Opiate Use Disorder Research Articles

Assessing predictors of adequate individual buprenorphine maintenance dosage for the treatment of opioid use disorder: Listening to the patient

ObjectiveDose optimization plays a key role in determining clinical outcomes in patients on opioid agonist treatment (OAT). The objective of this study was to identify the variables independently associated with buprenorphine/naloxone (B/N) dose adequacy in patients with opiate use disorder (OUD). MethodCross-sectional study of a convenience sample of patients with OUD treated with B/N (n = 315) in four regions in Spain. The Opiate Dosage Adequacy Scale (ODAS) was used to determine B/N dose adequacy. The ODAS evaluate the six components of the “dose adequacy” construct, as follows: continued use of heroin; narcotic blockade or crossed tolerance; objective opioid withdrawal symptoms (OWS); subjective OWS; craving for heroin; and overmedication. A binomial logistic regression analysis was performed to identify the variables associated with the condition “ODAS Adequate B/N dose”. Participants completed a battery of instruments to assess sociodemographic, substance use, clinical, and treatment variables. ResultsThe B/N dose was considered adequate in 231 of the 315 participants (73.3 %). Two variables, satisfaction with B/N as a medication (OR=5.764, 95 % CI=2.211-15.030) and patient-perceived participation in B/N dose decisions (OR=1.790, 95 % CI=1221-2623), were independently, significantly, and positively associated with the “ODAS Adequate B/N dose” condition. While the severity of heroin dependence was significantly associated with buprenorphine dose adequacy in the bivariate analyses, significance was lost in the full regression model. ConclusionSatisfaction with B/N as a medication and patient-perceived involvement in the dose decision are associated with clinician-assessed dose adequacy. In the context of good clinical practice, it is important to take into account both of these variables to individualize the prescribed dose through a shared decision-making process.

The comparison between opiate use disorder patients in the remission state with healthy volunteers regarding behavioral addictions

ABSTRACT Objective The present study aimed to compare the patients with opiate use disorder (OUD) and healthy volunteers with respect to behavioral addictions (gambling, excessive shopping, internet, and exercise). Methods Our study included 100 OUD patients in the remission state for at least one month who had been diagnosed according to DSM-5 diagnostic criteria and completed detoxification therapy and 100 healthy volunteers. Sociodemographic Data Form, South Oaks Gambling Screen (SOGS), Compulsive Online Shopping Scale (COSS), Exercise Addiction Scale (EAS), and Internet Addiction Scale (IAS) were administered to all participants. Results Mean ages were 31.62 ± 6.48 and 31.67 ± 7.8 years in the OUD and healthy volunteer groups, respectively (p = NS). Male participants constituted 90% (n = 90) of both groups. Similar SOGS (p = NS), COSS (p = NS), and EAS (p = NS) scores were detected in both groups. IAS scores of healthy controls were found significantly higher than the OUD group (p < .001). Conclusion According to our study results, we can state that OUD patients in the remission state are similar with general population with respect to exercise, gambling, and shopping addictions whereas their risk for internet addiction is lower than the general population.

Serum brain-derived neurotrophic factor in relation to craving and duration of abstinence in patients with heroin dependence-A case-control study.

Addiction is a chronic disorder that comes with emotional and financial burdens. Several neurobiological factors were correlated to opiate-use disorder which is brain-derived neurotrophic factor (BDNF). BDNF has been found to be involved in long-term potentiation of synaptic strength, a mechanism that is thought to motivate both natural adaption mechanisms as well as the development of addictive behavior. In this study, we aimed to address the relation between BDNF serum level and heroin craving and the effect of duration of abstinence on them. A case study was conducted on 80 subjects from Kasr Al-Ainy Psychiatry and Addiction Treatment Hospital with a history of heroin dependence and were divided into two groups: Group A had 40 active heroin-dependent subjects while in Group B, 40 subjects with 1-year heroin abstinence. Severity of addiction was assessed by the addiction severity index, heroin craving was measured by Brief Substance Craving Scale and serum BDNF level was investigated using an enzyme-linked immunosorbent assay. The findings show that active heroin users had significantly higher serum BDNF which is associated with high heroin craving in comparison to the abstinent group. This study revealed a significant positive correlation between serum BDNF levels and craving in active heroin users versus 1-year abstinent subjects. It is the first study to address the relationship between craving and serum BDNF level in a 1-year abstinent participants. These findings help to determine the brain alterations associated with illness and recovery in heroin dependence.

Opiate Use Disorder and Exercise: A Systematic Review

Background: The opiate epidemic continues to cause hardship to American communities, including in all counties in Ohio, and resulted in 100 000 drug overdoses in 2021. Medications such as buprenorphine have helped people affected by opiate use disorder (OUD) to continue through recovery, although medication assisted therapy (MAT) has shown limited retention rates, calling for complimentary interventions to be implemented. Exercise has potential to reduce cardiovascular risk, lower obesity, and improve mental health. The aim of this study is to systematically review the literature on OUD and exercise as an adjunct to MAT. The authors hypothesize that there is a gap in the knowledge as to whether this modality has been thoroughly researched to aid in OUD recovery.Methods: A database literature search of PubMed, CINHAL, and PsychInfo returned a total of 458 abstracts. Four sets of exclusion criteria were implemented resulting in a total of 26 articles. After further review, 8 more articles were excluded by the authors.Results: Eighteen articles including participants with OUD were systematically reviewed. Only 1 article solely fo-cused on participants with OUD and exercise as an adjunct to treatment.Conclusion: Exercise as an adjunct to treatment for OUD is an area of addiction treatment that warrants further investigation. Incorporating exercise into a recovery program for people with substance use disorders (SUD) specifically has been touted as a promising modality, however, limitations in OUD only studies and lack of control groups make it difficult to draw a conclusion to support our hypothesis.

EPD1504: a novel μ-opioid receptor partial agonist attenuates obsessive-compulsive disorder (OCD)-like behaviors.

Low doses of μ-opioid receptor (MOR) agonists rapidly ameliorate symptoms in treatment-resistant obsessive-compulsive disorder (OCD) patients (10-50% of OCD patients). However, the utility of MOR agonists is limited by their safety liabilities. We developed a novel MOR partial agonist (EPD1540) that has an improved respiratory safety profile when compared to buprenorphine. Buprenorphine is a MOR partial agonist primarily used in the treatment of opiate-use disorder, which in investigator-led trials, has been shown to rapidly ameliorate symptoms in treatment-resistant OCD patients. In this study, we show that doses of EPD1504 and buprenorphine that occupy small fractions of MORs in the CNS (approximately 20%) are as effective as fluoxetine at ameliorating OCD-like behaviors in two different rat models (an operant probabilistic reversal task and marble burying). Importantly, effective doses of EPD1504 did not impair either locomotor activity, or respiration under normoxic or hypercapnic conditions. Additionally, EPD1504 had effects comparable to buprenorphine in the conditioned place preference assay. These results indicate that EPD1504 may provide a safer alternative to buprenorphine for the treatment of OCD patients.

Drug use in pregnancy in Ireland’s capital city: A decade of trends and outcomes

ObjectiveThe aim of this study was to present contemporary trends in opiate use disorder (OUD) and substance use in pregnancy in Ireland, with associated obstetric outcomes, over the last ten years. Study designThis retrospective observational cohort study was conducted at an Irish tertiary maternity unit. All women with OUD or substance use in pregnancy delivered under this service between 2010 and 2019 were included. Drug-exposure was self-reported. Data was collected by combining electronic and hand-held patient records. Trends and outcomes were analysed by year of delivery. Approval for the study was granted by the institution’s clinical governance committee. ResultsOf the 82,669 women delivered, 525 had OUD or substance use in pregnancy (1 in every 160 women booking). 11.6% were homeless, 20.0% were in full-time employment and 91.0% smoked tobacco in pregnancy. 66.3% had a history of psychiatric disorders.Over the ten years, there was a significant reduction in women delivered with OUD or substance use in pregnancy (0.8 % to 0.4 %, RR 0.55, 95 % CI 0.36–0.85), significant reduction in the proportion of women on Opioid-Substitute-Treatment (OST, RR 0.66 95 % CI 0.51–0.87) and an increase in mean maternal age (30.7to32.0 years). Rates of cocaine and cannabis consumption increased (20.6 %, RR 3.8, 95 % CI 1.57–9.44: 24.0 %, RR 3.7, 95 % CI 1.58–8.86 respectively).The maternal mortality rate was 380.9:100,000 births. The perinatal mortality rate was 15.6:1000 births. The preterm birth rate was 17.9 %, with a mean birth weight of 2832 g. The rate of NICU admission was 52.0 % and the mean length of stay was 22.4 days. Amongst the smaller OUD population, the rate of NICU admission for Neonatal Abstinence Syndrome (NAS) and treatment for NAS increased over the study timeframe (36.0 %, RR 2.97, 95 % CI 1.86–4.75: 28.5 %, RR 2.92, 95 % CI 1.70–5.0 respectively). ConclusionsThe obstetric population attending an Irish antenatal service with opiate use disorder or substance exposure is reducing in size with older patients, less opioid substitute therapy and increasing cocaine and cannabis use. These women have high rates of maternal and perinatal morbidity and mortality. Specialist antenatal addiction services, coordinated by the drug-liaison midwife, are critical in adapting care to respond to this dynamic and vulnerable patient cohort.

Second to fourth digit ratio (2D:4D), impulsivity and aggression levels in patients with opiate use disorder and alcohol use disorder

ABSTRACT Objective To compare the ratio of the right and left second and fourth digits (2D:4D), aggression, and impulsivity levels in opiate use disorder (OUD), alcohol use disorder (AUD), and healthy controls. Methods Eighty-four patients diagnosed with OUD, 58 patients diagnosed with AUD, and 58 healthy volunteers were included. Participants administered the sociodemographic data form, Barratt Impulsivity Scale (BIS-11), and Buss-Perry Aggression Questionnaire (BPAQ). Results Healthy controls’ right-hand 2D:4D ratio was higher than the OUD and AUD groups (respectively; p < .001, p < .001). The right-hand 2D:4D ratio was similar between OUD and AUD (p = .542). Left-hand 2D:4D ratio of healthy controls was higher than OUD and AUD groups (respectively; p < .001, p < .001). The left-hand 2D:4D ratio was similar between OUD and AUD (p = .429). The BIS-11 scores of the healthy controls were lower than OUD and AUD groups (respectively; p < .001, p < .001). It was found similar in the AUD and OUD groups (p = .264). The BPAQ scores of the healthy controls were lower than the OUD group and the AUD group (respectively; p < .001, p < .001). It was found similar in the AUD and OUD groups (p = .973). Conclusion It was found that the 2D:4D ratio of both hands in OUD and AUD patients is lower than that of healthy volunteers. The 2D:4D ratio can be an indicator of addiction, regardless of the type of substance used.

Elevated serum lead levels in neonates born to mothers suffering from opiate use disorder.

This study was performed to investigate lead levels in neonates born to the mothers suffering from opiate use disorder (OUD) and the association of lead levels with the Apgar score. The present cross-sectional study included 56neonates who were referred to the neonatal ward of Amir-Al Momenin Hospital, Zabol. The neonates were divided into two groups: the neonates whose mothers suffered OUD and the control group. Data were collected using aresearcher-prepared questionnaire, and blood lead level was determined using the atomic absorption method. Data were statistically analyzed. In all, 56neonates (28from OUD mothers and 28from the control mothers) were included in this study. Among the women with OUD, 16 (57%) used inhaled opium, while12 (43%) consumed opium orally. There was asignificant difference regarding Apgar score (9.76 ± 2.11 versus. 7.11 ± 4.21; p = 0.02) and the neonate's blood lead level (2.33 ± 1.3 µg/dl versus 7.33 ± 5.9 µg/dl) between the control and OUD groups (p < 0.001). The odds ratio of abnormally elevated blood lead level rose with increasing duration of maternal opiate disorder for opiate usage durations of 3to 5years (adjusted odds ratio [OR] 42.82, 95% confidence interval [CI] 3.27-561, p = 0.004) and > 5years (adjusted OR 45.5, 95% CI 2.97-698, p = 0.006). The results of this study suggested asignificant relationship between maternal opium consumption during pregnancy and neonatal serum lead levels, as well as decreased neonatal Apgar score.

907. The HCV Care Continuum Among Hospitalized Persons Who Inject Opiates: Missed Opportunities for Screening and Referral to Treatment

Abstract Background Despite an effective cure, hepatitis C virus (HCV) remains a major public health problem for persons who inject opiates. Hospitalization provides an opportunity to identify chronic HCV infection and provide referral and linkage to outpatient care upon discharge. We examined the HCV care continuum among hospitalized persons who inject drugs and have opiate use disorder (OUD). Methods The CHOICE Study is a retrospective chart review of adults hospitalized with infectious complications of OUD and injection drug use at four academic medical centers (University of Maryland, George Washington University, University of Alabama, and Emory University). The sample included patients hospitalized between 1/1/2018-12/31/2018, had ICD9/10 diagnosis codes consistent with OUD and acute bacterial/fungal infection, and chart review verification of active infection associated with OUD. Data on HCV antibody (Ab) and RNA testing and referral to HCV treatment within the medical system were abstracted from medical records. Results Of 287 patients, median age was 40 (IQR: 32-52), 59% were male, and 63% were white and 34% black. Overall, 38% (n=108) had known HCV infection at hospitalization; of those with unknown status, only 41% (n=73) were screened for HCV. Among those, 67% were HCV Ab+. Of patients who were HCV Ab+ or had known HCV infection (n=157), only 52% were tested for HCV RNA, of whom 61% had detectable RNA. Only 40% of those with detectable RNA received a treatment referral prior to discharge (Fig. 1). The length of stay of the admission was not associated with treatment referral, but a shorter length of stay was significantly associated with not being screened for HCV Ab or RNA tested (p&amp;lt; 0.05). Of five patients who were referred to care within the medical system, four initiated HCV treatment, and two achieved known sustained viral response. Figure 1. HCV Continuum of care for hospitalized patients who inject drugs with opioid use disorder (OUD) at four academic medical centers in the United States, January 2018-December 2018 Conclusion Hospitalization is a missed opportunity for HCV screening and linkage. Despite opportunities to address HCV infection among this highly impacted population, there were sizeable gaps in the HCV continuum of care among hospitalized persons who inject opiates. Structural reasons such as length of stay may be a factor in implementing HCV testing. Disclosures Sarah Kattakuzhy, MD, Gilead Sciences (Scientific Research Study Investigator, Research Grant or Support) Ellen Eaton, MD , Gilead (Grant/Research Support) Ellen Eaton, MD , Gilead (Individual(s) Involved: Self): Research Grant or Support Greer A. Burkholder, MD, MSPH, Eli Lilly (Grant/Research Support) Elana S. Rosenthal, MD, Gilead Sciences (Research Grant or Support)Merck (Research Grant or Support)

Emergency Physicians Ability to Recognize and Diagnose Opiate Use Disorder: A Qualitative Study.

IntroductionThe opioid crisis is a significant public health problem for this generation. Proper treatment of patients with opiate use disorder (OUD) during vulnerable times is vital to their engagement in opiate agonist therapy (OAT). There is limited information as to the efficacy of ED practitioners in recognition of opioid withdrawal or OUD; this research was designed to fill this gap to advance our care of vulnerable populations.MethodsInterviews were conducted with seven convenience-sampled ED physicians and nurse practitioners from the Saint John Regional Hospital by providing a clinical vignette. These one-on-one, scripted interviews, conducted by the principal and co-investigator, tell us about the ED physician’s understanding of OUD and withdrawal by posing questions around the presentation within the clinical vignette, as well as around general knowledge of OUD and acute withdrawal.ResultsAll seven participants identified the patient in the case as being in opioid withdrawal but did not identify all symptoms in the vignette. Two correctly diagnosed our patient as having OUD based on the scene provided. Five physicians identified criteria that pointed toward this diagnosis but did not vocalize the connection. Only one discussed prescription of OAT as a treatment, most opting for symptom management and information on sites of self-referral for treatment. Finally, six of our interviewees expressed interest in prescribing buprenorphine but cited a need for more education around its use and initiation before feeling comfortable prescribing it.ConclusionsWhile ED practitioners correctly recognize opiate withdrawal, there is a knowledge gap in the related diagnosis and evidence-based management of OUD. The development of education around these gaps will allow for stronger advocacy and better outcomes for this patient population.

Comparison of naltrexone implant and oral buprenorphine-naloxone in the treatment of opiate use disorder.

We aimed to compare the effectiveness of extended-release naltrexone (XR-NTX) implant and sublingual buprenorphine-naloxone (BUP-NX) in relapse prevention in opiate use disorder (OUD). Medical records of 400 patients who were treated for OUD between 2016 and 2020 were retrospectively evaluated concerning sociodemographic and clinical characteristics and abstinence duration with either BUP-NX (192 patients) or XR-NTX (208 patients) as maintenance treatments. The median age of patients using BUP-NX was 25.00, and the median age of patients using XR-NTX was 25.50 (p=.785). The ratio of female patients in the BUP-NX group and the XR-NTX group was 7.3% (n=14) and 6.7% (n=14), respectively. A significantly higher abstinence time was observed in the BUP-NX group (median=4months) than in the XR-NTX group (median=3months) (p=.015). Liver function tests were within the normal ranges at the three time points, which were just before the beginning and in the first and third months of treatment. These findings suggest that BUP-NX might be more effective than XR-NTX in preventing relapse in OUD and both drugs are safe for the liver. Prospective randomized studies are needed to replicate our results.

Evaluation of Applications to an Alcohol and Substance Dependence Treatment and Training Centre (AMATEM): Data from Adiyaman Province in 2017

Objective: Substance use disorder (SUD) continue to be a problem for the whole world in the first quarter of the twenty-first century. The leading centres in the treatment of SUD in our country are the Alcohol-Drug Addiction Research Treatment and Training Centres (AMATEM). In this study, we aimed to examine 2017 data of the AMATEM outpatients in our province. Material and Methods: The study was conducted as a retrospective study of AMATEM applications between January 1, 2017 and December 31, 2017. Information such as gender, age and substance use characteristics of the applications were obtained from the patient recording system. Results: A total of 211 applications were reached. The rate of men was 95.7%, female rate was 4.3%, and the mean age was 26.09±7.87 years. The mean age was significantly higher in patients with alcohol use disorder than in the other diagnoses. 86.4% of the patients were in the 20-29 age range. 80.1% of the patients were diagnosed with opiate use disorder (OUD). The repeated applications were significantly higher in OUD than in other applicants. The rate of prescribing of buprenorphine+naloxane in OUD was 73.4%. Buprenorphine, buprenorphine+opiate and opiate positivity was higher than other parameters in urine toxic screening. In OUD, substance positivity in urine was significantly higher in non-opiates than in non-opiates. Conclusion: This study is important in terms of revealing that opiate use is a serious problem in our province. At the same time, as far as we know, it is the first study of AMATEM outpatient data in our province. Further studies are needed in this field.

Sociodemographic and clinical characteristics of patients with long-term remission with buprenorphine / naloxone in opiate use disorder

IntroductionBuprenorphine/Naloxone (BP/NLX) is an effective drug combination used in long-term maintenance therapy in opiate use disorder (OUD). In some studies, abstinence over 180 days was defined as long-term remission (1).ObjectivesThe aim of this study is to determine the sociodemographic and clinical characteristics of patients in long-term remission with BP/NLX.Methods In this study, 30 patients who were followed up with OUD at Akdeniz University Addiction Center and were in remission with BP/NLX for at least 180 days were evaluated retrospectively.ResultsSociodemographic and clinical characteristics are summarized in table 1.ConclusionsOUD is associated with lower quality of life and employment rate (2). In our study, the rate of working in a regular job is high. It can be concluded that prolonged remission improves functionality in patients. Although patients are in remission for a long time in terms of opiate use, 20% of patients continue to use cannabis and 10% continue to use cocaine. In a study, there was no difference in productivity and quality of life between BP users with and without current cannabis use. Continued use of cannabis by patients may be related to this condition. However, cannabis use increases many mental illnesses, especially psychosis (4). In patients in remission with BP/NLX, studies should also be carried out to avoid other substances than opiates. In our study, in accordance with the literature (5), no negative effects on kidney and liver functions were observed with long-term BP/NLX treatment. BP/NLX appears to be safe in prolonged use.DisclosureNo significant relationships.

115 Screening and infection rates for hepatitis C virus (HCV) in pregnancy with opiate use disorder

American College of Obstetricians and Gynecologist recently updated recommendation for universal hepatitis C virus (HCV) screening during pregnancy. Previously, HCV screening was recommended in high risk populations. We sought to determine if recommended HCV screening in women with opiate use disorder (OUD) led to appropriate evaluation of HCV infection in pregnant women. This is a retrospective cohort study of pregnant women requiring inpatient management opioid use at a tertiary referral hospital in Pennsylvania identified by ICD-9 coding from 2011-2018. Readmission encounters during the same pregnancy were excluded. HCV antibody, HCV RNA, AST, and ALT test results as well as participant’s knowledge of prior HCV infection were extracted from the electronic medical record. Of the 200 women had detailed chart reviews, 167 were tested for HCV antibody (83%) and 117 (70%) had positive test results. In women who tested positive for HCV, 94 (80%) had no prior knowledge of HCV infection. For those with positive HCV Ab only 30% (35) had viral load assessment on admission or during their current pregnancy and liver enzymes were assessed in 28% (n=33) of patients. In women who were appropriately tested for liver function, 21% had transaminitis (ALT > 54 and/or AST >41) regardless of symptomatology. Pregnant women with OUD have high rates of HCV, screening during pregnancy identifies the diagnosis. Only a minimum of patients identified as having HCV are appropriately evaluated for viral burden and liver function. Despite recommendations for screening, there remains gaps in care in screening and appropriate evaluation for HCV.

40. The Impact of Medically Assisted Therapy for Opiate Use Disorder in staphylococcus Aureus Bacteremia Patients Within a Large Hospital System - A Retrospective Cohort Study

BackgroundIntravenous drug use (IVDU) is a risk factor for development of S. aureus bacteremia (SAB) and prevalent in opiate use disorder (OUD). While the standard of care involves treating the underlying OUD with medically assisted therapy (MAT), it is unknown how much impact this has on clinical endpoints.MethodsWe conducted a retrospective cohort study of patients with IVDU with hospitalizations for SAB during a 28-month period from 9/2016 through 12/2018 in 10 urban and rural North Carolina hospitals in a single large health system. We compared outcomes for patients receiving prescription for MAT at discharge versus no MAT at discharge. MAT was defined as receiving methadone, buprenorphine, or naltrexone. Patients who expired inpatient were excluded from analysis. Clinical endpoints were 30- and 90-day mortality and 30-day SAB-related readmissions.ResultsOf the 174 patients, 28% received a prescription for MAT at discharge. The majority of the patients were Caucasian (88%), female (57%), with mean age of 37 years. Factors that significantly increased likelihood of MAT at discharge were female gender (34% vs 20%, p=0.04), having a complicated SAB (33% vs 28%, p=0.01), presence of a spinal/epidural abscess (57% vs 43%, p=0.002), and increased length of stay (LOS) (37 days vs 24 days, p=< 0.001). No difference in 30- and 90-day mortality was observed; only one patient in each group died within 90 days. Prescription for any MAT at discharge was associated with a significant decrease in the risk of SAB-related 30-day readmission (0% vs 17%, p=0.002).Table 1: Baseline Characteristics Table 2: MAT & Clinical Outcomes in S. aureus Bacteremia Figure 1: Medically Assisted Therapy Prescribed at DischargeConclusionGender, more complicated infections, and prolonged LOS may increase the likelihood of receiving a prescription for MAT at discharge. MAT prescription at discharge may decrease the risk of 30-day SAB related readmission (NNT 5.9). The results suggest that provision of MAT to patients with SAB and history of IVDU should be incorporated into standardized treatment guidelines. Disclosures All Authors: No reported disclosures

Treatments to Combat Opiate Dependence

The current opioid epidemic is a pressing public health concern that has been difficult to address because there is no generally accepted hypothesis to explain the underlying neurophysiological mechanism(s) that lead to tolerance and withdrawal, which in turn could serve as the basis for developing therapeutic interventions. As a step to developing such a unifying mechanistic hypothesis we studied both the electrophysiological firing patterns of individual neurons and behaviors indicative of tolerance and withdrawal in rats following chronic administration of morphine. Neuronal activity recordings from the ventral tegmental area (VTA), nucleus accumbens (NAc), prefrontal cortex (PFC), thalamus, hypothalamus, hippocampus (HIPP), Amygdala (AMYG) and caudate nucleus (CN) following exposure of repetitive (chronic) morphine produced a new baseline pattern of neuronal firing rates, which we refer to as an “opioid-induced pattern” in the mesocorticolimbic neuronal activity circuit, which is thought to be involved in mediating the “reward” effects of opioid and other drugs of abuse. These changes in neuronal firing rate was paralleled by behavioral changes indicative of the development of dependence such as tolerance and withdrawal suggesting a possible cause-effect relationship between the opioid induced pattern change of baseline neuronal firing and the development of opioid tolerance and withdrawal. Briefly, (i) morphine produces a new baseline pattern of neuronal firing (i.e., an “opioid-induced pattern”), (ii) there is an intrinsic neurophysiological mechanism that seeks to maintain newly established patterns of baseline neuronal firing once established, (iii) continued morphine administration maintains the new pattern of baseline neuronal activity so that withdrawal behaviors do not occur, but (iv) eventual discontinuation of the drug leads to opioid withdrawal symptoms. Consistent with this proposed hypothesis, co-administration of the immunomodulator such as interferon, cyclosporin and cortisol attenuated both the development of an altered baseline pattern of neuronal firing and the parallel behavioral changes. This observation suggests that immunomodifiers treatment to morphine dependence subject restore the neuronal firing rate to its pre-morphine baseline and thus alleviate the withdrawal symptoms that make is so difficult for addicts to discontinue opioid use. The studies in this review describe in more detail the findings that led to our proposed hypothesis for the underlying neurophysiological basis of the development of opioid tolerance and withdrawal and the possible use of immunomodulators to decrease the development of dependence and thereby attenuate withdrawal symptoms that make it so difficult for addicts to discontinue drug use. Repetitive use of opioids results in dependence on the drug, a complex condition that is considered to be an opiate use disorder (OUD). The reduction or cessation of opioid consumption leads to severe withdrawal behaviors. The degree of opiate dependence can be assessed by the intensity of the withdrawal behavior. To prevent this devastating opiate withdrawal syndrome, the subject will continue to take the drug. Success in modifying the withdrawal behavior may shed light on the dynamics of OUD and help to curb the opiate epidemic. Classical therapeutic addiction research has focused on cellular and molecular alterations within neurons and their neuronal circuits. As such, most of the pharmacotherapies for opioid addiction are designed to target the neuronal processes known to be affected by drug intake. In addition to the pivotal role of neurons in the initiation, transition, and maintenance of opioid dependence, the glial cells within the central nervous system are also of particular importance. According to some studies, 60 to 80% of the cellular brain is composed of glial cells. Recent studies have shown that glial cells participate in synaptogenesis, neuronal excitability, and neurotransmission. Following opioid exposure, glial cells demonstrate robust changes in their morphology and physiology in key central nervous system regions known to contribute to drug dependence. They play a pivotal role in opioid-addiction like behaviors. Glial cells are also part of the immune system. This review summarizes studies demonstrating that the immune system participates in the expression of opiate withdrawal and that a single dose of immunological substances such as α-interferon, cyclosporine, or cortisol significantly attenuates the severity of the naloxone-induced withdrawal symptoms in opioid-dependent animals. These preclinical studies provide a new approach to treat opiate dependence using immunomodulators that do not belong to the opiate family. We hope that this review will encourage translational studies to use immunomodulators in combating the opioid epidemic and save lives.

57EMF X-Waiver Training for Resident Physicians Increases Emergency Department Buprenorphine Delivery: An Implementation Science Evaluation

Study Objectives: Despite a growing awareness of the opiate epidemic, access to comprehensive care for opiate use disorder (OUD) remains a challenge Buprenorphine administration in acute opioid withdrawal can lead to improved outcomes for patients with OUD, increased follow up with addiction treatment, reduced illicit drug use and lower medical system costs for drug related ED visits Emergency providers may serve to provide an induction to medication-assisted therapy (MAT), decreasing the risk of use after discharge, and referring patients to outpatient MAT providers However, across the spectrum of practice, there continue to be barriers to utilization of buprenorphine, including fears of precipitating withdrawal, fears of diversion or overdose, and beliefs that additional licenses are needed to offer treatment Residents in training have been shown to carry forward practices learned in residency;thus, targeting educational interventions to these emerging physicians has the potential to affect downstream practice patterns and improve patient care Methods: LAC+USC is an urban, tertiary care facility with a large emergency medicine residency We conducted X-waiver training for all emergency residents, which concluded in January of 2020 We examined the number of residents who obtained their X-waiver following the training and changes in patient care including the number of patients dosed with buprenorphine in the ED for withdrawal, buprenorphine prescriptions, and naloxone prescriptions Given nationwide changes in volume of patients seen in the ED during the coronavirus pandemic, the denominator used for these comparisons was per 1,000 ED patient visits Results: Prior to the X-waiver training, there were three X-waivered residents in the department 54 residents completed X-waiver training, and as of March 2020, 17 residents were X-waivered We saw marked increases in buprenorphine treatment and prescribing after the X-waiver intervention (see figure 1) These increases in treatment observed for OUD patients persisted while adjusting for ED volumes Conclusion: The X-waiver training effectively and markedly improved rates of buprenorphine and naloxone delivery to patients with OUD As the opiate epidemic continues to smolder, it will continue to be important to guide resident practice to comprehensive care for OUD This intervention provides a quantitative roadmap of MAT adoption for programs who provide X-waiver programming for residents [Formula presented]

84 The Opioid Epidemic Meets the Coronavirus Pandemic: Rates of Emergency Department Visits for Opiate Use Disorder during COVID-19

There is growing evidence that medication assisted therapy (MAT) which includes buprenorphine can lead to improved outcomes for patients with opiate use disorder (OUD), increased follow up with addiction treatment programs, as well as reduced illicit drug use and medical system costs for drug related emergency department (ED) visits. Emergency providers may serve to provide an induction to MAT and referrals to outpatient MAT providers. However, there continue to be barriers to utilization of buprenorphine from the ED including fears of precipitating withdrawal, fears of diversion or overdose, and beliefs that additional licenses are needed to offer treatment.

Treatment Outcomes and Subsequent Healthcare Utilization Among Patients With Injection Drug Use–Associated Endocarditis

Background: Addiction medicine consultation and medication-assisted treatment (MAT) have been promoted as a way to improve outcomes for patients hospitalized with injection drug use–associated endocarditis (IDU-IE). However, IDU-IE outcomes have not been evaluated in settings where these services are commonplace. Objective: In this study, we evaluated IDU-IE outcomes in a setting where involvement of addiction medicine consultants and use of MAT is well integrated into patient care. Methods: Medical records of patients hospitalized with a diagnosis of bacteremia or infective endocarditis (IE) between October 1, 2015, and December 31, 2017, at a safety-net hospital in Boston were screened for evidence of active injection drug use (IDU) within 6 months of hospitalization (as documented by providers or as supported by urine toxicology assays) for suspected or definite IE using modified Duke criteria. Patients without active IDU or IE were excluded, as were those with a diagnosis of IDU-IE over the 6 months prior to the index hospitalization. Demographic parameters, receipt of antibiotics and MAT, other clinical information, and details of rehospitalizations were recorded. Analyses of descriptive statistics were performed. Results: Of 567 subjects screened for inclusion, 47 patients met inclusion criteria. All had opiate use disorder (OUD); 41 patients (87.2%) had polysubstance abuse. Addiction medicine consultation was completed for 41 patients (87.2%). Of the 47 subjects, 23 patients (54.8%) received MAT (methadone or buprenorphine/naloxone) over their entire hospitalization, and 31 patients (73.8%) received MAT for &gt;75% of the index admission. Moreover, 43 patients (91.5%) survived to discharge, of whom 28 (59.6%) completed antibiotic therapy. Relapsed IDU was observed in 33 patients (76.7%). Relapsed IDU trended toward significance among undomiciled patients (OR, 4.07,; 95% CI, 0.93–17.85; P = .06). Also, 24 patients (55.8%) were rehospitalized within 1 year due to infectious complications of IDU; undomiciled patients were readmitted more frequently (OR, 20.45; 95% CI, 1.09–383.99; P = .04). Completion of IDU-IE antibiotic therapy, relapse of IDU, and rehospitalization were not associated with prior AMA discharges, duration or variety of IDU, receipt of MAT during the index admission, or addiction medicine consultation. The rate of readmission due to an infectious complication of IDU within 1 year was unrelated to the proportion of hospital days where MAT was prescribed. Conclusions: In settings with high rates of addiction medicine consultation and in-hospital MAT administration, inpatient interventions targeting OUD may not necessarily be protective against morbidity and rehospitalization. Focusing on housing instability and outpatient continuation of MAT may be beneficial.Funding: NoneDisclosures: None

A rapid access to addiction medicine clinic facilitates treatment of substance use disorder and reduces substance use

BackgroundSubstance use is prevalent in Canada, yet treatment is inaccessible. The Rapid Access to Addiction Medicine (RAAM) clinic opened at the University Health Network (UHN) in January 2018 as part of a larger network of addictions clinics in Toronto, Ontario, to enable timely, low barrier access to medical treatment for substance use disorder (SUD). Patients attend on a walk-in basis without requiring an appointment or referral. We describe the RAAM clinic model, including referral patterns, patient demographics and substance use patterns. Secondary outcomes include retention in treatment and changes in both self-reported and objective substance use.MethodsThe Electronic Medical Record at the clinic was reviewed for the first 26 weeks of the clinic’s operation. We identified SUD diagnoses, referral source, medications prescribed, retention in care and self-reported substance use.ResultsThe clinic saw 64 unique patients: 66% had alcohol use disorder (AUD), 39% had opiate use disorder (OUD) and 20% had stimulant use disorder. Fifty-five percent of patients were referred from primary care providers, 30% from the emergency department and 11% from withdrawal management services. Forty-two percent remained on-going patients, 23% were discharged to other care and 34% were lost to follow-up. Gabapentin (39%), naltrexone (39%), and acamprosate (15%) were most frequently prescribed for AUD. Patients with AUD reported a significant decrease in alcohol consumption at their most recent visit. Most patients (65%) with OUD were prescribed buprenorphine, and most patients with OUD (65%) had a negative urine screen at their most recent visit.ConclusionThe RAAM model provides low-barrier, accessible outpatient care for patients with substance use disorder and facilitates the prescription of evidence-based pharmacotherapy for AUD and OUD. Patients referred by their primary care physician and the emergency department demonstrated a reduction in median alcohol consumption and high rates of opioid abstinence.