Challenges and approaches to estimating mortality attributable to the use of selected illicit drugs

A number of unique challenges are faced when attempting to estimate mortality attributable to illicit drugs. The hidden nature of illicit drug use creates difficulties in quantifying the prevalence of such use; identifying adverse health effects associated with exposure, and calculating the risk of these effects. The use of cohort studies of drug users allows the identification of causes of mortality associated with drug use and the determination of the risk of these causes. This risk estimate can then be used in conjunction with estimates of the prevalence of drug use to, extrapolate the burden of mortality. We identify a number of such studies and present some solutions to the major challenges faced when attempting to estimate the global burden of mortality attributable to illicit drug use. Copyright (C) 2001 S. Karger AG, Basel.

Heroin overdose: causes and consequences

Over the past decade fatal opioid overdose has emerged as a major public health issue internationally. This paper examines the risk factors for overdose from a biomedical perspective. while significant risk factors for opioid overdose fatality are well recognized, the mechanism of fatal overdose remains unclear. Losses of tolerance and concomitant use of alcohol and other CNS depressants clearly play a major role in fatality; howeve, such risk factors do not account for the strong age and gender patterns observed consistently among victims of overdose. There is evidence that systemic disease may be more prevalent in users at greatest risk of overdose. We hypothesize that pulmonary and hepatic dysfunction resulting from such disease may increase susceptibility to both fatal and non-fatal overdose. Sequelae of non-fatal overdose are recognized in the clinical literature but few epidemiological data exist describing the burden of morbidity arising from such sequelae. The potential for overdose to cause persisting morbidity is reviewed.

Heroin-assisted treatment as a response to the public health problem of opiate dependence

Injection drug use (involving the injection of illicit opiates) poses serious public health problems in many countries. Research has indicated that injection drug users are at higher risk for morbidity in the form of HIV/AIDS and Hepatitis B and C, and drug-related mortality, as well as increased criminal activity. Methadone maintenance treatment is the most prominent form of pharmacotherapy treatment for illicit opiate dependence in several countries, and its application varies internationally with respect to treatment regulations and delivery modes. In order to effectively treat those patients who have previously been resistant to methadone maintenance treatment, several countries have been studying and/or considering heroin-assisted treatment as a complementary form of opiate pharmacotherapy treatment. This paper provides an overview of the prevalence of injection drug use and the opiate dependence problem internationally, the current opiate dependence treatment landscape in several countries, and the status of ongoing or planned heroin-assisted treatment trials in Australia, Canada and certain European countries.

The role of legal coercion in the treatment of offenders with alcohol and heroin problems

This article discusses the ethical justification for and reviews the American evidence on the effectiveness of; treatment for alcohol and heroin dependence that is provided under legal coercion to offenders whose alcohol and drug dependence has contributed to the commission of the offence with which they have been charged or convicted. The article focuses on legally coerced treatment for drink-driving offenders and heroin-dependent property offenders. it outlines the various arguments that have been made for providing such treatment under legal coercion, namely. the over-representation of alcohol and drug dependent persons in prison populations; the contributory causal role of alcohol and other drug problems in the offences that lead to their imprisonment; the high rates of relapse to drug use and criminal involvement after incarceration; the desirability of keeping injecting heroin users out of prisons as a way of reducing the transmission of infectious diseases such as HIV and hepatitis; and the putatively greater cost-effectiveness of treatment compared with incarceration. The ethical objections to legally coerced drug treatment are briefly discussed before the evidence on the effectiveness of legally coerced treatment for alcohol and other drug dependence is reviewed. The evidence, which is primarily from the USA, gives qualified support for some forms of legally coerced drug treatment provided that these programs are well resourced, carefully implemented, and their performance is monitored to ensure that they provide a humane and effective alternative to imprisonment. Expectations about what these programs can achieve also need to be realistic.

Crack Cocaine Use in Barcelona: A Reason of Worry

In Spain, crack cocaine use is silently increasing. In Barcelona, an intentional sample was selected to describe the general characteristics of this consumption. Participants were submitted to an interview and data were analyzed through qualitative research procedures. Users are young males and of low socioeconomic status and formal education. The major pattern of use is compulsive. Illegal income activities are the choice for crack cocaine or money acquisition, increasing individual and social health costs. Polydrug use is a matter of concern. Although these findings can not be generalized, they should be considered for the development of public policies to adequately address crack cocaine users` needs.

Illicit Opiate Abuse

Illicit opiate use, especially injected drugs, contributes to premature mortality and morbidity in many developed and developing societies. The economic costs of illicit drug use are substantial. Fatal overdoses and HIV/AIDS resulting from sharing dirty needles and injecting equipment are major contributors to mortality and morbidity. Illicit opioid use accounted for 0.7 percent of global disability–adjusted life years in 2000. An estimated 15.3 million people, or 0.4 percent of the world population ages 15 to 64, used illicit opioids in 2002, with more than half using heroin and the rest using opium or diverted pharmaceuticals such as buprenorphine, methadone, or morphine. The most popular interventions for illicit opioid dependence in many developed societies have been law enforcement efforts to interdict the drug supply and enforce legal sanctions against drug use. One consequence has been that illicit opioid users have been exposed to the least effective intervention: imprisonment for drug or property offenses. The most effective intervention to reduce blood–borne virus infection resulting from illicit drug injections is provision of clean injecting equipment to users. This intervention has been widely supported in developed countries, but less so in developing countries. In addition, vaccinations are effective against hepatitis B. In treatment settings, the most popular interventions have been detoxification and drug–free treatment, which has proven the least productive in retaining opioid–dependent people in treatment. Opioid agonists have a niche role in treatment of opioid dependence, especially if their efficacy improves with development of long–acting injectable forms of the drug.

Breaking the deadlock over an Australian trial of injectable opioid maintenance

INJECTABLE HEROIN MAINTENANCE has been advocated as a form of treatment for opioid dependence that would attract, and retain in treatment, addicts who have either not sought treatment or who have failed at other forms of treatment, including methadone maintenance. Advocates of heroin maintenance argue that it would increase the proportion of addicts in treatment and reduce heroin use, drug related crime, and deaths due to overdose.

Heroin overdose: Research and evidence-based intervention

Drug overdose is a major cause of Premature death and morbidity among heroin users. This article examines recent research into heroin overdose to inform interventions that will reduce the rate of overdose death. The demographic characteristics of overdose cases are discussed, including factors associated with overdose: polydrug use, drug purity, drug tolerance, routes of administration, and suicide. Responses by heroin users at overdoses are also examined. Potential interventions to reduce the rate of overdose and overdose-related morbidity are examined in light of the emerging data in this field.

First use of multiple substances: Identification of meaningful patterns

Context: Understanding the process through which adolescents and young adults are trying legal and illegal substances is a crucial point for the development of tailored prevention and treatment programs. However, patterns of substance first use can be very complex when multiple substances are considered, requiring reduction into a few meaningful number of categories. Data: We used data from a survey on adolescent and young adult health conducted in 2002 in Switzerland. Answers from 2212 subjects aged 19 and 20 were included. The first consumption ever of 10 substances (tobacco, cannabis, medicine to get high, sniff (volatile substances, and inhalants), ecstasy, GHB, LSD, cocaine, methadone, and heroin) was considered for a grand total of 516 different patterns. Methods: In a first step, automatic clustering was used to decrease the number of patterns to 50. Then, two groups of substance use experts, three social field workers, and three toxicologists and health professionals, were asked to reduce them into a maximum of 10 meaningful categories. Results: Classifications obtained through our methodology are of practical interest by revealing associations invisible to purely automatic algorithms. The article includes a detailed analysis of both final classifications, and a discussion on the advantages and limitations of our approach.

The P450 oxidoreductase genotype is associated with CYP3A activity in vivo as measured by the midazolam phenotyping test.

CYP3A4, CYP3A5 and CYP3A7 are hepatic enzymes that metabolize about 50% of drugs on the market, with a large overlap in their specificities. We investigated the genetic bases that contribute to the variation of CYP3A activity. We phenotyped 251 individuals from two independent studies (182 patients treated with methadone and 69 patients with clozapine) for CYP3A activity using the midazolam phenotyping test and genotyped them for CYP3A4, CYP3A5, and CYP3A7 genetic variants, including the single nucleotide polymorphism (SNP) rs4646437C>T in intron 7 of CYP3A4. Owing to the fact that CYP enzymes require electron transfer through the P450 oxidoreductase (POR), and functional impairment has been shown for the POR*28 SNP, this polymorphism was also analysed. We show that CYP3A4, CYP3A5 and CYP3A7 genotypes, including the SNP rs4646437C>T, do not reflect the inter-individual variability of CYP3A activity (P>0.1). In contrast, POR*28 TT genotype presents a 1.6-fold increase in CYP3A activity compared with POR*28C carriers (n = 182, P = 0.004). This finding was replicated in the second independent dataset (n = 69, P = 0.04). The SNP POR*28 seems to be a better genetic marker of the variability of total CYP3A activity in vivo than CYP3A4, CYP3A5 and CYP3A7 genetic variants.

Determination of human plasma levels of levo-alpha-acetylmethadol and its metabolites by gas chromatography-mass spectrometry.

A gas chromatography-mass spectrometry (GC-MS) method is presented which allows the simultaneous determination of the plasma concentrations of the levo-alpha-acetylmethadol (LAAM) and of its active metabolites (NorLAAM and DiNorLAAM), after derivatization with the reagent trifluoroacetic anhydride (TFAA). No interferences from endogenous compounds were observed following the extraction of plasma samples from 11 different human subjects. The standard curves were linear over a working range of 5-200ng/ml for the three compounds. Recoveries measured at three concentrations ranged from 47 to 67% for LAAM, from 50 to 69% for NorLAAM and from 28 to 50% for DiNorLAAM. Intra- and interday coefficients of variation determined at three concentrations ranged from 5 to 13% for LAAM, from 3 to 9% for NorLAAM and from 5 to 13% for DiNorLAAM. The limits of quantitation of the method were found to be 4ng/ml for the three compounds. No interference was noted from methadone. This sensitive and specific analytical method could be useful for assessing the in vivo relationship between LAAM's blood levels, clinical efficacy and/or cardiotoxicity

Ruptured pseudo-aneurysm of a femoral artery in a drug abuser revealed by post-mortem CT angiography.

A 35-year-old drug addict was found dead in a public toilet with a ruptured groin, which was later diagnosed to be a leaking pseudo-aneurysm. Investigation at the scene revealed impressive external hemorrhage related to a groin wound. Post-mortem computed tomography angiography demonstrated an aneurysm of the right femoral artery with leak of contrast liquid. Signs of blood loss were evident at autopsy, and histological examination revealed necrosis and rupture of the pseudo-aneurysm. Toxicological analyses were positive for methadone, cocaine, citalopram, and benzodiazepines. This is the first case report in the literature of a ruptured femoral pseudo-aneurysm with a post-mortem radiological diagnosis.

Dépendances: nouveautés en médecine 2008 [Addiction]

L'actualité 2008 des dépendances est centrée sur l'avancée des neurosciences psychiatriques dans le domaine des addictions mais aussi sur les clarifications nécessaires face à la complexité des comorbidités psychiatriques des addictions, notamment en cas de schizophrénie. Enfin, le praticien trouvera des considérations utiles pour la prescription de traitements de substitution chez des patients VIH en trithérapie. The highlights 2008 in the addiction field are correlated to the progress of psychiatric neurosciences. Clarifications are also necessary towards the psychiatric comorbidities (schizophrenia) with the addictions. Then, useful considerations are given for the prescription of substitution treatment among HIV patients under tritherapy.

The rapid urinary drug toxicology screen in the emergency room: a useful tool ?

Intoxications are a frequent problem in the ER. In the vast majorityof cases, supportive treatment is sufficient. Severe intoxications withunknown agents are considered an indication for a urinary drug screen,and are recommended by several toxicology centers. However, theirusefulness for patient management remains uncertain.Study objectives: Evaluation of the impact of a urinary drug screen(Biosite Triage TOX Drug Screen) testing 11 substances(acetaminophen, amphetamines, methamphetamines, barbiturates,benzodiazepines, cocaïne, methadone, opioids, phencyclidine,cannabis, tricyclic antidepressants) on initial adult patient managementin the emergency department of a university hospital with ~35.000annual admissions.Methods: Observational retrospective analysis of all tests performedbetween 09/2009 and 09/2010. A test utility was defined as useful if itresulted in the administration of a specific antidote (Flumazenil/Naloxone), the use of a quantitative confirmatory toxicologic test, or achange in patient's disposition.Results: 57 tests were performed. Patient age was 32 ± 11 (SD) years;58% were men; 30% were also intoxicated with alcohol. Two patientsdied (3.5%): the first one of a diphenhydramin overdose, the other of ahypertensive intracerebral hemorrhage believed to be caused cocaineabuse but a negative urine test. Test indications were: 54% firstpsychotic episode; 25% acute respiratory failure; 18% coma; 12%seizure; 11% opioids toxidrome; 7% sympathicomimetic toxidrome; 5%hypotension; 4% ventricular arrhythmia (VT, VF, torsades de pointes)or long QT. 75% of tests were positives for >=1 substance (mean 1.7 ±0.9). 47% of results were unexpected by history. 18% of resultsinfluenced patient management: 7% had a negative test that confirmedthe diagnosis of endogenous psychosis in a first psychotic episode, andallowed transfer to psychiatry; 5% received flumazenil/naloxone;2% had an acetaminophen blood level after a positive screen; finally,4% had an unexpected methadone abuse that required prolongationof hospital stay.Conclusions: A rapid urinary toxicologic screen was seldom used inour emergency department, and its impact on patient managementwas marginal: only one in 6 tests influenced treatment decisions.