Scarce perinatal social support for women with OUD: Opportunities for doula services.

PROBLEM: Persons with opioid use disorder (OUD) often lack social support, which is associated with improved recovery outcomes. BACKGROUND: In the last two decades, the rate of opioid use disorder (OUD) among pregnant people has quadrupled. QUESTION: This study aimed to describe the prenatal and postpartum social support networks and needs of persons with OUD and assess perceived acceptability of community-based social supports such as doulas. METHODS: This mixed methods study utilized quantitative and qualitative data to understand social support structures and needs. Data was collected through surveys -demographics and social mapping; Adverse Childhood Experiences (ACE) tool; Connor Davidson Resilience 25-item (CDRS-25) scale- and a semi-structured interview. A total of 34 participants from a single urban opioid treatment program consented to participate. FINDINGS: Participants were on average 34.9 years old, White (64.7%), and unemployed (91.2%). Participants described small perinatal social support networks, which decreased in size from the prenatal to postpartum period. Only half (52.9%) reported adequate prenatal and postpartum social support. Doulas and peer recovery support specialists were perceived as valuable in perinatal health, social support, and recovery domains, with interest in doulas seen particularly amongst those with fewer reported supports. DISCUSSION: The scarcity of prenatal and postpartum social support among persons with OUD is critical to address, given the increased risk of relapse during the postpartum period which has implications for the maternal child dyad. CONCLUSION: Due to multiple disparities in prenatal and postpartum social support (small networks, inadequate support), doulas represent a trusted community-based support to be integrated into healthcare teams to address maternal morbidity/mortality associated with opioid use.

Inpatient initiation of long-acting injectable buprenorphine at a community hospital: A retrospective case series.

OBJECTIVES: Determine if long-acting injectable buprenorphine (LAIB) can be successfully and safely administered in the hospital with minimal sublingual buprenorphine lead-in and potentially improve follow-up engagement in care. METHODS: We performed a retrospective case series of 46 patients who received LAIB while hospitalized at a safety-net community hospital. We abstracted demographic information, details about substance use disorder treatment history, in-hospital buprenorphine initiation methods and follow-up data from inpatient and outpatient electronic medical records. RESULTS: In total, 46 hospitalized patients received LAIB during the study period. The majority of our patients were older Black adults with Medicaid who self-reported intranasal heroin use. A low-dose buprenorphine initiation protocol was used most commonly, either in sublingual or intravenous form, with only two cases of precipitated withdrawal occurring during the buprenorphine initiation process and no cases of precipitated withdrawal after the administration of LAIB. 87% (40) of the patients received LAIB after receiving either sublingual or IV buprenorphine for fewer than the recommended seven days. Of the 46 hospitalized patients who received LAIB, 23 (50%) attended a follow-up addiction medicine appointment within 30 days of discharge. CONCLUSIONS: Hospital administration of LAIB could play an important role in retention in care after hospital discharge.

Fentanyl-positive urine drug screens in the emergency department: Association with intentional opioid misuse and racial disparities.

Background: An increase in opioid-related overdoses, notably from potent synthetic opioids like fentanyl, prompted this consideration of characteristics of emergency department (ED) patients with evidence for illicit fentanyl use or exposure, the correlation with intentional opioid misuse, and subsequent ED management. Methods: A retrospective review was performed of patients presenting to an urban academic medical center ED with evidence for illicit fentanyl use, determined by positive urine drug screens (UDS), from 6/2021 through 11/2021. Participant demographics, comorbidities, ED chief complaint and disposition, and evidence of intentional opioid misuse were considered. Secondary outcomes included provision of buprenorphine/naloxone and/or naloxone kits at discharge, ED recidivism, and six-month mortality. Bivariate comparisons and logistic regression models were performed. Results: Among 409 unique patients, most were white and male with a mean age of 39.4. Approximately half presented with opioid-related complaints. Evidence of intentional opioid misuse was identified in 72.6 % of patients. Black patients had 79 % lower odds of intentional opioid misuse compared to white patients. Regarding ED management, 28.8 % were discharged with buprenorphine/naloxone and 14.0 % with a naloxone kit. Black patients had 63 % lower odds of receiving buprenorphine/naloxone compared to white patients after controlling for covariates. Nearly 6 % of the study population died within six months of the initial ED visit. Conclusion: This fentanyl-focused review describes patient characteristics which largely mirror the epidemiology of the current opioid epidemic; however, despite evidence of objective exposure, it also suggests that Black patients may be less likely to use fentanyl intentionally. It also highlights potential disparities related to ED-based opioid misuse patient management.

Eat, Sleep, Console model for neonatal opioid withdrawal syndrome: a meta-analysis.

Background: The rising incidence of drug abuse among pregnant women has rendered neonatal opioid withdrawal syndrome a significant global health concern. Methods: Databases including PubMed, Web of Science, the Cochrane Library, Embase, Elton B. Stephens. Company (EBSCO), China National Knowledge Infrastructure (CNKI), and Wanfang were searched for comparative studies of the Eat, Sleep, Console model vs. traditional assessment tools for neonatal opioid withdrawal syndrome. Two reviewers conducted literature searches, screened according to the inclusion criteria, extracted data, and independently verified accuracy. All meta-analyses were conducted using Review Manager Version 5.4. Results: In total, 18 studies involving 4,639 neonates were included in the meta-analysis. The Eat, Sleep, Console model demonstrated superior outcomes in assessing neonatal opioid withdrawal syndrome, significantly reducing the need for pharmacological treatment [risk ratio = 0.44, 95% confidence interval (CI) = 0.34-0.56, P < 0.001], decreasing the length of hospital stay [standard mean difference (SMD) = -2.10, 95% CI = -3.43 to -0.78, P = 0.002], and shortening the duration of opioid treatment (SMD = -1.33, 95% CI = -2.22 to -0.45, P = 0.003) compared to the Finnegan Neonatal Abstinence Scoring System. Conclusions: The Eat, Sleep, Console model is more effective than the Finnegan Neonatal Abstinence Scoring System in improving the assessment and management of neonatal opioid withdrawal syndrome.

Inpatient Growth in Infants Requiring Pharmacologic Treatment for Neonatal Opioid Withdrawal Syndrome.

Aim: To assess inpatient growth parameter trajectories and to identify the type of opioid exposure and treatment characteristics influencing growth parameters of infants admitted to the newborn intensive care unit (NICU) for pharmacological treatment of neonatal opioid withdrawal syndrome (NOWS). Methods: Charts of term infants with NOWS admitted to NICU from 2012 to 2019, who received pharmacologic treatment, were reviewed. Intake (volume: mL/kg/day; calorie: kcal/kg/day) and growth parameter trajectories (weight, head circumference, and length) were analyzed based on the type of prenatal opioid exposure (short-acting opioids (SAOs), long-acting opioids (LAOs), and polysubstance), pharmacologic treatment, and sex. Growth measurement patterns over time were compared between groups using longitudinal mixed-effects models. Results: One hundred nineteen infants were included in the study with median birth weight Z-score of -0.19 at birth and decreased to a median of -0.72 at discharge. Exposure to SAO was associated with an increase in Z-scores nearing discharge across all growth parameters (Z-score for weight p = 0.03). Polysubstance exposure was associated with a decrease in Z-scores for length and head circumference throughout hospitalization. Infants with adjunct clonidine treatment had an increase in Z-score for weight trends. Male infants had a decrease in Z-scores for weight (male -0.96, female -0.59, interaction p = 0.06) and length (male -1.17, female -0.57, interaction p = 0.003) at Day 28. Despite the difference in growth trajectories, intake in terms of amount (mL/kg/day) and calorie intake (kcal/kg/day) was similar based on prenatal exposure, treatment, and sex. Conclusion: Infants with NOWS requiring pharmacologic treatment have a decrease in Z-scores for weight, length, and head circumference at birth and at hospital discharge. Infants with prenatal polysubstance exposure were at particular risk for poorer inpatient growth relative to infants exposed to SAO and LAO, indicated by lower Z-scores for length and occipital frontal circumference (OFC).

[Efficacy of transdermal lidocaine 5% patches in postoperative analgesia following knee arthroscopy]. / Efectividad del parche transdérmico de lidocaína 5% en la analgesia postoperatoria después de la artroscopía de rodilla.

INTRODUCTION: knee arthroscopy is a common orthopedic procedure associated with postoperative pain, so optimizing pain management is essential for patient recovery and satisfaction. Lidocaine, a local anesthetic with well-established safety profiles, offers a potential alternative to traditional analgesic methods. Research regarding lidocaine patches has been conducted in several types of surgeries (laparoscopy, gynecological surgery, prostatectomy, etc.) showing promising results for some. This study investigates the effectiveness of transdermal lidocaine 5% patches as a novel approach to postoperative analgesia after knee arthroscopy. MATERIAL AND METHODS: a randomized, single-blind, placebo-controlled trial was conducted with participants undergoing knee arthroscopy. Patients were divided into two groups: one receiving transdermal lidocaine 5% patches and the other a placebo, both along traditional postoperative pain management, and using opioid only in cases with moderate-severe pain. Pain scores, opioid consumption, and patient-reported outcomes were assessed at various postoperative intervals. RESULTS: there was a significant reduction in pain scores and opioid consumption in the lidocaine patch group compared to the placebo group. CONCLUSIONS: transdermal lidocaine 5% patches emerge as a promising adjunct to postoperative pain management in knee arthroscopy patients. Their ease of application, minimal side effects, and opioid-sparing effects contribute to a multifaceted analgesic approach. This study underscores the potential of transdermal lidocaine patches in enhancing the overall postoperative experience for knee arthroscopy patients, advocating for their consideration in clinical practice.

INTRODUCCIÓN: la artroscopía de rodilla es un procedimiento ortopédico común asociado con dolor postoperatorio, por lo que optimizar el manejo del dolor es esencial para la recuperación y la satisfacción del paciente. La lidocaína, un anestésico local con perfiles de seguridad bien establecidos, ofrece una alternativa potencial a los métodos analgésicos tradicionales. Se ha llevado a cabo investigación sobre los parches de lidocaína en diversos tipos de cirugías (laparoscopía, cirugía ginecológica, prostatectomía, etcétera), mostrando resultados prometedores en algunos casos. MATERIAL Y MÉTODOS: se realizó un ensayo clínico aleatorizado, ciego simple y controlado con placebo que incluyó participantes sometidos a artroscopía de rodilla. Los pacientes fueron divididos en dos grupos: uno recibió parches transdérmicos de lidocaína al 5% y otro un placebo, ambos junto con el manejo tradicional del dolor postoperatorio y utilizando opioides sólo en casos de dolor moderado a severo. Se evaluaron las puntuaciones de dolor, el consumo de opioides y los resultados informados por los pacientes en varios intervalos postoperatorios. RESULTADOS: se registró una reducción significativa en las puntuaciones de dolor y el consumo de opioides en el grupo de parches de lidocaína en comparación con el grupo de placebo. CONCLUSIONES: los parches transdérmicos de lidocaína al 5% emergen como un complemento prometedor para el manejo del dolor postoperatorio en pacientes sometidos a artroscopía de rodilla. Su facilidad de aplicación, mínimos efectos secundarios y efectos ahorradores de opioides contribuyen a un enfoque analgésico multifacético. Este estudio destaca el potencial de los parches de lidocaína transdérmica para mejorar la experiencia postoperatoria general de los pacientes con artroscopía de rodilla, abogando por su consideración en la práctica clínica.

The effectiveness and outcomes of epidural analgesia in patients undergoing open liver resection: a propensity score matching analysis.

BACKGROUND: Open liver resection necessitates a substantial upper abdominal inverted-L incision, resulting in severe pain and compromising patient recovery. Despite the efficacy of epidural analgesia in providing adequate postoperative analgesia, the potential epidural-related adverse effects should be carefully considered. This study aims to compare the efficacy and safety of continuous epidural analgesia and intravenous analgesia in open liver resection. METHODS: A retrospective study was conducted, collecting data from patients who underwent open liver resection between 2007 and 2017. Propensity score matching was implemented to mitigate confounding variables, with patients being matched in a 1:1 ratio based on propensity scores. The primary outcome was the comparison of postoperative morphine consumption at 24, 48, and 72 hours between the two groups. Secondary outcomes included pain scores, postoperative outcomes, and epidural-related adverse effects. RESULTS: A total of 612 patients were included, and after matching, there were 204 patients in each group. Opioid consumption at 24, 48, and 72 hours postoperatively was statistically lower in the epidural analgesia group compared to the intravenous analgesia group (p < 0.001). However, there was no significant difference in pain scores (p = 0.422). Additionally, perioperative hypotension requiring treatment, as well as nausea and vomiting, were significantly higher in the epidural analgesia group compared to the intravenous analgesia group (p < 0.001). CONCLUSIONS: Epidural analgesia is superior to intravenous morphine in terms of reducing postoperative opioid consumption within the initial 72 h after open liver resection. Nevertheless, perioperative hypotension, which necessitates management, should be approached with consideration and vigilance. TRIAL REGISTRATION: The study was registered in the Clinical Trials Registry at www. CLINICALTRIALS: gov/ , NCT number: NCT06301932.

High dose opioid agonist therapy for patients with opioid use disorder: a case series exploring this patient-centered approach.

OBJECTIVES: Management of opioid withdrawal in the inpatient setting can vary widely depending on the patient, the physician, and the institution. Although buprenorphine and methadone are first-line therapy for withdrawal management, some patients experience barriers to those medications. In this case series, we explore high dose opioid agonist therapy (HDOAT) as a novel and effective option to bridge to recovery in this particular setting. METHODS: This retrospective case series includes- five patients with opioid use disorder (OUD) who were treated with HDOAT while hospitalized and reports on their outcomes. RESULTS: All five patients completed lifesaving medical therapy, engaged with community health workers for resources, and successfully transitioned to medications for opioid use disorder (MOUD). More importantly, none of the patients had patient directed discharges (PDDs). Furthermore, there were no inpatient drug uses or overdoses requiring naloxone administration, even with very high doses of oxycodone. None of the five patients were readmitted within thirty days. CONCLUSIONS: Although more rigorous research is needed, HDOAT may be a viable strategy for OUD when patients continued to decline buprenorphine or methadone on admission. This case series demonstrated the successful use of this strategy toward preventing PDDs, promoting treatment completion, and allowing substance recovery and rehabilitation, in patients who elected to defer MOUD on arrival.

Pain Management Strategies in Intensive Care Unit: Challenges and Best Practice.

Pain management in the ICU (intensive care unit) is a very complex problem which involves a wide variety of conditions, lack of sufficient tools for use, and high personnel to patient ratio. In the last three decades, pain as a clinical issue has become well analyzed, and treatment protocols based on scientific evidence have been established. Besides medication, some non-pharmacological methods such as music therapy, relaxation, and massage have been proven to be very much practical and manageable in pain management of ICU. The main opioids are utilized predominantly due to their power but NSAIDs and local anesthesia are combined with opioids with the aim to reduce the pain as much as possible. Yet more research now has to prove that pain evaluation and management is effective. This article discusses on the issues and the best approaches to solving them when managing pain in ICU patients.

Bulimia Nervosa and Depression, from the Brain to the Gut Microbiota and Back.

Bulimia nervosa (BN) is a condition marked by a typical cyclical behavioural activity, characterized by restrictions, binges and vomiting, as well as a disturbance of the emotional value of food. Food stimuli acquire excessive relevance, giving rise to a succession of states of excitement and anxiety. The depressive condition accompanies very often BN. Most people with BN also experience one or more anxiety disorders. The aim of the review is to identify a link at a central and peripheral level that connects an eating disorder with a mood state. Altered nervous mechanisms are involved in BN. Among the cerebral areas, the insula is functionally compromised in BN. The insula is also implicated in depressive states. The insula is the primary gustatory cortex, where gustatory sensory information such as taste discrimination and higher cognitive functions such as food anticipation and reward are processed. The insula is anatomically connected to a wide range of cortical, limbic and paralimbic structures, and functionally implicated in high-order cognition, emotional responses, and empathic processes. The insula plays a crucial role in empathy, or in the ability to share the emotional states of others, and in particular negative emotions. In fact, the insular cortex is also activated in conditions of anxiety and depression. One of the pathophysiological factors that influences bulimia and depression is the composition of gut microbiota, as there is a strong association between the microbial signature and the brain function. Gut dysbiosis condition may contribute to the development of eating disorders, including BN. Dysbiosis may promote intestinal inflammation, alter gut permeability, and trigger immune reactions in the hunger/satiety regulation center contributing to the pathophysiological development of eating disorders. From this emerges the importance of adequate probiotic integration as a preventive and/or therapeutic tool in these pathologies.

Linkage facilitation for opioid use disorder in criminal legal system contexts: a primer for researchers, clinicians, and legal practitioners.

At the intersection of drug policy, the opioid crisis, and fragmented care systems, persons with opioid use disorder (OUD) in the United States are significantly vulnerable to contact with the criminal legal system (CLS). In CLS settings, provision of evidence-based treatment for OUD is variable and often secondary to punitive approaches. Linkage facilitation at every touch point along the CLS Sequential Intercept Model has potential to redirect persons with OUD into recovery-oriented systems of care, increase evidence-based OUD treatment connections, and therefore reduce CLS re-exposure risk. Research in this area is still nascent. Thus, this narrative review explores the state of the science on linkage facilitation across the varied CLS contexts, including general barriers, facilitators, and opportunities for using linkage facilitation for OUD treatment and related services. Following the CLS Sequential Intercept Model, the specific CLS contexts examined include community services, police encounters, the courts (pre- and post-disposition), incarceration (pre-trial detention, jail, and prison), reentry (from jails, prisons, and unified systems), and community supervision (probation and parole). Examples of innovative linkage facilitation interventions are drawn from the Justice Community Opioid Innovation Network (JCOIN). Areas for future research and policy change are highlighted to advance the science of linkage facilitation for OUD services in the CLS.

An age-friendly opioid use disorder (OUD) care workshop: applying the 5Ms framework.

Over the last two decades, the rate of fatal overdoses among adults 65 years and older has risen exponentially. Older adults are more vulnerable to opioids yet are less likely to have their opioid use disorder (OUD) recognized and treated. The prevalence of geriatric syndromes is higher among older adults with OUD, yet there is limited attention on how improving current OUD treatment for older adults can address their complex care needs. A case-based workshop was presented at the 2023 Annual Meeting of the Society of General Internal Medicine to provide generalists with training, skills, and resources to care for aging adults with OUD through the lens of the Geriatrics 5 Ms framework. After an introductory background, workshop participants engaged in a 5-part mega-case designed to encourage discussion and empower participants to apply each of the 5 Ms to the care of older adults with OUD. Attendees rated the workshop highly in achieved learning objectives, quality, facilitation, and planned incorporation of learned knowledge to teaching, research, patient care, or administration. An interactive case-based workshop on applying the 5 Ms framework to the care of older adults with OUD is feasible, replicable, and may promote age-friendly care for this patient population.

A review on abuse-deterrent formulations: formulation technology and regulatory stands in approval process.

Drug abuse has become a global health problem over the past few years. Opioid abuse increased with an increase in the prescription of opioids for pain management. Many other classes of drugs are also abused and misused like anti-depressants, stimulants, hallucinogens, anti-psychotic, and anticholinergic drugs. One of the major reasons is that patients falsely diagnosed with depression, anxiety, and severe pain are prescribed these drugs, which are likely to be addictive. Abuse-deterrent formulations are one means to control drug abuse and overdose of prescription opioids. In this review, we explained how abuse-deterrent technology works, key ingredients used in abuse-deterrent formulations, a brief about marketed opioid drug products with abuse-deterrent properties, and the stand of regulatory agencies in the approval process of opioid drug products. In the end, it summarized that pharmaceutical industries and the FDA put their efforts into reducing drug abuse by encouraging the development of ADFs. Most available drug product having abuse-deterrent features contains Polyethylene oxide, which degrades at high temperatures. It requires the attention of the researcher to find an alternate ingredient or process to overcome said problem. From a regulatory point of view, only a few regulatory agencies have published their guidance on ADFs. It is important to convey other regulatory organizations' perspectives on ADFs as well.

Modified thoracoabdominal nerve block via perichondral approach: an alternative for perioperative pain management in laparoscopic cholecystectomy in a middle-income country.

BACKGROUND: Laparoscopic cholecystectomy is known for its minimally invasive nature, but postoperative pain management remains challenging. Despite the enhanced recovery after surgery (ERAS) protocol, regional analgesic techniques like modified perichondral approach to thoracoabdominal nerve block (M-TAPA) show promise. Our retrospective study evaluates M-TAPA's efficacy in postoperative pain control for laparoscopic cholecystectomy in a middle-income country. METHODS: This was a retrospective case-control study of laparoscopic cholecystectomy patients at Hospital General de Mexico in which patients were allocated to the M-TAPA or control group. The data included demographic information, intraoperative variables, and postoperative pain scores. M-TAPA blocks were administered presurgery. OUTCOMES: opioid consumption, pain intensity, adverse effects, and time to rescue analgesia. Analysis of variance (ANOVA) compared total opioid consumption between groups, while Student's t test compared pain intensity and time until the first request for rescue analgesia. RESULTS: Among the 56 patients, those in the M-TAPA group had longer surgical and anesthetic times (p < 0.001), higher ASA 3 scores (25% vs. 3.12%, p = 0.010), and reduced opioid consumption (p < 0.001). The M-TAPA group exhibited lower postoperative pain scores (p < 0.001), a lower need for rescue analgesia (p = 0.010), and a lower incidence of nausea/vomiting (p = 0.010). CONCLUSION: Bilateral M-TAPA offers effective postoperative pain control after laparoscopic cholecystectomy, especially in middle-income countries, by reducing opioid use and enhancing recovery.

Enkephalins and Pain Modulation: Mechanisms of Action and Therapeutic Perspectives.

Enkephalins, a subclass of endogenous opioid peptides, play a pivotal role in pain modulation. Enkephalins primarily exert their effects through opioid receptors located widely throughout both the central and peripheral nervous systems. This review will explore the mechanisms by which enkephalins produce analgesia, emotional regulation, neuroprotection, and other physiological effects. Furthermore, this review will analyze the involvement of enkephalins in the modulation of different pathologies characterized by severe pain. Understanding the complex role of enkephalins in pain processing provides valuable insight into potential therapeutic strategies for managing pain disorders.

Somebody to Lean on: Understanding Self-Stigma and Willingness to Disclose in the Context of Addiction.

Substance use self-stigma is a barrier to treatment and can negatively impact individuals' well-being and treatment engagement. Given the mixed findings in previous research and the limited specific investigation into the concept of self-stigma within the context of opioid misuse, examining factors associated with self-stigma in the context of opioid use disorder (OUD) is warranted. The current study examines the influence of individual-level factors (race, sex, urban/rural status, support group attendance) on self-stigma and willingness to disclose opioid use. Data for this study were from a larger study of OUD-related stigma among adults in Pennsylvania, U.S. The current study included participants who indicated a personal past or current history with OUD were included (n = 84). Exploratory factor analysis and multiple indicators, multiple causes (MIMIC) model were used to explore the associations between demographic factors (i.e., sex, age, race/ethnicity, urban/rural status), attendance at mutual support groups, and self-stigma factors. Results indicated that sex and attendance at mutual support groups significantly predicted levels of self-stigma. Women and individuals with no previous experience attending mutual support groups endorsed lower levels of self-stigma. Additionally, attendance at mutual support groups predicted willingness to self-disclose past and present opioid use. Individuals who reported no history of attending mutual support groups demonstrated less willingness to disclose past and present OUD use compared to participants who were support group attendees. The current research findings enhance the understanding of OUD-related self-stigma by examining its relationship with individual-level factors, disclosure, and attendance to mutual support groups. The results offer insights into the influence of sex and support group attendance on self-stigma and disclosure. These findings have significant clinical implications for developing future interventions and promoting health policy changes.

Decrease in injection and rise in smoking and snorting of heroin and synthetic opioids, 2000-2021.

BACKGROUND: Injecting, smoking, and snorting heroin/synthetic opioids is each associated with unique health risks. It is unclear how route of administration (ROA) preferences have shifted during the opioid epidemic. METHODS: Using 2000-2021 admissions data from SAMHSA TEDS-A, we analyzed trends in heroin/synthetic opioid ROA preferences and factors associated with these preferences. RESULTS: 7,881,318 heroin/synthetic opioid admissions reported injection, smoking, or snorting preference. Nationally, injection peaked in 2014 (69.9 %) and nadired in 2021(52.2 %), snorting nadired in 2014 (24.9 %) and peaked in 2021 (36.4 %), and smoking rose steadily from 2.5 % in 2005 to a peak of 11.4 % in 2021. From 2000-2021, the number of states with ≥10 % smoking rates grew from 2 to 27 (highest: 57.0 % in Arizona in 2021). In 2021, increased adjusted prevalence ratios (APR) of non-injection versus injection use were associated with older age at first opioid use (APR 1.52 [95 % CI: 1.51, 1.54] for those 30+ relative to ≤20), and all race/ethnicities relative to non-Latino White individuals (highest: Black individuals, APR 1.77 [1.75, 1.78]). Geography strongly predicted smoking versus snorting (Mountain APR 6.91 [6.64, 7.19], Pacific APR 6.61 [6.35, 6.88], reference: New England). CONCLUSIONS: ROA preferences of heroin/synthetic opioids have changed substantially since 2000, with: 1) recent decreases in injection nationally; 2) increased smoking, particularly in the western US; and, 3) recent increased snorting in the eastern US. Smoking is now prevalent and growing. Public health implications include an increasing number of smoking-related fatal overdoses and the probable reduction of injection-specific morbidity and increase in smoking-specific morbidity.

A review of possible biomarkers for opioid tolerance.

Knowledge of opioid tolerance in a deceased person is important for distinguishing between therapeutic and toxic opioid concentrations for that particular individual when interpreting postmortem toxicological results. However, no biomarkers for opioid tolerance are currently available. This review aimed to study the existing literature on mechanisms or changes in signaling pathways related to chronic opioid use, which could be relevant for further studies to identify biomarkers for opioid tolerance. We performed a systematic literature search using the PRISMA 2020 guidelines using the MeSH terms "opioid tolerance AND biomarkers" in PubMed, Embase, WebofScience, and the Cochrane library. A review of the search results yielded seven studies on animal models or humans, identifying and evaluating thirteen possible biomarkers in terms of specificity for changes induced by opioids and other aspects to be considered as potential biomarkers. We evaluated nine potential biomarkers as unlikely to be specific for opioid tolerance, and one had contradictory results in terms of upregulation or downregulation. However, methylation of the promoter region of the µ-opioid receptor gene, increased activity of soluble puromycin-sensitive aminopeptidase, altered miRNA profile, or other multiple component profiling may be interesting to study further as biomarkers for opioid tolerance in forensic postmortem cases.

Buprenorphine treatment and clinical outcomes under the opioid use disorder cascade of care.

BACKGROUND: Challenges to engagement and retention on buprenorphine undermine treatment of individuals with opioid use disorder (OUD). Under the OUD Cascade of Care framework, we sought to identify patient characteristics and treatment response associated with superior clinical outcomes. METHODS: A retrospective cohort study of specialty buprenorphine treatment patients entering treatment (n=19,487) based on EHR records from a large multi-state buprenorphine treatment network (2011-2019). Person-level care episodes were evaluated across treatment intake, engagement (i.e. 2+ visits in the month following intake), and retention at 6, 12, and 24 months. Time to achieving 90 days of continuous opioid abstinence was assessed using Cox proportional hazards regressions models and also assessed as a predictor of long-term retention. RESULTS: Most patients engaged (82.4 %), but retention steadily declined over 6-month (38.7 %), 12-month (26.2 %), and 24-month (17.1 %) timepoints. Opioid-positive baseline tests were associated with lower hazards of achieving continuous abstinence for both buprenorphine-positive (aHR=0.33, p<.001) and buprenorphine-negative (aHR=0.49,p<.001) intakes. Opioid abstinence was associated with buprenorphine-positive baseline testing (aHR=1.59,p<.001), especially for those testing opioid-negative (aHR=1.82,p<.001). Patients who achieved and sustained abstinence at 6 months in care were 4.1 and 5.5 times as likely to achieve 12-month and 24-month retention, respectively, compared to patients with intermittent opioid use. CONCLUSION: Treatment discontinuation was concentrated early in care and buprenorphine and opioid status at intake were prognostic of achieving and sustaining abstinence. Early abstinence was associated with higher likelihood of subsequent stage progression. Implementing interventions to support early clinical stability for high-risk patients is critical to improve clinical outcomes.

Elucidating the harm potential of brorphine analogues as new synthetic opioids: Synthesis, in vitro, and in vivo characterization.

The emergence of new synthetic opioids (NSOs) has added complexity to recreational opioid markets worldwide. While NSOs with diverse chemical structures have emerged, brorphine currently remains the only NSO with a piperidine benzimidazolone scaffold. However, the emergence of new generations of NSOs, including brorphine analogues, can be anticipated. This study explored the pharmaco-toxicological, opioid-like effect profile of brorphine alongside its non-brominated analogue (orphine) and three other halogenated analogues (fluorphine, chlorphine, iodorphine). In vitro, radioligand binding assays in rat brain tissue indicated that all analogues bind to the µ-opioid receptor (MOR) with nM affinity. While analogues with smaller-sized substituents showed the highest MOR affinity, further in vitro characterization via two cell-based (HEK 293T) MOR activation (ß-arrestin 2 and mini-Gαi recruitment) assays indicated that chlorphine, brorphine, and iodorphine were generally the most active MOR agonists. None of the compounds showed significant in vitro biased agonism compared to hydromorphone. In vivo, we investigated the effects of intraperitoneal (IP) administration of the benzimidazolones (0.01-15 mg/kg) on mechanical and thermal antinociception in male CD-1 mice. Chlorphine and brorphine overall induced the highest levels of antinociception. Furthermore, the effects on respiratory changes induced by a fixed dose (15 mg/kg IP) of the compounds were investigated using non-invasive plethysmography. Fluorphine-, chlorphine-, and brorphine-induced respiratory depressant effects were the most pronounced. For some compounds, pretreatment with naloxone (6 mg/kg IP) could not reverse respiratory depression. Taken together, brorphine-like piperidine benzimidazolones are opioid agonists that have the potential to cause substantial harm to users should they emerge as NSOs.