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Introduction An ED visit for opioid overdose may be a person's only contact with the medical and behavioral health care systems and is an important opportunity to reduce risk of subsequent overdose and death. While ED initiatives to engage people with opioid use disorder (OUD) are being increasingly implemented, there are significant gaps in the receipt of services at the time of the ED encounter. Methods This is a retrospective cohort study of an outreach pilot project providing real-time telehealth delivered buprenorphine initiation and referral to community harm reduction and addiction treatment services via a follow up telephone call to patients after an ED visit for an opioid overdose. Results From January 2020 to April 2021 there were 606 patients with an ED visit for an opioid overdose eligible for a callback. Of the 606 eligible patients, 254/645 (42%) patients could be contacted and accepted service and/or treatment referrals. Fifteen patients were connected same-day to a buprenorphine prescriber for a telehealth encounter and, of connected patients, nine received a buprenorphine prescription. Conclusion A post-ED follow up telephone call protocol is an opportunity to improve treatment engagement and access to buprenorphine for patients at high risk for opioid overdose and death.

STUDY OBJECTIVE Emergency department (ED)-based naloxone distribution and peer-based behavioral counseling have been shown to be feasible, but little is known about utilization maintenance over time and clinician, patient, and visit level factors influencing implementation. METHODS We conducted a retrospective cohort study of an ED overdose prevention program providing take-home naloxone, behavioral counseling, and treatment linkage for patients treated for an opioid overdose at two Rhode Island EDs from 2017 to 2020: one tertiary referral center and a community hospital. Utilizing a Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework, we evaluated program reach, adoption, implementation modifiers, and maintenance using logistic and Poisson regression. RESULTS Seven hundred forty two patients were discharged after an opioid overdose, comprising 966 visits (median: 32 visits per month; interquartile range: 29, 41). At least one intervention was provided at most (86%, 826/966) visits. Take-home naloxone was provided at 69% of visits (637/919). Over half (51%, 495/966) received behavioral counseling and treatment referral (65%, 609/932). Almost all attending physicians provided take-home naloxone (97%, 105/108), behavioral counseling (95%, 103/108), or treatment referral (95%, 103/108) at least once. Most residents and advanced practice practitioners (APPs) provided take home naloxone (78% residents; 72% APPs), behavioral counseling (76% residents; 67% APPs), and treatment referral (80% residents; 81% APPs) at least once. Most clinicians provided these services for over half of the opioid overdose patients they cared for. Patients were twice as likely to receive behavioral counseling when treated by an attending in combination with a resident and/or APP (adjusted odds ratio: 2.29; 95% confidence interval, 1.68, 3.12) compared to an attending alone. There was no depreciation in use over time. CONCLUSIONS ED naloxone distribution, behavioral counseling, and referral to treatment can be successfully integrated into usual emergency care and maintained over time with high reach and adoption. Further work is needed to identify low-cost implementation strategies to improve services use and dissemination across clinical settings.

Background: Ratios of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) impact metabolism and therapeutic effects of cannabis. Currently, no states with legalized medical or recreational cannabis consider ratios THC:CBD in regulations. Objective: Determine what THC:CBD ratios are selected for use in clinical cannabis trials and what is the rationale. Methods: This is a systematic literature review of Central, CINAHL, Embase, PsycInfo, and PubMed of the last 10 years of English language medical cannabis publications highlighting THC:CBD ratios. Included were clinical studies of products containing and listing both THC and CBD ratios, percentages, or weighted amounts. Case reports and series, abstracts, reviews, and meta-analysis were excluded. Non-human, non-therapeutic, or studies examining approved cannabis pharmaceuticals were excluded. Results: Four hundred and seventy-nine (479) unique references were found, of which 11 met inclusion criteria. THC:CBD ratios listed and/or calculated: 1:0, 22:1, 2:1, 1:1, 1:2, 1:6, 1:9, 1:20, 1:33, 1:50, and 0:1. Rationale for ratios selected was often not listed, or simply trivialized as the ratios available to patients in the area, or ratios that were pharmaceutically available throughout the study country. One study compared ratios of high and low THC:CBD, but did not specify the ratios. Conclusion: The medical and scientific communities have not drawn substantive conclusions nor thoroughly explored THC:CBD ratios for "best practice" treatment of different disease processes and their sequelae. While there is evidence that cannabis provides medical benefits, research is lacking on standardization of medical cannabis use in modern medical practices.

Background Precipitated opioid withdrawal (POW) after opioid antagonist administration can be challenging to manage in the emergency department (ED), particularly if caused by a long-acting opioid antagonist such as naltrexone. There are no evidence-based guidelines to assist in safely and efficiently managing patients with this syndrome. Objective of Review To review current practice on the treatment of long-acting antagonist POW and make recommendations on the treatment of this complex disease process. Methods A literature search of opioid withdrawal cases precipitated by naltrexone was done using PubMed. One of the authors screened all the results of this search by title and abstract, leading to a final count of 27 articles that were reviewed in full by all authors. English language cases that involved precipitated opioid withdrawal from a long-acting opioid antagonist were included. Data were extracted, including the precipitant involved and dose, severity of opioid withdrawal, treatments rendered, and response to treatment. In all cases where symptoms and signs were described, a Clinical Opiate Withdrawal Scale score was calculated based on the information available. Results Twenty-seven papers were included. Naltrexone alone was the primary antagonist reported in 19 of the papers, extended-release naltrexone in two, naltrexone-morphine combination in two, and nalmefene in four. Treatment most commonly included fluid replacement, benzodiazepines, antiemetics, and clonidine. Full opioid agonist treatment, although often suggested, was poorly described. Buprenorphine successfully reduced the severity and duration of withdrawal in several cases. No standardized response scale was used, and response to treatment ranged from 3 to 48 h prior to resolution of clinical effects. Conclusions Management of POW from long-acting antagonists is a complex problem with little formal evaluation of treatment options. There is not currently a sufficiently robust body of literature to support an evidence-based guideline. However, use of intravenous fluids, antiemetics, and benzodiazepines is commonly reported as successful and seems to be a reasonable approach until this process is better studied. A treatment strategy using partial agonists such as buprenorphine is emerging and may represent a safe and effective treatment pathway for these patients.

In July 2020, the Massachusetts Drug Supply Data Stream (MADDS) encountered two drug samples sold in a community as cocaine (one as “crack” and one as “white rock”) that contained bupropion as the ...

Background Emergency departments (EDs) in the US have increasingly incorporated interventions that seek to reduce opioid-related morbidity and mortality. However, many of these interventions are underutilized. This study examined ED provider-identified barriers and facilitators to policy-prescribed service provision for patients treated for an opioid overdose in Rhode Island EDs, and opportunities to improve care delivery. Methods Semi-structured qualitative interviews were conducted with 55 ED providers (management and clinical staff) across Rhode Island EDs from November 2019 to July 2020. Thematic analysis of interviews focused on gaps and best practices in post-overdose care delivery, including social and structural factors driving access to, and uptake of, services. Results Participants highlighted how automatic service delivery (opt out vs. opt in) and the integration of peer-based services enhanced post-overdose service provision. However, social and structural factors (e.g. insurance barriers, limited outpatient treatment resources) and gaps in provider knowledge of medications for opioid use disorder created barriers to care. Addressing long ED wait times and establishing dedicated care teams for patients following an overdose were seen as critical to improving ED service delivery. Conclusion Our findings suggest that post-overdose service delivery within EDs is a useful approach for connecting patients to services, particularly when peer support specialists are involved. However, standardizing service delivery approaches and improving provider education of harm reduction services must be prioritized alongside state-level policy changes to improve access to care for ED patients.

Despite its proven efficacy, buprenorphine remains dramatically underutilized for management of opioid use disorder largely due to onerous barriers to treatment initiation. During the COVID-19 pandemic, many substance use disorder treatment facilities have reduced their hours and services, exacerbating existing barriers. To this end, the U.S. Drug Enforcement Administration and Substance Abuse Mental Health Services Administration adjusted their guidelines to allow for new buprenorphine prescriptions following audio-only telehealth encounters, no longer requiring an in-person evaluation prior to treatment initiation. Under this new guidance, we established a 24/7 telephone hotline to function as a “tele-bridge” clinic where people with opioid use disorder can be linked with a buprenorphine prescriber in real-time for OUD assessment and unobserved buprenorphine initiation with connection to follow-up if appropriate. Additionally, we developed an ED callback protocol to reach patients recently seen for opioid overdose and facilitate their entry into care if interested. In this commentary we describe our hotline and ED callback protocols, discuss theoretical and anecdotal benefits to this approach, and advocate for continuation of current regulatory changes post-COVID-19 to maintain expanded access to novel treatment approaches., Highlights • Despite buprenorphine’s efficacy it remains underutilized, amplified by COVID-19 • Underutilization of buprenorphine is largely due to barriers to treatment entry • Novel telehealth initiatives provide an opportunity to minimize these barriers • New initiatives are well received and need to be continued to evaluate efficacy

Background To minimize the spread of COVID-19, health and ancillary care providers altered service delivery patterns. These changes included an increase in reliance on telemedicine modalities, a reduction in services or hours of operation, and prohibiting guests and nonessential personnel from healthcare settings. We describe a rapid environmental assessment with senior emergency department (ED) practitioners in Rhode Island to understand how COVID-related procedural changes impact the provision of post-overdose care in ED. Methods Semi-structured interviews were conducted with 14 senior healthcare practitioners in EDs across Rhode Island from June to July 2020. Interviews were part of a larger, ongoing study examining the implementation and effectiveness of post-opioid overdose care in EDs and sought to understand how COVID-19 had impacted the provision of services for people who use drugs (PWUD). Results COVID-related policy changes challenged the provision of services to PWUD in the ED, and extended challenges in connecting people with OUD to services in the community. Specifically, challenges included transitions to telehealth modalities, required COVID tests for treatment services, and gaps in community resources. Conclusions This study underscores opportunities to improve the delivery of services amid overlapping public health crises for PWUD, including bolstering the use of telemedicine in EDs and across the care continuum.

Introduction Patients with substance use disorder may be particularly vulnerable to withdrawal-related complications during the SARS-CoV-2 (COVID-19) pandemic. Limited availability of alcohol and other substances coupled with decreased accessibility to substance use treatment poses a substantial risk to this population. Isopropanol, the active ingredient in rubbing alcohol, is widely available; thus, it may be used in times of scarcity. Case report We present a case of intentional isopropanol ingestion used as an ethanol surrogate within the setting of the COVID-19 pandemic. Conclusions Toxic alcohol ingestions are imperative considerations on the differential for the intoxicated patient particularly during resource-limited times.

BACKGROUND: Buprenorphine is a unique μ-opioid receptor partial agonist with avid receptor binding, nominal euphoric reward, and a ceiling effect on sedation and respiratory depression. Despite a pharmacologic profile that enhances safety, cases of fatal opioid overdose with buprenorphine on postmortem toxicology are reported, but details of these cases in the literature are limited. METHODS: A retrospective review of opioid-involved drug overdose fatalities in Rhode Island (RI) from 2016 to 2018 using the RI Department of Health State Unintentional Drug Overdose Reporting System (SUDORS) database. Deaths with buprenorphine on toxicology testing versus opioid-involved overdose deaths without buprenorphine were compared to assess the type and number of co-exposures. RESULTS: Of 534 opioid-involved deaths, 29 (5.4%) included buprenorphine and/or norbuprenorphine on toxicology. Most frequent co-exposures are as follows: fentanyl (75.9%), norfentanyl (72.4%), cocaine (41.4%), benzoylecgonine (41.4%), cannabinoids (31.0%), ethanol (31.0%), levamisole (31.0%), and free morphine (31.0%). An average number of co-exposures for fatalities with buprenorphine were 9.24 versus 6.68 in those without buprenorphine. In one case buprenorphine was the only drug listed to cause death; all other fatalities with buprenorphine on toxicology reported additional drugs contributing to death. CONCLUSION: Decedents with buprenorphine detected on toxicology testing commonly had documented polysubstance use. Although data are limited, buprenorphine may provide some risk mitigation against full agonist opioid overdose including fentanyl. Further work should explore the use of postmortem concentrations of buprenorphine, norbuprenorphine, and other opioid metabolites to determine the role of buprenorphine in fatal overdose pharmacology.

During the COVID-19 pandemic, many addiction treatment and harm reduction organizations have had to reduce their hours and services for people with substance use disorders, placing these individuals at increased risk of death. In order to address restricted treatment access during COVID-19, guidance from the Substance Abuse Mental Health Services Administration, the US Drug Enforcement Administration, and the US Department of Health and Human Services has allowed for use of audio-only telehealth encounters for buprenorphine induction without requiring an in-person evaluation or video interface. This has enabled innovations in order to try to meet the needs of the most vulnerable among us during the current pandemic. In this new regulatory environment, we established the Rhode Island Buprenorphine Hotline, a phone hotline which functions as a "tele-bridge" clinic where people with moderate to severe opioid use disorder can be linked with a DATA 2000 waivered provider who can provide an initial assessment and, if appropriate, prescribe buprenorphine for unobserved induction and linkage to outpatient treatment. In this correspondence we briefly share our experience developing this common sense approach to addressing the complex problem of access to treatment only now permissible due to regulatory changes during COVID-19.

Brexanolone recently became the first medication to be approved by the US Food and Drug Administration specifically for treating postpartum depression. In contrast to traditional antidepressants, however, brexanolone is a neurosteroid that is believed to mimic allopregnanolone, a product of endogenous progesterone. Although early clinical trials have shown success, the medication remains largely unavailable due to its extremely high cost and formulation (it must be given as a continuous intravenous infusion over 3 days in a monitored, inpatient setting). The efficacy data surrounding brexanolone are encouraging; there is also evidence, however, that postpartum depression may be mitigated by a number of social policies that provide support to new parents. We suggest a comprehensive approach to postpartum wellness that includes investing in evidence-based social interventions that may be much more accessible to the millions of Americans experiencing postpartum mood disturbance.

Many individuals who use opioids turn to online resources to gather information on effects, availability, and safety.Describe opioid index page views on Erowid.org to assess trends in public interest in particular opioids.Retrospective analysis of Erowid.org site traffic was performed to identify unique average daily visits to opioid pages. All data was normalized to that of visits to the heroin index page. Average daily visits to the index pages of each of 6 commonly abused opioids were assessed during the period of 2009 to 2015. Similarly, visits to 15 distinct opioid index pages at 5 time points (July, October 2014 and Jan, April, and July 2015) were described.From 2009 to 2015 a decrease in the number of page visits versus heroin (1.00) occurred for hydrocodone (0.87 to 0.59, -32%), oxycodone (1.38 to 0.99, -28%), and morphine (0.26 to 0.25, -6%). Increases in page visits compared to heroin occurred for fentanyl (0.18 to 0.47, +157%), tramadol (0.43 to 0.88, +106%), hydromorphone (0.19 to 0.24, +29%), and oxymorphone (0.11 to 0.13, +18%). Indexed to heroin (1.00) average opioid page visit frequencies from July 2014 to July 2015 were highest for oxycodone (1.02) and tramadol (0.81). Conclusion/Importance: Oxycodone and tramadol represent the greatest number of Erowid.org opioid page visits compared to heroin. The largest increase in visits over the study periods was for fentanyl and tramadol. The relationship of page visits on Erowid.org creates a unique opportunity for real-time evaluation of emerging drug trends and epidemiological study.

Nonmedical use of prescription opioid analgesics is associated with epidemic levels of morbidity and mortality. There are several factors that affect the abuse liability of the various opioids, including likability or the pleasurable subjective effects. Due to rising public health concerns over escalating prescription opioid abuse, we sought to examine the literature about abuse liability with a specific focus on likability studies.A search of EMBASE and MEDLINE databases identified articles that described the comparative likeability and/or abuse potential of hydrocodone and oxycodone relative to each other and/or of either one to morphine. After an assessment of study quality using the Oxford/Jadad scale, relevant details such as demographics, study design, and outcome measures were compiled into an evidence table.We identified nine studies that met inclusion criteria. All were double-blinded, randomized, placebo-controlled crossover studies and scored 5 out of 5 Jadad scale. There was no consistent clinically significant difference between abuse liability of morphine and hydrocodone. Oxycodone demonstrated high abuse liability on the basis of its high likability scores and a relative lack of negative subjective effects.Oral oxycodone has an elevated abuse liability profile compared to oral morphine and hydrocodone.

Loperamide is an over-the-counter antidiarrheal with opioid-receptor agonist properties. Recommended over-the-counter doses (range = 2-8 mg daily) do not produce opioid effects in the central nervous system because of poor oral bioavailability and P-glycoprotein efflux* of the medication (1); recent reports suggest that large doses (50-300 mg) of loperamide produce euphoria, central nervous system depression, and cardiotoxicity (2-4). Abuse of loperamide for its euphoric effect or for self-treatment of opioid withdrawal is increasing (5). Cases of loperamide abuse reported to the Upstate New York Poison Center and New York City Poison Control Center were analyzed for demographic, exposure, clinical, and laboratory characteristics. Cases of intentional loperamide abuse reported to the National Poison Database System (NPDS) also were analyzed for demographic, dose, formulation, and outcome information.

Loperamide, a non-prescription anti-diarrheal agent, is a peripheral mu-opioid receptor agonist that is excluded from the blood-brain barrier by p-glycoprotein at therapeutic doses. Overdoses of loperamide penetrate the central nervous system (CNS), leading to abuse. We report cardiac conduction abnormalities and dysrhythmias after ingestion of a recreational supra-therapeutic dose of loperamide confirmed with an elevated blood loperamide concentration.A 48-year-old woman with a history of alcohol and benzodiazepine abuse presented to the emergency department (ED) with somnolence, weakness and slurred speech. She was taking 20 to 40 tablets of 2 mg loperamide 1-2 times/day for weeks along with clonazepam and whiskey. Vital signs were: blood pressure (BP), 124/90 mmHg; heart rate (HR), 88/min; respiratory rate(RR), 20/min; T, 36.9 °C; O2 saturation 100% on room air (RA). Glucose was 6.4 mmol/L. Electrocardiogram (ECG) had a ventricular rate of 58/min, QRS 164 ms, QT 582 ms with no discernable p-waves. Lactate was 3.5 mmol/L and potassium was 6.2 mEq/L. Labs were notable for an anion gap of 20 mEq/L, ethanol of 3.9 mmol/L, creatinine of 2.3 mg/dL and loperamide concentration of 210 ng/mL (average therapeutic plasma concentration 1.2 ng/mL). She became hypotensive, but responded to fluids. Following treatment for hyperkalemia with calcium, insulin, dextrose, and hypertonic sodium bicarbonate a repeat ECG had a ventricular rate of 66/min, QRS 156 ms, and QT 576 ms. Magnesium was given and pacer pads were placed. During the infusion of magnesium, her BP fell to 92/58 mmHg with a HR of 54/min, RR 14/min, O2 saturation of 97% on RA so the infusion was stopped. The ECG after the magnesium infusion had a ventricular rate of 51/min, QRS of 134 ms, and QT 614 ms. In the ICU she had multiple runs of non-sustained ventricular tachycardia that did not require therapy. Over the next 48 h she improved and was transferred to a floor bed. On day four of hospitalization the patient left against medical advice. At that time, her ECG showed sinus tachycardia with a heart rate 114/min, QRS 82 ms, QT 334 ms.Loperamide produces both QRS and QT prolongation at supra-therapeutic dosing. A blood loperamide concentration of 210 ng/mL is among the highest concentrations reported. Supra-therapeutic dosing of loperamide is promoted on multiple drug-use websites and online forums as a treatment for opioid withdrawal, as well as for euphoric effects. With the current epidemic of prescription opioid abuse, toxicity related to loperamide, an opioid agonist that is readily available without a prescription is occurring more frequently. It is important for clinicians to be aware of the potentially life-threatening toxicity related to loperamide abuse in order to provide proper diagnosis, management and patient education.

The risk of severe precipitated opioid withdrawal (POW) is amplified when precipitated by a long-acting opioid antagonist. IM extended release naltrexone (XRNTX;Vivitrol®) is an FDA approved therapy to prevent relapse of opioid and alcohol abuse. Two cases of precipitated opioid withdrawal from XRNTX are presented that illustrate different patient reactions to POW. A 56-year-old woman developed a hypertensive emergency and required continuous intravenous vasodilator, clonidine, and intensive care monitoring after re-initiation of XRNTX following opioid relapse. A 25-year-old man developed agitation and altered mental status after receipt of XRNTX at the conclusion of a twelve-day detoxification program during which he continued surreptitious use of heroin. The patient received benzodiazepines and haloperidol without adequate affect, and required intubation with propofol, lorazepam, and dexmedetomidine infusions. Management of POW from XRNTX is a challenge to emergency providers and protocols to guide management do not exist. Recommended therapies include intravenous fluids, anti-emetics, clonidine, or benzodiazepines as well as therapy tailored to the organ system affected. To minimize risk of POW it is important for providers instituting XRNTX to adhere to the manufacturers warnings and clinic protocols including a naloxone challenge and ensure an adequate opioid free period prior to administration of XRNTX.

The purpose of this study was to investigate the diagnostic yield and safety of electromagnetic navigation bronchoscopy (ENB) on peripheral lung lesions deemed otherwise unreachable using conventional bronchoscopy in high-risk patients.This was a retrospective chart review involving adults (age, 18 y and older) who underwent ENB for pulmonary lesions located at the fourth order of bronchi or beyond, including subpleural lesions, at the University of Chicago Medical Center. Forty-eight patients underwent ENB by 3 different trained operators from January 2006 to September 2008. There was a short period of inactivity when the device was withdrawn from the market. ENB was reserved for use only in lesions at the fourth order of bronchi or beyond, including subpleural lesions, in patients who are considered high risk for other invasive procedures. Pathologic, cytologic, and microbiologic studies were carried out on recovered samples. Postprocedural chest radiographs were obtained on all patients to detect the presence of procedure-associated complications.ENB led to the diagnosis of 37 of 48 (77%) lesions not amenable to conventional bronchoscopic biopsy in high-risk patients. Of the 37 successful procedures, malignancy was identified in 18 patients (49%). Nonsmall cell lung cancer (NSCLC) was diagnosed 16 times, whereas both small cell lung cancer and carcinoid tumor were diagnosed once. In addition, 4 lesions (11%) were found to be infectious, 1 lesion (3%) was found to be granulomatous (noncaseating), and 1 lesion (3%) was diagnosed as organizing pneumonia. Of the 37 successful diagnoses, 13 lesions (35%) were determined to be nonpathologic, benign lesions. Eleven procedures (22%) were unsuccessful in yielding the correct pathologic diagnosis. Nine of the 11 unsuccessful ENB cases (82%) were found to be malignant, 9 of which were identified as NSCLC. Other than NSCLC, 1 neuroendocrine tumor (9%) and 1 metastatic transitional cell carcinoma of the kidney (9%) were identified by alternative, invasive testing methods. The 2 other lesions unsuccessfully diagnosed by ENB were not malignant. One was determined to be infection (histoplasmosis) and the other was diagnosed as an organizing pneumonia. The most common complication noted by all modalities was pneumothorax. ENB carried a pneumothorax rate of 5 of 49 (10%), 2 of which required chest tube insertion for treatment. In the ENB success group, 4 cases (11%) were complicated by pneumothoraces. In the ENB failure group, 1 case (9%) was complicated by a pneumothorax.ENB is an effective and low-risk modality for diagnosing pulmonary lesions that are difficult to reach in patients deemed to be at high risk for invasive procedures. Although no clear criteria for the use of ENB currently exist, our study shows that diagnostic sampling can be obtained in 77% of lesions at the fourth order of bronchi or beyond, including subpleural lesions.ENB is an effective, minimally invasive method for the diagnosis of pulmonary nodules previously deemed unreachable by conventional bronchoscopy in high-risk patients and harbors a low complication rate.