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Item A national study of clinical discussions about cannabis use among Veteran patients prescribed opioids(Springer Nature, 2024-03-16) Zaman, Tauheed; Bravata, Dawn M.; Byers, Amy; Krebs, Erin; Leonard, Samuel; Austin, Charles; Sandbrink, Friedhelm; Hasin, Deborah S.; Keyhani, Salomeh; Medicine, School of MedicineBackground: The Veterans Health Administration tracks urine drug tests (UDTs) among patients on long-term opioid therapy (LTOT) and recommends discussing the health effects of cannabis use. Objective: To determine the occurrence of cannabis-related discussions between providers and patients on LTOT during six months following UDT positive for cannabis, and examine factors associated with documenting cannabis use. Design: We identified patients prescribed LTOT with a UDT positive for cannabis in 2019. We developed a text-processing tool to extract discussions around cannabis use from their charts. Subjects: Twelve thousand seventy patients were included. Chart review was conducted on a random sample of 1,946 patients. Main measures: The presence of a cannabis term in the chart suggesting documented cannabis use or cannabis-related discussions. Content of those discussions was extracted in a subset of patients. Logistic regression was used to examine the association between patient factors, including state of residence legal status, with documentation of cannabis use. Key results: Among the 12,070 patients, 65.8% (N = 7,948) had a cannabis term, whereas 34.1% (N = 4,122) of patients lacked a cannabis term, suggesting that no documentation of cannabis use or discussion between provider and patient took place. Among the subset of patients who had a discussion documented, 47% related to cannabis use for medical reasons, 35% related to a discussion of VA policy or legal issues, and 17% related to a discussion specific to medical risks or harm reduction strategies. In adjusted analyses, residents of states with legalized recreational cannabis were less likely to have any cannabis-related discussion compared to patients in non-legal states [OR 0.73, 95% CI 0.64-0.82]. Conclusions: One-third of LTOT patients did not have documentation of cannabis use in the chart in the 6 months following a positive UDT for cannabis. Discussions related to the medical risks of cannabis use or harm reduction strategies were uncommon.Item Alcohol and medication interactions(U.S. National Institute on Alcohol Abuse and Alcoholism, 1999) Weathermon, Ron; Crabb, David W.; Medicine, School of MedicineMany medications can interact with alcohol, thereby altering the metabolism or effects of alcohol and/or the medication. Some of these interactions can occur even at moderate drinking levels and result in adverse health effects for the drinker. Two types of alcohol-medication interactions exist: (1) pharmacokinetic interactions, in which alcohol interferes with the metabolism of the medication, and (2) pharmacodynamic interactions, in which alcohol enhances the effects of the medication, particularly in the central nervous system (e.g., sedation). Pharmacokinetic interactions generally occur in the liver, where both alcohol and many medications are metabolized, frequently by the same enzymes. Numerous classes of prescription medications can interact with alcohol, including antibiotics, antidepressants, antihistamines, barbiturates, benzodiazepines, histamine H2 receptor antagonists, muscle relaxants, nonnarcotic pain medications and anti-inflammatory agents, opioids, and warfarin. In addition, many over-the-counter and herbal medications can cause negative effects when taken with alcohol.Item Assessment, Quantification, and Management of Fracture Pain: from Animals to the Clinic(SpringerLink, 2020-10) McVeigh, Luke G.; Perugini, Anthony J.; Fehrenbacher, Jill C.; White, Fletcher A.; Kacena, Melissa A.; Orthopaedic Surgery, School of MedicinePurpose of review: Fractures are painful and disabling injuries that can occur due to trauma, especially when compounded with pathologic conditions, such as osteoporosis in older adults. It is well documented that acute pain management plays an integral role in the treatment of orthopedic patients. There is no current therapy available to completely control post-fracture pain that does not interfere with bone healing or have major adverse effects. In this review, we focus on recent advances in the understanding of pain behaviors post-fracture. Recent findings: We review animal models of bone fracture and the assays that have been developed to assess and quantify spontaneous and evoked pain behaviors, including the two most commonly used assays: dynamic weight bearing and von Frey testing to assess withdrawal from a cutaneous (hindpaw) stimulus. Additionally, we discuss the assessment and quantification of fracture pain in the clinical setting, including the use of numeric pain rating scales, satisfaction with pain relief, and other biopsychosocial factor measurements. We review how pain behaviors in animal models and clinical cases can change with the use of current pain management therapies. We conclude by discussing the use of pain behavioral analyses in assessing potential therapeutic treatment options for addressing acute and chronic fracture pain without compromising fracture healing. There currently is a lack of effective treatment options for fracture pain that reliably relieve pain without potentially interfering with bone healing. Continued development and verification of reliable measurements of fracture pain in both pre-clinical and clinical settings is an essential aspect of continued research into novel analgesic treatments for fracture pain.Item Clinical and Quality of Life Benefits for End-Stage Workers' Compensation Chronic Pain Claimants following H-Wave® Device Stimulation: A Retrospective Observational Study with Mean 2-Year Follow-Up(MDPI, 2023-02-01) Trinh, Alan; Williamson, Tyler K.; Han, David; Hazlewood, Jeffrey E.; Norwood, Stephen M.; Gupta, Ashim; Medicine, School of MedicinePreviously promising short-term H-Wave® device stimulation (HWDS) outcomes prompted this retrospective cohort study of the longer-term effects on legacy workers’ compensation chronic pain claimants. A detailed chart-review of 157 consecutive claimants undergoing a 30-day HWDS trial (single pain management practice) from February 2018 to November 2019 compiled data on pain, restoration of function, quality of life (QoL), and polypharmacy reduction into a summary spreadsheet for an independent statistical analysis. Non-beneficial trials in 64 (40.8%) ended HWDS use, while 19 (12.1%) trial success charts lacked adequate data for assessing critical outcomes. Of the 74 final treatment study group charts, missing data points were removed for a statistical analysis. Pain chronicity was 7.8 years with 21.6 ± 12.2 months mean follow-up. Mean pain reduction was 35%, with 89% reporting functional improvement. Opioid consumption decreased in 48.8% of users and 41.5% completely stopped; polypharmacy decreased in 36.8% and 24.4% stopped. Zero adverse events were reported and those who still worked usually continued working. An overall positive experience occurred in 66.2% (p < 0.0001), while longer chronicity portended the risk of trial or treatment failure. Positive outcomes in reducing pain, opioid/polypharmacy, and anxiety/depression, while improving function/QoL, occurred in these challenging chronic pain injury claimants.Item Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6, OPRM1, and COMT Genotypes and Select Opioid Therapy(Wiley, 2021) Crews, Kristine R.; Monte, Andrew A.; Huddart, Rachel; Caudle, Kelly E.; Kharasch, Evan D.; Gaedigk, Andrea; Dunnenberger, Henry M.; Leeder, J. Steven; Callaghan, John T.; Samer, Caroline Flora; Klein, Teri E.; Haidar, Cyrine E.; Van Driest, Sara L.; Ruano, Gualberto; Sangkuhl, Katrin; Cavallari, Larisa H.; Müller, Daniel J.; Prows, Cynthia A.; Nagy, Mohamed; Somogyi, Andrew A.; Skaar, Todd C.; Medicine, School of MedicineOpioids are mainly used to treat both acute and chronic pain. Several opioids are metabolized to some extent by CYP2D6 (codeine, tramadol, hydrocodone, oxycodone and methadone). Polymorphisms in CYP2D6 have been studied for an association with the clinical effect and safety of these drugs. Other genes which have been studied for their association with opioid clinical effect or adverse events include OPRM1 (mu receptor) and COMT (catechol-O-methyltransferase). This guideline updates and expands the 2014 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 genotype and codeine therapy and includes a summation of the evidence describing the impact of CYP2D6, OPRM1 and COMT on opioid analgesia and adverse events. We provide therapeutic recommendations for the use of CYP2D6 genotype results for prescribing codeine and tramadol and describe the limited and/or weak data for CYP2D6 and hydrocodone, oxycodone and methadone and for OPRM1 and COMT for clinical use.Item Demographics, Diagnoses, Drugs, and Adjuvants in Patients on Chronic Opioid Therapy vs. Intermittent Use in a Tertiary Pediatric Chronic Pain Clinic(MDPI, 2022-12-24) Tolley, James A.; Michel, Martha A.; Sarmiento, Elisa J.; Pediatrics, School of MedicineAnywhere from 11.6% to 20% of pediatric and adolescent patients treated for chronic pain are prescribed opioids, but little is known about these patients. The purpose of this study was to determine the characteristics of patients on chronic opioid therapy (COT) and what therapies had been utilized prior to or in conjunction with COT. The study was a retrospective chart review of all chronic pain patients seen during 2020 with those patients on COT separated for analysis. A total of 346 unique patients were seen of which 257 were female (74.3%). The average age was 15.5 years. A total of 48 patients (13.9%) were identified as being on COT with an average age of 18.1 years. Of these, 23 (47.9%) were male which was significantly more than expected. The most common reason for patients to be receiving COT was palliative (13/48), and the second most common was sickle cell anemia (10/48). Patients on COT were significantly more likely to be male, be older, and to be concurrently prescribed benzodiazepines. Concurrent opioid and benzodiazepine therapy is a risk factor for respiratory depression and overdose. Further investigation into the increased proportion of males and benzodiazepine usage in patients on COT is warranted.Item Drug–gene and drug–drug interactions associated with tramadol and codeine therapy in the INGENIOUS trial(Future Medicine, 2019-04) Fulton, Cathy R.; Zang, Yong; Desta, Zeruesenay; Rosenman, Marc B.; Holmes, Ann M.; Decker, Brian S.; Zhang, Yifei; Callaghan, John T.; Pratt, Victoria M.; Levy, Kenneth D.; Gufford, Brandon T.; Dexter, Paul R.; Skaar, Todd C.; Eadon, Michael T.; Medicine, School of MedicineBackground: Tramadol and codeine are metabolized by CYP2D6 and are subject to drug-gene and drug-drug interactions. Methods: This interim analysis examined prescribing behavior and efficacy in 102 individuals prescribed tramadol or codeine while receiving pharmaco-genotyping as part of the INGENIOUS trial (NCT02297126). Results: Within 60 days of receiving tramadol or codeine, clinicians more frequently prescribed an alternative opioid in ultrarapid and poor metabolizers (odds ratio: 19.0; 95% CI: 2.8-160.4) as compared with normal or indeterminate metabolizers (p = 0.01). After adjusting the CYP2D6 activity score for drug-drug interactions, uncontrolled pain was reported more frequently in individuals with reduced CYP2D6 activity (odds ratio: 0.50; 95% CI: 0.25-0.94). Conclusion: Phenoconversion for drug-drug and drug-gene interactions is an important consideration in pharmacogenomic implementation; drug-drug interactions may obscure the potential benefits of genotyping.Item Effectiveness and implementability of state-level naloxone access policies: Expert consensus from an online modified-Delphi process(Elsevier, 2021) Smart, Rosanna; Grant, Sean; Social and Behavioral Sciences, School of Public HealthBackground: Naloxone distribution, a key global strategy to prevent fatal opioid overdose, has been a recent target of legislation in the U.S., but there is insufficient empirical evidence from causal inference methods to identify which components of these policies successfully reduce opioid-related harms. This study aimed to examine expert consensus on the effectiveness and implementability of various state-level naloxone policies. Methods: We used the online ExpertLens platform to conduct a three-round modified-Delphi process with a purposive sample of 46 key stakeholders (advocates, healthcare providers, human/social service practitioners, policymakers, and researchers) with naloxone policy expertise. The Effectiveness Panel (n = 24) rated average effects of 15 types of policies on naloxone pharmacy distribution, opioid use disorder (OUD) prevalence, nonfatal opioid-related overdoses, and opioid-related overdose mortality. The Implementation Panel (n = 22) rated the same policies on acceptability, feasibility, affordability, and equitability. We compared ratings across policies using medians and inter-percentile ranges, with consensus measured using the RAND/UCLA Appropriateness Method Inter-Percentile Range Adjusted for Symmetry technique. Results: Experts reached consensus on all items. Except for liability protections and required provision of education or training, experts perceived all policies to generate moderate-to-large increases in naloxone pharmacy distribution. However, only three policies were expected to yield substantive decreases on fatal overdose: statewide standing/protocol order, over-the-counter supply, and statewide "free naloxone." Of these, experts rated only statewide standing/protocol orders as highly affordable and equitable, and unlikely to generate meaningful population-level effects on OUD or nonfatal opioid-related overdose. Across all policies, experts rated naloxone prescribing mandates relatively lower in acceptability, feasibility, affordability, and equitability. Conclusion: Experts believe statewide standing/protocol orders are an effective, implementable, and equitable policy for addressing opioid-related overdose mortality. While experts believe many other broad policies are effective in reducing opioid-related harms, they also believe these policies face implementation challenges related to cost and reaching vulnerable populations.Item Erratum to: Examining Fatal Opioid Overdoses in Marion County, Indiana(Springer-Verlag, 2017-04) Ray, Bradley; Quinet, Kenna; Dickinson, Timothy; Watson, Dennis P.; Ballew, Alfarena; School of Public and Environmental AffairsItem Examining Fatal Opioid Overdoses in Marion County, Indiana(Springer, 2017-04-01) Ray, Bradley; Quinet, Kenna; Dickinson, Timothy; Watson, Dennis P.; Ballew, Alfarena; School of Public and Environmental AffairsDrug-related overdoses are now the leading injury-related death in the USA, and many of these deaths are associated with illicit opioids and prescription opiate pain medication. This study uses multiple sources of data to examine accidental opioid overdoses across 6 years, 2010 through 2015, in Marion County, IN, an urban jurisdiction in the USA. The primary sources of data are toxicology reports from the county coroner, which reveal that during this period, the most commonly detected opioid substance was heroin. During the study period, 918 deaths involved heroin, and there were significant increases in accidental overdose deaths involving both heroin and fentanyl. In order to disentangle the nature and source of opioid overdose deaths, we also examine data from Indiana’s prescription drug monitoring program and the law enforcement forensic services agency. Results suggest that there have been decreases in the number of opiate prescriptions dispensed and increases in law enforcement detection of both heroin and fentanyl. Consistent with recent literature, we suggest that increased regulation of prescription opiates reduced the likelihood of overdoses from these substances, but might have also had an iatrogenic effect of increasing deaths from heroin and fentanyl. We discuss several policy implications and recommendations for Indiana.