The role of prescription opioid and cannabis supply policies on opioid overdose deaths.

Mandatory prescription drug monitoring programs and cannabis legalization have been hypothesized to reduce overdose deaths. We examined associations between prescription monitoring programs with access mandates ("must-query PDMPs"), legalization of medical and recreational cannabis supply, and opioid overdose deaths in United States counties in 2013-2020. Using data on overdose deaths from the National Vital Statistics System, we fit Bayesian spatiotemporal models to estimate risk differences and 95% credible intervals (CrI) in county-level opioid overdose deaths associated with enactment of these state policies. Must-query PDMPs were independently associated with on average 0.8 (95% CrI: 0.5, 1.0) additional opioid-involved overdose deaths per 100,000 person-years. Legal cannabis supply was not independently associated with opioid overdose deaths in this time period. Must-query PDMPs enacted in the presence of legal (medical or recreational) cannabis supply were associated with 0.7 (95% CrI: 0.4, 0.9) more opioid-involved deaths, relative to must-query PDMPs without any legal cannabis supply. In a time when overdoses are driven mostly by non-prescribed opioids, stricter opioid prescribing policies and more expansive cannabis legalization were not associated with reduced overdose death rates.

The Combined Relationship of Prescription Drug Monitoring Program Enactment and Medical Cannabis Laws with Chronic Pain-Related Healthcare Visits.

BACKGROUND: U.S. state electronic prescription drug monitoring programs (PDMPs) are associated with reduced opioid dispensing among people with chronic pain and may impact use of other chronic pain treatments. In states with medical cannabis laws (MCLs), patients can use cannabis for chronic pain management, reducing their need for chronic-pain related treatment visits and moderating effects of PDMP laws. OBJECTIVE: Given high rates of chronic pain among Medicaid enrollees, we examined associations between PDMP enactment in the presence or absence of MCL on chronic pain-related outpatient and emergency department (ED) visits. DESIGN: We created annual cohorts of Medicaid enrollees with chronic pain diagnoses using national Medicaid claims data from 2002-2013 and 2016. Negative binomial hurdle models produced adjusted odds ratios (aOR) for the likelihood of any chronic pain-related outpatient or ED visit and incident rate ratios (IRR) for the rate of visits among patients with ≥ 1 visit. PARTICIPANTS: Medicaid enrollees aged 18-64 years with chronic pain (N = 4,878,462). MAIN MEASURES: A 3-level state-year variable with the following categories: 1) no PDMP, 2) PDMP enactment in the absence of MCL, or 3) PDMP enactment in the presence of MCL. Healthcare codes for chronic pain-related outpatient and ED visits each year. KEY RESULTS: The sample was primarily female (67.2%), non-Hispanic White (51.2%), and ages 40-55 years (37.2%). Compared to no-PDMP states, PDMP enactment in the absence of MCL was not associated with chronic pain-related outpatient visits but PDMP enactment in the presence of MCL was associated with lower odds of chronic pain-related outpatient visits (aOR = 0.81, 95% CI:0.71-0.92). PDMP enactment was not associated with ED visits, irrespective of MCL. CONCLUSIONS: During a period of PDMP and MCL expansion, our findings suggest treatment shifts for persons with chronic pain away from outpatient settings, potentially related to increased use of cannabis for chronic pain management.

Prescribing Syringes to People Who Inject Drugs: Advancing Harm Reduction in Primary Care.

Access to new syringes can reduce the risk of HIV and hepatitis C transmission, skin and soft tissue infections, and infectious endocarditis for people who inject drugs (PWID). Syringe service programs (SSPs) and other harm reduction programs are a good source of syringes. However, they are sometimes not accessible due to limited hours, geographic barriers, and other factors. In this perspective, we argue that when PWID faces barriers to syringes physicians and other providers should prescribe, and pharmacists should dispense, syringes to decrease health risks associated with syringe re-use. This strategy is endorsed by professional organizations and is legally permissible in most states. Such prescribing has numerous benefits, including insurance coverage of the cost of syringes and the sense of legitimacy conveyed by a prescription. We discuss these benefits as well as the legality of prescribing and dispensing syringes and address practical considerations such as type of syringe, quantity, and relevant diagnostic codes, if required. In the face of an unprecedented overdose crisis with many associated health harms, we also make the case for advocacy to change state and federal laws to make access to prescribed syringes uniform, smooth, and universal as part of a suite of harm reduction efforts.

Effects of Opioid Prescribing Cap Laws on Opioid and Other Pain Treatments Among Persons with Chronic Pain.

BACKGROUND: Many states have adopted laws that limit the amount or duration of opioid prescriptions. These limits often focus on prescriptions for acute pain, but there may be unintended consequences for those diagnosed with chronic pain, including reduced opioid prescribing without substitution of appropriate non-opioid treatments. OBJECTIVE: To evaluate the effects of state opioid prescribing cap laws on opioid and non-opioid treatment among those diagnosed with chronic pain. DESIGN: We used a difference-in-differences approach that accounts for staggered policy adoption. Treated states included 32 states that implemented a prescribing cap law between 2017 and 2019. POPULATION: A total of 480,856 adults in the USA who were continuously enrolled in medical and pharmacy coverage from 2013 to 2019 and diagnosed with a chronic pain condition between 2013 and 2016. MAIN MEASURES: Among individuals with chronic pain in each state: proportion with at least one opioid prescription and with prescriptions of a specific duration or dose, average number of opioid prescriptions, average opioid prescription duration and dose, proportion with at least one non-opioid chronic pain prescription, average number of such prescriptions, proportion with at least one chronic pain procedure, and average number of such procedures. KEY RESULTS: State laws limiting opioid prescriptions were not associated with changes in opioid prescribing, non-opioid medication prescribing, or non-opioid chronic pain procedures among patients with chronic pain diagnoses. CONCLUSIONS: These findings do not support an association between state opioid prescribing cap laws and changes in the treatment of chronic non-cancer pain.

Persistent Criminalization and Structural Racism in US Drug Policy: The Case of Overdose Good Samaritan Laws.

The US overdose crisis continues to worsen and is disproportionately harming Black and Hispanic/Latino people. Although the "War on Drugs" continues to shape drug policy-at the disproportionate expense of Black and Hispanic/Latino people-states have taken some steps to reduce War on Drugs-related harms and adopt a public health-centered approach. However, the rhetoric regarding these changes has, in many cases, outstripped reality. Using overdose Good Samaritan Laws (GSLs) as a case study, we argue that public health-oriented policy changes made in some states are undercut by the broader enduring environment of a structurally racist drug criminalization agenda that continues to permeate and constrict most attempts at change. Drawing from our collective experiences in public health research and practice, we describe 3 key barriers to GSL effectiveness: the narrow parameters within which they apply, the fact that they are subject to police discretion, and the passage of competing laws that further criminalize people who use illicit drugs. All reveal a persisting climate of drug criminalization that may reduce policy effectiveness and explain why current reforms may be destined for failure and further disadvantage Black and Hispanic/Latino people who use drugs. (Am J Public Health. 2023;113(S1):S43-S48. https://doi.org/10.2105/AJPH.2022.307037).

Statewide Policy to Increase Provision of Take-Home Naloxone at Emergency Department Visits for Opioid Overdose, Rhode Island, 2018‒2019.

In 2017, Rhode Island responded to rising overdose deaths by establishing statewide emergency department (ED) treatment standards for opioid overdose and opioid use disorder. One requirement of the policy is that providers prescribe or provide take-home naloxone to anyone presenting to EDs with opioid overdose. Among adults presenting to EDs with opioid overdose from 2018 to 2019, approximately half received take-home naloxone. Receipt of naloxone was associated with administration of naloxone before ED presentation, ED policy certification level, and regional overdose frequency. (Am J Public Health. 2023;113(4):372-377. https://doi.org/10.2105/AJPH.2022.307213).

Effects of state opioid prescribing cap laws on providers' opioid prescribing patterns among patients with chronic non-cancer pain.

Prior work suggests opioid prescribing cap laws are not associated with changes in opioid prescribing among patients with chronic pain. It is unknown how these effects differ by provider specialty, provider opioid prescribing volume, or patient insurer. This study assessed effects of state opioid prescribing cap laws on opioid prescribing among providers of patients with chronic non-cancer pain, by high volume prescribing, provider specialty, and patient insurer. We identified 224,290 providers of patients with low back pain, fibromyalgia, or headache from the IQVIA administrative database. Using a difference-in-differences approach, we examined impacts of opioid prescribing cap laws implemented between 2016 and 2018 on the annual proportion of a provider's patient panel who received any opioid prescription, as well as on dose and duration of opioid prescriptions. For providers overall, high volume prescribers, all specialties, and patient insurance categories, prescribing cap laws were associated with non-significant changes of <1.0, 1.5, and 3.5 percentage points in the proportion of chronic non-cancer patients receiving any opioid prescription, a prescription with 7 days' supply, or with >50 morphine milligram equivalents (MME)/day, per year, respectively. There were two exceptions with high dose prescribing: prescribing cap laws were associated with a 1.5 percentage point increase in the proportion of high-volume prescribers' patient panel receiving an opioid prescription with ≥50 MME/day, and a 3.0 percentage point decrease in the same measure among surgeons. Among nearly all measured subgroups of providers and patient insurers, opioid prescribing cap laws were not associated with changes in opioid prescribing.

Evidence of an Absence of Inbreeding Depression in a Wild Population of Weddell Seals (Leptonychotes weddellii).

Inbreeding depression can reduce the viability of wild populations. Detecting inbreeding depression in the wild is difficult; developing accurate estimates of inbreeding can be time and labor intensive. In this study, we used a two-step modeling procedure to incorporate uncertainty inherent in estimating individual inbreeding coefficients from multilocus genotypes into estimates of inbreeding depression in a population of Weddell seals (Leptonychotes weddellii). The two-step modeling procedure presented in this paper provides a method for estimating the magnitude of a known source of error, which is assumed absent in classic regression models, and incorporating this error into inferences about inbreeding depression. The method is essentially an errors-in-variables regression with non-normal errors in both the dependent and independent variables. These models, therefore, allow for a better evaluation of the uncertainty surrounding the biological importance of inbreeding depression in non-pedigreed wild populations. For this study we genotyped 154 adult female seals from the population in Erebus Bay, Antarctica, at 29 microsatellite loci, 12 of which are novel. We used a statistical evidence approach to inference rather than hypothesis testing because the discovery of both low and high levels of inbreeding are of scientific interest. We found evidence for an absence of inbreeding depression in lifetime reproductive success, adult survival, age at maturity, and the reproductive interval of female seals in this population.

Use of an Inverted Synthetic Control Method to Estimate Effects of Recent Drug Overdose Good Samaritan Laws, Overall and by Black/White Race/Ethnicity.

Overdose Good Samaritan laws (GSLs) aim to reduce mortality by providing limited legal protections when a bystander to a possible drug overdose summons help. Most research into the impact of these laws is dated or potentially confounded by coenacted naloxone access laws. Lack of awareness and trust in GSL protections, as well as fear of police involvement and legal repercussions, remain key deterrents to help-seeking. These barriers may be unequally distributed by race/ethnicity due to racist policing and drug policies, potentially producing racial/ethnic disparities in the effectiveness of GSLs for reducing overdose mortality. We used 2015-2019 vital statistics data to estimate the effect of recent GSLs on overdose mortality, overall (8 states) and by Black/White race/ethnicity (4 states). Given GSLs' near ubiquity, few unexposed states were available for comparison. Therefore, we generated an "inverted" synthetic control method (SCM) to compare overdose mortality in new-GSL states with that in states that had GSLs throughout the analytical period. The estimated relationships between GSLs and overdose mortality, both overall and stratified by Black/White race/ethnicity, were consistent with chance. An absence of effect could result from insufficient protection provided by the laws, insufficient awareness of them, and/or reticence to summon help not addressable by legal protections. The inverted SCM may be useful for evaluating other widespread policies.

When Effects Cannot be Estimated: Redefining Estimands to Understand the Effects of Naloxone Access Laws.

Violations of the positivity assumption (also called the common support condition) challenge health policy research and can result in significant bias, large variance, and invalid inference. We define positivity in the single- and multiple-timepoint (i.e., longitudinal) health policy evaluation setting, and discuss real-world threats to positivity. We show empirical evidence of the practical positivity violations that can result when attempting to estimate the effects of health policies (in this case, Naloxone Access Laws). In such scenarios, an alternative is to estimate the effect of a shift in law enactment (e.g., the effect if enactment had been delayed by some number of years). Such an effect corresponds to what is called a modified treatment policy, and dramatically weakens the required positivity assumption, thereby offering a means to estimate policy effects even in scenarios with serious positivity problems. We apply the approach to define and estimate the longitudinal effects of Naloxone Access Laws on opioid overdose rates.

Genetic management on the brink of extinction: sequencing microsatellites does not improve estimates of inbreeding in wild and captive Vancouver Island marmots (Marmota vancouverensis).

Captive breeding is often a last resort management option in the conservation of endangered species which can in turn lead to increased risk of inbreeding depression and loss of genetic diversity. Thus, recording breeding events via studbook for the purpose of estimating relatedness, and facilitating mating pair selection to minimize inbreeding, is common practice. However, as founder relatedness is often unknown, loss of genetic variation and inbreeding cannot be entirely avoided. Molecular genotyping is slowly being adopted in captive breeding programs, however achieving sufficient resolution can be challenging in small, low diversity, populations. Here, we evaluate the success of the Vancouver Island marmot (Marmota vancouverensis; VIM; among the worlds most endangered mammals) captive breeding program in preventing inbreeding and maintaining genetic diversity. We explored the use of high-throughput amplicon sequencing of microsatellite regions to assay greater genetic variation in both captive and wild populations than traditional length-based fragment analysis. Contrary to other studies, this method did not considerably increase diversity estimates, suggesting: (1) that the technique does not universally improve resolution, and (2) VIM have exceedingly low diversity. Studbook estimates of pairwise relatedness and inbreeding in the current population were weakly, but positively, correlated to molecular estimates. Thus, current studbooks are moderately effective at predicting genetic similarity when founder relatedness is known. Finally, we found that captive and wild populations did not differ in allelic frequencies, and conservation efforts to maintain diversity have been successful with no significant decrease in diversity over the last three generations. Supplementary Information: The online version contains supplementary material available at 10.1007/s10592-022-01429-7.

Spatiotemporal Analysis of the Association Between Pain Management Clinic Laws and Opioid Prescribing and Overdose Deaths.

Pain management clinic (PMC) laws were enacted by 12 states to promote appropriate opioid prescribing, but their impact is inadequately understood. We analyzed county-level opioid overdose deaths (National Vital Statistics System) and patients filling long-duration (≥30 day) or high-dose (≥90 morphine milligram equivalents per day) opioid prescriptions (IQVIA, Inc.) in the United States in 2010-2018. We fitted Besag-York-Mollié spatiotemporal models to estimate annual relative rates (RRs) of overdose and prevalence ratios (PRs) of high-risk prescribing associated with any PMC law and 3 provisions: payment restrictions, site inspections, and criminal penalties. Laws with criminal penalties were significantly associated with reduced PRs of long-duration and high-dose opioid prescriptions (adjusted PR = 0.82, 95% credible interval (CrI): 0.82, 0.82, and adjusted PR = 0.73, 95% CI: 0.73, 0.74 respectively) and reduced RRs of total and natural/semisynthetic opioid overdoses (adjusted RR = 0.86, 95% CrI: 0.80, 0.92, and adjusted RR = 0.84, and 95% CrI: 0.77, 0.92, respectively). Conversely, PMC laws were associated with increased relative rates of synthetic opioid and heroin overdose deaths, especially criminal penalties (adjusted RR = 1.83, 95% CrI: 1.59, 2.11, and adjusted RR = 2.59, 95% CrI: 2.22, 3.02, respectively). Findings suggest that laws with criminal penalties were associated with intended reductions in high-risk opioid prescribing and some opioid overdoses but raise concerns regarding unintended consequences on heroin/synthetic overdoses.

Prescription Opioid Laws and Opioid Dispensing in US Counties: Identifying Salient Law Provisions With Machine Learning.

BACKGROUND: Hundreds of laws aimed at reducing inappropriate prescription opioid dispensing have been implemented in the United States, yet heterogeneity in provisions and their simultaneous implementation have complicated evaluation of impacts. We apply a hypothesis-generating, multistage, machine-learning approach to identify salient law provisions and combinations associated with dispensing rates to test in future research. METHODS: Using 162 prescription opioid law provisions capturing prescription drug monitoring program (PDMP) access, reporting and administration features, pain management clinic provisions, and prescription opioid limits, we used regularization approaches and random forest models to identify laws most predictive of county-level and high-dose dispensing. We stratified analyses by overdose epidemic phases-the prescription opioid phase (2006-2009), heroin phase (2010-2012), and fentanyl phase (2013-2016)-to further explore pattern shifts over time. RESULTS: PDMP patient data access provisions most consistently predicted high-dispensing and high-dose dispensing counties. Pain management clinic-related provisions did not generally predict dispensing measures in the prescription opioid phase but became more discriminant of high dispensing and high-dose dispensing counties over time, especially in the fentanyl period. Predictive performance across models was poor, suggesting prescription opioid laws alone do not strongly predict dispensing. CONCLUSIONS: Our systematic analysis of 162 law provisions identified patient data access and several pain management clinic provisions as predictive of county prescription opioid dispensing patterns. Future research employing other types of study designs is needed to test these provisions' causal relationships with inappropriate dispensing and to examine potential interactions between PDMP access and pain management clinic provisions. See video abstract at, http://links.lww.com/EDE/B861.

Legal Authority for Emergency Medical Services to Increase Access to Buprenorphine Treatment for Opioid Use Disorder.

Treatment with buprenorphine significantly reduces both all-cause and overdose mortality among individuals with opioid use disorder. Offering buprenorphine treatment to individuals who experience a nonfatal opioid overdose represents an opportunity to reduce opioid overdose fatalities. Although some emergency departments (EDs) initiate buprenorphine treatment, many individuals who experience an overdose either refuse transport to the ED or are transported to an ED that does not offer buprenorphine. Emergency medical services (EMS) professionals can help address this treatment gap. In this Concepts article, we describe the federal legal landscape that governs the ability of EMS professionals to administer buprenorphine treatment, and discuss state and local regulatory considerations relevant to this promising and emerging practice.

Regional and temporal effects of naloxone access laws on opioid overdose mortality.

BACKGROUND: Naloxone is a drug that reverses opioid overdose. Naloxone Access Laws (NALs) increase public access to naloxone and have been considered as one promising solution to reducing opioid-related harm. However, previous studies on whether NALs are effective in reducing opioid overdose mortality found somewhat contradictory results. Our study attempts to provide a more definitive answer to this question by utilizing an approach that matches NAL vs non-NAL states and stratifies by US region and years of implementation. Methods: We assess the causal impact of NALs on state-level opioid-related mortality rate by constructing a comparison group using matching to produce a valid counterfactual scenario, and estimating the effects of NAL using a semi-dynamic staggered difference in differences (DID) model that allows heterogeneous effects across regions and years of implementation. State-level opioid-related mortality data from CDC's WONDER database and NALs effective from 1999 to 2014 were utilized. Results: We find that NAL effects have reduced fatal opioid-related overdose in western states and have produced minimal or no effects for other regions. Conclusions: The effects of NALs vary across regions and years of implementation. It is important to study the successful experience of the western states.

Measuring Relationships Between Proactive Reporting State-level Prescription Drug Monitoring Programs and County-level Fatal Prescription Opioid Overdoses.

BACKGROUND: Prescription drug monitoring programs (PDMPs) that collect and distribute information on dispensed controlled substances have been adopted by nearly all US states. We know little about program characteristics that modify PDMP impact on prescription opioid (PO) overdose deaths. METHODS: We measured associations between adoption of any PDMP and changes in fatal PO overdoses in 2002-2016 across 3109 counties in 49 states and D.C. We then measured changes related to the adoption of "proactive PDMPs," which report outlying prescribing/dispensing patterns and provide broader access to PDMP data by law enforcement. Comparisons were made within 3 time intervals that broadly represent the evolution of PDMPs (2002-2004, 2005-2009, and 2010-2016). We modeled overdoses using Bayesian space-time models. RESULTS: Adoption of electronic PDMP access was associated with 9% lower rates of fatal PO overdoses after three years (rate ratio [RR] = 0.91, 95% credible interval [CI]: 0.88-0.93) with well-supported effects for methadone (RR = 0.86,95% CI: 0.82-0.90) and other synthetic opioids (RR = 0.82, 95% CI: 0.77-0.86). Compared with states with no/weak PDMPs, proactive PDMPs were associated with fewer deaths attributed to natural/semi-synthetic opioids (2002-2004: RR = 0.72 [0.66-0.78]; 2005-2009: RR = 0.93 [0.90-0.97]; 2010-2016: 0.89 [0.86-0.92]) and methadone (2002-2004: RR = 0.77 [0.69-0.85]; 2010-2016: RR = 0.90 [0.86-0.94]). Unintended effects were observed for synthetic opioids other than methadone (2005-2009: RR = 1.29 [1.21-1.38]; 2010-2016: RR = 1.22 [1.16-1.29]). CONCLUSIONS: State adoption of PDMPs was associated with fewer PO deaths overall while proactive PDMPs alone were associated with fewer deaths related to natural/semisynthetic opioids and methadone, the specific targets of these programs. See video abstract at, http://links.lww.com/EDE/B619.

Gene flow and climate-associated genetic variation in a vagile habitat specialist.

Previous work in landscape genetics suggests that geographic isolation is of greater importance to genetic divergence than variation in environmental conditions. This is intuitive when configurations of suitable habitat are a dominant factor limiting dispersal and gene flow, but has not been thoroughly examined for habitat specialists with strong dispersal capability. Here, we evaluate the effects of geographic and environmental isolation on genetic divergence for a vagile invertebrate with high habitat specificity and a discrete dispersal life stage: Dod's Old World swallowtail butterfly, Papilio machaon dodi. In Canada, P. m. dodi are generally restricted to eroding habitat along major river valleys where their larval host plant occurs. A series of causal and linear mixed effects models indicate that divergence of genome-wide single nucleotide polymorphisms is best explained by a combination of environmental isolation (variation in summer temperatures) and geographic isolation (Euclidean distance). Interestingly, least-cost path and circuit distances through a resistance surface parameterized as the inverse of habitat suitability were not supported. This suggests that, although habitat associations of many butterflies are specific due to reproductive requirements, habitat suitability and landscape permeability are not equivalent concepts due to considerable adult vagility. We infer that divergent selection related to variation in summer temperatures has produced two genetic clusters within P. m. dodi, differing in voltinism and diapause propensity. Within the next century, temperatures are predicted to rise by amounts greater than the present-day difference between regions of the genetic clusters, potentially affecting the persistence of the northern cluster under continued climate change.