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Inpatient pain management is challenging for clinicians and inequities are prevalent. We examined sex concordance between physicians and patients to determine if discordance was associated with disparate opioid prescribing on hospital discharge. We examined 15,339 hospitalizations from 2013 to 2021. Adjusting for patient, clinical, and hospitalization-level characteristics, we calculated the odds of a patient receiving an opioid on discharge and the days of opioids prescribed across all hospitalizations and for patients admitted with a common pain diagnosis. We did not find an overall association between physician-patient sex concordance and discharge opioid prescriptions. Compared to concordant sex pairs, patients in discordant pairs were not significantly less likely to receive an opioid prescription (odds ratio: 1.04; 95% confidence interval [CI]: 0.95, 1.15) and did not receive significantly fewer days of opioids (2.1 fewer days of opioids; 95% CI: -4.4, 0.4). Better understanding relationships between physician and patient characteristics is essential to achieve more equitable prescribing.

The harmful side effects of opioid drugs such as respiratory depression, tolerance, dependence, and abuse potential have limited the therapeutic utility of opioids for their entire clinical history. However, no previous attempt to develop effective pain drugs that substantially ameliorate these effects has succeeded, and the current opioid epidemic affirms that they are a greater hindrance to the field of pain management than ever. Recent attempts at new opioid development have sought to reduce these side effects by minimizing engagement of the regulatory protein arrestin-3 at the mu-opioid receptor, but there is significant controversy around this approach. Here, we discuss the ongoing effort to develop safer opioids and its relevant historical context. We propose a new model that reconciles results previously assumed to be in direct conflict to explain how different signaling profiles at the mu-opioid receptor contribute to opioid tolerance and dependence. Our goal is for this framework to inform the search for a new generation of lower liability opioid analgesics.

BackgroundAchieving equitable access to medications for opioid use disorder (MOUD) such as buprenorphine is a pressing issue. Evidence suggests disparities in MOUD access based on race and socioeconomic status, further exacerbated by the COVID-19 pandemic. However, the drivers behind this access gap remain poorly understood. This study explores barriers to treatment access among individuals with opioid use disorder (OUD) experiencing homelessness.MethodsWe interviewed 28 individuals in and around the Boston Public Health Commission (BPHC) Engagement Center, an area known for its high density of active substance use and homelessness. We asked about people's experiences, perceptions, and attitudes toward OUD treatment. We conducted a thematic analysis of our interview data.ResultsFifty-four percent of participants sampled were not prescribed MOUD. None of the participants reported having an active prescription of sublingual buprenorphine or buprenorphine/naloxone. White participants were more likely to have been prescribed buprenorphine in the past compared to participants of other races even in this socioeconomically homogeneous sample. Themes that emerged in our data included challenges to accessing MOUD due to reduced services during the COVID-19 pandemic, lost or stolen medications, fewer inpatient withdrawal management beds for women, transportation challenges, fear of adverse effects of MOUD, the perception that taking MOUD replaces one addiction for another, and community disapproval of MOUD. Participants also reported stigma and discrimination based on race, gender, and socioeconomic status.ConclusionSystems and individual-level factors contribute to the MOUD treatment gap across race and socioeconomic status. The COVID-19 pandemic posed additional access challenges. This study provides important, actionable insights about the barriers faced by a particularly vulnerable population of individuals with OUD experiencing homelessness.

Background: Since 2008, several cases of pregabalin abuse have been reported to the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Despite this evidence, gabapentinoids are increasingly being prescribed. Moreover, pregabalin is being used in a recreational setting for its dissociative effects and euphoria. Objectives: To assess the characteristics of non-therapeutic users of pregabalin and to show behavioral trends associated with requests for the medicine at community pharmacies. Methods: The Medicine Abuse Observatory (MAO), an epidemiological surveillance system, was able to analyze trends about the most diverted drugs and the behavioral patterns of the population from community pharmacies. We have conducted an observational and cross-sectional study from January 2022 to April 2023, to determinate trends in the behavior of patients who have requested pregabalin in the Catalan Sephanet. Results: Behavior with respect to sex was similar in all health problems, although one difference was raised when considering neuropathic pain, in which the females were more involved (72.7%), especially around 2.5 times more than the males (27.3%, p < 0.05). The study showed a potential recreational use related to patients aged <25 years and patients aged 25–35 years (p < 0.05). Neuropathic pain was mainly identified in patients >65 years. In 75% of the cases, there was a preceding prescription. Conclusions: This study underlines the evidence of non-therapeutic use of pregabalin among the Catalan population and the need to take control measures. Actions should be promoted, both at the level of prescription and dispensing, and focusing on education and knowledge about the risks that may appear with the use of pregabalin. [ABSTRACT FROM AUTHOR]

Over the past two decades, the escalating prescription of opioid medications for pain management has culminated in a widespread opioid epidemic, significantly impacting public health, social dynamics, and economic stability. The urgent need for improved treatments for opioid addiction necessitates a deeper understanding of its biological underpinnings, with genetic variations playing a crucial role in individual susceptibility to opioid use disorder (OUD) and influencing clinical practices. In this study, we leverage the genetic diversity of four rat strains (ACI/N, BN/NHsd, WKY/N, and F344/N) to examine the contribution of genetic factors to oxycodone metabolism and addiction-like behaviors. We used the extended access to intravenous oxycodone self-administration procedure (12 h/day, 0.15 mg/kg/injection) to comprehensively characterize oxycodone-related behaviors and pharmacokinetics. We measured escalation of oxycodone self-administration, motivation for drug consumption, tolerance to the analgesic effects of oxycodone, withdrawal-induced hyperalgesia, and oxycodone-induced respiratory depression. Additionally, we examined oxycodone-seeking behavior after four weeks of withdrawal by reintroducing the animals to environmental and cue stimuli previously associated with oxycodone self-administration. The findings revealed notable strain differences in several behavioral measures, including oxycodone metabolism. Intriguingly, BN/NHsd and WKY/N strains exhibited similar drug intake and escalation patterns but displayed significant disparities in oxycodone and oxymorphone metabolism. Minimal sex differences were observed within strains, primarily relating to oxycodone metabolism. In conclusion, this study identifies strain differences in the behavioral responses and pharmacokinetics associated with oxycodone self-administration in rats, providing a robust foundation for identifying genetic and molecular variants associated with various facets of the opioid addiction process.

Pregabalin (PGB) has been commonly subjected to diversion, from being a prescription drug to a recreational drug. In this study, pregabalin use (which is one of the substances subject to control in Turkey) and the concomitant use of other substances in cases admitted to the Izmir Forensic Medicine Institute was evaluated. Samples from 15,259 cases were screened, between June 2017 and December 2018, for the presence of PGB, and PGB positive cases were further analyzed. Of all cases screened, PGB was detected in 3.2% (n = 487). The mean age of PGB positive cases was 29.24 ± 10.34 years old (min: 14, max: 84), and 94% of them were male. Cannabis metabolite THC-COOH was the most common substance detected in the blood samples following PGB. Overall, 8 other substances were commonly used along with PGB. These substances were cannabis, morphine, hydromorphone, codeine, hydrocodone, heroin, paracetamol, and naproxen. Finally, we observed similar results in urine analysis. This research provides systematic data for PGB use in forensic cases in Turkey. The study findings indicate that PGB and multiple drug use increased over time, and providers should be particularly careful when prescribing PGB. [ABSTRACT FROM AUTHOR]

BackgroundFentanyl- and methamphetamine-based counterfeit prescription drugs have driven escalating overdose death rates in the US, however their presence in Mexico has not been assessed. Our ethnographic team has conducted longitudinal research focused on illicit drug markets in Northern Mexico since 2018. In 2021-2022, study participants described the arrival of new, unusually potent tablets sold as ostensibly controlled substances, without a prescription, directly from pharmacies that cater to US tourists.AimsTo characterize the availability of counterfeit and authentic controlled substances at pharmacies in Northern Mexico available to English-speaking tourists without a prescription.MethodsWe employed an iterative, exploratory, mixed methods design. Longitudinal ethnographic data was used to characterize tourist-oriented micro-neighborhoods and guide the selection of n=40 pharmacies in n=4 cities in Northern Mexico. In each pharmacy, samples of "oxycodone", "Xanax", and "Adderall" were sought as single pills, during English-language encounters, after which detailed ethnographic accounts were recorded. We employed immunoassay-based testing strips to check each pill for the presence of fentanyls, benzodiazepines, amphetamines, and methamphetamines. We used Fourier-Transform Infrared Spectroscopy to further characterize drug contents.ResultsOf n=40 pharmacies, one or more of the requested controlled substances could be obtained with no prescription (as single pills or in bottles) at 28 (70.0%) and as single pills at 19 (47.5%). Counterfeit pills were obtained at 11 pharmacies (27.5%). Of n=45 samples sold as one-off controlled substances, 18 were counterfeit. 7 of 11 (63.6%) samples sold as "Adderall" contained methamphetamine, 8 of 27 (29.6%) samples sold as "Oxycodone" contained fentanyl, and 3 "Oxycodone" samples contained heroin. Pharmacies providing counterfeit drugs were uniformly located in tourist-serving micro-neighborhoods, and generally featured English-language advertisements for erectile dysfunction medications and "painkillers". Pharmacy employees occasionally expressed concern about overdose risk and provided harm reduction guidance.DiscussionThe availability of fentanyl-, heroin-, and methamphetamine-based counterfeit medications in tourist-oriented independent pharmacies in Northern Mexico represents a public health risk, and occurs in the context of 1) the normalization of medical tourism as a response to rising unaffordability of healthcare in the US, 2) plummeting rates of opioid prescription in the US, affecting both chronic pain patients and the availability of legitimate pharmaceuticals on the unregulated market, 3) the rise of fentanyl-based counterfeit opioids as a key driver of the fourth, and deadliest-to-date, wave of the opioid crisis. It was not possible to distinguish counterfeit medications based on appearance of pills or geography of pharmacies, because identically-appearing authentic and counterfeit versions were often sold in close geographic proximity. Nevertheless, people who consume drugs may be more trusting of controlled substances purchased directly from pharmacies. Due to Mexico's limited opioid overdose surveillance infrastructure, the current death rate from these substances remains unknown.

IntroductionDrug overdoses have reached a historic milestone of over 100,000 deaths in a single year, 75,673 related to opioids. The acceleration in opioid-related deaths coupled with stark health inequities demands a close examination of opioid use disorder (OUD) treatment barriers and swift consideration of policy changes.DesignThe aim of this buprenorphine policy analysis is to summarize existing buprenorphine barriers and present policy solutions to improve access and actualize the contributions of Advanced Practice Registered Nurses (APRNs).MethodsThe policy analysis follows five sequential steps: (1) defining the problem, (2) identifying key stakeholders, (3) assessing the landscape of relevant policies, (4) describing viable policy options, and (5) making final recommendations.ResultsAlthough there are laudable efforts to improve buprenorphine access, such as the new buprenorphine guidelines issued in April 2021, without larger-scale changes to federal, state, and scope of practice laws, overdose rates will continue to rise. We recommend a multipronged policy approach to improve buprenorphine treatment access, including eliminating the DEA X waiver, improving OUD education, and adopting full practice authority for APRNs in all states.ConclusionIncremental change is no longer sufficient to address opioid overdose deaths. Bolder and coordinated policy action is possible and necessary to empower the full clinical workforce to apply evidence-based life-saving treatments for OUD. The critical contributions of nurses in advancing equitable access to OUD care are emphasized in the National Academy of Medicine's Report, Future of Nursing: Charting a Path to Achieve Health Equity. Nurses are named as instrumental in improving buprenorphine access. Policy changes that acknowledge and build on evidence-based treatment expansion strategies are sorely needed.Clinical relevanceOne of the most robust tools to combat opioid overdose deaths is buprenorphine, a partial opioid agonist, and gold standard medication treatment for OUD, but only 5% of the prescribing workforce possess the required Drug Enforcement Agency (DEA) X waiver. A growing body of evidence demonstrates that Advanced Practice Registered Nurses are accelerating the growth in waiver update and buprenorphine use, despite the considerable barriers and limitations described in this policy analysis.

BackgroundOpioid misuse is a major public health concern in the United States. Opioid agonist medications are evidence-based treatments for opioid use disorders (OUD) that can be prescribed by advance practice registered nurses (APRNs) with prescriptive authority and appropriate training.PurposeArticle examines factors influencing preparation to provide medications for opioid use disorder (MOUD) in APRN education.MethodsData from semi-structured interviews addressing the role of education in preparing APRNs to provide MOUD were grouped into key themes using thematic analysis. Data were collected in a mixed methods study in four states with high opioid overdose deaths whose main findings were previously published.FindingsTwo overarching themes emerged: "addressing attitudes" and "curriculum change." Sub-themes include affective barriers to providing OUD treatment; motivation to respond to the OUD crisis; and attitude change through experience with MOUD.Discussion and conclusionAPRNs can play a key role in reducing the harms caused by OUD. Attention to attitudinal issues, such as stigma, toward people using opioids is important in educating APRNs about providing MOUD.

IntroductionIn March 2016, the Centers for Disease Control and Prevention released the Guideline for Prescribing Opioids for Chronic Pain, intended for primary care clinicians. One recommendation advised against concurrent prescription of opioids and benzodiazepines. Although existing research suggests a reduction in co-prescribing of these drug classes by clinicians after guideline release, there are limited data assessing its possible effect on patient medical outcomes, such as overdoses.MethodsThis retrospective observational study analyzed opioid and benzodiazepine exposures, alone or in combination, reported to the California Poison Control System from January 2012 to June 2021. Interrupted time series analyses identified the difference in monthly call volume between pre- and post-guideline release. For exposures resulting in serious medical outcomes, additional analyses assessed trends and identified associated variables.ResultsThere was no significant change in concomitant opioid and benzodiazepine exposures reported to California Poison Control System between pre- and post-guideline release. Compared to pre-guideline release, exposures to a single opioid or to a single benzodiazepine significantly decreased by 1.07 (95% CI: -1.62, -0.51) and 1.82 (95% CI: -2.33, -1.31) calls per month, respectively, after the guideline release. For exposure calls associated with serious medical outcomes, there was a significant increase of 0.11 (95% CI: 0.04, 0.18) and 0.2 (95% CI: 0.05, 0.34) calls per month for concomitant opioid and benzodiazepine and single opioid exposures, respectively, following guideline release.DiscussionThe guideline release appeared to have a variable association with exposures to single opioid, single benzodiazepines, and concomitant opioid and benzodiazepine cases reported to California Poison Control System. Although exposures to opioids or benzodiazepines alone significantly decreased after guideline release, there was no significant change in concomitant exposures. Additionally, for exposures associated with serious medical outcomes, concomitant exposures, and single opioid exposures significantly increased following guideline release.ConclusionOur results suggest that the guideline was not associated with a corresponding decrease in the number of concomitant poisoning exposures reported to California Poison Control System. Additional interventions may be needed to reduce concomitant exposures to opioids and benzodiazepines.

ObjectiveTo describe the evolution of perioperative opioid management in gynecologic oncology patients after open surgeries and determine current opioid over-prescription rates.MethodsPart one of this two-part study was a retrospective chart review of adult patients who underwent laparotomy by a gynecologic oncologist from July 1, 2012 to June 30, 2021, comparing changes in clinical characteristics, pain management and discharge opioid prescription sizes between fiscal year 2012 (FY2012) and 2020 (FY2020). In part two, we prospectively surveyed patients after laparotomy in 2021 to determine opioid use after hospital discharge.Results1187 patients were included in the chart review. Demographic and surgical characteristics remained stable from FY2012 to FY2020 with differences notable for increased rates of interval cytoreductive surgeries for advanced ovarian cancer and decreased rates of full lymph node dissection. Median inpatient opioid use decreased by 62 % from FY2012 to FY2020. Median discharge opioid prescription size was 675 oral morphine equivalents (OME) per patient in FY2012 and decreased by 77.7 % to 150 OME in FY2020. Of 95 surveyed patients in 2021, median self-reported opioid use after discharge was 22.5 OME. Patients had an excess of opioids equivalent to 1331 doses of 5-milligram oxycodone tablets per 100 patients.ConclusionInpatient opioid use in our gynecologic oncology open surgical patients and post-discharge opioid prescription size significantly decreased over the last decade. Despite this progress, our current prescribing patterns continue to significantly overestimate patients' actual opioid use after hospital discharge. Individualized point of care tools are needed to determine an appropriate opioid prescription size.

BackgroundBuprenorphine is an effective treatment for opioid use disorders. A previous randomized trial comparing emergency department (ED)-initiated buprenorphine to standard care showed dramatic improvement in follow-up. This is encouraging, but must be replicated to understand the generalizability of buprenorphine treatment.ObjectivesEvaluate the efficacy of an ED-initiated buprenorphine protocol similar to a previous randomized trial in a different population.MethodsThis ED-based descriptive study described the results of a project implementing an opioid use disorder treatment protocol that included buprenorphine. Patients with opioid use disorder were offered treatment with buprenorphine, a buprenorphine prescription whenever possible, and a follow-up visit to a clinic providing addiction treatment. The primary outcome was engagement in formal addiction treatment 30 days after the index visit.ResultsOf the 210 patients who accepted referral for outpatient medication-assisted treatment, 95 (45.2%) achieved the primary outcome. Two-thirds of these patients received a buprenorphine prescription at discharge; 40% were homeless. A regression analysis revealed one statistically significant predictor of the primary outcome: patients who were housed were 2.49 times more likely to engage in opioid use disorder treatment than patients who were homeless (p = 0.02).ConclusionsIn this descriptive study of an ED-initiated buprenorphine protocol, follow-up was less than that reported in a previous randomized controlled trial. Two important differences between our study and the randomized trial are the high rate of homelessness and the fact that not every patient received a prescription for buprenorphine. The efficacy of ED-initiated treatment may depend on certain population characteristics.

Over 50,000 people die annually from opioid overdoses in the United States leading to what has become known as the “opioid epidemic.” This is of heightened concern in states like Alabama that experience higher rates of overall drug use and overdose deaths. Thus, it is increasingly important for college students in Alabama to learn about how the opioid epidemic is affecting their communities. Previous studies have demonstrated that engaging non-majors in innovative active-learning oriented pedagogies like service-learning can enhance their understanding and awareness about contemporary societal issues. Despite its pedagogical potential, the impact of opioid-related service-learning, particularly for non-majors, continues to remain unexplored. In this study, we describe the implementation of a service-learning module centered on opioid addiction. Students in a non-major biology course learned the science behind opioids, had Naloxone training, and engaged in active discussions with an opioid researcher, physician, and former illicit opioid user. Our assessment of the thematic analysis of pre- and post-reflection free-write data from 87 consenting students revealed 10 categories that students reported in the post- but not pre-reflections (essay gain), pre- and post-reflections (neutral), and pre- but not post-reflections (essay loss). We found essay gains in students humanizing addiction and awareness of the cultural context of opioid addiction and essay losses from students indicating that non-major students had a low level of awareness related to these issues. Eight one-on-one, semi-structured interviews revealed that students were personally impacted by the epidemic and valued its curricular inclusion. Our data supports that service-learning can increase non-major biology student’s awareness and contextual understanding about the opioid epidemic, enabling much-needed advocacy to further enhance its awareness among the public.

Grim national statistics about the U.S. opioid crisis are increasingly well known to the American public. Far less well known is that U.S. servicemembers are at ground zero of the epidemic, with veterans facing an overdose death rate of up to twice that of civilians. Exploiting a quasi-experiment in overseas deployment assignment, this study estimates the causal impact of combat exposure among the deployed in the Global War on Terrorism on opioid abuse. We find that exposure to war theater substantially increased the risk of prescription painkiller abuse and illicit heroin use among active duty servicemen. The magnitudes of our estimates imply lower-bound combat exposure-induced healthcare costs of $1.04 billion per year for prescription painkiller abuse and $470 million per year for heroin use. [ABSTRACT FROM AUTHOR]

BackgroundChronic pain affects one-fifth of US adults. Reductions in opioid prescribing have been associated with increased non-prescription opioid use and, chronologically, increased stimulant (methamphetamine and cocaine) use. While non-prescription opioid use is commonly attributed to pain self-management, the role of stimulants in managing pain is unclear.MethodsWe analyzed baseline data from a longitudinal study of patients with chronic non-cancer pain in an urban safety-net healthcare system who had been prescribed an opioid for ≥3 of the last 12 months, and had a history of non-prescription opioid, cocaine, or amphetamine use (N = 300). We estimated the prevalence and identified correlates of stimulant use to treat pain among a subgroup of patients who reported past-year stimulant use (N = 105). Data sources included computer-assisted questionnaire (demographics, substance use, pain), clinical exam and procedures (pain, pain tolerance), and chart abstraction (opioid prescriptions). We conducted bivariate analyses to assess associations between demographics, pain characteristics, non-opioid therapies, substance use, opioid prescriptions, and self-reported symptoms, with reporting using stimulants to treat pain. Demographic variables and those with significant bivariate associations were included in a multivariable logistic regression model.ResultsFifty-two percent of participants with past-year stimulant use reported using stimulants in the past year to treat pain. Participants who used stimulants for pain reported slightly higher average pain in the past 3 months (median of 8 (IQR: 6-8) vs 7 (7-9) out of 10, p = 0.049). In the multivariable analysis, female gender (AOR= 3.20, 95% CI: 1.06-9.63, p = 0.039) and higher score on the Douleur Neuropathique 4 neuropathic pain questionnaire (AOR = 1.34, 95% CI: 1.05-1.70, p = 0.017) were associated with past-year stimulant use to treat pain.ConclusionStimulants may be used for pain self-management, particularly for neuropathic pain and among women. Our findings suggest an underexplored motivation for stimulant use in an era of reduced access to prescribed opioids.

Prescription opioids are a primary driver of opioid-related deaths. Although craving is a substantial component of OUD, the degree to which craving leads to misuse among chronic pain patients on long-term prescription opioids is unknown. A clear understanding of the factors that lead to misuse in this vulnerable population is needed for the development of safe and effective practices for opioid taper. This narrative review summarizes the relevant literature on the role of craving in addiction and chronic pain through epidemiological and behavioral studies. The first part of this review examines the role of craving in predicting opioid use/misuse in individuals with chronic pain with and without OUD. The second part covers methods on how craving is evaluated experimentally using both subjective and objective measures and provides related findings. The overall goal of this review is to facilitate the development of a population-specific description of craving in those who use opioids to control chronic pain and to describe how it may be mechanistically linked to patterns of opioid (mis)use.

AbstractThe United States faces a crisis because of the high prevalence of chronic pain, concurrent opioid use disorder, and overdose deaths. Prescription opioids remain a primary driver of opioid-related deaths. Craving is a core symptom of addiction, yet the degree to which craving plays a role in prescription opioid use among patients with chronic pain is unknown. Understanding the degree to which craving should be considered in patients with chronic pain is critical for developing effective interventions for supporting patients through opioid tapering. The current work combines data collected from (1) 2152 veterans screened for eligibility at a pain specialty care clinic at the San Francisco VA Health Care System and (2) medical records obtained from the VA Corporate Data Warehouse. We found that prescription opioid craving among veterans with chronic pain was low, with 66.4% of the sample reporting no craving and 33.6% reporting craving. We also found that craving had a small association with morphine equivalent daily dose and pain severity but was more strongly associated with depression. Craving of prescription opioids among veterans with chronic pain is complex. Findings are discussed in relation to chronic pain symptoms, psychiatric comorbidities, and demographics.

Background: Deaths due to opioid overdose continue to rise in the United States. Despite availability of effective treatment for opioid use disorder, uptake is low among those who misuse opioids. Methods: This paper explores the role of misconception, stigma, and misinformation in influencing decisions to initiate medications for opioid use disorder among patients and providers. Conclusion: Misinformation about opioids has been prevalent among future healthcare providers and first responders as well as pharmaceutical companies, which may have implications for treatment. Among individuals with opioid use disorder, treatment uptake and adherence have been negatively affected by misconceptions about treatment efficacy and side effects, as well as stigma. We discuss the role of social media, education, and the community, in mitigating misinformation and addressing misconceptions about opioids and treatment options.

AbstractThere are reports of AA amyloidosis associated with intravenous and/or subcutaneous injection of street drugs, such as heroin and cocaine. Most reports describe patients with substance use disorder, renal amyloidosis and concurrent viral infections, such as hepatitis and/or human immunodeficiency virus. Herein, we present a case of systemic AA amyloidosis and sepsis in a 34-year-old woman with a history of intravenous injection of oral prescription medications (as evidenced by excipient lung disease) who had no known history of human immunodeficiency virus nor of hepatitis B or C. Our case shows the broader spectrum of pathology that can occur with the misuse of prescription medications.

IntroductionOutpatient opioid prescribing is associated with opioid misuse in young adults, but the longitudinal association between general healthcare exposure and opioid misuse has not been explored. The objective of this study is to examine the association between healthcare exposure in young adulthood and future opioid misuse.MethodsData were drawn from the National Longitudinal Study of Adolescent to Adult Health (2001-2018) and analyzed in 2021. Healthcare exposure (i.e., inpatient hospitalization and visits to the clinic, emergency department, mental-health facility, or dentist) between individuals aged 18 and 26 years was the primary independent variable; only patients who did not report opioid misuse at baseline were included. Opioid misuse was defined as using prescription painkillers without a doctor's permission and was measured 17 years after exposure. Multivariable logistic regression was used to examine any associations with opioid misuse (ages 33-43 years).ResultsA total of 8,225 young adults with a mean baseline age of 21.8 (SE=0.12) years met inclusion criteria. Approximately 13.7% reported new opioid misuse at follow-up. Those reporting opioid misuse at follow-up were more likely to be White, lack a college education, or report depression. Those exposed to inpatient hospitalization, emergency departments, or mental-health facilities had an increased risk of future opioid misuse.ConclusionsIn young adults reporting no opioid misuse at baseline, healthcare exposure was associated with an increased risk of opioid misuse later in adulthood in this large, national cohort. Physicians encounter this at-risk population daily, reinforcing the importance of responsible prescribing practices and the need for targeted screening, patient education, and intervention efforts in the healthcare setting.

BackgroundThe Centers for Disease Control and Prevention's (CDC) March 2016 opioid prescribing guideline did not include prescribing recommendations for surgical pain. Although opioid over-prescription for surgical patients has been well-documented, the potential effects of the CDC guideline on providers' opioid prescribing practices for surgical patients in the United States remains unclear.MethodsWe conducted an interrupted time series analysis (ITSA) of 37,009 opioid-naïve adult patients undergoing inpatient surgery from 2013-2019 at an academic medical center. We assessed quarterly changes in the discharge opioid prescription days' supply, daily and total doses in oral morphine milligram equivalents (OME), and the proportion of patients requiring opioid refills within 30 days of discharge.ResultsThe discharge opioid prescription declined by -0.021 (95% CI, -0.045 to 0.003) days per quarter pre-guideline versus -0.201 (95% CI, -0.223 to -0.179) days per quarter post-guideline (p

ObjectivesTo measure the rate of benzodiazepine receptor agonist (BZA) dependence in older veterans with insomnia symptoms chronically using BZAs and to assess for associations between high posttraumatic stress disorder (PTSD) risk and BZA dependence.MethodsA cross-sectional study was conducted among veterans aged 55 years and older with insomnia symptoms (current or historical) and chronic use of BZAs (≥3 months). Measurements included the Primary Care-PTSD screen (score >2 indicates high PTSD risk) and Benzodiazepine Dependence Questionnaire. Logistic regression was used to test for associations between PTSD risk and BZA dependence.ResultsA high PTSD risk was observed in 40% of the participants (N = 33). One-fifth (21.7%, N = 18) of participants met the criteria for benzodiazepine dependence (score ≥23 on Benzodiazepine Dependence Questionnaire). Veterans with high PTSD risk were significantly more likely to have BZA dependence (odds ratio 10.09, 95% CI [2.39, 42.54], p = .002).ConclusionsIn older veterans with insomnia symptoms and chronic use of BZAs, high PTSD risk is associated with elevated risk for BZA dependence, which may make discontinuation of these medications difficult.Clinical implicationsClinicians should consider the strong association between PTSD symptoms and benzodiazepine dependence when developing plans to taper a BZA in veterans with these symptoms.

ObjectivesTo evaluate how performing artists (PAs) with chronic pain may differ on measures of substance use compared to non-PA controls.Methods157 participants reporting chronic pain (89 PAs, 68 non-PA controls) completed an online cross-sectional survey. Participants were assessed for self-reported current pain severity using the Brief Pain Inventory Short-Form, opioid misuse risk using the Screener and Opioid Assessment for Patients with Pain-Revised, opioid withdrawal using the Subjective Opiate Withdrawal Scale, and symptoms of opioid use disorder (OUD) using a modified version of the DSM-V checklist.ResultsPAs had lower pain severity (p

Study designRetrospective case series.ObjectivesTo evaluate the variability in opioid prescription following primary single-level lumbar microdiscectomy.MethodsWe retrospectively reviewed consecutive patients who underwent primary single-level lumbar microdiscectomy. Only opioid-naïve patients ≥18 years old were included. Patients who had revision microdiscectomy, multilevel decompression, and/or any complication requiring prolonged hospital stay (>2 days) were excluded. The primary outcomes were the maximum daily dosage of opioids prescribed in morphine milligram equivalents (MME) and the number of pills prescribed (equivalent to 5 mg hydrocodone).ResultsBetween 2014 and 2019, 169 patients (90 men, 79 women) met inclusion criteria, with a mean age of 46.9 years. Surgery resulted in a statistically significant improvement in VAS (Visual Analogue Scale) score (6.4 to 2.5, P < .01). At discharge, 8 patients (4.7%) did not receive any opioid prescription. Of the remaining 161 patients, 1 patient (0.01%) received hydromorphone, 30 (18.6%) Percocet, 43 (26.7%) oxycodone, and 87 Norco (54.0%). The length of opioid prescription was 6.7 days. The maximum daily dosage of opioids prescribed was 70.4 MME (SD 32.1). The total number of pills prescribed was 89.4 (SD 54.7). Twenty-five patients (15.5%) received a refill prescription. Multivariate analysis demonstrated the operating service, prescriber, and hospital admission were statistically significant predictors of maximum daily MME. The prescriber and hospital admission were statistically significant predictors of total number of pills prescribed.ConclusionsWe found significant variability in opioid prescription following primary single-level lumbar microdiscectomy. For standard spinal procedures like lumbar microdiscectomy, opioid-prescribing guidelines should be established to standardize postoperative pain management.

We previously found that human heroin addicts and mice chronically exposed to morphine exhibit a significant increase in the number of detected hypocretin/orexin (Hcrt)-producing neurons. However, it remains unknown how this increase affects target areas of the hypocretin system involved in opioid withdrawal, including norepinephrine containing structures locus coeruleus (LC) and A1/A2 medullary regions. Using a combination of immunohistochemical, biochemical, imaging, and behavioral techniques, we now show that the increase in detected hypocretin cell number translates into a significant increase in hypocretin innervation and tyrosine hydroxylase (TH) levels in the LC without affecting norepinephrine-containing neuronal cell number. We show that the increase in TH is completely dependent on Hcrt innervation. The A1/A2 regions were unaffected by morphine treatment. Manipulation of the Hcrt system may affect opioid addiction and withdrawal.SIGNIFICANCE STATEMENT Previously, we have shown that the hypothalamic hypocretin system undergoes profound anatomic changes in human heroin addicts and in mice exposed to morphine, suggesting a role of this system in the development of addictive behaviors. The locus coeruleus plays a key role in opioid addiction. Here we report that the hypothalamic hypocretin innervation of the locus coeruleus increases dramatically with morphine administration to mice. This increase is correlated with a massive increase in tyrosine hydroxylase expression in locus coeruleus. Elimination of hypocretin neurons prevents the tyrosine hydroxylase increase in locus coeruleus and dampens the somatic and affective components of opioid withdrawal.

PurposeFatal suicides involving opioids are increasingly common, particularly in rural areas. As co-use of opioids with other substances contributes significantly to mortality risk, we examined whether positive screens for opioids with other substances is more prevalent among rural versus urban suicide deaths, as this could have implications for public health strategies to reduce overdose suicides.MethodsData from all states reporting opioid-related overdose suicides in the National Violent Death Reporting System from 2012 to 2015 were used. Relative risk ratios were obtained using multinomial logistic regression, comparing opioid-only to (1) opioid and alcohol, (2) opioid and benzodiazepines, and (3) opioid, alcohol, and benzodiazepines suicides across rurality. Models were fit using robust standard errors and fixed effects for year of death, adjusting for individual, county, and state-level covariates.FindingsThere were 3,781 opioid-overdose suicide decedents (42% female) tested for all 3 substances during the study period. Unadjusted prevalence of positive screens in decedents varied across rurality (P = .022). Urban decedents were more likely to test positive for opioids alone, while rural decedents were more to likely test positive for opioids and benzodiazepines.ConclusionsRural suicides are associated with increased opioid and benzodiazepine positive screens. These findings suggest the need for rural-focused interventions to support appropriate co-prescribing, better health education for providers about risks associated with drug mixing, and more linkages with mental health services.

Substance use disorder is associated with accelerated disease progression in people with human immunodeficiency virus (HIV; PWH). Problem opioid use, including high-dose opioid therapy, prescription drug misuse, and opioid abuse, is high and increasing in the PWH population. Oxycodone is a broadly prescribed opioid in both the general population and PWH. Here, we allowed HIV transgenic (Tg) rats and wildtype (WT) littermates to intravenously self-administer oxycodone under short-access (ShA) conditions, which led to moderate, stable, "recreational"-like levels of drug intake, or under long-access (LgA) conditions, which led to escalated (dependent) drug intake. HIV Tg rats with histories of oxycodone self-administration under LgA conditions exhibited significant impairment in memory performance in the novel object recognition (NOR) paradigm. RNA-sequencing expression profiling of the medial prefrontal cortex (mPFC) in HIV Tg rats that self-administered oxycodone under ShA conditions exhibited greater transcriptional evidence of inflammation than WT rats that self-administered oxycodone under the same conditions. HIV Tg rats that self-administered oxycodone under LgA conditions exhibited transcriptional evidence of an increase in neuronal injury and neurodegeneration compared with WT rats under the same conditions. Gene expression analysis indicated that glucocorticoid-dependent adaptations contributed to the gene expression effects of oxycodone self-administration. Overall, the present results indicate that a history of opioid intake promotes neuroinflammation and glucocorticoid dysregulation, and excessive opioid intake is associated with neurotoxicity and cognitive impairment in HIV Tg rats.

BackgroundIn response to the opioid crisis, over the last 10 years substantial strides have been made to increase the availability of evidence-based treatments for opioid use disorder, in particular buprenorphine maintenance, in the United States. Despite these worthwhile efforts, uptake rates of evidence-based treatment remain relatively low. As part of a broader study of opioid misuse, we examined proximity to evidence-based treatment as a potential barrier to treatment access.MethodsIn 2017-2018, we surveyed 218 individuals misusing prescription opioids or using street opioids in three Southern Californian counties. The study calculated driving distance from place of residence to the closest treatment provider offering buprenorphine or methadone treatment for opioid use disorders.ResultsMedian distance to providers was 3.8 km (2.4 miles). Seventy one (33%) participants had received some form of treatment in the last 3 months; however, only 26 (40%) of these had received buprenorphine or methadone maintenance treatment. Participants receiving treatment at the time of their interview were traveling an average 16.8 km (10.4 miles) to reach treatment, indicating that as a group this population was both willing and able to seek and engage with treatment.ConclusionsIn the suburban and exurban communities in which our study was based, our findings suggest that simple physical proximity to providers of evidence-based treatment for opioid use disorder is no longer a critical barrier. Other barriers to uptake of buprenorphine or methadone maintenance treatment clearly remain and need to be addressed.DisclaimerFindings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

ObjectivesThere has been increased focus nationally on limiting opioid prescriptions. National data demonstrates a decrease in annual opioid prescriptions among emergency medicine physicians. We analyzed data from 2012 to 2020 from a large academic health system in California to understand trends in opioid prescribing patterns for emergency department (ED) discharged patients and assessed the potential impact of two initiatives at limiting local opioid prescriptions.MethodsIn 2012-2020, monthly ED visit data was used to evaluate the total number of outpatient opioid prescriptions and percent of ED visits with opioid prescriptions (as primary outcomes). Descriptive statistics, graphic representation, and segmented regression with interrupted times series were used based on two prespecified time points associated with intensive local initiatives directed at limiting opioid prescribing1) comprehensive emergency medicine resident education and 2) electronic health record (EHR)-based intervention.ResultsBetween March 2012 and July 2020, a total of 41,491 ED discharged patients received an opioid prescription. The three most commonly prescribed drugs were hydrocodone (84.1%), oxycodone (10.8%), and codeine (2.8%). After implementing comprehensive emergency medicine resident education, the total number of opioid prescriptions, the percentage of opioid prescriptions over total ED visit numbers and the total tablet number showed decreasing trends (p's ≤ 0.01), in addition to the natural (pre-intervention) decreasing trends. In contrast, later interventions in the EHR tended to show attenuated decreasing trends.ConclusionsFrom 2012 to 2020, we found that total opioid prescriptions decreased significantly for discharged ED patients. This trend is seen nationally. However, our specific interventions further heightened this downward trend. Evidence-based legislation, policy changes, and educational initiatives that impact prescribing practices should guide future efforts.

ObjectiveCoprescription of opioids and benzodiazepines (BDZ) is associated with adverse outcomes, including greater healthcare utilization and overdose risk. This study aims to examine opioid and BDZ coprescription, dosing, and mortality among patients with and without opioid use disorder (OUD) in a large healthcare system.MethodsUsing data from the California state Prescription Drug Monitoring Program during 2010 to 2014 linked with a large healthcare system electronic health record database and mortality records from the Centers for Disease Control National Death Index, this study examined 5202 patients (1978 with OUD, 3224 controls). Multiple logistic regression analyses were conducted to examine relationships between most recent BDZ and opioid prescription, and their interaction with respect to mortality.ResultsAbout 10.5% of the sample died on or before December 31, 2014. About 17.7% were prescribed BDZ during the final month of observation. Individuals with OUD were prescribed higher average BDZ and opioid doses than those without OUD. After adjusting for covariates, increased prescribed doses of BDZ (odds ratio [OR]=1.34, 95%CI: 1.15-1.55 per 10 mg/d increment) and opioids (OR = 1.04, 95%CI: 1.02-1.05 per 10 mg/d increment) were positively associated with mortality. Non-OUD patients who received both BDZ and opioid prescriptions had a higher mortality than those who received only BDZ or opioids (The ratio of odds ratio (ROR) = 3.83, 95%CI: 1.78-8.21).ConclusionsStudy findings highlight significant mortality associated with the coprescription of opioids and BDZ in a general healthcare setting. Further research is needed to elucidate factors associated with mortality among non-OUD patients who are co-prescribed opioids and BDZ.

Background: Prior to the COVID-19 pandemic, the United States (US) was already facing an epidemic of opioid overdose deaths. Overdose deaths continued to surge during the pandemic. To limit COVID-19 spread and to avoid disruptions in access to medications for opioid use disorder (MOUD), including buprenorphine and methadone, US federal and state agencies granted unprecedented exemptions to existing MOUD guidelines for Opioid Treatment Programs (OTPs), including loosening criteria for unsupervised take-home doses. We conducted a qualitative study to evaluate the impact of these policy changes on MOUD treatment experiences for providers and patients at an OTP in California. Methods: We interviewed 10 providers (including two physicians, five social worker associates, and three nurse practitioners) and 20 patients receiving MOUD. We transcribed, coded, and analyzed all interviews to identify emergent themes. Results: Patient participants were middle-aged (median age 51 years) and were predominantly men (53%). Providers discussed clinical decision-making processes and experiences providing take-homes. Implementation of expanded take-home policies was cautious. Providers reported making individualized decisions, using patient factors to decide if benefits outweighed risks of overdose and misuse. Decision-making factors included patient drug use, overdose risk, housing status, and vulnerability to COVID-19. New patient groups started receiving take-homes and providers noted few adverse events. Patients who received take-homes reported increased autonomy and treatment flexibility, which in turn increased likelihood of treatment stabilization and engagement. Patients who remained ineligible for take-homes, usually due to ongoing non-prescribed opioid or benzodiazepine use, desired greater transparency and shared decision-making. Conclusion: Federal exemptions in response to COVID-19 led to the unprecedented expansion of access to MOUD take-homes within OTPs. Providers and patients perceived benefits to expanding access to take-homes and experienced few adverse outcomes, suggesting expanded take-home policies should remain post-COVID-19. Future studies should explore whether these findings are generalizable to other OTPs and assess larger samples to quantify patient-level outcomes resulting from expanded take-home policies.

IntroductionThe opioid epidemic persists in the United States. The use of opioid medications is often assessed by claims data but potentially underestimated.ObjectivesWe evaluated the temporal trend in the use of opioid and nonopioid pain medications from a national survey.MethodsUsing data from the 2001 to 2018 National Health and Nutrition Examination Survey (NHANES), we examined the current use of prescription analgesics in the past 30 days among 50,201 respondents aged 20 years or older. Joinpoint regressions were used to test statistically meaningful trends of opioid vs nonopioid analgesics.ResultsThe mean percentage of people who had pain medications in the past 30 days was 6.4% (5.3%-7.1%) for opioid and 11.3% (9.0%-14.8%) for nonopioid analgesics. The availability of opioid and nonopioid prescriptions at home has remained stable, except for the slight decline of opioids among cancer-free patients in 2005 to 2018. The most frequently used opioid analgesic medications included hydrocodone/acetaminophen, tramadol, and hydrocodone.ConclusionWe uniquely measured the proportion of people who had opioid and nonopioid pain medications at home in the United States and supplemented the previous knowledge of prescription rates mainly obtained from claims data.

BackgroundGiven the risks of opioids, clinicians are under growing pressure to treat pain with non-opioid medications. Yet non-opioid analgesics such as non-steroidal anti-inflammatory drugs (NSAIDs) have their own risks: patients with kidney disease or gastrointestinal diseases can experience serious adverse events. We examined the likelihood that patients with back pain diagnoses and contraindications to NSAIDs and opioids received an opioid prescription in primary care.MethodsWe identified office visits for back pain from 2012 to 2017 and sampled the first office visit per patient per year (N = 24,543 visits). We created indicators reflecting contraindications for NSAIDs (kidney, liver, cardiovascular/cerebrovascular, and gastrointestinal diseases; concurrent or chronic use of anticoagulants/antiplatelets, chronic corticosteroid use) and opioids (depression, anxiety, substance use (SUD) and bipolar disorders, and concurrent benzodiazepines) and estimated four logistic regression models, with the one model including all patient visits and models 2-4 stratifying for previous opioid use. We estimated the population attributable risk for each contraindication.ResultsIn our model with all patients-visits, patients received an opioid prescription at 4% of visits. The predicted probability (PP) of receiving an opioid was 4% without kidney disease vs. 7% with kidney disease; marginal effect (ME): 3%; 95%CI: 1-4%). For chronic or concurrent anticoagulant/antiplatelet prescriptions, the PPs were 4% vs. 6% (ME: 2%; 95%CI: 1-3%). For concurrent benzodiazepines, the PPs were 4% vs. 11% (ME: 7%, 95%CI: 5-9%) and for SUD, the PPs were 4% vs. 5% (ME: 1%, 95%CI: 0-3%). For the model including patients with previous long-term opioid use, the PPs for concurrent benzodiazepines were 25% vs. 24% (ME: -1%; 95%CI: - 18-16%). The population attributable risk (PAR) for NSAID and opioid contraindications was small. For kidney disease, the PAR was 0.16% (95%CI: 0.08-0.23%), 0.44% (95%CI: 0.30-0.58%) for anticoagulants and antiplatelets, 0.13% for substance use (95%CI: 0.03-0.22%) and 0.20% for concurrent benzodiazepine use (95%CI: 0.13-0.26%).ConclusionsPatients with diagnoses of kidney disease and concurrent use of anticoagulants/antiplatelet medications had a higher probability of receiving an opioid prescription at a primary care visit for low back pain, but these conditions do not explain a large proportion of the opioid prescriptions.

BackgroundLimiting the incidence of opioid-naïve patients who transition to long-term opioid use (i.e., continual use for > 90 days) is a key strategy for reducing opioid-related harms.ObjectiveTo identify variables constructed from data routinely collected by prescription drug monitoring programs that are associated with opioid-naïve patients' likelihood of transitioning to long-term use after an initial opioid prescription.DesignStatewide cohort study using prescription drug monitoring program data PARTICIPANTS: All opioid-naïve patients in California (no opioid prescriptions within the prior 2 years) age ≥ 12 years prescribed an initial oral opioid analgesic from 2010 to 2017.Methods and main measuresMultiple logistic regression models using variables constructed from prescription drug monitoring program data through the day of each patient's initial opioid prescription, and, alternatively, data available up to 30 and 60 days after the initial prescription were constructed to identify probability of transition to long-term use. Model fit was determined by the area under the receiver operating characteristic curve (C-statistic).Key resultsAmong 30,569,125 episodes of patients receiving new opioid prescriptions, 1,809,750 (5.9%) resulted in long-term use. Variables with the highest adjusted odds ratios included concurrent benzodiazepine use, ≥ 2 unique prescribers, and receipt of non-pill, non-liquid formulations. C-statistics for the day 0, day 30, and day 60 models were 0.81, 0.88, and 0.94, respectively. Models assessing opioid dose using the number of pills prescribed had greater discriminative capacity than those using milligram morphine equivalents.ConclusionsData routinely collected by prescription drug monitoring programs can be used to identify patients who are likely to develop long-term use. Guidelines for new opioid prescriptions based on pill counts may be simpler and more clinically useful than guidelines based on days' supply or milligram morphine equivalents.

BackgroundSevere acute pain is still commonly treated with opioid analgesics in the United States, but this practice could prolong the duration of pain.ObjectivesEstimate the risk of experiencing persistent pain after opioid analgesic use after emergency department (ED) discharge among patients with suspected urolithiasis.MethodsWe analyzed data collected for a longitudinal, multicenter clinical trial of ED patients with suspected urolithiasis. We constructed multilevel models to estimate the odds ratios (ORs) of reporting pain at 3, 7, 30, or 90 days after ED discharge, using multiple imputation to account for missing outcome data. We controlled for clinical, demographic, and institutional factors and used weighting to account for the propensity to be prescribed an opioid analgesic at ED discharge.ResultsAmong 2413 adult ED patients with suspected urolithiasis, 62% reported persistent pain 3 days after discharge. Participants prescribed an opioid analgesic at discharge were OR 2.51 (95% confidence interval [CI] 1.82-3.46) more likely to report persistent pain than those without a prescription. Those who reported using opioid analgesics 3 days after discharge were OR 2.24 (95% CI 1.77-2.84) more likely to report pain at day 7 than those not using opioid analgesics at day 3, and those using opioid analgesics at day 30 had OR 3.25 (95% CI 1.96-5.40) greater odds of pain at day 90.ConclusionsOpioid analgesic prescription doubled the odds of persistent pain among ED patients with suspected urolithiasis. Limiting opioid analgesic prescribing at ED discharge for these patients might prevent persistent pain in addition to limiting access to these medications.

IntroductionEnhanced recovery after surgery (ERAS) pathways have emerged as a promising strategy to reduce postoperative opioid use and decrease the risk of developing new persistent opioid use in surgical patients. However, the association between ERAS implementation and discharge opioid prescribing practices is unclear.Study designWe conducted a retrospective observational quasi-experimental study of opioid-naïve patients aged 18+ undergoing cesarean delivery between February 2015 and December 2019 at a large academic center. An interrupted time series analysis (ITSA) was used to model the changes in pain medication prescribing associated with the implementation of ERAS to account for pre-existing temporal trends.ResultsAmong the 1473 patients (out of 2249 total) who underwent cesarean delivery after ERAS implementation, 80.72% received a discharge opioid prescription vs. 95.36% at baseline. Pre-ERAS daily oral morphine equivalents (OME) on the discharge prescription decreased by 0.48 OME each month (p

BackgroundOpioids and multimodal analgesia are widely administered to manage postoperative pain. However, little is known on how improvements in inpatient pain control are correlated with high-risk (> 90 daily OME) discharge opioid prescriptions for opioid naïve surgical patients.MethodsWe conducted a retrospective observational study of adult opioid-naïve patients undergoing surgery from June 2012 through December 2018 at a large academic medical center. We used multivariate logistic regression to assess whether multimodal analgesic drugs consumed in the 24 h prior to discharge was associated with a reduction in high-risk opioid discharge prescriptions. We identified other risk factors for receiving a high-risk discharge opioid prescription.ResultsAmong the 32,511 patients, 83% of patients were discharged with an opioid prescription. In 2013, 34.1% of patients with a discharge opioid prescription received a high-risk prescription and this declined to 17.7% by 2018. Use of multimodal analgesic agents during the final 24 h of hospitalization increased each year, with over 80% receiving at least one multimodal analgesic agent by 2018. The median OME consumed in the 24 h prior to discharge peaked in 2013 at 31 and steadily decreased to 19.8 by 2018. There was a significant association between the use of acetaminophen in the 24 h prior to discharge and a high-risk prescription at discharge (p < 0.01). OMEs consumed in the 24 h prior to discharge was a significant predictor of receiving a high-risk discharge prescription, even at low doses. Other factors associated with receipt of a high-risk discharge opioid prescription included male gender, race, history of anxiety disorder, and discharge service.DiscussionUse of multimodal analgesia regimens in hospitalized surgical patients in the 24 h prior to hospital discharge increased between 2012 and 2018. Simultaneously, opioid use prior to hospital discharge decreased. Despite these gains, approximately one in five discharge prescriptions was high-risk (> 90 daily OME). In addition, we found that prescribing of discharge opioids above inpatient opioid requirements remains common in opioid naive surgical patients.ConclusionProviders should account for pre-discharge opioid consumption and use of multimodal analgesia when considering the total and daily OME's that may be appropriate for an individual surgical patient on the discharge opioid prescription.

ObjectiveTo assess provider and practice characteristics that drive opioid prescription behavior using the American Urological Association census data.MethodsStratified weighted analysis using 1,157 census samples was performed to represent 12,660 urologists who practiced in the United States in 2018. We compared urologists according to their opioid prescription patterns to evaluate factors and motivations behind opioid use in the post-operative setting.ResultsOverall, 11,205 (88.5%) urologists prescribe opioids in the post-operative setting. The presence of procedure-specific institutional prescribing guidelines was associated with a greater tendency to prescribe ≤10 pills, and lesser tendency to prescribe 11 to 49 and ≥50 tablets following open abdominal (P = .003), laparoscopic (P < .001), scrotal (P < .001), and endoscopic surgeries (P < .001). The presence of institutional prescribing guidelines was associated with decreasing opioid prescriptions over a three-year period whereas not having guidelines was associated with an unchanged prescription practice over time. Basing current prescriptions on what was given to prior patients was reported by 85% and was more likely to result in an unchanged amount of prescriptions over time (29.2% vs 13.3%, P = .007). Motivations to avoid patient phone calls were reported by 23.8% and were more likely to increase the opioids provided within the next 3 years (3.2% vs 0.1%, P < .001).ConclusionPractitioners who endorsed using institutional guidelines prescribed fewer opioids following all types of surgery and were more likely to decrease their prescription behavior over time. This data supports continued efforts to provide urologists with more evidence-based guidance on best practice opioid prescribing in the future.

BackgroundPrevious reports on healthcare costs and expenditures associated with populations prescribed an opioid primarily focused on populations who chronically use opioids or have opioid use disorder. However, studies that characterize the healthcare and expenditures costs among the wider number of people prescribed opioids in a nationally representative population are unavailable. We sought to characterize the healthcare costs and expenditures associated with a population prescribed an opioid in the U.S. from 2008 to 2017.MethodsA serial cross-sectional design was used to compare the economic burden of adult household respondents who were prescribed and not prescribed an opioid using pooled data from the Medical Expenditure Panel Survey (MEPS) between 2008 and 2017. Respondents with an opioid prescription were matched to respondents without an opioid prescription using propensity score match methods with survey weights. Two-part generalized linear models were used to estimate the survey-weighted annual healthcare expenditures and resource utilization adjusting for multiple covariates. Additionally, 10-year trend comparisons between the groups were performed. Costs were adjusted to 2019 US dollars.ResultsThere was a weighted total of 31,696,671 respondents with an opioid and 31,536,639 respondents without an opioid after propensity score matching. The sample had a mean (SD) age of 50.63 years (18.03), 58.9% females, and 81.6% Whites. Total annual economic burden among RPOs was $524 billion. Annual total expenditures per respondent with and without an opioid were $16,542 and $7067, respectively (P

The growing prevalence of opioid use disorder (OUD) constitutes an urgent health crisis. Ample evidence indicates that risk for OUD is heritable. As a surrogate (or proxy) for OUD, we explored the genetic basis of using prescription opioids 'not as prescribed'. We hypothesized that misuse of opiates might be a heritable risk factor for OUD. To test this hypothesis, we performed a genome-wide association study (GWAS) of problematic opioid use (POU) in 23andMe research participants of European ancestry (N = 132,113; 21% cases). We identified two genome-wide significant loci (rs3791033, an intronic variant of KDM4A; rs640561, an intergenic variant near LRRIQ3). POU showed positive genetic correlations with the two largest available GWAS of OUD and opioid dependence (rg = 0.64, 0.80, respectively). We also identified numerous additional genetic correlations with POU, including alcohol dependence (rg = 0.74), smoking initiation (rg = 0.63), pain relief medication intake (rg = 0.49), major depressive disorder (rg = 0.44), chronic pain (rg = 0.42), insomnia (rg = 0.39), and loneliness (rg = 0.28). Although POU was positively genetically correlated with risk-taking (rg = 0.38), conditioning POU on risk-taking did not substantially alter the magnitude or direction of these genetic correlations, suggesting that POU does not simply reflect a genetic tendency towards risky behavior. Lastly, we performed phenome- and lab-wide association analyses, which uncovered additional phenotypes that were associated with POU, including respiratory failure, insomnia, ischemic heart disease, and metabolic and blood-related biomarkers. We conclude that opioid misuse can be measured in population-based cohorts and provides a cost-effective complementary strategy for understanding the genetic basis of OUD.

The opioid epidemic was triggered by an overprescription of opioid analgesics. In the treatment of chronic pain, repeated opioid administrations are required which ultimately lead to tolerance, physical dependence, and addiction. A possible way to overcome this conundrum consists of a co-medication that maintains the analgesic benefits of opioids while preventing their adverse liabilities. YHS, the extract of the plant Corydalis yanhusuo, has been used as analgesic in traditional Chinese medicine for centuries. More recently, it has been shown to promote analgesia in animal models of acute, inflammatory, and neuropathic pain. It acts, at least in part, by inhibiting the dopamine D2 receptor, suggesting that it may be advantageous to manage addiction. We first show that, in animals, YHS can increase the efficacy of morphine antinociceptive and, as such, decrease the need of the opioid. We then show that YHS, when coadministered with morphine, inhibits morphine tolerance, dependence, and addiction. Finally, we show that, in animals treated for several days with morphine, YHS can reverse morphine dependence and addiction. Together, these data indicate that YHS may be useful as a co-medication in morphine therapies to limit adverse morphine effects. Because YHS is readily available and safe, it may have an immediate positive impact to curb the opioid epidemic.

Background and purposeThe extra medical use of, and addiction to, prescription opioid analgesics is a growing health problem. To characterize how prescription opioid abuse develops, this study investigated the affective consequences of escalating prescription opioid use using intracranial self-stimulation (ICSS) reward and oxycodone intravenous self-administration (IVSA) models.Experimental approachMale Wistar rats were given access to oxycodone IVSA (0.15 mg·kg-1 per infusion, i.v.) in short-access (ShA; 1 h) or long-access (LgA; 12 h) sessions for five sessions per week followed by intermittent 60-h discontinuations from drug access, a novel explicit test of the negative reinforcement hypothesis. Separate groups were first trained in the ICSS procedure and then in oxycodone IVSA in 11-h LgA sessions.Key resultsRats given LgA to oxycodone escalated their responding more than ShA rats, with further significant increases observed following each 60-h discontinuation. Presession brain reward thresholds increased with sequential daily LgA IVSA sessions, consistent with a growing negative affective state consequent to successive daily intoxication/abstinence cycles. A 1-h oxycodone IVSA interval was sufficient to normalize these elevated reward thresholds, as was, paradoxically, a 60-h weekend abstinence. The increase in ICSS thresholds was attenuated in a group treated with the long-acting κ-opioid antagonist norbinaltorphimine prior to IVSA training.Conclusion and implicationsChanges in brain reward function during escalation of oxycodone self-administration are driven by an interplay between κ-opioid receptor-mediated negative affective state associated with escalated oxycodone intake and dynamic restoration of brain reward status during longer periods of abstinence.

Preventing opioid misuse and opioid use disorder is critical among at-risk adolescents and young adults (AYAs). An Emergency Department (ED) visit provides an opportunity for delivering interventions during a rapidly changing opioid landscape. This paper describes pilot data and the protocol for a 2 × 2 factorial randomized controlled trial testing efficacy of early interventions to reduce escalation of opioid (prescription or illicit) misuse among at-risk AYAs. Interventions are delivered using technology by health coaches. AYAs ages 16-30 in the ED screening positive for prescription opioid use (+ ≥ 1 risk factor) or opioid misuse will be stratified by risk severity, sex, and age group. Participants will be randomly assigned to a condition at intake, either a live video health coach-delivered single session or a control condition of an enhanced usual care (EUC) community resource brochure. They are also randomly assigned to one of two post-intake conditions: health coach-delivered portal-like messaging via web portal over 30 days or EUC delivered at 30 days post-intake. Thus, the trial has four groups: health coach-delivered session+portal, health coach-delivered session+EUC, EUC + portal, and EUC + EUC. Outcomes will be measured at 3-, 6-, and 12-months. The primary outcome is opioid misuse based on a modified Alcohol Smoking and Substance Involvement Screening Test. Secondary outcomes include other opioid outcomes (e.g., days of opioid misuse, overdose risk behaviors), other substance misuse and consequences, and impaired driving. This study is innovative by testing the efficacy of feasible and scalable technology-enabled interventions to reduce and prevent opioid misuse and opioid use disorder. Trial Registration:ClinicalTrials.gov University of Michigan HUM00177625 NCT Registration: NCT04550715.

ObjectivesOpioid use disorder remains undertreated in the United States. One of the primary mechanisms for expanding access to treatment has been the use of buprenorphine. In this study, we compare prescribing trends of buprenorphine paid through Medicaid versus other payer sources.MethodsCombined data from California's prescription drug monitoring program and California's Department of Health Care Services was used to obtain statewide quarterly prescription rates for buprenorphine, indicated for the treatment of opioid use disorder, from 2012 to 2018.ResultsFrom 2012 to 2018, the rate of individuals treated with buprenorphine in Medicaid increased by 657% (1.39-10.5 Medicaid beneficiaries per 10,000) with increases beginning in 2014 and continuing through 2018. Rate of individual prescribing among non-Medicaid sources increased by 93.7% (6.54-12.7 non-Medicaid individuals per 10,000) with most increases occurring before 2014.ConclusionsCalifornia Medicaid has made considerable gains in buprenorphine access, with access growing steadily even after expansions through the Affordable Care Act plateaued. In contrast, recent gains in buprenorphine access for individuals without Medicaid are uninspiring, indicating that initiatives to improve buprenorphine access to patients without Medicaid are urgently needed.

BackgroundIn response to the opioid crisis, states and health systems are encouraging clinicians to use risk mitigation strategies aimed at assessing a patient's risk for opioid misuse or abuse: opioid agreements, prescription drug monitoring programs (PDMPs), and urine drug tests (UDT). Objective: The objective of this qualitative study was to understand how clinicians perceived and used risk mitigation strategies for opioid abuse/misuse and identify barriers to implementation. Methods: We interviewed clinicians who prescribe opioid medications in the outpatient setting from 2016-2018 and analyzed the data using Constructivist Grounded Theory methodology. Results: We interviewed 21 primary care clinicians and 12 specialists. Nearly all clinicians reported using the PDMP. Some clinicians (adopters) found the opioid agreement and UDTs to be valuable, but most (non-adopters) did not. Adopters found the agreements and UDTs helpful in treating patients equitably, setting limits, and having objective evidence of misuse; protocols and workflows facilitated the use of the strategies. Non-adopters perceived the strategies as awkward, disruptive to the clinician-patient relationship, and introducing a power differential; they also cited lack of time and resources as barriers to use. Conclusions: Our study demonstrates that clinicians in certain settings have found effective ways to implement and use the PDMP, opioid agreements, and UDT but that other clinicians are less comfortable with their use. Administrators and policymakers should ensure that the strategies are designed in a way that strengthens the clinician-patient relationship while maximizing safety for patients and that clinicians are adequately trained and supported when introducing the strategies.

BackgroundIn the past two decades, the U.S. saw an alarmingly increasing trend of benzodiazepine prescribing. Mandatory use of Prescription Drug Monitoring Programs (PDMPs) was suggested to have the potential to reduce opioid prescribing, but little is known about its impacts on benzodiazepines. This study examined whether PDMP data use mandates were associated with changes in benzodiazepine prescribing in the U.S. Methods: Aggregate state quarterly prescription drug records of benzodiazepines for Medicaid enrollees during 2010-2017 were obtained from the U.S. Medicaid State Drug Utilization Data. Three population-adjusted outcome variables were evaluated, including quantity, dosage, and Medicaid spending of benzodiazepine prescriptions per quarter per 100 Medicaid enrollees. The primary policy variable was the state-wide implementation of PDMP data use mandates for benzodiazepines. To account for between-state variations in mandates, an additional policy variable was considered to indicate strong mandates on PDMP data use, which required all prescribers to query a patient's PDMP records for first prescribing and subsequent prescribing at least every 12 months. Linear regressions with difference-in-difference approach were used to assess the associations between PDMP data use mandates and benzodiazepine prescribing, controlling for state-level time-varying policy and socioeconomic covariates. Results: The state-wide implementation of PDMP data use mandates for benzodiazepines was not associated with quantity, dosage, or Medicaid spending of benzodiazepine prescriptions. Strong mandates on PDMP data use were not associated with any benzodiazepine prescribing outcomes, either. Conclusions: There was no evidence for the associations between PDMP data use mandates for benzodiazepines and changes in benzodiazepine prescribing among Medicaid enrollees. Future research is warranted to replicate the study in other populations using individual patient records and continuously monitor the trends in benzodiazepine prescribing in association with PDMPs.

It is estimated that nearly a third of people who abuse drugs started with prescription opioid medicines. Approximately, 11.5 million Americans used prescription drugs recreationally in 2016, and in 2018, 46,802 Americans died as the result of an opioid overdose, including prescription opioids, heroin, and illicitly manufactured fentanyl (National Institutes on Drug Abuse (2020) Opioid Overdose Crisis. https://www.drugabuse.gov/drugs-abuse/opioids/opioid-overdose-crisis . Accessed 06 June 2020). Yet physicians will continue to prescribe oral opioids for moderate-to-severe pain in the absence of alternative therapeutics, underscoring the importance in understanding how drug choice can influence detrimental outcomes. One of the opioid prescription medications that led to this crisis is oxycodone, where misuse of this drug has been rampant. Being one of the most highly prescribed opioid medications for treating moderate-to-severe pain as reflected in the skyrocketed increase in retail sales of 866% between 1997 and 2007, oxycodone was initially suggested to be less addictive than morphine. The false-claimed non-addictive formulation of oxycodone, OxyContin, further contributed to the opioid crisis. Abuse was often carried out by crushing the pills for immediate burst release, typically by nasal insufflation, or by liquefying the pills for intravenous injection. Here, we review oxycodone pharmacology and abuse liability as well as present the hypothesis that oxycodone may exhibit a unique pharmacology that contributes to its high likability and abuse susceptibility. We will discuss various mechanisms that likely contribute to the high abuse rate of oxycodone including clinical drug likability, pharmacokinetics, pharmacodynamics, differences in its actions within mesolimbic reward circuity compared to other opioids, and the possibility of differential molecular and cellular receptor interactions that contribute to its selective effects. We will also discuss marketing strategies and drug difference that likely contributes to the oxycodone opioid use disorders and addiction.

BackgroundThe rise in opioid-related mortality and opioid-related emergency department (ED) visits has stimulated research on whether broader economic declines, such as the Great Recession, affect opioid-related morbidity. We examine in New York City whether one measure of morbidity-opioid-related ED visits-responded acutely to the large negative "shock" of the Great Recession.MethodsData comprise outpatient "treat and release" opioid-related ED visits in New York City for the 72 months spanning January 2006 to December 2011, taken from the Statewide Emergency Department Database (n = 150,246). We modeled the monthly incidence of opioid-related ED visits using Autoregressive, Integrated, Moving Average (ARIMA) time-series methods to control for patterning in ED visits before examining its potential association with the economic shock of the Great Recession.ResultsNew York City shows a mean of 1761 outpatient ED visits per month for opioid dependence and abuse. Unexpectedly large drops in employment coincide with fewer than expected opioid dependence and abuse ED visits in that same month. The result (coefficient = 0.046, 95% Confidence Interval [CI]: 0.002, 0.090) represents a 0.8% drop in overall incidence of opioid dependence and abuse ED visits during the Great Recession. We, however, observe no association between the Great Recession and ED visits for prescription opioid overdose or heroin overdose, or with inpatient ED visits for opioid dependence and abuse.ConclusionsFindings, if replicated, indicate distinct short-term reductions in opioid-related morbidity following the Great Recession. This result diverges from previous findings of increased opioid use following extended economic downturns.