Improving Naloxone Co-prescribing Through Clinical Decision Support.

BACKGROUND: Despite national guidelines recommending naloxone co-prescription with high-risk medications, rates remain low nationally. This was reflected at our institution with remarkably low naloxone prescribing rates. We sought to determine if a clinical decision support (CDS) tool could increase rates of naloxone co-prescribing with high-risk prescriptions. METHODS:  An alert in the electronic health record was triggered upon signing an order for a high-risk opioid medication without a naloxone co-prescription. We examined all opioid prescriptions written by family and general internal medicine practitioners at the University of Iowa Hospitals and Clinics in outpatient encounters between November 30, 2020, and February 28, 2022. Once triggered by a high-risk prescription, the CDS tool had the option to choose an order set with an automatically selected co-prescription for naloxone along with patient instructions automatically added to the patient's after-visit summary (AVS). We examined the monthly percentage of patients receiving Schedule II opioid prescriptions ≥90 morphine milliequivalents (MME)/day who received concurrent naloxone prescriptions in the 12 months before the CDS went live and the three months following go-live. RESULTS:  Concurrent naloxone prescriptions increased from 1.1% in the 12 months prior to implementation in November 2021 to 9.4% (p<0.001) during the post-intervention period across eight family medicine and internal medicine clinics. DISCUSSION:  This single-center quality improvement project with retrospective analysis demonstrates the potential efficacy of a single CDS tool in increasing the rate of naloxone prescription. The impact of such prescribing on overall mortality requires further research. CONCLUSIONS: The CDS tool was easy to implement and improved rates of appropriate naloxone co-prescribing.

Understanding Clinician Knowledge, Attitudes, and Practices Relating to Nonpharmaceutical Fentanyl and Harm Reduction.

BACKGROUND: Nonpharmaceutical fentanyl (NPF) is driving the national epidemic of opioid overdose deaths. Clinicians can play a role in fostering awareness of this growing risk and delivering interventions to reduce mortality. However, there is limited research assessing clinician knowledge, attitudes, and practices relating to NPF and harm reduction strategies. METHODS: A 34-question survey was designed to assess knowledge, attitudes, and practices related to NPF and harm reduction strategies of adult and pediatric hospital-based and emergency clinicians at a single academic medical center. Results were summarized using descriptive statistics. Chi square and Fishers exact tests were used to compare groups. RESULTS: There were 136 survey responses. The majority (88%) of respondents correctly answered a question on NPF potency. Most respondents were aware that NPF exposure was very (84%) or somewhat likely (10%) for someone using illicit opioids and very (44%) or somewhat likely (46%) for nonopioid drugs. Respondents viewed overdose prevention as highly important for patients using illicit opioids (93%) and nonopioid drugs (86%) but few (21%) were very/extremely familiar with overdose prevention strategies and just over half (57%) were comfortable/very comfortable counseling about overdose prevention. There was wide variability in utilization of harm reduction/treatment strategies (7.3% frequently providing fentanyl test kits to 70% frequently prescribing naloxone). Higher levels of comfort and familiarity with overdose prevention were associated with more frequent counseling on harm reduction strategies. Pediatric-only clinicians had less familiarity (5% very/extremely familiar) and comfort (35% comfortable/very comfortable) with overdose prevention, and limited use of harm reduction strategies (0%-31% using each strategy frequently). CONCLUSIONS: While clinicians had knowledge and awareness of NPF and rated overdose prevention as highly important, utilization of harm reduction and treatment strategies was variable. This study highlights opportunities for education and system-based support to improve clinician-driven harm reduction practices for patients at risk of overdose.

Effects of Online Naloxone Training for Laypersons: An Extended-Baseline Assessment.

Background: While laypersons can play a crucial role in administering naloxone in opioid overdoses, they must be recruited and trained to effectively manage overdose events as good Samaritans. This study aimed to examine the effectiveness of a technology-based intervention that recruited and trained laypersons to administer naloxone. Methods: Opioid Rapid Response System (ORRS) was an online recruitment and training intervention which capitalized on social cognitive theory and a digital media engagement model to mobilize laypersons to administer intranasal naloxone. ORRS was developed based on a randomized waitlisted controlled trial (N = 220). This secondary analysis is a within-group, extended-baseline assessment of the waitlisted group (n = 106), considering that they served as their own control prior to receiving the training. ORRS was conducted in five counties of Indiana with adults who did not self-identify as a certified first responder. Five indices were generated from 23 variables: knowledge of overdose signs, knowledge of overdose management, self-efficacy in responding, concerns about responding, and intent to respond. Paired t-test compared changes between 3 timepoints. Results: Three indices had significantly greater increases associated with training compared to extended baseline: recognizing opioid overdose signs (difference = 0.08; 95%CI = 0.02, 0.15; t = 2.48; p = 0.01); knowledge of overdose management (difference = 0.27; 95%CI = 0.18, 0.35; t = 5.99; p < 0.01); and self-efficacy in overdose management (difference = 0.68; 95%CI = 0.45, 0.91; t = 5.78; p < 0.01). Concerns related to overdose management significantly decreased as expected (difference = -1.53; 95%CI = -1.86, -1.21; t = -9.27; p < 0.01). Conclusions: ORRS provided strong support for self-efficacy, concerns, and knowledge related to overdose management, and the digital modality accelerates largescale dissemination.

Quantifying the Burden of Opioid Use Disorder and Non-fatal Opioid Overdose in American Indian and Alaskan Native Populations Using the Cerner Real-World Data™ Database.

OBJECTIVE: This study evaluated the prevalence and incidence of opioid use disorder (OUD), rates of opioid overdose (OD), and rates of non-fatal (NF) OD in American Indian/Alaskan Native (AI/AN) populations. METHODS: We used de-identified patient data from Oracle Cerner Real-World Data™. Rates were estimated over time, and stratified by sex, age, marital status, insurance, and region. Mann-Kendall trend tests and Theil-Sen slopes assessed changes over time for each group while autoregressive modeling assessed differences between groups. RESULTS: The study identified trends in OUD and OD among 700,225 AI/AN patients aged 12 and above. Between 2012 and 2022, there was a significant upward trend in both OUD and OD rates (p < 0.05) , with OUD diagnosed in 1.75% and OD in 0.38% of the population. The Western region of the US exhibited the highest rates of OUD and OD. The 35-49 age group showed the highest rates of OUD, while the 12-34 age group had the highest rates of OD. Marital status analysis revealed higher rates of OUD and OD among separated, widowed, or single patients. Additionally, individuals with Medicare or Medicaid insurance demonstrated the highest rates of OUD and OD. CONCLUSION: Results show that rates of OUD, OD, and NF OD continue to rise among AI/AN individuals, with some regional and demographic variation. Our study provides foundational estimates of key AI/AN populations bearing greater burdens of opioid-related morbidity that federal, state, and tribal organizations can use to direct and develop targeted resources that can improve the health and well-being of AI/AN communities.

Prevalence of fentanyl in the pediatric postmortem population from 2019 to 2023.

For the past decade, illicitly manufactured fentanyl has been a primary contributor in drug overdose deaths regardless of age. The pediatric population is particularly vulnerable to fentanyl exposure, yet there are limited case reports involving this population. Postmortem cases from 2019 to 2023 were retrospectively analyzed to determine the prevalence of fentanyl in decedents between 0 and 12 years of age. Over this time frame, the fentanyl positivity rate increased from 2.6 to 6.2% (n = 632). The most commonly reported age group was 0-4 years, with a peak around 1 year of age for toddlers. Fentanyl concentrations in blood (n = 573) ranged from 0.19 to 360 ng/mL (mean 18 ng/mL, median 6.9 ng/mL). Polydrug use was present in 428 cases; midazolam (n = 96) and methamphetamine (n = 66) were the most common drugs found concurrently in blood with fentanyl, followed by markers of illicitly manufactured fentanyl, such as xylazine (n = 23), para-fluorofentanyl (n = 18), and acetyl fentanyl (n = 17). This report contrasts the differences in postmortem pediatric fentanyl toxicology results for three groups of case histories: likely medical intervention (n = 113), pregnancy/birth related (n = 136), and inadvertent/intentional exposure (n = 196). Overall, this study provides a retrospective review of postmortem pediatric fentanyl concentrations in a variety of biological matrices and highlights the need for comprehensive toxicology testing in postmortem pediatric casework.

Chronic pain and accidental acute toxicity deaths in Canada, 2016-2017. / Recherche quantitative originale La douleur chronique et les décès par intoxication aiguë accidentelle au Canada, 2016-2017.

INTRODUCTION: Multiple Canadian jurisdictions have reported a pattern of chronic pain among people who died from substance-related acute toxicity. This study examined the prevalence and characteristics of those with chronic pain using data from a national study of people who died of accidental acute toxicity. METHODS: A cross-sectional analysis of accidental substance-related acute toxicity deaths that occurred in Canada between 1 January 2016 and 31 December 2017 was conducted. The prevalence of pain and pain-related conditions were summarized as counts and percentages of the overall sample. Subgroups of people with and without a documented history of chronic pain were compared across sociodemographic characteristics, health history, contextual factors and substances involved. RESULTS: From the overall sample (n = 7902), 1056 (13%) people had a history of chronic pain while 6366 (81%) had no documented history. Those with chronic pain tended to be older (40 years and older), unemployed, retired and/or receiving disability supports around the time of death. History of mental health conditions, trauma and surgery or injury was significantly more prevalent among people with chronic pain. Of the substances that most frequently contributed to death, opioids typically prescribed for pain (hydromorphone and oxycodone) were detected in toxicology more often among those with chronic pain than those without. CONCLUSION: Findings underscore the cross-cutting role of multiple comorbidities and unmanaged pain, which could compound the risk of acute toxicity death. Continued prioritization of harm reduction and regular patient engagement to assess ongoing needs are among the various opportunities for intervention.

Fentanyl and xylazine crisis: Crafting coherent strategies for opioid overdose prevention.

The United States is in the throes of a severe opioid overdose epidemic, primarily fueled by the pervasive use of fentanyl and the emerging threat of xylazine, a veterinary sedative often mixed with fentanyl. The high potency and long duration of fentanyl is compounded by the added risks from xylazine, heightening the lethal danger faced by opioid users. Measures such as enhanced surveillance, public awareness campaigns, and the distribution of fentanyl-xylazine test kits, and naloxone have been undertaken to mitigate this crisis. Fentanyl-related overdose deaths persist despite these efforts, partly due to inconsistent policies across states and resistance towards adopting harm reduction strategies. A multifaceted approach is imperative in effectively combating the opioid overdose epidemic. This approach should include expansion of treatment access, broadening the availability of medications for opioid use disorder, implementation of harm reduction strategies, and enaction of legislative reforms and diminishing stigma associated with opioid use disorder.

Need for strategic communications and stakeholder engagement to advance acceptability of an overdose preventing vaccine targeting fentanyl.

BACKGROUND: Fentanyl is a synthetic opioid, exposure to which has led to hundreds of thousands of overdose deaths. Novel vaccines are being developed that might protect against fentanyl overdose. Proactive attention to strategic communications and stakeholder engagement may smooth uptake of a novel vaccine given known challenges around vaccine hesitancy and concern for stigma related to substance use. METHODS: Qualitative interviews (N = 74) with a purposive sample of adolescents/young adults with opioid use disorder (OUD), family members of persons with OUD, experts in substance use treatment and harm reduction, and community members were conducted and thematically analyzed to discern attitudes toward a fentanyl vaccine, and directions for communications and engagement. RESULTS: Major themes reflected personal concerns for biomedical risk and system-level concerns for alignment and integration of an overdose preventing vaccine with prevailing beliefs about addiction and associated frameworks and philosophies for treatment and response. CONCLUSION: Acceptability and implementation of a novel fentanyl vaccine targeting overdose will need precision communications that address biomedical, moral/spiritual, and structural perspectives about the nature of addiction. Education about the purpose and limits of a fentanyl vaccine, partnerships with diverse stakeholders from throughout the opioid response ecosystem and interweaving of a vaccine strategy into comprehensive prevention and treatment are recommended.

Sensitivity and specificity of International Classification of Diseases algorithms (ICD-9 and ICD-10) used to identify opioid-related overdose cases: A systematic review and an example of estimation using Bayesian latent class models in the absence of gold standards.

OBJECTIVES: This study aimed to summarize validity estimates of International Classification of Diseases (ICD) codes in identifying opioid overdose (OOD) among patient data from emergency rooms, emergency medical services, inpatient, outpatient, administrative, medical claims, and mortality, and estimate the sensitivity and specificity of the algorithms in the absence of a perfect reference standard. METHODS: We systematically reviewed studies published before December 8, 2023, and identified with Medline and Embase. Studies reporting sufficient details to recreate a 2 × 2 table comparing the ICD algorithms to a reference standard in diagnosing OOD-related events were included. We used Bayesian latent class models (BLCM) to estimate the posterior sensitivity and specificity distributions of five ICD-10 algorithms and of the imperfect coroner's report review (CRR) in detecting prescription opioid-related deaths (POD) using one included study. RESULTS: Of a total of 1990 studies reviewed, three were included. The reported sensitivity estimates of ICD algorithms for OOD were low (range from 25.0% to 56.8%) for ICD-9 in diagnosing non-fatal OOD-related events and moderate (72% to 89%) for ICD-10 in diagnosing POD. The last included study used ICD-9 for non-fatal and fatal and ICD-10 for fatal OOD-related events and showed high sensitivity (i.e. above 97%). The specificity estimates of ICD algorithms were good to excellent in the three included studies. The misclassification-adjusted ICD-10 algorithm sensitivity estimates for POD from BLCM were consistently higher than reported sensitivity estimates that assumed CRR was perfect. CONCLUSION: Evidence on the performance of ICD algorithms in detecting OOD events is scarce, and the absence of bias correction for imperfect tests leads to an underestimation of the sensitivity of ICD code estimates.

RéSUMé: OBJECTIFS: Cette étude avait pour objectifs de recenser les estimations de la validité des codes de Classification Internationale des Maladies (CIM) à diagnostiquer les cas de surdose aux opioïdes (SDO) chez des patients en utilisant les données de salles d'urgence, services médicaux d'urgence, hospitalisations, soins ambulatoires, services administratifs, demandes de remboursement de frais médicaux, ainsi que de mortalité, et d'estimer la sensibilité et la spécificité d'algorithmes utilisant la CIM en l'absence d'un test de référence parfait. MéTHODES: Nous avons examiné systématiquement les études publiées avant le 8 décembre 2023, et identifiées dans Medline et Embase. Les études rapportant suffisamment de détails permettant de recréer un tableau 2 × 2 comparant les algorithmes de la CIM à un test de référence pour le diagnostic d'événements liés aux SDO ont été incluses. Les données d'une étude éligible ont été utilisées pour estimer, avec des modèles Bayésiens de classes latentes (MBCL), les distributions a posteriori de la sensibilité et de la spécificité de cinq algorithmes de la CIM-10 et du test imparfait de révision du rapport du coroner (RRC) dans la détection des décès liés aux opioïdes de prescription (DOP). RéSULTATS: Trois parmi les 1 990 études examinées ont été retenues. Les estimations rapportées de la sensibilité des codes CIM étaient faibles (variant de 25,0 % à 56,8 %) pour CIM-9 dans le diagnostic des événements liés aux SDO non-fatales dans une étude, et modérées (72 % à 89 %) pour CIM-10 dans le diagnostic des DOP dans une autre étude. La dernière étude incluse combinait des codes CIM-9 pour les cas non-fatals et fatals et CIM-10 pour les cas fatals et démontrait des estimations de sensibilité élevées (c.à.d. supérieures à 97 %). Les estimations de la spécificité étaient bonnes à excellentes dans les trois études. Les estimations de la sensibilité des algorithmes de la CIM-10 corrigées pour les erreurs de classification pour les décès liés aux opioïdes, obtenues à partir de nos MBCL, étaient systématiquement plus élevées que celles rapportées et qui supposaient que RRC était un test parfait. CONCLUSION: Les évidences sur la performance des algorithmes de la CIM dans la détection des cas de SDO sont rares, et l'absence de correction de biais pour des tests diagnostiques imparfaits conduit à une sous-estimation de la sensibilité des codes de la CIM.

Spatial co-occurrence of firearm homicides and opioid overdose deaths in Chicago by level of COVID-19 mortality, 2017-2021.

BACKGROUND: Firearm homicide and opioid overdoses were already leading causes of death in the U.S. before both problems surged during the COVID-19 pandemic. Firearm violence, overdoses, and COVID-19 have all disproportionately harmed communities that are socially and economically marginalized, but the co-occurrence of these problems in the same communities has received little attention. To describe the co-occurrence of firearm homicides and opioid overdose deaths with COVID-19 mortality we used 2017-2021 medical examiner's data from Chicago, IL. Deaths were assigned to zip codes based on decedents' residence. We stratified zip codes into quartiles by COVID-19 mortality rate, then compared firearm homicide and fatal opioid overdose rates by COVID-19 quartile. FINDINGS: Throughout the study period, firearm homicide and opioid overdose rates were highest in the highest COVID-19 mortality quartile and lowest in the lowest COVID-19 mortality quartile. Increases in firearm homicide and opioid overdose were observed across all COVID-19 mortality quartiles. CONCLUSIONS: High co-occurrence of these deaths at the community level call for addressing the systemic forces which made them most vulnerable before the pandemic. Such strategies should consider the environments where people reside, not only where fatal injuries occur.

Trends in recurrent overdose and treatment initiation following emergency department visits for opioid overdose between 2016 and 2021.

BACKGROUND: Overdose remains a pressing public health concern in the United States, particularly with the emergence of fentanyl and other potent synthetic opioids in the drug supply. We evaluated trends in recurrent overdose and opioid use disorder (OUD) treatment initiation following emergency department (ED) visits for opioid overdose to inform response efforts. METHODS: This retrospective cohort study used electronic health record and statewide administrative data from Rhode Island residents who visited EDs for opioid overdose between July 1, 2016, and June 30, 2021, a period with fentanyl predominance in the local drug supply. The primary outcome was recurrent overdose in the 365 days following the initial ED visit. OUD treatment initiation within 180 days following the initial ED visit was considered as a secondary outcome. Trends in study outcomes were summarized by year of the initial ED visit. RESULTS: Among 1745 patients attending EDs for opioid overdose, 20 % (n=352) experienced a recurrent overdose within 365 days, and this percentage was similar by year (p=0.12). Among patients who experienced any recurrent overdose, the median time to first recurrent overdose was 88 days (interquartile range=23-208), with 85 % (n=299/352) being non-fatal. Among patients not engaged in OUD treatment at their initial ED visit, 33 % (n=448/1370) initiated treatment within 180 days; this was similar by year (p=0.98). CONCLUSIONS: Following ED visits for opioid overdose in Rhode Island from 2016-2021, the one-year risk of recurrent overdose and six-month treatment initiation rate remained stable over time. Innovative prevention strategies and improved treatment access are needed.

Effect of a peer-led emergency department behavioral intervention on non-fatal opioid overdose: 18-month outcome in the Navigator randomized controlled trial.

BACKGROUND AND AIMS: Emergency departments (EDs) provide an opportunity to identify people at risk of overdose and reduce the risk. We evaluated the effect of an ED behavioral intervention delivered by peer recovery support specialists (PRSSs) on non-fatal opioid overdose. DESIGN: Two-arm, randomized trial. SETTING: Two EDs in Rhode Island, USA. PARTICIPANTS: ED patients presenting with an opioid overdose, complications of opioid use disorder or a recent history of opioid overdose (November 2018-May 2021). Among 648 participants, the mean age was 36.9 years, 68.2% were male and 68.5% were White. INTERVENTION AND COMPARATOR: Participants were randomized to receive a behavioral intervention from a PRSS (n = 323) or a licensed clinical social worker (LICSW) (n = 325). PRSS and LICSW used evidence-based interviewing and intervention techniques, informed by their lived experience (PRSS) or clinical theory and practice (LICSW). MEASUREMENTS: We identified non-fatal opioid overdoses in the 18 months following the ED visit through linkage to statewide emergency medical services data using a validated case definition. The primary outcome was any non-fatal opioid overdose during the 18-month follow-up period. FINDINGS: Among 323 participants randomized to the PRSS arm, 81 (25.1%) had a non-fatal opioid overdose during follow-up, compared with 95 (29.2%) of 325 participants randomized to the LICSW arm (P = 0.24). There was no statistically significant difference in the effectiveness of randomization to the PRSS arm versus the LICSW arm on the risk of non-fatal opioid overdose, adjusting for the history of previous overdose (relative risk = 0.86, 95% confidence interval = 0.67-1.11). CONCLUSIONS: In Rhode Island, USA, over one-in-four emergency department patients at high risk of overdose experience a non-fatal opioid overdose in the 18 months post-discharge. We found no evidence that the risk of non-fatal opioid overdose differs for emergency department patients receiving a behavioral intervention from a peer recovery support specialist versus a licensed clinical social worker.

A Regional Survey of Attitudes and Experiences in Determining When to Prescribe Intranasal Naloxone for Patients Seen in Palliative Care Clinics in the United States of America.

Background: Published guidelines that help clinicians identify patients who would benefit from the co-prescription of intranasal naloxone (IN) exclude "palliative care patients." In the absence of clear care standards, palliative care (PC) clinicians may experience uncertainty in how to approach IN co-prescriptions. Objective: Explore the attitudes of PC clinicians in the United States of America who work at regional health care institutions regarding IN prescriptions for patients they prescribe opioids for. Methods: An 18-question electronic survey was distributed to PC clinicians that practice at institutions in Wisconsin or Minnesota with at least 10 other PC clinicians between February and May 2023. The survey explored clinical scenarios in which respondents would and would not prescribe IN. Results: Fifty-six PC clinicians responded to the survey-response rate 41%. Most respondents (90.9%) did not feel IN prescriptions should be reserved for patients with a full code status; 67.9% of respondents felt that IN prescriptions are reasonable for certain patients with a terminal illness and comfort goals of care. Neither prognosis, duration of opioid therapy, nor dose of opioid therapy were significant factors in determining whether most respondents prescribed IN for their patients. Most respondents (81.8%) felt clinician counseling and patient consent were essential before prescribing IN. Conclusion: Most PC clinicians in our survey felt that IN prescriptions can be appropriate for patients they prescribe opioids for. Bystander safety was an emerging rationale for why respondents chose to prescribe IN for their patients. Despite public health efforts to make IN more freely available, most respondents felt clinician counseling was essential before prescribing IN for their patients.

A theoretical explanation of naloxone provision among primary care physicians and community pharmacists in Tennessee.

BACKGROUND: Increasing access to naloxone reduces opioid-related morbidity and mortality. Primary care and community pharmacy settings are critical access points, yet limited theoretical research has examined naloxone prescribing and dispensing behaviors. OBJECTIVES: To determine if the theory of planned behavior (TPB) combined with theoretical constructs from communication science explains intentions to co-prescribe and discuss co-dispensing naloxone among primary care physicians and community pharmacists, respectively. METHODS: This cross-sectional study surveyed cohorts of licensed primary care physicians and community pharmacists in Tennessee in 2017. Intentions were measured using profession-specific case vignettes, whereby they were asked given 10 similar patients, how many times (0-10) would they co-prescribe or discuss co-dispensing naloxone. Bivariate and multivariable analyses were used. RESULTS: The analytic sample included 295 physicians (response rate = 15.6 %) and 423 pharmacists (response rate = 19.4 %). Approximately 65 % of physicians reported never intending to co-prescribe naloxone (0 out of 10 patients), while 47 % of pharmacists reported never intending to discuss co-dispensing. All TPB constructs-attitudes (AOR = 1.32, CI = 1.16-1.50), subjective norms (AOR = 1.17, CI = 1.06-1.30), and perceived behavioral control (AOR 1.16, CI = 1.02-1.33)-were associated with an increased likelihood of pharmacists always (versus never) discussing co-dispensing. Similarly, two TPB constructs-attitudes (AOR = 1.41, CI = 1.19-1.68) and subjective norms (AOR = 1.22, CI = 1.08-1.39)-were associated with an increased likelihood of physicians always co-prescribing. Among physicians only, one communication construct-self-perceived communication competence (AOR = 1.19, CI = 1.01-1.41)-was associated with an increased likelihood of always co-prescribing. CONCLUSION: Findings support the value of theory, particularly TPB, in explaining primary care physician intentions to co-prescribe and community pharmacist intentions to discuss co-dispensing naloxone.

From Friend to Foe: A Case of Naloxone-Induced Pulmonary Edema.

Naloxone, an opioid receptor antagonist, effectively reverses opioid overdose and opioid-induced respiratory depression. A few side effects were reported after naloxone administration, including arrhythmia and pulmonary edema. Although rare, naloxone-induced pulmonary edema can be a severe and sometimes life-threatening complication requiring mechanical ventilation. This condition is predominantly linked to an upsurge in catecholamines after opioid reversal as part of acute withdrawal syndrome, especially seen in patients who chronically use opioids. In this report, we present a case of a 66-year-old patient who developed pulmonary edema following the administration of multiple doses of intravenous and intranasal naloxone for opioid overdose. This case highlights the potential adverse effects associated with naloxone use and discusses how to employ this life-saving medication with minimal side effects.

State-level factors associated with implementation of prescription drug monitoring program integration and mandatory use policies, United States, 2009-2020.

BACKGROUND: Prescription drug monitoring programs (PDMPs) have been widely adopted as a tool to address the prescription opioid epidemic in the United States. PDMP integration and mandatory use policies are 2 approaches states have implemented to increase use of PDMPs by prescribers. While the effectiveness of these approaches is mixed, it is unclear what factors motivated states to implement them. This study examines whether opioid dispensing, adverse health outcomes, or other non-health-related factors motivated implementation of these PDMP approaches. METHODS: Time-to-event analysis was performed using lagged state-year covariates to reflect values from the year prior. Extended Cox regression estimated the association of states' rates of opioid dispensing, prescription opioid overdose deaths, and neonatal opioid withdrawal syndrome with implementation of PDMP integration and mandatory use policies from 2009 to 2020, controlling for demographic and economic factors, state government and political factors, and prior opioid policies. RESULTS: In our main model, prior opioid dispensing (HR 2.31, 95% CI 1.17, 4.57), neonatal opioid withdrawal syndrome hospitalizations (HR 1.55, 95% CI 1.09, 2.19), and number of prior opioid policies (HR 2.13, 95% CI 1.13, 4.00) were associated with mandatory use policies. Prior prescription opioid overdose deaths (HR 1.21, 95% CI 1.08, 1.35) were also associated with mandatory use policies in a model that did not include opioid dispensing or neonatal opioid withdrawal syndrome. No study variables were associated with implementation of PDMP integration. CONCLUSION: Understanding state-level factors associated with implementing PDMP approaches can provide insights into factors that motivate the adoption of future public health interventions.

Reducing perceived barriers to scaling up overdose education and naloxone distribution and medications for opioid use disorder in the United States in the HEALing (Helping End Addiction Long-Term®) communities study.

BACKGROUND: Scaling up overdose education and naloxone distribution (OEND) and medications for opioid use disorder (MOUD) is needed to reduce opioid overdose deaths, but barriers are pervasive. This study examines whether the Communities That HEAL (CTH) intervention reduced perceived barriers to expanding OEND and MOUD in healthcare/behavioral health, criminal-legal, and other/non-traditional venues. METHODS: The HEALing (Helping End Addiction Long-Term®) Communities Study is a parallel, wait-list, cluster randomized trial testing the CTH intervention in 67 communities in the United States. Surveys administered to coalition members and key stakeholders measured the magnitude of perceived barriers to scaling up OEND and MOUD in November 2019-January 2020, May-June 2021, and May-June 2022. Multilevel linear mixed models compared Wave 1 (intervention) and Wave 2 (wait-list control) respondents. Interactions by rural/urban status and research site were tested. RESULTS: Wave 1 respondents reported significantly greater reductions in mean scores for three outcomes: perceived barriers to scaling up OEND in Healthcare/Behavioral Health Venues (-0.26, 95% confidence interval, CI: -0.48, -0.05, p = 0.015), OEND in Other/Non-traditional Venues (-0.53, 95% CI: - 0.84, -0.22, p = 0.001) and MOUD in Other/Non-traditional Venues (-0.34, 95% CI: -0.62, -0.05, p = 0.020). There were significant interactions by research site for perceived barriers to scaling up OEND and MOUD in Criminal-Legal Venues. There were no significant interactions by rural/urban status. DISCUSSION: The CTH Intervention reduced perceived barriers to scaling up OEND and MOUD in certain venues, with no difference in effectiveness between rural and urban communities. More research is needed to understand facilitators and barriers in different venues.

Opioid Overdose-Induced Diffusion Restriction in the Bilateral Basal Ganglia Revealed on Brain Imaging.

Opioid misuse and addiction have led to an opioid epidemic in the United States, with widespread effects on the healthcare system. Opioid-induced cardiovascular morbidity and mortality effects have been extensively described in past literature; however, neurological effects have been described less frequently.  Here, we describe a case of a female patient who presented to our center after being found unresponsive with magnetic resonance imaging (MRI), revealing bilateral basal ganglia diffuse restriction hyperintensities secondary to a diagnosis of opioid overdose.  Opioid overdose-induced bilateral basal ganglia diffusion restriction has only been described infrequently in the literature. Recognizing the associated imaging findings as a potential consequence of opioid overdose is important to avoid unnecessary workups for ischemic stroke.

Racial/ethnic trends in opioid and polysubstance opioid overdose mortality in adolescents and young adults, 1999-2020.

OBJECTIVES: Previous reports have described variations in opioid overdose mortalities among different race/ethnicity groups. We have analyzed racial/ethnicity trends in opioid and polysubstance opioid overdose mortalities in adolescents and young adults to further characterize differences and potential sub-epidemics within this specific population. METHODS: We used mortality data from the U.S. Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (WONDER) Multiple Cause of Death file from 1999 to 2020. Drug overdose mortalities were identified using International Classification of Diseases, Tenth Revision (ICD-10) codes. Joinpoint regression was used to examine mortality rates for all opioids, opioids with a stimulant, opioids with benzodiazepines, and opioids with alcohol among racial/ethnic groups (non-Hispanic white, non-Hispanic Black, Hispanic, non-Hispanic other) in adolescents and young adults. RESULTS: The Average Annual Percent Change (AAPC) for mortality due to opioid and polysubstance opioid overdose increased for all racial/ethnic groups where data was available for analysis from 1999 to 2020. For mortality due to any opioid and any opioid with a stimulant, the greatest AAPC was seen among non-Hispanic Blacks. CONCLUSIONS: Unprecedented increases in mortality due to opioid overdose occurred in the last two decades among adolescents and young adults. Heterogenous trends support the notion that the previously defined opioid overdose epidemic "waves" may not accurately depict the effects of the crisis in all race/ethnicity groups. Additionally, alarming increases in opioid-stimulant overdose mortality starting in 2012 further characterize the interrelated effects of the third and fourth waves.