Opioid Research Articles

Mediating effect of craving on the impact of buprenorphine/naloxone and methadone treatment on opioid use: Results from a randomized controlled trial

BackgroundThe relationship between opioid craving and opioid use is unclear. We sought to determine to what extent craving mediated the relationship between opioid agonist therapy and changes in opioid use. MethodsData came from a pragmatic, 24-week, pan-Canadian, multi-centric, open-label, randomized controlled trial comparing flexible buprenorphine/naloxone take-home doses to standard supervised methadone models of care for the treatment of prescription-type opioid use disorder. Participants were randomly allocated to buprenorphine/naloxone or methadone models of care. 270 people with prescription-type opioid use disorder were included in analyses. There were 93 women (34.4%) and 2 transgender (0.7%) participants. Most participants were white (67.4%), 45.9% reported unstable living conditions, and 44.8% had psychiatric comorbidities. Generalized linear mixed models followed by mediation analysis estimated the direct effect of treatment group on Timeline Followback-reported next-week opioid use and the indirect effect through past 24-hour opioid craving measured using the Brief Substance Craving Scale at week 2, 6, 10, 14, 18 and 22. ResultsUpon mediation analysis, the average direct effect of treatment on opioid use was 0.465 (95 % CI = 0.183 to 0.751, p < 0.001). The average causal mediated effect was 0.144 (95 % CI = 0.021 to 0.110; p < 0.001). Craving accounted for 23.6 % of the effect of treatment on opioid use (p < 0.001). ConclusionsPast 24-hour craving was associated with increased next-week opioid use; however, craving only partially mediated the effect of buprenorphine/naloxone and methadone on next-week opioid use. Research is needed to develop a comprehensive understanding of factors mediating opioid use during opioid agonist therapy.

Alcohol-Related Care Among Veterans With Unhealthy Alcohol Use: The Role of Long-Term Opioid Therapy Receipt.

Long-term opioid therapy (LTOT) is potentially dangerous among patients with unhealthy alcohol use because of possible adverse interactions. We examined receipt of alcohol-related care among patients with unhealthy alcohol use receiving LTOT and without opioid receipt. We use data collected from 2009 to 2017 in the Women Veterans Cohort Study, a national cohort of Veterans engaged in Veterans Health Administration care. We included patients who screened positive for unhealthy alcohol use (score ≥5) using the Alcohol Use Disorder Identification Consumption questionnaire. Our primary exposure was LTOT (receipt of prescribed opioids for ≥90 days) versus no opioid receipt at the time of the first positive Alcohol Use Disorder Identification Consumption. Our primary outcome was receipt of brief intervention within 14 days of positive alcohol screen. Unadjusted and 4 adjusted modified Poisson regression models assessed prevalence and relative rates (RRs) of outcomes. Among eligible veterans, 6222 of 113,628 (5.5%) received LTOT at screening. Among patients receiving LTOT, 67.5% (95% confidence interval [CI], 66.3%-68.6%) had a documented brief intervention within 14 days of positive screen, compared with 70.1% (95% CI, 69.8%-70.4%) among patients without opioid receipt (RR, 0.96; 95% CI, 0.95-0.98; P < 0.001). Within adjusted models, the rate of brief intervention among patients receiving LTOT remained lower than patients without opioid receipt. Among patients with unhealthy alcohol use, patients receiving LTOT had significantly lower rates of brief intervention receipt compared with those without opioid receipt, and they should be a focus for interventions to improve alcohol-related care and safer opioid prescribing.

Characterizing the opioidergic mechanisms of repetitive transcranial magnetic stimulation-induced analgesia: a randomized controlled trial.

Repetitive transcranial magnetic stimulation (rTMS) is a promising technology to reduce chronic pain. Investigating the mechanisms of rTMS analgesia holds the potential to improve treatment efficacy. Using a double-blind and placebo-controlled design at both stimulation and pharmacologic ends, this study investigated the opioidergic mechanisms of rTMS analgesia by abolishing and recovering analgesia in 2 separate stages across brain regions and TMS doses. A group of 45 healthy participants were equally randomized to the primary motor cortex (M1), the dorsolateral prefrontal cortex (DLPFC), and the Sham group. In each session, participants received an intravenous infusion of naloxone or saline before the first rTMS session. Participants then received a second dose of rTMS session after the drugs were metabolized at 90 minutes. M1-rTMS-induced analgesia was abolished by naloxone compared with saline and was recovered by the second rTMS run when naloxone was metabolized. In the DLPFC, double but not the first TMS session induced significant pain reduction in the saline condition, resulting in less pain compared with the naloxone condition. In addition, TMS over the M1 or DLPFC selectively increased plasma concentrations of β-endorphin or encephalin, respectively. Overall, we present causal evidence that opioidergic mechanisms are involved in both M1-induced and DLPFC-rTMS-induced analgesia; however, these are shaped by rTMS dosage and the release of different endogenous opioids.

Liver stiffness and associated risk factors among people with a history of injecting drugs: a prospective cohort study

BackgroundPersons with opioid use disorders (OUD) and persons with substance use disorders (SUD) who inject substances have a reduced life expectancy of up to 25 years compared with the general population. Chronic liver diseases are a substantial cause of this. Screening strategies based on liver stiffness measurements (LSM) may facilitate early detection, timely intervention, and treatment of liver disease. This study aims to investigate the extent of chronic liver disease measured with transient elastography and the association between LSM and various risk factors, including substance use patterns, hepatitis C virus (HCV) infection, alcohol use, body mass index, age, type 2 diabetes mellitus, and high-density lipoprotein (HDL) cholesterol among people with OUD or with SUD who inject substances.MethodsData was collected from May 2017 to March 2022 in a cohort of 676 persons from Western Norway. The cohort was recruited from two populations: Persons receiving opioid agonist therapy (OAT) (81% of the sample) or persons with SUD injecting substances but not receiving OAT. All participants were assessed at least once with transient elastography. A linear mixed model was performed to assess the impact of risk factors such as HCV infection, alcohol use, lifestyle-associated factors, and substance use on liver stiffness at baseline and over time. Baseline was defined as the time of the first liver stiffness measurement. The results are presented as coefficients (in kilopascal (kPa)) with 95% confidence intervals (CI).ResultsAt baseline, 12% (n = 83) of the study sample had LSM suggestive of advanced chronic liver disease (LSM ≥ 10 kPa). Advanced age (1.0 kPa per 10 years increments, 95% CI: 0.68;1.3), at least weekly alcohol use (1.3, 0.47;2.1), HCV infection (1.2, 0.55;1.9), low HDL cholesterol level (1.4, 0.64;2.2), and higher body mass index (0.25 per increasing unit, 0.17;0.32) were all significantly associated with higher LSM at baseline. Compared with persistent chronic HCV infection, a resolved HCV infection predicted a yearly reduction of LSM (-0.73, -1.3;-0.21) from baseline to the following liver stiffness measurement.ConclusionsMore than one-tenth of the participants in this study had LSM suggestive of advanced chronic liver disease. It underscores the need for addressing HCV infection and reducing lifestyle-related liver risk factors, such as metabolic health factors and alcohol consumption, to prevent the advancement of liver fibrosis or cirrhosis in this particular population.

Erector spinae plane block as a component of intensive care for acute pancreatitis: a prospective randomized pilot study

BACKGROUND: Analgesia is crucial in the treatment of patients with acute pancreatitis, which includes the increased use of regional analgesia. In recent years, less-invasive and safer methods of pain relief, particularly erector spinae plane block (ESP-block), has drawn attention from the anesthesiological community. However, studies on its use in acute pancreatitis are rare. OBJECTIVE: Our aim was to make a clinical evaluation of bilateral erector spinae plane block in patients with acute pancreatitis. MATERIALS AND METHODS: A pilot prospective randomized study was conducted. The patients were divided into two groups: group 1 (n=7), ESP blockade was used, and group 2 (n=12), epidural analgesia (EA) was used. The primary points were considered to be an assessment of pain syndrome intensity and the need for analgesics. Additional results were liver and kidney function, acid-base condition, inflammatory response level, and the time of onset of peristalsis. RESULTS: The decrease in pain intensity in both groups was unidirectional: after 8 h, it was 3.57±1.98 points to the NRS in group 1 and 2.91±1.97 points to the NRS in group 2, and after 24 h, it was 1.42±1.27 and 1.75±2.3 points to the NRS, respectively. No significant difference was found in pain intensity between the groups (р 0,05). The average consumption of ketorolac was 78.2±16.3 mg in group 2 — 63.28±17.23 mg for 1 patient. The average need for narcotic analgesics, that is, morphine, per patient was 22±8 mg in group 1 and 36.3±17.2 mg in group 2 (р 0,05). During the therapy, blood α-amylase, diuresis rate, creatinine level, and glomerular filtration rate did not have a significant difference between the groups, as well as pH, BE, and blood lactate levels (р 0,05). Peristalsis was noted after 12.49±19.73 h in the ESP-block group and after 16.9±21.3 h in the 2nd group (р 0,05). The ICU length of stay between the groups did not differ and was 62±3 and 62±7 h, respectively (р 0,05). CONCLUSION: Bilateral erector spinae plane block is a simple and safe method that induces analgesic effect and effect on homeostasis in acute pancreatitis, similar to epidural blockade. Further study of the role and location of erector spinae plane block in treating pain in acute pancreatitis is required.

Odevixibat: A Novel Bile Salt Inhibitor Treatment for Pruritus in Progressive Familial Intrahepatic Cholestasis.

Chronic pruritus is defined as an itch lasting greater than six weeks. It can manifest from a wide variety of etiologies, as many different substances can act as pruritogens, such as steroids, histamine, progesterone, endogenous opioids, and serotonin. In the setting of cholestatic liver disease, increased bile acids play a major role in chronic pruritus. The itching in cholestatic liver disease is worsened in intensity at night and localized frequently to the palms, soles, knees, and other pressure sites. It can be hard to manage, affecting the quality of sleep and causing irritability, poor attention, and, in some cases, depression. One such disease that results from chronic pruritus is progressive familial intrahepatic cholestasis (PFIC), a group of uncommon hereditary disorders that affects the formation of bile and its outflow from the liver. Previously, the drug ursodeoxycholic acid was used to help manage pruritus or surgical procedures, e.g., partial external biliary diversion or partial internal biliary diversion, to help control complications of the disease. This literature review will discuss three clinical studies covering the effectiveness of odevixibat in treating pruritus in patients with PFIC. Odevixibat (Bylvay) is an oral drug that has been FDA-approved to treat pruritus in patients three months of age and older with PFIC. Odevixibat prevents the reabsorption of bile salts in the intestines, resulting in decreased levels of bile salts via their excretion in stool. Several studies have determined that the drug is well tolerated and provides a nonsurgical, pharmacological treatment alternative for those with PFIC.

Abstract 2249: Clinical outcomes of discontinuing long-term opioid therapy among older cancer survivors in nursing homes

Abstract Purpose: The purpose of this study is to investigate associations of discontinuing vs continuing long-term opioid therapy (LTOT) with pain, physical function, and depressive symptoms among older cancer survivors who resided in nursing homes. Pain is prevalent and use of LTOT is common among patients with cancer, including those living in nursing homes. The Centers for Disease Control and Prevention (CDC) Guideline for Prescribing Opioids for Chronic Pain—United States recommends tapering or discontinuing LTOT for patients with chronic pain when risks outweigh the benefits of LTOT. Despite the guideline explicitly stating that its recommendation does not apply to patients with cancer, doctors including oncologists have been prescribing fewer opioid medications for older patients, raising a question regarding the benefit and risk of discontinuing LTOT for cancer survivors who depend on opioids for pain relief. Study Design: We conducted a cohort study using a 100% Medicare nursing home sample linked to the Minimum Data Set (MDS) from 2010 to 2021. Participants included older (≥65 years of age) long-term (≥2 years) residents with a diagnosis of cancer who received LTOT for ≥90 days in a 12-month nursing home stay. Residents entered the cohort on the 90th day of the latest LTOT episode. Residents who received palliative or hospice care were excluded. The key exposure was discontinuation of LTOT, defined as no opioid refills for ≥90 consecutive days in 1 year after cohort entry. The primary outcomes were pain (measured using a numerical rating scale or categorical verbal descriptor scale), physical function (9-item activities of daily living scale), and depression (Patient Health Questionnaire-9) from baseline to quarterly assessments during 1-year follow-up after the discontinuation of LTOT. Results: In total, 53,141 cancer survivors who received LTOT were identified (mean [SD] age, 82.9 [8.7] years; 39,522 [74.4%] female; 46678 [87.8] Whites), consisting of 62,387 patient observations during the 10-year study period. Of 62,387 patient observations, 51,357 residents (82.3%) continued LTOT, and 11,030 (17.6%) discontinued LTOT. Residents who discontinued (vs continued) LTOT had lower odds of worsening pain (adjusted odds ratio [AOR], 0.64, 95% CI, 0.59-0.59, P &amp;lt; .001) and depressive symptoms (AOR, 0.92 [95% CI, 0.85-0.99]; P = .033), with no difference in physical function (AOR, 0.96 [95% CI, 0.89-1.03]; P = .226) during the 1-year follow-up. Conclusion: Among older nursing home residents with cancer, discontinuing vs continuing LTOT was associated with lower odds of worsening pain and depressive symptoms. Funding source: NIH/NIA R01AG073442. Citation Format: Yu-Jung Jenny Wei, Almut G. Winterstein, Siegfried Schmidt, Roger B. Fillingim, Michael Daniels, Steven T. DeKosky, Ben Kinder, Ting-Yuan David Cheng. Clinical outcomes of discontinuing long-term opioid therapy among older cancer survivors in nursing homes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2249.

Opioids in Treatment of Refractory Dyspnea in Chronic Obstructive Pulmonary Disease: Yes, No or Maybe.

Chronic Obstructive Pulmonary Disease (COPD) is a complex condition with significant impact on prognosis, especially in advanced stages where symptom burden becomes critical. Breathlessness affects patients' quality of life, and despite various therapeutic strategies, the role of opioids in palliative care for COPD remains under investigation. The acceptance of a therapeutic trial of different types of opioids is increasing not only in end-of-life situations but also for stable COPD patients experiencing intolerable refractory breathlessness despite optimal conventional therapy. Recent clinical trials have raised questions about the overall clinical benefit of opioids in addressing breathlessness in COPD, prompting the need to clarify inconsistencies and identify specific subgroups that may benefit from opioid therapy. In the clinical setting, it is crucial to understand the attributes of patients who exhibit positive responses to opioids and what type of opioids could have a positive impact. This research paper aims to offer an update of the most recent evidence of opioid treatment in managing breathlessness among individuals with COPD with a head-to-head evaluation of the supporting and opposing proof in the medical literature.

Patients' perspectives about the role of primary healthcare providers in long-term opioid therapy: a qualitative study in Dutch primary care.

Over the past decade, long-term use of prescription opioids for chronic non-cancer pain has risen globally despite the associated risks. Most opioid users receive their first prescription in primary care. To investigate the perspective of patients who are long-term opioid users in primary care regarding the role of healthcare providers (HCPs) in their prolonged opioid use. Semi-structured interviews in Dutch primary care. We recruited patients who were long-term users of opioids for chronic non-cancer pain from seven community pharmacies in the Netherlands. In-depth, semi-structured interviews focused on patients' experiences with long-term opioid use, access to opioids, and the guidance of their HCPs (primarily their GPs and pharmacists). A directed content analysis was conducted on the transcribed interviews using NVivo. Participants (n = 25) described ways in which HCPs impacted their long-term use of opioids. These encompassed the initiation of treatment, chronic use of opioids, and discontinuation of treatment. Participants stressed the need for risk counselling during initial prescribing, ongoing medication evaluations including tapering conversations, and more support from their HCP during a tapering attempt. Patients' perspectives illustrate the important role of HCPs across the spectrum of opioid use - from initiation to tapering. The results of this study underscore the importance of clear risk counselling starting at initial prescribing, repeated medication assessments throughout treatment, addressing tapering at regular intervals, and strong support during tapering. These insights carry significant implications for clinical practice, emphasising the importance of informed and patient-centred care when it comes to opioid use for chronic non-cancer pain management.

Antineuropathic Pain Management After Orthopedic Surgery: A Systematic Review.

The opioid crisis has become a present concern in the medical field. In an effort to address these complications, antineuropathic pain medications have been considered as alternatives to prescribed opioids. This review focuses on the analgesic effects of neuromodulators, such as gabapentin, duloxetine, and pregabalin, that provide room for less dependence on narcotic analgesics following orthopedic surgery. During the database searches, 1,033 records were identified as a preliminary result. After duplicates were removed, an initial screen of each article was completed which identified records to be removed due to absence of a full-text article. Articles were excluded if they were not either prospective or retrospective, showcased an irrelevant medication (such as tricyclic antidepressants) which are not pertinent to this review, or deemed to be unrelated to the topic. Ultimately, 19 articles were selected. Three different drugs, gabapentin, pregabalin, and duloxetine, were analyzed to compile data on the effectiveness of preventing opioid overuse and addiction following hand surgery. This review identifies potential evidence that peri-operative gabapentin, pregabalin, and duloxetine administration decreases post-operative pain and lowers opioid dependency. Gabapentin, pregabalin, and duloxetine have potential to further decrease post-operative pain and lower opioid dependency. This review creates an opening for further research in hand surgery to assess an updated protocol for pain management to reduce opioid dependency.

A national study of clinical discussions about cannabis use among Veteran patients prescribed opioids

BackgroundThe 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.ObjectiveTo 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.DesignWe 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.SubjectsTwelve thousand seventy patients were included. Chart review was conducted on a random sample of 1,946 patients.Main measuresThe 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 ResultsAmong 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].ConclusionsOne-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.

The Role of Pharmacists in Opioid Addiction Management

Opioid addiction claims thousands of lives every year in the United States. The prevalence of misuse, abuse, and overdose continues to rise despite the measures and initiatives taken by the federal government and other government agencies to manage the problem. These efforts have led to a re-evaluation of the role different healthcare providers can play to ensure the problem is adequately addressed. Being one of the most accessible healthcare providers to patients under opioid therapy, pharmacists are better positioned to deal with opioid addiction. They dispense millions of opioids every year making them better positioned to screen for patients who are likely to develop an addiction problem and refer them to treatment resources before the abuse escalates to opioid use disorder (OUD). The aim of this review is to explore the role of pharmacists in opioid addiction management including prevention, screening, education, naloxone prescribing, counselling, and referral to treatment resources. The review also provides pertinent information regarding the current state of the opioid crisis in the US, including recent data on prevalence and opioid-related deaths. Exploring the role of pharmacists is instrumental in coming up with effective measures that can help in opioid addiction management. Keywords: opioids, opioid addiction management, pharmacists, opioid misuse, opioid abuse, opioid use disorder

Medicaid Insurance Predicts Increased Postoperative Care Encounters Among Patients on Long-Term Opioid Therapy.

This study examined the association between insurance type and postoperative unplanned care encounters among patients on long-term opioid therapy prior to surgery. Preoperative long-term opioid therapy is associated with unique risks and poorer outcomes following surgery. To date, the extent to which insurance coverage influences postoperative outcomes in this population remains unclear. Among individuals receiving a supply of greater than 120 total days or at least 10 opioid prescriptions in the year prior to surgery, we examined patients with Medicaid or private insurance who underwent abdominopelvic surgery from 2017 to 2021 across 70 hospitals in the state of Michigan. The primary outcome was unplanned care encounters, defined as an emergency department visit or unplanned readmission within 30 days of discharge from surgery. Multivariable logistic regression was used to assess the likelihood of acute care events with insurance type as the primary covariate of interest. Among 1212 patients on long-term opioid therapy prior to surgery, 45.6% (n = 553) had Medicaid insurance. Overall, one in eight (n=151) patients met criteria for a postoperative unplanned care encounter within 30 days. The probability of an unplanned encounter was 4.5 percentage points higher among patients with Medicaid insurance compared to private insurance (95% CI: 0.5%, 8.4%). Among patients on preoperative long-term opioid therapy, unplanned care encounters were higher among patients with Medicaid when compared to private insurance. While this is likely multifactorial, differences by insurance status may point to disparities in underlying social determinants of health and suggest the need for postoperative care pathways that address these gaps.

Improving hospital-based opioid substitution therapy (iHOST): protocol for a mixed-methods evaluation

Background Opioid substitution therapy is associated with improved health and social outcomes for people who use heroin and other illicit opioids. It is typically managed in the community and is not always continued when people are admitted to hospital. This causes opioid withdrawal, discharge against medical advice, and increased costs. We are establishing a project called iHOST (improving hospital opioid substitution therapy) to address these problems. This is an applied health research project in which we will develop and evaluate an intervention that aims to improve opioid substitution therapy in three acute hospitals in England. The intervention was developed in collaboration with stakeholders including people who use opioids, hospital staff, and other professionals who work with this group. It includes five components: (1) a card that patients can use to help hospital clinicians confirm their opioid substitution therapy, (2) a helpline for patients and staff, (3) an online training module for staff, (4) a clinical guideline for managing opioid withdrawal in hospital, and (5) ‘champion’ roles at each hospital. Methods We will do a mixed-methods study including a quasi-experimental quantitative study and a qualitative process evaluation. The primary outcomes for the quantitative study are discharge against medical advice and emergency readmission within 28 days. We will do a difference-in-difference analysis comparing changes in these outcomes for patients at iHOST sites with changes for patients at control hospitals. The process evaluation will use in-depth interviews, focus groups, and site observations with people who use opioids and staff. We will assess acceptability of the intervention, barriers and facilitators to implementation, and contextual factors impacting outcomes. Impact We anticipate that iHOST will improve care for hospital patients who use illicit opioids and/or are receiving community-based opioid substitution therapy. Depending on the results, we will promote the intervention at hospitals across the UK. Dissemination, including through publication, will inform hospital-based services for people who use drugs both in the UK and other countries.

Patterns of Socioeconomic Marginalization among People Who Use Drugs: A Gender-Stratified Repeated Measures Latent Class Analysis.

Socioeconomic factors are important correlates of drug use behaviors and health-related outcomes in people who use drugs (PWUD) residing in urban areas. However, less is known about the complex overlapping nature of socioeconomic conditions and their association with a range of individual, drug use, and health-related factors in men and women who use drugs. Data were obtained from two community-recruited prospective cohorts of PWUD. Using a gender-stratified approach, we conducted repeated measures latent class analyses (RMLCA) to identify discrete latent socioeconomic subgroups. Multivariable generalized estimating equations were then used to identify correlates of class membership. Between June 2014 and December 2018, RMLCA of 9844 observations from 1654 participants revealed five distinct patterns of socioeconomic status for both men and women. These patterns were primarily distinguished by variations in income, material and housing security, income generation activity, exposure to violence, criminal justice involvement, and police contact. Across gender, progressive increases in exposure to multiple dimensions of socioeconomic disadvantage were found to be associated with frequent use of opioids and stimulants, accessing social services, and being hepatitis C virus antibody-positive. Similar but less congruent trends across gender were observed for age, binge drug use, engagement with opioid agonist therapy, and living with HIV. Gendered patterns of multiple and overlapping dimensions of socioeconomic adversity aligned with patterns of frequent drug use and health-related concerns, highlighting priority areas for gender-inclusive, multilevel responses to mitigate health disparities and meet the diverse socioeconomic needs of urban-dwelling men and women who use drugs.

Pain Care at Home to Amplify Function: Protocol Article.

Guidelines recommend strategies to optimize opioid medication safety, including frequent reassessment of the benefits and harms of long-term opioid therapy. Prescribers, who are predominantly primary care providers (PCPs), may lack the training or resources to implement these guideline-concordant practices. Two interventions have been designed to assist PCPs and tested within the Veterans Health Administration (VHA). Telemedicine Collaborative Management (TCM) provides primarily medication management support via care manager-prescriber teams. Cooperative Pain Education and Self-Management (COPES) promotes self-management strategies for chronic pain via cognitive behavior therapy techniques. Each intervention has been shown to improve prescribing and/or patient outcomes. The added value of combining these interventions is untested. With funding and central coordination by the Integrative Management of Chronic Pain and Opioid Use Disorder for Whole Recovery (IMPOWR) Network of the National Institutes of Health Helping to End Addiction Long-term (HEAL) Initiative, we will conduct a multisite patient-level randomized hybrid II effectiveness-implementation trial within VHA to compare TCM to TCM + COPES on the primary composite outcome of pain interference and opioid safety, secondary outcomes of alcohol use, anxiety, depression, and sleep, and other consensus IMPOWR Network measures. Implementation facilitation strategies informed by interviews with healthcare providers will target site-specific needs. The impact of these strategies on TCM implementation will be assessed via established formative and summative evaluation techniques. Economic analyses will evaluate intervention cost-effectiveness.

Buprenorphine for pain management vs. chronic hydrocodone-acetaminophen therapy when comorbidities increase the risk of opioid-related side effects

A clinical decision report using: Gordon A, Callaghan D, Spink D, et al. Buprenorphine transdermal system in adults with chronic low back pain: a randomized, double-blind, placebo-controlled crossover study, followed by an open-label extension phase. Clin Ther. 2010;32(5):844-860. https://doi.org/10.1016/j.clinthera.2010.04.018 for a patient on long-term opioid therapy with high risk factors for adverse effects

Safety, Tolerability, and Dose-Limiting Toxicity of Lacosamide in Patients With Painful Chronic Pancreatitis: Protocol for a Phase 1 Clinical Trial to Determine Safety and Identify Side Effects.

Chronic abdominal pain is the hallmark symptom of chronic pancreatitis (CP), with 50% to 80% of patients seeking medical attention for pain control. Although several management options are available, outcomes are often disappointing, and opioids remain a mainstay of therapy. Opioid-induced hyperalgesia is a phenomenon resulting in dose escalation, which may occur partly because of the effects of opioids on voltage-gated sodium channels associated with pain. Preclinical observations demonstrate that the combination of an opioid and the antiseizure drug lacosamide diminishes opioid-induced hyperalgesia and improves pain control. In this phase 1 trial, we aim to determine the safety, tolerability, and dose-limiting toxicity of adding lacosamide to opioids for the treatment of painful CP and assess the feasibility of performance of a pilot study of adding lacosamide to opioid therapy in patients with CP. As an exploratory aim, we will assess the efficacy of adding lacosamide to opioid therapy in patients with painful CP. Using the Bayesian optimal interval design, we will conduct a dose-escalation trial of adding lacosamide to opioid therapy in patients with painful CP enrolled in cohorts of size 3. The initial dose will be 50 mg taken orally twice a day, followed by incremental increases to a maximum dose of 400 mg/day, with lacosamide administered for 7 days at each dose level. Adverse events will be documented according to Common Terminology Criteria for Adverse Events (version 5.0). As of December 2023, we have currently enrolled 6 participants. The minimum number of participants to be enrolled is 12 with a maximum of 24. We expect to publish the results by March 2025. This trial will test the feasibility of the study design and provide reassurance regarding the tolerability and safety of opioids in treating painful CP. It is anticipated that lacosamide will prove to be safe and well tolerated, supporting a subsequent phase 2 trial assessing the efficacy of lacosamide+opioid therapy in patients with painful CP, and that lacosamide combined with opiates will lower the opioid dose necessary for pain relief and improve the safety profile of opioid use in treating painful CP. Clinicaltrials.gov NCT05603702; https://clinicaltrials.gov/study/NCT05603702. PRR1-10.2196/50513.

Most dynorphin neurons in the zona incerta-perifornical area are active in waking relative to non-rapid-eye movement and rapid-eye movement sleep.

Dynorphin is an endogenous opiate localized in many brain regions and spinal cord, but the activity of dynorphin neurons during sleep is unknown. Dynorphin is an inhibitory neuropeptide that is coreleased with orexin, an excitatory neuropeptide. We used microendoscopy to test the hypothesis that, like orexin, the dynorphin neurons are wake-active. Dynorphin-cre mice (n = 3) were administered rAAV8-Ef1a-Con/Foff 2.0-GCaMP6M into the zona incerta-perifornical area, implanted with a GRIN lens (gradient reflective index), and electrodes to the skull that recorded sleep. One month later, a miniscope imaged calcium fluorescence in dynorphin neurons during multiple bouts of wake, non-rapid-eye movement (NREM), and rapid-eye movement (REM) sleep. Unbiased data analysis identified changes in calcium fluorescence in 64 dynorphin neurons. Most of the dynorphin neurons (72%) had the highest fluorescence during bouts of active and quiet waking compared to NREM or REM sleep; a subset (20%) were REM-max. Our results are consistent with the emerging evidence that the activity of orexin neurons can be classified as wake-max or REM-max. Since the two neuropeptides are coexpressed and coreleased, we suggest that dynorphin-cre-driven calcium sensors could increase understanding of the role of this endogenous opiate in pain and sleep.

A Systematic Review of Naldemedine and Naloxegol for the Treatment of Opioid-Induced Constipation in Cancer Patients.

Opioid-induced constipation (OIC) is a pervasive and distressing side effect of chronic opioid therapy in patients with cancer pain, significantly impacting their quality of life. Peripherally acting μ-opioid receptor antagonists (PAMORAS) were developed for treatment-resistant OIC but most studies were conducted with non-cancer patients. to discuss two oral formulations of PAMORAs, naldemedine and naloxegol, and to review available evidence of the effectiveness of these drugs for OIC in cancer patients. a comprehensive search to identify primary literature for either naldemedine or naloxegol for OIC in cancer patients. Only three prospective randomized, double-blind, placebo-controlled clinical trials for naldemedine enrolling cancer patients were identified; the results of a subgroup analysis of two of those studies and two non-interventional post marketing surveillance studies of these trials are also reported here. For naloxegol, only two randomized controlled trials were identified; both were unsuccessful in enrolling sufficient patients. An additional four prospective non-interventional observational studies with naloxegol were found that enrolled cancer patients. There were significantly higher rates of responders in the PAMORA groups than in the placebo groups. The most common side effect for both PAMORAs was diarrhea. All studies were industry-funded, and given that only three trials were randomized controlled studies, the overall quality of the studies was lacking. Naldemedine or naloxegol appeared safe and useful in the treatment of OIC in cancer patients and may improve their quality of life. Larger-scale randomized placebo-controlled studies of PAMORAs in cancer patients would strengthen existing evidence.