The motives and methods of methamphetamine and 'heroin' co-use in West Virginia.

BACKGROUND: Opioid and methamphetamine co-use is increasing across the USA with overdoses involving these drugs also rising. West Virginia (WV) has led the US in opioid overdose death rates since at least 2013 and rising co-use of methamphetamine with opioids has played a greater role in deaths over the last 5 years. METHODS: This study used rapid ethnography to examine methods and motivations behind opioids and methamphetamine co-use from the viewpoint of their consumers. Participants (n = 30) were people who injected heroin/fentanyl also using methamphetamine who participated in semi-structured interviews. RESULTS: We found multiple methods of co-using opioids and methamphetamine, whether alternately or simultaneously and in varying order. Most prioritized opioids, with motives for using methamphetamine forming three thematic categories: 'intrinsic use', encompassing both inherent pleasure of combined use greater than using both drugs separately or for self-medication of particular conditions; 'opioid assisting use' in which methamphetamine helped people manage their existing heroin/fentanyl use; and 'reluctant or indifferent use' for social participation, reflecting methamphetamine's low cost and easy availability. CONCLUSIONS: Methamphetamine serves multiple functions among people using opioids in WV. Beliefs persist that methamphetamine can play a role in preventing and reversing opioid overdose, including some arguments for sequential use being protective of overdose. 'Reluctant' uptake attests to methamphetamine's social use and the influence of supply. The impact on overdose risk of the many varied co-use patterns needs further investigation.

Longitudinal Opioid Surveillance Project Involving Toxicologic Analysis of Postmortem Specimens from 9 Counties in Michigan Suggests the Discovery of New High-Intensity Drug Trafficking Areas.

ABSTRACT: Acetyl fentanyl (AF) is a Schedule I fentanyl analog that has been increasingly seen in heroin and fentanyl polydrug toxicity overdoses in Michigan (MI). Drug users are often unaware of the presence of AF in their drugs because it is often sold mixed into or disguised as heroin. High levels of AF in heroin drug products can cause increased incidence of overdose. This article describes data from a longitudinal opioid surveillance program and details 102 decedents in MI who were found to have evidence of heroin in their postmortem blood. A large portion of these decedents were also found to have evidence of fentanyl and AF. Our data further show significant overlap in incidence rates of AF and heroin-related overdose deaths in several MI counties, suggesting that AF is becoming enmeshed in heroin trafficking. Furthermore, we report unprecedented high incidence rates of AF and heroin-related overdose deaths in Calhoun county, and we propose that it is a high-intensity drug trafficking area. Highways US-131 and US-31 are likely used to transport these drugs. More study is needed into the drug trafficking trends in MI to ascertain drug sources and monitor the ever developing and dangerous polydrug heroin combinations.

Vascular Injuries in Intravenous Drug Addicts-A Single-Center Experience.

BACKGROUND: Infected false aneurysms (IFA) caused by intravenous drug abuse are uncommon but challenging lesions. The best approach for the surgical management of this condition is still unknown. The aim is to present a single-center 14-year experience in the IFA treatment in intravenous drug abusers, thus providing additional data regarding the treatment options and outcome in these patients. METHODS: A retrospective analysis of 32 consecutive patients with vascular injuries secondary to intravenous drug abuse, during the period from January 2004 to April 2018, was performed. Data of interest were extracted from patients' medical history records, anesthesia charts, and database implemented in daily practice, or were obtained by personal contact. The diagnosis was set based on history, physical examination and/or color Doppler sonography, multidetector computed tomographic angiography, and digital subtraction angiography. The outcome included graft patency, limb amputation, and mortality. RESULTS: During study period, 32 heroin abusers, predominantly males (81%), were surgically treated due to vascular injuries, with mean age of 35.2 years. The vast majority of patients have had an injury of the lower extremity blood vessels (84.3%) and the common femoral artery was the most common site of injury (59.4%). Three-quarters of patients underwent resection of the false aneurysm and ligation of the artery without reconstruction of the blood vessel. In 7 cases (21.9%), arterial reconstruction was performed with overall failure rate of 42.86%. The overall mortality rate was 6.25% and the rate of extremity salvage was 96.7%. CONCLUSIONS: The best treatment option is yet to be found, but based on the results of the present study, ligation of affected artery without revascularization seems to be an efficient, safe, and optimal treatment method, with minor risk of the extremity loss.

Access to Office-Based Buprenorphine Treatment in Areas With High Rates of Opioid-Related Mortality: An Audit Study.

Background: Improving access to treatment for opioid use disorder is a national priority, but little is known about the barriers encountered by patients seeking buprenorphine-naloxone ("buprenorphine") treatment. Objective: To assess real-world access to buprenorphine treatment for uninsured or Medicaid-covered patients reporting current heroin use. Design: Audit survey ("secret shopper" study). Setting: 6 U.S. jurisdictions with a high burden of opioid-related mortality (Massachusetts, Maryland, New Hampshire, West Virginia, Ohio, and the District of Columbia). Participants: From July to November 2018, callers contacted 546 publicly listed buprenorphine prescribers twice, posing as uninsured or Medicaid-covered patients seeking buprenorphine treatment. Measurements: Rates of new appointments offered, whether buprenorphine prescription was possible at the first visit, and wait times. Results: Among 1092 contacts with 546 clinicians, schedulers were reached for 849 calls (78% response rate). Clinicians offered new appointments to 54% of Medicaid contacts and 62% of uninsured-self-pay contacts, whereas 27% of Medicaid and 41% of uninsured-self-pay contacts were offered an appointment with the possibility of buprenorphine prescription at the first visit. The median wait time to the first appointment was 6 days (interquartile range [IQR], 2 to 10 days) for Medicaid contacts and 5 days (IQR, 1 to 9 days) for uninsured-self-pay contacts. These wait times were similar regardless of clinician type or payer status. The median wait time from first contact to possible buprenorphine induction was 8 days (IQR, 4 to 15 days) for Medicaid and 7 days (IQR, 3 to 14 days) for uninsured-self-pay contacts. Limitation: The survey sample included only publicly listed buprenorphine prescribers. Conclusion: Many buprenorphine prescribers did not offer new appointments or rapid buprenorphine access to callers reporting active heroin use, particularly those with Medicaid coverage. Nevertheless, wait times were not long, implying that opportunities may exist to increase access by using the existing prescriber workforce. Primary Funding Source: National Institute on Drug Abuse.

Drug overdose deaths at work, 2011-2016.

Drug overdose fatalities have risen sharply and the impact on US workplaces has not been described. This paper describes US workplace overdose deaths between 2011 and 2016. Drug overdose deaths were identified from the Census of Fatal Occupational Injuries and fatality rates calculated using denominators from the Current Population Survey. Fatality rates were compared among demographic groups and industries. Negative binomial regression was used to analyse trends. Between 2011 and 2016, 760 workplace drug overdoses occurred for a fatality rate of 0.9 per 1 000 000 full-time equivalents (FTEs). Workplace overdose fatality rates significantly increased 24% annually. Workplace overdose fatality rates were highest in transportation and mining industries (3.0 and 2.6 per 1 000 000 FTEs, respectively). One-third of workplace overdose fatalities occurred in workplaces with fewer than 10 employees. Heroin was the single most frequent drug documented in workplace overdose deaths (17%). Workplace overdose deaths were low, but increased considerably over the six-year period. Workplaces are impacted by the national opioid overdose epidemic.

Mortality rate in patients on methadone treatment and infected with the human immunodeficiency virus and/or the hepatitis C virus. / Mortalidad entre los pacientes en tratamiento con metadona e infectados con el virus de la inmunodeficiencia humana y/o hepatitis C.

Letter to the editor.

Carta al editor.

Trends in Black and White Opioid Mortality in the United States, 1979-2015.

BACKGROUND: Recent research on the US opioid epidemic has focused on the white or total population and has largely been limited to data after 1999. However, understanding racial differences in long-term trends by opioid type may contribute to improving interventions. METHODS: Using multiple cause of death data, we calculated age-standardized opioid mortality rates, by race and opioid type, for the US resident population from 1979 to 2015. We analyzed trends in mortality rates using joinpoint regression. RESULTS: From 1979 to 2015, the long-term trends in opioid-related mortality for Earlier data did not include ethnicity so this is incorrect. It is all black and all white residents in the US. blacks and whites went through three successive waves. In the first wave, from 1979 to the mid-1990s, the epidemic affected both populations and was driven by heroin. In the second wave, from the mid-1990s to 2010, the increase in opioid mortality was driven by natural/semi-synthetic opioids (e.g., codeine, morphine, hydrocodone, or oxycodone) among whites, while there was no increase in mortality for blacks. In the current wave, increases in opioid mortality for both populations have been driven by heroin and synthetic opioids (e.g., fentanyl and its analogues). Heroin rates are currently increasing at 31% (95% confidence interval [CI] = 27, 35) per year for whites and 34% (95% CI = 30, 40) for blacks. Concurrently, respective synthetic opioids are increasing at 79% (95% CI = 50, 112) and 107% (95% CI = -15, 404) annually. CONCLUSION: Since 1979, the nature of the opioid epidemic has shifted from heroin to prescription opioids for the white population to increasing of heroin/synthetic deaths for both black and white populations. See video abstract at, http://links.lww.com/EDE/B377.

Standard Death Certificates Versus Enhanced Surveillance to Identify Heroin Overdose-Related Deaths.

OBJECTIVES: To compare 2 approaches to identifying heroin-related deaths in cases of overdose: standard death certificates and enhanced surveillance. METHODS: We reviewed Maryland death certificates from 2012 to 2015 in cases of overdose to determine specific mentions of heroin. Counts were compared with estimates obtained through an enhanced surveillance approach that included a protocol considering cause of death, toxicology, and scene investigation findings. RESULTS: Death certificates identified 1130 heroin-related deaths. Enhanced surveillance identified 2182 cases, nearly double the number found through the standard approach. The major factors supporting enhanced surveillance in identifying cases were the presence of morphine, either alone or in combination with quinine, and scene investigation information suggesting heroin use. CONCLUSIONS: Death certificates, the primary source of state and national data on overdose deaths, may underestimate the contribution of heroin to drug-related mortality. Enhanced surveillance efforts should be considered to allow a better understanding of the contribution of heroin to the overdose crisis. Public Health Implications. If enhanced surveillance can be incorporated into the death certificate process, national data on overdoses may better reflect the contribution of heroin to the opioid crisis.

Modeling Health Benefits and Harms of Public Policy Responses to the US Opioid Epidemic.

OBJECTIVES: To estimate health outcomes of policies to mitigate the opioid epidemic. METHODS: We used dynamic compartmental modeling of US adults, in various pain, opioid use, and opioid addiction health states, to project addiction-related deaths, life years, and quality-adjusted life years from 2016 to 2025 for 11 policy responses to the opioid epidemic. RESULTS: Over 5 years, increasing naloxone availability, promoting needle exchange, expanding medication-assisted addiction treatment, and increasing psychosocial treatment increased life years and quality-adjusted life years and reduced deaths. Other policies reduced opioid prescription supply and related deaths but led some addicted prescription users to switch to heroin use, which increased heroin-related deaths. Over a longer horizon, some such policies may avert enough new addiction to outweigh the harms. No single policy is likely to substantially reduce deaths over 5 to 10 years. CONCLUSIONS: Policies focused on services for addicted people improve population health without harming any groups. Policies that reduce the prescription opioid supply may increase heroin use and reduce quality of life in the short term, but in the long term could generate positive health benefits. A portfolio of interventions will be needed for eventual mitigation.

Cost-Effectiveness of Take-Home Naloxone for the Prevention of Overdose Fatalities among Heroin Users in the United Kingdom.

BACKGROUND: Heroin overdose is a major cause of premature death. Naloxone is an opioid antagonist that is effective for the reversal of heroin overdose in emergency situations and can be used by nonmedical responders. OBJECTIVE: Our aim was to assess the cost-effectiveness of distributing naloxone to adults at risk of heroin overdose for use by nonmedical responders compared with no naloxone distribution in a European healthcare setting (United Kingdom). METHODS: A Markov model with an integrated decision tree was developed based on an existing model, using UK data where available. We evaluated an intramuscular naloxone distribution reaching 30% of heroin users. Costs and effects were evaluated over a lifetime and discounted at 3.5%. The results were assessed using deterministic and probabilistic sensitivity analyses. RESULTS: The model estimated that distribution of intramuscular naloxone, would decrease overdose deaths by around 6.6%. In a population of 200,000 heroin users this equates to the prevention of 2,500 premature deaths at an incremental cost per quality-adjusted life year (QALY) gained of £899. The sensitivity analyses confirmed the robustness of the results. CONCLUSIONS: Our evaluation suggests that the distribution of take-home naloxone decreased overdose deaths by around 6.6% and was cost-effective with an incremental cost per QALY gained well below a £20,000 willingness-to-pay threshold set by UK decision-makers. The model code has been made available to aid future research. Further study is warranted on the impact of different formulations of naloxone on cost-effectiveness and the impact take-home naloxone has on the wider society.

A comparison of liver disease mortality with HIV and overdose mortality among Georgia prisoners and releasees: a 2-decade cohort study of prisoners incarcerated in 1991.

OBJECTIVES: We investigated whether eventual causes of death among a cohort of inmates imprisoned in the southeastern United States differed from those in previous prisoner studies. METHODS: We matched 23 510 prisoners in Georgia, a state with historically low levels of heroin consumption but moderate amounts of injection drug use, who were incarcerated on June 30, 1991, to death registries through 2010. Main exposure was 4-year time intervals over 2 decades of observation; main outcome was mortality from liver disease, HIV, and overdose. RESULTS: Although the HIV-related mortality rate exceeded that from liver-related conditions before 2003, liver disease subsequently surpassed HIV as a cause of death. Among 3863 deaths, 22 (0.6%) occurred within 2 weeks after release from prison. Of these, only 2 were caused by accidental poisoning (likely drug overdose). Cardiovascular disease and cancer were the most frequent causes of death in this aging cohort. CONCLUSIONS: Our study design deemphasized immediate deaths but highlighted long-term sequelae of exposure to viral hepatitis and alcohol. Treating hepatitis C and implementing interventions to manage alcohol use disorders may improve survival among prisoners in the Southeast.

Correspondence: Some general points regarding Ledberg and Wennberg, BMC Medical Research Methodology 2014 April 27;14:58.

The purpose of this note is to contribute some general points on a recent paper by Ledberg and Wennberg (BMC Med Res Meth 14:58, 2014) which need to be rectified. They advocate the capture-removal estimator. First, we will discuss drawbacks of this estimator in comparison to the Lincoln-Petersen estimator. Second, we show that their evaluation of the Chao estimator is flawed. We conclude that some statements in Ledberg and Wennberg with respect to Chao's estimator and removal estimation need to be taken with great caution.

Lethality of Opioid Overdose in a Community Cohort of Young Heroin Users.

BACKGROUND: The aim of the study was to estimate the lethality of opioid overdose among young heroin users. METHODS: A prospective community cohort study was conducted in Barcelona and Madrid, Spain. Participants included 791 heroin users aged 18-30 years who were followed up between 2001 and 2006. Fatal overdoses were identified by record linkage of the cohort with the general mortality register, while non-fatal overdoses were self-reported at baseline and follow-up interviews. The person-years (py) at risk were computed for each participant. Fatal and non-fatal overdose rates were estimated by city. Transition towards injection shortly before the overdose could not be measured. Overdose lethality (rate of fatal overdose in proportion to total overdose) and its 95% CI was estimated using Bayesian models. RESULTS: The adjusted rates of fatal and non-fatal opioid overdose were 0.7/100 py (95% CI: 0.4-1.1) and 15.8/100 py (95% CI: 14.3-17.6), respectively. The adjusted lethality was 4.2% (95% CI: 2.5-6.5). CONCLUSIONS: Four out of 100 opioid overdoses are fatal. These are preventable deaths that could be avoided before or after the overdose takes place. Resources are urgently needed to prevent fatal opioid overdose.

Mortality in the Melbourne injecting drug user cohort study (MIX).

BACKGROUND: There are few studies of mortality amongst people who inject drugs (PWID) in Australia. In this study, we estimate mortality in a cohort of PWID in Melbourne and examine predictors of mortality including health service use, demographic characteristics, drug use and personal wellbeing. FINDINGS: We linked identifiers from the Melbourne injecting drug use cohort study (MIX; n = 655) to the National Death Index from 2008 to 2012 to estimate standardised mortality ratios (SMRs). Cox regression was used to examine the bivariate relationship between exposures determined at baseline and subsequent mortality. There were 24 (3.6%) deaths over the study period. The mortality rate in the cohort was 1.0 per 100 PY (95% CI 0.71-1.57), with an SMR of 17.3 (95 % CI 11.6-25.8). Baseline reports of four or more lifetime incarcerations (HR 3.65, 95 % CI 1.16-11.52), past month ambulance attendance (HR 4.43, 95 % CI 1.76-11.17), past month emergency department presentation (HR 3.44, 95 % CI 1.47-8.03) and past 6-month self-reported heroin overdose (HR 3.14, 95 % CI 1.24-7.96) were associated with increased mortality risk. CONCLUSIONS: Contact with emergency services, particularly for drug overdose, remains a lost opportunity to provide referrals for harm reduction and naloxone training programmes to PWID at greater risk of mortality.

Mortality Risk Among Heroin Abusers: Clients and Non-clients of Public Treatment Centers for Drug Addiction.

UNLABELLED: In Europe, the prevalence of problematic heroin consumption is declining but, in spite of the constant rise in the number of treated patients, many of them do not turn to a public treatment center (PTC) for their drug addiction. The aim of this study is to study the mortality risk separately for heroin abusers PTC clients and non-PTC clients (i.e., those never treated at a PTC). METHODS: Cohort study on 959 subjects resident in the metropolitan area of Bologna who went to a health service (i.e., hospital, emergency unit) or to a PTC following problems due to heroin abuse for the first time between 01/01/2004 and 31/12/2009. Standardized mortality ratios (SMRs) were calculated, and regression analysis using the Poisson method was used. RESULTS: Elevated and statistically significant SMRs were found in both genders, irrespective of the contact facility, being higher for PTC clients. Among non-PTC clients 28% of deaths overall were from AIDS or infectious diseases (6% PTC clients), 17% from opiate overdose (6% PTC clients) and 14% from violent causes (6% PTC clients). Multivariate analysis showed a higher mortality risk for patients who used both heroin and cocaine and for concomitant abuse of benzodiazepines. CONCLUSIONS: The characteristics of patients never before treated for addiction prompts a reflection on the presence of a hidden group of patients who are hard to reach, who have a high mortality risk and who turn to health care treatment facilities only in the event of an emergency.

Adolescents at risk: pain pills to heroin: part II.

Casually exposing adolescents to prescription opioid agents may escalate to daily use. A trend exists for adolescents using prescription opioid agents to substitute heroin because it is significantly cheaper than pills (approximately half of the cost) and is often more readily available. Additionally, it is more potent than most prescription opioid agents and carries increased risks of overdose and death. Although treatment for substance use disorders has traditionally centered on total abstinence, opioid replacement therapy (ORT) is an option that saves lives and prevents overdose deaths. In the United States, ORT is based on two medicines: methadone and buprenorphine. These drugs can be substituted for other opiate agents and have much lower overdose risks. Nursing implications and web-based resources for teaching are presented.

Genetic-epigenetic interaction modulates µ-opioid receptor regulation.

Genetic and epigenetic mechanisms play important roles in protein expression, although at different levels. Genetic variations can alter CpG sites and thus influence the epigenetic regulation of mRNA expression, providing an increasingly recognized mechanism of functional consequences of genetic polymorphisms. One of those genetic effects is the association of reduced µ-opioid receptor expression with the functional genetic variant N40D (OPRM1 118A>G, rs1799971) that causes an amino acid exchange in the extracellular terminal of the µ-opioid receptor. We report that the nucleotide exchange at gene position +118 introduces a new CpG-methylation site into the OPRM1 DNA at position +117. This leads to an enhanced methylation of the OPRM1 DNA at this site and downstream. This epigenetic mechanism impedes µ-opioid receptor upregulation in brain tissue of Caucasian chronic opiate addicts, assessed postmortem. While in wild-type subjects, a reduced signalling efficiency associated with chronic heroin exposure was compensated by an increased receptor density, this upregulation was absent in carriers of the 118G receptor variant due to a diminished OPRM1 mRNA transcription. Thus, the OPRM1 118A>G SNP variant not only reduces µ-opioid receptor signalling efficiency, but, by a genetic-epigenetic interaction, reduces opioid receptor expression and therefore, depletes the opioid system of a compensatory reaction to chronic exposure. This demonstrates that a change in the genotype can cause a change in the epigenotype with major functional consequences.

Estimating the size of hidden populations from register data.

BACKGROUND: Prevalence estimates of drug use, or of its consequences, are considered important in many contexts and may have substantial influence over public policy. However, it is rarely possible to simply count the relevant individuals, in particular when the defining characteristics might be illegal, as in the drug use case. Consequently methods are needed to estimate the size of such partly 'hidden' populations, and many such methods have been developed and used within epidemiology including studies of alcohol and drug use. Here we introduce a method appropriate for estimating the size of human populations given a single source of data, for example entries in a health-care registry. METHODS: The setup is the following: during a fixed time-period, e.g. a year, individuals belonging to the target population have a non-zero probability of being "registered". Each individual might be registered multiple times and the time-points of the registrations are recorded. Assuming that the population is closed and that the probability of being registered at least once is constant, we derive a family of maximum likelihood (ML) estimators of total population size. We study the ML estimator using Monte Carlo simulations and delimit the range of cases where it is useful. In particular we investigate the effect of making the population heterogeneous with respect to probability of being registered. RESULTS: The new estimator is asymptotically unbiased and we show that high precision estimates can be obtained for samples covering as little as 25% of the total population size. However, if the total population size is small (say in the order of 500) a larger fraction needs to be sampled to achieve reliable estimates. Further we show that the estimator give reliable estimates even when individuals differ in the probability of being registered. We also compare the ML estimator to an estimator known as Chao's estimator and show that the latter can have a substantial bias when applied to epidemiological data. CONCLUSIONS: The population size estimator suggested herein complements existing methods and is less sensitive to certain types of dependencies typical in epidemiological data.