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Item Evaluation of post-discharge engagement for emergency department patients with opioid use history who received telehealth recovery coaching services(BMC, 2023-02-11) Watson, Dennis P.; Phalen, Peter; Medcalf, Spencer; Messmer, Sarah; McGuire, Alan; Social and Behavioral Sciences, School of Public HealthBackground: In recent years, emergency departments (EDs) across the nation have implemented peer recovery coach (PRC) services to support patients who use opioids. The majority of such interventions discussed in the literature follow an in-person modality where PRCs engage patients directly at the ED bedside. However, the use of telehealth services in EDs is becoming more popular. These services connect PRCs with ED patients in real-time via secure communications technology, and very little is known about the service- and clinical-based outcomes with which they are associated. The current study sought to assess factors associated with successful post-discharge follow-up of patients with a history of opioid use who received PRC telehealth services while in the ED. Method: Data come from records for 917 patients who engaged with a telehealth PRC one or more times (1208 total engagements) at 1 of 13 EDs within the same health system. A multilevel Poisson regression model was used to assess the degree to which variables predicted successful post-discharge follow-up, defined as the number of times a PRC successfully spoke with the patient each month after ED discharge. Results: At least one follow-up was successfully completed by a PRC for 23% of enrolled patients. Significant predictors of successful follow-up included patient employment at baseline (Incidence Rate Ratio [IRR]: 2.8, CI: 2.05-3.9), living in a rural area (IRR: 1.8, CI: 1.04-3.2), PRC provision of referrals (IRR: 1.7, CI: 1.2-2.2), number of ED encounters in the previous 365 days (IRR: 0.99, CI: 0.98-0.99), and duration of the initial PRC telehealth interaction (IRR: 0.87, CI: 0.85-0.88). Conclusion: Given that relationship development is a key tool in the PRC profession, understanding successful follow-up associated with telehealth engagement has unique importance. The results have potential utility for planning and implementing peer telehealth services in EDs and other locations, which is needed for the development of the PRC profession and the likely expansion of peer telehealth services.Item Impact of Enhanced Recovery After Surgery pathway for cesarean delivery on postoperative pain(Elsevier, 2023-01-29) Grasch, Jennifer L.; Rojas, Jennymar C.; Sharifi, Mitra; McLaughlin, Megan M.; Bhamidipalli, Surya S.; Haas, David M.; Obstetrics and Gynecology, School of MedicineBackground: Enhanced Recovery After Surgery pathways provide evidence-based recommendations to optimize perioperative care. Objective: This study aimed to holistically investigate the effect of implementing an Enhanced Recovery After Surgery pathway for all cesarean deliveries on postoperative pain experience. Study design: This was a prepost study comparing subjective and objective measures of postoperative pain before and after the implementation of an Enhanced Recovery After Surgery pathway for cesarean delivery. The Enhanced Recovery After Surgery pathway was developed by a multidisciplinary team and included preoperative, intraoperative, and postoperative components, with emphasis on preoperative preparation, hemodynamic optimization, early mobilization, and multimodal analgesia. All individuals undergoing cesarean delivery, whether scheduled, urgent, or emergent, were included. Demographic, delivery, and inpatient pain management data were obtained through medical record review. Of note, 2 weeks after discharge, patients were surveyed about their delivery experience, analgesic usage, and complications. The primary outcome was inpatient opioid use. Results: The study included 128 individuals, 56 in the preimplementation cohort and 72 in the Enhanced Recovery After Surgery cohort. Baseline characteristics between the 2 groups were similar. The survey response rate was 73% (94/128). Opioid use in the first 48 hours postoperatively was significantly lower in the Enhanced Recovery After Surgery group than the preimplementation group (9.4 vs 21.4 morphine milligram equivalents 0-24 hours after delivery [P<.001]; 14.1 vs 25.4 morphine milligram equivalents 24-48 hours after delivery [P<.001]) with no increase in either average or maximum postoperative pain scores. Individuals in the Enhanced Recovery After Surgery group used fewer opioid pills after discharge (10 vs 20; P<.001). Patient satisfaction and complication rates did not change after the implementation of an Enhanced Recovery After Surgery pathway. Conclusion: The implementation of an Enhanced Recovery After Surgery pathway for all cesarean deliveries decreased both inpatient and outpatient postpartum opioid use without increasing pain scores or decreasing patient satisfaction.Item Intravenous Lidocaine Infusion for the Management of Early Postoperative Pain: A Comprehensive Review of Controlled Trials(MedWorks Media, 2020-10-15) Chu, Robert; Umukoro, Nelly; Greer, Tiashi; Roberts, Jacob; Adekoya, Peju; Odonkor, Charles A.; Hagedorn, Jonathan M.; Olatoye, Dare; Urits, Ivan; Orhurhu, Mariam Salisu; Umukoro, Peter; Viswanath, Omar; Hasoon, Jamal; Kaye, Alan D.; Orhurhu, Vwaire; Medicine, School of MedicinePreviously used as anti-arrhythmic, intravenous lidocaine infusion is becoming popular for use in management of acute pain. There is still much to be understood about its pharmacokinetics and pharmacodynamics, especially with regard to optimal dosing to avoid side effects. In this article, we selected and reviewed randomized controlled trials to summarize the pharmacokinetics, antinociceptive effects, anti-hyperalgesic effects, anti-inflammatory effects, side effects, and role of intravenous lidocaine in the management of early postoperative pain. The mechanisms of action of lidocaine are still unclear but there are many theories postulated. Optimal dosing of lidocaine is not known but general consensus indicates that a loading dose of 1-2 mg/kg, followed by 1-2 mg/kg/hr continuous infusion during early postoperative pain control while recovering from anesthesia to achieve therapeutic levels of 0.5-5 mcg/kg clearly improves analgesia in the immediate postoperative period. Although lidocaine was initially studied and proven to have clear analgesic effects following laparoscopic and open abdominal surgeries, it has now been shown to be applicable in different clinical settings perioperatively including following spinal, breast, ENT and other surgeries. It is generally safe, with hypotension, headache and vomiting being the more common side effects. Serious adverse effects include cardiovascular block and arrhythmias, neuro-excitability and hypersensitivity, although the frequency of these are not known.Item Placental cytochrome P450 methylomes in infants exposed to prenatal opioids: exploring the effects of neonatal opioid withdrawal syndrome on health horizons(Frontiers Media, 2024-01-04) Radhakrishna, Uppala; Sadhasivam, Senthilkumar; Radhakrishnan, Rupa; Forray, Ariadna; Muvvala, Srinivas B.; Metpally, Raghu P.; Patel, Saumya; Rawal, Rakesh M.; Vishweswaraiah, Sangeetha; Bahado-Singh, Ray O.; Nath, Swapan K.; Radiology and Imaging Sciences, School of MedicineBackground: Neonatal opioid withdrawal syndrome (NOWS), arises due to increased opioid use during pregnancy. Cytochrome P450 (CYP) enzymes play a pivotal role in metabolizing a wide range of substances in the human body, including opioids, other drugs, toxins, and endogenous compounds. The association between CYP gene methylation and opioid effects is unexplored and it could offer promising insights. Objective: To investigate the impact of prenatal opioid exposure on disrupted CYPs in infants and their anticipated long-term clinical implications. Study Design: DNA methylation levels of CYP genes were analyzed in a cohort of 96 placental tissues using Illumina Infinium MethylationEPIC (850 k) BeadChips. This involved three groups of placental tissues: 32 from mothers with infants exposed to opioids prenatally requiring pharmacologic treatment for NOWS, 32 from mothers with prenatally opioid-exposed infants not needing NOWS treatment, and 32 from unexposed control mothers. Results: The study identified 20 significantly differentially methylated CpG sites associated with 17 distinct CYP genes, with 14 CpGs showing reduced methylation across 14 genes (CYP19A1, CYP1A2, CYP4V2, CYP1B1, CYP24A1, CYP26B1, CYP26C1, CYP2C18, CYP2C9, CYP2U1, CYP39A1, CYP2R1, CYP4Z1, CYP2D7P1 and), while 8 exhibited hypermethylation (CYP51A1, CYP26B1, CYP2R1, CYP2U1, CYP4X1, CYP1A2, CYP2W1, and CYP4V2). Genes such as CYP1A2, CYP26B1, CYP2R1, CYP2U1, and CYP4V2 exhibited both increased and decreased methylation. These genes are crucial for metabolizing eicosanoids, fatty acids, drugs, and diverse substances. Conclusion: The study identified profound methylation changes in multiple CYP genes in the placental tissues relevant to NOWS. This suggests that disruption of DNA methylation patterns in CYP transcripts might play a role in NOWS and may serve as valuable biomarkers, suggesting a future pathway for personalized treatment. Further research is needed to confirm these findings and explore their potential for diagnosis and treatment.Item Prenatal opioid exposure significantly impacts placental protein kinase C (PKC) and drug transporters, leading to drug resistance and neonatal opioid withdrawal syndrome(Frontiers Media, 2024-08-19) Radhakrishna, Uppala; Radhakrishnan, Rupa; Uppala, Lavanya V.; Muvvala, Srinivas B.; Prajapati, Jignesh; Rawal, Rakesh M.; Bahado-Singh, Ray O.; Sadhasivam, Senthilkumar; Radiology and Imaging Sciences, School of MedicineBackground: Neonatal Opioid Withdrawal Syndrome (NOWS) is a consequence of in-utero exposure to prenatal maternal opioids, resulting in the manifestation of symptoms like irritability, feeding problems, tremors, and withdrawal signs. Opioid use disorder (OUD) during pregnancy can profoundly impact both mother and fetus, disrupting fetal brain neurotransmission and potentially leading to long-term neurological, behavioral, and vision issues, and increased infant mortality. Drug resistance complicates OUD and NOWS treatment, with protein kinase regulation of drug transporters not fully understood. Methods: DNA methylation levels of ATP-binding cassette (ABC) and solute carrier (SLC) drug transporters, along with protein kinase C (PKC) genes, were assessed in 96 placental samples using the Illumina Infinium MethylationEPIC array (850K). Samples were collected from three distinct groups: 32 mothers with infants prenatally exposed to opioids who needed pharmacological intervention for NOWS, 32 mothers with prenatally opioid-exposed infants who did not necessitate NOWS treatment, and 32 mothers who were not exposed to opioids during pregnancy. Results: We identified 69 significantly differentially methylated SLCs, with 24 hypermethylated and 34 hypomethylated, and 11 exhibiting both types of methylation changes including SLC13A3, SLC15A2, SLC16A11, SLC16A3, SLC19A2, and SLC26A1. We identified methylation changes in 11 ABC drug transporters (ABCA1, ABCA12, ABCA2, ABCB10, ABCB5, ABCC12, ABCC2, ABCC9, ABCE1, ABCC7, ABCB3): 3 showed hypermethylation, 3 hypomethylation, and 5 exhibited both. Additionally, 7 PKC family genes (PRKCQ, PRKAA1, PRKCA, PRKCB, PRKCH, PRKCI, and PRKCZ) showed methylation changes. These genes are associated with 13 pathways involved in NOWS, including ABC transporters, bile secretion, pancreatic secretion, insulin resistance, glutamatergic synapse, and gastric acid secretion. Conclusion: We report epigenetic changes in PKC-related regulation of drug transporters, which could improve our understanding of clinical outcomes like drug resistance, pharmacokinetics, drug-drug interactions, and drug toxicity, leading to maternal relapse and severe NOWS. Novel drugs targeting PKC pathways and transporters may improve treatment outcomes for OUD in pregnancy and NOWS.Item Prescriptions of opioid-containing drugs in patients with chronic cough(Sage, 2024) Weiner, Michael; Liu, Ziyue; Schelfhout, Jonathan; Dexter, Paul; Roberts, Anna R.; Griffith, Ashley; Bali, Vishal; Weaver, Jessica; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public HealthBackground: Chronic cough (CC) affects about 10% of adults, but opioid use in CC is not well understood. Objectives: To determine the use of opioid-containing cough suppressant (OCCS) prescriptions in patients with CC using electronic health records. Design: Retrospective cohort study. Methods: Through retrospective analysis of Midwestern U.S. electronic health records, diagnoses, prescriptions, and natural language processing identified CC - at least three medical encounters with cough, with 56-120 days between first and last encounter - and a 'non-chronic cohort'. Student's t-test, Pearson's chi-square, and zero-inflated Poisson models were used. Results: About 20% of 23,210 patients with CC were prescribed OCCS; odds of an OCCS prescription were twice as great in CC. In CC, OCCS drugs were ordered in 38% with Medicaid insurance and 15% with commercial insurance. Conclusion: Findings identify an important role for opioids in CC, and opportunity to learn more about the drugs' effectiveness.Item Prevention of Opioid Use and Disorder Among Youth Involved in the Legal System: Innovation and Implementation of Four Studies Funded by the NIDA HEAL Initiative(Springer, 2023) Ahrens, Kym; Blackburn, Natalie; Aalsma, Matthew; Haggerty, Kevin; Kelleher, Kelly; Knight, Danica K.; Joseph, Elizabeth; Mulford, Carrie; Ryle, Ted; Tolou-Shams, Marina; Pediatrics, School of MedicineYouth involved in the legal system (YILS) experience rates of opioid and substance use disorders (OUD/SUDs) and overdose that is well above those in the general population. Despite the dire need, and the existing programs that focus on treatment of these problems in YILS, research on opioid initiation, and OUD prevention, including feasibility and sustainability, are severely limited. We present four studies testing interventions that, while not necessarily novel as SUD treatments, test novel structural and interpersonal strategies to prevent opioid initiation/OUD precursors: (1) ADAPT (Clinical Trial No. NCT04499079) provides real-time feedback using community-based treatment information system data to create a more effective mental health and SUD treatment cascade to prevent opioid use; (2) HOME (Clinical Trial No. NCT04135703) provides youth experiencing homelessness, including YILS, with direct access to shelter in independent living without prerequisites as an opioid initiation prevention strategy; (3) LeSA (Clinical Trial No. NCT04678960) uses the Trust-Based Relational Intervention® to equip YILS and their caregivers with self-regulatory and communication skills during the transition from secure confinement to reduce opioid initiation/re-initiation; and (4) POST (Clinical Trial No. NCT04901312) tests two interventions integrating interpersonal/drinking and drug refusal skills, case management, and goal setting among YILS in transitioning out of secure detention as opioid initiation prevention strategies. We discuss early implementation barriers and facilitators, including complexities of prevention research with YILS and adaptations due to COVID-19. We conclude by describing anticipated end products, including implementation of effective prevention interventions and integration of data from multiple projects to address larger, multi-site research questions.Item The Concordance of Electronic Health Record Diagnoses and Substance use Self-Reports Among Reproductive Aged Women Enrolled in a Community-Based Addiction Reduction Program(Sage, 2024) Campbell, Angela G.; Naz, Saman; Gharbi, Sami; Chambers, Joanna; Denne, Scott; Litzelman, Debra K.; Wiehe, Sarah E.; Pediatrics, School of MedicineSubstance use disorders among reproductive aged women are a major public health issue. There is little work investigating the validity and reliability of electronic health record (EHR) data for measuring substance use in this population. This study examined the concordance of self-reported substance use with clinical diagnoses of substance use, substance abuse and substance use disorder in EHR data. Reproductive age women enrolled in the Community-Based Addiction Reduction (CARE) program were interviewed by peer recovery coaches (PRC) at enrollment. That survey data was linked with EHR data (n = 102). Concordance between self-reported substance use and clinical diagnoses in the EHR was examined for opioids, cannabis/THC, and cocaine. Cohen's kappa, sensitivity, and specificity were calculated. The survey captured a higher number of women who use substances compared to the EHR. The concordance of self-report with EHR diagnosis varied by substance and was higher for opioids (17.6%) relative to cannabis/THC (8.8%), and cocaine (3.0%). Additionally, opioids had higher sensitivity (46.2%) and lower specificity (76.2%) relative to cannabis/THC and cocaine. Survey data collected by PRCs captured more substance use than EHRs, suggesting that EHRs underestimate substance use prevalence. The higher sensitivity and lower specificity of opioids was due to a larger number of women who had a diagnosis of opioid use in the EHR who did not self-report opioid use in the self-report survey relative to cannabis/THC and cocaine. Opioid self-report and diagnosis may be influenced by research setting, question wording, or receipt of medication for opioid use disorder.