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Opioid agonist treatment scale-up and the initiation of injection drug use: A dynamic modeling analysis.

ABSTRACT: BACKGROUND:Injection drug use (IDU) is associated with multiple health harms. The vast majority of IDU initiation events (in which injection-naïve persons first adopt IDU) are assisted by a person who injects drugs (PWID), and as such, IDU could be considered as a dynamic behavioral transmission process. Data suggest that opioid agonist treatment (OAT) enrollment is associated with a reduced likelihood of assisting with IDU initiation. We assessed the association between recent OAT enrollment and assisting IDU initiation across several North American settings and used dynamic modeling to project the potential population-level impact of OAT scale-up within the PWID population on IDU initiation. METHODS AND FINDINGS:We employed data from a prospective multicohort study of PWID in 3 settings (Vancouver, Canada [n = 1,737]; San Diego, United States [n = 346]; and Tijuana, Mexico [n = 532]) from 2014 to 2017. Site-specific modified Poisson regression models were constructed to assess the association between recent (past 6 month) OAT enrollment and history of ever having assisted an IDU initiation with recently assisting IDU initiation. Findings were then pooled using linear mixed-effects techniques. A dynamic transmission model of IDU among the general population was developed, stratified by known factors associated with assisting IDU initiation and relevant drug use behaviors. The model was parameterized to a generic North American setting (approximately 1% PWID) and used to estimate the impact of increasing OAT coverage among PWID from baseline (approximately 21%) to 40%, 50%, and 60% on annual IDU initiation incidence and corresponding PWID population size across a decade. From Vancouver, San Diego, and Tijuana, respectively, 4.5%, 5.2%, and 4.3% of participants reported recently assisting an IDU initiation, and 49.4%, 19.7%, and 2.1% reported recent enrollment in OAT. Recent OAT enrollment was significantly associated with a 45% lower likelihood of providing recent IDU initiation assistance among PWID (relative risk [RR] 0.55 [95% CI 0.36-0.84], p = 0.006) compared to those not recently on OAT. Our dynamic model predicts a baseline mean of 1,067 (2.5%-97.5% interval [95% I 490-2,082]) annual IDU initiations per 1,000,000 individuals, of which 886 (95% I 406-1,750) are assisted by PWID. Based on our observed statistical associations, our dynamic model predicts that increasing OAT coverage from approximately 21% to 40%, 50%, or 60% among PWID could reduce annual IDU initiations by 11.5% (95% I 2.4-21.7), 17.3% (95% I 5.6-29.4), and 22.8% (95% I 8.1-36.8) and reduce the PWID population size by 5.4% (95% I 0.1-12.0), 8.2% (95% I 2.2-16.9), and 10.9% (95% I 3.2-21.8) relative to baseline, respectively, in a decade. Less impact occurs when the protective effect of OAT is diminished, when a greater proportion of IDU initiations are unassisted by PWID, and when average IDU career length is longer. The study's main limitations are uncertainty in the causal pathway between OAT enrollment and assisting with IDU initiation and the use of a simplified model of IDU initiation. CONCLUSIONS:In addition to its known benefits on preventing HIV, hepatitis C virus (HCV), and overdose among PWID, our modeling suggests that OAT scale-up may also reduce the number of IDU initiations and PWID population size.

SUBMITTER: Marks C

PROVIDER: S-EPMC6879119 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Opioid agonist treatment scale-up and the initiation of injection drug use: A dynamic modeling analysis.

Marks Charles C Borquez Annick A Jain Sonia S Sun Xiaoying X Strathdee Steffanie A SA Garfein Richard S RS Milloy M-J MJ DeBeck Kora K Cepeda Javier A JA Werb Dan D Martin Natasha K NK

PLoS medicine 20191126 11

<h4>Background</h4>Injection drug use (IDU) is associated with multiple health harms. The vast majority of IDU initiation events (in which injection-naïve persons first adopt IDU) are assisted by a person who injects drugs (PWID), and as such, IDU could be considered as a dynamic behavioral transmission process. Data suggest that opioid agonist treatment (OAT) enrollment is associated with a reduced likelihood of assisting with IDU initiation. We assessed the association between recent OAT enrol ...[more]

PMID: 31770373

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Project description:ObjectiveTo assess the association between long term prescription opioid treatment medically dispensed for non-cancer pain and the initiation of injection drug use (IDU) among individuals without a history of substance use.DesignRetrospective cohort study.SettingLarge administrative data source (containing information for about 1.7 million individuals tested for hepatitis C virus or HIV in British Columbia, Canada) with linkage to administrative health databases, including dispensations from community pharmacies.ParticipantsIndividuals age 11-65 years and without a history of substance use (except alcohol) at baseline.Main outcome measuresEpisodes of prescription opioid use for non-cancer pain were identified based on drugs dispensed between 2000 and 2015. Episodes were classified by the increasing length and intensity of opioid use (acute (lasting <90 episode days), episodic (lasting ≥90 episode days; with <90 days' drug supply and/or <50% episode intensity), and chronic (lasting ≥90 episode days; with ≥90 days' drug supply and ≥50% episode intensity)). People with a chronic episode were matched 1:1:1:1 on socioeconomic variables to those with episodic or acute episodes and to those who were opioid naive. IDU initiation was identified by a validated administrative algorithm with high specificity. Cox models weighted by inverse probability of treatment weights assessed the association between opioid use category (chronic, episodic, acute, opioid naive) and IDU initiation.Results59 804 participants (14 951 people from each opioid use category) were included in the matched cohort, and followed for a median of 5.8 years. 1149 participants initiated IDU. Cumulative probability of IDU initiation at five years was highest for participants with chronic opioid use (4.0%), followed by those with episodic use (1.3%) and acute use (0.7%), and those who were opioid naive (0.4%). In the inverse probability of treatment weighted Cox model, risk of IDU initiation was 8.4 times higher for those with chronic opioid use versus those who were opioid naive (95% confidence interval 6.4 to 10.9). In a sensitivity analysis limited to individuals with a history of chronic pain, cumulative risk for those with chronic use (3.4% within five years) was lower than the primary results, but the relative risk was not (hazard ratio 9.7 (95% confidence interval 6.5 to 14.5)). IDU initiation was more frequent at higher opioid doses and younger ages.ConclusionsThe rate of IDU initiation among individuals who received chronic prescription opioid treatment for non-cancer pain was infrequent overall (3-4% within five years) but about eight times higher than among opioid naive individuals. These findings could have implications for strategies to prevent IDU initiation, but should not be used as a reason to support involuntary tapering or discontinuation of long term prescription opioid treatment.

Project description:BackgroundAddiction treatment and harm reduction services reduce risks of death and re-infection among patients with injection drug use-associated infective endocarditis (IDU-IE), but these are not offered at many hospitals. Among hospitalized patients with IDU-IE at the two tertiary-care hospitals in the Canadian Maritimes, we aimed to identify (1) the availability of opioid agonist treatment (OAT) and sterile drug injecting equipment, and (2) indicators of potential unmet addiction care needs.MethodsRetrospective review of IDU-IE hospitalizations at Queen Elizabeth II Health Sciences Centre (Halifax, Nova Scotia) and the Saint John Regional Hospital (Saint John, New Brunswick), October 2015 -March 2017. In Halifax, there are no addiction medicine providers on staff; in Saint John, infectious diseases physicians also practice addiction medicine. Inclusion criteria were: (1) probable or definite IE as defined by the modified Duke criteria; and (2) injection drug use within the prior 3 months.ResultsWe identified 38 hospitalizations (21 in Halifax and 17 in Saint John), for 30 unique patients. Among patients with IDU-IE and untreated opioid use disorder, OAT was offered to 36% (5/14) of patients in Halifax and 100% (6/6) of patients in Saint John. Once it was offered, most patients at both sites initiated OAT and planned to continue it after discharge. In Halifax, no patients were offered sterile injecting equipment, and during five hospitalizations staff confiscated patients' own equipment. In Saint John, four patients were offered (and one was provided) injecting equipment in hospital, and during two hospitalizations staff confiscated patients' own equipment. Concerns regarding undertreated pain or opioid withdrawal were documented during 66% (25/38) of hospitalizations, and in-hospital illicit or non-medical drug use during 32% (12/38). Two patients at each site (11%; 4/38) had self-directed discharges against medical advice.ConclusionsPatients with IDU-IE in the Canadian Maritimes have unequal access to evidence-based addiction care depending on where they are hospitalized, which differs from the community-based standard of care. Indicators of potential unmet addiction care needs in hospital were common.

Project description:Background and aimsAlthough opioid agonist treatment (OAT) for opioid use disorder (OUD) is cost-effective in settings where the HIV epidemic is concentrated among people who inject drugs, OAT coverage in Ukraine remains far below internationally recommended targets. Scale-up is limited by both OAT availability and demand. This study aimed to evaluate the cost-effectiveness of a range of plausible OAT scale-up strategies in Ukraine incorporating the potential impact of treatment spillover and the real-world demand for addiction treatment.Design, setting and participantsTen-year horizon (2016-25) modeling study of opioid addiction epidemic and treatment that accommodated potential peer effects in opioid use initiation and supply-induced treatment demand in three Ukrainian cities: Kyiv, Mykolaiv and Lviv, comprising a simulated population of people at risk of and with OUD.MeasurementsIncremental cost per quality-adjusted life-year gained in the simulated population.FindingsAn estimated 12.2-, 2.4- and 13.4-fold OAT capacity increase over 2016 baseline capacity in Kyiv, Mykolaiv and Lviv, respectively, would be cost-effective at a willingness-to-pay of one per-capita gross domestic product (GDP) per quality-adjusted life-year gained. This result is robust to parametric and structural uncertainty. Even under the most ambitious capacity increase, OAT coverage (i.e. the proportion of people with OUD receiving OAT) over a 10-year modeling horizon would be 20, 11 and 17% in Kyiv, Mykolaiv and Lviv, respectively, owing to limited demand.ConclusionsIt is estimated that a substantial increase in opioid agonist treatment (OAT) capacity in three Ukrainian cities would be cost-effective for a wide range of willingness-to-pay thresholds. Even a very ambitious capacity increase, however, is unlikely to reach internationally recommended coverage levels. Further increases in coverage may be limited by demand and would require addressing existing structural barriers to OAT access.

Project description:BACKGROUND: Meiosis is the sexual reproduction process common to eukaryotes. The diploid yeast Saccharomyces cerevisiae undergoes meiosis in sporulation medium to form four haploid spores. Initiation of the process is tightly controlled by intricate networks of positive and negative feedback loops. Intriguingly, expression of early meiotic proteins occurs within a narrow time window. Further, sporulation efficiency is strikingly different for yeast strains with distinct mutations or genetic backgrounds. To investigate signal transduction pathways that regulate transient protein expression and sporulation efficiency, we develop a mathematical model using ordinary differential equations. The model describes early meiotic events, particularly feedback mechanisms at the system level and phosphorylation of signaling molecules for regulating protein activities. RESULTS: The mathematical model is capable of simulating the orderly and transient dynamics of meiotic proteins including Ime1, the master regulator of meiotic initiation, and Ime2, a kinase encoded by an early gene. The model is validated by quantitative sporulation phenotypes of single-gene knockouts. Thus, we can use the model to make novel predictions on the cooperation between proteins in the signaling pathway. Virtual perturbations on feedback loops suggest that both positive and negative feedback loops are required to terminate expression of early meiotic proteins. Bifurcation analyses on feedback loops indicate that multiple feedback loops are coordinated to modulate sporulation efficiency. In particular, positive auto-regulation of Ime2 produces a bistable system with a normal meiotic state and a more efficient meiotic state. CONCLUSIONS: By systematically scanning through feedback loops in the mathematical model, we demonstrate that, in yeast, the decisions to terminate protein expression and to sporulate at different efficiencies stem from feedback signals toward the master regulator Ime1 and the early meiotic protein Ime2. We argue that the architecture of meiotic initiation pathway generates a robust mechanism that assures a rapid and complete transition into meiosis. This type of systems-level regulation is a commonly used mechanism controlling developmental programs in yeast and other organisms. Our mathematical model uncovers key regulations that can be manipulated to enhance sporulation efficiency, an important first step in the development of new strategies for producing gametes with high quality and quantity.

Project description:BackgroundInjecting-related bacterial and fungal infections are associated with significant morbidity and mortality among people who inject drugs (PWID), and they are increasing in incidence. Following hospitalization with an injecting-related infection, use of opioid agonist treatment (OAT; methadone or buprenorphine) may be associated with reduced risk of death or rehospitalization with an injecting-related infection.Methods and findingsData came from the Opioid Agonist Treatment Safety (OATS) study, an administrative linkage cohort including all people in New South Wales, Australia, who accessed OAT between July 1, 2001 and June 28, 2018. Included participants survived a hospitalization with injecting-related infections (i.e., skin and soft-tissue infection, sepsis/bacteremia, endocarditis, osteomyelitis, septic arthritis, or epidural/brain abscess). Outcomes were all-cause death and rehospitalization for injecting-related infections. OAT exposure was classified as time varying by days on or off treatment, following hospital discharge. We used separate Cox proportional hazards models to assess associations between each outcome and OAT exposure. The study included 8,943 participants (mean age 39 years, standard deviation [SD] 11 years; 34% women). The most common infections during participants' index hospitalizations were skin and soft tissue (7,021; 79%), sepsis/bacteremia (1,207; 14%), and endocarditis (431; 5%). During median 6.56 years follow-up, 1,481 (17%) participants died; use of OAT was associated with lower hazard of death (adjusted hazard ratio [aHR] 0.63, 95% confidence interval [CI] 0.57 to 0.70). During median 3.41 years follow-up, 3,653 (41%) were rehospitalized for injecting-related infections; use of OAT was associated with lower hazard of these rehospitalizations (aHR 0.89, 95% CI 0.84 to 0.96). Study limitations include the use of routinely collected administrative data, which lacks information on other risk factors for injecting-related infections including injecting practices, injection stimulant use, housing status, and access to harm reduction services (e.g., needle exchange and supervised injecting sites); we also lacked information on OAT medication dosages.ConclusionsFollowing hospitalizations with injection drug use-associated bacterial and fungal infections, use of OAT is associated with lower risks of death and recurrent injecting-related infections among people with opioid use disorder.

Project description:BACKGROUND:Patients recovering from opioid use disorders (OUD) may be prone to relapse and opioid misuse in the postoperative period due to re-exposure to prescription opioids for pain control. This retrospective study analyzed the incidence of confirmed opioid misuse in the postoperative period in patients with OUDs enrolled in an opioid agonist treatment (OAT) program. METHODS:The study population was US veterans with a diagnosis of OUD who enrolled in the OAT program at VA Maryland Health Care System (Baltimore, Maryland, USA) between 1/1/2000 and 12/31/2016. The patients were excluded if they were enrolled in OAT for less than a year, or if they had surgery within the first 180 days after OAT admission. The surgical group consisted of veterans who had surgery or an invasive procedure during their enrollment in the OAT program. The control (reference) group consisted of enrolled veterans who did not have any invasive procedure. The primary outcome was the first opioid misuse within 365?days after surgery date in the surgical group or a randomly assigned sham surgery date in controls. Opioid misuse was defined as either inappropriate use of opioids detected via urinalysis or admission with a diagnosis of an opioid overdose. RESULTS:From a total of 1352 patients enrolled in the OAT program, 413 were excluded because they were enrolled for less than a year, and 26 were excluded because they had surgery within the first 180?days after admission to the OAT program. Of the 923 eligible patients, 87 had surgery while enrolled and 836 did not. Using propensity scores, all 87 of the surgical cases were matched to 249 of the control cases. In the matched groups, surgery was positively associated with postoperative opioid misuse (odds ratio (OR) of 1.91, 95% CI 1.05-3.48, p?=?0.034) in logistic regression. CONCLUSION:Among patients with a history of opioid use disorders, the postoperative period was associated with an increased risk of opioid misuse. Moreover, opioid misuse among patients in an opioid agonist treatment program may well be considered a surgical hazard.

Dataset Information

Opioid agonist treatment scale-up and the initiation of injection drug use: A dynamic modeling analysis.

Publications

Opioid agonist treatment scale-up and the initiation of injection drug use: A dynamic modeling analysis.

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