Machine learning identifies risk factors associated with long-term opioid use in fibromyalgia patients newly initiated on an opioid.

OBJECTIVES: Fibromyalgia is frequently treated with opioids due to limited therapeutic options. Long-term opioid use is associated with several adverse outcomes. Identifying factors associated with long-term opioid use is the first step in developing targeted interventions. The aim of this study was to evaluate risk factors in fibromyalgia patients newly initiated on opioids using machine learning. METHODS: A retrospective cohort study was conducted using a nationally representative primary care dataset from the UK, from the Clinical Research Practice Datalink. Fibromyalgia patients without prior cancer who were new opioid users were included. Logistic regression, a random forest model and Boruta feature selection were used to identify risk factors related to long-term opioid use. Adjusted ORs (aORs) and feature importance scores were calculated to gauge the strength of these associations. RESULTS: In this study, 28 552 fibromyalgia patients initiating opioids were identified of which 7369 patients (26%) had long-term opioid use. High initial opioid dose (aOR: 31.96, mean decrease accuracy (MDA) 135), history of self-harm (aOR: 2.01, MDA 44), obesity (aOR: 2.43, MDA 36), high deprivation (aOR: 2.00, MDA 31) and substance use disorder (aOR: 2.08, MDA 25) were the factors most strongly associated with long-term use. CONCLUSIONS: High dose of initial opioid prescription, a history of self-harm, obesity, high deprivation, substance use disorder and age were associated with long-term opioid use. This study underscores the importance of recognising these individual risk factors in fibromyalgia patients to better navigate the complexities of opioid use and facilitate patient-centred care.

Prenatal opioid exposure by likelihood of exposure and risk to prenatal development: Medicaid-covered births in Wisconsin, 2010-2019.

Prenatal opioid exposure is an established public health problem, in particular among Medicaid-covered births. Yet, existing prevalence rates are plausibly underestimated. We leverage extensive linked longitudinal administrative data for all Medicaid-covered live births in Wisconsin from 2010 to 2019 to estimate a range of prevalence rates using an innovative strategy that jointly accounts for both likelihood of exposure and potential risk to prenatal development. We find that 20.8% of infants may have been prenatally exposed to opioids, with 1.7% diagnosed with neonatal abstinence syndrome and an additional 1.2% having a high combined likelihood of exposure and potential risk to prenatal development, 2.6% a moderate combined likelihood and risk, and 15.3% a low or uncertain combined likelihood and risk. We assess improvements in prevalence estimates based on our nuanced classification relative to those of prior studies. Our strategy could be broadly used to quantify the scope of the opioid crisis for pregnant populations, target interventions, and promote child health and development.

How do we understand the value of drug checking as a component of harm reduction services? A qualitative exploration of client and provider perspectives.

BACKGROUND: Mortality related to opioid overdose in the U.S. has risen sharply in the past decade. In California, opioid overdose death rates more than tripled from 2018 to 2021, and deaths from synthetic opioids such as fentanyl increased more than seven times in those three years alone. Heightened attention to this crisis has attracted funding and programming opportunities for prevention and harm reduction interventions. Drug checking services offer people who use drugs the opportunity to test the chemical content of their own supply, but are not widely used in North America. We report on qualitative data from providers and clients of harm reduction and drug checking services, to explore how these services are used, experienced, and considered. METHODS: We conducted in-depth semi-structured key informant interviews across two samples of drug checking stakeholders: "clients" (individuals who use drugs and receive harm reduction services) and "providers" (subject matter experts and those providing clinical and harm reduction services to people who use drugs). Provider interviews were conducted via Zoom from June-November, 2022. Client interviews were conducted in person in San Francisco over a one-week period in November 2022. Data were analyzed following the tenets of thematic analysis. RESULTS: We found that the value of drug checking includes but extends well beyond overdose prevention. Participants discussed ways that drug checking can fill a regulatory vacuum, serve as a tool of informal market regulation at the community level, and empower public health surveillance systems and clinical response. We present our findings within three key themes: (1) the role of drug checking in overdose prevention; (2) benefits to the overall agency, health, and wellbeing of people who use drugs; and (3) impacts of drug checking services at the community and systems levels. CONCLUSION: This study contributes to growing evidence of the effectiveness of drug checking services in mitigating risks associated with substance use, including overdose, through enabling people who use and sell drugs to test their own supply. It further contributes to discussions around the utility of drug checking and harm reduction, in order to inform legislation and funding allocation.

Licensure Policies May Help States Ensure Access To Opioid Use Disorder Medication In Specialty Addiction Treatment.

Despite the devastating toll of the overdose crisis in the United States, many addiction treatment programs do not offer medications for opioid use disorder (MOUD). Several states have incorporated MOUD requirements into their standards for treatment program licensure. This study examined policy officials' and treatment providers' perspectives on the implementation of these policies. During 2020-22, we conducted thirty-one semistructured interviews with forty policy officials and treatment providers in nine states identified through a legal analysis. Of these states, three states required treatment organizations to offer MOUD, and two prohibited organizations from denying admission to people receiving MOUD. Qualitative findings revealed that licensure policies were part of a broader effort to transition the specialty treatment system to a model of care more consistent with medical evidence; states perceived tension between raising quality standards and maintaining adequate treatment capacity; aligning other state policies with MOUD access goals facilitated implementation of the licensure requirement; and measuring compliance was challenging. Licensure may offer states an opportunity to take a more active role in ensuring access to effective treatment.

Exploring dual diagnosis in opioid agonist treatment patients: a registry-linkage study in Czechia and Norway.

BACKGROUND: Knowledge of co-occurring mental disorders (termed 'dual diagnosis') among patients receiving opioid agonist treatment (OAT) is scarce. This study aimed (1) to estimate the prevalence and structure of dual diagnoses in two national cohorts of OAT patients and (2) to compare mental disorders between OAT patients and the general populations stratified on sex and standardized by age. METHODS: A registry-linkage study of OAT patients from Czechia (N = 4,280) and Norway (N = 11,389) during 2010-2019 was conducted. Data on mental disorders (F00-F99; ICD-10) recorded in nationwide health registers were linked to the individuals registered in OAT. Dual diagnoses were defined as any mental disorder excluding substance use disorders (SUDs, F10-F19; ICD-10). Sex-specific age-standardized morbidity ratios (SMR) were calculated for 2019 to compare OAT patients and the general populations. RESULTS: The prevalence of dual diagnosis was 57.3% for Czechia and 78.3% for Norway. In Czechia, anxiety (31.1%) and personality disorders (25.7%) were the most prevalent, whereas anxiety (33.8%) and depression (20.8%) were the most prevalent in Norway. Large country-specific variations were observed, e.g., in ADHD (0.5% in Czechia, 15.8% in Norway), implying differences in screening and diagnostic practices. The SMR estimates for any mental disorders were 3.1 (females) and 5.1 (males) in Czechia and 5.6 (females) and 8.2 (males) in Norway. OAT females had a significantly higher prevalence of co-occurring mental disorders, whereas SMRs were higher in OAT males. In addition to opioid use disorder (OUD), other substance use disorders (SUDs) were frequently recorded in both countries. CONCLUSIONS: Results indicate an excess of mental health problems in OAT patients compared to the general population of the same sex and age in both countries, requiring appropriate clinical attention. Country-specific differences may stem from variations in diagnostics and care, reporting to registers, OAT provision, or substance use patterns.

Associations Between a Primary Care-Delivered Alcohol-Related Brief Intervention and Subsequent Opioid-Related Outcomes.

OBJECTIVE: The co-occurrence of unhealthy alcohol use and opioid misuse is high and associated with increased rates of overdose, emergency health care utilization, and death. The current study examined whether receipt of an alcohol-related brief intervention is associated with reduced risk of negative downstream opioid-related outcomes. METHODS: This retrospective cohort study included all VISN-6 Veterans Affairs (VA) patients with Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) screening results (N=492,748) from 2014 to 2019. Logistic regression was used to examine the association between documentation of an alcohol-related brief intervention and probability of a new 1) opioid prescription, 2) opioid use disorder (OUD) diagnosis, or 3) opioid-related hospitalization in the following year, controlling for demographic and clinical covariates. RESULTS: Of the veterans, 13% (N=63,804) had "positive" AUDIT-C screen results. Of those, 72% (N=46,216) had a documented alcohol-related brief intervention. Within 1 year, 8.5% (N=5,430) had a new opioid prescription, 1.1% (N=698) had a new OUD diagnosis, and 0.8% (N=499) had a new opioid-related hospitalization. In adjusted models, veterans with positive AUDIT-C screen results who did not receive an alcohol-related brief intervention had higher odds of new opioid prescriptions (adjusted odds ratio [OR]=1.10, 95% CI=1.03-1.17) and new OUD diagnoses (adjusted OR=1.19, 95% CI=1.02-1.40), while new opioid-related hospitalizations (adjusted OR=1.19, 95% CI=0.99-1.44) were higher although not statistically significant. Removal of medications for OUD (MOUD) did not impact associations. All outcomes were significantly associated with an alcohol-related brief intervention in unadjusted models. CONCLUSIONS: The VA's standard alcohol-related brief intervention is associated with subsequent lower odds of a new opioid prescription or a new OUD diagnosis. Results suggest a reduction in a cascade of new opioid-related outcomes from prescriptions through hospitalizations.

A qualitative study of experiences with physical activity among people receiving opioid agonist therapy.

BACKGROUND: Physical or mental health comorbidities are common among people with substance use disorders undergoing opioid agonist therapy. As both a preventive and treatment strategy, exercise offers various health benefits for several conditions. Exercise interventions to people with substance use disorders receiving opioid agonist therapy are limited. This study aims to explore experiences with physical activity, perceived barriers, and facilitators among people receiving opioid agonist therapy. METHOD: Fourteen qualitative interviews were conducted with individuals receiving opioid agonist therapy in outpatient clinics in Western Norway. RESULTS: Most were males in the age range 30 to 60 years. Participants had diverse and long-term substance use histories, and most received buprenorphine-based opioid agonist therapy. The identified themes were (1) Physical limitations: Participants experienced health-related problems like breathing difficulties, pain, and reduced physical function. (2) Social dynamics: Social support was essential for participating in physical activities and many argued for group exercises, but some were concerned about the possibility of meeting persons influenced by substances in a group setting, fearing temptations to use substances. (3) Shift in focus: As participants felt the weight of the health burden, their preference for activities shifted from sports aiming for "adrenaline" to a health promoting focus. (4) COVID-19's impact on exercise: because of the pandemic, group activities were suspended, and participants described it as challenging to resume. (5) Implementation preferences in clinics: Not interfering with opioid medication routines was reported to be essential. CONCLUSION: This study offers valuable insights for the development of customized exercise interventions aimed at enhancing the health and well-being of patients undergoing opioid agonist therapy. These findings underscore the significance of addressing social dynamics, overcoming physical limitations, and implementing a practical and effective exercise regimen.

Matching study design to prescribing intention: The prevalent new-user design for studying abuse-deterrent formulations of opioids.

PURPOSE: In drug studies, research designs requiring no prior exposure to certain drug classes may restrict important populations. Since abuse-deterrent formulations (ADF) of opioids are routinely prescribed after other opioids, choice of study design, identification of appropriate comparators, and addressing confounding by "indication" are important considerations in ADF post-marketing studies. METHODS: In a retrospective cohort study using claims data (2006-2018) from a North Carolina private insurer [NC claims] and Merative MarketScan [MarketScan], we identified patients (18-64 years old) initiating ADF or non-ADF extended-release/long-acting (ER/LA) opioids. We compared patient characteristics and described opioid treatment history between treatment groups, classifying patients as traditional (no opioid claims during prior six-month washout period) or prevalent new users. RESULTS: We identified 8415 (NC claims) and 147 978 (MarketScan) ADF, and 10 114 (NC claims) and 232 028 (MarketScan) non-ADF ER/LA opioid initiators. Most had prior opioid exposure (ranging 64%-74%), and key clinical differences included higher prevalence of recent acute or chronic pain and surgery among patients initiating ADFs compared to non-ADF ER/LA initiators. Concurrent immediate-release opioid prescriptions at initiation were more common in prevalent new users than traditional new users. CONCLUSIONS: Careful consideration of the study design, comparator choice, and confounding by "indication" is crucial when examining ADF opioid use-related outcomes.

Neonatal Abstinence Syndrome/Neonatal Opioid Withdrawal Syndrome: An Ecological View of Non-Pharmacologic Interventions for Feeding Success.

The number of infants diagnosed with neonatal abstinence syndrome (NAS) or neonatal opioid withdrawal syndrome (NOWS) has increased. The expression of NAS/NOWS symptoms differs and typically begins within the first few days of life, considered a critical period for feeding skill establishment, nourishment, and attachment. Non-pharmacologic interventions may be deployed to reduce or eliminate the need for replacement opioids while targeting outcomes like feeding dysfunction. Critical care providers can benefit from a structured examination of disordered feeding experiences to inform their selection of non-pharmacologic interventions. This structure can be provided using the Ecology of Human Performance model.

An acute phase reaction from zoledronate mimicking symptoms seen in opioid withdrawal: a case report.

BACKGROUND: Zoledronate, a bisphosphonate, is a potent first-line treatment for osteoporosis. It is also a preferred treatment for hypercalcemia especially when unresponsive to intravenous fluids. Bisphosphonates can cause acute phase reactions that mimic opioid withdrawal symptoms, which can confound provider decision-making. Our case highlights cognitive bias involving a patient with opioid use disorder who received zoledronate for hypercalcemia secondary to immobilization and significant bone infection. CASE PRESENTATION: A 41-year-old male is admitted with a past medical history of active intravenous opioid use complicated by group A streptococcal bacteremia with L5-S1 discitis and osteomyelitis, L2-L3 osteomyelitis, and left ankle abscess/septic arthritis status post left ankle washout. His pain was well-controlled by acute pain service with ketamine infusion (discontinued earlier), opioids, acetaminophen, buprenorphine-naloxone, cyclobenzaprine, gabapentin, and naproxen. Intravenous opioids were discontinued, slightly decreasing the opioid regimen. A day later, the patient reported tachycardia, diaphoresis, myalgias, and chills, which the primary team reconsulted acute pain service for opioid withdrawal. However, the patient received a zoledronate infusion for hypercalcemia, on the same day intravenous opioids were discontinued. He had no other medications known to cause withdrawal-like symptoms per chart review. Therefore, it was suspected that an acute phase reaction occurred, commonly seen within a few days of bisphosphonate use. CONCLUSION: Zoledronate, well known for causing acute phase reactions, was likely the cause of withdrawal-like symptoms. Acute phase reactions with bisphosphonates mostly occur in the first infusion, and the incidence decreases with subsequent infusions. Symptoms typically occur 24-72 h post-infusion, and last at most for 72 h. Cognitive bias led the primary team to be concerned with opioid withdrawal rather than investigating other causes for the patient's presentation. Therefore, providers should thoroughly investigate potential etiologies and rule them out accordingly to provide the best care. Health care providers should also be aware of the implicit biases that potentially impact the quality of care they provide to patients.

A substance use disorder training curriculum for internal medicine residents using resident-empaneled patients.

BACKGROUND: Internal Medicine (IM) residents frequently encounter, but feel unprepared to diagnose and treat, patients with substance use disorders (SUD). This is compounded by negative regard for patients with SUD. Optimal education strategies are needed to empower IM residents to care for patients with SUD. The objective of this study was to evaluate a brief SUD curriculum for IM residents, using resident-empaneled patients as an engaging educational strategy. METHODS: Following a needs assessment, a 2-part SUD curriculum was developed for IM residents at the University of Chicago during the 2018-2019 academic year as part of the ambulatory curriculum. During sessions on Opioid Use Disorder (OUD) and Alcohol Use Disorder (AUD), a facilitator covered concepts about screening, diagnosis, and treatment. In session, residents completed structured worksheets applying concepts to one of their primary care patients. A post-session assessment included questions on knowledge, preparedness & attitudes. RESULTS: Resident needs assessment (n = 44/105, 42% response rate) showed 86% characterized instruction received during residency in SUD as none or too little, and residents did not feel prepared to treat SUD. Following the AUD session, all residents (n = 22) felt prepared to diagnose and treat AUD. After the OUD session, all residents (n = 19) felt prepared to diagnose, and 79% (n = 15) felt prepared to treat OUD. Residents planned to screen for SUD more or differently, initiate harm reduction strategies and increase consideration of pharmacotherapy. CONCLUSIONS: A brief curricular intervention for AUD and OUD using resident-empaneled patients can empower residents to integrate SUD diagnosis and management into practice.

Growing together: Optimization of care through quality improvement for the mother/infant dyad affected by perinatal opioid use.

The care of the dyad affected by opioid use disorder (OUD) requires a multi-disciplinary approach that can be challenging for institutions to develop and maintain. However, over the years, many institutions have developed quality improvement (QI) initiatives aimed at improving outcomes for the mother, baby, and family. Over time, QI efforts targeting OUD in the perinatal period have evolved from focusing separately on the mother and baby to efforts addressing care of the dyad and family during pregnancy, delivery, and postpartum. Here, we review recent and impactful QI initiatives that serve as examples of work improving outcomes for this population. Further, we advocate that this work be done through a racial equity lens, given ongoing inequities in the care of particularly non-white populations with substance use disorders. Through QI frameworks, even small interventions can result in meaningful changes to the care of babies and families and improved outcomes.

Foster Care and Health in Medicaid-Enrolled Children Experiencing Parental Opioid Use Disorder.

Importance: The burden of the US opioid crisis has fallen heavily on children, a vulnerable population increasingly exposed to parental opioid use disorder (POUD) in utero or during childhood. A paucity of studies have investigated foster care involvement among those experiencing parental opioid use during childhood and the associated health and health care outcomes. Objective: To examine the health and health care outcomes of children experiencing POUD with and without foster care involvement. Design, Setting, and Participants: This population-based cohort study used nationwide Medicaid claims data from January 1, 2014, to December 31, 2020. Participants included Medicaid-enrolled children experiencing parental opioid use-related disorder during ages 4 to 18 years. Data were analyzed between January 2023 and February 2024. Exposure: Person-years with (exposed) and without (nonexposed) foster care involvement, identified using Medicaid eligibility, procedure, and diagnostic codes. Main Outcomes and Measures: The main outcomes included physical and mental health conditions, developmental disorders, substance use, and health care utilization. The Pearson χ2 test, the t test, and linear regression were used to compare outcomes in person-years with (exposed) and without (nonexposed) foster care involvement. An event study design was used to examine health care utilization patterns before and after foster care involvement. Results: In a longitudinal sample of 8 939 666 person-years from 1 985 180 Medicaid-enrolled children, 49% of children were females and 51% were males. Their mean (SD) age was 10 (4.2) years. The prevalence of foster care involvement was 3% (276 456 person-years), increasing from 1.5% in 2014 to 4.7% in 2020. Compared with those without foster care involvement (8 663 210 person-years), foster care involvement was associated with a higher prevalence of developmental delays (12% vs 7%), depression (10% vs 4%), trauma and stress (35% vs 7%), and substance use-related disorders (4% vs 1%; P < .001 for all). Foster children had higher rates of health care utilization across a wide array of preventive services, including well-child visits (64% vs 44%) and immunizations (41% vs 31%; P < .001 for all). Health care utilization increased sharply in the first year entering foster care but decreased as children exited care. Conclusions and Relevance: In this cohort study of Medicaid-enrolled children experiencing parental opioid use-related disorder, foster care involvement increased significantly between 2014 and 2020. Involvement was associated with increased rates of adverse health outcomes and health care utilization. These findings underscore the importance of policies that support children and families affected by opioid use disorder, as well as the systems that serve them.

Rapid Initiation of Injection Naltrexone for Opioid Use Disorder: A Stepped-Wedge Cluster Randomized Clinical Trial.

Importance: Injectable extended-release (XR)-naltrexone is an effective treatment option for opioid use disorder (OUD), but the need to withdraw patients from opioid treatment prior to initiation is a barrier to implementation. Objective: To compare the effectiveness of the standard procedure (SP) with the rapid procedure (RP) for XR-naltrexone initiation. Design, Setting, and Participants: The Surmounting Withdrawal to Initiate Fast Treatment with Naltrexone study was an optimized stepped-wedge cluster randomized trial conducted at 6 community-based inpatient addiction treatment units. Units using the SP were randomly assigned at 14-week intervals to implement the RP. Participants admitted with OUD received the procedure the unit was delivering at the time of their admission. Participant recruitment took place between March 16, 2021, and July 18, 2022. The last visit was September 21, 2022. Interventions: Standard procedure, based on the XR-naltrexone package insert (approximately 5-day buprenorphine taper followed by a 7- to 10-day opioid-free period and RP, defined as 1 day of buprenorphine at minimum necessary dose, 1 opioid-free day, and ascending low doses of oral naltrexone and adjunctive medications (eg, clonidine, clonazepam, antiemetics) for opioid withdrawal. Main Outcomes and Measures: Receipt of XR-naltrexone injection prior to inpatient discharge (primary outcome). Secondary outcomes included opioid withdrawal scores and targeted safety events and serious adverse events. All analyses were intention-to-treat. Results: A total of 415 participants with OUD were enrolled (mean [SD] age, 33.6 [8.48] years; 205 [49.4%] identified sex as male); 54 [13.0%] individuals identified as Black, 91 [21.9%] as Hispanic, 290 [69.9%] as White, and 22 [5.3%] as multiracial. Rates of successful initiation of XR-naltrexone among the RP group (141 of 225 [62.7%]) were noninferior to those of the SP group (68 of 190 [35.8%]) (odds ratio [OR], 3.60; 95% CI, 2.12-6.10). Withdrawal did not differ significantly between conditions (proportion of days with a moderate or greater maximum Clinical Opiate Withdrawal Scale score (>12) for RP vs SP: OR, 1.25; 95% CI, 0.62-2.50). Targeted safety events (RP: 12 [5.3%]; SP: 4 [2.1%]) and serious adverse events (RP: 15 [6.7%]; SP: 3 [1.6%]) were infrequent but occurred more often with RP than SP. Conclusions and Relevance: In this trial, the RP of XR-naltrexone initiation was noninferior to the standard approach and saved time, although it required more intensive medical management and safety monitoring. The results of this trial suggest that rapid initiation could make XR-naltrexone a more viable treatment for patients with OUD. Trial Registration: ClinicalTrials.gov Identifier: NCT04762537.

Vaccines as Immunotherapies for Substance Use Disorders.

Substance use disorders (SUD) present a worldwide challenge with few effective therapies except for the relative efficacy of opioid pharmacotherapies, despite limited treatment access. However, the proliferation of illicit fentanyl use initiated a dramatic and cascading epidemic of lethal overdoses. This rise in fentanyl overdoses regenerated an interest in vaccine immunotherapy, which, despite an optimistic start in animal models over the past 50 years, yielded disappointing results in human clinical trials of vaccines against nicotine, stimulants (cocaine and methamphetamine), and opioids. After a brief review of clinical and selected preclinical vaccine studies, the "lessons learned" from the previous vaccine clinical trials are summarized, and then the newest challenge of a vaccine against fentanyl and its analogs is explored. Animal studies have made significant advances in vaccine technology for SUD treatment over the past 50 years, and the resulting anti-fentanyl vaccines show remarkable promise for ending this epidemic of fentanyl deaths.

Harm Reduction for Opioid Use Disorder: Strategies and Outcome Metrics.

Tweet: The authors discuss harm reduction strategies and associated outcome metrics in relation to the ongoing opioid crisis.

Using decision tree models and comprehensive statewide data to predict opioid overdoses following prison release.

PURPOSE: Identifying predictors of opioid overdose following release from prison is critical for opioid overdose prevention. METHODS: We leveraged an individually linked, state-wide database from 2015-2020 to predict the risk of opioid overdose within 90 days of release from Massachusetts state prisons. We developed two decision tree modeling schemes: a model fit on all individuals with a single weight for those that experienced an opioid overdose and models stratified by race/ethnicity. We compared the performance of each model using several performance measures and identified factors that were most predictive of opioid overdose within racial/ethnic groups and across models. RESULTS: We found that out of 44,246 prison releases in Massachusetts between 2015-2020, 2237 (5.1%) resulted in opioid overdose in the 90 days following release. The performance of the two predictive models varied. The single weight model had high sensitivity (79%) and low specificity (56%) for predicting opioid overdose and was more sensitive for White non-Hispanic individuals (sensitivity = 84%) than for racial/ethnic minority individuals. CONCLUSIONS: Stratified models had better balanced performance metrics for both White non-Hispanic and racial/ethnic minority groups and identified different predictors of overdose between racial/ethnic groups. Across racial/ethnic groups and models, involuntary commitment (involuntary treatment for alcohol/substance use disorder) was an important predictor of opioid overdose.