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The International Journal on Drug Policy Dec 2019Canada and the United States (U.S.) face an opioid use disorder (OUD) and opioid overdose epidemic. The most effective OUD treatment is opioid agonist therapy... (Comparative Study)
Comparative Study
Canada and the United States (U.S.) face an opioid use disorder (OUD) and opioid overdose epidemic. The most effective OUD treatment is opioid agonist therapy (OAT)-buprenorphine (with and without naloxone) and methadone. Although federal approval for OAT occurred decades ago, in both countries, access to and use of OAT is low. Restrictive policies and complex regulations contribute to limited OAT access. Through a non-systematic literature scan and a review of publicly available policy documents, we examined and compared OAT policies and practice at the federal (Canada vs. U.S.) and local levels (British Columbia [B.C.] vs. Oregon). Differences and similarities were noted between federal and local OAT policies, and subsequently OAT access. In Canada, OAT policy control has shifted from federal to provincial authorities. Conversely, in the U.S., federal authorities maintain primary control of OAT regulations. Local OAT health insurance coverage policies were substantively different between B.C. and Oregon. In B.C., five OAT options were available, while in Oregon, only two OAT options were available with administrative limitations. The differences in local OAT access and coverage policies between B.C. and Oregon, may be explained, in part, to the differences in Canadian and U.S. federal OAT policies, specifically, the relaxation of special federal OAT regulatory controls in Canada. The analysis also highlights the complicating contributions, and likely policy solutions, that exist within other drug policy sub-domains (e.g., the prescription regime, and drug control regime) and broader policy domains (e.g., constitutional rights). U.S. policymakers and health officials could consider adopting Canada's regulatory policy approach to expand OAT access to mitigate the harms of the ongoing opioid overdose epidemic.
Topics: Buprenorphine; Canada; Drug Overdose; Health Policy; Humans; Insurance Coverage; Methadone; Naloxone; Opiate Substitution Treatment; Opioid Epidemic; Opioid-Related Disorders; United States
PubMed: 30765118
DOI: 10.1016/j.drugpo.2019.01.020 -
Pharmaceutical Medicine Aug 2022Comparator selection is an important consideration in the design of observational research studies that evaluate potential associations between drug therapies and... (Observational Study)
Observational Study
BACKGROUND
Comparator selection is an important consideration in the design of observational research studies that evaluate potential associations between drug therapies and adverse event risks. It can affect the validity of observational study results, and potentially impact data interpretation, regulatory decision making, and patient medication access.
OBJECTIVE
The aim of this study was to assess the impact of comparator selection bias using two real-world case studies evaluating an increased rate of acute myocardial infarction (AMI).
METHODS
Data from the Truven Health Analytics MarketScan electronic medical claims database were used to conduct two retrospective observational cohort studies, utilizing a cohort new-user design, comparing AMI risk between testosterone replacement therapy (TRT) and phosphodiesterase-5 inhibitors (PDE5is) in men treated for hypogonadism, and triptans versus other prescribed acute treatments for migraine in adults. All patients were enrolled continuously in a health plan (no enrollment gap > 31 consecutive days) for ≥ 1 year before index. Baseline period was defined as 365 days prior to index. Exposure was defined by prescription and outcome of interest was defined as occurrence of AMI. Using Cox proportional hazard models, primary analysis for the TRT cohort compared AMI risk between propensity score (PS)-matched TRT-treated and untreated patients; secondary analysis evaluated risk between PS-matched TRT-treated and PDE5i-treated patients. For the triptan cohort, primary analysis compared AMI/ischemic stroke risk between PS-matched triptan-treated and opiate-treated patients; secondary analysis evaluated risk between PS-matched triptan-treated and nonsteroidal anti-inflammatory drug (NSAID)-treated patients and PS-matched non-prescription-treated migraine patients and general patients.
RESULTS
No significant association between TRT and AMI was observed among TRT-treated (N = 198,528, mean age 52.4 ± 11.4 years) versus PDE5i-treated men (N = 198,528, mean age 52.3 ± 11.5 years) overall (adjusted hazard ratio [aHR] 1.01; 95% CI 0.95-1.07; p = 0.80). Among patients with prior cardiovascular disease (CVD), risk of AMI was significantly increased for TRT-treated versus PDE5i-treated patients (aHR 1.13; 95% CI 1.03-1.25). The triptan study included three comparisons (triptans [N = 436,642] vs prescription NSAIDs [N = 334,152], opiates [N = 55,234], and untreated migraine [N = 1,168,212]), and a positive control (untreated vs general non-migraine patients [N = 11,735,009]). Analyses of MI risk in migraine patients prescribed triptans versus NSAIDs/opiates had mixed results: the point estimate ranged from 0.33 to 0.84 depending on chosen study window.
CONCLUSIONS
Cardiovascular outcomes were not worse in hypogonadism patients with TRT versus PDE5i; however, a potential association with AMI was found in patients with prior CVD receiving TRT versus PDE5i. Findings pointed to a pseudo-protective effect of triptans versus untreated migraine patients or those potentially older and less healthy patients exposed to prescription NSAIDs or opiates. Triptan users should not be compared with those using other anti-migraine prescriptions when evaluating cardiovascular outcomes in migraine patients. Presence of high cardiovascular risks may contribute to channeling bias-healthier subjects being selected to receive treatment-highlighting the importance of choosing comparators wisely in observational studies.
Topics: Adult; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Cardiovascular Diseases; Heart Disease Risk Factors; Humans; Hypogonadism; Male; Middle Aged; Migraine Disorders; Myocardial Infarction; Opiate Alkaloids; Retrospective Studies; Risk Factors; Serotonin 5-HT1 Receptor Agonists; Tryptamines
PubMed: 35788962
DOI: 10.1007/s40290-022-00433-z -
Molecules (Basel, Switzerland) Jan 2022Drug abuse still represents a global problem, and it is associated with an increased risk of diseases, injuries, and deaths. Cocaine (COC) and opiates are the most...
Drug abuse still represents a global problem, and it is associated with an increased risk of diseases, injuries, and deaths. Cocaine (COC) and opiates are the most abused drugs and account for a significant number of fatalities. Therefore, it is important to develop methods capable of effectively identifying and quantifying these substances. The present study aims to evaluate the long-term stability of COC, ecgonine methylester (EME), benzoylecgonine (BEG), cocaethylene (COET), norcocaine (NCOC), morphine (MOR), codeine (COD) and 6-monoacetylmorphine (6-MAM) in oral fluid samples. The analytes of interest were isolated from the matrix (50 µL) using the dried saliva spots (DSS) sampling approach and were subsequently analyzed by gas chromatography coupled with tandem mass spectrometry (GC-MS/MS). The parameters that could influence the stability of the target compounds were studied, and these were storage temperature, light, use of preservatives (and respective concentrations), and time. The effects of each parameter were evaluated using the design of experiments (DOE) approach. The stability of the target analytes was improved when the DSS were stored at room temperature, in the presence of light and using 1% sodium fluoride. The best conditions were then adopted for the DSS storage and long-term stability was assessed. COD was only stable for 1 day, EME was stable for 3 days, COC, COET, NCOC and 6-MAM were stable for 7 days, MOR for 14 days and BEG remained stable throughout the study (136 days). This is the first study that evaluates the stability of these compounds in oral fluid samples after application in DSS cards, and optimizes the conditions in order to improve their stability.
Topics: Cocaine; Gas Chromatography-Mass Spectrometry; Narcotics; Opiate Alkaloids; Saliva; Tandem Mass Spectrometry
PubMed: 35163906
DOI: 10.3390/molecules27030641 -
JAMA Network Open May 2022As opioid-related deaths continue to climb, methods to reduce barriers to prescribing buprenorphine for individuals with opioid use disorder (OUD) are needed. Recent...
IMPORTANCE
As opioid-related deaths continue to climb, methods to reduce barriers to prescribing buprenorphine for individuals with opioid use disorder (OUD) are needed. Recent conversations by state and federal authorities targeting low-threshold buprenorphine aim to reduce some barriers to prescribing buprenorphine; however, what remains unclear is whether removal of the requirement to obtain a waiver for prescribing buprenorphine through the Drug Addiction Treatment Act of 2000 (an X-waiver) will be enough to increase access to buprenorphine.
OBJECTIVE
To assess barriers and facilitators of obtaining an X-waiver and prescribing buprenorphine.
DESIGN, SETTING, AND PARTICIPANTS
This mixed-method survey study was conducted between September and December 2020; 607 office-based Texas clinicians were surveyed after they attended a buprenorphine X-waiver training course. All attendees between March 2, 2019, and February 28, 2020, were eligible to receive this survey; 126 responses were received (20% response rate: 81 physicians, 37 nurse practitioners, and 8 physician assistants). Data analysis was performed October 2021.
MAIN OUTCOMES AND MEASURES
Surveys measured the extent to which clinicians experienced 9 previously identified barriers during the waiver process and in prescribing buprenorphine. The survey included open-ended items assessing facilitating factors to obtaining a waiver and to prescribing buprenorphine for OUD. The barriers were analyzed using χ2 tests of homogeneity. Qualitative data were analyzed using a constant comparative method.
RESULTS
Among 126 clinicians who responded, 61 (48.4%) had received an X-waiver; of these waivered clinicians, 22 (36%) were prescribing buprenorphine and 39 (64%) were not. "Complexity of X-waiver process," "Perceived lack of professional support and referral network," and "Getting started" were significantly different barriers among waivered and nonwaivered clinicians. Significant differences in barriers experienced between prescribers and nonprescribers were "Getting started" and "Accessing reimbursement for treatment." The most frequently mentioned facilitators involved changes to the waiver training and the need for networks connecting experienced clinicians with those in the initial stages of readiness for prescribing buprenorphine for OUD.
CONCLUSIONS AND RELEVANCE
This survey study's results contribute new understanding of facilitators to obtaining the X-waiver and to prescribing buprenorphine. Furthermore, these findings suggest that to increase access to compassionate evidence-based treatment for OUD, clinicians need ongoing support and mentorship from experienced and knowledgeable clinicians. Interventions aimed at improving access to buprenorphine should focus on facilitating such networks to increase the number of clinicians who obtain an X-waiver and prescribe buprenorphine for OUD.
Topics: Analgesics, Opioid; Buprenorphine; Humans; Opiate Substitution Treatment; Opioid-Related Disorders; Physician Assistants
PubMed: 35552721
DOI: 10.1001/jamanetworkopen.2022.12419 -
Drug Testing and Analysis Oct 2022Quantitative analysis of postmortem urine, instead of blood, for buprenorphine and metabolites may provide additional evidence for the diagnosis of fatal buprenorphine...
Quantitative analysis of postmortem urine, instead of blood, for buprenorphine and metabolites may provide additional evidence for the diagnosis of fatal buprenorphine poisoning. In this study, 247 autopsy urine samples, previously testing positive for buprenorphine or norbuprenorphine, were quantitatively reanalysed with a recently developed liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for unconjugated buprenorphine (BUP), norbuprenorphine (NBUP), naloxone (NAL), and their respective conjugated metabolites, buprenorphine glucuronide (BUPG), norbuprenorphine glucuronide (NBUPG), and naloxone glucuronide (NALG). The cases were divided, according to medical examiners' decision, to buprenorphine poisonings and other causes of death. The groups were compared for urinary concentrations and metabolite concentration ratios of the six analytes. All median concentrations were higher in the buprenorphine poisoning group. The median concentration of BUPG was significantly higher and the median metabolite ratios NBUP/BUP, NBUPG/BUPG, and NBUPtotal/BUPtotal were significantly lower in poisonings than in other causes of death. Naloxone-related concentrations and ratios were not significantly different between the groups.
Topics: Buprenorphine; Chromatography, Liquid; Glucuronides; Naloxone; Tandem Mass Spectrometry
PubMed: 35834288
DOI: 10.1002/dta.3347 -
Substance Use & Misuse 2022Illicit opioid use in pregnancy is associated with adverse maternal, neonatal, and childhood outcomes. Opioid substitution is recommended, but whether methadone or... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Illicit opioid use in pregnancy is associated with adverse maternal, neonatal, and childhood outcomes. Opioid substitution is recommended, but whether methadone or buprenorphine is the optimal agent remains unclear.
METHODS
We searched EMBASE, PubMed, Web of Science, Scopus, Open Gray, CINAHL and the Cochrane Central Registry of Controlled Trials (CENTRAL) from inception to April 2020 for randomized controlled trials (RCTs) and cohort studies comparing methadone and buprenorphine treatment for opioid-using mothers. Included studies assessed maternal and or neonatal outcomes. We used random-effects meta-analyses to estimate summary measures for outcomes and report these separately for RCTs and cohort studies.
RESULTS
Of 408 abstracts screened, 20 papers were included (4 RCTs, 16 cohort, 223 and 7028 participants respectively). All RCTs (4/4) had a high risk of bias and median (IQR) Newcastle Ottawa Scale for cohort studies was 7.5 (6-9). In both RCTs and cohort studies, buprenorphine was associated with; greater offspring birth weight (weighted mean difference [WMD] 343 g (95% CI: 40-645 g) in RCT and 184 g (95% CI: 121-247 g) in cohort studies); body length at birth (WMD 2.28 cm (95% CI: 1.06-3.49 cm) in RCTs and 0.65 cm (95% CI: 0.31-0.98 cm) in cohort studies); and reduced risk of prematurity (risk ratio [RR] 0.41 (95% CI: 0.18-0.93) in RCTs and 0.63 [95% CI: 0.53-0.75] in cohort studies) when compared to methadone. All other clinical outcomes were comparable.
CONCLUSIONS
Compared to methadone, buprenorphine was consistently associated with improved birthweight and gestational age, however given potential biases, results should be interpreted with caution.
Topics: Analgesics, Opioid; Buprenorphine; Child; Female; Humans; Infant, Newborn; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy
PubMed: 35758300
DOI: 10.1080/10826084.2022.2083174 -
The Journal of Pharmacology and... Aug 2021Opioid use disorder (OUD) is a major socioeconomic burden. An ideal OUD pharmacotherapy will mitigate the suffering associated with opioid-withdrawal, inhibit the...
Opioid use disorder (OUD) is a major socioeconomic burden. An ideal OUD pharmacotherapy will mitigate the suffering associated with opioid-withdrawal, inhibit the effects of high efficacy opioids, and minimize opioid-cravings while being safe and accessible to a diverse patient population. Although current OUD pharmacotherapies inhibit the euphoric effects of opioids of abuse, the extent to which they safely alleviate withdrawal and opioid-cravings corresponds with their intrinsic opioid receptor (MOR) efficacy. In addition to inhibiting the euphoric effects of opioids of abuse, the medium efficacy MOR agonist buprenorphine alleviates withdrawal and opioid-cravings, but its intrinsic MOR efficacy is sufficient such that its utility is limited by abuse and safety liabilities. Although the MOR antagonist naltrexone minimizes euphoria and has no abuse liability, it exacerbates suffering associated with withdrawal and opioid cravings. Therefore, a therapeutic with intrinsic MOR activity between the partial agonist (buprenorphine) and the antagonist (naltrexone) would strike a balance between the benefits and liabilities of these two therapeutics. To address this need, we derived RM1490, an MOR agonist based on a nonmorphinan scaffold that exhibits approximately half the intrinsic MOR efficacy of buprenorphine. In a series of preclinical assays, we compared RM1490 with buprenorphine and naltrexone at doses that achieve therapeutic levels of central nervous system MOR occupancy. RM1490 exhibited a behavioral profile consistent with reduced reward, dependence, and precipitated withdrawal liabilities. RM1490 was also more effective than buprenorphine at reversing the respiratory depressant effects of fentanyl and did not suppress respiration when combined with diazepam. SIGNIFICANCE STATEMENT: In preclinical studies, RM1490 has a physiological and behavioral profile suitable for opioid use disorder maintenance therapy.
Topics: Buprenorphine; Naltrexone; Opioid-Related Disorders
PubMed: 34011529
DOI: 10.1124/jpet.120.000214 -
Annals of Emergency Medicine Dec 2021We retrospectively evaluated the implementation of low-threshold emergency department (ED) buprenorphine treatment at 52 hospitals participating in the CA Bridge Program...
STUDY OBJECTIVE
We retrospectively evaluated the implementation of low-threshold emergency department (ED) buprenorphine treatment at 52 hospitals participating in the CA Bridge Program using the RE-AIM (reach, effectiveness, adoption, implementation, maintenance) framework.
METHODS
The CA Bridge model included low-threshold buprenorphine, connection to outpatient care, and harm reduction. Implementation began in March 2019. Participating hospitals reported aggregated clinical data monthly after program initiation. Outcomes included identification of opioid use disorder, buprenorphine administration, and linkage to outpatient addiction treatment. Multivariable models assessed associations between hospital location (rural versus urban) and teaching status (clinical teaching hospital versus community hospital) and outcomes in adopting the CA Bridge Program.
RESULTS
Reach: A diverse and geographically distributed group of 52 California hospitals were enrolled in 2 phases (March and August 2019); 12 (23%) were rural and 13 (25%) were teaching hospitals. Effectiveness: Over a 14-month implementation period, 12,009 opioid use disorder patient encounters were identified, including 7,179 (59.7%) where buprenorphine was administered and 4,818 (40.1%) where follow-up visits were attended. Adoption: In multivariable analysis, adoption did not differ significantly between rural and urban or teaching and nonteaching hospitals.
IMPLEMENTATION
By program completion, all 52 (100%) hospitals treated opioid use disorder with buprenorphine; 45 (86.5%) administered buprenorphine after naloxone reversal; 41 (84.6%) offered buprenorphine for inpatients; 48 (92.3%) initiated buprenorphine in pregnant women; and 29 (55.8%) offered take-home naloxone. Maintenance: At 8-month follow-up, all 52 sites reported continued buprenorphine treatment.
CONCLUSION
Low-threshold ED buprenorphine treatment implemented with a harm reduction approach and active navigation to outpatient addiction treatment was successful in achieving buprenorphine treatment for opioid use disorder in diverse California communities.
Topics: Adult; Buprenorphine; California; Emergency Service, Hospital; Female; Hospitals, Teaching; Humans; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Retrospective Studies
PubMed: 34353655
DOI: 10.1016/j.annemergmed.2021.05.024 -
American Journal of Preventive Medicine Nov 2022Expanding access to medications for opioid use disorder is a cornerstone to addressing the opioid overdose epidemic. However, recent research suggests that the...
INTRODUCTION
Expanding access to medications for opioid use disorder is a cornerstone to addressing the opioid overdose epidemic. However, recent research suggests that the distribution of medications for opioid use disorder has been inequitable. This study analyzes the racial‒ethnic disparities in the receipt of medications for opioid use disorder among Medicaid patients diagnosed with opioid use disorder.
METHODS
Medicaid claims data from the Transformed Medicaid Statistical Information System for the years 2017-2019 were used for the analysis. Logistic regression models estimated the odds of receiving buprenorphine and Vivitrol within 180 days after initial opioid use disorder diagnosis on the basis of race‒ethnicity. Analysis was conducted in 2022.
RESULTS
Non-Hispanic Black people, non-Hispanic American Indian or Alaskan Native/Asian/Hawaiian/Pacific Islander people, and Hispanic people had 42%, 12%, and 22% lower odds of buprenorphine receipt and 47%, 12%, and 20% lower odds of Vivitrol receipt, respectively, than non-Hispanic White people, controlling for clinical and demographic patient variables.
CONCLUSIONS
This study suggests that there are racial‒ethnic disparities in the receipt of buprenorphine and Vivitrol among Medicaid patients diagnosed with opioid use disorder after adjusting for demographic, geographic, and clinical characteristics. The potential strategies to address these disparities include expanding the workforce of providers who can prescribe medications for opioid use disorder in low-income communities and communities of color and allocating resources to address the stigma in medications for opioid use disorder treatment.
Topics: United States; Humans; Buprenorphine; Medicaid; Opiate Substitution Treatment; Ethnicity; Opioid-Related Disorders; Analgesics, Opioid
PubMed: 35803789
DOI: 10.1016/j.amepre.2022.05.006 -
JAMA Network Open Apr 2022Given that COVID-19 and recent natural disasters exacerbated the shortage of medication for opioid use disorder (MOUD) services and were associated with increased opioid...
IMPORTANCE
Given that COVID-19 and recent natural disasters exacerbated the shortage of medication for opioid use disorder (MOUD) services and were associated with increased opioid overdose mortality, it is important to examine how a community's ability to respond to natural disasters and infectious disease outbreaks is associated with MOUD access.
OBJECTIVE
To examine the association of community vulnerability to disasters and pandemics with geographic access to each of the 3 MOUDs and whether this association differs by urban, suburban, or rural classification.
DESIGN, SETTING, AND PARTICIPANTS
This cross-sectional study of zip code tabulation areas (ZCTAs) in the continental United States excluding Washington, DC, conducted a geospatial analysis of 2020 treatment location data.
EXPOSURES
Social vulnerability index (US Centers for Disease Control and Prevention measure of vulnerability to disasters or pandemics).
MAIN OUTCOMES AND MEASURES
Drive time in minutes from the population-weighted center of the ZCTA to the ZCTA of the nearest treatment location for each treatment type (buprenorphine, methadone, and extended-release naltrexone).
RESULTS
Among 32 604 ZCTAs within the continental US, 170 within Washington, DC, and 20 without an urban-rural classification were excluded, resulting in a final sample of 32 434 ZCTAs. Greater social vulnerability was correlated with longer drive times for methadone (correlation, 0.10; 95% CI, 0.09 to 0.11), but it was not correlated with access to other MOUDs. Among rural ZCTAs, increasing social vulnerability was correlated with shorter drive times to buprenorphine (correlation, -0.10; 95% CI, -0.12 to -0.08) but vulnerability was not correlated with other measures of access. Among suburban ZCTAs, greater vulnerability was correlated with both longer drive times to methadone (correlation, 0.22; 95% CI, 0.20 to 0.24) and extended-release naltrexone (correlation, 0.15; 95% CI, 0.13 to 0.17).
CONCLUSIONS AND RELEVANCE
In this study, communities with greater vulnerability did not have greater geographic access to MOUD, and the mismatch between vulnerability and medication access was greatest in suburban communities. Rural communities had poor geographic access regardless of vulnerability status. Future disaster preparedness planning should match the location of services to communities with greater vulnerability to prevent inequities in overdose deaths.
Topics: Analgesics, Opioid; Buprenorphine; Cross-Sectional Studies; Health Services Accessibility; Humans; Methadone; Naltrexone; Opiate Substitution Treatment; Opioid-Related Disorders; United States; COVID-19 Drug Treatment
PubMed: 35438757
DOI: 10.1001/jamanetworkopen.2022.7028