Towards adherence monitoring using breath or oral fluid as a matrix in a methadone maintenance treatment program for patients with a chronic heroin use disorder: Issues and interpretation of the results.

Urine has been the preferred matrix for monitoring heroin and methadone adherence due to its large detection window. Drawbacks such as privacy concerns and adulteration however require other matrices. The study aims to determine if oral fluid and exhaled breath are suitable alternatives for heroin and methadone monitoring and to assess the detection time in exhaled breath. Forty-three participants, all on methadone and heroin-assisted treatment, were studied. Participants were monitored after the first and right before the second dosage of heroin. At both time points, oral fluid and exhaled breath samples were collected with urine at the second time point. All samples were screened for opiates, methadone and other drugs using immunoassay and LC-MS-MS. At the second time point, 98% of oral fluid samples and all exhaled breath samples tested positive for 6-monoacetylmorphine (6-MAM). Regarding morphine detection, the findings were reversed (100% in oral fluid, 98% in exhaled breath). Methadone-related results were 100% positive across all matrices, as expected. Notable is the detection of the heroin marker acetylcodeine in oral fluid and exhaled breath samples, which resulted in relatively low negative predictive value (average 54.6%). Oral fluid and exhaled breath are suitable alternatives for heroin and methadone maintenance monitoring. Clinicians should consider ease of collection, adulteration risk, costs, turn-around time and the substance of interest while choosing a matrix. In addition, even in cases when medicinal heroin is used, medical professionals should be aware of the presence of acetylcodeine in these alternate matrices.

Can Breaking Heroin Addiction Lead to a Broken Heart? A Case of Reverse Takotsubo Cardiomyopathy in a Patient With Heroin Withdrawal.

Reverse takotsubo cardiomyopathy is triggered by emotional or physical stress and has a presentation similar to that of acute coronary syndrome. A 39-year-old woman with a history of heroin use disorder presented with intractable nausea, vomiting, and diarrhea. She was diagnosed with heroin withdrawal and started on buprenorphine-naloxone. On day 2 of her hospitalization, she developed chest heaviness and had an elevated troponin I level of 3.2 ng/mL (reference range, 0.015-0.045 ng/mL); electrocardiography showed new T-wave inversions in the anterior and inferior leads. Emergent coronary angiography showed patent coronary arteries, and left ventriculography showed basal hypokinesis and apical hyperkinesis, consistent with reverse takotsubo cardiomyopathy secondary to heroin withdrawal. She was started on antihypertensive agents, and her buprenorphine-naloxone dose was increased. At her 3-month follow-up visit, she reported no symptoms consistent with angina or heart failure. This appears to be the first report of heroin withdrawal causing reverse takotsubo cardiomyopathy. Awareness of this association can lead to earlier recognition and treatment of reverse takotsubo cardiomyopathy.

6-Monoacetylmorphine-antibody distribution in tissues from heroin-related death cases: An experimental study to investigate the distributive response.

Heroin, a semisynthetic opioid drug synthesized from morphine, is the 3,6-diacetyl ester of morphine (diacetylmorphine). The post-mortem diagnosis of heroin-related death could be an issue and usually rely on a combination of investigations, including the autopsy, histological and toxicological analysis. We conducted the present study to evaluate the correlation between the heroin concentration in biological fluids (peripheral blood, bile and urine) and the post-mortem anti-6-MAM antibody expression in various tissues (brain, heart, lung, liver and kidney) using immunohistochemical staining. A quantitative analysis of the immunohistochemical reaction was carried out. 45 cases of heroin-related death investigated at the Forensic Pathology Institutes of the University of Rome, Foggia and Pisa were included. The control group was composed of 15 cases of death due to other causes, without brain lesions and negative toxicological analysis for drugs. We found a positive immunohistochemical reaction in different organs and it was related to the timing of heroin metabolization. No reaction was found in the control group. Our findings show that immunohistochemistry can be a valuable tool for the post-mortem diagnosis of acute heroin abuse. A better understanding of the timing of heroin's metabolism can be useful in the forensic field and for future therapeutic applications.

Heroin Fatality in a Feline: A Case Report with Postmortem Liver Concentrations.

A case of feline intoxication and fatality with the illicit drug heroin is described. A 5-year-old castrated male domestic shorthair cat was recently diagnosed with an active pneumonitis and left at home for a couple of days under the care of another resident. Upon return, the owner found his cat dead with strong suspicion of foul play. The cat was necropsied by a local veterinary clinic to retrieve the liver for diagnostic toxicology. The postmortem liver sample screened positive for 6-acetylmorphine and 6-acetylcodeine by gas chromatography mass spectrometry. Deconvolution techniques were applied to chromatograms, which revealed the additional presence of morphine and mirtazapine. Subsequent quantitation of mirtazapine, heroin, morphine, 6-acetylmorphine and 6-acetylcodeine was performed by gas chromatography--tandem quadrupole mass spectrometry. Although companion animal fatalities arising from toxicities are a likely consequence of drug abuse in a home, this is the first reported case of a malicious feline fatality resulting from heroin with quantitation of heroin metabolites.

Bidirectional influence of heroin and cocaine escalation in persons with dual opioid and cocaine dependence diagnoses.

Persons with dual severe opioid and cocaine use disorders are at risk of considerable morbidity, and the bidirectional relationship of escalation of mu-opioid agonists and cocaine use is not well understood. The aim of this study was to examine the bidirectional relationship between escalation of heroin and cocaine use in volunteers dually diagnosed with opioid and cocaine dependence (OD + CD). Volunteers from New York with OD + CD (total n = 295; male = 182, female = 113; age ≥ 18 years) were interviewed with the Structured Clinical Interview for the DSM-IV Axis I Disorders and Kreek-McHugh-Schluger-Kellogg scales for dimensional measures of drug exposure, which also collect ages of 1st use and onset of heaviest use. Time of escalation was defined as age of onset of heaviest use minus age of 1st use in whole years. Times of escalation of heroin and cocaine were positively correlated in both men (Spearman r = .34, 95% confidence interval [CI: .17, .48], p < .0001) and women (Spearman r = .51, [.27, .50], p < .0001) volunteers. After we adjusted for demographic variables, a Cox regression showed that time of cocaine escalation was a predictor of time of heroin escalation (hazard ratio [HR] = 0.97, 95% CI [0.95, 0.99], p = .003). Another Cox regression showed that this relationship is bidirectional, because time of heroin escalation was also a predictor of time of cocaine escalation (HR = 0.98, [0.96-0.99], p = .016). In these adjusted models, gender was not a significant predictor of time of escalation of either heroin or cocaine. Therefore, escalation did not differ robustly by gender when adjusting for demographics and other major variables. Overall, rapid escalation of cocaine use was a predictor of rapid escalation of heroin use, and vice versa, in persons with dual severe opioid and cocaine use disorders. These findings suggest a shared vulnerability to rapid escalation of these 2 drugs in persons with dual severe opioid and cocaine use disorders. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Association between GABA receptor delta subunit gene polymorphisms and heroin addiction.

Evidence suggests that γ-aminobutyric acid (GABA) receptors are involved in the development of drug dependence. Considering its exclusively extrasynaptic localization, GABA receptor delta subunit (GABRD) is likely involved in heroin addiction. The purpose of this study was to explore the association between the single nucleotide polymorphisms (SNPs) of GABRD and heroin addiction. Genotyping of five SNPs (rs13303344, rs4481796, rs2376805, rs2229110, and rs41307846) in GABRD gene was performed by using TaqMan SNP assay. The association between heroin addiction and these SNPs was assessed in 446 heroin dependent patients and 400 normal control subjects of male Han Chinese origin. Only the genotype and allele frequencies at rs13303344 differed significantly between the cases and controls (nominal P values were 0.028 and 0.019, respectively). The C allele of rs13303344 was associated with an increased risk of heroin addiction (OR = 1.281, 95 % CI: 1.042-1.575). After Bonferroni correction, the association lost significance. The frequencies of the haplotype C-C-A and A-C-A at GARBD (rs13303344-rs4481796- rs2376805) differed significantly between the cases and controls. The heroin craving score was significantly higher in patients with CC/AC genotypes at rs13303344 than in those with the AA genotype (nominal P = 0.017). The results suggest that GABRD rs13303344 may contribute to the susceptibility to heroin addiction and is associated with the drug cravings of heroin dependent patients.

Can the migration process influence the clinical expression of heroin use disorder in migrants to Italy?

BACKGROUND: For some time now, there has been a strong consensus that the migration process can influence the onset, course, development, outcome, and clinical aspects of psychiatric pathologies. METHODS: In this study, we have analyzed the influence of the migration process on the clinical expression of heroin use disorder (HUD). In a naturalistic case-control study, we compared, both at univariate and multivariate level, 30 migrant HUD (M-HUD) patients with 30 age/gender-matched Italian HUD (IT-HUD) patients. We also analyzed demographic data, drug addiction history, psychopathological symptoms, addictive behavior, and emotional reactivity to life events. RESULTS: Compared with IT-HUD pairs, at HUD Agonist Opioid Treatment, M-HUD patients were characterized by inadequate income and the presence of legal problems. They were more frequently at stage 3 of heroin addiction, with a concomitantly less frequent use of stimulants. Their age at the onset of heroin use was greater than that of subjects in the IT-HUD group. HUD post-traumatic stress disorder spectrum was present and was more severe in all M-HUD patients, but grief reactions and maladaptive behavior were the most discriminant traits. No differences were found in terms of addictive behaviors related to heroin craving or with respect to the severity/typology of psychopathology specific to HUD. CONCLUSIONS: The migratory process does not seem to be correlated with addictive behaviors or with psychopathology specific to HUD. It partly affects HUD history, and specifically correlates with emotional reactivity to loss and traumatic life events, so suggesting that in M-HUD individuals, the link between the migratory syndrome and HUD is very close.

Measurement invariance and psychometric properties of Perceived Stigma toward People who use Substances (PSPS) among three types of substance use disorders: Heroin, amphetamine, and alcohol.

BACKGROUND: The 8-item self-report Perceived Stigma toward Substance Users Scale (PSAS) is a commonly used instrument to assess stigma for people with substance use disorders. This study aimed to develop and validate the Taiwan version of the PSAS entitled Perceived Stigma toward People who use Substances - Taiwan version (PSPS-TV) among individuals with substance use disorders. METHODS: Patients with substance use disorders (N = 300; mean age = 45.22; 255 males) completed the PSPS-TV, Self-Stigma Scale-Short (SSS-S), Taiwan Depression Questionnaire (TDQ), and Rosenberg Self-Esteem Scale (RSES). Confirmatory factor analysis was used to test the construct validity and the measurement invariance of the PSPS-TV. Concurrent validity was tested using the correlations between PSPS-TV and SSS-S, TDQ, and RSES scores. RESULTS: The confirmatory factor analysis supported the construct validity and measurement invariance of the PSPS-TV. SSS-S scores explained 13 %, TDQ scores explained 10 % and RSES scores explained 17 % of the PSPS-TV score variance with moderate standardized coefficients (0.38, 0.32 and -0.42, respectively; all p < 0.001). CONCLUSIONS: The PSPS-TV is an appropriate instrument to assess perceived stigma for individuals residing in Taiwan who have substance use disorders. Taiwan healthcare providers may thus consider using the PSPS-TV to assess perceived stigma relating to substance use in Taiwan.

Daily heroin injection and psychiatric disorders: A cross-sectional survey among People Who Inject Drugs (PWID) in Haiphong, Vietnam.

BACKGROUND: Psychiatric comorbidities are frequent among people who inject drugs, they are associated with a poorer prognosis and need to be addressed. Their interaction with daily heroin injection requires clarification. METHODS: A cross-sectional survey was conducted among PWID recruited in the city of Haiphong, Vietnam, by respondent-driven sampling. The inclusion criteria were age 18 or older and current injection drug use, verified by skin marks and positive urine tests for heroin or methamphetamine. Data on socio-demographic characteristics, drug use, sexual behaviour and access to treatment were collected using face-to-face questionnaires by trained interviewers. PWID were screened by trained psychiatrists for depression, psychotic disorder and suicidality, using the MINI questionnaire. RESULTS: 418 participants were included in the analyses. All were injected heroin users, 21 % were diagnosed with a current major depressive disorder, 15 % with a current psychotic disorder and 12 % presented a suicide risk. In the bivariate analyses, regular meth use, cannabis use and ketamine use were positively associated with presenting at least one psychiatric condition while daily heroin injection and being currently treated with methadone were negatively associated. In the multivariate model, poly-substance use was positively associated with depression (methamphetamine and drinking in addition to heroin) and psychotic disorder (methamphetamine and/or hazardous drinking in addition to heroin) while daily heroin injection and current methadone treatment were negatively and independently associated with depression and psychotic syndrome. CONCLUSIONS: Our survey confirms the burden of methamphetamine use and the protective effect of methadone but also a possible protective effect of daily heroin injection.

Prevalence of obesity among U.S. population with substance dependence.

AIM: To investigate associations between substance dependence and obesity. METHODS: Obesity (body mass index ≥ 30 kg/m2) status and the status of dependence on heroin, stimulant, marijuana, nicotine and alcohol (past-month status for nicotine and past-year status for all others) were identified from the U.S. National Survey on Drug Use and Health (NSDUH, 2015-2017) datasets. SAS Surveylogistic regression was used to estimate adjusted odds ratio (AOR) for the association between each substance dependence and obesity, adjusting for potentially confounding effects of sociodemographic factors and health condition. RESULTS: It was estimated that 10.6 % of noninstitutional U.S. residents aged 12 years or older were nicotine-dependent, 3.0 % alcohol-dependent, 1.0 % marijuana-dependent, 0.6 % stimulant-dependent, and 0.2 % heroin-dependent. Heroin-dependent individuals had 59 % lower odds of obesity relative to their non-dependent counterparts (AOR = 0.41; 95 % CI: 0.28-0.60; p < 0.0001). Lower odds of obesity were also noted for marijuana-dependent (AOR = 0.64; 95 % CI: 0.56-0.73; p < 0.0001), nicotine-dependent (AOR = 0.68; 95 % CI: 0.64-0.72; p < 0.0001) and alcohol-dependent (AOR = 0.77, 95 % CI: 0.69-0.84; p < 0.0001) individuals, but not statistically significant for stimulant-dependent individuals (AOR = 0.84; 95 % CI: 0.68-1.02; p = 0.0825). CONCLUSIONS: Heroin, marijuana, nicotine and alcohol dependence were associated with lower odds of obesity than their non-dependence counterparts. Main findings based on 2015-2017 NSDUH are consistent with findings from our prior report based on clinical trials data from National Institute on Drug Abuse Clinical Trials Network, and other epidemiological evidence in the literature. These findings can alert substance abuse treatment professionals to monitor weight change, especially among weight-concerned substance abusers.

The Association between Opioid Discontinuation and Heroin Use: A Nested Case-Control Study.

BACKGROUND: Opioid prescribing guidelines recommend reducing or discontinuing opioids for chronic pain if harms of opioid treatment outweigh benefits. As opioid discontinuation becomes more prevalent, it is important to understand whether opioid discontinuation is associated with heroin use. In this study, we sought to assess the association between opioid discontinuation and heroin use documented in the medical record. METHODS: A matched nested case-control study was conducted in an integrated health plan and delivery system in Colorado. Patients receiving opioid therapy in the study period (January 2006-June 2018) were included. Opioid discontinuation was defined as ≥45 days with no opioids dispensed after initiating opioid therapy. The heroin use onset date represented the index date. Case patients were matched to up to 20 randomly selected patients without heroin use (control patients) by age, sex, calendar time, and time between initiating opioid therapy and the index date. Conditional logistic regression models estimated matched odds ratios (mOR) for the association between an opioid discontinuation prior to the index date and heroin use. RESULTS: Among 22,962 patients prescribed opioid therapy, 125 patients (0.54%) used heroin after initiating opioid therapy, of which 74 met criteria for inclusion in the analysis. The odds of opioid discontinuation were approximately two times higher in case patients (n = 74) than control patients (n = 1045; mOR = 2.19; 95% CI 1.27-3.78). CONCLUSIONS: Among patients prescribed chronic opioid therapy, the observed increased risk for heroin use associated with opioid discontinuation should be balanced with potential benefits.

Evaluation of an immunoassay procedure to measure 6-monoacetylmorphine.

Introduction: 6-Monoacetylmorphine (6-MAM) is a specific metabolite of heroin. Thus, the presence of 6-MAM in urine is a definitive indication of heroin intake. The possibility of having an immunoassay procedure to measure 6-MAM would be a diagnosis tool to discriminate, among opiates-positive, those patients who have consumed heroin and those who have not.Methods: EMIT® II Plus 6-Acetylmorphine Assay was used to measure 6-MAM in urine. The positive opiate screening results were confirmed at the Toxicology laboratory of our hospital by GC-MS.Results: This study includes 63 urine samples from subjects admitted to emergency department with suspicion of opiate consumption. Specificity was evaluated in the two groups of samples studied. In the first group all samples which resulted negative by opiate immunoassay (n = 33) were negative for 6-MAM immunoassay test. Thus, the specificity obtained for 6-MAM immunoassay in this group was 100%. Regarding the second specificity study, performed in positive samples by opiate immunoassay which were negative to 6 MAM by GC-MS, the specificity decreased down to 75%. In the study of sensitivity all samples confirmed as positive to 6-MAM by confirmatory method (GC-MS) resulted positive by the screening method, thus sensitivity obtained was 100%.Discussion: In this study no FN for 6-MAM was observed and therefore the new Emit® II Plus 6- Acetylmorphine Assay procedure has a high NPV, thus a negative result with 6-MAM immunoassay practically excludes heroine consume. The positive results to 6-MAM by immunoassay should be confirmed by a more analytically specific method, such as GCMS.

Trajectories of heroin use predict relapse risk among heroin-dependent patients: A 5-year follow-up study.

OBJECTIVES: The relationship between past drug use trajectory and long-term relapse risk after rehabilitation among heroin-dependent patients remain understudied. The primary objectives were to identify longitudinal heroin use patterns of heroin-dependent patients, to determine the associative factors with trajectories and to investigate the impact of trajectory groups on relapse after finishing compulsory rehabilitation programs. MATERIALS AND METHODS: A total of 564 heroin-dependent patients were recruited from 4 compulsory rehabilitation facilities in Shanghai, China between 2007 and 2008. The baseline data was linked to participants' follow-up data on relapse from official records. Group-based trajectory model was used to identify distinctive drug use trajectory groups. The association between the identified group and heroin relapse risk was then analyzed to understand the role of past drug use trajectory on relapse. RESULTS: Five trajectory groups were identified in this cohort: (1) Rapid Decrease (9.9%); (2) Persistent High (32.0%); (3) Slow Decrease (34.1%); (4) Gradual Increase (4.5%); (5) Persistent Low (19.5%). Gender, age, education, and impulsivity were found to be different between the five groups. During the 5 years after discharged from the compulsory program, 291 (59.0%) individuals relapsed. Multivariate logistic regression analysis showed that the persistent high group (OR: 2.77 [1.46-5.24]), slow decrease group (OR: 2.31 [1.32-4.06]) and gradual increase group (OR: 3.50 [1.18-10.39]) was positively associated with the heroin relapse risk when compared to the persistent low group. CONCLUSIONS: Heroin use trajectories vary among heroin-dependent patients in China. The trajectories of heroin use before compulsory rehabilitation are associated with subsequent long-term relapse risk.

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.

Effect of heroin on right ventricular cardiac performance.

OBJECTIVE: The aim of this study was to investigate the effects of heroin addiction, which is an important social and health problem, on right cardiac function. METHODS: A total of 85 individuals were included in the study. The study group comprised 45 patients smoking heroin and the control group was 40 healthy individuals with no drug addiction. Patients injecting heroin were excluded. Echocardiographic evaluation of patients using heroin was performed and compared with those in the control group. RESULTS: The right ventricle and pulmonary artery diameters in the heroin group were found to be higher compared to the control group. The myocardial performance index (MPI) was higher and more abnormal in the heroin group (0.48 ± 0.22 vs 0.39 ± 0.11, p < 0.05) whereas isovolumic acceleration (IVA) of the right ventricle was significantly lower in the heroin group (2.92 ± 0.69 vs 3.4 ± 0.68 m/s2, p < 0.01). No significant difference was observed between the groups with regard to the right ventricular ejection fraction (RVEF) (59.6 ± 2.5 vs 60.6 ± 2.3%, p = 0.08), tricuspid annular plain systolic excursion (TAPSE) (24.1 ± 4.2 vs 24.5 ± 2.4 mm, p = 0.7), tissue Doppler imaging S wave (TDI-S) (13.7 ± 2.1 vs 13.8 ± 2.1 cm/s, p = 0.86) and right ventricular fractional area change (RVFAC) (42.7 ± 8.3 vs 43.9 ± 3.5%, p = 0.4). Multivariate and univariate regression analyses revealed independent correlation between the pulmonary artery diameter and RVIVA, and heroin addiction. CONCLUSIONS: Heroin addiction negatively affected right ventricular function and more attention should be paid to the cardiac function of these patients.

Reduced response inhibition after exposure to drug-related cues in male heroin abstainers.

RATIONALE: Deficits in response inhibition associated with heroin use could last several months after abstinence in heroin users, and their response inhibition can also be interfered with task-irrelevant drug-related cues. However, it is unclear whether exposure to drug-related cues affects subsequent response inhibition in heroin users following abstinence. OBJECTIVES: The present study aimed to investigate how drug-related cues with different durations between stimulus presentations, referred to as stimulus onset asynchronies (SOAs), affect subsequent response inhibition in heroin abstainers (HAs) with different length of abstinence. METHODS: Sixty-seven male HAs performed a modified Go/NoGo task in which a motor response to frequent Go targets and no response to rare NoGo targets were required and a Go or NoGo target was displayed after either a heroin-related or a neutral picture presented for the 200 ms and 600 ms SOAs. RESULTS: The HAs responded significantly faster to Go targets following the neutral pictures for the 600 ms SOA compared to other conditions. They also made more commission errors following heroin-related pictures compared to neutral pictures regardless of the SOAs. The shorter-term HAs made more commission errors compared to the longer-term HAs following the 200 ms SOA, and it was only a trend when the SOA was 600 ms. Additionally, negative correlations between the duration of current abstinence and commission errors were observed following cues with the 200 ms SOA. CONCLUSIONS: Impaired response inhibition in HAs can be improved through protracted drug abstinence. However, that effect can be reduced by exposure to drug-related cues, which may increase the risk of relapse.

Postmortem Fluid Concentrations of Heroin Biomarkers and Their Metabolites.

Only limited data exist concerning the utility of complementary specimens in heroin-related deaths. As such, this report employed a validated LC-MS-MS method to quantify 6-monoacetylmorphine (6-MAM), 6-acetylcodeine (6-AC), and their metabolites morphine and codeine in blood with (BN) and without preservative (B) and the additional unpreserved specimens of vitreous humor, urine, stomach contents, and bile from 20 postmortem cases in which heroin was the primary cause of death. The median concentration of 6-MAM in BN was 0.011 mg/L, B was 0.008 mg/L, urine was 0.186 mg/L, vitreous humor was 0.022 mg/L, stomach contents was 0.147 mg/L, and bile was 0.012 mg/L. Only one case was found to be positive for 6-AC in B (case 6, 0.002 mg/L), and the median concentration of 6-AC was 0.002 mg/L in BN, 0.012 mg/L in urine, 0.003 mg/L in vitreous humor, 0.057 mg/L in stomach contents, and 0.004 mg/L in bile. These findings present new information on the distribution of these analytes in complementary matrices and support their inclusion for accurately determining the role of heroin in opioid-related deaths.

Causes of hospital admission and mortality among 6683 people who use heroin: A cohort study comparing relative and absolute risks.

BACKGROUND: Mortality in high-risk groups such as people who use illicit drugs is often expressed in relative terms such as standardised ratios. These measures are highest for diseases that are rare in the general population, such as hepatitis C, and may understate the importance of common long-term conditions. POPULATION: 6683 people in community-based treatment for heroin dependence between 2006 and 2017 in London, England, linked to national hospital and mortality databases with 55,683 years of follow-up. METHOD: Age- and sex-specific mortality and hospital admission rates in the general population of London were used to calculate the number of expected events. We compared standardised ratios (relative risk) to excess deaths and admissions (absolute risk) across ICD-10 chapters and subcategories. RESULTS: Drug-related diseases had the highest relative risks, with a standardised mortality ratio (SMR) of 48 (95% CI 42-54) and standardised admission ratio (SAR) of 293 (95% CI 282-304). By contrast, other diseases had an SMR of 4.4 (95% CI 4.0-4.9) and an SAR of 3.15 (95% CI 3.11-3.19). However, the majority of the 621 excess deaths (95% CI 569-676) were not drug-related (361; 58%). The largest groups were liver disease (75 excess deaths) and COPD (45). Similarly, 80% (11,790) of the 14,668 excess admissions (95% CI 14,382-14,957) were not drug-related. The largest groups were skin infections (1073 excess admissions), alcohol (1060), COPD (812) and head injury (612). CONCLUSIONS: Although relative risks of drug-related diseases are very high, most excess morbidity and mortality in this cohort was caused by common long-term conditions.

Initiation into heroin use among street-involved youth in a Canadian setting: A longitudinal cohort study.

BACKGROUND: Emerging evidence suggests that non-medical prescription opioid (NMPO) use may be a risk factor for initiating heroin use; however, pathways from PO to heroin use among youth remain underexplored. We sought to examine the association between NMPO use and heroin initiation. METHODS: Between September 2005 and June 2017 data were derived from an open prospective cohort of street-involved youth aged 14-28 who use illegal drugs in Vancouver, Canada. The study included 526 youth who had never used non-injection heroin, and 652 youth who had never used injection heroin at baseline. We used Cox proportional hazards regressions to examine the association between NMPO use - in addition to other substance use patterns - and subsequent initiation into non-injection and injection heroin use. RESULTS: Among those who had never used non-injection heroin at baseline, 133 (25.3%) initiated non-injection heroin use during the study period. Among those who had never injected heroin at baseline, 137 (21.0%) initiated heroin injection during the study period. In multivariable analyses, NMPO use, crack use, and crystal methamphetamine use predicted non-injection heroin initiation (all p < 0.05). In separate multivariable analyses, non-injection heroin and crystal methamphetamine predicted heroin injection initiation (all p < 0.05). CONCLUSIONS: Among street-involved youth in this setting, NMPO use predicted initiation into non-injection heroin use but not initiation into heroin injection. Interestingly, crack cocaine and crystal methamphetamine use were stronger predictors of heroin initiation than NMPO use was, suggesting that stimulant use may carry greater risks for heroin initiation than NMPO use.