Probing different paradigms of morphine withdrawal on sleep behavior in male and female C57BL/6J mice.

Opioid misuse has dramatically increased over the last few decades resulting in many people suffering from opioid use disorder (OUD). The prevalence of opioid overdose has been driven by the development of new synthetic opioids, increased availability of prescription opioids, and more recently, the COVID-19 pandemic. Coinciding with increases in exposure to opioids, the United States has also observed increases in multiple Narcan (naloxone) administrations as a life-saving measures for respiratory depression, and, thus, consequently, naloxone-precipitated withdrawal. Sleep dysregulation is a main symptom of OUD and opioid withdrawal syndrome, and therefore, should be a key facet of animal models of OUD. Here we examine the effect of precipitated and spontaneous morphine withdrawal on sleep behaviors in C57BL/6 J mice. We find that morphine administration and withdrawal dysregulate sleep, but not equally across morphine exposure paradigms. Furthermore, many environmental triggers promote relapse to drug-seeking/taking behavior, and the stress of disrupted sleep may fall into that category. We find that sleep deprivation dysregulates sleep in mice that had previous opioid withdrawal experience. Our data suggest that the 3-day precipitated withdrawal paradigm has the most profound effects on opioid-induced sleep dysregulation and further validates the construct of this model for opioid dependence and OUD.

Managing acute opioid withdrawal with tramadol during COVID-19 lockdown in a peri-urban setting.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has highlighted the scope of heroin dependence and need for evidence-based treatment amongst marginalised people in South Africa. Acute opioid withdrawal management without maintenance therapy carries risks of increased morbidity and mortality. Due to the high costs of methadone, Tshwane's Community Oriented Substance Use Programme (COSUP) used tramadol for opioid withdrawal management during the initial COVID-19 response. AIM: To describe demographics, route of heroin administration and medication-related experiences amongst people accessing tramadol for treatment of opioid withdrawal. SETTING: Three community-based COSUP sites in Mamelodi (Tshwane, South Africa). METHODS: A retrospective cross-sectional study was conducted. Data were collected using an interviewer-administered paper-based tool between April and August 2020. Descriptive statistics were used to analyse data. RESULTS: Of the 220 service users initiated onto tramadol, almost half (n = 104, 47%) were not contactable. Fifty-eight (26%) people participated, amongst whom most were male (n = 55, 95%). Participants' median age was 32 years. Most participants injected heroin (n = 36, 62.1%). Most participants experienced at least one side effect (n = 47, 81%) with 37 (64%) experiencing two or more side effects from tramadol. Insomnia occurred most frequently (n = 26, 45%). One person without a history of seizures experienced a seizure. Opioid withdrawal symptoms were experienced by 54 participants (93%) whilst taking tramadol. Over half (n = 38, 66%) reported using less heroin whilst on tramadol. CONCLUSION: Tramadol reduced heroin use but was associated with withdrawal symptoms and unfavourable side effects. Findings point to the limitations of tramadol as opioid withdrawal management to retain people in care and the importance of access to first-line opioid agonists.Contribution: This research contributes to the limited data around short-acting tramadol for opioid withdrawal management in the African context, with specific focus on the need for increased access to opioid agonists for those who need them, in primary care settings.

[Delirium, catatonia and substance withdrawal syndrome manifested as psychomotor agitation in COVID-19: a pharmacological management approach for the general hospital setting]. / Delirium, catatonía y síndrome de abstinencia manifestados como agitación psicomotora en COVID-19: una propuesta de manejo farmacológico en el hospital general.

BACKGROUND: Neuropsychiatric symptoms can be part of the clinical spectrum of COVID-19 infections. AIM: To devise an evidence based clinical algorithm as a guide for clinicians, to identify and treat underlying clinical syndromes of psychomotor agitation, such as delirium, catatonia or substance withdrawal in patients who are hospitalized and infected with SARS-CoV-2. MATERIAL AND METHODS: A review of the literature about the pharmacological management of neuropsychiatric manifestations of COVID-19 at the general hospital, to develop a clinical protocol based on a consensus from an interdisciplinary expert panel at a Clinical Hospital. RESULTS: A consensual clinical algorithm for the management of delirium, catatonia, and substance withdrawal, manifested as psychomotor agitation in patients hospitalized with COVID-19, was developed as a clinical proposal for physicians at different levels of complexity in health services. CONCLUSIONS: Cooperation among different clinical units in the general hospital facilitated the implementation of a clinical algorithm for clinicians for the management of psychomotor agitation in COVID-19 patients.

A Case of Phenibut Directed Detoxification Leading to Toxicity During the COVID-19 Pandemic.

BACKGROUND: Phenibut is a non-Food and Drug Administration-approved gamma-aminobutyric acid analog marketed in the United States as an anxiolytic, cognitive enhancer, and alcohol withdrawal treatment through online supplement vendors. In this case report, we describe a woman's self-directed detoxification with phenibut used to manage withdrawal symptoms from fentanyl and benzodiazepines in March 2020 during the height of the COVID-19 pandemic. CASE: A 38-year-old woman with severe opioid, benzodiazepine, gabapentin, stimulant use disorders developed altered mental status after oral phenibut ingestion intended to help self-manage opioid and benzodiazepine withdrawal. She chose self-directed detoxification as she feared COVID-19 exposure in detoxification facilities. Her altered mental status drove her to jump out a third-story window causing multiple spinal fractures. After a long hospitalization, she self-directed her discharge home due to concerns about COVID-19. Her premature discharge disrupted opioid and benzodiazepine use disorder treatment plans. CONCLUSION: This case highlights the risks of phenibut use for selfdirected detoxification. With COVID-19 related changes in the drug supply, people may be more likely to use online pharmaceuticals, therefore, substance use assessments should inquire about the online acquisition of new psychoactive drugs. Public health messaging regarding the risks of infectious disease transmission in addiction care settings is needed to guide addiction treatment choices among people who use substances.

Baclofen Withdrawal-Induced Psychosis in the Setting of Renal Insufficiency.

Baclofen is used to treat muscle spasticity, acting at GABA B receptors in the central nervous system. The abrupt cessation of baclofen causes baclofen withdrawal-induced psychosis. The risk is exacerbated if the patient has renal insufficiency or if the drug has been taken for a long time at high doses. Gradual tapering of baclofen usually does not produce symptomatic adverse effects. However, abrupt termination of the drug, especially in an inpatient hospital setting, can lead to symptoms such as increased spasticity, agitation, confusion, hallucinations, and seizures. We present a case of a patient who initially presented with seizures and experienced hallucinations after abrupt cessation of the medication. She had baseline chronic kidney disease but presented with acute worsening of her renal function. Impaired renal function decreases baclofen clearance and causes increased concentration of baclofen in circulation. This put the patient at higher risk of developing baclofen withdrawal, even at a lower dose.

Patterns of Alcohol Consumption Among Individuals With Alcohol Use Disorder During the COVID-19 Pandemic and Lockdowns in Germany.

Importance: Alcohol consumption (AC) leads to death and disability worldwide. Ongoing discussions on potential negative effects of the COVID-19 pandemic on AC need to be informed by real-world evidence. Objective: To examine whether lockdown measures are associated with AC and consumption-related temporal and psychological within-person mechanisms. Design, Setting, and Participants: This quantitative, intensive, longitudinal cohort study recruited 1743 participants from 3 sites from February 20, 2020, to February 28, 2021. Data were provided before and within the second lockdown of the COVID-19 pandemic in Germany: before lockdown (October 2 to November 1, 2020); light lockdown (November 2 to December 15, 2020); and hard lockdown (December 16, 2020, to February 28, 2021). Main Outcomes and Measures: Daily ratings of AC (main outcome) captured during 3 lockdown phases (main variable) and temporal (weekends and holidays) and psychological (social isolation and drinking intention) correlates. Results: Of the 1743 screened participants, 189 (119 [63.0%] male; median [IQR] age, 37 [27.5-52.0] years) with at least 2 alcohol use disorder (AUD) criteria according to the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) yet without the need for medically supervised alcohol withdrawal were included. These individuals provided 14 694 smartphone ratings from October 2020 through February 2021. Multilevel modeling revealed significantly higher AC (grams of alcohol per day) on weekend days vs weekdays (ß = 11.39; 95% CI, 10.00-12.77; P < .001). Alcohol consumption was above the overall average on Christmas (ß = 26.82; 95% CI, 21.87-31.77; P < .001) and New Year's Eve (ß = 66.88; 95% CI, 59.22-74.54; P < .001). During the hard lockdown, perceived social isolation was significantly higher (ß = 0.12; 95% CI, 0.06-0.15; P < .001), but AC was significantly lower (ß = -5.45; 95% CI, -8.00 to -2.90; P = .001). Independent of lockdown, intention to drink less alcohol was associated with lower AC (ß = -11.10; 95% CI, -13.63 to -8.58; P < .001). Notably, differences in AC between weekend and weekdays decreased both during the hard lockdown (ß = -6.14; 95% CI, -9.96 to -2.31; P = .002) and in participants with severe AUD (ß = -6.26; 95% CI, -10.18 to -2.34; P = .002). Conclusions and Relevance: This 5-month cohort study found no immediate negative associations of lockdown measures with overall AC. Rather, weekend-weekday and holiday AC patterns exceeded lockdown effects. Differences in AC between weekend days and weekdays evinced that weekend drinking cycles decreased as a function of AUD severity and lockdown measures, indicating a potential mechanism of losing and regaining control. This finding suggests that temporal patterns and drinking intention constitute promising targets for prevention and intervention, even in high-risk individuals.

Real-world study of multiple naloxone administration for opioid overdose reversal among bystanders.

BACKGROUND: The increasing prevalence of highly potent, illicitly manufactured fentanyl and its analogues (IMF) in the USA is exacerbating the opioid epidemic which has worsened during the COVID-19 pandemic. Narcan® (naloxone HCl) Nasal Spray has been approved by the US Food and Drug Administration as a treatment for opioid-related overdoses. Due to the high potency of IMF, multiple naloxone administrations (MNA) may be needed per overdose event. It is essential to determine the patterns of naloxone use, including MNA, and preferences among bystanders who have used naloxone for opioid overdose reversal. METHODS: A cross-sectional web-based survey was administered to 125 adult US residents who administered 4 mg Narcan® Nasal Spray during an opioid overdose in the past year. The survey asked about the most recent overdose event, the use of Narcan® during the event and the associated withdrawal symptoms, and participant preferences regarding dosages of naloxone nasal spray. An open-ended voice survey was completed by 35 participants. RESULTS: Participants were mostly female (70%) and white (78%), while reported overdose events most frequently occurred in people who were males (54%) and white (86%). Most events (95%) were successfully reversed, with 78% using ≥ 2 doses and 30% using ≥ 3 doses of Narcan® Nasal Spray. Over 90% were worried that 1 Narcan® box may not be enough for a successful future reversal. Reported withdrawal symptoms were similar in overdose events where 1 versus ≥ 2 sprays were given. Eighty-six percent of participants reported more confidence in an 8 mg versus a 4 mg naloxone nasal spray and 77% reported a stronger preference for 8 mg over 4 mg. CONCLUSIONS: MNA occurred in most overdose events, often involving more sprays than are provided in one Narcan® nasal spray box, and participants predominantly expressed having a stronger preference for and confidence in an 8 mg compared to a 4 mg nasal spray. This suggests the need and desire for a higher dose naloxone nasal spray formulation option. Given that bystanders may be the first to administer naloxone to someone experiencing an opioid overdose, ensuring access to an adequate naloxone supply is critical in addressing the opioid overdose epidemic.

Case 303: Delayed Posthypoxic Leukoencephalopathy.

HISTORY: A 54-year-old man was found by paramedics in his home face-down at his computer desk with a substantially reduced level of consciousness. He had not contacted his family for more than 50 hours. The patient lived alone and was a heavy smoker with a history of alcohol abuse. His medical history was otherwise unremarkable, and there was no history of cancer, psoriasis, or rheumatoid arthritis, nor was there a history of methotrexate administration. At presentation to the emergency department, he was mildly hypotensive and was experiencing hypercapnic respiratory failure and acute renal failure with rhabdomyolysis. His toxicology screen was mildly positive for opiates. He received naloxone (Narcan; Emergent) with minimal effect. An unenhanced CT scan of the head was obtained. Of note, this patient's presentation predated the COVID-19 pandemic. He was admitted to the intensive care unit for decreased level of consciousness and respiratory failure. The decreased level of consciousness was thought to be secondary to seizure, as he developed seizurelike movements prior to intubation, probably in the context of intoxication or alcohol withdrawal. Electroencephalography revealed moderate bilateral cerebral dysfunction and encephalopathy, with no evidence of nonconvulsive seizures. He had a short course of intermittent hemodialysis and was discharged home 8 days later with an appointment for neurology follow-up. At discharge, he was at his cognitive and functional baseline. Approximately 3 weeks later, the patient was brought back to the emergency department for progressive confusion and decrease in balance. He became apathetic with reduced psychomotor activity and was no longer able to perform basic daily activities, such as cooking or bathing. He displayed bizarre behavior, such as staring at a wall for hours, and was somnolent, irritable, and inattentive. He eventually became incontinent of urine and stool. Results of a neurologic examination of the cranial nerves, motor function, sensation, and reflexes were normal. The results of blood work-up were grossly normal, and the results of an extensive toxicology work-up were negative. Repeat head CT was performed. MRI was ordered to further investigate the patient's encephalopathic presentation.

The effect of the COVID-19 lockdown on mental health care use in South Africa: an interrupted time-series analysis.

AIMS: The coronavirus disease 2019 (COVID-19) pandemic and ensuing restrictions have negatively affected the mental health and well-being of the general population, and there is increasing evidence suggesting that lockdowns have led to a disruption of health services. In March 2020, South Africa introduced a lockdown in response to the COVID-19 pandemic, entailing the suspension of all non-essential activities and a complete ban of tobacco and alcohol sales. We studied the effect of the lockdown on mental health care utilisation rates in private-sector care in South Africa. METHODS: We conducted an interrupted time-series analysis using insurance claims from 1 January 2017 to 1 June 2020 of beneficiaries 18 years or older from a large private sector medical insurance scheme. We calculated weekly outpatient consultation and hospital admission rates for organic mental disorders, substance use disorders, serious mental disorders, depression, anxiety, other mental disorders, any mental disorder and alcohol withdrawal syndrome. We calculated adjusted odds ratios (OR) for the effect of the lockdown on weekly outpatient consultation and hospital admission rates and the weekly change in rates during the lockdown until 1 June 2020. RESULTS: 710 367 persons were followed up for a median of 153 weeks. Hospital admission rates (OR 0.38; 95% confidence interval (CI) 0.33-0.44) and outpatient consultation rates (OR 0.74; 95% CI 0.63-0.87) for any mental disorder decreased substantially after the introduction of the lockdown and did not recover to pre-lockdown levels by 1 June 2020. Health care utilisation rates for alcohol withdrawal syndrome doubled after the introduction of the lockdown, but the statistical uncertainty around the estimates was large (OR 2.24; 95% CI 0.69-7.24). CONCLUSIONS: Mental health care utilisation rates for inpatient and outpatient services decreased substantially after the introduction of the lockdown. Hospital admissions and outpatient consultations for alcohol withdrawal syndrome increased after the introduction of the lockdown, but statistical uncertainty precludes strong conclusions about a potential unintended effect of the alcohol sales ban. Governments should integrate strategies for ensuring access and continuity of essential mental health services during lockdowns in pandemic preparedness planning.

Efficacy of tiapride in the treatment of psychiatric disorders: A systematic review.

BACKGROUND: Tiapride is an atypical antipsychotic used to treat alcohol withdrawal, aggressiveness and agitation, headache, dyskinesias, tic and Tourette's disorder. More recently, it has been proposed for the treatment of delirium and agitation in hospitalised patients with COVID-19. Although its safety profile makes it suitable for use in vulnerable populations, the use of tiapride for psychiatric disorders is limited. This work aims to systematically review the available evidence on the efficacy and tolerability of tiapride in individuals with a psychiatric disorder. METHODS: We searched PubMed, Embase, PsycINFO, GreyLit, OpenGrey, and ProQuest up to March 2020 for randomised controlled trials focussing on the use of tiapride in the treatment of individuals with a psychiatric disorder (e.g., mood disorder, schizophrenia spectrum, substance use disorder). The Risk of Bias 2 was performed for the quality assessment of the included studies. RESULTS: We identified 579 records. Of them, six studies (published between 1982 and 2010) were included in the review. Four studies referred to alcohol withdrawal, and two to the management of agitation in elderly patients with dementia. None of the studies reported significant differences between tiapride and other active comparators in terms of efficacy and tolerability. The overall risk of bias was moderate to high. CONCLUSION: Tiapride may be considered as a relatively safe treatment option for selected patients with alcohol withdrawal or agitation in dementia. However, solid evidence of its efficacy in the scientific literature is lacking. High-quality trials remain necessary to fully sustain its use in clinical practice.

"I got a bunch of weed to help me through the withdrawals": Naturalistic cannabis use reported in online opioid and opioid recovery community discussion forums.

A growing body of research has reported on the potential opioid-sparing effects of cannabis and cannabinoids, but less is known about specific mechanisms. The present research examines cannabis-related posts in two large online communities on the Reddit platform ("subreddits") to compare mentions of naturalistic cannabis use by persons self-identifying as actively using opioids versus persons in recovery. We extracted all posts mentioning cannabis-related keywords (e.g., "weed", "cannabis", "marijuana") from December 2015 through August 2019 from an opioid use subreddit and an opioid recovery subreddit. To investigate how cannabis is discussed at-scale, we identified and compared the most frequent phrases in cannabis-related posts in each subreddit using term-frequency-inverse document frequency (TF-IDF) weighting. To contextualize these findings, we also conducted a qualitative content analysis of 200 random posts (100 from each subreddit). Cannabis-related posts were about twice as prevalent in the recovery subreddit (n = 908; 5.4% of 16,791 posts) than in the active opioid use subreddit (n = 4,224; 2.6% of 159,994 posts, p < .001). The most frequent phrases from the recovery subreddit referred to time without using opioids and the possibility of using cannabis as a "treatment." The most frequent phrases from the opioid subreddit referred to concurrent use of cannabis and opioids. The most common motivations for using cannabis were to manage opioid withdrawal symptoms in the recovery subreddit, often in conjunction with anti-anxiety and GI-distress "comfort meds," and to enhance the "high" when used in combination with opioids in the opioid subreddit. Despite limitations in generalizability from pseudonymous online posts, this examination of reports of naturalistic cannabis use in relation to opioid use identified withdrawal symptom management as a common motivation. Future research is warranted with more structured assessments that examines the role of cannabis and cannabinoids in addressing both somatic and affective symptoms of opioid withdrawal.

Managed alcohol: one community's innovative response to risk management during COVID-19.

BACKGROUND: Harm reduction programs often lack community-based support and can be controversial, despite data demonstrating effectiveness. This article describes one small Alaskan community's development of a harm reduction managed alcohol program (MAP) in the context of a city-run quarantine site for individuals experiencing homelessness. The MAP was developed to support quarantining by COVID-19-exposed or COVID-positive individuals who also experienced chronic homelessness, a severe alcohol use disorder, and heightened health risks related to potentially unsupported alcohol withdrawal. METHOD: Five interviews with key informants involved in planning or implementation of the MAP were conducted using rapid qualitative analysis and narrative analysis techniques. OUTCOME: This study documents the planning and implementation of an innovative application of a managed alcohol harm reduction intervention in the context of the COVID-19 pandemic. In this instance, a MAP was used specifically to limit hospital admissions for alcohol withdrawal during a surge of cases in the community, as well as to mitigate spread of the virus. Key informants report no residents enrolled in the MAP program as a part of quarantine required hospitalization for withdrawal or for COVID symptoms, and no shelter resident left the quarantine site while still contagious with COVID-19. Additionally, the level of community support for the program was much higher than originally expected by organizers. CONCLUSIONS: This program highlighted an example of how a community recognized the complexity and potential risk to individuals experiencing structural vulnerability related to homelessness and a severe AUD, and the community at large, and was able to create an alternative path to minimize those risks using a harm reduction strategy.

Prevention of alcohol withdrawal seizure recurrence and treatment of other alcohol withdrawal symptoms in the emergency department: a rapid review.

BACKGROUND: Patients who experience harms from alcohol and other substance use often seek care in the emergency department (ED). ED visits related to alcohol withdrawal have increased across the world during the COVID-19 pandemic. ED clinicians are responsible for risk-stratifying patients under time and resource constraints and must reliably identify those who are safe for outpatient management versus those who require more intensive levels of care. Published guidelines for alcohol withdrawal are largely limited to the primary care and outpatient settings, and do not provide specific guidance for ED use. The purpose of this review was to synthesize published evidence on the treatment of alcohol withdrawal syndrome in the ED. METHODS: We conducted a rapid review by searching MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials (1980 to 2020). We searched for grey literature on Google and hand-searched the conference abstracts of relevant addiction medicine and emergency medicine professional associations (2015 to 2020). We included interventional and observational studies that reported outcomes of clinical interventions aimed at treating alcohol withdrawal syndrome in adults in the ED. RESULTS: We identified 13 studies that met inclusion criteria for our review (7 randomized controlled trials and 6 observational studies). Most studies were at high/serious risk of bias. We divided studies based on intervention and summarized evidence narratively. Benzodiazepines decrease alcohol withdrawal seizure recurrence and treat other alcohol withdrawal symptoms, but no clear evidence supports the use of one benzodiazepine over another. It is unclear if symptom-triggered benzodiazepine protocols are effective for use in the ED. More evidence is needed to determine if phenobarbital, with or without benzodiazepines, can be used safely and effectively to treat alcohol withdrawal in the ED. Phenytoin does not have evidence of effectiveness at preventing withdrawal seizures in the ED. CONCLUSIONS: Few studies have evaluated the safety and efficacy of pharmacotherapies for alcohol withdrawal specifically in the ED setting. Benzodiazepines are the most evidence-based treatment for alcohol withdrawal in the ED. Pharmacotherapies that have demonstrated benefit for treatment of alcohol withdrawal in other inpatient and outpatient settings should be evaluated in the ED setting before routine use.

Cognitive Behavioral Therapy and Acceptance and Commitment Therapy for the Discontinuation of Long-Term Benzodiazepine Use in Insomnia and Anxiety Disorders.

Benzodiazepines have proven to be highly effective for treating insomnia and anxiety. Although considered safe when taken for a short period of time, a major risk-benefit dilemma arises in the context of long-term use, relating to addiction, withdrawal symptoms, and potential side effects. For these reasons, benzodiazepines are not recommended for treating chronic sleep disorders, anxiety disorders, nor for people over the age of 65, and withdrawal among long-term users is a public health issue. Indeed, only 5% of patients manage to discontinue using these drugs on their own. Even with the help of a general practitioner, this rate does not exceed 25 to 30% of patients, of which approximately 7% manage to remain drug-free in the long term. Cognitive Behavioral Therapies (CBT) offer a crucial solution to this problem, having been shown to increase abstinence success to 70-80%. This article examines traditional and novel CBT techniques in this regard, such as Acceptance and Commitment Therapy, which address both the underlying condition (insomnia/anxiety) and the substance-related disorder. The theoretical framework and evidence supporting the use of these approaches are reviewed. Finally, current research gaps are discussed, and key research perspectives are proposed.

Weaning Analgosedation in Patients Requiring Prolonged Mechanical Ventilation.

Although research supports the minimization of sedation in mechanically ventilated patients, many patients with severe acute respiratory distress syndrome (ARDS) receive prolonged opioid and sedative infusions. ICU teams face the challenge of weaning these medications, balancing the risks of sedation with the potential to precipitate withdrawal symptoms. In this article, we use a clinical case to discuss our approach to weaning analgosedation in patients recovering from long-term mechanical ventilation. We believe that a protocolized, multimodal weaning strategy implemented by a multidisciplinary care team is required to reduce potential harm from both under- and over-sedation. At present, there is no strong randomized clinical trial evidence to support a particular weaning strategy in adult ICU patients, but appraisal of the existing literature in adults and children can guide decision-making to enhance the recovery of these patients.

Influence of Pennsylvania liquor store closures during the COVID-19 pandemic on alcohol withdrawal consultations.

INTRODUCTION: Alcohol withdrawal syndrome (AWS) is a serious consequence of alcohol use disorder (AUD). Due to the current COVID-19 pandemic there was a closure of Pennsylvania (PA) liquor stores on March 17, 2020. METHODS: This is a retrospective, observational study of AWS patients presenting to a tertiary care hospital. We used descriptive statistics for continuous and categorical variables and compared AWS consults placed to the medical toxicology service for six months preceding liquor store closure to those placed between March 17, 2020 and August 31, 2020. We compared this to consults placed to the medical toxicology service placed from October 1, 2019 through March 16, 2020. Charts were identified based on consults placed to the medical toxicology service, and alcohol withdrawal was determined via chart review by a medical toxicologist. This study did not require IRB approval. We evaluated Emergency Department (ED) length of stay (LOS), weekly and monthly consultation rate, rate of admission and ED recidivism, both pre- and post-liquor store closure. RESULTS: A total of 324 AWS consults were placed during the ten month period. 142 (43.8%) and 182 (56.2%) consults were pre- and post-liquor store closure. The number of consults was not statistically significant comparing these two time frames. There was no significant difference by patient age, gender, or race or by weekly or monthly consultation rate when comparing pre- and post-liquor store periods. The median ED LOS was 7 h (95% Confidence Interval (CI) Larson et al. (2012), Pollard et al. (2020) [5, 11]) and did not significantly differ between pre- and post-liquor store periods (p = 0.78). 92.9% of AWS patients required admission without significant difference between the pre- and post-liquor store closure periods (94.4% vs. 91.8%, p = 0.36). There was a significant increase in the number of AWS patients requiring a return ED visit (Odds Ratio 2.49; 95% CI [1.38, 4.49]) post closure. CONCLUSION: There were nearly 2.5 times greater odds of ED recidivism among post-liquor store closure AWS patients compared with pre-closure AWS patients.

The Pharmacology of Buprenorphine Microinduction for Opioid Use Disorder.

Although expanding the availability of buprenorphine-a first-line pharmacotherapy for opioid-use disorder (OUD)-has increased the capacity of healthcare systems to offer treatment, starting this medication is fraught with significant barriers. Standard induction regimens require persons with OUD to taper and discontinue full opioid agonists and experience opioid withdrawal prior to the first dose of buprenorphine. Further, emerging evidence indicates that precipitated withdrawal during induction may impact long-term treatment outcomes. Microinduction is a novel approach that, by harnessing buprenorphine's unique pharmacological profile, may allow circumventing the needed for prolonged opioid tapers, and reduce the risk of precipitated withdrawal-holding promise to enhance treatment access. In this review, we examine the pharmacological basis for microinduction and appraise the evidence of this approach to improve clinical outcomes among persons with OUD. First, we highlight the potential dose-dependent effects of buprenorphine on two key neuroadaptations at the mu-opioid receptor (MOR)-resensitization and upregulation. We then focus on how microinduction may reverse these chronic MOR neuroadaptations, allowing the maintenance of an adequate opioid tone, and thereby potentially circumventing opioid withdrawal. Second, we describe the clinical evidence available, derived from observational reports and open-label studies, examining the potential efficacy of microinduction. Despite significant heterogeneity-exemplified by variable buprenorphine formulations, daily doses, and schedules of administration-these data provide preliminary support for the feasibility of microinduction. Finally, we provide new mechanistic, methodological, and clinical insights to guide future translational research, as well as randomized, placebo-controlled clinical trials in this compelling agenda of pharmacotherapy development.