Health service utilization, substance use treatment response, and death in patients with opioid use disorder and comorbid hepatitis C findings from prospective cohort study with administrative database linkage.

BACKGROUND: Among patients with opioid use disorder (OUD), high rates of overdose and death have been reported in subgroups with Hepatitis C Virus (HCV). Evidence on the comorbid effect of HCV on clinical and substance use trajectories has been limited by small sample sizes, short follow-up, and heavy reliance on administrative data which lacks granularity on important prognostic factors. Additionally, few studies include populations on substance use treatment. AIM: To establish the impact of HCV exposure (antibody positivity) on health care utilization patterns, substance use treatment response, and death in a cohort of patients with OUD on opioid agonist therapy (OAT). METHODS: This multi-center prospective cohort study recruited adult patients with OUD on OAT from 57 substance use treatment centers in Ontario, Canada. The study collected substance use outcomes, and classified patients with ≥50 % positive opioid urine screens over one year of follow-up as having poor treatment response. Additional data obtained via linkage with ICES administrative databases evaluated the relationship between HCV status, healthcare service utilization, and death over 3 years of follow-up. Multiple logistic regression models established the adjusted impact of HCV on various outcomes. RESULTS: Among recruited participants (n = 3430), 44.10 % were female with a mean age of 38.64 years (Standard deviation: 10.96). HCV was prevalent in 10.6 % of the cohort (n = 365). Methadone was used most often (83.9 %, n = 2876), followed by sublingual buprenorphine (16.2 %, n = 554). Over the three-year follow-up, 5.3 % of patients died (n = 181). Unadjusted results reveal rates of hospitalization (all-cause, mental-health related, critical care) and emergency department visits (mental health-related), were significantly higher among HCV patients. Associations diminished in adjusted models. Active injection drug use exhibited the highest predictive risk for all outcomes. CONCLUSION: A high degree of acute physical and mental illness and its resulting health service utilization burden is concentrated among patients with OUD and comorbid HCV. Future research should explore the role for targeted interventions and how best to implement integrated healthcare models to better address the complex health needs of HCV populations who inject drugs.

Opioid prescription following radical orchiectomy associated with new persistent opioid use.

INTRODUCTION: Opioid dependence represents a public health crisis and can be observed after outpatient urologic procedures. The purpose of this study was to evaluate the risk of persistent opioid usage after radical orchiectomy for testicular cancer. MATERIALS AND METHODS: The TriNetX Research network database was queried for men between 15 and 45 years undergoing radical orchiectomy for a diagnosis of testicular cancer. All patients with N+ or M+ disease, prior opioid use, and patients who underwent chemotherapy, radiotherapy, or retroperitoneal lymph node dissection were excluded. Patients were stratified whether they were prescribed opioids or not at time of orchiectomy. The incidence of new, persistent opioid use, defined as a prescription for opioids between 3 and 15 months after orchiectomy, was evaluated. RESULTS: A total of 2,911 men underwent radical orchiectomy for testicular cancer, of which 89.8% were prescribed opioids at time of orchiectomy. After propensity score matching for age, race, and history of psychiatric diagnosis, 592 patients were included (296 received opioids, 296 did not). Overall, 0% of patients who did not receive postoperative opioids developed new persistent opioid use, whereas 10.5% of patients who received postoperative opioids developed new persistent opioid use. Patients prescribed postoperative opioids for orchiectomy had statistically higher risk difference of developing new persistent opioid use (Risk Difference: 10.5%; 95% CI: 7.0-14.0; Z: 5.7; P < 0.01). CONCLUSIONS: Postoperative opioid prescription following radical orchiectomy is significantly associated with developing new persistent opioid use, with 1 in 10 young men who received postoperative opioids obtaining a new prescription for opioids well beyond the postoperative period. Future efforts should emphasize nonopioid pathways for pain control following this generally minor procedure.

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

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

Use and misuse of psychoactive medicines: a descriptive cross-sectional study in a densely populated region of Portugal.

Introduction: Although psychoactive medicines (PMed) are needed in several psychiatric conditions, their use and misuse bear risks. We aimed at estimating the prevalence of PMed use and misuse. Methods: Data on all PMed prescribed in 2017 and dispensed in community pharmacies of the Lisbon and Tagus Valley region of Portugal (ARSLVT) were extracted from ARSLVT medicines' dispensing database. For 21 PMed among prescription opioids, benzodiazepines and z-drugs (BZDR), antidepressants (AD) and anticonvulsants (AC), we estimated the number of users of each PMed, and assessed PMed misuse by a set of proxy indicators for studying this practice: chronic use (use of ≥180 DDD during the study period) of PMed intended for short-term treatments, concomitant use of several PMed, in particular if involving long-term (≥ 30 days) opioid analgesic (OA) use, and doctor shopping (patients consulting several physicians in order to have access to a quantity higher than intended by each prescriber). Data were analysed using descriptive statistics and hypothesis testing, and multivariate logistic regression was used to explore potential factors affecting long-term concomitant treatment of chronic OA with other PMed. Results: PMed use prevalence was 21.7%: 6.6% for OA, 12.7% for benzodiazepines (BZD), 5.3% for AD and 2.8% for AC. BZDR were mainly prescribed in primary care and OA in hospital outpatients. Chronic use of PMed was observed in 25%, especially with sertraline and buprenorphine for opioid use disorder (long-term treatment), and lorazepam (short-term treatment). About 56.6% of OA chronic users were long-term concurrent users with other PMed, mainly BZDR. Risk of abuse was low for BZDR, whilst four opioids had meaningful doctor shopping indicators - fentanyl, opioid use disorder buprenorphine, morphine and hydromorphone. Conclusions: BZD are the main PMed used in ARSLVT, often chronically, especially lorazepam. Prevalence of OA use is low, although with higher risk of misuse than BZDR. Concomitant use of several PMed is frequent.

Heroin Overdose Complicated by Compartment Syndrome, Rhabdomyolysis, and Acute Renal Failure.

The opioid-abuse epidemic is a problem that continues to persist world-wide. As such, appropriately evaluating and treating such patients is crucial, especially when considering the various complications that may arise. In rare cases, opioid overdoses can be complicated by compartment syndrome, rhabdomyolysis, and acute renal failure. All three of these complications can result in life threatening emergencies. We present a case of a 38-year-old male who was brought to the emergency department after reportedly being found lying on the ground for an unknown period of time from suspected heroin overdose. He was initially treated with 2 milligrams (mg) of intramuscular naloxone en route via emergency medical services with appropriate response. Shortly after arrival to the emergency department, the patient complained of severe right lower extremity pain, paresthesia and paralysis. Patient developed acute lower extremity compartment syndrome that was further complicated by rhabdomyolysis and acute renal failure. While emergency medicine physicians are familiar with the common complications of heroin overdose including mental status changes, respiratory depression and gastrointestinal symptoms, they must also be familiar with the less common ones. Notably, acute compartment syndrome. Compartment syndrome is ultimately a clinical diagnosis and warrants emergent surgical consultation. Every patient presenting to the emergency department warrants a complete, thorough physical examination to evaluate for any and all life-threatening conditions, regardless of the presenting complaint.

Bystander-application of a novel nasal swab optimized for drug delivery is safe and non-traumatic for the general population.

OBJECTIVE: The PN Naloxone Nasal Swab (Pocket Naloxone Corp., Bethesda, MD) is a swab optimized for drug delivery and intended for use by non-medical personnel for the emergency treatment of opioid overdose. The aim of this study (PNC-20-003) is to determine the safety of this nasal swab in a real-world environment. METHODS: This was a single-institution, quantitative-qualitative prospective trial performed at an outpatient clinic. Patients with normal or abnormal nasal structure were recruited. A non-medically trained individual placed the nasal (soaked in fluorescein dye) on each side of the patient's nose. Endoscopy with recording was performed before and after swab placement. An independent reviewer rated degree of staining, mucosal bleeding, and trauma at nasal subsites. RESULTS: Videos from 32 nasal cavities (16 participants) were reviewed. All cavities had high intensity staining at the septum and the inferior turbinate. No patients had staining within the middle meatus, agger nasi, or olfactory regions. In patients with normal anatomy, obstructive nasal anatomy or prior nasal surgery, all cavities had staining near the nasal septum. Only 7 cavities (22 %) had minor bleeding defined as ooze that stopped in 1-2min, and 3 (9 %) had minor trauma defined as mucosal disruption less than 5mm. There were no significant differences in comparing pre- and post-swab nasal cavity, trauma, or bleeding exams. CONCLUSIONS: These study results showed that this swab is atraumatic to the nasal mucosal membranes when administered by non-medical personnel. Analysis suggests contact with targeted sites for drug absorption regardless of anatomy.

Decreasing Opioid Addiction and Diversion Using Behavioral Economics Applied Through a Digital Engagement Solution: Protocol for a Randomized Controlled Trial.

BACKGROUND: Despite strong and growing interest in ending the ongoing opioid health crisis, there has been limited success in reducing the prevalence of opioid addiction and the number of deaths associated with opioid overdoses. Further, 1 explanation for this is that existing interventions target those who are opiate-dependent but do not prevent opioid-naïve patients from becoming addicted. OBJECTIVE: Leveraging behavioral economics at the patient level could help patients successfully use, discontinue, and dispose of their opioid medications in an acute pain setting. The primary goal of this project is to evaluate the effect of the 3 versions of the Opioid Management for You (OPY) tool on measures of opioid use relative to the standard of care by leveraging a pragmatic randomized controlled trial (RCT). METHODS: A team of researchers from the Center for Learning Health System Sciences (CLHSS) at the University of Minnesota partnered with M Health Fairview to design, build, and test the 3 versions of the OPY tool: social influence, precommitment, and testimonial version. The tool is being built using the Epic Care Companion (Epic Inc) platform and interacts with the patient through their existing MyChart (Epic Systems Corporation) personal health record account, and Epic patient portal, accessed through a phone app or the MyChart website. We have demonstrated feasibility with pilot data of the social influence version of the OPY app by targeting our pilot to a specific cohort of patients undergoing upper-extremity procedures. This study will use a group sequential RCT design to test the impact of this important health system initiative. Patients who meet OPY inclusion criteria will be stratified into low, intermediate, and high risk of opiate use based on their type of surgery. RESULTS: This study is being funded and supported by the CLHSS Rapid Prospective Evaluation and Digital Technology Innovation Programs, and M Health Fairview. Support and coordination provided by CLHSS include the structure of engagement, survey development, data collection, statistical analysis, and dissemination. The project was initially started in August 2022. The pilot was launched in February 2023 and is still running, with the data last counted in August 2023. The actual RCT is planned to start by early 2024. CONCLUSIONS: Through this RCT, we will test our hypothesis that patient opioid use and diverted prescription opioid availability can both be improved by information delivery applied through a behavioral economics lens via sending nudges directly to the opioid users through their personal health record. TRIAL REGISTRATION: ClinicalTrials.gov NCT06124079; https://clinicaltrials.gov/study/NCT06124079. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/52882.

Development and Usability Evaluation of an Opioid Management App.

We describe the development and usability evaluation of a novel patient engagement tool (OPY) in its early stage from perspectives of both experts and end-users. The tool is aimed at engaging patients in positive behaviors surrounding the use, weaning, and disposal of opioid medications in the post-surgical setting. The messaging and design of the application were created through a behavioral economics lens. Expert-based heuristic analysis and user testing were conducted and demonstrated that while patients found the tool to be easy to use and subjectively somewhat useful, additional work to enhance the user interface and features is needed in close partnership with developers and stakeholders.

Fentanyl dysregulates neuroinflammation and disrupts blood-brain barrier integrity in HIV-1 Tat transgenic mice.

Opioid overdose deaths have dramatically increased by 781% from 1999 to 2021. In the setting of HIV, opioid drug abuse exacerbates neurotoxic effects of HIV in the brain, as opioids enhance viral replication, promote neuronal dysfunction and injury, and dysregulate an already compromised inflammatory response. Despite the rise in fentanyl abuse and the close association between opioid abuse and HIV infection, the interactive comorbidity between fentanyl abuse and HIV has yet to be examined in vivo. The HIV-1 Tat-transgenic mouse model was used to understand the interactive effects between fentanyl and HIV. Tat is an essential protein produced during HIV that drives the transcription of new virions and exerts neurotoxic effects within the brain. The Tat-transgenic mouse model uses a glial fibrillary acidic protein (GFAP)-driven tetracycline promoter which limits Tat production to the brain and this model is well used for examining mechanisms related to neuroHIV. After 7 days of fentanyl exposure, brains were harvested. Tight junction proteins, the vascular cell adhesion molecule, and platelet-derived growth factor receptor-ß were measured to examine the integrity of the blood brain barrier. The immune response was assessed using a mouse-specific multiplex chemokine assay. For the first time in vivo, we demonstrate that fentanyl by itself can severely disrupt the blood-brain barrier and dysregulate the immune response. In addition, we reveal associations between inflammatory markers and tight junction proteins at the blood-brain barrier.

Identifying patients with opioid use disorder using International Classification of Diseases (ICD) codes: Challenges and opportunities.

BACKGROUND AND AIMS: International Classification of Diseases (ICD) diagnosis codes are often used in research to identify patients with opioid use disorder (OUD), but their accuracy for this purpose is not fully evaluated. This study describes application of ICD-10 diagnosis codes for opioid use, dependence and abuse from an electronic health record (EHR) data extraction using data from the clinics' OUD patient registries and clinician/staff EHR entries. DESIGN: Cross-sectional observational study. SETTING: Four rural primary care clinics in Washington and Idaho, USA. PARTICIPANTS: 307 patients. MEASUREMENTS: This study used three data sources from each clinic: (1) a limited dataset extracted from the EHR, (2) a clinic-based registry of patients with OUD and (3) the clinician/staff interface of the EHR (e.g. progress notes, problem list). Data source one included records with six commonly applied ICD-10 codes for opioid use, dependence and abuse: F11.10 (opioid abuse, uncomplicated), F11.20 (opioid dependence, uncomplicated), F11.21 (opioid dependence, in remission), F11.23 (opioid dependence with withdrawal), F11.90 (opioid use, unspecified, uncomplicated) and F11.99 (opioid use, unspecified with unspecified opioid-induced disorder). Care coordinators used data sources two and three to categorize each patient identified in data source one: (1) confirmed OUD diagnosis, (2) may have OUD but no confirmed OUD diagnosis, (3) chronic pain with no evidence of OUD and (4) no evidence for OUD or chronic pain. FINDINGS: F11.10, F11.21 and F11.99 were applied most frequently to patients who had clinical diagnoses of OUD (64%, 89% and 79%, respectively). F11.20, F11.23 and F11.90 were applied to patients who had a diagnostic mix of OUD and chronic pain without OUD. The four clinics applied codes inconsistently. CONCLUSIONS: Lack of uniform application of ICD diagnosis codes make it challenging to use diagnosis code data from EHR to identify a research population of persons with opioid use disorder.

OralOpioids: Harnessing R Programming and Data Science to Combat Opioid Misuse.

Aims: This study aims to introduce the OralOpioids R package, a novel research tool for the in-depth study and analysis of opioid prescriptions in Canada, which reports a significant per-capita pharmaceutical opioid consumption. Methods: The OralOpioids R package employs data from Health Canada's Drug Product Database (DPD), focusing on authorized oral opioids. It systematically filters drug identification numbers (DINs) by narcotic schedules and administration routes. Moreover, it calculates the morphine equivalent dose (MED) for each DIN using the CDC table. Core functions include MED calculation for specific drugs, brand name retrieval, opioid content extraction, and unit computations based on Canadian MED guidelines. Results: When juxtaposed against renowned opioid calculators such as MDCalc, Oregon Pain, and Ohio Pain, the OralOpioids package exhibited a near-perfect correlation, with R-squared values consistently at 0.99. Conclusions: The OralOpioids package, distinctively tailored for research, marks a significant stride in understanding and monitoring Canada's opioid milieu. By encompassing data on discontinued opioids, it fosters a nuanced comprehension of the opioid panorama, enabling historical insight and post-marketing watchfulness. Primarily targeting researchers, its scope extends to healthcare providers, insurers, and administrative boards, all of whom can leverage its potent capabilities for informed decision-making. Although currently centered on Canadian opioids, its flexible design is primed for future expansion, potentially capturing a global audience and catalyzing efforts against the opioid crisis.

Opioid prescription and opioid disorders in burns: A large database analysis from 1990 to 2019.

BACKGROUND: Opioids remain crucial in the management of burn pain. A comprehensive analysis of opioid use in burns and their complications has not been investigated. METHODS: Data were collected from TriNetX, a large multicenter database with de-identified patient information. The population included patients prescribed opioids on or following burn injury from January 1st, 1990, to December 31st, 2019. Opioid prescription use was analyzed after cohort stratification by decades: 1990-1999, 2000-2009, and 2010-2019. Outcomes for opioid-related disorders, opioid dependence, opioid abuse, intentional self-harm, and mental and behavioral disorders from psychoactive substance use were investigated. RESULTS: Hydrocodone was the most frequently prescribed opioid in 1990-1999 and 2000-2009, with oxycodone taking the lead in 2010-2019 (p < 0.0001). During 1990-1999, patients had a decreased risk of recorded opioid-related disorders (RR=0.52), opioid dependence (RR=0.46), opioid abuse (RR=0.55), mental and behavioral disorders (RR=0.88), and intentional self-harm (RR=0.37) when compared to 2000-2009. A comparison of the 2000-2009-2010-2019 cohorts showed an increased risk of recorded opioid-related disorders (RR= 1.91), opioid dependence (RR=1.56), opioid abuse (RR=1.67), mental and behavioral disorders (RR =1.73), and intentional self-harm (RR=2.02). CONCLUSIONS: The risk of opioid-related disorders has nearly doubled since the year 2000 warranting precautions when prescribing pain medications to burn patients.

Whole-Body Vibration Prevents Neuronal, Neurochemical, and Behavioral Effects of Morphine Withdrawal in a Rat Model.

Peripheral mechanoreceptor-based treatments such as acupuncture and chiropractic manipulation have shown success in modulating the mesolimbic dopamine (DA) system originating in the ventral tegmental area (VTA) of the midbrain and projecting to the nucleus accumbens (NAc) of the striatum. We have previously shown that mechanoreceptor activation via whole-body vibration (WBV) ameliorates neuronal and behavioral effects of chronic ethanol exposure. In this study, we employ a similar paradigm to assess the efficacy of WBV as a preventative measure of neuronal and behavioral effects of morphine withdrawal in a Wistar rat model. We demonstrate that concurrent administration of WBV at 80 Hz with morphine over a 5-day period significantly reduced adaptations in VTA GABA neuronal activity and NAc DA release and modulated expression of δ-opioid receptors (DORs) on NAc cholinergic interneurons (CINs) during withdrawal. We also observed a reduction in behavior typically associated with opioid withdrawal. WBV represents a promising adjunct to current intervention for opioid use disorder (OUD) and should be examined translationally in humans.

Perioperative Challenges of Heroin Addiction: A Case Report of Opioid-Free Anesthesia in Tongue Carcinoma Excision With Free-Flap Reconstruction.

Anesthesia for major head and neck surgery is historically heavily reliant on opioids with deleterious consequences. We reported a case of a patient with a history of heroin abuse submitted to a tongue carcinoma excision, followed by free-flap reconstruction under opioid-free anesthesia. We used a propofol total intravenous anesthesia and perfusions of ketamine, dexmedetomidine, lidocaine, and magnesium sulfate for analgesia, complemented by boluses of dexamethasone, acetaminophen, parecoxib, and metamizole. Hemodynamic needs of the procedure were addressed by titrating perfusions of sodium nitroprusside or dobutamine. The patient was weaned from the ventilator at the end of the surgery. Surgical outcomes were achieved and opioid-free analgesia allowed early reestablishment of bodily functions without compromise of adequate pain control. Anesthesia protocols for free-flap surgery still lack scientific evidence, especially in the context of substance abuse: opioid-sparing approaches seem a viable option, which requires further studies and familiarity by health care professionals.

Opioid abuse and SIV infection in non-human primates.

Human immunodeficiency virus (HIV) and drug abuse are intertwined epidemics, leading to compromised adherence to combined antiretroviral therapy (cART) and exacerbation of NeuroHIV. As opioid abuse causes increased viral replication and load, leading to a further compromised immune system in people living with HIV (PLWH), it is paramount to address this comorbidity to reduce the NeuroHIV pathogenesis. Non-human primates are well-suited models to study mechanisms involved in HIV neuropathogenesis and provide a better understanding of the underlying mechanisms involved in the comorbidity of HIV and drug abuse, leading to the development of more effective treatments for PLWH. Additionally, using broader behavioral tests in these models can mimic mild NeuroHIV and aid in studying other neurocognitive diseases without encephalitis. The simian immunodeficiency virus (SIV)-infected rhesus macaque model is instrumental in studying the effects of opioid abuse on PLWH due to its similarity to HIV infection. The review highlights the importance of using non-human primate models to study the comorbidity of opioid abuse and HIV infection. It also emphasizes the need to consider modifiable risk factors such as gut homeostasis and pulmonary pathogenesis associated with SIV infection and opioid abuse in this model. Moreover, the review suggests that these non-human primate models can also be used in developing effective treatment strategies for NeuroHIV and opioid addiction. Therefore, non-human primate models can significantly contribute to understanding the complex interplay between HIV infection, opioid abuse, and associated comorbidities.

Effects of Roy's Adaptation Model on Quality of Life in People with Opioid Abuse under Methadone Maintenance Treatment: A Randomized Trial.

Background: Opioid abuse is one of the most obvious problems in today's world and directly affects individuals' quality of life. The present study aimed to investigate the effects of Roy's adaptation model on the quality of life in people with opioid abuse under methadone maintenance treatment. Methods: This randomized trial study was conducted in 2021 on 72 patients with opioid abuse under methadone maintenance treatment at the Center for Addiction Harm Reduction in Isfahan. The samples were randomly allocated into intervention (n=36) and control groups (n=36) based on the table of random numbers by computer. The intervention was conducted by implementing Roy's adaptation model in the intervention group. To analyze the data, paired t-test, independent sample t-test, chi-square test, and analysis of covariance were used. Results: The mean ± standard deviation of the quality of life score in the intervention group (28.96±4.79) was significantly different than before the intervention (24.02±6.09) (P<0.001). At the same time, it was not significantly different in the control group. The mean ± standard deviation of the quality of life score in the intervention group (24.02±6.09) was not significantly different from the control group (20.55±8.53) before the intervention. Conclusion: Roy's adaptation model had positive effects on the quality of life score in patients with opioid abuse. On the other hand, patients' quality of life indicates the effectiveness of methadone maintenance treatment. Therefore, it is suggested to use this model in nursing care programs.

Fentanyl in an Infant: Taking Our Breath Away.

Pediatric respiratory failure carries a wide differential diagnosis. Toxic ingestion should remain on the differential even at very young ages. There have been increasing reports of fentanyl overdoses among adults; however, this should be considered for accidental pediatric ingestion, especially considering its high potential for mortality. A nine-month-old female presented to the pediatric emergency department with respiratory failure. The patient was noted to be bradypneic with miotic pupils, and therefore, naloxone was given intravenously (IV) with a positive response. The patient required numerous boluses of intravenous naloxone, which ultimately saved her from intubation. The patient's laboratory results were later positive for fentanyl and cocaine. Fentanyl ingestion has a high mortality rate, especially in pediatrics. With increasing fentanyl use, there is a potential for exposure due to not only child abuse and intentional toxicity but also exploratory ingestions.