case identification. Mortality rate ratios stratified by causes of death were obtained to calculate an excess of mortality. RESULTS: Since 2001-2002, the annual age-adjusted prevalence rate of diagnosed overall SRD remained stable (8.6 per 1000 in 2017-2018). In any given year, the annual prevalence rate was significantly higher in males; adolescents had the lowest rate, while adults 65 years and older the highest. The annual 2017-2018 rate was 2.1 per 1000 for alcohol-induced disorder, 1.9 for other drug-induced disorder, 0.7 for alcohol intoxication and 0.6 for other drug intoxications. Cumulative rate of any diagnosis related to alcohol was 32 per 1000 females and 53 per 1000 males (2001-2018), and 33 per 1000 females and 49 per 1000 males for any diagnosis related to other drugs. There was an excess of all-cause mortality among individuals with SRD compared to the general population. DISCUSSION AND CONCLUSIONS: AHD can complement epidemiological surveys in monitoring SRD jurisdiction-wide. Surveillance of services utilisation and interventions, coupled with health outcomes like mortality, could be useful in guiding health services planning.

Antipsychotics for the treatment of sympathomimetic toxicity: A systematic review.

OBJECTIVE: Benzodiazepines are often recommended first-line for management of cocaine and amphetamine toxicity while antipsychotic treatment is discouraged due to the potential for lowering seizure threshold, prolonging the QT interval, and decreasing heat dissipation. We performed a systematic review including animal and human studies to elucidate the efficacy and safety of antipsychotics in managing sympathomimetic toxicity specifically evaluating the effect of treatment on mortality, seizures, hyperthermia, and cardiovascular effects. METHODS: We searched MEDLINE, Embase, BIOSIS Previews, Web of Science, Scopus, CENTRAL and gray literature from inception to 31 May 2017 to answer: Can antipsychotics be used safely and effectively to treat cocaine or amphetamine toxicity? Citations were screened by title and abstract. Additional citations were identified with citation tracking. Data were extracted from full-texts. RESULTS: 6539 citations were identified; 250 full-text articles were assessed. Citation tracking identified 2336 citations; 155 full texts were reviewed. Seventy-three papers were included in this review. In 96 subjects with cocaine toxicity treated with an antipsychotic, there were three deaths, two cardiac arrests, two seizures, and one episode of hyperthermia. In 330 subjects with amphetamine toxicity treated with an antipsychotic, there were two episodes of coma and QT prolongation and one episode of each: hypotension, NMS, cardiac arrest, and death. CONCLUSION: This systematic review represents an exhaustive compilation of the available evidence. There is neither a clear benefit of antipsychotics over benzodiazepines nor a definitive signal of harm noted. We encourage clinicians to adapt treatment based on specific circumstances and characteristics of their individual patients.

Levamisole in cocaine: unexpected news from an old acquaintance.

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.

Lipid emulsions in the treatment of acute poisoning: a systematic review of human and animal studies.

OBJECTIVE: To assess the evidence regarding the efficacy and safety of intravenous fat emulsion (IFE) in the management of poisoned patients. METHODS: We performed a systematic review of the literature with no time or language restriction. The electronic databases were searched from their inception until June 1, 2009 (Medline, EMBASE, ISI web of science, Biological abstract, LILACS, ChemIndex, Toxnet, and Proquest). We also examined the references of identified articles and the gray literature. The target interventions eligible for inclusion were administration of any IFE before, during, or after poisoning in human or animals. All types of studies were reviewed. Eligibility for inclusion and study quality scores, based on criteria by Jadad and the STROBE statement, were evaluated by independent investigators. The primary outcome was mortality. Secondary outcomes included neurologic, hemodynamic, and electrocardiographic variables, as well as adverse effects. RESULTS: Of the 938 publications identified by the search strategies, 74 met the inclusion criteria. We identified 23 animal trials, 50 human, and 1 animal case reports. Overall, the quality of evidence was weak and significant heterogeneity prevented data pooling. Available data suggest some benefits of IFE in bupivacaine, verapamil, chlorpromazine, and some tricyclic antidepressants and beta-blockers toxicity. No trial assessed the safety of IFE in the treatment of acute poisoning. CONCLUSION: The evidence for the efficacy of IFE in reducing mortality and improving hemodynamic, electrocardiographic, and neurological parameters in the poisoned patients is solely based on animal studies and human case reports. The safety of IFE has not been established.