Predictors of engagement in screening for a hepatitis C virus (HCV) treatment trial in a rural Appalachian community.

An HCV treatment trial was initiated in September 2019 to address the opioid/hepatitis C virus (HCV) syndemic in rural Kentucky. The focus of the current analysis is on participation in diagnostic screening for the trial. Initial eligibility (≥18 years of age, county resident) was established by phone followed by in-person HCV viremia testing. 900 rural residents met the inclusion criteria and comprised the analytic sample. Generalized linear models were specified to estimate the relative risk of non-attendance at the in-person visit determining HCV eligibility. Approximately one-quarter (22.1%) of scheduled participants were no-shows. People who inject drugs were no more likely than people not injecting drugs to be a no-show; however, participants ≤35 years of age were significantly less likely to attend. While the median time between phone screening and scheduled in-person screening was only 2 days, each additional day increased the odds of no-show by 3% (95% confidence interval: 2%-3%). Finally, unknown HCV status predicted no-show even after adjustment for age, gender, days between screenings and injection status. We found that drug injection did not predict no-show, further justifying expanded access to HCV treatment among people who inject drugs. Those 35 years and younger were more likely to no-show, suggesting that younger individuals may require targeted strategies for increasing testing and treatment uptake. Finally, streamlining the treatment cascade may also improve outcomes, as participants in the current study were more likely to attend if there were fewer days between phone screening and scheduled in-person screening.

Dissonance in the face of Alzheimer's disease breakthroughs: clinician and lay stakeholder acceptance, concerns and willingness to pay for emerging disease-modifying therapies.

BACKGROUND: Introducing new disease-modifying therapies (DMTs) for Alzheimer's disease demands a fundamental shift in diagnosis and care for most health systems around the world. Understanding the views of health professionals, potential patients, care partners and taxpayers is crucial for service planning and expectation management about these new therapies. AIMS: To investigate the public's and professionals' perspectives regarding (1) acceptability of new DMTs for Alzheimer's disease; (2) perceptions of risk/benefits; (3) the public's willingness to pay (WTP). METHOD: Informed by the 'theoretical framework of acceptability', we conducted two online surveys with 1000 members of the general public and 77 health professionals in Ireland. Descriptive and multivariate regression analyses examined factors associated with DMT acceptance and WTP. RESULTS: Healthcare professionals had a higher acceptance (65%) than the general public (48%). Professionals were more concerned about potential brain bleeds (70%) and efficacy (68%), while the public focused on accessibility and costs. Younger participants (18-24 years) displayed a higher WTP. Education and insurance affected WTP decisions. CONCLUSIONS: This study exposes complex attitudes toward emerging DMTs for Alzheimer's disease, challenging conventional wisdom in multiple dimensions. A surprising 25% of the public expressed aversion to these new treatments, despite society's deep-rooted fear of dementia in older age. Healthcare professionals displayed nuanced concerns, prioritising clinical effectiveness and potential brain complications. Intriguingly, younger, better-educated and privately insured individuals exhibited a greater WTP, foregrounding critical questions about healthcare equity. These multifaceted findings serve as a guidepost for healthcare strategists, policymakers and ethicists as we edge closer to integrating DMTs into Alzheimer's disease care.

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.

Alternatives to dental opioid prescribing after tooth extraction (ADOPT): protocol for a stepped wedge cluster randomized trial.

BACKGROUND: Dentists and oral surgeons are leading prescribers of opioids to adolescents and young adults (AYA), who are at high risk for developing problematic opioid use after an initial exposure. Most opioids are prescribed after tooth extraction, but non-opioid analgesics provide similar analgesia and are recommended by multiple professional organizations. METHODS: This multi-site stepped wedge cluster-randomized trial will assess whether a multicomponent behavioral intervention can influence opioid prescribing behavior among dentists and oral surgeons compared to usual practice. Across up to 12 clinical practices (clusters), up to 33 dentists/oral surgeons (provider participants) who perform tooth extractions for individuals 12-25 years old will be enrolled. After enrollment, all provider participants will receive the intervention at a time based on the sequence to which their cluster is randomized. The intervention consists of prescriber education via academic detailing plus provision of standardized patient post-extraction instructions and blister packs of acetaminophen and ibuprofen. Provider participants will dispense the blister packs and distribute the patient instructions at their discretion to AYA undergoing tooth extraction, with or without additional analgesics. The primary outcome is a binary, patient-level indicator of electronic post-extraction opioid prescription. Data for the primary outcome will be collected from the provider participant's electronic health records quarterly throughout the study. Provider participants will complete a survey before and approximately 3 months after transitioning into the intervention condition to assess implementation outcomes. AYA patients undergoing tooth extraction will be offered a survey to assess pain control and satisfaction with pain management in the week after their extraction. Primary analyses will use generalized estimating equations to compare the binary patient-level indicator of being prescribed a post-extraction opioid in the intervention condition compared to usual practice. Secondary analyses will assess provider participants' perceptions of feasibility and appropriateness of the intervention, and patient-reported pain control and satisfaction with pain management. Analyses will adjust for patient-level factors (e.g., sex, number of teeth extracted, etc.). DISCUSSION: This real-world study will address an important need, providing information on the effectiveness of a multicomponent intervention at modifying dental prescribing behavior and reducing opioid prescriptions to AYA. CLINICALTRIALS: GOV: NCT06275191.

Cannabinoid Poisoning-Related Emergency Department Visits and Inpatient Hospitalizations in Kentucky, 2017 to 2019.

Background and objectives: Cannabis is the most used federally illicit substance. Due to widespread medicinal use and state-level legalization, public perceptions of cannabis have shifted toward the assumption that cannabis is safe. However, cannabinoids can cause adverse medical complications that may lead people to seek treatment. This study characterized cannabinoid poisoning-related medical encounters, poisoning involving cannabinoids and other psychoactive substances, and cannabinoid poisoning-related cardiac complications. Methods: Administrative billing data for emergency department visits and inpatient hospitalizations in acute care facilities with a discharge date from January 1, 2017 to December 31, 2019 were used to characterize cannabinoid poisoning events in Kentucky, identified by ICD-10-CM diagnosis code T40.7X. Results: There were 1,490 encounters of cannabinoid poisoning; patients were primarily non-Hispanic White males, ages 15-44, who had Medicaid and lived in a metropolitan area. Of those, 31.21% involved poisoning with a second psychoactive substance, primarily stimulants and/or opioids, and 17.72% experienced a cardiac complication. Cannabinoid-polydrug poisoning was associated with inpatient treatment (χ2=199.18, p < 0.001) and cardiac complications (χ2=4.58, p < 0.001). Discussion and Conclusions: These results are consistent with other state-level data. Patients who were diagnosed with cannabis-polydrug poisoning, compared to cannabis alone poisoning, had greater odds of hospital admission and cardiac complications, and longer length of hospital stays. Scientific Significance: The health risks of cannabinoid use must be more broadly recognized, while timely and accurate data need to be shared to guide policies on cannabis access. Future research on cannabinoid poisoning should consider the involvement of other psychoactive drugs.

Palliative care interventions in advanced dementia.

BACKGROUND: Dementia is a chronic, progressive and ultimately fatal neurodegenerative disease. Advanced dementia is characterised by profound cognitive impairment, inability to communicate verbally and complete functional dependence. Usual care of people with advanced dementia is not underpinned universally by a palliative approach. Palliative care has focused traditionally on care of people with cancer, but for more than a decade, there have been calls worldwide to extend palliative care services to include all people with life-limiting illnesses in need of specialist care, including people with dementia. This review is an updated version of a review first published in 2016. OBJECTIVES: To assess the effect of palliative care interventions in advanced dementia. SEARCH METHODS: We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's Specialised Register on 7 October 2020. ALOIS contains records of clinical trials identified from monthly searches of several major healthcare databases, trial registries and grey literature sources. We ran additional searches across MEDLINE (OvidSP), Embase (OvidSP), four other databases and two trial registries on 7 October 2020 to ensure that the searches were as comprehensive and as up-to-date as possible. SELECTION CRITERIA: We searched for randomised (RCTs) and non-randomised controlled trials (nRCTs), controlled before-and-after studies and interrupted time series studies evaluating the impact of palliative care interventions for adults with advanced dementia of any type. Participants could be people with advanced dementia, their family members, clinicians or paid care staff. We included clinical interventions and non-clinical interventions. Comparators were usual care or another palliative care intervention. We did not exclude studies based on outcomes measured. DATA COLLECTION AND ANALYSIS: At least two review authors (SW, EM, PC) independently assessed all potential studies identified in the search against the review inclusion criteria. Two authors independently extracted data from eligible studies. Where appropriate, we estimated pooled treatment effects in a fixed-effect meta-analysis. We assessed the risk of bias of included studies using the Cochrane Risk of Bias tool and the overall certainty of the evidence for each outcome using GRADE. MAIN RESULTS: Nine studies (2122 participants) met the review inclusion criteria. Two studies were individually-randomised RCTs, six were cluster-randomised RCTs and one was a controlled before-and-after study. We conducted two separate comparisons: organisation and delivery of care interventions versus usual care (six studies, 1162 participants) and advance care planning interventions versus usual care (three studies, 960 participants). Two studies were carried out in acute hospitals and seven in nursing homes or long-term care facilities. For both comparisons, we found the included studies to be sufficiently similar to conduct meta-analyses. Changes to the organisation and delivery of care for people with advanced dementia may increase comfort in dying (MD 1.49, 95% CI 0.34 to 2.64; 5 studies, 335 participants; very low certainty evidence). However, the evidence is very uncertain and unlikely to be clinically significant. These changes may also increase the likelihood of having a palliative care plan in place (RR 5.84, 95% CI 1.37 to 25.02; 1 study, 99 participants; I2 = 0%; very low certainty evidence), but again the evidence is very uncertain. Such interventions probably have little effect on the use of non-palliative interventions (RR 1.11, 95% CI 0.71 to 1.72; 2 studies, 292 participants; I2 = 0%; moderate certainty evidence). They may also have little or no effect on documentation of advance directives (RR 1.46, 95% CI 0.50 to 4.25; 2 studies, 112 participants; I2 = 52%; very low certainty evidence), or whether discussions take place about advance care planning (RR 1.08, 95% CI 1.00 to 1.18; 1 study, 193 participants; I2 = 0%; very low certainty evidence) and goals of care (RR 2.36, 95% CI 1.00 to 5.54; 1 study, 13 participants; I2 = 0%; low certainty evidence). No included studies assessed adverse effects. Advance care planning interventions for people with advanced dementia probably increase the documentation of advance directives (RR 1.23, 95% CI 1.07 to 1.41; 2 studies, 384; moderate certainty evidence) and the number of discussions about goals of care (RR 1.33, 95% CI 1.11 to 1.59; 2 studies, 384 participants; moderate certainty evidence). They may also slightly increase concordance with goals of care (RR 1.39, 95% CI 1.08 to 1.79; 1 study, 63 participants; low certainty evidence). On the other hand, they may have little or no effect on perceived symptom management (MD -1.80, 95% CI -6.49 to 2.89; 1 study, 67 participants; very low certainty evidence) or whether advance care planning discussions occur (RR 1.04, 95% CI 0.87 to 1.24; 1 study, 67 participants; low certainty evidence). AUTHORS' CONCLUSIONS: The evidence on palliative care interventions in advanced dementia is limited in quantity and certainty. When compared to usual care, changes to the organisation and delivery of care for people with advanced dementia may lead to improvements in comfort in dying, but the evidence for this was of very low certainty. Advance care planning interventions, compared to usual care, probably increase the documentation of advance directives and the occurrence of discussions about goals of care, and may also increase concordance with goals of care. We did not detect other effects. The uncertainty in the evidence across all outcomes in both comparisons is mainly driven by imprecision of effect estimates and risk of bias in the included studies.

Factors influencing the cost of care and admission to long-term care for people with dementia in Ireland.

OBJECTIVE: To explore the factors associated with the cost of care and admission to long-term care (LTC) for people with dementia living at home in Ireland. METHODS: Data on formal and informal resource use for people with dementia, and their LTC admission, were obtained from a national study of spousal dementia caregivers. Functional status was measured using the Bristol Activities of Daily Living Scale, while behavioural and psychiatric symptoms were evaluated using the Neuropsychiatric Inventory. Multivariable regression analysis was used to model costs and the predictors of LTC admission. RESULTS: Physical and cognitive symptoms were significantly associated with costs. Severely impaired functional ability was associated with a €2,308 increase in mean total 30-day monthly costs. Psychosis was associated with a €335 increase in primary and community 30-day monthly care costs. These factors also make it more likely that a person with dementia is admitted to LTC. Having an older caregiver also increases the risk of admission to LTC, while living in a rural area and having a female caregiver reduce the likelihood of admission. CONCLUSIONS: Dependency matters for the cost of care. Physical and cognitive symptoms, caregiver age and gender, and geographic location are significant predictors of admission to LTC.

Outpatient Parenteral Antimicrobial Therapy Plus Buprenorphine for Opioid Use Disorder and Severe Injection-related Infections.

In a pilot randomized trial in persons with opioid use disorder hospitalized with injection-related infections, an innovative care model combining outpatient parenteral antimicrobial therapy with buprenorphine treatment had similar clinical and drug use outcomes to usual care (inpatient intravenous antibiotic completion) and shortened hospital length of stay by 23.5 days. CLINICAL TRIALS REGISTRATION: NCT03048643.

Longitudinal trends in nonmedical prescription opioid use in a cohort of rural Appalachian people who use drugs.

Rural Appalachia remains an epicenter of the prescription opioid epidemic. In 2008, a cohort study was undertaken to examine longitudinal trends in nonmedical prescription opioid use (NMPOU). Eight waves of data (2008-2020) from the Social Networks among Appalachian People (SNAP) cohort were utilized for the current analysis. Only those who reported recent (past 6-month) NMPOU at baseline are included (n = 498, 99%). Mixed-effects logistic regression was used to model factors associated with NMPOU over time. Recent NMPOU declined significantly over the past decade (p < .001). However, 54.1% of participants still engaged in NMPOU at their most recent follow-up. Receipt of benefits for a physical or mental disability (adjusted odds ratio [aOR]: 3.11, 95% Confidence Interval [CI]: 1.98, 4.90) and self-described poor health status (aOR: 3.67, 95% CI: 1.61, 8.37) were both associated with NMPOU. All treatment modalities (methadone maintenance, residential, outpatient counseling) tested in the model, with the notable exception of detoxification, were associated with significantly lower odds of NMPOU. Although significant declines in prescription opioid misuse were observed in the cohort, more than half of all participants were engaged in NMPOU more than a decade after entering the study. Substance use disorder (SUD) treatment (excluding detoxification) was shown associated with reduced odds of continued NMPOU; therefore, increasing access to evidence-based treatments should be a priority in rural areas affected by the ongoing opioid epidemic.

A randomized, double-blind, placebo-controlled study of the kappa opioid receptor antagonist, CERC-501, in a human laboratory model of smoking behavior.

Preclinical data indicate that selective kappa opioid receptor antagonists reduce nicotine self-administration and withdrawal symptoms. The aim of the current study was to determine whether treatment with CERC-501, an orally available, potent, and selective kappa opioid receptor antagonist, could alleviate nicotine withdrawal and craving and mitigate mood alterations associated with nicotine withdrawal in humans. Healthy, adult cigarette smokers were enrolled into this randomized, multisite, double-blind, placebo-controlled, crossover study. Participants completed two 8-day treatment phases during which they received either CERC-501 (15 mg, p.o., once daily) or placebo. On the seventh day of each dosing phase, participants were admitted as inpatients for an 18-hour cigarette abstinence period followed by experimental testing. The primary outcome measures were (a) performance on the McKee Smoking Lapse test (ie, latency to smoke in exchange for money) and (b) number of cigarettes self-administered during a 60-minute ad lib smoking period. Other outcomes included measures of craving, mood, anxiety, nicotine withdrawal, and subjective effects of cigarette smoking. A total of 71 participants who smoked an average of approximately 23 cigarettes per day were enrolled, and 56 subjects completed the study. CERC-501 was well tolerated, but it did not significantly alter the latency to start smoking (CERC-501: 16.5 min vs placebo: 17.7 min) or the number of cigarettes smoked (CERC-501: 3.3 cigarettes vs placebo: 3.1 cigarettes). Compared with placebo, CERC-501 also did not affect cigarette craving, mood, anxiety, nicotine withdrawal, or subjective effects of smoking. These findings do not support a role for CERC-501 in the treatment of nicotine use disorder.

Deploying science to change hearts and minds: Responding to the opioid crisis.

The U.S. opioid epidemic, now in its third decade, continues to claim tens of thousands of lives each year. Despite strong scientific evidence to support the deployment of effective interventions from prevention to treatment, implementation and access to quality care continue to lag, in part, due to continued opioid prescribing, siloing of treatment services for those with opioid use disorder (OUD), public support for non-evidence-based practices, stigma, and discrimination. Primary prevention efforts should focus on avoiding exposure to opioids for chronic non-cancer pain, as there is little evidence of efficacy but substantial evidence of harms. FDA-approved medications for OUD (MOUD) have incontrovertible evidence supporting their efficacy, and their use saves lives. However, fewer than 10% of those in need are able to receive MOUD. The barriers include an inadequate workforce, inadequate reimbursement, challenges navigating the treatment system, and profiteering bad actors (e.g., treatment brokers, programs delivering non-evidenced-based care). Perhaps the greatest challenge (and deterrent from receiving MOUD) is stigma and lack of public knowledge about their efficacy. Detoxification is probably the most common form of "treatment" for OUD, but the evidence shows that detoxification actually increases the risk for overdose. Expansion of MOUD delivery in the criminal justice system, health care systems and communities is essential to stemming the tide of this epidemic. This article is a call to action for the scientific community to ensure that scientific evidence is guiding patient care, funding for treatment, and policy decisions that address the opioid epidemic.

Integrated outpatient treatment of opioid use disorder and injection-related infections: A description of a new care model.

Persons with opioid use disorder (OUD) hospitalized with severe, injection-related infections (SIRI) are frequently hospitalized for the duration of IV antibiotic treatment due to concerns regarding their eligibility for outpatient parenteral antimicrobial therapy (OPAT), which is the standard of care for prolonged IV antibiotic courses for patients without drug use. As part of a pilot study, a novel, integrated care model was developed where patients with OUD and SIRI receive addiction consultation and buprenorphine induction while hospitalized, followed by ongoing management in an outpatient clinic that combines office-based opioid treatment with buprenorphine pharmacotherapy and counseling services with OPAT. Through three illustrative case vignettes the outpatient model is described along with challenges, lessons learned and future directions.

Implementing Treatment of Opioid-Use Disorder in Rural Settings: a Focus on HIV and Hepatitis C Prevention and Treatment.

PURPOSE OF REVIEW: To describe the epidemiology of opioid-use disorder in the rural United States (U.S.) as it pertains to HIV and hepatitis C transmission and treatment resources. RECENT FINDINGS: Heroin and fentanyl analogs have surpassed prescription opioids in their availability in rural opioid markets adding to HIV and hepatitis C (HCV) and overdose risks. Only 18% of rural individuals live in towns with inpatient services which are of limited quality and utility. Opioid treatment programs that provide methadone are not located in rural areas and only 3% of the primary care providers have the ability to prescribe buprenorphine. National models and resources have been established but lack implementation in rural areas leading to ongoing HIV and HCV transmission and overdose. Addressing the adverse impact of opioids in the rural U.S. will require a concerted effort to implement effective treatments according to national standards.

A Pharmacokinetic Study Examining Acetazolamide as a Novel Adherence Marker for Clinical Trials.

RATIONALE: Accurate assessment of medication adherence is critical for determination of medication efficacy in clinical trials, but most current methods have significant limitations. This study tests a subtherapeutic (microdose) of acetazolamide as a medication ingestion marker because acetazolamide is rapidly absorbed and excreted without metabolism in urine and can be noninvasively sampled. METHODS: In a double-blind, placebo-controlled, residential study, 10 volunteers received 15 mg oral acetazolamide for 4 consecutive days. Acetazolamide pharmacokinetics were assessed on day 3, and its pharmacokinetic and pharmacodynamic interactions with a model medication (30 mg oxycodone) were examined on day 4. The rate of acetazolamide elimination into urine was followed for several days after dosing cessation. RESULTS: Erythrocyte sequestration (half-life = 50.2 ± 18.5 h, mean ± SD, n = 6), resulted in the acetazolamide microdose exhibiting a substantially longer plasma half-life (24.5 ± 5.6 hours, n = 10) than previously reported for therapeutic doses (3-6 hours). After cessation of dosing, the rate of urinary elimination decreased significantly (F3,23 = 247: P < 0.05, n = 6) in a predictable manner with low intersubject variability and a half-life of 16.1 ± 3.8 h (n = 10). For each of 4 consecutive mornings after dosing cessation, the rates of urinary acetazolamide elimination remained quantifiable.There was no overall effect of acetazolamide on the pharmacodynamics, Cmax, Tmax, or elimination half-life of the model medication tested. Acetazolamide may have modestly increased overall oxycodone exposure (20%, P < 0.05) compared with one of the 2 days when oxycodone was given alone, but there were no observed effects of acetazolamide on oxycodone pharmacodynamic responses. CONCLUSIONS: Coformulation of a once-daily trial medication with an acetazolamide microdose may allow estimation of the last time of medication consumption for up to 96 hours postdose. Inclusion of acetazolamide may therefore provide an inexpensive new method to improve estimates of medication adherence in clinical trials.

Pharmacodynamic effects of oral oxymorphone: abuse liability, analgesic profile and direct physiologic effects in humans.

Oxymorphone is a semisynthetic µ-opioid agonist, marketed as a prescription analgesic purported to be twice as potent as oxycodone for pain relief. Oral formulations of oxymorphone were reintroduced in the United States in 2006 and reports of abuse ensued; however, there are limited data available on its pharmacodynamic effects. The current study aimed to examine the direct physiologic effects, relative abuse liability, analgesic profile and overall pharmacodynamic potency of oxymorphone in comparison with identical doses of oxycodone. Healthy, non-dependent opioid abusers (n = 9) were enrolled in this within-subject, double-blind, placebo-controlled, 3-week inpatient study. Seven experimental sessions (6.5 hours) were conducted, during which an oral dose of immediate-release formulations of oxymorphone (10, 20 and 40 mg), oxycodone (10, 20 and 40 mg) or placebo was administered. An array of physiologic, abuse liability and experimental pain measures was collected. At identical doses, oxymorphone produced approximately twofold less potent effects on miosis, compared with oxycodone. Oxymorphone also produced lesser magnitude effects on measures of respiratory depression, two experimental pain models and observer-rated agonist effects. However, 40 mg of oxymorphone was similar to 40 mg of oxycodone on several abuse-related subjective ratings. Formal relative potency analyses were largely invalid because of the substantially greater effects of oxycodone. Overall, oxymorphone is less potent on most pharmacodynamic measures, although at higher doses, its abuse liability is similar to oxycodone. These data suggest that the published clinical equianalgesic estimates may not be consistent with the observed direct physiologic effects of opioids, results of experimental pain models or abuse liability measures, as assessed in the human laboratory.

Distribution of naloxone for overdose prevention to chronic pain patients.

In this commentary, we reflect on the growing opioid overdose epidemic and propose that chronic pain patients prescribed opioids are contributing to growing mortality rates. We advocate for expanding naloxone access and overdose prevention training, which has historically been directed when available to injection drug users, to chronic pain patients who may be at high risk for accidental opioid overdose.

Examination of naloxone dosing patterns for opioid overdose by emergency medical services in Kentucky during increased fentanyl use from 2018 to 2021.

BACKGROUND: Fatal overdoses involving fentanyl/fentanyl analogs (F/FA) have increased in the US, raising questions about naloxone doses for F/FA overdose reversal. Emergency medical services (EMS) data provide an opportunity to examine naloxone administration changes as fentanyl increases in the illicit opioid supply. METHODS: Administered naloxone intranasal-equivalent total dose (INTD) in milligrams (mg) was calculated for Kentucky EMS suspected opioid overdose (SOO) encounters (n=33,846), 2018-2021, and patterns of administration were examined. County-level F/FA availability was measured as 1) proportion of fatal drug overdoses involving F/FA, and 2) F/FA police seizures. Linear mixed models estimated changes in INTD in relation to local F/FA availability accounting for patient characteristics. RESULTS: From 2018-2021, SOOs increased by 44% (6853 to 9888) with an average INTD increase from 4.5mg to 4.7mg, with more than 99% of encounters resulting in successful reversal each year. For SOO encounters examined by outcome at the scene (i.e., non-fatal fatal vs fatal), average INTD for non-fatal were 4.6mg compared to 5.9mg for fatal overdoses. Mixed modeling found no significant relationship between INTD and the two measures for local F/FA availability. CONCLUSION: As F/FA-involved overdose risk increased, we observed a modest increase in INTD administered in SOO EMS encounters - just slightly higher than the 4mg standard dose. The lack of significant relationship between F/FA and naloxone dose suggests that naloxone utilization in SOO with EMS involvement remains effective for overdose reversal, and that EMS naloxone dosing patterns have not changed substantially.

Get It in Writing: How to Make Medications for Opioid Use Disorder Available During Incarceration.

In a case example from the Kentucky HEALing Communities Study, extensive resources were deployed to address structural barriers and facilitate the provision of medication for opioid use disorder (OUD) in an urban county jail. However, implementation was unsuccessful, and this case example emphasizes the importance of including evidence-based medication for OUD (MOUD) treatment in the scope of work of jails' contracted medical providers. The privatization of correctional health care services allows local governments with opioid abatement funds to incorporate requirements into medical provider contracts to screen all people entering jails for OUD and to offer MOUD at intake, throughout incarceration, and upon release to everyone for whom it is clinically indicated. We provide sample contractual language that can be added to requests for medical provider proposals to help drive the private correctional health care market toward integrating MOUD treatment into their standard of care. This approach also could expedite efforts to scale up broad MOUD access across U.S. jails through sharing of workflows and best practices among the small group of national correctional health care companies contracted with jails in states with broad mandates, such as Massachusetts. Clinical Trial Registration: NCT04111939.

Drug disposal deserts: An assessment of receptacle availability in Kentucky community pharmacies.

PURPOSE: The purpose of this study was to describe the county-level availability of drug disposal receptacles in Kentucky community pharmacies and show the relationship between installed receptacles and opioid analgesic (OA)/controlled substance dispensing rates, stratifying where possible by urban-rural classification. METHODS: Using 2020 data from the Kentucky All Schedule Prescription Electronic Reporting program and disposal receptacle data from the US Drug Enforcement Agency, county-level comparisons were made between number of receptacles and OA/controlled substance dispensing rates. Logistic and negative binomial regression models were used to assess for differences between rural/urban county designation and odds of ≥1 disposal receptacle and compare the rates of receptacles per dispensed OA dose in rural/urban counties. FINDINGS: While rural counties saw higher OA and controlled substance dispensing rates, the majority (55.6%) of disposal receptacles were in urban locations. The odds of having at least 1 receptacle were higher in urban counties (OR 2.60, 95% CI: 1.15, 5.92) compared to rural. The estimated rate of disposal receptacles per million dispensed OA doses was found to be 0.47 (95% CI: 0.36, 0.61) in urban counties compared to 0.32 (95% CI: 0.25, 0.42) in rural counties, with an estimated rate ratio of 1.45 (95% CI: 1.01, 2.10). CONCLUSIONS: A mismatch between the availability of county-level disposal receptacles in community pharmacies and the volume of dispensed OAs/controlled substances exists, resulting in fewer receptacles per dispensed OA in rural counties compared to urban counties. Future efforts are necessary to increase access to convenient disposal receptacles located in community pharmacies, particularly in rural communities.

Pharmacokinetic-pharmacodynamic analysis of drug liking blockade by buprenorphine subcutaneous depot (CAM2038) in participants with opioid use disorder.

Buprenorphine is used to treat opioid use disorder (OUD). Weekly and monthly subcutaneous long-acting buprenorphine injections (CAM2038) provide more stable buprenorphine plasma levels and reduce the treatment burden, misuse, and diversion associated with sublingual transmucosal buprenorphine formulations. To characterize the pharmacokinetic/pharmacodynamic (PK/PD) relationship, a maximum inhibition (Imax) model was developed relating CAM2038 buprenorphine plasma concentration to drug liking maximum effect (Emax) visual analog scale (VAS; bipolar) score after intramuscular hydromorphone administration. Data included time-matched observations of buprenorphine plasma concentration and drug liking Emax VAS score after hydromorphone 18 mg administration in 47 non-treatment-seeking adults with moderate to severe OUD in a phase 2 study. Analysis used non-|linear mixed-effects modeling (NONMEM®). The final Imax model adequately described the PK/PD relationship between buprenorphine plasma concentration and drug liking Emax VAS score. Simulations showed drug liking was effectively blocked at low buprenorphine plasma concentrations (0.4 ng/mL) where the upper 95% confidence interval of the drug liking Emax VAS score was below the pre-defined 11-point complete blockade threshold. The buprenorphine plasma concentration required to achieve 90% of the maximal effect (IC90) of drug liking was 0.675 ng/mL. Interindividual variability in responses to buprenorphine was observed; some participants experienced fluctuating responses, and a few did not achieve drug liking blockade even with higher buprenorphine plasma concentrations. This affirms the need to individualize treatment and titrate doses for optimal treatment outcomes. PK/PD models were also developed for desire to use VAS and Clinical Opiate Withdrawal Scale (COWS) scores, with results aligned to those for drug liking.